38642-74-9

Basic information

• Product Name: 2-Cyano-phenothiazine
• Synonyms: PHENOTHIAZINE-2-CARBONITRILE;10H-PHENOTHIAZINE-2-CARBONITRILE;2-CYANO-PHENOTHIAZINE;2-PHENOTHIAZINECARBONITRILE;2-CYANO PHENOTHIAZINE,98.5+%;10H-PHENOTHIAZINE-3-CARBONITRILE;2-Cyanophenothazine;2-Cyano-10H-phenothiazine
• CAS NO: 38642-74-9
• Molecular Formula: C₁₃H₈N₂S
• Molecular Weight: 224.28
• EINECS: 254-057-3
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 38642-74-9.mol
• Article Data: 10

Chemical Properties

• Melting Point: 191-193°C
• Boiling Point: 427.6 °C at 760 mmHg
• Flash Point: 212.4 °C
• Appearance: Yellow Solid
• Density: 1.38 g/cm³
• Vapor Pressure: 1.62E-07mmHg at 25°C
• Refractive Index: 1.742
• Storage Temp.: Refrigerator
• Solubility: Chloroform
• PKA: -3.04±0.20(Predicted)
• CAS DataBase Reference: 2-Cyano-phenothiazine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Cyano-phenothiazine(38642-74-9)
• EPA Substance Registry System: 2-Cyano-phenothiazine(38642-74-9)

Safety Data

• Hazardous Substances Data: 38642-74-9(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Uses

Intermediate in the preparation of Cyamemazine, an antipsychotic agent.

InChI:InChI=1/C13H8N2S/c14-8-9-5-6-13-11(7-9)15-10-3-1-2-4-12(10)16-13/h1-7,15H

Synthetic route

2-chlorophenothiazine (92-39-7) + carbon dioxide (124-38-9) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With nickel(II) acetylacetonate; potassium fluoride; phenylsilane; ammonia; zinc; bis(2-diphenylphosphinoethyl)phenylphosphine In 1-methyl-pyrrolidin-2-one at 90 - 140℃; under 760.051 Torr; for 20h; Sealed tube;	94%

2-chlorophenothiazine (92-39-7) + copper(I) cyanide (544-92-3) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With p-toluenesulfonyl chloride; sodium iodide; lithium iodide In quinoline at 120 - 230℃; for 16h; Reagent/catalyst; Temperature;	92.6%

2-chlorophenothiazine (92-39-7) + copper(l) cyanide → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With potassium iodide; lithium iodide In cyclohexane at 85 - 218℃; for 10h; Solvent; Inert atmosphere;	90.2%

4-cyanobenzoic acid methyl ester (1129-35-7) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0); 1,2-bis-(dicyclohexylphosphino)ethane In o-xylene at 140℃; for 24h; Glovebox; Inert atmosphere;	54%

4-((2-aminophenyl)thio)-3-fluorobenzonitrile (214483-59-7) → 10H-phenothiazine-2-carbonitrile (38642-74-9) + 10H-phenothiazine-3-carbonitrile (28140-93-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 100℃; for 3h;	A 24% B 52%

4-((2-aminophenyl)thio)-3-fluorobenzonitrile (214483-59-7) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
In N,N-dimethyl-formamide at 140℃; for 48h;	30%

phenothiazine-2-carboxamide (1778-82-1) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With trichlorophosphate Heating;
With trichlorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 1h;

2-(3'-cyanophenylaminophenyl)disulfide (151079-75-3) → 10H-phenothiazine-2-carbonitrile (38642-74-9) + 2-mercapto 3'-cyanodiphenylamine (151079-72-0) + 4-cyanophenothiazine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 110℃; for 0.666667h; Yield given. Yields of byproduct given;

2-chlorophenothiazine (92-39-7) + Cu(CN)2 → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With quinoline

