- Email: [email protected]
Environment friendly protocol for the synthesis of nitriles from aldehydes
Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 1025–1028 www.elsevier.com/locate/cclet
Environment friendly protocol for the synthesis of nitriles from aldehydes M.B. Madhusudana Reddy, M.A. Pasha * Department of Studies in Chemistry, Central College Campus, Bangalore University, Bengaluru 560001, India Received 2 December 2009
Abstract A rapid and eco-friendly one-pot protocol for the synthesis of nitriles has been developed by treating various araldehydes bearing electron withdrawing as well as electron donating groups with hydroxylamine hydrochloride in the presence of non-toxic, noncorrosive and reusable zinc oxide (ZnO) as the catalyst under solvent-free microwave irradiation. The present approach offers the advantages of a clean reaction, simple methodology, employing readily available catalyst, short reaction duration (<1 min), high selectivity; and high yield (90–98%). # 2010 M.A. Pasha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Aldehydes; Nitriles; Solvent-free; Microwave irradiation; Benign procedure
The synthesis of nitriles from aldehydes is one of the most common reactions in organic chemistry. Nitrile is a useful functional group and is an important key intermediate in organic synthesis [1]. Further, nitrile function frequently appears in pharmaceutical products; the cyano group is present in HIV protease inhibitors, 5-lipoxygenase inhibitors, and in many other bioactive molecules [2]. Nitriles also serve as useful precursors in the synthesis of carboxylic acids [3], ketones [4], amines [5], amides [6], and heterocyclic compounds [7]. Over the years, several methods have been developed for the synthesis of nitriles, which include the nucleophilic displacement of groups such as halogens, aryl sulfonates, alcohols, esters, ethers, nitro or amino and diazonium groups in the substrates with inorganic cyanide ions [8]. Other alternative methods for the synthesis of nitriles involve dehydration of amides [9] and aldoximes [10]. Conversion of aldehydes [11], alcohols [12], and carboxylic acids [13] into nitriles using various reagents and the direct conversion of amines [14] is also known. However, these methods of synthesis of nitriles suffer from some limitations such as prolonged reaction time, low yield, use of toxic solvents, requirement of excess reagents/catalysts, laborious work-up procedures, or harsh reaction conditions. Thus, the development of an alternate milder and clean procedure is highly desirable for their synthesis. Organic syntheses involving greener processes under solvent-free conditions have been investigated world wide due to stringent environment and economic regulations [15]. In this context microwave assisted reactions are significant in synthetic organic chemistry due to rapid reaction rate and ease of manipulation [16]. Simple
* Corresponding author. E-mail address: [email protected] (M.A. Pasha). 1001-8417/$ – see front matter # 2010 M.A. Pasha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2010.05.004
[(Schem_1)TD$FIG] 1026
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
Scheme 1. Synthesis of nitriles from aldehydes.
experimental procedure, high yield, improved selectivity and cleaner reaction of many microwave induced organic transformations offer additional advantages. In continuation of our work on the development of useful synthetic methodologies under different reaction conditions [17]. Herein, we are reporting a one-pot solvent-free conversion of araldehydes into the corresponding nitriles employing ZnO as catalyst under microwave irradiation (Scheme 1). ZnO is a mild and eco-friendly catalyst, easy to handle and readily available has now been used by us for the one-pot conversion of aldehydes into nitriles. 1. Experimental Araldehydes, hydroxylamine hydrochloride, ZnO and other chemicals were of commercial quality. All the reactions were carried out in a LG domestic microwave oven [Model MS-1947C/01 (230 V/320 W/2450 MHz)]. GC– Mass spectra were obtained using a Shimadzu GC-MS QP 5050A spectrometer. IR spectra were recorded on a Shimadzu FT-IR-8400s spectrophotometer as KBr pellets. A mixture of aldehyde (2 mmol), hydroxylamine hydrochloride (3 mmol) and ZnO (10 mol%) was taken in a screw capped pyrex cylindrical tube; it was homogenized and irradiated at 320 W in an unmodified domestic microwave oven. After irradiation (20–60 s), the mixture was cooled to room temperature and extracted with dichloromethane (2 5 mL). The solvent was removed under vacuum and the organic layer was dried over fused calcium chloride. The crude was chromatographed on a short column of silica gel using light petrol as eluent to get the pure product. 