Thiazines reduction

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

Benzofuro[3,2-c]pyrroles reduction, 4, 1079 Benzofuro[3,2-6]pyrylium salts synthesis, 4, 995 Benzofuro[2,3-c][l, 2]thiazine... 

The thiazine dyes used in the preparation of this type of leuco are obtained through oxidative coupling of phenothiazine with an active methylene compound or an aniline. The reduction of the dye 23 with zinc powder in acetic acid is straightforward.9 Treatment of the leuco 24 with acetic anhydride at 40°C yields a more air stable leuco 25.9 Addition of arylsulfinic acid to thiazine dyes such as 26 produces directly leuco dyes such as 27.Sb... 

As in the case of thiazine and oxazine leuco dyes described earlier, the reductive acylation of the phenazine dye 52 results in the acylation of the exocyclic amino group.18 The phenazine leuco obtained 53 retains the exocyclic amide group on oxidation resulting in the acylated phenazine dye 54, the color of which is different from the one intended. 

The exocyclic double bond of (tetrahydro-l,3-thiazin-2-ylidene)malo-nate (527) was saturated by reduction with Hg/Al in methanol at ambient... 

When the cathodic reduction of 2-phenyl-6//-l,3-thiazines monoactivated at the C-5 position is carried out at the foot of the first wave, hydrodimers resulting from coupling at the C-2 position were obtained in relatively good yields (Scheme 158) [255, 256]. 

AN—N bond cleavage can be obtained by tion of 4-//-l,3-thiazine derivatives in a the cathodic reduction of some mesoionic slightly basic medium leads to a ring... 

The reaction of 1,4-diphenylbuta-l,3-diene (2) with trithiazyl trichloride (3) yields a bi(thiadiazole) (4), an isothiazoloisothiazole (5), a dithiazolothiazine (6), and two thiazin-odithiatriazepines (7) and (8) by 1,2-, 1,3-, and 1,4-cycloaddition reactions (Scheme 2). The bridged-mode (/3-tether) tandem inter-[4 -E 2]/intra-[3 -E 2] cycloaddition of (ii)-2-methyl-2-nitrostyrene (9) with 1-butoxypenta-1,4-diene (10) produces stable tricyclic nitroso acetals (11) which afford, after reduction and protection, highly functionalized aminocyclopentanedimethanol triacetates (12) (Scheme 3). ... 

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>. 

Reduction of A -sulfonimine 102 with LAH affords a 60 40 mixture of transxis reduced bicyclic perhydro-l,2-thiazines 103 and 104 in 85% combined yield (Equation 10) <1998CJC164>. In contrast, the NaBH4 reduction of bridged bicycle 105 affords compound 106 as a single diastereomer (Equation 11) <2002HCA1973>. 

A facile synthesis of 2,4-disubstitued-tetrahydro-l,3-thiazines 40 involves reduction of the 5,6-dihydro-4//-l,3-thiazine 130 with NaBH3CN to give the ty -isomers (Equation 5) <2004TL1503>. 

The carbon-sulfur bond of thiazines can be reductively cleaved (Sections 7.06.5.7 and 7.06.6.7) and 2//-thiazines, being imines, can be hydrolyzed (Section 7.06.5.5). Saturated thiazines (thiomorpholines) are stable toward alkaline hydrolysis <1981CPB1554> and Lewis-acidic boron trifluoride <1980JHC449>. 

Catalytic hydrogenation of 1,4-thiazines is shown in Scheme 18. Both partial and complete hydrogenation of 54 has been performed successfully <1992JA4307>, but 2/7-1,4-thiazines 108, 198, and 199 underwent reductive cleavage of the C-S bond followed by cyclization to form a five-membered ring under similar conditions <1968G488>. 

In the only report of the generation of a pyridazino[3,4- ][l,4]thiazine <1992JHC1409>, reduction of a 2-(3-nitropyridazin-4-yl)thioacetic acid derivative is accompanied by cyclization (Equation 164). 

Reactivity of pyrazino[2,3-3][l,3]thiazines was described in CHEC-II(1996) <1996CHEC-II(7)737>. The only recent report of reactions of this system, as summarized in Scheme 99 <2004CPB675>, describes N-protection followed by an ester reduction/homologation sequence. After further elaboration of the side chain, the ring nitrogen is deprotected by treatment with hydrochloric acid. 

The acetamido alkenethiolate (416), generated by the reductive cleavage of 2,3-dihydro-l,4-thiazin-2-one (415) in liquid ammonia (cf. p. 625), reacted with l-chloro-3-bromopropane in a two-stage process to give (417). 

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... 

Many complex dye molecules form triplet states which undergo facile reduction. Thiazine dyes such as thionine, 49, and methylene blue are photoreduced by a variety of oxidizing agents, including ferrous ion.475... 

Reduction of the parent systems is of little importance as reduced forms of 1,4-oxazines and -thiazines are readily available by other means moreover, hydrogenation of thiazines may effect cleavage and ring contraction to thiazolines rather than straightforward addition to a double bond as was once supposed (Scheme 39) (68G17). 

The reduction of dihydro-1,4-thiazines to tetrahydro forms is achieved by the action of a variety of reagents including formic acid, hydrogen sulfide, sodium borohydride and lithium aluminum hydride. The last is particularly useful for the reduction of carbonyl derivatives, although in the case of the amide (105) only partial reduction is effected, leading in due course to the thiazine (106), the hydroxyethyl side chain of which then cyclizes to position 5 of the ring to yield the bicyclic product (107 Scheme 45) (66CPB742). 

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