CA1264472A - Process for the production of thiotetronic acid - Google Patents
Process for the production of thiotetronic acidInfo
- Publication number
- CA1264472A CA1264472A CA000499621A CA499621A CA1264472A CA 1264472 A CA1264472 A CA 1264472A CA 000499621 A CA000499621 A CA 000499621A CA 499621 A CA499621 A CA 499621A CA 1264472 A CA1264472 A CA 1264472A
- Authority
- CA
- Canada
- Prior art keywords
- acid
- amine
- thiotetronic
- chloro
- thiotetronic acid
- 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/32—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epoxy Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
A process is disclosed for the production of thio-tetronic acid, in which 4-chloro-4-chloromethyloxetan-2-one is reacted directly with hydrogen sulfide in the presence of an amine to produce thiotetronic acid. Alternatively, the reaction mixture is converted prior to isolation of the thiotetronic acid with ketene and the conversion product is converted with a mineral acid in order to obtain the thiotetronic acid.
A process is disclosed for the production of thio-tetronic acid, in which 4-chloro-4-chloromethyloxetan-2-one is reacted directly with hydrogen sulfide in the presence of an amine to produce thiotetronic acid. Alternatively, the reaction mixture is converted prior to isolation of the thiotetronic acid with ketene and the conversion product is converted with a mineral acid in order to obtain the thiotetronic acid.
Description
The invention relates-to a process for the production of thiotetronic acid.
It has been reported that thiotetronic acid m~y posess utility as an intermedlate product Eor the production of l~) thiolact~cin, whLch is an c~ntibiotic having a broad effective spectnm. T rahedron Letters, Vol. 25, No. 46, pp 5243-to 5246, (1984). From senary~ Chem.
Berichte 46, 2103, (1913)j it is known to produce thiotetronic acid star-ting from acetyl thioglycoyl chloride through reac-tion thereof wlth sodium malonlc ester and subsequent ring closure and water treatment. D.B. Macierewicz, Rocz. Chem.
47, 1735, (1973), reproduced the reaction of E. Benary and ob-tained thiotetronic acid in a yield of 30.3 percent, based on the ace-tyl-thioglycoyl chloride used. Another possibility ~ for synthesis is set out in J.Z.: Mortensen et al., Tetrahedron .~ 15 Letters) 27, 3839 (1971~. Starting from 2,4-dibromothiophene, the thiotetronic acid i5 obtained in a yield of 46.2 percent by way of three s-teps as a result of reaction with bu-tyl .~ lithium and t-butylperbenzoate.
~; However, in the case of all of the above-identified ~ 20 traditional syntheses, the yields are much too low for a technical or commercial process. Moreover, the processes are characterized by cumbersomeness, expensive educts and ~ by reagents that are difficult to handle.
: An object of the invention is to provide a process for the production of thiotetronic acid which is distinguished by high yields and high purity of thiotetronic acid, favorable educts and simple procedural steps.
~ccordingly, the invention provides a process t~ -~<1 , ' 1~ 64~7~
It has been reported that thiotetronic acid m~y posess utility as an intermedlate product Eor the production of l~) thiolact~cin, whLch is an c~ntibiotic having a broad effective spectnm. T rahedron Letters, Vol. 25, No. 46, pp 5243-to 5246, (1984). From senary~ Chem.
Berichte 46, 2103, (1913)j it is known to produce thiotetronic acid star-ting from acetyl thioglycoyl chloride through reac-tion thereof wlth sodium malonlc ester and subsequent ring closure and water treatment. D.B. Macierewicz, Rocz. Chem.
47, 1735, (1973), reproduced the reaction of E. Benary and ob-tained thiotetronic acid in a yield of 30.3 percent, based on the ace-tyl-thioglycoyl chloride used. Another possibility ~ for synthesis is set out in J.Z.: Mortensen et al., Tetrahedron .~ 15 Letters) 27, 3839 (1971~. Starting from 2,4-dibromothiophene, the thiotetronic acid i5 obtained in a yield of 46.2 percent by way of three s-teps as a result of reaction with bu-tyl .~ lithium and t-butylperbenzoate.
