JPH0239493B2 - HOKOZOKUKAGOBUTSUNOSEIZOHOHO - Google Patents

Description

[Detailed description of the invention]

The present invention provides a method for producing an aromatic compound having both a trifluoromethyl group and an aldehyde group, which serves as an intermediate raw material for producing various useful compounds. More specifically, at least one of the hydrogen atoms bonded to the basic skeleton of the aromatic compound is a trifluoromethyl group, and at least one of the other hydrogen atoms is a trifluoromethyl group.
However, an aromatic compound substituted with a dihalomethyl group represented by the general formula -CHXY (where X and Y are the same or different halogen atoms),
In the presence of sulfuric acid with a concentration of 80% or more and with a short reaction time.
Within 60 minutes, or the sulfuric acid concentration (C weight %) and reaction time (t minutes) are expressed by the formulas (A); C = 178/t + 8 + 81 and (B); C450/t + 79 (however, 80≦C≦86.5, 60≦ The present invention relates to a method for producing an aromatic compound having a trifluoromethyl group and an aldehyde group, which is characterized in that the aromatic compound is hydrolyzed under conditions shown by t≦100. Conventionally, aromatic compounds having both a trifluoromethyl group and an aldehyde group, such as trifluoromethylbenzaldehyde and trifluoromethylnaphthaldehyde, have been known as intermediate raw materials for producing various useful substances such as pharmaceuticals, agricultural chemicals, dyes, and other chemicals. It is a compound. However, these manufacturing methods have low yields based on the raw materials, and the compounds are generally expensive because they are manufactured through complicated manufacturing steps. For example, Analytical chimica actor (Analytical chimica actor)
Acta) 10 43 (1956), when o-trifluoromethylbenzal chloride is hydrolyzed at 100°C for 2 hours in the presence of a 3:1 mixture of concentrated sulfuric acid and water, o-trifluoromethylbenzaldehyde is produced. It has been shown that a yield of 44% relative to the raw material can be obtained. The inventors of the present invention tried the above method again, and as a result, o-trifluoromethylbenzaldehyde was obtained with almost the same yield, and the method could not be said to be industrially satisfactory. A large amount of tar-like material was produced in the reaction system, and in this sense, the above method could not be considered as an industrial production method. On the other hand, o-trifluoromethylbenzaldehyde was obtained in 95% yield by treating o-trifluoromethylbenzalfluoride in the presence of 95% sulfuric acid at 90-120°C for 2-3 hours. There are also reports. Based on the above report, the present inventors repeatedly conducted follow-up tests under the above conditions, but were unable to prevent the formation of tar-like substances in the reaction system, and the yield was over 50%.
It was not possible to obtain trifluoromethylbenzaldehyde. On the other hand, from an industrial standpoint, raw materials such as trifluoromethylbenzalfluoride are generally obtained by fluorinating a chlorine compound corresponding to the raw aromatic compound of the present invention as its precursor compound. In this case, the CCl ₃ groups in the precursor compound are completely converted to CF ₃ groups, but the CHCl ₂ groups are not susceptible to the fluorination reaction and may remain unreacted or
In most cases, the resulting reaction product is a mixture of various compounds, as the reaction may stop at conversion to CHClF groups or proceed to _two CHF groups. Isolating specific compounds from these mixtures not only increases production costs from an industrial perspective, but also requires complicated equipment for isolation of some compounds. Therefore, it was necessary to develop a technique that uses the above-mentioned mixture as much as possible to obtain a single target product through the same treatment. However, such a technique has not yet been proposed. Based on this background, the present inventors have endeavored to develop a technique for obtaining a single target product at once from a mixture of various raw materials. As a result, an aromatic compound in which at least one of the hydrogen atoms bonded to the basic skeleton of the aromatic compound was substituted with a trifluoromethyl group and at least one of the other hydrogen atoms was substituted with a dihalomethyl group was prepared in the presence of sulfuric acid. In the hydrolysis reaction to form aromatic compounds having trifluoromethyl groups and aldehyde groups, sulfuric acid concentration and reaction time have important effects, and by combining specific conditions of the two, tar It has been found that not only can the formation of such substances be almost completely prevented, but also that a single target product can be produced in high yield even when the raw materials are the above-mentioned mixtures. Based on this knowledge, we have completed the present invention through repeated statistical experiments and have come to propose it here. That is, the present invention provides that at least one of the hydrogen atoms bonded to the basic skeleton of the aromatic compound is a trifluoromethyl group, and that at least one of the hydrogen atoms has the general formula -CHXY (provided that X and Y are of the same type). or a different type of halogen atom) at a concentration of 80
