Alkylation of ammonia

Because alkylation of ammonia can lead to a complex mixture of products it is used to prepare primary amines only when the starting alkyl halide is not particularly expensive and the desired amine can be easily separated from the other components of the reaction mixture... 

A method that achieves the same end result as that desired by alkylation of ammonia but which avoids the formation of secondary and tertiary amines as byproducts is the Gabriel synthesis Alkyl halides are converted to primary alkylamines without contam mation by secondary or tertiary amines The key reagent is the potassium salt of phthal imide prepared by the reaction... 

The reaction of amines with alkyl halides was seen earlier (Section 22 7) as a complicat ing factor in the preparation of amines by alkylation of ammonia... 

Ammonia can act as a nucleophile toward primary and some secondary alkyl halides to give primary alkylamines Yields tend to be modest because the primary amine IS itself a nucleophile and undergoes alkylation Alkylation of ammonia can lead to a mixture containing a primary amine a secondary amine a tertiary amine and a quaternary ammonium salt... 

Diphenylisoinclole (29) can be prepared by a modified Leuckart reaction of o-dibenzoylbenzene (46), using an ammonium salt of formic acid the process is essentially a reductive alkylation of ammonia, accompanied by cyclization, and leads to 29 in 44% yield with ammonium formate, and 47 in 28% yield with methylammonium formate. 1,3-Diphenylisoindole. (29) can also be obtained in good yield by the reaction of 46 with 1,1-dimethylhydrazine. ... 

Alkylation lo yield a leriiary amine may occur easily if the formation involves cyclization (ii). Catalysts may have a marked influence. In reductive alkylation of ammonia wilh cyclohexanones, more primary amine was formed over Ru and Rh and more secondary amine over Pd and Pt. Reduction of the ketone to an alcohol is an important side reaction over ruthenium. 

Ammonia and other amines are good nucleophiles in SN2 reactions. As a result, the simplest method of alkylamine synthesis is by Sn2 alkylation of ammonia or an alkylamine with an alky) halide. If ammonia is used, a primary amine results if a primary amine is used, a secondary amine results and so on. Even tertiary amines react rapidly with alkyl halides to yield quaternary ammonium salts, R4N+ X-... 

Transition-metal- and enzyme-catalyzed alkylations of ammonia and amines with alcohols and diols have been reviewed59. RuCl2(PPh3)3 is a homogeneous catalyst for the reaction of long-chain terminal alcohols with secondary amines to give tertiary amines (equation 22)60. 

Sodium cyanoborohydride NaBIpCN in methanol is the reagent of choice for the reductive alkylation of ammonia, primary aliphatic and aromatic amines and secondary aliphatic amines with aldehydes and relatively unhindered ketones (equation 53). 

Eschweiler-Clarke modification org chem A modification of the Leuckart reaction, involving reductive alkylation of ammonia or amines (except tertiary amines) by formaldehyde and formic acid. esh,vTl-3r klark. mad-o-fo ka-shon ... 

Treatment of aldehydes or ketones with ammonia, primary or secondary amines in reducing media is called reductive alkylation (of ammonia or amines) or reductive amination (of aldehydes or ketones). Reducing agents are most frequently hydrogen in the presence of catalysts such as platinum, nickel or Raney nickel [955], complex borohydrides [705, 954, 955], formaldehyde or formic acid [522]. 

Reductive alkylation of ammonia should give primary amines, reductive alkylation of primary amines secondary amines, and reductive alkylation of secondary amines tertiary amines. In reality, secondary and even tertiary amines are almost always present to varying extents since the primary amines formed in the reaction of the carbonyl compounds with ammonia react with the carbonyl compounds to give secondary amines, and the secondary amines similarly afford tertiary amines according to Scheme 128. In addition, secondary amines may be formed, especially at higher temperatures, by additional reactions shown in Scheme 129. Depending on the ratios of the carbonyl compounds to ammonia or amines, different classes of amines predominate. 

Reductive Alkylation of Ammonia or Amines Hydro,dialkylamino-de-oxo-bisubstitution... 

When an aldehyde or a ketone is treated with ammonia or a primary or secondary amine in the presence of hydrogen and a hydrogenation catalyst (heterogeneous or homogeneous), reductive alkylation of ammonia or the amine (or reductive amination of the carbonyl compound) takes place.165 The reaction can formally be regarded as occurring in the following manner (shown for a primary amine), which probably does correspond to the actual sequence of steps 166... 

Alkylation of ammonia or amines 0-44 Reaction between alkyl halides and hexamethylenetetramine (Dele-pine)... 

Hydrolysis of cyanamides 6-13 Addition of ammonia to aldehydes 6-15 Reductive alkylation of ammonia or amines... 

Alkylation of ammonia is sometimes employed in industrial processes the resulting mixture of amines is separated by distillation. The ultimate starting materials for the industrial preparation of allylamine are propene, chlorine, and ammonia. Write a series of equations showing the industrial preparation of allylamine from these starting materials. (Allylamine has a number of uses, including the preparation of the diuretic drugs meralluride and mercaptomerin.)... 

The alkylation of ammonia, Gabriel synthesis, reduction of nitriles, reduction of amides, reduction of nitrocompounds, and reductive amination of aldehydes and ketones are methods commonly used for preparing amines. 

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