JP2001335571A - Method for producing phthalic anhydride - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for efficiently producing phthalic anhydrides, under mild conditions in a high yield by a simple process and a simple aftertreatment. SOLUTION: This method for producing a phthalic anhydride of formula (I) (R is h, a halogen, NO2, CN, a (halo)1-8C alkyl, a (halo)1-20C alkoxy, a (halo)1-20C alkylthio, phenyl or a substituted phenyl substituted with one or more halogens, 1-6C alkyls, halo 1-6C alkyls or 1-6C alkoxys; n is 0-4; R can exhibit a 4C alkenylene or a 1-2C alkylenedioxy with an adjoining C) is characterized by subjecting a phthalic acid of formula (II) to a dehydration reaction in an inert solvent in the presence of a catalytic amount of an acidic compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing phthalic anhydrides useful as starting compounds for pharmaceuticals, agricultural chemicals, chemicals and the like.

[0002]

2. Description of the Related Art A method for producing phthalic anhydrides is, for example, a method of heating from phthalic acids without solvent (J. Am. Chem. Soc., 77 , 5093,
(1955)) and acetic anhydride (J. Chem. Soc.,
1950 , 2842), methoxyacetylene (ibid., 19
54 , 1860), carbodiimide (J. Am. Che
m. Soc. , 85 , 1997 (1963)) and phosphorus pentoxide (the same, 85 , 2282 (1963 ) ).

[0003]

In the prior art, the method of heating without a solvent requires a high temperature, and the method of using a dehydrating agent involves an expensive reaction reagent, and the amount of the reagent used is more than equivalent. It costs. In addition, there is a problem that a large amount of by-products generated from the dehydrating agent used after the reaction needs to be removed by a post-treatment.

[0004]

Means for Solving the Problems In order to solve the above problems, the present inventors have intensively studied a method for dehydrating phthalic acids. It has been found that the reaction proceeds at a high yield by using a drying agent such as molecular sieves or a desired phthalic anhydride, thereby completing the present invention.

The present invention provides a compound represented by the general formula (II):

Embedded image (Wherein R may be the same or different, and represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a C ₁ -C ₂₀ alkyl group,
Halo C ₁ -C ₈ alkyl group, C ₁ -C ₂₀ alkoxy group, halo C _1-
C ₈ alkoxy group, C ₁ -C ₂₀ alkylthio group, halo C ₁ -C ₈ alkylthio group, phenyl group or may be the same or different, halogen atom, C ₁ -C ₆ alkyl group, halo C ₁ -C ₆ alkyl A substituted phenyl group having one or more substituents selected from a group or a C ₁ -C ₆ alkoxy group, and n represents an integer of 0-4. R together with adjacent carbon atoms
It can also represent a C ₄ alkenylene group or a C ₁ -C ₂ alkylenedioxy group. A) a phthalic acid represented by the general formula (I), wherein the phthalic acid is dehydrated in an inert solvent in the presence of a catalytic amount of an acidic compound;

Embedded image (Wherein, R and n are the same as described above). The production method of the present invention is simple in process, efficient, and under mild conditions,
It is another object of the present invention to provide a production method that can produce phthalic anhydrides at low cost and can easily carry out post-treatment.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION In the definition of phthalic acids and phthalic anhydrides of the present invention, "halogen atom" means chlorine atom,
Indicates bromine atom, iodine atom or fluorine atom, the "C ₁ -C ₂₀ alkyl group" such as methyl group, ethyl group, n- propyl group, i- propyl, n- butyl group, i- butyl group, s-butyl group, t-butyl group, n-pentyl group, n
-Hexyl group, n-octyl group, n-dodecyl group, n-
Straight or branched chain carbon atoms such as an eicosyl group
Represents 0 alkyl groups, and “halo C ₁ -C ₈ alkyl group” refers to a straight or branched C _1-8 alkyl group substituted by one or more halogen atoms which may be the same or different. Represents an alkyl group of, for example, fluoromethyl group, difluoromethyl group, trifluoromethyl group, chloromethyl group,
A bromomethyl group, a pentafluoroethyl group, a tetrafluoroethyl group and the like can be mentioned.

