CA1150729A - Process for the preparation of indole and derivatives thereof - Google Patents
Process for the preparation of indole and derivatives thereofInfo
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- CA1150729A CA1150729A CA000375821A CA375821A CA1150729A CA 1150729 A CA1150729 A CA 1150729A CA 000375821 A CA000375821 A CA 000375821A CA 375821 A CA375821 A CA 375821A CA 1150729 A CA1150729 A CA 1150729A
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- catalyst
- indole
- oxide
- glycol
- aniline
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Abstract
SPECIFICATION
Title of the Invention Process for the Preparation of Indole and Derivatives Thereof Abstract of the Disclosure A process for the preparation of indole and derivatives thereof wherein an aniline is reacted with a 1,2-glycol in the vapor phase, the liquid phase or a mixed vapor-liquid phase under the influence of a copper-containing catalyst. The present invention makes it possible to prepare indole and derivatives thereof in a single step by using inexpensive compounds as the starting materials.
Title of the Invention Process for the Preparation of Indole and Derivatives Thereof Abstract of the Disclosure A process for the preparation of indole and derivatives thereof wherein an aniline is reacted with a 1,2-glycol in the vapor phase, the liquid phase or a mixed vapor-liquid phase under the influence of a copper-containing catalyst. The present invention makes it possible to prepare indole and derivatives thereof in a single step by using inexpensive compounds as the starting materials.
Description
2~
~ , Background of the Inven~ion i i 1) Field of the Invention This invention relates to a novel process for the preparation of indole and derivatives thereof by reacting ~, an aniline with a 1,2-glycol in the presence of a copper-containing catalyst.
.j 2) Description of the PrioT Art i ll In the prio~ art, indole derivatives have long been prepared by the well-known Fischer indole synthesis in which phenylhydrazine is reacted with a compound having an aldehyde group. If the aldehyde compo~und is other than acetaldehyde, the aforesaid Fischer indole synthesis can be I , , .
~L~5~7 ' applied to obtain indole derivatives in good yield. However~
if the aldehyde compound is acetaldehyde, no reaction that yields indole has been believed to take place. In order to overcome this disadvantage, there has recently been proposed an improved process which comprises reacting phenylhydrazine with acetaldehyde at an elevated temperature of from 300 to 400C in the presence of an alumina catalyst (Japanese Patent Laid-Open No. 76864/'73).
This process surely permits the reaction to pro-ceed and brings about the formation of indole J but fails to give a satisfactory yield. Moreover, it is greatly dis-advantageous in that the catalyst has so short a life as to become totally inacti~e after 0.5-1 hour's use.
Indole can also be prepared by another process which comprises reacting o-toluidine with -formic acid to form o-methyl-N-formylaniline and then fusing it together with potassium hydroxide. However, it is usually impossible to selectively prèpare o-toluidine that is used as the starting material in this process. That is, the ~-isomer is always formed in an amount equal to or greater than that of the o-isomer. Thus, treatment of the isomer formed as a by-product poses a serious problem in the case of indus-trial production. Moreover, the handling of solids as in alkali fusion is troublesome. For these reasons, the aforesaîd process cannot be regarded as suitable for indus-trial purposes.
Furthermore~ a number of attempts have been made to synthesize indole from N~ -hydroxyethylamine, but none , , ,, .
72~
o them are satisfactory from an industrial point of view.
For example, a process which comprises effecting the ; reaction at 30UC in the presence of an aluminosilicate catalyst [Zhur. Obschue. Khim., Vol. 24, pp. 671-678 (1954)]
gives only a very low yield of indole. A process which comprises heating the reactant together with a molten mixed salt consisting mainly of zinc chloride (Japanese Patent Laid-Open No. 57968/'73) can give a fairly high yield of indole. However, this process has the disadvantage of requiring a complicated procedure, which makes it unsuitable ~I for industrial purposes.
l~ ~s described above, a number of processes for the ¦ synthesis of indole and derivatives thereof have been ; proposed. However, many of them aLre disadvantageous in that amaunts of by-products are -formed, expensive compounds are used as the starting materials, and/or lengthy and compli-cated procedures are required to obtain the desired products.
Summary of the Invention ; It is an object of the present invention to pro-; , vide a one-step process for the highly selective preparation of indole and derivatives thereof by using inexpensive compounds as the starting materials.
An aspect of the invention is as follows:
A process for the preparation of an indole which comprises reacting an aniline of the general formula ~I) ~ R (I) where R represents a hydrogen atom, halogen atom, hydroxyl group, alkyi group or alkoxy group, with a 1,2-glycol selected from the group consisting of ethylene glycol, propylene glycol, 1,2-butanediol, 1,2~4-butanetriol, glycerol, 2,3-butanediol and diethylene glycol in the presence o~ a catalyst containing metallic copper and/or copper oxide, in the liquid phase at a temperature in the range of from 200C
to 500C, thereby forming the indole.
