Phenothiazine

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Phenothiazine
Phenothiazin.svg
Phenothiazine-McDowell-3D-vdW.png
Phenothiazine-non-planar-McDowell-3D-balls.png
Identifiers
CAS number92-84-2 YesY
ChemSpider21106365 YesY
UNIIGS9EX7QNU6 YesY
KEGGD02601 YesY
ChEBICHEBI:37931 N
ChEMBLCHEMBL828 YesY
Jmol-3D imagesImage 1
Properties
Molecular formulaC12H9NS
Molar mass199.27 g/mol
Appearanceyellow rhombic leaflets or

diamond-shaped plates

Melting point185 °C (365 °F; 458 K)
Boiling point371 °C (700 °F; 644 K)
Solubility in water0.00051 g/L (20 °C)[1]
Solubility in other solventsbenzene, ether, petroleum ether, chloroform, hot acetic acid, ethanol (slightly), mineral oil (slightly)
Acidity (pKa)approx 23 in DMSO
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references
 
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Phenothiazine
Phenothiazin.svg
Phenothiazine-McDowell-3D-vdW.png
Phenothiazine-non-planar-McDowell-3D-balls.png
Identifiers
CAS number92-84-2 YesY
ChemSpider21106365 YesY
UNIIGS9EX7QNU6 YesY
KEGGD02601 YesY
ChEBICHEBI:37931 N
ChEMBLCHEMBL828 YesY
Jmol-3D imagesImage 1
Properties
Molecular formulaC12H9NS
Molar mass199.27 g/mol
Appearanceyellow rhombic leaflets or

diamond-shaped plates

Melting point185 °C (365 °F; 458 K)
Boiling point371 °C (700 °F; 644 K)
Solubility in water0.00051 g/L (20 °C)[1]
Solubility in other solventsbenzene, ether, petroleum ether, chloroform, hot acetic acid, ethanol (slightly), mineral oil (slightly)
Acidity (pKa)approx 23 in DMSO
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
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[edit]

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 diphenyl sulfide. Some of the pharmaceutically significant derivatives of phenothiazine are not prepared directly from phenothiazine,[2] although some of them are.[3]

Nondrug applications[edit]

The synthetic dye methylene blue, containing the structure, was described in 1876. Phenothiazine itself was introduced by DuPont as an insecticide in 1935.[4] 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 such as acryloyl chloride.[5]

Many water-soluble phenothiazine derivatives, such as methylene blue, methylene green, thionine, and others, can be electropolymerized into conductive polymers used as electrocatalysts for NADH oxidation in enzymatic biosensors and biofuel cells. [6][7][8]

Phenothiazine-derived drugs[edit]

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.[9][citation needed]

Phenothiazines, particularly prochlorperazine and chlorpromazine, are also used in emergency rooms to treat migraine and other intractable headaches.

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).

GroupAutonomicExampleSedativeExtrapyramidal side effects
Aliphatic compounds
moderateChlorpromazine (marketed as Thorazine, Chlor-PZ, Klorazine, Promachlor, Promapar, Sonazine, Chlorprom, Chlor-Promanyl, Largactil)strongmoderate
Promazine (trade name Sparine)moderatemoderate
Triflupromazine (trade names Clinazine, Novaflurazine, Pentazine, Terfluzine, Triflurin, Vesprin)strongmoderate/strong
Levomepromazine in Germany and methotrimeprazine in America (trade names Nozinan, Levoprome)extremely stronglow
PiperidinesstrongMesoridazine (trade name Serentil)strongweak
Thioridazine (trade names Mellaril, Novoridazine, Thioril)strongweak
PiperazinesweakFluphenazine (trade names Prolixin, Permitil, Modecate, Moditen)weak/moderatestrong
Perphenazine (sold as Trilafon, Etrafon, Triavil, Phenazine)weak/moderatestrong
Prochlorperazine (trade names Compazine, Stemetil)
Trifluoperazine (trade name Stelazine)moderatestrong


Trade Names[edit]

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, and Reconox.[10][11][12]

References[edit]

  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. ^ T. Kahl, K.-W. Schröder, F. R. Lawrence, W. J. Marshall, Hartmut Höke, Rudolf Jäckh, "Aniline" in Ullmann's Encyclopedia of Industrial Chemistry, 2005, Wiley-VCH: Weinheim.
  4. ^ History of Insecticides and Control Equipment Clemson University Pesticide Information Program.
  5. ^ PTZ Technical Information Bulletin Cytec PTZ Technical Information Bulletin
  6. ^ http://www.sciencedirect.com/science/article/pii/000326709485016X
  7. ^ http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291521-4109%28199906%2911:8%3C553::AID-ELAN553%3E3.0.CO;2-6/abstract
  8. ^ http://www.sciencedirect.com/science/article/pii/S0956566308003916
  9. ^ Rang; Dale et al., Pharmacology, 6th edition
  10. ^ U.S. Department of Labor Occupational Safety & Health Administration Chemical Sampling Information Phenothiazine
  11. ^ OSHA
  12. ^ PAN Pesticides Database

Further reading[edit]