JP4311331B2 - Process for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde - Google Patents

Description

  The present invention relates to a process for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde useful as a fragrance.

  As a method for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde, Patent Document 1, Patent Document 2, Patent Document 3 and Non-Patent Document 1 are based on hydroformylation of safrole or isosafrole. Although a production method is described, there is a safety problem in terms of using carbon monoxide, and the yield is not sufficient, about 30%. Another problem was the formation of isomers that were difficult to separate.

  Non-Patent Document 2 describes a production method by Heck reaction using 4-bromo-1,2-methylenedioxybenzene and β-methylallyl alcohol as raw materials. There wasn't.

  Patent Document 4 describes a production method by reduction of piperonylidenepropanal, but an alcohol in which the desired 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde is further reduced. Therefore, separation was difficult for purification. Piperonylidenepropanal used in the production method is produced from isosafrole by non-patent document 3 or patent document 5 by condensation of heliotropin and propanal, and by patent document 6 by Vilsmeier reaction. However, the former has a low selectivity and a low yield (yield of about 30 to 50%), and the latter has a problem that a large amount of phosphorus waste is produced as a by-product.

  A 3-substituted phenyl-2-methylpropionaldehyde compound having a structure similar to 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde is produced from a 1-acetoxy-3-substituted phenyl-propene compound As a method for this, Patent Document 7 describes a method for producing 3- (p-isobutylphenyl-2-methylpropionaldehyde) which is hydrolyzed in the presence of excess alcohol using sulfuric acid. Document 8 describes a method for producing a 3-substituted phenyl-2-methylpropionaldehyde compound that is hydrolyzed with an excess of potassium carbonate.

  However, in these methods, the yield is low, hydrolysis requires a high temperature and a long time, and harsh reaction conditions are likely to cause side reactions such as aldol reaction. In addition, the production method described in Patent Document 8 is not a practical production method because a large amount of base is required.

  In the hydrolysis, the product is exposed to an alkaline aqueous solution or an acidic aqueous solution, so that its stability becomes a problem. Stability of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde, the target product of the present invention, in an alkaline aqueous solution (Reference Example 1) and an acidic aqueous solution (Reference Example 2) As a result of the investigation, it was found that the decomposition proceeded considerably even at room temperature, and that the stability of the product was low under these hydrolysis conditions.

As a production method other than hydrolysis, Patent Document 9 discloses a 3-substituted phenyl- of formula (4) in which a 1-acetoxy-3-substituted phenyl-propene compound of formula (3) is subjected to alcoholysis in the presence of a base. A process for the preparation of 2-methylpropionaldehyde compounds is described. However, since alkali is used, the stability of the product to alkali must be taken into account, as in the above-described hydrolysis.
In addition, there is no description of a method for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde.

(In the formula, R ¹ represents hydrogen, an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group, or a halogen atom, n represents an integer of 0 to 3, R ² represents hydrogen or a lower alkyl group, R ³ represents a lower alkyl group.)

JP-A-53-137963 JP-A-54-9271 German patent invention No. 2235466 Japanese Patent Publication No. 48-1380 U.S. Pat. No. 2,102,965 JP-A-10-120673 Japanese Patent Publication No.42-9135 Japanese Examined Patent Publication No. 45-23926 JP-A-53-2444 International Publication No. 04/054997 Pamphlet C1 Mol. Chem. 1985, p. 213 Journal of Organic Chemistry. 1976, 41, p. 1206 Am. Perfumer. 1930, p. 617

  An industrially suitable production method for obtaining 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde, which is useful as a fragrance, in good yield by a simple method.

As a result of intensive studies to solve the above-mentioned problems, the inventors have found that 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde, which is useful as a fragrance, is industrially simple and has a good yield. The present invention was completed by finding a suitable manufacturing method.
That is, the present invention is as follows.

  In the first invention, 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene represented by the formula (1) is reacted with an alcohol in the presence of a base. The present invention relates to a method for producing [1,3] dioxol-5-yl-2-methylpropionaldehyde.

  2nd invention is 3 of 1st invention whose usage-amount of a base is 0.001-0.05 times mole with respect to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene. -It relates to a process for producing benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde.

  According to a third invention, the amount of alcohol used is 3 to 14 times moles of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene. The present invention relates to a process for producing benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde.

  In a fourth invention, the alcohol is a group consisting of a linear lower aliphatic alcohol having 1 to 8 carbon atoms, a linear divalent lower aliphatic alcohol having 2 to 8 carbon atoms, and a mixture of these alcohols. The present invention relates to a process for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde according to any one of the first to third inventions.

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a simple and good industrial production method for 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde useful as a fragrance.

  According to the present invention, by reacting 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene represented by the formula (1) with an alcohol in the presence of a base, the formula (2) The 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde represented by this can be manufactured.

