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I need to consider the retrosynthetic analysis and synthesis of dicyclohexylamine.

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For the retrosynthetic analysis, I have relied on the method of disconnections, which consists in splitting the target molecule into several fragments with one or more functional groups.

So, first of all, I have decided to disconnect (i.e., virtually break a bond) the C-N of the amine.

enter image description here

The reagent equivalents of these synthons I thought could be: aniline and cyclohexylmagnesium bromide. In such a case, the synthesis could be given by:

enter image description here

Aniline could be prepared by nitration of cyclohexane by reaction with nitric acid and sulfuric acid.

And, the organomagnesium reagent, from chlorocyclohexane with Mg in anhydrous ether.

Would this retrosynthetic analysis and synthesis method be appropriate?

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    $\begingroup$ Did you learn that in retrosynthesis, you usually make polar disconnections, in that one side is a nucleophile and the other side is an electrophile? You have chosen two nucleophilic starting materials, which will not work at all. Radical disconnections (like the one you have drawn, where each fragment has an unpaired electron) are possible, but more advanced, and certainly not needed in this case. $\endgroup$ Sep 9 at 8:39
  • $\begingroup$ Aniline is not cyclohexylamine. Aniline is an aromatic derivative of benzene not cyclohexane. And you certainly can't make either by nitrating cyclohexane. $\endgroup$
    – matt_black
    Sep 9 at 9:05

2 Answers 2

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Grignards reacting with primary amines act as bases giving the amine anion.

This can be done in one step by reductive amination of cyclohexanone with cyclohexyl amine. Further information here

Both of these starting materials are widely available so you do not need to consider their preparation.

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React formamide with 1-chlorocyclohexane. To make the chlorocyclohexane, you can hydrogenate chlorobenzene. To make formamide, you can add ammonia to ethyl formate or heat ammonium formate to dehydration. Then, just heat with NaOH to deprotect the amide protecting group and you have your compound. In my experience, its best to make N-C bonds using Halogens. I believe chlorocyclohexane would be the solvent itself or you can add something like water and a bit of K2CO3 to drive the reaction forward. And heat at reflux maybe if its going too slow. Monitor pH to see if the pH decreases, that means reaction is completing. Use pH meter in a rubber cork, samples with pH paper or just put in some universal indicator solution

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    $\begingroup$ Do you have a reference for the hydrogenation of chlorobenzene to chlorocyclohexane? I can only find references to hydrogenation giving loss of chlorine. $\endgroup$
    – Waylander
    Sep 10 at 17:49
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    $\begingroup$ I'm with @Waylander! $\endgroup$
    – user55119
    Sep 10 at 19:25

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