JPS6399063A - Production of 4-amino-1,2,4-triazoline-5-thione compound - Google Patents
Production of 4-amino-1,2,4-triazoline-5-thione compoundInfo
- Publication number
- JPS6399063A JPS6399063A JP24312086A JP24312086A JPS6399063A JP S6399063 A JPS6399063 A JP S6399063A JP 24312086 A JP24312086 A JP 24312086A JP 24312086 A JP24312086 A JP 24312086A JP S6399063 A JPS6399063 A JP S6399063A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- group
- amino
- formula
- triazoline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 4-amino-1,2,4-triazoline-5-thione compound Chemical class 0.000 title claims description 27
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 239000012434 nucleophilic reagent Substances 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 24
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- 239000002904 solvent Substances 0.000 abstract description 7
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract description 6
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 abstract description 5
- LJTFFORYSFGNCT-UHFFFAOYSA-N Thiocarbohydrazide Chemical compound NNC(=S)NN LJTFFORYSFGNCT-UHFFFAOYSA-N 0.000 abstract description 4
- 239000000654 additive Substances 0.000 abstract description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical class OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 abstract description 3
- 230000002363 herbicidal effect Effects 0.000 abstract description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract description 2
- 230000002921 anti-spasmodic effect Effects 0.000 abstract description 2
- 239000000812 cholinergic antagonist Substances 0.000 abstract description 2
- 239000002934 diuretic Substances 0.000 abstract description 2
- 230000001882 diuretic effect Effects 0.000 abstract description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 abstract description 2
- BDAOOMQRIMJBNH-UHFFFAOYSA-N 1,4-dihydrotriazole-5-thione Chemical compound S=C1CN=NN1 BDAOOMQRIMJBNH-UHFFFAOYSA-N 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000013078 crystal Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000012038 nucleophile Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 150000001555 benzenes Chemical class 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 1
- ZMCQQCBOZIGNRV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-[2-(1,2,4-triazol-1-yl)ethyl]benzamide Chemical compound NCC1=CC(OC2=CC=CC(=C2)C(=O)NCCN2C=NC=N2)=NC(=C1)C(F)(F)F ZMCQQCBOZIGNRV-UHFFFAOYSA-N 0.000 description 1
- ZSWMSPXXQKJONO-UHFFFAOYSA-N 3-dodecylsulfonyl-2-methylpropanoyl chloride Chemical compound CCCCCCCCCCCCS(=O)(=O)CC(C)C(Cl)=O ZSWMSPXXQKJONO-UHFFFAOYSA-N 0.000 description 1
- VGPPNSOTEKQLED-UHFFFAOYSA-N 4-amino-3h-1,2,4-triazole-5-thione Chemical class NN1CN=NC1=S VGPPNSOTEKQLED-UHFFFAOYSA-N 0.000 description 1
- MHFRKHIBFYMILS-UHFFFAOYSA-N 4-hydrazinylphenol Chemical compound NNC1=CC=C(O)C=C1 MHFRKHIBFYMILS-UHFFFAOYSA-N 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000282373 Panthera pardus Species 0.000 description 1
- 241001061127 Thione Species 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- NOVHEGOWZNFVGT-UHFFFAOYSA-N hydrazine Chemical compound NN.NN NOVHEGOWZNFVGT-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- NSBIQPJIWUJBBX-UHFFFAOYSA-N n-methoxyaniline Chemical compound CONC1=CC=CC=C1 NSBIQPJIWUJBBX-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005064 octadecenyl group Chemical group C(=CCCCCCCCCCCCCCCCC)* 0.000 description 1
- IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- IYPZRUYMFDWKSS-UHFFFAOYSA-N piperazin-1-amine Chemical compound NN1CCNCC1 IYPZRUYMFDWKSS-UHFFFAOYSA-N 0.000 description 1
- KJAQRHMKLVGSCG-UHFFFAOYSA-N propan-2-ylhydrazine Chemical compound CC(C)NN KJAQRHMKLVGSCG-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は４−アミノ−１，２，４−トリアゾリン−５チ
オン系化合物の製造方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 4-amino-1,2,4-triazoline-5thione compounds.
４−アミノ−１，２，４−トリアゾリン−５−チオン系
化合物それ自体写真用添加剤として用いられるだけでな
く、各種化合物を製造するための中間体として用いられ
る。The 4-amino-1,2,4-triazoline-5-thione compound itself is used not only as a photographic additive, but also as an intermediate for producing various compounds.
写真用添加剤、例えば写真用カプラー（特にマゼンタカ
プラー）の中間体として有用な化合物である。It is a compound useful as an intermediate for photographic additives, such as photographic couplers (especially magenta couplers).
その他、４−アミノ−１，２，４−）−リアシン−５−
チオン系化合物はそれ自身抗菌作用、抗痙ψ作用、利尿
作用、除草作用をゆうしており、更に抗菌、除草などの
作用を有する化合物の中間体としても重要な化合物であ
る。Others, 4-amino-1,2,4-)-lyasin-5-
Thione compounds themselves have antibacterial, antispasmodic, diuretic, and herbicidal effects, and are also important compounds as intermediates for compounds having antibacterial and herbicidal effects.
