CH407135A - Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxydes - Google Patents
Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxydesInfo
- Publication number
- CH407135A CH407135A CH422462A CH422462A CH407135A CH 407135 A CH407135 A CH 407135A CH 422462 A CH422462 A CH 422462A CH 422462 A CH422462 A CH 422462A CH 407135 A CH407135 A CH 407135A
- Authority
- CH
- Switzerland
- Prior art keywords
- benzothiadiazine
- disulfamylaniline
- sulfamyl
- dioxide
- chloral
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 claims description 10
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 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 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000011698 potassium fluoride Substances 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- KRVABEGPNKGLOT-UHFFFAOYSA-N 4-amino-6-(trifluoromethyl)benzene-1,3-disulfonamide Chemical compound NC1=CC(C(F)(F)F)=C(S(N)(=O)=O)C=C1S(N)(=O)=O KRVABEGPNKGLOT-UHFFFAOYSA-N 0.000 claims description 2
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- RGUQWGXAYZNLMI-UHFFFAOYSA-N flumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O RGUQWGXAYZNLMI-UHFFFAOYSA-N 0.000 claims description 2
- QLGJNQICDRXXGG-UHFFFAOYSA-N (disulfamoylamino)benzene Chemical class NS(=O)(=O)N(S(N)(=O)=O)C1=CC=CC=C1 QLGJNQICDRXXGG-UHFFFAOYSA-N 0.000 claims 1
- -1 disulfamylaniline compound Chemical class 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical class CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- CGVXNZNOSZFBCD-UHFFFAOYSA-N 1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1=CNS(=O)(=O)C2=CC(S(=O)(=O)N)=CC=C21 CGVXNZNOSZFBCD-UHFFFAOYSA-N 0.000 description 1
- DLHWKJDYXPNWAI-UHFFFAOYSA-N 2,2,2-trichloro-1-ethoxyethanol Chemical compound CCOC(O)C(Cl)(Cl)Cl DLHWKJDYXPNWAI-UHFFFAOYSA-N 0.000 description 1
- QRKDOAWSBBGNLE-UHFFFAOYSA-N 2h-1,2,4-benzothiadiazine Chemical compound C1=CC=C2N=CNSC2=C1 QRKDOAWSBBGNLE-UHFFFAOYSA-N 0.000 description 1
- YRXAPDMJILMLSU-UHFFFAOYSA-N 4-amino-6-bromobenzene-1,3-disulfonamide Chemical compound NC1=CC(Br)=C(S(N)(=O)=O)C=C1S(N)(=O)=O YRXAPDMJILMLSU-UHFFFAOYSA-N 0.000 description 1
- GEZVQOGNDGUDNU-UHFFFAOYSA-N 4-amino-6-chloro-1-n-methylbenzene-1,3-disulfonamide Chemical compound CNS(=O)(=O)C1=CC(S(N)(=O)=O)=C(N)C=C1Cl GEZVQOGNDGUDNU-UHFFFAOYSA-N 0.000 description 1
- BIZYKPCIWRGRPJ-UHFFFAOYSA-N 4-amino-6-chloro-5-methylbenzene-1,3-disulfonamide Chemical compound CC1=C(N)C(S(N)(=O)=O)=CC(S(N)(=O)=O)=C1Cl BIZYKPCIWRGRPJ-UHFFFAOYSA-N 0.000 description 1
- OBRVGHAGEZLLGG-UHFFFAOYSA-N 4-amino-6-fluorobenzene-1,3-disulfonamide Chemical compound FC=1C(=CC(=C(N)C1)S(N)(=O)=O)S(N)(=O)=O OBRVGHAGEZLLGG-UHFFFAOYSA-N 0.000 description 1
- IJHBKNKFSJLONU-UHFFFAOYSA-N 4-amino-6-methoxybenzene-1,3-disulfonamide Chemical compound COC1=CC(N)=C(S(N)(=O)=O)C=C1S(N)(=O)=O IJHBKNKFSJLONU-UHFFFAOYSA-N 0.000 description 1
- JGFQDYAUPNZBMU-UHFFFAOYSA-N 4-amino-6-methylbenzene-1,3-disulfonamide Chemical compound CC1=CC(N)=C(S(N)(=O)=O)C=C1S(N)(=O)=O JGFQDYAUPNZBMU-UHFFFAOYSA-N 0.000 description 1
- IBNXNSNZXLVXSJ-UHFFFAOYSA-N 4-amino-6-nitrobenzene-1,3-disulfonamide Chemical compound NC1=CC([N+]([O-])=O)=C(S(N)(=O)=O)C=C1S(N)(=O)=O IBNXNSNZXLVXSJ-UHFFFAOYSA-N 0.000 description 1
