KR101132427B1 - New reaction solvent and preparation thereof - Google Patents

New reaction solvent and preparation thereof Download PDF

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KR101132427B1
KR101132427B1 KR1020090120189A KR20090120189A KR101132427B1 KR 101132427 B1 KR101132427 B1 KR 101132427B1 KR 1020090120189 A KR1020090120189 A KR 1020090120189A KR 20090120189 A KR20090120189 A KR 20090120189A KR 101132427 B1 KR101132427 B1 KR 101132427B1
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유재상
정윤경
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이화여자대학교 산학협력단
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    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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Abstract

본 발명은 반응용매로서의 하기 화학식 1의 이온성 액체를 제공한다:The present invention provides an ionic liquid of formula 1 as a reaction solvent:

[화학식 1][Formula 1]

Figure 112009075196023-pat00001
Figure 112009075196023-pat00001

상기식에서, R1 및 R2는 각각 C1-C4의 알킬기 또는 벤질기를 나타내며, X는 I(iodide), NTf2(bis((trifluoromethyl)sulfonyl)amide), OTf(trifluoromethylsulfonate), PF6(hexafluorophosphate) 또는 BF4(tetrafluoroborate) 이다.Wherein R 1 and R 2 each represent an alkyl group or benzyl group of C 1 -C 4 , X represents I (iodide), NTf 2 (bis ((trifluoromethyl) sulfonyl) amide), OTf (trifluoromethylsulfonate), PF 6 ( hexafluorophosphate) or BF 4 (tetrafluoroborate).

이온성 액체, 1,3-디알킬-1,2,3-트리아졸륨, Baylis-Hillman 반응 Ionic Liquid, 1,3-Dialkyl-1,2,3-triazolum, Baylis-Hillman Reaction

Description

신규한 반응용매 및 이의 제조방법{New reaction solvent and preparation thereof} New reaction solvent and preparation method thereof

본 발명은 신규한 반응용매 및 이의 제조방법에 관한 것이다.The present invention relates to a novel reaction solvent and a preparation method thereof.

이온성 액체는 100 ℃ 이하에서 녹는 유기 염으로 정의되며, 대부분 유기 양이온과 무기 음이온으로 구성되어 있다. 상온에서 점도가 낮은 액체일 경우, 이온성 액체를 '상온 이온성 액체'(room temperature ionic liquids [RTILs])라 부르며, 최근 '상온 이온성 액체'는 유기 합성 반응, 촉매 반응, 전기화학 공정(electrochemical processes), 그리고 나노재료(nanomaterial) 합성에서 새로운 반응 용매로서 폭넓은 주목을 받고 있다(T. Welton, Chem. Rev., 1999, 99, 2071). 널리 사용되고 있는 전통적인 유기용매와 비교하여 '상온 이온성 액체'는 높은 온도에서의 안정하고, 무시할 정도의 증기압을 가지며, 재사용이 가능하고, 비가연성이라는 친환경적인 장점을 가지므로, 기존의 휘발성 유기 용매를 대체할 수 있는 친환경 용매(green solvent)로 여겨진다.Ionic liquids are defined as organic salts that melt below 100 ° C and are mostly composed of organic cations and inorganic anions. For liquids with low viscosity at room temperature, ionic liquids are called room temperature ionic liquids (RTILs). Recently, room temperature ionic liquids are used for organic synthesis, catalysis and electrochemical processes ( Wide attention has been given to new reaction solvents in electrochemical processes and nanomaterial synthesis (T. Welton, Chem. Rev., 1999, 99, 2071). Compared to conventional organic solvents, which are widely used, 'room temperature ionic liquids' are ecological advantages of stable, negligible vapor pressure at high temperature, reusable, and non-flammable, so that they are conventional volatile organic solvents. It is considered to be a green solvent that can replace.

에틸암모늄 니트레이트(Ethylammonium nitrate)가 1914년에 처음 발표된 이 래, 이미다졸륨(imidazolium), 피리디늄(pyridinium), 암모늄(ammonium), 포스포늄(phosphonium) 등을 포함한 수많은 상온 이온성 액체(RTILs)의 양이온이 개발되었다. 이들 중 1-부틸-3-메틸이미다졸륨(1-butyl-3-methylimidazolium ([bmim]))과 같은 1,3-디알킬이미다졸륨 양이온(1,3-dialkyl imidazolium cations)이 가장 일반적인 상온 이온성 액체(RTILs)로 사용되고 있다(그림 1).Since ethylammonium nitrate was first published in 1914, numerous room temperature ionic liquids, including imidazolium, pyridinium, ammonium, phosphonium, etc. Cations of RTILs) have been developed. Of these, 1,3-dialkyl imidazolium cations such as 1-butyl-3-methylimidazolium ([bmim]) are the most common. It is used as room temperature ionic liquids (RTILs) (Figure 1).

Figure 112009075196023-pat00002
Figure 112009075196023-pat00002

그림 1. 1-부틸-3-메틸이미다졸륨(1-Butyl-3-methylimidazolium ([bmim]))과 1-부틸-2,3-디메틸이미다졸륨(1-butyl-2,3-dimethylimidazolium ([bdmim])) 이온성액체.Figure 1. 1-Butyl-3-methylimidazolium (1-Butyl-3-methylimidazolium ([bmim])) and 1-butyl-2,3-dimethylimidazolium (1-butyl-2,3-dimethylimidazolium ([bdmim])) Ionic liquid.

이러한 1,3-디알킬이미다졸륨 양이온(1,3-dialkylimidazolium cation)의 C-2위치의 수소는 acidic하여 약염기 조건에서 쉽게 제거되어 카벤(carbene)을 형성하는데, 이렇게 형성된 카벤(carbene)은 금속 촉매에 리간드로 작용하여 Heck 반응과 Suzuki coupling에서 금속 촉매의 활성을 증가시키는 유리한 영향을 미친다. 그러나, Horner-Wadsworth-Emmons 반응, Knoevenagel condensation, ClaisenSchmidt condensation, 그리고 Baylis-Hillman 반응에서의 카벤(carbene)은 원하는 화학 변화를 상당 부분 방해한다(S. Chowdhury, R. S. Mohan and J. L. Scott, Tetrahedron, 2007, 63, 2363). 특히, Baylis-Hillman 반응의 경우, 하기 [반응식 1]과 같이 C-2 수소가 제거된 후, 형성된 이미다졸륨 카벤(imidazolium carbene)이 친핵체(nucleophile)로 작용하여, 직접 알데히드와 반응하게 되고 부산물 3을 생성한다(V. K. Aggarwal, I. Emme and A. Mereu, Chem . Commun ., 2002, 1612). Hydrogen at the C-2 position of the 1,3-dialkylimidazolium cation is acidic and easily removed under weak base conditions to form carbene. The carbene thus formed It acts as a ligand to the metal catalyst, which has the beneficial effect of increasing the activity of the metal catalyst in Heck reaction and Suzuki coupling. However, carbene in the Horner-Wadsworth-Emmons reaction, Knoevenagel condensation, Claisen Schmidt condensation, and Baylis-Hillman reaction significantly interfere with the desired chemical change (S. Chowdhury, RS Mohan and JL Scott, Tetrahedron , 2007 , 63 , 2363). In particular, in the Baylis-Hillman reaction, after the C-2 hydrogen is removed as shown in [Scheme 1], the imidazolium carbene formed as a nucleophile reacts directly with the aldehyde and is a byproduct. 3 is generated (VK Aggarwal, I. Emme and A. Mereu, Chem . Commun ., 2002 , 1612).

[반응식 1] 1-부틸-3-메틸이미다졸륨(1-butyl-3-methylimidazolium ([bmim])) 이온성 액체와 벤즈알데히드(benzaldehyde)의 부반응[Scheme 1] Side reaction of 1-butyl-3-methylimidazolium ([bmim]) ionic liquid with benzaldehyde

Figure 112009075196023-pat00003
Figure 112009075196023-pat00003

또한, [반응식 1]과 같은 부반응은 1-부틸-2,3-디메틸이미다졸륨(1-butyl-2,3-dimethyl imidazolium([bdmim]))의 C-2 위치에 메틸치환체를 도입하여 C-2 수소제거 반응을 억제할 수 있으나, C-2 메틸기 또한 트리에틸아민 염 기(triethylamine base)의 존재 하에서 천천히 proton exchange가 일어난다(S. T. Handy and M. Okello, J. Org . Chem., 2005, 70, 1915). 따라서, 공지된 이온성 액체는 염기성 조건 반응에 적합하지 않은 문제점이 있다. In addition, a side reaction as shown in [Scheme 1] introduces a methyl substituent at the C-2 position of 1-butyl-2,3-dimethyl imidazolium ([bdmim]). Although the C-2 hydrogen removal reaction can be suppressed, the C-2 methyl group also slowly undergoes proton exchange in the presence of triethylamine base (ST Handy and M. Okello, J. Org . Chem ., 2005 , 70 , 1915). Thus, known ionic liquids have a problem that they are not suitable for basic conditional reactions.

본 발명의 목적은 염기성 조건에서 화학적으로 안정한 반응용매로서 이온성 액체인 1,3-디알킬-1,2,3-트리아졸륨 염을 제공하기 위한 것이다. It is an object of the present invention to provide a 1,3-dialkyl-1,2,3-triazolium salt which is an ionic liquid as a chemically stable reaction solvent under basic conditions.

본 발명의 다른 목적은 1,3-디알킬-1,2,3-트리아졸륨 염의 1,3 위치에 서로 다른 알킬 치환체를 도입하여 물리 화학적 성질을 조절할 수 있도록 효율적인 합성방법을 제공하기 위한 것이다.Another object of the present invention is to provide an efficient method for synthesizing physicochemical properties by introducing different alkyl substituents at positions 1,3 of 1,3-dialkyl-1,2,3-triazolium salt.

본 발명은 반응용매로서의 하기 화학식 1의 이온성 액체를 제공한다:The present invention provides an ionic liquid of formula 1 as a reaction solvent:

[화학식 1][Formula 1]

Figure 112009075196023-pat00004
Figure 112009075196023-pat00004

상기 식에서, R1 및 R2는 각각 C1-C4의 알킬기 또는 벤질기이며, X는 I (iodide), NTf2(bis((trifluoromethyl)sulfonyl)amide), OTf (trifluoromethylsulfonate), PF6(hexafluorophosphate) 또는 BF4(tetrafluoroborate) 이다.Wherein R 1 and R 2 are each C 1 -C 4 alkyl or benzyl groups, X is I (iodide), NTf 2 (bis ((trifluoromethyl) sulfonyl) amide), OTf (trifluoromethylsulfonate), PF 6 ( hexafluorophosphate) or BF 4 (tetrafluoroborate).

본 발명의 [화학식 1] 화합물에서, R1 및 R2는 각각 벤질기, 메틸기 또는 n-부틸기인 것이 바람직하며, R1 및 R2는 모두 n-부틸기인 것이 보다 더 바람직하다. In the compound of formula 1, R 1 and R 2 are each preferably a benzyl group, a methyl group or an n-butyl group, and more preferably both R 1 and R 2 are n-butyl groups.

또한, 본 발명의 [화학식 1] 화합물에서, R1 및 R2는 각각 서로 상이한 것이 바람직하며, R1은 벤질기이고 R2는 메틸기이거나, R1은 n-부틸기이고 R2는 메틸기인 것이 보다 더 바람직하다. In addition, in the compound of Formula 1, R 1 and R 2 are preferably different from each other, R 1 is a benzyl group and R 2 is a methyl group, R 1 is an n-butyl group and R 2 is a methyl group. Even more preferred.

본 발명에서 "반응용매"는 일반적으로 유기 화학반응에 사용되는 용매를 의미하므로, 전류를 통과시키는 전해액과는 전혀 상이한 것을 의미한다. 특히 염기성 조건의 반응에 사용되는 "반응용매"가 바람직하다. 여기서, 염기성 조건의 반응은 반응 중에 약염기 또는 강염기가 사용되거나 반응 중에 이들이 생성되는 반응을 의미하며, 예를 들어, Horner-Wadsworth-Emmons 반응, Knoevenagel condensation 반응, Claisen-Schmidt condensation 반응, 및 Baylis-Hillman 반응 등이 있다. In the present invention, since "reaction solvent" generally means a solvent used for organic chemical reaction, it means a completely different from the electrolyte that passes the current. In particular, the "reaction solvent" used for reaction of basic conditions is preferable. Here, the reaction under basic conditions refers to a reaction in which weak or strong bases are used during the reaction or in which they are generated during the reaction, for example, Horner-Wadsworth-Emmons reaction, Knoevenagel condensation reaction, Claisen-Schmidt condensation reaction, and Baylis-Hillman Reaction and the like.

또한, 본 발명은 하기 단계를 포함하는 [화학식1] 화합물에서 X가 요오도인 [화학식 6] 화합물을 제조하는 방법을 제공한다:The present invention also provides a method for preparing a compound of Formula 6, wherein X is iodo in a compound of Formula 1, comprising the following steps:

a) 하기 [화학식 2] 화합물과 트리알킬실릴아세틸렌을 반응시켜 [화학식 3] 화합물을 제조하는 단계;a) preparing a compound of Chemical Formula 3 by reacting a compound of Chemical Formula 2 with trialkylsilylacetylene;

b) [화학식 3]화합물을 불화염, 산 또는 염기하에서 반응시켜 [화학식 4] 화합물을 제조하는 단계; 및b) preparing a compound of Chemical Formula 4 by reacting the compound of Chemical Formula 3 under fluoride, acid or base; And

c) [화학식 4] 화합물과 [화학식 5] 화합물과 반응시켜 [화학식 6] 화합물을 제조하는 단계를 포함하는 [화학식 6] 화합물의 제조방법.c) A method for preparing the compound of Formula 6, comprising the step of reacting the compound with the compound of Formula 4 to produce the compound of Formula 6.

[화학식 2][Formula 2]

Figure 112009075196023-pat00005
Figure 112009075196023-pat00005

[화학식 3] (3)

Figure 112009075196023-pat00006
Figure 112009075196023-pat00006

[화학식 4] [Formula 4]

Figure 112009075196023-pat00007
Figure 112009075196023-pat00007

[화학식 5][Chemical Formula 5]

Figure 112009075196023-pat00008
Figure 112009075196023-pat00008

[화학식 6] [Formula 6]

Figure 112009075196023-pat00009
Figure 112009075196023-pat00009

[화학식 1] [Formula 1]

Figure 112009075196023-pat00010
Figure 112009075196023-pat00010

상기 식에서, Where

R1은 C1-C4의 알킬기 또는 벤질기이며, R 1 is a C 1 -C 4 alkyl group or benzyl group,

R2는 C1-C4의 알킬기이고,R 2 is an alkyl group of C 1 -C 4 ,

X는 NTf2(bis((trifluoromethyl)sulfonyl)amide), OTf(trifluoromethylsulfonate), PF6(hexafluorophosphate) 또는 BF4(tetrafluoroborate) 이다.X is NTf 2 (bis ((trifluoromethyl) sulfonyl) amide), OTf (trifluoromethylsulfonate), PF 6 (hexafluorophosphate) or BF 4 (tetrafluoroborate).

본 발명에서 출발물질인 [화학식 2]화합물을 시중에서 용이하게 구입할 수 있는 물질이거나, 공지된 통상의 방법으로 제조할 수 있다. 예를 들어, [화학식2] 화합물이 n-부틸아자이드인 경우 n-부틸클로라이드와 소듐아자이드를 DMF(dimethylforamide) 용매 중에서 가열 교반시켜 제조할 수 있다.Compound [Formula 2] as a starting material in the present invention can be easily purchased on the market, or can be prepared by a known conventional method. For example, when the compound of Formula 2 is n-butyl azide, n-butyl chloride and sodium azide may be prepared by heating and stirring in a DMF (dimethylforamide) solvent.

또한, 본 발명의 반응 물질인 트리알킬실릴아세틸렌은 예를 들어, 트리메틸실릴아세틸렌, 트리에틸실릴아세틸렌, t-부틸디메틸실릴아세틸렌, 디메틸페닐실릴아세틸렌, 트리이소프로필실릴아세틸렌 등과 같이 다양한 실릴아세틸렌을 사용할 수 있으며, 이는 시중에서 구입하거나 트리알킬실릴할라이드와 아세틸렌을 반응시켜 제조할 수 있다. In addition, the trialkylsilylacetylene which is a reactant of the present invention may be used in various silylacetylenes such as, for example, trimethylsilylacetylene, triethylsilylacetylene, t-butyldimethylsilylacetylene, dimethylphenylsilylacetylene, triisopropylsilylacetylene, and the like. It can be purchased commercially or prepared by reacting trialkylsilyl halide with acetylene.

본 발명의 제조방법에서, a)단계 반응은 실온에서 촉매없이 반응이 진행되기도 하나, 반응시간이 10일 이상 길어질 수 있다. 따라서, 가열 또는 구리촉매하에서 수행되는 것이 바람직하다. 여기서 가열은 약 50 내지 120 ℃에서 반응시킬 수 있으며, 60 내지 100 ℃가 보다 더 바람직하다. In the production method of the present invention, step a) the reaction may proceed without the catalyst at room temperature, but the reaction time may be longer than 10 days. Therefore, it is preferably carried out under heating or copper catalyst. The heating can here be reacted at about 50 to 120 ° C., with 60 to 100 ° C. even more preferred.

또한, a)단계의 구리촉매는 구리1 및 2가 모두 사용가능하며, 그 예로, 황산구리(CuSO4), 구리(II) 아세테이트(Cu(OAc)2), 염화제2구리(CuCl2), 염화제1구리(CuCl), 브롬화제1구리(CuBr), 요오드화제1구리(CuI) 등을 사용할 수 있으며, 황산구리나 요오드화제1구리가 보다 바람직하다. 또한, 구리(II)가 촉매를 사용할 때는 소듐아스코르베이트 등과 같은 환원제와 함께 사용하는 것이 바람직하며, 구리(I)가 촉매를 사용할 때는 트리알킬아민, 탄산수소나트륨(NaHCO3)과 같은 염기를 함께 사용할 수도 있다. 여기서 구리촉매의 사용량은 출발물질인 [화학식2] 화합물의 몰대비 0.01 내지 0.5 몰 가량 사용하는 것이 바람직하며, 0.05 몰 사용하는 것이 보다 더 바람직하다. 그러나, 이의 사용량은 반응 온도, 반응 용매의 종류에 따라 달라질 수 있다. In addition, the copper catalyst of step a) may use both copper 1 and 2, for example, copper sulfate (CuSO 4 ), copper (II) acetate (Cu (OAc) 2 ), cupric chloride (CuCl 2 ), Cuprous chloride (CuCl), cuprous bromide (CuBr), cuprous iodide (CuI) and the like can be used, with cuprous sulfate and cuprous iodide being more preferred. In addition, when copper (II) uses a catalyst, it is preferable to use it with a reducing agent such as sodium ascorbate. When copper (I) uses a catalyst, bases such as trialkylamine and sodium hydrogencarbonate (NaHCO 3 ) are used. Can also be used together. The copper catalyst is preferably used in an amount of about 0.01 to 0.5 moles, more preferably 0.05 moles, relative to the mole of the starting compound [Formula 2]. However, its amount may vary depending on the reaction temperature and the type of reaction solvent.

본 발명의 제조방법에서, a) 단계의 반응용매는 극성 용매가 바람직하며, 예 를 들어, DMF, DMSO(dimethylsulfoxide), C1-C4 알코올과 물의 혼합 용매, THF, acetonitrile, toluene, benzene, methylenechloride, chloroform 등을 사용할 수 있다. 반응 온도는 상온(15 내지 30 ℃)이 바람직하며, 반응 시간은 1 내지 48시간이 바람직하나, 반응온도, 촉매의 사용량에 따라 달라질 수 있다. In the preparation method of the present invention, the reaction solvent of step a) is preferably a polar solvent, for example, DMF, DMSO (dimethylsulfoxide), a mixed solvent of C 1 -C 4 alcohol and water, THF, acetonitrile, toluene, benzene, methylenechloride, chloroform, etc. can be used. The reaction temperature is preferably room temperature (15 to 30 ℃), the reaction time is preferably 1 to 48 hours, it may vary depending on the reaction temperature, the amount of the catalyst used.

