CN109678818B - Method for synthesizing aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of taurus communis - Google Patents

Method for synthesizing aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of taurus communis Download PDF

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CN109678818B
CN109678818B CN201910033781.7A CN201910033781A CN109678818B CN 109678818 B CN109678818 B CN 109678818B CN 201910033781 A CN201910033781 A CN 201910033781A CN 109678818 B CN109678818 B CN 109678818B
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pyran
cis
nonenal
epoxy
tetrahydro
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CN109678818A (en
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何佳怡
陈志立
赵帅
夏冉
吴林盛
侯苏童
周骏涛
陈新
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Jiangsu Ninglu Technology Co.,Ltd.
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Nimord Inc
Changzhou University
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    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
    • C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D301/00—Preparation of oxiranes
    • C07D301/02—Synthesis of the oxirane ring
    • C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
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Abstract

The invention relates to a method for synthesizing aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of a taurus communis, belonging to the field of medicine synthesis. 1, 4-butanediol is taken as a raw material, firstly DHP is used for single protection of diol, and then TEMPO is used for oxidation to obtain 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde; then carrying out Wittig reaction to obtain (Z) -2- (hept-4-ene-1-oxyl) tetrahydro-2H-pyran; then removing DHP protection, and oxidizing TEMPO to obtain (Z) -4-heptenal; then carrying out Wittig reaction to obtain (2E,6Z) -nona-2, 6-dienal; finally, epoxidation is carried out to obtain the aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of the pink-neck longicorn. The overall yield was 6.5%. The method takes the cheap 1, 4-butanediol as the starting material, has simple operation and mild condition, and is suitable for large-scale preparation.

Description

Method for synthesizing aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of taurus communis
Technical Field
The invention relates to a novel synthesis method of a natural product pheromone component, in particular to a synthesis method of aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of Aromia bungi of Tanaemon hongkongensis, which has insect attraction and no toxicity or harm and belongs to the field of drug synthesis.
Background
Aromia bungi (Coleoptera: Tinosporaceae) is a wood beetle native to the east of China, Korea, Mongolia and Russia. Recently, the gene has invaded countries such as Japan, Italy, Germany, and is also found in countries such as the United states, the British, Australia, and the like. It mainly parasitizes trees of the genus Prunus, including some economic fruit trees such as cherry, peach, plum and apricot trees. It is one of the only four species worldwide. As with many pelargonium beetles, developing larvae feed on the nutrient-rich phloem, cambium and outer sapwood, and overwinter as larvae, sometimes for several years. Mature larvae bore into the xylem to form a pupation chamber, with day and night active adults emerging from mid-summer. Damage to vascular tissue and weakening of the trunk and branches by the larval tunnels often kills the host tree. Because the developing larvae are hidden in the subcortical tissues of the host, the beetles are difficult to control by pesticides, and the development of biological control technology for controlling pests such as insect pheromones is urgently needed, so that the beetle has the advantages of strong speciality, no public nuisance, no natural enemies, environmental protection and the like, and the beetle is increasingly concerned about research and application at home and abroad and is successfully applied to the control of various agricultural and forestry pests.
In 12 months 2017, Millar et al identified and synthesized the male-produced aggregative pheromone (E) -cis-6,7-epoxy-2-nonenal (1) of a. bungii, which was synthesized directly by epoxidation of violacein and was biologically active, attracting both sexes in field trials conducted in china and japan. However, the raw materials are expensive and not suitable for industrial production (T.xu, et al.identification of a large-produced sex-aggregation photomonodor a high hly innovative gastric beer, Aramia Bungi scientific Reports,2017,7, 7330).
In 2018, Kenji Mori et al started from cis-2-pentenol, introduced chirality by Sharpless asymmetric epoxidation, and chain extension by Grignard coupling and olefin cross metathesis, to finally obtain (E) -cis-6,7-epoxy-2-nonenal (1) as two enantiomers in 4.7% yield. The raw materials are expensive, the conditions are harsh, and the industrial production is not suitable (K.Mori. Phomopone Synthesis. part 263: Synthesis of the rare and macromolecular oligomers of (E) -cis-6,7-epoxy-2-nonenal, the large-reduced phenoxy soft-connected long ether, Aromia Bunge ii. tetrahedron,2018,74, 1444-.
