JPS5849329A - Preparation of cyclohexanone dimethyl acetal - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as a raw material of drug, in high purity and yield, by reacting cyclohexanone with methanol in the presence of calcium chloride as dehydrating agent under acidic conditions, adding a hydrazine compound to the resultant reaction liquid, and purifying the product by distillation. CONSTITUTION:Cyclohexanone dimethyl acetal is prepared by reacting cyclohexanone with methanol under acidic condition with an acid such as sulfuric acid, hydrochloric acid, etc. in the presence of calcium chloride as a dehydrating agent. A hydrazine compound (e.g. methylhydrazine) is added to the reaction mixture, and distilled to obtain a highly purified cyclohexanone dimethyl acetal. The amount of calcium chloride is preferably about 1/3-2mol per 1mol of cyclohexanone.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing cyclohexanone dimethyl acetal (hereinafter abbreviated as CD-ketal), which is useful as a raw material for pharmaceuticals. To be more specific, is calcium chloride used as a dehydrating agent when reacting cyclohexanone and methanol? A method for producing high-purity CD-ketal, which involves adding hydrazine to the reaction solution obtained by the method and distilling and purifying it. For example, cyclohexanone and methanol can be reacted with sulfuric acid, hydrochloric acid, etc. as a catalyst, or cyclohexanone and methanol can be reacted with an acid catalyst, sulfuric acid steel, and gold.
It was manufactured by a reaction method. However, this reaction is an equilibrium reaction, and only water is produced during the reaction. It is difficult to remove it from the reaction system, so the yield is low.
Isolation of the product by fractional distillation is also useful for cyclohexanone and CD-
Due to the small difference in boiling point from ketal, it was extremely difficult to industrially produce high-purity products.

The present inventors have made extensive studies to find a method for industrially obtaining high-purity CD-ketal at a high yield, and have dramatically increased the yield by using calcium chloride as a dehydrating agent. Hydrazine in the termination liquid? Is it a high purity product due to Jj k and fractional distillation? It has been made possible and achieved by the present invention to provide this.

What is the reaction between xanone and methanol, cyclohexanone, methanol, and chloride? The mixture is mixed, the reaction mixture is made acidic with an acid such as sulfuric acid or hydrochloric acid, and the reaction is carried out at around room temperature. Preferably, an excess of methanol/chlorhexanone is used. The amount of calcium chloride used is t per 1 mole of cyclohexanone.
It is preferable to use about 1/3 to 2 mol. If it is used more than this, there will be no significant effect, and if it is less than this, the effect will be slightly reduced. By adding hydrazines to the reaction-completed liquid and fractionating the oil layer, CD-ketal and hydrazone can be easily separated and highly pure CD-ketal can be obtained. As the hydrazines, for example, hydrazine hydrate, methylhydrazine, phenylhydrazine, etc. can be used without any problem, and they can be added directly to the reaction completed solution and added for 1 portion of neutralization, or added after 1 portion of neutralization. There is absolutely no problem.

As mentioned above, the method of the present invention makes it possible to industrially provide high-yield, high-purity CD-ketal, and thus makes an extremely large contribution to this industry.

The present invention will be further explained with reference to Examples below. In the examples, parts expressed are parts by weight.

Reference example 1゜58 parts of methanol and 35 parts of cyclohexanone! : Mix 40 parts of chloride and 15 parts of concentrated sulfuric acid. 20
After reacting at ~30°C for 8 hours, the mixture was neutralized with a solution of 12 parts of caustic soda dissolved in 200 parts of methanol, boiled in 90 parts of water, washed with water, and then separated to obtain 43 parts of an oil layer. By vacuum distillation,
38 parts of a fraction at 32 mmHg and 70 to 80°C were obtained. The CD-ketal content by gas chromatography was 88%. For comparison.

An experiment using copper sulfate instead of calcium chloride on the same strip gave 34 parts of a product with a gas chromatography content of 47%.

Example 1 25 parts of methanol, 18 parts of cyclohexanone, 8 parts of calcium chloride, and 5 parts of concentrated hydrochloric acid are mixed.

After reacting at 10 to 25°C for 10 hours, the mixture was neutralized with a solution of 2 parts of caustic soda dissolved in 40 parts of methanol.

40 parts of water was added, and after washing with water, the liquid was separated to obtain 22 parts of an oil layer.

After adding 4 parts of 80% hydrazine hydrate and separating the liquid, the oil layer is distilled under reduced pressure. 15 parts of a fraction at 30 mmHg and 69 to 72°C were obtained. The content determined by gas chromatography was 99.3%.

Patent Applicant: Wako Pure Chemical Industries, Ltd., Company 5 - Procedural Amendment May 24, 1980 Commissioner of the Patent Office 1. Indication of the Case Patent Application (3) filed on April 26, 1980 2. Name of the invention Cyclo Process for producing hexanone dimethyl acetal 1 Relationship with the case of the person making the amendment Patent applicant zip code 54 Contact information Patent! ! (Tokyo) 03-270-8
5715, Detailed description of the invention in the specification subject to amendment.

6. Add the following sentence after "is obtained." written on page 3, line 15 of the specification of contents of the amendment.

``As a result, CD-ketal was easily separated with high purity without azeotrope with hydrazone, which is a problem.In this case, as a distillation apparatus,
No particularly precise fractionation equipment is required; an existing simple distillation equipment is sufficient. Also used here. "that's all

Claims (1)

[Claims] (1) Calcium chloride as a dehydrating agent? Cyclohexanone dimethyl acecool obtained by reacting clohexanone, methanol, and gold in an acidic environment, and hydrazines? In addition, the method for producing high-purity cyclohexanone dimethyl acecool is characterized by distillation and purification.