7643-08-5

Usage

Chemical Properties

Off-White to Pale Yellow Solid

Uses

Phenothiazine derivative.

InChI:InChI=1/C13H11NS2/c1-15-9-6-7-13-11(8-9)14-10-4-2-3-5-12(10)16-13/h2-8,14H,1H3

Synthetic route

N-(3-methylthiophenyl)phenylamine (13313-45-6) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With iodine In acetone for 0.0133333h; Irradiation;	82%
With iodine; sulfur at 135℃; for 1h;

2-(2-fluorophenylthio)-5-(methylthio)aniline (129846-83-9) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With sodium hydride In xylene for 10h; Heating;	65%
Multi-step reaction with 2 steps 1: 89 percent / 4 h / Heating 2: 1.) K2CO3, 2.) 20percent ethanolic KOH / 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 6 h View Scheme

2-(2-bromophenylthio)-5-(methylthio)aniline (7623-78-1) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With copper; potassium carbonate In N,N-dimethyl-formamide for 15h; Heating;	55%

10H-phenothiazine-10-carbaldehyde (38076-67-4) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
In AlCl3	51%
In AlCl3	51%
In 1,1,2,2-tetrachloroethane	40%
In 1,1,2,2-tetrachloroethane	40%

N-(3-methylthiophenyl)phenylamine (13313-45-6) → 4-methylsulfanyl-phenothiazine (20349-56-8) + 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With iodine; sulfur at 160℃;

10H-phenothiazine-2-thiol (99970-41-9) + dimethyl sulfate (77-78-1) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With sodium hydroxide

2-methylsulfanyl-phenothiazine-10-carboxylic acid hydrazide (16868-91-0) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With butanone In ethanol Product distribution; Heating; other ketones : diethyl ketone, acetophenone;

3-Acetamino-1-methylmercapto-4-<2-brom-phenylmercapto>-benzol (5166-81-4) → 2-(methylthio)-10H-phenothiazine (7643-08-5) + 2-(methylyhio)-7-(2-(methylthio)phenothiazine-10-yl)-phenothiazine (129847-12-7)

Conditions	Yield
With potassium hydroxide; copper; potassium carbonate 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 5 h; Yield given. Multistep reaction. Yields of byproduct given;

2-(2-fluorophenylthio)-5-(methylthio)acetanilide (129846-84-0) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With potassium hydroxide; potassium carbonate 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 6 h; Yield given. Multistep reaction;

1-chloro-4-(methylthio)-2-nitrobenzene (1199-36-6) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 79 percent / NaOH / ethanol / 6 h / Heating 2: 1.) FeCl3*6H2O, active carbon, 2.) 80percent N2H4*H2O / 1.) ethanol, RT, 2.) RT, 10 h 3: 55 percent / K2CO3, Cu / dimethylformamide / 15 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 89 percent / K2CO3 / dimethylformamide / 3.5 h / 60 °C 2: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 3: 89 percent / 4 h / Heating 4: 1.) K2CO3, 2.) 20percent ethanolic KOH / 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 6 h View Scheme
Multi-step reaction with 3 steps 1: 89 percent / K2CO3 / dimethylformamide / 3.5 h / 60 °C 2: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 3: 65 percent / 80percent NaH / xylene / 10 h / Heating View Scheme

2-(2-bromophenolthio)-5-(methylthio)nitrobenzene (7623-76-9) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) FeCl3*6H2O, active carbon, 2.) 80percent N2H4*H2O / 1.) ethanol, RT, 2.) RT, 10 h 2: 55 percent / K2CO3, Cu / dimethylformamide / 15 h / Heating View Scheme

2-fluorothiophenol (2557-78-0) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: 89 percent / K2CO3 / dimethylformamide / 3.5 h / 60 °C 2: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 3: 89 percent / 4 h / Heating 4: 1.) K2CO3, 2.) 20percent ethanolic KOH / 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 6 h View Scheme
Multi-step reaction with 3 steps 1: 89 percent / K2CO3 / dimethylformamide / 3.5 h / 60 °C 2: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 3: 65 percent / 80percent NaH / xylene / 10 h / Heating View Scheme