~; However, in the case of all of the above-identified ~ 20 traditional syntheses, the yields are much too low for a technical or commercial process. Moreover, the processes are characterized by cumbersomeness, expensive educts and ~ by reagents that are difficult to handle.
: An object of the invention is to provide a process for the production of thiotetronic acid which is distinguished by high yields and high purity of thiotetronic acid, favorable educts and simple procedural steps.
~ccordingly, the invention provides a process t~ -~<1 , ' 1~ 64~7~
- 2 -for preparing thiote-tronic acid/ in which 4-chloro-4-chloro-methyloxetan-2-one is reacted with hydrogen sulfidè in the presence of an amine to form thiotetronic acid directly, or, alternatively, -the reaction solution is reacted prior to isola-tion of the thiotetronic acid with ke-tene, the result-ant diacetoxythiophene i5 separated and the diacetoxythiophene is flnally converted into thiotetronic acid using mineral acid.
Another aspect of the invention comprises the novel in-termediate product diacetoxythiophene, having the formuIa: CH3-C~
~ O-~-CH
S
-;~ 15 The 4-chloro-4-chloromethyloxe-tan-2-one starting material can be produced in a simple manner according to published European Patent Application 60~808 and after flash distillation can be used for the conversion according to the invention.
The hydrogen sulfide is conveniently used in gaseous .
form.
; As suitable amines, advantageously primary, secondary or tertiary amines, ammonia and also guanidine can be used.
Tertiary amines, such as triethylamine, are particularly advantageous.
The reaction is conveniently carried out in a solvent or solvents. As compared to the reactive educt, ~,' i4~2 inert solvents such as halogenated hydrocarbons, ether or carboxylic acid esters are used. For example, methylene chloride, chloroform, ethereal solvents, such ac, tetra-hydrofuran, and also acetic acid ester can be used. ParticuS larly preferred, ~lowever, as the solvent is tetrahydrofuran.
The educts are used effectively in a mole ratio of 4-chloro-4-chloromethyloxetan-2-one -to hydrogen sulfide to amine of from 1~ 2 to 1:4:3, and preferably between 2.5:2 and 1-3.5:2.5.
Preferably the reaction lS operated at a temperature of from 0 to -~0C., m~re preferably between -10 and -25C.
Effectively, the method proceeds in such a way that the educt solution is saturated with the hydrogen sulfide and the amine is added subsequently over a period of 30 to 120 minutes.
After complete addition of the amine, the processing of the -thiotetronic acid can take place by filtering off the precipitated salt and ~ubsequently concentrating the solu-tion. For the separation of small quan-tities of dimeric anhydrothiotetronic acid, the residue can be absorbed in ethereal solvents, such as diethyl ether, tetrahydrofuran (THF) or dioxane, preferably in diethyl ether, and can be filtered by way of an absorption agent, such as silica gel.
After renewed concentration by evaporation of the solvent, the thiotetronic acid is ob-tained in crys-talline form and in good yield.
After recrystallization in an aromatic hydrocarbon, i , \
, : ' .
3L~6~7~
preferably in toluene, the thiotetronic acid is subjected -to additional purification.
In order to obtain a -thio-te-tronic acid of good quality, -the method can proceed in such a way that, af-ter the addi-tion of the amine, wi-thout isolation of the crude thiotetronic acid, the lat-ter is -treat~d in solution with ketene at a temperature of -lO to +5C., advantageously 0C. Based on one mole of 4-chloro-4-chloromethyloxe-tan-2-one used, ketene is effectively used in a quantity of 2 to 4 moles, preferably 2.5 to 3.5 moles.
; In the course of the process according to the invention, the novel intermediate compound 2,4-diacetoxy-thiophene having the formula: RO
~ O~
', O
wherein each R is CH3C-, results. The 2,4-diacetoxythiophene can also be purified by distil1ation in a simple manner.
