Dipyridine Chromium(VI) Oxide1

[26412-88-4]  · C10H10CrN2O3  · Dipyridine Chromium(VI) Oxide  · (MW 258.22)

(reagent for oxidizing alcohols to carbonyl compounds)

Alternate Names: Collins reagent; chromium(VI) oxide-pyridine.

Solubility: sol CH2Cl2; (Z)-1,2-dichloroethylene; pyridine; CHCl3.

Form Supplied in: red crystals; not commercially available.

Preparative Methods: prepared in 85-91% yield from Chromium(VI) Oxide and Pyridine.2,3 Caution: the reaction is extremely exothermic. The chromium(VI) oxide should be added to dry pyridine at such a rate that the temperature does not exceed 20 °C and in such a way that the oxide mixes rapidly with pyridine. Other chromium(VI) oxide-pyridine complexes are known. These include the Ratcliffe reagent (dipyridine chromium(VI) oxide prepared in situ in CH2Cl2),4,5 and the Sarett reagent (CrO3.(C5H5N)2 in pyridine).6 The preparation and workup of the Sarett reagent is sometimes tedious. The hygroscopic nature of the Collins reagent and its propensity to inflame may be avoided by the in situ preparation of the complex according to the Ratcliffe procedure.

Handling, Storage, and Precautions: Caution: the Collins reagent is extremely hygroscopic; exposure to moisture rapidly converts it to the yellow dipyridinium dichromate. The reagent should be stored at 0 °C under nitrogen or argon in a sealed container, protected from light. All chromium(VI) reagents must be handled with care; their mutagenicity is well documented.7 This reagent should be prepared and handled in a fume hood.

Allylic Oxidation to Form a,b-Unsaturated Ketones.

Although a solution of chromium(VI) oxide in pyridine is not very useful for allylic oxidation, the isolated dry chromium(VI) oxide-dipyridine complex in dichloromethane oxidizes allylic methylene groups to enones at rt in good to excellent yields. D5-Androsten-7-one-3b,17b-diol diacetate is thus obtained (82%) from the oxidation of D5-androstene-3b,17b-diacetate.8 Attack at an allylic methine position yields the isomeric enone when possible; for example, 3-(4-fluorophenyl)cyclohexenol is oxidized to the isomeric enone (eq 1).8 Similar rearrangements occur in methylene systems with steric hindrance.8 If more than one allylic methylene group is present in a conformationally flexible molecule, isomeric enones resulting from attack at both positions are formed (eq 2).8 Selectivity is observed in conformationally rigid molecules.8 Methyl groups are not easily oxidized. In general, the Collins reagent gives higher yields and less overoxidation than Di-t-butyl Chromate or Chromium(VI) Oxide in acetic acid.

Alkynes are oxidized to conjugated alkynic ketones (ynones) by the Collins reagent.9 The Collins reagent oxidizes 4-octyne to 4-octyn-3-one (eq 3). Oxidation of alkynes by t-Butyl Hydroperoxide and catalytic amounts of Selenium(IV) Oxide10 effects oxidation at both centers adjacent to a triple bond. A catalytic amount of chromium(VI) oxide in benzene and t-butyl hydroperoxide selectively oxidizes alkynes to ynones in about 50% yield.11

Oxidation of Primary Alcohols to Aldehydes.

The oxidation of alcohols is generally performed in dichloromethane with a sixfold excess of the Collins reagent. The Collins reagent3 gives higher yields than the Sarett reagent6 and comparable yields to the Ratcliffe reagent.5 The Collins reagent oxidizes 1-heptanol to 1-heptanal in 70-84% yield3 and the Ratcliffe reagent oxidizes 1-decanol to 1-decanal in 83% yield.4,5 The Collins reagent oxidizes the primary allylic alcohols geraniol (eq 4) and nerol (eq 5) to geranial and neral, respectively, without isomerization.12 The Ratcliffe reagent oxidizes cinnamyl alcohol to cinnamaldehyde in 96% yield.5 The Collins reagent has been used to oxidize primary hydroxy groups of sugars to aldehydes in 50-75% yield.13 Although the Sarett reagent is useful for the conversion of primary allylic and benzylic alcohols to their corresponding aldehydes, its use for primary saturated alcohols (with the exception of some steroidal ones) is less effective than the Collins or Ratcliffe reagent.

