CN1271021C - Process for synthesizing sex pheromone of pine caterpillar - Google Patents
Process for synthesizing sex pheromone of pine caterpillar Download PDFInfo
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- CN1271021C CN1271021C CN 200410021734 CN200410021734A CN1271021C CN 1271021 C CN1271021 C CN 1271021C CN 200410021734 CN200410021734 CN 200410021734 CN 200410021734 A CN200410021734 A CN 200410021734A CN 1271021 C CN1271021 C CN 1271021C
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Abstract
The present invention relates to a preparation method of pine caterpillar sex pheromones, which belongs to the technical field of the preparation of insect pheromones. Acetylene and acrolein are used as initial raw materials, key intermediates (4Z, 6E)-4, 6-undecadienal are obtained by rections in four steps, and the pine caterpillar sex pheromones (5Z, 7E)-5, 7-dodecadienal-1-alcohol, acetate ((5Z, 7E)-5, 7-dodecadienal ester and propionate (5Z, 7E)-5, 7-dodecadienal ester. The present invention has the characteristics of short synthesizing route, easily obtained raw materials, ideal yield, low cost, etc. and is suitable for industrialized production.
Description
Technical field: the present invention relates to a kind of synthetic and preparation method of pine moth pheromone, belong to field of insect pheromone preparing technology.
Background technology: pine moth pheromone is the secretory product of the female moth of pine moth, and it is to male rising property of moth attracting action, by compound (5Z; 7E)-5; 7-12 carbon diene-1-alcohol, acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z; 7E)-5; 7-12 carbon diene esters are formed (its structural formula is shown in accompanying drawing one) by a certain percentage, can be used for detecting and reporting pest information and pest control, and it is strong that pest control has specificity; nuisanceless, advantages such as protection natural enemy.This compound since separated identifying in 1971, existing so far multiple synthetic method.As Institute of Zoology, Academia Sinica from acetylene hydrocarbon compound through Wittig prepared in reaction compd A [referring to document: Science Bulletin, 25,1004,1979].The TetsuAndo of Japan etc. are that raw material has synthesized compd A C referring to document: Agric.Boil.Chem, 49 (1), 141,1985 through the Wittig reaction with the omega-diol].Tetsu Ando etc. also reported with E type haloalkene and Terminal Acetylenes coupling again the selective reduction acetylene bond be the method [referring to document Agric.Biol.Chem., 46 (3), 717,1982] of Z type ethylene linkage stereospecificity synthetic compound A.Renzo Rossi etc. has also reported another kind of synthetic method similarly [referring to document Tetrahedron, 39 (3), 287,1983].Preceding two kinds of methods have the condition harshness and are difficult for shortcomings such as industrialization, stereoselectivity difference owing to use the Wittig reaction, and reactions steps is also more in addition.The two kinds of method stereoselectivity height in back high academic value is arranged, but reactions steps are more, condition harshness, and raw material costliness, and suitability for industrialized production is worth little.
Summary of the invention: for overcoming above-mentioned the deficiencies in the prior art, it is short to the invention provides a kind of synthetic route, and raw material is easy to get, and total recovery is more satisfactory and be convenient to the method for synthetic this compound of suitability for industrialized production.
To achieve these goals, the invention provides following technical scheme: 1. starting raw material acetylene and propenal prepare Compound C under Pd catalysis, and Compound C does not need purifying promptly to can be used for next step reaction; 2. Compound C obtains Compound D through the ethylene glycol protection under acidic conditions; 3. Compound D obtains compd E with the organometallic compound coupling under Pd catalysis, and used catalyzer can be Pd (PPh
3)
4, PdCl
2---PPh
3, Pd (PP
3)
2Cl
2:, used organometallic compound can be butyl Grignard reagent or butyllithium, and solvent can be benzene or tetrahydrofuran (THF).Its optimum reaction condition is Pd (PPh
3)
4, monobutyl Grignard reagent one benzene, temperature of reaction is a room temperature; 4. reaction was 2 hours under compd E was preferably in 65 ℃ in 80%HOAc, obtained key intermediate B; Compd B in anhydrous diethyl ether with CH
3OCH
2The Wittig reagent react of Cl obtains compound F 17-hydroxy-corticosterone; 6. compound F 17-hydroxy-corticosterone hydrolysis under acidic conditions obtains compound G, and used reaction conditions is an acetate: tetrahydrofuran (THF): water=3: 1: 1, the best 40-80 of temperature of reaction ℃; 7. compound G NaBH
4, reduction obtains target product A1, and A2, A3 are made through esterification by Al.
