Copper(I) Chloride-Oxygen1

CuCl-O2
(CuCl)

[7758-89-6]  · ClCu  · Copper(I) Chloride-Oxygen  · (MW 99.00) (O2)

[7782-44-7]  · O2  · Copper(I) Chloride-Oxygen  · (MW 32.00)

(oxidation of alcohols,2 amines,6 alkenes;7 oxidative coupling;1 allylic oxidation;9 oxidative cleavage;1 oxidative dealkylation;22 Ullmann reaction23)

Physical Data: see Copper(I) Chloride.

Solubility: sol ether, HCl, TMEDA, and NH4OH; sl sol cold water; insol alcohol and nonpolar solvents.

Form Supplied in: O2 is widely available as cylinders of compressed gas. CuCl is also commercially available.

Handling, Storage, and Precautions: strong oxidant. Appropriate precautions for handling of combustible compressed gases should be taken. Use in a fume hood.

Oxidation of Alcohols.

Various oxidation systems have been used to synthesize aldehydes from alcohols. In the presence of Copper(I) Chloride in pyridine, alcohols can be oxidized by molecular Oxygen to give aldehydes or ketones.2 High yields of aldehydes or ketones are obtained when 1,10-phenanthroline is used instead of pyridine (eq 1). Under this CuCl/amine/O2 system, 1,10-phenanthroline is more effective and allows benzylic and allylic alcohols to be oxidized much faster than aliphatic alcohols.3

In the presence of a catalytic mixture of copper(I) chloride and the radical reagent 2,2,6,6-Tetramethylpiperidin-1-oxyl (TEMPO), secondary alcohols are preferred over primary alcohols in their oxidation by oxygen to yield the corresponding ketones. Overoxidation is not observed, as benzylic and allylic alcohols yield aldehydes (eqs 2 and 3). However, electron-withdrawing groups attached to the aryl ring in benzylic alcohols tend to retard the reaction.4

An oxidation system composed of a transition metal (M0 = Fe0 or Cu0), a transition metal ion (Mn+Cln = FeCl2 or CuCl) in catalytic amounts, and molecular oxygen oxidizes (hydroxymethyl)phenols to give the corresponding salicylaldehydes (eq 4).5

Oxidation of Phenols.

Selectivity in copper-amine catalyzed phenol oxidations is controlled by a number of factors: substituent effects, solvent effects, and stability of phenoxy radicals. Oxidative coupling of 2,6-disubstituted phenols occurs in two ways, depending on the size of the substituent group on the benzene ring. When the substituent groups are small, carbon-oxygen coupling occurs and poly-2,6-disubstituted 1,4-phenylene ethers (2) are obtained. However, the presence of bulky groups allows the synthesis of 3,3,5,5-tetrasubstituted diphenoquinones (3) to occur through carbon-carbon coupling (eq 5).6

Selective phenol oxidation by oxygen may occur, depending on the type of solvent used. Synthesis of t-butyl-p-benzoquinone from t-butyl hydroquinones (eq 6) occurs in the presence of copper(I) chloride in pyridine, whereas 2-t-butyl-6-hydroxy-p-benzoquinone is synthesized in the presence of copper(I) chloride in a secondary amine such as piperidine, morpholine, dipropylamine, or 2,6-dimethylpiperidine (eq 7).7

Regarding stability of the phenoxy radical, selectivity can be achieved in the oxidation of 2,6-diphenyl-4-methoxyphenol by oxygen in the presence of copper(I) chloride (eq 8). The resulting product would be a dimeric quinone acetal (or 4-methoxy-2,6-diphenylphenoxyl) in high yield, obtained through an oxygen-stable radical.8

Oxidation of Amines.

Under an oxygen atmosphere, copper(I) chloride in pyridine converts amines to the corresponding nitriles (eq 9) or aldehydes (eq 10).9 However, low yields prompted the modification of this reaction system by (a) increasing the reaction temperature (from rt to 60 °C), (b) adding molecular sieves, and (c) changing the order of addition of the reactants. This improved, extended method gives high yields of aliphatic or aromatic nitriles (eq 11).10

Oxidation of Alkenes.

