CA1279066C - Process for the preparation of halothiophene-2-carboxylic acids - Google Patents
Process for the preparation of halothiophene-2-carboxylic acidsInfo
- Publication number
- CA1279066C CA1279066C CA000518931A CA518931A CA1279066C CA 1279066 C CA1279066 C CA 1279066C CA 000518931 A CA000518931 A CA 000518931A CA 518931 A CA518931 A CA 518931A CA 1279066 C CA1279066 C CA 1279066C
- Authority
- CA
- Canada
- Prior art keywords
- oxygen
- halothiophene
- carboxylic acids
- oxidation
- halo
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Catalysts (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula where n = 1 or 2 Hal = halogen by oxidation of the appropriate halo-2-acylthiophenes of the general formula where x = 0 to 3.
The oxidation is carried out in a solvent using oxygen in the presence of a catalyst.
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula where n = 1 or 2 Hal = halogen by oxidation of the appropriate halo-2-acylthiophenes of the general formula where x = 0 to 3.
The oxidation is carried out in a solvent using oxygen in the presence of a catalyst.
Description
~;~'7~
HOECHS~ AKTlENGESELLSCHAFT HOE 85~F 206 Dr.MA/mU
A PROCESS FOR THE PREPARATION ~F HALOTHIOPHENE-2-CARBOXYLIC ACIDS
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula (Hal)n ~ ~here n = 1 or 2 S ~OOH Hal = halogen Halothiophene-2-carboxyl;c acids are known as valuab~e intermediates for the preparation of pharmaceutical prepar-ations. For example, a series of heterocyclic compounds which can be used, inter alia, as analgesic agents, is synthesized from 3-chlorothiophene-2-carboxylic acid (US
Patent 4,230,873 = German Offenlegungsschrift 2,706,873).
S-Chlorothiophene-2-carboxyLic acid serves as a synthesis component for the preparation of compounds having a chol-esterol- and lipid-reducing action (US Patent 4,017,514).
Heterocyclic compounds having a s~eetener character have also already been prepared from halothiophene-2-carboxy~ic acids tUS Patent 4,028,373).
`':, ; ~ 20 It is kno~n that halothiophene-2-carboxylic acids can be prepared by oxidation of the appropriate halo-2-acetylthio-phene - also known as 1-(halo-t2)-thienyl)-ethanone - using aqueous permanganate solution or using alkaline, aqueous sodium hyperchlorite solution tJ. Am. Chem. Soc., 69, 3098, (1947)). In this case, ho~ever, considerable problems are caused by the production of inorganic salts in the liquid ~aste, since the hypochlorite solution must be used in 3-fold excess and destroyed after the oxidation using bisulfite solution ~Org. Synth., Coll. Vol. II, 428 (1943)).
~" 30 The reaction mixture is finally acidified to precipitate :
the free thiophene-2-carboxylic acids.
The object ~3S to convert halo-2-acylthiophenes, ~hich are generally easily accessible by acylation of halothiophenes : , .. . . . .
.
. , .
,:
-'~' ' ' ~75~
HOECHS~ AKTlENGESELLSCHAFT HOE 85~F 206 Dr.MA/mU
A PROCESS FOR THE PREPARATION ~F HALOTHIOPHENE-2-CARBOXYLIC ACIDS
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula (Hal)n ~ ~here n = 1 or 2 S ~OOH Hal = halogen Halothiophene-2-carboxyl;c acids are known as valuab~e intermediates for the preparation of pharmaceutical prepar-ations. For example, a series of heterocyclic compounds which can be used, inter alia, as analgesic agents, is synthesized from 3-chlorothiophene-2-carboxylic acid (US
Patent 4,230,873 = German Offenlegungsschrift 2,706,873).
S-Chlorothiophene-2-carboxyLic acid serves as a synthesis component for the preparation of compounds having a chol-esterol- and lipid-reducing action (US Patent 4,017,514).
Heterocyclic compounds having a s~eetener character have also already been prepared from halothiophene-2-carboxy~ic acids tUS Patent 4,028,373).
