(Hive Bee)
10-12-02 06:49
No 367667
      Oxidation of P2Pol - a literature search
(Rated as: excellent)

I've been curious about alkene to P2Pol to P2P for some time now. I'm aware that the real issue is the formation of the P2Pol from an allylbenzene without use of Hg, but here is what i've dug up. Hopefully these will be of some use/interest. I intend to look into P2Pol formation when i have more time, but there is a bit in TFSE including and alternatives to alkene starting material Post 310648 (Chemikaze: "Translation", Russian HyperLab)

(I've weeded out most of the lower yielding refs.)

Oxidation of alcohols by (NH4)2Cr2O7 in solution and under solvent-free conditions.
Shirini, F.; Zolfigol, M. A.; Mallakpour, B.; Mallakpour, S. E.; Hajipour, A. R.   Department of Chemistry, College of Science,  Guilan University,  Rasht,  Iran.   
Australian Journal of Chemistry  (2001), 54(6), 405-406 

Here they oxidize P2Pol to P2P in 10 minutes with a 90% yield. (Benzyl alcohol is also oxidized to benzaldehyde 5 min, 92% yield, solvent free, or 95% yield with solvent).

The oxidation of various alcohols was investigated using (NH4)2Cr2O7 in the presence of Mg(HSO4)2 and wet SiO2 (Scheme 1), at room temperature. Yields and reaction times are given in table 1. Over oxidation of the products, using this method, was not observed
Scheme 1:
(i) (NH4)2Cr2O7 /Mg(HSO4)2/wet SiO2, solvent free, room temperature.
(ii) (NH4)2Cr2O7 /Mg(HSO4)2/wet SiO2, n-hexane, room temperature.
Substrate: 1-phenylpropan-2-ol
Product: phenylpropan-2-one
Solvent free oxidation (i): Time 10 min, yield 90%
Oxidation in solvent (ii): Time 300 min, yield (mixture)

The omission of the solvent not only eases the workup, but reduces the reaction time. This method is not suitable for the oxidation of allylic alcohols (e.g. cinnamyl alcohol).
It should be noted that the oxidation did not proceed using any of Mg(HSO4, ammonium dichromate or wet SiO2 alone. These results could be attributed to the in situ generation of H2CrO4 in low concentration at the surface of wet SiO2 by the solid inorganic salts (Mg(HSO4)2 and (NH4)2Cr2O7.
The authors note that this method is attractive for large-scale operations
Oxidation of Benzyl Alcohol to bezaldehyde under solvent free conditions: a typical procedure.
To a mixture of Mg(HSO4)2 (0.654 g, 3mmol), wet SiO2 (50% w/w, 0.1 g) and (NH4)2Cr2O7 (0.126 g, 0.5 mmol), was added benzyl alcohol (0.108 g, 1 mmol). The resultant mixture was shaken at room temperature for 3 minutes. The progress of the reaction was monitored by TLC. The reaction mixture was triturated with CH2Cl2 (10mL) and then filtered. Anhydrous MgSO4 was aadded to the filtrate and the mixture filtered after 10 min. Evaporation of the solvent followed by column chromatography on silica gel gave the benzaldehyde in 92% yield.

A mild and efficient oxidation of alcohols with N-tert-butylphenylsulfinimidoyl chloride in the coexistence of zinc oxide.  
Matsuo, Jun-Ichi; Kitagawa, Hideo; Iida, Daisuke; Mukaiyama, Teruaki.    Department of Applied Chemistry, Faculty of Science,  Science University of Tokyo,  Tokyo,  Japan.   
Chemistry Letters  (2001),(2), 150-151.  

P2Pol is oxidized to P2P in 66% yields using N-tert-butylphenylsulfinimidoyl chloride in the presence of ZnO. The conditions for P2Pol to P2P are given as room temperature, 30 min.

Experimental (typical procedure):
To a stirred white suspension of 2 (2-phenylethanol, 70 mg, 0.0.57) and zinc oxide (233 mg, 2.86 mmol) in dry CH2Cl2 (1.5mL) was added a solution of 1 (N-tert-butylphenylsulfinimidoyl chloride, 185 mg, 0.86 mmol) in CH2Cl2 (2mL) at 0C. The reaction mixture was stirred for 30 min at the same temperature and then quenched with water (5mL). The mixture was filtered through Celite and the filter cake was washed with CH2Cl2 and water. The layer were separated and the aqueous phase was extracted with CH2Cl2. The yield of 3 (phenylacetaldehyde, 0.52 mmol, 91%) was determined by GC analyses of the combined organic phase using an internal standard.

