4316-33-0

Basic information

• Product Name: 1-methoxy-4-(trimethoxymethyl)benzene
• Synonyms: 1-METHOXY-4-(TRIMETHOXYMETHYL)-BENZENE
• CAS NO: 4316-33-0
• Molecular Formula: C₁₁H₁₆O₄
• Molecular Weight: 212.2423
• Mol File: 4316-33-0.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 244.9°C at 760 mmHg
• Flash Point: 82.1°C
• Density: 1.065g/cm³
• Vapor Pressure: 0.0462mmHg at 25°C
• Refractive Index: 1.479
• CAS DataBase Reference: 1-methoxy-4-(trimethoxymethyl)benzene(CAS DataBase Reference)
• NIST Chemistry Reference: 1-methoxy-4-(trimethoxymethyl)benzene(4316-33-0)
• EPA Substance Registry System: 1-methoxy-4-(trimethoxymethyl)benzene(4316-33-0)

Safety Data

• Hazardous Substances Data: 4316-33-0(Hazardous Substances Data)

Usage

Synonym

Vanoxerine

Type of compound

Organic compound

Functional groups

One methoxy group and one trimethoxymethyl group

Usage

Dopamine transporter blocker

Potential treatment for

Cocaine addiction, attention deficit hyperactivity disorder (ADHD), and depression

Status

Not approved for medical use in most countries, classified as a controlled substance in the United States.

Synthetic route

methanol (67-56-1) + p-Anisaldehyde dimethyl acetal (2186-92-7) → p-Methoxybenzoic acid methyl orthoester (4316-33-0) + methyl 4-methoxybenzoate (121-98-2)

Conditions	Yield
With sodium methylate; lithium perchlorate; Tris(2,4-dibromophenyl)amine In dichloromethane indirect electrochemical oxidation;	A 78.3% B 13.2%
With sodium methylate; potassium benzenesulfonate; Tris(2,4-dibromophenyl)amine	A 53% B 18.4%

C10H12OS2(1+)*ClO4(1-) → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
With silver nitrate; triethylamine In methanol; acetonitrile for 10h; Ambient temperature;	53%

methyl (4-methoxyphenyl)carbodithioate (5874-09-9) + dibutyldimethoxytin (1067-55-6) → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

methanol (67-56-1) + Estragole (140-67-0) → p-Methoxybenzoic acid methyl orthoester (4316-33-0) + 1-(1,1-Dimethoxy-allyl)-4-methoxy-benzene (126501-50-6)

Conditions	Yield
With sodium methylate at 30℃; for 0.5h; electrolysis;	A 3 % Chromat. B 34 % Chromat.

methanol (67-56-1) + [Dimethoxy-(4-methoxy-phenyl)-methyl]-methyl-phenyl-amine (79431-14-4) → p-Methoxybenzoic acid methyl orthoester (4316-33-0) + N-methylaniline (100-61-8)

Conditions	Yield
With acetic acid for 0.166667h; Yield given;

methanol (67-56-1) + anethole (104-46-1) → p-Anisaldehyde dimethyl acetal (2186-92-7) + p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
With sodium 2,2,2-trifluoroacetate electrooxidation: current 0.8 A, current density 150 mA/cm2, 5F/mole;	A 76 % Chromat. B 11 % Chromat.

methanol (67-56-1) + anethole (104-46-1) → p-Anisaldehyde dimethyl acetal (2186-92-7) + p-Methoxybenzoic acid methyl orthoester (4316-33-0) + 1-(1,2-Dimethoxy-propyl)-4-methoxy-benzene (126501-48-2, 126501-49-3, 138169-72-9) + 1-(1,2-Dimethoxy-propyl)-4-methoxy-benzene (126501-48-2, 126501-49-3, 138169-72-9)

Conditions	Yield
With sodium methylate at 30℃; for 0.75h; Product distribution; electrolysis; other time, other alkenyl phenol ethers;

methanol (67-56-1) + anethole (104-46-1) → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
With sodium methylate at 30℃; for 0.75h; electrolysis;	11 % Chromat.

4-methoxy-N-methyl-N-phenylbenzamide. (33672-81-0) → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
Multi-step reaction with 3 steps 2: 1.) sodium / 1.) - 2.) CH2Cl2, 30 min 3: glacial acetic acid / 0.17 h View Scheme

Trifluoro-methanesulfonate[1-methoxy-1-(4-methoxy-phenyl)-meth-(Z)-ylidene]-methyl-phenyl-ammonium; → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) sodium / 1.) - 2.) CH2Cl2, 30 min 2: glacial acetic acid / 0.17 h View Scheme

methanol (67-56-1) + p-Anisaldehyde dimethyl acetal (2186-92-7) → p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
With potassium fluoride Electrochemical reaction; Continuous flow conditions;

methanol (67-56-1) + 4-methoxy-N-methyl-N-phenylbenzamide. (33672-81-0) + methyl trifluoromethanesulfonate (333-27-7) → p-Methoxybenzoic acid methyl orthoester (4316-33-0) + N-methylaniline (100-61-8)

