Acidity 1.2.4- benzothiadiazine 1,1-dioxides

B) A solution of BB g of 5-chloro-2,4-disulfamylaniline in 1.1 liters of BB% formic acid was heated under reflux for 2 hours. After removal of 200 ml of solvent by distillation, one liter of water was added and the product collected, washed with water and dried. Crystallization from dilute alcohol afforded 6-chloro-7-sulfamyl-1,2,4-benzothiadiazine-1,1-dioxide as colorless needles, MP 342.5° to 343°C, as described in U.S. Patent 2,BOB,194. 

Chlorothiazide Chlorothiazide, 1,1-dioxide 6-chloro-2//-l,2,4-benzothiadiazin-7-sulfon-amide (21.3.3) is synthesized in the exact same manner, is aU thiazide diuretics. 3-Chloroanihne (or 3-trifluoromethylaniline) undergoes sulfoylchlorination by chlorosulfonic acid, forming 4,6-sntfonochloride-3-chloroanihne (21.3.1), the reaction of which with ammonia gives 4,6-sutfonylamido-3-chloroaniline (21.3.2). Heating this with formamide leads to formation of chlorothiazide (21.3.3) [9-11]. 

The photocatalytic degradation of widely used herbicides such as 2,4-D (2,4-dichlorophenoxyecetic acid), 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), bentazon (3-isopropyl-1 H-2,l,3-benzothiadiazin-4(3H)-one 2,2-dioxide), S-tiazines, carbetamide ((R)-l-(ethylcarbamoyl)ethyl carbanilate), and monouron (3-(4-chlorophenyl)-l-methoxy-l-methylurea) in water have been... 

The benzothiadiazepine 1-oxides (550), formed by the reaction of the diaryl sulfoxides (549) with hydrazoic acid, rearrange on treatment with sodium hydroxide to give (551) (72CB757). The benzothiadiazine 1,1-dioxide (552) also undergoes base-induced ring expansion to give (553) (71JOC2968). 

Aminobenzenesulfonamides are ring closed directly to AH- 1,2,4-benzothiadiazine 1,1-dioxides (500) with a variety of carboxylic acids, employing polyphosphoric acid trimethylsilyl ester as the cyclization agent (83S851, 85JAP(K)6025984, 90JMC172l). 

C) Preparation of 3-Benzyl-6-Trifluoromethyl-7-Sulfarnyl-3,4-Dihydro-l,2,4-Benzothiadiazine-1,1-Dioxide - 6.4 grams of 5-trifluoromethyl-2,4-disulfamylaniline is dissolved in 12 ml of dioxane, 2.7 ml of phenylacetaldehyde and a catalytic amount of p-toluenesulfonic acid are added. After boiling for a short time under reflux, the reaction mixture crystallizes, and, after filtration and recrystallization from dioxane, the desired... 

To a mixture of 3.0 grams of N,N -diacetyl-o-anilamide and 20 ml of acetic acid is added a previously prepared solution of 1.5 grams of chlorine in 31 cc of acetic acid. The reaction mixture is allowed to stand at room temperature for 3 hours and is then evaporated to dryness on a steam bath under reduced pressure. The resulting solid residue is recrystallized from ethanol, yielding the intermediate N,N -diacetyl-2-sulfamyl-4-chloroaniline. The intermediate compound is fused in an oil bath at 250-260°C for 15 minutes, cooled and the product so obtained is crystallized from 80% ethanol yielding 3-methyl-7-chloro-1,2,4-benzothiadiazine-l,1-dioxide, MP 330°C. 

This intermediate is treated with an excess of 98% formic acid at steam bath temperature for 3 hours. Evaporation and dilution with water gives 7-sulfamyl-6-trifluoromethyl-l,2,4-benzothiadiazine-l,1-dioxide, MP 304°C to 308°C. 

The cyclization of the 0/7/fo-substituted aniline 487 with acetic acid and sodium nitrite affords 4,l,2-benzothiadiazin-3-carboxylate 4,4-dioxides 488 via diazonium salt intermediates (Scheme 255) <1996JHC347, CHEC-III(9.08.8.1)429>. 

To increase the marketability of Collego, its compatibility with chemical pesticides has been investigated. Mixtures of CGA with propanil [N-(3,4-dichlorophenyl)propanamide], molinate [S-ethyl hexahydro-lH-azepine-l-carbothioate], 2,4,5-T, and benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate] were detrimental to CGA s efficacy (31). If, however, propanil, 2,4,5-T, fentin hydroxide (triphenyltin hydroxide), pencycuron N-[(4-chlorophenyl)methyl]-N-cyclopentyl-N -phenylurea), each at 0.56 kg ai/ha, and SN-84364 [3 -isopropoxy-2-(trifluoromethyl) benzanilide] (at 0.40 kg ai/ha) were applied after CGA treatment, disease and development were not inhibited (32). The herbicides, acifluorfen 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid) (0.56 kg ai/ha) and bentazon [3-(1-methylethyl)-(IH)-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide] (0.56 to 1.1 kg ai/ha), or the insecticides, malathion [diethyl(dimethoxyphosphinothioylthio)succinate] (0.56 kg ai/ha) and carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate), (0.56 kg ai/ha) could be applied with CGA from a single tank mixture (33-34). ... 

