Process for producing 2-bromocyclopentanone

Details Process for producing 2-bromocyclopentanone Process for producing 2-bromocyclopentanone

2003-11-04

2004-09-07

Owens, Amelia A. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

C358S302000, C358S302000

Reexamination Certificate

active

06787673

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a process for producing 2-bromocyclopentanone, which is a useful intermediate for the production of pharmaceuticals.
BACKGROUND OF THE INVENTION
It is disclosed in the Experimental section of Indian J.Heterocycl.Chem., 1991, 1 (3) 117 that a reaction of bromine with cyclopentanone in chloroform gave 2-bromocyclopetanone in a yield of 36%. J. Amer. Chem. Soc., 1985, 107 (25), 7524 discloses a bromination reaction of cyclopetanone using N-bromosuccinimide as a brominating agent, and Synthesis 1981, (12) 987 discloses, as a brominating agent, a bromine complex with an imidazo [1,2-b] pyrldadine derivative. Zh.Obshch.Khim., 1975, 45(9),2100 and Chem.Pharm.Bull., 1973, 21(1), 54 disclose bromination reactions of cyclopentanone enol or enamine with bromine respectively. Since the yield of the first process is not satisfactory and the latter processes required expensive brominating agent and derivatization steps to produce cyclopentanone enol or enamines from cyclopentanone, they are not always satisfactory for an industrial scale of production.
DETAILED DESCRIPTION OF THE INVENTION
According to the present invention, 2-bromocyclopentanone can be advantageously produced in an industrial scale of production.
The present invention provides a process for producing 2-bromocyclopentanone which comprises reacting cyclopetanone with bromine in a biphasic mixture of (i) water and (ii) an organic solvent or mixtures thereof.
2-Bromocyclopentanone is produced, for example, typically by dropwise-addition of bromine to a mixture of a biphasic mixture of water and the organic solvent, and cyclopentanone.
Cyclopentanone is usually used in such an amount that the molar ratios of cyclopentanone to bromine are 20:1 to 1:1, and preferably 10:1 to 1:1, and more preferably 5:1 to 2:1. The amount of water in the biphasic mixture is usually 0.1 to 100 parts by weight, preferably 0.5 to 20 parts by weight per one part by weight of bromine.
Examples of the organic solvent, as the component of the biphasic mixture comprising (i) water and (ii) an organic solvent or mixtures thereof, is typically a water immiscible organic solvent. The water immiscible organic solvent means an organic solvent that can form a biphasic mixture with water.
Specific examples of the organic solvent include, for example, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, 1-chlorobutane, or chlorobenzene;
ethers such as diethyl ether, a diisopropyl ether, tert-butyl methyl ether or the like;
aromatic hydrocarbons such as toluene, benzene, xylene or the like;
aliphatic hydrocarbons such as hexane, heptane or the like;
alcohols such as n-octanol, n-nonyl alcohol, n-decyl alcohol or the like;
esters such as ethyl acetate, butyl acetate, a methyl propionate or the like; and
ketones such as methyl ethyl ketone, methyl isobutyl ketone, or the like. Preferred organic solvent that can form two phases with water is a water immiscible organic solvent that has no carbonyl group. More preferred are halogenated hydrocarbons, and still more preferred is 1-chlorobutane. The amount the organic solvent or mixtures thereof is usually in a range of from 0.1 to 100 parts by weight, preferably 0.5 to 20 parts by weight per one part by weight of bromine.
The addition of bromine is usually conducted at a range of from −10 to 80° C., preferably about 0 to 50° C. After completion of addition of bromine, the temperature is usually maintained thereafter. For example, after completion of the addition of bromine, the temperature is usually maintained for about 0.5 to 100 hours, preferably for 2 to 50 hours. The temperature after completion of the addition of bromine is usually maintained in the range of from −10 to 80° C., preferably about 0 to 50° C. 2-Bromocyclopentanone thus produced can be isolated by conventional methods. 2-Bromocyclopentanone can be isolated, for example, by separating oil phase and a water phase and evaporating the solvent of the oil phase containing 2-bromocyclopentanone. Unreacted cyclopetanone, if any, may be separated from 2-bromocyclopentanone by distillation. The recovered cyclopentanone can be reused in the present reaction. 2-Cyclopentanone thus obtained may be further purified by distillation, column chromatography or the like.
2-Bromocyclopentanone is, for example, suitably used to produce 2-cyclopentene-1-one by reacting 2-bromocyclopentanone with abase (dehydrobromonation reaction). Typical examples of the base include lithium carbonate, which is usually used in the co-presence of lithium bromide. Further specific conditions of the dehydrobromination reaction are referred to, for example, JP2000178220A. Thus produced 2-cyclopentene-1-one may be purified, if necessary, by distillation, column chromatography and/or the like.
According to the present invention, 2-bromocyclopentanone can be produced from cyclopentanone and bromine with good selectivity.


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