JPH0343267B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Field of Application] The present invention relates to a novel method for producing indole or indole derivatives from anilines and 1,2-glycols. [Prior Art] As a conventional method for producing indole derivatives, Fischer's indole synthesis method, which involves reacting phenylhydrazine with a compound having an aldehyde group, is well known. However, if the aldehyde compound is other than acetaldehyde, the above-mentioned Fuitscher indole synthesis method can be applied and an indole derivative can be obtained in high yield, but if the aldehyde compound is acetaldehyde, the reaction does not proceed and the indole is It was said that it would not be generated. As a method to improve this method, a method has recently been proposed in which phenylhydrazine and acetaldehyde are reacted at a high temperature of 300 to 400° C. to form an alumina catalyst (Japanese Patent Application Laid-Open No. 76864/1983). In this method, the reaction certainly progresses and indole is produced, but the yield is not sufficient and the life of the catalyst is extremely short.
A major drawback was that the catalyst was completely deactivated after ~1 hour of use. In addition, as another indole production method, ortho-
By reacting toluidine with formic acid, ortho-methyl-
There is a method of producing N-formylaniline and melting it with potassium hydroxide. In this method, the ortho-toluidine used as a starting material usually contains the same amount or more of the para-isomer as the ortho-isomer. Therefore, processing of isomers co-produced as by-products becomes a major problem during industrial production. Furthermore, handling of solids such as alkali melting is complicated, and it is difficult to say that it is suitable for industrial production. Furthermore, several attempts have been made to synthesize indole from N-β-hydroxyethylaniline, but these have not been satisfactory as an industrial production method. For example, a method of heating together with a mixed molten salt mainly consisting of molten zinc chloride,
No. 48-57968) has a fairly high indole yield, but has the disadvantage that the reaction operation is complicated, and is not preferred as an industrial production method. As mentioned above, there have been several proposed methods for synthesizing indoles, but they all produce many by-products, are expensive raw materials, and require a long process to produce indoles. long,
Many of them are complicated to operate. [Problems to be Solved by the Invention] An object of the present invention is to provide a method for producing indole or an indole derivative with high selectivity using inexpensive raw materials and in a single step. [Means for Solving the Problems] The present invention provides the following method for producing indole or an indole derivative. Anilines and 1,2-glycols are combined with Si,
Al, B, Sb, Bi, Sn, Pb, Ga, Ti, Zr, Be,
Oxide or hydroxide of at least one element selected from Y, Cu, Ag, Zn, Cd and lanthanide elements, Pd, Pt, Cr, Fe, Ni, Co, Zn,
Sulfide or selenide of at least one element selected from Mo, Cd and W, or Fe,
Tl, Ca, Mn, Bi, Pb, Sr, Y, Al, Zn, Cd,
A solid acid catalyst containing an inorganic salt of at least one element selected from Ni, Mg, In, Be, Co, Ga and lanthanide elements and not containing magnesium oxide, Cu, Ag, Pt, Pd, Ni, Co, Fe, Ir,
A method for producing indole or an indole derivative containing at least one element selected from Os, Ru, and Rh, characterized in that the reaction is carried out in a liquid phase in the presence of a metal catalyst or activated carbon that does not contain magnesium oxide. According to this reaction method, for example, indole can be obtained by reacting aniline with ethylene glycol, and 5-methylindole can be obtained by reacting paratoluindi with ethylene glycol. The anilines used in the method of the present invention have the general formula () (wherein R represents a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, or an alkoxy group). For example, aniline, ortho-toluidine, meta-toluidine, para-toluidine, istho-haloaniline, meta-haloaniline, para-haloaniline, ortho-aminophenol, meta-aminophenol, para-aminophenol, ortho-anisidine, meta-anisidine. , para-anisidine, etc. The 1,2-glycols used in the method of the present invention include ethylene glycol, propylene glycol, 1,2-butanediol, 1,2,4-butanetriol, 2,3-butanediol, diethylene glycol, and the like. In the present invention, the following solid acid catalyst, metal catalyst, or activated carbon is used as a catalyst. None of these catalysts contain magnesium oxide. The solid acid catalysts used in the method of the present invention include (1) Si, Al, B, Sb, Bi, Sn, Pb, Ga, ,Ti,
Oxide or hydroxide of at least one element selected from Zr, Be, Y, Cu, Ag, Zn, Cd and lanthanide elements (hereinafter referred to as catalyst material (1)
) but not magnesium oxide, e.g., CdO, ZnO-Sb ₂ O,
PbO ₂ , Al ₂ O ₃ −B ₂ O ₃ , SiO ₂ −CdO, SiO ₂ −
Al ₂ O ₃ , TiO ₂ −SnO ₂ , TiO ₂ −ZrO ₂ , CdO−
Bi ₂ O ₃ , SiO ₂ −Y ₂ O ₃ , SiO ₂ , Bi ₂ O ₃ −BeO,
SiO ₂ −La ₂ O ₃ , SiO ₂ −Ce ₂ O ₃ , SiO ₂ −ZnO−
AgO, SiO ₂ −Ga ₂ O _3, etc., (2) Pd, Pt, Cr, Fe, Ni, Co, Zn, Mo, Cd,
and a catalyst containing sulfide or selenide of at least one element selected from W (hereinafter referred to as catalyst material (2)) but not containing magnesium oxide, such as PdS, PtS, CrS, FeS,
CoS, ZnS, MoS ₂ , CdS, WS ₂ , ZnSe, CdSe
etc., (3) Fe, Tl, Ca, Mn, Bi, Pb, Sr, Y, Al,
Inorganic salts of at least one element selected from Zn, Cd, Ni, Mg, In, Be, Co, Ga and lanthanide elements, i.e. halides, carbonates, nitrates, sulfates, phosphates, pyrophosphates , phosphomolybdate, silicotungstate, (hereinafter referred to as catalyst substance (3)) but not magnesium oxide, such as ferric sulfate, thallium sulfate, calcium sulfate, manganese sulfate, sulfuric acid Bismuth, cadmium sulfate, strontium sulfate, yttrium sulfate, cadmium bromide, aluminum sulfate, zinc sulfate, nickel sulfate, cadmium chloride, magnesium sulfate, indium sulfate, beryllium sulfate, cadmium nitrate, cobalt sulfate, zinc aluminum sulfate, cadmium phosphate, Cadmium iodide, lead iodide, magnesium chloride, etc. Metal catalysts include Cu, Ag, Pt, Pd,
Examples include catalysts that contain at least one element selected from Ni, Co, Fe, Ir, Os, Ru, and Rh (hereinafter referred to as catalyst material (4)) but do not contain magnesium oxide. The solid acid catalyst or metal catalyst used in the method of the present invention can be produced by any method known in the art. Specifically, catalyst material (1) among solid acid catalysts can be prepared by hydrolyzing water-soluble salts of catalyst constituent elements to form hydroxides, drying and calcining the resulting gel, or by drying and baking liquid-decomposable salts in the air. It can be produced by a method such as thermal decomposition. Catalyst material (2) among solid acid catalysts can be obtained by adding sodium sulfide or potassium selenide to a water-soluble salt of a catalyst constituent element, or by contacting a catalyst constituent element or its salt with hydrogen sulfide gas or hydrogen selenide gas. It can be manufactured by etc. Furthermore, the catalyst substance (4), which is a metal catalyst, converts salts, hydroxides, or oxides of catalyst constituent elements into hydrogen,
