KR810000932B1 - Process for preparing bis-pyridinium alkane - Google Patents

Process for preparing bis-pyridinium alkane Download PDF

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KR810000932B1
KR810000932B1 KR7700427A KR770000427A KR810000932B1 KR 810000932 B1 KR810000932 B1 KR 810000932B1 KR 7700427 A KR7700427 A KR 7700427A KR 770000427 A KR770000427 A KR 770000427A KR 810000932 B1 KR810000932 B1 KR 810000932B1
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pyridinium
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pyridine
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마아론 베이리 데니스
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에이 디이 록크웃드
스터어링 드럭그 인코포레이팃트
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract

Bis-pyridinium alkanes[I,II; Y = C4-18 alkylene; R = nitro, C6-18 alkyl, C5-7 cyclo alkyl, benzyl, halogen, lower alkyl, lower alkoxy, cyano, substituted phenyl; Q = methyl, Cl; V = 0-4; A = anion; m = 1,3; n = 1,2; X = 1,2,3; (m)2 = (n)(x) , useful as fungicide, were prepd. by reacting 4-(R-amino)pyridine(III) 2 mole with double substituted alkane(IV; Z = chloro, bromo, iodo, methane sulfonyloxy, ethane sulfonyl oxy, p-toluene sulfonyl oxy) 1 mole or α,α'-double substituted xylene(v) 1 mole.

Description

비스-피리디늄 알칸의 제조방법Method for preparing bis-pyridinium alkanes

본 발명은 비스-(4-아미노-1-피리디늄)알칸류 및

Figure kpo00001
,
Figure kpo00002
'-비스-(4-아미노-1-피리디늄)크실렌류 그리고 이들의 제조방법에 관한 것이다. 상기 화하물은 박테리아, 진균 및 포진바이러스(Herpes Viruses)를 억제하는데 유용하며, 이들 화합물중 몇몇은 치구(齒垢), dental palque)의 형성을 방지하는데 유용하다.The present invention relates to bis- (4-amino-1-pyridinium) alkanes and
Figure kpo00001
,
Figure kpo00002
'-Bis- (4-amino-1-pyridinium) xylenes and methods for their preparation. These compounds are useful for inhibiting bacteria, fungi and herpes viruses, and some of these compounds are useful for preventing the formation of dental palques.

일군의 비스-(4-아미노-1-피리디늄)-알킨류는 정균효과 및 살균효과를 가진 상응하는 비스-(4-아미노-1-피페리디노)알칸류를 제조하는데 중간체로서 공지되어 있다.A group of bis- (4-amino-1-pyridinium) -alkynes are known as intermediates for preparing the corresponding bis- (4-amino-1-piperidino) alkanes having bacteriostatic and bactericidal effects. .

1, 10-비스-(4-아미노-1-피리디늄)데칸 디아이오다이드 및 1, 10-비스-(4-아세트아미노-1-피리디늄)데칸 다이오다이드는 오스틴 등(W.C. Austin et al.)에 의하여 약품 약리학회지(J. Pharm. Pharmacol) 11, 80-93면 (1959)에 기술되어 있다. 여기에 기술된 4차 암모늄 화합물의 여러가지 군중 몇몇 종류는 항아메바, 항박테리아, 항사상충(anti-filarial) 및 살(殺)트리파노조마활성을 가지고 있다고 언급되어 있으나, 상기 화합물에 대한 생물학적 데이타는 기재되어 있지 않았다.1, 10-bis- (4-amino-1-pyridinium) decane diiodide and 1,10-bis- (4-acetamino-1-pyridinium) decane diiodide are described by Austin et al. J. Pharm. Pharmacol 11, pp. 80-93 (1959). Several different classes of quaternary ammonium compounds described herein are mentioned to have anti-amoeba, antibacterial, anti-filarial, and saltripnozoma activity, but biological data for these compounds It is not described.

본 발명은 다음 구조식(I)의 비스-[4-(R-아미노)-1-피리디늄]-알칸류와 다음 구조식(II)의

Figure kpo00003
,
Figure kpo00004
'-비스-[4-(R-아미노)-1-피리디늄] 크실렌류에 관한 것이다.The present invention relates to bis- [4- (R-amino) -1-pyridinium] -alkanes of the formula (I) and the following formula (II).
Figure kpo00003
,
Figure kpo00004
'-Bis- [4- (R-amino) -1-pyridinium] xylenes.

Figure kpo00005
Figure kpo00005

상기 구조식(I)에서;In formula (I) above;

Y는 C4-C18의 알킬렌기로서, 2개의 4-(R-NH)-1-피리니디닐기를 C4-C18에 의해 분리시키며; R은 C6-C18의 알킬기, C5-C7의 사이클로알킬기, 벤질이거나, 또는 할로켄, 저급 알킬, 저급 알콕시, 니트로, 시아노 및 트리플루오로메틸로 구성된 군으로 부터 선택된 하나 또는 2개의 치환기 또는 메틸렌 디옥시에 의해 치환된 페닐이고;Y is a C 4 -C 18 alkylene group, which separates two 4- (R-NH) -1-pyridinidinyl groups by C 4 -C 18 ; R is C 6 -C 18 alkyl group, C 5 -C 7 cycloalkyl group, benzyl or one or two selected from the group consisting of haloken, lower alkyl, lower alkoxy, nitro, cyano and trifluoromethyl Substituents or phenyl substituted by methylene dioxy;

상기 구조식(II)에서;In formula (II) above;

R은 수소, C4-C18의 직쇄 또는 측쇄 알킬기 또는 벤질이며;R is hydrogen, a straight or branched chain alkyl group of C 4 -C 18 or benzyl;

Q는 메틸 또는 염소이고;Q is methyl or chlorine;

V는 0-4의 정수이며;V is an integer from 0-4;

상기 구조식(I) 및 (II)에서;In the above formulas (I) and (II);

A는 음이온; m은 1 또는 3; n은 1 또는 2이고;A is an anion; m is 1 or 3; n is 1 or 2;

X는 1, 2 또는 3이며, 이때(m)(2)=(n)(x)이다.X is 1, 2 or 3, where (m) (2) = (n) (x).

이들 화합물은 항균 및 항진균제로서 유용하며 포진 바이러스에 대해서도 항바이어스 활성이 있다.These compounds are useful as antibacterial and antifungal agents and also have antibias activity against herpes viruses.

구조식(I))의 화합물중 몇몇은 또한 치구 방지제로서 유용하다. 이러한 화합물의 예는 다음과 같다.Some of the compounds of formula (I)) are also useful as jigsaw protectors. Examples of such compounds are as follows.

1,6-비스-[4-(옥틸아미노)-1-피리디늄] 헥산 디브로마이드 및 상응하는 디클로라이드,1,6-bis- [4- (octylamino) -1-pyridinium] hexane dibromide and the corresponding dichloride,

1,6-비스-[4-(노닐아미노)-1-피리디늄] 헥산 디브로마이드 및 상응하는 디클로라이드,1,6-bis- [4- (nonylamino) -1-pyridinium] hexane dibromide and the corresponding dichloride,

1,6-비스-[4-(데실아미노)-1-피리디늄] 헥산 디브로마이드,1,6-bis- [4- (decylamino) -1-pyridinium] hexane dibromide,

1,6-비스-[4-(도데실아미노)-1-피리디늄] 헥산 디브로마이드,1,6-bis- [4- (dodecylamino) -1-pyridinium] hexane dibromide,

1,7-비스-[4-(헵틸아미노)-1-피리디늄] 헵탄 디브로마이드,1,7-bis- [4- (heptylamino) -1-pyridinium] heptane dibromide,

1,7-비스-[4-(옥틸아미노)-1-피리디늄] 헵탄 디브로마이드,1,7-bis- [4- (octylamino) -1-pyridinium] heptane dibromide,

1,7-비스-[4-(노닐아미노)-1-피리디늄] 헵탄 디브로마이드,1,7-bis- [4- (nonylamino) -1-pyridinium] heptane dibromide,

1,7-비스-[4-(데실아미노)-1-피리디늄] 헵탄 디브로마이드,1,7-bis- [4- (decylamino) -1-pyridinium] heptane dibromide,

1,7-비스-[4-(도데실아미노)-1-피리디늄] 헵탄 디브로마이드,1,7-bis- [4- (dodecylamino) -1-pyridinium] heptane dibromide,

1,8-비스-[4-(헵틸아미노)-1-피리디늄] 옥탄 디브로마이드 및 상응하는 디클로라이드,1,8-bis- [4- (heptylamino) -1-pyridinium] octane dibromide and the corresponding dichloride,

1,8-비스-[4-(옥틸아미노)-1-피리디늄] 옥틸 디클로라이드,1,8-bis- [4- (octylamino) -1-pyridinium] octyl dichloride,

1,8-비스-[4-(노닐아미노)-1-피리디늄] 옥탄 디브로마이드,1,8-bis- [4- (nonylamino) -1-pyridinium] octane dibromide,

1,8-비스-[4-(데실아미노)-1-피리디늄] 옥탄 디브로마이드,1,8-bis- [4- (decylamino) -1-pyridinium] octane dibromide,

1,8-비스-[4-(도데실아미노)-1-피리디늄] 옥탄 디브로마이드,1,8-bis- [4- (dodecylamino) -1-pyridinium] octane dibromide,

1,8-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 옥탄 디브로마이드,1,8-bis- [4- (2-ethylhexylamino) -1-pyridinium] octane dibromide,

1,9-비스-[4-(헵틸아미노)-1-피리디늄] 노난 디브로마이드,1,9-bis- [4- (heptylamino) -1-pyridinium] nonane dibromide,

1,9-비스-[4-(노닐아미노)-1-피리디늄] 노나 디브로마이드,1,9-bis- [4- (nonylamino) -1-pyridinium] nona dibromide,

1,9-비스-[4-(데실아미노)-1-피리디늄] 노나 디브로마이드,1,9-bis- [4- (decylamino) -1-pyridinium] nona dibromide,

1,9-비스-[4-(도데실아미노)-1-피리디늄] 노난 디브로마이드,1,9-bis- [4- (dodecylamino) -1-pyridinium] nonane dibromide,

1,10-비스-[4-(헵틸아미노)-1-피리디늄] 데칸 디브로마이드 및 상응하는 디클로라이드,1,10-bis- [4- (heptylamino) -1-pyridinium] decane dibromide and the corresponding dichloride,

1,10-비스-[4-(노닐아미노)-1-피리디늄] 데칸 디브로마이드,1,10-bis- [4- (nonylamino) -1-pyridinium] decane dibromide,

1,10-비스-[4-(데실아미노)-1-피리디늄] 데칸 디브로마이드,1,10-bis- [4- (decylamino) -1-pyridinium] decane dibromide,

1,10-비스-[4-(도데실아미노)-1-피리디늄] 데칸 디브로마이드,1,10-bis- [4- (dodecylamino) -1-pyridinium] decane dibromide,

1,10-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 데칸 디클로라이드,1,10-bis- [4- (2-ethylhexylamino) -1-pyridinium] decane dichloride,

1,12-비스-[4-(헥실아미노)-1-피리디늄] 도데칸 디브로마이드 및 상응하는 디클로라이드,1,12-bis- [4- (hexylamino) -1-pyridinium] dodecane dibromide and the corresponding dichloride,

1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디브로마이드,1,12-bis- [4- (heptylamino) -1-pyridinium] dodecane dibromide,

1,12-비스-[4-(옥틸아미노)-1-피리디늄] 도데칸 디브로마이드1,12-bis- [4- (octylamino) -1-pyridinium] dodecane dibromide

1,12-비스-[4-(노닐아미노)-1-피리디늄] 도데칸 디브로마이드1,12-bis- [4- (nonylamino) -1-pyridinium] dodecane dibromide

1,12-비스-[4-(데실아미노)-1-피리디늄] 도데칸 디브로마이드1,12-bis- [4- (decylamino) -1-pyridinium] dodecane dibromide

1,12-비스-[4-(도데실아미노)-1-피리디늄] 도데칸 디브로마이드1,12-bis- [4- (dodecylamino) -1-pyridinium] dodecane dibromide

1,12-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 도데칸 디브로마이드 및 상응하는 디클로라이드,1,12-bis- [4- (2-ethylhexylamino) -1-pyridinium] dodecane dibromide and the corresponding dichloride,

1,14-비스-[4-(헵틸아미노)-1-피리디늄] 테트라데칸 디브로마이드 및 상응하는 디클로라이드,1,14-bis- [4- (heptylamino) -1-pyridinium] tetradecane dibromide and the corresponding dichloride,

1,14-비스-[4-(옥틸아미노)-1-피리디늄] 테트라데칸 디브로마이드1,14-bis- [4- (octylamino) -1-pyridinium] tetradecane dibromide

그리고 특히 바람직한 화합물로서는,And as particularly preferred compounds,

1,9-비스-[4-(헵틸아미노)-1-피리디늄] 노난 디브로마이드,1,9-bis- [4- (heptylamino) -1-pyridinium] nonane dibromide,

1,10-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 데칸 디브로마이드,1,10-bis- [4- (2-ethylhexylamino) -1-pyridinium] decane dibromide,

1,10-비스-[4-(옥틸아미노)-1-피리디늄] 데칸 디클로라이드 및 상응하는 디브로마이드,1,10-bis- [4- (octylamino) -1-pyridinium] decane dichloride and the corresponding dibromide,

1,9-비스-[4-(옥틸아미노)-1-피리디늄] 노난 디브로마이드,1,9-bis- [4- (octylamino) -1-pyridinium] nonane dibromide,

1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디클로라이드,1,12-bis- [4- (heptylamino) -1-pyridinium] dodecane dichloride,

1,8-비스-[4-(옥틸아미노)-1-피리디늄] 옥탄 디브로마이드,1,8-bis- [4- (octylamino) -1-pyridinium] octane dibromide,

상기 화합물 중 어느 한가지 화합물의 유효량과 제약상 허용되는 담체로 구성된 치구 방지용 구강위생 조성물도 본 발명의 범위에 속한다.An oral hygiene composition for preventing jigsaw consisting of an effective amount of any one of the compounds and a pharmaceutically acceptable carrier is also within the scope of the present invention.

본 발명은 또한 상기 구조식(I) 또는 (II)의 화합물의 유효량과 제약상 허용되는 담체로 구성된 국소 적용에 적합한 항균, 항진균 및 살바이러스용 조성물에 관한 것이다.The present invention also relates to a composition for antimicrobial, antifungal and virucide suitable for topical application consisting of an effective amount of the compound of formula (I) or (II) and a pharmaceutically acceptable carrier.

상기 구조식(Ⅰ)또는 (Ⅱ)의 화합물의 항균, 항진균 및 살바이러스에 유효한 유효량과 제약상 허용디는 계면활성제 및 담체로 구성된 피부세정용 조성물도 역시 본 발명에 속한다.Skin cleaning compositions comprising an effective amount and a pharmaceutically acceptable surfactant and carrier for the antimicrobial, antifungal and killer virus of the compounds of formula (I) or (II) also belong to the present invention.

본 발명은 또한 상기 구조식(Ⅰ)또는 (Ⅱ)의 화합물의 유효량과 적당한 부형제와의 혼합물로 구성되어 무생물 표면에 적용하기에 적합한 항균, 항진균 및 살바이러스용 조성물이 관한 것이다.The present invention also relates to a composition for antimicrobial, antifungal and virucidal, consisting of a mixture of an effective amount of a compound of formula (I) or (II) with a suitable excipient and suitable for application to inanimate surfaces.

구조식(I) 및 (II)의 화합물은 구조식(III)의 4-(R-아미노)피리딘을 구조식(IV)의 이중(di) 치환된 알칸이나 구조식(V)의

Figure kpo00006
,
Figure kpo00007
'-이중 치환된 크실렌과 반응시켜서 제조할 수 있다.Compounds of formulas (I) and (II) may be selected from 4- (R-amino) pyridine of formula (III) or a di-substituted alkane of formula (IV) or a
Figure kpo00006
,
Figure kpo00007
It can be prepared by reacting with '-double substituted xylene.

Figure kpo00008
Figure kpo00008

상기 구조식(IV) 및 (V)에서;In the above formulas (IV) and (V);

Y는 C4-C18의 알킬렌기로서, 두개의 Z기를 C4-C18에 의해 분리시키며;Y is a C 4 -C 18 alkylene group that separates two Z groups by C 4 -C 18 ;

Z-클로로, 브로모, 요오도, 메탄설포닐옥시, 에탄설포닐옥시, 벤젠설포닐옥시, 또는 P-톨루엔설포닐옥시이고;Z-chloro, bromo, iodo, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, or P-toluenesulfonyloxy;

Q는 메틸 또는 염소이며;Q is methyl or chlorine;

V는 0-4의 정수이고;V is an integer from 0-4;

이때, 4-(R-아미노)피리딘(III)을 이중 치환된 알칸(IV)과 반응시킨 경우, 구조식(III)의 R은 C6-C18의 알킬리; C5-C7의 사이클로알킬기, 벤질이거나 또는 할로겐, 저금알킬, 저급 알콕시, 니트로, 시아노 또는 트리플루오로메틸 치환기 1개 또는 2개에 이해 또는 메틸렌디옥시에 의해 치환된 페닐기이며; 4-(R-아미노)피리딘(III)을

Figure kpo00009
,
Figure kpo00010
'-의중 치환된 크실렌(V)과 반응시킬 경우, 구조식(III)의 R은 수조, C1-C18의 직쇄 또는 측홰 알킬기 또는 벤질이다.In this case, when 4- (R-amino) pyridine (III) is reacted with a double substituted alkane (IV), R in structural formula (III) is C 6 -C 18 alkyl; A cycloalkyl group of C 5 -C 7 , benzyl or a phenyl group substituted by methylenedioxy with one or two halogen, lower alkyl, lower alkoxy, nitro, cyano or trifluoromethyl substituents; 4- (R-amino) pyridine (III)
Figure kpo00009
,
Figure kpo00010
When reacted with x-substituted xylene (V), R in formula (III) is a water bath, a straight or branched alkyl group of C 1 -C 18 or benzyl.

구조식(I)에서, 알킬렌기 Y는 직쇄 또는 측쇄의 C4-C18, 바람직하게는 C8-C12를 함유하고 있는 2가의 포화 지방족 탄화수소기로서, 두개의 4-(R-NH)-1-피리디닐기를 C4-C18, 바람직하게는 C8-C12에 의해 분리시킨다.In formula (I), alkylene group Y is a divalent saturated aliphatic hydrocarbon group containing straight or branched C 4 -C 18 , preferably C 8 -C 12 , two 4- (R-NH)- The 1-pyridinyl group is separated by C 4 -C 18 , preferably C 8 -C 12 .

알킬렌기 Y의 예로서는 1, 4-부틸렌, 1, 5-펜틸렌, 1, 6-헥실렌, 1, 7-헵틸렌, 1, 8-옥틸렌, 1, 9-노닐렌, 1, 10-데실렌, 1, 11-운데실렌, 1, 12-도데실렌, 1, 13-트리데실렌, 1, 14-데트라데실렌, 1, 15-펜타데실렌, 1, 16-헥사데실렌, 1, 17-헵타데실렌, 1, 18-옥타데실렌, 1-메틸-1, 4-부틸렌, 3-메틸-1,5-펜틸렌, 2-에틸-1,4-부틸렌, 3-메틸-1,6-헥실렌, 2,4-디메틸-1,5-펜틸렌, 1-메틸-1,7-헵틸렌, 3-에틸-1,6-헥실렌, 3-프로필-1,5-펜틸렌, 4,4-디메틸-1,7-헵틸렌, 2,6-디메틸-1,7-헵틸렌, 2,4,4-트리메틸-1,6-헥실렌, 2,7-디메틸-1,8-옥틸렌, 1-메틸-1,10-데실렌, 5-에틸-1,9-노닐렌, 3,3,6,6-테트라메틸-1,8-옥틸렌, 3,8-디메틸-1,10-데실렌, 3-메틸-1,11-운데실렌, 6-메틸-1,12-도데실렌, 2-메틸-1,13-트리데실렌, 4,9-디메틸-1,12-도데실렌, 4-메틸-1,14-테트라실렌, 2,13-디메틸-1,14-테트라실렌, 1,4-디프로필-1,4-부틸렌, 3-(3-펜틸)-1,5-펜틸렌, 2-(4,8-디메틸노닐))-1,4-부틸렌, 1-헵틸-1,5-펜틸렌 등이 있다.Examples of the alkylene group Y include 1, 4-butylene, 1, 5-pentylene, 1, 6-hexylene, 1, 7-heptylene, 1, 8-octylene, 1, 9-nonylene, 1, 10 -Decylene, 1, 11-undecylene, 1, 12-dodecylene, 1, 13-tridecylene, 1, 14-detradecylene, 1, 15-pentadedecylene, 1, 16-hexadecylene , 1, 17-heptadecylene, 1, 18-octadecylene, 1-methyl-1, 4-butylene, 3-methyl-1,5-pentylene, 2-ethyl-1,4-butylene, 3-methyl-1,6-hexylene, 2,4-dimethyl-1,5-pentylene, 1-methyl-1,7-heptylene, 3-ethyl-1,6-hexylene, 3-propyl- 1,5-pentylene, 4,4-dimethyl-1,7-heptylene, 2,6-dimethyl-1,7-heptylene, 2,4,4-trimethyl-1,6-hexylene, 2, 7-dimethyl-1,8-octylene, 1-methyl-1,10-decylene, 5-ethyl-1,9-nonylene, 3,3,6,6-tetramethyl-1,8-octylene , 3,8-dimethyl-1,10-decylene, 3-methyl-1,11-undecylene, 6-methyl-1,12-dodecylene, 2-methyl-1,13-tridecylene, 4, 9-dimethyl-1,12-dodecylene, 4-methyl-1,14-tetraylene, 2,13-dimethyl-1,14-tetylene, 1,4-dipropyl-1,4-butylene, 3 -(3-pentyl) -1, 5-pentylene, 2- (4,8-dimethylnonyl))-1,4-butylene, 1-heptyl-1,5-pentylene and the like.

Y가 4개의 탄소를 함유할 때는 탄소원자들이 물론 직쇄로 배열되어야 하며, 이와 마찬가지로 Y가 18개의 탄소원자를 함유하고 두개의 4-(R-NH)-1피리디닐기를 C18에 의해 분리시킬 때에도 상기 탄소원자들이 직쇄로 배열되어야 한다 그밖의 경우에는 Y가 직쇄일 수도 있고 측쇄일 수도 있다.When Y contains 4 carbons, the carbon atoms must be linearly arranged as well. Similarly, when Y contains 18 carbon atoms and two 4- (R-NH) -1 pyridinyl groups are separated by C 18 . The carbon atoms should be arranged in a straight chain. In other cases, Y may be linear or branched.

구조식(I)에서 R은 C6-C18, 바람직하게는 C7-C9의 직쇄 또는 측쇄 알킬기이며, 그 예로서는 n-헥실, n-헵틸, n-옥틸, n-노닐, n-데실, n-운데실, n-도데실, n-트리데실, n-테트라데실, n-펜타데실, n-헥사데실, n-헵타데실, n-옥타데실, 1-메틸펜틸, 2,2-디메틸부틸, 2-메틸헥실, 1,4-디메틸펜틸, 2-에틸펜틸, 3-에틸펜틸, 2-메틸헵틸, 1-에틸렉실, 2-에틸렉실, 2-프로필펜틸, 2-메틸-3-에틸펜틸 1,3,5-트리메틸헥실, 1,5-디메틸-4-에틸헥실, 2-프로필헵틸, 5-메틸-2-부틸헥실, 2-프로필노닐, 2-부틸옥틸, 1,1-디메틸운데실, 2-펜틸노닐, 1,2-디메틸테트라데실, 1,1-디메틸펜타데실 등이 있다.R in formula (I) is a straight or branched chain alkyl group of C 6 -C 18 , preferably C 7 -C 9 , for example n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, 1-methylpentyl, 2,2-dimethyl Butyl, 2-methylhexyl, 1,4-dimethylpentyl, 2-ethylpentyl, 3-ethylpentyl, 2-methylheptyl, 1-ethyllexyl, 2-ethyllexyl, 2-propylpentyl, 2-methyl-3- Ethylpentyl 1,3,5-trimethylhexyl, 1,5-dimethyl-4-ethylhexyl, 2-propylheptyl, 5-methyl-2-butylhexyl, 2-propylnonyl, 2-butyloctyl, 1,1- Dimethyl undecyl, 2-pentylnonyl, 1,2-dimethyltetradecyl, 1,1-dimethylpentadecyl, and the like.

구조식(I)에서 R이 C5-C7의 사이클로 알킬기일 때에는 사클로 펜틸, 사이클로헥실, 사이클로헵틸 등이 포함된다.In the formula (I), when R is a C 5 -C 7 cycloalkyl group, saclopentyl, cyclohexyl, cycloheptyl and the like are included.

구조식(I)에서 R이 할로겐, 저급 알킬, 저급 알콕시, 니트로, 시아노 및 트리플루오로메틸로 구성된 군에서 선택된 1-2개의 치환기에 의해 또는 메틸렌디옥시에 의해 치환된 페닐인 경우에는 P-클로로페닐, O-클로로페닐, m-클로로페닐, P-브로모페닐, m-플루오로페닐, P-요오도페닐, 2,4-디클로로페닐, 2,4-디플루오로페닐, 2,5-디브로모페닐, 3,5-디클로로페닐, 3-클로로-4-플로오로페닐, 3,4-메틸렌디옥시페닐, P-에닐페닐, P-메톡시페닐, m-니트로페닐, O-시아노페닐, m-(트리플루오로메틸)페닐, 2-메톡시-5-메틸페닐 등이 포함된다.P in the formula (I) when R is phenyl substituted by 1-2 substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, nitro, cyano and trifluoromethyl or by methylenedioxy Chlorophenyl, O-chlorophenyl, m-chlorophenyl, P-bromophenyl, m-fluorophenyl, P-iodophenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 2,5 -Dibromophenyl, 3,5-dichlorophenyl, 3-chloro-4-fluorophenyl, 3,4-methylenedioxyphenyl, P-enylphenyl, P-methoxyphenyl, m-nitrophenyl, O- Cyanophenyl, m- (trifluoromethyl) phenyl, 2-methoxy-5-methylphenyl and the like.

구조식(II)에서 R은 C1-C13, 바람직하게는 C6-C12의 직쇄 또는 측홰 알킬기이며, 상기 언급한 C6-C18의 알킬기 이외에도 메틸, 에틸, n-프로필, n-부틸, n-펜틸, 이소프로필, 1-메틸프로필, 이소부틸, 3차 부틸, 이소펜틸, 네오펜틸, 1-메틸펜틸 등과 같은 기가 포함된다.R in formula (II) is a straight or branched alkyl group of C 1 -C 13 , preferably C 6 -C 12 , and in addition to the alkyl groups of C 6 -C 18 mentioned above, methyl, ethyl, n-propyl, n-butyl , groups such as n-pentyl, isopropyl, 1-methylpropyl, isobutyl, tertiary butyl, isopentyl, neopentyl, 1-methylpentyl and the like.

구조식(I) 및 (II)에서 R은 또한 벤질기일 수 있다. 소망에 따라, 벤질기의 페닐부분은 예컨데 할로겐, 하이드록시, 저급 알킬, 저급 알콕시, 니트로, 시아노, 트리플루오로메틸 등과 같은 1-2개의 치환환기로 치환될 수 있다.R in formulas (I) and (II) may also be a benzyl group. If desired, the phenyl moiety of the benzyl group may be substituted with 1-2 substituents such as halogen, hydroxy, lower alkyl, lower alkoxy, nitro, cyano, trifluoromethyl and the like.

R은 구조식(I)과 (II)에서 동일하다.R is the same in formulas (I) and (II).

상기 구조식에서 A가 음이온인 경우에는, 예컨데 브로마이드, 클로라이드, 플루오라이드, 아이오다이드, 설페이드, 포스페이트, 나이트레이트, 설파메이트, 메탄설포네이트, 에탄설포네이트, 벤젠설포네이트, P-톨루엔설포네이트, 나프탈렌설포네이트, 나프탈렌설포네이트, 사이클로헥실설파메이트, 아세테이트, 트리플루오로아세테이트, 말레이트, 푸마레이트, 석시네이트, 타트레이트, 옥살레이트, 시트레이트, 락테이트, 글루코네이트, 아스콜베이트, 락데이트, 프탈레이트, 살리실레이트, 벤조에이트, 피크레이트, 메탄포스페이트, 알제나이트, 알제네이트, 티오설페이트, 피클로레이트, 타트로네이트, 살코시네이트, N-라우로일살코시네이트, 모노플루오로포스페이트, 헥사플루오로알루미네이트, 헥사플루오로실리케니트, 헥사플루오로스타네이트, 플루오로지르코네이트, 테트라플루오로보레이트, 헥사클로로플라티네이트, 테트라클로로알루미네이트, 헥사클로로스타네이트 등과 같은 유기산 및 무기산의 음이온을 모두 포함한다. 이때 브로마이드과 클로라이드가 바람직하다.When A is an anion in the above formula, for example bromide, chloride, fluoride, iodide, sulfide, phosphate, nitrate, sulfamate, methanesulfonate, ethanesulfonate, benzenesulfonate, P-toluenesulfonate , Naphthalenesulfonate, naphthalenesulfonate, cyclohexylsulfate, acetate, trifluoroacetate, malate, fumarate, succinate, tartrate, oxalate, citrate, lactate, gluconate, ascorbate, lactate Dates, Phthalates, Salicylates, Benzoates, Piclates, Methanephosphates, Algenites, Alzenates, Thiosulfates, Picchlorates, Tatronates, Salcosinates, N-lauroyl salcosinates, Monofluorophosphates Hexafluoroaluminate, hexafluorosiliconite, hexafluorostannate, It includes both anions of organic and inorganic acids such as fluorozirconate, tetrafluoroborate, hexachloroplatinate, tetrachloroaluminate, hexachlorostannate and the like. In this case, bromide and chloride are preferable.

