Chromium(II) Acetate


[14976-80-8]  · C4H8CrO5  · Chromium(II) Acetate  · (MW 188.12)

(capable of reducing reactive carbon-halogen bonds (e.g. allylic, benzylic, a-halo carbonyl);1 bromohydrins2 and epoxides;3 used in the conversion of ketoximes to ketones4 in the presence of acid- and base-sensitive functional groups)

Physical Data: d 1.79 g cm-3.

Solubility: slightly sol cold water; readily sol hot water; sol in and reacts with most acids; slightly sol alcohol; practically insol ether.

Form Supplied in: deep red powder or monoclinic crystals; composed of dimeric units. Drying: loses water when dried over P2O5 at 100 °C, changing color to brown.

Handling, Storage, and Precautions: easily oxidized, especially when moist, to chromium(III) acetate. It can be stored for several months in a stoppered vial under carbon dioxide.

Reduction of Carbon-Halogen Bonds.

2a,4a-Dibromocholestan-3-one (1) has been reduced to 4a-bromocholestan-3-one (2) in 97% yield5 (recrystallization afforded 78% yield) when treated with a large excess of freshly prepared chromium(II) acetate in acetic acid for 10 min (eq 1). On the other hand, with the theoretical amount of reagent the yield was only 20%.6

Reduction of 4-bromoisophorone (3) with chromium(II) acetate gives b-phorone (4) as the major product;7 isophorone (5) is obtained as a minor product (eq 2). The reagent is freshly prepared by treatment of CrCl3.6H2O with amalgamated zinc and then with sodium acetate.

In the construction of the ring A system of some of the giberellins,8 iodolactone (6) has been reduced following the method developed by Barton and co-workers (eq 3).2,9 Chromium(II) ion in DMSO is used in the presence of ethanethiol. The reaction occurs with inversion to give the cis-fused decalin system (7) (presumably through a radical mechanism).8 A variety of conditions (irradiation, catalytic hydrogenation) are useless for the deiodination.

1,2,3,4,7,7-Hexachloro-5-endo-acetoxybicyclo[2.2.1]-2-heptene (8) is reduced by refluxing with chromium(II) acetate in acetic acid for 16 h to furnish (9) in 78% yield in which the chlorine atom anti to the double bond is mainly replaced (eq 4).10 With zinc-acetic acid the reduction is not so clean since four products are formed. Reaction with Palladium on Carbon leads to reduction and dechlorination of the vinyl system.

Reduction of Bromohydrins.2,9

Treatment of 9a-bromo-11b-hydroxyprogesterone (11) with chromium(II) acetate (5 equiv) in DMSO containing butane-1-thiol (7.5 equiv) gives 11b-hydroxyprogesterone (12) in 80% yield (eq 5).11 Similarly, 9a-bromocortisol-21-acetate,12 9a-bromoprednisolone-21-acetate,13 and 17,20:20,21-bismethylenedioxy-9a-bromocortisol14 afford cortisol-21-acetate (78%), prednisolone-21-acetate (74%) and 17,20:20,21-bismethylenedioxycortisol (80%), respectively. In the absence of butane-1-thiol the reduction proceeds in a different manner. The bromohydrin gives 5,9-cyclo-11b-hydroxypregnane-3,20-dione (13) (58%).

According to Barton et al.2,9 the chromium(II) ion reduction of a bromohydrin (14) would proceed in two stages as shown in (eq 6). Thus a radical intermediate (15) would be the first product of reduction. Further reduction of this radical would furnish the anion (16), which by elimination would give the normal product (17) of bromohydrin reduction. The radical (15) could, in principle, be captured by a ready transfer donor of radical hydrogens such as butanethiol with the formation of (18). The BuS&bdot; radical will dimerize to (BuS)2 (19).

Reductive Cleavage of an Epoxide.

The 16a,17a-epoxy steroid (20) is converted by chromium(II) acetate into the b-hydroxy ketone (21) and the unsaturated ketone (22) (eq 7).15

In a study of potential routes to the A/B ring system of cardiac active steroids (periplogenin, strophanthidin) Robinson and Henderson3 studied the reduction of 4b,5b-oxidocholestan-3-one (23) with chromium(II) acetate. The best results were obtained by reduction of (23) with a large excess of freshly prepared chromium(II) acetate in aqueous acetone. In this case the desired product (24) could be obtained in about 50% yield (eq 8). The minor product (25) can be recycled.