2. Results and discussion It was found by us that, under microwave heating, the reaction of an araldehyde with hydroxylamine hydrochloride in the presence of ZnO is fast, clean and high-yielding. To optimize the reaction conditions, we studied the reaction of 4-methoxybenzaldehyde (2 mmol) with hydroxylamine hydrochloride (3 mmol) in the presence of ZnO (10 mol%) under MWI. The starting material reacted completely within 40 s as indicated by TLC analysis. After isolation and purification by silica gel column chromatography, 4-methoxybenzonitrile was isolated in 95% yield. The selectivity of the product is also very high and found to be >90%. The effect of catalyst load on the reaction time and yield was studied. The best result was obtained with 10 mol% of the catalyst which gave 95% yield within 40 s. Use of lower amount of catalyst (<10 mol%) resulted in lower yields, but a higher amount of catalyst (>10 mol%) did not affect the reaction with respect to both duration and yield. However, in the absence of the catalyst, the yield of the nitrile was low (<10%) and oxime was a major product (>90%) after 1 min of irradiation at 320 W. We kept the amount of ZnO catalyst constant at 10 mol% and employed a wide range of solvents, polar and nonpolar, such as water, methanol, ethanol, DMF, THF, ethylacetate, diethyl ether, and hexane. This resulted in lower yields or no nitrile formation. On the other hand, the formation of the corresponding oxime (80–92%) as major product can be seen from Table 1. This study, clearly shows that MWI in conjunction with ZnO as catalyst results in high yields of nitriles under solvent-free condition. The generality of the above reaction was tested by carrying out the reactions using various substituted araldehydes, it was found that, the reactions proceed smoothly irrespective of the substituents; araldehydes having electron donating groups, e.g. –OCH3, –OH and –N,N(CH3)2 and electron withdrawing groups such as –NO2 and halides were found to give the corresponding nitriles in excellent yield (90–98%); the results of this study are presented in Table 2. This method can also be employed to an aldehyde containing a double bond (Table 2, entry q) which gave the corresponding nitrile in 90% yield. However, it is of interest to note that, the reaction of 2-furaldehyde to obtain 2-furonitrile did not occur (Table 2, entry r) even after 60 s. This may be due to the formation of a different product from 2-furaldehyde during the course of the reaction, which is not of present interest. Clearly, completion of all the reactions occurs within
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
1027
Table 1 Effect of solvents on the reaction of 4-methoxybenzaldehyde (2 mmol) with hydroxylamine hydrochloride (3 mmol) in the presence of ZnO under MWI.a. Entry
Solvent
Yield (%)
H2O CH3OH C2H5OH CH3CN DMF THF Ethylacetate Diethyl ether Hexane Solvent-free
a b c d e f g h i j a
Un-reacted aldehyde
Oxime
Nitrile
10 15 15 5 8 10 8 15 10 –
80 90 80 92 80 85 88 78 83 –
– 1 2 5 3 2 3 Not observed Not observed 94
All the reactions were conducted using 10 mol% of ZnO in 1 mL of solvent at 320 W for 1 min.
Table 2 Solvent-free synthesis of nitriles from the aldehydes under microwave irradiation at 320 W.a. Entry
Substrate (1)
Product
Time (s)
Yield (%)b
M.P or B.Pc (8C) (litt.)
a b c d e f g h i j k l m n o p q r s
Ph– 4-OMe–Ph– 3,4-(OMe)2–Ph– 3,4,5-(OMe)3–Ph– 4-OH–Ph– 3-OH–4-OMe–Ph– 4-N,N(Me)2–Ph– 4-Cl–Ph– 3-Cl–Ph– 2-Cl–Ph– 3-Cl–4-F–Ph– 3-NO2–Ph– 2-NO2–Ph– 2,4-Cl2–Ph– 4-CN–Ph– 3-CN–Ph– Ph–CH CH– 2-Furyl 2-Piperonal
3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 3q 3r 3s
35 40 22 30 25 25 35 30 35 35 60 30 40 35 50 60 40 60 40
98 95 93 96 92 90 92 95 93 90 91 93 90 92 92 91 90 – 95
185c (187) 55–56 (57–59) 60 (63) 90 (92–94) 108 (111–113) 83 (85–87) 71–73 (75–77) 90 (91–93) 93–92 (95–96) 40 (43–46) 67–69 (69–71) 112 (115) 104–106 (107–111) 55–58 (58–60) 219–220 (222) 160 (162) 263(264) – 93–94 (95)
a b c
A mixture of 2 mmol aldehyde and 3 mmol hydroxylamine hydrochloride in the presence of 10 mol% ZnO. Isolated yield. Boiling point at 690 mm/Hg.
