CA1127163A - Process for the production of indoles - Google Patents
Process for the production of indolesInfo
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- CA1127163A CA1127163A CA331,549A CA331549A CA1127163A CA 1127163 A CA1127163 A CA 1127163A CA 331549 A CA331549 A CA 331549A CA 1127163 A CA1127163 A CA 1127163A
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Abstract
ABSTRACT OF THE DISCLOSURE:
Indoles of the formula:
(wherein R is hydrogen, halogen, 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C alkylsulfonyl, or 2-10C dialkylamino;
and n is an integer from 1 to 3) are prepared by reductively cyclizing a compound of the formula:
Indoles of the formula:
(wherein R is hydrogen, halogen, 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C alkylsulfonyl, or 2-10C dialkylamino;
and n is an integer from 1 to 3) are prepared by reductively cyclizing a compound of the formula:
Description
11;~7~63 1 The present invention relates to a process for the production of indoles unsubstituted in the pyrrole ring.
As is well known, indoles are broadly used in the field of dyestuffs, perfumes, or medicinals and especially useful as starting materials for preparing indole alkaloids. Many reports for preparing indoles have heretobefore appeared from practical and/or academic points of view but there are comparatively few reports on indoles having an unsubstituted pyrrole ring.
Synthetic process for preparing indole being unsubstituted in the pyrrole ring published prior to 1970 are illustrated in the Reissert process [A. Reissert:
Chem. Ber., 30, 1030 (1897)] and Nenitzescu process [Nenitzescu, Chem. Berg., 58, 1063 (1927)]. Both processes use a substituted o-nitrotoluene as a starting material, but its availability or synthesis is accompanied with considerable difficulty, depending upon the sort and ~ 'I
position of the substituent.
The Leimgruber process [W. Leimgruber et al: 3rd International Congress of Heterocyclic Chemistry, Sendai, p. 462 (1971)] was reported as an improvement over ~he Reissert process. This process consists of reacting a ~ substituted o-nitrotoluene with dimethylformamide dimethyl - acetal, however, it is accompanied with low availability of the starting material and dimethylformamide dimethyl acetal. As a result, this improvement process is far from simple to carry out.
Recently Nakazaki et al reported a modified Fischer process which comprises contacting acetaldehyde phenylhydrazone with a catalyst such as aluminum oxide or 1 aluminum chloride [M. Nakazaki et al: J. Org. Chem., 41, 1877 (1976)]. However this process has some limitations such as, requiring a high reaction temperature and special installations.
Furthermore, Bakke [J. Rakke et al: Acta. Chem.
Scand. B28, 393 (1974)] and Gassman IP.G. Gassman: J. Am.
Chem. Soc., 96, 5495 (1974)] disclose a synthetic process for making indoles unsubstituted in the pyrrole ring.
However, the former has defects including use of not readily available o-nitrotoluene substituted in the benzene ring, a requirement of high reaction temperature in the final stage, and low yield. The latter has advantages such as workability at low temperature and applicability of a monosubstituted aniline as the starting material, but also has disadvantages such as difficulty in preparing methylthioacetaldehyde or its acetal, a reagent, and requirement of desulfurization in the final step.
With respect to a mass-producible process, Mitsui Toatsu Chem. Inc. reported that b~zofuran was heated with ammonia over zeolite containing a metal ion at 200-400 degrees C to give indole in 10 to 60~ conversion of benzofuran and 30 to 80% selectivity of indole ~Japanese Patent Unexamined Publication No. 59855/1976~. However this process has unsatisfactory limitations such as requirement of high reaction temperature and low yield.
As a result of extensive research, the present inventors have now found a synthetic process for an indus-trially efficient synthesis of such indoles unsubstituted in the pyrrole ring by very simple procedures from readily llZ7~63 1 available or easily producible starting materials.
The present invention is directed to a process for the production of indoles of the formula:
(Rl ~ ~ (I) (wherein R is hydrogen, halogen, 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C alkylsulfonyl, or 2-lOC dialkylamino;
' and n is an integer from l to 3).
which comprises reductively cyclizing a compound of the formula: O
. 11 (R)n ~ C~2H2X (II) ~ (wherein X is halogen; R and n have the same significance as given earlier).