`':, ; ~ 20 It is kno~n that halothiophene-2-carboxylic acids can be prepared by oxidation of the appropriate halo-2-acetylthio-phene - also known as 1-(halo-t2)-thienyl)-ethanone - using aqueous permanganate solution or using alkaline, aqueous sodium hyperchlorite solution tJ. Am. Chem. Soc., 69, 3098, (1947)). In this case, ho~ever, considerable problems are caused by the production of inorganic salts in the liquid ~aste, since the hypochlorite solution must be used in 3-fold excess and destroyed after the oxidation using bisulfite solution ~Org. Synth., Coll. Vol. II, 428 (1943)).
~" 30 The reaction mixture is finally acidified to precipitate :
the free thiophene-2-carboxylic acids.
The object ~3S to convert halo-2-acylthiophenes, ~hich are generally easily accessible by acylation of halothiophenes : , .. . . . .
.
. , .
,:
-'~' ' ' ~75~
(J. Am. Chem. Soc~, 69, 3093-3097, (1947)), to the halothiophene-2-carboxylic acids by means of a technically simple oxidation method, avolding the problems mentioned.
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula tHal )n ~3~
S COOH
in which Hal denotes halogen and n denotes 1 or 2, by oxidation of the appropriate halo-2-acylthiophenes of the general formula ( Hal ) n~
.~., S C-(CH2)~C-C~3 .
where x - O to 3, wherein the oxidation is carried out in a solvent stable towards oxygen in the used temperature range using oxygen in the presence of salts of manganese, cobalt, chromium or ~ 20 iron as a catalyst.
., ; The novel process allows the preparation of halothiophene-2-carboxylic acids in high yields using a widely available oxidant.
~Furthermore, it has the advantage that virtually no environmentally polluting waste salts or liquid wastes are produced and the isolation of the halothiophene-2-carboxylic acids is achieved in a particularly simple fashion.
'''.`~
'''' ~ .
' ~ ' - . . ~ ,:
- - : , - . . , - - ~, -, . , - -- :- , . -..
- - ,- .
2a 23221-4282 It is surprising here that formation of sulfones only occurs to a limited extent under the reaction conditions used in the process according to the invention.
All mono-and dihalo-2-acylthiophenes are suitable as starting materials for the oxidation according to the invention.
The followlng can be used as halogen derivatives: fluorine, :
- "'i.
' :, , s :., .., '1 ~:
.
- - .
~:' " . ` ' '" :.
,~'' ~ - - .
,'- ~ '~ ' ` ~ .
~' '., ~ ' , chlorine, bromine and iodine der;vatives. ~ecause of the thermal lability of the iodine derivatives and the poor accessibility of the fluorine derivatives, the der;vatives of chlorine and bromine are particularly i~portant, above all the chlorine derivatives.
The acyl radical in the halo-2-acylthiophenes used as starting material can be acetyl, propionyl, butyryl or pivaly~. ~ecause of the wide availability of acetic an-hydride, the acyl radical is preferably acetyl.
All solYents which are stable toward oxygen ;n the tempera-ture range used are suitable as solvent ~hen carrying out the oxidation. Ho~ever, al;phatic carboxylic acids having up to five carbon atoms, such as, for example, acetic acid, propionic ac;d or pival;c acid, are preferred. Acetic acid is particularly preferred.
The weight ratio of solvent to halo-2-acy~thiophene is not of overriding importance and is, in general, about 4:1 to 20:1. The range 6:1 to 12:1 is particularly favorable.
In general, salts of manganese, cobalt, chromium or iron can be used as catalysts, above all the halides, carboxy-lates, carbonates or sulfates of these metals.
Manganese and cobalt are preferred, particularLy mixtures thereof, a ~eight ratio of manganese:cobalt of 10:1 to 20:1 having proven favorable.
, The metal salts are dissolved in the solvent. In the case of the preferred use of aliphatic carboxylic acids as solvents, it has proven favorable to use the carboxylates of the metals, preferably those metal carboxylates ~hich are derived from the carboxylic acid used as solvent. The ~ 30 acetates are therefore particularly preferred metal salts.
