JPS60215681A - Production of phthalide - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as a raw material for the production of pharmaceuticals, etc., nearly quantitatively, in high purity, without producing by-products, by carrying out the catalytic hydrogenation of phthalic anhydride in an inert solvent in the presence of a ruthenium complex catalyst at a temperature within a specific range. CONSTITUTION:The objective compound can be produced by the catalytic hydrogenation of phthalic anhydride in the presence of a ruthenium complex catalyst of formula (X is H, Cl, etc.; n is 0-2; when n is 2, plural Xs may be same or different; L is CO, etc.; y is 0-3; when y is 2 or 3, plural Ls may be same or different; R is 1-15C alkyl, etc.; x is 1-4), in an inert solvent at 160-210 deg.C. EFFECT:The objective compound can be separated and purified easily, and the process is extremely excellent from the industrial viewpoint.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing phthalides. Specifically, the present invention relates to a method for producing highly pure phthalide with almost no by-products by hydrogenating phthalic anhydride using a ruthenium complex as a catalyst. Phthalides are highly valuable compounds as raw materials for manufacturing medicines, agricultural chemicals, dyes, etc.

It is known that siphthalide is produced by hydrogenation of phthalic anhydride using a ruthenium complex as a catalyst; for example, U.S. Pat. No. 3,957,827 and J. Chem.
, 8oc, Chem, Commun, , 412
= described on page 3 (1975). However, according to this method, a large amount of 7-thalic acid is produced as a by-product, and the yield of phthalide is about 60% based on phthalic anhydride.
This is not fully satisfactory as an industrial manufacturing method.

That is, the synthesis of phthalide by the hydrogenation reaction of phthalic anhydride is thought to proceed as shown in the following equation, in which 1 mole of phthalide is produced from 1 mole of phthalic anhydride, and 1 mole of phthalide is produced from 1 mole of phthalic anhydride. Water is produced as a by-product, and this by-produced water reacts with unreacted phthalic anhydride in the system to produce phthalic acid as shown in the following formula. This is because the production yield of phthalide is suppressed due to the by-product of this phthalic acid. This is reflected in the above-mentioned U.S. Patent No. 3,957.
, No. 827, [When 1 mol of starting material is reduced, 1 mol of water is produced as a by-product, and this water reacts with the starting material to form the corresponding acid, so the produced lactone is A 50% yield based on the amount of starting material charged is a theoretical yield of 10
It is expressed as 0chi. ”, and furthermore, the above-mentioned J, Chem, 8oc, Chem,
Commun, .

According to a report on pages 412-3 (1975), the conversion rate of phthalic anhydride was ioo%, the phthalide yield was 59.3%, and the by-product phthalic acid was 40.7%. In the known method of synthesizing phthalide from phthalic anhydride using a ruthenium complex catalyst, the by-product of phthalic acid is unavoidable, and it is said that it is difficult to obtain 7-thalide in a higher yield than this. It was.

The present invention aims to overcome these difficulties and provide an industrially practicable method for producing phthalides. Specifically, the object of the present invention is to provide a method for producing phthalide in high yield by using phthalic anhydride as a raw material and suppressing the by-product of phthalic acid.

As a result of various studies for the above purpose, the present inventors found that phthalic anhydride was dissolved in an inert solvent in the presence of a ruthenium complex catalyst.
The present invention was completed based on the discovery that catalytic hydrogenation at 60 to 210°C allows phthalide to be obtained in high yield without the by-product of phthalic acid.

In carrying out the present invention, the influence of the reaction temperature is large, and 16
It is necessary to carry out the reaction at 0 to 210°C. Although the reaction proceeds even at a reaction temperature lower than 160° C., the reaction rate is slow and the by-product of phthalic acid cannot be avoided. 21 more
A reaction temperature higher than 0° C. is not preferable because decomposition of the catalyst is observed.

