P2P via 1-Phenyl-2-propanol?

[Moriarty]

I'm sure others have kicked this around, but the only real references I've found using the fuckin' search engine are halide (Br) substitutions.  Some involving hard to get oxygen sources and such, but none that look quit so simple as this.  Anyone ever thought about making P2P out of 1-phenyl-2-propanol using the Fenton Reaction, an oldie but a goodie.

                                       Fe++
C6H5CH2CHOHCH3 + H2O2--------------->C6H5CH2COCH3

P2P isn't really my forte, but interesting none the less.  I'm not positive how available 1-phenyl-2-propanol is, but I've found a couple of places that sell it and it appears to be unrestricted.  Any thoughts?
Who wants to play cops and dope fiends?

[ChemicalSolution]

SWIm is gonna go with a 'negative' on being able to get 1-phenyl-2-propanol...

But, in the event that your SWIM does, there is a dichromate/H2SO4 oxidation in DMSO that is so easy you could probably train a monkey to do it. It's good for oxidizing primary alcohols to aldehydes and secondary alcohols to ketones.

xoxo
Julia

[Moriarty]

Here's the problem with that.  First SWIM's not really in the market for any P2P as he's more interested in MDP2P, but the thought of buying methylenedioxyphenyl-2-propanol is rediculous and so specific that it just could never happen.  In prior threads I hear people refer to being able to puchase it, so I read some synths and realized that second problem I mentioned.  Second, most currently accepted methods rely on oxygen sources that are seriously suspect.  I don't know if it's listed 1 or just a watched chemical, but sodium dichromate, for instance, is very difficult to obtain (don't hold me to that).  So I came up with this idea, having seen this method in a chem book sometime in the past.  Not to mention DMSO is another one of those watched chems.  I don't know.  Part of what we do, as a matter of principal, is discover new methods.  This is how production continues, is it not?
Who wants to play cops and dope fiends?

[Aurelius]

Can you use that reaction to oxidize a terminal alcohol to the aldehyde without overoxidation?

[Antoncho]

Dear Julia, Moriarty, could you please post these procedures!

Thanx in advance,

Antoncho

[ChemicalSolution]

10g dichromate is disolved in 100g DMSO.  Benzyl alcohol (5.4g) is added.  Concentrated H2SO4 is added dropwise while keeping the temerature below 70C.   The reaction mixture is heated at 70C for an additional 30 min(somewheres in here the reaction mixture turnes dark green).

The reaction mixture is poured on ice and extracted with 3x100 portions of (DCM).  The organic layer is washed once with bi-carb (take advice from Julia-- do this in a beaker.. Otherwise you may blow the stopper off your sep funnel).  And again with water.

The paper uses et2O to extract this..  SWIM has done this extraction with both DCM and toluene.  Both have advantages and disadvantages--- DCM sometimes forms emulsions that take a while to seperate..  DCM can also carry DMSO with it--  this is usually not a problem with toluene..

Yields-- 85%


xoxo Julia

[slappy]

1-Phenyl-2-Propanol can be oxidized under swern conditions, DMSO and Trifluoroacetic Anhydride (or Oxalyl Chloride) in CH₂Cl₂, then Et₃N.

A better way, is to use a stiochiometric amount of CrO₃ with Periodic Acid (HIO4) in CH₂Cl₂. There is a paper in Tetrahedron Letters by the Merck process division about this, where they got P2P in 98% yields.  Only problem of course being the amount of Cr^VI used becomes a potential health hazard.

[Rhodium]

Slappy - that reference would be very appreciated.

[slappy]

The reference is Tetrahedron Letters 39 (1998) 5323-5326

I had it wrong though, it is a catalytic amount of CrO₃ with stoichiometric Periodic Acid (H₅IO₆) in wet MeCN. I think that a CrO₃/H₂SO₄ would work almost as well here, because you really wouldn't need the strong oxidising power of H₅IO₆, which is used in the paper to oxidise 1° Alcohols to Acids.