［発明の背景コ
４−アミノ−１，２，４−）−リアゾリン−５−チオン
系化合物の合成に関しては、主に２つの方法が知られて
いる。[Background of the Invention] Two main methods are known for the synthesis of co-4-amino-1,2,4-)-riazoline-5-thione compounds.
第１の方法はへンス・バイヤー（）ｔａｎｓ Ｂｅｙｅ
ｒ）等によりアンナーレン・デア・ヘミ−、ラント。The first method is by Hens Beye
r) etc. by Annaren der Hemie, Land.
ファーマシ−（Ａｎｎ、）、６３７１ｋ１３Ｓ頁（１９
８０年）に報告されている方法であり、チオカルボヒド
ラジドと過剰の脂肪族カルボン酸または、脂肪族オルト
カルボン酸エステルを無溶媒中１００℃から１４０℃に
加熱し目的物を得ている。しかしこの方法は、反応試薬
である脂肪族カルボン酸または、脂肪族オルトカルボン
酸エステルを過剰に用いているため目的物との分離が困
難である。特に脂肪族カルボン酸または脂肪族オルトカ
ルボン酸エステルが常温で固体の場合その分離は一層困
難となり、収率が著しく低下する。さらに、反応温度が
高いことや、芳香族カルボン酸には適応が困難であるこ
と等、多くの欠点を有していた。Pharmacy (Ann, ), 6371k13S page (19
This is a method reported in 1980), in which thiocarbohydrazide and excess aliphatic carboxylic acid or aliphatic orthocarboxylic acid ester are heated from 100°C to 140°C in the absence of a solvent to obtain the desired product. However, this method uses an excessive amount of aliphatic carboxylic acid or aliphatic orthocarboxylic acid ester as a reaction reagent, making it difficult to separate it from the target product. In particular, when the aliphatic carboxylic acid or aliphatic orthocarboxylic acid ester is solid at room temperature, its separation becomes even more difficult and the yield significantly decreases. Furthermore, it had many drawbacks, such as high reaction temperature and difficulty in adapting to aromatic carboxylic acids.
第２の方法は、エリツク・ホーガス（Ｅｒｌｃ ）ｌｏ
ｇｇａｒｔｈ）によりジャーナル・オン・ザ・ケミカル
・ソサイアテイ（Ｊ、Ｃｈｅｎ、Ｓｏｃ、）、１！１５
２年、４８１１頁に報告されている方法であり、カルボ
ンサン誘導体とヒドラジンとの反応で得られるヒドラジ
ド説導体に二硫化炭素、次いで沃化メチルを反応させ更
にヒドラジンを反応させることにより目的物を得ている
。この方法は、芳香族カルボン酸説導体にも適応可能で
あり、反応温度も１００℃以下と低く、優れた方法であ
るが、反応工程が長いうえに収率が低いという大きな欠
点を有していた。The second method is by Eric Hogus (Erlc) lo
Journal on the Chemical Society (J, Chen, Soc,), 1!15
2, p. 4811, in which the desired product is obtained by reacting a hydrazide conductor obtained by the reaction of a carboxane derivative with hydrazine, carbon disulfide, then methyl iodide, and further reacting with hydrazine. It has gained. Although this method is applicable to aromatic carboxylic acid conductors and has a low reaction temperature of 100°C or less, it is an excellent method, but it has major drawbacks such as long reaction steps and low yields. Ta.
その他、西海技束雄等により薬学雑誌、８２巻、６８３
頁（１９６２年）に報告されている２−クロロ−１，３
，４−チアジアゾール誘導体とヒドラジンを反応させる
方法や、ケミカル、アブストラクトト７６巻、 １４０
７４１１１（１９７２年）に報告されている１、３．４
−オキサジアゾール−２−チオン誘導体とヒドラジンを
反応させる方法が知られているが、満足する結果は得ら
れなかった。Others, by Takao Nishikai et al., Pharmaceutical Journal, vol. 82, 683.
2-chloro-1,3 reported in p. (1962)
, Method of Reacting 4-Thiadiazole Derivatives with Hydrazine, Chemical Abstracts Volume 76, 140
1, 3.4 reported in 74111 (1972)
A method of reacting an -oxadiazole-2-thione derivative with hydrazine is known, but no satisfactory results were obtained.
本発明者等は、従来法の４−アミノ−１，２゜４−トリ
アゾン−５−チオン系化合物の製造方法が収率が低いば
かりでなく、工程も複雑であるなどの欠点を有している
点に鑑み、簡単に合成することができ、しかも高収率の
得られる合成方法を探求する中で、本発明を完成するに
至ったものである。The present inventors have discovered that the conventional method for producing 4-amino-1,2゜4-triazone-5-thione compounds has drawbacks such as low yield and complicated steps. In view of the above, the present invention was completed while searching for a synthetic method that can be easily synthesized and provide a high yield.
［発明の目的］
したがって、本発明の目的は、前記欠点を解決すること
にあり、その第１の目的は、反応工程が短く、しかも低
い反応温度で反応して、高収率の得られる４−アミノ−
１，２，４−）リアシリ、シーＳ−チオン系化合物の製
造方法を提供することにある。[Objective of the Invention] Therefore, the object of the present invention is to solve the above-mentioned drawbacks, and the first object is to obtain a high-yield 4. -Amino-
An object of the present invention is to provide a method for producing a 1,2,4-)riasili, cy-S-thione compound.
