Isonicotinic Acid → Pyridine-4-carbonyl chloride

123 g (1 mol) of isonicotinic acid are placed in a 1 liter round-bottomed flask equipped with a condenser and a calcium chloride drying tube, and 250 ml of thionyl chloride are added all at once, whilst cooling with an ice bath. The exothermic reaction lasts about ten minutes. The mixture is then heated under reflux on an oil bath for one and a half hours. The excess thionyl chloride is driven off and the crystalline residue is taken up in 100 ml of dry diethyl ether. The mixture is stirred and the white precipitate which forms is filtered off, washed again with 50 ml of diethyl ether and dried to yield 171 g of isonicotinoyl chloride in the form of the hydrochloride. 92 g (0.516 mole) of this are placed in a 2 liter three-necked flask equipped with a thermometer, a stirrer, a condenser and a calcium chloride drying tube, and 300 ml of anhydrous toluene are added. The mixture is cooled to 10° C., 262 g (1.96 mol) of ground aluminium chloride are added in small portions and the mixture is stirred for 2 hours at ambient temperature. The dark red solution is then transferred to a dropping funnel and added dropwise to 2.5 liters of iced water cooled with an ice bath. 800 ml of ethyl acetate are then added, followed by the addition of 1 liter of sodium carbonate solution (d=1.33), with cooling. This gives a solution from which the organic phase is decanted. The aqueous phase is extracted a further three times with 500 ml of ethyl acetate, the organic phases are combined, washed with water and dried and the solvent is evaporated off in vacuo in a water bath. The residue is triturated with 100 ml of ethanol, whilst cooling in an ice bath. It is isolated by filtration and dried to give 80 g of 4-(4-methylbenzoyl)-pyridine. 42.6 ml of hydrazine hydrate and 18.4 ml of water are then added, followed by 420 ml of ethylene glycol and then by 103.5 g of sodium hydroxide pellets. The mixture is heated under reflux for 2 hours and cooled and 1 liter of water is added. The supernatant oil is extracted with diethyl ether (4×250 ml). The ether phase is washed with water, dried and evaporated. This gives 72 g of 4-(4-methylbenzyl)-pyridine in the form of an oil which crystallises.

1. customequipped with a condenser and a calcium chloride drying tube
2. temperaturewhilst cooling with an ice bath
3. customThe exothermic reaction
4. waitlasts about ten minutes
5. temperatureThe mixture is then heated
6. temperatureunder reflux on an oil bath for one and a half hours
7. filtrationthe white precipitate which forms is filtered off
8. washwashed again with 50 ml of diethyl ether
9. customdried

ORD record

ord-b0985bf15a4749a9b986476f68a93a70

Source dataset

uspto-grants-1987_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04690931