It can be produced by a method of reducing with a reducing agent such as formalin, formic acid, phosphorous acid, or hydrazine. The method of the present invention is a liquid phase reaction, and as is clear from the reaction formula, water is produced, so some or all of the inorganic salt of the catalyst substance (3) is dissolved under the reaction conditions. It is thought that some of the moieties act as catalysts that promote the reaction of the present invention. Further, the metal catalyst may also be a soluble salt or a complex. The solid acid catalyst or metal catalyst used in the method of the present invention may be one of the above catalyst substances (1), (2), (3), and (4), or a mixture of two or more thereof. good. Further, in order to effectively utilize the inherent activity of these catalytic substances, a method of supporting these catalytic substances as collateral is also preferably used, which is a method commonly used in this technical field. As a carrier,
Any commonly used materials can be used, but materials other than magnesium oxide are usually used, such as diatomaceous earth, pumice, titania, silica alumina, alumina, silica gel, activated carbon, activated clay, and asbestos. A supported catalyst is prepared by supporting the catalyst substance on these carriers by a conventional method. There is no particular restriction on the amount of the catalyst substance supported on the carrier,
Generally, depending on the carrier, a suitable amount of the catalyst material may be supported, for example 1 to 50%. In addition to the method of supporting the inorganic salt of the catalyst substance (3) on a carrier, which is a method adopted as necessary in this technical field, it is possible to form a molten salt and make contact with the reaction raw materials under strong stirring. Alternatively, a method that facilitates surface renewal and prevents a decrease in catalytic activity may be used.
Additives for forming molten salts are commonly used. Any substance that forms a double salt with the catalyst substance (3) and has the effect of lowering the melting point can be used. Such additives typically include alkali metal halides, alkaline earth metal halides, alkali metal nitrates, and the like. The molten salt formed is, for example, KCl-
FeCl ₃ , KBr−CaBr ₂ , KI−BiI ₃ , KI−PbI ₂ ,
Examples include _BaI2 - _PbI2 , KCl- _AlCl3.Kbr - _NiBr2 , and the like. The activated carbon used in the method of the present invention is of various types, such as activated carbon made from coconut shells, wood, sawdust, lignin, coal, blood char, bone char, petroleum carbon, and the like. Commercially available activated carbon is usually powdered carbon, crushed carbon, or molded carbon shaped into a spherical or cylindrical shape, but there are no particular restrictions on the shape of the activated carbon used. The process according to the invention is carried out in liquid phase or in a gas-liquid mixed phase.
The reaction is carried out by heating a mixture of anilines and 1,2-glycols in the presence of one or more catalysts selected from the above catalysts. At this time, various inert gases and/or solvents can be used as diluents for the raw materials. Examples of such inert gaseous substances include nitrogen gas, carbon dioxide, water vapor, and vapors of compounds inert to this reaction. Examples of the solvent include benzene, toluene, xylene, hexane, octane, liquid paraffin, methanol, ethanol, isopropanol, dioxane, dimethylformamide, dimethyl sulfoxide, pyridine, N-methylpyrrolidone, trimethylamine, diethylamine, triethylamine, tripropyl. Examples include organic solvents such as amine, tributylamine, diphenylamine, and triphenylamine. This liquid phase reaction is carried out in a stationary phase, fluidized bed or moving bed reactor, batch type or continuous type liquid phase reactor, but is not particularly limited. In this reaction, the amounts of anilines and 1,2-glycols used as raw materials are 0.05 to 5 mol of 1,2-glycols per mole of aniline.
in the molar range, preferably in the range of 0.1 to 2 molar. Furthermore, the reaction temperature is in the range of 100-500°C, preferably in the range of 150-400°C. If the temperature is lower than 100°C, the reaction will hardly proceed, and if the temperature exceeds 500°C, a large amount of by-products will be produced, which is not preferable. Further, the reaction pressure may be either elevated pressure or normal pressure. In the method of the present invention, indole or an indole derivative can be easily separated and purified from the reaction product by an appropriate method, for example, a conventional method such as distillation. [Example] The method of the present invention will be further explained with reference to Examples below. Example 1 93.1 g (1 mol) of aniline, 12.4 g (0.2 mol) of ethylene glycol, and 2 g of powdered palladium-activated carbon catalyst (Pd content 0.5% by weight) were placed in a titanium alloy autoclave with an internal volume of 200 ml and equipped with a stirrer. After replacing the air in the autoclave with nitrogen gas and filling the autoclave with a nitrogen pressure of 5°C/ ^cm2 , the reaction temperature was
The reaction was carried out at 300°C for 30 minutes while stirring in an autoclave. After the reaction, the catalyst was filtered from the reaction solution and the reaction product was analyzed by gas chromatography, and it was found that indole was produced at a yield of 38% based on ethylene glycol. Example 2 The same reaction as in Example 1 was carried out, the amount of ethylene glycol was reduced to 6.1 g (0.1 mol), the catalyst was changed to 4 g of powdered Ag/SiO ₂ -ZnO (Ag supported amount: 11% by weight), and nitrogen Instead of gas, hydrogen gas was sealed at 5 kg/cm ² , and the reaction temperature was changed to 370° C. and the reaction time was changed to 15 minutes. After the reaction, the catalyst was filtered from the reaction solution and the reaction product was analyzed by gas chromatography, and it was found that indole was produced at a yield of 82.3% based on ethylene glycol. There were few by-products. Example 3 The same reaction as in Example 1 was carried out by changing the catalyst to 0.3 g of ruthenium chloride and 1.2 g of triphenylphosphine, changing the reaction temperature to 200° C., and changing the reaction time to 4 hours. Analysis of the reaction product using gas chromatography revealed that the yield was based on ethylene glycol.
It was confirmed that indole was produced at 2.1%. Example 4 The same reaction as in Example 1 was carried out except that the catalyst was changed to that shown in Table 1, the reaction temperature was 270°C, and the reaction time was 1.
I did it on time. The reaction products were analyzed by gas chromatography. Table 1 shows the results.

