93-02-7

Basic information

• Product Name: 2,5-Dimethoxybenzaldehyde
• Synonyms: 2,5-dimethoxy-benzaldehyd;2,5-DIMETHOXYBENZALDEHYDE;AKOS BBS-00003162;Benzaldehyde, 2,5-dimethoxy-;2,5-Dimethoxybenzaldehyde, 98+%;2,5-Dimethoxybenzaldehyde,97%;2,5-Dimethoxybenzald;5-DiMethoxy benzaldehyde
• CAS NO: 93-02-7
• Molecular Formula: C₉H₁₀O₃
• Molecular Weight: 166.17
• EINECS: 202-211-5
• Product Categories: FINE Chemical & INTERMEDIATES;BUILDING BLOCKS;Benzaldehyde;Adehydes, Acetals & Ketones;Anisoles, Alkyloxy Compounds & Phenylacetates;Aldehydes;C9;Carbonyl Compounds;Aromatics;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks
• Mol File: 93-02-7.mol
• Article Data: 87

Chemical Properties

• Melting Point: 46-48 °C(lit.)
• Boiling Point: 146 °C10 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Yellow to beige/Crystalline Powder, Crystals and/or Chunks
• Density: 1.1708 (rough estimate)
• Refractive Index: 1.5260 (estimate)
• Storage Temp.: Refrigerator
• Solubility: 795mg/l
• Water Solubility: Soluble in chloroform and methanol. Slightly soluble in water.
• Sensitive: Air Sensitive
• BRN: 509301
• CAS DataBase Reference: 2,5-Dimethoxybenzaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 2,5-Dimethoxybenzaldehyde(93-02-7)
• EPA Substance Registry System: 2,5-Dimethoxybenzaldehyde(93-02-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-43
• Safety Statements: 26-36/37/39-24/25-36
• WGK Germany: 2
• RTECS: CU5740500
• TSCA: Yes
• Hazardous Substances Data: 93-02-7(Hazardous Substances Data)

Usage

Chemical Properties

yellow crystalline solid

Uses

2,5-Dimethoxybenzaldehyde is used in the preparation of 2,5-dimethoxyphenethylamine, which is utilized to prepare psychoactive drugs such as 2,5-dimethoxy-4-bromophenethylamine, 2,5-dimethoxy-4-iodophenethylamine and 4-Chloro-2,5-dimethoxy-phenethylamine. It acts as an intermediate in organic synthesis.

Application

2,5-Dimethoxybenzaldehyde, also known as 2C-H, is an organic compound and a benzaldehyde derivative. It can be used to produce 2,5-dimethoxyphenethylamine. 2C-H is also used to produce many other substituted phenethylamines such as 2C-B, 2C-I and 2C-C.

Preparation

2,5-Dimethoxybenzaldehyde synthesis: Anethole is oxidized to anisaldehyde , which after isolation is subjected to a BaeyerVilliger oxidation reaction with performic or peracetic acid. The O-formyl-4-methoxyphenol obtained this way is hydrolyzed . 4-Methoxyphenol is subsequently formylated using the Reimer-Tiemann method and the obtained 2-hydroxy-5-methoxybenzaldehyde is methylated with dimethylsulfate to 2,5-dimethoxybenzaldehyde.ReactionA : Anisaldehyde from anethole via oxidative cleavage: 20 g anise oil was suspended in a mixture of 150 mL water and 30 mL conc. sulfuric acid; addition of 55 g sodium bichromate at such a rate that the temperature did not exceed 40°C. The reaction mixture was extracted with 4 x 125 mL toluene and the solvent evaporated. The residual oil was vacuum distilled to yield 9.1 g anisaldehyde.B : O-formyl-4-methoxyphenol: 6 mL anisaldehyde was dissolved in 75 mL dichloromethane (DCM). A mixture of 12 g hydrogen peroxide and 10 mL conc. formic acid was added over 30 min. The reaction mixture was gently refluxed for 21 h.C: B 4-methoxyphenol: Evaporating the solvent from reaction mixture and taking up the residue in 100 mL aqueous NaOH (20%) (25 mL MeOH as co-solvent) yielded 4.1 g 4-methoxyphenol as a white crystalline product after the usual work-up and purification steps.D : Reimer-Tiemann formylation of 4-methoxyphenol: 124.1 g 4-methoxyphenol was dissolved in NaOH solution (320 g NaOH in 400 mL water). In total, 161 mL chloroform was added. The usual work-up and steam distillation yielded 109.8 g of a clear yellow oil that did not solidify upon standing at room temperature (GC/MS: 94% 2-hydroxy-5-methoxybenzaldehyde).E: D Methylation of 2-hydroxy-5-methoxybenzaldehyde: The yellow oil from was used without further purification. A 250 mL RB flask was charged with 100 mL acetone, 14 g anhydrous potassium carbonate and 10 g 2-hydroxy-5-methoxybenzaldehyde; the mixture was brought at reflux temperature and 11 g dimethyl sulfate was added. The reaction was continued for 4 hours. The solvent is evaporated and the crude end product crystallized in cold water. Recrystallization from EtOH/water yielded 8.3 g 2,5-dimethoxybenzaldehyde (GC/MS: 98%+ 2,5-dimethoxybenzaldehyde)