第２の目的は、脂肪族または芳香族のいずれのカルボン
酸誘導体とも容易に反応しつる分子構造的な適応範囲の
広い４−アミノ−１，２，４−トリアゾリン−５−チオ
ン系化合物の製造方法を提供することにある。The second objective is to produce a 4-amino-1,2,4-triazoline-5-thione compound that easily reacts with either aliphatic or aromatic carboxylic acid derivatives and has a wide range of molecular structure adaptability. The purpose is to provide a method.
［発明の構成］
本発明の前記目的は、一般式［Ｉ］で示される化合物に
求核試薬を反応させることにより、−ａ式［Ｉ■］で示
される４−アミノ−１，２，４−トリアゾリン−５−チ
オン系化合物を製造する方法により達成された。[Structure of the Invention] The object of the present invention is to produce 4-amino-1,2,4 represented by the -a formula [I■] by reacting the compound represented by the general formula [I] with a nucleophilic reagent. This was achieved by a method for producing -triazoline-5-thione compounds.
一般式［！］
一般式［■！］
［式中、Ｆｔ、 、 Ｒ２およびＲ５は各々、水素原子
、アルキル基、アルケニル基、シクロアルキル基、アリ
ール基または複素環基を表わす、］一般式［Ｉ１のＲ１
、Ｒ２およびＲ５は具体的には、水素原子、直鎮又は分
枝のアルキル基（例えばメチル、エチル、イソプロピル
、ブチル、ｔ−ブチル、オクチル、ペンタデシル、エイ
コシル等の各基）、アルケニル基（例えばビニル、プロ
ペニル、ブテニル、ヘキセニル、ペンタデセニル、オク
タデセニル等の各基）、シクロアルキル基（例えばシク
ロペンチル基、シクロヘキシル基）、アリール基（例え
ばフェニル基、ナフチル基）および複素環基（例えばピ
リジル、フリル、チェニル等の各基）を挙げることがで
きる。これらアルキル基、アルケニル基、アリール基お
よび複素環基は置換基を有することができ、置換基とし
てはハロゲン原子、ヒドロキシル基、ニトロ基、シアノ
基、アルキル基、アルコキシ基、アリールオキシ基、ア
ルキルスルホニル基、アリールスルホニル基、アシルオ
キシ基、アシルアミノ基、カルバモイル基、スルホンア
ミド基、スルファモイル基等を挙げることができる。更
に置換基中のアルキル鎖は直鎮または分枝のものを用い
ることができる。ＲＩとしてはアルキル基またはアリー
ル基が好ましいｅＲ２およびＲ８としては、Ｒ３が水素
原子の場合、Ｒ８はアリール基または複素環基が好まし
く、Ｒ６がアルキル基の場合、Ｒ１はアルキル基または
アリール基が好ましい。General formula [! ] General formula [■! ] [In the formula, Ft, , R2 and R5 each represent a hydrogen atom, an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group or a heterocyclic group] General formula [R1 of I1
, R2 and R5 are specifically hydrogen atoms, straight or branched alkyl groups (e.g. methyl, ethyl, isopropyl, butyl, t-butyl, octyl, pentadecyl, eicosyl, etc.), alkenyl groups (e.g. vinyl, propenyl, butenyl, hexenyl, pentadecenyl, octadecenyl, etc.), cycloalkyl groups (e.g. cyclopentyl group, cyclohexyl group), aryl groups (e.g. phenyl group, naphthyl group), and heterocyclic groups (e.g. pyridyl, furyl, chenyl group). etc.) can be mentioned. These alkyl groups, alkenyl groups, aryl groups, and heterocyclic groups can have substituents, and substituents include halogen atoms, hydroxyl groups, nitro groups, cyano groups, alkyl groups, alkoxy groups, aryloxy groups, and alkylsulfonyl groups. group, arylsulfonyl group, acyloxy group, acylamino group, carbamoyl group, sulfonamide group, sulfamoyl group and the like. Further, the alkyl chain in the substituent may be straight or branched. RI is preferably an alkyl group or an aryl group eR2 and R8, when R3 is a hydrogen atom, R8 is preferably an aryl group or a heterocyclic group, and when R6 is an alkyl group, R1 is preferably an alkyl group or an aryl group. .
また、Ｒ３およびＲ４が共にアルキル基の場合、結合、
して５〜７員炭化水素環を形成してもよい。In addition, when R3 and R4 are both alkyl groups, a bond,
may be used to form a 5- to 7-membered hydrocarbon ring.
Ｒ２またはＲ３がアリール基の場合の置換基としては、
アルキル基（例えばメチル基、エチル基等）、ヒドロキ
シル基、ニトロ基およびハロゲン原子が好ましい、一般
式［Ｉ１で示される化合物は下記スキームエのようにチ
オカルボヒドラジドより容易に合成される。As substituents when R2 or R3 is an aryl group,
Alkyl groups (for example, methyl groups, ethyl groups, etc.), hydroxyl groups, nitro groups, and halogen atoms are preferred, and the compound represented by the general formula [I1] can be easily synthesized from thiocarbohydrazide as shown in Scheme E below.
スキームＩ
また合成物（３）は化合物（１）とアセタール化合物と
の反応によっても合成される。Scheme I Compound (3) can also be synthesized by reacting compound (1) with an acetal compound.
