Metal chloride hydrates as Lewis acid catalysts in multicomponent synthesis of 2,4,5-triarylimidazoles or 2,4,5-triaryloxazoles

SHORT REPORT

Metal chloride hydrates as Lewis acid catalysts in multicomponent synthesis of 2,4,5-triarylimidazoles or 2,4,5-triaryloxazoles

Marcelo V. Marques^{I, II}; Marcelo M. Ruthner^III; Luiz A. M. Fontoura^{I, III,}; Dennis Russowsky^II,*

^IDepartamento de Engenharia de Processos, Fundação de Ciência e Tecnologia, 94930-230 Cachoeirinha-RS, Brazil

^IILaboratório de Sínteses Orgânicas, Instituto de Química, Universidade Federal do Rio Grande do Sul, 91501-970 Porto Alegre-RS, Brazil

^IIICurso de Química, Universidade Luterana do Brasil, 92452-900 Canoas-RS, Brazil

ABSTRACT

A series of nine metal chloride hydrates (ZnCl₂.2H₂O, SnCl₂.2H₂O, CdCl₂.2H₂O, MnCl₂.4H₂O, CoCl₂.6H₂O, SrCl₂.6H₂O, NiCl₂.6H₂O, CrCl₃.6H₂O and CeCl₃.7H₂O) was investigated as mild and inexpensive Lewis acid catalysts to promote the multicomponent synthesis of triarylimidazoles. Reactions starting from benzil showed the best results when SnCl₂.2H₂O was used, while for benzoin as the starting material, CeCl₃.7H₂O was more efficient. All reactions were performed in EtOH as solvent. These catalysts were also successfully employed in the synthesis of triaryloxazoles.

Keywords: triarylimidazoles, triaryloxazoles, multicomponent reaction, metal halide hydrates, Lewis acids, Radziszewski reaction, benzil, benzoin

RESUMO

Uma série de nove hidratos de cloretos metálicos (ZnCl₂.2H₂O, SnCl₂.2H₂O, CdCl₂.2H₂O, MnCl₂.4H₂O, CoCl₂.6H₂O, SrCl₂.6H₂O, NiCl₂.6H₂O, CrCl₃.6H₂O e CeCl₃.7H₂O) foi investigada como catalisadores ácidos de Lewis brandos e baratos na síntese multicomponente de triarilimidazóis. O melhor catalisador para as reações com benzila foi o SnCl₂.2H₂O, enquanto que para as reações com benzoína, o CeCl₃.7H₂O foi mais eficiente. Todas as reações foram efetuadas em EtOH como solvente. Estes catalisadores também foram empregados igualmente com sucesso na síntese de triariloxazóis.

Introduction

Imidazole is a five-membered ring heteroaromatic compound with two nitrogen atoms at 1 and 3 positions.¹ This type of compound is known to exhibit a broad range of pharmaceutical and industrial applications. For instance, the imidazole core unity is present in many compounds with pronounced biologic activities such as angiotensin inhibitors,² anti-inflammatory,³ glucagon antagonist,⁴ antiviral,⁵ antimicrobial,⁶ fungicidal⁷ and high cytotoxicity, which has indicated them as new candidates in cancer therapy.⁸

A particular class of triarylimidazoles, the pyridinyl arylimidazoles 1, 2 and 3 have been recognized as a potent p38 mitogen-activated protein (MAP) kinase inhibitors and emerged as possible therapeutic drugs in the treatment of various diseases such as cancer and as anti-inflammatory agent, combating the associated pain with osteoarthritis (Figure 1).⁹ Beyond the pharmacological applications, arylimidazoles have been used in the industry as chemiluminescent¹⁰ and chromotropic materials¹¹ due to their optic and electronic properties.¹²

The synthesis of triarylimidazoles from the three-component reaction of 1,2-dicarbonyl compounds, aldehyde and ammonia was independently discovered by Japp and Robinson¹³ in 1882 and Radziszewski.¹⁴ However, long periods of time and harsh conditions were frequently associated with low yields of production. Davidson et al.¹⁵ showed to be possible to reduce the reaction times using acetic acid as solvent and ammonium acetate instead of ammonia. This last protocol became usual and default procedure for the synthesis of triarylimidazoles.

Recently, Kamijo and Yamamoto¹⁶ have reviewed the progress on the synthesis of imidazoles through catalyzed process. Besides other methods using Brønsted catalysis of p-toluenesulfonic acid (p-TSA),¹⁷ heteropolyacids,¹⁸ oxalic acid¹⁹ and phosphomolybdic acid²⁰ were developed. Heterogeneous catalysts based on silica-supported Brønsted or Lewis acids, such as HClO₄/SiO₂,²¹ H₂SO₄/SiO₂,²² BF₃/SiO₂,²³ NaHSO₄/SiO₂²⁴ or zeolites HY-type,²⁵ were successfully employed. Microwave,²⁶ ultrasound irradiation²⁷ and ionic liquids²⁸ were also reported as efficient promoters to the synthesis of arylimidazoles. Other solid catalysts, such as NaHSO₃²⁹ or I₂³⁰ and proline³¹ or tetrabutylammonium bromide (TBAB)³² as organocatalysts, were also effective. Although many catalysts have been employed in the Radziszewski reaction, the use of Lewis acid catalysts such as metal triflates as Yb(OTf)₃,³³ metal halides as ZrCl₄,³⁴ Zn(acac)₄²⁷ or cerium ammonium nitrate³⁵ are rare. Additionally, few examples of metal halide hydrates like InCl₃.3H₂O³⁶ and NiCl₂.6H₂O/Al₂O₃³⁷ were reported for the synthesis of these compounds.

The previous experience of our research group on the use of highly moisture sensitive metal halides as Lewis acid catalysts in organic reactions³⁸ prompt us to investigate the similar ability of the metal halide hydrates, which are cheaper, easily handled and compatible moisture. Fortunately, our group discovered that SnCl₂.2H₂O was successfully employed in the Biginelli reaction,³⁹ Friedlander condensation⁴⁰ and in conjugate Friedel-Crafts reaction.⁴¹ In the present work, we explore the ability of a series of metal chloride hydrates (SnCl₂.2H₂O, ZnCl₂.2H₂O, CdCl₂.2H₂O, MnCl₂.4H₂O, CoCl₂.6H₂O, SrCl₂.6H₂O, NiCl₂.6H₂O, CrCl₃.6H₂O and CeCl₃.7H₂O) as mild and inexpensive Lewis acid catalysts in the multicomponent Radziszewski reaction. Besides the search for catalyst efficiency, variables such as protic/aprotic solvents and molar ratio of reagents and catalyst were investigated towards the optimization of a general and useful protocol.

