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WO1992013820A1 - Procede de preparation d'ethers d'alcoyle-4-halophenyle - Google Patents

Procede de preparation d'ethers d'alcoyle-4-halophenyle Download PDF

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Publication number
WO1992013820A1
WO1992013820A1 PCT/GB1992/000116 GB9200116W WO9213820A1 WO 1992013820 A1 WO1992013820 A1 WO 1992013820A1 GB 9200116 W GB9200116 W GB 9200116W WO 9213820 A1 WO9213820 A1 WO 9213820A1
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Prior art keywords
alkyl
ether
halide
alkylation
reaction
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Ceased
Application number
PCT/GB1992/000116
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English (en)
Inventor
Gareth Andrew Deboos
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Imperial Chemical Industries Ltd
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Imperial Chemical Industries Ltd
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Filing date
Publication date
Application filed by Imperial Chemical Industries Ltd filed Critical Imperial Chemical Industries Ltd
Publication of WO1992013820A1 publication Critical patent/WO1992013820A1/fr
Anticipated expiration legal-status Critical
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/16—Preparation of ethers by reaction of esters of mineral or organic acids with hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
    • C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms

Definitions

  • This invention relates to a novel process for the preparation of alkyl 4-halophenyl ethers, and to products whenever prepared by the said process.
  • Alkyl 4-halophenyl ethers are useful as intermediates for the preparation of certain insecticidally active compounds, for example, those described in UK Patent Application Nos 2178739-A and 2187452-A.
  • Known methods of preparation of alkyl 4-halophenyl ethers from phenol as the basic raw material fall into two categories.
  • phenol is halogenated in the 4-position to give a 4-halophenol which is then isolated and subsequently alkylated.
  • the halogenation step has been carried out using an elemental halogen directly as the halogenating agent or by the use of a halide ion in the presence of an oxidising agent.
  • the 4-halophenol is then isolated by separation or extraction from the reaction medium, and may have to be purified before further processing by reaction with an alkylating agent, usually an alkyl derivative having a displaceable leaving group, such as an alkyl halide or an alkyl sulphate, preferably in the presence of a base.
  • an alkylating agent usually an alkyl derivative having a displaceable leaving group, such as an alkyl halide or an alkyl sulphate, preferably in the presence of a base.
  • the final product must then be isolated from the reaction medium. Examples of these separate reaction steps may be found in Organic Syntheses, Collective Volume 1, pl28 and in Olah, Friedel Crafts and Related Reactions, 1965, Volume 2, Part 1.
  • a particular disadvantage associated with the known two stage methods of preparation of alkyl 4-halophenyl ethers is the generption in one or both stages of unwanted by-products, such as those derived from the leaving group of the alkylating agent (for example an alkylsulphate salt where a dialkylsulphate is used, or a halide salt where an alkyl halide is used) and a halide salt derived from halogenation using an elemental halogen.
  • the alkylating agent for example an alkylsulphate salt where a dialkylsulphate is used, or a halide salt where an alkyl halide is used
  • a halide salt derived from halogenation using an elemental halogen for example an alkylsulphate salt where a dialkylsulphate is used, or a halide salt where an alkyl halide is used
  • the present invention provides a process for the preparation of an alkyl 4-halophenyl ether of formula (I) wherein R is C. , straight or branched chain alkyl and X is bromo or chloro, which comprises the step of alkylation of phenol by reaction with an alkyl halide of formula R-X (II) in the presence of a base, followed by the step of halogenation of the intermediate alkyl phenyl ether obtained thereby, characterised in that the halogenating agent is elemental halogen derived by oxidation of the anionic halide by-product of the alkylation step.
  • the invention provides a process as hereinbefore described, further characterised in that the intermediate alkyl phenyl ether is not isolated prior to the halogenation step.
  • the process of the invention offers improved efficiency over known methods in that the halide anion generated from the alkylating agent in the first step is retained and used as the source of the halogenating agent in the second step.
  • This complete consumption of the alkyl halide reagent represents improved efficiency and reduced material costs over known methods and reduces effluent production significantly by reducing by-products derived from the alkylating and halogenating reagents.
  • the process of the invention does not impose a requirement for complete isolation of the intermediate alkyl phenyl ether.
