HK1137736A - Process for the synthesis of hydroxy aromatic acids - Google Patents

Description

Method for synthesizing hydroxy aromatic acid

Technical Field

The present invention relates to the preparation of hydroxy aromatic acids that are valuable for a variety of uses, such as use as intermediates or as monomers for the preparation of polymers.

Background

Hydroxy aromatic acids are useful as intermediates and additives in the preparation of many valuable substances, including pharmaceuticals and compounds which are effective in protecting crops, and also as monomers for the preparation of polymers. For example, salicylic acid (ortho-hydroxybenzoic acid) is used in the preparation of aspirin, and has other pharmaceutical applications. The parabens, known as 4-hydroxybenzoates, are useful as food and cosmetic preservatives. P-hydroxybenzoic acid and 6-hydroxy-2-naphthoic acid may be used as components in the liquid crystal polymer, respectively.

Various methods for the preparation of hydroxybenzoic acids, including 2, 5-dihydroxyterephthalic acid ("DHTA"), are known. Marzin in "Journal fur Praktische Chemie" (1933.138, 103-106) proposed the synthesis of 2, 5-dihydroxyterephthalic acid ("DHTA") from 2, 5-dibromoterephthalic acid ("DBTA") in the presence of copper powder.

Singh et al reported in "journal.indian chem.soc." volume 34, phase 4, pages 321 to 323 (1957) the preparation of products, including DHTA, by condensation of DBTA with phenol in the presence of KOH and copper powder.

Rusonik et al, in "Dalton Trans." (2003, 2024-2028), describe the conversion of 2-bromobenzoic acid to salicylic acid, benzoic acid and diphenolic acid in the presence of various ligands in a reaction catalyzed by Cu (I). Tertiary tetraamines minimize the formation of diphenolic acids when Cu (I) is used.

The synthesis of salicylic acid from 2-chlorobenzoic acid is described by Commom et al in Synthetic Communications (32(13), 2055-59, 2002). A stoichiometric amount of pyridine (0.5 to 2.0 moles per mole of 2-chlorobenzoic acid) is used, such as at least 1.0 mole of pyridine per mole of 2-chlorobenzoic acid. Cu powder can be used as a catalyst with pyridine.

Gelmont et al, Organic Process Research & Development (6(5), 591-596, 2002) and U.S. Pat. No. 5,703,274 describe the preparation of 5-hydroxybromoisophthalic acid by hydrolyzing 5-bromoisophthalic acid and mixtures of 5-bromoisophthalic acid, dibromoisophthalic acid isomers and salts thereof in an aqueous alkaline solution in the presence of a copper catalyst at a temperature of 100 to 270 ℃.

Israel 112,706 discloses a process for the preparation of 4-hydroxyphthalic acid and mixtures of 3-hydroxyphthalic acid and 4-hydroxyphthalic acid by hydrolysis of the corresponding bromophthalic acid in aqueous alkaline solution in the presence of a copper catalyst at temperatures of from 100 to 160 ℃. Examples of disclosed copper catalysts include Cu (O), CuCl₂、Cu₂O、CuO、CuBr₂、CuSO₄、Cu(OH)₂And copper (II) acetate.

Many prior art processes for making hydroxybenzoic acids are characterized by long reaction times, limited conversion resulting in significant productivity loss, or the need to run under pressure and/or at higher temperatures (typically 140 to 250℃.) to achieve reasonable rates and productivity. There is therefore still a need for a process by which hydroxybenzoic acid compounds can be economically prepared; meanwhile, the inherent operation difficulty is low; and in small and large scale operations, as well as in batch and continuous operations, with high yields and high productivity.

Summary of The Invention

One embodiment of the present invention provides a method for preparing a hydroxyaromatic acid represented by the structure of formula I:

(COOH)_m-Ar-(OH)_n

I

wherein Ar is C₆-C₂₀Arylene, n and m each independently have a non-zero value, and n + m is less than or equal to 8, comprising (a) contacting a halogenated aromatic acid represented by the structure of formula II with a base in water, thereby forming in water a corresponding m-basic salt of the halogenated aromatic acid,

(COOH)_m-Ar-(X)_n

II

wherein each X is independently Cl, Br, or I, and Ar, n, and m are as described above; (b) contacting the corresponding m-basic salt of the halogenated aromatic acid with a base in water and with a copper source in the presence of a ligand that coordinates to copper to form an m-basic salt of the hydroxy aromatic acid from the m-basic salt of the halogenated aromatic acid at a solution pH of at least about 8; (c) optionally, separating the m-basic salt of the hydroxyaromatic acid from the reaction mixture in which the m-basic salt of the hydroxyaromatic acid is formed; and (d) contacting the m-basic salt of the hydroxy aromatic acid with an acid, thereby forming the n-hydroxy aromatic acid.

In another embodiment, the ligand may be an amine ligand, the ratio of molar equivalents of ligand to molar equivalents of hydroxyaromatic acid is less than or equal to about 0.1, and/or when the ligand is a tetraamine, it comprises at least one primary or secondary amino group.

Another embodiment of the present invention provides a process for preparing an n-alkoxy aromatic acid, which comprises preparing an n-hydroxy aromatic acid in the manner described above and then converting the n-hydroxy aromatic acid into an n-alkoxy aromatic acid.

Thus, another embodiment of the present invention provides a process for preparing an n-alkoxy aromatic acid represented by the structure of formula VI:

(COOH)_m-Ar-(OR⁹)_n

VI

wherein Ar is C₆-C₂₀Arylene radical, each R⁹Independently is substituted or unsubstituted C_1-10An alkyl group, n and m are each independently nonzero values, and n + m is less than or equal to 8, comprising (a) contacting a halogenated aromatic acid represented by the structure of formula II with a base in water, thereby forming in water the corresponding m-basic salt of the halogenated aromatic acid,

(COOH)_m-Ar-(X)_n

II

wherein each X is independently Cl, Br, or I, and Ar, n, and m are as described above; (b) contacting the corresponding m-basic salt of the halogenated aromatic acid with a base in water and with a copper source in the presence of a ligand that coordinates to copper to form an m-basic salt of the hydroxy aromatic acid from the m-basic salt of the halogenated aromatic acid at a solution pH of at least about 8; (c) optionally, separating the m-basic salt of the hydroxyaromatic acid from the reaction mixture in which the m-basic salt of the hydroxyaromatic acid is formed; (d) contacting an m-basic salt of a hydroxy aromatic acid with an acid, thereby forming an n-hydroxy aromatic acid represented by the structure of formula I,

(COOH)_m-Ar-(OH)_n

I

wherein Ar, n and m are as described above; and (e) converting the n-hydroxy aromatic acid to an n-alkoxy aromatic acid represented by the structure of formula VI, wherein Ar, R⁹N and m are as described above.

Another embodiment of the present invention provides a method for preparing 2, 5-dihydroxyterephthalic acid or 2, 5-dialkoxyterephthalic acid as described above, further comprising the step of subjecting the 2, 5-dihydroxyterephthalic acid or 2, 5-dialkoxyterephthalic acid to a reaction to thereby produce a compound, monomer, oligomer or polymer.

Thus, another embodiment of the present invention provides a method for preparing a compound, monomer, oligomer or polymer by preparing a hydroxy aromatic acid represented by the structure of formula I,

(COOH)_m-Ar-(OH)_n

I

wherein Ar is C₆-C₂₀Arylene, n and m each independently have a non-zero value, and n + m is less than or equal to 8, comprising (a) contacting a halogenated aromatic acid represented by the structure of formula II with a base in water, thereby forming in water a corresponding m-basic salt of the halogenated aromatic acid,

(COOH)_m-Ar-(X)_n

II

wherein each X is independently Cl, Br, or I, and Ar, n, and m are as described above; (b) contacting the corresponding m-basic salt of the halogenated aromatic acid with a base in water and with a copper source in the presence of a ligand that coordinates to copper to form an m-basic salt of the hydroxy aromatic acid from the corresponding m-basic salt of the halogenated aromatic acid at a solution pH of at least about 8; (c) optionally separating the m-basic salt of the hydroxy aromatic acid from the reaction mixture in which the m-basic salt of the hydroxy aromatic acid is formed; (d) contacting an m-basic salt of a hydroxy aromatic acid with an acid, thereby forming an n-hydroxy aromatic acid; (e) optionally, converting the n-hydroxy aromatic acid to an n-alkoxy aromatic acid; and (f) subjecting the n-hydroxy aromatic acid and/or the n-alkoxy aromatic acid to a reaction to thereby produce a compound, monomer, oligomer or polymer.

Detailed Description

The present invention provides a high yield and high productivity process for the preparation of hydroxy aromatic acids represented by the structure of formula I

(COOH)_m-Ar-(OH)_n I

The process comprises contacting a halogenated aromatic acid represented by the structure of formula II with a base to form an m-basic salt of the halogenated aromatic acid;

(COOH)_m-Ar-(X)_n II

contacting an m-basic salt of a halogenated aromatic acid with a base and with a copper source in the presence of a ligand that coordinates to copper to form an m-basic salt of an n-hydroxy aromatic acid; the dibasic salt of the n-hydroxy aromatic acid is then contacted with an acid to form the n-hydroxy aromatic acid product.

In the formulae I and II, Ar is C₆-C₂₀Arylene, n and m are each independently a non-zero value, and n + m is less than or equal to 8; and in formula II, each X is independently Cl, Br, or I. Arylene groups represented by "-Ar-" are multivalent aryl groups formed by removing two or more hydrogens on different carbon atoms on an aromatic ring, or when the structure is polycyclic, by removing two or more hydrogens on different carbon atoms on multiple aromatic rings. Thus, the potential for arylene formation is, for example, that hydrogens may be removed from two up to all six carbon atoms on a benzyl ring, or hydrogens may be removed from any two and up to eight positions on one or both rings of a naphthyl group.

Arylene "Ar" may be substituted or unsubstituted. When unsubstituted, an arylene group is a monovalent group containing only carbon and hydrogen. However, in arylene, one or more O or S atoms may optionally replace any one or more catenated or ring carbon atoms, provided that the resulting structure does not contain an-O-or-S-moiety, and provided that no carbon atom is bonded to more than one heteroatom. One example of a suitable arylene group is phenylene as shown below.

As used herein, the term "m-basic salt" is a salt formed from an acid that contains m acid groups with replaceable hydrogen atoms in each molecule.

Various halogenated aromatic acids to be used as starting materials in the process of the present invention are commercially available. For example, 2-bromobenzoic acid is available from Aldrich Chemical Company (Milwaukee, Wisconsin). However, it can be synthesized by oxidation of bromomethylbenzene, as described by Sasson et al in the Journal of Organic Chemistry (1986, 51(15), 2880-2883). Other useful halogenated aromatic acids include, but are not limited to, 2, 5-dibromobenzoic acid, 2-bromo-5-nitrobenzoic acid, 2-bromo-5-methylbenzoic acid, 2-chlorobenzoic acid, 2, 5-dichlorobenzoic acid, 2-chloro-3, 5-dinitrobenzoic acid, 2-chloro-5-methylbenzoic acid, 2-bromo-5-methoxybenzoic acid, 5-bromo-2-chlorobenzoic acid, 2, 3-dichlorobenzoic acid, 2-chloro-4-nitrobenzoic acid, 2, 5-dichloroterephthalic acid, and 2-chloro-5-nitrobenzoic acid, all of which are commercially available.

Other halogenated aromatic acids which may be used as starting materials in the process of the present invention include those shown in the left column of the following table, wherein X ═ Cl, Br or I, and wherein the corresponding hydroxy aromatic acid thus prepared by the process of the present invention is shown in the right column:

in step (a), a halogenated aromatic acid is contacted with a base in water, thereby forming the m-basic salt of the corresponding halogenated aromatic acid. In step (b), the m-basic salt of the halogenated aromatic acid is contacted with a base in water and with a copper source in the presence of a ligand that coordinates to copper to form an m-basic salt of the hydroxy aromatic acid from the m-basic salt of the halogenated aromatic acid.

The base used in step (a) and/or step (b) may be an ionic base, and in particular may be hydrogen for one or more of Li, Na, K, Mg or CaOne or more of an oxide, carbonate, bicarbonate, phosphate or hydrogen phosphate. The base used may be water soluble, partially water soluble, or the solubility of the base may increase as the reaction proceeds and/or as the base is consumed. NaOH and Na are preferred₂CO₃However, other suitable organic bases may be selected, for example selected from: trialkylamines (such as tributylamine); n, N' -tetramethylethylenediamine; and N-alkyl imidazoles (e.g., N-methyl imidazole). In principle, any base which is capable of maintaining the pH above 8 and/or which is capable of binding to the acid formed during the reaction of the halogenated aromatic acid is suitable.

The specific amount of base to be used in step (a) and/or (b) depends on the strength of the base. In step (a), the halogenated aromatic acid is preferably contacted with at least about m equivalents of water-soluble base per equivalent of halogenated aromatic acid. In this context, for a base, an "equivalent" is used as the number of moles of base that react with one mole of hydrogen ions. For an acid, one equivalent is the number of moles of acid that provide one mole of hydrogen ions.

In step (b), sufficient base should be used to maintain the solution pH at least about 8, or at least about 9, or at least about 10, and preferably between about 9 and about 11. Thus, in step (b), the dibasic salt of the halogenated aromatic acid is typically contacted with at least about n equivalents of base, such as a water soluble base, per equivalent of the m-basic salt of the halogenated aromatic acid.

In an alternative embodiment, however, it is desirable to use a total of at least about n + m +1 equivalents of base (such as a water-soluble base) in the reaction mixture in steps (a) and (b) per equivalent of the halogenated aromatic acid initially used at the start of the reaction. The base used in the amounts described above is typically a strong base and is typically added at ambient temperature. The base used in step (b) may be the same as or different from the base used in step (a).

As noted above, in step (b) the m-basic salt of the halogenated aromatic acid is also contacted with a copper source in the presence of a ligand that coordinates to copper. The copper source and ligand may be added to the reaction mixture sequentially or may be mixed separately (e.g., in a solution of water or acetonitrile) and added together. The copper source is mixed with the ligand in water in the presence of oxygen, or may be mixed with a solvent mixture comprising water.

In the presence of the reaction mixture with the copper source and the ligand, in an alkaline solution of the m-basic salt of the halogenated aromatic acid, an aqueous mixture is obtained comprising the m-basic salt of the hydroxy aromatic acid, the copper species, the ligand and the halide salt. If desired, the m-basic salt of the hydroxy aromatic acid may be separated from the mixture at this step and prior to the acidification in step (d) [ as optional step (c) ] and used as the m-basic salt in another reaction or for other purposes.

The m-basic salt of the hydroxy aromatic acid is then contacted with an acid in step (d) to convert it to the hydroxy aromatic acid product. Any acid of sufficient strength to protonate the m-basic salt is suitable. Examples include, but are not limited to, hydrochloric acid, sulfuric acid, and phosphoric acid.

The reaction temperature of steps (a) and (b) is preferably between about 40 and about 120 ℃, more preferably between about 75 and about 95 ℃; the method in various embodiments thus involves the step of heating the reaction mixture. Typically, the solution is cooled before the acidification of step (d) is carried out. In various embodiments, oxygen may be removed during the reaction.

The copper source being copper metal [ "Cu (0) ]"]One or more copper compounds or a mixture of copper metal and one or more copper compounds. The copper compound may be a Cu (I) salt, a Cu (II) salt, or a mixture thereof. Examples include, but are not limited to, CuCl, CuBr, CuI, Cu₂SO₄、CuNO₃、CuCl₂、CuBr₂、CuI₂、CuSO₄And Cu (NO)₃)₂. The copper source may be selected according to the nature of the halogenated aromatic acid used. For example, if the starting halogenated aromatic acid is bromobenzoic acid, CuCl, CuBr, CuI, Cu₂SO₄、CuNO₃、CuCl₂、CuBr₂、CuI₂、CuSO₄And Cu (NO)₃)₂Can be included inAnd (6) selecting. If the starting halogenated aromatic acid is chlorobenzoic acid, then CuBr, CuI, CuBr₂And CuI₂May be included in the available selections. For most systems, CuBr and CuBr₂Is generally the preferred option. The amount of copper used is typically from about 0.1 mol% to about 5 mol% based on moles of halogenated aromatic acid.

When the copper source is Cu (0), copper bromide and the ligand may be combined together in the presence of air. For Cu (0) or Cu (i), predetermined amounts of metal and ligand may be combined in water, and the resulting mixture may be reacted with air or dilute oxygen until a colored solution is produced. The resulting metal/ligand solution is added to a reaction mixture comprising an m-basic salt of a halogenated aromatic acid and a base in water.

The ligand may be a linear or branched chain or cyclic, aliphatic or aromatic, substituted or unsubstituted amine, or a mixture of two or more such ligands. Whether forming compounds, oligomers, or polymers, conventional nomenclature may be employed to describe the number of amine groups present in the ligand, such as mono-, di-, tri-, tetra-, penta-, hexa-, hepta-, or octaamine, and the like. In its unsubstituted form, the ligand may be an organic amine containing only carbon, nitrogen and hydrogen atoms. In their substituted forms, the amine ligands may contain heteroatoms such as oxygen or sulfur. In various embodiments, particularly but not exclusively those involving tetraamines, the amine may comprise at least one primary or secondary amino group.

Primary or secondary monoamines suitable for use as ligands herein include those that can be represented by formula 11

Wherein R is¹And R²Each independently selected from

H；

C₁-C₁₀A linear or branched, saturated or unsaturated, substituted or unsubstituted hydrocarbon group;

C₃-C₁₂a saturated or unsaturated, substituted or unsubstituted, cyclic aliphatic hydrocarbon group; or

C₆-C₁₂Substituted or unsubstituted aromatic hydrocarbon groups.

In certain embodiments, R¹And/or R²It may be, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl or phenyl. In other embodiments, R¹And R²At least one of which is not H. Monoamines particularly suitable for use as ligands herein include ethylamine, isopropylamine, sec-butylamine, dimethylamine, methylethylamine, ethyl-N-butylamine, allylamine, cyclohexylamine, N-ethylcyclohexylamine, aniline, N-ethylaniline, toluidine and dimethylaniline.

Primary or secondary diamines suitable for use as ligands herein include those represented by formula 12

Wherein each R¹And each R²Independently is

H；

C₁-C₁₀A linear or branched, saturated or unsaturated, substituted or unsubstituted hydrocarbon group;

C₃-C₁₂a saturated or unsaturated, substituted or unsubstituted, cyclic aliphatic hydrocarbon group; or

C₆-C₁₂Substituted or unsubstituted aromatic hydrocarbon groups;

wherein R is³And R⁴Each independently is

H；

C₁-C₁₀A linear or branched, saturated or unsaturated, substituted or unsubstituted hydrocarbon group;

C₃-C₁₂a saturated or unsaturated, substituted or unsubstituted, cyclic aliphatic hydrocarbon group; or

C₆-C₁₂Substituted or unsubstituted aromatic hydrocarbon groups; or

R³And R⁴Taken together to form a ring structure, said ring structure being

C₄-C₁₂A saturated or unsaturated, substituted or unsubstituted aliphatic hydrocarbyl ring structure; or

C₆-C₁₂A substituted or unsubstituted aromatic hydrocarbyl ring structure; and is

Wherein a, b and c are each independently 0 to 4.

In certain embodiments, one or two R are¹Is H. In other embodiments, one or two R are²Also referred to as H. In other embodiments, any one or more R¹To R⁴It may be methyl, ethyl, propyl, butyl, pentyl, hexyl or phenyl.

In various particular embodiments, a, b, and c can all be equal to 0, and R³＝R⁴H or R³And R⁴Taken together to form an aliphatic ring structure. Especially when b ═ 0, the aliphatic ring structure may be cyclohexylene, which is a divalent group-C shown below₆H₁₀-, thereby providing a cyclohexyl diamine:

the general formula R can be illustrated by the following structures³And R⁴Form aCyclohexyl:

wherein R is¹、R²A and c are as described above. In alternative embodiments, however, one amino group or alkyl group having an amino group attached thereto may be positioned meta or para to the cycloalkyl or another amino group on the aromatic ring.

Suitable aliphatic diamines may include N, N '-di-N-alkyl ethylene diamine and N, N' -di-N-alkyl cyclohexane-1, 2-diamine. Specific examples include, but are not limited to, N '-dimethylethylenediamine, N' -diethylethylenediamine, N '-di-N-propylethylenediamine, N' -dibutylethylenediamine, N '-dimethylcyclohexane-1, 2-diamine, N' -diethylcyclohexane-1, 2-diamine, N '-di-N-propylcyclohexane-1, 2-diamine, and N, N' -dibutylcyclohexane-1, 2-diamine. Examples of suitable aromatic diamines include, but are not limited to, 1, 2-phenylenediamine and N, N ' -dialkylphenylenediamines, such as N, N ' -dimethyl-1, 2-phenylenediamine and N, N ' -diethyl-1, 2-phenylenediamine; and benzidine.

Tertiary and higher primary or secondary amines suitable for use as ligands herein may be represented by formula 13:

wherein R is¹、R²、R³、R⁴、R⁵And R⁶Each independently selected from:

H；

C₁-C₁₀a linear or branched, saturated or unsaturated, substituted or unsubstituted hydrocarbon group;

C₃-C₁₂a saturated or unsaturated, substituted or unsubstituted, cyclic aliphatic hydrocarbon group; or

C₆-C₁₂Substituted or unsubstituted aromatic hydrocarbon groups; and is

Wherein a is 2 to 4, b and c are each independently 0 to 4; and m is more than or equal to 0.

In certain embodiments, one or two R are¹Or at least one R³Or at least one R⁴Or R⁵And/or R⁶Is H. In other particular embodiments, m is 0, 1, 2, 3, 4 or 5. In other embodiments, R³＝R⁴＝R⁵H; and/or one or two R¹And R²H. In other embodiments, any one or more R¹To R⁶It may be methyl, ethyl, propyl, butyl, pentyl, hexyl or phenyl.

Amines conforming to formula 13 suitable for use as ligands herein include, for example, those represented by formula 14:

wherein x is 2 to 10. Formula 14 describes polyvinylamines wherein in formula 13 each R group is H, a ═ 2, b ═ c ═ 0, and m ═ 0 to 8.

Other amines according to formula 13, or other higher amines suitable for use as ligands herein include diethylenetriamine and triethylenetetramine, as well as those that may be summarized by the following structures:

the ligand may also be a cyclic amine compound, which is a molecule having at least one closed ring structure in which at least one ring atom is nitrogen. The ligand in this form is then heterocyclic in the sense that the ring structure will contain, in addition to the nitrogen atom, other atoms, principally carbon and hydrogen atoms, but which may also be oxygen and/or sulfur, as described below. The nitrogen atom may be, for example

C₄-C₁₂Atoms in a saturated or unsaturated, substituted or unsubstituted aliphatic hydrocarbyl ring structure; or

C₅-C₁₂Atoms in a substituted or unsubstituted aromatic hydrocarbyl ring structure.

Examples of various nitrogen-containing cyclic compounds suitable for use as ligands herein include, but are not limited to, quinolinones, indoles, imidazoles, ethylenimines, and those that can be represented by the following structures:

pyridine compound

Piperidine derivatives

1, 2-di (4-pyridyl) ethane

Bipyridine

1, 10-phenanthroline

The "hydrocarbyl" referred to in the description of the ligands applicable herein above is a monovalent group comprising only carbon and hydrogen in the unsubstituted state. Similarly, an unsubstituted amine is a compound that contains only nitrogen, carbon, and hydrogen atoms in its structure. However, in any of the above hydrocarbon or ring structures, one or more O or S atoms may optionally replace any one or more catenated or ring carbon atoms, provided that the resulting structure does not contain an-O-or-S-moiety, and provided that no carbon atom is bonded to more than one heteroatom. Examples of suitable ligands in which an oxygen atom replaces a carbon atom are shown in formula 15:

wherein q may have an average value of, for example, about 3 in a mixture of molecules having different molecular weights.

Other examples of ligands suitable for use herein and substituted with oxygen include anisidine, phenetole, and those generally represented by the following structures:

ligands with unique versatility include secondary amines, especially N, N' -substituted 1, 2-diamines, including those which can be described as R⁷NH-(CHR⁸CHR⁹)-NHR¹⁰Wherein R is⁷And R¹⁰Each independently selected from C₁-C₄Primary alkyl radical, and R⁸And R⁹Each independently selected from H and C₁-C₄Alkyl, and/or wherein R⁸And R⁹May be joined together to form a ring structure.

In formula 12, when R³And R⁴Taken together to form an aromatic ring structure and/or when the cyclic amine ligand contains one or more aromatic ring structures, more vigorous reaction conditions (e.g., higher temperatures, or greater amounts of copper and/or ligand) are required to achieve high conversion, selectivity, yield, and/or purity of the reaction.

Ligands suitable for use herein may be selected as any one or more members, or all members, of the overall ligand population described by name or structure above. However, suitable ligands may also be selected as any one or more members, or all members, of a subgroup of the entire population, wherein the subgroup may be of any size (e.g., 1, 2, 6, 10, or 20), and wherein the subgroup is formed by omitting any one or more members of the entire population as described above. Thus, in this case, the ligand may be selected not only as one or more or all members of any subgroup of any size formed from the entire population of ligands as described above, but also in the absence of members omitted from the entire population when forming the subgroup. For example, in certain embodiments, the ligands useful herein may be selected as one or more members, or all members, of a subgroup of ligands that excludes pyridine, 2, 5, 8, 11-tetramethyl-2, 5, 8, 11-tetraazadodecane, and/or 1, 1, 4, 7, 10, 10-hexamethyltriethylenetetramine from the overall group, and also excludes, or does not exclude other ligands from the overall group.

In various embodiments, the ligand may be provided in an amount of from about 1 to about 8, preferably from about 1 to about 2, molar equivalents of ligand per mole of copper. In those and other embodiments, the ratio of molar equivalents of ligand to molar equivalents of halogenated aromatic acid may be less than or equal to about 0.1. As used herein, the term "molar equivalent" refers to the number of moles of ligand that will interact with one mole of copper.

In one embodiment, the cu (i) salt may be selected from CuBr; the ligand is selected from: n, N '-dimethylethylenediamine, N' -diethylethylenediamine, N '-di-N-propylethylenediamine, N' -dibutylethylenediamine, N '-dimethylcyclohexane-1, 2-diamine, N' -diethylcyclohexane-1, 2-diamine, N '-di-N-propylcyclohexane-1, 2-diamine, N' -dibutylcyclohexane-1, 2-diamine; and mixing CuBr with two molar equivalents of ligand in the presence of water and air.

The ligand is believed to facilitate the function of the copper source as a catalyst and/or the copper source and ligand are believed to act together to act as a catalyst to improve one or more properties of the reaction.

The above process also enables the efficient and effective synthesis of related compounds, such as n-alkoxy aromatic acids, which may be represented by the structure of formula VI:

(COOH)_m-Ar-(OR⁹)_n

VI

wherein Ar, m and n are as described above, andeach R⁹Independently is substituted or unsubstituted C_1-10An alkyl group. When unsubstituted, R⁹Are monovalent radicals containing only carbon and hydrogen. However, in any such alkyl group, one or more O or S atoms may optionally replace any one or more carbon atoms in the chain, provided that the resulting structure does not contain an-O-or-S-moiety, and provided that no carbon atom is bonded to more than one heteroatom.

The n-hydroxy aromatic acid, as prepared by the process of the present invention, may be converted to an n-alkoxy aromatic acid, and this conversion may be effected, for example, by contacting the hydroxy aromatic acid under basic conditions with a compound of formula (R)⁹)_nSO₄Is achieved by the n-alkyl sulfates of (a). One suitable method of carrying out this conversion reaction is described in austria patent 265,244. Suitable basic conditions for this conversion are a solution pH of at least about 8, or at least about 9, or at least about 10, and preferably from about 9 to about 11, achieved using one or more bases as described above.

In certain embodiments, it is desirable to separate the n-hydroxy aromatic acid from the reaction mixture in which it is produced prior to converting the n-hydroxy aromatic acid to the n-alkoxy aromatic acid.

The above process also enables the efficient and effective synthesis of products made from the resulting 2, 5-dihydroxyterephthalic acid or 2, 5-dialkoxyterephthalic acid, such as compounds, monomers, oligomers or polymers thereof. These resulting materials may have one or more ester, ether, amide, imide, imidazole, carbonate, acrylate, epoxide, urethane, acetal, and anhydride functional groups.

Representative reactions involving materials made by the process of the present invention or derivatives of such materials include, for example, as disclosed in US3,047,536 (which is incorporated herein in its entirety for all purposes), under nitrogen, at 0.1% ZN₃(BO₃)₂In the presence of a solution of 2, 5-dihydroxy naphthaleneTerephthalic acid and diethylene glycol or triethylene glycol. Similarly, U.S. Pat. No. 2, 5-dihydroxyterephthalic acid, suitable for copolymerization of a diacid and a diol to produce a thermally stable polyester, is disclosed in U.S. Pat. No. 3,227,680 (which is incorporated in its entirety as part of this document for all purposes), where representative conditions involve formation of a prepolymer in the presence of a solution of titanium tetraisopropoxide in butanol at 200 to 250 ℃ followed by solid phase polymerization at 280 ℃ and a pressure of 0.08 mmHg.

As disclosed in US 5,674,969 (which is incorporated in its entirety herein for all purposes), 2, 5-dihydroxyterephthalic acid has been polymerized with tetraaminopyridine trihydrochloride monohydrate in strong polyphosphoric acid under slow heating to above 100 ℃ up to about 180 ℃ and reduced pressure, and then precipitated in water; or as disclosed in U.S. provisional application 60/665,737 (which is incorporated herein in its entirety for all purposes) filed on 28.3.2005 as published as WO 2006/104974, the polymerization described above is achieved by mixing the monomers at a temperature of about 50 ℃ to about 110 ℃, then forming oligomers at 145 ℃, followed by reacting the oligomers at a temperature of about 160 ℃ to about 250 ℃. The polymer thus obtainable may be a pyridobisimidazole-2, 6-diyl (2, 5-dihydroxyp-phenylene) polymer, such as a poly (1, 4- (2, 5-dihydroxy) phenylene-2, 6-pyrido [2, 3-d: 5, 6-d' ] bisimidazole) polymer. However, the pyridobisimidazole moiety thereof may be replaced by any one or more of a benzodiimidazole, a benzodithiazole, a benzodioxazole, a pyridobisthiazole and a pyridobisoxazole; and the 2, 5-dihydroxyparaphenylene moiety may be replaced by a derivative of one or more of isophthalic acid, terephthalic acid, 2, 5-pyridinedicarboxylic acid, 2, 6-naphthalenedicarboxylic acid, 4' -diphenyldicarboxylic acid, 2, 6-quinolinedicarboxylic acid, and 2, 6-bis (4-carboxyphenyl) pyridobisimidazole.

Examples

The invention is further defined in the following examples. It should be understood that these examples, while indicating preferred embodiments of the invention, are given by way of illustration only. From the above discussion and these examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

Substance(s): all reagents were used as received. The ligands listed in Table 1 (designations A to O and R) were obtained from Aldrich Chemical Company (Milwaukee, Wisconsin). Ligand P was obtained from TCI America (Portland, Oregon).

TABLE 1：

Ligand numbering	Ligands	Purity (%)
			A	N, N-dimethylethylenediamine	95
B	N, N' -diethyl ethylenediamine	95
			C	N, N' -dimethyl-1, 6-hexanediamine	98
D	N, N-diethyl-N' -methylethylenediamine	97
			E	1, 2-phenylenediamines	98

F	rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine	97
			G	N-methyl ethylenediamine	95
H	1, 2-di (4-pyridyl) ethane	99
			I	N, N, N ', N' -tetramethylethylenediamine	99
J	Racemic-1, 2-diaminocyclohexane	99
			K	N, N' -dimethylethylenediamine	99
L	1, 10-phenanthroline	99+
			M	Ethylenediamine diacetate	98
N	N, N' -diisopropylethylenediamine	99
			O	1, 1, 4, 7, 10, 10-hexamethyltriethylenetetramine	97
P	(1S, 2S) - (+) -dimethylcyclohexa-1, 2-diamine	95
			R	Bipyridine	＞99

2-Bromobenzoic acid (97% pure), 2, 5-dibromobenzoic acid (96% pure), 2-bromo-5-nitrobenzoic acid (98% pure), 4-bromobenzoic acid (98% pure), 4-chlorobenzoic acid (99% pure), 2, 4-dichlorobenzoic acid (98% pure), 2, 5-dichlorobenzoic acid (97% pure), 2-chloro-5-nitrobenzoic acid (97% pure), 2-bromo-5-methoxybenzoic acid (98% pure), and 5-bromo-2-chlorobenzoic acid (98% pure) were obtained from the Aldrich Chemical Company (Milwaukee, Wisconsin).

2, 5-Dibromoterephthalic acid (95 +% purity) was obtained from the Maybridge Chemical company Ltd. (Cornwall, United Kingdom). 2-bromo-5-methylbenzoic acid and 2-chloro-5-methylbenzoic acid (98% purity) were obtained from Oakwood Products, Inc. (West Columbia, South Carolina, USA). 2-chloro-3, 5-dinitrobenzoic acid (97% pure) was obtained from Avocado Organics (now part of Alfa Aesar under Johnson-Matthey Company, Ward Hill, Massachusetts, USA).

Copper (I) bromide ("CuBr") (98%) and copper (II) bromide ("CuBr") (98%)₂") from Acros Organics (Geel, Belgium). Copper (II) sulfate ("CuSO₄") (98% purity) was obtained from Strem Chemicals, Inc. (Newburyport, Massachusetts, USA).

Acetonitrile (99.8%) and Na₂CO₃(99.5%) from EM Science (Gibbstown, New Jersey).

As used herein, the term "conversion" refers to the amount of reactants consumed, expressed as a percentage or portion of theoretical amount. The term "selectivity" of a product P relates to the mole fraction or mole percentage of P in the final product mixture. Thus, the conversion multiplied by the selectivity is equal to the maximum "yield" of P; the actual or "net" yield is typically slightly less than this because sample loss can occur during operations such as separation, handling, drying, etc. The term "purity" refers to the percentage of the isolated sample obtained that is actually the specified substance.

