Addition of cyclohexanone to indole with MeONa and MeOH [closed]








**Closed.** This question is [off-topic](/help/closed-questions). It is not currently accepting answers.
 
 






---








 **Homework questions** must demonstrate some effort to understand the underlying concepts. For help asking a good homework question, see: [How do I ask homework questions on Chemistry Stack Exchange?](https://chemistry.meta.stackexchange.com/questions/141/how-do-i-ask-homework-questions-on-chemistry-stack-exchange)




Closed 5 months ago.








[Improve this question](/posts/173093/edit) 



I need to find this reaction mechanism and i have run out of ideas. I have tried using -OMe on both indole and on cyclohexanone in order to create an enolate but i cant think of anything else. Thank you in advance


[![enter image description here](https://i.stack.imgur.com/W6ppE.png)](https://i.stack.imgur.com/W6ppE.png)




The Comments have pretty much ruled out the existence of this reaction in the chemical literature. Like many exam questions the proposed reaction is conceptually possible but that doesn't mean that it occurs. The reaction for indole itself (**1b**), in principle, would be catalytic in base in that alkoxide is regenerated. Your indole (**1a**) requires stoichiometric base to neutralize the carboxylic acid in addition to the catalytic amount of base required to effect the reaction. In practice, an excess of base would normally be employed.  
  

Indole (**1b**) has a [pKa of ~21](https://www.scripps.edu/baran/heterocycles/Essentials1-2009.pdf) while methanol's [pKa is 15.5](https://pubs.acs.org/doi/abs/10.1021/ja01489a008). This means that the concentration of resonance stabilized anion **2** is quite low. However, it is a better nucleophile than indole itself. Any addition of the nitrogen of **2** to cyclohexanone (**3**) will be unproductive because the reverse reaction is its only option. Addition of the carbon site to **3** leads to protonation of the alkoxide and regeneration of the indole nucleus as shown in structure **4**. During the course of these steps either **4** or **5** may be protonated and deprotonated. Species **5** effects elimination of hydroxide affording **6**, which upon vinylogous deprotonation leads on to the final product **8** via **7**. *continued*


![](https://i.stack.imgur.com/xzj1Q.jpg)
The foregoing reaction is a case of a strong nucleophile (**2**) and a decent electrophile (**3**). What about the use of a strong electrophile (**9**) and a decent nucleophile (**1**)? An acid-catalyzed route is less problematic having the [Vilsmeier-Haack formylation of indole](https://www.organic-chemistry.org/namedreactions/vilsmeier-reaction.shtm) as a precedent. Accordingly, species **10**, which is formed from protonated cyclohexanone **9** and indole **1**, aromatizes to indole **11**. Acid-catalyzed loss of water from **12** affords **8** via **13**.  
  

If I were setting out to accomplish this reaction, I would certainly opt for the acid-catalyzed route.


![](https://i.stack.imgur.com/rX8iI.jpg)
 1