1.4- Thiazines structure

Further examples of fused-ring systems incorporating the 1,3-thiazine structure have been obtained by adaptations or extensions of conventional cyclization reactions they include the new tetrazolo[5,4-b][l,3]thiazinium ... 

As mentioned in the introduction, recent synthetic developments now allow access to the 1,2-thiazine structure via disconnection type C (Figure 23). This process can be accomplished by a Friedel-Crafts-type cyclization of sulfamoyl chlorides. The initial report of this reaction utilized a stoichometric amount of aluminium chloride promoter <19920PP463>. Recently, however, A -ethyl phenethylsulfamoyl chloride 214 was shown to undergo Friedel-Crafts cyclization to form sultam 215 with just a catalytic amount of In(OTf)3 (Equation 33) <2002SL1928>. 

Among the many other non-oxicam-type substances discovered are a sultam pro-drug for potential P3-lactam thrombin inhibitors <1998BML3683>. Furthermore, an anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) pharmacophore based on the 1,2-thiazine structure has also been recently disclosed <1999BML673>. Workers at Bristol-Meyers Squibb have synthesized and evaluated sultam hydroxamates as MMP-2 inhibitors <2004JME2981>. Hydroxamate 38 displayed the best selectivity for MMP-2 over the other proteins in this superfamily of peptidases (Figure 27). As noted in Section 8.07.3.1, an X-ray crystal structure of 38 bound to the protein MMP-13 protein has been solved. 

H- Pyrrolo[2,1 -c][l, 4]thiazine-7,8-dicarboxylic acid, 1 -hydroxy-4-methyl-synthesis, 6, 1003 Pyrrolothiazines synthesis, 4, 517 Pyrrolo[2, l-c][l, 4]thiazines structure, 6, 977... 

Thermolysis of 4//-l,3-thiazines (271) leads to thioamide vinylogues (272) by ring opening (Scheme 110) (86SC79). At more elevated temperature (toluene reflux), compound 273 is not isolated. A heterocyclic isomer (274) with a 3,4-dihydro-2//-l,3-thiazine structure is obtained (Scheme 111). 

The HPLC behavior of cyclic dipeptides with a dioxopyrazino[2,l-c][l,4]thiazine structure and of their sulfoxide analogues has been investigated <80CCC2927>. 

Racemization of cyclic dipeptides with pyrazino[l,2-c][l,3]thiazine and pyrazino[2,l-c][l,4]-thiazine structures has been studied <81TL3101>. 

Acetyl-2,3-dihydro-1,4-thiazine Structural class III 1766 N No safety concern... 

The results exclude possible alternative thiazine structures that have been considered from time to time. 

Several papers have been published on the synthesis and properties of fused-ring systems incorporating the 1,4-thiazine structure, mainly pyrido-[2,3-6]-l,4-thiazines, pyrazino[2,3-6]-1,4-thiazines, and pyrimido-[4,5-Z)]-l,4-thiazines, including some sulphur isosteres of dihydropteridines [e.g. (112)]. A detailed account of ring-chain tautomerism in 6-hydroxy-... 

The layout of the Chapter adopted in the previous Volumes of this Series is retained, except that further restrictions on space have precluded a fuller presentation of activity in some areas, e.g. fused-ring systems incorporating the thiazine structure. Moreover, the section dealing with simple 1,2-thiazines has been omitted, as no significant work in this field has recently appeared. 

But when the reaction is carried out in an aqueous solution of sodium hydrogen carbonate, extension of the ring occurs with formation of dihydro-l,4-thiazine derivative (Scheme 19). the structure of which has been established by mean of NMR and infrared spectra (41). 

Representatives of all three types of isomeric 1,3-oxazines 82-84 (X = O) and 1,3-thiazines 82-84 (X = S) and of the corresponding partially hydrogenated derivatives are known. However, no tautomeric interconversions between these structures have been observed. 

Chemical Name 2-(4-Chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide Common Name Chloromethazanone Structural Formula ... 

Conformational analysis using the Sybyl 6.8 program was performed on the proposed transition state structure of the pyrazino[2,l-A [l,3]thiazine 288 (R =Me, R2 = H, R3 = Arg-Trp-NH2) formed by solid-phase synthesis, to rationalize the stereochemical outcome of the ring formation <2004TL6333>. 

Single crystal X-ray analysis of the pyrimido[2,l-3][l,3]thiazine 293 was performed to verify the structure and the regioselectivity of the synthesis from diazadiene <2002S403>. 

