DE1163332B - Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazine-1, 1-dioxide - Google Patents
Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazine-1, 1-dioxideInfo
- Publication number
- DE1163332B DE1163332B DEK39343A DEK0039343A DE1163332B DE 1163332 B DE1163332 B DE 1163332B DE K39343 A DEK39343 A DE K39343A DE K0039343 A DEK0039343 A DE K0039343A DE 1163332 B DE1163332 B DE 1163332B
- Authority
- DE
- Germany
- Prior art keywords
- chloro
- sulfamyl
- dihydro
- dioxide
- benzothiadiazine
- 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
Links
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 33
- IHJCXVZDYSXXFT-UHFFFAOYSA-N chloraminophenamide Chemical compound NC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O IHJCXVZDYSXXFT-UHFFFAOYSA-N 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 229930040373 Paraformaldehyde Natural products 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 229920002866 paraformaldehyde Polymers 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 1
- -1 ammonium ions Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
Verfahren zur Herstellung von 6-Chlor-7-sulfamyl-3 ,4-dihydro- 1, 2,4-benzothiadiazinl,l-dioxyd Es ist bereits bekannt, 6-Chlor-7-sulfamyl-3,4-dihydro- 1 2,4-benzothiadiazin- 1,1 -dioxyd durch Umsetzung von 5-Chlor-2,4-disulfamylanilin mit Formaldehyd in Gegenwart eines sauren Katalysators herzustellen (vgl. Experientia, 14, [1958], S. 463 und 464).Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazinl, l-dioxide It is already known that 6-chloro-7-sulfamyl-3,4-dihydro- 1 2,4-benzothiadiazine-1,1-dioxide by reacting 5-chloro-2,4-disulfamylaniline with formaldehyde in the presence of an acidic catalyst (see Experientia, 14, [1958], pp. 463 and 464).
Nach der schweizerischen Patentschrift 337203 kann der Formaldehyd auch in Form seiner Polymeren, z. B. According to Swiss patent 337203, formaldehyde can also in the form of its polymers, e.g. B.
Paraformaldehyd, eingesetzt werden; nach den bekanntgemachten Unterlagen des belgischen Patentes 578374 wird die Umsetzung mit Formaldehyd in Gegenwart eines alkalisch reagierenden Katalysators durchgeführt.Paraformaldehyde, can be used; according to the published documents of Belgian patent 578374 is the reaction with formaldehyde in the presence of a alkaline reacting catalyst carried out.
Bei diesen bekannten Verfahren wird 1 Mol 5-Chlor-2,4-disulfamylanilin mit 1 Mol Formaldehyd oder Paraformaldehyd umgesetzt, da ein Überschuß von Formaldehyd die Ausbeute durch Bildung von Sekundärprodukten vermindert. In these known processes, 1 mole of 5-chloro-2,4-disulfamylaniline is used reacted with 1 mole of formaldehyde or paraformaldehyde, as there is an excess of formaldehyde the yield is reduced by the formation of secondary products.
Es wurde nun gefunden, daß man 6-Chlor-7-sulfamyl - 3,4 - dihydro -1,2,4 - benzothiadiazin - 1,1 - dioxyd durch Umsetzung von 5-Chlor-2,4-disulfamylanilin mit Formaldehyd oder Paraformaldehyd in Gegenwart eines alkalisch reagierenden Katalysators und eines Lösungsmittels bei erhöhter Temperatur erhält, wenn man als Katalysator Ammoniak und als Lösungsmittel Wasser verwendet. It has now been found that 6-chloro-7-sulfamyl - 3,4 - dihydro -1,2,4 - benzothiadiazine - 1,1 - dioxide by reacting 5-chloro-2,4-disulfamylaniline with formaldehyde or paraformaldehyde in the presence of an alkaline catalyst and a solvent at elevated temperature when used as a catalyst Ammonia and water as solvent used.
Das 6-Chlor-7-sulfamyl-3,4-dihydro- 1 ,2,4-benzothiadiazin- 1,1 -dioxyd, welches als Diureticum eine große Bedeutung erlangt hat, wird dabei in Ausbeuten von über 90 0/o erhalten. 6-chloro-7-sulfamyl-3,4-dihydro-1, 2,4-benzothiadiazine-1,1-dioxide, which has gained great importance as a diuretic, is used in yields received by over 90 0 / o.
Das erfindungsgemäße Verfahren ist überraschend denn es war nicht vorauszusehen, daß die Gegenwart von Ammoniumionen die Reaktion von 5-Chlor-2,4-disulfamylanilin mit Formaldehyd so günstig beeinflußt, daß auch bei einem Überschuß von Formaldehyd nur ein einziges Reaktionsprodukt, nämlich das 6-Chlor-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazinl,l-dioxyd, gebildet wird. The inventive method is surprising because it was not anticipate that the presence of ammonium ions will trigger the reaction of 5-chloro-2,4-disulfamylaniline influenced so favorably with formaldehyde that even with an excess of formaldehyde only a single reaction product, namely 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazinl, l-dioxide, is formed.
Gegenüber dem aus den bekanntgemachten Unterlagen des belgischen Patentes 578 374 bekannten Verfahren zur Herstellung von 6-Chlor-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyd ist das erfindungsgemäße Verfahren auf Grund seiner höheren Ausbeuten technisch fortschrittlich. Compared to that from the published documents of the Belgian Patent 578,374 known process for the preparation of 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide the process according to the invention is technical due to its higher yields progressive.
Das Ammoniak wird in katalytischen Mengen zugesetzt, zweckmäßig dergestalt, daß ein schwacher Ammoniakgeruch bestehenbleibt. The ammonia is added in catalytic amounts, expediently in such a way that that a faint ammonia odor remains.
Der Formaldehyd oder Paraformaldehyd wird dem 5-Chlor-2,4-disulfamylanilin im Molverhältnis 1:1 oder im Überschuß zugesetzt. The formaldehyde or paraformaldehyde is the 5-chloro-2,4-disulfamylaniline added in a molar ratio of 1: 1 or in excess.
Beispiel 1 5,7 g 5-Chlor-2,4-disulfamylanilin werden in 200 bis 250 ml Wasser suspendiert. Man gibt dann2 bis 4 ml kon- zentrierte Ammoniaklösung und anschließend 2 bis 3,2 ml Formaldehydlösung (360/,in) hinzu und kocht 1 Stunde unter Rückfluß. Example 1 5.7 g of 5-chloro-2,4-disulfamylaniline are in 200 to 250 ml of water suspended. Then add 2 to 4 ml of centered ammonia solution and then add 2 to 3.2 ml of formaldehyde solution (360 /, in) and boil for 1 hour Reflux.
Nach dem Erkalten kristallisiert das 6-Chlor-7-sulfamyl-3,4-dihydro- 1,2,4-benzothiadiazin- 1,1 -dioxyd in glitzernden Kristallen aus. Man läßt einige Stunden in der Kälte stehen und saugt die Kristalle ab. Schmp. 270 bis 272"C; Ausbeute 5,2 g. After cooling, the 6-chloro-7-sulfamyl-3,4-dihydro- 1,2,4-benzothiadiazine-1,1-dioxide in glittering crystals. Some are left Stand in the cold for hours and suck off the crystals. M.p. 270 to 272 "C; yield 5.2 g.
Durch Eindampfen der Mutterlauge lassen sich 0,5 bis 0,6 g farblose Kristalle erhalten, so daß die Gesamtausbeute 5,7 bis 5,8 g (= 96 bis 970/o) beträgt. Evaporation of the mother liquor leaves 0.5 to 0.6 g colorless Crystals are obtained so that the total yield is 5.7 to 5.8 g (= 96 to 970 / o).
Beispiel 2 Zu 28,3 g 5-Chlor-2,4-disulfamylanilin, in 600 ml Wasser suspendiert, werden 25 ml konzentrierte Ammoniaklösung und 80 ml Formalin (360/,in) zugesetzt, und das Ganze wird zum Sieden erhitzt. Es löst sich innerhalb weniger Minuten alles auf. Nach weiteren 10 Minuten Kochen fallen kleine harte Nadeln aus, die sich beim Kochen vermehren und nach Zugabe von 3 bis 5 ml konzentrierter Ammoniaklösung auflösen. Example 2 To 28.3 g of 5-chloro-2,4-disulfamylaniline, in 600 ml of water suspended, 25 ml of concentrated ammonia solution and 80 ml of formalin (360 /, in) added, and the whole is heated to the boil. It dissolves within a few Minutes everything up. After another 10 minutes of cooking, small hard needles fall out, which multiply when boiled and after adding 3 to 5 ml of concentrated ammonia solution dissolve.
Nach kurzer Zeit fällt wieder ein Niederschlag aus.After a short time, a precipitate separates out again.
Man läßt erkalten und saugt die Kristalle ab. Schmp.220 bis 222"C; Ausbeute 34 g. Die Mutterlauge wird auf die Hälfte eingedampft, wobei noch 6 bis 8 g auskristallisieren. Man kocht die vereinigte Kristallmasse mit 2,5 bis 3 1 Wasser. Es löst sich alles, und nach dem Erkalten fällt das 6-Chlor-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyd als schillernde, farblose Blättchen aus. Schmp. 269 bis 271"C; Ausbeute 25 g. Nach längerem Stehen der Mutterlauge können noch 3 bis 4 g gewonnen werden, so daß die Gesamtausbeute 28 bis 29 g (= 95 bis 970/o) beträgt.It is allowed to cool and the crystals are filtered off with suction. M.p. 220 to 222 "C; Yield 34g. The mother liquor is evaporated to half, with 6 to 8 g crystallize out. The combined crystal mass is boiled with 2.5 to 3 liters of water. Everything dissolves, and after cooling, the 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide falls as iridescent, colorless leaves. Mp. 269 to 271 "C; Yield 25 g prolonged standing of the mother liquor can still be obtained 3 to 4 g, so that the The total yield is 28 to 29 g (= 95 to 970 / o).
Beispiel 3 5,7 g 5-Chlor-2,4-disulfamylanilin werden in 150 ml Wasser suspendiert. Man gibt hierzu 2 bis 3 ml konzentrierte Ammoniaklösung und 0,6 g Paraformaldehyd. Nun kocht man 1 Stunde zum Sieden. Nach Filtrieren und Erkalten erhält man schillernde Blättchen. Example 3 5.7 g of 5-chloro-2,4-disulfamylaniline are dissolved in 150 ml of water suspended. 2 to 3 ml of concentrated are added to this Ammonia solution and 0.6 g paraformaldehyde. Now boil to the boil for 1 hour. After filtering and When cooling down, you get shimmering leaves.
Schmp. 270 bis 272"C; Ausbeute 5,5 g (= 92°/o).Mp. 270 to 272 "C; Yield 5.5 g (= 92%).
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK39343A DE1163332B (en) | 1959-12-04 | 1959-12-04 | Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazine-1, 1-dioxide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK39343A DE1163332B (en) | 1959-12-04 | 1959-12-04 | Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazine-1, 1-dioxide |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1163332B true DE1163332B (en) | 1964-02-20 |
Family
ID=7221683
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK39343A Pending DE1163332B (en) | 1959-12-04 | 1959-12-04 | Process for the preparation of 6-chloro-7-sulfamyl-3, 4-dihydro-1, 2,4-benzothiadiazine-1, 1-dioxide |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1163332B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7544711B2 (en) | 1996-09-04 | 2009-06-09 | Nicox S.A. | Use of nitroderivatives in urinary incontinence |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE578374A (en) * | 1959-02-13 | 1959-08-31 | Simes | Process for preparing 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadaizine-1,1-dioxide. |
-
1959
- 1959-12-04 DE DEK39343A patent/DE1163332B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE578374A (en) * | 1959-02-13 | 1959-08-31 | Simes | Process for preparing 6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadaizine-1,1-dioxide. |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7544711B2 (en) | 1996-09-04 | 2009-06-09 | Nicox S.A. | Use of nitroderivatives in urinary incontinence |
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