Ritter reaction mechanism

Gerasimova, N. P., Nozhnin, N. A., Ermolaeva, V. V., Ovchinnikova, A. V., Moskvichev, Y. A., Alov, E. M., Danilova, A. S. The Ritter reaction mechanism New corroboration in the synthesis of arylsulfonyl(thio)propionic acid N-(1-adamantyl)amides. Mendeteev Commun. 2003, 82-84. 

The Ritter reaction [6] proceeds by the electrooxidation of alkyl iodides (56) in an MeCN-(Pt) system to form Ai-alkyl acetamides (58) (Scheme 21). Attack of carbenium ion intermediate - from dissociation of the initially formed alkyl cation radical - to acetonitrile would give the iminium cation (57). However, a different mechanism is proposed, whereby the alkyl iodide reacts with the electrogenerated iodo cation [I]" " [73]. 

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

Another collection of related intermediates occurs in the Ritter reaction and the Beckmann fragmentation. The Ritter reaction involves the combination of a tertiary alcohol and a nitrile in acid solution and the proposed mechanism involves a series of intermediates. 

It was suggested73 that the most probable mechanism of this reaction is an initial aldol condensation of the starting ketone leading to the a,/ -unsaturated ketone 100 or to the /Miydroxyketone 101 which serve as precursors to the tertiary carbenium ions 102, which reacts in turn with nitriles by an acid-catalyzed Ritter reaction to give 103 (equation 36). This suggestion is confirmed by the results of a cross-reaction experiment of benzaldehyde and diethyl malonate with acetonitrile to give 14 (equation 37). 

This review is written to cover the needs of synthetic chemists with interests in oxidizing alkenes by addition of nitrogenous substituents. Whilst some aspects have been covered in previous reviews (noted in the text), most notably in the Tetrahedron Report No. 144, Amination of Alkenes and prior reviews on aziridines and nitrenes, the present review is the fust conq>ilation of references to the whole range of these particular bond-forming processes. A review by Whitham provides a useful general introduction to reaction mechanisms of additions to alkenes in greater detail than can be covered here. The oxidation requirement excludes from the scope the additions of N H and most additions of N + Metal or N + C. Hence, unmodified Michael and Ritter reactions are excluded. These topics are mostly covered in Volume 4 of the present series. 

A Ritter-type reaction is also observed during the anodic oxidation of phenylthio-methane derivatives [186] of the type shown in Eq. (55), which summarizes the proposed reaction mechanism. 

The mechanism of the reaction is illustrated in Scheme 1 for the conversion of r-butanol, using sulfuric acid and acetonitrile, into A -r-butylacetamide. Three intermediates are involved. Firstly, a carbenium ion (1) is produced under strongly acidic conditions. This reacts with the nitrile to produce a resonance-stabilized nitrilium ion (2), which in turn is converted into the corresponding imidate (3). Finally, the latter is hydrolyzed to the amide. Since all three events occur in a one-pot process, frequently in high yield, the Ritter reaction is a simple, efficient and general synthetic procedure. 

Reports of five-membered ring formation involving this mechanism remain unauthenticated. Formation of an oxazolidinone product from Ritter reaction of cyclohexanone and cyclohexanone cyanohydrin has been shown by Ducker to result from an alternative pathway. Although 4-methyl-3-pentenonitrile did undergo intramolecular cyclization, this did not involve pyrrolidone formation. Rather a novel dimeric process took place, leading to formation of a monocyclic (74) and a bi-cyclic (75) product. The latter was readily ring opened to (74) using silver oxide and water (Scheme 37). 

Hessley, R. K. Computational investigations for undergraduate organic chemistry predicting the mechanism of the Ritter reaction. J. Chem. Educ. 2000, 77, 202-205. 

Colombo, M. I., Bohn, M. L., Ruveda, E. A. The mechanism of the Ritter reaction in combination with Wagner-Meen/vin rearrangements A... 

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