Synthetic method of spodoptera frugiperda pheromone

Abstract

The invention discloses a synthesis method of spodoptera frugiperda pheromone, which comprises the following steps: by taking dibromoalkane and acetate as raw materials, carrying out single nucleophilic substitution reaction in an organic solvent to obtain omega-bromo-acetate, then reacting with triphenylphosphine to generate phosphine salt, and finally reacting with N-sulfonyl imine under the action of organic strong alkali to generate a target product. According to the present invention, the cheap and easily available commercially available reagents dibromoalkane and acetate are adopted as the starting raw materials, the reaction condition is mild, the reaction operation is simple and convenient, the reaction process is safe and controllable, the safe, effective and controllable synthesis route is provided for the industrial amplification production of the spodoptera frugiperda pheromone, and the practicality is strong.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical synthesis, and in particular to a method for synthesizing fall armyworm pheromone. Background Art

[0002] Fall armyworm, commonly known as fall armyworm, is an omnivorous pest and one of the world's top ten plant pests. The larvae of this moth like to eat corn, sugarcane, sorghum, potatoes and other plants. After being harmed, the yield will generally decrease by 20%-30%, and in severe cases, it will cause a total crop failure.

[0003] Fall armyworms are a major migratory pest for corn. If corn is damaged during the seedling stage, it can reduce the yield by 10%-25%. Severe damage to the field can lead to total crop failure. In fact, the reproduction capacity of fall armyworms far exceeds that of corn borers, the current number one pest of corn. Adult moths can fly 100 kilometers per night, and they have high reproduction rates and hatched larvae that are highly gluttonous and cause serious damage, which puts enormous pressure on prevention and control.

[0005] In order to prevent and control the fall armyworm, a comprehensive prevention and control strategy combining physical control, biological control, and chemical control has been formed in daily production. Among them, insect pheromones are compounds that regulate the attraction behavior of male and female insects. They are sensitive and specific, have a long range of action, and are highly attractive. Sex attractants are bionic high-tech products that simulate insect pheromones in nature and are released into the field through a releaser to kill pests of the opposite sex. This technology lures and kills pests without contacting plants and agricultural products. It has the advantages of high activity, low dosage, and no residual toxicity. It is one of the preferred methods for modern agricultural ecological pest control. I believe that with the vigorous development of green agriculture, the application prospects of insect pheromones will be broader.

[0006] The sex pheromone of fall armyworm consists of the following three components:

[0007]

[0008] The above three sex pheromone components of fall armyworm can be prepared into attractants in a certain proportion, added to a slow-release carrier to prepare a fall armyworm lure core, which can attract male adult fall armyworms by releasing specific volatile odors. This can not only monitor the occurrence period and amount of fall armyworms, but also achieve the purpose of trapping and killing, effectively reduce the population density of fall armyworms and alleviate their harm.

[0009] The existing synthesis routes of sex pheromones of fall armyworm are mostly as follows:

[0010]

[0011] In this synthetic route, ω-bromohydrin is used as a raw material to carry out functional group protection, alkyne nucleophilic substitution, defunctionalization, cis-hydrogenation and esterification reactions to obtain the target product cis-carbene acetate.

[0012] However, when implementing the technical solution created by the present invention, the inventors of the present application found that the raw materials used in the above-mentioned synthesis route are expensive, the production cost is high, and the cis hydrogenation reaction is highly dangerous and has poor safety, which is not conducive to industrial scale-up production, resulting in the sex pheromone of the fall armyworm failing to meet market demand. Summary of the invention

[0013] The present invention can solve the above-mentioned problems existing in the prior art by providing a method for synthesizing fall armyworm pheromone.

[0014] In order to solve the above technical problems, the present invention provides a method for synthesizing fall armyworm pheromone, and the synthesis route is as follows:

[0015]

[0016] Wherein, m is 5, 7 or 9;

[0017] R is at least one of methyl, trifluoromethyl, ethyl, propyl, butyl, phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.

[0018] In a preferred embodiment of the present invention,

[0019] In step (1), dibromoalkane and acetate are used as raw materials to carry out a single nucleophilic substitution reaction in an organic solvent, followed by filtration and purification to obtain ω-bromoacetate;

[0020] In step (2), the ω-bromoacetate prepared in step (1) and triphenylphosphine are heated under reflux in an organic solvent to react and generate a phosphine salt;

[0021] In step (3), the phosphonium salt prepared in step (2) and N-sulfonylimine are reacted under the action of a strong organic base to generate cis-carbenyl acetate, which is the fall armyworm pheromone.