본 발명의 제조방법에서, b)단계의 불화염은 예를 들어, KF, Bu4NF과 같이 F- 이온이 들어간 시약의 염을 사용할 수 있고, 산 또는 염기는 예를, 들어 HF과 같이 F- 이온이 들어간 시약의 산, 또는 K2CO3, LiOH, NaOH 등과 같은 염기를 사용할 수 있으며, TBAF(Tetra-n-butylammonium fluoride)가 보다 더 바람직하다. 4차 알킬암모늄염의 사용량은 [화학식 3] 화합물의 몰대비 1 내지 2 몰이 바람직하며, 반응용매는 THF, diethylether, acetonitrile, toluene, benzene, methylenechloride, chloroform 등을 사용할 수 있으며, 반응 시간 및 반응 온도는 a)단계에서 언급한 바와 같다. In the production method of the present invention, the fluoride salt of step b) may be used, for example, salts of reagents containing F- ions such as KF, Bu 4 NF, and acids or bases, for example, F, such as HF. Acids of reagents containing ions, or bases such as K 2 CO 3 , LiOH, NaOH and the like can be used, with TBAF (Tetra-n-butylammonium fluoride) being more preferred. The amount of the quaternary alkylammonium salt is preferably 1 to 2 moles relative to the mole of the compound [3], and the reaction solvent may be THF, diethylether, acetonitrile, toluene, benzene, methylenechloride, chloroform, and the reaction time and reaction temperature. As mentioned in step a).

본 발명의 제조방법에서, c)단계의 반응 물질인 [화학식 5] 화합물인 C1-C4알킬 요오드 화합물은 구체적으로 요오드화메틸, 요오드화에틸, 요오드화프로필, 요오드화이소프로필, 요오드화n-부틸, 요오드화이소부틸 또는 요오드화t-부틸이며, 요오드화메틸 또는 요오드화n-부틸이 바람직하다. c) 단계의 반응 온도는 약 20 내지 약 100 ℃이 바람직하며, 70 내지 90 ℃가 보다 바람직하고, 반응시간은 12시 간 내지 30시간이 바람직하다. 반응용매는 별도로 사용하지 않아도 되며, 사용할 경우, THF, diethylether, acetonitrile, toluene, benzene, methylenechloride, chloroform, DMF, DMSO 등을 사용할 수 있다.In the preparation method of the present invention, the C 1 -C 4 alkyl iodide compound, which is the reactant of step c), is specifically methyl iodide, ethyl iodide, propyl iodide, isopropyl iodide, n-butyl iodide, and iodide. Isobutyl or t-butyl iodide, with methyl iodide or n-butyl iodide preferred. The reaction temperature of step c) is preferably about 20 to about 100 ° C, more preferably 70 to 90 ° C, and the reaction time is preferably 12 hours to 30 hours. The reaction solvent does not need to be used separately, and when used, THF, diethylether, acetonitrile, toluene, benzene, methylenechloride, chloroform, DMF, DMSO, and the like can be used.

본 발명은 또한, 상기 [화학식 6] 화합물의 제조방법에 추가하여 [화학식 6] 화합물과 LiNTf2, KOTf, LiPF6 또는 AgBF4과 반응시켜 하기 [화학식 1] 화합물을 제조하는 [화학식 1]화합물의 제조방법을 제공한다. The present invention is a compound of [Formula 1] to produce a compound of the formula [1] by reacting with the compound [Formula 6] and LiNTf 2 , KOTf, LiPF 6 or AgBF 4 in addition to the method for preparing the compound [Formula 6] It provides a method of manufacturing.

[화학식 1] [Formula 1]

Figure 112009075196023-pat00011
Figure 112009075196023-pat00011

상기 식에서, Where

R1은 C1-C4의 알킬기 또는 벤질기이며, R 1 is a C 1 -C 4 alkyl group or benzyl group,

R2는 C1-C4의 알킬기이고,R 2 is an alkyl group of C 1 -C 4 ,

X는 NTf2(bis((trifluoromethyl)sulfonyl)amide), OTf(trifluoromethylsulfonate), PF6(hexafluorophosphate) 또는 BF4(tetrafluoroborate) 이다.X is NTf 2 (bis ((trifluoromethyl) sulfonyl) amide), OTf (trifluoromethylsulfonate), PF 6 (hexafluorophosphate) or BF 4 (tetrafluoroborate).

본 발명의 [화학식 1] 화합물 제조방법에서, LiNTf2, KOTf, LiPF6 또는 AgBF4의 사용량은 [화학식 6] 화합물의 몰량 대비 약 0.9 내지 1.1 몰 사용하는 것이 바람직하며, 1 몰 사용하는 것이 보다 더 바람직하다. 이때 반응용매는 물을 사용할 수 있으며, 반응 온도는 약 20 내지 약 60 ℃이 바람직하며, 약 40 ℃가 보다 바람직하며, 반응시간은 12 시간 내지 약 36시간이 바람직하나, 반응온도에 따라 달라질 수 있다.In the method of preparing the compound of Formula 1, the amount of LiNTf 2 , KOTf, LiPF 6 or AgBF 4 is preferably used in an amount of about 0.9 to 1.1 moles, more preferably 1 mole, relative to the molar amount of the compound of Formula 6; More preferred. In this case, the reaction solvent may be water, the reaction temperature is preferably about 20 to about 60 ℃, more preferably about 40 ℃, the reaction time is preferably 12 hours to about 36 hours, it may vary depending on the reaction temperature have.

본 발명의 화합물인 1-벤질-3-메틸-1,2,3-트리아졸륨 이온성 액체를 합성하는 방법을 예를 들어보면 다음의 [반응식 2]와 같다: For example, a method of synthesizing the compound of the present invention 1-benzyl-3-methyl-1,2,3-triazolium ionic liquid is shown in Scheme 2 below:

[반응식 2] 1-벤질-3-Scheme 2 1-benzyl-3- 메틸methyl -1,2,3-트리아졸륨([-1,2,3-triazolium ([ BnmTrBnmTr ][X]) 이온성 액체 합성] [X]) Ionic Liquid Synthesis

Figure 112009075196023-pat00012
Figure 112009075196023-pat00012

(a) CuSO4, Sodium ascorbate, t-BuOH/H2O (1/1), rt, 1 d; (a) CuSO 4 , Sodium ascorbate, t- BuOH / H 2 O (1/1), rt, 1 d;

(b) TBAF, THF, rt, 6 h; (b) TBAF, THF, rt, 6 h;

(c) CH3I, 80 ℃, 17 h; (c) CH 3 I, 80 ° C, 17 h;

(d) (9a): LiNTf2, H2O, 40 ℃, 1 d; (9b): KOTf, H2O, 40 ℃, 1 d; (9c): LiPF6, H2O, 40 ℃, 1 d; (9d): AgBF4, H2O, 40 ℃, 1 d. (d) ( 9a ): LiNTf 2 , H 2 O, 40 ° C., 1 d; ( 9b ): KOTf, H 2 O, 40 ° C., 1 d; ( 9c ): LiPF 6 , H 2 O, 40 ° C., 1 d; ( 9d ): AgBF 4 , H 2 O, 40 ° C., 1 d.

벤질아자이드(benzyl azide, 4)와 1-트리메틸실릴아세틸렌(1-trimethylsilylacetylene, 5)을 반응 물질로 하여 구리를 촉매로 한, Huisgen 1,3-dipolar cycloaddition으로 손쉽게 합성할 수 있다(반응식 2). 위 반응은 "click" 반응이라 하며 1, 4 위치에 치환체가 있는 1,2,3-트리아졸의 합성에 유용하다. 본 발명에서는 1-트리메틸실릴아세틸렌을 이용하여 "click" 반응을 한 후, 1,2,3-트리아졸의 4번 위치에 도입된 트리메틸실릴기를 TBAF을 이용하여 제거하는 방법으로 4번 위치의 치환체가 없고, 1 위치에만 치환체를 도입하는 방법을 고안하여 사용하였다. 그 후 1번 치환체와 다른 다양한 알킬할로겐을 사용한 알킬화반응은 1,3위치에 서로 다른 치환체를 손쉽게 도입할 수 있다. Benzyl azide ( 4 ) and 1-trimethylsilylacetylene ( 5 ) can be easily synthesized using copper-catalyzed Huisgen 1,3-dipolar cycloaddition as a reaction material (Scheme 2) . This reaction is called a "click" reaction and is useful for the synthesis of 1,2,3-triazoles having substituents at positions 1 and 4. In the present invention, after the "click" reaction using 1-trimethylsilylacetylene, the substituent at position 4 by removing the trimethylsilyl group introduced at position 4 of 1,2,3-triazole using TBAF And devised a method of introducing a substituent in only one position. Subsequently, the alkylation reaction using Substituent No. 1 and various other alkylhalogens can easily introduce different substituents at positions 1 and 3.

1-벤질-1,2,3-트리아졸(1-Benzyl-1,2,3-triazole, 7)을 1당량의 요오드화 메틸 (methyl iodide)과 80 ℃에서 반응하여 고순도의 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염(1-benzyl-3-methyl-1,2,3-triazolium iodide salt, 8)을 정량적으로 얻을 수 있었다. 8과 LiNTf2, KOTf, LiPF6, 또는 AgBF4과 음이온 치환반응을 하여 다양한 음이온의 1-벤질-3-메틸-1,2,3-트리아졸륨염 9a-9d를 얻을 수 있었다. 9a와 9b는 상온에서 액체 상태이고 9c와 9d는 100 ℃ 이하의 녹는점를 가지는 고체이므로 9a-9d는 이온성 액체라 규정할 수 있다. 1-benzyl-1,2,3-triazole (1-Benzyl-1,2,3-triazole, 7 ) was reacted with 1 equivalent of methyl iodide at 80 ° C. to obtain high-purity 1-benzyl-3 -Methyl-1,2,3-triazolium iodine salt (1-benzyl-3-methyl-1,2,3-triazolium iodide salt, 8 ) was obtained quantitatively. 8 and LiNTf 2 , KOTf, LiPF 6 , or AgBF 4 were subjected to an anion substitution reaction to obtain 1-benzyl-3-methyl-1,2,3-triazolium salt 9a-9d of various anions. Since 9a and 9b are liquid at room temperature and 9c and 9d are solids having a melting point of 100 ° C. or lower, 9a-9d can be defined as an ionic liquid.

본 발명의 화합물인 1-부틸-3-메틸-1,2,3-트리아졸륨 이온성 액체를 합성하는 방법을 예를 들어보면 다음의 [반응식 3]와 같다: For example, a method of synthesizing the compound of the present invention 1-butyl-3-methyl-1,2,3-triazolium ionic liquid is shown in Scheme 3 below:

[반응식 3]1-부틸-3-1-Butyl-3- 메틸methyl -1,2,3-트리아졸륨([-1,2,3-triazolium ([ bmTrbmTr ][X]) 이온성 액체의 합성 ] [X]) Synthesis of Ionic Liquids

Figure 112009075196023-pat00013
Figure 112009075196023-pat00013

(a) NaN3, DMF, 80 ℃, 20 h. (b) 5, CuI, DMF, 80 ℃, 40 h.; (c) TBAF, THF, rt, 6 h.; (d) CH3I, 80 ℃, 1 d.; (e) (14a): LiNTf2, H2O, 40 ℃, 1 d.; (14b): KOTf, H2O, 40 ℃, 1 d.; (14c): LiPF6, H2O, 40 ℃, 1 d.; (14d): AgBF4, H2O, 40 ℃, 1 d.(a) NaN 3 , DMF, 80 ° C., 20 h. (b) 5 , CuI, DMF, 80 ° C., 40 h .; (c) TBAF, THF, rt, 6 h .; (d) CH 3 I, 80 ° C, 1 d .; (e) ( 14a ): LiNTf 2 , H 2 O, 40 ° C., 1 d .; ( 14b ): KOTf, H 2 O, 40 ° C., 1 d .; ( 14c ): LiPF 6 , H 2 O, 40 ° C., 1 d .; ( 14d ): AgBF 4 , H 2 O, 40 ° C., 1 d.

1-부틸-3-메틸-1,2,3-트리아졸륨염([bmTr][X])은 가장 널리 사용되는 1-부틸-3-메틸 이미다졸륨([bmim][X]) 이온성 액체와 구조적으로 유사하다. 1-부틸-3-메틸-1,2,3-트리아졸륨염([bmTr][X])(14a-14d)은 세 단계로 합성하였다(반응식 4). 부틸클로라이드(n-Butyl chloride, 10)와 소듐 아자이드(NaN3)를 출발 물질로 하여 부틸 아자이드(n-butyl azide)를 생성하고, 반응을 종료하지 않고 직접 1-트리메틸실릴아세틸렌을 가하여 Cu를 촉매로 한 "click" 반응을 시행한다. 이는 벤질아자이드(benzyl azide, 4)의 click 반응과 다르게 1-부틸-4-트리메틸실릴-1,2,3-트리아졸(4-TMS-substituted 1,2,3-triazole, 11)과 TMS가 제거된 1-부틸-1,2,3-트리아졸 (1-butyl-1,2,3-triazole, 12)를 생성하였다. TBAF을 사용하여 TMS를 제거하여 11에서 12를 합성하고, 80 ℃에서 요오드화 메틸(CH3I)과 반응하여 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드염(13)을 97%의 수율로 얻을 수 있었다. 요오드염 13과 LiNTf2, KOTf, LiPF6, 또는 AgBF4의 음이온 치환반응으로 원하는 1-부틸-3-메틸-1,2,3-트리아졸륨염(14a-14d)를 얻을 수 있었다. 합성한 1-부틸-3-메틸-1,2,3-트리아졸륨염, 13과 14a-14d, 모두 상온에서 액체 상태로 존재하였다.1-butyl-3-methyl-1,2,3-triazolium salt ([bmTr] [X]) is the most widely used 1-butyl-3-methyl imidazolium ([bmim] [X]) ionic Structurally similar to liquid. 1-Butyl-3-methyl-1,2,3-triazolium salt ([bmTr] [X]) ( 14a-14d ) was synthesized in three steps (Scheme 4). Butyl chloride (n-Butyl chloride, 10 ) and sodium azide (NaN 3 ) were used as starting materials to form butyl azide (n-butyl azide), and 1-trimethylsilylacetylene was added directly without terminating the reaction. A "click" reaction is carried out with the catalyst. Unlike the click reaction of benzyl azide ( 4 ), it is 1-butyl-4-trimethylsilyl-1,2,3-triazole (4-TMS-substituted 1,2,3-triazole, 11 ) and TMS. To give 1-butyl-1,2,3-triazole (1-butyl-1,2,3-triazole, 12 ). TMS was removed using TBAF to synthesize 11 to 12 , and reacted with methyl iodide (CH 3 I) at 80 ° C. to prepare 1-butyl-3-methyl-1,2,3-triazolium iodide salt ( 13 ). Yield was 97%. The desired 1-butyl-3-methyl-1,2,3-triazolium salt ( 14a-14d ) was obtained by anion substitution reaction between iodine salt 13 and LiNTf 2 , KOTf, LiPF 6 , or AgBF 4 . Synthesized 1-butyl-3-methyl-1,2,3-triazolium salt, 13 and 14a-14d , were all in liquid state at room temperature.

한편, 1H-1,2,3-트리아졸을 알킬화하는 방법 중, 로 1H-1,2,3-트리아졸(1H- 1,2,3-triazole)에 직접 알킬화(alkylation)를 하는 경우, 위치이성체(regioisomers)의 혼합물이 생성되거나, 디알킬화가 일어난 (symmetrically dialkylated) 화합물이 생성되기 때문에, 1-벤질-3-메틸과 같이 1,3 위치에 서로 다른 치환체가 도입된 (unsymmetrically substituted) 1,3-디알킬-1,2,3-트리아졸륨 염의 합성에는 문제가 있다(반응식 4). 본 발명에서 사용한 1-트리메틸실릴아세틸렌을 이용한 "click" 반응은 이런 문제점을 해결하였다. 특히 이온성 액체는 결정화를 막기 위해 구조적 비대칭성이 중요하며, 그 물리 화학적 성질을 조절하기 위해 다양한 구조의 치환체 도입이 용이해야 하므로, 1,3 위치에 서로 다른 치환체를 용이하게 도입하는 것은 이온성 액체 개발에 매우 중요한 요소이다. On the other hand,, 1 H -1,2,3- triazole (1 H - 1,2,3-triazole) of a method for alkylating a 1 H -1,2,3- triazol-alkylation (alkylation) directly to the In this case, since a mixture of regioisomers is produced or a symmetrically dialkylated compound is produced, different substituents are introduced at positions 1 and 3 such as 1-benzyl-3-methyl (unsymmetrically). substituted) There is a problem in the synthesis of 1,3-dialkyl-1,2,3-triazolium salts (Scheme 4). The "click" reaction using 1-trimethylsilylacetylene used in the present invention solved this problem. In particular, ionic liquids are structurally asymmetric in order to prevent crystallization, and in order to control their physicochemical properties, it is necessary to easily introduce substituents of various structures, so it is easy to introduce different substituents at positions 1 and 3 It is a very important factor in the development of liquids.

[반응식 4] 1H-1,2,3-트리아졸에 직접 알킬화의 문제점 Scheme 4 Problems of alkylation directly to 1H-1,2,3-triazole

Figure 112009075196023-pat00014
Figure 112009075196023-pat00014

본 발명의 화합물인 1,3-디부틸-1,2,3-트리아졸륨 이온성 액체를 합성하는 방법을 예를 들어보면 다음의 [반응식 5]와 같다: For example, a method for synthesizing the 1,3-dibutyl-1,2,3-triazolium ionic liquid of the present invention is shown in Scheme 5 below:

[반응식 5] 1,3-Scheme 5 1,3- 디부틸Dibutyl -1,2,3-트리아졸륨([-1,2,3-triazolium ([ dbTrdbTr ][X]) 이온성 액체의 합성] [X]) Synthesis of Ionic Liquids

Figure 112009075196023-pat00015
Figure 112009075196023-pat00015

(a) NaH, n-butyliodide (5 equiv.), CH3CN, 80 ℃, 19 h.; (b) n-Butyliodide (1equiv.), Neat, 80 ℃, 15 h.; (c) (17a) LiNTf2, H2O, 40 ℃, 15 h.; (17b) KOTf, H2O, 40 ℃, 11 h.; (17c) LiPF6, H2O, 40 ℃, 22 h.; (17d) AgBF4, H2O, 40 ℃, 20 h.(a) NaH, n- butyliodide (5 equiv.), CH 3 CN, 80 ° C., 19 h .; (b) n- Butyliodide (1equiv.), Neat, 80 ° C., 15 h .; (c) ( 17a ) LiNTf 2 , H 2 O, 40 ° C., 15 h .; ( 17b ) KOTf, H 2 O, 40 ° C., 11 h .; ( 17c ) LiPF 6 , H 2 O, 40 ° C., 22 h .; ( 17d ) AgBF 4 , H 2 O, 40 ° C., 20 h.

