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Electrosynthesis of oxadiazoles from benzoylhydrazines
Chinese Chemical Letters 24 (2013) 780–782
Contents lists available at SciVerse ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Electrosynthesis of oxadiazoles from benzoylhydrazines Huan-Yue Ma, Zheng-Gen Zha *, Zhen-Lei Zhang, Li Meng, Zhi-Yong Wang * Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry, Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei 230026, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 22 March 2013 Received in revised form 5 May 2013 Accepted 13 May 2013 Available online 1 July 2013
A highly efficient conformation from facile benzoylhydrazines was developed under electrochemical condition. A variety of oxadiazoles were obtained with good yields by virtue of this new method. ß 2013 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Oxadiazoles Electrochemical reactions Steric effect
1. Introduction
2. Experimental
Heterocyclic compounds have received considerable interest in synthetic and medicinal chemistry over the last decade, since most of them are intermediates in organic synthesis and have significant pharmaceutical and biological activities [1]. Oxadiazoles, a major class of heterocyclic compounds, and their synthesis has attracted much attention from chemists [2–12]. A variety of methods for the synthesis of oxadiazoles have been reported. Examples include: (i) Continuous flow synthesis of 1,3,4-oxadiazoles carried out via Nacylation of 5-substituted tetrazoles under high-temperature [7]; (ii) Synthesis of 1,3,4-oxadiazoles realized by the Cu(II) catalyzed imine C–H functionalization [8]; (iii) Using hydrazide and acid halide in the present of oxides, which is the most widely applied method in the presence of oxides [9–12]. Although these methods afford good yields, many drawbacks, including high temperature, long reaction time, and expensive coupling reagents [9], limit their application in organic synthesis. Recently, our group has developed a series of electrochemical reactions [13–15]. Compared to other traditional redox reactions, electrochemical reactions are environmentally friendly, since electrons are considered green reagents [16–19]. Herein, we report a synthesis of 2,5-disubstituted-1,3,4-oxadiazoles from substituted benzoylhydrazines via anode oxidation at room temperature.
The instrument for electrolysis is dual display potentiostat (DJS292) (made in China). 1H NMR and 13C NMR were recorded on a Bruker AC-300 FT (1H: 300 MHz, 13C: 75 MHz) using TMS as internal reference. Firstly, the reaction was conducted in a simple electrochemical setup, which contained an undivided cell equipped with a pair of C–C electrodes. The mixture was electrolyzed under a constant current of 40 mA with continuous stirring at room temperature for 2 h. The desired product of 2,5-diphenyl-1,3,4-oxadiazole was obtained with a yield of 45% (Table 1, entry 1). When a current of 50 mA was employed, the product was improved with an increased yield to 50% (Table 1, entry 2). The pH of solution is very important to many kinds of reactions. So, the pH of our reaction system was modulated, and the product yield was increased after addition of base. The reaction yield increased to 55% when Na2CO3 was added (Table 1, entry 3). Encouraged by this result, various bases were studied in the reaction. Potassium hydroxide (KOH) was the most efficient base in the reaction (Table 1, entries 3–8). After investigation of bases, different reaction electrodes were also optimized. The experiments showed that the use of platinum electrodes gave the best results (Table 1, entries 8–11). Then, we optimized the current intensity and found 60 mA to be the best constant current for this reaction (Table 1, entries 11–14). Different electrolytes were also examined; KI turned out to be the best electrolyte. Finally, different solvents were tested. It was found that MeOH was the best choice (Table 1, entries 15–17). As a result, we established the standard reaction conditions: KOH as the base, platinum as the anode and cathode, KI as the electrolyte, and 60 mA as the reaction electrolytic current.
* Corresponding authors. E-mail addresses: [email protected] (Z.-G. Zha), [email protected] (Z.-Y. Wang).
