73218-79-8

Basic information

• Product Name: Apraclonidine hydrochloride
• Synonyms: 2-(4-amino-2,6-dichlorophenylimino)imidazolidinehydrochloride;2,6-dichloro-n(sup1)-(2-imidazolidinylidene)-1,4-benzenediaminehydrochlorid;2,6-dichloro-n(sup1)-(4,5-dihydro-1h-imidazol-2-yl)-1,4-benzenediaminemonoh;3,5-dichloro-4-(2-imidazolidinylidenimino)anilinehydrochloride;4-benzenediamine,2,6-dichloro-n(sup1)-(4,5-dihydro-1h-imidazol-2-yl)-mono;alo-2145;iopidine;iopidineophthalmicsolution
• CAS NO: 73218-79-8
• Molecular Formula: C₉H₁₀Cl₂N₄*ClH
• Molecular Weight: 281.57
• Product Categories: Heterocyclic Compounds;Bases & Related Reagents;Heterocycles;Intermediates & Fine Chemicals;Nucleotides;Pharmaceuticals
• Mol File: 73218-79-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: >2300C
• Boiling Point: 395.5 °C at 760 mmHg
• Flash Point: 193 °C
• Appearance: white/solid
• Density: 1.63 g/cm³
• Storage Temp.: 2-8°C
• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 1.4 mg/mL
• Stability: Moisture Sensitive
• CAS DataBase Reference: Apraclonidine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Apraclonidine hydrochloride(73218-79-8)
• EPA Substance Registry System: Apraclonidine hydrochloride(73218-79-8)

Safety Data

• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 22-36/37/39-45
• RIDADR: UN 2811 6.1/PG 1
• WGK Germany: 3
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 73218-79-8(Hazardous Substances Data)

Usage

Chemical Properties

Crystalline Solid

Uses

Different sources of media describe the Uses of 73218-79-8 differently. You can refer to the following data:
1. a-Adrenergic agonist; structural analog of clonidine. Used for treatment of post-surgical elevated intraocular pressure
2. Apraclonidine hydrochloride can be used as α-Adrenergic agonist; structural analog of clonidine and be used for treatment of post-surgical elevated intraocular pressure.

Definition

ChEBI: The hydrochloride salt of apraclonidine.

Brand name

Iopidine (Alcon).

InChI:InChI=1/C9H10Cl2N4.ClH/c10-6-3-5(12)4-7(11)8(6)15-9-13-1-2-14-9;/h3-4H,1-2,12H2,(H2,13,14,15);1H

Synthetic route

p-aminoclonidine (66711-21-5) → 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8)

Conditions	Yield
With hydrogenchloride In methanol for 2h; Solvent; Reflux;	72.1%

4-nitro-2,6-dichloroaniline (99-30-9) → 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic anhydride / 1 h / 70 - 80 °C 1.2: 3 h / Heating 2.1: sulfuryl dichloride; thionyl chloride / 4 h / Reflux 3.1: triethylamine / ethyl acetate / 6 h / 5 °C 4.1: hydrazine hydrate; 5%-palladium/activated carbon / methanol / 2 h / Heating 5.1: hydrogenchloride / methanol / 2 h / Reflux View Scheme

N-(2,6-dichloro-4-nitrophenyl)formamide (70106-94-4) → 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: sulfuryl dichloride; thionyl chloride / 4 h / Reflux 2: triethylamine / ethyl acetate / 6 h / 5 °C 3: hydrazine hydrate; 5%-palladium/activated carbon / methanol / 2 h / Heating 4: hydrogenchloride / methanol / 2 h / Reflux View Scheme

(2,6-dichloro-4-nitrophenyl)carbonimidic dichloride (73218-65-2) → 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / ethyl acetate / 6 h / 5 °C 2: hydrazine hydrate; 5%-palladium/activated carbon / methanol / 2 h / Heating 3: hydrogenchloride / methanol / 2 h / Reflux View Scheme

fumaric acid ethyl ester mono chloride (26367-48-6) + 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8) → (trans beta-carbethoxyacrylamido)-4-clonidine (88307-13-5)

Conditions	Yield
In water at 50℃; for 0.25h;	55%

4-fluorophenylacetonitrile (459-22-3) + 2-[(4-amino-2,6-dichlorophenyl)imino]imidazolidine monohydrochloride (73218-79-8) → 2-[4-(4-Fluorobenzylamidino)-2,6-dichlorophenylimino]imidazolidine dihydrochloride

Conditions	Yield
aluminium chloride

Upstream product

• 73218-65-2 (2,6-dichloro-4-nitrophenyl)carbonimidic dichloride 
• 70106-94-4 N-(2,6-dichloro-4-nitrophenyl)formamide 
• 99-30-9 4-nitro-2,6-dichloroaniline 
• 66711-21-5 p-aminoclonidine 

Downstream Products

• 88307-13-5 (trans beta-carbethoxyacrylamido)-4-clonidine 

Relevant articles and documents

A α2 - Adrenergic receptor agonist hydrochloric acid an le decides and its preparation method

The invention relates to an alpha2-adrenergic receptor stimulant apraclonidine hydrochloride and a preparation method thereof. The structural formula is shown in the specification. The preparation comprises the following steps: 2, 6-dichloro-4-nitroaniline, formic acid and acetic anhydride are mixed, heated and stirred, react and recrystallize, N-(2, 6-dichloro-4-nitrophenyl) formamide is obtained and then stirred, flows back and reacts with sulfuryl chloride and thionyl chloride, N-(2, 6-dichloro-4-nitrophenyl) dichlorocarbamide is obtained and dropwise added to an ethyl acetate solution containing ethylenediamine and triethylamine, the mixture is stirred for reaction for 1-10 h under the condition of 5-8 DEG C, 2-(2',6'-dichloro-4'- nitroanilino)-2-imidazoline is prepared, then a reducing agent is added to the solvent for reduction, hydrochloric acid is finally added to a reaction liquid, and stirring and backflow are performed for 1.5 h for preparation. The preparation process is simple to operate, the yield is high, the cost is low, the reaction route is short, little three wastes are generated, and industrial production is facilitated.