Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1991-06-07
1993-06-29
Dees, Jose G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
560 45, C07C22956
Patent
active
052236390
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for producing N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, a compound useful as a medicament for treating diseases caused by allergy, and more particularly to a process for producing the compound in a high yield in an industrially advantageous manner.
2. Description of Prior Art
N-(3',4'-dimethoxycinnamoyl)-anthranilic acid can be produced by various methods, including those in which 3',4'-dimethoxycinnamic acid or a derivative thereof is condensed with anthranilic acid or an ester thereof. Among hitherto known methods involving condensation are: condensed with anthranilic acid (see, e.g., Japanese Patent Publication No. 40,710/81 and Japanese Patent Application (Laid Open) No. 32,756/85); N-(3',4'-dimethoxycinnamoyl)-anthranilic is condensed with an ester of anthranilic acid, followed by the hydrolysis of the ester (see, e.g., Japanese Patent Publication No. 36,905/82); anthranilic acid or an ester thereof in the presence of a condensing agent (see, e.g., Japanese Patent Publication No. 48,545/83); and anthranilic acid in the presence of excess condensing agent to form [2-(3',4'-dimethoxystyryl)-3,1-benzoxazin-4-one] followed by the hydrolysis thereof (see, e.g., Japanese Patent Publication No. 3,995/84).
In processes A and B mentioned above, 3',4'-dimethoxycinnamic acid must be converted into a reactive derivative prior to condensation. The processes therefore require complicated operations. In addition, the processes involve a heating reaction during which by-products are formed through side reactions and decomposition of raw materials, and hence the yield of the desired compound becomes lower. There are even cases where a hardly separable by-product, 2-(3',4'-dimethoxystyryl)-3,1-benzoxazodin-4-one, is formed. In such cases, complicated purification steps are required. Process B, which utilizes an ester of anthranilic acid, is also disadvantageous in that it requires such additional steps as hydrolysis of the ester group and desalination with an acid.
Process C is advantageous in that there is no need for the conversion into a reactive derivative. However, when anthranilic acid is employed as a starting material and a condensing agent is used in around stoichiometric quantity, the desired compound could hardly be obtained because of undesirable side reactions. The process is therefore practiced by using a condensing agent in an amount less than stoichiometrically required, preferably ca. 0.4 times the quantity required stoichiometrically. It is therefore inevitable that the desired product can be produced at a low yield. In addition, by-products are still formed in large quantities including those which could hardly be separated, and hence the process requires complicated purification steps.
Process D was proposed as a method for overcoming such disadvantages. However, it is still unsatisfactory as an industrial process since the desired product could not be produced directly and hence complicated operation is required. In addition, the yield of the desired product is still not high owing to by-products.
DESCRIPTION OF THE INVENTION
The present inventors have conducted intensive studies in order to overcome the above disadvantages. As a result, it has now been found that the desired N-(3',4'-dimethoxycinnamoyl)-anthranilic acid can be obtained in a high yield by reacting 3',4'-dimethoxycinnamic acid with anthranilic acid in an aprotic polar solvent in the presence of an iminium salt and an inorganic salt, and that N-(3',4'-dimethoxycinnamoyl)-anthranilic acid so obtained can be purified quite easily since it is almost free from by-products.
Accordingly, there is provided by the present invention a process for producing N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, represented by Formula [I] of the following: ##STR1## which comprises reacting 3',4'-dimethoxycinnamic acid with anthranilic acid in an aprotic polar solvent in the presence of an inorganic salt and an iminium salt (Vilsmeir Reagent) formed
REFERENCES:
patent: Re32944 (1989-06-01), Harita et al.
patent: 4026896 (1977-05-01), Harita et al.
patent: 4337270 (1982-06-01), Noda et al.
patent: 4587356 (1986-05-01), Iizuka et al.
patent: 5049572 (1991-09-01), Scherrer et al.
Dees Jos,e G.
Frazier B.
Kohjin Co., Ltd.
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