1.4- Thiazines reactivity

There are oxazine disperse dyes reported (4) and several reactive dyes containing the oxazine ring and a few containing thiazine (5) (see Dyes, reactive). 

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]. 

Thiazine is not important in dyes as such, but it is a part of some reactive dyes (5). Thiazine is important in sulfur dyes (qv). 

Table 1. Effect of Substituents on the Redox Potential and Reactivity of Thiazine Leuco Dyes...

Phenazine leucos are generally more reactive and more susceptible to air oxidation than the thiazines and oxazines. Incorporation of electron-withdrawing groups on the acyl substituent at the 10-position of the leuco dye can provide a substantial improvement in the thermal and light stability of the leuco form and it is found that in general the stronger the electron-withdrawing character of the acyl substituents the more stable the leuco is.18... 

TVA -Disulfonylsulfodiimides 244 react exothermically with butadiene to give 1-sulfo-nylimino-2-sulfonyl-3,6-dihydro-l,2-thiazines 245 (equation 130)121,122. IV-Aryl-AT-sul-fonylsulfodiimides 246 are much less reactive as dienophiles. The addition to butadiene to yield 247 takes place in boiling benzene (equation 131)123. No cycloaddition reactions of dialkyl- or diarylsulfodiimides are known. 

A majority of the compounds encountered in this class of heterocycles exist as A -dioxides. The nomenclature for such compounds is somewhat ambiguous as the terms sultam, sulfonamide, and 1,2-thiazine 1,1-dioxide have all been used to describe these molecules. The reactivity of 1,2-thiazine 1,1-dioxides 4 (as the 22/-tautomer) has been thoroughly investigated and much of this work has been described in Chapter 6.06 of CHEG-II(1996) <1996CHEC-II(6)349>. This S(vi)-oxidized compound 4 undergoes both nucleophilic and electrophilic attack, which are often non-regioselective. 

Fully conjugated species are somewhat rare in the 1,2-thiazine class of heterocycles. These molecules are comprised of two separate subclasses, the first of which includes the highly reactive 1,2-thiazinylium salts. Although these salts, such as 27, have in some cases been isolated, they readily react regioselectively at C-6 with a variety of nucleophiles including sodium alkoxides 76, silyl enol ethers 77, sodium malonates 78, and sodium thiophenoxide 79 (Scheme 10) <2001T8965>. 

The 7-lactam 120, which is very reactive, is obtained from the reaction of methyl 2-(2-methoxycarbonylmethyl-ene)-5-methyl-3,6-dihydro-2//-l,3-thiazine-4-carboxylate 119 with oxalyl chloride and in the presence of triethyl-amine (Scheme 5). Subsequent treatment with methanol affords 3,6-dihydro-2//-l,3-thiazine 121 as a mixture of isomers. Similar treatment of the 4-allyl carboxylate analogue with oxalyl chloride/triethylamine yielded the corresponding 7-lactam <1999J(P1)2449>. 

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. 

Thiazines can be oxidized at the sulfur atom to give sulfoxides and eventually sulfones. Generally speaking, however, this is not a good approach to these structures as there are inherent problems of non-selectivity and over-oxidation. Air oxidation is sufficient to convert the 1,3-benzothiazine (24 R = alkoxy) into the 1-oxide (25 n = 1), whereas potassium permanganate yields the 1,1-dioxide (25 n = 2). In the case of the unsubstituted compound (24 R = H) the sulfur atom is less reactive and oxidation affords the l,3-benzothiazin-4-one (26) (77ACH(92)317). 

For less reactive thiazines sodium periodate or 3-chloroperbenzoic acid are suitable reagents for sulfoxide synthesis but it is not always possible to prevent over-oxidation and the formation of the corresponding sulfone (75JCS(P1)716>. Carbonyl substituents at C-6... 

The electrophilic properties of substituted 6//-l,3-thiazine-6-ones (208) in solution also shows reactivity at C-2 in acidic conditions and at C-6 in basic conditions. The regioselective reaction of 4-ethoxycarbonyl-2-phenyl-6//-l,3-thiazine-6-one with dimethylamine leads, after ring opening and reclosure, to two diasteriomeric 5-dimethylcarboxamido-4-ethoxy-carbonyl-2-phenyl-A2-thiazolines 209 and 210, whose structures were confirmed by X-ray diffraction studies on 210 (Scheme 84) (88BSF897). Com-... 

Oxazine, azine and thiazine dyes are named for the characteristic heterocyclic ring systems 1,4-oxazine, 1,4-diazine, and 1,4-thiazine. The dyes are generally cationic (basic) or acid dyes. They also can be reduced to colorless forms, then oxidized back to the dye, as in vat dyeing. The dyes also have been used to a limited extent in disperse and fiber reactive applications. They are used as titration indicators and may be applied to acrylic fibers and leather. 

Similarly, reaction of 3-chloroacylthio-3-isothiazoline-5-thiones (333) with reactive alkynic compounds proceeds with formation of the 1,3-dithiole derivatives (334) which contain thiazolone or 5,6-dihydro-l,3-thiazin-4-one rings (81H(16)595). 

The latter compound is similar to 60 (R = C02Et) in reactivity toward acenaphthylene, undergoing [4 + 2]-cycloaddition/cheleotropic elimination to the known sulhnylamine Et02C—N=S=0, which was sufficiently stable to be isolated but underwent facile cycloaddition with 2,3-dimethyl-1,3-butadiene to give the thiazine sulfoxide 65. Although 64 is a fairly reactive molecule, the reactivity in cycloaddition reactions is less than that of 60, which is in keeping with the known differences in reactivity of thiophene 1-oxide and thiophene 1,1-dioxide. 

In search for the key intermediates to meat flavor development in heated cysteine-sugar systems, it was found that in addition to thiazolidine derivatives also the tetrahydro-l,4-thiazine derivatives are being formed. These tetrahydro-l,4-thiazines, which are the cyclic form of Amadori compounds of cysteine, have excellent meat flavor precursor properties and are likely to play a prominent part in meat flavor development. Another major pathway to meat flavor development is the reaction of cysteine with the Amadori compounds of other amino acids. Model experiments showed that both pathways are probably of about equal importance for flavor development in boiled meat and process flavorings, this in spite of the low reactivity of cysteine with sugars. It seems that the first pathway is general-acid-catalyzed by the other amino acids, whereas the second pathway is inhibited by cysteine. 

Although an elusive compound because of its high reactivity, 1,4-benzo-thiazine has recently been prepared and shown to exist as the 2i/-tautomer... 

Although the subject of brief surveys, " the chemistry of mono-cyclic 1,4-thiazines has not previously been discussed in a comprehensive manner. The aim of this review is to consider the synthesis, reactivity, and physicochemical properties of these compounds and their dihydro derivatives. 

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