Acetonitrile as a Building Block and Reactant

Abstract

Acetonitrile is popular as a solvent for performing organic reactions, as a ligand in inorganic chemistry, as a mobile phase in chromatography, and as an electrolyte solvent in dye-sensitized solar cells. This is mainly due to its ability to dissolve both polar and nonpolar components. However, acetonitrile is also a valuable building block allowing atom-efficient transformations in synthetic organic chemistry. The aim of this review is to highlight synthetic transformations using acetonitrile, covering both classical approaches and modern strategies proceeding through radical intermediates or mediated by metal catalysis. Besides showcasing synthetic protocols useful for acetonitrile and analogues, warnings for when not to use acetonitrile as a solvent are also provided.1 Introduction2 Fundamental Reactions with Acetonitrile3 Cyanomethylation of Non-Aromatics4 The Acetonitrile Nitrogen as a Nucleophile5 The Blaise Reaction6 Synthesis of Pyridines7 Other Cyclization Reactions8 Cyanomethylation of Arenes and Heteroarenes9 Acetylation of Arenes Using Acetonitrile10 Synthesis of N-Arylacetamides11 Cyanation Using Acetonitrile as a Cyanide Source12 When To Avoid Acetonitrile as a Solvent13 Conclusion

Impurity Dimethylcarbamoyl-OBt Detected in an API Induced by the Degradation of HBTU in DMF

“…Apparently, the formation of dimethylcarbamoyl-OBt from HBTU degradation in NMP and ACN could not proceed through the mechanism proposed in Scheme , which should be unique to DMF. Despite such structural disparity, the underlying driving force for the formation of dimethylcarbamoyl-OBt in NMP and ACN could also be attributed to their intrinsic characteristic as an aprotic solvent with weak nucleophilicity . The mechanism is postulated in Scheme .…”

“…Despite such structural disparity, the underlying driving force for the formation of dimethylcarbamoyl-OBt in NMP and ACN could also be attributed to their intrinsic characteristic as an aprotic solvent with weak nucleophilicity. 6 The mechanism is postulated in Scheme 3.…”

Reaction Medium as the Installing Reservoir for Key Functionalities in the Molecules

“…The use of acetonitrile as a building block for the various transformations is recently compiled by Peng and cowokers (2016), Yan et al . (2017), Hoff (2018) and Nauth and Opatz (2019) . Although, we are not exploring the detailed compilation to restrict the duplicity, however, herein, we have covered the mechanistic aspects of the major cyanation and cyanomethylation reactions using ACN as a source which were not covered under earlier reports.…”

Transition-metal-catalyst-free reaction of amides and acetonitriles: synthesis of β-ketonitriles

“…It was known that acetonitrile is a very useful building block. 34 Herein, we report the transition-metal-free reaction between acetonitrile and both activated and unactivated amides to yield the corresponding β-ketonitriles (Scheme 1C).…”