A two-step synthesis of 1,5-disubstituted tetrazoles containing a siloxy or sulfonamide group

A simple two-step route to the synthesis of 1,5-disubstituted tetrazoles containing a β-siloxy or β-sulfonamide group is presented. The synthesis takes place via an isocyanide-based multicomponent reaction and allows incorporation of a wide variety of substitution patterns starting from commercially available reagents. This is followed by cyclization of the ketenimines with trimethylsilyl azide without using any catalyst or activation.     

New methods for the synthesis of amides of benzo[b]thiophene-2carboxylic acid

The reaction of 3-bromothiocoumarin with nitrogen bases, during which the thiocoumarin system is converted to a benzothiophene system, was studied. A new method for the synthesis of amides of benzo[b]thiophene-2-carboxylic acid is proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1340–1342, October, 1978.     

Triphenyl borate catalyzed synthesis of amides from carboxylic acids and amines

Herein we report triphenyl borate as a new catalyst for synthesis of amides by catalytic condensation of carboxylic acids and amines. Our protocol is applicable for synthesis of wide range of amides furnishing excellent yields up to 92%. In addition developed method requires low catalyst loading, short time, less amount of solvent, works under air atmosphere and notably no need of azeotropic reflux using special Dean Stark apparatus or molecular sieves.     

Synthesis of 1-substituted tetrazoles via the acid-catalyzed [3+2] cycloaddition between isocyanides and trimethylsilyl azide

1-Substituted tetrazoles were synthesized via the [3+2] cycloaddition between isocyanides and trimethylsilyl azide in the presence of an acid catalyst and MeOH. Various 1-substituted tetrazoles were obtained in good to high yields. The reaction probably proceeds through the in situ formation of hydrazoic acid, followed by a successive [3+2] cycloaddition with the isocyanide activated by an acid.     

Direct synthesis of esters and amides from unprotected hydroxyaromatic and -aliphatic carboxylic acids

A facile method for the activation of hydroxy-substituted carboxylic acids using benzotriazole chemistry without prior protection of the hydroxy substituents is presented. The N-acylbenzotriazole intermediates 2a-g, 6a-d, and 9a-c have been used for high-yielding synthesis of both aliphatic (3a-l) and aromatic (7a-h, 10a-f) hydroxy carboxamides. High yields of aromatic hydroxy esters 12a-h and 13a-i were obtained using either neat alcohols in neutral microwave conditions or nucleophilic alkoxides and the intermediate N-(arylacyl)benzotriazoles. Moderate yields were obtained in the case of aliphatic hydroxy esters 11a,b and thiolesters 11e-g from the intermediates 2a-c.     

Condensation of n-alkyl-n-methylolamides of diethyl phosphoric acid with carboxylic acid amides

Conclusions Condensation of the N-alkyl-N-methylolamides of diethyl phosphoric acid (alkyls - methyl, ethyl, propyl, butyl, and amyl) with amides of formic, acetic, and chloroacetic acids and urethane gave the corresponding N-alkyl-N-(acylaminomethyl)amides of diethyl phosphoric acid; the products have been characterized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2133–2134, September, 1968.     

A novel system for the synthesis of nitriles from carboxylic acids

A simple, mild and high yielding method for the conversion of various carboxylic acids to nitriles has been developed using diphosphorus tetraiodide in combination with ammonium carbonate at room temperature.     

Selective synthesis of ureas and tetrazoles from amides controlled by experimental conditions using conventional and microwave irradiation

An efficient synthetic procedure has been achieved for selective synthesis of 1,5-disubstituted tetrazoles and diaryl ureas from secondary amides in situ in the presence of NaN₃ and POCl₃ as solvent, both by conventional and microwave methods. The reaction conditions were optimized to yield selectively either tetrazoles or urea derivatives from reasonable to excellent yields. These conversions have been tested and verified with various secondary amide precursors. The synthesized compounds were characterized by ¹H NMR, ¹³C NMR and ESI-MS spectroscopic techniques.     

A novel synthesis of 1-aryl tetrazoles promoted by employing the synergy of the combined use of DMSO and an ionic liquid as the solvent system at ambient temperature

The synergy of the combined use of DMSO and an ionic liquid viz. (bbim)⁺Br⁻ has brought about a mild, convenient, efficient, and rapid protocol for the synthesis of 1-substituted-1H-1,2,3,4-tetrazoles via the condensation of amines, triethyl orthoformate, and sodium azide at ambient temperature in excellent isolated yields (85-90%). The inherent Bronsted acidity of ionic liquid and high polarity of both IL and DMSO resulted in a significant enhancement in the reaction rate.     