  According to the method described in Patent Document 10, 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene, which is a raw material compound of the present invention, is, for example, 3,3-diacetoxy-2-methylpropene and A product produced by reacting 1,2-methylenedioxybenzene in the presence of a catalyst such as a boron halide compound can be used.

Examples of the alcohol used in the present invention include linear lower aliphatic alcohols having 1 to 8 carbon atoms such as methanol, ethanol, propanol and butanol; linear alcohols having 2 to 8 carbon atoms such as ethylene glycol and propylene glycol. A divalent lower aliphatic alcohol or the like is used. Methanol, ethanol, propanol, ethylene glycol, and propylene glycol are preferably used, and methanol, ethanol, and ethylene glycol are more preferably used. These alcohols can also be used as a mixture.
The usage-amount of alcohol is 1 times mole-30 times mole with respect to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene, Preferably it is 3-14 times mole.
If the amount of the solvent used is lower than this range, the reaction is difficult to proceed and the yield is lowered. Further, if it is higher than this, the productivity is lowered.

  Examples of the base used in the present invention include alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, and calcium carbonate, and carbonates of alkaline earth metals; sodium hydrogen carbonate, potassium hydrogen carbonate, cesium hydrogen carbonate, etc. Alkali metal hydrides such as lithium hydride, sodium hydride and potassium hydride; metal alkoxides such as sodium methoxide, sodium ethoxide, potassium ethoxide and potassium tert-butoxide; lithium hydroxide, Alkali hydroxides or alkaline earth hydroxides such as sodium hydroxide, potassium hydroxide and calcium hydroxide can be mentioned, preferably alkali metal carbonates, alkali metal hydroxides and metal alkoxides, more preferably alkali metals. Carbonate, metal alkoxy De, is used. Of the alkali metal carbonates, potassium carbonate is most preferred, and among the metal alkoxides, sodium methoxide is most preferred. In addition, you may use these bases individually or in mixture of 2 or more types.

  The amount of the base used is preferably 0.001 to 1 mole, more preferably 0.001 to 0.05, based on 1 mole of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene. Double mole.

  The alkali metal or alkaline earth metal hydroxide or carbonate used in the present invention can also be used as an aqueous solution thereof, and the metal alkoxide can also be used as an alcohol solution. The concentration of these solutions is preferably 2 to 50 weight percent. This solution may be prepared separately.

  In the present invention, the reaction can be carried out in the absence of a solvent, but alcohol as a reaction raw material can also be used as a solvent. In addition to alcohol, a separate solvent may be used.

  The solvent used here is not particularly limited as long as it does not inhibit the reaction. For example, nitriles such as acetonitrile and propionitrile; ethers such as tetrahydrofuran and 1,4-dioxane; acetone, methyl ethyl ketone and the like Ketones; Halogenated aliphatic hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane; Aromatic hydrocarbons such as benzene, toluene, xylene; Anisole, veratrol, 1,2-methylenedioxybenzene, etc. Aromatic ethers; Halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene; Esters such as methyl acetate, ethyl acetate, and butyl acetate; N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone Amides such as dimethylsulfoxy Sulfoxides such as N; N, N′-dimethylimidazolidinone and the like, and preferably ethers, aromatic ethers, aromatic hydrocarbons, esters, more preferably ethers, aromatics Group ethers are used. These organic solvents may be used alone or in combination of two or more.

  The amount of the organic solvent used is appropriately adjusted depending on the uniformity and stirring properties of the reaction solution, but is preferably 0 with respect to 1 g of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde. .1 to 50 mL, more preferably 0.1 to 20 mL.

  The reaction temperature of this invention is 0-65 degreeC, Preferably it is 15-40 degreeC.

  Although reaction time changes with the usage-amount of a solvent and reaction temperature, it is 0.5 to 24 hours. As the reaction time becomes longer, decomposition of the product 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde proceeds, and the yield decreases. When the reaction time is short, the reaction is not completed.

  This reaction may be carried out in the air, but is usually carried out under an inert gas atmosphere such as argon gas or nitrogen gas, or under these gas streams. The reaction pressure used is usually atmospheric pressure.

  The synthesized 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde is neutralized after completion of the reaction, subjected to usual post-treatment such as extraction and concentration, and distilled as necessary. It can be appropriately purified by known means such as various types of chromatography.

Example 1.
Under an argon atmosphere, 2.34 g (10.0 mmol) of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene and 3.85 g (120.0 mmol) of methanol were added to a 10 mL three-necked flask. . To this was added 0.021 mg (0.15 mmol) of potassium carbonate, and the mixture was stirred at 19-22 ° C. for 1 hour.
After completion of the reaction, 0.027 g (0.45 mmol) of acetic acid was added to neutralize, and the resulting reaction solution was diluted with acetol with tolyl and water and quantified by high performance liquid chromatography. As a result, 3-benzo [1, 3] The yield of dioxol-5-yl-2-methylpropionaldehyde was 1.89 g (98.1% yield), and the conversion rate of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene was 100%.

