6-Chloro-2-methyl-3-nitropyridine

6-Chloro-2-methyl-3-nitropyridine Property

Melting point:

54-58 °C

Boiling point:

200°C (rough estimate)

Density 

1.5610 (rough estimate)

refractive index 

1.5500 (estimate)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

pka

-3.26±0.10(Predicted)

form 

Powder

color 

Light beige to brown

InChI

InChI=1S/C6H5ClN2O2/c1-4-5(9(10)11)2-3-6(7)8-4/h2-3H,1H3

InChIKey

GHSRMSJVYMITDX-UHFFFAOYSA-N

SMILES

C1(C)=NC(Cl)=CC=C1[N+]([O-])=O

CAS DataBase Reference

22280-60-0(CAS DataBase Reference)

Safety

Hazard Codes 

Xn,Xi

Risk Statements 

36/37/38-20/21/22-22

Safety Statements 

36/37/39-26

Hazard Note 

Harmful

HazardClass 

IRRITANT

HS Code 

29333990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H301Toxic if swalloed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P405Store locked up.

6-Chloro-2-methyl-3-nitropyridine Chemical Properties,Usage,Production

Chemical Properties

Light yellow Cryst

Uses

6-Chloro-2-methyl-3-nitropyridine has been used as a reactant for the synthesis of fluorine-containing pyridinealdoxime derivatives as treatment of organophosphorus nerve-agent poisoning.

Preparation

A mixture of 2-oxo-5-nitro-6-methyl-1,2-dihydropyridine, phosphorous oxychloride, and phosphorous pentachloride was heated at 110° C for 2 hours, whereupon the reaction mixture was charged with an additional portion of phosphorous pentachloride and phosphorous oxychloride. The reaction was stirred for 1 hour and then poured into ice water. The brown solid was filtered and washed with cold water, to give 6-Chloro-2-methyl-3-nitropyridine (94%).

Synthesis

General procedure for the synthesis of 2-chloro-5-nitro-6-methylpyridine from 2-hydroxy-6-methyl-5-nitropyridine: 1. 2-Hydroxy-6-methyl-5-nitropyridine (500 mg, 3.24 mmol), phosphorus trichloride (POCl3, 0.5 mL) and phosphorus pentachloride (PCl5, 200 mg) were mixed and the reaction was stirred for 2 hours at 150 °C. After completion of the reaction, it was cooled to room temperature, the reaction mixture was poured into ice water and extracted with dichloromethane (DCM, 3 x 20 mL). The organic phases were combined, washed with water to pH 7, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The resulting residue was dried under reduced pressure to give 6-chloro-2-methyl-3-nitropyridine (430 mg, 78% yield) as a light brown solid. 2. 3-Ethynyl-7,7-dimethyl-7,8-dihydroquinolin-5(6H)-one (199 mg, 1.00 mmol) was mixed with 6-chloro-2-methyl-3-nitropyridine (172 mg, 1.00 mmol) in the presence of PdCl2(PPh3)2 (42 mg, 0.06 mmol), P(t-Bu)3 (16 mg , 0.08 mmol) and triethylamine (TEA, 1.5 mL) in a solution of N,N-dimethylformamide (DMF, 3 mL), and the reaction was stirred at 100 °C for 3 hours. The crude product was purified by silica gel column chromatography to afford the intermediate 7,7-dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6H)-one (80 mg, 16% yield) as a yellow solid. 3. 7,7-Dimethyl-3-((6-methyl-5-nitropyridin-2-yl)ethynyl)-7,8-dihydroquinolin-5(6H)-one (194 mg, 0.58 mmol) was dissolved in ethyl acetate (EtOAc, 10 mL) and cooled to 0°C. A concentrated aqueous hydrochloric acid solution (1 mL) of stannous chloride dihydrate (SnCl2-2H2O, 650 mg, 2.90 mmol) was slowly added. The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was poured into ice water, adjusted to pH 9-10 with 15% aqueous sodium hydroxide and extracted with ethyl acetate (EtOAc, 3 × 25 mL). The organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by preparative thin layer chromatography (silica gel, dichloromethane/ethanol, 40:1) to afford the target product 2-chloro-5-nitro-6-methylpyridine (34 mg, 19% yield). Product characterization: 1H NMR (DMSO-d6) δH: 1.05 (s, 6H), 2.29 (s, 3H), 2.59 (s, 2H), 3.03 (s, 2H), 5.51 (br s, 2H), 6.92 (d, 1H), 7.24 (d, 1H), 8.15 (s, 1H), 8.83 (s, 1H). LC/MS (M+H)+ = 306.

References

[1] Journal of Fluorine Chemistry, 2011, vol. 132, # 8, p. 541 - 547
[2] Patent: WO2012/52451, 2012, A1. Location in patent: Page/Page column 113
[3] Patent: CN105906621, 2016, A. Location in patent: Paragraph 0021
[4] Patent: WO2005/42464, 2005, A1. Location in patent: Page/Page column 33
[5] Journal of the American Chemical Society, 1952, vol. 74, p. 3828,3830