Dehydrohalogenation of acyl halides

Pyrolysis of carboxylic acids Dehydrohalogenation of acyl halides Dehalogenation of a-halo acyl halides Rearrangement of diazo ketones (Wolff)... 

Dehydrohalogenation of Acyl Halides and Sulfonyl Halides Hydro-halo-elimination... 

An important method for the preparation of /3-keto esters is by the action of alcohols on ketene dimers in the presence of acid catalysts. Diketene and alcohols give acetoacetic esters in 60-80% yields. Dimers of higher ketenes are made by dehydrohalogenation of acyl halides and are converted to /S-keto esters in one operation (cf. method 245). 

Dehydrohalogenation of Acyl Halides by Means of Tertiary Amines.. . 124... 

Table VI. Preparation of Ketoketenes by Dehydrohalogenation of Acyl Halides. 126...

Dehydrohalogenation of Acyl Halides by Means of Tertiary Amines. 

The ketenes which have been prepared by dehydrohalogenation of acyl halides are listed in Table VI. 

Consequently, haloketenes can be readily generated in situ by two most widely used methods (a) the triethylamine dehydrohalogenation of an acyl halide (Eq. (3))50) (b) the dehalogenation of an a-haloacyl halide with activated zin (Eq. (4))51). Since the halogen substituents on the cyclobutanone can be reductively removed by usual procedures, the synthesis of a halocyclobutanone constitutes a formal preparation of the cyclobutanone, the synthetic utility of which is convincingly demonstrated by the following examples. 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

A variety of bases have been used to effect dehydrohalogenation of halo acids and halo esters. a-Bromo esters or a-bromo acyl halides give a,/3 lefinic acids with alcoholic potassium hydroxide. Yields are poor with the higher-molecular-weigbt a-bromo acids other products are those formed by substitution of the halogen atom by the basic anions. 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

Incorporation of a benzylic halide into the structure of the alternate-substrate lactone (12-4) led to the bifunctional lactones (13-1, Table 2.13), and (13-2), which showed rapid and irreversible inactivation of a-chymotrypsin and PPE [178]. It was postulated that the intermediate acyl-enzyme formed from attack of Ser-195 on the lactone carbonyl dehydrohalogenated to form a reactive quinone methide that coupled with His-57. If this mechanism were followed, then lactone (13-2) would be an example of a mechanism-activated inhibitor. However, lactone (13-2) is sufficiently reactive as an alkylating agent to directly couple with imidazole while the lactone ring is intact. Because of this, it is not clear, from the published data, whether acylation of Ser-195 precedes alkylation, a prerequisite for this compound to be confirmed as a mechanism-activated inhibitor. Interestingly, the corresponding coumarin (13-3) was both less potent and only provided partial inactivation of a-chymotrypsin [179, 180]. It was shown that the lactone linkage in this coumarin was stable in the presence of a-chymotrypsin and that the modified enzyme retained its intact active-site. These facts led to the postulate that, like the action of phenacyl bromides or benzyl bromides on a-chymotrypsin, the partial inactivation by (13-3) involves alkylation of Met-192 [179]. 

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