59576-26-0

Basic information

• Product Name: 2-Acetyl-4-methylpyridine
• Synonyms: 2-ACETYL-4-METHYLPYRIDINE;1-(4-METHYL-PYRIDIN-2-YL)-ETHANONE;2-ACETYL-4-METHYLPYRIDIN;4-methyl-2-acetylpyridine;2-Acetyl-4-picoline;2-Acetyl-4-Methylpiridine
• CAS NO: 59576-26-0
• Molecular Formula: C₈H₉NO
• Molecular Weight: 135.16
• Product Categories: Pyridine;Heterocyclic Compounds;Pyridines;C7 and C8;Heterocyclic Building Blocks;Building Blocks;C8 to C9;Chemical Synthesis;Heterocyclic Building Blocks
• Mol File: 59576-26-0.mol
• Article Data: 9

Chemical Properties

• Melting Point: 30-34 °C(lit.)
• Boiling Point: 227.1 °C at 760 mmHg
• Flash Point: 203 °F
• Appearance: /
• Density: 1.036 g/cm³
• Vapor Pressure: 0.0788mmHg at 25°C
• Refractive Index: 1.512
• Storage Temp.: 0-10°C
• Solubility: soluble in Methanol
• PKA: 3.82±0.10(Predicted)
• CAS DataBase Reference: 2-Acetyl-4-methylpyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Acetyl-4-methylpyridine(59576-26-0)
• EPA Substance Registry System: 2-Acetyl-4-methylpyridine(59576-26-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 59576-26-0(Hazardous Substances Data)

Usage

Chemical Properties

Crystals

Uses

2-Acetyl-4-methylpyridine may be used in the synthesis of:3,5-bis(4,4"-dimethyl-2,2′:6′,2′′-terpyridin-4′-yl)-1-bromobenzene1,3-bis(4,4"-dimethyl-2,2′:6′,2′′-terpyridin-4′-yl)-5-methylbenzene2-(3′,3′-bis(ethylthio)-1′-oxoprop-2′-en-1′-yl)-4-methylpyridine2-(3′-(N,N-dimethylamino)-1′-oxoprop-2′-en-1′-yl)-4-methylpyridine

General Description

2-Acetyl-4-methylpyridine is a substituted pyridine that can be prepared from 2-bromo-4-methylpyridine.

InChI:InChI=1/C8H9NO/c1-6-3-4-9-8(5-6)7(2)10/h3-5H,1-2H3

Synthetic route

2-Bromo-4-picoline (4926-28-7) + N,N-dimethyl acetamide (127-19-5) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
Stage #1: 2-Bromo-4-picoline With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 - 0.5h; Stage #2: N,N-dimethyl acetamide In diethyl ether; hexane at 20℃; for 2 - 14.5h; Product distribution / selectivity;	59%
Stage #1: 2-Bromo-4-picoline With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667h; Stage #2: N,N-dimethyl acetamide In diethyl ether; hexane at 20℃; for 14.5h;	59%
With n-butyllithium In diethyl ether; hexane	37%

2-Cyano-4-methylpyridin (1620-76-4) + methyl magnesium iodide (917-64-6) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
Stage #1: 2-Cyano-4-methylpyridin; methyl magnesium iodide In diethyl ether; benzene at 0 - 20℃; for 2h; Inert atmosphere; Stage #2: With water; ammonium chloride In diethyl ether; benzene Inert atmosphere;	52%
With diethyl ether; benzene Behandeln des Reaktionsgemisches mit wss.Ammoniumchlorid-Loesung;

picoline (108-89-4) + paracetaldehyde (123-63-7) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
With tert.-butylhydroperoxide; iron(II) sulfate; trifluoroacetic acid In acetonitrile for 4h; Heating;	20%

2-Bromo-4-picoline (4926-28-7) → 2-acetyl-4-methylpyridine (59576-26-0)

4-Methyl-2-isovalerylpyridine → 2-acetyl-4-methylpyridine (59576-26-0) + 2,2-Dimethyl-1-(4-methyl-pyridin-2-yl)-cyclopropanol + cis-3-Methyl-1-<2-(4-methylpyridyl)>-1-cyclobutanol + trans-3-Methyl-1-<2-(4-methylpyridyl)>-1-cyclobutanol

Conditions	Yield
In tert-butyl alcohol; benzene for 5h; Irradiation;
In tert-butyl alcohol; benzene for 5h; Quantum yield; Irradiation;

picoline (108-89-4) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 30 percent / silver nitrate, ammonium persulfate, conc. H2SO4 / H2O; CH2Cl2 / 3 h / 40 °C 2: benzene; 2-methyl-propan-2-ol / 5 h / Irradiation View Scheme

2-Amino-4-methylpyridine (695-34-1) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: diazonium reaction View Scheme

2-Cyano-4-methylpyridin (1620-76-4) + methylmagnesium bromide (75-16-1) → 2-acetyl-4-methylpyridine (59576-26-0)

Conditions	Yield
Stage #1: 2-Cyano-4-methylpyridin; methylmagnesium bromide In tetrahydrofuran; diethyl ether at -20 - -10℃; Stage #2: With hydrogenchloride; water In tetrahydrofuran; diethyl ether at -40℃; for 0.0833333h;

2-acetyl-4-methylpyridine (59576-26-0) + 2-aminobenzenesulfonic acid sodium salt (13846-13-4) → C14H13N2O3S(1-)*Na(1+)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene; ethanol Reflux;	97%

furfural (98-01-1) + 2-acetyl-4-methylpyridine (59576-26-0) → C13H11NO2

Conditions	Yield
With sodium hydroxide In methanol; water at 20℃; for 2h;	97%

2-acetyl-4-methylpyridine (59576-26-0) → C8H11NO

Conditions	Yield
Stage #1: 2-acetyl-4-methylpyridine With trimethylaluminum; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane; 3,3'-bis-(3,5-bis-trifluoromethyl-phenyl)-[1,1']binaphthalenyl-2,2'-diol In toluene at 20℃; for 2h; Glovebox; Inert atmosphere; Stage #2: With methanol for 0.5h; enantioselective reaction;	97%

2-acetyl-4-methylpyridine (59576-26-0) + 2-methoxy-1-naphthaldehyde (5392-12-1) → (E)-3-(2-methoxynaphthalen-1-yl)-1-(4-methylpyridin-2-yl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 1h; Inert atmosphere;	96%

2-acetyl-4-methylpyridine (59576-26-0) + oxalic acid diethyl ester (95-92-1) → ethyl 4-(4-methylpyridin-2-yl)-2,4-dioxobutanoate (741288-24-4)

Conditions	Yield
With sodium ethanolate In ethanol at 20℃;	95%
Stage #1: oxalic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 0.166667h; Stage #2: 2-acetyl-4-methylpyridine In ethanol for 0.5h; Stage #3: With hydrogenchloride; water Product distribution / selectivity; more than 3 stages;	82%
Stage #1: 2-acetyl-4-methylpyridine; oxalic acid diethyl ester With sodium ethanolate In ethanol at 20 - 60℃; for 9h; Stage #2: With water In diethyl ether; ethanol Product distribution / selectivity;

2-acetyl-4-methylpyridine (59576-26-0) → 1-(4-methyl-1-oxido-2-pyridinyl)ethanone (1563017-51-5)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0℃;	88%

2-acetyl-4-methylpyridine (59576-26-0) + 6-bromo-2-methoxynaphthalene-1-carbaldehyde (247174-18-1) → (E)-3-(6-bromo-2-methoxynaphthalen-1-yl)-1-(4-methylpyridin-2-yl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In methanol at 5 - 10℃; Inert atmosphere;	83%

2-acetyl-4-methylpyridine (59576-26-0) + trans-2-phenylethene-1-sulfonyl fluoride (405-18-5) → 6-(4-methylpyridin-2-yl)-4-phenyl-3,4-dihydro-1,2-oxathiine 2,2-dioxide

Conditions	Yield
With nickel(II) nitrate hexahydrate; potassium carbonate In acetonitrile at 20℃; for 24h;	82%

2-acetyl-4-methylpyridine (59576-26-0) + carbon disulfide (75-15-0) + ethyl iodide (75-03-6) → 2-(3',3'-bis(ethylthio)-1'-oxoprop-2'-en-1'-yl)-4-methylpyridine (170653-78-8)

Conditions	Yield
With potassium tert-butylate In tetrahydrofuran Ambient temperature;	81%

2-acetyl-4-methylpyridine (59576-26-0) → 2-bromo-1-(4-methylpyridin-2-yl)ethanone hydrobromide

Conditions	Yield
With hydrogen bromide; bromine; acetic acid at 20℃; for 2h; Inert atmosphere;	81%
With bromine In HBr-AcOH; diethyl ether; acetic acid	10.8 g (63 %)

2-acetyl-4-methylpyridine (59576-26-0) + 3,4-dimethylbenzaldehyde (5973-71-7) → 1-[2-(4-methyl)pyridyl]-3-(3,4-dimethylphenyl)propen-1-one

Conditions	Yield
Stage #1: 3,4-dimethylbenzaldehyde With sodium hydroxide In ethanol; water at 20℃; Stage #2: 2-acetyl-4-methylpyridine In ethanol; water at 20℃; for 0.166667h;	81%

2-acetyl-4-methylpyridine (59576-26-0) + 3,3-bis(methylsulfanyl)-1-pyridin-2-ylprop-2-en-1-one (78570-34-0) → 4-methyl-4'-(methylthio)-2,2':6',2"-terpyridine (108295-36-9)

Conditions	Yield
Stage #1: 2-acetyl-4-methylpyridine With potassium tert-butylate In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 3,3-bis(methylsulfanyl)-1-pyridin-2-ylprop-2-en-1-one In tetrahydrofuran for 16h; Stage #3: With ammonium acetate; acetic acid In tetrahydrofuran for 4h; Heating;	77%
With potassium tert-butylate; ammonium acetate 2) AcOH, heating; Multistep reaction;

2-acetyl-4-methylpyridine (59576-26-0) + S-benzyldithiocarbazate (13331-31-2) → C16H17N3S2 (1599471-47-2)

Conditions	Yield
In ethanol	74%

2-acetyl-4-methylpyridine (59576-26-0) + 3-(3,4,5-trimethoxyphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde → (Z)-1-(4-methylpyridin-2-yl)-3-(1-phenyl-3-(3,4,5-trimethoxyphenyl)-1H-pyrazol-4-yl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In methanol Claisen-Schmidt Condensation; Reflux;	72%

2-acetyl-4-methylpyridine (59576-26-0) → 3,5-dimethyl-[1,2,3]triazolo[1,5-a]pyridine (1384956-00-6)

Conditions	Yield
Stage #1: 2-acetyl-4-methylpyridine With hydrazine hydrate In ethanol for 1h; Reflux; Stage #2: With [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 0.5h;	70%
Multi-step reaction with 2 steps 1: methanol / Cooling with ice 2: morpholine / 90 - 100 °C View Scheme
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 1 h / Reflux 2: [bis(acetoxy)iodo]benzene / dichloromethane / 0.5 h / 20 °C View Scheme

2-acetyl-4-methylpyridine (59576-26-0) + S-(2-methylbenzyl)dithiocarbazate (34930-10-4) → C17H19N3S2

Conditions	Yield
In ethanol; acetonitrile Heating;	70%

2-acetyl-4-methylpyridine (59576-26-0) + N-(2-bromophenyl)hydrazinecarbothioamide (25688-12-4) → (E)-N-(2-bromophenyl)-2-(1-(4-methylpyridin-2-yl)ethylidene)hydrazine-1-carbothioamide

Conditions	Yield
With acetic acid In methanol for 2h; Reflux;	69%

2-acetyl-4-methylpyridine (59576-26-0) + 2,3-Dimethoxy-naphthalene-1-carbaldehyde (56252-09-6) → (E)-3-(2,3-dimethoxynaphthalen-1-yl)-1-(4-methylpyridin-2-yl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In methanol at 5 - 10℃; Inert atmosphere;	67%

pyridine (110-86-1) + 2-acetyl-4-methylpyridine (59576-26-0) → N-[(2-(4-methyl)pyridin-2'-yl)-2-oxoethyl]pyridinium iodide

Conditions	Yield
With iodine at 20℃;	65%

2-acetyl-4-methylpyridine (59576-26-0) + 4-dimethylamino-benzaldehyde (100-10-7) → (E)-3-(4-(dimethylamino)phenyl)-1-(4-methylpyridin-2-yl)prop-2-en-1-one

