CN101205207B - Method for synthesizing [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate - Google Patents
Method for synthesizing [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate Download PDFInfo
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- CN101205207B CN101205207B CN2006101653161A CN200610165316A CN101205207B CN 101205207 B CN101205207 B CN 101205207B CN 2006101653161 A CN2006101653161 A CN 2006101653161A CN 200610165316 A CN200610165316 A CN 200610165316A CN 101205207 B CN101205207 B CN 101205207B
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Abstract
The invention relates to a synthesis method for [6-(2-ethylsuleenyl propyl)-2, 4-dioxo-3-propionyl] hydroxycyclohexane carboxylate. The diethyly malonate or dimethyl malonate and the 6-ethylthio-3-hepten-2-ketone sodium ethoxide or sodium methoxide solution are mixed together in a molar ratio of 1:1:1 so as to carry out a reaction; the propionyl is added in the solution drop by drop at a temperature ranging from 0 DEG C to 10 DEG C, the mixtures are washed using the water and extracted using the dichloromethane, and then the obtained compounds are dissolved in the xylene by 20 times; the temperature of the solution is raised to 138 DEG C before the 4-N, N-P dimethylamino pyridine is added in the solution; the obtained solution is refluxed for 3 hours and the organic phase is washed using 10ml of 10 per cent hydrochloride, and the xylene is removed through the distillation. Under the circumstance that the acidification step is omitted and the acid binding agents are omitted, the invention obtains the intermediate, [6-(2-ethylsuleenyl propyl)-2, 4-dioxo-3-propionyl] hydroxycyclohexane carboxylate, and the yield reaches up to 60.8 per cent to 75 per cent.
Description
Technical field:
The present invention relates to the synthetic method of a kind of [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate, its target compound can be used for the synthetic of weeding active compound.
Background technology:
[6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate is the important intermediate of synthetic herbicide, existing synthetic route mainly is that 6-ethylmercapto group-3-hepten-2-one and diethyl malonate carry out cycloaddition and obtain compd A under strong alkali catalyst (as sodium ethylate) catalysis; Use acid (example hydrochloric acid) acidifying compd A then; obtain [6-(2-ethylsuleenyl propyl)-2; the 4-dioxo] the cyclohexyl acetic acid ethyl ester; then at acid binding agent (as triethylamine; salt of wormwood etc.) exist down and esterifying reagents such as propionyl chloride or propionic anhydride react compd B; again with it at 4-N, reset under N dimethylamine yl pyridines (DMAP) catalysis intermediate [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate.This method is used in the acid and is adopted after the compd A again and carry out esterification under the acid binding agent condition, consumes equimolar acid and equimolar acid binding agent, and the salts solution of acid binding agent and acid solution discharging simultaneously also can exert an influence to environment.
Summary of the invention:
The object of the invention is to study a kind of its salt that directly utilizes and replaces acid binding agent; do not use the acid treatment compd A; have reducing cost, reduce pollution, simplify the remarkable advantage of synthesis step; be useful for the synthetic method of industrial [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate.
The synthetic method of the present invention discloses a kind of [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate.
Technological line of the present invention is as follows:
The present invention at first carries out cycloaddition with 6-ethylmercapto group-3-hepten-2-one and cycloaddition reagent under sodium alkoxide catalysis; synthetic compound A; then compd A directly and propionyl chloride carry out esterification; synthetic compound B; compd B under DMAP catalysis, reset intermediate [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate.
Concrete technology comprises:
Cycloaddition reagent and 6-ethylmercapto group-3-hepten-2-one are added in the alkaline alcoholic solution successively, alkali and determining alcohol are 2.2mol/L, in molar ratio, and highly basic: cycloaddition reagent: 6-ethylmercapto group-3-hepten-2-one=1: 1: 1, stirred 4 hours down at 76 ℃, get the alcoholic solution of compd A; Temperature is at 0 ℃～10 ℃, and the best is under 2 ℃ of conditions, in the alcoholic solution of above-mentioned compd A, slowly drip propionyl reagent, propionyl reagent is 1～2 times of 6-ethylmercapto group-3-hepten-2-one by weight, and the best is 1.2 times, keeps temperature not to be higher than 5 ℃, dropwised in 30 minutes, thin-layer chromatography detection reaction terminal point, through water washing, dichloromethane extraction 20ml, obtain the compd B crude product, productive rate 95%; The gained compd B is dissolved in the dimethylbenzene; the dimethylbenzene quality is 20 times of compd B quality; be warming up to 138 ℃, add DMAP, refluxed 3 hours; salt acid elution organic phase with 10ml 10%; underpressure distillation removes removal xylene, gets [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate; productive rate 75%, overall yield are 71%.