-~ The weight ratio of catalyst (calculated as the metal) to halo-2-acylthiophene is, in general, 0.4:100 to 20:100, .. . . ,, ~ -: - , .
- ~ ' ' - ' ~
- ~ ~
1~'7~ 0 preferably 1:100 to 10:100.
Oxygen serves as oxidant, either in pure form or in mix-tures with inert gases, such as, for example, nitrogen or carbon dioxide. Air ~hich has been enriched ~ith oxygen, particularly containing about 50% by volume of oxygen, is preferably used.
The reaction temperature is, in general, 50 to 200C.
The ideal reaction temperature depends, inter alia, on the thermal stability of the acyl derivatives employed and of the carboxylic acid derivat;ves produced, and can be deter-mined by a simple preliminary experiment. For example, uhen monohalo-2-acetylthiophenes are employed, a tempera-ture range of 80 to 140C proves advantageous.
The oxidation is, in general, carried out in the pressure range of 1 to 20 bar. Ho~ever, it is an advantage of the process according to the invention that, in general, high conversions of at least 90~ and good yields of about 90%
can be achieved in reaction times of up to about 6 hours, even in the case of a non-pressurized procedure.
~20 The oxidation can be carried out both in batches and also - continuously in conventional reactors such as kettles, kettle cascades or bubble column reactors.
~:
The reaction product is vorked up in a simple fashion, by distilling off the solvent, ~hich, after further distill-ative purification, can be reused. The crude reaction product obtained in this fashion as a distillation residue is washed ~ith water to remove adherent salts. The halo-thiophene-2-carboxylic acids uhich are produced trom this as solid products can easily be purified by recrystalliza-tion.
. ~
The reaction is carried out in an unjacketed reaction tube, ~ith a base frit, of 3.1 liter capacity, a length of 110 cm ..
~ ,- . '' - ~ ' - ~
. . .
. , , : , :,~ ' ,~ . '' ' 7~ 6 and an internal diameter ot 60 mm. The reaction tube is filled ~ith a solution of 240 9 ~1.5 mol) of 1-~5-chloro-~2)-thienyl)-ethanone ~m.p. 48C), 1.5 9 of cobalt acetate . 4 H20 and 24.0 9 of manganese acetate . 4 H20 in 1.8 liters of glacial acetic acid, and the solution is heated to 105-106C
by means of oil-circulation heating while a gas stream of 25 liters of oxygen per hour is passed through the solution.
The internal temperature then increases within an hour to 108-110C and is kept constant in this range for the further duration of the experiment. Approximately 4 hours after the start of the experiment, the reaction solution ~2116 9) is let out while still hot and concentrated to dryness in a rot-ary evaporator. The dry crude product of carboxylic acid, 220 9 ~90.2X yield), is recrystallized from 10% strength aqueous methanol; 196 9 of crystalline 5-chlorothiophene-2-carboxylic acid of melt-ing point 152C remain.
. .
The reaction is carried out in the same apparatus as in Example 1.
A solution of 120 9 ~0.75 ol) of 1-t3-chloro-(2)-thienyl)-ethanone (b.p. 85C/2 bar), 0.5 9 of cobalt acetate .
; 4 H20 and 18.0 9 of anganese acetate . 4 H20 in 1.2 liters of glacial acetic acid is introduced into the reaction tube -~ and heated to a tenperature of 105-106C. A gas stream of 25 liters of oxygen per hour is simultaneously passed through the solution, so that the internal temperature rises to 108-110C within one hour and is kept constant at this temper-ature for the further duration of the experinent. Approxi-oately 3.5 hours after the start of the experi-ent, the reaction solution (1322 9) is let out while still hot and ~orked up as in Example 1. ~he 88 9 of crude product which ; ~ remain are recrystalli2ed fro- 3X strength acetic acid. 68 9 ~- ~ of 3-chlorothiophene-2-carboxylic acid, corresponding to a ield of 55.8X, relative to the starting material employed, renain as crystals. Howe~er, since the ketone mixture ; e-ployed only contains bout an 80X by weight of : ::
'~ ;: : ~ . ' ,',''". . : `, .