여기서 ＂할로겐＂이란 말은 블루오로, 염소, 브롬 및 요오드를 뜻한다.The term "halogen" here means blue auro, chlorine, bromine and iodine.

저급 아릴 및 저급 알콕시란 말에서 ＂저급＂은 메틸, 에틸, 프로필, 이소프로필, 부틸, 이소부틸 및 3차 부틸과 같은 C1-C4의 알킬부분을 뜻한다.In the term lower aryl and lower alkoxy, “lower” refers to an alkyl moiety of C 1 -C 4 , such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tertiary butyl.

상기 구조식(I) 또는 (II)의 화합물은 2몰의 4-(R-아미노)피리딘[구조식(III)과 1몰의 적당히 이중 치환된 알칸이나 크실렌[구조식(IV) 또는 (V)]을 예컨데 저급 알칸올, 아세토니트릴, N,N-디메틸포름아미드, N,N-디메틸아세트아믿, 벤젠, 톨루엔, 크실렌과 같은 불활성 용매내, 약 80°-150℃의 온도에서 1-24시간 동안 반응시켜 제조하는 것이 편리하다. 일반적으로 반응체는 아세토니트릴 또는 N,N-디메틸포름아미드나 이들의 혼합 용매, 또는 저급 알칸올 중에서 60℃-100℃의 온도로 2-20시산동안 가열 시킨다.The compound of formula (I) or (II) may contain 2 moles of 4- (R-amino) pyridine [formula (III) and 1 mole of moderately double substituted alkane or xylene [formula (IV) or (V)] Reaction in an inert solvent such as, for example, lower alkanol, acetonitrile, N, N-dimethylformamide, N, N-dimethylacetaceur, benzene, toluene, xylene, at a temperature of about 80 ° -150 ° C. for 1-24 hours. It is convenient to make it. In general, the reactants are heated in acetonitrile or N, N-dimethylformamide, a mixed solvent thereof, or lower alkanol at a temperature of 60 ° C.-100 ° C. for 2-20 acids.

반응은 또한 용매없이 화학양론적 양의 반응체를 120-150℃로 2-5시간 동안 가열함으로서 수행될 수 있다.The reaction can also be carried out by heating the stoichiometric amount of the reactant to 120-150 ° C. for 2-5 hours without solvent.

반응의 결과 생성된 비스-[4-(R-아미노)-1-피리디늄] 화합물 [구조식(I) 및(II)]은 예컨데 생성물이 반응매질에 불용성인 경우에는 여과시켜서, 또는 에테르, 벤젠 또는 헥산과 같은 비극성 용매와의 반응혼합물은 희석시켜 생성물을 침전시킴으로써, 또는 반응 매질을 증발시켜 생성물을 잔사로 남게하는 등의 통상의 방법으로 단리시킨다. 단리된 조잡한 생성물은 예컨데 활성탄 또는 규조토와 같은 흡착제의 존재하에서 적당한 용매로 결정화 시켜 정제할 수 있다.Bis- [4- (R-amino) -1-pyridinium] compounds produced as a result of the reaction [Formulas (I) and (II)] are, for example, filtered if the product is insoluble in the reaction medium, or ether, benzene Or the reaction mixture with a nonpolar solvent, such as hexane, is isolated by conventional methods such as dilution to precipitate the product, or by evaporating the reaction medium to leave the product as a residue. The isolated crude product can be purified by crystallization with a suitable solvent, for example in the presence of an adsorbent such as activated carbon or diatomaceous earth.

상기의 방법에 따라 제조된 비스-4-(R-아미노)-1-피리디늄] 화합물은 이중치환된 알칸이나 크실렌 반응체의 분리된 기[구조식(IV) 및 (V)에서의 Z]에 상응하는 음이온 [구조식(I)및 (II))에서의 A]을 함유하게 된다.The bis-4- (R-amino) -1-pyridinium] compound prepared according to the above method is applied to the separated groups [Z in Structural Formulas (IV) and (V)] of a bisubstituted alkane or xylene reactant. It will contain the corresponding anions [A in structural formulas (I) and (II)].

그러나, 이들 화합물의 음이온 부분은 소망에 따라 예컨대 메탄올, 에탄올 또는 물과 같은 적당한 용매내의 피리디늄 화합물 용액을 소망의 음이온을 함유한 합성이온 교환수지대로 통과시키는 통상의 이온교환법에 따라 변경시킬 수 있다. 용매를 증발시키고, 그 결과 생성된 소망의 음이온을 함유한 피리디늄 화합물은 적당한 용매로 부터 재결정시켜 정제한다.However, the anion moiety of these compounds may be modified according to conventional ion exchange methods, where desired, for example, passing a solution of pyridinium compound in a suitable solvent such as methanol, ethanol or water to a synthetic ion exchange resin containing the desired anion. . The solvent is evaporated and the resulting pyridinium compound containing the desired anion is purified by recrystallization from a suitable solvent.

또한 피리디늄 화합물은 피리디늄 화합물의 음이온과 결합하여 불용성 침전을 생성하는 대응하는 양이온과 관련된 소망의 음이온을 함유하는 기용성 염과 반응시키 룻 있다. 이때 상기 불용성 침전을 분리시키면 소망의 음이온을 함유하는 피리디늄 화합물 용액이 남는다. 예를 들면, 비스-(4-(R-아미노)-1-피리디늄] 알칸 디할라이드를 유기산 또는 무기산의 은염과 반응시킨다. 침전된 할라이드를 제거하면 소망의 유기산 또는 무기산 음이온을 함유한 피리디늄 화합물 용액이 남는다.The pyridinium compound is also reacted with a soluble salt containing the desired anion associated with the corresponding cation which binds with the anion of the pyridinium compound to produce an insoluble precipitate. At this time, separation of the insoluble precipitate leaves a pyridinium compound solution containing the desired anion. For example, a bis- (4- (R-amino) -1-pyridinium] alkane dihalide is reacted with a silver salt of an organic or inorganic acid, which removes the precipitated halides and pyridinium containing the desired organic or inorganic acid anion. The solution of the compound remains.

상기와 같은 복분해 반응은 또한 불용성 피리디늄 화합물을 제조하는데 사용될 수 있다. 가용성 비스-(4-(R-아미노)-1-피리디늄] 화합물은, 피리디늄 양이온과 결합하여 소망의 생성물인 불용성 침전을 형성할 수 있는 소망의 음이온을 함유한 가용성 염과 반응시킨다. 이들 불용성 피리디늄 염은 단리 및 정제의 목적으로 유용하며, 이들을 에멀젼, 크림, 페이스트(paste), 로숀, 젤리, 또는 분말로 적당히 조합하면, 이들은 또한 서서히 지속적으로 유리되는 살균성 피리디늄 화합물을 제공해주는 축적질(depot)의 제조제로 사용될 수도 있다.Such metathesis reactions can also be used to prepare insoluble pyridinium compounds. Soluble bis- (4- (R-amino) -1-pyridinium] compound is reacted with a soluble salt containing the desired anion, which can bind to the pyridinium cation to form an insoluble precipitate, the desired product. Insoluble pyridinium salts are useful for isolation and purification purposes, and when properly combined with emulsions, creams, pastes, lotions, jellies, or powders, they also accumulate to provide a bactericidal pyridinium compound that is slowly and continuously liberated. It can also be used as a preparation for the depot.

더욱이 어떤 음이온으로 이루어진 불용성 염은 치구 방지제의 치아 착색력을 감소시키는데 유효하다.Moreover, insoluble salts consisting of certain anions are effective in reducing tooth pigmentation of jigsaws.

이와 같이, 주어진 화합물의 음이온 부분은 그 종류에 따라 용해도, 안정도, 분자량, 생체내 독성과 같은 특성을 가지고 있으며, 화합물의 형태가 바라는 목적에 부적당할 경우에는 이 음이온 부분을 더욱 적합한 다른 형태로 쉽게 전환시킬 수 있다. 피부 또는 기타 조직이나 구강내에 적용하기 위하여서는, 플루오로, 염소, 브롬, 요오드, 메탄설포네이트와 같은 제작상 허용되는 음이온이 사용된다.As such, the anion moiety of a given compound has properties such as solubility, stability, molecular weight, and in vivo toxicity, depending on the type of compound, and if the form of the compound is inadequate for the desired purpose, the anion moiety is more readily available in another form. You can switch. For application in the skin or other tissues or oral cavity, manufacturing acceptable anions such as fluoro, chlorine, bromine, iodine, methanesulfonate are used.

출발물질로 사용되는 4-(R-아미노) 피리딘류 [구조식(III)]는 일반적으로 공지되어 있으며, 특별히 신규한 것이라 할지라도 공지 화합물을 제조하는 방법에 따라 제조할 수 있다.4- (R-amino) pyridines [formula (III)], which are used as starting materials, are generally known and can be prepared according to the method for preparing known compounds, even if they are particularly novel.

4-(R-아미노) 피리딘류는 4-클로로 또는 4-브로모피리딘 또는 N-(4-피리딘)-피리디늄 클로라이드 하이드로클로라이드를 적당히 치환된 아민과 반응시켜 제조할 수 있다. 반응은 일반적으로 반응체를 용매없이 150-225℃에서 1.5-3시간 동안 가열하여 수행한다. 생성물은 예컨대 알칼리 수성매질로부터 에테르, 메틸렌클로라이드 또는 클로로포름과 같은 유기용매내로 추출시키고, 유기용매를 증발시키고, 잔사를 적당한 용매로 결정화시키는 등의 통상의 방법으로 단리된다.4- (R-amino) pyridines can be prepared by reacting 4-chloro or 4-bromopyridine or N- (4-pyridine) -pyridinium chloride hydrochloride with an appropriately substituted amine. The reaction is generally carried out by heating the reactants at 150-225 ° C. for 1.5-3 hours without solvent. The product is isolated, for example, from an alkaline aqueous medium into an organic solvent such as ether, methylene chloride or chloroform, the organic solvent is evaporated, and the residue is crystallized with a suitable solvent.

또한, 4-(R-아미노)피리딘은 적당한 탄소함량을 함유한 카보닐화합물과 4-아미노피리딘을 함유한 혼합물을 접촉환원시켜서 제조할 수도 있다. 이때의 반응은 일반적으로 예컨대 에탄올과 같은 적당한 용매중에서 50-70℃의 온도, 20-60pai의 수소압하에서 팔라듐 수소첨가 촉매의 존재하에서 수행된다. 수소첨가 시간은 대개 4-10시간이면 충분하다. 200% 이상의 과량의 카보닐 화합물을 사용하면 반응시간 5시간 이내에 높은 수율의 순수한 생성물을 얻는데 유리하다. 촉매를 제거하고 용매를 증발시켜 생성물을 단리시킨 후, 잔사를 증류시키거나 적당한 용매로 결정화 시킨다.In addition, 4- (R-amino) pyridine may be prepared by catalytic reduction of a mixture containing a carbonyl compound and 4-aminopyridine containing a suitable carbon content. The reaction at this time is generally carried out in the presence of a palladium hydrogenation catalyst at a temperature of 50-70 ° C., hydrogen pressure of 20-60 Pa in a suitable solvent such as ethanol. The hydrogenation time is usually 4-10 hours is sufficient. The use of excess carbonyl compound in excess of 200% is advantageous for obtaining a high yield of pure product within 5 hours of reaction time. After the catalyst is removed and the solvent is evaporated to isolate the product, the residue is either distilled off or crystallized with a suitable solvent.

적당한 탄소함량을 가지고 있는 알데히드를 고온에서 포름산 존재하에 4-아미노피리딘과 반응시켜고 4(R-아미노)피리딘을 얻을 수 있다.Aldehydes having the appropriate carbon content can be reacted with 4-aminopyridine in the presence of formic acid at high temperature to afford 4 (R-amino) pyridine.

4(R-아미노)피리딘은 또한 4-아미노피리딘을 적당한 탄소함량을 가진 아실할라이드로 아실화시키고, 이때 생성된 아미드를 환원시켜 얻을 수도 있다. 아실화는, 예컨대 4-아미노피리딘을 메틸렌디클로라이드 또는 클로로포름과 같은 불활성 용매내에서 트리에틸아민과 같은 산 수용체의 존재하에 아실할라이드와 반응시키는 등의 공지된 방법에 따라 수행된다. 이와 같이 생성된 아미드를 테트라하이드로푸란, 에테르, 또는 디옥산과 같은 적당한 용매중에서 리튬하이드라이드와 같은 착금속 하이드라이드로 환원시키고, 이어 아민 생서물을 공지된 방법으로 단리시킨다.4 (R-amino) pyridine can also be obtained by acylating 4-aminopyridine with an acyl halide having the appropriate carbon content, at which time the resulting amide is reduced. Acylation is carried out according to known methods, for example by reacting 4-aminopyridine with an acyl halide in the presence of an acid acceptor such as triethylamine in an inert solvent such as methylenedichloride or chloroform. The amides thus produced are reduced with a complex metal hydride such as lithium hydride in a suitable solvent such as tetrahydrofuran, ether, or dioxane, and the amine preparation is isolated by known methods.

출발물질로 사용되는 구조식(IV)의

Figure kpo00011
,
Figure kpo00012
'-이중치환 알칸류는 대개 공지의 화합물이며, 특별히 신규한 것이라 할지라도 공지의 화합물을 제조하는 방법으로 제조할 수 있다.Of structural formula (IV) used as starting material
Figure kpo00011
,
Figure kpo00012
The '-disubstituted alkanes are usually known compounds, and even if they are particularly novel, they can be produced by a method for producing known compounds.

출발물질로 사용되는 구조식(III)의

Figure kpo00013
,
Figure kpo00014
'-이중치환 크실렌류도 일반적으로 공지된 화합물이며, 특별히 신규한 것이라 할지라도 공지의 화합물을 제조하는 방법으로 제조할 수 있다.Of structural formula (III) used as starting material
Figure kpo00013
,
Figure kpo00014
'-Double substituted xylenes are also generally known compounds, and even though they are particularly novel, they can be prepared by a method for producing known compounds.

적당한 클로로 또는 메틸로 치환된 프탈산, 이소프탈산, 또는 테레프탈산 또는 이들의 에스테르를 테트라하이드로푸란, 에테르 또는 디옥 산과 같은 적당한 용매중에서 리튬 알미늄 하이드라이드와 같은 금속 하이드라이드와 반응시키면 상응하는 크실렌-

Figure kpo00015
,
Figure kpo00016
'-디올로 환원된다. 생성된 크실렌-
Figure kpo00017
,
Figure kpo00018
'-디올을 예컨대 브롬화수소, 포르포러스 트리브로마이드, 포르포러스 옥시클로라이드 티오닐 클로라이드 또는 요오드화 칼륨 및 오르토 인산과 공지의 방법으로 반응시키면,
Figure kpo00019
,
Figure kpo00020
'-디할로크실렌으로 전환된다. 크실렌-
Figure kpo00021
,
Figure kpo00022
'-디올을 또한 예컨대 피리딘과 같은 산수용체 존재하에 메탄-, 에탄-, 벤젠-또는 P-톨루엔설폰닐클로라이드와 공지의 방법으로 반응시켜 설포네이트에스테르로 전환시킬 수도 있다.Phthalic acid, isophthalic acid, or terephthalic acid or esters thereof substituted with a suitable chloro or methyl can be reacted with a metal hydride such as lithium aluminum hydride in a suitable solvent such as tetrahydrofuran, ether or dioxane.
Figure kpo00015
,
Figure kpo00016
Reduced to '-diol. Generated Xylene-
Figure kpo00017
,
Figure kpo00018
When the '-diol is reacted with a known method with, for example, hydrogen bromide, phosphorus tribromide, phosphorus oxychloride thionyl chloride or potassium iodide and ortho phosphoric acid,
Figure kpo00019
,
Figure kpo00020
Converted to dihaloxylene. xylene-
Figure kpo00021
,
Figure kpo00022
'-Diol can also be converted to sulfonate esters by reaction with methane-, ethane-, benzene- or P-toluenesulfonylchloride in the presence of an acid acceptor such as pyridine, for example.

다음에 자세히 설명하겠지만, 구조식(I) 및 (II)의 화합물은 그 양성 및 그람음성균, 몇몇 진균류 및 포진바이러스를 포함한 미생물들에 대해 시험관내 항균활성을 나타낸다. 따라서 이 화합물들은 인간 피부나 기타 조직의 세균제거 및 무생물 표면을 위생화하고 소독하는데 국부적으로 적용할 수 있는 살균제 또는 방부제로서 사용될 수 있다. 이들 화합물은 부상자를 치료하기 위한 국소 방부용액, 또는 외과적 손세정, 환자의 수술전 피부용제제, 비누 및 삼푸와 같은 함균 세정제, 또는 가정용과 공업용 세척제 및 소독약, 그리고 페인트, 니스 및 왁스와 같은 보호 표면제로 사용될 수 있다. 이들 화합물을 통상의 희석제 또는 담체, 허용 가능한 양이온성, 음이온성, 또는 비이온성 계면활성제, 완충제, 향료 및 착색제와 혼합하여 상기 용도에 사용하며, 이들을 문지르기(scrubbing), 분무, 면봉(綿捧), 액침(液浸)과 같은 통상의 방법으로 소독될 표면에 적용시킨다.As will be described in detail below, the compounds of formulas (I) and (II) exhibit in vitro antimicrobial activity against microorganisms, including their positive and Gram-negative bacteria, some fungi and herpes viruses. Therefore, these compounds can be used as fungicides or preservatives that can be applied locally to sanitize and disinfect human skin or other tissues, and to sanitize and disinfect non-living surfaces. These compounds can be used in topical antiseptic solutions, or surgical hand washes to treat injured people, preoperative skin preparations for patients, antibacterial cleaners such as soaps and shampoos, or household and industrial cleaners and disinfectants, and protective surfaces such as paints, varnishes and waxes. Can be used zero. These compounds are mixed with conventional diluents or carriers, acceptable cationic, anionic or nonionic surfactants, buffers, flavorings, and coloring agents for use in these applications and are used for scrubbing, spraying, and swabing. ) Is applied to the surface to be sterilized by conventional methods such as immersion.

피부 세정제로 쓰기 위하여서는, 비스-[4-(R-아미노)-1-피리디늄] 화합물을 액체상태로 제조할수 있으며, 또는 소망에 따라 액체 제제에 어떤 첨가제를 가해 농후하게 하여 겔이나 페이스ㅡ(paste)로 할 수도 있고, 또는 공지의 방법에 따라 바(bar)의 형태로 할 수도 있다. 예를 들어, 이 화합물은 제약상 허용되는 계면활성제, 바람직하게는 공지의 화합물인 폴리옥세에틸렌-폴리옥시프로필렌 공중합체와 같은 비이온성 계면 활성제 및 스테아릴 디메틸 아민 옥사이드 등과 같은 아민옥사이드류 또는이들의 혼합물과 함게 제제화될 수 있다. 이들 제제는 또한, 물, 저급 알칸올 등과 같은 제약상 허용되는 희석제 및 pH를 5.0-7.5로 유지하기 위한 산, 염기, 또는 완충제, 그리고 경우에 따라서는 향료 및 착색제를 함유할 수 있다. 비스-[4-(R-아미노)-1-피리디늄] 화합물의 제제내의 농도는 일반적으로 약 0.5-2.0중량% 바람직하게는 1.0중량%이다.To use as a skin cleanser, bis- [4- (R-amino) -1-pyridinium] compounds can be prepared in the liquid state or, if desired, added to the liquid formulations with a certain additive to thicken it to give a gel or face. It may be made into (paste) or may be in the form of a bar according to a known method. For example, these compounds are pharmaceutically acceptable surfactants, preferably nonionic surfactants such as polyoxeethylene-polyoxypropylene copolymers, known compounds and amine oxides such as stearyl dimethyl amine oxide, or the like. It may be formulated with a mixture. These formulations may also contain pharmaceutically acceptable diluents, such as water, lower alkanols, and the like, and acids, bases, or buffers to maintain the pH at 5.0-7.5, and optionally flavoring and coloring agents. The concentration in the formulation of the bis- [4- (R-amino) -1-pyridinium] compound is generally about 0.5-2.0% by weight, preferably 1.0% by weight.

팅크제를 만들경우에는, 비스-[4-(R-아미노)-1-피리디늄] 화합물을 1, 아세톤과 같은 저급 알칸올, 그리고 에탄올과 같은 저급 알톤올과 함께 제제화시킬 수 있다. 필요한 경우에는 팅크제를 착색제로 착색시킬 수도 있다. 활성성분의 농도는 일반적으로 약 0.05-1.0%(w/v)로서, 0.1%(w/v)인 것이 바람직하다.When making tinctures, bis- [4- (R-amino) -1-pyridinium] compounds can be formulated with 1, lower alkanols such as acetone, and lower altonols such as ethanol. If necessary, the tincture may be colored with a colorant. The concentration of the active ingredient is generally about 0.05-1.0% (w / v), preferably 0.1% (w / v).

또한 이들 화합물은 예컨대 이들을 알킬 폴리에테르, 알콜, 세틸 알콜, 스테아릴 알콜과 같은 통상의 로숀, 연고 또는 크림 기제에 혼합시켜 로숀제, 연고제, 또는 이들을 전분, 활석( 활 石)과 같은 통상의 분말 기체에 혼입시켜 분말로 하거나, 또는 이들을 글리세롤 및 트라가칸드와 같은 통상의 젤리 기제에 혼입시켜 젤리제로하는 등 적당한 제약상 부형제내로 제제화하여 박테리아, 진균 및 포진바이러스 감염 치료에 사용할 수 있다. 이들은 또한 에어로졸 분무 또는 포말로 사용하기 위해 제제화될 수도 있다.These compounds may also be mixed with conventional lotions, ointments or cream bases such as, for example, alkyl polyethers, alcohols, cetyl alcohols, stearyl alcohols, and the like, such as lotions, ointments, or conventional powders such as starch, talc. It can be formulated into suitable pharmaceutical excipients such as incorporation into a gas to make powders or incorporation into conventional jelly bases such as glycerol and tragacand into jelly to be used for the treatment of bacterial, fungal and herpes virus infections. They may also be formulated for use as aerosol sprays or foams.

무생물 표면의 위행화나 소독용으로 쓸 경우에는, 이들 화합물을 트리소디움 포르페이트, 붕사 등과 같은 공지의 세정제 및 비누 혼합제와 함께 제제화시킬 수 있다. 이던 제제내에 존재하는 비스-[4-(R-아미노)-1-피리디늄] 화합물의 농도는 약 10중량%까지이다.When used for hypocrisy or disinfection of inanimate surfaces, these compounds can be formulated with known detergents and soap mixtures such as trisodium phosphate, borax and the like. The concentration of bis- [4- (R-amino) -1-pyridinium] compound present in the formulation is up to about 10% by weight.

다음에 상세히 설명될 바와 같이, 구조식(I)의 화합물중 어떤 것은 치구의 형성을 방지하는데 유효하다. 이런 목적에 사용할 경우에는, 이들 화합물을 함수제(mouthwash)나 치마제(齒磨劑)의 제형으로 치아에 편리하게 적용할 수 있다. 이들 화합물은 치마제나 함수제에 사용되는 통상의 성분(예컨대 물, 알콘, 클리세린, 완충액, 농후제, 향료 및 착색제)과 혼합할 수 있다. 이들 제제는 또한 임의로 치아 착색의 가능성을 감소시키는데 유효한 공지의 성분, 특히 예컨대 아연 페놀설페이트, 8-하이드록시퀴놀린, 디소디움 에탄, 1-하이드록시-1,1-디포스페이트 등과 같은 공지의 화합물인 항결석제(antl-calculua agents) 및 예컨대 니트로트리초산, 2-하이드록시에틸니트릴로디초산 또는 그의 수용성 염과 같은 공지의 화합물 인 아미노 카복실레이트 화합물과 같은 것을 함유할 수 있다. 이런 제제내의 비스-[4-(R-아미노)-1-피리디늄]알칸의 농도는 일반적으로 약 0.005-0.05중량%로서, 약 0.01중량%인 것이 바람직하다.As will be explained in detail below, any of the compounds of formula (I) is effective for preventing the formation of jig. When used for this purpose, these compounds can be conveniently applied to the teeth in the formulation of mouthwash or dentifrice. These compounds can be mixed with conventional ingredients used in dentifrices or water solubles, such as water, alcons, glycerin, buffers, thickeners, flavoring and coloring agents. These preparations are also known ingredients that are optionally effective for reducing the likelihood of tooth pigmentation, in particular known compounds such as zinc phenolsulfate, 8-hydroxyquinoline, disodium ethane, 1-hydroxy-1,1-diphosphate, and the like. Anti-calculus agents and the like, such as amino carboxylate compounds which are known compounds such as nitrotriacetic acid, 2-hydroxyethylnitrilodiacetic acid or water soluble salts thereof. The concentration of bis- [4- (R-amino) -1-pyridinium] alkanes in such formulations is generally about 0.005-0.05% by weight, preferably about 0.01% by weight.

상기의 제제내의 함유된 부형제, 희석제, 담체 및 첨가제는 활성성분과 양립할 수 있는 것으로서, 비스-[4-(R-아미노)-1-피리디늄]화합물의 항균, 항진균 및 바이러스 살균 효과가 담체, 희석제, 부형제 또는 기타 첨가제의 속성에 의해 경감되지 않는 것이어야 한다.The excipients, diluents, carriers and additives contained in the above formulations are compatible with the active ingredient, and the antimicrobial, antifungal and viral bactericidal effects of the bis- [4- (R-amino) -1-pyridinium] compound are carriers. Should not be mitigated by the nature of the diluents, excipients or other additives.

본 발명의 화합물의 분자구조는 적외선 스펙트럼 및 핵자기공명(NMR) 스펙트럼에 의해 결정되었으며, 이론치와 원소분석에 의한 계산치의 일치에 의해 확정되었다.The molecular structure of the compound of the present invention was determined by infrared spectra and nuclear magnetic resonance (NMR) spectra, and was confirmed by agreement of theoretical and calculated values by elemental analysis.

다음 실시예는 본 발명을 상세히 설명해 주는 것으로서, 본 발명이 이에 제한되는 것은 아니다.The following examples illustrate the invention in detail, but the invention is not limited thereto.

[실시예 1]Example 1

A. 4-브로모피리딘 하이드로클로라이드 130g(0.67몰)과 n-헵틸아민 하이드로클로라이드 152g(1.0몰)을 함유한 혼합물을 유(油)욕에서 가열했다. 욕의 온도가 180-185℃도 되었을 때 반응혼합물이 용융하기 시작했으며, 이때 교반을 시작했다. 190-195℃에서 용융이 완결된 후, 이 액체 혼합물을 교반하고 210-220℃에서 2.5시간동안 가열했다. 반응혼합물을 실온까지 냉각하고, 이때 생성된 고형질을 물에 녹이고, 35% 수산화나트륨 수용액을 가하여 알칼리성으로 하고, 생성물을 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황산나트륨 상에서 건조시키고, 감압하에서 증발건조시켰다. 결과 생긴 점성이 있는 기름을 소량의 n-헥산으로 희석하고 냉각하여 고체를 얻고, 이것을 여과하여 모아서 공기 건조시킴으로써, 융점이 49-51℃인 4-(헵틸아미노) 피리딘 86.6g을 얻었다.A. A mixture containing 130 g (0.67 mole) of 4-bromopyridine hydrochloride and 152 g (1.0 mole) of n-heptylamine hydrochloride was heated in an oil bath. When the temperature of the bath was 180-185 ° C., the reaction mixture began to melt, at which point stirring was started. After melting was complete at 190-195 ° C., the liquid mixture was stirred and heated at 210-220 ° C. for 2.5 hours. The reaction mixture was cooled to room temperature, and the resulting solid was dissolved in water, and made alkaline by adding 35% aqueous sodium hydroxide solution, and the product was extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The resulting viscous oil was diluted with a small amount of n-hexane and cooled to obtain a solid, which was collected by filtration and air dried to give 86.6 g of 4- (heptylamino) pyridine having a melting point of 49-51 ° C.

