5
250 (100) [M]+, 208 (15), 117 (78), 91 (47). HRMS (ESI): calcd. for
C16H15N2O [M+H]+ 251.1184; found 251.1187.
9
10
Stanovnik, B.; Svete, J. Science of Synthesis 2002, 12, 15225.
Abbady, M. S.; Youssef, M. S. K. Med. Chem. Res. 2014, 23,
35583568.
3-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-5(4H)-one (3m). Yellow
solid (57 mg, 21%), m.p. 146-148 °C. 1H NMR (400.13 MHz,
CDCl3): δ = 3.83 (2 H, s), 7.42-7.46 (5 H, m), 7.70-7.73 (2 H, m),
7.95 (2 H, d, J = 7.7 Hz) ppm. 13C NMR (100.62 MHz, CDCl3): δ =
39.5, 119.1, 127.2, 128.9, 129.0, 129.2, 129.3, 136.7, 137.9, 153.5,
170.0 ppm. GC/MS (70 eV): m/z (%) = 270 (100) [M]+, 228 (13),
137 (45), 91 (53), 77 (51). HRMS (ESI): calcd. for C15H12ClN2O
[M+H]+ 271.0638; found 271.0636.
11
12
Tabei, K.; Kawashima, E.; Kato, T. Chem. Pharm. Bull. 1981, 29,
2449.
Wall, M.; Subasinghe, N.; Sui, Z.; Flores, C. PCT Int. Appl. (2014),
WO 2014028803A1, 2014.
Eller, G. A.; Holzer, W. Molbank 2006, 2006, M464.
13
14
a) Troisi, L.; De Vitis, L.; Granito, C.; Pilati, T.; Pindinelli, E.
Tetrahedron 2004, 60, 6895–6900. b) Troisi, L.; Ronzini, L.;
Granito, C.; Pindinelli, E.; Troisi, A.; Pilati, T. Tetrahedron 2006,
62, 12064–12070. c) Troisi, L.; Granito, C.; Pindinelli, E.
Tetrahedron 2008, 64, 11632–11640. d) Perrone, S.; Cannazza, G.;
Caroli, A.; Salomone, A.; Troisi, L. Tetrahedron 2014, 70,
69386943. e) Tommasi, S.; Perrone, S.; Rosato, F.; Salomone, A.;
Troisi, L. Synthesis 2012, 44, 423430. f) Troisi, L.; Granito, C.;
Rosato, F.; Videtta, V. Tetrahedron Lett. 2010, 51, 371–373. g)
Perrone, S; Bona, F.; Troisi, L. Tetrahedron 2011, 67, 73867391.
a) Perrone, S.; Caroli, A.; Cannazza, G.; Granito, C.; Salomone, A.;
Troisi L. Tetrahedron Lett. 2015, 56, 27732776. b) Perrone, S.;
Capua, M.; Salomone, A.; Troisi, L. J. Org. Chem. 2015, 80,
81898197. c) Perrone, S.; Salomone, A.; Caroli, A.; Falcicchio, A.;
Citti, C.; Cannazza, G.; Troisi, L. Eur. J. Org. Chem. 2014, 5932–
5938. d) Perrone, S.; Capua, M.; Cannazza, G.; Salomone, A.;
Troisi, L. Thetrahedron Lett. 2016, 57, 14211424.
For some recent synthesis of pyrimidine-2,4-dione derivatives from
-ketoesters and ureas see: a) Aware, V; Gaikwad, N.; Chavan, S.;
Manohar, S.; Bose, J.; Khanna, S.; B-Rao, C.; Dixit, N.; Singh, K.
S.; Damre, A.; Sharma, R.; Patil, S.; Roychowdhury, A. Eur. J. Med.
Chem. 2015, 92, 246256. b) Zhu, W.; Sun, C.; Xu, S.; Wu, C.; Wu,
J.; Xu, M.; Zhao, H.; Chen, L.; Zeng, W.; Zheng, P. Bioorg. Med.
Chem. 2014, 22, 6746–6754.
5-(tert-Butyl)-1-(4-chlorophenyl)-1H-pyrazol-3(2H)-one (4a). Pale
1
yellow oil (30 mg, 12%). H NMR (400.13 MHz, CDCl3): δ = 1.21
(9 H, s), 5.53 (1 H, s), 7.31 (2 H, d, J = 7.5 Hz), 7.40 (2 H, d, J = 7.5
Hz) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 30.6, 40.8, 90.6,
128.2, 129.1, 130.2, 135.1, 161.4, 177.6 ppm. GC/MS (70 eV): m/z
(%) = 250 (51) [M]+, 235 (100), 200 (33), 111 (25). HRMS (ESI):
calcd. for C13H16ClN2O [M+H]+ 251.0951; found 251.0949.
15
16
5-(2-Bromophenyl)-1-phenyl-1H-pyrazol-3(2H)-one (4h). Yellow oil
1
(141 mg, 45%). H NMR (400.13 MHz, CDCl3): δ = 5.94 (1 H, s),
7.18-7.30 (8 H, m), 7.57 (1 H, d, J = 7.8 Hz) ppm. 13C NMR (100.62
MHz, CDCl3): δ = 95.7, 124.0, 126.9, 127.2, 128.9, 130.5, 132.1,
133.1, 138.9, 142.7, 162.5 ppm. GC/MS (70 eV): m/z (%) = 314 (62)
[M]+, 235 (34), 207 (100), 180 (30), 103 (23), 77 (51). HRMS (ESI):
calcd. for C15H11BrN2O [M+H]+ 315.0133; found 315.0135.
17
18
19
20
21
22
Mojtahedi, M. M.; Javdpour, M.; Abaee, M. S. Ultrason. Sonochem.
2008, 15, 828832.
Han, X.; Yao, W.; Wang, T.; Ren, Y.; Yan, T. Z.; Kwiatkowski, J.;
Lu, Y. Angew. Chem. Int. Ed. 2014, 53, 56435647.
Liu, Y.; He, G.; Chen, K.; Jin, Y.; Li, Y.; Zhu, H. Eu. J. Org. Chem.
2011, 5323-5330.
Kimata, A.; Nakagawa, H.; Ohyama, R.; Fukuuchi, T.; Ohta, S.;
Suzuki, T.; Miyata, N. J. Med. Chem. 2007, 50, 50535056.
Salanouve, E.; Guillou, S.; Bizouarne, M.; Bonhomme, F. J.; Janin,
Y. L. Tetrahedron 2012, 68, 31653171.
General procedure for the synthesis of pyrazolones 3a-m and 4a-i: a
solution containing the α-chloroketone 1 (2.0 mmol or 3.0 mmol in
the case of aromatic ketones), hydrazine 2 (1.0 mmol), Pd(AcO)2 (11
mg, 5 mol%), PPh3 (52 mg, 0.20 mmol), and NEt3 (0.5 mL, 4.0
mmol) in anhydrous THF (15 mL) was placed in a 45 mL autoclave.
The autoclave was purged, pressurized with CO (27 atm), and then
heated at 110 °C under magnetic stirring, for 10 h. After this time,
the solution was cooled to room temperature, and the solvent was
removed under reduced pressure. The crude reaction mixture was
then purified by chromatography on silica gel [petroleum
ether/AcOEt (90:10 to 30:70)] to obtain the corresponding
pyrazolones derivatives 3a-m and 4a-i as pure compounds.
Compounds 3a, 3b, 3d, 3e, 3f, 3h, 3i, 3j and 4b, 4c, 4d, 4g, 4i are
known and their characterization data are in agreement with those
reported in the literature (see references 1721 cited in Table 2).
Characterization data for compounds 3c,g,m and 4a,h are unknown
and given below:
3-(tert-Butyl)-1-(4-chlorophenyl)-1H-pyrazol-5(4H)-one (3c). Pale
1
yellow oil (138 mg, 55%). H NMR (400.13 MHz, CDCl3): δ = 1.27
(9 H, s), 3.45 (2 H, s), 7.47 (2 H, d, J = 7.5 Hz), 7.59 (2 H, d, J = 7.5
Hz) ppm. 13C NMR (100.62 MHz, CDCl3): δ = 28.1, 37.4, 38.9,
128.4, 129.0, 132.9, 136.2, 164.5, 171.1 ppm. GC/MS (70 eV): m/z
(%) = 250 (100) [M]+, 235 (95), 207 (10), 111 (48), 83 (61). HRMS
(ESI): calcd. for C13H16ClN2O [M+H]+ 251.0951; found 251.0953.
1-Phenyl-3-(p-tolyl)-1H-pyrazol-5(4H)-one (3g). Brown solid (138
1
mg, 55%), m.p. 150-152 °C. H NMR (400.13 MHz, CDCl3): δ =
2.39 (3 H, s), 3.76 (2 H, s), 7.18-7.24 (3 H, m), 7.40-7.43 (2 H, m),
7.63 (2 H, d, J = 7.3 Hz), 7.97 (2 H, m) ppm. 13C NMR (100.62
MHz, CDCl3): δ = 21.5, 39.6, 118.9, 125.1, 125.9, 128.1, 128.8,
129.5, 138.1, 141.1, 154.7, 170.2 ppm. GC/MS (70 eV): m/z (%) =