[foxy2]

Procedure for 1-phenyl-2-propanol
A stock solution of H5IO6/CrO3 was prepared by dissolveing H5IO6 (11.4 g, 50 mmol) and CrO3 (11.5mg, 0.6 mol%) in wet MeCN (0.75 v % water) to a volume of 114 mL (complete dissolution typically requires 1-2 hours).  Stock soln. 5.7 mL was then added to a solution of the alcohol (2.0 mmol) in wet MeCN (10mL, 0.75 v % water) in 30-60 minutes while maintaining reation temperature at 0-5C.  Mixture is aged at 0C for 0.5 hours and completion of reaction is confirmed by HPLC. The reaction is quenched by adding Na2HPO4 (0.60g in 10 mL H20).  Yeild 98% P2P.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Moriarty]

Aurelius:  Sorry for the delay in response, but I've been without a computer for a couple of days.  Very legitimate question.  "Carbohydrates undergo extensive decomposition when treated with Fenton's reagent."  Tetrahedron, 1963, Vol. 19, pp 1705.  That part is true.

However, the article referenced above describes a modified interpretation of the Fenton Reaction by Weiss-Haber using Fe+++ instead of Fe++ salts to slow the reaction and, thus, decomposition.  So that's an option if decomposition were to become a problem.  I don't believe it would.

Did I fail to understand your comment, or is that what you meant?  Also, by terminal alcohol did you mean tertiary?  Isn't 1-phenyl-2-propanol a secondary alcohol?

Other processes stated in this thread are good, I'm sure, but it's been a goal of mine to use easier to get reagents.  Most mentioned up to date are difficult to obtain.  I could, however, be wrong about that fact.
Who wants to play cops and dope fiends?

[ztion]

I think that by terminal alcohol he meant a primary alcohol. Generally when you oxidize such an alcohol it overoxidizes to the carboxylic acid. As far as I know the only way to oxidize such an alcohol to the aldehyde is with PCC. (Or if the aldehydes boiling point is lower than the alcohol, destilling it out before it can be oxidized further). It would be really useful to be able to oxidize for example phenethylalcohol to phenylacetaldehyd without the expensive PCC.

[Moriarty]

Actually that's interesting and clears a lot up for me.  This was also a major point of one source I read, however, not really to be a concern as 1-phenyl-2-propanol is a secondary alcohol, is it not?  We're not really trying to produce a aldehyde here as one might think if he or she were to read about the Fenton specifically.  This reaction was originally performed with primaries in mind, but H2O2 is great for secondaries as well.  Secondaries will not form aldehydes or carboxyls in the presence of an oxygen source, to my knowledge, they should form ketones.  Which is what we want.  Quoting an old high school chemistry book, "The middle [2 position] carbon in 2-propanol has an oxidation number of 0.  In propanone, it has an oxidation number of +2, an increase of 2.  Hence, 2-propanol is being oxidized to propanone", Chemistry: The Study of Matter, 1983, Allyn and Bacon, p. 613.  Sorry to bust out the high school chem, but that's all I had on hand.  It would be impossible to form aldehydes or carboxyl groups, which generlly form out of aldehydes.  Thanks for the help.  I now understand what was being said and would like to amend my answer to say yes, it is a legitimate concern with primaries, but not with 1-phenyl-2-propanol.
Who wants to play cops and dope fiends?

[Aurelius]

aurelius was simply concerned with the oxidation of Phenethanol to its aldehyde and/or ethanol to acetaldehyde.  However, the chemistry you proposed is an interesting read.  thanks for taking the time to answer aurelius' question.  Chromates and Pyridine aren't in short supply around here, aurelius just wanted to find a green method.

[ChemicalSolution]

In this paper Julia has, these folks boast about NOT over-oxidizing the terminal OH to COOH.

1-phenyl-propan-2-ol your SWIM asks??

