3900-45-6

Usage

Uses

Used in Pharmaceutical Industry:
2-Acetyl-6-methoxynaphthalene is used as an impurity reference substance for the identification and quantification of related compounds in the manufacturing and quality control processes of naproxen, a widely used NSAID. Its role is crucial in ensuring the safety, efficacy, and quality of naproxen products.
As Naproxen Impurity L:
2-Acetyl-6-methoxynaphthalene is used as an impurity reference for the United States Pharmacopeia (USP) related compound L. It aids in the standardization and quality assessment of naproxen products, ensuring that they meet the required specifications and guidelines.

Flammability and Explosibility

Nonflammable

InChI:InChI=1/C13H12O2/c1-9(14)10-3-4-12-8-13(15-2)6-5-11(12)7-10/h3-8H,1-2H3

Synthetic route

2-ethynyl-6-methoxynaphthalene (129113-00-4) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With water In neat (no solvent) at 100℃; for 4h; Green chemistry;	98%
With water; silver trifluoromethanesulfonate for 5.5h; Heating;	94%
With silver(I) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate; water In ethyl acetate at 80℃; for 12h; Green chemistry; chemoselective reaction;	92%

1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium tert-butylate; copper(I) triflate; 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole In N,N-dimethyl-formamide at 25℃; for 0.5h; Catalytic behavior;	97%
With 1-hydroxy-1H-1,2,3-benziodoxathiole 1,3,3-trioxide; Oxone; cetyltrimethylammonim bromide In water at 20℃; for 2h; Green chemistry; chemoselective reaction;	93%
With chromium (VI) oxide In acetonitrile at 135℃; Fixed-bed flow reactor; Inductive heating; High pressure;	92%

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid (22204-53-1) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With iron(III) chloride; oxygen In N,N-dimethyl-formamide at 110℃;	91%
With (2,2'-dipyridyl)bis(5-methyl-2-(4-fluoro)phenylpyridine-N,C)iridium(III) hexafluorophosphate; oxygen; sodium carbonate; 1,1'-diethyl-4,4'-bipyridinium diperchlorate In dimethyl sulfoxide at 20℃; under 760.051 Torr; for 16h; Irradiation;	80%
With mercury(II) fluoride; oxygen In acetonitrile at 25℃; for 24h; Irradiation;	78%
With potassium permanganate In dichloromethane for 24h;	26%

1,2,4,5-tetramethylbenzene (95-93-2) + 5-bromo-6-methoxy-2-acetylnaphthalene (84167-74-8) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
aluminium trichloride	90.6%
aluminium trichloride	90.6%

5-bromo-6-methoxy-2-acetylnaphthalene (84167-74-8) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With hydrogenchloride; sodium hydroxide; aluminium trichloride In water; toluene	88.7%
aluminium trichloride	88.2%
aluminium trichloride	88.2%

2-Methoxynaphthalene (93-04-9) + acetyl chloride (75-36-5) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With aluminium trichloride In dichloromethane at 25℃; for 12h;	88%
With hydrogenchloride; aluminium trichloride In chloroform; nitrobenzene	63%
With aluminium trichloride In nitrobenzene for 24h;	49%

1-acetyl-2-methoxynaphthalene (5672-94-6) → 2-Methoxynaphthalene (93-04-9) + 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With scandium tris(trifluoromethanesulfonate) In nitromethane at 50℃; for 18h; Product distribution;	A 86% B 9%

2-­(6-­methoxynaphthalen-­2-­yl)acetaldehyde (54828-56-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With acetic anhydride	86%
With acetic anhydride	86%

2-Methoxynaphthalene (93-04-9) + acetic anhydride (108-24-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1-acetyl-2-methoxynaphthalene (5672-94-6)

Conditions	Yield
With antimony(III) trifluoromethanesulfonate; lithium perchlorate In nitromethane at 50℃; for 5h; Acetylation; Friedel-Crafts acylation;	A 75% B n/a
With H-beta In 1,2-dichloro-ethane at 120℃; for 3h; Kinetics; Reagent/catalyst; Friedel-Crafts Acylation; Sealed tube;	A 18.3% B 18.4%
With scandium tris(trifluoromethanesulfonate) In nitromethane at 50℃; for 18h; Friedel-Crafts reaction;	A 15% B 85 % Chromat.

