WO2015067494A1

WO2015067494A1 - Process for providing dihalogen substituted salicylic acid derivatives

Info

Publication number: WO2015067494A1
Application number: PCT/EP2014/072990
Authority: WO
Inventors: Eric George KLAUBER; Michael Rack; Thomas Zierke; Nicole HOLUB; David Cortes; Gerald SCHMELEBECK; Junmin JI
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 2013-11-08
Filing date: 2014-10-27
Publication date: 2015-05-14
Anticipated expiration: 2016-05-08

Abstract

The present invention relates to a process for providing: a compound of formula (IV): wherein R¹ is hydrogen or -(C₁-C₄)alkyl, R² is -(C₁-C₄)alkyl, and each Hal is an independently selected halogen, the process comprising the step of: Reacting a compound of formula (III) wherein R¹ and Hal are defined as above, and R³ is an alkali metal, in the presence of a Ag(l) compound, a Cu(ll) compound, and a compound selected from Si(OR²)₄ and B(OR²)₃.

Description

Process for providing dihalogen substituted salicylic acid derivatives

The present invention relates to a process for providing dihalogen substituted salicylic acid derivatives. In a preferred embodiment, the present invention provides an improved process for the production of the herbicide dicamba (3,6-dichloro-2-methoxybenzoic acid). Background of the invention

Dicamba is a selective herbicide currently used for treating e.g. corn, wheat or grassland. It kills broadleaf weeds before and after they sprout. The trivial name dicamba refers to the compound 3,6-dichloro-2-methoxybenzoic acid. The estimated global demand for dicamba in 2012 was about 12.000 million tons per year. However, it is expected that the global demand for dicamba will increase significantly.

Dicamba is typically produced on an industrial scale from 2,5-dichlorophenol using carboxyla- tion under Kolbe-Schmitt conditions, methylation and subsequently saponification/acidification. 2,5-Dichorophenol in turn can be obtained from 1 ,4-dichlorobenzene or 1 ,2,4-trichlorobenzene. The synthetic route via 1 ,4-dichlorobenzene involves nitration and subsequent diazotation, and, therefore is undesired for use on an industrial scale. The synthetic route via 1 ,2,4- trichlorobenzene suffers from limited availability of this starting material and from the formation of several byproducts which are formed in the synthesis of 2,5-dichlorophenol.

In order to meet the increasing market demand for compounds such as dicamba, there is a need in the art for alternative processes, involving a reduced number of steps and/or improved yield, for providing dihalogen substituted salicylic acid derivatives, especially including dicamba.

The object of the present invention is to meet the above needs. It is a further object of the present invention to implement the improved process for the synthesis of dicamba on an industrial scale. A further object of the present invention is the provision of a cost effective process for the synthesis of dicamba. Even minor improvements in the yield in reaction sequences for obtaining dicamba would provide a tremendous benefit. For example, an improvement of yield of 1 % would provide an additional annual amount 120 million tons of dicamba.

Summary of the invention

The present invention relates to an improved process for providing dihalogen substituted salicyl- ic acid derivatives using decarboxylative etherification of dihalogenated phtalic acid derivatives. In particular, the present invention relates to a process for providing a compound of formula (IV):

wherein R¹ is hydrogen or -(Ci-C4)alkyl, R² is -(Ci-C4)alkyl, and each Hal is an independently selected halogen. The process comprises the step of:

Reacting a compound of formula (III)

III wherein R¹ and Hal are defined as above, and R³ is an alkali metal, in the presence of a Ag(l) compound, a Cu(ll) compound, and a compound selected from Si(OR²)₄ and B(OR²)3.

In preferred embodiments, the step of reacting the compound of formula (III) is carried out in the further presence of a co-oxidant. The co-oxidant is preferably selected from molecular oxygen (O2), benzoquinone, K2S2O8, Na2S20s, and a peroxyacetic acid ester. More preferably, the co- oxidant is O2. Furthermore, the Ag(l) compound is in preferred embodiments selected from Ag2C03, Ag(l) acetate (AgOAc), and Ag20. More preferably, the Ag(l) compound is Ag2C03.

