Process for the preparation of 5-Carboxyphthalide

Abstract

There is described a process for the preparation of 5-carboxy phthalide, which comprises adding terephthalic acid to fuming sulfuric acid containing at least 20% of SO3, then adding formaldehyde to the mixture, heating the mixture at a temperature of 120-145° C. and isolating 5-carboxyphthalide from the reaction mixture.

Description

FIELD OF THE INVENTION[0001]The present invention concerns a process for the preparation of an isobenzofuran derivative. More particularly, the invention refers to a process for the preparation of 1-oxo-1,3-dihydro-5-isobenzofurancarboxylic acid.[0002]1-Oxo-1,3-dihydro-5-isobenzofurancarboxylic acid, hereinbelow simply also referred to as 5-carboxyphthalide, represented by the formula A,is a useful intermediate in the preparation of several chemical compounds, particularly dyes, resins and drugs. In particular, 5-carboxyphthalide is an intermediate useful in the synthesis of citalopram, a well-known antidepressant drug, whose preparation using said intermediate is described in the International Patent Application WO 00023431 and in the corresponding Italian Patent Application IT1999 MI 0001724, whose contents are incorporated by reference herein.BACKGROUND OF THE INVENTION[0003]It is known that 5-carboxyphthalide may be prepared by reduction of one of the carbonyl groups of trimelli...

AI Technical Summary

Benefits of technology

[0009]It has now surprisingly found that, by addition of terephthalic acid to fuming sulfuric acid (oleum) containing at least 20% of SO3, by subsequent addition of formaldehyde to the mixture and by heating, 5-carboxyphthalide is obtained in good yields and in a high degree of purity under easily controllable conditions, in open and however not pressurized reactors, and without any risk in handling the reaction mixtures.

[0010]Thus, the present invention provides, according to a method of simple execution, a process for the preparation of 5-carboxyphthalide of formula A, which comprises adding terephthalic acid of formula Ito fuming sulfuric acid containing al least 20% of SO3, subsequently adding formaldehyde thereinto, heating the mixture at 120-160° C. and isolating the obtained 5-carboxyphthalide.

Problems solved by technology

This method has the drawback of giving a 5-carboxyphthalide containing, as a by-product, the 6 isomer in an amount which can reach 10%.

This synthesis must be carried out very cautiously whereby it is not suitable for the industrial scale-up owing to the problems connected to the use of liquid sulfur trioxide.

Nevertheless, the reaction mass remains in any case thick and, therefore, involves a difficult handling for the recovery of the end product.

Reaction conditions like these, however, are not suitable for the industrial scale because pressure reactors and strong acidity conditions are required.

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