N-Chloroamines

N-chloroamine functionalization of the angular methyl group preparation of 3/3-hydroxy-18-chloro-20a-methylamino-5a-pregnan-l l-one trifluoroacetate, 259... 

Not surprising, the most prevalent synthetic utility is the assembly of the pyrrolidine ring. N-Chloroamine 27 was obtained by treatment of N-methyl-2-cyclopentylethylamine (26) with N-chlorosuccinimide. Under classic Hofmann-Loffler-Freytag reaction conditions, 27 was rearranged either thermally or by UV irradiation in sulfuric acid to bicyclic amine... 

Due to the radical nature of the Hofmann-Lbffler-Freytag reaction, a deviation was observed when there was a pendant terminal olefin on the substrate. When the aminyl radical from N-chloroamine 31 had a choice between addition to the double bond... 

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

Aminyl spin adducts were also observed during Ag(0)-promoted dechlorination of N-chloroamines in the presence of MNP (Edwards et al., 1973), but the isolation of silver succinimide from the reaction of N-chlorosuccinimide again suggests that the possibility that these adducts arise by nucleophile trapping cannot be disregarded. 

Some oxaziranes can be prepared very simply from ketones and N-chloroamines. Thus 2-methyl-3,3-pentamethyleneoxazirane is easily obtained from cyclohexanone and iV-methylchloramine its reduction by ferrous salts gives an alkyl radical, which has been used to alkylate, in high yield, protonated heteroaromatic bases in aqueous solution (Scheme 5). 

One example of this type of reaction is the photolytically initiated decomposition of N-chloroamines in acidic solution, which is known as the Hofmann-Loffler reaction,208 The initial products are d-chloroamines, but these are usually converted to pyrrolidines by intramolecular nucleophilic substitution. 

The so-called Hofinann-Loeffler-Freytag reaction" of N-chloroamines 9 proceeds by a similar mechanism, and is for example used for the synthesis of pyrrolidines 11 ... 

The use of an optically active RBC12 gave secondary amines of essentially 100% optical purity.363 In other methods, trialkylboranes R3B gave secondary amines RR NH upon treatment with N-chloroamines R NHCl,364 and aryllead triacetates ArPb(OAc)3 give secondary amines ArNHAr when treated with primary aromatic amines Ar NH2 and Cu(OAc)2. s An indirect method for the conversion of aldehydes to N,N-disubstituted amides is based on the conversion of an 0-(trimethylsilyl)aldehyde cyanohydrin 34 to the amine 35.366... 

The groups R2N and Cl can be added directly to olefins, allenes, conjugated dienes, and alkynes, by treatment with dialkyl-N-chloroamines and acids.663 These are free-radical additions, with initial attack by the R2NH + radical ion,664 N-Halo amides RCONHX add RCONH and X to double bonds under the influence of uv light or chromous chloride.665 For an indirect way of adding NH2 and I to a double bond, see 5-32. 

Primary or secondary amines react with sodium or calcium hypochlorites to give N-chloroamines, some of which are explosive when isolated. Application of other chlorinating agents to amines or their precursors may also produce the same result under appropriate conditions. 

The MINDO calculations 141> (Table 7) reproduce satisfactorily the experimental barriers with respect to barrier heights as well as to observed trends. The barrier increase observed in hydrazines and N-chloroamines with respect to the corresponding amines has been attributed to lone pair-lone pair repulsions. 

Chloroacetaldehyde oxime, 2-carbon cyclization using, 55, 287 N-Chloroamides, chlorinating agents for pyrroles, 57, 326 N-Chloroamines radical cyclizations from, 58, 19 radicals by photolysis of, 58, 10 Chlorocarbonylsulfenyl chloride, reaction with 5-aminouracils, 55, 153 Chlorodimethylsulfonium chloride,... 

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