2- one 1,1-dioxide

Individual aspects of nitrile oxide cycloaddition reactions were the subjects of some reviews (161 — 164). These aspects are as follows preparation of 5-hetero-substituted 4-methylene-4,5-dihydroisoxazoles by nitrile oxide cycloadditions to properly chosen dipolarophiles and reactivity of these isoxazolines (161), 1,3-dipolar cycloaddition reactions of isothiazol-3(2//)-one 1,1-dioxides, 3-alkoxy- and 3-(dialkylamino)isothiazole 1,1-dioxides with nitrile oxides (162), preparation of 4,5-dihydroisoxazoles via cycloaddition reactions of nitrile oxides with alkenes and subsequent conversion to a, 3-unsaturated ketones (163), and [2 + 3] cycloaddition reactions of nitroalkenes with aromatic nitrile oxides (164). 

Methylisothiazolo[5,4- ]pyridin-3-(2//)-one-l-oxide 103 was quantitatively obtained by treating 104 with chlorine in aqueous acetic acid (Equation 13). The oxidation of 104 with Oxone at 60 °C in aqueous methanol gave 2-methylisothiazolo[5,4- ]pyndin-3-(2//)-one 1,1-dioxide 105 in a single step (Equation 14). No C-halogenation or N-oxidation products were detected under these reaction conditions <1996T8947>. 

In the attempted synthesis of isothiazolo[5,4-3]pyridin-3(2//)-one 1,1-dioxide 172, direct oxidation of isothi-azolo[5,4-/ ]pyridin-3(2//)-one with either Oxone /MeOH, 3-chloroperoxybenzoic acid/CH2Cl2, or KMn04/AcOH did not afford the desired product. However, this compound was synthesized in good yield by treatment of 173 with chlorine in aqueous HCl and subsequent reaction with ammonia in ethanol (Scheme 14) <1996T8947>. 

Cyclic imidates (208 X = 0) and thioimidates (208 X = S) react with ketene in sulfur dioxide to give oxazolo[2,3-6]thiazol-3(2//)-one 1,1-dioxide (210 X = 0) and the corresponding thiazole analog. It appears possible that the reaction produces as the initial product the open-chain 1,3-dipole (209), which is not octet-stabilized (69JHC729). 

The sulfur in 1,2-dithiolanes is nucleophilic and can be alkylated to form 1,2-dithiolanium salts (527 528). S-Oxidation and/or formation of sulfones of thiazolidines results in certain situations, for example, with penams <2001BMC2113>. Pyrolysis of thiazolidin-2-one 1,1-dioxides results in loss of SO2 and the formation of -lactams < 1997J (P 1)2139 >. 

Starling compound is prepared from 2,5-bis(3, 4 -dimethylphenyl)-4-hydroxy-thio-phen-3(2//)-one 1,1-dioxide, which undergoes fragmentation in HOAc, NaOAc solution at IIO C. ... 

The synthesis and pyrolytic behavior of thiazolidin-2-one 1,1-dioxides have been studied. Extrusion of SO2 leads to the formation of /3-lactams as shown in Scheme 40 <1997J(P1)2139>. 

SNC, Thiocyanate, gold complex, 26 90 SNOjCjH, 1,2-Benzisothiazol-3(2//)-one 1,1-dioxide, chromium and vanadium complex, 27 307, 309 SOOsPCvH45. Osmium, carbonyl(thiocar-bonyl)tris(triphenylphosphine)-,... 

Saccharin 2, 1,2-benzisothiazol-3(2//)-one 1,1-dioxide, is one of the most well-known isothiazolone derivatives, which was first prepared by Remsen and Fahlberg in 1879 by an oxidative cyclization of ort/m-toluene-sulfonamide (1879CB469, 73AHC233, 85AHC105). 

The oxidation of salts 57,61-63 and 121,123 with H2O2/ACOH at room temperature gave the 3-hydroperoxysultams 239-243 and at 80 °C they directly reacted to the isothia/ol-3(2//)-one 1,1-dioxides 251-257 (method A). The elimination of water using ethanol and concentrated hydrochloric acid gave 3-oxosultams 251-257 (method B) as well as by reduction of 239-243 with Na2S03 via 244-247 (method C), respectively (Scheme 85). In Table 16, 3-hydroperoxysultams 239-243 and 3-oxosultams 251-257... 

The isothiazol-3(2//)-one 1,1-dioxides 254-257 with stabilizing aryl substituents in the 2-, 4- and/or 5-position are potential inhibitors toward human leukocyte elastase (HLE) (03ZN(B)111, 05JEIMC341). HLE is a serine protease implicated in several inflammatory diseases and represents a major target for the development of low-molecular weight inhibitors. 

Furthermore, oxidation of 402 and 403 with hydrogen peroxide furnished isothiazol-3(2//)-one 1,1-dioxides 404 and 405 (method B) as ring contraction products, which can be obtained directly by oxidation of imines 71 and 130 or perchlorates 73 and 132 (method A), respectively. The structures 402e (R = 4-Br), 404c (R = 3-N02) and 407b (R = 3-N02) were confirmed by X-ray diffraction (99JHC1081, Scheme 136). 

Proton NMR spectroscopic and dipole moment measurements indicate that the heterocyclic ring of 5-amino-4,4-dibenzyl-47f-l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (36) has the same planar structure in solution as in the solid state <88CJC2477>. 

Amino-4//-l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (48) has a monoclinic crystal structure with a flattened boat conformation. The SOz prow and the 4-CHz stern subtend angles of 27.5° and 25.3°, respectively, with the planar hull as defined by Nj—C3—C5—<86AX(C)892>. Boat conformations have also been determined for 4//-l,2,6-thiadiazine-3,5(2//,6//)-dione 1,1-dioxides (49 R = cycloQH, or Ph) <87CJC298>. 

Studies on the tautomeric equilibria of 3,5-diamino-4-hydroxyimino-l,2,6-thiadiazine 1,1-dioxides (79 R = H) and 5-amino-4-hydroxyimino-1,2,6-thiadiazin-3(2//)-one 1,1-dioxides (80) are also available <88Mi 6i6-oi>. On the basis of H, C, and N NMR studies it is concluded that in all instances, the oxime tautomers are preferred over the 4-nitroso- forms, and that the 3-ones exist as the lactams rather than the 3-hydroxy tautomers. In addition, for the diamino-oxime (79 R = H) and its 0-methyl ether (79 R = Me), the amino rather than the imino tautomer is dominant. In contrast, with the 5-amino-1,2,6-thiadiazinone 1,1-dioxides (80 R = H or PhCHj) there appear to be unquantified amounts of the imino tautomers (81) present. 

Halogenation of 5-methyl-2-phenyl-6//-l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (124) in chloroform solution, as shown in Scheme 8, furnishes the 4-halogeno-derivatives (125-127) <87MI 6I6-01, 88JCR(S)94), However, with bromine in hot acetic acid a mixture (50%) of the 4-bromo (125) and the 5-(bromomethyl) (128) derivatives is produced (Section 6,16,7.2) <88JCR(S)94>. 

Catalytic debenzylation of 2-benzyl-4-methyl-6 -l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (165) is effected in high yield (86%) with palladium-charcoal and hydrogen over a short period (1 h) <84CCC840>. However, on prolonged treatment (12 h) debenzylation is followed by reduction of the C-4—C-5 double bond and formation of 4-methyl-5,6-dihydro-4 -l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (166) (Equation (17)). 

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