Trihalomethyl ketone

The trihalomethyl ketone (RCCX3) so formed then undergoes nucleophilic addition of hydroxide ion to its carbonyl group triggering its dissociation... 

Trihalomethyl ketones react with alcohols ia the presence of alkaline catalysts even at room temperature (94) ... 

The methyl group of a methyl ketone is converted into an a ,a ,a -trihalomethyl group by three subsequent analogous halogenation steps, that involve formation of an intermediate enolate anion (4-6) by deprotonation in alkaline solution, and introduction of one halogen atom in each step by reaction with the halogen. A... 

Methyl ketones are degraded to the next lower carboxylic acid by reaction with hypochlorite or hypobromite ions. The initial step in these reactions involves base-catalyzed halogenation. The a-haloketones are more reactive than their precursors, and rapid halogenation to the trihalo compound results. Trihalomethyl ketones are susceptible to alkaline cleavage because of the inductive stabilization provided by the halogen atoms. 

A possible mechanism that features a six-membered transition state is given in Scheme 18 (38, 43). The high catalytic activity stems from the excess strain of the B=N bond in the 5/5-fused bicyclic ring system, which results in strong coordination of the angular nitrogen atom to BH3 to form the active dinuclear species. The rate and stereoselectivities of the reaction of trihalomethyl ketones has been explained on the basis of the X-ray analysis of the substrates. 

Acylphosphonates, e.g. (5), possess highly reactive carbonyl groups and—somewhat like trihalomethyl ketones—exhibit both ketone and carboxy character, forming oximes and adducts, and also carboxylate derivatives via C—P bond cleavage.7 Their hemiacetal derivatives have been studied by 31P-NMR in the presence of alcohols, for the representative acetyl and benzoyl compounds (5 R = Me, Ph). Equilibrium and... 

The oxidation of a methyl ketone to a carboxylic acid can be effected by the use of the haloform reaction. This involves treatment of the methyl ketone with an alkaline hypohalite reagent. A trihalomethyl ketone is initially formed which then undergoes hydrolysis under the basic conditions used. 

The catalyzed reduction has a wide scope for various ketones with excellent enantioselectivity (Table 6). The protocol was successfully applied to the reduction of a-siloxy and tetahydropyranyloxy ketones (entry l),1074 cr-bromo and cr-chloroacetophenne (entry 2),1091-1094 trihalomethyl ketones (entry 3),1095-1099 a-sulfonyl ketones (entry 4),1100... 

With most ketones, base-promoted halogenation continues until the a carbon atom is completely halogenated. Methyl ketones have three a protons on the methyl carbon, and they undergo halogenation three times to give trihalomethyl ketones. 

The haloform reaction (Problem 22.23d) is an alpha-substitution reaction in which a methyl ketone is trihalogenated at the alpha position, and the trihalomethyl group is displaced by -OH. It is a test for methyl ketones. 

Difluoroalkyl Fluoridothiocarhonates from a-(Trihalomethyl)sulfanyI Ketones... 

In the reaction of a-(trihalomethyl)sulfanyl ketones with hydrogen fluoride, /f,/f-difluoroalkyl fluoridothiocarhonates 14 are obtained instead of the expected trifluoromethyl sulfides.246 The reaction is thought to proceed via an initial chlorine-fluorine exchange reaction followed by rearrangement into the /i-difluorinated product. 

A trihalo compound may be formed from the halogenation of a methyl ketone. The electron-withdrawing effect of the trihalomethyl group makes the carbonyl group very sensitive to nucleophilic addition. Consequently, in the presence of a mild base the trihalomethyl compound easily decomposes with the formation of chloroform, bromoform or iodoform, depending on the halogen. The other product of the haloform reaction is a carboxylic acid (Scheme 3.86). 

Trichloroacetamido)phenyl ketone.s 18 or their tribromo analogs are, in most cases, readily converted to the corresponding 4-substituted quinazolin-2(l//)-ones 19 by reaction with ammonia via loss of the trihalomethyl function. Under similar conditions, the 2-trifluoroac-etamide derivative reacts to yield 2-(trifluoromethyl)quinazoline. The mechani.sm of this... 

The Seyferth s reagents (PhHgCX3) are particularly effective for the cyclopropanation of deactivated or base-sensitive substrates, such as allyl halides, allyl isocyanates, and polychloroalkenes (e.g. equation 64) as well as a,j5-unsaturated ketones, esters, nitriles, and sulfones The Michael addition of a trihalomethyl unit has not been observed in this... 

The mechanism of the haloform reaction has been extensively studied, and it can be concluded that it is a very complex process. The exact mechanistic pathway is dependent on the structure of the substrate and the specific reaction conditions. The scheme depicts the oxidation of a methyl carbinol to the corresponding methyl ketone via an organic hypohalite. The methyl ketone then undergoes deprotonation, and three sequential a-halogenations take place to afford the trihalomethyl ketone. This compound undergoes rapid hydrolysis to afford the haloform and a carboxylate. 

Alkali cleaves, a ,a>trihalomethyl ketones to trihalomethanes and carboxylic acids. This haloform reaction 714 also occurs directly if alkaline hypohalite solution is allowed to react with a methyl ketone and has preparative importance as a method of obtaining carboxylic acids from methyl ketones. 

In the presence of excess base and excess halogen, a methyl ketone is first converted into a trihalo-substituted ketone. Then hydroxide ion attacks the carbonyl carbon of the trihalo-substituted ketone. Because the trihalomethyl ion is a weaker base than hydroxide ion (the of CHI 3 is 14 the pK of H2O is 15.7), the trihalomethyl ion is the... 

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