621-59-0

Basic information

• Product Name: Isovanillin
• Synonyms: ISOVANILIN;ISOVANILLIN;4-METHOXY-3-HYDROXYBENZALDEHYDE;3-HYDROXY-4-ANISALDEHYDE;3-HYDROXY-4-METHOXYBENZALDEHYDE;3-HYDROXYANISALDEHYDE;3-HYDROXY-P-ANISALDEHYDE;AKOS B022473
• CAS NO: 621-59-0
• Molecular Formula: C₈H₈O₃
• Molecular Weight: 152.15
• EINECS: 210-694-9
• Product Categories: FINE Chemical & INTERMEDIATES;Aromatic Aldehydes & Derivatives (substituted);BenzaldehydeDerivative;Benzaldehyde;Aromatics;Matrix Substances for MALDI-MS;Aldehydes;Analytical Reagents;Analytical/Chromatography;Building Blocks;C8;Carbonyl Compounds;Chemical Synthesis;Mass Spectrometry;Mass Spectrometry (MS);Matrices for MALDI Analysis;Organic Building Blocks;Proteomics;Spectroscopy;Piperidines ,Piperazines ,Homopiperidines
• Mol File: 621-59-0.mol
• Article Data: 84

Chemical Properties

• Melting Point: 113-116 °C
• Boiling Point: 179 °C15 mm Hg(lit.)
• Flash Point: 179°C/15mm
• Appearance: faintly brown/crystalline
• Density: 1.20
• Vapor Pressure: 0.000384mmHg at 25°C
• Refractive Index: 1.4945 (estimate)
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Soluble in acetone and methanol.
• PKA: pK1:8.889 (25°C)
• Water Solubility: 2.27g/L at 20℃
• Sensitive: Air Sensitive
• BRN: 1073021
• CAS DataBase Reference: Isovanillin(CAS DataBase Reference)
• NIST Chemistry Reference: Isovanillin(621-59-0)
• EPA Substance Registry System: Isovanillin(621-59-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37-36
• WGK Germany: 3
• RTECS: CU6540000
• TSCA: Yes
• Hazardous Substances Data: 621-59-0(Hazardous Substances Data)

Usage

Chemical Properties

Light Tan Cyrstalline Solid

Uses

3-Hydroxy-4-methoxybenzaldehyde was used as starting reagent during the two-step stereoselective synthesis of the anticancer drug (Z)-combretastatin A-4 and glycitein synthesis.

Application

Isovanillin is a kind of fragrance and isomer of vanillin. it has unique properties than vanillin, its fragrance can change with the change of ambient temperature, so it is especially suitable for special cosmetics and some special fragrance industries. Isovanillin is a selective inhibitor of aldehyde oxidase. It is not a substrate of that enzyme, and is metabolized by aldehyde dehydrogenase into isovanillic acid, which could make it a candidate drug for use in alcohol aversion therapy.

Preparation

Synthesis of isovanillin: 4-Hydroxybenzaldehyde is used as raw material, firstly react with bromine to obtain 3-bromo-4-hydroxybenzaldehyde, then react with methyl iodide to obtain 3-bromo-4-methoxybenzaldehyde, and then hydrolyzed under the action of sodium hydroxide and cuprous chloride to produce isovanillin. The yield was 64.1%.

Synthesis Reference(s)

The Journal of Organic Chemistry, 45, p. 1596, 1980 DOI: 10.1021/jo01297a010

General Description

3-Hydroxy-4-methoxybenzaldehyde on condensation with furan-2-carboxylic acid hydrazide and thiophene-2-carboxylic acid hydrazide yields Schiff-bases. It undergoes condensation reaction with1-azabicyclo[2.2.2]octan-3-one to give (Z)-2-(3-hydroxy-4-methoxybenzylidene)-1-azabicyclo[2.2.2]octan-3-one.

Flammability and Explosibility

Notclassified

Purification Methods

Crystallise isovaniline from H2O or *C6H6. The oxime has m 147o. [Beilstein 8 IV 1764.]