% or more of sulfuric acid and the reaction time is within 60 minutes, or sulfuric acid concentration (C weight %) and reaction time (t minutes)
is hydrolyzed between the conditions shown by the formulas (A); C = 178 / t + 8 + 81 and (B); C = 450 / t + 79 (however, 80≦C≦86.5, 60≦t≦100) This is a method for producing an aromatic compound having a trifluoromethyl group and an aldehyde group. The basic skeleton of the aromatic compound as a raw material used in the present invention is aromatic hydrocarbons such as benzene, naphthalene, and anthracene, but pyridine,
Aromatic compounds such as quinoline can also be used without particular limitation. What is important about the raw materials used in the present invention is that at least one of the hydrogen atoms bonded to the basic skeleton of the aromatic compound is a trifluoromethyl group, and at least one of the other hydrogen atoms has the general formula, -CHXY ( provided that X and Y are each substituted with a dihalomethyl group represented by (X and Y are the same or different halogen atoms). That is, at least one of the hydrogen atoms bonded to the basic skeleton is a trifluoromethyl group (-CF ₃ ) or a dihalomethyl group (-
If it is an aromatic compound substituted with CHXY),
The remaining hydrogen atoms may be substituted with other functional groups such as halogen atoms. In addition, the dihalomethyl group mentioned above is a dichloromethyl group (-CHCl ₃ ), a chlorofluoromethyl group (-CHClF), and a difluoromethyl group (-CHF ² ), which are commonly used in the production of raw materials used in the present invention. The atom is not particularly limited, even if it is a bromine atom or an iodine atom. In addition, the number of hydrogen atoms bonded to the basic skeleton of the aromatic compound to be substituted with trifluoromethyl groups and dihalomethyl groups is at least 1 for each of these groups.
The maximum number of substitutions is the same as the number of hydrogen atoms. As described above, the dihalomethyl group may also have a plurality of groups containing the same or different halogen atoms bonded to each other. The aromatic compound as a raw material that can be used in the present invention may be an aromatic compound having the above-mentioned trifluoromethyl group (-CF ₃ ) and dihalomethyl group [-CHXY (however, X and Y are the same or different halogen atoms)]. Although they can be used without any particular limitation, the following are specific examples of those that are generally suitably used. For example, 1-trifluoromethyl-2-dihalomethylbenzene, 1-trifluoromethyl-3-
Dihalomethylbenzene, 1-trifluoromethyl-4-dihalomethylbenzene, 3-dihalomethyl-4-trifluoromethylhalobenzene, 2-trifluoromethyl-3-dihalomethylhalobenzene, 3-trifluoromethyl- 4-dihalomethylhalobenzene, 2-trifluoromethyl-6-dihalomethylhalobenzene, 2-dihalomethyl-4
-trifluoromethylhalobenzene, 3-trifluoromethyl-5-dihalomethylhalobenzene,
2-trifluoromethyl-4-dihalomethylhalobenzene, 2-trifluoromethyl-5-dihalomethylhalobenzene, 2-dihalomethyl-5-trifluoromethylhalobenzene, 1,2-bis(trifluoromethyl) -4-dihalomethylbenzene, 1,4-bis(trifluoromethyl)-2
-dihalomethylbenzene, 1,3-bis(trifluoromethyl)-5-dihalomethylbenzene,
1,3-bis(dihalomethyl)-4-trifluoromethylbenzene, 1,2-bis(dihalomethyl)-4-trifluoromethylbenzene, 1,3
-Bis(dihalomethyl)-5-trifluoromethylbenzene, 1,3-bis(dihalomethyl)-2
-trifluoromethylbenzene, 1,4-bis(trifluoromethyl)-2,5-bis(dihalomethyl)benzene, 1,5-bis(trifluoromethyl)-2,4-bis(dihalomethyl)benzene, 1, 3,4-tris(dihalomethyl)-6-
Trifluoromethylbenzene, 1-trifluoromethyl-3-dihalomethylnaphthalene, 1-dihalomethyl-3-trifluoromethylnaphthalene,
1-trifluoromethyl-2-dihalomethylnaphthalene, 1-dihalomethyl-2-trifluoromethylnaphthalene, 1-trifluoromethyl-4-
Dihalomethylnaphthalene, 1-trifluoromethyl-5-dihalomethylnaphthalene, 2-trifluoromethyl-3-dihalomethylnaphthalene, 2-
Trifluoromethyl-6-dihalomethylnaphthalene, 2,5-bis(trifluoromethyl)-3-
Dihalomethylnaphthalene, 2,8-bis(trifluoromethyl)-3-dihalomethylnaphthalene,
2,5-bis(dihalomethyl)-3-trifluoromethylnaphthalene, 2,8-bis(dihalomethyl)-3-trifluoromethylnaphthalene, 1,
3-bis(dihalomethyl)-5-trifluoromethylnaphthalene, 9-trifluoromethyl-10-
Dihalomethylanthracene, 9-dihalomethyl-
10-trifluoromethylanthracene, 2-trifluoromethyl-3-dihalomethylpyridine, 2
-dihalomethyl-3-halo-5-trifluoromethylpyridine, 2-dihalomethyl-3-trifluoromethylpyridine, 2-dihalomethyl-4-trifluoromethylpyridine, 2-trifluoromethyl-4-dihalomethylpyridine, 2 -trifluoromethyl-5-dihalomethylpyridine, 2-dihalomethyl-5-trifluoromethylpyridine,
2-trifluoromethyl-6-dihalomethylpyridine, 3-dihalomethyl-4-trifluoromethylpyridine, 3-trifluoromethyl-4-dihalomethylpyridine, 3-trifluoromethyl-5
-dihalomethylpyridine, 2-trifluoromethyl-4-dihalomethylquinoline, 2-dihalomethyl-4-trifluoromethylquinoline, 2-trifluoromethyl-6-dihalomethylquinoline, 2
-dihalomethyl-6-trifluoromethylquinoline, etc. Among these compounds, compounds represented by the following general formula are particularly preferably used because their raw materials are easily available and are widely used as various intermediates. That is, the general formula,

