GB2187731A

GB2187731A - Process for the production of dihydroxy-(5-bromo-2-fluorophenyl)-borane

Info

Publication number: GB2187731A
Application number: GB08705940A
Authority: GB
Inventors: Michael Elliott; Norman Frank Janes; Bhupinder Pall Singh Khambay
Original assignee: National Research Development Corp UK
Current assignee: National Research Development Corp UK
Priority date: 1986-03-13
Filing date: 1987-03-13
Publication date: 1987-09-16
Anticipated expiration: 2007-03-13
Also published as: EP0238272A2; JPH08310987A; DE3778947D1; JPH08310988A; JP2618220B2; JPS62252740A; GB2187731B; US5068403A; EP0238272A3; GB2226312A; EP0238272B1; JP2618221B2; GB8705940D0; JP2579310B2; GB8927841D0

Description

1 GB 2 187 731 A 1

SPECIFICATION

Intermediates useful in the production of pesticides This invention relates to production of intermediates usef ul in the manufacture of pesticides. 5 In International Patent Appi ication No. G B 85/00146 there are disclosed methods for the preparation of compounds of formula 1 1: RACR3=CR4CHID13B 10 in which formula:

RA represents a group ArCR, R2 - in which Ar represents a phenyl or naphthyl group optionally substituted by one or more halogen, alkoxy, haloalkoxy, methylenedioxy, Cl-C6 alkyl or haloalkyl groups; R, and R2 together with the carbon to which they are attached represent a C3-C6 cycioalkyl group optionally substituted by one or more halogen atoms or Cl-C6 alkyl groups. 15 R3 and R4 which may be identical or differ, represent hydrogen, halogen or Cl-C6 alkyl groups and RB represents the residue of an alcohol RB CHDOH in which D is hydrogen or cyano and of which the [IR, cis] 2,2-dimethyi-3-(2,2-dibromovinyi) cyclopropane carboxylic ester is significantly insecticidal, the configuration of RA and CHDRB about the double bond being mutually trans.

Compounds 1 in which R13 represents 4-fluoro-3-phenoxyphenyl are of particular interest and may be 20 prepared interalia 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-brom o-241 uorodi phenyl ether) (11), has, however, been available hitherto only with difficulty.

r 25 1 r 30 C0 It has now however been found thatthe bromide and other intermediates can be generated in good yield from 2,4-dibromofluorobenzene, which is available commercially although generally contaminated with the 35 isomer 3,4-dibromofluorobenzene.

Accordingly, the present invention comprises a process forthe production of a boronic acid of formula Ill, 40 45 convertible into 5-bromo-2-fluorodiphenyl ether (11), in which an organometallic of formula IV, obtainable A from 2,4-dibromofluorobenzene, 50 0 55 Q in which formula IV M represents a metallic moiety such as -M9X, (X being a halogen) oran alkali metal such 60 as lithium is treated with a trialkoxy borane of formula B(OR6 R representing an alkyl group (e.g. a Cl-C6 alkyl group which is preferably methyl) and the product is hydrolysed.

It has been found that the boron ic acid 111 crystallizes readily and that the crystals are substantially free of impurities and particularly isomers of the acid Ill derived from metallation at the 4-bromo position of 2,4-dibromofluorobenzene or derived from 3,4-dibromofluorobenzene impurity in the starting material. 65 2 GB 2 187 731 A 2 Accordingly, in a preferred embodiment of the present process, the boronic acid Ill is crystal lised and the crystals are isolated prior to furthertreatment.

The amount of the metal or meta I alkyl used to treat 2,4-di brornofl uo ro benzene and thus produce the organometallicIV maybe reduced to 80% or less of the stoichiometricamount. Under these conditions bromine at the 2-position in 2,4-dibromofluorobenzene may react in preference to bromine at the 4-position 5 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 W is obtained. Amounts less than 60% of stoichiometric are undesirable as the yield is unnecessarily decreased.

