Phenothiazine

Phenothiazine
IUPAC name 10H-phenothiazine
Other names thiodiphenylamine, dibenzothiazine, dibenzoparathiazine, 10H-dibenzo-[b,e]-1,4-thiazine, PTZ
Identifiers
CAS number	92-84-2 Y
ChemSpider	21106365 Y
UNII	GS9EX7QNU6 Y
KEGG	D02601 Y
ChEBI	CHEBI:37931 N
ChEMBL	CHEMBL828 Y
Jmol-3D images	Image 1
SMILES c1ccc2c(c1)Nc3ccccc3S2
InChI InChI=1S/C12H9NS/c1-3-7-11-9(5-1)13-10-6-2-4-8-12(10)14-11/h1-8,13H Y Key: WJFKNYWRSNBZNX-UHFFFAOYSA-N Y InChI=1/C12H9NS/c1-3-7-11-9(5-1)13-10-6-2-4-8-12(10)14-11/h1-8,13H Key: WJFKNYWRSNBZNX-UHFFFAOYAI
Properties
Molecular formula	C12H9NS
Molar mass	199.27 g/mol
Appearance	yellow rhombic leaflets or diamond-shaped plates
Melting point	185 °C, 458 K, 365 °F
Boiling point	371 °C, 644 K, 700 °F
Solubility in water	0.00051 g/L (20 °C)[1]
Solubility in other solvents	benzene, ether, petroleum ether, chloroform, hot acetic acid, ethanol (slightly), mineral oil (slightly)
Acidity (pKa)	approx 23 in DMSO
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S(C₆H₄)₂NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds. Derivatives of the parent compound find wide use as drugs.

Synthesis

The compound was originally prepared by Bernthsen in 1883 via the reaction of diphenylamine with sulfur, but more recent syntheses rely on the cyclization of 2-substituted diphenylsulfide. The pharmaceutically significant derivatives of phenothiazine are not prepared from phenothiazine.^[2]

Non-drug applications

The synthetic dye methylene blue, containing the structure, was described in 1876. Phenothiazine itself was introduced by DuPont as an insecticide in 1935.^[3] It is sometimes used as an antihelminthic in livestock.

In the manufacture of monomers, Phenothiazine is used as a chemical stabilizer or inhibitor to prolong storage and shelf life of products like acryloyl chloride.^[4]

Many water soluble phenothiazine derivatives such as methylene blue, methylene green, thionine, and others are able to be electropolymerized into conductive polymers that are used as electrocatalysts for NADH oxidation in enzymatic biosensors and biofuel cells. ^[5],^[6],^[7]

Phenothiazine-derived drugs

The phenothiazine structure occurs in various neuroleptic drugs, e.g. chlorpromazine, and antihistaminic drugs, e.g. promethazine. The term "phenothiazines" describes the largest of the five main classes of neuroleptic antipsychotic drugs. These drugs have antipsychotic and, often, antiemetic properties, although they may also cause severe side effects such as extrapyramidal symptoms (including akathisia and tardive dyskinesia), hyperprolactinaemia, and the rare but potentially fatal neuroleptic malignant syndrome as well as substantial weight gain.

Phenothiazines are used as inodilators in congestive heart failure, acting upon the type I calcium/calmodulin dependent phosphodiesterase.^{[8][citation needed]}

Phenothiazine antipsychotics are classified into three groups that differ with respect to the substituent on nitrogen: the aliphatic compounds (bearing acyclic groups), the "piperidines" (bearing piperidine-derived groups), and the piperazine (bearing piperazine-derived substituents).

Group	Autonomic	Example	Sedative	Extrapyramidal side-effect
Aliphatic compounds
	moderate	Chlorpromazine (marketed as Thorazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil)	strong	moderate
		Promazine (trade name Sparine)	moderate	moderate
		Triflupromazine (trade names Stelazine, Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin)	strong	moderate/strong
		Levomepromazine in Germany and Methotrimeprazine in America (trade names Nozinan, Levoprome)	extremely strong	low
Piperidines	strong	Mesoridazine (trade name Serentil)	strong	weak
		Thioridazine (trade names Mellaril, Novoridazine, Thioril)	strong	weak
Piperazines	weak	Fluphenazine (trade names Prolixin, Permitil, Modecate, Moditen)	weak/moderate	strong
		Perphenazine (sold as Trilafon, Etrafon, Triavil, Phenazine)	weak/moderate	strong
		Prochlorperazine (trade names Compazine, Stemetil)
		Trifluoperazine (trade name Stelazine)	moderate	strong

Appendix: tradenames for phenothiazine

Like many commercially significant compounds, phenothiazine has numerous trade names including AFI-Tiazin; Agrazine; Antiverm; Biverm; Dibenzothiazine; Orimon; Lethelmin; Souframine; Nemazene; Vermitin; Padophene; Fenoverm; Fentiazine; Contaverm; Fenothiazine; Phenovarm; Ieeno; ENT 38; Helmetina; Helmetine, Penthazine; XL-50; Wurm-thional; Phenegic; Phenovis; Phenoxur; Reconox.^[9]

References

1. ^ Sigma-Aldrich catalog
2. ^ Gérard Taurand, "Phenothiazine and Derivatives" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.doi:10.1002/14356007.a19_387
3. ^ History of Insecticides and Control Equipment Clemson University Pesticide Information Program.
4. ^ PTZ Technical Information Bulletin Cytec PTZ Technical Information Bulletin
5. ^ http://www.sciencedirect.com/science/article/pii/000326709485016X
6. ^ http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291521-4109%28199906%2911:8%3C553::AID-ELAN553%3E3.0.CO;2-6/abstract
7. ^ http://www.sciencedirect.com/science/article/pii/S0956566308003916
8. ^ Rang; Dale et al., Pharmacology, 6th edition
9. ^ U.S. Department of Labor Occupational Safety & Health Administration Chemical Sampling Information Phenothiazine Also see: OSHA Also see:PAN Pesticides Database

Further reading

• MSDS
• Hendricks, Christensen, J.B., and Kristiansen, Jette E. Sonderborg, Denmark. "Antibakterielle Eigenschaften der Phenothiazine: Eine Behandlungsoption für die Zukunft?" Chemotherapie Journal. 13.5. (2004): 203–205. Wissenschaftliche Verlagsgesesellschaft mbH. 21 August 2005. (PDF).
• PubChem Substance Summary: Phenothiazine National Center for Biotechnology Information.