[Formula] (However, Z is a hydrogen atom or a halogen atom, and 2
More than one species of halogen atoms may be bonded, n
is a positive integer from 1 to 5, j, k and l are integers from 0 to 5, m is an integer from 0 to 4, and n+j+k+l+m=
6, 5≧j+k+l≧1. As explained above, a variety of aromatic compounds can be used as raw materials that can be used in the present invention, but in order to simplify the explanation, in the following explanation, trifluoromethylbenzal halide (hereinafter abbreviated as TFMBH) will be used. (There are also examples). For other raw material aromatic compounds, the following TFMBH may be followed. The method for producing TFMBH is not particularly limited, but generally an aromatic compound having multiple methyl groups is treated with Cl ₂ to release at least one -CH ₃ -
A suitable method would be to convert other --CH ₃ to --CHCl ₂ and then fluorinate with anhydrous hydrofluoric acid or the _like to convert --CCl ₃ to --CF ₃ . In the present invention, for example, TFMBF obtained by the above method does not necessarily need to be purified and extracted as a single compound; for example, trifluoromethylbenzal chloride, trifluoromethylbenzalfluoride, trifluoromethylbenzalchlorofluoride, It has the advantage that it can be used as a raw material even if it is a mixture of carbon and the like. From an industrial standpoint, this is an immeasurable advantage as it eliminates the need to separate and purify the raw materials used in the present invention into individual compounds. The greatest feature of the present invention is that the concentration of sulfuric acid used and reaction conditions for hydrolyzing TFMBE are selected specifically. These conditions will be explained in detail below. First, the concentration of sulfuric acid used in the present invention needs to be 80% or more. When using sulfuric acid at a concentration lower than the above, the reaction rate will not only be extremely slow regardless of other conditions, but also the hydrolysis reaction must be carried out with a satisfactory yield even if the reaction is carried out for a long time. I can't get it. Generally, industrially, it is preferable to use sulfuric acid with a concentration of 85% or more. Although the amount of sulfuric acid used is not particularly limited, it is generally preferred to select it so that the sulfuric acid/raw material aromatic compound (molar ratio) is 2 or more. Although it is not clear by what mechanism the sulfuric acid is involved in the hydrolysis reaction of the present invention, the present inventors believe that the dihalomethyl group and sulfuric acid once react to form a sulfuric ester, and that the sulfuric ester is converted into water. It is presumed that the sulfuric acid group reacts with the aldehyde group to generate an aldehyde group, and the sulfuric acid group changes to the original sulfuric acid. The second important requirement in the present invention is that the hydrolysis reaction be carried out within specific conditions in the reaction under the sulfuric acid concentration. The reaction time is 60
If the time is selected within minutes or exceeds 60 minutes, the sulfuric acid concentration (C weight %) and reaction time (t minutes) are calculated using the formula (A);
It is preferable to choose between the following conditions: C=178/t+8+81 and (B); C=450/t+79 (80≦C≦86.5, 60≦t≦100). Under conditions other than these, by-products and tar-like compounds increase significantly, although the reason is still unclear. From this phenomenon, when the reaction time exceeds the above conditions in the presence of 80% or more sulfuric acid, one reason is that even trifluoromethyl groups other than dihalomethyl groups in the raw material compound begin to hydrolyze and are converted to carboxyl groups. Although the formation of the compound and the reaction mechanism are unknown, it is thought that this is because a tar-like compound suddenly begins to be formed. As described above, in the present invention, the concentration of sulfuric acid used and the reaction time play a decisive role in increasing the yield of the target product. Such a phenomenon is completely unexpected, and in particular, the fact that the formation of tar-like substances and the formation of width products can be almost prevented is a great contribution to industrial implementation. Moreover, as mentioned above, as long as the reaction time and sulfuric acid concentration are selected,