2-methoxy-6-(prop-1-en-2-yl)-naphthalene (34352-92-6) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; oxygen; 2,5-Dimercapto-1,3,4-thiadiazole In acetonitrile at 20 - 80℃; under 760.051 Torr; for 15h; Schlenk technique;	75%
Multi-step reaction with 3 steps 1: 1) 10 M BH3*SMe2, 2) 10percent aq. NaOH, 30percent aq. H2O2 / 1) THF, 0 deg C, 1 h, 2) rt, 6 h 2: 94 percent / oxalyl chloride, DMSO, NEt3 / CH2Cl2 / -78 °C 3: 35 percent / KMnO4, MgSO4 / acetone / 2 h View Scheme

naproxen (23981-80-8) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; N,N,N',N'-tetramethylguanidine In acetonitrile at 20℃; for 6h; Irradiation;	72%
With sodium anthraquinone-2-sulfonate In water; acetonitrile at 20℃; for 18h; Irradiation; Green chemistry;	95 %Chromat.

methanol (67-56-1) + carbon monoxide (201230-82-2) + 2-(1-Iodo-vinyl)-6-methoxy-naphthalene (129113-01-5) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + methyl 2-(6-methoxynaphthalen-2-yl)acrylate (129113-02-6)

Conditions	Yield
With triethylamine; palladium In tetrahydrofuran at 65℃; under 15200 Torr; for 17h;	A 9% B 70%

2-Bromo-6-methoxynaphthalene (5111-65-9) + N-Methoxy-N-methylacetamide (78191-00-1) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With n-butyllithium In tetrahydrofuran; hexane at -78 - -70℃; for 1.5h;	68%

1-(6-methoxy-2-naphthyl)-prop-1-ene (90708-65-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
Stage #1: 1-(6-methoxy-2-naphthyl)-prop-1-ene With N-iodo-succinimide; cetyltrimethylammonim bromide In 1,4-dioxane; water at 115℃; for 0.25h; Microwave irradiation; Stage #2: With dipyridinium dichromate; acetic acid In 1,4-dioxane; water at 115℃; for 0.25h; Microwave irradiation;	67%

2-Methoxynaphthalene (93-04-9) + acetic anhydride (108-24-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1-(6-methoxynaphthalen-1-yl)ethanone (58149-89-6)

Conditions	Yield
With phosphotungstic acid In tetrachloromethane at 140℃; for 3h; Solvent; Reflux; regioselective reaction;	A 22% B 56%
With phosphotungstic acid In nitrobenzene at 140℃; for 3h; Reflux; regioselective reaction;	A 38% B 8%

2-Methoxynaphthalene (93-04-9) + acetic anhydride (108-24-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With Amberlyst 16 WET at 90℃; for 66h;	53.8%
With zeolitic material In chlorobenzene at 100℃; for 24h; Reagent/catalyst;

1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) + sodium cyanide (143-33-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (22204-53-1) + (R)-2-(6-methoxy-2-naphthyl)propionic acid (23979-41-1)

Conditions	Yield
Multistep reaction. Title compound not separated from byproducts;	A 51% B n/a C n/a

1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) + sodium cyanide (143-33-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + (S)-(-)-2-(6-methoxy-2-naphthalene)propionitrile (133097-35-5) + (R)-(+)-2-(6-methoxy-2-naphthalene)propionitrile (108865-01-6)

Conditions	Yield
Stage #1: 1-(6-methoxy-2-naphthyl)ethanol With oxygen; (-)-sparteine; palladium diacetate In toluene at 80℃; under 760 Torr; Stage #2: With pyridine; phosphorus tribromide In diethyl ether at -20 - 0℃; Stage #3: sodium cyanide In N,N-dimethyl-formamide at 80℃; Title compound not separated from byproducts;	A 51% B n/a C n/a

1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + (S)-1-[2-(6-methoxynaphthyl)]ethanol (77301-42-9, 108781-65-3, 125712-80-3, 119341-64-9) + (R)-1-(6-methoxynaphthalen-2-yl)ethanol (77301-42-9, 119341-64-9, 125712-80-3, 108781-65-3)

Conditions	Yield
With oxygen; (-)-sparteine; palladium diacetate In toluene at 80℃; under 760 Torr;	A 51% B n/a C n/a
With ammonium sulfate cross-linked glutaraldehyde compound-modified protein complex In water; dimethyl sulfoxide; isopropyl alcohol at 40℃; for 48h; Solvent;	A n/a B n/a C n/a

1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + (S)-1-(6-methoxy-2-naphthyl)-1-bromoethane + (R)-(+)-1-(6-methoxy-2-naphthyl)-1-bromoethane

Conditions	Yield
Stage #1: 1-(6-methoxy-2-naphthyl)ethanol With oxygen; (-)-sparteine; palladium diacetate In toluene at 80℃; under 760 Torr; Stage #2: With pyridine; phosphorus tribromide In diethyl ether at -20 - 0℃; Title compound not separated from byproducts;	A 51% B n/a C n/a

2-Methoxynaphthalene (93-04-9) + acetyl chloride (75-36-5) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1-acetyl-2-methoxynaphthalene (5672-94-6)

Conditions	Yield
Stage #1: acetyl chloride With aluminum (III) chloride In 1,2-dichloro-ethane at 0℃; for 0.75h; Friedel-Crafts Acylation; Inert atmosphere; Stage #2: 2-Methoxynaphthalene In 1,2-dichloro-ethane at 0℃; for 4h; Friedel-Crafts Acylation; Inert atmosphere;	A 51% B 46%

2-(6-methoxy-2-naphthyl)propanal (27602-75-1) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + naproxen (23981-80-8)

Conditions	Yield
With potassium permanganate; magnesium sulfate In acetone for 2h;	A 35% B 50%

6-methoxy-2-naphthoyl chloride (58601-32-4) + methylzinc iodide (18815-73-1) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
With toluene

2-Methoxynaphthalene (93-04-9) + acetyl chloride (75-36-5) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1,6-diacetyl-2-methoxy-naphthalene (5672-98-0)

Conditions	Yield
With aluminium trichloride; nitrobenzene

2-Methoxynaphthalene (93-04-9) + acetyl chloride (75-36-5) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1,3-bis-(6-methoxy-[2]naphthyl)-but-2-en-1-one (102876-54-0)

Conditions	Yield
With aluminium trichloride; nitrobenzene

1-acetyl-2-methoxynaphthalene (5672-94-6) → 2-Methoxynaphthalene (93-04-9) + 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1-(7-methoxy-1-naphthalenyl)ethanone (3453-55-2)

Conditions	Yield
With indium(III) chloride In nitrobenzene at 50℃; for 3h;	A 52 % Chromat. B 32 % Chromat. C 6 % Chromat.
With indium(III) chloride In nitrobenzene at 50℃; for 12h;	A 38 % Chromat. B 23 % Chromat. C 8 % Chromat.

naproxen (23981-80-8) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + methyl 2-(6-methoxy-2-naphthyl)propionate (30012-51-2) + 1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9) + 2-methoxy-6-(1-methoxyethyl)naphthalene (132367-16-9) + 1,1'-bis(6-methoxy-2-naphtyl)ethoxyethane

Conditions	Yield
With ammonium cerium(IV) nitrate In methanol for 0.5h; Product distribution; var. molar ratio of the oxidant; other oxidant; also anodic oxidation; sodium salt of naproxen;

4,4-Dimethoxy-3-[1-(4-methoxy-phenyl)-meth-(E)-ylidene]-pentan-2-one (123207-06-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6)

Conditions	Yield
at 475 - 500℃; vapor-phase pyrolysis; Yield given;
at 470 - 510℃; drip type pyrrolysis unit filled with fine Vycor chips was used; Yield given;

2-Methoxynaphthalene (93-04-9) + acetic anhydride (108-24-7) → 6-methoxy-2-acetylnaphthalene (3900-45-6) + 1-acetyl-2-methoxynaphthalene (5672-94-6) + 1-(7-methoxy-1-naphthalenyl)ethanone (3453-55-2)

Conditions	Yield
With indium(III) chloride In 1,2-dichloro-ethane at 50℃; for 3h; Yield given. Yields of byproduct given;
With HBEA-15 In nitrobenzene for 50h; Product distribution; Kinetics; Further Variations:; Reagents; Solvents; Temperatures; reaction time;	A 68.4 % Chromat. B 23.4 % Chromat. C 8.2 % Chromat.
With H-BEA-15 zeolite In nitrobenzene at 99.85℃; under 750.06 Torr; for 1h; Product distribution; Further Variations:; reaction time;
Stage #1: acetic anhydride With Zr4+-zeolite beta(ie) In neat (no solvent) for 0.0333333h; Inert atmosphere; Stage #2: 2-Methoxynaphthalene In neat (no solvent) at 140℃; for 36h; Inert atmosphere;

6-methoxy-2-acetylnaphthalene (3900-45-6) → 1-(6-methoxy-2-naphthyl)ethanol (108781-65-3, 119341-64-9, 125712-80-3, 77301-42-9)

Conditions	Yield
With hydrogen; palladium on activated charcoal; 5% Pd on active carbon In tetrahydrofuran	100%
With methanol; sodium tetrahydroborate at 20℃; for 3h;	99%
Stage #1: 6-methoxy-2-acetylnaphthalene With bis-{[N,N′-bis(2,6-(di-isopropyl)phenyl)imidazol-2-ylidene]-(1H-1,2,4-triazol-1-yl)}copper(I) In tetrahydrofuran at 55℃; for 6h; Stage #2: With sodium hydroxide In methanol; water at 25℃; for 1.5h;	98%

chloro-trimethyl-silane (75-77-4) + 6-methoxy-2-acetylnaphthalene (3900-45-6) + potassium cyanide (151-50-8) → 2-(6-methoxy-2-naphthyl)-2-(trimethylsilyloxy)propiononitrile (107727-73-1)

Conditions	Yield
In N,N-dimethyl-formamide at 60℃; for 13.5h;	100%

6-methoxy-2-acetylnaphthalene (3900-45-6) + trimethyl sulfonium hydrogen sulfate → 2-(6-methoxynaphth-2-yl)-1,2-propylene oxide (27602-74-0)

Conditions	Yield
With sodium hydroxide In dichloromethane at 30℃; for 3h;	99.4%

6-methoxy-2-acetylnaphthalene (3900-45-6) → (R)-1-(6-methoxynaphthalen-2-yl)ethanol (77301-42-9, 119341-64-9, 125712-80-3, 108781-65-3)

Conditions	Yield
Stage #1: 6-methoxy-2-acetylnaphthalene With cobalt(II) acetate; bis-[2-((4S)-4-phenyl-4,5-dihydro-oxazol-2-yl)-phenyl]-amine In tetrahydrofuran at 65℃; Inert atmosphere; Stage #2: With diethoxymethylane In tetrahydrofuran at 65℃; optical yield given as %ee; enantioselective reaction;	99%
Stage #1: 6-methoxy-2-acetylnaphthalene With (R)-(3,4,5-trimethoxyphenyl)-MeOBIPHEP; TPGS-750-M; copper(II) acetate monohydrate In water; toluene at 22℃; for 1.5h; Sealed tube; Inert atmosphere; Schlenk technique; Green chemistry; Stage #2: In water; toluene at 0 - 22℃; Catalytic behavior; Temperature; Reagent/catalyst; Sealed tube; Inert atmosphere; Schlenk technique; Green chemistry; enantioselective reaction;	91%
With borane-THF; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; enantioselective reaction;	89%

6-methoxy-2-acetylnaphthalene (3900-45-6) + ketene t-butyldimethylsilyl methyl acetal (77086-38-5) → C22H32O4Si

Conditions	Yield
With C90H89F6N3O8P2S2 In diethyl ether at 20℃; for 12h; Temperature; Mukaiyama Aldol Addition; enantioselective reaction;	99%

morpholine (110-91-8) + 6-methoxy-2-acetylnaphthalene (3900-45-6) → 2-(6-methoxynaphthalen-2-yl)-1-morpholinoethanethione (53077-21-7)

Conditions	Yield
With toluene-4-sulfonic acid; sulfur at 130℃; for 45h; Willgerodt-Kindler reaction;	98%
With sulfur at 140℃;

6-methoxy-2-acetylnaphthalene (3900-45-6) → 2-iodo-1-(6-methoxy-2-naphthyl)ethanone (1000375-33-6)

Conditions	Yield
With iodine; copper(II) oxide In methanol for 2h; Heating;	98%
Stage #1: 6-methoxy-2-acetylnaphthalene With iodine In methanol Stage #2: With sodium sulfite

6-methoxy-2-acetylnaphthalene (3900-45-6) → 5-bromo-6-methoxy-2-acetylnaphthalene (84167-74-8)

Conditions	Yield
With Oxone; ammonium bromide In methanol at 20℃; for 0.666667h; regioselective reaction;	97%
With dihydrogen peroxide; ammonium bromide; acetic acid at 20℃; for 5h;	81%
With N-Bromosuccinimide In acetonitrile at 0 - 20℃; for 4h; Inert atmosphere;	80%
With phenyltrimethylammonium tribromide In tetrahydrofuran; water at 25℃; for 25h;	90 % Chromat.