- BOZSDDFQWJUBNG-UHFFFAOYSA-N 4-aminobenzene-1,3-disulfonamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1S(N)(=O)=O BOZSDDFQWJUBNG-UHFFFAOYSA-N 0.000 description 1
- BBNGVMNBBLPZIR-UHFFFAOYSA-N 4h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical class C1=CC=C2S(=O)(=O)N=CNC2=C1 BBNGVMNBBLPZIR-UHFFFAOYSA-N 0.000 description 1
- CAAKQRQFOMKFGK-UHFFFAOYSA-N 6-bromo-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(Br)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O CAAKQRQFOMKFGK-UHFFFAOYSA-N 0.000 description 1
- UNUUPKIWWPPKGU-UHFFFAOYSA-N 6-chloro-5-methyl-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1C=NS(=O)(=O)C2=C1C(C)=C(Cl)C(S(N)(=O)=O)=C2 UNUUPKIWWPPKGU-UHFFFAOYSA-N 0.000 description 1
- YYWLICGCICEVGT-UHFFFAOYSA-N 6-fluoro-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound C1=C(F)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O YYWLICGCICEVGT-UHFFFAOYSA-N 0.000 description 1
- OGXNOHZPFAKPAC-UHFFFAOYSA-N 6-methoxy-1,1-dioxo-4h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1C=NS(=O)(=O)C2=C1C=C(OC)C(S(N)(=O)=O)=C2 OGXNOHZPFAKPAC-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HAVZTGSQJIEKPI-UHFFFAOYSA-N benzothiadiazine Chemical group C1=CC=C2C=NNSC2=C1 HAVZTGSQJIEKPI-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 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
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)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Description
Verfahren zur Herstellung von 1,2,4-Benzothiadiazin-1,1-dioxyden Die vorliegende Erfindung betrifft ein neues Ver fahren zur Herstellung von 1,2,4-Benzothiadiazin- 1,1-dioxyden durch Reaktion zwischen Chloral und einer Disulfamylanilin-Verbindung, mit mindestens einer Sulfamylgruppe in der ortho-Stellung zu der Aminogruppe.
Als ein Merkmal der vorliegenden Erfindung ist überraschenderweise gefunden worden, dass falls Chloral mit einer Disulfamylanilin-Verbindung, vom oben beschriebenen Typus, in Gegenwart eines basi schen Katalysators, zur Reaktion gebracht wird, ein Ringschluss, unter Bildung des entsprechenden 1,2,4-Benzothiadiazin-1,1-dioxyds in hohen Ausbeu ten, erfolgt.
In Übereinstimmung mit der vorliegenden Erfin dung, wird die gewählte Disulfamylanilin-Verbindung mit Chloral, in Gegenwart einer Spur einer schwa chen Base, erhitzt.
Das im erfindungsgemässen Verfahren verwendete Chloral kann in jeder seiner aktiven Formen, wie Chloral selbst, oder Chloralhydrat oder Chloral- alkoholat, verwendet werden.
Die Reaktion wird vorteilhafterweise in Gegen wart eines Lösungsmittels für die Disulfamylanilin- Verbindung durchgeführt. Als für diesen Zweck ge eignete Lösungsmittel können Dimethylformamid oder Dimethylacetamide genannt werden.
Die oben erwähnten basischen Bedingungen wer den vorteilhafterweise, durch Zusetzen einer Spur jeder konventionellen schwachen Base, erhalten. Als für diesen Zweck insbesondere geeignet, wurden Kaliumfluorid, Natrium- oder Kaliumhydroxyd, ter tiäre Amine oder ähnliche, befunden.
An die Reaktion anschliessend kann das Reak tionsgemisch in jeder konventionellen Weise, zwecks Separierung der 1,2,4-Benzothiadia7in-1,1-dioxyd- Verbindung von dem Lösungsmittel, aufgearbeitet werden.
Das erfindungsgemässe Verfahren eignet sich ins besondere gut zur Herstellung von 1,2,4-Benzo- thiacliazinen, welche einen Sulfamylsubstituenten, ge bunden an den Benzolteil des Kernes enthalten, und welche noch zusätzlich mindestens einen andern Sub- stituenten, wie Halogen, einen halogenähnlichen Ra dikal oder ein Alkyl, Alkoxy, Nitro- oder einen ähnlichen,
an den Benzolteil des Kernes gebundenen Radikal, enthalten. Auch können Substituenten an einen der Stickstoffatome, in entweder der 2- oder 4-Stellung des Benzothiadiazinkernes der, gemäss dem erfindungsgemässen, neuen Verfahren hergestellten Produkte, gekettet sein.
Die gemäss dem vorliegenden Verfahren hergestellten 1,2,4-Benzothiadiazin-1,1- dioxyd-Verbindungen, welche einen Sulfamylsubsti- tuenten und mindestens einen andern, an den Benzol teil der Struktur gebundenen Substituenten enthal ten, sind, unter anderem, als diuretische und/oder saluretische Mittel nützlich.
Unter dieser Gruppe von Verbindungen besitzen Verbindungen der Struktur formel
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einen besonders hohen Wirksamkeitsgrad; in der ge nannten Strukturformel bedeutet R1 Halogen oder ein halogenähnliches Radikal, wie Chlor, Brom, Fluor, Trihalomethyl, wie Trifluoromethyl, Trichloro- methyl und ähnliche, ein Niederalkylradikal, vorteil- hafterweise mit 1-5 Kohlenstoffatomen, ein Nieder- alkoxyradikal,
vorteilhafterweise mit 1-5 Kohlen stoffatomen oder eine Nitrogruppe; R2 ist entweder in der 2- oder 4-Stellung am Stickstoffatom gebunden und ist Wasserstoff oder ein Niederalkylradikal, vor teilhafterweise mit 1-5 Kohlenstoffatomen;
und RB steht für Wasserstoff oder ein Niederalkylradikal, vor teilhafterweise mit 1-5 Kohlenstoffatomen. <I>Beispiel 1</I> Eine Lösung bestehend aus 1,4 g, 0,04 Mole, 5-Chlor-2,4-disulfamylanilin in 60 ml Dimethyl- formamid, 17,6 g, 0,12 Mole, Chloral und 4,6 g, 0;08 Mole wasserfreiem Kaliumfluorid wird auf einem Dampfbad während 3 Stunden erhitzt.
Danach setzt man 1-00 ml Wasser zu und fällt das halbfeste Pro dukt aus verdünntem Ammoniumhydroxyd wieder aus und erhält, in 76 % iger Ausbeute, 6-Chlor-7-sulf- amyl - 1,2,4 - Benzothiadiazin - 1,1 - dioxyd mit F=33'0 C.
<I>Beispiel 2</I> Nach Ersetzen des im Beispiel 1 verwendeten 5-Chlor-2,4-disulfamylanilins durch eine äquimolare Menge von 5-Trifluormethyl-2,4-disulfamylanilin und unter wesentlicher Befolgung der im Beispiel 1 be schriebenen Arbeitsweise, erhielt man 6-Trifluor- methyl-7-sulfamyl-1,2,4-Benzothiadiazin-1,1-dioxyd. <I>Beispiel 3</I> Eine Lösung von 0,04 Molen 5-Methyl-2,4-di- sulfamylanilin in 50 ml Dimethylacetamid, 0,02 Molen Chloralhydrat und eine Spur, ungefähr 0,08 Mole,
Trimethylamin werden auf einem Dampfbad während 5 Stunden erhitzt. Nach Zugabe von 100 ml Wasser wird 6-Methyl-7-sulfamyl-1,2,4-benzothia- diazin-1,1-dioxyd aus verdünntem Ammonium hydroxyd wieder ausgefällt.
<I>Beispiel 4</I> Eine Lösung von 5-Nitro-2,4-disulfamylanilin in 60 ml Dimethylformamid, 0,12 Mole Chloralalkoho- lat und eine Spur Natriumhydroxyd, ungefähr 0,08 Mole, werden auf dem Dampfbad während 31/2 Stunden erhitzt. Nach Zugabe von 100 ml Wasser wird die 6-Nitro-7-sulfamyl-1,2,4-benzothiadiazin- 1,1-dioxyd-Verbindung, aus verdünntem Ammonium hydroxyd, wieder ausgefällt.
<I>Beispiele 5-11</I> Nach Ersetzen des im Beispiel 1 verwendeten 5-Chlor-2,4-disulfamylanilin durch eine äquimoleku- lare Menge der folgenden Verbindung: Beispiel Nr. 5 5-Methoxy-2,4-disulfamylanilin, 6 5-Chlor-2-sulfamyl-4-(N-methylsulfamyl)- anilin, 7 5-Chlor-2-(N-methylsulfamyl)- 4-sulfamylaniän, 8 2,4-Disulfamylanilin, 9 5-Chlor-6-methyl-2,4-disulfamylanilin, 10 5-Fluor-2,4-disulfamylanilin, 11 5-Brom-2,
4-disulfamylanilin und unter wesentlicher Befolgung der im Beispiel 1 beschriebenen Arbeitsweise, erhält man: Beispiel Nr. 5 6-Methoxy-7-sulfamyl-1,2,4-benzothiadia- zin-1,1-dioxyd, 6 6-Chlor-7-(N-methylsulfamyl)-1,2,4-benzo- thiadiazin-1,1-dioxyd, 7 2-Methyl-6-chlor-7-sulfamyl-1,2,4-benzo- thiadiazin-1,1-dioxyd, 8 7-Sulfamyl-1,2,4-benzothiadiazin-1,1- dioxyd, 9 5-Methyl-6-chlor-7-sulfamyl-1,2,4-benzo- thiadiazin-1,1-dioxyd, 1,0 6-Fluor-7-sulfamyl-1,2,
4-benzothiadiazin 1,1-dioxyd, 11 6-Brom-7-sulfamyl-1,2,4-benzothiadiazin- 1,1-dioxyd.
Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxyden The present invention relates to a new process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxyden by reaction between chloral and a disulfamylaniline compound , with at least one sulfamyl group in the ortho position to the amino group.
As a feature of the present invention it has surprisingly been found that if chloral is reacted with a disulfamylaniline compound of the type described above in the presence of a basic catalyst, a ring closure, with formation of the corresponding 1,2,4- Benzothiadiazine 1,1-dioxyds in high Ausbeu takes place.
In accordance with the present invention, the selected disulfamylaniline compound is heated with chloral in the presence of a trace of a weak base.
The chloral used in the process according to the invention can be used in any of its active forms, such as chloral itself, or chloral hydrate or chloral alcoholate.
The reaction is advantageously carried out in the presence of a solvent for the disulfamylaniline compound. As solvents suitable for this purpose, dimethylformamide or dimethylacetamides can be mentioned.
The above-mentioned basic conditions are advantageously obtained by adding a trace of each conventional weak base. Potassium fluoride, sodium or potassium hydroxide, tertiary amines or the like have been found to be particularly suitable for this purpose.
Following the reaction, the reaction mixture can be worked up in any conventional manner for the purpose of separating the 1,2,4-benzothiadia7ine-1,1-dioxide compound from the solvent.
The process according to the invention is particularly suitable for the preparation of 1,2,4-benzothiacliazines which contain a sulfamyl substituent bonded to the benzene part of the core and which additionally contain at least one other substituent, such as halogen, a halogen-like one Radical or an alkyl, alkoxy, nitro or similar,
radical bound to the benzene part of the nucleus. Substituents can also be chained to one of the nitrogen atoms in either the 2- or 4-position of the benzothiadiazine nucleus of the products produced by the novel process according to the invention.
The 1,2,4-benzothiadiazine-1,1-dioxide compounds which are prepared according to the present process and which contain a sulfamyl substituent and at least one other substituent bound to the benzene part of the structure are, inter alia, diuretic and / or saluretic agents useful.
Among this group of compounds, compounds have the structure formula
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a particularly high degree of effectiveness; In the structural formula mentioned, R1 denotes halogen or a halogen-like radical, such as chlorine, bromine, fluorine, trihalomethyl, such as trifluoromethyl, trichloromethyl and the like, a lower alkyl radical, advantageously with 1-5 carbon atoms, a lower alkoxy radical,
advantageously with 1-5 carbon atoms or a nitro group; R2 is either bonded to the nitrogen atom in the 2- or 4-position and is hydrogen or a lower alkyl radical, advantageously with 1-5 carbon atoms;
and RB is hydrogen or a lower alkyl radical, advantageously with 1-5 carbon atoms. <I> Example 1 </I> A solution consisting of 1.4 g, 0.04 moles, 5-chloro-2,4-disulfamylaniline in 60 ml dimethylformamide, 17.6 g, 0.12 moles, chloral and 4.6 g, 0.08 moles of anhydrous potassium fluoride is heated on a steam bath for 3 hours.
Thereafter, 1-00 ml of water are added and the semi-solid product from dilute ammonium hydroxide is precipitated again and obtained in 76% yield, 6-chloro-7-sulfamyl-1,2,4-benzothiadiazine-1.1 - Dioxide with F = 33'0 C.
<I> Example 2 </I> After replacing the 5-chloro-2,4-disulfamylaniline used in Example 1 with an equimolar amount of 5-trifluoromethyl-2,4-disulfamylaniline and essentially following the procedure described in Example 1 , 6-trifluoromethyl-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide was obtained. <I> Example 3 </I> A solution of 0.04 moles of 5-methyl-2,4-disulfamylaniline in 50 ml of dimethylacetamide, 0.02 moles of chloral hydrate and a trace, approximately 0.08 moles,
Trimethylamine are heated on a steam bath for 5 hours. After adding 100 ml of water, 6-methyl-7-sulfamyl-1,2,4-benzothiazine-1,1-dioxide is reprecipitated from dilute ammonium hydroxide.
<I> Example 4 </I> A solution of 5-nitro-2,4-disulfamylaniline in 60 ml of dimethylformamide, 0.12 moles of chloral alcohol and a trace of sodium hydroxide, approximately 0.08 moles, are on the steam bath for 31 / Heated for 2 hours. After adding 100 ml of water, the 6-nitro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide compound is precipitated again from dilute ammonium hydroxide.
<I> Examples 5-11 </I> After replacing the 5-chloro-2,4-disulfamylaniline used in Example 1 with an equimolecular amount of the following compound: Example No. 5 5-Methoxy-2,4-disulfamylaniline , 6 5-chloro-2-sulfamyl-4- (N-methylsulfamyl) - aniline, 7 5-chloro-2- (N-methylsulfamyl) - 4-sulfamylane, 8 2,4-disulfamylaniline, 9 5-chloro-6 -methyl-2,4-disulfamylaniline, 10 5-fluoro-2,4-disulfamylaniline, 11 5-bromo-2,
4-disulfamylaniline and by strictly following the procedure described in Example 1, one obtains: Example No. 5 6-methoxy-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide, 6 6-chloro 7- (N-methylsulfamyl) -1,2,4-benzothiadiazine-1,1-dioxide, 7 2-methyl-6-chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1 -dioxide, 8 7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide, 9 5-methyl-6-chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide , 1.0 6-fluoro-7-sulfamyl-1,2,
4-benzothiadiazine 1,1-dioxide, 11 6-bromo-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10133261A | 1961-04-07 | 1961-04-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH407135A true CH407135A (en) | 1966-02-15 |
Family
ID=22284090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH422462A CH407135A (en) | 1961-04-07 | 1962-04-06 | Process for the preparation of 1,2,4-benzothiadiazine-1,1-dioxydes |
Country Status (4)
| Country | Link |
|---|---|
| CH (1) | CH407135A (en) |
| DK (1) | DK106332C (en) |
| FI (1) | FI43599B (en) |
| SE (1) | SE302612B (en) |
-
1962
- 1962-03-30 FI FI0689/62A patent/FI43599B/fi active
- 1962-04-05 DK DK157662AA patent/DK106332C/en active
- 1962-04-06 SE SE3855/62A patent/SE302612B/xx unknown
- 1962-04-06 CH CH422462A patent/CH407135A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK106332C (en) | 1967-01-23 |
| FI43599B (en) | 1971-02-01 |
| SE302612B (en) | 1968-07-29 |
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