CN101372479B - Compound containing 2- bromovinyl-1,2,3-triazole and one-pot preparation thereof - Google Patents
Compound containing 2- bromovinyl-1,2,3-triazole and one-pot preparation thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of drug intermediate synthesis, and more particularly relates to a compound containing 2-ethylene bromide-1, 2, 3-triazole and a one-pot preparation method thereof. The compound takes 4-azido-cinnamylate and alkyne as materials, and multiple triazole compounds can be conveniently synthesized under the catalysis of copper by adopting the 'one-pot method'. The structure of the triazole compounds which are synthesized by the invention contains alkene bromine and nitrogen heterocycle, and is an important drug synthesis intermediate, and has very important application prospect in the fields of biomedicine and medicament; the triazole compounds is widely applied clinically. The method adopts the 'one-pot method', has simple operation method, mild reaction conditions, low cost and better application prospect, and is easy for commercial process.
Description
Technical field
The invention belongs to the pharmaceutical intermediate synthesis technical field, relate to a kind of 2-of containing bromo vinyl-1,2,3-3-triazole compounds and one-pot preparation thereof thereof.
Background technology
1,2, the 3-3-triazole compounds is one type of very important compound, and the five-membered ring in the triazole class compounds has lower toxicity as pharmacophoric group than imidazoles
[1]On agricultural, be widely used as Insecticides (tech) & Herbicides (tech), plant-growth regulator etc., in industry, often be applied to brightening agent, anticolodal of pigment etc.Pharmaceutically using the most extensively, this compounds does not exist at occurring in nature, all is the method preparation by chemosynthesis.Triazole ring demonstrates multiple biological activity as pharmacophoric group, and existing numerous triazole derivative is widely used in clinical as medicine such as antimycotic, antiviral, antitumor, anticonvulsion.Triazole class compounds has become drug research and one of hot of research and development and major fields in recent years, has shown broad development potentiality
[2]The synthetic alkene of highly-solid selectively is one of most important focus of organic synthesis always, in synthetic natural product with physiologically active and medicine, has very important significance, and the bromo alkene with suitable or anti-configuration is very important pharmaceutical intermediate fragment
[3]Use preparation 1,2 always, the method for 3-3-triazole compounds is to realize through organic nitrine and alkynes cycloaddition reaction, but the reaction back often generates two kinds of isomer, and stereoselectivity is relatively poor, and the separation of compound is purified makes troubles, and has also wasted raw material simultaneously, has increased the three wastes
[4]Sharpless etc. use click-reaction under copper catalysis, utilize organic nitrine and alkyne reaction successfully to synthesize 1,2 of highly-solid selectively, the 3-3-triazole compounds
[5,6]The present invention utilizes 4-azido-styracin and alkyne reaction " one kettle way " to realize this dick's reaction of the Chinese and click-reaction simultaneously on this basis, successfully synthesizes a kind of 2-of containing bromo vinyl-1,2, the 3-3-triazole compounds.
Reference:
[1]Pauw，D.D.E.Int.J.Antimicrob.Agents.2000，16，147.
[2] white snow, Zhou Chenghe, Mi Jiali. chemical research and application .2007,17,721.
[3]Duncton，M.A.J.；Pattenden，G.J.Chem.Soc.，Perkin?Trans.11999，1235.
[4]Huisgen，R.Angew.Chem.1963，75，604.
[5]Rostovtsev，V.V.；Green，L.G.；Fokin，V.V.；Sharpless，K.B.Angew.Chem.，Int.Ed.2002，41，2596.
[6]Chan，T.R.；Robert，H.；Sharpless，K.B.；Fokin，V.V.Org.Lett.2004，6，2853.
Summary of the invention
The object of the invention is to provide a kind of 2-of containing bromo vinyl-1,2,3-3-triazole compounds and one-pot preparation thereof thereof.
The present invention proposes contains 2-bromo vinyl-1,2, the 3-3-triazole compounds, and its general structure is following:
Wherein, R be in aryl, substituted aryl, fatty group, sulphonamide phenyl or the ester group any.
The 2-bromo vinyl-1,2 that contains provided by the invention, the 3-3-triazole compounds, its compound is specific as follows:
In any.