This reaction can be carried out both in the -3a-, ~ .
llS07z9 ll ll liquid phase and in the vapor phase. By way of example, the process of the present invention makes it possible to obtain indole by reacting aniline with ethylene glycol and to obtain 5-methylindole by reacting ~-toluidine with ethylene glycol.
Thus, the process of the present invention has a number of advantages. First, the anilines and 1,2-glycols which can be used as the starting materials are very in-expensive. Secondly, the preparation of indole or a deriv-ative thereof from the starting materials can be achieved in a single step. Thirdly, by-products are scarcely formed and a very high selectivity is attained, so that indole or a derivative thereof can be obtained in highly pure form.
I
i Detalled DescTiption of the Invention The aniline used in the process of the present invention is a compound of the general formula ` NH2 `
I ~ R (I) ¦l where R represents a hydrogen atom, halogen atom, hydroxyl group, alkyl group OT alkoxy group. Specific examples thereof are aniline, o-toluidine, _-toluidine, ~-toluidine, o-haloanilines, ~-haloanilines, m-haloanilines, o-aminophenol,¦
_-aminophenol, p-aminophenol, o-anisidine, _-anisidine, p-anisidine and the like.
The 1,2-glycol used in the process of the present invention is a member selected from the group consisting of ,' I
:` I
~5a~2~
`
ethylene glycol, propylene glycol, 1,2-butanediol, 1,2,4-butanetriol, glycerol, 2,3-butanediol, diethylene glycol and the like.
¦ The process of the present invention is carried out in the presence of a catalyst. The catalyst used therein is a copper-containing catalyst. That is, the ¦ catalyst contains metallic copper and/or copper oxide and, optionally, one or more other compounds.
More specifically, the catalysts which can be used in the process of the present invention are ones comprising metallic copper and/or copper oxide in such a form as powder, granules, masses, flakes, shaped pieces or the like; metallic copper ancL/or copper oxide supported on a carrier; a mixture of metallic copper and/or copper oxide and one or more other compounds; or such a mixture supported on a carrier.
I' The other compounds which can be used in combi-nation with metallic copper and/or copper oxide include the halides, nitrates, sulfates, carbonates, organic acid salts, oxides, hydroxides and the like of lithium, sodium, potassium, magnesium, calcium, strontium, barium, copper, I
silver, meTcuTy, zinc, aluminum, tin, iron3 cobalt, nickel, I
chromium, manganese, lead, molybdenum and the like; these metals in the elemental state; and the like.
The above-described catalysts can be prepared, for example, by the soaking method in which a carrieT is soaked in an aqueous solution of a water-soluble copper salt, dried and then subjected to thermal decomposition.
1 , 1, ; I
~ 5~ 9 Alternatively, they can also be prepared by the coprecipita-tion method. For example, an alkali is added to a stirred ¦ aqueous solution of copper nitrate, magnesium nitrate, j, manganese nitrate and the like to coprecipitate copper, magnesium, manganese and the like. The precipitate so formed is separated by filtration, washed, dried and then calcined. The metal salts should be used in such amounts as to give the above-defined composition. Preferably, the I precipitate is dried at room temperature for several to 24 l~ hours, at temperatures of from 100 to 200C for several hours, or at temperatures of from 350 to 550C for several hours. When dried at temperatures of from 100 to 250C, the precipitate is preferabl~ pelletized prior to calcination.
As the carrier on which the catalytic substance of the present invention (i.e., me~aliic copper and/or copper oxide or a mixture of metallic copper andjor copper oxide and one or more other compounds) is supported, any materials that arè in common use for supported catalysts can be used. However, diatomaceous earth, pumice, titania, silica-alumina, alumina, magnesia, silica gel, activated carbon, activated clay, asbestos and the like are used in typical cases.
I Supported catalysts can be prepared by supporting the above-described catalytic substance on these carriers ¦¦ according to any conventional techniques. For example, they are prepared by soaking a carrier in an aqueous solution of a copper salt and, if necessary, other metal salts, adding sodium hydroxide thereto with stirring, and then drying the ll l :
72~
carrier until the water included therein is evaporated completely. No particular limitation is placed on the amount f catalytic substance supported on the carrier. Usually, depending on the type of carrier used, any suitable amount (for example, from 1 to 50%) of catalytic substance may be supported thereon.
Prior to the start of the reaction, the catalyst is usually subjected to a reduction treatment according to any conventional procedure. This is accomplished, for example, by heating the catalyst bed slowly with a mixture of hydrogen gas and nitrogen gas flowing therethrough and then keeping it at a temperature of from 200 to 300C for several hours.