Results and Discussion

Catalysts

To investigate the abilities of metal chloride hydrates as Lewis acid catalysts, lophine (2,4,5-triphenyl-1H-imidazole) (8a) was chosen as the model compound. In a first example, the reaction of benzil (4a, 1.0 mmol), benzaldehyde (6a, 1.0 mmol ), NH₄OAc (7, 4.0 mmol) and SnCl₂.2H₂O (0.10 mmol) was carried out in gently refluxing EtOH. The course of the reaction was monitored by thin layer chromatography (TLC) and after a period of 4 h, the starting materials were consumed. After this time, the reaction was stopped and the crude product was isolated (Table 1, entry 2). Therefore, this time was chosen as default for comparison with other catalysts (Scheme 1).

The same conditions were applied for the reactions with benzoin (5, 1.0 mmol) instead of benzil, and the results are shown in the Table 1. In all cases, the metal chloride hydrates showed catalytic activity affording lophine in variable yield. It should be noted that in the absence of the catalyst, the yield was drastically reduced, evidencing the metal halide activity (see Table 1, entry 1). The best results (higher than 80% yield) starting from benzil (4) were found in the presence of SnCl₂.2H₂O and MnCl₂.2H₂O (entries 2 and 3, respectively). On the other hand, the optimum result with benzoin (5) was achieved in the presence of CeCl₃.7H₂O (entry 10). The decrease in the catalyst amount from 0.10 to 0.05 mmol afforded worse results for both starting ketones (entries 11 and 12). Finally, the reactions that were carried out for 2 h caused a decrease in the yield of the product, while an increase of 6 h in the time of the reaction led only to a small improvement (cf. entries 10 and 14, respectively). Therefore, it was decided to explore the use of SnCl₂.2H₂O and CeCl₃.7H₂O (0.10 mmol) as the main catalysts and the time of 4 h as default.

Different mechanistic pathways have been proposed for this multicomponent reaction having the benzil or benzoin as starting materials.^15,28,33 The proposed rationale by Kokare et al.¹⁹ seems to be in accordance with the results in Table 1 (Scheme 2). The authors suggested the initial formation of N,N-ketal (9) under Brønsted acidic catalysis from benzaldehyde (6a) and 2 equivalents of NH₄OAc (7). It was assumed that the same activation occurs in the Lewis catalysis. Therefore, the condensation of 9 with benzil (4a) after losing 2 equivalents of water, leads to the conjugate intermediate 10 which rearranges via a [1,5]-sigmatropic proton shift to afford the corresponding lophine (8a).

On the other hand, starting from benzoin, the cyclization of intermediate imino-alcohol (11) should occur by an intramolecular attack of nitrogen in a more hindered and saturated carbon to afford the dihydroimidazole intermediate (12) (Scheme 3). Additionally, the needed oxidation step to produce the conjugated intermediate (10) could be corroborating to explain the minor reactivity that is observed in reactions starting from benzoin. The intermediate (10) is suggested as common specie in both mechanistic pathways.

Solvent

Despite the use of H₂O,⁴² MeOH, EtOH, i-PrOH, CH₂Cl₂, THF, 1,4-dioxane⁴³ or CH₃CN³⁴ as solvents has already been reported in presence of different catalysts, the relative influence of alcoholic solvents in the Radziszewski reaction was not well studied. For this purpose, were investigated the reactions of benzil (4a, 1 mmol) or benzoin (5, 1 mmol), benzaldehyde (6a, 1.0 mmol), NH₄OAc (7, 4.0 mmol) and the catalyst (0.10 mmol) carried out in MeOH, EtOH, n-PrOH, CH₃CN and THF (tetrahydrofuran) promoted by SnCl₂.2H₂O or CeCl₃.7H₂O for the synthesis of lophine (8a, Scheme 4). The results are shown in the Table 2, bellow.

Table 2 shows the solvents, their dipole moments (µ) and relative dielectric constants (ε).⁴⁴ The reaction from benzyl in the presence of SnCl₂.2H₂O seems to be more influenced by the solvent (Table 2, entries 1-5). Aprotic solvents led to poorer yields. In the case of CH₃CN (the most polar between them), the solvent might be associating to the catalyst in a stronger way than the other ones do, reducing more significantly the reaction rate (entry 4). On the other hand, from benzoin and CeCl₃.7H₂O, the yields are essentially the same for all the solvents, protic or aprotic (entries 6-10). The effect of CH₃CN is not observed, which might be attributed to the metal volume, making their association more difficult (entry 9). Besides the effects of polarity of the solvents, their ability in acting as "hydrogen bond donors" can be considered. This new principle can be evidenced in the activation process through the hydrogen bonding between the solvent and reactants on organocatalyzed reactions, as recently reviewed by Akiyama.⁴⁵ Therefore, based on the results above discussed and on economical and ambient sustainability reasons, lower toxicity and easy availability, ethanol becomes more advantageous solvent and was chosen as a default solvent in our present study.

Molar ratio of NH₄OAc

Next, it was investigated the influence of the molar ratio of NH₄OAc on the synthesis of lophine under catalysis of SnCl₂.2H₂O and CeCl₃.7H₂O. The molar ratio of benzil (4a, 1.0 mmol) or benzoin (5, 1.0 mmol), benzaldehyde (6a, 1.0 mmol) and catalyst (0.10 mmol) were the same for all performed assays. The results are shown in Table 3. From substrates, 4a or 5, the increase in the NH₄OAc amount from 2 to 4 mmol was followed by an improvement on the reaction yield (cf. entries 1, 2 and 4, 5, respectively).

From substrates, benzyl or benzoin, the increase in the NH₄OAc amount from 2 to 4 mmol was followed of an improvement on the reaction yield (cf. entries 1, 2 and 4, 5, respectively). Using 10 mmol of NH₄OAc, a little improvement from benzyl was observed (entry 3). In contrast, a poorer yield from benzoin (entry 6) was achieved. In summary, 4 mmol (2 molar equivalents) were considered the optimum amount of this reagent. This developed protocol was applied to the reaction of benzils (4a-c) and benzoin (5) with aldehydes (6a-k) to afford a library of triarylimidazoles (8a-p) (Scheme 5). The results are show in the Table 4.

