A Selective Conversion of Nitriles into Carboxamides by Formic Acid

Abstract

The thiocarbonyl group of N-acylated cyanothioformamides exhibits pronounced dienophilic reactivity. Thus, with a variety of 1,3-dienes, we obtained the corresponding Diels-Alder adducts 1 [1].Investigating possible transformations of adducts 1, we observed that dissolving them in concentrated formic acid at room temperature resulted in a specific conversion of the nitrile moiety into the corresponding carboxamides 2a -e,g,h with concomitant formation of one mole of carbon monoxide. In most cases, the reaction was complete within 15 -20 minutes and the amides could be isolated in 22 -94% yield (Scheme1). Abstract. Aliphatic α-(acylamino)nitriles react with formic acid at room temperature to give the corresponding α-(acylamino)carboxamides with concomitant formation of one mole of carbon monoxide. This new reaction, which was first observed with 2-acylamino-2-cyano-3,6-dihydro-2H-thiapyIn contrast to reported conversions of nitriles into carboxamides by formic acid which require either heating at 180 -200 °C [2], or the presence hydrogen halides [3], our reaction occurs under rather mild conditions. In order to determine the structural features essential for this conversion and to study its scope, several other α-aminonitriles were treated with formic acid at room temperature. Neighbouring GroupBecause the two α-aminonitriles 1f and 1i [1], both lacking the N-acyl functionality present in the other members of the group, were not altered by formic acid at room temperature, we came to the conclusion that the N-acyl group is essential for the reaction and that other special features such as the thioether moiety present in the Diels-Alder adducts 1 are no prerequisites for the reaction. Accordingly, N-(cyanomethyl)benzanilide (3) [4] after 3 h gave the corresponding acetamide 4 in 93% yield together with 0.9 equivalents of carbon monoxide. The two cyano groups in N,N-bis(cyanomethyl)benzamide (5) [5] could also be converted into carboxamido groups, affording the triamide 6 in 74% yield. In this case, measured by the rate of carbon monoxide evolution, the conversion of the first nitrile needed about 16 h, whereas the whole reaction was complete after about 64 h (Scheme 2).Whereas compounds 1, 3 and 5 on treatment with formic acid yielded the corresponding amides, 2-(Nphenylbenzamido)isobutyronitrile (7) [6], the only other nitrile without α-hydrogen atoms studied, afforded 83% of acid 8 together with only 5% of amide 9.In a one-pot reaction α-(N-formyl)carboxamides 11a -c could be synthesized from α-aminonitriles 10a -c usranes 1, can also be used to convert other N-(α-cyanoalkyl) amides such as N-cyanomethylbenzamides 3, 5 and the 3,4-dihydro Reissert compound 16 into the corresponding carboxamides. Another application is a synthesis of 2-formylaminoacetamides 11. A mechanism for the reaction is proposed.