a variety of aldehydes were successfully transformed into nitriles by treatment with iodine in ammonia water. This method is simple, economic, and environmentally benign. This method is especially useful for the transformation of water-soluble aldehydes such as carbohydrates (table 1).

The use of ammonia combined with appropriate oxidants is considered as an expedient method for the transformation of aliphatic and aromatic aldehydes to their corresponding nitriles. Indeed, six processes (methods A–F) using such an approach have been reported (Table 1). Method A is conducted by stirring an appropriate aldehyde with NH3 and O2 in MeOH using CuCl2 and MeONa as the promoters. This method provides modest yields (55–82%) of aromatic and aliphatic nitriles, but low yields (<10%) of acrylonitrile and furonitrile. Method B is performed in dry benzene by slow bubbling with NH3 gas and the portionwise addition of Pb(OAc)4 in a simultaneous manner. This procedure is tedious, and only small-scale reactions are demonstrated to give benzonitrile (68%), furonitrile (37%), and heptanenitrile (59%). Using method C, benzonitrile (50%), p-chlorobenzonitrile (68%), p-methoxybenzonitrile (50%), cinnamononitrile (10%), and heptanenitrile (26%) are obtained from their corresponding aldehydes on treating with iodine and MeONa in NH3 gas saturated MeOH solution. This method is complicated by the presence of MeONa to give some methyl esters. Method D, using elemental sulfur and NaNO2 in liquid NH3 at 100°C, is limited to the transformation of aromatic aldehydes. Method E converts aldehydes to nitriles by electrooxidation in methanolic NH3 solution containing KI and MeONa. This method fails to prepare p-nitrobenzonitrile or furonitrile due to complications from other reactions. Using method F, a mixture of aldehyde and H2O2 (50% solution) are slowly added (dropwise over 2.5–4 h) into NH3 gas saturated 2-propanol solution containing CuCl. This method is applicable to large-scale reactions (e.g. 1.5 mol) by using excessive amounts of H2O2 (e.g. 3.35 mol) with cautious cooling. Benzaldehydes and conjugated aldehydes are thus converted to the corresponding nitriles in variable yields (32–87%), as shown by the six examples. However, the reaction of enolizable aldehydes (undecanal and citronellal) is inefficient, giving the nitrile products in low yields (14 and 8%, respectively, according to the GC analyses).

On the basis of NH3/oxidant protocols,  a practical and environmentally benign method for direct transformation of aldehydes to nitriles was developed. It was found that treatment of various aldehydes with iodine (1.1 molar proportions) in ammonia water (28% solution) at room temperature for a short period afforded the desired nitriles in very high yields ( Table 1). According to the previous reports, it was speculated that the reaction proceeded via oxidation of aldimine with iodine to give an N-iodo aldimine intermediate, which eliminated an HI molecule in ammonia solution to afford the nitrile product. The aldehydes examined in this study included benzaldehydes, heterocyclic aromatic aldehydes, a,b-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% solution) and THF (1 mL) at room temperature. 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 Na2S2O3 (5 mL of 5% solution), followed by extraction with ether (2×15 mL), to give a practically pure nitrile product.

By comparison with the closely related methods C and E, the current method exhibited distinct advantages. First,  the readily available ammonia water instead of ammonia gas saturated methanol was utilized. The operation of such a reaction using our method became simple and efficient. Second,  MeONa in the reaction media was omitted so that the complication of side reactions (e.g. formation of methyl ester) found in the previous methods was avoided. In the absence of MeONa, transformation of aldehydes to nitriles still proceeded rapidly. These two small changes did improve the yields of nitriles to a great extent, especially in the preparation of p-nitrobenzaldehyde (96%), furonitrile (88%), cinnamononitrile (97%), and aliphatic nitriles (>90%). It was also noted that the method was ideal for water-soluble substrates, such as the carbohydrates shown in Eqs. (2) and (3). Thus, 2-deoxy-D-ribose was treated with I2 in ammonia water at room temperature for 30 min to give an 83% yield of (3,4,5-triacetoxy)pentanenitrile9 (13) after subsequent acetylation (Ac2O/pyridine). By a similar procedure, 2,3,4,5,6-penta-O-benzyl-D-glucose was smoothly converted to 2,3,4,5,6-penta-O-benzyl-D-glucononitrile10 (14) in 85% yield.

Reference: Tetrahedron Letters 42 (2001) 1103–1105