The boronic acid 111 maybe converted into the intermediate 5-bromo-241 u orod i phenyl ether Il, by oxidation, suitably using hydrogen peroxide, to the corresponding phenol V the corresponding Cl-C6 10 alkoxide of which V] reacts with a halobenzene, in which the halogen is chlorine, bromine or iodine, under W mann conditions e.g. in the presence of a copper catalyst such as copper bronze or a Cul or Cull halide to give 11 15 20 The present invention includes in a further aspect an organometallic of formula IV,a boronicacid Ill,a phenol V, a phenoxide V] and processes as hereinbefore described for the conversion of 25 2,4-dibromofluorobenzeneto the organometallic IV, of the boronic acid Ill to the phenol V, of the phenol Vto the phenoxideV1 and of the phenoxideVI to the intermediate 5-bromo-2fluorodiphenyl ether.

The invention is illustrated by the following Example:

Dihydroxy(5-bromo-2fluorophenyl)-borane 30 A solution of 2,4-dibromofi uorobenzene (1 2.7g, containing 30% 3,4- dibromofluorobenzene) in dry tetrahydrofu ran (THF) (1 Orni) is added over 5 min to a stirred suspension of magnesium turnings (1. 1 5g) in dry THF (50mi) 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 (7mi) in dry diethyl ether (80mi) under an atmosphere of nitrogen and cooled at - 78'C. The mixture is stirred at-780C 35 fora further 15 min. and glacial acetic acid (6m]) added followed by water (50mi). 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 (30mi) and then cooled at WC. The crystals of dihydroxy-(5-bromo-2-fluorophenyi)-borane are filtered off and washed with a little carbon tetrachloride. Yield 2.8g m.pt. 173-174C. 40 5-Bromo-2-fluorophenol To a stirred solution of dihydroxy-(5-bromo-2-fluorophenyi)-borane (2g) in diethyl ether (10mi) is added chloroform (1 Orni) and 30% hydrogen peroxide (10mi). 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 45 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 5-bromo-2-fluorophenol, yield.1.25g. A sample is purified byt.l.c. on silica gel eluted with 30% diethyl ether in petroleum ether b.p. 60-80'C n[D1.5564. Alternatively, the product is distilled b.p. 52-54010.2 mm Hg. 50 5-Bromo-2-fluoro-diphenyl ether Sodium hydride (0.2g of 60% dispersion in oil) is added in small portionsto a stirred solution of 5-bromo-2-fluorophenol (1 g) in 2-methoxyethyl ether (1 mi) under nitrogen and cooled in a water bath.

Cuprous bromide (0.09g) and a solution of bromobenzene (1.5m[) in 2methoxymethyl ether (2m]) were 55 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 atO.02 mm Hg b.pt. 80-820C nD 1.5708, Yield 0.55g.

Claims

CLAIMS 60

1. A process forthe production of a boronic acid of formula Ill, 3 GB

2 187 731 A 3 Sr M e) (o 5 in which an organometallic of formula W, 10 iv 15 in which formula IV, M represents a metallic moietysuch as -MgX, X being a halogen or an alkali metal is treated with a trialkoxy borane of formula B(CR6 R representing an alkyl group andthe product hydrolysed. 20 2. A process according to Claim 1, in which M in the compound of formula IV represents -M9Br.

3. A process according to Claim 1, in which M in the compound of formula 11 represents an alkali metal which is lithium.

4. A process according to any preceding Claim, in which R in the compound of Claim 1 represents a Cl-C6 alkyl group. 25

5. A process according to any preceding Claim, in which the boronic acid (111) is crystallised substantially free of any isomers thereof.

6. A process according to any preceding Claim, in which the compound IV is produced by metal lation at the 4-bromo position 2,4-dibromofluorobenzene using metal or metal alkyl in an amount which is no greater than 80% of the stoichiometric amount required. 30

7. A process for the production of 5-bromo-241 uorodiphenyl ether in which a boronic acid 111 produced in accordance with any preceding Claim is oxidised to 5-bromo-2-fluorophenol the Cl-C6 alkoxide of which is reacted with a halobenzene under Ulmann conditions.

8. An organometallic compound of formula IV.

9. A boronic acid of formula Ill. 35

10. 5-bromo-2-fluorophenol

11. An alkali metal phenoxide of 5-bromo-2-fluorophenol.

Printed for Her Majesty's Stationery Office by Croydon Printing Company (U K) Ltd, 7187, D8991685.

Published by The Patent Office, 25 Southampton Buildings, London WC2A 1 AY, from which copies maybe obtained.