Ketones, reaction with bromine

A"" -3-Ketones are more reactive than cross-conjugated A ""-3-ketones. A"" -3,3-CycIoethylenedioxy compounds can be easily prepared by acid-catalyzed reaction with ethylene glycol or by exchange dioxolanation. 3,3-Cycloethylenedioxy-A -dienes can be prepared from 3,3-cycloethy-lenedioxy-A -enes by allylic bromination and dehydrobromination. Acid hydrolysis yields A"" -3-ketosteroids. ... 

Ai -A-homo-4-ketones by reaction with lithium and biphenyl at The resulting dienone is transformed into the corresponding tropone by treatment with bromine. The Swiss chemists also found that base treatment of 19-mesyloxy-A " -3-oximes gives directly 4-oximino-A-homo-estra-l(10),2,4a-trienes in moderate yield. ... 

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

The benzylic position of an alkylbcnzene can be brominated by reaction with jV-bromosuccinimide, and the entire side chain can be degraded to a carboxyl group by oxidation with aqueous KMnCfy Although aromatic rings are less reactive than isolated alkene double bonds, they can be reduced to cyclohexanes by hydrogenation over a platinum or rhodium catalyst. In addition, aryl alkyl ketones are reduced to alkylbenzenes by hydrogenation over a platinum catalyst. 

A particularly common cr-substitution reaction in the laboratory is the halogenation of aldehydes and ketones at their a- positions by reaction with Cl2, Br2, or I2 in acidic solution. Bromine in acetic acid solvent is often used. 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

Allylmagnesium bromide, 41, 49 reaction with acrolein, 41, 49 5-Allyl-l,2,3,4,5-pentachlorocyclopen-tadiene, 43, 92 Allyltriphenyltin, 41, 31 reaction with phenyllithium, 41, 30 Aluminum chloride, as catalyst, for isomerization, 42, 9 for nuclear bromination and chlorination of aromatic aldehydes and ketones, 40, 9 as Friedel-Crafts catalyst, 41, 1 Amidation, of aniline with maleic anhydride, 41, 93... 

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 ... 

The reaction with bromine is very rapid and is easily carried out at room temperature, although the reaction is reversible under some conditions. In the case of bromine, an alkene-Br2 complex has been detected in at least one case. Bromine is often used as a test, qualitative or quantitative, for unsaturation. The vast majority of double bonds can be successfully brominated. Even when aldehyde, ketone, amine, so on functions are present in the molecule, they do not interfere, since the reaction with double bonds is faster. 

Primary, secondary, and tertiary aliphatic amines have been cleaved to give aldehydes, ketones, or carboxylic acids with aqueous bromine and with neutral permanganate. The other product of this reaction is the amine with one less alkyl group. In a different type of procedure, primary alkyl primary amines can be converted to ge/n-dihalides, RCH2NH2 —> RCHX2 (X =Br or Cl), by treatment with an alkyl nitrite and the anhydrous copper(I) halide. 

Although the reaction of ketones and other carbonyl compounds with electrophiles such as bromine leads to substitution rather than addition, the mechanism of the reaction is closely related to electrophilic additions to alkenes. An enol, enolate, or enolate equivalent derived from the carbonyl compound is the nucleophile, and the electrophilic attack by the halogen is analogous to that on alkenes. The reaction is completed by restoration of the carbonyl bond, rather than by addition of a nucleophile. The acid- and base-catalyzed halogenation of ketones, which is discussed briefly in Section 6.4 of Part A, provide the most-studied examples of the reaction from a mechanistic perspective. 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

With ketones such as (94), that have alternative groups of a-H atoms to attack, two questions arise (a) which group, the CH2 or the CH3, is attacked preferentially, and (b) when one H has been substituted by halogen, will a second halogen become attached to the same or to the other a-carbon atom. So far as (a) is concerned, it is found that bromination of, for example, MeCH2COCH3, yields 1- and 3-bromobutanones in virtually equal amount (both these bromoketones then undergo very rapid further reaction, cf. p. 296). The inductive effect exerted by a simple alkyl group, R, thus appears to have relatively little effect on the acidity of H, or on the... 

In this respect such reactions are analogous to the S 1 or limiting reactions of compounds producing carbonium ions, although the intermediate is a solvated carbanion rather than a solvated carbonium ion. In the base-catalyzed halogenation of ketones, for example, the rate is independent of the halogen concentration and is the same for the reaction with bromine as for the reaction with chlorine.384... 

The proof is based on the fact that the reaction between acetone and bromine is recognised as being unimolecular and not, as would be expected, bimolecular. In the determination of the velocity of reaction, therefore, the (slow) conversion of the ketone into the enol is measured, whilst the addition of the bromine occurs with immeasurable rapidity. 

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