1001-8417/$ – see front matter ß 2013 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. http://dx.doi.org/10.1016/j.cclet.2013.05.032
H.-Y. Ma et al. / Chinese Chemical Letters 24 (2013) 780–782
781
Table 1 One-pot synthesis of 2,5-diphenyl-1,3,4-oxadiazole from benzoylhydrazine under various conditions.a [TD$INLE]
HN
N N
NH2
KI, base
O
O
stirring, r.t., 2 h
Entry
Base
Anode
Cathode
Solvent
Current (mA)
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
– – Na2CO3 K2CO3 KO-t-Bu Ca(OH)2 NaOH KOH KOH KOH KOH KOH KOH KOH KOH KOH KOH
C C C C C C C C Pt C Pt Pt Pt Pt Pt Pt Pt
C C C C C C C C C Pt Pt Pt Pt Pt Pt Pt Pt
MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH:H2Oc EtOH MeOH:THFd
40 50 40 40 40 40 40 40 40 40 40 50 60 70 60 60 60
45 50 55 57 58 53 62 64 66 60 69 72 78 76 0 53 62
a
b c d
Reaction conditions: a mixture of benzoylhydrazine (0.5 mmol), KI (1 mmol) and solvent was electrolyzed at a constant current for two hours in an undivided cell, which equipped with two electrode system in room temperature. Isolated yields are given. MeOH:H2O = 0:10–9:1 are both tried, no product obtained. MeOH:THF = 0:10–9:1, the best result turned out to be 62%.
3. Results and discussion Under the optimized conditions, various substituted benzoylhydrazines were studied as shown in Table 2. When the benzoylhydrazine was electrolyzed in the optimal conditions, the desired product was obtained with a yield of 78%. Aromatic benzoylhydrazine with either electron-donating or electronwithdrawing groups on the phenyl ring worked well in the reaction to give the corresponding products with moderate to good yields. This implied that the electronic effect had little influence on the reaction. On the other hand, steric effects played a crucial role in this reaction. For instance, a fluorine substituent at the para position gave a yield of 77%, better than that when the fluorine was located at the ortho position. When 2,6-difluorobenzohydrazide was employed in this reaction, only a trace amount of oxadiazole
was obtained (Table 2, entries 5, 9, 18). In addition, heterocyclichydrazides were also employed in this reaction. While thiophene2-carbohydrazide and furan-2-carbohydrazide were used as the reaction substrates, the corresponding oxadiazoles were obtained with moderate yields (Table 2, entries 15, 16, respectively). Nevertheless, aliphatic hydrazide did not work in this reaction to give the corresponding oxadiazole (Table 2, entry 19). When acetohydrazide was used as the starting material, no oxadiazole product was obtained either. We also investigated the reaction mechanism. In terms of the experimental results, methanol played an important role in this reaction. Without pure methanol, we could not get 2,5-diphenyl1,3,4-oxadiazole. Even a 9:1 ratio of methanol and water failed to yield the desired product (Table 1, entry 15). When N0 benzylidenebenzohydrazide was used as the start material for
Table 2 Results of electrosynthesis of 2,5-disubstituted-1,3,4-oxadiazoles from substituted benzoylhydrazinea [TD$INLE]
O 2
Ar
N H
NH2
KI, KOH, MeOH 60 mA, r.t. Ar
N N O 2a-2s
Ar
Entry
R
Yield (%)b
Entry
R
Yield (%)b
Entry
R
Yield (%)b
1 2 3 4 5 6 7
Ph4-Me-C6H43-Me-C6H42-Me-C6H44-F-C6H44-Cl-C6H44-Br-C6H4-
78 76 74 62 77 75 73
8 9 10 11 12 13
4-I-C6H42-F-C6H42-Cl-C6H42-Br-C6H42-I-C6H44-MeO-C6H4-
71 66 64 60 58 74
14 15 16 17 18 19
4-CF3-C6H42-thienyl2-furyl2-naphthyl2,6-difluoro-C6H32-phenylethyl-
73 54 47 79 Trace -
a
b
Reaction conditions: a mixture of benzoylhydrazine (0.5 mmol), KI (1 mmol), KOH (3 mmol) and MeOH (10 mL) was electrolyzed at a constant current of 60 mA for two hours in an undivided cell which was equipped with a two-electrode system at room temperature. Further details in the Supporting information. Isolated yields are given.
