CS257248B1 - Process for the preparation of 2- (2'-furyl) -benzimidazole - Google Patents

Abstract

The solution concerns a method of preparing 2-(2'- furyl)-benzimidazole, which due to its fungioid properties is used for seed dressing against fungal diseases. The substance is prepared by the reaction of o-phenylenediamine and furfural bisulfite with the addition of mineral acids, then 2-(2'-furyl)-. -benzimidazole is released from its salt with the appropriate mineral acid by neutralization in the presence of a solvent miscible with water at a certain temperature. The procedure achieves a higher yield compared to the procedures used so far.

Description

The present invention relates to a process for the preparation of 2- (2'-furyl) -benzimidazole (fuberidazole) which, for its fungicidal properties, is used for dressing seed against fungal diseases.

The preparation of 2- (2'-furyl) -benzimidazole is reported by D. Jerchel, H. Fischer and M. Kracht (Ann. 575, 162 (1952)), FF Stephens and JD Brower (J. Chem. Soc., 1922). 1952), R. Weidenhagen / Ber.

263 (1936)]. A disadvantage of these processes is the difficult oxidation of Schiff's base o-phenylenedlamine with furfural, difficult product isolation and low yields. The preparation of 2- (2'-furyl) -benzimidazole by reaction of imidoesters with o-phenylenediamine is reported by R. C. De Selms (J. Org. Chem. 27, 2163 (1962)). A method for preparing 2- (2'-furyl) -benzimidazole by reacting o-phenylenediamine with furfural bisulfite is described by H. F. Ridley,

R.G.W. Spickett and G.M. Tommis (J. Heterocyclic Chem., 2, 453 (1965)). A modification of this procedure is reported by J. Frgal and J. Nicodem (AO 223 348).

The disadvantage of this method is the use of a large excess of sodium metabisulphite, a relatively low reaction yield (max. 65-75%), a large amount of difficult-to-treat waste and unpleasant exhalation.

The above-mentioned disadvantages are substantially reduced by the process for the preparation of 2- (2'-furyl) -benzimidazole by reaction of o-phenylenediamine with furfuralbisulfite according to the invention, which comprises adding a mineral acid such as sulfuric acid, hydrochloric acid or sulfur dioxide to the reaction mixture. whereupon the 2- (2'-furyl) -benzimidazole is liberated from its salt with the appropriate mineral acid by neutralization, for example sodium or potassium hydroxide, sodium, potash or ammonia, in the presence of a water-miscible solvent such as methanol , ethanol, propanol, isopropanol or acetone at 30 to 100 ° C. By stabilizing o-phenylenediamine, the yield is increased by 15 to 20 t, the sodium bisulfite feed is reduced, unwanted exhalation is suppressed and waste treatment is simplified.

The beneficial effect of mineral acid stabilization of o-phenylenediamine on the reaction yield increases in the series - bisulfite - sulfuric acid - sulfuric acid - hydrochloric acid. While a yield of about 50% of the o-phenylenediamine used was obtained with sodium bisulfite stabilization, the reaction yield using hydrochloric acid was about 95%. The purity of the product increases in the same order. The reaction can also be carried out in an aqueous or aqueous-alcoholic medium, optionally in a mixture of water and an aromatic hydrocarbon (e.g. toluene), in order to bind the impurities. The process according to the invention consists in adding the appropriate mineral acid (sulfur dioxide, hydrochloric acid, sulfuric acid) to the o-phenylenediamine suspension, and then adding a solution of furfural bisulfite in water at 0 to 100 ° C.

The reaction rate is temperature dependent and at the end of the addition of the furfuralbisulfite solution, 2- (2'-furyl) -benzimidazole begins to precipitate as a salt with the appropriate mineral acid.

Upon completion of the reaction, 2- (2'-furyl) -benzimidazole is liberated from its salt by addition of an equivalent amount of base (sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia). In order to obtain a suitable crystalline form, it is preferred to carry out neutralization in the presence of solvents such as methanol, ethanol, propanol, acetone at a higher temperature to form a concentrated solution from which fuberidazole crystallizes.

After cooling the reaction mixture, the product is isolated by filtration and washed with water, optionally with a small amount of acetone, toluene or aqueous alcohol.

In addition to the stabilization of o-phenylenediamine, the presence of an acid also has a catalytic effect on the reaction. While almost no fubridazole was obtained in the test for the preparation of fuberidazole at a molar ratio of o-phenylenediamine to furfural to sodium metabisulfite of 1: 1.125 to 0.586, pure fuberidazole was obtained in 50% yield at the same ratio of raw materials and 0.015 mol of hydrochloric acid.

The method according to the invention is further explained in the following examples.

Example 1

A 250 ml, three-necked flask equipped with a stirrer and a heated water bath was charged with 40 ml of ethanol, 10 ml of concentrated hydrochloric acid and 14 g of o-phenylenediamine. The reaction mixture was allowed to warm to 50 ° C and a furfural bisulfite solution of composition was added over 2 hours via a metering pump.

ml water, 14 g furfural and 14 g sodium metabisulfite. The rate of dosing was variable; about 1/2 of the solution was added over 15 minutes, another 1/4 over 0.5 hours and the last quarter of the solution over 75 minutes. The reaction mixture was then stirred for 4 hours at 50 ° C and then neutralized over 1 hour with solid sodium hydroxide to a pH of about 7. Then, with slow cooling, stirred for a further 4 hours. The filtered product is washed on a frit with 25 ml of 50% ethanol and 100 ml of water. 20.5 g of white fuberidazole (85.9% on o-phenylenediamine) of m.p. 282-286 ° C).

Example 2

Apparatus as in Example 1. 50 ml of ethanol, 10 ml of water and 14 g of o-phenylenediamine are introduced. 6 ml of sulfuric acid (65%) are added dropwise with stirring. A thick, white, very difficult to stir slurry formed. The temperature spontaneously rose to 40 ° C. Then heated to 50 ° C and dosed with a solution of furfural bisulfite of 35 ml water, 14 g sodium metabisulfite, 14 g furfulal for 3 hours. The rate of addition was similar to that of Example 1. After the solution was dosed, the reaction mixture was stirred at 55 ° C for 2 hours and then neutralized and isolated in the same manner as in Example 1. 20.36 g of fuberidazole (85.3% per second) were obtained. phenylenediamine) mp Mp 288-292 ° C.

Claims (1)

A process for the preparation of 2- (2'-furyl) -benzimidazole by reaction of o-phenylenediamine and furfuralbisulfite, characterized in that a mineral acid such as sulfuric acid, hydrochloric acid, or sulfur dioxide is added to the reaction mixture, followed by 2- (2'-). furyl) -benzimidazole is liberated from its salt with an appropriate mineral acid by neutralization, for example sodium or potassium hydroxide, sodium, potash or ammonia, in the presence of a water-miscible solvent such as methanol, ethanol, propanol, isopropanol or acetone at 30 ° C to 100 ° C.