1,3-디부틸-1,2,3-트리아졸륨염([dbTr][X])(17a-17d)는 할로겐화 알킬 (alkyl halide)를 사용하여 직접적인 알킬화 반응(alkylation)을 통하여 합성하였 다. 아세토니트릴(CH3CN)에서 1H-1,2,3-트리아졸(15)과 1당량의 수소화 나트륨(NaH)을 먼저 혼합하고, 여기에 과량의 부틸아이오다이드(n-butyl iodide)를 더하여 원하는 화합물 1,3-디부틸-1,2,3-트리아졸륨 요오드염 16을 75%의 수율로 얻었다(반응식 5). 다른 방법으로, 1-부틸-1,2,3-트리아졸(12)과 1당량의 부틸아이오다이드를 80 ℃에서 반응하여 95%의 수율로 동일한 화합물 16을 얻을 수 있었다. 1,3-디부틸-1,2,3-트리아졸륨 요오드염 16과 LiNTf2, KOTf, LiPF6, 또는 AgBF4의 치환반응으로 원하는 1,3-디부틸-1,2,3-트리아졸륨염 ([dbTr][X])(17a-17d)를 상온 이온성 액체로서 얻을 수 있었다. 1,3-dibutyl-1,2,3-triazolium salt ([dbTr] [X]) ( 17a-17d ) was synthesized by direct alkylation using alkyl halides. . 1 H -1,2,3-triazole ( 15 ) and 1 equivalent of sodium hydride (NaH) are first mixed in acetonitrile (CH 3 CN), followed by excess butyl iodide (n-butyl iodide). In addition, the desired compound 1,3-dibutyl-1,2,3-triazolium iodine salt 16 was obtained in a yield of 75% (Scheme 5). Alternatively, 1-butyl-1,2,3-triazole ( 12 ) and 1 equivalent of butyl iodide were reacted at 80 ° C. to obtain the same compound 16 in 95% yield. Substitution of 1,3-dibutyl-1,2,3-triazolium iodine salt 16 with LiNTf 2 , KOTf, LiPF 6 , or AgBF 4 1,3-dibutyl-1,2,3-triazole Cerium salt ([dbTr] [X]) ( 17a-17d ) could be obtained as a room temperature ionic liquid.

본 발명에서 합성한 [BnmTr], [bmTr], 그리고 [dbTr]인 세 가지 형태의 새로운 1,2,3-트리아졸륨 염인 9a, 9b, 13, 14a-14d, 16, 그리고 17a-17d는 상온에서 액체 상태이며 9c와 9d는 100 ℃ 이하에서 녹는 염 상태이다.The three new 1,2,3-triazolium salts, 9a , 9b , 13 , 14a - 14d , 16 , and 17a-17d , synthesized in the present invention, [BnmTr], [bmTr], and [dbTr], are at room temperature. Is in the liquid state and 9c and 9d are salts that melt at below 100 ° C.

본 발명의 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체는 음이온을 변화시켜 물 및 다양한 유기용매에 대한 섞임성을 변화시킬 수 있으므로 회수-재사용이 가능한 효과가 있으며, 기존의 1,3-디알킬-이미다졸륨 이온성 액체에 비해 염기성 조건에서 화학적으로 더욱 안정하여 염기성조건에서 진행하는 반응용매로 보다 적합하며, 특히 Baylis-Hillman 반응을 기존의 1,3-디알킬-이미다졸륨 이온성 액체보다 향상된 수득율을 제공하는 효과가 있다. Since the 1,3-dialkyl-1,2,3-triazolium ionic liquid of the present invention can change the mixing properties of water and various organic solvents by changing anions, there is an effect that can be recovered and reused. Compared to 1,3-dialkyl-imidazolium ionic liquid, the chemical is more stable under basic conditions and more suitable as a reaction solvent. It has the effect of providing improved yields over imidazolium ionic liquids.

또한, 본 발명의 제조방법은 1-트리메틸실릴아세틸렌을 이용하는 Huisgen 1,3-dipolar cycloaddition 반응을 사용하여 1,3 위치에 서로 다른 길이의 알킬기를 갖는 1,2,3-트리아졸륨 이온성 액체를 합성할 수 있었으며, 알킬기를 변화시켜 다양한 물리 화학적 성질을 갖는 이온성 액체를 합성할 수 있는 효과가 있다. In addition, the preparation method of the present invention uses a Huisgen 1,3-dipolar cycloaddition reaction using 1-trimethylsilylacetylene to prepare a 1,2,3-triazolium ionic liquid having alkyl groups having different lengths at 1,3 positions. It was able to synthesize, and by changing the alkyl group has the effect of synthesizing the ionic liquid having a variety of physical and chemical properties.

이하, 본 발명의 이해를 돕기 위하여 바람직한 제조예 및 실시예를 제시한다. 그러나 하기의 제조예 및 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 제조예 및 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred preparation examples and examples are provided to aid in understanding the present invention. However, the following Preparation Examples and Examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the Preparation Examples and Examples.

또한, 이하에서 언급된 시약 및 용매는 특별한 언급이 없는 한 Aldrich사, Alfa Aesar사, Acros사 또는 Cambridge Isotope Labortories사로부터 구입한 것이며, 1H-NMR 데이터는 Unity 400(Varian 사) 기계로 측정한 값이며, Mass 데이터는 JMS-AX 505wA와 JMS-HX/HX 110A(JEOL 사) 기계로 측정한 값이다.In addition, the reagents and solvents mentioned below were purchased from Aldrich, Alfa Aesar, Acros or Cambridge Isotope Labortories, unless otherwise specified, and 1 H-NMR data measured on a Unity 400 (Varian) machine. Mass data is measured by JMS-AX 505wA and JMS-HX / HX 110A (JEOL) machines.

<< 실시예Example A> 1-벤질-3- A> 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체의 합성  Synthesis of Ionic Liquids

<< 실시예Example A-1> 1-벤질-3- A-1> 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스( Vis ( 트리플루오로메틸술포Trifluoromethylsulfo 닐)아미드 염(9a)의 합성[Synthesis of nil) amide salt (9a) [ BnmTrBnmTr ][] [ NTfNTf 22 ]]

A-1-1 : 1-벤질-4-A-1-1: 1-benzyl-4- 트리메틸실릴Trimethylsilyl -1,2,3--1,2,3- 트리아졸(6)의Of triazole (6) 합성 synthesis

둥근 바닥 플라스크에 벤질아자이드 (0.266 g, 2.00 mmol), 트리메틸실릴아 세틸렌 (0.196 g, 2.00 mmol), 황산구리 (0.016g, 0.100mmol) 및 아스코르브산 나트륨(sodium ascorbate)(0.040 g, 0.200 mmol)를 t-부탄올과 물[1/1(v/v), 4 mL])에 녹여 상온에서 24시간 동안 교반하였다. 반응을 멈춘 뒤, 용매를 감압 농축하여 생성된 고체를 거르고, CH2Cl2로 씻었다. 여과액을 감압 농축하여 1-벤질-4-트리메틸실릴-1,2,3-트리아졸(6)(0.46 g, 100%)를 갈색 고체 상태로 얻었다. Benzyl azide (0.266 g, 2.00 mmol), trimethylsilylacetylene (0.196 g, 2.00 mmol), copper sulfate (0.016 g, 0.100 mmol) and sodium ascorbate (0.040 g, 0.200 mmol) in a round bottom flask ) Was dissolved in t -butanol and water [1/1 (v / v), 4 mL]) and stirred at room temperature for 24 hours. After the reaction was stopped, the solvent was concentrated under reduced pressure, and the resulting solid was filtered off and washed with CH 2 Cl 2 . The filtrate was concentrated under reduced pressure to give 1-benzyl-4-trimethylsilyl-1,2,3-triazole ( 6 ) (0.46 g, 100%) as a brown solid.

TLC: R f 0.14 (3:1(v/v)=hexane/EtOAc). mp: 54-56℃. 1H-NMR (400 MHz, CDCl3): δ 7.42 (s,1H), 7.38-7.36 (m,3H), 7.28 (d, 2H, J = 2.0Hz), 5.56 (s, 2H), 0.30 (s, 9H). 13C-NMR (100 MHz, CDCl3): δ 147.4, 135.2, 129.3, 128.9, 128.8, 128.3, 53.7, -0.9.LRMS (FAB) m/z (rel int): 91 ([C7H7]+, 63), 232 ([M+H]+, 100). HRMS m/z calcd for C12H18N3Si 232.1270; found 232.1270.TLC: R f 0.14 (3: 1 (v / v) = hexane / EtOAc). mp: 54-56 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 7.42 (s, 1H), 7.38-7.36 (m, 3H), 7.28 (d, 2H, J = 2.0 Hz), 5.56 (s, 2H), 0.30 ( s, 9H). 13 C-NMR (100 MHz, CDCl 3 ): δ 147.4, 135.2, 129.3, 128.9, 128.8, 128.3, 53.7, -0.9.LRMS (FAB) m / z (rel int): 91 ([C 7 H 7 ] + , 63), 232 ([M + H] + , 100). HRMS m / z calcd for C 12 H 18 N 3 Si 232.1270; found 232.1270.

A-1-2: 1-벤질-1,2,3-A-1-2: 1-benzyl-1,2,3- 트리아졸(7)의Triazole (7) 합성 synthesis

둥근 바닥 플라스크에 <실시예 A-1-1>에서 제조한 1-벤질-4-트리메틸실릴-1,2,3-트리아졸(6)(2.26 g, 9.78 mmol)를 THF 9.8 mL에 녹여 교반하였다. 여기에 테트라부틸암모늄 플로라이드(TBAF)(1M THF 용액, 11.7 mL, 11.7 mmol)를 천천히 가하였다. 이를 상온에서 6시간 동안 교반하고 반응을 멈춘 뒤 용매를 감압 농축한 후 컬럼 크로마토그래피(Hexane/EtOAc = 1/3(v/v))로 정제하여 1-벤질-1,2,3-트리 아졸 (7) (1.49 g, 96%)을 흰색의 고체 상태로 얻었다.1-benzyl-4-trimethylsilyl-1,2,3-triazole ( 6 ) (2.26 g, 9.78 mmol) prepared in <Example A-1-1> was dissolved in THF 9.8 mL in a round bottom flask. It was. Tetrabutylammonium fluoride (TBAF) (1M THF solution, 11.7 mL, 11.7 mmol) was slowly added thereto. After stirring for 6 hours at room temperature and stopping the reaction, the solvent was concentrated under reduced pressure and purified by column chromatography (Hexane / EtOAc = 1/3 (v / v)) to 1-benzyl-1,2,3-triazole ( 7 ) (1.49 g, 96%) was obtained in a white solid state.

TLC: R f 0.12 (3:1(v/v)= hexane/EtOAc). mp: 61-63 ℃. 1H-NMR (400 MHz, CDCl3): δ7.71 (s,1H), 7.47 (s,1H), 7.40-7.35 (m,3H), 7.28-7.25 (m,2H), 5.56 (s,2H). 13C-NMR (100 MHz, CDCl3): δ134.9, 134.5, 129.3, 129.0, 128.2, 123.5, 54.2. LRMS (FAB) m/z (rel int): 91 ([C7H7]+, 63), 160 ([M+H]+, 80). HRMS m/z calcd for C9H10N3 160.0875; found 160.0872.TLC: R f 0.12 (3: 1 (v / v) = hexane / EtOAc). mp: 61-63 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ7.71 (s, 1H), 7.47 (s, 1H), 7.40-7.35 (m, 3H), 7.28-7.25 (m, 2H), 5.56 (s, 2H). 13 C-NMR (100 MHz, CDCl 3 ): δ 134.9, 134.5, 129.3, 129.0, 128.2, 123.5, 54.2. LRMS (FAB) m / z (rel int): 91 ([C 7 H 7 ] + , 63), 160 ([M + H] + , 80). HRMS m / z calcd for C 9 H 10 N 3 160.0875; found 160.0872.

A-1-3 : 1-벤질-3-A-1-3: 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 요오드 염(8)의 합성 Synthesis of Iodine Salt (8) [ [ BnmTrBnmTr ][I]] [I]

5 mL 용량의 바이알에 <실시예 A-1-2>에서 제조한 1-벤질-1,2,3-트리아졸 (7)(1.97 g, 12.4 mmol)과 요오드화메틸 (1.76 g, 12.4 mmol)을 넣고 80 ℃에서 17 시간 동안 교반하였다. 17시간 뒤, 상온으로 식히고 감압 농축하여 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염(8)(3.62 g, 97%)을 연한 노란색의 고체 상태로 얻었다. In a 5-mL vial, 1-benzyl-1,2,3-triazole ( 7 ) (1.97 g, 12.4 mmol) and methyl iodide (1.76 g, 12.4 mmol) prepared in <Example A-1-2> And stirred at 80 ℃ for 17 hours. After 17 hours, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain 1-benzyl-3-methyl-1,2,3-triazolium iodine salt ( 8 ) (3.62 g, 97%) as a pale yellow solid.

mp: 127.5-129.5 ℃. 1H-NMR (400 MHz, CDCl3): δ 9.34 (brs, 1H), 9.19 (brs, 1H), 7.58-7.56 (m, 2H), 7.46-7.44 (m, 3H), 5.93 (s, 2H), 4.51 (s, 3H). 1H-NMR (400 MHz, DMSO-d 6): δ8.98 (d, 1H, J = 1.2Hz), 8.86 (d, 1H, J = 1.2Hz), 7.49-7.42 (m,5H), 5.89 (s, 2H), 4.30 (s, 3H). 13C-NMR (100 MHz, DMSO-d 6): δ 133.0, 132.1, 130.8, 129.2, 129.0, 128.8, 56.0, 40.0. LRMS (FAB) m/z (rel int): 91 ([C7H7]+, 24), 174 ([C10H12N3]+, 100). HRMS m/z calcd for C10H12N3 174.1031; found 174.1027.mp: 127.5-129.5 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 9.34 (brs, 1H), 9.19 (brs, 1H), 7.58-7.56 (m, 2H), 7.46-7.44 (m, 3H), 5.93 (s, 2H ), 4.51 (s, 3 H). 1 H-NMR (400 MHz, DMSO- d 6 ): δ 8.98 (d, 1H, J = 1.2 Hz), 8.86 (d, 1H, J = 1.2 Hz), 7.49-7.42 (m, 5H), 5.89 (s, 2 H), 4.30 (s, 3 H). 13 C-NMR (100 MHz, DMSO- d 6 ): δ 133.0, 132.1, 130.8, 129.2, 129.0, 128.8, 56.0, 40.0. LRMS (FAB) m / z (rel int): 91 ([C 7 H 7 ] + , 24), 174 ([C 10 H 12 N 3 ] + , 100). HRMS m / z calcd for C 10 H 12 N 3 174.1031; found 174.1027.

A-1-4 :1-벤질-3-A-1-4: 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스(트리플루오로메틸술포닐)아미Bis (trifluoromethylsulfonyl) ami 드 염(9a)의 합성Synthesis of De Salt (9a)

5 mL 용량의 바이알에 <실시예 A-1-3>에서 제조한 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염(8)(0.330 g, 1.10 mmol)과 LiNTf2 (Lithium bis((trifluoromethylsulfonyl))amide, 0.315 g, 1.10 mmol), 증류수 1.6 mL를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물 층을 CH2Cl2으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 목적하는 1-벤질-3-메틸-1,2,3-트리아졸륨 비스(트리플루오로메틸술포닐)아미드 염 (9a)(0.496 g, 100%)을 갈색의 액체 상태로 얻었다. In a 5 mL vial, 1-benzyl-3-methyl-1,2,3-triazolium iodine salt ( 8 ) (0.330 g, 1.10 mmol) and LiNTf 2 prepared in <Example A-1-3> (Lithium bis ((trifluoromethylsulfonyl)) amide, 0.315 g, 1.10 mmol) and 1.6 mL of distilled water were added thereto and stirred at 40 ° C. for 24 hours. After cooling to room temperature, the water layer was extracted with CH 2 Cl 2 . The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to obtain the desired 1-benzyl-3-methyl-1,2,3-triazolium bis (trifluoromethylsulfonyl) amide salt ( 9a ) ( 0.496 g, 100%) was obtained as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 8.48 (s,1H), 8.38 (s,1H), 7.45 (brs, 5H), 5.72 (s, 2H), 4.36 (s, 3H). 13C-NMR (100 MHz, CDCl3): δ 132.1, 130.7, 130.6, 130.6, 130.0, 129.6, 119.9 (q, J CF = 319.1 Hz), 57.8, 40.5. LRMS (FAB) m/z (rel int): (pos) 91 ([C7H7]+, 24), 174 ([C10H12N3]+, 100). HRMS m/z calcd for C10H12N3 174.1031; found 174.1027. Anal. Calcd for C12H12F6N4O4S2: C, 31.72; H, 2.66; N, 12.33; S, 14.11. Found: C, 31.76; H, 2.70; N, 12.34; S, 14.37. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.48 (s, 1H), 8.38 (s, 1H), 7.45 (brs, 5H), 5.72 (s, 2H), 4.36 (s, 3H). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.1, 130.7, 130.6, 130.6, 130.0, 129.6, 119.9 (q, J CF = 319.1 Hz), 57.8, 40.5. LRMS (FAB) m / z (rel int): (pos) 91 ([C 7 H 7 ] + , 24), 174 ([C 10 H 12 N 3 ] + , 100). HRMS m / z calcd for C 10 H 12 N 3 174.1031; found 174.1027. Anal. Calcd for C 12 H 12 F 6 N 4 O 4 S 2 : C, 31.72; H, 2. 66; N, 12.33; S, 14.11. Found: C, 31.76; H, 2. 70; N, 12.34; S, 14.37.

<< 실시예Example A-2> 1-벤질-3- A-2> 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 트리플루오로메탄설포네이트Trifluoromethanesulfonate 염(9b)의 합성 [ Synthesis of Salt (9b) [ BnmTrBnmTr ][] [ OTfOTf ]]

5 mL 용량의 바이알에 <실시예 A-1-3>에서 제조한 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염 (8) (1.00 g, 3.33 mmol)과 KOTf (Potassium trifluoromethylsulfonate, 0.670 g, 3.33 mmol), 증류수 4.8 mL를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 CH2Cl2으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 목적하는 1-벤질-3-메틸-1,2,3-트리아졸륨 트리플루오로메탄설포늄 염(9b)(0.619 g, 57%)을 갈색 액체 상태로 얻었다.In a 5 mL vial, 1-benzyl-3-methyl-1,2,3-triazolium iodide ( 8 ) (1.00 g, 3.33 mmol) and KOTf (Potassium) prepared in <Example A-1-3> trifluoromethylsulfonate, 0.670 g, 3.33 mmol) and 4.8 mL of distilled water were added and stirred at 40 ° C. for 24 hours. After cooling to room temperature, the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was washed with distilled water, dried over anhydrous MgSO 4, and then concentrated under reduced pressure to obtain the desired 1-benzyl-3-methyl-1,2,3-triazolium trifluoromethanesulfonium salt ( 9b ) (0.619 g, 57 %) Was obtained as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 8.90 (s, 1H), 8.78 (s, 1H), 7.51-7.49 (m, 2H), 7.46-7.44 (m, 3H), 5.81 (s, 2H), 4.42 (s, 3H). 13C-NMR (100 MHz, CDCl3): δ 132.4, 131.4, 131.0, 130.2, 129.7, 129.6, 120.7 (q, J CF = 318.3Hz), 57.7, 40.8. LRMS (FAB) m/z (rel int): (pos) 91 ([C7H7]+, 30), 174 ([C10H12N3]+, 100). HRMS m/z calcd for C10H12N3 174.1031; found 174.1035. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.90 (s, 1H), 8.78 (s, 1H), 7.51-7.49 (m, 2H), 7.46-7.44 (m, 3H), 5.81 (s, 2H ), 4.42 (s, 3 H). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.4, 131.4, 131.0, 130.2, 129.7, 129.6, 120.7 (q, J CF = 318.3 Hz), 57.7, 40.8. LRMS (FAB) m / z (rel int): (pos) 91 ([C 7 H 7 ] + , 30), 174 ([C 10 H 12 N 3 ] + , 100). HRMS m / z calcd for C 10 H 12 N 3 174.1031; found 174.1035.

