CN1169416A

CN1169416A - Method for synthesizing sex information hormone of bollworm

Info

Publication number: CN1169416A
Application number: CN 96106728
Authority: CN
Inventors: 戴乾圜; 阎红; 张庆荣; 李冬梅
Original assignee: Beijing University of Technology
Current assignee: Dai Qianhuan
Priority date: 1996-07-01
Filing date: 1996-07-01
Publication date: 1998-01-07
Anticipated expiration: 2016-07-01
Also published as: CN1047378C

Abstract

The present invention relates to a synthesis method fo sex-information hormone of cotton bollworm, which is characterized by that it uses ricinus oil as initiation raw material or mares methyl ricinoleate respectively pass through thermal cracking treatment and base catalytic cracking treatment to obtain undeca-10-olefine acid and 10-hydroxycapric acid, then uses the former as raw material and adopts direct reduction or oxidation process to synthesize (Z) -hexadeca-11-olefine aldehyde, and uses the latter as raw material and adopts five steps to synthesize (Z)-hexadeca-9-oleine aldehyde, then the obtained two products are mixed so as to obtain the invented sex-information hormone of cotton bollworm. It possesses the advantages of easily available raw material, mild operation condition and safety process, etc..

Description

Synthetic method of sex pheromone of cotton bollworm

A synthetic method of sex pheromone of cotton bollworm belongs to the technical field of the synthesis of sex pheromone of insects.

The cotton bollworm is the main pest of cotton in cotton areas in China, and after three or forty generations of propagation, the cotton bollworm can generate complete resistance to the existing pesticide, and the most reliable prevention and treatment measure at present is to utilize sex pheromone, namely sex attractant secreted by female cotton bollworm moth to kill male cotton bollworm moth or generate mating block to realize prevention and treatment. The sex pheromone secreted by female bollworm moth is composed of the mixture of (Z) -hexadeca-11-enal and (Z) -hexadeca-9 enal, and its structure is as follows：

(Z) -hexadec-11-enal

The (Z) -hexadeca-9-enal is prepared by the existing internationally-available synthetic method, or raw materials are difficult to obtain, or the method is not easy to operate and is unsafe in process.

The invention aims to provide a synthetic method of cotton bollworm sex pheromone, which takes castor oil as a starting material, has mild operation conditions and higher yield in each step.

The invention is characterized in that: it uses castor oil as raw material, and adopts the known technology to make it pass through or pass through respectivelyMethyl ricinoleate is subjected to thermal cracking and alkali catalytic cracking respectively to prepare undecyl-10-olefine acid and 10-hydroxydecanoic acid, then (Z) -hexadec-11-olefine aldehyde is synthesized by taking the undecyl-10-olefine acid as a raw material, and (Z) -hexadec-9-olefine aldehyde is synthesized by taking the 10-hydroxydecanoic acid as a raw material, and then the raw materials and the raw material are mixed to obtain the compound, wherein the synthesis steps of the hexadec-11-olefine aldehyde and the hexadec-9-olefine aldehyde are as follows (1) (Z) -hexadec-11-olefine aldehyde synthesis step, ① the undecyl-10-olefine acid reacts with hydrogen bromide under the action of illumination or peroxide to generate 11-bromoundecanoic acid: ② 11, esterifying 11-bromo-undecanoic acidwith methanol to generate 11-bromo-methyl undecanoate; ③ 11 methyl bromoundecanoate reacts with triphenylphosphine to form a quaternary phosphonium salt, which reacts with valeraldehyde to form methyl hexadec-11-enoate, which is a mixture of (Z) -hexadec-11-enoate as the main component but a small amount of (E) -hexadec-11-enoate:

④ reducing hexadec-11-olefine acid methyl ester with lithium aluminum tetrahydride to obtain hexadec-11-enol, wherein the ratio of (Z) -hexadec-11-olefine alcohol and (E) -hexadec-11-enol is the same as that of hexadec-11-olefine acid methyl ester, and oxidizing the hexadec-11-enol with chromic oxide-pyridine reagent to obtain hexadec-11-olefine aldehyde: or ⑤ methyl hexadeca-11-enoate with borane sulfideSelective reduction of the complex leads directly to hexadec-11-enal, which, since all reactions are free from isomer conversion, has a constant ratio between the (Z)/(E) formulae: (2) the synthesis step of (Z) -hexadec-9-enal comprises the reaction of ① 10-hydroxydecanoic acid and acetic anhydride to obtain 10-acetoxydecanoic acid: ② 10-acetoxy decanoic acid reacts with silver oxide or mercuric oxide to form salt through Hunsdiecker-Kochi-Barton reaction, and then reacts with bromine under illumination to obtain 1-bromine-9-acetoxy nonane: ③ 1 the quaternary phosphonium salt is formed by 1-bromo-9-acetoxynonane and triphenylphosphine, then it reacts with heptanal to form 1-acetoxy-hexadeca-9-enol, which is a mixture mainly comprising (Z) -1-acetoxy-hexadeca-9-enol and containing a small amount of (E) -1-acetoxy-hexadeca-9-enol, and the mixture is treated with LiAlH₄Reduction gives hexadec-9-enol with unchanged isomer composition: ④ 1 Deethoxylation of 1-acetoxy-hexadec-9-enol with aluminum tetrachloride to give hexadec-9-enol wherein the ratio between (Z) -and (E) -is the same as in 1-acetoxy-hexadec-9-enol;⑤ oxidizing the hexadec-9-enol with a chromia-pyridine reagent to obtain another target product, hexadec-9-enol, having the same ratio between (Z) -formula and (E) -formula as in 1-acetoxy-hexadec-9-enol: wherein the purification of the respective (Z) -isomer and the removal of the (E) -isomer in the hexadeca-11-enol, the hexadeca-11-enal and the 1-acetoxy-hexadeca-9-enol, the hexadeca-9-enol and the hexadeca-9-enal are carried out by means of column chromatography separation using silica gel treated with copper salt to form silver salt or active aluminum as packing material, so that the (E) -form is eluted first to obtain the completely pure (Z) -form and a small amount of impure (E) -form containing the (Z) -form, and then in the presence of a sensitizer acetophenone, irradiating the impure (E) -form with ultraviolet light to convert it into (Z) -form containing a small amount of (E) -form, the impure product of formula (Z) is then fed to the process cycle of the separation process described above.

Experiments prove that: the cotton bollworm sex pheromone prepared by mixing (Z) -hexadecane-11-olefine aldehyde and (Z) -hexadecane-9-olefine aldehyde which are prepared by using castor oil as an initial raw material has the same structure with two natural effective components secreted by female cotton bollworm moths.

Example (b): 1. the preparation of undec-10-enoic acid and 10-hydroxydecanoic acid from castor oil was slightly modified using well known techniques:

100 g of castor oil, 20 g of methanol and 0.5 g of phosphoric acid are added, heated under reflux for 4 hours, and the glycerol and excess methanol are washed off with water to give 102 g of crude methyl ricinoleate for further preparation.

50 g of castor oil or 50 g of crude methyl ricinoleate are thermally cracked by heating to 400 ℃ and are first distilled off at 153 ℃ to give heptanal, the former giving 1.1 g of heptanal and the latter 5.1 g of heptanal. The reactor was cooled slightly, the pressure was reduced to 15 mm Hg, and undecylenic acid was distilled off at 165 ℃ to give 1.8 g in the former and 8.3 g in the latter. The refined heptanal is colorless liquid with b.p.152.8 ℃,D₄ ¹⁵0.8216，n_D ²⁰1.4257. refined undecylenic acid 10-m.p.24.5 deg.C, b.p.137 deg.C (2 mm Hg), D²⁴ ₄0.9072，n²⁵ _D1.4486。

