Visible light triggered, catalyst free approach for the synthesis of thiazoles and imidazo[2,1-b]thiazoles in EtOH : H₂O green medium

Abstract

The development of a visible light promoted, mild and greener approach for the synthesis of highly functionalized thiazoles and imidazo[2,1-b]thiazoles under photochemical activation in EtOH : H₂O green medium is demonstrated. The characteristic feature of the present protocol is the utilization of visible light (an omnipresent, nontoxic, environmentally benign and inexpensive reagent) to form C–S and C–N bonds and circumvent the use of catalysts or photosensitizers. The reported protocol is the first example of visible light promoted synthesis of thiazoles and imidazo[2,1-b]thiazoles with various attractive features like being catalyst free, eco-efficient and possessing cost effectiveness, short reaction time, excellent yields and sustainability to fulfill the parameters of green chemistry.

---

Introduction

Increasing need is the key to new inventions which lead to new thoughts and new creations. The frequent use of hazardous solvents and metal catalysts in the laboratory pollutes our environment severely. Researchers and scientists are thus shifting their focus towards maximum environmentally benign and sustainable utilization of resources which is capable of being maintained at a steady level without causing ecological damage or exhausting natural resources.¹ The development of visible light mediated synthesis has been recognised as a prominent route for a number of organic transformations² because of its ability to provide activation energy to the reactant in the chemical reactions. Light is an abundant, easily handled, renewable energy source as well as a valuable tool for a myriad of green chemical reactions and thus has attracted much attention.³ Chemists have successfully performed a variety of visible light induced reactions and achieved their goals. Several research groups have used compact fluorescent light (CFL) and light emitting diodes (LEDs) as a visible light source for the formation of the target compound. Easy availability, simple handling, cost effectiveness and a safe approach, places this method under the heading of green chemistry.⁴

There are several organic molecules which are unable to absorb visible light.⁵ To overcome this barrier chemists use photo sensitizers and photo catalysts. In literature different methods have been reported which incorporate the transition metals, certain organic dyes and nanoparticles as a photocatalyst.⁶ However a number of disadvantages associated with transition metal photocatalyst as it shows adverse inherent malignancy, short durability and expensiveness.⁷ At present, many nanoparticles like ZnO/γ-Mn₂O₃,^8a ZnO/CdO,^8b ZnO/V₂O₅,^8c ZnO/Ag/Mn₂O₃ ^8d and electrospun nanomaterials^8e which also act as photocatalytic substances and fruitful for degradation of several textile eluent, organic dyes and organic pollutants. But still nanoparticles exhibit drawbacks as large band gap,^8f depletion of crystallinity^8g which consequence less efficiency. Within this context a catalyst free synthesis using green solvent medium in various synthetic processes has emerged as an important tool.⁹

Thiazole and its derivatives are present in innumerable natural compounds such as in epithilone, thiostrepton, TPP (a coenzyme of Krebs cycle), carboxylase vitamin B1 and antibiotics (penicillin),¹⁰ with significant medicinal and biological importance. Thiazoles are largely associated with medicinal chemistry exhibiting vast applications in drug development for the treatment of allergies,¹¹ inflammation,¹² HIV infections,¹³ hypertension,¹⁴ bacterial infections,¹⁵ hypnotics,¹⁶ schizophrenia¹⁷ and treatment of pain,¹⁸ as new inhibitors of bacterial DNA gyrase B¹⁹ and as fibrinogen receptor antagonists with antithrombotic activity.²⁰ They express tremendous biological activities such as being antitumor,²¹ antifungal,²² antimicrobial,²³ anti-inflammatory,²⁴ antitubercular,²⁵ anticonvulsant,²⁶ diuretic,²⁷ neuroprotective and having antioxidant activity²⁸ (Fig. 1).²⁹

Fig. 1 Some medicinally important derivatives of thiazole and imidazothiazole.^29a–j

Numerous protocols for the synthesis of thiazoles³⁰ and imidazothiazoles³¹ using various types of catalysts and different reaction conditions have been developed. Though the reported methods have several advantages, there are certain drawbacks associated with these methods example long reaction time, use of costly catalyst, difficulty in the recovery of high boiling solvent, low yield of the product, limited availability of starting material, non-reusability of catalyst and solvent. Thus there was a need to design a more eco-efficient method for the synthesis of thiazoles. In continuation of our previous work,³² we were encouraged to develop a more sustainable process for the synthesis of the target scaffold which involved a visible light induced reaction without the use of a catalyst for the completion of the reaction. Mild reaction conditions make it a more relevant, efficient and a cleaner methodology for the synthesis of the target scaffold (Scheme 1).