6-methoxy-2-acetylnaphthalene (3900-45-6) → 1-(6-hydroxy-2-naphthyl)ethan-1-one (10441-41-5)

Conditions	Yield
With hydrogenchloride In dichloromethane; water at 85℃; for 4h;	96%
With hydrogenchloride In water for 2h; Reflux;	95.7%
With hydrogenchloride In water at 90℃; for 2h;	91%

diethoxyphosphoryl-acetic acid ethyl ester (867-13-0) + 6-methoxy-2-acetylnaphthalene (3900-45-6) + sodium methylate (124-41-4) → methyl (E)-3-(6-methoxynaphthalen-2-yl)but-2-enoate (901766-67-4)

Conditions	Yield
In methanol; N,N-dimethyl-formamide at 0 - 25℃; for 20h; Horner-Wadsworth-Emmons reaction;	96%

6-methoxy-2-acetylnaphthalene (3900-45-6) → 2-bromo-1-(6-methoxy-2-naphthyl)ethanone (10262-65-4)

Conditions	Yield
With copper(I) bromide In ethanol at 60℃; Inert atmosphere;	95%
With 1-butyl-3-methylimidazolium tribromide In neat (no solvent) for 0.166667h;	93.6%
With potassium bromate; water; potassium bromide In ethanol for 0.75h;	77%

6-methoxy-2-acetylnaphthalene (3900-45-6) + benzaldehyde (100-52-7) → (E)-1-(6-methoxynaphthalen-2-yl)-3-phenylprop-2-en-1-one

Conditions	Yield
With fly-ash:H2SO4 Aldol condensation; Microwave irradiation; Neat (no solvent);	95%
With SiO2-H3PO4 Aldol Condensation; Microwave irradiation;	85%

6-methoxy-2-acetylnaphthalene (3900-45-6) → 6-methoxy-2-naphthylamine (13101-88-7)

Conditions	Yield
With methanol; O-benzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid at 23℃; for 9h; Reagent/catalyst; Inert atmosphere;	95%
With O-benzenesulfonyl-acetohydroxamic acid ethyl ester; toluene-4-sulfonic acid In methanol at 20℃; for 24h; Inert atmosphere;	90%
Multi-step reaction with 2 steps 1: HN3, H2SO4 / CHCl3 2: aq. H2SO4 / ethanol View Scheme
With sulfuric acid; trifluoroacetic acid In ethanol; water

4-Methylbenzyl alcohol (589-18-4) + 6-methoxy-2-acetylnaphthalene (3900-45-6) → 1-(6-methoxy naphthalen-2-yl)-3-p-tolylpropan-1-ol

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane; rhodium(III) acetylacetonate; potassium hydroxide In toluene at 110℃; for 4h; Sealed tube;	95%

6-methoxy-2-acetylnaphthalene (3900-45-6) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → (E)-3-(dimethylamino)-1-(6-methoxynaphthalen-2-yl)prop-2-en-1-one

Conditions	Yield
at 120℃; for 48h; Inert atmosphere;	95%

diethyl cyanophosphonate (2942-58-7) + 6-methoxy-2-acetylnaphthalene (3900-45-6) + lithium cyanide (2408-36-8) → 3-cyano-1,5-diphenylpentan-3-yl diethylphosphate

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.5h;	95%

6-methoxy-2-acetylnaphthalene (3900-45-6) + indole-2,3-dione (91-56-5) → 2-(6-methoxynaphthalen-2-yl)quinoline-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In water Pfitzinger Quinoline Synthesis; Reflux;	94%
With potassium hydroxide

6-methoxy-2-acetylnaphthalene (3900-45-6) + 5-Bromo-1H-indole-2,3-dione (87-48-9) → 6-bromo-2-(6-methoxynaphthalen-2-yl)quinoline-4-carboxylic acid

Conditions	Yield
With potassium hydroxide In water Reflux;	94%
With potassium hydroxide

6-methoxy-2-acetylnaphthalene (3900-45-6) → <1-(6-Methoxy-2-naphthyl)ethyl>amin (133097-30-0)

Conditions	Yield
With 4-methoxy-N-(1-(naphthalen-2-yl)ethylidene)aniline; ammonium formate In methanol at 80℃; for 12h; Inert atmosphere; chemoselective reaction;	94%
With ammonium acetate; ammonia; hydrogen; nickel In 1,4-dioxane at 100℃; under 76000.1 Torr; for 3h;	82%
With ammonium acetate; sodium cyanoborohydride
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride / methanol / 4 h / 50 °C / Inert atmosphere 2: raney nickel / methanol / 16 h / 80 °C / Inert atmosphere View Scheme

6-methoxy-2-acetylnaphthalene (3900-45-6) → 1-(6-methoxynaphthalen-2-yl)ethanone oxime (3893-38-7)

Conditions	Yield
With hydroxylamine hydrochloride In methanol at 50℃; for 4h; Inert atmosphere;	93%

6-methoxy-2-acetylnaphthalene (3900-45-6) + 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane (5123-13-7) → 1-(6-methoxynaphthalen-2-yl)-1-phenylethanol (1188303-98-1)

Conditions	Yield
Stage #1: 6-methoxy-2-acetylnaphthalene; 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane With bis(1,5-cyclooctadiene)nickel (0); N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene hydrochloride; cesium fluoride In toluene at 30 - 80℃; Inert atmosphere; Stage #2: With 2,2'-iminobis[ethanol] In tetrahydrofuran; toluene at 20℃; Inert atmosphere;	93%

6-methoxy-2-acetylnaphthalene (3900-45-6) → C13H14N2O

Conditions	Yield
With hydrazine hydrate In ethanol at 20℃; for 12h;	93%

trimethyl phosphonoacetate (5927-18-4) + 6-methoxy-2-acetylnaphthalene (3900-45-6) → 3-(6-methoxynaphthalen-2-yl)but-2-enoic acid methyl ester (136691-28-6)

Conditions	Yield
Stage #1: trimethyl phosphonoacetate; 6-methoxy-2-acetylnaphthalene With lithium hexamethyldisilazane at 10 - 20℃; for 0.0833333h; Stage #2: 6-methoxy-2-acetylnaphthalene In tetrahydrofuran at 50℃; for 14h;	92%

6-methoxy-2-acetylnaphthalene (3900-45-6) → 2-methoxy-6-ethylnaphthalene (21388-17-0)

Conditions	Yield
With palladium 10% on activated carbon In methanol; chlorobenzene at 25℃; for 2h; Sealed tube;	91%
With sodium tetrahydroborate; trifluoroacetic acid at 0 - 20℃;	60%
With hydrazine hydrate; diethylene glycol at 120℃; Versetzen mit KOH und Kochen des Reaktionsgemisches unter Abdestillieren des entstehenden Wassers;

methyl magnesium iodide (917-64-6) + 6-methoxy-2-acetylnaphthalene (3900-45-6) → 2-methoxy-6-(1-hydroxy-1-methylethyl)naphthalene (34352-83-5)

Conditions	Yield
In diethyl ether 1.) 20 deg C, 10 h, 2.) reflux, 30 min;	90%

6-methoxy-2-acetylnaphthalene (3900-45-6) → (S)-1-[2-(6-methoxynaphthyl)]ethanol (77301-42-9, 108781-65-3, 125712-80-3, 119341-64-9)

Conditions	Yield
Stage #1: 6-methoxy-2-acetylnaphthalene With C32H41CrN3O2Si; C7H14O4Si In toluene at -40 - 20℃; for 2h; Stage #2: With potassium carbonate In methanol for 1h; enantioselective reaction;	90%
With Daucus carota root In water at 20℃; for 42h;	78%
Daucas carota root; extract of In water at 37 - 40℃; for 42h; pH=7.0; Conversion of starting material; Enzymatic reaction; Aqueous phosphate buffer;	78%

Upstream product

• 58601-32-4 6-methoxy-2-naphthoyl chloride 
• 18815-73-1 methylzinc iodide 
• 93-04-9 2-Methoxynaphthalene 
• 75-36-5 acetyl chloride 
• 67-56-1 methanol 
• 201230-82-2 carbon monoxide 
• 129113-01-5 2-(1-Iodo-vinyl)-6-methoxy-naphthalene 
• 27602-75-1 2-(6-methoxy-2-naphthyl)propanal 
• 5672-94-6 1-acetyl-2-methoxynaphthalene 
• 5111-65-9 2-Bromo-6-methoxynaphthalene 
• 78191-00-1 N-Methoxy-N-methylacetamide 
• 37414-52-1 2-(6-methoxy-2-naphthyl)-propyl alcohol 
• 54828-56-7 2--(6--methoxynaphthalen--2--yl)acetaldehyde 
• 95-93-2 1,2,4,5-tetramethylbenzene 

Downstream Products

• 101736-65-6 3t-[2]furyl-1-(6-methoxy-[2]naphthyl)-propenone 
• 88407-85-6 3-(6-methoxy-naphthalen-2-yl)-3-methyl-oxiranecarboxylic acid ethyl ester 
• 23981-48-8 methyl 6-methoxy-2-naphthylacetate 
• 10262-65-4 2-bromo-1-(6-methoxy-2-naphthyl)ethanone 
• 52997-56-5 α,α'-dibromoacetyl-2 methoxy-6 naphtalene 
• 2471-70-7 2-methoxy-6-naphthoic acid 
• 32405-50-8 1,1-bis(pyridinium)methane diiodide 
• 23981-47-7 6-methoxy-2-naphthylacetic acid 
• 84167-74-8 5-bromo-6-methoxy-2-acetylnaphthalene 
• 133097-30-0 <1-(6-Methoxy-2-naphthyl)ethyl>amin 
• 104765-81-3 (E)-1-(6-methoxynaphthalen-2-yl)-3-phenylprop-2-en-1-one 
• 881846-71-5 [1-(6-Methoxy-naphthalen-2-yl)-eth-(E)-ylidene]-phenyl-amine 
• 68520-00-3 1-(6-(dimethylamino)naphthalen-2-yl)ethan-1-one 
• 1999-64-0 6-ethyl-2-naphthol 

