30536-19-7

Basic information

• Product Name: 4-Amino-5-chloro-2,1,3-benzothiadiazole
• Synonyms: 4-AMINO-5-CHLORO-1,2,3-BENZOTHIADIAZOLE;5-Chloro-4-Amino-1,2,3-Benzothiadiazole;4-AMINO-5-CHLORO-2,1,3-BENZOTHIODIAZOLE;4-Amino-5-chloro-2,1,3-benzothiadiazole;5-Chloro-2,1,3-benzothiadiazol-4-ylamine;2,1,3-benzothiadiazol-4-amine, 5-chloro-;5-chlorobenzo[c][1,2,5]thiadiazol-4-amine;Tizanidine Related Compound A (50 mg) (4-amino-5-chloro-2,1,3-benzothiadiazole)
• CAS NO: 30536-19-7
• Molecular Formula: C₆H₄ClN₃S
• Molecular Weight: 185.63
• EINECS: 1308068-626-2
• Product Categories: Aromatics Compounds;Aromatics;Heterocycles;Tizanidine Hydrochloride;Amines;Sulfur & Selenium Compounds
• Mol File: 30536-19-7.mol
• Article Data: 1

Chemical Properties

• Melting Point: 89 °C
• Boiling Point: 316.4 °C at 760 mmHg
• Flash Point: 145.1 °C
• Appearance: white solid
• Density: 1.632 g/cm³
• Vapor Pressure: 0.000412mmHg at 25°C
• Refractive Index: 1.781
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: -0.16±0.48(Predicted)
• CAS DataBase Reference: 4-Amino-5-chloro-2,1,3-benzothiadiazole(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-5-chloro-2,1,3-benzothiadiazole(30536-19-7)
• EPA Substance Registry System: 4-Amino-5-chloro-2,1,3-benzothiadiazole(30536-19-7)

Safety Data

• Hazardous Substances Data: 30536-19-7(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

(Tizanidine EP Impurity E)

InChI:InChI=1/C6H4ClN3S/c7-3-1-2-4-6(5(3)8)10-11-9-4/h1-2H,8H2

Synthetic route

5-chloro-4-nito-2,1,3-benzothiadiazole (2274-89-7) → 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7)

Conditions	Yield
With iron
With iron; acetic acid In methanol

5-chloro-2,1,3-benzothiadiazole (2207-32-1) → 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: concentrated HNO3; concentrated H2SO4 2: iron View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid; nitric acid 2: iron; acetic acid / methanol View Scheme

1-acetylimidazolidin-2-one (5391-39-9) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → 5-chloro-N-(N-acetyl-4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine

Conditions	Yield
With trichlorophosphate In acetone at 50 - 55℃; for 20h; Temperature; Solvent;	93.6%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + potassium ethyl xanthogenate (140-89-6) + methyl iodide (74-88-4) → C8H5N3S3

Conditions	Yield
Stage #1: 4-amino-5-chloro-2,1,3-benzothiadiazole; potassium ethyl xanthogenate In N,N-dimethyl-formamide for 18h; Inert atmosphere; Reflux; Stage #2: methyl iodide In N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere;	91.5%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + 2-chloro-2-imidazoline hydrochloride (54255-14-0) → tizanidine (51322-75-9)

Conditions	Yield
With pyridine In iso-butanol at 65 - 70℃; for 8h; Temperature; Solvent; Reagent/catalyst;	90.5%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + acetic acid (64-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine acetate

Conditions	Yield
In isopropyl alcohol at -10 - 90℃; for 27h; Solvent; Temperature;	88.5%

LACTIC ACID (849585-22-4) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine 2-hydroxypropionic acid salt

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at -5 - 90℃; for 46h;	88.3%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) + hexanoic acid (142-62-1) → tizanidine hexanoate

Conditions	Yield
In ethanol; N,N-dimethyl-formamide at 0 - 80℃; for 29h;	87.5%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + malic acid (617-48-1) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine malate

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at 85 - 90℃; for 32.5h;	87.5%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + acetic acid (64-19-7) + methyl 2-(methylthio)-4,5-dihydro-1H-imidazole-1-carboxylate (60546-77-2) → tizanidine acetate

Conditions	Yield
In isopropyl alcohol at -5 - 95℃; for 28h;	87%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + oxalic acid (144-62-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine oxalate

Conditions	Yield
In methanol; N,N-dimethyl-formamide at 0 - 70℃; for 31h;	86.9%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + malonic acid (141-82-2) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine malonate

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at -10 - 90℃; for 38h; Solvent; Temperature;	86.8%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + 3-oxapentanoic acid (627-03-2) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine ethoxyacetate

Conditions	Yield
In methanol; N,N-dimethyl-formamide at -5 - 70℃; for 24h;	86.5%

glycolic Acid (79-14-1) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) → tizanidine glycolate