A preferred embodiment of this invention is a process for preparing a compound of the formula:
(R )n ~ (I~) H
(wherein R is hydrogen, halogen, 1-3C alkyl, or 1-3C alkoxy;
and n is an integer of 1 to 2) which comprises reductively cyclizing a compound of the formula:
O
Il (R )n ~ C~2H2X (V~
(wherein X is halogen; R and n have the same significance as given earlier).
.
" llZ7~63 1 The starting compound (II) may be prepared, for example, by reacting a corresponding substituted or unsubstituted aniline with a halo-acetonitrile over boron trichloride preferably in the presence of aluminum chloride. This reaction is generally carried out in an inert solvent such as benzene, toluene, methylene chloride, dichloroethane, or tetrachloroethane.
Cyclization of the present invention is carried out by reducing the compound (II) with a metal hydride (e.g.
sodium borohydride, potassium borohydride, lithium aluminum hydride). This reduction is generally carried out in an enert solvent such as diethyl ether, dioxane, methanol, ethanol, or dimethylformamide. When the reduction is carried out at comparatively higher temperatures, for example, heating under refluxing, the final product can be obtained in a single step. When the reduction is carried out at a rather lower temperature, for example, room temperature, an intermediate of the following formula:
OH
As is well known, indoles are broadly used in the field of dyestuffs, perfumes, or medicinals and especially useful as starting materials for preparing indole alkaloids. Many reports for preparing indoles have heretobefore appeared from practical and/or academic points of view but there are comparatively few reports on indoles having an unsubstituted pyrrole ring.
Synthetic process for preparing indole being unsubstituted in the pyrrole ring published prior to 1970 are illustrated in the Reissert process [A. Reissert:
Chem. Ber., 30, 1030 (1897)] and Nenitzescu process [Nenitzescu, Chem. Berg., 58, 1063 (1927)]. Both processes use a substituted o-nitrotoluene as a starting material, but its availability or synthesis is accompanied with considerable difficulty, depending upon the sort and ~ 'I
position of the substituent.
The Leimgruber process [W. Leimgruber et al: 3rd International Congress of Heterocyclic Chemistry, Sendai, p. 462 (1971)] was reported as an improvement over ~he Reissert process. This process consists of reacting a ~ substituted o-nitrotoluene with dimethylformamide dimethyl - acetal, however, it is accompanied with low availability of the starting material and dimethylformamide dimethyl acetal. As a result, this improvement process is far from simple to carry out.
Recently Nakazaki et al reported a modified Fischer process which comprises contacting acetaldehyde phenylhydrazone with a catalyst such as aluminum oxide or 1 aluminum chloride [M. Nakazaki et al: J. Org. Chem., 41, 1877 (1976)]. However this process has some limitations such as, requiring a high reaction temperature and special installations.
Furthermore, Bakke [J. Rakke et al: Acta. Chem.
Scand. B28, 393 (1974)] and Gassman IP.G. Gassman: J. Am.
Chem. Soc., 96, 5495 (1974)] disclose a synthetic process for making indoles unsubstituted in the pyrrole ring.
However, the former has defects including use of not readily available o-nitrotoluene substituted in the benzene ring, a requirement of high reaction temperature in the final stage, and low yield. The latter has advantages such as workability at low temperature and applicability of a monosubstituted aniline as the starting material, but also has disadvantages such as difficulty in preparing methylthioacetaldehyde or its acetal, a reagent, and requirement of desulfurization in the final step.
With respect to a mass-producible process, Mitsui Toatsu Chem. Inc. reported that b~zofuran was heated with ammonia over zeolite containing a metal ion at 200-400 degrees C to give indole in 10 to 60~ conversion of benzofuran and 30 to 80% selectivity of indole ~Japanese Patent Unexamined Publication No. 59855/1976~. However this process has unsatisfactory limitations such as requirement of high reaction temperature and low yield.