The ruthenium complex used in the present invention is [RuXn(
PRs)xLY ], where X
As hydrogen, chlorine, bromine, iodine or carbon number 1~
4 alkyl group, n is an integer of O to 2, and n is 2
In the case of , X may be the same or different.

L represents an olefin or a carbonyl group (CO), y is an integer of O to 3, and when y is 2 or 3, they may be the same or different. R has 1 or more carbon atoms
15 alkyl group, aryl group or benzyl group, and X is an integer of 1 to 4. Examples of such ruthenium complexes include RuClt (PPhs)s (Ph represents Hue=7t, a group), RuHC/(PPhs)s, RuHCA!
(CO)(PPhs)s, RuCA! 2 (PBus)
s (Bu represents a butyl group), RuBr 2 (P
Pha)s etc.

The amount of catalyst used is such that the ratio of the ruthenium complex to the raw material phthalic anhydride is 0.01 to 1 mol, preferably 0.01 to 1 mol.
02 to 0.6 mol. Although the reaction will proceed even if the amount used is as small as 0.01 mol, the reaction rate will be slow. Further, using a catalyst amount greater than 1 mole has no further effect.

The higher the hydrogen pressure used in carrying out the present invention, the faster the reaction rate will be, but in the case of industrial production, particularly high pressure is not required, and from an economical point of view it is normal pressure to 50 kli/L/L.
CI! , preferably 5 to 30 kg/cd. The reaction time is not particularly limited, but is determined from an economical standpoint by considering the amount of catalyst, reaction pressure, reaction temperature, etc., and is usually in the range of 0.1 to 20 hours, preferably 0.5 to 10 hours. It is.

The inert solvent used is not particularly limited, but hydrocarbon solvents, particularly aromatic hydrocarbon solvents such as benzene, toluene, xylenes, and fluid cumene are suitable.

After the reaction, the precipitated phthalide is separated, and the liquid can be reused as a catalyst-containing solution.

The method for producing phthalide of the present invention involves catalytic hydrogenation of phthalic anhydride, whereby phthalide can be produced almost quantitatively with high purity without the by-product of phthalic acid.

It is an extremely excellent industrial production method that can be easily separated and purified.

Specific examples of the present invention are shown below.

Example 1 In a 100 d autoclave equipped with an electromagnetic vertical stirrer, 10.0 IF (67.5 mmol) of phthalic anhydride as a raw material, 30 RuC12 (PP h 3) as a catalyst,
096 f (0.10 mmol) and 4 oml of pseudocumene as a solvent were prepared, and 20 kg/
A hydrogen pressure of dtG was applied. While stirring, when the temperature reached 170° C., the pressure was adjusted to 3 o kglcrla.

The reaction was carried out at 170°C for 5 hours. As the reaction progressed, a decrease in pressure was observed, so the reaction pressure was 2.
Add hydrogen gas to 5 when it reaches 9/cJ to make 3 ok
/i.

After the reaction was completed, the mixture was cooled to room temperature, and then the pressure was decompressed.

Since the reaction solution contains white crystals, it was filtered for about 10 d.
of pseudocumene. When this white crystal was dried under reduced pressure, 5271 was obtained.

This white crystal showed a melting point of 73.5°C, elemental analysis showed that the carbon content was 71.98% and the hydrogen content was 4.54%, and the infrared absorption spectrum and nuclear magnetic resonance spectrum charts matched those of phthalide. . Furthermore, no peak other than phthalide was detected in analysis by gas chromatography.

On the other hand, when the P solution obtained by the above filtration was analyzed by gas chromatography, it was found that it contained 3.77r 7-thallide, but no peak of phthalic anhydride was detected.

As a result, c+, o4f (67.4 mmol) of phthalide was produced, which corresponded to a yield of 99.9 molti based on the charged phthalic anhydride.