~ lthough the process of the present invention can be carried out in the vapor phase, the licluid phase or a mixed vapor-liquid phase, it is usually carried out in the vapor phase~ Where the process of the present invention is carried out in thè vapor phase, a fixed-bed, fluidized-bed or moving-bed reactor can be used to effect the reaction by heating the vapors of an aniline and a 1,2-glycol in the presence of a catalyst. In this case, various inert gaseous substances may coexist as diluents for the vapors of the starting materials. The useful inert gaseous substances include, for example, nitrogen gas, carbon dioxide gas, water vapor, and the vapors of compounds that are inert to this reaction. Moreover~ hydrogen gas or a hydrogen-contain-ing gas may be used as a diluent.
The use of hydrogen gas or a hydrogen-containing Ii , l - 7 -I
~ ~ 5i~72~
., .
gas is especially suitable for the purpose of maintaining I the activity of the catalyst.
j Similarly, owing to its ability to suppress the decomposition of the 1,2-glycol over the catalyst, the use of water vapor is suitable for the purpose of maintaining the activity of the catalyst and enhancing the yield of the I desired product.
- l The amounts of aniline and 1,2-glycol fed to the reactor should be such that from 0.01 to 5 moles and prefer-ably from 0.05 to 2 moles of the 1,2-glycol is provided for each mole of the aniline. I:E the amounts are outside this range, a reduction in yield will be caused and/or large amounts of by-products will be formed. These starting materials are fed, after being vaporized in advance or directly in liquid form, to the reactor at a liquid space ` velocity o~ from 0.01 to 5 liters/liter of the catalyst/hour.
; The process of the present invention is carried ~` ~ out at a reaction temperature in the range of from 200 to 600C and preferably from 250 to 500C. If the reaction temperature is lower than 200C, the reaction can hardly proceed, while if it is higher than 600C, undesirably large amounts of by-produc*s will be formed.
The reaction pressure may be superatmospheric, atmospheric or subatmospheric.
Where the process of the present invention is ¦ carried out in the liquid phase or a mixed vapor-liquid phase, the reaction is effected by heating a mixture of an l aniline and a 1,2-glycol in the presence of at least one .1, . . ;
, ~15~ 9 Il , " ~
¦l member selected from the above-described catalysts. In ~I this case, various inert gaseous substances and/or solvents ¦ may coexist as diluents -for the starting materials. The ¦ useful inert gaseous substances include, for example, nitrogen gas, carbon dioxide gas, water vapor and the vapors of compounds that are inert to this reaction. The useful solvents include, for example, benzene, toluene, xylene, methanol, ethanol, isopropanol, dioxane, dimethylformamide, ~ dimethyl sulfoxide, pyridine, N-methylpyrrolidone, tri-,l methylamine, diethylamine, triethylamine, tripropylamine, j tTibutylamine, diphenylamine, triphenylamine and other I organic solvents.
I IIn the case of liquid-phase reaction, the process I ~of the present invention can be carried out in a fixed-bed7 fluidized-bed or moving-bed reactor or in a rotary or con-tinuous reactor for liquid-phase reactions. However, no particular limitation is placed on the type of reactor used.
The amounts of aniline and 1,2-glycol used as the starting materials for this reaction should be such that from 0.05 to 5 molès and preferably from 0.1 to 2 moles of the 1,2-glycol is provlded for each mole of the aniline.
~ No particular limitation is placed on the amount ; Ijof catalyst used for this reaction. However, the catalyst ¦ is generally used in an amount of from 0.01 to 20 g and preferably from 0.1 to lO g of the active component thereof per mole of the aniline used as one of the starting materials.
The reaction temperature should be in the range of from 200 to 500C and preferably from 250 to 400C. If ll l ,1 9 .1 i.
.
the reaction temperature is low0r than 200Cs the reaction can hardly proceed9 while if it is higher than 500C, undesirably large amounts of by-products will be formed.
The reaction pressure may be superatmospheric or , atmospheric.
In various embodiments of the present invention, indole or a derivative thereof can readily be obtained in pure form by isolating it from the reaction product accord-ing to any conventional technique such as distillation.
The present invention is further illustrated by the following examples.
Example 1 Il ~
A 25-mm flow reactor made of Pyrex glass was packed with 50 m~ of copper oxide in granular form. The front end of this Teactor was connected with a feed inlet pipe and a ,-` gas inlet pipe to form a feed vaporization zone, while the rear end thereof was connected with a receiver by way of an air-cooling zone. After the copper oxide within the reactor was reduced by passing therethrough hydrogen gas at 200C
for 1 hour, the internal temperature of the reactor was kept at 300C. Then, a mixture consisting of 93.1 g ~1 mole) il of aniline and 6.2 g (0.1 mole) of ethylene glycol was introduced thereinto through the feed lnlet pipe at a liquid space velocity of 0.1 litsr/liter of the catalyst/hour. At the same time, nitrogen gas at atmospheric pressure was passed therethrough in an amount of 10 moles per mole of ! the aniline used as one of the starting materials. The , ^~c/e /J~J~r,~
, ~15~
! reaction product withdrawn from the reactor, condensed and -i collected in the receiver was analyzed by gas chromatography.
