WO2001083420A2

WO2001083420A2 - Method of making substituted dihalo aromatic acid chlorides

Info

Publication number: WO2001083420A2
Application number: PCT/GB2001/001917
Authority: WO
Inventors: Michael J. Fifolt; Michael C. Savidakis; Daniel R. Thielen; Ronald F. Spohn; William S. Derwin; David C. Johnson; Sanjay Mandal
Original assignee: Occidental Chemical Corporation; Stephens, Dinah
Priority date: 2000-05-02
Filing date: 2001-05-01
Publication date: 2001-11-08
Also published as: WO2001083420A3; AU5238501A

Abstract

A three-step method of making a substituted dihalo aromatic acid chloride is disclosed. A substituted aromatic compound having the general formula is halogenated to produce a mixture of corresponding dihalo and trihalo aromatic compounds, where R is COOH or COOR', R' is alkyl from C1 to C6, each R1 is independently selected from alkyl or alkoxy from C1 to C6 with no more than a single R1 group in the ortho position, and n is 1 or 2. Ortho halogens are selectively dehalogenated to produce the corresponding monohalo and dihalo aromatic compounds. The dihalo aromatic compound is converted into the corresponding acid chloride.

Description

METHOD OF MAKING SUBSTITUTED DIHALO AROMATIC ACID CHLORIDES

This invention relates to a three-step process for making substituted dihalo aromatic acid chlorides.

According to one aspect of this invention, there is provided a method of making an dihalo acid chloride comprising

(A) halogenating the ring of an aromatic compound having the general formula

to produce a mixture of corresponding dihalo and trihalo aromatic compounds, where R is COOH or COOR', R' is alkyl from C, to C_6l each R, is independently selected from alkyl or alkoxy from C, to C₆, with nα-more than a single R, group in the ortho position, and n is 1 or 2; (B) selectively dehalogenating ortho halogens from said corresponding dihalo and trihalo aromatic compounds in said mixture to produce corresponding monohalo and dihalo aromatic compounds having no ortho halogens; and

(C) converting corresponding dihalo aromatic compound into the corresponding dihalo acid chloride.

R is preferably COOR'.

R' may be alkyl from to C₃, and is preferably methyl.

Conveniently Ri is in the para position.

Preferably i is alkyl from to C₃, and is most preferably methyl.

Conveniently said aromatic compound is chlorinated, and preferably said aromatic compound is halogenated with chlorine gas.

Advantageously said aromatic compound is halogenated using a Lewis acid catalyst and an iodme-containing co-catalyst.

Conveniently no solvent is present during said halogenation.

Preferably a copper catalyst and a carboxylic acid are used during said dehalogenation.

Conveniently an α,α,α-trichloromethyl benzene is used during said conversion. This invention also relates to a method of making a 3,5-dichloro acid chloride comprising

(A) chlorinating an aromatic ester having the general formula

to produce a mixture of the corresponding 3,5-dichloro aromatic ester, the corresponding 2,3-dichloro aromatic ester, the corresponding 2,5-dichloro aromatic ester, and the corresponding 2,3,5-trichloro aromatic ester, where R' is alkyl from C_j to C₃, and R_t is alkyl from C to C₃; (B) selectively dechloriπating said 2,3-dichloro aromatic ester, said 2,5- dichloroaromatic ester, and said 2,3,5-trichloro aromatic ester in said mixture to produce the corresponding 3-chloro aromatic ester and additional 3,5-dichloro aromatic ester, respectively; (C) isolating said corresponding 3,5-dichloro aromatic ester, and

(D) converting said corresponding 3,5-dichloro aromatic ester into the corresponding 3,5-dichloro acid chloride.

Preferably R' is methyl.

Conveniently Ri is methyl.

Preferably said aromatic compound is halogenated using a Lewis acid catalyst and an iodme-containing co-catalyst in the absence of a solvent.

Advantageously a copper catalyst and a carboxylic acid are used during said dehalogenation.

Conveniently an α,α,α-trichloromethyl benzene is used during said conversion.

