About this Journal Submit a Manuscript Table of Contents
ISRN Organic Chemistry
Volume 2012 (2012), Article ID 963195, 6 pages
http://dx.doi.org/10.5402/2012/963195
Research Article

A Convenient, TiCl4/SnCl4-Mediated Synthesis of N-Phenyl or N-Aryl Benzamidines and N-Phenylpicolinamidines

School of Chemical Sciences, North Maharashtra University, Jalgaon 425 001, India

Received 24 April 2012; Accepted 19 June 2012

Academic Editors: J. Mlochowski, D. Sémeril, and B. Zacharie

Copyright © 2012 Umesh D. Patil and Pramod P. Mahulikar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A new, TiCl4-or SnCl4-mediated, solvent-free method was developed for the synthesis of N-Aryl benzamidines and N-phenylpicolinamidines, in moderate-to-good yield, using suitable amines and nitriles as starting materials.

1. Introduction

The amidine nucleus is found in a wide variety of biologically active molecules [1]. N-Aryl amidine exhibits activity against Mycobacterium tuberculosis, and N-alkylfuramidine shows antiprotozoan and antimicrobial activities [2]. Similarly various amidines derived from 4-amidino-2-(2-pyridyl)quinazoline [3] and 1-amino-3-(2-pyridyl)isoquinoline [3], guanidine [4], diguanidino [5], reversed diamidino 2,5-diarylfuran [5], benzimidazole [6], pyridine [7], exhibit antimycoplasmal, antimalarial, antimicrobial, antibacterial, anti-inflammatory activities. An extensive number of monoamidines have been evaluated for their utility in blocking various stages of the thrombin cascade, and numerous highly potent molecules have been reported [8].

Amidines were used as important synthon in organic synthesis in the preparation of various heterocyclic compounds, such as pyridine [7, 9], pyrimidines [9, 10], imidazoles [11], pyrazolopyrimidine [12], iminopyrimidine [13], imidazopyridine and pyrimidinopyridine [14], purine [15], benzimidazole [16], pyrimidines [17], triazaphenalene [18], triazine [19], tetraazole [19], thiadiazine [20], oxazolotriazole [21], diazirine [22], triazolopyridine [23], azetidinone [24], and pyrrole, and also used as complexing agent [25].

Several synthetic strategies have been developed for the synthesis of amidines, in which the nucleophilic addition of amine to nitrile is the most popular. Generally, nitriles were activated to the intermediate salt in the presence of EtOH/HCl [26] or NH4Cl/MeOH [27] under anhydrous condition and then reacted with amine to get amidine. While for unreactive nitriles, Lewis acid or other condensing agents were used such as anhydrous AlCl3, ZnCl2 [28], CuCl [29], Ln (III) salts [30], CaCl2 [31], Al(CH3)3 [32], SmI2 [33], Ytterbium amide [34], MeSO3H [20], and anhyd. SnCl4 [21]. Amides can be converted to imidoyl chloride using PCl5 [35, 36], which can then react with primary or secondary amine to yield amidine. In addition, amide can be O-alkylated with triethyloxonium fluoroborate at ambient temperature to yield the corresponding imidic ester fluoroborate, which then reacts with amine to yield the targeted amidine [3]. Iron pentacarbonyl was employed to the conversion of amidoximes into amidines via reductive cleavage of the N=O bond [37]. Sometimes, strong bases like LiHMDS, NaHMDS, LDA, BuLi, NaOMe [38], and NaH [20] were used as condensing agent. Similarly, Dains F. B. has shown that amidine was prepared from symmetrical diaryl and dialkyl urea and acid chloride [39, 40].

In 1998, Zhou and Zhang published the results on such a subject that amidines were successfully prepared from nitriles and nitrocompounds in the presence of TiCl4/Sm in THF. They also reported that under same reaction conditions amidine formation was not observed by treatment of nitriles with amines [41]. Thus, it was of interest to study the reactions of nitrile and amine using TiCl4 and SnCl4.