As used in the examples, the term "15% HCl" means an aqueous hydrochloric acid solution having a concentration of 15 grams of HCl per 100mL of solution. Similarly, "35% HCl" means a concentration of 35 grams HCl per gram100mL of aqueous hydrochloric acid. As used in the examples, the term "H₂O "and" water "refer to distilled water. Purity of the product is determined by¹H NMR determination.

The abbreviations have the following meanings: "h" represents hour, "min" represents minute, "mL" represents milliliter, "g" represents gram, "mg" represents milligram, "mmol" represents millimole, "M" represents mole, "NMR" represents nuclear magnetic resonance spectroscopy, "CONV" represents conversion (percent), "SEL" represents selectivity (percent), "T" represents temperature, and "T" represents time.

Example 1

2.00g (9.95mmol) 2-bromobenzoic acid was reacted with 10g H under nitrogen₂And (4) mixing the materials. Then 1.11g (10.45mmol) Na were added₂CO₃. The mixture was heated to reflux for 30min with stirring, still under nitrogen atmosphere. An additional 1.58g (14.92mmol) Na was added₂CO₃Added to the reaction mixture and refluxed for 30 min. Under nitrogen, 22mg of CuBr were added₂And 28mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) with 2mL of H₂O mixed to obtain a dark purple solution. This solution was added via syringe to the stirred reaction mixture at 80 ℃ under nitrogen and stirred for 1h at 80 ℃. After cooling to 25 ℃, the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered and washed with water. After drying, a total of 1.34g (9.7mmol, 98% yield) of salicylic acid was collected. By¹H NMR determined the purity to be about 99%.

Example 2

7.82g (50mmol) of 2-chlorobenzoic acid are reacted with 31g H under nitrogen₂And (4) mixing the materials. Then 6.62g (62.5mmol) Na was added₂CO₃. The mixture was heated to reflux for 30min with stirring, still under nitrogen atmosphere. Under nitrogen, 36mg of CuBr and 79mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) were each reacted with 1mL of H₂And (4) mixing the materials. In the skyThe resulting mixture was stirred under atmosphere until the CuBr dissolved, yielding a dark purple solution. This solution was added via syringe to the stirred reaction mixture at 80 ℃ under nitrogen and stirred for about 3h at 100 ℃ and via¹The reaction was monitored by H NMR. Table 3 shows the distribution of the starting materials and the products at different reaction times. Product selectivity of greater than 99% was observed. After the reaction was completed, the mixture was cooled to 25 ℃, and the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered, washed with water, and dried to obtain 6.00g of 2-hydroxybenzoic acid (85% yield). The filtrate was extracted with ethyl acetate and evaporated to dryness to obtain another 0.65g of 2-hydroxybenzoic acid, resulting in a total yield of 6.65g (48.2mmol, 96% yield).

TABLE 3

Procedure of example 2

Example 3 (comparative example)

7.82g (50mmol) of 2-chlorobenzoic acid are reacted with 31g H under nitrogen in general in accordance with the method described by Comdom et al (supra)₂And (4) mixing the materials. 10.37g (75mmol) of K are added₂CO₃4.04g pyridine (about 51mmole) and 0.25g copper powder, and the mixture is heated back with stirring for about 3 hours. By¹The reaction was monitored by H NMR. Table 4 shows the distribution of the starting materials and products at different reaction times. Depending on the reaction time, a product selectivity of between 82% and 92% was observed. After the reaction was completed, the mixture was cooled to 25 ℃, and the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered, washed with water, and dried to obtain 5.60g of a mixture of 2-hydroxybenzoic acid (74 mol%), 2-chlorobenzoic acid (19 mol%), and benzoic acid (7 mol%). The filtrate was extracted with ethyl acetate and evaporated to dryness to obtain additional0.72g of the same product, giving a total crude yield of 6.32 g. The net yield of 2-hydroxybenzoic acid amounted to 33.6mmol (67%).

TABLE 4

Procedure of example 3

Example 4

2.00g (9.95mmol) 2-bromobenzoic acid was reacted with 10g H under nitrogen₂And (4) mixing the materials. Then 1.11g (10.45mmol) Na were added₂CO₃. The mixture was heated to reflux for 30min with stirring, still under nitrogen atmosphere. An additional 1.58g (14.92mmol) Na was added₂CO₃Added to the reaction mixture and refluxed for 30 min. 14mg of CuBr and 28mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) were each mixed with 1mL of acetonitrile under nitrogen. The resulting mixture was stirred under an air atmosphere until CuBr dissolved to obtain a blue solution. This solution was added via syringe to the stirred reaction mixture at 80 ℃ under nitrogen and stirred for 2h at 80 ℃. After cooling to 25 ℃, the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered and washed with water. After drying, a total of 1.34g (9.7mmol, 98% yield) of salicylic acid was collected. By¹Purity > 99% as determined by HNMR.

Example 5

Example 5 was carried out in the same manner as example 1, but with the same amount of CuSO₄To replace CuBr₂. After drying, a total of 1.30g (9.4mmol, 95% yield) of salicylic acid was collected. By¹HNMR determined the purity to be about 99%.

Example 6, example 7 (comparative example)

2mmol of 2-bromobenzoic acid and 3mmol of Na are reacted under nitrogen at 80 deg.C₂CO₃The solution was stirred until all the acid was dissolved. Followed by the addition of 0.01mmol of CuBr and 0.02mmol of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (example 6, ligand F) or 0.01mmol of 1, 1, 4, 7, 10, 10-hexamethyltriethylenetetramine [ example 7 (comparative example), ligand O ]]1mL acetonitrile and the reaction mixture was heated at 80 ℃ for 3 h. After cooling to ambient temperature, the reaction mixture was carefully acidified with 35% aqueous HCl. The product was isolated by filtration, washed with water and dried under vacuum. The filtrate was extracted with ethyl acetate and evaporated to dryness. By¹The crude reaction product was analyzed by H NMR (d 6-dmso). The results summarized in Table 5 demonstrate that tertiary tetraamine [ ligand O (comparative example) in example 7 compares to the N, N' -substituted 1, 2-diamine ligand (ligand F) used in example 6]With poor performance.

TABLE 5

Examples 6 and 7

Examples	2-bromobenzoic acid	2-hydroxybenzoic acid	Net yield
				6	0％	＞99％	96％
7 (comparative example)	95％	＜5％	＜5％

Examples 8 to 23

2mmol of halogen-substituted benzoic acid shown in Table 6 were reacted with 3mmol of Na under nitrogen at 50 to 75 deg.C₂CO₃The solution was stirred until all the halogen substituted benzoic acid was dissolved. Then 0.02mmol of CuSO is added₄And 0.04mmol of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) in 1mL of deionized water, and the reaction mixture was heated at 80 to 100 ℃ for 4 h. After cooling to ambient temperature, the reaction mixture was carefully acidified with 35% aqueous HCl.