  • Stoichiometrically equivalent amounts of phenol and a water-soluble base are dissolved in water.
  • Preferred bases are alkali metal hydroxides, especially sodium and potassium hydroxide.
  • a suitable dilution factor is within the range of 2-6 moles of phenol per 1000 cm 3 of water, and preferably 4 moles of phenol per 1000 cm 3 of water.
  • the appropriate alkyl halide alkylating agent is then added to the stirred aqueous phenol salt solution.
  • the alkyl halide is preferably added neat, but may alternatively be added in solution in a water-immiscible, inert organic solvent, such as toluene.
  • the alkylation reaction is satisfactorily achieved using a molar ratio of 1.0-2.0 moles of alkyl halide per mole of phenol, but the advantage of efficient usage of raw materials is best achieved by using a smaller excess of alkylating agent in the range of 1.0-1.5, and preferably 1.0-1.25 moles of alkyl halide per mole of phenol.
  • the alkylation step may be carried out at atmospheric pressure or under externally applied pressure up to 20 atmospheres. In a preferred embodiment the reagents are mixed at atmospheric pressure and sealed and the reaction occurs under autogenous pressure.
  • the reaction temperature may be within the range 35-100°C, the lower end of this range normally being preferred for reactions at or somewhat above atmospheric pressure, and the upper end of the range being preferred when greater pressures are used.
  • Reaction times vary according to the pressure and reagents employed, but are typically of the order of 16 to 24 hours at atmospheric pressure falling to 6 to 12 hours or less under pressure when the alkylating agent is an alkyl bromide. Reaction times when alkyl chlorides are used as alkylating agents may in some cases be considerably longer than those mentioned for alkyl bromides.
  • the alkylation reaction may optionally be catalysed by the addition of a catalytic quantity of a phase transfer catalyst, for example a quaternary ammonium salt such as a tetra-n-butylammonium halide.
  • a phase transfer catalyst for example a quaternary ammonium salt such as a tetra-n-butylammonium halide.
  • the reaction mixture is acidified by the addition of an amount of a mineral acid, preferably sulphuric acid, which is stoichiometrically equivalent to the amount of phenol used in the alkylation step.
  • Acidification reconverts unreacted phenate salt to phenol and generates hydrogen halide from the halide by-product formed during the alkylation reaction.
  • the acidified mixture is allowed to separate into an organic and an aqueous phase.
  • the organic phase contains principally unreacted phenol and the intermediate alkyl phenyl ether.
  • the unreacted phenol is separated from the intermediate product by extraction into an aqueous solution of a base.
  • the aqueous solution of the base is in fact that to be used in a subsequent alkylation reaction according to the invention, thereby providing efficient recycling of unreacted phenol.
  • the halogenation step that the halide anion is present in an amount representing a small excess over the stoichiometric amount calculated on the basis of intermediate alkyl phenyl ether, preferably 1-1.1 molar equivalents and optimally 1.01-1.05 molar equivalents. Incomplete reaction at the alkylation stage and losses during the intermediate separation of the organic and aqueous phases may disturb this optional ratio of reactants, leading to a requirement for adjustment, usually by addition of halide anion, typically in the form of an alkali metal halide.
  • the quantity of crude intermediate alkyl phenyl ether in the organic phase may be assayed by weight and adjusted as necessary on consideration of intermediate purity as determined by standard analytical techniques, such as gas liquid chromatography.
  • the amount of halide anion in the aqueous phase may be assayed by standard techniques, such as titrimetric methods. Adjustment of halide anion content may be achieved, where necessary, by addition of solid alkali metal halide, for example sodium halide.
  • the residual organic phase containing the intermediate alkyl phenyl ether is then recombined with the acidified aqueous phase containing hydrogen halide derived from the alkyl halide alkylating agent and added halide where appropriate.
  • the pH of the aqueous phase is adjusted to pH 0-2 if necessary by the addition of further mineral acid, and an oxidising agent suitable for the generation of elemental halogen from aqueous hydrogen halide solution is added to the stirred reaction mixture in an amount which is stoichiometrically equivalent to the calculated amount of alkyl phenyl ether present in the organic phase.
  • a preferred oxidising agent is hydrogen peroxide.
  • the reaction time may be in the range 2-36 hours depending on the reagents used and the reaction temperature, but will typically be with i n the range of 2-10 hours in the case of bromination reactions. Chlorination reaction times may be considerably longer than those observed for bromination reactions.