The phthalic anhydrides of the general formula (I) of the present invention can be obtained by dehydrating the phthalic acids of the general formula (II) in the presence of an inert solvent in the presence of a catalytic amount of an acidic compound. It can be produced by reacting. Examples of the acidic compound include sulfuric acid, polyphosphoric acid, benzenesulfonic acid,
Acids such as p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, and cation exchange resin can be used.Preferably, sulfonic acids such as benzenesulfonic acid, paratoluenesulfonic acid, and methanesulfonic acid are used. These acidic compounds may be used alone or in combination of two or more.

The amount of the acidic compound used may be a catalytic amount, for example, from 1/2 to 1 /
It may be used within the range of 10000, preferably 1/10 to 1 /
Can be used in the range of 1000. In this reaction, it is necessary to remove water generated during the reaction, and as a removing method, a method using a drying agent such as azeotropic dehydration or molecular sieves can be used. As a desiccant, for example, calcium chloride, calcium oxide,
Examples thereof include magnesium sulfate, silica gel, alumina, and concentrated sulfuric acid.

The inert solvent for this reaction is not particularly limited as long as it does not inhibit this reaction. Examples thereof include aromatic solvents such as toluene and chlorobenzene, halogenated hydrocarbon solvents such as chloroform, and ethers such as dioxane. System solvent,
An inert solvent such as a nitrile solvent such as acetonitrile can be used, and these solvents can be used alone or in combination of two or more. The reaction may be performed at a temperature within the boiling range of the solvent, but is preferably in the range of 50 to 150 ° C.

[0010]

EXAMPLES The present invention will be described in detail below with reference to typical examples, but the present invention is not limited to these examples. (Production Example 1) Toluene 25 m in a 50 ml glass reactor
1, 5 g (30 mmol) of phthalic acid and 0.2 g of paratoluenesulfonic acid monohydrate were added, and the mixture was refluxed for 5 hours while stirring. At this time, the reflux liquid was 5 g of molecular sieves 4
The solution was returned to the reaction system through a drying tube filled with A and continuously dehydrated. After completion of the reaction, insolubles were filtered off and the solvent was distilled off under reduced pressure to obtain 4.2 g of phthalic anhydride. 95% yield

(Production Examples 2 and 3) In the same manner as in Production Example 1, the reaction was carried out by changing the phthalic acid as the starting compound. (Production Examples 4 and 5) The reaction was carried out in the same manner as in Production Example 1 except that the catalyst was changed to trifluoromethanesulfonic acid. (Production Examples 6 to 9) The reaction was carried out in the same manner as in Production Example 1 except that the catalyst was changed. (Production Examples 10 to 11) The reaction was carried out in the same manner as in Production Example 1 except that the solvent was changed. Indicated. (Comparative Example) The reaction was carried out in the same manner as in Example 1 except that no catalyst (acid compound) was used.

The production conditions and results of Production Examples 2 to 11 and Comparative Example are shown in Table 1. In the table, "catalyst (wt%)"
Indicates that the catalyst addition amount is% by weight, and "TsO
"H" stands for paratoluenesulfonic acid and "Toluene"
Means toluene, "Dioxane" means dioxane,
"PPA" indicates polyphosphoric acid, "MCB" indicates monochlorobenzene, and "MS-4A" indicates that molecular sieves 4A is used as a dehydrating agent.

