Thiazine Ring

Modifications in the Thiazine Ring.— The allylic position at C-2 in the 3-cephem sulphoxides (51) is quite reactive, and under Mannich conditions (formaldehyde, secondary amine salts) gave the exo-methylene-3-cephem (52 b, w) presumably, loss of the amino-function occurred under the reaction conditions. Both hydrogenation and addition of thiols 

Modification at C-3 of the thiazine ring is an area which has been extensively exploited, and an excellent review of the pre-1972 literature has 

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Very little is known about the chemistry of later steps of in vitro phaeomelanogenesis beyond the benzothiazine stage. Radiotracer studies (160) and model experiments (161) suggest that the alanyl side chain of the postulated intermediates does not take part in the polymerization process, which probably proceeds via an enamine-imine type condensation of the 1,4-thiazine ring system rather than by oxidative coupling at positions 2 and 8 and subsequent ring closure of the alanyl side chain as previously suggested by Minale et al. (162,163). 

It is now more than 30 years since the first monocyclic 1,4-thiazine was described nevertheless, the chemistry of such compounds is still relatively undeveloped. The 1,4-thiazine ring is of importance in nature where, in fusion with the benzene ring, it is found in the trichochrome pigments. It is also a structural feature of the phenothiazines, synthetic compounds that are of considerable medicinal value. Furthermore, 1,4-thiazines are of in-... 

Heterocyclics from carbohydrates Ring closure with sulfonic acid esters Dihydro-1,4-thiazine ring... 

There are also examples of reactive dyes having only oxazine heterocycHc rings in the chromophore such as (15) [58104-86-2] as well as those having both oxazine and thiazine rings such as (16) [97140-65-3]. 

The parent 1,4-thiazine exists exclusively as the 2H tautomer 86, independently of the medium used, as do its pyrimidino-fused derivatives 87 (76AHCS1, p. 80 84MI2). However, the equilibrium could be affected significantly by a substitution pattern in the thiazine ring, as was shown in the example of 1,4-benzothiazine. Thus, 3-phenyl-1,4-benzothiazine 88 (R = H, R = Ph) is present in aqueous hydrochloric acid as a 4 1 mixture of 2H (88a) and AH (88b) isomers... 

Bei Reduktion mit Natriumboranat in alkalischem Milieu wird der 5,6-Dihydro-4H-1,3-thiazin-Ring aufgespalten4. 

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... 

Rees and co-workers have carried out extensive studies of the highly sulfurated bis[l,2]-dithiolo[l,4]thiazine ring system 469, formed by reaction of Hiinig s base 468 with S2C12 and l,4-diazabicyclo[2.2.2]octane (DABCO) (Equation 128) <1997AGE281>. 

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. 

Several new cyclizations to [l,2,4]triazolo[3,4-A [l,3]thiazines have been published recently, and these are summarized in Scheme 40. In all the four cases shown here, the thiazine ring is partially saturated. 

Moreover, there are several patents and reports on cephalosporins and 7-alkoxy derivatives thereof, which are characterized by a pyridazine-derived substituent attached to the thiazine ring. Some typical examples are given in formulae (126) [347-356], (127) [357], (128) [358], (129) [359, 360] and (130) [355, 361-363] in which R1 represents a variable acyl group. 

Fully conjugated thiazine 46 has only one hydrogen (C-8) in the 1,2-thiazine ring which is observed at 8.59 ppm, while the resonance of the attached carbon atom occurs at 141.4 ppm in the NMR spectrum (Figure 13) <2005JOC9314>. 

The H and NMR spectra of 1,2-dihydrobenzothiazine 47 were obtained and the only 1,2-thiazine ring hydrogen resonance was observed at 3.17 ppm (Figure 14) <2000JOC8152>. 

The azulenes 68 and 69 displayed a reversible reduction wave at —1.48 V for 68 and —1.42 V for 69, which have been attributed to the delocalization of the radical anion between the azulene and 1,2-thiazine ring systems (Scheme 9) <2003T4651>. 

An N-debenzylation reaction with concomitant hydrogenation of a double bond in the thiazine ring was observed with 1,2-thiazine nitrogen 107 (see Equation 12) <1994TL2911>. 

In this context, conjugated ring systems refers to 1,3-thiazine rings which do not contain an sp -hybridized carbon or nitrogen. There has been little activity in this area and developments are limited to the reaction of 6//-l,3-thiazin-6-iminium salts. 

When the 5-phenyltetrahydro-l,3-thiazine-2,4-dione 155 is treated with NaBH4, the thiazine ring fragments to produce (3 )-3-mercapto-3-phenylpropan-l-ol in 45% yield and the oxazolidin-2-ones 156 and 157 as a mixture of diastereomers (Equation 11) <2006TL1153>. 

Figure 1 The fully conjugated thiazine ring systems covered in this chapter.

Figure 2 The nonconjugated thiazine ring systems that appear in this chapter.

Phenothiazine derivatives and compounds with two or three thiazine rings conjugated to each other, such as 98 and 99 <2004JA1388>, 159, 160, and 161 <2003EJO3534>, have interesting electronic properties (see also Section 12.2) and their cyclic voltammetry has been studied. These compounds are oxidized stepwise until each phenothiazine moiety has lost an electron. 

A nucleophilic attack of an N-tethered phenethyl substituent is shown in Scheme 50. The protonated thiazine ring brings about an intramolecular electrophilic aromatic substitution on the aryl substituent, whether this is a phenyl <1992CHE832> or a veratryl ring <1980JHC449>. 

Thus, the presence of a thiamine ring in Cl Sulfur Blue 9 was conclusively proved. The thiazine ring is the fundamental chromophore that accounts for the high color value of both the sulfur dye and Methylene Blue [61-73 1-], including their ability to form pale yellow leuco forms on reduction. Methylene Violet (IS) is obtained from Methylene Blue (16) by hydrolysis in boiling alkali... 

On more severe thionation, a third thiazine ring is formed to give a sulfur black. However, if hydroxyl groups instead of amino groups are attached at positions 2 and 2, no ring closure would take place and the blue dye would be stable to heat. These formulas are general expressions for the nuclear structures of the blue-to-black sulfur dyes they do not take into consideration the quinonoid formation of each dye and other aspects. 

Immedial Pure Blue (25) forms a crystalline complex with sodium bisulfite and the thiazine ring structure has been clearly established (48AG141). The compound is isosteric with a number of vat dyes, e.g. indanthrone, and thus its hue and good affinity for cellulosic fibres might reasonably be expected. 

The 1,3-thiazine ring system may be prepared by treating various... 

A preparation of the thiazine ring system which should be investigated for generality is that of Baranova et al.,2il who interacted the l-aroyl-2-thioureas 151 with carbon suboxide to give 152. Compounds of structure similar to 152 were also obtained starting with 1,1-disub-stituted thioureas.247 Treatment of other cumulenes 153, ketenes(X = O)... 

A sulfone group incorporated within a l,l-dioxo-l,4-thiazine ring is also present in 6-(p-hydroxyphenyl)-2i/-3,4-dihydro-l,l-dioxo-l,4-thiazine (286), a compound obtained from the sponge Anchinoe tenacior [211], and in euthyroideones A-C (287-289), which are brominated quinone methides isolated from the New Zealand bryozoan Euthyroides episcopalis (order Cheilostomatida, suborder Ascophotina, family Euthyroididae) [212]. The spectral data of euthyroideone A (287), secured by X-ray analysis, was used for the structural determination of euthyroideones B (288) and C (289). Compound 288 showed a weak cytotoxic activity towards the BSC-1 cell line. 

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