835-31-4

Basic information

• Product Name: Naphazoline
• Synonyms: 4,5-DIHYDRO-2-(1-NAPHTHYLMETHYL)-1H-IMIDAZOLE HYDROCHLORIDE;2-(1-NAPHTHYLMETHYL)-2-IMIDAZOLINE HYDROCHLORIDE;2-(1-NAPHTHYLMETHYL)IMIDAZOLINIUM CHLORIDE;1H-Imidazole, 4,5-dihydro-2-(1-naphthalenylmethyl)-;2-(1-Naphethylmethyl)-2-imidazoline;2-(1-naphthylmethyl)-2-imidazolin;2-(1-Naphthylmethyl)-2-imidazoline;2-(1-Naphthylmethyl)-4,5-dihydro-1H-imidazole
• CAS NO: 835-31-4
• Molecular Formula: C₁₄H₁₄N₂
• Molecular Weight: 246.74
• EINECS: 212-641-5
• Product Categories: API
• Mol File: 835-31-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 254 °C
• Boiling Point: 339.81°C (rough estimate)
• Flash Point: 220.186 °C
• Appearance: /
• Density: 1.1063 (rough estimate)
• Vapor Pressure: 1.52E-07mmHg at 25°C
• Refractive Index: 1.6180 (estimate)
• Storage Temp.: 2-8°C
• PKA: pKa 10.35 ± 0.02(H2O,t =25,Iundefined) (Uncertain)
• CAS DataBase Reference: Naphazoline(CAS DataBase Reference)
• NIST Chemistry Reference: Naphazoline(835-31-4)
• EPA Substance Registry System: Naphazoline(835-31-4)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: NJ4375000
• Hazardous Substances Data: 835-31-4(Hazardous Substances Data)

Usage

Originator

Privine,Ciba,US,1942

Uses

Naphazoline is used in severe rhinitis associated with colds, allergic reactions, and severe and chronic inflammatory conditions, in particular for inflammation of the antrum of Highmore as well as for stopping nosebleeds.

Manufacturing Process

2.7 parts of naphthyl-(1)-acetiminoethylether hydrochloride of the formula (produced from naphthyl-(1)-acetonitrile and methanol) are dissolved in 12 parts of absolute alcohol. 1 part of ethylenediamine is then added and the whole is heated to gentle boiling while passing nitrogen through it and simultaneously stirring until ammonia escapes no longer. The alcohol is then distilled and the residue mixed with 40 parts of benzene and 1.8 parts of caustic potash. Stirring is continued for some time whereby the imidazoline base is dissolved in benzene. The benzene residue is recrystallized several times from toluene.

Synthesis

Naphazoline, 2-(1-naphthylmethyl)-2-imidazoline (11.1.36), is synthesized from (1-naphthyl)acetonitrile, which upon reaction with ethanol transforms into iminoester (11.1.35), and undergoes further heterocyclization into the desired imidozoline derivative (11.1.36) upon reaction with ethylendiamine [40].

InChI:InChI=1/C14H14N2/c1-2-7-13-11(4-1)5-3-6-12(13)10-14-15-8-9-16-14/h1-7H,8-10H2,(H,15,16)

Synthetic route

naphth-1-yl acetic acid (86-87-3) + ethylenediamine (107-15-3) → naphazoline (835-31-4)

Conditions	Yield
for 2h; Time; Reflux;	85%
With iron oxide In water; benzene at 80℃; for 4h;	30%

naphthalen-1-ylacetonitrile (132-75-2) + ethylene diamine mono-p-toluenesulfonic acid salt (14034-59-4) → naphazoline (835-31-4)

naphth-1-yl acetic acid (86-87-3) + 1,2-ethanediamine monohydrate (6780-13-8) → naphazoline (835-31-4)

Conditions	Yield
With hydrogenchloride

N-[1]naphthylacetyl-glycine nitrile → naphazoline (835-31-4)

Conditions	Yield
With ammonia; nickel; isopropyl alcohol at 70℃; under 73550.8 Torr; Hydrogenation.Erhitzen des Reaktionsprodukts unter vermindertem Druck;

naphthalen-1-ylacetonitrile (132-75-2) + ethanolamine (141-43-5) → naphazoline (835-31-4)