One pot direct synthesis of amides or oxazolines from carboxylic acids using Deoxo-Fluor reagent

A mild and highly efficient one pot-one step condensation and/or condensation-cyclization of various acids to amides and/or oxazolines using Deoxo-Fluor reagents is described. Parallel syntheses of various free fatty acids with 2-amino-2,2-dimethyl-1-propanol resulted with excellent yields.     

New cleavable isocyanides for the combinatorial synthesis of α-amino acid analogue tetrazoles

3-Substituted 3-isocyano propionates as new cleavable isocyanides in combinatorial tetrazole synthesis via Ugi-reaction are introduced. The obtained 5-substituted tetrazoles are transformed into carboxylic acid isosteric 5-substituted 1H-tetrazoles under basic cleavage conditions.     

A one-flask synthesis of Weinreb amides from chiral and achiral carboxylic acids using the deoxo-fluor fluorinating reagent

[structure] The reagent [bis(2-methoxyethyl)amino]sulfur trifluoride (Deoxo-Fluor reagent) converts carboxylic acids to the corresponding acid fluorides, which then react with N,N-dimethylhydroxylamine to give the corresponding Weinreb amides in high yields. The reaction proceeds without racemization when optically active acids are used as the starting material. This method is operationally simple and provides the products in high purity.     

Carbamoylimidazolium salts as diversification reagents: an application to the synthesis of tertiary amides from carboxylic acids

An efficient method for the preparation of tertiary amides from carbamoylimidazolium salts and carboxylic acids is described. The transformation occurs at room temperature and under relatively mild conditions. The carbamoylimidazolium salts are obtained from the reaction of secondary amines with N,N′-carbonyldiimidazole, followed by methylation with methyl iodide. The utility of this reaction was demonstrated in the formation of Weinreb amides and in a short synthesis of fused bicyclic amides. The introduction of this reaction now permits carbamoylimidazolium salts to be utilized in the formation of tertiary amides, ureas, carbamates and thiocarbamates under a single set of conditions.     

Use of phosphite amides in the synthesis of polyamides

The preparation of polyamides by the phosphite amide procedure was investigated. The yield of amidation was determined in the reaction of diethyl- or o-phenylenephosphite derivatives of piperidine, piperazine, or trans-2,5-dimethylpiperazine with either mono- or dicarboxylic acids. Higher yields were obtained by using diethyl phosphite derivatives; however, for both types of derivatives the yields were never greater than 90%. Only low molecular weight polymers could be obtained under optimum reaction conditions. In the polycondensation of (+)-trans-1,3-cyclohexanedicarboxylic acid or (+)-trans-1,2-cyclohexanedicarboxylic acid with phosphite derivatives of either piperazine or trans-2,5-dimethylpiperazine, the optical rotation of the polymers was lower than the rotation of the corresponding polyamides prepared by the interfacial condensation procedure with dicarboxylic acid chlorides. It was shown that an intermediate mixed anhydride was formed during the amidation reaction. This may account for the observed racemization.     

Protease catalysis mediated by a substrate mimetic: a novel enzymatic approach to the synthesis of carboxylic acid amides

We present a protease-based method for the coupling of non-coded and non-amino-acid-derived amines with carboxy components. The key feature of this approach is the combination of the substrate-mimetic strategy with the ability of the cysteine protease clostripain to accept a wide spectrum of amines. Firstly, we tested the use of the 4-guanidinophenyl ester leaving group to mediate acceptance of non-coded and non-amino-acid-derived acyl residues. This employed beta-amino acid and simple carboxylic acid moieties as acyl donors, and several amino acid and peptide units as acyl acceptors. The study was completed by the use of non-amino-acid-derived acyl acceptors comprising simple amines, amino alcohols, and diamines. The results indicate that the approach presented is a useful strategy for the synthesis of peptide isosteres, peptide analogues, and organic amides. These last open a new range of synthetic applications of proteases completely beyond peptide synthesis, achieving efficient and selective acylations of non-amino-acid-derived amines under extraordinarily mild reaction conditions.     

Mechanochemical synthesis of primary amides from carboxylic acids using TCT/NH4SCN

A facile and effective approach toward the synthesis of primary amides from carboxylic acids has been developed. In the presence of 2,4,6-trichloro-1,3,5-triazine, a combination of ammonium thiocyanate and potassium carbonate led to the rapid conversion of carboxylic acids into the corresponding amides within five minutes grinding at room temperature. The use of ammonium thiocyanate as the amine source is unprecedented and exclusive formation of primary amides is observed only under the liquid-assisted grinding conditions.