Phosphorylation of 3-hydroxy- and 5,7-dihydroxyflavones with hexaethylphosphorous triamide

Article abstract of DOI:10.1007/s11172-005-0195-6

The reactions of 3-hydroxy- and 5,7-dihydroxyflavones with hexaethylphosphorous triamide proceed according to a classical scheme, but the reaction of 5,7-dihydroxyflavone occurs regioselectively. Dismutation of phosphites, which has been studied earlier o

Full text of DOI:10.1007/s11172-005-0195-6

2810
Russian Chemical Bulletin, International Edition, Vol. 53, No. 12, pp. 2810—2815, December, 2004
Phosphorylation of 3ꢀhydroxyꢀ and 5,7ꢀdihydroxyflavones
with hexaethylphosphorous triamide
a
b
b
a
T. V. Dudakova,a M. P. Koroteev, K. A. Lyssenko, M. Yu. Antipin, and E. E. Nifant´ev
ꢀ
aDepartment of Chemistry, Moscow Pedagogical State University,
3 Nesvizhskii per., 119021 Moscow, Russian Federation.
Fax: +7 (095) 246 7766. Eꢀmail: chemdept@mtuꢀnet.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085. Eꢀmail: kostya@xray.ineos.ac.ru
The reactions of 3ꢀhydroxyꢀ and 5,7ꢀdihydroxyflavones with hexaethylphosphorous triamide
proceed according to a classical scheme, but the reaction of 5,7ꢀdihydroxyflavone occurs
regioselectively. Dismutation of phosphites, which has been studied earlier only for the simꢀ
plest aryl systems, is extended to flavonoids.
Key words: flavonoids, 3ꢀhydroxyflavone, 5,7ꢀdihydroxyflavone, phosphorylation, disꢀ
mutation.
Recently,1,2 our laboratory has begun to study phosꢀ
hydroxyflavones (2). The reactions of compounds 1 and 2
with an equimolar amount of hexaethylphosphorous
triamide (HEPTA) at room temperature afforded the corꢀ
responding diamidophosphites 3 and 4. The reaction was
monitored by TLC and 31P NMR spectroscopy (δP 142.8
and 131.5 for compounds 3 and 4, respectively). The
yields of the reaction products, which were calculated
from the integral intensities of the corresponding signals
in the 31P NMR spectra, were ~95%. Diamidophosphites
3 and 4 were used without additional purification in the
reaction with elemental sulfur at 60 °C to prepare thionoꢀ
phorylation of known flavonoids, viz., quercetine and
dihydroquercetine, with trivalent phosphorus compounds.
This field of investigation is of interest, on the one hand,
from the viewpoint of the characteristic features of the
chemistry of these compounds, which are determined by
their multifunctionality, and, on the other hand, in the
design of new biologically active compounds based on
accessible natural products.
In continuation of our studies, we examined phosphoꢀ
rylation of new flavonoids, viz., 3ꢀhydroxyꢀ (1) and 5,7ꢀdiꢀ
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2698—2702, December, 2004.
1066ꢀ5285/04/5312ꢀ2810 © 2004 Springer Science+Business Media, Inc.

Phosphorylation of flavones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2811
H(3O)
O(3)
C(5)
O(2)
C(4)
C(10)
C(9)
C(6)
C(7)
C(3)
C(2)
C(12)
C(11)
C(6´)
O(4)
P(1)
C(1´)
C(8)
O(1)
C(5´)
C(4´)
N(1)
S(1)
C(18)
C(17)
C(2´)
C(14)
N(2)
C(13)
C(3´)
C(15)
C(16)
Fig. 1. Structure of thionophosphate 6.
Table 1. Bond lengths (d) and bond angles (ω) in comꢀ
pound 6 determined by Xꢀray diffraction analysis and in the
TEDAMTP molecule based on the results of B3PW91/6ꢀ311G*
calculations
phosphates 5 (δP 80.6) and 6 (δP 75.8), which were isoꢀ
lated in the individual state by column chromatography
(Scheme 1).
Study by 1H NMR spectroscopy demonstrated that
compound 6 is a monosubstitution product of the flaꢀ
vonoid moiety at position 7. This reaction proceeds
regioselectively due to the presence of the strong intramoꢀ
lecular C(4)=O...H—O—C(5) hydrogen bond, which subꢀ
stantially decreases the reactivity of the C(5)OH group in
this transformation. Compound 6 is characterized by magꢀ
netic nonequivalence of the methylene protons of the
diethylamide fragments (1H NMR spectroscopic data).