In the presence of a catalyst, copper(I) chloride, and Palladium(II) Chloride in aqueous DMF, terminal alkenes are oxidized by oxygen to methyl ketones (eq 12).11

Allylic Oxidation.

Synthesis of a,b-unsaturated ketones via copper-catalyzed allylic oxidation is possible. In the presence of copper(I) chloride, valencene was oxidized by molecular oxygen in the dark to nootkatone (eq 13). Iron(II) Sulfate, NiSO4, ZnSO4, Copper(II) Sulfate and MnSO4 are among other catalysts that have been used in allylic oxidation under an oxygen atmosphere.12

Oxidative Cleavage of Diols.

A copper-catalyzed oxidation system involving oxygen/copper(I) chloride in a mixture of pyridine and alcohol is able to cleave catechols to monoesters of cis,cis-muconic acid (eq 14).13

Oxidative Cleavage of Hydrazones.

Alkynes can be synthesized in high yields from dihydrazones of a-diketones via oxidation under an oxygen atmosphere in the presence of copper(I) chloride in pyridine at room temperature (eq 15). The monohydrazone of benzil can be dehydrogenated to produce azibenzil in high yield (eq 16).14

Oxidative Cleavage of Diamines and Diketones.

Various oxidizing reagents, for example Nickel(II) Peroxide, Lead(IV) Acetate, and Silver(I) Oxide in stoichiometric quantities, have limited effectiveness in the oxidation of these substrates, producing less than 50% yields of the projected oxygenation products. However, under an oxygen atmosphere, o-phenylenediamine undergoes oxidative cleavage in the presence of copper(I) chloride in pyridine to yield cis,cis-mucononitrile (eq 17).15

Diketones can also be oxidatively cleaved to dicarboxylic acids, as in the oxidation of phenanthrenequinone to 2,2-biphenyldicarboxylic acid in high yield (eq 18).16

Oxidative Coupling of Ethynyl Compounds.

Under Glaser conditions, ethynyl compounds dissolved in polar, protic solvents are oxidatively coupled by oxygen (or air) in the presence of a catalytic mixture of copper(I) chloride and ammonium chloride in water (eq 19).17a This coupling reaction has been applied to ethynyl-bearing carbinols,18 aliphatic17b and aromatic hydrocarbons,17c thiophenes,17d esters,17e acids,17f ethers,17g nitriles,17h enynes,17i alleneynes,17j a-diynes,17k triynes,17l and tetraynes.17m

Under Hay conditions, tertiary amines complexed with copper(I) chloride are effective catalysts in the oxidative polymerization of 2,6-disubstituted phenols with molecular oxygen to produce high molecular weight polyarylene ethers (eq 20). Tertiary amines such as N,N,N,N-Tetramethylethylenediamine (TMEDA) are preferred due to their ability to solubilize copper salts in nonpolar solvents such as benzene.18

Even though Glaser conditions are applicable to a wide range of substrates, limitations exist when comparisons to Hay conditions are made. For example, unsymmetrical coupling19b and oxidative cleavage of heterocyclic alkynes20 will work under Hay conditions, but not under Glaser conditions. Yet, symmetrical coupling19a is possible under both conditions.1

Oxidative Coupling of Activated Methine Compounds.

In the presence of copper(I) chloride in TMEDA, there occurs oxidative carbon-carbon coupling of compounds containing activated CH, CH2, or CH3 groups that can complex with the copper catalyst. An example is the oxidation of methyl p-tolylcyanoacetate to 1,2-bis(methoxycarbonyl)-1,2-dicyano-1,2-di-p-tolylethane (eq 21).21

Oxidative Dealkylation.

4-Substituted N,N-dimethylanilines undergo oxidative dealkylation in the presence of the catalyst copper(I) chloride and acetic anhydride under an oxygen atmosphere to give the corresponding N-methylacetanilides and N-methylformanilides (eq 22).22

Ullmann Reaction.

Haloanthraquinones undergo Ullmann condensation reactions in the presence of amines in aprotic solvents under an oxygen atmosphere to form other derivatives (eq 23). In this particular reaction, chloromethoxycopper(II) (prepared in situ from the partial oxidation of copper(I) chloride with oxygen in methanol (eq 24)) increases the rate of reaction by increasing the catalytic activity of copper(I) chloride.23

Related Reagents.

