CA2143499A1 - Process for the preparation of substituted phenylhydrazones - Google Patents
Process for the preparation of substituted phenylhydrazonesInfo
- Publication number
- CA2143499A1 CA2143499A1 CA002143499A CA2143499A CA2143499A1 CA 2143499 A1 CA2143499 A1 CA 2143499A1 CA 002143499 A CA002143499 A CA 002143499A CA 2143499 A CA2143499 A CA 2143499A CA 2143499 A1 CA2143499 A1 CA 2143499A1
- Authority
- CA
- Canada
- Prior art keywords
- process according
- substituted
- reaction
- preparation
- carried out
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/16—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of hydrazones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
- C07C251/74—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/76—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to an improved process for the preparation of substituted phenylhydrazones, starting from aniline derivatives and 1,3-dicarbonyl compounds, and to the use of the compounds thus prepared for the preparation of indoles.
Description
9 ~
De~cription The invention relates to a process for the preparation of substituted phenylhydrazones from a diazonium salt and a 1,3-dicarbonyl compound. Substituted phenylhydrazones are valuable intermediates in the preparation of substituted indoles.
These compounds have previously been prepared in a two-stage process starting from the correspo~ing aniline derivatives:
The aniline derivative was first converted into an anilinium hydrochloride which, after isolation, was treated with an aqueous solution of sodium nitrite.
Subsequently the diazonium salt obtained in this way was reacted in a water-soluble medium with the 1,3-dicarbonyl compound.
However, if the anilinium hydrochloride is employed for the preparation of the phenylhydrazones without isolating it beforehand in the manner indicated, the product is obtained in the form of a dark brown greasy mass which does not crystallize even after addi-tion of nonpolar solvents and cannot be worked up or separated off.
The object of the present invention was to discover a process in which the anilinium hydrochloride need not be prepared and isolated in a prior reaction but is prepared directly in situ and processed further.
Surprisingly it has now been found that the prior isolation can be avoided, while nevertheless obtaining crystalline products, if the reaction with the 1,3-dicarbonyl compound is carried out not, as previously, ina one-phase protic solvent but in a two-phase system with a water-insoluble solvent.
The invention thus relates to a process for the preparation of substituted phenylhydrazones from a diazonium salt and a 1,3-dicarbonyl compound in which the following steps are carried out in succession:
a~ reaction of an aniline derivative with hydrochloric 21~13~99 acid, b) addition of an aqueous solution of sodium nitrite, c) reaction with the 1,3-dicarbonyl compound in an inert solvent, characterized in that in step c) a water-immiscible sol~ent is used, preferably an aromatic hydrocarbon, especially toluene.
a) Preferred embodiments are: process for the prepara-tion of phenylhydrazones of the formula I
Ar NH--N--I (CH2)n COOH
COOR' in which Ar is a phenyl group which is unsubstituted or is substituted by one or more alkyl or alkoxy groups, preferably a phenyl group which is mono-substituted by Cl10-alkoxy Rl is a Cl-C8-al~yl group, preferably Cl-C4-alkyl, and n is 2,3,4 or 5, preferably 2 or 3, especially 3, characterized in that an aniline derivative of the formula II
Ar NH2 in which Ar is as defined i8 reacted with a 2-alkoxycarbonylcycloAl~no~e of the formula III, 21~3 19~
-~I~,COOR1 (CH2)n in which Rl and n are as defined, in accordance with steps a) to c), and d) is subsequently treated with a base, preferably with an alkali metal hydroxide or an alkaline earth metal hydroxide, especially with S concentrated sodium hydroxide solution.
b) Process in which in step c) a pH of between 5.0 and 7.5 is established.
c) Process in which steps a) to c) are carried out in one apparatus without working up in the interim and at temperatures of between -20 and +25C.
d) Process in which in step d) the base is metered in slowly such that a pH of between 9.0 and 4.0, pre-ferably 8.0 and 5.0, is maintained.
e) Process in which the reaction is carried out with stirring and under an inert gas atmosphere.
