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Triphenylphosphine dibromide: A useful reagent for conversion of aldoximes into nitriles
⁎Corresponding author. Tel.: +98 21 2285 3308; fax: +98 21 2285 3650. darvish@kntu.ac.ir (Fatemeh Darvish)
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Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Peer review under responsibility of King Saud University.
Abstract
A simple and convenient method for the synthesis of nitriles by dehydration of aldoximes has been developed using triphenylphosphine dibromide in acetonitrile at room temperature. A variety of aromatic and heteroaromatic aldoximes are converted into the corresponding nitriles in high yields.
Keywords
Aldoxime
Nitrile
Dehydration
Triphenylphosphine dibromide
1 Introduction
Nitriles represent an important class of organic compounds with a wide range of applications. This functional group has a key role in bioactive molecules (Romero et al., 2007; Yadav et al., 2009) and serves as a precursor for several group transformations e.g., carboxylic acids, aldehydes, amines, amide (Katritzky et al., 1995; Larock, 1999; Kukushkin and Pombeiro, 2002). Conversion of oxime into nitrile has been studied extensively in the literature (Magnus et al., 2001; Miller and Manson, 2001; Smith and March 2007). Dehydration of aldoximes to nitriles is one of the most common routes, avoiding toxic inorganic cyanide. Many methods have been developed for this conversion (Miller and Manson, 2001), the most recently reported procedures involve Pd(OAc)2/PPh3 in acetonitrile (Kim et al., 2009), Phthalic anhydride (Eng-Chi Wang et al., 2004), benzotriazole phosphonium hexafluorophosphate derivative/DBU in dichloromethane (Singh and Lakhshman, 2009), NCS/pyridine in DMF (Gucma and Golebiewski, 2008), diethylchlorophosphate in toluene (Sardarian et al., 2007), chlorosulfonic acid in toluene (Li et al., 2005), ionic liquid at 90 °C (Saha et al., 2009), and Zeolite under microwave irradiation (Heqedues et al., 2002). Each of these methods has one or more of the following drawbacks, for instance, the use of expensive and toxic catalyst, harsh reaction condition, tedious work up, and low yield. Thus, a mild and efficient method for the preparation of nitriles is in demand.
In the last decade, utilization of triphenylphosphine dibromide (TPPDB, PPh3Br2) has drawn considerable attention as a versatile reagent in organic synthesis. It has been used in various organic transformations, such as bromination of alcohols, phenols, enols, conversion of carboxylic acid derivatives into acyl bromides, (Paquette, 1995) and esters (Salome and Kahn, 2009). As the aforementioned, the TPPDB plays an important role as a versatile reagent in organic synthesis. Thus, it is of interest to examine the application of TPPDB in conversion of aldoximes into nitriles. Herein, we report a convenient and simple procedure for the conversion of various aromatic aldoximes into nitriles by inexpensive and easily accessible TPPDB (Scheme 1).
2 Results and discussion
To optimize the reaction conditions, the reaction between 3-bromobenzaldoxime, bromine, and triphenylphosphine was used as a model reaction. The effect of the molar ratio of the reactants as well as the reaction conditions on the efficiency of the dehydrating reaction was briefly examined. The best result was obtained when 1:1:1.5 of 3-bromobenzaldoxime/TPP/Br2 in CH3CN at room temperature were used in the dehydration reaction of 3-bromobenzaldoxime. The formation of the product was confirmed by a sharp band at 1740 cm−1 for C⚌O group stretching in the IR spectrum. To establish the generality and scope of the reaction, several aryl aldoximes were prepared (Furniss et al., 1986) and easily converted into the corresponding nitriles in high yields and short reaction times (Table 1).
Entry
Ar
Reaction time (min)
Yield (%)
Found
Mp (°C) reported
Ref.
1
C6H5
15
81
–
–
2
3-BrC6H4
18
93
40–41
37–40
Attanasi et al. (1983)
3
3-MeC6H4
7
85
–
–
4
4-MeC6H4
12
74
Oil
26–28
Khezri et al. (2007)
5
4-MeOC6H4
30
80
59–60
57–59
Kukhar and Pasternak (1974)
6
3-O2NC6H4
20
81
114–116
115–117
Hendrickson et al. (1976)
7
2-H2N C6H4
13
84
47
46–49
Haynes (1991)
8
2-HOC6H4
8
93
93–95
92–95
Niknam et al. (2005)
9
2-Thienyl
10
91
190–192
192
Saha et al. (2009)
10
1-Naphthyl
15
96
35–37
36–38
Olah et al. (1980)
11
10-Anthracenyl
11
96
165–167
167–168
Haynes (1991)
12
2,4-Cl2C6H3
7
94
58–60
59–62
Haynes (1991)
13
4-NCC6H4
13
90
229
224–227
Kazemi and Kiasat (2003)
14
4-(HC⚌NOH)C6H4
35
69
223–225
224–227
Kazemi and Kiasat (2003)
3 Conclusion
This method offers several advantages such as mild reaction conditions, short reaction times, high yields, and simple experimental and isolation procedures making it an efficient route to the synthesis of aromatic nitriles from the corresponding aldoximes.