Described highly basic is sodium ethylate or sodium methylate;
Described cycloaddition reagent is diethyl malonate or dimethyl malonate, and is corresponding with above-mentioned alkali;
Described propionyl reagent is propionyl chloride or propionic anhydride;
Positively effect of the present invention is: reducing the acidifying step, saving under the situation of acid binding agent and obtained intermediate [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate, and obtained good productive rate.
Concrete embodiment:
Embodiment 1:
Synthesizing of compd A:
Get sodium 0.25g (10.9mmol), add the 10ml dehydrated alcohol, the speed that adds sodium is advisable to keep little boiling.Sodium ethylate is cooled to 20 ℃, stirs and drip 1.75g diethyl malonate (10.9mmol) and 6-ethylmercapto group-3-hepten-2-one 1.87g (10.9mmol), reflux 4 hours down.The TLC detection reaction is finished, and gets the ethanolic soln of compd A.
Synthesizing of compd B:
Get (10.9mmol) of the ethanolic soln of compd A, place thermometer is housed, in the three-necked flask of the 100ml of constant pressure funnel and reflux condensing tube, temperature was at 2 ℃ in ice-water bath made.Slowly splash into 1.25mL new system propionyl chloride (12.7mmol), yellow insolubles occurs, keep temperature not to be higher than 5 ℃.Dropwised in 30 minutes.TLC detects, and raw material disappears.In three-necked flask, add 15ml water, close with 3 * 7ml dichloromethane extraction, and organic phase, anhydrous sodium sulfate drying spends the night.The elimination siccative removes solvent under reduced pressure, compd B 3.56g (theoretical yield: 3.71g), productive rate 96%.
Synthesizing of [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate:
Compd B is dissolved in the dimethylbenzene (the dimethylbenzene quality is 20 times of quality product), is warming up to 138 ℃, add DMAP (0.18g), refluxed 3 hours.Hydrochloric acid with 10% (10ml) washing organic phase, aqueous phase discarded, organic phase pressure reducing and steaming dimethylbenzene gets [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate 2.67g (theoretical yield 3.56g), productive rate 75%.
Embodiment 2
Sodium methylate (6.5g, 25% methanol solution, 30mmol) be added drop-wise to 6-ethylmercapto group-3-hepten-2-one (4.3g, 25mmol) in, add then dimethyl malonate (3.3g, 25mmol).Cooling was kept room temperature 15 minutes, stirred under the room temperature and spent the night.TLC (thin-layer chromatography) proved response is complete.In mixture, add 50ml dimethylbenzene, remove ethanol under reduced pressure, treat that ethanol is thoroughly steamed and remove in system, to add propionic anhydride (3.25g, 25mmol) and DMAP (0.31g, 2.5mmol).Be heated to 130 ℃, and keep this temperature to stir 5 hours. finish with TLC (thin-layer chromatography) proved response, collect product.Get product 5.20g, productive rate is 60.8%.