Even if the raw material TFMBH is used as a mixture, a single target product, trifluoromethylbenzaldehyde, can be obtained with a yield of 95% or more. This point is also an immeasurable advantage from an industrial perspective. Specific examples of how the sulfuric acid concentration (C weight %) and the reaction temperature (t minutes) affect the present invention will be described in the examples below, but it is important to note that the desired product can be obtained in high yield. Moreover, in order to prevent the formation of tar-like substances, it is most preferable to select the sulfuric acid concentration and reaction time from the conditions shown by the following formulas (A)' and (B)'. However, the following formulas (A)' and (B)' are the above formulas.
Together with (A) and (B), this is an empirical formula determined by the inventors through numerous statistical experiments and analysis of the data. C=178/t+8+81 (A)′ C=450/t+79 (B)′ (However, 80≦C≦100, 0≦t≦100) Above formula (A)′
The relationship between the sulfuric acid concentration and the reaction time, indicated by (B)' and (B)', is as shown in FIG. Further, each plot point shown in FIG. 1 is under the conditions of Examples and Comparative Examples described later, and the numbers in parentheses indicate the yield of the target product. On the other hand, since the reaction temperature is unlikely to be a significant factor in the hydrolysis reaction, it may be appropriately determined as necessary. Generally, the reaction temperature usually adopted is
The temperature range is from 60 to 140°C, preferably from 80 to 130°C. For the hydrolysis reaction in the present invention, both a batch reaction system and a continuous flow reaction system are suitably used, and these can be used in combination as necessary. In the batch method, the reaction time is preferably determined by measuring the time elapsed after mixing the sulfuric acid and the raw aromatic compound, for example, when they are brought into contact with a heating bath at a predetermined temperature; in the continuous flow method, the reaction time is preferably determined by In this case, it is preferable to determine the residence time required for the sulfuric acid and the raw material aromatic compound to pass through the heating reaction layer portion in an extrusion flow. In the case of the above-mentioned hydrolysis reaction, especially in a batch method, it is preferable to sufficiently stir the reaction solution. Further, in order to reduce the influence of moisture and oxygen in the reaction system, it is also a preferable embodiment to carry out the reaction in an atmosphere of an inert gas such as nitrogen gas. In either of the above methods, the liquid after the reaction may be poured into cold water to complete the hydrolysis reaction. The separation and purification method for the produced target compound varies depending on the type of target product, reaction conditions, use of the target compound, etc., and cannot be generalized. For example, the reaction solution is once subjected to steam distillation or directly extracted with an organic solvent (e.g. ether, methylene chloride, etc.), and if necessary, only the aldehyde compound is extracted with an aqueous sodium bisulfite solution, followed by distillation or It can be purified by recrystallization. As explained above, the present invention uses sulfuric acid at a specific concentration and selects specific reaction conditions to produce an aromatic compound containing a trifluoromethyl group and an aldehyde group using an aromatic compound containing a trifluoromethyl group and a dihalomethyl group as a raw material. 70%~95% aromatic compounds
It is possible to obtain higher yields than this range. Further, the target product obtained in the present invention can be purified as necessary to obtain a highly pure product, and can be suitably used as an intermediate raw material for medicines, agricultural chemicals, dyes, and other chemicals, either as is or after being purified. Furthermore, since the reaction of the present invention usually involves the generation of corrosive gases such as HF and HCl, the material for the inner wall of the reactor is a synthetic resin that is stable at the reaction temperature, such as a fluorine-based resin such as polypropylene and polytetrafluoroethylene; It may be appropriately selected from metals or alloys such as nickel and monel. EXAMPLES In order to illustrate the present invention more specifically, the present invention will be described below with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples. Example 1 10 g o-trifluoromethylbenzal chloride
