Heterocyclic Building Blocks-Isothiazole

Schwenker, Gerhard’s team published research in Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft in 303 | CAS: 7668-28-2

Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft 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 C7H7IN2O, Synthetic Route of 7668-28-2.

Schwenker, Gerhard published the artcileInfrared spectroscopic studies of tautomerizable amidines. I. N-sulfonylamidines and 3-amino-1,2-benzisothiazole 1,1-dioxides, Synthetic Route of 7668-28-2, the publication is Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft (1970), 303(12), 980-7, database is CAplus and MEDLINE.

According to ir spectroscopic data, open-chained N-sulfonylamidines and amino-benzisothiazole 1,1-dioxides exist in the crystalline state and solution in the amino form R2SO2N:CR3NRR1 (I) and II, resp. The bathochromic shift of the SO2 and C:N stretching bands and investigation of the N-H region indicate that the SO2 group is involved in the amidine mesomerism and that intramol. H bonds are present in I. Investigated were the following I (R, R1, R2, and R3 given): H, H, Me, Me; H, H, Ph, Ph; H, H, C6H4Me-p, Ph; H, Me, C6H4Me-p, Ph; H, Ph, C6H4Me-p, Ph; H, H, C6H4NO2-p, Me; H, H, C6H4NO2-p, Ph; H, Me, C6H4-NO2-p, Ph; H, H, C6H4NH2-p, Ph; H, H, C6H4NHAc-p, Ph; and II (R and R1 given): H, H; H, Me; H, C6H13; H, cyclohexyl; H, Ph; (RR1 = ) (CH2)5.

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

Chen, Yantao’s team published research in ACS Medicinal Chemistry Letters in 8 | CAS: 7668-28-2

ACS Medicinal Chemistry Letters 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.

Chen, Yantao published the artcileSaccharin Aza Bioisosteres-Synthesis and Preclinical Property Comparisons, Product Details of C7H6N2O2S, the publication is ACS Medicinal Chemistry Letters (2017), 8(6), 672-677, database is CAplus and MEDLINE.

Methods are disclosed for the preparation of azapseudosaccharins such as I and exo- and endo-N-substituted azasaccharins such as II; the pharmacokinetics (plasma protein binding, clearance, permeation through biol. membranes), physicochem. properties (lipophilicity, acidity, solubility in DMSO) and hERG binding were determined for selected (matched-pair) compounds Exo- or endo-N-substituted azasaccharins were prepared chemoselectively using primary amines by controlling the order of desilylation and cyclization reactions. The effect of sulfur stereochem. on the crystal structures and biol. properties of exo-N-substituted azasaccharins was studied in assays and using DFT calculations The structures of II and its diastereomer at sulfur were determined by X-ray crystallog.; the differences in crystal structure, solubility, and NMR chem. shifts were studied using DFT calculations

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

Inagaki, Masanao’s team published research in Journal of Organic Chemistry in 2002-01-11 | CAS: 73343-04-1

Journal of Organic Chemistry published new progress about ditertbutylhydroxybenzylideneethylisothiazolidine dioxide preparation; isothiazolidine ditertbutylhydroxybenzylideneethyl dioxide preparation. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Application In Synthesis of 73343-04-1.

Inagaki, Masanao published the artcileHighly E-Selective and Effective Synthesis of Antiarthritic Drug Candidate S-2474 Using Quinone Methide Derivatives, Application In Synthesis of 73343-04-1, the main research area is ditertbutylhydroxybenzylideneethylisothiazolidine dioxide preparation; isothiazolidine ditertbutylhydroxybenzylideneethyl dioxide preparation.

We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474), in which α-methoxy-p-quinone methide is used as a key intermediate. α-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with α-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Inagaki, Masanao’s team published research in Journal of Medicinal Chemistry in 2000-05-18 | CAS: 73343-04-1

Journal of Medicinal Chemistry published new progress about Antiarthritics. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Formula: C5H11NO2S.

Inagaki, Masanao published the artcileNovel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase, Formula: C5H11NO2S, the main research area is antiarthritic isothiazolidine dioxide sultam preparation; structure activity antiarthritic isothiazolidine dioxide sultam.

Various 1,2-isothiazolidine 1,1-dioxide (γ-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared Some compounds, which have a lower alkyl group at the 2-position of the γ-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474) (I) was selected as an antiarthritic drug candidate and is now under clin. trials. The structure-activity relationships (SAR) examined and some pharmacol. evaluations are described.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Oda, Katsuo’s team published research in Organic Process Research & Development in 2008-06-30 | CAS: 73343-04-1

Organic Process Research & Development published new progress about Antiarthritics. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Product Details of C5H11NO2S.