The present invention proposes contains 2-bromo thiazolinyl-1,2, the preparation method of 3-3-triazole compounds; With Lithium Acetate, sodium ascorbate as additive; The nitrogen bromo-succinimide obtains trans-4-azido-beta-bromstyrol as brominated reagent, under cuprous iodide or cupric sulfate pentahydrate effect, realizes 1 of alkynes and triazo-compound again; The 3-cycloaddition reaction, its synthetic route is following:
Concrete steps are following:
1) preparation of trans-4-azido-beta-bromstyrol
In round-bottomed flask, add 4-azido-styracin, Lithium Acetate, as solvent, be stirred to solution and clarify with acetonitrile and water; Add the nitrogen bromo-succinimide, TLC adds water, ethyl acetate extraction after showing that reaction is accomplished in reaction system; The organic phase washing, anhydrous sodium sulfate drying filters; Rotary evaporation in vacuo is removed ETHYLE ACETATE, the red-brown oily liquids trans-4-azido-beta-bromstyrol.Wherein, the mol ratio of 4-azido-styracin and Lithium Acetate is 1:0.2-1:0.4, and the mol ratio of 4-azido-styracin and nitrogen bromo-succinimide is 1:1.0-1:1.1, and the mol ratio of 4-azido-styracin and acetonitrile is 1:70-1:100.
2) 2-bromo vinyl-1,2, the preparation of 3-3-triazole compounds
1.1 the mol ratio of 4-azido-styracin and acetonitrile is 1:70-1:100.
Among the present invention, said alkynes be in phenylacetylene, 4-bromobenzene acetylene, 4-nitrobenzene acetylene, 4-sulfonanilide base phenylacetylene, N-methyl-4-sulfonanilide base phenylacetylene or the ethyl propiolate any.
Among the present invention, the volume ratio of said acetonitrile and water is 5:1-9:1.
The present invention is a raw material with 4-azido-styracin cheap and easy to get, carries out cycloaddition reaction with alkynes " one kettle way " under the effect of nitrogen bromo-succinimide, Lithium Acetate, sodium ascorbate, cuprous iodide etc. and obtains multiple triazole class compounds.This synthetic route employing " one kettle way ", raw material are easy to get, easy and simple to handle, advantages such as reaction conditions is gentle, the reaction times is short, saving solvent, minimizing pollution, are convenient to suitability for industrialized production.
Embodiment
Followingly further specify the present invention, but can not limit content of the present invention through embodiment.
Embodiment 1:
1) preparation compound I
The synthetic route of compound I such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), phenylacetylene 102mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 2.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 296mg, yield 91%.
Characterization data is following:
1HNMR(500MHz，CDCl
3)：δ6.90(1H，d，J＝14.00Hz)，7.16(1H，d，J＝14.00Hz)，7.37-7.49(5H，m)，7.78(2H，d，J＝8.50Hz)，7.91(2H，d，J＝8.50Hz)，8.19(1H，s).
2) preparation compound I I
The synthetic route of compound I I such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), 4-bromobenzene acetylene 180mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 2.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 364mg, yield 90%.
Characterization data is following:
1HNMR(300MHz，DMSO-d
6)：δ7.32(1H，d，J＝14.00Hz)，7.46(1H，d，J＝14.00Hz)，7.72(2H，d，J＝8.10Hz)，7.75(2H，d，J＝8.10Hz)，7.90(2H，d，J＝8.50Hz)，7.94(2H，d，J＝8.50Hz)，9.38(1H，s).
3) preparation compound III
The synthetic route of compound III such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), 4-nitrobenzene acetylene 147mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 2.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 307mg, yield 83%.
Characterization data is following:
1HNMR(300MHz，DMSO-d
6)：δ7.32(1H，d，J＝14.00Hz)，7.47(1H，d，J＝14.00Hz)，7.76(2H，d，J＝8.70Hz)，7.96(2H，d，J＝8.70Hz)，8.21(2H，d，J＝8.70Hz)，8.39(2H，d，J＝8.70Hz)，9.59(1H，s).