The invention also relates to the use of the substituted phenylhydrazones prepared by one of Claims 1 to 6 for the preparation of indoles, characterized in that they are subjected in a manner known per se to the conditions of the Fischer indole synthesis.
The phenylhydrazones of the formula I are impor-tant intermediates in the preparation of substituted 3-indolylalkylamines, valuable pharmaceutical active substances having antihypertensive and antidepre~sant properties, especially of ~oY;n~ol~ (e.g. DE 28 27 874).
The process according to the invention is simple to carry out.
The molar ratio of aniline derivative to hydro-chloric acid can be chosen as desired. It is usual to 21 13 19~
work at a molar ratio of aniline derivative to hydro-chloric acid in the range from 1:1.8 to 1:4. This ratio is preferably from 1:2.0 to 1:2.8.
In general the hydrochloric acid i8 introduced as initial charge and the aniline derivative is added. The hydrochloric acid i~ preferably employed in the form of a 10 to 37 % aqueous solution.
An aqueous solution of sodium nitrite is added to the resulting aqueous solution of the anilinium hydro-chloride. The molar ratio of aniline derivative to sodiumnitrite is generally from 1:0.8 to 1:1.2, preferably from 1:0.9 to 1:1.1 and in particular from 1:1.0 to 1:1.05.
The solution of sodium nitrite is preferably em-ployed in the form of a 30 to 60 % solution.
~nder the conditions indicated the formation of the diazonium salt i~ generally complete after from 10 to 120 minutes.
The addition of the inert, water-immiscible solvent can be carried out before, during or after the addition of the 1,3-dicarbonyl compound. The 1,3-dicar-bonyl compound is preferably added, dissolved in the inert solvent, to the aqueous solution of the diazonium salt.
The molar ratio of aniline derivative to 1,3-dicarbonyl compound is preferably chosen such that from 0.8 to 1.2 mol, particularly preferably from 0.9 to 1.1 mol and in particular about 1.03 mol of 1,3-dicar-bonyl compound are employed per mole of aniline deriva-tive employed.
The weight ratio of 1,3-dicarbonyl compound of the inert solvent is generally chosen such that from 2 to 5 parts, preferably from 2.5 to 3.5 parts and in particular from 3 to 3.5 parts of solvent are employed per part of l,3-dicarbonyl compound.
The process according to the invention can be carried out, for example, at temperatures in the range from -25 to +25C. Preferred temperatures are in the range from -10 to +10C, particularly preferably in the range from -5 to +5C. The process according to the 2143~99 invention is usually carried out at atmospheric pressure.
However, it i8 also possible for it to be carried out at reduced or elevated pressure. The application of elevated pressure is particularly appropriate if it is desired to work at a reaction temperature at which the individual constituents of the reaction mixture boil at atmospheric pressure .
Solvents which are ~uitable are hydrocarbons, preferably aromatic hydrocarbons, such as benzene, toluene or xylene, especially toluene.
In the formulae I and II Ar is preferably a phenyl group which is substituted by from one to four, preferably one or two, C1-C10-alkyl or alkoxy groups.
In the compounds specified, at least one position ortho to the nitrogen atom is unsubstituted, but prefer-ably these compounds contain no substituent~ in the position ortho to the nitrogen atom.
In the preparation of the compounds of the formula I, a base is added to the mixture in step d).
Bases which are suitable for the process according to the invention are generally inorganic bases, for example alkali metal hydroxides and alkaline earth metal hydroxides. Particular preference i8 given to using sodium hydroxide or potassium hydroxide.
The ratio of the dicarbonyl compound employed to the base is preferably chosen such that from 0.9 to 1.7 equi~alents, particularly preferably from 1.1 to 1.5 equivalents, of base are employed per equivalent of 1,3-dicarbonyl compound.
