GB2226315A - Organometallic 2-fluoro-5-bromophenyl compound - Google Patents

Abstract

A compound of formula IV, useful as an intermediate in the production of pesticides <IMAGE> in which formula IV, M represents a metallic moiety in particular Mg Br or Li. Such a compound is useful as an intermediate in the preparation of compounds claimed in GB 8927841.0 and GB 8705940.8 (GB 2187731A) <IMAGE>

Description

INTERMEDIATES USEFUL IN THE PRODUCTION OF PESTICIDES This invention relates to production of intermediates useful in the manufacture of pesticides.

In International Patent Application No. CB 85/00146 there are disclosed methods for the preparation of compounds of formula I I: RACH3=CR4CHDRB in which formula: RA represents a group ArCRlR2 - in which Ar represents a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, C1-C6 alkyl or haloalkyl groups; R1 and R2 together with the carbon to which they are attached represent a C3-C6 cycloalkyl group optionally substituted by one or more halogen atoms or C1-C6 alkyl groups.

R3 and R4 which may be identical or differ, represent hydrogen, haloyen or C1 -C6 alkyl groups and RB represents the residue of an alcohol RB CHDOH in which D is hydrogen or cyano and of which the EMIR, ) 2,2-dimethyl-3-(2,2-dibromovinyl) cyclopropane carboxylic ester is 'significantly insecticidal, the configuration of RA and CHDRB about the double bond being mutually trans.

Compounds I in which RB represents 4-fluoro-3-phenoxyphenyl are of particular interest and may be prepared inter alia by reaction of the Grignard reagent, 4-fluoro-3-phenoxyphenyl magnesium bromide with a suitable substrate. The bromide required for preparation of this Grignard reagent (5-bromo-2-fluorodiphenyl either) (II), has, however, been available hitherto only with difficulty.

It has now however been found that the bromide and other Brmediates can be generated in good yield from 2,4-dibromoprobenzene, which is available commercially although generally aminated with the isomer 3,4-dibromofluorobenzene.

In UK Patent Application No. 8705940 of which the present ication is a [)lvlsional Application there is described a ess for the production of a boronic acid of formula III,

ertible into 5-bromo-2-fluorodiphenyl ether (II), in which an nometallic of formula IV, obtainable from 2,4-dibromofluoroene,

zilch formula IV M represents a metallic moiety such as -MgX, zing a halogen) t an alkali metal such as lithium is treated a trialkoxy borne of formula B(OR)3, R representing an group (e.g. a C1-C6 alkyl group which is preferably methyl) he product is hydrolysed.

he present invention comprises a compound of formula IV oer has been fod that the boronic acid III crystallizes y and that bhe crystals are substantially free of impurities and particularly isomers of the acid III derived from metallation at the 4-bromo position of 2,4-dibromofluorobenzene or derived from 3,4-dibromofluorobenzene impurity in the starting material.

Preferably, therefore the boronic acid III is crystallised and the crystals are isolated prior to further treatment.

The amount of the metal or metal alkyl used to treat 2,4-dibromofluorobenzene and thus produce the organometallle IV may be reduced to 80% or less of the stoichiometric amount.

Under these conditions bromine at the 2-position in 2,4-dibromofluorobenzene may react in preference to bromine at the 4-position and 2,4-dibromofluorobenzene may react in preference to 3,4-dibromofluorobenzene present as a contaminant, so that a good yield of the desired isomer of formula IV is obtained. Amounts less than 60% of stoichiometric are undesirable as the yield Is unnecessarily decreased.

The boronic acid III may be converted Into the Intermediate 5-bromo---;luorodiphenyl ether II, by oxidation, suitably using hydrogen peroxide, to the corresponding phenol V the corresponding C1-C6 alkoxide of which VI reacts with a halobenzene, in' which the halogen is chlorine, bromine or iodine, under Ullmann conditions e.g. in the presence of a copper catalyst such as copper bronze or a CuI or CuII halide to give II

The Invention is illustrated by the following Example:: Di hvdroxv-(5-bromo-2-fluoroqhenvl )-borane A solution of 2,4-dibromofluorobenzene (12.79, containing 30% 3,4-dibromofluorobenzene) in dry tetrahydrofuran (THF) (lOml) is added over 5 min to a stirred suspension of magnesium turnings (l.l5g) in dry THF (50ml) under an atmosphere of nitrogen and cooled in a water bath. After 1 hour, when all the magnesium has reacted, this reagent is added over 20 min to a stirred solution of trimethoxyborane (7ml) in dry diethyl ether (80ml) under an atmosphere of nitrogen and cooled at 78"C for a further 15 min.

and glacial acetic acid (6ml) added followed by water (50ml).

The mixture Is warmed to room temperature, extracted with diethyl ether (x3), washed with water, dried and the solvent evaporated under reduced pressure. The residue Is stirred with carbon tetrachloride (30ml) > and then cooled at 0 C. The crystals of dihydroxy-(5-bromo-2-fluorophenyl)-borane are filtered off and washed with a little carbon tetrachloride. Yield 2.89 m.pt.

173-174"C. s 5-Bromo-2-flvoroDhenol To a stirred solution of dihydroxy-(5-bromo-2-fluorophenyl)- borane (2g) in diethyl ether (lOml) is added chloroform (lOml) and 30% hydrogen peroxide (lOml), The mixture is stirred for 18 hours at room temperature, diluted with water, extracted with diethyl ether (x3) and back extracted with 2M NaOH (or, in an alternative embodiment producing relatively increased yields, with stronger sodium hydroxide, e.g. 5M NaOH). The aqueous layer is acidified with aqueous 2N HCI extracted with diethyl ether (x3), dried and the solvent evaporated to give S-bromo-2-fluorophenol, yield 1.25g.A sample is purified by t.l.c. on silica gel eluted with 30% diethyl ether in petroleum ether b.p. 60-80"C nDl.5564. Alternatively, the product is distilled b.p. 52-54 /0.2 mm Hg.

S-Bromo-2-fluoro-diqhenvl ether Sodium hydride (0.2g of 60% dispersion in oil) is added in small portions to a stirred solution of 5-bromo-2-fluorophenoi (lug) in 2-methoxyethyl ether (lml) under nitrogen and cooled in a water bath. Cuprous bromide (0.099 ) and a solution of bromobenzene (1.5ml) in 2-methoxymethyl ether (2ml) were added and the mixture refluxed for 6 hours. The mixture was poured onto water, extracted with petroleum ether b.p. 60-80 (x3), washed with water, dried, solvent evaporated and the residue distilled at 0.02 mm Hg b.pt. 80-82 C nD 1.5708, Yield 0.55g.

Claims (4)

1. A compound of formula IV,

in which formula IV, M represents a metallic moiety.

2. A compound according to Claim 1, in which M represents -MgX wherein X is a halogen.

3. A compound according to Claim 1, in which M represents an alkali metal.

4. A compound according to Claim 3, in which M represents lithium.