JPS6122067A - Production of indole - Google Patents

Abstract

PURPOSE:In the production of an indole by the liquid-phase reaction between an aniline and a 1,2-glycol in the presence of a catalyst, cadmium and potassium bromide and/or iodide are used as a catalyst to enable the advantageous production of the objective compound. CONSTITUTION:The liquid-phase reaction between an aniline of formula I (R<1> is H, 1-4C alkyl, alkoxy, OH, halogen, NO2; R<2> is H, 1-4C alkyl) and a 1,2-glycol of formula II (R<1>-R<4> are H, 1-4C alkyl which may be substituted with, e.g., halogen, hydroxyl, CN) is conducted in the presence of a catalyst which is composed of CdX<1> and KX<2> (X<1>, X<2> are Br, I) at a molar KX<2>/CdX<1> ratio of 0.1-10, preferably 1-7, particularly preferably 2-5 to enable high-yield production of an indole which is used as a starting material for perfume with industrial advantage. The above catalyst can be readily recovered and reused with high performance.

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 include fragrances, amino acids such as tryptophan,
It is an industrially useful substance as a raw material for molecular stabilizers.

Prior Art As methods 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, as the catalyst used, Cu%Cr, C
o, Fe%Ni, Mu, Mn, At.

A dehydrogenation catalyst used for the dehydrogenation reaction of ordinary alcohols such as α, Pd, Pt, and Rh was disclosed in Japanese Patent Application Laid-Open No. 56-5365.
No. 2 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.
-55366, a copper-containing catalyst is disclosed in JP-A-56-1
69668 discloses a catalyst containing cadmium sulfide and/or zinc sulfide, JP-A-58-109471 discloses a cadmium chloride catalyst, and JP-A-58-12.12.7 discloses a catalyst containing cadmium sulfide and/or zinc sulfide.
No. 0 discloses a calcium sulfate-containing catalyst as disclosed in JP-A-58-
Patent No. 215062 proposes silver oxide-containing catalysts.

Furthermore, JP-A-58-46067 discloses a method in which indoles are produced by reacting anilines and 1,2-glycols in the presence of a catalyst, and 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 experimental examples are described.

Among the above-mentioned known methods, JP-A No. 58-46067 and No. 5
All methods other than those described in each publication of No. B-109471 are limited to gas phase methods. These two patents are based on gas phase,
It is disclosed that either a liquid phase method or a gas-liquid mixed phase method can be used. However, in all of the concrete experimental examples shown, reactions were carried out in the gas phase, and it is unclear whether a liquid phase method is possible.

Also, JP-A-56-73060 and JP-A No. 56-110672
The specification publication discloses a method for producing indoles in a liquid phase using Group 8 metals, magnesium oxide, etc. as catalysts, but according to the results of additional tests by the present inventors, the yield is insufficient. It was something.

On the other hand, with the 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 in order to restore the catalyst activity, complicated catalyst regeneration treatment operations are frequently performed. This method is unsatisfactory as an industrial production method because it has to be reactivated or cannot be reactivated depending on the catalyst, or the catalyst cost is high for silver-containing catalysts.

SUMMARY OF THE INVENTION The present inventors have conducted intensive studies to solve the above problems and have 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 catalyst used is CaX2 and KX2.
(However, Xl and f represent bromine or iodine, and Xl and x
'' may be the same or different).

According to the method of the present invention, a high indole yield can be obtained,
In addition, the used catalyst can be easily recovered and excellent performance can be reproduced even when the catalyst is reused, so that a practically excellent method is provided as an industrial production method.

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, R1 represents a hydrogen atom, a C1-4 alkyl group, an alkoxy group, a hydroxyl group, a hydrogen atom, or a nitro group, and W represents a hydrogen atom or a C1-4 alkyl group.

Specific examples of the anilines shown in (1) above include aniline, 0-toluidine, m-)luidine, p-toluidine, 0-aminephenol, m-aminophenol,
p-aminephenol, 0-anisidine, m-anisidine, p-anisidine, 〇-chloroaniline, m-chloroaniline, T'-roaniline, 0-nitroaniline, m-nitroaniline, p-nitroaniline, etc. be.

In the method of the present invention, for example, p
- When aminophenol is used, 5-hydroxyindole can be produced as an indole.