[0022] In a preferred embodiment of the present invention, in step (1), the molar ratio of the dibromoalkane to the acetate is 1:1 to 1.2.

[0023] In a preferred embodiment of the present invention, in step (1), the temperature of the mononucleophilic substitution reaction is 60-80°C.

[0024] In a preferred embodiment of the present invention, the acetate is at least one of lithium acetate, sodium acetate, potassium acetate, ammonium acetate, aluminum acetate, copper acetate, iron acetate, strontium acetate, cesium acetate, calcium acetate, barium acetate, zinc acetate or manganese acetate.

[0025] In a preferred embodiment of the present invention, in step (2), the molar ratio of the ω-bromoacetate to triphenylphosphine is 1:1 to 1.2.

[0026] In a preferred embodiment of the present invention, in step (2), the reaction temperature for generating the phosphine salt is 80-100°C.

[0027] In a preferred embodiment of the present invention, in step (3), the molar ratio of the phosphonium salt, N-sulfonylimine and organic strong base is 1:1-1.2:1-1.2.

[0028] In a preferred embodiment of the present invention, in step (3), the reaction temperature for generating cis-carbene acetate is -60 to -50°C.

[0029] In a preferred embodiment of the present invention, the organic base is at least one of potassium tert-butoxide, sodium tert-butoxide, sodium cyclohexanol, sodium isopentanol, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, n-butyl lithium, tert-butyl lithium, phenyl lithium, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium tert-butoxide, sodium isooctanoate, sodium isodecanol, sodium 2-heptanol, 2-decanol lithium or 2-phenylethanol lithium.

[0030] The beneficial effects of the present invention are as follows: the method for synthesizing the fall armyworm pheromone of the present invention uses dibromoalkane and acetate, which are cheap and readily available commercial reagents, as starting materials, has mild reaction conditions, simple reaction operation, and a safe and controllable reaction process, thus providing a safe, effective, and controllable synthesis route for the industrialized scale-up production of the fall armyworm pheromone, and has strong practicality. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 This is the nuclear magnetic spectrum of cis-7-dodecene-1-acetate prepared in a preferred embodiment 1 of a method for synthesizing fall armyworm pheromone of the present invention. DETAILED DESCRIPTION

[0032] The preferred embodiments of the present invention are described in detail below in conjunction with the accompanying drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present invention.

[0033] The following is a detailed description of the preferred embodiments of the present invention so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present invention.

[0034] The present invention discloses a method for synthesizing fall armyworm pheromone, using commercially available reagents dibromoalkane and acetate as raw materials, which are cheap and easily available, and effectively reduce production costs. The specific synthesis steps are as follows:

[0035] Step (1): using dibromoalkane and acetate as raw materials, in a molar ratio of 1:1 to 1.2, in an organic solvent, a single nucleophilic substitution reaction is carried out at 60 to 80° C. After the reaction, ω-bromoacetate is obtained by extraction, washing, filtering and column chromatography;

[0036] Wherein, the acetate is at least one of lithium acetate, sodium acetate, potassium acetate, ammonium acetate, aluminum acetate, copper acetate, iron acetate, strontium acetate, cesium acetate, calcium acetate, barium acetate, zinc acetate or manganese acetate; preferably lithium acetate, sodium acetate, potassium acetate or zinc acetate.

[0037] The organic solvent is at least one of tetrahydrofuran, methyltetrahydrofuran, N,N-dimethylformamide, isopropanol, butanol, isopentanol, cyclohexanol, 2-heptanol, methyl cyclopentyl ether, methyl tert-butyl ether, hexamethylphosphoric triamide, N,N-diethylformamide, ethylene glycol dimethyl ether or dimethyl sulfoxide, preferably N,N-dimethylformamide, hexamethylphosphoric triamide, N,N-diethylformamide or dimethyl sulfoxide.

