Alkyl Bromides from Alkyl Chlorides using CaBr2/PTC

by Minda Yonovich-Weiss and Yoel Sasson
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Synthesis 34-35 (1984)

Halogen exchange reactions between alkyl halides and metal salts (Finkelstein reaction)[1,2,3] have found only limited synthetic applications in the few examples where the equilibrium could be shifted in the desired direction. In other cases, large excess of the metal halide are required making the procedure uneconomical [4,5].

A new approach to the Finkelstein reaction was recently introduced independently by several groups [6-9] who utilized phase transfer catalysts to accelerate halogen exchange between metal salts in aqueous solutions and alkyl halides in organic phase. It was shown that chloride, bromide, and iodide as their sodium or potassium salts can be efficiently exchanged with various alkyl chlorides or bromides. These reactions still suffer from the disadvantage of being reversible, thus demanding large excess of the donor halide salt (5 - 10 mol ratio) for obtaining significant yields of the alkyl halide product. Alternatively, the aqueous salt of the metal salt was exchanged several times with fresh solutions until the required conversion was obtained.

We have now observed that calcium bromide can serve as a very effective brominating agent for primary alkyl halides in the presence of lipophilic quanternary as phase transfer catalysts according to the following general scheme.

2 R-Cl (org) + CaBr2 ----> 2 R-Br (org) + CaCl2

The reactions were typically carried out at 110oC in the presence of 2 mol% of tetrahexylammonium bromide and in the absence of any additional solvent (Table). Quanternary ammonium or phosphonium salts with less than 25 carbon atoms proved to be non-effective in the catalysis.

Halogen Exchange Reactions between Alkyl Chlorides and CaBr2 Catalyzed by Tetrahexylammonium Bromide[a]

Substrate Products Conversion
b.p at Atmospheric
b.p Reference[10]
C6H5CH2--Cl C6H5CH2--Br 94.8 94 199-201° 201°
n-C4H9--Cl n-C4H9--Br 92.0 89 100-102° 101.6°
n-C6H13--Cl n-C6H13--Br 93.2 92 152.5-155° 155.3°
n-C8H17--Cl n-C8H17--Br 92.8 89 198-201° 200.8°
Cl--CH2--Cl Cl--CH2--Br 32.7 30 67-68.5° 68.1°
Br--CH2--Br 63.1 62 96.0-97.0° 97°
Cl--CH2CH2--Cl Cl--CH2CH2--Br 39.2 38 104-106.5° 107°
Br--CH2CH2--Br 55.4 53 130-131° 131.3°

[a] Amounts Used: R--Cl (0.05 mol); 95% CaBr2 (0.025 mol); (C6H13)4NBr (0.001 mol); reaction temperature: 110°C [b] The conversions were determined by G.L.C (conditions: 20% Carbowax 20 M on Chromosorb W at 100-160°C, 6 ft. column). Products identified by comparison with authentic samples.
[c] Yield of isolated product greater than or equal to 98% purity as determined by G.L.C.

Surprisingly, it was found that the exchange reaction of calcium bromide with primary alkyl bromides is practically non-reversible, provided that the amount of water in the system is limited to 5% w/w of the calcium bromide. Under such conditions, no molar excess of the bromide salt is necessary to achieve 90-95% conversions. When larger amounts of water were present in the system, the conversions were lower. This phenomenon was found to be unique to calcium bromide as a brominating agent and was not observed with sodium and potassium bromides, where the quantity of water in the system had only a minor effect on the conversions. Highly concentrated (95% w/w) solutions of sodium bromide and potassium bromide yielded only 78 and 34% conversions, respectively, when reacted with stoichiometric quantities of n-octyl chloride.

The unique behavior of calcium bromide in these systems is attributed to the very high ratio of activity coefficients of calcium bromide to calcium chloride in highly concentrated aqueous solutions and to the fact that calcium chloride is precipitated from concentrated solutions of calcium bromide. The physical properties of these systems will be published separately.

1-Bromooctane; Typical Procedure;

In a 100 ml round bottomed flask, 1-chlorooctane (14.87 g, 0.1 mol), 95% calcium bromide (10.53 g, 0.05 mol) and tetrahexylammonium bromide (0.8692 g 0.002 mol) The mixture is stirred with a mechanical stirrer for 24 h at 110°C. After this time, G.L.C. analysis (20% Carbowax 20 M on Chromosorb W) shows a 92.8% conversion to 1-bromooctane. The mixture is diluted with dichloromethane (25 ml), the organic layer is separated, washed with water (2 x 25 ml), dried with sodium sulfate, and distilled to give 1-bromooctane of purity 99%; yield: 17.2 g (89%); nd20 : 1.4518 (Ref.10 nd20: 1.4524


[1] R.T. Dillon, J. Am. Chem. Soc. 54, 952 (1932)
[2] H. A. C. McKay, Nature (London) 139, 283 (1937)
[3] H. A. Finkelstein, Br. Dtsh. Chem. Ges. 43 1528 (1910)
[4] W. J. Bailey, E. Fukiwara, J. Am. Chem. Soc. 77 165 (1965)
[5] E. D. Hughes, C. K. Ingols, J. D. H. Mackey J. Chem. Soc. 1955, 3173
[6] Starks and Liotta, Phase Transfer Catalysts. Principles and Applications, Academic Press, New York 1978, p. 117.
[7] M. A. Johnson, R. Yang, U.S. Patent 3641172 (1972). Continental Oil Company: CA 76 99072 (1972).
[8] A. Brändström, H. Kolind-Andersen, Acta Chem. Scand. [B] 29, 201 (1975).
[9] D. Landini, F. Montanari, F. M. Pirisi J. Chem. Soc. Chem Commun. 1974, 879.
[10] Handbook of Chemistry and Physics. 63 Edn. CRC Press Inc., Boca Raton, Florida 1982-1983.