Can a cyclic amine form an amide?

This is a question from the Cambridge International Examinations October/November 2017 [(pdf from papers.gceguide.com](https://papers.gceguide.com/A%20Levels/Chemistry%20(9701)/9701_w17_qp_42.pdf), [pdf via the Wayback Machine](https://web.archive.org/web/20190430124514/https://papers.gceguide.com/A%20Levels/Chemistry%20(9701)/9701_w17_qp_42.pdf)).


I need to understand why the secondary amine in the **serotonin** molecule does not undergo condensation reaction with $\ce{CH3COCl}$.  

Because, as far as I know, there should be an amide formation for this reaction.


Here's a picture of serotonin:


[![serotonin with highlighted NH group](https://i.stack.imgur.com/R7NmS.png)](https://i.stack.imgur.com/R7NmS.png)


I must be lacking some information making that $\ce{NH}$ unsuitable for this reaction. And I know that the other amine and the phenol reacts with $\ce{CH3COCl}$.




The heterocycle in this question is indole and is aromatic. This means that the N lone pair is delocalised and not readily available for nucleophilic attack. Think of it as similar in reactivity to a secondary amide nitrogen RCONHR. Generally you need to formally deprotonate to functionalise, though there are some interesting techniques using carbonyl azoles catalysed by DBU[1] and others using aldehyde and alcohol substrates.[2] Note that 3-unsubstituted indoles react with acyl halides by F-C acylation at the 3 position.[3] 


### References:


1. Heller, S. T.; Schultz, E. E.; Sarpong, R. Chemoselective N-Acylation of Indoles and Oxazolidinones with Carbonylazoles. *Angew. Chem. Int. Ed.* **2012,** *51* (33), 8304–8308 [DOI: 10.1002/anie.201203976](https://doi.org/10.1002/anie.201203976).
2. Maki, B. E.; Scheidt, K. A. Single-Flask Synthesis ofN-Acylated Indoles by Catalytic Dehydrogenative Coupling with Primary Alcohols. *Org. Lett.* **2009,** *11* (7), 1651–1654 [DOI: 10.1021/ol900306v](https://doi.org/10.1021/ol900306v). [PMID: 19320508](https://www.ncbi.nlm.nih.gov/pubmed/19320508) (with free text available).
3. Okauchi, T.; Itonaga, M.; Minami, T.; Owa, T.; Kitoh, K.; Yoshino, H. A General Method for Acylation of Indoles at the 3-Position with Acyl Chlorides in the Presence of Dialkylaluminum Chloride. *Org. Lett.* **2000,** *2* (10), 1485–1487 [DOI: 10.1021/ol005841p](https://doi.org/10.1021/ol005841p).


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If you consider the lone pair on that N-atom and apply Hückel's (4n+2)π-e rule to check aromaticity , it satisfies all the conditions. So in order to achieve aromatic-stabilisation the nitrogen's valency is no more available for condensation!


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