Use of a novel multicomponent reaction under high pressure for the efficient construction of a new pyridazino[5,4,3-de][1,6]naphthyridine tricyclic system

Abstract

A novel multicomponent reaction between the 2-phenylhydrazono derivative 1a, malononitrile and aromatic aldehydes or acetone, carried out under high pressure, was found to generate pyridazino[5,4,3-de][1,6]naphthyridine derivatives 9a–h and 22. The structures of the products were established by using X-ray crystallographic methods. Mechanisms to account for product formation are proposed.

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Introduction

Developing methods to synthesize novel polyfunctional heterocycles remains a major goal of industrial and academic organic chemists^1–10 because these substances serve as potential pharmaceuticals,^1–4 agrochemicals,^4–6 dye intermediates^7,8 and constituents of cosmetics products.^9,10

Driven by an interest in devising methods for synthesizing heterocycles, Elnagdi et al. in the 1980s described a protocol for synthesizing pyridazinone derivatives 4a–e which reacted with benzylidenemalononitrile afforded phthalazine derivatives 5 that utilizes reaction of 2-phenylhydrazones 1a–e with ethylcyanoacetate (2a) in AcOH/NH₄OAc.^22–25 Subsequently, Abdelrazek reported the synthesis of 3f using a similar approach. Pyridazinones 4a–e have been extensively utilized as precursors of condensed biologically relevant heterocyclic compounds 5–7 (Scheme 2),^26–32 several of which have been patented as protein tyrosine phosphatase (PTPase) inhibitors and as drugs for treatment of amyloid diseases (Scheme 1).^33–35

Scheme 1 Syntheses of compounds 3f and 4a–e.

Scheme 2 Syntheses of 5–7.

In recent years, increasing attention has been given to green synthetic methods, which emphasize the use of recyclable reagents and catalysts,^11,12 and new procedures such as solventless,¹³ domino¹⁴ and multicomponent reactions (MCRs),^15–18 and processes that utilize microwave (MW) irradiation, ultrasound (US) and light as alternative energy sources.^19–21 Stimulated by an aim to develop green methods, Al-Mousawi et al. utilized MW irradiation in heterocycle synthesis, and found that this method leads to increased reaction rates.³⁶

It has been established that MW irradiation results in the formation of hot spots in the reaction mixture and that the higher temperatures enhance rates in the normal manner.³⁷ Because microwave ovens are relatively expensive and their use for scaled-up reactions is difficult,³⁸ high-pressure techniques for accelerating reactions have gained the attention of organic chemists since the mid-1970s. This technique has been employed to promote Diels–Alder, Biginelli and Michael addition reactions.^39,40 The effects of high pressure are associated with reactions being characterized by a volume of activation (ΔV^#), defined as the difference between the volume occupied by the reactants and that occupied by the transition state. The application of high pressure in reactions with large negative values of ΔV^# has a rate-accelerating effect. High pressures can also influence the equilibrium, regiochemistry and stereochemistry of processes, as well as the reaction mechanism.⁴¹

Taking into account these observations, we decided to investigate the potential utility of high pressure on heterocycle-forming multicomponent reactions. Specifically, we performed base-catalysed multicomponent reactions (MCRs) of 2-phenylhydrazone derivatives (1a), malononitrile (2) and aromatic aldehydes that produced pyridazine derivative 4 or 5 under high pressure. The results of this effort, which led to the development of a new method to prepare previously unreported pyridazino[5,4,3-de][1,6]naphthyridine derivatives, are described below.