2-bromothiophenol (6320-02-1) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 79 percent / NaOH / ethanol / 6 h / Heating 2: 1.) FeCl3*6H2O, active carbon, 2.) 80percent N2H4*H2O / 1.) ethanol, RT, 2.) RT, 10 h 3: 55 percent / K2CO3, Cu / dimethylformamide / 15 h / Heating View Scheme

2-(2-fluorophenylthio)-5-(methylthio)nitrobenzene (129846-82-8) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 2: 89 percent / 4 h / Heating 3: 1.) K2CO3, 2.) 20percent ethanolic KOH / 1.) DMF, reflux, 15 h, 2.) ethanol, reflux, 6 h View Scheme
Multi-step reaction with 2 steps 1: 99 percent / active carbon, N2H4, FeCl3*6H2O / ethanol / 10 h / Heating 2: 65 percent / 80percent NaH / xylene / 10 h / Heating View Scheme

3-methylmercaptoaniline (1783-81-9) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: copper-powder 3: iodine; sulfur / 160 °C View Scheme

2-benzylsulfanyl-10H-phenothiazine (101895-74-3) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium; butan-1-ol 2: aqueous NaOH View Scheme

N-(3'-methylthiophenyl)anthranylic acid (18902-93-7) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 2 steps 2: iodine; sulfur / 160 °C View Scheme

potassium 2-chlorobenzoate (16463-38-0) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: copper-powder 3: iodine; sulfur / 160 °C View Scheme

3-Bromothiophenol (6320-01-0) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. NaOH 2: Cu, K2CO3 / 220 - 230 °C 3: sulfur, I2 / 1 h / 135 °C View Scheme

3-bromo-1-(methylthio)benzene (33733-73-2) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: Cu, K2CO3 / 220 - 230 °C 2: sulfur, I2 / 1 h / 135 °C View Scheme

N-formyl-phenothiazine-2-sulfonyl chloride (139086-07-0) + dimethyl sulfate (77-78-1) + zinc (7440-66-6) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With sodium hydroxide; sulfuric acid In dichloromethane; water

10H-phenothiazine (92-84-2) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: Heating 2: sulfuric acid / Heating 3: zinc; acetic acid 4: potassium carbonate / acetone 5: sodium hydroxide; methanol View Scheme

10-acetyl-10H-phenothiazine (1628-29-1) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuric acid / Heating 2: zinc; acetic acid 3: potassium carbonate / acetone 4: sodium hydroxide; methanol View Scheme

C14H11NO4S2 → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: zinc; acetic acid 2: potassium carbonate / acetone 3: sodium hydroxide; methanol View Scheme

C14H11NOS2 → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / acetone 2: sodium hydroxide; methanol View Scheme

1-[2-(methylsulfanyl)-10H-phenothiazin-10-yl]ethanone (23503-69-7) → 2-(methylthio)-10H-phenothiazine (7643-08-5)

Conditions	Yield
With methanol; sodium hydroxide

2-(methylthio)-10H-phenothiazine (7643-08-5) + 1,3-chlorobromopropane (109-70-6) → 10-(3-chloropropyl)-2-(methylthio)-10H-phenothiazine (40256-12-0)

Conditions	Yield
With sodium hydride; potassium carbonate In tetrahydrofuran; mineral oil at 65℃; Inert atmosphere;	100%
Stage #1: 2-(methylthio)-10H-phenothiazine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.333333h; Inert atmosphere; Stage #2: 1.3-chlorobromopropane In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;	93%

2-(methylthio)-10H-phenothiazine (7643-08-5) + t-butyl 2-(2-bromoethyl)piperidine-1-carboxylate (210564-52-6) → C25H32N2O2S2

Conditions	Yield
With sodium hydride; potassium carbonate In tetrahydrofuran; mineral oil at 60℃; Inert atmosphere;	100%

1-bromo-butane (109-65-9) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → 10-butyl-2-(methylthio)-10H-phenothiazine (1353744-07-6)

Conditions	Yield
With potassium iodide; potassium hydroxide In dimethyl sulfoxide at 20℃; Inert atmosphere;	95%
With potassium iodide; potassium hydroxide In dimethyl sulfoxide at 20℃; for 0.0833333h;

2-(methylthio)-10H-phenothiazine (7643-08-5) + acetyl chloride (75-36-5) → 1-[2-(methylsulfanyl)-10H-phenothiazin-10-yl]ethanone (23503-69-7)