CHLORO-7-SULFAMOYL-3,4-DIHYDRO-2H-l,2,4-BENZOTHIADIAZINE-l,l-DIOXIDE see CFYOOO CHLOROSULFONIC ACID see CLG500 CHLOROSULFONIC ACID (with or without sulRir trioxide) (UN 1754) (DOT) see CLG500 CHLOROSULFONIC ANHYDRIDE see PPR500... 

Francotte P, Goffin E, Fraikin P et al (2010) New fluorinated 1, 2, 4-benzothiadiazine 1, 1-dioxides discovery of an orally active cognitive enhancer acting through potentiation of the 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid receptors. J Med Chem 53 1700-1711... 

The HPLC characterization of the major 3,4-dihydro-2i/-l,2,4-benzothiadiazine 1,1-dioxide diuretics has been discussed in detail <85JC395>, and their racemic mixtures have been resolved into the pure enantiomers by liquid chromatography on a variety of stationary phases including chiral polyacrylamides (1 1 toluene-dioxan as eluant) <85JPS438>, (R)(-l-)-camphanic acid and V-(IS)-... 

Acid-catalyzed condensation of ethyl benzoylacetate with 2-aminobenzenesulfonamide yields the enamine (182), which, under basic conditions, is cyclized to 3-phenyl-2/7-l,2,4-benzothiadiazine 1,1-dioxide (183) in 65% yield (Scheme 29) <84JOU534, 84URP1074873, 87EJM157>. 

Methylation of the highly acidic l/f-2,l,3-benzothiadiazin-4(3//)-one 2,2-dioxide (112) at N-3 is readily achieved in 62% yield with dimethyl sulfate at room temperature <62JA1994> with an excess of reagent the 1,3-dimethyl derivative (114) is obtained in the same yield (Scheme 4). 

There are only a few examples of the oxidation of the divalent ring sulfur atom in 1,2,6-thiadiazines to the S-mono- and 5,5-dioxides. Oxidation of 1,2,6-thiadiazines and their 1-oxides to the 1,1-dioxides can be effected in high yields (71-75%) with w-chloroperbenzoic acid in chloroform solution at room temperature <8iJCS(Pi)l89i, 93JOC700). In contrast, similar oxidations of 3-aryl-4,5-dihydro-l//-2,l,3-benzothiadiazine 1-oxides (Section 6.16.9.2.2.2) yield only uncharacterized oily products <85TL2813>. 

Thiazide diuretics are found to be weakly acidic in nature having a benzothiadiazine 1,1-dioxide nucleus. 

Photolysis of an aqueous solution of Bentazone (3-isopropyl-17/-2,l,3-benzothiadiazin-4(3//)-one 2,2-dioxide, 5) with a solar simulator affords 2-aminobenzoic acid 90. The extinction coefficient at 300 nm was 1210 with a quantum yield of 2.0 x lO " (365 nm) (Equation 4) <2001FEB554>. 

Alkylation of 5-chloro-l,4-dihydro-2/7-A -2,l,3-benzothiadiazin-3-acetic acid 2,2-dioxide 99 with alkyl bromides using sodium hydride in dimethylformamide gave the corresponding 1-alkylated products 100 (Equation 6) <2001JMC1847>. 

While alkylation of an already monoalkylated 2,l,3-benzothiadiazin-4-one 2,2-dioxide is straightforward, alkylation of the unalkylated parent 110 is more complex. Considering the different acidity of the two nitrogen atoms (p.ATa 0.69, 7.95) <1999T12405>, the first chlorophenylmethyl fragment can be introduced in aqueous bicarbonate to give 111... 

Cyclization of methyl anthranilates with sulfamyl chloride affords 2,1.3-benzothiadiazin-4-ones (Section 9.07.9.1.1). The less common l//-2,l>3-benzothiadiazine 2,2-dioxides were obtained in modest yield by reaction of 2-hydroxymethyl anilines with Burgess reagent (Section 9.07.9.1.1). A two-step process starting from t>/t, <7-iodosulfamides, via generation of a trianion, condensation with an aldehyde, and subsequent acid-catalyzed cyclization, led efficiently to 4-substituted-3,4-dihydro-l//-2,l,3-benzothiazine 2,2-dioxides (Section 9.07.9.2.2). 

Synonyms 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide Chlorosulthiadil Chlorzide Dihydrochlorothiazide Empirical C7H8CIN3O4S2 Properties Wh. or pract. wh. cryst. powd., odorless sol. in sodium hydroxide sol n., dimethylformamide, dil. ammonia, NaOH insol. in water, chloroform, ether, dil. min. acids m.w. 297.75 m.p. 273-275 C Toxicology LD50 (oral, mouse) 2830 mg/kg poison by IP and IV routes mod. toxic by ing. and subcutaneous routes mutagenic data diuretic TSCA listed... 

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