Tetrahedron Letters No.

31, pp 2647 - 2650,

1975.

Pergamon Press.

Printed m Great Brltam.

PYRILVNHJM CHLOROCHROMATE. AN EFFICIENT REAGENT FOR OXIDATION OF PRIMARY AND SECONDARYALCOHOLS To CARRONYL COMWUNHS E. J. Corey and J. William Suggs Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138, USA (Beceived in USA 10 June 1975; received in UK for publication 19 June 1975)

pyridinium chlorochromate, C5H5NHCr03C1, a readily available, stable reagent, oxidizes a wide variety of alcohols to carbonyl compounds with high efficiency. It is easily and safely prepared by the

addition of pyridine to a solution of chromium Rioxide in 8 g HCl followed by filtration to obtain the yellow-orange, air-stable solid. Yields of aldehydes and ketones obtained with 1.5 molar equivalents are typically equal to or greater than those obtained with the Collins reagent (using the customary five- or six-fold excess). On the basis of the results obtained thus far tbis reagent obviously qualifies 2-7 as an important addition to the present methodology, particularly for moderate to large scale

oxidations.

In a typical small scale experiment pyridinium chlorochromate (1.5 mmol) was suspended in
methylene chloride @* room temperature. reduced reagent. 2 ml), and the alcohol (1 mmol in 0.5 to 1.5 ml of CH2C12)was rapidly added at The solution became briefly homogeneous before depositing the black insoluble

After 1-2 hours the oxidation. followed by either thin layer chromatography or vapor The black reaction mixture was diluted with 5 volumes of an-

phase chromatography, was complete. become granular).

hydrous ether, the solvent was decanted, and the black solid was washed twice with ether (causing it to product was isolated simply by filtration of the organic extracts through Florisil Use of more polar reaction solvents such as The and evaporation of the solvent at reducedpressure.

acetonitrile or acetone (in which the reagent is soluble) leads to inconveniently long reaction times. results of representative experiments are summarized in the table.

The slightly acidic character of the reagent can be modified by buffering the reaction mixture with powdered sodium acetate. survive. Ry thts expedient even such acid-labile groups as tetrahydropyranyl ethers The mildly acidic character of pyridinium chlorochromate has been used to advsntage in

essentially a one-flask synthesis of pulegone (III) from citronellol (I), as outlined below (12% overall yield). 8 The &y-unsaturated ketone II, which was the end product of oxidation, furnished pulegone after exposure to base.

2648

No. 31

Tablea Alcohol 1-Decanol 1,6-Hexanediol BellZllydrol 4-t_ Butylcyclohexanol act-I-yn-l-01 1-Heptanold Productb Decanal Hexanedial Benwphenone 4-t_Butylcyclohexanone Ott-2-y?.& Heptanal I neld 92 68 100 97 84 78

CHO

85

H3C R* A R

*. Q
I H H cH3

CH2OH Presqualene aldehyde 78

R = (CH3),C=CHCH2CH2C(CH3)=CHCH2CH2(Presqualene alcohol) Citronellole HOCH2CH%HCH20THPe Citronella1 CHOCH&HCH20THP 82 81

Unless otherwise indicated, oxidation was performed at 25 with l-2 mm01 of alcohol. b Products were characterized by comparison with authentic material (nmr and ir spectra, and thin layer or vapor phase chromatography). d All yields refer to isolated product. Performed with 0.1 mol of alcohol. eSodium acetate was added to buffer the reaction mixture; 2 equiv. of pyridinimn chlorochromate was used.

No. 31

2649

P
I
III The following Pyridinium ._ pyridine was used for the preparation of the reagent. 9 To 184 ml of 6 JvJHCl (1.1 mol) was added 100 g (1 mol) of CrO3 Chlorochromate. solution was cooled to 0 and 79.1 g (1 mol) of to 0 gave a yellow-orange solid which was The solid is not without change. Found: procedure
rapidly with stirring. After 5 min. the homogeneous

yas carefully on a sintered hygroscopic

added over 10 min.

