Synthesis of pyrano[2,3-f]chromen-2,8-diones and pyrano[3,2-g]chromen-2,8- diones based on o-hydroxyformyl(acyl)neoflavonoids

Article abstract of DOI:10.1007/s10600-008-0006-z

Novel pyrano[2,3-f]chromen-2,8-diones and pyrano[3,2-g]chromen-2,8-diones were prepared based on modified analogs of natural o-hydroxyformyl(acyl) neoflavonoids.

Full text of DOI:10.1007/s10600-008-0006-z

Chemistry of Natural Compounds, Vol. 44, No. 1, 2008
SYNTHESIS OF PYRANO[2,3- ]CHROMEN-2,8-DIONES AND
f
PYRANO[3,2- ]CHROMEN-2,8-DIONES BASED ON
g
-HYDROXYFORMYL(ACYL)NEOFLAVONOIDS
o
V. S. Moskvina and V. P. Khilya
UDC 547.814.5
Novel pyrano[2,3-f]chromen-2,8-diones and pyrano[3,2-g]chromen-2,8-diones were prepared based on
o
modified analogs of natural -hydroxyformyl(acyl)neoflavonoids.
Key words: Neoflavonoids, formylcoumarins, acylcoumarins, pyrano[2,3- ]chromen-2,8-diones, pyrano[3,2-
f
]chromen-2,8-diones.
g
Neoflavonoids of the 4-phenylcoumarin group that is widely distributed in nature [1] exhibit insecticidal and
antibacterial[2-5], antiatherosclerotic [6], anticonvulsive, antituberculosis, antimalarial[7], andcytotoxicactivity[8, 9]; inhibit
monophosphate adenosin-3′,5′-cyclase; act as anti-HIV agents [10]; inhibit proteinkinase activity; and are widely used as
antioxidants [11], pesticides, and bactericides.
We prepared starting 7-hydroxy-4-phenylcoumarins 1-4 via condensation of the corresponding phenols and
ethylbenzoylacetate in the presence of catalytic amounts of H SO . Neoflavonoids 1-3 were formylated in glacial acetic acid
2
4
by urotropine using the Duff reaction to give exclusively 7-hydroxy-8-formyl-4-phenylcoumarins 5, 6, and 7. The structures
of the -hydroxyformylcoumarins were proved by PMR spectroscopy. A weak-field singlet at 12.05-12.53 ppm for the 7-OH
o
group due to formation of an intramolecular H-bond and a resonance for the formyl group at 10.56-10.57 ppm were
characteristic.
H
O
O
O
HO
R
N
N
N
N
CH COOH
O
O
3
HO
R
5 - 7
CH
3
O
O
H C
3
O
O
O
O
O
R
HO
R
Ac O, Py
2
AlCl
3
1 - 3
11, 12
8, 9
1, 5:
2, 6, 8, 11:
3, 7, 9, 12:
R = Pr
R = H;
R = Et;
-Hydroxyacyl-4-phenylcoumarins 11-13 were prepared in two steps via acylation with acetic anhydride in pyridine
o
of the corresponding neoflavones 2-4 followed byFries rearrangement ofthe resulting acetoxycoumarins 8-10 using AlCl . The
3
Taras Shevchenko Kiev National University, 01033, Ukraine, Kiev, ul. Vladimirskaya, 64, e-mail:
v.moskvina@gmail.com. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 15-20, January-February, 2008. Original
article submitted July 26, 2007.
0009-3130/08/4401-0016 ©2008 Springer Science+Business Media, Inc.
16

PMR spectra of 11-13 exhibited a weak field singlet at 12.96-13.75 ppm for the OH group, which formed an intramolecular
H-bond with the o-acyl group.
CH
CH
3
CH
3
3
O
O
O
O
HO
H C
O
O
H C
3
O
HO
Ac O, Py
2
AlCl
3
3
O
O
4
10
13
The resulting formylated neoflavonoids were modified analogs of the recently observed scarce group of natural
formylcoumarins that includes voludala, a minor component of Dalbergia volubilic [12]; yunngnin A and B (isolated from
Hercaleum yunngningense roots [13]); sisafolin isolated from D. latifolia [14], and crenulatin, obtained from Hesperathusa
crenulata [15].
