Substituent groups ortho-para directing

Whereas in benzene chemistry halogen substituents are ortho-para directing because of their weak donor effects, in thiophene the +M effect is strongest across the 2,3-bond. This means that a 2-chloro group gives... 

Electrophilic aromatic substitution in biphenyl is best understood by considering one ring as the functional group and the other as a substituent. An aryl substituent is ortho, para-directing. Nitration of biphenyl gives a mixture of o-nitrobiphenyl and p-nitrobiphenyl. 

The synthesis of URB597 was extremely challenging, more so for the positions of its substituents than for their structure. Both groups are located in meta positions relative to the bond between the rings. Problem 39 revealed that phenyl rings as substituents are ortho, para directing. Therefore electrophilic aromatic substitution reactions performed on biphenyl cannot serve as an entry to the preparation of this important compound. 

To make this compound from benzene requires two separate steps—bromination and nitration. Bromination followed by nitration will not produce the desired product, because a bromine substituent is ortho-para directing. In order to achieve the meta relationship between the two groups, nitration must be performed first. The nitro group is a meta director, which then directs the incoming bromine to the desired location. 

How is this useful Consider the preparation of l-chloro-3-ethylbenzene from benzene. Retrosynthetic analysis (Section 8-9) indicates that neither chlorobenzene nor ethylbenzene is suitable as the immediate precursor to product, because each substituent is ortho, para directing. However, we recognize that ethyl can be produced from acetyl, a meta director. Hence, acetylbenzene, readily prepared by Friedel-Crafts acylation, is a perfect relay point, because it can be chlorinated meta. After the carbonyl group has completed its directing job, it is reduced to the desired alkyl group. 

All alkyl groups not just methyl are activating substituents and ortho para direc tors This IS because any alkyl group be it methyl ethyl isopropyl tert butyl or any other stabilizes a carbocation site to which it is directly attached When R = alkyl... 

Our analysis of substituent effects has so far centered on two groups methyl and triflu oromethyl We have seen that a methyl substituent is activating and ortho para directing A trifluoromethyl group is strongly deactivating and meta directing What about other substituents ... 

Alkyl groups are as we saw when we discussed the nitration of toluene in Sec tion 12 10 activating and ortho para directing substituents Aryl and alkenyl substituents resemble alkyl groups in this respect they too are activating and ortho para directing... 

Often the directing effects of substituents reinforce each other Brommation of p mtrotoluene for example takes place at the position that is ortho to the ortho para directing methyl group and meta to the meta directing nitro group... 

Sometimes the orientation of two substituents m an aromatic compound precludes Its straightforward synthesis m Chloroethylbenzene for example has two ortho para directing groups m a meta relationship and so can t be prepared either from chloroben zene or ethylbenzene In cases such as this we couple electrophilic aromatic substitution with functional group manipulation to produce the desired compound... 

The greater stability of the intennediates arising from attack at the ortho and para positions compared with those formed by attack at the position rneta to the oxygen substituent explains the ortho, para-directing property of hydroxyl, alkoxy, and acyloxy groups. 

Any substituent whose atom attached to the benzene contains a lone pair of electrons is ortho-para directing (but not necessarily a ring activator). Substituents without a lone pair on the atom attached to the ring are likely meta directors (with the exception of alkyl groups and aromatic rings, which turn out to be ortho-para directors). 

Orientation Similarly, groups already present on the benzene ring direct the orientation of the new substituent to ortho, para or meta positions. For example, nitration of chlorobenzene yields ort/io-nitrochlorobenzene (30%) and para-nitrochlorobenzene (70%). 

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