Table 1: Effect of bases

Entry   Base                Yield% (phenylacealdehyde)
3       MS4A (1g/mmol)      73 (56)b
6       MgO (10 eq.)        58
7       CaO (5 eq.)         56
8       BaO  (5 eq.)        70
12      ZnO (5eq)           91 (35)c  (0)d
b 3 g/mmol used, c ZnO (2 eq) used, d N-tert-butylphenylsulfinimidoyl chloride was not used
MS = molecular sieves

Notes:  in order to prevent decomposition of the formed carbonyl product, the oxidation using N-tert-butylphenylsulfinimidoyl chloride must be conducted under as neutral conditions as possible. Therefore, the original procedure was changed by replacing DBU with another suitable scavenger of HCl, which was liberated during the formation of an intermediate, alkoxysulfilimine, from N-tert-butylphenylsulfinimidoyl chloride and an alcohol. Then it was thought that an insoluble solid base would be suitable because it would not cause decomposition of the formed carbonyl  compounds.

Oxidation process of alcohols using periodic acid and chromium catalyst.
Tschane, David M.; Song, Zhiguo; Zhao, Mangzu.  (Merck and Co., Inc., USA).    PCT Int. Appl.  (1999), 28 pp. 
WO9952850 Patent WO9952850
Also the equivalent:
A Novel Chromium Trioxide Catalysed Oxidation of Primary Alcohols to the Carboxylic Acids
Zhao, M. Li, J.  Song, z.  Desmond, R.  Tschaen D.M.  Grabowski E.J.J. and Reider P.J.
Tetrahedron letters 39 (1998) 5323 5326.
(also see Post 107446 (Acme: "A new oxidation for MDP2-ol?", Methods Discourse))
P2Pol is oxidized to P2P in 98% yields using periodic acid and chromium trioxide.
Also phenylethanol to phenylacetic acid (96%)

Since strong acids enhance the oxidation potential of CrO3, H2SO4 was added to the reaction mixture. This appeared to improve the oxidation slightly. On the other hand, water had a dramatic effect on the reaction rate. By eliminating water from the system, complete reation occurred in less than 15 minutes at room temperature. Subsequently, we found that the presence of small amounts of water attenuated the oxidation strength of the system and provided cleaner reactions. Thus the best yields can be obtained by adding a solution of H5IO6/CrO3 (2.5 equiv./1.1 mol % *) in wet MeCN (0.75 v % water) to the alcohols at 0 5 [deg] C. The reactions were typically complete within one hour. It should be noted that no reaction was observed in the absence of chromium trioxide. Substituting periodic acid with other oxidants (H2O2, t-BuO2H, AcO2H etc without TsOH) was unsuccessful. For unknown reasons the reaction also failed to give the desired product when carried out in acetone.
Typical procedure: A stock solution of H5IO6/CrO3 was prepared by dissolving of H5IO6 (11.4 g, 50 mmol) and CrO3 (23 mg, 1.2 mol %) in wet MeCN (0.75 v % water) to a volume of 114 mL (complete dissolution typically required 1-2 hours). The H5IO6/CrO3 solution (11.4 mL) was then added to a solution of the alcohol 1 (2.0 mmol) in wet MeCN (10 mL, 0.75 v water) in 30-60 minutes while maintaining the reaction temperature at 0-5 [deg]. The mixture was aged at 0C for 0.5 h and the completion of the reaction was confirmed by HPLC assay. The reaction was quenched by adding an aqueous solution of Na2HPO4 (0.60 g in 10 mL water). Toluene (15 mL) was added and the organic layer was separated and washed with 1/1 brine/water mixture (2 x 10mL) then a mixture of aqueous NaHSO3 (0.22 g in 5 mL water) and finally brine (5 mL). The organic layer was then concentrated to give the crude carboxylic acid 2. Most of the crude products were quite pure based on 1H NMR and HPLC assay.

* Only 1.25 equivalents of periodic acid and 0.6 mol % CrO3 are required for secondary alcohol to ketone.

Substrate: P2Pol
Product: P2P
Temp/H5IO6/CrO3: 0/1.25/0.6
Yield: 98%

Substrate: Phenethanol
Product: phenylacetic acid
Temp/H5IO6/CrO3: 0/2.5/1.1
Yield: 96%

Stereoselective oxidation and reduction by immobilized Geotrichum candidum in an organic solvent. 
Nakamura, Kaoru; Inoue, Yuko; Matsuda, Tomoko; Misawa, Ibuki.    Institute for Chemical Research,  Kyoto University,  Uji, Kyoto,  Japan.   
Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry  (1999),(16), 2397-2402. 

