Sciencemadness Discussion Board

secondary alcohol --> ketone, without dichromate

garage chemist - 14-10-2006 at 08:28

Does anyone know a generally applicable method to convert secondary alcohols to the ketone that doesn't use dichromate?

My problem is to make cyclohexanone from cyclohexanol. I have a procedure for this (in Vogel) but it uses sodium dichromate. I think it is wasteful to use dichromate for this.

Is there a different oxidant which can be used? Ideal would be a method which uses H2O2 and a catalyst.

KMnO4 ruptures the ring and makes adipic acid, so this is not useable.

guy - 14-10-2006 at 11:22

Sodium hypochlorite?

solo - 14-10-2006 at 11:38

Have you seen this over at Reference Section in the "Articles of Interest"..........solo

Note : I have edited this post to incoude the article for the sake of continuity


Trichloroisocyanuric Acid/KBr as a Catalytic System for the Chemoselective Oxidation of Benzylic and Secondary Alcohols Chemoselective Oxidation of Benzylic and Secondary Alcohols
Mohammad Ali Zolfigol,*a Farhad Shirini,b Arash
Synthesis Issue 12, pg.2043,2006



Abstract
Chemoselective oxidation of benzylic and secondary alcohols were proceeded by using a catalytic amount of KBr in the presence of trichloroisocyanuric acid and wet SiO2 under mild and heterogeneous conditions with excellent yields.

Key words: trichloroisocyanuric acid, benzylic and secondary alcohols, chemoselective oxidation

[Edited on 15-10-2006 by solo]

Attachment: Trichloroisocyanuric Acid:KBr as a Catalytic System .pdf (70kB)
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jim20/20 - 14-10-2006 at 12:25

bleach
http://www.ehcweb.ehc.edu/faculty/ALEONG/cloroxmodule/reacti...

since you mentioned H2O2
http://www.wanfangdata.com.cn/qikan/periodical.Articles/kxtb...
needs translation

[Edited on 14-10-2006 by jim20/20]

not_important - 14-10-2006 at 22:39

Less common ways, if the above useful ideas don't grab you:

Passing the vapour over finely divided copper or copper chromite at ca 200 - 250 C.

Run a Meerwein-Ponndorf-Verley reduction using the cyclohexanol are the reducing agent and acetone as the oxidiser, distilling the isopropanol off in a flood of acetone.

MnO2 and somewhat diluted H2SO4 as oxidiser, steam distill the ketone out of the reaction mix as the alcohol is dropped in.

Pass the alcohol vapour over heated MnO2.

Sergei_Eisenstein - 15-10-2006 at 01:28

As a sidenote, the Swern oxidation is an academic alternative for those working with small amounts and disliking chromium-based oxidations.

garage chemist - 15-10-2006 at 03:47

OK, hypochlorite is the way to go- though, you can't make methylketones with it since those would be subject to the haloform reaction as soon as they are formed. But cyclohexanone won't do that.

A problem is that the bleach in german stores ("DanKlorix") has only 2,6% NaOCl. Therefore, one would have to use more than double as much as with Chlorox, with lower yields due to greater dilution and therefore less efficient extraction of product.

Several solutions to this problem:
- making chlorox myself, from chlorine gas and NaOH solution of correct concentration
- making "bromox" from bromine and NaOH: this has the advantage that bromine can be weighed exactly, allowing for a precisely known oxidiser content of the solution
- making NaOCl by dissolving TCCA in NaOH solution. I have done this before in order to make chloroform (there was a thread on this subject here).
However, the resulting NaOCl solution is strongly alkaline- and adding HCl as done in the reference above would result in reprecipitation of TCCA.

So method 1 or 2 should be tried.

TCCA/KBr- I haven't looked at that reference, I will do so as soon as I have the password for references.

[Edited on 15-10-2006 by garage chemist]

The haloform reaction is of no consequence

chemytron - 15-10-2006 at 08:10

Just use an excess of alcohol to use up all the oxidant if you're really that worried about the haloform reaction.

But a word of advice: Don't assume anything the article doesn't cover. If there is no mention of the haloform reaction in it, then why worry about it?

Anyway, acetone from IPA using this method is fast -- really fast -- and simple. And the reaction is easy to control.

The reactions in question use sodium hypochlorite and calcium hypochlorite as oxidants, respectively.

J.O.C. 1980, 45, 2030 & 1982, 47, 364

J.C.E. 1985, 62, 519

Tetrahedron Letters 1982, 23, 4647

Note: Sodium Bisulfate can be used in place of the acetic acid.

-Chemytron

[Edited on 15-10-2006 by chemytron]

jim20/20 - 15-10-2006 at 13:06

Quote:
Originally posted by garage chemist
A problem is that the bleach in german stores ("DanKlorix") has only 2,6% NaOCl. Therefore, one would have to use more than double as much as with Chlorox, with lower yields due to greater dilution and therefore less efficient extraction of product.
[Edited on 15-10-2006 by garage chemist]


just use pool chlorine
read Tet. Lett. 23(1), 35-38 (1982)

hinz - 15-10-2006 at 15:13

You can easy avoid the halogenation of cyclohexanone by keeping the pH neutral, so there won't be any acid, nor a alkaline catalysed halogenation. The raction with TCCA yields HCl a byproduct, so adding any proton catcher like Et3N seems to be necessary.
You're a garage chemist, so you won't have anything that nice, so you might try it with CaCO3 or NaHCO3, basically anything that isn't as basic that it might steal the 2/6 hydrogen and thus making a nucleophile from cyclohexanone, alias alkaline catalysed halogenation or haloform reaction.