B. 앞서와는 달리, 4-(헵틸아미노)피리딘을 다음의 방법으로 제조했다. 즉, N-(4-피리딜)피리디늄 클로라이드 하이드 클로라이드 229g(1.0몰)과 n-헵틸아민 하이드로클로라이드 228g(1.5몰)의 혼합물을 215℃의 유욕에서 2시간 동안 교반하면서 사열했다. 반응 혼합물을 80℃로 냉각하고 얼음물로 희석한 후, 35% 수산화나트륨 수용액을 가하여 알칼리성으로 하고, 에테르 및 클로로포름으로 연속적으로 추출했다. 유기 추출물을 모아 감압하에서 증발 건조시켰다. 이때 잔류한 점성이 있는 기름을 에테르에 용해 시키고, 에테르성 수용액을 물로 세척했다. 수성 세척액을 클로로포름으로 역추출(back-exteact)하고, 클로로포름 추출물은 에테르성 용액과 혼합했다. 혼합된 유기용액을 무수 황산 나트륨 상에서 건조시키고, 감압하에서 증발건조시켰다. 잔류 기름을 78℃로 냉각시켜 부분적으로 고형화시켰다. 이와 같이 얻을 반고체를 소량의 에테르로 희석한 후 여과했다. 그 결과 얻어진 고체를 아세토니릴과 클로로포름의 혼합물에 용해시키고, 이 용액을 활성탄으로 처리하여 여과한 후, 여액을 감압하에서 증발 건조시켰다. 생성된 반고체를 소량의 에테르로 희석하고, 냉각시켰다. 결과 생성된 고체를 여과하여 모으고, 소량의 차가운 에테르로 세척하고 건조하여ㅡ 융점이 50-52℃인 4-(헵틸아미노)피리딘 84.6g을 얻었다.B. Unlike the above, 4- (heptylamino) pyridine was prepared by the following method. That is, a mixture of 229 g (1.0 mole) of N- (4-pyridyl) pyridinium chloride hydrochloride and 228 g (1.5 mole) of n-heptylamine hydrochloride was burnt while stirring in an oil bath at 215 ° C for 2 hours. The reaction mixture was cooled to 80 ° C. and diluted with ice water, and then made alkaline by adding 35% aqueous sodium hydroxide solution, and extracted successively with ether and chloroform. The organic extracts were combined and evaporated to dryness under reduced pressure. At this time, the remaining viscous oil was dissolved in ether, and the ethereal aqueous solution was washed with water. The aqueous wash was back-exteact with chloroform and the chloroform extract was mixed with ethereal solution. The combined organic solution was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residual oil was cooled to 78 ° C. and partially solidified. The semisolid thus obtained was diluted with a small amount of ether and filtered. The resulting solid was dissolved in a mixture of acetonitrile and chloroform, the solution was treated with activated carbon and filtered, and the filtrate was evaporated to dryness under reduced pressure. The resulting semisolid was diluted with a small amount of ether and cooled. The resulting solid was collected by filtration, washed with a small amount of cold ether and dried to give 84.6 g of 4- (heptylamino) pyridine with a melting point of 50-52 ° C.

C. 4-(헵틸아미노)피리딘은 또한 4-아미노피리딘과 헵타알데히드의 혼합물을 다음 실시예 10B의 방법에 따라 수소첨가시켜 제조할 수 있다.C. 4- (heptylamino) pyridine can also be prepared by hydrogenation of a mixture of 4-aminopyridine and heptaaldehyde following the method of Example 10B.

D. 4-(헵틸아미노)피리딘 10.0g(0.052몰)을 아세토니트릴 40g에 녹인 용액을 교반하고 가온한 후, 여기에 1,14-디브로모테트라데칸 9.3g(0.026몰)의 아세토니트릴(230ml)용액을 적가했다. 그결과 생긴 혼합물을 환류하에서 20시간 동안 가열했다. 반응 혼합물을 실온까지 냉각하여 침전된 생성물을 여과하여 모으고, 차가운 아세토니트릴로 세척한 후 건조하여 융점이 88-90℃인 1,14-비스-[4-(헵틸아미노)-1-피리디늄] 테트라데칸 디브로마이드 13.9g을 얻었다.D. A solution of 10.0 g (0.052 mol) of 4- (heptylamino) pyridine dissolved in 40 g of acetonitrile was stirred and warmed, followed by 9.3 g (0.026 mol) of acetonitrile (1,14-dibromotetradecane). 230 ml) was added dropwise. The resulting mixture was heated at reflux for 20 hours. The reaction mixture was cooled to room temperature, and the precipitated product was collected by filtration, washed with cold acetonitrile and dried to give 1,14-bis- [4- (heptylamino) -1-pyridinium] having a melting point of 88-90 占 폚. 13.9 g of tetradecane dibromide was obtained.

[실시예 2]Example 2

1,14-비스-[4-(헵틸아미노)-1-피리디늄] 테트라데칸 디브로마이드 5.0g의 메탄올(5.0ml)용액을, 메탄올내 충진된 클로라이드형의 합성 음이온 교환수지(앰버라이트 IRA400이란 상품명으로 롬 앤드 하아스사에 의해 판매) 500ml를 함유한 직경 3인치 컬럼 상층에 가하고, 125ml씩의 메탄올로 5번 용출했다. 용출액을 모아서 감압하에서 즐발 건조시키고, 잔류 기름을 에탄올에 재용해시킨 후, 활성탄으로 처리하고 증발건조시켰다. 잔류한 고체를 몇 방울의 아세토니트릴을 함유한 에테르로 연화하고, 여과하여 모은 후 진공하의 오산화인 상에서 건조시켜, 융점 113-116℃인 1,14-비스-[4-(헵틸아미노)-1-피리디늄] 테트라데칸 3.94g을 얻었다.A chloride (5.0 ml) solution of 5.0 g of 1,14-bis- [4- (heptylamino) -1-pyridinium] tetradecane dibromide was prepared using a chloride-type synthetic anion exchange resin (Amberlite IRA400) The product was added to the upper layer of a 3-inch diameter column containing 500 ml of a product sold by Rohm and Haas, and eluted five times with 125 ml of methanol each. The eluate was collected and dried dry under reduced pressure, the residual oil was redissolved in ethanol, treated with activated charcoal and evaporated to dryness. The remaining solid was triturated with ether containing a few drops of acetonitrile, collected by filtration and dried over phosphorus pentoxide under vacuum to give 1,14-bis- [4- (heptylamino) -1 having a melting point of 113-116 ° C. -Pyridinium] 3.94 g of tetradecane was obtained.

[실시예 3]Example 3

4-(헵틸아미노)피리딘 11.54g(0.06몰)의 아세토니트릴(75ml) 현탁액을 교반시킨 후, 맑은 균질한 용액이 형성될 때까지 환류하에서 가열했다. 이어, 이 맑은 용액에 1,12-디브로모도데칸 9.84g(0.03몰)을 함유한 가온한 아세토데트릴(75ml) 용액을 적가했다. 첨가가 끝난 후 18시간 동안 환류하에 가열했다. 실온까지 냉각한 후 반응 혼합물을 감압하에서 증발 건조시켰다. 잔류 고체를 에테르에 슬러리하고 여과하여 모은 후, 60℃ 진공하에서 48시간 동안 건조시켜, 융점 101-103℃인 1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디브로마이드 21.1g을 얻었다.11.54 g (0.06 mol) of acetonitrile (75 ml) suspension of 4- (heptylamino) pyridine was stirred and then heated under reflux until a clear homogeneous solution was formed. To this clear solution was then added dropwise a warmed acetodetril (75 ml) solution containing 9.84 g (0.03 mol) of 1,12-dibromododecane. After the addition was heated under reflux for 18 hours. After cooling to room temperature the reaction mixture was evaporated to dryness under reduced pressure. The residual solid was slurried in ether, filtered and collected and dried under vacuum at 60 ° C. for 48 hours to give 1,12-bis- [4- (heptylamino) -1-pyridinium] dodecane di having a melting point of 101-103 ° C. 21.1 g of bromide was obtained.

[실시예 4]Example 4

A. 1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디브로마이드 6.6g의 메탄올(25ml) 용액을, 메탄올내 클로라이드 형의 합성음이온 교환수지(앰벌라이트 IRA 400 이란 상품명하에 롬 앤드 하아스사에 의해 판매) 1ℓ로 충진된 직경 3인치의 컬럼 상층에 가하고, 700ml의 용출액이 모아질 때까지 100ml씩의 메탄올로 서서히 용출시켰다. 용출액을 모아 25℃이하에서 감압하에 건조시켰다. 잔류 고무질을 에테르와 아세토니트릴 6:1의 혼합물로 반복하여 연화하고, 진공하에 건조시켜, 융점 109-112℃의 1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디클로라이드 5.0g를 얻었다.A. A solution of 6.6 g of 1,12-bis- [4- (heptylamino) -1-pyridinium] dodecane dibromide in methanol (25 ml) was prepared using a synthetic anion exchange resin of chloride type in methanol. The product was added to a 3-inch diameter column top layer filled with 1 L), and sold slowly by 100 ml of methanol until 700 ml of eluate was collected. The eluate was collected and dried under reduced pressure at 25 ° C. or lower. The residual rubber is repeatedly softened with a mixture of ether and acetonitrile 6: 1 and dried under vacuum to give 1,12-bis- [4- (heptylamino) -1-pyridinium] dodecane at a melting point of 109-112 ° C. 5.0 g of dichloride were obtained.

B. 다른 방법으로서, 4-(헤틸아미노)피리딘 76.8g(0.4몰)과 1,12-디클로로도데칸 47.8g(0.2몰)을 함유한 혼합물을 125-130℃에서 4시간 동안 가열했다. 조금 냉각시킨 후 아세토니트릴 300ml를 가하고, 생성된 혼합물을 증기욕 온도에서 가열하여 완전한 용액을 얻고, 이것을 밤새 냉장고에 보관했다. 침전된 생성물을 여과하여 모으고, 차가운 아세토니트릴과 에테트로 세척한 후, 흡습성 생성물을 즉시 진공건조시켜, 융점 112-115℃의 1,12-비스-[4-(헵틸아미노)-1-피리디늄] 도데칸 디클로라이드 112g을 얻었다.B. As another method, a mixture containing 76.8 g (0.4 mol) of 4- (hetylamino) pyridine and 47.8 g (0.2 mol) of 1,12-dichlorododecane was heated at 125-130 ° C. for 4 hours. After cooling slightly, 300 ml of acetonitrile were added and the resulting mixture was heated at steam bath temperature to obtain a complete solution which was stored overnight in the refrigerator. The precipitated product was collected by filtration, washed with cold acetonitrile and etet, and then the hygroscopic product was immediately dried in vacuo to give 1,12-bis- [4- (heptylamino) -1-pyrid at a melting point of 112-115 ° C. Dinium] 112 g of dodecane dichloride was obtained.

[실시예 5]Example 5

A. 4-브로모피리딘 하이드로클로라이드 100.0g(0.51몰)과 n-헵실아민 하이드로클로라이드 110g(0.8몰)의 혼합물을 유(油)욕에서 가열했다. 욕의 온도가 175-180℃로되어 반응 혼합물이 용융하기 시작했을 때, 교반을 시작했다. 이때 욕의 온도가 227℃로 되었으며, 계속 3.5시간 동안 교반했다. 실온까지 냉각한 후 반응 혼합물을 뜨거운 물에 녹이고, 결과 생긴 용액을 얼음으로 냉각한 후 묽은 수산화나트륨 수용액을 가하여 알칼리성으로 하고, 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황상나트륨 상에서 건조시키고 감압하에서 증발 건조시켰다. 잔사를 에테르로 연화한 후, 냉각시켰다. 결과 생긴 고체를 여과하여 모은 후, 차가운 에테르로 세척했다. 여액을 증발시켜 2차 고형 산물을 얻었다. 이것을 모아서 클로로포름에 용해시킨 후, 활성탄으로 처리하고 여과했다. 여액을 감압하에서 증발시키고, 잔사를 차가운 에테르와 함께 연화했다. 이렇게 얻은 생성물을 여과하여 모으고, 차가운 에테르로 세척한 후 건조시켜서, 융점 66-68℃의 4-(헥실아미노)피리딘 63.6g을 얻었다. 여액을 증발시켜 융점 65-67℃인 생성물 7.0g을 더 얻었다.A. A mixture of 100.0 g (0.51 mol) of 4-bromopyridine hydrochloride and 110 g (0.8 mol) of n-hepsylamine hydrochloride was heated in an oil bath. When the temperature of the bath reached 175-180 ° C. and the reaction mixture began to melt, stirring was started. At this time, the temperature of the bath was 227 ℃, and continued stirring for 3.5 hours. After cooling to room temperature, the reaction mixture was dissolved in hot water, the resulting solution was cooled with ice, diluted with aqueous sodium hydroxide solution, and made alkaline and extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue was triturated with ether and then cooled. The resulting solid was collected by filtration and washed with cold ether. The filtrate was evaporated to give a secondary solid product. This was collected, dissolved in chloroform, treated with activated carbon and filtered. The filtrate was evaporated under reduced pressure and the residue was triturated with cold ether. The product thus obtained was collected by filtration, washed with cold ether and dried to give 63.6 g of 4- (hexylamino) pyridine with a melting point of 66-68 ° C. The filtrate was evaporated to afford 7.0 g more product having a melting point of 65-67 ° C.

B. 다른 방법으로서, 4-(헥실아미노)피리딘을 다음의 방법으로 제조했다. 즉, N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드 229g(1몰)과 n-헥실아민 하이드로클로라이드 207g(1.5몰)의 혼합물을 교반하고 175-185℃에서 1.75시간 동안 가열했다. 반응물을 냉각시킨 후 얼음물 750ml로 희석했다. 결과 생긴 용액을 35% 수산화나트륨 수용액을 가하여 알칼리성으로 한 후, 물 1ℓ로 한번 더 희석하고, 에테르 및 디클로로메탄으로 추출했다. 유기 추출물을 모아 무수 황산나트륨 상에서 건조시킨 후 감압하에서 증발 건조시켰다. 잔사를 에테르로 결정화하고 클로로포름에 재용시킨 후, 결과 생긴 용액을 활성탄으로 처리하고 여과했다. 여액을 감압하에서 증발 건조시키고, 잔사를 에테르와 아세토니트릴의 혼합물로 연화했다. 이렇게 얻은 고체를 클로로포름에 재용시켜, 생긴 용액을 활성탄으로 처리하고 여과했다. 여액을 감압하에서 증발 건조시키고, 잔사를 차가운 에테르로 연화하여, 융점 68-70℃의 4-(헥실아미노)피리딘 71.0g을 얻었다.B. As another method, 4- (hexylamino) pyridine was prepared by the following method. That is, a mixture of 229 g (1 mol) of N- (4-pyridyl) pyridinium chloride hydrochloride and 207 g (1.5 mol) of n-hexylamine hydrochloride was stirred and heated at 175-185 ° C. for 1.75 hours. The reaction was cooled and diluted with 750 ml of ice water. The resulting solution was made alkaline by adding 35% aqueous sodium hydroxide solution, and then diluted once more with 1 L of water and extracted with ether and dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate and then evaporated to dryness under reduced pressure. The residue was crystallized with ether and redissolved in chloroform, and the resulting solution was treated with activated carbon and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was triturated with a mixture of ether and acetonitrile. The solid thus obtained was reused in chloroform, and the resulting solution was treated with activated carbon and filtered. The filtrate was evaporated to dryness under reduced pressure, and the residue was triturated with cold ether to give 71.0 g of 4- (hexylamino) pyridine with a melting point of 68-70 占 폚.

C. 4-(헥실아미노)피리딘 10.7g(0.6몰)의 아세토니트릴(50ml) 용액을 가온하고 교반한 후, 여기에 1,14-디브로모테트라데칸 10.7g(0.03몰)의 아세토니트릴(250ml) 용액을 적가한 후, 반응 혼합물에 환류하에서 22시간 동안 가열했다. 반응물을 감압하에서 증발 건조시키고, 잔류 고체를 아세토니트릴에 녹인 후, 생긴 용액을 활성탄으로 처리하고 여과했다. 여액을 감압하에서 증발 건조시키고, 결과 얻은 기름을 아세토니트릴로 결정화 했다. 생성물을 여과하여 모으고, 70℃/0.1mm에서 48시간 동안 건조시켜, 융점 91-93℃인 1,14-비스-[4-(헥실아미노)-1-피리디늄] 데트라데칸 디브로마이드 13.4g을 얻었다.C. A solution of 10.7 g (0.6 mole) of acetonitrile (50 ml) of 4- (hexylamino) pyridine is warmed and stirred, followed by 10.7 g (0.03 mole) of acetonitrile (1,14-dibromotetradecane). 250 ml) was added dropwise, and the reaction mixture was heated at reflux for 22 hours. The reaction was evaporated to dryness under reduced pressure, the residual solid was dissolved in acetonitrile, and the resulting solution was treated with activated charcoal and filtered. The filtrate was evaporated to dryness under reduced pressure and the resulting oil was crystallized from acetonitrile. The product was collected by filtration and dried for 48 hours at 70 ° C./0.1 mm to give 13.4 g of 1,14-bis- [4- (hexylamino) -1-pyridinium] dedecadecan dibromide having a melting point of 91-93 ° C. Got.

[실시예 6]Example 6

1,14-비스-[4-(헥실아미노)-1-피리디늄] 테트라데칸 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 94-95℃인 상응하는 디클로라이드 4.33g을 얻었다.The reaction was carried out in a similar manner as in Example 2 except that 5.0 g of 1,14-bis- [4- (hexylamino) -1-pyridinium] tetradecane dibromide was used, and the corresponding melting point was 94-95 ° C. 4.33 g of dichloride were obtained.

[실시예 7]Example 7

4-(헥실아미노)피리딘 10.7g(0.06몰)과 1,12-디브로모도데칸 9.85g(0.03몰)을 사용한 것을 제외하고는 실시예 5C의 방법을 유사하게 반응시켜, 융점 122-124℃의 1,12-비스-[4-(헥실아미노)-1-피리디늄] 도데칸 디브로마이드 17.6g을 얻었다.Melting point 122-124 ° C. by analogous reaction of the method of Example 5C, except that 10.7 g (0.06 mol) of 4- (hexylamino) pyridine and 9.85 g (0.03 mol) of 1,12-dibromododecane were used. 17.6 g of 1,12-bis- [4- (hexylamino) -1-pyridinium] dodecane dibromide was obtained.

[실시예 8]Example 8

1,12-비스-[4-(헥실아미노)-1-피리디늄] 도데칸 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 86-88℃의 상응하는 디클로라이드 3.96g을 얻었다.Reaction was carried out in a similar manner as in Example 2, except that 5.0 g of 1,12-bis- [4- (hexylamino) -1-pyridinium] dodecane dibromide was used, corresponding to a melting point of 86-88 ° C. 3.96 g of dichloride were obtained.

[실시예 9]Example 9

A. N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드 183.3g(0.8몰)과 n-옥틸아민 하이드로클로라이드 162g(0.98몰)의 혼합물을 욕의 온도가 225-230℃(내부온도 188℃)가 될때까지 유욕에서 가열하고, 결과 생긴 액체를 그 온도에서 2.5시간 동안 교반했다. 반응 혼합물을 70℃로 냉각시키고 얼음물 1ℓ로 희석한 후, 35% 수산화나트륨 수용액을 가하여 알칼리성으로 만들고 클로로포름으로 추출했다. 클로로포름 추출물을 무수황산나트륨 상에서 건조시키고 활성탄으로 처리한 후, 진공하에서 증발 건조시켰다. 결과 생긴 기름을 -78℃로 냉각했다. 형성된 반고체를 에테르로 연화하고, 그 결과 얻어진 고체를 여과하여 모은 후, 차가운 에테르로 세척하고 건조했다. 여액으로 부터 2차 산물 10g을 얻었다. 이것을 합해서 클로로포름에 녹이고, 이어 활성탄으로 처리한 후 여과(3번 반목)하고, 클로로포름 용액을 감압하에서 증발 건조시켰다. 결과 생긴 고체를 에테르로 연화하고 냉각시킨 후, 여과하여 모으고 차가운 에테르-헥산으로 세척하여, 융점 62-63℃인 거의 무색의 4-(옥틴아미노)피리딘 63.3g을 얻었다.A. Mixture of 183.3 g (0.8 mole) of N- (4-pyridyl) pyridinium chloride hydrochloride and 162 g (0.98 mole) of n-octylamine hydrochloride, the bath temperature is 225-230 ° C. (internal temperature 188 ° C.) Heated in an oil bath until the resultant, and the resulting liquid was stirred at that temperature for 2.5 hours. The reaction mixture was cooled to 70 ° C. and diluted with 1 L of ice water, then made alkaline by addition of 35% aqueous sodium hydroxide solution and extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate, treated with activated charcoal and then evaporated to dryness in vacuo. The resulting oil was cooled to -78 deg. The semisolid formed was triturated with ether, the resulting solid was collected by filtration, washed with cold ether and dried. 10 g of secondary product was obtained from the filtrate. This was combined, dissolved in chloroform, treated with activated charcoal, filtered (banned 3 times), and the chloroform solution was evaporated to dryness under reduced pressure. The resulting solid was triturated with ether and cooled, then filtered and collected and washed with cold ether-hexane to give 63.3 g of a nearly colorless 4- (octinamino) pyridine with a melting point of 62-63 ° C.

B. 다른 방법으로서, 4-(옥틸아미노)피리딘을 다음의 방법으로 제조했다. 즉, 4-아미노피리딘 94g(1몰), 옥타알데히드 384g(3몰), 10% 탄소상 팔라듐 수소첨가 촉매 7g의 혼합물을 충분량의 무수 에탄올에 녹여 총용량 1.2ℓ로 하고, 초기 수소압 45psi, 70-90℃에서 4.5시간 동안 수소첨가시켰다. 혼합물을 냉각시킨 후, 수소첨가촉매를 여과하여 제거하고 여액을 감압하에서 증발 건조시켰다. 잔류 기름을 정치(定置)하에 결정화하고, 고체 생성물을 헥산으로 연화한 후 여과하여 모으고, 새로운 핵산으로 세척하고 진공하 40℃에서 건조하여, 융점 70-73℃의 4-(옥틸아미노)피리딘 182g을 얻었다.B. As another method, 4- (octylamino) pyridine was prepared by the following method. That is, a mixture of 94 g (1 mol) of 4-aminopyridine, 384 g (3 mol) of octaaldehyde, and 7 g of 10% palladium hydrogenated catalyst on carbon was dissolved in a sufficient amount of anhydrous ethanol to a total capacity of 1.2 L, and the initial hydrogen pressure was 45 psi, 70 Hydrogenation at −90 ° C. for 4.5 hours. After cooling the mixture, the hydrogenation catalyst was removed by filtration and the filtrate was evaporated to dryness under reduced pressure. The residual oil is crystallized under standing, the solid product is triturated with hexane, filtered and collected, washed with fresh nucleic acid and dried at 40 ° C. in vacuo to give 182 g of 4- (octylamino) pyridine with a melting point of 70-73 ° C. Got.

C. 4-(옥틸아미노)피리딘 10.0g(0.049몰)의 아세토니트릴 (15ml)용액을 가온하고 교반한 후, 여기에 1,10-디브로모데칸 7.4g(0.0245몰)의 아세토니트릴(50ml) 용액을 적가하고, 결과 생긴 혼합물을 환류하에서 18시간 동안 가열했다. 이 혼합물을 실온에서 1시간 동안 냉각하고 교반한 후, 침전된 고체를 여과하여 모으고 아세토니트릴로 세척한 후 85℃에서 48시간 건조시켜, 융점 163-164℃의 1,10-비스-[4-(옥틸아미노)-1-피리디늄] 데칸 디브로마이드 15.6g을 얻었다.C. Warm and stir 10.0 g (0.049 mol) of acetonitrile (15 ml) solution of 4- (octylamino) pyridine, and add 7.4 g (0.0245 mol) of acetonitrile (50 ml) of 1,10-dibromodecane. ) Was added dropwise and the resulting mixture was heated at reflux for 18 h. After cooling the mixture for 1 hour at room temperature and stirring, the precipitated solids were collected by filtration, washed with acetonitrile and dried at 85 ° C. for 48 hours to give 1,10-bis- [4- at a melting point of 163-164 ° C. (Octylamino) -1-pyridinium] decane dibromide 15.6 g was obtained.

[실시예 10]Example 10

A. 1,10-비스-[4-(옥틸아미노)-1-피리디늄] 데칸 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 213-214℃인 상응하는 디클로라이드 4.31g을 얻었다.A. Reaction was carried out in a similar manner as in Example 2, except that 5.0 g of 1,10-bis- [4- (octylamino) -1-pyridinium] decane dibromide was used, corresponding to a melting point of 213-214 ° C. 4.31 g of dichloride were obtained.

B. 다른 방법으로서, 4-(옥틸아미노)피리딘 6.8g과 1,10-디클로로데칸 31.5g의 혼합물을 교반하고 120℃까지 서서히 가열했다. 열원을 제거하였을 때, 발열 반응에 의해 온도가 180℃로 상승됐다. 반응 혼합물이 결정화되기 시작하는 순간 N,N-디메틸포름아미드 250ml를 급속히 가하고, 결과 생긴 혼합물을 가열하여 맑고 균질한 용액을 얻은 후 0℃로 냉각했다. 침전된 생성물을 여과하여 모으고 에테르로 세척한 후, 진공하 60℃에서 24시간 동안 건조시켜, 융점 215-217℃인 1,10-비스-[4-(옥틸아미노)-1-피리디늄] 데칸 디클로라이드 73g을 얻었다.B. As another method, a mixture of 6.8 g of 4- (octylamino) pyridine and 31.5 g of 1,10-dichlorodecane was stirred and heated slowly to 120 ° C. When the heat source was removed, the temperature rose to 180 ° C. due to the exothermic reaction. As soon as the reaction mixture began to crystallize, 250 ml of N, N-dimethylformamide was added rapidly, and the resulting mixture was heated to obtain a clear homogeneous solution and then cooled to 0 ° C. The precipitated product was collected by filtration and washed with ether and then dried in vacuo at 60 ° C. for 24 hours to give 1,10-bis- [4- (octylamino) -1-pyridinium] decan with a melting point of 215-217 ° C. 73 g of dichloride were obtained.

[실시예 11]Example 11

4-(옥틸아미노)피리딘 11.1g(0.054몰)과 1,8-디브로모옥탄 7.34g(0.027몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시키고 이 방법에서 반응 혼합물의 환류 시간을 6시간으로 하여, 융점 174-175℃의 1, 8-비스-[4-(옥틸아미노)-1-피리디늄] 옥탄 디브로마이드 1.56g을 얻었다.The reaction was carried out in a similar manner as in Example 9C, except that 11.1 g (0.054 mol) of 4- (octylamino) pyridine and 7.34 g (0.027 mol) of 1,8-dibromooctane were used. The reflux time was 6 hours to obtain 1.56 g of 1,8-bis- [4- (octylamino) -1-pyridinium] octane dibromide at a melting point of 174-175 ° C.

[실시예 12]Example 12

1, 8-비스-[4-(옥틸아미노)-1-피리디늄] 옥탄 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 210-211℃인 상응하는 디클로라이드 4.30g을 얻었다.Reaction was carried out in a similar manner as in Example 2 except that 5.0 g of 1,8-bis- [4- (octylamino) -1-pyridinium] octane dibromide was used, and the corresponding di 4.30 g of chloride were obtained.

[실시예 13]Example 13

4-(옥틸아미노)피리딘 11.1g(0.054몰)과 1,6-디브로모헥산6.6g(0.027몰)을 사용하고 반응 혼합물을 환류하에서 9시간 동안 가열한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 136-138℃인 1,6-비스-[4-(옥틸아미노)-1-피리디늄] 헥산 디브로마이드 15.1g을 얻었다.In Example 9C, except that 11.1 g (0.054 mol) of 4- (octylamino) pyridine and 6.6 g (0.027 mol) of 1,6-dibromohexane were used and the reaction mixture was heated at reflux for 9 hours. The reaction was carried out in a similar manner to give 15.1 g of 1,6-bis- [4- (octylamino) -1-pyridinium] hexane dibromide having a melting point of 136-138 ° C.

[실시예 14]Example 14

1,6-비스-[4-(옥틸아미노-1-피리디늄] 헥산 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 189-191℃인 상응하는 디클로라이드 4.23을 얻었다.Reaction was carried out in a similar manner as in Example 2, except that 5.0 g of 1,6-bis- [4- (octylamino-1-pyridinium] hexane dibromide was used, and the corresponding dichloride having a melting point of 189-191 ° C. 4.23 was obtained.

