1,3,4-Thiadiazines, review

The synthesis of this ring system by condensation of 3,4,5-triamino-l,2,6-thiadiazine-l,1-dioxide with formic acid equivalents to give the fused imidazole ring dates back to the review by Montgomery and Secrist <1984GHEC(5)607>. This methodology was extended to cyclocondensation reactions of 3,4,5-triamino-l,2,6-thiadia-zine-1,1-dioxide with electrophiles such as methyl chloroformate and carbon disulfide to yield 6-oxo 98 and 6-thioxo 99 derivatives of 4-aminoimidazo[4,5-d-l,2,6-thiadiazine-2,2-dioxide respectively (Scheme 72) <1999BMC1617>. 

A review on the synthesis of 1,3,4-thiadiazines and 1,3,4-oxadiazines shows the formation of the diones 105 and 106 (Equation 57) <1998H(49)557>. TPHA3 was preparedby treatment of 107 with DBU in air (Scheme 10) <1998JA2989,... 

Thiadiazines have been reviewed, in part, several times previously. A review of thiadiazine 1,1-dioxides covered the literature up until December, 1968 (70CRV593). The review did not include the very large number of... 

The IR spectrum of 8 has been reported (63FRP2166), and the UV spectra of some 1,2,3-benzothiadiazines have been reviewed (70CRV593). Mass spectrometry has been used to establish the structure of 1,2,3-thiadiazines 24, and the fragmentation pattern enabled the alternative isothiazol-N-imines to be ruled out (750MS579). 

Thiadiazines 1,1-dioxides, which include the sulfamide moiety, are not included here since they have already been reviewed (88AHC81). 

R. E. Busby has written a chapter on thiadiazines containing adjacent sulfur and nitrogen ring atoms. This chapter complements one in Volume 44 which dealt with sulfamides of this type. H. Quiniou and O. Guilloton of Nantes have covered the chemistry of monocyclic 1,3-thiazines, a group that, surprisingly, has not been reviewed comprehensively for many years. Finally, E. V. Kuznetsov and I. V. Shcherbakova of Rostov collaborate with A. T. Balaban of Bucharest in a summary of the chemistry of benzo[c]pyrylium salts. This review complements the review by a group of authors under the leadership of Balaban who covered the chemistry of pyrylium salts in Supplement 2 of this series, which appeared in 1982. 

Carbon-13 NMR assignments have been made for some of the ring systems under review. Comprehensive data are available for the 2,2-dioxides of pyrazino[2,3-c][l,2,6]thiadiazines (19)... 

Table 3) are described in the literature although the rarer 1,3,2- and 1,5,2-isomers are only known as the fully oxidized tetraoxides. Oxadiazines (Table 4) of all six types are reported, four of the isomers having an extensive and well established chemistry. The 1,2,3-and 1,2,6-isomers have been reported, but there is no spectroscopic evidence to support either structure. All the six isomeric thiadiazines (Table 5) are known with only the 1,5,2-isomer being poorly described. In line with the oxadiazines and thiadiazines being the most well known ring systems containing three heteroatoms, they are also the most well reviewed to date. 

Ring-contraction reactions of 6//-l,3,4-thiadiazines 167 (or their tautomeric forms) were widely used for the preparation of pyrazoles 168 (Scheme 47 and Table I) (for reviews, see 69ZC361 70MI1 87MI1 91KGS1443). 

Thiadiazines containing the 1,2-802 NH— moiety in the ring have been reviewed [3904]. 

The 2-Af-hydroxysulphonamidoaniline (19.4) reacts with DMAD or with 4-nit-robenzaldehyde to give this fused ring the chemistry of l,2..Y-thiadiazines, has recently been reviewed [3904]. 

An aza-Wittig reaction may be adapted to the synthesis of a fused thiadiazine ring under mild conditions with a two-molar proportion of an isothiocyanate. The reactions of isothiocyanates have been reviewed [3990]. In this way, an iminophosphorane is annulated to a neighbouring sp ring-carbon atom. 

A reactive side-chain methylene condenses with a nitroso group in a basic medium in this example, the methylene is joined to the ring through a sul-phonamide group. The chemistry of thiadiazines containing adjacent S and N atoms has been reviewed [3904J. 