--- . : - :- . : .
: : :. ' : :
1-(3-chloro-~2)-thienyl)-ethanone, a selectivity of 70X is calculated for the 3-chlorothiophene-2-carboxylic acid ob-tained~ After recrystallization from water, the product melts at 188-190C.
The procedure as in Example 1 is carried out, but with the difference that, in place of pure oxygen, a gas mixture of 15 liters of oxygen and 15 liters of nitrogen per hour is passed through the solution. After an experimental duration of about 4.5 hours, the hot reaction solution is let out and - worked up as in Example 1. 228 9 of dry crude product and after recrystalli2ation from 15% strength methanol, 205 9 of crystalline 5-chlorothiophene-2-carboxylic acid, corres-ponding to a pure yield of 84.0%, are finally obtained.
'", ,;, .:
., ; .
'~
`''~' :, ....
: .~ ,. .
. ~, , .
.. . .. .
-, . -- . - .
'. ', ' : , . , .'. .,, ~ '' .
The invention relates to a process for the preparation of halothiophene-2-carboxylic acids of the general formula tHal )n ~3~
S COOH
in which Hal denotes halogen and n denotes 1 or 2, by oxidation of the appropriate halo-2-acylthiophenes of the general formula ( Hal ) n~
.~., S C-(CH2)~C-C~3 .
where x - O to 3, wherein the oxidation is carried out in a solvent stable towards oxygen in the used temperature range using oxygen in the presence of salts of manganese, cobalt, chromium or ~ 20 iron as a catalyst.
., ; The novel process allows the preparation of halothiophene-2-carboxylic acids in high yields using a widely available oxidant.
~Furthermore, it has the advantage that virtually no environmentally polluting waste salts or liquid wastes are produced and the isolation of the halothiophene-2-carboxylic acids is achieved in a particularly simple fashion.
'''.`~
'''' ~ .
' ~ ' - . . ~ ,:
- - : , - . . , - - ~, -, . , - -- :- , . -..
- - ,- .
2a 23221-4282 It is surprising here that formation of sulfones only occurs to a limited extent under the reaction conditions used in the process according to the invention.
All mono-and dihalo-2-acylthiophenes are suitable as starting materials for the oxidation according to the invention.
The followlng can be used as halogen derivatives: fluorine, :
- "'i.
' :, , s :., .., '1 ~:
.
- - .
~:' " . ` ' '" :.
,~'' ~ - - .
,'- ~ '~ ' ` ~ .
~' '., ~ ' , chlorine, bromine and iodine der;vatives. ~ecause of the thermal lability of the iodine derivatives and the poor accessibility of the fluorine derivatives, the der;vatives of chlorine and bromine are particularly i~portant, above all the chlorine derivatives.
The acyl radical in the halo-2-acylthiophenes used as starting material can be acetyl, propionyl, butyryl or pivaly~. ~ecause of the wide availability of acetic an-hydride, the acyl radical is preferably acetyl.
All solYents which are stable toward oxygen ;n the tempera-ture range used are suitable as solvent ~hen carrying out the oxidation. Ho~ever, al;phatic carboxylic acids having up to five carbon atoms, such as, for example, acetic acid, propionic ac;d or pival;c acid, are preferred. Acetic acid is particularly preferred.
The weight ratio of solvent to halo-2-acy~thiophene is not of overriding importance and is, in general, about 4:1 to 20:1. The range 6:1 to 12:1 is particularly favorable.
In general, salts of manganese, cobalt, chromium or iron can be used as catalysts, above all the halides, carboxy-lates, carbonates or sulfates of these metals.
Manganese and cobalt are preferred, particularLy mixtures thereof, a ~eight ratio of manganese:cobalt of 10:1 to 20:1 having proven favorable.