Disclosure of Invention
The invention provides a novel synthesis method of aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of Aromianbubingii of peach red neck longicorn in order to overcome the defects in the prior art, which takes cheap and easily obtained 1, 4-butanediol as a starting material to carry out seven-step reaction, has the total yield of 6.5 percent, is simple to operate, has mild conditions and is suitable for large-scale preparation. In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
(1) under the action of acid, 1, 4-butanediol and 3, 4-dihydro-2H-pyran are in a mixed solvent of tetrahydrofuran and dichloromethane to generate 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol;
wherein the acid is pyridinium p-toluenesulfonate or p-toluenesulfonic acid monohydrate, preferably p-toluenesulfonic acid monohydrate; the volume ratio of the tetrahydrofuran to the dichloromethane is 1: 10; wherein the molar ratio of 3, 4-dihydro-2H-pyran to 1, 4-butanediol is 1:1 to 1.5, preferably 1: 1.2.
(2) Oxidizing the 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol obtained in the step (1) with TEMPO and iodobenzene diacetate in dichloromethane to generate 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde;
wherein the molar ratio of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol to TEMPO is 1:0.05-0.2, preferably 1: 0.1; the molar ratio of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol to iodobenzene diacetate is 1:1-2, preferably 1: 1.5.
(3) In a low-temperature nitrogen atmosphere, generating (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran from the 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde obtained in the step (2) and n-propyltriphenyl phosphonium bromide salt and alkali in a tetrahydrofuran solution;
wherein the low temperature is-100-50 ℃, the alkali is potassium tert-butoxide, LHMDS or KHMDS, preferably KHMDS, and the solvent is anhydrous tetrahydrofuran.
(4) Reacting the (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran obtained in the step (3) in a solvent under the action of an acid to generate (Z) -4-hepten-1-ol;
wherein the acid is 10% by mass of HCl, pyridinium p-toluenesulfonate or p-toluenesulfonate monohydrate, preferably p-toluenesulfonate monohydrate, the molar ratio of the acid to (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran is 1:10, and the solvent is methanol or ethanol, preferably methanol.
(5) Oxidizing the (Z) -4-hepten-1-ol obtained in the step (4) with TEMPO and iodobenzene diacetate in dichloromethane to generate (Z) -4-heptenal;
wherein the molar ratio of (Z) -4-hepten-1-ol to TEMPO is from 1:0.05 to 0.2, preferably 1: 0.1; the molar ratio of the (Z) -4-hepten-1-ol (6) to the iodobenzene diacetate is 1:1-2, preferably 1: 1.5.
(6) Reacting the (Z) -4-heptenal obtained in the step (5) with formyl methylene triphenylphosphine in an organic solvent to obtain (2E,6Z) -non-2, 6-dienal;
wherein the solvent is chloroform, dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile or 1, 4-dioxane, preferably 1, 4-dioxane, and the molar ratio of (Z) -4-heptenal to formyl methylene triphenylphosphine is 1:1-3, preferably 1: 1.1.
(7) Epoxidizing the (2E,6Z) -nona-2, 6-dienal obtained in the step (6) with m-chloroperoxybenzoic acid in dichloromethane to generate (E) -cis-6, 7-epoxy-2-nonenal;
wherein the molar ratio of the (2E,6Z) -nona-2, 6-dienal to the m-chloroperoxybenzoic acid is 1:1-2, preferably 1: 1.1.
The synthesis route of the aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of the peach red neck longicorn A.bungi is as follows:
Figure BDA0001945154080000041
compared with the prior art, the invention has the beneficial effects that:
(1) the method takes 1, 4-butanediol as a raw material, firstly uses DHP to singly protect the diol, and then TEMPO is oxidized into 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde; then under the action of KHMDS, carrying out Wittig reaction to obtain (Z) -2- (hept-4-ene-1-yloxy) tetrahydro-2H-pyran; removing DHP protection, and oxidizing TEMPO to obtain (Z) -4-heptenal; then, Wittig reaction is carried out to obtain (2E,6Z) -nona-2, 6-dienal; finally, the aggregation pheromone- (E) -cis-6,7-epoxy-2-nonenal of the pink-neck longicorn is obtained by the epoxidation of MCPBA. The overall yield was 6.5%;
(2) the method for synthesizing the aggregation pheromone of the Taohorma persimilii A.bungi takes the cheap 1, 4-butanediol as the starting raw material, has simple operation, mild condition, insect attraction, no toxicity and no harm, and is suitable for large-scale preparation.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without inventive step, are within the scope of the present invention.
