11041-94-4

Basic information

• Product Name: Demethyl
• Synonyms: Demethyl;1,2,3,4-Tetrahydro-1-((4-hydroxyphenyl)methyl)-6,7-isoquinolinediol hydrochloride;Higenamine hydrochloride;6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline;6,7-Dihydroxy-1-(4-Hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride;6,7-Isoquinolinediol,1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-, hydrochloride (1:1);1-(4-Hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol hydrochloride;norcoclaurine hcl
• CAS NO: 11041-94-4
• Molecular Formula: C₁₆H₁₇NO₃*ClH
• Molecular Weight: 307.77202
• EINECS: 1592732-453-0
• Mol File: 11041-94-4.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 522.4 °C at 760 mmHg
• Flash Point: 209.6 °C
• Appearance: white powder
• Vapor Pressure: 1.56E-11mmHg at 25°C
• CAS DataBase Reference: Demethyl(CAS DataBase Reference)
• NIST Chemistry Reference: Demethyl(11041-94-4)
• EPA Substance Registry System: Demethyl(11041-94-4)

Safety Data

• Hazardous Substances Data: 11041-94-4(Hazardous Substances Data)

Usage

Toxicity

The safety of orally administered higenamine hydrochloride in humans is unknown. During a study of acute toxicity, mice were orally administered the compound at a dose of 2 g per kg of bodyweight. No mice died during the study.In human trials of intravenous higenamine, subjects who received higenamine reported shortness of breath, racing heart, dizziness, headaches, chest tightness.

Description

Higenamine is a chemical found in several plants including aconite, Annona squamosa, Nandina domestica (sacred bamboo), and others. HigenaMine Hydrochloride is the hydrochloride form of higenamine.

Uses

Higenamine HCl (norcoclaurine) is a plant-based alkaloid widely used as nutritional supplement in food and beverage industries.

InChI:InChI=1/C16H17NO3.ClH/c18-12-3-1-10(2-4-12)7-14-13-9-16(20)15(19)8-11(13)5-6-17-14;/h1-4,8-9,14,17-20H,5-7H2;1H

Synthetic route

6,7-bisbenzyloxy-1-(4-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (117765-29-4) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol for 2h;

2-[4-(benzyloxy)phenyl]acetonitrile (838-96-0) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions

Yield

Multi-step reaction with 6 steps 1: potassium hydroxide, water / ethane-1,2-diol / 18 h / Heating 2: oxalyl chloride, DMF / benzene / 1 h / 20 °C 3: sodium hydrogen carbonate / CH2Cl2; H2O / 1.5 h 4: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 5: sodium borohydride / methanol / 0.75 h / 0 °C 6: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

3,4-bis(benzyloxy)-β-nitrostyrene (1699-54-3) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: 70 percent / lithium aluminium hydride / tetrahydrofuran / 1.25 h / Heating 2: sodium hydrogen carbonate / CH2Cl2; H2O / 1.5 h 3: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 4: sodium borohydride / methanol / 0.75 h / 0 °C 5: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

2-(4-(benzyloxy)phenyl)acetyl chloride (39188-62-0) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydrogen carbonate / CH2Cl2; H2O / 1.5 h 2: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 3: sodium borohydride / methanol / 0.75 h / 0 °C 4: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

2-[4-(benzyloxy)benzyl]acetic acid (6547-53-1) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: oxalyl chloride, DMF / benzene / 1 h / 20 °C 2: sodium hydrogen carbonate / CH2Cl2; H2O / 1.5 h 3: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 4: sodium borohydride / methanol / 0.75 h / 0 °C 5: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

2-(3,4-bis (phenylmethoxy)phenyl)ethylamine hydrochloride (1699-56-5) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydrogen carbonate / CH2Cl2; H2O / 1.5 h 2: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 3: sodium borohydride / methanol / 0.75 h / 0 °C 4: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

N-(3,4-dibenzyloxyphenethyl)-4-benzyloxyphenylacetamide (23428-48-0) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: phosphorus oxychloride / acetonitrile / 0.42 h / Heating 2: sodium borohydride / methanol / 0.75 h / 0 °C 3: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

6,7-bisbenzyloxy-1-(4-benzyloxybenzyl)-3,4-dihydroisoquinoline hydrochloride (23428-49-1) → 6,7-dihydroxy-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (11041-94-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium borohydride / methanol / 0.75 h / 0 °C 2: hydrogen, conc. hydrochloric acid / 10percent palladium-charcoal / ethanol / 2 h View Scheme

Upstream product

• 1699-54-3 3,4-bis(benzyloxy)-β-nitrostyrene 
• 39188-62-0 2-(4-(benzyloxy)phenyl)acetyl chloride 
• 6547-53-1 2-[4-(benzyloxy)benzyl]acetic acid 
• 23428-49-1 6,7-bisbenzyloxy-1-(4-benzyloxybenzyl)-3,4-dihydroisoquinoline hydrochloride 
• 1699-56-5 2-(3,4-bis (phenylmethoxy)phenyl)ethylamine hydrochloride 
• 838-96-0 2-[4-(benzyloxy)phenyl]acetonitrile 
• 117765-29-4 6,7-bisbenzyloxy-1-(4-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride 
• 23428-48-0 N-(3,4-dibenzyloxyphenethyl)-4-benzyloxyphenylacetamide 

Relevant articles and documents

Biosynthesis. Part 24. Speculative Incorporation Experiments with 1-Benzylisoquinolines and a Logical Approach via C6-C2 and C6-C3 Precursors to the Biosynthesis of Hasubanonine and Protostephanine

Many possible 1-benzyltetrahydroisoquinolines have been examined as possible advanced precursors of the alkaloids hasubanonine (1) and protostephanine (2) in Stephania japonica plants, but none was incorporated significantly.Administration of various precursor molecules having only one aromatic ring, such as tyrosine, has demonstrated that both alkaloids are derived from two different C6-C2 biogenetic units.The subsequent failure of further 1-benzyltetrahydroisoquinolines and bisphenethylamines to be incorporated suggested the intermediacy of either (a) modified 1-benzylisoquinolines or (b) trioxygenated C6-C2 building blocks.Precursors designed to examine the first possibility, such as 1-benzyl-3,4-dihydroisoquinolines or 1-benzyl-1-carboxytetrahydroisoquinolines, were not incorporated into (1) and (2) whereas two 3',4',5'-trioxygenated 2-phenylethylamines were incorporated.These findings allow further delineation of the requirements for later precursors of the alkaloids (1) and (2).