The detailed technology scheme of the synthetic method of pine moth pheromone is that employing acetylene and propenal are starting raw material, preparation compound 7-bromo under the catalysis of palladium salt-(4Z, 6E)-4, the 6-heptadienal, promptly according to the method for the scorching ZL96116429.8 patent record of Lu Xi, with Pd (OAc)
2Or PdCl
2, propenal, LiBr or Li
2CO
3Be dissolved in HOAc and H
2O is cooled to and feeds the acetylene stirring reaction after the room temperature, and an amount of distilled water of impouring use dichloromethane extraction, and drying is concentrated, the residuum underpressure distillation promptly obtain compound 7-bromo-(4Z, 6E)-4, the 6-heptadienal; Obtain compound 7-bromo-(4Z; 6E)-4; behind the 6-heptadienal; again to its carry out ethylene glycol protection obtain compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal; under Pd catalysis, obtain compound (4Z then with the coupling of organometallic compound reagent; 6E)-4,6-11 carbon diene Glycol Acetal, used catalyzer is Pd (PPh
3)
4Or PdCl
2-PPh
3, Pd (PPh
3)
2Cl
2In any, used organometallic compound is butyl Grignard reagent or butyllithium, solvent be in benzene or tetrahydrofuran (THF), the ether any, its reaction conditions is Pd (PPh
3)
4Or PdCl
2-PPh
3, Pd (PPh
3)
2Cl
2-butyl Grignard reagent or butyllithium-benzene or tetrahydrofuran (THF), ether, temperature of reaction are 10～40 ℃; Preferred reaction conditions is Pd (PPh
3)
4, the butyl Grignard reagent, benzene, temperature of reaction is 10～40 ℃; With (4Z, 6E)-4,6-11 carbon diene Glycol Acetal hydrolysis under acidic conditions obtain key intermediate (4Z, 6E)-4, the 6-undecadienal, used reaction conditions is: so that any makes solvent and exchanger in acetone or butanone, ether, the tetrahydrofuran (THF), carry out catalyzed reaction, backflow 20-40 minute with sulfuric acid or hydrochloric acid, acetic acid; Or make solvent with tetrahydrofuran (THF), and 5～10% hydrochloric acid catalysis reaction, reaction is 8-50 hour under the room temperature; Or in 50-80%HOAc, react 2～4 hours (available hydrochloric acid or acetic acid are made catalyzer) down at 10～80 ℃; (4Z, 6E)-4, the 6-undecadienal through Wittig reaction obtain compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins, preparation CH
3OCH
2The Wittig reagent place of Cl is t-BuOK, NaOEt with alkali, and reaction medium is anhydrous diethyl ether or tetrahydrofuran (THF), and temperature of reaction is 10～80 ℃; Temperature of reaction is preferably 10～50 ℃, again with (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, the hydrolysis under acidic conditions of 7-12 carbon triolefins obtain compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs, reaction conditions is: acetate-tetrahydrofuran (THF)-water or perchloric acid-ether-water, temperature of reaction are 10～80 ℃; Use NaBH at last
4Or KBH
4With compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs reduction (solvent can be methyl alcohol or ethanol) obtain target product (5Z, 7E)-5,7-12 carbon diene-1-alcohol.Compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol through esterification can make acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5,7-12 carbon diene esters.
It is starting raw material that the present invention adopts acetylene and propenal, through four-step reaction obtain key intermediate (4Z, 6E)-4, the 6-undecadienal, again through three-step reaction obtain target product (5Z, 7E)-5,7-12 carbon diene-1-alcohol.Compared with prior art has following advantage: 1. synthetic route novelty, reactions steps is less. and the general thought of prior art all is to manage to introduce another pair key again after forming two keys, step is various, and the present invention is based on after the conjugated double bond that forms two particular configuration, introduce the thinking of other groups again, thereby step is less, and stereoselectivity is good.
2. raw material is easy to get, and is with low cost.Each step desired raw material of the present invention and various chemical reagent are chemical commonly used, low price, thereby with low cost.