This invention also relates to a method of making 3,4-dichloro-4-methyl benzoyl chloride comprising

(A) using a Lewis acid catalyst and an iodine-containing co-catalyst in the absence of a solvent, cWorinating methyl-p-tohiate to produce a mixture of 3,5-dichloro-methyl-p-toluate, 2,3-dichloro- methyl-p-tomate, 2,5-dichloro-methyl-p-toluate, and 2,3,5- trichloro-methyl-p-toluate; (B) using a copper catalyst and a carboxylic acid, decMorinating said 2,3-dichloro-methyl-p-toluate, said 2,5-dichloro-methyl-p-toluate, and said 2,3,5-trichloro-methyl-p-toluate in said mixture to produce 3-chloromethyl toluate and additional 3,5-dichloro- methyl-p-toluate; and

(c) using an α,α,α-trichloromethyl benzene, converting said 3,5- dichloro-methyl-p-toluate into 3,5-dichloro-4-methyl benzoyl chloride.

We have discovered that substituted dihalo acid chlorides, such as 3,5- dichloro-4-methyl benzoyl chloride, can be made without the corresponding isomeric dihalo acid chloride in the product mixture. In the three-step process of this invention, an aromatic acid or ester is halogenated, which produces a mixture of the dihalo and trihalo acids or esters, which converts them into mono and dihalo acids o esters. The desired dihalo acid or ester is then converted into the acid chloride. The process of this invention results in a high- purity product, though by a circuitous route.

The starting material for the process of this invention is an aromatic carboxylic acid or ester having the general formula

where R is COOH or COOR', R' is alkyl from C, to C₆, each R, is independently selected from alkyl or alkoxy from Ci to C₆, with no more than a single Ri group in the ortho position, and n is 1 or 2; R is preferably COOR', R' is preferably alkyl from to C₃ and most preferably methyl, i is preferably in the para position and is preferably alkyl from Ci to C₃ and is most preferably methyl, and n is preferably 1 as those compounds are commercially more important, (if n is 2, one Ri group must be ortho to the_^R group). Examples of aromatic compounds that can be used in the process of this invention include methyl-4-methylbenzoate (M4MB), methyl-3-methylbenzoate, methyl-3-amino-benzoate, ethyl-4- ethylbenzoate, and propyl-3-propyl benzoic acid.

Haloqenation The aromatic compound is chlorinated or brominated to produce a mixture of the corresponding dihalo and trihalo aromatic isomers. For example, chlorinating methyl-p-toluate produces a mixture of 2,5-dichloro-methyl-p-toluate, 2,3-dichlαro- methyl-p-toluate, 3,5-dicr.loro-methyl-ρ-toluate, and2_>3_I5-trichloro-methyl-ρ-toluate.

Examples of chlorinating and brominating agents that can be used include chlorine gas, liquid bromine, BrCI, SO₂CI₂, SOCI_Zl COCI₂, C₂O₂Cl₄, C₃O₃CI₆, n- chlorosuccinimide, n-bromosuccinimide, and 1 ,3-dibromo-5,5-dimethylhydantoin. Preferably, the chlorinating agent is chlorine gas and the brominating agent is liquid bromine as they are effective and easier to use. About 1 to about 3 equivalents of chlorinating agent or brominating agent should be used for each chlorine or bromine atom to be added to the aromatic ring. Chlorination is preferred to bromination because the d.c Joro compound are con,.;^",2rcially more important than the dibromo compounds. Any Lewis acid catalyst can be used during halogenation, including aluminum chloride, ferric chloride, antimony (III) chloride, lead (IV) chloride, molybdenum (VI) chloride, thallium (I) chloride, tin (IV) chloride, titanium (IV) chloride, tungsten (VI) chloride, zirconium (IV) chloride, and mixtures thereof. The preferred Lewis acid catalyst is ferric chloride as it is inexpensive, easily removed from the product mixture, and environmentally friendly. About 0.1 to about 10 mole% (based on the aromatic compound) of the ewis acid catalyst can be used; less is less effective and requires a long reaction time and more is unnecessary and offers no additional advantage. The preferred amount of Lewis acid catalyst is about 0.5 to about 5 mole%.

