Bromination methyl ketone

Methyl ketones 1, as well as acetaldehyde, are cleaved into a carboxylate anion 2 and a trihalomethane 3 (a haloform) by the Haloform reaction The respective halogen can be chlorine, bromine or iodine. 

The regiospecificity of bromination depends on the structure of the ketone.7 This regiospecificity is very high for methyl ketones when the a -position is tertiary, and not as high when it is secondary. For example,... 

In the haloform reaction, methyl ketones (and the only methyl aldehyde, acetaldehyde) are cleaved with halogen and a base. The halogen can be bromine, chlorine, or iodine. What takes place is actually a combination of two reactions. The first is an example of 12-4, in which, under the basic conditions employed, the methyl group is trihalogenated. Then the resulting trihalo ketone is attacked by hydroxide ion ... 

Phenyl methyl ketone 1 was brominated to give l-phenyl-2-bromoethanone 2. Compound 2 was treated with methylsulfonic acid to yield the corresponding methylsulfonate 3. Etherification of 3 gave the a-benzyloxy derivative 4 and compound 4 was then chlorinated to give the 2,4-dichlorinated derivatives in both aromatic ring systems 5. Compound 5 reacted with imidazole in dimethylformamide to give miconazole 6 [7], which is converted to miconazole nitrate. 

Since it does not reduce Tokens or Fehltng reagent, (A) must be a ketone. (A) responds to iodoform test. Therefore, it should be a methyl ketone. The molecular formula of (A) Indicates high degree of unsaturation, yet it does not decolourise bromine water or Baeyer s reagent. This indicates the presence of unsaturation due to an aromatic ring. 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

The synthetic utility of many of the substitution reactions described so far is limited because there are well-established thermal routes to the same products. However, a third group of photochemical nucleophilic substitutions involves aryl halides and nucleophiles based on sulfur, phosphorus or, of particular importance, carbon. Two examples are the reaction of bromobenzene with the anion of t-butyl methyl ketone 13.12), and the replacement of bromine by cyanomethyl in 2-bromopyridine (3.13). This type of reaction offers a clear advantage over lengthy thermal alternatives, and intramolecular versions have been used in the synthesis of indoles (e.g. 3.14) or benzofurans from o-iodoaniline or o-iodoanisole respectively. 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

Since the methyl group of TNT is attached to a picryl group, we should expect it in some respects to resemble the methyl group of a ketone. Although acetone and other methyl ketones bromi-nate with great ease, TNT does not brominate and may even be recrystallized from bromine. The methyl group of TNT, however, behaves like the methyl group of acetone in certain condensation reactions. In the presence of sodium carbonate TNT condenses with p-nitrosodimethylaniline to form the dimethylaminoanilide of trinitrobenzaldehyde,33 from which trinitrobenzaldehyde and N,N-dimethyl-p-diaminobenzene are produced readily by acid hydrolysis. 

Bromination of the methyl group can be restricted to monosubstitution when the reaction is carried out in acidic media. The mechanism involves protonation of the carbonyl-oxygen, followed by proton loss to give the enol. After monobromination, protonation of the bromoketone is less favourable owing to the presence of the electron-withdrawing halogen atom. Further enolisation does not occur therefore and halogenation ceases (contrast the behaviour of methyl ketones on bromination under alkaline conditions, p. 667) the product is an aryl bromomethyl ketone or phenacyl bromide. 

Y-Chlorosaccharine748 and also TCCA749 are useful reagents for the chlorination of ketones. The regioselectivity in the electrophilic bromination of methyl ketones is strongly influenced by the presence of amides. Normally, the a-methylene group is brominated but, upon addition of urea, up to 80% of a-methyl bromination is obtained750. 

Propose a mechanism for the reaction of cyclohexyl methyl ketone with excess bromine in the presence of sodium hydroxide. 

Interaction of hydrogen iodide and diazoketones forms methyl ketones with the liberation of nitrogen and iodine (method 228). If the diazoketone is treated with bromine, then a dibromomethyl ketone, RCOCHBtj, is formed, ... 

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