Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

In the presence of catalytic amount of bismuth bromide (5 mol %) the α-amido p-tolylsulfones are converted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to provide the N-protected α-amino nitriles in very good yield. A variety of α-amido p-tolylsulfones were prepared from aromatic as well as aliphatic aldehydes for the synthesis of α-amino nitriles.     

Facile transformation of esters to nitriles

Various esters were efficiently converted into the corresponding nitriles in good yields by the treatment with sodium diisobutyl-tert-butoxyaluminium hydride (SDBBA-H), followed by treatment with molecular iodine in aq ammonia. The present one-pot method is very efficient and practical for the conversion of various aromatic and aliphatic esters into the corresponding nitriles.     

One-pot conversion of aromatic bromides and aromatics into aromatic nitriles via aryllithiums and their DMF adduct

Various aromatic bromides and iodides were smoothly converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃. The same treatment of typical aromatics and heteroaromatics with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH₃ also provided the corresponding aromatic nitriles in good yields. Moreover, the same treatment of aromatic bromides and aromatics with half amount of DIH (1,3-diiodo-5,5-dimethylhydantoin) instead of molecular iodine worked effectively to give the corresponding aromatic nitriles, respectively, in good yields. These reactions are novel and environmentally benign one-pot methods for the preparation of aromatic nitriles from aromatic bromides and aromatics, respectively, through the formation of aryllithiums and their DMF adducts.     

An efficient method for the conversion of aromatic and aliphatic nitriles to the corresponding N-tert-butyl amides: a modified Ritter reaction

Aromatic and aliphatic nitriles react with tert-butyl acetate in the presence of a catalytic amount of sulfuric acid to give the corresponding N-tert-butyl amides in excellent yields.     

A simple one-pot procedure for the direct conversion of alcohols into alkyl nitriles using TsIm

A convenient and efficient one-pot preparation of nitriles from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, treatment of alcohols with a mixture of NaCN, TsIm and triethylamine in the presence of catalytic amounts of tetra-n-butylammonium iodide (TBAI) in refluxing DMF furnishes the corresponding alkyl nitriles in good yields. This methodology is highly efficient for various structurally diverse alcohols with selectivity for ROH: 1° > 2° > 3°.     

Aminoalkylation of nitriles by iminium ions generated in situ

Aminoalkylation of a series of primary and secondary nitriles with N-(α-aminoalkyl)benzotriazoles 1 (derived from a variety of secondary amines and aldehydes) proceeds smoothly providing the corresponding β-aminoalkyl nitriles 5a-j in 66-97% yields.     

Copper-catalyzed synthesis of 5-substituted 1H-tetrazoles via the [3+2] cycloaddition of nitriles and trimethylsilyl azide

The [3+2] cycloaddition between various nitriles and trimethylsilyl azide proceeds smoothly in the presence of a Cu^I catalyst in DMF/MeOH, to give the corresponding 5-substituted 1H-tetrazoles in good to high yields. The reaction most probably proceeds through the in situ formation of a copper azide species, followed by a successive [3+2] cycloaddition with the nitriles.     

Silica-bonded S-sulfonic acid: an efficient and recyclable solid acid catalyst for the three-component synthesis of α-amino nitriles

Silica-bonded S-sulfonic acid (SBSSA) is employed as a recyclable catalyst for the synthesis of α-amino nitriles. These syntheses were performed via a one-pot three-component condensation of aldehydes, amines, and trimethylsilyl cyanide under mild reaction conditions at room temperature.     

One-pot synthesis of aza-Morita-Baylis-Hillman adducts from α-oxo ketene-S,S-acetals, arylaldehydes and nitriles

Promoted by TiCl₄, a series of α-(1,3-dithiolan-2-ylidene)-β-amino carbonyl derivatives--the aza-Morita-Baylis-Hillman adducts, have been synthesized from α-oxo cyclic ketene-S,S-acetals, arylaldehydes, and nitriles in good to excellent yields. A mechanism involving sequential Morita-Baylis-Hillman and Ritter reactions for this novel one-pot, three-component reaction is described.     

Sodium bromide catalysed one-pot synthesis of tetrahydrobenzo[b]pyrans via a three-component cyclocondensation under microwave irradiation and solvent free conditions

Sodium bromide catalysed three-component cyclocondensation of aryl aldehydes, alkyl nitriles and dimedone proceeds under microwave irradiation in solvent free conditions to give highly functionalised tetrahydrobenzo[b]pyrans in excellent yields.     

