JPH02121976A - Production of phthalides - Google Patents

Abstract

PURPOSE:To obtain the title compound used as a synthetic intermediate of an anthracene derivative in high yield under mild reaction conditions with high catalyst activity by using a specific ruthenium catalyst in the catalytic hydrogenation of an aromatic o-dicarboxylic acid. CONSTITUTION:The hydrogenation of an aromatic o-dicarboxylic acid or its anhydride is conducted at 50 to 250 deg.C, preferably at 100 to 200 deg.C using a ruthenium catalyst containing (1) ruthenium, (2) organic phosphine, (3) a conjugate base of an acid lower than 2-pKa, preferably in combination of the ruthenium catalyst with (2) a neutral ligand. The partial hydrogen pressure in the reaction system is usually 0.1 to 100kg/cm<2>, preferably 1 to 10kg/cm<2>. The amount of ruthenium used in the catalyst is 0.001 to 10 moles per 1 liter of the reaction mixture.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing phthalides by hydrogenating aromatic orthodicarboxylic acids or their anhydrides.

[Conventional technology]

Phthalides are important intermediates for the synthesis of naphthalene or anthracene derivatives, and are also used as raw materials for the synthesis of phthalide in quinoline alkaloids. The following ≠ methods are known as methods for producing phthalides.

(Reaction of ortho-lithio-benzyl alcohol with CO, e.g. Hung, T, V, Aust, J.

Chem, 3u J♂j ('J'/)) (11) Chloromethylation reaction of benzoic acid (e.g. Bhattach
arjee D, J, HeterocycleChe
m, /73/j ('♂0)) (ii'i) Reduction reaction of aromatic orthodicarboxylic acids such as phthalic anhydride derivatives (e.g. Taub, D., Teterahedron et al.
21121AIA3 ('4ff)) (1v) Hydrogenation reaction of aromatic orthodicarboxylic acids such as phthalic anhydride derivatives However, in addition to the problem that the (1)t++)cii+ method requires the use of expensive raw materials or reagents, However, there is a drawback in that complicated operations are required to isolate the phthalides. As a method for hydrogenating aromatic dicarboxylic acids such as phthalic anhydride derivatives, for example, a method is known in which phthalides are produced by a hydrogenation reaction in a liquid suspension phase using a nickel-based catalyst.

(For example, Kalenda A, Ann, j♂≠♂7
('jJ)).

However, in systems using such heterogeneous catalysts, the reaction conditions must generally be harsh. / 00 A11I /
Hydrogen pressure of @ or higher is required.

On the other hand, a method for producing phthalides in which the above hydrogenation reaction is carried out using a homogeneous ruthenium catalyst is also known; for example, in US Pat. No. 3,237,127, (RuXn
PRt R9Rs )xLy:) Using a catalyst of the type a
It is described that the hydrogenation reaction is carried out under the conditions of O-μoops1, and US Pat.
It is described that the hydrogenation reaction is carried out using an E-type catalyst.

[Problem to be solved by the invention]

However, while the conventional method using the homogeneous ruthenium catalyst mentioned above has the characteristic that the hydrogenation reaction proceeds under relatively mild conditions, the catalyst activity is at a rather low level and the catalyst life is significantly shortened. Because it is short and uses halogen, it has the fatal problem of corrosion of the reactor.

The present invention solves all of the above-mentioned conventional problems and provides a method for producing phthalides that can hydrogenate aromatic orthodicarboxylic acids such as phthalic anhydride or their anhydrides with unprecedented industrial advantage. purpose.

[Means to solve the problem]

As a result of intensive studies to achieve the above object, the present inventor has developed a method for producing phthalides by hydrogenating aromatic orthodicarboxylic acids or their anhydrides, using: ■ Ruthenium ■ Organic phosphine ■ pKa as a catalyst. The present invention was achieved by discovering that using a ruthenium-based catalyst containing a conjugated base of an acid with a smaller than 2 not only increases the hydrogenation catalyst activity but also has the effect of improving the activity stability of the catalyst. be.