3. yield is more satisfactory, and is easy and simple to handle.Each goes on foot reaction yield all more than 70%, and mild condition, is convenient to suitability for industrialized production, and each goes on foot product only need carry out fractionation by distillation, has simplified operations such as separation and purification greatly.
The present invention only needs the reaction of seven steps can prepare target product from simple raw material acetylene and propenal, has higher suitability for industrialized production and is worth.
Description of drawings: the invention will be further described below in conjunction with embodiment
Fig. 1 be pine moth pheromone of the present invention (5Z, 7E)-5,7-12 carbon diene-1-alcohol (I), acetate (5Z, 7E)-5,7-12 carbon diene esters (II, propionic acid (5Z, 7E)-5, the structure iron (III) of 7-12 carbon diene esters;
Fig. 2 is pine moth pheromone synthetic line figure of the present invention.Wherein C be the 7-bromo-(4Z, 6E)-4,6-heptadienal structure iron, D are 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal structure iron, E be (4Z, 6E)-4,6-11 carbon diene Glycol Acetal structure iron, B are (4Z, 6E)-4,6-undecadienal structure iron, F be (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefin structure iron, G be (5Z, 7E)-5,7-12 carbon diene aldehyde structure figure.
Embodiment: embodiment 1: adopting acetylene and propenal is starting raw material, through four-step reaction obtain key intermediate (4Z, 6E)-4, the 6-undecadienal, obtain pine moth pheromone (5Z through three-step reaction again, 7E)-5, and 7-12 carbon diene-1-alcohol, acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5,7-12 carbon diene esters.Concrete steps and method are:
Preparation 7-bromo-(4Z, 6E)-4, the 6-heptadienal
With 107mgPd (OAc)
2(0.5mmol), 12.6g propenal (225mmol), 26gLiBr (300mmol) is dissolved in 20ml HOAc and 4ml H
2O is cooled to room temperature, feeds acetylene, stirring reaction 12h, impouring 20ml distilled water use dichloromethane extraction, and is dry concentrated, the residuum underpressure distillation obtain compound 7-bromo-(4Z, 6E)-4,6-heptadienal (9.7g), productive rate (based on Pd): 10300%.
Preparation 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal
With 9.4g compound 7-bromo-(4Z, 6E)-4,6-heptadienal (0.05mol), 3.7g ethylene glycol (0.06mol), 3 85% phosphoric acid and 30ml methylene dichloride reflux (installation water trap) azeotropic dehydration after the cooling, are used NaHCO till do not have reaction water to tell
3Solution and water washing, dry concentrating, the residuum underpressure distillation, obtain compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (10.7g), productive rate: 92.0%.
3. preparation (4Z, 6E)-4,6-11 carbon diene Glycol Acetal
With 9.4g compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (40mmol) is dissolved in 400ml benzene, adds 1.4gPd (PPh
3)
4(1.16mmol), behind 20 ℃ of stirring 30min, slowly add the 200ml benzole soln of 60mmol normal-butyl Grignard reagent under the argon shield; mixing solutions stirs fully reaction; reaction mixture boils off most of benzene, adds 80ml water, uses extracted with diethyl ether; dry concentrating; the residuum underpressure distillation, obtain compound (4Z, 6E)-4; 6-11 carbon diene Glycol Acetal (6.0g), productive rate: 71.0%.
4. preparation (4Z, 6E)-4, the 6-undecadienal
(4Z, 6E)-4,6-11 carbon diene Glycol Acetal (20mmol) are dissolved in 80ml 80%HOAc and 20ml H with the 4.2g compound
2In the mixed solvent of O, 60 ℃ are stirred 2h down, with the saturated Na of reaction mixture impouring 300ml
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (4Z, 6E)-4,6-undecadienal (3.12g), productive rate: 94.0%.
Preparation (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins
Ph3P with 14.2g
+CH
2OCH
3Cl
-Mixing obtains soup compound with the 300ml anhydrous diethyl ether, stirs this soup compound under argon shield, slowly adds 4.7gt-BuOK, obtains red solution, restir 3.5h; Then with the 3g compound (4Z, 6E)-4,6-undecadienal (18mmol) is diluted in the 130ml anhydrous diethyl ether, slowly is added drop-wise in this red solution reaction mixture, spends the night at 10 ℃ of following stirring reactions; Add 60ml water again, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (2.85g), productive rate: 80.0%.
