JP2586949B2 - Method for producing p- or m-hydroxybenzaldehyde - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION a) Object of the Invention (Industrial Application Field) The present invention relates to p- or m-
The present invention relates to a method for producing hydroxybenzaldehyde.

(Prior Art) Several methods for producing hydroxybenzaldehyde are known. For example, the diazotization of p-aminobenzaldehyde followed by hydrolysis affords p-hydroxybenzaldehyde [Reckille.
De Travoc Simic de Paypa, Vol. 54, p. 97 (1935)
)], P-hydroxybenzaldehyde can be obtained by condensation of phenol and formaldehyde in an alkaline solution and post-treatment with sodium salt of 3-nitrobenzolsulfonic acid (German Patent 580981), p-hydroxybenzonitrile Hydrogenation of p-hydroxybenzaldehyde [Herpetica Simica Acta Vol. 19, p. 588 (1936)],
Chlorination of p-tolyl chloroformate and alkaline saponification of the product to give p-hydroxybenzaldehyde (DE-A 19 25 195), treatment of phenol with glyoxylic acid and of the product with mercuric chloride solution Finishing to give p-hydroxybenzaldehyde (German Patent 62
1567), heating p-methoxybenzaldehyde to 200-220 ° C. in the presence of pyridinium hydrochloride to give p-methoxybenzaldehyde.
That hydroxybenzaldehyde can be obtained [Berichte del Deutschen Cheng Hemischen Geserschaft Vol. 74 (7) p. 1219 (1941)], p-hydroxybenzaldehyde by the reaction of phenol with trichloroacetic acid and the alkaline hydrolysis of the product. [Journal of Chemical Society, p. 496 (1
935)], the reaction of phenol and chloroform in the presence of β-cyclodextrin [D-Falmaty, p. 467 (1978)] and the separation of the salicylaldehyde produced, for example by steam distillation, gives p-hydroxybenzaldehyde. That o-hydroxybenzaldehyde and p-hydroxybenzaldehyde are obtained by reacting chloroform with phenol and sodium hydroxide / methanol solution (U.S. Pat. No. 3,365,500), reducing and aminating m-nitrobenzaldehyde and then diazotizing M-hydroxybenzaldehyde is obtained by hydrolysis and hydrolysis [Organic Synthesis Vol. 3, p. 453 (1955)], and p-hydroxybenzaldehyde is obtained by oxidizing cresol with oxygen in the presence of a cobalt compound and a base. Are possible (JP 55-81832 JP), etc. are known.

However, in the method, the starting material is difficult to obtain, in the method, a mixture of isomers is formed, and in the method, there is a significant environmental pollution when carried out industrially. Low, a mixture of isomers is formed, the method has a low volume yield because the diazotization reaction is performed at a low concentration, and the method requires the use of a cobalt-based, copper-based, nickel-based catalyst, etc. It has disadvantages such as requiring an operation for removing the raw material cresol and oxidized carboxylic acid remaining in the liquid.

B) Structure of the Invention (Problems to be Solved by the Invention) The present invention is to solve the above-mentioned conventional problems of synthesis and to obtain a high-purity and high-purity p- or m-hydroxybenzaldehyde by an easy operation. It does not provide a manufacturing method.

(Means for Solving the Problems) The present inventors have intensively studied to solve the above-described problems of the conventional technology. As a result, p- or m-hydroxybenzaldehyde can be prepared without requiring a purification step.
An industrially advantageous synthesis method with easy operation, high purity and high yield was found. That is, the gist of the present invention is the general formula The p- or m-tert-butoxybenzaldehyde represented by is reacted with a detert-butylating agent, or a detert-butylation catalyst is added and isobutylene by-produced under reduced pressure is distilled out of the reaction system. General formula And a method for producing p- or m-hydroxybenzaldehyde.

Next, the debutylation reaction route of the compound of formula (II) will be described.
The by-products derived from the tert-butyl group to be eliminated vary depending on the type of tert-butylating agent or de-tert-butylation catalyst and the method of use, but these by-products are recovered as tert-butylation reagents. Can be used.

As the de-tert-butylating agent, hydrochloric acid, a mineral acid such as sulfuric acid, hydrogen chloride, or as a de-tert-butylating catalyst,
Non-volatile acids such as p-toluenesulfonic acid, methanesulfonic acid, and strongly acidic ion-exchange resins are exemplified.

Method (A) Method (B) Method (C) First, the compound of formula (II) as a raw material of the compound of formula (I) is a known compound, and is a commercially available product or a compound of formula (II) obtained by distilling off the solvent obtained in Reference Production Examples 1 and 2 described below. A residue containing the compound may be used. The compound of formula (II) obtained in this manner is subjected to the de-tert-protection of the following methods (A) to (C).
-It may be used for the butylation reaction.

