1,2,4-Benzothiadiazine 5-oxides

The benzothiadiazine oxides (148) are formed by an unusual [4+2] cycloaddition reaction between the sulphinyl anilines (146) and the... 

Reaction of hydrazoic acid with the monoaryl sulphoxides (345) affords benzothiazine oxides (346) and benzothiadiazepine oxides (347), and the same reagent converts the diaryl sulphoxides (348) into the benzothiadiazine oxides (349), which undergo a base-catalysed rearrangement to (350), cf. (228) - (229a). JV-5-Alkylation of the latter occurs on treatment with sodamide and alkyl halides, and reduction of the lactam moiety is brought about by LiAlH4. ... 

Chloro-4//-l,2,4-benzothiadiazine 1,1-dioxides have been made from the oxo or hydroxy derivatives [90AHC(50)256 91CHE343]. Reaction of 27/-1,2,4-benzothiadiazine 1-oxides (106) with chlorine formed the S-chloro products [90AHC(50)256]. 

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). 

Fully saturated systems can be oxidized to the corresponding didehydro derivatives. For example, oxadiazine (83) gives (84) on oxidation with mercury(II) oxide (78KGS1208), and oxidation of (85) with DDQ gives the 3ff-2,l,3-benzothiadiazine dioxide (86), which can also be represented as the dipolar form (22) (79JHC1069). 

Very few examples of electrophilic attack at sulfur(II) have been reported for these systems, with the exception of oxidation. Alkylation of the benzothiadiazine (88) with trimethyloxonium tetrafluoroborate gave a poor yield of the imino ether (89). The major product (90) resulted from alkylation at sulfur followed by hydrolytic ring opening of the resulting azasulfonium salt (79JCR(S)214). 

Electrophilic sulfur species such as thionyl chloride are frequently used in the synthesis of sulfur-containing heterocycles and, for example, reaction with N-N 1,5-dinucleophiles is a direct route to 1,2,6-thiadiazine 1-oxides. Thus the thiadiazines (138 n-1) are readily prepared by treatment of (231) with thionyl chloride in pyridine (81JCS(Pl)l89l), and the benzothiadiazine (232) is similarly made from (233) (64JOC2717). Reaction of (234) with thionyl chloride gives the dithiatriazine (235) (74ZOR488). 

Carbomethoxyamino-2,l,4-benzothiadiazines, such as 192, can be made by the action of methyl isothiocyanatomethanoate on 2-nitroaniline, followed by reductive ring-closure with sodium dithionite. Oxidation with 3-chloroperbenzoic acid gives the corresponding 2-oxide 193 (71-... 

Benzothiazol 6-Chlor-2-(4-chlor-anilino)- E8b, 933 (3-NHR-2H-1,2,4-benzothiadiazin-l -oxid/Zn)... 

Dihydro-l//-2,l,3-benzothiadiazine 2,2-dioxide (46) has been oxidized to 3//-2,l,3-benzothiadiazine 2,2-dioxide (47) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (Scheme 6). The oxidation may also be carried out by irradiating a solution of the dihydro compound while adding bromine. With N-bromosuccinimide (NBS), and if substituents are not present in the 6- or 8-position, bromination occurs prior to oxidation (79JHC1069). 

The. V-alkyl-1 //-4.1,2-benzothiadiazin-2-amines 10 can be prepared in a one-pot process from l-alkyl(aryl)-l-phenylthiosemicarbazides by oxidative ring closure.121... 

The first synthesis of a 1 HA, 2,4-benzothiadiazine 1-oxide and simultaneously of the first cyclic sulfoximine were reported in 1964. 22 1 //-1,2,4-Benzothiadiazines were later prepared123 by reaction of S-(2-aminophenyl)sulfoximine 1 with cyanogen bromide to give 1//-1,2,4-thiadi-azin-3-amine 1-oxide 2a. Compounds 1 also react with phosgene to yield 1//-1,2,4-benzo-thiadiazin-3-amine 1-oxides 2b and c.123 An alternative route to 1 H-, 2,4-benzothiadiazine 1-oxides from sulfoximines and C-synthons has also been reported. 24 128... 

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