Methylaniline amines:alkyl anilines

A AlI lation. A number of methods are available for preparation of A/-alkyl and A[,A/-dialkyl derivatives of aromatic amines. Passing a mixture of aniline and methanol over a copper—zinc oxide catalyst at 250°C and 101 kPa (1 atm) reportedly gives /V-methylaniline [100-61-8] in 96% yield (1). Heating aniline with methanol under pressure or with excess methanol produces /V, /V-dimethylaniline [121 -69-7] (2,3). 

N-Alkylation of primary aromatic amines increases their nucleophilic character, making them couple much more readily, the introduction of the azo group occurring in the 4-position. Thus, in contrast to aniline, N-methylaniline couples readily and N,N-dimethyl-aniline very readily with simple diazonium salts. Diphenylamine also couples in the 4-position, but less readily than N-methylaniline. 

As indicated above, tertiary aromatic amines are directly C-nitrosated. The usual reagents are sodium nitrite and dilute hydrochloric acid, sodium nitrite and glacial acetic acid containing concentrated hydrochloric acid, and nitrite esters with hydrochloric acid [21a, 27]. While tertiary amines with such complex alkyl groups as found in A,A-di(3,5,5-trimethylhexyl)aniline are readily nitrosated [25], of the four A-butyl-A-methylaniline isomers, JV-r-butyl-A-methylaniline does not undergo the reaction, and even the nitroso compounds which did form were only unstable oils [27]. 

The proton-proton HNCH spin-spin coupling in A-methylaniline is affected by the p fa value of the proton acceptor partner. PhsPO, PhsAsO and F ions are used in order to elucidate this dependence. The importance of the hydrogen bonding interaction is observed also in aniline reactions. In fact, the addition of potassium fluoride to the reaction mixtures of anilines and alkyl halides strongly enhances the A-alkylation reaction because the nucleophilicity of aromatic amines is increased by hydrogen bond interaction with fluoride ion151. 

Methylaniline, C6H5.NHCH3, is an example of a secondary amine which contains an aryl and an alkyl radical. It is prepared commercially for use in the manufacture of dyes by heating aniline hydrochloride with methyl alcohol under pressure. Methylaniline is an oil, lighter than water, which boils at 192°. 

Following their discovery of the ruthenium-catalyzed A -alkylation of anilines with alcohols to give secondary and tertiary amines (Scheme 1, equation 1) [1], Watanabe and his colleagues adapted their chemistry to a synthesis of indoles as shown in equations 2 and 3 12-5], The reaction of Af-methylaniline with propylene glycol under typical conditions affords 1,2-dimethylindole and 1,3-dimethylin-dole in a 1 1 ratio (50% yield), whereas aniline plus styrene glycol gives only 2-phenyUndole (43% yield) [4], The best yield was 89% for the preparation of 5-chloro-2,3-dimeth-ylindole (equation 2). 

As would be expected, the pJ a values of alkyl-substituted derivatives of A -methylaniline vary from that of the parent amine in a similar manner to those of the corresponding aniline derivatives when there is not more than one ortho substituent, but follow more closely the... 

N-Alkylation of aniline with [(NHC)Ir] complexes was first reported with catalyst 36a. Employing KOH or t-BuOK as stoichiometric base, better yields of the monoalkylated produet were obtained than with the parent complex [IrCl2Cp ]2. Furthermore, upon using the pyrimidine-containing complex 37 as catalyst, a weak base such as NaHCOs was sufficient to promote the reaction. The combination of complex 35a with AgOTf afforded a very active catalytic system, which did not require any added base, and was also very active in the benzylation of the secondary amine N-methylaniline. The resulting drawback was a certain lack of... 

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