Bromobenzene Friedel-Crafts acylation

Partial rate factors may be used to estimate product distributions in disubstituted benzene derivatives. The reactivity of a particular position in o-bromotoluene, for example, is given by the product of the partial rate factors for the corresponding position in toluene and bromobenzene. On the basis of the partial rate factor data given here for Friedel-Crafts acylation, predict the major product of the reaction of o-bromotoluene with acetyl chloride and aluminum chloride. 

More recently (Scheme 3) it has been recognised that a very wide range of different, all useful, intermediates can be efficiently prepared from the 1-alkyl- or 1-alkoxy-4-bromoben2enes (16 and 18), easily derived from bromobenzene (14) and 4-bromophenol (17), respectively. The alkyl material (16) is prepared from bromobenzene (14) by a Friedel-Crafts acylation and a subsequent reduction (the same procedure as described in Scheme 1), whereas the alkoxy analogue (18) is more easily prepared by the (9-alkylation of 4-bromophenol (17). 

Bromine is an ortho, para director, acetyl a meta director. Reasoning backward from the target, disconnection a makes electrophilic bromination of acetophenone the last synthetic step disconnection b makes Friedel-Crafts acylation of bromobenzene the last step. Of the two approaches, only bromination of acetophenone delivers the desired meta relationship of the two substituents and suggests the following synthesis. 

Preparation by Friedel-Crafts acylation of bromobenzene with m-nitrobenzoyl chloride, reduction of the obtained 4-bromo-3 -nitrobenzophenone and diazotization of the resulting 3-amino-4 -bromobenzophenone, followed by hydrolysis of the diazonium salt [900]. 

The synthesis of two four-terminus systems with two methylene conduction barriers is shown in Scheme 3.31. The dibromoxylene was oxidized and converted to the difacid chloride) 54. Friedel-Crafts acylation of 54 with bromobenzene was sluggish and low yielding. However, the tetrabromobis(arylketone) 56 was conveniently prepared by treatment of 54 with l-bromo-4-trimethylsilylbenzene. The reduction of the... 

The best results were obtained when the less activated substrate was used in the initial acylation and the more activated arene was used as the subsequent acceptor. With less activated substrates, such as diloro- and bromobenzenes, the chlorocarbonylation required a longer time and higher temperatures. Yields of 54-77% were obtained (Table 4.43) using 1.0 equiv. of each arene, rather than the several fold excess of one or the other often previously employed [950], Moreover, the conditions of the second Friedel-Crafts reaction are sufficiently mild that even an 0-... 

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