2. Results and Discussion

We would like to demonstrate in the present work that amidine could be prepared by coupling nitrile with amine in presence of TiCl4 as well as SnCl4 using neat condition in absence of samarium. At the beginning we studied the synthesis of amidine (Scheme 1, Table 1, and Entry 1) using benzonitrile and aniline as model substrates. In a typical experiment aniline (0.01 mol) and benzonitrile (0.01 mol) were heated at 100–110°C with TiCl4 or SnCl4 (0.012 mol) for 3-4 hr to complete the reaction. The obtained black reaction mixture was then neutralised with NaOH solution and extracted with dichloromethane. Product was isolated simply by evaporation of the solvent at reduced pressure. The crude product was recrystallized from hexane. The obtained product was characterised by IR, NMR, and mass spectroscopy data and compared with authentic sample. Furthermore, the reaction was carried out for several substituted aryl amines and nitriles (Table 1) under the same conditions. It is distinct that both TiCl4 and SnCl4 were found to have a potential utility for the synthesis of amidine with good-to-moderate yields under mentioned reaction conditions.

tab1
Table 1: SnCl4/TiCl4 catalysed coupling of substituted anilines with benzonitrile.
963195.sch.001
Scheme 1

The mechanism we propose for the reaction is similar to the one reported for amidine using AlCl3 [42] and is outlined in Scheme 2: at first the complex between nitrile and TiCl4 was formed followed by nucleophilic addition of amine (2) on the more electrophilic carbon of nitriles to yield the amidine (3).

963195.sch.002
Scheme 2: Mechanism.

With these results in hand, we tested the scope and limitations of this process; we examined the coupling reaction of various substituted benzonitriles with heteroaromatic amine, that is, 2-aminopyridine, (Scheme 3 and Table 2) by performing the reaction with the well-established reaction conditions.

tab2
Table 2: SnCl4/TiCl4 catalysed coupling of 2-aminopyridine with substituted benzonitriles.
963195.sch.003
Scheme 3

Similarly, to test the scope and limitations of this process; we examined the coupling reaction of various substituted anilines with heteroaromatic nitrile, that is, 2-cyanopyridine, (Scheme 4 and Table 3) by performing the reaction with the well-established reaction conditions.

tab3
Table 3: SnCl4/TiCl4 catalysed coupling of substituted anilines with 2-cyanopyridine.
963195.sch.004
Scheme 4

3. Conclusion

In the summary, we have developed a solvent-free method of amidine formation from nitrile and amine using TiCl4 or SnCl4 in absence of expensive metal-like samarium. The reaction proceeded at 100–110°C and was completed within 3-4 hrs. In conclusion the reaction was extremely simple to carry out, and the obtained yield of amidine was good to moderate. On the basis of yield, we may conclude that TiCl4 is preferable catalyst over SnCl4.

4. Experimental

Melting points were determined by open capillary tube method and are uncorrected. Progress of the reaction was monitored by TLC (visualization was effected by exposure to UV light). Commercial reagents were used without purification for synthesis. Mass spectra were recorded on Thermo Finnigan (model- LCQ Advantage MAX) mass spectrometer. The IR spectra were recorded with KBr pellets on Perkin-Elmer Spectrum One Spectrometer. 1H NMR spectra were recorded in CDCl3 on a Bruker 300 DRX Avance instrument at 300 MHz.

4.1. Preparation of Amidines, 3a–o

Benzonitrile (1.03 g, 0.01 mol) was taken in a dry round bottom flask and to this was added a 2-aminopyridine (0.94 g, 0.01 mol). The flask was heated, after fitting a dry condenser along with a guard tube, in an oil bath at a temperature range of 80–90°C with stirring. After 30 min TiCl4 (1.3 mL, 0.012 mol) or SnCl4 (1.4 mL, 0.012 mol) was added to the flask. After addition, temperature was increased to 100–110°C, and contents of the flask were heated for 3-4 hrs. The mixture was cooled to room temperature, and the solid, thus, formed was dissolved in hot water and made alkaline with 10% NaOH. This solution was extracted with a CH2Cl2   ( 3 × 1 0 0 m L ) . Then organic layer was decolourized with activated charcoal and dried over anhydrous Na2SO4. After evaporating the solvent under reduced pressure, crude amidine was obtained. This crude product was recrystallized from hexane to get pure amidine.

N-Phenylbenzamidine (3a, C13H12N2)
1H NMR (CDCl3, δ ppm): 4.84 (br s, 2H, NH, C=NH), 6.96–6.99 (d, J=8.1 Hz, 2H, ArH), 7.03–7.08 (t, J=7.5 Hz 1H, ArH), 7.32–7.37 (t, J=7.8 Hz, 2H, ArH), 7.42–7.49 (m, 3H, ArH), 7.85 (s, 2H, ArH); IR (KBr) ν (cm−1): 3340, 2853, 1618, 1574, 1459, 1377, 1153, 722; MS (ESI, 70 eV) m/z (%): 198 (13), 197 (100) [M + H]+.