The base is preferably added in the form of an 8 to 32 % aqueous solution. The addition is preferably made while monitoring the pH. At the end of the reaction a weakly acid pH of between 4.0 and 6.0, in particular between 5.0 and 5.5, is established.
The working-up of the reaction mixture is not critical. The product crystallizes out after 18 h, and preferably after from 30 to 48 h the crystals are iso-lated by filtration or centrifugation, washed with water and toluene and dried.
21~3~9~
The phenylhydrazones of the formula I are con-verted in a manner known per se, for example in accor-dance with W.J. Houlihan, ed., Chemistry of Heterocyclic Compounds - Indoles Pt 1, pp. 232-316 (1972) by reaction with Lewis acids, especially with zinc chloride, into the indoles of the formula III
(R)m ~ (CH2) ,-COOH
in which R1 and n are as defined R' is alkyl or alkoxy, and m is O, 1, 2, 3 or 4.
In accordance with the process according to the invention it is surprisingly possible, starting from aniline derivatives and 1,3-dicarbonyl compounds, to prepare phenylhydrazones in high yields and great purity in a one-part process. Consequently the process according to the invention is substantially more economical and achieves higher space-time yields in comparison with the process of the prior art.
Example 1 74.0 kg of p-anisidine are added, with stirring and cooling, to a mixture of 138.2 kg of concentrated hydrochloric acid and 395 1 of water, and the mixture is stirred at 0C under an inert gas atmosphere for two hours.
Sub~equently a solution of 42 kg of sodium nitrite in 60 1 of water is added over the course of 3 hours at temperatures of between O and +2C, and the mixture is stirred for a further 30 minutes.
Over the course of one hour a mixture of 102 kg of ethyl cycloh~y~ne-2-carboxylate and 347 kg of toluene is added at 0C and the mixture is stirred for a further 2 1 Ll 3 1 9 9 hour.
A mixture of 101 kg of 32 % sodium hydroxide solution and 248 1 of water is added to the resulting reaction mixture at temperatures of below 5C over the course of about 4 hours in such a way that a pH of 8 is not exceeded.
After crystallization, 136 kg of 6-carboethoxy-6-(4-methoxyphenylhydrazono)hexanecarboxylic acid are obtained from the reaction mixture (^ 70 % of theory based on p-anisidine, m.p.: 97C).
Comparative examPle p-Anisidine is reacted as described in Example 1, except that the ethyl cyclohexane-2-carboxylate is added to isopropanol instead of toluene.
A dark brown greasy mass is obtained which - even after addition of toluene - does not crystallize.
De~cription The invention relates to a process for the preparation of substituted phenylhydrazones from a diazonium salt and a 1,3-dicarbonyl compound. Substituted phenylhydrazones are valuable intermediates in the preparation of substituted indoles.
These compounds have previously been prepared in a two-stage process starting from the correspo~ing aniline derivatives:
The aniline derivative was first converted into an anilinium hydrochloride which, after isolation, was treated with an aqueous solution of sodium nitrite.
Subsequently the diazonium salt obtained in this way was reacted in a water-soluble medium with the 1,3-dicarbonyl compound.
However, if the anilinium hydrochloride is employed for the preparation of the phenylhydrazones without isolating it beforehand in the manner indicated, the product is obtained in the form of a dark brown greasy mass which does not crystallize even after addi-tion of nonpolar solvents and cannot be worked up or separated off.
The object of the present invention was to discover a process in which the anilinium hydrochloride need not be prepared and isolated in a prior reaction but is prepared directly in situ and processed further.
Surprisingly it has now been found that the prior isolation can be avoided, while nevertheless obtaining crystalline products, if the reaction with the 1,3-dicarbonyl compound is carried out not, as previously, ina one-phase protic solvent but in a two-phase system with a water-insoluble solvent.