InChI:InChI=1/C8H8O3/c1-11-8-3-2-6(5-9)4-7(8)10/h2-5,10H,1H3

Synthetic route

3-hydroxy-4-methoxybenzyl alcohol (4383-06-6) → isovanillin (621-59-0)

Conditions	Yield
With silica gel; 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium perchlorate In dichloromethane	100%
With oxygen In toluene at 80℃; under 760.051 Torr; for 24h;	99%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane for 16h; Ambient temperature;	97%

4-methoxy-5-methoxycarbonyloxy-2-methylbenzaldehyde (132638-47-2) → isovanillin (621-59-0)

Conditions	Yield
With sodium hydroxide Ambient temperature;	100%

3-benzyloxy-4-methoxybenzaldehyde (6346-05-0) → isovanillin (621-59-0)

Conditions	Yield
With iron(III) chloride on silica In neat (no solvent) at 30℃; for 1h;	99%
With sodium hydrogen sulfate; silica gel; methoxybenzene at 115℃; for 3h;	87%
With magnesium iodide for 10h; neat (no solvent);	87%
With sulfosuccinic acid functionalized mesoporous silica In ethanol at 100℃;

O-methoxymethylisovanillin (5779-98-6) → isovanillin (621-59-0)

Conditions	Yield
With β‐cyclodextrin In water at 60℃; for 0.15h; Microwave irradiation;	99%
H6P2W18O62; silica gel In tetrahydrofuran; methanol at 65℃; for 1h;	95%
With ytterbium(III) chloride In neat (no solvent) at 70 - 120℃; for 0.0333333h; Microwave irradiation; Green chemistry;	95%

4-methoxy-3-(tetrahydro-2H-pyran-2-yloxy)benzaldehyde (106852-87-3) → isovanillin (621-59-0)

Conditions	Yield
With β‐cyclodextrin In water at 60℃; for 0.15h; Microwave irradiation;	99%
With ytterbium(III) chloride In neat (no solvent) at 70 - 120℃; for 0.0333333h; Microwave irradiation; Green chemistry;	94%

isovanillin acetate (881-57-2) → isovanillin (621-59-0)

Conditions	Yield
With β‐cyclodextrin In water at 60℃; for 0.15h; Microwave irradiation;	99%
With ytterbium(III) chloride In neat (no solvent) at 70 - 120℃; for 0.0333333h; Microwave irradiation; Green chemistry;	98%

C15H16N2O4S → isovanillin (621-59-0)

Conditions	Yield
With water; phosphorus pentoxide for 0.00861111h; microwave irradiation;	98%
With phosphoric acid for 0.00833333h; microwave irradiation;	68%

Sodium; hydroxy-(3-hydroxy-4-methoxy-phenyl)-methanesulfonate → isovanillin (621-59-0)

Conditions	Yield
With Montmorillonite KSF clay for 0.00277778h; Elimination; microwave irradiation;	96%
With ammonium acetate for 0.0105556h; microwave irradiation;	93%

5-formyl-2-methoxyphenyl 4-methylbenzenesulfonate (78515-24-9) → isovanillin (621-59-0)

Conditions	Yield
With ytterbium(III) chloride In neat (no solvent) at 70 - 120℃; for 0.0333333h; Microwave irradiation; Green chemistry;	96%
With β‐cyclodextrin In water at 60℃; for 0.15h; Microwave irradiation;	70%

dimethyl sulfate (77-78-1) + 3,4-dihydroxybenzaldehyde (139-85-5) → isovanillin (621-59-0) + vanillin (121-33-5)

Conditions	Yield
With sodium hydroxide In dichloromethane; water at 55 - 60℃; for 1.58333h;	A 93.5% B 5.8%
With MES buffer In ethanol; water at 37℃; Kinetics; Thermodynamic data; O-methylation in the absence or in the presence of metal ion, ΔH(excit.), ΔS(excit.);
With HCl methanol buffer; BIS-TRIS at 37℃; Rate constant; Thermodynamic data; Kinetics; other divalent metal ions catalysts, var. temperat.; Ea, ΔH(excit.), ΔS(excit.);
With sodium hydroxide In dichloromethane; water at 55 - 60℃; for 5h;	A 8 %Chromat. B 77.5 %Chromat.

