Patent ID: 6489513
Filing Date: 2002-12-03
Classification: C07F

Abstract:
A process for the preparation of enantiomerically pure bis-diphenylphosphine oxides of the formula (I) in whichR1 is phenyl, naphthyl, heteroaryl having 4 or 5 carbon atoms and 1 or 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, or cyclohexyl, wherein each R1 is optionally substituted by Râ€², ORâ€², NO2, NH2, NHRâ€², or NRâ€²2, in which each Râ€² is C1-C6-alkyl, R2 is C1-C4-alkoxy, R3 is hydrogen, fluorine, chlorine, or bromine, and R4 and R5, independently of one another, are hydrogen, fluorine, chlorine, bromine, C1-C6-alkyl, or C1-C6-alkoxy, comprising(1) in a first stage, selectively monometalating a bromine compound of the formula â€ƒin which R2 to R5 have the meanings given for formula (I), in a solvent comprising a mixture of tetrahydrofuran and an aromatic hydrocarbon and reacting the resultant metalated compound with a diphenylphosphinic chloride of the formula (II) â€ƒin which R1 has the meaning given for formula (I), which is added without solvent to the metalated compound, to give a diphenylphosphine oxide of the formula (III) â€ƒin which R1 to R5 have the meanings given in formula (I), which is isolated from a solution in an aromatic hydrocarbon by adding a saturated aliphatic hydrocarbon, (2) in a second stage, metalating the diphenylphosphine oxide of the formula (III) in the 6-position and reacting the resultant metalated compound with iodine at a temperature of not less than âˆ’25Â° C., wherein the metalated diphenylphosphine oxide of the formula (III) and iodine are metered in simultaneously such that a small amount of iodine is always present in excess, to give a 2-iodo-diphenyl-phosphine oxide of the formula (IV) â€ƒin which R1 to R5 have the meanings given for formula (I), which is separated off in dissolved form in an aromatic hydrocarbon, (3) in a third stage, converting the 2-iodo-diphenylphosphine oxide of the formula (IV) with copper in an aromatic hydrocarbon solvent into a racemic bis-diphenylphosphine oxide of the formula (I), which is crystallized from a solution in an aromatic hydrocarbon, and (4) in a fourth stage, separating the racemic bis-diphenylphosphine oxide of the formula (I) into its enantiomers by crystallization with an enantiomerically pure mono- or dicarboxylic acid, wherein a first enantiomer is obtained by crystallization from a solution in an aromatic hydrocarbon and a second enantiomer is obtained by hydrolysis and subsequent crystallization from a solution in an aromatic hydrocarbon.