次に本発明で用いられる一般式［Ｉ］で示される化合物
の代表的具体例を以下に示すが本発明はこれらに限定さ
れない。Next, typical examples of the compound represented by the general formula [I] used in the present invention are shown below, but the present invention is not limited thereto.
一般式［Ｉ］で示される化合物
本発明で用いられる求核試薬の例としては非具有有子対
を有するもので、好ましくは水酸イオン、アルコキシア
ニオン、アリールオキシアニオン、アミノ基、ヒドラジ
ノ基を有する化合物を挙げることができる。Compounds represented by general formula [I] Examples of nucleophilic reagents used in the present invention include those having a non-concrete pair, preferably a hydroxyl ion, an alkoxy anion, an aryloxy anion, an amino group, or a hydrazino group. Examples include compounds that have
アルコキシアニオンとしてはメトキシアニオン、エトキ
シアニオン等があり、またアリールオキシアニオンとし
てはフェノキシアニオン、クロロフェノキシアニオン等
が、さらにアミノ基を有する化合物としてはヒドロキシ
ルアミン、０−メチルヒドロキシルアミン、０−エチル
ヒドロキシルアミン、メチルアミン、ジメチルアミン、
エチルアミン、ジエチルアミン、プロピルアミン、オク
チルアミン、アニリン、メトキシアニリン、アミノフェ
ノール、メチルアニリン等、ヒドラジノ基を有する化合
物の例としては、ヒドラジンヒトラード、ジメチルヒド
ラジン、１−アミノピペラジン、フェニルヒドラジン、
ｐ−ヒドラジノフェノール、イソプロピルヒドラジン等
をそれぞれ挙げることができる。これらの求核試薬のう
ち、ヒドロキシルアミンまたは、ヒドラジンヒトラード
が特に好ましい、これら求核試薬は一般式［！］で示さ
れる化合物１モルに対して１〜１００モル、好ましくは
１〜１０モルが用いられる。Alkoxy anions include methoxy anions and ethoxy anions, aryloxy anions include phenoxy anions and chlorophenoxy anions, and compounds with amino groups include hydroxylamine, 0-methylhydroxylamine, and 0-ethylhydroxylamine. , methylamine, dimethylamine,
Examples of compounds having a hydrazino group such as ethylamine, diethylamine, propylamine, octylamine, aniline, methoxyaniline, aminophenol, and methylaniline include hydrazine hydrazine, dimethylhydrazine, 1-aminopiperazine, phenylhydrazine,
Examples include p-hydrazinophenol and isopropylhydrazine. Among these nucleophiles, hydroxylamine or hydrazine hittride is particularly preferred; these nucleophiles have the general formula [! ] is used in an amount of 1 to 100 mol, preferably 1 to 10 mol, per mol of the compound represented by.
一般式［Ｉ１で示される化合物と求核試薬の反応は溶媒
中で行われる。該溶媒としては、ケトン類やアルデヒド
類の如くカルボニル基や酢酸エチルエステルの如くエス
テル結合を有しない化合物、例えばアルコール類、ベン
ゼン類、エーテル類、ハロゲン化炭化水素、アミド類等
を代表的に挙げることができる。このうち、好ましいも
のとしてはアルコール類、エーテル類およびアミド類で
でり、特に好ましいものはアルコール類である。この他
溶媒は、求核試薬または生成物と反応を起さないもので
あれば、特に制限されない。The reaction between the compound represented by the general formula [I1 and the nucleophile] is carried out in a solvent. Typical examples of the solvent include compounds that do not have carbonyl groups such as ketones and aldehydes and ester bonds such as ethyl acetate, such as alcohols, benzenes, ethers, halogenated hydrocarbons, and amides. be able to. Among these, alcohols, ethers and amides are preferred, and alcohols are particularly preferred. Other solvents are not particularly limited as long as they do not react with the nucleophile or the product.
本発明において用いられるアルコール類としては、例え
ばメタノール、エタノール、ｎ−プロパツール、エチレ
ングリコール、エチレングリコールモノメチルエーテル
等を挙げることができる。Examples of alcohols used in the present invention include methanol, ethanol, n-propanol, ethylene glycol, and ethylene glycol monomethyl ether.
また、ベンゼン類としては、ベンゼン、ニトロベンゼン
、トルエン、キシレン等が挙げられる。さらにエーテル
類としてはジエチルエーテル、エチレングリコールジメ
チルエーテル、ジエチレンゲルコールジメチルエーテル
、テトラヒドロフラン、ジオキサン等が挙げられる。ハ
ロゲン化炭化水素としては、四塩化炭素、クロロホルム
、ブロモホルム等を挙げることができ、アミド類として
はホルムアミド、 Ｎ、Ｎ−ジメチルホルムアミド等が
挙げられる。Furthermore, examples of benzenes include benzene, nitrobenzene, toluene, xylene, and the like. Furthermore, examples of ethers include diethyl ether, ethylene glycol dimethyl ether, diethylene gelcol dimethyl ether, tetrahydrofuran, and dioxane. Examples of halogenated hydrocarbons include carbon tetrachloride, chloroform, and bromoform, and examples of amides include formamide, N,N-dimethylformamide, and the like.