Conditions	Yield
In toluene at 20 - 30℃; for 1h; Temperature;	93%

2-(methylthio)-10H-phenothiazine (7643-08-5) → 1-(10H-phenothiazin-8-yl)hydrazine (1072135-10-4)

Conditions	Yield
With hydrazine hydrate for 8h; Reflux;	82%
With hydrazine Reflux;

2-(methylthio)-10H-phenothiazine (7643-08-5) + methyl 4-hydroxylbenzoate (99-76-3) → methyl 4-hydroxy-3-(2-(methylthio)-10H-phenothiazin-10-yl)benzoate

Conditions	Yield
With dipotassium hydrogenphosphate; oxygen; 10H-phenotellurazine In 1,2-dichloro-benzene at 130℃; for 3h; Reagent/catalyst; Sealed tube;	81%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 4-methoxy-benzoyl chloride (100-07-2) → 10-(4-methoxybenzoyl)-2-(methylthio)-10H-phenothiazine (1309924-82-0)

Conditions	Yield
In toluene Reflux;	79%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 6-(2-chloroethyl)-1-methyl-2-piperidinone (134356-29-9) → 10-<2-(1-methylpiperidin-2-on-6-yl)ethyl>-2-methylthio-10H-phenothiazine (89929-30-6)

Conditions	Yield
With sodium hydride In toluene for 22h; Heating;	78%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 4-Hydroxyacetophenone (99-93-4) → N-(2-hydroxy-5-acetylphenyl)-2-(thiomethyl)-10H-phenothiazine

Conditions	Yield
With dipotassium hydrogenphosphate; oxygen; 10H-phenotellurazine In 1,2-dichloro-benzene at 130℃; for 3h; Reagent/catalyst; Sealed tube;	77%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 4-hydroxythioanisole (1073-72-9) → N-(2-hydroxy-5-(thiomethyl)phenyl)-2-(thiomethyl)-10H-phenothiazine

Conditions	Yield
With dipotassium hydrogenphosphate; oxygen; 10H-phenotellurazine In 1,2-dichloro-benzene at 130℃; for 3h; Reagent/catalyst; Sealed tube;	73%

Methyl 4-(bromomethyl)benzoate (2417-72-3) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → methyl 4-[(2-methylthio-10H-phenothiazin-10-yl)methyl]benzoate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere;	69%

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%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 1,3-chlorohalopropane → 10-(3-chloropropyl)-2-(methylthio)-10H-phenothiazine (40256-12-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 100℃; for 24h; Sealed tube; Schlenk technique; Inert atmosphere;	53%

2-(methylthio)-10H-phenothiazine (7643-08-5) + N,N-diethylaniline (91-66-7) → N,N-diethyl-4-(2-(methylthio)-10H-phenothiazin-10-yl)aniline

Conditions	Yield
With tert-butylammonium hexafluorophosphate(V) In acetonitrile at 20℃; for 3h; Electrolysis;	50%

2-(methylthio)-10H-phenothiazine (7643-08-5) + 1,4-chlorohalobutane → 10-(4’-chlorobutyl)-2-methylthio-10H-phenothiazine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 100℃; for 24h; Sealed tube; Schlenk technique; Inert atmosphere;	25.6%

phosgene (75-44-5) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → 2-methylsulfanyl-phenothiazine-10-carbonyl chloride (92161-48-3)

Conditions	Yield
With benzene

2-(methylthio)-10H-phenothiazine (7643-08-5) + 2-(dimethylamino)ethyl chloride (107-99-3) → dimethyl-[2-(2-methylsulfanyl-phenothiazin-10-yl)-ethyl]-amine (107273-41-6)

Conditions	Yield
With sodium hydroxide; toluene
With sodium amide; xylene

2-(methylthio)-10H-phenothiazine (7643-08-5) + 1-diethylamino-2-chloropropane (761-21-7) → diethyl-[β-(2-methylsulfanyl-phenothiazin-10-yl)-isopropyl]-amine (110150-17-9)

Conditions	Yield
With sodium amide; xylene
With sodium hydroxide; toluene

oxirane (75-21-8) + 2-(methylthio)-10H-phenothiazine (7643-08-5) + 1-(3-chloro-propyl)-4-formyl-piperazine; hydrochloride + acetyl chloride (75-36-5) → 1-acetoxy-2-{4-[3-(2-methylsulfanyl-phenothiazin-10-yl)-propyl]-piperazin-1-yl}-ethane (103756-91-8)

