Chlorination of a ketone

Selected examples of the mono-a-chlorination of methyl ketones... 

The C=C bond in a 5-(alkylidene)oxazoline 644 is activated for electrophilic reactions similar to that in analogous vinyl acetates. Rohm Haas researchers exploited this property to prepare chloromethyl ketone fungicides 646 (Scheme 8.203). The overall process constitutes an indirect chlorination of a-amido ketones since the 5-(vinylidene)oxazolines were prepared from a-amido ketones. 

The chlorination of a,/i-unsaturated ketones by CI2 in MeOH gives mixtures of Markovnikov and anti-Markovnikov methoxychlorides and dichlorides. Significant increase in the proportion of Markovnikov regioisomers was observed in the presence of acid scavengers, such as pyridine. This effect was ascribed to the elimination of the acid-catalysed mechanism, allowing the chlorination to occur via chloronium ion174. 

In the early twentieth century Leuchs reported a surprising example of the a-chlorination of chiral ketone 73, which gave optically active 74 in the absence of additional chiral sources.36 From a mechanistic point of view, however, there remains some ambiguity. Possible mechanisms for the formation of optically active 74 include (1) asymmetric chlorination via an enol intermediate (i.e., memory of chirality), (2) direct electrophilic chlorination of the C-H bond at the stereogenic carbon center, (3) complex formation of an achiral enol intermediate with optically active 73, (4) resolution of dl-74 by co-crystallization with optically active 73, and (5) simultaneous resolution of dl-74. 

Chlorination of steroid ketones has been studied in only a few cases. The reaction with elementary chlorine [iS ] is generally similar to bromination, but other sources of electrophilic chlorine have also been used. These include sulphuryl chloride, pyridine hydrochloride perchloride, and tert-butyl hypochlorite [J57]. 

Phase-transfer addition (c/. Vol. 6, p. 31) of dibromocarbene to carvone and reduction to a monobromo-ketone by tributyltin hydride, or to a dibromo-alcohol with lithium aluminium hydride, is reported/ 1,3-Dipolar cycloaddition of acetonitrile oxide occurs exclusively at the exocyclic double bond in limonene to give (155 R = Me, X = Hi), whereas isoxazoline formation with carvone yields (155 R = Me, X —O) and the isomeric product from attack at the C-6 double bond benzonitrile oxide, however, only yields (155 R = Ph, X = 0 or NOH). A re-investigation of aqueous chlorination of a -terpineol indicates that the diequator-ial chlorohydrin (156) and the corresponding diaxial chlorohydrin are the major... 

For most uses, hydrazine is produced as hydrazine hydrate in a formulation with water. The hydrate may be produced commercially by three methods the Raschig process, the ketazine process, and the peroxide process. The Raschig process, the original commercial production process for hydrazine, involves oxidation of ammonia to chloramine with sodium hypochlorite, then further reaction of the chloramine with excess ammonia and sodium hydroxide to produce an aqueous solution of hydrazine with sodium chloride as a by-product. Fractional distillation of the product yields hydrazine hydrate solutions. Currently, most hydrazine is produced by the ketazine process, which is a variation of the Raschig process. Ammonia is oxidized by chlorine or chloramine in the presence of an aliphatic ketone, usually acetone. The resulting ketazine is then hydrolyzed to hydrazine. In the peroxide process, hydrogen peroxide is used to oxidize ammonia in the presence of a ketone. Anhydrous hydrazine is the formulation used in rocket fuels and is produced by dehydration of the hydrate by azeotropic distillation with aniline as an auxiliary fluid (Budavari et al. 1989 lARC 1974 Schmidt 1988 WHO 1987). 

Observed changes in the reaction order in the presence of chloride ion show that it takes part in the formation of other halogenating agents by a reaction with CBT. The workers (82PIA921) consider that in this case a complex C is formed between protonated CBT and the chloride ion. This complex contributes the chlorination of the enolic form of a ketone (Scheme 64). 

Both in the pyridazine,12-9 and in the pyridine23 moiety of the pyrido[2,3-c]pyridazine system conversions of a ketone or hydroxy group into a chloro substituent are known. As in the other pyridodiazine series, the reagent of choice is phosphoryl chloride, e.g. chlorination of 1 to give 2,9 12 or 3 to give 4.23... 

Halogenation of a- to Carbonyl Groups. Regioselective a-bromination or chlorination of unsymmetrical ketones at the more substituted -position has been demonstrated with trimethylsilyl halides in DMSO the halogenating species is presumed to be the... 

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