N-(2-Chlorophenyl)benzamidine (3b, C13H11ClN2)
1H NMR (CDCl3, δ ppm): 4.78 (br s, 2H, NH, C=NH), 6.97–7.02 (m, 2H, ArH), 7.19–7.22 (t, J=7.2 Hz,1H, ArH), 7.39–7.51 (m, 4H, ArH), 7.86 (br s, 2H, ArH); IR (KBr) ν (cm−1): 3345, 2853, 1618, 1574, 1459, 1377, 1153, 722; MS (ESI, 70 eV) m/z (%): 233 (37), 231(100) [M + H]+.

N-(4-Fluorophenyl)benzamidine (3c, C13H11FN2)
1H NMR (CDCl3, δ ppm): 4.86 (br s, 2H, 2NH), 6.90–6.94 (m, 2H, ArH), 7.01–7.07 (t, J=8.3 Hz, 2H, ArH), 7.41–7.46 (t, J=7.3 Hz, 3H, ArH), 7.83–7.86 (d, J=6.3 Hz, 2H, ArH); IR (KBr) ν (cm−1): 3348, 2854, 1625, 1590, 1459, 1377, 1152, 777, 722; MS (ESI, 70 eV) m/z (%): 216 (17), 215 (100) [M + H]+, 198 (13).

N-(Pyridin-2-yl)benzamidine (3d, C12H11N3)
1H NMR (CDCl3, δ ppm): 2.03 (bs, 2H, 2NH), 6.90–6.95 (m, 1H, ArH), 7.25–7.29 (d, J=9 Hz, 1H, ArH), 7.40–7.48 (m, 3H, ArH), 7.61–7.67 (m, 1H, ArH), 7.89–7.92 (m, 2H, ArH), 8.31–8.34 (m, 1H, ArH); IR (KBr) ν (cm−1): 3351, 2854, 1625, 1590, 1459, 1377, 1152, 777, 722; MS (ESI, 70 eV) m/z (%): 198 (100) [M + H]+.

3-Chloro-N-(pyridin-2-yl)benzamidine (3e, C12H10ClN3)
1H NMR (CDCl3, δ ppm): 2.03 (bs, 2H, 2NH), 6.92–6.96 (m, 1H, ArH), 7.25–7.45 (m, 3H, ArH), 7.62–7.68 (m, 1H, ArH), 7.72–7.73 (d, J=1.5 Hz, 1H, ArH), 7.92–7.93 (t, J=1.8 Hz, 1H, ArH), 8.32–8.34 (m, 1H, ArH); IR (KBr) ν (cm−1): 3341, 2854, 1625, 1590, 1459, 1377, 1152, 777, 722; MS (ESI, 70 eV) m/z (%): 231 (100) [M + H]+.

4-Chloro-N-(pyridin-2-yl)benzamidine (3f, C12H10ClN3)
1H NMR (CDCl3, δ ppm): 1.81 (br s, 2H, 2NH), 6.93–6.97 (m, 1H, ArH), 7.25–7.27 (t, J=8.1 Hz,1H, ArH), 7.41–7.43 (d, J=6.3 Hz, 2H, ArH), 7.63–7.69 (m, 1H, ArH), 7.85–7.89 (d, J=6.9 Hz, 2H, ArH), 8.33–8.35 (m, 1H, ArH); IR (KBr) ν (cm−1): 3344, 2853, 1618, 1594, 1462, 1377, 1125, 831, 782, 722, 538; MS (ESI, 70 eV) m/z (%): 231 (100) [M + H]+.

4-Bromo-N-(pyridin-2-yl)benzamidine (3g, C12H10BrN3)
1H NMR (CDCl3, δ ppm): 1.78 (br s, 2H, 2NH, C=NH), 6.92–6.97 (m, 1H, ArH), 7.24–7.27 (t, J=3.9 Hz,1H, ArH), 7.55–7.60 (m, 2H, ArH), 7.63–7.69 (m, 1H, ArH), 7.72–7.81 (m, 2H, ArH), 8.32–8.35 (m, 1H, ArH); IR (KBr) ν (cm−1): 3349, 2854, 1640, 1577, 1530, 1459, 1377, 1321, 1300, 1260, 1151, 1119, 1096, 1006, 818, 769, 722, 541; MS (ESI, 70 eV) m/z (%): 278 (100), 276 (100) [M + H]+.

