Modified Coumarins. 34. Synthesis and Transformations of Angular α-Pyronoflavanones

Full text of DOI:10.1007/s10600-015-1427-0

DOI 10.1007/s10600-015-1427-0
Chemistry of Natural Compounds, Vol. 51, No. 5, September, 2015
MODIFIED COUMARINS. 34. SYNTHESIS AND TRANSFORMATIONS
OF ANGULAR ꢀ-PYRONOFLAVANONES
*
Yu. A. Nikitina, Ya. L. Garazd, and M. M. Garazd
Syntheses of angular ꢀ-pyronoflavanones were described. Their reactions with nucleophiles were studied.
Keywords: coumarins, flavonoids, flavanones, ꢀ-pyronoflavanones, pyrazolines, heterocyclization.
Flavonoids are the most broadly distributed natural compounds of plant origin and occur in practically all species.
The flavonoid class currently numbers about 6,500 natural compounds [1]. The heightened interest in flavonoids is due to the
important role these compounds play in plant and animal metabolism and their high and varied biological activity [2]. Flavonoids
are subdivided into several types, the most common of which are flavanones, the structures of which are based on the
2-arylchromane skeleton. The coumarin core is also included in the structures of many important natural compounds [3] and
substances with high pharmacological activity [4]. Therefore, the combination in a single molecule of the flavanone and
coumarin cores seems interesting for both flavonoid and coumarin chemistry and targeted synthesis of new biologically active
compounds. Herein we present results for the synthesis of angular ꢀ-pyronoflavanones and the study of their reactions with
nucleophiles.
5-Hydroxy-7-methylcoumarins 1–4 were required for further transformations and were prepared via a Pechmann
reaction of orcinol and the appropriate ethylacylacetates in the presence of a condensing agent (conc. H SO ). Acetylation of
2
4
hydroxycoumarins 1–4 by acetic anhydride in Py formed 5-acetoxycoumarins 5–8, Fries rearrangement of which in the presence
of anhydrous AlCl at 120–130°C afforded in high yields 6-acetylcoumarins 9–12.
3
Reactions of 9–12 and aromatic aldehydes with heating in EtOH in the presence of catalytic amounts of pyrrolidine
led to annelation of a 2-aryltetrahydropyran-4-one ring and formation of 2-aryl-10-alkyl-5-methyl-2,3-dihydropyrano
[2,3-f]chromen-4,8-diones 13–35 [5, 6]. Obviously, the angular ꢀ-pyronoflavanones formed via the corresponding intermediate
chalcones, which heterocyclized smoothly under the synthetic conditions. PMR spectra of 13–35 showed resonances for
H-2 (5.59–6.16 ppm, dd, J = 2.4 and 13.6 Hz), equatorial H-3 (2.66–2.83 ppm, dd, J = 2.4 and 16.8 Hz), and axial H-3
(3.20–3.51 ppm, dd, J = 13.6 and 16.8 Hz), which were characteristic resonances for flavanone protons [7, 8].
Hydrazine is known to react with flavanones to give various compounds depending on the reaction conditions. In
particular, the principal products can be hydrazones of flavanones, 3-(2-hydroxyphenyl)-5-phenylpyrazolines, or azines of
flavanones [9, 10]. We found that the flavanone core recyclized upon heating EtOH solutions of 13–35 with a five-fold excess
of hydrazine hydrate and formed 6-[5-aryl-4,5-dihydropyrazol-3-yl]-4-alkyl-5-hydroxy-7-methylcoumarins 36–47, the PMR
spectra of which contained resonances characteristic of the coumarin and pyrazoline moieties [11]. In particular, the methylene
diastereotopic protons resonated at 3.09–3.45 and 3.72–3.88 ppm (dd, J = 10.4 and 16.4 Hz) whereas pyrazoline H-5 was
observed as a multiplet at 4.75–5.43 ppm. A characteristic feature of the PMR spectra of 36–47 was the separate absorption of
the NH and OH protons. The NH proton appeared as a doublet with SSCC J = 3.6 Hz in the range 7.60–7.82 ppm.
The presence of the hydroxyl proton resonance at weak field (13.65–14.05 ppm) was indicative of an intramolecular interaction
between it and the pyrazoline N atom. Compounds 36–47 gave a characteristic brownish-green chelate complex in an EtOH
solution of FeCl because of the coumarin phenol hydroxyl and the pyrazoline N atom.
3
The reaction of 25 and phenylhydrazine in EtOH did not involve recyclization even with prolonged heating but
formed the corresponding phenylhydrazone of ꢀ-pyronoflavanone 48.
The reaction of 25 and hydroxylamine in Py also did not involve recyclization but gave the corresponding oxime of
ꢀ-pyronoflavanone 49.
Eximed, 02160, Ukraine, Kiev, Kharkovskoe Shosse, 50, e-mail: gmm@i.com.ua. Translated from Khimiya Prirodnykh
Soedinenii, No. 5, September–October, 2015, pp. 713–717. Original article submitted March 9, 2015.