The invention thus relates to a process for the preparation of substituted phenylhydrazones from a diazonium salt and a 1,3-dicarbonyl compound in which the following steps are carried out in succession:
a~ reaction of an aniline derivative with hydrochloric 21~13~99 acid, b) addition of an aqueous solution of sodium nitrite, c) reaction with the 1,3-dicarbonyl compound in an inert solvent, characterized in that in step c) a water-immiscible sol~ent is used, preferably an aromatic hydrocarbon, especially toluene.
a) Preferred embodiments are: process for the prepara-tion of phenylhydrazones of the formula I
Ar NH--N--I (CH2)n COOH
COOR' in which Ar is a phenyl group which is unsubstituted or is substituted by one or more alkyl or alkoxy groups, preferably a phenyl group which is mono-substituted by Cl10-alkoxy Rl is a Cl-C8-al~yl group, preferably Cl-C4-alkyl, and n is 2,3,4 or 5, preferably 2 or 3, especially 3, characterized in that an aniline derivative of the formula II
Ar NH2 in which Ar is as defined i8 reacted with a 2-alkoxycarbonylcycloAl~no~e of the formula III, 21~3 19~
-~I~,COOR1 (CH2)n in which Rl and n are as defined, in accordance with steps a) to c), and d) is subsequently treated with a base, preferably with an alkali metal hydroxide or an alkaline earth metal hydroxide, especially with S concentrated sodium hydroxide solution.
b) Process in which in step c) a pH of between 5.0 and 7.5 is established.
c) Process in which steps a) to c) are carried out in one apparatus without working up in the interim and at temperatures of between -20 and +25C.
d) Process in which in step d) the base is metered in slowly such that a pH of between 9.0 and 4.0, pre-ferably 8.0 and 5.0, is maintained.
e) Process in which the reaction is carried out with stirring and under an inert gas atmosphere.
The invention also relates to the use of the substituted phenylhydrazones prepared by one of Claims 1 to 6 for the preparation of indoles, characterized in that they are subjected in a manner known per se to the conditions of the Fischer indole synthesis.
The phenylhydrazones of the formula I are impor-tant intermediates in the preparation of substituted 3-indolylalkylamines, valuable pharmaceutical active substances having antihypertensive and antidepre~sant properties, especially of ~oY;n~ol~ (e.g. DE 28 27 874).
The process according to the invention is simple to carry out.
The molar ratio of aniline derivative to hydro-chloric acid can be chosen as desired. It is usual to 21 13 19~
work at a molar ratio of aniline derivative to hydro-chloric acid in the range from 1:1.8 to 1:4. This ratio is preferably from 1:2.0 to 1:2.8.
In general the hydrochloric acid i8 introduced as initial charge and the aniline derivative is added. The hydrochloric acid i~ preferably employed in the form of a 10 to 37 % aqueous solution.
An aqueous solution of sodium nitrite is added to the resulting aqueous solution of the anilinium hydro-chloride. The molar ratio of aniline derivative to sodiumnitrite is generally from 1:0.8 to 1:1.2, preferably from 1:0.9 to 1:1.1 and in particular from 1:1.0 to 1:1.05.
The solution of sodium nitrite is preferably em-ployed in the form of a 30 to 60 % solution.
~nder the conditions indicated the formation of the diazonium salt i~ generally complete after from 10 to 120 minutes.
The addition of the inert, water-immiscible solvent can be carried out before, during or after the addition of the 1,3-dicarbonyl compound. The 1,3-dicar-bonyl compound is preferably added, dissolved in the inert solvent, to the aqueous solution of the diazonium salt.
The molar ratio of aniline derivative to 1,3-dicarbonyl compound is preferably chosen such that from 0.8 to 1.2 mol, particularly preferably from 0.9 to 1.1 mol and in particular about 1.03 mol of 1,3-dicar-bonyl compound are employed per mole of aniline deriva-tive employed.
The weight ratio of 1,3-dicarbonyl compound of the inert solvent is generally chosen such that from 2 to 5 parts, preferably from 2.5 to 3.5 parts and in particular from 3 to 3.5 parts of solvent are employed per part of l,3-dicarbonyl compound.
