(Hive Bee)
02-22-04 13:43
No 490443
(Rated as: excellent)
Chemistry and Industry, 1955, 1774:
A CONVENIENT METHOD OF PREPARARATION OF INDOLE-3-ALDEHYDE
By S. Swaminathan and S. Ranganathan
Department of Organic Chemistry, University of Madras, Madras-25, India
Snyder and co-workers1 have converted certain Mannich bases of indole and substituted indoles to the corresponding aldehydes by reacting with a solution of hexamethylenetetramine in glacial or dilute acetic acid. The same reaction has since been extended to the preparation of 7-azaindole-3-aldehyde2. One possible explanation for this conversion, suggested by the above authors, was the intermediate formation of the parent indoles by reversal of the Mannich bases and the subsequent reaction of these indoles with hexamethylenetetramine in a manner analogous to the Duff reaction3. This explanation was considered improbable in view of the finding that no indole-3-aldehyde could be obtained by reacting hexamethylenetetramine with a hot solution of indole in glacial acetic acid.
It has now been found, however, that indole-3-aldehyde can be obtained in 50% yield by carrying out the same reaction, under different conditions. A solution of indole (1.17 g.) in glacial acetic acid (3.3 ml.) was diluted with water to 5 ml. and powdered hexamethylenetetramine was added. This addition of the solution was made over a period of of one hour to a refluxing solution of hexamethylenetetramine (1.4 g.) in 66% acetic acid (5 ml.) and the reaction mixture poured into water (150 ml.). The crude product (0.95 g.)(m.p. 175-185°) which separated after cooling overnight was crystallized from hot water (150 ml.) to give material (0.7 g.) with m.p. 189-192°. There was no depression of melting point with authentic indole-3-aldehyde. The same yields were obtained when the reaction was carried out in 66% propionic or butyric acids. (See! You can use butyric acid too if you want to!
) The yield was equally satisfactory to a larger run (0.1 mole indole was used). In a similar way, 2-phenylindole was reacted with hexamethylenetetramine to give 2-phenylindole-3-aldehyde (m.p. 250-255°) in 99% yield. The procedure described bu Duff3 when applied to indole did not give any indole-3-aldehyde. The applicability of the above method for the synthesis of substituted indole-3-aldehydes is under investigation.References
1. Snyder, Swaminathan & Sims, J. Amer. Chem. Soc., 1952, 74, 5110
2. Robinson & Robinson, J. Amer. Chem. Soc., 1955, 77, 457
3. Duff, J. Chem. Soc., 1941, 547
The experimental procedure in aqueous organic acids from the ref 1, J. Amer. Chem. Soc., 1952, 74, 5110:
A solution of hexamethylenetetramine (4.20 g., 0.03 mole) and an equimolar portion of a Mannich base related to indole in 15 ml. of dilute acid was added dropwise to over a period of 50-60 minutes to a refluxing solution of hexamethylenetetramine (4.20 g., 0.03 mole) in 15 ml. of the same diluted acid. The reaction mixture was cooled, poured into 100 ml. of water and refrigerated for 24 hours. The crude indole-3-aldehyde was collected and recrystallized from hot water. Details of the individual experiments are given in Table I.
Table I.
| Mannich base | Acid | Yield (crude) / g. | Yield (pure) / g. | % | M.p. °C |
| A | 66% acetic | 2.5-2.75 | 1.8-2.0 | 39-47 | 189-192 |
| A | 66% propionic | 2.4-2.8 | 2.0-2.3 | 47-53 | 191-193 |
| A | 66% butyric | 1.1 | 0.9 | 20 | 189-192 |
| B | 66% acetic | 2.1 | 1.6 | 39 | 191-193 |
| B | 66% propionic | 2.6 | 1.9 | 49 | 189-192 |
A 3-Dimethylaminomethylindole (gramine). B 3-Diethylaminomethylindole.
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(Hive Addict)
02-29-04 04:15
No 491763
If you have access to POCl3 and DMR, try Vilsmeier-Haack. As discussed on Rh's page (various formylation procedures), yield is quantitative. I can back this statement, as it indeed gave these results for me in the past
.
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(Hive Bee)
02-29-04 08:11
No 491796
I found the article while looking if there were any preparations of the aldehyde not involving POCl3 or other such reagents, but thanks for the tip.
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