, The metal salts are dissolved in the solvent. In the case of the preferred use of aliphatic carboxylic acids as solvents, it has proven favorable to use the carboxylates of the metals, preferably those metal carboxylates ~hich are derived from the carboxylic acid used as solvent. The ~ 30 acetates are therefore particularly preferred metal salts.
-~ The weight ratio of catalyst (calculated as the metal) to halo-2-acylthiophene is, in general, 0.4:100 to 20:100, .. . . ,, ~ -: - , .
- ~ ' ' - ' ~
- ~ ~
1~'7~ 0 preferably 1:100 to 10:100.
Oxygen serves as oxidant, either in pure form or in mix-tures with inert gases, such as, for example, nitrogen or carbon dioxide. Air ~hich has been enriched ~ith oxygen, particularly containing about 50% by volume of oxygen, is preferably used.
The reaction temperature is, in general, 50 to 200C.
The ideal reaction temperature depends, inter alia, on the thermal stability of the acyl derivatives employed and of the carboxylic acid derivat;ves produced, and can be deter-mined by a simple preliminary experiment. For example, uhen monohalo-2-acetylthiophenes are employed, a tempera-ture range of 80 to 140C proves advantageous.
The oxidation is, in general, carried out in the pressure range of 1 to 20 bar. Ho~ever, it is an advantage of the process according to the invention that, in general, high conversions of at least 90~ and good yields of about 90%
can be achieved in reaction times of up to about 6 hours, even in the case of a non-pressurized procedure.
~20 The oxidation can be carried out both in batches and also - continuously in conventional reactors such as kettles, kettle cascades or bubble column reactors.
~:
The reaction product is vorked up in a simple fashion, by distilling off the solvent, ~hich, after further distill-ative purification, can be reused. The crude reaction product obtained in this fashion as a distillation residue is washed ~ith water to remove adherent salts. The halo-thiophene-2-carboxylic acids uhich are produced trom this as solid products can easily be purified by recrystalliza-tion.
. ~
The reaction is carried out in an unjacketed reaction tube, ~ith a base frit, of 3.1 liter capacity, a length of 110 cm ..
~ ,- . '' - ~ ' - ~
. . .
. , , : , :,~ ' ,~ . '' ' 7~ 6 and an internal diameter ot 60 mm. The reaction tube is filled ~ith a solution of 240 9 ~1.5 mol) of 1-~5-chloro-~2)-thienyl)-ethanone ~m.p. 48C), 1.5 9 of cobalt acetate . 4 H20 and 24.0 9 of manganese acetate . 4 H20 in 1.8 liters of glacial acetic acid, and the solution is heated to 105-106C
by means of oil-circulation heating while a gas stream of 25 liters of oxygen per hour is passed through the solution.
The internal temperature then increases within an hour to 108-110C and is kept constant in this range for the further duration of the experiment. Approximately 4 hours after the start of the experiment, the reaction solution ~2116 9) is let out while still hot and concentrated to dryness in a rot-ary evaporator. The dry crude product of carboxylic acid, 220 9 ~90.2X yield), is recrystallized from 10% strength aqueous methanol; 196 9 of crystalline 5-chlorothiophene-2-carboxylic acid of melt-ing point 152C remain.
. .
The reaction is carried out in the same apparatus as in Example 1.
A solution of 120 9 ~0.75 ol) of 1-t3-chloro-(2)-thienyl)-ethanone (b.p. 85C/2 bar), 0.5 9 of cobalt acetate .
; 4 H20 and 18.0 9 of anganese acetate . 4 H20 in 1.2 liters of glacial acetic acid is introduced into the reaction tube -~ and heated to a tenperature of 105-106C. A gas stream of 25 liters of oxygen per hour is simultaneously passed through the solution, so that the internal temperature rises to 108-110C within one hour and is kept constant at this temper-ature for the further duration of the experinent. Approxi-oately 3.5 hours after the start of the experi-ent, the reaction solution (1322 9) is let out while still hot and ~orked up as in Example 1. ~he 88 9 of crude product which ; ~ remain are recrystalli2ed fro- 3X strength acetic acid. 68 9 ~- ~ of 3-chlorothiophene-2-carboxylic acid, corresponding to a ield of 55.8X, relative to the starting material employed, renain as crystals. Howe~er, since the ketone mixture ; e-ployed only contains bout an 80X by weight of : ::
'~ ;: : ~ . ' ,',''". . : `, .