  • the reaction mixture On completion of the halogenation reaction, the reaction mixture is allowed to separate into an organic and an aqueous phase.
  • the organic phase is separated and the alkyl 4-halophenyl ether product isolated and purified, if desired, by standard techniques, for example washing of the organic phases to remove traces of water-soluble by-products, distillation of organic solvents, where employed, and distillation of the end product itself.
  • Yields of isolated product are typically of the order of 85% prior to purification, and are equivalent or superior to those obtained by known two-stage methods.
  • the process of the invention also leads to a very high level of selectivity of halogenation, with minimal production of alkyl 2-halophenyl ethers or di- or tri-halogenated derivatives.
  • reaction of phenol with alkyl bromides according to the method of the invention leads to higher yields and improved selectivity over the corresponding reaction with alkyl chlorides, due to the inherently higher reactivity of the former over the latter.
  • reaction steps described herein may be performed substantially as described herein or according to any routine variation thereof. Progress of the reaction steps may be monitored, if desired, by any suitable technique used routinely in the art, for example gas liquid chromatography (GLC). Reaction products may be identified by any of the standard methods of the art. Since the products are widely available, comparison with reference samples using GLC or GLC-Mass spectrometry (GLC-MS) is particularly suitable, as is Nuclear Magnetic Resonance spectrometry (NMR).
  • GLC gas liquid chromatography
  • NMR Nuclear Magnetic Resonance spectrometry
  • EXAMPLE 1 This Example illustrates the preparation of ethyl 4-bromophenyl ether (4-bromophenetole) in which the alkylation step is carried out at atmospheric pressure.
  • the upper (organic) layer containing principally ethyl phenyl ether (0.85 mole determined by weight adjusted for purity on the basis of gas liquid chromatography), was extracted with an aqueous solution of sodium hydroxide (85.lg of 47% NaOH in 250g water) to recover unreacted phenol for recycling as the sodium salt dissolved in the aqueous sodium hydroxide solution component of a subsequent alkylation batch.
  • the lower (aqueous) layer obtained by separation of the reaction mixture of the alkylation step as described in Step 1 above, was treated with activated carbon to remove residual phenol, and the bromide content was adjusted to 1.024 moles per mole of ethyl phenyl ether as necessary by the addition of sodium bromide following assay of the amount of bromide anion present in the aqueous phase using a standard silver nitrate titrimetric method.
  • the aqueous mixture was acidified by the addition of concentrated sulphuric acid (90g of H-SO,, specific gravity 1.84) and the ethyl phenyl ether product from the alkylation step was added.
  • the stirred mixture was warmed to 30°C and hydrogen peroxide (144.7g of 30% aqueous H-0 2 , 1.277 moles) was added gradually over 3 hours; the mixture was then stirred for a further hour, the temperature of the mixture being maintained at 28-32°C throughout the 4 hour period.
  • the mixture was allowed to separate and the organic layer collected and washed with aqueous sodium bisulphite solution (llg of 40% material in 106g water).
  • the reactor vessel was sealed and the agitator activated.
  • the vessel was heated to 91°C and maintained at this temperature (with agitation) for 8 hours.
  • reaction mixture After cooling to the ambient temperature, the reaction mixture was recovered and allowed to separate.
  • sodium hydroxide 85.lg of 47% NaOH in 250g water
  • the product was characterised by comparison of its GLC signal with an authentic sample.
  • This Example illustrates the preparation of n-butyl 4-bromophenyl ether in which the alkylation step is carried out under autogenous pressure in a sealed reactor vessel.
  • a mixture of sodium hydroxide (68.lg of 47% material, 0.8 mole), water (200g), phenol (75.2g, 0.8 mole) and n-butyl bromide (109.6g, 0.8 mole) was charged to a sealable reactor vessel fitted with an agitator for the contents.
  • the reactor vessel was sealed and the agitator activated.
  • the vessel was heated to 93°C and maintained at this temperature (with agitation) for 12 hours.
  • reaction mixture was acidified to pH 1.5 by addition of concentrated sulphuric acid (8.3g, 0.08 mole) and then allowed to separate.
  • the stirred mixture was warmed to 30°C and hydrogen peroxide (99g of 30% aqueous H-0 2> 0.874 moles) was added gradually over 3.25 hours.
  • the mixture was stirred for a few minutes then allowed to separate and the organic layer collected and washed with aqueous sodium bisulphite solution (16g of 40% material in lOOg water).
  • n-butyl bromophenyl ether 131.4g as a straw-coloured liquid.
  • the product was characterised by GLC-MS and the structure of the major component was consistent with n-butyl bromophenyl ether.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