[실시예 15]Example 15

4-(옥틸아미노)피리딘 2.06g(0.01몰)의 아세토니트릴(15ml) 용액을 가온하고, 교반한 후, 여기에 1,6-헥산디올 디메탄설포네이트 1.37g(0.005몰)의 아세토니트릴 용액을 적가하고, 결과 생긴 혼합물을 환류하에서 20시간 동안 가열했다. 반응 혼합물을 감압하에서 증발건조시키고, 잔류 고무질을 에테르로 연화하여 무색의 흡습성 고체를 얻었다. 이 고체를 에탄올, 벤젠 및 아세토니트릴의 혼합물에 재용해시키고, 결과 생신 용액을 감압에서 증발 건조시켰다. 잔사를 에테르로 연화하고, 결과 생긴 흰색 고체를 여과하여 빨리 모은후 무수에테르로 세척하고 28℃/0.1mm에서 72시간 동안 건조시켜, 왁스 상태의 흰색 고체인 1,6-비스-[4-(옥틸아미노)-1-피리디늄] 헥산 디메탄설포네이트 2.65g을 얻었다.2.06 g (0.01 mol) of acetonitrile (15 ml) solution of 4- (octylamino) pyridine is warmed and stirred, followed by 1.37 g (0.005 mol) of acetonitrile solution of 1,6-hexanediol dimethanesulfonate. Was added dropwise and the resulting mixture was heated at reflux for 20 h. The reaction mixture was evaporated to dryness under reduced pressure and the residual rubber was triturated with ether to give a colorless hygroscopic solid. This solid was redissolved in a mixture of ethanol, benzene and acetonitrile and the resulting fresh solution was evaporated to dryness under reduced pressure. The residue was triturated with ether, the resulting white solid was collected by filtration, washed quickly with anhydrous ether and dried at 28 ° C./0.1 mm for 72 hours to give a waxy white solid of 1,6-bis- [4- ( Octylamino) -1-pyridinium] 2.65 g of hexane dimethanesulfonate was obtained.

[실시예 16]Example 16

4-(헥실아미노)피리딘 14.24g(0.08몰)과 1,4-디브로모부탄 8.64g(0.04몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시키고, 이때 얻은 조잡한 생성물을 아세토니트릴과 아세톤의 혼합물로 연화하여, 융점 199-201℃의 1,4-비스-[4-(헥실아미노)-1-피리디늄] 부탄 디브로마이드 20.45g을 얻었다.The crude product obtained was reacted in a similar manner as in Example 9C, except that 14.24 g (0.08 mol) of 4- (hexylamino) pyridine and 8.64 g (0.04 mol) of 1,4-dibromobutane were used. The mixture was triturated with a mixture of acetonitrile and acetone to obtain 20.45 g of 1,4-bis- [4- (hexylamino) -1-pyridinium] butane dibromide at a melting point of 199-201 占 폚.

[실시예 17]Example 17

4-(헥실아미노)피리딘 10.7g(0.06몰)과 1,6-디브로모헥산 7.23g(0.03몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시키고, 이때 얻은 조잡한 생성물을 에테르, 아세토니트릴과 아세톤의 혼합물로 연화하여, 융점 178-178℃의 1,6-비스-[4-(헥실아미노)-1-피리디늄] 부탄 디브로마이드 14.90g을 얻었다.The crude product was reacted in a similar manner as in Example 9C, except that 10.7 g (0.06 mol) of 4- (hexylamino) pyridine and 7.23 g (0.03 mol) of 1,6-dibromohexane were reacted. The mixture was triturated with a mixture of ether, acetonitrile and acetone to obtain 14.90 g of 1,6-bis- [4- (hexylamino) -1-pyridinium] butane dibromide at a melting point of 178-178 ° C.

[실시예 18]Example 18

4-(헥실아미노)피리딘 10.7g(0.06몰)과 1,7-디브로모헵탄 7.75g(0.03몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시키고, 이때 얻은 조잡한 생성물을 아세토니트릴과 아세톤의 혼합물로 연화하여, 융점 157-158℃의 1,7-비스-[4-(헥실아미노)-1-피리디늄] 부탄 디브로마이드 16.4g을 얻었다.The crude product obtained was reacted in a similar manner as in Example 9C, except that 10.7 g (0.06 mol) of 4- (hexylamino) pyridine and 7.75 g (0.03 mol) of 1,7-dibromoheptane were used. The mixture was triturated with acetonitrile and acetone to give 16.4 g of 1,7-bis- [4- (hexylamino) -1-pyridinium] butane dibromide at a melting point of 157-158 占 폚.

[실시예 19]Example 19

4-(헥실아미노)피리딘 10.7g(0.06몰)과 1,9-디브로모난 8.6g(0.03몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 114-115℃의 1,9-비스-[4-(헥실아미노)-1-피리디늄] 노난 디브로마이드 17.15g을 얻었다.The reaction was carried out in a similar manner as in Example 9C, except that 10.7 g (0.06 mol) of 4- (hexylamino) pyridine and 8.6 g (0.03 mol) of 1,9-dibromonane were used, and the melting point was 114-115 ° C. 17.15 g of 1,9-bis- [4- (hexylamino) -1-pyridinium] nonane dibromide was obtained.

[실시예 20]Example 20

4-(헵틸아미노)피리딘 15.4g(0.08몰)과 1,4-디브로모부탄 8.64g(0.04몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 229-230℃의 1,4-비스-[4-(헵틸아미노)-1-피리디늄] 부탄 디브로마이드 23.1g을 얻었다.Melting point 229-230 ° C by reaction in a similar manner as in Example 9C, except that 15.4 g (0.08 mol) of 4- (heptylamino) pyridine and 8.64 g (0.04 mol) of 1,4-dibromobutane were used. 23.1 g of 1,4-bis- [4- (heptylamino) -1-pyridinium] butane dibromide was obtained.

[실시예 21]Example 21

4-(헵틸아미노)피리딘 10.0g(0.052몰)과 1,7-디브로모부탄 6.7g(0.026몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 142-143℃의 1,7-비스-[4-(헵틸아미노)-1-피리디늄] 헵탄 디브로마이드 14.05g을 얻었다.Melting point 142-143 ° C. by reaction in a similar manner as in Example 9C, except that 10.0 g (0.052 mol) of 4- (heptylamino) pyridine and 6.7 g (0.026 mol) of 1,7-dibromobutane were used. 14.05 g of 1,7-bis- [4- (heptylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 22]Example 22

4-(헵틸아미노)피리딘 11.6g(0.06몰)과 1,8-디브로모옥탄 8.2g(0.03몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시키고 아세토니트릴-에테르로 재결정화시켜, 융점 161-162℃의 1,8-비스-[4-(헵틸아미노)-1-피리디늄] 옥탄 디브로마이드 18.6g을 얻었다.The reaction was carried out in a similar manner as in Example 9C, except that 11.6 g (0.06 mol) of 4- (heptylamino) pyridine and 8.2 g (0.03 mol) of 1,8-dibromooctane were recrystallized from acetonitrile-ether. The mixture was obtained to obtain 18.6 g of 1,8-bis- [4- (heptylamino) -1-pyridinium] octane dibromide at a melting point of 161-162 ° C.

[실시예 23]Example 23

1,8-비스-[4-(헵틸아미노)-1-피리디늄] 옥탄 디브로마이드 5.0g(0.0076몰)을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 206-208℃인 상응하는 디클로라이드 4.1g을 얻었다.Melting point 206-208 ° C by reaction in a similar manner as in Example 2, except that 5.0 g (0.0076 mol) of 1,8-bis- [4- (heptylamino) -1-pyridinium] octane dibromide was used 4.1 g of phosphorous dichloride was obtained.

[실시예 24]Example 24

4-(헵디아미노)피리딘 15.4g(0.08몰)과 1,9-디브로모난 11.44g을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 115-116℃의 1,9-비스-[4-(헵틸아미노)-1-피리디늄] 노난 디브로마이드 21.3g을 얻었다.The reaction was carried out in a similar manner as in Example 9C, except that 15.4 g (0.08 mole) of 4- (hepdiamino) pyridine and 11.44 g of 1,9-dibromonan were used, and 1,9 at a melting point of 115-116 ° C. 21.3 g of -bis- [4- (heptylamino) -1-pyridinium] nonane dibromide was obtained.

[실시예 25]Example 25

1,9-비스-[4-(헵틸아미노)-1-피리디늄] 노난 디브로마이드 5.0g(0.0075몰)을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 154-155℃인 상응하는 디클로라이드 4.2g을 얻었다.Reaction was carried out in a similar manner as in Example 2, except that 5.0 g (0.0075 mol) of 1,9-bis- [4- (heptylamino) -1-pyridinium] nonane dibromide was used, and the melting point was 154-155 ° C. 4.2 g of phosphorous dichloride was obtained.

[실시예 26]Example 26

4-(헵틸아미노)피리딘 15.4g(0.08몰)과 1,10-디브로모데칸 12.0g(0.04몰)을 사용한 것을 제외하고는 실시예 9C에서와 유사한 방법으로 반응시켜, 융점 163-165℃의 1,10-비스-[4-(헵틸아미노)-1-피리디늄] 테칸 디브로마이드 25.7g을 얻었다.Melting point 163-165 ° C by reaction in a similar manner as in Example 9C, except that 15.4 g (0.08 mole) of 4- (heptylamino) pyridine and 12.0 g (0.04 mole) of 1,10-dibromodecane were used. 25.7 g of 1,10-bis- [4- (heptylamino) -1-pyridinium] decane dibromide was obtained.

[실시예 27]Example 27

1,10-비스-[4-(헵틸아미노)-1-피리디늄] 데칸 디브로마이드 5.0g(0.0073몰)을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 209-210℃인 상응하는 디클로라이드 4.35g을 얻었다.Reaction was carried out in a similar manner as in Example 2, except that 5.0 g (0.0073 mol) of 1,10-bis- [4- (heptylamino) -1-pyridinium] decane dibromide was used, and the melting point was 209-210 ° C. 4.35 g of phosphorous dichloride were obtained.

[실시예 28]Example 28

물 150ml내의 하이드록사이드 형의 합성음이온 교환수지(엠버라이트 IRA400이란 상품명으로 롬 앤드 하아스사에 의해 판매)를 교반시킨 슬러리 30ml에 혼합물이 산성이 될 때까지 48%의 플루오르화수소 산수용액을 적가했다. 0.5시간 더 교반한 후, 슬러리를 컬럼에 넣었다. 컬럼을 유출시키고, 48%의 플루오르화수소산 15ml를 함유한 증류수 185ml 용액으로 수지를 세척 했다. 이어 수지를 용출액이 약산성이 될때까지 증류수로 세척하고, 이어 20%, 40% 및 50% 수성메탄올의 순서로 세척한 다음, 용출액이 중성으로 될 때까지 무수 메탄올로 최종 세척했다. 플루오라이드형의 이온교환 수지 컬럼 상층에 1,10-비스-[4-(헵틸아미노)-1-피리디늄] 데칸 디브로마이드 0.25g(0.000365몰)을 함유한 메탄올 용액 1ml를 가했다. 각각 15ml씩 5개의 분획물을 모았다. 처음 3개의 분획물을 오마서 감압하에서 증발 건조시켰다. 기름상 잔사를 톨루엔과 에탄올의 혼합물에 용해시키고, 결과 생긴 용액을 감압하에서 증발 건조시켰다. 잔류 기름을 벤젠과 아세톤의 혼합물에 재용해시키고, 용액을 농축시켜 수량을 했다. 분리된 고체를 여과하여 모으고 24℃/0.1mm에서 24시간 건조시켜, 융점 85-90℃인 불순한 1,10-비스-[4-(헵틸아미노)-1-피리디늄] 데칸 디플루오라이드 0.11g을 얻었다Hydrogen fluoride aqueous solution (48%) was added dropwise to 30 ml of a stirred slurry of a hydroxide-type synthetic anion exchange resin (sold under the trade name Amberlite IRA400) in 150 ml of water until the mixture became acidic. . After stirring for an additional 0.5 hours, the slurry was placed in a column. The column was drained and the resin washed with 185 ml of distilled water containing 15 ml of 48% hydrofluoric acid. The resin was then washed with distilled water until the eluate became weakly acidic, followed by 20%, 40% and 50% aqueous methanol, followed by a final wash with anhydrous methanol until the eluent became neutral. 1 ml of a methanol solution containing 0.25 g (0.000365 mol) of 1,10-bis- [4- (heptylamino) -1-pyridinium] decane dibromide was added to the upper layer of the fluoride ion exchange resin column. Five fractions of 15 ml each were collected. The first three fractions were evaporated to dryness under reduced pressure. The oily residue was dissolved in a mixture of toluene and ethanol and the resulting solution was evaporated to dryness under reduced pressure. The residual oil was redissolved in the mixture of benzene and acetone and the solution was concentrated to yield. The separated solids were collected by filtration and dried for 24 hours at 24 ° C./0.1 mm to give 0.11 g of impure 1,10-bis- [4- (heptylamino) -1-pyridinium] decane difluoride having a melting point of 85-90 ° C. Got

[실시예 29].Example 29.

A. N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드 115g(0.5몰)과 n-노닐아민 하이드로클로라이드 119g(0.66몰)의 고형 혼합물을 욕의 온도가 220℃(내부온도 190-194℃)로 될때까지 유욕내에서 가열하고, 결과 생긴 액체를 이 온도에서 2시간 동안 교반시켰다. 반응 혼합물을 80℃로 냉각하고, 얼음물 1.2ℓ로 희석한 후, 35% 수산화나트륨 수용액을 가하여 알칼리성으로 하고 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황산나트륨상에서 건조시키고 활성탄으로 처리한 후, 여과하여 감압하에서 증발 건조시켰다. 잔류한 점성이 있는 기름을 -78℃로 냉각하고, 에테르로 연화시켰다. 결과 생긴 고체를 여과하여 모으고 차가운 에테르로 세척했다. 여액으로 부터 2차 고형 산물을 얻었다. 이것을 모아 클로로포름에 재용해시키고, 결과 생긴 용액을 활성탄으로 처리한 후 여과했다. 이것을 한번 더 반복하고, 여액을 감압하에서 증발 건조시켰다. 잔류 반고체를 에테르로 연화하고 냉각하여 거의 무색의 고체를 얻고, 이것을 여과하여 모은 후 차가운 에테르로 세척, 건조했다. 고체를 클로로포름에 용해시키고, 결과 생긴 용액을 활성탄으로 처리하고 여과한 후 감압하에서 증발 건조시켰다. 결과 얻어진 반고체를 냉각하고 에테르로 연화하여 무색의 고체를 얻고, 이것을 여과하여 모은 후 차가운 에테르로 세척하고 건조시켜 융점 59-60℃인 4-(노닐아미노)피리딘 51.7을 얻었다. 여액으로 부터 융점 55-57℃인 2차 산물 11.6g을 더 얻었다.A. A solid mixture of 115 g (0.5 mole) of N- (4-pyridyl) pyridinium chloride hydrochloride and 119 g (0.66 mole) of n-nonylamine hydrochloride was prepared at a bath temperature of 220 ° C. (internal temperature 190-194 ° C.). The resulting liquid was heated in an oil bath until the resulting mixture was stirred at this temperature for 2 hours. The reaction mixture was cooled to 80 ° C., diluted with 1.2 liters of ice water, and then made alkaline by adding 35% aqueous sodium hydroxide solution and extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate, treated with activated charcoal, filtered and evaporated to dryness under reduced pressure. The remaining viscous oil was cooled to -78 ° C and triturated with ether. The resulting solid was collected by filtration and washed with cold ether. A second solid product was obtained from the filtrate. This was collected, redissolved in chloroform, and the resulting solution was treated with activated carbon and filtered. This was repeated once more and the filtrate was evaporated to dryness under reduced pressure. The remaining semisolid was triturated with ether and cooled to give an almost colorless solid, which was collected by filtration, washed with cold ether and dried. The solid was dissolved in chloroform and the resulting solution was treated with activated carbon, filtered and evaporated to dryness under reduced pressure. The resulting semisolid was cooled and triturated with ether to give a colorless solid, which was collected by filtration, washed with cold ether and dried to give 5- (nonylamino) pyridine 51.7 having a melting point of 59-60 ° C. Further obtained 11.6 g of a secondary product having a melting point of 55-57 ° C. from the filtrate.

B. 다른 방법으로서, 4-(노닐아미노)피리딘을 다음과 같이 제조했다. 즉, 4-(아미노피리딘 39.5g(0.42몰), 노닐알데히드 175g(1.24몰)과 10% 탄소상 팔라듐 수소첨가 촉매 5.0g의 혼합물에 무수 에탄올을 충분량 가하여 총용량 600ml로 한 용액을 가온하고, 초기 수소압 45psi하에서 수소흡수가 끝날 때까지 수소첨가시켰다. 반응 혼합물을 여과하여 촉매를 제거하고, 여액을 감압하에서 증발 건조시켰다. 잔류 기름을 진공 증류시켜, 생성되었을 수도 있는 노닐 알콜을 제거했다. 비점 63-64℃/4.5mm의 분획물을 수거하여 두고, 잔사를 에테르로 연화한 후 -78℃로 냉각시켰다. 침전된 고체를 여과하여 모으고, 차가운 에테르로 세척했다. 이생성물을 클로로포름에 용해시키고, 겨로가 생긴 용액을 활성탄으로 처리한 후 여과하고, 여액을 증발 건조시켰다. 자사를 에테르로 연화하고, -78℃로 냉각했다. 얻어진 고체를 여과하여 모으로 차가운 에테르로 세척한 후 공기중에서 건조시켜, 융점 57-59℃인 4-(노닐아미노)피리딘 27.0g을 얻었다.B. As another method, 4- (nonylamino) pyridine was prepared as follows. That is, a solution of 4- (aminopyridine 39.5 g (0.42 mole), nonylaldehyde 175 g (1.24 mole) and 5.0 g of 10% carbonaceous palladium hydrogenation catalyst was added with anhydrous ethanol in sufficient amount to warm the solution to a total capacity of 600 ml. The hydrogenation was carried out at 45 psi hydrogen pressure until the end of hydrogen absorption, the reaction mixture was filtered to remove the catalyst, the filtrate was evaporated to dryness under reduced pressure and the residual oil was distilled under vacuum to remove any nonyl alcohol which may have been produced. Fractions of 63-64 ° C./4.5 mm were collected and the residue was triturated with ether and cooled to −78 ° C. Precipitated solids were collected by filtration and washed with cold ether The product was dissolved in chloroform, The resulting solution was treated with activated charcoal, filtered and the filtrate was evaporated to dryness, the mixture was triturated with ether and cooled to -78 ° C. After washing with ether and drying in air, 27.0 g of 4- (nonylamino) pyridine having a melting point of 57-59 占 폚 was obtained.

C. 4-(노닐아미노)피리딘 11.0g(0.05몰)의 아세토니트릴(150ml) 현탁액을 교반하고, 맑고 균질한 용액이 얻어질 때까지 가온했다. 이 맑은 용액에 1,8-디브로모옥탄 6.9g(0.025몰)의 아세토니트릴(50ml)용액을 적가하고, 결과 생긴 혼합물을 용액으로 부터 고체가 침전될 때까지 환류하에서 19시간 동안 가열했다. 이것을 냉각시킨 후 고체를 여과하여 모으고, 에탄올에 재용해시켜 얻은 용액은 활성탄으로 처리한 후 여과하고, 감압하에서 증발 건조시켰다. 잔류 기름을 소량의 아세토니트릴을 함유한 에테르로 연화하여 무색의 결정성 고체를 얻고, 이것을 여과하여 모은 후 건조시켜, 융점 178-179℃인 1,8-비스-[4-(노닐아미노)-1-피리디늄] 옥탄 디브로마이드 15.5g을 얻었다.C. A suspension of 11.0 g (0.05 mol) of acetonitrile (150 ml) of 4- (nonylamino) pyridine was stirred and warmed until a clear and homogeneous solution was obtained. To this clear solution was added 6.9 g (0.025 mol) of acetonitrile (50 ml) of 1,8-dibromooctane solution dropwise, and the resulting mixture was heated under reflux for 19 hours until a solid precipitated from the solution. After cooling, the solid was collected by filtration, and the solution obtained by re-dissolving in ethanol was treated with activated carbon, filtered, and evaporated to dryness under reduced pressure. The residual oil was triturated with ether containing a small amount of acetonitrile to obtain a colorless crystalline solid, which was collected by filtration and dried to dry 1,8-bis- [4- (nonylamino)-with a melting point of 178-179 ° C. 1-pyridinium] octane dibromide 15.5 g was obtained.

[실시예 30]Example 30

4-(프로필아미노)피리딘 3.54g(0.026몰)과 1,10-디브로모데칸 3.90g(0.013몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 206-207℃인 1,10-비스-[4-(프로필아미노)-1-피리디늄] 데칸 디브로마이드 5.19g을 얻었다.Melting point 206-207 ° C by reaction in a similar manner as in Example 29C, except that 3.54 g (0.026 mol) of 4- (propylamino) pyridine and 3.90 g (0.013 mol) of 1,10-dibromodecane were used. 5.19 g of phosphorous 1,10-bis- [4- (propylamino) -1-pyridinium] decane dibromide was obtained.

[실시예 31]Example 31

4-(헥실아미노)피리딘 14.24g(0.08몰)과 1,5-디브로모펜탄 9.20g(0.04몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시키고 아세토니트릴-아세톤으로 재결정시켜,융점 155-156℃인 1,5-비스-[4-(헥실아미노)-1-피리디늄] 펜탄 디브로마이드 12.3g을 얻었다.The reaction was carried out in a similar manner as in Example 29C, except that 14.24 g (0.08 mol) of 4- (hexylamino) pyridine and 9.20 g (0.04 mol) of 1,5-dibromopentane were recrystallized from acetonitrile-acetone. 12.3 g of 1,5-bis- [4- (hexylamino) -1-pyridinium] pentane dibromide having a melting point of 155-156 占 폚 was obtained.

[실시예 32]Example 32

4-(헥실아미노)피리딘 10.7g(0.06몰)과 1,8-디브로모옥탄 8.2g(0.03몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 180-181℃인 1,8-비스-[4-(헥실아미노)-1-피리디늄] 옥탄 디브로마이드 16.3g을 얻었다.Melting point 180-181 ° C. by reaction in a similar manner as in Example 29C, except that 10.7 g (0.06 mol) of 4- (hexylamino) pyridine and 8.2 g (0.03 mol) of 1,8-dibromooctane were used. 16.3 g of phosphorous 1,8-bis- [4- (hexylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 33]Example 33

4-(헥실아미노)피리딘 12.5g(0.07몰)과 1,10-디브로모데탄 10.5g(0.035몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 148-149℃인 1,10-비스-[4-(헥실아미노)-1-피리디늄] 데칸 디브로마이드 16.0g을 얻었다.Melting point 148-149 ° C by reaction in a similar manner as in Example 29C, except that 12.5 g (0.07 mol) of 4- (hexylamino) pyridine and 10.5 g (0.035 mol) of 1,10-dibromodetane were used. 16.0 g of phosphorous 1,10-bis- [4- (hexylamino) -1-pyridinium] decane dibromide was obtained.

[실시예 34]Example 34

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,4-디브로모부탄 8.2g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 288-290℃인 1,4-비스-[4-(사이클로헥실아미노)-1-피리디늄] 옥탄 디브로마이드 18.2g을 얻었다.Melting point 288-290 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 8.2 g (0.038 mol) of 1,4-dibromobutane were used. 18.2 g of 1,4-bis- [4- (cyclohexylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 35]Example 35

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,5-디브로모펜탄 8.75g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 255-256℃인 1,5-비스-[4-(사이클로헥실아미노)-1-피리디늄] 옥탄 디브로마이드 19.0g을 얻었다.Melting point 255-256 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 8.75 g (0.038 mol) of 1,5-dibromopentane were used. 19.0 g of 1,5-bis- [4- (cyclohexylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 36]Example 36

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,6-디브로모옥탄 9.3g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 307-308℃인 1,6-비스-[4-(사이클로헥실아미노)-1-피리디늄] 헥산 디브로마이드 19.1g을 얻었다.Melting point 307-308 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 9.3 g (0.038 mol) of 1,6-dibromooctane were used. 19.1 g of 1,6-bis- [4- (cyclohexylamino) -1-pyridinium] hexane dibromide was obtained.

[실시예 37]Example 37

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,7-디브로모헵탄 9.8g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 311-313℃인 1,7-비스-[4-(사이클로헥실아미노)-1-피리디늄] 헵탄 디브로마이드 2.01g을 얻었다.Melting point 311-313 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 9.8 g (0.038 mol) of 1,7-dibromoheptane were used. 2.01 g of 1,7-bis- [4- (cyclohexylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 38]Example 38

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,8-디브로모옥탄 10.34g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 270-271℃인 1,8-비스-[4-(사이클로헥실아미노)-1-피리디늄] 옥탄 디브로마이드 16.3g을 얻었다.Melting point 270-271, by reacting in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 10.34 g (0.038 mol) of 1,8-dibromooctane were used. 16.3g of 1,8-bis- [4- (cyclohexylamino) -1-pyridinium] octane dibromide which is ° C was obtained.

[실시예 39]Example 39

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,9-디브로모노단 10.8g(0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 149-151℃인 1,9-비스-[4-(사이클로헥실아미노)-1-피리디늄] 노난 디브로마이드 16.3g을 얻었다.Melting point 149-151 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 10.8 g (0.038 mol) of 1,9-dibromonodan were used. 16.3g of 1,9-bis- [4- (cyclohexylamino) -1-pyridinium] nonane dibromide which is ° C was obtained.

[실시예 40]Example 40

4-(사이클로헥실아미노)피리딘 13.4g(0.076몰)과 1,10-디브로모옥탄11.4g (0.038몰)을 사용한 것을 제외하고는 실시예 29C에서와 유사한 방법으로 반응시켜, 융점 226-227℃인 1,10-비스-[4-(사이클로헥실아미노)-1-피리디늄] 헥산 디브로마이드 19.0g을 얻었다.Melting point 226-227 by reaction in a similar manner as in Example 29C, except that 13.4 g (0.076 mol) of 4- (cyclohexylamino) pyridine and 11.4 g (0.038 mol) of 1,10-dibromooctane were used. 19.0 g of 1,10-bis- [4- (cyclohexylamino) -1-pyridinium] hexane dibromide was obtained.

[실시예 41]Example 41

A. N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드 198.0g(1.33몰)과 2-에틸헥실아민 하이드로클로라이드 322g(2몰)의 혼합물을 215℃의 유욕에서 2시간 동안 교반하면서 가열했다. 혼합물을 60℃로 냉각하고, 물 500ml로 희석한 후, 얼음을 가해 냉각하고, 35% 수산화나트륨 수용액을 가하여 알칼리성으로 했다. 알칼리성 혼합물을 에테르로 추출하고, 에테르성 추출물을 무수 황산나트륨상에서 증류시켜 비점 145-150℃/0.9mm인 4-(2-에틸헥실아미노)피리딘 101.0g을 얻었다.A. A mixture of 198.0 g (1.33 mol) of N- (4-pyridyl) pyridinium chloride hydrochloride and 322 g (2 mol) of 2-ethylhexylamine hydrochloride was heated with stirring in an oil bath at 215 ° C. for 2 hours. The mixture was cooled to 60 ° C., diluted with 500 ml of water, cooled by addition of ice, and made alkaline by adding 35% aqueous sodium hydroxide solution. The alkaline mixture was extracted with ether and the etheric extract was distilled on anhydrous sodium sulfate to give 101.0 g of 4- (2-ethylhexylamino) pyridine having a boiling point of 145-150 ° C./0.9 mm.

B. 다른 방법으로서, 4-(2-에틸헥실아미노)피리딘을 다음과 같이 제조했다. 즉, 4-아미노피리딘 800g(8.4몰)과 트리에틸아민 150ml을 함유한 디클로로메탄(6.4ℓ) 용액을 교반하고, 여기에 2-에틸헥사노일 클로라이드 1610g(10.0몰)의 디클로로메탄 (1.6ℓ)용액을 3시간에 걸쳐 가했다. 첨가중의 온도는 15℃로 유지시켰다. 첨가가 끝난후 반응 혼합물을 증기욕에서 2시간 가온했다. 이 반응 혼합물을 냉각한 후, 반응 혼합물을 물로 완전히 세척하고 무수 황산 나트륨 상에서 건조시켰다. 이어 활성탄으로 처리하고 여과했다. 여액을 증발시켜 N-(4-피리딜)-2-에틸헥산아미드 1843g을 얻었다.B. As another method, 4- (2-ethylhexylamino) pyridine was prepared as follows. That is, a solution of dichloromethane (6.4 L) containing 800 g (8.4 mol) of 4-aminopyridine and 150 ml of triethylamine was stirred, and 1610 g (10.0 mol) of 2-ethylhexanoyl chloride was added thereto (1.6 L). The solution was added over 3 hours. The temperature during the addition was kept at 15 ° C. After the addition was completed, the reaction mixture was warmed in a steam bath for 2 hours. After cooling the reaction mixture, the reaction mixture was washed thoroughly with water and dried over anhydrous sodium sulfate. Then treated with activated carbon and filtered. The filtrate was evaporated to give 1843 g of N- (4-pyridyl) -2-ethylhexaneamide.