©
0009-3130/15/5105-0829 2015 Springer Science+Business Media New York
829

Me
Me
O
R
O
Me
Me
O
O
Me
Me
O
R
O
Ac O, Py
2
AlCl
Ar-CHO
3
OH
OH
O
R
O
OH
1 - 4
5 - 8
9 - 12
O
O
R
O
Me
O
O
Me
O
R
O
O
N H
2
O
4
Ar
O
R
OH
N
N
H
Ar
13 - 35
36 - 47
Ar
NH OH
2
PhNHNH
2
Me
O
O
Me
O
O
Ph
N
N
N
H
HO
O
Et
O
Et
49
48
OMe
OMe
O
O
21, 26, 44: Ar =
OMe
1, 5, 9: R = CH ; 2, 6, 10: R = CH CH ; 3, 7, 11: CH CH CH ; 4, 8, 12: CH CH CH CH ; 13, 36: R = CH , Ar = 4-ClC H
6 4
3
2
3
2
2
3
2
2
2
3
3
14, 37: R = CH , Ar = 4-CH OC H ; 15, 38: R = CH , Ar = 4-(CH ) NC H ; 16, 39: R = CH , Ar = 2-CH OC H
3
3
6
4
3
3 2
6
4
3
3
6 4
17, 40: R = CH , Ar = 2,4-(CH O) C H ; 18, 41: R = CH , Ar = 2-Cl-6-FC H ; 19, 42: R = CH , Ar = 2,3,4-(CH O) C H
3
3
2
6
3
3
6
3
3
3
3 6 2
20, 43: R = CH , Ar = 2,4,5-(CH O) C H ; 22, 45: CH CH , Ar = 4-ClC H ; 21, 44: R = CH ; Ar = X
3
3
3
6
2
2
3
6
4
3
23, 46: R = CH CH , Ar = 4-CH OC H 24, 47: R = CH CH , Ar = 4-(CH ) NC H ; 25: R = CH CH , Ar = 3-HO-4-CH OC H
2
3
3
6
4
2
3
3 2
6
4
2
3
3
6 3
26: R = CH CH , Ar = X; 27: CH CH CH , Ar = 4-CH C H 28: R = CH CH CH , Ar = 4-CH OC H
2
3
2
2
3
3
6
4
2
2
3
3
6 4
29: R = CH CH CH , Ar = 4-(CH ) NC H ; 30: R = CH CH CH , Ar = 2,4-(CH O) C H
2
2
3
3 2
6
4
2
2
3
3
2 6 3
31: CH CH CH , Ar = 2,3,4-(CH O) C H ; 32: R = CH CH CH CH , Ar = 3,4-(CH O) C H ;
2
2
3
3
3
6
2
2
2
2
3
3
2 6 3
33: R = CH CH CH CH , Ar = 4-HO-3-CH OC H 34: R = CH CH CH CH , Ar = 4-HO-3,5-(CH O) C H
2
2
2
3
3
6
3
2
2
2
2
3
3
2
6
3
35: R = CH CH CH CH , Ar = 2,3,4-(CH O) C H
2
2
2
3
3
3 6
EXPERIMENTAL
General. The course of reactions and purity of products were monitored by TLC on Merck 60 F254 plates using
CHCl –MeOH (9:1 and 95:5). Melting points were measured on a Kofler apparatus. NMR spectra were recorded relative to
3
TMS internal standard on a Varian Mercury 400 spectrometer at 400 MHz. Elemental analyses of all compounds agreed with
those calculated.
Coumarins 1–12 were obtained as before [12].
2-Aryl-10-alkyl-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-diones (13–35). A mixture of 6-acetyl-5-
hydroxycoumarin (9–12, 4 mmol) and the appropriate aromatic aldehyde (4.8 mmol) in EtOH was refluxed for 5–6 h in the
presence of catalytic amounts (1–2 drops) of pyrrolidine (end of reaction determined by TLC). The reaction mixture was
cooled. The resulting precipitate was filtered off and crystallized from EtOH.
2-(4-Chlorophenyl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (13). Yield 74%, mp 211–212ꢁÑ,
1
Ñ Í ClÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.42 (3Í, s, ÑÍ -10), 2.65 (3Í, s, ÑÍ -5), 2.83 (1H,
20 15
4
6
3
3
dd, J = 2.4, 16.8, Í-3 ), 3.24 (1H, dd, J = 13.6, 16.8, Í-3 ), 5.78 (1H, dd, J = 2.4, 13.6, Í-2), 6.23 (1Í, s, Í-9), 6.93 (1Í, s,
eq
ax
Í-6), 7.53 (2Í, d, J = 8.4, H-3ꢃ, 5ꢃ), 7.63 (2Í, d, J = 8.4, H-2ꢃ, 6ꢃ).
2-(4-Methoxyphenyl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (14). Yield 63%, mp 197–197ꢁÑ,
1
Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.43 (3Í, s, ÑÍ -10), 2.62 (3Í, s, ÑÍ -5), 2.81 (1H, dd,
21 18
5
6
3
3
830

J = 2.4, 16.8, Í-3 ), 3.23 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.80 (3Í, s, ÎÑÍ -4ꢃ), 5.69 (1H, dd, J = 2.4, 13.6, Í-2), 6.20 (1Í,
eq
ax
3
s, Í-9), 6.90 (1Í, s, Í-6), 7.02 (2Í, d, J = 8.4, H-3ꢃ, 5ꢃ), 7.52 (2Í, d, J = 8.4, H-2ꢃ, 6ꢃ).
2-[4-(Dimethylamino)phenyl]-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (15). Yield 59%,
1
mp 229–230ꢁÑ, Ñ Í NÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.41 (3Í, s, ÑÍ -10), 2.65 (3Í, s, ÑÍ -5),
22 21
4
6
3
3
2.76 (1H, dd, J = 2.4, 16.8, Í-3 ), 2.93 (6H, s, N(CH ) ), 3.21 (1H, dd, J = 13.6, 16.8, Í-3 ), 5.59 (1H, dd, J = 2.4, 13.6,
eq
3 2
ax
Í-2), 6.17 (1Í, s, Í-9), 6.76 (2Í, d, J = 8.0, H-3ꢃ, 5ꢃ), 6.87 (1Í, s, Í-6), 7.37 (2Í, d, J = 8.0, H-2ꢃ, 6ꢃ).
