Home >
Community >
How to synthesize cyclopentane from cyclohexane?
Upvote
30
Downvote
+ Biochemistry
+ Synthesis
Posted by
Mike King
How to synthesize cyclopentane from cyclohexane?
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).
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).
Oops, forgot about that. Wolff-Kishner or Clemmensen should work.More
Upvote
VOTE
Downvote
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.
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.
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.
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.
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. JACS1960, 82, 4307.
4. J. Chem. Soc., Chem. Commun.1983, 939.
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. JACS1960, 82, 4307.4. J. Chem. Soc., Chem. Commun.1983, 939.
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).
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).
More
VOTE
VOTE
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.
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.
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.
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.
More
VOTE
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.
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.
More
VOTE
VOTE
Why not just use the Aldol condensation on the dialdehyde produced from ozonolysis and save some steps?
Why not just use the Aldol condensation on the dialdehyde produced from ozonolysis and save some steps?
More
VOTE
VOTE
VOTE