Table 1 Preparation Example Phthalic acid Catalyst (wt%) Solvent Dehydration method Yield (%) ──────────────────────────────── 2 4- (CH ₃ ) C ₆ H ₃ (COOH ) ₂ TsOH (2) Toluene MS-4A 95 3 3- (I) C ₆ H ₃ (COOH) ₂ TsOH (2) Toluene MS-4A 92 4 4,5- (Cl) ₂ C ₆ H ₂ (COOH) ₂ CF ₃ SO ₃ H (2) Toluene MS-4A 80 5 3- (NO ₂ ) C ₆ H ₃ (COOH) ₂ CF ₃ SO ₃ H (2) Toluene MS-4A 25 6 3- (I) C ₆ H ₃ (COOH) ₂ PPA (2) Toluene MS-4A 26 7 3- (I) C ₆ H ₃ (COOH) ₂ H ₂ SO ₄ (2) Toluene MS-4A 54 8 3- (I) C ₆ H ₃ (COOH) ₂ CH ₃ SO ₃ H (2) Toluene MS-4A 92 9 3- (I) C ₆ H ₃ (COOH) ₂ TsOH (2) CH ₃ CN MS-4A 32 10 3- (I) C ₆ H ₃ (COOH) ₂ TsOH (2) Dioxane MS-4A 43 11 3- (I) C ₆ H ₃ (COOH) ₂ TsOH (2) MCB MS-4A 91 Comparative Example 3- (I) C ₆ H ₃ (COOH) ₂ − Toluene MS-4A 7 ────────────────────────────────

Table 2 shows the physical properties of the compounds obtained by the above production methods. Table 2 Physical Properties Example No. ¹ H-NMR δ value (ppm); Solvent Melting point mp (℃) ────────────────────────────────2 2.57 (s, 3H) 7.69 (d, 1H) 7.79 (s, 1H) 7.88 (d, 1H); CDCl ₃ mp 85-86 ℃ 3 7.66 (t, 1H) 8.06 (d, 1H) 8.38 (d, 1H); DMSO-d ₆ mp 163-164 ℃ 4 8.10 ppm (s): CDCl ₃ mp 183-184 ℃ ────────────────────────────────

(Production Example 15) Dean-Stark (Dean-S)
25 ml of chlorobenzene, 5 g (17 mmol) of 3-iodophthalic acid and 0.05 g of p-toluenesulfonic acid monohydrate were added to a 50 ml glass reactor equipped with a tark tube, and the mixture was refluxed with stirring for 5 hours. After completion of the reaction, insolubles were filtered off and the solvent was distilled off under reduced pressure to obtain 4.5 g of anhydrous 3
-Iodophthalic acid was obtained. 96% yield

[0016]

The production method of the present invention is a production method which is simple in terms of process, is efficient, can produce phthalic anhydrides under mild conditions and at low cost, and is simple in post-treatment.

Claims (5)

[Claims] 1. A compound of the general formula (II): (Wherein R may be the same or different, and represents a hydrogen atom, a halogen atom, a nitro group, a cyano group, a C ₁ -C ₂₀ alkyl group,
Halo C ₁ -C ₈ alkyl group, C ₁ -C ₂₀ alkoxy group, halo C _1-
C ₈ alkoxy group, C ₁ -C ₂₀ alkylthio group, halo C ₁ -C ₈ alkylthio group, phenyl group or may be the same or different, halogen atom, C ₁ -C ₆ alkyl group, halo C ₁ -C ₆ alkyl A substituted phenyl group having one or more substituents selected from a group or a C ₁ -C ₆ alkoxy group, and n represents an integer of 0-4. R together with adjacent carbon atoms
It can also represent a C ₄ alkenylene group or a C ₁ -C ₂ alkylenedioxy group. Wherein the phthalic acid represented by the general formula (I) is dehydrated in an inert solvent in the presence of a catalytic amount of an acidic compound; (Wherein, R and n are the same as described above). 2. The method according to claim 1, wherein the acidic compound is a sulfonic acid. 3. The method according to claim 2, wherein the sulfonic acid is paratoluenesulfonic acid. 4. The method according to claim 1, wherein the dehydration reaction is an azeotropic dehydration reaction.
The method according to any one of claims 1 to 3. 5. The production method according to claim 1, wherein the dehydration reaction is a dehydration reaction using a desiccant.