P2P is formed in 44% yield from P2Pol

Cells of the fungus, Geotrichum candidum, were immobilized on a water-absorbing polymer and used for stereoselective oxidn. and redn. in an org. solvent using cyclohexanone, cyclopentanol or 2-alkanols as additive.  Enantiomerically pure (R)-1-arylethanols were obtained by the stereoselective oxidn. of racemic 1-arylethanols, whereas enantiomerically pure (S )-1-arylethanols were obtained by the redn. of the corresponding ketones, in contrast to redn. in water by the free cells in which (R)- or (S )-1-arylethanols were produced in low ee.  The reaction mechanism was investigated by measuring the partition of the substrates and products between the org. phase and aq. phase in the polymer around which the cells were immobilized.  Deuterated compds. were used to det. the role of the additives.

Homochiral (R)- and (S)-1-heteroaryl- and 1-aryl-2-propanols via microbial redox.
Fogagnolo, Marco; Giovannini, Pier Paolo; Guerrini, Alessandra; Medici, Alessandro; Pedrini, Paola; Colombi, Nicola.  Dipartimento di Chimica,  Universita di Ferrara,  Ferrara,  Italy.
Tetrahedron: Asymmetry  (1998), 9(13), 2317-2327. 

Trifluoromethyl-P2P is formed from trifluoromethyl-P2Pol in 43% yields

Prepn. of various heteroaryl propanols and of the corresponding propanones as starting materials for microbial redox was described.  The kinetic resoln. of the racemic propanols was achieved via oxidn. with Pseudomonas paucimobilis and Bacillus stearothermophilus [(R)-alcs., ee 74-100%].  Similar results are achieved with 3-(2-hydroxypropyl)trifluoromethylbenzene.  The redn. of the propanones with baker's yeast and other fungi gave (S)-alcs. (ee 100%).  The pure (S)-alcs. were also obtained by redn. of 1-[3-(trifluoromethyl)phenyl]-2-propanone.  1-[(4,4-Dimethyl)-2-(D2)oxazolinyl]-2-propanone and 1[2-(D2)-thiazolinyl]-2-propanone were not reduced.803.  The heterocyclic rings of (S)-5-(2-hydroxypropyl)-3-methylisoxazole and of (S)-2-(2-hydroxypropyl)-4-methylthiazole were deblocked to a homochiral enamino ketone (78%) and to a protected b-hydroxy aldehyde (73%), resp.  Also, (R)-3-(2-hydroxypropyl)trifluoromethylbenzene was transformed into a homochiral precursor of (S)-fenfluramine (overall yield 65%).

Oxidation of alcohols by silica gel-supported bis(trimethylsilyl) chromate.
Lee, Jong Gun; Lee, Jung A.; Sohn, Soo Yun.  College Natural Sciences,  Pusan National Univ.,  Pusan,  S. Korea.   
Synthetic Communications  (1996), 26(3), 543-9. 

P2P is formed in 91% yield from P2Pol

Chromium oxidants absorbed on solid supports such as PCC on alumina, chromic acid on silica and chromyl chloride on silica-alumina are reported as giving better yields under milder conditions, than the corresponding parent oxidants. Herein we report that BTSC (bis(trimethylsilyl) chromate) supported on chromatographic grade silica gel is very efficient for the oxidation of alcohols of various types to the corresponding carbonyl compounds.  Heating chromic anhydride with a slight excess of hexamethyldisiloxane in carbon tetrachloride produces a nearly homogenous solution. BTSC supported on silica gel was conveniently prepared simply by adding silica gel into the vigorously stirred pre-made solution. The dark brown free-flowing solid was obtained on evaporation of volatile materials. It can be stored in a dark brown bottle without appreciable loss of reactivity for at least 3 months.
The oxidation reactions were carried out simply by adding  1 2 equivalents of BTSC supported on silica gel to the stirring solution of an alcohol in CH2Cl2.
[Yields are significantly higher than reactions not supported]

Alcohol: 1-phenyl-2-propanol
Temperature: 40C
Time: 30 min.
Product: phenylacetone
Yield: 91%

Alcohol: cyclohexanol
Temperature: 25C
Time: 15 min.
Product: cyclohexanone
Yield: 99%

Preparation of bis(trimethylsilyl) chromate supported on silica gel: Into a solution of hexamethyldidiloxane (64mL, 0.3 mol) in 200mL  of carbon tetrachloride was added chromic anhydride (30g, 0.3 mol). The reaction mixture was stirred in a 50C bath for 5 hours. Solid chromic anhydride dissolved and the dark red mixture became a homogenous solution. Silica gel (130 g) pre-dried in a 120C oven overnight was added into the warm reaction mixture and the resulting mixture was stirred further for 5 hours. The solvent and other volatile components were distilled off under reduced pressure to afford 193 g of supported chromium oxidant. The calculated 1.54 mmol per gram of this typical batch of the reagent was regarded as the effective chromium concentration.