Copper(I) Chloride; Palladium(II) Chloride-Copper(I) Chloride.


1. Mijs, W.; de Jonge, C. Organic Synthesis by Oxidation with Metal Compounds; Plenum: New York, 1986; p 423.
2. Kametani, T.; Satoh, Y.; Takemura, M.; Ohta, Y.; Ihara, M.; Fukumoto, K. H 1976, 5, 175.
3. Jallabert, C.; Riviere, H. TL 1977, 1215.
4. Semmelhack, M.; Schmid, C.; Cortés, D.; Chou, C. JACS 1984, 106, 3374.
5. Sparfel, D.; Baranne-Lafont, J.; Nguyen, K.; Capdevielle, P.; Maumy, M. T 1990, 46, 793.
6. (a) Hay, A. JOC 1969, 34, 1160. (b) Hay, A.; Blanchard, H.; Endres, G.; Eustance, J. JACS 1959, 81, 6335. (c) Brackman, W.; Havinga, E. RTC 1955, 74, 937.
7. Karpov, V.; Khidekel, M. JOU 1967, 3, 1625.
8. (a) de Jonge, C.; Hageman, H.; Huysmans, W.; Mijs, W. JCS(P2) 1973, 1276. (b) de Jonge, C. R. H. I.; Hageman, H. J.; Hoentjen, G.; Mijs, W. J. OS 1977, 57, 78; OSC 1988, 6, 412.
9. Kametani, T.; Takahashi, K.; Ohsawa, T.; Ihara, M. S 1977, 245.
10. Capdevielle, P.; Lavigne, A.; Maumy, M. S 1989, 453.
11. Tsuji, J.; Shimizu, I.; Yamamoto, K. TL 1976, 2975.
12. Willershausen, H.; Graf, H. CZ 1991, 115, 356.
13. Tsuji, J.; Takayanagi, H. T 1978, 34, 641.
14. Tsuji, J.; Takahashi, H.; Kajimoto, T. TL 1973, 4573.
15. Kajimoto, T.; Takahashi, H.; Tsuji, J. JOC 1976, 41, 1389.
16. Balogh-Hergovich, É.; Speier, G.; Tyeklar, Z. S 1982, 731.
17. (a) Glaser, C. CB 1869, 2, 422. (b) Bohlmann, F. CB 1953, 86, 657. (c) Zal'kind, Yu. S.; Fundyler, B. M. JGU 1939, 9, 1725. (d) Vaitiekunas, A.; Nord, F. JACS 1954, 76, 2733. (e) Chicoisine, A.; Duport, G.; Dulou, R. BSF 1957, 1232. (f) Schjånberg, E. CB 1938, 71, 569. (g) Arens, J.; Volger, H.; Doornbos, T.; Bonnema, J.; Greidanus, J.; van den Hende, J. RTC 1956, 75, 1459. (h) Bohlmann, F.; Inhoffen, E.; Politt, J. LA 1957, 604, 207. (i) Akhtar, M.; Richards, T. A.; Weedon, B. C. L. JCS 1959, 933. (j) Jones, E.; Lee, H.; Whiting, M. JCS 1960, 341. (k) Armitage, J.; Jones, E.; Whiting, M. JCS 1952, 2014. (l) Cook, C.; Jones, E.; Whiting, M. JCS 1952, 2883. (m) Armitage, J.; Entwhistle, N.; Jones, E.; Whiting, M. JCS 1954, 147.
18. Hay, A. JOC 1962, 27, 3320.
19. (a) Riley, J. JCS 1953, 2193. (b) Jacobs, P.; Davis, M. JOC 1979, 44, 178.
20. Fritsche, U.; Hunig, S. TL 1972, 4831.
21. de Jongh, H.; de Jonge, C.; Mijs, W. JOC 1971, 36, 3160.
22. Murata, S.; Suzuki, K.; Tamatani, A.; Muira, M.; Nomura, M. JCS(P1) 1992, 1387.
23. Arai, S.; Hashimoto, Y.; Takayama, N.; Yamagishi, T.; Hida, M. BCJ 1983, 56, 238.

Edward J. Parish & Stephen A. Kizito

Auburn University, AL, USA



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