리튬 알미늄 하이드라이드 100g(2.63몰)을 함유한 2ℓ의 테트라하이드로푸란 혼합물에, 완만한 환류를 유지하기에 충분한 속도로, N-(4-피리딜)-2-에틸헥산아미드 570g(2.62몰)의 테트라하이드로푸란(4ℓ)용액을 가했다. 첨가가 끝났을 때(약 3시간), 반응 혼합물을 환류하에서 7시간동안 가열했다. 냉각한 후, 이 반응 혼합물을 물 100ml, 15% 수산화나트륨 수용액 100ml, 물 300ml의 순서로 처리했다. 여과하여 고형분을 제거하고, 감압하여서 여액으로 부터 용매를 제거했다. 잔류 기름을 모아 반복 공정에서의 생성물과 합하고 진공증류시켜, 비점 135-160℃/0.2mm인 4-(2-에틸헥산아미드)피리딘 837g을 얻었다.570 g (2.62 mol) of N- (4-pyridyl) -2-ethylhexanamide in a 2 liter tetrahydrofuran mixture containing 100 g (2.63 mol) of lithium aluminum hydride at a rate sufficient to maintain moderate reflux Tetrahydrofuran (4 L) solution was added. At the end of the addition (about 3 hours), the reaction mixture was heated under reflux for 7 hours. After cooling, the reaction mixture was treated with 100 ml of water, 100 ml of 15% aqueous sodium hydroxide solution, and 300 ml of water. The solid was removed by filtration, and the solvent was removed from the filtrate under reduced pressure. The residual oil was collected, combined with the product from the repeating process, and vacuum distilled to give 837 g of 4- (2-ethylhexaneamide) pyridine having a boiling point of 135-160 ° C / 0.2 mm.

C. 4-(2-에틸헥실아미노)피리딘 10.3g(0.05몰)의 아세토니트릴(50ml)용액을 가온하고 교반한 후, 여기에 1,12-디브로모도데칸 8.2g(0.025몰)을 함유한 아세토니트릴 (170ml)용액을 적가했다. 결과 생긴 혼합물을 환류하에서 20시간 동안 가열하고, 0℃로 냉각하여 1차 산물을 침전시키고, 이것을 여과하여 모았다. 여액을 증발시키고 잔사를 에테르로 연화하여 2차 산물을 얻었다. 이것을 모아 메탄올에 용해하고, 결과가 생긴 용액을 활성탄으로 처리한 후 여과하고, 여액을 감압하에서 증발 건조시켰다. 잔류 기름을 냉각하고, 에테르로 재결정하고, 이어 생성물을 에테르 및 아세토니트릴로 연화한 후, 60℃진공하에서 72시간 동안 건조시켜, 융점 146-147℃인 무색 과립상의 1,12-비스-[4-(2-에틸헥실아미노-1-피리디늄] 도데칸 디브로마이드 14.7g을 얻었다.C. 10.3 g (0.05 mol) of acetonitrile (50 ml) solution of 4- (2-ethylhexylamino) pyridine is warmed and stirred, and then contains 8.2 g (0.025 mol) of 1,12-dibromododecane. One acetonitrile (170 ml) solution was added dropwise. The resulting mixture was heated at reflux for 20 hours, cooled to 0 ° C. to precipitate the primary product which was collected by filtration. The filtrate was evaporated and the residue was triturated with ether to give a secondary product. This was collected, dissolved in methanol, and the resulting solution was treated with activated charcoal, filtered, and the filtrate was evaporated to dryness under reduced pressure. The residual oil is cooled, recrystallized with ether, the product is then softened with ether and acetonitrile and dried under vacuum at 60 ° C. for 72 hours to give a colorless granular 1,12-bis- [4 with melting point of 146-147 ° C. 14.7 g of-(2-ethylhexylamino-1-pyridinium] dodecane dibromide was obtained.

[실시예 42]Example 42

A. 4-(2-(에틸헥실아미노 피리딘 353.5g(1.72몰)과 1,12-디클로로도데칸 205g(0.86몰)와 혼합물을 120℃로 가열한 후 열원을 제거했다. 발열반응에 의해 온도가 180-190℃로 상승하였다. 온도가 135℃로 벌어졌을 때 아세토니트릴 1ℓ를 주의깊게 가하고, 혼합물을 환류하에서 가열하여 맑은 용액을 얻었다. 뜨거운 아세토니트릴 용액을 두개의 다른 류(流)로 부터의 유사한 용액과 합하고, 활성탄으로 처리한 후 여과했다. 여액을 냉각시키고 침전된 생성물을 여과하여 모은 후, 차가운 아세토니트릴로 세척했다. 아세토니트릴로 2번 재결정시켜, 융점 168-171℃인 1,12-비스-[4-(2-에틸헥실아미노)-1-피리디늄]도 데칸 디클로라이드 970g을 얻었다A. The mixture of 4- (2- (ethylhexylamino pyridine 353.5 g (1.72 mol) and 205 g (0.86 mol) 1,12-dichlorododecane was heated to 120 ° C. and the heat source was removed. Rose to 180-190 ° C. When the temperature reached 135 ° C. 1 L of acetonitrile was carefully added and the mixture was heated under reflux to obtain a clear solution A hot acetonitrile solution from two different streams. Combined with a similar solution, treated with activated charcoal and filtered, the filtrate was cooled and the precipitated product was collected by filtration, washed with cold acetonitrile, recrystallized twice with acetonitrile, 1,12 with melting point 168-171 ° C. -Bis- [4- (2-ethylhexylamino) -1-pyridinium] also obtained 970 g of decane dichloride

B. 다른 방법으로서, 1,12-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 도데칸 디브로마이드 3.0g(0.00405몰)을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 172-173℃인 상응하는 디클로라이드 2.0g을 얻었다.B. Similar to Example 2, except that 3.0 g (0.00405 moles) of 1,12-bis- [4- (2-ethylhexylamino) -1-pyridinium] dodecane dibromide was used as another method. The reaction was carried out to give 2.0 g of the corresponding dichloride having a melting point of 172-173 ° C.

[실시예 45]Example 45

4-(옥틸아미노)피리딘 10.3g(0.05몰)과 1,7-디브로모헵탄 6.45g(0.025몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 129-131℃인 1,7-비스-[4-(옥틸아미노)-1-피리디늄] 헵탄 디브로마이드 14.85g을 얻었다.Melting point 129-131 ° C by reaction in a similar manner as in Example 41C, except that 10.3 g (0.05 mol) of 4- (octylamino) pyridine and 6.45 g (0.025 mol) of 1,7-dibromoheptane were used. 14.85 g of phosphorous 1,7-bis- [4- (octylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 44]Example 44

A. 4-(옥틸아미노)피리딘 11.1g(0.054몰)과 1,9-디브로모노난 7.72g(0.027몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 117-119℃인 1,9-비스-[4-(옥틸아미노)-1-피리디늄] 노난 디브로마이드 17.0g을 얻었다.A. Melting point 117- by reacting in a similar manner as in Example 41C, except that 11.1 g (0.054 mol) of 4- (octylamino) pyridine and 7.72 g (0.027 mol) of 1,9-dibromononane were used. 17.0 g of 1,9-bis- [4- (octylamino) -1-pyridinium] nonane dibromide at 119 ° C was obtained.

B. 실시예 2의 방법으로, 융점 161-162℃인 상응하는 디클로라이드를 제조했다.B. By the method of Example 2, the corresponding dichloride was prepared having a melting point of 161-162 ° C.

[실시예 45]Example 45

4-(옥틸아미노)피리딘 10.3g(0.05몰)과 1,12-디브로모데칸 8.2g(0.025몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 119-120℃인 1,12-비스-[4-(옥틸아미노)-1-피리디늄] 도데칸 디브로마이드 15.2g을 얻었다.Melting point 119-120 ° C by reaction in the same manner as in Example 41C, except that 10.3 g (0.05 mol) of 4- (octylamino) pyridine and 8.2 g (0.025 mol) of 1,12-dibromodecane were used. 15.2 g of phosphorus 1,12-bis- [4- (octylamino) -1-pyridinium] dodecane dibromide was obtained.

[실시예 46]Example 46

4-(옥틸아미노)피리딘 5.8g(0.028몰)과 1,14-디브로모테트라데칸 5.0g (0.014몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 113-115℃인 1,14-비스-[4-(옥틸아미노)-1-피리디늄] 테트라데칸 디브로마이드 9.3g을 얻었다.Melting point 113-115 by reaction in a similar manner as in Example 41C, except that 5.8 g (0.028 mol) of 4- (octylamino) pyridine and 5.0 g (0.014 mol) of 1,14-dibromotetradecane were used. 9.3g of 1,14-bis- [4- (octylamino) -1-pyridinium] tetradecane dibromide which is ° C was obtained.

[실시예 47]Example 47

4-(노닐아미노)피리딘 11.0g(0.05몰)과 1,6-디브로모헥산 6.1g(0.025몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 152-154℃인 1,6-비스-[4-(노닐아미노)-1-피리디늄] 헥산 디브로마이드 15.2g을 얻었다.Melting point 152-154 ° C by reaction in a similar manner as in Example 41C, except that 11.0 g (0.05 mol) of 4- (nonylamino) pyridine and 6.1 g (0.025 mol) of 1,6-dibromohexane were used. 15.2 g of phosphorous 1,6-bis- [4- (nonylamino) -1-pyridinium] hexane dibromide was obtained.

[실시예 48]Example 48

1,6-비스-[4-(노닐아미노)-1-피리디늄] 헥산 디브로마이드 6.5g(0.0095몰)을 사용한 것을 제외하고는 실시예 4에서와 유사한 방법으로 반응시켜, 융점 194-195℃인 상응하는 디클로라이드 4.95g을 얻었다.1,6-bis- [4- (nonylamino) -1-pyridinium] Hexane dibromide was reacted in a similar manner as in Example 4 except that 6.5 g (0.0095 mol) was used, and the melting point was 194-195 ° C. 4.95 g of phosphorous dichloride was obtained.

[실시예 49]Example 49

4-(노닐아미노)피리딘 8.8g(0.4몰)과 1,7-디브로모헵탄 5.2g(0.02몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 132-134℃인 1,7-비스-[4-(노닐아미노)-1-피리디늄] 헵탄 디브로마이드 12.2g을 얻었다.Melting point 132-134 ° C by reaction in a similar manner as in Example 41C, except that 8.8 g (0.4 mol) of 4- (nonylamino) pyridine and 5.2 g (0.02 mol) of 1,7-dibromoheptane were used. 12.2 g of phosphorous 1,7-bis- [4- (nonylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 50]Example 50

4-(노닐아미노)피리딘 11.0g(0.05몰)과 1,9-디브로모노난 7.15g(0.025몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 121-122℃인 1,9-비스-[4-(노닐아미노)-1-피리디늄] 노난 디브로마이드 15.7g을 얻었다.Melting point 121-122 ° C by reaction in a similar manner as in Example 41C, except that 11.0 g (0.05 mol) of 4- (nonylamino) pyridine and 7.15 g (0.025 mol) of 1,9-dibromononane were used. 15.7 g of phosphorous 1,9-bis- [4- (nonylamino) -1-pyridinium] nonane dibromide was obtained.

[실시예 51]Example 51

4-(노닐아미노)피리딘 11.0g(0.05몰)과 1,10-디브로모메칸 7.5g(0.025몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 172-173℃인 1,10-비스-[4-(노닐아미노)-1-피리디늄] 데칸 디브로마이드 15.63g을 얻었다.Melting point 172-173 ° C by reaction in a similar manner as in Example 41C, except that 11.0 g (0.05 mol) of 4- (nonylamino) pyridine and 7.5 g (0.025 mol) of 1,10-dibromomecan were used. 15.63 g of phosphorous 1,10-bis- [4- (nonylamino) -1-pyridinium] decane dibromide was obtained.

[실시예 52]Example 52

4-(노닐아미노)피리딘 10.12g(0.046몰)과 1,12-디브로모도데칸 7.54g(0.023몰)을 사용한 것을 제외하고는 실시예 41C에서와 유사한 방법으로 반응시켜, 융점 105-106℃인 1,12-비스-[4-(노닐아미노)-1-피리디늄] 도데칸 디브로마이드 16.4g을 얻었다.Melting point 105-106 ° C by reaction in a similar manner as in Example 41C, except that 10.12 g (0.046 mol) of 4- (nonylamino) pyridine and 7.54 g (0.023 mol) of 1,12-dibromododecane were used 16.4 g of phosphorous 1,12-bis- [4- (nonylamino) -1-pyridinium] dodecane dibromide was obtained.

[실시예 53]Example 53

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)을 함유한 아세토니트릴 (100ml)용액을 교반하고 가온한후, 여기에 1,5-디브로모펜탄 6.9g(0.03몰)의 아세토니트릴 (25ml)용액을 적가하고, 결과 생성된 용액을 환류하에서 20시간 동안 가열했다. 반응 혼합물을 냉각하고, 약간 혼탁해질 때까지 에테르로 희석했다. 다시 냉각하고 교반하여 고형 침전을 얻고, 이것을 여과하여 모은 후 아세토니트릴과 에테르의 차가운 혼합물로 세척했다. 이렇게 얻은 고체를 에탄올에 녹이고, 결과 생긴 용액을 활성탄으로처리하고 여과했다. 여액을 증발시켜, 점성이 있는 엷은 황색의 기름을 얻고 이것을 아세토니트릴-에테르로 결정화시켰다. 결과 생긴 고테를 여과하고 수거하여 차가운 아세토니트릴-에테르로 세척한 후, 90℃ 진공하에서 24시간 건조시켜, 융점 150-151℃인 1,5-비스-[4-(2-에틸헥실아미노)-1-피리디늄]펜탄 디브로마이드 13.6g을 얻었다.After stirring and warming the acetonitrile (100 ml) solution containing 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine, 6.9 g (0.03 mol) of aceto of 1,5-dibromopentane was added thereto. Nitrile (25 ml) solution was added dropwise and the resulting solution was heated at reflux for 20 h. The reaction mixture was cooled and diluted with ether until slightly cloudy. It was cooled again and stirred to give a solid precipitate, which was collected by filtration and washed with a cold mixture of acetonitrile and ether. The solid thus obtained was dissolved in ethanol and the resulting solution was treated with activated carbon and filtered. The filtrate was evaporated to give a viscous pale yellow oil which was crystallized from acetonitrile-ether. The resulting Gote was collected by filtration, washed with cold acetonitrile-ether, and dried under vacuum at 90 ° C. for 24 hours to give 1,5-bis- [4- (2-ethylhexylamino)-with a melting point of 150-151 ° C. 13.6 g of 1-pyridinium] pentane dibromide was obtained.

[실시예 54]Example 54

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)과 1,6-디브로모헥산 7.32g(0.03몰)을 사용한 것을 제외하고는 실시예 53에서와 유사한 방법으로 반응시켜, 융점 208-209℃인 1,6-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 헥산 디브로마이드 16.1g을 얻었다.Melting point 208 was carried out in the same manner as in Example 53, except that 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine and 7.32 g (0.03 mol) of 1,6-dibromohexane were used. 16.1 g of 1,6-bis- [4- (2-ethylhexylamino) -1-pyridinium] hexane dibromide at -209 ° C was obtained.

[실시예 55]Example 55

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)과 1,7-디브로모헵탄 7.75g(0.03몰)을 사용한 것을 제외하고는 실시예 53에서와 유사한 방법으로 반응시켜, 융점 219-220℃인 1,7-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 헵탄 디브로마이드 17.9g을 얻었다.Melting point 219 by reaction in a similar manner as in Example 53, except that 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine and 7.75 g (0.03 mol) of 1,7-dibromoheptane were used. 17.9 g of 1,7-bis- [4- (2-ethylhexylamino) -1-pyridinium] heptane dibromide at -220 ° C was obtained.

[실시예 56]Example 56

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)과 1,8-디브로모옥탄 8.2g(0.03몰)을 사용한 것을 제외하고는 실시예 53에서와 유사한 방법으로 반응시켜, 융점 160-161℃인 1,8-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 옥탄 디브로마이드 15.2g을 얻었다.Melting point 160 by reaction in a similar manner as in Example 53, except that 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine and 8.2 g (0.03 mol) of 1,8-dibromooctane were used. 15.2g of 1,8-bis- [4- (2-ethylhexylamino) -1-pyridinium] octane dibromide which is -161 degreeC was obtained.

[실시예 57]Example 57

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)과 1,9-디브로모노난 8.6g(0.03몰)을 사용한 것을 제외하고는 실시예 53에서와 유사한 방법으로 반응시켜, 융점 158-159℃인 1,9-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 노난 디브로마이드 15.2g을 얻었다.Melting point 158 by reaction in a similar manner as in Example 53, except that 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine and 8.6 g (0.03 mol) of 1,9-dibromononane were used. 15.2 g of 1,9-bis- [4- (2-ethylhexylamino) -1-pyridinium] nonane dibromide at -159 ° C was obtained.

[실시예 58]Example 58

4-(2-에틸헥실아미노)피리딘 12.4g(0.06몰)과 1,10-디브로모데칸 9.0g(0.03몰)을 사용한 것을 제외하고는 실시예 53에서와 유사한 방법으로 반응시켜, 융점 162-163℃인 1,10-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 데칸 디브로마이드 17.4g을 얻었다.Melting point 162 was carried out in a similar manner as in Example 53, except that 12.4 g (0.06 mol) of 4- (2-ethylhexylamino) pyridine and 9.0 g (0.03 mol) of 1,10-dibromodecane were used. 17.4 g of 1,10-bis- [4- (2-ethylhexylamino) -1-pyridinium] decane dibromide at -163 ° C was obtained.

[실시예 59]Example 59

1-10-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 데칸 디브로마이드 5.0g을 사용한 것을 제외하고는 실시예 2에서와 유사한 방법으로 반응시켜, 융점 191-192℃인 상응하는 디클로라이드 4.11g을 얻었다.The reaction was carried out in the same manner as in Example 2 except that 5.0 g of 1-10-bis- [4- (2-ethylhexylamino) -1-pyridinium] decane dibromide was used, and the melting point was 191-192 ° C. 4.11 g of the corresponding dichloride was obtained.

[실시예 60]Example 60

4-(헵틸아미노)피리딘 12.0g(0.063몰)의 아세토니트릴 (100ml 용액을 교반하고 가온한 후, 여기에 1,5-디브로모펜탄 7.1g(0.032몰)의 아세토니트릴 (25ml)용액을 적가하고, 결과 생신 혼합물을 환류하에서 19시간 동안 가열했다. 반응 혼합물을 얼음에 냉각하고, 무색의 고체가 침전될 대까지 에테르를 서서히 가했다. 고체를 여과하여 모으고, 아세토니트릴-에테르로 재결정시킨 후 90℃/1mm에서 48시간 건조시켜, 융점 153-154℃인 1.5-비스-[4-(헵틸아미노)-1-피리디늄] 펜탄 디브로마이드 15.9g을 얻었다.After stirring and warming 12.0 g (0.063 mol) of acetonitrile (100 ml solution of 4- (heptylamino) pyridine (100 ml solution), 7.1 g (0.032 mol) of acetonitrile (25 ml) solution of 1,5-dibromopentane was added thereto. The reaction mixture was heated to reflux for 19 hours under reflux, and the reaction mixture was cooled on ice and ether slowly added until a colorless solid precipitated out, the solids were collected by filtration and recrystallized from acetonitrile-ether. It dried for 48 hours at 90 degreeC / 1mm, and obtained 15.9g of 1.5-bis- [4- (heptylamino) -1-pyridinium] pentane dibromide which has a melting point of 153-154 degreeC.

[실시예 61]Example 61

4-(헵틸아미노)피리딘 19.2g(0.1몰)의 1,6-디브로모헥산 12.2g(0.05몰)을 사용한 것을 제외하고는 실시예 60에서와 유사한 방법으로 반응시켜, 조잡한 생성물 27.5g을 얻었다. 샘플 15g을 아세토니트릴-에테르로 재결정시켜, 융점 149-150℃인 1,6-비스-[4-(헵틸아미노)-1-피리디늄] 헥산 비드로마이드 11.45g을 얻었다.27.5 g of crude product was reacted in a similar manner as in Example 60 except that 12.2 g (0.05 mole) of 1,6-dibromohexane of 19.2 g (0.1 mole) of 4- (heptylamino) pyridine was used. Got it. 15 g of the sample was recrystallized from acetonitrile-ether to obtain 11.45 g of 1,6-bis- [4- (heptylamino) -1-pyridinium] hexane beadamide having a melting point of 149-150 ° C.

[실시예 62]Example 62

조잡한 1,6-비스-[4-(헵틸아미노)-1-피리디늄] 헥산 디브로마이드 24.0g을 물 500ml에 가한 현탁액을 3N 수산화바트륨 수용액으로 알칼리성화 한 후, 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황산나트륨 상에서 건조시킨 후 감압하에서 증발 건조시켰다. 잔류 기름을 메탄올에 용해시켜 얻은 용액을 메탄-설폰산으로 산성화한 후, 감압하에서 증발 건조시켰다. 잔사를 메탄올에 재용해시키고, 활성탄으로 처리한 후 여과하고, 감압하에서 증발 건조시켜, 기름상 잔사를 얻고, 에테르 및 아세트니트릴로 연화하여 고무질 고체 18.2g을 얻었다. 이때 얻은 조잡한 교체를 물에 용해시켜 얻은 용액을 35% 수산화나트륨 수용액으로 알칼리성으로 만들고 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황산나트륨상에서 건조시킨 후 감압하에서 증발 건조시켰다. 결과 생긴 고체를 에테르 및 아세토니트릴로 연화하고, 여과하여 모은 후 건조시켜, 융점 105-108℃의 황갈색 고체 16.3g을 얻었다. 이렇게 얻은 고체를 메탄올 100ml에 용해시켜 얻은 용액을 메탄설폰산으로 산성화했다. 감압하에서 증발 건조시켜 점성이 있는 기름을 얻고, 이것을 메탄올 20ml에 용해한 후 물 150ml로 조금씩 처리했다. 결과 생긴 현탁액을 얼음에 냉각시키고, 부유 고체를 여과하여 모은 후 냉수로 세척했다. 고체를 뜨거운 아세톤에 슬러리화하고 냉각 시킨 후 여과하여 모으고, 차가운 아세톤으로 세척한 후, 95℃/1mm에서 48시간 건조시켜, 융점 163-165℃인 황갈색 고체 10.8g을 얻었다. 이 생성물은 질산은에 의한 염소 이온 검사에서 양성이었으며, 헥자기 공명스펙트럼에서 메탄설포네이트기가 나타나지 않았다.A suspension obtained by adding 24.0 g of crude 1,6-bis- [4- (heptylamino) -1-pyridinium] hexane dibromide to 500 ml of water was alkalized with an aqueous 3N barium hydroxide solution, and then extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and then evaporated to dryness under reduced pressure. The solution obtained by dissolving the residual oil in methanol was acidified with methane-sulfonic acid and then evaporated to dryness under reduced pressure. The residue was redissolved in methanol, treated with activated charcoal, filtered and evaporated to dryness under reduced pressure to give an oily residue which was triturated with ether and acetonitrile to give 18.2 g of a gummy solid. The crude replacement obtained was dissolved in water and the solution obtained was made alkaline with 35% aqueous sodium hydroxide solution and extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and then evaporated to dryness under reduced pressure. The resulting solid was triturated with ether and acetonitrile, collected by filtration and dried to give 16.3 g of a tan solid with a melting point of 105-108 ° C. The solution obtained was dissolved in 100 ml of methanol and the resulting solution was acidified with methanesulfonic acid. Evaporated to dryness under reduced pressure to give a viscous oil, which was dissolved in 20 ml of methanol and treated with 150 ml of water little by little. The resulting suspension was cooled on ice and the suspended solids were collected by filtration and washed with cold water. The solid was slurried in hot acetone, cooled, collected by filtration, washed with cold acetone, and dried for 48 hours at 95 ° C./1 mm to give 10.8 g of a tan solid having a melting point of 163-165 ° C. This product was positive in the chlorine ion test by silver nitrate, and no methanesulfonate group appeared in the hex resonance spectrum.

B. 1,6-비스-[4-(헵틸아미노)-1-피리디늄] 헥산 디브로마이드 14.0g을 물 500ml에 가한 현탁액을 35% 수산화나트륨 수용액으로 알칼리성으로 한 후, 클로로포름으로 추출했다. 클로로포름 추출물을 무수 황산 나트륨상에서 건조시키고, 감압하에서 증발 건조시켰다. 부분적으로 고형인 잔사를 아세토니트릴-벤젠 1ℓ에 녹여 얻은 용액을 진공하에서 증발 건조시켰다. 이 과정을 3번 반복했다. 최종 잔사를 아세토니트릴 50ml에 용해시키고 결과 생긴 용액을 벤젠 50ml로 희석한 후 얼음에 냉각하고, 여과하고 건조시켜 황갈색 고체 5.3g을 얻었다. 여액으로 부터 2차 산물 4.8g을 얻었다. 이것을 합해 아세토니트릴 50ml에 용해 시켰다. 침전된 고체를 에테르로 희석하고, 여과하여 모은 후 95℃/1mm에서 48시간 건조시켜, 융점 174-176℃인 황갈색 고체 8.85g을 얻었다. 이 생성물도 역시 질산온에 의한 염소 이온 검사에서 양성을 나타냈다.B. 1,6-bis- [4- (heptylamino) -1-pyridinium] 14.0 g of hexanes dibromide was added to 500 ml of water, and the suspension was made alkaline with 35% aqueous sodium hydroxide solution and then extracted with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The solution obtained by dissolving the partially solid residue in 1 L of acetonitrile-benzene was evaporated to dryness in vacuo. This process was repeated three times. The final residue was dissolved in 50 ml of acetonitrile and the resulting solution was diluted with 50 ml of benzene, cooled on ice, filtered and dried to give 5.3 g of a tan solid. From the filtrate, 4.8 g of secondary product was obtained. This was combined and dissolved in 50 ml of acetonitrile. The precipitated solid was diluted with ether, collected by filtration and dried for 48 hours at 95 ° C / 1 mm to obtain 8.85 g of a tan solid having a melting point of 174-176 ° C. This product was also positive in the chlorine ion test by nitric acid temperature.

C. 상기 A와 B의 생성물을 합하여 물 300ml와 혼합하고, 균질한 용액이 될때까지 가열했다. 용액을 여과하고, 여액을 12N 염산 50ml로 처리했다. 결과 생긴 현탁액을 감압하에서 농축하고, 잔사를 얼음으로 처리했다. 이렇게 얻은 고체를 여과하여 수거하고, 냉수로 세척한 후 건조시켰다. 이 생성물을 아세톤에 녹이고, 결과 생긴 용액을 벤젠과 에탄올의 혼합물로 희석한 후, 진공하에서 모두 증발 건조시켰다. 고형 잔사를 아세톤 100ml에 슬러리화 하고, 그 슬러리를 에테르로 희석하고 여과한 후, 105℃/1mm에서 48시간, 115℃/1mm에서 72시간 동안 건조시켜, 융점 176-178℃인 회백색 고체상의 조잡한 1,6-비스-[4-(헵틸아미노)-1-피리디늄]헥산 디클로라이드 16.3g을 얻었다.C. The products of A and B were combined and mixed with 300 ml of water and heated until a homogeneous solution. The solution was filtered and the filtrate was treated with 50 ml of 12N hydrochloric acid. The resulting suspension was concentrated under reduced pressure and the residue was treated with ice. The solid thus obtained was collected by filtration, washed with cold water and dried. This product was dissolved in acetone and the resulting solution was diluted with a mixture of benzene and ethanol and then all evaporated to dryness in vacuo. The solid residue was slurried in 100 ml of acetone, the slurry was diluted with ether, filtered and dried for 48 hours at 105 ° C./1 mm and 72 hours at 115 ° C./1 mm to give a coarse white solid at a melting point of 176-178 ° C. 16.3 g of 1,6-bis- [4- (heptylamino) -1-pyridinium] hexane dichloride was obtained.

[실시예 63]Example 63

4-(2-에틸헥실아미노)피리딘 10.30g(0.050몰)과 1,4-디브로모부탄 5.4g(0.025몰)을 사용한 것을 제외하고는 실시예 60에서와 유사한 방법으로 반응시켜, 융점 245-246℃인 1,4-비스-[4-(2-에틸헥실아미노)-1-피리디늄] 헥산 디브로마이드 14.0g을 얻었다.Melting point 245 was carried out in the same manner as in Example 60, except that 10.30 g (0.050 mol) of 4- (2-ethylhexylamino) pyridine and 5.4 g (0.025 mol) of 1,4-dibromobutane were used. 14.0 g of 1,4-bis- [4- (2-ethylhexylamino) -1-pyridinium] hexane dibromide at -246 ° C was obtained.

