IV-Chloroamines

The free 17j8-amine can be transformed to the 17-ketone by chlorination to the iV-chloroamine, dehydrohalogenation to the imine, and finally hydrolysis.While these latter steps proceed in reasonable yield, the overall sequence does not compare well in efficiency with the process starting with a A -20-keto steroid ... 

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

Within the first pathway, reduction of the nitrile was facilitated by preliminary methylation with dimethylbromonium hexafluoroantimonate in liquid sulfur dioxide and subsequent methanolysis to the iminoether, which was treated with sodium cyanoborohydride (Scheme 20). The secondary amine 191 was chlorinated with sodium hypochlorite to the corresponding iV-chloroamine to enable titanium... 

The iV Chloroamine reaction (above) [2,3] is most efficient in the aoa-aminopregnane series (i), and gives a lower yield from the 20jl isomer (2). Inspection of models shows that the... 

Steroidal primary amines have been transformed into the corresponding ketones by the action of hypochlorite and aqueous alkali. The reaction is probably analogous to the oxidation of secondary alcohols by hypohalite (p. 34) an intermediate iV-chloroamine (i) undergoes base-catalysed elimination to give the imine 2) which is hydrolysed by the aqueous medium to give the ketone. The process is illustrated for a 17 -aminoandrostane, derived by Beckmann rearrangement of the oxime of a 20-oxopregnane derivative [31]. 

Table 2. Homolytic amination of aromatic compounds with protonated iV-chloroamines...

Following upon closely related earlier work, it has been found that photolysis of the iV-chloroamine (3) leads to loss of the piperidine ring as 5-methyl-A -piperideine and formation of the C-20 diastereoisomeric derivatives (4). 

Synthesis of Al-Chloroamines. The conversion of secondary amines to iV-chloroamines by reaction with NCS in ether or dichloromethane has many advantages over the use of aqueous hypochlorite, including ease of isolation. This method has been used repeatedly in the preparation of Al-chloroamines for alkene amination (eqs 12 and 13) and other reactions. ... 

Fatty acids can be chlorinated with fair to good selectivity at the co to (co — 3) positions by electrostatic orientation or partial shielding. In the first case the acid is chlorinated with iV,N-dialkyl-iV-chloroamine in strong acid . In the second case the acid is adsorbed at alumina and chlorinated at the gas-solid interphase. ... 

Because of the availability of the starting materials, the high selectivity and the high yields observed, the mild conditions employed, and the fact that high-dilution conditions are not needed, the scope of the titanous chloride reduction of unsaturated IV-chloroamines has been rather extensively studied. Some other examples of cyclization are recorded in this section as well as in Section XI. 

This, for instance, may be why no cyclized products have been obtained from acetylenic iV-chloroamines under the free radical conditions discussed in Section whereas aminyl radicals easily added intramolecularly to... 

That attack on an aromatic ring is less favored than attack on a double bond is confirmed by the behavior of iV-chloroamine 81 (X = CH2) (Section VIII.3.A, Scheme 43). Only the monocyclized compound 82 is obtained... 

Scheme 10.16. The formation of 1,2-dimethylazacyclopentane (1,2-dimethylpyrroUdme) by radical cleavage and loss of HCl from the corresponding iV-chloroamine.

More recent reports in 2012 and 2013 focus on the use of more sustainable metals such as iron in these cases an oxidant is required. Two equivalents of tert-butyl hydroperoxide (TBHP) for example were used with 2.5 mol% FeCla. In times as short as 1 h, in acetonitrile at 85 °C, various aliphatic and aromatic aldehydes were able to be oxidatively amidated to the corresponding amides with a range of secondary and tertiary amines. Similar work has been done by De Luca and co-workers using TBHP as an oxidant in combination with either an FeCls or Cu(OAc)2 catalyst. However, in both cases, iV-chloroamines had to be formed in situ in order to generate the required amino radical coupling partner. 

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