JPH05238987A - Production of aromatic carboxylic acid chloride - Google Patents

Abstract

PURPOSE:To obtain the subject high-purity compound in high selectivity, in high yield and inexpensively without using a catalyst by distilling away an aromatic carboxylic acid chloride from a reaction mixture to give residue and using the residue together with an aromatic carboxylic acid and SOCl2 for the following reaction. CONSTITUTION:First, an aromatic carboxylic acid of the formula (R is H or 1-6C alkyl; (m) is 1-5; (n) is 0-4; with the proviso that m+n=5) is allowed to react with thionyl chloride, SOCl2, preferably at 50-150 deg.C the reaction mixture is distilled and the formed objective compound is separated. Then, the residue after the distillation containing an aromatic carboxylic acid anhydride as a byproduct is reacted with the aromatic carboxylic acid as a raw material and thionyl chloride. Further, these operations are repeated to give the objective compound. Pentafluorobenzoic acid or 2,4-difluorobenzoic acid are preferable as the raw material compound of the formula. For example, toluene, p-xylene, etc., may be cited as an inert solvent used for the reaction.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to aromatic carboxylic acid chloride, particularly pentafluorobenzoic acid chloride (hereinafter referred to as PFBC) useful as an intermediate for pharmaceuticals and photosensitive materials, and pentafluorobenzoic acid (hereinafter referred to as PFBA). )) And thionyl chloride.

[0002]

2. Description of the Related Art A method for synthesizing PFBC from PFBA and thionyl chloride is described in Journal of Organic Chemistry (J. Org. Chem.) Vol. 35, No. 4 p930.
~ 5, 1970. However, only the method for synthesizing PFBC is disclosed, and no examination from an industrial viewpoint such as effective use of by-products is described. Further, in the disclosed method, the reaction time is as long as 16 hours, and the obtained PFBC is colored in pale yellow, so that the purity is low and the distillation yield is 81%.

In addition to the above, Journal of Chemical Society (J. Chem. Soc.) No. 15, p1933
During the EXPERIMENTAL of ~ 7,1968, PFBA
And PFBC synthesis method from phosphorus pentachloride are described, but phosphorus pentachloride is expensive and has a problem of treating phosphorus waste, and both raw materials are solid, so that there is a problem in operability. However, since a large amount of inorganic salt is produced as a by-product, it is not sufficient as an industrial production method because it is expensive.

[0004]

[Problems to be Solved by the Invention]
When it comes to a method for manufacturing an FBC, a sufficient process has not yet been developed in the conventional technology. Furthermore, this synthetic reaction has some problems described below.

For example, the raw material PFBA is expensive, and the use of a large amount of thionyl chloride in order to improve the yield of PFBC is uneconomical and has a safety problem.

In addition, increasing the yield by using a catalyst is
There is a problem of by-products, and it needs to be done carefully. This is because the carboxyl group of PFBA is less reactive than other aliphatic carboxyl groups, while the fluorine atom of the aromatic ring is highly reactive. Therefore, there is a concern that various side reactions may occur due to the action of the catalyst or the like.

In particular, from PFBA and thionyl chloride to PFB
When synthesizing C, it is desirable to avoid the use of a catalyst as much as possible. The reason is that various side reactions may be induced during the reaction and during the distillation separation due to high temperature. Increasing the degree of vacuum for distillation at a lower temperature leads to higher equipment costs. In addition, since this reaction handles a large amount of corrosive substances, using a large amount of equipment made of expensive materials that can withstand corrosion will also lead to soaring equipment costs.

It is desirable that the PFBC has a high purity from the use, and it may not be suitable for the use at all depending on the structures of by-products and impurities.

Further, in the reaction between PFBA and thionyl chloride, pentafluorobenzoic acid anhydride (hereinafter referred to as F5 acid anhydride) is by-produced regardless of the presence or absence of a catalyst. If the F5 acid anhydride produced as a by-product is discarded, the raw material cost becomes high, and the disposal method is not simple, so that the processing method becomes a problem in the industrial manufacturing method.

As described above, the synthesis of PFBC from PFBA and thionyl chloride has conditions that are very restricted by the reactivity of PFBA and the use of PFBC. The object of the present invention is to provide P under these special conditions.
An object of the present invention is to provide a method for industrially producing an aromatic carboxylic acid chloride containing FBC with high purity at low cost and in high yield.

