Ritter reaction amination

Various modifications of the reaction of an alcohol with ammonia provide the most common commercial routes to alkylamines. Some others routes that are used to make certain individual amines include aldehyde/amine additions, nitrile reduction, the Ritter reaction, amination of isobutylene, and hydrogenation of anilines. Capacities of many plants depend on the product mix of mono/di/tri products as well as the variety of amines (ethyl, propyl and butyl). One must know the product mix that the capacity is based upon and the actual scheduled output of produces) to determine what amounts can actually be manufactured. Capacities are often in excess of anticipated demand to satisfy seasonal demands for pesticide uses116. 

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. 

Other sequences that transform primary alcohols to primary amines include (a) conversion of the alcohol to a cyanate, rearrangement to an isocyanate, and hydrolysis,3 and (b) conversion of the alcohol to an -V alkylformamide via the Ritter reaction, followed by hydrolysis.4... 

PhentEimine (11),used in the treatment of obesity, is a t-alkyl amine. The Ritter reaction, using HCN as the nitrile (p T63), is ideal for this,... 

This procedure constitutes the first example of one-step conversion of a /-alkane to the corresponding /-alkyfamine. Other hydrocarbons in this class, such as isobutane, have also been aminated with good results.7 Only a very limited number of convenient routes, e.g., the Ritter reaction, are available for the preparation of /-carbinamines. The present preparation illustrates a simple method that utilizes a novel substrate. 

There are several methods available for the electrophilic addition of hydrogen and nitrogen to alkenes, dienes and alkynes. While the direct electrophilic addition of amines to these substrates is not feasible, aminomercuration-demercuration affords a very useful indirect approach to such amines. The addition of amides to C—C multiple bonds can be effected directly through the Ritter reaction or by the less direct, but equally useful, amidomercuration-demercuration process using either nitriles or amides. Similarly, H—N3 addition to alkenes can be carried out directly or via mercuration to produce organic azides. 

The Ritter reaction (42,42A) is a general method for converting alcohols to amines by reaction with a nitrile and a strong acid (Reaction XXVI). In this reaction only tertiary,... 

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. 

If the reactions are carried out in a nitrile as solvent, rather than dichloromethane, using triflic acid as catalyst, a modified Ritter reaction takes place, and the intermediate nitrilium ion traps the liberated amine, forming an amidine (Scheme 67). In an earlier reaction cf. Scheme 67) the lithium perchlorate catalyzed reaction of sulfenyl chlorides with alkenes in the presence of nitriles had also given l-amido-2-sulfenyl adducts. Ritter products are also obtained in good yields by anodic oxidation (Pt or C, 1.2-1.4 V) of disulfides in acetonitrile, in the presence of excess alkene, using B114NBF4 as supporting electrolyte (Scheme 68). ... 

Functionality adjacent to the epoxide can modify its reactivity. For example, 2,3-epoxy sulfides can be converted to a thiiranium species upon treatment with TMS triflate. This intermediate reacts with 0-silyl amides regiospeci-fically to form l-substituted-3-hydroxy-2-thioethers. Simple primary amines undergo polyalkylation, but imines can be used as an indirect amine equivalent <1996T3609>. Nitriles react with functionalized oxiranes in a regioselective manner in a tandem epoxide opening-Ritter reaction (Equation 17) <2005JOC7447>. 

Since the amides (especially the formamides) are easily cleaved under hydrolysis conditions to amines, the Ritter reaction provides a method for achieving the conversions R OH R NH2 (see 10-32) and alkene R NH2 (see 15-8) in those cases where R can form a relatively stable carbocation. The reaction is especially useful for the preparation of tertiary alkyl amines because there are few alternate ways of preparing these compounds. The reaction can be extended to primary alcohols by treatment with triflic anhydride ° or Ph2CCl" SbClg or a similar salt in the presence of the nitrile. 

A mechanistic limitation of the Ritter reaction is that, while N-alkylformamides (and thence primary amines) are readily available, further direct substitution on nitrogen is mled out. However, simple A-al-kylation of the formamide may be performed utilizing phase-transfer catalysis. This provides a conven-... 

Tertiary alcohols tend to react without rearrangement while secondary alcohols are liable to do so, equations (14) and (15), as discussed in Section 1.9.1.2. Primary alcohols normally fail to react with nitriles even under severe conditions, but this restriction does not apply to benzylic examples (equation 16). In appropriate cases," the Ritter reaction can be stereoselective (Scheme 10). Either alcohol isomer, separately or as a mixture, gave identical mixtures of the two amine products, showing that axial attack on the cation was predominant. 

Acidic hydrolysis of isonitriles proceeds in two steps to the N-formamide and subsequently to the amine derivatives in common with nitrilium ions produced in the Ritter reaction using hydrogen... 

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