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A Facile Entry for One-pot Synthesis of 5,7-Diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles

5,7-Diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino [3,4-d]-1,2,3-selenadiazoles의 손쉬운 One-pot 합성

  • Gopalakrishnan, M. (Synthetic Organic Chemistry Laboratory, Department of Chemistry, Annamalai University) ;
  • Thanusu, J. (Synthetic Organic Chemistry Laboratory, Department of Chemistry, Annamalai University) ;
  • Kanagarajan, V. (Synthetic Organic Chemistry Laboratory, Department of Chemistry, Annamalai University)
  • Published : 2008.02.20
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Abstract

A simple synthetic strategy is described for one-pot synthesis of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles (11-15) in the presence of NaHSO4.SiO2 as a heterogeneous catalyst in dry media under microwave irradiation.Key words: One-pot synthesis, 3,3-Dimethyl-2,6-diarylpiperidin-4-one; 1,2,3-Selenadiazoles; Selenium dioxide; NaHSO4.SiO2 Heterogeneous catalyst.

조사 아래 불균일촉매 NaHSO4.SiO2의 존재하에서 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino [3,4-d]-1,2,3-selenadiazoles의 one-pot.

Keywords

INTRODUCTION

Coupling of dry media synthesis with microwave activation is one of the novel approaches to ecofriendly chemistry. Reports about synthesizing selenium-containing heterocycles are relatively rare,1,2 although some of them are used as chemotherapeutic agents.3,4 In addition, organoselenium reagents5,6 are now commonly used as a powerful tool for introducing new functional groups into organic substrates. Piperidin-4-one nucleus have received extensive attention in the past and recent years because of their diverse biological activities, including antiviral, antitumour,7,8 central nervous system,9 local anesthetic,10 anticancer,11 and antimicrobial activity12 and their derivative piperidine are also biologically important and act as neurokinin receptor antagonists,13 analgesic and anti-hypertensive agents.14 In recent years there has been a great deal of interest in exploiting more than one proximal functional groups for designing novel structures capable of performing a variety of functions. One such functionality is α-keto methylene group, which has been used as a building block for 1,2,3-selenadiazoles.

Microwave-induced rate acceleration technology15-17 has become powerful tool in organic synthesis in view of the mild, clean, and convenient methodology and the enhanced selectivity of the reaction processes in comparison to conventional solution reactions, and the associated ease of manipulation. Chemical reactions are accelerated essentially because of selective absorption of microwave energy by polar molecules, which are inert to the microwave dielectric loss. Among them, heterogeneous reactions18,19 facilitated by supported reagents on various mineral oxides have received special attention in recent years.

Silica gel supported sodium hydrogen sulfate (NaHSO4.SiO2), a non-toxic and inexpensive catalyst, has been used for one-pot conversion of ketones to amides18 and single-step synthesis of 4(3H)-quinazolinones.20 Owing to our interest in synthesizing fascinating pharmacological and therapeutic important compounds under solid-state reactions,21,22 we report now to use silica gel supported sodium hydrogen sulphate (NaHSO4.SiO2), as a heterogeneous catalyst for the one-pot conversion of 3,3,-dimethyl-2,6-diaryl-piperidin-4-ones (1-5) to 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles (11-15) in dry media under microwave irradiation.

 

RESULTS AND DISCUSSION

The only classical method23 available for the synthesis of 1,2,3-selenadiazoles is the conversion of semicarbazones of respective ketones by selenium dioxide in acetic acid medium. There are some problems associated with above synthesis, such as severe conditions, low to moderate yields for the reaction, difficulty in separating the products from the system, and serious environmental pollution. In the present procedure, treatment of 0.01 mole of 3,3-dimethyl-2,6-diaryl-piperidin-4-ones, 0.01 mole of semicarbazide and 0.01 mole of selenium dioxide along with a catalytic amount of NaHSO4.SiO2 afford the corresponding 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles (11-15) (Scheme 1) in high yields with shorter time period in dry media under MW irradiation than the classical method and the results are shown in Table 1. Also, the present dry media procedure eliminates the usage of glacial acetic acid23 solvent for the formation of respective 1,2,3-selenadiazoles. NaHSO4.SiO2 catalyst was shown to be one of the most efficient MW absorber with a very high specificity to MW heating. It was able to reach a temperature of 110 ℃ after 3 minutes of irradiation in a domestic oven (320 W). Mere 100 mg of NaHSO4.SiO2 catalyst to 0.01 moles of substrates is the most acceptable ratio in terms of efficiency and safety; a power level of 320 watts is the most suitable one.

Scheme 1.One-pot synthesis of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles.