InChI:InChI=1/C9H10O3/c1-11-8-3-4-9(12-2)7(5-8)6-10/h3-6H,1-2H3

Synthetic route

2,5-dimethoxybenzyl alcohol (33524-31-1) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With potassium osmate(VI) dihydrate; potassium carbonate; potassium hexacyanoferrate(III) In water; acetonitrile at 60℃; for 0.75h; chemoselective reaction;	100%
With air; potassium carbonate In toluene at 20℃; for 8h;	99%
With aluminium trichloride; 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane dichromate for 0.0166667h; Oxidation;	96%

1,1-diacetoxy-1-(2,5-dimethoxyphenyl)methane (55669-73-3) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With [NO(1+)*18-crown-6*H(NO3)2(1-)]; silica gel In dichloromethane at 20℃; for 0.0833333h;	100%
With bismuth(III) chloride In chloroform for 0.166667h; deprotection; Heating;	99%
With aluminium trichloride In acetonitrile for 0.05h; Deacetylation; Heating;	99%

Dichloromethyl methyl ether (4885-02-3) + 1,4-dimethoxybezene (150-78-7) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With titanium tetrachloride In dichloromethane at 0℃;	100%
With titanium tetrachloride In dichloromethane at -5 - 20℃; for 1.5h; Reagent/catalyst; Temperature; Inert atmosphere;	97.6%
With titanium tetrachloride In dichloromethane at 20℃; for 0.25h;

octanol (111-87-5) + 2,5-dimethoxybenzyl alcohol (33524-31-1) → Octanal (124-13-0) + 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With air; potassium carbonate at 20℃; for 16h;	A 2% B 99%

1-Phenylethanol (98-85-1, 13323-81-4) + 2,5-dimethoxybenzyl alcohol (33524-31-1) → 2,5-dimethoxybenzaldehyde (93-02-7) + acetophenone (98-86-2)

Conditions	Yield
With air; potassium carbonate at 20℃; for 8h;	A 99% B 10%

2,5-dimethoxybenzaldehyde semicarbazone → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With aluminium trichloride; 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane dichromate at 20℃; for 0.0108333h;	96%

1,4-Dimethoxy-2-phenethyloxymethyl-benzene (121336-24-1) → 2-phenylethanol (60-12-8) + 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water at 20℃; for 2.5h;	A 95% B 16%

(2,5-dimethoxy-benzyloxy)-trimethyl-silane → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With aluminium trichloride; tetramethylammonium chlorochromate In acetonitrile for 1.08333h; Heating;	95%
With bismuth(III) chloride; benzyltriphenylphosphonium peroxymonosulfate In dichloromethane for 0.0583333h; microwave irradiation;	80%
With bismuth(III) chloride; benzyltriphenylphosphonium peroxymonosulfate In acetonitrile for 0.5h; Heating;	75%
With benzyltriphenylphosphonium chlorate; aluminium trichloride In acetonitrile for 8h; Heating;	75%
With aluminium trichloride; benzyltriphenylphosphonium chlorochromate In acetonitrile for 0.5h; Heating;	75%

2,5‐dimethoxybenzaldoxime (67184-41-2, 34967-19-6) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With 2-iodoxybenzoic acid; β‐cyclodextrin In water; acetone at 20℃; for 12h;	91%
With iodobenzene; β‐cyclodextrin; potassium bromide In water; acetone at 20℃; for 12h;	90%
With N-Bromosuccinimide; β‐cyclodextrin In water; acetone at 20℃; for 0.333333h;	80%

2-(2,5-dimethoxyphenyl)-1,3-dithiane (137709-38-7) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With 1,3,5-trichloro-2,4,6-triazine; dimethyl sulfoxide In dichloromethane at 20℃; for 1h;	90%

formaldehyd (50-00-0) + 1,4-dimethoxybezene (150-78-7) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With sulfuric acid; 2,3-dicyano-5,6-dichloro-p-benzoquinone In acetonitrile at 80℃; for 5h;	89%

(2,5-dimethoxyphenyl)acetic acid (1758-25-4) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With sodium azide; [bis(acetoxy)iodo]benzene In acetonitrile at 0 - 20℃; for 0.25h;	89%

dimethyl sulfate (77-78-1) + 2-hydroxy-5-methoxybenzaldehyde; potassium salt → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
In acetone at 35 - 40℃; for 2h; Product distribution / selectivity;	88.3%
With tetrabutylammomium bromide In isopropyl alcohol at 35 - 40℃; for 0.5h; Product distribution / selectivity;	70%
In n-heptane; N,N-dimethyl-formamide for 0.5h; Product distribution / selectivity; Heating / reflux;	62%

Sodio 5-methoxy-salicylaldehyde (79043-42-8) + dimethyl sulfate (77-78-1) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
In acetone for 3h; Product distribution / selectivity; Heating / reflux;	88.3%

2-(2,5-dimethoxy-benzyloxy)-tetrahydro-pyran → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With aluminum oxide; potassium permanganate for 0.25h; Product distribution; Further Variations:; Reagents; reaction times;	88%
With aluminium trichloride; tetramethylammonium chlorochromate In acetonitrile for 1h; Heating;	88%
With bismuth(III) chloride; benzyltriphenylphosphonium peroxymonosulfate In dichloromethane for 0.0666667h; microwave irradiation;	85%

2,5-Dihydroxybenzaldehyde (1194-98-5) + methyl iodide (74-88-4) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With potassium carbonate In acetone at 20℃; for 18h;	85%
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	73%
With potassium hydroxide
With potassium carbonate In acetone at 25℃; for 20h;
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 16h;	2.4 g

5-(2',5'-dimethoxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (117646-10-3) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With oxone In water; acetonitrile at 45℃; for 1h; Reagent/catalyst; Solvent; Temperature;	84%

2,5-dimethoxy-1-(2',2'-dicyanovinyl)benzene (2972-75-0) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With [bis(acetoxy)iodo]benzene In tetrahydrofuran at 20℃; for 1h;	78%

2-hydroxy-5-methoxybenzaldehyde (672-13-9) + dimethyl sulfate (77-78-1) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With potassium carbonate In acetone for 3h; Product distribution / selectivity; Heating / reflux;	77%
With sodium hydroxide
With sodium hydroxide In water at 65℃; for 0.5h; Yield given;

1-tert-butyldimethylsilyloxymethyl-2,5-dimethoxybenzene (161435-89-8) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With N-Bromosuccinimide; β‐cyclodextrin In ethyl acetate; acetone at 20℃; for 7h;	72%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 1,4-dimethoxybezene (150-78-7) → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With trichlorophosphate at 100℃; for 5h;	66%
With sodium hydroxide; pyrophosphoryl chloride 1) 100 deg C, 48 h; Yield given. Multistep reaction;

2-naphthyl pivalate (1503-86-2) + Cyclohexyl-[1-(2,5-dimethoxy-phenyl)-meth-(E)-ylidene]-amine → 2,5-dimethoxybenzaldehyde (93-02-7) + 5-methoxy-2-(naphthalen-2-yl)benzaldehyde (217074-77-6)

Conditions	Yield
Stage #1: 2-naphthyl pivalate; Cyclohexyl-[1-(2,5-dimethoxy-phenyl)-meth-(E)-ylidene]-amine With chromium dichloride; magnesium; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 40℃; for 48h; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 0.5h;	A 65% B 19%

2-naphthyl pivalate (1503-86-2) + C12H17NO2 → 2,5-dimethoxybenzaldehyde (93-02-7) + 5-methoxy-2-(naphthalen-2-yl)benzaldehyde (217074-77-6)

Conditions	Yield
Stage #1: 2-naphthyl pivalate; C12H17NO2 With chromium dichloride; magnesium; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 40℃; for 48h; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 0.5h;	A 28% B 61%

2-naphthyl pivalate (1503-86-2) + C28H25NO2 → 2,5-dimethoxybenzaldehyde (93-02-7) + 5-methoxy-2-(naphthalen-2-yl)benzaldehyde (217074-77-6)

Conditions	Yield
Stage #1: 2-naphthyl pivalate; C28H25NO2 With chromium dichloride; magnesium; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 40℃; for 48h; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 0.5h;	A 27% B 56%

Benzyl-[1-(2,5-dimethoxy-phenyl)-meth-(E)-ylidene]-amine → 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
Stage #1: Benzyl-[1-(2,5-dimethoxy-phenyl)-meth-(E)-ylidene]-amine With chromium dichloride; 2-naphthyl pivalate; magnesium; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 40℃; for 48h; Stage #2: With hydrogenchloride; water In tetrahydrofuran at 20℃; for 0.5h;	56%

1-(2,5-Dimethoxy-phenyl)-2-phenyl-ethanol (76246-95-2) → Benzyl acetate (140-11-4) + 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With lead(IV) acetate In benzene Heating;	A n/a B 55%

(+/-)-4-(2',5'-dimethoxyphenyl)-3-methylbutane-1,3-diol → 2,5-dimethoxybenzaldehyde (93-02-7) + (+/-)-4-(2',5'-dimethoxyphenyl)-3-hydroxy-3-methylbutanal (300661-24-9)

Conditions	Yield
With dipyridinium dichromate; 3 A molecular sieve; acetic acid In dichloromethane at 20℃; for 1.5h; Oxidation;	A 16% B 37%

1,4-dimethoxybezene (150-78-7) + formic acid ethyl ester (109-94-4) → ethyl 2,5-dimethoxy benzoate (81722-06-7) + 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
Stage #1: 1,4-dimethoxybezene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 2h; Stage #2: formic acid ethyl ester In tetrahydrofuran; hexane at -78℃; for 3h; Stage #3: With ethanol; iodine; potassium carbonate In tetrahydrofuran; hexane at -78 - 20℃; for 14h;	A 7% B 32%

(1S,4R)-1-Benzyl-4-[(S)-(2,5-dimethoxy-phenyl)-hydroxy-methyl]-2,5-dimethoxy-cyclohexa-2,5-dienecarbaldehyde → 2-benzyl-1,4-dimethoxybenzene (43037-60-1) + 2,5-dimethoxybenzaldehyde (93-02-7)

Conditions	Yield
With manganese(IV) oxide In dichloromethane at 21℃; for 5h; other reagent PDC;	A 23% B 30%

acetic anhydride (108-24-7) + 2,5-dimethoxybenzaldehyde (93-02-7) → 1,1-diacetoxy-1-(2,5-dimethoxyphenyl)methane (55669-73-3)

Conditions	Yield
With titanium tetrachloride at 20℃; for 15h; screw-capped vial; Inert atmosphere; neat (no solvent);	100%
With copper(II) sulfate	96%
With lithium trifluoromethanesulfonate at 20℃; for 36h;	90%

2,5-dimethoxybenzaldehyde (93-02-7) + acetone (67-64-1) → trans-1-(2,5-dimethoxyphenyl)-2-buten-3-one (118709-30-1)

Conditions	Yield
With sodium hydroxide at 23℃; for 6.5h;	100%
Stage #1: 2,5-dimethoxybenzaldehyde; acetone With L-proline In dimethyl sulfoxide at 20℃; for 48h; Stage #2: With hydrogenchloride In water; dimethyl sulfoxide for 3h;	62.5%
With sodium hydroxide at 20℃; for 0.5h;	53%

piperidine (110-89-4) + BARBITURIC ACID (67-52-7) + 2,5-dimethoxybenzaldehyde (93-02-7) → 5-(2,5-Dimethoxy-benzylidene)-pyrimidine-2,4,6-trione; compound with piperidine

Conditions	Yield
In methanol for 5h; Heating;	100%

ethylene glycol (107-21-1) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2-(2',5'-dimethoxyphenyl)-1,3-dioxolane (72054-76-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating;	100%
With toluene-4-sulfonic acid In benzene Heating;	97%
With toluene-4-sulfonic acid In benzene for 4h; Heating;	83%

2,5-dimethoxybenzaldehyde (93-02-7) + methylamine (74-89-5) → [1-(2,5-Dimethoxy-phenyl)-meth-(Z)-ylidene]-methyl-amine (114943-72-5)

Conditions	Yield
at 20℃; for 12h;	100%
In ethanol at 0 - 40℃;	90%
In methanol; water for 2h;

2,5-dimethoxybenzaldehyde (93-02-7) + 2,2-dimethoxyethylamine (22483-09-6) → acetaldehyde dimethyl acetal (54879-66-2)

Conditions	Yield
In toluene Heating;	100%
In toluene for 4h; Heating;	100%
With magnesium sulfate In chloroform at 20℃; for 24h;	100%
With magnesium sulfate In chloroform at 20℃; for 24h;	100%
In toluene for 4h; Reflux; Dean-Stark;

diethoxyphosphoryl-acetic acid ethyl ester (867-13-0) + 2,5-dimethoxybenzaldehyde (93-02-7) → (2E)-ethyl 3-(2,5-dimethoxyphenyl)propenoate (15804-86-1, 24393-64-4)

Conditions	Yield
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Stage #2: 2,5-dimethoxybenzaldehyde In tetrahydrofuran at 20℃; for 6h; Horner-Wadsworth-Emmons reaction;	100%
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran; mineral oil at 23℃; Inert atmosphere; Cooling with ice; Stage #2: 2,5-dimethoxybenzaldehyde In tetrahydrofuran; mineral oil at 0 - 23℃; for 0.5h; Inert atmosphere;	94%

thiosemicarbazide (79-19-6) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2,5-dimethoxybenzaldehyde thiosemicarbazone (329069-71-8)

Conditions	Yield
In neat (no solvent) for 0.25h; Milling; Green chemistry;	100%
With acetic acid In ethanol for 24h; Reflux;	82%
With sodium acetate In ethanol; water at 20℃; for 0.25h;
In ethanol Reflux;

2-acetyl benzo[b]thiophene (22720-75-8) + 2,5-dimethoxybenzaldehyde (93-02-7) → (E)-1-(1-benzothiophen-2-yl)-3-(2,5-dimethoxyphenyl)-2-propen-1-one

Conditions	Yield
With pyrrolidine; acetic acid In tetrahydrofuran for 13h; Aldol Condensation; Reflux; Inert atmosphere;	100%

1H-indene-1,3(2H)-dione (606-23-5) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2-(2,5-dimethoxybenzylidene)-1H-indene-1,3(2H)-dione (67200-96-8)

Conditions	Yield
With hydrogenchloride; acetic acid In ethanol; water at 50 - 60℃; Reagent/catalyst; Solvent;	99%
Stage #1: 1H-indene-1,3(2H)-dione With pyridine Stage #2: 2,5-dimethoxybenzaldehyde at 100℃; for 1h;	75%
With ethanol

malonic acid (141-82-2) + 2,5-dimethoxybenzaldehyde (93-02-7) → trans-2,5-dimethoxycinnamic acid (38489-74-6)

Conditions	Yield
Stage #1: 2,5-dimethoxybenzaldehyde With pyridine at 20℃; for 0.166667h; Inert atmosphere; Stage #2: malonic acid With piperidine for 5h; Reflux; Inert atmosphere;	99%
With piperidine; pyridine at 110℃;	88%
With piperazine for 0.075h; Knoevenagel condensation; microwave irradiation;	86%

2,5-dimethoxybenzaldehyde (93-02-7) + malononitrile (109-77-3) → 2,5-dimethoxy-1-(2',2'-dicyanovinyl)benzene (2972-75-0)

Conditions	Yield
With polystyrene-supported DABCO In methanol at 25℃; for 0.166667h; Knoevenagel Condensation; Green chemistry;	99%
With Zn(II), 1,3,5-benzene tricarboxylic acid and 4,4'-bipyridine based metal organic framework In methanol at 60℃; for 4h; Catalytic behavior; Temperature; Knoevenagel Condensation;	92%
With calcium ferrite In methanol for 0.666667h; Knoevenagel Condensation; Reflux; Green chemistry;	85%

2,5-dimethoxybenzaldehyde (93-02-7) → 2,5-dimethoxybenzyl alcohol (33524-31-1)

Conditions	Yield
With sodium tetrahydroborate In methanol at 0 - 20℃;	99%
With sodium tetrahydroborate In diethyl ether; water at 20℃; for 1h;	99%
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.333333h;	99%

trimethylsilyl cyanide (7677-24-9) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2-(2,5-dimethoxyphenyl)-2-trimethylsilyloxyacetonitrile (141367-35-3)

Conditions	Yield
With C29H38AlN4O2(1+)*CF3O3S(1-) at 20℃; for 0.333333h; Catalytic behavior; Inert atmosphere; Schlenk technique;	99%
With zinc(II) iodide for 1h; Ambient temperature;	90%
With [(3-isopropyl-1-(1R-phenylethyl)imidazol-2-ylidene)CpFe(CO)2]I In neat (no solvent) at 27℃; for 6h; Glovebox; Schlenk technique; UV-irradiation;	87%

2,5-dimethoxybenzaldehyde (93-02-7) → 2,5-dimethoxyphenol (18113-18-3)

Conditions	Yield
With bis(2-phenyltrifluoromethanesulfonate)diselenide; dihydrogen peroxide In dichloromethane at 20℃; for 3h;	99%
Stage #1: 2,5-dimethoxybenzaldehyde With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; Stage #2: With methanol; sodium hydroxide at 20℃; for 3h; Inert atmosphere;	98%
With Monoperoxyphthalic acid, magnesium salt In methanol at 20℃; for 18h; Reduction;	94%

2,5-dimethoxybenzaldehyde (93-02-7) → 2,5-dimethoxybenzonitrile (5312-97-0)

Conditions	Yield
With oxygen; copper; ammonium chloride In pyridine at 60℃; for 24h;	99%
Stage #1: 2,5-dimethoxybenzaldehyde With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane at 26℃; for 0.0833333h; Stage #2: With 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate In dichloromethane at 26℃; for 18h;	88%
With Nitroethane; ammonium acetate In acetic acid for 10h; Heating;

nitromethane (75-52-5) + 2,5-dimethoxybenzaldehyde (93-02-7) → 1-(2,5-dimethoxyphenyl)-2-nitroethanol (14438-63-2)

Conditions	Yield
With C12H24KO6*HO(1-) In methanol at 20℃; for 0.416667h; Henry reaction;	99%
With sodium hydroxide In ethanol; water at 10 - 15℃; for 0.5h; Temperature; Solvent; Reagent/catalyst;	96%
With {(C6H3C(CH3)3OCHNCH2CH2NCHO(CH3)3CC6H3)Co}; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 48h; Reagent/catalyst; Henry Nitro Aldol Condensation;	70%

1,2-bis(trimethylsiloxy)cyclobutene (17082-61-0) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2-((2,5-dimethoxyphenyl)(trimethylsilyloxy)methyl)-2-(trimethylsilyloxy)cyclobutanone

Conditions	Yield
With 2-Trifluoromethylbenzaldehyde; magnesium iodide In dichloromethane; benzene at 20℃; for 0.25h; Mukaiyama aldol coupling;	99%
With 4-O2NPhOMgI In dichloromethane at 20℃; Mukaiyama aldol reaction; Inert atmosphere;	93%

N-(4-aminophenyl)-N'-phenylurea (10141-46-5) + 2,5-dimethoxybenzaldehyde (93-02-7) → 1-[4-(2,5-dimethoxy-benzylamino)phenyl]-3-phenylurea (1173493-06-5)

Conditions	Yield
With sodium cyanoborohydride In methanol Reflux; Inert atmosphere;	99%

carbon tetrabromide (558-13-4) + 2,5-dimethoxybenzaldehyde (93-02-7) → 2-(2,2-dibromoethenyl)-1,4-dimethoxybenzene (1224168-51-7)

Conditions	Yield
Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at 0℃; for 0.666667h; Inert atmosphere; Stage #2: 2,5-dimethoxybenzaldehyde In dichloromethane at 0℃; Inert atmosphere;	99%
Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at 0℃; for 0.666667h; Inert atmosphere; Stage #2: 2,5-dimethoxybenzaldehyde In dichloromethane at 0℃; for 0.333333h; Inert atmosphere;	99%
With triphenylphosphine In dichloromethane at 0℃; for 1.25h; Inert atmosphere;

2,5-dimethoxybenzaldehyde (93-02-7) + 3-phenyliodonio-1,2,4-trioxo-1,2,3,4-tetrahydronaphthalenide (117560-06-2) → 2-(2,5-dimethoxyphenyl)-3-hydroxynaphthalene-1,4-dione (1240385-26-5)

Conditions	Yield
With boron trifluoride diethyl etherate In chloroform for 1h; Reflux;	99%

2,5-dimethoxybenzaldehyde (93-02-7) + methyl 2-naphthyl ketone (93-08-3) → (2E)-1-(2-naphthyl)-3-(2,5-dimethoxyphenyl)-2-propen-1-one (1332627-22-1)

Conditions	Yield
With potassium hydroxide In methanol; water at 20℃; for 24h; Aldol condensation;	99%
With sodium hydroxide In methanol; water at 20℃; for 15h; Claisen-Schmidt Condensation;	73%

Nitroethane (79-24-3) + 2,5-dimethoxybenzaldehyde (93-02-7) → (1S,2R)-1-(2,5-dimethoxyphenyl)-2-nitropropan-1-ol (1372810-65-5)

Conditions	Yield
With 1-ethyl-piperidine; 3,5-bistrifluoromethylbenzoic acid; bis((3,5-bis(trifluoromethyl)phenyl)ureido)-(salen)cobalt In tert-butyl methyl ether at -50℃; for 16h; Henry reaction; optical yield given as %ee; diastereoselective reaction;	99%

Nitroethane (79-24-3) + 2,5-dimethoxybenzaldehyde (93-02-7) → (1R,2S)-1-(2,5-dimethoxyphenyl)-2-nitropropan-1-ol (1372810-66-6)

Conditions	Yield
With 1-ethyl-piperidine; 3,5-bistrifluoromethylbenzoic acid; bis((3,5-bis(trifluoromethyl)phenyl)ureido)-(salen)cobalt In tert-butyl methyl ether at -50℃; for 16h; Henry reaction; optical yield given as %ee; diastereoselective reaction;	99%

nitromethane (75-52-5) + 2,5-dimethoxybenzaldehyde (93-02-7) → C10H13NO5

Conditions	Yield
With (2S,5R)-2-(methylaminomethyl)-1-methyl-5-phenylpyrrolidine; triethylamine; copper(ll) bromide In tetrahydrofuran at -25℃; for 39h; Henry Nitro Aldol Condensation; Inert atmosphere; Schlenk technique; enantioselective reaction;	99%

