214 JOURNAL OF CHEMICAL RESEARCH 2015
condensation with diethylmalonate followed by hydrolysis
and decarboxylation,7 the procedure has proven tedious and
cumbersome. Fortunately, in our case, 4-(diethylamino)
salicylaldehyde (3) can be subjected to the Wittig reaction
In summary, the concise synthesis of 3-(2-benzimidazolyl)-
7-(diethylamino)coumarin known as coumarin-7 and its isomer
4-(2-benzimidazolyl)-7-(diethylamino)coumarin using the
formylcoumarin as vital intermediate has been described. The
bridging position between the benzimidazole and coumarin
moiety was found to have a significant effect on the UV-Vis
absorption and fluorescence emission properties of these
coumarins. Further work is in progress in our laboratory.
with
(ethoxycarbonylmethylene)triphenylphosphorane
in
ethanol to afford 7-(diethylamino)coumarin (4) in 76% yield.
Subsequently, the coumarin 4 underwent the Vilsmeier-Haack
reaction with DMF and POCl3 to provide the vital intermediate
3-formylcoumarin 5 in 82% yield. Finally, compound 5
was smoothly condensed with o-phenylenediamine in the
presence of sodium bisulfite in methanol to afford the
3-(2-benzimidazolyl)-7-(diethylamino)coumarin (1) in 75%
yield. We also examined the same condensation in methanol
without sodium bisulfite, whereby the desired product 1 was
obtained in unsatisfactory yield along with many byproducts.
The synthesis of 4-(2-benzimidazolyl)-7-(diethylamino)
coumarin (2) was achieved by using m-diethylaminophenol
(6) as starting material, which was subjected to the Pechmann
reaction with ethyl acetoacetate catalysed by ZnCl2 under
solvent-free conditions to afford the 4-methylcoumarin 7 in
78% yield. Compound 7 was then oxidised by SeO2 in xylene
to give the 4-formylcoumarin 8 in 63% yield. Eventually, the
intermediate 8 was transformed to 4-(2-benzimidazolyl)-7-
(diethylamino)coumarin (2) in 72% yield also by reacting with
o-phenylenediamine in methanol promoted by sodium bisulfite.
Because the synthesised coumarins 1 and 2 possess similar
structures but have different linking positions between the
benzimidazole and coumarin moieties, we were especially
interested to investigate their fluorescent properties for comparison
with each other. The UV–Vis absorption spectra of 1 and 2 in diluted
dichloromethane solutions are presented in Fig. 1. It is shown that
the absorption maxima of 1 locates at 437 nm, which is identical
with that observed in chloroform solution.8 The absorption spectrum
of 2 exhibits two peaks at 322 and 419 nm, respectively. Compared
with 1, the absorption maxima of 2 (419 nm) is clearly blue-shifted,
suggesting that coumarin-7 1 exhibits larger conjugation than the
isomer 2. Figure 1 also shows the fluorescence spectra of 1 (excited
at 437 nm) and 2 (excited at 419 nm) in diluted dichloromethane
solutions. It is shown that the coumarin-7 1 exhibits the emission
peak at 486 nm, which is identical with the reported value in acetone
solution.8 The emission maxima of 2 is found to locate at 518 nm,
obviously red-shifted by about 32 nm compared with that of 1. As
a result, the Stoke’s shift of 2 is larger than that of 1, indicating
that the change in geometry between the ground state and the first
excited singlet state of 2 is larger than that of 1.9
Experimental
Reagents and solvents were all from commercial sources and used
without further purification. IR spectra were performed on a Digilab
FTS-3000 FT-IR spectrophotometer. 1H NMR and 13C NMR spectra
were recorded on a Mercury Plus 400 MHz spectrometer. Melting
points were measured on a Kofler apparatus and uncorrected.
Column chromatography purifications were performed on 200–300
mesh silica gel. Analytical TLC was performed on silica gel GF254
plates. High resolution mass spectra (HRMS) were determined on
a Bruker Daltonics APEX II 47e spectrometer. UV-Vis absorption
and fluorescence spectra were recorded on a Hitachi U-3900H
spectrometer and on an Edinburgh instruments FLS920 spectrometer,
respectively.