[(Schem_1)TD$FIG]
H.-Y. Ma et al. / Chinese Chemical Letters 24 (2013) 780–782
782
O
HI Ph I
-e
I
2
Acknowledgment
N
NH2
N 1 H
Ph
N H
N
Ph
NH2 O
Ph
O
Ph
Ph
N
N
5
Ph
O
Ph 4
MeO O
N
O
H
N N
Ph
NH
Appendix A. Supplementary data
I
O MeOH
Ph
We thank the National Natural Science Foundation of China (Nos. 91213303, 21272222, 20932002, 21172205) for the financial support.
O
O Ph
I
N
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2013.05.032.
N References
3 N2
Ph
2e-
Ph
O
Ph
N N
Scheme 1. Proposed mechanism for oxidation of oxadiazoles.
electrolyzing, the product 2,5-diphenyl-1,3,4-oxadiazoles was obtained in 87% yield. All these results implied that N0 benzylidenebenzohydrazide should be the key intermediate of the reaction. Based on the results, we proposed a reaction pathway as shown in Scheme 1. Firstly, an iodine anion is oxidized to an iodine radical, which subsequently takes a hydrogen atom from benzoylhydrazine to generate the radical 2, which is unstable and further reacts with other iodine radicals in the next two steps to generate radical 3 [20]. With the release of molecular nitrogen, radical 3 would turn into benzaldehyde radical 4, which can easily take a hydrogen atom from the solvent, MeOH, to generate benzaldehyde. Benzoylhydrazine reacts with benzaldehyde to give N0 -benzylidenebenzohydrazide, which turns into 5 in an alkaline environment. After oxidation, the final product can be obtained. 4. Conclusion In conclusion, an efficient electrosynthesis of oxadiazoles from benzoylhydrazine was realized via an anode oxidation. This method could be a better way to synthesize oxadiazoles due to the mild conditions, cheap oxidant, and environmental friendliness. Therefore, a high efficiency and environmentally friendly route to synthesizing oxadiazoles was developed. Further investigations to expand the application of electrochemistry in organic synthesis are underway in our laboratory.
[1] J. Bostro¨m, A. Hogner, A. Llina`s, E. Wellner, A.T. Plowright, Oxadiazoles in medicinal chemistry, J. Med. Chem. 55 (2012) 1817–1830. [2] A. Rauf, S. Sharma, S. Gangal, One-pot synthesis, antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles, Chin. Chem. Lett. 19 (2008) 5–8. [3] S. Rostamizadeh, S. Ghamkhar, A mild and facile method for one pot synthesis of 2,5-di-substituted-1,3,4-oxadiazoles at room temperature, Chin. Chem. Lett. 19 (2008) 639–642. [4] N. Montazeri, K. Rad-Moghadam, An expeditious and one-pot synthesis of unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles under microwave irradiation and solvent-free conditions, Chin. Chem. Lett. 19 (2008) 1143–1146. [5] D.Q. Long, D.J. Li, W.Q. Cai, S.S. Chen, Synthesis and fungicidal activities of 2alkylthio-5-(3,4,5-tribenzyloxyphenyl)-1,3,4-oxadiazoles, Chin. Chem. Lett. 17 (2006) 1427–1430. [6] A. Saeed, A. Mumtaz, Solvent-free synthesis of some new 2-(3,5-dimethoxy-4methylphenyl)-5-aryl-1,3,4-oxadiazoles, Chin. Chem. Lett. 19 (2008) 423–427. [7] B. Reichart, C.O. Kappe, High-temperature continuous flow synthesis of 1,3,4oxadiazoles via N-acylation of 5-substituted tetrazoles, Tetrahedron Lett. 53 (2012) 952–955. [8] S. Guin, T. Ghosh, S.K. Rout, A. Banerjee, B.K. Patel, Cu(II) catalyzed imine C–H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles, Org. Lett. 13 (2011) 5976–5979. [9] C.O. Kangani, D.E. Kelley, B.W. Day, One pot direct synthesis of oxazolines, benzoxazoles, and oxadiazoles from carboxylic acids using the deoxo-fluor reagent, Tetrahedron Lett. 47 (2006) 6497–6499. [10] M. Kidwai, D. Bhatnagar, N.K. Mishra, Polyethylene glycol (PEG) mediated green synthesis of 2,5-disubstituted 1,3,4-oxadiazoles catalyzed by ceric ammonium nitrate (CAN), Green Chem. Lett. Rev. 3 (2010) 55–59. [11] F. Bentiss, M. Lagrene´e, D. Barbry, Rapid synthesis of 2,5-disubstituted 1,3,4oxadiazoles under microwave irradiation, Syn. Commun. 