3,4-Difluorobenzonitrile (64248-62-0) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, 0 deg C, 12 h 2: 30 percent / dimethylformamide / 48 h / 140 °C View Scheme
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, 0 deg C, 12 h 2: 24 percent / NaH / dimethylformamide / 3 h / 100 °C View Scheme

2-amino-benzenethiol (137-07-5) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, 0 deg C, 12 h 2: 30 percent / dimethylformamide / 48 h / 140 °C View Scheme
Multi-step reaction with 2 steps 1: 1.) NaH / 1.) DMF, 0 deg C, 0.5 h, 2.) DMF, 0 deg C, 12 h 2: 24 percent / NaH / dimethylformamide / 3 h / 100 °C View Scheme

10H-phenothiazine-2-carboxylic acid (25234-50-8) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) PCl5, benzene, (ii) NH3 2: POCl3 / Heating View Scheme

2-chlorophenothiazine (92-39-7) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium iodide / 1-methyl-pyrrolidin-2-one / Reflux 2: trichlorophosphate / N,N-dimethyl-formamide / 1 h / 0 - 20 °C View Scheme

C13H9FN2S*Fe(3+)*C6H5O7(3-) → 10H-phenothiazine-2-carbonitrile (38642-74-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 110℃; Green chemistry; regioselective reaction;

di-tert-butyl dicarbonate (24424-99-5) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → tert-butyl 2-cyano-10H-phenothiazine-10-carboxylate

Conditions	Yield
Stage #1: 10H-phenothiazine-2-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.25h; Stage #2: di-tert-butyl dicarbonate In N,N-dimethyl-formamide at 20℃; for 3h;	100%
Stage #1: 10H-phenothiazine-2-carbonitrile With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Inert atmosphere; Stage #2: di-tert-butyl dicarbonate In N,N-dimethyl-formamide; mineral oil at 20℃; Inert atmosphere;	75%
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 18h;	72%

3,4,5-trimethylphenol (527-54-8) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → C22H18N2OS

Conditions	Yield
With oxygen In acetic acid at 150℃; for 24h; Sealed tube;	98%

3,4-dimethoxyphenol (2033-89-8) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → C21H16N2O3S

Conditions	Yield
With dipotassium peroxodisulfate In acetonitrile at 20℃; for 72h; Irradiation;	94%

10H-phenothiazine-2-carbonitrile (38642-74-9) + N,N-diethylaniline (91-66-7) → 10-(4-(diethylamino)phenyl)-10H-phenothiazine-2-carbonitrile

Conditions	Yield
With tert-butylammonium hexafluorophosphate(V) In acetonitrile at 20℃; for 3h; Electrolysis;	94%

10H-phenothiazine-2-carbonitrile (38642-74-9) → 10H-phenothiazine-2-carboxylic acid (25234-50-8)

Conditions	Yield
With hydrogenchloride; acetic acid at 117℃; for 18h; Inert atmosphere;	92%
With hydrogenchloride; acetic acid at 120℃; for 18h;	90%
With hydrogenchloride; water In methanol at 100℃;

2-phenyl-indole (948-65-2) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → C27H17N3S

Conditions	Yield
With copper(I) bromide In N,N-dimethyl-formamide at 60℃; for 24h; Schlenk technique;	83%
With copper(I) bromide In N,N-dimethyl-formamide at 60℃; for 24h;	83%

10H-phenothiazine-2-carbonitrile (38642-74-9) + 4-chloro-phenol (106-48-9) → C19H11ClN2OS

Conditions	Yield
With sodium periodate; acetic acid In dichloromethane at 40℃; for 24h; Inert atmosphere;	80%

Methyl 4-(bromomethyl)benzoate (2417-72-3) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → methyl 4-[(2-cyano-10H-phenothiazin-10-yl)methyl]benzoate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;	79%

10H-phenothiazine-2-carbonitrile (38642-74-9) + 4-methoxy-phenol (150-76-5) → 2-cyano-N-(2-hydroxy-5-methoxyphenyl)-10H-phenothiazine