On décrit un procédé de préparation d'un éther d'alcoyle 4-halophényle de formule (I), dans laquelle R représente un alcoyle C1-4 à chaîne droite ou ramifiée et X représente bromo ou chloro, comprenant l'étape d'alcoylation de phénol par réaction avec un halogénure d'alcoyle de formule R-X (II) en présence d'une base, ensuite l'étape d'halogénation de l'éther phénylique d'alcoyle intermédiaire obtenu au moyen de celle-ci, caractérisée en ce que l'agent halogéné est de l'halogène élémentaire dérivé par oxydation du sous-produit de l'halogénure anionique lors de l'étape d'alcoylation. L'invention permet d'obtenir des produits de formule (I) lorsque ceux-ci sont préparés selon le procédé. `
PCT/GB1992/000116 1991-02-06 1992-01-21 Procede de preparation d'ethers d'alcoyle-4-halophenyle Ceased WO1992013820A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9102519A GB9102519D0 (en) 1991-02-06 1991-02-06 Chemical process
GB9102519.7 1991-02-06

Publications (1)

Publication Number Publication Date
WO1992013820A1 true WO1992013820A1 (fr) 1992-08-20

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PCT/GB1992/000116 Ceased WO1992013820A1 (fr) 1991-02-06 1992-01-21 Procede de preparation d'ethers d'alcoyle-4-halophenyle

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GB (1) GB9102519D0 (fr)
WO (1) WO1992013820A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4443592C1 (de) * 1994-12-07 1996-04-25 Great Lakes Chem Konstanz Gmbh Verfahren zur Herstellung von Alkyl-4-bromphenylethern
EP0761633A3 (fr) * 1995-08-26 1997-07-02 Hoechst Ag Procédé pour la préparation d'éthers 4-bromophényl alkyl
FR2772372A1 (fr) * 1997-12-15 1999-06-18 Rhodia Chimie Sa Procede de o-alkylation de composes aromatiques hydroxyles
WO2010015559A1 (fr) * 2008-08-05 2010-02-11 Basf Se Procédé pour la fabrication de dérivés 4-bromophényliques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4517388A (en) * 1982-10-29 1985-05-14 Samuel Braverman Process for the selective preparation of parabromophenol and its derivatives
EP0429975A1 (fr) * 1989-11-27 1991-06-05 Bromine Compounds Ltd. Procédé de préparation de 4,4'-dibromo-diphényl-éther

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4517388A (en) * 1982-10-29 1985-05-14 Samuel Braverman Process for the selective preparation of parabromophenol and its derivatives
EP0429975A1 (fr) * 1989-11-27 1991-06-05 Bromine Compounds Ltd. Procédé de préparation de 4,4'-dibromo-diphényl-éther

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
METHODEN DER ORGANISCHEN CHEMIE (HOUBEN-WEYL) vol. VI/3, 1965, STUTTGART (GEORG THIEME VERLAG) pages 54 - 55; H. MEERWEIN: 'Aether' *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4443592C1 (de) * 1994-12-07 1996-04-25 Great Lakes Chem Konstanz Gmbh Verfahren zur Herstellung von Alkyl-4-bromphenylethern
EP0716069A1 (fr) * 1994-12-07 1996-06-12 Great Lakes Chemical Konstanz GmbH Procédé pour la préparation d'éthers alkyliques 4-bromophényliques
EP0761633A3 (fr) * 1995-08-26 1997-07-02 Hoechst Ag Procédé pour la préparation d'éthers 4-bromophényl alkyl
FR2772372A1 (fr) * 1997-12-15 1999-06-18 Rhodia Chimie Sa Procede de o-alkylation de composes aromatiques hydroxyles
WO2010015559A1 (fr) * 2008-08-05 2010-02-11 Basf Se Procédé pour la fabrication de dérivés 4-bromophényliques

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GB9102519D0 (en) 1991-03-27
AU1167492A (en) 1992-09-07

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