Paper
NJC
doublet), t (triplet) and m (multiplet). High-resolution mass 140.42, 137.38, 129.07, 126.66, 101.97, 60.02, 54.95, 21.00, 17.79,
spectroscopy was carried out using an Agilent ESI-TOF mass 14.03. HRMS (ESI): m/z calcd for C15H18N2O2S: 290.1098; found
spectrometer. X-ray analysis was carried out using an Oxford 291.1172 [M + H].
Diffraction Xcalibur four-circle diffractometer equipped with a
Ethyl-4-(4-hydroxy-3,5-ditertbutylphenyl)-6-methyl-2-oxo-1,2,3,4-
Eos CCD detector using graphite mono-chromatized Mo-Ka radia- tetrahydropyrimidine-5-carboxylate (4e). White crystalline solid;
tion (l = 0.71073 Å). For the single X-ray crystallography, crystals of M.P. = 210–212 1C. 1H NMR (400 MHz, CDCl3) d ppm: 9.48
compound 4k and 6j were grown in ethanol solvent at room (s, 1H), 7.36 (s, 2H), 5.10 (s, 1H), 3.84 (brs, 3H), 2.74 (q, 2H),
temperature by slow evaporation of solution growth method.
1.41 (s, 18H), 0.95 (t, J1 = 8.33 Hz, J2 = 8.46 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d ppm: 191.93, 190.64, 159.83, 137.51, 127.97,
127.80, 127.32, 126.52, 53.75, 53.56, 34.14, 31.12, 30.13, 29.17.
HRMS (ESI): m/z calcd for C22H32N2O4: 388.2362; found 389.2421
3.2 General procedure for the synthesis of 1,2,3,4-tetrahydropyri-
midine-2-thione/ones using [Et3NH][HSO4] (4a–4o)
To an equivalent mixture of thiourea/urea (1a/1b) (1 mmol), [M + H].
ethyl acetoacetate (2) and substituted benzaldehyde (3), qua-
Ethyl-4-(4-hydroxy-3,5-ditertbutylphenyl)-6-methyl-2-thioxo-
ternary ammonium ionic liquid [Et3NH][HSO4] (loading of 1,2,3,4-tetrahydropyrimidine-5-carboxylate (4f). White crystal-
15 mol%) was added. The reaction mixture was stirred at room line solid; M.P. = 200–202 1C. 1H NMR (400 MHz, CDCl3) d
temperature for about 30–45 min. The progress of the reaction ppm: 9.28 (s, 1H), 7.15 (s, 2H), 4.88 (s, 1H), 3.98 (brs, 3H), 2.51
was monitored by TLC (eluent = n-hexane/EtoAc = 9/1). After (q, 2H), 0.93 (s, 18H), 0.75 (t, J1 = 8.23 Hz, J2 = 8.13 Hz, 3H); 13
C
completion of the reaction, the organic layer was extracted NMR (100 MHz, CDCl3) d ppm: 191.69, 184.38, 176.86, 160.08,
using ethyl acetate, which was further dried over Na2SO4 and 137.53, 128.24, 127.32, 110.49, 53.67, 45.49, 34.42, 29.97, 12.88,
evaporated under vacuum. The crude product was purified by 8.54. HRMS (ESI): m/z calcd for C22H32N2O3S: 404.2134; found
recrystallization from ethanol or by column chromatography 405.2213 [M + H].
wherever required to obtain the pure desired 1,2,3,4-
Ethyl-4-(3-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyri-
tetrahydropyrimidine-2-thione/ones (4a–4o) products. Finally, midine-5-carboxylate (4g). White crystalline solid; M.P. = 209–
the product was confirmed by several known techniques such 210 1C. 1H NMR (400 MHz, CDCl3) d ppm: 8.94 (s, 1H), 7.08 (dd,
as 1H NMR, 13C NMR, High Resolution Mass Spectroscopy (HR- J = 12.2, 7.6 Hz, 1H), 6.94 (d, J = 7.7 Hz, 1H), 6.84 (d, J = 11.3 Hz,
MS) and single-crystal X-ray diffraction analysis.
1H), 6.74 (t, J = 8.4 Hz, 1H), 5.13 (s, 1H), 3.86 (q, 2H), 2.14 (s, 3H),
Ethyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5- 0,97 (t, 3H); 13C NMR (100 MHz, CDCl3) d ppm: 170.62, 165.67,
carboxylate (4a). White crystalline solid; M.P. = 200–202 1C. (206– 158.09, 153.26, 152.18, 134.80, 127.18, 118.48, 118.26, 104.57,
207 1C).50 1H NMR (400 MHz, CDCl3) d ppm: 8.56 (s, 1H), 6.94– 64.53, 59.26, 23.15, 19.05.
6.79 (m, 5H), 6.26 (brs, 1H), 3.56 (q, J = 7.2 Hz, 2H), 1.85 (s, 3H),
Ethyl-4-(3-fluorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-
0.68 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d ppm: 165.63, pyrimidine-5-carboxylate (4h). White crystalline solid; M.P. =
152.98, 147.65, 144.56, 128.13, 127.16, 126.42, 99.95, 59.33, 54.64, 213–214 1C. 1H NMR (400 MHz, CDCl3) d ppm: 9.88 (s, 1H), 9.26
13.95, 8.40. HRMS (ESI): m/z calcd for C14H16N2O3: 260.1177; (s, 1H), 7.12 (dd, J = 13.5, 7.84 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H),
found 261.1247 [ M + H].
6.78–6.84 (m, 2H), 5.13 (s, 1H), 3.91 (q, 2H), 2.17 (s, 3H), 1.00
Ethyl-6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine- (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d ppm 170.62,
5-carboxylate (4b). White crystalline solid; M.P. = 200–201 1C 168.71, 158.09, 153.26, 152.18, 134.87, 127.18, 119.14, 118.93,
(208–209 1C).50 1H NMR (400 MHz, CDCl3) d ppm: 9.27 (s, 1H), 104.57, 64.53, 59.26, 23.15, 19.05. HRMS (ESI): m/z calcd for
8.64 (s, 1H), 7.11–6.97 (m, 5 H), 5.15 (s, 1H), 3.88 (q, 2H), 2.16 C14H15FN2O2S: 294.0838; found 295.0885 [M + H].
(s, 3H), 0.97 (t, J1 = 8.01 Hz, J2 = 7.98 Hz, 3H); 13C NMR (100 MHz,
Ethyl-4-(4-chlorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-
CDCl3) d ppm: 174.63, 165.62, 144.28, 143.34, 129.04, 127.36, pyrimidine-5-carboxylate (4i). White crystalline solid; M.P. =
126.35, 101.95, 60.02, 55.40, 18.36, 14.63. HRMS (ESI): m/z calcd 202–204 1C (215–216 1C).50 1H NMR (400 MHz, CDCl3) d ppm:
for C14H16N2O2S: 276.0928; found 277.1007 [M + H].
9.26 (s, 1H), 7.78 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.24 (s, 1H),
Ethyl-6-methyl-2-oxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine- 5.13 (s, 1H), 3.97 (q, J = 7.1 Hz, 2H), 2.24 (s, 3H), 1.08 (t, J =
5-carboxylate (4c). White crystalline solid; M.P. = 204–206 1C 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) d ppm: 163.10, 149.93,
(206–207 1C).21 1H NMR (400 MHz, CDCl3) d ppm: 9.034 (s, 1H), 146.62, 141.69, 129.77, 126.24, 126.01, 96.74, 57.13, 51.38,
7.19 (d, J = 8.12 Hz, 2H), 7.08 (d, J = 8.31 Hz, 2H), 5.26 (s, 1H), 15.78, 12.01. HRMS (ESI): m/z calcd for C14H15ClN2O3:
4.03 (q, 2H), 2.93 (s, 1H), 2.30 (s, 6H), 1.17 (t, J1 = 8.12 Hz, J2 = 294.0775; found 295.0838 [M + H].
8.32 Hz, 3H); 13C NMR (100 MHz, CDCl3) d ppm: 170.78, 158.24,
152.49, 146.72, 141.72, 133.86, 131.41, 105.29, 64.42, 59.42, pyrimidine-5-carboxylate (4j). White crystalline solid; M.P. = 208–
25.92, 23.13, 19.07.
210 1C (180–181 1C).50 1H NMR (400 MHz, CDCl3) d ppm: 9.50
Ethyl-4-(4-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-
Ethyl-6-methyl-2-thioxo-4-(p-tolyl)-1,2,3,4-tetrahydropyrimidine- (s, 1H), 8.86 (s, 1H), 7.05 (d, J = 6 Hz, 2H), 6.90 (d, J = 7 Hz, 2H),
5-carboxylate (4d). White crystalline solid; M.P. = 207–208 1C. 4.93 (s, 1H), 3.96 (q, 2H), 1.97 (s, 3H), 0.93 (t, J1 = 8.01 Hz, J2 =
1H NMR (400 MHz, CDCl3) d ppm: 9.18 (s, 1H), 8.52 (s, 1H), 8.21 Hz, 3H); 13C NMR (100 MHz, CDCl3) d ppm: 194.51, 167.71,
6.92 (d, J = 8 Hz, 2H), 6.82 (d, J = 8 Hz, 2H), 5.02 (s, 1H), 3.79 167.17, 130.97, 130.62, 128.96, 128.23, 101.13, 61.59, 54.23,
(q, 2H), 2.06 (s, 3H), 2.03 (s, 3H), 0.89 (t, J1 = 8.12 Hz, J2 = 8.01 Hz, 26.30, 13.98. HRMS (ESI): m/z calcd for C14H15ClN2O2S:
3H); 13C NMR (100 MHz, CDCl3) d ppm: 174.50, 165.60, 144.10, 310.0535; found 311.0615 [M + H].
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New J. Chem., 2021, 45, 6724–6738
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