[실시예 64]Example 64

A. N-(4-피리딘)피리디늄 클로라이드 하이드로클로라이드 229g(1.0몰)과 n-데실아민 하이드로클로라이드 244g(1.26몰)의 혼합물을 교반한 후, 190-195℃에서 약 2.5시간 가열했다. 반응 혼합물을 서서히 40℃로 냉각한 후 물 2ℓ로 희석했다. 결과 생긴 용액에 얼음을 가하여 냉각한 후, 35% 수산화나트륨 수용액 200ml로 알칼리성으로 했다. 분리된 거무스름한 고체를 여과하여 모으고, 냉수로 세척했다. 이 물질을 클로로포름 1ℓ에 용해시킨 후, 얻은 용액을 활성탄으로 세척하고 여과했다. 여액을 감압하에서 증발 시키고, 잔사를 에테르 150ml로 연화했다. 이렇게 얻은 고체를 클로로포름에 재용해시켜 얻은 용액을 활성탄으로 처리한 후 여과했다. 여액을 활성탄으로 다시 처리한 후 여과했다. 여액을 감압하에서 증발 건조시키고, 잔류 고체를 에테르로 연화했다. 아세토니트릴로 재결정시키고 진공 건조시켜, 융점 71-73℃인 4-(데실아미노)피리딘 96.1g을 얻었다.A. A mixture of 229 g (1.0 mole) of N- (4-pyridine) pyridinium chloride hydrochloride and 244 g (1.26 mole) of n-decylamine hydrochloride was stirred and then heated at 190-195 ° C. for about 2.5 hours. The reaction mixture was slowly cooled to 40 ° C. and diluted with 2 liters of water. Ice was added to the resultant solution, followed by cooling, and made alkaline with 200 ml of 35% aqueous sodium hydroxide solution. The separated blackish solid was collected by filtration and washed with cold water. After dissolving this material in 1 l of chloroform, the resulting solution was washed with activated charcoal and filtered. The filtrate was evaporated under reduced pressure and the residue was triturated with 150 ml of ether. The solution obtained by dissolving the solid thus obtained in chloroform was treated with activated carbon and filtered. The filtrate was again treated with activated charcoal and filtered. The filtrate was evaporated to dryness under reduced pressure and the residual solid was triturated with ether. Recrystallized from acetonitrile and dried in vacuo to give 96.1 g of 4- (decylamino) pyridine having a melting point of 71-73 占 폚.

B. 4-(데실아미노)피리딘 12.2g(0.052몰)- 아세토니트릴(150-170ml) 용액을 교반하고 가온한 후, 여기에 1,6-디브로모헥산 6.35(0.026몰)을 함유한 아세토니트릴(60ml)용액을 적가했다. 결과 생긴 혼합물을 환류하에서 약 20시간동안 가열했다. 반응 혼합물을 얼음으로 냉각하고, 침전된 고체를 여과하여 수거한 후, 차가운 아세토니트릴로 세척했다 이렇게 얻은 생성물을 메탄올에 용해시키고, 결과 생긴 용액을 활성탄으로 처리한 후 여과했다. 여액을 감압하에서 증발 건조시키고, 원사를 차가운 에테르 50ml로 연화하고 여과하여 모은 후, 70℃/0.1mm 오산화인 상에서 2일간 건조시켜, 융점 138-140℃의 1,6-비스-[4-(데실아미노)-1-피리디늄] 헥산 디브로마이드 14.6g을 얻었다.B. 12.2 g (0.052 mol) of a 4- (decylamino) pyridine-acetonitrile (150-170 ml) solution was stirred and warmed, followed by aceto containing 6.35 (0.026 mol) of 1,6-dibromohexane. Nitrile (60 ml) solution was added dropwise. The resulting mixture was heated at reflux for about 20 hours. The reaction mixture was cooled with ice and the precipitated solid was collected by filtration and washed with cold acetonitrile. The product thus obtained was dissolved in methanol and the resulting solution was treated with activated charcoal and filtered. The filtrate was evaporated to dryness under reduced pressure, the yarn was triturated with 50 ml of cold ether, collected by filtration, and dried over 70 days at 70 ° C./0.1 mm phosphorus pentoxide to give 1,6-bis- [4- ( Decylamino) -1-pyridinium] hexane dibromide 14.6 g was obtained.

[실시예 65]Example 65

4-(데실아미노)피리딘 12.2g(0.052몰)과 1,7-디브로모헵탄 6.7g(0.026몰)을 사용한 것을 제외하고는 실시예 64B에서와 유사한 방법으로 반응시켜, 융점 145-147℃인 1,8-비스-[4-(데실아미노)-1-피리디늄] 헵탄 디브로마이드 16.0g을 얻었다.Melting point 145-147 ° C by reaction in a similar manner as in Example 64B, except that 12.2 g (0.052 mol) of 4- (decylamino) pyridine and 6.7 g (0.026 mol) of 1,7-dibromoheptane were used. 16.0 g of phosphorous 1,8-bis- [4- (decylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 66]Example 66

4-(데실아미노)피리딘 11.7g(0.050몰)과 1,8-디브로모옥탄 6.8g(0.025몰)을 사용한 것을 제외하고는 실시예 64B에서와 유사한 방법으로 반응시켜, 융점 180-182℃인 1,8-비스-[4-(데실아미노)-1-피리디늄] 옥탄 디브로마이드 16.9g을 얻었다.Melting point 180-182 ° C by reaction in a similar manner as in Example 64B, except that 11.7 g (0.050 mole) of 4- (decylamino) pyridine and 6.8 g (0.025 mole) of 1,8-dibromooctane were used. 16.9 g of phosphorous 1,8-bis- [4- (decylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 67]Example 67

4-(데실아미노)피리딘 11.7g(0.050몰)과 1,9-디브로모노난 7.15g(0.025몰)을 사용한 것을 제외하고는 실시예 64B에서와 유사한 방법으로 반응시켜, 융점 124-126℃인 1,9-비스-[4-(데실아미노)-1-피리디늄] 노난 디브로마이드 15.1g을 얻었다.Melting point 124-126 ° C by reaction in a similar manner as in Example 64B, except that 11.7 g (0.050 mole) of 4- (decylamino) pyridine and 7.15 g (0.025 mole) of 1,9-dibromononane were used. 15.1 g of phosphorous 1,9-bis- [4- (decylamino) -1-pyridinium] nonane dibromide was obtained.

[실시예 68]Example 68

4-(데실아미노)피리딘 11.2g(0.048몰)과 1,10-디브로모옥탄 7.2g(0.024몰)을 사용한 것을 제외하고는 실시예 64B에서와 유사한 방법으로 반응시켜, 융점 173-174℃인 1,10-비스-[4-(데실아미노)-1-피리디늄] 옥탄 디브로마이드 14.6g을 얻었다.Melting point 173-174 ° C. by reaction in a similar manner as in Example 64B, except that 11.2 g (0.048 mole) of 4- (decylamino) pyridine and 7.2 g (0.024 mole) of 1,10-dibromooctane were used. 14.6 g of phosphorous 1,10-bis- [4- (decylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 69]Example 69

4-(데실아미노)피리딘 11.2g(0.050몰)과 1,12-디브로모도데칸 7.9g(0.024몰)을 사용한 것을 제외하고는 실시예 64B에서와 유사한 방법으로 반응시켜, 융점 102-106℃인 1,12-비스-[4-(데실아미노)-1-피리디늄] 도데칸 디브로마이드 16.5g을 얻었다.Melting point 102-106 ° C by reaction in a similar manner as in Example 64B, except that 11.2 g (0.050 mole) of 4- (decylamino) pyridine and 7.9 g (0.024 mole) of 1,12-dibromododecane were used. 16.5 g of phosphorus 1,12-bis- [4- (decylamino) -1-pyridinium] dodecane dibromide was obtained.

[실시예 70]Example 70

4-(도데실아미노)피리딘 13.6g(0.052몰)을 함유한 아세트니트릴 (140ml)용액을 교반하고 가온한 후, 1,6-디브로모헥산 6.34g(0.026몰)의 아세토니트릴 (50ml)용액을 적가하고, 결과 생긴 혼합물을 환류하에서 밤새 가열했다. 반응 혼합물을 냉각하고, 침전된 고체를 여과하여 모았다. 이 고체를 무수 에탄올에 용해시키고, 결과 생긴 용액을 활성탄으로 처리한 후 여과했다. 여액을 감압하에서 증발 건조시켜서 흰색의 잔류 고체를 얻고 이것을 에테르로 슬러리화하고 여과하여 모은 후 60℃/0.1mm에서 건조시켜, 융점 164-165℃인 1,6-비스-[4-(도데실아미노)-1-피리디늄] 헥산 디브로마이드 17.63g을 얻었다.Acetonitrile (140 ml) solution containing 13.6 g (0.052 mol) of 4- (dodecylamino) pyridine was stirred and warmed, followed by 6.34 g (0.026 mol) of acetonitrile (50 ml) of 1,6-dibromohexane. The solution was added dropwise and the resulting mixture was heated at reflux overnight. The reaction mixture was cooled down and the precipitated solid was collected by filtration. This solid was dissolved in anhydrous ethanol, and the resulting solution was treated with activated carbon and filtered. The filtrate was evaporated to dryness under reduced pressure to give a white residual solid which was slurried with ether, filtered and collected and dried at 60 ° C./0.1 mm to give 1,6-bis- [4- (dodecyl having a melting point of 164-165 ° C. Amino) -1-pyridinium] hexane dibromide 17.63 g was obtained.

[실시예 71]Example 71

4-(도데실아미노)피리딘 13.6g(0.052몰)과 1,7-디브로모헵탄 6.71g(0.026몰)을 사용한 것을 제외하고는 실시예 70에서와 유사한 방법으로 반응시켜, 융점 148-150℃인 1,7-비스-[4-(도데실아미노)-1-피리디늄] 헵탄 디브로마이드 18.03g을 얻었다.Melting point 148-150 by reaction in the same manner as in Example 70 except that 13.6 g (0.052 mol) of 4- (dodecylamino) pyridine and 6.71 g (0.026 mol) of 1,7-dibromoheptane were used. 18.03 g of 1,7-bis- [4- (dodecylamino) -1-pyridinium] heptane dibromide was obtained.

[실시예 72]Example 72

4-(도데실아미노)피리딘 12.59g(0.048몰)과 1,8-디브로모옥탄 6.53g(0.024몰)을 사용한 것을 제외하고는 실시예 70에서와 유사한 방법으로 반응시켜, 융점 148-185℃인 1,8-비스-[4-(도데실아미노)-1-피리디늄] 옥탄 디브로마이드 16.18g을 얻었다.Melting point 148-185 by reaction in a similar manner as in Example 70, except that 12.59 g (0.048 mol) of 4- (dodecylamino) pyridine and 6.53 g (0.024 mol) of 1,8-dibromooctane were used. 16.18 g of 1,8-bis- [4- (dodecylamino) -1-pyridinium] octane dibromide was obtained.

[실시예 73]Example 73

4-(도데실아미노)피리딘 12.59g(0.048몰)과 1,9-디브로모노난 6.86g(0.024몰)을 사용한 것을 제외하고는 실시예 70에서와 유사한 방법으로 반응시켜, 융점 134-135℃인 1,9-비스-[4-(도데실아미노)-1-피리디늄] 노난 디브로마이드 19.35g을 얻었다.Melting point 134-135 by reaction in a similar manner as in Example 70, except that 12.59 g (0.048 mol) of 4- (dodecylamino) pyridine and 6.86 g (0.024 mol) of 1,9-dibromononane were used. 19.35 g of 1,9-bis- [4- (dodecylamino) -1-pyridinium] nonane dibromide was obtained.

[실시예 74]Example 74

4-(도데실아미노)피리딘 12.59g(0.048몰)과 1,10-디브로모데칸 7.2g(0.024몰)을 사용한 것을 제외하고는 실시예 70에서와 유사한 방법으로 반응시켜, 융점 178-180℃인 1,10-비스-[4-(도데실아미노)-1-피리디늄] 데칸 디브로마이드 18.08g을 얻었다.Melting point 178-180 by reaction in a similar manner as in Example 70, except that 12.59 g (0.048 mol) of 4- (dodecylamino) pyridine and 7.2 g (0.024 mol) of 1,10-dibromodecane were used. 18.08 g of 1,10-bis- [4- (dodecylamino) -1-pyridinium] decane dibromide which is ° C was obtained.

[실시예 75]Example 75

4-(도데실아미노)피리딘 11.54g(0.044몰)과 1,12-디브로모데칸 7.22g(0.022몰)을 사용한 것을 제외하고는 실시예 70에서와 유사한 방법으로 반응시켜, 융점 75-77℃인 1,12-비스-[4-(도데실아미노)-1-피리디늄] 도데칸 디브로마이드 17.68g을 얻었다.Melting point 75-77 by reacting in a similar manner as in Example 70, except that 11.54 g (0.044 mol) of 4- (dodecylamino) pyridine and 7.22 g (0.022 mol) of 1,12-dibromodecane were used. 17.68 g of 1,12-bis- [4- (dodecylamino) -1-pyridinium] dodecane dibromide was obtained.

[실시예 76]Example 76

A. 4-(P-클로로페닐아미노)피리딘 21.0g(0.102몰)을 함유한 N,N-디메틸포름아미드 (150ml)용액을 교반하여 가온한 후, 1,4-디브로모부탄 11.02g(0.051몰)을 함유한 아세토니트릴 (50ml)용액을 적가했다. 결과 생긴 혼합물을 증기욕에서 2.5시간 동안 가열했다. 반응 혼합물을 실온에서 냉각하고, 에테르로 휘석하고 생성물을 결정화시켰다. 침전된 고체를 여과하여 모으고, 아세토니트릴과 에테르의 혼합물로 세척한 후 공기중에서 건조시켜, 융점 182-189℃인 1,4-비스-[4-(P-클로로페닐아미노)-1-피리디듐] 부탄 디브로마이드 27.4g을 얻었다.A. A solution of N, N-dimethylformamide (150 ml) containing 21.0 g (0.102 mol) of 4- (P-chlorophenylamino) pyridine was stirred and warmed, followed by 11.02 g of 1,4-dibromobutane. Acetonitrile (50 ml) solution containing 0.051 mol) was added dropwise. The resulting mixture was heated in a steam bath for 2.5 hours. The reaction mixture was cooled at room temperature, bevoled with ether and the product crystallized. The precipitated solids were collected by filtration, washed with a mixture of acetonitrile and ether, and then dried in air to produce 1,4-bis- [4- (P-chlorophenylamino) -1-pyridium with a melting point of 182-189 ° C. 27.4 g of butane dibromide were obtained.

B. 상기 생성물은 물 500ml에 현탁시킨 현탁액을 얼음 및 2N 수산화나트륨 수용액으로 처리했다. 결과 생긴 혼합물을 클로로포름으로 완전 추출했다. 클로로포름 추출물을 무수 황산나트륨 상에서 건조하고 감압하에서 증발 건조 시킴으로써, 정치하면 고체화되는 기름상태의 상용하는 무수염기 21.0g을 얻었다.B. The product was treated with ice and 2N aqueous sodium hydroxide solution in suspension suspended in 500 ml of water. The resulting mixture was extracted completely with chloroform. The chloroform extract was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure to give 21.0 g of a compatible anhydrous base in an oily state which solidified upon standing.

C. 상기 무수 염기를 함유한 메탄올 용액 250ml를 메탄-설폰산의 메탈을 용액으로 산성화 시켰다. 감압하에서 증발 건조시켜서 기름을 얻고, 이것을 메탄올-에테르로 결정화켰다. 이렇게 얻은 고체를 메탄올-에테르로 재결정시키고 92℃/0.1mm에서 48시간 동안 건조시켜, 융점 245-247℃인 1,4-비스[4-(P-클로로 페닐아미노(-1-피리디늄]부탄 디메틸설포 네이트 18.95를 얻었다C. 250 ml of the methanol solution containing the anhydrous base was acidified with a metal of methane-sulfonic acid. Evaporation to dryness under reduced pressure afforded an oil which was crystallized from methanol-ether. The solid thus obtained was recrystallized from methanol-ether and dried at 92 ° C./0.1 mm for 48 hours to give 1,4-bis [4- (P-chloro phenylamino (-1-pyridinium] butane having a melting point of 245-247 ° C. Dimethylsulfonate 18.95 was obtained

[실시예 77]Example 77

A. 4-(P-클로로페닐아미노)피리딘 21.0g(0.102몰)을 함유한 N,N-디메틸포름아미드 용액(200ml)을 교반하고 가온한 후, 1,6-디브로모헥산 12.45g(0.051몰)의 아세토니트릴(50ml)용액을 적가하고. 결과 생긴 혼합물을 증기욕에서 4시간 동안 가열했다. 실온으로 냉각하니 고체가 침전하기 시작했다. 반응 혼합물을 아세토니트릴 150ml로 희석하고 얼음에서 한번 더 냉각시켰다. 침전된 고체를 여과하여 모으고 공기 건조시, 켜용 148-150℃점인 1,6-비스-[4-(P-클로로페닐아미노)-1-피리디듐]헥산 디브로마이드 27.2g을 얻었다.A. N, N-dimethylformamide solution (200 ml) containing 21.0 g (0.102 mol) of 4- (P-chlorophenylamino) pyridine was stirred and warmed, followed by 12.45 g of 1,6-dibromohexane. 0.051 mole) of acetonitrile (50 ml) was added dropwise. The resulting mixture was heated in a steam bath for 4 hours. After cooling to room temperature solids began to precipitate. The reaction mixture was diluted with 150 ml of acetonitrile and cooled once more on ice. The precipitated solid was collected by filtration and, upon air drying, 27.2 g of 1,6-bis- [4- (P-chlorophenylamino) -1-pyridinium] hexane dibromide was obtained at a 148-150 ° C. point.

B. 실시예 76B의 방법에 따라 상기 디브로마이드로 부터 제조된 상응하는 무수염기의 메탄올 용액을 메탄설폰산으로 산성화하고, 이어 감압하에서 증발 건조시켰다. 잔류 기름을 아세톤-메탄올로 결정화시키고 75℃/0.1mm에서 48시간 건조시켜, 융점 108-110℃인 1,6-비스-[4-(P-클로로페닐아미노-1-피리디늄]헥산 디메탄설포 네이트 25.2g을 얻었다.B. The methanol solution of the corresponding anhydrous base prepared from the dibromide according to the method of Example 76B was acidified with methanesulfonic acid and then evaporated to dryness under reduced pressure. The residual oil was crystallized with acetone-methanol and dried at 75 ° C./0.1 mm for 48 hours to give 1,6-bis- [4- (P-chlorophenylamino-1-pyridinium] hexane dimethane having a melting point of 108-110 ° C. 25.2 g of sulfonate were obtained.

[실시예 78]Example 78

A. 4-(P-클로로페닐아미노) 피리딘 21.0g(0.102몰)을 함유한 N,N-디메틸포름아미드 용액(200ml)을 교반하고 가온한 후, 1,8-디브로모옥탄 13.9g(0.051몰)을 함유한 아세토니트릴(50ml)용액을 적가하고. 결과 생긴 혼합물을 증기욕에서 1.5시간 동안 가열했다. 반응 혼합물을 아세토니트릴 100ml로 희석하고 2.5시간 동안 더욱 가열한 후 아세토니트릴 100ml를 더욱 가했다. 2시간 더 가열한 후 반응혼합물을 냉각하고, 침전된 고체를 여과하여 모으고 아세토니트릴과 에테르의 혼합물로 세척한 후 건조시켜, 융점 245-247℃인 1,8-비스-[4-(P-클로로 페닐아미노)-1-피리디듐]옥탄 디브로마이드 30.1g을 얻었다.A. N, N-dimethylformamide solution (200 ml) containing 21.0 g (0.102 mol) of 4- (P-chlorophenylamino) pyridine was stirred and warmed, followed by 13.9 g of 1,8-dibromooctane. Acetonitrile (50 ml) solution containing 0.051 mol) was added dropwise. The resulting mixture was heated in a steam bath for 1.5 hours. The reaction mixture was diluted with 100 ml of acetonitrile and further heated for 2.5 hours before further 100 ml of acetonitrile. After further heating for 2 hours, the reaction mixture was cooled, the precipitated solid was collected by filtration, washed with a mixture of acetonitrile and ether, and then dried to obtain 1,8-bis- [4- (P-) having a melting point of 245-247 ° C. 30.1 g of chloro phenylamino) -1-pyrididium] octane dibromide were obtained.

B. 실시예 76B의 방법에 따라 상기 디브로마이드로 부터 제조된 상응하는 무기염기의 메탄올 용액을 메탄설폰산으로 산성화하고, 이어 감압하에서 증발 건조시켰다. 잔류 기름을 아세토니트릴에 녹이고, 결과 생긴 용액을 혼탁해질 때까지 아세톤으로 처리하고 소량의 메탄올로 맑게한 후 냉각시켰다. 침전된 조잡한 고체를 모으고, 아세토니트릴-아세톤으로 재결정화하고 80℃/0.1mm에서 36시간 건조시켜, 융점 164-165℃의 1,8-비스-[4-(P-클로로페닐아미노-1-피리디늄]옥탄 디메탄설포네이트 25.2g을 얻었다.B. The methanol solution of the corresponding inorganic base prepared from the dibromide according to the method of Example 76B was acidified with methanesulfonic acid and then evaporated to dryness under reduced pressure. The residual oil was dissolved in acetonitrile and the resulting solution was treated with acetone until cloudy and cleared with a small amount of methanol and then cooled. The precipitated crude solid was collected, recrystallized from acetonitrile-acetone and dried for 36 hours at 80 ° C./0.1 mm to give 1,8-bis- [4- (P-chlorophenylamino-1- at 164-165 ° C. 25.2 g of pyridinium] octane dimethanesulfonate was obtained.

[실시예 79]Example 79

A. 4-(P-클로로페닐아미노)피리딘 21.0g(0.102몰)을 함유한 N,N-디메틸포름아미드 용액(200ml)을 교반하고 가온한 후, 1,10-디브로모데칸 15.3g(0.0051몰)의 아세토니트릴(50ml)용액을 적가하고. 결과 생긴 혼합물을 증기욕에서 3.5시간 동안 가열했다. 반응 혼합물을 감압하에서 증발 건조시키고, 잔류 기름을 메탄올-아세토니트릴로 결정화 시켰다. 이렇게 생긴 고체를 여과하여 모으고 아세토니트릴과 에테르의 차가운 혼합물로 세척하여, 융점 225-230℃인 1,10-비스-[4-(P-클로로 페닐아미노)-1-피리디듐]데칸 디브로마이드 28.0g을 얻었다.A. N, N-dimethylformamide solution (200 ml) containing 21.0 g (0.102 mol) of 4- (P-chlorophenylamino) pyridine was stirred and warmed, followed by 15.3 g of 1,10-dibromodecane ( 0.0051 mole) of acetonitrile (50 ml) was added dropwise. The resulting mixture was heated in a steam bath for 3.5 hours. The reaction mixture was evaporated to dryness under reduced pressure and the residual oil was crystallized from methanol-acetonitrile. The resulting solids were collected by filtration and washed with a cold mixture of acetonitrile and ether to give 1,10-bis- [4- (P-chloro phenylamino) -1-pyridinium] decane dibromide 28.0 having a melting point of 225-230 ° C. g was obtained.

B. 실시예 76B의 방법에 따라 상기 디브로마이드로 부터 제조된 상응하는 무수염기의 메탄올 용액을 메탄설폰산으로 산성화하고, 이어 감압하에서 증발 건조시켰다. 잔류 기름을 아세토니트릴-에테르로 결정화하고, 결과 얻어진 조잡한 고체를 메탄올에 녹였다. 이 용액을 활성탄으로 처리하고 여과했다. 여액을 증발시켜 기름을 얻고, 이것을 아세토니트릴과 아세톤으로 혼합물에 현탁시켜 조잡한 고체를 얻었다. 메탄올-에테르로 재결정하고 95℃/0.1mm에서 48시간 건조시켜, 융점 202-204℃의 1,10-비스-[4-(P-클로로페닐아미노-1-피리디늄]데칸 설포네이트 18.4g을 얻었다.B. The methanol solution of the corresponding anhydrous base prepared from the dibromide according to the method of Example 76B was acidified with methanesulfonic acid and then evaporated to dryness under reduced pressure. The residual oil was crystallized with acetonitrile-ether and the resulting crude solid was dissolved in methanol. This solution was treated with activated charcoal and filtered. The filtrate was evaporated to give an oil which was suspended in the mixture with acetonitrile and acetone to give a crude solid. Recrystallized from methanol-ether and dried for 48 hours at 95 ° C./0.1 mm to obtain 18.4 g of 1,10-bis- [4- (P-chlorophenylamino-1-pyridinium] decane sulfonate at a melting point of 202-204 ° C. Got it.

[실시예 80]Example 80

4-(P-클로로 페닐아미노) 피리딘 10.0g(0.04몰)을 함유한 아세토니트릴 275ml와 N,N-디메틸포름아미드 100ml의 혼합물 용액을 교반하고 가온한 후, 1,5-디브로모펜탄 5.75g(0.025몰)의 아세토니트릴(25ml)용액을 적가했다. 이 혼합물을 환류하에서 24시간 가열했다. 반응 혼합물을 감압하에서 증발건조시키고, 잔사를 에테르와 아세토니트릴로 연화했다. 결과 생성된 엷은 황색의 고체를 에탄올에 재용해하여 얻은 용액을 할성탄으로 처리한 후 여과했다. 여액을 감압하에서 증발 건조시키고, 잔류 기름을 에테르-아세토니트릴로 결정화시켰다. 무색 고체를 메탄올 -아세토니트릴로 재결정화하고 115℃/0.1mm에서 48시간 건조시켜, 융점 166-168℃인 1,5-비스-[4-(P-클로로 페닐아미노)-1-피리디늄]펜탄 디브로마이드 8.1g을 얻었다.A mixture solution of 275 ml of acetonitrile containing 10.0 g (0.04 mol) of 4- (P-chloro phenylamino) pyridine and 100 ml of N, N-dimethylformamide was stirred and warmed, and then 1,5-dibromopentane 5.75 g (0.025 mol) of acetonitrile (25 ml) solution was added dropwise. This mixture was heated at reflux for 24 hours. The reaction mixture was evaporated to dryness under reduced pressure and the residue was triturated with ether and acetonitrile. The resulting pale yellow solid was redissolved in ethanol, and the resulting solution was treated with split coal and filtered. The filtrate was evaporated to dryness under reduced pressure and the residual oil was crystallized from ether-acetonitrile. The colorless solid was recrystallized from methanol-acetonitrile and dried for 48 hours at 115 ° C./0.1 mm to give 1,5-bis- [4- (P-chloro phenylamino) -1-pyridinium] having a melting point of 166-168 ° C. 8.1 g of pentane dibromide was obtained.

[실시예 81]Example 81

N,N-디메틸포름아미드 125ml와 아세토니트릴 50ml의 혼합물중에 4-(P-클로로페닐아미노)피리딘 10.0g(0.049몰)을 함유한 용액을 교반하고 가온한 후, 여기에 1,7-디브로모헵탄 6.45g의 아세토니트릴(25ml)용액을 적가하고, 이 혼합물을 환류하에서 19시간 가열했다. 반응 혼합물을 감압하에서 증발건조시키고, 잔류 기름을 에탄올-아세토니트릴로 결정화시켰다. 이렇게 생성된 고체를 메탄올에 녹이고 그 결과 얻은 용액을 활성탄으로 처리한 후 여과했다. 여액을 진공하에서 증발 건조시키고, 잔류 기름을 에탄올-아세토니트릴로 다시 결정화시켰다. 여과하여 모은 생성물을 105℃/0.1mm에서 36시간 건조시켜, 융점 202-204℃인 1,7-비스-[4-(P-클로로 페닐아미노)-1-피리디늄]헵탄 디브로마이드 10.4g을 얻었다.In a mixture of 125 ml of N, N-dimethylformamide and 50 ml of acetonitrile, a solution containing 10.0 g (0.049 mol) of 4- (P-chlorophenylamino) pyridine was stirred and warmed, followed by 1,7-dibro 6.45 g of acetonitrile (25 ml) solution of moheptane was added dropwise, and the mixture was heated at reflux for 19 hours. The reaction mixture was evaporated to dryness under reduced pressure and the residual oil was crystallized from ethanol-acetonitrile. The solid thus produced was dissolved in methanol, and the resulting solution was treated with activated carbon and filtered. The filtrate was evaporated to dryness in vacuo and the residual oil was crystallized again with ethanol-acetonitrile. The collected product was dried for 36 hours at 105 ° C./0.1 mm to obtain 10.4 g of 1,7-bis- [4- (P-chlorophenylamino) -1-pyridinium] heptane dibromide having a melting point of 202-204 ° C. Got it.

