Synthesis of Substituted Phenothiazines Analogous to Methylene Blue by Electrophilic and Nucleophilic Aromatic Substitutions in Tandem. A Mechanistic Perspective.

S-2-Amino-5-(dimethylammonio)phenyl sulfothioate

“…For methylene blue dye, see: Bernthasen (1889); Zollinger (1991);Hunger (2003). For its preparation, see: Leventis et al (1997). For the synthesis of the title compound, see: Bogert & Updike (1927); Bennett & Bell (1943).…”

“…Phenothiazine dyes are class of colorants with application in various fields of which the methylene blue is the most well known (Zollinger, 1991;Hunger, 2003). Commercially, methylene blue is produced by oxidation of 4-N,N-dimethylaminoaniline with Na 2 Cr 2 O 7 in the presence of Na 2 S 2 O 3 , followed by the further oxidation in the presence of N,N-dimethylaniline, usually without isolation of intermediate 4-N,N-dimethylaminoaniline-2-tiosulfuric acid (Leventis et al, 1997). Namely, this compound was first described in 1889 (Bernthasen, 1889) and in the last hundred years reported by several authors.…”

Characterisation of 3,7-dibromophenothiazin-5-ium perbromide and its use for enhancing latent fingerprints

“…15 However, the authors of the later investigation characterised the salt 5 as a bromide rather than the original perbromide. 13,14,16 This is unusual because bromide readily reacts with bromine to give perbromide and excess bromine is present (20 equiv.). Dilute solutions of tetrabutylammonium bromide (TBAB) react completely with solutions of bromine as determined by UV spectrophotometry.…”

“…This verifies the position of the bromines since bromination can also occur in the 1 and 9 positions of phenothiazine. 16,[19][20] Both cyclohexene and sulfite were expected to reduce perbromide to bromide, but salt 5 also appears to be spontaneously reduced by these reagents. This result casts doubt on the claim by Kehrmann to have made phenothiazinium perbromide by brominating phenothiazine in acetic acid because only traces of phenothiazine were present after treatment of salt 5 with bisulfite or cyclohexene and Kehrmann's first paper reported the use of bisulfite in the work-up procedure.…”

“…3,7-Dibromophenothiazin-5-ium perbromide 5 has sometimes been mistaken for phenothiazinium perbromide 21,22 as well as their being confusion over the counterion. [15][16] The presence of unoxidised 3,7-dibromophenothiazine 9 in the salt 5, observed by TLC, suggests that the one minute reaction time may not be long enough for complete oxidation to occur, possibly due to HBr protonation of the amine, or that the salt slowly decomposes to this compound. The complete C 12 H 7 Br 2 NS molecule is generated by crystallographic mirror symmetry, with the N-H group and S atom lying on the reflecting plane.…”