Parameter
6
TEDAMTP
d/Å
Bond
P(1)—S(1)
P(1)—N(1)
P(1)—N(2)
P(1)—O(4)
O(1)—C(2)
O(1)—C(9)
O(2)—C(4)
O(3)—C(5)
C(2)—C(3)
C(3)—C(4)
C(5)—C(6)
C(5)—C(10)
C(4)—C(10)
C(9)—C(10)
1.9323(5)
1.650(1)
1.631(1)
1.627(1)
1.360(2)
1.368(1)
1.251(2)
1.346(2)
1.352(2)
1.436(2)
1.382(2)
1.412(2)
1.449(2)
1.393(2)
1.967
1.706
1.686
1.656
—
—
—
—
—
—
—
—
—
2
The geminal protonꢀproton coupling constant JH,H is
26.0 Hz, and the vicinal protonꢀphosphorus coupling conꢀ
3
stants JH,P are 13.7 and 14.3 Hz. In the NMR spectrum
of compound 5, the methylene protons are magnetically
3
equivalent, and the coupling constant JH,P is somewhat
smaller (12.5 Hz).
The structure of compound 6 was additionally studied
by Xꢀray diffraction. The overall view of the molecule is
shown in Fig. 1. The selected geometric parameters are
given in Table 1.
—
Angle
ω/deg
O(4)—P(1)—N(2)
O(4)—P(1)—N(1)
N(2)—P(1)—N(1)
O(4)—P(1)—S(1)
N(2)—P(1)—S(1)
N(1)—P(1)—S(1)
C(13)—N(1)—C(11)
C(13)—N(1)—P(1)
C(11)—N(1)—P(1)
C(15)—N(2)—C(17)
C(15)—N(2)—P(1)
C(17)—N(2)—P(1)
C(2)—O(1)—C(9)
106.72(6)
95.30(6)
105.93(6)
113.07(4)
114.39(5)
119.27(5)
115.4(1)
116.5(1)
118.06(9)
116.1(1)
124.3(1)
119.48(9)
120.0(1)
106.9
95.8
Analysis of the bond lengths and bond angles in the
flavonoid fragment demonstrated that they are virtuꢀ
ally identical to the corresponding parameters of the
5ꢀhydroxyꢀ7ꢀmethoxyflavone (HMF) molecule.3 The
O(2)...O(3) distance, which characterizes the strength of
the intramolecular O—H...O hydrogen bond, is 2.589(2)
and 2.582 Å in compound 6 and HMF, respectively. Slight
differences in the geometry, in particular, in the twist
angle of the ring B (C(2´)—C(1´)—C(2)—O(1) torsion
angles are 3.8 and 23°, respectively), are determined by
the crystal packing effects. Analysis of intermolecular conꢀ
104.9
114.5
113.5
119.2
114.4
116.0
115.1
117.2
122.6
119.9
—

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Dudakova et al.
O(3)
C(5)
O(2)
C(4)
C(3´A)
C(4´A)
C(3)
C(6)
C(2´A)
C(1´A)
C(10)
C(9)
C(5´A)
C(8A)
O(1A) C(2)
C(7)
C(6´)
C(5´)
C(6´A)
C(7A)
O(1)
C(2A)
C(9A)
C(8)
C(1´)
C(10A)
C(2´)
C(6A)
C(3A)
C(5A)
O(3A)
C(4´)
C(4A)
O(2A)
C(3´)
Fig. 2. Stackedꢀbonded dimer 6.
tacts demonstrated that, although stacking interactions
occur in both compounds, the distance between the rings
and their mutual arrangement are somewhat different. In
HMF, there is an interaction between the rings A and C
with the shortest intermolecular C(4)...C(9) contact
(3.33 Å), whereas stacking interactions between all
rings occur in compound 6 (Fig. 2) with the shortest
C(4´)...C(5A) and C(2´)...C(4A) distances (3.34 and
3.40 Å). Apparently, these differences in the character of
stacking interactions are responsible for a substantial shortꢀ
ening of the O(1)—C(9) bond in molecule 6 (1.368(1) Å)
compared to that in HMF (1.381 Å).