As a result of extensive research, the present inventors have now found a synthetic process for an indus-trially efficient synthesis of such indoles unsubstituted in the pyrrole ring by very simple procedures from readily llZ7~63 1 available or easily producible starting materials.
The present invention is directed to a process for the production of indoles of the formula:
(Rl ~ ~ (I) (wherein R is hydrogen, halogen, 1-5C alkyl, 1-5C alkoxy, 1-5C alkylthio, 1-5C alkylsulfonyl, or 2-lOC dialkylamino;
' and n is an integer from l to 3).
which comprises reductively cyclizing a compound of the formula: O
. 11 (R)n ~ C~2H2X (II) ~ (wherein X is halogen; R and n have the same significance as given earlier).
A preferred embodiment of this invention is a process for preparing a compound of the formula:
(R )n ~ (I~) H
(wherein R is hydrogen, halogen, 1-3C alkyl, or 1-3C alkoxy;
and n is an integer of 1 to 2) which comprises reductively cyclizing a compound of the formula:
O
Il (R )n ~ C~2H2X (V~
(wherein X is halogen; R and n have the same significance as given earlier).
.
" llZ7~63 1 The starting compound (II) may be prepared, for example, by reacting a corresponding substituted or unsubstituted aniline with a halo-acetonitrile over boron trichloride preferably in the presence of aluminum chloride. This reaction is generally carried out in an inert solvent such as benzene, toluene, methylene chloride, dichloroethane, or tetrachloroethane.
Cyclization of the present invention is carried out by reducing the compound (II) with a metal hydride (e.g.
sodium borohydride, potassium borohydride, lithium aluminum hydride). This reduction is generally carried out in an enert solvent such as diethyl ether, dioxane, methanol, ethanol, or dimethylformamide. When the reduction is carried out at comparatively higher temperatures, for example, heating under refluxing, the final product can be obtained in a single step. When the reduction is carried out at a rather lower temperature, for example, room temperature, an intermediate of the following formula:
OH
2~ 1 ~ CH - cH2x ~R) ~ NH2 ~III) ~wherein R, X and n have the same significance as given earlier) is treated with a base such as alkali metal hydride (e.g.
sodium hydride, potassium hydride~ or alkali metal alkoxide (e.g. sodium methoxide, potassium ethoxide) to give the cyclized product (I).
The end product (I) is recovered from the reaction mixture by a conventional separating procedure such ~,fv , 1127~63 1 as evaporation, extraction, recrystallization, or like means.
Thus-obtained compounds (I) are useful as synthetic intermediates for a variety of useful materials such as dyestuffs, perfumes, or medicinals. For example, the compound (I : R=H; n=l) is useful as a synthetic intermediate for tryptamine and the compound (I : R=5-OH;
n=l) is useful as a synthetic intermediate for serotonin.
; As clearly shown above, the process of the present invention is industrially valuable and excellent as a synthetic process for making indoles with the following characteristics:
a) Reaction path is rather shorter;
b) Reaction conditions are very mild;
c) Ready availability of the starting materials and reagents;
d) No special installation is necessary;
e) Yield of the product is usually in the range of about 60 to 90%.
Presently-preferred and practical embodiments of the present invention are illustratively shown in the following examples.
Example_l To a solution of 2-amino-6-chloro- ~-chloro-acetophenone ~205 mg; 1 mmol) in a mixed medium of dioxane (5 ml) and water t0.5 ml) is added sodium borohydride (42 mg; 1.1 mmol) at room temperature, and the resultant mixture is refluxed for 2.5 hours. After finishing the reaction, the solvent is evaporated from the reaction mixture. The residue is mixed with water ~, llZ71~3 1 and shaken with methylene chloride. The methylene chloride layer is dried over anhydrous sodium sulfate and the solvent is evaporated. The residue is dissolved in benzene and chromatographed on a column of silica gel (1.6 g). The polar fractions are removed and the benzene eluates (10 - 15 ml) are concentrated to give 4-chloro-indole (136 mg) as an oily material. The product shows ; one spot in its chromatogram on a thin layer plate of silica gel, using methylene chloride as a developing solvent. Its picrate shows a melting point = 170-173C
(recrystallized from ethanol).
