Heterocyclic Building Blocks-Isothiazole

Renwick, A. G. published the artcileThe fate of saccharin impurities: the metabolism and excretion of 3-amino[3-¹⁴C]benz[d]isothiazole-1,1-dioxide and 5-chlorosaccharin in the rat, COA of Formula: C7H6N2O2S, the publication is Xenobiotica (1978), 8(8), 487-94, database is CAplus and MEDLINE.

Most (87% of dose) of the 3-aminobenz[d]isothiazole 1,1-dioxide (I) [7668-28-2] (25 mg/kg, orally) was eliminated in the urine of rats within 24 h, 99% of which was unchanged I. 5-Chlorosaccharin [29083-16-7] (80 mg/kg, orally) administered to rats was excreted unchanged, with 76% dose in urine after 24 h, and only 4% in feces. There was <0.5% hydrolysis. Partition experiments indicated that chlorsaccharin had a polarity similar to saccharin, whereas I was more lipophilic, this being reflected in the extent of absorption from the gut and their metabolism

Xenobiotica published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, COA of Formula: C7H6N2O2S.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Nelson, James J. published the artcileQuantitation of o- and p-sulfamoylbenzoic acids in commercial saccharin by high speed liquid chromatography, Related Products of isothiazole, the publication is EDRO SARAP Research Technical Reports (1976), Paper 45-74, 25 pp., database is CAplus.

A 6 g saccharin [81-07-2] sample was dissolved in 30 mL MeOH, 1.6 mL HNO₃ was added, and the mixture was chilled and centrifuged. The precipitate was shaken with 10 mL MeOH and centrifuged. The supernatant was dried under N, mixed with 0.2 mL MeOH, and again dried. An internal standard (p-hydroxybenzoate) was added and the material was subjected to high speed liquid chromatog. on a Dupont SAX column with 0.008M NaNO₃ in 0.01M Na tetraborate buffer as the mobile phase. O-sulfamoylbenzoic acid [632-24-6] and p-sulfamoylbenzoic acid [138-41-0] were quantitated with a UV detector and were determined accurately at the 80 and 25 ppm levels, resp. O-toluenesulfonamide [88-19-7], p-toluenesulfonamide [70-55-3], 1,2-benzisothiazoline-1,1-dioxide [936-16-3], and 3-amino-1,2-benzisothiazole S-dioxide [7668-28-2] were extracted from saccharin with Me₂CO and determined with an ODS column with isooctane as the mobile phase.

EDRO SARAP Research Technical Reports published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Related Products of isothiazole.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Nederlof, A. published the artcileChemistry of rhodanine and its derivatives. Preliminary communication, Product Details of C7H6N2O2S, the publication is Recueil des Travaux Chimiques des Pays-Bas (1962), 578-80, database is CAplus.

Impure 5-(2,4-dinitrobenzylidne)-3-ethylrhodanine, m. 133°, was prepared by condensing 3-ethylrhodanine with 2,4-dinitrobenzaldehyde. Refluxing the impure product with EtOAc gave the more pure compound and presumably I (R = Et), m. 252-2.5°. The addition of large quantities of p-MeC₆H₄SO₂Cl accelerated the formation of orange I (R = Et), as well as of I (R = CH₂CH:CH₂), m. 190.5-1°, and I (R = CH₂CO₂Et), m. 183-4°. These compounds reduced to readily autoxidized II (R = Et), light yellow, m. 155-7°, II (R = CH₂CH:CH₂), yellow, m. 121.5-3.5°, and II (R = CH₂CO₂Et), nearly colorless, m. 169-70°, resp. The “anil method” of rhodanine condensation gave purer compounds with higher yields. 3-Aminorhodanine reacted in boiling EtOH with p-nitrobenzaldehyde to give orange 3-amino-5-(p-nitrobenzylidene)rhodanine, m. 230-1°, not the yellow 3-(p-nitrobenzylidenamino)rhodanine as reported by Ueda and Ohta (CA 52, 401d).

Recueil des Travaux Chimiques des Pays-Bas published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Product Details of C7H6N2O2S.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Klarmann, Bodo published the artcileSaccharinimine, Synthetic Route of 7668-28-2, the publication is Chemische Berichte (1952), 162-4, database is CAplus.

Heating 10 g. o-OHCC₆H₄SO₂Cl with 80 cc. 30% aqueous NH₄OH 2 hrs. at 60° with shaking in a bomb and keeping the mixture 12 hrs. at 0° give 2.5 g. saccharinimine, m. 300°. When the reaction is carried out at 100°, 2 g. saccharin (I), m. 220°, is obtained. Warming 20 g. I with 100 cc. 30% aqueous NH₄OH 7 hrs. at 60°, keeping the mixture 12 hrs., and acidifying it give unchanged I. In this reaction o-HN:CHC₆H₄SO₂NH₂ is probably formed as an intermediate in which the CH(:NH) group is then oxidized to a C(:NH)OH group, followed by cyclization by splitting off of NH₃.

