3-Pyridinemethanol

Manufacturing Process

The catalyst is prepared by suspending 5 kg of catalyst grade charcoal in 200 liters of water, in a pressure vessel, and adding thereto 25 liters of 4% (as Pd metal) aqueous palladous chloride. Air is displaced from the vessel and then hydrogen is passed into the aqueous mixture at a pressure of 3 to 5 psi, while stirring, until no further absorption is noted and the chloride is completely reduced to metal.To the aqueous suspension of the palladized charcoal catalyst thus obtained are added 20.8 kg of 3-cyano-pyridine (96% purity); and then are added 70 liters of a hydrochloric acid solution prepared by diluting 30 liters of 36% HCl with 40 liters of water. This represents approximately 1.75 mols of HCl for each mol of 3-cyano-pyridine. The suspension is maintained at 10° to 15°C and stirred continuously while introducing a current of hydrogen at a pressure of 3 to 5 psi. When absorption of hydrogen ceases and the 3-cyanopyridine is completely reduced, the reaction mixture is filtered to remove the catalyst. The filter cake is washed with 40 liters of water in two equal portions, and the wash water is added to the filtrate.The combined liquors, which comprise an aqueous hydrochloric acid solution of 3-aminomethyl-pyridine hydrochloride, are then heated to a temperature of 60° to 65°C, and ethyl nitrite gas is passed into the heated solution. The ethyl nitrite is generated by placing 20 liters of 90% ethyl alcohol in a suitable vessel, diluting with 200 liters of water, and, while stirring, adding to the dilute alcohol 18.3 kg of nitrosyl chloride at the rate of 2.25 kg per hour. (The process using methyl nitrite is carried out by substituting a stoichiometrically equivalent quantity of methyl alcohol for the ethyl alcohol.)When all the ethyl nitrite has been added, the reaction mixture is refluxed for approximately one hour, then concentrated to dryness under reduced pressure (25 to 30 mm Hg) and at a maximum temperature of 70°C. The crystalline residue is dissolved in 35 liters of water and adjusted to a pH of 8 to 9 by addition (with cooling and stirring) of 11 to 12 kg of caustic soda. The sodium chloride formed is filtered off, and the filter cake is washed with 20 liters of normal butyl alcohol. This wash liquid is used for the first extraction of the product from the aqueous filtrate. The filtrate is then further extracted with four successive 20-liter portions of n-butyl alcohol.All the extracts are combined and concentrated in vacuo (100°C/20 mm) to remove the n-butyl alcohol. The residue is submitted to fractionation under reduced pressure. The forerun (up to 112°C/2 to 3 mm) consists of a small amount of n-butyl alcohol and some 3-pyridylcarbinol. The main fraction, boiling at 112° to 114°C/2 to 3 mm, consists of 3-pyridylcarbinol.

Brand name

Roniacol (HoffmannLaRoche).

Therapeutic Function

Vasodilator

Synthesis Reference(s)

The Journal of Organic Chemistry, 28, p. 3261, 1963 DOI: 10.1021/jo01046a538Synthesis, p. 55, 1987

General Description

3-Pyridinemethanol, an aromatic primary alcohol, is the key moiety of many bio-active and industrially important compounds.

Flammability and Explosibility

Notclassified