Conversion of Ketoximes to Ketones.

The method involves the conversion of an oxime to the O-acetate derivative, followed by reaction with >2 mol equiv of chromium(II) acetate in 9:1 THF-water (by weight) at a temperature between 25 °C and 65 °C. Chromium(II) acetate causes reductive fission of the oxime N-O linkage to give an imine which will rapidly hydrolyze to a ketone. This method is highly effective even in the presence of acid- and base-sensitive functional groups, such as acetals, hemithioacetals, esters, and epoxides. It is noteworthy that the reaction occurs more readily with acetoximes of conjugated ketones than with those of nonconjugated ketones, and that the reaction ocurs readily with acetoximes of hindered ketones such as camphor. The reaction has been used in a three-step conversion of alkenes into ketones. For example, Nitrosyl Chloride is added to cyclooctene (26) and the resulting 2-chlorocyclooctanone oxime (27)16 is then acetylated and treated with chromium(II) acetate at 65 °C for 16 h. Cyclooctanone (28) is obtained in 88% yield (eq 9).

The reaction also has been used for transposition of a carbonyl group. Oxidation of propiophenone (29), followed by reduction with Sodium Borohydride and acetylation, gives the a-acetoxy acetoxime (30) which on treatment with excess chromium(II) acetate affords phenyl acetone (31) (eq 10).

In an asymmetric synthesis of 19-norsteroids, Pappo et al.17 cleaved (32) and (33) to (34) and (35), respectively (eq 11), in high yield using chromium(II) acetate in aqueous THF (16 h, 30-40 °C). The methyl esters of (32) and (33) were not cleaved. Hence the presence of a carbonyl group in close proximity to the N-O bond is essential for this reaction.

1. (a) Castro, C. E.; Kray, Jr., W. C. JACS 1963, 85, 2768; 1964, 86, 4603. (b) Kochi, J. K.; Davis, D. D. JACS 1964, 86, 5264. (c) Slaugh, L. H.; Raley, J. H. T 1964, 20, 1005. (d) Kochi, J. K.; Singleton, D. M. JACS 1967, 89, 6547.
2. Barton, D. H. R.; Basu, N. K.; Hesse, R. H.; Morehouse, F. S.; Pechet, M. M. JACS 1966, 88, 3016.
3. Robinson, C. H.; Henderson, R. JOC 1972, 37, 565.
4. Corey, E. J.; Richman, J. E. JACS 1970, 92, 5276.
5. Williamson, K. L.; Johnson, W. S. JOC 1961, 26, 4563.
6. Evans, R. M.; Hamlet, J. C.; Hunt, J. S.; Jones, P. G.; Long, A. G.; Oughton, J. F.; Stephenson, L.; Walkers, T.; Wilson, B. M. JCS 1956, 4356.
7. Marx, J. N. Org. Prep. Proc. Int., 1973, 5, 45.
8. Bachi, M. D.; Epstein, J. W.; Herzberg-Minzly, Y.; Lowenthal, H. J. E. JOC 1969, 34, 126.
9. Barton, D. H. R.; Basu, N. K. TL 1964, 3151.
10. Williamson, K. L.; Hsu, Y. F. L.; Young, E. I. T 1968, 24, 6007.
11. (a) Reichstein, T.; Fuchs, H. G. HCA 1940, 23, 684. (b) Rosenkranz, G.; Pataki, J.; Djerassi, C. JOC 1952, 17, 290.
12. (a) Fried, J.; Herz, J. E.; Sabo, E. F.; Borman, A; Singeo, F. M.; Numerof, P. JACS 1955, 77, 1068. (b) Nishikawa, M.; Noguchi, S. Yakugaku Zasshi 1958, 78, 213.
13. Fried, J.; Florey, K.; Sabo, E. F.; Herz, J. E.; Restiro, A. R.; Borman, A; Singers, F. M. JACS 1955, 77, 4181.
14. Akhtar, M.; Barton, D. H. R.; Beaton, J. M.; Hortmann, A. G. JACS 1963, 85, 1512.
15. Schwarz, V. CCC 1961, 26, 1207.
16. Ohno, M.; Naruse, N.; Terasawa, I. OS 1969, 49, 27.
17. Pappo, R.; Garland, R. B.; Jung, C. J.; Nicholson, R. T. TL 1973, 1827.

Tapan Ray

Sandoz Research Institute, East Hanover, NJ, USA

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