A New Efficient Route to 2-Alkylsemicarbazides

Synthesis of hardly available 2-alkylsemicarbazides and their hydrochlorides from semicarbazide hydrochloride has been developed. This general and efficient protocol is based on preparation of acetone semicarbazone, its N2-alkylation in the presence of sodium hydride, and hydrolysis under mild conditions

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

A general stereoselective approach to previously unknown 1,2,4-triazepane-3-thiones/ones based on reduction or reductive alkylation of readily available 2,4,5,6-tetrahydro-3H-1,2,4-triazepine- 3-thiones/ones has been developed. The approach involved treatment of tetrahydrotriazepines with sodium cyanoborohydride in MeOH at pH 3 or with sodium borohydride and excess of carboxylic acid in tetrahydrofuran to give 1-unsubstituted or 1-alkyl-substituted 1,2,4-triazepane-3- thiones/ones, respectively. The latter were also prepared by reaction of 1-unsubstituted 1,2,4- triazepane-3-thiones/ones with sodium cyanoborohydride and aldehyde in MeOH in the presence of AcOH

An Unexpected Result of Base-Promoted Rearrangement of 4a-Acetyl-8a-hydroxydecahydroquinazoline-2-thione

Treatment of 4a-acetyl-8a-hydroxydecahydroquinazoline-2-thione with NaH in acetonitrile leads to its isomerization into 1-hydroxy-1-methyl-3-thioxo-2,4-diazaspiro[5.5]undecan-7-one followed by the C1-C6 bond cleavage to give N-acetyl-N’-[(2-oxocyclohexyl)methyl]thiourea. The starting compound as a single diastereomer was prepared by the reaction between the K-enolate of 2-acetylcyclohexanone and N-(tosylmethyl)thiourea or N-(azidomethyl)thiourea

An Unexpected Result of Base-Promoted Rearrangement of 4a-Acetyl-8a-hydroxydecahydroquinazoline-2-thione

Treatment of 4a-acetyl-8a-hydroxydecahydroquinazoline-2-thione with NaH in acetonitrile leads to its isomerization into 1-hydroxy-1-methyl-3-thioxo-2,4-diazaspiro[5.5]undecan-7-one followed by the C1-C6 bond cleavage to give N-acetyl-N’-[(2-oxocyclohexyl)methyl]thiourea. The starting compound as a single diastereomer was prepared by the reaction between the K-enolate of 2-acetylcyclohexanone and N-(tosylmethyl)thiourea or N-(azidomethyl)thiourea

A New Approach to 5-Functionalized 1,2-Dihydropyrimidin-2-ones/imines via Base-Induced Chloroform Elimination from 4-Trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones/imines

A novel four-step methodology for the synthesis of 5-acyl- and 5-arylsulfonyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]-ureas with Na-enolates of 1,3-diketones, β-oxoesters, or α-arylsulfonylketones followed by heterocyclization–dehydration of the oxoalkylureas formed gave 5-acyl- or 5-arylsulfonyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of strong bases, eliminates CHCl3 to give the target compounds. The above methodology was also used in the synthesis of 5-acyl-1,2-dihydropyrimidin-2-imines starting from N-[(1-acetoxy-2,2,2-trichloro)ethyl]-N′-guanidine

Synthesis of γ‑Azido-β-ureido Ketones and Their Transformation into Functionalized Pyrrolines and Pyrroles via Staudinger/aza-Wittig Reaction

A simple two-step procedure yielding γ-azido-β-ureido ketones or/and their cyclic isomers, 6-(1-azidoalkyl)-4-hydroxyhexahydropyrimidin-2-ones, has been developed. The synthesis includes three-component condensation of acetals of 2-azidoaldehydes with urea or methylurea and <i>p</i>-toluenesulfinic acid in aqueous formic acid followed by reaction of the obtained <i>N</i>-[(2-azido-1-tosyl)­alkyl]­ureas with sodium enolates of α-functionalized ketones. The azido ketones or their cyclic isomers are transformed into ureido-substituted Δ¹- or/and Δ²-pyrrolines via Staudinger/aza-Wittig reaction promoted by PPh₃. The obtained pyrrolines are converted into 3-functionalized 1<i>H</i>-pyrroles via elimination of urea under acidic conditions. Convenient one-pot syntheses of 1<i>H</i>-pyrroles starting from <i>N</i>-[(2-azido-1-tosyl)­alkyl]­ureas or γ-azido-β-ureido ketones have been also developed

Practical synthesis of β-isothiocyanato ketones from chalcones

<p>Practical synthesis of 1,3-diaryl-substituted 3-isothiocyanatopropan-1-ones based on the reaction of chalcones with thiocyanic acid generated in situ by treatment of thiocyanate ammonium with dilute sulfuric acid has been developed.</p

Nucleophile-Mediated Ring Expansion of 5‑Acyl-substituted 4‑Mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones in the Synthesis of 7‑Membered Analogues of Biginelli Compounds and Related Heterocycles

A general six-step approach to alkyl 2-oxo-2,3,6,7-tetrahydro-1<i>H</i>-1,3-diazepine-5-carboxylates and 5-acyl-2,3,6,7-tetrahydro-1<i>H</i>-1,3-diazepin-2-ones based on the nucleophile-mediated ring expansion reaction of 5-functionalized 4-mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones has been developed. Synthesis of the latter involved nucleophilic substitution of tosyl group in readily available <i>N</i>-[(2-benzoyloxy-1-tosyl)­ethyl]­urea with sodium enolates of β-oxoesters or 1,3-diketones, followed by dehydration or heterocyclization-dehydration of resulting products, removal of benzoyl protection, and conversion of hydroxymethyl group into mesyloxymethyl group. Conformations of the obtained tetrahydro-1<i>H</i>-1,3-diazepin-2-ones in solid state and solutions were established using X-ray diffraction and NMR spectroscopy. A plausible mechanism of tetrahydropyrimidine ring expansion based on DFT calculation at B3LYP/6-31+G­(d,p) level and NMR monitoring experiments was discussed. The ring contraction reaction of methoxy- or phenylthio-diazepinones under acidic conditions resulted in the corresponding 3-functionalized 1-carbamoyl-1<i>H</i>-pyrroles

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

Unprecedented self-assembly of a novel 14-membered cyclic bis-thiosemicarbazone or/and a 28-membered cyclic tetrakis-thiosemicarbazone upon acid-promoted cyclooligomerization of 4-(4-thiosemicarbazido)butan-2-one hydrazone has been discovered. A thorough study of the influence of various factors on the direction of macrocyclization provided the optimal conditions for the highly selective formation of each of the macrocycles in excellent yields. Plausible pathways for macrocyclizations have been discussed. The macrocycle precursor was prepared by the reaction of readily available 4-isothiocyanatobutan-2-one with an excess of hydrazine