The 1,2-glycols used in the method of the present invention have the following general formula: (wherein R1, R11, R8 and R4 are hydrogen atoms or
)・represents an alkyl group of 01 to 4 which may be substituted with rogene, hydroxyl or cyan group, which may be the same or different from each other).

Examples of these include ethylene glycol, propylene glycol, 1,2-butanediol, 2,3-furinodiol, pinacol, glycerol, glycerol-2
-monochlorohydrin, glycerol-2-monocyanhydrin, etc.

1.2 - When using ethylene glycol, polyethylene glycols such as diethylene glycol may also be added to ethylene glycol within the range that does not adversely affect the yield of indoles, which are the target products of the present invention. However, it can be added within a range of 4 or less.

The catalyst used in the process of the invention comprises cadmium bromide and/or iodide (cax4, where Xl indicates bromine or iodine) and potassium bromide and/or iodide (K
XQ, where X2 represents bromine or iodine) 1 When this Cd elder brother and 1Kx2 are used in combination, the u''/CdX20 molar ratio is used in the range of 0.1 to 10, Preferably Fii~7, the above CdX: and KX
” may be added separately, or KCdX(2+a)
(However, X is bromine and/or iodine, and a is an integer of 1 to 4) may be prepared and then added.

Catalysts used in the method of the present invention may include, for example, those disclosed in Japanese Patent Application Laid-Open No.
The additive components described in the upper right column, line 10 on page 2 of Publication No. 8-225061 to the fourth line in the lower right column on the same page can be added.

The catalyst used in the method of the present invention is usually a combination of CdX and K.

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, such as 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 one reduced pressure. Furthermore, the liquid phase reaction with 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 nitrogen, hydrogen, ammonia,
Examples include gases such as carbon dioxide. When using these gases, they are preferably introduced into the reaction system in advance at a pressure of 0 to s o K9/'-. 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, and dimethyl sulfoxide. , pyridine, N-methylpyrrolidone, and other organic solvents.

Anilines and 1,2 as reaction raw materials used in the present invention
- Glycol does not need to be particularly pure; for example, in the case of alcohol, small amounts of nitrobenzene and phenol, which are usually present, may be contained, and in the case of ethylene glycol, for example, acetic acid or polyethylene glycol may be contained. 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 reaction system [in which anilines and 1,
The ratio of 2-glycols to 1 mole of aniline is:
1, 2. - 0.01 to 5 moles, preferably 0.02 to 2 moles. The amount of catalyst used is 1,2
-0.00 as cax4 per mole of glycols
The amount is 1 mole or more, preferably 0.01 to 10 moles, particularly preferably 0.05 to 0.05 mole.

The reaction temperature is 200-500°C, preferably 250-40°C.
It is 0°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/d.

After the reaction, most of the catalyst is separated by convenient means.

The separated catalyst is reused in the reaction. For the liquid, unreacted raw materials such as aniline and ethylene glycol are recovered by distillation 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 some convenient means and is reused in the reaction together with the catalyst. The above-mentioned operation is an example, and the operation procedure is not limited to this. For example, solvents such as carbon tetrachloride, chloroform, dichloromethane, dichloroethane, toluene, etc. may be used for separating and washing the catalyst. The recovered catalyst can be used as it is in the reaction, but if necessary, it can be regenerated and reused by washing with the above-mentioned solvent or by calcination in air.

Experimental Examples Example 1 Contents: 48.0 ml of aniline was placed in a stainless steel autoclave equipped with ``Hastelloy'' and a 100 l stirrer. (
0.52 mol), ethylene glycol 3.22 (0.0
52 mol), cadmium bromide 2.9 t (o,.

107 mol) and potassium bromide 3.7 F (0,0
311 mol) was introduced, the air in the autoclave was replaced with hydrogen gas, and the hydrogen gas was sealed at a pressure of 15 Kf/-, followed by reaction at a reaction temperature of 330° C. while stirring the 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. Reaction time is 1.2
It was time.

After the reaction, the catalyst was removed 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, "H-NMR$Pj and"C
- Generation of indole was confirmed by NMR. As a result, the conversion rate of indole 4.5i based on ethylene glycol was 9
9.89G, indole selectivity based on ethylene glycol 76.2.1.7 Indole selectivity based on diphosphorus s
1. The indole yield based on s To ethylene glycol was 76.0'4.