By treatlng the 2,4-diacetoxythiophene with a non-oxidizing inorganic mineral acidr pure thiotetronic acid is obtained. Hydrochloric acid or sulfuric acid, preferably hydrochloric acid, can be used in aqueous solu-tion in a concentration of lO to 30 percent. The conversion temperature is generally between 0 ana 30C., preferably ; 25 15 to 25C. The reaction time can be 2 to 5 hours.
After concentration, preferably using high vacuum, this procedure provides practically colorless thiotetronio ;~;
,`, ''"' ~
`
~264472 -- 5 ~
acid in high yield with a purity greater than 96 percent.
As used herein, all par-ts, percen-tages, ratios and proportlons are on a weiyht basis unless otherwise s-tated hereLn or o-therwise obvious herefrom to one skilled in the art.
The following Examples illustxate the invention.
EXhMPLE i 15~5 g (0.091 mole) of 4-chloro-4-chloromethyloxe-tan-2-one was co~l~ed to -20C~ in 300 ml of tetrahydrofurane and was satu~a-ted with gaseous hydrogen sulfide. Subsequently, a solution of 20~2 g (0.2 mole) of triethylamine in 100 ml of tetrahydrofuran was added dropwise at -15C. ov~
a period of one hour~ The temperature of the reaction solu-tion was allowed to rise to ambien-t temperature, the solution ; 15 was filtered off from the salt obtained and the solvent -~ was evaporated on a rotation evaporator. The residue was flltered thr~ugh a column filled with silica gel, using 300 ml of ether as eluent~ 9~0 g of a yellow colored crystal-line product having a melting point of I15 to 117C~ was obtained. The content (HPLC) amounted to 89.3 percent.
This corresponds to 8.0 g of lOO percent product = 75~7 percent yield. 7~5 g of the crude thiotetxonic acid was recrystallized hot from 350 ml of toluene. 6.6. g of pale rose-colored microcrystalline product having a melting point of 120C and a content ~HPLC) of 96 percen-t was ob-tained.
This corresponded to 6.3 g of 100 percent produc-t - 94 percent yield or 71~2 percent based on the oxe-tanone used~
. ~
~64~
Thio-te-tronic acid was produced as described in Example 1. However, the thiotetronic acid was no-t i.solated but -the -te-trahydrofuran (THF) solution was concentrated to 50 ml and over a period of one hour 0.3 mole of ketene was fed in-to this solu-tion ak O~C. Subsequently,~-the temperature of the reac-tion so.lution was allowed.to rise to ambient temperature and the solvent was distilled.off using a ro-tation evaporator. The residue was subjected to high vacuum distilla-tion. 13.7 g of 2,4-diacetoxythiophene was obtained, content 95.6 percent, b.p.o 25 105C., which corresponded -to 13.1 g of lOO:percent produc-t ~yield 65.2 " percent)~
Spectroscopic data:
H-NMR~300 MHz, CDCL3): ~2.24(s,3H), 2.30(s,3H?, 6.57~d,J=
~ 15 2.5Hz,lH?, 6.61 (d,lH) - ` MS(70eV) m/2=200(M ,3), 158(M -CH2=C=O,10~ 116 ~M -2 . ~
.. . .
: ~ CH2=C=O,35) 43 (100) 1.81 g of the 2,4-diacetoxythiophene was reacted with 3~5 g of 20 percent hydrochloric acia and the mixture ~ 20 was stirred at am~ient temperature ~or 3 hours. After 1 : hour, a clear solu~ion developed from the initial emulsion.
- ThiS colored solution~was evaporated under high vacuum.
~ l.O.g of practically colorless crystalline product was :, ~ obtained hav.tng a melting point of 119 to 121C.. :(HPLC
:~ 25 con-tent: 96.1 percent). This corresponded to 0.96 g of 100.percent -thiotetronlc acid = 96 percent yield.
~ '' .. ~. ;,., ' : -~X~4~
By way of summaryl the invention involves a process for the produc-tion of thiotetronic acid by the reaction 4-chloro-4-chloromethyloxe-tan-2-one and hydrogen sulfide in the presence of an amine.