Step 1: preparation of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (3)
Example 1: p-toluenesulfonic acid monohydrate (2.3g,12mmol) was added to a tetrahydrofuran/dichloromethane mixed solution (220mL) of 1, 4-butanediol (13.0g,144mmol), cooled to 0 ℃ and then 3, 4-dihydro-2H-pyran (10.8mL,120mmol) was added dropwise and stirred at room temperature for 6H. TLC detection, after the reaction is finished, water quenching is added, dichloromethane extraction is carried out, organic phases are combined, dried by anhydrous sodium sulfate, reduced pressure concentration is carried out, and column chromatography is carried out to purify colorless liquid 3(15.56g, yield is 75%).1H NMR(400MHz,CDCl3):δ4.53(t,J＝3.5Hz,1H),3.76-3.81(m,1H),3.69-3.73(m,1H),3.57(t,J＝6.0Hz,2H),3.43-3.46(m,1H),3.34-3.37(m,1H),2.98(s,1H),1.72-1.76(m,1H),1.61-1.65(m,5H),1.44-1.53(m,4H)；13C NMR(100MHz,CDCl3):δ99.8,67.5,62.4,62.3,30.6,29.8,26.4,25.3,19.5.
Example 2: pyridine p-toluenesulfonate (0.31g,1.2mmol) was added to a mixed solution (22mL) of 1, 4-butanediol (1.3g,14.4mmol) in tetrahydrofuran and dichloromethane, cooled to 0 ℃ and then 3, 4-dihydro-2H-pyran (1.1mL,12mmol) was added dropwise thereto, followed by stirring at room temperature for 6 hours. TLC detection, after the reaction is finished, water quenching is added, dichloromethane extraction is carried out, organic phases are combined, dried by anhydrous sodium sulfate, decompressed, concentrated and purified by column chromatography to obtain colorless liquid 3(1.5g, yield 70%). Compared with example 1, the p-toluenesulfonic acid monohydrate is changed into the pyridinium p-toluenesulfonic acid, and other conditions are not changed. Of the product1H NMR and13CNMR is identical to example 1.
Example 3: p-toluenesulfonic acid monohydrate (0.23g,12mmol) was added to a tetrahydrofuran dichloromethane mixed solution (22mL) of 1, 4-butanediol (1.08g,12mmol), cooled to 0 ℃ and then 3, 4-dihydro-2H-pyran (1.1mL,12mmol) was added dropwise and stirred at room temperature for 6 hours. TLC detection, after the reaction is finished, water quenching is added, dichloromethane extraction is carried out, organic phases are combined, dried by anhydrous sodium sulfate, decompressed, concentrated and purified by column chromatography to obtain colorless liquid 3(1.3g, yield 62%). The equivalent of 1, 4-butanediol was reduced as compared with example 1, and the other conditions were not changed. Of the product1H NMR and13c NMR was completely in accordance with example 1.
Step 2: preparation of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde (4)
Example 4: TEMPO (1.56g,10mmol) and iodobenzene diacetate (48.3g,150mmol) were added to a solution of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (17.4g,100mmol) in dichloromethane (100mL) respectively and reacted at room temperature for 2H. TLC detection, after the reaction was completed, saturated sodium thiosulfate was added to quench the separated liquid, and then the liquid was washed with saturated sodium bicarbonate and saturated brine, respectively, and after the solvent was recovered, column chromatography was performed to purify the resulting product to obtain colorless liquid 4(12.7g, 78%).1H NMR(400MHz,CDCl3):δ9.79(d,J＝1.36Hz,1H),4.57(s,1H),3.75-3.85(m,2H),3.49-3.51(m,1H),3.41-3.44(m,1H),2.55(t,J＝7.08Hz,2H),1.92-1.99(m,2H),1.78-1.81(m,1H),1.69-1.73(m,1H),1.51-1.58(m,4H)；13C NMR(100MHz,CDCl3):δ202.6,98.9,66.5,62.4,41.2,30.7,25.5,22.7,19.6.
Example 5: TEMPO (0.16g,1mmol) and iodobenzene diacetate (3.54g,11mmol) were added to a solution of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (1.74g,10mmol) in dichloromethane (10mL) respectively and reacted at room temperature for 4H. TLC detection, after the reaction was completed, saturated sodium thiosulfate was added to quench the separated liquid, and then the liquid was washed with saturated sodium bicarbonate and saturated brine, respectively, and after the solvent was recovered, column chromatography was performed to purify the resulting product to obtain colorless liquid 4(1.03g, 60%). The equivalent of iodobenzene diacetate was reduced compared to example 4, and the other conditions were unchanged. Of the product1H NMR and13c NMR and implementationExample 4 is identical.