Relevant academic research and scientific papers

Remarkable effect of lithium salts in Friedel-Crafts acylation of 2-methoxynaphthalene catalyzed by metal triflates

In the presence of a catalytic amount of a metal triflate such as Sb(OTf)3 or Ga(OTf)3, 2-methoxynaphthalene reacted with acetic anhydride in nitromethane-lithium perchlorate to afford 2-acetyl-6-methoxynaphthalene, a well-known intermediate for the synthesis of naproxen, in a high yield. (C) 2000 Elsevier Science Ltd.

Enhancement in activity and shape selectivity of zeolite BEA by phosphate treatment for 2-methoxynaphthalene acylation

Pore-engineering of large pores of zeolite BEA by phosphate treatment effectively narrowed the pores with the creation of new acid sites. Phosphate modification of BEA with lower loading was more effective in pore modification without affecting the zeolite structure. Pyrophosphates and polyphosphates are mainly responsible for the narrowing of the zeolite pores. Both the activity and shape selectivity for 2-acetyl-6-methoxynaphthalene were enhanced in the acylation of 2-methoxynaphthalene. At higher concentration of phosphates, conversion and selectivity decreased due to dealumination. 1% P loading was found to be optimum for the acylation of 2-methoxynaphthalene. With the optimized phosphate modification of BEA, high selectivity of 78% to 2-acetyl-6-methoxynaphthalene was achieved with 77% conversion.

Synthesis of bridged biarylbisquinones and effects of biaryl dihedral angles on photo- and electro-chemical properties

A series of bridged biarylbisquinones, QBINOLs 1-4, and their corresponding monomers, QNaphs 5-6, were designed to demonstrate the influence of biaryl conformation on the photo- and electro-chemical properties of the molecules. All target compounds were synthesized from the Diels-Alder reaction between silyl enol ethers of the corresponding naphthyl or binaphthyl derivatives and p-benzoquinone. Addition of an OMe auxochrome or formation of the dimeric structures affect the absorption spectra and the energy band gap (Eg), but not the reduction potentials of the molecules. Narrowing the dihedral angles of the QBINOLs by shortening methylene bridges limited the contribution of bridging OR auxochromes and therefore resulted in lower HOMO levels and larger Eg.

Al-ITQ-7, a Shape-Selective Zeolite for Acylation of 2-Methoxynaphthalene

Acylation of 2-methoxynaphthalene with acetic anhydride has been carried out with a tridirectional 12-member ring pore zeolite named ITQ-7, which has a slightly smaller pore diameter than zeolite Beta. ITQ-7 is as active as Beta but gives better selectivity to 2-acetyl-6-methoxynaphthalene (2-AMN). This is due to the differences in the relative diffusion coefficients of 2-AMN and 1-acetyl-2-methoxynaphthalene (1-AMN), whose ratios are 2.7 and 15.5 in Beta and ITQ-7, respectively. In general, it can be said that when decreasing the zeolite crystallite size, the reaction rate increases, although the selectivity to 2-AMN decreases.

Fluorogenic kinetic assay for high-throughput discovery of stereoselective ketoreductases relevant to pharmaceutical synthesis

Enantiomerically pure 1-(6-methoxynaphth-2-yl) and 1-(6-(dimethylamino)naphth-2-yl) carbinols are fluorogenic substrates for aldo/keto reductase (KRED) enzymes, which allow the highly sensitive and reliable determination of activity and kinetic constants of known and unknown enzymes, as well as an immediate enantioselectivity typing. Because of its simplicity in microtiter plate format, the assay qualifies for the discovery of novel KREDs of yet unknown specificity among this vast enzyme superfamily. The suitability of this approach for enzyme typing is illustrated by an exemplary screening of a large collection of short-chain dehydrogenase/reductase (SDR) enzymes arrayed from a metagenomic approach. We believe that this assay format should match well the pharmaceutical industry's demand for acetophenone-type substrates and the continuing interest in new enzymes with broad substrate promiscuity for the synthesis of chiral, non-racemic carbinols.