<< 실시예Example A-3> 1-벤질-3- A-3> 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 헥사플루오로포스페이트Hexafluorophosphate 염 (9c)의 합성 [ Synthesis of Salt (9c) [ BnmTrBnmTr ][] [ PFPF 66 ]]

5 mL 용량의 바이알에 <실시예 A-1-3>에서 제조한 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염(8)(0.600 g, 1.99 mmol)과 LiPF6 (Lithium hexafluorophosphate, 0.309g,1.99mmol), 증류수 2.0 mL를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 CH2Cl2으로 추출하였다. 유기층을 증류수로 씻어준 다음, 무수 MgSO4로 건조한 후, 감압 농축하여 1-벤질-3-메틸-1,2,3-트리아졸륨 헥사풀루오로포스페이트 염(9c)(0.606 g, 95%)를 노란색의 고체 상태로 얻었다. In a 5 mL vial, 1-benzyl-3-methyl-1,2,3-triazolium iodine salt ( 8 ) (0.600 g, 1.99 mmol) prepared in <Example A-1-3> and LiPF 6 (Lithium hexafluorophosphate, 0.309 g, 1.99 mmol) and 2.0 mL of distilled water were added thereto, followed by stirring at 40 ° C. for 24 hours. After cooling to room temperature, the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was washed with distilled water, dried over anhydrous MgSO 4, and then concentrated under reduced pressure to obtain 1-benzyl-3-methyl-1,2,3-triazolum hexafulurophosphate salt ( 9c ) (0.606 g, 95%) Was obtained as a yellow solid.

mp: 90.5-92.5 ℃. 1H-NMR (400 MHz, CDCl3): δ8.38 (s, 1H), 8.27 (s, 1H), 7.45 (m, 5H), 5.70 (s, 2H), 4.36 (s, 3H). 1H-NMR (400 MHz, DMSO-d 6): δ 8.96 (s, 1H), 8.84 (s, 1H), 7.47-7.43 (m, 5H), 5.88 (s, 2H), 4.30 (s, 3H). 13C-NMR (100 MHz, DMSO-d 6): δ133.0, 132.1, 130.8, 129.2, 129.1, 128.8, 56.0, 39.5. LRMS (FAB) m/z (rel int): (pos) 91 ([C7H7]+, 26), 174 ([C10H12N3]+, 100). HRMS m/z calcd for C10H12N3 174.1031; found 174.1036. Anal. Calcd for C10H12F6N3P: C, 37.63; H, 3.79; N, 13.16. Found: C, 37.80; H, 3.88; N, 13.31.mp: 90.5-92.5 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.38 (s, 1H), 8.27 (s, 1H), 7.45 (m, 5H), 5.70 (s, 2H), 4.36 (s, 3H). 1 H-NMR (400 MHz, DMSO- d 6 ): δ 8.96 (s, 1H), 8.84 (s, 1H), 7.47-7.43 (m, 5H), 5.88 (s, 2H), 4.30 (s, 3H ). 13 C-NMR (100 MHz, DMSO- d 6 ): δ 133.0, 132.1, 130.8, 129.2, 129.1, 128.8, 56.0, 39.5. LRMS (FAB) m / z (rel int): (pos) 91 ([C 7 H 7 ] + , 26), 174 ([C 10 H 12 N 3 ] + , 100). HRMS m / z calcd for C 10 H 12 N 3 174.1031; found 174.1036. Anal. Calcd for C 10 H 12 F 6 N 3 P: C, 37.63; H, 3.79; N, 13.16. Found: C, 37.80; H, 3.88; N, 13.31.

<< 실시예Example A-4> 1-벤질-3- A-4> 1-benzyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 테트라플루오로보레이트Tetrafluoroborate 염 (9d)의 합성 [ Synthesis of salts (9d) [ BnmTrBnmTr ][] [ BFBF 44 ]]

5 mL 용량의 바이알에 <실시예 A-1-3>에서 제조한 1-벤질-3-메틸-1,2,3-트리아졸륨 요오드염(8)(0.806 g, 2.68 mmol)과 AgBF4 (silver tetrafluoroborate, 0.521 g,2.68 mmol), 증류수 2.7 mL를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 CH2Cl2으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1-벤질-3-메틸-1,2,3-트리아졸륨 테트라플루오로보레이트 염(9d)(0.603 g, 62%)를 흰색의 고체 상태로 얻었다.Prepared in <Example A-1-3> in a 5 mL vial 1-benzyl-3-methyl-1,2,3-triazolium iodine salt ( 8 ) (0.806 g, 2.68 mmol) and AgBF 4 (silver tetrafluoroborate, 0.521 g, 2.68 mmol) were added thereto and 2.7 mL of distilled water was added at 40 ° C. Stir for 24 hours. After cooling to room temperature, the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to yield 1-benzyl-3-methyl-1,2,3-triazolium tetrafluoroborate salt ( 9d ) (0.603 g, 62%). Obtained in the solid state of.

mp: 74.3-76.3 ℃. 1H-NMR (400 MHz, CDCl3): δ 8.51 (s, 1H) ,8.49 (s, 1H), 7.47-7.44 (m, 2H), 7.40-7.38 (m, 3H), 5.70 (s, 2H), 4.30 (s, 3H). 13C-NMR (100 MHz, CDCl3): δ132.3, 131.7, 130.9, 130.1, 129.6, 129.5, 57.5, 40.4. LRMS (FAB) m/z (rel int): (pos) 91 ([C7H7]+, 39), 174 ([C10H12N3]+, 100). HRMS m/z calcd for C10H12N3 174.1031; found 174.1026. Anal. Calcd for C10H12BF4N3: C, 46.01; H, 4.63; N, 16.10. Found: C, 46.15; H, 4.57; N, 16.33.mp: 74.3-76.3 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.51 (s, 1H), 8.49 (s, 1H), 7.47-7.44 (m, 2H), 7.40-7.38 (m, 3H), 5.70 (s, 2H ), 4.30 (s, 3 H). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.3, 131.7, 130.9, 130.1, 129.6, 129.5, 57.5, 40.4. LRMS (FAB) m / z (rel int): (pos) 91 ([C 7 H 7 ] + , 39), 174 ([C 10 H 12 N 3 ] + , 100). HRMS m / z calcd for C 10 H 12 N 3 174.1031; found 174.1026. Anal. Calcd for C 10 H 12 BF 4 N 3 : C, 46.01; H, 4.63; N, 16.10. Found: C, 46.15; H, 4.57; N, 16.33.

<< 실시예Example B> 1-부틸-3- B> 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체의 합성  Synthesis of Ionic Liquids

<< 실시예Example B-1> 1-부틸-3- B-1> 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스( Vis ( 트리플루오로메틸술포Trifluoromethylsulfo 닐)Neil) 아미드염Amide salt (14a) 이온성 액체의 합성 [(14a) Synthesis of ionic liquids [ bmTrbmTr ][] [ NTfNTf 22 ]]

B-1-1 : 1-부틸-4-B-1-1: 1-butyl-4- 트리메틸실릴Trimethylsilyl -1,2,3--1,2,3- 트리아졸(11)과Triazole (11) 1-부틸-1,2,3- 1-butyl-1,2,3- 트리아Tria 졸(12)의 합성Synthesis of Sol

25 mL 용량의 바이알에 클로로부탄 (0.266 g, 2.87 mmol), 소듐 아자이드 (0.476 g, 7.32 mmol)를 DMF 3.7 mL에 녹여 80 ℃에서 20시간 동안 교반하였다. 20시간 후, 상온으로 식히고 트리메틸실릴아세틸렌 (0.359 g, 3.66 mmol), CuI (0.070 g, 0.366 mmol)를 가하였다. 이 혼합물을 40시간 동안 80 ℃에서 교반한 후, 상온으로 식히고 컬럼크로마토그래피 (Hexane/EtOAc = 1/5)로 정제하여 연한 노란색의 액체 상태의 1-부틸-4-트리메틸실릴-1,2,3-트리아졸 (11) (0.114 g, 16%)과 1-부틸-1,2,3-트리아졸 (12) (0.229 g, 64%)을 얻었다. In a 25 mL vial, chlorobutane (0.266 g, 2.87 mmol) and sodium azide (0.476 g, 7.32 mmol) were dissolved in 3.7 mL of DMF and stirred at 80 ° C for 20 h. After 20 h, cooled to room temperature and trimethylsilylacetylene (0.359 g, 3.66 mmol) and CuI (0.070 g, 0.366 mmol) were added. The mixture was stirred at 80 ° C. for 40 hours, then cooled to room temperature and purified by column chromatography (Hexane / EtOAc = 1/5) to give a pale yellow liquid 1-butyl-4-trimethylsilyl-1,2, 3-triazole ( 11 ) (0.114 g, 16%) and 1-butyl-1,2,3-triazole ( 12 ) (0.229 g, 64%) were obtained.

1-부틸-4- 트리메틸실릴 -1,2,3- 트리아졸 (11)- TLC: R f 0.42 (3:1 hexane/EtOAc). 1H-NMR (400 MHz, CDCl3): δ 7.49 (s, 1H), 4.38 (t, 2H, J = 7.4Hz), 1.89 (m, 2H), 1.37 (sextet, 2H, J = 7.4Hz), 0.96 (t, 3H, J = 7.4Hz), 0.33 (s, 9H). 13C-NMR (100 MHz, CDCl3): δ 146.7, 128.9, 49.7, 32.7, 20.0, 13.7, -0.9. LRMS (FAB) m/z (rel int): (pos) 198 ([M+H]+, 100). HRMS m/z calcd for C9H20N3Si 198.1427; found 198.1425. 1-Butyl-4- trimethylsilyl -1,2,3- triazole (11) -TLC: R f 0.42 (3: 1 hexane / EtOAc). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.49 (s, 1H), 4.38 (t, 2H, J = 7.4 Hz), 1.89 (m, 2H), 1.37 (sextet, 2H, J = 7.4 Hz) , 0.96 (t, 3H, J = 7.4 Hz), 0.33 (s, 9H). 13 C-NMR (100 MHz, CDCl 3 ): δ 146.7, 128.9, 49.7, 32.7, 20.0, 13.7, -0.9. LRMS (FAB) m / z (rel int): (pos) 198 ([M + H] + , 100). HRMS m / z calcd for C 9 H 20 N 3 Si 198.1427; found 198.1425.

1-부틸-1,2,3- 트리아졸 (12) - TLC: R f 0.16 (3:1=hexane/EtOAc(v/v). 1H-NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H, J = 7.4Hz), 1.90 (m, 2H), 1.36 (sextet, 2H, J = 7.4Hz), 0.96 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 134.0, 123.3, 50.1, 32.5, 19.9, 13.7. LRMS (FAB) m/z (rel int): (pos) 126 ([M+H]+, 86). HRMS m/z calcd for C6H12N3 126.1031; found 126.1032. 1-butyl-1,2,3- triazole (12) -TLC: R f 0.16 (3: 1 = hexane / EtOAc (v / v). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H, J = 7.4Hz), 1.90 (m, 2H ), 1.36 (sextet, 2H, J = 7.4Hz), 0.96 (t, 3H, J = 7.4Hz) 13 C-NMR (100 MHz, CDCl 3):. δ 134.0, 123.3, 50.1, 32.5, 19.9, 13.7.LRMS (FAB) m / z (rel int): (pos) 126 ([M + H] + , 86) .HRMS m / z calcd for C 6 H 12 N 3 126.1031; found 126.1032.

B-1-2 : 1-부틸-1,2,3-B-1-2: 1-butyl-1,2,3- 트리아졸(12)의Triazole (12) 합성 synthesis

둥근 바닥 플라스크에 <실시예 B-1-1>에서 제조한 1-부틸-4-트리메틸실릴-1,2,3-트리아졸(11)(2.15 g, 10.9 mmol)를 THF 10.9 mL에 녹여 교반하였다. 여기에 TBAF(1M THF 용액, 16.3 mL, 16.3 mmol)를 천천히 가하였다. 이를 상온에서 6시간 동안 교반한 후, 반응을 멈춘 뒤 용매를 감압 농축하고 컬럼크로마토그래피 (Hexane/EtOAc = 1/3(v/v))로 정제하여 1-부틸-1,2,3-트리아졸(12)(1.32 g, 97%)을 연한 노란색의 액체 상태로 얻었다. 1-butyl-4-trimethylsilyl-1,2,3-triazole ( 11 ) (2.15 g, 10.9 mmol) prepared in <Example B-1-1> was dissolved in THF 10.9 mL in a round bottom flask. It was. TBAF (1M THF solution, 16.3 mL, 16.3 mmol) was slowly added thereto. After stirring for 6 hours at room temperature, the reaction was stopped and the solvent was concentrated under reduced pressure, purified by column chromatography (Hexane / EtOAc = 1/3 (v / v)) to 1-butyl-1,2,3-tria Sol ( 12 ) (1.32 g, 97%) was obtained as a light yellow liquid.

TLC: R f 0.16 (3:1 hexane/EtOAc). 1H-NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H, J = 7.4Hz), 1.90 (m, 2H), 1.36 (sextet, 2H, J = 7.4Hz), 0.96 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 134.0, 123.3, 50.1, 32.5, 19.9, 13.7. LRMS (FAB) m/z (rel int): (pos) 126 ([M+H]+, 86). HRMS m/z calcd for C6H12N3 126.1031; found126.1032.TLC:R f 0.16 (3: 1 hexane / EtOAc).OneH-NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.53 (s, 1H), 4.40 (t, 2H,J= 7.4 Hz), 1.90 (m, 2H), 1.36 (sextet, 2H,J= 7.4 Hz), 0.96 (t, 3H,J= 7.4 Hz).13C-NMR (100 MHz, CDCl3): δ 134.0, 123.3, 50.1, 32.5, 19.9, 13.7. LRMS (FAB)m / z(rel int): (pos) 126 ([M + H]+, 86). HRMSm / zcalcd for C6H12N3 126.1031; found126.1032.

B-1-3 : 1-부틸-3-B-1-3: 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 요오드 염(13)의 합성 Synthesis of Iodine Salt (13) [ [ bmTrbmTr ][I]] [I]

5 mL 용량의 바이알에<실시예 B-1-2>에서 제조한 1-부틸-1,2,3-트리아졸(12)(3.52 g, 28.1 mmol)과 요오드화메틸(3.99 g, 28.1 mmol)을 넣고 80 ℃에서 24 시간 동안 교반하였다. 24시간 뒤, 상온으로 식히고 감압 농축하여 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드 염(13)(7.26 g, 97%)을 갈색의 액체 상태로 얻었다. In a 5-mL vial, 1-butyl-1,2,3-triazole ( 12 ) (3.52 g, 28.1 mmol) and methyl iodide (3.99 g, 28.1 mmol) prepared in <Example B-1-2> Was added and stirred at 80 ° C for 24 h. After 24 hours, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain 1-butyl-3-methyl-1,2,3-triazolium iodine salt ( 13 ) (7.26 g, 97%) as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 9.42 (s,1H), 9.38 (s,1H), 4.79 (t, 2H, J = 7.4Hz), 4.55 (s, 3H), 2.05 (m, 2H), 1.44 (sextet, 2H, J = 7.4Hz), 0.99 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 132.3, 131.4, 54.2, 41.3, 31.5, 19.4, 13.4. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]+, 100). HRMS m/z calcd for C7H14N3 140.1188; found 140.1186. Anal. Calcd for C7H14IN3: C, 31.48; H, 5.28; N, 15.73. Found: C, 31.51; H, 5.24; N, 15.65. 1 H-NMR (400 MHz, CDCl 3 ): δ 9.42 (s, 1H), 9.38 (s, 1H), 4.79 (t, 2H, J = 7.4 Hz), 4.55 (s, 3H), 2.05 (m, 2H), 1.44 (sextet, 2H, J = 7.4 Hz), 0.99 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.3, 131.4, 54.2, 41.3, 31.5, 19.4, 13.4. LRMS (FAB) m / z (rel int): (pos) 140 ([C 7 H 14 N 3 ] + , 100). HRMS m / z calcd for C 7 H 14 N 3 140.1188; found 140.1186. Anal. Calcd for C 7 H 14 IN 3 : C, 31.48; H, 5. 28; N, 15.73. Found: C, 31.51; H, 5. 24; N, 15.65.

B-1-4 : 1-부틸-3-B-1-4: 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스(트리플루오로메틸술포닐)아미Bis (trifluoromethylsulfonyl) ami 드 염(14a)의 합성Synthesis of De Salt (14a)

5 mL 용량의 바이알에 <실시예 B-1-3>에서 제조한 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드 염(13)(43.1 mg, 0.161 mmol)과 LiNTf2 (46.3 mg, 0.161 mmol), 증류수 (0.8 mL)를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 CH2Cl2으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1-부틸-3-메틸-1,2,3-트리아졸륨 비스(트리플루오로메틸술포닐)아미드 염(14a)(60.9 mg, 90%)을 갈색의 액체 상태로 얻었다.In a 5-mL vial, 1-butyl-3-methyl-1,2,3-triazolium iodine salt ( 13 ) (43.1 mg, 0.161 mmol) and LiNTf 2 prepared in <Example B-1-3> (46.3 mg, 0.161 mmol) and distilled water (0.8 mL) were added and stirred at 40 ° C for 24 hours. After cooling to room temperature, the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to obtain 1-butyl-3-methyl-1,2,3-triazolium bis (trifluoromethylsulfonyl) amide salt ( 14a ) (60.9 mg , 90%) was obtained as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 8.51 (s, 1H), 8.45 (s, 1H), 4.60 (t, 2H, J = 7.4Hz), 4.39 (s, 3H), 2.03 (m, 2H), 1.43 (sextet, 2H, J = 7.4Hz), 1.01 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 131.5, 130.5, 119.9 (q, J CF = 319.1Hz), 54.2, 40.4, 31.2, 19.4, 13.2. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]+, 100). HRMS m/z calcd for C7H14N3 140.1188; found 140.1188. Anal. Calcd for C9H14F6N4O4S2: C, 25.72; H, 3.36; N, 13.33; S, 15.26. Found: C, 25.98; H, 3.27; N, 13.26; S, 15.36. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.51 (s, 1H), 8.45 (s, 1H), 4.60 (t, 2H, J = 7.4 Hz), 4.39 (s, 3H), 2.03 (m, 2H), 1.43 (sextet, 2H, J = 7.4 Hz), 1.01 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 131.5, 130.5, 119.9 (q, J CF = 319.1 Hz), 54.2, 40.4, 31.2, 19.4, 13.2. LRMS (FAB) m / z (rel int): (pos) 140 ([C 7 H 14 N 3 ] + , 100). HRMS m / z calcd for C 7 H 14 N 3 140.1188; found 140.1188. Anal. Calcd for C 9 H 14 F 6 N 4 O 4 S 2 : C, 25.72; H, 3. 36; N, 13.33; S, 15.26. Found: C, 25.98; H, 3. 27; N, 13.26; S, 15.36.

<< 실시예Example B-2> 1-부틸-3- B-2> 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아조륨Triazium 트리플루오로메탄설포네이트Trifluoromethanesulfonate 염(14b)의 합성 [ Synthesis of Salt (14b) [ bmTrbmTr ][] [ OTfOTf ]]

5 mL 용량의 바이알에<실시예 B-1-3>에서 제조한 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드 염(13)(0.234 g, 0.874 mmol)과 KOTf (0.168 g, 0.874 mmol), 증류수(1.3 mL)를 넣고 40 ℃에서 24시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1-부틸-3-메틸-1,2,3-트리아조륨 트리플루오로메탄설포네이트 염(14b)(0.213 g, 84%)을 갈색의 액체 상태로 얻었다. In a 5-mL vial, 1-butyl-3-methyl-1,2,3-triazolium iodine salt ( 13) (0.234 g, 0.874 mmol) and KOTf (0.168) prepared in <Example B-1-3> g, 0.874 mmol) and distilled water (1.3 mL) were added and stirred at 40 ° C. for 24 hours. After cooling to room temperature, the aqueous layer is washed with IPA / CHCl 3 Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4, and then concentrated under reduced pressure to obtain 1-butyl-3-methyl-1,2,3-triazorium trifluoromethanesulfonate salt ( 14b ) (0.213 g, 84%) Was obtained in a brown liquid state.

