Unsaturated ketones halogenation

The halogenation-dehydrohalogenation of ketones and their derivatives is the most widely applied method for the preparation of unsaturated ketones, and the different combinations of alternatives which exist for both steps extend the scope of this approach. Consequently, this route will be discussed in considerable detail. 

Bromination with A-bromosuccinimide generally gives the same result as bromination with free bromine or hypobromous acid. The reaction is considered to proceed with a small concentration of free bromine and does not generate an appreciable concentration of acid. Conditions are therefore mild. In addition, A-bromosuccinimide has been used to brominate the allylic position of a, -unsaturated ketones in the presence of free-radical promoters or with irradiation, and thus gives access to dienones by dehydro-halogenation, for exaraple " ... 

Halogenation of the double bond usually prevents the satisfactory preparation of vinylogous a-halo ketones by direct reaction of unsaturated ketones with... 

Halogenated- ,/S-unsaturated ketones or aldehydes are reacted with methyl thioglycolate and cyclized with alkali alcoholate/ Thus jS-bromobenzalacetone (75) gives methyl 3-methyl-5-phenyl-2-thio-phenecarboxylate (76) and from a-methyl-j5-chlorocrotonaldehyde (77), 4,5-dimethyl-2-thiophenecarboxylate (78) is obtained. 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

Because the haloform reaction is fast, in some cases it can be used to prepare unsaturated acids from unsaturated ketones without serious complications caused by addition of halogen to the double bond ... 

Table V is also an index to Table I it classifies the compounds according to the functional groups they contain. One frequently wants to examine data on carbonyl compounds, on unsaturated or halogenated ketones, or another more or less specific class of substances, and the purpose of Table V is to simplify searches of this sort. Pyruvic acid appears in Table V both among the ketones and among the carboxylic acids, and Inspection of either group would quickly reveal any closely related compound that appears in this volume.

However, acylation reactions of N-unsubstituted pyrazolines with halogen anhydrides of acids are very often followed by the destruction of the heterocyclic ring owing to the ease of breaking the C(5)—Nq) bond located at the (3-position of the azomethine group [140, 141, 142, 166]. For example, pyrazoline 108 treated with halogen anhydrides of acids yields a,(3-unsaturated ketone 109 and diacyl-hydrazine 110 [166] (Scheme 2.29). 

Ether Formation. It is reported that the reduction products of certain a,j8-unsaturated ketones, for example, dibenzalacetone (XL), contained sonfe of the isopropyl ethers pf the carbinols.6 Carbinols of this type are especially susceptible to ether formation often recrystallization from an alcohol is sufficient to give the ether. However, ether formation is by no means the usual reaction with unsaturated ketones. Indeed, in most cases no ether was noted in the products. Even in the case of dibenzalacetone, the normal product, i.e., the carbinol, has been obtained in 58% yield.36 9,9-Dimethylanthrone-10 (XLI) gave 64% of a material corresponding in analysis to the isopropyl ether (XLII).17 Similar observations of ether formation with a-halogen ketones will be discussed later. There appears to be no way of predicting with any degree of certainty when ether formation is likely, but it is not a common side reaction. 

The synthetic utility of the Favorskii rearrangement is somewhat reduced by side-reactions including substitution of the halogen atom, elimination to form unsaturated ketones and epoxide formation. However, if the starting ketone is polyhalogenated, then... 

Acid-catalyzed halogenation is synthetically useful for converting ketones to a,/3-unsaturated ketones, which are useful in Michael reactions (Section 22-18). Propose a method for converting cyclohexanone to cyclohex-2-en-l-one, an important synthetic starting material. 

Chlorine and bromine have been added on to the double bonds of some a, -unsaturated ketones, especially A - (27) and A 3-ketones (28 [1x2,xx ]. The products have the usual r s-diaxial configuration of halogens, but it is not possible to... 

Halo-ajS-unsaturated ketones and esters are highly susceptible to 8 2 displacement at the carbon attached to halogen, so strong bases are undesirable for such substrates [60, 91, 92]. However, relatively weak bases, such as sodium acetate and even triethylamine, are effective when the reaction is conducted in alcohol solvents [60]. Sodium acetate suspended in methanol, and aqueous or solid carbonate in ethanol give best results for haloenones (Scheme 2-33) [60] and haloesters [91], respectively. 

---