4) preparation compound IV
The synthetic route of compound IV such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), 4-sulfonanilide base phenylacetylene 257mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 2.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate pale yellow powder 409mg, yield 85%.
Characterization data is following:
1HNMR(300MHz，DMSO-d
6)：δ7.03-7.24(5H，m)，7.32(1H，d，J＝14.00Hz)，7.45(1H，d，J＝14.00Hz)，7.75((2H，d，J＝8.70Hz)，7.87(2H，d，J＝8.70Hz)，7.93(2H，d，J＝8.40Hz)，8.08(2H，d，J＝8.40Hz)，9.43(1H，s)
.5) preparation compound V
The synthetic route of compound V such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), N-methyl-4-sulfonanilide base phenylacetylene 271mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 3.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, and anhydrous sodium sulfate drying is used in organic phase washing 3 times.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate light brown powder 401mg, yield 81%.Characterization data is following:
1HNMR(500MHz，CDCl
3：DMSO-d
6)：δ3.25(3H，s)，6.95(1H，d，J＝14.00Hz)，7.11-7.12(2H，m)，7.18(1H，d，J＝14.00Hz)，7.29-7.34(3H，m)，7.52(2H，d，J＝8.50Hz)，7.62(2H，d，J＝8.50Hz)，7.83(2H，d，J＝8.50Hz)，8.04(2H，d，J＝8.50Hz)，8.61(1H，s).
6) preparation compound VI
The synthetic route of compound VI such as following formula; In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 5:1) make solvent; Add nitrogen bromo-succinimide 178mg (1mmol), ethyl propiolate 98mg (1mmol), sodium ascorbate 20mg (0.1mmol), cuprous iodide 19mg (0.1mmol) successively, nitrogen protection, room temperature reaction 2.5 hours after being stirred to the solution clarification.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, and anhydrous sodium sulfate drying is used in organic phase washing 3 times.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate white powder 303mg, yield 94%.
Characterization data is following:
1HNMR(500MHz，CDCl
3)：δ1.37(3H，t，J＝7.00Hz)，4.40(2H，q，J＝7.00Hz)，6.84(1H，d，J＝14.00Hz)，7.09(1H，d，J＝14.00Hz)，7.42(2H，d，J＝8.50Hz)，7.67(2H，d，J＝8.50Hz)，8.44(1H，s).
Embodiment 2:
1) preparation compound I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), phenylacetylene 112mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 300mg, yield 92%.
2) preparation compound I I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-bromobenzene acetylene 198mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 368mg, yield 91%.
3) preparation compound III
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-nitrobenzene acetylene 161mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 4 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 310mg, 84%.
4) preparation compound IV
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-sulfonanilide base phenylacetylene 282mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, and anhydrous sodium sulfate drying is used in organic phase washing 3 times.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate pale yellow powder 413mg, yield 86%.
5) preparation compound V
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), N-methyl-4-sulfonanilide base phenylacetylene 298mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate light brown powder 406mg, yield 82%.
6) preparation compound VI
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 20mg (0.2mmol); Acetonitrile and water 5mL (volume ratio 6:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), ethyl propiolate 108mg (1.1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate white powder 306mg, yield 95%.
Embodiment 3:
1) preparation compound I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), phenylacetylene 102mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 293mg, yield 90%.
2) preparation compound I I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-bromobenzene acetylene 180mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 364mg, yield 90%.
3) preparation compound III
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-nitrobenzene acetylene 147mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 4 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 303mg, yield 82%.
4) preparation compound IV
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), 4-sulfonanilide base phenylacetylene 257mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate pale yellow powder 404mg, yield 84%.
5) preparation compound V
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), N-methyl-4-sulfonanilide base phenylacetylene 271mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate light brown powder 400mg, yield 81%.
6) preparation compound VI
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 31mg (0.3mmol); Acetonitrile and water 5mL (volume ratio 7:1) make solvent; Add nitrogen bromo-succinimide 187mg (1.05mmol), ethyl propiolate 98mg (1mmol), sodium ascorbate 30mg (0.15mmol), cuprous iodide 29mg (0.15mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate white powder 305mg, yield 95%.