Scheme 1 Synthesis of thiazoles (3) and (5) derivatives.

For optimization studies of visible light mediated two component synthesis of thiazoles and imidazothiazoles, we carried out two different sets of reactions by the use of phenacyl bromide (1a), N-phenylthiourea (2a) and 2-aminothiazole (4a) as reactants. Condensation of phenacyl bromide (1a, 1 mmol) and N-phenylthiourea (2a, 1 mmol) and condensation of phenacyl bromide (1a, 1 mmol) and 2-aminothiazole (4a, 1 mmol) have been taken as model reactions for the synthesis of different types of thiazoles. During optimization we examined the effect of different solvents, different intensities of light sources and catalysts under different experimental conditions to obtain the best condition for the above transformation (Table 1). In our initial endeavour, we took two reaction mixtures with 1.0 mmol of each reactant in ethanol using CFL (24 W) irradiation as a source of visible light. Under this condition, the condensation of phenacyl bromide (1a) and N-phenyl thiourea (2a) gave the product (3aa) with 85% yield within 10 minutes and condensation of phenacyl bromide (1a) and 2-aminothiazole (4a) afforded the product (5aa) with 55% yield within 5 h (Table 1, entry 8). An interesting result was obtained by the condensation of (1a) and (2a). Immediate formation of product (3aa) took place on addition of second reactant, confirmed by TLC analysis but pure product was formed after 10 minutes. When the same model reactions were performed under catalyst free conditions in a variety of other non-polar traditional organic solvents at rt, they resulted in lower yield of the product. In case of DCM and THF the reaction mixture showed the non-consumption of the starting reactant materials on TLC and resulted in moderate yield of the product (3aa). However, product (5aa) was not formed in case of DCM within 5 h (Table 1, entry 4) and took almost 24 h of CFL irradiation and resulted in trace amount of product (5aa), in case of THF product (5aa) afforded very poor yield of the product (Table 1, entry 2). In case of toluene there was a solubility concern of reactant (2) and that's why it afforded a very low, 15% yield of product (3aa). However product (5aa) was not formed within 5 h and took almost 24 h of CFL irradiation to get the trace amount of the product (5aa). In order to increase the yield of the product we next performed our synthesis in polar solvents like methanol and ethanol. Interestingly there occurred an increase in yield of the product (3aa) and (5aa). Now our complete focus on further improvement of the reaction with respect to time. When we used methanol a small amount of phenacyl bromide (1a) and N-phenyl thiourea (2a) remained unutilized after 10 minutes resulted 80% yield of the product (Table 1, entry 7), moreover the pure product (3aa) was formed after 1 h with 90% yield; while in case of ethanol, a considerable decrease in reaction time was observed and pure product was formed with 85% yield (Table 1, entry 8) within 10 minutes. After that we tried mixed solvent system of EtOH : H₂O to carry out the above transformation and found that EtOH : H₂O solvent system proved successful in increasing the yield of the product (Table 1, entries 9–12). The utility of ethanol and water is to increase the solubility of reactants and in turn, the yield of the product. It is also hypothesized that the transition states of the above reaction would be stabilized by water because of its high static permittivity.³³ The increased yield of product in EtOH : H₂O solvent system may be due to the hydrophobic nature of reactant (1) and (4) in water. This leads to an increase in the number of collisions between reactants and results in increasing their ground state energy as well as the reaction rates. In order to further increase the efficiency of the reaction we used different ratio of EtOH : H₂O solvent system and discovered that (4 : 1) combination gives the best result (Table 1, entry 12). At this stage, in quest of eco-friendlier conditions, both the test reactions were carried out in neat condition without the use of a catalyst.³⁴ No reaction was observed (Table 1, entry 13). A catalyst free synthesis using EtOH : H₂O (4 : 1) as a solvent is a considerably cost effective, safer and environmentally benign method for the above transformation.