[0011]

For example, the reaction between pentafluorobenzoic acid and thionyl chloride proceeds according to formula (I),

[0012]

[Chemical 2]

At the same time, pentafluorobenzoic anhydride is produced as a by-product according to the formula (II).

[0014]

[Chemical 3]

Therefore, in the present invention, in the method for producing an aromatic carboxylic acid chloride in which an aromatic carboxylic acid represented by pentafluorobenzoic acid is reacted with thionyl chloride, the reaction product is distilled to obtain the aromatic carboxylic acid chloride. Along with obtaining the same, the residue containing the by-produced aromatic carboxylic acid anhydride after distillation is industrially produced at high yield and high purity at low cost by subjecting the residue containing the by-produced aromatic carboxylic acid anhydride to the next reaction together with the aromatic carboxylic acid. I found what I could do.

That is, in the method for producing pentafluorobenzoic acid chloride in which pentafluorobenzoic acid and thionyl chloride are reacted, it is considered that the F5 acid anhydride produced as a by-product becomes PFBC which is the target product according to the following formula (III). ..

[0017]

[Chemical 4]

As a result, the yield of PFBC from PFBA is improved.

The above-mentioned aromatic carboxylic acids include pentafluorobenzoic acid, 2,3,4,5-tetrafluorobenzoic acid, 2,
3,5,6-tetrafluorobenzoic acid, 2,3,4-trifluorobenzoic acid, 2,3,5-trifluorobenzoic acid, 2,4-difluorobenzoic acid, 4-monofluorobenzoic acid, 2- Methyl-4-fluorobenzoic acid, 2,4-dimethyl-6-fluorobenzoic acid, 2,
6-dimethyl-4-fluorobenzoic acid and the like can be mentioned, but among them, pentafluorobenzoic acid, 2,3,4,5-tetrafluorobenzoic acid, 2,4-difluorobenzoic acid, 2-methyl-4-fluorobenzoic acid. The acid, 2,4-dimethyl-6-fluorobenzoic acid, is preferred.

Next, regarding the production method, the case of producing PFBC from PFBA and thionyl chloride is taken as an example, and FIG.
Will be described in detail with reference to.

The definitions of conversion rate, selectivity and yield are as follows. Conversion (mol%) = (consumed PFBA (mol) / charged P
FBA (mol)) × 100 Selectivity (mol%) = (PFBC (mol) formed / P consumed
FBA (mol)) × 100 Yield (mol%) = (PFBC (mol) formed / PFB charged)
A (mol)) × 100 First, charge PFBA and thionyl chloride into the reactor (S1
And S2). All the raw materials may be charged all at once, or a part of the raw materials may be dividedly charged. The amount of thionyl chloride used is not particularly limited, but a range of 0.5 to 10 mol of thionyl chloride, preferably 1.0 to 4.0 mol is suitable for 1 mol of PFBA. In the reaction, a solvent inert to thionyl chloride and PFBA may be used.
Although the reaction temperature depends on the composition of the charged materials, that is, the ratio of raw materials and the presence or absence of a solvent, 40 to 200 ° C is suitable, and more preferably 50 to 150 ° C. The appropriate reaction time also depends on the composition of the feed, the form of the reaction, and the reaction temperature. Although the reaction rate becomes slower near the end of the reaction, it may be possible to move to the step of distilling the next PFBC when PFBA of several% of the charged amount remains. This is because the reaction proceeds even during the distillation process, and the conversion of PFBA approaches 100% or becomes 100% (S
3). Further, even if PFBA remains in the bottom after the end of distillation, it does not have any bad influence on the repeated reaction. Following the reaction step, the distillation step may be carried out in the same vessel as the one in which the reaction was performed, or may be transferred to another vessel for distillation.

In the distillation step, the unreacted remaining thionyl chloride is first distilled off, and then the product PFBC is distilled off.
The distilled thionyl chloride and the mixture of thionyl chloride and PFBC, which cannot be used as a product, are advantageous in terms of production cost when reused for subsequent reactions and distillations (S4). The distillation of PFBC may be carried out at normal pressure,
It may also be carried out under reduced pressure. When the distillation of PFBC is completed, the F5 acid anhydride remains at the bottom (S6). At this time, a part of PFBC remains together with the F5 acid anhydride, but its composition varies depending on the distillation conditions. In this production method, PFBA as a raw material and thionyl chloride (S1) are newly added to the distillation residue in which the F5 acid anhydride is present, and the following reaction is carried out. That is, the process surrounded by the alternate long and short dash line in FIG. 1 is repeated to obtain the product PFBC. At this time, about 20 times is suitable industrially, but it is possible to repeat more times and there is no limitation.