Examples 2-3
Example 1 except that the amount of methanol used is 12 times the amount of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene and the amount of potassium carbonate is the amount shown in Table 1. The reaction was performed in the same manner. The results are shown in Table 1.

注）ＨＬＦ：３−ベンゾ［１，３］ジオキソール−５−イル−２−メチルプロピオンアルデヒド
ＡＭＤＢ：１−アセトキシ−３−（３，４−メチレンジオキシフェニル）プロペン

Note) HLF: 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde AMDB: 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene

Examples 4-14
Except that the amount of potassium carbonate used was 0.015 times mol and the amount of methanol used was 3 to 14 times mol with respect to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene, The reaction was performed in the same manner as in Example 1. The results are shown in Table 2.

注）ＨＬＦ：３−ベンゾ［１，３］ジオキソール−５−イル−２−メチルプロピオンアルデヒド
メタノールの使用量：１−アセトキシ−３−（３，４−メチレンジオキシフェニル）プロペン（ＡＭＤＢ）１モルに対するモル数

Note) HLF: 3-Benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde Methanol Amount used: 1 mol of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene (AMDB) Moles to

Examples 15-16
Example 1 except that the amount of methanol used relative to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene was 3 times the molar amount, and the amount of potassium carbonate used was the amount shown in Table 3. Reaction was performed. The results are shown in Table 3.

注）ＨＬＦ：３−ベンゾ［１，３］ジオキソール−５−イル−２−メチルプロピオンアルデヒド
ＡＭＤＢ：１−アセトキシ−３−（３，４−メチレンジオキシフェニル）プロペン

Note) HLF: 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde AMDB: 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene

Example 17
In a 100 mL four-necked flask, 23.4 g (100 mmol) of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene, 38.5 g (1200 mmol) of methanol and 1,2-methylenedioxybenzene 12. 21 g (100 mmol) was added. To this was added 0.07 g (0.5 mmol) of potassium carbonate, and the mixture was stirred at 23-24 ° C. for 1 hour.
After completion of the reaction, 0.09 g (1.5 mmol) of acetic acid was added for neutralization, and the resulting reaction solution was quantified by high performance liquid chromatography. As a result, 3-benzo [1,3] dioxol-5-yl-2 was obtained. -The yield of methylpropionaldehyde was 18.7 g (yield 97.0%), and the conversion of 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene was 100%.

Examples 18-20
The reaction was carried out in the same manner as in Example 1 except that the solvent was changed to ethanol, n-propanol, and ethylene glycol. The results are shown in Table 1.

Comparative Example 1
The reaction was performed in the same manner as in Example 1 except that the solvent was replaced with isopropanol. The results are shown in Table 1.

Reference example 1
In an argon atmosphere, 2.5 mL of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde and 2 mL of methanol were dissolved in a 10 mL eggplant-shaped flask and dissolved in this solution. 1.6 mL (2 mmol) of an aqueous sodium hydroxide solution having a concentration of 8 mol / L (liter) was added. Crystals precipitated when stirred overnight at room temperature. To this solution, 2.8 mL of methanol was added to make a uniform solution. At this time, the pH of the solution was 14. The pH was adjusted to 6.0 with 10.5 mL of hydrochloric acid having a concentration of 1 mol / L, and the reaction solution was quantified. As a result, the recovery rate of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde was 52.8%.

Reference example 2
Under an argon atmosphere, 1.95 g (10.0 mmol) of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde and 1.0 mL (10. 0 mmol) was added. When the mixture was stirred at room temperature for 5 hours, the viscosity of the reaction solution became high and stirring became difficult. When this solution was diluted with acetonitrile and quantified, the recovery of 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde was 67%.

Claims (4)

3-Benzo [1,3] dioxole represented by the formula (2) in which 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene represented by the formula (1) is reacted with an alcohol in the presence of a base A process for producing -5-yl-2-methylpropionaldehyde.

The 3-benzo [1,3 according to claim 1, wherein the amount of the base used is 0.001 to 0.05 moles compared to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene. Method for producing dioxol-5-yl-2-methylpropionaldehyde. The 3-benzo [1,3] according to claim 1 or 2, wherein the alcohol is used in an amount of 3 to 14 moles relative to 1-acetoxy-3- (3,4-methylenedioxyphenyl) propene. A process for producing dioxol-5-yl-2-methylpropionaldehyde. The alcohol is selected from the group consisting of linear lower aliphatic alcohols having 1 to 8 carbon atoms, linear divalent lower aliphatic alcohols having 2 to 8 carbon atoms, and mixtures of these alcohols. A process for producing 3-benzo [1,3] dioxol-5-yl-2-methylpropionaldehyde according to any one of -3.