and 30 g of 87% sulfuric acid (sulfuric acid/trifluoromethylbenzal chloride (molar ratio) = 6.1) were placed in a 100 ml Teflon flask equipped with a stirrer, and the flask was immersed in an oil bath at a temperature of 100°C. Stirring was started. After 2 to 3 minutes, hydrogen chloride gas began to be generated vigorously. After about 25 minutes of reaction time, the flask was taken out of the oil bath and the liquid in the flask was poured into about 200 ml of ice water to terminate the reaction. Next, add 100ml of methylene chloride to the reaction solution.
After extraction twice and drying with magnesium sulfate, o-trifluoromethylbenzaldehyde was distilled under reduced pressure.
7.4 g (yield 97%) was obtained. Example 2 By the same method as in Example 1 using 10 g of 1-trifluoromethyl-2-chlorofluoromethylbenzene and 25 g of 91% sulfuric acid (sulfuric acid/trifluoromethylchlorofluoromethylbenzene (molar ratio) = 4.9). Carry out the hydrolysis reaction at 100 °C for 15 min.
The same post-treatment as in Example 1 was carried out. This result o
-Trifluoromethylbenzaldehyde 8.0g
(yield 98%). Example 3 o-trifluoromethylbenzalfluoride 10
Using g and 30 g of 97% sulfuric acid (sulfuric acid/trifluoromethylbenzal fluoride (molar ratio) = 5.8), a hydrolysis reaction was carried out at 90°C for 20 minutes in the same manner as in Example 1. The same post-processing was performed. As a result, 8.7 g (yield 98%) of o-trifluoromethylbenzaldehyde was obtained. Example 4 o-Trifluoromethylbenzal chloride obtained by fluorinating o-trichloromethylbenzal chloride with hydrogen fluoride, 1-trifluoromethyl-
Molar ratio of 2-chlorofluoromethylbenzene and o-trifluoromethylbenzal fluoride
10g of liquid raw material mixture containing 40:15:45 ratio and 94
% sulfuric acid 30g (sulfuric acid/raw material mixture (mole ratio) = 6.1)
at 120℃ using the same method as in Example 1.
The hydrolysis reaction was carried out for 15 minutes, and the same post-treatment as in Example 1 was carried out. As a result, 8.0 g (yield 97%) of o-trifluoromethylbenzaldehyde was obtained. Example 5 P-trifluoromethylbenzal chloride 10g
A hydrolysis reaction was carried out at 100°C for 55 minutes in the same manner as in Example 1 using Post-processing was performed. As a result, 7.2 g (yield 95%) of P-trifluoromethylbenzaldehyde was obtained. Comparative Example 1 Liquid of exactly the same raw material mixture as used in Example 4
10g and 30g of 95% sulfuric acid (sulfuric acid/raw material (molar ratio) =
6.1), a hydrolysis reaction was carried out in the same manner as in Example 1, except that the reaction temperature was 100°C and the reaction time was 3 hours. The liquid after the reaction is quite viscous.
When poured into 200ml of ice water, it was confirmed that a tar-like compound was generated. This liquid was once extracted three times with 100 ml of methylene chloride, the methylene chloride solvent was distilled off, and the remaining liquid was extracted three times with 50 ml of a 10% aqueous sodium bisulfite solution. After gradually adding a dilute aqueous solution of caustic soda to the extract to make it weakly alkaline,
Extracted again three times with 100 ml of methylene chloride, dried over magnesium sulfate, and finally distilled under reduced pressure.
-Trifluoromethylbenzaldehyde 1.1g
(yield 13%). Comparative Example 2 Liquid of exactly the same raw material mixture as used in Example 4
10g and 32g of 87% sulfuric acid (sulfuric acid/raw material (molar ratio) =
When hydrolysis was carried out in the same manner as in Example 1, except that the reaction temperature was 100° C. and the reaction time was 2 hours, the formation of a tar-like compound was confirmed as in Comparative Example 1. The reaction solution was treated in the same manner as in Comparative Example 1 to obtain 3.0 g (yield: 36%) of o-trifluoromethylbenzaldehyde. Example 6 Liquid of exactly the same raw material mixture as used in Example 4
A hydrolysis reaction was carried out using 10 g under various conditions shown in Table 1, and the same post-treatment as in Comparative Example 1 was carried out. The results are also listed in Table 1 (yield and yield are shown for o-trifluoromethylbenzaldehyde).

