Synthesis and NMR spectroscopy investigations of functionalized 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]chromene-2,6-diones and their spirothiadiazole derivatives

Article abstract of DOI:10.1007/s00706-008-0934-0

New functionalized derivatives of 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H, 6H-pyrano[3,2-g]-chromene-2,6-dione - analogues of the natural compound graveolone - possessing hydrazine, hydroxylamine, and thiosemicarbazide residues were synthesized and their

Full text of DOI:10.1007/s00706-008-0934-0

Monatsh Chem 139, 1391–1396 (2008)
DOI 10.1007/s00706-008-0934-0
Printed in The Netherlands
Synthesis and NMR spectroscopy investigations of functionalized 8,8,10-
trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]chromene-2,6-diones
and their spirothiadiazole derivatives
Viktoria S. Moskvina1, Olexander V. Turov1, Volodymyr P. Khilya1, Myroslav M. Garazd2,
Ulrich M. Groth3
1
Chemistry Department, Kyiv National Taras Shevchenko University, Kyiv, Ukraine
2
National Academy of Sciences of Ukraine, Institute of Bioorganic Chemistry and Petroleum Chemistry,
Kyiv, Ukraine
3
Faculty of Chemistry, Konstanz University, Konstanz, Germany
Received 5 March 2008; Accepted 25 March 2008; Published online 9 June 2008
# Springer-Verlag 2008
Abstract New functionalized derivatives of 8,8,10-
trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]-
chromene-2,6-dione – analogues of the natural
compound graveolone – possessing hydrazine, hy-
droxylamine, and thiosemicarbazide residues were
synthesized and their reactions with acetic anhydride
were studied. The structure of the obtained com-
pounds was confirmed by NMR spectroscopy.
activities, and possess HIV-1 reverse transcriptase
inhibition properties. At the same time, neoflavones
are suitable targets for chemical modification [8].
Their synthetic derivatives show antioxidant [9],
antiatheroscletoric [10], cytotoxic [11], and antibac-
terial [12, 13] properties. Also, it is rather common
for natural neoflavones to contain a pyran or furan
ring annulated with the benzopyran-2-one system.
This work is devoted to the synthesis of such
natural compounds through modification of dihy-
dro-2H,6H-pyrano[3,2-g]chromene-2,6-dione at the
exocyclic oxygen atom, which leads to the formation
of nitrogen-containing derivatives functionalized at
position 6.
Keywords Heterocycles; Natural products; NMR spectros-
copy; Neoflavones; 8,8,10-Trimethyl-4-phenyl-7,8-dihydro-
2H,6H-pyrano[3,2-g]chromene-2,6-dione.
Introduction
Derivatives of 4-phenyl-2H-chromen-2-ones, or neo-
flavones, are widespread in nature. By today, more
than 130 corresponding compounds have been ex-
tracted from natural sources [1]. These neoflavones
exhibit bactericidal [2], insecticidal [3], hypoglyce-
mic [4], antitumor [5], antimalarial [6], cytotoxic [7]
Results and discussion
The starting linear 8,8,10-trimethyl-4-phenyl-7,8-
dihydro-2H,6H-pyrano[3,2-g]chromene-2,6-dione
(1, Fig. 1) – a modified analogue of graveolone
(Formulae) – was synthesized by Kabbe cyclization
of 6-acetyl-7-hydroxy-8-methyl-4-phenyl-2H-chro-
mene-2-one with acetone in the presence of pyrroli-
dine, which resulted in the 2,2-dimethylpyranone
ring formation [14, 15].
Correspondence: Viktoria Moskvina, Chemistry Department,
Kyiv National Taras Shevchenko University, 60, ul.
Vladimirskaya, 01033 Kyiv, Ukraine. E-mail: v.moskvina@
gmail.com

1392
V. S. Moskvina et al.
Scheme 1
Fig. 1 8,8,10-Trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyra-
no[3,2-g]chromene-2,6-dione and its numbering scheme
Further treatment of dihydropyrano[3,2-g]chro-
mene-2,6-dione 1 with several nucleophilic re-
agents, such as hydrazine hydrate, hydroxylamine,
thiosemicarbazide, N-methylthiosemicarbazide, and
N-phenylthiosemicarbazide led to 8,8,10-trimethyl-
4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]chromene-
2,6-dione 6-hydrazone (2), 6-oxime (3), 6-thiosemi-
carbazone (4), 6-(N-methylthiosemicarbazone) (5)
and 6-(N-phenylthiosemicarbazone) (6) (Scheme 1).