これら溶媒において、水と混和するアルコール類、エー
テル類およびアミド類は水との混合溶媒比もよい、溶媒
は一般式［Ｉ１の化合物１重量部当り１〜５０重量部、
好ましくは２〜１Ｏ５ｉ量部の割合で用いられる。In these solvents, alcohols, ethers, and amides that are miscible with water have a good mixed solvent ratio with water, and the solvent is 1 to 50 parts by weight per 1 part by weight of the compound of the general formula
It is preferably used in a proportion of 2 to 1 O5i parts.
反応温度は０〜ｔＳＯ℃が好ましく、特に４０〜１００
℃が好ましい０反応に要する時間は特に限定されないが
、好ましくは５分〜２０時間、より好ましくは１時間〜
１０時間である。上記記載の如き本発明の方法によれば
一般式［■！］で示される４−アミノ−１，２，４−ト
リアゾリン−５−チオン系化合物が高収率で得られる。The reaction temperature is preferably 0 to tSO°C, particularly 40 to 100°C.
The time required for the reaction is not particularly limited, but is preferably 5 minutes to 20 hours, more preferably 1 hour to 20 hours.
It is 10 hours. According to the method of the present invention as described above, the general formula [■! A 4-amino-1,2,4-triazoline-5-thione compound represented by the following formula can be obtained in high yield.
次に一般式［ＩＩ ］で示される化合物の代表的具体例
を以下に示すが本発明は、これらに限定されない。Next, typical examples of the compound represented by the general formula [II] are shown below, but the present invention is not limited thereto.
４−アミノ−１，２，４−トリアゾリン系化合物は下記
のような互変異性体［Ａ］および［Ｂ］が考えられが、
具体例ではチオカルボニル基［Ａ］として示す。The 4-amino-1,2,4-triazoline compound may have the following tautomers [A] and [B],
In a specific example, it is shown as a thiocarbonyl group [A].
［Ａ］ ［Ｂ］■ −１
ｍ−２
Ｉ−３
Ｉ−７
ｆ−８
ｌ−１３
１！−１４
■ −２０
■ −２１
■ −２４
Ｉ−２８
ｌｔ−２７
ｕ−Ｌ＋＠Ｉｌｌす
亘−３９
１［−４２
ｌ−４３
π −４６
Ｎ −Ｎ Ｈ
［実施例］
以下に本発明の具体的実施例を記載するが、本発明はこ
れに限定されない。[A] [B] ■ -1 m-2 I-3 I-7 f-8 l-13 1! -14 ■ -20 ■ -21 ■ -24 I-28 lt-27 u-L+@Illsuwa-39 1 [-42 l-43 π -46 N -NH [Example] The following is a specific example of the present invention. Although a typical example will be described, the present invention is not limited thereto.
実施例１
４−アミノ−３−フェニル−トリアゾリン−５−チオン
（例示化合物１１−９ ）
１−ペンジリデンーチオカルボノヒドラジン１９．４ｇ
とトリエチルアミン１２．０ｇをアセトニトリル２０１
）ａ４に加え加熱還流下ベンゾイルクロライド１５．４
ｇを１０分間で滴下した６滴下後３０分間加熱還流した
後冷却した。析出した結晶を濾過し、水洗し化合物例１
−９を得た。この結晶を未乾燥のまま、エタノール３０
０ａｌＩｔに加えた。さらに５０零ヒドロキシルアミン
水溶液２０．０ｇを加え５時間加熱還流した後、エタノ
ールを減圧下留去した。残渣をアルコール−水から再結
晶し、無色、針状結晶の例示化合物！■−９を得た。収
量１０．２ｇ（収率５３ｔ）融点２０３〜２０４℃、Ｆ
Ｄ−マススペクトルが１９２を示しＩＲ，ＮＭＲも上記
構造を支持した。Example 1 4-Amino-3-phenyl-triazoline-5-thione (Exemplary Compound 11-9) 1-penzylidene-thiocarbonohydrazine 19.4 g
and 12.0 g of triethylamine in 201 g of acetonitrile.
) a4 plus benzoyl chloride under heating reflux 15.4
After adding 6 drops of g over 10 minutes, the mixture was heated under reflux for 30 minutes and then cooled. The precipitated crystals were filtered and washed with water to form Compound Example 1.
-9 was obtained. Leave the crystals undried and add 30 ml of ethanol.
Added to 0alIt. Further, 20.0 g of a 50-hydroxylamine aqueous solution was added and heated under reflux for 5 hours, and then ethanol was distilled off under reduced pressure. The residue was recrystallized from alcohol-water to give an example compound of colorless, needle-shaped crystals! ■-9 was obtained. Yield 10.2g (yield 53t) Melting point 203-204℃, F
The D-mass spectrum showed 192, and IR and NMR also supported the above structure.