Conditions	Yield
In N,N-dimethyl-formamide; isopropyl alcohol at 5 - 90℃; for 41h;	86.2%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) + citric acid (77-92-9) → tizanidine citrate

Conditions	Yield
In ethanol; N,N-dimethyl-formamide at -5 - 80℃; for 40h;	86.1%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N-acetyl-2-ethylthio-2-imidazoline (61076-80-0) + butyric acid (107-92-6) → tizanidine butanoate

Conditions	Yield
In ethanol; N,N-dimethyl-formamide at -5 - 90℃; for 38h;	86%

1-acetylimidazolidin-2-one (5391-39-9) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → tizanidine hydrochloride (64461-82-1, 74113-36-3)

Conditions	Yield
Stage #1: 1-acetylimidazolidin-2-one; 4-amino-5-chloro-2,1,3-benzothiadiazole With trichlorophosphate at 60 - 65℃; for 36h; Stage #2: With methanol for 4h; Reflux; Stage #3: With hydrogenchloride In ethanol at 20℃; for 1h;	85%

1-acetylimidazolidin-2-one (5391-39-9) + sodium sulfate anhydride + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → tizanidine (51322-75-9)

Conditions	Yield
With trichlorophosphate In methanol; sodium hydroxide; water	73%

1-acetylimidazolidin-2-one (5391-39-9) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → tizanidine (51322-75-9)

Conditions	Yield
Stage #1: 1-acetylimidazolidin-2-one; 4-amino-5-chloro-2,1,3-benzothiadiazole With trichlorophosphate at 60 - 65℃; for 36h; Stage #2: With methanol; sodium hydroxide for 4h; Reflux;	70%

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + 2-oxo-propionic acid (127-17-3) → 8H-pyrrolo[2',3':3,4]benzo[1,2-c][1,2,5]thiadiazole-7-carboxylic acid (96450-32-7)

Conditions	Yield
With potassium phosphate; magnesium sulfate; acetic acid; bis(tri-t-butylphosphine)palladium(0) In N,N-dimethyl acetamide at 140℃; for 14h;	67%

N,N,N,N,N,N-hexamethylphosphoric triamide (680-31-9) + formic acid (64-18-6) + 4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C9H9ClN4S

Conditions	Yield
at 220 - 230℃; for 4h; Yield given;

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → C9H9ClN4S

Conditions	Yield
With trichlorophosphate In benzene Yield given;

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + dichloroamine → 5,7-dichloro-benzo[1,2,5]thiadiazol-4-ylamine (16407-86-6)

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) + ethyl bromoacetate (105-36-2) → C10H10ClN3O2S

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 24h;

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C8H6ClN3O2S

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 120 °C 2: lithium hydroxide; water / tetrahydrofuran View Scheme

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C17H22ClN5O3S

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 120 °C 2: lithium hydroxide; water / tetrahydrofuran 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol View Scheme

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C12H14ClN5OS

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 120 °C 2: lithium hydroxide; water / tetrahydrofuran 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol 4: hydrogenchloride / methanol View Scheme

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C15H16ClN5O2S

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 24 h / 120 °C 2: lithium hydroxide; water / tetrahydrofuran 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol 4: hydrogenchloride / methanol 5: triethylamine / dichloromethane View Scheme

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → 7-hydrazino-thiazolo[4',5':3,4]benzo[1,2-c][1,2,5]thiadiazole (91982-37-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: N,N-dimethyl-formamide / 18 h / Inert atmosphere; Reflux 1.2: 1 h / 0 °C / Inert atmosphere 2.1: hydrazine hydrate / propan-1-ol / 8 h / Inert atmosphere; Reflux View Scheme

4-amino-5-chloro-2,1,3-benzothiadiazole (30536-19-7) → C14H9N5O2S2

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N,N-dimethyl-formamide / 18 h / Inert atmosphere; Reflux 1.2: 1 h / 0 °C / Inert atmosphere 2.1: hydrazine hydrate / propan-1-ol / 8 h / Inert atmosphere; Reflux 3.1: propan-1-ol / 2 h / Inert atmosphere; Reflux View Scheme

Upstream product

• 2274-89-7 5-chloro-4-nito-2,1,3-benzothiadiazole 
• 2207-32-1 5-chloro-2,1,3-benzothiadiazole 

Downstream Products

• 16407-86-6 5,7-Dichlor-4-amino-benz<2,1,3>-thiadiazol 
• 51322-75-9 tizanidine 
• 91982-37-5 7-hydrazino-thiazolo[4',5':3,4]benzo[1,2-c][1,2,5]thiadiazole 
• 64461-82-1 tizanidine hydrochloride 
• 106314-85-6 tizanidine 2-hydroxypropionic acid salt 
• 173532-15-5 5-chloro-N-(N-acetyl-4,5-dihydro-1H-imidazol-2-yl)-2,1,3-benzothiadiazol-4-amine 

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