31 (2001) 935–938. [12] S.H. Mashraqui, S.G. Ghadigaonkarm, R.S. Kenny, An expeditious and convenient one pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles, Syn. Commun. 33 (2003) 2541–2545. [13] L. Zhang, H. Chen, Z.G. Zha, Z.Y. Wang, Electrochemical tandem synthesis of oximes from alcohols using KNO3 as the nitrogen source, mediated by tin microspheres in aqueous medium, Chem. Commun. 48 (2012) 6574–6576. [14] L. Zhang, J.H. Su, S.J. Wang, et al., Direct electrochemical imidation of aliphatic amines via anodic oxidation, Chem. Commun. 47 (2011) 5488–5490. [15] L. Zhang, Z.G. Zha, Z.L. Zhang, Y.F. Li, Z.Y. Wang, An electrochemical tandem reaction: one-pot synthesis of homoallylic alcohols from alcohols in aqueous media, Chem. Commun. 46 (2010) 7196–7198. [16] K. Rajeshwar, J.G. Ibanez, Environmental Electrochemistry – Fundamentals and Applications in Pollution Abatement, Academic Press, San Diego, 1997. [17] H. Lund, O. Hammerich, Organic Electrochemistry, 4th ed., Marcel Dekker, New York, 2001. [18] J. Grimshaw, Electrochemical Reactions and Mechanisms in Organic Chemistry, Elsevier, Amsterdam, 2000. [19] A.J. Bard, L.R. Faulkner, Electrochemical Methods: Fundamentals and Applications, Wiley-VCH, USA, 2003. [20] X.Q. Li, X.S. Xu, C. Zhou, Tetrabutylammonium iodide catalyzed allylic sulfonylation of a-methyl styrene derivatives with sulfonylhydrazides, Chem. Commun. 48 (2012) 12240–12250.
Contents lists available at SciVerse ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Electrosynthesis of oxadiazoles from benzoylhydrazines Huan-Yue Ma, Zheng-Gen Zha *, Zhen-Lei Zhang, Li Meng, Zhi-Yong Wang * Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry, Hefei National Laboratory for Physical Sciences at Microscale and Department of Modern Physics, University of Science and Technology of China, Hefei 230026, China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 22 March 2013 Received in revised form 5 May 2013 Accepted 13 May 2013 Available online 1 July 2013
A highly efficient conformation from facile benzoylhydrazines was developed under electrochemical condition. A variety of oxadiazoles were obtained with good yields by virtue of this new method. ß 2013 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Oxadiazoles Electrochemical reactions Steric effect
1. Introduction
2. Experimental
Heterocyclic compounds have received considerable interest in synthetic and medicinal chemistry over the last decade, since most of them are intermediates in organic synthesis and have significant pharmaceutical and biological activities [1]. Oxadiazoles, a major class of heterocyclic compounds, and their synthesis has attracted much attention from chemists [2–12]. A variety of methods for the synthesis of oxadiazoles have been reported. Examples include: (i) Continuous flow synthesis of 1,3,4-oxadiazoles carried out via Nacylation of 5-substituted tetrazoles under high-temperature [7]; (ii) Synthesis of 1,3,4-oxadiazoles realized by the Cu(II) catalyzed imine C–H functionalization [8]; (iii) Using hydrazide and acid halide in the present of oxides, which is the most widely applied method in the presence of oxides [9–12]. Although these methods afford good yields, many drawbacks, including high temperature, long reaction time, and expensive coupling reagents [9], limit their application in organic synthesis. Recently, our group has developed a series of electrochemical reactions [13–15]. Compared to other traditional redox reactions, electrochemical reactions are environmentally friendly, since electrons are considered green reagents [16–19]. Herein, we report a synthesis of 2,5-disubstituted-1,3,4-oxadiazoles from substituted benzoylhydrazines via anode oxidation at room temperature.