Conditions	Yield
With potassium hydroxide In ethanol; water at 20℃; for 3h;	62%

2-acetyl-4-methylpyridine (59576-26-0) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → 3-(dimethylamino)-1-(4-methylpyridin-2-yl)prop-2-en-1-one (166196-85-6)

Conditions	Yield
for 20h; Heating;	61%
for 3h; Reflux; Inert atmosphere; Schlenk technique;	0.6 g

2-acetyl-4-methylpyridine (59576-26-0) + 4-bromo-benzaldehyde (1122-91-4) → 1-(3-oxo-3-[2-(4-methylpyridyl)]propen-1-yl)-4-bromobenzene (878007-29-5)

Conditions	Yield
With sodium hydroxide In methanol; water at 25℃; for 1h; Claisen-Schmidt condensation;	60%

2-acetyl-4-methylpyridine (59576-26-0) + 3-dimethyl-amino-2-methylpropenal (920518-65-6) → 4,4'-dimethyl-2,2'-bipyridines (1134-35-6)

Conditions	Yield
With ammonium acetate; sodium hydroxide; acetic acid In tetrahydrofuran; toluene	59.7%

2-acetyl-4-methylpyridine (59576-26-0) + 2,5-diaminobenzenesulfonic acid sodium salt → C22H21N4O3S(1-)*Na(1+)

Conditions	Yield
In 5,5-dimethyl-1,3-cyclohexadiene; ethanol Reflux;	59%

2-acetyl-4-methylpyridine (59576-26-0) + methyl vinyl ketone (78-94-4) → 8-acetyl-1-aza-7-ethylbicyclo[4.3.0]nona-2,4,6,8-tetraene (1567389-02-9) + 8-acetyl-1-aza-7-ethyl-9-(3-oxobutyl)bicyclo[4.3.0]nona-2,4,6,8-tetraene (1567389-18-7)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In water; acetonitrile at 0℃; for 12h; Baylis-Hillman Reaction; Reflux; Overall yield = 80 %;	A 57% B 23%

2-acetyl-4-methylpyridine (59576-26-0) + m-tolyl aldehyde (620-23-5) → 4′-(3-methylphenyl)-4,4″-dimethylterpyridine

Conditions	Yield
With ammonia; potassium hydroxide In ethanol; water at 60℃; for 24h; Kroehnke Pyridine Synthesis;	51%

2-acetyl-4-methylpyridine (59576-26-0) + 2-methoxy-6-methyl-benzaldehyde (54884-55-8) → (E)-3-(2-methoxy-6-methylphenyl)-1-(pyridin-2-yl)prop-2-en-1-one

Conditions	Yield
With sodium hydroxide In ethanol at 20℃; for 1h; Inert atmosphere;	48%

2-acetyl-4-methylpyridine (59576-26-0) + 4-formylphenylboronic acid, (87199-17-5) → C23H20BN3O2

Conditions	Yield
Stage #1: 2-acetyl-4-methylpyridine; 4-formylphenylboronic acid, With sodium hydroxide In ethanol at 25℃; for 10h; Stage #2: With ammonium hydroxide In ethanol; water for 20h; Reflux;	47%

Upstream product

• 1620-76-4 2-Cyano-4-methylpyridin 
• 917-64-6 methyl magnesium iodide 
• 4926-28-7 2-Bromo-4-picoline 
• 75-16-1 methylmagnesium bromide 
• 695-34-1 2-Amino-4-methylpyridine 
• 108-89-4 picoline 
• 123-63-7 paracetaldehyde 
• 127-19-5 N,N-dimethyl acetamide 

Downstream Products

• 204701-34-8 1-{3-oxo-3-[2-(4-methylpyridyl)]propen-1-yl}-4-chlorobenzene 
• 40472-49-9 2-(4-methylpyridin-2-yl)propan-2-ol 
• 759442-78-9 2-bromo-1-(4-methylpyridin-2-yl)ethan-1-one 
• 1007-14-3 4-Methyl-picolinimidsaeurehydrazid 
• 1620-76-4 2-Cyano-4-methylpyridin 
• 1581709-76-3 4-methyl-2-(1-phenylvinyl)pyridine 

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