154-86-9

Hazards Identification

Pictogram(s):

Signal:

Warning

GHS Hazard Statements:

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]
H312 (100%): Harmful in contact with skin [Warning Acute toxicity, dermal]
H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]

Precautionary Statement Codes:

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P321, P330, P332+P317, P337+P317, P362+P364, and P501

Hazard Classes and Categories:

Acute Tox. 4 (100%)
Skin Irrit. 2 (100%)
Eye Irrit. 2 (100%)

Usage

InChI:InChI=1/C9H13NO2.ClH/c1-10-6-9(12)7-3-2-4-8(11)5-7;/h2-5,9-12H,6H2,1H3;1H

Synthetic route

(-)-phenylephedrine hydrochloride (61-76-7, 154-86-9, 939-38-8, 20368-45-0) → phenylephrine hydrochloride (154-86-9)

Conditions	Yield
With hydrogenchloride at 30.1℃; Rate constant;

phenylephrine hydrochloride (154-86-9) → 3-(1-Chloro-2-methylamino-ethyl)-phenol; hydrochloride

Conditions	Yield
With thionyl chloride In benzene	62%

phenylephrine hydrochloride (154-86-9) + chloroformic acid ethyl ester (541-41-3) → [2-Hydroxy-2-(3-hydroxy-phenyl)-ethyl]-methyl-carbamic acid ethyl ester

Conditions	Yield
With triethylamine In tetrahydrofuran for 1h;

phenylephrine hydrochloride (154-86-9) + sodium tetrakis[(3,5-di-trifluoromethyl)phenyl]borate (79060-88-1) → C32H12BF24(1-)*C9H13NO2*H(1+)

Conditions	Yield
In chloroform

phenylephrine hydrochloride (154-86-9) → {2-Hydroxy-2-[3-(quinolin-2-ylmethoxy)-phenyl]-ethyl}-carbamic acid ethyl ester (110193-32-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 1 h 2: 11 percent / cesium carbonate / acetone / 48 h / Heating View Scheme

phenylephrine hydrochloride (154-86-9) → 3-<2-(methylamino)ethyl>phenol hydrochloride (33543-61-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 62 percent / SOCl2 / benzene 2: H2 / Pd-black / ethanol / 20 °C View Scheme

(R)-2-(6-methoxy-2-naphthyl)propionic acid (23979-41-1) + phenylephrine hydrochloride (154-86-9) → (S)-phenylephrine-(R)-naproxen (1280541-43-6) + (R)-phenylephrine-(R)-naproxen (1280541-42-5)

Conditions	Yield
Stage #1: phenylephrine hydrochloride With sodium hydroxide In methanol at 20℃; for 0.5h; Stage #2: (R)-2-(6-methoxy-2-naphthyl)propionic acid In methanol at 25 - 60℃; for 1.5h; Product distribution / selectivity; Resolution of racemate;

phenylephrine hydrochloride (154-86-9) → phenylephrine hydrochloride (61-76-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / methanol / 0.5 h / 20 °C 1.2: 1.5 h / 25 - 60 °C / Resolution of racemate 2.1: hydrogenchloride / toluene; water / 0.5 h / 75 - 80 °C / pH < 2 2.2: 1 - 15 °C / pH ~ 9 3.1: hydrogenchloride / isopropyl alcohol / 0.5 h / 55 - 65 °C View Scheme

phenylephrine hydrochloride (154-86-9) → (S)-phenylephrine (614-03-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol / 0.5 h / 20 °C 1.2: 1.5 h / 25 - 60 °C / Resolution of racemate 2.1: sodium hydroxide / water 2.2: pH < 2 2.3: pH 9 View Scheme

Upstream product

• 61-76-7 (-)-phenylephedrine hydrochloride 

Downstream Products

• 110193-32-3 {2-Hydroxy-2-[3-(quinolin-2-ylmethoxy)-phenyl]-ethyl}-carbamic acid ethyl ester 
• 33543-61-2 3-<2-(methylamino)ethyl>phenol hydrochloride 
• 1280541-43-6 (S)-phenylephrine-(R)-naproxen 
• 1280541-42-5 (R)-phenylephrine-(R)-naproxen 
• 61-76-7 phenylephrine hydrochloride 
• 614-03-9 (S)-phenylephrine 
• 154-86-9 phenylephrine hydrochloride 

Relevant academic research and scientific papers

The acid-catalysed racemisation mechanism of catecholamines

The racemisation rates of (-)-adrenaline (1), ()-isoprenaline (2), (-)-2-(3,4-dimethoxyphenyl)-2-hydroxy-N-isopropylamine (3), (+)-2-(4-meethoxyphenyl)-2-hydroxy-N-isopropylethylamine (4), (+)-2-phenyl-2-hydroxy-N-isopropylehylamine (5), ()-phenylephrine(6), and (+)-1-phenylethanol(7) were compared. The racemisatton rates decreased in the following order: 7> 1 ≈ 2 > 3 ≈ 4 ? 5, 6. In general, the reactivity of the series of the phenylethanolamine compounds (1) - (6) was seen to increase sharply as the electron-releasing ability of the p-substituent of the aromatic nucleus increases. The results strengthen the notion that the acid-catalysed racemisation of catecholamines proceeds via a quinonoid-type intermediate.