Chromium(VI) Oxide-3,5-Dimethylpyrazole


[1333-82-0]  · CrO3  · Chromium(VI) Oxide-3,5-Dimethylpyrazole  · (MW 99.99) (C5H8N2)

[67-51-6]  · C5H8N2  · Chromium(VI) Oxide-3,5-Dimethylpyrazole  · (MW 96.13)

(oxidizing agent for alcohols;1 oxidant for saturated carbons a to unsaturation2-5)

Physical Data: see Chromium(VI) Oxide.

Solubility: sol dichloromethane; slightly sol ether and pentane.

Form Supplied in: formed in situ from widely available reagents.

Preparative Method: drying of the CrO3 over P2O5 is recommended; rapid addition of DMP (1 equiv) to a suspension of chromium(VI) oxide (1 equiv) in dry CH2Cl2 (-20 °C) results in a dark red homogeneous solution after 10 min; the solution is then treated with the organic substrate (0.05-0.5 equiv).1,2

Handling, Storage, and Precautions: chromium salts are carcinogenic; this reagent should be used in a fume hood.

Oxidation of Alcohols.

The oxidation of primary and secondary alcohols is typically effected by treating the alcohol (1 equiv) with CrO3.DMP (1-10 equiv) at rt (eqs 1-3).1 Notably similar to Pyridinium Chlorochromate (PCC), the title reagent system has been shown to oxidize primary alcohols to aldehydes efficiently (eq 2). The ease of oxidation of both equatorial and axial alcohols using this complex has been demonstrated (eq 3); the reactions of both are complete within 40 min when stirred at room temperature. The authors suggest the intermediacy of a cyclic chromate ester species through which rapid intramolecular oxidation may occur.1

Oxidation of Unsaturated Alcohols.1

Allylic, benzylic, and propargyl alcohols readily interact with CrO3.DMP to provide the expected carbonyl compounds in good to excellent yield. Allylic alcohols can be oxidized with little or no competing oxidation of allylic methylene positions within the same molecule (eqs 4 and 5).

Benzylic alcohols are oxidized with comparable efficiency and the reaction is not sensitive to the electronic nature of the aromatic ring (eqs 6 and 7). Propargyl alcohols with both internal and terminal triple bonds are oxidized in good yield using CrO3.DMP (eq 8).

Oxidation of Saturated Allylic and Benzylic Carbons.

The CrO3.DMP complex appears to offer two unique advantages over PCC: an empty Lewis acidic coordination site on chromium, and an internal basic nitrogen that may aid in cleavage of a carbon-hydrogen bond.2 As a result, for allylic and benzylic oxidations, CrO3.DMP is superior to more conventional chromium oxidants which often suffer from low yields, practical complications, and/or inconvenient and extended reaction times. In the total synthesis of (±)-carpesiolin, CrO3.DMP was used to install an enone from an alkene precursor (eq 9).3 It was used once more for a similar transformation in the total synthesis of (-)-retigeranic A and several of its derivatives, where it was found to be the most efficient reagent for the purpose (eq 10).4

Observations made in the course of studies toward the synthesis of D5-7-keto steroids provide some insight into the mechanism of CrO3.DMP-mediated allylic oxidation.2 Here, axial hydrogens were found to be predisposed to more facile cleavage by this reagent, a common observation with chromium oxidants. The allylic oxidation of cholesteryl benzoate was complete within 30 min when CrO3.DMP was used in 20-fold excess. Alternatively, use of only a 12-fold excess of CrO3.DMP provided 74% conversion following stirring for 4 h at 0 °C. Benzylic methylenes are also susceptible to oxidation by this reagent.5

1. Corey, E. J.; Fleet, G. W. J. TL 1973, 4459.
2. Salmond, W. G.; Barta, M. A.; Havens, J. L. JOC 1978, 43, 2057.
3. Kok, P.; DeClercq, P. J.; Vandewalle, M. E. JOC 1979, 44, 4553.
4. (a) Paquette, L. A.; Wright, J.; Drtina, G. J.; Roberts, R. A. JOC 1987, 52, 2960. (b) Wright, J.; Drtina, G. J.; Roberts, R. A.; Paquette, L. A. JACS 1988, 110, 5806.
5. McDonald, E.; Suksamrarn, A. TL 1975, 4425.

Jeffrey N. Johnston

The Ohio State University, Columbus, OH, USA

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