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Synthesis of amides
Synthesis of protected primary amines

Ritter Reaction

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.

Recent Literature

Fe(ClO4)3ĚH2O-Catalyzed Ritter Reaction: A Convenient Synthesis of Amides from Esters and Nitriles
C. Feng, B. Yan, G. Yin, J. Chen, M. Ji, Synlett, 2018, 29, 2257-2264.

Polyoxometalate-Ionic Liquid-Catalyzed Ritter Reaction for Efficient Synthesis of Amides
L. Zhang, B. Chen, P. He, G. Li, L.-C. Zhang, S. Gao, Synlett, 2022, 33, 1515-1518.

An efficient method for the conversion of aromatic and aliphatic nitriles to the corresponding N-tert-butyl amides: a modified Ritter reaction
K. L. Reddy, Tetrahedron Lett., 2003, 44, 1453-1455.

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.

Synthesis of N-Benzhydrylamides from Nitriles by Ritter Reactions in Formic Acid
G. C. Gullickson, D. E. Lewis, Synthesis, 2003, 681-684.

One-Pot Synthesis of Isocyanides from Alcohols
I. Okada, Y. Kitano, Synthesis, 2011, 3997-4002.

Iron-Catalyzed Carboamination of Olefins: Synthesis of Amines and Disubstituted β-Amino Acids
B. Qian, S. Chen, T. Wang, X. Zhang, H. Bao, J. Am. Chem. Soc., 2017, 139, 13076-13082.

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.

Regioselective Three-Component Synthesis of Vicinal Diamines via 1,2-Diamination of Styrenes
J. Cao, D. Lv, F. Yu, M.-F. Chiou, Y. Li, H. Bao, Org. Lett., 2021, 23, 3184-3189.

γ-Amino Butyric Acid (GABA) Synthesis Enabled by Copper-Catalyzed Carboamination of Alkenes
N. Zhu, T. Wang, L. Ge, Y. Li, X. Zhang, H. Bao, Org. Lett., 2017, 19, 4718-4721.

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.

NaI-Mediated Acetamidosulfenylation of Alkenes with Bunte Salts as Thiolating Reagent Leading to β-Acetamido Sulfides
R. Zhang, Z. Yan, D. Wang, Y. Wang, S. Lin, Synlett, 2017, 28, 1195-1200.

A CAN-Induced Cyclodimerization-Ritter Trapping Strategy for the One-Pot Synthesis of 1-Amino-4-aryltetralins from Styrenes
V. Nair, R. Rajan, N. P. Rath, Org. Lett., 2002, 4, 1575-1577.