Conditions	Yield
Stage #1: 4-methoxy-N-methyl-N-phenylbenzamide.; methyl trifluoromethanesulfonate In dichloromethane at 20℃; Stage #2: methanol With sodium In dichloromethane for 0.166667h; Overall yield = 4.35 g; Further stages;

p-Methoxybenzoic acid methyl orthoester (4316-33-0) + threothymidine (16053-52-4) → (R)-1-[2-deoxy-3,5-O-(4-methoxy-methoxybenzylidene)-β-D-threo-pentofuranosyl]thymine

Conditions	Yield
With pyridinium p-toluenesulfonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	70%

p-Methoxybenzoic acid methyl orthoester (4316-33-0) + cis,cis-1,3,5-trihydroxycyclohexane (50409-12-6) → 3-(4-methoxyphenyl)-2,4,10-trioxaadamantane

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane at 20℃; Inert atmosphere;	58%

t-butoxycarbonylhydrazine (870-46-2) + p-Methoxybenzoic acid methyl orthoester (4316-33-0) → N'-[(tert-Butoxycarbonyl-hydrazono)-(4-methoxy-phenyl)-methyl]-hydrazinecarboxylic acid tert-butyl ester (137256-74-7)

Conditions	Yield
With toluene-4-sulfonic acid a) r.t., 16 h, b) reflux, 6 h;	54%

p-Methoxybenzoic acid methyl orthoester (4316-33-0) + 1,3,3-trimethyl-2-oxa-bicyclo[2.2.2]octane-5,6-dione 6-hydrazone 5-oxime (68430-14-8, 72121-06-3, 139628-84-5) → 3-(4-methoxy-phenyl)-6,6,8-trimethyl-5,8-dihydro-6H-5,8-ethano-pyrano[4,3-e][1,2,4]triazine (73083-57-5)

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → methyl 4-methoxybenzoate (121-98-2)

Conditions	Yield
With water In acetonitrile at 30℃; Rate constant; ionic strength 0.50 M;

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → methanol (67-56-1) + 4-methoxybenzoic acid (100-09-4)

Conditions	Yield
With hydrogenchloride; potassium chloride In acetonitrile at 30℃; Rate constant; also in biphosphate buffer solution; kinetic isotope effect;

p-Methoxybenzoic acid methyl orthoester (4316-33-0) + 2-amino-5-(3-tert-butyl-4,4-dimethyl-4,5-dihydro-furan-2-yl)-3-methoxy-phenol → 6-(3-tert-butyl-4,4-dimethyl-4,5-dihydro-furan-2-yl)-4-methoxy-2-(4-methoxy-phenyl)-benzooxazole

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 6-(3-tert-butyl-4,4-dimethyl-4,5-dihydro-furan-2-yl)-2-(4-methoxy-phenyl)-benzooxazol-4-ol (244124-51-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: EtSNa / dimethylformamide View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 6-(5-tert-butyl-4,4-dimethyl-2,6,7-trioxa-bicyclo[3.2.0]hept-1-yl)-2-(4-methoxy-phenyl)-benzooxazol-4-ol

Conditions	Yield
Multi-step reaction with 3 steps 1: EtSNa / dimethylformamide 2: 93.2 percent / tetraphenylporphin; O2 / CH2Cl2 / 0.67 h / 0 °C / Irradiation View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 4-Amino-3-(4-methoxy-phenyl)-4H-[1,2,4]triazin-5-one (137257-07-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 54 percent / p-TsOH / a) r.t., 16 h, b) reflux, 6 h 2: 78 percent / conc. aq. HCl / methanol / 0.5 h / Ambient temperature 3: 49 percent / Et3N / methanol / 15 h / Ambient temperature View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 4-Amino-3-(4-methoxy-phenyl)-6-methyl-4H-[1,2,4]triazin-5-one (137257-10-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 54 percent / p-TsOH / a) r.t., 16 h, b) reflux, 6 h 2: 78 percent / conc. aq. HCl / methanol / 0.5 h / Ambient temperature 3: 55 percent / Et3N / methanol / 2 h / Heating View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 4-Amino-3-(4-methoxy-phenyl)-5-oxo-4,5-dihydro-[1,2,4]triazine-6-carboxylic acid methyl ester (137257-13-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 54 percent / p-TsOH / a) r.t., 16 h, b) reflux, 6 h 2: 78 percent / conc. aq. HCl / methanol / 0.5 h / Ambient temperature 3: 87 percent / Et3N / methanol / 24 h / Ambient temperature View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → C8H12N4O*2ClH