【table】

【table】

[Table] [Effects of the Invention] The advantages of the method of the present invention are: firstly, the raw materials are very inexpensive such as anilines and 1,2-glycols, and secondly, indole or indole derivatives can be obtained from the raw materials in one step. Manufactured. Thirdly, there are very few by-products, high selectivity, and highly pure indole or indole derivatives can be obtained.

Claims (1)

[Claims] 1 Anilines and 1,2-glycols,
Si, Al, B, Sb, Bi, Sn, Pb, Ga, Ti, Zr,
Oxide or hydroxide of at least one element selected from Be, Y, cu, Ag, Zn, Cd and tantanide elements, Pd, Pt, Cr, Fe, Ni, Co,
Sulfide or selenide of at least one element selected from Zn, Mo, Cd and W, or
Fe, Tl, Ca, Mn, Bi, Pb, Sr, Y, Al, Zn,
A solid acid catalyst containing an inorganic salt of at least one element selected from Cd, Ni, Mg, In, Be, Co, Ga and lanthanide elements and not containing magnesium oxide, Cu, Ag, Pt, Pd, Ni, Co, Fe, Ir,
A method for producing indole or an indole derivative, which comprises carrying out a liquid phase reaction in the presence of a metal catalyst or activated carbon that contains at least one element selected from Os, Ru, and Rh and does not contain magnesium oxide.