4 Experimental
4.1 Chemicals and apparatus
All the chemicals were purchased from the Merck company and used as received. Melting points were determined with Electrothermal 9100 Apparatus and were uncorrected. IR Spectra were obtained on an ABB FT-IR FTLA 2000 spectrometer. 1H NMR and 13C NMR spectra were run on a Bruker DRX-300 (300 MHz and 75 MHz respectively) AVANCE instrument δ H, δ C in ppm, and J in Hz, using TMS as internal standard and CDCl3 as solvent.
4.2 General procedure for dehydration of aldoxime
Bromine (1.5 mmol) was added slowly to a mixture of aldoxime (1 mmol), triphenyl phosphine (1.0 mmol), and anhydrous potassium carbonate (3.3 mmol) in dry acetonitrile (10 ml) at room temperature. After completion of the reaction, which was confirmed by TLC (n-hexane/EtOAc, 7:3), the reaction mixture was filtered, and the solvent was removed to obtain the crude product. Purification by column chromatography afforded the pure corresponding nitrile. All products were identified by comparison of their physical and spectral data with the authentic samples.
4.3 Selected spectral data
4.3.1 Benzonitrile
IR (neat): 2223, 1596, 1493 cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.50 (m, 5H, Ph). 13C NMR (75 MHz, CDCl3): δ (ppm) = 132.8, 132.0, 129.1, 118.8, 112.2.
4.3.2 3-Methyl benzonitrile
IR (νmax, neat): 2228 (C≡N), 1586 (C⚌C arom.), 1480, 1300, 800 cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.55 (s, 1H, Ph), 7.40 (m, 3H, Ph), 2.40 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ (ppm) = 139.2, 133.6, 132.5, 129.0, 128.9, 119.0, 112.2, 21.1.
4.3.3 2,4-Dichlorobenzonitrile
Mp 58–60 °C (mp 59–62, Hendrickson et al., 1976). IR (νmax, KBr): 2228 (C≡N), 1581 (C⚌C arom.) cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.65 (d, 1H, J = 8.2 Hz), 7.50 (s, 1H. Ph), 7.35, (d, 1H, J = 8.2 Hz). 13C NMR (75 MHz, CDCl3): δ (ppm) = 140.1, 137.7, 134.6, 130.2, 127.9, 115.2, 111.8.
4.3.4 3-Bromobenzonitrile
Mp 40–41 °C (mp 37–40, Attanasi et al., 1983). IR (νmax neat): 2233 (C≡N), 1581(C⚌C arom.), 1471 cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.81 (s, 1H), 7.76 (d, 1H, J = 8.7 Hz), 7.62 (d, 1H, J = 8.4 Hz), 7.38 (t, 1H, J = 8.5 Hz). 13C NMR (75 MHz, CDCl3): δ (ppm) = 135.1, 133.7, 129.7, 129.4, 121.9, 116.3., 113.2.
4.3.5 4-Methoxybenzonitrile
Mp 59–60 °C (mp 57–59, Kukhar and Pasternak, 1974). IR (νmax, KBr): 2227 (C≡N), 1602 (C⚌C arom.), 1494 cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.60 (d, 2H, J = 8.8 Hz), 6.97 (d, 2H, J = 8.8 Hz), 3.87 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ (ppm) = 160.7, 131.8, 117.1, 112.7, 101.7, 53.5.
4.3.6 1-Cyanonaphtanlene
Oil (Olah et al., 1980). IR (νmax, CHCl3): 2223 (C≡N), 1589 (C⚌C arom.), 1509 cm−1. 1H NMR (300 MHz, CDCl3): δ (ppm) = 7.60 (d, 2H, J = 8.8 Hz), 7.5 (s, 1H, Ph), 6.97 (d, 2H, J = 8.8 Hz), 3.87 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): δ (ppm) = 160.7, 131.8, 117.1, 112.7, 101.7, 53.5.
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