Example 2.
To a solution of 2-amino-4-methoxy-~-chloro-acetophenone (200 ml; 1 mmol) in dry ether (8 ml) is added lithium aluminum hydride (40 mg; 1.1 mmol) and the resultant mixtu~e is refluxed for 2 hours. After cooling, the reaction mixture is mixed with a small amount of wet ethyl acetate to decompose unreacted lithium aluminum hydride and with an amount of water.
The mixture is shaken with ether. The ethereal layer is washed with water, dried over anhydrous sodium sulfate, and the ether is evaporated. The residue is dissovled in a mixed medium of benzene and petroleum ether (1/1) and chromatographed on a column of silica gel, which is eluted with said mixed medium. The eluate (60 ml) is concentrated to dryness to give 6-methoxyindole (58 mg) as crystals melting at 87-88C.
Examples 3 - 13.
The reaction is carried out in a similar manner as described in Example 1, whereby indoles are ~lZ7163 obtained as shown in Table 1.
(R) ~ C-CH2Cl > (R) ~ ~
sodium hydride, potassium hydride~ or alkali metal alkoxide (e.g. sodium methoxide, potassium ethoxide) to give the cyclized product (I).
The end product (I) is recovered from the reaction mixture by a conventional separating procedure such ~,fv , 1127~63 1 as evaporation, extraction, recrystallization, or like means.
Thus-obtained compounds (I) are useful as synthetic intermediates for a variety of useful materials such as dyestuffs, perfumes, or medicinals. For example, the compound (I : R=H; n=l) is useful as a synthetic intermediate for tryptamine and the compound (I : R=5-OH;
n=l) is useful as a synthetic intermediate for serotonin.
; As clearly shown above, the process of the present invention is industrially valuable and excellent as a synthetic process for making indoles with the following characteristics:
a) Reaction path is rather shorter;
b) Reaction conditions are very mild;
c) Ready availability of the starting materials and reagents;
d) No special installation is necessary;
e) Yield of the product is usually in the range of about 60 to 90%.
Presently-preferred and practical embodiments of the present invention are illustratively shown in the following examples.
Example_l To a solution of 2-amino-6-chloro- ~-chloro-acetophenone ~205 mg; 1 mmol) in a mixed medium of dioxane (5 ml) and water t0.5 ml) is added sodium borohydride (42 mg; 1.1 mmol) at room temperature, and the resultant mixture is refluxed for 2.5 hours. After finishing the reaction, the solvent is evaporated from the reaction mixture. The residue is mixed with water ~, llZ71~3 1 and shaken with methylene chloride. The methylene chloride layer is dried over anhydrous sodium sulfate and the solvent is evaporated. The residue is dissolved in benzene and chromatographed on a column of silica gel (1.6 g). The polar fractions are removed and the benzene eluates (10 - 15 ml) are concentrated to give 4-chloro-indole (136 mg) as an oily material. The product shows ; one spot in its chromatogram on a thin layer plate of silica gel, using methylene chloride as a developing solvent. Its picrate shows a melting point = 170-173C
(recrystallized from ethanol).
Example 2.
To a solution of 2-amino-4-methoxy-~-chloro-acetophenone (200 ml; 1 mmol) in dry ether (8 ml) is added lithium aluminum hydride (40 mg; 1.1 mmol) and the resultant mixtu~e is refluxed for 2 hours. After cooling, the reaction mixture is mixed with a small amount of wet ethyl acetate to decompose unreacted lithium aluminum hydride and with an amount of water.
The mixture is shaken with ether. The ethereal layer is washed with water, dried over anhydrous sodium sulfate, and the ether is evaporated. The residue is dissovled in a mixed medium of benzene and petroleum ether (1/1) and chromatographed on a column of silica gel, which is eluted with said mixed medium. The eluate (60 ml) is concentrated to dryness to give 6-methoxyindole (58 mg) as crystals melting at 87-88C.