Embodiment 3:
Synthesizing of [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate:
Get sodium 1.0g (43.5mmol), add the 40ml dehydrated alcohol, the speed that adds sodium is advisable to keep little boiling.Sodium ethylate is cooled to 20 ℃, stirs and in 1 hour, drip 7.0g diethyl malonate (43.5mmol) and 6-ethylmercapto group-3-hepten-2-one 7.5g (43.5mmol) down, reflux 4 hours, TLC detects no raw material residue.Get the ethanolic soln 47ml of compd A.Get the ethanolic soln of compd A, place thermometer is housed, in the three-necked flask of the 100ml of constant pressure funnel and reflux condensing tube, temperature was at 2 ℃ in ice-water bath made.Slowly splash into 5.0mL new system propionyl chloride (50.8mmol), yellow insolubles occurs, keep temperature not to be higher than 5 ℃, be added dropwise to complete in 30 minutes.TLC detects, and raw material disappears.Add 30ml water in three-necked flask, merge organic phase with 3 * 15ml dichloromethane extraction, anhydrous sodium sulfate drying spends the night.The elimination siccative is spin-dried for solvent, gets compd B 14.24g.The gained compd B is dissolved in the dimethylbenzene (the dimethylbenzene quality is 20 times of quality product), is warming up to the dimethylbenzene boiling, add DMAP (0.72g) and refluxed 3 hours.Hydrochloric acid with 10% (15ml) washing organic phase, aqueous phase discarded, organic phase pressure reducing and steaming dimethylbenzene, the thick product 10.70g (theoretical yield 14.84g) of [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate.Overall yield 72%.
Claims (1)
1. one kind [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] synthetic method of cyclohexyl ethyl formate, it is characterized in that: cycloaddition reagent and 6-ethylmercapto group-3-hepten-2-one are added in the alkaline alcoholic solution successively, highly basic and alcohol are 2.2mol/L, in molar ratio, highly basic: cycloaddition reagent: 6-ethylmercapto group-3-hepten-2-one=1: 1: 1, stirred 4 hours down at 76 ℃, get the alcoholic solution of compd A; Temperature is under 0 ℃～10 ℃ conditions, in the alcoholic solution of above-mentioned compd A, slowly drip propionyl reagent, propionyl reagent is 1～2 times of 6-ethylmercapto group-3-hepten-2-one by weight, keeps temperature＜5 ℃, dropwises in 30 minutes, thin-layer chromatography detection reaction terminal point, through water washing, the 20ml dichloromethane extraction obtains the compd B crude product; The gained compd B is dissolved in the dimethylbenzene, the dimethylbenzene quality is 20 times of compd B quality, be warming up to 138 ℃, add 4-N, the N dimethylamine yl pyridines refluxed 3 hours, salt acid elution organic phase with 10ml 10%, distillation removes removal xylene, gets [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate;
Described highly basic is sodium ethylate or sodium methylate;
Described cycloaddition reagent is diethyl malonate or dimethyl malonate, and is corresponding with above-mentioned alkali;
The solvent of described reaction is ethanol or methyl alcohol;
Described propionyl reagent is propionyl chloride or propionic anhydride.
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| CN2006101653161A CN101205207B (en) | 2006-12-18 | 2006-12-18 | Method for synthesizing [6-(2-ethylsuleenyl propyl)-2,4-dioxo-3-propionyl] cyclohexyl ethyl formate |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5118856A (en) * | 1983-04-23 | 1992-06-02 | Basf Aktiengesellschaft | Preparation of cyclohexane-dione derivatives |
| US6300281B1 (en) * | 2000-07-03 | 2001-10-09 | Valent U.S.A. Corporation | Optically pure(−) clethodim, compositions and methods for controlling plant growth comprising the same |
| JP2001288161A (en) * | 2000-04-10 | 2001-10-16 | Nippon Soda Co Ltd | Method for producing substituted alicyclic-1,3-dione |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5118856A (en) * | 1983-04-23 | 1992-06-02 | Basf Aktiengesellschaft | Preparation of cyclohexane-dione derivatives |
| JP2001288161A (en) * | 2000-04-10 | 2001-10-16 | Nippon Soda Co Ltd | Method for producing substituted alicyclic-1,3-dione |
| US6300281B1 (en) * | 2000-07-03 | 2001-10-09 | Valent U.S.A. Corporation | Optically pure(−) clethodim, compositions and methods for controlling plant growth comprising the same |
Non-Patent Citations (2)
| Title |
|---|
| 杨博友.环己烯酮类除草剂.农药30 1.1991,30(1),48-50. |
| 杨博友.环己烯酮类除草剂.农药30 1.1991,30(1),48-50. * |
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