591-22-0

Basic information

• Product Name: 3,5-Lutidine
• Synonyms: 3,5-dimethyl-pyridin;pyridine,3,5-dimethyl-;Lutidine,98%;3 5-LUTIDINE STANDARD FOR GC;3,5-LUTIDINE, 98+%;3,5-DIMETHYLPYRIDINE 98+%;3,5-Dimetylpyridine;3,5-Lutidine,99%
• CAS NO: 591-22-0
• Molecular Formula: C₇H₉N
• Molecular Weight: 107.15
• EINECS: 209-708-6
• Product Categories: Pyridines derivates;Heterocyclic Compounds;Biochemistry;Reagents for Oligosaccharide Synthesis
• Mol File: 591-22-0.mol
• Article Data: 45

Chemical Properties

• Melting Point: -9 °C
• Boiling Point: 169-170 °C(lit.)
• Flash Point: 128 °F
• Appearance: Clear yellow/Liquid
• Density: 0.939 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.5 mm Hg ( 20 °C)
• Refractive Index: n20/D 1.504(lit.)
• Storage Temp.: 2-8°C
• Solubility: Sol
• PKA: 6.15(at 25℃)
• Water Solubility: 33 g/L (20 ºC)
• Sensitive: Hygroscopic
• BRN: 105682
• CAS DataBase Reference: 3,5-Lutidine(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Lutidine(591-22-0)
• EPA Substance Registry System: 3,5-Lutidine(591-22-0)

Safety Data

• Hazard Codes: Xn,F,Xi,T
• Statements: 10-20/21/22-36/37/38-41-34-23/25-21
• Safety Statements: 16-26-36-36/37-45-36/37/39
• RIDADR: UN 1993 3/PG 3
• WGK Germany: 3
• F: 8
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 591-22-0(Hazardous Substances Data)

Usage

Chemical Properties

CLEAR YELLOW LIQUID

Uses

3,5-Lutidine is a reactant used in the synthesis of phthalazine and pyrazine compounds, as well as other pharmaceuticals.

Synthesis Reference(s)

Synthesis, p. 573, 1994 DOI: 10.1055/s-1994-25526

Flammability and Explosibility

Flammable

Purification Methods

Dry 3,5-lutidine with sodium and fractionally distil it through a Todd column (p 11) packed with glass helices. Dissolve (100mL) in dilute HCl (1:4) and steam distil this until 1L of distillate is collected. Excess conc NaOH is added to the residue which is again steam distilled. The base is extracted from the distillate, using diethyl ether. The extract is dried over K2CO3, and distilled. It is then fractionally crystallised by partial freezing. The hydrochloride has m 229o(sublimes at 190-231o), and the picrate has m 242-243o(dec, from H2O), 249-250o(dec, from AcOH). [Beilstein 20 II 161, 20 III/IV 2788, 20/6 V 60.]

InChI:InChI=1/C7H9N/c1-6-3-7(2)5-8-4-6/h3-5H,1-2H3

Synthetic route

N-methyl-3,5-dimethylpyridinium iodide (22739-24-8) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With pyridine hydrochloride for 10h; Heating;	95%

N-(1-propenyl)piperidine (7182-09-4) + 1,3,5-tri-tert-butyl-1,3,5-triazacyclohexane (10560-39-1) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With toluene-4-sulfonic acid In benzene at 200℃; for 9h;	67%

formaldehyd (50-00-0) + acetaldehyde (75-07-0) → pyridine (110-86-1) + 3,5-Lutidine (591-22-0) + 3-ethylpyridine (536-78-7) + 5-ethyl-2-methyl-pyridine (104-90-5) + 3-Methylpyridine (108-99-6) + 2,5-dimethylpyridine (589-93-5)

Conditions	Yield
With diammonium phosphate at 230℃; under 26252.1 - 27752.2 Torr; for 1.5h; Product distribution; investigation of the synthesis of pyridines from mixtures aldehydes;	A 1% B 1% C 22% D 2.5% E 61% F 4%

3,5-Dimethylpyridine N-oxide (3718-65-8) + N,N-Dimethylthiocarbamoyl chloride (16420-13-6) → 3,5-Lutidine (591-22-0) + C10H14N2OS

