Chemistry of Heterocyclic Compounds 2017, 53(12), 1294–1301
mp 170–171°С. IR spectrum, ν, cm−1: 3280 (OH), 1658
room temperature. The obtained precipitate was filtered
off, washed with cold water, refluxed in CHCl3 (2 ml) in
order to remove impurities, cooled, and filtered. The
products were isolated as white crystals that noticeably
sublimated upon heating.
1
(CO), 1618, 1601, 1509. Н NMR spectrum (400 MHz,
DMSO-d6), δ, ppm (J, Hz): 3.10 (1H, d, J = 18.1) and 3.34
(1H, dd, J = 18.0, J = 1.6, 5-СН2); 4.58 (2H, s, NH2); 6.43
(1H, s, 3-CН); 7.28 (2H, t, J = 8.9, JHF = 8.9, H Ar); 7.40
(1H, s, OH); 7.76 (2H, dd, J = 8.9, JHF = 5.4, H Ar). 1Н NMR
spectrum (500 MHz, CDCl3), δ, ppm (J, Hz): 3.18 (1H, d,
J = 18.4) and 3.40 (1H, d, J = 18.4, 5-СН2); 4.07 (2H, s,
NH2); 5.26 (1H, s, OH); 6.30 (1H, d, J = 2.4, 3-CН); 7.13
(2H, t, J = 8.6, JHF = 8.6, H Ar); 7.49 (2H, dd, J = 8.8,
JHF = 5.2, H Ar). 19F NMR spectrum (471 MHz, CDCl3),
δ, ppm (J, Hz): 52.0 (tt, JHF = 8.4, JHF = 5.2, F); 79.9 (d,
JHF = 1.0, CF3). 13С NMR spectrum (126 MHz, CDCl3),
δ, ppm (J, Hz): 33.9 (C-5); 84.2 (q, 2JCF = 30.4, С-6); 116.2
1,6-Dihydroxy-4-phenyl-6-(trifluoromethyl)-5,6-dihydro-
pyridin-2(1H)-one (7e). Yield 46%, mp 188–189°С.
IR spectrum, ν, cm−1: 3266 (ОН), 1689 (CO), 1626.
1Н NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz):
3.15 (1H, d, J = 18.0) and 3.43 (1H, dd, J = 18.0; J = 2.1,
5-СН2); 6.38 (1H, d, J = 2.1, 3-CH); 7.43–7.47 (3H, m,
H Ph); 7.66–7.70 (2H, m, H Ph); 7.75 (1H, s, OH); 9.66
(1H, s, ОН). 19F NMR spectrum (376 MHz, DMSO-d6),
δ, ppm: 85.4 (s, CF3). 13C NMR spectrum (126 MHz,
DMSO-d6) δ, ppm (J, Hz): 35.1 (C-5); 86.9 (q, 2JCF = 29.5,
2
(d, JCF = 21.9, С-3',5' Ar); 117.1 (C-3); 124.1 (q,
3
1
1JCF = 291.8, CF3); 127.9 (d, JCF = 8.5, C-2',6' Ar); 132.3
C-6); 116.8 (C-3); 123.4 (q, JCF = 288.9, CF3); 126.2 (2C
(d, 4JCF = 3.4, C-1' Ar); 144.6 (C-4); 164.0 (d, 1JCF = 251.7,
C-4' Ar); 164.2 (CO). Found, %: C 49.53; H 3.60; N 9.67.
C12H10F4N2O2. Calculated, %: C 49.66; H 3.47; N 9.65.
1-Amino-4-(4-chlorophenyl)-6-hydroxy-6-(trifluoro-
methyl)-5,6-dihydropyridin-2(1H)-one (7c). Yield 72%,
mp 202–203°С. IR spectrum, ν, cm−1: 3281 (OH), 1655
(CO), 1614, 1593. 1Н NMR spectrum (400 MHz, DMSO-d6),
δ, ppm (J, Hz): 3.09 (1H, d, J = 18.2) and 3.34 (1H, dd,
J = 18.2, J = 1.6, 5-СН2); 4.59 (2H, s, NH2); 6.47 (1H, d,
J = 0.9, 3-CH); 7.42 (1H, s, OH); 7.50 (2H, d, J = 8.7, H Ar);
Ph); 128.8 (2C Ph); 130.0 (C Ph); 136.0 (C Ph); 145.3
(C-4); 164.4 (CO). Found, %: C 52.50; H 3.69; N 5.06.
C12H10F3NO3. Calculated, %: C 52.75; H 3.69; N 5.13.
4-(4-Fluorophenyl)-1,6-dihydroxy-6-(trifluoromethyl)-
5,6-dihydropyridin-2(1H)-one (7f). Yield 37%, mp 183–
185°С. IR spectrum, ν, cm−1: 3255 (ОН), 1680 (CO), 1625,
1
1597. Н NMR spectrum (400 MHz, DMSO-d6), δ, ppm
(J, Hz): 3.13 (1H, d, J = 18.1) and 3.43 (1H, dd, J = 18.1,
J = 1.7, 5-СН2); 6.37 (1H, d, J = 1.8, 3-CH); 7.28 (2H, t,
J = 8.8, JHF = 8.8, H Ar); 7.75 (1H, s, OH); 7.75 (2H, dd,
J = 8.8, JHF = 5.5, H Ar); 9.67 (1H, s, ОН). 19F NMR spectrum
(376 MHz, DMSO-d6), δ, ppm (J, Hz): 51.4 (tt, JHF = 9.0,
JHF = 5.5, F); 85.4 (s, CF3). Found, %: C 49.48; H 3.01;
N 4.75. C12H9F4NO3. Calculated, %: C 49.49; H 3.12; N 4.81.
4-(4-Chlorophenyl)-1,6-dihydroxy-6-(trifluoromethyl)-
5,6-dihydropyridin-2(1H)-one (7g). Yield 62%, mp 195–
196°С. IR spectrum, ν, cm−1: 3248 (ОН), 1679 (CO), 1624,
1
7.72 (2H, d, J = 8.7, H Ar). Н NMR spectrum (500 MHz,
CDCl3), δ, ppm (J, Hz): 3.18 (1H, ddq, J = 18.4, J = 2.5,
JHF = 1.3) and 3.39 (1H, d, J = 18.4, 5-СН2); 3.65–4.40 (2H,
br. s, NH2); 5.22 (1H, s, OH); 6.33 (1H, d, J = 2.5, 3-CН);
7.42 (4H, s, H Ar). 19F NMR spectrum (471 MHz, CDCl3),
δ, ppm (J, Hz): 79.8 (d, JHF = 1.3, CF3). 13С NMR spectrum
(126 MHz, CDCl3), δ, ppm (J, Hz): 33.7 (C-5); 84.0 (q,
1
1
2JCF = 30.5, С-6); 117.5 (C-3); 124.0 (q, JCF = 291.8, CF3);
1592. Н NMR spectrum (400 MHz, DMSO-d6), δ, ppm
127.1 (2C Ar); 129.3 (2С Ar); 134.5 (C Ar); 136.5 (C Ar);
144.4 (C-4); 164.1 (CO). Found, %: C 47.06; H 3.28; N 9.28.
C12H10ClF3N2O2. Calculated, %: C 47.00; H 3.29; N 9.13.