N-(5-Bromopyridin-2-yl)benzamidine (3h, C12H10BrN3)
1H NMR (CDCl3, δ ppm): 1.68 (br s, 2H, NH), 7.16–7.19 (d, 1H, ArH), 7.42–7.49 (m, 3H, ArH), 7.71–7.75 (m, 1H, ArH), 7.88–7.91 (t, J=6 Hz, 2H, ArH), 8.37–8.38 (d, J=2.4 Hz, 1H, ArH); IR (KBr) ν (cm−1): 3350, 2853, 1618, 1574, 1459, 1377, 1153, 722; MS (ESI, 70 eV) m/z (%): 278 (94), 276 (100) [M + H]+, 260 (90), 259 (90).

N-Phenylpicolinamidine (3i, C12H11N3)
1H NMR (CDCl3, δ ppm): 5.91 (br s, 2H, NH, C=NH), 6.88–7.26 (m, 4H, ArH), 7.31–7.37 (m, 2H, ArH), 7.78–7.81 (m, 1H, ArH), 8.41–8.45 (m, 1H, ArH), 8.52–8.59 (m, 1H, ArH); IR (KBr) ν (cm−1): 3346, 2853, 1618, 1574, 1459, 1377, 1153, 722; MS (ESI, 70 eV) m/z (%): 198 (100) [M + H]+, 181 (45).

N-o-tolylpicolinamidine (3j, C13H13N3)
1H NMR (CDCl3, δ ppm): 2.18 (s, 3H, ArCH3), 5.72 (br s, 2H, NH, C=NH), 6.89–7.02 (m, 2H, ArH), 7.16–7.24 (q, J=7.8 Hz, 1H, ArH), 7.30–7.33 (dd, J=8.4 Hz,1H, ArH), 7.36–7.41 (m, 1H, ArH), 7.77–7.84 (m, 1H, ArH), 8.36–8.48 (m, 1H, ArH), 8.55–8.57 (m, 1H, ArH); IR (KBr) ν (cm−1): 3345, 1694, 1613, 1463, 1377, 1118, 721; MS (ESI, 70 eV) m/z (%): 212 (100) [M + H]+, 195 (37).

N-p-tolylpicolinamidine (3k, C13H13N3)
1H NMR (CDCl3, δ ppm): 2.18 (s, 3H, ArCH3), 5.58 (br s, 2H, NH, C=NH), 6.90–7.01 (m, 3H, ArH), 7.18–7.26 (m, 2H, ArH), 7.36–7.40 (m, 1H, ArH), 7.56 (m, 1H, ArH), 7.77–7.84 (m, 1H, ArH); IR (KBr) ν (cm−1): 3339, 2854, 1694, 1613, 1463, 1377, 1118, 721; MS (ESI, 70 eV) m/z (%): 212 (100) [M + H]+, 195 (37).

N-(4-Fluorophenyl)picolinamidine (3l, C12H10FN3)
1H NMR (CDCl3, δ ppm): 1.76 (br s, 1H, NH), 5.81 (br s, 1H, NH), 6.88–7.02 (m, 4H, ArH), 7.32–7.35 (m, 1H, ArH), 7.73–7.78 (m, 1H, ArH), 8.32–8.34 (d, J=6 Hz, 1H, ArH), 8.49–8.50 (d, J=6 Hz, 1H, ArH); IR (KBr) ν (cm−1): 3378, 2854, 1625, 1590, 1459,1377, 1152, 777, 722; MS (ESI, 70 eV) m/z (%): 216 (100) [M + H]+, 199 (25).

N-(4-Chlorophenyl)picolinamidine (3m, C12H10ClN3)
1H NMR (CDCl3, δ ppm): 5.86 (br s, 2H, NH, C=NH), 6.84–6.88 (m, 2H, ArH), 7.25–7.42 (m, 3H, ArH), 7.73–7.82 (t, J=5.7 Hz, 1H, ArH), 8.29–8.40 (m, 1H, ArH), 8.51–8.59 (m, 1H, ArH); IR (KBr) ν (cm−1): 3345, 2853, 1618, 1574, 1459, 1377, 1153, 722; MS (ESI, 70 eV) m/z (%): 232 (100) [M + H]+, 215 (33).

