1,3-Thiazines basicity

Table 3.32 Migration properties of thiazine basic dyes on acrylic fibre [134]...

Thiazine basic dye. Biological stain. Used as 0.05% aq. soln. as indicator in iodometric titrimetry. Green cryst. (HCl aq.). Sol. H2O, EtOH, Mc2CO insol. CCI4. Mp 290° dec. Blue soln. in H2O A, 620-634 nm. 

Methylene Blue [61-73-4] CI Basic Blue 9 (CI 52015), (26), is the classic thiazine dye still in use today. This dye was first reported in 1876 (1). 

Dihydro-2/7- 74 and -4//-l,2-oxazines and thiazines 75 are interrelated by prototropy, being enamines and imines, respectively. In the case of oxazines, the imine form 75 is favored, and there are several well established examples of this system, including the parent heterocycle 75 (X = O) [84MI2]. No tautomeric equilibrium between the 2H and 4H forms has been observed under normal conditions in solution or in the solid state. However, the formation of intermediate 2H isomers 77 was proposed both for the conversion of 3-phenyl-5,6-dihydro-4//-l,2-oxazine 76 (R = Ph, r = R = H) into 2-phenylpyrrole(89TL3471) under strong basic conditions and for thermal decomposition of cyclopentene-fused 1,2-oxazine 76... 

Basic hydrolysis of the [l,2,4]triazolo[5,l-3][l,3]thiazine derivative 77 was described to yield triazole-thione 78, the reaction proceeding in 59% yield <2005ZOR1092>. Related partially saturated triazolothiazines 79 were also subjected to ring-opening reaction aqueous hydrolysis afforded the acid 80 <2004KGS1256>, whereas reaction of 79 with hydrazine hydrate yielded the acid hydrazine 81 <2004ZOR260>. Both transformations took place in high yields. 

Ethoxy-4//-l,3-thiazines bearing an NMe2 substituent at carbon 4 are reducible in two 2-e steps in slightly basic media. An electroreduction performed at the first wave is followed by a dimethylamine elimination (Scheme 143) [259, 260]. The electrolysis carried out at the second... 

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 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 spiro compound 15 is obtained in excellent yield by the cycloaddition of 3-(4-fluorophenylimino)indolin-2-one with mercaptopropionic acid under microwave irradiation <2003SUL201>. Treatment under basic conditions of 2,3-dihalopropylamines with carbon disulfide results in the formation of two isomeric products 5-halotetrahydro-l,3-thiazine-2-thione 204 and 5-(halomethyl)thiazolidine-2-thione 205 <2002CHE1533>. 

Perfluoro(3-isothiocyanato-2-methyl-2-pentene) reacts with N-nucleophiles to produce a series of fluoroalkyl-substituted 6/f-l,3-thiazines <1997RJO720>. The acid-catalyzed cyclization of thioureas immobilized on Wang (X = O) or Rink resin (X = NH) provides a convenient route to a wide range of 2-amino-4/7-benzothiazine derivatives 212 (Scheme 23) <20000L3667>. The thioureas are obtained in four steps from 2-nitrocinnamic acids. A general synthesis of 2-alkylidene-4-imino-l,4-dihydrobenzo-l,3-thiazines 213-215 involves treatment of 2-isothiocyanato-benzonitrile with acidic methylene compounds under basic conditions <2003SL1503>. The ( )-isomers are the predominant isomers formed. 

Thiazin-4-ones 236 are obtained when 2-chloro-2-(T(Timinomethylthio)cyclopropyl)acetates 235 are reacted with titanium tetraisopropoxide in dichloromethane <2001EJ03025>. The yield is dependent on the group attached to C-2 and observed diastereoselectivities are poor. Representative examples are shown in (Scheme 29). Interestingly, thiazolines 237 are formed under basic conditions. 

A six-membered nitrogen-sulfur heterocycle, namely, a 2,3-dihydro-2-imino-4//-benzo[e thiazin-4-one, is produced on reaction of methyl 2-chloro-3,5-dinitrobenzoatc with thiourea in basic medium 373 furthermore, a tetrahydrospirobenzothiazine 213 is formed in addition to its hexahydrospiroquinazoline analog on interaction of cyclohexanone with thiourea in hydrochloric acid.329... 