元素分析値（Ｃａ Ｈａ Ｎ４ Ｓ）
計算値（％） Ｃ：４９．９８ Ｈ：４．１９ Ｎ：２
９．１４ Ｓ：１６．６８実測値（％） Ｃ：５Ｇ、２
１ Ｈ：４．０７ Ｎ：２９．３８ Ｓ：１８．２９実
施例２
４−アミノ−３−ペンタデシル−トリアゾリン−５−チ
オン
（例示化合物ｌｌ−７）
１−ペンジリデンーチオヵルボノヒドラジン１９．４ｇ
とビリジ）’１０．０ｇをアセトニトリル２００ｍｕｋ
：加え加熱還流下バルミチン酸クロライド２７．５ｇを
５０分間で滴下した。さらに３０分間還流した後、冷却
し、析出している結晶を濾過し、アセトニトリルで洗浄
した後水洗し、乾燥した。白色の例示化合物１−７．３
６．６ｇ（収率８５豹を得た。Elemental analysis value (Ca Ha N4 S) Calculated value (%) C: 49.98 H: 4.19 N: 2
9.14 S: 16.68 Actual value (%) C: 5G, 2
1 H: 4.07 N: 29.38 S: 18.29 Example 2 4-amino-3-pentadecyl-triazoline-5-thione (exemplified compound 11-7) 1-penzylidene-thiocarbonohydrazine 19 .4g
and viridi)'10.0g to 200muk of acetonitrile
:Additionally, 27.5 g of valmitic acid chloride was added dropwise over 50 minutes while heating under reflux. After refluxing for an additional 30 minutes, the mixture was cooled, and precipitated crystals were filtered, washed with acetonitrile, water, and dried. White exemplary compound 1-7.3
6.6 g (yield 85 leopard) was obtained.
融点１６５〜１６７℃
上記、例示化合物Ｉ−７３０，３３とＳＯｔヒドロキシ
ルアミン水溶液（ＦＨ−５ｏ、日進化工株式会社製）
１１．６ｇ ヲエタ／ −ｋ ３００ｍ１ｌ ニ加え５
時間加熱還流した６反応液を冷却し析出した結晶を濾過
し、エタノールで洗浄後、乾燥し、白色粉末状結晶の例
示化合物！！−７を得た。収量１９．２ｇ（収率８４９
６）、融点１２１〜１２３℃、ＦＤマススペクトルが３
２６を示し、ＩＲ，ＮＭＲも上記構造を支持した。Melting point: 165-167°C Exemplary compound I-730,33 and SOt hydroxylamine aqueous solution (FH-5o, manufactured by Nichika Kogyo Co., Ltd.)
11.6g weta/-k 300ml 1L 5
6 The reaction solution was heated under reflux for an hour and then cooled, the precipitated crystals were filtered, washed with ethanol, and dried to give an exemplary compound as white powder crystals! ! -7 was obtained. Yield 19.2g (yield 849
6), melting point 121-123℃, FD mass spectrum 3
26, and IR and NMR also supported the above structure.
元素分析値（ＣＩ？Ｈ３７Ｎ４ Ｓ）
計算値（％） Ｃ：６２．５２ Ｈ：１０．５０ Ｎ：
１７．１６ Ｓ：９．８２実測値（％） Ｃ：８２．３
８ Ｈ：１０．３６ Ｎ：１７．２５ Ｓ：１０．１１
実施例３
４−アミノ−３−（α−メチル−β−ドデシルスルホニ
ルエチル）−トリアゾリン−５−チオン（例示化合物ｌ
ｌ−２０）（その１）
１−ペンジリデンーチオヵルボノヒドラジン２３．０ｇ
とピリジン１１．０ｇをアセトニトリル３００ｍＪ２に
加え６０〜６５℃に加熱した０次いで、α−メチル−β
−ドデシルスルホニルプロピオン酸クロライド４０．０
ｇをアセトニトリル１００ｎｌに溶解した溶液を１０分
間で滴下した０滴下後３０分間加熱還流し、放冷した。Elemental analysis value (CI?H37N4 S) Calculated value (%) C: 62.52 H: 10.50 N:
17.16 S: 9.82 Actual value (%) C: 82.3
8 H:10.36 N:17.25 S:10.11
Example 3 4-Amino-3-(α-methyl-β-dodecylsulfonylethyl)-triazoline-5-thione (Exemplary Compound l
l-20) (Part 1) 1-penzylidene-thiocarbonohydrazine 23.0g
and 11.0 g of pyridine were added to 300 mJ2 of acetonitrile and heated to 60-65°C. Then, α-methyl-β
-Dodecylsulfonylpropionic acid chloride 40.0
A solution prepared by dissolving G in 100 nl of acetonitrile was added dropwise over 10 minutes. After the dropwise addition, the mixture was heated under reflux for 30 minutes and allowed to cool.
析出した結晶を濾過し、アセトニトリルで洗浄した後水
洗し、乾燥した。淡かっ色の例示化合物！−２０を３７
．８ｇ（収率８２豹を得た。融点１３２〜１３５ ℃
上記、例示化合物１−２０を２８．０ｇと５０％ヒドロ
キシルアミン水溶液９．９をエタノール２１０ｍｌ１に
加え、６時間加熱還流した。反応液を冷却し、析出した
結晶を濾過し、エタノールで洗浄後、乾燥し、白色粉末
状結晶の例示化合物ｌｌ−２０を得た。The precipitated crystals were filtered, washed with acetonitrile, water, and dried. Pale brown exemplified compound! -20 to 37
．． 8 g (yield: 82 yam) was obtained. Melting point: 132-135° C. 28.0 g of Exemplified Compound 1-20 and 9.9 g of a 50% hydroxylamine aqueous solution were added to 210 ml of ethanol, and the mixture was heated under reflux for 6 hours. After cooling, the precipitated crystals were filtered, washed with ethanol, and then dried to obtain Exemplary Compound 11-20 as white powdery crystals.