In another preferred embodiment, the Cu(ll) compound is selected from Cu(ll) acetate, and CuBr2. More preferably, the Cu(ll) compound is Cu(ll) acetate (Cu(OAc)2).

It is further preferred according to the present invention that the compound selected from Si(OR²)₄ and B(OR²)₃ is Si(OR²)₄.

In a further preferred embodiment, the Ag(l) compound is present in an amount of about 0.1 to about 1 .0 molar equivalents per one molar equivalent of the compound of formula (III). More preferably, the Ag(l) compound is present in an amount of about 0.25 to about 1 .0 molar equivalents per one molar equivalent of the compound of formula (III). In a still further preferred em- bodiment, the Ag(l) compound is present in an amount of about 0.25 molar equivalents. It is preferred according to the present invention that the Cu(ll) compound is present in an amount of about 0.1 to about 1.0 molar equivalents per one molar equivalent of the compound of formula (III). More preferably, the Cu(ll) compound is present in an amount of about 0.2 to about 1 .0 molar equivalents per one molar equivalent of the compound of formula (III), still fur- ther preferably in an amount of about 1.0 molar equivalent.

Furthermore, the compound selected from Si(OR²)₄ and B(OR²)3 is preferably present in an amount of about 1 .0 to about 5.0 molar equivalents per one molar equivalent of the compound of formula (III). More preferably, the compound selected from Si(OR²)₄ and B(OR²)3 is present in an amount of about 5.0 molar equivalents. According to preferred embodiments, the co-oxidant is present in an amount of about 0.8 to about 1 .2 molar equivalents per one molar equivalent of the compound of formula (III). More preferably, the co-oxidant is present in an amount of about 1.0 molar equivalent per one molar equivalent of the compound of formula (III). In alternative preferred embodiments, the co- oxidant is O2 and is provided is gaseous form. In these embodiments, which are especially pre- ferred according to the invention, O2 is provided at a pressure of about 100 kPa to about 200 kPa, more preferably about 101.3 kPa.

The above step of reacting the compound of formula (III) is carried preferably out at a temperature of about 100°C to about 160°C. More preferably, the step of reacting the compound of formula (III) is carried out at a temperature of about 1 15°C to about 150°C, still more preferably about 120°C to about 145°C.

Compounds of formula (IV), in which R¹ is -(Ci-C₄)alkyl, can be converted according to the invention to compounds of formula (IV), in which R¹ is hydrogen.

According to the invention, Hal is preferably selected from -F, -CI, -Br and -I, more preferably - CI and -Br, and most preferably -CI. Furthermore, R¹ is selected from hydrogen, methyl and ethyl, more preferably hydrogen. In certain preferred embodiments according to the invention, R¹ is -(Ci-C₄)alkyl, such as methyl or ethyl, in the compound of formula (III), and the resulting compound of formula (IV), in which R¹ is likewise -(Ci-C₄)alkyl, is preferably converted to a compound of formula (IV), in which R¹ is hydrogen. R² is according to the invention preferably selected from methyl and ethyl, more preferably from methyl. Furthermore, R³ is preferably selected from lithium, sodium and potassium, more preferably from sodium and potassium, and most preferably is potassium.

In particular preferred embodiments, the processes according to the present invention are employed for obtaining dicamba. In these preferred embodiments, the compound of formula (IV) finally obtained is

Dicamba

Further preferred embodiments of the present invention are apparent from the following detailed description and the attached claim set.

Detailed Description of the Invention

In the following, illustrative embodiments of the present invention are described in more detail. The term "Hal" or "halogen" when used in the context of the present invention refers to -F, -CI, -Br or -I. Preferably, the halogen is -CI or -Br, more preferably -CI.

The term "OAc" refers in the context of the present invention to an acetate ion -0(0)C-CH3.