The instrument for electrolysis is dual display potentiostat (DJS292) (made in China). 1H NMR and 13C NMR were recorded on a Bruker AC-300 FT (1H: 300 MHz, 13C: 75 MHz) using TMS as internal reference. Firstly, the reaction was conducted in a simple electrochemical setup, which contained an undivided cell equipped with a pair of C–C electrodes. The mixture was electrolyzed under a constant current of 40 mA with continuous stirring at room temperature for 2 h. The desired product of 2,5-diphenyl-1,3,4-oxadiazole was obtained with a yield of 45% (Table 1, entry 1). When a current of 50 mA was employed, the product was improved with an increased yield to 50% (Table 1, entry 2). The pH of solution is very important to many kinds of reactions. So, the pH of our reaction system was modulated, and the product yield was increased after addition of base. The reaction yield increased to 55% when Na2CO3 was added (Table 1, entry 3). Encouraged by this result, various bases were studied in the reaction. Potassium hydroxide (KOH) was the most efficient base in the reaction (Table 1, entries 3–8). After investigation of bases, different reaction electrodes were also optimized. The experiments showed that the use of platinum electrodes gave the best results (Table 1, entries 8–11). Then, we optimized the current intensity and found 60 mA to be the best constant current for this reaction (Table 1, entries 11–14). Different electrolytes were also examined; KI turned out to be the best electrolyte. Finally, different solvents were tested. It was found that MeOH was the best choice (Table 1, entries 15–17). As a result, we established the standard reaction conditions: KOH as the base, platinum as the anode and cathode, KI as the electrolyte, and 60 mA as the reaction electrolytic current.
* Corresponding authors. E-mail addresses: [email protected] (Z.-G. Zha), [email protected] (Z.-Y. Wang).
1001-8417/$ – see front matter ß 2013 Zheng-Gen Zha. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved. http://dx.doi.org/10.1016/j.cclet.2013.05.032
H.-Y. Ma et al. / Chinese Chemical Letters 24 (2013) 780–782
781
Table 1 One-pot synthesis of 2,5-diphenyl-1,3,4-oxadiazole from benzoylhydrazine under various conditions.a [TD$INLE]
HN
N N
NH2
KI, base
O
O
stirring, r.t., 2 h
Entry
Base
Anode
Cathode
Solvent
Current (mA)
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
– – Na2CO3 K2CO3 KO-t-Bu Ca(OH)2 NaOH KOH KOH KOH KOH KOH KOH KOH KOH KOH KOH
C C C C C C C C Pt C Pt Pt Pt Pt Pt Pt Pt
C C C C C C C C C Pt Pt Pt Pt Pt Pt Pt Pt
MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH MeOH:H2Oc EtOH MeOH:THFd
40 50 40 40 40 40 40 40 40 40 40 50 60 70 60 60 60
45 50 55 57 58 53 62 64 66 60 69 72 78 76 0 53 62
a
b c d
Reaction conditions: a mixture of benzoylhydrazine (0.5 mmol), KI (1 mmol) and solvent was electrolyzed at a constant current for two hours in an undivided cell, which equipped with two electrode system in room temperature. Isolated yields are given. MeOH:H2O = 0:10–9:1 are both tried, no product obtained. MeOH:THF = 0:10–9:1, the best result turned out to be 62%.