2-(2-Methoxyphenyl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (16). Yield 62%, mp 188–189ꢁÑ,
1
Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.45 (3Í, s, ÑÍ -10), 2.65 (3Í, s, ÑÍ -5), 2.79 (1H, dd,
21 18
5
6
3
3
J = 2.4, 16.8, Í-3 ), 3.20 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.84 (3Í, s, ÎÑÍ -2ꢃ), 5.91 (1H, dd, J = 2.4, 13.6, Í-2), 6.23 (1Í, s,
eq
ax
3
Í-9), 6.93 (1Í, s, Í-6), 7.07 (1Í, t, J = 7.6, H-5ꢃ), 7.12 (2Í, d, J = 8.4, H-3ꢃ), 7.41 (1Í, t, J = 7.6, H-4ꢃ), 7.59 (2Í, d, J = 8.0,
H-6ꢃ).
2-(2,4-Dimethoxyphenyl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (17). Yield 76%, mp 201–
1
202ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.44 (3Í, s, ÑÍ -10), 2.67 (3Í, s, ÑÍ -5), 2.79
22 20
6
6
3
3
(1H, dd, J = 2.4, 16.8, Í-3 ), 3.26 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.82 and 3.84 (6Í, two s, ÎÑÍ -2ꢃ, 4ꢃ), 5.83 (1H, dd,
eq
ax
3
J = 2.4, 13.6, Í-2), 6.19 (1Í, s, Í-9), 6.61 (2Í, dd, J = 2.4, 8.4, H-5ꢃ), 6.66 (2Í, d, J = 2.4, H-3ꢃ), 6.90 (1Í, s, Í-6), 7.47 (2Í,
d, J = 8.4, H-6ꢃ).
2-(2-Chloro-6-fluorophenyl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (18). Yield 81%,
1
mp 221–222ꢁÑ, Ñ Í ClFÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.36 (3Í, s, ÑÍ -10), 2.66 (3Í, s,
20 14
5
6
3
ÑÍ -5), 2.84 (1H, dd, J = 2.4, 16.8, Í-3 ), 3.51 (1H, dd, J = 13.6, 16.8, Í-3 ), 6.16 (1H, dd, J = 2.4, 13.6, Í-2), 6.22 (1Í, s,
3
eq
ax
Í-9), 6.95 (1Í, s, Í-6), 7.39–7.56 (3H, m, H-3ꢃ, 4ꢃ, 5ꢃ).
5,10-Dimethyl-2-(2,3,4-trimethoxyphenyl)-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (19). Yield 85%,
1
mp 194–196ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.43 (3Í, s, ÑÍ -10), 2.67 (3Í, s, ÑÍ -5),
23 22
7
6
3
3
2.70 (1H, dd, J = 2.4, 16.8, Í-3 ), 3.25 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.80 and 3.85 (9Í, two s, ÎÑÍ -2ꢃ, 3ꢃ, 4ꢃ), 5.83 (1H,
eq
ax
3
dd, J = 2.4, 13.6, Í-2), 6.20 (1Í, s, Í-9), 6.91 (1Í, s, Í-6), 6.92 (2Í, d, J = 8.8, H-5ꢃ), 7.32 (2Í, d, J = 8.8, H-6ꢃ).
5,10-Dimethyl-2-(2,4,5-trimethoxyphenyl)-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (20). Yield 72%, mp 198–
1
199ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.45 (3Í, s, ÑÍ -10), 2.65 (3Í, s, ÑÍ -5), 2.68
23 22
7
6
3
3
(1H, dd, J = 2.4, 16.8, Í-3 ), 3.24 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.74, 3.82 and 3.84 (9Í, three s, ÎÑÍ -2ꢃ, 4ꢃ, 5ꢃ), 5.83 (1H,
eq
ax
3
dd, J = 2.4, 13.6, Í-2), 6.22 (1Í, s, Í-9), 6.78 (2Í, s, H-3ꢃ), 6.92 (1Í, s, Í-6), 7.20 (2Í, s, H-6ꢃ).
2-(8-Methoxy-1,4-benzodioxan-6-yl)-5,10-dimethyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (21). Yield 74%,
1
mp 201–202ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.46 (3Í, s, ÑÍ -10), 2.64 (3Í, s,
23 20
7
6
3
ÑÍ -5), 2.76 (1H, dd, J = 2.4, 16.8, Í-3 ), 3.26 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.76 (3Í, s, ÎÑÍ -8ꢃ), 4.24 (4Í, s, ÑÍ -2ꢃ,
3
eq
ax
3
2
3ꢃ), 5.60 (1H, dd, J = 2.4, 13.6, Í-2), 6.22 (1Í, s, Í-9), 6.71 (2Í, s, H-5ꢃ), 6.84 (2Í, s, H-7ꢃ), 6.91 (1Í, s, Í-6).
2-(4-Chlorophenyl)-10-ethyl-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (22). Yield 71%, mp 191–
1
192ꢁÑ, Ñ Í ClÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.02 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.66 (3Í, s,
21 17
4
6
3
ÑÍ -5), 2.75–2.85 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.23 (1H, dd, J = 13.6, 16.8, Í-3 ), 5.71 (1H, dd, J = 2.4, 13.6, Í-2), 6.11 (1Í, s,
3
eq
2
ax
Í-9), 6.86 (1Í, s, Í-6), 7.45 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 7.58 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ).
