2-CHLORO-3-NITRO-4-PICOLINE

2-CHLORO-3-NITRO-4-PICOLINE - Names and Identifiers

Name	2-chloro-4-methyl-3-nitropyridine
Synonyms	2-Chloro-4-Methyl-3-NP 2-CHLORO-3-NITRO-4-PICOLINE 2-chloro-4-methyl-3-nitropyridine 2-CHLORO-4-METHYL-3-NITROPYRIDINE 2-CHLORO-3-NITRO-4-METHYLPYRIDINE 2-chloro-3-nitro-4-methylpyridine 3-Nitro-2-chloro-4-methylpyridine 2-chloro-4-methyl-3-nitro pyridine PYRIDINE, 2-CHLORO-4-METHYL-3-NITRO- 2-CHLORO-3-NITRO-4-PICOLINE (2-CHLORO-4-METHYL-3-NITROPYRIDINE)
CAS	23056-39-5
InChI	InChI=1/C6H5ClN2O2/c1-4-2-3-8-6(7)5(4)9(10)11/h2-3H,1H3

2-CHLORO-3-NITRO-4-PICOLINE - Physico-chemical Properties

Molecular Formula	C6H5ClN2O2
Molar Mass	172.57
Density	1.406±0.06 g/cm3(Predicted)
Melting Point	51-53 °C (lit.)
Boling Point	279.6±35.0 °C(Predicted)
Flash Point	>230°F
Solubility	Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
Vapor Presure	0.00673mmHg at 25°C
Appearance	Bright yellow crystal
Color	Yellow to beige
pKa	-1.80±0.10(Predicted)
Storage Condition	Keep in dark place,Sealed in dry,Room Temperature
Sensitive	Hygroscopic
Refractive Index	1.575
MDL	MFCD00012347

2-CHLORO-3-NITRO-4-PICOLINE - Risk and Safety

Risk Codes	R36/37/38 - Irritating to eyes, respiratory system and skin. R21/22 - Harmful in contact with skin and if swallowed.
Safety Description	S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S37/39 - Wear suitable gloves and eye/face protection S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection. S36 - Wear suitable protective clothing.
UN IDs	UN2811
WGK Germany	3
HS Code	29333999
Hazard Class	6.1
Packing Group	III

2-CHLORO-3-NITRO-4-PICOLINE - Reference Information

Uses

2-chloro-4-methyl-3-nitropyridine is a pharmaceutical intermediate that can be used to prepare nevirapine. Nevirapine is an anti-AIDS drug developed by Boehringer Ingelheim (BoehringerIngelheim) Company in Germany to prevent mother-to-child transmission of HIV.
nevirapine is a HIV-1 non-nuclear glycan reverse transcriptase inhibitor (Non-NucleosideReverseTranscriptaseInhibitor,NNRTI), which is directly connected to the reverse transcriptase of the HIV-1 and blocks RNA-dependent and DNA-dependent DNA polymerase activity by rupturing the catalytic end of this enzyme, thereby effectively reducing the number of viruses in the body and restoring human immune function. Nevirapine is currently one of the most widely used anti-AIDS drugs, mainly used to prevent mother-to-child virus transmission.

preparation

step 1, preparation of 3-nitro-4-methylpyridin-2-one (Ⅲ)

add 100 grams of tetrahydrofuran and 13.5 grams (0.1 moles) of ethyl 2-nitroacetate into a 500 ml four-mouth flask connected with stirring, thermometer and reflux condenser tube, 15.0 grams (0.1 moles) of 2-bromocrotonaldehyde, 0.5 grams of DBU (alkali catalyst),40-45 ℃ stirring reaction for 5 hours, cooling to 20-25 ℃, adding 30 grams of 17% ammonia water, 40-45 ℃ stirring reaction for 5 hours, cooling to 20-25 ℃, dichloromethane extraction for 3 times, 50 grams of dichloromethane each time, combined with dichloromethane phase, 10 grams of saturated sodium chloride aqueous solution washed once, distillation recovery of solvent, 14.7g 3-nitro-4-methylpyridin-2-one (Ⅲ) was obtained with 95.5% yield and 99.3% liquid phase purity, which was directly used in the next chlorination reaction.

step 2, preparation of 2-chloro -4-methyl -3-nitropyridine (iv)

to the 500 ml four-mouth flask connected with stirring, thermometer and reflux condenser tube, add 100g 1, 2-dichloroethane, 15.5g (0.1 mol) 3-nitro -4-methylpyridine -2-one (iii),25 grams of phosphorus oxychloride, 70-75 ℃, stir and react for 8 hours, cool to 20-25 ℃, slowly pour the reaction liquid into 300 grams of ice water, stir fully, and then 40% sodium hydroxide aqueous solution to neutralize the pH value It is 7-9, extract with 1, 2-dichloroethane three times, 50 grams each time, combine the organic phase, wash with 30 grams of saturated salt water, then dry with 5 grams of anhydrous sodium sulfate, spin steaming to remove the solvent, 15.9g of light yellow powder 2-chloro-4-methyl-3-nitropyridine (Ⅳ) was obtained with 91.1% yield and 99.3% liquid phase purity.

Last Update：2024-04-09 20:52:54