Thus, it was found that a yield of 8.1 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 76.7% and 90.3%, respectively. This indicates that by-products were formed in very small amounts.
Example 2 Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in Example 1 except that a catalyst comprising 20% by weight of copper oxide supported on diatomaceous earth was used in place of the unsupported copper oxide catalyst. As a result, a yield of 7.5 g of indole was obtained. The conversion and I selectivity based on the ethylene glycol were 73.2% and I 87.6%, respectively.
jl Example 3 I!
Using a reactor similar to that of Example 1, li reaction was carried out in the same manner as described in il Example 1 except that a catalyst comprising 10% by weight of copper oxide supported on granular activated carbon was I used in place of the unsupported copper oxide catalyst. I
¦ As a result, a yield of 8.5 g of indole was obtained. The con~ersion and selectivity based on the ethylene glycol were 78.1% and 87.2%, respectively.
, ' I 1~5~7~9 Example 4 Using a reactor similar to that of Example 1, ¦ reaction was carried out in the same manner as described in '~
Example l except that a CuO-ZnO catalyst ~containing 10 Il mole % of ZnO) was used in place of the unsupported copper ¦¦ oxide catalyst. As a result, a yield of 8.6 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 80.3% and 91.2%, respectively.
,1 , Example 5 ,i 1~ Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in ¦ Example 1 except that a CuO-Cr2O3 catalyst (containing 20 mole % of Cr2O3) was used in place of the unsupported copper oxide catalyst. As a result, a yie-d of 7.8 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 80.5% and 82.8%, respectively.
~ I
Example 6 ' Using a reactor similar to that of Example 1, ,il reaction was carried out in the same manner as described in Example 1 except that a CuO-MgO-MnO2 catalyst (containing 10 mole % of MgO and 10 mole % of MnO2) was used in place Il of the unsupported copper oxide catalyst. As a result, a I yield of 9.2 g of indole was obtained. The con~ersion and ,, selectivity based on the ethylene glycol were 85.2% and 1 92.1%, respectively.
:1 !
.
1, , ~, Si~72~
~i :
Example 7 Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in Example 1 except that the Raney copper catalyst which had been expanded and washed with water was used in place of the unsupported copper oxide catalyst. As a result, a yield of 6.4 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 63.6% and 86.3%, respectively.
Example 8 Reaction was carried out in the same manner as described in Example 1 except that 107 g ~1 mole) of ~-¦ toluidine was used in place of the aniline. As a result,a yield o 2.3 g oE 5-methylindole was obtained. The conversion and selectivity based on the ethylene glycol were 24.2% and 73.5%, respectively.
. .
Example 9 ~~ Reaction was carried out in the same manner as I ,1 described in Example 1 except that 123 g ~1 mole) of ,1 , ~-anisidine was used in place of the aniline. As a result, a yield of 1.5 g of 5-methoxyindole was obtained. The conversion and selectivity based on the ethylene glycol were 14.6% and 70.3%, respectively.
~I ;
.i , ~ - 13 -.
1 ,
~ , Background of the Inven~ion i i 1) Field of the Invention This invention relates to a novel process for the preparation of indole and derivatives thereof by reacting ~, an aniline with a 1,2-glycol in the presence of a copper-containing catalyst.
.j 2) Description of the PrioT Art i ll In the prio~ art, indole derivatives have long been prepared by the well-known Fischer indole synthesis in which phenylhydrazine is reacted with a compound having an aldehyde group. If the aldehyde compo~und is other than acetaldehyde, the aforesaid Fischer indole synthesis can be I , , .
~L~5~7 ' applied to obtain indole derivatives in good yield. However~
if the aldehyde compound is acetaldehyde, no reaction that yields indole has been believed to take place. In order to overcome this disadvantage, there has recently been proposed an improved process which comprises reacting phenylhydrazine with acetaldehyde at an elevated temperature of from 300 to 400C in the presence of an alumina catalyst (Japanese Patent Laid-Open No. 76864/'73).
This process surely permits the reaction to pro-ceed and brings about the formation of indole J but fails to give a satisfactory yield. Moreover, it is greatly dis-advantageous in that the catalyst has so short a life as to become totally inacti~e after 0.5-1 hour's use.