In separation method a, the product was extracted twice from the aqueous layer with ethyl acetate, the ethyl acetate fractions were combined, and the crude reaction product was isolated by vacuum distillation of ethyl acetate. In isolation method B, the product is isolated by filtration, washing with water and vacuum drying. By¹The crude reaction product was analyzed by H NMR (d 6-dmso). The results are summarized in table 6.

TABLE 6

Examples 8 to 23

Temperature separation CONV SEL

EXAMPLES starting materials halobenzoic acid benzoic acid products

(. degree. C.) method (%)

82, 5-dibromo-2-hydroxy-5-bromo-80B > 99

92-bromo-5-nitro-2-hydroxy-5-nitro-80B > 99

102-bromo-5-nitro-2-hydroxy-5-nitro-100A > 99

112-bromo-5-methyl-2-hydroxy-5-methyl-80B > 99

122-bromo-5-methyl-2-hydroxy-5-methyl-100A > 99

134-bromo-4-hydroxy-100A > 99

144-chloro-4-hydroxy-80B > 99

152, 4-dichloro-2-hydroxy-4-chloro-100A 70 > 99

162, 5-dichloro-2, 5-dihydroxy-80B 93 > 99

172-chloro-5-nitro-2-hydroxy-5-nitro-100A 74 > 99

2-chloro-3, 5-dinitro-2-hydroxy-3, 5-dinitro

18 100 A ＞99 ＞99

Radical-

2-chloro-3, 5-dinitro-2-hydroxy-3, 5-dinitro

19 80 B ＞99 ＞99

Radical-

202-chloro-5-methyl-2-hydroxy-5-methyl-100A > 99

2-hydroxy-5-methoxy

212-bromo-5-methoxy-100A > 99

Base-

2-hydroxy-5-methoxy

222-bromo-5-methoxy-80B > 99

Base-

232-chloro-5-bromo-2-hydroxy-5-bromo-80B 73 > 99

Example 24

1.86g (10.0mmol) 2-chloro-4-methylbenzoic acid are reacted with 10g H under nitrogen₂And (4) mixing the materials. Then 1.11g (15mmol) Ca (OH)2 are added. The mixture was heated at 85 ℃ for 60 minutes with stirring, still under nitrogen. 43mg of CuBr and 94mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) were mixed with 1mL of deionized water, respectively, under nitrogen. In the skyThe resulting mixture was stirred under atmosphere until the CuBr dissolved to give a blue solution. This solution was added via syringe to the stirred reaction mixture at 80 ℃ under nitrogen and stirred for 24h at 80 ℃. After cooling to 25 ℃, the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered and washed with water. After drying, a total of 1.45g (9.5mmol, 95% yield) of 2-hydroxy-4-methylbenzoic acid was collected. By¹Purity > 99% as determined by H NMR.

Example 25

The same procedure as described in example 24 was carried out, but using 2.45g (10.0mmol)

4-Bromoisophthalic acid as reactant and 2.70g (25.5mmol) Na₂CO₃Instead of Ca (OH) 2. A total of 1.49g (8.2mmol, 82% yield) of 4-hydroxyisophthalic acid was collected. By¹Purity was 88% as determined by HNMR.

Example 26

The same procedure as described in example 25 was carried out, but using 2.01g (10.0mmol) 4-bromobenzoic acid as reactant and 16mg CuSO₄As a copper source. A total of 1.13g (7.76mmol, 81% yield) of 4-hydroxybenzoic acid was collected. By¹H NMR determined 90% purity.

Example 27

The same procedure as described in example 1 was carried out, but using 12.25g (50.0mmol) of 2-bromoterephthalic acid as reactant and 31g H₂O, 9.94g (94mmol) of Na in total₂CO₃35mg of CuBr as copper source and 79mg of ligand F. A total of 7.9g (39mmol, 78% yield) of 2-hydroxyterephthalic acid was collected. By¹H NMR determined 97% purity.

Example 28

2.00g (8.51mmol) of 2, 5-dichloroterephthalic acid were reacted with 10g of terephthalic acid under nitrogenH₂And (4) mixing the materials. Then 0.938g (8.85mmol) Na was added₂CO₃. The mixture was heated to reflux for 30min with stirring, still under nitrogen atmosphere. An additional 1.31g (12.34mmol) Na was added₂CO₃Added to the reaction mixture and refluxed for 30 min. 12mg of CuBr and 24mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) were each reacted with 2mL of H under nitrogen₂And (4) mixing the materials. The resulting mixture was stirred under an air atmosphere until CuBr dissolved, yielding a dark purple solution. This solution was added via syringe to the stirred reaction mixture at 80 ℃ under nitrogen and stirred for 20h at 80 ℃. After cooling to 25 ℃ the reaction mixture was acidified with HCl (concentrated) to obtain a dark yellow precipitate. The yellow precipitate was filtered and washed with water. After drying, a total of 1.59g (8.03mmol, 94% yield) of 2, 5-dihydroxyterephthalic acid was collected. By¹H NMR determined 95% purity.

Example 29

2.00g (9.95mmol) of 3-bromobenzoic acid are reacted with 10g H under nitrogen₂And (4) mixing the materials. Then 1.11g (10.45mmol) Na were added₂CO₃. The mixture was heated to reflux for 30min with stirring, still under nitrogen atmosphere. An additional 1.58g (14.92mmol) Na was added₂CO₃Added to the reaction mixture and refluxed for 30 min. 14mg of CuBr and 28mg of rac-trans-N, N' -dimethylcyclohexane-1, 2-diamine (ligand F) were mixed with 2mL of water, respectively, under nitrogen. The resulting mixture was stirred under an air atmosphere until CuBr dissolved to obtain a blue solution. This solution was added to the stirred reaction mixture via syringe at 80 ℃ under nitrogen. The temperature was increased to obtain a stable reflux and stirring was continued for 25 h. After cooling to 25 ℃, the reaction mixture was acidified with 15% HCl to obtain a white precipitate. The white precipitate was filtered and washed with water.¹H NMR analysis showed 78% conversion and 100% selectivity to 3-hydroxybenzoic acid. The overall yield was determined to be 78%.

Examples 30 to 32

Reaction of 10mmol of 2-bromobenzoic acid with 12.5mmol of Na at 50 to 75 ℃ under nitrogen₂CO₃10mL of H₂The O solution was stirred until all the halogen substituted benzoic acid was dissolved. Subsequently, 0.01mmol of a copper source (CuBr or CuSO as shown in Table 7) was added₄) And 0.02mmol of ligand F or ligand R dissolved in 1mL of deionized water with stirring in air (as shown in table 7); and the reaction mixture was heated at a temperature and for a time as indicated in table 7. After cooling to ambient temperature, the reaction mixture was acidified with 35% aqueous HCl. The product was isolated by filtration, washed with water and dried under vacuum. By¹The crude reaction product was analyzed by H NMR (d 6-dmso). The results are summarized in table 7.