Only the exocyclic oxygen atom of the 2,2-dimethyl-
2,3-dihydropyran-4-one ring, and not the oxygen at-
om of the benzopyran-2-one ring, was attacked by
Scheme 2
the nucleophiles, even when a three-fold excess of
the latter was used.
Subsequent acylation of 2–6 led to N- and O-acyl
derivatives of hydrazone 2 and oxime 3 – N0-[8,8,10-
trimethyl-2-oxo-4-phenyl-7,8-dihydro-2H,6H-pyrano-
Table 1 1H chemical shifts (ꢀ=ppm) of 2–11 in DMSO-d6
b
c
No. H-3a H-5a 7-CH2 8-CH3 (ꢀ2)a 10-CH3 H-20, 60 H-30, 40, 50 Other signals
a
2
3
4
5
6
6.04 7.69
6.12 7.73
6.17 7.95
6.19 7.97
6.18 8.17
2.50a
2.77a
2.90a
2.89a
2.93a
1.42
1.38
1.39
1.39
1.42
2.29
2.26
2.26
2.26
2.28
7.39
7.45
7.51
7.46
7.43
7.44
7.54
7.54
7.56
7.58
5.07 (wide s, 6-NNH2)
11.16 (s, 6-NOH)
7.05 (s, NH), 8.18 (s, NH), 10.44 (s, NH)
3.01 (s, N-CH3), 7.74 (s, NH), 10.50 (s, NH)
6.74 (H-200,400,600), 7.17 (m, H-300,H-500),
9.76 (s, NH), 10.76 (s, NH)
10.47 (s, NH), 2.01 (s, NAc)
2.15 (s, NOAc)
2.07 (s, AcN-TDA), 1.99 (s, AcNH-TDA),
11.66 (s, NH)
1.89 (s, AcN-TDA), 2.26
7
8
9
6.17 7.93
6.19 7.89
6.23 7.26
2.75a
2.96a
1.40
1.43
2.27
2.28
2.19
7.51
7.49
7.39
7.56
7.56
7.53
2.51d,
3.25e,f
2.54d,
3.34e,f
2.85d,
3.15e,f
1.31e,
1.47d
1.39e,
1.48d
1.42e,
1.48d
10
11
6.19 7.32
6.18 7.28
2.10
2.11
7.47
7.42
7.56
7.59
(s, AcNCH3-TDA), 3.01 (s, AcNCH3-TDA)
1.86 (s, AcN-TDA), 2.24 (s, AcNPh), 7.17,
6.79 (m, AcNPh)
a
b
c
d
e
f
s.; d., J ¼ 8.8 Hz; m.; pro-S; pro-R; 2ꢀd., J ¼ 14.0 Hz

Functionalized 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]chromene-2,6-diones
1393
[3,2-g]chromen-6-ylidene]acetohydrazide (7) and
8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-py-
rano[3,2-g]chromene-2,6-dione 6-(O-acetyloxime)
(8); in case of thiosemicarbazides 4–6 cyclization
of the thiosemicarbazide residue into the 1,3,4-thia-
diazoline ring occurred, leading to the formation of
the corresponding N-[30-acetyl-2,2,10-trimethyl-8-
oxo-6-phenyl-2,3-dihydro-30H,8H-spiro[pyrano[3,2-
g]chromene-4,20-[1,3,4]thiadiazol]-50-yl]acetamide
(9), -N-methylacetamide (10), and -N-phenylacet-
amide (11) (Scheme 2).
The 13C NMR absorption of C-6 in compounds
2–8 occurs at 136.1–151.4 ppm, whereas it is
observed at ꢀ ¼ 74.7–76.9 ppm for 9–11. For com-
parison, the chemical shift of the C-6 in dihydro-
pyrano[3,2-g]-chromene-2,6-dione 1 is 196.8 ppm.