Examples 3 - 13.
The reaction is carried out in a similar manner as described in Example 1, whereby indoles are ~lZ7163 obtained as shown in Table 1.
(R) ~ C-CH2Cl > (R) ~ ~
3 2 6 ~ N 2 H
( II) (I) Table 1 :
Ex. II Reflux I yield M. p, (C) No. (R)n time (hr., (R)n (%) Found Reported 3 H 2 H 83 50-51 52-53 ) 45-Cl 5.55-Cl 69 67-68 71-72a) 54-Cl 5.56-Cl 79 85-86 89-89.5a) 63-Cl 6.07-Cl 64 57-58 57-58 ) 76-OCH3 1.04-OCH3 92 67-68 69.5 85-OCH3 1.05-OCH3 90 54-55 56-57 ) 94-OCH3 4.06-OCH3 34 87-88 88-90 ) 10 ~-OCH3 1.0~5-OCH3 54 158-159 154-155 ) 5-OCH3 `6-OCH3 11 4-F 5.0 6-F 72 75-76 74-76 ) 12 6-F 5.0 4-F 86 28-29 _ 13 (5-OCH3 1.0~5-OCH3- 84 117-118 119-120 )
( II) (I) Table 1 :
Ex. II Reflux I yield M. p, (C) No. (R)n time (hr., (R)n (%) Found Reported 3 H 2 H 83 50-51 52-53 ) 45-Cl 5.55-Cl 69 67-68 71-72a) 54-Cl 5.56-Cl 79 85-86 89-89.5a) 63-Cl 6.07-Cl 64 57-58 57-58 ) 76-OCH3 1.04-OCH3 92 67-68 69.5 85-OCH3 1.05-OCH3 90 54-55 56-57 ) 94-OCH3 4.06-OCH3 34 87-88 88-90 ) 10 ~-OCH3 1.0~5-OCH3 54 158-159 154-155 ) 5-OCH3 `6-OCH3 11 4-F 5.0 6-F 72 75-76 74-76 ) 12 6-F 5.0 4-F 86 28-29 _ 13 (5-OCH3 1.0~5-OCH3- 84 117-118 119-120 )
4-CH3 ~6-CH3 .
Ref. a) Leimgruber et al., shown before b) R~don et al. J. Chem. Soc., 3501 (1955) c) Allen et al. J. Org. Chem., 30, 2897 (1965) ~127163 .
l Example 14.
To a solution of 2-amino-3-chloro-~-chloro-acetophenone (410 mg; 2 mmol) in a mixed medium of methanol (10 ml) and water (0.5 ml) is added sodium borohydride (29 mg; 0.75 mmol), and the resultant mix-ture is stirred for 5 minutes. An amount of water is added thereto, and the resultant mixture is shaken with methylene chloride. The extract is washed with water, dried over anhydrous sodium sulfate, and concentrated to give 2-amino-3-chloro-~-hydroxphenethyl chloride (377 mg). Yield = 92%. This is applied on a thin layer plate, which is developed with methylene chloride to show one spot. m.p. 67 to 68C (recrystallized from petroleum ether).
Anal. Calcd. C8HgONC12: C, 46.62; H, 4.40: N, 6.80;
Cl, 34.41(%) Found: C, 46.74; H, 4.47; N, 6.88; Cl, 34.31(%).
IR: v 3 3570, 3470, 3380, 1618 cm max NMR, ~(CDC13): 3.85 and 3.88 (2H, ABX, JAB=11.2Hz, J =9.OHz, J -4.0Hæ, -CH -), 4.88(1H, q, -CH-), 6.63(lH, t, J=8Hz, C5-H), 6.99(lH, d , d, J=8Hz, J=2Hz, C5-H, C4-H or C6-H~, 7.25(lH, d, d, J=8Hz, J=2Hz, 6-H or 4-H).
Above-obtained compound (52 mg; 0.25 mmol) is added to a sodium methoxide solution (obtained by dissolv-ing metallic sodium (6.3 mg; 0.25 mmol) in absolute methanol (1.2 ml). The mixture is stirred at room temperature for 1 hour and the methanol is evaporated 11;~7163 .
