Copper(II) Bromide

CuBr2

[7789-45-9]  · Br2Cu  · Copper(II) Bromide  · (MW 223.36)

(brominating agent; oxidizing agent; Lewis acid)

Alternate Name: cupric bromide.

Physical Data: mp 498 °C; d 4.770 g cm-3.

Solubility: very sol water; sol acetone, ammonia, alcohol; practically insol benzene, Et2O, conc H2SO4.

Form Supplied in: almost black solid crystals or crystalline powder; also supplied as reagent adsorbed on alumina (approx. 30 wt % CuBr2 on alumina).

Purification: recryst from H2O and dried in vacuo.35

Handling, Storage, and Precautions: anhydrous reagent is hygroscopic and should therefore be stored in the absence of moisture.

a-Bromination of Carbonyls.

Copper(II) bromide is an efficient reagent for the selective bromination of methylenes adjacent to carbonyl functional groups.1 Thus 2-hydroxyacetophenone treated with a heterogeneous mixture of CuBr2 in CHCl3-EtOAc gives complete conversion to 2-bromo-2-hydroxyacetophenone with no aromatic ring bromination (eq 1).2

Similar selectivity is obtained with a homogeneous solution of the reagent in dioxane.3 A limitation of the reaction is observed with 2-hydroxy-4,6-dimethoxyacetophenone, which undergoes aromatic nuclear bromination with CuBr2.4 Steroidal ketones have been selectively a-brominated with CuBr2 in the presence of a double bond without bromination of the alkene (eq 2),5 while g-bromination occurs in other steroidal enones.1

Copper(II) bromide has been used to a-brominate diketotetraquinanes6 and to introduce a double bond into a prostanoid nucleus in a one-pot bromination-elimination procedure (eq 3).7 3,7-Dibromo-2H,6H-benzodithiophene-2,6-diones (eq 4)8 and 5-bromo-4-oxo-4,5,6,7-tetrahydroindoles (eq 5)9 are prepared by the selective a-bromination of their respective ketone starting materials without bromination of the aromatic or heterocyclic rings. 4-Carboxyoxazolines are converted to the corresponding oxazoles using a mixture of CuBr2 and 1,8-Diazabicyclo[5.4.0]undec-7-ene (eq 6).10

Bromination of Alkenes and Alkynes.

Heating copper(II) bromide in methanol with compounds containing nonaromatic carbon-carbon multiple bonds leads to di- or tribromination.11 For example, under these conditions allyl alcohol is converted to 1,2-dibromo-3-hydroxypropane in 99% yield (eq 7), while propargyl alcohol produces a mixture of trans di- and tribromoallyl alcohols (eq 8). 2-Hydroxy-5-methyl-4-methoxychalcone undergoes a bromination-ring-closure reaction, affording 3-bromo-6-methyl-5-methoxyflavanone when heated with CuBr2 in refluxing dioxane (eq 9).12 The mechanism of the bromination of cyclohexene to 1,2-dibromocyclohexane with CuBr2 has been studied.13

Bromination of Aromatics.

Aromatic systems are brominated by copper(II) bromide. For example, 9-bromoanthracene is prepared in high yield by heating anthracene and the reagent in carbon tetrachloride (eq 10).14 When the 9-position is blocked by a halogen, alkyl, or aryl group, the corresponding 10-bromoanthracene is formed.15 Under similar conditions, 9-acylanthracenes give 9-acyl-10-bromoanthracenes as the predominant products.16 The aromatic nuclear bromination of monoalkylbenzenes has been shown to proceed cleanly under strictly anhydrous conditions (eq 11).17a Polymethylbenzenes are efficiently and selectively converted to the nuclear brominated derivatives by CuBr2/Alumina.17b In the absence of alumina, a mixture of products resulting from benzylic halogenation is isolated. 3-Acetylpyrroles are nuclear monobrominated at the 4-position in high yield by CuBr2 in acetonitrile at ambient temperature (eq 12).18 The reaction also proceeds with ethyl 3-pyrrolecarboxylates to give 4-bromopyrrole derivatives,19 while an excess of brominating agent at 60 °C affords 4,5-dibromopyrroles.20

Bromination of Allylic Alcohols.

