JPS6277344A - Production of benzaldehyde - Google Patents

Abstract

PURPOSE:In formulating a benzene derivative by the use of both a formamide compound and a condensation agent, to obtain a benzaldehyde useful as an intermediate for drugs, agricultural chemicals, etc., by adding a salt to the reaction system to suppress a decomposition reaction. CONSTITUTION:In producing a benzaldehyde by Vilsmeier reaction in which a benzene derivative is formulated by the use of both a formamide compound such as dimethylformamide, N-methylformanilide, etc., and a condensation agent such as POCl3, SOCl2, COCl2, etc., usually 0.5-100mol, preferably 0.8-20mol based on a mol raw material of a salt of a metal preferably of group IA or IIA, especially halide, such as chloride, bromide or fluoride of Li, Na or K, MgCl2, CaCl2, etc., is added to the reaction system and decomposition of a complex as an intermediate reaction product is suppressed, to improve yield of the aimed compound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing benzaldehydes, which are compounds useful as intermediates in the production of pharmaceuticals, agricultural chemicals, and the like.

[Conventional technology]

The method for introducing formyl groups into benzene derivatives is as follows:
Conventionally, formamide compounds such as dimethylformamide and N-methylformanilide and POClj, So
C'12. A condensing agent like Cock□? The so-called Vi'lsmeier Vi
The IBmeier reaction is widely used as a means of synthesizing organic compounds because of its easy operation and mild reaction conditions.

[Problem that the invention seeks to solve]

However, this method also has the drawback that the reaction yield is not sufficiently high.

The reason for the low yield is the thermal decomposition of the intermediate complex. If an attempt is made to suppress the decomposition by lowering the temperature, the reaction rate will decrease, and if the reaction is carried out for a long time to increase the reaction yield at a low temperature, a decomposition reaction will occur.

[Means for solving problems]

The present inventors investigated the Vilsmeiθr reaction and found that the presence of a salt in the reaction system suppresses the decomposition reaction and improves the yield.

That is, the gist of the present invention resides in a method for producing benzaldehydes, which comprises formylating in the presence of a salt when producing benzaldehydes by diformylating a benzene derivative with a formamide compound and a condensing agent.

The present invention will be explained in detail below.

The benzene derivative used in the present invention means substituted benzenes.

As a substituent, an alkyl group or an alkoxy group is used.

Examples include a monoalkyl- or dialkyl-substituted amino group and a hydroxy group, and two or more types of these substituents may be substituted.

Furthermore, the benzene derivative used in the present invention is Vilsr
It is necessary that the substituted benzene is active in the neiθr reaction.

Substituted benzenes active in Vilemeiθr reaction are:
Vi'lθmθier refers to substituted benzenes with which the complex can react electrophilically.

Substituted Hensens are anisole compounds. It is classified into phenolic compounds, aniline compounds and alkylbenzene compounds.

An example of anisole compound is anisole.

Comethylanisole, 3-methylanisole.

Examples include s,r-dimethylanisole, co,3-dimethylanisole, /, 2-dimethoxybenzene, /, 3-dimethoxybenzene, 2,3-methylenedioxyanisole, and the like.

An example of a phenolic compound is phenol.

3-dihydroxybenzene 1.2 is 1-dimethylphenyl, 1
/-le, ,2. ．． Examples include 7-methylenedioxyphenol.

Examples of aniline compounds include N-methylaniline, N
, N-,) methylaniline, 3-methyl-N, N-symylaniline, N,N-diethylaniline, and the like.

Examples of alkylbenzene compounds include toluene, xylene, ethylbenzene, flobylbenzene, butylbenzene, and the like.

Further, an example of the formamide compound used in the present invention is N,N-dimethylformamide.

N, N-diethylformamide, N-methylpolanilide, formanilide, N-formylsulfoline, N
-Phenylformani! J)”IE can be mentioned.

The amount of formamide compound to be used is usually 0.00% per mole of benzene derivative. ．． 2 to 10 times the mole.

Preferably, it is 0.5 to 3 times the mole.

In addition, the condensing agent used in the present invention includes poet.

GOCI2.8001□ is used. The amount of condensing agent used is usually 0.2 to 1 per 7 moles of benzene derivative.
It is 0 times the mole, preferably 0.5 to 3 times the mole.

The salts used in the present invention are preferably salts of metals in groups A and IA, particularly halides of metals in groups IA and uA.

Specifically, LiC1, LiBr, LiF.

NaCl, NaBr, NaF, KCI, K
Br, KF, MgCl2. There are CaC1°, etc. The amount of salt used is usually o,
The amount used is s to ioo times the mole, preferably 0, g -:10 times the mole. The reaction temperature is usually 20 to 7.50°C,
Preferably, go~/ko0°C.

In the reaction, a complex of a formamide compound and a condensing agent may be prepared in advance and then the formylation may be carried out.
Any method of simultaneously performing complex formation and formylation may be used.

After the reaction is completed, the treatment is carried out in the same manner as the usual Vi1-day Meier reaction.

(Examples) Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to the following Examples unless the gist thereof is exceeded.

Example/ In a nitrogen stream, phosphorus oxytrichloride,! 2g
(/b, a mmol) was added dropwise to prepare a Willsmeyer complex in advance. Next is KFO, 9! g(/
iQ mmol) was added to the Willsmeyer complex at room temperature, and the mixture was stirred for 70 minutes. 7th,
Co, 3-methylenedioxyanisole/, OE (b,
s b mol) was added thereto, and the mixture was heated and stirred in an oil bath/gO°C for 2 hours. The reaction solution turned reddish brown and viscous. After the reaction solution was cooled to room temperature, it was poured into 30 nt of ice water, and a dilute Na0)] solution was added to complete the hydrolysis (pH ~//), followed by extraction with ethyl acetate. The extracted coffin was resistant with 1 #J sulfuric acid, then washed with water, and then analyzed by heavy-speed liquid chromatography. The analysis results are shown in Table-/.

EXAMPLE An experiment was carried out in exactly the same manner as in Example 1, except that ECO, 7J, l/iF mmol) was used instead of K2O as the salt.

The analysis results are shown in Table-/.

Example 3 As a salt, Na013. instead of K2O. εdaS(/A,
An experiment was conducted in exactly the same manner as in Example 1, except that tI mmol) was used.

The analysis results are shown in Table-/.

Comparative Example/Real measurements were carried out in exactly the same manner as in Example/, except that nothing was used as the salt in place of K2O.

Minute Ur results are shown in light-/.

(Effects of the Invention) According to the method of the present invention, benzaldehydes useful as intermediates for producing pharmaceuticals, agricultural chemicals, etc. can be produced in high yield.

Sender: Mitsubishi Chemical Industries, Ltd. Representative Patent Attorney Naga Kagawa - Others/names

Claims (1)

[Claims] (1) A method for producing benzaldehydes, which comprises formylating a benzene derivative with a formamide compound and a condensing agent to produce benzaldehydes in the presence of a salt.