Does this route work to synthesize cyclopentane from cyclohexane?

  1. Free-radical halogenation.

  2. Elimination with strong base to form cyclohexene.

  3. Ozonolysis to make di-aldehyde.

  4. Oxidation to make di-carboxylic acid.

  5. Esterification with ethanol, acid, and heat.

  6. Alpha-proton elimination with ethoxide ion.

  7. Intramolecular attack of other carbonyl carbon; loss of ethoxide leaving group.

  8. Acid, high heat, water to return to carboxylic acid. Expulsion of ethanol.

  9. Heat for decarboxylication. Loss of carbon dioxide.

  10. Not illustrated: removal of carbonyl using Wolff-Kishner and Clemmensen.

I think a few modifications I could make are:

  1. Formation of methyl ester using diazomethane. This would not involve heat and acid. But it would involve something that is potentially explosive.

  2. Alternately, make an acid chloride and then go down to the ester if I wanted to avoid the heat involved with Fischer esterification.

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  • $\begingroup$ Whether this route works or not isn't the point. There is absolutely no good reason to make one readily available hydrocarbon from another via complex chemistry. $\endgroup$ – matt_black Feb 11 '20 at 15:38

Why not just use the Aldol condensation on the dialdehyde produced from ozonolysis and save some steps?

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  • $\begingroup$ What does the heat, copper, and quinolone do? $\endgroup$ – Dissenter Dec 2 '14 at 23:34
  • 2
    $\begingroup$ Just typical conditions for a decarboxylation, quinoline is a high boiling solvent. $\endgroup$ – ron Dec 2 '14 at 23:35

Your route looks good until the last step. After decarboxylation, the intermediate will be cyclopentanone. So all that will be left to do is reduce the ketone to an alkane (you probably know a couple of options).

  • $\begingroup$ Oops, forgot about that. Wolff-Kishner or Clemmensen should work. $\endgroup$ – Dissenter Dec 2 '14 at 22:32

I know this is an old thread that only just became back to life so it's probably no longer worth it, but I'd think you could shorten these routes a bit by using some ring-contraction chemistry (e.g. Favorskii):


Refs: 1. M. T. Musser, Cyclohexanol and cyclohexanone. Ullmann's Encycloedia of industrial chemistry, 2000. 2. Synth. Comm. 2007, 37, 4149. 3. JACS 1960, 82, 4307. 4. J. Chem. Soc., Chem. Commun. 1983, 939.

  • $\begingroup$ Thank you for your comment $\endgroup$ – Dissenter Feb 17 '20 at 9:28

I would go with a different route, I would aim to convert the cyclohexane into cyclohexanone maybe via cyclohexanol. I would be looking for some bacteria which can do a selective oxidation or I would aim for using some CH activation chemistry which Derek Barton worked on.

An alternative is to brominate cyclohexane to cyclohexyl bromide and then react with 2-nitropropane to form cyclohexanone under basic conditons. Here is a diagram showing the core of my route.

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I would want to react the cyclohexanone with nitric acid using vanadium as a cataylst to form adipic acid. I would convert this into the diethyl ester. I would then want to condense it with itself using a base such as sodium ethoxide to form a ketoester.

I would then react this with aqueous base and then aqueous acid to get cyclopentanone. I would then reduce this using either zinc amalgum in hydrochloric acid or hydrazine under basic conditions.

Another method which is a tad on the brutal side is to make the adipic acid and then to heat it up with a mixture of manganese carbonate and barium hydroxide to form the cyclopentanone. See Slomp,G. et al. - Journal of Organic Chemistry, 1960, vol. 25, p. 514 - 518 for the use of this type of reaction. This relates to the synthesis of phenylacetone from phenyl acetic acid and acetic acid using thorium dioxide. I have worked once with phenyl acetic acid and it has a disgusting smell, I recall it was like old socks.


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