6231-18-1

Basic information

• Product Name: 2,6-Dimethoxypyridine
• Synonyms: 2,6-DIMETHOXYPYRIDINE;2,6-Dimethoxypyridine, 98+%;2,6-Dimethoxypyridine,99%;2,6- twoMethoxypyridine;Pyridine, 2,6-dimethoxy-
• CAS NO: 6231-18-1
• Molecular Formula: C₇H₉NO₂
• Molecular Weight: 139.15
• EINECS: 228-334-4
• Product Categories: compounds of pyridine;Pyridines derivates;C7 and C8;Heterocyclic Building Blocks;Pyridines;Building Blocks;C7 to C8;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 6231-18-1.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 178-180 °C(lit.)
• Flash Point: 143 °F
• Appearance: clear colorless to light yellow liquid
• Density: 1.053 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.32mmHg at 25°C
• Refractive Index: n20/D 1.503(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 1.57±0.10(Predicted)
• BRN: 1525332
• CAS DataBase Reference: 2,6-Dimethoxypyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-Dimethoxypyridine(6231-18-1)
• EPA Substance Registry System: 2,6-Dimethoxypyridine(6231-18-1)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-37/38-41-36/37/38-20/21/22
• Safety Statements: 26-39-36/37/39-36
• RIDADR: 1993
• WGK Germany: 3
• HazardClass: 3.2
• PackingGroup: III
• Hazardous Substances Data: 6231-18-1(Hazardous Substances Data)

Usage

Chemical Properties

clear colorless to light yellow liquid

InChI:InChI=1/C7H9NO2/c1-9-6-4-3-5-7(8-6)10-2/h3-5H,1-2H3

Synthetic route

2,6-Dibromopyridine (626-05-1) + methanol (67-56-1) → 2,6-dimethoxypyridine (6231-18-1)

Conditions	Yield
With sodium hydroxide	94%
With 5-(di(adamantan-1-yl)phosphino)-1′,3′,5′-triphenyl-1′H-1,4′-bipyrazole; palladium diacetate; caesium carbonate In toluene at 80℃; for 24h;	77%
With 5-(di-tert-butylphosphino)-1′, 3′, 5′-triphenyl-1′H-[1,4′]bipyrazole; tris-(dibenzylideneacetone)dipalladium(0); potassium hydroxide at 0.1℃; for 3h; Inert atmosphere;

2,6-dichloropyridine (2402-78-0) + methanol (67-56-1) → 2,6-dimethoxypyridine (6231-18-1)

Conditions	Yield
With sodium hydroxide for 8h; Reflux;	94%

2,6-Dibromopyridine (626-05-1) + sodium methylate (124-41-4) → 2,6-dimethoxypyridine (6231-18-1)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃;	65%

2,6-Dibromopyridine (626-05-1) → 2,6-dimethoxypyridine (6231-18-1)

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide at 80℃; for 2h;	65%

2,6-dichloropyridine (2402-78-0) + sodium methylate (124-41-4) → 6-chloro-2-methoxypyridine (17228-64-7) + 2,6-dimethoxypyridine (6231-18-1)

Conditions	Yield
In methanol for 25h; Heating;	A 80 % Spectr. B 20 % Spectr.

2,6-dimethoxypyridine (6231-18-1) + methyl iodide (74-88-4) → N-methyl-6-methoxy-2-(1H)-pyridone (6231-16-9)

Conditions	Yield
at 40℃; under 4500450 Torr; for 24h; Hilbert-Johnson reaction;	100%
at 80℃; for 24h;	72%

2,6-dimethoxypyridine (6231-18-1) → 3-iodo-2,6-dimethoxypyridine (214360-56-2)

Conditions	Yield
Stage #1: 2,6-dimethoxypyridine With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; zinc dichloro(N,N,N′,N′-tetramethylethylenediamine) In tetrahydrofuran; hexane at 20℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran; hexane at 20℃; Concentration; Time; Inert atmosphere; regioselective reaction;	98%
With iodine; silver(I) acetate In acetonitrile at 23℃; for 0.5h;	80%
With iodine; sodium hydrogencarbonate at 20℃;	41%
With dichloro(N,N,N’,N‘-tetramethylethylenediamine)zinc; 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran at 20℃; for 2h;

2,6-dimethoxypyridine (6231-18-1) → 3-bromo-2,6-dimethoxypyridine (13445-16-4)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 80℃; for 18h;	97%
With N-Bromosuccinimide In acetonitrile for 10h; Reflux;	89%
With N-Bromosuccinimide In acetonitrile for 10h; Heating;	85%

2,6-dimethoxypyridine (6231-18-1) + 1-Iodo-perfluorodecane (423-62-1) → C17H8F21NO2

