Hydrogen cyanide Ritter reaction

Method 4. Ritter reaction reaction of hydrogen cyanide with an olefin in an acidic medium to produce a primary amine. 

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. 

Mecamylamine Mecamylamine, M2,3,3-tetramethylnorboman-2-ylamine (14.2. 2), is synthesized from 2,3,3-trimethylnorbomen-2, which is reacted in a Ritter reaction conditions with hydrogen cyanide in concentrated snlfuric acid, giving 2,3,3-trimethylnorbor-nan-2-ylformylamine (14.2.1), the reduction of which by lithium aluminum hydride leads to mecamylamine (14.2.2) [32,33]. 

The preparation of amides by the addition of hydrogen cyanide or alkyl nitriles to alkenes in the presence of acids, known as the Ritter reaction, has been reviewed.229-232 The reaction may be considered simplistically as nucleophilic attack of a nitrile on a carbocation formed by the protonation of an alkene. Subsequent hydrolysis of the nitrilium intermediate gives the amide product (equation 164). The overall result is addition of a molecule of H—NHCOR to a C—C double bond. 

Abb. 7.16. Ritter reaction part I (cf. Fig. 7.17) SN1 reaction between a tertiary alcohol and a nucleophile containing C=N, with hydrogen cyanide acting as the nucleophile. Under reaction conditions the C=N group is tert-alkylated at the N atom and hydrated at the nitrile nitrogen leading to the formation of an W-tert-alkyl-formamide (B). 

Ritter Reaction. Mitsubishi Rayon and Sumitomo Chemical in Japan make t-butylamine Reaction (22-57). Average yields are about 85 percent based on isobutylene. Rohm and Haas in the United States makes t-octylamine from hydrogen cyanide and diisobutylene by a similar route.116... 

The precise experimental conditions used can greatly influence the efficiency, or even the course, of the Ritter reaction. Representative procedures are available, along with a comprehensive tabular survey to 1966, in the article by Krimen and Cota. Optimum reaction times (typically 1-24 h) and temperatures (typically 20-50 °C) depend very much on e particular cases. Typical temperatures of 0-10 °C are used when hydrogen cyanide or hydrogen fluoride are employed. Benzenesulfonic, fluoroboric, formic, hydrofluoric, methanesulfonic, perchloric, phosphoric, polyphosphoric, sulfuric, toluenesulfonic and tri-fluoromethanesulfonic acids are amongst those used to generate the carbenium ion. However, the majority of workers favor sulfuric acid and, in cases where comparative studies have been carried out, - ... 

Most tertiary butylamine (and other tertiary alkyl amines) is produced using hydrogen cyanide in the Ritter reaction. Isobutylene [97] or methanol [98] is reacted with hydrogen cyanide under acidic conditions to generate r-butylamine ( 1.46/lb) ... 

The Ritter reaction proceeds by a nucleophilic addition of hydrogen cyanide followed by the hydrolysis of the intermediate formamide. Higher tertiary alkyl amines are produced using the same method with higher alkenes and alcohol. This is considered the most practical way to produce tertiary amines [99]. 

Addition of hydrogen cyanide or nitriles to olefins in the presence of concentrated sulfuric acid or some other strong acid is a preparatively important method of synthesizing alkylated amides containing secondary or tertiary alkyl groups on the nitrogen atom (the Graf-Ritter reaction) 20-26... 

Explain why in the Ritter reaction with hydrogen cyanide and t-butyl alcohol, the product is t-butylamine and not t-butyl cyanide (or trimethylacetic acid). 

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. 

Iminium halides are intermediates in the hydrolysis of nitriles and in a variety of chemical reactions. For example, in the Ritter reaction addition of a nitrile or hydrogen cyanide to a carbonium ion occurs, leading to the intermediate formation of a nitrilium salt. Nitrilium salt intermediates have also been postulated in the Schmidt reaction and in the Beckmann rearrangement, provided the latter was performed in concentrated sulfuric acid. However, since we are predominantly concerned with imidoyl halides, these reactions are not discussed in this monograph. 

In another vein, addition of sulfuric acid to an alkene in the presence of a nitrile (R-C=N) or hydrogen cyanide (HC N), either of which can react with the carbo-cation as a nucleophile, apparently leads to nitrilium ions. These ions, on hydrolysis, produce amides. As amides can be hydrolyzed in acid or basic medium to amines and carboxylic acids, the overall process (the Ritter reaction) of carbocation... 

Scheme 6.41. A representation of the Ritter reaction. Hydrolysis of the iminium ion produces either an amide (as shown for reaction with hydrogen cyanide [HCN] producing the formamide of 2-amino-2-methylpropane [At-ferf-butylformamide (CHslsCNHCHO]) or, further, past the amide to the amine (2-amino-2-methylpropane [2-methyl-2-propananiine, f-butylamine, (CH3)3CNH2] and the corresponding (unspecified and thus unnamed) carboxylic acid (R-CO2H).

For preparative purposes, Ritter s original procedure of generating the carbonium ion from the alcohol (or olefin) and sulphuric acid is preferred under these conditions, hydrogen cyanide, produced in situ from sodium cyanide, can replace the nitrileSecondary and tertiary alcohols can be used" , and the reaction, providing essentially for substitution by the 5 1 mechanism, is a valuable addition to the methods already discussed. It must be borne in mind, however, that under certain conditions carbonium ion rearrangement is possible, and has indeed been observed in some applications of this reaction... 

Further examples of the Ritter reaction(cf. section IV.B) are provided by the many substituted olefins that may be protonated to ve carbonium ions which can be intercepted by hydrogen cyanide or organic nitriles cyanogen chloride can also be used as intercepting species , but offers no advantages. Mixtures of the two possible amides, and hence amines, are to be expected from non-terminal alkenes and from such olefinic compounds as oleic acid Olefins may also be converted to amines with yields of up to 60%, by hydroboration and subsequent reaction of the organoborane with chloroamine in alkaline solution or preferably with hydroxylamine-0-sulphonic acid in diglyme (reaction 86) The reaction is applicable... 

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