[0038] Step (2): heating the ω-bromoacetate prepared in step (1) and triphenylphosphine in an organic solvent at a molar ratio of 1:1 to 1.2 at 80 to 100° C. for reflux reaction, cooling, filtering, and drying to obtain a phosphonium salt;

[0039] In this step, the organic solvent is at least one of benzene, toluene, xylene, fluorobenzene, chlorobenzene, tetrahydrofuran, methyltetrahydrofuran, ethylene glycol dimethyl ether, 1,2-dichloroethane, ethylene glycol, ethanol, isopropanol or carbon tetrachloride, preferably toluene, xylene, tetrahydrofuran or 1,2-dichloroethane.

[0040] Step (3): add N-sulfonylimine and organic strong base to the reaction solution of phosphine salt in step (2), control the molar ratio of phosphine salt, N-sulfonylimine and organic strong base to be 1:1-1.2:1-1.2, cool to -60--50°C to react and generate cis-carbenyl acetate, which is the fall armyworm pheromone.

[0041] The organic base is at least one of potassium tert-butoxide, sodium tert-butoxide, sodium cyclohexanol, sodium isopentanol, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, n-butyl lithium, tert-butyl lithium, phenyl lithium, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium tert-butoxide, sodium isooctanoate, sodium isodecanol, sodium 2-heptanol, lithium 2-decanol or lithium 2-phenylethanol, preferably n-butyl lithium, lithium diisopropylamide, lithium hexamethyldisilazide.

[0042] In this step, the reaction solvent is at least one of toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, dimethyltetrahydrofuran, methyl tert-butyl ether, methyl cyclopentyl ether, diisopropyl ether or ethylene glycol dimethyl ether, preferably tetrahydrofuran, methyl cyclopentyl ether or ethylene glycol dimethyl ether.

[0043] The above reaction process is as follows:

[0044]

[0045] Wherein, m is 5, 7 or 9;

[0046] R is at least one of methyl, trifluoromethyl, ethyl, propyl, butyl, phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl, preferably methyl, phenyl or p-tert-butylphenyl.

[0047] The implementation process of the present invention is described in detail below through specific embodiments.

[0048] Example 1

[0049]

[0050] 12.9 g of 1,7-dibromoheptane, 4.9 g of sodium acetate and 100 ml of N,N-dimethylformamide were added to the reaction bottle, and the mixture was heated to 80°C for reaction. The reaction was detected to be complete by gas phase detection. The mixture was cooled and diluted with 250 ml of water. The mixture was extracted with ethyl acetate three times. The organic phases were combined and washed with saturated brine twice. The organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 15:1) to obtain 10.9 g of 7-bromohept-1-ol acetate with a yield of 92%.

[0051] 7.1 g of 7-bromoheptyl-1-ol acetate, 8.6 g of triphenylphosphine and 100 ml of toluene were added to the reaction flask, heated under reflux for 8 hours, cooled, filtered and dried to obtain 14.4 g of 7-acetoxyheptyltriphenylphosphonium bromide with a yield of 96%.

[0052] Under the protection of high-purity nitrogen, 10 g of 7-acetoxyheptyltriphenylphosphonium bromide and 200 ml of tetrahydrofuran were added to the reaction bottle, cooled to -60°C, 22 ml of n-butyl lithium-n-hexane solution (1.0M) was slowly injected, and stirred for 1 hour; 3.6 g of N-pentylene methanesulfonamide / 50 ml of tetrahydrofuran solution was slowly injected, and the reaction was continued at -60°C with stirring for 2 hours, and then the temperature was naturally raised to room temperature and the reaction was overnight; the reaction was quenched with ice water, concentrated to remove the organic solvent, extracted with ethyl acetate, the organic phases were combined, washed twice with saturated brine, the organic phases were dried with anhydrous sodium sulfate, filtered, the filtrate was concentrated, and the residue was purified by column chromatography (400 mesh silica gel, petroleum ether: ethyl acetate = 50:1) to obtain 4 g of cis-7-dodecene-1-acetate, with a yield of 89%; 1 HNMR (400MHz, CDCl3): δ5.36-5.34 (m, 2H), 4.05 (t, J=6.8Hz, 2H), 2.04 (s, 3H), 2.03-1.98 (m, 4H), 1.64-1.59 (m, 2H), 1.37-1.30 (m, 10H), 0.89 (t, J=4.0Hz, 3H); HRMS (ESI)calcdfor C 14 H 26 NaO2 + [M + Na + ]249.1830, found 249.1825.

