Hexamethylenetetramine, amine alkylation

Although in the dry state carbon tetrachloride may be stored indefinitely in contact with some metal surfaces, its decomposition upon contact with water or on heating in air makes it desirable, if not always necessary, to add a smaH quantity of stabHizer to the commercial product. A number of compounds have been claimed to be effective stabHizers for carbon tetrachloride, eg, alkyl cyanamides such as diethyl cyanamide (39), 0.34—1% diphenylamine (40), ethyl acetate to protect copper (41), up to 1% ethyl cyanide (42), fatty acid derivatives to protect aluminum (43), hexamethylenetetramine (44), resins and amines (45), thiocarbamide (46), and a ureide, ie, guanidine (47). 

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. 

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... 

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. 

Delepine reaction org chem Slow ammonolysis of alkyl halides in acid to primary amines in the presence of hexamethylenetetramine. del-3,pTn re,ak-sh3n deliquescence phys chem The absorption of atmospheric water vapor by a crystalline solid until the crystal eventually dissolves into a saturated solution. del-3 kwes-3ns ... 

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

Conversion of Alkyl Halides to Primary Amines with Hexamethylenetetramine Amino-de-halogenation (overall transformation)... 

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 ... 

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

Alkylation of hexamethylenetetramine gave the corresponding quaternary ammonium salts, which were converted into primary amines without concomitant formation of secondary amines (Deldpine reaction). ... 

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

Synthesis of primary amines from alkyl halides with hexamethylenetetramines (see 1st edition). 

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 cannot be usefully prepared, by reductive alkylation, from lower members of the aliphatic aldehydes and ammonia owing to side-reactions (for instance, formaldehyde and ammonia give hexamethylenetetramine). For aldehydes with more than five carbon atoms, however, conversion to the corresponding amine gives 60% yieldsEven better yields are reported for aromatic aldehydes, presumably because of the greater ease of imine formation With an excess of aromatic aldehyde the reaction with ammonia invariably leads to formation of the secondary amine but with aliphatic compounds a mixture of primary and secondary amines is generally obtained. Alternatively, secondary amines can be prepared directly from primary amines (equation 35). 

In Chapter 9, we used the reagent hexamethylenetetramine, 14.24, as an alternative for ammonia in nucleophilic substitutions to prepare amines. This reagent is prepared by condensation of ammonia and formaldehyde. Draw out the fundamental reactions that are necessary to build this caged structure. When the nitrogen has substituted an alkyl halide, the product is converted to the amine by acid hydrolysis. Draw out the key steps in this process. 

There are also many syntheses that involve nucleophilic substitution using a synthon for ammonia. Thus, the azide anion is an excellent nucleophile, and alkyl azides are readily reduced to amines (Figure 22.5), either by hydrogenation, as in this example, or by reduction with lithium aluminum hydride. Hexamethylenetetramine is also an excellent nucleophile and a synthon for ammonia in this case, the final product is released by hydrolysis (Figure 22.6). In the Gabriel synthesis, phthalimide acts as a synthon for ammonia (Figure 22.7). 

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