Table 1 Optimization table of solvent^a

Entry	Solvent	Time (min)	Yield^b (3aa)	Time (h)	Yield^b (5aa)
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol) in solvent were irradiated under open air at room temperature using CFL (24 W).b Isolated yield of the product (%).c Not detected.
1	Toluene	10	15	5	—^c
2	THF	10	65	5	15
3	Benzene	10	50	5	—^c
4	DCM	10	73	5	—^c
5	DMSO	10	75	5	28
6	CH3CN	10	77	5	Trace
7	Methanol	10	80	5	45
8	EtOH	10	85	5	55
9	EtOH : H2O (1 : 1)	10	86	5	55
10	EtOH : H2O (2 : 1)	10	86	5	57
11	EtOH : H2O (3 : 1)	10	93	5	59
12	EtOH : H2O (4 : 1)	10	95	5	60
13	Neat	10	—^c	5	—^c

---

After the realisation of the best solvent system for the synthesis of thiazoles, we investigated different sources and intensities of visible light irradiation by performing a series of reactions using CFL light (18 W and 20 W) and LEDs (white 7 W). It was found that when we performed the reaction in compact fluorescent lamp (CFL, 24 W) in place of LEDs, the product formed readily (Table 2, entry 1 and 8). However in the absence of visible light, the rate of formation of product significantly decreases (Table 2, entry 2 and 3). We further performed our test reaction with photoredox catalyst, eosin Y which is activated by irradiating visible light. It was seen that although the reaction initially completed a bit faster with 0.5 mol% and 1 mol% of eosin Y, but the difference in final yield of the product was marginal (Table 2, entries 1, 9 and 10). Therefore we selected a catalyst free condition for the required transformation. The presence of oxygen as an oxidant was important for the formation of the desired product since the product was formed in traces in the absence of oxygen (Table 2, entries 4 and 5). Moreover, the reaction was inhibited with benzoquinone (2 mmol) (Table 2, entry 11) in optimized state, which indicates that there may be radical intermediates involved in the reaction.³⁵

Table 2 Optimization table of reaction conditions^a

Entry	Reaction condition	Time (min)	Yield^b (3aa)	Time (h)	Yield^b (5aa)
a Reaction condition: 1a (1.0 mmol), 2a (1.0 mmol) in ethanol : water irradiated using CFL under open air at room temperature.b Isolated yield of the product (%).c Not detected.d 2 mmol.
1	24 W, CFL, air, no catalyst	10	95	5	60
2	Daylight, air, no catalyst	10	43	5	18
3	No light, air, no catalyst	10	34	5	10
4	CFL, degassed	10	54	5	—^c
5	CFL, N2	10	36	5	—^c
6	20 W, CFL, air, no catalyst	10	87	5	52
7	18 W, CFL, air, no catalyst	10	80	5	40
8	White LED (7 W), no catalyst	10	76	5	23
9	CFL, air, eosin Y (0.5 mol%)	10	96	5	60
10	CFL, air, eosin Y (1 mol%)	10	96	5	60
11	CFL, air, benzoquinone^d	10	52	5	16

---

Once the optimal conditions had been finalised the scope and limitations of the developed synthetic strategy was explored by the use of a series of different derivatives of phenacyl bromides (1), thiourea (2) and thiazoles (4). It was observed that the use of phenacyl bromide (1) bearing an electron withdrawing group showed a significant effect on the yield of the product. Similarly, use of thiourea with or without phenyl ring affected the yield of the product; thiourea bearing phenyl ring as a substituent increases the yield of the product, the product being free from the need of purification. In case of thiourea purification is necessary to obtain the pure product and the yield of the product also is less as compared to that in the case of N-phenyl thiourea (Tables 3 and 4).

