Delepine reaction

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. 

The Delepine reaction is a useful synthetic method, since it permits the selective preparation of primary amines from simple starting materials under simple reaction conditions and with short reaction time. 

This method gives better yields than other methods of preparation of 2-bromoallylamine, and it is the most convenient method for the preparation of large quantities of the compound. The procedure illustrates a reaction, the so-called Delepine reaction, that has been used for the preparation of many primary aliphatic amines.8-12 A number of primary aliphatic amines have been prepared by this method without isolation of the intermediate hexaminium salt.11 Several preparations of aliphatic aldehydes via the hexaminium salt have been described in earlier volumes of this series.13... 

Delepine reaction, to prepare 2-bromo-allylamine, 43, 6 Deoxyanisoin, 40,16 Deoxybenzoin, 40,17 Deoxypiperoin, 40,17 Desylamine, 41, 87... 

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... 

Conversion of chloromethylated polymers to our second target system, aminomethylated polymers, was approached In several different ways. Two of the approaches, which were used successfully to convert model compound 11 to the desired amlnomethyl products failed when applied to the polymer system. The first of these, the Delepine reaction, appeared to be the most reasonable and economical, but only Insoluble, apparently crosslinked products could be Isolated. 

The Delepine reaction Involves nucleophilic displacement of active halides by hexamethylenetetramine, followed by hydrolysis of Intermediate quaternary ammonium salt to release the amine. 

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 ... 

However, with liquid ammonia or anhydrous methylamine 1,2,4-oxadiazines (88) are formed. 5-(Chloromethyl)-l,2,4-oxadiazoles (e.g., (86) react with urotropin to form salts, which are hydrolyzed with hydrochloric acid to 5-(aminomethyl) compounds (the Delepine reaction). Alternatively, 5-(aminomethyl)-l,2,4-oxadiazoles have been prepared by condensation of amidoximes with a-amino-acids <72JHC435>. 

Phenacylamine hydrochloride has been prepared by (1) the hydrolysis of the quaternary salt obtained from phenacyl bromide and hexamethylenetetramine (the Delepine reaction),6-11 (2) the hydrolysis of N-phenacylphthalimide (the Gabriel reaction),12-14... 

Of the procedures cited in Section 3, procedures (1), (3), and (4) have been examined by the submitters for comparison with the present procedure. Of these, the present procedure and that based on the Delepine reaction (1) appeared to be the most satisfactory for preparative purposes. Yields by the two procedures were comparable however, the Delepine reaction could be run somewhat more conveniently on a larger scale (provided that one was willing to accept a tedious extraction of the product from the copious quantity of ammonium salts with which it is mixed). The Delepine reaction also makes a lesser demand on the skill and technique of the operator. On the other hand, attempts in the submitters laboratory to extend the Delepine reaction to sec-bromides have been unsuccessful therefore the Delepine reaction appears to lack the generality of the present procedure, which shares such generality, apparently, with procedures (2), (3), (7). and (8). Furthermore, the Delepine reaction gives a mixture of phenacylamine hydrochloride and hydrobromide M0 (although the submitters have found that by careful fractional crystallization from isopropyl alcohol-hydrochloric acid solution about 50% of the pure hydrochloride can be obtained). 

Dealkylation of tertiary amines with dibenzoyl peroxide, 44, 74 Decarboxylation, intermolecular, of isocyanates to carbodiimides, 43,32 Decker synthesis of amines, 44, 7t, 75 Dehalogenation of l,l,2-trichloro-2,3,3-trifluorocydobutane, 42,45 Dehydration, of formamides with phosphorus oxychloride to isocy-anides, 41, 13, 101 of 4- 2-hydroxyethyl)piperidine to quinuclidine, 44, 90 Dehydrohalogenation of 2-chloroallyl-amines to propargylamines, 44,55 Delepine reaction, to prepare 2-bromo-allylamine, 43, 6 Deoxyanisoin, 40,16 Deoxybenzoin, 40, IT Deoxypiperoin, 40, IT Deaylamine, 41, 8T... 

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

The synthesis of aminomethylpolystyrene by the Delepine reaction [24] of cross-linked chloromethylpolystyrene (XE-305 type) using hexamethylenetetramine (HMTA) followed by acidic hydrolysis (Scheme 2) wa.s first described in thi.s laboratory [25]. The conversion of the -CH,C1 to CHjNH, proceed.s very well within a range of chloromethyl group concentrations on the polymer ranging from 7 to 82 mole percent (see Table 1), and reaches 98T conversion starting from chloromethyl... 

Conversion o f(2)-CHjCI (XE-3()5) to ( l-CH NH, via a Delepine reaction with hexamethylenetetramine (ElMTA) followed bv hvdrolvsis... 

One-step functionalization of aminomethylpolystyrene, type 4, prepared by the Delepine reaction, or by other routes, with various ligands carrying a benzylic halide group i.s shown in Scheme 3. Reaction of polymers of type 4 (4A, Z = H 4B, Z = Br 4C, 2% DVB, gel-type copolymer) with 2-acetyl-4-chloromethylphenol or 4-chloro-methyl-2-formylphenol (2-acyl-4-chlorometh-ylphenoLs are stable at acidic pH [31]) in CHClj, followed by oximation, yields the hydroxyoxime polymers of type.s 5 (66% conversion) and 6 (48% conversion), respectively. 

The Delepine reaction or the Del6pine amine synthesis is the closest variation of the Sommelet reaction. The Delepine amine synthesis is the acid hydrolysis of the hexaminium salt 2 with strong acid in ethanol, giving rise to benzylamine 4 with the formaldehyde being removed as volatile formaldehyde diacetal.13-15 In essence, it may be considered as half of the Sommelet reaction or the interrupted Sommelet reaction. The Delepine reaction works well for active halides such as benzyl, ally halides, and a-halo-ketones. 

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