N-(4-Bromophenyl)picolinamidine (3n, C12H10BrN3)
1H NMR (CDCl3, δ ppm): 5.85 (br s, 2H, NH, C=NH), 6.88–6.91 (d, J=8.7 Hz, 2H, ArH), 7.38–7.50 (m, 3H, ArH), 7.79–7.84 (m, 1H, ArH), 8.36–8.39 (d, J=8.1 Hz, 1H, ArH), 8.56–8.58 (m, 1H, ArH); IR (KBr) ν (cm−1): 3376, 2854, 1640, 1577, 1530, 1459, 1377, 1321, 1300, 1260, 1151, 1119, 1096, 1006, 818, 769, 722, 541; MS (ESI, 70 eV) m/z (%): 278 (100), 276 (100) [M + H]+, 260 (20), 259 (20).

N-(3,4-Dichlorophenyl)picolinamidine (3o, C12H9Cl2N3)
1H NMR (CDCl3, δ ppm): 5.97 (br s, 2H, 2NH), 6.84–6.88 (m, 1H, ArH), 7.12–7.17 (t, 1H, ArH), 7.39–7.43 (t, J=3.9 Hz,2H, ArH), 7.79–7.87 (t, J=9.6 Hz, 1H, ArH), 8.33–8.36 (d, J=7.8 Hz,1H, ArH), 8.56–8.58 (d, J=4.5 Hz, 1H, ArH); IR (KBr) ν (cm−1): 3345, 1694, 1613, 1463, 1377, 1118, 721; MS (ESI, 70 eV) m/z (%): 267 (100), 266(65) [M + H]+.

References

  1. S. Patai and Z. Rappoport, The Chemistry of Amidines and Imidates, vol. 27, John Wiley & Sons, New York, NY, USA, 1991.
  2. S. M. Rahmathullah, R. R. Tidwell, S. K. Jones, J. E. Hall, and D. W. Boykin, “Carbamate prodrugs of N-alkylfuramidines,” European Journal of Medicinal Chemistry, vol. 43, no. 1, pp. 174–177, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. M. A. H. de Zwart, H. van der Goot, and H. Timmerman, “Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2-pyridyl)isoquinoline derivatives. 2. Amidines,” Journal of Medicinal Chemistry, vol. 32, no. 2, pp. 487–493, 1989. View at Scopus
  4. M. Calas, M. Ouattara, G. Piquet et al., “Potent antimalarial activity of 2-aminopyridinium salts, amidines, and guanidines,” Journal of Medicinal Chemistry, vol. 50, no. 25, pp. 6307–6315, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. C. E. Stephens, F. Tanious, S. Kim et al., “Diguanidino and “reversed” diamidino 2,5-diarylfurans as antimicrobial agents,” Journal of Medicinal Chemistry, vol. 44, no. 11, pp. 1741–1748, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Göker, S. Özden, S. Yildiz, and D. W. Boykin, “Synthesis and potent antibacterial activity against MRSA of some novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidines,” European Journal of Medicinal Chemistry, vol. 40, no. 10, pp. 1062–1069, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. S. V. Bhosale, U. D. Patil, M. B. Kalyankar, S. V. Nalage, V. S. Patil, and K. R. Desale, “Facile synthesis of 2,6-diaryl-4-secondary aminonicotinonitriles and highly substituted unsymmetrical 2,2′-bipyridines,” Journal of Heterocyclic Chemistry, vol. 47, no. 3, pp. 691–696, 2010. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Frédérick, L. Pochet, C. Charlier, and B. Masereel, “Modulators of the coagulation cascade: focus and recent advances in inhibitors of tissue factor, factor VIIa and their complex,” Current Medicinal Chemistry, vol. 12, no. 4, pp. 397–417, 2005. View at Scopus
  9. R. Pratap, B. Kumar, and V. J. Ram, “An efficient substituent dependent synthesis of congested pyridines and pyrimidines,” Tetrahedron, vol. 63, no. 41, pp. 10309–10319, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. N. Agarwal, P. Srivastava, S. K. Raghuwanshi et al., “Chloropyrimidines as a new class of antimicrobial agents,” Bioorganic and Medicinal Chemistry, vol. 10, no. 4, pp. 869–874, 2002. View at Publisher · View at Google Scholar · View at Scopus
  11. J. F. Cheng, M. Chen, B. Liu, Z. Hou, T. Arrhenius, and A. M. Nadzan, “Design and synthesis of heterocyclic malonyl-CoA decarboxylase inhibitors,” Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 3, pp. 695–700, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. N. D. Adams, S. J. Schmidt, S. D. Knight, and D. Dhanak, “A novel synthesis of substituted 4H-pyrazolo[3,4-d]pyrimidin-4-ones,” Tetrahedron Letters, vol. 48, no. 23, pp. 3983–3986, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. McCauley, C. R. Theberge, and N. J. Liverton, “Chemoselective reactions of amidines: selective formation of iminopyrimidine regioisomers,” Organic Letters, vol. 2, no. 21, pp. 3389–3391, 2000. View at Scopus
  14. M. W. Cartwright, G. Sandford, J. Bousbaa et al., “Imidazopyridine and pyrimidinopyridine systems from perfluorinated pyridine derivatives,” Tetrahedron, vol. 63, no. 30, pp. 7027–7035, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. B. G. Szczepankiewicz, J. J. Rohde, and R. Kurukulasuriya, “Synthesis of purines and other fused imidazoles from acyclic amidines and guanidines,” Organic Letters, vol. 7, no. 9, pp. 1833–1835, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. V. J. Grenda, R. E. Jones, G. Gal, and M. Sletzinger, “Novel preparation of benzimidazoles from N-arylamidines. New synthesis of thiabendazole,” Journal of Organic Chemistry, vol. 30, no. 1, pp. 259–261, 1965. View at Scopus
  17. R. Pratap, Farahanullah, R. Raghunandan, P. R. Maulik, and V. J. Ram, “Substituent directed regioselective synthesis of 2-oxonicotonic acids and methyl nicotinates,” Tetrahedron Letters, vol. 48, no. 28, pp. 4939–4942, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Pratap, A. D. Roy, S. P. Kushwaha, A. Goel, R. Roy, and V. J. Ram, “Guanidine and amidine mediated synthesis of bridgehead triazaphenalenes, pyrimidines and pyridines through domino reactions,” Tetrahedron Letters, vol. 48, no. 33, pp. 5845–5849, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. J. J. Shie and J. M. Fang, “Microwave-assisted one-pot tandem reactions for direct conversion of primary alcohols and aldehydes to triazines and tetrazoles in aqueous media,” Journal of Organic Chemistry, vol. 72, no. 8, pp. 3141–3144, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Zienkiewicz, P. Kaszynski, and V. G. Young, “Fused-ring thiadiazines: preparation and crystallographic characterization of 3-phenyl derivative of benzo-, pyridio[2,3-e]-, pyrazino[2,3-e]-, and tetrafluorobenzo-[1,2,4]thiadiazines,” Journal of Organic Chemistry, vol. 69, no. 7, pp. 2551–2561, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Sambaiah and K. K. Reddy, “Synthesis of 2-Aryl[1,2,4]triazolo[5,1-b]benzoxazoles by oxidative cyclization of N-(benzoxazol-2-yl)benzamidines,” Synthesis, no. 5, pp. 422–424, 1990.
