By the Ritter reaction

Ritter Reaction (Method 4). A small but important class of amines are manufactured by the Ritter reaction. These are the amines in which the nitrogen atom is adjacent to a tertiary alkyl group. In the Ritter reaction a substituted olefin such as isobutylene reacts with hydrogen cyanide under acidic conditions (12). The resulting formamide is then hydroly2ed to the parent primary amine. Typically sulfuric acid is used in this transformation of an olefin to an amine. Stoichiometric quantities of sulfate salts are produced along with the desired amine. 

Alkenes of the form RCH=CHR and RR C=CH2 add to nitriles in the presence of mercuric nitrate to give, after treatment with NaBHj, the same amides that would be obtained by the Ritter reaction. This method has the advantage of avoiding strong acids. 

The first synthesis of a heterocyclic system (22) by the Ritter reaction was reported24 in 1952, from the reaction of nitriles with methyleugenol (19). The reactions succeed only when the benzene ring is activated and allylbenzene itself gives the expected amide. 

Acid-catalyzed nucleophilic addition of a nitrile to a carbenium ion generated from alcohol (usually tertiary primary alcohols other than benzyl alcohol will not react), yielding an amide. Sanguigni, J.A. and Levine, R., Amides from nitriles and alcohols by the Ritter reaction, J. Med. Chem. 53, 573-574, 1964 Radzicka, A. and Konieczny, M., Studies on the Ritter reaction. I. Synthesis of 3-/5-bartbituryl/-Ipropanesulfonic acids with anti-inflammatory activity, ArcA Immunol. Ther. Exp. 30,421 32,1982 Van Emelen, K., De Wit, T., Hoomaert, G.J., and Compemolle, R, Diastereoselective intramolecular... 

Hydration can also be accomplished by the Ritter reaction (treatment with t-butanol in sulfuric acid-acetic acid). 

A -(2-Methylbut-3-yn-2-yl)acetamide (39) (prepared by the Ritter reaction of acetonitrile with 3-hydroxy-3-methylbut-l-yne) on hydrolysis with sulfuric or hydrochloric acid in methanol, basified and steam distilled, gave 2,2,3,5,5,6-hexamethyl-... 

Thibault-Starzyk, F., Payen, R., Lavalley, J.-C. IR evidence of zeolitic hydroxy insertion in amide formation by the Ritter reaction. Chem. 

An efficient synthesis of amides by the Ritter reaction of alcohols and nitriles under MW irradiation was developed under solvent-free conditions (Scheme 8.36). This green protocol is catalyzed by solid-supported Nafion NR50 with improved efficiency and reduced waste production." ... 

Amines of this type can be prepared by the Ritter reaction in which an alkene or alcohol is reacted with hydrogen cyanide or a nitrile in the presence of sulfuric acid. In the case of t-butyl alcohol and hydrogen cyanide, the carbocation that is formed coordinates the nitrogen of the cyano group forming a new C-N bond. A C-N bond is formed rather than a C-C bond because it is the nitrogen that has a free pair of electrons and not the carbon. Therefore, only the nitrogen will attach to the electropositive carbon. 

If the reaction is carried out in acetonitrile then the carbocation is converted into the corresponding amide by the Ritter reaction. 2-Methybutane reacts with nitronium tetrafluoroborate in acetonitrile solution to provide the corresponding amide in moderate yield. 

Interactive mechanism for the fonnation of c/s-aminoindanol by the Ritter reaction... 

An appealing alternative to the substitution with azide is provided by the Ritter reaction with benzonitrUe, from which the oxazolines can be isolated as well. [324, 330] It is interesting that the Ritter reaction produces a high (18 1) diastereo-meric ratio. It may be assumed that the configuration of the benzyl cation is stabilised by the neighbouring hydroxy-group in the a-position. 

Nitrogen-containing compounds are also prepared by the Ritter reaction (see Section (d)). 

Recently, Rapolu et al. (2013) synthesized primary amides by the Ritter reaction of secondary and tertiary alcohols with nitriles catalyzed by SSA catalyst in toluene at 90°C (Scheme 5.55). As the catalyst is cost-effective, stable to air, and recyclable, the present method constitutes a noteworthy modification to the Ritter reaction for the synthesis of amides. Under these conditions, a variety of amines including sterically hindered amines were successfully reacted to form the corresponding amides in excellent yields. The reaction was observed to be chemoselective in nature. Mirjalilia and Sadeghi (2009) studied the Ritter reaction under solvent-free conditions (Scheme 5.56). 

Other Sulfonic Acids. Extensive development work has been conducted on acrylic sulfonate-containing monomers. 2-Sulfoethyl methacrylate (SEM) monomer 5Ahas proved to be of limited commercial value owing to the hydrolytic instability of the ester linkage. However, recently well-defined homopolymers of 3-sulfopropyl methacrylate (SPMA) were prepared under aqueous RAFT conditions with 4-cyanopentanoic acid dithiobenzoate and V-501 as the CTA/initiator pair at 70°C (39). This same hydrolytic instability has been a serious problem with 3-sulfo-2-hydroxypropyl methacrylate. In contrast, 2-acrylamido-2-methylpropanesulfonic acid (AMPSA) 6A, prepared by the reactions of SO3 with isobutylene followed by the Ritter reaction with acrylonitrile (134), is quite hydrolytically stable. 

Other Anionic Carboxyiate Monomers. The anionic carboxylate monomers 8A and 9A, prepared by the Ritter reaction involving acrylonitrile or methacrylonitrile and 3,3-dimethylacrylic acid have been copolymerized in the sodium salt form to yield calcium-tolerant copoljnners with utility in enhanced oil recovery (145-148). Monomer 8A, for example, has been copol5unerized with 7A... 

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