Pyrazine and triaryloxazoles

The decrease in the yield when 10 mmol of NH₄OAc was employed with benzoin (5, see Table 3, entry 6) was attributed to the formation of pyrazine (13) as a byproduct (identified by GC-MS analysis).

Similar observation was already reported in the literature.¹⁵ Intending to confirm this hypothesis, it was performed the reaction of benzoin (5, 2.0 mmol), NH₄OAc (7, 4.0 mmol) under refluxing of ethanol and CeCl₃.7H₂O (0.10 mmol) over 4 h in absence of the aldehyde. After this time, the pyrazine (13) was isolated in 87% yield (Scheme 6).

On the other hand, the reaction of benzil (4a, 2.0 mmol) with ammonium acetate (7, 4.0 mmol) under refluxing of ethanol and SnCl₂.2H₂O (0.10 mmol) over 4 h afforded the triaryloxazole (10a) in 74% yield (Scheme 7).

Davidson et al.¹⁵ early reported the formation of 2,4,5-trifenyloxazole as a lateral product in the Radziszewski reaction under acetic acid media. By the proposed mechanistic pathway suggested by Davidson et al.,¹⁵ it is clear the aid of acetic acid as a Brønsted acid catalyst. Triaryloxazoles are structurally similar to triarylimidazoles and also have some of their properties, but have been less studied so far. Due to their broad application (for example, in nonlinear optical devices⁴⁶ or as biologically active compounds),⁴⁷ it was decided to investigate the ability of metal chloride hydrates such as NiCl₂.6H₂O, ZnCl₂.2H₂O, MnCl₂.4H₂O and SnCl₂.2H₂O to participate as Lewis acid catalysts in the synthesis of triaryloxazoles. The results are shown in Table 5.

The reactions were carried out as described in the synthesis of lophine (see Table 1). In the absence of the catalyst (Table 5, entry 1), 10a was only isolated in a poor yield. The same result was observed when NiCl₂.6H₂O or MnCl₂.4H₂O was added (entries 2 and 3). Changing the catalyst to ZnCl₂.2H₂O, an increase in the yield was observed. In the presence of SnCl₂.2H₂O, a reasonable yield (78%) was achieved (entries 4 and 5, respectively). Other solvents were also investigated. The reactions were carried out under reflux. In MeOH, a decrease in the yield was observed, while the use of n-PrOH permitted to isolate the product in a yield of 73% (entries 6 and 7, respectively). On the other hand, in CH₃CN and THF (aprotic polar solvents), benzyl was recovered after the work up (entries 8 and 9, respectively). So, EtOH was considered to be the best solvent. After that, the amount of catalyst was diminished from 10 to 5 mol% (cf. entries 5 and 10, respectively) and no significant decrease in the yield was observed, therefore, this new condition was set as default.

Finally, the increase in the reaction times also caused an increase in the yield of triaryloxazole (14a), 84 and 94% (entries 11 and 12, respectively). The use of benzyl (4c) under the optimized protocol afforded the triaryloxazole (14b) in good yield, confirming the applicability of this protocol.

Conclusions

We found that the metal halide hydrates were active as Lewis acid catalyst to prepare 2,4,5-triarylimidazoles in reasonable to good yields through the Radziszewski multicomponent synthesis. These catalysts were effective starting from benzoin, as well as from benzils. The SnCl₂.2H₂O showed the best results in reactions from benzyl, while CeCl₃.7H₂O was more effective with benzoin. Additionally, we demonstrate that the molar ratio of NH₄OAc is important to improve the yields of the products and the large excess of them can leads to the formation of 1,2,4,5-tetraarylpyrazines. The SnCl₂.4H₂O was also effective to promote the reaction of benzils with NH₄OAc to afford the respective triaryloxazoles in good yields.

Experimental

General considerations

The solvents and reagents were used without previous treatment, except for benzaldehyde, anisaldehyde and furfural, which were distilled prior to use. The reactions were monitored by thin layer chromatography (TLC) on ALUGRAM^® SIL G/UV 254 Macherey-Nagel silicagel plates. A mixture CH₂Cl₂/AcOEt in 98:2 ratios was used as eluent. The plates were visualized in alcoholic solution of 2,4-dinitrofenilidrazine or under UV light (254 nm). The ¹H and ¹³C nuclear magnetic resonance (NMR) spectra were recorded in DMSO-d₆ using a Varian VNMRS or a Varian Mercury spectrometers at 300/400 MHz and 75/100 MHz, respectively. The chemical shifts (δ) are reported in parts per million (ppm) relative to DMSO-d₆ at δ 2.50 ppm for ¹H NMR and the line at δ 39.5 ppm for ¹³C NMR. The coupling constants J are reported in Hz. The following abbreviations are used for the multiplicities: s (singlet), d (doublet), dd (double of doublets), t (triplet), q (quartet), m (multiplet) and br s (broad singlet). The infrared (IR) spectra were recorded on a Perkin-Elmer Spectrum One, between 4000 and 600 cm^-1 (Nujol). The melting points (mp) were measured on an Uniscience Brazil fusing equipment (model 498) and are uncorrected. The mass spectra (MS) were recorded on a GC-MS QP 2010 Shimadzu (EI, 70 eV).

General procedures

Synthesis of 2,4,5-triarylimidazoles (8a-p) from benzyls (4a-c)

A 10 mL round-bottom flask equipped with magnetic stirrer was charged with benzyls (4a-c) (1.0 mmol), aldehydes (6a-k) (1.0 mmol), NH₄OAc (7, 4.0 mmol) and SnCl₂.2H₂O (0.10 mmol), followed by EtOH (4 mL). The reaction mixture was stirred and gently refluxed for 4 h. After the completion of the reaction with the monitoring of TLC, 4 mL of water were added. The solid was filtered under reduced pressure and washed with small portions of a mixture of cooled EtOH/H₂O (1:1, v:v). The crude product was recrystallized from acetone/water 9:1 or toluene.

Synthesis of 2,4,5-triarylimidazoles (8a-k) from the benzoin (5)

A 10 mL round-bottom flask equipped with magnetic stirrer was charged with benzoin (5) (1.0 mmol), aldehydes (6a-k) (1.0 mmol), NH₄OAc (7, 4.0 mmol) and CeCl₃.7H₂O (0.10 mmol), followed by EtOH (4 mL). The reaction mixture was stirred and gently refluxed for 4 h. After the completion of the reaction with the monitoring of TLC, 4 mL of water were added. The solid was filtered under reduced pressure and washed with small portions of a mixture of cooled EtOH/H₂O (1:1, v:v). The crude product was recrystallized from acetone/water 9:1 or toluene.