6. preparation (5Z, 7E)-5,7-12 carbon two olefine aldehydrs
With 1.9g compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (5mmol) are dissolved in 24mlHOAc, 8mlTHF and 8mlH
2In the mixed solvent of O, 40 ℃ of following stirrings are spent the night, with the saturated Na of reaction mixture impouring 90ml
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (1.64g), productive rate: 91.0%.
7. preparation (5Z, 7E)-5,7-12 carbon diene-1-alcohol
With the 1.35g compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (7.5mmol) and 0.15g sodium borohydride are dissolved in the 40ml methyl alcohol, and add a 6mol/LNaOH aqueous solution, stirred 4 hours down at 0 ℃, boil off methyl alcohol, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (0.96g), productive rate: 71.0%.
MS(m/z)：182(M
+)，164，139，136，135，125，121，111，107，97，93，79，67
1HNMR(CDCl
3，δ，ppm)：6.30(ddd，1H)，5.98(ddd，1H)，5.68(dt，1H)，5.31(dt，1H)，3.65(m，2H)，2.20(m，2H)，2.10(m，2H)，1.61(m，2H)，1.48(m，2H)，1.35(m，4H)，0.90(t，3H)
13CNMR(CDCl
3，δ，ppm)：135.4，12.98，129.4，125.9，62.9，33.0，32.6，31.9，27.8，26.3，22.7，14.3
IR (cm
-1, liquid film): 330 (wide), 3030,2940,2870,1458,1433,1379,1056,981,948
The preparation acetate (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g diacetyl oxide (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 3h is in the impouring frozen water, remove all pyridines with 10% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound acetate (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 72.0%.
The preparation propionic acid (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g propionic anhydride (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 4h is in the impouring frozen water, remove all pyridines with 9% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound propionic acid (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 68.0%.
Embodiment 2: pine moth pheromone (5Z, 7E)-5,7-12 carbon diene-1-alcohol, acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5, the synthesis step and the method for 7-12 carbon diene esters are:
Preparation 7-bromo-(4Z, 6E)-4, the 6-heptadienal
With 107mg PdCl
2(0.5mmol), 12.6g propenal (225mmol), 26g Li
2CO
3(300mmol) be dissolved in 20ml HOAc and 4ml H
2O is cooled to room temperature, feeds acetylene, stirring reaction 12h, impouring 20ml distilled water use dichloromethane extraction, and is dry concentrated, the residuum underpressure distillation obtain compound 7-bromo-(4Z, 6E)-4,6-heptadienal (9.7g), productive rate (based on Pd): 10300%.
Preparation 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal
With 9.4g compound 7-bromo-(4Z, 6E)-4,6-heptadienal (0.05mol), 3.7g ethylene glycol (0.06mol), 3 85% phosphoric acid and 30ml methylene dichloride reflux (installation water trap) azeotropic dehydration after the cooling, are used NaHCO till do not have reaction water to tell
3Solution and water washing, dry concentrating, the residuum underpressure distillation, obtain compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (10.7g), productive rate: 92.0%.
3. preparation (4Z, 6E)-4,6-11 carbon diene Glycol Acetal
With 9.4g compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (40mmol) is dissolved in 400ml benzene, adds 1.4g PdCl
2-PPh
3(1.16mmol), behind stirring at room 30min, the 200ml tetrahydrochysene furan that slowly adds the 60mmol butyllithium is fed reagent solution under the argon shield; mixing solutions stirs and spends the night; reaction mixture boils off most of tetrahydrofuran (THF), adds 80ml water, uses extracted with diethyl ether; dry concentrating; the residuum underpressure distillation, obtain compound (4Z, 6E)-4; 6-11 carbon diene Glycol Acetal (6.0g), productive rate: 71.0%.
4. preparation (4Z, 6E)-4, the 6-undecadienal
With the 4.2g compound (4Z, 6E)-4,6-11 carbon diene Glycol Acetal (20mmol) are dissolved in 80ml and make solvent with tetrahydrofuran (THF), the hydrochloric acid with 5% comes catalyzed reaction, under the room temperature reaction 20 hours, with the saturated Na of reaction mixture impouring 300ml
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (4Z, 6E)-4,6-undecadienal (3.12g), productive rate: 94.0%.