1-Amino-6-hydroxy-4-(4-methylphenyl)-6-(trifluoro-
methyl)-5,6-dihydropyridin-2(1H)-one (7d). Yield 68%,
mp 179–180°С. IR spectrum, ν, cm−1: 3287 (OH), 1654
(J, Hz): 3.12 (1H, d, J = 18.1) and 3.43 (1H, dd, J = 18.1,
J = 2.1, 5-СН2); 6.41 (1H, d, J = 2.1, 3-CH); 7.50 (2H, d,
J = 8.7, H Ar); 7.72 (2H, d, J = 8.7, H Ar); 7.77 (1H, s, OH);
9.69 (1H, s, ОН). 19F NMR spectrum (376 MHz, DMSO-d6),
δ, ppm: 85.4 (s, CF3). 13C NMR spectrum (101 MHz,
DMSO-d6), δ, ppm (J, Hz): 35.0 (C-5); 86.8 (q, 2JCF = 29.8,
1
1
(CO), 1614. Н NMR spectrum (400 MHz, DMSO-d6),
C-6); 117.3 (C-3); 123.3 (q, JCF = 288.6, CF3); 128.1
δ, ppm (J, Hz): 2.34 (3Н, s, CH3); 3.10 (1H, d, J = 18.0)
and 3.30 (1H, dd, J = 18.0, J = 1.3, 5-СН2); 4.57 (2H, s,
NH2); 6.39 (1H, s, 3-CН); 7.26 (2H, d, J = 8.2, H Ar); 7.37
(1H, s, OH); 7.57 (2H, d, J = 8.2, H Ar). 1Н NMR spectrum
(400 MHz, CDCl3), δ, ppm (J, Hz): 2.39 (3H, s, CH3); 3.17
(1H, d, J = 18.4) and 3.43 (1H, d, J = 18.4, 5-СН2); 4.05
(2H, s, NH2); 5.21 (1H, s, OH); 6.33 (1H, d, J = 2.3,
3-CН); 7.24 (2H, d, J = 8.2, H Ar); 7.39 (2Н, d, J = 8.2,
H Ar). 19F NMR spectrum (376 MHz, CDCl3), δ, ppm: 80.0
(s, CF3). Found, %: C 54.52; H 4.54; N 9.84. C13H13F3N2O2.
Calculated, %: C 54.55; H 4.58; N 9.79.
Synthesis of compounds 7e–h (General method).
Hydroxylamine hydrochloride (87 mg, 1.25 mmol) was
added to a solution of KOH (70 mg, 1.25 mmol) in EtOH
(2 ml). The mixture was stirred for 10 min and the
appropriate pyrone 3 (0.42 mmol) was added. The reaction
mixture was stirred for 5 h (control by TLC method), then
diluted with H2O (10 ml) and ethanol was evaporated at
(2C Ar); 128.7 (2C Ar); 134.7 (C Ar); 134.9 (C Ar); 144.0
(C-4); 164.2 (CO). Found, %: C 46.92; H 2.93; N 4.46.
C12H9ClF3NO3. Calculated, %: C 46.85; H 2.95; N 4.55.
1,6-Dihydroxy-4-(4-methylphenyl)-6-(trifluoromethyl)-
5,6-dihydropyridin-2(1H)-one (7h). Yield 46%, mp 211–
213°С. IR spectrum, ν, cm−1: 3268 (ОН), 1681 (CO), 1627,
1
1609, 1486. Н NMR spectrum (500 MHz, DMSO-d6),
δ, ppm (J, Hz): 2.34 (3H, s, CH3); 3.13 (1H, d, J = 18.0)
and 3.38 (1H, dd, J = 18.0, J = 1.6, 5-СН2); 6.34 (1H, d,
J = 1.8, 3-CH); 7.26 (2H, d, J = 8.1, H Ar); 7.57 (2H, d,
J = 8.1, H Ar); 7.73 (1H, s, OH); 9.64 (1H, s, ОН).
19F NMR spectrum (471 MHz, DMSO-d6), δ, ppm: 85.4 (s,
CF3). Found, %: C 54.32; H 4.15; N 4.52. C13H12F3NO3.
Calculated, %: C 54.36; H 4.21; N 4.88.
Synthesis of pyridinones 9a–c (General method).
Method I. A solution of N2H4·2HCl (82 mg, 0.8 mmol,
2 equiv), anhydrous sodium acetate (158 mg, 2 mmol,
5 equiv) and pyrone 3 (0.4 mmol) in 4:1 mixture of DMF–
1299