Synthesis of 2,4,5-triaryloxazoles (14a, b) from benzyls (4a, c)

A 10 mL round-bottom flask equipped with magnetic stirrer was charged with benzyls (4a,c) (1.0 mmol), NH₄OAc (7, 5.0 mmol) and SnCl₂.2H₂O (0.05 mmol), followed by EtOH (4 mL). The reaction mixture was stirred and gently refluxed for 4 h. After the completion of the reaction with the monitoring of TLC, 4 mL of water were added. The solid was filtered under reduced pressure and washed with small portions of a mixture of cooled EtOH/H₂O (1:1, v:v). The crude product was recrystallized from acetone/water 9:1 or toluene.

Supplementary Information

Supplementary data (spectral data of compounds 8a-p and 10a, b and spectra) are available free of charge at http://jbcs.org.br as PDF file.

Acknowledgments

The authors would like to acknowledge FAPERGS (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, Grant 2007-6/484615) for financial support and graduate fellowship (M. V. M).

References

1. For reviews on the chemistry of imidazoles, see: Grimmett, M. R. In Comprehensive Heterocyclic Chemistry, vol. 5; Katritzky, A. R.; Rees, C. W., eds.; Pergamon: Oxford, 1984; Grimmett, M. R. In Science of Synthesis, vol. 12; Neier R., ed.; Thieme: Stuttgart, 2002.

2. Palkowitz, A. D.; Steinberg, M. I.; Thrasher, K. J.; Reel, J. K.; Hauser, K. L.; Zimmerman, K. M.; Wiest, S. A.; Whitesitt, C. A.; Simon, R. L.; Pfeifer, W.; Lifer, S. L.; Boyd, D. B.; Barnett, D. J.; Wilson, T. M.; Deeter, J. B.; Kakeuchi, K.; Riley, R. E.; Miller, W. D.; Marshall, W. S.; J. Med. Chem. 1994, 37, 4508.

3. Trujillo, J. I.; Kiefer, J. R.; Huang, W.; Thorarensen, A.; Xing, L.; Caspers, N. L.; Day, J. E.; Mathis, K. J.; Kretzmer, K. K.; Reitz, B. A.; Weinberg, R. A.; Stegeman, R. A.; Wrightstone, A.; Christine, L.; Compton, R.; Li, X.; Bioorg. Med. Chem. Lett. 2009, 19, 908.

4. Linda, L.; Chang, L. L.; Sidler, K. L.; Cascieri, M. A.; Laszlo, S.; Koch, G.; Li, B.; MacCoss, M.; Mantlo, N.; O'Keefe, S.; Pang, M.; Rolandoc, A.; Hagmanna, W. K.; Bioorg. Med. Chem. Lett. 2001, 11, 2549.

5. Sharma, D.; Narasimhan, B.; Kumar, P.; Judge, V.; Narang, R.; Clercq, E.; Balzarini, J.; Eur. J. Med. Chem. 2009, 44, 2347.

6. Kumar, S.; Boehm, J.; Lee, J. C.; Nat. Rev. Drug Disc. 2003, 2, 717.

7. Laufer, S.; Koch, P.; Org. Biomol. Chem. 2008, 6, 437.

8. King, A. J.; Patrick, D. R.; Batorsky R. S.; Ho, M. L.; Do, H. T.; Zhang, S. Y.; Kumar, R.; Rusnak, A. K.; Wilson, D. M.; Hugger, E.; Wang, L.; Karreth, F.; Lougheed, J. C.; Lee, J.; Chau, D.; Stout, T. J.; May, E. W.; Rominger, C. M.; Schaber, M. D.; Luo, L.; Lakdawala, A. S.; Adams, J. L.; Contractor, R. G.; Smalley, K. S. M.; Herlyn, M.; Morrissey, M. M.; Tuveson, D. A.; Huang, P. S.; Cancer Res. 2006, 66, 11100.

9. Young, P. R; McLaughlin, M. M.; Kumari, S.; Kassisi, S.; Doyle, M. L.; McNulty, D.; Gallagher, T. F.; Fisher, S.; McDonnell, P. C.; Carr, S. A.; Huddleston, M. J.; Seibel, G.; Porter, T. G.; Livi, G. P.; Adams, J. L.; Leei, J. C.; J. Biol. Chem. 1997, 272, 12116.

10. Yagi, K.; Soong, C. F.; Irie, M.; J. Org. Chem. 2001, 66, 5419.

11. Fridman, N.; Speiser, S.; Kaftory, M.; Cryst. Growth Des. 2006, 6, 2281.

12. Santos, J.; Mintz, E. A.; Zehnder, O.; Bosshard, C.; Bu, X. R.; Gunter, P.; Tetrahedron Lett. 2001, 42, 805.

13. Japp, F. R.; Robinson, H. H.; Ber. Dtsch. Chem. Ges. 1882, 15, 1268.

14. Radziszewski, B.; Ber. Dtsch. Chem. Ges. 1882, 15, 1493.

15. Davidson, D.; Weiss, M.; Jelling, M.; J. Org. Chem. 1937, 2, 319; Davidson, D.; Weiss, M.; Jelling, M.; J. Org. Chem. 1937, 2, 328.

16. Kamijo, S.; Yamamoto, Y.; Chem. Asian J. 2007, 2, 568.

17. Khodaei, M. M.; Bahrami, K.; Kavianinia, I.; J. Chin. Chem. Soc. 2007, 54, 829.

18. Nagarapu, L.; Apuri, S.; Kantevari, S.; J. Mol. Catal. A: Chem. 2007, 266, 104.

19. Kokare, N. D.; Sangshetti, J. N.; Shinde, D. B.; Synthesis 2007, 2829.

20. Yadhav, S. D.; Kokare, N. D.; Jadhav S. D.; J. Heterocycl. Chem. 2008, 45, 1461.

21. Kantevari, S.; Vuppalapati, S. V. N.; Biradar, D. O.; Nagarapu, L.; J. Mol. Catal. A: Chem. 2007, 266, 109.

22. Shaabani, A.; Rahmati, A.; J. Mol. Catal. A: Chem. 2006, 249, 246.

23. Sadeghi, B.; Mirjalili, B. B. F.; Hashemi, M. M.; Tetrahedron Lett. 2008, 49, 2575.

24. Karimi, A. R.; Alimohammadi, Z.; Azizian, J.; Mohammadi, A. A.; Mohammadizadeh, M. R.; Catal. Commun. 2006, 7, 728.

25. Sivakumar, K.; Kathirvel, A.; Lalitha, A.; Tetrahedron Lett. 2010, 51, 3018.

26. Shih, M.-H.; Tsai, C.-H.; Wang, Y.-C.; Shieh, M.-Y.; Lin, G.-L.; Wei, C.-Y.; Tetrahedron 2007, 63, 2990.

27. Khosropour, A. R.; Ultrason. Sonochem. 2008, 15, 659.

28. Siddiqui, S. A.; Narkhed, U. C.; Palimkar, S. S.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.; Tetrahedron 2005, 61, 3539.