Indole can also be prepared by another process which comprises reacting o-toluidine with -formic acid to form o-methyl-N-formylaniline and then fusing it together with potassium hydroxide. However, it is usually impossible to selectively prèpare o-toluidine that is used as the starting material in this process. That is, the ~-isomer is always formed in an amount equal to or greater than that of the o-isomer. Thus, treatment of the isomer formed as a by-product poses a serious problem in the case of indus-trial production. Moreover, the handling of solids as in alkali fusion is troublesome. For these reasons, the aforesaîd process cannot be regarded as suitable for indus-trial purposes.
Furthermore~ a number of attempts have been made to synthesize indole from N~ -hydroxyethylamine, but none , , ,, .
72~
o them are satisfactory from an industrial point of view.
For example, a process which comprises effecting the ; reaction at 30UC in the presence of an aluminosilicate catalyst [Zhur. Obschue. Khim., Vol. 24, pp. 671-678 (1954)]
gives only a very low yield of indole. A process which comprises heating the reactant together with a molten mixed salt consisting mainly of zinc chloride (Japanese Patent Laid-Open No. 57968/'73) can give a fairly high yield of indole. However, this process has the disadvantage of requiring a complicated procedure, which makes it unsuitable ~I for industrial purposes.
l~ ~s described above, a number of processes for the ¦ synthesis of indole and derivatives thereof have been ; proposed. However, many of them aLre disadvantageous in that amaunts of by-products are -formed, expensive compounds are used as the starting materials, and/or lengthy and compli-cated procedures are required to obtain the desired products.
Summary of the Invention ; It is an object of the present invention to pro-; , vide a one-step process for the highly selective preparation of indole and derivatives thereof by using inexpensive compounds as the starting materials.
An aspect of the invention is as follows:
A process for the preparation of an indole which comprises reacting an aniline of the general formula ~I) ~ R (I) where R represents a hydrogen atom, halogen atom, hydroxyl group, alkyi group or alkoxy group, with a 1,2-glycol selected from the group consisting of ethylene glycol, propylene glycol, 1,2-butanediol, 1,2~4-butanetriol, glycerol, 2,3-butanediol and diethylene glycol in the presence o~ a catalyst containing metallic copper and/or copper oxide, in the liquid phase at a temperature in the range of from 200C
to 500C, thereby forming the indole.
This reaction can be carried out both in the -3a-, ~ .
llS07z9 ll ll liquid phase and in the vapor phase. By way of example, the process of the present invention makes it possible to obtain indole by reacting aniline with ethylene glycol and to obtain 5-methylindole by reacting ~-toluidine with ethylene glycol.
Thus, the process of the present invention has a number of advantages. First, the anilines and 1,2-glycols which can be used as the starting materials are very in-expensive. Secondly, the preparation of indole or a deriv-ative thereof from the starting materials can be achieved in a single step. Thirdly, by-products are scarcely formed and a very high selectivity is attained, so that indole or a derivative thereof can be obtained in highly pure form.
I
i Detalled DescTiption of the Invention The aniline used in the process of the present invention is a compound of the general formula ` NH2 `
I ~ R (I) ¦l where R represents a hydrogen atom, halogen atom, hydroxyl group, alkyl group OT alkoxy group. Specific examples thereof are aniline, o-toluidine, _-toluidine, ~-toluidine, o-haloanilines, ~-haloanilines, m-haloanilines, o-aminophenol,¦
_-aminophenol, p-aminophenol, o-anisidine, _-anisidine, p-anisidine and the like.
The 1,2-glycol used in the process of the present invention is a member selected from the group consisting of ,' I
:` I
~5a~2~
`
ethylene glycol, propylene glycol, 1,2-butanediol, 1,2,4-butanetriol, glycerol, 2,3-butanediol, diethylene glycol and the like.
¦ The process of the present invention is carried out in the presence of a catalyst. The catalyst used therein is a copper-containing catalyst. That is, the ¦ catalyst contains metallic copper and/or copper oxide and, optionally, one or more other compounds.
More specifically, the catalysts which can be used in the process of the present invention are ones comprising metallic copper and/or copper oxide in such a form as powder, granules, masses, flakes, shaped pieces or the like; metallic copper ancL/or copper oxide supported on a carrier; a mixture of metallic copper and/or copper oxide and one or more other compounds; or such a mixture supported on a carrier.
I' The other compounds which can be used in combi-nation with metallic copper and/or copper oxide include the halides, nitrates, sulfates, carbonates, organic acid salts, oxides, hydroxides and the like of lithium, sodium, potassium, magnesium, calcium, strontium, barium, copper, I
silver, meTcuTy, zinc, aluminum, tin, iron3 cobalt, nickel, I
chromium, manganese, lead, molybdenum and the like; these metals in the elemental state; and the like.
