A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1944, 24, 28
DOI: 10.15227/orgsyn.024.0028
[Lepidine, 2-chloro-]
Submitted by C. E. Kaslow and W. M. Lauer.
Checked by C. F. H. Allen and H. W. J. Cressman.
1. Procedure
In a 500-ml. flask, to which is attached an air condenser whose open end is protected by absorbent cotton or calcium chloride in a drying tube, are mixed 119 g. (0.75 mole) of 4-methylcarbostyril (p. 580) and 138 g. (82.5 ml., 0.9 mole) of freshly distilled phosphorus oxychloride. The mixture is maintained at 80–85° in a water bath for about 15 minutes until most of the solid has dissolved, and then it is warmed carefully for an additional 15 minutes on a wire gauze until solution is complete. The hot reaction mixture is poured into 1 l. of water containing 1 kg. of cracked ice.
The 2-chlorolepidine is extracted, using two 750-ml. portions of ether (Note 1). The extract is shaken with two 200-ml. portions of water and then dried over 50 g. of potassium carbonate. After removal of the ether, the residual oil is distilled from a 200-ml. modified Claisen flask. The colorless distillate boils at 132–135°/3 mm. and weighs 118–122 g. (89–92%). The distillate is melted if necessary and poured into 250 ml. of petroleum ether (b.p. 40–50°); the solution is then chilled in a freezing mixture; the crystals are filtered by suction and dried in a vacuum desiccator over paraffin. The snow-white 2-chlorolepidine melts at 58–59° and weighs 114–118 g. (86–89%).
2. Notes
1. An additional 5–8 g. of slightly colored material can be secured by neutralizing the aqueous solution with 200 g. of sodium carbonate, extracting with 500 ml. of ether, and distilling. The total yield of distilled product then amounts to 125–130 g. (95–97%).
3. Discussion
The preparation described is based on the method of Knorr1 and has been used by Mikhailov,2 Krahler and Burger,3 and Mizuno.4 2-Chlorolepidine has also been prepared by the action of benzoyl chloride on 4-methylcarbostyril.5
This preparation is referenced from:

References and Notes
  1. Knorr, Ann., 236, 98 (1886).
  2. Mikhailov, J. Gen. Chem. U.S.S.R., 6, 511 (1936) [C. A., 30, 6372 (1936)].
  3. Krahler and Burger, J. Am. Chem. Soc., 63, 2368 (1941).
  4. Mizuno, J. Pharm. Soc. Japan, 69, 126 (1949) [C. A., 44, 1985 (1950)].
  5. Ellinger and Reisser, Ber., 42, 3338 (1909).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

petroleum ether

potassium carbonate (584-08-7)

ether (60-29-7)

sodium carbonate (497-19-8)

benzoyl chloride (98-88-4)

Phosphorus Oxychloride (21295-50-1)

Lepidine, 2-chloro- (634-47-9)

4-Methylcarbostyril (607-66-9)