29. Sangshetti, J. N.; Kokare, N. D.; Kotharkar, S. A.; Shinde, D. B.; Monatsh. Chem. 2008, 139, 125.

30. Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R. K.; Ethayathulla, A. S.; Dey, S.; Singh,T. P.; J. Mol. Catal. A: Chem. 2007, 265, 177.

31. Shitole, N. V.; Shelke, K. F.; Sonar, S. S.; Sadaphal, S. A.; Shingate, B. B.; Shingare, M. S.; Bull. Korean Chem. Soc. 2009, 30, 1963.

32. Chary, M. V.; Keerthysri, N. C.; Vupallapati, S. V. N.; Lingaiah, N.; Kantevari, S.; Catal. Commun. 2008, 9, 2013.

33. Wang, L.-M.; Wang, Y.-H.; Tian, H.; Yao, Y.-F.; Shao, J.-H.; Liu, B.; J. Fluorine Chem. 2006, 127, 1570.

34. Sharma, G. V. M.; Jyothi, Y.; Lakshmi, P. S.; Synth. Commun. 2006, 36, 2991.

35. Sun, Y.-F.; Huang, W.; Lu, C.-G.; Cui, Y.-P.; Dyes Pigm. 2009, 81, 10.

36. Sharma, S. D.; Hazarika, P.; Konwar, D.; Tetrahedron Lett. 2008, 49, 2216.

37. Heravi, M. M.; Bakhtiari, K.; Oskooie, H. A.; Taheri, S.; J. Mol. Catal. A: Chem. 2007, 263, 279.

38. Russowsky, D.; Petersen, R. Z.; Godoi, M. N.; Pilli, R. A.; Tetrahedron Lett. 2000, 41, 9939; Andrade, C. K. Z.; Rocha, R. O.; Russowsky, D.; Godoi, M. N.; J. Braz. Chem. Soc. 2005, 16, 535; Godoi, M. N.; Costenaro, H. S.; Kramer, E.; Machado, P. S.; D'Oca, M. G. M.; Russowsky, D.; Quim. Nova 2005, 28, 1010; Silveira, C. C.; Vieira, A. S.; Braga, A. L.; Russowsky, D.; Tetrahedron 2005, 61, 9312; Russowsky, D.; Canto, R. F. S.; Sanches, S. A. A.; D'Oca, M. G. M.; Fatima, A.; Pilli, R. A.; Kohn, L. K.; Antonio, M. A.; de Carvalho, J. E.; Bioorg. Chem. 2006, 34, 173.

39. Russowsky, D.; Lopes, F. A.; Silva, V. S. S.; Canto, K. F. S.; D'Oca, M. G. M.; Godoi, M. N.; J. Braz. Chem. Soc. 2004, 15, 165.

40. Costa, J. S.; Pisoni, D. S.; Silva, C. B.; Petzhold, C. L.; Russowsky, D.; Ceschi, M. A.; J. Braz. Chem. Soc. 2009, 20, 1448.

41. Schwalm, C. S.; Ceschi, M. A.; Russowsky, D.; J. Braz. Chem. Soc. 2011, 22, 623.

42. Chauveau, E.; Marestin, C.; Schiets, F.; Mercier, R.; Green Chem. 2010, 12, 1018.

43. Chary, M. V.; Keerthysri, N. C.; Vupallapati, S. V. N.; Lingaiah, N.; Kantevari, S.; Catal. Commun. 2008, 9, 2013.

44. Lide, D. R.; Handbook of Chemistry and Physics, 79^th ed.; CRC Press: Boca Raton, 1993.

45. Akiyama, T. In Hydrogen Bonding in Organic Synthesis; Pihko, P. M., ed.; Wiley-VCH: Weinheim, 2009, chapter 2.

46. McCairn, M. C.; Culliford, S. J; Kozlowski, R. Z; Sutherland, A. J.; Tetrahedron Lett. 2004, 45, 2163.

47. Epple, R.; Cow, C.; Xie, Y.; Azimioara, M.; Russo, R.; Wang, X.; Wityak, J.; Karanewsky, D. S.; Tuntland, T.; Nguyen-Tran, V. T. B.; Ngo, C. C.; Huang, D.; Saez, E.; Spalding, T.; Gerken, A.; Iskandar, M.; Seidel, H. M.; Tian, S.-S.; J. Med. Chem. 2010, 53, 77.

Submitted: July 6, 2011

Published online: October 11, 2011

Supplementary Information

Spectral characterization of compounds 8a-p and 10a, b

2,4,5-Triphenyl-1H-imidazole (lophine) (8a): solid; mp 278-279 ºC;^{1 1}H NMR (300 MHz, DMSO-d₆) δ 12.71 (br s, 1H, NH), 8.09 (d, 2H, J 7.0 Hz), 7.14-7.70 (m, 13H); ¹³C NMR (75 MHz, DMSO-d₆) δ 145.4, 137.0, 135.1, 131.0, 130.2, 128.6, 129.5, 128.4, 128.2, 128.1, 127.7, 127.0, 126.4, 125.1; IR (Nujol) ν_max/cm^-1 1600, 1503, 1128, 966, 916; GC-MS (IE, 70 eV) m/z (%) 296 (M⁺, 100.0), 165 (48.0), 148 (12.6), 89 (17.1), 77 (7.0), 63 (7.3), 51 (4.0).

4-(4,5-Diphenyl-1H-imidazol-2-yl)phenol (8b): solid; mp 262-263 ºC;^{2 1}H NMR (400 MHz, DMSO-d₆) δ 9.61 (br s, 1H, NH), 7.89 (d, 2H, J 8.3 Hz), 7.05-7.70 (m, 10H), 6.84 (d, 2H, J 8.8 Hz); ¹³C NMR (100 MHz, DMSO-d₆) δ 157.6, 145.9, 126.6, 121.5. 115.2; IR (Nujol) ν_max/cm^-1 1643, 1613, 1546, 1506, 1490, 1240, 764, 698; GC-MS (IE, 70 eV) m/z (%) 312 (M⁺, 100.0), 165 (39.0), 89 (8.9), 77 (8.9), 51 (3.0), 39 (2.9).

2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (8c): solid; mp 233-234 ºC;^{1 1}H NMR (400 MHz, DMSO-d₆) δ 12.45 (br s, 1H, NH), 8.01(d, 2H, J 8.8 Hz), 7.15-7.62 (m, 10H), 7.04 (d, 2H, J 8.8 Hz), 3.82 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 55.1, 59.4, 145.6, 128.2, 126.6, 123.1, 114.0; IR (Nujol) ν_max/cm^-1 1614, 1546, 1248, 765, 696; GC-MS (IE, 70 eV) m/z (%) 326 (M⁺, 100.0), 311 (22.4), 165 (14.0), 89 (6.3), 77 (6.3), 63 (3.0), 51 (2.9), 39 (1.8).

2-(3,4-Dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (8d): solid; mp 250-251 ºC;^{1 1}H NMR (400 MHz, DMSO-d₆) δ 12.46 (br s, 1H, NH), 7.16-7.77 (m, 12H), 7.06 (d, 1H, J 8.3 Hz), 3.86 (s, 3H), 3.82 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 55.4, 55.5, 149.0, 148.7, 148.1, 145.5, 137.8, 129.4, 128.4, 128.2, 128.1, 127.9, 127.4, 126.9, 126.2, 123.1, 117.8, 111.8, 108.9; IR (Nujol) ν_max/cm^-1 1606, 1495, 765, 696; GC-MS (IE, 70 eV) m/z (%) 326 (M⁺, 100.0), 165 (12.6), 89 (5.2),77 (4.8), 63 (5.2), 51 (2.1).

2-(1-Naphtalen-1-yl)-4,5-diphenyl-1H-imidazole (8e): solid; mp 273-275 ºC;^{3 1}H NMR (400 MHz, DMSO-d₆) δ 12.71 (br s, 1H, NH), 8.01 (d, 2H, J 7.8 Hz), 7.98 (dd, 1H, J 7.3 and 1.0 Hz), 7.50-7.65 (m, 7H), 7.20-7.47 (m, 7H); ¹³C NMR (100 MHz, DMSO-d₆) δ 145.4, 137.9, 137.0, 135.2, 133.5, 130.9, 130.2, 129.4, 128.7, 128.4, 128.2, 128.0, 127.7, 127.5, 127.3, 127.0, 126.5, 126.4, 126.3, 125.9, 125.0; IR (Nujol) ν_max/cm^-1 1596, 1500, 764, 695; GC-MS (IE, 70 eV) m/z (%) 326 (M⁺, 100.0), 165 (37.4), 139 (9.3), 89 (6.0), 77 (4.1), 63 (3.3), 51 (1.9).

4-(4,5-Diphenyl-1H-imidazol-2-yl)benzonitrile (8f): solid; mp 248-250 ºC; ¹H NMR (300 MHz, DMSO-d₆) δ 13.03 (br s, 1H, NH), 8.26 (d, 2H, J 8,2 Hz), 7.93 (d, 2H, J 8.2 Hz), 7.18-7.70 (m, 10 H); ¹³C NMR (75 MHz, DMSO-d₆) δ 143.6, 138.0, 134.6, 134.2, 132.7, 130.5, 129.5, 128.6, 128.4, 128.2, 128.0, 127.0, 126.7, 125.4, 118.8, 110.0; IR (Nujol) ν_max/cm^-1 2227, 1610, 1490, 766, 696; GC-MS (IE, 70 eV) m/z (%) 321 (M⁺, 100.0), 165 (47.7), 89 (12.0), 77 (5.3), 63 (7.4), 51 (4.0); HRMS (ESI, w/H⁺) calcd. 321.13387, found 322.13394.

2-(3-Nitrophenyl)-4,5-diphenyl-1H-imidazole (8g): solid; mp 315-317 ºC;^{4 1}H NMR (300 MHz, DMSO-d₆) δ 13.11 (br s, 1H, NH), 8.96 (s, 1H), 8.52 (d, 1H, J 7.7 Hz), 8.21 (dd, 1H, J 8.2 Hz), 7.77 (t, 1H, J 8.0 Hz), 7.22-7.64 (m, 10H); ¹³C NMR (75 MHz, DMSO-d₆) δ 148.3, 143.4, 137.7, 134.7, 131.8, 131.2, 130.6, 130.4, 129.2, 128.7, 128.4, 128.3, 128.1, 127.1, 126.8, 122.6, 119.4; IR (Nujol) ν_max/cm^-1 1541, 1523, 1348, 777, 699; GS-MS (IE, 70 eV) m/z (%) 341 (M⁺, 100.0), 311 (47.8), 295 (21.1), 165 (42.6), 89 (22.0), 77 (13.2), 63 (3.3), 43 (2.2).

2-(2-Nitrophenyl)-4,5-diphenyl-1H-imidazole (8h): solid; mp 224-225 ºC;^{5 1}H NMR (300 MHz, DMSO-d₆) δ 12.98 (sl, 1H, NH), 8.00 (d, 1H, J 7.6 Hz), 7.93 (d, 1H, J 8.2 Hz), 7.79 (t, 1H, J 7.6 Hz), 7.64 (t, 1H, J 7.6 Hz), 7.35-7.60 (m, 8H), 7.31 (t, 1H, J 7.0 Hz), 7.23 (t, 1H, J 7.0 Hz); ¹³C NMR (75 MHz, DMSO-d₆) δ 148.2, 140.9, 137.4, 134.6, 132.0, 130.5, 129.7, 129.4, 128.7, 128.6, 128.2, 128.1, 127.9, 126.9, 126.6, 123.9,123.3; IR (Nujol) ν_max/cm^-1 1601, 1524, 1502, 1364, 724, 694; GC-MS (IE, 70 eV) m/z (%) 341 (M⁺, 59.7), 311 (100.0), 207 (15.0), 165 (40.1), 147 (14.2), 135 (21.3), 104 (79.0), 89 (46.3), 77 (25.6), 63 (13.8), 51 (11.4).

2-(Furan-2-yl)-4,5-diphenyl-1H-imidazole (8i): solid; mp 229-230 ºC;₆¹H NMR (300 MHz, DMSO-d₆) δ 12.85 (br s, 1H, NH), 7.81 (d, 1H, J 1.6 Hz), 7.36-7.75 (m, 10H), 6.98 (d, 1H, J 3.4 Hz), 6.65 (dd, 1H, J 3.4 and 1.8 Hz); ¹³C NMR (75 MHz, DMSO-d₆) δ 148.3, 145.7,143.1, 138.6, 138.0, 129.6, 128.5, 128.3, 127.7, 111.9, 107,5; IR (Nujol) ν_max/cm^-1 1602, 1500, 764, 696; GC-MS (IE, 70 eV) m/z (%) 286 (M⁺, 100.0), 257 (9.4), 165 (22.0), 143 (6.1), 128 (8.6), 89 (3.7), 77 (9.0), 63 (2.8), 51 (12.1).

4,5-Diphenyl-2-(thiophen-2-yl)-1H-imidazole (8j): solid; mp 255-256 ºC;^{1 1}H NMR (300 MHz, DMSO-d₆) δ 12.79 (br s, 1H, NH), 7.69 (d, 1H, J 3.5 Hz), 7.25-7.51 (m, 11H), 7.15 (dd, 1H, J 4.7 and 3.5 Hz); ¹³C NMR (75 MHz, DMSO-d₆) δ 124.1, 126.2, 126.5, 127.0, 127.8, 128.1, 128.6, 130.8, 133.9, 134.7, 136.6, 141.5; IR (Nujol) ν_max/cm^-1 1594, 1493, 765, 695; GC-MS (IE, 70 eV) m/z (%) 304 (6.77), 302 (M⁺, 100.0), 165 (39.7), 151 (8.7), 95 (7.4), 89 (5.8), 77 (6.3), 69 (6.5), 63 (4.1), 51 (4.3).

4,5-Diphenyl-2-(thiophen-3-yl)-1H-imidazole (8k): solid; mp 257-259 ºC; ¹H NMR (300 MHz, DMSO-d₆) δ 12.63 (br s, 1H, NH), 8.04 (dd, 1H, J 2.9 and 1.3), 7.71 (dd, 1H, J 5.0 and 1.2 Hz), 7.65 (dd, 1H, J 5.0 and 2.9 Hz), 7.31-7.53 (m, 10H); ¹³C NMR (75 MHz, DMSO-d₆) δ 142.7, 132.5, 128.4, 127.7,127.0, 125.9, 121.8; IR (Nujol) ν_max/cm^-1 1593, 1493, 765, 697; GC-MS (IE, 70 eV) m/z (%) 304 (6.64), 302 (M⁺, 100.0), 165 (46.6), 151 (8.9), 89 (10.3), 77 (6.5), 63 (5.2), 51 (4.2); HRMS (ESI, w/H⁺) calcd. 303.09505, found 303.09518.

4,5-Bis(4-methoxyphenyl)-2-(thiophen-3-yl)-1H-imidazole (8l): solid; mp 199-201 ºC;^{7 1}H NMR (400 MHz, DMSO-d₆) δ 12.35 (br s, 1H, NH), 7.97 (dd, 1H, J 2.9 and 1.5 Hz), 7.68 (dd, 1H, J 4.8 and 1.1 Hz), 7.62 (dd, 1H, J 5.5 and 2.9 Hz), 6.80-7.50 (m, 8H), 3.75 (s, 3H), 3.79 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 148.3, 143.4, 137.7, 134.7, 131.8, 131.2, 130.6, 130.4, 129.2, 128.7, 128.4, 128.3, 128.1, 127.1, 126.8, 122.6, 119.4; IR (Nujol) ν_max/cm^-1 3391, 1655, 1600, 1573, 1508, 1259, 1163, 842, 832; GC-MS (IE, 70 eV) m/z (%) 362 (M⁺, 100.0), 347 (28.4), 275 (4.1), 181 (5.7).

4,5-Bis(4-fluorophenyl)-2-phenyl-1H-imidazole (8m): solid; mp 255-257 ºC;^{8 1}H NMR (400 MHz, DMSO-d₆) δ 12.67 (br s, 1H, NH), 8.07 (dd, 2H, J 8.4 and 1.1 Hz), 7.50-7.60 (m, 4H), 7.48 (t, 2H, J 7.5 Hz), 7.38 (t, 1H, J 7.3 Hz), 7.29 (t, 2H, J 8.8 Hz), 7.14 (t, 2H, J 8.8 Hz); ¹³C NMR (100 MHz, DMSO-d₆) δ 161.5 (d, ¹J_CF 245.7 Hz), 160.9 (d, ¹J_CF 243.4 Hz), 145.4, 136.1, 131.4 (d, ⁴J_CF 3.1 Hz), 130.4 (d, ³J_CF 8.4 Hz), 130.1, 128.7 (d, ³J_CF 7.6 Hz), 128.5, 128.1, 128.0, 127.2 (d, ⁴J_CF 3.1 Hz), 126.9, 125.0, 115.5 (d, ²J_CF 21.4 Hz), 114.9 (d, ²J_CF 21.4 Hz); IR (Nujol) ν_max/cm^-1 1606, 1590, 1537, 1514, 1595, 1226, 1156, 835; GC-MS (IE, 70 eV) m/z (%) 332 (M⁺, 100.0), 201 (44.1), 89 (9.6), 77 (3.0), 63 (4.6), 51 (2.2), 39 (2.0).

4-[4,5-Bis(4-fluorophenyl)-1H-imidazol-2-yl)]benzonitrile (8n): solid; mp 272-274 ºC; ¹H NMR (400 MHz, DMSO-d₆) δ 12.98 (br s, 1H, NH), 8.23 (d, 2H, J 8.3 Hz), 7.93 (d, 2H, J 8.3 Hz), 7.55 (d, 2H, J 8.8 Hz), 7.54 (d, 2H, J 8.8 Hz), 7.00-7.40 (m, 4H); ¹³C NMR (100 MHz, DMSO-d₆) δ 143.5, 134.0, 132.6, 128.7, 128.0, 125.4, 125.1, 118.6, 110.0; IR (Nujol) ν_max/cm^-1 2229, 1608, 1516, 1497, 1223, 1161, 847, 837; GC-MS (IE, 70 eV) m/z (%) 357 (M⁺, 100.0), 201 (42.5), 107 (13.3); HRMS (ESI, w/H⁺) calcd. 358.11522, found 358.11503.

4,5-Bis(4-fluorophenyl)-2-(furan-2-yl)-1H-imidazole (8o): solid; mp 223-225 ºC; ¹H NMR (400 MHz, DMSO-d₆) δ 12.81 (br s, 1H, NH), 7.79 (dd, 1H, J 1.8 and 0.7 Hz), 7.42-7.58 (m, 4H), 7.27 (t, 2H, J 9.0 Hz), 7.14 (t, 2H, J 9.0 Hz), 6.96 (dd, 1H, J 3.3 and 0.7 Hz), 6.64 (dd, 1H, J 3.3 and 1.8 Hz); ¹³C NMR (100 MHz, DMSO-d₆) δ 161.6 (d, ¹J_CF 244.1 Hz), 161.0 (d, ¹J_CF 241.9 Hz), 145.5, 143.0, 138.4, 136.8, 136.0, 130.4 (d, ³J_CF 8.4 Hz), 128.9 (d, ³J_CF 8.4 Hz), 127.0 (d, ⁴J_CF 3.1 Hz), 126.3, 115.6 (d, ²J_CF 22.1 Hz), 115.0 (d, ²J_CF 21.4 Hz), 111.7, 107.4; IR (Nujol) ν_max/cm^-1 1606, 1529, 1514, 1496, 1228, 1158, 836, 738; GC-MS (IE, 70 eV) m/z (%) 322 (M⁺, 100.0), 293 (11.8), 201 (18.8), 107 (3.9); HRMS (ESI, w/H⁺) calcd. 323.09905, found 323.09912.

4,5-Bis(4-fluorophenyl)- 2-(thiophen-3-yl)-1H-imidazole (8p): solid; mp 255-256 ºC; ¹H NMR (400 MHz, DMSO-d₆) δ 8.17 (dd, 1H, J 2.9 and 1.5 Hz), 7.76 (dd, 1H, J 5.1 and 1.5 Hz), 7.69 (dd, 1H, J 5.1 and 2.9 Hz), 7.54 (dd, 4H, J 9.2 e 5.5 Hz Hz), 7.24 (t, 4H, J 8.8 Hz); ¹³C NMR (100 MHz, DMSO-d₆) δ 166.6 (d, ¹J_CF 248.0 Hz), 166.0 (d, ¹J_CF 255.6 Hz), 162.6, 160.2, 141.9, 132.8, 132.7, 132.6, 129.8 (d, ³J_CF 8.4 Hz), 128.1, 127.1, 152.7, 123.2, 116.5 (d, ²J_CF 22.1 Hz), 115.3 (d, ²J_CF 21.4 Hz); IR (Nujol) ν_max/cm^-1 3467, 1650, 1598, 1501, 1227, 1156, 835; GC-MS (IE, 70 eV) m/z (%) 338 (M⁺, 100.0), 201 (43.7), 107 (11.4), 95 (9.6); HRMS (ESI, w/H⁺) calcd. 339.07620, found 339.07639.

2,4,5-Triphenyl-1,3-oxazole (10a): solid; mp 111-113 ºC;^{9 1}H NMR (200 MHz, DMSO-d₆) δ 8.4-8.0 (m, 2H), 7.3-7.15 (m, 13H); ¹³C NMR (50 MHz, DMSO-d₆) δ 159.9, 145.7, 136.5, 132.3, 131.3, 129.7, 129.5, 129.2, 129.0, 128.6, 128.1, 127.0, 126.6; IR (Nujol) ν_max/cm^-1 3060, 2000-1700, 1600, 1590, 1500, 1490, 700, 690; GC-MS (IE, 70 eV) m/z (%) 297 (M⁺, 100.0), 269 (28.7), 165 (92.9). 105 (9.5), 89 (27.7), 77 (22.7), 63 (14.1), 51 (10.4)

2,4,5-Tris(4-fluorophenyl)-1,3-oxazole (10b): solid; mp 154-157°C; ¹H NMR (200 MHz, DMSO-d₆) δ 8.3-7.9 (m, 2H), 7.8-7.1 (m, 10H); ¹³C NMR (50 MHz, DMSO-d₆) δ 164.2, 162.9, 162.6, 116.9, 116.8, 166.4, 130.4, 129.6, 129.3, 128.7, 125.1, 123.7; IR (Nujol) ν_max/cm^-1 3060, 2100-1700, 1600, 1520, 1500, 1200, 820; GC-MS (IE, 70 eV) m/z (%) 351 (M⁺, 86.6), 323 (18.6), 201 (100.0), 123 (10.5), 107 (28.9), 95 (19.3), 81 (4.4), 51(1.1); HRMS (ESI, w/H⁺) calcd. 352.09922, found 352.0979.

References

1. Sangshetti, J. N.; Kokare, N. D.; Kotharkar, S. A.; Shinde, D. B.; Monatsh. Chem. 2008, 139, 125.

2. Kidwai, M.; Mothsra, P.; Bansal, V.; Somvanshi, R. K.; Ethayathulla, A. S.; Dey, S.; Singh,T. P.; J. Mol. Catal. A: Chem. 2007, 265, 177.

3. Mohammadi, A. A.; Mivechi, M.; Kefayati, H.; Monatsh. Chem. 2008, 139, 935.

4. Zang, H.; Su, Q.; Yingming, M.; Cheng, B.-W.; Jun, S.; Ultrason. Sonochem. 2010, 17, 749.

5. Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S.; Tetrahedron 2009, 65, 10155.

6. Bahrami, K.; Khodaei, M. M.; Nejati, A.; Monatsh. Chem. 2011, 142, 159.

7. Seko, N.; Yoshino, K.; Yokota, K.; Tsukamoto, G.; Chem. Pharm. Bull. 1991, 39, 651.

8. Kamijo, S.; Yamamoto, Y.; Chem. Asian J. 2007, 2, 568.

9. Ramirez, T. A.; Zhao, B.; Shi, Y.; Tetrahedron Lett. 2010, 51, 1822.

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Publication Dates

• Publication in this collection
  02 Feb 2012
• Date of issue
  Jan 2012

History

• Received
  06 July 2011
• Accepted
  11 Aug 2011