3. Results and discussion Under the optimized conditions, various substituted benzoylhydrazines were studied as shown in Table 2. When the benzoylhydrazine was electrolyzed in the optimal conditions, the desired product was obtained with a yield of 78%. Aromatic benzoylhydrazine with either electron-donating or electronwithdrawing groups on the phenyl ring worked well in the reaction to give the corresponding products with moderate to good yields. This implied that the electronic effect had little influence on the reaction. On the other hand, steric effects played a crucial role in this reaction. For instance, a fluorine substituent at the para position gave a yield of 77%, better than that when the fluorine was located at the ortho position. When 2,6-difluorobenzohydrazide was employed in this reaction, only a trace amount of oxadiazole
was obtained (Table 2, entries 5, 9, 18). In addition, heterocyclichydrazides were also employed in this reaction. While thiophene2-carbohydrazide and furan-2-carbohydrazide were used as the reaction substrates, the corresponding oxadiazoles were obtained with moderate yields (Table 2, entries 15, 16, respectively). Nevertheless, aliphatic hydrazide did not work in this reaction to give the corresponding oxadiazole (Table 2, entry 19). When acetohydrazide was used as the starting material, no oxadiazole product was obtained either. We also investigated the reaction mechanism. In terms of the experimental results, methanol played an important role in this reaction. Without pure methanol, we could not get 2,5-diphenyl1,3,4-oxadiazole. Even a 9:1 ratio of methanol and water failed to yield the desired product (Table 1, entry 15). When N0 benzylidenebenzohydrazide was used as the start material for
Table 2 Results of electrosynthesis of 2,5-disubstituted-1,3,4-oxadiazoles from substituted benzoylhydrazinea [TD$INLE]
O 2
Ar
N H
NH2
KI, KOH, MeOH 60 mA, r.t. Ar
N N O 2a-2s
Ar
Entry
R
Yield (%)b
Entry
R
Yield (%)b
Entry
R
Yield (%)b
1 2 3 4 5 6 7
Ph4-Me-C6H43-Me-C6H42-Me-C6H44-F-C6H44-Cl-C6H44-Br-C6H4-
78 76 74 62 77 75 73
8 9 10 11 12 13
4-I-C6H42-F-C6H42-Cl-C6H42-Br-C6H42-I-C6H44-MeO-C6H4-
71 66 64 60 58 74
14 15 16 17 18 19
4-CF3-C6H42-thienyl2-furyl2-naphthyl2,6-difluoro-C6H32-phenylethyl-
73 54 47 79 Trace -
a
b
Reaction conditions: a mixture of benzoylhydrazine (0.5 mmol), KI (1 mmol), KOH (3 mmol) and MeOH (10 mL) was electrolyzed at a constant current of 60 mA for two hours in an undivided cell which was equipped with a two-electrode system at room temperature. Further details in the Supporting information. Isolated yields are given.
[(Schem_1)TD$FIG]
H.-Y. Ma et al. / Chinese Chemical Letters 24 (2013) 780–782
782
O
HI Ph I
-e
I
2
Acknowledgment
N
NH2
N 1 H
Ph
N H
N
Ph
NH2 O
Ph
O
Ph
Ph
N
N
5
Ph
O
Ph 4
MeO O
N
O
H
N N
Ph
NH
Appendix A. Supplementary data
I
O MeOH
Ph
We thank the National Natural Science Foundation of China (Nos. 91213303, 21272222, 20932002, 21172205) for the financial support.
O
O Ph
I
N
Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2013.05.032.
N References
3 N2
Ph
2e-
Ph
O
Ph
N N
Scheme 1. Proposed mechanism for oxidation of oxadiazoles.
electrolyzing, the product 2,5-diphenyl-1,3,4-oxadiazoles was obtained in 87% yield. All these results implied that N0 benzylidenebenzohydrazide should be the key intermediate of the reaction. Based on the results, we proposed a reaction pathway as shown in Scheme 1. Firstly, an iodine anion is oxidized to an iodine radical, which subsequently takes a hydrogen atom from benzoylhydrazine to generate the radical 2, which is unstable and further reacts with other iodine radicals in the next two steps to generate radical 3 [20]. With the release of molecular nitrogen, radical 3 would turn into benzaldehyde radical 4, which can easily take a hydrogen atom from the solvent, MeOH, to generate benzaldehyde. Benzoylhydrazine reacts with benzaldehyde to give N0 -benzylidenebenzohydrazide, which turns into 5 in an alkaline environment. After oxidation, the final product can be obtained. 4. Conclusion In conclusion, an efficient electrosynthesis of oxadiazoles from benzoylhydrazine was realized via an anode oxidation. This method could be a better way to synthesize oxadiazoles due to the mild conditions, cheap oxidant, and environmental friendliness. Therefore, a high efficiency and environmentally friendly route to synthesizing oxadiazoles was developed. Further investigations to expand the application of electrochemistry in organic synthesis are underway in our laboratory.