The above-described catalysts can be prepared, for example, by the soaking method in which a carrieT is soaked in an aqueous solution of a water-soluble copper salt, dried and then subjected to thermal decomposition.
1 , 1, ; I
~ 5~ 9 Alternatively, they can also be prepared by the coprecipita-tion method. For example, an alkali is added to a stirred ¦ aqueous solution of copper nitrate, magnesium nitrate, j, manganese nitrate and the like to coprecipitate copper, magnesium, manganese and the like. The precipitate so formed is separated by filtration, washed, dried and then calcined. The metal salts should be used in such amounts as to give the above-defined composition. Preferably, the I precipitate is dried at room temperature for several to 24 l~ hours, at temperatures of from 100 to 200C for several hours, or at temperatures of from 350 to 550C for several hours. When dried at temperatures of from 100 to 250C, the precipitate is preferabl~ pelletized prior to calcination.
As the carrier on which the catalytic substance of the present invention (i.e., me~aliic copper and/or copper oxide or a mixture of metallic copper andjor copper oxide and one or more other compounds) is supported, any materials that arè in common use for supported catalysts can be used. However, diatomaceous earth, pumice, titania, silica-alumina, alumina, magnesia, silica gel, activated carbon, activated clay, asbestos and the like are used in typical cases.
I Supported catalysts can be prepared by supporting the above-described catalytic substance on these carriers ¦¦ according to any conventional techniques. For example, they are prepared by soaking a carrier in an aqueous solution of a copper salt and, if necessary, other metal salts, adding sodium hydroxide thereto with stirring, and then drying the ll l :
72~
carrier until the water included therein is evaporated completely. No particular limitation is placed on the amount f catalytic substance supported on the carrier. Usually, depending on the type of carrier used, any suitable amount (for example, from 1 to 50%) of catalytic substance may be supported thereon.
Prior to the start of the reaction, the catalyst is usually subjected to a reduction treatment according to any conventional procedure. This is accomplished, for example, by heating the catalyst bed slowly with a mixture of hydrogen gas and nitrogen gas flowing therethrough and then keeping it at a temperature of from 200 to 300C for several hours.
~ lthough the process of the present invention can be carried out in the vapor phase, the licluid phase or a mixed vapor-liquid phase, it is usually carried out in the vapor phase~ Where the process of the present invention is carried out in thè vapor phase, a fixed-bed, fluidized-bed or moving-bed reactor can be used to effect the reaction by heating the vapors of an aniline and a 1,2-glycol in the presence of a catalyst. In this case, various inert gaseous substances may coexist as diluents for the vapors of the starting materials. The useful inert gaseous substances include, for example, nitrogen gas, carbon dioxide gas, water vapor, and the vapors of compounds that are inert to this reaction. Moreover~ hydrogen gas or a hydrogen-contain-ing gas may be used as a diluent.
The use of hydrogen gas or a hydrogen-containing Ii , l - 7 -I
~ ~ 5i~72~
., .
gas is especially suitable for the purpose of maintaining I the activity of the catalyst.
j Similarly, owing to its ability to suppress the decomposition of the 1,2-glycol over the catalyst, the use of water vapor is suitable for the purpose of maintaining the activity of the catalyst and enhancing the yield of the I desired product.
- l The amounts of aniline and 1,2-glycol fed to the reactor should be such that from 0.01 to 5 moles and prefer-ably from 0.05 to 2 moles of the 1,2-glycol is provided for each mole of the aniline. I:E the amounts are outside this range, a reduction in yield will be caused and/or large amounts of by-products will be formed. These starting materials are fed, after being vaporized in advance or directly in liquid form, to the reactor at a liquid space ` velocity o~ from 0.01 to 5 liters/liter of the catalyst/hour.
; The process of the present invention is carried ~` ~ out at a reaction temperature in the range of from 200 to 600C and preferably from 250 to 500C. If the reaction temperature is lower than 200C, the reaction can hardly proceed, while if it is higher than 600C, undesirably large amounts of by-produc*s will be formed.
The reaction pressure may be superatmospheric, atmospheric or subatmospheric.
Where the process of the present invention is ¦ carried out in the liquid phase or a mixed vapor-liquid phase, the reaction is effected by heating a mixture of an l aniline and a 1,2-glycol in the presence of at least one .1, . . ;
, ~15~ 9 Il , " ~
¦l member selected from the above-described catalysts. In ~I this case, various inert gaseous substances and/or solvents ¦ may coexist as diluents -for the starting materials. The ¦ useful inert gaseous substances include, for example, nitrogen gas, carbon dioxide gas, water vapor and the vapors of compounds that are inert to this reaction. The useful solvents include, for example, benzene, toluene, xylene, methanol, ethanol, isopropanol, dioxane, dimethylformamide, ~ dimethyl sulfoxide, pyridine, N-methylpyrrolidone, tri-,l methylamine, diethylamine, triethylamine, tripropylamine, j tTibutylamine, diphenylamine, triphenylamine and other I organic solvents.