Results and discussion

Multicomponent reactions of 1a (0.01 mol) with aromatic aldehydes 8a–h and malononitrile 2b (0.02 mol) in dioxane containing piperidine (3–5 mL) were performed under high pressure in a Q-Tube™ pressure reactor. The mixtures were heated in an oil bath at 120 °C for 20–25 min. The solids obtained upon cooling were collected by filtration and crystallized from an appropriate solvent. These processes were observed to take place efficiently to produce the corresponding pyridazino[5,4,3-de][1,6]naphthyridines 9a–h (Scheme 3, Table 1). The structures of the products were assigned using ¹H NMR spectroscopy and that of 9d was confirmed by X-ray crystallographic analysis (Fig. 1). It is believed that a possible mechanistic pathway for this process involved initial condensation of 1a with malononitrile 2b to form hydrazone ester 11 (Scheme 4), which subsequently condensed with the aldehydes 8a–h to generate the conjugated derivatives 12a–h, respectively. Cyclization of 12a–h to form 13a–h was, according to this mechanism, followed by reaction of 13a–h with malononitrile to form intermediates 14a–h, which then cyclized to produce 9a–h, respectively.

Scheme 3 Syntheses of 9a–h.

Table 1 Yields of 9a–h from reactions of 1a with aromatic aldehydes 8a–h and malononitrile 2b

Entry	Ar	Yield (%)
9a	Ph	85
9b	4-ClC6H4	73
9c	2-ClC6H4	65
9d	4-CH3C6H4	80
9e	2-CH3C6H4	76
9f	4-O2NC6H4	50
9g	2-Furyl	72
9h	4-Pyridine	73

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Fig. 1 Ortep plot of X-ray crystal structure of 9d.

Scheme 4 Suggested mechanism for the formation of 9a–h.

According to an alternative mechanism for this process, malononitrile 2b first dimerized to form 15, which condensed with 1a to generate 16. Conjugated polynitrile 16, according to this alternative mechanism, condensed with aromatic aldehydes 8a–h before cyclization to afford 17a–h, which then cyclized to afford 18a–h (pathway A). Alternatively, 16 may have cyclized to form 19, which then condensed with aromatic aldehydes 8a–h to afford 18a–h, respectively (pathway B) (Scheme 5, Fig. 2). Both routes ended with the formation of 9a–h.

Scheme 5 Synthesis of compound 20, and two pathways for forming compounds 9a–h.

Fig. 2 Ortep plot of X-ray crystal structure of 20.

However, pathway B in this mechanistic scenario is less likely because the reaction of 1a with malononitrile in a 1 : 2 molar ratio was observed to produce the aryl-azopyridine derivative 20, whose structure was determined by using X-ray crystallographic analysis. However, the suggested mechanisms outlined in Scheme 4 and in Scheme 5 pathway A are both reasonable and difficult to distinguish.

In a similar manner, the one-pot multicomponent reaction of the 2-phenylhydrazono derivative 1a, malononitrile 2b and acetone 21 under high-pressure conditions in dioxane and with piperidine as the base catalyst afforded the pyridazino[5,4,3-de][1,6]naphthyridine derivative 22, whose structure was determined by using X-ray crystallographic analysis (Scheme 6, Fig. 3).

Scheme 6 Synthesis of compound 22.

Fig. 3 Ortep plot of X-ray crystal data of 22.

Conclusion

In the efforts described above, we developed a novel multicomponent reaction between 2-phenylhydrazono derivative 1a, malononitrile and aromatic aldehydes or acetone, which was carried out under high pressure and generated pyridazino[5,4,3-de][1,6]naphthyridine derivatives (9a–h, 22).

Experimental section

General

Melting points are reported uncorrected and were determined with a Sanyo (Gallenkamp) instrument. Infrared spectra were recorded using KBr pellets and a Jasco FT-IR 6300 instrument and absorption bands are reported in cm⁻¹. ¹H- and ¹³C-NMR spectra were determined by using a Bruker DPX instrument at 400 MHz or 600 MHz for ¹H-NMR and 100 MHz for ¹³C-NMR, and either CDCl₃ or DMSO-d6 solutions with TMS as internal standards. Chemical shifts are reported in ppm. Mass spectra and accurate mass measurements were made using a GCMS DFS Thermo spectrometer in the EI (70 eV) mode. X-ray crystallographic structure analyses were performed by using Rigaku Rapid II and Bruker X8 Prospector single-crystal X-ray diffractometers. CCDC 1496260 for compound 9d, CCDC 1496321 for compound 20 and CCDC 1496261 for compound 22.† All reactions were monitored by using TLC with 1 : 1 ethyl acetate–petroleum ether as the eluent and were carried out until starting materials were completely consumed.

