1.2.6- Thiadiazines structure

Apart from the various tautomeric forms, there are four kinds of parent thiadiazine structures, having molecular formula C3H4N2S, in which the sulfur atom is adjacent to at least one ring nitrogen atom (structures I-IV). In order to name a particular tautomer, the extra hydrogen requires designation. Thus, using Chemical Abstracts nomenclature, structure I is named as 6//-1,2,3-thiadiazine, and structures V, VI and VII are named as... 

The electronic nature of the NSN fragment was studied, using both ab initio and DFT methods, for a series of 1,2,5-thiadiazoles and compared to the established zwitterionic structure of naphtha[l,8-rz/][l,2,6]thiadiazine 6 (Figure 1). 

The compilation of ring systems in Scheme 1 consists of all the ring systems discussed in this chapter. The first three lines of structures are fused oxadiazines, dithiazines, and thiadiazines, these ring systems are followed by various fused... 

Synthesis and structural studies of new 3-alkylamino-pyrido[43-e][l,2,4]thiadiazine 1,1-dioxides have been reported <99T5419>. 

No new structures of compounds belonging to this class have been determined using X-ray crystallography. Previously, the structures of triazolotetrazine 31, triazolothiadiazine 32, several bicyclic thiadiazines 33 (R = NH2, 0 K = H, Me X = NH, O, S), and the tetrasilinooxadisilole 34 have been reported and are discussed in CHEC-... 

The single crystal X-ray structure of 3-methyl-4//-pyrido[2,3- ] l>2,4-thiadiazine 1,1,-dioxide 13 was compared to that of diazoxide 14 in order to determine the predominant tautomeric form and it was found that both these thiadiazine-dioxides exist in the AH tautomeric form in the solid state <1995AXG2064>. 

Less useful preparations of 1,3,5-thiadiazines in which they are formed as components of mixtures include that of Chase and Walker.262 They isolated a thiadiazine as a product of the reaction of thiourea, bromine, and p-chlorophenylacetonitrile in acetone. The function of the nitrile, which was not incorporated into the product, is not apparent. The product of a similar reaction, without the nitrile, was assigned a dithiazine structure by Baumann.304 Oliver and Stokes202 also reported that a 1,3,5-thiadiazine is formed among the myriad of identified products of the 15-month air oxidation of l,l,5,5-tetramethyl-2,4-dithiobiuret. 

Other thiadiazine dioxides have been investigated (70CRV593). The 2//-tautomer (48) is favoured over the 4JT-tautomer (49) and structure (50) in which the tautomeric proton is on oxygen. The dihydro-1,2,6-thiadiazine dioxides are also thought to exist in the tautomeric equilibrium (51) i(52). 

H-1,2,4-thiadiazine, 4//-l,2,4-thiadiazine, and 2//-1,2,6-thiadiazine, respectively. If the sulfur atom exhibits a valency other than 2, then the valency is indicated by including the small Greek letter X after the numeral that specifies the ring sulfur atom, followed by a superscript numeral to indicate the valency of the sulfur atom. For instance, structure VIII is named 3//-1 A4,2,6-thiadiazine. The four thiadiazine systems can give rise to benzo-derivatives, i.e. structures IX-XII examples of all four types are known. 

X-ray diffraction studies on crystals of fluorenethiadazine 2 indicate a multiplanar structure for the 1,2,3-thiadiazine ring with the sulfur atom situated out of the general plane of the other ring atoms [81JCS(P1)2322],... 

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). 

Table 2 X-ray structure of bicyclic 1,2,6-thiadiazine-1,1-dioxide derivatives (25) and (26).

The structure of the pyrido[l,3,4]thiadiazine (13) was solved using x-ray crystallography during a reinvestigation of the reactions of dehydrodithizone (14). A detailed treatment of the data is presented <76JCS(Pl)i673>. 

The regio-orientation of the annelated 1,3,4-thiadiazine ring in 63 and 64 was established on the basis of the J(CH) values for the ring junction carbon resonances in the 13C-NMR spectra (86MI1). Structure 64 (R1 = CH3, R2 = COCH3) was further conclusively proved by X-ray crystallography (87KGS701). 

The nucleophilic substitution, amination, aldol-type condensation, oxidation, and hydrolysis of the l//-pyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxide system, structurally related to pteridine, were studied in detail <03HCA139>. Chlorinated pyrazines were directly oxidized to their corresponding iV-oxides using dimethyldioxirane in a completely regioselective fashion <03HEC221 >. 1,6-Dibenzoyl-5//, 10//-diimidazo[ 1,5-a 1, 5 -[Pg.374]

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. 

H. Tschesche, Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-l,3,4-thiadiazine scaffold,/. Med. Chem. 2001, 44, 3231-3243. 

The practical utility of the facile addition of mercaptoacetic acid across the double bond of an azomethine has been used in the synthesis of thiazolo-triazolothiadiazin-6(7//)-one (328). Thus, 7//-3-methyl-5-triazolo[3,4-f>]thiadiazine hydrochloride (327), obtained by reacting l-amino-2-methyl-j-triazolyl-2-thione (326) with chloroacetaldehyde di-ethylacetal, reacts with mercaptoacetic acid in the presence of p-toluenesulfonic acid in boiling anhydrous benzene for 40 hr using a Dean-Stark water separator followed by basification with sodium bicarbonate to furnish 8a//,9//-3-methylthiazolo[3,2-u]-[l,3,4]triazolo(3,4-f>](1,3,4]-thiadiazin-6(7//)-one (328) (74IJC287) (Scheme 77). The absorption at 1725 cm (lactam carbonyl) in product 328 supports the cyclic structure in preference to the open-chain acid structure. 

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