The present invention will be explained in detail below.

Representative examples of the aromatic orthodicarboxylic acid or anhydride thereof used as a raw material in the present invention include those represented by the following general formulas (I) and (I[).

(In the formula, R represents an alkyl group, an atomyl group, a hydroxyl group, an alkoxy group, a halogen atom, an amino group, an amide group, or an ester group, and m represents a number from / to 3) Even compounds into which substituents have been introduced are preferably converted into corresponding phthalides. In particular, when a 3-substituted aromatic orthodicarboxylic acid or a 3-substituted aromatic dicarboxylic acid anhydride is used, carbonyl groups with little steric hindrance are selectively hydrogenated (formula (I[) below).

Specific examples of these aromatic orthodicarboxylic acids or their anhydrides include phthalic acid, methyl phthalic acid, ethyl phthalic acid, phenyl phthalic acid, dimethyl phthalic acid, trimethyl phthalic acid, hydroxyphthalic acid, methoxyphthalic acid, dimethoxyphthalic acid, and chlorphthalic acid. Examples include acids, bromphthalic acid, aminophthalic acid, methoxycarbonylphthalic acid, and acid anhydrides of these phthalic acids.

The catalyst used in the method of the present invention is a ruthenium-based catalyst containing: (1) ruthenium, (2) organic phosphine, (3) a conjugate base of an acid with a pKa of less than 2, and preferably such a ruthenium-based catalyst further contains (1) a neutral ligand. This is what I did.

Here, (2) As ruthenium, both metal ruthenium and ruthenium compounds can be used in the supply form. As the ruthenium compound, ruthenium oxides, hydroxides, inorganic acid salts, organic acid salts, complex compounds, etc. are used. Specifically, ruthenium dioxide, ruthenium tetroxide, ruthenium trihydroxide, ruthenium chloride, ruthenium bromide, ruthenium iodide, ruthenium nitrate, ruthenium acetate, tris(acetylacetone)ruthenium, sodium hexachlororuthenate, dipotassium tetracarbonylruthenate. , pentacarbonylruthenium, cyclopentadienyldicarbonylruthenium, cyfuromotriluponylruthenium, chlorotris(triphenylphosphine)hydridoruthenium, bis(tri-n-butylphosphine)tricarbonylruthenium, dodecacarbonyltriruthenium, tetrahydridodecacarbonyltetraruthenium , dicesium octadecacarbonylhexarthenate, tetraphenylphosphonium undecacarbonylhydridotriruthenate, and the like.

The amount of these metal ruthenium and ruthenium compounds to be used is such that the concentration in the reaction solution is 0.000/~100 mol, preferably 0.000/-100 mol, as ruthenium in reaction solution/liter.
00/~10 moles.

In the method of the present invention, it is necessary to use (2) organic phosphine in addition to (1) ruthenium, which is thought to contribute to controlling the electronic state of ruthenium and stabilizing the active state of ruthenium. Specific examples of such organic phosphines include trialkylphosphines such as trilobylphosphine, trioctylphosphine, and dimethyl-〇-octylphosphine, tricycloalkylphosphines such as tricyclohexylphosphine, and triarylphosphines such as triphenylphosphine. , alkylarylphosphines such as dimethylphenylphosphine, and polyfunctional phosphines such as r-bis(diphenylphosphino)ethane. , O1/~/ 000 mol, preferably /~i
It is in the range of oo moles. In addition, these organic phosphines can be used alone or in the form of a complex with ruthenium,
It is possible to supply it to the reaction system.

In addition, by using a conjugate base of an acid with a pKa of less than 2 as an additional promoter for ruthenium, which constitutes the main catalyst for the hydrogenation reaction of the present invention, it is possible to take advantage of the advantages of ruthenium, which is the main component, and to generate a relatively mild reaction. In addition to allowing the hydrogenation reaction to proceed under such conditions, it is also possible to particularly improve the hydrogenation catalyst activity, activity stability, and selectivity of the target product.

