Reactions of 2,3-dihydrofuro[3,2-c]coumarin-3-one with aromatic amines

Article abstract of DOI:10.1007/s11172-009-0260-7

2,3-Dihydrofuro[3,2- c]coumarin-3-one reacts with aromatic amines in two pathways, depending on the solvent. The reactions in ethanol afford its enamines, while the use of acetic acid favors the formation of enamines of the 2,3-dihydrofuro[3,2-c]coumarin-3-one dimer. Electronic absorption spectroscopy in different solvents revealed that the enamines obtained can undergo tautomeric transformations. The product of a reaction of 2,3-dihydrofuro-[3,2-c]coumarin- 3-one with 4-bromoaniline exists in the enamine form (X-ray diffraction data).

Full text of DOI:10.1007/s11172-009-0260-7

Russian Chemical Bulletin, International Edition, Vol. 58, No. 9, pp. 1908—1914, September, 2009
1908
Reactions of 2,3ꢀdihydrofuro[3,2ꢀc]coumarinꢀ3ꢀone
with aromatic amines
N. A. Kondratova,a O. N. Kazheva,b G. G. Aleksandrov,c O. A. D´yachenko,b and V. F. Travena
aD. I. Mendeleev University of Chemical Technology of Russia,
3 Miusskaya pl., 125047 Moscow, Russian Federation.
Eꢀmail: traven@muctr.ru
bInstitute of Problems of Chemical Physics, Russian Academy of Sciences,
1 prosp. Akad. Semenova, 142432 Chernogolovka, Moscow Region, Russian Federation
cN. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation
2,3ꢀDihydrofuro[3,2ꢀc]coumarinꢀ3ꢀone reacts with aromatic amines in two pathways,
depending on the solvent. The reactions in ethanol afford its enamines, while the use of acetic
acid favors the formation of enamines of the 2,3ꢀdihydrofuro[3,2ꢀc]coumarinꢀ3ꢀone dimer.
Electronic absorption spectroscopy in different solvents revealed that the enamines obtained
can undergo tautomeric transformations. The product of a reaction of 2,3ꢀdihydrofuroꢀ
[3,2ꢀc]coumarinꢀ3ꢀone with 4ꢀbromoaniline exists in the enamine form (Xꢀray diffraction data).
Key words: furocoumarinones, imines, enamines, tautomerism, dimerization, Xꢀray
diffraction analysis, electronic absorption spectra.
Aromatic imines tend to undergo various transformaꢀ
Literature data on tautomeric transformations of
furocoumarinone imines and hydrazones are lacking. At
the same time, such compounds are of interest because of
intense fluorescence of many hydroxyꢀ and aminoꢀ
coumarins.5,6 Earlier, we have studied condensation reacꢀ
tions of 2,3ꢀdihydrofuro[3,2ꢀc]coumarinꢀ3ꢀone (1)7 with
aromatic aldehydes8 and found that the condensation
products exhibit pronounced fluorescence.
Interest in reactions of dihydrofurocoumarinone 1 is
also due to its structural analogy with βꢀdicarbonyl comꢀ
pounds.5,9 The resonance structures (Scheme 1) show a
particular electron density distribution in its molecule,
which determines the distinctive features of its reactivity.
tions between different isomers. Some of them are tautoꢀ
mers, while others are geometric isomers about the C=N
bond. These transformations can be initiated by various
factors (solvent, temperature, or irradiation) and can be
of interest for design of novel sensor structures.1—3 An
example of isomerization accompanied by considerable
changes in fluorescence is the previously studied4 E—Z
isomerization of 8ꢀ[(9Hꢀfluorenꢀ2ꢀylimino)methyl]ꢀ
7ꢀhydroxyꢀ4ꢀmethylꢀ2Hꢀ1ꢀbenzopyranꢀ2ꢀone in acetoꢀ
nitrile.
Scheme 1
Results and Discussion
In the present work, we studied reactions of ketone 1
with various aromatic amines. Prolonged heating of keꢀ
tone 1 with an excess of an aromatic amine in ethanol
afforded derivatives 2 (Scheme 2).
AdNꢀE reactions of ketone 1 with aromatic amines
(Nꢀnucleophiles) should give condensation products 2 in
the imino form. However, the compounds obtained are
not imines (1H NMR data). The absence of signals at δ 5
is indicative of the absence of two protons at the C(4a)
atom and, consequently, of aromatization of the dihydroꢀ
furan ring giving rise to enamines 2.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1848—1853, September, 2009.