The process according to the invention can be carried out, for example, at temperatures in the range from -25 to +25C. Preferred temperatures are in the range from -10 to +10C, particularly preferably in the range from -5 to +5C. The process according to the 2143~99 invention is usually carried out at atmospheric pressure.
However, it i8 also possible for it to be carried out at reduced or elevated pressure. The application of elevated pressure is particularly appropriate if it is desired to work at a reaction temperature at which the individual constituents of the reaction mixture boil at atmospheric pressure .
Solvents which are ~uitable are hydrocarbons, preferably aromatic hydrocarbons, such as benzene, toluene or xylene, especially toluene.
In the formulae I and II Ar is preferably a phenyl group which is substituted by from one to four, preferably one or two, C1-C10-alkyl or alkoxy groups.
In the compounds specified, at least one position ortho to the nitrogen atom is unsubstituted, but prefer-ably these compounds contain no substituent~ in the position ortho to the nitrogen atom.
In the preparation of the compounds of the formula I, a base is added to the mixture in step d).
Bases which are suitable for the process according to the invention are generally inorganic bases, for example alkali metal hydroxides and alkaline earth metal hydroxides. Particular preference i8 given to using sodium hydroxide or potassium hydroxide.
The ratio of the dicarbonyl compound employed to the base is preferably chosen such that from 0.9 to 1.7 equi~alents, particularly preferably from 1.1 to 1.5 equivalents, of base are employed per equivalent of 1,3-dicarbonyl compound.
The base is preferably added in the form of an 8 to 32 % aqueous solution. The addition is preferably made while monitoring the pH. At the end of the reaction a weakly acid pH of between 4.0 and 6.0, in particular between 5.0 and 5.5, is established.
The working-up of the reaction mixture is not critical. The product crystallizes out after 18 h, and preferably after from 30 to 48 h the crystals are iso-lated by filtration or centrifugation, washed with water and toluene and dried.
21~3~9~
The phenylhydrazones of the formula I are con-verted in a manner known per se, for example in accor-dance with W.J. Houlihan, ed., Chemistry of Heterocyclic Compounds - Indoles Pt 1, pp. 232-316 (1972) by reaction with Lewis acids, especially with zinc chloride, into the indoles of the formula III
(R)m ~ (CH2) ,-COOH
in which R1 and n are as defined R' is alkyl or alkoxy, and m is O, 1, 2, 3 or 4.
In accordance with the process according to the invention it is surprisingly possible, starting from aniline derivatives and 1,3-dicarbonyl compounds, to prepare phenylhydrazones in high yields and great purity in a one-part process. Consequently the process according to the invention is substantially more economical and achieves higher space-time yields in comparison with the process of the prior art.
Example 1 74.0 kg of p-anisidine are added, with stirring and cooling, to a mixture of 138.2 kg of concentrated hydrochloric acid and 395 1 of water, and the mixture is stirred at 0C under an inert gas atmosphere for two hours.
Sub~equently a solution of 42 kg of sodium nitrite in 60 1 of water is added over the course of 3 hours at temperatures of between O and +2C, and the mixture is stirred for a further 30 minutes.
Over the course of one hour a mixture of 102 kg of ethyl cycloh~y~ne-2-carboxylate and 347 kg of toluene is added at 0C and the mixture is stirred for a further 2 1 Ll 3 1 9 9 hour.
A mixture of 101 kg of 32 % sodium hydroxide solution and 248 1 of water is added to the resulting reaction mixture at temperatures of below 5C over the course of about 4 hours in such a way that a pH of 8 is not exceeded.
After crystallization, 136 kg of 6-carboethoxy-6-(4-methoxyphenylhydrazono)hexanecarboxylic acid are obtained from the reaction mixture (^ 70 % of theory based on p-anisidine, m.p.: 97C).
