Med Chem Res
(DMSO-d6, 600 MHz): 1:0.31 mixture of conformers; sig-
nals for major antiperiplanar conformer about the amide
bond: δ = 7.52 (1H, t, J = 7.2 Hz, H-6), 7.52 (1H, d, J = 7.9
Hz, H-8), 7.77 (1H, t, J = 8.0 Hz, H-7), 7.87 (2H, d, J = 5.4
Hz, H-2′ and H-6′), 8.04 (1H, d, J = 7.8 Hz, H-5), 8.660
(1H, s, CH), 8.81 (2H, d, J = 5.4 Hz, H-3′ and H-5′), 12.37
(1H, s, NH); resolved signals for minor synperiplanar
conformer: δ = 7.73 (2H, d, J = 5.3 Hz, H-2′ and H-6′), 7.96
(1H, d, J = 7.9 Hz, H-5), 8.29 (1H, s, CH), 8.72 (2H, d,
J = 5.3 Hz, H-3′ and H-5′), 12.32 (1H, s, NH); 13C-NMR
(DMSO-d6, 150 MHz): δ = 116.6 (C-8), 118.3 (C-4a),
119.2 (C-3), 121.7 (C-2′ and C-6′), 125.4 (C-6), 126.2 (C-
5), 133.8 (C-7), 140.2 (C-1′), 142.9 (CH), 150.3 (C-3′ and
C-5′), 151.4 (C-8a), 157.7 (C-2), 161.6 (C=O); ESI-MS
m/z: 328.0471 [M+H]+, 350.0290 [M+Na]+; Anal. calcd.
for C16H10ClN3O3: C 58.64; H 3.08; N 12.82. Found: C
58.94; H 2.94; N 12.69.
filtered, washed with aqueous ethanol (2 × 10 mL), and
recrystallized from EtOH to give TLC pure crystals.
N′-[(E)-(2-methyl-2H-chromen-3-yl)methylidene]
benzohydrazide 8a
Yellow solid, yield: 88 %, 0.514 g; m.p. 120–121 °C; FTIR
(ATR) νmax 3341, 1651, 1629, 1601 cm−1; 1H NMR
(DMSO-d6, 600 MHz): δ = 1.33 (3H, d, J = 6.5 Hz, CH3),
5.48 (1H, q, J = 6.5 Hz, H-2), 6.87 (1H, d, J = 8.0 Hz, H-8),
6.93 (1H, s, H-4), 6.94 (1H, t, J = 7.4 Hz, H-6), 7.22 (1H, t,
J = 7.5 Hz, H-7), 7.24 (1H, d, J = 7.6 Hz, H-5), 7.53 (2H, t,
J = 7.5 Hz, H-3′ and H-5′), 7.60 (1H, t, J = 7.3 Hz,
H-4′), 7.88 (2H, d, J = 7.4 Hz, H-2′ and H-6′), 8.15 (1H, s,
CH), 11.81 (1H, s, NH); 13C-NMR (DMSO-d6, 150 MHz):
δ = 19.3 (CH3), 69.7 (C-2), 116.5 (C-8), 121.4 (C-4a),
121.5 (C-6), 127.6 (C-4, C-5, C-2′ and C-6′), 128.5
(C-3′ and C-5′), 130.7 (C-7), 131.8 (C-4′), 133.4 (C-1′),
133.5 (C-3), 146.5 (CH), 152.2 (C-8a), 163.1 (C=O);
ESI-MS m/z: 293.1273 [M+H]+; Anal. calcd. for C18
H16N2O2: C 73.95; H 5.52; N 9.58. Found: C 73.91; H
5.53; N 9.59.
2-Methyl-2H-chromene-3-carbaldehyde 7
To a mixture of 2-hydroxybenzaldehyde 5 (0.85 g, 0.8 mL,
7 mmol) and potassium carbonate (0.97 g, 7 mmol) in 1,4-
dioxane (12.5 mL) crotonaldehyde 6 (0.5 mL) was added
dropwise under vigorous stirring. The mixture was heated at
100 oC for 48 h (monitored by TLC) and allowed to cool.
The reaction was quenched with water and extracted several
times with ether (Suslov et al., 2009; Azizmohammadi
et al., 2013). The combined ether extracts were dried
(Na2SO4) and evaporated to give raw compound as a yellow
oil. The product was purified by silica gel column chro-
matography (hexane–EtOAc mixture 10:1) to give
2-methyl-2H-chromene-3-carbaldehyde 7. Oil, 0.7 g, yield
4-hydroxy-N′-[(E)-(2-methyl-2H-chromen-3-yl)
methylidene]benzohydrazide 8b
Yellow solid, yield 86 %, 0.530 g; m.p. 257–258 oC; FTIR
1
(ATR) νmax 3508, 3379, 1659, 1625, 1604 cm−1; H NMR
(DMSO-d6, 600 MHz): δ = 1.31 (3H, d, J = 6.4 Hz,
CH3), 5.46 (1H, q, J = 6.4 Hz, H-2), 6.85 (2H, d, J = 8.5
Hz, H-3′ and H-5′), 6.86 (1H, d, J = 8.3 Hz, H-8), 6.88 (1H,
s, H-4), 6.93 (1H, dt, J = 0.9, 7.4 Hz, H-6), 7.20 (1H, dt,
J = 1.6, 7.7 Hz, H-7), 7.23 (1H, dd, J = 1.5, 7.5 Hz,
H-5), 7.77 (2H, d, J = 8.5 Hz, H-2′ and H-6′), 8.12 (1H, s,
CH), 10.16 (1H, s, OH), 11.60 (1H, s, NH); 13C-NMR
(DMSO-d6, 150 MHz,): δ = 19.3 (CH3), 69.7 (C-2), 115.1
(C-3′ and C-5′), 116.5 (C-8), 121.5 (C-6), 121.5 (C-4a),
123.8 (C-1′), 127.0 (C-4), 127.6 (C-5), 129.7 (C-2′
and C-6′), 130.6 (C-7), 133.7 (C-3), 145.6 (CH), 152.2
(C-8a), 160.8 (C-4′), 162.7 (C=O). ESI-MS m/z: 309.28
[M+H]+, 331.20 [M+Na]+; Anal. calcd. for C18H16N2O3:
C 70.12, H 5.23, N 9.09. Found: C 70.14, H, 5.28,
N 9.10.
1
57 %; FTIR (ATR) νmax 2975, 2809, 1664, 1627 cm−1; H
NMR (DMSO-d6; 600 MHz,): δ = 1.22 (3H, d, J = 6.5 Hz,
CH3), 5.28 (1H, q, J = 6.5 Hz, H-2), 6.88 (1H, d, J = 8.2
Hz, H-9), 6.99 (1H, dt, J = 1.1, 7.5 Hz, H-7), 7.34 (1H, ddd,
J = 1.7, 8.2, 7.4 Hz, H-8), 7.38 (1H, dd, J = 1.6, 7.5 Hz, H-
6), 7.57 (1H, s, H-4), 9.53 (1H, s, CHO); 13C-NMR
(DMSO-d6, 150 MH): δ = 19.8 (CH3), 69.1 (C-2), 117.0 (C-
9), 120.0 (C-5), 121.9 (C-7), 129.8 (C-6), 133.6 (C-8),
135.7 (C-3), 140.3 (C-4), 153.7 (C-10), 191.0 (CHO); ESI-
MS m/z: 174.0676 [M+] (100).
General synthetic procedure for compounds 8a–c
N′-[(E)-(2-methyl-2H-chromen-3-yl)methylidene]pyridine-
4-carbohydrazide 8c
An equimolecular amount of the appropriate hydrazide
3a–c (2.0 mmol) in 10 mL abs. EtOH was added to a
solution of 2-methyl-2H-chromene-3-carbaldehyde 7 (2.0
mmol) in 10 mL abs. EtOH under vigorous stirring at 25 °C
for 30 min. The reaction mixture turned into yellow solu-
tion. After 2–8 h the clusters of yellow crystalline com-
pounds 8a–c deposited from the solution. They were
Yellow solid, yield 92 %, 0.539 g; m.p. 122–123 oC, FTIR
(ATR) νmax 3418, 1660, 1626, 1605 cm−1; 1H NMR
(DMSO-d6, 600 MHz): δ = 1.33 (3H, d, J = 6.5 Hz, CH3),
5.47 (1H, q, J = 6.5 Hz, H-2), 6.88 (1H, d, J = 8.0 Hz, H-8),
6.94 (1H, t, J = 7.4 Hz, H-6), 7.23 (1H, t, J = 7.6 Hz, H-7),
7.25 (1H, d, J = 7.6 Hz, H-5), 6.98 (1H, s, H-4), 7.79 (2H,