Organic Syntheses, CV 6, 965
Submitted by Beng T. Ho and K. E. Walker
1.
Checked by S. Teitel, J. O'Brien, and A. Brossi.
1. Procedure
In a
1-l. Erlenmeyer flask,
25 g. (0.13 mole) of tryptamine hydrochloride (Note
1) is dissolved in 400 ml. of water by stirring and warming on a steam bath to approximately 45°. After cooling to room temperature, a solution of
13.2 g. (0.143 mole) of glyoxylic acid monohydrate (Note
2) in 30 ml. of water is added followed by the slow addition (about 3 minutes) of a cooled solution of
7.05 g. (0.126 mole) of potassium hydroxide in 35 ml. of water (Note
3). Precipitation of
tetrahydro-β-carboline-1-carboxylic acid takes place during the addition of the
potassium hydroxide solution or soon thereafter. After stirring at ambient temperature for 1 hour, the solid is collected on a filter and washed thoroughly with 100 ml. of water. The damp filter cake is transferred to a
1-l. beaker and suspended in 240 ml. of water;
34 ml. of concentrated hydrochloric acid is slowly added (Note
4) with stirring. The mixture is boiled on a hot plate for 30 minutes before an additional
35 ml. of concentrated hydrochloric acid is added. Heating is continued for another 15 minutes, and the resulting solution is allowed to cool to room temperature. The precipitated
hydrochloride salt is collected on a filter and washed with 30 ml. of water. The product is dissolved in 400 ml. of water by stirring and warming on a steam bath to approximately 55°, and the solution is adjusted to pH 12 with
20% aqueous potassium hydroxide (approximately 50 ml. is required). After cooling to room temperature, the product is collected by suction filtration, washed with 400 ml. of water, and dried in a
vacuum desiccator over
phosphorus pentoxide, yielding
17.0–17.6 g. (
78–80%) of
1,2,3,4-tetrahydro-β-carboline, m.p.
204–205° (Note
5);
1H NMR spectrum (dimethyl sulfoxide-
d6): δ 2.70 (t, 2H, C
H2CH
2N), 2.72 (s, 1H, N
H), 3.00 (t, 2H, CH
2C
H2N), 3.85 (s, 2H, CC
H2N), 6.80–7.50 (m, 4H, C
6H4), and 10.53 (s, 1H, N
H).
2. Notes
4. If all the
hydrochloric acid is added at once, foaming makes the reaction unmanageable.
5. The melting point agrees with that of the literature
2 and is unchanged on recrystallization of the product from
ethanol.
3. Discussion
The described two-step procedure is uncomplicated and can be carried out in 1 day, giving in good yield a product that does not require further purification. This procedure has been used for the preparation of
3-methyl-, 9-methyl-, and 6-methoxy-1,2,3,4-tetrahydro-β-carboline4 and has been modified for
9-phenyl-1,2,3,4-tetrahydro-β-carboline.
5 The method is generally applicable to the preparation of other 1-unsubstituted
tetrahydro-β-carbolines providing the 1-carboxylic acid precursor is soluble in the hot acid used to effect decarboxylation.
Reviews of the chemistry of the carbolines have been published.
6,7
Appendix
Compounds Referenced (Chemical Abstracts Registry Number)
3-methyl-, 9-methyl-, and 6-methoxy-1,2,3,4-tetrahydro-β-carboline
ethanol (64-17-5)
sulfuric acid (7664-93-9)
hydrochloric acid,
hydrochloride (7647-01-0)
formaldehyde (630-08-0)
potassium hydroxide (1310-58-3)
tryptamine (61-54-1)
1,2,3,4-Tetrahydro-β-carboline,
tetrahydro-β-carbolines,
1H-Pyrido[3,4-b]indole, 2,3,4,9-tetrahydro- (16502-01-5)
tryptamine hydrochloride (343-94-2)
glyoxylic acid monohydrate (6000-59-5)
1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid,
tetrahydro-β-carboline-1-carboxylic acid
9-phenyl-1,2,3,4-tetrahydro-β-carboline
phosphorus pentoxide (1314-56-3)
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