Hypochlorite rearrangement

On attempted vacuum-distillation of the 1-methylcyclopentyl hypochlorite obtained by chlorination of 1-methylcyclopentanol in alkaline solution, Cairns and Englund116 observed quantitative rearrangement of this material to 6-chloro-2-hexanone  

This reaction opens a route to co-halo ketones that are otherwise difficultly accessible. It has been recognized as a radical chain reaction.117 

Migration from carbon to nitrogen 1. Hofmann amide degradation118 

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V-Chloropyrrole, prepared from pyrrole and aqueous sodium hypochlorite, rearranges in methanol to a mixture of 2- and 3-chloropyrroles 2,5-dichloropyrrole is also formed/ Anodic oxidation of 1,2,5-trimethylpyrrole in the presence of cyanide ions yields the pyrroline (110) as the primary... 

If a bromomethyl- or vinyl-substituted cyclopropane carbon atom bears a hydroxy group, the homoallyiic rearrangement leads preferentially to cyclobutanone derivatives (J. Sa-laun, 1974). Addition of amines to cydopropanone (N. J. Turro, 1966) yields S-lactams after successive treatment with tert-butyl hypochlorite and silver(I) salts (H.H. Wasserman, 1975). For intramolecular cyclopropane formation see section 1.16. 

When position 4 of perfluoropyridine is blocked with a poor leaving group, ammonia replaces the fluonne in position 2 in good yield. Oxidation of the products obtained with hypochlorite, followed by lodme-catalyzed rearrangement, yields interesting fluorodienes [78] (equation 41) Ultraviolet irradiation can be used to assist reactions m which substitution is difficult [79]... 

The sulfur analogue of the Hauser ortho-substitution rearrangement provides access to an arylacet-ic NSAID. Reaction of the aminobenzophenone 176 with ethyl methylthioacetate and tert-butyl hypochlorite gives the intermediate 178. The reaction probably proceeds by way of formation of the S-chlorinated sulfonium derivative 177 displacement on sulfur will lead to the salt 178. Treatment with triethylamine leads initially to the betaine 179. Electrocyelic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid 180. Internal ester-amine interchange leads then to indolone 181 [45]. The thiomethyl group is then removed with Raney niekel. Saponifieation of intermediate 182 affords bromfenac (183) [46J. 

Treatment with sodium hypochlorite or hypobromite converts primary amines into N-halo- or N,N-dihaloamines. Secondary amines can be converted to N-halo secondary amines. Similar reactions can be carried out on unsubstituted and N-substituted amides and on sulfonamides. With unsubstituted amides the N-halo-gen product is seldom isolated but usually rearranges (see 18-13) however, N-halo-N-alkyl amides and N-halo imides are quite stable. The important reagent NBS is made in this manner. N-Halogenation has also been accomplished with other reagents, (e.g., sodium bromite NaBr02) benzyltrimethylammonium tribromide (PhCH2NMe3 Br3"), and NCS. The mechanisms of these reactions involve attack by a positive halogen and are probably similar to those of 12-47 and 12-49.N-Fluorination can be accomplished by direct treatment of amines °° or... 

Presumably the active chlorine of the chloramines formed by reaction with chlorine gas or hypochlorite reacts with TDM in the presence of acetic acid to yield dark blue, mesomerically stabilized quinoid reaction products that possibly rearrange to yield triphenylmethane dyestuffs. 

The Hoffman rearrangement of amides by quaternary ammonium hypochlorites is not particularly efficient under phase-transfer catalytic conditions and only low yields of nitrile, aldehydes, or ketones, which result from oxidation of the amines, are... 

Dichlorination was also observed when two molar equivalents of NCS or /-butyl hypochlorite reacted with 1-hydroxypyrazoles and their 2-oxides. One equivalent of NCS gave only the 4-monochloro derivative in high yield (80JOC76). When there was already a 4-substituent present, as with 3,4,5-trisubstituted pyrazole 2-oxides or 1-hydroxy-3,4,5-trisubsti-tuted pyrazole 2-oxides, the reaction products were 4-chloro-4// derivatives (77JOC3721). With 2 mol of /-butyl hypochlorite, 3,5-diphenylpyra-zole gave the unstable 1,4-dichloro derivative, which rearranged to form... 

The final, critical oxidative spirocyclization of the 2,3-disubstituted indole to the spiro oxindole was effected by treatment of 124 with tert-butyl hypochlorite in pyridine to provide the labile 125 [Fig. (34)]. The Pinacol-type rearrangement was conducted by treating compound 125 with p-toluenesulfonic acid in THF/water. It is assumed that the chlorination of 124 proceeds from the least hindered face of the indole, to give the a-chloroindolene 125. The hydration of the imine functionality must also occur from the same a-face that is syn to the relatively large chlorine atom furnishing the syn-chlorohydrin 126, that subsequently rearranges stereospecifically to the desired spiro oxindole 127. 

Until recently, in the chemistry of hypochlorites, there has been particular emphasis on the chemistry of -butyl hypochlorite. Hypochlorites in general were ignored. However, in their classical paper on the photolysis of organic nitrites,48 Barton et al. adumbrated a photochemical rearrangement of hypohalites of the type (A) —> (B) (X = any halogen). A year later applications of this principle were described... 

In the steroid series photochemical rearrangement of hypochlorites of the type A - B (X = halogen) were first used successfully at the Institute to functionalize the 18- and 19-methyl groups.51-63 Thus the hypochlorite (5) on irradiation gave the corresponding chlorohydrin which was smoothly cyclized to the ether (6, X = H2) oxidation of the ether to the lactone (6, X = O) constituted a formal proof of its structure. 

The orf/to-formylation of 2-aminopyridines can be effected via the rearrangement of the azasulfonium salt prepared from a 2-aminopyridine, 1,3-dithiane, f-butyl hypochlorite and sodium methoxide (74CC685). The crude sulfilimine (815) was refluxed in f-butanol containing potassium f-butoxide to yield the dithioacetal (816). Hydrolysis of (816) with mercury(II) oxide/boron trifluoride etherate gave the aldehyde (817 Scheme 191). This method should be applicable to the formylation of other heterocyclic amines. 

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