3-hydroxy-4-methoxybenzyl bromide (111394-51-5) → isovanillin (621-59-0)

Conditions	Yield
With water; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 50℃; for 0.916667h; Ionic liquid; Inert atmosphere;	92%
With trihexyl (tetradecyl) phosphonium tetrafluoroborate; dihydrogen peroxide In water at 50℃; for 0.833333h; Inert atmosphere;	88%

Conditions	Yield
With aluminum (III) chloride In toluene at 20℃; for 8h;	92%
With aluminum (III) chloride In dichloromethane at 20℃; for 5h;	41.4%

Conditions	Yield
With iodine In dimethyl sulfoxide at 130℃; for 0.5h;	91%
With potassium hydroxide; palladium on activated charcoal In methanol at 20℃; for 4h;	87%
With potassium hydroxide In methanol at 20℃; for 5h;	87%

5-(Dimethyl-hydrazonomethyl)-2-methoxy-phenol (59670-58-5) → isovanillin (621-59-0)

Conditions	Yield
With chloro-trimethyl-silane; sodium iodide In water; acetonitrile for 0.05h; deprotection;	88%

p-methoxy-m-(tert-butyldimethylsilyloxy)-benzaldehyde (97315-18-9) → isovanillin (621-59-0)

Conditions	Yield
With tin(ll) chloride In ethanol at 20℃; for 5h;	85%
With potassium-exchanged zirconium hydrogen phosphate In water; acetone at 60℃; for 8h; desilylation;	83%

3-benzyloxy-4-methoxybenzaldehyde (6346-05-0) → 2-benzyl-3-hydroxy-4-methoxybenzaldehyde + 2-benzyl-4-methoxy-5-hydroxybenzaldehyde + isovanillin (621-59-0)

Conditions	Yield
With methanol; amberlyst-15 In toluene at 110℃;	A n/a B n/a C 83%

3,4-dihydroxybenzaldehyde (139-85-5) + methyl iodide (74-88-4) → isovanillin (621-59-0)

Conditions	Yield
With sodium chloride; ammonium chloride; lithium carbonate In N,N-dimethyl-formamide	82.2%
With potassium carbonate In N,N-dimethyl-formamide at 20 - 70℃; Inert atmosphere;	48%
With methanol; potassium hydroxide

2-bromoisovanillin (2973-58-2) → isovanillin (621-59-0)

Conditions	Yield
With potassium carbonate; isopropyl alcohol; palladium diacetate; triphenylphosphine at 90℃; for 14h;	82%

3,4-dimethoxy-benzaldehyde (120-14-9) → isovanillin (621-59-0) + vanillin (121-33-5) + 3,4-dihydroxybenzaldehyde (139-85-5)

Conditions	Yield
With orcinol; Acetobacterium dehalogenans veratrol-O-demethylase; Desulfitobacterium hafniense methyltransferase dhaf4611 In aq. buffer at 35℃; for 24h; pH=6.5; Inert atmosphere; Enzymatic reaction; regioselective reaction;	A 11% B 81% C 8%
With lithium chloride In N,N-dimethyl-formamide for 22h; Heating; Yield given. Yields of byproduct given;

2-(3-hydroxy-4-methoxyphenyl)-1,3-dithian (110815-90-2) → isovanillin (621-59-0)

Conditions	Yield
With zirconium sulphenyl phosphonate; Glyoxilic acid at 60℃; for 1.5h;	81%

5-[1,3]Dithiolan-2-yl-2-methoxy-phenol → isovanillin (621-59-0)

Conditions	Yield
With zirconium sulphenyl phosphonate; Glyoxilic acid at 60℃; for 1.5h;	79%

3-hydroxy-4-methoxybenzaldehyde oxime → isovanillin (621-59-0)

Conditions	Yield
With water; phosphorus pentoxide for 0.0111111h; microwave irradiation;	79%
With dihydrogen phosphate for 0.0111111h; microwave irradiation;	75%
With CuCl2*2H2O for 0.0205556h; microwave irradiation;	73%

methanol (67-56-1) + 3,4-dihydroxybenzaldehyde (139-85-5) → isovanillin (621-59-0)

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Mitsunobu reaction; regioselective reaction;	76%

2-Methoxy-5-(phenyl-hydrazonomethyl)-phenol (59670-56-3) → isovanillin (621-59-0)

Conditions	Yield
With water; phosphorus pentoxide for 0.0194444h; microwave irradiation;	75%
With phosphoric acid for 0.0111111h; microwave irradiation;	72%

3-bromo-4-methoxybenzylaldehyde (34841-06-0) → isovanillin (621-59-0)