Chemische Berichte published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Synthetic Route of 7668-28-2.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Hettler, Hans published the artcileCharacterization of primary and secondary amines with pseudosaccharin chloride, Safety of 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Fresenius’ Zeitschrift fuer Analytische Chemie (1966), 220(1), 9-15, database is CAplus.

Pseudosaccharin chloride (I) treated with primary and secondary amines (RR’NH) gave amidine-type compounds (II) which were also obtained by reaction of amines with pseudosaccharin ethers (III). Methods used for the preparation were: (1) The pure amine or a solution [for sparingly soluble amines, solution in CO(NMe₂)₂ was used] was treated with I in an inert solvent (C₆H₆) and II precipitated by addition of H₂O; (2) A 2% aqueous solution of the amine was shaken with a solution of I in C₆H₆ until II separated; (3) II precipitated when an aqueous solution of the amine was treated with a dioxane solution of I; (4) Reaction of III with the amine in MeCN, gave II after several hrs. at room temperature Using these methods the tabulated derivatives were prepared The R_f values were determined by thin layer chromatography on silica gel using 85:15 C₆H₆-MeOH. R, R’, Method, M.p., % yield, R_f; H, Me, 2, 303° (MeOH), 52, 0.44; H, Et, 2, 286° (MeOH), 73, 0.47; H, CH₂CH₂OH, 1, 246°, (MeCN), 79, 0.375; H, (CH₂)₉Me, 1, 73°, (cyclohexane), 79, 0.87; H, (CH₂)₁₃Me, 4, 145° (MeOH), 100, 0.645; H, (CH₂)₁₇Me, 1, 142°, (Me₂CO), 92, 0.615; H, CH₂CH:CH₂, 2, 220° (Me₂CO), 63, 0.395; H, (CH₂)₆NH (pseudosaccharin group), 3, 350° (CO(NMe₂)₂), -, 0.0; H, tert-u, 1, 255° (MeOH), 46, 0.36; H, p-MeC₆H₄CH₂, 1, 228° (Me₂CO-petr. ether), 98, 0.48; H, cyclohexyl, 1, 258° (MeCN), 96, 0.395; H, Ph, 1, 324° (MeCN), 99, 0.435; Et, Et, 1, 215° (MeCN), 96.5, 0.36; cyclohexyl, cyclohexyl, 1, 259° (MeOH), 99, 0.660; Ph, Ph, 1, 260° (MeOH), 96, 0.715; CH₂CH₂OH, CH₂CH₂OH, 3, 165° (MeCN), 65, 0.275; H, H, 4, 312° (Me₂CO), 100, 0.35; H, NH₂, 1, 245° (MeOH), 100, 0.42; Piperidine reacted with I (method 4) to give 100% II (NRR’ = piperidino), m. 211° (MeCN). Morpholine (method 1) gave 87.5% II (NRR’ = morpholino), m. 234° (MeCN). Ph₂C:NOH (method 1) gave 73% (IV), m. 165° (MeCN).

Fresenius’ Zeitschrift fuer Analytische Chemie published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Safety of 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Whitehead, Calvert W. published the artcileReaction of saccharin with amines. N-Substituted-3-amino-1,2-benzisothiazole 1,1-dioxides, Computed Properties of 7668-28-2, the publication is Journal of Organic Chemistry (1960), 413-16, database is CAplus.