Table 1.Reaction time and yields of compounds 11-15

The conversion of 3,3-dimethyl-2,6-diaryl-piperidin-4-ones (1-5) into 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles (11-15) by this method is believed to be followed via the 3,3-dimethyl-2,6-diaryl-piperidin-4-one semicarbazones derivative (6-10). In the first step, 3,3-dimethyl-2,6-diarylpiperidin-4-ones are converted to their respective semicarbazones and rapidly rearrange to give 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles in the second step. The attempt to isolate the respective semicarbazones from the reaction mixture is unsuccessful.

The formations of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles via the semicarbazones are confirmed by the same kind of reactions carried out using NaHSO4.SiO2 catalyst and 3,3-dimethyl-2,6-diarylpiperidin-4-one semicarbazones (6-10) and under microwave irradiation for 2-3 min. The products formed from the above two methods are found to be the same.

 

CONCLUSION

In conclusion, we have developed an efficient, environmentally friendly, one-pot microwave-assisted synthesis of 5,7-diaryl-4,4-dimethyl-4,5,6,7-tetrahy-dropyridino[3,4-d]-1,2,3-selenadiazoles in good yields under short reaction time.

General remarks

Performing TLC assessed the reactions and the purity of the products. All the reported melting points were taken in open capillaries and were uncorrected. IR spectra were recorded in KBr (pellet forms) on a Nicolet-Avatar-330 FT-IR spectrophotometer and note worthy absorption values (cm-1) alone are listed. 1H and 13C NMR spectra were recorded at 400 MHz and 100 MHz respectively on Bruker AMX 400 NMR spectrometer using CDCl3 as solvent. The ESI +ve MS spectra were recorded on a Bruker Daltonics LC-MS spectrometer. Satisfactory microanalysis was obtained on Carlo Erba 1106 CHN analyzer. A conventional (unmodified) domestic microwave oven equipped with a turntable (LG, MG-395 WA, 230V~50Hz, 760 W) was used for the irradiation.

Experimental procedure for the preparation of NaHSO4.SiO2: To a solution of 0.01 mole of NaHSO4.H2O in 10 mL of water in a 50 mL beaker containing a stir bar was added 4 g of SiO2. The mixture was stirred for 15 min. and then gently heated on a hot plate with intermittent swirling, until a free flowing white solid was obtained. The catalyst was further dried by placing the beaker in an oven maintained at 120 ℃ for 24 h prior to use.

By adopting the literature precedent24, 3,3-dimethyl-2,6-diarylpiperidin-4-ones (1-5) and its semicarbazones were prepared.

Typical procedure for the synthesis of 5,7-diphenyl-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles 11: A mixture containing 0.01 mole of 3,3-dimethyl-2,6-diphenylpiperidin-4-one, 0.01 mole of semicarbazide, and 0.01 mole of selenium dioxide and NaHSO4.SiO2 (100mg) was added in an alumina bath and mixed properly with the aid of glass rod (10s) and then irradiated in a microwave oven for 5 min. at 320W (monitored by TLC). After completion of the reaction, the reaction mixture was extracted with ethyl acetate (3×5 mL). The catalyst and other solid wastes were removed by filtration. The combined organic layer was washed with water three times and then dried over anhydrous MgSO4. The organic layer was concentrated in vacuo to furnish the products, which were purified by column chromatography using ethyl acetate: petroleum ether (bp 40:60) in the ratio 2:8 as eluent. Yield: 70%; m.p. 97-99 ℃; MS: m/z 369, M+.; Molecular formula: C19H19N3Se; Elemental analysis: Carbon 61.91found (61.96cal.); Hydrogen 5.17found (5.20cal.); Nitrogen 11.38found (11.41cal.); IR (KBr) (cm-1): 3306, 3065, 3033, 2969, 2927, 2880, 2798, 1585, 682, 765, 700; 1H NMR (δ ppm): 1.25 (s, 3H, CH3 at C-4), 1.70 (s, 3H, CH3 at C-4), 1.94 (s, 1H, H6); 4.80 (s, 1H, H5), 5.39 (s, 1H, H7), 7.22-7.60 (m, 10H, Harom); 13C NMR (δ ppm): 26.5 CH3 at C-4, 28.1 CH3 at C-4, 37.5 C-4, 69.5 C-5, 73.9 C-7, 140.4, 142.8 ipso-C, 159.1 C-8, 170.5 C-9, 126.9-128.8 -Carom.

The compounds 7-10 were synthesized similarly.

5,7-Bis(p-methylphenyl)-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles 12: Irradiation reaction time = 5 min.; Yield: 65%; m.p. 100-101 ℃; MS: m/z 397, M+.; Molecular formula: C21H23N3Se; Elemental analysis: Carbon 63.60found (63.63cal.); Hydrogen 5.81found (5.85cal.); Nitrogen 10.58found (10.60cal.); IR (KBr) (cm-1): 3300, 3022, 2965, 2923, 2854, 1580, 818,670; 1H NMR (δ ppm): 1.20 (s, 3H, CH3 at C-4), 1.71 (s, 3H, CH3 at C-4), 2.27 (s, 1H, H6); 2.35 (s, 6H, CH3 at Arom. ring), 4.83 (s, 1H, H5), 5.41 (s, 1H, H7), 7.14-7.28 (m, 8H, Harom); 13C NMR (δ ppm): 21.1 CH3 at Arom. ring, 26.8 CH3 at C-4, 28.1 CH3 at C-4, 37.5 C-4, 68.2 C-5, 73.5 C-7, 134.9, 137.2, 141.5, 142.6 ipso-C, 158.9 C-8, 170.5 C-9, 127.0-129.4 -Carom.

5,7-Bis(p-methoxylphenyl)-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles 13: Irradiation reaction time = 4 min.; Yield: 68%; m.p. 106-108 ℃; MS: m/z 429, M+.; Molecular formula: C21H23N3O2Se; Elemental analysis: Carbon 58.85found (58.88cal.); Hydrogen 5.37found (5.41cal.); Nitrogen 9.79found (9.81cal.); IR (KBr) (cm-1):3315, 2959, 2925, 2923, 1578, 831, 668; 1H NMR (δ ppm): 1.38 (s, 3H, CH3 at C-4), 1.54 (s, 3H, CH3 at C-4), 2.35 (s, 1H, H6); 3.81 (s, 6H, OCH3 at Arom. ring), 4.79 (s, 1H, H5), 5.34 (s, 1H, H7), 7.22-7.44 (m, 8H, Harom); 13C NMR (δ ppm): 24.5 CH3 at C-4, 25.6 CH3 at C-4, 37.7 C-4, 55.2, 55.5 -OCH3 at Arom. ring, 68.0 C-5, 73.2 C-7, 130.2, 131.9, 159.1, 159.7 ipso-C, 158.5 C-8, 170.5 C-9, 113.8-129.7 -Carom.

5,7-Bis(p-chlorophenyl)-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles 14: Irradiation reaction time = 4 min.; Yield: 70%; m.p. 110-112 ℃; MS: m/z 438, M+.; Molecular formula: C19H17Cl2N3Se; Elemental analysis: Carbon 52.13found (52.19cal.); Hydrogen 3.90found (3.92cal.); Nitrogen 9.57found (9.61cal.); IR (KBr) (cm-1): 3322, 3297, 2929, 2863, 1588, 834, 676; 1H NMR (δ ppm): 1.20 (s, 3H, CH3 at C-4), 1.72 (s, 3H, CH3 at C-4), 2.16 (s, 1H, H6), 4.49 (s, 1H, H5), 5.06 (s, 1H, H7), 7.22-7.48 (m, 8H, Harom); 13C NMR (δ ppm): 26.1 CH3 at C-4, 28.2 CH3 at C-4, 37.5 C-4, 68.8 C-5, 73.2 C-7, 133.4, 136.6, 137.2, 138.5 ipso-C, 158.5 C-8, 170.8 C-9, 128.1-130.7 -Carom.

5,7-Bis(p-fluorophenyl)-4,4-dimethyl-4,5,6,7-tetrahydropyridino[3,4-d]-1,2,3-selenadiazoles 15: Irradiation reaction time = 4 min.; Yield: 74%; m.p. 119-120 ℃; MS: m/z 405, M+.; Molecular formula: C19H17F2N3Se; Elemental analysis: Carbon 56.41found (56.44cal.); Hydrogen 4.21found (4.24cal.); Nitrogen 10.35found (10.39cal.); IR (KBr) (cm-1): 3320, 3293, 2924, 2859, 1579, 1201, 823, 671; 1H NMR (δ ppm): 1.23 (s, 3H, CH3 at C-4), 1.77 (s, 3H, CH3 at C-4), 2.19 (s, 1H, H6), 4.51 (s, 1H, H5), 5.09 (s, 1H, H7), 7.28-7.51 (m, 8H, Harom); 13C NMR (δ ppm): 26.7 CH3 at C-4, 28.4 CH3 at C-4, 37.9 C-4, 69.1 C-5, 73.5 C-7, 134.4, 137.1, 138.7, 139.5 ipso-C, 159.3 C-8, 171.3 C-9, 129.5-131.6 -Carom.

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