--- . : - :- . : .
: : :. ' : :
1-(3-chloro-~2)-thienyl)-ethanone, a selectivity of 70X is calculated for the 3-chlorothiophene-2-carboxylic acid ob-tained~ After recrystallization from water, the product melts at 188-190C.
The procedure as in Example 1 is carried out, but with the difference that, in place of pure oxygen, a gas mixture of 15 liters of oxygen and 15 liters of nitrogen per hour is passed through the solution. After an experimental duration of about 4.5 hours, the hot reaction solution is let out and - worked up as in Example 1. 228 9 of dry crude product and after recrystalli2ation from 15% strength methanol, 205 9 of crystalline 5-chlorothiophene-2-carboxylic acid, corres-ponding to a pure yield of 84.0%, are finally obtained.
'", ,;, .:
., ; .
'~
`''~' :, ....
: .~ ,. .
. ~, , .
.. . .. .
-, . -- . - .
'. ', ' : , . , .'. .,, ~ '' .
Claims (9)
1. A process for the preparation of halothiophene-2-carboxylic acids of the general formula in which Hal denotes halogen and n denotes 1 or 2, by oxidation of the appropriate halo-2-acylthiophenes of the general formula where x = 0 to 3, wherein the oxidation is carried out in a solvent stable toward oxygen in the used temperature range using oxygen in the presence of salts of manganese, cobalt, chromium or iron as a catalyst.
2. The process as claimed in claim 1, wherein the reaction temperature used is 50 to 200°C.
3. The process as claimed in claim 1, wherein Mn, Co, Cr or Fe in the form of salts are employed as catalysts, either alone or in mixtures with one another.
4. The process as claimed in claim 1, 2 or 3, wherein the weight ratio of catalyst (calculated as the metal) to halo-2-acylthiophene is 0.4:20 to 20:100.
5. The process as claimed in claim 1, 2 or 3, wherein an aliphatic carboxylic acid is used as solvent.
6. The process as claimed in claim 1, 2 or 3, wherein oxygen-enriched air is employed as oxidant.
7. The process as claimed in claim 1, 2 or 3, wherein the halo-2-acetylthiophenes (x = 0) are employed as starting compounds.
8. The process as claimed in claim 1, 2 or 3, wherein a mixture of manganese and cobalt salt is used as catalyst.
9. The process as claimed in claim 8, wherein the weight ratio of manganese:cobalt is 10:1 to 20:1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853534286 DE3534286A1 (en) | 1985-09-26 | 1985-09-26 | METHOD FOR PRODUCING HALOGENTHIOPHENE-2-CARBONIC ACIDS |
| DEP3534286.2 | 1985-09-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1279066C true CA1279066C (en) | 1991-01-15 |
Family
ID=6281971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000518931A Expired - Fee Related CA1279066C (en) | 1985-09-26 | 1986-09-25 | Process for the preparation of halothiophene-2-carboxylic acids |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0216279B1 (en) |
| JP (1) | JPS6272685A (en) |
| CA (1) | CA1279066C (en) |
| DE (2) | DE3534286A1 (en) |
| HU (1) | HU196984B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109195961A (en) * | 2016-03-24 | 2019-01-11 | 孟山都技术公司 | The method for being used to prepare heteroaryl carboxylic acid |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3743517A1 (en) * | 1987-12-22 | 1989-07-06 | Basf Ag | METHOD FOR PRODUCING AROMATIC HYDROXYCARBONIC ACIDS |
| DE3743518A1 (en) * | 1987-12-22 | 1989-07-06 | Basf Ag | METHOD FOR PRODUCING AROMATIC DICARBONIC ACIDS |