Table 3 Substrate scope^a (3)

Entry	Phenacyl bromide (1)	Thiourea (2)	Product (3)	Time (min)	Yield^b (%)
a All reactions were carried out in EtOH : H2O (4 : 1) in the presence of visible light irradiation using a 24 W CFL at room temperature under air.b Isolated yield of the product (%).
1	a	a	3aa	08	95
2	a	b	3ab	10	88
3	b	a	3ba	10	85
4	b	d	3bd	10	82
5	b	b	3bb	10	82
6	c	a	3ca	09	87
7	c	b	3cb	09	85
8	d	a	3da	05	96
9	d	b	3db	05	94
10	e	a	3ea	07	94
11	e	c	3ec	07	94
12	e	b	3eb	09	90
13	f	a	3fa	09	89
14	f	b	3fb	10	87
15	f	c	3fc	08	89
16	a	e	3ae	10	81

---

Table 4 Substrate scope^a (5)

Entry	Phenacyl bromide (1)	2-Aminothiazole (4)	Product (5)	Time (h)	Yield^b (%)
a All reactions were carried out in EtOH : H2O (4 : 1) in the presence of visible light irradiation using a 24 W CFL at room temperature under air.b Isolated yield of the product (%).
1	a	a	5aa	5.0	60
2	f	b	5fb	5.5	59
3	d	b	5db	5.0	61
4	g	b	5gb	6.5	50
5	a	c	5ac	6.5	53
6	c	c	5cc	6.5	55
7	e	c	5ec	6.5	53

---

Mechanism

On the basis of literature surey,^36–38 a plausible mechanistic pathway for the synthesis of different types of thiazoles has been proposed. The reaction was initiated by [1,3]tautomerism in reactants (2) and (4). Then visible light promoted homolytic fission of the C–Br bond of phenacyl bromide, S–H bond of N-phenyl thiourea (Scheme 2) and N–H bond of 2-amino thiazole (Scheme 3) takes place resulting to free radicals (A), (B), (C) respectively. After that radical (A) combines with (B) (Scheme 2) and radical (A) combines with (C) (Scheme 3) to give (D) and (E), respectively as mentioned in the mechanism. A homolytic cleavage of carbonyl carbon supported by hydrogen free radical and similar cleavage of N–H bond supported by bromine free radical takes place. Finally the newly formed free radicals (F) and (G) coalesce to form the desired product (3) and (5) via cyclization followed by removal of H₂O molecule.

Scheme 2 Plausible mechanism for the synthesis of thiazole derivatives.

Scheme 3 Plausible mechanism for the synthesis of imidazo[2,1-b]thiazole derivatives.

Conclusion

In summary, we have disclosed a visible-light-induced synthetic strategy to attain a facile synthesis of biologically and medicinally important thiazoles (3) and imidazo-thiazoles (5) via oxidative coupling of phenacyl bromide (1) with thiourea (2) and 2-amino thiazole (4) without the use of heat, base, ligands or an additional oxidant. The present protocol has been applied to the rapid synthesis of products (3) and (5) using commercially available substrates, without the use of hazardous chemicals, catalysts or harsh reaction conditions. The extension of methodology can be examined with a variety of phenacyl bromide derivatives as well as with thiourea and 2-amino thiazole derivatives. Utilization of visible light, eco-efficiency, cost-effectiveness, use of greener reagent, no requirement of bases and catalysts, use of mixed solvent system of EtOH : H₂O, experimental feasibility, short reaction time, easy workup and high yields of the product makes this protocol attractive and superior to the proposed other methods.

Acknowledgements

We sincerely thank SAIF, Punjab University, Chandigarh, for providing micro-analyses and spectra. The author A. Mishra is thankful to UGC, New Delhi, for the award of Junior Research Fellowship (JRF), authors M. Srivastava and P. Rai are thankful to UGC, New Delhi, for the award of Senior Research Fellowship (SRF). B. P. Tripathi and S. Yadav are also thankful to UGC, New Delhi for Research fellowship.