An iodine-containing cocatalyst is also used in the halogenation reaction. Examples of suitable cocatalysts include iodine, ICI, ICI₃, alkali metal iodides, such as sodium iodide or potassium iodide, alkaline earth metal iodides, such as calcium iodide or magnesium iodide, alkyl iodides, where the alkyl group has 1 to 18 carbon atoms and preferably 1 to 6 carbon atoms, such as methyl iodide or ethyl iodide, and aryl iodides, where the aryl group contains 6 to 18 carbon atoms and preferably 6 to 10 carbon atoms, such as phenyl iodide. The preferred cocatalyst is iodine because it is inexpensive, does not form byproducts, and is easy to use as a solid

or in solution. About 0.001 to about 0.1 equivalents of the cocatalyst should be used as less is ineffective and more is unnecessary. The preferred amount of cocatalyst is about 0.005 tc- about 0.05 equivalents. It is preferable to perform the halogenation reaction without a solvent in order to maximize throughput. However, if the desired product is a solid, it may be desirable to use about 5- to about 50 wt% of a solvent such as methylene chloride, chloroform, or dichloroethane to facilitate separation of the product.

The halogenation reaction can be performed at a temperature from about ambient to about 100° C; at lower temperatures the reaction is slower and at higher temperatures byproducts may form. The preferred temperature range is about 40 to about 75°C.

The general procedure for the halogenation reaction is to charge a reactor with all the aromatic compound, all the catalyst and cocatalyst, and some of the chlorinating agent or brominating agent and heat the mixture. Additional chlorinating or brominating agent is added as needed. The reaction is performed at atmospheric pressure.

Dehalogenation

In the dehalogenation reaction, halogens that are ortho to the R group are removed. For example, 2,3-dichloro-rπethyl-p-toluate and 2,5-dϊchloro-methyl toluate produce the 3-chloro-methyl-p-toluate and 2,3,5-trichloro-methyl-p-toIuate produces additional 3,5-dichloro-methyl-p-toluate. Finely-divided elemental copper

can be used to catalyze the dehalogenation reaction. (See U.S. Patent No.

5,886,210, herein incorporated by reference.) About 1 to about 2.5 equivalents of copper should be used as less copper w^'.iϊ leave too much unreacted di- or trihalo aromatic compound and more copper will leave too much unreacted copper. Preferably, about 1.7 to about 2.1 equivalents of copper are used.

A carboxylic acid is also used in the dehalogenation reaction. Preferably, the carboxylic acid is a liquid at the reaction temperature. Examples of carboxylic acids

that can be used include acetic acid, propionic acid, butyric acid, and benzoic acid.

The preferred carboxylic acids are acetic acid and propionic acid as they are

commercially available liquids and are not too malodorous. About 1.5 to about 3.5 equivalents of the carboxylic acid should be used per aromatic compound to be dehalogenated, a$ less is less effective and more is unnecessary and wasteful; preferably, about 1.9 to about 2.1 equivalents are used.

The dehalogenation reaction is best performed at or near the boiling point of the carboxylic acid, but lower temperatures can be used if desired. For propionic acid, the temperature range can be about 100 to about 200^αC, though about 140

to about 170^ύC is preferred. The reaction normally requires about 2 to about 20 hours.

After the dehalogenation reaction is complete, the product mixture is cooled

and water is added in an amount about 1 to about 5 times the weight of the dihalo aromatic compound. Less water may not dissolve all the salts and more water is unnecessary. The preferred amount of water is about 1 to about 2 times the weight

of the substrate. As an example, the product mixture can be cooled to about 80 °C

and hot water in an amount about equal to the substrate weight can be added so

that the resulting temperature of the product mixture is about 40 to about 80°C. If the product differs in density from the density of the aqueous solution