| WO1994012505A1 (en) * | 1992-11-23 | 1994-06-09 | Pfizer Inc. | Regioselective synthesis of 4-chloro-2-thiophenecarboxylic acid |
| CN102993164A (en) * | 2012-11-19 | 2013-03-27 | 连云港宏业化工有限公司 | Preparation method for 2-chlorine-5-thiophene formic acid |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2462697A (en) * | 1947-03-25 | 1949-02-22 | Du Pont | Thiophene-2-carboxylic acid |
| US2492645A (en) * | 1949-02-04 | 1949-12-27 | Socony Vacuum Oil Co Inc | Production of thiophenecarboxylic acid |
| CA1066711A (en) * | 1974-08-26 | 1979-11-20 | Hoffmann-La Roche Limited | Thiophene derivatives |
-
1985
- 1985-09-26 DE DE19853534286 patent/DE3534286A1/en not_active Withdrawn
-
1986
- 1986-09-13 EP EP86112679A patent/EP0216279B1/en not_active Expired
- 1986-09-13 DE DE8686112679T patent/DE3663520D1/en not_active Expired
- 1986-09-24 HU HU864062A patent/HU196984B/en not_active IP Right Cessation
- 1986-09-25 CA CA000518931A patent/CA1279066C/en not_active Expired - Fee Related
- 1986-09-25 JP JP61225073A patent/JPS6272685A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109195961A (en) * | 2016-03-24 | 2019-01-11 | 孟山都技术公司 | The method for being used to prepare heteroaryl carboxylic acid |
Also Published As
| Publication number | Publication date |
|---|---|
| HUT44777A (en) | 1988-04-28 |
| EP0216279A1 (en) | 1987-04-01 |
| JPS6272685A (en) | 1987-04-03 |
| DE3534286A1 (en) | 1987-04-02 |
| EP0216279B1 (en) | 1989-05-24 |
| HU196984B (en) | 1989-02-28 |
| DE3663520D1 (en) | 1989-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Koh et al. | Stereoselective SN2 Reactions of the (R)-Pantolactone Ester of Racemic. alpha.-Halo Carboxylic Acids with Aryl Oxides. A Synthesis of (S)-2-Aryloxy and (S)-2-Hydroxy Acids | |
| CA1279066C (en) | Process for the preparation of halothiophene-2-carboxylic acids | |
| US5663418A (en) | Processes for the preparation of cyclopropanecarboxylic acid and derivatives thereof | |
| JPH08500360A (en) | Method for producing phenyl terephthalic acid | |
| CA2063979C (en) | Process for the preparation of alkanesulfonylbenzoic acids | |
| US5498799A (en) | Process for producing optically active 2-norbornanone | |
| JPS6148492B2 (en) | ||
| US2966513A (en) | Production of naphthalene dicarboxylic acids | |
| JPH0352881A (en) | Preparation of tetronic alkylate | |
| US5334754A (en) | Process for preparing 2,5-diphenylterephthalic acid by oxidation | |
| Kurita et al. | Diphthalimido carbonate: A new reagent for active ester synthesis | |
| JPH01113341A (en) | Production of methyl carboxylate | |
| JPH03130247A (en) | Production of aromatic carboxylic acid | |
| JPH026412A (en) | Method for production of a carboxylic acid halide | |
| JPS5949213B2 (en) | Method for producing aromatic dicarboxylic acid | |
| JPS6245859B2 (en) | ||
| JPH01283242A (en) | Tetraacyloxytetralin derivative and production thereof | |
| US5245058A (en) | Preparation of 1-nitroanthraquinone-2-carboxylic acids | |
| JPS61178947A (en) | Manufacture of arylalkyl ketone | |
| WO2001094289A1 (en) | Process for the preparation of bromoisophthalic acid compounds | |
| KR820002063B1 (en) | Process for preparation of chloro benzoic acid | |
| CN117510332A (en) | New method for synthesizing 6, 8-dichloro octanoic acid ester | |
| SU345671A1 (en) | ||
| JPS6310706B2 (en) | ||
| CN116283573A (en) | Method for synthesizing 6-hydroxy-8-chlorooctanoic acid ethyl ester |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |