[pradeepk]

Hello,

I attached the problem.  I got a different answer than my professor, so I am just wondering if my method is correct.  I am just not sure about the first step in the retrosynthetic approach  Any help would be appreciated..thanks!

[spirochete]

One immediate problem I see is that Friedel Craft's reactions don't work on deactivated aromatic rings.  So while your method looks like it might work in principle because the ketone is meta directing, in reality the deactivated substrate would not give any product.  You might get some partial credit for it though.

Also I'm not sure if H2/Pd on carbon works for reducing carbonyl groups to alcohols.  It might, I just can't remember off the top of my head.  Typically one would use a hydride reducing agent to reduce ketones, not H2.

[pradeepk]

Ok so now matter what, if a compound deactivates the benzene ring, there can be no additions to it?  Because I thought that there were certain levels of deactivation.  For example, NO2 deactivates the benzene ring more than the ketone group, so the ketone group still allows some reactions.

[spirochete]

Not quite, the Friedel Craft's reaction is just an example of an electrophilic aromatic substitution (EAS) reaction that usually doesn't work on deactivated aromatic rings.  Most of the other EAS reactions you learn do work on deactivated rings, although more forcing conditions would be required.  Depending on your professor you may not have been taught this detail.  This isn't something you could deduce from first principles, it's just a practical detail you would have to be taught or learn in the lab through a failed experiment.

You are right, there are degrees of deactivation, with the nitro group being more deactivating than a ketone, because the nitro group is more electron withdrawing.

[BQ]

Not quite, the Friedel Craft's reaction is just an example of an electrophilic aromatic substitution (EAS) reaction that usually doesn't work on deactivated aromatic rings.  Most of the other EAS reactions you learn do work on deactivated rings, although more forcing conditions would be required.  Depending on your professor you may not have been taught this detail.  This isn't something you could deduce from first principles, it's just a practical detail you would have to be taught or learn in the lab through a failed experiment.

You are right, there are degrees of deactivation, with the nitro group being more deactivating than a ketone, because the nitro group is more electron withdrawing.

I've done friedel craft's in lab, it did give around 20% di-substituted product. It did happen, but in a low yield.

I will say this plan may work, but not the best.

[fledarmus]

I've done friedel craft's in lab, it did give around 20% di-substituted product. It did happen, but in a low yield.

I will say this plan may work, but not the best.

You've done what sort of Friedel Crafts? A Friedel Craft alkylation will frequently give di-substituted product, because an alkyl group is activating - the product is more active than the starting material. A Friedel Craft acylation of an activated benzene ring, like phenoxy or anilino, may also give multiple substitution, because the ring is still activated even with one mildly deactivating group attached. But a benzene with nothing but deactivating substituents? I'm with Spirochete, I've never seen that work.

[Cryolite]

Benzene --- H2SO4/HNO3, heat ---> 1,3-dinitrobenzene --- Sn/HCl ---> 1,3-diaminobenzene --- NaNO2/HCl, 0°C; CuBr ---> 1,3-dibromobenzene --- Mg/THF(anh.); 2eq. acetaldehyde; H3O+ ---> desired product

The difficult part is making the 1,3-dibromobenzene, but then is one step since the side chains are symmetric.

[Arctic-Nation]

Not sure if this will actually work, but benzene -> nitrobenzene -> aniline -> acetanilide -> 2,4-dibromoacetanilide -> 2,4-dibromoaniline -> 1,3-dibromobenzene.

[OC pro]

@Cryolite: Diazotation of diamines is tricky and often gives triazoles. This route will not work.

The suggestion from Arctic-Nation sounds good.