収量１５．６ｇ（収率７１９６）融点１１１〜１１３℃
ＦＤマススペクトルが３９０を示し、ＩＲ，ＮＭＲも上
記構造を支持した。Yield 15.6g (yield 7196) Melting point 111-113℃
The FD mass spectrum showed 390, and IR and NMR also supported the above structure.
元素分析値（Ｃ＋ｔＨｓａＮ４０２ Ｓ２ ）計算値（
％） Ｃ：５２．２８ Ｈ：８．７７ Ｎ：１４．３
４ Ｓ：１６．４２実測値（％）Ｃ：５２．１６ Ｈ：
８．７３ Ｎ：１４．５２ Ｓ：１６．６Ｂ実施例４
４−アミノ−３−（α−メチル−β−ドデシルスルホニ
ルエチル）−トリアゾリン−５−チオン（例示化合物ｌ
ｌ−２０）（その２）
実施例３で合成した例示化合物ｌ−２０１４，０ｇと８
００４抱水ヒドラジン８．８ｇを１００＋ｌのエタノー
ルに加え４時間加熱還流した。反応液を冷却し、析出し
た結晶を濾過し、エタノールで洗浄後、乾燥し、白色粉
末状結晶の例示化合物１１−２０を得た。Elemental analysis value (C+tHsaN402 S2) Calculated value (
%) C: 52.28 H: 8.77 N: 14.3
4 S: 16.42 Actual value (%) C: 52.16 H:
8.73 N: 14.52 S: 16.6B Example 4 4-Amino-3-(α-methyl-β-dodecylsulfonylethyl)-triazoline-5-thione (Exemplary Compound l
l-20) (Part 2) Exemplary compounds l-2014, 0g and 8 synthesized in Example 3
004 hydrazine hydrate (8.8 g) was added to 100+ liters of ethanol and heated under reflux for 4 hours. The reaction solution was cooled, and the precipitated crystals were filtered, washed with ethanol, and dried to obtain Exemplary Compound 11-20 as white powdery crystals.
収量７．２ｇ（収率６５９６）融点１１０〜１１２℃。Yield 7.2g (yield 6596) Melting point 110-112°C.
ＩＲおよびＮＭＲは、実施例３で得た例示化合物Ｉ＋−
２０と完全に一致した。IR and NMR are for the exemplified compound I+- obtained in Example 3.
It matched perfectly with 20.
実施例５
４−アミノ−３−（２，４−ジクロルフェノキシメチル
）−トリアゾリン−５−チオン（例示化合物ｌｌ−１４
）
１−（２−フルフリリデン）−チオカルボッヒドラジン
１８．４ｇとピリジン１０．０ｇを酢酸エチルに加え、
室温下２．４−ジクロルフェノキシ酢酸クロライド２０
．４ｇを３０分間で滴下した。さらに３時間攪拌した後
、酢酸エチル層を水洗し、減圧下酢酸エチルを留去し淡
かっ色の例示化合物ｌ−１４を得た。Example 5 4-amino-3-(2,4-dichlorophenoxymethyl)-triazoline-5-thione (exemplified compound ll-14
) Add 18.4 g of 1-(2-furfurylidene)-thiocarbohydrazine and 10.0 g of pyridine to ethyl acetate,
2.4-dichlorophenoxyacetic acid chloride 20 at room temperature
．． 4 g was added dropwise over 30 minutes. After further stirring for 3 hours, the ethyl acetate layer was washed with water, and the ethyl acetate was distilled off under reduced pressure to obtain a pale brown exemplified compound 1-14.
未精製のまま上記例示化合物■−１４にエタノール２０
０ｏ＋１および５０零ヒドロキシルアミン水溶液２０．
０ｇを加え、５時間加熱還流した。放冷後析出した結晶
を濾過し、エタノールで洗浄後、乾燥し、白色針状結晶
の例示化合物１１−１４を得た。Add 20% ethanol to the above exemplified compound ■-14 without purification.
0o+1 and 50 zero hydroxylamine aqueous solutions 20.
0 g was added, and the mixture was heated under reflux for 5 hours. After cooling, the precipitated crystals were filtered, washed with ethanol, and dried to obtain Exemplified Compound 11-14 as white needle-like crystals.
収量１３．２ｇ、（収率４８零）、融点１８３〜１８５
℃。Yield 13.2g, (yield 480), melting point 183-185
℃.
ＦＤ−マススペクトルが２７５を示しＩＲ，ＮＭＲも上
記構造を支持した。The FD-mass spectrum showed 275, and the IR and NMR also supported the above structure.