When repeating the reaction, the composition before the reaction, that is, (newly added raw material (PFBA, thionyl chloride)) / (distillation residue of the previous reaction (F5 acid anhydride, PF)
BC)), the ratio of PFB in repeated reactions
The conversion of A and the selectivity of PFBC will vary. P
In the reaction of FBA and thionyl chloride, the conversion of PFBA and the selectivity of PFBC differ depending on the conditions during the reaction.
In this manufacturing method, the conversion rate is almost 100%, and the PFBC
Also has a selectivity of 70 to 100%. PFBA during the reaction
It is presumed that F5 acid anhydride is produced from PFBC and PFBC, or PFBC is produced from F5 acid anhydride and thionyl chloride. Apparently, PFBA is produced from PFBA and thionyl chloride.
There is a point that the reaction with the conversion of 100% and the selectivity of PFBC of 100% is proceeding. That is, the amount of F5 acid anhydride does not change before and after the steps from the reaction to the distillation, and the reaction conditions (the steps of raw material charging, reaction, and distillation) are in a steady state (reaction conditions before the reaction). Composition, ratio of raw material to bottom, reaction temperature, reaction form, etc.). The steady state and the reaction conditions mentioned here are related to each other. For example, if the raw material composition before the reaction changes, then in the steady state, the newly added raw material (PFBA, thionyl chloride) and the distillation residue of the previous reaction (F5 acid anhydride The ratio of goods, PFBC) will also change. Therefore, if the steady state shifts, PFBA
The selectivity of PFBC calculated from the conversion of PFBC may exceed 100% in some cases because the production of PFBC occurs from F5 acid anhydride and thionyl chloride.

When the above reaction is completed, water is added to the residue after distillation for hydrolysis, and then the residue is discarded (S7).
And S8).

As the inert solvent used in the above reaction, aromatic hydrocarbons such as toluene, p-xylene, m-xylene, o-xylene and dodecylbenzene, and fats such as n-decane and n-dodecane are used. Group hydrocarbons are mentioned.

Hereinafter, the embodiments of the present invention will be specifically shown by examples, but the present invention is not limited thereto. That is, the reaction composition, reaction temperature, reaction time, distillation conditions and other conditions are not limited to the examples.

[0027]

【Example】

[Example 1] 689 g (3.25 mol) of PFBA and 464 g (3.90 mol) of thionyl chloride were mixed, and the mixture was heated under stirring and reacted under reflux for 6 hours. Conversion rate of PFBA 10
The selectivity was 0% and the PFBC selectivity was 65%. After aging, PFBC was separated by distillation. In the distillation, excess thionyl chloride was first distilled off, and then PFBC was distilled off under reduced pressure. 420g PFBC with 99% purity and almost no color
(Isolated yield 56%) was obtained, and after distillation, a mixture of 229 g of F5 acid anhydride and 57 g of PFBC remained in the bottom.

Example 2 After distillation in Example 1, 517 g (2.44 g) of PFBA was newly added to the bottom containing the residue.
Mol) and 348 g (2.92 mol) of thionyl chloride were added. The mixture at this point is in a slurry state,
In the same manner as above, the temperature was raised under stirring to react. As a result of the analysis, the conversion rate of PFBA is 100%, and the yield of PFBC is 70%.
Met. After this, 350 g of PFBC with a purity of 99% and almost no coloration (isolation yield 62%) were obtained by distillation, and 375 g of F5 acid anhydride and PFBC were obtained in the bottom after distillation.
94 g of the mixture remained. Combining the first time (Example 1) and the second time (Example 2), PFBA used as a raw material
The amount of PFBC produced was 881 g (3.82 mol, yield 67%) per 1206 g (5.69 mol), and the isolated yield after distillation was 770 g (3.34 mol, isolated yield 59%). Met.

[Example 3] After distillation in Example 2, 407 g (1.92 PFBA) of PFBA was newly added to the bottom containing the residue.
Mol) and thionyl chloride 274 g (2.30 mol),
The reaction was carried out in the same manner as in Example 2. As a result of analysis, PFB
The conversion rate of A was 100% and the yield of PFBC was 81%.
Then, by distillation, P with a purity of 99% and almost no color
337 g of FBC (76% isolated yield) was obtained, and after distillation, a mixture of 447 g of F5 acid anhydride and 112 g of PFBC remained in the bottom. Combining the first time (Example 1) to the third time (Example 3), PFBA16 used as a raw material
The PFBC produced was 12 per 13 g (7.61 mol).
It was 39 g (5.37 mol, yield 71%), and the isolated yield after distillation was 1107 g (4.80 mol, isolated yield 63%).