1H-NMR (400 MHz, CDCl3): δ 9.01 (s, 1H), 8.92 (s, 1H), 4.66 (t, 2H, J = 7.4Hz), 4.44 (s, 3H), 2.03 (m, 2H), 1.42 (sextet, 2H, J = 7.4Hz), 1.00 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 132.0, 131.1, 120.6 (q, J CF = 318.2Hz), 54.0, 40.6, 31.3, 19.4, 13.3. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]+, 100). HRMS m/z calcd for C7H14N3 140.1188; found 140.1186. Anal. Calcd for C8H14F3N3O3S: C, 33.22; H, 4.88; N, 14.53. Found: C, 33.45; H, 5.05; N,14.14. 1 H-NMR (400 MHz, CDCl 3 ): δ 9.01 (s, 1H), 8.92 (s, 1H), 4.66 (t, 2H, J = 7.4 Hz), 4.44 (s, 3H), 2.03 (m, 2H), 1.42 (sextet, 2H, J = 7.4 Hz), 1.00 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.0, 131.1, 120.6 (q, J CF = 318.2 Hz), 54.0, 40.6, 31.3, 19.4, 13.3. LRMS (FAB) m / z (rel int): (pos) 140 ([C 7 H 14 N 3 ] + , 100). HRMS m / z calcd for C 7 H 14 N 3 140.1188; found 140.1186. Anal. Calcd for C 8 H 14 F 3 N 3 O 3 S: C, 33.22; H, 4.88; N, 14.53. Found: C, 33.45; H, 5.05; N, 14.14.

<< 실시예Example B-3> 1-부틸-3- B-3> 1-butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 헥사플루오로포스페이트Hexafluorophosphate 염(14c)의 합성 [ Synthesis of Salt (14c) [ bmTrbmTr ][] [ PFPF 66 ]]

5 mL 용량의 바이알에<실시예 B-1-3>에서 제조한 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드 염(13)(0.198 g, 0.742 mmol)과 LiPF6 (0.115g, 0.742mmol), 증류수 (1.5 mL)를 넣고 40 ℃에서 11시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA/CHCl3(1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음, 무수 MgSO4로 건조한 후, 감압 농축하여 1-부틸-3-메틸-1,2,3-트리아졸륨 헥사플루오로포스페이트 염(14c)(0.176 g, 83%)을 갈색의 액체 상태로 얻었다. 이를 참고문헌에 따라 탈색하였다(M. J. Earle, C. M. Gordon, N. J. Plechkova, K. R. Seddon and T. Welton, Anal . Chem ., 2007, 79, 758).In a 5 mL vial, 1-butyl-3-methyl-1,2,3-triazolium iodine salt ( 13 ) (0.198 g, 0.742 mmol) prepared in <Example B-1-3> and LiPF 6 (0.115 g, 0.742 mmol) and distilled water (1.5 mL) were added thereto, and the resulting mixture was stirred at 40 ° C. for 11 hours. After cooling to room temperature, the water layer was extracted with IPA / CHCl 3 (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to obtain 1-butyl-3-methyl-1,2,3-triazolium hexafluorophosphate salt ( 14c ) (0.176 g, 83%). Obtained as a brown liquid. This was bleached according to the reference (MJ Earle, CM Gordon, NJ Plechkova, KR Seddon and T. Welton, Anal . Chem . , 2007, 79, 758).

1H-NMR (400 MHz, CDCl3): δ 8.47 (s, 1H), 8.44 (s, 1H), 4.58 (t, 2H, J = 7.4Hz), 4.36 (s, 3H), 2.00 (m, 2H), 1.41 (sextet, 2H, J = 7.4Hz), 0.98 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 131.8, 130.7, 54.1, 40.4, 31.3, 19.5, 13.4. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]+, 100). HRMS m/z calcd for C7H14N3 140.1188; found 140.1186. Anal. Calcd for C7H14F6N3P: C, 29.48; H, 4.95; N, 14.74. Found: C, 29.61; H, 4.95; N, 14.82. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.47 (s, 1H), 8.44 (s, 1H), 4.58 (t, 2H, J = 7.4 Hz), 4.36 (s, 3H), 2.00 (m, 2H), 1.41 (sextet, 2H, J = 7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 131.8, 130.7, 54.1, 40.4, 31.3, 19.5, 13.4. LRMS (FAB) m / z (rel int): (pos) 140 ([C 7 H 14 N 3 ] + , 100). HRMS m / z calcd for C 7 H 14 N 3 140.1188; found 140.1186. Anal. Calcd for C 7 H 14 F 6 N 3 P: C, 29.48; H, 4.95; N, 14.74. Found: C, 29.61; H, 4.95; N, 14.82.

<< 실시예Example B-4> 1-부틸-3- B-4> 1-Butyl-3- 메틸methyl -1,2,3--1,2,3- 트리아졸륨Triazium 테트라플루오로보레이트Tetrafluoroborate 염 (14d)의 합성 [ Synthesis of Salt (14d) [ bmTrbmTr ][] [ BFBF 44 ]]

5 mL 용량의 바이알에<실시예 B-1-3>에서 제조한 1-부틸-3-메틸-1,2,3-트리아졸륨 요오드 염(13)(99.6 mg, 0.373 mmol)과 AgBF4 (73.3mg, 0.373mmol), 증류수 (0.8 mL)를 넣고 40 ℃에서 17시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA(이소프로필알코올)/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1-부틸-3-메틸-1,2,3-트리아졸륨 테트라플루오로보레이트 염(14d)(62.6 mg, 74%)을 연한 노란색의 액체 상태로 얻었다. In a 5-mL vial, 1-butyl-3-methyl-1,2,3-triazolium iodine salt ( 13 ) (99.6 mg, 0.373 mmol) and AgBF 4 prepared in <Example B-1-3> (73.3mg, 0.373mmol) and distilled water (0.8 mL) were added thereto, and the result was stirred for 17 hours at 40 ° C. After cooling to room temperature, the aqueous layer was washed with IPA (isopropyl alcohol) / CHCl 3. Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to give 1-butyl-3-methyl-1,2,3-triazolium tetrafluoroborate salt ( 14d ) (62.6 mg, 74%). Obtained as a yellow liquid.

1H-NMR (400 MHz, CDCl3): δ 8.60 (s, 1H), 8.46 (s, 1H), 4.59 (t, 2H, J = 7.4Hz), 4.37 (s, 3H), 2.00 (m, 2H), 1.42 (sextet, 2H, J = 7.4Hz), 0.98 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 132.0, 130.9, 53.9, 40.2, 31.3, 19.5, 13.4. LRMS (FAB) m/z (rel int): (pos) 140 ([C7H14N3]+, 100). HRMS m/z calcd for C7H14N3 140.1188; found 140.1182. Anal. Calcd for C7H14BF4N3: C, 37.04; H, 6.22; N, 18.51. Found: C, 37.49; H, 6.29; N, 18.01. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.60 (s, 1H), 8.46 (s, 1H), 4.59 (t, 2H, J = 7.4 Hz), 4.37 (s, 3H), 2.00 (m, 2H), 1.42 (sextet, 2H, J = 7.4 Hz), 0.98 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 132.0, 130.9, 53.9, 40.2, 31.3, 19.5, 13.4. LRMS (FAB) m / z (rel int): (pos) 140 ([C 7 H 14 N 3 ] + , 100). HRMS m / z calcd for C 7 H 14 N 3 140.1188; found 140.1182. Anal. Calcd for C 7 H 14 BF 4 N 3 : C, 37.04; H, 6. 22; N, 18.51. Found: C, 37.49; H, 6. 29; N, 18.01.

<< 실시예Example C> 1,3- C> 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체 합성 Ionic Liquid Synthesis

<< 실시예Example C-1> 1,3- C-1> 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스(트리플루오로메틸술포닐)아Bis (trifluoromethylsulfonyl) a 미드 염(17a)의 합성 [Synthesis of Mid Salt (17a) [ dbTrdbTr ][] [ NTfNTf 22 ]]

C-1-1 : 1,3-C-1-1: 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 요오드염Iodine salt (16)의 합성 Synthesis of 16

50 mL 둥근 바닥 플라스크에 NaH (0.157 g, 6.21 mmol)와 CH3CN (5 mL)를 넣고 0 ℃에서 교반한다. 30분 후, 1H-1,2,3-트리아졸 (0.358g,5.18mmol)를 가한다. 20분 후, 부틸아이오다이드 (4.81 g, 25.9 mmol)를 가하고, 이를 80 ℃에서 19시간 동안 교반하였다. 상온으로 식힌 후, 컬럼크로마토그래피 (Hexane/EtOAc = 1/1 (v/v)→ CH2Cl2/MeOH=4/1(v/v))로 정제하여 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(1.21 g, 75%)을 갈색의 액체 상태로 얻었다. Into a 50 mL round bottom flask, NaH (0.157 g, 6.21 mmol) and CH 3 CN (5 mL) were added and stirred at 0 ° C. After 30 minutes, 1 H -1,2,3-triazole (0.358 g, 5.18 mmol) is added. After 20 minutes, butyl iodide (4.81 g, 25.9 mmol) was added and stirred at 80 ° C for 19 h. After cooling to room temperature, the mixture was purified by column chromatography (Hexane / EtOAc = 1/1 (v / v) → CH 2 Cl 2 / MeOH = 4/1 (v / v)) to give 1,3-dibutyl-1, 2,3-triazolium iodine salt ( 16 ) (1.21 g, 75%) was obtained as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 9.44 (s, 2H), 4.77 (t, 4H, J = 7.4Hz), 2.05 (m, 4H), 1.43 (sextet, 4H, J = 7.4Hz), 1.00 (t, 6H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 131.6, 54.3, 31.6, 19.5, 13.5. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]+, 100). HRMS m/z calcd for C10H20N3 182.1657; found 182.1651. Anal. Calcd for C10H20IN3: C, 38.85; H, 6.52; N, 13.59. Found: C, 39.32; H, 6.71; N,12.94. 1 H-NMR (400 MHz, CDCl 3 ): δ 9.44 (s, 2H), 4.77 (t, 4H, J = 7.4 Hz), 2.05 (m, 4H), 1.43 (sextet, 4H, J = 7.4 Hz) , 1.00 (t, 6H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 131.6, 54.3, 31.6, 19.5, 13.5. LRMS (FAB) m / z (rel int): (pos) 182 ([C 10 H 20 N 3 ] + , 100). HRMS m / z calcd for C 10 H 20 N 3 182.1657; found 182.1651. Anal. Calcd for C 10 H 20 IN 3 : C, 38.85; H, 6.52; N, 13.59. Found: C, 39.32; H, 6. 71; N, 12.94.

C-1-1' : 1,3-C-1-1 ': 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 요오드염Iodine salt (16)의 합성 Synthesis of 16 [ [ dbTrdbTr ][I]] [I]

<실시예 B-1-2>에서 제조한 부틸트리아졸 12를 출발 물질로 하여 5 mL 용량의 바이알에 부틸트리아졸(12)(36.5 mg, 0.292 mmol)과 부틸아이오다이드(53.7 mg, 0.292 mmol)을 넣고 80 ℃에서 14.5 시간 동안 교반하였다. 그 후, 상온으로 식히고 감압 농축하여 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(86 mg, 95%)을 갈색의 액체 상태로 얻었다.Butyltriazole ( 12 ) (36.5 mg, 0.292 mmol) and butyl iodide (53.7 mg, 0.292) in 5 mL vials using butyltriazole 12 prepared in Example B-1-2 as a starting material. mmol) and stirred at 80 ° C for 14.5 h. Thereafter, the mixture was cooled to room temperature and concentrated under reduced pressure to obtain 1,3-dibutyl-1,2,3-triazolium iodine salt ( 16 ) (86 mg, 95%) as a brown liquid.

C-1-2 : 1,3-C-1-2: 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 비스(트리플루오로메틸술포닐)아미드Bis (trifluoromethylsulfonyl) amide 염(17a)의 합성 Synthesis of Salt (17a)

5 mL 용량의 바이알에 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(37 mg, 0.120 mmol)과 LiNTf2 (34.4 mg, 0.120 mmol), 증류수 (0.6 mL)를 넣고 40 ℃에서 15시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA(이소프로필알코올)/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음, 무수 MgSO4로 건조한 후, 감압 농축하여 1,3-디부틸-1,2,3-트리아졸륨 비스(트리플루오로메틸술포닐)아미드 염(17a)(55.1 mg, 100%)을 갈색의 액체 상태로 얻었다. In a 5 mL vial, 1,3-dibutyl-1,2,3-triazolium iodine salt ( 16 ) (37 mg, 0.120 mmol) and LiNTf 2 (34.4 mg, 0.120 mmol) and distilled water (0.6 mL) were added and stirred at 40 ° C. for 15 hours. After cooling to room temperature, the aqueous layer was washed with IPA (isopropyl alcohol) / CHCl 3. Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4, and then concentrated under reduced pressure to obtain 1,3-dibutyl-1,2,3-triazolium bis (trifluoromethylsulfonyl) amide salt ( 17a ) (55.1 mg , 100%) was obtained as a brown liquid.

1H-NMR (400 MHz, CDCl3): δ 8.52 (s, 2H), 4.61 (t, 4H, J = 7.4Hz), 2.03 (m, 4H), 1.42 (sextet, 4H, J = 7.4Hz), 1.00 (t, 6H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 130.9, 119.9 (q, J CF = 319.1Hz), 54.3, 31.3, 19.5, 13.3. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]+, 100). HRMS m/z calcd for C10H20N3 182.1657; found 182.1661. Anal. Calcd for C12H20F6N4O4S2: C, 31.17; H, 4.36; N, 12.12; S, 13.87. Found: C, 31.55; H, 4.35; N, 12.07; S, 13.80. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.52 (s, 2H), 4.61 (t, 4H, J = 7.4 Hz), 2.03 (m, 4H), 1.42 (sextet, 4H, J = 7.4 Hz) , 1.00 (t, 6H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 130.9, 119.9 (q, J CF = 319.1 Hz), 54.3, 31.3, 19.5, 13.3. LRMS (FAB) m / z (rel int): (pos) 182 ([C 10 H 20 N 3 ] + , 100). HRMS m / z calcd for C 10 H 20 N 3 182.1657; found 182.1661. Anal. Calcd for C 12 H 20 F 6 N 4 O 4 S 2 : C, 31.17; H, 4. 36; N, 12.12; S, 13.87. Found: C, 31.55; H, 4. 35; N, 12.07; S, 13.80.

<< 실시예Example C-2>1,3- C-2> 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 트리플루오로메탄설포네이트Trifluoromethanesulfonate 염(17b)의 합성 [ Synthesis of Salt (17b) [ dbTrdbTr ][] [ OTfOTf ]]

5 mL 용량의 바이알에 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(0.328 g, 1.06 mmol)과 KOTf (0.204 g, 1.06 mmol), 증류수 (1.5 mL)를 넣고 40 ℃에서 11시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA(이소프로필알코올)/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음, 무수 MgSO4로 건조한 후, 감압 농축하여 1,3-디부틸-1,2,3-트리아졸륨 트리플루오로메탄설포네이트 염(17b)(0.331 g, 94%)을 갈색의 액체 상태로 얻었다.To a 5 mL vial, add 1,3-dibutyl-1,2,3-triazolium iodine salt ( 16 ) (0.328 g, 1.06 mmol), KOTf (0.204 g, 1.06 mmol), and distilled water (1.5 mL). Stir at 40 ° C. for 11 hours. After cooling to room temperature, the aqueous layer was washed with IPA (isopropyl alcohol) / CHCl 3. Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to obtain 1,3-dibutyl-1,2,3-triazolium trifluoromethanesulfonate salt ( 17b ) (0.331 g, 94%) Was obtained in a brown liquid state.

1H-NMR (400 MHz, CDCl3): δ 8.99 (s, 2H), 4.68 (t, 4H, J = 7.4Hz), 2.02 (m, 4H), 1.41 (sextet, 4H, J = 7.4Hz), 0.99 (t, 6H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 131.0, 120.6 (q, J CF = 318.2Hz), 53.9, 31.3, 19.3, 13.2. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]+, 100). HRMS m/z calcd for C10H20N3 182.1657; found 182.1661. Anal. Calcd for C11H20F3N3O3S: C, 39.87; H, 6.08; N, 12.68. Found: C, 39.89; H, 6.28; N, 13.08. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.99 (s, 2H), 4.68 (t, 4H, J = 7.4 Hz), 2.02 (m, 4H), 1.41 (sextet, 4H, J = 7.4 Hz) , 0.99 (t, 6H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 131.0, 120.6 (q, J CF = 318.2 Hz), 53.9, 31.3, 19.3, 13.2. LRMS (FAB) m / z (rel int): (pos) 182 ([C 10 H 20 N 3 ] + , 100). HRMS m / z calcd for C 10 H 20 N 3 182.1657; found 182.1661. Anal. Calcd for C 11 H 20 F 3 N 3 O 3 S: C, 39.87; H, 6.08; N, 12.68. Found: C, 39.89; H, 6. 28; N, 13.08.

<< 실시예Example C-3> 1,3- C-3> 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 헥사플루오로포스페이트Hexafluorophosphate 염 (17c)의 합성 [ Synthesis of Salt (17c) [ dbTrdbTr ][] [ PFPF 66 ]]

5 mL 용량의 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(0.362 g, 1.17 mmol)과 LiPF6 (0.182g,1.17mmol), 증류수 (1.7 mL)를 넣고 40 ℃에서 22시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA(이소프로필알코올)/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1,3-디부틸-1,2,3-트리아졸륨 헥사플루오로포스페이트 염(17c)(0.359 g, 94%)을 갈색의 액체 상태로 얻었다. 5 mL volume of 1,3-dibutyl-1,2,3-triazolium iodine salt ( 16 ) (0.362 g, 1.17 mmol) with LiPF 6 (0.182 g, 1.17 mmol) and distilled water (1.7 mL) were added thereto, and the mixture was stirred at 40 ° C. for 22 hours. After cooling to room temperature, the aqueous layer was washed with IPA (isopropyl alcohol) / CHCl 3. Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to give 1,3-dibutyl-1,2,3-triazolium hexafluorophosphate salt ( 17c ) (0.359 g, 94%) in brown color. Obtained in liquid state.

1H-NMR (400 MHz, CDCl3): δ 8.51 (s, 2H), 4.61 (t, 4H, J = 7.4Hz), 2.01 (m, 4H), 1.41 (sextet, 4H, J = 7.4Hz), 0.99 (t, 6H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 130.9, 54.2, 31.4, 19.5, 13.4. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]+, 100). HRMS m/z calcd for C10H20N3 182.1657; found 182.1661. Anal. Calcd for C10H20F6N3P: C, 36.70; H, 6.16; N, 12.84. Found: C, 36.68; H, 6.19; N, 12.90. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.51 (s, 2H), 4.61 (t, 4H, J = 7.4 Hz), 2.01 (m, 4H), 1.41 (sextet, 4H, J = 7.4 Hz) , 0.99 (t, 6H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 130.9, 54.2, 31.4, 19.5, 13.4. LRMS (FAB) m / z (rel int): (pos) 182 ([C 10 H 20 N 3 ] + , 100). HRMS m / z calcd for C 10 H 20 N 3 182.1657; found 182.1661. Anal. Calcd for C 10 H 20 F 6 N 3 P: C, 36.70; H, 6. 16; N, 12.84. Found: C, 36.68; H, 6. 19; N, 12.90.

