Copper Chromite1

[12053-18-8]  · Cr2Cu2O5  · Copper Chromite  · (MW 311.10)

(hydrogenation catalyst for many functional groups;3 decarboxylation;4 dehydrogenation5)

Alternate Name: Adkins or Lazier catalyst.2

Solubility: insol organic solvents; practically insol water and dilute acids; reactions are typically carried out in ethanol, dioxane, ether, methylcyclohexane or without solvent.

Form Supplied in: fine black powder; the best catalysts contain ca. 10% barium oxide.

Preparative Methods: although commercially available, the original preparations are often referenced in the literature.6

Handling, Storage, and Precautions: stable to air and moisture; care should be taken to avoid skin contact and inhalation since chromium and barium compounds are highly toxic.

Hydrogenation.1

The main use of copper chromite is as a hydrogenation catalyst, especially in the reduction of oxygen-containing functionality. The reactions are generally carried out at high temperatures (100-300 °C) and high pressures (40-375 atm compressed at rt), limiting the catalyst's use to robust and/or lightly functionalized molecules. Many of the possible functional group reductions may be easier to carry out using metal hydrides such as Lithium Aluminum Hydride or Sodium Borohydride under milder conditions. However, the yields of copper chromite-catalyzed hydrogenations are often high and may be well suited to large scale preparations of simple intermediates.

At the high temperatures involved in the hydrogenations, side reactions with solvent need to be considered; ethanol, for example, can behave as an alkylating agent of amines, amides may undergo alcoholysis, and esters transesterification. Consequently it may be advantageous to perform some reactions neat.

Carbonyl Compounds.

Aldehydes and ketones are amongst the easiest functional groups to hydrogenate, giving primary and secondary alcohols, respectively. However, at higher temperatures further reduction to the hydrocarbons may occur if the alcoholic product is activated in some way (eq 1).7 Alkenes in the molecule may also be reduced under the reaction conditions.8 A study of the competitive hydrogenation of aldehydes, ketones, and alkenes has been published9 and alkene reduction in the presence of cyclopropyl rings has also been reported.10 The cis and trans stereoisomers from the reduction of 2-hydroxycyclodecanone have been separated by fractional crystallization (eq 2).11

The hydrogenation of esters yields the expected primary alcohols and this reaction has been reviewed.12 Lactones give the corresponding diols (eq 3).13 Alkenes in the molecule will also be reduced14 but amides may be left intact since they generally require much higher temperatures before reduction takes place (eq 4).15

Amides16 will react at high temperature (usually above 200 °C) and pressure to give amines (eq 5).17 Nitro groups also give amines.3 Glutaramides have been shown to cyclize to piperidines upon reduction18 and indolizidines have been prepared in a similar way (eq 6).19 Nitriles react when carbonyl groups are present in the same molecule to give cyclic amines20 and lactams (eq 7).21

Aromatic Compounds.

In some cases, selective hydrogenation of aromatic nuclei can be achieved. Saturation of the 9,10-double bond of phenanthrene is possible with careful monitoring of the hydrogen uptake to prevent over-reduction.22 Heteroaromatics are also partially reduced over copper chromite, where Raney Nickel is unselective (eq 8).23 At 300 °C, total reduction of 2-methyl-2,3-dihydrobenzofuran to propylcyclohexane was observed in 96% yield.24

Hydrogenolysis.

Amines can be hydrogenolyzed to the corresponding methyl compounds (eq 9),25 as can the benzyl alcohols.26 Some cyclic ethers also show carbon-oxygen bond cleavage (eq 10).27

Decarboxylation of Aromatic Compounds.

Copper chromite has been used, usually in the presence of Quinoline, as a decarboxylating reagent for aromatic compounds. Yields can be high for simple substrates4 and a decarboxylation-aromatization has been reported (eq 11).28 Some fairly sensitive molecules can survive the reaction conditions, including nitrile pyrroles29 and isothiazoles (eq 12).30 Copper chromite-catalyzed hydrogenation of o-acylbenzoic acid to o-ethylbenzoic acid was accomplished by first forming the sodium salt.31 See also Copper Chromite-Quinoline.

Dehydrogenation of Alcohols.

A few examples of copper chromite acting as a dehydrogenating agent are known.32 Alcohols can be oxidized to ketones (eq 13)5 and diols to lactones, presumably via the lactols (eq 14).33 Dehydration following dehydrogenation has also been observed (eq 15).34 Copper chromite can be activated prior to use in hydrogenation reactions by heating at reflux in cyclohexanol for 4 h, during which time cyclohexanone is formed.5

Other Reactions.