General procedure for the Q-Tube™-assisted synthesis of compounds 9a, h, 20 and 22

Reactions to form compounds 9a, h, 20 and 22 were performed in a 35 mL Q-Tube™ pressure reactor obtained from Q-Labtech, equipped with a cap/sleeve, pressure adapter (120 psi), needle adapter/needle, borosilicate glass tube, Teflon septum, and catch bottle. A mixture of compound 1a (0.01 mol), malononitrile 2b (0.02 mol) and aromatic aldehydes 8a–h for synthesis of compounds 9a–h or acetone (21) (0.01 mol) for synthesis of compound 22 in the presence of dioxane as a solvent and piperidine (3–5 mL) as a base catalyst were sequentially added into the Q-Tube™ pressure reactor. A Teflon septum was placed on the top of each tube, and an appropriate cap and pressure adapter were used. The mixture was heated in an oil bath at 120 °C. After 20–25 minutes, following completion of the reaction, the mixture was cooled and poured into ice-water (50 mL). The resulting solid was collected by filtration and crystallized from the appropriate solvent.

Ethyl 8-amino-7-cyano-1,5-diphenyl-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9a). 9a was crystallized from acetic acid to form yellow crystals, yield 85%; mp 312–14 °C; anal. calcd for C₂₅H₁₈N₆O₂: C, 69.11; H, 4.18; N, 19.34. Found: C, 69.15; H, 4.21; N, 19.50; EI-HRMS: m/z = 434.1486 (MH⁺); C₂₅H₁₈N₆O₂ requires: m/z = 434.1486 (MH⁺); IR: 3311, 3210 (NH₂), 2216 (CN), 1712 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.36 (t, 3H, J = 8.0 Hz, CH₃), 4.42 (q, 2H, J = 8.0 Hz, CH₂), 7.22 (br, 2H, NH₂, D₂O exchangeable), 7.51–8.20 (m, 11H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.1, 161.5 (2C), 154.8, 150.7, 141.5, 138.0, 134.4, 131.9, 130.5, 129.1 (2C), 129.0 (2C), 128.9, 127.2 (2C), 126.7 (2C), 116.5, 110.0, 104.2, 74.5, 61.8, 14.0. MS: m/z (%) 434 (M⁺, 100), 361 (65), 334 (5), 295 (5), 216 (5), 189 (5), 77 (15).

Ethyl 8-amino-5-(4-chlorophenyl)-7-cyano-1-phenyl-1H-pyridazino[5,4,3-de][1,6]-naphthyridine-3-carboxylate (9b). 9b was crystallized from dimethylformamide dimethylacetal (DMF) to form yellow crystals, yield 73%; mp 314–16 °C; anal. calcd for C₂₅H₁₇N₆ClO₂: C, 64.04; H, 3.65; N, 17.92. Found: C, 64.10; H, 3.62; N, 18.01; EI-HRMS: m/z = 468.1093 (MH⁺); C₂₅H₁₇N₆ClO₂ requires: m/z = 468.1096 (MH⁺); IR: 3339, 3231 (NH₂), 2206 (CN), 1708 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.36 (t, 3H, J = 8.0 Hz, CH₃), 4.43 (q, 2H, J = 8.0 Hz, CH₂), 7.00 (br, 2H, NH₂, D₂O exchangeable), 7.50–8.19 (m, 10H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.8, 162.1, 161.5, 160.2, 145.7, 150.7, 141.4, 136.7, 135.4, 134.3, 132.1, 129.0 (4C), 128.9 (2C), 126.6 (2C), 116.4, 110.2, 104.1, 74.5, 61.7, 14.0. MS: m/z (%) 468 (M⁺, 90), 395 (100), 368 (10), 333 (10), 295 (10), 242 (10), 204 (10), 166 (10), 118 (10), 93 (10), 77 (90).