10-Ethyl-2-(4-methoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (23). Yield 63%, mp 159–
1
160ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.06 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.68 (3Í, s, ÑÍ -5),
22 20
5
6
3
3
2.74 (1H, dd, J = 2.8, 16.8, Í-3 ), 2.78–2.85 (2H, m, ÑÍ -1ꢃ), 3.21 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.82 (3Í, s, ÎÑÍ -4ꢃꢃ),
eq
2
ax
3
5.60 (1H, dd, J = 2.8, 13.6, Í-2), 6.08 (1Í, s, Í-9), 6.83 (1Í, s, Í-6), 6.95 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 7.46 (2Í, d, J = 8.4,
H-3ꢃꢃ, 5ꢃꢃ).
2-(4-Dimethylaminophenyl)-10-ethyl-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (24). Yield 78%,
1
mp 193–194ꢁÑ, Ñ Í NÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.05 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.66 (3Í, s,
23 23
4
6
3
ÑÍ -5), 2.70 (1H, dd, J = 2.4, 16.8, Í-3 ), 2.76–2.84 (2H, m, ÑÍ -1ꢃ), 2.97 (6Í, s, (CH ) N), 3.23 (1H, dd, J = 13.6, 16.8,
3
eq
2
3 2
Í-3 ), 5.52 (1H, dd, J = 2.4, 13.6, Í-2), 6.09 (1Í, s, Í-9), 6.72 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 6.83 (1Í, s, Í-6), 7.34 (2Í, d,
ax
J = 8.4, H-3ꢃꢃ, 5ꢃꢃ).
10-Ethyl-2-(3-hydroxy-4-methoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (25). Yield
1
56%, mp 210–211ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.06 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.66 (3Í,
22 20
6
6
3
s, ÑÍ -5), 2.70 (1H, dd, J = 2.4, 16.8, Í-3 ), 2.76–2.84 (2H, m, ÑÍ -1ꢃ), 3.25 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.82 (3Í, s,
3
eq
2
ax
ÎÑÍ -4ꢃꢃ), 5.62 (1H, dd, J = 2.4, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.91 (1Í, s, Í-6), 6.97–7.01 (3Í, m, Í-2ꢃꢃ, 5ꢃꢃ, 6ꢃꢃ), 8.95 (1Í,
3
br.s, ÎÍ-3ꢃꢃ).
831

10-Ethyl-2-(8-methoxy-1,4-benzodioxan-6-yl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (26). Yield
1
76%, mp 206–207ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.07 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.65
24 22
7
6
3
(3Í, s, ÑÍ -5), 2.70 (1H, dd, J = 2.4, 16.8, Í-3 ), 2.76–2.86 (2H, m, ÑÍ -1ꢃ), 3.25 (1H, dd, J = 13.6, 16.8, Í-3 ), 3.79 (3Í,
3
eq
2
ax
s, ÎÑÍ -8ꢃꢃ), 4.25 (4H, s, ÑÍ -2ꢃꢃ, 3ꢃꢃ), 5.59 (1H, dd, J = 2.4, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.71 (1Í, s, Í-5ꢃꢃ), 6.83 (1Í, s,
3
2
Í-7ꢃꢃ), 6.90 (1Í, s, Í-6).
5-Methyl-2-(4-methylphenyl)-10-propyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (27). Yield 82%, mp 177–
1
178ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.58 (3Í, t, J = 7.2, ÑÍ -3ꢃ), 1.35–1.45 (2H, m,
23 22
4
6
3
ÑÍ -2ꢃ), 2.39 (3Í, s, ÑÍ -4ꢃꢃ), 2.62–2.70 (2H, m, ÑÍ -1ꢃ), 2.68 (3Í, s, ÑÍ -5), 2.74 (1H, dd, J = 2.8, 16.8, Í-3 ), 3.21 (1H,
2
3
2
3
eq
dd, J = 13.6, 16.8, Í-3 ), 5.59 (1H, dd, J = 2.8, 13.6, Í-2), 6.05 (1Í, s, Í-9), 6.84 (1Í, s, Í-6), 7.23 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ),
ax
7.42 (2Í, d, J = 8.4, H-2ꢃꢃ, 6ꢃꢃ).
2-(4-Methoxyphenyl)-5-methyl-10-propyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (28). Yield 64%, mp 181–
1
182ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.50 (3Í, t, J = 7.2, ÑÍ -3ꢃ), 1.40–1.48 (2H, m,
23 22
5
6
3
ÑÍ -2ꢃ), 2.62–2.75 (3H, m, Í-3 , ÑÍ -1ꢃ), 2.70 (3Í, s, ÑÍ -5), 3.40 (1H, dd, J = 14.0, 16.4, Í-3 ), 3.80 (3Í, s, OÑÍ -4ꢃꢃ),
2
eq
2
3
ax
3
5.67 (1H, dd, J = 2.0, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.94 (1Í, s, Í-6), 7.30 (2Í, d, J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 7.54 (2Í, d, J = 8.8,
H-2ꢃꢃ, 6ꢃꢃ).
