Strecker Synthesis of α-aminonitriles Facilitated by N-methyl Imidazolium Acetate

N-Methyl imidazolium acetate [HMIm]OAc was simply prepared through reaction of N-methyl imidazole with acetic acid and it was applied as a media and promoter for Strecker synthesis of α-aminonitriles. The three component reaction of a variety of structurally different aldehydes and amines with trimethylsilyl cyanide (TMSCN) in the presence of [HMIm]OAc were evaluated. Reaction of aromatic aldehydes and cinnamaldehyde with either aromatic and aliphatic amines provided the corresponding α-aminonitriles in high to excellent isolated yields after short period of time at room temperature.

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

This work describes an efficient, simple, and ecofriendly sonochemical procedure for the preparation of new α-(arylamino)acetonitrile derivatives C-substituted with phenothiazine or ferrocene units. The synthetic protocol is based on the Strecker reaction of a (hetero)aryl aldimine substrate with trimethylsilyl cyanide (TMSCN) in poly(ethylene glycol) (PEG) solution. The advantages of the sonochemical versus the conventional α-(arylamino)acetonitrile synthesis are the significantly shorter reaction time (30 min instead of 72 hours), the higher purity and the easier separation of the product that precipitated from the reaction mixture in crystalline form as depicted by scanning electron microscopy (SEM) analysis. The single crystal X-ray diffraction analysis disclosed the arrangement of the α-(arylamino)acetonitrile molecules in the aggregated crystalline state as a racemic mixture. The mutagenic/antimutagenic potential for three representative derivatives containing phenothiazinyl, ferrocenyl, and phenyl units, respectively, was evaluated by the Ames Salmonella/microsome test using S. typhimurium TA98 and TA100 strains with and without metabolic activation. The preliminary screening results pointed out that the C-(hetero)aryl-α-(arylamino)acetonitrile derivatives can be considered genotoxically safe and possibly antimutagenic.

Absolute asymmetric Strecker synthesis in a mixed aqueous medium: reliable access to enantioenriched α-aminonitrile

Under aqueous conditions, total spontaneous resolution of α-aminonitrile occurred by the reaction of three achiral reagents; therefore, absolute asymmetric Strecker synthesis was demonstrated.