This is something that was run across. Was posted in another thread, but seemed lost amongst the noise. Still seems pretty interesting.Tet Let 39 (1998) 5323-5326 Zhao et al
"A Novel Chromium Trioxide Oxidation of Primary Alcohols to the Carboxylic Acids"
...and secondary alcohols to ketones in, I quote, quantitative yields!
by adding a solution H5IO6 (periodic acid)XS/CrO3(cat amt) in wet MeCN (0.75% water) to the alcohols at 0-5 C ~ 1h
for example, in the paper, P2P-ol to P2P 98% yield with
0 C/ 1.25 eq periodic acid / 0.6 mol% Chromium trioxide
Granted, acetonitrile ain't that easy to find in the hardware store, nor is periodic acid. Frick.
SWIPP really fancies this oxidation, straight out of Vogel, and found with T.F.S.E.TM
The prob with MDP2Pol seems to be that it cannot be heated, hence must be extracted another way, used quickly and oxidised in mild conditions.
What about this: Make the Pol in cold acid/water conditions then extract with ether for this next reaction:
FROM VOGEL:
An excellent method for the conversion of ether-soluble secondary alcohols to the corresponding ketones is by chromic acid oxidation in a 2 phase ether-H2O system. Reaction is carried out at ~25degC with the stoichiometry of chromic acid calculated on basis of above equation:
3x(secondary alcohol) + Na2Cr2O7 + 4H2SO4 --->
3x(ketone) + Na2SO4 + Cr2(SO4)3 + 7H2O
The success is due to rapid formation of the chromate ester of the alcohol which is extracted into the aqueous phase, followed by ketone formation which is extracted back into ether phase and is thus PROTECTED FROM UNDERSIRABLE SIDE REACTIONS!!
Straight out of Vogel, his example being:
0.25mol of octan-2-ol in 100ml ether and add dropwise 125ml (O.083mol) of chromic acid over
15mins while ether soln vigourously stirred by mag stirrer.
Keep at room temp.
Stir another 2hrs at rm temp, transfer to separating funnel.
Extract ether layer, wash green Cr layer with further ether.
wash with 40ml sat. NaHCO3, then 40ml sat. NaCl, then dry with anhydrous NaSO4, filter, evap etc.
Yield: 81%
CHROMIC ACID PREP (500ml):
100g (0.33mol) Na2Cr2O7 dihydrate in 300ml H2O. Slowly add 134g (1.34 mol 98% sulfuric)
Cool, make volume up to 500ml with H2O.
There it is, it looks good, because as i was saying, you can make the MDP2Pol as usual in nice cold H2SO4/H2O conditions, extract with the right vol of ether and away you go. No distilling, no side reactions, no reflux.
Fucking beautiful, isn't it? :)
See Post 108780 (missing)
(dormouse: "Isolating MD-P2Pol from reaction matrix? -ReFlux", Novel Discourse) for further discussion, located conveniently in the annals of novel discourse for your viewing pleasure.
PrimoPyro
Vivent Longtemps la Ruche! STRIKE For President!
This is very possible the original publication of the method which later was quoted by Vogel, which later was quoted by ReFlux which later was quoted in Post 235579 (https://www.thevespiary.org/talk/index.php?topic=9036.msg23557900#msg23557900)
(PrimoPyro: "Re: A new oxidation for MDP2-ol?", Methods Discourse). You gotta love third-hand information ;)
Oxidation of secondary alcohols in diethyl ether with aqueous chromic acid.
Convenient procedure for the preparation of ketones in high epimeric purity.
Herbert Charles Brown, Chandra P. Garg, Kwang-Ting Liu
J. Org. Chem. 36, 387-390 (1971) (https://www.thevespiary.org/rhodium/Rhodium/pdf/chromate.2-phase.alc-ox.pdf)
(https://www.thevespiary.org/rhodium/Rhodium/pdf/chromate.2-phase.alc-ox.pdf)
Convenient procedures have been developed to convert secondary alcohols into ketones in excellent yield and high epimeric purity utilizing oxidation of the alcohol in diethyl ether with aqueous chromic acid. In one procedure the stoichiometric amount of sodium dichromate and sulfuric acid in water is added to the diethyl ether solution of alcohol at 25-30°C and the reaction is continued for 2 hr.
To our surprise, the oxidation of secondary alcohols proceeded very simply and cleanly in a two-phase system involving diethyl ether and a water solution of sodium dichromate and sulfuric acid. There appeared to be significant advantages to such an oxidation procedure. Consequently, we decided to undertake a detailed study.
In one early experiment we observed that, when a solution of cyclohexanol was contacted at 25°C with an aqueous solution of the calculated quantity of sodium dichromate and sulfuric acid, the cyclohexanol disappeared almost immediately from the ether phase. Evidently, the cyclohexanol must be rapidly esterified and the chromic acid ester is extracted into the aqueous phase. Ketone then begins to appear at a moderate rate and is extracted into the ether phase as it forms.
The ether phase then protects the ketone from undesirable side reactions, such as further oxidation or epimerization. Indeed, it proved possible to develop procedures which give nearly quantitative yields of ketones from a wide variety of secondary alcohols, with remarkably low epimerization for derivatives subject to this side reaction.
Chromic Acid Solution
The chromic acid solution used for the oxidation was prepared from the appropriate amount of sodium dichromate and sulfuric acid as indicated by the following equation.
3 R2CHOH + Na2Cr2O7 + 4 H2SO4 -> 3 R2C=O + Na2SO4 + Cr2(SO4)3 + 7 H2O
The chromic acid solution is prepared by dissolving 100 g (0.33 mol) of sodium dichromate dihydrate in 300 ml of water. The sulfuric acid (97%), 136 g (1.34 mol), was then added. The solution was then diluted to 500-ml total volume. This solution will oxidize 1.00 mol of secondary alcohol by procedure A.
Oxidation of l-(-)-Menthol in Diethyl Ether with Stoichiometric Amount of Chromic Acid
A Representative Procedure A
Diethyl ether, 20 ml, and 7.80 g (50 mmol) of l-(-)-menthol were placed in a 100-ml three-necked flask fitted with a stirrer, a condenser, and an addition funnel. Chromic acid solution (25 ml) was added to the stirred solution over 15 min, maintaining the temperature at 25-30°C. After 2 hr at room temperature, the upper ether layer was separated and the aqueous phase was extracted with two 10-ml portions with ether. The combined ether extracts were washed with saturated sodium bicarbonate and then water. GC indicated 97% l-(-)-menthone, a trace of isomenthone, and 1.5% menthol. Vacuum distillation through a short Vigreux column gave 6.45g (84%) of l-(-)-menthone, bp 86-67°C/4mmHg.
Evidently, the cyclohexanol must be rapidly esterified and the chromic acid ester is extracted into the aqueous phase. Ketone then begins to appear at a moderate rate and is extracted into the ether phase as it forms.
Do you guys understand what it means? ;) What it PROBABLY means is that our alkene, not alcohol, will just like that get esterified with chromic acid and oxidized directly to ketone in one-pot!
Now, this might need some different temp. comditions... Or a different conc. of H2CrO4 (does anyone have a clue about the rate of esterification of alkenes as compared to sec. alcohols?)
But anyway, it should bee very easy to test.
Another implication is that ether's only role is to provide a two-phase system and it can bee replaced with smth else - like EtOAc, possibly?
What do you think?
Antoncho