2-(4-Dimethylaminophenyl)-5-methyl-10-propyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (29). Yield 76%,
1
mp 181–182ꢁÑ, Ñ Í NÎ . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.53 (3Í, t, J = 7.2, ÑÍ -3ꢃ), 1.38–1.45
24 25
4
6
3
(2H, m, ÑÍ -2ꢃ), 2.62–2.75 (3H, m, Í-3 , ÑÍ -1ꢃ), 2.65 (3Í, s, ÑÍ -5), 2.93 (6Í, s, (CH ) N), 3.35 (1H, dd, J = 14.0, 16.4,
2
eq
2
3
3 2
Í-3 ), 5.57 (1H, dd, J = 2.0, 13.6, Í-2), 6.15 (1Í, s, Í-9), 6.77 (2Í, d, J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 6.90 (1Í, s, Í-6), 7.39 (2Í, d,
ax
J = 8.8, H-2ꢃꢃ, 6ꢃꢃ).
2-(2,4-Dimethoxyphenyl)-5-methyl-10-propyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (30). Yield 81%,
1
mp 178–179ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.56 (3Í, t, J = 7.2, ÑÍ -3ꢃ), 1.35–1.42
24 24
6
6
3
(2H, m, ÑÍ -2ꢃ), 2.65 (3Í, s, ÑÍ -5), 2.65–2.75 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.42 (1H, dd, J = 14.0, 16.4, Í-3 ), 3.81 and 3.82
2
3
eq
2
ax
(6Í, two s, ÎÑÍ -2ꢃꢃ, 4ꢃꢃ), 5.83 (1H, dd, J = 2.4, 13.6, Í-2), 6.17 (1Í, s, Í-9), 6.62 (2Í, dd, J = 2.4, 8.4, H-5ꢃꢃ), 6.66 (2Í, d,
3
J = 2.4, H-3ꢃꢃ), 6.92 (1Í, s, Í-6), 7.50 (2Í, d, J = 8.4, H-6ꢃꢃ).
5-Methyl-10-propyl-2-(3,4,5-trimethoxyphenyl)- 2,3-dihydropyrano[2,3-f]chromen-4,8-dione (31). Yield 81%,
1
mp 172–173ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.50 (3Í, t, J = 7.2, ÑÍ -3ꢃ), 1.38–1.45
25 26
7
6
3
(2H, m, ÑÍ -2ꢃ), 2.63–2.78 (3H, m, Í-3 , ÑÍ -1ꢃ), 2.65 (3Í, s, ÑÍ -5), 3.46 (1H, dd, J = 14.0, 16.4, Í-3 ), 3.68 (3Í, s,
2
eq
2
3
ax
ÎÑÍ -4ꢃꢃ), 3.81 (6Í, s, ÎÑÍ -3ꢃꢃ, 5ꢃꢃ), 5.63 (1H, dd, J = 2.4, 13.6, Í-2), 6.19 (1Í, s, Í-9), 6.93 (1Í, s, Í-6), 6.96 (2Í, s,
3
3
H-2ꢃꢃ, 6ꢃꢃ).
10-Butyl-2-(3,4-dimethoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (32). Yield 59%,
1
mp 169–170ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.65 (3Í, t, J = 7.2, ÑÍ -4ꢃ), 0.76–0.95
25 26
6
6
3
(2H, m, ÑÍ -3ꢃ), 1.24–1.38 (2H, m, ÑÍ -2ꢃ), 2.66 (3Í, s, ÑÍ -5), 2.67–2.78 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.48 (1H, dd, J = 14.0,
2
2
3
eq
2
16.4, Í-3 ), 3.78 and 3.79 (6Í, two s, ÎÑÍ -3ꢃꢃ, 4ꢃꢃ), 5.65 (1H, dd, J = 2.4, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.95 (1Í, s, Í-6), 7.02
ax
3
(1Í, d, J = 8.0, H-5ꢃꢃ), 7.02 (1Í, dd, J = 2.0, 8.0, H-6ꢃꢃ), 7.26 (1Í, d, J = 2.0, H-2ꢃꢃ).
10-Butyl-2-(4-hydroxy-3-methoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (33). Yield
1
68%, mp 178–179ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.66 (3Í, t, J = 7.2, ÑÍ -4ꢃ), 0.75–
24 24
6
6
3
0.92 (2H, m, ÑÍ -3ꢃ), 1.26–1.39 (2H, m, ÑÍ -2ꢃ), 2.66 (3Í, s, ÑÍ -5), 2.66–2.75 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.46 (1H, dd, J = 14.0, 16.4,
2
2
3
eq
2
Í-3 ), 3.80 (3Í, s, ÎÑÍ -3ꢃꢃ), 5.62 (1H, dd, J = 2.4, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.76 (1Í, d, J = 8.4, H-5ꢃꢃ), 6.94 (1Í, s, Í-6), 7.03
ax
3
(1Í, dd, J = 2.0, 8.4, H-6ꢃꢃ), 7.21 (1Í, d, J = 2.0, H-2ꢃꢃ), 9.21 (1Í, s, ÎÍ-4ꢃꢃ).
10-Butyl-2-(4-hydroxy-3,5-dimethoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (34). Yield
1
72%, mp 187–188ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.66 (3Í, t, J = 7.2, ÑÍ -4ꢃ), 0.72–
25 26
7
6
3
0.94 (2H, m, ÑÍ -3ꢃ), 1.29–1.39 (2H, m, ÑÍ -2ꢃ), 2.66 (3Í, s, ÑÍ -5), 2.66–2.74 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.48 (1H, dd,
2
2
3
eq
2
J = 14.0, 16.4, Í-3 ), 3.79 (6Í, s, ÎÑÍ -3ꢃꢃ, 5ꢃꢃ), 5.59 (1H, dd, J = 2.4, 13.6, Í-2), 6.19 (1Í, s, Í-9), 6.94 (1Í, s, Í-6), 6.91
ax
3
(2Í, s, H-2ꢃꢃ, 6ꢃꢃ), 8.55 (1Í, s, ÎÍ-4ꢃꢃ).
10-Butyl-5-methyl-2-(2,3,4-trimethoxyphenyl)-2,3-dihydropyrano[2,3-f]chromen-4,8-dione (35). Yield 59%,
1
mp 169–170ꢁÑ, Ñ Í Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 0.64 (3Í, t, J = 7.2, ÑÍ -4ꢃ), 0.78–0.92
25 26
7
6
3
(2H, m, ÑÍ -3ꢃ), 1.26–1.32 (2H, m, ÑÍ -2ꢃ), 2.66 (3Í, s, ÑÍ -5), 2.66–2.75 (3H, m, Í-3 , ÑÍ -1ꢃ), 3.42 (1H, dd, J = 14.0,
2
2
3
eq
2
16.4, Í-3 ), 3.79, 3.83 and 3.84 (9Í, three s, ÎÑÍ -2ꢃꢃ, 3ꢃꢃ, 4ꢃꢃ), 5.84 (1H, dd, J = 2.4, 13.6, Í-2), 6.18 (1Í, s, Í-9), 6.93 (2Í,
ax
3
d, J = 8.4, H-5ꢃꢃ), 6.94 (1Í, s, Í-6), 7.36 (2Í, d, J = 8.4, H-6ꢃꢃ).
832

6-[5-Aryl-4,5-dihydropyrazol-3-yl]-4-alkyl-5-hydroxy-7-methylchromen-2-ones (36–47). A mixture of 13–35
(2 mmol) and hydrazine monohydrate (0.50 mL, 10 mmol) in EtOH was refluxed for 2–3 h (end of reaction determined by
TLC). The reaction mixture was cooled. The resulting precipitate was filtered off and crystallized from EtOH.
6-[5-(4-Chlorophenyl)-4,5-dihydropyrazol-3-yl]-5-hydroxy-4,7-dimethylchromen-2-one (36). Yield 58%,
1
mp 231–232ꢁÑ, Ñ Í ClN Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.48 (3Í, s, ÑÍ -7), 2.61 (3Í, s,
20 17
2
3
6
3
ÑÍ -4), 3.15 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.80 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 4.88 (1H, m, Í-5ꢃ), 6.11 (1Í, s, Í-3), 6.71 (1Í,
3
s, Í-8), 7.43 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 7.47 (2Í, d, J = 8.4, H-2ꢃꢃ, 6ꢃꢃ), 7.82 (1H, d, J = 3.6, NH), 13.65 (1Í, s, ÎÍ-5).
5-Hydroxy-6-[5-(4-methoxyphenyl)-4,5-dihydropyrazol-3-yl]- 4,7-dimethylchromen-2-one (37). Yield 52%,
1
mp 218–219ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.49 (3Í, s, ÑÍ -7), 2.61 (3Í, s,
21 20
2
4
6
3
ÑÍ -4), 3.17 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.74 (3Í, s, ÎÑÍ -4ꢃꢃ), 3.75 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 4.81 (1H, m, Í-5ꢃ),
3
3
6.13 (1Í, s, Í-3), 6.72 (1Í, s, Í-8), 6.93 (2Í, d, J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 7.35 (2Í, d, J = 8.8, H-2ꢃꢃ, 6ꢃꢃ), 7.80 (1H, d, J = 3.6, NH),
13.90 (1Í, s, ÎÍ-5).
6-[5-(4-Dimethylaminophenyl)-4,5-dihydropyrazol-3-yl]-5-hydroxy-4,7-dimethylchromen-2-one (38). Yield
1
63%, mp 235–236ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.50 (3Í, s, ÑÍ -7), 2.62 (3Í, s,
22 23
3
3
6
3
ÑÍ -4), 2.88 (6Í, s, (CH ) N), 3.16 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.73 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 4.75 (1H, m, Í-5ꢃ), 6.14
3
3 2
(1Í, s, Í-3), 6.72 (1Í, s, Í-8), 6.72 (2Í, d, J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 7.23 (2Í, d, J = 8.8, H-2ꢃꢃ, 6ꢃꢃ), 7.71 (1H, d, J = 3.6, NH), 13.95
(1Í, s, ÎÍ-5).
5-Hydroxy-6-[5-(2-methoxyphenyl)-4,5-dihydropyrazol-3-yl]- 4,7-dimethylchromen-2-one (39). Yield 52%,
1
mp 219–220ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.48 (3Í, s, ÑÍ -7), 2.60 (3Í, s,
21 20
2
4
6
3
ÑÍ -4), 3.09 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.78 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 3.83 (3Í, s, ÎÑÍ -2ꢃꢃ), 5.06 (1H, m, Í-5ꢃ),
3
3
6.11 (1Í, s, Í-3), 6.70 (1Í, s, Í-8), 6.97 (1Í, t, J = 7.6, H-5ꢃ), 7.03 (2Í, d, J = 8.4, H-3ꢃ), 7.28 (1Í, t, J = 7.6, H-4ꢃ), 7.42 (2Í,
d, J = 8.0, H-6ꢃ), 7.68 (1H, d, J = 3.6, NH), 13.90 (1Í, s, ÎÍ-5).
6-[5-(2,4-Dimethoxyphenyl)-4,5-dihydropyrazol-3-yl]-5-hydroxy-4,7-dimethylchromen-2-one (40). Yield 57%,
1
mp 228–229ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.48 (3Í, s, ÑÍ -7), 2.60 (3Í, s,
22 22
2
5
6
3
ÑÍ -4), 3.09 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.72 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 3.76 and 3.80 (6Í, two s, ÎÑÍ -2ꢃꢃ, 4ꢃꢃ), 4.98
3
3
(1H, m, H-5ꢃ), 6.12 (1Í, s, Í-3), 6.52 (2Í, dd, J = 2.0, 8.0, H-5ꢃꢃ), 6.58 (2Í, d, J = 2.0, H-3ꢃꢃ), 6.70 (1Í, s, Í-8), 7.30 (2Í, d,
J = 8.0, H-6ꢃ), 7.60 (1H, d, J = 3.6, NH), 13.94 (1Í, s, ÎÍ-5).
6-[5-(2-Chloro-6-fluorophenyl)-4,5-dihydropyrazol-3-yl]-5-hydroxy-4,7-dimethylchromen-2-one (41). Yield
1
49%, mp 237–238ꢁÑ, Ñ Í FClN Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.49 (3Í, s, ÑÍ -7), 2.63
20 16
2
3
6
3
(3Í, s, ÑÍ -4), 3.45 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.88 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 5.43 (1H, m, Í-5ꢃ), 6.13 (1Í, s, Í-3),
3
6.73 (1Í, s, Í-8), 7.21–7.41 (3H, m, H-3ꢃꢃ, 4ꢃꢃ, 5ꢃꢃ), 7.74 (1H, d, J = 3.6, NH), 13.75 (1Í, s, ÎÍ-5).
5-Hydroxy-4,7-dimethyl-6-[5-(2,3,4-trimethoxyphenyl)-4,5-dihydropyrazol-3-yl]-chromen-2-one (42). Yield
1
48%, mp 219–220ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.50 (3Í, s, ÑÍ -7), 2.62 (3Í,
23 24
2
6
6
3
s, ÑÍ -4), 3.13 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.75 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 3.78, 3.79 and 3.83 (9Í, three s, ÎÑÍ -2ꢃꢃ,
3
3
3ꢃꢃ, 4ꢃꢃ), 4.99 (1H, m, Í-5ꢃ), 6.14 (1Í, s, Í-3), 6.73 (1Í, s, Í-8), 6.82 (2Í, d, J = 8.8, H-5ꢃꢃ), 7.14 (2Í, d, J = 8.8, H-6ꢃꢃ), 7.65
(1H, d, J = 3.6, NH), 13.93 (1Í, s, ÎÍ-5).
5-Hydroxy-4,7-dimethyl-6-[5-(2,4,5-trimethoxyphenyl)-4,5-dihydropyrazol-3-yl]-chromen-2-one (43). Yield
1
54%, mp 227–228ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.49 (3Í, s, ÑÍ -7), 2.62 (3Í,
23 24
2
6
6
3
s, ÑÍ -4), 3.15 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.72 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 3.70 and 3.80 (9Í, two s, ÎÑÍ -2ꢃꢃ, 3ꢃꢃ,
3
3
4ꢃꢃ), 5.02 (1H, m, Í-5ꢃ), 6.14 (1Í, s, Í-3), 6.73 (2Í, s, Í-8, 3ꢃꢃ), 7.05 (1Í, s, H-6ꢃꢃ), 7.65 (1H, d, J = 3.6, NH), 13.89 (1Í, s,
ÎÍ-5).
5-Hydroxy-6-[5-(8-methoxy-1,4-benzodioxan-6-yl)-4,5-dihydropyrazol-3-yl]-4,7-dimethylchromen-2-one (44).
1
Yield 50%, mp 230–231ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 2.49 (3Í, s, ÑÍ -7), 2.61
23 22
2
6
6
3
(3Í, s, ÑÍ -4), 3.16 (1H, dd, J = 10.4, 16.4, Í-4ꢃà), 3.74 (1H, dd, J = 10.4, 16.4, Í-4ꢃb), 3.76 (3Í, s, ÎÑÍ -8ꢃꢃ), 4.21 (4Í, s,
3
3
ÑÍ -2ꢃꢃ, 3ꢃꢃ), 4.78 (1H, m, Í-5ꢃ), 6.13 (1Í, s, Í-3), 6.54 (2Í, s, H-5ꢃꢃ), 6.66 (2Í, s, H-7ꢃꢃ), 6.71 (1Í, s, Í-8), 7.77 (1H, d,
2
J = 3.6, NH), 13.92 (1Í, s, ÎÍ-5).
6-[5-(4-Chlorophenyl)-4,5-dihydropyrazol-3-yl]-4-ethyl-5-hydroxy-7-methylchromen-2-one (45). Yield 69%,
1
mp 223–224ꢁÑ, Ñ Í ClN Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.27 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.48
21 19
2
3
6
3
(3Í, s, ÑÍ -7), 3.05 (2Í, q, J = 7.2, ÑÍ -1ꢃ), 3.20–3.30 (1H, m, Í-4ꢃꢃa), 3.79 (1H, dd, J = 10.4, 16.4, Í-4ꢃꢃb), 4.87 (1H, m,
3
2
Í-5ꢃꢃ), 6.00 (1Í, s, Í-3), 6.63 (1Í, s, Í-8), 7.34 (2Í, d, J = 8.4, H-3ꢃꢃꢃ, 5ꢃꢃꢃ), 7.45 (2Í, d, J = 8.4, H-2ꢃꢃꢃ, 6ꢃꢃꢃ), 7.72 (1H, d,
J = 3.6, NH), 13.93 (1Í, s, ÎÍ-5).
833

4-Ethyl-5-hydroxy-6-[5-(4-methoxyphenyl)-4,5-dihydropyrazol-3-yl]-7-methylchromen-2-one (46). Yield 54%,
1
mp 221–222ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, CCl , ꢂ, ppm, J/Hz): 1.29 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.48 (3Í, s,
22 22
2
4
4
3
ÑÍ -7), 3.05 (2Í, q, J = 7.2, ÑÍ -1ꢃ), 3.20 (1H, dd, J = 10.0, 16.4, Í-4ꢃꢃa), 3.64 (1H, dd, J = 10.4, 16.4, Í-4ꢃꢃb), 3.78 (3Í, s,
3
2
ÎÑÍ -4ꢃꢃꢃ), 4.80 (1H, m, Í-5ꢃꢃ), 5.75 (1H, br.s, NH), 5.93 (1Í, s, Í-3), 6.54 (1Í, s, Í-8), 6.80 (2Í, d, J = 8.4, H-3ꢃꢃꢃ, 5ꢃꢃꢃ), 7.24
3
(2Í, d, J = 8.4, H-3ꢃꢃꢃ, 5ꢃꢃꢃ), 13.37 (1Í, s, ÎÍ-5).
6-[5-(4-Dimethylaminophenyl)-4,5-dihydropyrazol-3-yl]-5-hydroxy-7-methyl-4-propylchromen-2-one (47).
1
Yield 54%, mp 237–238ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.00 (3Í, t, J = 7.2,
24 27
3
3
6
ÑÍ -3ꢃ), 1.63 (2Í, m, ÑÍ -2ꢃ), 2.48 (3Í, s, ÑÍ -7), 2.88 (6Í, s, (CH ) N), 2.96 (2Í, m, ÑÍ -1ꢃ), 3.18 (1H, dd, J = 10.4, 16.4,
3
2
3
3 2
2
Í-4ꢃꢃà), 3.74 (1H, dd, J = 10.4, 16.4, Í-4ꢃꢃb), 4.75 (1H, m, Í-5ꢃꢃ), 6.11 (1Í, s, Í-3), 6.72 (2Í, d, J = 8.8, H-3ꢃꢃꢃ, 5ꢃꢃꢃ), 6.73 (1Í,
s, Í-8), 7.24 (2Í, d, J = 8.8, H-2ꢃꢃꢃ, 6ꢃꢃꢃ), 7.73 (1H, d, J = 3.6, NH), 14.05 (1Í, s, ÎÍ-5).
10-Ethyl-2-(4-methoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione 4-phenylhydrazone (48).
A mixture of 25 (0.73 g, 2 mmol) and phenylhydrazine (0.50 mL, 5 mmol) in EtOH (5 mL) was refluxed for 8 h (end of
reaction determined by TLC). The reaction mixture was cooled. The resulting precipitate was filtered off and crystallized
1
from EtOH. Yield 81%, mp 248–249ꢁÑ, Ñ Í N Î . H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.05 (3Í, t,
28 26
2
4
6
J = 7.2, ÑÍ -2ꢃ), 2.72–2.86 (3H, m, Í-3a, ÑÍ -1ꢃ), 2.83 (3Í, s, ÑÍ -5), 3.51 (1H, dd, J = 2.8, 17.6, Í-3b), 3.83 (3Í, s,
3
2
3
ÎÑÍ -4ꢃꢃ), 5.04 (1H, dd, J = 2.8, 12.4, Í-2), 6.01 (1Í, s, Í-9), 6.72 (1Í, t, J = 7.2, H-4ꢃꢃꢃ), 6.88 (1Í, s, Í-6), 6.97 (2Í, d,
3
J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 7.10–7.20 (4Í, m, H-2ꢃꢃꢃ, 3ꢃꢃꢃ, 5ꢃꢃꢃ, H-6ꢃꢃꢃ), 7.48 (2Í, d, J = 8.8, H-3ꢃꢃ, 5ꢃꢃ), 9.20 (1H, s, NH).
10-Ethyl-2-(4-methoxyphenyl)-5-methyl-2,3-dihydropyrano[2,3-f]chromen-4,8-dione 4-oxime (49). A mixture
of 25 (0.73 g, 2 mmol) and hydroxylamine hydrochloride (0.35 g, 5 mmol) in anhydrous Py (5 mL) was heated at 90–100°C
for 8 h (end of reaction determined by TLC). The reaction mixture was cooled, transferred into H O (100 mL), and acidified
2
to pH 6–7. The resulting precipitate was filtered off and crystallized from EtOH. Yield 72%, mp 203–204ꢁÑ, Ñ Í NÎ .
22 21
5
1
H NMR spectrum (400 MHz, DMSO-d , ꢂ, ppm, J/Hz): 1.03 (3Í, t, J = 7.2, ÑÍ -2ꢃ), 2.64 (3Í, s, ÑÍ -5), 2.72–2.86 (3H, m,
6
3
3
Í-3a, ÑÍ -1ꢃ), 3.42 (1H, dd, J = 3.2, 17.6, Í-3b), 3.81 (3Í, s, ÎÑÍ -4ꢃꢃ), 5.04 (1H, dd, J = 3.2, 12.4, Í-2), 6.01 (1Í, s, Í-9),
2
3
6.84 (1Í, s, Í-6), 6.93 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 7.41 (2Í, d, J = 8.4, H-3ꢃꢃ, 5ꢃꢃ), 11.23 (1H, s, NOH).
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