[실시예 82]Example 82

4-(P-클로로페닐아미노)피리딘 10.0g(0.049몰)과 1,9-디브로모노난 7.15g(0.025몰)을 사용한 것을 제외하고는 실시예 81에서와 유사한 방법으로 반응시켜, 융점 178-179℃인 1,9-비스-[4-(P-클로로페닐아미노)-1-피니디늄]노난 디브로마이드 11.2g을 얻었다 상기의 실시예들과 유사한 방법으로 다음의 비스-[4-(R-아미노)-1-피리디늄]알칸을 얻었다. 즉,Melting point 178 by reaction in a similar manner as in Example 81, except that 10.0 g (0.049 mol) of 4- (P-chlorophenylamino) pyridine and 7.15 g (0.025 mol) of 1,9-dibromononane were used. 11.2 g of 1,9-bis- [4- (P-chlorophenylamino) -1-pinidinium] nonane dibromide at -179 ° C was obtained, and the following bis- [4- ( R-amino) -1-pyridinium] alkane was obtained. In other words,

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 테트라데실아민 하이드로클로라이드와 반응시켜 4-(테트라데실아미노) 피리딘을 얻고, 이어 이것과 1,6-디브로모-3-에틸헥산을 반응시켜 3-에틸-1,6-비스- [4-(테트라데실아미노)-1-피리디늄] 헥산 디브로아이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride was reacted with tetradecylamine hydrochloride to give 4- (tetradecylamino) pyridine, followed by 1,6-dibromo-3-ethylhexane The reaction was carried out to obtain 3-ethyl-1,6-bis- [4- (tetradecylamino) -1-pyridinium] hexane dibroide.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 옥타데실아민 하이드로클로라이드와 반응시켜 4-(옥타데실아미노)피리딘을 얻고, 이어 이것과 1,5-디브로모펜탄을 반응시켜 1,5-비스-[4-(옥타데실아미노)-1-피리디늄] 헥산 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride was reacted with octadecylamine hydrochloride to obtain 4- (octadecylamino) pyridine, which was then reacted with 1,5-dibromopentane to give 1, 5-bis- [4- (octadecylamino) -1-pyridinium] hexanes dibromide was obtained.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 2,2-디메틸부틸아민 하이드로클로라이드와 반응시켜 4-(2,2-디메틸부틸아미노)피리딘을 얻고, 이어 이것과 1,11-디브로모-3-메틸운데칸을 반응시켜 1,11-비스-[4-(2,2-디메틸부틸아미노)-1-피리디늄]-3-메틸운데칸 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with 2,2-dimethylbutylamine hydrochloride to give 4- (2,2-dimethylbutylamino) pyridine, followed by 1,11-di Bromo-3-methyl undecane was reacted to obtain 1,11-bis- [4- (2,2-dimethylbutylamino) -1-pyridinium] -3-methyl undecane dibromide.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 1,4-디메틸펜틸아민 하이드로클로라이드와 반응시켜 4-(1,4-디메틸펜틸아미노)피리딘을 얻고, 이어 이것과 1,18-디브로모옥 타데칸을 반응시켜 1,18-비스-[4-(1,4-디메틸펜틸아미노)-1-피리디늄]옥타데칸 디브로 마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with 1,4-dimethylpentylamine hydrochloride to give 4- (1,4-dimethylpentylamino) pyridine, followed by 1,18-di Bromoocta tadecane was reacted to obtain 1,18-bis- [4- (1,4-dimethylpentylamino) -1-pyridinium] octadecane dibromide.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 1,5-디메틸-4-에틸아헥실민 하이드로클로라이드와 반응시켜 4-(1,5-디메틸-4-에틸헥실아미노)피리딘을 얻고, 이어 이것과 1,12-디브로모-4,9-디메틸도데칸을 반응시켜 4,9-디메틸-1,12-비스-[4-(1,5-디메틸-4-에틸헥실아미노)-1-피리디늄]도데칸 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with 1,5-dimethyl-4-ethylhexylmin hydrochloride to give 4- (1,5-dimethyl-4-ethylhexylamino) pyridine, This was then reacted with 1,12-dibromo-4,9-dimethyldodecane to give 4,9-dimethyl-1,12-bis- [4- (1,5-dimethyl-4-ethylhexylamino)- 1-pyridinium] dodecane dibromide was obtained.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 1,4-(사이클로펜틸아미노)피리딘을 얻고, 이어 이것과 1,10-디클로로데칸을 반응시켜 1,10-비스-[4-(사이클로펜틸아미노)-1-피리디늄]데칸 디클로라이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride was obtained with 1,4- (cyclopentylamino) pyridine, and then reacted with 1,10-dichlorodecane to give 1,10-bis- [4- ( Cyclopentylamino) -1-pyridinium] decane dichloride was obtained.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 사이클로헵틸아민 하이드로클로라이드와 반응시켜 4-(사이클로헵틸아미노)피리딘을 얻고, 이어 이것과 1,12-디브로모 옥타데칸을 반응시켜 1,12-비스-[4-(사이클로헵틸아미노)-1-피리디늄]도데칸 디클로라이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with cycloheptylamine hydrochloride to give 4- (cycloheptylamino) pyridine, followed by reaction with 1,12-dibromo octadecane 1 , 12-bis- [4- (cycloheptylamino) -1-pyridinium] dodecane dichloride was obtained.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 P-브로모아닐린 하이드로클로라이드와 반응시켜 4-(P-브로모페닐아미노)피리딘을 얻고, 이어 이것과 1,6-디브로모-3-메틸헥산을 반응시켜 1,6-비스-[4-(P-브로모페닐아미노)-1-피리디늄]-3-메틸헥산 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with P-bromoaniline hydrochloride to give 4- (P-bromophenylamino) pyridine, followed by 1,6-dibromo- 3-methylhexane was reacted to obtain 1,6-bis- [4- (P-bromophenylamino) -1-pyridinium] -3-methylhexane dibromide.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 m-플루오로 아닐린 하이드로클로라이드와 반응시켜 4-(m-플루오로페닐아미노)피리딘을 얻고, 이어 이것과 1,10-디브로모데칸을 반응시켜 1,10-비스-[4-(m-플루오로페닐아미 노)-1-피리디늄]데칸 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with m-fluoro aniline hydrochloride to give 4- (m-fluorophenylamino) pyridine, followed by 1,10-dibromodecane The reaction was carried out to obtain 1,10-bis- [4- (m-fluorophenylamino) -1-pyridinium] decane dibromide.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 3-클로로-4-플루오로아닐린 하이드로클로라이드와 반응시켜 4-(3-클로로-4-플루오로 페닐아미노)피리딘을 얻고, 이어 이것과 1,4-디브로모-2-에틸부탄을 반응시켜 1,4-비스-[4-(3-클로로-4-플루오로페닐아미노)-1-피리디늄-2-에틸부탄 디브로마이드를 얻었다. 1,10-디클로로데탄을 4-(밴질아미노)피리딘과 반응시켜 1,10-비스-[4-(벤질아미노)-1-피리디늄]데칸 디클로라로드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride is reacted with 3-chloro-4-fluoroaniline hydrochloride to give 4- (3-chloro-4-fluoro phenylamino) pyridine, followed by 1,4-dibromo-2-ethylbutane was reacted to obtain 1,4-bis- [4- (3-chloro-4-fluorophenylamino) -1-pyridinium-2-ethylbutane dibromide . 1,10-dichlorodecane was reacted with 4- (benzylamino) pyridine to give 1,10-bis- [4- (benzylamino) -1-pyridinium] decane dichlororod.

N-(4-피리딜)-피리디늄 클로라이드 하이드로클로라이드를 3,4-메틸렌디옥시아닐린 하이드로클로라이드와 반응시켜 4-(3,4-메틸렌디 옥시페닐아미노)피리딘을 얻고, 이어 이것과 1,8-디브로모옥탄을 반응시켜 1,8-비스-[4-(3,4-메틸렌디옥시페닐아미노-1-피리디늄]옥탄 디브로마이드를 얻었다.N- (4-pyridyl) -pyridinium chloride hydrochloride was reacted with 3,4-methylenedioxyaniline hydrochloride to obtain 4- (3,4-methylenedioxyphenylamino) pyridine, followed by 1, 8-dibromooctane was reacted to obtain 1,8-bis- [4- (3,4-methylenedioxyphenylamino-1-pyridinium] octane dibromide.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 P-에틸아닐린 하이드로클로라이드와 반응시켜 4-(P-에닐페닐아미노)피리딘을 얻고, 이어 이것과 1,9-디브로모노난을 반응시켜 1,9-비스-[4-(P-에틸페닐아미노)-1-피리디늄노난 디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with P-ethylaniline hydrochloride to obtain 4- (P-enylphenylamino) pyridine, which is then reacted with 1,9-dibromononane 1,9-bis- [4- (P-ethylphenylamino) -1-pyridiniumnonane dibromide was obtained.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 P-아니시딘 하이드로클로라이드와 반응시켜 4-(P-메톡시페닐아미노)피리딘을 얻고, 이어 이것과 1,10-디클로로데칸을 반응시켜 1,10--비스-[4-(P-메톡시페닐아미노)-1-피리디늄]데칸 디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with P-anisidine hydrochloride to give 4- (P-methoxyphenylamino) pyridine, which is then reacted with 1,10-dichlorodecane to give 1 , 10-bis- [4- (P-methoxyphenylamino) -1-pyridinium] decane dichloride was obtained.

N-(4-피리딜)피리디늄 클로로라이드 하이드로클로라이드를 m-플루오로 아닐린 하이드로크로라이드와 반응시켜 4-(m-니트로페닐아미노)피리딘을 얻고, 이어 이것과 1,11-디브로모데칸을 반응시켜 1,11-비스-[4-(m-니트로페닐아미노)-1-피리디늄]운데칸 디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chlorolide hydrochloride is reacted with m-fluoro aniline hydrochloride to give 4- (m-nitrophenylamino) pyridine, followed by 1,11-dibromodecane The reaction was carried out to obtain 1,11-bis- [4- (m-nitrophenylamino) -1-pyridinium] undecane dibromide.

N-(4-피리딜)피리디늄 클로로라이드 하이드로클로라이드를 0-시아노 아닐린 하이드로클로라이드와 반응시켜 4-(0-시아노페닐아미노)피리딘을 얻고, 이어 이것과 1,12-디브로모도데칸을 반응시켜 1,12-비스-[4-(0-시아노페닐아미노)-1-피리디늄]도데칸 디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chlorolide hydrochloride is reacted with 0-cyano aniline hydrochloride to give 4- (0-cyanophenylamino) pyridine, followed by 1,12-dibromododecane Was reacted to obtain 1,12-bis- [4- (0-cyanophenylamino) -1-pyridinium] dodecane dibromide.

N-(4-피리딜)피리디늄 클로로라이드 하이드로클로라이드를 m-(트리플루오로메틸)아닐린 하이드로클로라이드와 반응시켜 4-[m-(트리플루오로메틸)페닐아미노)피리딘을 얻고, 이어 이것과 1,16-디브로모 헥사데칸을 반응시켜 1,16-비스-[4-[m-(트리플루오로메틸)페닐아미노)-1-피리디늄]헥사데칸 디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chlorolide hydrochloride was reacted with m- (trifluoromethyl) aniline hydrochloride to give 4- [m- (trifluoromethyl) phenylamino) pyridine, 1,16-dibromo hexadecane was reacted to obtain 1,16-bis- [4- [m- (trifluoromethyl) phenylamino) -1-pyridinium] hexadecane dibromide.

N-(4-피리딜)피리디늄 클로로라이드 하이드로클로라이드를 2-메톡시-5-메틸아닐린 하이드로클로라이드와 반응시켜 4-(2-메톡시-5-메틸페닐아미노)피리딘을 얻고, 이어 이것과 1,7-디브로모헵탄을 반응시켜 1,7-비스-[4-(2-메톡시-5-메틸페닐아미노)-1-피리디늄]헵탄 디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chlorolide hydrochloride is reacted with 2-methoxy-5-methylaniline hydrochloride to give 4- (2-methoxy-5-methylphenylamino) pyridine, followed by 1 , 7-dibromoheptane was reacted to obtain 1,7-bis- [4- (2-methoxy-5-methylphenylamino) -1-pyridinium] heptane dibromide.

상술한 방법에 따라 제조한 구조식(I)의 비스-[4-(R-아미노-1-피리디늄]알칸류 구체적인 예를 다음에 표시했다.Specific examples of bis- [4- (R-amino-1-pyridinium] alkanes of the formula (I) prepared according to the above-described method are shown below.

3-메틸-1,5-비스[4-운데실아미노)-1-피리디늄]펜탄 디브로마이드, 3-메틸-1,5-비스[4-트리데실아미노)-1-피리디늄]펜탄 디클로라이드, 4,4-디메틸-1,7-비스-[4-(펜타데실아미노)-1-피리디늄]헨탄 설페이트, 2,6-디메틸-1,7-비스-[4-(헥사데실아미노)-1-피리디늄)헵탄 디설파메이트, 1-메틸-1,4-비스-[4-헵타데실아미노)-1-피리디늄]부탄 디벤젠설포네이트, 2,4,4-트리메틸-1,6-비스-[4-(2-메틸헥실아미노)-1-피리디늄]헥산 비스-사이클로 헥실설파메이트, 1,17-비스-[4-(3-에틸펜틸아미노)-1-피리디늄]헵타데칸 디브로마이드, 1,16-비스-[4-(1-(에틸헥실아미노)-1-피리디늄]헥사데칸 디나이트레이트, 1,15-비스-[4-(헵틸아미노)-1-피리디늄]펜타데칸 디브로마이드, 1,13-비스-[4-(옥틸아미노)-1-피리디늄]트리데칸 디-2-나프탈렌설포네이트, -1,11-비스-[4-(3에틸헵틸아미노)-1-피리디늄)운데칸 2,6-나프탈렌설포네이트, 4-메틸-1,14-비스-[4-(2-프로필펜틸아미노)-1-피리디늄)테트라데칸 디클로라이드, 5-에틸-1,9-비스-[4(1,3,5-트리메틸헥실아미노)-1-피리디늄]노난 디브로마이드, 3,3,6,6-테트라메틸-1,8-비스-[4-(헵틸아미노(-1-피리디늄]옥탄 디브로마이드, 2,13-디메틸-1,14-비스[4-(1,2-디메틸테트라데실아미노)-1-피리디늄] 테트라데실디브로마이드, 1,6-비스-[4-(1-메틸펜틸아미노)-1-피리디늄]헥산디-P-톨루엔설포네이트, 1,8-비스-[4-(2-메틸헵틸아미노)-1-피리디늄]옥탄디아이오다이드, 1,8-비스-[4-(2-메틸-3-에틸펜틸아미노)-1-피리디늄]옥탄디에탄설포네이트, 1,9-비스-[4-(0-클로로페닐아미노)-1-피리디늄]노난디브로마이드, 1,8-비스-[4-(P-아이오도페닐아미노)-1-피리디늄]옥탄디아이오아이드, 1,12-비스-[4-(2,4-디플루오로페닐아미노)-1-피리디늄]도데칸디브로마이드, 1,11-비스-[4-(2,5-디브로모페닐아미노)-1-피리디늄]운데칸디브로마이드, 1,10-비스-[4-(3,5-디클로로페닐아미노)-1-피리디늄]데칸디클로라이드, 1,8-비스-[4-(2-플루오로벤질아미노)-1-피리디늄]옥탄디클로라이드, 1,18-비스-[4-(3,4-디클로로벤질아미노)-1-피리디늄]옥타데칸디브로마이드, 1,4-비스-[4-(4-하이드록시-3-메톡시벤질아미노)-1-피리디늄]부탄디브로마이드 및 1,12-비스[4-(4-메틸벤질아미노)-1-피리디늄]도데칸디브로마이드.3-methyl-1,5-bis [4-undecylamino) -1-pyridinium] pentane dibromide, 3-methyl-1,5-bis [4-tridecylamino) -1-pyridinium] pentane di Chloride, 4,4-dimethyl-1,7-bis- [4- (pentadecylamino) -1-pyridinium] hentane sulfate, 2,6-dimethyl-1,7-bis- [4- (hexadecylamino ) -1-pyridinium) heptane disulfamate, 1-methyl-1,4-bis- [4-heptadecylamino) -1-pyridinium] butane dibenzenesulfonate, 2,4,4-trimethyl-1 , 6-bis- [4- (2-methylhexylamino) -1-pyridinium] hexane bis-cyclohexylsulfamate, 1,17-bis- [4- (3-ethylpentylamino) -1-pyridinium ] Heptadecane dibromide, 1,16-bis- [4- (1- (ethylhexylamino) -1-pyridinium] hexadecane dinitrate, 1,15-bis- [4- (heptylamino) -1 -Pyridinium] pentadecane dibromide, 1,13-bis- [4- (octylamino) -1-pyridinium] tridecane di-2-naphthalenesulfonate, -1,11-bis- [4- (3 Ethylheptylamino) -1-pyridinium) undecane 2,6- Naphthalenesulfonate, 4-methyl-1,14-bis- [4- (2-propylpentylamino) -1-pyridinium) tetradecane dichloride, 5-ethyl-1,9-bis- [4 (1, 3,5-trimethylhexylamino) -1-pyridinium] nonane dibromide, 3,3,6,6-tetramethyl-1,8-bis- [4- (heptylamino (-1-pyridinium] octane di Bromide, 2,13-dimethyl-1,14-bis [4- (1,2-dimethyltetradecylamino) -1-pyridinium] tetradecyldibromide, 1,6-bis- [4- (1-methyl Pentylamino) -1-pyridinium] hexanedi-P-toluenesulfonate, 1,8-bis- [4- (2-methylheptylamino) -1-pyridinium] octane diiodide, 1,8-bis -[4- (2-methyl-3-ethylpentylamino) -1-pyridinium] octanediethanesulfonate, 1,9-bis- [4- (0-chlorophenylamino) -1-pyridinium] no Nadibromide, 1,8-bis- [4- (P-iodophenylamino) -1-pyridinium] octane diioide, 1,12-bis- [4- (2,4-difluorophenylamino ) -1-pyridinium] dodecanedibromide, 1,11- S- [4- (2,5-dibromophenylamino) -1-pyridinium] undecandibromide, 1,10-bis- [4- (3,5-dichlorophenylamino) -1-pyridinium] Decandichloride, 1,8-bis- [4- (2-fluorobenzylamino) -1-pyridinium] octanedichloride, 1,18-bis- [4- (3,4-dichlorobenzylamino)- 1-pyridinium] octadecanedibromide, 1,4-bis- [4- (4-hydroxy-3-methoxybenzylamino) -1-pyridinium] butanedibromide and 1,12-bis [4- (4-methylbenzylamino) -1-pyridinium] dodecanedibromide.

[실시예 83]Example 83

4-(헵틸아미노)피리딘 11.52g(0.06몰)을 함유한 아세토니트릴(100ml)용액을 가온하고 교반한 후,

Figure kpo00023
,
Figure kpo00024
'-디브로모-P-크실렌 7.92g(0.03몰)의 아세토니트릴(150ml)용액을 소량씩 적가했다. 첨가가 끝난후 다량의 무색 결정을 용액으로 부터 분리시켰다. 반응혼합물을 환루하에서 6시간 가열했다. 실온으로 냉각한 후 고체 생성물을 여과하여 모으고, 아세토니트릴-에테르로 새척한 후, 앞서 얻어진 생성물 3.1g과 함해서 100℃/0.1mm에서 28시간 건조시켜, 융점 297-298℃인
Figure kpo00025
,
Figure kpo00026
'-비스-[4-(헵틸아미노)-피리디늄]-P-크실렌디브로마이드 22.0g을 얻었다.After acetonitrile (100 ml) solution containing 11.52 g (0.06 mol) of 4- (heptylamino) pyridine is warmed and stirred,
Figure kpo00023
,
Figure kpo00024
7.92 g (0.03 mol) of acetonitrile (150 ml) of '-dibromo-P-xylene was added dropwise in small portions. After the addition was completed, a large amount of colorless crystals were separated from the solution. The reaction mixture was heated under reflux for 6 hours. After cooling to room temperature, the solid product was collected by filtration, carburized with acetonitrile-ether, and then dried at 100 ° C./0.1 mm with 3.1 g of the previously obtained product for 28 hours to obtain a melting point of 297-298 ° C.
Figure kpo00025
,
Figure kpo00026
22.0 g of '-bis- [4- (heptylamino) -pyridinium] -P-xylenedibromide was obtained.

[실시예 81]Example 81

4-(헥실아미노)피리딘 11.6g(0.065몰)과

Figure kpo00027
,
Figure kpo00028
'-디브로모-P-크실렌 8.7g(0.033)몰을 사용하고 반응 혼합물을 20시간동안 환류시킨 것을 제외하고는 실시예 83에서와 유사하게 반응시켜, 융점 313-315℃인
Figure kpo00029
,
Figure kpo00030
'-비스-[4-(헥실아미노)피리디늄]-P-크실렌디 브로마이드 19.3g을 얻었다.11.6 g (0.065 mol) of 4- (hexylamino) pyridine
Figure kpo00027
,
Figure kpo00028
The reaction was conducted in a similar manner as in Example 83 except that 8.7 g (0.033) mole of '-dibromo-P-xylene was used and the reaction mixture was refluxed for 20 hours, and the melting point was 313-315 ° C.
Figure kpo00029
,
Figure kpo00030
19.3 g of '-bis- [4- (hexylamino) pyridinium] -P-xylenedi bromide was obtained.

[실시예 85]Example 85

4-아미노피리딘 19g과

Figure kpo00031
,
Figure kpo00032
'-디클로로-2,3,5,6-테트라메틸-P-크실렌 23g을 메탄올 600ml에 현탁시키고, 이 현탁액을 완전 용액의 되도록 증기욕상에서 가열했다. 소량의 불용성 물질을 여과한 후 맑은 용액을 증기욕에서 2시간 가온하였을 때 흰색고체가 분리되기 시작했다. 반응혼합ㅁ루을 실온까지 냉각하고, 고형 생성물을 여과하여 모은후 메탄올 및 에테르로 세척하고 100℃ 진공하에서 24시간 건조시켜, 융점이 340℃ 이상인
Figure kpo00033
,
Figure kpo00034
'-비스-(4-아미노-1-피리디늄)-2,3,5,6-테트라메틸-P-크실렌디클로라이드 29g을 얻었다.19 g of 4-aminopyridine and
Figure kpo00031
,
Figure kpo00032
23 g of '-dichloro-2,3,5,6-tetramethyl-P-xylene were suspended in 600 ml of methanol, and the suspension was heated in a steam bath so as to be a complete solution. After filtering a small amount of insoluble material, the white solid began to separate when the clear solution was warmed in a steam bath for 2 hours. The reaction mixture was cooled to room temperature, the solid product was collected by filtration, washed with methanol and ether, dried under vacuum at 100 ° C. for 24 hours, and the melting point was 340 ° C. or higher.
Figure kpo00033
,
Figure kpo00034
29 g of '-bis- (4-amino-1-pyridinium) -2,3,5,6-tetramethyl-P-xylenedichloride was obtained.

[실시예 86]Example 86

4-아미노피리딘 12.5g(0.132몰)을 함유한 뜨거운 2-프로판올 100ml용액에

Figure kpo00035
,
Figure kpo00036
'-디클로로--P-크실렌 11.6g(0.066몰)을 가하고, 이어 메탄올 400ml를 가했다. 혼합물을 완전 용액이 될때까지 가열했다. 불용성 물질소량을 여과한 후, 맑은 용액을 에틸아세테이느 500ml로 희석하여 실온으로 냉각했다. 고형 생성물을 여과하여 모으고 에틸아세테이트로 세척한 후, 건조시켜, 융점 332-335℃인
Figure kpo00037
,
Figure kpo00038
'-비스-(4-아미노-1-피리디늄)-P-크실렌디클로라이드 16g을 얻었다.In 100 ml of hot 2-propanol solution containing 12.5 g (0.132 mol) of 4-aminopyridine
Figure kpo00035
,
Figure kpo00036
11.6 g (0.066 mol) of '-dichloro-P-xylene was added followed by 400 ml of methanol. The mixture was heated until complete solution. After filtering a small amount of insoluble matter, the clear solution was diluted with 500 ml of ethyl acetate and cooled to room temperature. The solid product was collected by filtration, washed with ethyl acetate and dried to give a melting point of 332-335 ° C.
Figure kpo00037
,
Figure kpo00038
16 g of '-bis- (4-amino-1-pyridinium) -P-xylenedichloride was obtained.

상기 방법에 따라 제조한 구조식(II)의

Figure kpo00039
,
Figure kpo00040
'-비스-[4-(R-아미노)-1-피리디늄]크실렌의 구체적인 예를 다음에 표시했다.
Figure kpo00041
,
Figure kpo00042
'-디브로모-P-크실렌을 4-(에틸아미노) 피리딘과 반응시켜
Figure kpo00043
,
Figure kpo00044
'-비스-[4-(에틸아미노)-1-피리디늄]-P-크실렌디브로마이드를 얻었다.Of structural formula (II) prepared according to the above method
Figure kpo00039
,
Figure kpo00040
Specific examples of '-bis- [4- (R-amino) -1-pyridinium] xylene are shown next.
Figure kpo00041
,
Figure kpo00042
'-Dibromo-P-xylene is reacted with 4- (ethylamino) pyridine
Figure kpo00043
,
Figure kpo00044
'-Bis- [4- (ethylamino) -1-pyridinium] -P-xylenedibromide was obtained.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 2-에틸헥실아민 하이드로클로라이드와 반응시켜 4-(2-에틸헥실아미노)피리딘(비점 : 145- 150℃/0.9mm)을 얻고, 이어 이것과

Figure kpo00045
,
Figure kpo00046
'-디클로로-P-크실렌을 반응시켜
Figure kpo00047
,
Figure kpo00048
'-비스-[4-(2-에틸헥실아미노)-1-피리디늄]-P-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with 2-ethylhexylamine hydrochloride to give 4- (2-ethylhexylamino) pyridine (boiling point: 145-150 ° C./0.9 mm). and
Figure kpo00045
,
Figure kpo00046
By reacting '-dichloro-P-xylene
Figure kpo00047
,
Figure kpo00048
'-Bis- [4- (2-ethylhexylamino) -1-pyridinium] -P-xylenedichloride was obtained.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 n-데실아민 하이드로클로라이드와 반응시켜 4-(데실아미노)피리딘(융점 : 71-73℃)을 얻고, 이어 이것과

Figure kpo00049
,
Figure kpo00050
'-디클로로-P-크실렌을 반응시켜
Figure kpo00051
,
Figure kpo00052
'-비스-[4-(데실아미노)-1-피리디늄]-P-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with n-decylamine hydrochloride to obtain 4- (decylamino) pyridine (melting point: 71-73 ° C.), followed by
Figure kpo00049
,
Figure kpo00050
By reacting '-dichloro-P-xylene
Figure kpo00051
,
Figure kpo00052
'-Bis- [4- (decylamino) -1-pyridinium] -P-xylenedibromide was obtained.

Figure kpo00053
,
Figure kpo00054
'-디클로로-P-크실렌을 4-(도데실아미노)피리딘과 반응시켜
Figure kpo00055
,
Figure kpo00056
'-비스-[4-(도데실아미노)-1-피리디늄]-P-크실렌디클로라이드를 얻었다.
Figure kpo00053
,
Figure kpo00054
'-Dichloro-P-xylene is reacted with 4- (dodecylamino) pyridine
Figure kpo00055
,
Figure kpo00056
'-Bis- [4- (dodecylamino) -1-pyridinium] -P-xylenedichloride was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 옥타데실아민 하이드로클로라이드와 반응시켜 4-(옥타데실아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00057
,
Figure kpo00058
'-디브로모-P-크실렌을 반응시켜
Figure kpo00059
,
Figure kpo00060
'-비스-[4-(옥타데실아미노)-1-피리디늄]-P-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with octadecylamine hydrochloride to obtain 4- (octadecylamino) pyridine, which is followed by
Figure kpo00057
,
Figure kpo00058
'-Dibromo-P-xylene reacted
Figure kpo00059
,
Figure kpo00060
'-Bis- [4- (octadecylamino) -1-pyridinium] -P-xylenedibromide was obtained.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 데트라데실아민 하이드로클로라이드와 반응시켜 4-(데트라데실아미노) 피리딘(융점 : 91-93℃)을 얻고, 이어 이것과

Figure kpo00061
,
Figure kpo00062
'-디브로모-m-크실렌을 반응시켜
Figure kpo00063
,
Figure kpo00064
'-비스-[4-(데트라데실아미노)-1-피리디늄]-m-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with detradecylamine hydrochloride to obtain 4- (detradecylamino) pyridine (melting point: 91-93 ° C.), followed by
Figure kpo00061
,
Figure kpo00062
'-Dibromo-m-xylene reacted
Figure kpo00063
,
Figure kpo00064
'-Bis- [4- (detradecylamino) -1-pyridinium] -m-xylenedibromide was obtained.

