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The y-gauche effect or y-steric shift effect is referred to in this context for the synclinal arrangement of substituent and carbon atom which results in an upfield shift of that carbon relative to the shielding of a corresponding carbon in the antiperiplanar conformation.10 A recent report has cautioned the extrapolation of this generalization to complex systems since 1,3-syn axial substituents in sorne six-membered rings (e.g., steroids) exhibit appreciable downfield shifts (often referred to as d effects)."

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Receiued April 12, 1976 N-Ethoxycarbonylthioamides react with hydrazine or monosubstituted hydrazines to form 2,4-dihydro-3H-1,2,4-triazol-3-ones (4-7), and with 1,2-dimethylhydrazine to form 1,2-dimethyl-1,2-dihydro-3H-1,2,4-triazol-3-ones (8). Analogous reactions with hydroxylamine or N-methylhydroxylamine yield 1,2,4-oxadiazol-5(4H)-ones (9) or 2-methyl-1,2,4-oxadiazol-5(2H)-ones (lo), respectively.Through their condensation-cyclization reactions, alkoxycarbonyl isothiocyanates have proved valuable synthetic tools in heterocyclic chemistry.1 The carbamates resulting from addition of alcohols or amines to ethoxycarbonyl isothiocyanate2 and their S-methyl derivatives3 have been found to undergo cyclization reactions with difunctional nucleophilic reagents. However, analogous reactions of the somewhat less easily accessible N-ethoxycarbonylthioamides (1) have not attracted attention. Treatment of 1 with primary or secondary amines results in elimination of H2S and formation of N'-ethoxycarbonylamidines (2).4 These compounds may be expected to undergo cyclization with loss of EtOH, if the amine used as reagent contains a suitably located, second nucleophilic group YH. The present paper describes such reactions of 1 leading to heterocycles 3 with 1,2,4-triazole and 1,2,4-oxadiazole ring systems.Treatment of an N-ethoxycarbonylthioamide (1) with hydrazine or a monosubstituted hydrazine causes evolution of H2S and formation of a 2,4-dihydro-3H-1,2,4-triazol-3-one (4-7) in good to excellent yield (Tables I-IV). An analogous reaction with 1,2-dimethylhydrazine yields 1,2-dimethyl-1,2-dihydro-3H-1,2,4-triazol-3-ones (8) in moderate to good yields (Table V). Aqueous sodium hydroxide hydrolyzes carbamoyl derivatives 7 readily to the corresponding 4.There is considerable confusion in the literature concerning the location of the double bond in the dihydrotriazolone ring of compounds 4-6. Some authors place it between positions 1 and 5, others between positions 4 and 5.5 Structure 4 for the dihydro-1,2,4-triazolones obtained in this study is supported by appearance of the carbonyl band in their ir spectra at a considerably higher wavenumber (1700-1760 cm-l) than for dimethyl derivatives 8 (1655-1660 cm-l), in which the carbonyl group has to be conjugated with the double bond. With regard to monomethyl derivatives 5, no firm conclusion can be drawn on the basis of the carbonyl band (1670-1690 cm-l). However, the proposed structure is consistent with the close similarity between the uv spectra of 4 (maximum at 265-270 nm) and 5 (maximum a t 270-275 nm) and their significant difference from those of the corresponding 8 (maximum at 235-260, shoulder at 275-280 nm). The possibility that derivatives 5 are l-methyl-1,2-dihydro-3H-1,2,4-triazol-3-ones may be excluded, since compounds of such structure are known to exist in the enol form as 3-hydroxy-1,2,4-triazoles. Furthermore, the melting point (216.5-218.5 "C) of the product of the reaction of N-ethoxycarbonylthiobenzamide with methylhydrazine agrees well with that of 2-methy...

N-Benzoylthioamides (1) react with hydrazines and hydroxylamine to form lH-l,2,4triazoIes and 1,2,4-oxadiazoles, respectively. A similar treatment of the S-methyl derivatives of 1 with amidines leads to 1,3,5-triazines. Ethyl N-benzoylthiocarbamate undergoes analogous reactions to yield the corresponding e thoxyheterocycles. j . Heterocyclic Chern., 18, 1197 (1981).The reactions of N-ethoxycarbonylthioamides with hydrazines, hydroxylamines, and amidines involve nucleophilic attack at both thiocarbonyl and carbonyl groups and proceed with loss of hydrogen sulfide and ethanol to form substituted 1,2,4triazolones, 1,2,4oxadiazolones, and 1,3,5-triazinones, respectively (1,2). Analogous reactions of N-acylthioamides can be expected to result in loss of hydrogen sulfide and water and to yield the corresponding aromatic triazoles, oxadiazoles, and triazines in a straightforward manner. Surprisingly, very few examples of such reactions can be found in the literature. Thus, treatment of ethyl N-benzoylthiocarbamate with phenylhydrazine has been reported to lead to 3-ethoxy-l,5-diphenyl-lH-l,2,4triazole (3). More recently, the reaction of N-acetylthiobenzamide with phenylhydrazine was found to yield 5-methyl-1,3-diphenyl-lH-l,2,4triazole (4). N-Acylthioamides have been prepared by the Friedel-Crafts reaction between toluene and benzoyl isothiocyanate (5), by acylation of thioamides (4), and by lowtemperature treatment of acyl isothiocyanates with Grignard reagents (6). In our hands, the Friedel-Crafts method gave unsatisfactory yields (5-10% of purified product), but the low temperature reactions of benzoyl isothiocyanate with arylmagnesium bromides allowed the preparation of N-benzoylthioamides in reasonable yields (la, 48%; lb, 48%; lc, 35%).We have found that N-benzoylthioamides (la-c) react readily with hydrazine to form 3,5-diaryl-lH-l,2,4triazoles (2a-c) in very good yields. The structures assigned to these products are supported by spectral data (ir, nmr), as well as by the previously reported melting points for, the known 2a and 2b. Analogous reactions of la-c with methylhydrazine, benzylhydrazine, and phenylhydrazine lead to the corresponding 1,3,5-trisubstituted lH-1,2,4 triazoles (3a-c, 4a-c, and 5a-c) in generally good yield.However, for such monosubstituted hydrazines, the possibility exists that reaction with 1 may occur in either of two orientations to yield either triazoles 3-5, or their isomers 6, or both. The proposed product structure (3-5) assumes attack on the thiocarbonyl of 1 by the primary amino group of the monosubstituted hydrazines and is supported by the following observations. (a) Treatment of 1197 II II SO-s R = Me Ph/C\NH/C\ 4 0 -6 R = PhCH2 So-d R = Ph l a Y = Ph I b Y 4-CH3CgHq Ic Y = 4-i-PrC6H4 I d Y = EtO / \ 1.Y = E12N 3) R-CbNH 'NH2 N A ' N P h k N A R l o -d , f R = Ph Of Y I M e N-benzoyl-4isopropylthiobenzamide (lc) with aniline results in evolution of hydrogen sulfide and formation of N-benzoyl-N'-phenyl-4isopropylbenzamidine (9). (b) As mentioned earlier, N-acetylthiobenzamide is ...