JPH0510341B2 - - Google Patents

Description

[Detailed description of the invention]

FIELD OF THE INVENTION The present invention relates to a method for producing indoles by catalytically reacting anilines and 1,2-glycols. According to the method of the present invention, indoles can be industrially advantageously produced in high yield. Indoles are industrially useful substances as raw materials for perfumes, amino acids such as tryptophan, and molecular stabilizers. Prior Art As a method for producing indoles by reacting anilines and 1,2-glycols in the presence of a catalyst, methods using various catalysts have been proposed.
For example, the catalysts used in JP-A-56-36451 include Cu, Cr, Co, Fe, Ni, Zn, Mn, Al,
A dehydrogenation catalyst used for the dehydrogenation reaction of ordinary alcohols such as Ca, Pd, Pt, and Rh was disclosed in Japanese Patent Application Laid-Open No. 56-53652.
The publication discloses a catalyst containing cadmium sulfate and/or zinc sulfate, and JP-A-56-46865 discloses a catalyst containing cadmium chloride and/or zinc chloride.
JP-A No. 56-55366 uses a copper-containing catalyst, and JP-A No. 56-169668 uses cadmium sulfide and/or
Alternatively, a catalyst containing zinc sulfide is used;
No. 121270 proposes a calcium sulfate-containing catalyst, and JP-A-58-225062 proposes a silver oxide-containing catalyst. Furthermore, JP-A-58-46067 discloses a method for producing indoles by reacting anilines and 1,2-glycols in the presence of a catalyst, in which the reaction is carried out in the presence of water and hydrogen. is disclosed.
Although cadmium halides are disclosed as one example of a large number of catalysts used in this method, there is no specific description of whether cadmium iodide can be used, and no specific examples are described. Among the above-mentioned known methods, JP-A No. 58-46067 and the same
All methods other than those described in each publication of No. 58-109471 are limited to gas phase methods. These two patents are
It is disclosed that any of the gas phase, liquid phase, and gas-liquid mixed phase methods can be used. However, all of the concrete experimental examples shown involve reactions in the gas phase, and it is unclear whether a liquid phase method is possible. In addition, Japanese Patent Application Laid-open Nos. 56-73060 and 56-110672 disclose a method for producing indoles in a liquid phase using Group 8 metals, magnesium oxide, etc. as catalysts, but the present invention According to the results of additional tests conducted by the inventors, the yield was insufficient. On the other hand, with known catalysts used to produce indoles by the gas phase method, even if the yield of indole is high, the catalytic activity decreases significantly, and complicated catalyst regeneration treatment operations are often required to restore the catalyst activity. This method is unsatisfactory as an industrial production method, as it has problems such as catalyst costs, such as the inability to reactivate depending on the catalyst, or the high cost of silver-containing catalysts. SUMMARY OF THE INVENTION The present inventors conducted intensive studies to solve the above problems and completed the present invention. That is, the present invention provides a method for producing indoles by reacting anilines and 1,2-glycols in a liquid phase in the presence of a catalyst, in which the catalysts used are CdX ¹ ₂ and KX ² (however, X ¹ and X ² represent bromine or iodine, and X ¹ and X ² may be the same or different. According to the method of the present invention, a high indole yield can be obtained, the used catalyst can be easily recovered, and excellent performance can be reproduced even when this catalyst is reused, so it is not practical as an industrial production method. A better method is provided. DETAILED DESCRIPTION OF THE INVENTION The anilines used in the method of the present invention are preferably compounds represented by the following general formula. However, in the formula, R ¹ is a hydrogen atom, a C _1-4 alkyl group,
Alkoxy group, hydroxyl group, halogen atom,
It represents a nitro group, and ^R2 represents a hydrogen atom or a _C1-4 alkyl group. Specific examples of the anilines shown in (1) above include aniline, o-toluidine, m-toluidine, p-toluidine, o-aminophenol, m
-aminophenol, p-aminophenol, o
-anisidine, m-anisidine, p-anisidine, o-chloroaniline, m-chloroaniline,
p-chloroaniline, o-nitroaniline, m-
Examples include nitroaniline and p-nitroaniline. When, for example, p-aminophenol is used as the raw aniline in the method of the present invention, 5-hydroxyindole can be produced as the indole. The 1,2-glycols used in the method of the present invention have the following general formula: (In the formula, R ¹ , R ² , R ³ and R ⁴ are hydrogen atoms or
It is a dihydric alcohol represented by _C1-4 alkyl group which may be substituted with halogen, hydroxyl group or cyano group, which may be the same or different from each other. Examples of these include ethylene glycol, propylene glycol, 1,2-butanediol,
2,3-butanediol, pinacol, glycerol, glycerol-2-monochlorohydrin,