Conditions	Yield
With tetrabutylammomium bromide; copper(l) chloride; sodium hydroxide In water at 120℃; Reagent/catalyst; Temperature;	75%

3-hydroxy-4-methoxy-benzaldehyde-semicarbazone (115213-68-8) → isovanillin (621-59-0)

Conditions	Yield
With CuCl2*2H2O for 0.0205556h; microwave irradiation;	71%
With water; phosphorus pentoxide for 0.0194444h; microwave irradiation;	68%
With phosphoric acid for 0.0111111h; microwave irradiation;	56%

sodium methylate (124-41-4) + 6-bromo-3,4-methylenedioxybenzaldehyde (15930-53-7) → isovanillin (621-59-0) + 3-hydroxy-4,6-dimethoxybenzaldehyde (80832-63-9)

Conditions	Yield
With copper dichloride In N,N-dimethyl-formamide at 100 - 105℃; for 1.5h;	A 8% B 70%

6-bromo-3,4-methylenedioxybenzaldehyde (15930-53-7) → isovanillin (621-59-0) + 3-hydroxy-4,6-dimethoxybenzaldehyde (80832-63-9)

Conditions	Yield
With sodium methylate; copper dichloride In N,N-dimethyl-formamide at 100 - 105℃; for 1.5h;	A 8% B 70%

4-methoxy-benzaldehyde (123-11-5) → isovanillin (621-59-0)

Conditions	Yield
Stage #1: 4-methoxy-benzaldehyde With 6,7-dichlorobenzo[d][1,2]dioxine-1,4-dione at 75℃; Stage #2: With sodium hydrogencarbonate In methanol; water at 50℃;	69%

piperonal (120-57-0) → isovanillin (621-59-0)

Conditions	Yield
With sodium methylate In methanol; N,N,N,N,N,N-hexamethylphosphoric triamide at 150℃; for 0.15h;	62.6%
With copper dichloride In N,N-dimethyl-formamide at 100 - 105℃; for 1.5h;	62%
With sodium methylate In methanol; dimethyl sulfoxide at 150℃;

isovanillin (621-59-0) → 5-methyl-2-methoxyphenol (1195-09-1)

Conditions	Yield
With hydrazine hydrate; potassium hydroxide at 130 - 190℃; for 6h;	100%
With hydrazine hydrate; potassium hydroxide In ethylene glycol at 130 - 190℃; for 6h; Wolff-Kishner Reduction; Inert atmosphere;	99%
With palladium 10% on activated carbon; hydrogen In ethyl acetate under 5171.62 Torr; for 24h;	92%

isovanillin (621-59-0) + benzyl chloride (100-44-7) → 3-benzyloxy-4-methoxybenzaldehyde (6346-05-0)

Conditions	Yield
With potassium carbonate; sodium iodide In ethanol for 4.5h; Heating;	100%
With potassium carbonate In N,N-dimethyl-formamide at 50℃; benzylation;	100%
With potassium hydroxide In ethanol for 4.25h; Heating;	98%

isovanillin (621-59-0) + isopropyl bromide (75-26-3) → O-isopropylisovanillin (34123-66-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere;	100%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	100%
With potassium carbonate In dimethyl sulfoxide at 55℃; for 11h; Inert atmosphere;	100%

isovanillin (621-59-0) + benzyl bromide (100-39-0) → 3-benzyloxy-4-methoxybenzaldehyde (6346-05-0)

Conditions	Yield
With potassium carbonate In methanol for 4h; Reflux;	100%
With potassium carbonate In methanol for 4h; Reflux;	100%
With potassium carbonate In methanol for 2h; Reflux;	100%

isovanillin (621-59-0) + 2,4-bis(trifluoromethyl)benzyl bromide (140690-56-8) → 3-{[2,4-bis(trifluoromethyl)benzyl]oxy}-4-methoxybenzaldehyde (1264753-88-9)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 6h;	100%

isovanillin (621-59-0) + 2,4-bis(4’-methoxyphenylamino)-6-(4’-acetylphenylamino) s-triazine → C33H30N6O5 (1422249-88-4)

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide	100%

isovanillin (621-59-0) + anthranilic acid amide (28144-70-9) → 2-[3-hydroxy-4-(methyloxy)phenyl]quinazolin-4(3H)-one (1427578-66-2)

