Background: Earlier we found that the reaction of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-
2,3-dione (1) with primary aromatic amines, secondary aliphatic amines and N,N′-dinucleophiles
such as 1-aminoguanidine, guanidine, urea, and 1,2-phenylenediamine in ethanol or acetic acid at high
temperature gave the substituted thiophenes, amide and heterocyclic derivatives that have Nphenylthiocarbamoyl
group, respectively. As a part of our studies on the intermediate 1 in relation to
the synthesis of thioamides in aqueous medium, we now report the reactions of 1 with amines at room
temperature in the THF–H2O (1:1) system. The reaction of 1 with primary and secondary aliphatic
amines, N,N′-dinucleophiles such as hydrazine and guanidine and tertiary aromatic and aliphatic
amines led to 3-N-phenylthiocarbamoyl-2-butenamides 2a-n.
Method: In general, to a stirred solution of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione
(1) (1.0 mmol) in THF/H2O (1:1) was added each of the amines (1.0 mmol) (piperazine and DABCO
0.5 mmol) at room temperature. The reaction mixture was then stirred for 3-6 h. The progress of the
reaction was monitored by TLC (eluent AcOEt/hexane 2:1). The resulting solid was separated by filtration
and was recrystallized from a suitable solvent to give 2a-n. The structures of 2a-n were deduced
from their elemental analyses and IR, 1H, 13C NMR spectroscopic and mass spectrometric data.
Results: Reactions of 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione (1) with primary aliphatic
amines, N,N′-dinucleophiles such as hydrazine and guanidine and secondary aliphatic amines under
mild conditions in THF/H2O (1:1) afforded the corresponding N-alkyl and N,N-dialkyl 3-N-phenylthiocarbamoyl-
2-butenamides (2a-g and 2h-j) and 1,4-bis(3-N-phenylthiocarbamoyl-2-butenoyl)piperazine
(2k). In addition, the reaction of 1 with tertiary aromatic and aliphatic amines in the same conditions
led to stable 1,4-diionic nitrogen betaines 2l-n. These showed the nucleophilic attacks of primary and
secondary aliphatic amines, N,N′-dinucleophiles and tertiary aromatic and aliphatic amines on
thioesteric carboxyl group (C-2) of the thiophene-2,3-dione ring (1), due to the extremely high reactivity
of the thioesteric carboxyl group.
Conclusion: In conclusion, we have described a convenient route for the synthesis of 3-N-phenylthiocarbamoyl-
2-butenamide derivatives (2a-n) from 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-
dione (1) with primary and secondary aliphatic amines, N,N′-dinucleophiles and tertiary aromatic and
aliphatic amines in medium to good yields. The advantage of the present procedure is that the reaction
is performed in aqueous medium at room temperature by simple mixing of the starting materials.