formed by at least about 0.1 g/cc, then no solvent is needed and organic and

aqueous phases will form, with the product in the organic phase and the copper salts in the aqueous phase. (If the product has a high melting point, a solvent can be used to dissolve it.) If the product is methy(-3,5-dichIoro- -methyl beπzoate (DCMMB) and the carboxylic acid is propionic acid, the DCMMB will form a lower phase and the aqueous solution will form the upper phase. If the product does not differ in density from the density of the aqueous solution by at least about 0.1 glee, either a sufficient amount of a dense solvent, such as methylene chloride, chloroform, dichloroethane, or chlorobenzene. should be used so that the solution of the product is at least 0.1 g/cc denser than the aqueous solution, or a sufficient amount of a less dense solvent, such as hexane, toluene, or ethyl acetate, should be used so that the aqueous solution is at least 0.1 g/cc denser than the solution of the product. Alternatively, additional water may be added in order to lower the salt concentration in the aqueous phase, thus lowering its density. Preferably, the difference in densities should be at least about 0.2 g/cc so that the two phases form

quickly. The organic phase can be decanted and washed with water. The purity of the product in the organic phase may be high enough so that distillation is not needed. Elemental copper can be recovered from the aqueous phase by electrolysis. The carboxylic acid can be recovered from the aqueous phase by, for

example, distiliation.

Conversion into Acid Chloride

The dihalo aromatic compound is preferably isolated from any moπohalo aromatic compounds prior to conversion to the acid chloride, as it is usually easier to separate the acids or esters than to separate the acid chlorides. Separation can be accomplished by, for example, distillation. The conversion of the dihalo aromatic compound into the corresponding acid chloride can be accomplished by reacting it with an ct.α.α-trichloromethylbenzene. The amount of α,α,σ- trichloromethylbeπzene used should be about 1 to about 1.4 equivalents as less will leave unreacted dihalo aromatic compound and more may result in the production of unwanted byproducts. Preferably, about 1 to about 1.1 equivalents of the α, , - trichloromethylbenzene are used. A catalyst is also used in this reaction. The amount of catalyst should be about 0.01 to about 0.2 equivalents as less will result in a slower reaction and more is unnecessary and wasteful. The preferred amount of catalyst is about .0.02 to about 0.08 equivalents. Examples of suitable catalysts include ammonium septamolybdate, (NH₄)₆Mo₇p_2<,^«4H₂O (ASM), or ammonium dimolybdate, (NH₄)₂Mo₂O₇-2H₂O (ADM). (The amounts of water of hydration may yary.)

The general procedure is to charge a reactor with the dihalo aromatic compound, the α,α,α-trichIoromethylbenzene, and the catalyst and heat the mixture to about 150 to about 180^DC; the reaction is slower at lower temperatures and at higher temperatures unwanted byproducts may be produced. The preferred temperature is about 155 to about 165°C. No solvent is needed for the reaction.

The reaction is usually complete in about 5 to about 12 hours. The product mixture

contains the corresponding dihalo benzoyl halide and a benzoyl chloride, which can be separated by distillation.

The following examples further illustrate this invention. In these examples,

EDC is ethylene dichloride, I is methyl-3-chloro-4-methylbenzoate, II is methyl-3,5- dichloro-4-methylbenzoate, 111 is methyl-2,5-dichloro-4-methylbenzoate, IV is methyI-2,3-dichloro-4-methylbenzoate, and V is methyl-2,3,5-trichloro^- methylbenzoate.

Examples 1 to 7 The following table gives the conditions and results:

r-

The above experiments show that significant dichlorination did not occur when no iodine-containing catalyst was used.

Examples 8 to 16 Examples 1 to 7 were repeated using 30 g of methyl-3-chloro- - methylbenzoate, 25 wt% EDC, and a temperature of 40 °C. The following table gives the conditions and results:

>

^"co co

Q- ε o

The above experiments show that the rate of chlorinatioπ of I is very low when extremely low levels (0.001 equiv.) Of FeCI₃ are employed. They also show that acceptable rates can be obtained when 0.003 to 0.005 equiv. of FeCI₃ are used if

>0.002 equiv. of l₂ are also used.

