Hengyuan Lang

Novel and convenient routes to substituted pyrroles and imidazoles

Abstract S-Melhyl N-(benzotriazol-1-ylmethyl)thioimidate 6 is obtained by lithiation of the corresponding N-(benzotriazol-1-ylmelhyl) thioamide 5 and subsequent reaction with methyl iodide. Derivative 6 undergoes [2 + 3] cycloaddition reactions with α,β-unsaturated -esters, -ketones and -nitriles, and vinylpyridines which are followed by elimination of benzotriazole and the thioalkoxy group, to give 2,3,4-trisubstituted pyrroles. Lithiaiion of 6 followed by reactions with imines gives cyclized 4,5-dihydroimidazoles 14 which upon further treatment with ZnBr2 or direct refluxing in toluene yield the 1,25-trisubstituted imidazoles 15 in good yields.

A new route to N-substituted heterocycles

Abstract N-(Benzotriazol-1-ylmethyl)-indole, - pyrrole, -carbazole, and -benzimidazole, and analogs substituted in the methylene group are converted by lithium aluminum hydride, or by Grignard reagents, or in two cases by organozinc reagents, into the N-substituted heterocycles in good yields.

Benzotriazolylmethylaminosilanes: Novel azomethine ylide equivalents

Abstract Benzotriazolylmethylaminosilanes, readily accessible from the reaction of benzotriazole, an aldehyde and an (aminomethyl)silane in water at 20°C, are azomethine ylide equivalents which undergo stereospecific cycloadditions with dipolarophiles to give substituted pyrrolidines or 2,5-dihydropyrroles in good yields.

Novel routes to 4-substituted N,N-dialkylanilines, N-alkylanilines and anilines

Abstract 4-(Benzotriazol-1-ylmethyl)-N,N-dialkylanilines, -N-alkylanilines, -anilines and some substituted analogs obtained via lithiation are converted by lithium aluminum hydride or Grignard reagents into 4-substituted N,N-dialkylanilines, N-alkylanilines and anilines, respectively, in good yields.

Synthetic Elaboration of N-Substituents in Thioamides

Abstract N -(Benzotriazol-1-ylmethyl)arylthioamides, readily prepared from arylthioamides, formaldehyde and benzotriazole, undergo lithiation followed by reactions with alkyl halides, aldehydes and ketones to introduce the expected N -substituents into the N -methylene group. Subsequent displacements of the benzotriazolyl group by Grignard reagents, alkoxide or thioalkoxide anions provide general access to a wide variety of N -substituted thioamides in good yields.

A Novel Route to N-Styrylamides

Abstract A general synthesis of N-styrylamides starting from amides and phenylacetaldehyde is described. Condensation of the amide, aldehyde and benzotriazole affords N-(1-benzotriazol-l-yl-2-phenylethyl)amides 2 from which the benzotriazole molecule is smoothly eliminated.

A novel and convenient route to (1H-1,2,4-triazol-1-ylmethyl)phenols, anilines, N-alkylanilines and N,N-dialkylanilines

Phenols, naphthols, anilines, N-alkylanilines and N,N-dialkylanilines are readily alkylated by 1-hydroxymethyl- 1,2,4-triazole to afford the corresponding triazole derivatives in good yields

A Novel and Convenient Preparation of 1-(γ-Aminoalkyl)-Substituted 1,2,4-Triazoles

Abstract 1-(α-Aminomethyl)-1,2,4-triazoles readily add to enol ethers or enamides to give novel classes of compounds, 1-(γ-amino-α-alkoxy)propyl- (8) and 1-(γ-amino-α-amido)propyl- (10) substituted 1,2,4-triazoles, in excellent yields.

Benzotriazole stabilized lithium intermediates as a route to the elaboration of N-substituents in amides

Abstract Lithiation of N-(benzotriazol-1-ylmethyl)benzamide or N-(benzotriazol-1-ylmethyl)-2,2-dimethylbutyramide, readily prepared from the corresponding amides, formaldehyde and benzotriazole, followed by quenching with various electrophiles, such as alkyl halides, ketones or ester, gives the corresponding N-substituted derivatives. Subsequent displacement of the benzotriazole group with Grignard reagents, thiols or alcohols provides access to a wide variety of N-substituted amides in good yields. Treatment of the N-(benzotriazol-1-ylalkyl)benzamides with n- BuLi afforded the 1,1-dibenzamidoalkanes.

AN UNEXPECTED FORMATION OF DIETHYL TRANS-2,3- PIPERAZINEDICARBOXYLATES

Heating N-(benzotriazol-l-yl)glycine ethyl esters 2, obtained by Mannich condensation of glycine ethyl esters 1, formaldehyde and benzotriazole, in THF in the presence of excess of NaH unexpectedly gave diethyl fra/w-2,3-piperazinedicarboxylates 2. Work in our group has demonstrated the versatility of benzotriazole as a synthetic auxiliary in organic synthesis (1-4). The benzotriazole anion is a good leaving group and can be used in place of a halogen or other substituents in many transformations. In particular, we found that the benzotriazole group in Mannich adducts (RlR^NCHRBt), readily prepared from condensation of a secondary amine, an aldehyde and benzotriazole, can be easily displaced by carbanions from RMgBr and RLi or reduced by NaBH4 under mild conditions to give tertiary amines (5-7). These convenient intermolecular substitutions prompted us to investigate the possibility of intramolecular substitution utilizing benzotriazole as a leaving group to synthesize cyclic compounds.