Upstream product

• 10538-51-9 2,5-dimethoxycinnamic acid 
• 546-67-8 lead(IV) tetraacetate 
• 64-19-7 acetic acid 
• 150-78-7 1,4-dimethoxybezene 
• 4755-77-5 Ethyl oxalyl chloride 
• 74-90-8 hydrogen cyanide 
• 672-13-9 2-hydroxy-5-methoxybenzaldehyde 
• 74-88-4 methyl iodide 
• 1194-98-5 2,5-Dihydroxybenzaldehyde 
• 33524-31-1 2,5-dimethoxybenzyl alcohol 
• 68-12-2 N,N-dimethyl-formamide 
• 93-61-8 N-methyl-N-phenylformamide 
• 7647-01-0 hydrogenchloride 
• 7446-70-0 aluminium trichloride 

Downstream Products

• 115604-02-9 3,3'?((2,5?dimethoxy)methylene)?bis?(4?hydroxy?2H?chromene?2?one) 
• 80777-95-3 2-benzoyl-3-(2,5-dimethoxy-phenyl)-acrylonitrile 
• 19785-02-5 (E)-1,4-dimethoxy-2-(prop-1-enyl)benzene 
• 26122-90-7 2-amino-3-(2,5-dihydroxyphenyl)propanoic acid 
• 18790-57-3 (E)-1,4-dimethoxy-2-(2-nitroprop-1-en-1-yl) benzene 
• 134040-27-0 2,5-dimethoxy-β-methyl-β-nitrostyrene 
• 67200-96-8 2-(2,5-dimethoxybenzylidene)-1H-indene-1,3(2H)-dione 
• 40276-11-7 (E)-1,4-dimethoxy-2-(2-nitrovinyl) benzene 
• 108536-18-1 β-dimethoxy-2,5 phenyl nitro ethylene 
• 38489-74-6 trans-2,5-dimethoxycinnamic acid 
• 682805-45-4 (2,5-dimethoxy-benzylidene)-malonic acid 
• 5529-38-4 2,5-dimethoxy-4'-nitro-stilbene 
• 33769-67-4 (Z)-3-(2,5-dimethoxyphenyl)-2-phenylprop-2-enoic acid 
• 110662-23-2 N,N'-bis-(2,5-dimethoxy-benzyliden)-ethylenediamine 

Relevant articles and documents

Decomposition of methoxamine in aqueous solution: identification of the decomposition products.

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Preparation method of 2,5-dimethoxyphenylacetic acid

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of 2,5-dimethoxyphenylacetic acid, wherein the method comprises the following steps: A,reacting 1,4-dimethoxybenzene in a formylation system to obtain 2,5-dimethoxybenzaldehyde; B, reacting the 2,5-dimethoxybenzaldehyde obtained in the step A with a reducing agent, extracting a reaction system, then combining organic phases, drying, concentrating under reduced pressure and distilling a crude product to obtain 2,5-dimethoxybenzyl alcohol; C, reacting the 2,5-dimethoxybenzyl alcoholobtained in the step B with a bromination reagent to obtain 2-bromomethyl-1,4-dimethoxybenzene; and D, reacting the 2-bromomethyl-1,4-dimethoxybenzene obtained in the step C with magnesium or butyl lithium and carbon dioxide in a solvent to obtain the 2,5-dimethoxyphenylacetic acid. The yield and the total yield of the 2,5-dimethoxyphenylacetic acid obtained by the method disclosed by the invention are both higher than those of 2,5-dimethoxyphenylacetic acid synthesized by a Willegerdt-Kindler method.

Oxidation of Benzylic Alcohols to Aromatic Aldehydes by DMSO/Water/I2: A Chemoselective Oxidation

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SUBSTITUTED CHROMEN-4-ONE FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION

The present invention provides novel compounds having the general formula: (I) wherein R1 to R10, Gi, G2 and m are as described herein, compositions including the impounds and methods of using the compounds for the treatment of hepatitis B.