Halo amines, alkylation preparation

Among compounds other than simple alkyl halides a halo ketones and a halo esters have been employed as substrates m the Gabriel synthesis Alkyl p toluenesul fonate esters have also been used Because phthalimide can undergo only a single alkyl ation the formation of secondary and tertiary amines does not occur and the Gabriel synthesis is a valuable procedure for the laboratory preparation of primary amines... 

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... 

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

Support-bound alkylating agents have been used to N-alkylate pyridines and dihydropyridines (Entries 7 and 8, Table 15.21). Similarly, resin-bound pyridines can be N-alkylated by treatment with a-halo ketones (DMF, 45 °C, 1 h [267]) or other alkylating agents [246]. Polystyrene-bound l-[(alkoxycarbonyl)methyl]pyridinium salts can be prepared by N-alkylating pyridine with immobilized haloacetates (Entry 8, Table 15.21). These pyridinium salts react with acceptor-substituted alkenes to yield cyclopropanes (Section 5.1.3.6). Pyridinium salts have also been prepared by reaction of resin-bound primary amines with /V-(2,4-dinitrophenyl)pyridinium salts [268,269]. 

The limitations of this approach can be seen in the reaction of a saturated solution of ammonia in 90% ethanol with ethyl bromide in a 16 1 molar ratio, under which conditions the yield of primary amine was 34.2% (at a 1 1 ratio the yield was 11.3%). Alkyl amines can be one type of substrate that does give reasonable yields of primary amine (provided a large excess of NH3 is used) are a-halo acids, which are converted to amino acids. A-Chloromethyl lactams also react with amines to give good yields to the A-aminomethyl lactam. Primary amines can be prepared from alkyl halides by 10-43, followed by reduction of the azide (19-32), or by the Gabriel synthesis (10-41). 

In primary synthesis 2-perimidinamines (660) can be prepared from the naphthalene diamine with bromocyanogen or cyanamide (Scheme 106). 2-Anilino derivatives have been obtained in reactions with aryl isothiocyanates. 2-iV,7V-Dimethylamino derivatives (662) have been obtained via the alkylated amine (661) using dimethylamino(trichloro)methane. Nucleophilic substitution by amine readily occurs in the 2-position when carrying a halo, sulfenyl, or sulfonyl substituent <81RCR816>. 

A -Halogenation of tertiary amines occurs readily, but in aqueous solution one or two of the alkyl groups are eliminated as aldehydes The usual chlorinating agents are hypochlorous acid or calcium hypochlorite while A-bromination can be brought about by molecular bromine. The first product is an iV-halo quaternary halide (equation 44). The chloro compounds have also been prepared by Bohme ... 

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