元素分析値（Ｃｓ Ｈａ Ｎ４ Ｃｆ１２Ｓ）計算値（
％） Ｃ：３９．２９ Ｈ：２．９３ Ｎ：２０
．３６実測値（％） Ｃ：３９．５０ Ｈ：２．７８
Ｎ：２０．１５比較例−１（従来法）
４−アミノ−３−（α−メチル−β−ドデシルスルホニ
ルエチル）−トリアゾリン−５−チオン（例示化合物ｌ
ｌ−２０）
チオカルボヒドラジド５．３ｇとα−メチル−β−ドデ
シルスルホニルエチルプロビオン酸４１．６ｇを混合し
、１３５〜１４０℃で１時間反応させた。反応後冷却し
、固化した固体をエタノールから再結晶した。析出した
結晶にはα−メチル−β−ドデシルスルホニルエチルプ
ロピオン酸が含まれていたのでさらに再結晶を繰り返し
、白色粉末状の例示化合物ｌｌ−２０を得た。収量２．
３ｇ（収率１２１１゜融点１０８〜１１１℃、ＩＲおよ
びＮＭＲは実施例３で得た例示化合物ｌｌ−２０と一致
した。Elemental analysis value (Cs Ha N4 Cf12S) calculated value (
%) C: 39.29 H: 2.93 N: 20
．． 36 Actual value (%) C: 39.50 H: 2.78
N: 20.15 Comparative Example-1 (Conventional method) 4-Amino-3-(α-methyl-β-dodecylsulfonylethyl)-triazoline-5-thione (Exemplary Compound l
l-20) 5.3 g of thiocarbohydrazide and 41.6 g of α-methyl-β-dodecylsulfonylethylprobionic acid were mixed and reacted at 135 to 140°C for 1 hour. After the reaction was cooled, the solidified solid was recrystallized from ethanol. Since the precipitated crystals contained α-methyl-β-dodecylsulfonylethylpropionic acid, recrystallization was repeated to obtain exemplified compound 11-20 in the form of a white powder. Yield 2.
3 g (yield: 1211°, melting point: 108-111°C, IR and NMR were consistent with exemplified compound 11-20 obtained in Example 3).
［発明の効果］
実施例からも分かるように、本発明の４−アミノ−１，
２，４−１−リアゾリン−５−チオン系化合物の製造方
法は、置換基の適応範囲が広く、高収率で目的物が得ら
れる優れた方法であり、さらに反応工程が短いうえ、反
応温度も低く、上記化合物の製造方法として十分満足す
る結果を得ることができる。[Effect of the invention] As can be seen from the examples, the 4-amino-1,
The method for producing 2,4-1-riazoline-5-thione compounds is an excellent method that can be applied to a wide range of substituents and provides the desired product in high yield.In addition, the reaction process is short and the reaction temperature is low. It is possible to obtain sufficiently satisfactory results as a method for producing the above-mentioned compound.
以上that's all
Claims (1)
させることを特徴とする、一般式［II］で示される４−
アミノ−１，２，４−トリアゾリン−５−チオン系化合
物の製造方法。 一般式［ I ］ ▲数式、化学式、表等があります▼ 一般式［II］ ▲数式、化学式、表等があります▼ ［式中、Ｒ＿１、Ｒ＿２およびＲ＿３は各々、水素原子
、アルキル基、アルケニル基、シクロアルキル基、アリ
ール基、または複素環基を表わす。］[Scope of Claims] A 4- compound represented by the general formula [II], characterized in that the compound represented by the general formula [I] and a nucleophilic reagent are reacted.
A method for producing an amino-1,2,4-triazoline-5-thione compound. General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ General formula [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, R_1, R_2, and R_3 are each a hydrogen atom, an alkyl group, or an alkenyl group. , represents a cycloalkyl group, an aryl group, or a heterocyclic group. ]
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24312086A JPH0672142B2 (en) | 1986-10-15 | 1986-10-15 | Method for producing 4-amino-1,2,4-triazoline-5-thione compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP24312086A JPH0672142B2 (en) | 1986-10-15 | 1986-10-15 | Method for producing 4-amino-1,2,4-triazoline-5-thione compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6399063A true JPS6399063A (en) | 1988-04-30 |
| JPH0672142B2 JPH0672142B2 (en) | 1994-09-14 |
Family
ID=17099096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP24312086A Expired - Lifetime JPH0672142B2 (en) | 1986-10-15 | 1986-10-15 | Method for producing 4-amino-1,2,4-triazoline-5-thione compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0672142B2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996001812A1 (en) * | 1994-07-07 | 1996-01-25 | Merrell Pharmaceuticals Inc. | Process for the preparation of 5-aryl-2,4-dialkyl-3h-1,2,4-triazole-3-thiones |
| EP3934639A4 (en) * | 2019-03-04 | 2023-01-11 | Epitracker, Inc. | Fatty acid analogs and their use in the treatment of cognitive impairment, behavioral conditions, and chronic pain |
| US11951088B2 (en) | 2017-10-23 | 2024-04-09 | Epitracker, Inc. | Fatty acid analogs and their use in the treatment of conditions related to metabolic syndrome |
-
1986
- 1986-10-15 JP JP24312086A patent/JPH0672142B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996001812A1 (en) * | 1994-07-07 | 1996-01-25 | Merrell Pharmaceuticals Inc. | Process for the preparation of 5-aryl-2,4-dialkyl-3h-1,2,4-triazole-3-thiones |
| US11951088B2 (en) | 2017-10-23 | 2024-04-09 | Epitracker, Inc. | Fatty acid analogs and their use in the treatment of conditions related to metabolic syndrome |
| EP3934639A4 (en) * | 2019-03-04 | 2023-01-11 | Epitracker, Inc. | Fatty acid analogs and their use in the treatment of cognitive impairment, behavioral conditions, and chronic pain |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0672142B2 (en) | 1994-09-14 |
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