[0053] Example 2

[0054]

[0055] 14.3 g of 1,9-dibromononane, 5.4 g of potassium acetate and 80 ml of hexamethylphosphoric triamide were added to the reaction bottle, and the reaction was heated to 60°C for reaction. The reaction was complete after gas phase detection. The mixture was cooled and diluted with 250 ml of water. The mixture was extracted with ethyl acetate three times. The organic phases were combined and washed with saturated brine twice. The organic phases were dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 15:1) to obtain 12.1 g of 9-bromononan-1-ol acetate with a yield of 91%.

[0056] 5.3 g of 9-bromononan-1-ol acetate, 5.8 g of triphenylphosphine and 100 ml of xylene were added to the reaction flask, heated to reflux for 6 hours, cooled, filtered and dried to obtain 9.7 g of 9-acetoxynonyltriphenylphosphonium bromide with a yield of 92%.

[0057] Add 5.3 g of 9-acetoxynonyltriphenylphosphonium bromide and 200 ml of tetrahydrofuran to the reaction flask, stir to dissolve, add 2.7 g of N-pentylenebenzenesulfonamide, stir for 30 minutes, and use high-purity nitrogen to replace 3 times for protection; cool to -50°C, slowly inject 6 ml of diisopropylamine lithium solution (2M), continue to stir at -50°C for 2 hours; then naturally warm to room temperature and react for 2 hours; add 10 ml of water to quench the reaction, concentrate to remove the solvent, add 100 ml of petroleum ether and stir for 30 minutes, filter, wash the filtrate with brine, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (400 mesh silica gel, petroleum ether: ethyl acetate = 50:1) to obtain 2.2 g of cis-9-tetradecene-1-acetate, with a yield of 88%; 1 H NMR (400MHz, CDCl3): 5.36-5.34 (m, 2H), 4.05 (t, J=6.8Hz, 2H), 2.04 (s, 3H), 2.02-1.99 (m, 4H), 1.63-1.59 (m, 2H), 1.34-1.30 (m, 14H), 0.90 (t, J=4.0Hz, 3H); HRMS (ESI)calcd for C 16 H 30 NaO2 + [M + Na + ]277.2143,found277.2140.

[0058] Example 3

[0059]

[0060] 15.7 g of 1,11-dibromodecane, 4 g of lithium acetate and 80 ml of dimethyl sulfoxide were added to the reaction bottle, and the mixture was heated to 80°C for reaction. The reaction was complete after gas phase detection. The mixture was cooled and diluted with 250 ml of water. The mixture was extracted with ethyl acetate three times. The organic phases were combined and washed with saturated brine twice. The organic phases were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 15:1) to obtain 13.9 g of 11-bromodecane-1-ol acetate with a yield of 95%.

[0061] Add 8.8 g of 11-bromondecene-1-ol acetate, 9.4 g of triphenylphosphine and 100 ml of xylene to the reaction flask, heat and reflux for 6 hours, cool, filter and dry to obtain 15.7 g of 9-acetoxynonyltriphenylphosphonium bromide with a yield of 94%.

[0062] Under high-purity nitrogen protection, 5.6 g of 9-acetoxynonyltriphenylphosphine bromide and 100 ml of tetrahydrofuran were added to the reaction bottle, cooled to -50°C, 8 ml of hexamethyldisilazide lithium tetrahydrofuran solution (1.5M) were slowly injected, and stirred for 1 hour; 2.5 g of N-pentylene p-toluenesulfonamide / 25 ml of tetrahydrofuran solution were slowly injected, and the reaction was continued at -50°C with stirring for 2 hours, and then the temperature was naturally raised to room temperature to react overnight; the reaction was quenched with ice water, concentrated to remove the organic solvent, extracted with ethyl acetate, the organic phases were combined, washed twice with saturated brine, the organic phases were dried with anhydrous sodium sulfate, filtered, the filtrate was concentrated, and the residue was purified by column chromatography (400 mesh silica gel, petroleum ether: ethyl acetate = 50:1) to obtain 2.4 g of cis-11-hexadecene-1-acetate, with a yield of 86%; 1 H NMR (400MHz, CDCl3): δ5.36-5.34 (m, 2H), 4.05 (t, J=6.8Hz, 2H), 2.04 (s, 3H), 2.02-1.9 8(m, 4H), 1.63-1.59(m, 2H), 1.34-1.26(m, 18H), 0.89(t, J=4.0Hz, 3H); HRMS(ESI)calcd for C 18 H 34 NaO2 + [M + Na + ]305.2457, found 305.2460.