Silica gel-supported copper(II) bromide has been used for the regioselective bromination of methyl 3-hydroxy-2-methylenepropanoates and 3-hydroxy-2-methylenepropanenitriles (eq 13).21a In the absence of silica gel, no reaction occurs between CuBr2 and these substrates, while adsorption onto Al2O3, MgO, or TiO2 leads to side reactions rather than the clean allylic bromination observed with CuBr2/SiO2. The reaction is stereoselective with respect to formation of the (Z) isomer.

Benzylic Bromination.

Toluene and substituted methylbenzenes undergo benzylic bromination using CuBr2 and t-Butyl Hydroperoxide in acetic acid or anhydride (eq 14).21b While the yields (43-95%) are not quite as high as those obtained using N-Bromosuccinimide, the copper(II) bromide procedure allows the benzylic bromination of compounds which are insoluble in nonpolar solvents.

Esterification Catalyst.

Highly sterically hindered esters are prepared by the reaction of S-2-pyridyl thioates and alcohols in acetonitrile with copper(II) bromide as the catalyst.22 The reaction proceeds at ambient temperature under mild conditions and affords high yields of a range of sterically crowded esters such as t-butyl 1-adamantanecarboxylate (eq 15).

Conjugate Addition Catalyst.

The 1,4-addition of Grignard reagents to a,b-unsaturated esters is promoted by catalytic CuBr2 (1-5 mol%) with Chlorotrimethylsilane/HMPA (eq 16).23 Under these conditions the copper(II) species is not reduced by the Grignard reagent, resulting in high yields of the conjugate addition products.

Oxidation of Stannanes and Alcohols.

Allylstannanes have been oxidized with copper(II) bromide in the presence of various nucleophilic reagents (H2O, ROH, AcONa, RNH2) to afford the corresponding allylic alcohols, ethers, acetates, and amines.24 This chemistry has been extended to trimethylsilyl enol ethers, which undergo a CuBr2-induced carbon-carbon bond forming process with allylstannanes (eq 17).25 Alkoxytributylstannanes may be converted to the corresponding aldehyde or ketone with two equivalents of CuBr2/Lithium Bromide in THF at ambient temperature (path a, eq 18).26 A combination of copper(II) bromide/Lithium t-Butoxide oxidizes alcohols to carbonyl compounds quite rapidly and in high yield (path b, eq 18).27

Desilylbromination.

b-Silyl ketones are desilylbrominated to a,b-unsaturated ketones with CuBr2 in DMF.28 This occurs spontaneously in cyclic ketones, while with open-chain ketones sodium bicarbonate is required to eliminate HBr from the b-bromo ketone thus formed. The carbon-silicon bond in organopentafluorosilicates prepared from alkenes and alkynes is cleaved with copper(II) bromide to give the corresponding alkyl and alkenyl bromides (eq 19).29 The reaction is stereoselective; thus (E)-alkenyl bromides are obtained from (E)-alkenylsilicates.

Reagent in the Sandmeyer and Meerwein Reactions.

Diazonium salts of arylamines are converted to aryl halides (Sandmeyer reaction)30 in the presence of copper(II) halides. Recent procedures have utilized t-butyl nitrite/CuBr231 or t-butyl thionitrite/CuBr232 combinations to afford aryl bromides from the corresponding arylamines in high yields (eq 20). The copper salt-catalyzed haloarylation of alkenes with arenediazonium salts (Meerwein reaction) also proceeds with copper(II) halides. For example, treatment of p-aminoacetophenone with t-butyl nitrite/CuBr2 in the presence of excess acrylic acid gives p-acetyl-a-bromohydrocinnamic acid (59% yield, eq 21).33 The intramolecular version of this reaction, which affords halogenated dihydrobenzofurans, has been accomplished by reacting arenediazonium tetrafluoroborates with CuBr2 in DMSO (eq 22).34

Related Reagents.