I'm not sure, but it's not plausible to me why no acid catalysed reaction at the product occours in the oxidation with TCCA, without using moderate base to catch HCl or a large excess of cyclohexanol, like chemytron mentioned it.


[Edited on 16-10-2006 by hinz]

garage chemist - 15-10-2006 at 20:47

I want to avoid excess of cyclohexanol, as its separation from ketone is difficult (boiling points too close together, and bisulfite adduct is not so easy to work with).

Maybe it is possible to avoid hypochlorite. I recently catalytically dehydrogenated some 1,4-butanediol to the lactone with copper oxide (forms finely divided copper, which is the true catalyst). But that reaction needed 200°C to work, which would mean that with cyclohexanol one would have to work in the gas phase. Maybe using a stochiometric instead of catalytic quantity of copper oxide does the trick.

The TCCA/KBr system sure is very interesting, especially for the synthesis of benzaldehyde from benzyl alcohol.
I'm definately going to try making cyclohexanone with this.
But what is this "wet SiO2"? Ground up wet sand from the garden?




[Edited on 16-10-2006 by garage chemist]

not_important - 15-10-2006 at 21:52

Quote:
Originally posted by garage chemist
...
Maybe it is possible to avoid hypochlorite. I recently catalytically dehydrogenated some 1,4-butanediol to the lactone with copper oxide (forms finely divided copper, which is the true catalyst). But that reaction needed 200°C to work, which would mean that with cyclohexanol one would have to work in the gas phase. Maybe using a stochiometric instead of catalytic quantity of copper oxide does the trick.


You can use an excess of copper oxide, it helps drive the reaction to completion, provided the rest of alcohol structure is relativly resitant to oxidation. When it is difficult to separate alcohol from ketone you can condense both, and repeat the vapour phase pass over either copper oxide or the reduced copper catalyst until the alcohol is completely converted.
Quote:
But what is this "wet SiO2"? Ground up wet sand from the garden?


Silica gel or very fine SiO2 such as is used for chromatography, not sand. Large surface area, with absorbed water or even water in its pores.

S.C. Wack - 15-10-2006 at 22:00

As far as I could tell, none of the BKCS articles cited mentioned what wet SiO2 means exactly either, though they may also be of interest to you. Maybe some other article does.

No calcium hypochlorite is available OTC there?

1 mmol cyclohexanol/5 mmol (30%)H2O2/0.2 mmol FeBr3/no solvent ---24 hrs stirring @STP> 85% yield:
http://www.erowid.org/archive/rhodium/pdf/alcohol.oxidation....

Activated MnO2

chemytron - 16-10-2006 at 17:22

You could use a heterogeneous reaction using any non-polar solvent of your choice, cyclohexanol, stirred with activated manganese dioxide for a few hours, filtered and evaporated to get your desired cylcohexanone.

The activated manganese dioxide can be had by refluxing potassium permanganate with acetone until the purple/pink color dissipates and the solvent is clear. Filter, wash with distilled water, wash again with acetone, and let stand dry.

Simple but you have to bake in the oven the MnO2 to complete dehydration to make it active.

[Edited on 17-10-2006 by chemytron]

Sauron - 25-1-2007 at 02:27

Has anyone actually tried the TCCA oxidation of benzyl alcohol on a prep scale? Say 1 mol to 10 mols?

Because the lit. prep cited above is run on a 1 mmol scale.

A quick thought: the oxidation of 1 mol by direct scalup of their process will require 10 L DCM in a 22 L reactor and 20 L DCM for washing the filtrate afterwards. Altogether 30 L DCM and product to be dried and filtered again and rotavaped.

Good thing I have a 20 L rotavap and even then it will take 3 runs to recover c. 100 g benzaldehyde.

OK, the DCM can most likely be reused. Sand is cheap and the reagents are cheap and no heating is required for the rxn. And it is pretty fast (75 minutes on the 1 mmol scale.)

Anyone have any toughts on prospects of reducing the solvent volume to something a little more manageable?

I'd be very tempted to try, on say a 10 mmol scale, reducing the solvent volume by half, and if that still works, half again. Which would mean that on a 22L reactor basis, 4 mols could be processed per batch. Or 6-7 mols if one cares to go beyond the half-full rule of thumb, and work with a nearly full flask.

That way we could be recovering maybe 750 ml benzaldehyde per run. A wee bit more worthwhile.

Any comments?

(Later)

Hang on. Here's a much better procedure, also TCCA also room temperature, in acetone, and in presence of pyridine as an acid scavenger, although I expect that TEA or diethylaniline would work as well. (Pyridine is a chemosterilant. No kiddies for those exposed.)

As TCCA is cheap, this is better, not requiring large scale apparatus for a small amount of product.

[Edited on 25-1-2007 by Sauron]

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chemrox - 27-1-2007 at 22:09

Quote:
Originally posted by not_important
Passing the vapour over finely divided copper or copper chromite at ca 200 - 250 C.


Isn't this a bitch for heat control and cooling/collection apparatus? What is the setup?