Direct transformation of aldehydes into nitriles using iodine in ammonia waterFrom
Tetrahedron Letters, 42, 2001, 1103-1105:
abstract:
Treatment of aromatic, heterocyclic, aliphatic, conjugated and polyhydroxy aldehydes with iodine in ammonia water at RT for a short period gave the corresponding nitriles in high yields.
Formation of nitriles from the corresponding aldehydes is an important functional group transformation. Many methods involve the initial conversion of aldehydes to aldoximes, which are subjected to dehydration to give nitriles. Direct conversion of aldehydes into nitriles without isolation of nitrogen-containing intermediates has also been explored. In most cases, aromatic aldehydes are preferably converted to aromatic nitriles, whereas the transformations of enolizable aliphatic aldehydes often give unsatisfactory yields of aliphatic nitriles. The problem can be somewhat circumvented by using less available reagents (eg sulfimide) or unconventional approaches (eg microwave irradiation).
On the basis of NH
3/oxidant protocols, we wish to develop a practical and enviromentally begign method for direct transformation of aldehydes into nitriles. We found that treatment of various aldehydes with iodine (1.1 mol proportions) in ammonia water (28% sol) at RT for a short period afforded the desired nitriles in very high yields (table 1).
According to previous reports we speculated that the reaction proceeded via oxidation of aldimine with iodine to give a N-iodo aldimine intermediate, which eliminated a HI molecule in ammonia sol. to afford the nitrile product. The aldehydes examined in this study included benzaldehydes, heterocyclic aldehydes,
alpha,
beta-unsaturated aldehydes, aliphatic aldehydes and saccharide aldehydes.
The following procedure is typical: Iodine (1.1 mmol) was added to a stirring solution of aldehyde (1 mmol) in ammonia water (10 ml of 28% sol.) and THF (1 ml) at RT. The dark solution became colorless (or light gray in some cases) after stirring for 5-73 min, an indication that the reaction was complete. The reaction mixture was charged with aqueous Na
2S
2O
3 (5 ml of a 5% sol.), followed by extraction with ether (2x15 ml), to give a practically pure nitrile product.
CAUTION: It is known that iodine reacts with ammonia water under certain conditions to give a black powder of nitrogen triiodide monoamine (NI
3.NH
3). The dry powder explodes readily by mechanical shock, heat or irradiation. Although we did not have any incidents when handling the reactants in this study, one should avoid using excess reagent.
In summary, a variety of aldehydes were succesfully transformed into nitriles by treatment with iodine in ammonia water. This method is simple, economic, and enviromentally begign. This method is especially useful for the transformation of water-soluble aldehydes such as carbohydrates.
Table 1Substrate - Cosolvent - Reaction time (min.) - Yield
PhCHO - THF - 30 - 96%
4-BrC
6H
4CHO - THF - 45 - 95%
4-MeOC
6H
4CHO - THF - 20 - 95%
4-O
2NC
6H
4CHO - THF - 30 - 96%
4-NCC
6H
4CHO - THF - 10 - 89%
2-Furaldehyde - THF - 7 - 88%
2-Thiophenecarboxaldehyde - THF - 5 - 97%
2-Pyridinecarboxaldehyde - THF - 15 - 85%
CH
3(CH
2)
7CHO - THF - 73 - 90%
t-C
6H
11CHO - THF - 10 - 94%
Cinnamaldehyde - THF - 5 - 96%
Crotonaldehyde - Et
2O - 60 - 57%
2-Deoxy-D-ribose - none - 30 - 83%
Perbenzyl-D-glucose - none - 30 - 85%
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Other than phenylacetaldehydes I don't know right away where it could be useful for, for our purposes, but it seemed such a beautiful and clean reaction, had to post it. You never know where it might come in handy.