Ketones and aldehydes halogenation

The possibility of hydrogenating halogenated aldehydes and ketones by means of phytochemical reduction was tested as early as 1913 the successful results in this field clearly demonstrate the importance of this method. Lintner and Ltters found that chloral hydrate can be converted to trichloroethyl alcohol. This transformation takes place so easily that, according to Willstatter and Duisberg, it can be used under favorable experimental conditions as a convenient method for the preparation of the halogenated alcohol. The tribromoethyl alcohol may be prepared in an analogous manner. 

As seen in Table 13.7, oxidation of HCFCs by OH generates a variety of halogenated aldehydes and ketones as well as phosgene (COCl2), its fluorine analog (COF2), C1C(0)F and HC(0)F, and the alcohol CF3OH. The ultimate atmospheric fate of these products depends on their structures, of course, which determines their absorption cross sections as well as reactivity with OH, and their solubility in aqueous solutions such as clouds, rainwater, and the oceans. 

The facile reaction of CAA and BAA with nucleosides and nucleotides is one example of many of the applications of the bifunctional reactivity of halogenated aldehydes and ketones in modification of biomolecules. In an early example of the extensive use of halogenated ketones as protease substrate analogues, l-V-tosylamido-2-phenylethyl chloro-methyl ketone (TPCK) 30 was synthesized as a chymotrypsin substrate analogue. Stoichiometric inhibition was accompanied by loss of one histidine residue as a result of alkylation by the chloromethyl moiety68. A host of similar analogues were subsequently prepared and used as selective enzyme inhibitors, in particular for the identification of amino acid residues located at enzyme active sites69. 

AUphatic halogenated aldehydes and ketones. In general these compounds react normally with the usual reagents for the carbonyl group (but see also pages 93,94). 

This section examines a reaction of the carbonyl gronp that can proceed through the intermediacy of either enols or enolate ions—halogenation. Aldehydes and ketones react with halogens at the a-carbon. In contrast with deuteration, which proceeds to completion with either acid or base, the extent of halogenation depends on whether acid or base catalysis has been nsed. 

Other than nucleophilic addition to the carbonyl group the most important reac tions of aldehydes and ketones involve replacing an a hydrogen A particularly well stud led example is halogenation of aldehydes and ketones... 

Aldehydes and ketones react with halogens by substitution of one of the a hydrogens... 

As m the acid catalyzed halogenation of aldehydes and ketones the reaction rate is mde pendent of the concentration of the halogen chlorination brommation and lodmation all occur at the same rate Formation of the enolate is rate determining and once formed the enolate ion reacts rapidly with the halogen... 

Esterification of carboxylic acids involves nucleophilic addition to the carbonyl group as a key step In this respect the carbonyl group of a carboxylic acid resembles that of an aldehyde or a ketone Do carboxylic acids resemble aldehydes and ketones m other ways Do they for example form enols and can they be halogenated at their a carbon atom via an enol m the way that aldehydes and ketones can ... 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

OL Halogenation (Sections 18.2 and 18.3) Halogens react with aldehydes and ketones by substitution an a hydrogen is replaced by a halogen. Reaction occurs by electrophilic attack of the halogen on the carbon-carbon double bond of the enol form of the aldehyde or ketone. An acid catalyst increases the rate of enolization, which is the ratedetermining step. 

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. 

As an example of enolate-ion reactivity, aldehydes and ketones undergo base-promoted o halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it s not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen, removing it from the reaction and driving the equilibrium for further enolate ion formation. 

Reactions 11-22-11-26 involve the introduction of a CH2Z group, where Z is halogen, hydroxyl, amino, or alkylthio. They are all FriedeI-Crafts reactions of aldehydes and ketones and, with respect to the carbonyl compound, additions to the C=0 double bond. They follow mechanisms discussed in Chapter 16. 

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