20–60 s. The identity of the synthesized compounds was confirmed by IR spectral analysis. In the IR spectra the characteristic CN stretching mode was observed at 2220–2245 cm 1. The molecular ion peaks (M+) observed in the mass spectra were in agreement with the excepted molecular weights. The melting or boiling points of the compounds also agree with the literature values as given in Table 2. 3. Conclusion In conclusion a reasonably good, microwave assisted, rapid, one-pot synthesis of nitriles from aldehydes and hydroxylamine hydrochloride has been developed. A wide range of nitriles have been synthesized under solvent-free condition in less than 1 min. This protocol could be a practical alternative for the synthesis of nitriles, especially in difficult cases where low nucleophilicity of the aldehyde inhibits the reaction. It is also a convenient procedure for the synthesis of oximes in the presence of a suitable solvent.
1028
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
References [1] G. Tennant, in: D. Barton, D.W. Ollis, I.O. Sutherland (Eds.), Comprehensive Organic Chemistry, vol. 2, Pergamon Press, Oxford, 1979, p. 528. [2] (a) G. Lai, N.K. Bhamare, W.K. Anderson, Synlett 2 (2001) 230; (b) M.N. Janakiraman, K.D. Watenpaugh, P.K. Tomich, et al. Bioorg. Med. Chem. Lett. 8 (1998) 1237. [3] (a) X.H. Gu, X.Z. Wan, B. Jiang, Bioorg. Med. Chem. Lett. 9 (1999) 569; (b) M. Chihiro, H. Nagamoto, I. Tekemura, et al. J. Med. Chem. 38 (1995) 353. [4] G.K. Jnaneshwara, V.H. Deshpande, M. Lalithambika, et al. Tetrahedron Lett. 39 (1998) 459. [5] (a) S.J. Wittenberger, B.G. Donner, J. Org. Chem. 58 (1993) 4139; (b) T.R. Bailey, G.D. Diana, P.J. Kowalczyk, et al. J. Med. Chem. 35 (1992) 4628; (c) P.K. SKadaba, Synthesis 6 (1973) 71. [6] (a) C.J. Moody, K.J. Doyle, Prog. Heterocycl. Chem. 9 (1997) 1; (b) P.C. Ducept, S.P. Marsden, Synlett 5 (2000) 692. [7] M.E. Fabiani, Drug News Perspect. 12 (1999) 207. [8] (a) K. Friedrick, K. Wallensfels, in: Z. Rappoport (Ed.), The Chemistry of the Cyano Group, Wiley-Interscience, New York, 1970; (b) N. Kornblum, R.A. Smiley, R.K. Blackwood, et al. J. Am. Chem. Soc. 77 (1955) 6269. [9] (a) C.W. Kuo, J.L. Zhu, J.D. Wu, et al. Chem. Commun. 3 (2007) 301; (b) A. Saedny, Synthesis 2 (1985) 184, and references cited therein. [10] (a) T.A. Khan, S. Pernucheralathan, H. Ila, et al. Synlett 11 (2004) 2019; (b) M. Hosseini Sarvari, Synthesis 5 (2005) 787, and references cited therein; (c) S.H. Yang, S. Chang, Org. Lett. 3 (2001) 4209. [11] (a) N.D. Arote, D.S. Bhalerao, K.G. Akamanchi, Tetrahedron Lett. 48 (2007) 3651; (b) H. Sharghi, M. Hosseini Sarvari, Tetrahedron 58 (2002) 10323; (c) M. Carmeli, N. Shefer, S. Rozen, Tetrahedron Lett. 47 (2006) 8969; (d) B. Movassagh, S. Shokri, Tetrahedron Lett. 46 (2005) 6923; (e) E.C. Wang, G.J. Lin, Tetrahedron Lett. 39 (1998) 4047; (f) R. Ballini, D. Fiorini, A. Plamieri, Synlett 12 (2003) 1841; (g) B.P. Bandgar, S.S. Makone, Synlett 2 (2003) 262; (h) J.R. Hwu, F.F. Wong, Eur. J. Org. Chem. 11 (2006) 2513. [12] (a) F.E. Chen, Y.Y. Li, M. Xu, et al. Synthesis 13 (2002) 1804; (b) N. Iranpoor, H. Firouzabadi, B. Akhlaghinia, et al. J. Org. Chem. 69 (2004) 2562; (c) N. Mori, H. Togo, Synlett 9 (2005) 1456. [13] (a) V.J. Huber, R.A. Bartsch, Tetrahedron 54 (1998) 9281; (b) M.K. Mlinaric, R. Margeta, J. Veljkovic, Synlett 13 (2005) 2089; (c) C.O. Kangani, B.W. Day, D.E. Kelley, Tetrahedron Lett. 48 (2007) 5933; (d) V.N. Telvekar, R.A. Rane, Tetrahedron Lett. 48 (2007) 6051. [14] (a) S. Iida, H. Togo, Synlett (2007) 407, and references cited therein; (b) S. Iida, H. Togo, Synlett 16 (2006) 2633; (c) L. De luca, G. Giacomelli, Synlett 12 (2004) 2180; (d) F.E. Chen, Y.Y. Kuang, H.F. Dai, et al. Synthesis 17 (2003) 2629. [15] (a) B.M. Trost, Science 254 (1991) 1471; (b) R.A. Sheldon, Pure Appl. Chem. 72 (2000) 1233. [16] (a) A. Lew, P.O. Krutzik, M.E. Hart, et al. J. Combust. Chem. 4 (2002) 96; (b) C.O. Kappe, Angew. Chem., Int. Ed. 43 (2004) 6250. [17] (a) M.A. Pasha, M.B. Madhusudana Reddy, Synth. Commun. 