Example _.17 - Comparative

4MB (3720 g) was chlorinated with chlorine using 2.49 mole% of FeCI₃ at atmospheric pressure. During the initial stages of the chlorination, the temperature was kept below 40^ώC. Solids began to form after 8.5 hr, however, necessitating an

increase in temperature to 60° C. After 21.2 hr, the reaction mixture remained solid at 60'C. An analysis of a sample of the mixture by gas chromatαgraphy (GC) indicated that 94% of the M4MB had been chlorinated to give 98.2% methyl-3- chloro-4-methylbeπzoate with small amounts of dichlorϊπated methyl- -

methylbeπzoates along with side-chain chlorinated by-products.

Examples 8 to 23

In each of the following examples the amount of M4MB chlorinated was 600

g. These reactions were carried out in a jacketed 1 L reactor with mechanical

stirring. The solvent employed in these reactions was 1 ,2-dichloroethaπe (EDC) and

the reaction temperature was maintained at 25 to 32 ° C using a> chiller. The following table gives the reaction conditions:

The following table gives the chlorinated ester product distribution:

The above examples show that similar product distributions can be obtained using differing amounts of FeCI₃ and l₂ and that the appropriate reaction conditions can be chosen based on desired cycle time, heat transfer limitations, or other manufacturing parameters.

Example 24 To 200 g of a mixture of chlorinated 4-methylmethylbenzoates ( MB) was added 33.8 g of propionic acid and 27.3 g of copper powder. After heating for 11 hr at 140 to 150 C, the mixture was cooled to 90°C and diluted with 194 g of H₂O. Since there was unreacted copper present, the mixture was filtered. Two phases formed. The lower organic layer was washed with 113 g of \- ₂0 and then with 112 g of 9 wt% Na₂CO₃. The following table gives the composition of the substrate and

product mixtures:

Example 25 Example 24 was repeated using 62.5 g of propionic acid and 48.5 g of copper powder. After heating for 3 hr at 160^ώC, the mixture was cooled to 90^αC and diluted with 128 g of H₂O. Since there was unreacted copper present, the mixture was filtered. Two phases formed. The lower organic layer was washed with H₂O and then with 100 g of 4 wt% ₂CO₃. The following table gives the composition of the substrate and product mixtures:

These examples show that not only is it possible to separate the desired product(s) from the copper salts and the organic acid by diluting with water, but that this method is preferable to precipitating out the copper salts, distilling the organic acid, and subsequently distilling the desired product.

Example 26 Into a reaction vessel was placed 28 g 3,5-dichIoro-4-methyl toluene (DCMT), 25.3 g benzotrichloride (BTC), and 79 mg molybdenum trioxide. The mixture was heated at 164°C and followed by gas chromatography (GC). The reaction started very rapidly, but after 4.5 hours it stopped and an additional 79 mg of molybdenum trioxide had to be added to complete it. After a total of 11.25 hours, the reaction mixture became thick and was stopped. The reaction mixture contained 53 wt% DCTOC, 37 wt% benzoyl chloride, 0 wt% BTC and 8 wt% DCMT. The following table shows the progress of the reaction:

Example 27 Example 26 was repeated using 12 DCMT, 10 g BTC, and 82 mg ADM. After 9 hours an additional 2 g BTC was added. After a total of ten hours the reaction was complete. The reaction mixture contained 43 wt% DCTOC, 36 wt% benzoyl chloride, 18 wt% BTC and 2 wt% DCMT. The following table shows the progress of the reaction:

Example 28 Example 27 was repeated using 290 mg ASM and a temperature of 162°C. After ten hours the reaction was complete. The reaction mixture contained 53 wt% DCTC and 43 wt% benzoyl chloride. The following table shows the progress of the reaction:

A di ional 2 g BTC ad e . In these Examples, when molybdenum trioxide was used the reaction was initially rapid but stopped until additional catalyst was added; when either ADM or ASM was used, the reaction started slowly, then accelerated to completion without the need for additional catalyst. This suggests that the catalytic mechanism of molybdenum trioxide is not the same as the catalytic mechanism of ADM and ASM.

In the present Specification "comprise" means "includes or consists of and "comprising" means "including or consisting of.

