Acme
(Member)
03-29-00 03:30
No 107446
      A new oxidation for MDP2-ol?
(Rated as: good read)
    

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.
 

 
 
 
 
    terbium
(Old P2P Cook)
11-10-01 22:15
No 235260
      Re: A new oxidation for MDP2-ol?     

Probably not many people have commented on this because the most facile route to MDP2P-ol is oxymercuration/borohydride reduction of safrole. Wacker on safrole or peracid on isosafrole are both easier and more OTC.
 
 
 
 
    Dr_Sister
(Hive Bee)
11-10-01 22:29
No 235266
      Re: A new oxidation for MDP2-ol?     

if hell bent on that route a Jones reagent (CrO3 and H2SO4) might be simpler and more otc route. It has been discussed here, but don't recall anybeee posting results.

7.10.01
 
 
 
 
    terbium
(Old P2P Cook)
11-11-01 00:53
No 235298
      Re: A new oxidation for MDP2-ol?     

if hell bent on that route a Jones reagent (CrO3 and H2SO4) might be simpler and more otc route
Maybe this would work or maybe it would oxidize the alcohol all the way to the phenylacetic acid.
 
 
 
 
    Rhodium
(Chief Bee)
11-11-01 05:57
No 235406
      Re: A new oxidation for MDP2-ol?     

There is no problem whatsoever oxidizing MDP2Pol to MDP2P, the major problem is to form the MDP2Pol in the first place. We need a workable safrole hydration method, besides that we only have that nasty mercuration reaction, and of course the elegant 5-bromo-1,3-benzodioxole grignard + propylene oxide reaction. I wonder why not more people use that method of making P2Pol's of differing substitution patterns.
 
 
 
 
    PrimoPyro
(Hive Bee)
11-11-01 06:25
No 235417
      Re: A new oxidation for MDP2-ol?     

SWIPP has a racing fuel catalog, where he has dreamed of buying MeNO2 from in multigallon quantities, along with MeOH, and they also sell propylene oxide.....pure, as an additive. He didn't think it was useful, though.

Jesus, are these guys on OUR side!??tonguecool
 
 
 
 
    Vibrating_Lights
(Hive Bee)
11-11-01 21:13
No 235577
      Re: A new oxidation for MDP2-ol?     

90%MeNO2 is used as fuel in dragcars.  just go to a trashy looking place where they build drag cars.  there is at least one in every city. The other 10% is ethanol.  Show up around closing time with a six pack and a joint and youre in.  TEEHEE If you are good you might even get a gallon for free.  they can only get in in barrelswink

There are two things that foul the formation of the 2Pol  Heat and Acidic conditions.  Swim Suspects that if the regents are cold and the acid is neutralized right after the water addition before seperation. It might substantialy increce the life of the 2pol.  Then a non acidic oxidation procedure could be used to oxidese the alcohol to the ketone.  Ie.H2O2
 
 
 
 
    PrimoPyro
(Hive Bee)
11-11-01 21:26
No 235579
      Re: A new oxidation for MDP2-ol?     

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? smile

See Post 108780 (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!
 
 
 
 
    Acme
(Hive Bee)
11-12-01 03:59
No 235717
      Re: A new oxidation for MDP2-ol?     

I think t-Boc made MALPHA.  Which will get you fucked up

The post I made was mostly gee-whiz, 98% Wow, because Chromium VI is a heinous nasty to be avoided IMO, along with routes that involve Hg

and for the oxidation, PCC/celite would be my choice
 
 
 
 
    terbium
(Old P2P Cook)
11-12-01 05:11
No 235753
      Re: A new oxidation for MDP2-ol?     

Referring to:
--------------------------------------------------------------------------------

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:

Who said this? I assume that you and V_L are making reference to some sort of alkene hydration using sulfuric acid? I don't think that this will work. People who claim that MDP2P-ol is unstable, in fact, never had any MDP2P-ol. They are just using the supposed instability of MDP2P-ol as part of a fallacious argument to explain the failure of the sulfuric acid hydration procedure. MDP2P-ol obtained via oxymercuration/borohydride reduction of safrole is stable at room temperature and can be oxidized in high yield with pyridinium chlorochromate to MDP2P.
 
 
 
 
    terbium
(Old P2P Cook)
11-12-01 05:37
No 235769
      Re: A new oxidation for MDP2-ol?     