Conditions	Yield
With ammonium chloride; zinc(II) chloride

ethyl-[1]naphthylethynyl ether (100621-70-3) + ethylenediamine (107-15-3) → naphazoline (835-31-4)

naphthalen-1-ylacetonitrile (132-75-2) + ethylenediamine-mono hydrochloride → naphazoline (835-31-4)

1-naphthyl tosylate (68211-49-4) → naphazoline (835-31-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: diethyl ether View Scheme

naphthalen-1-ylacetonitrile (132-75-2) + ethylenediamine (107-15-3) → naphazoline (835-31-4)

Conditions	Yield
With carbon disulfide at 110℃; for 2h; Reagent/catalyst; Temperature;

naphazoline (835-31-4) → naphazoline hydrochloride (550-99-2)

Conditions	Yield
With hydrogenchloride In acetonitrile at 20℃; Solvent; Large scale;	92.33%
With hydrogenchloride In acetone at 5℃; for 0.5h; pH=1; Temperature; Reflux;

naphazoline (835-31-4) → Naphazole (1019-21-2)

Conditions	Yield
palladium on activated charcoal In toluene for 200h; Heating;	83%
palladium on activated charcoal In toluene for 216h; Heating;	83%

terephthalonitrile (623-26-7) + naphazoline (835-31-4) → C21H17N3

Conditions	Yield
With thiobenzoic acid; potassium phosphate In N,N-dimethyl acetamide at 20℃; for 6h; Irradiation;	67%

naphazoline (835-31-4) + acetic anhydride (108-24-7) → 1-acetyl-2-[1]naphthylmethyl-4,5-dihydro-1H-imidazole

Conditions	Yield
With pyridine

naphazoline (835-31-4) + acetic anhydride (108-24-7) → 1-acetyl-2-[1]naphthylmethyl-4,5-dihydro-1H-imidazole + 1-acetylamino-2-(2-[1]naphthyl-acetylamino)-ethane

Conditions	Yield
With pyridine

naphazoline (835-31-4) + acetic anhydride (108-24-7) → 1,3-diacetyl-2-[1]naphthylmethylene-imidazolidine

naphazoline (835-31-4) + benzoyl chloride (98-88-4) → 1,3-dibenzoyl-2-[1]naphthylmethylene-imidazolidine

Conditions	Yield
With benzene

naphazoline (835-31-4) → N-(1-naphthylacetyl)ethylenediamine (36321-43-4)

Conditions	Yield
With sodium hydroxide
With water

2-Chloronicotinoyl chloride (49609-84-9) + naphazoline (835-31-4) → 1-<(2-chloro-3-pyridinyl)carbonyl>-4,5-dihydro-2-(1-naphthalenyl)-1H-imidazole (124372-93-6)

Conditions	Yield
With triethylamine In dichloromethane

naphazoline (835-31-4) + di-tert-butyl dicarbonate (24424-99-5) → 2-Naphthalen-1-ylmethyl-4,5-dihydro-imidazole-1-carboxylic acid tert-butyl ester (126232-60-8)

Conditions	Yield
In tetrahydrofuran Ambient temperature; Yield given;

naphazoline (835-31-4) + chloranil (118-75-2) → 2-Naphthalen-1-ylmethyl-4,5-dihydro-1H-imidazole; compound with 2,3,5,6-tetrachloro-[1,4]benzoquinone

Conditions	Yield
In chloroform at 40℃; for 0.4h; Thermodynamic data; ΔG0;
In chloroform at 40℃; for 0.4h;

naphazoline (835-31-4) → Naphazolin-Iod-Komplex

Conditions	Yield
With iodine In chloroform for 0.5h; Ambient temperature;

naphazoline (835-31-4) → 2-(naphthalen-4-yl)methyl-4,5-dihydro-1H-imidazole radical

Conditions	Yield
With SO4-. radical In phosphate buffer at 22℃; pH=7.4; Kinetics; hydrogen abstraction;
With potassium peroxydiphosphate In water at 25℃; pH=7.1; Kinetics; Reagent/catalyst; Solvent; pH-value; Concentration; Inert atmosphere; Irradiation; aq. phosphate buffer;

2-(3-bromopropylamino)ethanol + naphazoline (835-31-4) → 2-[3-(2-naphthalen-1-ylmethyl-4,5-dihydro-imidazol-1-yl)-propylamino]-ethanol

Conditions	Yield
With triethylamine for 5h; Heating;

naphazoline (835-31-4) + 2-bromopropanol (598-18-5) → 1-(2-naphthalen-1-ylmethyl-4,5-dihydro-imidazol-1-yl)-propan-2-ol