20 ml of 40 percent caustic soda concentrated solution is added with 20 ml of 2-octanol, the solution is heated to 150 ℃ under stirring, 50 g of castor oil or the mixed solution of 50 g of methyl ricinoleate and 20 ml of 2-octanol is dripped into the solution, the solution is stirred and refluxed for 10 hours, cooled, added with water and acidified by hydrochloric acid, the solid is washed by water and added with petroleum ether to separate out 10-hydroxydecanoic acid, the 10-hydroxydecanoic acid is recrystallized by benzene, the former obtains 3 g of the benzene and the latter obtains 12 g of pure 10-hydroxydecanoic acid m.p.75.5-76.5 ℃, in addition, if the former 2-octanol is recovered, the 2 g can be increased, and the latter adds 8 g of 2.hexadeca-11-olefine aldehyde for synthesis, wherein the synthesis can be directly reduced or oxidized, and the direct reduction synthesis is (1) ① for preparing 11-bromoundecanoic acid by using undecenoic acid:

26.72 g of undecylenic acid and 1.75 g of benzoyl peroxide are dissolved in n-hexane, HBr gas is introduced,the reaction is carried out for half an hour (or the illumination is carried out for 4 hours without peroxide), after the solvent is removed by evaporation, the solid is recrystallized by acetone to obtain 30 g of white crystals, the melting point is 52-52.5 ℃, and the yield is 78%. IR (cm)^-1Neat) 3200(OH), 3010(C ═ C-H), 1680(C ═ O), 690(C ═ C), elemental analysis: theoretical C49.64%, H7.90%, experimental C49.78%, H7.77%, ② preparation of methyl 11-bromoundecanoate from 11-bromoundecanoic acid:

50 ml of methanol, 0.5 ml of sulfuric acid and 10 ml of chloroform are added into 26.6 g of the undecyl bromoundecanoic acid, reflux reaction is carried out under a water separator, and after the reaction is finished, neutralization, water washing and reduced pressure distillation are carried out. The boiling point is 158-159 ℃/6 mm Hg. The colorless liquid collected was 26.5 g, yield 95%. Elemental analysis: theoretical value C51.45%, H8.22%; experimental values C51.50%, H8.31%. IR (cm)^-1Neat) 1730(C ═ O), 1230, 1045, ③ preparation of methyl hexadec-11-enoate from methyl 11-bromoundecanoate:

2.8 g of methyl 11-bromoundecanoate and 2.62 g of triphenylphosphine are refluxed in toluene overnight, and the solid obtained after evaporation of toluene is dissolved in 20 ml of DMF and then 0.1 g of dicyclohexyl- [18]dicyclohexyl]Crown Ether and 1 g K₂CO₃In the presence of the solvent, 0.9 g of valeraldehyde was added dropwise, the reaction was carried out for 3 hours, filtration was carried out, the solvent was distilled off, and the resulting product was treated with a silica gel column to obtain 2.30 g of an oily liquid, which was 93: 7 in terms of (2)/(E) and 86% in terms of yield, elemental analysis showed that theoretical values ofC76.12% and H11.94% and experimental values of C76.27% and H12.01% and ④ were carried out for direct reduction synthesis of hexadec-11-enal from methyl 11-bromoundecanoate:

2.7 g of methyl 11-bromoundecanoate are dissolved in 10 ml of THF and, with stirring at room temperature, 10 ml of 2, 3-dimethyl-2-butylchloroborane disulfide (prepared by the method of Brown et al, see Fieser, supra) are added&Fieser, vol 12, page 485) in THF solution and reacted for half an hour. Adding water, acidifying, extracting with diethyl ether, drying the extractive solution, and evaporating. Separating and purifying by column chromatography. The oily product was 2.15 g, yield 90%. Elemental analysis: theoretical value C48.42%, H8.40%; the experimental values are C48.29% and H8.31%. IR (cm)^-1Neat) 3010(═ C-H), 2710(HC ═ O), 1730(HC ═ O), 730(C ═ C); ` H-NMR (. delta.ppm) 0.9 (3H)，t，CH₃)，0.3(18H，br.-(CH₂)_n-)，2.0(4H，m，CH₂C＝CCH₂)，2.3(2H，m，-CH₂CHO), 5.35(2H, t, CH ═ CH), 8.9(1H, br. CHO), MS (M/Z, O/O)238(2.21), 220(4.8), 55(71.57), 41(100), (2) oxidative synthesis ① hexadec-11-enoic acid methyl ester from undec-10-enoic acid, procedure as above, ② hexadec-11-enol from hexadec-11-enoic acid methyl ester:

2.7 g of hexadeca-11-enoic acid methyl ester are dissolved in 20 ml of anhydrous ether and 0.7 g of LiAlH are gradually added dropwise with stirring₄Dissolving in 100 ml of diethyl ether, refluxing for 4 hr, decomposing with ice water, dissolving the precipitated alumina with 50% sulfuric acid, washing the ether layer with water, and MgSO₄Drying gave a pale yellow liquid which was purified by column chromatography to give 2.1 g of product in 88% yield. Elemental analysis: theoretical values C80.00%, H13.33%; experimental values C79.91%, H13.16%;③ Hexadecyl-11-enal is obtained from hexadec-11-enol:

7.8 g of pyridine in 100 ml of CH₂Cl₂In the reaction solution, 4.8 g of CrO are added₃Stirred for 15 minutes under ice water, to which CH containing 1.2 g of hexadec-11-enol was added dropwise₂Cl₂Stirring the solution to react for half an hour, pouring out the supernatant, and adding CH₂Cl₂Washing the brownish black solid, and washing the organic layer with dilute hydrochloric acid, NaHCO₃Liquid and water washing, MgSO₄Drying, evaporation of the solvent and purification by column chromatography gave 1.17 g of product in 90% yield. Elemental analysis: theoretical value C80.67%, H12.61%; the experimental values are C80.75% and H12.55%. The IR, NMR and MS were in agreement with those obtained in the direct reduction synthesis example. 3. Synthesis of hexadeca-9-enal: (1) preparation of 10-acetoxydecanoic acid from 10-hydroxydecanoic acid:

1.9 g 10-hydroxy capric acid, 1.6 g pyridine, adding 1.5 g acetic anhydride, reacting in 10 ml ether, evaporating to remove ether, adding water for decomposition, washing with hydrochloric acid and sodium bicarbonate solution, recrystallizing with alcohol to obtain 2.03 g product with 95% yield. m.p.34-35 ℃, b.p.175-176 ℃/3 mm Hg. IR (cm)^-1Clean) 1740, 1710(C ═ O), 1240, 1075 (CH)₃COO)；′H-NMR(δppm)0.89(16H，Br，-(CH₂)₈-)，2.04(3H，s，COCH₃)，2.34(2H，t，-CH₂COO)，4.05(2H，-OCH₂-), 11.6(1H, s, -COOH); (2) preparation of acetate of 9-bromononanol from 10-acetoxydecanoic acid:

2.14 g of 10-acetoxydecanoic acid in 40 ml of CH₂Cl₂Adding anhydrous magnesium sulfate 1.4 g and mercuric oxide 3.02 g, stirring, refluxing, and dripping bromine 0.7 ml in CH 20 ml under illumination₂Cl₂Refluxing the solution for 2 hr to colorless, cooling and filtering, and using NaHCOas organic layer₃Liquid and water washing, MgSO₄After drying and evaporation of the solvent, the oily product obtained after column chromatography was 2.18 g, 82% yield. IR (cm)^-1Net) 1740(CO), 1240, 1035 (CH)₃COO)；′H-NMR(δppm)1.32(14H，Br，-(CH₂)₇-)，2.04(3H，s，COCH₃)，3.33(2H，-CH₂-Br)，4.05(2H，t，-CH₂O-), MS (M/Z%) 264 (0.5); (3) preparation of the acetate of hexadec-9-enol from the acetate of 9-bromononanol:

2.66 g of 9-bromononanol acetate, i.e.acetic acid-9-nonanol ester, 2.62 g of triphenylphosphine and 1.0 g of heptanal, 2.45 g of an oily liquid are obtained by refining on silica gel in the procedure described above for the preparation of hexadeca-11-enoic acid carboxylic acid from methyl 11-bromoundecanoate, yield 87%. The (Z)/(E) -form is 91: 9. Elemental analysis: theoretical value C76.60%, H12.06%; the experimental values are C76.48% and H11.99%. (4) Preparation of hexadec-9-enol from hexadec-9-nonanol ester:

2 g of hexadec-9-enol acetate 50 ml ether solution, 0.5 g of lithium aluminum hydride in 50 ml ice-cooled ether solution was added dropwise and refluxed for 4 hours, after decomposition in cold water, alumina was dissolved in dilute sulfuric acid, the ether layer was washed with water and dried, and the ether was evaporated to obtain 1.5 g of oily substance with a yield of 88%. Elemental analysis: theoretical values C80.00%, H13.33%; experimental values C80.15%, H13.16%; IR (cm)^-1Neat) 3320(OH), 3000(C ═ CH)710(C ═ C); ' H-NMR (delta ppm) 5.16-5.35 (2H, m, -CH ═ CH), 3.35-3.66 (2H, m, OCH)₂-)，2.85(1H，s，OH)，1.7～2.15(4H，m，CH_2c＝CCH₂)，1.2～1.3(24H，m，-(CH₂)_n-)，0.9(3H，t，-CH₃) (ii) a (5) Preparation of hex-9-enal from hex-9-enol:

1.56 g of pyridine, 9.6 g of chromium oxide and 2.4 g of hexadec-9-enol, in the same manner as in the preparation of hexadec-11-enal from hexadec-11-enol, 2.15 g of the product are obtained after purification by column chromatography, the yield being 90%. Wherein, IR (cm)^-1Neat) 3000(C ═ CH), 2700, (H — CO), 1680(C ═ O); ' H-NMR (. delta.ppm) 9.55(1H, s, CHO), 5.2 to 5.3(2H, m, CH ═ CH), 1.6 to 2.5(6H, m, CH)₂C＝CCH₂，-CH₂CO)，1.2～1.3(24H，m，-(CH₂)_n-)，0.9(3H，t，-CH₃). 4. The hexa-11-enal and hexa-9-enal are mixed to obtain the sex pheromone of bollworm.

In addition, in the purification of (Z) -isomer and the removal of (E) -isomer, since no isomerization occurs in the reaction, this purification and removal process is carried out in the preparation of methyl hexadec-11-enoate, hexadec-11-enol, hexadec-11-enal or hexadec-9-enol, hexadec-9-enal, and we can obtain pure (Z) -formula target product. The packing material for column chromatography is silica gel or activated aluminum treated with copper salt or silver salt, eluted with chloroform/petroleum ether, and the (E) -form is first separated from the column, and the (Z) -form is prepared as a completely pure substance, and the (E) -form contains a small amount of the (Z) -form. The impure (E) -form is then fed to the next conversion cycle.

Purification of (Z) -hexadec-9-enol: 100 g of 80-100 mesh silica gel, 200 ml of 2% CuSO₄And (4) treating the solution and performing suction filtration. Drying and activating at 110 ℃.1 g of hexadec-9-enol was dissolved in petroleum ether (Z/E. apprxeq. 91/9) in a 1 m column packed with the stationary phase as above, eluted with chloroform/petroleum ether (1: 3) and detected by gas chromatography. (E) The form (I) first eluted and 0.8 g of (Z) -hexadec-9-enol was finally obtained. 0.10 g of an impure (E) -form was recovered, containing 80% of the(E) -form and 20% of the (Z) -form. Purification of the other (Z) -forms was similar.

(E) When the isomer is converted into the (Z) -isomer, the impure (E) -isomer can be converted into the corresponding (Z) -form body at a conversion rate of 80-100% in the presence of ultraviolet light and a sensitizer such as acetophenone, and then put into the above separation cycle.

(E) -isomerization of hexadec-9-enol: 0.1 g of impure (E) -hexadec-9-enol (containing 20% of (Z) -form) is dissolved in 5 ml of petroleum ether, 0.01 g of acetophenone is added, after ultraviolet light irradiation for half an hour, the solvent is evaporated off to obtain 0.1 g of (Z) -hexadec-9-enol (gas chromatography analysis, wherein the content of (E) -form is 0-5%). The above separate cycles can be put into use, if necessary.

The transformation of the other (E) -forms is similar.

The above tests demonstrate that: the sex pheromone of cotton bollworm prepared by the method of the invention shows strong sexual attraction effect to male cotton bollworm moth.

Claims

1. A synthetic method of bollworm sex pheromone is prepared by mixing (Z) -hexadeca-11-olefine aldehyde and (Z) -hexadeca-9-olefine aldehyde, and is characterized in that castor oil is used as a starting material, and is respectively subjected to thermal cracking and alkali catalytic cracking to prepare undec-10-olefine acid and 10-hydroxydecanoic acid, then the undec-10-olefine acid is used as a raw material to synthesize (Z) -hexadeca-11-dilute aldehyde, the 10-hydroxydecanoic acid is used as a raw material to synthesize (Z) -hexadeca-9-olefine aldehyde, and then the (Z) -hexadeca-11-olefine aldehyde and the-hexadeca-9-olefine aldehyde are mixed, wherein the following synthetic steps of the hexadeca-11-olefinealdehyde and the-the hexadeca-11-olefine aldehyde are respectively as follows (1), namely, the synthetic step of ①, the undec-10-olefine acid is reacted with hydrogen bromide under the action of light or peroxide to generate the 11-bromoundecanoic acid: ② 11, esterifying 11-bromo-undecanoic acid with methanol to generate 11-bromo-methyl undecanoate; ③ 11 methyl bromoundecanoate reacts with triphenylphosphine to form a quaternary phosphonium salt, which reacts with valeraldehyde to form methyl hexadec-11-enoate, which is a mixture of (Z) -hexadec-11-enoate as the main component but a small amount of (E) -hexadec-11-enoate:

④ Hexahex-11-enoic acid methyl ester is reduced with lithium aluminum tetrahydrideThe hexadec-11-enol is obtained in the same ratio of (Z) -hexadec-11-enol to (E) -hexadec-11-enol as the methyl hexadec-11-enoate; then oxidizing the hexadecane-11-enol by using a chromium oxide-pyridine reagent to obtain hexadecane-11-enal: alternatively, ⑤ methyl hexadec-11-enoate can be reduced selectively with borane sulfide complex to directly produce hexadec-11-enal, with the ratio between (Z)/(E) being unchanged since all reactions are without isomer conversion: (2) the synthesis step of (Z) -hexadec-9-enal comprises the reaction of ① 10-hydroxydecanoic acid and acetic anhydride to obtain 10-acetoxydecanoic acid: ② 10-acetoxy decanoic acid reacts with silver oxide or mercuric oxide to form salt through Hunsdiecker-Kochi-Barton reaction, and then reacts with bromine under illumination to obtain 1-bromine-9-acetoxy nonane: ③ 1 the quaternary phosphonium salt is generated by reacting 1-bromo-9-acetoxynonane with triphenylphosphine and then Wittig reaction with heptanal to generate 1-acetoxy-hexadeca-9-enol, which is a mixture mainly comprising (Z) -1-acetoxy-hexadeca-9-enol and containing a small amount of (E) -1-acetoxy-hexadeca-9-enol, and using LiAlH₄Reduction gives hexadec-9-enol with unchanged isomer composition: ④ 1 Deethoxylation of 1-acetoxy-hexadec-9-enol with aluminum tetrachloride to give hexadec-9-enol wherein the ratio between (Z) -and (E) -is the same as in 1-acetoxy-hexadec-9-enol, ⑤ further oxidation of the hexadec-9-enol with chromic oxide-pyridine reagent gives another desired product hexadec-9-enal wherein the ratio between (Z) -and (E) -is the same as in 1-acetoxy-hexadec-9-enol:

2. the method for synthesizing sex pheromone of Heliothis armigera according to claim 1, which comprises the following steps: wherein the purification of the respective (Z) -isomer and the removal of the (E) -isomer in the hexadeca-11-enol, the hexadeca-11-enal and the 1-acetoxy-hexadeca-9-enol, the hexadeca-9-enol and the hexadeca-9-enal are carried out by means of column chromatography separation using silica gel treated with copper salt to form silver salt or active aluminum as packing material, so that the (E) -form is eluted first to obtain the completely pure (2) -form and a small amount of impure (E) -form containing the (Z) -form, and then in the presence of a sensitizer acetophenone, irradiating the impure (E) -form with ultraviolet light to convert it into (Z) -form containing a small amount of (F) -form, the impure product of formula (Z) is then fed to the process cycle of the separation process described above.