Preparation (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins
Ph with 14.2g
3P
+CH
2OCH
3Cl
-Mixing obtains soup compound with the 300ml anhydrous diethyl ether, stirs this soup compound under argon shield, and divides adding 4.7gNaOH four times, obtains red solution, restir 1.5h; Then with the 3g compound (4Z, 6E)-4,6-undecadienal (18mmol) is diluted in the 130ml anhydrous diethyl ether, and slowly is added drop-wise in this red solution reaction mixture with the 3h time, at 50 ℃ of following stirring reaction 24h; Add 60ml water again, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (2.85g), productive rate: 80.0%.
6. preparation (5Z, 7E)-5,7-12 carbon two olefine aldehydrs
With 1.9g compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (5mmol) are dissolved in 24ml perchloric acid, the 4ml ether mixed solvent, 80 ℃ are stirred down 15h, with the saturated Na of reaction mixture impouring 90ml
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (1.64g), productive rate: 91.0%.
7. preparation (5Z, 7E)-5,7-12 carbon diene-1-alcohol
With the 1.35g compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (7.5mmol) and 0.15g POTASSIUM BOROHYDRIDE are dissolved in the 40ml methyl alcohol, and add a 6mol/LNaOH aqueous solution, stir 4h down at 0 ℃, boil off methyl alcohol, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (0.96g), productive rate: 71.0%.
The preparation acetate (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g diacetyl oxide (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 3h is in the impouring frozen water, remove all pyridines with 10% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound acetate (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 72.0%.
The preparation propionic acid (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g propionic anhydride (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 3h is in the impouring frozen water, remove all pyridines with 10% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound acetate (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 68.0%.
Embodiment 3: pine moth pheromone (5Z, 7E)-5,7-12 carbon diene-1-alcohol, acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5, the synthesis step and the method for 7-12 carbon diene esters are:
Preparation 7-bromo-(4Z, 6E)-4, the 6-heptadienal
With 107mgPd (OAc)
2(0.5mmol), 12.6g propenal (225mmol), 26g Li
2CO
3(300mmol) be dissolved in 20mlHOAc and 4ml H
2O is cooled to room temperature, feeds acetylene stirring reaction 10h, and impouring 20ml distilled water use dichloromethane extraction, and is dry concentrated, the residuum underpressure distillation obtain compound 7-bromo-(4Z, 6E)-4,6-heptadienal (9.7g), productive rate (based on Pd): 10300%.
Preparation 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal
With 9.4g compound compound 7-bromo-(4Z, 6E)-4,6-heptadienal (0.05mol), 3.7g ethylene glycol (0.06mol), 3 85% phosphoric acid and 30ml methylene dichloride reflux (installation water trap) azeotropic dehydration after the cooling, are used NaHCO till do not have reaction water to tell
3Solution and water washing, dry concentrating, the residuum underpressure distillation, obtain compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (10.7g), productive rate: 92.0%.
3. preparation (4Z, 6E)-4,6-11 carbon diene Glycol Acetal
With 9.4g compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal (40mmol) is dissolved in 400ml benzene, adds 1.4g Pd (PPh
3) 2Cl
2(1.16mmol), behind stirring at room 30min, slowly add the 200ml benzole soln of 60mmol normal-butyl Grignard reagent under the argon shield; mixing solutions stirs and spends the night; reaction mixture boils off most of benzene, adds 80ml water, uses extracted with diethyl ether; dry concentrating; the residuum underpressure distillation, obtain compound (4Z, 6E)-4; 6-11 carbon diene Glycol Acetal (6.0g), productive rate: 71.0%.
4. preparation (4Z, 6E)-4, the 6-undecadienal
(4Z, 6E)-4,6-11 carbon diene Glycol Acetal (20mmol) are dissolved among the 80ml80%HOAc, react 4 hours down at 60 ℃, with the saturated Na of reaction mixture impouring 300ml with the 4.2g compound
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (4Z, 6E)-4,6-undecadienal (3.12g), productive rate: 94.0%.