Acylated coumarins are more widelydistributed in nature. Examplesofsuch compoundsareracemosone, isolatedfrom
Mesua racemosa [16]; isodispar B, obtained from Calophyllum dispar and exhibiting cytotoxic activity [17];
acetylumbelliferone, from Daphne gnidiodes [18]; 7-hydroxy-6-acylcoumarin, isolated from Apium petroselinum [19]; and
8-acetyl-7-hydroxy-6-methoxychromen-2-one, obtained from Fraxinus floribunda [20].
Natural and synthetic analogs of o-hydroxyformyl(acyl)coumarins exhibit various pharmacological properties.
Formylcoumarins are typically antifungal [21] and antituberculosis agents [22]. Acylcoumarins have anti-inflammatory [23],
antimicrobial [24], antifungal [21], and antituberculosis [22] activities and act as inhibitors of arylhydrocarbonhydroxylase [25,
26].
Compounds 5-7 and 11-13 were next used as starting materials to prepare pyrano[2,3-f]chromen-2,8-diones
and pyrano[3,2-g]chromen-2,8-diones. Several methods are known for constructing this system.
Thus, using
o-hydroxyformyl(acyl)coumarins in Pechmann reaction [27] and reaction with acetylglycine [28],
a
ethoxycarbonylmethylenetriphenylphosphorane[29], and maleic acid (Pechmann reaction)[30], thecorrespondingpyrano[2,3-
f]chromen-2,8-diones were prepared. In our opinion, the most convenient method for preparing this system is condensation
of substituted acetophenons with phenylacetylchloride [31, 32].
R
1
CN
H
O
9
O
O
OEt
10
11
NC
8
O
HO
R
O
O
O
R
O
O
2
O
O
NC
R
1
O
6a
NaHCO
3
3
Pip, EtOH
4a
6'
R
5 - 7
14 - 22
23 - 25
NO
2
CH
3
NO
2
N
N
X =
Y =
Z =
S
S
14 - 16, 23: R = H, 17 - 19, 24: R = Et; 20 - 22, 25: R = Pr; 14, 17, 20: R1 = X; 15, 18, 21: R1 = Y; 16, 19, 21: R1 = Z
Reaction of formyl derivatives 5-7 with hetarylacetonitriles under mild conditions at room temperature in the presence
of piperidine as the base followed by acid hydrolysis produced the corresponding 2H,8H-pyrano[2,3-f]chromen-4-phenyl-9-
aryl(hetaryl)-2,8-diones 14-22.
The hydrolysis time ofthe intermediate iminocoumarins depended on the 9-aryl substituent. Thus, the hydrolysis time
for the 4-nitrophenyl substituent was about 1 h; for methyl- and phenylthiazolylcoumarins, 24-36 h. Hydrolysis of the imino
group was monitored using TLC. PMR spectra of 14-22 contained a characteristic singlet for the 10-H proton at weak field at
8.56-9.19 ppm.
17

TABLE 1. 13C NMR Spectra of 23 - 25
Compound
C atom
23
24
25
2
3
4
4a
5
6
6a
8
9
10
10a
11
1′
2′, 6′
3′, 5′
4′
160.8
112.7
155.4
116.9
126.4
118.2
149.7
156.6
100.1
119.5
123.9
145.8
142.0
126.7
128.7
128.0
115.8
-
160.8
112.7
155.4
116.8
125.3
129.6
148.7
156.6
100.0
119.8
123.8
143.0
140.0
126.4
128.7
128.0
115.8
27.2
160.8
112.7
155.4
117.0
125.7
128.2
149.1
156.6
100.3
119.7
124.0
143.1
141.0
126.5
128.7
128.0
115.8
33.0
CN
1′′
2′′
3′′
-
-
14.5
-
24.1
13.7
Reaction of formyl derivatives 5-7 with ethylcyanoacetate in the presence of NaHCO followed by acid hydrolysis
3
produced thecorresponding 2H,8H-pyrano[2,3-f]chromen-4-phenyl-9-carbonitriles23-25. PMRspectra oftheproductsshowed
13
a singlet at 8.89-9.1 ppm for the 10-H proton. A resonance at 116 ppm in the C NMR spectra corresponded to the 9-CN group
(Table 1).
