Phenothiazines, synthesis

Phenothiazines, synthesis, properties, analytical applications of 83WCH231. 

Pechmann reaction, 3, 802 Phenolsulfonephthaleins dyes, 6, 782 Phenosafranine applications, 3, 196 Phenothiazine, 3,7-dichloro-synthesis, 3, 1012 Phenothiazine, 5-ethyl-carbazoles from, 4, 152-153 Phenothiazine, 1-methyl-synthesis, 3, 1033 Phenothiazine, 10-phenyl-synthesis, 3, 1012 Phenothiazine, 10-sulfonyl-rearrangement, 3, 1012 Phenothiazines... 

Aromatic denitrocyclizations have been used for many years in some well-known synthetic reactions. Probably the best known example is the Turpin synthesis of phenoxazines and similar synthesis of phenothiazines. The classical setup used usually base-catalyzed reactions in polar protic solvents, very often alcohols. In many cases using polar aprotic solvents was found advantageous. Besides the mentioned influence of the H-bonding, better ionization and lower solvation of the nucleophile are also important. Sf Ar reactions proceed through strongly polarized complexes, which are well soluble and highly polarized in polar aprotic solvents. 

Formation of 1,3-dinitro- and 1,3,6-trinitroselenazine derivatives by a method analogous to the synthesis of phenothiazines have been also described (14CB1873). 

Phenols, pAfa values of 586-589 Phenothiazine oxides, mass spectra of 130 2-Phenylsulphinyl-l-indanols, synthesis of 256... 

Phenothiazines are well-known as intermediates for pharmaceuticals, and are also active as insecticides and antioxidants. These compounds are usually prepared by the thiation of diphenylamines with elemental sulfur. In this context, the group of Toma has elaborated a synthesis of 3-phthalimidophenothiazine, as shown in Scheme 6.265 [455]. Using a variety of high-boiling solvents under conventional thermal reflux conditions, low isolated yields of the desired product were obtained. The highest conversion and isolated product yield (55%) was achieved by microwave irradiation of a mixture of the starting N-(4-phenylaminophenyl)phthalimide with... 

X. Kong, A.P. Kulkarni, and S.A. Jenekhe, Phenothiazine-based conjugated polymers synthesis, electrochemistry, and light-emitting properties, Macromolecules, 36 8992-8999, 2003. 

For some reviews, see (a) Majoral J-P (2007) Influence of cationic phosphorus dendrimers on the surfactant-induced synthesis of mesostructured nanoporous silica. New J Chem 31 1259-1263 (b) Puntoriero F, Nastasi F, Cavazzini M et al (2007) Coupling synthetic antenna and electron donor species a tetranuclear mixed-metal Os(II)-Ru(II) dendrimer containing six phenothiazine donor subunits at the periphery. Coord Chem Rev... 

Synthesis of chlorpromazine, a very sedating phenothiazine antihistamine. ... 

An alternative synthesis of 4-nitrodibenzothiophene involves heating 2-amino-2 -nitrodiphenyl sulfide in a sealed tube at 190° (20%). The reaction probably proceeds via homolytic cleavage of the derived diazonium ion which could have been formed from nitrous acid liberated during the formation of phenothiazines, which were also detected. Similarly, 2-methyl-4-nitrodibenzothiophene is formed from 2-amino-2 -nitro-4 -methyldiphenyl sulfide (10%), and in this case the intermediacy of the diazonium ion was further indicated in that the same material was obtained by pyrolysis of the separately prepared diazonium salt of the sulfide. Although yields are poor in this reaction, it nevertheless represents the only route to substituted dibenzothiophenes containing a nitro substituent in the 4-position and as such is worthy of further attention. 

Synthesis of a new dipyrido-l,4-thiazine 328 has been described involving a Smiles rearrangement, and A -alkylation, arylation and heteroarylation of 328 have been repotted as well as its promising anti-tumor activity <2007H(71)1347>. Phenothiazine derivatives such as 329 and 330 have been developed for use in dye-sensitized solar cells <2007CC3741>. 

TABLE 11. Synthesis of phenothiazine having a fully substituted enamine structure (181)... 

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

The preparation of a diarylamine required for the synthesis of a phenothiazine via the sulfuration reaction requires the use of an activated chlorobenzene. 

Skraup quinoline synthesis, 443 Smiles rearrangement, phenothiazine, 534 Spiroalkylation, 222, 280 Spirocyclization, conjugate addition, 386 Spiroimidazolone formation, 335 Spiropyrazolopiperidine, 375 Stannylation, alkyne, 15 Stereoselective dehydration, 198 Grignard addition, 198, 199 reduction, 129, 226 hydroxyketone, 400 iminoketone beta, 553 oxazaborohydride, 585 transfer chirality, 321 Stilbene formation, self alkylation, 525 Stobbe condensation, benzophenone, 103... 

An attempt to alkylate phenothiazine with propargyl bromide using sodium hydride in dimethylformamide afforded a 70% yield of N-( 1 -propynyl)pheno-thiazine instead of the expected JV-(2-propynyl)phenothiazine [7], This reaction (Eq. 33) constituted the first synthesis of an ynamine [7]. Other diaryl-... 

The addition of alkylated phenothiazines, e.g., decylphenothiaz-ine or tetradecylphenothiazine still improves the performance (67). Alkylated phenothiazines are synthesized by the reaction of an alkylated diphenylamine with elementary sulfur. The synthesis is shown in Figure 6.9. 

Prochlorperazine Maleate. 2-Chloro-10-[3-(4-methyl-l-piperazinyl)-propyl]-10 H-phenothiazine maleate [84-02-6] (Compazine) (22) is a white or pale yellow crystalline powder. It is almost completely odorless, its saturated solution is acidic to litmus, it is practically insoluble in water and ethanol, and it is slightly soluble in warm chloroform. It may be made by the synthesis described in Reference 18. Prochlorperazine maleate [84-02-6] is an effective antiemetic and tranquilizing agent. It is not particularly effective for motion sickness. Adverse reactions that may occur include extrapyramidal reactions, motor resdessness, dystonias, tardive dyskinesia, and contact dermatitis. Prochlorperazine is also a significant phenothiazine antipsychotic. 

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