More unusual reactions mediated by copper chromite include carbon-carbon bond hydrogenolysis (eq 16);35 oxidation of a carbon-hydrogen bond a to a ketone;36 a ring contraction to give thiophenes (eq 17);37 and a one pot conversion of b-amino alcohols to a-methyl ketones (eq 18),38 a reaction which proceeds mechanistically via alcohol dehydrogenation, amine elimination, and resultant double bond hydrogenation.


1. Grundmann, C. In Newer Methods of Preparative Organic Chemistry; Wiley: New York, 1948; pp 103-123.
2. Fieser, L.; Fieser, M. FF, 1969, 2, 82.
3. Adkins, H.; Connor, R. JACS 1931, 53, 1091.
4. Cook, J. W.; Schoental, R. JCS 1945, 288.
5. Nes, W. R. JOC 1958, 23, 899.
6. (a) Adkins, H.; Burgoyne, E. E.; Schneider, H. J. JACS 1950, 72, 1091. (b) Lazier, W. A.; Arnold, H. R. OSC 1943, 2, 142.
7. Reeve, W.; Sterling, J. D., Jr. JACS 1949, 71, 3657.
8. Alder, K.; Krieger, H.; Weiss, H. CB 1955, 88, 144 (CA 1956, 50, 5596g).
9. Jenck, J.; Germain, J.-E. J. Catal. 1980, 65, 141.
10. Slabey, V. N.; Wise, P. A. JACS 1952, 74, 3887.
11. Blomquist, A. T.; Goldstein, A. OSC 1963, 4, 216.
12. (a) Adkins, H. OR 1954, 8, 1. (b) Adkins, H.; Folkers, K. JACS 1931, 53, 1095.
13. Christian, R. V., Jr.; Brown, H. D.; Hixon, R. M. JACS 1947, 69, 1961.
14. Cason, J.; Pippen, E. L.; Taylor, P. B.; Winans, W. R. JOC 1950, 15, 135.
15. Segel, E. JACS 1952, 74, 851.
16. McElevain, S. M.; Pryde, E. H. JACS 1949, 71, 326.
17. Cronyn, M. W. JOC 1949, 14, 1013.
18. Paden, J. H.; Adkins, H. JACS 1936, 58, 2487.
19. Tsuda, K.; Saeki, S. JOC 1958, 23, 91.
20. (a) Barr, W.; Cook, J. W. JCS 1945, 438. (b) Badger, G. M.; Cook, J. W.; Donald, G. M. S. JCS 1951, 1392.
21. Gates, M.; Webb, W. G. JACS 1958, 80, 1186.
22. Phillips, D. D. OSC 1963, 4, 313.
23. (a) Adkins, H.; Coonradt, H. L. JACS 1941, 63, 1563. For partial reduction of isoquinoline see (b) Leonard, N. J.; Leubner, G. W. JACS 1949, 71, 3408.
24. Entel, J.; Ruof, C. H.; Howard, H. C. JACS 1951, 73, 4152.
25. Reeve, W.; Sadle, A. JACS 1950, 72, 3252.
26. (a) Emerson, W. S.; Heider, R. L.; Longley, R. I., Jr.; Shafer, T. C. JACS 1950, 72, 5314. (b) Huber, W. F.; Renoll, M.; Rossow, A. G.; Mowry, D. T. JACS 1946, 68, 1109.
27. Kaufman, D.; Reeve, W. OSC 1955, 3, 693.
28. Da Settimo, A.; Primofiore, G.; Livi, O.; Ferrarini, P. L.; Spinelli, S. JHC 1979, 16, 169.
29. Anderson, H. J.; Loader, C. E. S 1985, 353.
30. Grant, M. S.; Pain, D. L.; Slack, R. JCS 1965, 3842.
31. Elsner, B. B.; Struass, H. E.; Forbes, E. J. JCS 1957, 578.
32. Nanavati, D. D. J. Indian Chem. Soc. 1974, 51, 551 (CA 1974, 81, 119 860t).
33. Longley, R. I., Jr.; Emerson, W. S. OSC 1963, 4, 677.
34. Summerbell, R. K.; Jerina, D. M.; Grula, R. J. JOC 1962, 27, 4433.
35. Frank, R. L.; Berry, R. E. JACS 1950, 72, 2985.
36. Igarashi, K.; Mori, Y.; Takeda, K. Steroids 1969, 13, 627.
37. Campaigne, E. JACS 1944, 66, 684.
38. Sirokman, G.; Molnar, A.; Bartok, M. Appl. Catal. 1983, 7, 133 (CA 1984, 100, 51 127n).

David E. Cladingboel

Fisons Pharmaceuticals, Loughborough, UK



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