CN-121990894-A - Synthesis method of piperonyl

Abstract

The invention discloses a synthesis method of piperonyl, which relates to the technical fields of essence and perfume and chemical industry, and comprises the steps of taking acrylic ester as a raw material, carrying out Michael addition reaction with isobutene under the action of Lewis acid to obtain 5-methyl-5-hexenoic acid ethyl ester, carrying out nucleophilic substitution reaction on the 5-methyl-5-hexenoic acid ethyl ester and bromoisopropyl under the action of an alkaline catalyst to obtain 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester, carrying out self-Friedel-crafts acylation reaction on the 5-methyl-2-isopropyl-5-chlorocyclohexanone under the action of Lewis acid to obtain 5-methyl-2-isopropyl-5-chlorocyclohexanone, and carrying out elimination reaction on the 5-methyl-2-isopropyl-5-chlorocyclohexanone under the action of alkali to obtain piperonyl. The synthetic route of the invention uses the conventional chemical reagent as the raw material, has mild reaction conditions, greatly reduces the emission of three wastes, is more environment-friendly, and is suitable for continuous industrial production.

Inventors

• ZOU YUANLIN
• HUANG XIANGWEI
• WANG CONG
• Fu Hongde
• YE LEI
• YANG ZHI
• CHEN LIANGXIAN
• ZHANG MIN

Assignees

• 四川博越汇生物科技有限公司

Dates

Publication Date

20260508

Application Date

20260123

Claims (10)

1. 1. The synthesis method of piperonyl comprises the following steps: step one, acrylic ester is used as a raw material, and Michael addition reaction is carried out on the acrylic ester and isobutene under the action of Lewis acid to obtain 5-methyl-5-hexenoic acid ethyl ester; Step two, nucleophilic substitution reaction is carried out on the 5-methyl-5-hexenoic acid ethyl ester and bromoisopropyl under the action of an alkaline catalyst, so as to obtain the 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester; Step three, carrying out self-friedel-crafts acylation reaction on the 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester under the action of Lewis acid to obtain 5-methyl-2-isopropyl-5-chlorocyclohexanone; And step four, carrying out elimination reaction on the 5-methyl-2-isopropyl-5-chlorocyclohexanone under the action of alkali to obtain the product piperonyl.
2. 2. The method for synthesizing piperonyl alcohol according to claim 1, wherein in the first step, the Lewis acid is one or more of aluminum trichloride, boron trifluoride tetrahydrofuran solution, ferric trichloride and zinc chloride.
3. 3. The method of synthesizing piperonyl alcohol according to claim 1, wherein in step one, the lewis acid used is aluminum trichloride, and the molar equivalent of aluminum trichloride is 15% -65% of that of acrylic ester.
4. 4. The method for synthesizing piperonyl alcohol according to claim 1, wherein in the second step, the basic catalyst is one or more of methanol solution of sodium methoxide (w/w), ethanol solution of sodium ethoxide (w/w), tetrahydrofuran solution of potassium tert-butoxide (w/w), tetrahydrofuran solution of lithium diisopropylamide (w/w), and tetrahydrofuran solution of lithium hexamethyldisilazide (w/w).
5. 5. The method for synthesizing piperonyl ketone according to claim 1, wherein in the second step, the alkaline catalyst is 20% (w/w) of lithium hexamethyldisilazide in tetrahydrofuran, and the weight of the alkaline catalyst is 50% -120% of ethyl 5-methyl-5-hexenoate.
6. 6. The method for synthesizing piperonyl alcohol according to claim 1, wherein in the third step, the solvent is one or more of toluene, xylene, tetrahydrofuran, n-heptane, n-hexane, nitroethane and nitropropane.
7. 7. The method for synthesizing piperonyl alcohol according to claim 1, wherein in the third step, the Lewis acid is one or more of aluminum trichloride, boron trifluoride tetrahydrofuran solution, ferric trichloride and zinc chloride.
8. 8. The method for synthesizing piperonyl ketone according to claim 1, wherein in the third step, the Lewis acid is aluminum trichloride, and the weight of aluminum trichloride is 20% -80% of that of ethyl 5-methyl-2-isopropyl-5-hexenoate.
9. 9. The method for synthesizing piperonyl alcohol according to claim 1, wherein in the fourth step, the alkali is one or more of sodium hydroxide, potassium hydroxide, sodium ethoxide and sodium methoxide.
10. 10. The method for synthesizing piperonyl ketone according to claim 1, wherein in the fourth step, the alkali is sodium hydroxide, and the weight of sodium hydroxide is 50% -120% of that of 5-methyl-2-isopropyl-5-chlorocyclohexanone.