Figure kpo00065
,
Figure kpo00066
'-디브로모-0-크실렌을 4-(부틸아미노) 피리딘과 반응시켜
Figure kpo00067
,
Figure kpo00068
'-비스-[4-(부틸아미노)-1-피리디늄]-0-크실렌디브로마이드를 얻었다.
Figure kpo00065
,
Figure kpo00066
'-Dibromo-0-xylene is reacted with 4- (butylamino) pyridine
Figure kpo00067
,
Figure kpo00068
'-Bis- [4- (butylamino) -1-pyridinium] -0-xylenedibromide was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 3-에틸헵틸아민 하이드로클로라이드와 반응시켜 4-(3-에틸헵틸아미노피리딘을 얻고 이어 이것과

Figure kpo00069
,
Figure kpo00070
'-디브로모-5-메틸-m-크실렌을 반응시켜
Figure kpo00071
,
Figure kpo00072
'-비스-4-(3-에틸헵틸아미노)-1-피리디늄]--5-메틸-m-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with 3-ethylheptylamine hydrochloride to obtain 4- (3-ethylheptylaminopyridine.
Figure kpo00069
,
Figure kpo00070
'-Dibromo-5-methyl-m-xylene is reacted
Figure kpo00071
,
Figure kpo00072
'-Bis-4- (3-ethylheptylamino) -1-pyridinium]-5-methyl-m-xylenedibromide was obtained.

N-(4-피리딜)피리디늄 클로라이드 하이드로클로라이드를 2-메틸헵틸아민 하이드로클로라이드와 반응시켜 4-(2-메틸헵틸아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00073
,
Figure kpo00074
'-디브로모-2,5-디메틸-P-크실렌을 반응시켜
Figure kpo00075
,
Figure kpo00076
'-비스-[4-(2-메틸헵틸아미노)-1-피리디늄]-2,5-디메틸-P-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with 2-methylheptylamine hydrochloride to obtain 4- (2-methylheptylamino) pyridine, which is followed by
Figure kpo00073
,
Figure kpo00074
'-Dibromo-2,5-dimethyl-P-xylene is reacted
Figure kpo00075
,
Figure kpo00076
'-Bis- [4- (2-methylheptylamino) -1-pyridinium] -2,5-dimethyl-P-xylenedibromide was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 n-옥틸아민 하이드로클로라이드와 반응시켜 4-(옥틸아미노) 피리딘(융점 ; 62-63℃)을 얻고, 이어 이것과

Figure kpo00077
,
Figure kpo00078
'-디클로로-2,4,6-트리메틸-m-크실렌을 반응시켜
Figure kpo00079
,
Figure kpo00080
'-비스-[4-(옥틸아미노)-1-피리디늄]-2,4,6-트리메틸-m-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with n-octylamine hydrochloride to obtain 4- (octylamino) pyridine (melting point; 62-63 ° C.), followed by
Figure kpo00077
,
Figure kpo00078
'-Dichloro-2,4,6-trimethyl-m-xylene is reacted
Figure kpo00079
,
Figure kpo00080
'-Bis- [4- (octylamino) -1-pyridinium] -2,4,6-trimethyl-m-xylenedichloride was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 2,2-디메틸아민 하이드로클로라이드와 반응시켜 4-(2,2-디메틸부틸아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00081
,
Figure kpo00082
',2-트리클로로-P-크실렌을 반응시켜
Figure kpo00083
,
Figure kpo00084
'-비스-[4-(2,2-디메틸부틸아미노)-1-피리디늄]-2-클로로-P-크실렌디클로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with 2,2-dimethylamine hydrochloride to give 4- (2,2-dimethylbutylamino) pyridine, which is followed by
Figure kpo00081
,
Figure kpo00082
', 2-trichloro-P-xylene is reacted
Figure kpo00083
,
Figure kpo00084
'-Bis- [4- (2,2-dimethylbutylamino) -1-pyridinium] -2-chloro-P-xylenedichloromide was obtained.

Figure kpo00085
,
Figure kpo00086
'-디브로모-4-클로로-0-크실렌올 4-(메틸아미노) 피리딘과 반응시켜
Figure kpo00087
,
Figure kpo00088
'-비스-[4-(메틸아미노)-1-피리디늄]-4-클로로-0-크실렌디브로마이드를 얻었다.
Figure kpo00085
,
Figure kpo00086
React with '-dibromo-4-chloro-0-xyleneol 4- (methylamino) pyridine
Figure kpo00087
,
Figure kpo00088
'-Bis- [4- (methylamino) -1-pyridinium] -4-chloro-0-xylenedibromide was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 2-프로필펜틸아민 하이드로클로라이드와 반응시켜 4-(2-프로필펜틸아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00089
,
Figure kpo00090
', 2,5-테트라클로로-P-크실렌을 반응시켜
Figure kpo00091
,
Figure kpo00092
'-비스-[4-(2-프로필펜틸아미노)-1-피리디늄]-2,5-디클로로-P-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with 2-propylpentylamine hydrochloride to give 4- (2-propylpentylamino) pyridine, which is followed by
Figure kpo00089
,
Figure kpo00090
', By reacting 2,5-tetrachloro-P-xylene
Figure kpo00091
,
Figure kpo00092
'-Bis- [4- (2-propylpentylamino) -1-pyridinium] -2,5-dichloro-P-xylenedichloride was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 1,1-디메틸운데실아민 하이드로클로라이드와 반응시켜 4-(1,1-디메틸운데실아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00093
,
Figure kpo00094
', 2,3,5-펜타클로로-P-크실렌을 반응시켜
Figure kpo00095
,
Figure kpo00096
'-비스-[4-(1,1-디메틸운데실아미노)-1-피리디늄]-2,3,5-트리클로로-P-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with 1,1-dimethylundecylamine hydrochloride to obtain 4- (1,1-dimethylundecylamino) pyridine, which is followed by
Figure kpo00093
,
Figure kpo00094
', 2,3,5-pentachloro-P-xylene is reacted
Figure kpo00095
,
Figure kpo00096
'-Bis- [4- (1,1-dimethylundecylamino) -1-pyridinium] -2,3,5-trichloro-P-xylenedichloride was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 n-노닐아민 하이드로클로라이드와 반응시켜 4-(노닐아미노) 피리딘(융점 ; 59-60℃)을 얻고, 이어 이것과

Figure kpo00097
,
Figure kpo00098
', 2,3,5,6-헥사클로로-P-크실렌을 반응시켜
Figure kpo00099
,
Figure kpo00100
'-비스-[4-(노닐아미노)-1-피리디늄]-2,3,5,6-테트라클로로-P-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride was reacted with n-nonylamine hydrochloride to obtain 4- (nonylamino) pyridine (melting point; 59-60 ° C.), followed by
Figure kpo00097
,
Figure kpo00098
', 2,3,5,6-hexachloro-P-xylene is reacted
Figure kpo00099
,
Figure kpo00100
'-Bis- [4- (nonylamino) -1-pyridinium] -2,3,5,6-tetrachloro-P-xylenedichloride was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 벤질아민과 반응시켜 4-(벤질아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00101
,
Figure kpo00102
'-디브로모-P-크실렌을 반응시켜
Figure kpo00103
,
Figure kpo00104
'-비스-[4-(벤질아미노)-1-피리디늄]-P-크실렌디브로마이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with benzylamine to obtain 4- (benzylamino) pyridine,
Figure kpo00101
,
Figure kpo00102
'-Dibromo-P-xylene reacted
Figure kpo00103
,
Figure kpo00104
'-Bis- [4- (benzylamino) -1-pyridinium] -P-xylenedibromide was obtained.

N-(4-피리딜) 피리디늄 클로라이드 하이드로클로라이드를 벤질아민과 반응시켜 4-(벤질아미노) 피리딘을 얻고, 이어 이것과

Figure kpo00105
,
Figure kpo00106
',2-트리클로로-P-크실렌을 반응시켜
Figure kpo00107
,
Figure kpo00108
'-비스-[4-(벤질아미노)-1-피리디늄]-2-클로로-P-크실렌디클로라이드를 얻었다.N- (4-pyridyl) pyridinium chloride hydrochloride is reacted with benzylamine to obtain 4- (benzylamino) pyridine,
Figure kpo00105
,
Figure kpo00106
', 2-trichloro-P-xylene is reacted
Figure kpo00107
,
Figure kpo00108
'-Bis- [4- (benzylamino) -1-pyridinium] -2-chloro-P-xylenedichloride was obtained.

구조식(I)의 화합물중 대표적인 화합물의 항균 및 항진균 활성을 고스(Goss)등에 의해 설명된 자동역가 검정봅(autotiter)[미생물학,16(9), 1414-1416(1968)]의 수정법으로 측정했으며, 여기서 시험화합물의 1000mcg/ml용액을 제조했다. 오토트레이(autotray)의 첫째 컵에 시험액 0.1ml을 가한다. 시험 화합물 용액 0.05ml를 마이크로타이터전이 루우프(microtiter transfer loop)로 제거한 후, 멸균수 0.05ml로 희석하는 조작으로부터 자동역가 검정기의 활동이 시작된다. 이 조작에 이어, 접종된 2중역가 반합성 배시(글루코우스) 0.05ml가 자동적으로 각 컵에 첨가된다. 이 조작결과, 최종 약물의 농도는 500-0.06mcg/ml로 ½감소된다. 오토트레이를 37℃에서 18-20시간 배양한 후, 혼탁도에 의한 성장을 육안으로 관찰한다. 성장이 나타나지 않은(즉, 혼탁도가 0인)그 계열의 마지막 샘플농도를 최소 발육저지농도(mcg/ml)로 한다. 화합물들을 용액상태로 하여, 스타플로코쿠스아우래우스(Staphylococcus aureus), 푸로테우스 마라빌리스(Proteus mirabilis), 에쉘리히아콜리(Escheria coli), 클렙시엘라뉴모니애(Klebseilla pneuminiae), 슈도모나스 에루기노자(Pseudomonas aeruginosa), 스트렙토코쿠스 파이오제네스(Streptococcus pyogense)를 포함한 여러종류의 그람 양성 및 음성 박테리아에 대해, 그리고 아스펠기루스 나이거(Aspergillus niger), 캔디다 알비칸(Candida albicans) 및 트리코피톤 멘타크로피테스(Trichophyton mentagrophytes)와 같은 진균에 대해 검사했다.The antimicrobial and antifungal activity of the representative compounds of the formula (I) were determined by the modification of the autotiter assay described by Goss et al. (Microbiology, 16 (9), 1414-1416 (1968)). Here, 1000 mcg / ml solution of the test compound was prepared. 0.1 ml of the test solution is added to the first cup of the autotray. The activity of the autotiter assay device is initiated by the operation of diluting 0.05 ml of the test compound solution with a microtiter transfer loop and then diluting with 0.05 ml of sterile water. Following this operation, 0.05 ml of inoculated double titer semisynthetic bash (glucose) is automatically added to each cup. As a result of this manipulation, the concentration of the final drug is ½ reduced to 500-0.06 mcg / ml. After incubating the auto tray for 18-20 hours at 37 ° C., growth by turbidity was visually observed. The final sample concentration of the series that showed no growth (ie, zero turbidity) is taken as the minimum growth inhibition concentration (mcg / ml). The compounds are in solution, Staphylococcus aureus, Proteus mirabilis, Escheria coli, Klebseilla pneuminiae, Pseudomonas Against a variety of Gram-positive and negative bacteria, including Pseudomonas aeruginosa, Streptococcus pyogense, and Aspergillus niger, Candida albicans and Fungi, such as Trichophyton mentagrophytes, were tested.

구조식(I)의 많은 화합물은 스트랩토코쿠스 뮤탄(Streptococcus mutan)과 악티노마이세스 A-비스코시스(Actinomyees A-viscosis)에 대해서도 항균효과를 나타냈다.Many compounds of formula (I) also exhibited antimicrobial effects against Streptococcus mutan and Actinomyes A-viscosis.

대표적인 화합물들의 단순포진형 2 바이러스(Herpes Simplex type 2 virus)에 대한 살균 바이러스 효과를 E.C헤르만[Jr. Proc. Soc. Exp. Biol. Med.107,142(1961)]이 발표한 DNA-함유 바이러스의 특수 억제인자의 검출법과 유사한 방법으로, 시험화합물 2mg을 배양배지 표면에 놓고 시험관내에서 검사했다. 그결과 실시예 3,5C,7,9C,10,11,13,17,18,21,22,24,31,33,35,36,37,53,54,55,56,57, 58,60, 61,63,81,82,83 및 84의 화합물은 활성이 있으며, 실시예 16,34,39,40 및 79B의 화합물은 불활성이라는 것이 발견되었다.The bactericidal virus effect on the herpes simplex type 2 virus of representative compounds is described by EC Herman [Jr. Proc. Soc. Exp. Biol. Med. 107, 142 (1961)] as published by the method similar to the detection of specific inhibitors of the DNA- containing viruses, place the test compound 2mg to the culture medium surface was examined in vitro. As a result, Examples 3,5C, 7,9C, 10,11,13,17,18,21,22,24,31,33,35,36,37,53,54,55,56,57,58, It was found that the compounds of 60, 61, 63, 81, 82, 83 and 84 are active and the compounds of Examples 16, 34, 39, 40 and 79B are inactive.

본 발명의 몇가지 화합물의 치구형성 억제효과는 이 화합물의 스트렙 토코쿠스뮤탄 OMZ-61(Streptococcus mutans OMZ 61)에 의한 치구형성을 억제하는 능력을 측정하는 다음의 방법에 따라 결정했다.The jigogenesis inhibitory effect of several compounds of the present invention was determined according to the following method for measuring the ability of the compound to inhibit jigogenesis by Streptococcus mutans OMZ 61.

치구 형성 스트렙토코쿠스 뮤탄 OMZ-61을 함유한 BBL우육 추출울 1.5g, 염화나트륨 5g, 탈수트립티 케이스 10g, 설탕 5g과 증류수를 충분량 가해 총용량 1000ml로 한 배양배지를 pH7.0으로 맞추고, 막여과(membrane filtration)하여 멸균화한다. 배지를 10ml씩 150×16mm 시험관내에 멸균적으로 나누어 넣고, 사용할 때까지 냉장온도를 보관한다.BBL beef extract containing jig-forming streptococcus mutan OMZ-61, 1.5 g of sodium chloride, 5 g of dehydrated trypti case, 5 g of sugar and distilled water were added, and the culture medium with a total volume of 1000 ml was adjusted to pH 7.0. (membrane filtration) to sterilize. The medium is sterilized in 10 x 150 x 16 mm test tubes and stored at refrigerated temperature until use.

증류수 1ml에 충분량의 0.1N 수산화마트륨, 10% 디메틸설폭사이드, 또는 10% N,N-디메틸포름아미드를 가하여 시험화합물 100mg을 용해시키고, 결과 생긴용액을 증류수를 가해 10ml로 하여 2개 농도의 시험화합물을 제조한다. 이 1.0% 용액 및 증류수내 1:10희석액(0.1%)을 사용하기 전에 막여과법으로 멸균화한다.To 1 ml of distilled water, 0.1 N of martium hydroxide, 10% dimethyl sulfoxide, or 10% N, N-dimethylformamide was added to dissolve 100 mg of the test compound, and the resulting solution was diluted to 10 ml with distilled water. Prepare the test compound. This 1.0% solution and 1:10 diluent (0.1%) in distilled water are sterilized by membrane filtration before use.

치구가 전혀 없는 전연치아 에나멜이나 합성 하이드록실 인회석의 멸균조각을 각 농도의 화합물에 1분씩 2번 현탁시키고, 각기 그 사이에 1분간 공기 건조시킨다. 각 조각을 멸균 증류수(세정액)가 함유된 각 시험관내에 현탁시키고 5분간 진탕한다. 이어 이들을 액체 우육추출배지(10ml)에 현탁시킨후,여기에 스트렙토코쿠스 뮤탄의 24시간 혐기성 배양액 0.3ml를 가한다. 이어, ＂처리된＂ 하이드록실 인회석과 스트렙 토코쿠스 뮤탄을 함유한 시험관을 37℃에서 24시간 혐기적으로 배양했다. 같은 방법으로 화합물 용액내에 1분씩 2번 침지시키고 그 사이에 각각 1분간 공기 건조시키고, 최종 5분간 세정을 반복한 후, 다시 한번 10%우육 추출배지 10ml와 접종물 0.3ml를 함유한 새로운 시험관에 하이드록실 인회석을 현탁시킨다. 24시간동안 다시한번 배양한 후, 하이드록실 인회석을 각 조각을 증류수가 함유된 3개의 연속 시험관내에서 1분간 세정한다. 이어 이것을 F, D, C적색 3호 염료 용액내에 1분간 현탁시킨다. 이 염색과정의 목적은 치구 형성 미생물에 48시간 노출시킨 이후의 치구의 전개를 좀더 쉽게 구별하기 위한 것이다. 과량의 염료를 제거하기 위해 10초간 세정한다. 치구가 형성된 경우에는 밝은 핑크색으로 착색된다. 사용된 농도 퍼센트에서 치구가 억제되었는가(활성), 안 되었는가(비활성)로 시험결과를 표시한다. 활성화합물의 최소 유효농도를 결정하기 위해 저농도에서 연속적으로 시험한다. 어떤 경우에는 하이드록실 인회석으로부터 화합물이 빠져나와 배지내에 항균 레벨을 만들고 그 결과 배양배지내의 미생물의 성장이 억제되기 때문에, 치구의 형성이 간섭을 받게된다. 이런 경우에는, 주위 배지내의 미생물의 성장이 약물 처리되지 않은 대조 배지에서와 동일할 정도의 저농도로 화합물을 시험한다.Sterilized pieces of toothbrush-free all tooth enamel or synthetic hydroxyl apatite are suspended in compounds of each concentration twice for 1 minute and air-dried for 1 minute between them. Each piece is suspended in each test tube containing sterile distilled water (cleaning solution) and shaken for 5 minutes. They are then suspended in liquid beef extraction medium (10 ml), and then 0.3 ml of a 24-hour anaerobic culture of Streptococcus mutan is added thereto. Subsequently, test tubes containing the “treated” hydroxyl apatite and Streptococcus mutan were incubated anaerobicly at 37 ° C. for 24 hours. In the same way, the solution was immersed twice in the compound solution twice for 1 minute, air-dried for 1 minute between them, and the washing was repeated for the last 5 minutes, and then again in a new test tube containing 10 ml of 10% beef extract medium and 0.3 ml of inoculum. Suspend hydroxyl apatite. After incubation for another 24 hours, the hydroxyl apatite is rinsed with each piece for 1 minute in three consecutive test tubes containing distilled water. This is then suspended in F, D, C red No. 3 dye solution for 1 minute. The purpose of this staining process is to more easily distinguish the development of jig after 48 hours of exposure to jig forming microorganisms. Rinse for 10 seconds to remove excess dye. If a jig is formed, it is colored bright pink. Indicate the test results as whether the fixture is inhibited (active) or not (inactive) at the percentage of concentration used. The test is conducted continuously at low concentrations to determine the minimum effective concentration of the active compound. In some cases, the formation of the jig interferes with the release of the compound from the hydroxyl apatite, creating an antimicrobial level in the medium, which in turn inhibits the growth of microorganisms in the culture medium. In this case, the compound is tested at low concentrations such that the growth of microorganisms in the surrounding medium is the same as in the non-drug control medium.

이와 같은 저농도에서는 치구가 형성될 수도 있고 형성되지 않을 수도 있다.At such low concentrations, a jig may or may not be formed.

치구형성을 방지하기 위히새 시험 화합물이 치아표면에 가하여진 경우에는 예컨대 커피, 담배, 착색음식과 같은 착색제가 치아표면에 축적될 가능성이 있다. 따라서 상기 방법은 착색 가능성, 즉시험 화합물에 의하여 치아표면에 착색제의 부착이 촉진되는 정도를 측정하는 방법으로도 이용된다. 즉, 최종 세정후 시험물 표면에 부착 잔류된 균일한 엷은 핑크색은 시험농도퍼센트에서의 착색 가능성을 나타내는 것으로서 착색농도로 표시된다. 시험 화합물에 기인된 균일한 엷은 핑크색은 치구 형성에 의한 밝은 핑크색과는 쉽게 구분된다. 일반적으로, 화합물의 염색농도는 치구 억제를 위한 최소 유효농도보다 상당히 높기 때문에 유리하다.If a new test compound is added to the tooth surface to prevent jig formation, there is a possibility that colorants, such as coffee, tobacco and colored food, may accumulate on the tooth surface. Therefore, the method is also used as a method of measuring the coloring potential, that is, the extent to which the adhesion of the coloring agent to the tooth surface by the test compound is promoted. That is, the uniform pale pink color remaining on the surface of the test article after the final cleaning is expressed as the coloring density as indicating the coloring possibility at the test concentration percentage. The uniform pale pink due to the test compound is easily distinguished from the bright pink due to jig formation. In general, the staining concentration of the compound is advantageous because it is significantly higher than the minimum effective concentration for jig inhibition.

이들 화합물의 항균, 항진균, 및 치구 억제시험의 숫자적 데이타를 다음 표A에 표시했다. 두개의 공지 화합물, 즉 1,8-비스-(4-아미노-1-피리디늄) 옥탄디브로마이드(참조화합물 I)과 1,10-비스-(4아미노-1-피리디늄) 테칸디브로마이드(참조화합물 II)의 대응 데이타도 비교 목적으로 표 A에 포함시켰다. 대표적인 화합물의 착색농도는 다음 표 C에 나타나 있다.Numerical data of antimicrobial, antifungal, and jig inhibition tests of these compounds are shown in Table A below. Two known compounds, namely 1,8-bis- (4-amino-1-pyridinium) octanedibromide (reference compound I) and 1,10-bis- (4 amino-1-pyridinium) tecandibromide ( Corresponding data of Reference Compound II) are also included in Table A for comparison purposes. Coloring concentrations of representative compounds are shown in Table C below.

대표적인 화합물들에 대한 혈청존재하의 항균효과를 표준 회석 계열법으로 측정하였으며, 이때 가열하여 불활성화한(30분, 56℃) 말의 혈청(40%)이 시험배지내에 존재하는 경우와 존재하지 않는 경우의 최소저지농도(MIC)를 비교 측정하였다. 이 측정의 결과는 혈청의 존재에 의해 스타필로코쿠스 아우레우스와 에쉘리히아 콜리의 최소 저지농도(mcg/ml)가 몇배로 증가하였는가 하는 것으로 표시되었으며, 이것은 다음 표 B에 나타나 있다.The antimicrobial effect of serum in the presence of representative compounds was measured by standard dilution series method, in which serum (40%) of horses inactivated by heating (30 minutes, 56 ° C) was present or not present in the test medium. The minimum Jersey concentration (MIC) of the cases was compared and measured. The results of this measurement indicate that the minimum stop concentration (mcg / ml) of Staphylococcus aureus and Escherichia coli increased by the presence of serum, which is shown in Table B below.

멸균시킨 사람의 타액(50%)의 존재하에서의 대표적인 화합물의 치구방지 효과를 측정하여 그 결과를 최소유효농도로 표시했으며, 이것은 다음 표 C에 나타나 있다.The antipruritic effect of a representative compound in the presence of saliva (50%) in sterile humans was measured and the results were expressed as minimum effective concentrations, which are shown in Table C below.

몇몇 대표적인 화합물의 급성 경구독성(ALD50)을 다음과 같이 측정했다. 즉, 성장한 숫컷 스위스-웹스터 균주 알미노 생쥐 3마리씩의 그룹을 약물투어 약 4시간 전부터 굶기고 위관(胃管)을 통해 경구적으로 한번 투여했다. 투약후 7일간 모든 생쥐를 관찰했다. 생쥐를 모두 해부한 결과, 실시예 25의 화합물 1000mg/kg을 투여한 그룹의 3마리중 2마리가 위선(胃腺)부분에 울혈이 관찰된 것을 제외하고는 어떤 육안적인 조직변화도 발견할 수 없었다. 그 결과가 다음 표 D에 나타나 있다.Acute oral toxicity (ALD 50 ) of several representative compounds was determined as follows. That is, a group of three grown male Swiss-Webster strain amino mice were starved for about 4 hours before the drug tour and administered orally once through the gastrointestinal tract. All mice were observed for 7 days after dosing. As a result of dissecting all the mice, no gross tissue change was found except that 2 out of 3 rats of 1000 mg / kg of the compound of Example 25 showed congestion in the gastric gland. . The results are shown in Table D below.

[표 A]TABLE A

Figure kpo00109
Figure kpo00109

Figure kpo00110
Figure kpo00110

Figure kpo00111
Figure kpo00111

Figure kpo00112
Figure kpo00112

Figure kpo00113
Figure kpo00113

Figure kpo00114
Figure kpo00114

[표 B]TABLE B

Figure kpo00115
Figure kpo00115

[표 C]TABLE C

Figure kpo00116
Figure kpo00116

※ 이 농도에서 어떤 박테리아 성장도 없었으며, 0.005%에서 치구가 형성됐다.※ There was no bacterial growth at this concentration, and jig was formed at 0.005%.

[표 D]TABLE D

Figure kpo00117
Figure kpo00117

Figure kpo00118
Figure kpo00118

Figure kpo00119
Figure kpo00119

Figure kpo00120
Figure kpo00120

* G.T. 트리가칸트 고무* G.T. Trigacanth rubber

Claims (1)

구조식(III)의 4-(R-아미노) 피리딘 2몰을 구조식(IV)의 이중 치환된 알칸 1몰 또는 구조식(V)의
Figure kpo00121
,
Figure kpo00122
'-이중치환 크실렌 1몰과 반응시킴을 특징으로 하는 구조식(I) 또는 구조식(II)의 비스-피리디늄 알칸의 제조방법.2 moles of 4- (R-amino) pyridine of formula (III) are substituted with 1 mole of double-substituted alkane of formula (IV) or
Figure kpo00121
,
Figure kpo00122
A process for preparing bis-pyridinium alkanes of formula (I) or (II), characterized in that it reacts with 1 mol of '-disubstituted xylene.
Figure kpo00123
Figure kpo00123
 상기 식에서In the above formula Y는 C4-C18의 알킬렌기로서, 두개의 4-(R-NH)-1-피리디닐기를 C4-C18에 의해 분리시키며; R은 C6~C18의 알킬기, C5-C7의 사이클로알킬기, 벤질이거나, 또는 할로겐, 저급 알킬, 저급 알콜시, 니트로, 시아노 또는 트리플루오로메틸 치환기 1-2개 또는 메틸렌 디옥시에 의해 치환된 페닐이다.Y is a C 4 -C 18 alkylene group that separates two 4- (R-NH) -1-pyridinyl groups by C 4 -C 18 ; R is a C 6 -C 18 alkyl group, a C 5 -C 7 cycloalkyl group, benzyl, or halogen, lower alkyl, lower alcohol, 1-2 nitro, cyano or trifluoromethyl substituents or methylene dioxy Phenyl substituted by
Figure kpo00124
Figure kpo00124
 상기 식에서 R은 수소, C1~C18의 직쇄 또는 측쇄 알킬기 A는 음이온;Wherein R is hydrogen, C 1 ~ C 18 linear or branched alkyl group A is an anion; 또는 벤질이며; m은 1 또는 3; Q는 메틸 또는 염소이고; n은 1 또는 2; V는 0-4의 정수이며; x는 1,2 또는 3이며;Or benzyl; m is 1 or 3; Q is methyl or chlorine; n is 1 or 2; V is an integer from 0-4; x is 1,2 or 3; 상기 구조식(I) 및 (II))에서; 이때(m) 2=(n)(x)이다.In the above formulas (I) and (II)); (M) 2 = (n) (x) at this time.
Figure kpo00125
Figure kpo00125
 상기 식에서In the above formula R은 구조식(I)의 화합물을 제조할 경우엔 구조식(I)의 R에 상응하며, 구조식(II)의 화합물을 제조할 경우엔 구조식(II)의 R에 상응한다.R corresponds to R in formula (I) when preparing a compound of formula (I), and R in formula (II) when preparing a compound of formula (II).
Figure kpo00126
Figure kpo00126
 상기 식에서In the above formula Z는 클로로, 브로모, 요오도, 메탄설포닐옥시, 에탄설포닐옥시, 벤젠설포닐옥시, 또는 P-톨루엔설포닐 옥시이며; 구조식(I) 및 (II)의 화합물에서 A는 Z에 상응하며;Z is chloro, bromo, iodo, methanesulfonyloxy, ethanesulfonyloxy, benzenesulfonyloxy, or P-toluenesulfonyl oxy; In the compounds of formulas (I) and (II) A corresponds to Z; Y, Q 및 V는 상술한 바와 같다.Y, Q and V are as described above.
KR7700427A 1977-02-24 1977-02-24 Process for preparing bis-pyridinium alkane KR810000932B1 (en)

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