TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 1103–1105
Pergamon
Direct transformation of aldehydes to nitriles using iodine in
ammonia water
Sanjay Talukdar, Jue-Liang Hsu, Tzu-Chi Chou and Jim-Min Fang*
Department of Chemistry, National Taiwan University, Taipei106, Taiwan, Republic of ChinaReceived 29 November 2000; accepted 30 November 2000
Abstract—Treatment of aromatic, heterocyclic, aliphatic, conjugated, and polyhydroxy aldehydes with iodine in ammonia water at room temperature for a short period gave the corresponding nitriles in high yields. © 2001 Elsevier Science Ltd. All rights reserved.
Formation of nitriles from the corresponding aldehydes is an important functional group transformation.1 Many methods involve the initial conversion of
alde-hydes to aldoximes, which are subjected to dehydration to give nitriles.2 Direct conversion of aldehydes into nitriles without isolation of nitrogen-containing inter-Table 1. Conversion of aldehydes to nitriles by using iodine in ammonia water
Nitrile (yield %) Yield (%) via other methodsa,b,c,d,e,f
Cosolvent
Substrate Reaction time (min)
THF 30 79a; 68b; 50c; 74d; 73e; 32f PhCHO 1 (96) 4-BrC6H4CHO THF 45 2 (95) 90b,g; 45d; 68e,g 3 (95) 20 82a; 50c; 83d; 90e; 48f THF 4-MeOC6H4CHO 4 (96) 81b; complicatede 4-O2NC6H4CHO THF 30 THF 10 4-NCC6H4CHO 5 (89) 2-Furaldehyde THF 7 6 (88) <10a; 37b; tracee 7 (97) 5 THF 2-Thiophenecarboxaldehyde 2-Pyridinecarboxaldehyde THF 15 8 (85) 9 (90) 63a,h; 59b,h; 26c,h; 66e,i; 14f,j CH3(CH2)7CHO THF 73 THF 10 c-C6H11CHO 10 (94) 48e Cinnamaldehyde THF 5 11 (96) 55a; 89b; 10c; 76f 12 (57)k 60 Et2O
Crotonaldehyde Tracea,l
30
2-Deoxy-D-ribose None 13 (83)m
None 30 14 (85)
Perbenzyl-D-glucose
aMethod A (Ref. 6a) uses NH
3/O2/CuCl2·2H2O/MeONa in MeOH. bMethod B (Ref. 6b) uses NH
3/Pb(OAc)4in dry benzene. cMethod C (Ref. 6c) uses NH
3/I2/MeONa in MeOH. dMethod D (Ref. 6d) uses NH
3/S8/NaNO2. eMethod E (Ref. 6e) uses NH
3/KI/MeONa in MeOH on electrooxidation. fMethod F (Ref. 6f) uses NH
3/H2O2/CuCl in 2-propanol. gThe yield for the reaction of 4-ClC
6H4CHO. hThe yield for the reaction of heptanenitrile. iThe yield for the reaction of octanenitrile. jThe yield for the reaction of undecanenitrile.
kCrotononitrile was the exclusive product according to the1H NMR analysis. Due to high volatility of crotononitrile, Et
2O was used as the
solvent instead of THF. The isolated yield decreased to 57% on evaporation.
lThe result for the reaction of acrylonitrile. mThe yield for the peracetylation derivative.
Keywords: aldehydes; nitriles; solvents and solvent effects.
* Corresponding author. Fax: (886-2)-2363-6359; e-mail: jmfang@mail.ch.ntu.edu.tw
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S 0 0 4 0 - 4 0 3 9 ( 0 0 ) 0 2 1 9 5 - X
CHO H H OH H OH H CH2OH CN H H OAc H OAc H CH2OAc i) I2, aq. NH3, r.t. ii) Ac2O, pyridine 13 CHO OBn H H BnO OBn H OBn H CH2OBn CN OBn H H BnO OBn H OBn H CH2OBn I2, aq. NH3, r.t. 14 C C R R O H N I2, aq. NH3, r.t. 1 R = C6H5 2 R = p-BrC6H4 3 R = p-MeOC6H4 4 R = p-O2NC6H4 5 R = p-NCC6H4 6 R = 2-furyl
7 R = 2-thienyl 8 R = 2-pyridyl 9 R = Me(CH2)7
10 R = cyclohexyl 11 R = PhCH=CH 12 R = MeCH=CH
S. Talukdar et al./Tetrahedron Letters42 (2001) 1103–1105 1104
mediates has also been explored.3 In most cases, aro-matic aldehydes are preferably converted to aroaro-matic nitriles, whereas the transformations of enolizable aliphatic aldehydes often give unsatisfactory yields of aliphatic nitriles. The problem can be somewhat cir-cumvented by using less available reagents4 (e.g. sulfi-mide) or unconventional approaches5 (e.g. microwave irradiation).
