Sulfuric Acid → 6-fluoro-2,3-dihydro-4H-1-benzopyran-4-one

참여 물질

반응 단계

In the former pathway, 3-(4-fluorophenoxy)propionitrile having the formula (I) is stirred in polyphosphoric acid at a temperature of more than 140° C., preferably at about 170° C. for about 15 minutes to form 6-fluoro-4-chromanimine having the formula (V) and then the reaction mixture is poured into ice-water to hydrolyze 6-fluoro-4-chromanimine having the formula (V) into 6-fluoro-4-chromanone having the formula (II). Though this pathway comprises a short and simple step, it accompanies the side reaction with coloration. In the latter pathway, 3-(4-fluorophenoxy)propionitrile having the formula (I) is hydrolyzed with acid such as hydrochloric acid, hydrobromic acid and sulfuric acid into 3-(4-fluorophenoxy)propionic acid having the formula (IV). When hydrobromic acid or sulfuric acid is employed in a high concentration in order to increase the rate of hydrolysis reaction, an unfavourable side reaction such as cleavage of the ether bond and sulfonation of the aromatic ring may occur. On the other hand, when hydrochloric acid is employed, such side reaction as mentioned above does not occur. Concentrated hydrochloric acid is preferably used from the view point of the reaction rate and yield and 3-(4-fluorophenoxy)propionitrile having the formula (I) is refluxed in the concentrated hydrochloric acid for 10 hours to give 3-(4-fluorophenoxy)propionic acid having the formula (IV) in a quantitative yield. Cyclization of 3-(4-fluorophenoxy)propionic acid having the formula (IV) into 6-fluoro-4-chromanone having the formula (II) can be carried out in a good yield by known method where the compound (IV) is stirred in polyphosphoric acid at 100° C. for 10 minutes (U.S. Pat. Nos. 4,117,230 and 4,130,714), or by the method where the compound (IV) is treated in concentrated sulfuric acid. If the condition of acid hydrolysis and ring closure reaction is agreed, 6-fluoro-4-chromanone having the formula (II) can be obtained in an almost quantitative yield from 3-(4-fluorophenoxy)propionitrile having the formula (II). When 3-(4-fluorophenoxy)propionitrile having the formula (I) is stirred in 85 to 95% sulfuric acid at 90° C. for 10 hours, hydrolysis reaction and ring closure reaction occur simultaneously and thus 6-fluoro-4-chromanone having the formula (II) can be obtained directly. In this reaction, however, by-product such as 3-(4-fluorophenoxy)propionic acid is formed and the yield is quite low.

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