GB1579151A

GB1579151A - Preparation of diphenyl ether compounds

Info

Publication number: GB1579151A
Application number: GB2383177A
Authority: GB
Original assignee: Croda Synthetic Chemicals Ltd
Current assignee: Croda Synthetic Chemicals Ltd
Priority date: 1977-06-04
Filing date: 1977-06-04
Publication date: 1980-11-12
Also published as: NL7806111A; FR2392950A1; FR2392950B3; JPS543023A

Description

(54) PREPARATION OF DIPHENYL ETHER COMPOUNDS (71) We, CRODA SYNTHETIC CHEMICALS LIMITED, a British Company of Cowick Hall, Snaith, Goole, North Humberside DN14 9AA, do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed, to be particularly described in and by the following statement:- Various processes are known for the production of diaryl ethers. One method comprises condensation of phenol with a compound such as m-cresol in the vapour phase but this tends to suffer from the disadvantage that it usually produces a mixture of products. Another process involves the Ullmann reaction and comprises reacting an alkali metal phenate with a halobenzene in the presence of copper powder or a copper salt.

When bromobenzenes are used the reaction occurs quite speedily at the brominated position but it is recognised that if a chlorobenzene is used it is usually necessary to activate the chlorobenzene by including in the ring an electronwithdrawing group at the ortho or para position. Thus whenever a chlorobenzene has been reacted with a phenate by the Ullmann reaction it usually appears to have been considered essential to have at least one chloro, nitro or trifluoromethyl group in the ortho or para position in the chlorobenzene. Typical Ullmann processes of this type are described in British Patent Specification Nos. 1,052,390; 1,293,540; 1,404,535, and 1,415,945.

Such processes are inevitably restricted to the production of diaryl ethers containing the activating groups and yet there is a great commercial need to make diaryl ethers that do not contain, for instance, o- or p-chlorosubstituents but which instead are unsubstituted or, more preferably, are metasubstituted by alkyl, hydroxyalkyl formyl or carboxyl. Such compounds are useful in the synthesis of, inter alia, pyrethroid insecticides, but commercially these compounds are made, not in a single step from chlorobenzene, but from the much more expensive bromobenzene or by a condensation reaction, with its attendant disadvantages.

It is known to be desirable to conduct the Ullmann reaction in a solvent, aprotic solvents often being used. In British Patent Specification No. 1,415,945 it is stated that a halogenated diaryl ether can be made by an Ullmann reaction conducted in the presence of up to 50 mole % based on the total phenol content of a free phenol, there being no advantage in using more than 50 /OX It is further stated that the reaction temperature must be from 120 to 2000C and preferably from 130 to 1700C.

U.S. Patent Specification No. 2,008,987 discloses the preparation of diphenyl ether by reacting chlorobenzene with an alkali metal phenate in a homogeneous phase in the presence of water, free phenol and, optionally, copper. The reaction is carried out at high pressure (at least 115 atmospheres) and high temperature (300 to 4000 C). The molar ratio of chlorobenzene to phenate is required to be 2:1. U. S.

Patent Specification No. 1,744,961 is another example of a disclosure which involves the Ullmann reaction for the preparation of diphenyl ether in the presence of water under pressure, the specified temperature being between 275 and 375"C., but the presence of free phenol is avoided.

U. S. Patent Specification No. 1,099,761 discloses preparing diphenyl ether or mphenoxytoluene by reacting chlorobenzene with an alkali metal phenate or mcresate, in the presence of an equivalent molar amount of the free phenol or cresol, under pressure and at a temperature of at least 200"C, but apparently in the absence of copper. Hence the reaction is not an Ullmann reaction. In the specific examples, where the molar ratio of chlorobenzene to phenate is always 2:1, no yields are given other than for the preparation of diphenyl ether.

U. S. Patent Specification No. 3,567,781 is a later example of a comparable copperfree process but there is no suggestion that free phenol should be present during the reaction. To the best of our knowledge, reactions of the type described have not proved commercially satisfactory unless a form of copper is used as a catalyst.

We have now suprisingly found that, despite all these indications to the contary, it is possible to make a diaryl ether free of activating groups such as ortho or para chloro by the Ullmann reaction in good yield, without having to go to the expense of using a bromobenzene compound.

According to the present invention, diphenyl ether or a mono-meta- substituted diphenyl ether of the formula

wherein one of R, and R2 is hydrogen and the other is hydrogen, methyl, hydroxymethyl, cyano, formyl, or a group of the formula CH(OR3)2, COOR4 or COOM wherein each R3 is C18 alkyl or the two R3,s together form a chain of 2 to 4 carbon atoms, R4 is C1s alkyl and M is an alkali metal, is prepared by reacting an optionally substituted chlorobenzene of the formula

with an optionally substituted alkali metal phenate of the formula

wherein M, R, and R2 are as defined above, provided that R2 is not COOM, at a temperature above 150"C under substantially an hydros conditions in the presence of copper or a copper salt and, as solvent, more than 50 mole /O of a phenol, based on the amount of the alkali metal phenate.