1 under reduced pressure. An amount of water is added to the residue and the resultant mixture is shaken with methylene chloride. The methylene chloride extract is washed with water and dried over anhydrous sodium sulfate, and the solvent is evaporated to give 7-chloroindole (41 mg).
Yield=79%. Chromatogram on a thin layer plate, developed with methylene chloride, shows one spot, m.p. 57-58C.
Example 15.
To a solution of 2-amino-4-methoxy-~-chloro-acetophenone (200 mg; 1 mmol) in a mixed medium of methanol(6 ml) and water (0.3 ml) is added sodium borohydride (38 mg; 1 mmol), and the resultant solution is stirred for 5 minutes. The reaction mixture is mixed with a small amount of ammonium chloride and water in order and shaken with methylene chloride. The extract is whashed with water, dried, and evaporated to give 2-amino-4-methoxy-~-hydroxyphenethyl chloride (205 mg) as colorless crystals. The product is chromatographed on a thin layer plate, which is developed by methylene chloride to show one spot.
IR: ~CHC13 3570, 3470, 3380 cm max To a solution of above-obtained compound in dimethylformamide (4 ml) is added 50 ~ sodium hydride (in mineral oil) (50 mg; 1 mmol) under ice cooling, and the resultant mixture is stirred at room temperature.
The reaction mixture is mixed with ice and shaken with ether. The ether layer is separated, washed with water, dried, and concentrated under reduced pressure. The residue is suspended in petroleum ether and passed _ g .
: .
, , ~lZ71~i~
~ 1 through a column of ~ilica gel (1.5 g) to remove a non-polar fraction. The column is eluted with benzene (40 ml) and the eluate is concentrated, whereby 6-methoxyindole (69 mg) is obtained as crystals melting at 87-88C.
Ref. a) Leimgruber et al., shown before b) R~don et al. J. Chem. Soc., 3501 (1955) c) Allen et al. J. Org. Chem., 30, 2897 (1965) ~127163 .
l Example 14.
To a solution of 2-amino-3-chloro-~-chloro-acetophenone (410 mg; 2 mmol) in a mixed medium of methanol (10 ml) and water (0.5 ml) is added sodium borohydride (29 mg; 0.75 mmol), and the resultant mix-ture is stirred for 5 minutes. An amount of water is added thereto, and the resultant mixture is shaken with methylene chloride. The extract is washed with water, dried over anhydrous sodium sulfate, and concentrated to give 2-amino-3-chloro-~-hydroxphenethyl chloride (377 mg). Yield = 92%. This is applied on a thin layer plate, which is developed with methylene chloride to show one spot. m.p. 67 to 68C (recrystallized from petroleum ether).
Anal. Calcd. C8HgONC12: C, 46.62; H, 4.40: N, 6.80;
Cl, 34.41(%) Found: C, 46.74; H, 4.47; N, 6.88; Cl, 34.31(%).
IR: v 3 3570, 3470, 3380, 1618 cm max NMR, ~(CDC13): 3.85 and 3.88 (2H, ABX, JAB=11.2Hz, J =9.OHz, J -4.0Hæ, -CH -), 4.88(1H, q, -CH-), 6.63(lH, t, J=8Hz, C5-H), 6.99(lH, d , d, J=8Hz, J=2Hz, C5-H, C4-H or C6-H~, 7.25(lH, d, d, J=8Hz, J=2Hz, 6-H or 4-H).
Above-obtained compound (52 mg; 0.25 mmol) is added to a sodium methoxide solution (obtained by dissolv-ing metallic sodium (6.3 mg; 0.25 mmol) in absolute methanol (1.2 ml). The mixture is stirred at room temperature for 1 hour and the methanol is evaporated 11;~7163 .
1 under reduced pressure. An amount of water is added to the residue and the resultant mixture is shaken with methylene chloride. The methylene chloride extract is washed with water and dried over anhydrous sodium sulfate, and the solvent is evaporated to give 7-chloroindole (41 mg).