Example 6: TEMPO (0.16g,1mmol) and iodobenzene diacetate (6.44g,20mmol) were added to a solution of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (1.74g,10mmol) in dichloromethane (10mL) respectively and reacted at room temperature for 1.5H. TLC detection, after the reaction was completed, the separated solution was quenched by addition of saturated sodium thiosulfate, washed with saturated sodium bicarbonate and saturated brine, respectively, and the solvent was recovered and purified by column chromatography to give colorless liquid 4(1.37g, 80%). The equivalent of iodobenzene diacetate was increased compared to example 4, and the other conditions were unchanged. Of the product1H NMR and13c NMR was in full agreement with example 4.
Example 7: TEMPO (0.08g,0.5mmol) and iodobenzene diacetate (4.83g,15mmol) were added to a solution of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (1.74g,10mmol) in dichloromethane (10mL) respectively and reacted at room temperature for 6H. TLC detection, after the reaction was completed, saturated sodium thiosulfate was added to quench the separated liquid, and then the liquid was washed with saturated sodium bicarbonate and saturated brine, respectively, and after the solvent was recovered, column chromatography was performed to purify the resulting product to obtain colorless liquid 4(1.12g, 65%). The equivalent of TEMPO is reduced compared to example 4, the other conditions being unchanged. Of the product1H NMR and13c NMR was in full agreement with example 4.
Example 8: TEMPO (0.32g,2mmol) and iodobenzene diacetate (4.83g,15mmol) were added to a solution of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol (1.74g,10mmol) in dichloromethane (10mL) respectively and reacted at room temperature for 1H. TLC detection, after the reaction was completed, the separated solution was quenched with saturated sodium thiosulfate, washed with saturated sodium bicarbonate and saturated brine, respectively, and the solvent was recovered and purified by column chromatography to obtain colorless liquid 4(1.36g, 79%). The equivalent of TEMPO is increased compared to example 4, with the other conditions being unchanged. Of the product1H NMR and13c NMR was in full agreement with example 4.
Step 3 preparation of (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran (5)
Example 9: to a suspension (70ml) of n-propyltriphenylphosphine bromide (29.3g,76.2mmol) in anhydrous tetrahydrofuran at-78 deg.C under nitrogen, KHMDS freeAfter stirring a solution of tetrahydrofuran in water (64.5mL,64.5mol,1.0mol/L) at the same temperature for 1 hour, a solution of Compound 4(10.1g,58.6mmol) in anhydrous tetrahydrofuran (20mL) was added dropwise, and the mixture was allowed to stand at room temperature for 18 hours after 10 minutes. The reaction was transferred to an ice bath, quenched by addition of saturated ammonium chloride solution, and after recovery of tetrahydrofuran, extracted with ethyl acetate (3 × 100mL), the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to give product 5(7.6g, 76%) as a yellow oily liquid.1H NMR(400MHz,CDCl3):δ5.32-5.41(m,2H),4.58(t,J＝3.48Hz,1H),3.85-3.91(m,1H),3.72-3.78(m,1H),3.48-3.53(m,1H),3.37-3.42(m,1H),2.03-2.14(m,4H),1.83-1.86(m,1H),1.53-1.72(m,7H),0.96(t,J＝7.54Hz,3H)；13C NMR(100MHz,CDCl3):δ132.2,128.5,98.9,67.1,62.4,30.9,29.9,25.6,13.8,20.6,19.8,14.4.
Example 10: to an anhydrous tetrahydrofuran suspension (2mL) of n-propyltriphenylphosphine bromide (1.0g,2.6mmol) was added dropwise a solution of KHMDS in anhydrous tetrahydrofuran (2mL, 2.2mol,1.0mol/L inTHF) under a nitrogen atmosphere at-50 deg.C, and after stirring at the same temperature for 1 hour, a solution of Compound 5(0.35g,2mmol) in anhydrous tetrahydrofuran (2mL) was added dropwise, and after 10min, the mixture was allowed to cool to room temperature and reacted for 18 hours. The reaction was transferred to an ice bath, quenched by addition of saturated ammonium chloride solution, and after recovery of tetrahydrofuran, extracted with ethyl acetate (3 × 5mL), the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to give product 5(0.2g, 51%) as a yellow oily liquid. The temperature was increased compared to example 9, and the other conditions were unchanged. Of the product1H NMR and13c NMR was in full agreement with example 9.