References

1. (a) P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, New York, 1998; (b) M. Eissen, J. O. Metzger, E. Schmidt and V. Schneidewind, Angew. Chem., Int. Ed., 2002, 41, 414; (c) I. T. Horvath, Special Topic Issue on Green Chemistry: Acc. Chem. Res., 2002, 35, 685.
2. (a) G. Ciamician, Science, 1912, 36, 385; (b) A. Albini and M. Fagnoni, Green Chem., 2004, 6, 1.
3. (a) K. Zeitler, Angew. Chem., Int. Ed., 2009, 48, 9785; (b) J. M. R. Narayanam and C. R. Stephenson, Chem. Soc. Rev., 2011, 40, 102.
4. (a) M. A. Ischay, M. E. Anzovino, J. Du and T. P. Yoon, J. Am. Chem. Soc., 2008, 130, 12886; (b) J. M. R. Narayanam, J. W. Tucker and C. R. J. Stephenson, J. Am. Chem. Soc., 2009, 131, 8756.
5. K. Zeitler, Angew. Chem., Int. Ed., 2009, 48, 2.
6. (a) L. Huang and J. Zhao, RSC Adv., 2013, 3, 23377; (b) S. Guo, H. Zhang, L. Huang, Z. Guo, G. Xiong and J. Zhao, Chem. Commun., 2013, 49, 8689; (c) J. Zhao, W. Wu, J. Sun and S. Guo, Chem. Soc. Rev., 2013, 42, 5323; (d) D. Hari, J. Am. Chem. Soc., 2012, 134, 2958; (e) D.-T. Yang, Q.-Y. Meng, J.-J. Zhong, M. Xiang, Q. Liu and L.-Z. Wu, Eur. J. Org. Chem., 2013, 7528; (f) M. Mjek, F. Filace and A. J. V. Wangelin, Beilstein J. Org. Chem., 2014, 10, 981.
7. (a) A. K. Yadav and L. D. S. Yadav, Tetrahedron Lett., 2014, 55, 1788; (b) V. P. Srivastava, A. K. Yadav and L. D. S. Yadav, Synlett, 2014, 625; (c) T. Keshari, V. K. Yadav, V. P. Srivastava and L. D. S. Yadav, Green Chem., 2014, 16, 3986.
8. (a) R. Saravanan, V. K. Gupta, V. Narayanan and A. Stephen, J. Taiwan Inst. Chem. Eng., 2014, 45, 1910; (b) R. Saravanan, H. Shankar, T. Prakash, V. Narayanan and A. Stephen, Mater. Chem. Phys., 2011, 125, 277; (c) R. Saravanan, V. K. Gupta, E. Mosquera and F. Gracia, J. Mol. Liq., 2014, 198, 409; (d) R. Saravanan, M. M. Khan, V. K. Gupta, E. Mosquera, F. Gracia, V. Narayanan and A. Stephen, RSC Adv., 2015, 5, 34645; (e) J. J. Doyle, S. Choudhari, S. Ramakrishna and R. P. Babu, Mater. Sci. Eng., 2013, 33, 91; (f) J. Tian, Z. Zhao, A. Kumar, R. I. Boughtonc and H. Liu, Chem. Soc. Rev., 2014, 43, 6920; (g) M. Pal, U. Pal, R. S. Gonzalez, E. S. Mora and P. Santiago, J. Nano Res., 2009, 5, 193.
9. N. A. A. Ahmad, S. M. Rokade, A. M. Garande and P. M. Bhate, Tetrahedron Lett., 2014, 55, 5458.
10. N. H. Karam, J. H. Tomma and A. H. Al-Dujaili, Chem. Mater., 2013, 3(9), 162.
11. K. D. Haragave, F. K. Hess and J. T. Oliver, J. Med. Chem., 1983, 26, 1158.
12. (a) R. N. Sharma, F. P. Xavier, K. K. Vasu, S. C. Chaturvedi and S. S. Pancholi, J. Enzyme Inhib. Med. Chem., 2009, 24, 890; (b) F. Haviv, J. D. Ratajczyk, R. W. De Net, F. A. Keredesky, R. L. Walters, S. P. Schimidt, J. H. Holmes, P. R. Young and G. W. Carter, J. Med. Chem., 1988, 31, 1719.