Conditions	Yield
With (dppf)Ni(o-tol)Cl; caesium carbonate In neat (no solvent) at 130℃; for 16h; Inert atmosphere; Sealed tube;	96%

2,6-dimethoxypyridine (6231-18-1) + bis(pinacol)diborane (73183-34-3) → C13H20BNO4

Conditions	Yield
With C25H36O2P2Ru In tetrahydrofuran at 120℃; for 12h; Inert atmosphere; Sealed tube;	96%

2,6-dimethoxypyridine (6231-18-1) + zinc dibromide → [Zn(2,6-dimethoxypyridine)4][Zn2Br6] (497233-01-9)

Conditions	Yield
In dichloromethane under Ar atm. to suspn. ZnBr2 in CH2Cl2 2 equiv. 2,6-dimethoxypyridine was added and stirred at room temp. for 12 h; solvent was removed under vac. at 40°C; elem. anal.;	95%
In diethyl ether under Ar atm. to soln. ZnBr2 in ether 2,6-dimethoxypyridine was added; ppt. was washed with ether; elem. anal.;

2,6-dimethoxypyridine (6231-18-1) + para-methylphenylmagnesium bromide (4294-57-9) → 2,6-di-p-tolylpyridine (14435-88-2)

Conditions	Yield
With C68H72Cl2N6NiP2 In tetrahydrofuran at 25℃; for 24h; Inert atmosphere;	95%

2,6-dimethoxypyridine (6231-18-1) + phosphorous acid trimethyl ester (121-45-9) → dimethyl (2,6-dimethoxypyridin-3-yl)phosphonate

Conditions	Yield
With ammonium peroxydisulfate; tris(2,2′-bipyrazine-N1,N1′)ruthenium(II) hexafluorophosphate In acetonitrile at 25℃; for 20h; Inert atmosphere; Irradiation;	93%

2,6-dimethoxypyridine (6231-18-1) + o-chlorobenzoyl chloride (609-65-4) → 2-chlorophenyl(2,6-dimethoxypyridin-3-yl)ketone (1335212-81-1)

Conditions	Yield
Stage #1: 2,6-dimethoxypyridine With n-butyllithium; N,N,N,N,-tetramethylethylenediamine; 2,2,6,6-tetramethylpiperidinyl-lithium; copper(l) chloride In tetrahydrofuran; hexanes at 20℃; for 2h; Inert atmosphere; Stage #2: o-chlorobenzoyl chloride In tetrahydrofuran; hexanes at 0 - 20℃; for 16h; Inert atmosphere;	91%
Stage #1: 2,6-dimethoxypyridine With N,N,N,N,-tetramethylethylenediamine; 2,2,6,6-tetramethylpiperidinyl-lithium; copper(l) chloride In tetrahydrofuran at 20℃; for 2h; Schlenk technique; Inert atmosphere; Stage #2: o-chlorobenzoyl chloride In tetrahydrofuran at 20℃; Schlenk technique; Inert atmosphere;	91%

2,6-dimethoxypyridine (6231-18-1) + benzyl bromide (100-39-0) → C14H16NO2(1+)*Br(1-)

Conditions	Yield
In acetonitrile Reflux;	90%

2,6-dimethoxypyridine (6231-18-1) + aniline (62-53-3) → 6‐methoxy‐N‐phenylpyridin‐2‐amine (1282585-58-3)

Conditions	Yield
With potassium hexamethylsilazane In tetrahydrofuran at 100℃; for 16h; Inert atmosphere; Schlenk technique; Sealed tube; Green chemistry;	86%

2,6-dimethoxypyridine (6231-18-1) + triethyl phosphite (122-52-1) → diethyl (2,6-dimethoxypyridin-3-yl)phosphonate

Conditions	Yield
With ammonium peroxydisulfate; tris(2,2′-bipyrazine-N1,N1′)ruthenium(II) hexafluorophosphate In acetonitrile at 25℃; for 20h; Inert atmosphere; Irradiation;	84%

2,6-dimethoxypyridine (6231-18-1) + ethyl iodide (75-03-6) → C8H11NO2

Conditions	Yield
at 100℃; under 6000600 Torr; for 48h; Hilbert-Johnson reaction;	83%

2,6-dimethoxypyridine (6231-18-1) + N-((4-chlorobenzyl)oxy)-N-methylacetamide (1352918-92-3) → 3-(4-chlorobenzyl)-2,6-dimethoxypyridine (1352918-69-4)

Conditions	Yield
With boron trifluoride diethyl etherate In dichloromethane at 45℃; for 24h; Friedel Crafts alkylation; Inert atmosphere;	83%

2,6-dimethoxypyridine (6231-18-1) → 3-chloro-2,6-dimethoxypyridine

Conditions	Yield
With N-chloro-succinimide; dimethyl sulfoxide In chloroform at 25℃; for 2h; Reagent/catalyst; Schlenk technique;	83%
Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide / acetonitrile / 10 h / Reflux 2.1: n-butyllithium; isopropylmagnesium chloride / tetrahydrofuran; hexane / 0.75 h / -2 - 0 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere View Scheme

2,6-dimethoxypyridine (6231-18-1) + diethyl (bromodifluoromethyl)phosphonate (65094-22-6) → diethyl ((2,6-dimethoxypyridin-3-yl)difluoromethyl)phosphonate

Conditions	Yield
With potassium phosphate; fac-tris(2-phenylpyridinato-N,C2')iridium(III) In dichloromethane at 20℃; for 36h; Inert atmosphere; Irradiation;	83%

1,1-Diphenylethylene (530-48-3) + 2,6-dimethoxypyridine (6231-18-1) → C21H19NO2

Conditions	Yield
With CoIII(dimethylglyoximate)2(4-NMe2-C5H4N)Cl; 3,6‐di‐tert‐butyl‐9‐mesityl‐10‐phenylacridin‐10‐ium tetrafluoroborate In 1,2-dichloro-ethane at 20℃; for 24h; Heck Reaction; Irradiation; Inert atmosphere; regioselective reaction;	83%

2,6-dimethoxypyridine (6231-18-1) → 2,6-dimethoxypyridine-3-boronic acid (221006-70-8)

Conditions	Yield
Stage #1: 2,6-dimethoxypyridine With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 3h; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78℃; for 1h; Stage #3: With hydrogen bromide In water pH=6;	82%
With n-butyllithium; Triisopropyl borate; diisopropylamine In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	80%

2,6-dimethoxypyridine (6231-18-1) + triisopropyl phosphite (116-17-6) → diisopropyl (2,6-dimethoxypyridin-3-yl)phosphonate

Conditions	Yield
With ammonium peroxydisulfate; tris(2,2′-bipyrazine-N1,N1′)ruthenium(II) hexafluorophosphate In acetonitrile at 25℃; for 20h; Inert atmosphere; Irradiation;	82%

2,6-dimethoxypyridine (6231-18-1) + N-(4-acetylphenyl)-1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]methanesulfonamide → 2,6-dimethoxy-3-(trifluoromethyl)pyridine (1365122-59-3)

Conditions	Yield
In acetonitrile Solvent; Irradiation;	82%

2,6-dimethoxypyridine (6231-18-1) → 2,6-dimethoxy-3,5-dibromopyridine (16727-44-9)

Conditions	Yield
With bromine In chloroform at 20℃; for 4h;	80%

2,6-dimethoxypyridine (6231-18-1) + Triisopropyl borate (5419-55-6) → 2,6-dimethoxy-3-pyridinyl-boronic acid (1219744-53-2)

Conditions	Yield
Stage #1: 2,6-dimethoxypyridine With n-butyllithium; diisopropylamine In tetrahydrofuran at -78℃; for 3h; Inert atmosphere; Stage #2: Triisopropyl borate In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	80%

2,6-dimethoxypyridine (6231-18-1) + [tungsten(trispyrazoylborate)(NO)(trimethylphosphine)(η2-benzene)] → [TpW(NO)(PMe3)(3,4-η2-2,6-dimethoxypyridine)]

Conditions	Yield
In hexane stirring a suspn. of tungsten complex and ligand in hexanes for 26 h; obtained as a mixt. of diastereomers;	79%
In pentane to a soln. of complex and pyridine-compound was added pentane, the mixt.was stirred for 26 h; the mixt. was added to pentane, ppt. was dried in vac.;	79%

N-(trifluoromethyl)acyloxyphthalimide (5672-90-2) + 2,6-dimethoxypyridine (6231-18-1) → 2,6-dimethoxy-3-(N-phthalimido)pyridine (848827-76-9)

Conditions	Yield
With tris[2-phenylpyridinato-C2,N]iridium(III) In acetonitrile at 20℃; for 24h; Sealed tube; Irradiation;	79%

pyrrolidine (123-75-1) + 2,6-dimethoxypyridine (6231-18-1) → 2-(piperidin-1-yl)-6-(pyrrolidin-1-yl)pyridine

Conditions	Yield
With sodium hydride; lithium iodide In tetrahydrofuran at 0 - 60℃; for 5h; Inert atmosphere; Sealed tube;	79%

2,6-dimethoxypyridine (6231-18-1) + ((trispyrazol-1-yl)hydroborane)Mo(NO)(4-(dimethylamino)pyridine)(3,4-η2-α,α,α-trifluorotoluene) → Mo(tris(pyrazolyl)borate)(NO)(4-(dimethylamino)pyridine)(3,4-η2-2,6-dimethoxypyridine)

Conditions	Yield
In tetrahydrofuran for 3.5h; Glovebox; Inert atmosphere;	78.6%

2,6-dimethoxypyridine (6231-18-1) + dibutylamine (111-92-2) → N,N-dibutyl-6-methoxypyridin-2-amine

Conditions	Yield
Stage #1: dibutylamine With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 0.166667h; Inert atmosphere; Schlenk technique; Stage #2: 2,6-dimethoxypyridine In tetrahydrofuran; hexane at 60℃; for 0.166667h; Inert atmosphere; Schlenk technique;	78%

2,6-dimethoxypyridine (6231-18-1) → 3-bromo-2,6-dimethoxypyridine (13445-16-4) + 2,6-dimethoxy-3,5-dibromopyridine (16727-44-9)

Conditions	Yield
With bromine In tetrachloromethane at -40 - -30℃;	A 76% B n/a
With pyridinium hydrobromide perbromide In tetrachloromethane Rt, overnight, then reflux, 2 h;	A 30% B 15%
With potassium bromide In water; dimethyl sulfoxide at 25℃; Irradiation; Overall yield = 69 percent;

Upstream product

• 141-86-6 2.6-diaminopyridine 
• 149-73-5 trimethyl orthoformate 
• 2402-78-0 2,6-dichloropyridine 
• 67-56-1 methanol 
• 124-41-4 sodium methylate 
• 626-05-1 2,6-Dibromopyridine 

Downstream Products

• 13445-16-4 3-bromo-2,6-dimethoxypyridine 
• 16727-44-9 3,5-dibromo-2,6-dimethoxypyridine 
• 626-06-2 2,6-dihydroxypyridine 
• 14435-88-2 2,6-di-p-tolylpyridine 
• 1039775-46-6 2,6-dimethoxy-3-(4-methoxyphenyl)pyridine 
• 1335212-81-1 2-chlorophenyl(2,6-dimethoxypyridin-3-yl)ketone 
• 1335212-80-0 2,6-dimethoxypyridin-3-yl(4-(trifluoromethyl)phenyl)ketone 
• 121643-45-6 2,6-dimethoxypyridine-3-carbonitrile 
• 221006-70-8 2,6-dimethoxypyridine-3-boronic acid 
• 885963-28-0 3-hydroxy-2,6-dimethoxypyridine 
• 220998-37-8 (+/-)-2,2',6,6'-tetramethoxy-bis(diphenylphosphinoyl)-3,3'-bipyridine 
• 220998-36-7 3-bromo-2,6-dimethoxy-4-diphenylphosphinoylpyridine 
• 220998-35-6 3-bromo-2,6-dimethoxy-4-diphenylphosphino-pyridine 
• 934286-83-6 C₂₂H₃₁NO₄Si 

Relevant articles and documents

Preparation method of ortho-alkoxy substituted pyridine compound

The invention provides a preparation method of an ortho-alkoxy substituted pyridine compound, the preparation method comprises the following step: reacting an ortho-amino substituted pyridine compound with an ortho-formate compound in the presence of a nitrite compound to generate the ortho-alkoxy substituted pyridine compound. The method has the advantages of high efficiency, low cost, environmental protection and the like.

A convenient and practical synthesis of anisoles and deuterated anisoles by palladium-catalyzed coupling reactions of aryl bromides and chlorides

Synthesis of anisole: Aryl and heteroaryl halides undergo selective C-O cross-coupling reactions with methanol in the presence of a Pd(OAc) 2/L3 catalyst system. The corresponding ethers were obtained under mild conditions in good yields. The catalytic methodology was also used for the synthesis of labeled deuterated anisoles in good yields (see scheme). Copyright

Further studies of regioselective alkoxydehalogenation of 2,4-dichloroquinolines, 2,6-dichloropyridine and 2,4-dichloronitrobenzene

Regioselective alkoxydehalogenation reactions using solid alkoxide in toluene have been studied. 2-Alkoxy-4-haloquinolines were obtained from 2,4-dichloroquinolines. With 2,6-dichloropyridine, α-regioselectivity occurred to furnish the 2-alkoxy-6-chloropyridine. The reaction failed with 2,4-dichloronitrobenzene indicating that alkoxide surface contact with a basic heterocyclic nitrogen lone pair was essential for success. Comparative studies with the standard alkoxydehalogenation reaction (alcoholic alkoxide solution) have been performed, all compounds have been identified by 1H and 13C NMR.