Bromine; N-Bromosuccinimide; Copper(I) Bromide.


1. (a) FF 1967, 1, 161. (b) Bauer, D. P.; Macomber, R. S. JOC 1975, 40, 1990.
2. King, L. C.; Ostrum, G. K. JOC 1964, 29, 3459.
3. Doifode, K. B.; Marathey, M. G. JOC 1964, 29, 2025.
4. Jemison, R. W. AJC 1968, 21, 217.
5. Glazier, E. R. JOC 1962, 27, 4397.
6. Paquette, L. A.; Branan, B. M.; Rogers, R. D. T 1992, 48, 297.
7. Miller, D. D.; Moorthy, K. B.; Hamada, A. TL 1983, 24, 555.
8. Nakatsuka, M.; Nakasuji, K.; Murata, I.; Watanabe, I.; Saito, G.; Enoki, T.; Inokuchi, H. CL 1983, 905.
9. Matsumoto, M.; Ishida, Y.; Watanabe, N. H 1985, 23, 165.
10. Barrish, J. C.; Singh, J.; Spergel, S. H.; Han, W.-C.; Kissick, T. P.; Kronenthal, D. R.; Mueller, R. H. JOC 1993, 58, 4494.
11. Castro, C. E.; Gaughan, E. J.; Owsley, D. C. JOC 1965, 30, 587.
12. Doifode, K. B. JOC 1962, 27, 2665.
13. Koyano, T. BCJ 1971, 44, 1158.
14. (a) See Ref. 1a, p 162. (b) Mosnaim, D.; Nonhebel, D. C. T 1969, 25, 1591.
15. Mosnaim, D.; Nonhebel, D. C.; Russell, J. A. T 1969, 25, 3485.
16. Nonhebel, D. C.; Russell, J. A. T 1970, 26, 2781.
17. (a) Kovacic, P.; Davis, K. E. JACS 1964, 86, 427. (b) Kodomari, M.; Satoh, H.; Yoshitomi, S. BCJ 1988, 61, 4149.
18. Petruso, S.; Caronna, S.; Sprio, V. JHC 1990, 27, 1209.
19. Petruso, S.; Caronna, S.; Sferlazzo, M.; Sprio, V. JHC 1990, 27, 1277.
20. Petruso, S.; Caronna, S.; JHC 1992, 29, 355.
21. (a) Gruiec, A.; Foucaud, A.; Moinet, C. NJC 1991, 15, 943. (b) Chaintreau, A.; Adrian, G.; Couturier, D. SC 1981, 11, 669.
22. Kim, S.; Lee, J. I. JOC 1984, 49, 1712.
23. Sakata, H.; Aoki, Y.; Kuwajima, I. TL 1990, 31, 1161.
24. Takeda, T.; Inoue, T.; Fujiwara, T. CL 1988, 985.
25. Takeda, T.; Ogawa, S.; Koyama, M.; Kato, T.; Fujiwara, T. CL 1989, 1257.
26. Yamaguchi, J.; Takeda, T. CL 1992, 423.
27. Yamaguchi, J.; Yamamoto, S.; Takeda, T. CL 1992, 1185.
28. (a) FF 1989, 14, 100. (b) FF 1980, 8, 196.
29. Yoshida, J.; Tamao, K.; Kakui, T.; Kurita, A.; Murata, M.; Yamada, K.; Kumada, M. OM 1982, 1, 369.
30. Dickerman, S. C.; DeSouza, D. J.; Jacobson, N. JOC 1969, 34, 710.
31. Doyle, M. P.; Siegfried, B.; Dellaria, J. F. JOC 1977, 42, 2426.
32. Oae, S.; Shinhama, K.; Kim, Y. H. BCJ 1980, 53, 1065.
33. Doyle, M. P.; Siegfried, B.; Elliott, R. C.; Dellaria, J. F. JOC 1977, 42, 2431.
34. Meijs, G. F.; Beckwith, A. L. J. JACS 1986, 108, 5890.
35. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 321.

Nicholas D. P. Cosford

SIBIA, La Jolla, CA, USA



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