Preparation (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins
Ph3P with 14.2g
+CH
2OCH
3Cl
-Mixing obtains soup compound with the 300ml anhydrous diethyl ether, stirs this soup compound under argon shield, and divides adding 4.7gNaOH three times, obtains red solution, restir 1.5h; Then with the 3g compound (4Z, 6E)-4,6-undecadienal (18mmol) is diluted in the 130ml anhydrous diethyl ether, and slowly is added drop-wise in this red solution reaction mixture with the 3h time, at 30 ℃ of following stirring reaction 24h; Add 60ml water again, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (2.85g), productive rate: 80.0%.
6. preparation (5Z, 7E)-5,7-12 carbon two olefine aldehydrs
With 1.9g compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins (5mmol) are dissolved in 24mlHOAc, 8mlTHF and 8mlH
2In the mixed solvent of O, 60 ℃ are stirred 17h down, with the saturated Na of reaction mixture impouring 90ml
2CO
3In the solution, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (1.64g), productive rate: 91.0%.
7. preparation (5Z, 7E)-5,7-12 carbon diene-1-alcohol
With the 1.35g compound (5Z, 7E)-5,7-12 carbon, two olefine aldehydrs (7.5mmol) and 0.15g sodium borohydride are dissolved in the 40ml methyl alcohol, and add a 6mol/LNaOH aqueous solution, stir 4h down at 0 ℃, boil off methyl alcohol, use extracted with diethyl ether, dry concentrating, the residuum underpressure distillation, obtain compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (0.96g), productive rate: 71.0%.
The preparation acetate (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g diacetyl oxide (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 3h is in the impouring frozen water, remove all pyridines with 10% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound acetate (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 65.0%.
The preparation propionic acid (5Z, 7E)-5,7-12 carbon diene esters
With the 0.37g compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol (2mmol), 0.25g propionic anhydride (2.5mmol) and 0.22g pyridine (2.8mmol) mix, reflux 3h is in the impouring frozen water, remove all pyridines with 10% hcl acidifying, use extracted with diethyl ether, dry concentrated, the residuum underpressure distillation, obtain compound acetate (5Z, 7E)-5,7-12 carbon diene esters (0.31g), productive rate: 72.0%.
Embodiment 4～9: pine moth pheromone (5Z, 7E)-5,7-12 carbon diene-1-alcohol, acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5, the synthesis step and the method for 7-12 carbon diene esters are:
1,2 step preparation 7-bromos-(4Z, 6E)-4,6-heptadienal and 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal is with the 1st, 2 steps of embodiment 1;
3, preparation (4Z, 6E)-4,6-11 carbon diene Glycol Acetal
The material of reaction is when operated the 3rd step with embodiment 1, the situation of different catalysts, solvent, temperature of reaction such as following table:
| Embodiment | Coupling reagent | Catalyzer | Solvent | Temperature of reaction (℃) | Reaction times (h) | Reaction yield (%) |
| 4 5 6 7 8 9 | Bromine normal-butyl magnesium bromine normal-butyl magnesium bromine normal-butyl magnesium butyllithium butyllithium butyllithium | Pd(PPh 3) 4 Pd(PPh 3) 4 Pd(PPh 3)Cl 2 Pd(PPh 3) 4 Pd(PPh 3) 4 Pd(PPh 3) 4 | Benzene tetrahydrofuran (THF) ether benzene tetrahydrofuran (THF) | 20 40 10 20 40 10 | 20 20 12 20 50 8 | 71 65 56.0 5 30 32 |
4, preparation (4Z, 6E)-4, the 6-undecadienal
Operation implemented for 1 the 4th step with example, different catalytic conditions and the situation in reaction times such as following table:
| Embodiment | Coupling reagent | Catalyzer | Temperature of reaction (℃) | Reaction times (min) | Reaction yield (%) |
| 4 5 6 7 8 9 | H 2O(100ml) H 2O(100ml) H 2O(80ml) H 2O(50ml) H 2O(20ml) H 2O(40ml) | Hydrochloric acid (1ml) hydrochloric acid (0.5ml) acetic acid (20ml) acetic acid (50ml) acetic acid (80ml) acetic acid (60ml) | 40 60 20 40 60 80 | 20 40 120 180 240 180 | 60 68 54 65 94 70 |
5, the preparation (E/Z)-methoxyl group (5Z, 7E)-1,5,7-12 carbon triolefins