Comparative examPle p-Anisidine is reacted as described in Example 1, except that the ethyl cyclohexane-2-carboxylate is added to isopropanol instead of toluene.
A dark brown greasy mass is obtained which - even after addition of toluene - does not crystallize.
Claims (7)
1. Process for the preparation of substituted phenylhydrazones from a diazonium salt and a 1,3-dicar-bonyl compound in which the following steps are carried out in succession:
a) reaction of an aniline derivative with hydrochloric acid, b) addition of an aqueous solution of sodium nitrite, c) reaction with the 1,3-dicarbonyl compound in an inert solvent, characterized in that in step c) a water-immiscible solvent is used, preferably an aromatic hydrocarbon.
a) reaction of an aniline derivative with hydrochloric acid, b) addition of an aqueous solution of sodium nitrite, c) reaction with the 1,3-dicarbonyl compound in an inert solvent, characterized in that in step c) a water-immiscible solvent is used, preferably an aromatic hydrocarbon.
2. Process for the preparation of phenyl hydrazones of the formula I
I
in which Ar is a phenyl group which is unsubstituted or is substituted by one or more alkyl or alkoxy groups, R1 is a C1-C8-alkyl group, and n is 2,3,4 or 5, characterized in that an aniline derivative of the formula II
in which Ar is as defined is reacted with a 2-alkoxycarbonylcycloalkanone of the formula III, III
in which R1 and n are as defined, in accordance with Claim 1, and d) is then treated with a base, preferably with an alkali metal hydroxide or alkaline earth metal hydroxide.
I
in which Ar is a phenyl group which is unsubstituted or is substituted by one or more alkyl or alkoxy groups, R1 is a C1-C8-alkyl group, and n is 2,3,4 or 5, characterized in that an aniline derivative of the formula II
in which Ar is as defined is reacted with a 2-alkoxycarbonylcycloalkanone of the formula III, III
in which R1 and n are as defined, in accordance with Claim 1, and d) is then treated with a base, preferably with an alkali metal hydroxide or alkaline earth metal hydroxide.
3. Process according to one of Claims 1 and 2, characterized in that in step c) a pH of between 5.0 and 7.5 is established.
4. Process according to one of the preceding claims, characterized in that steps a) to c) are carried out in one apparatus without working up in the interim and at temperatures of between -20° and +25°C.
5. Process according to one of Claims 2, 3 and 4, characterized in that in step d) the base is metered in slowly such that a pH of between 9.0 and 4.0, preferably 8.0 and 5.0, is maintained.
6. Process according to one of the preceding claims, characterized in that the reaction is carried out with stirring and under an inert gas atmosphere.
7. Use of the substituted phenylhydrazones prepared according to one of the preceding claims for the prepara-tion of indoles, characterized in that they are subjected in a manner known per se to the conditions of the Fischer indole synthesis.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4406663.5 | 1994-03-01 | ||
| DE4406663A DE4406663A1 (en) | 1994-03-01 | 1994-03-01 | Process for the preparation of substituted phenylhydrazone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2143499A1 true CA2143499A1 (en) | 1995-09-02 |
Family
ID=6511519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002143499A Abandoned CA2143499A1 (en) | 1994-03-01 | 1995-02-27 | Process for the preparation of substituted phenylhydrazones |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0670304A1 (en) |
| JP (1) | JPH07267913A (en) |
| KR (1) | KR950032092A (en) |
| CN (1) | CN1111617A (en) |
| AU (1) | AU1349295A (en) |
