Bromo group, directing effect

The position of substitution in disubstituted thiophenes can, in most cases, easily be deduced from the directing effect of each substituent. Thus with a - -M-substituent in the 2-position and a —M-substituent in the 5-position, both substituents direct the entering group to the 3-position as is exemplified by the nitration of methyl 2-bromo-5-thiophenecarboxylate to methyl 2-bromo-3-nitro-5-thio-phenecarboxylate (109) or in the chlororaethylation of methyl 2-methyl-5-thiophenecarboxylate to methyl 2-methyl-3-chloromethyl-5-thiophenecarboxylate (110). °... 

If t he directing effects of the two groups oppose each other, the more powerful activating group has the dominant influence, but mixtures of products often result. For example, bromination of p-methylphenol yields primarily 2-bromo-4-methylphenol because —OH is a more powerful activator than -CH3. 

If a rapid stream of HC1 or HBr is led into an ice-cooled solution of 4-oxo-4-phenylbutenoic acid for 20 min and reaction is allowed to proceed for a further 3 h, 81% of 2-chloro-4-oxo-4-phenylbutyric acid or 90% of the 2-bromo acid are obtained,212 in this case the / -directing effect of the keto group overcomes that of the COOH group. 

Bromoacetanilide is slightly less reactive toward further electrophilic substitution than acetanilide, but it is still sufficiently reactive to be chlorinated under mild conditions without a strong Lewis acid catalyst. Thus, molecular chlorine dissolved in acetic acid chlorinates 4-bromoacetanilide to produce 4-bromo-2-chloroacetanilide (20) as shown in Equation 21.12. The formation of the 2- rather than the 3-chloro isomer demonstrates the more powerful directing effect of the acetamido group as compared to the bromo substituent. 

The bromo group can be installed in the correct location based on the directing effects of the propyl group. 

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