Chemistry
All solvents and inorganic reagents were from commercial sources and used without purification unless otherwise noted. Reactions were carried out in oven-dried round-bottom flask. Melting points were determined on a X-4 digital display micro-melting point tester (Beijing Tec Instrument Co., Ltd.) apparatus and were uncorrected. Proton nuclear magnetic resonance (1H NMR) spectra and carbon nuclear magnetic resonance (13C NMR) spectra were recorded on Bruker 600MHz spectrometer (600 MHz and 150 MHz). Chemical shifts for protons are reported in parts per million downfield from tetramethylsilane and are referenced to residual protium in the NMR solvent (DMSO-d6: δ 2.5). Chemical shifts for carbon are reported in parts per million downfield from tetramethylsilane and are referenced to the carbon resonances of the solvent (DMSO-d6: δ 39.5). Due to improper storage of DMSO-d6 in the laboratory, it contains a certain amount of water. See its 1H NMR for details (δ 3.33 ± 0.10 S). Data are represented as follows: chemical shift, integration, multiplicity (br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants in Hertz (Hz). All highresolution mass spectra were obtained on a Watersq-tof mass spectrometer. Analytical TLC was performed using EM separations percolated silica gel 0.2 mm layer UV 254 fluorescent sheets.
Synthesis of 5-arylselanyluracil (3a-3p, 5a-b, 7a-c, 9a, 11a)
Procedure A: Uracil (1a) (0.53 mmol, 1.0 eq), Se powder (1.325 mmol, 2.5 eq), Cs2CO3 (1.6 mmol, 3eq) and phenylhydrazine hydrochloride derivativewere (1.6 mmol, 3eq) added to dimethylsulfoxide (1.5 mL) in around-bottom flask. After stirring at 100 ° C for 6-10 h, the mixture was cooled to room temperature. Adjust the acidity with dilute hydrochloric acid, add 15ml of H2O, stir at room temperature for 10-20min, filter, and purify the solid crude product on silica gel column chromatography to obtain the required products 3a-p and 11a.
Procedure B: Pyrimidine (4, 6, 8, 0.53 mmol, 1.0 eq), Se powder (1.34 mmol, 2.5 eq), Cs2CO3 (1.6 mmol, 3eq) and phenylhydrazine hydrochloride derivative (1.6 mmol, 3eq) were added to dimethylsulfoxide (1.5 mL) in around-bottom flask. After stirring at 100℃ for 8-48 h, the mixture was cooled to room temperature and evaporated to dryness under reduced pressure. The crude product was puried on a silica gel column chromatography to give the desired product 5a-b, 7a–c and 9a.
Characterization Data for All Products
5. (phenylselanyl)pyrimidine-2,4(1H,3H)-dione (3a)[5, 17]
Off white solid (84%). M.p: 255-256 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.35 (s, 1H), 11.24 (s, 1H), 7.77 (s, 1H), 7.38 – 7.34 (m, 2H), 7.28 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H).
5-(o-tolylselanyl)pyrimidine-2,4(1H,3H)-dione(3b) [17]
Off white solid (70%). M.p: 272-274 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.39 (s, 1H), 11.26 (s, 1H), 7.71 (s, 1H), 7.21 (d, J = 7.3 Hz, 1H), 7.14 (dd, J = 11.1, 4.1 Hz, 2H), 7.09 (t, J = 7.4 Hz, 1H), 2.32 (s, 3H).
5-(m-tolylselanyl)pyrimidine-2,4(1H,3H)-dione (3c)
Light yellow solid (75%). M.p: 298-299 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.36 (s, 1H), 11.23 (s, 1H), 7.74 (s, 1H), 7.20 – 7.13 (m, 3H), 7.05 (d, J = 7.1 Hz, 1H), 2.26 (s, 3H). 13C NMR (151 MHz, DMSO-d6) δ 162.9, 151.8, 148.3, 139.1, 131.3, 130.8, 129.6, 127.9, 127.5, 100.2, 21.3. HRMS [ESI]: calculated for: C11H9N2O2Se[M-H]:280.9835, found 280.9854.
5-(p-tolylselanyl)pyrimidine-2,4(1H,3H)-dione(3d) [5,17]
Off white solid (78%). M.p: 280-282°C. 1H NMR (600 MHz, DMSO-d6) δ 11.34 (s, 1H), 11.17 (s, 1H), 7.64 (s, 1H), 7.28 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 2.26 (s, 3H).