<< 실시예Example C-4> 1,3- C-4> 1,3- 디부틸Dibutyl -1,2,3--1,2,3- 트리아졸륨Triazium 테트라플루오로보레이트Tetrafluoroborate 염 (17d)의 합성 [ Synthesis of salts (17d) [ dbTrdbTr ][] [ BFBF 44 ]]

5 mL 용량의 바이알에 1,3-디부틸-1,2,3-트리아졸륨 요오드염(16)(0.279 g, 0.903 mmol)과 AgBF4 (0.178 g,0.903 mmol), 증류수 (1.3 mL)를 넣고 40 ℃에서 20시간 동안 교반하였다. 그 뒤, 상온으로 식히고 물층을 IPA(이소프로필알코올)/CHCl3 (1/4(v/v))으로 추출하였다. 유기층을 증류수로 씻어준 다음 무수 MgSO4로 건조한 후, 감압 농축하여 1,3-디부틸-1,2,3-트리아졸륨 테트라플루오로보레이트 염(17d)(0.217 g, 89%)을 노란색의 액체 상태로 얻었다. In a 5 mL vial 1,3-dibutyl-1,2,3-triazolium iodine salt ( 16 ) (0.279 g, 0.903 mmol) and AgBF 4 (0.178 g, 0.903 mmol) and distilled water (1.3 mL) were added and stirred at 40 ° C for 20 hours. After cooling to room temperature, the aqueous layer was washed with IPA (isopropyl alcohol) / CHCl 3. Extracted with (1/4 (v / v)). The organic layer was washed with distilled water, dried over anhydrous MgSO 4 , and concentrated under reduced pressure to give 1,3-dibutyl-1,2,3-triazolium tetrafluoroborate salt ( 17d ) (0.217 g, 89%) in yellow color. Obtained in liquid state.

1H-NMR (400 MHz, CDCl3): δ 8.62 (s, 2H), 4.62 (t, 4H, J = 7.4Hz), 2.00 (m, 4H), 1.40 (sextet, 2H, J = 7.4Hz), 0.98 (t, 3H, J = 7.4Hz). 13C-NMR (100 MHz, CDCl3): δ 131.1, 54.0, 31.4, 19.5, 13.4. LRMS (FAB) m/z (rel int): (pos) 182 ([C10H20N3]+, 100). HRMS m/z calcd for C10H20N3 182.1657; found 182.1657. Anal. Calcd for C10H20BF4N3: C, 44.63; H, 7.49; N, 15.62. Found: C, 44.66; H, 7.41; N, 15.51. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.62 (s, 2H), 4.62 (t, 4H, J = 7.4 Hz), 2.00 (m, 4H), 1.40 (sextet, 2H, J = 7.4 Hz) , 0.98 (t, 3H, J = 7.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 131.1, 54.0, 31.4, 19.5, 13.4. LRMS (FAB) m / z (rel int): (pos) 182 ([C 10 H 20 N 3 ] + , 100). HRMS m / z calcd for C 10 H 20 N 3 182.1657; found 182.1657. Anal. Calcd for C 10 H 20 BF 4 N 3 : C, 44.63; H, 7. 49; N, 15.62. Found: C, 44.66; H, 7.41; N, 15.51.

<< 실험예Experimental Example 1> 다양한 1,3- 1> various 1,3- 디알킬Dialkyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체에서 p- P- in ionic liquids 클로로Chloro 벤즈알데히드와 Benzaldehyde and 메틸methyl 아크릴레이트의Acrylate BaylisBaylis -- HillmanHillman 반응 수율 향상 확인  Confirmation of reaction yield improvement

Baylis-Hillman 반응에서 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체의 반응성을 비교하기 위해, 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체 (0.1 mL) 존재 하에서 p-클로로벤즈알데히드 (p-chlorobenzaldehyde, 1 mmol), 메틸 아크릴레이트 (methylacrylate, 2 mmol), 그리고 DABCO(2 mmol)의 Baylis-Hillman 반응을 시행하였다. 모든 반응은 상온에서 24 시간 동안 진행하였으며, 생성된 18a는 컬럼크로마토 그래피를 통하여 정제하였다. 상온에서 고체 염인 [BnmTr][I](8), [BnmTr][PF6] (9c),그리고 [BnmTr][BF4] (9d)를 제외한 상온 이온성 액체로 반응을 진행하였다. 그 결과는 하기 [표 1]과 같다. To compare the reactivity of 1,3-dialkyl-1,2,3-triazolium ionic liquids in the Baylis-Hillman reaction, 1,3-dialkyl-1,2,3-triazolium ionic liquids (0.1 Baylis-Hillman reaction of p-chlorobenzaldehyde (p-chlorobenzaldehyde, 1 mmol), methyl acrylate (methylacrylate, 2 mmol), and DABCO (2 mmol) was carried out in the presence of 2 mL). All reactions proceeded at room temperature for 24 hours, and the resulting 18a was purified by column chromatography. At room temperature, the reaction proceeded with a room temperature ionic liquid except for [BnmTr] [I] ( 8 ), [BnmTr] [PF 6 ] ( 9c ), and [BnmTr] [BF 4 ] ( 9d ). The results are shown in the following [Table 1].

[표 1] 다양한 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체에서 p-클로로벤즈알데히드 (p-chloro benzaldehyde)와 메틸 아크릴레이트(methylacrylate)의 BaylisHillman 반응 a Table 1, various 1,3-dialkyl-1,2,3-triazolium ionic p- chlorobenzaldehyde in a liquid (p -chloro benzaldehyde) and BaylisHillman reaction of methyl acrylate (methylacrylate) a

Figure 112009075196023-pat00016
Figure 112009075196023-pat00016

상기 [표 1]에서 나타낸바와 같이, 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체는 Baylis-Hillman 반응에서 좋은 반응 속도와 수득율을 보였다. 특히, [bmTr][PF6](14c)와 [dbTr][NTf2](17a)(entries 6 and 9)를 이용한 Baylis-Hillman 반응의 경우 90%가 넘는 수득율 결과를 보였다. As shown in Table 1, the 1,3-dialkyl-1,2,3-triazolium ionic liquid showed good reaction rate and yield in the Baylis-Hillman reaction. In particular, Baylis-Hillman reaction using [bmTr] [PF 6 ] ( 14c ) and [dbTr] [NTf 2 ] ( 17a ) (entries 6 and 9) yielded over 90% yield.

또한, 기존에 널리 사용되는 이미다졸륨 이온성 액체인 [bmim][PF6]와 본 발명에서 개발한 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체의 비교에 초점을 두어, 같은 반응 조건에서 Baylis-Hillman 반응을 확인하였다 (entry 13). 예상과 같이 [BnmTr][NTf2] (9a), [bmTr][I] (13), 그리고 [bmTr][OTf] (14b)를 제외한 대부분의 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체는 이미다졸륨 이온성 액체인 [bmim][PF6]보다 좋은 수율을 보였다(74-96% vs 67%). 특히, 같은 PF6 음이온을 가지는 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체, [bmTr][PF6](14c)과 [dbTr][PF6](17c)(entries 6 and 11)는 [bmim][PF6]보다 더 높은 수율을 보였다(96% and 80% vs 67%). 이로 미루어 볼 때, 염기성 반응 조건에서 [bmim] 양이온의 C-2 수소의 탈수소(deprotonation)로 생성되는 문제점은 본 발명의 [bmTr] 또는 [dbTr]를 이용한 이온성 액체로 해결할 수 있다.In addition, we focus on comparing [bmim] [PF 6 ], a widely used imidazolium ionic liquid, with the 1,3-dialkyl-1,2,3-triazolium ionic liquid developed in the present invention. In addition, the Baylis-Hillman reaction was confirmed under the same reaction conditions (entry 13). As expected, most 1,3-dialkyl-1,2,3 except for [BnmTr] [NTf 2 ] ( 9a ), [bmTr] [I] ( 13 ), and [bmTr] [OTf] ( 14b ). The triazolium ionic liquid showed a better yield than imidazolium ionic liquid [bmim] [PF 6 ] (74-96% vs 67%). In particular, 1,3-dialkyl-1,2,3-triazolium ionic liquids having the same PF 6 anion, [bmTr] [PF 6 ] ( 14c ) and [dbTr] [PF 6 ] ( 17c ) (entries 6 and 11) showed higher yields than [bmim] [PF 6 ] (96% and 80% vs 67%). In view of this, the problem of deprotonation of C-2 hydrogen of [bmim] cation under basic reaction conditions can be solved with an ionic liquid using [bmTr] or [dbTr] of the present invention.

<< 실험예Experimental Example 2> 1,3- 2> 1,3- 디알킬Dialkyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체에서 알데히드와  With aldehydes in ionic liquids 메틸methyl 아크릴레이트의  Acrylate BaylisBaylis -- HillmanHillman 반응 실험방법 Reaction Experiment Method

실험예 1의 결과를 바탕으로 Baylis-Hillman 반응을 시행하기 위한 최선의 ionic liquid로 [bmTr][PF6](14c)를 선택하였다. [bmTr][PF6](14c)를 이용하여 지방족 (aliphatic), 방향족(aromatic), 그리고 알파,베타-불포화 (α,β-unsaturated) 알데히드와 같은 다양한 알데히드를 출발 물질로 하여 Baylis-Hillman 반응을 시행하였다. 즉, 1 mL 용량의 둥근 바닥 플라스크에 알데히드(1.00 mmol)와 DABCO (1,4-diazabicyclo[2.2.2]octane, 0.230 g, 2.01 mmol)를 Ar-degassed [bmTr][PF6] 0.1 mL에 녹였다. 메틸 아크릴레이트 (0.173 g, 2.01 mmol)을 가한 뒤, 상온에서 교반하였다. 반응이 종료된 후, 컬럼크로마토 그래피로 정제하여 원하는 화합물 18b-18k을 얻었다. 그 결과는 하기 [표 2]와 같다. Of Experimental Example 1 Based on the results, [bmTr] [PF 6 ] ( 14c ) was chosen as the best ionic liquid for the Baylis-Hillman reaction. Baylis-Hillman reaction using various aldehydes such as aliphatic, aromatic, and alpha, beta-unsaturated aldehydes with [bmTr] [PF 6 ] ( 14c ) Was implemented. In a 1 mL round bottom flask, aldehyde (1.00 mmol) and DABCO (1,4-diazabicyclo [2.2.2] octane, 0.230 g, 2.01 mmol) were added to 0.1 mL of Ar-degassed [bmTr] [PF 6 ]. Melted. Methyl acrylate (0.173 g, 2.01 mmol) was added and stirred at room temperature. After the reaction was completed, purification by column chromatography gave the desired compound 18b-18k . The results are shown in the following [Table 2].

[표 2] [bmTr][PF6] a 이온성 액체에서 다양한 알데히드와 메틸 아크릴레이트(methyl acrylate)의 BaylisHillman 반응[Table 2] [bmTr] [PF 6 ] a ionic BaylisHillman reaction of various aldehydes and methyl acrylate (methyl acrylate) in the liquid

Figure 112009075196023-pat00017
Figure 112009075196023-pat00017

상기 [표 2]에서 나타난 바와 같이, p-니트로페닐(p-nitrophenyl), 4-피리딜(4-pyridyl), 또는 p-트리플루오로에틸페닐기(p-trifluoromethylphenyl group)(entries 1, 4, and 10)를 가지는 기질의 반응이 빠르게 진행되었다. 위의 결과로 볼 때, p-니트로벤즈알데히드(p-nitrobenzaldehyde)의 니트로기(nitro group)와 4-피리딘카복시알데히드(4-pyridine carboxaldehyde)의 피리딘 안의 질소에 의한 전자 끌기 공명효과(electron-withdrawing resonance effect)가 Baylis-Hillman 반응을 가속화하는 것으로 보인다. 반면, 지방족 알데히드(aliphatic aldehyde)(entry 8)와 전자공여 작용기 (electron-donating groups)를 가지는 방향족 알데히드(aromatic aldehydes)(entries 6 and 9)의 경우, 상대적으로 반응 속도가 느리고, 중간 정도의 수율로 반응이 진행되었다. As shown in Table 2, p-nitrophenyl, 4-pyridyl, or p-trifluoroethylphenyl group (entries 1, 4, and 10) the reaction of the substrate proceeded rapidly. As a result of the above results, the electron-withdrawing resonance effect by nitrogen in the pyridine of the nitro group of p-nitrobenzaldehyde and 4-pyridine carboxyaldehyde (4-pyridine carboxaldehyde) effect) seems to accelerate the Baylis-Hillman reaction. On the other hand, aromatic aldehydes having aliphatic aldehydes (entry 8) and electron-donating groups (entries 6 and 9) have a relatively slow reaction rate and moderate yields. The reaction proceeded.

또한, 본 발명에서 개발한 트리아졸륨 이온성 액체 [bmTr][PF6](14c)는 기존에 널리 쓰이는 이미다졸륨 이온성 액체 [bmim][PF6]와 구조적으로 유사하지만, C(2)를 N으로 치환함으로써 염기에 안정하고 염기를 사용하는 Baylis-Hillman 반응에서 [bmim][PF6]보다 높은 수득율을 보임을 확인할 수 있었다. In addition, the triazolium ionic liquid [bmTr] [PF 6 ] ( 14c ) developed in the present invention is structurally similar to the imidazolium ionic liquid [bmim] [PF 6 ], which is widely used, but C (2) Substituting for N, it was confirmed that the yield is higher than [bmim] [PF 6 ] in the Baylis-Hillman reaction using the base stable to the base.

메틸methyl 3-(4- 3- (4- 클로로페닐Chlorophenyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로파노에이트Methylenepropanoate (18a)의 합성 Synthesis of 18a

컬럼크로마토그래피(Hexane/EtOAc = 5/1)로 정제하여 원하는 화합물 18a (0.218 g, 96%)를 흰색 고체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 5/1) afforded the desired compound 18a (0.218 g, 96%) as a white solid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.31 (3:1 hexane/EtOAc). mp : 40.7 ℃ (Lit.,: 42 ℃). 1H-NMR (400 MHz, CDCl3) : δ 7.32 (s, 4H), 6.35 (s, 1H), 5.82 (s, 1H), 5.54 (d, 1H, J = 6.0 Hz), 3.74 (s, 3H), 3.03 (d, 1H, J = 6.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ166.8, 141.8, 140.0, 133.8, 128.8, 128.2, 126.6, 72.9, 52.3.TLC: R f 0.31 (3: 1 hexane / EtOAc). mp: 40.7 ° C. (Lit., 42 ° C.). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.32 (s, 4H), 6.35 (s, 1H), 5.82 (s, 1H), 5.54 (d, 1H, J = 6.0 Hz), 3.74 (s, 3H), 3.03 (d, 1H, J = 6.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.8, 141.8, 140.0, 133.8, 128.8, 128.2, 126.6, 72.9, 52.3.

메틸methyl 3- 3- 하이드록시Hydroxy -2-메틸렌-3-(4--2-methylene-3- (4- 피리디닐Pyridinyl )) 프로파노에이트Propanoate (18b)의 합성Synthesis of 18b

컬럼크로마토그래피(Hexane/EtOAc = 1/5)로 정제하여 원하는 화합물 18b (0.181 g, 93%)를 아이보리 결정 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 1/5) afforded the desired compound 18b (0.181 g, 93%) in ivory crystals. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.22 (1:5 = hexane/EtOAc(v/v)). mp : 129.5 ℃ (Lit., : 143-144 ℃ (from EtOH)). 1H-NMR (400 MHz, CDCl3) : δ 8.59 (d, 2H, J = 6.4 Hz), 7.32 (d, 2H, J = 6.4 Hz), 6.39 (s, 1H), 5.85 (s, 1H), 5.51 (d, 1H, J = 6.8 Hz), 3.75 (s, 3H), 3.28 (d, 1H, J = 6.8 Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.6, 150.8, 149.9, 141.1, 127.4, 121.6, 72.4, 52.4. LRMS (FAB) m/z (rel int) : 194 ([M], 35). HRMS m/z calcd for C10H12NO3 194.0817 ; found 194.0813.TLC: R f 0.22 (1: 5 = hexane / EtOAc (v / v)). mp: 129.5 ℃ (Lit., : 143-144 ° C (from EtOH)). 1 H-NMR (400 MHz, CDCl 3 ): δ 8.59 (d, 2H, J = 6.4 Hz), 7.32 (d, 2H, J = 6.4 Hz), 6.39 (s, 1H), 5.85 (s, 1H) , 5.51 (d, 1H, J = 6.8 Hz), 3.75 (s, 3H), 3.28 (d, 1H, J = 6.8 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.6, 150.8, 149.9, 141.1, 127.4, 121.6, 72.4, 52.4. LRMS (FAB) m / z (rel int): 194 ([M], 35). HRMS m / z calcd for C 10 H 12 NO 3 194.0817; found 194.0813.

메틸methyl 3-(2- 3- (2- 퓨릴Furyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로파노에이트(18c)의Of methylene propanoate (18c) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 5/1(v/v))로 정제하여 원하는 화합물 18c(0.156 g, 86%)를 연한 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 5/1 (v / v)) afforded the desired compound 18c (0.156 g, 86%) as a pale yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.46 (2:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.38 (m, 1H), 6.39 (s, 1H), 6.34 (dd, 1H, J = 3.2, 2.0 Hz), 6.27 (d, 1H, J = 3.2 Hz), 5.94 (s, 1H), 5.59 (d, 1H, J = 6.4 Hz), 3.77 (s, 3H), 3.05 (d, 1H, J = 6.4 Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.7, 154.3, 142.6, 139.6, 127.1, 110.6, 107.4, 67.7, 52.3. LRMS (FAB) m/z (rel int) : 165 ([M-OH]+, 100), 182 ([M], 10), 205 ([M+Na]+, 10). HRMS m/z calcd for C9H10O4 182.0579 ; found 182.0574.TLC: R f 0.46 (2: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.38 (m, 1H), 6.39 (s, 1H), 6.34 (dd, 1H, J = 3.2, 2.0 Hz), 6.27 (d, 1H, J = 3.2 Hz), 5.94 (s, 1H), 5.59 (d, 1H, J = 6.4 Hz), 3.77 (s, 3H), 3.05 (d, 1H, J = 6.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.7, 154.3, 142.6, 139.6, 127.1, 110.6, 107.4, 67.7, 52.3. LRMS (FAB) m / z (rel int): 165 ([M-OH] + , 100), 182 ([M], 10), 205 ([M + Na] + , 10). HRMS m / z calcd for C 9 H 10 O 4 182.0579; found 182.0574.

메틸methyl 3-(4- 3- (4- 플로로페닐Florophenyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로파노에이트(18d)의Of methylene propanoate (18d) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 18d (0.171 g, 80%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 18d (0.171 g, 80%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.48 (2:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.35 (dd, 2H, J = 8.8, 6.0 Hz), 7.03 (t, 2H, J = 8.8Hz), 6.34 (s, 1H), 5.82 (s, 1H), 5.55 (d, 1H, J = 5.6 Hz), 3.74 (s, 3H), 2.99 (d, 1H, J = 5.6 Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.9, 162.6 (d, J CF = 244.3 Hz), 142.1, 137.2 (d, J CF = 3.0 Hz), 128.5 (d, J CF = 7.5Hz), 126.3, 115.5 (d, J CF = 21.0 Hz), 72.9, 52.2. LRMS (FAB) m/z (rel int): 193 ([M-OH]+, 91), 233 ([M+Na]+, 14).TLC: R f 0.48 (2: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.35 (dd, 2H, J = 8.8, 6.0 Hz), 7.03 (t, 2H, J = 8.8 Hz), 6.34 (s, 1H), 5.82 (s, 1H), 5.55 (d, 1H, J = 5.6 Hz), 3.74 (s, 3H), 2.99 (d, 1H, J = 5.6 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.9, 162.6 (d, J CF = 244.3 Hz), 142.1, 137.2 (d, J CF = 3.0 Hz), 128.5 (d, J CF = 7.5 Hz), 126.3, 115.5 (d, J CF = 21.0 Hz), 72.9, 52.2. LRMS (FAB) m / z (rel int): 193 ([M-OH] + , 91), 233 ([M + Na] + , 14).