Description

Synthesis method of piperonyl Technical Field The invention relates to the technical fields of essence and spice and chemical industry, in particular to a synthesis method of piperonyl. Background The piperonyl chemical name is 6-isopropyl-3-methyl-2-cyclohexene-1-one, is a naturally occurring cyclic menthone, is one of characteristic components of the peppermint oil, exists in Asian peppermint and peppermint, and has camphor-like smell and spicy peppermint flavor. The piperonyl has wide application in daily chemicals and foods, so the piperonyl has great application value, and the synthesis method thereof is always focused. Khimiya, prirodnykh et al report a process for the synthesis of piperonyl butoxide using thymol methyl ether as the starting material, followed by a Berry reduction (metallic lithium and ethylenediamine-isopropanol action) and an acidic hydrolysis to give piperonyl butoxide with a selectivity of 63.5%. The scheme uses high-activity metal lithium for birch reduction, so that the method has no industrial practical value. CHEMISCHE BERICHTE 82,112-116,1949 reports that the product is obtained by Michael addition reaction, intramolecular cyclization and hydrolytic decarboxylation of ethyl alpha-isopropyl acetoacetate and methyl vinyl ketone. The disadvantage of this process is that the starting materials are synthesized by themselves, that the methyl vinyl ketone market is not on the market, that they are synthesized by themselves and that they are toxic. Tamotsu Fujisawa et al report that 2-methyl-2-pentenyl bromide is used as a Grignard reagent to react with methylcyclobutyrolactone to obtain citronellic acid, citronellic acid reacts with thionyl chloride to obtain citronellyl chloride, boron trifluoride diethyl etherate is used as a catalyst at room temperature, dichloromethane is used as a solvent, and then dehydrochlorination is carried out under the action of potassium carbonate to obtain the product. The method has the defects that the reaction has higher requirements on experimental conditions, and the Grignard reagent can generate a large amount of magnesium salt wastewater. BASF reported in US3962341 that piperonyl is produced by reacting 3-methyl-2-butenal as a starting material and pentane as a solvent at high temperature with formic acid. Takasago reports a metal catalyst for the site-selective hydrogenation of piperonyl at high pressure to yield piperonyl. CN103755539A reports that piperonyl is synthesized by a 4-step method, methyl isobutyl ketone is firstly used as a raw material, the raw material reacts with formaldehyde under the action of hydrogen chloride to obtain an intermediate 3-isopropyl-3-butene-2-one, then the 3-isopropyl-3-butene-2-one is subjected to Michael addition under the catalysis of alkali to obtain an intermediate methyl 2-acetyl-4-isopropyl-5-oxo-hexanoate, the methyl 2-acetyl-4-isopropyl-5-oxo-hexanoate is subjected to intramolecular condensation under the alkaline condition to obtain carboxylic ester of piperonyl, and the carboxylic ester of piperonyl is hydrolyzed and decarboxylated under the alkaline condition to obtain piperonyl. The method has the defects of high corrosiveness of hydrogen chloride gas in the first step, high requirements on production equipment, high acid wastewater generated by excessive HCl gas, and low selectivity of the intramolecular condensation reaction in the third step, thus lower total yield. In summary, the prior art related to the synthesis method of piperonyl has the following problems that the starting materials are not easy to obtain, or expensive metal catalysts which cannot be recovered are used, or toxic raw materials and intermediates are used, so that the cost is quite high, the environmental protection and safety problems are outstanding, and the industrial production practicability is not strong. Disclosure of Invention In order to solve the defects in the prior art, the invention provides the synthesis method of piperonyl, which has the advantages of reduced cost, mild reaction conditions, environmental friendliness and suitability for industrial production. In order to achieve the object of the invention, the following scheme is adopted: A synthesis method of piperonyl comprises the following steps: step one, acrylic ester is used as a raw material, and Michael addition reaction is carried out on the acrylic ester and isobutene under the action of Lewis acid to obtain 5-methyl-5-hexenoic acid ethyl ester; Step two, nucleophilic substitution reaction is carried out on the 5-methyl-5-hexenoic acid ethyl ester and bromoisopropyl under the action of an alkaline catalyst, so as to obtain the 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester; Step three, carrying out self-friedel-crafts acylation reaction on the 5-methyl-2-isopropyl-5-hexenoic acid ethyl ester under the action of Lewis acid to obtain 5-methyl-2-isopropyl-5-chlorocyclohexanone; And step four, carrying out elimination reaction on the 5-methyl-2-isop