39 (2009) 2928; (b) M.A. Pasha, V.P. Jayashankara, Bioorg. Med. Chem. Lett. 17 (2007) 621; (c) M.A. Pasha, V.P. Jayashankara, N.R. Swamy, Synth. Commun. 37 (2007) 1551; (d) K. Manjula, M.A. Pasha, Synth. Commun. 37 (2007) 1545.
Chinese Chemical Letters 21 (2010) 1025–1028 www.elsevier.com/locate/cclet
Environment friendly protocol for the synthesis of nitriles from aldehydes M.B. Madhusudana Reddy, M.A. Pasha * Department of Studies in Chemistry, Central College Campus, Bangalore University, Bengaluru 560001, India Received 2 December 2009
Abstract A rapid and eco-friendly one-pot protocol for the synthesis of nitriles has been developed by treating various araldehydes bearing electron withdrawing as well as electron donating groups with hydroxylamine hydrochloride in the presence of non-toxic, noncorrosive and reusable zinc oxide (ZnO) as the catalyst under solvent-free microwave irradiation. The present approach offers the advantages of a clean reaction, simple methodology, employing readily available catalyst, short reaction duration (<1 min), high selectivity; and high yield (90–98%). # 2010 M.A. Pasha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. Keywords: Aldehydes; Nitriles; Solvent-free; Microwave irradiation; Benign procedure
The synthesis of nitriles from aldehydes is one of the most common reactions in organic chemistry. Nitrile is a useful functional group and is an important key intermediate in organic synthesis [1]. Further, nitrile function frequently appears in pharmaceutical products; the cyano group is present in HIV protease inhibitors, 5-lipoxygenase inhibitors, and in many other bioactive molecules [2]. Nitriles also serve as useful precursors in the synthesis of carboxylic acids [3], ketones [4], amines [5], amides [6], and heterocyclic compounds [7]. Over the years, several methods have been developed for the synthesis of nitriles, which include the nucleophilic displacement of groups such as halogens, aryl sulfonates, alcohols, esters, ethers, nitro or amino and diazonium groups in the substrates with inorganic cyanide ions [8]. Other alternative methods for the synthesis of nitriles involve dehydration of amides [9] and aldoximes [10]. Conversion of aldehydes [11], alcohols [12], and carboxylic acids [13] into nitriles using various reagents and the direct conversion of amines [14] is also known. However, these methods of synthesis of nitriles suffer from some limitations such as prolonged reaction time, low yield, use of toxic solvents, requirement of excess reagents/catalysts, laborious work-up procedures, or harsh reaction conditions. Thus, the development of an alternate milder and clean procedure is highly desirable for their synthesis. Organic syntheses involving greener processes under solvent-free conditions have been investigated world wide due to stringent environment and economic regulations [15]. In this context microwave assisted reactions are significant in synthetic organic chemistry due to rapid reaction rate and ease of manipulation [16]. Simple
* Corresponding author. E-mail address: [email protected] (M.A. Pasha). 1001-8417/$ – see front matter # 2010 M.A. Pasha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. doi:10.1016/j.cclet.2010.05.004
[(Schem_1)TD$FIG] 1026
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
Scheme 1. Synthesis of nitriles from aldehydes.
