Our professor talked about the six stages of the synthesis of sulfa-drugs, which are:

  1. nitration of benzene
  2. reduction of nitrobenzene
  3. acylation of aniline
  4. reacting acetanilide with chlorosulfonic acid
  5. treating the product with a primary amine
  6. subsequent hydrolysis of acetyl groups

If we skip step 3, and let aniline react with chlorosulfonic acid, and then go till step 5, could sulfonamide be synthesized? Why do we perform acylation of aniline if we just have to remove the acyl group by subsequent hydrolysis later?

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    $\begingroup$ Because aniline does not sulfonate in the ring unless you protect the NH2 $\endgroup$ – Waylander May 9 '18 at 7:59

The main problem encountered during electrophilic substitution reactions of aromatic amines is that of their very high reactivity. Substitution tends to occur at ortho- and para-positions. If we have to prepare monosubstituted aniline derivative, how can the activating effect of –NH2 group be controlled ?
This can be done by protecting the -NH2 group by acetylation with acetic anhydride, then carrying out the desired substitution followed by hydrolysis of the substituted amide to the substituted amine

The lone pair of electrons on nitrogen of acetanilide interacts with oxygen atom due to resonance as shown below:


Hence, the lone pair of electrons on nitrogen is less available for donation to benzene ring by resonance. Therefore, activating effect of –NHCOCH3 group is less than that of amino group.

Moreover, in the strongly acidic medium, aniline is protonated to form the anilinium ion which is meta directing. meta direction

However, by protecting the –NH2 group by acetylation reaction with acetic anhydride, the reaction can be controlled and the p derivative can be obtained as the major product.

source: word to word from NCERT(INDIA) CLASS 12 chemistry ;) http://ncert.nic.in/NCERTS/l/lech204.pdf

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    $\begingroup$ Don't rely on NCERT. They are very misleading. $\endgroup$ – Nilay Ghosh May 9 '18 at 13:01
  • $\begingroup$ ncert is one of the best books i have seen $\endgroup$ – amish dua May 9 '18 at 13:42
  • $\begingroup$ your welcome but i am just a 17 year old kid so sir feels a little awkward :) $\endgroup$ – amish dua May 11 '18 at 15:35
  • $\begingroup$ I am saying this from my experience. I used to study from that book and all I can say, I regret it. $\endgroup$ – Nilay Ghosh Apr 17 '19 at 19:09

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