Ammonia with alkyl halides

Alkylamines are, in principle, capable of being prepared by nucleophilic substitution reactions of alkyl halides with ammonia. 

A C—N disconnection of a primary amine gives rise to the carbocation and amide anion synthons. It might be predicted therefore that treatment of an alkyl halide with ammonia (reagents equivalent to the above synthons) under pressure would constitute a suitable synthesis of a primary amine. In practice, however, the yield is poor since a mixture of all three classes of amines, together with some of the quaternary ammonium salt, is obtained, owing to more ready further alkylation of the sequentially formed products. 

Subsequent hydrolysis releases a primary amine (Following fig.). Still other possible method is to react an alkyl halide with ammonia, but this is less satisfactory because overalkylation is possible. The reaction of an aldehyde with ammonia by reductive animation is another method of obtaining primary amines. 

Amines may be prepared by the nucleophilic substitution of alkyl halides with ammonia or other amines, by the reduction of imines, nitriles, amides, oximes or nitro compounds or by the rearrangement of amides. 

It will be recalled that the primary amines are substitution products of the hydrocarbons in which an (—NH2) group, called the amino group, has been substituted indirectly for a hydrogen of the hydrocarbon. They are prepared by treating an alkyl halide with ammonia. 

Reactions.—The halogen acids react also like alkyl halides. With ammonia they yield amino acidsy and with potassium cyanide the products are cyanogen acids, or nitriles. 

The problem with displacement of alkyl halides with ammonia is not that the reaction doesn t wori but that it works too well. The primary amine RNH2 is more nucleophilic than ammonia and react again and so on until a useless mixture of primary, secondary, and tertiary amines is formed. 

Reacting an alkyl halide with ammonia (NH3) replaces the halogen atom with an amino group (-NH2), forming an alkyl amine, as shown in the following equation. 

Reductive amination of a ketone is almost always a better method for the synthesis of an amine of the type R "NH2 than treatment of an alkyl halide with ammonia. Explain why this is true. 

Amines are prepared by the reaetion of an alkyl halide with ammonia or another amine. Polyalkylation of an amine during reaetion with alkyl halides is a serious problem. 

The preparation of pure primary amines by the interaction of alkyl halides and ammonia is very difficult, because the primary amine which is formed reacts with unchanged alkyl halide to give the secondary amine the latter... 

By heating an alkyl halide with an alcoholic solution of ammonia in a sealed tube, a mixture of amines is formed by nucleophilic substitution reaction. 

All acetylenes with a terminal triple bond are instantaneously converted into the alkali acetylides by alkali amides in liquid ammonia. For many alkylations with primary alkyl halides liquid ammonia is the solvent of choice and the functionalization with oxirane can also be carried out in it with good results. Reactions of ROOM with sulfenyladng agents (R SSR1, R SON, R SSC R ) or elemental sulfur, selenium or tellurium are mostly very successful in ammonia, the same holds for the preparation of ROC1 from RC=CM and iodine. The results of couplings with carbonyl compounds are very variable. 

So the reaction of an alkyl halide with NaSH or Na2S cannot usually be made to stop after one alkylation as the anion of the first product is at least as nucleophilic as HS or S2. This is obvious in reactions with Na2S. Less obviously with NaSH the first reaction 18 gives the thiol 19 but this is in equilibrium with RS- and a second displacement 20 gives the sulfide 21. We shall see shortly how to get round this problem. A more important example—the failure of the alkylation of ammonia to give a useful amine synthesis—has chapter 8 to itself. 

Ammonia and other amines are good nucleophiles in s2 reactions. As s result, the simplest method of alkytamine synthesis is by alkylation f ammonia nr an alkylamine with an alkyl halide. If ammonia is used, s pri-... 

One common present day preparation of dialkyl mono-and ditellurides involves the reaction of alkyl halides with alkali metal tellurides that have been prepared in situ. The reactions are commonly carried out in aqueous or nonaqueous solutions. Solutions of sodimn in liquid ammonia also provide a useful media for the reduction of tellurium. ... 

Primary amines can also be prepared by the reaction of an alkyl halide with azide ion, followed by catalytic hydrogenation. What advantage do this method and the Gabriel synthesis have over the synthesis of a primary amine using an alkyl halide and ammonia ... 

The next step in the sequence has "A" reacting with an alkyl halide, CH3CH2CH2Br. The alkyl halide reacts in a similar manner to reaction of halides with ammonia or amines as shown q... 

STRATEGY AND ANSWER Consider the structure of the required alkyl halide. Reaction of a secondary halide with ammonia would inevitably be accompanied by considerable elimination, thereby decreasing the yield of the secondary amine. Multiple //-alkylations may also occur. 

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