1066ꢀ5285/09/5809ꢀ1908 © 2009 Springer Science+Business Media, Inc.

Reactions of furocoumarins with aromatic amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1909
Scheme 2
Table 1. PM3ꢀcalculated enthalpies of formation (H° )
f
of the tautomeric (imine and enamine) forms of comꢀ
pounds 2a—h in the presence (I) and in the absence of
intramolecular hydrogen bonding (II)
Tautomer
–H° /kcal mol–1
f
Imine
Enamine
(imine)
I
II
2a
2b
2c
2d
2e
2f
20.36
58.11
12.79
29.87
29.46
56.11
64.03
29.81
24.47
61.37
16.08
33.84
33.82
61.33
67.82
34.20
20.39
58.04
12.81
33.09
30.73
58.00
67.15
30.73
2g
2h
the expected enamines 2 did not form. Instead, we obꢀ
tained compounds 3, which are amino derivatives of 2,3´ꢀ
bi(2Hꢀfuro[3,2ꢀc]chromene)ꢀ3,4,4´ꢀtrione, a dimer of
2,3ꢀdihydrofuro[3,2ꢀc]coumarinꢀ3ꢀone (Scheme 4).
Earlier,3 we have demonstrated that compound 1 tends
to undergo selfꢀcondensation leading to dimer 4. For this
reason, one could assume that reactions of ketone 1 with
some aromatic amines would proceed through the formaꢀ
tion of intermediate 2,3´ꢀbi(2Hꢀfuro[3,2ꢀc]chromene)ꢀ
3,4,4´ꢀtrione (4) followed by the same AdNꢀE reaction
with an appropriate amine as that in the case of ketone 1
(Scheme 5, pathway a).
To verify this assumption, we dissolved prepared dimer
4 in a mixture of acetic acid and DMSO and refluxed the
resulting solution with 4ꢀbromoaniline for 4 h. However,
after the reaction mixture was cooled, the expected
3ꢀ(4ꢀbromophenylamino)ꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]chromene)ꢀ
4,4´ꢀdione (3c) was not detected; instead, the starting
reagents were recovered.
(enamine)
R = H (a), 4ꢀОMe (b), 4ꢀBr (c), 4ꢀMe (d), 4ꢀNO2 (e), 2ꢀOMe (f),
4ꢀF (g), 3ꢀNO2 (h)
The formation of enamines 2 is also confirmed by
other signals in the 1H NMR spectrum. For instance, the
presence of a narrow singlet at δ 8.08—8.40 is due to the
C(4a)H proton of the furan ring; the strong downfield
shift of this signal agrees with the aromaticity of the furan
ring. The broadened singlet at δ 7.27—8.90 (depending on
the structure of the starting aromatic amine) should be
assigned to the amino group NH in the enamine form.
The preferred formation of compounds 2a—h as enamꢀ
ine tautomers was confirmed by quantumꢀchemical calꢀ
culations. We calculated their enthalpies of formation
making allowance for hydrogen bonding between the
amino NH atom and the carbonyl O atom of the lactone
fragment and without this bonding. According to the data
obtained (Table 1), the enamine form is more stable than
the imine form for most of compounds 2, even in the
absence of the above hydrogen bonding (Scheme 3).
The formation of compounds 3 can follow an alternaꢀ
tive reaction sequence involving the initial formation of
an imino derivative of 2,3ꢀdihydrofuro[3,2ꢀc]coumarinꢀ
3ꢀone 2 and its reaction in the enamine form with another
molecule of compound 1 at position 4a (Scheme 5, pathꢀ
way b).
Scheme 3
To verify the possibility of this pathway, we dissolved
prepared 3ꢀ(4ꢀbromophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin
2c in acetic acid and slightly refluxed with an excess of
ketone 1. The reaction gave the expected 3ꢀ(4ꢀbromoꢀ
phenylamino)ꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]coumarin) 3c.
Therefore, the formation of compound 3 proceeds
through the formation of enamine 2 rather than dimer 4.
In a reaction with ketone 1, enamine 2 acts as a stronger
Cꢀnucleophile than the enol (and very minor8) form of
the starting ketone.
Reactions of ketone 1 with excesses of aromatic amines
in acetic acid yield different products. With aniline and
4ꢀnitroaniline as the amino components, the major prodꢀ
ucts were enamines 2. From other substituted anilines,
As noted above, the reactions of ketone 1 with aniline
and 4ꢀnitroaniline in acetic acid do not yield comꢀ

1910
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Kondratova et al.
Scheme 4
R = H (a), 4ꢀBr (c), 4ꢀMe (d), 4ꢀNO2 (e), 4ꢀF (g)
Scheme 5
unsubstituted aniline, the absence of product 3a is diffiꢀ
cult to explain since compound 2a is well soluble in acetic
acid and was obtained in good yield when a great excess
of the amine was used.
pounds 3. The formation of product 3e from compound
2e is most likely precluded by its low solubility in acetic
acid: compound 2e precipitates during the course of the
reaction, thus leaving the reaction zone. In the case of

Reactions of furocoumarins with aromatic amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1911
N atom in compound 2c is sp2ꢀhybridized because of the
conjugation of its lone electron pair with the πꢀsystems of
the phenyl and furan fragments. The C(4)—C(5) bond
is shortened (1.357 Å). It can be seen in Table 3 that
the C(4)—C(5) bond is even shorter than the double
C(3)=C(7) bond (1.362(3) Å) in the lactone ring of couꢀ
marin. This provides unambiguous evidence for the aroꢀ
matization of the fiveꢀmembered ring in compounds 2.
In the crystal structure of compound 2c, one crystalꢀ
lographically independent molecule occupies the general
position (see Fig. 2). The molecule is nearly planar: the
largest deviation from the meanꢀsquare plane of all nonꢀ
hydrogen atoms is 0.10 Å (O(2)). The deviation of the
N(1) atom from the plane H(1)C(4)C(14) is 0.007 Å. The
dihedral angle between the planes of the benzene ring
C(14)C(15)...C(19) and the furochromene tricyclic sysꢀ
tem O(1)C(2)C(3)...C(13) is 3.6°.
Table 2. Experimental parameters of the electronic absorption
spectra of compounds 2a—h
Compound
λ
max/nm (log ε)
CCl4
EtOH
DMF
2а
2b
2c
2d
2e
2f
357 (4.03)
365 (4.09)
358 (3.92)
360 (4.06)
370 (4.32)
365 (3.92)
357 (3.87)
347 (4.14)
354 (4.08)
365 (4.37)
352 (3.75)
355 (3.92)
367 (4.32)
361 (3.89)
355 (3.60)
339 (4.11)
353 (4.00)
364 (3.94)
353 (3.93)
354 (3.93)
381 (4.43)
359 (3.92)
354 (3.86)
336 (4.10)
2g
2h
A
In contrast to the (2Z)ꢀ2ꢀ[4´ꢀ(dimethylamino)benzylꢀ
idene]ꢀ4Hꢀfuro[3,2ꢀc]chromeneꢀ3,4(2H)ꢀdione8 strucꢀ
ture characterized by regular stacks, the crystal structure
of compound 2c consists of layers of its molecules united
0.4
1
2
3
0.3
0.2
0.1
4
5
c
300
350
400
450
λ/nm
Fig. 1. Electronic absorption spectra of compound 2h in (1) CCl4,
(2) CCl4—DMF (3 : 1), (3) CCl4—DMF (1 : 1), (4) CCl4—DMF
(1 : 3), and (5) DMF.
0
a
The electronic absorption spectra of compounds 2 in
various solvents show that the peak wavelengths differ
only slightly (Table 2). The bathochromic shift of the
longerꢀwavelength absorption peak of compounds 2 when
moving from DMF to CCl4 is most likely due to an inꢀ
creased contribution from the enamine form to its strucꢀ
ture, which can be stabilized in a nonpolar solvent by a
hydrogen bond between the NH group of the enamine
and the carbonyl O atom of the lactone fragment. The
equilibrium between the imino and enamine forms is
confirmed by an isosbestic point arising when moving
from a polar solvent to a nonpolar one (see Fig. 1).
Fig. 3. Crystal structure 2c.
N(1´)
H(1´)
C(15´)
In conclusion, note that the enamine form of comꢀ
pounds 2 was confirmed by Xꢀray diffraction (Fig. 2). The
O(2´)
H(15´)
H(15)
O(2)
O(6)
H(1)
C(19)
C(10)
C(9)
C(7)
C(18)
C(17)
C(15)
Br(1)
C(5)
C(4)
C(11)
C(12)
C(8)
N(1)
N(1)
C(14)
C(13)
C(16)
C(3)
C(2)
O(2)
C(15)
H(1)
O(1)
Fig. 4. Shortened intermolecular contacts in the dimeric
associate (2c)2.
Fig. 2. Molecular structure 2c with atomic numbering.

1912
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Kondratova et al.
Table 3. Selected bond lengths (d) and bond angles (ω) in strucꢀ
ture 2c (Xꢀray diffraction data)
into centrosymmetric dimers through shortened intermoꢀ
lecular contacts O...O and hydrogen bonds O...H—C
and O...H—N: O(2)...O(2´), 2.850(3) Å; O(2)...H(1´),
2.55(3) Å; O(2)...H(15´), 2.45(2) Å (the sums of the
van der Waals radii for these pairs of atoms are 3.04 (O...O)
and 2.72 Å (O...H))10 (Figs 3, 4). In adjacent layers, the
molecules have different orientations making a dihedral
angle of 63.4° between their meanꢀsquare planes.
Parameter
Value
Parameter
Bond
Value
Bond
d/Å
d/Å
O(2)—C(2)
N(1)—C(4)
N(1)—C(14)
N(1)—H(1)
C(2)—C(3)
C(3)—C(7)
Angle
1.209(3) C(3)—C(4)
1.382(3) C(4)—C(5)
1.383(3) C(5)—O(6)
0.80(3) C(5)—H(5)
1.434(3) O(6)—C(7)
1.362(3) C(7)—C(8)
ω/deg Angle
1.427(3)
1.357(3)
1.398(3)
0.90(3)
1.348(3)
1.418(3)
ω/deg
Experimental
1H NMR spectra were recorded on a Bruker WPꢀ200ꢀSY
spectrometer (200 MHz) in DMSOꢀd6 and CDCl3 with Me4Si
as the internal standard. Mass spectra were measured on a
Finnigan MAT SSQꢀ710 mass spectrometer (EI, 70 eV). The
course of the reactions was monitored, and the purity of the
compounds obtained was checked, by TLC on Silufol UVꢀ254
plates in the following solvent systems: (A) chloroform—acetone
(16 : 1), (B) chloroform—acetone (5 : 1), and (C) hexane—
acetone (2 : 1). Electronic absorption spectra were recorded on
an APEL PDꢀ303UV spectrometer. A cell with a solvent was
used as a reference cell.
C(4)—N(1)—C(14) 129.6(2) N(1)—C(4)—C(3) 122.5(2)
C(4)—N(1)—H(1) 114(2)
C(14)—N(1)—H(1)117(2)
C(4)—C(5)—O(6) 110.9(2)
N(1)—C(14)—C(15) 134(2)
O(2)—C(2)—O(1) 117.8(2) C(4)—C(5)—H(5) 115(2)
O(2)—C(2)—C(3) 126.4(2) O(6)—C(5)—H(5) 105.8(2)
O(1)—C(2)—C(3) 115.8(2) C(7)—O(6)—C(5) 110.5(2)
C(7)—C(3)—C(4) 107.7(2) O(6)—C(7)—C(3) 125.5(2)
C(7)—C(3)—C(2) 120.3(2) O(6)—C(7)—C(8) 124.0(2)
C(4)—C(3)—C(2) 132.0(2) C(3)—C(7)—C(8) 124.5(2)
C(5)—C(4)—N(1) 132.4(2) N(1)—C(14)—C(19) 117.8(2)
C(5)—C(4)—C(3) 105.0(2)
Quantumꢀchemical semiempirical PM3 calculations were
performed with the Hyper Chem 6.0 program package. For preꢀ
liminary geometry optimization, the molecular mechanics
method (MM+ version) was employed.
A single crystal of compound 2c was obtained by crystallizaꢀ
tion from ethanol.
δ: 6.86—6.88 (m, 1 H, H(4´)); 7.12 (d, 2 H, H(2´), H(6´),
J2´,6´ = 6 Hz); 7.26—7.39 (m, 2 H, H(3´), H(5´)); 7.40—7.60
(m, 2 H, H(6), H(8)); 7.49 (s, 1 H, NH); 7.64—7.66 (m, 1 H,
H(7)); 7.95 (d, 1 H, H(5), J5,6 = 8 Hz); 8.22 (s, 1 H, CH).
MS, m/z (Irel (%)): 278 [M + 1]+ (100), 277 [M]+ (80), 276
[M – 1]+ (88). Found (%): C, 73.61; H, 4.02; N, 5.25. C17H11NO3.
Calculated (%): C, 73.64; H, 4.00; N, 5.05.
Singleꢀcrystal Xꢀray diffraction was carried out on a Bruker
SMART APEX2 CCD diffractometer (MoꢀKα radiation,
graphite monochromator) at 200 K. The crystal structure was
solved by the direct methods followed by difference Fourier
syntheses with the SHELXSꢀ97 program.11 The structure was
refined by the leastꢀsquares method in the anisotropic fullꢀ
matrix approximation for all nonꢀhydrogen atoms with the
SHELXLꢀ97 program.12 An absorption correction was applied
with the APEX2 program.13 The coordinates of the hydrogen
atoms were determined experimentally and refined isotropically.
Selected crystallographic parameters and the data collection
statistics for compound 2c: C17H10BrNO3, M = 356.17, monoꢀ
clinic crystals, space group P21/c, a = 17.442(2) Å, b = 5.570(2) Å,
3ꢀ(4ꢀMethoxyphenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2b).
1
Yield 0.2 g (43.8%), gray needles, m.p. 184—186 °C. H NMR
(DMSOꢀd6), δ: 3.72 (s, 3 H, OMe); 6.88 (d, 2 H, H(3´), H(5´),
J3´,2´ = 8 Hz); 7.12 (d, 2 H, H(2´), H(6´), J2´,3´ = 8 Hz); 7.27
(s, 1 H, NH); 7.40—7.60 (m, 3 H, H(6), H(7), H(8)); 7.63—7.65
(m, 1 H, H(7)); 7.94 (d, 1 H, H(5), J5,6 = 8 Hz); 8.08 (s, 1 H,
CH). MS, m/z (Irel (%)): 308 [M + 1]+• (100). Found (%):
C, 71.00; H, 3.90; N, 4.60. C18H13NO4. Calculated (%): C, 70.35;
H, 4.26; N, 4.56.
3ꢀ(4ꢀBromophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2c). Yield
0.26 g (48%), yellow needles, m.p. 237—238 °C. 1H NMR
(DMSOꢀd6), δ: 7.12 (d, 2 H, H(3´), H(5´), J3´,2´ = 10 Hz); 7.38
(d, 2 H, H(2´), H(6´), J2´,3´ = 8 Hz); 7.40—7.70 (m, 3 H, H(6),
H(7), H(8)); 7.74 (s, 1 H, NH); 7.92 (d, 1 H, H(5), J5,6 = 6 Hz);
8.20 (s, 1 H, CH). MS, m/z (Irel (%)): 358 [81Br M + 1]+• (100),
356 [79Br M + 1]+• (98). Found (%): C, 56.92; H, 2.80; N, 3.80.
C17H10BrNO3. Calculated (%): C, 57.33; H, 2.83; N, 3.93.
3ꢀ(pꢀToluidino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2d). Yield 0.18 g
(42%), orange needles, m.p. 167—168 °C. 1H NMR (DMSOꢀd6),
δ: 2.24 (s, 3 H, Me); 7.03 (d, 2 H, H(3´), H(5´), J3´,2´ = 8 Hz);
7.10 (d, 2 H, H(2´), H(4´), J2´,3´ = 8 Hz); 7.34 (s, 1 H, NH);
7.40—7.58 (m, 2 H, H(6), H(8)); 7.64—7.67 (m, 1 H, H(7));
7.95 (d, 1 H, H(5), J5,6 = 8 Hz); 8.16 (s, 1 H, CH). MS, m/z
(Irel (%)): 292 [M + 1]+• (100). Found (%): C, 74.01; H, 4.40;
N, 4.83. C18H13NO3. Calculated (%): C, 74.22; H, 4.50; N, 4.81.
3ꢀ(4ꢀNitrophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2e). Yield
0.2 g (42%), orange needles, m.p. 310—312 °C. 1H NMR
(DMSOꢀd6), δ: 7.10 (d, 2 H, H(2´), H(6´), J2´,3´ = 10 Hz);
3
c = 15.511(2) Å, β = 115.634(1)°, V = 1358.6(5) Å , Z = 4,
dcalc = 1.74 g cm–3, μ = 3.038 mm–1, (2θ)max = 58.82°, the number
of measured reflections 9401, the number of independent reflecꢀ
tions 3399, the number of parameters refined 239, R = 0.041 for
2392 reflections with F0 > 4σ(F0).
The bond lengths and bond angles are given in Table 3.
Synthesis of 3ꢀaryliminoꢀ2,3ꢀdihydrofuro[3,2ꢀc]coumarins
2a—h (general procedure). 2,3ꢀDihydrofuro[3,2ꢀc]coumarinꢀ
3ꢀone7 (0.3 g, 1.5 mmol) was dissolved in boiling ethanol
(35 mL). Then a solution of an appropriate aromatic amine
(1.65 mmol) in ethanol (5 mL) was added. The resulting soluꢀ
tion turned orange. The course of the reaction was monitored by
TLC. The heating time was varied from 2 to 2.5 h, depending on
the amine structure. On cooling, the precipitate that formed was
filtered off, washed with ethanol, dried, and recrystallized from
96% ethanol or glacial acetic acid.
3ꢀPhenylaminoꢀ4Hꢀfuro[3,2ꢀc]coumarin (2a). Yield 0.18 g
(43.4%), yellow needles, m.p. 193—194 °C. 1H NMR (DMSOꢀd6),

Reactions of furocoumarins with aromatic amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1913
H(5″), J3 ,2″ = 8 Hz); 6.89 (d, 2 H, H(2″), H(4″), J ″ = 8 Hz);
7.40—7.60 (m, 3 H, H(6), H(8)); 7.66—7.67 (m, 1 H, H(7));
7.99 (d, 1 H, H(5), J5,6 = 8 Hz); 8.08 (d, 2 H, H(3´), H(5´),
J3´,2´ = 10 Hz); 8.39 (s, 1 H, CH); 8.87 (s, 1 H, NH). MS, m/z
(Irel (%)): 323 [M + 1]+• (100). Found (%): C, 63.01; H, 3.00;
N, 8.72. C17H10N2O5. Calculated (%): C, 63.36; H, 3.13;
N, 8.69.
″
″
2 ,3
7.42—7.60 (m, 4 H, H(6), H(8), H(6´), H(8´)); 7.66—7.70 (m,
2 H, H(7), H(7´)); 7.75 (s, 1 H, NH); 8.02 (d, 2 H, H(5),
H(5´), J5,6 = 6 Hz); 8.34 (s, 1 H, CH). MS, m/z (Irel (%)): 476
[M + 1]+• (100). Found (%): C, 73.35; H, 3.64; N, 2.82.
C29H17NO6. Calculated (%): C, 73.26; H, 3.60; N, 2.95.
3ꢀ(4ꢀFluorophenyl)ꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]chromene)ꢀ
4,4´ꢀdione (3g). Yield 0.07 g (19%), light brown crystals,
m.p. 232—233 °C. 1H NMR (DMSOꢀd6), δ: 6.70—6.96 (m,
4 H, H(2″), H(3″), H(5″), H(6″)); 7.40—7.60 (m, 6 H, H(6),
H(8), H(6´), H(8´)); 7.64—7.68 (m, 2 H, H(7), H(7´)); 7.83 (s,
1 H, NH); 7.99 (s, 2 H, H(5), H(5´), J5,6 = 8 Hz); 8.38 (s, 1 H,
CH). MS, m/z (Irel (%)): 480 [M + 1]+• (100). Found (%):
C, 70.25; H, 3.02; N, 2.90. C28H14FNO6. Calculated (%):
C, 70.15; H, 2.94; N, 2.92.
Synthesis of 2,3´ꢀbi(2Hꢀfuro[3,2ꢀc]chromene)ꢀ3,4,4´ꢀtrione
4. Ketone 1 (0.93 g, 4.6 mmol) was refluxed in glacial acetic acid
(12 mL) in the presence of conc. HCl (6 mL) for 3 h. The dimer
obtained was filtered off, washed with hot acetone, and recrysꢀ
tallized from DMSO. The yield was 0.71 g (80%), dark claret
crystals, m.p. 310 °C (decomp.). 1H NMR (DMSOꢀd6), δ: 6.50
(s, 1 H, H(2)); 7.30—7.60 (m, 4 H, H(8), H(6), H(8´), H(6´));
7.70—8.20 (m, 4 H, H(9), H(7), H(9´), H(7´)); 8.52 (s, 1 H,
H(2´)). MS, m/z (Irel (%)): 387 [M + 1]+• (100). Found (%):
C, 67.77; H, 2.60. C22H10O7. Calculated (%): C, 68.40; H, 2.61.
Synthesis of compound 3c from 3ꢀ(4ꢀbromophenylamino)ꢀ
4Hꢀfuro[3,2ꢀc]coumarin 2c. Compound 2c (0.36 g, 1.00 mmol)
was dissolved in boiling acetic acid. Then ketone 1 (0.2 g,
1.00 mmol) was added and the reaction mixture was refluxed
for 2 h. On cooling, the precipitate that formed was filtered
off, washed with acetic acid, dried, and recrystallized from
acetic acid or 96% ethanol. Yield 0.21 g (40%), white crystals,
m.p. 234—235 °C.
3ꢀ(2ꢀMethoxyphenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2f).
1
Yield 0.19 g (41%), white crystals, m.p. 243—244 °C. H NMR
(DMSOꢀd6), δ: 6.84—7.15 (m, 4 H, H(3´), H(4´), H(5´), H(6´));
7.40—7.70 (m, 3 H, H(6), H(7), H(8)); 7.60 (s, 1 H, NH);
7.97 (d, 1 H, H(5), J5,6 = 8 Hz); 8.36 (s, 1 H, CH). MS,
m/z (Irel (%)): 308 [M + 1]+• (100). Found (%): C, 70.94;
H, 4.34; N, 4.42. C18H13NO4. Calculated (%): C, 70.35; H, 4.26;
N, 4.56.
3ꢀ(4ꢀFluorophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2g). Yield
1
0.2 g (46%), bright green needles, m.p. 200—201 °C. H NMR
(DMSOꢀd6), δ: 7.00—7.22 (m, 4 H, H(2´), H(3´), H(5´), H(6´));
7.40—7.60 (m, 2 H, H(6), H(8)); 7.52 (s, 1 H, NH); 7.63—7.65
(m, 1 H, H(7)); 7.94 (d, 1 H, H(5), J5,6 = 8 Hz); 8.15 (s, 1 H,
CH). MS, m/z (Irel (%)): 296 [M + 1]+• (100). Found (%):
C, 69.36; H, 3.52; N, 4.73. C17H10FNO3. Calculated (%):
C, 69.15; H, 3.41; N, 4.74.
3ꢀ(3ꢀNitrophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2h). Yield
0.21 g (43%), yellow needles, m.p. 249—250 °C. 1H NMR
(DMSOꢀd6), δ: 7.42—7.72 (m, 6 H, H(4´), H(5´), H(6´), H(6),
H(7), H(8)); 7.88 (s, 1 H, H(2´)); 7.98 (d, 1 H, H(5), J5,6 = 8 Hz);
8.34 (s, 1 H, CH); 8.36 (s, 1 H, NH). MS, m/z (Irel (%)): 323
[M + 1]+• (100). Found (%): C, 63.45; H, 2.98; N, 8.54
C17H10N2O5. Calculated (%): C, 63.36; H, 3.13; N, 8.69.
Synthesis of 3ꢀarylaminoꢀ4Hꢀfuro[3,2ꢀc]coumarins 2a,e
in acetic acid. A solution of an appropriate aromatic amine
(1.64 mmol) in acetic acid (2 mL) was added to a hot solution of
ketone 1 (1.5 mmol) in glacial acetic acid (3 mL). The reaction
mixture was slightly refluxed for ~1 h. The solution turned dark
claret. The course of the reaction was monitored by TLC. On
cooling, the precipitate that formed was filtered off, washed
with acetic acid, dried, and recrystallized from acetic acid or
96% ethanol.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ
90016ꢀBel_a).
3ꢀPhenylaminoꢀ4Hꢀfuro[3,2ꢀc]coumarin (2a). Yield 0.19 g
(45%), pale yellow needles, m.p. 193—194 °C.
References
3ꢀ(4ꢀNitrophenylamino)ꢀ4Hꢀfuro[3,2ꢀc]coumarin (2e). Yield
1. R. N. Nurmukhametov, Pogloshchenie i lyuminestsentsiya
aromaticheskikh soedinenii [Absorption and Luminescence
of Aromatic Compounds], Khimiya, Moscow, 1971, 216 (in
Russian).
2. E. N. Shepelenko, V. A. Bren´, I. L. Minkin, Khim. Geterotsikl.
Soedin., 1989, 5, 591 [Chem. Heterocycl. Compd. (Engl.
Transl.), 1989, 5].
3. D. K. Smith, J. Chem. Educ., 2005, 82, 393.
4. V. F. Traven, V. S. Miroshnikov, A. S. Pavlov, I. V. Ivanov,
A. V. Panov, T. A. Chibisova, Mendeleev Commun., 2007,
17, 88.
5. A. V. Manaev, T. A. Chibisova, V. F. Traven, Izv. Akad.
Nauk, Ser. Khim., 2006, 2144 [Russ. Chem. Bull., Int. Ed.,
2006, 55, 2226].
0.2 g (42%), orange needles, m.p. 310—312 °C.
Synthesis of 3ꢀarylaminoꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]chromene)ꢀ
4,4´ꢀdiones 3c, 3d, and 3g in acetic acid. Reactions of ketone 1
with 4ꢀbromoaniline, pꢀtoluidine, and 4ꢀfluoroaniline in acetic
acid were carried out as described for the synthesis of comꢀ
pounds 2c,d,g.
3ꢀ(4ꢀBromophenylamino)ꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]chromene)ꢀ
4,4´ꢀdione (3c). Yield 0.11 g (26.5%), white crystals, m.p. 234—
1
235 °C. H NMR (DMSOꢀd6), δ: 6.72 (d, 2 H, H(3″), H(5″),
J3 ,2 = 8 Hz); 7.22 (d, 2 H, H(2″), H(6″), J2 ,3 = 8 Hz);
″
″
″ ″
7.45—7.62 (m, 4 H, H(6), H(8), H(6´), H(8´)); 7.63—7.67 (m,
2 H, H(7), H(7´)); 8.00 (d, 2 H, H(5), H(5´), J5,6 = 8 Hz);
8.06 (s, 1 H, CH); 8.45 (s, 1 H, NH). MS, m/z (Irel (%)): 542
[81Br M +1]+• (100), 540 [79Br M + 1]+• (95). Found (%):
C, 62.15; H, 5.32; N, 2.50. C28H14BrNO6. Calculated (%):
C, 62.24; H, 2.61; N, 2.59.
3ꢀ(4ꢀToluidino)ꢀ2,3´ꢀbi(4Hꢀfuro[3,2ꢀc]chromene)ꢀ4,4´ꢀdione
(3d). Yield 0.07 g (18.6%), yellow crystals, m.p. 248—249 °C.
1H NMR (DMSOꢀd6), δ: 2.12 (s, 3 H, Me); 6.67 (d, 2 H, H(3″),
6. V. F. Traven, I. V. Ivanov, A. S. Pavlov, A. V. Manaev, I. V.
Voevodina, V. A. Barachevskii, Mendeleev Commun., 2007,
17, 345.
7. M. Trkovnik, N. Zivkovic, M. Kules, R. Djudjic, Org. Prep.
Proced. Int., 1978, 10, 215.

1914
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
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8. V. F. Traven, D. V. Kravtchenko, T. A. Chibisova, Mendeleev
Commun., 1997, 7, 249.
12. G. M. Sheldrick, SHELXLꢀ97, University of Göttingen,
Göttingen, Germany, 1997.
9. A. V. Manaev, T. A. Chibisova, K. A. Lyssenko, M. Yu. Antipin,
V. F. Traven, Izv. Akad. Nauk, Ser. Khim., 2006, 2012 [Russ.
Chem. Bull., Int. Ed., 2006, 55, 2091].
13. APEX2 Software Package, Bruker AXS Inc., 5465, East Cheryl
Parkway, Madison, Wisconsin, USA, 2005.
10. A. Bondi, J. Phys. Chem., 1964, 68, 441.
11. G. M. Sheldrick, SHELXSꢀ97, University of Göttingen,
Göttingen, Germany, 1997.
Received December 15, 2008;
in revised form July 17, 2009