DE1187625B - Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives - Google Patents

Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives

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Publication number
DE1187625B
DE1187625B DEH36993A DEH0036993A DE1187625B DE 1187625 B DE1187625 B DE 1187625B DE H36993 A DEH36993 A DE H36993A DE H0036993 A DEH0036993 A DE H0036993A DE 1187625 B DE1187625 B DE 1187625B
Authority
DE
Germany
Prior art keywords
benzothiadiazine
preparation
dioxide derivatives
general formula
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.)
Pending
Application number
DEH36993A
Other languages
German (de)
Inventor
Dr Rer Nat Rudolf Fried
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
HAURY CHEM FAB DR HEINZ
Original Assignee
HAURY CHEM FAB DR HEINZ
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by HAURY CHEM FAB DR HEINZ filed Critical HAURY CHEM FAB DR HEINZ
Priority to DEH36993A priority Critical patent/DE1187625B/en
Priority to CH601060A priority patent/CH388972A/en
Publication of DE1187625B publication Critical patent/DE1187625B/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/15—Six-membered rings
    • C07D285/16—Thiadiazines; Hydrogenated thiadiazines
    • C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
    • C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
    • C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
    • C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
    • C07D285/28—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3

Description

Verfahren zur Herstellung von I ,2,4-Benzothiadiazin- 1, l-dioxydderivaten Die Erfindung betrifft ein Verfahren zur Herstellung von 1,2,4-Benzothiadiazin- 1, dioxydderivaten der allgemeinen Formel worin R ein Halogenatom oder einen Trihalogenmethylrest und n die Zahl 0 oder 1 bedeutet, das darin besteht, daß man 2 Mol eines 2,4~Disulfamylanilins der allgemeinen Formel in der R die oben angegebene Bedeutung hat, bei erhöhter Temperatur mit 1 bis 2 Mol Oxalsäure oder Malonsäure oder deren Estern oder Säurehalogeniden umsetzt.Process for the preparation of 1,2,4-benzothiadiazine-1, l-dioxide derivatives The invention relates to a process for the preparation of 1,2,4-benzothiadiazine-1, dioxide derivatives of the general formula wherein R is a halogen atom or a trihalomethyl radical and n is the number 0 or 1, which consists in that 2 mol of a 2,4-disulfamylaniline of the general formula in which R has the meaning given above, is reacted at an elevated temperature with 1 to 2 moles of oxalic acid or malonic acid or their esters or acid halides.

Die Umsetzung von 2,4-Disulfamyl-5-halogenanilinen mit einer Monocarbonsäure, z. B. Ameisensäure, zu Verbindungen der allgemeinen Formel ist schon in der USA.-Patentschrift 2 809 194 beschrieben worden.The reaction of 2,4-disulfamyl-5-haloanilines with a monocarboxylic acid, e.g. B. formic acid, to compounds of the general formula has already been described in U.S. Pat. No. 2,809,194.

Es wurde nun gefunden, daß die erfindungsgemäß herstellbaren Verbindungen eine erhöhte diuretische und blutdrucksenkende Wirkung haben (vgl. die Tabelle). Dosis, Dosis, die zur Erzielung Substanz I des gleichen diuredschen Effekts benötigt wird mgtkgMaus Cl CH / benötigt C-H 500 H2N - OzS H O2 6-Chlor-7-suffamyl- 1 ,2,4benzothiadiazin- 1,1 -dioxyd (USA.-Patentschrift 2 809 194) Fortsetzung Dosis, die zur ErYiehmg descadiu Subsunz | F.ffths benöti¢ winl Enba1öflgtwiixi ngkgMaus C1I:yg 1 75 HiN02S /NIiHN\s/SoNH2 (>2 02 (Beispiele 1 und 2) )NS½$NH2 HjN - ob 02 (Beispiel 3; Fp. 229°() Um die Erfindung noch näher zu erläutern, seien folgende Beispiele gebracht.It has now been found that the compounds which can be prepared according to the invention have an increased diuretic and antihypertensive effect (cf. the table). Dose, dose needed to achieve Substance I of the same diuredschen Effect is needed mgtkgMaus Cl CH / requires CH 500 H2N - OzS H O2 6-chloro-7-suffamyl-1, 2,4benzothiadiazine-1,1-dioxide (U.S. Patent 2,809,194) continuation Dose necessary for ErYiehmg descadiu Subsunz | F.ffths need ¢ winl Enba1öflgtwiixi ngkgMaus C1I: yg 1 75 HiN02S / NIiHN \ s / SoNH2 (> 2 02 (Examples 1 and 2) ) NS½ $ NH2 HjN - whether 02 (Example 3; mp. 229 ° () In order to explain the invention in more detail, the following examples are given.

Beispiel 1 10,0 g 5-Chlor-2,4-disulfamylanilin werden mit 3,0 g Malonsäuredimethylester angerührt und auf dem Elbad 30 Minuten auf 170 bis 1800C erhitzt. Example 1 10.0 g of 5-chloro-2,4-disulfamylaniline are mixed with 3.0 g of dimethyl malonate stirred and heated on the Elbad for 30 minutes to 170 to 1800C.

Der überschüssige Ester wird im Vakuum abdestilliert und der Rückstand aus Alkohol-Wasser (1:1) umkristallisiert. Ausbeute: 8,4 g dreieckige Kristalle; F. 340 bis 345"C. The excess ester is distilled off in vacuo and the residue recrystallized from alcohol-water (1: 1). Yield: 8.4 g of triangular crystals; F. 340 to 345 "C.

Beispiel 2 10,0 g 5-Chlor-2,4-disulfamylanilin werden zu 3,5 g Malonylchlorid in 150 ml Dioxan gegeben und 30 Minuten am Rückfluß erhitzt. Das Lösungsmittel und das überschüssige Malonylchlorid werden im Vakuum entfernt und der Rückstand aus Alkohol-Wasser (1:1) umkristallisiert. Ausbeute: 8,6 g; F. 340 bis 345"C. Example 2 10.0 g of 5-chloro-2,4-disulfamylaniline become 3.5 g of malonyl chloride given in 150 ml of dioxane and heated under reflux for 30 minutes. The solvent and the excess malonyl chloride is removed in vacuo and the residue is removed Recrystallized alcohol-water (1: 1). Yield: 8.6 g; F. 340 to 345 "C.

Beispiel 3 5,0 g 5-Chlor-2,4-disulfamylanilin und 1,5 g Oxalsäure werden in 60 mol Thionylchlorid suspendiert und 4 Stunden am Rückfluß erhitzt, wobei HClas entweicht. Nach dem Erkalten wird filtriert und der Rückstand mit Alkohol extrahiert. Es bleiben 1,4 g alkoholunlösliche Substanz; F. 340"C. Aus dem alkoholischen Extrakt erhält man beim Einengen 2,9 g Kristalle vom F.229"C. Example 3 5.0 g of 5-chloro-2,4-disulfamylaniline and 1.5 g of oxalic acid are suspended in 60 mol of thionyl chloride and refluxed for 4 hours, wherein HClas escapes. After cooling, it is filtered and the residue with alcohol extracted. 1.4 g of alcohol-insoluble substance remain; F. 340 "C. From the alcoholic 2.9 g of crystals of F.229 "C" are obtained on concentration.

Claims (1)

Patentanspruch: Verfahren zur Herstellung von 1 ,2,4-Benzothiadiazin-l 1 -dioxydderivaten der allgemeinen Formel worin R ein Halogenatom oder einen TrihalogenmethyIrest und n die Zahl 0 oder 1 bedeutet, dadurch gekennzeichnet, daß man 2 Mol eines 2,4-Disulfamylanilins der allgemeinen Formel in der R die oben angegebene Bedeutung hat, bei erhöhter Temperatur mit 1 bis 2 Mol Oxalsäure oder Malonsäure oder deren Estern oder Säurehalogeniden umsetzt.Claim: Process for the preparation of 1, 2,4-benzothiadiazine-l 1 -dioxide derivatives of the general formula in which R is a halogen atom or a trihalomethyl radical and n is the number 0 or 1, characterized in that 2 mol of a 2,4-disulfamylaniline of the general formula in which R has the meaning given above, is reacted at an elevated temperature with 1 to 2 moles of oxalic acid or malonic acid or their esters or acid halides. In Betracht gezogene Druckschriften: USA.-Patentschrift Nr. 2 809 194. References considered: U.S. Patent No. 2,809 194.
DEH36993A 1959-07-22 1959-07-22 Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives Pending DE1187625B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DEH36993A DE1187625B (en) 1959-07-22 1959-07-22 Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives
CH601060A CH388972A (en) 1959-07-22 1960-05-25 Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxide derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DEH36993A DE1187625B (en) 1959-07-22 1959-07-22 Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives

Publications (1)

Publication Number Publication Date
DE1187625B true DE1187625B (en) 1965-02-25

Family

ID=7153178

Family Applications (1)

Application Number Title Priority Date Filing Date
DEH36993A Pending DE1187625B (en) 1959-07-22 1959-07-22 Process for the preparation of 1, 2, 4-benzothiadiazine-1, 1-dioxide derivatives

Country Status (2)

Country Link
CH (1) CH388972A (en)
DE (1) DE1187625B (en)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2809194A (en) * 1957-10-08 Thiadiazine type natriuretic agents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2809194A (en) * 1957-10-08 Thiadiazine type natriuretic agents

Also Published As

Publication number Publication date
CH388972A (en) 1965-03-15

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