~. ~
"~
'.
~ 15 -;~
i 20 ,~:
'': : ~ :
:::
~' :' ~ ' ..
~ ~ ., ' .
Another aspect of the invention comprises the novel in-termediate product diacetoxythiophene, having the formuIa: CH3-C~
~ O-~-CH
S
-;~ 15 The 4-chloro-4-chloromethyloxe-tan-2-one starting material can be produced in a simple manner according to published European Patent Application 60~808 and after flash distillation can be used for the conversion according to the invention.
The hydrogen sulfide is conveniently used in gaseous .
form.
; As suitable amines, advantageously primary, secondary or tertiary amines, ammonia and also guanidine can be used.
Tertiary amines, such as triethylamine, are particularly advantageous.
The reaction is conveniently carried out in a solvent or solvents. As compared to the reactive educt, ~,' i4~2 inert solvents such as halogenated hydrocarbons, ether or carboxylic acid esters are used. For example, methylene chloride, chloroform, ethereal solvents, such ac, tetra-hydrofuran, and also acetic acid ester can be used. ParticuS larly preferred, ~lowever, as the solvent is tetrahydrofuran.
The educts are used effectively in a mole ratio of 4-chloro-4-chloromethyloxetan-2-one -to hydrogen sulfide to amine of from 1~ 2 to 1:4:3, and preferably between 2.5:2 and 1-3.5:2.5.
Preferably the reaction lS operated at a temperature of from 0 to -~0C., m~re preferably between -10 and -25C.
Effectively, the method proceeds in such a way that the educt solution is saturated with the hydrogen sulfide and the amine is added subsequently over a period of 30 to 120 minutes.
After complete addition of the amine, the processing of the -thiotetronic acid can take place by filtering off the precipitated salt and ~ubsequently concentrating the solu-tion. For the separation of small quan-tities of dimeric anhydrothiotetronic acid, the residue can be absorbed in ethereal solvents, such as diethyl ether, tetrahydrofuran (THF) or dioxane, preferably in diethyl ether, and can be filtered by way of an absorption agent, such as silica gel.
After renewed concentration by evaporation of the solvent, the thiotetronic acid is ob-tained in crys-talline form and in good yield.
After recrystallization in an aromatic hydrocarbon, i , \
, : ' .
3L~6~7~
preferably in toluene, the thiotetronic acid is subjected -to additional purification.
In order to obtain a -thio-te-tronic acid of good quality, -the method can proceed in such a way that, af-ter the addi-tion of the amine, wi-thout isolation of the crude thiotetronic acid, the lat-ter is -treat~d in solution with ketene at a temperature of -lO to +5C., advantageously 0C. Based on one mole of 4-chloro-4-chloromethyloxe-tan-2-one used, ketene is effectively used in a quantity of 2 to 4 moles, preferably 2.5 to 3.5 moles.
; In the course of the process according to the invention, the novel intermediate compound 2,4-diacetoxy-thiophene having the formula: RO
~ O~
', O
wherein each R is CH3C-, results. The 2,4-diacetoxythiophene can also be purified by distil1ation in a simple manner.
By treatlng the 2,4-diacetoxythiophene with a non-oxidizing inorganic mineral acidr pure thiotetronic acid is obtained. Hydrochloric acid or sulfuric acid, preferably hydrochloric acid, can be used in aqueous solu-tion in a concentration of lO to 30 percent. The conversion temperature is generally between 0 ana 30C., preferably ; 25 15 to 25C. The reaction time can be 2 to 5 hours.
After concentration, preferably using high vacuum, this procedure provides practically colorless thiotetronio ;~;
,`, ''"' ~
`
~264472 -- 5 ~
acid in high yield with a purity greater than 96 percent.
As used herein, all par-ts, percen-tages, ratios and proportlons are on a weiyht basis unless otherwise s-tated hereLn or o-therwise obvious herefrom to one skilled in the art.
The following Examples illustxate the invention.