Highly selective substitutions in 2,3-dichloropyrazine. A novel general approach to aloisines

A highly efficient synthesis of the potent CDKs (cyclin-dependent kinases) inhibitors, aloisines (substituted 5H-pyrrolo[2,3-b]pyrazines) is presented. The method is based on highly selective monosubstitution of a single chlorine atom in 2,3-dichloropyrazine with lithiated ketones, esters, and nitriles followed by co-cyclization of the resulting intermediates with primary amines or hydrazines.     

Nano TiO2/SO4 as a heterogeneous solid acid catalyst for the synthesis of 5-substited-1H-tetrazoles

An efficient and economical protocol for the synthesis of 5-substituted-1H-tetrazoles from various nitriles and sodium azide is reported using nano TiO₂/SO₄²⁻ as an effective heterogeneous catalyst. A wide variety of aryl nitriles underwent [3 + 2] cycloaddition to afford tetrazoles in good to excellent yields.     

Eco-friendly synthesis of guanidinyltetrazole compounds and 5-substituted 1H-tetrazoles in water under microwave irradiation

We have developed simple, short time, cost effective, purification of products by non-chromatographic methods and environmentally benign protocol for the synthesis of guanidinyltetrazoles and 5-substituted 1H-tetrazoles derivatives via [2,3]cyclo-addition reaction of nitriles and azide derivatives in water under microwave irradiation. All the synthesized products are screened for their in vitro antimicrobial activity. The synthesized compounds were obtained in excellent yield (85–98%).     

Oxidative fragmentation of oxiranes to nitriles with hypervalent iodine(V) reagents in aqueous ammonia

Oxiranes undergo oxidative fragmentation when treated with hypervalent iodine(V) reagents particularly o-iodoxybenzoic acid in aqueous ammonia to give nitriles. The reaction goes via the formation of 1, 2-amino alcohols as intermediates followed by C-C bond cleavage.     

Synthesis and molecular structure of spirocyclic 2-oxindole derivatives of 2-amino-4H-pyran condensed with the pyrazolic nucleus

4,3′-Spiro[(6-amino-5-R-3-methyl-2H,4H-pyrano[2,3-c]pyrazolo)-2′-oxindoles] were synthesized based on the three-component condensation of isatins with 3-methyl-pyrazolone-5 and respective methylene active nitriles in the presence of basic catalysts. The molecular structure of the resulting compounds was proved unambiguously by X-ray diffraction.     

CuFe2O4 nanoparticles: a magnetically recoverable and reusable catalyst for the synthesis of 5-substituted 1H-tetrazoles

An efficient and economical protocol for the synthesis of 5-substituted 1H-tetrazoles from various nitriles and sodium azide is described using magnetically recoverable and reusable CuFe₂O₄ nanoparticles. A wide variety of aryl nitriles underwent [2+3] cycloaddition under mild reaction conditions to afford tetrazoles in good to excellent yields. The catalyst was magnetically separated and reused five times without significant loss of catalytic activity.     

An efficient,three-component synthesis and molecular structure of derivatives of 2-amino-3-R-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide spirocombined with a 2-oxindole nucleus

Spiro[(2-amino-3-R-6-ethyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazine-5,5-dioxide)-4,3′-(1′-R′-5′-R″-indolin-2′-one)] compounds were synthesized based on the three-component interaction of benzo[c][2,1]thiazin-4-on 2,2-dioxide with corresponding isatins and appropriate methylene active nitriles in the presence of a base as a catalyst. The molecular structures of the target compounds were proved uniquely by the X-ray diffraction analysis method.     

New fluorinated 1,3-vinylogous amidines as versatile intermediates: synthesis of fluorinated pyrimidin-2(1H)-ones

The condensation of the azaenolates derived from readily available ketimines with fluorinated nitriles offers an efficient and straightforward entry to new fluorinated 1,3-vinylogous amidines. These versatile compounds, in turn, react with triphosgene to yield new fluorinated pyrimidin-2(1H)-ones in high yields.     

A novel, one-pot, solvent-, and catalyst-free synthesis of 2-aryl/alkyl-4(3H)-quinazolinones

A novel and one-pot synthesis of 2-aryl/alkyl-4(3H)-quinazolinones is described. The in situ prepared amidoximes from the reaction between nitriles and hydroxylamine are condensed with anthranilic acids under solvent- and catalyst-free conditions to produce the title compounds in excellent yields.     

Synthesis of 5-substituted 1H-tetrazoles catalyzed by ceric ammonium nitrate supported HY-zeolite

In this Letter we wish to report a simple and efficient synthetic protocol for the synthesis of 5-substituted 1H-tetrazole derivatives through the [2+3] cycloaddition of nitriles with sodium azide using ceric ammonium nitrate supported HY-zeolite as a novel catalyst. Excellent yields of the corresponding tetrazoles were obtained through this cost-effective protocol under aerobic conditions with shorter reaction time under mild reaction conditions.