The bis[l,2]-dithiolo[l,4]thiazines prepared by Rees and co-workers are nonplanar, with the thiazine ring 34° out of plane for the W-ethyl compound. This gives a scorpion-like conformation with the N-substituent as the scorpion tail, seen in the crystal structure of this and other analogues <1998JOC2189>. 

The bis[l,2]dithiolo[5,4- ][5, 4 -< ][l,4]thiazine ring systems of Rees and co-workers easily extrude sulfur from the thiazine ring and undergo contraction to the fused pyrrole derivatives <1997CC879>. These tricycles generally have a nonplanar, scorpion-like solid-state structure <1998JOC2189> however, the dicarbonyl product of... 

X-Ray elucidation provided a final proof for the structure elucidation of 8-(4-chlorophenyl)-8-hydroxy-5-methyl-8/f-[l,4]thiazino[3,4-H[l,2,4]oxadiazol-3-one 49, which was obtained as a product of ring-transformation reaction <1997J(P2)2407>. This analysis revealed that the oxadiazole ring is planar, whereas the thiazine ring is in a distorted half-chair conformation with a displacement asymmetry parameter AC2 (S—G(3)) = 0.031. The structure analysis represents the first X-ray elucidation of a [l,4]thiazine ring fused to a [l,2,4]triazole moiety. 

This is a pigment based on a thiazine indigo structure, of which no detailed composition has been disclosed. The orange pigment is recommended to be used for the coloration of paints and plastics, especially for the mass coloration of polyethylene. 

No pyrido[l,2-6][l,2]thiazine derivative has been the subject of theoretical or experimental structural studies. 

The reaction mode depends mainly on the choice of the base and reaction conditions, but route B is usually more common. Thus, tetrahydro-l,4-thiazine derivative 157 the structure of which was proved by X-ray crystal structure analysis (Fig. 7) [22b] was obtained in the reaction of the chloro ester 1-Me with 2-aminoethanethiol (156) using K2CO3 or EtgN as a base in 43 and 20% yield, respectively (Scheme 49) [22b, 26]. In the latter case, the secondary amino group in the primary tetrahydrothiazine product 157 underwent Michael addition to a second molecule of 1-Me to give 2-[r-(spirocyclopropanetetrahydrothiazinyl) cyclopropyl]-2-chloroacetate 158 (14% yield). When KOH in the presence of di-benzo-18-crown-6 was employed, however, the seven-membered heterocycles 155 (42%) and 159 (48%) were obtained upon reaction of 1-Me with 1,3-pro-panedithiol and 2-aminoethanethiol, respectively (Scheme 49) [26]. 

The reaction of thiourea with acetylenic esters has been variously reported to give a thiazolin-4-one (372), an imidazolinethione (373), or a l,3-thiazin-4-one (374) " derivative. However, recent studies have shown that in fact it is the thiazolin-4-one (372) that is formed in this reaction [Eq. (55)]. In the light of this observation, it may now be necessary to revise the structures of products obtained from the reaction of A -methylthiourea, M -dimethylthiourea, and thiosemicarbazides with acetylenic esters. The reaction of a thiourea derivative such as A(-thiocarbamoylpiperidine with DMAD is reported to give 5-(carbomethoxymethylene)-2-piperidino-A -1,3-thiazolin-4-one (375) [Eq. (56)]. °... 

The delocalised charged dyes are dominated by cyanine dyes, exemplified by the azacarbocyanine Cl Basic Yellow 11 (2.27), the diazacarbocyanine Cl Basic Yellow 28 (2.30) and the diazahemicyanine Cl Basic Blue 41 (2.49). Where necessary quatemisation is carried out as a post colour forming reaction. Other structural types include oxazines, thiazines and triphenyhnethane dyes. 

The fused benzo derivatives of 1,2-thiazines are of great commercial importance due to their potent biological activity (Figure 2). The three regioisomers of the benzothiazine A,A-dioxide structure are known 2,1-benzothiazine... 

The structure of A -sulfinyl compound 39 was solved using a single crystal grown by the slow evaporation of a solution of dichloromethane (DCM) and hexane (Figure 7) <2003T4651>. The A -sulfinyl compound crystallizes with two molecules in a unit cell. This work provides additional evidence for the (Z)-preference of this dienophile used in [4-1-2] cycloaddition reactions to prepare 1,2-thiazines. 

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