Conditions	Yield
With tetrabutylammonium tetrafluoroborate In methanol; acetonitrile at 20℃; for 1.66667h; Electrochemical reaction; Inert atmosphere;	67%

indole (120-72-9) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → C21H13N3S

Conditions	Yield
With copper(I) bromide In N,N-dimethyl-formamide at 60℃; for 24h;	66%

10H-phenothiazine-2-carbonitrile (38642-74-9) → 10H-phenothiazine-2-carbaldehyde (14604-09-2)

Conditions	Yield
With diisobutylaluminium hydride In dichloromethane at -78 - 20℃; for 16h;	63%

10H-phenothiazine-2-carbonitrile (38642-74-9) + N,N-dimethyl-aniline (121-69-7) → C21H17N3S

Conditions	Yield
With dipotassium peroxodisulfate In acetonitrile at 20℃; for 1h; Schlenk technique;	54%

10H-phenothiazine-2-carbonitrile (38642-74-9) + N-phenyl-di-p-tolylamine (20440-95-3) → C33H25N3S

Conditions	Yield
With dipotassium peroxodisulfate In acetonitrile at 20℃; for 24h; Schlenk technique;	51%

10H-phenothiazine-2-carbonitrile (38642-74-9) + N-acetyl-L-tyrosine methyl ester (2440-79-1) → C25H21N3O4S

Conditions	Yield
With sodium sulfate In water; acetonitrile at 20℃; for 1.25h; Inert atmosphere; Electrolysis; Electrochemical reaction;	46%

10H-phenothiazine-2-carbonitrile (38642-74-9) + methyl (2E)-3-[4-(bromomethyl)phenyl]methacrylate (88738-86-7) → methyl (E)-3-[4-(2-cyano-10H-phenothiazin-10-ylmethyl)phenyl]acrylate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 7h; Inert atmosphere;	42%

4-HYDROXYPIPERIDINE (5382-16-1) + 10H-phenothiazine-2-carbonitrile (38642-74-9) + 1,3-chlorobromopropane (109-70-6) → periciazine (2622-26-6)

Conditions	Yield
Stage #1: 10H-phenothiazine-2-carbonitrile; 1.3-chlorobromopropane With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; for 7h; Stage #2: 4-HYDROXYPIPERIDINE With triethylamine In N,N-dimethyl-formamide at 0 - 60℃; for 42h;	40%

10H-phenothiazine-2-carbonitrile (38642-74-9) + 2-(3-iodo-2-methylpropyl)isoindoline-1,3-dione (1590417-40-5) → 10-(3-(1,3-dioxoisoindolin-2-yl)-2-methylpropyl)-10H-phenothiazine-2-carbonitrile (1590417-42-7)

Conditions	Yield
Stage #1: 10H-phenothiazine-2-carbonitrile With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: 2-(3-iodo-2-methylpropyl)isoindoline-1,3-dione In N,N-dimethyl-formamide at 0 - 20℃; for 16.5h;	15%

3-(N-methylpiperazinyl)propyl chloride (104-16-5) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → Propericiazin (67262-38-8)

Conditions	Yield
With sodium amide; xylene

phosgene (75-44-5) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → 2-cyano-phenothiazine-10-carbonyl chloride (92167-31-2)

Conditions	Yield
With toluene at 110℃;

N-(γ-chloro-isobutyl)-N-methyl-formamide (89583-17-5) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → N-Demethylcyamemazine (108014-19-3)

Conditions	Yield
With sodium amide; xylene anschliessendes Erwaermen mit wss.-methanol. HCl und Behandeln mit Maleinsaeure; dextrorotatory maleate;

1,3-bis(dimethylamino)-2-chloropropane (40550-12-7) + 10H-phenothiazine-2-carbonitrile (38642-74-9) → 10-(β,β'-bis-dimethylamino-isopropyl)-phenothiazine-2-carbonitrile (110332-67-7) + 10-(2,3-bis-dimethylamino-propyl)-phenothiazine-2-carbonitrile (102458-81-1)