7-(Diethylamino)coumarin (4): 4-(Diethylamino)salicylaldehyde
(0.39 g, 2.0 mmol) and (ethoxycarbonylmethylene)triphenylphosphorane
(1.04g, 3.0 mmol) was dissolved in ethanol (20 mL). The resulting
solution was stirred under reflux conditions for 6 h. On completion of
the reaction (monitored by TLC), the ethanol was evaporated under
reduced pressure. The resulting residue was purified by column
chromatography using petroleum ether/ethyl acetate (v/v = 5:1) as
eluent to afford 4 in 76% yield as yellow solid, m.p. 87–88 °C (lit.10
1
88–89 °C). H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 9.2 Hz, 1H),
7.23 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.44 (s, 1H), 6.00
(d, J = 9.2 Hz, 1H), 3.38 (q, J = 6.8 Hz, 4H), 1.19 (t, J = 6.8 Hz, 6H).
13C NMR (100 MHz, CDCl3): δ 162.1, 156.6, 150.5, 143.7, 128.8, 108.8,
108.6, 108.1, 97.2, 44.6, 12.3.
7-Diethylamino-3-formylcoumarin (5):7 Freshly distilled DMF
(1 mL) was added dropwise to POCl3 (1 mL) at room tempreture and
stirred for 30 min to yield a red solution. This solution was combined
with another solution of 7-(diethylamino)coumarin (0.33 g, 1.5
mmol) in DMF (2 mL) and the resulting mixture was stirred at 60
°C for 7 hours. When the reaction was judged to be complete (TLC
monitoring), the mixture was poured into 30 mL of ice water. NaOH
solution (20%) was added to adjust the pH of the mixture to yield
large amount of precipitate. The crude product was filtered, washed
thoroughly with water, dried and recrystallised in ethanol to give 5
1
as yellow solid in 82% yield, m.p. 166–167 °C. H NMR (400 MHz,
CDCl3): δ 10.10 (s, 1H), 8.22 (s, 1H), 7.40 (d, J = 8.8 Hz, 1H), 6.64
(dd, J = 8.8 and 2.0 Hz, 1H), 6.48 (s, 1H), 3.48 (q, J = 7.2 Hz, 4H), 1.26
(t, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 187.9, 161.9, 159.0,
153.6, 145.5, 132.6, 114.3, 110.4, 108.3, 97.2, 45.4, 12.6.
1
2
1.0
7-Diethylamino-4-methylcoumarin (7):
A
mixture of ethyl
acetoacetate (0.39 g, 3.0 mmol), m-diethylaminophenol (0.50 g, 3.0
mmol) and ZnCl2 (0.40 g, 3.0 mmol) in a mortar was ground well with a
pestle at room temperature. Then, the mixture was heated at 50 °C and
ground for 30 min. The resulting solid was dissolved in ethyl acetate
(50 mL), extracted with brine (3×50 mL). The organic layer was
dried over Na2SO4, filtered and concentrated under reduced pressure.
The resulting residue was purified by column chromatography using
petroleum ether/ethyl acetate (v/v = 5:1) as eluent to afford 7 in 78%
yield as colourless solid, m.p. 72–74 °C (lit.11 72–75 °C). 1H NMR (400
MHz, CDCl3): δ 7.36 (d, J = 8.8 Hz, 1H), 6.57 (d, J = 8.8 Hz, 1H), 6.48
(s, 1H), 5.92 (s, 1H), 3.39 (q, J = 7.2 Hz, 4H), 2.32 (s, 3H), 1.19 (t, J =
7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 162.1, 156.0, 152.8, 150.4,
125.5, 109.0, 108.7, 108.4, 97.6, 44.7, 18.4, 12.4.
0.5
0.0
300
400
500
600
Wavelength/nm
7-Diethylamino-4-formylcoumarin (8): 7-Diethylamino-4-methyl-
coumarin (0.46 g, 2.0 mmol) and SeO2 (0.34 g, 3.0 mmol) were
dissolved in xylene (10 mL). The resulting solution was stirred
Fig. 1 Normalised absorption and emission spectra of coumarin-7 1 and
its isomer 2 in dichloromethane (1 × 10–5 mol L–1).