18559-59-6

Basic information

• Product Name: (S)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride
• Synonyms: (S)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride;TRETOQUINOLHCL;(-)-Trimethoquinol;6,7-Isoquinolinediol, 1,2,3,4-tetrahydro-1-[(3,4,5-trimethoxyphenyl)methyl]-, hydrochloride, (1S)- (9CI);6,7-Isoquinolinediol, 1,2,3,4-tetrahydro-1-[(3,4,5-trimethoxyphenyl)methyl]-, hydrochloride, (S)-;AQL 208;Bentomex;Inolin
• CAS NO: 18559-59-6
• Molecular Formula: C₁₉H₂₃NO₅*ClH
• Molecular Weight: 381.85056
• EINECS: 242-423-5
• Product Categories: Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 18559-59-6.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 533.3°Cat760mmHg
• Flash Point: 276.3°C
• Appearance: /
• Density: 1.235g/cm³
• Vapor Pressure: 6.29E-13mmHg at 25°C
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: (S)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride(18559-59-6)
• EPA Substance Registry System: (S)-1,2,3,4-tetrahydro-6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)isoquinolinium chloride(18559-59-6)

Safety Data

• Hazardous Substances Data: 18559-59-6(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 18559-59-6 differently. You can refer to the following data:
1. S-(-)
2. S-(-)-Tretoquinol belongs to the class of adrenergic inhalants, selective β-2-adrenoreceptor agonists. S-(-)-Tretoquinol is used in the treatment of obstructive airway diseases. S-(-)-Tretoquinol is a bronchodilator.

InChI:InChI=1/C19H23NO5.ClH/c1-23-17-7-11(8-18(24-2)19(17)25-3)6-14-13-10-16(22)15(21)9-12(13)4-5-20-14;/h7-10,14,20-22H,4-6H2,1-3H3;1H/t14-;/m0./s1

Synthetic route

(S)-6,7-Bis(benzyloxy)-1-<(3,4,5-trimethoxyphenyl)methyl>-1,2,3,4-tetrahydroisoquinoline hydrochloride → (-)-Trimetoquinol hydrochloride (18559-59-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol at 50℃; under 3040 Torr; for 16h;	96%

(1S,1'S)-6,7-dibenzyloxy-2-(2-hydroxy-1-phenylethyl)-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline → (-)-Trimetoquinol hydrochloride (18559-59-6)

Conditions	Yield
With hydrogenchloride; hydrogen; palladium on activated charcoal In ethanol	86%

(3S)-8,9-dibenzyloxy-3-phenyl-2,3,5,6-tetrahydro-10bH-oxazolo-<2,3-a>isoquinoline → (-)-Trimetoquinol hydrochloride (18559-59-6)

Conditions	Yield
Multi-step reaction with 2 steps 2: 86 percent / H2, 10percent HCl / 10percent Pd-C / ethanol View Scheme

5-(chloromethyl)-1,2,3-trimethoxybenzene (3840-30-0) → (-)-Trimetoquinol hydrochloride (18559-59-6)

Conditions	Yield
Multi-step reaction with 2 steps 2: 86 percent / H2, 10percent HCl / 10percent Pd-C / ethanol View Scheme

N-(2-nitrophenylsulfenyl)-β-(3-hydroxy-4-(methoxymethoxy)phenyl)ethylamine → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: magnesium sulfate; (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid; (S)-[1,1']-binaphthalenyl-2,2'-diol / toluene / 80 °C / Inert atmosphere 2: hydrogenchloride / ethanol; water; dichloromethane / 24 h / 20 °C View Scheme

3-hydroxy-4-(methoxymethoxy)benzaldehyde (65299-00-5) → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions

Yield

Multi-step reaction with 5 steps 1: ammonium acetate / 1 h / Molecular sieve; Reflux 2: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere; Reflux 3: triethylamine; potassium carbonate / water; chloroform; methanol / 2 h / 0 °C 4: magnesium sulfate; (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid; (S)-[1,1']-binaphthalenyl-2,2'-diol / toluene / 80 °C / Inert atmosphere 5: hydrogenchloride / ethanol; water; dichloromethane / 24 h / 20 °C View Scheme

3,4-dihydroxybenzaldehyde (139-85-5) → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions

Yield

Multi-step reaction with 6 steps 1.1: potassium carbonate / acetonitrile / 0.5 h / 20 °C 1.2: 2 h 2.1: ammonium acetate / 1 h / Molecular sieve; Reflux 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere; Reflux 4.1: triethylamine; potassium carbonate / water; chloroform; methanol / 2 h / 0 °C 5.1: magnesium sulfate; (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid; (S)-[1,1']-binaphthalenyl-2,2'-diol / toluene / 80 °C / Inert atmosphere 6.1: hydrogenchloride / ethanol; water; dichloromethane / 24 h / 20 °C View Scheme

C27H30N2O8S → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions	Yield
With hydrogenchloride In ethanol; dichloromethane; water at 20℃; for 24h; Overall yield = 86 %; Overall yield = 62 mg;

(E)-3-hydroxy-4-(methoxymethoxy)-1-(2-nitrovinyl)benzene → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions

Yield

Multi-step reaction with 4 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 3 h / 0 °C / Inert atmosphere; Reflux 2: triethylamine; potassium carbonate / water; chloroform; methanol / 2 h / 0 °C 3: magnesium sulfate; (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid; (S)-[1,1']-binaphthalenyl-2,2'-diol / toluene / 80 °C / Inert atmosphere 4: hydrogenchloride / ethanol; water; dichloromethane / 24 h / 20 °C View Scheme

β-(3-hydroxy-4-(methoxymethoxy)phenyl)ethylamine → (-)-Trimetoquinol hydrochloride (18559-59-6) + (+)-Trimetoquinol hydrochloride

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine; potassium carbonate / water; chloroform; methanol / 2 h / 0 °C 2: magnesium sulfate; (R)-3,3'-bis(2,4,6-triisopropylphenyl)binol phosphoric acid; (S)-[1,1']-binaphthalenyl-2,2'-diol / toluene / 80 °C / Inert atmosphere 3: hydrogenchloride / ethanol; water; dichloromethane / 24 h / 20 °C View Scheme

Upstream product

• 139-85-5 3,4-dihydroxybenzaldehyde 
• 65299-00-5 3-hydroxy-4-(methoxymethoxy)benzaldehyde 
• 3840-30-0 5-(chloromethyl)-1,2,3-trimethoxybenzene 

Relevant articles and documents

Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids

(Figure Presented) A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.

Asymmetric synthesis of 1-benzyltetrahydroisoquinolines using chiral oxazolo[2,3-a]tetrahydroisoquinolines

A novel synthetic route to enantiomerically pure 1-benzyltetrahydroisoquinolines (1) was developed via the reaction of oxazolo[2,3-a]tetrahydroisoquinoline (5) with benzyltriisopropoxytitanium compounds (10). This method was applied to the synthesis of (S)-trimetoquinol (1c; a bronchodilator).