The conjugate base of an acid with a pKa of less than 2 may be one that produces such a conjugate base during catalyst preparation or in the reaction system, and its supply form may include a Brønsted acid with a pKa of less than 2 or various types of such acids. salt etc. are used. Specifically, inorganic acids such as nitric acid, perchloric acid, hydrofluoroboric acid, hexafluorophosphoric acid yl-% abrate @ sulfonic acid, trichloroacetic acid, dichloroacetic acid, trifluoroacetic acid, methanesulfonic acid, toluenesulfonic acid, Dodecyl sulfonic acid, octadecyl sulfonic acid, to! jFluoromethanesulfonic acid, benzenesulfonic acid,
Examples include Brønsted acids such as organic acids such as halatoluenesulfonic acid and sulfonated styrene-divinylbenzene copolymer, and alkali metal salts, alkaline earth metal salts, ammonium salts, and silver salts of these acids.

Furthermore, the conjugate base of these acids may be added in the form of acid derivatives that are thought to be generated in the reaction system. For example, similar effects can be expected even when added to the reaction system in the form of acid nologides, acid anhydrides, esters, acid amides, etc.

The amount of these acids or salts used is 0.0/~/000 mol, preferably 0.7~1 mol, based on ruthenium.
00 mole range.

The ruthenium-based catalyst of the present invention may further contain (1) a neutral ligand.

Such neutral ligands include hydrogen, ethylene, propylene,
Olefins such as furan, cyclopentene, cyclohexene, butadiene, cyclopentadiene, cyclooctadiene, turbonasien; -carbon oxide, diethyl ether, aninol, dioxane, tetrahydrofuran, acetone, acetophenone, benzophenone, cyclohexanone, propionic acid, caproic acid, butyric acid ,benzoic acid,
Oxygenated compounds such as ethyl acetate, allyl acetate, hensyl benzoate, benzyl stearate, valerolactone; nitrogen oxide, acetonitrile, flobionitrile, benzonitrile, cyclohexylisonitrile, butylamine, aniline, toluidine, triethylamine pyrrole, bilicii, N- Methylformamide, acetamide, /, /
, 3. Nitrogen-containing compounds such as 3-tetramethylurea, N-methylpyrrolidone, caprolactam, and nitromethane; carbon disulfide, n-butylmercaptan, thiophenol,
Sulfur-containing compounds such as dimethyl sulfide, dimethyl disulfide, thiophene, dimethyl sulfoxide, diphenyl sulfoxide; tributylphosphine oxyto, ethyldiphenylphosphine oxyto, triphenylphosphine oxyto, diethylphenylphosphinate, diphenylethylphosphinate, diphenylmethylphosphonate, o,o-dimethylmethylphosphonothiolate,
triethyl phosphite, triphenyl phosphite,
triethyl phosphate, triphenyl phosphate,
Examples include phosphorus-containing compounds other than organic phosphines such as hexamethylphosphoric triamide.

The present invention also provides a golden color when reaction raw materials, reaction products, reaction solvents, etc. act as simultaneous trapping neutral ligands.

The ruthenium-based catalyst used in the method of the present invention may be synthesized and isolated in advance. For example, J, ○r
ganometa1. Chem, 77 C-j/(
'74')), or their precursors may be added individually to the reaction system to prepare and use the ruthenium-based catalyst within the reaction system.

Examples of the method for synthesizing the ruthenium-based catalyst of the present invention include:
In halogen-containing ruthenium compounds such as cyclooctadiene dichlororuthenium, dichlorotristriphenylphosphine 7/l/thenium, Y represents a conjugate base of an acid with a pKa of less than 2) (for example, Inorg, Chem, /7/
96! ('l') (see formula exposure).