Oxidation of cyclohexanone: Silica gel suppored bis(trimethylsilyl) chromate (0.8 g, equivalent to 1.2 mmol of chromium (VI) oxidant) was placed in a round bottem flask and covered with 5mL of CH2Cl2. Into the stirring mixture was added cyclohexanol (105 mg, 1.04 mmol). After 10 minutes of stirring the reaction mixture was gravity filtered and washed with 10mL of ether or CH2Cl2. Evaporation of the solvent gave 101 mg of cyclohexanone (99%) of which GC analysis showed negligible amounts of impurities.

Asymmetric synthesis of (S)-4,5-difluoro-2-methylindoline.
Tsuji, Koichi; Ishikawa, Hiroshi. Microbiological Res. Inst.,  Otsuka Pharm. Co. Ltd.,  Tokushima,  Japan.   
Synthetic Communications  (1994), 24(20), 2943-53. 

Ketone from alcohol: CrO3/H2SO4 99% yield.

N-[(S)-N-p-Tolylsulfonyl]prolinyl-2-(2-oxo)propyl-3,4-difluoroanilide   (4a):
A solution of CrO3 (0.75g, 7.5 mmol) in 30% aqueous H2SO4 (2mL) was added to a stirred solution of the anilide 3a (3.95 g, 0.009 mol) in acetone (36mL) and the resulting mixture was stirred 45 min at room temperature. After addition of i-PrOH (0.84 mL, 0.011 mol), the mixture was filtered and the filtrate was evaporated. The residue was dissolved in a mixture of CH2Cl2 and water. The aqueous phase was extracted twice with CH2Cl2 and the combined organic extracts were washed twice with water, then dried over MgSO4. Evaporation of the solvent afforded ketone 4a (3.89 g, 99%) as a brown solid, which was used in the next step without further purification.

Got democracy?
(Chief Bee)
10-12-02 11:20
No 367709
      Phenyl-2-propanol  Bookmark   

Nice! For the synthesis of P2Pol without the use of Hg, these may be worth looking into:

* Bull. Chem. Soc. Jpn. (1983),  56(4),  1089-94. (In English)
  1-phenyl-2-propanol from propylene oxide and benzene.

* Patent US 5223633
  Complex method of making 1-phenyl-2-propanol which is probably not useful.

* Grignard reactions of phenyloxirane in the presence of titanium tetraisopropoxide.    
  Zh. Org. Khim.  (1992),  28(7),  1377-9.
  65-80% P2Pol from Styrene epoxide

* 1-Phenyl-2-propanol from phenylmagnesium bromide and propylene oxide
  JACS 62, 2295-2300 (1940)

To a Grignard reagent prepared from 471g of bromobenzene and 74g of magnesium in 1400 cc. of ether as slowly added 180g of propylene oxide. After refluxing for 20h, the mixture was treated with ammonium chloride solution. The crude product (bp 90-110C/14 mm), amounted to 280g. On fractionation there was obtained 244g (60%) of 1-Phenyl-2-propanol, bp 105.5-107.0C/14-15mmHg.

(Hive Bee)
01-10-03 16:29
No 397081
      Grignard reactions of phenyloxirane in the...  Bookmark   

Grignard reactions of phenyloxirane in the presence of titanium tetraisopropoxide.    
  Zh. Org. Khim.  (1992),  28(7),  1377-9.
  65-80% P2Pol from Styrene epoxide

I 've asked our Russian friends to look up this article and translate the experimental section.  And you know what, this reaction is great smile: Post 396757 (Fomalhaut: ", , ...", Russian HyperLab)
(Chief Bee)
01-10-03 18:53
No 397122
      Very slick P2P!  Bookmark   

Wonderful! I have HTMLized it and put it here: ../rhodium /p2pol.styrenepoxide.html

It seems like MeMgI gives rise to allylbenzene iodohydrin in 90% yield, and treatment of that with K2CO3 will very easily form allylbenzene epoxide, which in turn can be isomerized to P2P in high yield with LiI, if the isomerization doesn't happen spontaneously anyway... If LiOH or Li2CO3 is used as the base, LiI will form in situ from the HI liberated from the iodohydrin, and a one-pot P2P preparation is a fact.
(Hive Bee)
05-20-03 12:28
No 434379
      To generate P2P from the P2Pol, one could use...  Bookmark   

To generate P2P from the P2Pol, one could use one of the variants of the Swern oxidation:

Patent US3901896