A number of CH:CH.CH:CH.C:C.C(NHR):N.SO₂ (I) were prepared for pharmacol. evaluation as diuretic or hypoglycemic agents. Method A. Saccharin (II) (0.1 mole) added to excess alkyl- or aralkylamine boiling at at least 130° (after initial salt formation, the II dissolved), the solution refluxed 8 hrs., the excess amine removed in vacuo, the residue treated with Et₂O, and the precipitate crystallized from EtOH or aqueous EtOH gave I. Method B. Pseudosaccharin chloride (Meadow and Reid, CA 37, 2360⁹) (0.05-0.10 mole) added portionwise to 2 equivalents appropriate amine in dioxane, the mixture heated 1 hr. on a steam bath, the dioxane removed in vacuo, the residue dissolved in dilute EtOH, the solution treated with C (if necessary), the filtered solution concentrated, cooled, and the precipitate crystallized gave I. The following I were prepared (R, m.p., % yield, method given): Me, 292° (decomposition), 25, B; CH₂CH₂OH, 238°, 31, A; Pr, 215°, 61, B; iso-Am, 166°, 20, B; (CH₂)₃NMe₂, 150° (C₆H₆), 41, A; 3-pyridylmethyl, 224° 55, A; cyclohexyl, 248°, 40, A; CH₂Ph, 209°, 55, A; CH₂CH₂Ph, 244°, 52, A; CH₂C₆H₄Me-p, 222°, 56, A; CH₂C₆H₄Me-m, 214°, 55, A; CH₂C₆H₄OMe-p, 209°, 46, A. II (0.10-0.20 mole) added to PhCl containing 1 equivalent appropriate amine, the mixture refluxed 8 hrs., the PhCl removed in vacuo, the residue acidified with dilute HCl, cooled, the precipitate collected, and recrystallized from dilute EtOH gave N-substituted-o-sulfamoylbenzamides, o-RHNO₂SC₆H₄CONHR’ (III). N-Methylsaccharin (IV) (Rice and Pettit, CA 49, 12365b) (0.05-0.10 mole) added to excess alkyl- or aralkylamine boiling at at least 130°, the mixture refluxed 8 hrs., the excess amine removed in vacuo, the residue treated with dilute HCl, the solution cooled, the precipitate collected, and recrystallized from dilute EtOH gave N-substituted-o-methylsulfamoylbenzamides. The following III were prepared (R, R’, m.p., % yield given): H, cyclohexyl, 196°, 21; H, CH₂Ph, 103°, 31; Me, cyclohexyl, 130°, 53; Me, CH₂Ph, 105°, 33; H, CH₂CH₂Ph, 108°, 20; H, CH₂C₆H₄OMe-p, 115°, 15; Me, CH₂C₆H₄Me-p, 104°, 49. II (18 g.) and 5 g. 100% N₂H₄.H₂O (V) in 250 ml. dioxane heated 5 hrs. on a steam bath, after the mixture became homogeneous the dioxane removed in vacuo, the crystalline residue collected, and the product crystallized from EtOH gave 16.5 g. o-H₂NO₂SC₆H₄CONHNH₂ (VI), m. 180° (decomposition) (EtOH). IV (20 g.) added to 150 ml. dioxane followed by 5 g. 100% V, the mixture heated 4 hrs. on a steam bath, the dioxane removed in vacuo, the residue dissolved in EtOH, the solution filtered, the filtrate concentrated to smaller volume, cooled, and the resulting precipitate crystallized from EtOH gave 17 g. o-MeHNO₂SC₆H₄CONHNH₂ (VII), m. 140°. VI (5 g.) warmed on a steam bath with 40 ml. Ac₂O until solution occurred, the solution allowed to stand overnight at room temperature, the excess Ac₂O removed in vacuo, the residue dissolved in EtOH, the solution concentrated to smaller volume, cooled, and the precipitate (3 g.) recrystallized from EtOH gave N-acetylsaccharin, m. 191°. VII (5 g.) warmed on a steam bath with 35 ml. Ac₂O, allowed to stand overnight at room temperature, worked up as above, and the product (3.5 g.) recrystallized from EtOH gave o-MeHNO₂SC₆H₄CONHNHAc, m. 164°.

Journal of Organic Chemistry published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C12H14O, Computed Properties of 7668-28-2.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Ashby, John published the artcileSaccharin: an epigenetic carcinogen/mutagen?, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Food and Cosmetics Toxicology (1978), 16(2), 95-103, database is CAplus and MEDLINE.

Saccharin [81-07-2] together with 4 of the impurities found in the com. material and a further 9 functional analogs gave neg. results in the Salmonella reverse mutation assay of Ames et al. and the cell-transformation assay of Styles. The significance of these and related in vitro results was evaluated within the context of the ability of com. saccharin to cause bladder cancer in rats and dominant lethal effects in mice. Particular, evidence that the carcinogenicity and the dominant lethal effect associated with saccharin may be mediated by an epigenetic mechanism is evaluated, as is the possible role played by impurities in the generation of these and other biol. effects. The case for separating carcinogens into 2 classes, namely those that operate by a genotypic mechanism and those that elicit their effects via an epigenetic mechanism, is discussed. The compounds evaluated in the current study were saccharin base, Na saccharin [128-44-9], o-toluenesulfonamide [88-19-7], o-sulfonamidobenzoic acid [632-24-6], 5-chlorosaccharin [29083-16-7], 3-iminosaccharin [7668-28-2], 6-chlorosaccharin [46149-10-4], 5-chlorobenzisothiazoline-1,1-dioxide [2515-75-5], 6-aminosaccharin [22094-62-8], 6-nitrosaccharin [22952-24-5], 3-chloro-ψ-saccharin [567-19-1], n3,6-dichloro-ψ-saccharin [15864-53-6], 3-dimethylamino-ψ-saccharin [22716-43-4], 3-piperidinyl-ψ-saccharin [7668-30-6] and 3-pyrrolidino-ψ-saccharin [53541-65-4].

Food and Cosmetics Toxicology published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com