There were few by-products.

Example 2 An experiment was carried out in the same manner as in Example 1, except that the amount of potassium bromide was changed to 1.2 f and the reaction time was changed to 1.4 hours. As a result, the conversion rate based on ethylene glycol was 99-51, Indole selectivity based on ethylene glycol -, ee, 6%, Indole selectivity based on aniline? 5.44, yield based on ethylene glycol 66.3
I got the result.

Example 3 Cadmium iodide 3.8f, potassium iodide 1.7
An experiment was carried out in the same manner as in Example 1, except that 2 was used and the reaction time was changed to 1.5 hours. The conversion rate was 99.8% based on ethylene glycol, and the indole selectivity was 63.9 based on ethylene glycol. %, indole selectivity based on aniline 75.4%, yield based on ethylene glycol 6
The result was 3.8%.

Example 4 Cadmium iodide a,sy (0,0104 mol)
An experiment was conducted in the same manner as in Example 1, except that 5.2.9 (0,0313 mol) of potassium iodide was used and the reaction time was changed to 1.5 hours.The conversion rate was 99% based on ethylene glycol. .6%, selectivity based on ethylene glycol 67,! In, indole selectivity based on aniline standard: 80
．． The yield was 67.3% based on ethylene glycol.

Example 5 In Example 1, the amount of potassium bromide was changed to 5. When the experiment was conducted in the same manner as in Example 1 except that the reaction time was changed to 1.9 hours, the conversion rate based on ethylene glycol was 9.
9.5%, indole selectivity based on ethylene glycol 71.2φ, indole selectivity based on aniline 82.0
'%, yield of 70.8'1 based on ethylene glycol was obtained.

Example 6 Equimolar amounts of cadmium bromide were added to an aqueous solution of potassium bromide, heated and stirred at 80 to 90°C for 3 hours, the solution was concentrated under reduced pressure, and the precipitated solid was washed with ethanol to form KCdB.
Crystals of ra were obtained. The same experiment was conducted except that KCdBrs was used in an equimolar amount as the cadmium bromide used in Example 1, and the reaction time was changed to 1.4 hours.

As a result, the conversion rate was 99.4% based on ethylene glycol.
, indole selectivity based on ethylene glycol 65.1
%, the indole selectivity based on aniline was 84.0%, and the yield based on ethylene glycol was 64.7%.

Example 7 An experiment was carried out in the same manner as in Example 1, except that 0-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 was 99.7%.
, 7-methylindole selectivity based on ethylene glycol 79.0%, 7-methylindole selectivity based on aniline s 3.2. %, yield of 78.81 based on ethylene glycol was obtained.

Example 8 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 to 3 hours. A similar experiment was conducted, and the conversion rate was 99.6% based on ethylene glycol, the indole selectivity was 73.1% based on ethylene glycol, the indole selectivity was 84.9% based on aniline, and the indole yield was based on ethylene glycol. The result was a rate of 72.8%.

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 sample.

As a result, the conversion rate was 98.9% based on ethylene glycol.
, indole selectivity based on ethylene glycol 73.0
%, indole selectivity based on aniline 8 = 4.59g
, Indole vehicle collection based on ethylene glycol standard 72.21
I got the result.

Comparative examples 1 to 9 The results are shown in Table 1.

(Left below) Example 9 In Example VAl 1, the amount of aniline used was 24. o? (
The experiment was conducted in the same manner as in Example 1, except that the reaction time was changed to 0.26 mol) and 2 hours.

As a result, the conversion rate based on ethylene glycol was 99.84.
, indole selectivity based on ethylene glycol 69.3
H. Indole selectivity based on aniline was 82.51, and indole yield based on ethylene glycol was 69.2'1.

Claims (2)

[Claims] (1) In a method for producing indoles by reacting anilines and 1,2-glycols in a liquid phase in the presence of a catalyst, the catalysts used are CdX^1_2 and KX^2 (however, X^1 and X^2
represents bromine or iodine, and X^1 and X^2 may be the same or different. (2) Molar ratio of catalyst used (KX^2/CdX^1_
2) A method according to claim 1, characterized in that 2) is in the range of 0.1 to 10 mol.