5-((2-fluorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3e)
Light yellow solid (78%). M.p: 236-238°C. 1H NMR (600 MHz, DMSO-d6) δ 11.39 (d, J = 33.4 Hz, 2H), 7.89 (s, 1H), 7.28 (td, J = 7.3, 1.5 Hz, 1H), 7.20 (dt, J = 7.4, 4.9 Hz, 2H), 7.14 – 7.09 (m, 1H). 13C NMR (151 MHz, DMSO-d6) δ 162.9, 151.9, 150.0, 134.5, 134.2, 131.2, 128.9, 128.2, 126.7, 99.0. HRMS [ESI]: calculated for: C10H8FN2O2Se[M+H]:286.9730, found 286.9727.
5-((3-fluorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione(3f) [17]
Light yellow solid (78%). M.p: 259-261°C. 1H NMR (600 MHz, DMSO-d6) δ 11.39 (s, 1H), 11.33 (s, 1H), 7.91 (s, 1H), 7.34 – 7.28 (m, 1H), 7.17 (dd, J = 11.1, 4.8 Hz, 2H), 7.04 (td, J = 8.8, 2.2 Hz, 1H).
5-((3-chlorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione(3g)
Yellowish brown solid (96%). M.p: 226-228°C. 1H NMR (600 MHz, DMSO-d6) δ 11.38 (d, J = 19.5 Hz, 2H), 7.93 (s, 1H), 7.38 (s, 1H), 7.28 (ddd, J = 7.4, 4.0, 2.4 Hz, 3H). 13C NMR (151 MHz, DMSO-d6) δ 162.9, 151.9, 149.9, 134.5, 134.2, 131.2, 128.9, 128.2, 126.7, 99.0. HRMS [ESI]: calculated for: C10H7ClN2O2NaSe[M+Na]: 324.9259, found 324.9248.
5-((4-chlorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3h) [17]
Light brown solid (76%). M.p: 278-280 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.39 (s, 2H), 7.87 (s, 1H), 7.36 (d, J = 8.6 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H).
5-((4-bromophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3i) [17]
White solid (93%). M.p: 281-283 °C. 1H NMR (600 MHz, DMSO) δ 11.35 (d, J = 44.9 Hz, 2H), 7.88 (s, 1H), 7.45 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H).
5-((2,4-difluorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3j)
Off white solid (60%). M.p: 289-291 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.37 (d, J = 46.0 Hz, 2H), 7.85 (s, 1H), 7.34 – 7.27 (m, 2H), 7.04 (td, J = 8.6, 2.5 Hz, 1H). 13C NMR (151 MHz, DMSO) δ 162.8, 151.8, 149.4, 133.3, 113.2, 113.1, 104.8, 104.6, 104.5, 97.7. HRMS [ESI] calculated for: C10H5F2N2O2Se[M-H]:302.9563, found 302.9515.
5-((2,4-dichlorophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione(3k)
Off white solid (78%). More than 300 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.48 (s, 2H), 8.02 (s, 1H), 7.61 (d, J = 2.2 Hz, 1H), 7.29 (dd, J = 8.5, 2.2 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H). 13C NMR (151 MHz, DMSO-d6) δ 162.8, 151.9, 151.4, 132.2, 132.1, 131.4, 130.6, 129.0, 128.4, 97.3. HRMS [ESI] calculated for: C10H5Cl2N2O2Se[M-H]: 334.8901, found 334.8920.
5-((4-nitrophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione(3l)
Yellowish brown solid (44%). M.p: 265-267 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.39 (s, 1H), 11.31 (s, 1H), 7.87 (s, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H). 13C NMR (151 MHz, DMSO-d6) δ 162.7, 151.9, 151.1, 146.0, 144.1, 129.0, 124.2, 97.9. HRMS [ESI]: calculated for: C10H7N3O4NaSe[M+Na]: 335.9503, found 335.9568.
5-((3-nitrophenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3m)
Yellow solid (33%). M.p: 259-261 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.46 (s, 2H), 8.13 (t, J = 1.9 Hz, 1H), 8.06 – 8.03 (m, 2H), 7.78 (d, J = 8.3 Hz, 1H), 7.55 (t, J = 8.0 Hz, 1H). 13C NMR (151 MHz, DMSO-d6) δ 162.9, 151.9, 150.5, 148.6, 135.9, 134.9, 130.8, 123.7, 121.6, 98.6. HRMS [ESI]: calculated for: C10H6N3O4Se[M-H]: 311.9529, found 311.9564.
4-((2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl) selanyl) benzonitrile (3n) [5]
White solid (89%). M.p: 284-286 °C. 1H NMR (600 MHz, DMSO-d6) δ 8.01 (s, 1H), 7.67 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H).
5-((4-methoxyphenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3o) [17]
Brown solid (75%). M.p: 275-277 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.33 (s, 1H), 11.10 (s, 1H), 7.46 (s, 1H), 7.43 – 7.39 (m, 2H), 6.90 (d, J = 8.7 Hz, 2H), 3.74 (s, 3H).
5-((3-chloro-4-methylphenyl)selanyl)pyrimidine-2,4(1H,3H)-dione (3p)
Brown solid (76%). M.p: 250-252 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.40 (s, 1H), 11.31 (s, 1H), 7.86 (s, 1H), 7.39 (s, 1H), 7.27 – 7.22 (m, 2H), 2.27 (s, 3H). 13C NMR (151 MHz, DMSO) δ 162.9, 151.8, 149.0, 134.3, 134.3, 132.2, 130.4, 130.1, 129.2, 99.8, 19.6. HRMS [ESI]: calculated for: C11H10ClN2O2Se[M+H]: 316.9591, found 316.9544.
4-amino-5-(phenylselanyl)pyrimidin-2(1H)-one (5a)
White solid (62%). M.p: 250-252 °C. 1H NMR (600 MHz, DMSO-d6) δ 10.94 (s, 1H), 7.88 (s, 1H), 7.55 (s, 1H), 7.34 (d, J = 7.3 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 6.63 (s, 1H). 13C NMR (101 MHz, DMSO-d6) δ 166.3, 156.6, 152.37, 132.0, 129.8, 129.5, 127.1, 90.0. HRMS [ESI]: calculated for: C10H8N3OSe[M-H]: 265.9838, found 265.9879.
4-amino-5-(p-tolylselanyl)pyrimidin-2(1H)-one (5b)
White solid (38%). More than 300 °C. 1H NMR (600 MHz, DMSO-d6) δ 10.90 (s, 1H), 7.85 (s, 1H), 7.54 (s, 1H), 7.27 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.58 (s, 1H), 2.25 (s, 3H). 13C NMR (151 MHz, DMSO-d6) δ 166.4, 156.6, 151.7, 136.7, 130.5, 130.2, 128.0, 91.7, 21.0. HRMS [ESI]: calculated for: C11H11N3ONaSe[M+Na]:303.9965, found 303.9950.
2-amino-5-(phenylselanyl)pyrimidin-4(1H)-one (7a)
White solid (69%). M.p: 229-231 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.26 (s, 1H), 7.92 (s, 1H), 7.29 (d, J = 7.5 Hz, 2H), 7.25 (t, J = 7.5 Hz, 2H), 7.18 (t, J = 7.1 Hz, 1H), 6.94 (s, 2H). 13C NMR (151 MHz, DMSO-d6) δ 164.5, 161.5, 157.9, 133.0, 129.6, 128.5, 126.5, 101.6. HRMS [ESI]: calculated for: C10H8N3OSe[M-H]:265.9838, found 265.9855.
2-amino-5-((4-methoxyphenyl)selanyl) pyrimidin-4(1H)-one(7b)
White solid (70%). M.p: 264-266 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.14 (s, 1H), 7.76 (s, 1H), 7.33 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 6.78 (s, 2H), 3.73 (s, 3H). 13C NMR (151 MHz, DMSO-d6) δ 162.2, 161.3, 159.0, 157.4, 133.3, 121.6, 115.4, 103.6, 55.6. HRMS [ESI]: calculated for: C11H10N3O2Se[M-H]:295.9944, found 295.9971.
2-amino-5-((3-chlorophenyl)selanyl)pyrimidin-4(1H)-one (7c)
White solid (67%). M.p: 225-227 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.26 (s, 1H), 8.00 (s, 1H), 7.27 – 7.21 (m, 4H), 6.98 (s, 2H). 13C NMR (151 MHz, DMSO-d6) δ 165.2, 161.4, 158.2, 135.8, 134.1, 131.1, 128.3, 127.7, 126.2, 100.6. HRMS [ESI]: calculated for: C10H7ClN3O2Se[M-H]: 299.9448, found 299.9473.
6-amino-5-(phenylselanyl)pyrimidine-2,4(1H,3H)-dione (9a) [26]
White solid (66%). More than 300°C. 1H NMR (600 MHz, DMSO-d6) δ 10.57 (s, 1H), 10.41 (s, 1H), 7.26 – 7.20 (m, 4H), 7.17 – 7.12 (m, 1H), 6.50 (s, 2H).
1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-(phenylselanyl) pyrimidine-2,4(1H,3H)-dione (11a)[5]
Grey solid (70%). M.p: 208-210 °C. 1H NMR (600 MHz, DMSO-d6) δ 11.64 (s, 1H), 8.45 (s, 1H), 7.37 – 7.33 (m, 2H), 7.28 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.3 Hz, 1H), 5.78 (d, J = 4.7 Hz, 1H), 4.06 (t, J = 4.8 Hz, 1H), 3.96 (t, J = 4.8 Hz, 1H), 3.89 – 3.85 (m, 1H), 3.62 (dd, J = 12.0, 2.9 Hz, 1H), 3.51 (dd, J = 12.0, 2.8 Hz, 1H).