[0063] Example 4

[0064]

[0065] The difference from Example 1 is that, under the protection of high-purity nitrogen, 2.5 g of 7-acetoxyheptyltriphenylphosphonium bromide and 50 ml of tetrahydrofuran are added to the reaction flask, cooled to -50°C, 6 ml of n-butyllithium-n-hexane solution (1.0M) are slowly injected, and stirred for 1 hour; 1.7 g of N-pentylene p-tert-butylbenzenesulfonamide / 25 ml of tetrahydrofuran solution are injected, and the reaction is continued at -50°C with stirring for 5 hours, and stirred at room temperature overnight; 10 ml of water is added dropwise to quench the reaction, the solvent is concentrated to remove, 50 ml of petroleum ether is added, stirred for 30 minutes, filtered, dried over sodium sulfate, concentrated, and the residue is purified by column chromatography (400 mesh silica gel, petroleum ether: ethyl acetate = 150:1) to obtain 0.96 g of cis-7-dodecene-1-acetate, with a yield of 85%, and the product 1 The HNMR and HRMS detection data are completely consistent with those in Example 1.

[0066] The invention discloses a method for synthesizing fall armyworm pheromone, which uses commercially available reagents as raw materials, has a simple and convenient synthesis process, mild and controllable synthesis conditions, and high safety. On the one hand, it overcomes the many defects of the existing method for synthesizing fall armyworm sex pheromone cis-carbenyl acetate, such as harsh reaction conditions, expensive reagents, complicated operation, and low yield; on the other hand, it eliminates reactions with high difficulty and poor controllability, such as cis hydrogenation. The new synthesis method of the invention realizes the mass production of cis-carbenyl acetate, thereby meeting the market demand for fall armyworm sex pheromone, and is of great significance for controlling the reproduction and number of fall armyworm, protecting and increasing grain production, and promoting the development of green agriculture.

[0067] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing pheromone of fall armyworm, characterized in that: The synthetic route is as follows: Wherein, m is 5, 7 or 9; R is at least one of methyl, trifluoromethyl, ethyl, propyl, butyl, phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.

2. The method for synthesizing fall armyworm pheromone according to claim 1, characterized in that: In step (1), dibromoalkane and acetate are used as raw materials to carry out a single nucleophilic substitution reaction in an organic solvent, followed by filtration and purification to obtain ω-bromoacetate; In step (2), the ω-bromoacetate prepared in step (1) and triphenylphosphine are heated under reflux in an organic solvent to react and generate a phosphine salt; In step (3), the phosphonium salt prepared in step (2) and N-sulfonylimine are reacted under the action of a strong organic base to generate cis-carbenyl acetate, which is the fall armyworm pheromone.

3. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (1), the molar ratio of the dibromoalkane to the acetate is 1:1 to 1.

2.

4. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (1), the temperature of the single nucleophilic substitution reaction is 60-80°C.

5. The method for synthesizing fall armyworm pheromone according to claim 2 or 3, characterized in that: The acetate is at least one of lithium acetate, sodium acetate, potassium acetate, ammonium acetate, aluminum acetate, copper acetate, iron acetate, strontium acetate, cesium acetate, calcium acetate, barium acetate, zinc acetate or manganese acetate.

6. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (2), the molar ratio of the ω-bromoacetate to triphenylphosphine is 1:1 to 1.

2.

7. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (2), the reaction temperature for generating the phosphine salt is 80-100°C.

8. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (3), the molar ratio of the phosphonium salt, N-sulfonyl imide and the organic strong base is 1:1-1.2:1-1.

2.

9. The method for synthesizing fall armyworm pheromone according to claim 2, characterized in that: In step (3), the reaction temperature for generating cis-carbene acetate is -60 to -50°C.

10. The method for synthesizing fall armyworm pheromone according to claim 2 or 8, characterized in that: The organic base is at least one of potassium tert-butoxide, sodium tert-butoxide, sodium cyclohexanol, sodium isopentanol, lithium diisopropylamide, sodium bis(trimethylsilyl)amide, n-butyl lithium, tert-butyl lithium, phenyl lithium, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide, lithium tert-butoxide, sodium isooctanoate, sodium isodecanol, sodium 2-heptanol, lithium 2-decanol or lithium 2-phenylethanol.

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