experimental procedure, high yield, improved selectivity and cleaner reaction of many microwave induced organic transformations offer additional advantages. In continuation of our work on the development of useful synthetic methodologies under different reaction conditions [17]. Herein, we are reporting a one-pot solvent-free conversion of araldehydes into the corresponding nitriles employing ZnO as catalyst under microwave irradiation (Scheme 1). ZnO is a mild and eco-friendly catalyst, easy to handle and readily available has now been used by us for the one-pot conversion of aldehydes into nitriles. 1. Experimental Araldehydes, hydroxylamine hydrochloride, ZnO and other chemicals were of commercial quality. All the reactions were carried out in a LG domestic microwave oven [Model MS-1947C/01 (230 V/320 W/2450 MHz)]. GC– Mass spectra were obtained using a Shimadzu GC-MS QP 5050A spectrometer. IR spectra were recorded on a Shimadzu FT-IR-8400s spectrophotometer as KBr pellets. A mixture of aldehyde (2 mmol), hydroxylamine hydrochloride (3 mmol) and ZnO (10 mol%) was taken in a screw capped pyrex cylindrical tube; it was homogenized and irradiated at 320 W in an unmodified domestic microwave oven. After irradiation (20–60 s), the mixture was cooled to room temperature and extracted with dichloromethane (2 5 mL). The solvent was removed under vacuum and the organic layer was dried over fused calcium chloride. The crude was chromatographed on a short column of silica gel using light petrol as eluent to get the pure product. 2. Results and discussion It was found by us that, under microwave heating, the reaction of an araldehyde with hydroxylamine hydrochloride in the presence of ZnO is fast, clean and high-yielding. To optimize the reaction conditions, we studied the reaction of 4-methoxybenzaldehyde (2 mmol) with hydroxylamine hydrochloride (3 mmol) in the presence of ZnO (10 mol%) under MWI. The starting material reacted completely within 40 s as indicated by TLC analysis. After isolation and purification by silica gel column chromatography, 4-methoxybenzonitrile was isolated in 95% yield. The selectivity of the product is also very high and found to be >90%. The effect of catalyst load on the reaction time and yield was studied. The best result was obtained with 10 mol% of the catalyst which gave 95% yield within 40 s. Use of lower amount of catalyst (<10 mol%) resulted in lower yields, but a higher amount of catalyst (>10 mol%) did not affect the reaction with respect to both duration and yield. However, in the absence of the catalyst, the yield of the nitrile was low (<10%) and oxime was a major product (>90%) after 1 min of irradiation at 320 W. We kept the amount of ZnO catalyst constant at 10 mol% and employed a wide range of solvents, polar and nonpolar, such as water, methanol, ethanol, DMF, THF, ethylacetate, diethyl ether, and hexane. This resulted in lower yields or no nitrile formation. On the other hand, the formation of the corresponding oxime (80–92%) as major product can be seen from Table 1. This study, clearly shows that MWI in conjunction with ZnO as catalyst results in high yields of nitriles under solvent-free condition. The generality of the above reaction was tested by carrying out the reactions using various substituted araldehydes, it was found that, the reactions proceed smoothly irrespective of the substituents; araldehydes having electron donating groups, e.g. –OCH3, –OH and –N,N(CH3)2 and electron withdrawing groups such as –NO2 and halides were found to give the corresponding nitriles in excellent yield (90–98%); the results of this study are presented in Table 2. This method can also be employed to an aldehyde containing a double bond (Table 2, entry q) which gave the corresponding nitrile in 90% yield. However, it is of interest to note that, the reaction of 2-furaldehyde to obtain 2-furonitrile did not occur (Table 2, entry r) even after 60 s. This may be due to the formation of a different product from 2-furaldehyde during the course of the reaction, which is not of present interest. Clearly, completion of all the reactions occurs within
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
1027
Table 1 Effect of solvents on the reaction of 4-methoxybenzaldehyde (2 mmol) with hydroxylamine hydrochloride (3 mmol) in the presence of ZnO under MWI.a. Entry
Solvent
Yield (%)
H2O CH3OH C2H5OH CH3CN DMF THF Ethylacetate Diethyl ether Hexane Solvent-free
a b c d e f g h i j a
Un-reacted aldehyde
Oxime
Nitrile
10 15 15 5 8 10 8 15 10 –
80 90 80 92 80 85 88 78 83 –
– 1 2 5 3 2 3 Not observed Not observed 94
All the reactions were conducted using 10 mol% of ZnO in 1 mL of solvent at 320 W for 1 min.