Example 11: to an anhydrous tetrahydrofuran suspension (2mL) of n-propyltriphenylphosphine bromide (1.0g,2.6mmol) was added dropwise a solution of potassium tert-butoxide in anhydrous tetrahydrofuran (2mL), followed by stirring at the same temperature for 1 hour, followed by addition of a solution of compound 5(0.35g,2mmol) in anhydrous tetrahydrofuran (2mL), and after 10 minutes, the mixture was allowed to cool to room temperature for 18 hours. The reaction was transferred to an ice bath, quenched by addition of saturated ammonium chloride solution, recovered tetrahydrofuran, extracted with ethyl acetate (3 × 5mL), combinedThe organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to give product 5(0.24g, 60%) as a yellow oily liquid. Compared with example 9, the alkali is changed into potassium tert-butoxide, and other conditions are not changed. Of the product1H NMR and13c NMR was in full agreement with example 9.
Example 12: to a suspension (2mL) of n-propyltriphenylphosphine bromide (1.0g,2.6mmol) in anhydrous tetrahydrofuran was added dropwise a solution of LiHMDS in anhydrous tetrahydrofuran (2mL), followed by stirring at the same temperature for 1 hour, followed by addition of a solution of Compound 5(0.35g,2mmol) in anhydrous tetrahydrofuran (2mL), and after 10 minutes, the mixture was allowed to cool to room temperature for 18 hours. The reaction was transferred to an ice bath, quenched by addition of saturated ammonium chloride solution, and after recovery of tetrahydrofuran, extracted with ethyl acetate (3 × 5mL), the organic phases were combined and washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and subjected to column chromatography to give product 5(0.26g, 65%) as a yellow oily liquid. Compared with example 9, the alkali was changed to LiHMDS, and other conditions were not changed. Of the product1H NMR and13c NMR was in full agreement with example 9.
Step 4 preparation of (Z) -4-hepten-1-ol (6)
EXAMPLE 13 to a solution of compound 5(7.6g,38.5mmol) in methanol (50mL) was added p-toluenesulfonic acid monohydrate (0.74g,3.85mmol), and the mixture was stirred at room temperature for 15 h. After addition of excess sodium bicarbonate, methanol was recovered and purified by column chromatography to give (Z) -4-hepten-1-ol 6(3.3g, 75%.1H NMR(400MHz,CDCl3):δ5.31-5.44(m,2H),3.63(t,J＝6.60Hz,2H),2.34(s,1H),2.03-2.12(m,4H),1.59-1.66(m,2H),0.96(t,J＝7.52Hz,3H)；13CNMR(100MHz,CDCl3):δ132.3,128.3,62.4,32.6,23.5,20.5,14.3.
EXAMPLE 14 to a solution of Compound 5(0.4g,2mmol) in methanol (2mL) was added a 10% HCl solution (2mL) and the mixture was stirred at room temperature for 15 h. After addition of excess sodium bicarbonate, methanol was recovered, diluted with ethyl acetate and extracted, and purified by column chromatography to give (Z) -4-hepten-1-ol 6(0.13g, 56%). Compared with example 13, the acid was changed to a 10% by mass hydrochloric acid solution, and other conditions were not changed. Of the product1H NMR and13c NMR completely agreed with example 13.
EXAMPLE 15 to a solution of Compound 5(0.4g,2mmol) in methanol (2mL) was added pyridinium p-toluenesulfonate (50mg,0.2mmol), and the mixture was stirred at room temperature for 15 h. After addition of excess sodium bicarbonate, methanol was recovered and purified by column chromatography to give (Z) -4-hepten-1-ol 6(0.16g, 70%). Compared with example 13, the acid is changed into pyridinium p-toluenesulfonate, and other conditions are not changed. Of the product1H NMR and13c NMR completely agreed with example 13.
EXAMPLE 16 to an ethanol solution (2mL) of Compound 5(0.4g,2mmol) was added p-toluenesulfonic acid monohydrate (38mg,0.2mmol), and the mixture was stirred at room temperature for 15 h. After addition of excess sodium bicarbonate, methanol was recovered and purified by column chromatography to give (Z) -4-hepten-1-ol 6(0.15, 67%). Compared with the example 13, the solvent methanol is changed into ethanol, and other conditions are not changed. Of the product1H NMR and13c NMR completely agreed with example 13.