The oxidation of allylic alcohols to aldehydes is facilitated by use of Celite-supported Collins reagent (eq 6).14,15 This method has been used to prepare intermediates in the synthesis of bulnesol14 and guaiol.15 A modified Ratcliffe reagent, CrO3.2py in acetonitrile on Celite, was used to oxidize primary alcohols to aldehydes.16

The (S)-alcohol (1) is oxidized by the Collins reagent to the aldehyde (2) with no more than 5% racemization (eq 7).17

Primary alcohols are converted to the corresponding t-butyl esters by Collins reagent in CH2Cl2/DMF/Ac2O and a large excess of t-butyl alcohol (eq 8).18 This conversion is probably general except for aromatic aldehydes.

Oxidation of Secondary Alcohols to Ketones.

The Collins reagent (eq 9),19 the Ratcliffe reagent,5 and the Sarett reagent20,21 are effective in oxidizing secondary alcohols to ketones. Generally, acid sensitive functional groups such as acetals, double bonds, oxiranes, and thioethers are not affected, although there are exceptions. The Collins reagent oxidizes exo-7-hydroxybicyclo[4.3.1]deca-2,4,8-triene to bicyclo[4.4.1]deca-2,4,8-triene-7-one (64%).22 Collins reagent oxidizes the secondary alcohol functional groups in b-hydroxy-(Z)-O-alkyloximes to the corresponding b-keto-O-alkyloximes.23

A number of alternative reagents are available for the oxidation of primary and secondary alcohols to aldehydes and ketones. Related chromium-based reagents include Chromium(VI) Oxide-3,5-Dimethylpyrazole, Chromium(VI) Oxide-Quinoline, Pyridinium Chlorochromate, and Pyridinium Dichromate.

Oxidation of Tertiary Allylic Alcohols to Epoxy Aldehydes.

The Collins reagent oxidizes tertiary allylic alcohols to epoxy aldehydes (eq 10).24

Oxidation of Carbohydrates.

Addition of acetic anhydride to the Collins reagent increases the yields (>90%) for the oxidation of secondary hydroxy groups to carbonyl groups in carbohydrates.13,25,26

Oxidation of b-Hydroxy Ketones to 1,3-Diketones.

Collins reagent oxidizes b-hydroxy ketones to 1,3-diketones (eq 11).26,27 Higher yields are generally obtained with Dimethyl Sulfoxide-Oxalyl Chloride (Swern reagent).

Oxidation of b-Hydroxy Esters to b-Keto Esters.

Collins reagent oxidizes b-hydroxy esters to b-keto esters (eq 12).27

Oxidative Cyclization of 5,6-Dihydroxyalkenes.

Collins reagent oxidizes the unsaturated diols (3) to the corresponding cis-tetrahydrofurandiols (4) (eq 13).28

Oxidation of 1,4-Dienes.

Oxidation of the 1,4-diene (5) with Collins reagent or Di-t-butyl Chromate yields dienones (6) and (7) in the ratio of 1:3 (~65% total yield) (eq 14).29 Complementary regioselectivity (6)/(7) = 9:1 (~70% total yield) is obtained with Pyridinium Chlorochromate (PCC).

Other Applications.

Collins reagent, Jones' reagent, and chromic acid in 50% acetic acid oxidatively deoximate ketoximes to the corresponding carbonyl compounds.30

Secondary alkylstannanes are converted into the corresponding carbonyl compounds by oxidation with Collins reagent (eq 15).31,32 Mixtures of alcohols and dehydration products are obtained from tertiary alkylstannanes.

