The acid-induced nucleophilic addition of a nitrile to a carbenium ion, followed by hydrolysis to the corresponding amide.
Mechanism of the Ritter Reaction
Any substrate capable of generating a stable carbenium ion is a suitable starting material; primary alcohols do not react under these conditions, with exception of benzylic alcohols:
The carbenium ion adds to the nitrile nitrogen to give a nitrilium ion intermediate, which undergoes hydrolysis to the corresponding amide upon aqueous work-up.
Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination Leading to the Production of α-Tertiary Amine Derivatives
K. Kiyokawa, T. Watanabe, L. Fra, T. Kojima, S. Minakata, J. Org. Chem., 2017, 82, 11711-11720.
A regioselective electrochemical Ritter-type reaction at the C(sp2)-H of unprotected phenol enables an environmentally benign and direct synthesis of paracetamol. The reaction proceeds under exogenous oxidant- and catalyst-free conditions. The protocol is scalable and can be deployed to a variety of phenols.
I. M. Taily, D. Saha, P. Banerjee, Org. Lett., 2022, 24, 2310-2314.
A direct difunctionalization protocol of alkenes with nitriles and thiols under metal-free synthesis conditions provides various β-acetamido sulfides with very good yields simply by using inexpensive molecular iodine as a catalyst, DMSO as a mild oxidant, and readily available thiols as thiolating reagents.
H. Cui, X. Liu, W. Wei, D. Yang, C. He, T. Zhang, H. Wang, J. Org. Chem., 2016, 81, 2252-2260.
Molecular Iodine-Mediated Difunctionalization of Alkenes with Nitriles and Thiols Leading to β-Acetamido Sulfides
Y. Zheng, Y. He, G. Rong, X. Zhang, Y. Wang, K. Dong, X. Xu, J. Mao, Org. Lett., 2015, 17, 5444-5447.