Preferably the solvent phenol is the free phenol corresponding to the alkali metal phenate used in the reaction. Thus the reaction is preferably conducted by first reacting an alkali metal compound, usually the alkali metal hydroxide, with more than 1.5 molar equivalents of phenol and then reacting the resultant mixture with the chlorobenzene in the pressence of copper or copper salt.

If Rl or R2 is COOM, then the substituent is present as a salt e.g. a sodium or potassium salt. If R, or R2 is COOR4, i.e.

an ester group R4 is preferably of 1 to 4 carbon atoms. If R, or R2 is an acetal group of the formula CH(OR3)2 then as the - R3 groups may be the same or different C1-B alkyl groups and are preferably C14 alkyl groups.

Alternatively, the two R3 groups together may form an alkylene chain of 2 to 4 carbon atoms, in which case R, or R2 may be, for example, an ethylene-dioxymethyl group. Most preferably R3 is ethyl or, especially, methyl.

The preferred R, or R2 substituent is hydroxymethyl, methyl, or COOM wherein M is as defined above. It will be appreciated that any substituents on the reactants used in this invention often provide little or no activation of the reaction.

The amount of free phenol must be at least 50 mole %, but it is found that higher amounts are usually required for satisfactory yields, the amount preferably being at least 60, and usually at least 80, mole OX. Best results are often obtained at amounts of 100 mole % or more, for example 110 to 300 mole %. Amounts of above about 350 mole % tend to give no increased advantages and incur the disadvantage of requiring the recycle of increased amounts of phenol.

The amount of chlorobenzene that is required can vary quite widely, for example from one to 3 moles per mole of the alkali metal phenate. Preferably there is always at least a stoichiometric amount of the chlorobenzene in order to ensure complete reaction of the alkali metal phenate, and in order to promote the desired reaction.

The reaction temperature may be from 150 to 3500C but is preferably at least 170"C and is generally in the range of from 175 to 3500C. There seems to be no advantage in going above 350"C and at 1 500C or below it may be difficult to obtain a commmercially adequate reaction.

Generally therefore minimum temperatures of 200"C, preferably 205"C and more preferably 220"C, are used. The maximum temperature is usually 300"C, and preferably 270"C. Best results are generally obtained at about 220 to 2700C.

The reaction can be conducted under atmospheric pressure, e.g. under reflux, if the reactants boil at sufficiently high temperature. However a particularly preferred feature of the invention resides in conducting the reaction under autogenous pressure, that is to say the reaction is conducted in an autoclave or other closed vessel under the pressure automatically generated as a result of heating the reaction mixture to the chosen reaction temperature.

It is preferred that M is potassium. The potassium phenates have the advantage that they tend to permit adequate reaction at lower temperatures than the sodium phenates. They are usually obtained by reacting potassium hydroxide with the chosen phenol. The reaction mixture is substantially anhydrous during the Ullmann reaction and so if, as preferred, the alkali metal phenate is generated in situ by reaction of the phenol with potassium hydroxide or other alkali metal compound, it is necessary to remove the water which is formed before conducting the Ullmann reaction. When it is desired that Rl or R2 should be COOM, the desired starting material may be prepared in situ by reacting the alkali metal hydroxide with mchlorobenzoic acid or m-hydroxybenzoic acid, again forming water, which must be removed.

The water may be azeotropically distilled from the mixture, generally forming an azeotrope with the chosen chlorobenzene.

It is desirable to remove all water before the Ullmann reaction is carried out but, by "substantially anhydrous", we generally mean that up to 10, but preferably not more than 5,~mole % of water per mole of the alkali metal phenate can be tolerated.

The copper powder or copper salt may be added before or after the formation of the alkali metal phenate and/or the removal of the water. Copper powder is preferred but any of the salts that can be used for Ullmann condensations may be used, for example the oxides, carbonates, chlorides, bromides and sulphates of monovalent or divilent copper.

The reaction is normally conducted for from 2 to 50 hours and preferably from 12 to 36 hours.

The following Examples illustrate the invention.

Example 1 (R1 is hydrogen, R2 is methyl and M is potassium) 540 g. (5 mol) of m-cresol, 165 g. of 85% potassium hydroxide (2.5 mol KOH), 5 g. of copper powder and 562.5 g. (5 mol) of chlorobenzene were heated to reflux in an autoclave and the resulting water azeotropically removed. The autoclave was then sealed, the temperature adjusted to 250"C and the mixture stirred for 24 hours at this temperature. Work-up involved cooling to 1200C, an addition of 500 ml water to dissolve potassium chloride, filtration to remove copper and acidification with 75 ml concentrated hydrochloric acid to decompose any unreacted potassium m-cresate. The upper organic layer was separated and distilled to yield excess reactants and 340 g. of the product, m-phenoxytoluene:b.p.183 187 /78 Torr (conversion of m-cresol 47%, selectivity 79%, conversion of chlorobenzene 44%, selectivity 84%).

Example 2 (Rl is hydroxymethyl, R2 is hydrogen and M is potassium) 30 g. (0.21 mol) of m-chlorobenzyl alcohol, 59.4 g. (0.63 mol) of phenol, 13.7 g of 85% potassium hydroxide (0.21 mol KOH), 1.0 g. of cuprous bromide and 30 ml of toluene were heated and stirred at reflux.