Thiadiazines have been the subject of numerous review articles.1 In this section, only the formally aromatic or antiaromatic thiadiazines of the types A, B, D, and E are discussed. On the basis of formula C2, the 1,2,5-thiadiazines may be considered as antiaromatic compounds, but their chemistry involves mainly the hydrogenated derivatives and is therefore not included here. 

Formal condensation of a benzene ring onto a 1,3,4-thiadiazine, a 1,2,4-thiadiazine, a 1,2,6-thiadiazine, or a 1,2,5-thiadiazine leads to the benzothiadiazine structures G-J. Two benzo derivatives of 1,2,3-thiadiazines are known 1,2,3-benzothiadiazine (K) and 3,1,2-benzothia-diazine (L). Both benzo derivatives occur mainly as, S,S-dioxides for review articles see refs 1 and 2. 

The 1,2,3-thiadiazines (7) are still uncommon and are known mainly as the 5,5-dioxides of their hydro derivatives likewise for the 2H- and 4//-1,2,3-benzothiadiazine systems (8). 2H-, 2,3-Benzothiadiazines (8) are now accessible as the 3,4-dihydro derivatives by thermally induced [4 H- 2] cycloadditions of azodicarboxylates to benzothietes (see Section 6.13.7.2.2) <86TL5703>, whereas 4/7-3,1,2-benzothiadiazines (9) are unknown. 1,2,3-Thiadiazines in which sulfur is four-valent do not appear to have been prepared, nor do 1-thionia systems. The chemistry of 1,2,3-thiadiazines and 1,2,3-benzothiadiazines has been reviewed <90AHC(50)255>. 

As with the 1,2,3-oxadiazines and 1,2,3-thiadiazines discussed in Chapter 6.13 there appear to be no examples of the fully conjugated l-oxonia-(ll X = 0) and l-thionia-(ll X = S) systems. The chemistry of 1,2,4-thiadiazines and 1,2,4-benzothiadiazines has been reviewed <90AHC(50)255>. 

The chemistry of 1,2,5-thiadiazines and 2,1,4-benzothiadiazines has been reviewed <90AHC(50)255>. 

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>. 

UV Spectroscopy has been instrumental in determining not only the tautomeric nature of 1,2,6-thiadiazine 1,1-dioxides and their oxo-derivatives, but also the site of alkylation and glycosylation of these systems and of 1,2,6-thiadiazine 1,1-dioxides fused to other heterocyclic rings, for example pyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides. A detailed account of these studies is available <88AHC(44)8l>, as is a brief review on the UV spectra of 1,2,6-thiadiazine 1,1-dioxides <70CRV593>. 

The comprehensive review by Aran et al <88AHC(44)8l> should be consulted for details of other PMR data on 1,2,6-thiadiazine 1,1-dioxides and on 1,2,6-thiadiazine 1,1-dioxide systems fused to other heterocyclic rings. 

The synthesis of 2-amino-6//-l,3,4-thiadiazines (276) by condensation of a-haloketones (274) with thiosemicarbazides, as first reported by Bose <25JIC51,25JIC95) continues to be used as a reliable route to this system. The reaction, however, can be complex and the products are dependent on the nature of the substituents in each of the reactants, the polarity of the solvent used, and the reaction temperature <91CHE666> common by-products are 2-hydrazinothiazoles (275) and 3-amino-thiazolines (see Section 6.17.5.2). An excellent review of the confusing and sometimes erroneous pioneering work on these reactions is available . 

Since the review by R. K. Smalley in the CHEC-II(1996) <1996CHEC-II(2)783>, approximately a thousand new publications have appeared in the literature, wherein a mention of 1,3,5-oxadiazines or 1,3,5-thiadiazines has been made. This chapter serves as an update to this earlier review. Apart from the ring systems mentioned in CHEC-11(1996), the other common systems encountered in publications over the last decade are shown (1-5). 

No reactions of oxa- or thiadiazines with carbon or phosphorus nucleophiles or with electrophiles at nitrogen were reported during the time period of this review. 

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