Acyl bromides 2-chlorination

Aldehydes can be directly converted to acyl chlorides by treatment with chlorine however, the reaction operates only when the aldehyde does not contain an a hydrogen and even then it is not very useful. When there is an a hydrogen, a halogenation (12-4) occurs instead. Other sources of chlorine have also been used, among them S02Cl2 and r-BuOCl. The mechanisms are probably of the free-radical type. V-Bromosuccinimide, with AIBN (p. 912) as a catalyst, has been used to convert aldehydes to acyl bromides. 

As the introduction of a halogen into an acyl halide takes place more rapidly than into the acid itself, the substitution-products of the fatty acids are more conveniently prepared by the action of chlorine or bromine on these compounds. It is not necessary to isolate the latter the acid to be bromin-ated, for example, is mixed with red phosphorus, heated at about 80°, and bromine is slowly added. The phosphorus bromide first formed interacts with the acid to form the acyl bromide, which is converted by the free bromine present into a bromoacyl bromide. The latter yields with water the halogen substitution-product of the acid —... 

The reactions of 0-naphthol and 4-methoxyphenol with acetyl, propionyl, butyryl, 0-chloropropionyl and chloracetyl chlorides in acetonitrile produce some striking kinetic results109. The behaviour of acetyl, propionyl and n-butyryl chlorides fit reasonably well into the pattern for acetyl chloride in nitromethane and acetyl bromide in acetonitrile. However, with chloracetyl chloride the mechanism is essentially a synchronous displacement of covalently bound chlorine by the phenol and this process is powerfully catalysed by added salt with bond breaking being kinetically dominant. When no added salt is present the rate of hydrolysis of chloracetyl chloride is ca. 8000 times slower than that of acetyl chloride. Although, normally, in second-order acylation reactions, substituents with the greatest electron demand have been found to have the fastest rates, the reverse is true in this system. Satchell proposes that a route such as... 

Indanones are very useful and versatile intermediates in the synthesis of metallocene catalysts. Scheme 1 has the synthetic scheme originally used for the preparation of 2-alkyl-4-aryl-substituted ansa metallocenes [9-11]. In the first part of this sequence, the biaryl unit is assembled and the missing carbon atoms are introduced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic acid ethyl ester under basic conditions, followed by a decarboxylation, affords the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few standard transformations are required to complete the synthesis, finally yielding the desired metallocene. 

For example, when benzene is heated with methyl chloride or bromide in the presence of the catalyst anhydrous aluminum chloride, toluene, CHj.C Hj (i.e. methyl benzene) is obtained. The catalyst acts as an electron acceptor for a lone pair on the chlorine atom. This polarises the haloalkane or acyl group. 

The cleavage of the chiral auxiliary requires an oxidative decomplexation with bromine, chlorine, iodine, or cerium(IV) salts and others in the presence of water, alcohols, and amines yielding carboxylic acids, esters, and amides, respectively. In all cases, the stereochemical integrity of the newly created stereocenter is maintained, whereas the iron-based chirality is "sacrificed upon the decomplexation. For example, the decomplexation with bromine leads to a substitution of the acyl group by bromide under retention at the iron atom. However, the complex [(PPh3)(CO)(Cp)FeBr] is susceptible to racemization in solution [61]. 

Ketoenamine (115), which had previously been used in studies by Lao, Witter and Cheng (c/. Scheme 8) was condensed with ethyl acetoacetate to produce acylpyridone (116) (Scheme 17). Reduction of the acyl group to the alcohol and further treatment with POCk simultaneously dehydrated this alcohol to the vinyl group and converted the pyridone to the chloropyridine (117). Cuprous cyanide served to replace the chlorine with a cyano group giving (118) which was transformed to the methyl ketone (119) with methylmagnesium bromide. 

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