Conditions	Yield
With sodium amide; xylene

10H-phenothiazine-2-carbonitrile (38642-74-9) + 2-chloro-1-dimethylaminopropane (108-14-5) → 10-(2-dimethylamino-propyl)-10H-phenothiazine-2-carbonitrile (7625-08-3)

Conditions	Yield
With sodium amide; xylene

10H-phenothiazine-2-carbonitrile (38642-74-9) + 3-(Dimethylamino)propyl chloride (109-54-6) → 10-(3-(dimethylamino)propyl)-10H-phenothiazine-2-carbonitrile (7678-64-0)

Conditions	Yield
Reaktion ueber mehrere Stufen;

10H-phenothiazine-2-carbonitrile (38642-74-9) + 3-(dimethylamino)-2-methylpropylchloride (23349-86-2) → cyamemazine (3546-03-0)

Conditions	Yield
(i) NaNH2, toluene, (ii) /BRN= 506000/; Multistep reaction;

Upstream product

• 1778-82-1 phenothiazine-2-carboxamide 
• 151079-75-3 2-(3'-cyanophenylaminophenyl)disulfide 
• 214483-59-7 4-((2-aminophenyl)thio)-3-fluorobenzonitrile 
• 92-39-7 2-chlorophenothiazine 
• 64248-62-0 3,4-Difluorobenzonitrile 
• 137-07-5 2-amino-benzenethiol 
• 25234-50-8 10H-phenothiazine-2-carboxylic acid 
• 544-92-3 copper(I) cyanide 
• 124-38-9 carbon dioxide 
• 1129-35-7 4-cyanobenzoic acid methyl ester 
• 7643-08-5 2-(methylthio)-10H-phenothiazine 
• 557-21-1 zinc(II) cyanide 
• 583-53-9 2,3-dibromobenzene 
• 101420-79-5 4-iodo-3-nitrobenzonitrile 

Downstream Products

• 3546-03-0 cyamemazine 
• 63457-22-7 10-(3'-chloropropyl)-2-cyano-10H-phenothiazine 
• 2622-26-6 periciazine 
• 3546-03-0 (+)-2-cyano-10-(3-dimethylamino-2-methylpropyl)phenothiazine 
• 7678-64-0 cyanopromazine 

Relevant articles and documents

Synthesis method of 2-cyanophenothiazine

The invention discloses a synthesis method of 2-cyanophenothiazine. The method comprises the following steps of: step 1, taking 4-halo-3-nitrobenzonitrile as a raw material, and performing a reaction in the presence of sulfide to obtain 3-amino-4-sulfydryl cyanophenyl; and 2, in the presence of nickel salt, ligand and alkali, making the 3-amino-4-sulfydryl cyanophenyl react with a compound C to generate 2-cyanophenothiazine. The 4-halo-3-nitrobenzonitrile which is low in price and easy to obtain serves as a raw material, and the synthesis of 2-cyanophenothiazine is achieved through few two steps. The reagent used in the reaction process is cheap and easy to obtain; and the reaction process is short in step; and the method has the advantages of simple and convenient operation, high yield, safe operation and no pollution, and is suitable for industrial production.

Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers

We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.

Efficient and regioselective synthesis of phenothiazine via ferric citrate catalyzed C-S/C-N cross-coupling

Efficient C-S and C-N cross-coupling reactions have been developed for regioselective, scalable and environmentally benign synthesis of substituted phenothiazine derivatives. Cross-coupling reactions were demonstrated on various challenging substrates using non-toxic, highly economical, readily available ferric citrate as a catalyst to get desired product with high regioselectivity. Atom economy is the added advantage of this protocol since additional N-protection step before coupling and eventual deprotection of the same to obtain the desired product arenot required. To the best of our knowledge, this is the first report on the use of inexpensive ferric citrate as a catalyst without involving any ligand for the synthesis of regioselectively substituted phenothiazine.