DD211558A1 - METHOD FOR THE PRODUCTION OF SUBSTITUTED ISOTHIAZOLES - Google Patents
METHOD FOR THE PRODUCTION OF SUBSTITUTED ISOTHIAZOLES Download PDFInfo
- Publication number
- DD211558A1 DD211558A1 DD24499582A DD24499582A DD211558A1 DD 211558 A1 DD211558 A1 DD 211558A1 DD 24499582 A DD24499582 A DD 24499582A DD 24499582 A DD24499582 A DD 24499582A DD 211558 A1 DD211558 A1 DD 211558A1
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- halogen
- isothiazoles
- preparation
- substituted
- general formula
- Prior art date
Links
- 150000003854 isothiazoles Chemical class 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- -1 alkali metal alkoxide Chemical class 0.000 claims abstract description 4
- DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
- 125000003277 amino group Chemical group 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 3
- 229910052740 iodine Inorganic materials 0.000 claims abstract 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 abstract description 3
- 239000002168 alkylating agent Substances 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DTYGPHSXPBJSNQ-UHFFFAOYSA-L disodium 2-cyano-3-oxo-3-phenylprop-1-ene-1,1-dithiolate Chemical compound [Na+].[Na+].[S-]C([S-])=C(C#N)C(=O)c1ccccc1 DTYGPHSXPBJSNQ-UHFFFAOYSA-L 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 150000004662 dithiols Chemical group 0.000 description 1
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
Abstract
Die Erfindung betrifft ein Verfahren zur Herstellung von substituierten Isothiazolen der allgemeinen Formel I, in der R hoch 1 ein Aryl-, Hetaryl- oder Alkylgruppe, R hoch 2 Halogen oder eine Alkylthio- bzw. Aminogruppe und R hoch 3 Halogen oder eine Hydroxy- bzw. Sulfenylaminogruppe bedeuten. Ziel der Erfindung ist die Herstellung neuer, substituierter Isothiazole aus leicht zugaenglichen Ausgangsprodukten. Erfindungsgemaess wird Dinatrium-1-acyl-1-cyan-ethen-2,2-dithiolat mit Wasserstoffperoxid, Natronlauge und einem Alkylierungsmittel oder mit einem Halogen bzw. mit Hydroxylamin-O-sulfonsaeure/Alkalialkoholat umgesetzt. Isothiazole koennen als Zwischenprodukte biologisch aktiver Substanzen verwendet werden.The invention relates to a process for the preparation of substituted isothiazoles of the general formula I, in which R is high, an aryl, hetaryl or alkyl group, R 2 halogen or an alkylthio or amino group and R 3 is halogen or a hydroxy or Sulfenylamino mean. The aim of the invention is the preparation of new, substituted isothiazoles from readily available starting materials. According to the invention, disodium 1-acyl-1-cyano-ethene-2,2-dithiolate is reacted with hydrogen peroxide, sodium hydroxide solution and an alkylating agent or with a halogen or with hydroxylamine-O-sulfonic acid / alkali metal alkoxide. Isothiazoles can be used as intermediates of biologically active substances.
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen substituierten Isothiazolen der allgemeinen Formel I,The invention relates to a process for the preparation of novel substituted isothiazoles of the general formula I
1 21 2
in der R eine Aryl-, Hetaryl- oder Alkylgruupe, R Halogen oder eine Alkylthio- bzw. Aminogruppe und R-^ Halogen oder eine Hydroxy- bzw. SuIfenylaainogruppe bedeuten· Substituierte Isothiazole können als Zwischenprodukte für die Herstellung biologisch aktiver Substanzen verwendet werden.in which R is an aryl, hetaryl or alkyl group, R is halogen or an alkylthio or amino group and R 1 is halogen or a hydroxy or sulfonylamino group. Substituted isothiazoles can be used as intermediates for the preparation of biologically active substances.
Derartig substituierte Isothiazole sind bisher noch nicht beschrieben worden. Die Synthese der als Ausgangssubstanzen verwendeten Dinatriumsalze geminaler Dithiole ist vom Prinzip her bekannt [w.-D. Rudorf u. M. Augustin, Z. Chem. 22, 255 (1982)]· Ihre Umsetzung mit bestimmten Alkylierungsmitteln führt zu Keten-S,S-acetalen, die wiederum Schlüsselsubstanzen für Heterocyclensynth.esen sind. Auf diesem Wege sind Isothiazole jedoch nicht zugänglich.Such substituted isothiazoles have not yet been described. The synthesis of the disodium salts of geminal dithiols used as starting substances is known in principle [W.-D. Rudorf u. M. Augustin, Z. Chem. 22, 255 (1982)]. Their reaction with certain alkylating agents leads to ketene S, S-acetals, which in turn are key substances for heterocyclic synthases. However, isothiazoles are not accessible in this way.
Ziel der Erfindung sind neue, substituierte. Isothiazole, die auf der Basis von leicht zugänglichen Ausgangsprodukten hergestellt werden.The aim of the invention are new, substituted. Isothiazoles, which are prepared on the basis of readily available starting materials.
Der Erfindung liegt die Aufgabe zugrunde, diese neuen Verbindungen nach einem einfachen Verfahren herzustellen.The invention has for its object to produce these new compounds according to a simple method.
Srfindungsgemäß werden substituierte Isothiazole der allgemeinen Formel I hergestellt durch Umsetzung von Dinatrium-1-acyl-1-cyan-ethen-2,2-dithiolat der allgemeinen "Formel II, in der R die gleiche Bedeutung wie in Formel i hat,According to the invention, substituted isothiazoles of the general formula I are prepared by reacting disodium 1-acyl-1-cyano-ethene-2,2-dithiolate of the general formula II, in which R has the same meaning as in formula I,
a) mit Wasserstoffperoxid, Natronlauge und einem Alkylierungsmittel,a) with hydrogen peroxide, sodium hydroxide solution and an alkylating agent,
b) mit einem Halogen, wie zum Beispiel Chlor oder Brom, oderb) with a halogen, such as chlorine or bromine, or
c) mit Hydroxylamin-O-sulfonsäure in Gegenwart eines Alkalialkoholats unter Erwärmen.c) with hydroxylamine-O-sulfonic acid in the presence of an alkali metal alcoholate with heating.
Es war überraschend und nicht zu erwarten, daß sich das Dinatrium-1-acyl-1-cyanethen-2,2-dithiolat so leicht in Iso- ' thiazole überführen läßt.It was surprising and not expected that the disodium 1-acyl-1-cyanethene-2,2-dithiolate can be converted so easily into iso-thiazoles.
Das erfindungsgemäße Verfahren wird durch die Gleichungen 1 bis 3 veranschaulicht.The process according to the invention is illustrated by Equations 1 to 3.
^-Benzoyl-5-hydrosy-3-methylthio-isothiazol^ Benzoyl-5-hydrosy-3-methylthio-isothiazole
5»30 g Dinatrium-1-benzoyl-1-cyan-ethen-2,2-dithiolat werden in 45 ml Wasser gelöst. Unter Rühren und mäßiger Kühlung wird mit 25 ml 4 %iger HpOn-Lösung versetzt. Zur Vervollstän-5 »Dissolve 30 g of disodium 1-benzoyl-1-cyano-ethene-2,2-dithiolate in 45 ml of water. With stirring and moderate cooling, 25 ml of 4% HpOn solution are added. To complete
digung der Reaktion rührt man noch, einige Zeit bei Raumtemperatur. Dann wird in 300 ml Eiswasser gegeben und leicht angesäuert. Die ausgefallenen gelben Kristalle werden abgesaugt und in 37,5 ml 2,5 η NaOH unter Rühren gelöst. Fach 15 ™i-n gibt man 1,9 S Dimethylsulfat hinzu. Es wird eine weitere Stunde bei Raumtemperatur gerührt. Man läßt über Nacht stehen, saugt den Niederschlag ab und extrahiert das illtrat zweimal mit je 75 ml Chloroform. Die eingeengten Extrakte werden mit 350 ml Wasser verdünnt und mit Salzsäure vorsichtig angesäuertThe reaction is still stirred for a while at room temperature. It is then poured into 300 ml of ice-water and slightly acidified. The precipitated yellow crystals are filtered off and dissolved in 37.5 ml of 2.5 N NaOH with stirring. Box 15 ™ i n one gives 1.9 added S dimethyl sulfate. It is stirred for a further hour at room temperature. It is allowed to stand overnight, the precipitate is filtered off with suction and extracted the illtrat twice with 75 ml of chloroform. The concentrated extracts are diluted with 350 ml of water and carefully acidified with hydrochloric acid
5p. = 192-194 0G (Aceton), Ausbeute 42 %.5p. = 192-194 0 G (acetone), yield 42%.
4-Benzoyl-3,5-<äichlor-isothiazol4-benzoyl-3,5 <äichlor-isothiazole
5,30 g Dinatrium-1-benzoyl-1-cyan-ethen-2,2-dithiolat werden in 140 ml abs. Tetrachlorkohlenstoff gelöst. Ss wird unter Rückfluß zum Sieden erhitzt und 2 h Chlor eingeleitet. Nach Beendigung der Gaszufuhr wird abgekühlt und'filtriert. Man engt das illtrat ein und bringt das resultierende öl durch Zugabe von Petrolether zur Kristallisation. Fp. = 180-183 0C (MeOH), Ausbeute 24 %. 5.30 g of disodium 1-benzoyl-1-cyano-ethene-2,2-dithiolate are dissolved in 140 ml of abs. Carbon tetrachloride dissolved. The mixture is heated to boiling under reflux and chlorine is introduced for 2 h. After completion of the gas supply is cooled and'filtriert. The illtrate is concentrated and the resulting oil is crystallized by addition of petroleum ether. Mp. = 180-183 0 C (MeOH), yield 24%.
3-Amino-4-benzoyl-5-sulfenylamino-isothiazol3-Amino-4-benzoyl-5-sulfenylamino-isothiazol
5,30 g Dinatrium-1-benzoyl-1-cyan-ethen-2,2-dithiolat werden in 50 ml Ethanol gelöst. Es werden 10 ml ethanolische Natriumethylatlösung hinzugegeben und dann 6 g Hydroxylamin-0-sulfonsäure (in 13Ο ml Wasser gelöst) zugetropft. Man erwärmt 2 h auf 50 0C und rührt noch 16 h bei Raumtemperatur. Die ausgefallenen Kristalle werden abgesaugt, mit Ethanol gewaschen, das Piltrat eingeengt und das resultierende öl mit Aceton zur Kristallisation gebracht5.30 g of disodium 1-benzoyl-1-cyano-ethene-2,2-dithiolate are dissolved in 50 ml of ethanol. There are added 10 ml of ethanolic Natriumethylatlösung and then 6 g of hydroxylamine-0-sulfonic acid (dissolved in 13Ο ml of water) was added dropwise. The mixture is heated for 2 h at 50 0 C and stirred for 16 h at room temperature. The precipitated crystals are filtered off with suction, washed with ethanol, the filtrate is concentrated and the resulting oil is crystallized with acetone
Pp. = 273-276 0C (Aceton), Ausbeute 15 %.Pp. 273-276 = 0 C (acetone), yield 15%.
Hierzu 1 Seite Ponneln.For this purpose 1 side piling.
IfIf
I ·I ·
R2 R 2
Gleichung 1:Equation 1:
R1-GO^ ^SNa 1. H2O2. 2. HaOH R1-C0q --^-SGH3 R 1 -GO ^ ^ SNa 1.H 2 O 2 . 2. HaOH R 1 -C0q - ^ - SGH 3
1111
S IIS II
Gleichung 2:Equation 2:
II § T ΪΓII § T ΪΓ
ΊΓΊΓ
/Ti 1^1/ Ti 1 ^ 1
l,j .L '— ^Sl, j .L '- ^ S
Gleichung 3JEquation 3J
+ 2 H0U-OSOoH R1-GO-, π—HS.+ 2 H 0 U-OSOoH R 1 -GO-, π-HS.
II ^-_—^ ^II ^ -_- ^ ^
(pH>7)(PH> 7)
-♦ ο unu man*c\r, Qtzrtη - ♦ unu man * c \ r, Qtzrtη
Claims (2)
oder Alky!gruppe, R Halogen oder eine Alkylthio- bzw.2
or Alky! group, R is halogen or an alkylthio or
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD24499582A DD211558A1 (en) | 1982-11-18 | 1982-11-18 | METHOD FOR THE PRODUCTION OF SUBSTITUTED ISOTHIAZOLES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD24499582A DD211558A1 (en) | 1982-11-18 | 1982-11-18 | METHOD FOR THE PRODUCTION OF SUBSTITUTED ISOTHIAZOLES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD211558A1 true DD211558A1 (en) | 1984-07-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD24499582A DD211558A1 (en) | 1982-11-18 | 1982-11-18 | METHOD FOR THE PRODUCTION OF SUBSTITUTED ISOTHIAZOLES |
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| Country | Link |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997038987A1 (en) * | 1996-04-16 | 1997-10-23 | Basf Aktiengesellschaft | Herbicidal benzoylisothiazoles |
-
1982
- 1982-11-18 DD DD24499582A patent/DD211558A1/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997038987A1 (en) * | 1996-04-16 | 1997-10-23 | Basf Aktiengesellschaft | Herbicidal benzoylisothiazoles |
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