TABLE 7

Examples 30 to 32

Examples 33 to 48; example 49 (comparative example)

To a 2mL vial equipped with a magnetic stir bar, under nitrogen, was added 25mg (0.077mmol) of 2, 5-dibromoterephthalic acid ("DBTA"), followed by 0.308mL (0.308mmol) of 1.0M aqueous sodium hydroxide and 0.169mL (0.169mmol) of 1.0M aqueous sodium acetate. The mixture was then treated with 0.003mL (0.00077mol, 1 mol%) of a 0.23M solution of copper (I) bromide in acetonitrile and 0.003mL (0.00154mmol, 2 mol%) of a diamine ligand as shown in Table 8 below. For example 50 (comparative example), no ligand was used. The reaction vial was then sealed under nitrogen and placed in a sealed reactor capsule. After 3 hours at 90 ℃, the reaction mixture was cooled to room temperature. The reaction mixture was acidified with 15% aqueous HCl to obtain a precipitate. Filtering the precipitate with H₂O washing and is prepared from¹H NMR analysis of the dried product. The percentage of dbta (ii) conversion for each ligand is shown in table 8. The selectivities for dhta (i) and intermediate 2-bromo-5-dihydroxyterephthalic acid (VII) are also shown in table 8.

TABLE 8

Examples 33 to 49

It should be understood that where an embodiment of the invention is stated or described as comprising, including, containing, having, encompassing or encompassing some feature, unless explicitly stated or described to the contrary, one or more features other than those explicitly stated or described may also be present in the embodiment. An alternative embodiment of the invention, however, may be stated or described as consisting essentially of certain features, wherein embodiment features that would materially alter the principle of operation or the distinguishing characteristics of the embodiment would not be present therein. Another alternative embodiment of the invention may be stated or described as consisting essentially of certain features, in which embodiment or insubstantial variations thereof only the features specifically stated or described are present.

Where the indefinite article "a" or "an" is used to recite or describe a step present in a method of the present invention, it is to be understood that the use of such indefinite article does not limit the number of steps present in the method to one unless a statement or description to the contrary is explicitly provided.

Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. When defining a range, it is not intended that the scope of the invention be limited to the specific values recited.

Claims (22)

1. A process for preparing a hydroxy aromatic acid represented by the structure of formula I

(COOH)_m-Ar-(OH)_n

I

Wherein Ar is C₆-C₂₀Arylene, n and m each independently being a nonzero value, and n + m being less than or equal to 8, the process comprising the steps of:

(a) contacting a halogenated aromatic acid represented by the structure of formula II with a base in water, thereby forming in water the corresponding m-basic salt of said halogenated aromatic acid

(COOH)_m-Ar-(X)_n

II

Wherein each X is independently Cl, Br, or I, and Ar, n, and m are as described above;

(b) contacting the m-basic salt of the halogenated aromatic acid with a base in water and with a copper source in the presence of an amine ligand that coordinates to copper to form an m-basic salt of a hydroxy aromatic acid from the m-basic salt of the halogenated aromatic acid at a solution pH of at least about 8, wherein the ratio of molar equivalents of ligand to molar equivalents of hydroxy aromatic acid is less than or equal to about 0.1 and when the ligand is a tetraamine, the ligand comprises at least one primary or secondary amino group;

(c) optionally, separating the m-basic salt of the hydroxyaromatic acid from the reaction mixture in which it is formed; and

(d) contacting the m-basic salt of the hydroxyaromatic acid with an acid, thereby forming an n-hydroxyaromatic acid.

2. The process according to claim 1 wherein in step (a) said halogenated aromatic acid is contacted with at least about two standard equivalents of water-soluble base per equivalent of halogenated aromatic acid.

3. A process according to claim 1 wherein in step (b) said m-basic salt of a halogenated aromatic acid is contacted with at least about two standard equivalents of water-soluble base per equivalent of m-basic salt of said halogenated aromatic acid.

4. The process according to claim 1 wherein in steps (a) and (b) a total of about n + m +1 normal equivalents of water soluble base per equivalent of said halogenated aromatic acid is added to said reaction mixture.

5. The method of claim 1, wherein the copper source comprises a Cu (0), Cu (I) salt, Cu (II) salt, or a mixture thereof.

6. The process according to claim 1, wherein the copper source is selected from the group consisting of: CuCl, CuBr, CuI, Cu₂SO₄、CuNO₃、CuCl₂、CuBr₂、CuI₂、CuSO₄、Cu(NO₃)₂And mixtures thereof.

7. The method according to claim 1, wherein the ligand comprises a monoamine, diamine, triamine, or tetraamine.

8. The method of claim 1, wherein the ligand comprises an N, N' -substituted diamine.

9. The process according to claim 7, wherein the ligand comprises N, N '-di-N-alkylethylenediamine or N, N' -di-N-alkylcyclohexa-1, 2-diamine.

10. The method according to claim 1, wherein the ligand is selected from the group consisting of: n, N '-dimethylethylenediamine, N' -diethylethylenediamine, N '-di-N-propylethylenediamine, N' -dibutylethylenediamine, N '-dimethylcyclohexane-1, 2-diamine, N' -diethylcyclohexane-1, 2-diamine, N '-di-N-propylcyclohexane-1, 2-diamine, and N, N' -dibutylcyclohexane-1, 2-diamine.

11. The method of claim 1, wherein the ligand comprises cyclohexyl diamine.

12. The method according to claim 1, wherein the ligand comprises a cyclic amine.

13. The method according to claim 1, wherein the ligand is selected from the group consisting of: piperidine, bipyridine, 1, 10-phenanthroline, and 1, 2-bis (4-pyridyl) ethane.

14. A process according to claim 1, further comprising the step of mixing the copper source and the ligand prior to adding them to the reaction mixture.

15. A process according to claim 8 wherein the copper source comprises CuBr.

16. The method according to claim 1, wherein the amount of copper provided is between about 0.1 and about 5 mol% based on moles of halogenated aromatic acid.

17. The method according to claim 1, wherein the ligand is provided in an amount of about one to about two molar equivalents per mole of copper.

18. A process according to claim 1, further comprising the step of converting the n-hydroxy aromatic acid to an n-alkoxy aromatic acid.

19. The method according to claim 18, wherein said n-hydroxy aromatic acid is contacted under basic conditions with a compound having the formula R⁹R¹⁰SO₄Of dialkyl sulfates of (4), wherein R⁹And R¹⁰Each independently is substituted or unsubstituted C_1-10An alkyl group.

20. The method according to claim 1, further comprising the step of subjecting the n-hydroxy aromatic acid to a reaction to thereby produce a compound, monomer, oligomer or polymer.

21. The method of claim 20 wherein the polymer produced comprises a pyridobisimidazole-2, 6-diyl (2, 5-dihydroxyp-phenylene) polymer.

22. The method according to claim 18, further comprising the step of subjecting the n-alkoxy aromatic acid to a reaction to thereby prepare a compound, monomer, oligomer or polymer.