메틸methyl 3- 3- 하이드록시Hydroxy -3-(4--3- (4- 나이트로페닐Nitrophenyl )-2-)-2- 메틸렌프로파노에이트(18e)의Of methylene propanoate (18e) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 18e(0.187 g, 79%)를 노란색의 결정 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 18e (0.187 g, 79%) in yellow crystalline state. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.33 (2:1= hexane/EtOAc(v/v)). mp : 70.2 °C (Lit., : 73-74 °C). 1H-NMR (400 MHz, CDCl3):δ 8.21 (d, 2H, J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 6.40 (s, 1H), 5.87 (s, 1H), 5.63 (d, 1H, J = 6.4 Hz), 3.75 (s, 3H), 3.25 (d, 1H, J = 6.4 Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.6, 148.8, 147.7, 141.2, 127.5, 127.5, 123.9, 73.0, 52.4. LRMS (FAB) m/z (rel int) : 238 ([M+H]+, 5), 260 ([M+Na]+, 5).TLC: R f 0.33 (2: 1 = hexane / EtOAc (v / v)). mp: 70.2 ° C (Lit., : 73-74 ° C). 1 H-NMR (400 MHz, CDCl 3 ): δ 8.21 (d, 2H, J = 8.8 Hz), 7.59 (d, 2H, J = 8.8 Hz), 6.40 (s, 1H), 5.87 (s, 1H) , 5.63 (d, 1H, J = 6.4 Hz), 3.75 (s, 3H), 3.25 (d, 1H, J = 6.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.6, 148.8, 147.7, 141.2, 127.5, 127.5, 123.9, 73.0, 52.4. LRMS (FAB) m / z (rel int): 238 ([M + H] + , 5), 260 ([M + Na] + , 5).

메틸methyl 3- 3- 하이드록시Hydroxy -2-메틸렌-3--2-methylene-3- 페닐프로파노에이트(18f)의Of phenylpropanoate (18f) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 18f (0.149 g, 77%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 18f (0.149 g, 77%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.50 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.40-7.29 (m, 5H), 6.34 (s, 1H), 5.83 (s, 1H), 5.58 (d, 1H, J = 6.0 Hz), 3.73 (s, 3H), 2.98 (d, 1H, J = 6.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.9, 142.2, 141.5, 128.6, 128.0, 126.8, 126.2, 73.3, 52.1. LRMS (FAB) m/z (rel int) : 175 ([M-OH]+, 77), 215 ([M+Na]+, 20).TLC: R f 0.50 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.40-7.29 (m, 5H), 6.34 (s, 1H), 5.83 (s, 1H), 5.58 (d, 1H, J = 6.0 Hz), 3.73 ( s, 3H), 2.98 (d, 1H, J = 6.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.9, 142.2, 141.5, 128.6, 128.0, 126.8, 126.2, 73.3, 52.1. LRMS (FAB) m / z (rel int): 175 ([M-OH] + , 77), 215 ([M + Na] + , 20).

메틸methyl 3- 3- 하이드록시Hydroxy -3-(3,4,5--3- (3,4,5- 트라이메톡시페닐Trimethoxyphenyl )-2-)-2- 메틸렌프로파노에이트(18g)의Of methylene propanoate (18 g) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 2/1(v/v))로 정제하여 원하는 화합물 18g (0.230 g, 81%)를 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 2/1 (v / v)) afforded 18 g (0.230 g, 81%) of the desired compound as a yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.22 (2:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 6.61 (s, 2H), 6.34 (s, 1H), 5.82 (s, 1H), 5.51 (s, 1H), 3.85 (s, 6H), 3.84 (s, 3H), 3.76 (s, 3H), 3.03 (brs, 1H). 13C-NMR (100 MHz, CDCl3) : δ 167.0, 153.4, 142.1, 137.6, 137.1, 126.3, 103.8, 73.3, 60.9, 56.2, 52.2. LRMS (FAB) m/z (rel int) : 265 ([M-OH]+, 84), 282 ([M], 100), 305 ([M+Na]+, 17).TLC: R f 0.22 (2: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 6.61 (s, 2H), 6.34 (s, 1H), 5.82 (s, 1H), 5.51 (s, 1H), 3.85 (s, 6H), 3.84 ( s, 3H), 3.76 (s, 3H), 3.03 (brs, 1H). 13 C-NMR (100 MHz, CDCl 3 ): δ 167.0, 153.4, 142.1, 137.6, 137.1, 126.3, 103.8, 73.3, 60.9, 56.2, 52.2. LRMS (FAB) m / z (rel int): 265 ([M-OH] + , 84), 282 ([M], 100), 305 ([M + Na] + , 17).

메틸methyl 3- 3- 하이드록시Hydroxy -2-메틸렌-5--2-methylene-5- 페닐Phenyl -4--4- 펜티노에이트(18h)의Of pentinoate (18h) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 5/1(v/v))로 정제하여 원하는 화합물 18h (0.147 g, 66%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 5/1 (v / v)) afforded the desired compound 18h (0.147 g, 66%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.30 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.41-7.38 (m, 2H), 7.34-7.30 (m, 2H), 7.25 (m, 1H), 6.68 (d, 1H, J = 12.0 Hz), 6.33-6.28 (m, 2H), 5.92 (s, 1H), 5.13 (t, 1H, J = 6.4 Hz), 3.80 (s, 3H), 2.88 (d, 1H, J = 6.4 Hz). 13C-NMR (100 MHz, CDCl3) : δ 167.1, 153.4, 142.0, 137.7, 137.0, 126.4, 103.8, 73.5, 61.0, 56.3, 52.2. LRMS (FAB) m/z (rel int) : 201 ([M-OH]+, 10), 218 ([M], 4), 241 ([M+Na]+, 4). HRMS m/z calcd for C13H14O3 218.0943 ; found 218.0939.TLC: R f 0.30 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.41-7.38 (m, 2H), 7.34-7.30 (m, 2H), 7.25 (m, 1H), 6.68 (d, 1H, J = 12.0 Hz), 6.33-6.28 (m, 2H), 5.92 (s, 1H), 5.13 (t, 1H, J = 6.4 Hz), 3.80 (s, 3H), 2.88 (d, 1H, J = 6.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 167.1, 153.4, 142.0, 137.7, 137.0, 126.4, 103.8, 73.5, 61.0, 56.3, 52.2. LRMS (FAB) m / z (rel int): 201 ([M-OH] + , 10), 218 ([M], 4), 241 ([M + Na] + , 4). HRMS m / z calcd for C 13 H 14 O 3 218.0943; found 218.0939.

메틸methyl 3- 3- 하이드록시Hydroxy -2--2- 메틸렌펜테이노에이트(18i)의Of methylenepentenoate (18i) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 5/1(v/v))로 정제하여 원하는 화합물 18i (82.1 mg, 47%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 5/1 (v / v)) afforded the desired compound 18i (82.1 mg, 47%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.33 (2:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 6.22 (s, 1H), 5.79 (s, 1H), 4.39 (q, 1H, J = 6.8 Hz), 3.78 (s, 3H), 2.00 (d, 1H, J = 6.8 Hz), 1.68-1.62 (m, 2H), 1.42-1.31 (m, 4H), 0.90 (t, 3H, J = 6.8 Hz). 13C-NMR (100 MHz, CDCl3) : δ 167.2, 142.7, 125.1, 71.9, 52.0, 36.1, 28.2, 22.7, 14.2. LRMS (FAB) m/z (rel int) : 173 ([M+H]+, 51), 195 ([M+Na]+, 6), 367 ([2M+Na]+, 19).TLC: R f 0.33 (2: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 6.22 (s, 1H), 5.79 (s, 1H), 4.39 (q, 1H, J = 6.8 Hz), 3.78 (s, 3H), 2.00 (d, 1H, J = 6.8 Hz), 1.68-1.62 (m, 2H), 1.42-1.31 (m, 4H), 0.90 (t, 3H, J = 6.8 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 167.2, 142.7, 125.1, 71.9, 52.0, 36.1, 28.2, 22.7, 14.2. LRMS (FAB) m / z (rel int): 173 ([M + H] + , 51), 195 ([M + Na] + , 6), 367 ([2M + Na] + , 19).

메틸methyl 3- 3- 하이드록시Hydroxy -3-(4--3- (4- 메톡시페닐Methoxyphenyl )-2-)-2- 메틸렌프로파노에이트(18j)의Of methylene propanoate (18j) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 18j (91.3 mg, 41%)를 흰색의 고체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 18j (91.3 mg, 41%) as a white solid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.36 (2:1=hexane/EtOAc(v/v)). mp : 43.9 ℃ (Lit., : 54-56 ℃). 1H-NMR (400 MHz, CDCl3) : δ 7.30 (d, 2H, J = 8.4 Hz), 6.88 (d, 2H, J = 8.4 Hz), 6.33 (s, 1H), 5.85 (s, 1H), 5.53 (d, 1H, J = 4.8 Hz), 3.80 (s, 3H), 3.72 (s, 3H), 2.84 (d, 1H, J = 4.8 Hz). 13C-NMR (100 MHz, CDCl3) : δ 167.0, 159.5, 142.4, 133.7, 128.1, 125.8, 114.0, 73.0, 55.5, 52.1.TLC: R f 0.36 (2: 1 = hexane / EtOAc (v / v)). mp: 43.9 ° C (Lit., : 54-56 ° C). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.30 (d, 2H, J = 8.4 Hz), 6.88 (d, 2H, J = 8.4 Hz), 6.33 (s, 1H), 5.85 (s, 1H) , 5.53 (d, 1H, J = 4.8 Hz), 3.80 (s, 3H), 3.72 (s, 3H), 2.84 (d, 1H, J = 4.8 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 167.0, 159.5, 142.4, 133.7, 128.1, 125.8, 114.0, 73.0, 55.5, 52.1.

메틸methyl 3- 3- 하이드록시Hydroxy -2-메틸렌-3-(4--2-methylene-3- (4- 트라이플로로메틸페닐Trifluoromethylphenyl )) 프로파노에이트Propanoate (18k)의 합성 Synthesis of 18k

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 18k (0.174 g, 67%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 18k (0.174 g, 67%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.37 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.61 (d, 2H, J = 8.0 Hz), 7.51 (d, 2H, J = 8.0 Hz), 6.38 (s, 1H), 5.84 (s, 1H), 5.61 (d, 1H, J = 6.0 Hz), 3.75 (s, 3H), 3.16 (d, 1H, J = 6.0Hz). 13C-NMR (100 MHz, CDCl3) : δ 166.8, 145.5, 141.6, 130.2 (q, J CF = 32.0 Hz), 127.0, 127.0, 125.6 (q, J CF = 3.8 Hz), 124.3 (q, J CF = 270.2 Hz), 73.0, 52.3.TLC: R f 0.37 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.61 (d, 2H, J = 8.0 Hz), 7.51 (d, 2H, J = 8.0 Hz), 6.38 (s, 1H), 5.84 (s, 1H) , 5.61 (d, 1H, J = 6.0 Hz), 3.75 (s, 3H), 3.16 (d, 1H, J = 6.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 166.8, 145.5, 141.6, 130.2 (q, J CF = 32.0 Hz), 127.0, 127.0, 125.6 (q, J CF = 3.8 Hz), 124.3 (q, J CF = 270.2 Hz), 73.0, 52.3.

<< 실험예Experimental Example 3> 1,3- 3> 1,3- 디알킬Dialkyl -1,2,3--1,2,3- 트리아졸륨Triazium 이온성 액체에서 알데히드와  With aldehydes in ionic liquids 아크Arc 릴로나이트릴의  Lilonitrile BaylisBaylis -- HillmanHillman 반응 실험방법 Reaction Experiment Method

[bmTr][PF6](14c)의 Baylis-Hillman 반응에 대한 적용성을 살펴보기 위해 또 다른 마이클 수용체(Michael acceptor)로서 아크릴로니트릴(acrylonitrile)와 다양한 알데히드를 사용하여 반응성을 확인해 보았다. 즉, 1 mL 용량의 둥근 바닥 플라스크에 알데히드(1.00 mmol)과 DABCO(0.230 g, 2.01 mmol)를 Ar-degassed [bmTr][PF6] 0.1 mL에 녹였다. 아크릴로니트릴 (0.107 g, 2.01 mmol)을 가한 뒤, 상온에서 교반하였다. 반응이 종료된 후, 컬럼크로마토 그래피로 정제하여 원하는 화합물 19a 내지 19j를 얻었다(표 3).In order to examine the applicability of [bmTr] [PF 6 ] ( 14c ) to Baylis-Hillman reaction, acrylonitrile and various aldehydes were confirmed as another Michael acceptor. That is, aldehyde (1.00 mmol) and DABCO (0.230 g, 2.01 mmol) were dissolved in 0.1 mL of Ar-degassed [bmTr] [PF 6 ] in a 1 mL round bottom flask. Acrylonitrile (0.107 g, 2.01 mmol) was added and stirred at room temperature. After the reaction was completed, purification by column chromatography gave the desired compounds 19a to 19j (Table 3).

[표 3] [bmTr][PF6] a 이온성 액체에서 다양한 알데히드와 아크릴로니트릴(acrylonitrile)의 Baylis-Hillman 반응 [Table 3] [bmTr] [PF 6 ] a variety of ionic liquid acrylonitrile and acrylic aldehyde (acrylonitrile) from the Baylis-Hillman reaction

Figure 112009075196023-pat00018
Figure 112009075196023-pat00018

실험예2의 메틸 아크릴레이트의 반응과 비교하여, 모든 반응이 짧은 반응 시간에 걸쳐 높은 수율로 진행되었다. 치환체에 관계없이, 거의 모든 기질이 정량적으로 원하는 Baylis-Hillman 생성물을 얻을 수 있었다. 반면, 퍼퓨랄 (furfural)은 원하는 화합물인 19d가 반응 중에 빠르게 분해하여 중간 정도의 수율로 얻을 수 있었다 (entry 4). 19d는 3급 아민염기 (tertiary amine base)를 사용한 반응 조건에서 불안정한 것으로 보고되어 있다 (V. K. Aggarwal, I. Emme and S. Y. Fulford, J. Org . Chem., 2003, 68, 692.).Compared with the reaction of the methyl acrylate of Experimental Example 2, all the reactions proceeded in high yield over a short reaction time. Regardless of the substituents, almost all substrates were able to quantitatively obtain the desired Baylis-Hillman product. Furfural, on the other hand, could be obtained in medium yield by rapidly decomposing the desired compound 19d during the reaction (entry 4). 19d has been reported to be unstable under reaction conditions with tertiary amine bases (VK Aggarwal, I. Emme and SY Fulford, J. Org . Chem ., 2003, 68 , 692.).

3-(4-3- (4- 클로로페닐Chlorophenyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로페인나이트릴Methylene Propane Nitrile (19a)의 합성 Synthesis of (19a)

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19a (0.196 g, 99%)를 무색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19a (0.196 g, 99%) as a colorless liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.21 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.39 (AB quartet, 2H, J = 8.8 Hz), 7.35 (AB quartet, 2H, J = 8.8 Hz), 6.13 (d, 1H, J = 1.6 Hz), 6.06 (d, 1H, J = 1.6 Hz), 5.32 (m, 1H), 2.30 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 137.8, 135.1, 130.3, 129.3, 128.1, 126.1, 116.9, 73.7.TLC: R f 0.21 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.39 (AB quartet, 2H, J = 8.8 Hz), 7.35 (AB quartet, 2H, J = 8.8 Hz), 6.13 (d, 1H, J = 1.6 Hz) , 6.06 (d, 1H, J = 1.6 Hz), 5.32 (m, 1H), 2.30 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 137.8, 135.1, 130.3, 129.3, 128.1, 126.1, 116.9, 73.7.

3-(4-3- (4- 플로로페닐Florophenyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로페인나이트릴(19b)의Of methylene propanenitrile (19b) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19b (0.177 g, 99%)를 연한 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19b (0.177 g, 99%) as a light yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.20 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.39 (dd, 2H, J = 8.4, 5.2 Hz), 7.10 (t, 2H, J = 8.4 Hz), 6.13 (d, 1H, J = 1.2 Hz), 6.06 (d, 1H, J = 1.2 Hz), 5.32 (d, 1H, J = 4.0 Hz), 2.34 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 163.1 (d, J CF = 246.4 Hz), 135.2 (d, J CF = 2.8 Hz), 130.2, 128.5 (d, J CF = 8.4 Hz), 126.3, 117.0, 116.0 (d, J CF = 21.7 Hz), 73.6.TLC: R f 0.20 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.39 (dd, 2H, J = 8.4, 5.2 Hz), 7.10 (t, 2H, J = 8.4 Hz), 6.13 (d, 1H, J = 1.2 Hz) , 6.06 (d, 1H, J = 1.2 Hz), 5.32 (d, 1H, J = 4.0 Hz), 2.34 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 163.1 (d, J CF = 246.4 Hz), 135.2 (d, J CF = 2.8 Hz), 130.2, 128.5 (d, J CF = 8.4 Hz), 126.3, 117.0, 116.0 (d, J CF = 21.7 Hz), 73.6.

3-3- 하이드록시Hydroxy -2-메틸렌-3-(4--2-methylene-3- (4- 피리디닐Pyridinyl )) 프로페인나이트릴Propane Nitrile (19c)의 합성Synthesis of (19c)

컬럼크로마토그래피(Hexane/EtOAc = 1/5(v/v))로 정제하여 원하는 화합물 19c (0.160 g, 99%)를 주황색의 고체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 1/5 (v / v)) afforded the desired compound 19c (0.160 g, 99%) as an orange solid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.16 (1:5=hexane/EtOAc(v/v)). mp : 102.6 ℃. 1H-NMR (400 MHz, CDCl3) : δ 8.65 (d, 2H, J = 6.0 Hz), 7.36 (d, 2H, J = 6.0 Hz), 6.17 (d, 1H, J = 1.2 Hz), 6.11 (d, 1H, J = 1.2 Hz), 5.35 (s, 1H), 2.73 (s, 1H). 13C-NMR (100 MHz, CDCl3) : δ 149.8, 149.6, 132.1, 125.9, 121.2, 117.0, 71.6.TLC: R f 0.16 (1: 5 = hexane / EtOAc (v / v)). mp: 102.6 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 8.65 (d, 2H, J = 6.0 Hz), 7.36 (d, 2H, J = 6.0 Hz), 6.17 (d, 1H, J = 1.2 Hz), 6.11 (d, 1H, J = 1.2 Hz), 5.35 (s, 1H), 2.73 (s, 1H). 13 C-NMR (100 MHz, CDCl 3 ): δ 149.8, 149.6, 132.1, 125.9, 121.2, 117.0, 71.6.