Conditions	Yield
In acetonitrile at 81℃; for 4h;	A 54% B 35%

formaldehyd (50-00-0) + propionaldehyde (123-38-6) → pyridine (110-86-1) + α-picoline (109-06-8) + 3,5-Lutidine (591-22-0) + 3-Methylpyridine (108-99-6)

Conditions	Yield
With diammonium phosphate In ethanol; water at 234℃; under 25502 - 35252.8 Torr; for 0.6h; Yields of byproduct given;	A n/a B n/a C 47% D n/a

N-methylene-tert-butylamine (13987-61-6) + propionaldehyde (123-38-6) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With piperidine; acetic acid In toluene at 200℃; for 2h; closed pipe;	47%

3,5-Dimethylpyridine N-oxide (3718-65-8) → 3,5-Lutidine (591-22-0) + 4-bromo-3,5-dimethyl-pyridine 1-oxide (70564-92-0)

Conditions	Yield
With mercury(II) diacetate; bromine; acetic acid at 70℃; for 10h; Product distribution; Mechanism; effect of metal ions;	A 17.6% B 45.6%

3,5-Dimethylpyridine N-oxide (3718-65-8) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In dichloromethane at 31℃; for 16h; Sealed tube; Irradiation;	42%
With triphenylphosphine; N-fused tetraphenylporphyrin rhenium(VII) trioxide In dichloromethane at 23℃; for 6h;	88 % Spectr.

C14H17N2(1+)*ClH*Cl(1-) (71756-64-4) → 3,5-Lutidine (591-22-0) + C14H16N2Se

Conditions	Yield
With sodium hydrogen selenide In methanol; ethanol	A n/a B 41%

acrylaldehyde diethyl acetal (3054-95-3) → pyridine (110-86-1) + α-picoline (109-06-8) + picoline (108-89-4) + 3,5-Lutidine (591-22-0) + 3-Methylpyridine (108-99-6)

Conditions	Yield
With ammonia at 250 - 450℃; under 760.051 Torr; Reagent/catalyst; Inert atmosphere; Gas phase;	A 26.87% B n/a C n/a D n/a E 34.27%

acrylaldehyde diethyl acetal (3054-95-3) → pyridine (110-86-1) + α-picoline (109-06-8) + 3,5-Lutidine (591-22-0) + 3-Methylpyridine (108-99-6)

Conditions	Yield
With ammonia at 250 - 450℃; under 760.051 Torr; Reagent/catalyst; Inert atmosphere; Gas phase;	A 31.77% B n/a C n/a D 29.24%

3,5-bis(chloromethyl)pyridine (41711-38-0) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With methanol; palladium on activated charcoal; Lindlar's catalyst Hydrogenation;

2,4,6-trichloro-3,5-dimethyl-pyridine (98274-04-5) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With methanol; potassium acetate; palladium Hydrogenation;

formaldehyd (50-00-0) + propionaldehyde (123-38-6) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With ammonium hydroxide at 230℃;
With ammonia; aluminum oxide; silica gel 1.) 80-100 deg C, 2.) 400 deg C.; Yield given. Multistep reaction;
With ammonia; aluminum oxide; silica gel Rate constant; Kinetics; Mechanism; different catalysts;
With ammonia; zeolite Gas phase;

formaldehyde diethyl acetal (462-95-3) + propionaldehyde (123-38-6) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With aluminum oxide; ammonia at 340 - 350℃;

allyl alcohol (107-18-6) → 3,5-Lutidine (591-22-0)

Conditions	Yield
With aluminum oxide; palladium/alumina; ammonia at 310℃;

pyridine (110-86-1) + 3,5-dimethyl-N-(methoxycarbonyl)pyridinium ion (134904-02-2) → 3,5-Lutidine (591-22-0) + 1-(methoxycarbonyl)pyridinium ion (35773-79-6)

Conditions	Yield
In water at 25℃; Rate constant; pH 5.60, aqueous buffer;

3,5-Lutidine (591-22-0) + methyl iodide (74-88-4) → N-methyl-3,5-dimethylpyridinium iodide (22739-24-8)

Conditions	Yield
In dimethylsulfoxide-d6 at 20℃; for 0.75h; Schlenk technique; Inert atmosphere;	100%
In acetone at 25℃; Rate constant; pKa value;
In acetonitrile at 25℃; Rate constant;

3,5-Lutidine (591-22-0) + ethyl (2-chloroaceto)acetate (638-07-3) → 1-ethoxycarbonylacetonyl-3,5-dimethylpyridinium chloride

Conditions	Yield
at 20℃; for 24h;	100%

3,5-Lutidine (591-22-0) + [N-(trifluoromethylsulfonyl)imino][4-(trifluoromethyl)phenyl]-λ3-bromane (957188-75-9) → 3,5-dimethylpyridinium (trifluoromethanesulfonyl)imide (1099795-83-1)

Conditions	Yield
In acetonitrile at 20℃; for 0.166667h; Inert atmosphere;	100%

3,5-Lutidine (591-22-0) + ethyl bromoacetate (105-36-2) → 1-(2-ethoxy-2-oxoethyl)-3,5-dimethylpyridin-1-ium bromide (64995-40-0)

Conditions	Yield
In dimethylsulfoxide-d6 at 20℃; for 8h; Schlenk technique; Inert atmosphere;	100%

3,5-Lutidine (591-22-0) + [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2 (52462-29-0) → [Ru(p-cymene)Cl2(3,5-dimethyl pyridine)]

Conditions	Yield
In dichloromethane at 20℃; for 24h;	100%

3,5-Lutidine (591-22-0) → 3,5-dimethylpyridine hydrogen bromide (321665-87-6)

Conditions	Yield
With hydrogen bromide In diethyl ether at 2 - 5℃;	100%
With hydrogen bromide In acetic acid

3,5-Lutidine (591-22-0) + cis-[Pd(COD)(o-bromotetrafluorophenyl)2] (199588-27-7) → cis-[Pd(2-C6BrF4)2(3,5-Me2py)2] (227088-13-3)

Conditions	Yield
In dichloromethane stoich. amts., stirring for 20 min; evapn., hexane addn., washing (hexane), drying in air; elem. anal.;	99%

3,5-Lutidine (591-22-0) + silver hexafluoroantimonate + (4S,5S)-1,3-di(2-methylphenyl)-4,5-diphenylimidazolin-2-ylidene(1,5-cyclooctadiene)chlororhodium*1/2(CH3)2O → [(4S,5S)-1,3-di(2-methylphenyl)-4,5-diphenylimidazolin-2-ylidene(1,5-cyclooctadiene)(3,5-lutidine)rhodium] hexafluoroantimonate

Conditions	Yield
In dichloromethane (N2, Schlenk) CH2Cl2 was added followed by AgSbF6 to Rh-complex under a stream of N2, the amine was added to the mixt. by syringe, stirred for 1h; filtered, the solvent was removed under vac., the residue was washed with pentane and dried under vac.; elem. anal.;	99%

3,5-Lutidine (591-22-0) + (CH2)18(O(C6H4)2C5H2N(C5H4N)2)Ru(C5H5N)(NC5H2(C6H4O)CHCHC5H2(C6H2(CH3)3)N)(2+)*2PF6(1-)=C77H80N6O2RuP2F12 → (CH2)18(O(C6H4)2C5H2N(C5H4N)2)Ru(C7H9N)(NC5H2(C6H4O)CHCHC5H2(C6H2(CH3)3)N)(2+)*2PF6(1-)=C79H84N6O2RuP2F12

Conditions	Yield
In further solvent(s) soln. of Ru complex in 3,5-dimethylpyridine was heated at 140°C for 2 h in dark under Ar; heptane added; filtered; washed (heptane); recovered with acetone;	99%

3,5-Lutidine (591-22-0) + bis(allyl)calcium (35815-10-2) → 2C10H14N(1-)*Ca(2+)

Conditions	Yield
for 24h; Inert atmosphere; regioselective reaction;	99%

3,5-Lutidine (591-22-0) + dimethyl sulfate (77-78-1) → 1,3,5-trimethylpyridin-1-ium methyl sulfate

Conditions	Yield
at -10 - 60℃;	99%

3,5-Lutidine (591-22-0) + triethyloxonium fluoroborate (368-39-8) → C9H14N(1+)*BF4(1-)

Conditions	Yield
In dichloromethane at 0℃; Inert atmosphere;	99%

3,5-Lutidine (591-22-0) + copper(II) chloride hydrate → Cu(3,5-dimethylpyridine)2Cl2

Conditions	Yield
In ethanol byproducts: H2O; addn. of ligand to satd. soln. of metal halide, room temp., stirring (2 h, pptn.); filtration, washing (Et2O), drying; elem. anal.;	98.5%
With triethyl orthoformate In ethanol mixing CuCl2 with slightly less than 2 equiv. of pyridine derivative, addn. of excess of triethyl orthoformate (pptn.); filtration, washing (EtOH, Et2O), drying (vac., room temp.); elem. anal.;

3,5-Lutidine (591-22-0) → 3,5-Dimethylpyridine N-oxide (3718-65-8)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In Isopropyl acetate at 10 - 35℃; for 5.83333h; Green chemistry;	98.3%
With peracetic acid at 85℃; for 2h;	97.5%
With dihydrogen peroxide; acetic acid at 80℃; for 18h;	95%

3,5-Lutidine (591-22-0) + aqueous cadmium chloride → Cd(3,5-dimethylpyridine)2Cl2

Conditions	Yield
In ethanol byproducts: H2O; addn. of ligand to satd. soln. of metal halide, room temp., stirring (2 h, pptn.); filtration, washing (Et2O), drying; elem. anal.;	98.2%

3,5-Lutidine (591-22-0) → C7H8(2)HN

Conditions	Yield
Stage #1: 3,5-Lutidine With n-butyllithium; lithium 2-(dimethylamino)ethanolate In hexane at 0℃; for 1h; Stage #2: With deuteromethanol In hexane at -78℃; for 1h;	98%

3,5-Lutidine (591-22-0) + trimethylamine-iodoborane → {(3,5-(CH3)2-C5H3N)2BH2}I

Conditions	Yield
In not given	98%

3,5-Lutidine (591-22-0) + triethylammonium cis-dichlorobis(1,3-diphenyltriazenido)indate(III) → cis-dichloro-trans-bis(3,5-dimethylpyridine)(1,3-diphenyltriazenido)indium(III) (143672-23-5)

Conditions	Yield
In acetonitrile byproducts: C6H5NHNNC6H5; addn. of pyridine via syringe to In complex soln. under N2; immediate pptn.; stirring suspension, 1h; evapn.; washing (pentane); drying (vac.); crystn. (CH2Cl2 layered with pentane, -24°C); elem. anal.;	98%

3,5-Lutidine (591-22-0) + gallium(III) chloride → 3,5-dimethyl-pyridine-gallium-trichloride (634900-22-4)

Conditions	Yield
In diethyl ether (N2); neat ligand (1 equiv.) was added dropwise to soln. of Ga compd. inEt2O at -30°C; soln. was stirred for 2 h; concd.; cooled to -78°C overnight; filtered; dried (vac.); elem. anal.;	98%

3,5-Lutidine (591-22-0) + zinc(II)(pivalate)2(H2O)2 (1307746-75-3) → [trizinc(II)(μ3-OH)(pivalate)(μ2-κ1O:κ1O'-O2C(t-Bu))4(3,5-lutidine)3]

Conditions	Yield
In methanol soln. of C5H3NMe2 in MeOH added to soln. of Zn complex in MeOH, stirred at room temp. for 12 h; volatiles removed under vac., crystd. from n-hexane at room temp. for 3 d; elem. anal.;	98%

3,5-Lutidine (591-22-0) + MoI2(CO)3(MeCN)2 (102349-56-4) → MoI2(CO)3(3,5-Me2py)(PPh3) (117199-12-9)

Conditions	Yield
With triphenylphosphine In dichloromethane PPh3 added to a soln. of Mo-complex under a stream of N2 with stirring; after 1 min 3,5-Me2-py was added, mixture stirred for 30 min;; filtered, solvent removed in vacuo, recrystd. from CH2Cl2, elem. anal.;	97%

3,5-Lutidine (591-22-0) + 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane (25015-63-8) → 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,5-dimethyl-1,2-dihydropyridine (1345455-89-1)

Conditions	Yield
With [La(η5-C5(CH3)5)H]2 at 25 - 35℃; for 3.3h;	97%
With chloro(1,5-cyclooctadiene)rhodium(I) dimer; tricyclohexylphosphine In toluene at 50℃; for 24h; Inert atmosphere;	96%
With P(C6H11)3; chloro(1,5-cyclooctadiene)rhodium(I) dimer In toluene ligand reacted with pinacolborane in toluene at 50°C for 24 h in presence of (Rh(C8H12)Cl)2 and P(C6H11)3; treated with activated charcoal, filtered under N2, concd. in vacuo;	96%
With [La(η5-C5(CH3)5)H]2 In Cyclohexane-d12 at 35℃; for 3.3h; regiospecific reaction;	97 %Spectr.
With [Cp*(Ph2PC6H4S)Fe]2(μ-N2) In benzene-d6 at 50℃; for 24h; Inert atmosphere; regioselective reaction;	61 %Spectr.