Method (A) Hydrochloric acid at a concentration of 35% is added to the compound of formula (II) in a molar amount of 1 to 5 times, preferably 2 to 3 times the molar amount of the compound of formula (II), and the mixture is added at room temperature for 1 to 2 hours. Stir. After completion of the reaction, the reaction solution is extracted with a suitable solvent such as tetrahydrofuran, benzene, toluene, chloroform and the like. After separating the organic layer, the organic layer is washed with an aqueous solution of 1 to 5% sodium hydroxide or an aqueous solution of 1 to 5% sodium carbonate, and the solvent is distilled off. Benzaldehyde is obtained.

Method (B) By reacting the compound of the formula (II) with sulfuric acid at a concentration of 30 to 50% according to the method (A), the desired compound of the formula (I) is obtained, and at the same time, tert-butyl alcohol is obtained. By-produce.

Method (C) Paratoluenesulfonic acid was added to the compound of formula (II) in a catalytic amount.
When 0.001 to 0.01 equivalents are added and the reaction is carried out under reduced pressure while heating to 40 to 60 ° C., the tert-butyl group is eliminated, isobutene is distilled off, and the desired compound of the formula (I) is introduced into the system. can get.

Examples 1 to 6 show synthesis examples by the methods (A) to (C).

Example 1 Synthesis of p-hydroxybenzaldehyde [Method (A)] A 300 ml four-necked flask was equipped with a stirrer and a reflux condenser, and p-tert-butoxybenzaldehyde 4 was added thereto.
4.6 g (0.25 mol) and 52.1 g (0.50 mol) of 35% aqueous hydrochloric acid were added, mixed and stirred at room temperature for 1 hour to precipitate white crystals. After dissolving the crystals with chloroform, the aqueous layer was removed by extraction. Further, the organic layer was washed with a 2% aqueous solution of sodium carbonate (50 ml), and then concentrated to remove p.
-Hydroxybenzaldehyde 30.2 g (gas chromatography purity 100%, yield 99.0%) was obtained. Its melting point was 116 to 117 ° C., which was consistent with the melting point of the standard.

Example 2 Synthesis of m-hydroxybenzaldehyde [Method (A)] A 300 ml four-necked flask was equipped with a stirrer and a reflux condenser, and m-tert-butoxybenzaldehyde 4 was added thereto.
4.6 g (0.25 mol) and 65.2 g (0.625 mol) of 35% aqueous hydrochloric acid were added, mixed, and stirred at room temperature for 1 hour and 30 minutes to precipitate white crystals. Thereafter, the same operation as in Example 1 was performed, and m
30.1 g of hydroxybenzaldehyde (gas chromatography purity 100%, yield 98.6%) was obtained. The melting point of this product was 103 to 104 ° C, which coincided with the melting point of the standard.

Example 3 Synthesis of p-hydroxybenzaldehyde [Method (B)] A 500 ml four-necked flask was equipped with a stirrer and a reflux condenser, and p-tert-butoxybenzaldehyde 8 was added thereto.
When 2.9 g (0.465 mol) and 200 g (0.816 mol) of 40% aqueous sulfuric acid were added, mixed and stirred at room temperature for 1 hour, white crystals were precipitated. After dissolving the crystals with a dichloromethane solution, the crystals were extracted and the water tank was removed. Further, the organic layer was washed with a 2% aqueous sodium carbonate solution (100 ml) and then concentrated to obtain 55.8 g of p-hydroxybenzaldehyde (purity of gas chromatography 100%, yield 98.3%). Its melting point was 116-117 ° C.

Example 4 Synthesis of m-hydroxybenzaldehyde [Method (B)] A 500 ml four-necked flask was equipped with a stirrer and a reflux condenser, and m-tert-butoxybenzaldehyde 7 was added thereto.
6.8 g (0.431 mol) and 50% sulfuric acid aqueous solution, 145 g (0.740 mol)
Was added and the mixture was stirred at room temperature for 1 hour to precipitate white crystals. Thereafter, the same operation as in Example 1 was performed to obtain 51.8 g of m-hydroxybenzaldehyde (gas chromatography purity: 100%, yield: 98.4%). Its melting point was 103-104 ° C.