RuX2 Lm+■' Nigo (RuXLs) +Y-+
MX −・”(IV) (wherein, X represents a halogen such as chlorine or bromine, and represents an organic phosphine or a neutral ligand (
however, it contains one or more organic phosphines). M%Y
has the same meaning as the above definition. ) Also, a ruthenium hydride compound such as dihydridotetrakis(triphenylphosphine)ruthenium, hydridochlorotristriphenylphosphine)ruthenium, or a ruthenium compound that produces a ruthenium hydride compound under hydrogenation reaction conditions has a pKa of less than 2. A method of adding Stead's acid or its salt (onium salt compounds such as ammonium salt, phosphonium salt, sulfonium salt or oxonium salt) (for example, J, Chem, Soc, Dal
tonTrans, 370 ('7j). (see formula V)
RuH2L4 +M'Y2=Go(RuHL< )”Y
-10M'H...(V) (wherein, Y has the same meaning as defined above and represents an onium cation such as M' hafloton, ammonium, phosphonium, sulfonium, oxonium ion, etc.), or A method of treating with a stable carpenium ion salt such as triphenyl rupenium ion or tropylium ion (the counter anion is a conjugate base of an acid with a pKa of less than 2) (for example, fnorg,
Chem, /7 /96! ('7♂), see formula (Vl)).

Ru HI L4 + P h s C" Y-2=Go CRuHLa "l +Y-10 P h sCH...
A catalyst can be prepared according to (■) (in the formula, Y has the same meaning as defined above).

The method of the present invention can be carried out in the absence of a solvent, that is, using the reaction raw material itself as a solvent, but it is also possible to use a solvent other than the reaction raw material. Examples of such solvents include ethers such as diethyl ether, anisole, tetrahydrofuran, ethylene glycol dimethyl ether, and dioxane, ketones such as acetone, methyl ethyl ketone, and acetophenone, methanol, ethanol, n-butanol, benzyl alcohol, phenol, and ethylene glycol. , diethylene glycol
Flucols, carboxylic acids such as formic acid, acetic acid, propionic acid, toluic acid, esters such as methyl acetate, n-butyl acetate, benzyl benzoate, benzene, toluene,
Aromatic hydrocarbons such as ethylbenzene and tetralin, n-
Aliphatic hydrocarbons such as hexane, n-octane and cyclohexane, halogenated hydrocarbons such as dichloromethane, trichloroethane and chlorobenzene, nitro compounds such as nitromethane and nitrobenzene, N,N-dimethylformamide, N,N-dimethylacetamide, N- Carboxylic acid amides such as methylpyrrolidone, hexamethylphosphoric acid triamide, other amides such as N,N,N',N'-tetraethylsulfamide, N,N'-dimethylimidazolitone, N,N,N, N-tetramethylureadenrho
Urea, sulfones such as dimethyl sulfone and tetramethylene sulfone, sulfoxides such as dimethyl sulfoxide and diphenyl sulfoxide, γ-butyrolactone, ε
-Lactones such as caprolactone, polyethers such as tetraglyme (tetraethylene glycol dimethyl ether) and l♂-crown, nitriles such as acetonitrile and benzonitrile, carbonic acid esters such as dimethyl carbonate and ethylene carbonate, etc. .

In order to carry out the hydrogenation reaction according to the method of the present invention, a reaction vessel is charged with a reaction raw material, a catalyst component, and optionally a solvent, and hydrogen is introduced into the reaction vessel. Hydrogen may be diluted with a gas inert to the reaction, such as nitrogen or carbon dioxide.

The reaction temperature is usually jO-2! O”C1 preferably 100
~200°C. The hydrogen partial pressure in the reaction system is usually 0. /
~/θ0#/cr/l, preferably /~10/cr/
It is l. Of course, it is not impossible to carry out the process under lower or higher pressures, but it is not industrially advantageous.

The reaction can be carried out either batchwise or continuously. Required reaction time in case of batch method is usually /-
It is 20 hours.

The target lactones can be recovered from the reaction product liquid by conventional separation and purification means such as distillation and extraction. Further, the distillation residue can be recycled to the reaction system as a catalyst component.