Example 4 After the distillation in Example 3, 355 g (1.67 PFBA) of PFBA was newly added to the bottom containing the residue.
Mol) and thionyl chloride 240 g (2.02 mol),
The reaction was carried out in the same manner as in Example 2. As a result of analysis, PFB
The conversion rate of A was 99% and the yield of PFBC was 94%. Then, by distillation, PF with a purity of 99% and almost no color
BC357g (isolation yield 93%) was obtained, and after distillation, a mixture of F5 acid anhydride 465g and PFBC116g remained at the bottom. Combining the first time (Example 1) to the fourth time (Example 4), PFBA19 used as a raw material
The PFBC produced per 68 g (9.28 mol) was 16
The amount was 01 g (6.95 mol, yield 75%), and the isolated yield after distillation was 1464 g (6.35 mol, isolated yield 68%).

[Example 5] After distillation in Example 4, 338 g (1.59 PFBA) of PFBA was newly added to the bottom containing the residue.
Mol) and 231 g (1.94 mol) of thionyl chloride,
The reaction was carried out in the same manner as in Example 2. As a result of analysis, PFB
The conversion of A was 98% and the yield of PFBC was 101%.
Then, by distillation, P with a purity of 99% and almost no color
370 g of FBC (isolation yield 101%) was obtained, and after distillation, a mixture of 460 g of F5 acid anhydride and 115 g of PFBC remained at the bottom. Summarizing the first time (Example 1) to the fifth time (Example 5), PFBA2 used as a raw material
The amount of PFBC produced relative to 306 g (10.87 mol) was 1971 g (8.55 mol, yield 79%), and the isolated yield after distillation was 1834 g (7.96 mol, isolated yield 73).
%)Met.

Example 6 Continuous operation was performed below.
The performance during steady operation is 100% PFBA conversion and PF
The yield of BC was 100%.

The following Examples 7 and 8 are examples in which 2,3,4,5-tetrafluorobenzoic acid chloride (hereinafter referred to as TFBC) was produced as the aromatic carboxylic acid chloride. The definitions of the conversion rate, the selectivity and the yield in each example are the same as in the case of PFBC.

Example 7 424 g of 2,3,4,5-tetrafluorobenzoic anhydride (hereinafter referred to as F4 acid anhydride)
(1.15 mol) and 107 g (0.50 mol) of TFBC were added to a mixture of 2,3,4,5-tetrafluorobenzoic acid (hereinafter referred to as TF).
309 g (1.59 mol) of BA) and 231 g (1.94 mol) of thionyl chloride were added and the reaction was carried out in the same manner as in Example 5.

As a result of the analysis, the conversion rate of TFBA was 100%,
The yield of TFBC was 102%. After this, distillation yielded TFBC 346 g (isolated yield 102%) with 99% purity and almost no coloration, leaving a mixture of F4 acid anhydride 416 g and TFBC 104 g in the bottom after distillation.

[Embodiment 8] Hereinafter, continuous operation was performed in the same manner as in Embodiment 6. The performance during steady operation was 100% TFBA conversion and 100% TFBC yield.

[0037]

EFFECTS OF THE INVENTION According to the method for producing an aromatic carboxylic acid chloride of the present invention, a highly pure aromatic carboxylic acid chloride can be obtained with a high selectivity and a high yield without using any catalyst. Has the effect.

[Brief description of drawings]

FIG. 1 is an explanatory view showing a manufacturing process of the present invention.

Claims (1)

[Claims] 1. A general formula: (In the formula, R represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, F represents fluorine, and R may be the same or different. M + n = 5, m is an integer of 1 to 5, n
Is an integer of 0 to 4), and a method for producing an aromatic carboxylic acid chloride from an aromatic carboxylic acid represented by the formula and thionyl chloride, 1) after the reaction, the aromatic carboxylic acid chloride is separated by distillation, 2) A method for producing an aromatic carboxylic acid chloride in which the steps of 1) and 2) in which a raw material aromatic carboxylic acid and thionyl chloride are charged to a residue containing a by-produced aromatic carboxylic acid anhydride after distillation and the reaction is repeated.