And what is so nasty about chromium VI?
You didn't see the movie Erin Brokovich? Chromium VI is a nasty US capitalist corporate conspiracy to poison the proletariat.

IMHO, chromium VI is not a problem to work with. It is easy to convert it to the nontoxic Cr III form for disposal. When I was a kid I used to buy ammonium dichromate by the pound to watch it burn.
 
 
 
 
    Acme
(Hive Bee)
11-13-01 04:24
No 236096
      Re: A new oxidation for MDP2-ol?     

What were your yields for making P2P?
 
 
 
 
    terbium
(Old P2P Cook)
11-13-01 07:10
No 236147
      Re: A new oxidation for MDP2-ol?     

What were your yields for making P2P?
To whom are you speaking?
 
 
 
 
    Acme
(Hive Bee)
11-13-01 07:21
No 236149
      Re: A new oxidation for MDP2-ol?     

You are the Old P2P cook

who else

I was just joking

insinuating that you would have Jones'ed with your Chromium (or this new method I am so hot on) back in the day before PPA got scarce

or are you now and always have been and will continue into the future to be a PCC fan?
 
 
 
 
    terbium
(Old P2P Cook)
11-13-01 07:45
No 236153
      Re: A new oxidation for MDP2-ol?     

before PPA got scarce
Not sure what PPA is. PhenylPropanolAmine?

When I could no longer buy Mallinckrodt P2P I made it from phenylacetic acid and acetic anhydride. When phenylacetic acid became hard to get I made that from phenylacetonitrile. By the time phenylacetonitrile and acetic anhydride became hard to get I had acquired considerable stashes of benzaldehyde and nitroethane but decided to get out of the business around that time. I never used Cr VI to make P2P though I once did use Cr VI in the form of pyridinium chlorochromate to make MDP2P.

or are you now and always have been and will continue into the future to be a PCC fan?
Pyridinium ChloroChromate?
Naw, pyridinium chlorochromate is a pain to work with. Doesn't really dissolve in methylene chloride and instead forms a sticky, gunky mess. Jones reagent would be much better if it works.

 
 
 
 
    sunlight
(Pioneer Researcher)
11-13-01 14:40
No 236245
      Re: A new oxidation for MDP2-ol?     

I made years ago a test with the cold sulfuric and Jones reagent and there was nothing interesting there. It was a single test, so I can't conclude that it doesn't work, but probably it doesn't work. I've never seen a reliable success with it in the Hive.
 
 
 
 
    otto
(Newbee)
11-14-01 00:26
No 236405
      Re: A new oxidation for MDP2-ol?     

hi terbium,

the fact that REAL MDP2Pol (from mercuration) is stable and the product formed in the "H2SO4-process" is not, is intriguing me a long while. there is a post about making methylsulfuric acid salts for MeNO2, so otto is asking himself wether the product formed from safrol and sulfuric acid after treatment with cold water is indeed the MDP2Pol. it seems that there is rather built the sulfuric acid mono ester of MDP2Pol:

MDP-CH2-CH(OSO3H)-CH3


by 1H-NMR-spectrum there would be practically no difference between MDP2Pol and this monoester. otto remembers the NMR-data of the "H2SO4-process" beeing posted somewhere in the hive.

otto
 
 
 
 
    Rhodium
(Chief Bee)
01-06-04 12:04
No 480724
      High-yield 2 alc. ox. Na2Cr2O7/Et2O/H2O/H2SO4
(Rated as: excellent)
    

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 (PrimoPyro: "Re: A new oxidation for MDP2-ol?", Methods Discourse). You gotta love third-hand information wink


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) (../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 25-30C 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 25C 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 25-30C. 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 86-67C/4mmHg.


The Hive - Clandestine Chemists Without Borders
 
 
 
 
    Antoncho
(Official Hive Translator)
01-06-04 15:39
No 480741
      Implications!     


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?wink 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

 
 
 
 
    Rhodium
(Chief Bee)
01-06-04 15:57
No 480744
      H2Cr2O7 + Hg(II) => Wacker Emulator     

They tried EtOAc, but with less favorable results (see the full article).

Chromic acid can be used with a Hg2+ catalyst as an alternative to the Wacker oxidation of alkenes to ketones, it doesn't work well on its own. Let me just find that article...

The Hive - Clandestine Chemists Without Borders