These folks oxidize C6H5CHOHCH3 as well as C6H5CHOHC6H6 to their respective ketones in yields of 85% or greater... Will it work on 1-phenyl-propan-2-ol???  Julia thinks so...

xoxo
Julia

[ChemicalSolution]

Now, SWIM is all about the theoretical.. But just where in the HELL is your SWIM going to get 1-phenyl-propan-2-ol ?

Want to try a Grignard with Benzyl chloride or (gasp) benzyl bromide with acetaldehyde???  Be SWIM's guest.

Now, here we are with a Markovnikof hydration of allylbenzene followed by oxidation to ketone..   Sure makes the O2 Wacker of allylbenzene seem much, much less troublesome..

[Prdy2GO]

Question: This makes P2P?
" 10g dichromate is disolved in 100g DMSO.  Benzyl alcohol (5.4g) is added.  Concentrated H2SO4 is added dropwise while keeping the temerature below 70C.   The reaction mixture is heated at 70C for an additional 30 min(somewheres in here the reaction mixture turnes dark green).

The reaction mixture is poured on ice and extracted with 3x100 portions of (DCM).  The organic layer is washed once with bi-carb (take advice from Julia-- do this in a beaker.. Otherwise you may blow the stopper off your sep funnel).  And again with water.

The paper uses et2O to extract this..  SWIM has done this extraction with both DCM and toluene.  Both have advantages and disadvantages--- DCM sometimes forms emulsions that take a while to seperate..  DCM can also carry DMSO with it--  this is usually not a problem with toluene..

I dont believe it...
Can it be that simple? Then WTF is everyone  else doing it the hard way?
Yields-- 85%"
85% of what the BzOH?
Thanks




Don't look at me I didn't do it!

[foxy2]

If you post a procedure Please post the details of the reference it came from.  Journal, year, issue, page ect

Thanks
Foxy
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[Rhodium]

Prdy2GO: The procedure you describe is probably an oxidation of benzyl alcohol to benzaldehyde. As it is run under anhydrous conditions, I believe that overoxidation to benzoic acid does not take place.

[Moriarty]

Okay.  I just priced some at some place I found at chemfinder.  Bad idea.  100 grams is worth more than the honey made from it.  Not really, but it's in the thousands.  I'm sure you could buy it with little suspicion, but who would want to.  Discussion is pretty much a mute point now.
Who wants to play cops and dope fiends?

[Rhodium]

Phenyl-2-propanol is easily made from PhMgBr and propylene oxide. Very cheap, all industrial reagents.

[Moriarty]

Retraction!
Who wants to play cops and dope fiends?

[foxy2]

Synthesis of 4,5-dimethylchrysene.    
Newman, Melvin S.   
J. Am. Chem. Soc.  (1940),  62  2295-300. 
Abstract
Details are given of the prepn. of o-MeC6H4CH2OH in 42% yield from PhCH2Cl and trioxymethylene or in 55% yield from o-MeC6H4MgBr; SOCl2 gives 89% of o-MeC6H4CH2Cl; NaCN in dil. EtOH gives 86% of o-MeC6H4CH2CN (I).  PhMgBr and propylene oxide give 60% of PhCH2CHMeOH which with PBr3 yields 63% of PhCH2CHMeBr (II).

Retentive Friedel-Crafts alkylation of benzene with optically active 2-chloro-1-phenylpropane and 1-chloro-2-phenylpropane.    
Masuda, Shinji; Nakajima, Tadashi; Suga, Sohei.   
Bull. Chem. Soc. Jpn.  (1983),  56(4),  1089-94. (In English)

They prepare 1-phenyl-2-propanol from propylene oxide and benzene.

Process for production of 1-phenyl-2-propanol.    
Mamedov, Markaz K.; Gusejnov, Vidadi M.  (USSR).   
U.S.S.R.  (1992),  SU  1778109   Patent in Russian.
Abstract
PhCH2CHMeOH prodn. by adding C6H6 to propylene oxide (I) in the presence of AlCl3 at 5-6° and passing an inert gas through the reaction mixt. was improved to increase the yield and improved the product quality by carrying out the process with 5-6:3:1 C6H6-I-AlCl3 and by using 2 L/min He as the inert gas.