3''
5''
Cl
O
CH
3
O
CH
3
1''
9
Cl
Cl
O
CH
10
3
Ph
Cl
HO
R
O
O
O
R
O
O
8
10a
O
O
11
O
O
O
2
6a
K CO ,
K CO ,
2 3
CH COCH
2
3
4a
3
6
CH COCH
R
3
3
3
3
4
5
1'
5'
3'
11, 12
28, 29
26, 27
26, 28:
27, 29:
R = Pr
R = Et;
CH
CH
3
3
CH
3
Cl
Cl
Ph
Cl
10a
4a
9a
O
O
O
O
HO
O
O
O
O
O
O
10
5
O
O
3
7
H C
3
5'
5a
K CO ,
2 3
CH COCH
K CO ,
Cl
2
3
1'
1''
CH COCH
3
3
CH
O
3
3
3
CH
3
3'
3''
5''
30
13
31
The reaction of aceylneoflavonoids 11-13 with phenylacetylchloride and chloroacetylchloride required more forcing
conditions than for formylneoflavonoids 5-7, i.e., boiling in acetone with K CO for 9-10 h, and formed the corresponding
2
3
pyrano[2,3-f]chromen-2,8-diones 26-29 with an angular structure and pyrano[3,2-g]chromen-2,8-diones 30-31 with a linear
structure.
18

TABLE 2. 13C NMR Spectra of 26 - 29
Compound
C atom
26
27
28
29
2
3
4
4a
5
6
6a
8
9
160.8
112.2
155.4
116.8
125.3
129.6
148.7
161.9
122.0
144.0
119.5
143.0
140.0
126.8
128.7
128.0
132.5
126.4
128.7
128.0
27.2
160.3
112.4
155.3
117.0
125.7
128.2
149.1
161.9
122.0
144.0
119.7
143.1
140.2
126.8
128.7
128.0
132.5
126.4
128.7
128.0
33.0
160.7
112.7
155.6
116.8
125.3
129.6
148.7
158.6
116.3
148.9
119.5
143.0
140.3
126.6
128.7
128.0
-
160.9
112.3
155.2
117.0
125.7
128.2
149.1
158.6
116.3
148.9
119.7
143.1
140.0
126.6
128.7
128.0
-
10
10a
11
1′
2′, 6′
3′, 5′
4′
1″
2″, 6″
3″, 5″
4″
1′″
2′″
3′″
10-CH3
-
-
-
-
-
-
27.2
14.5
-
33.0
24.1
13.7
12.0
14.5
-
14.5
24.1
13.7
14.5
12.0
TABLE 3. 13C NMR Spectra of 30 - 31
Compound
C atom
30
31
2
3
4
4a
5
5a
6
7
8
161.9
122.0
144.0
117.6
120.4
116.8
155.6
112.7
160.9
150.1
126.2
150.0
132.5
126.6
128.7
128.0
140.0
126.4
128.7
128.0
14.5
158.6
116.3
148.9
117.8
120.6
116.6
155.4
112.5
160.8
150.0
126.3
150.0
140.0
126.7
128.7
128.0
-
9a
10
10a
1′
2′,6′
3′,5′
4′
1″
2″,6″
3″,5″
4″
4-CH3
10-CH3
-
-
-
12.0
13.3
13.1
19

13
The structures of 26-31 were proved using PMR and C NMR spectroscopy. Thus, PMR spectra lacked resonances
13
for the 7-OHgroup. C NMRspectra (Tables 2 and 3) of26-31 contained characteristic resonances for carbonyls ofthe pyrano-
2-one moieties at 158.6-162 ppm.
EXPERIMENTAL
The course of reactions and purity of products were monitored by TLC on Merck F254 plates with elution by
CHCl :CH OH (9:1 and 95:5). Melting points were measured on a Kofler block. PMR spectra in DMSO-d and trifluoroacetic
3
3
6
1
13
acid (TFA) were recorded on a Mercury-400 spectrometer (400 MHz for H and 100 MHz for C) relative to TMS (internal
standard). Elemental analyses of all compounds agreed with those calculated.
Hydroxycoumarins 1, 2, 3, and 4 were prepared as before [33]. Melting points and PMR spectra agreed with those in
the literature.
General Method for Formylation of 7-Hydroxyneoflavonoids. A solution of the appropriate 7-hydroxyneoflavone
(5 mmol) and hexamethylenetetramine (7 g, 50 mmol) in acetic acid (20 mL) was heated on a water bath for 6-8 h, poured into
HCl (24 mL, 17%), boiled for 10 min, and treated with water (40 mL). The resulting solid was filtered off after several hours
and crystallized from ethanol.
7-Hydroxy-2-oxo-4-phenyl-2H-chromen-8-carbaldehyde (5). Yield 0.8 g (60.15%), C H O , mp 120°C.
16 10
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.24 (1H, s, H-3), 6.85 (1H, d, J = 9.2, H-6), 7.47 (2H , m, H-2′,
6
H-6′), 7.53 (3H, m, H-3′, H-4′, H-5′), 7.61 (1H, d, J = 9.2, H-5), 10.57 (1H, s, 8-CHO), 12.05 (1H, s, 7-OH).
6-Ethyl-7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-carbaldehyde (6). Yield 0.67 g (50.75%), C H O , mp 138-
18 14
4
140°C.
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.12 (3H, m, CH CH -6), 2.53 (2H, t, J = 6.4, CH CH -6), 6.22
6
3
2
3
2
(1H, s, H-3), 7.2 (1H, s, H-5), 7.47 (2H, m, H-2′, H-6′), 7.54 (3H, m, H-3′, H-4′, H-5′), 10.57 (1H, s, 8-CHO), 12.53 (1H, s,
7-OH).
7-Hydroxy-2-oxo-4-phenyl-6-propyl-2H-chromen-8-carbaldehyde (7). Yield 0.61 g (43.8%), C H O , mp 136-
19 16
4
137°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.91 (3H, m, CH CH CH -6), 1.52 (2H, m, CH CH CH -6), 2.47
6
3
2
2
3
2
2
(2H, t, J = 7.6, CH CH CH -6), 6.21 (1H, s, H-3), 7.07 (1H, s, H-5), 7.49 (2H, m, H-2′, H-6′), 7.58 (3H, m, H-3′, H-4′, H-5′),
3
2
2
10.56 (1H, s, 8-CHO), 12.53 (1H, s, 7-OH).
General Method for Acylation of 7-Hydroxyneoflavonoids. A suspension of the appropriate 7-hydroxyneoflavone
(15 mmol) in acetic anhydride (30 mmol) was heated with a catalytic amount of pyridine (2-3 drops) until totallydissolved, left
at room temperature until a precipitate formed, poured into icewater (200 mL), and filtered. The solid was crystalized from
methanol.
6-Ethyl-7-acetoxy-4-phenylchromen-2-one (8). Yield 3.2 g (80.2%), C H O , mp 152-154°C.
19 16
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.11 (3H, m, CH CH -6), 2.35 (3H, s, CH COO-7), 2.52 (2H,
6
3
2
3
t, J = 6.4, CH CH -6), 6.28 (1H, s, H-3), 7.22 (1H, s, H-5), 7.32 (1H, s, H-8), 7.51 (2H, m, H-2′, H-6′), 7.56 (3H, m, H-3′, H-4′,
3
2
H-5′).
7-Acetoxy-4-phenyl-6-propylchromen-2-one (9). Yield 4.6 g (95.13%), C H O , mp 128-129°C.
20 18
4
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.91 (3H, m, CH CH CH -6), 1.51(2H, m, CH CH CH -6), 2.35
6
3
2
2
3
2
2
(3H, s, CH COO-7), 2.45 (2H, t, J = 7.6, CH CH CH -6), 6.29 (1H, s, H-3), 7.23 (1H, s, H-5), 7.31 (1H, s, H-8), 7.51 (2H, m,
3
3
2
2
H-2′, H-6′), 7.56 (3H, m, H-3′, H-4′, H-5′).
7-Acetoxy-8-methyl-4-phenylchromen-2-one (10). Yield 3.98 g (90.15%), C H O , mp 189-190°C (lit. [34]
18 14
4
mp 140°C, [35] 188-188.5°C).
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.28 (3H, s, CH -8), 2.36 (3H, s, CH COO-7), 6.31 (1H, s, H-3),
6
3
3
7.01 (1H, d, J = 8.8, H-6), 7.33 (1H, d, J = 8.4, H-5), 7.49 (2H, m, H-2′, H-6′), 7.55 (3H, m, H-3′, H-4′, H-5′).
General Method for Preparing o-Hydroxyacylcoumarins. A mixture of the appropriate 7-acetoxyneoflavone
(15 mmol) and AlCl (75 mmol) was heated at 120°C with vigorous stirring for 1 h, cooled, and mixed with HCl (100 mL,
3
1 N). The resulting precipitate was filtered off and crystallized from propan-2-ol.
8-Acetyl-6-ethyl-7-hydroxy-4-phenylchromen-2-one (11). Yield 2.7 g (67.66%), C H O , mp 144-145°C.
19 16
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.11 (3H, m, CH CH -6), 2.59 (2H, t, J = 7.2, CH CH -6), 2.93
6
3
2
3
2
20

(3H, s, CH CO-8), 6.18 (1H, s, H-3), 7.36 (1H, s, H-5), 7.44 (2H, m, H-2′, H-6′), 7.56 (3H, m, H-3′, H-4′, H-5′), 13.74 (1H, s,
3
OH-7).
8-Acetyl-7-hydroxy-4-phenyl-6-propylchromen-2-one (12). Yield 3.9 g (80.74%), C H O , mp 187-188°C.
20 18
4
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.91 (3H, m, CH CH CH -6), 1.52 (2H, m, CH CH CH -6), 2.45
6
3
2
2
3
2
2
(2H, t, J = 7.6, CH CH CH -6), 2.92 (3H, s, CH CO-8), 6.18 (1H, s, H-3), 7.33 (1H, s, H-5), 7.43 (2H, m, H-2′, H-6′), 7.55 (3H,
3
2
2
3
m, H-3′, H-4′, H-5′), 13.75 (1H, s, OH-7).
6-Acetyl-7-hydroxy-8-methyl-4-phenylchromen-2-one (13). Yield 3.26 g (73.9%), C H O , mp 201-202°C (lit.
18 14
4
[36] mp 203°C).
PMR spectrum (400 MHz, DMSO-d , δ, ppm): 2.27 (3H, s, CH -8), 2.46 (3H, s, CH COO-7), 6.21 (1H, s, H-3), 7.50
6
3
3
(5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.82 (1H, s, H-5), 12.95 (1H, s, OH-7).
General Method for Preparing 14-22.
A solution of the appropriate 7-hydroxy-8-formylneoflavone (1 mmol) and the corresponding aryl(hetaryl)acetonitrile
(1 mmol) in ethanol was treated with several drops of piperidine and left at room temperature for 24 h. The resulting
precipitated iminocoumarin was mixed with aqueous H SO (5%) and heated on a water bath for 1-36 h. The course of the
2
4
reaction was monitored by TLC. When the reaction was finished, the precipitate was filtered off and crystallized from ethanol.
9-(4-Nitrophenyl)-4-phenylpyrano[2,3-f]chromen-2,8-dione (14). Yield0.16g(38.9%), C H O , mp249-250°C.
24 13
6
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.42 (1H, s, H-3), 7.34 (1H, d, J = 9.2, H-6), 7.56 (5H, m, H-2′,
6
H-3′, H-4′, H-5′, H-6′), 7.70 (1H, d, J = 8.8, H-5), 8.09 (2H, d, J = 8.8, H-3″, H-5″), 8.31 (2H, d, J = 8.8, H-2″, H-6″), 8.56 (1H,
s, H-10).
9-[4-(3-Nitrophenyl)thiazol-2-yl]-4-phenylpyrano[2,3-f]chromen-2,8-dione (15).
C H N O S, mp 332-333°C.
Yield 0.25 g (50.6%),
27 14
2 6
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 6.85 (1H, s, H-3), 7.57 (H-6, d, J = 8.4, H-6), 7.61 (5H, m, H-2′, H-3′,
H-4′, H-5′, H-6′), 7.66 (1H, d, J = 8.4, H-5), 7.96 (1H, t, J = 8, H-5′″), 8.28 (1H, s, H-2′″), 8.30 (1H, d, J = 8, H-6′″), 8.48 (1H,
s, H-3″), 8.62 (1H, d, J = 8, H-4′″), 8.85 (1H, s, H-10).
9-(4-Methylthiazol-2-yl)-4-phenylpyrano[2,3-f]chromen-2,8-dione (16). Yield 0.09 g (23.3%), C H NO S,
22 13
4
mp 263-264°C.
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 2.87 (3H, s, CH -4 ), 6.86 (1H, s, H-3), 7.62 (1H, d, J = 9.2, H-6), 7.69
3
(5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.83 (1H, s, H-3″), 8.28 (1H, d, J = 9.2, H-5), 9.19 (1H, s, H-10).
6-Ethyl-9-(4-nitrophenyl)-4-phenylpyrano[2,3-f]chromen-2,8-dione (17). Yield 0.12 g (23.7%), C H NO ,
26 17
6
mp 286-287°C.
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.11 (3H, m, CH CH -6), 2.59 (2H, t, J = 7.2, CH CH -6), 6.41
6
3
2
3
2
(1H, s, H-3), 7.45 (1H, s, H-5), 7.57 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 8.10 (2H, d, J = 8.8, H-3″, H-5″), 8.32 (2H, d, J = 8.8,
H-2″, H-6″), 8.57 (1H, s, H-10).
6-Ethyl-9-[4-(3-nitrophenyl)thiazol-2-yl]-4-phenylpyrano[2,3-f]chromen-2,8-dione (18). Yield 0.15 g (28.7%),
C H N O S, mp 239-240°C.
29 18
2 6
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 1.09 (3H, m, CH CH -6), 2.57 (2H, t, J = 7.2, CH CH -6), 6.83 (1H,
3
2
3
2
s, H-3), 7.62 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.66 (1H, s, H-5), 7.94 (1H, t, J = 8, H-5′″), 8.29 (1H, s, H-2′″), 8.31 (1H,
d, J = 8, H-6′″), 8.46 (1H, s, H-3″), 8.62 (1H, d, J = 8, H-4′″), 8.86 (1H, s, H-10).
6-Ethyl-9-(4-methylthiazol-2-yl)-4-phenylpyrano[2,3-f]chromen-2,8-dione (19).
C H NO S, mp 289-290°C.
Yield 0.11 g (26.5%),
24 17
4
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 1.23 (3H, m, CH CH -6), 2.69 (2H, t, J = 7.2, CH CH -6), 2.83 (3H,
3
2
3
2
s, CH -4″), 6.82 (1H, s, H-3), 7.65 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.80 (1H, s, H-3″), 8.14 (1H, s, H-5), 9.12 (1H, s, H-10).
3
9-(4-Nitrophenyl)-4-phenyl-6-propionylpyrano[2,3-f]chromen-2,8-dione (20). Yield 0.1 g (22.7%), C H NO ,
27 19
6
mp 272-273°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.91(3H, m, CH CH CH -6), 1.52 (2H, m, CH CH CH -6), 2.45
6
3
2
2
3
2
2
(2H, t, J = 7.6, CH CH CH -6), 6.39 (1H, s, H-3), 7.43 (1H, s, H-5), 7.56 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 8.08 (2H, d,
3
2
2
J = 8.8, H-3″, H-5″), 8.31 (2H, d, J = 8.8, H-2″, H-6″), 8.56 (1H, s, H-10).
9-[4-(3-Nitrophenyl)thiazol-2-yl]-4-phenyl-6-propylpyrano[2,3-f]chromen-2,8-dione (21). Yield0.19g, (35.4%),
C H N O S, mp 246-247°C.
30 20
2 6
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 0.93 (3H, m, CH CH CH -6), 1.54 (2H, m, CH CH CH -6), 2.48 (2H,
3
2
2
3
2
2
21

t, J = 7.6, CH CH CH -6), 6.81 (1H, s, H-3), 7.63 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.64 (1H, s, H-5), 7.96 (1H, t, J = 8,
3
2
2
H-5′″), 8.27 (1H, s, H-2′″), 8.30 (1H, d, J = 8, H-6′″), 8.43 (1H, s, H-3′″), 8.61 (1H, d, J = 8, H-4′″), 8.84 (1H, s, H-10).
9-(4-Methylthiazol-2-yl)-4-phenyl-6-propylpyrano[2,3-f]chromen-2,8-dione (22). Yield 0.07 g (16.3%),
C H NO S, mp 207-208°C.
25 19
4
PMR spectrum (400 MHz, TFA, δ, ppm, J/Hz): 0.96 (3H, m, CH CH CH -6), 1.67 (2H, m, CH CH CH -6), 2.76 (2H,
3
2
2
3
2
2
t, J = 7.6, CH CH CH -6), 2.88 (3H, s, CH -4″), 6.65 (1H, s, H-3), 7.39 (1H, s, H-5), 7.58 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′),
3
2
2
3
7.73 (1H, s, H-3″), 9.19 (1H, s, H-10).
General Method for Preparing 23-25. The appropriate 7-hydroxy-8-formylneoflavone (1 mmol) and
ethylcyanoacetate (1 mmol) in alcoholic NaHCO (0.05 M) was stirred at room temperature for 3 h, diluted with HCl (0.25 mL),
3
heated for 2 h at 70°C, and cooled. The precipitate was filtered off and crystallized from propan-2-ol.
2,8-Dioxo-4-phenyl-2H,8H-pyrano[2,3-f]chromen-9-carbonitrile(23). Yield0.15g(47.6%),C H NO , mp296°C.
19
9
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.42 (1H, s, H-3), 7.30 (1H, d, J = 8.8, H-6), 7.52 (5H, m, H-2′,
6
H-3′, H-4′, H-5′, H-6′), 7.75 (1H, d, J = 8.8, H-5), 8.89 (1H, s, H-10).
6-Ethyl-2,8-dioxo-4-phenyl-2H,8H-pyrano[2,3-f]chromen-9-carbonitrile(24). Yield0.13g(37.9%), C H NO ,
21 13
4
mp 282-283°C.
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.09 (3H, m, CH CH -6), 2.56 (2H, t, J = 7.2, CH CH -6), 6.41
6
3
2
3
2
(1H, s, H-3), 7.32 (1H, d, J = 8.8, H-6), 7.54 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.74 (1H, d, J = 8.8, H-5), 8.87 (1H, s, H-10).
2,8-Dioxo-4-phenyl-6-propyl-2H,8H-pyrano[2,3-f]chromen-9-carbonitrile(25). Yield0.17g(47.6%), C H NO ,
22 15
4
mp 267-268°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.91 (3H, m, CH CH CH -6), 1.52 (2H, m, CH CH CH -6), 2.45
6
3
2
2
3
2
2
(2H, t, J = 7.6, CH CH CH -6), 6.42 (1H, s, H-3), 7.31 (1H, d, J = 8.8, H-6), 7.51 (5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.72
3
2
2
(1H, d, J = 8.8, H-5), 8.88 (1H, s, H-10).
General Method for Preparing 26-31. A mixture of hydroxyacylneoflavone 11, 12, or 13 (1 mmol),
phenylacetylchloride or chloroacetylchloride (2 mmol), and freshly calcined K CO (4 mmol) in absolute acetone (20 mL) was
2
3
stirred at boiling for 6-9 h. The course of the reaction was monitored by TLC. After the reaction was finished the solvent was
evaporated in vacuo in a rotary evaporator. The solid was treated with water. The resulting solid was filtered off, washed with
water, and crystallized from aqueous methanol.
6-Ethyl-10-methyl-4,9-diphenylpyrano[2,3-f]chromen-2,8-dione (26). Yield 0.15 g (36.8%), C H O , mp 232-
27 20
4
234°C.
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.24 (3H, m, CH CH -6), 2.67 (3H, s, CH -10), 2.82 (2H, t,
6
3
2
3
J = 7.2, CH CH -6), 6.35 (1H, s, H-3), 7.30 (2H, m, H-2″, H-6″), 7.44 (3H, m, H-3″, H-4″, H-5″), 7.46 (1H, s, H-5), 7.49 (2H,
3
2
m, H-2′, H-6′), 7.59 (3H, m, H-3′, H-4′, H-5′).
10-Methyl-4,9-diphenyl-6-propylpyrano[2,3-f]chromen-2,8-dione (27). Yield 0.18g(42.7%), C H O , mp 238-
28 22
4
239°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.98 (3H, m, CH CH CH -6), 1.65 (2H, m, CH CH CH -6), 2.66
6
3
2
2
3
2
2
(3H, s, CH -10), 2.76 (2H, t, J = 7.6, CH CH CH -6), 6.35 (1H, s, H-3), 7.29 (2H, m, H-2″, H-6″), 7.44 (3H, m, H-3″, H-4″,
3
3
2
2
H-5″), 7.46 (1H, s, H-5), 7.49 (2H, m, H-2′, H-6′), 7.59 (3H, m, H-3′, H-4′, H-5′).
9-Chloro-6-ethyl-10-methyl-4-phenylpyrano[2,3-f]chromen-2,8-dione (28). Yield 0.12 g (32.8%), C H ClO ,
21 15
4
mp 137-138°C.
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.12 (3H, m, CH CH -6), 2.62 (2H, t, J = 7.2, CH CH -6), 2.98
6
3
2
3
2
(3H, s, CH -10), 6.16 (1H, s, H-3), 7.38 (1H, s, H-5), 7.47 (2H, m, H-2′, H-6′), 7.56 (3H, m, H-3′, H-4′, H-5′).
3
9-Chloro-10-methyl-4-phenyl-6-propylpyrano[2,3-f]chromen-2,8-dione (29). Yield 0.14 g (36.8%), C H ClO ,
22 17
4
mp 142-143°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 0.89 (3H, m, CH CH CH -6), 1.52 (2H, m, CH CH CH -6), 2.53
6
3
2
2
3
2
2
(2H, t, J = 7.6, CH CH CH -6), 2.93 (3H, s, CH -10), 6.18 (1H, s, H-3), 7.33 (1H, s, H-5), 7.45 (2H, m, H-2′, H-6′), 7.55 (3H,
3
2
2
3
m, H-3′, H-4′, H-5′).
4,10-Dimethyl-3,6-diphenylpyrano[3,2-g]chromen-2,8-dione (30). Yield0.18g(45.7%), C H O , mp285-286°C.
26 18
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm): 2.15 (3H, s, CH -4), 2.52 (3H, s, CH -10), 6.38 (1H, s, H-7), 7.25 (2H,
6
3
3
m, H-2′, H-6′), 7.43 (3H, m, H-3′, H-4′, H-5′), 7.56 (5H, m, H-2″, H-3″, H-4″, H-5″, H-6″), 7.66 (1H, s, H-5).
22

3-Chloro-4,10-dimethyl-6-phenylpyrano[3,2-g]chromen-2,8-dione (31). Yield 0.16 g (45.4%), C H ClO ,
20 13
4
mp 207-208°C.
PMRspectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.28 (3H, s, CH -4), 2.52 (3H, s, CH -10), 6.20 (1H, s, H-7), 7.55
6
3
3
(5H, m, H-2′, H-3′, H-4′, H-5′, H-6′), 7.81 (1H, s, H-5).
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