Conditions	Yield
With triethylamine for 5h; Heating;

naphazoline (835-31-4) + 2-bromoethanol (540-51-2) → 2-(2-naphthalen-1-ylmethyl-4,5-dihydro-imidazol-1-yl)-ethanol

Conditions	Yield
With triethylamine for 5h; Heating;

naphazoline (835-31-4) → N-(2-bromoethyl)-2-[(1-naphthyl)methyl]-2-imidazoline

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / 5 h / Heating 2: HBr; CH3COOH / tetrahydrofuran / 1 h / Heating View Scheme

naphazoline (835-31-4) → 1-(2-bromopropyl)-2-[(1-naphthyl)methyl]-2-imidazoline

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / 5 h / Heating 2: HBr; CH3COOH / tetrahydrofuran / 1 h / Heating View Scheme

naphazoline (835-31-4) → 1-[N-(2-bromoethyl)-3-aminopropyl]-2-[1-naphthylmethyl]-2-imidazoline

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / 5 h / Heating 2: HBr; CH3COOH / tetrahydrofuran / 1 h / Heating View Scheme

naphazoline (835-31-4) → 3-(4,5-Dihydro-1H-imidazol-2-yl)-3-naphthalen-1-yl-propionic acid (126232-64-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrofuran / Ambient temperature 2: 1.) BuLi / 1.) THF, -78 deg C, 1 h, 2.) -78 deg C -> 20 deg C, 1 h, 20 deg C, 1 h 3: aq. HCl / acetic acid / 3 h / 40 °C View Scheme

naphazoline (835-31-4) → 2-(2-tert-Butoxycarbonyl-1-naphthalen-1-yl-ethyl)-4,5-dihydro-imidazole-1-carboxylic acid tert-butyl ester (126262-55-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / Ambient temperature 2: 1.) BuLi / 1.) THF, -78 deg C, 1 h, 2.) -78 deg C -> 20 deg C, 1 h, 20 deg C, 1 h View Scheme

Upstream product

• 132-75-2 naphthalen-1-ylacetonitrile 
• 14034-59-4 ethylene diamine mono-p-toluenesulfonic acid salt 
• 107-15-3 ethylenediamine 
• 86-87-3 naphth-1-yl acetic acid 
• 68211-49-4 1-naphthyl tosylate 
• 100621-70-3 ethyl-[1]naphthylethynyl ether 
• 141-43-5 ethanolamine 
• 6780-13-8 1,2-ethanediamine monohydrate 

Downstream Products

• 550-99-2 naphazoline hydrochloride 
• 36321-43-4 N-(1-naphthylacetyl)ethylenediamine 

Relevant articles and documents

Preparation method of naphazoline hydrochloride

The invention relates to the technical field of organic synthesis, in particular to a preparation method of naphazoline hydrochloride, which comprises the following steps: by using alpha-naphthylacetic acid, ethylenediamine and acetone as raw materials, carrying out condensation, cyclization, salification and the like to prepare 4, 5-dihydro-2-(1-naphthyl methyl)-1H-imidazole hydrochloride. Alpha-naphthylacetic acid, ethylenediamine and acetone are used as raw materials to prepare the target product, and the raw materials are easy to obtain and low in price. Condensation, cyclization and salification are adopted, the operation reaction conditions are mild, a large number of side reactions are avoided, and the high yield is obtained. The preparation process is high in coherence, short in time consumption and more efficient and thorough in reaction. The preparation process is simple, reaction conditions are mild, and environmental pollution is avoided.

Colloid and nanosized catalysts in organic synthesis: XIII. Synthesis of 2-R-2-imidazolines catalyzed by copper and iron oxide nanoparticles

The reaction of carboxylic acids with ethylenediamine catalyzed by copper or iron oxide nanoparticles proceeds at 80°C with azeotropic water distilling off during 2-8 h to form 2-R-2-imidazolines. Acyl and diacyl derivatives of ethylenediamine are formed in the reaction as side products.

Feed additive for improving growth in agricultural animals

By using α-mimetics, particularly compounds of general formulae I to III and the compounds listed in Table I, as feed additives in fattening animals, it has surprisingly been possible to improve the daily weight gain, the utilisation of fodder and the ratio of muscle to fat in favor of the proportion of muscle and protein.