Treatment of 3,6-dihydroxy-3,4-dihydro-2//-pyrido[2,l-h][l,3] thiazinium salt (86) with orthophosphoric acid at 140°C for 34 h or with cone, sulfuric acid at ambient temperature for 5 h afforded 1 1 and 3 1 mixtures of pyrido[2,l-6][l,3]thiazine (87) and thiazolo[3,2-a]pyridine (88), respectively (70ACS2949). Under basic conditions, only extensive destruction of 86 was observed. When 3-hydroxy-2,3,4,6-tetrahydro[l,3]thiazino[2,3-a]isoquinolin-6-one was left to stand in cone, sulfuric acid at room temperature overnight, 4,6-dihydro[l,3]thiazino[2,3-a]isoquinolin-6-one was obtained in 61% yield (72ACS1620). 9-Oxido-3,4-dihydro-2H-pyrido[2,l-h] [l,3]thiazinium betaine did not undergo cycloaddition even under extreme conditions [81JCR(S)208],... 

These and other venerable synthetic routes to the tricyclic oxazines and thiazines have been reviewed in detail (B-78MI22701). 2-Hydroxy(or mercapto)-2, 4 -dinitrodiphenylamines readily cyclize to phenoxazines (or phenothiazines) in basic media through elimination of nitrous acid. This is the so-called Turpin reaction, which is complicated by the fact that the intermediate Meisenheimer complexes (251) may undergo a Smiles-type rearrangement so that mixtures of isomeric products are obtained (Scheme 112). 

The basicities of the few 1,3-thiazines studied are located between those of sodium bicarbonate and ammonia. Ethyl 2-methylamino-l,3-thiazine-5 carboxylate (72) has pKa 5.41 (65JOC2290). Russian authors have determined the basicities of some compounds by potentiometric titration with perchloric acid in ethanol. The 2-methyliminothiazine (119), pKa 7.84, is more basic than the isomeric aminothiazine (120), pKa 7.12 (71KGS946). 

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-... 

Reaction of 4-benzylidene-l-phenylpyrrolidine-2,3,5-trione 56 with thiourea 28 occurs with hydrolysis of the amino group and leads to the formation ofl,4-dihydropyrrolo[3,4-J][l,3]thiazine-2,5,7-trione 57 [65] (Scheme 3.17). There is just one reference to the formation of a dihydrothiazine derivative 59 in the reaction of thiourea with an unsaturated ketone 58 under basic catalysis [68] (Scheme 3.18). 

Basic (cationic) dyes contain cationic groups which are ionized in the dyebath. They are applied to acrylics, nylon, polyester, and paper and are most often azo, anthraquinone, triarylmethane, quinoline, thiazine, methine, oxazine, and acridine types. 

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. 

Cationic (Basic) Dyes. These water-soluble cationic dyes are applied to paper, polyacrylonitrile (e g. Dralon), modified nylons, and modified polyesters. Their original use was for silk, wool, and tannin-mordanted cotton when brightness of shade was more important than fastness to light and washing. Basic dyes are water-soluble and yield colored cations in solution. For this reason they are frequently referred to as cationic dyes. The principal chemical classes are diazahemi-cyanine, triarylmethane, cyanine, hemicyanine, thiazine, oxazine, and acridine. Some basic dyes show biological activity and are used in medicine as antiseptics. 

Attempts to acylate 2-unsubstituted thiazolylium salts with dialkylacylphosphonates under basic conditions yield an intermediate (72) which rearranges with ring expansion affording a 1,4-thiazine (73 Scheme 38). Under the same reaction conditions, 2-unsubstituted benzothiazolylium salts give 1,4-benzothiazines of type (74 Scheme 39). 

Most of the older antidepressants are called tricyclic because their chemical nucleus has the basic tricyclic structure of the original pheno-thiazine neuroleptic, chlorpromazine, or Thorazine (Bassuk et ah, 1977 Pauker, 1981). Of extreme importance, the antidepressant amoxapine (Asendin) is turned into a neuroleptic in the body, producing the same problems as any other neuroleptic, including tardive dyskinesia (chapters 3 and 4). 

Marquis Test (p. 139). Many basic drugs produce colours with diis reagent. It is a good test for opiates, stimulants, antihistamines, and pheno-thiazines. 

Disproportionation equilibria have been studied for various systems. Cauquis and co-workers investigated by electrochemical means the matrix of equilibria corresponding to Scheme 2 for 3,7-dimethoxypheno-thiazine and its derivatives, and applied the measurement of the response of the equilibria to different conditions of basicity to the definition of a scale of basicity in acetonitrile. The disproportionation kinetics of the iron-thionine system were measured several years ago solvent effects on the disproportionation rate constant have been examined, and, lately, an indirect measurement of the synproportionation rate constant of thionine and leucothionine has been made. ... 

Basic Cationic azo, acridine, anthraquinone, oxazine, thiazine, triarylmethane, and xanthene. 

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