The substitution affects not only the C-6 atom, but
more distant atoms as well. For example, the C-7
signal of compound 1 is observed at 49.5 ppm and,
upon the substitution of the oxygen atom at C-6
with nitrogen atom in hydrazone 2, oxime 3 and
thiosemicarbazides 4–6, experiences an upfield shift
(31.7–33.8 ppm). A lesser effect of the substituent at
C-6 on the chemical shift of C-8 is also observed. 1H
and 13C NMR signals of other atoms of molecules
1H and 13C NMR data confirmed the structures
1
of 2–11. H NMR spectra (Table 1) of 2–11 corre-
sponded to the proposed structures; however, since
the skeleton of the molecules is complex and lactone
derivatives are known to be unstable in the presence
of nucleophilic reagents, 13C NMR spectra were
measured to prove the structure of the compounds
(Table 2).
1
2–6 are insensitive to changes at C-6. The H and
13C NMR peaks in the spectra of acyl derivatives
of hydrazone and oxime (7 and 8) can be reliably
assigned; in the case of 9–11 a more detailed discus-
sion is required.
Table 2 13C chemical shifts (ꢀ=ppm) of 1–11 in DMSO-d6
No.
C-2
C-3
C-4
C-4a
C-5
C-5a
C-6
C-7
C-8
C-9a
1
2
3
4
5
6
7
8
160.8
159.9
159.6
160.8
159.9
159.9
160.8
160.8
160.4
160.8
160.8
112.7
112.4
112.5
112.7
112.6
112.7
112.7
112.5
112.4
112.7
112.7
155.4
154.5
155.8
155.3
155.4
155.3
155.4
155.4
155.3
155.4
155.4
111.6
111.8
112.1
111.9
111.8
111.6
111.8
111.6
112.9
111.5
111.5
123.2
128.5
128.5
126.9
127.6
126.9
123.6
123.8
123.4
123.7
123.7
116.9
113.5
113.9
113.7
113.9
112.9
113.9
113.7
122.7
121.7
121.7
196.8
136.1
146.1
146.5
146.5
145.8
146.5
151.4
74.7
49.5
33.8
33.4
31.7
31.7
32.9
30.1
34.2
44.8
45.6
44.6
78.3
96.1
96.1
94.8
96.1
95.8
96.3
97.3
77.1
68.0
75.4
156.4
156.1
155.1
156.3
156.8
155.4
156.8
156.8
154.2
153.2
153.2
9
10
11
76.8
76.9
No. C-10 C-10a 8-CH3 (ꢀ2) 10-CH3 C-10 C-20,60 C-30,50 C-40 Other signals
1
2
3
4
5
6
119.0 155.4
118.5 152.5
119.1 153.5
119.2 152.8
119.2 153.4
119.1 153.3
26.7
27.3
27.1
27.3
27.1
27.3
8.6
8.4
9.6
9.8
9.6
9.8
140.0 126.4
128.2 129.5
129.1 129.7
130.3 128.9
127.9 129.7
128.7 129.6
128.7 128.0
116.3 128.9
115.1 128.3
–
–
–
116.5 128.6 181.4 (C¼S)
115.6 128.0 176.8 (C¼S), 34.3 (NH–CH3)
115.4 127.8 178.0 (C¼S), 137.6, 126.3, 129.3, 123.9
(NH–Ph)
7
8
9
119.2 153.3
119.1 153.6
113.4 152.7
27.0
27.7
10.2
9.6
8.9
134.2 126.4
136.1 126.4
135.6 129.1
123.9 128.3 25.3, 173.4 (6-NNH-Ac)
125.3 128.4 18.3, 168.3 (6-NO-Ac)
129.6 130.6 23.0, 168.2 (Ac), 22.7, 171.5 (AcNH),
143.6 (TDA-C-5)
128.7 130.1 23.0, 168.2 (Ac), 20.2, 173.0 (AcNCH3),
26.2 (AcNCH3), 145.8 (TDA-C-5)
128.7 128.0 23.0, 168.2 (Ac), 20.1, 174.1 (AcNPh),
121.6, 124.4, 129.0, 135.3, (AcNPh),
148.3 (TDA-C-5)
25.8a,
30.3b
24.6a,
29.4b
26.3a,
31.0b
10
11
115.6 148.2
118.9 148.2
9.4
9.2
136.3 126.4
140.0 126.4
a
b
pro-R; pro-S

1394
V. S. Moskvina et al.
The NMR spectra of 9–11 correspond to their
(HMBC) experiments. Table 3 summarizes the coor-
dinates of cross-peaks observed in HMQC and HMBC
spectra of corresponding compounds
expected structures, but an unequivocal assignment
of all signals cannot be done using 1H and 13C NMR
spectra data alone. The assignment becomes possible
A more detailed explanation of the spectra of 9 is
provided to clarify the obtained results. Two singlets
with chemical shifts of 7.26 and 6.23 ppm (which
corresponds to aromatic protons absorption region)
1
only be means of two-dimensional H–13C shift
correlation via one bond (HMQC) and long-range
1
are observed in the H NMR spectra; these two
Table 3 Heteronuclear correlation data for 9–11
signals are assigned to H-5 and H-3 protons. The
H-3 signal correlates with a low-field 13C NMR sig-
nal at ꢀ ¼ 160.4 ppm. This allows to assign this sig-
nal to the C-2 atom, which is separated from the H-3
by two chemical bonds. The presence of H-3–H-30
correlation signals with a 13C signal at 135.6 ppm
lets us to assign the latter signal to the C-10 atom.
The assignment of a 13C NMR signal at 155.3 ppm
to the C-4 follows from its correlations with H-20 and
H-5 proton signals. The nodal C-9a and C-10a atoms
can be assigned based on correlations of their signals
with C-10 methyl proton signals; the correlations
also identify the 13C signal of the mentioned methyl
group. Signals of methyl residues of N-acetyl groups
are assigned from their correlations with correspond-
ing carbonyl C atoms. Bearing in mind that the signal
of the NH-proton correlates with a 13C NMR signal of
one of the carbonyls (at 171.5 ppm), all the signals of
acetyl fragments may be reliably assigned. A scheme
which shows the assignments and the most important
HMBC correlations upon which the assignments were
based is shown in (Fig. 2).
No. 1H NMR 13C NMR signals which correlate
1
with H NMR signal, ꢀ=ppm
signal,
ꢀ=ppm
HMQC
HMBC
9
1.31
1.47
25.8
30.3
30.3, 44.8, 77.1
25.8, 44.8, 74.7, 77.1,
154.2
1.99
2.07
2.19
2.51
3.25
6.23
7.26
22.7
23.0
8.9
44.8
44.8
112.4
123.4
143.6, 171.5
168.2
113.4, 123.4, 152.7, 154.2
74.7, 122.7
25.8, 30.3, 74.7, 77.1
112.9, 135.6, 160.4
74.7, 113.4, 122.7, 152.7,
154.2, 155.3
7.36
7.53
129.1 129.1, 130.6, 155.3
129.6, 130.6 129.1, 129.6, 135.6
11.66
–
143.6, 171.5
10
1.39
1.48
24.6
29.4
29.4, 45.6, 68.0
24.6, 45.6, 76.8, 68.0,
153.2
1.89
2.10
2.26
2.54
3.01
3.34
6.19
7.32
23.0
9.4
168.2
115.6, 123.7, 148.2, 153.2
145.8, 173.0
76.8, 121.7
20.2
45.6
26.2
45.6
112.7
123.7
HMBC correlations also allow to draw conclu-
sions regarding orientation of hydrogen atoms in
conformationally unrestricted pyran ring of the com-
pound. Two doublets of two nonequivalent protons
with chemical shifts at ꢀ ¼ 3.25 and 2.51 ppm are
145.8, 173.0
24.6, 29.4, 68.0, 76.8
111.5, 136.3, 160.8
76.8, 115.6, 121.7, 148.2,
153.2, 155.4
1
7.47
7.56
126.4 126.4, 130.1, 155.4
128.7, 130.1 126.4, 128.7. 136.3
observed in the H NMR spectra. The latter of the
signals is correlated with the 13C-signal of the C-5a
atom, while the signal at ꢀ ¼ 3.25 ppm is not; a lack
of HMBC correlation means that a corresponding
spin–spin coupling constant 3J(H,C) is close to zero,
which is possible only when dihedral angle between
H – C-7 and C-6–C-5a bonds is close to 90ꢁ. This
implies that the H-7 proton with a chemical shift of
3.25 ppm assumes axial (pro-R) orientation, while
the signal at 2.51 ppm corresponds to an equatorial
(pro-S) hydrogen atom. Similarly, it can be shown
11
1.42
1.48
26.3
31.0
31.0, 44.6, 75.4
26.3, 44.6, 75.4, 76.9,
153.2
1.86
2.11
2.24
2.85
3.15
6.18
6.79
7.17
7.28
23.0
9.2
20.1
44.6
44.6
112.7
168.2
118.9, 123.7, 148.2, 153.2
148.3, 174.1
76.9, 121.7
26.3, 31.0, 75.4, 76.9
111.5, 140.0, 160.8
124.4, 129.0 121.6, 129.0, 135.3
121.6
123.7
121.6, 124.4, 148.3, 174.1
1
76.9, 118.9, 121.7, 148.2,
153.2, 155.4
126.4, 128.0, 155.4
that a methyl group 8-CH3, which gives a H NMR
signal at ꢀ ¼ 1.47 ppm, is oriented equatorially (pro-
S), based on the presence of correlation of the signal
of its protons with the 13C NMR signal of the nodal
7.42
7.59
126.4
128.0, 128.7 126.4, 128.7, 140.0

Functionalized 8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]chromene-2,6-diones
1395
Agilent 1100 LC=MSD instrument with chemical ionization
(CI).
6-Acetyl-7-hydroxy-8-methyl-4-phenyl-2H-chromene-2-
one, which was used to obtain 8,8,10-trimethyl-4-phenyl-7,8-
dihydropyrano[3,2-g]chromene-2,6-dione (1), was synthesized
from a corresponding 7-hydroxy-8-methyl-4-phenylcoumarin
by acylation followed by a Fries rearrangement [16].
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione (1, C21H18O4)
To a solution of 5.89 g 6-acetyl-7-hydroxy-8-methyl-4-phenyl-
2H-chromene-2-one (20 mmol) in 40cm3 acetonitrile, 5.1 cm3
pyrrolidine (50 mmol) and 10.3cm3 acetone (14 mmol) were
added. The reaction mixture was kept at 45ꢁC for 8 h
(the reaction completeness was monitored with TLC). The re-
sulting solution was diluted with ice H2O, acidified to pH 5
and filtered. Recrystallization from acetonitrile afforded 3.76 g
(56%) 1. Mp 185–186ꢁC; 1H NMR: ꢀ ¼ 1.47 (s, CH3-8), 2.30
(CH3-10), 2.77 (s, CH2-7), 6.21 (s, H-3), 7.46 (m, H-20, H-60),
7.56 (m, H-30, H-40, H-50), 7.70 (s, H-5) ppm; MS: m=z ¼
335.4 ([MH]þ).
Fig. 2 Heteronuclear correlations in compound 9
4
C-9a atom via four bonds. The fact that J(H,C) be-
tween these atoms is visible can be explained by the
zig-zag conformation of chemical bonds between
them (W-conformation). The structure of 10 and 11
was confirmed similarly.
Therefore, it was shown that among the two
possibilities (C-2 and C-6), the nitrogen-containing
nucleophilic reagents used selectively attack the
8,8,10-trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano-
[3,2-g]chromene-2,6-dione at position 6. In this
way, a series of nitrogen-containing functionalized
derivatives of neoflavones was obtained; these com-
pounds are of great interest regarding their physico-
chemical properties and biological activity.
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-hydrazone (2, C21H20N2O3)
To a solution of 0.33 g 1 (1 mmol) in 5 cm3 anhydr. pyridine
1.5–3 mmol of hydrazine hydrate were added. The reaction
mixture was boiled for 1 h (the reaction completeness was
monitored with TLC). After the reaction was complete, the
mixture was poured in 50 cm3 of ice-H2O, acidified to neu-
tral pH and filtered. Recrystallization from propan-2-ol
afforded 0.28 g (82%) 2. Mp 228–229ꢁC; MS: m=z ¼ 349.4
([MH]þ).
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-oxime (3, C21H19NO4)
To a solution of 0.33 g 1 (1mmol) in 5 cm3 anhydr. pyridine
1.5–3 mmol of hydroxylamine hydrochloride were added. The
reaction mixture was kept on an oil bath at 120–150ꢁC for 1 h
(the reaction completeness was monitored with TLC). After
the reaction was complete, the mixture was poured in 50cm3
of 5% acetic acid and filtered. Recrystallization from propan-
2-ol afforded 0.3g (88%) 3. Mp 284–285ꢁC; MS: m=z ¼
350.4 ([MH]þ).
Experimental
Reaction flow and identity of obtained compounds was con-
trolled with TLC on Merck F254 plates using chloroform:
methanol (9=1, v=v) and (95=5, v=v) systems as eluents.
Melting points were determined using a Kofler-type Leica
Galen III micro hot stage microscope. NMR spectra were
recorded on a Mercury-400 spectrometer (spectrometer fre-
General procedure for the preparation of 8,8,10-trimethyl-4-
phenyl-7,8-dihydropyrano[3,2-g]chromene-2,6-dione thio-
semicarbazones (4–6)
To a solution of 1.1g 1 (3mmol) in 10cm3 ethanol an alco-
holic solution of 3.5 mmol of a corresponding thiosemicar-
bazide with 1 cm3 HCl was added dropwise. The reaction
mixture was kept on a water bath for 3–5 h. The formed
precipitate was filtered off and crystallized from propan-2-ol.
1
quency for H: 400 MHz, 13C: 100 MHz) from DMSO-d6 so-
lutions. The TMS signal was used as an internal standard.
HMQC spectra were acquired as 128ꢀ32 data matrices with
1
spectral ranges: for H–4 kHz, for 13C–21kHz; mixing time
1
corresponds to ICH ¼ 140 Hz. HMBC spectra were acquired
as 400ꢀ32 data matrices with spectral ranges: for 1H–4 kHz,
2–3
for 13C–21kHz; mixing time corresponds to
I
CH
¼ 8 Hz.
Spectra were measured with detection on protons and gradient
selection of signals. Elemental analyses for C, H, and N were
conducted using a Perkin-Elmer C, H, and N Analyzer, their
results were found to be in good agreement (ꢂ0.2%) with
the calculated values. Mass spectra were recorded on an
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-thiosemicarbazone (4, C22H21N3O3S)
Yield 1.14 g (85%); mp 257–259ꢁC; MS: m=z ¼ 408.5
([MH]þ).

1396
V. S. Moskvina et al.
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-(N-methylthiosemicarbazone)
(5, C23H23N3O3S)
N-[30-Acetyl-2,2,10-trimethyl-8-oxo-6-phenyl-2,3-dihydro-
30H,8H-spiro[pyrano[3,2-g]chromene-4,20-[1,3,4]-
thiadiazol]-50-yl]-N-methylacetamide (10, C27H27N3O5S)
Yield 0.26 g (52%); mp 256–258ꢁC; MS: m=z ¼ 506.6
([MH]þ).
Yield 0.98 g (61%); mp 268–270ꢁC; MS: m=z ¼ 422.5
([MH]þ).
8,8,10-Trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-(N-phenylthiosemicarbazone)
(6, C28H25N3O3S)
N-[30-Acetyl-2,2,10-trimethyl-8-oxo-6-phenyl-2,3-dihydro-
30H,8H-spiro[pyrano[3,2-g]chromene-4,20-[1,3,4]-
thiadiazol]-50-yl]-N-phenylacetamide (11, C32H29N3O5S)
Yield 0.23 g (41%); mp 239–240ꢁC; MS: m=z ¼ 568.7
([MH]þ).
Yield 0.98 g (61%); mp 254–256ꢁC; MS: m=z ¼ 484.6
([MH]þ).
General procedure for the preparation of acyl derivatives
of 8,8,10-trimethyl-4-phenyl-7,8-dihydropyrano[3,2-g]-
chromene-2,6-dione 6-hydrazone 7 and 6-oxime 8
A suspension of 1 mmol of hydrazone 2 or oxime 3 in 0.2 cm3
acetic anhydride (2mmol) was heated in the presence of
catalytic quantities of pyridine (2–3 drops) until complete
dissolution. The reaction solution was then kept at room tem-
perature until a precipitate was formed, then the reaction mix-
ture was introduced into 50cm3 of ice H2O. The precipitate
was filtered off and crystallized from methanol.
Acknowledgements
V.M. thanks the DAAD, Euler program, for a fellowship. The
authors acknowledge Thomas K. Huhn (Fachbereich Chemie
¨
der Universitat Konstanz) for technical support.
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8,8,10-Trimethyl-4-phenyl-7,8-dihydro-2H,6H-pyrano[3,2-g]-
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A solution of 1 mmol of a corresponding thiosemicarbazone
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temperature and then poured on ice. The formed precipitate
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N-[30-Acetyl-2,2,10-trimethyl-8-oxo-6-phenyl-2,3-dihydro-
30H,8H-spiro[pyrano[3,2-g]chromene-4,20-[1,3,4]-
thiadiazol]-50-yl]acetamide (9, C26H25N3O5S)
Yield 0.29 g (60%); mp 241–243ꢁC; MS: m=z ¼ 492.6
([MH]þ).