[1] J. Bostro¨m, A. Hogner, A. Llina`s, E. Wellner, A.T. Plowright, Oxadiazoles in medicinal chemistry, J. Med. Chem. 55 (2012) 1817–1830. [2] A. Rauf, S. Sharma, S. Gangal, One-pot synthesis, antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles, Chin. Chem. Lett. 19 (2008) 5–8. [3] S. Rostamizadeh, S. Ghamkhar, A mild and facile method for one pot synthesis of 2,5-di-substituted-1,3,4-oxadiazoles at room temperature, Chin. Chem. Lett. 19 (2008) 639–642. [4] N. Montazeri, K. Rad-Moghadam, An expeditious and one-pot synthesis of unsymmetrical 2,5-disubstituted-1,3,4-oxadiazoles under microwave irradiation and solvent-free conditions, Chin. Chem. Lett. 19 (2008) 1143–1146. [5] D.Q. Long, D.J. Li, W.Q. Cai, S.S. Chen, Synthesis and fungicidal activities of 2alkylthio-5-(3,4,5-tribenzyloxyphenyl)-1,3,4-oxadiazoles, Chin. Chem. Lett. 17 (2006) 1427–1430. [6] A. Saeed, A. Mumtaz, Solvent-free synthesis of some new 2-(3,5-dimethoxy-4methylphenyl)-5-aryl-1,3,4-oxadiazoles, Chin. Chem. Lett. 19 (2008) 423–427. [7] B. Reichart, C.O. Kappe, High-temperature continuous flow synthesis of 1,3,4oxadiazoles via N-acylation of 5-substituted tetrazoles, Tetrahedron Lett. 53 (2012) 952–955. [8] S. Guin, T. Ghosh, S.K. Rout, A. Banerjee, B.K. Patel, Cu(II) catalyzed imine C–H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles, Org. Lett. 13 (2011) 5976–5979. [9] C.O. Kangani, D.E. Kelley, B.W. Day, One pot direct synthesis of oxazolines, benzoxazoles, and oxadiazoles from carboxylic acids using the deoxo-fluor reagent, Tetrahedron Lett. 47 (2006) 6497–6499. [10] M. Kidwai, D. Bhatnagar, N.K. Mishra, Polyethylene glycol (PEG) mediated green synthesis of 2,5-disubstituted 1,3,4-oxadiazoles catalyzed by ceric ammonium nitrate (CAN), Green Chem. Lett. Rev. 3 (2010) 55–59. [11] F. Bentiss, M. Lagrene´e, D. Barbry, Rapid synthesis of 2,5-disubstituted 1,3,4oxadiazoles under microwave irradiation, Syn. Commun. 31 (2001) 935–938. [12] S.H. Mashraqui, S.G. Ghadigaonkarm, R.S. Kenny, An expeditious and convenient one pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles, Syn. Commun. 33 (2003) 2541–2545. [13] L. Zhang, H. Chen, Z.G. Zha, Z.Y. Wang, Electrochemical tandem synthesis of oximes from alcohols using KNO3 as the nitrogen source, mediated by tin microspheres in aqueous medium, Chem. Commun. 48 (2012) 6574–6576. [14] L. Zhang, J.H. Su, S.J. Wang, et al., Direct electrochemical imidation of aliphatic amines via anodic oxidation, Chem. Commun. 47 (2011) 5488–5490. [15] L. Zhang, Z.G. Zha, Z.L. Zhang, Y.F. Li, Z.Y. Wang, An electrochemical tandem reaction: one-pot synthesis of homoallylic alcohols from alcohols in aqueous media, Chem. Commun. 46 (2010) 7196–7198. [16] K. Rajeshwar, J.G. Ibanez, Environmental Electrochemistry – Fundamentals and Applications in Pollution Abatement, Academic Press, San Diego, 1997. [17] H. Lund, O. Hammerich, Organic Electrochemistry, 4th ed., Marcel Dekker, New York, 2001. [18] J. Grimshaw, Electrochemical Reactions and Mechanisms in Organic Chemistry, Elsevier, Amsterdam, 2000. [19] A.J. Bard, L.R. Faulkner, Electrochemical Methods: Fundamentals and Applications, Wiley-VCH, USA, 2003. [20] X.Q. Li, X.S. Xu, C. Zhou, Tetrabutylammonium iodide catalyzed allylic sulfonylation of a-methyl styrene derivatives with sulfonylhydrazides, Chem. Commun. 48 (2012) 12240–12250.