Conditions	Yield
(i) NaNH2, (ii) aq. NaOH, (iii) /BRN= 102378/, MeOH, (iv) /BRN= 605303/; Multistep reaction;

3-(N-methylpiperazinyl)propyl chloride (104-16-5) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → 10-(3-(4-methylpiperazin-1-yl)propyl)-2-(methylthio)-10H-phenothiazine (14978-58-6)

Conditions	Yield
With sodium amide

1-(3-chloro-2-methyl-propyl)-4-methyl-piperazine (39607-92-6) + 2-(methylthio)-10H-phenothiazine (7643-08-5) → 10-[2-methyl-3-(4-methyl-piperazin-1-yl)-propyl]-2-methylsulfanyl-10H-phenothiazine (106439-16-1)

Conditions	Yield
With sodium amide

2-(methylthio)-10H-phenothiazine (7643-08-5) + trans-2-bromo-cyclopropanecarboxylic acid dimethylamide (17824-40-7, 31191-78-3, 31191-79-4) → dimethyl-[trans-2-(2-methylsulfanyl-phenothiazin-10-yl)-cyclopropylmethyl]-amine (47276-01-7)

Conditions	Yield
(i) NaH, DMSO, (ii) LiAlH4, Et2O; Multistep reaction;

Upstream product

• 13313-45-6 N-(3-methylthiophenyl)phenylamine 
• 16868-91-0 2-methylsulfanyl-phenothiazine-10-carboxylic acid hydrazide 
• 5166-81-4 3-Acetamino-1-methylmercapto-4-<2-brom-phenylmercapto>-benzol 
• 6320-01-0 3-Bromothiophenol 
• 139086-07-0 N-formyl-phenothiazine-2-sulfonyl chloride 
• 77-78-1 dimethyl sulfate 
• 7440-66-6 zinc 
• 38076-67-4 10H-phenothiazine-10-carbaldehyde 
• 23503-69-7 1-[2-(methylsulfanyl)-10H-phenothiazin-10-yl]ethanone 
• 1628-29-1 10-acetyl-10H-phenothiazine 
• 92-84-2 10H-phenothiazine 
• 1783-81-9 3-methylmercaptoaniline 
• 129846-82-8 2-(2-fluorophenylthio)-5-(methylthio)nitrobenzene 
• 6320-02-1 o-bromothiophenol 

Downstream Products

• 7009-43-0 dimethyl-[2-methyl-3-(2-methylsulfanyl-phenothiazin-10-yl)-propyl]-amine 
• 1039-59-4 10-(3-Dimethylamino-propyl)-3-methylmercapto-phenothiazin 
• 65010-93-7 2-chloro-1-(2-(methylthio)-10H-phenothiazin-10-yl)ethanone 
• 38642-74-9 10H-phenothiazine-2-carbonitrile 
• 40051-30-7 10-(3-chloropropyl)-2-(methylsulfonyl)-10H-phenothiazine 
• 18182-00-8 metopimazine acid 
• 14008-44-7 metopimazine 
• 1580464-39-6 4-(3-chlorophenyl)-3-methyl-1-(10H-phenothiazin-2-yl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-amine 
• 1580464-38-5 4-(2-chlorophenyl)-3-methyl-1-(10H-phenothiazin-2-yl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-amine 
• 1580464-37-4 4-(6-amino-3-methyl-1-(10H-phenothiazin-2-yl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenol 
• 1580464-36-3 3-(6-amino-3-methyl-1-(10H-phenothiazin-2-yl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenol 
• 1580464-35-2 2-(6-amino-3-methyl-1-(10H-phenothiazin-2-yl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenol 
• 1580464-34-1 3-methyl-1-(10H-phenothiazin-2-yl)-4-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-amine 

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MODIFIED SYNTHESES OF 2-(METHYLTHIO)-10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)PHENOTHIAZINE (THIORIDAZINE) AND 1-(3-(2-(METHYLSULFONYL)-10-PHENOTHIAZINYL)PROPYL)-PIPERIDINE-4-CARBOXAMIDE (METOPIMAZINE)

Modified syntheses