13. F. W. Bell, A. S. Cantrell, M. Hoegberg, S. R. Jaskunas, N. G. Johansson, C. L. Jorden, M. D. Kinnick, P. Lind, J. M. Morin Jr, R. Noreen, B. Oberg, J. A. Palkowitz, C. A. Parrish, P. Pranc, C. Sahlberg, R. J. Ternansky, R. T. Vasileff, L. Vrang, S. J. West, H. Zhang and X. X. Zhou, J. Med. Chem., 1995, 38, 4929.
14. W. C. Patt, H. W. Hamilton, M. D. Taylor, M. J. Ryan, D. G. Taylor Jr, C. J. C. Connoly, A. M. Doherty, S. R. Klutchko, I. Sircar, B. A. Steinbaugh, B. L. Batley, C. A. Painchaud, S. T. Rapundalo, B. M. Michniewiez and S. C. J. Olson, J. Med. Chem., 1992, 35, 2562.
15. K. Tsuji and H. Ishikawa, Bioorg. Med. Chem. Lett., 1994, 4, 1601.
16. N. Ergenc, G. Capan, N. S. Gunay, S. Ozkirimli, M. Gungor, S. Ozbey and E. Kendi, Arch. Pharm. Pharm. Med. Chem., 1999, 332, 343.
17. J. C. Jaen, L. D. Wise, B. W. Caprathe, H. Tecle, S. Bergmeier, C. C. Humblet, T. G. Heffner, L. T. Meltzer and T. A. Pugsley, J. Med. Chem., 1990, 33, 311.
18. J. S. Carter, S. Kramer, J. J. Talley, T. Penning, P. Collins, M. J. Graneto, K. Seibert, C. Koboldt, J. Masferrer and B. Zweifel, Bioorg. Med. Chem. Lett., 1999, 9, 1171.
19. J. Rudolph, H. Theis, R. Hanke, R. Endermann, L. Johannsen and F. Geschke, J. Med. Chem., 2001, 44, 619.
20. A. Badorc, M. F. Bordes, P. de Cointet, P. Savi, A. Bernat, A. Lale, M. Petitou, J. P. Maffrand and J. M. Herbert, J. Med. Chem., 1997, 40, 3393.
21. (a) M. M. Ramla, M. A. Omar, A. M. M. El-Khamry and H. I. El-Diwan, Bioorg. Med. Chem., 2006, 14, 7324–7332; (b) M. Popsavin, S. Spaic, M. Svircev, V. Kojic, G. Bogdanovic and V. Popsavin, Bioorg. Med. Chem. Lett., 2007, 17, 4123; (c) E. Gulsory and N. U. Guzeldemirci, Eur. J. Med. Chem., 2007, 42, 320.
22. (a) B. Narayana, K. K. Vijaya Raj, B. V. Ashalatha, N. S. Kumari and B. K. Sarojini, Eur. J. Med. Chem., 2004, 39, 867; (b) P. Beuchet, M. Varache-Lembège, A. Neveu, J. M. Léger, J. Vercauteren, S. Larrouture, G. Deffieux and A. Nuhrich, Eur. J. Med. Chem., 1999, 34, 773; (c) F. Chimenti, B. Bizzarri, E. Maccioni, D. Secci, A. Bolasco, R. Fioravanti, P. Chimenti, A. Granese, S. Carradori, D. Rivanera, D. Lilli, A. Zicari and S. Distinto, Bioorg. Med. Chem. Lett., 2007, 17, 4635.
23. (a) S. N. Pandeya, D. Sriram, G. Nath and E. De Clerq, Eur. J. Pharm. Sci., 1999, 9, 25; (b) M. R. Shiradkar, K. K. Murahari, H. R. Gangadasu, T. Suresh, C. A. Kalyan, D. Panchal, R. Kaur, P. Burange, J. Ghogare, V. Mokale and M. Raut, Bioorg. Med. Chem., 2007, 15, 3997; (c) Z. Xin, Z. Yang-fang, W. Jia, J. Wei, H. Liang and G. Ping, Chem. Res. Chin. Univ., 2006, 22, 459; (d) P. Vicini, A. Geronikaki, K. Anastasia, M. Incerti and F. Zani, Bioorg. Med. Chem., 2006, 14, 3859; (e) O. B. Dundar, O. Ozgen, A. Mentese, N. Altanlar, O. Ath, E. Kendj and R. Ertan, Bioorg. Med. Chem., 2007, 15, 6012; (f) A. Cukurovali, I. Yilmaz, S. Gur and C. Kazaz, Eur. J. Med. Chem., 2006, 41, 201; (g) G. T. Zitouni, Z. A. Kaplancıklı, M. T. Yıldız, P. Chevallet and D. Kaya, Eur. J. Med. Chem., 2005, 40, 607; (h) B. F. Abdel-Wahab, H. A. Abdel-Aziz and E. M. Ahmed, Eur. J. Med. Chem., 2009, 44, 2632; (i) P. Karegoudar, M. S. Karthikeyan, D. J. Prasad, M. Mahalinga, B. S. Holla and N. S. Kumari, Eur. J. Med. Chem., 2008, 43, 261.
24. (a) A. Kumar, C. S. Rajput and S. K. Bhati, Bioorg. Med. Chem., 2007, 15, 3089; (b) B. S. Holla, K. V. Malini, B. S. Rao, B. K. Sarojini and N. S. Kumari, Eur. J. Med. Chem., 2003, 38, 313; (c) R. G. Kalkhambkar, G. M. Kulkarni, H. Shivkumar and N. R. Rao, Eur. J. Med. Chem., 2007, 42, 1272; (d) S. A. F. Rostom, I. M. El-Ashmawy, H. A. Abd El Razik, M. H. Badr and H. M. A. Ashour, Bioorg. Med. Chem., 2009, 17, 882.
25. (a) M. R. Shiradkar, K. K. Murahari, H. R. Gangadasu, T. Suresh, C. A. Kalyan, D. Panchal, R. Kaur, P. Burange, J. Ghogare, V. Mokalec and M. Raut, Bioorg. Med. Chem., 2007, 15, 3997; (b) M. Shiradkar, G. V. S. Kumar, V. Dasari, S. Tatikonda, K. C. Akula and R. Shah, Eur. J. Med. Chem., 2007, 42, 807; (c) G. Aridoss, S. Amirthaganesan, M. S. Kima, J. T. Kim and Y. T. Jeong, Eur. J. Med. Chem., 2009, 44, 4199.
26. (a) K. M. Amin, A. D. E. Rahman and Y. A. Al-Eryani, Bioorg. Med. Chem., 2008, 16, 5377; (b) K. M. Dawood, H. A. Gawad, E. A. Rageb, M. Ellithey and H. A. Mohamed, Bioorg. Med. Chem., 2006, 14, 3672.
27. A. Andreani, M. Rambaldi, G. Mascellani and P. Rugarli, Eur. J. Med. Chem., 1987, 22, 19.
28. (a) M. Koufaki, C. Kiziridi, F. Nikoludaki and M. N. Alexis, Bioorg. Med. Chem. Lett., 2007, 17, 4223; (b) M. H. Shih and K. F. Ying, Bioorg. Med. Chem., 2004, 12, 4633.
29. (a) M. Chatterji, et al., J. Med. Chem., 2014, 57, 6572; (b) L. Hui, L. Zongcheng and A. Thoreleif, Molecules, 2000, 5, 1055; (c) T. Tomasic, S. Katsamakas, Z. Hodnik, J. Ilas, M. Brvar, T. Solmajer, S. M. P. Tammela, M. Banjanac, G. Ergovic, M. Anderluh, L. P. Masic and D. Kikelj, J. Med. Chem., 2015, 58, 5501; (d) F. W. Bell, A. S. Cantrell, M. Hoegberg, S. R. Jaskunas, N. G. Johansson, C. L. Jordon, M. D. Kinnick, P. Lind, J. M. Morin Jr, R. Noreen, B. O’berg, J. A. Palkowitz, C. A. Parrish, P. Pranc, C. Sahlberg, R. J. Ternansky, R. T. Vasileff, L. Vrang, S. J. West, H. Zhang and X.