Retooling

collected

glass funnel and dried for 1 hr -in vacua (yield 180.8 g, 84%). and can be stored for extended periods C, 27.83; H, 2.81; Cr, 24.15. a comparison N, 6.50; at room temperature Cl, 16.45;

appreciably Anal lo -* C, 27.95;

Calcd.

for C5H6N03ClCr: N, 6.31;

Cr, 24.13.

H, 2.83;

Cl, 16.65;

Heptanal was prepared reagent as described can be seen as clearly

with the use of Collins 11 Our procedure for the same case on a 0.05 mole scale in Organic Syntheses s more economical. and convenient agent). flask fitted with a reflux condenser CH2C12. was suspended 32.3 g than the Collins method (which uses 6 times as

on a 0.1 mole scale so as to facilitate

much solvent and 4 times as much oxidizing Heptanal. In a 500-ml round-bottomed

(150 mmol) of pyridinium

chlorochromate

in 200 ml of anhydrous

1-Heptanol solution.

(11.6 g, 100 After 1.5 hr residue

mmol) in 20 ml of CH2C12 was added in one portion to the magnetically 200 ml of dry ether was added and the supernatant was washed thoroughly 3 times with 50-ml portions granular solid. The combined organic

stirred

decanted from the black gum.

The insoluble

of anhydrous ether whereupon it became through a short pad of Florisil, oil through a short Vigreux identical

a black and the column 12

solution was passed Distillation

solvent was removed

by &stillation.

of the residual

gave 8.87 g (78%) of heptanal,

bpgO 59-61;

ir and nmr spectra the procedure

with authentic material. reagent.

A final example is given to illustrate Citronellal. Pyridimum

used with the acetate-buffered

chlorochromate

(1.23 g, 5.7 mmol) and sodium acetate CH2ClZ and citronellol stirred

(0.093 g, 1.14

mmol) were suspended in 5 ml of anhydrous CH2C12 was added in one portion worked up as described

(0.59 g, 3.8 mmol) in 5 ml of After 2 hr the reaction Column chromatography ir and nmr spectra was on silica with

to the magnetically

solution.

above to yield 0.523 g of crude citronellal. pure by vpc and tic analysis;

gel gave 0.479 g (82%) of citronellal, authenlac material.

identical

2650

1. J. C. Collins, 2.

W. W. Hess,

and F. J, Frank,

Tetrahedron&, s

3363 (1968). Tetrahedron m,

E. J. Corey and C. U. Kim, 2. Amer. -919 (1973); -9 idem Tetrahedron @. J Se -* m., -

Chem. m..

7586 (1972); idem, C. U. Kim,

E, 1233 (1973); E. J. Corey,

E., 4499 (1973).

and M. Takeda,

, 4339 (1972). Tetrahedron m., =, 39

3. 4. 5. 6.

E. J. Corey and G. W. J. Fleet, Y. S. Rao and R. Filler, K. E. Pfitzner K. Bowden, A. Bowers, J* a0

3304 (1974). Chem. E., 8& 5661 (1965); E, 1762 (1966). 39 (1946);

and J. G. Moffatt,

2. -Amer.

I. M. Heilbron, T. G. Halsall,

E. R. H. Jones, E. R. H. Jones,

and B. C. L. Weedon, and A. J. Lemin, a,

J0 Chem. e., 2555 (1951). B. A. Hems,

7.

J. Attenburrow, Jensen,

A. F. B, Cameron, J__ Chem. &.,

J, H. Chapman, 1104 (1952).

R. M. Evans,

A. B. A.

and T. Walker,

8. Work in collaboration 9. For other preparations

with H. E. Ensley to be published see J. Bernard and M. Camelot, 2. Anorg. Algem.

separately. C_. I& Acad. m, Paris, 258, 5881 N. Y.

(1964); R. J. Meyer and H. Best, 10. 11. 12. Microanalysis J. C. Collins was performed and W. W. Hess,

Chem.,

2& 197 (1899). Laboratory, Woodside,

by Schwarzkopf a0 S-v&, g,

Microanalytical 5 (1972).

This work was assisted

financially

by a grant from the Nationai Science

Foundation.