Pentamethylene bromide

Pentamethylene bromide has been prepared by the action of fuming hydrobromic acid on pentamethylene glycol,2 or 1,5-diphenoxypentane 3 by the action of hydrobromic acid on an acetic acid solution of 1,5-di-isoamyloxypentane 4 and by the action of phosphorus pentabromide on benzoyl piperidine.5 

A hydrobromic acid solution (Org. Syn. Coll. Vol. 1, 1941, 26) is prepared in a 500-cc. round-bottomed flask by passing sulfur dioxide into a mixture of 120 g. (37.7 cc., 0.75 mole) of bromine, 50 cc. of water, and 150 g. of crushed ice. This is equivalent to a mixture of 253 g. (1.5 moles) of 48 per cent hydrobromic acid and 74 g. of concentrated sulfuric acid. To the mixture 21.5 g. (0.25 mole) of tetrahydropyrane (p. 90) is added, a reflux condenser is attached to the flask, and the light brown homogeneous mixture is refluxed for three hours (Note 1). 

The heavy lower layer is separated (Note 2), washed once with a saturated solution of sodium bicarbonate, once with water, and then dried over 4-5 g. of anhydrous calcium chloride. The crude product is decanted from the calcium chloride, and the drying agent is rinsed once or twice with a small quantity of ethyl bromide which is added to the main product. The mixture is distilled under reduced pressure, and the pentamethylene bromide, 

The submitter refluxed the mixture for ten hours, but the checkers obtained equally good yields in three hours. 

The upper aqueous layer contains considerable unchanged hydrobromic acid. If this layer is distilled, about 150 g. (0.9 mole) of constant-boiling hydrobromic acid (b.p. 123-124°/748 mm.) may be recovered. 

The methods of preparing pentamethylene bromide are given in Org. Syn. Coll. Vol. 1, 1941, 428, where the preparation of the dihalide from benzoylpiperidine and phosphorus pentabromide is described in detail. The procedure given above is based upon the work of Paul.1 

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Pentandiol has been prepared by the reduction of methyl glutarate. and by the reduction of epoxy-1,5-peiitanol-5. It has also been prepared from pentamethylene bromide by conversion to the cliacetate followed by hydrolysis to the glycol. The procedure described is a modification of that of Connor and Adkins. ... 

Pentamethylene bromide prepared by this method has been reported to contain a considerable amount of benzonitrile, and a procedure is given for removing it. 

If piperidine is available, benzoyl piperidine for use in the preparation of pentamethylene bromide (p. 70) may be prepared by direct benzoylation. A mixture of 105 g. of sodium hydroxide (2.6 moles), 170 g. of piperidine (2.0 moles) (b. p. 104-1080) and 800 cc. of water are treated with 280 g. (2 moles) of benzoyl chloride using the apparatus and procedure described above the temperature is kept at 35-40°. The oily product is separated after dilution with 250 cc. of benzene if necessary (Note 5), dried with a small quantity of potassium carbonate and distilled. The portion boiling at 172-1740/12 mm. weighs 330-345 g. (87-91 per cent of the theoretical amount). The first few... 

It has been suggested in the literature1 that the ben-zonitrile may be removed from the pentamethylene bromide by shaking repeatedly with concentrated sulfuric acid. This did not prove satisfactory in the laboratory on account of the formation of emulsions. When a solvent such as petroleum ether is added, the emulsions may be avoided but the yield of final product is always lower than that obtained by the method described. 

Pentamethylene Bromide (Coll. Vol. i, 419) Tetrahydrofurfuryl alcohol passed over alumina at 370-380 gives 1,2-dihydropyran in 44 per cent yield. Hydrogenation in the presence of platinum produces pentamethylene oxide (1,5-epoxypentane), which is converted to the bromide by heating with hydrogen bromide in glacial acetic acid. Ibe yield is 65 per cent, based upon r,2-dihydropy-ran. Paul, Bull. soc. chim. [4] 53, 1489 (1933). 

The amine group in primary amines can be replaced by halogen by warming the benzoyl derivative with phosphorus pentachloride or phosphorus pentabromide. Oftentimes, the separation of the halide from the benzonitrile, which is also formed, is troublesome. The process has been applied mostly to high-moIecuIar-weight amines obtained by the Hofmann degradation of acid amides or by reduction of nitriles." Diamines lead to dihalogen derivatives." If N-benzoyl piperidines are treated, substituted pentamethylene halides are formed. An example is the synthesis of pentamethylene bromide by the action of phosphorus pentabromide on N-benzoyl piperidine (72%). ... 

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