Ethyl 8-amino-5-(2-chlorophenyl)-7-cyano-1-phenyl-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9c). 9c was crystallized from acetic acid to form yellow crystals, yield 65%; mp 318–20 °C; anal. calcd for C₂₅H₁₇N₆ClO₂: C, 64.04; H, 3.65; N, 17.92. Found: C, 64.19; H, 3.55; N, 17.87; EI-HRMS: m/z = 468.1096 (MH⁺); C₂₅H₁₇N₆ClO₂ requires: m/z = 468.1096 (MH⁺); IR: 3317, 3210 (NH₂), 2215 (CN), 1724 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.29 (t, 3H, J = 8.0 Hz, CH₃), 4.36 (q, 2H, J = 8.0 Hz, CH₂), 7.23 (br, 2H, NH₂, D₂O exchangeable), 7.52–7.89 (m, 10H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.4, 162.0, 161.5, 154.7, 150.9, 141.5, 138.8, 134.0, 131.4, 131.1, 131.0, 130.0, 129.1 (2C), 128.9, 127.5, 126.7 (2C), 116.5, 110.0, 108.7, 74.4, 61.7, 14.0. MS: m/z (%) 468 (M⁺, 100), 395 (60), 370 (5), 333 (5), 295 (10), 242 (5), 214 (5), 93 (5), 77 (25).

Ethyl 8-amino-7-cyano-1-phenyl-5-(p-tolyl)-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9d). 9d was crystallized from acetic acid to form yellow crystals, yield 80%; mp 313–15 °C; anal. calcd for C₂₆H₂₀N₆O₂: C, 69.63; H, 4.50; N, 18.74. Found: C, 69.58; H, 4.59; N, 18.78; EI-HRMS: m/z = 448.1643 (MH⁺); C₂₆H₂₀N₆O₂ requires: m/z = 448.1642 (MH⁺); IR: 3330, 3222 (NH₂), 2201 (CN), 1711 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.33 (t, 3H, J = 8.0 Hz, CH₃), 2.09 (s, 3H, CH₃), 4.42 (q, 2H, J = 8.0 Hz, CH₂), 7.16 (br, 2H, NH₂, D₂O exchangeable), 7.37–8.11 (m, 10H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.1, 161.5, 161.4, 154.7, 150.6, 141.5, 140.4, 135.2, 134.3, 131.8, 129.5 (2C), 129.0 (2C), 128.8, 127.1 (2C), 126.6 (2C), 116.5, 109.8, 103.9, 74.5, 61.7, 20.2, 14.0. MS: m/z (%) 448 (M⁺, 95), 375 (100), 348 (5), 309 (5), 230 (5), 187 (10), 118 (5), 91 (10), 77 (35).

Ethyl 8-amino-7-cyano-1-phenyl-5-(o-tolyl)-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9e). 9e was crystallized from DMF to form orange crystals, yield 76%; mp 290–92 °C; anal. calcd for C₂₆H₂₀N₆O₂: C, 69.63; H, 4.50; N, 18.74. Found: C, 69.60; H, 4.61; N, 18.80; EI-HRMS: m/z = 448.1642 (MH⁺); C₂₆H₂₀N₆O₂ requires: m/z = 448.1642 (MH⁺); IR: 3330, 3222 (NH₂), 2208 (CN), 1721 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.29 (t, 3H, J = 8.0 Hz, CH₃), 2.44 (s, 3H, CH₃), 4.36 (q, 2H, J = 8.0 Hz, CH₂), 7.19 (br, 2H, NH₂, D₂O exchangeable), 7.37–7.75 (m, 10H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 165.4, 162.1, 161.4, 145.4, 150.7, 141.5, 139.7, 135.8, 134.1, 131.3, 130.9, 129.3, 129.1 (2C), 129.0, 128.8, 126.6 (2C), 126.0, 116.5, 109.4, 108.1, 74.4, 61.7, 20.3, 13.9. MS: m/z (%) 448 (M⁺, 25), 375 (100), 348 (10), 255 (5), 201 (5), 187 (15), 91 (5), 77 (20).

Ethyl 8-amino-7-cyano-5-(4-nitrophenyl)-1-phenyl-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9f). 9f was crystallized from DMF to form yellow crystals, yield 50%; mp 318–19 °C; anal. calcd for C₂₅H₁₇N₇O₄: C, 62.63; H, 3.57; N, 20.45. Found: C, 62.61; H, 3.59; N, 20.42; EI-HRMS: m/z = 479.1336 (MH⁺); C₂₅H₁₇N₇O₄ requires: m/z = 479.1337 (MH⁺); IR: 3428, 3324 (NH₂), 2219 (CN), 1720 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.34 (t, 3H, J = 8.0 Hz, CH₃), 4.42 (q, 2H, J = 8.0 Hz, CH₂), 7.32 (br, 2H, NH₂, D₂O exchangeable), 7.52–8.46 (m, 10H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.1, 161.6, 154.0, 154.7, 150.7, 148.4, 143.8, 141.4, 134.1, 132.2, 129.1 (2C), 128.9, 128.4 (2C), 126.6 (2C), 124.1 (2C), 116.3, 110.7, 105.1, 74.5, 61.8, 14.0. MS: m/z (%) 479 (M⁺, 100), 449 (5), 433 (5), 406 (20), 368 (10), 360 (15), 334 (5), 284 (10), 256 (5), 185 (10), 129 (10), 83 (15), 73 (20).

Ethyl 8-amino-7-cyano-5-(furan-2-yl)-1-phenyl-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9g). 9g was crystallized from DMF to form brown crystals, yield 72%; mp 320–22 °C; anal. calcd for C₂₃H₁₆N₆O₃: C, 65.09; H, 3.80; N, 19.80. Found: C, 65.15; H, 3.77; N, 19.85; EI-HRMS: m/z = 424.1278 (MH⁺); C₂₃H₁₆N₆O₃ requires: m/z = 424.1278 (MH⁺); IR: 3484, 3381 (NH₂), 2206 (CN), 1707 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.32 (t, 3H, J = 8.0 Hz, CH₃), 4.38 (q, 2H, J = 8.0 Hz, CH₂), 6.74 (m, 1H, furyl-H), 7.15 (br, 2H, NH₂, D₂O exchangeable), 7.26–7.99 (m, 8H, Ar-H, furyl-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.1, 161.5, 154.8, 153.3, 152.7, 150.5, 145.9, 141.5, 134.0, 131.9, 129.0 (2C), 128.8, 126.7 (2C), 116.4, 112.8, 112.1, 109.8, 102.4, 74.2, 61.7, 14.0. MS: m/z (%) 424 (M⁺, 100), 351 (70), 323 (5), 295 (10), 205 (5), 129 (5), 93 (5), 77 (20).

Ethyl 8-amino-7-cyano-1-phenyl-5-(pyridin-4-yl)-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (9h). 9h was crystallized from DMF to form brown crystals, yield 73%; mp 306–08 °C; anal. calcd for C₂₄H₁₇N₇O₂: C, 66.20; H, 3.94; N, 22.52. Found: C, 66.25; H, 3.85; N, 22.59; EI-HRMS: m/z = 435.1438 (MH⁺); C₂₄H₁₇N₇O₂ requires: m/z = 435.1438 (MH⁺); IR: 3390, 3306 (NH₂), 2201 (CN), 1710 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.34 (t, 3H, J = 8.0 Hz, CH₃), 4.41 (q, 2H, J = 8.0 Hz, CH₂), 7.24 (br, 2H, NH₂, D₂O exchangeable), 7.50–8.56 (m, 10H, Ar-H, pyridine-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.1, 161.5, 160.1, 154.7, 150.6, 139.0, 136.7, 134.2, 132.1 (2C), 130.0, 129.7 (2C), 129.1, 129.1, 129.0, 126.6, 114.0, 113.0, 110.1, 82.2, 74.5, 61.8, 14.0. MS: m/z (%) 435 (M⁺, 100), 362 (55), 335 (5), 77 (5).

Synthesis of 2-(3-cyano-4-methyl-6-oxo-5-(2-phenylhydrazono)-5,6-dihydropyridin-2(1H)-ylidene)malononitrile (20). The reaction to form 20 was performed in a 35 mL Q-Tube™ pressure reactor obtained from Q-Labtech, equipped with a cap/sleeve, pressure adapter (120 psi), needle adapter/needle, borosilicate glass tube, Teflon septum, and catch bottle. A mixture of the compounds ethyl-3-oxo-2-(2-phenylhydrazono)butanoate 1a (2.34 g, 0.01 mol) and malononitrile 2b (1.3 g, 0.02 mol) in dioxane and piperidine (3–5 mL) as the base catalyst were sequentially added into the Q-Tube™ pressure reactor. A Teflon septum was placed on the top of the tube, and an appropriate cap and pressure adapter were used. The mixture was heated in an oil bath at 120 °C. After 20–25 min, the reaction mixture, which was monitored by TLC, was stopped. The reaction mixture was cooled and poured into ice-water (50 mL). The solids were collected by filtration and crystallized from DMF to form red crystals, yield 82%; mp 332–34 °C; anal. calcd for C₁₆H₁₀N₆O: C, 63.57; H, 3.33; N, 27.80. Found: C, 63.62; H, 3.28; N, 27.85; EI-HRMS: m/z = 302.0910 (MH⁺); C₁₆H₁₀N₆O requires: m/z = 302.0911 (MH⁺); IR: 3100 (NH), 3110 (NH), 2215 (3CN), 1662 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 2.50 (s, 3H, CH₃), 7.35–7.77 (m, 7H, Ar-H, 2NH–H); ¹³C NMR (100 MHz, DMSO-d6): δ = 161.4, 158.7, 154.5, 141.5, 129.5 (2C), 129.6, 128.0, 124.6, 118.3 (2C), 113.8, 94.8 (2C), 53.5, 16.5. MS: m/z (%) 302 (M⁺, 100), 285 (15), 274 (5), 197 (5), 142 (5), 105 (5), 93 (25), 77 (50).

Ethyl 8-amino-7-cyano-5,5-dimethyl-1-phenyl-5,6-dihydro-1H-pyridazino[5,4,3-de][1,6]naphthyridine-3-carboxylate (22). Compound 22 was crystallized from ethanol to form red crystals, yield 80%; mp 282–84 °C; anal. calcd for C₂₁H₂₀N₆O₂: C, 64.94; H, 5.19; N, 21.64. Found: C, 64.91; H, 5.25; N, 21.59; EI-HRMS: m/z = 388.1646 (MH⁺); C₂₁H₂₀N₆O₂ requires: m/z = 388.1645 (MH⁺); IR: 3454 (NH), 3367, 3334 (NH₂), 2193 (CN), 1713 (CO); ¹H NMR (400 MHz, DMSO-d6): δ = 1.22 (t, 3H, J = 8.0 Hz, CH₃), 1.34 (s, 6H, 2CH₃), 4.21 (q, 2H, J = 8.0 Hz, CH₂), 5.41 (s, 1H, NH, D₂O exchangeable), 6.43 (br, 2H, NH₂, D₂O exchangeable), 6.9 (s, 1H, Ar-H), 7.30–7.41 (m, 5H, Ar-H); ¹³C NMR (100 MHz, DMSO-d6): δ = 162.5, 160.3, 150.5, 146.5, 141.7, 135.6, 128.4 (2C), 126.9, 126.6 (2C), 116.5, 115.9, 111.7, 91.2, 67.6, 60.9, 53.1, 31.4 (2C), 13.9. MS: m/z (%) 388 (M⁺, 10), 373 (100), 301 (20), 284 (5), 274 (15), 273 (5), 245 (5), 208 (5), 181 (5), 150 (10), 55 (15).

Acknowledgements

The authors are grateful to the Kuwait University Research Administration for financial support of project SC12/13. Analytical facilities provided by GFS projects No. GS 01/01, GS 01/03, GS 01/05, GS 02/10 & GS 03/08 are greatly appreciated.

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1496260, 1496261 and 1496321. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra19535k

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