-X. Zhou, J. Med. Chem., 1995, 38, 4929; (e) T. F. A. F. Reji, S. K. C. Devi, K. K. Thomas, K. G. Sreejalekshmi, S. L. Manju and K. N. Rajasekharan, Indian J. Chem., 2008, 47, 1145; (f) T. H. Al-Tel, R. A. Al-Qawasmeh and R. Zaarour, Eur. J. Med. Chem., 2011, 46, 1874; (g) P. Ioan, E. Carosati, M. Micucci, G. Cruciani, F. Broccatelli, B. S. Zhorov, A. Chiarini and R. Budriesi, Curr. Med. Chem., 2011, 18, 4901; (h) E. Carosati, P. Ioan, M. Micucci, F. Broccatelli, G. Cruciani, B. S. Zhorov, A. Chiarini and R. Budriesi, Curr. Med. Chem., 2012, 19, 4306; (i) A. M. Frag, A. S. Mayhoub, S. E. Barakat and A. H. Bayomi, Bioorg. Med. Chem., 2008, 16, 4569; (j) N. Y. Wang, Y. Xu, W. Q. Zuo, K. J. Xiao, L. Liu, X. X. Zeng, X. Y. You, L. D. Zhang, C. Gao, Z. H. Liu, T. H.Ye, Y. Xia, Y. Xiong, X. J. Song, Q. Lei, C. T. Peng, H. Tang, S. Y. Yang, Y. Q. Wei and L. T. Yu, J. Med. Chem., 2015, 58, 2764.
30. (a) J. V. Madhav, B. S. Kuarm and B. Rajitha, Synth. Commun., 2008, 38, 3514; (b) B. Das, V. S. Reddy and R. Ramu, J. Mol. Catal. A: Chem., 2006, 252, 235; (c) D. Goff and J. Fernandez, Tetrahedron Lett., 1999, 40, 423; (d) M. Narender, M. Somi Reddy, V. P. Kumar, V. P. Reddy, Y. V. D. Nageswar and K. R. Rao, J. Org. Chem., 2007, 72, 1849; (e) U. Bhoga, Eur. J. Med. Chem., 2007, 42, 1144; (f) J. Banothu, K. Vaarla, R. Bavantula and P. A. Crooks, Chin. Chem. Lett., 2014, 25, 172; (g) V. Narsaiah, R. S. Ghogare and D. O. Biradar, Org. Commun., 2011, 4, 75; (h) T. M. Potewar, S. A. Ingale and K. V. Srinivasan, Tetrahedron, 2008, 64, 5019; (i) D. Zhu, J. Chen, H. Xiao, M. Liu, J. Ding and H. Wu, Synth. Commun., 2009, 39, 2895; (j) T. M. Potewar, S. A. Ingale and K. V. Srinivasan, ARKIVOC, 2008, 12, 117.
31. (a) S. Mishra, K. Monir, S. Mitra and A. Hajra, Org. Lett., 2014, 16, 6084; (b) S. Kamila, K. Mendoza and E. R. Biehl, Tetrahedron Lett., 2012, 53, 4921; (c) I. M. Mahdavi, M. Asadi, M. Saeedi, M. Ebrahimi, M. A. Rasouli, P. R. Ranjbar, A. Foroumadi and A. Shafiee, Synthesis, 2012, 44, 3649; (d) S. Kumar and D. P. Sahu, ARKIVOC, 2008, xv, 88.
32. (a) M. Srivastava, P. Rai, J. Singh and J. Singh, RSC Adv., 2013, 3, 16994; (b) M. Srivastava, P. Rai, J. Singh and J. Singh, New J. Chem., 2014, 38, 302; (c) S. Yadav, M. Srivastava, P. Rai, J. Singh and J. Singh, New J. Chem., 2015, 39, 4556; (d) S. Yadav, M. Srivastava, P. Rai, J. Singh and J. Singh, Tetrahedron Lett., 2015, 56, 5831.
33. (a) M. C. Pirrung, Chem.–Eur. J., 2006, 12, 1312; (b) T. S. Shaikh, J. D. Patil, D. S. Gaikwad, P. G. Hegade, P. B. Patil, K. A. Undale, M. M. Mane and D. M. Pore, Indian J. Chem., 2014, 53, 1288.
34. C. Bodhak, A. Kundu and A. Pramanik, RSC Adv., 2015, 5, 85202.
35. M. Pelaez, et al., Appl. Catal., B, 2012, 125, 331.
36. V. P. Srivastava, A. K. Yadav and L. D. S. Yadav, Synlett, 2013, 24, 465.
37. A. T. Veetil, T. Solomek, B. P. Ngoy, N. Pavlíkova, D. Heger and P. Klan, J. Org. Chem., 2011, 76, 8232.
38. J. Renaud and J. C. Scaiano, Can. J. Chem., 1996, 74, 1724.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra05385h

---