〔Example〕

The present invention will be explained in more detail with reference to examples below, but the present invention is not limited to the following examples unless it exceeds the gist of the present invention.

Example/20 μ (0.0 J-mmol) of ruthenium acetylacetonate was placed in a 70.1 spinner stirring autoclave.
, trioctylphosphine 0.2 ml (0,!;r
rmol), p-toluenesulfonic acid 7Amg (0
, lAmmol) and phthalic anhydride 2 and tetraethylene glycol dimethyl ether/Arxl,
After purging the inside of the autoclave with inert gas, 30 kg of hydrogen was injected at room temperature, and the temperature of the autoclave was raised to 200"C to conduct a reaction for 3 hours. After the reaction, the autoclave was opened,
The product was quantified by gas chromatography. As a result, the yield of phthalide was t%.

Example Core - A similar reaction was carried out using dioxane instead of the 7-tophethylene glycol dimethyl ether used as the solvent in Example.

After the reaction, the solvent was distilled off using an evaporator, and the residue was recrystallized from ether-dichloromethane to obtain the phthalide as a white solid. The yield of phthalide was ♂lA%.

Comparative Example/The same reaction as in Example A was carried out except that the p-1 luenesulfonic acid used in Example A was not used. As a result, the yield of phthalide was O/%.

Example 3 The same reaction as in Example 2 was carried out except that phthalic acid≠7 was used in place of the phthalic anhydride used in Example 2. As a result, the yield of phthalide was about 20%.

Example Hiro Chlorophthalic anhydride used in place of the phthalic anhydride used in Example Ko? As a result of performing the same reaction as in Example λ except that λ was used, the yield of ≠-chlorophthalide was 20%. Trace amounts of phthalide, a dechlorination product, were produced as a by-product.

Example! 70,/! Ruthenium acetylacetonate 20 (O, OS mmol) and trioctylphosphine 4 o...! in a spinner stirring autoclave. rnl (OJmmo
l ), p-toluenesulfonic acid 71 rmg (0,4
tmmol) and 3-hydroxyphthalic anhydride? After purging the inside of the autoclave with an inert gas, hydrogen was introduced under pressure at room temperature, the temperature of the autoclave was raised to 200''C, and the reaction was carried out for 3 hours.

After the reaction, the autoclave was opened, the solvent was distilled off, and the residue was recrystallized from ether-dichloromethane to obtain two white solids.
(Yield to%) was obtained.

The results of elemental analysis confirmed that it was hydroxy-phthalide.

Elemental analysis value; calculation, value C; 6≠, 0, H; ≠, 0 analysis value C; 63. From the results of measurements of Ri, H;

'Hnmr spectrum CH,s, 3. ! ppm(S
) Ar −H7, / r ppm (d), 7, J o
ppm(d)t 7,≠Oppm(t) J=7.4Hz Example 2 Hydrogen pressure j used in Example 2 Hydrogen pressure θ instead of OKG
As a result of carrying out the same reaction as in Example except that KG was used, the yield of phthalide was 67%.

[〆Effects of the invention]

According to the present invention, when preparing phthalides by hydrogenating aromatic orndicarboxylic acid or its anhydride,
Ruthenium of the present invention, organic phosphine and acid dissociation constant p
By carrying out the reaction in a homogeneous liquid phase using a conjugate base of an acid having a Ka of less than 2 as a catalyst, the desired phthalides can be obtained in good yield at a lower cost and under milder conditions than in conventional methods.

Claims (2)

[Claims] (1) In a method for producing phthalides by hydrogenating an aromatic orthodicarboxylic acid or its anhydride in the presence of a catalyst, the catalyst includes [1] ruthenium [2] organic phosphine [3] with a pKa of less than 2. A method for producing phthalides, characterized by using a ruthenium-based catalyst containing a conjugate base of a small acid. (2) Further ruthenium-based catalyst [4] Neutral ligand A patent claim characterized by containing A method for producing phthalides according to scope 1.