The diethylamido groups in the thionophosphate fragꢀ
ment are noticeably different. The sums of the angles at
the N(1) and N(2) atoms are 350.1(1) and 359.9(1)°, reꢀ
spectively. In addition, the differences in the configuraꢀ
tion lead also to variations in the P—N bond lengths.
Shortening of the P(1)—N(2) bond in the planar NEt2
group by 0.02 Å suggests the presence of the conjugation
between the P=S bond and the lone electron pair of
the N(1) atom. Actually, the P=S bond lies in the
C(17)—N(2)—C(18) plane (the C(15)—N(2)—P(1)—S(1)
torsion angle is 3.9°). The lone electron pair of the N(1)
atom is antiperiplanar with respect to the P(1)—S(1) bond
(the C(13)—N(1)—P(1)—S(1) torsion angle is 74.3°),
which is favorable for an anomeric interaction, viz., the
charge transfer from the lone electron pair of the N(1)
atom to the antibonding σ orbital of the P—S bond.
However, this nonequivalence of the NEt2 groups in
the thionophosphate fragment is not unique for comꢀ
pound 6. Analysis of the data retrieved from the Camꢀ
bridge Structural Database (CSD)4 demonstrated that one
NAlk2 group is planar in almost all structures containing
the OP(=S)(NAlk2)2 fragment, whereas another NAlk2
group has a pyramidal configuration. The P=S bond in
these compounds, like that in molecule 6, is coplanar
with the flattened NAlk2 group. It should be noted that if
the P atom is bound to only one NAlk2 group, the latter is
virtually always flattened. As an example we refer to the
crystal structure of 1,6ꢀbisꢀOꢀ(N,Nꢀtetraethyldiamidoꢀ
thionophosphoryl)galactitol 2,3:4,5ꢀbisꢀ(Nꢀdiethylamidoꢀ
cyclothionophosphate), whose molecule contains two
OP(=S)(NEt2)2 groups and the O2P(=S)NEt2 group.5 In
this compound, the amino group in the O2P(=S)(NEt2)2
fragment has a planar configuration (the sum of the angles
at the nitrogen atom is 359.8°). By contrast, only one
NEt2 group in OP(=S)(NEt2)2 is planar (the sums of the
angles at the nitrogen atoms are in a range of 359.6—360°),
whereas the second NEt2 group is pyramidal (the sums
of the angles at the nitrogen atoms are in a range
of 348.1—354.7°).
To estimate whether the difference in the P—N bond
lengths is a consequence of conjugation with the P=S
bond and to examine the possibility of existence of the
aboveꢀmentioned anomeric interaction, we carried out
quantumꢀchemical calculations for the model comꢀ
pound methyl N,Nꢀtetraethyldiamidothionophosphate
MeOP(S)(NEt2)2 (TEDAMTP). The calculations were
performed with full geometry optimization by the
B3PW91/6ꢀ311G* method using the GAUSSIANꢀ98 proꢀ
gram package.6 In spite of the fact that calculations at this
level of theory give slightly overestimated bond lengths
with the P atom, the main characteristic features revealed
for 6 are observed also for the isolated TEDAMTP molꢀ

Phosphorylation of flavones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2813
Scheme 2
ecule (see Table 1). The sums of the angles at the N(1)
and N(2) atoms are 345.5 and 359.8°, respectively. The
difference between the P(1)—N(1) and P(1)—N(2) bond
lengths (1.686 and 1.706 Å, respectively) is equal to that
observed in the crystal ((0.02 Å).
Topological analysis of the electron density function
for the TEDAMTP compound demonstrated that, in spite
of shortening of the P(1)—N(2) bond compared to the
P(1)—N(1) bond, the electron densities (1.208 and
1.216 e Å–3) at the corresponding critical points (3, –1)
are virtually identical. Moreover, the P(1)—N(1) and
P(1)—N(2) bonds are characterized by similar ellipticities
(ε) (0.187 and 0.197 Å, respectively; for comparison, ε for
the P(1)—O(4) bond is 0.075 Å), which serve as a meaꢀ
sure of the deviation of the electron density distribution
from cylindrical symmetry and, consequently, show the
contribution of the π component.
The NBO analysis demonstrated that the high ellipticꢀ
ity of the P(1)—N(1) bond results from an interaction
between the lone electron pair of the N atom and the
antibonding orbital of the P—S bond with an energy of
8.97 kcal mol–1. The low energy of this anomeric interacꢀ
tion and the similar populations of the orbitals correꢀ
sponding to the lone electron pairs of the N(1) and N(2)
atoms (1.85 and 1.82) suggest that the conjugation of the
N(2)Et2 group with the P=S bond is rather weak.
and gives the target products in high yields. Phosphite
based on 5,7ꢀdihydroxyflavone contains the pseudochiral
P atom. This complex spatial organization is retained in
solution, as evidenced by the magnetic nonequivalence of
the methylene protons of the diethylamido groups obꢀ
served in 1H NMR spectra. Dismutation of phosphites of
3ꢀhydroxyꢀ and 5,7ꢀdihydroxyflavones was investigated.
Storage of crude phosphites 3 and 4 for two days afꢀ
forded phosphites of another type, but the conversion
(which was determined from the integral intensity ratio in
the 31P NMR spectrum) was no higher than 20%. Heating
of phosphites 3 and 4 at 60 °C for 8 h led (31P NMR
spectroscopic data) to the transformation of diamidoꢀ
phosphite 3 (δP 131.5) into monoamidophosphite 7
(δP 139.2) and the transformation of phosphite 4 (δP 142.8)
into monoamidophosphite 8 (δP 147.1). The yields of the
products increased to 50%. The resulting mixtures of phosꢀ
phites were subjected to sulfurization. Column chromaꢀ
tography afforded thionophosphates 9 (δP 64.7) and 10
(δP 71.9), which contain two flavonoid fragments linked
Experimental
All experiments with trivalent phosphorus compounds were
carried out under dry nitrogen in dry solvents, which were puriꢀ
fied according to standard procedures. The 1H NMR spectra
were recorded on a Bruker WPꢀ250 instrument in CDCl3 with
Me4Si as the internal standard. The 31P NMR spectra were
measured on a Bruker WPꢀ80 instrument (32.4 MHz) with
H3PO4 as the external standard. The reactions were monitored
and the purity of the products was checked by TLC on Silufol
UVꢀ254 plates using a 3 : 1 hexane—dioxane mixture as the
eluent. The chromatograms were visualized in an iodine chamꢀ
ber or by heating. Adsorption chromatography was carried out
on silica gel L 40/60 µm (Merck). Commercial reagents were
purchased from Aldrich, and HEPTA was prepared according to
a known procedure.8
Flavonꢀ3ꢀyl N,N,N´,N´ꢀtetraethyldiamidothionophosphate
(5). Hexaethylphosphorous triamide (0.27 g, 1.1 mmol) was
added dropwise to a suspension containing 3ꢀhydroxyflavone 1
(0.26 g, 1.1 mmol) and dry dioxane (5 mL). The reaction was
monitored by TLC and 31P NMR spectroscopy. The reaction
mixture was kept at room temperature for 4 h. The solvent was
distilled off in vacuo. The resulting oily compound, flavonꢀ3ꢀyl
3
through the P atom. The constants JH,P for these comꢀ
pounds are analogous to those for the monomeric prodꢀ
ucts. This reaction pathway can be attributable to disꢀ
mutation (Scheme 2).
Unfortunately, because of high hygroscopicity of diꢀ
oxane used as the solvent, we failed to detect the second
reaction product, viz., HEPTA, in the free state. Neverꢀ
theless, we observed accumulation of its hydrolysis prodꢀ
uct, viz., tetraethylphosphorous diamide, in the reaction
mixture. In addition, dismutation afforded free flavonoids,
which were isolated in trace amounts by column chromaꢀ
tography. Analogous dismutation has been studied in deꢀ
tail earlier7 for other aryl diamidophosphites, which were
prepared starting from certain phenols and naphthols.
To summarize, phosphorylation of flavones with
hexaethylphosphorous triamide occurs regioselectively
N,N,N´,N´ꢀtetraethyldiamidophosphite, (3) (δ 142.8) was disꢀ
P
solved in anhydrous benzene, and then sulfur (0.04 g, 1.25 mmol)
was added. To accelerate sulfurization, 1—2 drops of triethyꢀ
lamine were added and the reaction mixture was heated at 60 °C
for 3 h. The solvent was distilled off in vacuo. Thionophosphate 5

2814
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Dudakova et al.
was isolated by column chromatography in a yield of 0.29 g
(62%), m.p. 109—111 °C, Rf 0.6. Found (%): C, 62.10;
H, 6.61; N, 6.34; P, 7.01; S, 7.18. C23H29N2O3PS. Calcuꢀ
lated (%): C, 62.14; H, 6.58; N, 6.30; P, 6.97; S, 7.21. 31P NMR
Table 2. Selected crystallographic data and details of the strucꢀ
ture refinement of compound 6
Parameter
Characteristic
1
3
(C6H6), δ: 80.6. H NMR, δ: 8.27 (dd, 1 H, H(5), J = 7.9 Hz,
3
3
4J = 1.8 Hz); 7.37 (ddd, 1 H, H(6), J = 8.1 Hz, J = 7.3 Hz,
Molecular formula
Molecular weight
C23H29N2O4PS
460.51
3
3
4J = 1.6 Hz); 7.64 (ddd, 1 H, H(7), J = 8.4 Hz, J = 7.0 Hz,
4J = 1.6 Hz); 7.45 (dd, 1 H, H(8), 3J = 8.1 Hz, 4J = 1.6 Hz); 7.79
Crystal system
Space group
Triclinic
P1
3
4
(dd, 2 H, H(2´), H(6´), J = 7.3 Hz, J = 1.6 Hz); 7.45—7.50
(m, 3 H, H(3´), H(4´), H(5´)); 3.07 (m, 8 H, NCH2Me); 1.04
(t, 12 H, NCH2CH3,3J = 7.1 Hz).
T/K
120
Diffractometer
Z (Z´)
«SMART CCD»
2 (1)
5ꢀHydroxyflavonꢀ7ꢀyl N,N,N´,N´ꢀtetraethyldiamidothionoꢀ
phosphate (6) was prepared by the reaction of 5,7ꢀdihydroxyꢀ
flavone (0.33 g, 1.29 mmol), HEPTA (0.32 g, 0.129 mmol), and
sulfur (0.05 g, 1.56 mmol) analogously to the synthesis of prodꢀ
uct 5. Intermediate 5ꢀhydroxyflavonꢀ7ꢀyl N,N,N´,N´ꢀtetraethylꢀ
a/Å
b/Å
с/Å
α/deg
7.7412(5)
11.5874(8)
13.8553(9)
101.356(1)
105.212(1)
103.009(1)
1124.4(1)
1.360
β/deg
diamidophosphite (4) (δ 142.8) was used without additional
P
γ/deg
purification. The yield was 0.44 g (71%), m.p. 123—125 °C,
Rf 0.5. Found (%): C, 59.81; H, 6.38; N, 6.04; P, 6.71; S, 7.02.
C23H29N2O4PS. Calculated (%) C, 59.87; H, 6.35; N, 6.08;
P, 6.73; S, 6.96. 31P NMR (C6H6), δ: 75.8. 1H NMR, δ: 6.70 (s,
1 H, H(3)); 6.58 (dd, 1 H, H(6), 4J = 2.2 Hz, 4JH(6),P = 1.1 Hz);
V/Å3
dcalc/g cm–3
µ/cm–1
2.48
F(000)
488
4
4
Scan mode
ω
6.99 (dd, 1 H, H(8), J = 2.2 Hz, JH(8),P = 1.2 Hz); 7.89 (dd,
3
4
2θmax/deg
60
2 H, H(2´), H(6´), J = 7.4 Hz, J = 1.5 Hz); 7.53—7.54 (m,
3 H, H(3´), H(4´), H(5´)); 12.69 (s, 1 H, OH); 3.25 (m, 8 H,
NCH2Me); 1.18 (t, 12 H, NCH2CH3, 3J = 7.0 Hz).
Number of measured reflections
13366
Number of independent reflections
6475
Number of reflections with I > 2σ(I )
Rint
Number of parameters in refinement
GOF
R1
wR2
5620
0.0439
288
1.047
0.0439
0.0995
Bis(flavonꢀ3ꢀyl) N,Nꢀdiethylamidothionophosphate (9). Prodꢀ
uct 3 was synthesized according to the aboveꢀdescribed proceꢀ
dure from 3ꢀhydroxyflavone (0.5 g, 2.13 mmol) and HEPTA
(0.52 g, 0.23 mmol). A dioxane solution containing this product
was heated at 60 °C for 8 h. The reaction was monitored by TLC
and 31P NMR spectroscopy. Sulfur (0.08 g, 2.5 mmol) and
1—2 drops of triethylamine (as the catalyst) were added to the
Residual electron
0.526/–0.345
density/e Å–3, ρmin/ρ
resulting mixture of phosphite 3 (δ 142.8) and bis(flavonꢀ3ꢀyl)
max
P
N,Nꢀdiethylamidophosphite (7) (δ 147.1) characterized by the
P
integral intensity ratio of 1 : 1. The reaction mixture was heated
at 60 °C for 3 h. The solvent was distilled off in vacuo, and
thionophosphate 9 was isolated by column chromatography.
The yield was 0.55 g (43%), m.p. 218—220 °C, Rf 0.3. Found
(%): C, 67.03; H, 4.66; N, 2.33; P, 5.10; S, 5.21. C34H28NO6PS.
Calculated (%): C, 66.99; H, 4.63; N, 2.30; P, 5.08; S, 5.26.
31P NMR (C6H6) δ: 70.1. 1H NMR, δ: 8.19 (dd, 2 H, H(5), 3J =
OH); 3.49 (m, 4 H, NCH2Me); 1.22 (t, 6 H, NCH2CH3,
3J = 7.0 Hz).
Single crystals of compound 6 were prepared by crystallizaꢀ
tion from a hexane—dioxane mixture. Xꢀray diffraction study
was carried out at 120 К on an automated SMART CCD
diffractometer. The structure was solved by direct methods and
4
3
3
refined against F2 by the leastꢀsquares method with anisotroꢀ
8.0 Hz, J = 1.5 Hz); 7.37 (ddd, 2 H, H(6), J = 8.1 Hz, J =
hkl
4
3
3
7.3 Hz, J = 1.6 Hz); 7.65 (ddd, 2 H, H(7), J = 8.4 Hz, J =
pic displacement parameters for all nonhydrogen atoms. The
H atoms were located from difference Fourier maps and refined
isotropically. The principal crystallographic characteristics and
details of the structure refinement are given in Table 2. All
calculations were carried out on an IBMꢀPC/AT using the
SHELXTL PLUS program package.9
Quantumꢀchemical calculations were carried out by the
B3PW91/6ꢀ311G* method with full geometry optimization usꢀ
ing the GAUSSIANꢀ98 program package.6 The electronic strucꢀ
ture was studied in the localized orbital approximation using
NBO analysis10 and in terms of the topological theory of Atoms
in Molecules.11
4
3
4
7.0 Hz, J = 1.6 Hz); 7.47 (dd, 2 H, H(8), J = 8.1 Hz, J =
2.2 Hz); 7.83 (dd, 4 H, H(2´), H(6´), 3J = 7.6 Hz, 4J = 1.2 Hz);
7.28—7.37 (m, 6 H, H(3´), H(4´), H(5´)); 3.41 (m, 4 H,
3
NCH2Me); 1.05 (t, 6 H, NCH2CH3, J = 7.1 Hz).
Bis(5ꢀhydroxyflavonꢀ7ꢀyl) N,Nꢀdiethylamidothionophosphate
(10) was prepared by the reaction of 5,7ꢀhydroxyflavone (0.5 g,
1.96 mmol), HEPTA (0.49 g, 1.96 mmol), and sulfur (0.08 g,
2.5 mol) analogously to the synthesis of product 9. The resultꢀ
ing bis(5ꢀhydroxyflavonꢀ7ꢀyl) N,Nꢀdiethylamidophosphite (8)
(δ 139.2) was used without isolation. The yield was 0.49 g
P
(38%), m.p. 210—212 °C, Rf 0.4. Found (%): C, 63.68; H, 4.44;
N, 2.16; P, 4.79; S, 5.05. C34H28NO8PS. Calculated (%):
C, 63.65; H, 4.40; N, 2.18; P, 4.83; S, 5.00. 31P NMR (C6H6),
References
1
δ: 64.7. H NMR, δ: 6.73 (s, 2 H, H(3)); 6.71 (dd, 2 H, H(6),
4J = 2.3 Hz, 4JH(6),P = 1.2 Hz); 6.99 (dd, 2 H, H(8), 4J = 2.2 Hz,
4JH(8),P = 1.2 Hz); 7.90 (dd, 4 H, H(2´), H(6´), 3J = 7.4 Hz, 4J =
1.5 Hz); 7.55 (m, 6 H, H(3´), H(4´), H(5´)); 12.77 (s, 1 H,
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Received July 20, 2004;
in revised form September 30, 2004