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I was tasked with figuring out the order of attaching the functional groups to a benzene ring for the synthesis of 1-(3-chloro-5-nitrophenyl)-2,2-dimethylpropan-1-one:

1-(3-chloro-5-nitrophenyl)-2,2-dimethylpropan-1-one

I propose the following order:

  1. the ketone from an acid chloride;
  2. the chlorine with $\ce{Cl2}$ and $\ce{FeCl3};$
  3. the nitro group with $\ce{HNO3}$ and $\ce{H2SO4}.$

My logic is that after adding the carbonyl group, the chlorine group should be added because adding the nitro group second would make the ring too deactivated for the chlorine later on. However, I am not sure about the relationship between the strength of the deactivator and its ability to meta-direct.

$\ce{Cl},$ being a ortho/para director, would want the nitro group to be added ortho or para to itself, but the carbonyl would prefer meta substitution. Because the carbonyl is a moderate meta director and halogens are weak ortho/para directors, does this mean that the carbonyl’s influence would “win out”?

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    $\begingroup$ Your approach is reasonable. Acetophenone forms 3,5-dinitro-acetophenone upon nitration. This product undergoes selective Zinin reduction to 3-amino-5-nitro-acetophenone. A Sandmeyer reaction here would be expected to substitute chlorine for the amino group. Your ketone would likely be amenable to this synthetic route. $\endgroup$
    – user55119
    Feb 25 at 16:59
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    $\begingroup$ A follow up. You plan to start with benzoyl chloride. What is your nucleophile, t-butyllithium? I would be concerned about over addition in spite of the bulkiness of the ketone that is formed. A safer route is benzaldehyde and t-butyllithium followed by oxidation of the secondary alcohol to the desired ketone. $\endgroup$
    – user55119
    Feb 25 at 18:29

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