I propose the following synthesis.

  1. Oxidation of aldehyde to a carboxylic acid. This sets me up for FC acylation once I ...

  2. Attack the -OH with thionyl chloride ad form the acid chloride.

  3. Reaction with vanilla benzene in the presence of Lewis acid catalyst. Benzene won't go after acid chlorides unless there is some catalyst in the system.

  4. Now that the acid chloride is installed, I can go through the motions of getting rid of the pesky C=O group.

  5. Given that alkyl groups are slightly activating and are ortho/para directing, I can sulfonate with fuming sulfuric acid and expect a mixture of products (including the one desired by the synthesis). Sterics might favor the para product over the ortho product given the sheer size of the SO3 group.

General comments:

I did NOT sulfonate first, as that is an electron-withdrawing group akin to the nitro group. It deactivates the ring and is also a meta-director. I want a para-substituted product. Not a meta-substituted product.

Therefore, how reasonable is my synthesis? Is it correct?

Also would sulfonation before getting rid of the C=O work? Something tells me no; the C=O is able to withdraw electrons from the ring via resonance, and that would make it a meta-director.

enter image description here

  • 2
    $\begingroup$ Looks good, sulfonation as the last step is the way to go for the reasons you provided. $\endgroup$
    – ron
    Sep 29 '14 at 3:41
  • $\begingroup$ @ron thanks! Can't wait to ace this test b/c of you! $\endgroup$
    – Dissenter
    Sep 29 '14 at 3:45
  • $\begingroup$ Dissenter good luck! $\endgroup$
    – ron
    Sep 29 '14 at 3:46

Your synthesis looks reasonable, and it is correct to perform sulfonation as the very last step, because the alkanoyl group would be meta-directing for the reason you have provided.

You can simplify your synthesis by reducing the carbonyl group away in one step with the Clemmensen reduction, which works well for aryl-alkyl ketones produced by Friedel-Crafts acylation.

enter image description here

Alternatively, the Wolff-Kishner or Mozingo reaction could be used. Reducing the number of steps in your synthesis would in practice have the benefit of increased overall yield for the final product, as the yield of each single step is usually < 100 %.

  • $\begingroup$ When would yield for each step be = 100% then? $\endgroup$
    – Dissenter
    Oct 31 '14 at 21:18
  • $\begingroup$ @Dissenter When in each step, all educts are converted into the desired product, but this is hard to achieve in practice. The mechanisms of most organic reactions contain a lot of equilibria, and there are also often possible side reactions which lead to by-products. $\endgroup$ Oct 31 '14 at 21:24

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.