EXhMPLE i 15~5 g (0.091 mole) of 4-chloro-4-chloromethyloxe-tan-2-one was co~l~ed to -20C~ in 300 ml of tetrahydrofurane and was satu~a-ted with gaseous hydrogen sulfide. Subsequently, a solution of 20~2 g (0.2 mole) of triethylamine in 100 ml of tetrahydrofuran was added dropwise at -15C. ov~
a period of one hour~ The temperature of the reaction solu-tion was allowed to rise to ambien-t temperature, the solution ; 15 was filtered off from the salt obtained and the solvent -~ was evaporated on a rotation evaporator. The residue was flltered thr~ugh a column filled with silica gel, using 300 ml of ether as eluent~ 9~0 g of a yellow colored crystal-line product having a melting point of I15 to 117C~ was obtained. The content (HPLC) amounted to 89.3 percent.
This corresponds to 8.0 g of lOO percent product = 75~7 percent yield. 7~5 g of the crude thiotetxonic acid was recrystallized hot from 350 ml of toluene. 6.6. g of pale rose-colored microcrystalline product having a melting point of 120C and a content ~HPLC) of 96 percen-t was ob-tained.
This corresponded to 6.3 g of 100 percent produc-t - 94 percent yield or 71~2 percent based on the oxe-tanone used~
. ~
~64~
Thio-te-tronic acid was produced as described in Example 1. However, the thiotetronic acid was no-t i.solated but -the -te-trahydrofuran (THF) solution was concentrated to 50 ml and over a period of one hour 0.3 mole of ketene was fed in-to this solu-tion ak O~C. Subsequently,~-the temperature of the reac-tion so.lution was allowed.to rise to ambient temperature and the solvent was distilled.off using a ro-tation evaporator. The residue was subjected to high vacuum distilla-tion. 13.7 g of 2,4-diacetoxythiophene was obtained, content 95.6 percent, b.p.o 25 105C., which corresponded -to 13.1 g of lOO:percent produc-t ~yield 65.2 " percent)~
Spectroscopic data:
H-NMR~300 MHz, CDCL3): ~2.24(s,3H), 2.30(s,3H?, 6.57~d,J=
~ 15 2.5Hz,lH?, 6.61 (d,lH) - ` MS(70eV) m/2=200(M ,3), 158(M -CH2=C=O,10~ 116 ~M -2 . ~
.. . .
: ~ CH2=C=O,35) 43 (100) 1.81 g of the 2,4-diacetoxythiophene was reacted with 3~5 g of 20 percent hydrochloric acia and the mixture ~ 20 was stirred at am~ient temperature ~or 3 hours. After 1 : hour, a clear solu~ion developed from the initial emulsion.
- ThiS colored solution~was evaporated under high vacuum.
~ l.O.g of practically colorless crystalline product was :, ~ obtained hav.tng a melting point of 119 to 121C.. :(HPLC
:~ 25 con-tent: 96.1 percent). This corresponded to 0.96 g of 100.percent -thiotetronlc acid = 96 percent yield.
~ '' .. ~. ;,., ' : -~X~4~
By way of summaryl the invention involves a process for the produc-tion of thiotetronic acid by the reaction 4-chloro-4-chloromethyloxe-tan-2-one and hydrogen sulfide in the presence of an amine.
~. ~
"~
'.
~ 15 -;~
i 20 ,~:
'': : ~ :
:::
~' :' ~ ' ..
~ ~ ., ' .
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the production of thiotetronic acid, comprising reacting 4-chloro-4-chloromethyloxetan-2-one with hydrogen sulfide in the presence of an amine to provide the thiotetronic acid directly, or alternatively treating the reaction mixture, prior to isolation of the thiotetronic acid, with ketene and treating the resulting product with mineral acid in order to obtain the thiotetronic acid.
2. A process as claimed in Claim 1, wherein the amine is a primary amine, a secondary amine, a tertiary amine, ammonia or guanidine.
3. A process as claimed in Claim 2, wherein the amine is a tertiary amine.
4. A process as claimed in Claim 1, 2 or 3, wherein the reaction is carried out in an inert solvent,
5. A process as claimed in Claim 1, 2 or 3, wherein the educt ratio of 4-chloro-4-chloromethyloxetan-2-one to hydrogen sulfide to amine is from 1:2:2 to 1:4:3.
6. A process as claimed in Claim 1, 2 or 3, wherein the reaction temperature is from 0° to -40°C.
7. A process as claimed in Claim 1, 2 or 3, wherein the ketene is used in a quantity of from 2 to 4 moles per mole of 4-chloro-4-chloromethyloxetan-2-one.
8. A process as clalmed in Claim 1, 2 or 3, wherein the mineral acid is a non-oxidizing mineral acid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH192/85A CH663206A5 (en) | 1985-01-16 | 1985-01-16 | METHOD FOR PRODUCING THIOTETRONIC ACID. |
| CHGES.192/85 | 1985-01-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1264472A true CA1264472A (en) | 1990-01-16 |
Family
ID=4181346
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000499621A Expired - Fee Related CA1264472A (en) | 1985-01-16 | 1986-01-15 | Process for the production of thiotetronic acid |
| CA000602707A Expired - Fee Related CA1267905A (en) | 1985-01-16 | 1989-06-13 | Thiophene derivative |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000602707A Expired - Fee Related CA1267905A (en) | 1985-01-16 | 1989-06-13 | Thiophene derivative |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0189096B1 (en) |
| JP (1) | JPS6236375A (en) |
| AT (1) | ATE41929T1 (en) |
| CA (2) | CA1264472A (en) |
| CH (1) | CH663206A5 (en) |
| DE (1) | DE3662688D1 (en) |
| DK (2) | DK162766C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7417150B2 (en) | 2001-04-20 | 2008-08-26 | Bayer Cropscience Ag | Azoles having an insecticidal action |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH667655A5 (en) * | 1986-09-24 | 1988-10-31 | Lonza Ag | METHOD FOR PRODUCING 4-ALKOXY-2 (5H) THIOPHENONES. |
-
1985
- 1985-01-16 CH CH192/85A patent/CH663206A5/en not_active IP Right Cessation
-
1986
- 1986-01-09 JP JP61002839A patent/JPS6236375A/en active Pending
- 1986-01-14 DE DE8686100424T patent/DE3662688D1/en not_active Expired
- 1986-01-14 EP EP86100424A patent/EP0189096B1/en not_active Expired
- 1986-01-14 AT AT86100424T patent/ATE41929T1/en not_active IP Right Cessation
- 1986-01-15 DK DK017886A patent/DK162766C/en not_active IP Right Cessation
- 1986-01-15 CA CA000499621A patent/CA1264472A/en not_active Expired - Fee Related
-
1989
- 1989-06-13 CA CA000602707A patent/CA1267905A/en not_active Expired - Fee Related
-
1991
- 1991-03-27 DK DK056391A patent/DK162642C/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7417150B2 (en) | 2001-04-20 | 2008-08-26 | Bayer Cropscience Ag | Azoles having an insecticidal action |
Also Published As
| Publication number | Publication date |
|---|---|
| DK17886A (en) | 1986-07-17 |
| ATE41929T1 (en) | 1989-04-15 |
| CA1267905A (en) | 1990-04-17 |
| DK162642C (en) | 1992-04-13 |
| DK56391D0 (en) | 1991-03-27 |
| DK56391A (en) | 1991-03-27 |
| EP0189096A1 (en) | 1986-07-30 |
| DE3662688D1 (en) | 1989-05-11 |
| DK162642B (en) | 1991-11-25 |
| DK162766B (en) | 1991-12-09 |
| DK162766C (en) | 1992-04-27 |
| JPS6236375A (en) | 1987-02-17 |
| CH663206A5 (en) | 1987-11-30 |
| DK17886D0 (en) | 1986-01-15 |
| EP0189096B1 (en) | 1989-04-05 |
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