Halides, alkyl reaction with hexamethylenetetramine

SOMMELET REACTION. Preparation of aldehydes from aralkyl or alkyl halides by reaction with hexamethylenetetramine followed by mild hydrolysis of the formed quaternary salt,... 

An alkyl halide 1 reacts with hexamethylenetetramine 2 to the quaternary ammonium salt 4, which crystallizes from the reaction mixture ... 

Primary amines through reaction of alkyl halides with hexamethylenetetramine... 

Reaction of alkyl halides 1 with hexamethylenetetramine 2 (trivial name urotropine) followed by a hydrolysis step, leads to formation of primary amines 3 free of higher substituted amines. This method is called the Delepine reaction, a comparable method is the Gabriel synthesis. 

Normally the reaction Is useful for the conversion of alkyl halides to primary amines without concomitant formation of secondary amines.29 Treatment of polymer 17 with hexamethylenetetramine in a mixture of ethanol/THF afforded an insoluble resin. Using diazabicyclooctane (DABCO), we demonstrated that the reaction could be limited to attack by a single nitrogen in a multifunctional amine, so we did not anticipate crosslinking via bis-quat salt formation. Hydrolysis of 2 with anhydrous HC1 in ethanol generated free amino groups as evidenced by a positive ninhydrin test, but quantitative hydrolysis could not be achieved and the product remained insoluble. One would have expected a simple bis-quat to hydrolyse and open the crosslinked structure. 

Another way to oxidize primary alkyl halides to aldehydes is by the use of hexamethylenetetramine followed by water. However, this reaction, called the Sommelet reaction. is limited to benzylic halides. The reaction is seldom useful when the R in RCH2CI is alkyl. The first part of the reaction is conversion to the amine ArCH2NH2 (0-44), which can be isolated. Reaction of the amine with excess hexamethylenetetramine gives the aldehyde. It is this last step that is the actual Sommelet reaction, though the entire process can be conducted without isolation of intermediates. Once the amine is formed, it is converted to an imine (ArCH2N=CH2) with formaldehyde liberated from the reagent. The key step then follows transfer of hydrogen from another mole of the arylamine to the imine ... 

Delepine reaction. Preparation of primary amines by reaction of alkyl halides with hexamethylenetetramine followed by acid hydrolysis of the formed quaternary salts. 

In 1913, Marcel Sommelet (1877-1952) of the Faculty de Pharmacie of Paris University published his seminal article in Comptes Rendus with the title Decomposition of Alkyl Halide Addition Products of Hexamethylenetetramine, where he delineated the formation of aldehydes by treatment of benzyl halides followed by hydrolysis.4,5 In 1954, S. J. Angyal published a review in Organic Reactions, where he summarized the mechanism, scope, and limitations of the Sommelet reaction.1 Angyal s review ignited a flurry of research and the Sommelet reaction became a well-known standard for the transformation of benzyl halides to the corresponding benzaldehydes. 

However, it is worth returning to the chemistry of hexamethylenetetramine (1,3,5,7-tetraazaadamantane or l,3,5,7-tetraazatricyclo[3.3.1.H ]decane, C6H12N4, Chapter 9 and Table 10.2) that is formed by the condensation of ammonia (NH3) with methanal (formaldehyde, H2OO). As was noted as early as 1895 by M. Delepine, in a reaction now bearing his name, alkyl halides react with hexamethylenetetramine to produce A-substituted derivatives of the hexamethylenetetramine, which can then be hydrolyzed to aldehyde, ammonia, and substituted amine. Not unexpectedly, it has become clear that benzyhc and allylic halides react best (Scheme 10.30). 

Primary amines can be prepared from alkyl halides by the use of hexamethylenetetramine followed by cleavage of the resulting salt with ethanolic HCl. The method, called the Delepine reaction, is most successful for active halides such as allylic and benzylic halides and a-halo ketones, and for primary... 

The reaction between alkyl halides and hexamethylenetetramine, followed by cleavage of the resulting salt with ethanolic HCl to yield primary amines. 

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