(Conversion rate of phthalic anhydride: 100%, selectivity of phthalide: 999%) Comparative Example 1 The same procedure as in Example 1 was conducted except that the reaction temperature was 150°C. The obtained crystals of 3,619 and the r liquid were analyzed. As a result, the crystals form phthalide 2.
52S', phthalic anhydride 0.25f1 phthalic acid 0831
On the other hand, the f-liquid contains 3.53f of phthalide.
1 phthalic anhydride and 2.3 Of.

As a result, 6.0 s t (45.1 mmol) of phthalide was produced, which corresponds to 66.8 molti based on the phthalic anhydride charged. (Conversion rate of phthalic anhydride 74.5%, selectivity of phthalide 89.7%) Example 2 The amount of catalyst was o, 048 t (o, o s mmol)
, the solvent was 401 nl of toluene, and the reaction temperature was 180 nl.
The reaction was carried out in the same manner as in Example 1, except that the temperature was changed to ℃. After the reaction was completed, the reaction solution was cooled and the pressure was released. Benzene was added to the reaction solution containing the obtained crystals to completely dissolve the crystals. analyzed.

As a result, 9.03 f (67.3 mmol) of phthalide was produced, which corresponded to a yield of 99.7 mol based on the charged phthalic anhydride.

Example 3 Catalyst amount: o, 240 t (0.2 s mmol), initial hydrogen pressure: 6 to 9/c! The reaction was carried out in the same manner as in Example 1, except that the reaction temperature was adjusted to 180 °C, and the reaction pressure was adjusted to 9/c/LG from 8 to 10, and the reaction liquid was treated after the reaction was completed. The same procedure as in Example 2 was carried out.

As a result of the analysis, 9.03 t (67.3 mmol) of phthalide was produced, and this phthalide yield was equivalent to 99.7 molti based on the charged phthalic anhydride.

Example 4 RuHCl(PPhs)3, RuH(J(C
o) (PPh, )3, RuC4(PBux)s, RuB
The reaction and analysis were carried out in the same manner as in Example 2, except that r2 (PPh3)3 was used, the amount used was 0.10 mmol, and the solvent was changed to O-xylev 40d. The results are shown in the table below.

Example 5 The same procedure as in Example 2 was carried out except that the amount of catalyst was 0.3 ast (o, as mmol) and the reaction time was 1.5 hours.

As a result, 9.02 t (67.2 mmol) II of phthalide was produced, which was equivalent to 99.6 molti based on the charged phthalic anhydride.

Patent applicant Nippon Shokubai Kagaku Kogyo Co., Ltd. Procedural amendment (voluntary) May 2, 1980 Dismissed Commissioner of the Patent Office Name Kazuo Sugi 1 Indication of case 1982 Patent Application No. 70026 2 Title of the invention Process for producing phthalides 3, Special amendment filed by the person applying for the amendment Applicant 5-1 Koraibashi, Higashi-ku, Osaka, Osaka Prefecture <462> Nippon Shokubai Kagaku Kogyo Co., Ltd. Representative Director San Ishikawa Department 4, Agent 〒-100 Tokyo Nippon Shokubai Chemical Co., Ltd., Tokyo Branch, 1-2-2 Uchisaiwai-cho, Chiyoda-ku, Tokyo 5, Section 6 of the detailed description of the invention in the specification of the application subject to amendment, Contents [1] Page 5, line 13 of the specification ``...or represents a carbonyl group (Co)...''
...or represents carbonyl (Co)..."

Claims (1)

[Claims] (11 General formula % formula %) (However, X represents hydrogen, chlorine, bromine, iodine, or an alkyl group having 1 to 4 carbon atoms, and n is an integer between θ and 2, and n is 2 In the case of , X may be the same or the same one. L represents an olefin or CO, y is an integer from θ to 3, and when y is 2 or 3, L represents a group, and X 1
It is an integer of ~4. ) is used as a catalyst to produce a phthalide by catalytic hydrogenation of phthalic anhydride in an inert solvent, the reaction temperature being 160 to 210°C. Law.