Step 5 preparation of (Z) -4-heptenal (7)
EXAMPLE 17 TEMPO (0.48g,2.8mmol) and iodobenzene diacetate (13.5g,42mmol) were added to a solution of (Z) -4-hepten-1-ol (3.2g,28mmol) in dichloromethane (28mL) respectively and reacted at room temperature for 1 h. TLC detection, after the reaction was completed, saturated sodium thiosulfate was added to quench and separate the solution, and then the solution was washed with saturated sodium bicarbonate and saturated brine, respectively, and after the solvent was recovered, column chromatography was performed to purify the solution to obtain colorless liquid 7(2.4g, 77%).1H NMR(400MHz,CDCl3):δ9.77(t,J＝1.58Hz,1H),5.40-5.47(m,1H),5.26-5.33(m,1H),2.47-2.51(m,2H),2.37(dd,J1＝14.4Hz,J2＝7.2Hz,2H),2.06(t,J＝7.44Hz,2H),0.97(t,J＝7.52Hz,3H)；13C NMR(100MHz,CDCl3):δ202.3,133.3,126.5,43.8,20.5,20.0,14.2.
EXAMPLE 18 TEMPO (28mg,0.18mmol) and iodobenzene diacetate (0.62g,1.93mmol) were added to a solution of (Z) -4-hepten-1-ol (0.2g,1.75mmol) in dichloromethane (2mL) respectively and reacted at room temperature for 2 h. TLC detection, gas phase detection after the reaction is finished, and the yield is 60%. The equivalent of iodobenzene diacetate was reduced compared to example 17, and the other conditions were unchanged.
EXAMPLE 19 TEMPO (28mg,0.18mmol) and iodobenzene diacetate (1.13g,3.5mmol) were added to a solution of (Z) -4-hepten-1-ol (0.2g,1.75mmol) in dichloromethane (2mL) respectively and reacted at room temperature for 1 h. TLC detection, gas phase detection after the reaction is finished, and the yield is 78%. The equivalent of iodobenzene diacetate was increased compared to example 17, and the other conditions were unchanged.
EXAMPLE 20 TEMPO (14mg,0.09mmol) and iodobenzene diacetate (0.84g,2.6mmol) were added to a solution of (Z) -4-hepten-1-ol (0.2g,1.75mmol) in dichloromethane (2mL) respectively and reacted at room temperature for 2 h. TLC detection, gas phase detection after the reaction is finished, and the yield is 73%. The equivalent of TEMPO was reduced compared to example 17, with the other conditions being unchanged.
EXAMPLE 21 TEMPO (54.7mg,0.35mmol) and iodobenzene diacetate (0.84g,2.6mmol) were added to a solution of (Z) -4-hepten-1-ol (0.2g,1.75mmol) in dichloromethane (2mL) respectively and reacted at room temperature for 1 h. TLC detection, gas phase detection after the reaction is finished, and the yield is 78%. The equivalent of TEMPO was increased compared to example 17, with the other conditions being unchanged.
Step 6 preparation of (2E,6Z) -non-2, 6-dienal (8)
Example 22: to a solution of formylmethylenetriphenylphosphine (0.6g,1.96mmol) in 1, 4-dioxane (4mL) was added dropwise compound 7(0.2g,1.78mmol) at 0 deg.C, the reaction was carried out at room temperature for 16h, the solvent was recovered, and the product was purified by column chromatography to give (2E,6Z) -non-2, 6-dienal 8(94mg, 38%.1H NMR(400MHz,CDCl3):δ9.50(d,J＝7.84Hz,1H),6.82-6.89(m,1H),6.13(q,J＝7.88Hz,1H),5.42-5.47(m,1H),5.28-5.34(m,1H),2.40(q,J＝7.00Hz,2H),2.26(q,J＝7.16Hz,2H),2.01-2.08(m,2H),0.97(t,J＝7.52Hz,3H)；13C NMR(100MHz,CDCl3):δ＝194.0,158.1,133.3,133.2,126.7,32.7,25.4,20.6,14.2.
Example 23: compound 7(22.4mg,0.2mmol) was added dropwise to a solution of formylmethylenetriphenylphosphine (70mg,0.22mmol) in chloroform (0.5mL) at 0 deg.C, reacted at room temperature for 16h, the solvent was recovered, and purified by column chromatography to give (2E,6Z) -nonane-2, 6-dienal 8(7.2mg, 26%). The solvent was changed to chloroform, and the other conditions were not changed, as compared with example 22. Of the product1HNMR and13c NMR completely agreed with example 22.
Example 24: compound 7(22.4mg,0.2mmol) was added dropwise to a solution of formylmethylenetriphenylphosphine (70mg,0.22mmol) in dichloromethane (0.5mL) at 0 deg.C, reacted at room temperature for 16h, the solvent was recovered, and purified by column chromatography to give (2E,6Z) -nonane-2, 6-dienal 8(3.5mg, 13%). Compared to example 22, the solvent was changed to dichloromethane, and the other conditions were unchanged. Of the product1H NMR and13c NMR was in full agreement with example 20.
Example 25: to a solution of formylmethylenetriphenylphosphine (70mg,0.22mmol) in 1, 2-dichloroethane (0.5mL) was added dropwise compound 7(22.4mg,0.2mmol) at 0 deg.C, the reaction was carried out at room temperature for 16h, the solvent was recovered, and the product was purified by column chromatography to give (2E,6Z) -non-2, 6-dienal 8(5.4mg, 20%). Compared with example 22, the solvent was changed to 1, 2-dichloroethane, and other conditions were not changed. Of the product1H NMR and13c NMR completely agreed with example 22.
Example 26: to a solution of formylmethylenetriphenylphosphine (70mg,0.22mmol) in tetrahydrofuran (0.5mL) at 0 deg.C was added dropwise compound 7(22.4mg,0.2mmol), reacted at room temperature for 16h, the solvent was recovered, and purified by column chromatography to give (2E,6Z) -non-2, 6-dienal 8(7.6mg, 28%). The solvent was changed to tetrahydrofuran compared to example 22, and the other conditions were unchanged. Of the product1H NMR and13c NMR completely agreed with example 22.
Example 27: compound 7(22.4mg,0.2mmol) was added dropwise to a solution of formylmethylenetriphenylphosphine (70mg,0.22mmol) in acetonitrile (0.5mL) at 0 deg.C, reacted at room temperature for 16h, the solvent was recovered, and purified by column chromatography to give (2E,6Z) -nonane-2, 6-dienal 8(7.5mg, 27%). The solvent was changed to acetonitrile compared to example 22, and other conditions were unchanged. Of the product1HNMR and13c NMR completely agreed with example 22.
Example 28: compound 7(22.4mg,0.2mmol) was added dropwise to a solution of formylmethylenetriphenylphosphine (61mg,0.2mmol) in acetonitrile (0.5mL) at 0 deg.C, reacted at room temperature for 16h, the solvent was recovered, and purified by column chromatography to give (2E,6Z) -nonane-2, 6-dienal 8(7.5mg, 27%). Compared with the embodiment 22, the equivalent of the formyl methylene triphenylphosphine is reduced, and other conditions are not changed. Of the product1H NMR and13c NMR completely agreed with example 22.
And 7: (E) preparation of (1) -cis-6,7-epoxy-2-nonenal
Example 29: to a solution of compound 8(50mg,0.36mmol) in dichloromethane (2mL) was added m-chloroperoxybenzoic acid (80.2mg,0.39mmol, 85% purity) portionwise at 0 deg.C for 10min before moving to room temperature for 15 h. After quenching by addition of 5mL of a saturated sodium carbonate solution containing a small amount of sodium thiosulfate and separation of layers, the organic phase was collected, dried over anhydrous sodium sulfate and purified by column chromatography to give colorless liquid 1(36mg, 65%).1H NMR(400MHz,CDCl3):δ9.53(d,J＝7.80Hz,1H),6.88-6.95(m,1H),6.17(q,J＝7.84Hz,1H),2.91-2.98(m,2H),2.51-2.59(m,2H),1.78-1.83(m,1H),1.66-1.73(m,1H),1.50-1.61(m,2H),1.06(t,J＝7.52Hz,3H)；13C NMR(100MHz,CDCl3):δ193.9,157.1,133.4,58.4,56.3,29.9,26.2,21.1,10.6.
Example 30: to a solution of compound 8(50mg,0.36mmol) in dichloromethane (2mL) was added m-chloroperoxybenzoic acid (73mg,0.36mmol, 85% purity) portionwise at 0 deg.C, after 10min was allowed to cool to room temperature and reacted for 15 h. After quenching by addition of 5mL of a saturated sodium carbonate solution containing a small amount of sodium thiosulfate and separation of layers, the organic phase was collected, dried over anhydrous sodium sulfate and purified by column chromatography to give colorless liquid 1(30mg, 54%). The equivalent of m-chloroperoxybenzoic acid was reduced as compared with example 29, and the other conditions were not changed. Of the product1H NMR and13c NMR was in full agreement with example 29.

Claims (8)

1. The method for synthesizing the aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of the taurus communis is characterized by comprising the following steps: the specific synthesis steps are as follows:
(1) under the action of acid, 1, 4-butanediol and 3, 4-dihydro-2H-pyran react in a mixed solvent of tetrahydrofuran and dichloromethane to generate 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol;
the acid is pyridinium p-toluenesulfonate or p-toluenesulfonic acid monohydrate;
(2) oxidizing the 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol obtained in the step (1) with TEMPO and iodobenzene diacetate in dichloromethane to generate 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde;
(3) in a low-temperature nitrogen atmosphere, generating (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran from the 4- ((tetrahydro-2H-pyran-2-yl) oxy) butyraldehyde obtained in the step (2) and n-propyltriphenylphosphonium bromide salt and alkali in a tetrahydrofuran solution;
the low temperature is-100-50 ℃, and the alkali is potassium tert-butoxide, LHMDS or KHMDS;
(4) reacting the (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran obtained in the step (3) with the action of an acid to generate (Z) -4-hepten-1-ol;
the acid is 10% of HCl, pyridinium p-toluenesulfonate or p-toluenesulfonic acid monohydrate in percentage by mass;
(5) oxidizing the (Z) -4-hepten-1-ol obtained in the step (4) with TEMPO and iodobenzene diacetate in dichloromethane to generate (Z) -4-heptenal;
(6) reacting the (Z) -4-heptenal obtained in the step (5) with formyl methylene triphenylphosphine in an organic solvent to obtain (2E,6Z) -non-2, 6-dienal;
(7) epoxidizing the (2E,6Z) -nona-2, 6-dienal obtained in step (6) with m-chloroperoxybenzoic acid in dichloromethane to produce (E) -cis-6, 7-epoxy-2-nonenal.
2. The method for synthesizing avid aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of the pink-neck longicorn as claimed in claim 1, wherein the volume ratio of tetrahydrofuran to dichloromethane in the step (1) is 1: 10; wherein the molar ratio of the 3, 4-dihydro-2H-pyran to the 1, 4-butanediol is 1: 1-1.5.
3. The method for synthesizing avid aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal according to claim 1, wherein in the step (2), the molar ratio of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol to TEMPO is 1: 0.05-0.2; the molar ratio of 4- ((tetrahydro-2H-pyran-2-yl) oxy) butan-1-ol to iodobenzene diacetate is 1: 1-2.
4. The method for synthesizing avidinir mahogany gathering pheromone (E) -cis-6,7-epoxy-2-nonenal according to claim 1, wherein the solvent in the step (3) is anhydrous tetrahydrofuran.
5. The method for synthesizing avid aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of claim 1, wherein the molar ratio of the acid to the (Z) -2- (hept-4-en-1-yloxy) tetrahydro-2H-pyran in the step (4) is 1:10, and the solvent is methanol or ethanol.
6. The method for synthesizing avid aggregation pheromone (E) -cis-6,7-epoxy-2-nonenal of claim 1, wherein in the step (5), the molar ratio of (Z) -4-hepten-1-ol to TEMPO is 1: 0.05-0.2; the molar ratio of the (Z) -4-hepten-1-ol (6) to the iodobenzene diacetate is 1: 1-2.
7. The method for synthesizing aviptamin (E) -cis-6,7-epoxy-2-nonenal of Tanaemon rubrum according to claim 1, wherein the solvent in step (6) is chloroform, dichloromethane, 1, 2-dichloroethane, tetrahydrofuran, acetonitrile, 1, 4-dioxane, and the molar ratio of (Z) -4-heptenal to formylmethylenetriphenylphosphine is 1: 1-3.
8. The method for synthesizing avidinal (E) -cis-6,7-epoxy-2-nonenal of Taohorma persicae Hemsl according to claim 1, wherein the molar ratio of (2E,6Z) -non-2, 6-dienal to m-chloroperoxybenzoic acid in step (7) is 1: 1-2.
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