Org. Synth. 1944, 24, 68
DOI: 10.15227/orgsyn.024.0068
4-METHYLCARBOSTYRIL
[Carbostyril, 4-methyl-]
Submitted by W. M. Lauer and C. E. Kaslow.
Checked by C. F. H. Allen and H. W. J. Cressman.
1. Procedure
One hundred seventy-seven grams (1 mole) of acetoacetanilide is added in small portions by means of a spatula to 185 ml. of concentrated sulfuric acid which has been heated previously to 75° (Note 1) in a 1-l. three-necked flask provided with a mechanical stirrer and a thermometer which extends into the liquid. The temperature of the mixture is maintained at 70–75° by intermittent cooling until nearly all the acetoacetanilide has been added. The last 10–15 g. is added without cooling, and the temperature rises to 95°; the addition requires 20–30 minutes. The heat of reaction maintains the temperature at 95° for about 15 minutes; the reaction mixture is then kept an additional 15 minutes at 95° by external heating. After the solution has cooled to 65°, it is poured into 5 l. of water with vigorous stirring.
After cooling, the product is filtered by suction, washed with four 500-ml. portions of water and two
250-ml. portions of methanol, and air-dried. The yield of
4-methylcarbostyril is
138–144 g. (
86–91%). This material, which melts at
219–221°, is suitable for preparing
2-chlorolepidine (p. 194). It may be purified further by recrystallization from
95% ethanol. For recrystallization 39 g. is dissolved in
650 ml. of solvent; the recovery is
33–33.5 g., and the melting point of the product is
222–224°.
2. Notes
1.
The reaction flask must be so situated that it can be cooled rapidly. The submitter reports that the yield was reduced to
72% in one run in which the temperature reached 120°.
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3. Discussion
The only useful method for preparing
4-methylcarbostyril is that of Knorr,
1 described by Mikhailov.
2 Two modifications include the use of
aniline and
ethyl acetoacetate, without isolation of
acetoacetanilide,
3 and the use of
boron trifluoride as a cyclization agent.
4
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
ethanol (64-17-5)
sulfuric acid (7664-93-9)
methanol (67-56-1)
aniline (62-53-3)
Ethyl acetoacetate (141-97-9)
boron trifluoride (7637-07-2)
Acetoacetanilide (102-01-2)
2-Chlorolepidine (634-47-9)
4-Methylcarbostyril,
Carbostyril, 4-methyl- (607-66-9)
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