Material is when operated the 5th step with embodiment 1, the situation in Different Alkali and reaction times such as following table:
| Embodiment | Alkali | Reaction medium | Temperature of reaction (℃) | Reaction times (h) | Reaction yield (%) |
| 4 5 6 7 8 9 | Sodium ethylate sodium ethylate potassium tert.-butoxide potassium tert.-butoxide potassium tert.-butoxide potassium tert.-butoxide | Ether ether ether tetrahydrofuran (THF) tetrahydrofuran (THF) tetrahydrofuran (THF) | 10 30 10 20 50 40 | 12 20 20 10 20 15 | 55 64 71 70 62 65 |
6, preparation (5Z, 7E)-5,7-12 carbon two olefine aldehydrs
Reaction conditions and operation are with the 6th step of embodiment 1, and differential responses condition feelings are as follows:
| Embodiment | Reaction medium | Temperature of reaction (℃) | Reaction times (h) | Reaction yield (%) |
| 4 5 6 7 8 9 | Acetic acid-oxolane-water (4: 1: 1) acetic acid-oxolane-water (4: 1: 1) acetic acid-oxolane-water (4: 1: 1) perchloric acid-ether-water (1: 1: 1) perchloric acid-ether-water (1: 1: 1) perchloric acid-ether-water (1: 1: 1) | 40 60 80 40 60 80 | 20 17 12 12 10 8 | 81 76 68 47 41 43 |
7, (5Z, 7E)-5, the preparation of 7-Pherocon CM
Material is when operated the 7th step with embodiment 1, the situation in different solvents and reaction times such as following table:
| Embodiment | Reductive agent | Solvent | Reaction times (h) | Reaction yield (%) |
| 4 5 6 7 8 9 | Sodium borohydride sodium borohydride sodium borohydride sodium borohydride sodium borohydride sodium borohydride | Methyl alcohol methyl alcohol methanol ethanol ethanol | 4 6 8 6 7 8 | 71 73 70 68 65 60 |
8, (5Z, 7E)-5, (5Z, 7E)-5,7-12 carbon diene esters together for 7-12 carbon diene esters and propionic acid for 9 steps preparation acetate
The 8th, 9 steps of embodiment 1.
Claims (14)
1. the synthetic method of a pine moth pheromone, it is characterized in that adopting acetylene and propenal is starting raw material, preparation compound 7-bromo under the catalysis of Pd salt-(4Z, 6E)-4, the 6-heptadienal; With its after ethylene glycol protection, obtain compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal, then under Pd catalysis with the coupling of organometallic compound reagent obtain compound (4Z, 6E)-4,6-11 carbon diene Glycol Acetal; Will (4Z, 6E)-4,6-11 carbon diene Glycol Acetal hydrolysis under acidic conditions obtain key intermediate (4Z, 6E)-4, the 6-undecadienal, through Wittig reaction obtain compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5,7-12 carbon triolefins, again its hydrolysis under acidic conditions is obtained compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs are used NaBH at last
4Or KBH
4With its reduction obtain target product (5Z, 7E)-5,7-12 carbon diene-1-alcohol.
2. synthetic method according to claim 1, it is characterized in that compound (5Z, 7E)-5,7-12 carbon diene-1-alcohol through esterification make acetate (5Z, 7E)-5,7-12 carbon diene esters, propionic acid (5Z, 7E)-5,7-12 carbon diene esters.
3. synthetic method according to claim 1, it is characterized in that compound 7-bromo-(4Z, 6E)-4,6-heptadiene Glycol Acetal obtains compound (4Z with the organometallic compound coupling under Pd catalysis, 6E)-4, during 6-11 carbon diene Glycol Acetal, used catalyzer is Pd (PPh
3)
4Or PdCl
2-PPh
3Or Pd (PPh
3)
2Cl
2, used organometallic compound is butyl Grignard reagent or butyllithium, solvent is benzene or tetrahydrofuran (THF) or ether.
4. according to claim 1 or 3 described synthetic methods, it is characterized in that compound (4Z, 6E)-4,6-11 carbon diene Glycol Acetal hydrolysis under acidic conditions obtain key intermediate (4Z, 6E)-4, during the 6-undecadienal, used reaction conditions is: make solvent and exchanger with acetone or butanone or ether or tetrahydrofuran (THF), come catalyzed reaction with sulfuric acid or hydrochloric acid, refluxed 20～40 minutes; Or make solvent with tetrahydrofuran (THF), 5～10% hydrochloric acid catalysis reaction was reacted under the room temperature 8～50 hours; Or in 50～80%HOAc, reacted 2～4 hours down at 10～80 ℃.