Collins reagent oxidizes trimethylsiloxy-substituted 1,4-cyclohexadienes to phenols (eq 16).32

Collins reagent oxidizes steroidal tertiary amines to N-formyl derivatives (eq 17).3

1. (a) Wiberg, K. B. Oxidation in Organic Chemistry; Wiberg, K. B., Ed.; Academic: New York, 1965; Part A, pp 131-135. (b) Freeman, F. Organic Synthesis By Oxidation With Metal Compounds; Miijs, W. J.; de Jonge, C. R. H. I., Eds.; Plenum: New York, 1986; Chapter 2. (c) Lee, D. G. The Oxidation of Organic Compounds by Permanganate Ion and Hexavalent Chromium; Open Court: La Salle, IL, 1980. (d) Stewart, R. Oxidation Mechanisms: Applications to Organic Chemistry; Benjamin: New York, 1964. (e) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic Chemistry; Springer: Berlin, 1984.
2. Collins, J. C.; Hess, W. W. OSC 1988, 6, 644.
3. Collins, J. C.; Hess, W. W.; Frank, F. J. TL 1968, 3363.
4. Ratcliffe, R. W. OSC 1988, 6, 373.
5. Ratcliffe, R. W.; Rodehorst, R. JOC 1970, 35, 4000.
6. Poos, G. I.; Arth, G. E.; Beyler, R. E.; Sarett, L. H. JACS 1953, 75, 422.
7. Cupo, D. Y.; Wetterhahn, K. E. Cancer Res. 1985, 45, 1146 and references cited therein.
8. Dauben, W. G.; Lorber, M.; Fullerton, D. S. JOC 1969, 34, 3587.
9. Shaw, J. E.; Sherry, J. J. TL 1971, 4379.
10. Chabaud, B.; Sharpless, K. B. JOC 1979, 44, 4202.
11. Muzart, J.; Piva, O. TL 1988, 29, 2321.
12. Holum, J. R. JOC 1961, 26, 4814.
13. Butterworth, R. F.; Hanessian, S. S 1971, 70.
14. Andersen, N. H.; Uh, H. SC 1973, 3, 115.
15. Andersen, N. H.; Uh, H. TL 1973, 2079.
16. Schmitt, S. M.; Johnston, D. B. R.; Christensen, B. G. JOC 1980, 45, 1135, 1142.
17. Evans, D. A.; Bartroli, J. TL 1982, 23, 807.
18. Corey, E. J.; Samuelsson, B. JOC 1984, 49, 4735.
19. Gilbert, J. C.; Smith, K. R. JOC 1976, 41, 3883.
20. Urech, J.; Vischer, E.; Wettstein, A. HCA 1960, 43, 1077.
21. Ellis, B.; Petrow, V. JCS 1956, 4417.
22. Schröder, G.; Prange, U.; Putze, B.; Thio, J.; Oth, J. F. M. CB 1971, 104, 3406.
23. Shatzmiller, S.; Bahar, E.; Bercovici, S.; Cohen, A.; Verdoorn, G. S 1990, 502.
24. Sundararaman, P.; Herz, W. JOC 1977, 42, 813.
25. Garegg, P. J.; Samuelsson, B. Carbohydr. Res. 1978, 67, 267.
26. Samano, V.; Robins, M. J. S 1991, 283.
27. Smith, A. B. III.; Levenberg, P. A. S 1981, 567.
28. Walba, D. M.; Stoudt, G. S. TL 1982, 23, 727.
29. Wender, P. A.; Eissenstat, M. A.; Filosa, M. P. JACS 1979, 101, 2196.
30. Araújo, H. C.; Ferreira, G. A. L.; Mahajan, J. R. JCS(P1) 1974, 2257.
31. Still, W. C. JACS 1978, 100, 1481.
32. Still, W. C. JACS 1977, 99, 4836.

Fillmore Freeman

University of California, Irvine, CA, USA

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