Table 2 Solvent-free synthesis of nitriles from the aldehydes under microwave irradiation at 320 W.a. Entry
Substrate (1)
Product
Time (s)
Yield (%)b
M.P or B.Pc (8C) (litt.)
a b c d e f g h i j k l m n o p q r s
Ph– 4-OMe–Ph– 3,4-(OMe)2–Ph– 3,4,5-(OMe)3–Ph– 4-OH–Ph– 3-OH–4-OMe–Ph– 4-N,N(Me)2–Ph– 4-Cl–Ph– 3-Cl–Ph– 2-Cl–Ph– 3-Cl–4-F–Ph– 3-NO2–Ph– 2-NO2–Ph– 2,4-Cl2–Ph– 4-CN–Ph– 3-CN–Ph– Ph–CH CH– 2-Furyl 2-Piperonal
3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 3q 3r 3s
35 40 22 30 25 25 35 30 35 35 60 30 40 35 50 60 40 60 40
98 95 93 96 92 90 92 95 93 90 91 93 90 92 92 91 90 – 95
185c (187) 55–56 (57–59) 60 (63) 90 (92–94) 108 (111–113) 83 (85–87) 71–73 (75–77) 90 (91–93) 93–92 (95–96) 40 (43–46) 67–69 (69–71) 112 (115) 104–106 (107–111) 55–58 (58–60) 219–220 (222) 160 (162) 263(264) – 93–94 (95)
a b c
A mixture of 2 mmol aldehyde and 3 mmol hydroxylamine hydrochloride in the presence of 10 mol% ZnO. Isolated yield. Boiling point at 690 mm/Hg.
20–60 s. The identity of the synthesized compounds was confirmed by IR spectral analysis. In the IR spectra the characteristic CN stretching mode was observed at 2220–2245 cm 1. The molecular ion peaks (M+) observed in the mass spectra were in agreement with the excepted molecular weights. The melting or boiling points of the compounds also agree with the literature values as given in Table 2. 3. Conclusion In conclusion a reasonably good, microwave assisted, rapid, one-pot synthesis of nitriles from aldehydes and hydroxylamine hydrochloride has been developed. A wide range of nitriles have been synthesized under solvent-free condition in less than 1 min. This protocol could be a practical alternative for the synthesis of nitriles, especially in difficult cases where low nucleophilicity of the aldehyde inhibits the reaction. It is also a convenient procedure for the synthesis of oximes in the presence of a suitable solvent.