5. according to claim 1 or 3 described synthetic methods, it is characterized in that (4Z, 6E)-4, the 6-undecadienal obtains through the Wittig reaction that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, during 7-12 carbon triolefins, Wittig reagent is Ph3P to compound
+CH
2OCH
3Cl
-, reaction medium is an anhydrous diethyl ether, temperature of reaction is 10～80 ℃.
6. synthetic method according to claim 5 is characterized in that preparing Ph3P
+CH
2OCH
3Cl
-Used alkali is t-BuOK, NaOEt.
7. synthetic method according to claim 4 is characterized in that (4Z, 6E)-4, the 6-undecadienal obtains through Wittig reaction that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, during 7-12 carbon triolefins, Wittig reagent is Ph3P to compound
+CH
2OCH
3Cl
-, reaction medium is anhydrous diethyl ether or tetrahydrofuran (THF), temperature of reaction is 10 ~ 50 ℃.
8. synthetic method according to claim 7 is characterized in that preparing Ph3P
+CH
2OCH
3Cl
-Used alkali is t-BuOK, NaOEt.
9, according to claim 1 or 3 described synthetic methods, it is characterized in that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, the hydrolysis under acidic conditions of 7-12 carbon triolefins obtain compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs, used reaction conditions is: acetate-tetrahydrofuran (THF)-water or perchloric acid-ether-water, temperature of reaction are 10～80 ℃.
10, synthetic method according to claim 4, it is characterized in that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, the hydrolysis under acidic conditions of 7-12 carbon triolefins obtain compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs, used reaction conditions is: acetate-tetrahydrofuran (THF)-water or perchloric acid-ether-water, temperature of reaction are 10～80 ℃.
11, synthetic method according to claim 5, it is characterized in that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, the hydrolysis under acidic conditions of 7-12 carbon triolefins obtains compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs, used reaction conditions is: acetate-tetrahydrofuran (THF)-water or perchloric acid-ether-water.
12, synthetic method according to claim 6, it is characterized in that compound (E/Z)-1-methoxyl group-(5Z, 7E)-1,5, the hydrolysis under acidic conditions of 7-12 carbon triolefins obtain compound (5Z, 7E)-5,7-12 carbon two olefine aldehydrs, used reaction conditions is: acetate-tetrahydrofuran (THF)-water or perchloric acid-ether-water, temperature of reaction are 10～80 ℃.
13, synthetic method according to claim 3 is characterized in that reaction conditions is Pd (PPh
3)
4, butyl Grignard reagent, benzene, temperature of reaction is 10～40 ℃.
14, synthetic method according to claim 9 is characterized in that its reaction system is acetate-tetrahydrofuran (THF)-water, and temperature of reaction is 10～80 ℃.
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| CN102115425A (en) * | 2009-12-30 | 2011-07-06 | 重庆华邦胜凯制药有限公司 | Straight chain enol and preparation method thereof |
| CN102613177B (en) * | 2011-01-27 | 2014-03-26 | 温州医学院 | Process for synthesizing sex pheromone of pine caterpillar |
| CN107011136B (en) * | 2017-06-01 | 2023-03-03 | 云南博淇科技有限公司 | Synthesis method of trans-4-decenal |
| CN109456182B (en) * | 2018-11-16 | 2020-10-27 | 中国农业大学 | Synthesis of (5Z,7E) -dodeca-5, 7-dien-1-ol and its acetate and propionate |
| CN109699646B (en) * | 2018-12-29 | 2020-12-15 | 云南大学 | Preparation method of rice stem borer pheromone component |
| CN113412835B (en) * | 2021-07-28 | 2023-01-03 | 中捷四方生物科技股份有限公司 | Synthesis method of novel chlamydomonas pheromone component |
| CN114402891B (en) * | 2022-01-24 | 2023-04-25 | 重庆市林业科学研究院 | Planting method for interplanting hawk tea under degenerated pinus massoniana forest |
| JP2023178017A (en) * | 2022-06-03 | 2023-12-14 | 信越化学工業株式会社 | (4z,6e)-4,6-undecadienyl=trimethylacetate and process for preparing (5z,7e)-5,7-dodecadiene compound therefrom |
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