I IIn the case of liquid-phase reaction, the process I ~of the present invention can be carried out in a fixed-bed7 fluidized-bed or moving-bed reactor or in a rotary or con-tinuous reactor for liquid-phase reactions. However, no particular limitation is placed on the type of reactor used.
The amounts of aniline and 1,2-glycol used as the starting materials for this reaction should be such that from 0.05 to 5 molès and preferably from 0.1 to 2 moles of the 1,2-glycol is provlded for each mole of the aniline.
~ No particular limitation is placed on the amount ; Ijof catalyst used for this reaction. However, the catalyst ¦ is generally used in an amount of from 0.01 to 20 g and preferably from 0.1 to lO g of the active component thereof per mole of the aniline used as one of the starting materials.
The reaction temperature should be in the range of from 200 to 500C and preferably from 250 to 400C. If ll l ,1 9 .1 i.
.
the reaction temperature is low0r than 200Cs the reaction can hardly proceed9 while if it is higher than 500C, undesirably large amounts of by-products will be formed.
The reaction pressure may be superatmospheric or , atmospheric.
In various embodiments of the present invention, indole or a derivative thereof can readily be obtained in pure form by isolating it from the reaction product accord-ing to any conventional technique such as distillation.
The present invention is further illustrated by the following examples.
Example 1 Il ~
A 25-mm flow reactor made of Pyrex glass was packed with 50 m~ of copper oxide in granular form. The front end of this Teactor was connected with a feed inlet pipe and a ,-` gas inlet pipe to form a feed vaporization zone, while the rear end thereof was connected with a receiver by way of an air-cooling zone. After the copper oxide within the reactor was reduced by passing therethrough hydrogen gas at 200C
for 1 hour, the internal temperature of the reactor was kept at 300C. Then, a mixture consisting of 93.1 g ~1 mole) il of aniline and 6.2 g (0.1 mole) of ethylene glycol was introduced thereinto through the feed lnlet pipe at a liquid space velocity of 0.1 litsr/liter of the catalyst/hour. At the same time, nitrogen gas at atmospheric pressure was passed therethrough in an amount of 10 moles per mole of ! the aniline used as one of the starting materials. The , ^~c/e /J~J~r,~
, ~15~
! reaction product withdrawn from the reactor, condensed and -i collected in the receiver was analyzed by gas chromatography.
Thus, it was found that a yield of 8.1 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 76.7% and 90.3%, respectively. This indicates that by-products were formed in very small amounts.
Example 2 Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in Example 1 except that a catalyst comprising 20% by weight of copper oxide supported on diatomaceous earth was used in place of the unsupported copper oxide catalyst. As a result, a yield of 7.5 g of indole was obtained. The conversion and I selectivity based on the ethylene glycol were 73.2% and I 87.6%, respectively.
jl Example 3 I!
Using a reactor similar to that of Example 1, li reaction was carried out in the same manner as described in il Example 1 except that a catalyst comprising 10% by weight of copper oxide supported on granular activated carbon was I used in place of the unsupported copper oxide catalyst. I
¦ As a result, a yield of 8.5 g of indole was obtained. The con~ersion and selectivity based on the ethylene glycol were 78.1% and 87.2%, respectively.
, ' I 1~5~7~9 Example 4 Using a reactor similar to that of Example 1, ¦ reaction was carried out in the same manner as described in '~
Example l except that a CuO-ZnO catalyst ~containing 10 Il mole % of ZnO) was used in place of the unsupported copper ¦¦ oxide catalyst. As a result, a yield of 8.6 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 80.3% and 91.2%, respectively.
,1 , Example 5 ,i 1~ Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in ¦ Example 1 except that a CuO-Cr2O3 catalyst (containing 20 mole % of Cr2O3) was used in place of the unsupported copper oxide catalyst. As a result, a yie-d of 7.8 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 80.5% and 82.8%, respectively.
~ I
Example 6 ' Using a reactor similar to that of Example 1, ,il reaction was carried out in the same manner as described in Example 1 except that a CuO-MgO-MnO2 catalyst (containing 10 mole % of MgO and 10 mole % of MnO2) was used in place Il of the unsupported copper oxide catalyst. As a result, a I yield of 9.2 g of indole was obtained. The con~ersion and ,, selectivity based on the ethylene glycol were 85.2% and 1 92.1%, respectively.
:1 !
.