Glycerol-2-monocyanhydrin and the like. When ethylene glycol is used as the 1,2-glycol, polyethylene glycol, which is a diethylene glycol, may also be used in a range that does not adversely affect the yield of indoles, which are the target products of the present invention, for example, in a range of 50 wt% or less based on ethylene glycol. It can be added with. The catalysts used in the process of the present invention are cadmium bromide and/or iodide (CdX ¹ ₂ , where X ¹ represents bromine or iodine) and potassium bromide and/or iodide.
or a combination of iodides (KX ² , where X ² represents bromine or iodine). This CdX ¹ ₂ and
When used in combination with KX ² , the molar ratio of KX ² /CdX ¹ ₂ is used in the range of 0.1 to 10, preferably 1
-7, particularly preferably 2-5. The above CdX ¹ ₂ and KX ² may be added separately,
A compound such as KCdX _(2+a) (where X is bromine and/or iodine, and a is an integer of 1 to 4) may be prepared in advance and then added. The catalyst used in the method of the present invention may include, for example, JP-A-58-225061, page 2, upper right column 10
It is possible to add the additive components listed in line 4 to line 4 of the lower right column of the same page. The catalyst used in the method of the present invention is CdX ¹ ₂ and KX ²
A combination of these is usually used as is as a catalyst. Moreover, it can also be used by being supported on a carrier by a conventional method. As this carrier, those commonly used as carriers for supported catalysts can be used, but
For example, alumina, silica, activated carbon, silica-alumina, silica gel, activated clay, diatomaceous earth, pumice, etc. are used. The method of the invention is carried out in the liquid phase. This liquid phase reaction can be carried out using either a batch type, non-batch type or continuous type reactor.
Further, the reaction can be carried out under any pressure including increased pressure, normal pressure and hydraulic pressure. Furthermore, this liquid phase reaction can be carried out in the absence or presence of a diluent. In the latter case, various inert gases and/or solvents can be used as diluents. Examples of such inert gaseous substances include gases such as nitrogen, hydrogen, ammonia, and carbon dioxide. When using these gases, they are preferably introduced into the reaction system in advance at a pressure of 0 to 50 kg/cm ² . The solvent is not particularly limited as long as it does not adversely affect the reaction, but examples include hydrocarbons such as benzene, toluene, and xylene, trialkylamines such as trimethylamine,
Triphenylamine, dioxane, dimethylformamide, dimethyl sulfoxide, pyridine, N
- Examples include organic solvents such as methylpyrrolidone. The anilines and 1,2-glycols used as reaction raw materials in the present invention do not need to be of particularly high purity; for example, aniline usually contains small amounts of nitrobenzene and phenol, and ethylene glycol contains acetic acid, polyethylene glycol, etc. May be included. Other hydrocarbons and derivatives thereof may also be included as long as they do not adversely affect the reaction. Although water is generated during the reaction, if it is present in the reaction system from the beginning, the yield may be slightly lowered, so it is better not to include water in the raw materials as much as possible. In the method of the present invention, the ratio of aniline and 1,2-glycol in the reaction system is 0.01 to 5 mol, preferably 0.02 to 2 mol, of 1,2-glycol per 1 mol of aniline. The amount of catalyst used is per mole of 1,2-glycols.
0.001 times mole or more as CdX ¹ ₂ , preferably 0.01~
The amount is 10 times the mole, particularly preferably 0.05 to 0.5 mole.
The reaction temperature is 200-500°C, preferably 250-400°C. When hydrogen is allowed to coexist in the reaction system as a diluent, it can be introduced into the reaction system in advance at a pressure of 0 to 50 kg/cm ² . After the reaction, most of the catalyst is separated by filtering or other means. The separated catalyst is reused for the reaction. For the liquid, unreacted raw materials such as aniline and ethylene glycol are recovered by distillation, etc., and reused in the reaction.
Next, the products such as indole are separated and purified by distillation or the like. The catalyst is recovered from the residue by means such as filtration and reused in the reaction together with the catalyst. The above operation is an example, and the operation procedure is not limited to this. Solvents such as carbon tetrachloride, chloroform, dichloromethane, dichloroethane, and toluene can be used to separate and wash the catalyst. The recovered catalyst can be used in the reaction as it is, but if necessary, it can be regenerated by washing with the above-mentioned solvent or calcined in air, and then reused. Experimental Examples Example 1 Contents: 48.0 g of aniline in a 100 ml stainless steel autoclave with a “Hastelloy” agitator.
(0.52 mol), ethylene glycol 3.2 g (0.052 mol), cadmium bromide 2.9 g (0.0107 mol) and potassium bromide 3.7 g (0.0311 mol) were introduced, and the air in the autoclave was replaced with hydrogen gas. was sealed at a pressure of 15Kg/ ^cm2 , and the reaction temperature was increased to 330℃.
The reaction was carried out at ℃ while stirring in an autoclave.
As the reaction progresses, the autoclave pressure increases due to hydrogen gas and water vapor generated. The reaction was considered to have ended when this pressure increase stopped. The reaction time was 1.2 hours. After the reaction, the catalyst was separated from the reaction solution, and the reaction product was analyzed by gas chromatography. The product was also isolated by distillation, and the melting point, IR, 1H−