Acylation of 2-methoxynaphthalene in the presence of modified zeolite HBEA

The influence of postsynthesis treatment such as calcination and acid treatment of zeolite HBEA has been studied in the acylation of 2-methoxynaphthalene with acetic anhydride. The contribution of the inner and outer surface of zeolite HBEA is examined by conversion and product selectivity to a bulky product, which can be formed only on the outer surface of HBEA, and to a linear product, which can be formed on the inner and outer surfaces. Calcination under high heating rate enhances the catalytic activity of the inner surface due to the formation of extraframework alumina species in the micropores. FTIR-adsorption experiments of the bulky probe molecule 2,4,6-tri-tert-butylpyridine, which does not fit into the micropores, revealed that these alumina species are located preferentially in the micropores of HBEA. Acid treatment increases the catalytic activity of the outer surface due to the extraction of catalytically active extraframework alumina species out of the micropores and due to the formation of silanol groups, respectively.

Acylation of 2-methoxynaphthalene and isobutylbenzene over zeolite beta

The acylation of 2-methoxynaphthalene (2MN) and isobutylbenzene using several zeolite beta samples having varius Si/Al ratios and crystal sizes to examine whether external surface sites could be eliminated to enhance the catalyst performance to obtain a viable acylation catalyst for the formation of precursors to the nonsteroidal anti-inflammatory agents naproxen and ibuprofen. Zeolite beta was active for the acylation of 2MN but was not selective to the desired product, 2-acetyl-6-methoxynaphthalene (2,6-AMN). Mild operating conditions (temperature and acylating agent concentration) could be used to obtain reasonable conversions and to limit catalyst deactivation. The other key product, 1-acetyl-2-methoxynaphthalene (1,2-AMN) formed on the external surface of the zeolite, while 2,6-AMN occurred in the zeolite pores. Thus, the selectivity to 2,6-AMN was enhanced on zeolite beta samples having a larger crystal size, on which most of the acid sites could be passivated by coating the crystals with a layer of amorphous silica. The amount of surface coating on the large crystals determined the yield of and the selectivity to 2,6-AMN. Isobutylbenzene was less reactive than 2MN but the desired product, 4-isobutylacetophenone, was always obtained since the isobutyl group provides for the para position being the preferred sites for acylation. For isobutylbenzene, the zeolite external surface contributed significanlty to the formation of 4-isobutylacetophenone. Zeolite beta with a small crystal size was, thus, the most favored catalyst for this reaction.

Development of a High-Throughput Screen for Protein Catalysts: Application to the Directed Evolution of Antibody Aldolases

A semiautomated high-throughput system has been developed to express and purify proteins and assay their catalytic activity. The screen can be used to evolve activity, selectivity, and expression levels of proteins directly or in combination with selections. To illustrate its potential, the system was applied to the directed evolution of catalytic antibodies with aldolase activity.

Oxidation of 2-methoxy-6-(1-methylethyl)naphthalene with oxygen

Aerobic oxidation of 2-methoxy-6-(1-methyl-ethyl)naphthalene to hydroperoxide, alcohol, and ketone, is reported. These compounds, particularly 2-acetyl-6-meth-oxynaphthalene, are important intermediates in naproxen synthesis. N-Hydroxyphthalimide is shown here to be an efficient catalyst for oxidation to the hydroperoxide, 2-methoxy-6-(1-hydroperoxy-1-methylethyl) naphthalene, with a yield of 87%. However, the ketone and alcohol were obtained with lower yields, with a maximum yield of 13% for the ketone and 27% for the alcohol, using N-hydroxyphthal-imide and Cu(II) acetylacetonate as a catalyst. The synthesis of the products 2-acetyl-6-methoxynaphthalene and 2-methoxy-6-(1-hydroxy-1-methylethyl)naphthalene via an initial oxidation step to the hydroperoxide followed by a hydroperoxide decomposition step is shown to be more efficient; the ketone and alcohol were obtained from 2-methoxy-6-(1-methylethyl)naphthalene with yields of 40 and 56%, respectively.

Regioselective acylation of 2-methoxy naphthalene catalyzed by supported 12-Phosphotungstic acid

12-Phosphotungstic acid supported on silica gel, zirconium sulfate, and a combination of silica gel and zirconium sulfate (50% w/w) were employed as solid acid catalysts for regioselective acylation of 2-methoxynaphtalene with acetic anhydride. 1-(6-Methoxynaphthalen-2-yl)ethanone (2,6-AMN), a commercially important intermediate for production of Naproxen, was obtained with excellent selectivity (>98%) at 67-68% conversion using 12-phosphotungstic acid supported on silica gel 20% (w/w) in refluxing tetrachloroethane. The unreacted starting material can be easily separated from the product by a simple crystallization from nonane.