Conditions	Yield
With copper(II) choride dihydrate In ethanol for 16h; Reflux;	100%
With copper(II) choride dihydrate In ethanol for 16h; Reflux;	100%
Stage #1: anthranilic acid amide With sodium acetate In N,N-dimethyl-formamide for 0.166667h; Stage #2: isovanillin With iodine In N,N-dimethyl-formamide at 70 - 80℃; for 24h;	92.3%

isovanillin (621-59-0) + 3-acetylcoumarin (3949-36-8) → C19H14O5

Conditions	Yield
With potassium hydroxide In ethanol Reflux;	100%

isovanillin (621-59-0) → 3,4-dihydroxybenzaldehyde (139-85-5)

Conditions	Yield
Stage #1: isovanillin With pyridine; iodine; aluminium In acetonitrile for 18h; Reflux; Stage #2: With hydrogenchloride In water; acetonitrile at 20℃;	99%
With aluminium(III) iodide In dimethyl sulfoxide; acetonitrile at 80℃; for 18h;	95%
With aluminium(III) iodide; dimethyl sulfoxide In acetonitrile at 80℃; for 18h;	95%

isovanillin (621-59-0) + methanesulfonyl chloride (124-63-0) → 5-formyl-2-methoxyphenyl methanesulfonate (70205-05-9)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2h;	99%
With triethylamine In dichloromethane at 20℃; for 2h;	99%
With triethylamine In N,N-dimethyl-formamide at 0℃;	92%

isovanillin (621-59-0) + Cyclopentyl bromide (137-43-9) → 3-cyclopentyloxy-4-methoxybenzylaldehyde (67387-76-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 16h;	99%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; for 12h;	97%
With potassium carbonate In N,N-dimethyl-formamide at 100℃;	97%

isovanillin (621-59-0) + trifluoromethylsulfonic anhydride (358-23-6) → 4-methoxy-3-trifluoromethanesulfonyloxybenzaldehyde (157790-73-3)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃; for 14h; Inert atmosphere;	99%
With pyridine In dichloromethane at 0℃; for 0.25h;	91%
With N-ethyl-N,N-diisopropylamine In dichloromethane at -78 - 20℃; for 0.666667h;	85%
With pyridine In dichloromethane at 0℃; for 1.5h; Inert atmosphere;	75%

isovanillin (621-59-0) + triisopropylsilyl chloride (13154-24-0) → 4-methoxy-3-(triisopropylsilyloxy)-benzaldehyde (179260-96-9)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;	99%
With 1H-imidazole In N,N-dimethyl-formamide for 16h; Ambient temperature;	98%
With 1H-imidazole In dichloromethane at 0 - 20℃; Inert atmosphere;
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 3h; Inert atmosphere;	15.5 g

isovanillin (621-59-0) + allyl bromide (106-95-6) → O-allylisovanillin (18075-40-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 60℃;	99%
With potassium carbonate In acetone for 3h; Heating;	99%
With potassium carbonate In N,N-dimethyl-formamide at 60℃; Allylation;	99%

isovanillin (621-59-0) + 2-cyano-N-[6-(2-cyanoacetylamino)hexyl]acetamide (26889-89-4) → 2-cyano-N-{6-[2-cyano-3-(3-hydroxy-4-methoxyphenyl)-acryloylamino]hexyl}-3-(3-hydroxy-4-methoxyphenyl)acrylamide

Conditions	Yield
With piperidine In ethanol for 2h; Heating;	99%

isovanillin (621-59-0) + 1-iodo-propane (107-08-4) → 4-methoxy-3-propoxy-benzaldehyde (5922-56-5)

Conditions	Yield
With potassium carbonate; potassium iodide In butanone Reflux;	99%
With potassium carbonate In N,N-dimethyl-formamide
With potassium carbonate In N,N-dimethyl-formamide

isovanillin (621-59-0) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → ethyl (E)-3-(3-hydroxy-4-methoxyphenyl)-2-propenoate

