Meto-directing groups

In designing the synthesis of disubstituted benzenes, you must consider carefully the order in which the substituents are to be placed on the ring. For example, if you want to synthesize meto-bromobenzenesulfonic acid, the sulfonic acid group has to be placed on the ring first because that group will direct the bromo substituent to the desired meta position. 

As para-xylene is the most valuable xylene for use as a polymer intermediate, it is useful that ortho- and meto-xylene can be isomerized using zeolite catalysts. Two routes are possible disproportionation, that is swapping methyl groups between xylene molecules and direct isomerization, involving sequential shifts of methyl groups around the benzene ring. 

Direct resonance interaction with the substituent group cannot occur in the cr-complex for meto-substitution. As a result, the transition state leading to this [Pg.392]

The influence of two meto-interrelated DMGs can be concerted to direct the metalation in between them. LTMP metalates meta-znmc acid 9 in THF at 0°C at the doubly activated position (C2) [62]. The regiochemistry of this lithiation is truly thermodynamically controlled resonance and inductive effects favor removal of the H2 proton. LICKOR deprotonates preferentially the C4 position. To prepare 6-substituted benzoates, one has to (i) protect the C2 site by introducing a trimeth-ylsilyl group with LTMP, (ii) lithiate with s-BuLi/TMEDA, (iii) quench with an electrophile, and (iv) remove the protecting group in C2. 

Pyridine and oxime-directed acetoxylation has been reported by Sanford (Scheme 3.14). Treatment of the arenes below with Pd(OAc)2 and bis-acetoxyiodobenzene (BAIB) afforded the desired acetoxylated arenes in good yields with high levels of regioselectivity, greater than 20 1 in most cases, for the more steri-cally accessible ortfto-position. The transformation displayed wide functional group tolerance with respect to the meto-substituent on the arene. The utilization of oxone as the terminal oxidant displayed comparable reactivity to BAIB and provides a safe, greener alternative. Tandem acetoxylation processes have also been described. ... 

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