Water was azeotropically removed and toluene distilled out. The reaction mixture was then heated and stirred at 17-1780C for 24 hours. Work-up involved cooling to 80"C, adding 50 ml of dilute acid and separating the organic layer. Analysis indicated a 38% molar yield of mphenoxybenzyl alcohol.

Example 3 (R1 and R2 are both hydrogen and M is sodium) 423 g. (4.5 mole) of phenol, 60 g. (1.5 mole) of sodium hydroxide, 3 g. of copper powder and 337.5 g. (3 mole) of chlorobenzene were heated to reflux in an autoclave and the resulting water was azeotropically removed. The autoclave was then sealed, the temperature raised to 22-2400C and kept at that level for 24 hours. Work-up involved cooling to 1200, addition of 450 ml water to dissolve sodium chloride, filtration to remove copper and acidification with 50 ml concentrated hydrochloric acid to decompose any unreacted sodium phenate. Analysis of the upper organic layer indicated a 66% molar yield of diphenyl ether (168 g.) based on the sodium phenate taken.

Example 4 (Rl is COOK, R2 is hydrogen and M is potassium) 15.6 g. (0.1 mol) of m-chlorobenzoic acid, 13.2 g. of 85% potassium hydroxide (0.2 mol KOH), 47 g. (0.5 mol) of phenol, 20 ml of water, 100 ml. of toluene and 1 g. of Cu powder were charged to a flask. Water was removed azeotropically with stirring, followed by toluene. The temperature was raised to 165--1700C, and stirring was continued at this level for 10 hr. Work-up and purification yielded 3 - phenoxybenzoic acid in 40% yield.

Example 5 The procedure of Example 1 can be followed with good results by substituting an equivalent amount of m-cyanophenol, m-hydroxybenzaldehyde, methyl m-hydroxy- benzoate, m-dimethoxymethylphenol or m (ethylenedioxymethyl)phenol for the mcresol. The procedure of Example 2 can be followed with good results by substituting m-chlorotoluene, m-cyanochlorobenzene, mchlorobenzaldehyde, a m-(dialkoxymettyl)- chlorobenzene or m-(ethylene- dioxymethyl) chlorobenzene for m chlorobenzyl alcohol.

WHAT WE CLAIM IS: 1. A process for preparing diphenyl ether or a mono-meta substituted diphenyl ether of the formula

wherein one of R1 and R2 is hydrogen and the other is hydrogen, methyl, hydroxymethyl, cyano, formyl or a group of the formula CH(OR3)2, COOR4 or COOM wherein each R3 is C18 alkyl or the two Razzs together form a chain of 2 to 4 carbon atoms, R4 is C18 alkyl and M is an alkali metal, which comprises reacting an optionally substituted chlorobenzene of the formula

with an optionally substituted alkali metal phenate of the formula

wherein M, R, and R2 are as defined above, provided that R2 is not COOM, at a temperature of above 1500C under substantially anhydrous conditions in the presence of copper or a copper salt, and, as solvent, more than 50 mole % of a phenol, based on the amount of the alkali metal phenate.

2. A process according to claim I in which the solvent phenol is of the formula

wherein R2 is as defined in claim I and is the same as the substituent (if any) on the alkali metal phenate.

3. A process according to claim 2 which comprises reacting an alkali metal compound with more than 1.5 molar equivalents of the phenol and then reacting the resultant mixture with the chlorobenzene in the presence of copper or a copper salt.

4. A process according to any preceding claim in which there is from 110 to 300 mole % of the phenol present when the chlorobenzene is reacted with the phenate.

5. A process according to any preceding claim in which one of Rl and R2 is hydrogen and the other is hydroxymethyl, methyl or COOM wherein M is as defined in claim 1.

6. A process according to any preceding claim in which there are from 1 to 3 moles of the chlorobenzene permole of the phenate.

7. A process according to any preceding claim in which M is potassium.

8. A process according to any preceding claim which is carried out in the presence of copper powder.

9. A process according to any preceding claim which is carried out at a temperature of between 150 and 300"C.

10. A process according to claim 9 in which the temperature is between 150 and 270"C.

11. A process according to any preceding claim in which the temperature is at least 170"C.

12. A process according to claim I substantially as described in any of the Examples.

13. An optionally substituted diphenyl ether when prepared by a process according to any preceding claim.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. m-hydroxybenzaldehyde, methyl m-hydroxy- benzoate, m-dimethoxymethylphenol or m (ethylenedioxymethyl)phenol for the mcresol. The procedure of Example 2 can be followed with good results by substituting m-chlorotoluene, m-cyanochlorobenzene, mchlorobenzaldehyde, a m-(dialkoxymettyl)- chlorobenzene or m-(ethylene- dioxymethyl) chlorobenzene for m chlorobenzyl alcohol. WHAT WE CLAIM IS:

1. A process for preparing diphenyl ether or a mono-meta substituted diphenyl ether of the formula

with an optionally substituted alkali metal phenate of the formula

2. A process according to claim I in which the solvent phenol is of the formula

7. A process according to any preceding claim in which M is potassium.