Conditions	Yield
Multi-step reaction with 2 steps 1: 54 percent / p-TsOH / a) r.t., 16 h, b) reflux, 6 h 2: 78 percent / conc. aq. HCl / methanol / 0.5 h / Ambient temperature View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridinium p-toluenesulfonate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2: acetonitrile / -40 - 0 °C / Inert atmosphere View Scheme

→ (S)-1-[2-deoxy-3,5-O-(4-methoxy-phosphonobenzylidene)-β-D-threo-pentofuranosyl]thymine disodium salt

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium p-toluenesulfonate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2.1: acetonitrile / -40 - 0 °C / Inert atmosphere 3.1: trimethylsilyl bromide; 2,6-dimethylpyridine / acetonitrile / 20 °C / Inert atmosphere 3.2: Dowex resin 50 Na+ form / Inert atmosphere View Scheme

p-Methoxybenzoic acid methyl orthoester (4316-33-0) → 3-(p-methoxyphenyl)-2,4-dioxabicyclo[3.3.1]nonan-7-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / dichloromethane / 20 °C / Inert atmosphere 2: borane-THF; N,N,N,N,N,N-hexamethylphosphoric triamide / tetrahydrofuran / 0 °C / Inert atmosphere View Scheme

Upstream product

• 67-56-1 methanol 
• 33672-81-0 4-methoxy-N-methyl-N-phenylbenzamide. 
• 333-27-7 methyl trifluoromethanesulfonate 
• 2186-92-7 p-Anisaldehyde dimethyl acetal 
• 104-46-1 anethole 
• 79431-14-4 [Dimethoxy-(4-methoxy-phenyl)-methyl]-methyl-phenyl-amine 
• 140-67-0 Estragole 
• 5874-09-9 methyl (4-methoxyphenyl)carbodithioate 
• 1067-55-6 dibutyldimethoxytin 

Downstream Products

• 137256-70-3 C₈H₁₂N₄O*2ClH 
• 137257-13-7 4-Amino-3-(4-methoxy-phenyl)-5-oxo-4,5-dihydro-[1,2,4]triazine-6-carboxylic acid methyl ester 
• 137257-10-4 4-Amino-3-(4-methoxy-phenyl)-6-methyl-4H-[1,2,4]triazin-5-one 
• 137257-07-9 4-Amino-3-(4-methoxy-phenyl)-4H-[1,2,4]triazin-5-one 
• 244124-51-4 6-(3-tert-butyl-4,4-dimethyl-4,5-dihydro-furan-2-yl)-2-(4-methoxy-phenyl)-benzooxazol-4-ol 
• 67-56-1 methanol 
• 100-09-4 4-methoxybenzoic acid 
• 121-98-2 methyl 4-methoxybenzoate 
• 137256-74-7 N'-[(tert-Butoxycarbonyl-hydrazono)-(4-methoxy-phenyl)-methyl]-hydrazinecarboxylic acid tert-butyl ester 
• 73083-57-5 3-(4-methoxy-phenyl)-6,6,8-trimethyl-5,8-dihydro-6H-5,8-ethano-pyrano[4,3-e][1,2,4]triazine 

Relevant articles and documents

Enantioselective Desymmetrization of cis-3,5- O-Arylidenecyclohexanones Catalyzed by Cinchona-Derived Quaternary Ammonium Salts

An enantioselective protocol for the desymmetrization of cis-3,5-O-arylidenecyclohexanones has been developed that proceeded under the catalysis of readily available and inexpensive Cinchona-derived quaternary ammonium salts. The synthetic relevance of the methodology was exemplified by the synthesis of a key intermediate that could be used in the preparation of the active pharmaceutical ingredient, paricalcitol (Zemplar).

ELECTROCHEMICAL CLEAVAGE OF THE DOUBLE BOND OF 1-ALKENYLARENES

A study has been made of the electrochemical cleavage of the double bond of propenylbenzene (Ia) and p-propenylanisole (Ib), which takes place upon anodic oxidation of (Ia, b) in alcoholic solutions of sodium trifluoroacetate and other electrolytes and which leads to conversion of (Ia, b) to benzaldehyde dialkylacetals.Conditions are found that provide for highly selective (>80percent) conversion of (Ib) and p-propenyltoluene to p-methyl- and p-methoxybenzaldehyde dimethylacetals.

Isolation of Dithiolanylium Salts and Their Conversion to Ketene Dithioacetals and Ortho Esters

Various 2-substituted 1,3-dithiolan-2-ylium perchlorates (1) were prepared by the reaction of 1,2-ethanedithiol with acyl chlorides in the presence of perchloric acid.Treatments of 1 with triethylamine gave 2-alkylidene-1,3-dithiolane (2) when the 2-substituent was a primary or secondary alkyl group. 2-Aryl derivatives of 1 were converted to ortho esters by the reaction with methanol in the presence of silver nitrate. 1,3-Dithian-2-ylium perchlorates and 2-alkylidene-1,3-dithianes were also prepared similarly from 1,3-propanedithiol.