The use of ammonia combined with appropriate oxi-dants is considered as an expedient method for the transformation of aliphatic and aromatic aldehydes to their corresponding nitriles. Indeed, six processes (methods A–F)6 using such an approach have been reported (Table 1). Method A6ais 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 acryloni-trile and furoniacryloni-trile. Method B6b is performed in dry benzene by slow bubbling with NH3 gas and the por-tionwise addition of Pb(OAc)4 in a simultaneous man-ner. This procedure is tedious, and only small-scale reactions are demonstrated to give benzonitrile (68%), furonitrile (37%), and heptanenitrile (59%). Using method C,6c 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,6d using elemental sulfur and NaNO2in liquid NH3at 100°C, is limited to the transformation of aromatic aldehydes. Method E6e 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,6f a mixture of aldehyde and H
2O2 (50% solution) are slowly added (dropwise over 2.5–4 h) into NH3gas saturated 2-propanol solution contain-ing 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. Benzalde-hydes and conjugated aldeBenzalde-hydes 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 ine-fficient, giving the nitrile products in low yields (14 and 8%, respectively, according to the GC analyses).
(1)
On the basis of NH3/oxidant protocols, we wish to develop a practical and environmentally benign method for direct transformation of aldehydes to nitriles. We found that treatment of various aldehydes with iodine
(1.1 molar proportions) in ammonia water (28% solu-tion) at room temperature for a short period afforded the desired nitriles in very high yields (Eq. (1) and Table 1). According to the previous reports,6e,7 we speculated that the reaction proceeded via oxidation of aldimine with iodine to give an N-iodo aldimine inter-mediate, which eliminated an HI molecule in ammonia solution to afford the nitrile product. The aldehydes examined in this study included benzaldehydes, hetero-cyclic aromatic aldehydes, a,b-unsaturated aldehydes, aliphatic aldehydes, and saccharide aldehydes.
(2)
(3)
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.
CAUTION: It is known that iodine reacts with ammo-nia water under certain conditions to give a black powder of nitrogen triiodide monoamine (NI3·NH3).8 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.
By comparison with the closely related methods C and E, our current method exhibited distinct advantages. First, we utilized the readily available ammonia water instead of ammonia gas saturated methanol. The opera-tion of such a reacopera-tion using our method became simple and efficient. Second, we omitted MeONa in the reac-tion media so that the complicareac-tion of side reacreac-tions (e.g. formation of methyl ester) found in the previous methods was avoided. In the absence of MeONa, trans-formation of aldehydes to nitriles still proceeded rapidly according to our study. These two small changes did improve the yields of nitriles to a great extent, especially in the preparation of p-nitrobenzalde-hyde (96%), furonitrile (88%), cinnamononitrile (97%), and aliphatic nitriles (>90%). It was also noted that our method was ideal for water-soluble substrates, such as
S. Talukdar et al./Tetrahedron Letters42 (2001) 1103–1105 1105
the carbohydrates shown in Eqs. (2) and (3). Thus, 2-deoxy-D-ribose was treated with I2in 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 con-verted to 2,3,4,5,6-penta-O-benzyl-D-glucononitrile10 (14) in 85% yield.
In summary, 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 use-ful for the transformation of water-soluble aldehydes such as carbohydrates.
Acknowledgements
We thank the National Science Council for financial support. We also thank Dr. Chun-Hung Lin (Institute of Biochemistry, Academia Sinica) for helpful discus-sion and providing the sample of 2,3,4,5,6-penta-O-benzyl-D-glucose.
References
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8. Roesky, H. W.; Mo¨ckel, K. Chemical Curiosities; VCH: Weinheim, 1996; pp. 292–293. 9. (3,4,5-Triacetoxy)pentanenitrile (13): [a]25 D=+7.3 (c=2.5, CHCl3); IR (neat) 2263 cm−1; 1H NMR (300 MHz, CDCl3)d 2.02 (3 H, s), 2.09 (6 H, s), 2.65–2.81 (2 H, m), 4.13 (1 H, dd, J=12.5, 4.2 Hz), 4.29 (1 H, dd, J=12.5, 3.2 Hz), 5.17–5.22 (2 H, m);13C NMR (CDCl 3, 50 MHz) d 19.6 (CH2), 20.6 (CH3×2), 20.7 (CH3), 61.2 (CH2), 66.4 (CH), 70.4 (CH), 121.7 (C), 169.4 (C), 169.5 (C), 170.2 (C). HR-FAB-MS: calcd for C11H16NO6 (M++1) m/z
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