3-(2-3- (2- 퓨릴Furyl )-3-) -3- 하이드록시Hydroxy -2--2- 메틸렌프로파인나이트릴Methylenepropinenitrile (19d)의 합성 Synthesis of 19d

컬럼크로마토그래피 (Hexane/EtOAc = 4/1(v/v))로 정제하여 원하는 화합물 19d (76.4 mg, 51%)를 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 4/1 (v / v)) afforded the desired compound 19d (76.4 mg, 51%) as a yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.50 (1:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.44 (m, 1H), 6.44 (m, 1H), 6.40 (dd, 1H, J = 3.2, 1.6 Hz), 6.20 (d, 1H, J = 1.6 Hz), 6.15 (d, 1H, J = 1.6 Hz), 5.37 (d, 1H, J = 5.6 Hz), 2.38 (d, 1H, J = 5.6 Hz). 13C-NMR (100 MHz, CDCl3) : δ 151.6, 143.6, 131.4, 123.6, 116.8, 111.0, 109.0, 68.0.TLC: R f 0.50 (1: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.44 (m, 1H), 6.44 (m, 1H), 6.40 (dd, 1H, J = 3.2, 1.6 Hz), 6.20 (d, 1H, J = 1.6 Hz), 6.15 (d, 1H, J = 1.6 Hz), 5.37 (d, 1H, J = 5.6 Hz), 2.38 (d, 1H, J = 5.6 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 151.6, 143.6, 131.4, 123.6, 116.8, 111.0, 109.0, 68.0.

3-3- 하이드록시Hydroxy -2-메틸렌-3-(4--2-methylene-3- (4- 나이트로페닐Nitrophenyl )) 프로페인나이트릴Propane Nitrile (19e)의 합성Synthesis of 19e

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19e (0.198 g, 97%)를 연한 노란색의 결정 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19e (0.198 g, 97%) in light yellow crystals. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.38 (1:1=hexane/EtOAc(v/v)). mp : 72.1 ℃ (Lit.,24 : 72-75 ℃). 1H-NMR (400 MHz, CDCl3) : δ 8.28 (d, 2H, J = 8.8 Hz), 7.62 (d, 2H, J = 8.8 Hz), 6.20 (d, 1H, J = 1.6 Hz), 6.12 (d, 1H, J = 1.6 Hz), 5.46 (d, 1H, J = 4.0 Hz), 2.52 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 148.4, 146.0, 131.1, 127.6, 125.6, 124.3, 116.4, 73.6.TLC: R f 0.38 (1: 1 = hexane / EtOAc (v / v)). mp: 72.1 ° C. (Lit., 24 : 72-75 ° C.). 1 H-NMR (400 MHz, CDCl 3 ): δ 8.28 (d, 2H, J = 8.8 Hz), 7.62 (d, 2H, J = 8.8 Hz), 6.20 (d, 1H, J = 1.6 Hz), 6.12 (d, 1H, J = 1.6 Hz), 5.46 (d, 1H, J = 4.0 Hz), 2.52 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 148.4, 146.0, 131.1, 127.6, 125.6, 124.3, 116.4, 73.6.

3-3- 하이드록시Hydroxy -2-메틸렌-3--2-methylene-3- 페닐프로페인나이트릴(19f)의Of phenylpropanenitrile (19f) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19f (0.158 g, 99%)를 탁한 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19f (0.158 g, 99%) in a turbid liquid state. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.22 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.42-7.37 (m, 5H), 6.13 (d, 1H, J = 1.6 Hz), 6.06 (d, 1H, J = 1.6 Hz), 5.33 (m, 1H), 2.26 (d, 1H, J = 4.0 Hz). 13C-NMR (100MHz, CDCl3) : δ 139.3, 130.1, 129.1, 126.7, 126.3, 117.1, 74.2.TLC: R f 0.22 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.42-7.37 (m, 5H), 6.13 (d, 1H, J = 1.6 Hz), 6.06 (d, 1H, J = 1.6 Hz), 5.33 (m, 1H), 2.26 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 139.3, 130.1, 129.1, 126.7, 126.3, 117.1, 74.2.

3-3- 하이드록시Hydroxy -3-(3,4,5--3- (3,4,5- 트라이메톡시페닐Trimethoxyphenyl )-2-)-2- 메틸렌프로페인나이트릴(19g)의Of methylene propane nitrile (19 g) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 2/1(v/v))로 정제하여 원하는 화합물 19g (0.294 g, 99%)를 흰색 결정 상태로 얻었다. Purification by column chromatography (Hexane / EtOAc = 2/1 (v / v)) afforded 19 g (0.294 g, 99%) of the desired compound as white crystals.

TLC : R f 0.19 (1:1=hexane/EtOAc(v/v)). mp : 78.5 ℃. 1H-NMR (400 MHz, CDCl3) : δ 6.61 (s, 2H), 6.13 (d, 1H, J = 1.6 Hz), 6.06 (d, 1H, J = 1.6 Hz), 5.25 (m, 1H), 3.87 (s, 6H), 3.85 (s, 3H), 2.35 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 153.7, 138.4, 135.1, 129.9, 126.3, 117.2, 103.7, 74.5, 61.1, 56.4.TLC: R f 0.19 (1: 1 = hexane / EtOAc (v / v)). mp: 78.5 ° C. 1 H-NMR (400 MHz, CDCl 3 ): δ 6.61 (s, 2H), 6.13 (d, 1H, J = 1.6 Hz), 6.06 (d, 1H, J = 1.6 Hz), 5.25 (m, 1H) , 3.87 (s, 6H), 3.85 (s, 3H), 2.35 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 153.7, 138.4, 135.1, 129.9, 126.3, 117.2, 103.7, 74.5, 61.1, 56.4.

3-3- 하이드록시Hydroxy -2-메틸렌-5--2-methylene-5- 페닐Phenyl -4--4- 펜틴나이트릴(19h)의Of pentine nitrile (19h) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19h (0.162 g, 87%)를 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19h (0.162 g, 87%) as a yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.18 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.43-7.29 (m, 5H), 6.76 (d, 1H, J = 12.0 Hz), 6.22 (dd, 1H, J = 12.0, 6.8 Hz), 6.12 (d, 1H, J = 1.6 Hz), 6.05 (d, 1H, J = 1.6 Hz), 4.94 (m, 1H), 2.07 (d, 1H, J = 4.4 Hz). 13C-NMR (100 MHz, CDCl3) : δ 135.8, 133.9, 130.3, 128.9, 128.6, 127.0, 126.8, 125.6, 117.2, 73.0.TLC: R f 0.18 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.43-7.29 (m, 5H), 6.76 (d, 1H, J = 12.0 Hz), 6.22 (dd, 1H, J = 12.0, 6.8 Hz), 6.12 ( d, 1H, J = 1.6 Hz), 6.05 (d, 1H, J = 1.6 Hz), 4.94 (m, 1H), 2.07 (d, 1H, J = 4.4 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 135.8, 133.9, 130.3, 128.9, 128.6, 127.0, 126.8, 125.6, 117.2, 73.0.

3-3- 하이드록시Hydroxy -3-(4--3- (4- 메톡시페닐Methoxyphenyl )-2-)-2- 메틸렌프로페인나이트릴(19i)의Of methylene propanenitrile (19i) 합성 synthesis

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19i (0.187 g, 98%)를 노란색의 액체 상태로 얻었다. Spectral data를 참고문헌과 비교하여 확인하였다.Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19i (0.187 g, 98%) as a yellow liquid. Spectral data was confirmed by comparison with the reference.

TLC : R f 0.17 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.31 (d, 2H, J = 8.8 Hz), 6.92 (d, 2H, J = 8.8 Hz), 6.12 (d, 1H, J = 1.6 Hz), 6.03 (d, 1H, J = 1.6 Hz), 5.27 (m, 1H), 3.82 (s, 3H), 2.26 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 160.3, 131.6, 129.6, 128.2, 126.6, 117.2, 114.6, 74.0, 55.5.TLC: R f 0.17 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.31 (d, 2H, J = 8.8 Hz), 6.92 (d, 2H, J = 8.8 Hz), 6.12 (d, 1H, J = 1.6 Hz), 6.03 (d, 1H, J = 1.6 Hz), 5.27 (m, 1H), 3.82 (s, 3H), 2.26 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 160.3, 131.6, 129.6, 128.2, 126.6, 117.2, 114.6, 74.0, 55.5.

3-3- 하이드록시Hydroxy -2-메틸렌-3-(4--2-methylene-3- (4- 트라이플로로메틸페닐Trifluoromethylphenyl )) 프로페인나이트릴Propane Nitrile (19j)의 합성Synthesis of (19j)

컬럼크로마토그래피(Hexane/EtOAc = 3/1(v/v))로 정제하여 원하는 화합물 19j (0.212 g, 93%)를 연한 노란색의 액체 상태로 얻었다. Purification by column chromatography (Hexane / EtOAc = 3/1 (v / v)) afforded the desired compound 19j (0.212 g, 93%) as a light yellow liquid.

TLC : R f 0.24 (3:1=hexane/EtOAc(v/v)). 1H-NMR (400 MHz, CDCl3) : δ 7.68 (d, 2H, J = 8.4 Hz), 7.55 (d, 2H, J = 8.4 Hz), 6.16 (d, 1H, J = 1.6 Hz), 6.09 (d, 1H, J = 1.6 Hz), 5.41 (m, 1H), 2.44 (d, 1H, J = 4.0 Hz). 13C-NMR (100 MHz, CDCl3) : δ 143.1, 131.2 (q, J CF = 32.4 Hz), 130.8, 127.0, 126.1 (q, J CF = 3.8 Hz), 125.9, 124.1 (q, J CF = 270.5 Hz), 116.7, 73.7.TLC: R f 0.24 (3: 1 = hexane / EtOAc (v / v)). 1 H-NMR (400 MHz, CDCl 3 ): δ 7.68 (d, 2H, J = 8.4 Hz), 7.55 (d, 2H, J = 8.4 Hz), 6.16 (d, 1H, J = 1.6 Hz), 6.09 (d, 1H, J = 1.6 Hz), 5.41 (m, 1H), 2.44 (d, 1H, J = 4.0 Hz). 13 C-NMR (100 MHz, CDCl 3 ): δ 143.1, 131.2 (q, J CF = 32.4 Hz), 130.8, 127.0, 126.1 (q, J CF = 3.8 Hz), 125.9, 124.1 (q, J CF = 270.5 Hz), 116.7, 73.7.

<< 실험예Experimental Example 4> 본 발명의 이온성 액체의 다양한 용매와의  4> with the various solvents of the ionic liquid of the present invention 섞임성Mixing 확인  Confirm

일반적으로 생성물과 부산물은 유기 용매나 물을 이용하여 단순 추출을 통해 이온성 액체층에서 분리할 수 있고, 생성물과 부산물의 분리 후, 이온성 액체는 재사용할 수 있다. 그러므로, 다양한 용매에 대한 이온성 액체의 용해도는 재사용시 중요 요인으로 작용한다. 따라서, 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체의 재활용 가능성을 확인하기 위해 여러 용매에 대한 용해도를 확인해 보았다(표4).In general, products and by-products can be separated from the ionic liquid layer by simple extraction using organic solvents or water, and after separation of the products and by-products, the ionic liquid can be reused. Therefore, the solubility of ionic liquids in various solvents is an important factor in reuse. Therefore, solubility in various solvents was checked to confirm the recyclability of the 1,3-dialkyl-1,2,3-triazolium ionic liquid (Table 4).

[표 4] 다양한 1,3-디알킬-1,2,3-트리아졸륨 이온성 액체와 다양한 유전상수 (dielectric constant b )의 용매와의 섞임성 (Miscibility a ) [Table 4] Blending of the various 1,3-dialkyl-1,2,3-triazolium ionic liquid and a solvent different dielectric constants (dielectric constant b) sex (Miscibility a)

Figure 112009075196023-pat00019
Figure 112009075196023-pat00019

용해도는 용매의 유전 상수 (dielectric constant)와 상관 관계가 있다. 1,3- 디알킬-1,2,3-트리아졸륨 이온성 액체는 헥산(hexane)과 에테르(Et2O)에 녹지 않지만 디클로로메탄(CH2Cl2)이나 아세트산 에틸(ethylacetate)에는 녹았다. 물에 대한 용해도는 이온성 액체의 음이온에 의해 결정되었다. NTf2 염과 PF6 염은 물에 녹지 않았으나, BF4 염은 녹았다. 1-부틸-3-메틸-1,2,3-트리아졸륨 이온성 액체 [bmTr][PF6]의 용해도는 도.1 에서 확인된다(도. 1은 일반 용매와 [bmTr][PF6]의 섞임성을 나타내며, 구체적으로, A : Hexane (상층) 및 [bmTr][PF6] (하층), B: Et2O (상층) 및 [bmTr][PF6] (하층), C : EtOAc 및 [bmTr][PF6] (섞임), D: CH2Cl2 및 [bmTr][PF6] (섞임), E: H2O (상층) 및 [bmTr][PF6] (하층)을 나타낸다).Solubility correlates with the dielectric constant of the solvent. 1,3-dialkyl-1,2,3-triazolium ionic liquid is insoluble in hexane and ether (Et 2 O) but in dichloromethane (CH 2 Cl 2 ) or ethyl acetate (ethylacetate) . Solubility in water was determined by the anion of the ionic liquid. NTf 2 and PF 6 salts were not dissolved in water, but BF 4 salts were dissolved. 1-butyl-3-methyl-1,2,3-triazolium ionic liquid [bmTr] The solubility of [PF 6] is identified in Fig. 1 (Fig. 1 is a general solvent and [bmTr] [PF 6] In particular, A: Hexane (upper layer) and [bmTr] [PF 6 ] (lower layer), B: Et 2 O (upper layer) and [bmTr] [PF 6 ] (lower layer), C: EtOAc And [bmTr] [PF 6 ] (mixed), D: CH 2 Cl 2 And [bmTr] [PF 6 ] (mixed), E: H 2 O (upper layer) and [bmTr] [PF 6 ] (lower layer)).

<< 실험예Experimental Example 5> 본 발명의 이온성 액체의 반복 사용 효과 확인  5> Confirm the effect of repeated use of the ionic liquid of the present invention

화학적 안정성과 비휘발성으로 인해 이온성 액체는 여러 번의 회수-재사용이 가능하며, 환경을 해치는 폐기물의 생성과 반응 과정에서 생기는 폐기물 처리 비용을 줄여 "친환경 용매"의 기준을 만족한다. 따라서 p-클로로벤즈알데히드와 아크릴로니트릴의 반응에서 본 발명에서 개발한 [bmTr][PF6](14c)의 회수-재사용이 가능한지 여부를 하기와 같은 방법으로 확인 하였으며, 그 결과는 [표 5]와 같다.Due to their chemical stability and non-volatility, ionic liquids can be recovered and reused many times, meeting the criteria of "green solvents" by reducing the waste disposal costs associated with the generation of hazardous wastes and reactions. Therefore, whether or not recovery and reuse of the [bmTr] [PF 6 ] ( 14c ) developed in the present invention in the reaction of p-chlorobenzaldehyde and acrylonitrile was confirmed by the following method. Same as

실험 방법: [Experiment method: [ bmTrbmTr ][] [ PFPF 66 ] 이온성 액체의 재사용Reuse of Ionic Liquids

1 mL 용량의 둥근 바닥 플라스크에 4-클로로벤즈알데하이드 (0.431 g, 3.01 mmol), 아크릴로니트릴 (0.321 g, 6.02 mmol), 그리고 DABCO (0.69 g, 6.03 mmol)를 [bmTr][PF6] (0.409 g, 0.3 mL)에 녹였다. 상온에서 교반하면서 반응상태를 TLC로 확인했다.In a 1 mL round bottom flask, 4-chlorobenzaldehyde (0.431 g, 3.01 mmol), acrylonitrile (0.321 g, 6.02 mmol), and DABCO (0.69 g, 6.03 mmol) were added to [bmTr] [PF 6 ] ( 0.409 g, 0.3 mL). The reaction was confirmed by TLC while stirring at room temperature.

방법 A : 반응이 종료된 후, 에테르 (5X5 mL)를 이용하여 생성물을 [bmTr][PF6]에서 추출하였다. 에테르 층을 감압 농축한 후, 컬럼크로마토그래피 (hexane/EtOAc = 3/1(ㅍ/v))로 정제하여 원하는 화합물 19a (0.553 g, 95%)를 얻었다. 회수한 이온성 액체 (0.414 g)는 감압하여 다음 반응에 재사용 하였다. Method A : After the reaction was completed, the product was extracted in [bmTr] [PF 6 ] using ether (5X5 mL). The ether layer was concentrated under reduced pressure, and then purified by column chromatography (hexane / EtOAc = 3/1 (p / v)) to obtain the desired compound 19a (0.553 g, 95%). The recovered ionic liquid (0.414 g) was decompressed and reused in the next reaction.

방법 B : 반응이 종료된 후, 컬럼크로마토그래피 (hexane/EtOAc = 3/1(v/v) → MeOH)로 정제하여 원하는 화합물 19a (0.577 g, 99%)와 이온성 액체 (0.563 g)를 얻었다. 회수한 이온성 액체는 감압하여 다음 반응에 재사용하였다. Method B : After the reaction was completed, purification by column chromatography (hexane / EtOAc = 3/1 (v / v)-MeOH) gave the desired compound 19a (0.577 g, 99%) and the ionic liquid (0.563 g). Got it. The recovered ionic liquid was decompressed and reused in the next reaction.

[표 5] 이온성 액체 [bmTr][PF6] a 의 회수-재사용 Table 5 Ionic Liquid [bmTr] [PF 6 ] a Recovery-reuse

Figure 112009075196023-pat00020
Figure 112009075196023-pat00020

상기 [표 5]에서 살펴본 바와 같이, 방법 B는 방법 A와 달리 별도의 추출과 정 없이 컬럼크로마토 그래피를 이용하여 [bmTr][PF6](14c)를 회수한 결과이다. 그 결과, 두 방법 모두 4차례의 [bmTr][PF6](14c) 회수-재사용 시도에서 수율의 큰 변화 없이 생성물을 얻을 수 있었다(표 5).As shown in Table 5, Method B, unlike Method A, is a result of recovering [bmTr] [PF 6 ] ( 14c ) using column chromatography without separate extraction process. As a result, both methods yielded the product without significant change in yield in four [bmTr] [PF 6 ] ( 14c) recovery-reuse attempts (Table 5).

도 1은 일반 용매와 [bmTr][PF6]의 섞임성을 나타내는 사진이다. 1 is a photograph showing the mixing property of a general solvent and [bmTr] [PF 6 ].

Claims (17)

염기성 조건 반응의 반응용매로서의 하기 화학식 1의 이온성 액체:An ionic liquid of formula 1 as a reaction solvent for a basic conditional reaction: [화학식 1][Formula 1]
Figure 112011080511292-pat00021
Figure 112011080511292-pat00021
 상기 식에서, R1 은 n-부틸이며, R2는 각각 C1-4의 알킬기이고, X는 NTf2(bis((trifluoromethyl)sulfonyl)amide), PF6(hexafluorophosphate) 또는 BF4(tetrafluoroborate)이다.Wherein R 1 is n-butyl, R 2 is each an alkyl group of C 1-4, and X is NTf 2 (bis ((trifluoromethyl) sulfonyl) amide), PF 6 (hexafluorophosphate) or BF 4 (tetrafluoroborate). 제1항에 있어서, R2는 메틸기 또는 n-부틸기인 이온성 액체.The ionic liquid of claim 1, wherein R 2 is a methyl group or n-butyl group. 제2항에 있어서, R2는 n-부틸기인 이온성 액체. The ionic liquid of claim 2, wherein R 2 is an n-butyl group. 삭제delete 삭제delete 제1항에 있어서, R2는 메틸기인 이온성 액체.The ionic liquid of claim 1, wherein R 2 is a methyl group. 삭제delete 제1항에 있어서, 염기성 조건 반응이 Baylis-Hillman 반응인 이온성 액체.The ionic liquid of claim 1, wherein the basic conditional reaction is a Baylis-Hillman reaction. 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete 삭제delete
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Journal of Material Chemistry, 13, 2003, pp.2451-2456*
Organic Letters, 6(23), 2004, pp.4223-4225*

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