The formation of indole was confirmed by NMR and 13C-NMR. As a result, indole was 4.5 g, conversion rate was 99.8% based on ethylene glycol, indole selectivity was 76.2% based on ethylene glycol, indole selectivity was 81.8% based on aniline, and indole yield was 76.0% based on ethylene glycol. There were few by-products. Example 2 In Example 1, the amount of potassium bromide was changed to 1.2 g,
The experiment was carried out in the same manner as in Example 1, except that the reaction time was changed to 1.4 hours. The conversion rate was 99.5% based on ethylene glycol, the indole selectivity was 66.6% based on ethylene glycol, and the indole selectivity was based on aniline. The yield was 75.4%, and the yield was 66.3% based on ethylene glycol. Example 3 Cadmium iodide 3.8g, potassium iodide 1.7g
The experiment was carried out in the same manner as in Example 1, except that the reaction time was changed to 1.5 hours. The conversion rate was 99.8% based on ethylene glycol, the conversion rate was 99.8% based on ethylene glycol, and the indole based on ethylene glycol was 99.8%. Results were obtained with a selectivity of 63.9%, an indole selectivity of 75.4% based on aniline, and a yield of 63.8% based on ethylene glycol. Example 4 An experiment was conducted in the same manner as in Example 1 except that 3.8 g (0.0104 mol) of cadmium iodide and 5.2 g (0.0313 mol) of potassium iodide were used and the reaction time was changed to 1.5 hours. Conversion rate of 99.6% based on glycol, selectivity based on ethylene glycol
67.5%, indole selectivity based on aniline 80.6
%, yield of 67.3% based on ethylene glycol was obtained. Example 5 In Example 1, the amount of potassium bromide was changed to 5.0 g,
The experiment was conducted in the same manner as in Example 1, except that the reaction time was changed to 1.9 hours, and the conversion rate was 99.5% based on ethylene glycol, the indole selectivity based on ethylene glycol was 71.2%, and the indole selectivity based on aniline was 82.0. %, yield of 70.8% based on ethylene glycol was obtained. Example 6 Equimolar amounts of cadmium bromide were added to an aqueous potassium bromide solution, heated and stirred at 80 to 90°C for 3 hours, and then
The solution was concentrated under reduced pressure, and the precipitated solid was washed with ethanol to obtain crystals of KCdBr ₃ . The same experiment was conducted except that KCdBr ₃ was used in an equal molar amount to the cadmium bromide used in Example 1, and the reaction time was changed to 1.4 hours. As a result, the conversion rate of ethylene glycol standard
99.4%, indole selectivity based on ethylene glycol 65.1%, indole selectivity based on aniline
The yield was 83.0%, and the yield was 64.7% based on ethylene glycol. Example 7 An experiment was carried out in the same manner as in Example 1, except that o-toluidine was used instead of aniline and the reaction time was changed to 1.7 hours. As a result, the conversion rate of ethylene glycol standard
The yield was 99.7%, the selectivity for 7-methylindole was 79.0% based on ethylene glycol, the selectivity for 7-methylindole was 83.2% based on aniline, and the yield was 78.8% based on ethylene glycol. Example 8 Same as Example 1 except that the residue after removing excess aniline and produced indole from the reaction product obtained in Example 1 by distillation was used as a catalyst and the reaction time was changed to 1.3 hours. When I conducted an experiment, I found that
Results were obtained such as a conversion rate of 99.6% based on ethylene glycol, an indole selectivity of 73.1% based on ethylene glycol, an indole selectivity of 84.9% based on aniline, and an indole yield of 72.8% based on ethylene glycol. Using this reaction product, the catalyst was recovered in the same manner as described above, and the experiment was conducted again in the same manner as above using this recovered catalyst. As a result, the conversion rate of ethylene glycol standard
98.9%, indole selectivity based on ethylene glycol 73.0%, indole selectivity based on aniline
The yield of indole was 84.5%, and the yield of indole was 72.2% based on ethylene glycol. Comparative Examples 1 to 9 Reactions were carried out in the same manner as in Example 1, except that the catalysts shown in Table 1 were used and the reaction times shown in Table 1 were used. The results are shown in Table 1.

[Table] Example 9 The amount of aniline used in Example 1 was 24.0g.
(0.26 mol) and the reaction time was changed to 2 hours.
All experiments were conducted in the same manner as in Example 1. As a result, the conversion rate of ethylene glycol standard
99.8%, indole selectivity based on ethylene glycol 69.3%, indole selectivity based on aniline
The yield of indole was 82.5%, and the yield of indole was 69.2% based on ethylene glycol.

Claims (1)

[Claims] 1. A method for producing indoles by reacting anilines and 1,2-glycols in a liquid phase in the presence of a catalyst, in which the catalyst used is CdX ¹ ₂ and
KX ² (However, X ¹ and X ² represent bromine or iodine,
X ¹ and X ² may be the same or different). 2 The molar ratio of the catalyst used (KX ² /CdX ¹ ₂ ) is 0.1
2. A method according to claim 1, characterized in that the amount is in the range .about.10 moles.