  22. W. H. Graham, “The halogenation of amidines. I. Synthesis of 3-halo- and other negatively substituted diazirines,” Journal of the American Chemical Society, vol. 87, no. 19, pp. 4396–4397, 1965. View at Scopus
  23. K. T. Potts, H. R. Burton, and J. Bhattacharyya, “1,2,4-Triazoles. XIII. Derivatives of the s-triazolo[1,5-a]pyridine ring system,” Journal of Organic Chemistry, vol. 31, no. 1, pp. 260–265, 1966. View at Scopus
  24. A. K. Bose and I. Kugajevsky, “Studies on lactams-VII. A new synthesis of β-amino-β-lactams,” Tetrahedron, vol. 23, no. 2, pp. 957–963, 1967. View at Scopus
  25. R. K. Mahajan and P. Dhawan, “Adsorptive stripping voltammetric determination of nickel(II) using N-2-pyridyl-benzamidine as a complexing reagent,” Indian Journal of Chemistry A, vol. 41, no. 5, pp. 981–984, 2002. View at Scopus
  26. R. Roger and D. G. Neilson, “The chemistry of imidates,” Chemical Reviews, vol. 61, no. 2, pp. 179–211, 1961. View at Scopus
  27. K. Dabak, “Synthesis and protection of some amidines,” Turkish Journal of Chemistry, vol. 26, no. 4, pp. 547–550, 2002. View at Scopus
  28. J. D. Bower and G. R. Ramage, “Heterocyclic systems related to pyrrocoline. Part II. The preparation of polyazaindenes by dehydrogenative cyclisations,” Journal of the Chemical Society (Resumed), pp. 4506–4510, 1957. View at Scopus
  29. G. Rousselet, P. Capdevielle, and M. Maumy, “Copper(I)-induced addition of amines to unactivated nitriles: the first general one-step synthesis of alkyl amidines,” Tetrahedron Letters, vol. 34, no. 40, pp. 6395–6398, 1993. View at Publisher · View at Google Scholar · View at Scopus
  30. J. H. Forsberg, V. T. Spaziano, T. M. Balasubramanian et al., “Use of lanthanide(III) ions as catalysts for the reactions of amines with nitriles,” Journal of Organic Chemistry, vol. 52, no. 6, pp. 1017–1021, 1987. View at Scopus
  31. M. Meder, C. H. Galka, and L. H. Gade, “Bis(2-pyridylimino)isoindole (BPI) ligands with novel linker units: synthesis and characterization of their palladium and platinum complexes,” Monatshefte fur Chemie, vol. 136, no. 10, pp. 1693–1706, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. B. Asproni, A. Pau, M. Bitti et al., “Synthesis and pharmacological evaluation of 1-[(1,2-diphenyl-1H-4-imidazolyl)methyl]-4-phenylpiperazines with clozapine-like mixed activities at dopamine D2, serotonin, and GABAA receptors,” Journal of Medicinal Chemistry, vol. 45, no. 21, pp. 4655–4668, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. F. Xu, J. Sun, and Q. Shen, “Samarium diiodide promoted synthesis of N,N′-disubstituted amidines,” Tetrahedron Letters, vol. 43, no. 10, pp. 1867–1869, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Wang, F. Xu, T. Cai, and Q. Shen, “Addition of amines to nitriles catalyzed by ytterbium amides: an efficient one-step synthesis of monosubstituted N-arylamidines,” Organic Letters, vol. 10, no. 3, pp. 445–448, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. M. W. Partridge and A. Smith, “Cyclic amidines. Part XXIV. Cyclisation of N-allyl-N′- arylacetamidines to imidazolines, dihydroquinazolines, and dihydrobenzodiazepines,” Journal of the Chemical Society, Perkin Transactions 1, pp. 453–456, 1973. View at Scopus
  36. A. J. Hill and J. V. Johnston, “Amidines derived from ethylenediamine. I. Diamidines,” Journal of the American Chemical Society, vol. 76, no. 3, pp. 920–922, 1954. View at Scopus
  37. A. Dondoni and G. Barbaro, “Synthetic reactions using transition metal complexes. Conversion of amide oximes into amidines by pentacarbonyliron and evidence for imine intermediates in the deoximation of ketoximes,” Journal of the Chemical Society, Chemical Communications, no. 18, pp. 761–762, 1975. View at Publisher · View at Google Scholar · View at Scopus
  38. I. K. Khanna, Y. Yu, R. M. Huff et al., “Selective cyclooxygenase-2 inhibitors: heteroaryl modified 1,2-diarylimidazoles are potent, orally active antiinflammatory agents,” Journal of Medicinal Chemistry, vol. 43, no. 16, pp. 3168–3185, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. F. B. Dains, “On the action of certain acid reagents on the substituted ureas,” Journal of the American Chemical Society, vol. 22, no. 4, pp. 181–198, 1900. View at Scopus
  40. F. B. Dains, R. C. Roberts, and R. Q. Brewster, “On the action of certain acid reagents on the substituted ureas and thiazole,” Journal of the American Chemical Society, vol. 38, no. 1, pp. 131–140, 1916. View at Scopus
  41. L. Zhou and Y. Zhang, “Low-valent titanium induced reductive coupling of nitriles with nitro compounds,” Synthetic Communications, vol. 28, no. 17, pp. 3249–3262, 1998. View at Scopus
  42. P. Oxley, M. W. Partridge, and W. F. Short, “Amidines. Part VII. Preparation of amidines from cyanides, aluminium chloride, and ammonia or amines,” Journal of the Chemical Society (Resumed), pp. 1110–1116, 1947. View at Scopus