【table】

[Table] Example 7 Using 10 g of the aromatic compound shown in Table 2 as a raw material,
The hydrolysis reaction was carried out under the reaction conditions shown in Table 3, and the same post-treatment as in Comparative Example 1 was carried out. The results are shown in Table 2 for the final product and Table 3 for the other results.
They are also listed in the table.

【table】

【table】

[Table] Comparative Examples 3 to 13 Liquid 10 of the same raw material mixture as that used in Example 4
A hydrolysis reaction was carried out under the various conditions shown in Table 4 using G. g, and the same post-treatment as in Example 1 was carried out. The results are listed in Table 4. Note that the yield and yield in Table 4 are shown for o-trifluoromethylbenzaldehyde.

【table】 [Brief explanation of drawings]

FIG. 1 is a graph plotting the results of each example. The "fruit" above the plot point indicates the example, the numerical value after it indicates the example number, and the "ratio"
indicates a comparative example, and the following numerical value indicates the comparative example number. The number below each plot point indicates the yield (%).

Claims (1)

[Claims] 1. At least one of the hydrogen atoms bonded to the basic skeleton of the aromatic compound is a trifluoromethyl group (-
CF ₃ ) and at least one of the other hydrogen atoms is each substituted with a dihalomethyl group represented by the general formula -CHXY (where X and Y are the same or different halogen atoms), concentration is 80
% or more of sulfuric acid and the reaction time is within 60 minutes, or sulfuric acid concentration (C weight %) and reaction time (t minutes)
is hydrolyzed under the conditions shown by the formulas (A); C=178/t+8+81 and (B) ; C=450/t+79 (however, 80≦C≦86.5, 60≦t≦100) A method for producing an aromatic compound having a trifluoromethyl group and an aldehyde group, characterized in that: 2. The method according to claim 1, wherein the amount of sulfuric acid used is 2 or more in terms of sulfuric acid/raw material aromatic compound (molar ratio). 3. The method according to claim 1, wherein the reaction temperature is in the range of 60 to 140°C. 4 The raw material aromatic compound has the general formula [Formula] (where Z is a hydrogen atom or a halogen atom, and 2
More than one species of halogen atoms may be bonded, n
is a positive integer from 1 to 5, j, k and l are integers from 0 to 5, m is an integer from 0 to 4, and n+j+k+l+m=
6. The method according to claim 1, wherein the fluorine-containing aromatic compound is a fluorine-containing aromatic compound represented by the following formula: 6, 5≧j+k+l≧1. 5. The method according to claim 1, wherein the sulfuric acid has a concentration of 85% or more. 6. The method according to claim 1, wherein the sulfuric acid concentration (C weight %) and the reaction time (t minutes) are selected between conditions represented by the following formulas (A)' and (B)'. (A)' C=178/t+8+81 (B)' C=450/t+79 (80≦C≦100, 0<t≦100) 7 Reaction time (t minutes) is 0<t≦60 The method according to claim 6.