Embodiment 4:
1) preparation compound I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), phenylacetylene 112mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 299mg, yield 92%.
2) preparation compound I I
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), 4-bromobenzene acetylene 198mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 367mg, yield 91%.
3) preparation compound III
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), 4-nitrobenzene acetylene 161mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 4 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate yellow powder 301mg, yield 84%.
4) preparation compound IV
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), 4-sulfonanilide base phenylacetylene 282mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, organic phase washing 3 times, anhydrous sodium sulfate drying.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate pale yellow powder 410mg, yield 85%.
5) preparation compound V
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), N-methyl-4-sulfonanilide base phenylacetylene 298mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 3.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, and anhydrous sodium sulfate drying is used in organic phase washing 3 times.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate light brown powder 405mg, yield 82%.
6) preparation compound VI
In round-bottomed flask, add 4-azido-styracin 189mg (1mmol), Lithium Acetate 40mg (0.4mmol); Acetonitrile and water 5mL (volume ratio 9:1) make solvent; Add nitrogen bromo-succinimide 196mg (1.1mmol), ethyl propiolate 108mg (1.1mmol), sodium ascorbate 40mg (0.2mmol), cuprous iodide 38mg (0.2mmol) successively after being stirred to the solution clarification; Nitrogen protection, room temperature reaction 2.5 hours.TLC adds entry after showing that reaction is accomplished in reaction system, use ethyl acetate extraction, tells organic phase, and anhydrous sodium sulfate drying is used in organic phase washing 3 times.Rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate white powder 304mg, yield 94%.
Claims (4)
1. one kind contains 2-bromo vinyl-1,2, and the 3-3-triazole compounds is characterized in that the structural formula of this compound does
In any.
2. 2-bromo vinyl-1,2 that contains as claimed in claim 1, the one-pot preparation thereof of 3-3-triazole compounds is characterized in that concrete steps are following:
In round-bottomed flask, add 4-azido-styracin, Lithium Acetate, as solvent, after being stirred to solution and clarifying, add nitrogen bromo-succinimide, alkynes, sodium ascorbate and cuprous iodide successively with acetonitrile and water; Under nitrogen atmosphere, room temperature reaction 2.5-4 hour, after TLC shows that reaction is accomplished; In reaction system, add entry and ethyl acetate extraction, tell organic phase, the organic phase washing; Anhydrous sodium sulfate drying, rotary evaporation in vacuo is removed ETHYLE ACETATE, silicagel column separate required product; Wherein, The mol ratio of 4-azido-styracin and alkynes is 1: 1-1: 1.1; The mol ratio of 4-azido-styracin and cuprous iodide is 1: 0.1-1: 0.2, and the mol ratio of 4-azido-styracin and sodium ascorbate is 1: 0.1-1: 0.2, the mol ratio of 4-azido-styracin and Lithium Acetate is 1: 0.2-1: 0.4; The mol ratio of 4-azido-styracin and nitrogen bromo-succinimide is 1: 1.0-1: 1.1, and the mol ratio of 4-azido-styracin and acetonitrile is 1: 70-1: 100.
3. preparation method according to claim 2, it is characterized in that said alkynes be in phenylacetylene, 4-bromobenzene acetylene, 4-nitrobenzene acetylene, 4-sulfonanilide base phenylacetylene, N-methyl-4-sulfonanilide base phenylacetylene or the ethyl propiolate any.
4. preparation method according to claim 2, the volume ratio that it is characterized in that acetonitrile and water is 5: 1-9: 1.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4689334A (en) * | 1983-03-18 | 1987-08-25 | The University Of Kentucky Research Foundation | Triazoline anticonvulsant compounds and compositions |
| CN1039345A (en) * | 1988-07-08 | 1990-02-07 | 先灵农业化学品公司 | Triazole insecticides |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4689334A (en) * | 1983-03-18 | 1987-08-25 | The University Of Kentucky Research Foundation | Triazoline anticonvulsant compounds and compositions |
| CN1039345A (en) * | 1988-07-08 | 1990-02-07 | 先灵农业化学品公司 | Triazole insecticides |
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