1, , ~, Si~72~
~i :
Example 7 Using a reactor similar to that of Example 1, reaction was carried out in the same manner as described in Example 1 except that the Raney copper catalyst which had been expanded and washed with water was used in place of the unsupported copper oxide catalyst. As a result, a yield of 6.4 g of indole was obtained. The conversion and selectivity based on the ethylene glycol were 63.6% and 86.3%, respectively.
Example 8 Reaction was carried out in the same manner as described in Example 1 except that 107 g ~1 mole) of ~-¦ toluidine was used in place of the aniline. As a result,a yield o 2.3 g oE 5-methylindole was obtained. The conversion and selectivity based on the ethylene glycol were 24.2% and 73.5%, respectively.
. .
Example 9 ~~ Reaction was carried out in the same manner as I ,1 described in Example 1 except that 123 g ~1 mole) of ,1 , ~-anisidine was used in place of the aniline. As a result, a yield of 1.5 g of 5-methoxyindole was obtained. The conversion and selectivity based on the ethylene glycol were 14.6% and 70.3%, respectively.
~I ;
.i , ~ - 13 -.
1 ,
Claims (12)
1. A process for the preparation of an indole which comprises reacting an aniline of the general formula (I) (I) where R represents a hydrogen atom, halogen atom, hydroxyl group, alkyl group or alkoxy group, with a 1,2-glycol selected from the group consisting of ethylene glycol, propylene glycol, 1,2-butanediol, 1,2,4-butanetriol, glycerol, 2,3-butanediol and diethylene glycol in the presence of a catalyst containing metallic copper and/or copper oxide, in the liquid phase at a temperature in the range of from 200°C
to 500°C, thereby forming the indole.
to 500°C, thereby forming the indole.
2. A process as claimed in claim 1 wherein the catalyst further contains at least one compound selected from the group consisting of sulfates, carbonates, oxides and hydroxides of magnesium, calcium, strontium, barium, silver, zinc, aluminum, tin, iron, cobalt, nickel, chromium, manganese, titanium, lead, molybdenum and silicon.
3. A process as claimed in claim 1 wherein the catalyst contains copper oxide and at least one oxide of silicon, zinc, manganese, magnesium, aluminum, chromium, titanium or iron.
4. A process as claimed in claim 3 wherein the catalyst contains copper oxide in an amount of from 10 to 80% based on the weight of the catalyst.
5. A process as claimed in claim 1 wherein the catalyst contains copper oxide, silicon oxide and at least one oxide of zinc, manganese, magnesium, aluminum or chromium.
6. A process as claimed in claim 5 wherein the catalyst contains copper oxide in an amount of from 10 to 70% based on the weight of the catalyst and silicon oxide in an amount of from 10 to 70% based on the weight of the catalyst.
7. A process as claimed in claim 5 wherein the catalyst is a mixed oxide catalyst selected from CuO-SiO2-MgO, CuO-SiO2-ZnO, CuO-SiO2-ZnO-MnO2 or Cu-SiO2-ZnO-Cr2O3.
8. A process as claimed in claim 1 wherein said aniline is selected from the group consisting of o-, m- or p-toluidine, o-, m- or p-haloanilines, o-, m- or p-aminophenol and o-, m- or p-anisidine.
9. A process as claimed in claim 1 wherein the saction is carried out in an atmosphere containing hydrogen gas.
10. A process as claimed in claim 1 wherein the reaction is carried out in the presence of water or water vapor.
11. A process as claimed in claim 1 wherein the reaction is carried out at a pressure of less than 150 kg/cm2G.
12. A process as claimed in claim 1 wherein the amount of the 1,2-glycol is 0.05 to 5 moles per each mole of the aniline.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000375821A CA1150729A (en) | 1981-04-21 | 1981-04-21 | Process for the preparation of indole and derivatives thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000375821A CA1150729A (en) | 1981-04-21 | 1981-04-21 | Process for the preparation of indole and derivatives thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1150729A true CA1150729A (en) | 1983-07-26 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000375821A Expired CA1150729A (en) | 1981-04-21 | 1981-04-21 | Process for the preparation of indole and derivatives thereof |
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| CA (1) | CA1150729A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620857A (en) * | 2021-09-07 | 2021-11-09 | 太原理工大学 | Method for synthesizing melatonin intermediate by taking p-methoxyaniline as raw material |
| CN113861098A (en) * | 2021-09-07 | 2021-12-31 | 太原理工大学 | Synthetic method of indole derivative |
-
1981
- 1981-04-21 CA CA000375821A patent/CA1150729A/en not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113620857A (en) * | 2021-09-07 | 2021-11-09 | 太原理工大学 | Method for synthesizing melatonin intermediate by taking p-methoxyaniline as raw material |
| CN113861098A (en) * | 2021-09-07 | 2021-12-31 | 太原理工大学 | Synthetic method of indole derivative |
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