Oda, Katsuo published the artcileDevelopment of One-Pot Synthesis of New Antiarthritic Drug Candidate S-2474 with High E-Selectivity, Product Details of C5H11NO2S, the main research area is antiarthritic drug candidate S2474 high E selectivity preparation.

A one-pot synthesis of S-2474 was developed to overcome the problems of a large number of steps, low stereoselectivity, low yield, a large amount of waste, and severe reaction conditions. Aldol-type condensation of 3,5-di-tert-butyl-4-hydroxybenzaldehyde and N-ethyl-γ-sultam was carried out with LDA and then quenched with water. Dehydration proceeded under basic conditions, providing S-2474 directly as a single isomer on the benzylidene double bond. The reaction mechanism appears to involve a quinone methide intermediate. Environmental assessment of the development of this compound is also discussed.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Kocevar, Marjan’s team published research in Monatshefte fuer Chemie in 1982-07-31 | CAS: 56891-64-6

Monatshefte fuer Chemie published new progress about Cyclocondensation reaction. 56891-64-6 belongs to class isothiazole, name is Isothiazolo[5,4-b]pyridin-3-amine, and the molecular formula is C6H5N3S, Synthetic Route of 56891-64-6.

Kocevar, Marjan published the artcileNeighboring group participation in formation of condensed azines. Formation of pyrazolo[3,4-b]pyrazines, isoxazolo[4,5-b]pyrazines and isothiazolo[5,4-b]pyridine. Heterocycles. CCX, Synthetic Route of 56891-64-6, the main research area is neighboring group participation cyclization; azine condensed; pyrazine pyrazolo isoxazolo; pyrazolopyrazine; oxazolopyrazine; isothiazolopyridine; pyridine isothiazolo.

Pyrazine- and pyridinecarboxamidoximes with an amino or potentially tautomeric hydroxy or mercapto group in the ortho position were transformed into condensed azines. Representative pyrazolo[3,4-b]pyrazines, isoxazolo[4,5-b]pyrazines and isothiazolo[5,4-b] pyridine ring systems were synthesized and some transformations investigated.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Inagaki, Masanao’s team published research in Journal of Organic Chemistry in 2003-02-07 | CAS: 73343-04-1

Journal of Organic Chemistry published new progress about Oxidizing agents (hydrobromic acid-DMSO). 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Formula: C5H11NO2S.

Inagaki, Masanao published the artcileShort Synthesis of tert-Butyl-Hydroxylated 3,5-Di-tert-butyl-4-hydroxybenzaldehyde: Synthesis of tert-Butyl-Hydroxylated S-2474, Formula: C5H11NO2S, the main research area is hydroxybenzaldehyde hydroxybutyl preparation; oxidizing agent hydrobromic acid DMSO; antiarthritic drug S2474 metabolite preparation.

We have developed a very short synthesis of tert-butyl-hydroxylated di-tert-butyl-4-hydroxybenzaldehyde (I) in which the HBr-DMSO system is used as an effective oxidant (overall yield of 45% for the entire four-step process from 2-tert-butyl-p-cresol). We also accomplished the synthesis of a major metabolite (II) of the antiarthritic drug candidate S-2474.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Lewis, Sheldon Noah et al. published their patent in 1969 |CAS: 26172-54-3

2-Methylisothiazol-3(2H)-one hydrochloride(cas:26172-54-3) belongs to isothiazoles. Isothiazoles and benzisothiazoles are usually liquids or low-melting-point solids; polar substituents increase the melting points because of the possibility of hydrogen bonding and other interactions in the crystalline state.Computed Properties of 26172-54-3

On January 24, 1969, Lewis, Sheldon Noah; Miller, George Allen published a patent.Computed Properties of 26172-54-3 The title of the patent was Pesticidal 3-isothiazolones and 3-hydroxyisothiazoles. And the patent contained the following:

The title compounds (I) and (II) showing-interesting activity against bacteria, algae, and mycetes are prepared by cyclization of appropriate dithiodipropionamides. To a mixture of 20.8 g (SCH2CH2CONH2)2 in (CH2Cl)2 at 10-5° was added dropwise over 2 hr 42.5 g SO2Cl2, the mixture then kept at 25-30° f or 16 hr, to give 4 g I (R1 = H, R2 = Cl) (II), m. 95-6°. Continuous extraction of the aqueous filtrate with Et2O gave 11.1 g I (R1 = R2 = H), m. 75-6° (C6H6-hexane). Similar treatment of 70.9 g (SCH2CH2CONHMe)2 with 121.5 g SOCl2 in 1 l. (CH2Cl)2 gave 37.1 g. insoluble III (R1 = Me, R2 = R3 = H).HCl (IV) from which the base could be obtained by extraction from H2O with Et2O. Concentration of the organic filtrate gave after filtration 30.5 g less pure IV, and the filtrate finally gave 24.7 g oil sublimed at 40-60°/l mm to yield 11.5 g III (R1 = Me, R2 = H, R3 = Cl), m. 44-7°. By similar methods were prepared III (R1 = 3,4-Cl2C6H3, R2 = Me, R3 = H), m. 161-3° (AcOEt), III (R1 = CONHEt, R2 = R3 = H), m. 97-101° (C6H6-ligroine), I (R1 = Me, R2 = Cl), m. 122°, and I ( R1 = Me, R2 = H), m. 100-50° (from dithiodiisobutyra-mide). To a solution of 6.8 g II in 100 ml AcOEt at 0° was added 8 g Br in 25 ml AcOEt. The mixture was allowed to reach room temperature to give 8.7 g I (R1 = Br, R2 = Cl), m. 145-7°. Treatment of 5.1 g II in 100 ml AcOEt with 6.75 g SOCl2 over 20 mi n at 60° gave 3.2 g I (R1 = R2 = Cl), m. 151-4° (C6H6-EtOH). The experimental process involved the reaction of 2-Methylisothiazol-3(2H)-one hydrochloride(cas: 26172-54-3).Computed Properties of 26172-54-3

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Lewis, Sheldon Noah et al. published their patent in 1969 |CAS: 26172-54-3

The Article related to antibacterial isothiazolinone, isothiazolinone antibacterial, pesticidal isothiazolinone, urea pesticidal, carbamoyl isothiazolinone, phenyl carbamoyl isothiazolinone, antibacterial agents, fungicides and other aspects.SDS of cas: 26172-54-3

On January 24, 1969, Lewis, Sheldon Noah; Miller, George Allen; Law, Andrew B. published a patent.SDS of cas: 26172-54-3 The title of the patent was Pesticidal substituted 3-isothiazolinones. And the patent contained the following:

The title compounds (I) were prepared Thus, 0.05 mole 3-hydroxyisothiazole (II) in benzene and 0.05 mole (Me nCO) in a 50% benzene solution gave 70% I (R = H, R’ = H, Y = CON hMe), m. 138-40°. II with MeNCS gave I (R = H, R’ = H, Y = C(:S)NHMe), m. 155-8°. Similar I prepared were (R, R’, Y, and m.p. [of salt if shown] given): H, Me, CONHCH3, 138-45°; Br, Me, CONH-CH3, 191-5°; CN, SCH3, CONHCH3, 207-10°; CN, SOCH3, CONHCH3, 158-60°; CN, SO2CH3, CONHCH3, 146-50°; H, H, CONHBu, oil; H, H, CONHC8H17-tert, oil; H, Me, CONHC6H5, 142-6°; CN, SCH3, CONHC6H5, 183-6°; Br, Me, CONHC6H4Cl-3, 200-2°; H, CH2Br, CONHC6H4Cl-3, 178-80°; H, Me, CONHC6H4Cl-3, 142-4°; CN, SCH3, CONH-C6H4Cl-3, 192-4°; H, H, CONHC6H4Cl-3, 120-3°; H, Me, CONHC6H4Cl-2, 162-4°; H, CH2Br, CONHC6H4Cl-2, 199-201°; Br, Me, CONHC6H3Cl2-3,4, 235-7°; H, Me, CONHC6-H3Cl2-3,4, 195-207°; CN, SCH3, CONHC6H3Cl2-3,4, 118-20°; H, Me, CONHSO2C6H4CH3-4, 170-3°; CN, SCH3, CONHSO2-C6H4CH3-4, 163-8°; Br, Me, CONHSO2C6H4CH3-4, 199-203°; H, H, CONHC2H5, 103-5°; H, H, CONHCPr, 84-8°; H, H, CONHPr-iso, 53-6°; Br, H, CONHCH3, 194-7°; H, H, CONHC6H4OCH3-4, 134-7°; H, H, CONHC6H4OCH3-2, 140-5°; H, H, CONHC6H4NO2-3, 195-8°; H, H, CONHC6H3-Cl-4, 172-4°; H, H, CONHC12H25, 60-2°; H, H, CONHC6H3-Cl2-2,5, 179-80°; H, H, CONHCH2CO2C2H5, 80-3°; H, H, CONHC6H4NO2-4, 225-30°; H, Me, CONHC2H5, 53-6°; H, Me CSNHC2H5, 73-103°; H, Cl, CONHC2H5, 53-5°; H, H, Pr, 65-8°; H, H, tert-Bu, 75-9°; H, H, Bu, 99°; H, H, C6H11, 109-11°; H, H, tert-C8H17, 97-100°; H, H, CH2C6H5, 78-80°; H, Cl, Me, 44-7°; H, Cl, CH2C6H5, 57-9°; Cl, Cl, Me, 114-17°; Me, H, Me, 58-68°; Me, H, C6H3Cl2-3,4, 161-3°; H, H, C6H3Cl2-3,4, 131-3°; Cl, Cl, CH2C6H5, 62-4°; Br, Cl, Me, 86-7°; Br, H, Me, 94-7°; H, H, CH2OH, 124-6°; H, H, CH2CH2NEt2, oil; H, H, Pr, (HCl), 87-90°; H, Cl, Me, (HCl), -; H, H, Et, (HCl), 144-6°; H, H, Me, (HCl), 162-6°; H, H, CH2C6H5, (HCl), 147-53°; H, H, n-C12H25, 46-9°; H, H, n-C14H29, 53-5°; H, H, CH2C6H4Cl-4, 87-8°; H, H, CH2C6H4Cl-2, 99-100°; H, H, CH2C6H3Cl2-2,4, 122-4°; H, H, CH2C6-H3Cl2-3,4, 87-9°; H, H, CH2C6H4OCH3-4, 80-2°; H, H, CH2C6-H4CH3-4, 76-7°; H, H, CH2CH2C6H5, 76-8°; H, Cl, CH2CH2-C6H5, 55-9°; H, H, n-C10H21, 41-2°; Cl, H, tert-C8H17, 137-40°; Br, H tert-C8H17, 138-42°; H, H, n-C9H19, 30-1°; H, Cl, n-C8H17, oil; H, H, C6H4NO2-4, 170-5° (decompn); H, H, C6H4CO1C2-H5-4, 141-2°. Similarly prepared were I as follows (R, R’, Y, and b.p. given): H, H, CH2CH(Bu)(Et), b0·005 119-20°; H, H, CH(Me)(Ph), b0·003 138-40°; H, H, n-C8H17, b0·01 120°. The compounds are fungicides, bactericides, insecticides, nematocides, and miticides, effective against many common species. The experimental process involved the reaction of 2-Methylisothiazol-3(2H)-one hydrochloride(cas: 26172-54-3).SDS of cas: 26172-54-3

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Hoss, Gerhard et al. published their patent in 1992 |CAS: 26172-54-3

The Article related to preservative diagnostic reagent solution, Biochemical Methods: Reagents and other aspects.Safety of 2-Methylisothiazol-3(2H)-one hydrochloride

On January 22, 1992, Hoss, Gerhard; Pappert, Gunter; Schmidt, Axel published a patent.Safety of 2-Methylisothiazol-3(2H)-one hydrochloride The title of the patent was Preservation of diagnostic test reagents and kits. And the patent contained the following:

Diagnostic test kits and the reagents therein are preserved from microbial degradation by a combination of ≥2 of 2-methyl-4-isothiazolin-3-one-HCl, 2-hydroxypyridine N-oxide, chloroacetamide, N,N-methylenebis[N-(1-hydroxymethyl)-2,5-dioxo-4-imidazolidinyl]urea (I), and 5-bromo-5-nitro-1,3-dioxane. Thus, the reagents in a kit for automated determination of albumin (succinate buffer, pH 4.2; bromcresol green; Brij 35; and preservatives 2-hydroxypyridine N-oxide and I) were incubated with a mixture of bacteria, fungi, and yeasts for 6 wk at 23°. After this time, the bacterial count was reduced by 1.6 x 104 and the count of fungi and yeasts by 8.3 x 104. The experimental process involved the reaction of 2-Methylisothiazol-3(2H)-one hydrochloride(cas: 26172-54-3).Safety of 2-Methylisothiazol-3(2H)-one hydrochloride

The Article related to preservative diagnostic reagent solution, Biochemical Methods: Reagents and other aspects.Safety of 2-Methylisothiazol-3(2H)-one hydrochloride

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com