Example 5 Synthesis of p-hydroxybenzaldehyde [Method (C)] A 300 ml four-necked flask was equipped with a stirrer and a reflux condenser, and p-tert-butoxybenzaldehyde 1 was added thereto.
7.8 g (0.10 mol) and 0.086 g of paratoluenesulfonic acid
(0.5 mmol), and the mixture was stirred at 50 ° C. for 1 hour while reducing the pressure to 20 to 25 mmHg, whereby white crystals were precipitated. The crystals are dissolved in a mixed solution of tetrahydrofuran and toluene, washed with water and concentrated to obtain 11.9 g of p-hydroxybenzaldehyde (purity 100% by gas chromatography, yield 9).
7.5%). Its melting point was 116-117 ° C.

Example 6 Synthesis of m-hydroxybenzaldehyde [Method (C)] A 30-volume four-necked flask was equipped with a stirrer and a reflux condenser, and 26.7 m-tert-butoxybenzaldehyde was added thereto.
g (0.15 mol) and 0.258 g (1.5
Mmol), and the mixture was stirred at 50 ° C. for 1 hour while reducing the pressure to 20 to 25 mmHg, whereby white crystals were precipitated. afterwards,
The same operation as in Example 5 was performed, and 17.5 g of m-hydroxybenzaldehyde (gas chromatography purity 100%,
Yield 95.6%). Its melting point is 103-104 ℃
Met.

Reference Production Example 1 Synthesis of p-tert-butoxybenzaldehyde A 500 ml four-necked flask was equipped with a stirrer and a reflux condenser, and p-tert-butoxybenzchloride 9 was added thereto.
2.3 g (0.50 mol), 18.2 g of a piece of magnesium metal and 200 ml of anhydrous tetrahydrofuran were added and reacted to obtain p-ter.
Prepare a solution (0.50 mol) of t-butoxyphenylmagnesium chloride. Here is dimethylformamide
36.5 g (0.50 mol) was added dropwise while maintaining the temperature at 35 ° C.
Stirring was continued for another hour. After completion of the reaction, the reaction solution is cooled to room temperature, and 400 ml of saturated aqueous ammonium chloride is added to hydrolyze. Thereafter, the organic layer was separated, and the organic layer was concentrated and distilled under reduced pressure to obtain 82.9 g of p-tert-butoxybenzaldehyde (purity of gas chromatography: 100%).
%, Yield 93.0%).

Its analysis values and physical properties were as follows.

(1) Elemental analysis value C ₁₁ H ₁₄ O ₂ Theoretical value C% = 74.12 H% = 7.93 Actual value C% = 74.53 H% = 7.95 (2) Boiling point 92 ° C / 2mmHg (3) IR spectrum (NaCl) cm ^-1 2970,2930,2815,2720,1670,1570,1365,890,830,620 (4) NMR spectrum (CDCl ₃ ) δ 1.25 (9H, S), 6.93 (2H, d, J = 6Hz) 7.61 (2H, d, J = 6 Hz), 9.72 (1H, S) Reference Production Example 2 Synthesis of m-tert-butoxybenzaldehyde A 500-ml four-necked flask was equipped with a stirrer and a reflux condenser, and m-tert-butoxybenzbromide 11 was added thereto.
4.6 g (0.5 mol) was added, and the same operation as in Reference Production Example 1 was carried out to obtain 76.8 g of m-tert-butoxybenzaldehyde.
(Gas chromatography purity 100%, yield 86.2%).

Its analysis values and physical properties were as follows.

(1) Elemental analysis value C ₁₁ H ₁₄ O ₂ Theoretical value C% = 74.12 H% = 7.93 Actual value C% = 74.10 H% = 7.90 (2) Boiling point 91 ° C./3 mmHg (3) IR spectrum (NaCl) cm ^-1 2970,2925,1650,1575,1250,1160,850,780,680 (4) NMR spectrum (CDCl ₃ ) δ 1.28 (9H, S), 7.00 to 7.44 (4H, m) 9.76 (1H, S) Effects According to the production method of the present invention, a compound of formula (I) useful as an intermediate of a medicinal and agricultural chemical can be obtained in a higher yield by a simple reaction operation than in a conventional synthesis method.

Furthermore, even if a residue obtained by distilling off the solvent containing the compound of formula (II) is used as a raw material for the detert-butylation reaction, the compound of formula (I) requires another purification step such as distillation and recrystallization. High-purity product can be obtained.

Therefore, the present invention is useful as an industrial synthesis method of the compound of the formula (I).

Claims (1)

(57) [Claims] (1) General formula The p- or m-tert-butoxybenzaldehyde represented by is reacted with a detert-butylating agent, or a detert-butylation catalyst is added and isobutylene by-produced under reduced pressure is distilled out of the reaction system. General formula A method for producing p- or m-hydroxybenzaldehyde represented by the formula: