Synthesis and reactions of reduced flavones

Article abstract of DOI:10.1039/a602245f

The cycloadditions of a series of 4H-pyran-4-ones 3c-e with electron-rich dienes 11a,b to give reduced flavones 12 is described. The subsequent reactions of these reduced flavones with HCl, trifluoroacetic anhydride, ethyl anthranilate 19a and anthranilon

Full text of DOI:10.1039/a602245f

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Synthesis and reactions of reduced flavones
Paul W. Groundwater,*,a,† David E. Hibbs,a Michael B. Hursthousea and
Miklós Nyergesb
a Department of Chemistry, University of Wales, Cardiff, PO Box 912, Cardiff CF1 3TB, UK
b Research Group of the Hungarian Academy of Sciences,
Department of Organic Chemical Technology, Technical University of Budapest,
H-1521 Budapest POB 91, Hungary
The cycloadditions of a series of 4H -pyran-4-ones 3c–e with electron-rich dienes 11a,b to give reduced
flavones 12 is described. The subsequent reactions of these reduced flavones with H Cl, trifluoroacetic
anhydride, ethyl anthranilate 19a and anthranilonitrile 19b is also described.
We have recently described the synthesis of a series of
Results and discussion
pyranoacridinones, e.g. 1,1 which are potent inhibitors of the
Synthesis of 4H-pyran-4-ones
Initially, we required a standard synthesis of a range of substi-
tuted pyranone dienophiles for the Diels–Alder reaction. After
reviewing the literature the following methodologies were used,
mostly with slight modifications. We have prepared the 2-
phenyl-4H-pyran-4-one 3a by a modification of Reynolds’
method (Scheme 1).11 The main differences in our procedure are
spontaneous proliferation of a human-derived gastric carcin-
oma cell line, MKN 45, but are non-cytotoxic.2 A key inter-
mediate in the synthesis of these pyranoacridinones is 7-oxo-
5,6,7,8-tetrahydroflavone 2 and, as part of our ongoing
investigation into the biological potential of these pyrano-
acridinones, we have become interested in an alternative, more
efficient, synthesis of reduced flavones. We have previously
reported a novel method for the synthesis of reduced flavones
based on the Diels–Alder reactions of 4H-pyran-4-ones with
electron-rich dienes.3 To date very little attention has been paid
to cycloadditions of 4H-pyran-4-ones, in contrast to the well-
documented reactivity of 4H-benzopyran-4-ones4–8 or benzo-
thiopyranones.9 The only example of the cycloaddition of 4H-
pyran-4-ones is a footnote by McCombie et al.10 in their paper
on the preparation of these compounds in which pyranone 3c
readily reacted with diazomethane in a 1,3-dipolar cycloaddi-
tion to give the adduct 4. In this paper we describe our experi-
mental procedures for the preparation of these ring systems,
together with some observations on their chemical reactivity.
Scheme 1 Reagents and conditions: i, Ac2O, BF3ؒEt2O; ii, (CH3)2-
NCH(OCH3)2, DMF; iii, HClO4, EtOH
the use of boron trifluoride–diethyl ether rather than gaseous
boron trifluoride, and the work-up procedure in the final step
(three steps, 21% overall yield). The method used first by
Borsche and Peter 12 proved to be an easy route to ethyl 4-oxo-6-
phenyl-4H-pyran-2-carboxylate 3b, in good yield (Scheme 2).
Scheme 2 Reagents and conditions: i, Br2; ii, AcOK, dry EtOH
The preparation of 6-aryl-4-oxo-4H-pyran-3-carboxylates 3c–e
has been described by McCombie et al. (Scheme 3).10 This pro-
cedure is based on simple starting materials with two effective
steps for the formation of the pyranone ring. We have altered
† Current address: School of Health Sciences, University of Sunder-
land, Sunderland SR1 3SD, UK.
J. Chem. Soc., Perkin Trans. 1, 1997
163

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Scheme 3 Reagents and conditions: i, (CH3)2NCH(OCH3)2, 80 ЊC; ii,
ArCOCl, LiN(SiMe3)2, Ϫ70 ЊC; iii, HCl, H2O, room temp.
the method for the synthesis of the intermediate enaminone
10; instead of using a dimethylformamide (DMF)–dimethyl
sulfate adduct, the enaminone 10 was formed by simple heat-
ing of the corresponding keto ester 9 with dimethylform-
amide dimethyl acetal without the presence of any solvent.13
With this modification we have prepared the pyranones 3c–3e
in 40–60% yield.
Fig. 1 X-Ray crystal structure of cycloadduct 12a
Diels–Alder reactions
The pyranone 3a without any additional electron-withdrawing
groups, and the pyranone 3b, were unreactive towards 2-
trimethylsilyloxybuta-1,3-diene 11a and Danishefsky’s diene
11b under normal or forced (neat, 160 ЊC or Lewis-acid cata-
lyst) conditions, while pyranones 3c–3e reacted smoothly with
11b and the reaction resulted in formation of the cycloadducts
12a–c in good yield (Scheme 4). The addition of 3c to 2-
Scheme 5 Reagents and conditions: i, LiBr, Et3N, MeCN, room temp.
of the ortho protons of the 7-phenyl group (7%) whilst there
was no NOE observed between H-7 and H-5.
Deprotection of Diels–Alder adducts
Scheme 4
Treatment of the cycloadducts 12a,b with 0.01  HCl in THF
gave the corresponding desilylated products 16a,b. The brief
treatment of 12 or 16 with trifluoroacetic anhydride (TFAA)
gave the enones 17a,b (Scheme 6). In both the treatment with
hydrochloric acid and the TFAA, epimerisation of H-8a was
observed to give a 1:1 mixture of diastereoisomers. This is
unimportant in the synthesis of the pyranoacridinones, e.g. 1,
since the groups at the 4a- and 8a-positions will be lost upon
aromatisation.
trimethylsilyloxybuta-1,3-diene 11a under the same conditions
proceeded more slowly, due to the lower reactivity of the diene,
and gave the cycloadduct 12d in poor yield (12d could not be
isolated; the ketone 16c was isolated in 16% overall yield, after
treatment of 12d with 0.01  aqueous HCl–THF, followed by
chromatography).
The 1H NMR spectra of the cycloadducts indicate the pres-
ence of only one diastereoisomer, which is quite remarkable as
the analogous process led to a 1 : 1 mixture of diastereoisomers
in the benzopyranone series.4
Reduction of enone 17a
To achieve the synthesis of 7-oxotetrahydroflavone 2 or an ana-
logue the selective reduction of the 5,6-double bond of 17a was
necessary (the direct synthesis of 16c proceeded in poor yield).
Our attempts to reduce 17a by means of PtO2–H2, tris(triphenyl-
phosphine)chlororhodium() (ethanol, 60 ЊC, 40 psi‡),15 or
Red-Al–CuBr 16 were unsuccessful. In all cases only the starting
material was recovered. The reduction of 17a with Red-Al gave
a complex mixture of products. The use of a large excess of
NaBH4 in CH2Cl2 solution resulted in the reduction of the 7-
oxo group quantitatively and selectively, giving a mixture of
diastereoisomers 18 (Scheme 7).
We have attempted to determine the relative stereochemistry
1
of cycloadduct 12a by H{1H} NOE difference spectroscopy,
but irradiation of the doublet for H᎐5 (δ 4.56) gave only a large
NOE to H-6 and a medium NOE to the OMe. Irradiation of
the OMe (δ 3.23) was inconclusive. The 3D structure of the
cycloadduct 12a was therefore determined by X-ray crystal-
lography and shows that the methoxy group at C-5 and the
ester group at C-4a are trans to one another, with the methoxy
group in a pseudo-axial position (Fig. 1).
Similar observations were made when the ester-stabilised
azomethine ylide 14 (generated from imine 13 in the presence of
LiBr as a catalyst) acted as a 4π component in a 1,3-dipolar
cycloaddition;14 whilst 3a,b were unreactive, in the reaction with
pyranone 3d the cycloadduct 15 was formed in good yield
(Scheme 5). The configuration of cycloadduct 15 depicted was
Reaction of reduced flavones with anthranilic acid derivatives
The condensation of 12a or 12b with the primary aromatic
amines under the standard conditions for azeotropic removal
1
verified by H{1H} NOE difference spectroscopy, the irradi-
ation of H-7 (δ 5.14) caused enhancement of H-7a (5%), and
‡ 1 psi = 6894.76 Pa.
164
J. Chem. Soc., Perkin Trans. 1, 1997

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product 20a crystallised out from the reaction mixture after
cooling in both cases. Compounds 21 (identified by comparison
of spectroscopic data with literature values17) and 22a, 22b and
22c were separated by column chromatography as minor prod-
ucts. The same reactivity was observed in the reaction of
anthranilonitrile 19b with 12a. These results suggest that the
reaction with the amine is not regioselective, i.e. unlike our
earlier work with 21 there is no distinction between the two
carbonyl groups.
Experimental
Mps were determined on a Kofler hot-stage and are uncor-
1
rected. H and 13C NMR spectra were acquired on a Bruker
WM360 spectrometer at 360 and 90 MHz respectively. 1H
NMR coupling constants (J ) are given in Hz and chemical
shifts (δ) are relative to an internal standard of tetramethyl-
silane. Low resolution electron impact mass spectra were
obtained on a Varian CH5-D spectrometer. Elemental analyses
were performed on a Perkin-Elmer 240B. IR spectra were
recorded on a Perkin-Elmer 1600 series FT-IR spectrometer
using sodium chloride plates. Thin layer chromatography was
performed on Merck silica gel 60F254 and dry column flash
chromatography on Merck silica gel 60H. Tetrahydrofuran was
dried from sodium–benzophenone.
Scheme 6 Reagents and conditions: i, 0.01  HCl–THF; ii, TFAA,
CH2Cl2
Crystal data for cycloadduct 12a
C24H32O6Si, M = 444.59. Monoclinic, a = 18.303(2), b =
6.7340(5), c = 19.987(3) Å, β = 96.307(12)Њ (by least-squares
refinement of the setting angles for 250 reflections within
θ = 2.05–25.09Њ), V = 2448.2(5) Å3, space group P21/c (14),
Z = 4, Dm = 1.206 g cmϪ3, F(000) = 952. White crystals. Crystal
dimensions 0.25 × 0.18 × 0.14 mm, µ(Mo-Kα) = 0.131 mmϪ1
.
Scheme 7
Data collection and processing
of water, in the presence of a catalytic amount of toluene-p-
sulfonic acid (PTSA), resulted in an interesting degradation of
the flavone ring system (12 was deprotected immediately under
the harsh conditions used) (Scheme 8). From the complex mix-
FAST TV Area detector diffractometer following previously
described procedures.18 From the ranges scanned, 9823 data
were collected (2.05 ≤ θ ≤ 25.09Њ), 3687 unique (Rint = 0.0699).
Structural analysis and refinement
The structure was solved via direct methods (SHELX-S)19 and
2
refined on Fo by full-matrix least-squares (SHELXL-93)20
using all unique data corrected for Lorentz and polarisation
2
factors to final wR (on Fo ) and R (on F) values of 0.1015 and
0.0692 for 287 parameters (non-hydrogen atoms anisotropic;
hydrogens in idealised positions with Uisos tied to the Ueqs of the
parents). The corresponding R values for data with I > 2σ(I) are
0.0973 and 0.0433, respectively. The weighting scheme used was
2
w = 1/[σ2(Fo ) + (0.0467P)2], where P = [max(Fo)2 + 2(Fc)2]/3;
this gave satisfactory agreement analyses. Sources of scattering
factors as in ref. 20. Atomic coordinates, bond lengths and
angles and thermal parameters have been deposited at the
Cambridge Crystallographic Data Centre.§
2-Phenyl-4H-pyran-4-one 3a
(i)
2,2-Difluoro-6-methyl-4-phenyl-1,3,2-dioxaborinin-1-
ylium-2-uide 5. Acetophenone (2.5 g, 20.8 mmol) was dissolved
in acetic anhydride (4.3 g, 47.7 mmol), cooled to 5–10 ЊC and
boron trifluoride–diethyl ether (1.6 g, 11 mmol) was added.
After 2 h stirring at room temperature the reaction mixture was
evaporated in vacuo then diluted with diethyl ether (30 cm3).
The precipitated solid was collected as yellow crystals of the
benzoylacetone–boron trifluoride complex 5 (2.84 g, 65%), mp
146 ЊC (lit.,11 147–150 ЊC) (Found: C, 57.3; H, 4.3. C10H9BF2O2
requires C, 57.2; H, 4.3%); νmax(Nujol)/cmϪ1 1632, 1541 and
Scheme 8 Reagents and conditions: i, toluene, PTSA, reflux
ture of products obtained from the reaction of 12a or 12b with
ethyl anthranilate 19a, three were identified and at least two
by-products remained unidentified (shown by TLC). The main
§ For details, see Instructions for Authors, J. Chem. Soc., Perkin Trans.
1, 1996, Issue 1. Any request to the CCDC for this material should
quote the full literature citation and the reference number 207/62.
J. Chem. Soc., Perkin Trans. 1, 1997
165

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779; δH [(CD3)2SO] 2.50 (3 H, s, CH3), 7.28 (1 H, s, CH) and
7.60–7.90 (5 H, m, Ph); m/z 210 (M+, 24%), 209 (M+ Ϫ 1, 37),
195 (15), 191 (12), 115 (9), 105 (100), 89 (8), 77 (86), 63 (10), 51
(44) and 43 (87).
N,N-dimethylformamide dimethyl acetal at 80 ЊC in the absence
of solvent resulted in the formation of the desired product. The
methanol generated in the reaction was removed in vacuo to
give an oil 10, in quantitative yield, which was used in the next
step without further purification.
(ii)
6-(2-Dimethylaminovinyl)-2,2-difluoro-4-phenyl-1,3,2-
dioxaborinin-1-ylium-2-uide 6. 2,2-Difluoro-6-methyl-4-phenyl-
1,3,2-dioxaborinin-1-ylium-2-uide 5 (1.0 g, 4 mmol) was heated
as a suspension in a mixture of dry N,N-dimethylformamide (2
cm3) and N,N-dimethylformamide dimethyl acetal (0.7 cm3, 5.3
mmol), with stirring, for 1 h at 95–100 ЊC. On cooling, a yellow–
green solid 6 precipitated (0.57 g, 54%), mp 215 ЊC (lit.,11 215–
216 ЊC) (Found: C, 59.0; H, 5.2; N, 5.3. C13H14BF2NO2 requires
C, 58.9; H, 5.3; N, 5.3%); νmax(Nujol)/cmϪ1 1706, 1640, 1565,
1262 and 823; δH (CDCl3) 3.02 (3 H, s, NCH3), 3.25 (3 H, s.
tert-Butyl 2-(dimethylamino)methylene-3-oxobutanoate 10a.
Orange oil; νmax(Nujol)/cmϪ1 2974, 2927, 1690 (C᎐O), 1643
᎐
(C᎐O), 1574, 1486, 1426, 1366, 1291, 1225, 1162, 1114, 1067,
᎐
967, 882 and 850; δH (60 MHz, CDCl3) 1.5 (9 H, s, But), 2.3
(3 H, s, CH CO), 3.0 [6 H, s, N(CH ) ] and 7.5 (1 H, s, CH᎐);
᎐
3
3 2
m/z 213 (M+, 14%), 157 (10), 142 (45), 124 (78), 98 (100), 82
(18), 70 (20), 57 (58) and 43 (95).
Benzyl 2-(dimethylamino)methylene-3-oxobutanoate 10b. Red
oil; νmax(Nujol)/cmϪ1 2927, 1688 (C᎐O), 1641 (C᎐O), 1578, 1422,
᎐
᎐
NCH ), 5.05 [1 H, d, J 12.0, CH᎐CHN(CH ) ], 6.13 (1 H, s,
1362, 1283, 1215, 1187, 1114, 1050, 969, 816, 752 and 700;
δH (60 MHz, CDCl3) 2.2 (3 H, s, CH3), 2.9 [6 H, s, N(CH3)2], 5.1
(2 H, s, CH ), 7.3 (5 H, s, Ph) and 7.6 (1 H, s, CH᎐).
᎐
3
3 2
H-5), 7.41–7.52 (3 H, m, Ph), 7.93 (2 H, d, J 7.9, Ph) and 8.09
[1 H, d, J 12.0, CHN(CH3)2]; m/z 265 (M+, 38%), 246 (30), 221
(41), 200 (25), 158 (27), 146 (17), 132 (28), 118 (50), 97 (62), 77
(69), 69 (93), 55 (60) and 42 (100).
᎐
2
Preparation of 6-aryl-4-oxo-4H-pyran-3-carboxylates 3c, 3d and
3e
(iii) 2-Phenyl-4H-pyran-4-one 3a. Boron complex 6 (0.3 g, 1.13
mmol) was refluxed in ethanol (10 cm3) and 60% aqueous per-
chloric acid (0.5 cm3) for 6 h. The solvent was evaporated and
the residue was dissolved in water (5 cm3) and extracted with
chloroform (3 × 10 cm3). The combined organic layers were
dried over magnesium sulfate and evaporated. The resulting
solid was recrystallised from ethanol to give 2-phenyl-4H-
pyran-4-one 3a as a white solid (0.14 g, 75%), mp 100–102 ЊC
(lit.,11 101–103 ЊC) (Found: C; 76.6; H, 4.8. C10H8O2 requires C,
These were prepared according to the procedure described by
McCombie et al.10
tert-Butyl 4-oxo-6-phenyl-4H-pyran-3-carboxylate 3c. Pale
brown solid (61%), mp 98–100 ЊC (lit.,10 99–102 ЊC) (Found: C,
70.4; H, 6.1. C16H16O4 requires C, 70.6; H, 5.9%); νmax(Nujol)/
cmϪ1 1705 (C᎐O), 1664 (C᎐O), 1347, 1149, 1103, 975, 908, 839
᎐
᎐
and 772; δH (CDCl3) 1.57 (9 H, s, But), 6.84 (1 H, s, H-2), 7.49
(2 H, m, H-3Ј and -5Ј), 7.48 (1 H, m, H-4Ј), 7.75 (2 H, m, H-2Ј
and -6Ј) and 8.78 (1 H, s, H-5); m/z 272 (M+, 20%), 257 (8), 217
(37), 199 (38), 171 (35), 147 (28), 144 (32), 115 (43), 95 (42), 75
(56), 69 (41), 65 (42), 51 (60) and 42 (100).
76.7; H, 4.7%); νmax(Nujol)/cmϪ1 1650 (C᎐O), 1608, 1414, 1255,
᎐
1051, 1015, 925, 891 and 817; δH (CDCl3) 6.40 (1 H, dd, J 5.8 and
2.4, H-5), 6.80 (1 H, d, J 2.4, H-3), 7.46–7.52 (3 H, m, H-3Ј, -4Ј
and -5Ј), 7.75–7.78 (2 H, m, H-2Ј and -6Ј) and 7.87 (1 H, d, J 5.8,
H-6); m/z 172 (M+, 54%), 144 (78), 115 (57), 102 (100), 89 (20),
77 (47), 69 (30) and 51 (52).
tert-Butyl 4-oxo-6-(p-methoxyphenyl)-4H-pyran-3-carboxyl-
ate 3d. Light brown solid (52%), mp 119–120 ЊC (Found: C, 67.5;
H, 6.0. C17H18O5 requires C, 67.5; H, 6.0%); νmax(Nujol)/cmϪ1
1734 (C᎐O), 1644 (C᎐O), 1621, 1604, 1574, 1512, 1399, 1310,
᎐
᎐
Ethyl 4-oxo-6-phenyl-4H-pyran-2-carboxylate 3b
1296, 1251, 1235, 1178, 1160, 1077, 1034, 914, 856 and 785;
δH (CDCl3) 1.54 (9 H, s, But), 3.86 (3 H, s, OMe), 6.75 (1 H, s,
H-2), 6.98–7.02 (2 H, m, H-3Ј and -5Ј), 7.67–7.72 (2 H, m, H-2Ј
and -6Ј) and 8.48 (1 H, s, H-5); m/z 302 (M+ 60%), 287 (5), 247
(51), 229 (60), 202 (78), 174 (40), 161 (54), 146 (47), 135 (60),
115 (41), 102 (45), 89 (55), 77 (56), 69 (53), 63 (54), 57 (100), 53
(64), 43 (57) and 41 (89).
Benzyl 4-oxo-6-phenyl-4H-pyran-3-carboxylate 3e. Bright red
solid (32%), mp 85–89 ЊC (Found: C, 74.5; H, 4.8. C19H14O4
requires C, 74.5; H, 4.6%); νmax(Nujol)/cmϪ1 1706, 1655, 1622,
1395, 1342, 1294, 1266, 1154, 1108, 1025, 994, 969 and 912;
δH (CDCl3) 5.35 (2 H, s, CH2), 6.85 (1 H, s, H-3), 7.29–7.39 (3 H,
m, Ar-H), 7.43–7.52 (5 H, m, Ar-H), 7.71–7.74 (2 H, m, H-2Ј and
-6Ј) and 8.58 (1 H, s, H-5); m/z 306 (M+, 5%), 288 (3), 200 (88),
172 (100), 144 (10), 129 (22), 115 (52), 105 (71), 91 (95), 77 (96),
69 (54) and 51 (64).
(i) Ethyl 2,4-dioxo-6-phenylhex-5-enoate 7. Compound 7 was
prepared according to the literature procedure12 as yellow crys-
tals (76%), mp 82–83 ЊC (lit.,12 84 ЊC); νmax(Nujol)/cmϪ1 1725
(C᎐O), 1574, 1264, 1106, 982 and 778; δ (CDCl) 1.41 (3 H, t,
᎐
H
3
J 7, CH3CH2), 3.93 (0.2 H, s, OH, enol form), 4.31 (2 H, q,
J 7, CH2CH3), 6.55 (1.8 H, s, H-3, keto form), 6.67 (1 H, d, J
15.9, H-6), 7.40–7.44 (3 H, m, H-3Ј, -4Ј and -5), 7.55–7.59 (2 H,
m, H-2Ј and -6Ј) and 7.74 (1 H, d, J 15.9, H-5); m/z 246 (M+,
9%), 173 (100), 144 (8), 131 (62), 115 (60), 103 (74), 91 (32), 77
(84), 69 (69), 63 (24) and 51 (56).
(ii) Ethyl 5,6-dibromo-2,4-dioxo-6-phenylhexanoate 8. Com-
pound 8 was prepared according to the literature procedure12 as
yellowcrystals(90%), mp 106–107 ЊC (lit.,12 107 ЊC);νmax(Nujol)/
cmϪ1 1748 (C᎐O), 1643, 1257, 1131, 1011 and 816; δ (CDCl )
᎐
H
3
1.41 (3 H, t, J 7, CH3), 3.95 (0.2 H, s, OH, enol form, 4.40 (2 H,
q, J 7, CH2CH3), 4.97 (1 H, d, J 10.8, H-6), 5.39 (1 H, d, J 10.8,
H-5), 6.55 (1.8 H, s, H-3, keto form) and 7.26–7.46 (5 H, m, Ph);
m/z 407 (M+ + 1, 2%), 182 (6), 173 (36), 143 (31), 131 (37), 115
(68), 103 (57), 91 (13), 77 (75), 69 (100) and 51 (42).
Diels–Alder reactions—general procedure
The pyranone 3c–e (7 mmol) was dissolved in anhydrous tolu-
ene (4 cm3) and the diene 11b (9.3 mmol) was added. The mix-
ture was heated at 110 ЊC for 6 h. The residue was evaporated
and recrystallised from diethyl ether–light petroleum (bp 40–
60 ЊC) to yield the desired product 12 as a white powder.
4a-(tert-Butoxycarbonyl)-5-methoxy-2-phenyl-7-trimethyl-
(iii) Ethyl 4-oxo-6-phenyl-4H-pyran-2-carboxylate 3b. Com-
pound 3b was prepared according to the literature procedure12
as white crystals (65%), mp 127–128 ЊC (lit.,12 130 ЊC) (Found:
C, 69.1; H, 4.9. C14H14O2 requires C, 68.9; H, 4.9%);
νmax(Nujol)/cmϪ1 1735 (C᎐O), 1635 (C᎐O), 1614, 1255, 1093,
silyloxy-4a,5,8,8a-tetrahydro-4H-benzo[b]pyran-4-one
12a.
᎐
᎐
1058, 1016, 951, 923, 893 and 861; δH (CDCl3) 1.41 (3 H, t, J 7,
CH3), 4.40 (2 H, q, J 7, CH2CH3), 6.87 (1 H, d, J 2.2, H-5), 7.12
(1 H, d, J 2.2, H-3), 7.27–7.55 (3 H, m, H-3Ј, -4Ј and -5Ј), and
7.75–7.88 (2 H, m, H-2Ј and -6Ј); m/z 244 (M+, 27%), 216 (23),
188 (25), 171 (9), 144 (30), 112 (33), 102 (100), 77 (32) and 63
(24).
White powder (1.62 g, 52%), mp 125–127 ЊC (Found: C, 65.0;
H, 7.5. C24H32O6Si requires C, 64.8; H, 7.4%); νmax(Nujol)/cmϪ1
1730 (C᎐O), 1652 (C᎐O), 1598, 1571, 1334, 1251, 1216, 1187,
᎐
᎐
1162, 1077, 1017, 886 and 851; δH (CDCl3) 0.23 (9 H, s, OSiMe3),
1.48 (9 H, s, But), 2.50 (1 H, dd, J 19 and 4.4, H-8), 2.69 (1 H, d,
J 19, H-8), 3.23 (3 H, s, OMe), 4.56 (1 H, d, J 5.5, H-5), 5.27 (1
H, d, J 4, H-8a), 5.30 (1 H, d, J 5.5, H-6), 6.17 (1 H, s, H-3),
7.41 (2 H, m, H-3Ј and -5Ј), 7.43 (1 H, m, H-4Ј) and 7.74 (2 H,
m, H-2Ј and -6Ј); m/z 444 (M+, 1%), 343 (22), 223 (20), 157 (20),
141 (25), 105 (72), 89 (11), 77 (24), 73 (78) and 57 (100).
Synthesis of 2-(dimethylamino)methylene-3-oxobutanoates 10
—general procedure
Heating of an oxobutanoates 9 with equimolar quantities of
166
J. Chem. Soc., Perkin Trans. 1, 1997

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4a-(tert-Butoxycarbonyl)-5-methoxy-2-(4Ј-methoxyphenyl)-
7-trimethylsilyloxy-4a,5,8,8a-tetrahydro-4H-benzo[b]pyran-4-
one 12b. White powder (1.76 g, 53%), mp 163–165 ЊC (Found: C,
63.3; H, 7.2. C25H34O7Si requires C, 63.3; H, 7.2%); νmax(Nujol)/
cmϪ1 1731 (C᎐O), 1671 (C᎐O), 1594, 1569, 1510, 1426, 1350,
-6Љ), 128.0 (C-1Ј), 128.6 (C-2Ј and -6Ј), 129.5 (C-4Љ), 130.9
(C-3Љ and -5Љ), 141.2 (C-1Љ), 163.5 (C-4Ј), 165.8 (C-2), 170.7
(C᎐O), 171.8 (C᎐O) and 192.2 (C-4); m/z 493 (M+ + 1, 2%), 437
᎐
᎐
(2), 332 (5), 144 (8), 135 (10), 116 (9), 77 (24), 68 (18), 57 (100)
and 41 (43).
᎐
᎐
1307, 1254, 1237, 1218, 1189, 1121, 1080, 1030, 1000, 944, 905,
887 and 851; δH (CDCl3) 0.37 (9 H, s, OSiMe3), 1.45 (9 H, s, But),
2.47 (1 H, dd, J 18.6 and 3.6, H-8), 2.65 (1 H, d, J 18.6, H-8),
3.21 (3 H, s, 5-OMe), 3.83 (3 H, s, Ar-OMe), 4.54 (1 H, d, J 3.6,
H-5), 5.22–5.26 (2 H, m, H-8a and -6), 6.07 (1 H, s, H-3),
6.88 (2 H, d, J 8, H-3Ј and -5Ј) and 7.68 (2 H, d, J 8, H-2Ј and -6Ј);
m/z 474 (M+, 20%), 459 (5), 418 (8), 373 (75), 359 (12), 341 (13),
319 (21), 303 (12), 287 (10), 241 (10), 223 (53), 193 (22), 157
(60), 141 (55), 135 (77), 77 (51), 73 (75), 57 (100) and 41 (75).
4a-(Benzyloxycarbonyl)-5-methoxy-2-phenyl-7-trimethyl-
Desilylation of Diels–Alder adducts—general procedure
The tetrahydroflavone 12 (0.23 mmol) was dissolved in THF (5
cm3) and 36% aqueous HCl (1 drop) was added. The reaction
mixture was stirred for 44 h then saturated aqueous sodium
hydrogen carbonate (1 cm3) was added. The organic layer was
separated, dried (MgSO4) and evaporated in vacuo. Recrystal-
lisation from light petroleum gave the desired product 16.
4a-(tert-Butoxycarbonyl)-5-methoxy-2-phenyl-4a,5,6,7,8,8a-
hexahydro-4H-benzo[b]pyran-4,7-dione 16a. White powder (90
mg, 82%), mp 150–151 ЊC (Found: C, 67.8; H, 6.6. C21H24O6
silyloxy-4a,5,8,8a-tetrahydro-4H-benzo[b]pyran-4-one
12c.
White powder (1.77 g, 53%), mp 101–103 ЊC (Found: C,
68.1; H, 6.1. C27H30O6Si requires C, 67.8; H, 6.3%); νmax(Nujol)/
cmϪ1 1736 (C᎐O), 1654 (C᎐O), 1602, 1572, 1345, 1292, 1257,
requires C, 67.7; H, 6.5%); νmax(Nujol)/cmϪ1 1722 (C᎐O), 1656
᎐
(C᎐O), 1602, 1574, 1246, 1156, 1095, 1056, 1023, 978, 878 and
᎐
842; δH (CDCl3) 1.52 (9 H, s, But) 2.66 (1 H, dd, J 4.3 and 15.6,
H-8), 2.85 (2 H, d, J 3.2, H-6), 3.04 (1 H, dd, J 15.6 and 2.9,
H-8), 3.19 (3 H, s, OMe), 4.47–4.50 (1 H, m, H-5), 5.48–5.53 (1
H, m, H-8a), 6.18 (1 H, s, H-3), 7.40–7.50 (3 H, m, H-3Ј, -4Ј and
-5Ј) and 7.70–7.74 (2 H, m, H-2Ј and -6Ј); m/z 372 (M+, 16%), 315
(47), 299 (11), 286 (8), 271 (35), 257 (11), 241 (29), 230 (19), 217
(40), 199 (37), 177 (38) 170 (53), 153 (62), 147 (57), 138 (51), 125
(48), 105 (59), 102 (53), 95 (67), 85 (68), 77 (40), 68 (100), 57
(53), 53 (68) and 41 (65).
᎐
᎐
1229, 1196, 1092, 1074, 1051, 1022, 1004, 956, 890 and 872;
δH (CDCl3) 0.30 (9 H, s, OSiMe3), 2.48 (1 H, dd, J 18.7 and
4.5, H-8), 2.70 (1 H, d, J 18.7, H-8), 3.33 (3 H, s, OMe), 4.74 (1
H, d, J 5.3, H-5), 5.36 (2 H, s, CH2Ph), 5.30–5.42 (2 H, m, H-6
and -8a), 6.29 (1 H, s, H-3), 7.26–7.62 (8 H, m, Ar) and 7.81–
7.86 (2 H, m, H-2Ј and -6Ј); m/z 478 (M+, 9%), 463 (4), 379
(25), 343 (78), 325 (27), 317 (26), 311 (10), 271 (19), 241 (10),
223 (59), 200 (38), 172 (62), 157 (66), 141 (56), 121 (38), 115
(36), 105 (82), 91 (100), 77 (84), 73 (89), 65 (65), 59 (49) and
45 (38).
4a-(tert-Butoxycarbonyl)-5-methoxy-2-(4Ј-methoxyphenyl)-
4a,5,6,7,8,8a-hexahydro-4H-benzo[b]pyran-4,7-dione 16b. White
powder (54 mg, 58%), mp 139–40 ЊC (Found: C, 65.9: H, 6.7.
C22H26O7 requires C, 65.7; H, 6.5%); νmax(Nujol)/cmϪ1 1734
(C᎐O), 1645 (C᎐O), 1594, 1588, 1510, 1426, 1346, 1296, 1260,
4a-(tert-Butoxycarbonyl)-2-phenyl-4a,5,6,7,8,8a-hexahydro-
4H-benzo[b]pyran-4,7-dione 16c. Pyranone 3c (0.3 g, 1.10 mmol)
was dissolved in toluene (1 cm3) and diene 11a (0.93 g, 6.5
mmol) was added. The mixture was heated at 110 ЊC for 24 h.
The residue was treated with 0.01  HCl–THF (5 cm3), then
washed with saturated aqueous sodium hydrogen carbonate (2
cm3), dried (MgSO4) and the solvent evaporated. Purification
by flash column chromatography gave a white powder 16c (62
mg, 18%), mp 157–158 ЊC (Found: C, 70.1; H, 6.9. C20H22O5
᎐
᎐
1238, 1207, 1178, 1113, 1081, 1059, 1031, 979 and 878;
δH (CDCl3) 1.47 (9 H, s, But), 2.65 (1 H, dd, J 15.5 and 4.2, H-8),
2.85 (2 H, d, J 3.3, H-6), 3.02 (1 H, br d, J 15.7, H-8), 3.18 (3 H,
s, 5-OMe), 3.86 (3 H, s, 4Ј-OMe), 4.48–4.49 (1 H, m, H-5), 5.48–
5.52 (1 H, m, H-8a), 6.10 (1 H, s, H-3), 6.92 (2 H, d, H-3Ј and
-5Ј) and 7.62 (2 H, d, H-2Ј and -6Ј); δC(CDCl3) 27.9 (3 × CH3),
43.2 (C-8), 43.4 (C-6), 55.5 (4Ј-MeO), 58.6 (C-5), 58.3 (CMe3),
80.5 (C-8a), 81.6 (5-MeO), 83.6 (C-4a), 101.5 (C-3), 114.3
(C-3Ј and -5Ј), 124.4 (C-1Ј), 128.7 (C-2Ј and -6Ј), 162.8
(C-4Ј), 167.8 (C-2), 170.8 (CO2But), 189.2 (C-4) and 204.5
(C-7); m/z 402 (M+, 41%), 370 (10), 345 (37), 329 (13), 301 (13),
271 (30), 247 (25), 229 (21), 216 (11), 207 (20), 176 (100), 153
(17), 135 (68), 121 (49), 107 (32), 92 (37), 85 (52), 77 (53), 67
(41), 57 (40) and 42 (50).
requires C, 70.2; H, 6.8%); νmax(Nujol)/cmϪ1 1732 (C᎐O), 1726
᎐
(C᎐O), 1660 (C᎐O), 1595, 1573, 1341, 1296, 1272, 1249, 1151,
᎐
᎐
1083, 1046, 982 and 842; δH (CDCl3) 1.54 (9 H, s, But), 2.13–2.18
(1 H, m), 2.51–2.53 (2 H, m), 2.62–2.69 (2 H, m), 3.00 (1 H, ddd,
J 15.8, 3.9 and 2.0), 5.39 (1 H, d, J 3.4, H-5), 6.07 (1 H, s, H-3),
7.43–7.54 (3 H, m, H-3Ј, -4Ј and -5Ј) and 7.74 (2 H, d, H-2Ј and
-6Ј); m/z 342 (M+, 18%), 286 (3), 269 (9), 241 (23), 199 (23), 196
(52), 147 (64), 140 (71), 123 (63), 112 (57), 105 (87), 91 (22), 81
(86), 77 (63), 69 (88), 57 (92) and 41 (100).
tert-Butyl 5-ethoxycarbonyl-2-(4Ј-methoxyphenyl)-4-oxo-7-
phenyl-4,4a,5,6,7,7a-hexahydropyrano[2,3-c]pyrrole-4a-
Methoxy group elimination—general procedure
The tetrahydroflavone (0.23 mmol) was dissolved in dichloro-
methane (3 cm3) and TFAA (1 drop) was added. The reaction
mixture was stirred for 30 min then saturated aqueous sodium
hydrogen carbonate (1 cm3) was added. The organic layer was
separated, dried (MgSO4) and evaporated in vacuo. Recrystal-
lisation from light petroleum gave the desired product 17.
4a-(tert-Butoxycarbonyl)-2-phenyl-4a,7,8,8a-tetrahydro-4H-
benzo[b]pyran-4,7-dione 17a. White powder (61 mg, 78%), mp
135–137 ЊC (Found: C, 70.5; H, 5.9. C20H20O5 requires C, 70.6;
H, 5.9%); νmax(Nujol)/cmϪ1 1731 (C᎐O), 1687 (C᎐O), 1660
carboxylate 15. To a solution of pyranone 3d (0.1 g. 0.33 mmol)
and imine 13 (0.07 g, 0.36 mmol) in acetonitrile (10 cm3), tri-
ethylamine (0.035 g, 0.35 mmol) and lithium bromide (0.04 g,
0.46 mmol) were added. The reaction mixture was stirred for
8 h at room temperature, then was poured into saturated aqueous
ammonium chloride (6 cm3). The mixture was extracted with
diethyl ether (10 cm3) and the organic layer was dried (MgSO4),
evaporated and the residue was purified by flash chroma-
tography on silica, eluting with light petroleum–ethyl acetate
(1:1), to give the title compound 15 as a yellow powder (80 mg,
49%), mp 111 ЊC (Found: C, 68.3; H, 6.1: N, 2.9. C28H30NO7
᎐
᎐
(C᎐O), 1601, 1571, 1334, 1294, 1272, 1252, 1151, 1103, 1062,
᎐
1028, 1007, 991 and 834; δH (CDCl3) 1.52 (9 H, s, But), 2.73 (1 H,
dd, J 17.2 and 2.6, H-8), 3.12 (1 H, dd, J 17.2 and 3.9, H-8),
5.48–5.50 (1 H, m, H-8a), 6.18 (1 H, s, H-3), 6.24 (1 H, d, J
10.1, H-6), 6.64 (1 H, d, J 10.1, H-5), 7.42–7.54 (3 H, m, H-3Ј,
-4Ј and -5Ј) and 7.70–7.73 (2 H, m, H-2Ј and -6Ј); δC(CDCl3) 27.8
(3 × CH3), 40.0 (C-8), 58.7 (CMe3), 81.6 (C-8a), 84.3 (C-4a),
102.8 (C-3), 126.6 (C-2Ј and -6Ј), 128.8 (C-3Ј and -5Ј),
131.4 (C-4Ј), 131.8 (C-1Ј), 132.4 (C-7), 140.6 (C-5), 166.1
(C-2), 170 (CO2But), 187.2 (C-4) and 193.3 (C-7); m/z 341
(M+ + 1, 18%), 340 (M+, 7), 315 (15), 215 (38), 267 (20), 241
(21), 211 (19), 194 (28), 183 (13), 165 (13), 153 (24), 147 (57),
requires C, 68.3; H, 6.1: N 2.9%); νmax(Nujol)/cmϪ1 1688 (C᎐O),
᎐
1606 (C᎐O), 1585, 1536, 1510, 1308, 1254, 1192, 1176, 1114,
᎐
1090, 1022, 998, 913, 866, 837, 798, 775 and 698; δH (CDCl3) 1.32
(2 H, t, J 7, CH3CH2), 1.51 (9 H, s, But) 3.85 (3 H, s, MeO), 4.26
(2 H, q, J 7, CH2), 5.01 (1 H, d, J 5.7, H-7a), 5.14 (1 H, t, J 5.5,
H-7), 5.27 (1 H, d, J 3.7, H-5), 6.53 (1 H, s, H-3), 6.87–6.91 (2
H, m, H-3Ј and -5Ј), 7.17–7.28 (5 H, m, Ph) and 7.85–7.88 (2 H,
m, H-2Ј and -6Ј); δC(CDCl3) 13.6 (Me), 27.5 (3 × Me), 45.4
(CH2), 55.0 (C-5), 55.5 (MeO), 58.4 (C-7), 66.4 (C-7a), 82.9
(C-4a), 101.9 (C-3). 113.9 (C-3Ј and -5Ј), 126.4 (C-2Љ and
J. Chem. Soc., Perkin Trans. 1, 1997
167

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138 (58), 128 (29), 121 (61), 110 (33), 105 (80), 93 (48), 81 (76),
76 (91), 65 (55), 63 (65), 51 (71) and 42 (100).
1635, 1609, 1589, 1576, 1537, 1492, 1299, 1262, 1190, 1146,
1093, 1021, 993, 886 and 791; δH (CDCl3) 1.41 (3 H, t, J 7, CH3),
4.30 (1 H, s, H-2, keto form), 4.43 (2 H, q, J 7, CH2CH3), 6.64 (1
H, t, H-4Љ), 7.26–7.62 (4 H, m, H-3Ј, -4Ј, -5Ј and -5Љ), 7.82 (1 H,
d, J 7.1, H-6Љ), 8.04–8.08 (2 H, m, H-2Ј and -6Ј), 8.67–8.74 (1 H,
m, H-3Љ), 11.54 (1 H, s, NH) and 14.02 (1 H, s, OH, enol form);
m/z 311 (M+, 99%), 266 (10), 238 (10), 192 (22), 165 (99), 146
(72), 137 (48), 132 (35), 119 (99), 105 (78), 92 (57), 77 (100), 69
(70), 64 (69), 51 (62) and 41 (43).
4a-(tert-Butoxycarbonyl)-2-(4Ј-methoxyphenyl)-4a,7,8,8a-
tetrahydro-4H-benzo[b]pyran-4,7-dione 17b. White powder (42
mg, 49%), mp 128 ЊC (Found: C, 68.1; H, 6.1. C20H22O5 requires
C, 68.1; H, 6.0%); νmax(Nujol)/cmϪ1 1726 (C᎐O), 1686 (C᎐O),
᎐
᎐
1661 (C᎐O), 1606, 1588, 1565, 1511, 1425, 1326, 1312, 1299,
᎐
1272, 1239, 1183, 1155, 1120, 1102, 1064, 1036, 1004 and 898;
δH (CDCl3), 1.52 (9 H, s, But), 2.71 (1 H, dd, J 17.2 and 2.6, H-8),
3.10 (1 H, dd, J 17.2 and 4.1, H-8), 3.86 (3 H, s, OMe), 5.45–5.47
(1 H, m, H-8a), 6.10 (1 H, s, H-3), 6.23 (1 H, d, J 10.1, H-6),
6.64 (1 H, m, H-5), 6.92 (2 H, d, H-3Ј and -5) and 7.67 (2 H, d,
H-2Ј and -6Ј); δC(CDCl3) 27.9 (3 × CH3), 40.2 (C-8), 55.6
(OMe), 58.8 (CMe3), 78.7 (C-8a), 84.3 (C-4a), 100.3 (C-3),
114.3 (C-3Ј and -5Ј), 123.7 (C-1Ј), 128.7 (C-2Ј and -6Ј),
130.7 (C-6), 141.0 (C-5), 163.3 (C-4Ј), 166.5 (C-2), 170.1
(CO2But), 187.0 (C-4) and 193.7 (C-7); m/z 370 (M+, 36%), 355
(3), 315 (5), 297 (27), 270 (8), 240 (10), 194 (10), 176 (88), 149
(11), 135 (100), 121 (76), 107 (56), 92 (72), 77 (71), 69 (75), 65
(78), 57 (78), 43 (63) and 41 (80).
N-(2Љ-Ethoxycarbonylphenyl)-3-oxo-3-(4Ј-methoxyphenyl)-
propionamide 22b. From tetrahydroflavone 12b and ethyl
anthranilate 19a. White powder (30 mg, 22%), mp 110–111 ЊC
(Found: C, 66.8; H, 5.7; N, 4.1. C19H19NO5 requires C, 66.8; H,
5.6; N, 4.1%); νmax(Nujol)/cmϪ1 1688 (C᎐O), 1606, 1583, 1538,
᎐
1510, 1308, 1297, 1254, 1192, 1176, 1144, 1114, 1090, 1022, 998
and 914; δH (CDCl3) 1.29 (3 H, t, J 7, CH3), 3.9 (3 H, s, CH3),
4.19 (2 H, s, H-2, keto form), 4.30 (2 H, q, J 7, CH2CH3), 7.05 (2
H, d, J 8.8, H-3Ј and -5Ј), 7.20 (1 H, t, H-4Љ), 7.58 (1 H, t, H-5Љ),
7.90 (1 H, dd, J 1.5 and 7.9, H-6Љ), 7.99 (2 H, d, J 8.9, H-2Ј and
-6Ј) and 8.22 (1 H, d, J 8.2, H-3Љ); m/z 341 (M+, 61%), 285 (22),
239 (8), 195 (31), 177 (13), 165 (97), 150 (93), 135 (100), 119
(92), 107 (27), 92 (81), 77 (50), 65 (50) and 51 (20).
4-(2Ј-Cyanoanilino)benzoic acid 20b. From tetrahydroflavone
12b and anthranilonitrile 19b. White powder (62 mg, 65%), mp
182 ЊC (Found: C, 70.5; H, 4.2; N, 11.8. C14H10N2O2 requires C,
70.6; H, 4.2; N, 11.8%); νmax(Nujol)/cmϪ1 3326 (NH), 2222
4a-(tert-Butoxycarbonyl)-7-hydroxy-2-phenyl-4a,7,8,8a-
tetrahydro-4H-benzo[b]pyran-4-one 18. Pyranone 17a (0.17 g,
0.5 mmol) was dissolved in dry dichloromethane (10 cm3) and
sodium borohydride (0.19 g, 5 mmol) and silica gel (1.0 g) were
added. The reaction mixture was stirred for 24 h, then filtered,
washed with water (3 cm3), dried (MgSO4) and evaporated. The
residue was purified by column chromatography on silica, elut-
ing with light petroleum–ethyl acetate (2:1), to give 18 as a
colourless oil (0.16 g, 94%) (Found: C, 69.9; H, 6.7. C20H22O5
requires C, 70.2; H, 6.5%); νmax(Nujol)/cmϪ1 3431 (OH), 2977,
2932, 1729 (C᎐O), 1659 (C᎐O), 1603, 1573, 1494, 1450, 1392,
(CN), 1686 (C᎐O), 1596, 1521, 1316, 1286, 1255, 1207, 1170,
᎐
1034, 1010, 937 and 845; δH [(CD3)2SO] 7.05 (2 H, d, J 7.9, H-3
and -5), 7.07 (1 H, t, J 7.8, H-4Ј), 7.49 (1 H, t, J 7.8, H-5), 7.54 (1
H, d, J 8.0, H-6Ј), 7.59 (1 H, d, J 7.8, H-3Ј), 7.79 (2 H, d, J 7.9,
H-2, -6) and 8.76 (1 H, s, NH); m/z 238 (M+, 48%), 220 (47), 192
(52), 166 (37), 136 (38), 105 (57), 91 (91), 75 (74), 63 (58) and 50
(100).
N-(2Љ-Cyanophenyl)-3-oxo-3-phenylproprionamide 22c. From
tetrahydroflavone 12a and anthranilonitrile 19b. Red crystals
(27 mg, 28%), mp 129 ЊC (Found: C, 72.4; H, 4.8; N, 10.5.
C16H12N2O4 requires C, 72.4; H, 4.9; N, 10.6%); νmax(Nujol)/
cmϪ1 3271, 2229 (CN), 1697, 1669, 1581 and 1540; δH (CDCl3)
4.20 (2 H, s, H-2), 7.21 (1 H, m, H-4Љ), 7.46–7.66 (5 H, m, H-3Ј,
-4Ј, -5Ј, -5Љ and -6Љ), 8.06 (2 H, m, H-2Ј and -6Ј), 8.40 (1 H, d, J
8.5, H-3Љ) and 11.34 (1 H, br s, NH); m/z 264 (M+, 50%), 241
(30), 236 (32), 147 (57), 105 (80), 102 (53), 89 (40), 75 (100), 69
(95), 50 (89) and 43 (57).
᎐
᎐
1389, 1343, 1256, 1156, 1057, 982, 913 and 843; δH (CDCl3) 1.52
(9 H, s, But), 1.99–2.06 (2 H, m, H-8), 2.59–2.65 (1 H, m, H-7),
4.25 (1 H, br s, OH), 5.32–5.33 (1 H, m, H-8a), 5.72 (1 H, d, J
9.9, H-5), 6.12 (1 H, s, H-3), 6.18 (1 H, dd, J 9.9 and 4.0, H-6),
7.42–7.55 (3 H, m, H-3Ј, -4Ј and -5Ј) and 7.72–7.75 (2 H, m, H-2Ј
and -6Ј); m/z 345 (M+, 3%), 287 (5), 268 (8), 167 (8), 147 (47), 139
(27), 123 (28), 105 (54), 95 (28), 77 (60), 69 (45), 57 (100), 43 (52)
and 41 (80).
Reaction of reduced flavones 12 with anthranilic acid derivatives
19—general procedure
Tetrahydroflavone 12 (0.4 mmol) and anthranilonitrile 19b (0.4
mmol) or ethyl anthranilate 19a (0.4 mmol) were dissolved in
toluene (10 cm3) and PTSA (5–10 mg) was added. The reaction
mixture was refluxed for 3 h, then was cooled, diluted with
diethyl ether (15 cm3) and methanol (3 cm3) and extracted with
5% aqueous sodium hydrogen carbonate (4 cm3). The organic
layer was separated, dried (MgSO4), evaporated under reduced
pressure and triturated with diethyl ether to give a white powder
20. The residue was separated by column chromatography on
silica, eluting with light petroleum–ethyl acetate (1:1), to give the
products 21 and 22.
Acknowledgements
We thank the EPSRC Mass Spectrometry Service, Swansea, for
high resolution mass spectrometry. A grant from the National
Fund for Science and Research, Hungary (OTKA Project No.
W 015141) is gratefully appreciated.
References
1 P. W. Groundwater and K. R. H. Solomons, J. Chem. Soc., Perkin
Trans. 1, 1994, 173.
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Solomons, UK Pat. Appl., 9425409.1; PCT Appl., GB95/02948.
3 P. W. Groundwater, D. E. Hibbs, M. B. Hursthouse and M. Nyerges,
Heterocycles, 1996, 43, 745.
4-(2Ј-Ethoxycarbonylanilino)benzoic acid 20a. From tetra-
hydroflavone 12a and ethyl anthranilate 19a. White–green
powder (56 mg, 49%), mp 198–200 ЊC (Found: C, 67.3; H, 5.4;
N, 4.9. C16H15NO2 requires C, 67.4; H, 5.3; N, 4.9%);
νmax(Nujol)/cmϪ1 3291 (NH), 1686 (C᎐O), 1682 (C᎐O), 1594,
᎐
᎐
4 P. J. Cremins, S. T. Saengchantara and T. W. Wallace, Tetrahedron,
1987, 43, 3075.
5 Y.-G. Lee, K. Ishimaru, H. Iwasakai, K. Ohkata and K.-Y. Akiba,
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6 K. Ohkata, T. Kubo, K. Miyamoto, M. Ono, J. Yamamoto and
K.-Y. Akiba, Heterocycles, 1994, 38, 1483.
7 S. T. Saengchantara and T. W. Wallace, J. Chem. Soc., Perkin Trans.
1, 1986, 789; F. M. Dean, M. Al-Sattar and D. A. Smith, J. Chem.
Soc., Chem. Commun., 1983, 535; C. K. Ghosh, N. Tewari and
A. Bhattacharyya, Synthesis, 1984, 614; T. W. Wallace, I. Wardell,
K.-D. Li and S. R. Challand, J. Chem. Soc., Chem. Commun., 1991,
1707; S. J. Coutts and T. W. Wallace, Tetrahedron, 1994, 50, 11 755;
T. W. Wallace, I. Wardell, K.-D. Li, P. Leeming, A. D. Redhouse and
S. R. Challand, J. Chem. Soc., Perkin Trans. 1, 1995, 2293.
1569, 1529, 1509, 1421, 1310, 1294, 1261, 1237, 1178, 1161,
1114, 1087, 1016, 929 and 867; δH [(CD3)2SO] 1.29 (3 H, t, J 7,
CH3), 4.28 (2 H, q, J 7, CH2), 6.97 (1 H, t, J 7.9, H-4Ј), 7.22 (2
H, d, J 8.5, H-3 and -5), 7.44–7.53 (2 H, m, H-5Ј and -6Ј), 7.84
(2 H, d, J 8.5, H-2 and -6), 7.91 (1 H, d, J 7.9, H-3Ј), 9.41 (1 H,
s, NH) and 12.56 (1 H, br s, CO2H); m/z 285 (M+, 100)%), 239
(77), 221 (41), 195 (84), 167 (84), 139 (43), 115 (15), 97 (15), 92
(64), 77 (48), 65 (71), 51 (52), 45 (82) and 43 (53).
N-(2Љ-Ethoxycarbonylphenyl)-3-oxo-3-phenylpropionamide
22a. From tetrahydroflavone 12a and ethyl anthranilate 19a.
Colourless oil (21 mg, 17%) (HRMS: calc. for C18H17NO4,
311.1158. Found M, 311.1158); νmax(Nujol)/cmϪ1 1689 (C᎐O),
᎐
168
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Paper 6/02245E
Received 1st April 1996
Accepted 27th August 1996
J. Chem. Soc., Perkin Trans. 1, 1997
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