Thiocarbamate-Based Synthesis of 2,4,5,6-Tetrahydro-3H-1,2,4-Triazepine-3-Thiones

Abstract

A five-step synthesis of 5,7-diaryl-substituted 2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thiones starting from ethyl thiocarbamate was developed. The synthesis included a three-component condensation of ethyl thiocarbamate with aromatic aldehydes and p-toluenesulfinic acid to give O-ethyl[(aryl)(tosyl)methyl]thiocarbamates which were transformed into the corresponding O-ethyl (3-phenyl-3-oxopropyl) thiocarbamates by treatment with the sodium enolate of dibenzoylmethane followed by base-promoted retro-Claisen condensation. Reaction of the prepared thiocarbamates with hydrazine and subsequent acid-catalysed cyclisation of the derived 4-[(3-hydrazono-3-phenyl)prop-1-yl]semicarbazides gave the target triazepines.

Different Modes of Acid-Promoted Cyclooligomerization of 4-(4-Thiosemicarbazido)butan-2-one Hydrazone: 14-Membered versus 28-Membered Polyazamacrocycle Formation

“…We hypothesized that an alternative synthesis could involve acid-promoted cyclization of thioxo-analogues of hydrazones 1 (e.g., 5 , Scheme B). However, in contrast to the preparation of 1 from ethyl carbamate, the synthesis of their thioxo-analogues from ethyl thiocarbamate failed . Another approach to hydrazones of 4-(3-oxoprop-1-yl)­thiosemicarbazides could be based on the reaction of 4-isothiocyanatobutan-2-ones with hydrazine.…”

“…However, in contrast to the preparation of 1 from ethyl carbamate, 14b the synthesis of their thioxo-analogues from ethyl thiocarbamate failed. 20 Another approach to hydrazones of 4-(3-oxoprop-1-yl)thiosemicarbazides could be based on the reaction of 4-isothiocyanatobutan-2-ones with hydrazine. The initially formed products of this reaction, 4-(4-thiosemicarbazido)butan-2-ones, are known to cyclize spontaneously to the corresponding 3-amino-4-hydroxyhexahydropyrimidine-2-thiones.…”

Novel semicarbazone-based α-amidoalkylating reagents: general synthesis and reactions with <em>H</em>-, <em>O</em>-, <em>S</em>-, <em>N</em>-, and <em>P</em>-nucleophiles

“…Commonly, electrophilic amidoalkylating reagents are based on carboxamides and carbamates [1][2][3]. Their preparation from other amides, e.g., ureas [24][25][26][27], thioureas [28][29][30], guanidines [31][32][33], thio-and dithiocarbamates [34][35][36], amides of various oxoacids of sulfur [37,38] and phosphorus [39,40] has been much less studied. To the best of our knowledge, there are no reports on preparation and application of semicarbazide-based amidoalkylating reagents.…”

A General Stereoselective Approach to 1,2,4-Triazepane-3-thiones/ones via Reduction or Reductive Alkylation of 2,4,5,6-Tetrahydro-3H-1,2,4-triazepine-3-thiones/ones

“…The reported syntheses of 1,2,4-triazepin-3-ones/thiones include the reaction of β-isocyanato and β-isothiocyanato ketones with hydrazines [16][17][18][19][20][21][22][23][24], condensation of semicarbazides and thiosemicarbazides with various 1,3-dicarbonyl compounds or their derivatives [10,[25][26][27][28][29][30][31][32][33], reaction of arylidene ketones with N2H4•2HNCS [34], addition of semicarbazides and thiosemicarbazides to α,β-unsaturated carbonyl compounds or their synthetic equivalents [35][36][37][38][39], reaction of γ-hydrazinosubstituted amines with phosgene equivalents [8,[13][14][15]40], and intramolecular cyclization of 4-(γ-oxoalkyl)semicarbazides and 4-(γ-oxoalkyl)thiosemicarbazides or their derivatives [17,22,41,42]. Generally, these methods give access to 1,2,4-triazepin-2-ones/thiones with one or two double bonds in the 7-membered ring.…”