3,5-Lutidine (591-22-0) + 1-[2-oxo-2-(4-methoxyphenyl)ethyl]-4-methoxypyridinium bromide → 1-[2-oxo-2-(4-methoxyphenyl)ethyl]-3,5-dimethylpyridinium bromide

Conditions	Yield
for 24h; Reflux;	97%

3,5-Lutidine (591-22-0) + 2-chloro-4,6-dimethoxy-1 ,3,5-triazine (3140-73-6) → 1-(4,6-dimethoxy-1,3,5-triazin-2-yl)-3,5-dimethylpyridin-1-ium chloride

Conditions	Yield
In tetrahydrofuran at 20℃; for 4h;	97%

3,5-Lutidine (591-22-0) + 1,3-bis-(5-bromo-pentyl)-benzene (960604-34-6) → 1,3-bis-[5-(3,5-dimethyl-pyridinium)-pentyl]-benzene dibromide

Conditions	Yield
In water	96%
at 60 - 70℃; for 12h;	96%

3,5-Lutidine (591-22-0) + para-bromophenacyl bromide (99-73-0) → 1-[2-(4-bromophenyl)-2-oxoethyl]-3,5-dimethylpyridinium bromide

Conditions	Yield
In ethyl acetate for 24h; Reflux;	96%
In ethyl acetate for 24h; Reflux;	96%
In ethyl acetate for 24h; Reflux;	96%

3,5-Lutidine (591-22-0) + 3'-bromomethyl-1',2'-dihydro-4'-prop-2"-ynylnaphthalene (475981-53-4) → 1-[(3",4"-dihydro-1"-prop-2"'-ynylnaphthalen-2"-yl)methyl]-3,5-dimethylpyridinium bromide

Conditions	Yield
In acetonitrile at 20℃; for 72h;	95%

3,5-Lutidine (591-22-0) + bis(2,6-di-tert-butyl-4-methylphenoxide)methylaluminum (56252-55-2) → AlCH3(OC6H2(C(CH3)3)2CH3)2(C5H3N(CH3)2)

Conditions	Yield
In pentane addn. of 3,5-dimethylpyridine to the Al compd. in pentane and stirring for 8 h; evapn. to dryness (vac.) and recrystn. from pentane/benzene; elem. anal.;	95%

Upstream product

• 107-18-6 allyl alcohol 
• 110-86-1 pyridine 
• 92670-26-3 (3,5-dimethylpyridinio)-N-phosphonate 
• 108-89-4 picoline 
• 86260-32-4 3,5-lutidine-N-sulfonate 
• 583-58-4 3,4-Lutidin 
• 119-65-3 isoquinoline 
• 17266-24-9 3,5-dimethylpyridinium picrate 
• 462-95-3 formaldehyde diethyl acetal 
• 7664-41-7 ammonia 
• 123-38-6 propionaldehyde 
• 107-11-9 1-amino-2-propene 
• 108-10-1 4-methyl-2-pentanone 
• 74-85-1 ethene 

Downstream Products

• 3222-49-9 5-methylnicotinic acid 
• 110-86-1 pyridine 
• 577-71-9 3,4-dinitophenol 
• 100-02-7 4-nitro-phenol 
• 158876-83-6 5-methyl-pyridin-3-ylmethyl chloride 
• 1832-53-7 ethyl methylphosphonic acid 
• 143798-73-6 4-chloro-3,5-dimethylpyridine 
• 74212-41-2 2-(5-methyl-pyridin-3-yl)-1-phenylethanone 
• 126294-59-5 Al(OC₆H₂(CH₃)3)3(C₅H₃N(CH₃)2) 
• 126294-56-2 Al(OC₆H₃(CH(CH₃)2)2)3(C₅H₃N(CH₃)2) 
• 155231-59-7 zinc(II)(3,5-lutidine)(tetraphenylporphyrin) 
• 143672-23-5 cis-dichloro-trans-bis(3,5-dimethylpyridine)(1,3-diphenyltriazenido)indium(III) 

Relevant articles and documents

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