The features disclosed in the foregoing description, or the following Claims, or the accompanying drawings, expressed in their specific forms or in terms of a means for perforrning the disclosed function, or a method or process for attaining the disclosed result, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

Claims

WE CLAIM:

1. A method of making an dihalo acid chloride comprising

(A) halogenatiπg the ring of an aromatic compound having the general

formula

to produce a mixture of corresponding dihalo and trihalo aromatic

compounds, where R is COOH or COOR', R' is alkyl from C, to C_6I each R, is independently selected from alkyl or alkoxy from C, to C₆, with nσ more than a single R., group in the ortho position, and n is 1 or 2;

(B) selectively dehalogenating ortho halogens from said corresponding dihalo and trihalo aromatic compounds in said mixture to produce corresponding monohalo and dihalo aromatic compounds having

no ortho halogens; and

A method according to Claim 1 wherein R is COOR'.

A method according to Claim 1 wherein R' is alkyl from C, to C₃.

4. A method according to Claim 3 wherein R' is methyl.

5. A method according to any one of Claims 1 to 4 wherein Ri is in the para position.

6. A method according to any one of Claims 1 to 5 wherein Ri is alkyl

7. A method according to any one of Claims 1 to 6 wherein said Ri is methyl.

8. A method according to any one of Claims 1 to 7 wherein said aromatic compound is chlorinated.

9. A method according to any one of Claims 1 to 8 wherein said aromatic compound is halogenated with chlorine gas.

10. A method according to any one of Claims 1 to 9 wherein said aromatic compound is halogenated using a Lewis acid catalyst and an iodme-containing co-catalyst.

11. A method according to any one of Claims 1 to 10 wherein no solvent is present during said halogenation.

12. A method according to any one of Claims 1 to 11 wherein a copper catalyst and a carboxylic acid are used during said dehalogenation.

13. A method according to any one of Claims 1 to 12 wherein an α,α,α- trichloromethyl benzene is used during said conversion.

14. A method of making a 3,5-dichloro acid chloride comprising (A) chlorinating an aromatic ester having the general formula

to produce a mixture of the corresponding 3,5-dichloro aromatic ester, the corresponding 2,3-dichloro aromatic ester, the corresponding 2,5-dichloro aromatic ester, and the corresponding 2,3,5-trichloro aromatic ester, where R' is alkyl from to C₃, and Ri is alkyl from Ci to C₃-^'

(B) selectively dechlorinating said 2,3-dichloro aromatic ester, said 2,5-dichloraromatic ester, and said 2,3,5-trichloro aromatic ester in said mixture to produce the corresponding 3-chloro aromatic ester and additional 3,5-dichloro aromatic ester, respectively.

(C) isolating said corresponding 3,5-dichloro aromatic ester, and

15. A method according to Claim 14 wherein R¹ is methyl.

16. A method according to Claim 14 or 15 wherein R_t is methyl.

17. A method according to Claim 14, 15 or 16 wherein said aromatic compound is halogenated using a Lewis acid catalyst and an iodme-containing co-catalyst in the absence of a solvent.

18. A method according to any one of Claims 14 to 17 wherein a copper catalyst and a carboxylic acid are using during said dehalogentation.

19. A method according to any one of Claims 14 to 18 wherein an α,α,α- trichloromethyl benzene is used during said conversion.

20. A method of making 3,5-dichloro-4-methyl benzoyl chloride comprising

(A) using a Lewis acid catalyst and an iodme-containing co-catalyst in the absence of a solvent, cWorinating methyl-p-toluate to produce a mixture of 3,5-dichloro-methyl-p-toluate, 2,3-dichloro- methyl-p-toluate, 2,5-dichloro-methyl-p-toluate,m and 2,3,5- trichloro-methyl-p-toluate;

(B) using a copper catalyst and a carboxylic acid, decUorinating said 2,3-dichloro-methyl-p-toluate, said 2,5-dichloro-methyl-p-toluate, and said 2,3,5-trichloro-methyl-p-toluate in said mixture to produce 3-chloromethyl toluate and additional 3,5-dichloro- methyl-p-toluate; and (C) using an α,α,α-trichloromethyl benzene, converting said 3,5- dichloro-methyl-p-toluate into 3,5-dichloro-4-methyl benzoyl chloride.