1028
M.B. Madhusudana Reddy, M.A. Pasha / Chinese Chemical Letters 21 (2010) 1025–1028
References [1] G. Tennant, in: D. Barton, D.W. Ollis, I.O. Sutherland (Eds.), Comprehensive Organic Chemistry, vol. 2, Pergamon Press, Oxford, 1979, p. 528. [2] (a) G. Lai, N.K. Bhamare, W.K. Anderson, Synlett 2 (2001) 230; (b) M.N. Janakiraman, K.D. Watenpaugh, P.K. Tomich, et al. Bioorg. Med. Chem. Lett. 8 (1998) 1237. [3] (a) X.H. Gu, X.Z. Wan, B. Jiang, Bioorg. Med. Chem. Lett. 9 (1999) 569; (b) M. Chihiro, H. Nagamoto, I. Tekemura, et al. J. Med. Chem. 38 (1995) 353. [4] G.K. Jnaneshwara, V.H. Deshpande, M. Lalithambika, et al. Tetrahedron Lett. 39 (1998) 459. [5] (a) S.J. Wittenberger, B.G. Donner, J. Org. Chem. 58 (1993) 4139; (b) T.R. Bailey, G.D. Diana, P.J. Kowalczyk, et al. J. Med. Chem. 35 (1992) 4628; (c) P.K. SKadaba, Synthesis 6 (1973) 71. [6] (a) C.J. Moody, K.J. Doyle, Prog. Heterocycl. Chem. 9 (1997) 1; (b) P.C. Ducept, S.P. Marsden, Synlett 5 (2000) 692. [7] M.E. Fabiani, Drug News Perspect. 12 (1999) 207. [8] (a) K. Friedrick, K. Wallensfels, in: Z. Rappoport (Ed.), The Chemistry of the Cyano Group, Wiley-Interscience, New York, 1970; (b) N. Kornblum, R.A. Smiley, R.K. Blackwood, et al. J. Am. Chem. Soc. 77 (1955) 6269. [9] (a) C.W. Kuo, J.L. Zhu, J.D. Wu, et al. Chem. Commun. 3 (2007) 301; (b) A. Saedny, Synthesis 2 (1985) 184, and references cited therein. [10] (a) T.A. Khan, S. Pernucheralathan, H. Ila, et al. Synlett 11 (2004) 2019; (b) M. Hosseini Sarvari, Synthesis 5 (2005) 787, and references cited therein; (c) S.H. Yang, S. Chang, Org. Lett. 3 (2001) 4209. [11] (a) N.D. Arote, D.S. Bhalerao, K.G. Akamanchi, Tetrahedron Lett. 48 (2007) 3651; (b) H. Sharghi, M. Hosseini Sarvari, Tetrahedron 58 (2002) 10323; (c) M. Carmeli, N. Shefer, S. Rozen, Tetrahedron Lett. 47 (2006) 8969; (d) B. Movassagh, S. Shokri, Tetrahedron Lett. 46 (2005) 6923; (e) E.C. Wang, G.J. Lin, Tetrahedron Lett. 39 (1998) 4047; (f) R. Ballini, D. Fiorini, A. Plamieri, Synlett 12 (2003) 1841; (g) B.P. Bandgar, S.S. Makone, Synlett 2 (2003) 262; (h) J.R. Hwu, F.F. Wong, Eur. J. Org. Chem. 11 (2006) 2513. [12] (a) F.E. Chen, Y.Y. Li, M. Xu, et al. Synthesis 13 (2002) 1804; (b) N. Iranpoor, H. Firouzabadi, B. Akhlaghinia, et al. J. Org. Chem. 69 (2004) 2562; (c) N. Mori, H. Togo, Synlett 9 (2005) 1456. [13] (a) V.J. Huber, R.A. Bartsch, Tetrahedron 54 (1998) 9281; (b) M.K. Mlinaric, R. Margeta, J. Veljkovic, Synlett 13 (2005) 2089; (c) C.O. Kangani, B.W. Day, D.E. Kelley, Tetrahedron Lett. 48 (2007) 5933; (d) V.N. Telvekar, R.A. Rane, Tetrahedron Lett. 48 (2007) 6051. [14] (a) S. Iida, H. Togo, Synlett (2007) 407, and references cited therein; (b) S. Iida, H. Togo, Synlett 16 (2006) 2633; (c) L. De luca, G. Giacomelli, Synlett 12 (2004) 2180; (d) F.E. Chen, Y.Y. Kuang, H.F. Dai, et al. Synthesis 17 (2003) 2629. [15] (a) B.M. Trost, Science 254 (1991) 1471; (b) R.A. Sheldon, Pure Appl. Chem. 72 (2000) 1233. [16] (a) A. Lew, P.O. Krutzik, M.E. Hart, et al. J. Combust. Chem. 4 (2002) 96; (b) C.O. Kappe, Angew. Chem., Int. Ed. 43 (2004) 6250. [17] (a) M.A. Pasha, M.B. Madhusudana Reddy, Synth. Commun. 39 (2009) 2928; (b) M.A. Pasha, V.P. Jayashankara, Bioorg. Med. Chem. Lett. 17 (2007) 621; (c) M.A. Pasha, V.P. Jayashankara, N.R. Swamy, Synth. Commun. 37 (2007) 1551; (d) K. Manjula, M.A. Pasha, Synth. Commun. 37 (2007) 1545.