A -Chloroamines

A-Bromo- as well as A-chloroamines have been used as starting materials. For practical reasons (greater stability) the easily accessible A-chloro compounds are preferred. 

Carbomethoxymethylenetriphenylphos-phorane, 129 Carbon radicals, 240 Carbonyl-forming fragmentations, 239 2a-Carboxy-A-nor-5a-cholestane, 427 Caro s acid, 152 Chlorineazide, 25, 34, 35 Chloro c lene, 136, 138 A-chloroamine reactions, 257 5a-Chloro-6 -azidocholestan-3/3-ol, 25... 

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

Another variation of the Hofmann-Loffler-Freytag reaction involves sulfonamides in place of A-chloroamines. For instance, in the presence of NaaSaOg and CuCb, butylsulfonamide (17) was transformed to 4-chlorobutylsulfonamide (18) and 3-chlorobutylsulfonamide (18) in the absence of an acid. ... 

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. 

The required A-chloroamines 9 can be prepared from the corresponding amine by treatment with sodium hypochlorite or A-chlorosuccinimide. 

Thus, the following reaction led to a chloroamine, which was stored at 20°C and detonated three months after being prepared ... 

An Arbuzov reaction of triethyl phosphite with A-chloroamines RNHC1 (R = i-Pr, cyclohexyl or PhCH2), prepared from the corresponding amines and aqueous sodium hypochlorite, leads to the phosphoramides 357 with the elimination of ethyl chloride395. 

Preliminary studies of nitrogen substituent inversion processes have been reported for several naphthalen-l,4-imine derivatives. The syn and anti invertomers of the A-chloroamine (117) equilibrate in solution to a mixture in proportion 3 2. The process can be followed kinetically by NMR spectroscopy starting from the pure anti compound the inversion is relatively slow ki = 2.6 x 10 sec at 23°), and the free-energy barrier to inversion is as high AF = 23.5 kcal mole ) as values found for inversion in aziridines. (A-Chloroaziridine derivatives, for which the energy barrier is even higher, have also been resolved into diastereoisomeric invertomers. )... 

Dioxazolidines are produced by cyclization of A,A-dialkoxy- or A -alkoxy-A -chloroamines (Scheme 11) <93CRV725>. The synthetic potential of this method far surpasses that of the photochemical addition of nitrobenzene to alkenes <84CHEC-1(6)-914). 

Other evidence advanced in favor of alkyl nitrenium ions came from Ag+ promoted isomerization and solvolysis of various cyclic and bicyclic A-chloroamines (e.g., A representative example is shown in Figure 13.12. It was argued... 

Figure 13.25. Nitrenium ions through heterolysis of A -chloroamines.

Davidse et al. " described the photolysis of A-chloroamine and hydroxylamine esters (55) to form nitrenium ions by heterolysis (Fig. 13.33). As noted above, these reactants also yield nitrenium ions through thermal chemistry, albeit more slowly. 

II. Functionalization of the Angular Methyl Groups / 237 General principles of substitution / 237 Lead tetraacetate oxidations / 240 Hypohalite reactions / 246 Photolysis of nitrites (Barton reaction) / 253 A-Chloroamine reactions (Hoffmann-Lofller reaction) / 257 Ketone irradiations / 260 Summary / 264... 

The synthesis of pyrrolidines by the free radical transformation of A-chloroamines, the HofmannLoefflerFreytag reaction, is of preparative significance. A typical example is shown in Scheme 33 <1959JOC572>. 

A study of the decomposition of ) -hydroxy-A-chloroamines in aqueous medium has established that pre-equilibrium formation of the conjugate alcoholate is a prerequisite feature of the competing fragmentation and intramolecular elimination paths (Scheme 13). A very high effective molarity (EM — 2 x 10 M) has been estimated for the intramolecular process, which cannot occur in the case of (7V-chloro)butylethanolamine. For reaction of (7V-chloro)ethylethanolamine kjntra/ ftag = 6.1 and the solvent isotope effect (koH-/ OD-)obs — 0-68 is consistent with pre-equilibrium deprotonation followed by a imimolecular reaction in which there is no participation by solvent. 

This type of transformation has been employed for the synthesis of several different nitrogen heterocycles [98], and an analogous reaction of unsaturated A-chloroamines that generates pyrrolidine products has also been described [99]. 

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

Homolytic aromatic amination with electrophilic dialkyl aminyl radical cations is a valuable method for the preparation of aniline derivatives [2e, 10a]. The radical cations (R2HN+ ) are generally prepared from the corresponding A-chloroamines... 

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