The term "-(Ci-C4)alkyl" refers according to the invention to a straight chained or branched aliphatic alkyl residue having one to four carbon atoms, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl or tert-butyl.

The present invention relates to a process for providing a compound of formula (IV), as defined above, comprising the step of: reacting a compound of formula (III), as defined above in the presence of a Ag(l) compound, a Cu(ll) compound, and a compound selected from Si(OR²)₄ and B(OR²)₃.

III IV

Compounds of formula (III), in which R³ is an alkali metal, can be obtained by neutralizing a corresponding carboxylic acid using a suitable base. The base for neutralizing the correspond- ing carboxylic acid is not specifically limited and is preferably selected from alkali metal alkoxides, such as alkali metal (Ci-C4)alkoxides. An especially preferred base is potassium tert- butoxide. The base is typically used in stoichiometric amounts. The resulting alkali metal car- boxylate salts of formula (III) can be isolated or can be prepared in-situ. The Ag(l) compound is according to the invention preferably selected from Ag2C03, Ag(l) acetate (AgOAc), and Ag20, more preferably Ag2C03. The Ag(l) compound is present in an amount of about 0.1 to about 1 .0 molar equivalents per one molar equivalent of the compound of formula (III), more preferably about 0.25 to about 1 .0 molar equivalents. Especially in case a co- oxidant is present, it is possible and preferable to use the Ag(l) compound in substoichiometric amounts. Thus, in a still further preferred embodiment, the Ag(l) compound is present in an amount of about 0.25 molar equivalents.

The Cu(ll) compound is according to the invention preferably selected from Cu(ll) acetate, and CuBr2. More preferably the Cu(ll) compound is Cu(ll) acetate (Cu(OAc)2). The Cu(ll) compound is present in an amount of preferably about 0.1 to about 1 .0 molar equivalents per one molar equivalent of the compound of formula (III), more preferably about 0.2 to about 1.0 molar equivalents, still more preferably in an amount of about 1 .0 molar equivalent.

It is further preferred according to the present invention that the compound selected from Si(OR²)₄ and B(OR²)₃ is Si(OR²)₄. The compound selected from Si(OR²)₄ and B(OR²)₃ is preferably present in an amount of about 1 .0 to about 5.0 molar equivalents per one molar equivalent of the compound of formula (III), more preferably in an amount of about 5.0 molar equivalents.

As mentioned above, the step of reacting the compound of formula (III) according to the invention is preferably carried out in the additional presence of a co-oxidant as defined above. When a co-oxidant is used, substoichiometric amounts of the Ag(l) compound and/or Cu(ll) compound can be used, which is preferable e.g. from the viewpoint of costs. The co-oxidant is preferably selected from molecular oxygen (O2), benzoquinone, K2S2O8, Na2S20s, and a peroxyacetic acid ester, such as peroxyacetic acid tert-butyl ester. More preferably, the co-oxidant is 02.The co- oxidant is preferably present in an amount of about 0.8 to about 1 .2 molar equivalents per one molar equivalent of the compound of formula (III), more preferably about 1 .0 molar equivalent. When O2 is used as the co-oxidant, which is preferred, it is provided at a pressure of about 100 kPa to about 200 kPa, more preferably about 101.3 kPa.

The above step of reacting the compound of formula (III) is carried preferably out at a temperature of about 100°C to about 160°C, more preferably about 1 15°C to about 150°C, still more preferably about 120°C to about 145°C. The step of reacting the compound of formula (I I I) is carried out in solution in an organic solvent. The organic solvent is not particularly limited as long as it does not interfere with the reaction. Preferred solvents include but are not limited to dioxane, 1 ,2-dichloroethane (DCE), acetonitrile, dimethylsulfoxide (DMSO), dimethylformamide (DMF), N-methylpyrrolidone (NMP), N,N- dimethylacetamide (DMA), or Ν,Ν-dimethylpropionamide (DMP), preferably DMF, DMA, or DMP, most preferably DMF.

Compounds of formula (IV), in which R¹ is -(Ci-C4)alkyl, can be converted according to the invention to compounds of formula (IV), in which R¹ is hydrogen. The conversion can be carried out using a suitable base to obtain the corresponding carboxylic acid salts.

For example, alkali metal hydroxides such as NaOH may be employed here. Thus, a composition comprising alkali metal salts, such as sodium salts, are obtained. The alkali metal salt of a compound of formula (IV) is then acidified in aqueous solution using a suitable acid, such as H2SO4 or HCI, preferably HCI, to afford the compound of formula (IV), in which R¹ is hydrogen.

Carboxylic acids corresponding to compounds of formula (I II), in which R¹ and R³ are hydrogen (referred to as compounds of formula (I l ia), wherein Hal is as defined above), can be obtained from readily available materials in reaction steps suitable to be carried out on an industrial scale. For example, compounds of formula (Il ia) can be provided by oxidizing 1 ,4- dihalonaphthalenes of formula (II), wherein Hal is as defined above.

The above conversion may e.g. accomplished using HNO3 as the oxidant. Compounds of formula (Il ia) can be converted to compounds of formula (I II), in which R¹ is hydrogen and R³ is an alkali metal, using a suitable base such as an alkali metal alkoxide as described above.

Thus, in a preferred embodiment, the present invention relates to a process as defined above, wherein the compound of formula (I II) is obtained by oxidizing a compound of formula (I I) and the resulting compound of formula (I l ia) is neutralized with about one molar equivalent of a suitable base such as an alkali metal alkoxide. Furthermore, the compound of formula (II) in turn can be obtained by halogenating naphthalene (referred to as a compound of formula (I)).

The above reaction step can be carried out on an industrial scale, e.g. by aromatic free radical chlorination or bromination.

Thus, in a further preferred embodiment, the present invention relates to a process as defined above, wherein the compound of formula (II) is obtained by halogenating a compound of formu la (I).

Alternatively, compounds of formula (Ilia) can be obtained by reductive dehalogenation from tetrahalophthalic acid anhydride using zinc powder as described in WO 00/05195.

Thus, in a further preferred embodiment, the present invention relates to a process as defined above, wherein the compound of formula (III) is obtained by reductive dehalogenation of tetrahalophthalic acid, and the resulting compound of formula (Ilia) is neutralized with about one molar equivalent of a suitable base such as an alkali metal alkoxide.

Carboxylic acids corresponding to compounds of formula (III), in which R¹ is -(Ci-C4)alkyl (referred to as a compound of formula (1Mb)), can be obtained by dehydrating the above compounds of formula (Ilia) to obtain 3,6-dihalophthalic acid anhydride. For example, compounds of formula (Ilia) may be combined in a suitable solvent such as toluene with catalytic amounts of acid (e.g. p-toluenesulfonic acid) under azeotropic removal of water to obtain 3,6-dihaolphthalic anhydride. Alternatively, the reaction may be carried out with acid chloride forming reagents such as SOC or POC in an inert solvent such as chlorinated solvents at increased temperature. According to a further alternative, the reaction may be accomplished in acetic acid at in- creased temperature. Subsequently, 3,6-dihalophthalic acid anhydride is reacted the with an alcohol of the formula HOR¹ , wherein R¹ is -(Ci-C4)alkyl, to obtain a compound of formula (l l lb), wherein Hal is as defined above and R¹ is -(Ci-C4)alkyl. For example, 3,6-dihalophthalic acid anhydride may be dissolved in an alcohol of formula HOR¹ (e.g. methanol) together with a corresponding alkali metal (Ci-C4)alkoxide (e.g. NaOCHs) at increased temperature. Alternatively, 3,6-dihalophthalic acid anhydride may be dissolved in an alcohol of formula HOR¹ (e.g. methanol) together with catalytic amounts of acid (such as H2SO4 or HCI) at increased temperature.

Compounds of formula (ll lb) can be converted to compounds of formula (I I I), in which Hal is as defined above, R¹ is -(Ci-C4)alkyl and R³ is an alkali metal, using a suitable base such as an alkali metal alkoxide as described above.

Thus, in a further preferred embodiment, the present invention relates to a process as defined above, wherein the compound of formula (II I), in which R¹ is -(Ci-C4)alkyl, is obtained by dehydrating a compound of formula (I l ia), reacting the resulting 3,6-dihalophthalic acid anhydride with an alcohol of the formula HOR¹ , wherein R¹ is -(Ci-C4)alkyl, and neutralizing the resulting compound of formula (l llb) is neutralized with about one molar equivalent of a suitable base such as an alkali metal alkoxide.

In an alternative embodiment, 3,6-dihalophthalic acid can be obtained by reductive

dehalogenation from tetrahalophthalic acid as described in WO 00/05194 under azeotropic removal of water.

As described above, in preferred embodiments according to the present invention, Hal is -CI, is methyl, and R¹ is hydrogen in the finally obtained product. Thus, the present invention provides in preferred embodiments an improved reaction sequence for obtaining dicamba.

In a first step of a possible reaction sequence, naphthalene is chlorinated for obtaining 1 ,4- dichloronaphthalene as described above. Subsequently, 1 ,4-dichloronaphthalene is oxidized using HNO3 as described above to obtain 3,6-dichlorophthalic acid.

1 ,4-Dichloronaphthalene is a compound according to formula (II) of the present invention in which Hal is CI. 3,6-Dichlorophthalic acid is a compound of formula (Ilia) according to the invention in which Hal is CI. Alternatively, 3,6-dichlorophthalic acid may be obtained by reductive dehalogenation of tertachlorophthalic acid. According to this embodiment, tetrachlorophthalic acid (1 equivalent) is combined in water with an alkali metal hydroxide such as NaOH (about 3.6 molar equivalents) and zinc powder (about 3.0 molar equivalents) at a temperature of about 70 to 80°C to afford trichlorophtahlic acid. Trichlorophthalic acid (1 equivalent) in turn can be converted to 3,6- dichlorophthalic acid by reacting with e.g. NaOH (about 6.0 molar equivalents) and zinc powder (about 5.8 molar equivalents) in water at a temperature of about 95 to 100°C.

3,6-Dichlorophthalic acid can be partly neutralized using one molar equivalent of potassium tert- butoxide to provide potassium 2-carboxy-3,6-dichlorobenzoate which then is reacted according to the present invention using Ag2C03, Cu(OAc)2, Si(OCHs)₄ and O2 as described above to obtain after acidification dicamba.

Potassium 2-carboxy-3,6-dichlorobenzoate is a compound of formula (III) according to the present invention in which R¹ is hydrogen, R³ is potassium and Hal is CI. Dicamba is a compound of formula (IV) of the invention.

Alternatively, 3,6-dichlorophthalic acid can be dehydrated and the resulting 3,6-dichlorophthalic acid anhydride can be reacted with methanol to provide 3,6-dichloro-2- (methoxycarbonyl)benzoic acid.

3,6-Dichloro-2-(methoxycarbonyl)benzoic acid is a compound of formula (1Mb) according to the present invention wherein R¹ is methyl.

Alternatively, 3,6-dichlorophthalic acid anhydride can be prepared by reductive dehalogenation from trichlorophthalic acid (which may be obtained as outlined above) under azeotropic removal of water, and subsequently can be reacted with methanol to provide 3,6-dichloro-2- (methoxycarbonyl)benzoic acid. For example, reacting trichlorophthalic acid to provide 3,6- dichlorophthalic acid anhydride can be accomplished with NaOH (about 6 molar equivalents), zinc powder (about 5.8 molar equivalents) in water at about 95 to 100°C, and subsequently add- ing HCI and azeotropic removal of water using toluene at about 1 10°C.

Subsequently, 3,6-dichloro-2-(methoxycarbonyl)benzoic acid is converted to potassium 3,6- dichloro-2-(methoxycarbonyl)benzoate using potassium tert-butoxide, and the resulting product is in turn is reacted according to the present invention using Ag2C03, Cu(OAc)2, Si(OCH3)4 and O2 as described above to obtain after acidification methyl 3,6-dichloro-2-methoxybenzoate. Methyl 3,6-dichloro-2-methoxybenzoate is hydrolyzed as described above to obtain dicamba.

Potassium 3,6-dichloro-2-(methoxycarbonyl)benzoate is a compound of formula (III) according to the present invention in which Hal is CI, R¹ is methyl and R³ is potassium. Methyl 3,6- dichloro-2-methoxybenzoate is a compound of formula (IV) according to the invention in which Hal is CI, R¹ is methyl and R² is methyl.

Claims

1 . A process for providing a compound of formula (IV):

wherein R¹ is hydrogen or -(Ci-C4)alkyl, R² is -(Ci-C4)alkyl, and each Hal is an independently selected halogen, the process comprising the step of:

Reacting a compound of formula

wherein R¹ and Hal are defined as above, and R³ is an alkali metal,

in the presence of a Ag(l) compound, a Cu(ll) compound, and a compound selected from

Si(OR²)₄ and B(OR²)₃.

The process according to claim 1 , wherein the step of reacting the compound of formula (III) is carried out in the further presence of a co-oxidant, preferably selected from O2, benzoquinone, K2S2O8, Na2S20s, and a peroxyacetic acid ester, more preferably O2.

The process according to claim 1 or 2, wherein

(a) the Ag(l) compound is selected from Ag2C03, Ag(l) acetate and Ag20, and prefera

(b) the Cu(ll) compound is selected from Cu(ll) acetate and CuBr2, and preferably is Cu(ll) acetate; and/or

(c) the compound selected from Si(OR²)₄ and B(OR²)₃ is Si(OR²)₄.

4. The process according to any one of claims 1 to 3, wherein the (a) the Ag(l) compound is present in an amount of about 0.1 to about 1 .0 molar equivalents, preferably about 0.25 to about 1.0 molar equivalents, more preferably about 0.25 molar equivalents; and/or

(b) the Cu(ll) compound is present in an amount of about 0.1 to about 1 .0 molar equivalents, preferably about 0.2 to about 1.0 molar equivalents, more preferably about 1 .0 molar equivalent; and/or

(c) the compound selected from Si(OR²)₄ and B(OR²)3 is present in an amount of about 1 .0 to about 5.0 molar equivalents, preferably about 5.0 molar equivalents; and/or

(d) the co-oxidant is present in an amount of about 0.8 to about 1 .2 molar equivalents, preferably about 1 .0 molar equivalent, or in, case the co-oxidant is O2, it is provided at a pressure of about 100 kPa to about 200 kPa, preferably about 101.3 kPa, based on one molar equivalent of the compound of formula (III).

5. The process according to any one of the preceding claims, wherein the step of reacting the compound of formula (III) is carried out at a temperature of about 100°C to about 160°C, preferably about 1 15°C to about 150°C, more preferably about 120°C to about 145°C.

6. The process according to any one of the preceding claims, wherein a compound of formula (IV), in which R¹ is -(Ci-C₄)alkyl, is reacted to obtain a compound of formula (IV), in which R¹ is hydrogen.

7. The process according to any one of the preceding claims, wherein

(a) Hal is selected from -F, -CI, -Br and -I, preferably -CI and -Br, more preferably -CI; and/or

(b) R¹ is selected from hydrogen, methyl and ethyl, more preferably hydrogen; and/or

(c) R² is selected from methyl and ethyl, more preferably methyl; and/or

(d) R³ is selected from lithium, sodium and potassium, more preferably sodium and potassium, most preferably potassium.

8. The process according to any one of the preceding claims, wherein the compound of formula (IV) is 13