Patent US5223633

This has some complex method of making 1-phenyl-2-propanol which is probably more applicable to more valuable products.


Grignard reactions of phenyloxirane in the presence of titanium tetraisopropoxide.    
Sosnovskii, G. M.; Astapovich, I. V.  
Zh. Org. Khim.  (1992),  28(7),  1377-9.
Abstract
The title reactions gave PhCHXCH2OH (X = Cl, Br, iodo) and HOCHPhCH2I in £90% combined yield after 20 min, and 65-80% PhCH2CHROH (R = Me, Et, Ph) after 6 h.(They are reacting with grignard reagents)

More to come....
Foxy


Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[foxy2]

This should work, although the yeild doesn't seem to bee stellar.
Foxy

Patent US4396627

5. 1-(4-Acetylphenyl) propan-2-one

Chromic acid solution (11.5 ml, made by adding sulphuric acid [7.3 ml] to sodium dichromate [10.0 g] in water [30 ml]  and making up to 50 ml with water) was added to a vigorously stirred solution of 1-(4-acetylphenyl) propan-2-ol (3.8 g) in ether (50 ml) keeping between 25 DEG-30 DEG. The mixture was stirred at ambient temperature for 2 hours, the organic phase was separated, washed with sodium bicarbonate solution and with saturated sodium chloride solution. The dried (MgSO4) solution was evaporated and distilled (2.5 g). b.p. 122 DEG-128 DEG/0.1 mm.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[foxy2]

A one pot synthesis unsymmetric secondary alcohols from two grignard reagents
Daniel L. Comins, and William Dernel
Tetrahedron Letters 22(12) 1981 pgs 1085-1088 

Sunnnary: The sequential addition of two Grignard reagents to 2-(N-methyl-N-formyl)-amino-pyridine(1) in tetrahydrofuran provides a high yield one pot synthesis of unsymmetrical
secondary alcohols.

The reaction is easily carried out by adding the first Grignard reagent (1.0 equiv./THF) to a solution of MFAP (1) in tetrahydrofuran at 0'. After a few minutes the second Grignard reagent (1.3 equiv.) is added and the reaction mixture is heated at reflux for 3 hours and then quenched (aqueous 10% HCl). After isolation and purification, good to high yields of sec-alcohols are obtained as indicated in the table.

First Grignard - PhCH2MgCl
Second Grignard - MeMgCl
Yeild 1-phenyl-2-propanol = 73%
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[karel]

What a nice work appeared in Tetrahedron Letters!

Catalytic aerobic oxidation of alcohols by Fe(NO3)3–FeBr3

Abstract: Selective aerobic oxidation of secondary and benzylic alcohols was efficiently accomplished by the binary catalyst system Fe(NO3)3–FeBr3 under air at room temperature. The oxidation developed in mild conditions and showed good yields. A secondary alcohol even in the presence of a primary one was selectively oxidized.

General procedure: Oxidation reactions catalyzed by Fe(NO3)3 –FeBr3 . A typical experiment was carried out in an open reaction tube provided with a condenser. To the mixture of Fe(NO3 )3·9H2 O (0.1 mmol) and FeBr3 (0.05 mmol) in 5 mL of CH3CN menthol was added (1 mmol). The reaction mixture was stirred under aerial conditions at room temperature. GC was used to follow the reaction. When the reaction was complete, CH2Cl2 was added and the two phases were separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with water, dried over MgSO4, and the solvent was removed in vacuo. The residue was chromatographed on a silica gel (70–270 mesh ASTM) column, and eluted with ethyl acetate/hexanes using various ratios. All products identified were found to be identical to authentic samples.

Authors used eight aliphatic secondary alcohols and benzyl alcohol with >75% yield.

TL 2002, 4475-4479