Yield=79%. Chromatogram on a thin layer plate, developed with methylene chloride, shows one spot, m.p. 57-58C.
Example 15.
To a solution of 2-amino-4-methoxy-~-chloro-acetophenone (200 mg; 1 mmol) in a mixed medium of methanol(6 ml) and water (0.3 ml) is added sodium borohydride (38 mg; 1 mmol), and the resultant solution is stirred for 5 minutes. The reaction mixture is mixed with a small amount of ammonium chloride and water in order and shaken with methylene chloride. The extract is whashed with water, dried, and evaporated to give 2-amino-4-methoxy-~-hydroxyphenethyl chloride (205 mg) as colorless crystals. The product is chromatographed on a thin layer plate, which is developed by methylene chloride to show one spot.
IR: ~CHC13 3570, 3470, 3380 cm max To a solution of above-obtained compound in dimethylformamide (4 ml) is added 50 ~ sodium hydride (in mineral oil) (50 mg; 1 mmol) under ice cooling, and the resultant mixture is stirred at room temperature.
The reaction mixture is mixed with ice and shaken with ether. The ether layer is separated, washed with water, dried, and concentrated under reduced pressure. The residue is suspended in petroleum ether and passed _ g .
: .
, , ~lZ71~i~
~ 1 through a column of ~ilica gel (1.5 g) to remove a non-polar fraction. The column is eluted with benzene (40 ml) and the eluate is concentrated, whereby 6-methoxyindole (69 mg) is obtained as crystals melting at 87-88C.
Claims (11)
OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of indoles of the formula:
wherein R is hydrogen, halogen, 1-5C alkyl or 1-5C alkoxy and n is an integer from 1 to 3, which comprises reductively cyclizing a compound of the formula:
wherein X is halogen; and R and n have the same significance as above, in an inert solvent medium.
wherein R is hydrogen, halogen, 1-5C alkyl or 1-5C alkoxy and n is an integer from 1 to 3, which comprises reductively cyclizing a compound of the formula:
wherein X is halogen; and R and n have the same significance as above, in an inert solvent medium.
2. A process according to claim 1, in which the reduction is carried out with a metal hydride.
3. A process according to claim 1, in which the reduction is carried out with heating under refluxing.
4. A process according to claim 2, in which the reduction is carried out with a metal hydride and the resultant product is treated with a base.
5. A process according to claim 3, in which the reduction is carried out with a metal hydride and the resultant product is treated with a base.
6. A process according to claim 4, in which the reduction is carried out at room temperature.
7. A process for preparing a compound of the formula:
wherein R1 is hydrogen, halogen, 1-3C alkyl, or 1-3C alkoxy and n is an integer of 1 or 2, which comprises reductively cyclyzing a compound of the formula:
wherein X is halogen; R1 and n have the same significance as above, in an inert solvent medium.
wherein R1 is hydrogen, halogen, 1-3C alkyl, or 1-3C alkoxy and n is an integer of 1 or 2, which comprises reductively cyclyzing a compound of the formula:
wherein X is halogen; R1 and n have the same significance as above, in an inert solvent medium.
8. A process according to claim 7, in which the reduction is carried out with a metal hydride.
9. A process according to claim 7 or 8, in which the reduction is carried out with heating under refluxing.
10. a process according to claim 7 or 8, in which the reduction is carried out with a metal hydride and the resultant product is treated with a base.
11. A process according to claim 7 or 8, in which the reduction is carried out at room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA331,549A CA1127163A (en) | 1979-07-10 | 1979-07-10 | Process for the production of indoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA331,549A CA1127163A (en) | 1979-07-10 | 1979-07-10 | Process for the production of indoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1127163A true CA1127163A (en) | 1982-07-06 |
Family
ID=4114658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA331,549A Expired CA1127163A (en) | 1979-07-10 | 1979-07-10 | Process for the production of indoles |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1127163A (en) |
-
1979
- 1979-07-10 CA CA331,549A patent/CA1127163A/en not_active Expired
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