Formation of C-N Bonds and Related Reactions

The catalytic effect of quaternary ammonium salts in the basic liquid liquid two-phase alkylation of amines [1-3] is somewhat unexpected in view of the low acidity of most amines (pKfl 30). Aqueous sodium hydroxide is not a sufficiently strong base to deprotonate non-activated amines in aqueous solution and the hydroxide ion is not readily transferred into the organic phase to facilitate the homogeneous alkylation (see Chapter 1). Additionally, it is known that ion-pairs of quaternary ammonium cations with deprotonated amines are decomposed extremely rapidly by traces of water [4]. However, under solidrliquid two-phase conditions, the addition of a quaternary ammonium salt has been found to increase the rate of alkylation of non-activated amines by a factor of ca. 3-4 [5]. Similarly, the alkylation of aromatic amines is accelerated by the addition of the quaternary ammonium salt the reaction is accelerated even in the absence of an inorganic base, although under such conditions the amine is deactivated by the formation of the hydrohalide salt, and the rate of the reaction gradually decreases. Hence, the addition of even a weak base, such as 

Base Catalyst mmol of base % yield With catalyst Without catalyst  

It is noteworthy that benzyltriethylammonium chloride is a slightly better catalyst than the more lipophilic Aliquat or tetra-n-butylammonium salts (Table 5.2). These observations obviously point to a mechanism in which deprotonation of the amine is not a key catalysed step. As an extension of the known ability of quaternary ammonium halides to form complex ion-pairs with halogen acids in dichloromethane [8], it has been proposed that a hydrogen-bonded ion-pair is formed between the catalyst and the amine of the type [Q+X—H-NRAr] [5]. Subsequent alkylation of this ion-pair, followed by release of the cationic alkylated species, ArRR NH4, from the ion-pair and its deprotonation at the phase boundary is compatible with all of the observed facts. 

It has been reported that the ease of A-alkylation of aromatic amines is enhanced by ultrasonics [9], and, predictably, the presence of mesomeric electron-withdrawing substituents at positions ortho or para to the amino function aids the A-alkylation of the aromatic amines [e.g. 10], see also, for example, the phase-transfer catalysed glycosidation of 2-cyanoaniline [11], Generally, the direct /V-monoalkylation of aminoarenes is not particularly satisfactory, but an alternative protocol [12] in which the N-acyl derivatives are alkylated and then hydrolysed leads to enhanced yields ( 90%) (see Section 5.2). In a similar manner, a one pot synthesis converts 2- 

Amine Catalyst % conversion11 % yield A-alkylation A./V-dialkylation  

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