Conditions	Yield
In toluene at 22 - 25℃; for 8h; Wittig reaction;	99%

Upstream product

• 74-83-9 methyl bromide 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 74-88-4 methyl iodide 
• 120-57-0 piperonal 
• 124-41-4 sodium methylate 
• 15930-53-7 6-bromo-3,4-methylenedioxybenzaldehyde 
• 7446-70-0 aluminium trichloride 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 519-05-1 opianic acid 
• 2973-58-2 2-bromoisovanillin 
• 121-33-5 vanillin 
• 34127-96-3 3-butyloxy-4-methoxybenzaldehyde 
• 34123-66-5 O-isopropylisovanillin 
• 5922-56-5 4-methoxy-3-propoxy-benzaldehyde 

Downstream Products

• 101732-58-5 2-((Z)-3-hydroxy-4-methoxy-benzylidene)-4,6-dimethoxy-benzofuran-3-one 
• 3207-31-6 3-(3-acetoxy-4-methoxyphenyl)acrylic acid 
• 881-57-2 isovanillin acetate 
• 71155-68-5 3-Acetoxy-4-methoxy-1-(diacetoxymethyl)benzene 
• 5779-98-6 O-methoxymethylisovanillin 
• 19784-98-6 Isochavibetol 
• 39816-35-8 (E)-2-methoxy-5-(2'-nitrovinyl)phenol 
• 63223-54-1 2-(3-hydroxy-4-methoxy-phenyl)-2,3-dihydro-benzo[e][1,3]thiazin-4-one 
• 129803-26-5 3-Hydroxy-4-methoxy-α-cyanobenzyl Benzoate 
• 6346-05-0 3-benzyloxy-4-methoxybenzaldehyde 
• 23428-77-5 1‐(3‐(benzyloxy)‐4‐methoxyphenyl)ethanone 
• 89607-58-9 2-(3-hydroxy-4-methoxyphenyl)-1,1-dicyanoethylene 
• 19646-36-7 2-Methoxy-5-((E)-pent-1-enyl)-phenol 
• 33617-54-8 3-trimethylsilylether-4-methoxybenzaldehyde 

Relevant articles and documents

One-Pot Biocatalytic In Vivo Methylation-Hydroamination of Bioderived Lignin Monomers to Generate a Key Precursor to L-DOPA

Electron-rich phenolic substrates can be derived from the depolymerisation of lignin feedstocks. Direct biotransformations of the hydroxycinnamic acid monomers obtained can be exploited to produce high-value chemicals, such as α-amino acids, however the reaction is often hampered by the chemical autooxidation in alkaline or harsh reaction media. Regioselective O-methyltransferases (OMTs) are ubiquitous enzymes in natural secondary metabolic pathways utilising an expensive co-substrate S-adenosyl-l-methionine (SAM) as the methylating reagent altering the physicochemical properties of the hydroxycinnamic acids. In this study, we engineered an OMT to accept a variety of electron-rich phenolic substrates, modified a commercial E. coli strain BL21 (DE3) to regenerate SAM in vivo, and combined it with an engineered ammonia lyase to partake in a one-pot, two whole cell enzyme cascade to produce the l-DOPA precursor l-veratrylglycine from lignin-derived ferulic acid.

Method for synthesizing isovanillin

The invention provides a method for synthesizing isovanillin, and belongs to the technical field of chemical engineering. The method for synthesizing isovanillin comprises the steps of (1) conducting a methylation reaction, specifically, adding ethyl vanillin, dimethyl sulfoxide, Pd (OAc) 2 and a sodium hydroxide solution into a reaction kettle, carrying out oxygen replacement, controlling the oxygen pressure at 0.2 MPa, reacting at the temperature of 100 DEG C for 6 hours, ending the reaction, and filtering and separating the reaction liquid to obtain an oil-phase intermediate; (2) conducting a hydrolysis reaction, specifically, adding the oil-phase intermediate, a SO4/ZrOTiO2 catalyst and water into the reaction kettle, reacting at the temperature of 65 DEG C, and ending the reaction; carrying out suction filtration on the reaction liquid, dissolving a filter cake with 2000g of ethanol, carrying out heat preservation stirring at the temperature of 60 DEG C for 2-6 hours, and carrying out suction filtration; cooling the filtrate to 0 DEG C, preserving heat and stirring for 2-6 hours, and performing suction filtration to obtain a wet product; and drying the obtained solid in vacuum until the weight is constant to obtain the isovanillin.

Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol- O-demethylase

The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol-O-demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac-yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products.