| CA (1) | CA2143499A1 (en) |
| DE (1) | DE4406663A1 (en) |
| HU (1) | HUT72808A (en) |
| ZA (1) | ZA951659B (en) |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2045881A1 (en) * | 1970-09-17 | 1972-03-23 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Alpha-chloro-alpha-formylcarbonyl phenylhydrazones - prepn - from diazotised anilines and chloroacetaldehyde, used as inse |
| GB8821448D0 (en) * | 1988-09-13 | 1988-10-12 | Ici Plc | Pyridazinone manufacture |
| US5258523A (en) * | 1991-06-28 | 1993-11-02 | Lonza Ltd. | Process for the production of 2-aryl-2H-1,2,3-triazoles |
-
1994
- 1994-03-01 DE DE4406663A patent/DE4406663A1/en not_active Ceased
-
1995
- 1995-02-16 EP EP95102121A patent/EP0670304A1/en not_active Withdrawn
- 1995-02-24 AU AU13492/95A patent/AU1349295A/en not_active Abandoned
- 1995-02-27 CA CA002143499A patent/CA2143499A1/en not_active Abandoned
- 1995-02-27 JP JP7037966A patent/JPH07267913A/en active Pending
- 1995-02-27 CN CN95100820A patent/CN1111617A/en active Pending
- 1995-02-28 ZA ZA951659A patent/ZA951659B/en unknown
- 1995-02-28 KR KR1019950003986A patent/KR950032092A/en not_active Application Discontinuation
- 1995-02-28 HU HU9500616A patent/HUT72808A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUT72808A (en) | 1996-05-28 |
| ZA951659B (en) | 1995-12-08 |
| JPH07267913A (en) | 1995-10-17 |
| KR950032092A (en) | 1995-12-20 |
| DE4406663A1 (en) | 1995-09-07 |
| HU9500616D0 (en) | 1995-04-28 |
| EP0670304A1 (en) | 1995-09-06 |
| AU1349295A (en) | 1995-09-07 |
| CN1111617A (en) | 1995-11-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6703505B2 (en) | Process for the preparation of high purity Pemirolast | |
| IL31082A (en) | Derivatives of heptenoic acid | |
| CA2143499A1 (en) | Process for the preparation of substituted phenylhydrazones | |
| US4515950A (en) | Process for the isomerization of ergovine derivatives | |
| JPH0670049B2 (en) | Method for N-alkylation of dihydrolysergic acid | |
| US4892958A (en) | Preparation of 5-amino-1-phenyl-4-nitropyrazoles | |
| US6515141B1 (en) | Process for the preparation of indole derivatives or salts thereof | |
| CA2227131C (en) | Methods for the preparation of benzophenone derivatives | |
| EP0347136B1 (en) | Method for reducing aromatic nitro groups | |
| HU187471B (en) | Process for preparing n-acyl-triptamine derivatives and pharmaceutical compositions containing them as active agents | |
| KR100745449B1 (en) | Method for production of benzofuranone oximes | |
| EP0790233B1 (en) | Method of producing 2-hydrazinonaphtalene compound | |
| EP0047674A1 (en) | Novel process for preparing isoindolin derivatives | |
| US20060247427A1 (en) | Process to obtain 6-O-methylerythromycin a (clarithromycin)_form II | |
| US4772747A (en) | Preparation of 2,4,6-trichlorophenylhydrazine | |
| US5179211A (en) | Process for the preparation of indoles | |
| CA2291508A1 (en) | An improved process for preparing 4-amino-1,2,4-triazolin-5-ones | |
| JPH0672142B2 (en) | Method for producing 4-amino-1,2,4-triazoline-5-thione compound | |
| US7049459B2 (en) | 1-[(4-methyl thio)phenyl]-2-(phenyl acetoxy)-1-ethanone and a process for preparing the same | |
| US6008413A (en) | Process for recrystallizing 1,3-bis(aminophenoxy benzene) | |
| JP3151687B2 (en) | Method for synthesizing 4-amino-o-quinone derivative and 3-amino-6-arylazophenol derivative | |
| EP0437567B1 (en) | Phenyl-glycine derivatives | |
| CA2057156A1 (en) | Selective acylation of hydrazines | |
| US20230416189A1 (en) | New synthesis of l-phenylalanine butyramide | |
| US20040186300A1 (en) | Process for the preparation of zafirlukast |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |