CH387642A - Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes - Google Patents

Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes

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Publication number
CH387642A
CH387642A CH18463A CH1846359A CH387642A CH 387642 A CH387642 A CH 387642A CH 18463 A CH18463 A CH 18463A CH 1846359 A CH1846359 A CH 1846359A CH 387642 A CH387642 A CH 387642A
Authority
CH
Switzerland
Prior art keywords
benzothiadiazine
dihydro
sep
sulfamyl
starting materials
Prior art date
Application number
CH18463A
Other languages
German (de)
Inventor
Destevens George
Harvey Werner Lincoln
Original Assignee
Ciba Geigy
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 Ciba Geigy filed Critical Ciba Geigy
Publication of CH387642A publication Critical patent/CH387642A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • 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
    • C07D285/30—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 hydrocarbon radicals, substituted by hetero atoms, attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Description

  

  Verfahren zur     Herstellung    von     Sulfainyl-3,4-dihydro-1,2,4-benzothiadiazin-1,1-dioxyden       Gegenstand der vorliegenden Erfindung ist ein  Verfahren zur Herstellung von     3,4-Dihydro-1,2,4-          benzothiadiazin-1,1-dioxyden    der Formel  
EMI0001.0005     
    worin R einen     Halogenalkylrest,    besonders mit 1-5       Kohlenstoffatomen,    bedeutet. Als     Halogenalkylreste     seien in erster Linie genannt, z. B.     Chlormethyl-,          Dichlormethyl-    oder     Brommethylreste.     



  Die neuen     3,4-Dihydro-        1,2,4-benzothiadiazin-          1,1-dioxyde    und deren     Salze,    insbesondere mit       Alkalimetallen,    zeigen eine     diuretische    und     natriure-          tische    Wirksamkeit und sollen als     Heilmittel    Ver  wendung finden. Unter diesen Verbindungen ist noch  besonders das     3-Chlormethyl-6-chlor-7-sulfamyl-3,4-          dihydro-1,2,4-benzothiadiazin-1,1-dioxyd    wie auch  seine     Alkalimetallsalze    durch eine besonders hohe  Wirksamkeit ausgezeichnet.

      Die genannten Verbindungen     können    als Heil  mittel     in    Form von pharmazeutischen Präparaten  verwendet werden, welche diese Verbindungen zu  sammen mit den pharmazeutischen organischen  oder anorganischen, festen oder     flüssigen    Träger  substanzen, die für     enterale,    z. B. orale, oder     par-          enterale    Gabe geeignet sind, enthalten. Für die Bil  dung derselben kommen solche Stoffe in Frage, die  mit den neuen Verbindungen nicht reagieren, wie  z. B.

   Wasser, Gelatine, Milchzucker, Stärke,     Magne-          siumstearat,    Talk, pflanzliche Öle,     Benzylalkohole,     Gummi,     Polyalkylenglykole,        Vaseline,    Cholesterin  oder andere bekannte     Arzneimittelträger.    Die  pharmazeutischen Präparate     können    z.

   B. als Ta  bletten, Dragees, Kapseln oder in flüssiger Form als  Lösungen, Suspensionen oder Emulsionen     vorliegen.     Gegebenenfalls sind sie sterilisiert und bzw. oder  enthalten     Hilfsstoffe,    wie     Konservierungs-,        Stabili-          sierungs-,    Netz- oder     Emulgiermittel,        Salze    zur Ver  änderung des     osmotischen    Druckes oder Puffer. Sie  können auch noch andere therapeutisch wertvolle  Stoffe, z.

   B.     hypotensive    Mittel, enthalten, wie       Rauwolfia-    oder     Veratrum-Alkaloide,    beispielsweise       Reserpin,        Rescinnamin,        Deserpidin,        Germin    oder       Protoveratrin,    synthetische     hypotensive    Mittel, z. B.

         Hydralazin,    oder     Ganglienblocker,    wie     Chlorisond-          amin.       Die neuen Verbindungen werden erhalten, wenn man in     Benzothiadiazin-1,1-dioxyden    der Formel  
EMI0001.0059     
      die     C=N-Doppelbindung    reduziert. Vorzugsweise  führt man diese Reduktion mit     Alkalimetallbor-          hydriden,    wie     Lithium-,    Kalium- oder besonders     Na-          triumborhydrid,    durch.

   Diese Metallhydride verwen  det man in Gegenwart eines Lösungsmittels, wie       wässrigen    Lösungen von     Alkahmetallhydroxyden,     z. B.     Lithium-,    Natrium- oder     Kaliumhydroxyden,     eines Äthers, wie     Diäthylenglykoldimethyläther,    oder  eines     flüssigen        Carbonsäureamids,    wie eines     Form-          amids,    z.

   B.     Formamid    selbst oder     Dirnethylform-          amid.    Die Reduktion lässt sich bei Raumtempera  tur oder bei erhöhter Temperatur, wenn erwünscht,  in     Gegenwart    eines     inerten    Gases, wie Stickstoff,  durchführen. Die     C=N-Doppelbindung    kann aber  auch elektrolytisch nach an sich bekannten Ver  fahrensmethoden     reduziert    werden.  



  Die zu diesen Verfahrensmethoden verwendeten  Ausgangsmaterialien sind bekannt oder lassen sich  auf an sich bekannte Weise erhalten.  



  Je nach den Reaktionsbedingungen erhält man  die neuen Verbindungen in freier Form oder in  Form ihrer     Salze.    Erhaltene     Metallsalze    können z. B.  durch Reaktion mit     wässrigen    sauren Mitteln, wie  Mineralsäure, z. B.     Halogenwasserstoffsäure,    bei  spielsweise     Salzsäure    oder Schwefelsäure, in die  freien Verbindungen übergeführt werden. Diese wie  derum lassen sich in die     Metallsalze,    wie Alkali  metallsalze, überführen durch Behandeln z. B. mit  einem     Metallhydroxyd,    wie Natrium- oder Kalium  hydroxyd, in einem Lösungsmittel, wie einem     Alka-          nol,    z. B.

   Methanol oder     Athanol,    oder     in    Wasser  und anschliessendes Abdampfen des Lösungsmittels,  oder durch     Reagierenlassen    der freien Verbindung  in einem Äther, wie     p-Dioxan    oder     Diäthylenglykol-          dimethylätherlösung,    mit einem     Alkalimetallhydrid     oder     -amid,    z. B. Natrium- oder     Kaliumhydrid    oder       -amid.    Dabei lassen sich Mono- oder     Polysalze    er  halten.  



  Die Erfindung betrifft auch Ausführungsformen  des Verfahrens, bei denen ein Ausgangsstoff in Form  eines unter den Reaktionsbedingungen gebildeten  Reaktionsgemisches verwendet wird.  



  Die Temperaturen sind in dem nachfolgenden  Beispiel in Celsiusgraden angegeben.  



  <I>Beispiel</I>  Zu 75     cm3    im Eisbad gekühltem     Diäthylen-          glykol-dimethyläther    gibt man 0,3 g fein pulveri  siertes wasserfreies     Aluminumchlorid,    lässt die Mi  schung auf Raumtemperatur erwärmen und fügt  0,8 g 3 -     Dichlormethyl    - 6- chlor- 7 -     sulfamyl-1,2,4-          benzothiadiazin-1,1-dioxyd    und dann eine Lösung  von 0,4 g     Natriumborhydrid    in 20     cm3        Diäthylen-          glykol-dimethyläther    zu.

   Man     rührt    die Reaktions  mischung 30 Minuten bei Raumtemperatur und 1  Stunde bei 85  und kühlt im Eisbad, gibt 15     cm3     Wasser zur Reaktionsmischung, säuert sie mit 2n  wässriger     Salzsäure    an und dampft unter verminder-         tem    Druck zur Trockne ein. Der Rückstand wird  durch Behandeln mit Wasser bei Raumtemperatur  kristallisiert und einer     Dünnschichtchromatographie     unterworfen.  



  Eine Lösung von 0,6 g des kristallinen Rück  standes in Methanol, dem wenig     N,N-Dimethylform-          amid    zugefügt wurde, gibt man auf eine mit Alumi  niumoxyd beschichtete Glasplatte und entwickelt das       Chromatogramm    mit einer     1:1-Mischung    von  Benzol und     N,N-Dimethylformamid.    Als Bestim  mungshilfsmittel verwendet man einen     mit    Anis  aldehyd und Formaldehyd imprägnierten Streifen.

    Die     einzelnen    Bänder wurden abgeschnitten und       eluiert    und die so erhaltenen Produkte zur Bestim  mung ihrer Reinheit und der     Rf-Werte    im gleichen       Lösungsmittelgemisch    nochmals     chromatographiert.     
EMI0002.0070     
  
    Band <SEP> erhaltene <SEP> Menge <SEP> Rf-Wert
<tb>  1 <SEP> 0,145 <SEP> g <SEP> 0,08
<tb>  2 <SEP> 0,359 <SEP> g <SEP> 0,08
<tb>  3 <SEP> 0,025 <SEP> g <SEP> 0,37
<tb>  4 <SEP> 0,014 <SEP> g <SEP> 0,95
<tb>  5 <SEP> 0,012 <SEP> g       Das aus dem Band Nr.

   3 mit dem     Rf-Wert    0,37  isolierte Produkt ist das     3-Dichlormethyl-6-chlor-7-          sulfamyl-    3,4 -     dihydro-1,2,4    -     benzothiadiazin-1,1-di-          oxyd.    Es schmilzt bei 261-262 .  



  Das verwendete Ausgangsmaterial lässt sich wie  folgt erhalten:  Man erhitzt eine Mischung von 14,5 g     5-Chlor-          2,4-disulfamyl-anilin    und 7,5 g     Dichloressigsäure-          chlorid    in 60     cm3        Diäthylenglykol-dimethyläther    2  Stunden auf 100 , dampft die Reaktionsmischung  unter vermindertem Druck zur Trockne ein und  kristallisiert den Rückstand mit Wasser. Das so er  haltene     5-Chlor-N-dichloracetyl-2,4-disulfamylanilin          schmilzt    nach dem     Umkristallisieren    aus Methanol  bei 234-238 .  



  Man kocht 1 g     5-Chlor-N-dichloracetyl-2,4-di-          sulfamyl-anilin    in 25     cm3    Wasser 2 Stunden am       Rückflusskühler,    kühlt auf Raumtemperatur ab, wo  bei das     3-Dichlormethyl-6-chlor-7-sulfamyl-1,2,4-          benzothiadiazin-1,1-dioxyd    ausfällt. Nach dem Ab  filtrieren und Trocknen schmilzt es bei ungefähr 310 .  



  In analoger Weise, ausgehend von den entspre  chenden Ausgangsstoffen, gelangt man zum       3-Brommethyl-6-chlor-7-sulfamyl-3,4-dihydro-          1,2,4-benzothiadiazin-1,1-dioxyd,     F.215-216  und       3-Dichlormethyl-6-chlor-7-sulfamyl-3,4-dihydro-          1,2,4-benzothiadiazin-1,1-dioxyd,     F. 242-244 .



  Process for the preparation of sulfainyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes The present invention relates to a process for the preparation of 3,4-dihydro-1,2,4-benzothiadiazine-1 , 1-dioxydes of the formula
EMI0001.0005
    wherein R is a haloalkyl radical, especially with 1-5 carbon atoms. As haloalkyl radicals are primarily mentioned, for. B. chloromethyl, dichloromethyl or bromomethyl radicals.



  The new 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides and their salts, in particular with alkali metals, show a diuretic and natriuretic effectiveness and are intended to be used as remedies. Among these compounds, 3-chloromethyl-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide and its alkali metal salts are particularly distinguished by their particularly high effectiveness.

      The compounds mentioned can be used as medicinal agents in the form of pharmaceutical preparations, which substances these compounds together with the pharmaceutical organic or inorganic, solid or liquid carrier that are used for enteral, z. B. oral or parenteral administration are suitable. For the formation of the same substances come into question that do not react with the new compounds, such. B.

   Water, gelatine, milk sugar, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, gum, polyalkylene glycols, petrolatum, cholesterol or other known excipients. The pharmaceutical preparations can e.g.

   B. as Ta tablets, coated tablets, capsules or in liquid form as solutions, suspensions or emulsions. If necessary, they are sterilized and / or contain auxiliaries, such as preservatives, stabilizers, wetting agents or emulsifiers, salts to change the osmotic pressure or buffers. You can also use other therapeutically valuable substances, e.g.

   B. hypotensive agents, such as Rauwolfia or Veratrum alkaloids such as reserpine, rescinnamine, deserpidine, germin or protoveratrine, synthetic hypotensive agents, e.g. B.

         Hydralazine, or ganglion blockers, such as chloroisondamine. The new compounds are obtained when one in benzothiadiazine-1,1-dioxyden of the formula
EMI0001.0059
      the C = N double bond is reduced. This reduction is preferably carried out with alkali metal borohydrides, such as lithium, potassium or, in particular, sodium borohydride.

   These metal hydrides are used in the presence of a solvent, such as aqueous solutions of alkali metal hydroxides, e.g. B. lithium, sodium or potassium hydroxides, an ether such as diethylene glycol dimethyl ether, or a liquid carboxamide, such as a formamide, z.

   B. formamide itself or dirnethylformamide. The reduction can be carried out at room temperature or at an elevated temperature, if desired, in the presence of an inert gas such as nitrogen. The C = N double bond can, however, also be reduced electrolytically using methods known per se.



  The starting materials used for these process methods are known or can be obtained in a manner known per se.



  Depending on the reaction conditions, the new compounds are obtained in free form or in the form of their salts. Metal salts obtained can e.g. B. by reaction with aqueous acidic agents such as mineral acid, e.g. B. hydrohalic acid, for example hydrochloric acid or sulfuric acid, are converted into the free compounds. These like in turn can be converted into the metal salts, such as alkali metal salts, by treating z. B. with a metal hydroxide, such as sodium or potassium hydroxide, in a solvent such as an alkanol, z. B.

   Methanol or ethanol, or in water and subsequent evaporation of the solvent, or by reacting the free compound in an ether, such as p-dioxane or diethylene glycol dimethyl ether solution, with an alkali metal hydride or amide, e.g. B. sodium or potassium hydride or amide. Mono- or poly-salts can be obtained.



  The invention also relates to embodiments of the process in which a starting material is used in the form of a reaction mixture formed under the reaction conditions.



  In the example below, the temperatures are given in degrees Celsius.



  <I> Example </I> 0.3 g of finely powdered anhydrous aluminum chloride is added to 75 cm3 of diethylene glycol dimethyl ether cooled in an ice bath, the mixture is allowed to warm to room temperature and 0.8 g of 3 - dichloromethyl - 6- chlorine-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide and then a solution of 0.4 g sodium borohydride in 20 cm3 diethylene glycol dimethyl ether.

   The reaction mixture is stirred for 30 minutes at room temperature and 1 hour at 85 and cooled in an ice bath, 15 cm3 of water are added to the reaction mixture, it is acidified with 2N aqueous hydrochloric acid and evaporated to dryness under reduced pressure. The residue is crystallized by treatment with water at room temperature and subjected to thin layer chromatography.



  A solution of 0.6 g of the crystalline residue in methanol, to which a little N, N-dimethylformamide was added, is placed on a glass plate coated with aluminum oxide and the chromatogram is developed with a 1: 1 mixture of benzene and N , N-dimethylformamide. A strip impregnated with anise aldehyde and formaldehyde is used as a determination aid.

    The individual bands were cut off and eluted, and the products thus obtained were chromatographed again in the same solvent mixture to determine their purity and the Rf values.
EMI0002.0070
  
    Band <SEP> received <SEP> amount <SEP> Rf value
<tb> 1 <SEP> 0.145 <SEP> g <SEP> 0.08
<tb> 2 <SEP> 0.359 <SEP> g <SEP> 0.08
<tb> 3 <SEP> 0.025 <SEP> g <SEP> 0.37
<tb> 4 <SEP> 0.014 <SEP> g <SEP> 0.95
<tb> 5 <SEP> 0.012 <SEP> g That from volume no.

   3 product isolated with an Rf value of 0.37 is 3-dichloromethyl-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide. It melts at 261-262.



  The starting material used can be obtained as follows: A mixture of 14.5 g of 5-chloro-2,4-disulfamyl-aniline and 7.5 g of dichloroacetic acid chloride in 60 cm3 of diethylene glycol dimethyl ether is heated to 100 for 2 hours, the Reaction mixture to dryness under reduced pressure and the residue crystallizes with water. The 5-chloro-N-dichloroacetyl-2,4-disulfamylaniline thus obtained melts after recrystallization from methanol at 234-238.



  1 g of 5-chloro-N-dichloroacetyl-2,4-disulfamyl-aniline is boiled in 25 cm3 of water for 2 hours on a reflux condenser, cooled to room temperature, where the 3-dichloromethyl-6-chloro-7-sulfamyl- 1,2,4-benzothiadiazine-1,1-dioxide precipitates. After filtering and drying, it melts at around 310.



  In an analogous manner, starting from the corresponding starting materials, one arrives at 3-bromomethyl-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide, F.215- 216 and 3-dichloromethyl-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxide, m.p. 242-244.

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung von 3,4-Dihydro- 1,2,4-benzothiadiazin-l,l-dioxyden der Formel EMI0003.0001 worin R einen Halogenalkylrest bedeutet, dadurch gekennzeichnet, dass man in Benzothiadiazin-1,1- dioxyden der Formel EMI0003.0007 die C=N-Doppelbindung reduziert UNTERANSPRÜCHE 1. Verfahren nach Patentanspruch, dadurch ge kennzeichnet, dass man die Reduktion mit Alkali- metallborhydriden durchführt. 2. PATENT CLAIM Process for the preparation of 3,4-dihydro-1,2,4-benzothiadiazine-l, l-dioxyden of the formula EMI0003.0001 wherein R denotes a haloalkyl radical, characterized in that in benzothiadiazine-1,1-dioxydes of the formula EMI0003.0007 the C = N double bond is reduced. SUBClaims 1. The method according to claim, characterized in that the reduction is carried out with alkali metal borohydrides. 2. Verfahren nach Patentanspruch, dadurch ge kennzeichnet, dass man die Reduktion elektrolytisch durchführt. 3. Verfahren nach Patentanspruch und den Un teransprüchen 1 und 2, dadurch gekennzeichnet, dass man Ausgangsstoffe verwendet, worin R einen Halogenalkylrest mit 1-5 Kohlenstoffatomen be deutet. 4. Verfahren nach Patentanspruch und den Un- ansprüchen 1 und 2, dadurch gekennzeichnet, dass man Ausgangsstoffe verwendet, worin R den Chlor- methylrest bedeutet. 5. Process according to claim, characterized in that the reduction is carried out electrolytically. 3. The method according to claim and the un terclaims 1 and 2, characterized in that starting materials are used in which R is a haloalkyl radical having 1-5 carbon atoms. 4. The method according to claim and un- claims 1 and 2, characterized in that starting materials are used in which R is the chloromethyl radical. 5. Verfahren nach Patentanspruch und den Un teransprüchen 1 und 2, dadurch gekennzeichnet, dass man Ausgangsstoffe verwendet, worin R den Di- chlormethylrest bedeutet. 6. Verfahren nach Patentanspruch und den Un teransprüchen 1 und 2, dadurch gekennzeichnet, dass man Ausgangsstoffe verwendet, worin R den Brom methylrest bedeutet. Process according to patent claim and the sub-claims 1 and 2, characterized in that starting materials are used in which R denotes the dichloromethyl radical. 6. The method according to claim and the un terclaims 1 and 2, characterized in that starting materials are used in which R is the bromine methyl radical.
CH18463A 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes CH387642A (en)

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
US71845258A 1958-03-03 1958-03-03
US72724258A 1958-04-09 1958-04-09
US74058258A 1958-06-09 1958-06-09
US75162058A 1958-07-29 1958-07-29
US76448258A 1958-09-29 1958-09-29
DEC0024176 1959-02-27
DEC0028408 1959-02-27
DEC0028409 1959-02-27
DEC0024177 1959-02-27
DEC0024178 1959-02-27

Publications (1)

Publication Number Publication Date
CH387642A true CH387642A (en) 1965-02-15

Family

ID=27579177

Family Applications (4)

Application Number Title Priority Date Filing Date
CH6978359A CH371454A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes
CH18063A CH376514A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes
CH18163A CH377365A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes
CH18463A CH387642A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes

Family Applications Before (3)

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CH6978359A CH371454A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes
CH18063A CH376514A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes
CH18163A CH377365A (en) 1958-03-03 1959-02-19 Process for the preparation of sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxydes

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CH (4) CH371454A (en)
DE (4) DE1445005A1 (en)
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Also Published As

Publication number Publication date
OA03826A (en) 1971-12-24
DE1445008A1 (en) 1968-10-24
DE1445574A1 (en) 1969-01-16
DE1445006B2 (en) 1975-05-07
DE1445005A1 (en) 1968-10-24
MY6200051A (en) 1962-12-31
DE1445006A1 (en) 1968-10-24
DE1112079B (en) 1961-08-03
FR1264468A (en) 1961-06-23
OA01178A (en) 1969-01-25
DE1445007A1 (en) 1968-10-24
CH376514A (en) 1964-04-15
GB861367A (en) 1961-02-22
FR1217929A (en) 1960-05-06
CH371454A (en) 1963-08-31
CH377365A (en) 1964-05-15

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