1.2.6- thiadiazin-3-one 1,1-dioxides,

Extension of these studies to 4,5,6-trisubstituted-l,2,6-thiadiazin-3-one 1,1-dioxides (73 R = CbHii, Bu or Ph R = H or Br) reveals that in d -DMSO, pyridine, chloroform and methanol solution the hydroxy tautomer (74) is dominant. <88JCS(P2)859>, except for the 5-methyl-6-phenyl derivative which is a mixture of the amide and hydroxy forms (73 and 74 R = Ph, R = H). 

The most common ring systems discussed in this chapter are the l,2,6-thiadiazin-3-one 2,2-dioxides 1, the corresponding amino analog 2, and their benzologs 3 and 4. 

A rare example of the substitution of a thiadiazine ring is noted with 5-(4-chlorophenyl)-2-isopropyl-2//-1,2,4-thiadiazin-3(4//)-one 1,1 -dioxide (73), which with bromine in acetic acid at room temperature undergoes rapid bromination to the 6-bromo-derivative (74) in high yield (83%), presumably by an addition-dehydrobromination process (Equation (5)) <88S733>. 

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>. 

Spectroscopic studies on the tautomerism of 67/-l,2,6-thiadiazin-3(27/)-one 1,1-dioxide (75 R = H) and its 5-methyl derivative (75 R = Me), are hampered by their low solubility in the standard solvents. However, from a comparison of C NMR data, obtained in d -DMSO solution, with model compounds, it is concluded that they exist mainly as the 3-hydroxy-6//-tautomers (75). In... 

Alkylation of 5-methyl-5,6-dihydro-2/f-l,2,6-thiadiazin-3(47y)-one 1,1-dioxide (104) in the presence of strong base proceeds as expected at the amide nitrogen center N-2 (Equation (4)) <89JMC1024>. 

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)). 

Benzyl-4-methyl-6/7-l,2,6-thiadiazin-3(2i7)-one 1,1-dioxide (203) is obtained in poor yield (22%) by cyclization of the sulfamide (202) with thionyl chloride in dichloromethane containing a catalytic amount of dimethylformamide. Yields are much improved (61 %), however, with trimethyl-silyl iodide as the cyclization agent (Equation (25)) <84CCC840>. 

In Section II, the chemistry of 1,2,6-thiadiazine 1,1-dioxides and fused systems will be described, but no attempt has been made to cover all the literature dealing with benzothiadiazinones. Numerous derivatives related to the herbicide bentazone (3-isopropyI-lH-2,l,3-benzothiadiazin-4-one 2,2-dioxide) have been prepared and are described in various patents, which will not be included. The reactivity of bentazone and related 2,1,3-benzo-thiadiazinones has also been extensively studied (81AG(E)151). 

The antiparasitic activity of 3,5-diaminothiadiazine derivatives has been tested, the most active compound being the parent one (Ila) (86FES862). Some 4-nitro derivatives of 1,2,6-thiadiazine have shown antimalarial and trichomonicidal activity (86MI1). Benzothiadiazine dioxides have been claimed to act as sedatives and mild tranquilizers (66USP3278532). 

Only one example of a rearrangement was reported for A-acylatcd 5-AI (see also Scheme 35). Cleavage of 5-sulfamidoisoxazoles gave 1.2.6-thiadiazine 1,1-dioxides 98. Cleavage of 3-sulfamidoisoxazoles follows a similar pathway (79JOC4191) (Scheme 41). 

The chemistry of 1,2,6-thiadiazine 1,1-dioxides, and other heterocycles containing the sulfamide (—NHSO2NH—) fragment, have been reviewed by Spanish workers who have been extremely active in this field <88AHC(44)81>. 1,2,6-Thiadiazines, and their benzologues, other than the S,S-dioxides have also been reviewed <90AHC(50)255>. The herbicidal activity of 3-isopropyl-1/7-2,1,3-benzothiadiazin-4(3//)-one 2,2-dioxide (Bentazone 6, R = CHMej), an important commercial product has been appraised <89Cl(M)30>. 

With a-keto-esters, 3,4,5-triamino-2//-1,2,6-thiadiazine 1,1 -dioxide (171) yields only the 4-amino-l/7-pyrazino[2,3-c][l,2,6]thiadiazin-7(8//)-one 2,2-dioxides (176), as a result of regioselective attack of the more nucleophilic 4-aminosubstituent at the ketone carbonyl centre <88LA121). 

The anilide of 5-methyl-2-phenyl-6/7-l,2,6-thiadiazin-3(4//)-one-4-carboxylic acid 1,1-dioxide... 

A number of 1 /7-pyrido[2,3-c]-l,2,6-thiadiazin-4(3/7)-one 2,2-dioxides and 1 //-pyrido[4,3-c]-1,2,6-thiadiazin-4(3//)-one 2,2-dioxides, for example (403), display herbicidal properties <75USP392064i, 77USP4014888). Four 3-arylpyrido[3,4-e]-1,2,4-triazines (404a-c) and (252) have been studied as germination inhibitors <84Mi 717-03). 

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