Alkylation, of ammonia and amines

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. 

The direct alkylation of ammonia and amines with olefins in the presence of alkali metals as catalysts was reported by Howk and coworkers (17), The general procedure is shown in the following reaction, where R can be a hydrogen atom or an alkyl or aryl group ... 

Prep>aration of Amines Alkylation of Ammonia and Amines... 

K-I Shimizu, Kanno S, Kon K et al (2014) iV-alkylation of ammonia and amines with alcohols catalyzed by Ni-loaded CaSiOs. Catal Today 232 134—138... 

Ohta H, Uozumi Y, Yamada YM et al (2011) In-water dehydrative alkylation of ammonia and amines with alcohols by a polymeric bimetallic catalyst. Org Lett 13(15) 3892-3895... 

The difficulties associated with direct alkylation of ammonia and amines have led to the development of indirect alkylation procedures designed specifically for the preparation of primary and secondary amines. These depend on the blocking of the required number of sites in the ammonia molecule so as to limit the extent of the alkylation reaction, and fall into two categories depending on whether or not the alkylation step involves the formation of a quatemeuy ammonium ion. 

Limitations are also imposed by the nature of the alkyl group in the alkyl halide. Broadly speaking, the alkyl halides which react with ammonia (or amines) to give amines and quaternary ammonium salts are those which are susceptible to substitution by the 3, 2 mechanism. Amines preparable by this route are consequendy those in which primary or secondary alkyl groups are attached to the nitrogen atom. Attempts at alkylation of ammonia and amines using tertiary alkyl halides are normally frustrated by the occurrence of alternative elimination reactions and such problems are also apparent with other halides in which structural features favour alternative reactions (reaction 24) An important group of tertiary halides which may be... 

A. Hofmann Alkylation of Ammonia and Amines—Treatment of Amines with Halides 13-1. Preparation of n-Butylamine... 

B. Hofmann Alkylation of Ammonia and Amines—Reaction of Tosylates with Amines 13-2. Preparation of iV-Methyldihydropyran-2-methylamine... 

A. HOFMANN ALKYLATION OF AMMONIA AND AMINES—TREATMENT OF AMINES WITH HALIDES... 

Haloform reaction, 59,64-65 Hinsberg reaction, 121 Hofinann alkylation of ammonia and amines, 118-123... 

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 ... 

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

Perhaps the simplest reaction to envisage is the alkylation of a co-ordinated amine. These reactions are well-known and usually occur under strongly basic conditions. It is most likely that these reactions involve deprotonated amido intermediates, and are considered in that context. As we have seen in Chapter 2, the acidity of an amine proton should increase upon co-ordination to a metal centre, and with the charge on that metal. As a consequence, we might expect to see new types of reaction products derived from the amido ligand, particularly with high oxidation state metal complexes. The former effect is indeed the case, and dramatic reduction of the pKa of ammonia and amines is observed upon co-ordination to a metal ion (Table 5-1). 

The Wallach-Leuckart reductive alkylation of ammonia, and primary and secondary amines, by means of aldehydes and ketones, and the methylation of secondary amines according to Clarke and Eschweiler,3160 all possess a reduction step which is very similar to that observed in the reduction of enamines.317... 

Addition of ammonia and amines to epoxides containing one or more polar atoms in the vicinity of the oxide ring has been found to occur more rapidly for the most part than with the corresiN udiriL alkyl-substituted analogs. Glycidol, - epichlorohydriiiJ --... 

Alkylation of ammonia and another amine is, in principle, the most straightforward route to an amine. It is well known, however, that the value of this method in the laboratory is sometimes limited because of concomitant polyalkylation (Scheme 1). 

The final product from such a series of nucleophilic substitution and proton transfer reactions is a tetraalkylammonium halide. TTie relative proportions of the various alkylation products depend on the ratio of alkyl halide to ammonia in the reaction mixture. V atever the starting mixture, however, the product is almost invariably a mixture of alkylated products. For this reason, alkylation of ammonia or amines is not... 

In 2013, Shi and co-workers reported a base- and ligand-liree iV-alkylation of ammonia, primary amines and secondary amines with alcohols catalyzed by an air-and moisture-stable NiCuFeOx catalyst (Scheme 28) [157]. The catalyst can be recovered easily and reused at least 5 times (1st, 94 % 5th, 82 %). A 10 mmol scale... 

Scheme 28 NiCuFeOj complex-catalyzed Af-alkylation of ammonia and primary and secondary amines with alcohols...

Quaternary alkylammonium salts or alkylamines are the cationic surfactants most commonly used in the modification of layered silicates. They are synthesized by complete alkylation of ammonia or amines. Many efforts have been made to produce ammonium surfactants to improve the affinity between the clay mineral and the polymer [3]. Ammonium organoclays undergo thermal degradation at temperatures below or comparable to the melt-processing temperatures of many polymers. 

The preparation of amines and quaternary ammonium salts through displacement of halide ion from alkyl halides by ammonia or amines is commonly referred to as alkylation of ammonia (or amines) alkyl esters of other strong acids have also been used in similar alkylation procedures. Equations (19) to (22) represent in simple terms the sequence of reactions which may occur in the interaction of ammonia or an amine with an alkyl halide. 

It has been tentatively suggested that one mechanism underlies the Willgerodt reaction and the Kindler modification of it. A labile intermediate is first formed which has a carbon—carbon bond in the side chain. The scheme is indicated below it postulates a series of steps involving the addition of ammonia or amine (R = H or alkyl), elimination of water, re addition and eUmination of ammonia or amine until the unsaturation appears at the end of the chain then an irreversible oxidation between sulphur and the nitrogen compound may occur to produce a thioamide. 

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... 

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