MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2006; 44: 1122–1127
Published online 26 September 2006 in Wiley InterScience
Spectral Assignments and Reference Data
with amino substituents on the B ring, with the purpose of verifying
which of them was more adequate in terms of yields and practical
execution (Table 1).
Synthesis and structure elucidation of five
series of aminoflavones using 1D and 2D
NMR spectroscopy
Comparing the two synthetic pathways to obtain aminoflavones
2a–z, one can conclude that: (i) the approach involving ammonium
formate, Pd/C, is generally more favourable, in terms of yields and
practical execution; for these reasons, it was the method applied
to all compounds, and the method using stannous chloride only
applied to the first series of compounds (without substituents on
the A ring); (ii) the diamino derivatives were obtained in lower
yields than the other derivatives (49–58%); (iii) orto-aminoflavones
were obtained in moderate yields (59–69%), with the exception
of 20-amino-6-bromoflavone 2x, which was obtained in 80% of
the yield; all the other derivatives were obtained in similar
yields; meta-aminoflavones 2b, 2e, 2h and 2k (68–79%); para-
aminoflavones 2c, 2f, 2i and 2l (64–76%); 30-amino-20-methylflavones
2m, 2r (64–70%); 30-amino-40-methylflavones 2p, 2n, 2s and 2u
(65–79%).
Ana I. R. N. A. Barros1∗ and Artur M. S. Silva2
1
Chemistry Department, University of Tra´ s-os-Montes e Alto Douro,
5001-801 Vila Real, Portugal
2
Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal
Received 8 June 2006; revised 24 July 2006; accepted 25 July 2006
Twenty-six new aminoflavones have been synthesised
by two different methods and the structure elucidation
was accomplished using extensive 1D (1H, 13C) and 2D
NMR spectroscopic studies (COSY, HSQC and HMBC
experiments). Copyright 2006 John Wiley & Sons, Ltd.
KEYWORDS: NMR; 1H NMR; 13C NMR; HMBC; nitroflavones;
aminoflavones
RESULTS AND DISCUSSION
The full characterisation of compounds 2a–z is presented in
Tables 2–5. The compounds are grouped in five different series.
The 1H NMR spectra of the compounds were well resolved and
the unambiguous proton chemical-shift assignments were based
on the multiplicity pattern of proton resonances and also on the
use of homonuclear 1H–1H COSY spectra. From the NMR spectra
of flavones 2a–z, one can find some typical proton and carbon
resonances, namely, those of H-3 (singlet at υ 6.36–6.86 ppm), C-3 (υ
160.9–167.0 ppm) and C-4 (υ 175.6–178.6 ppm). The C-4 assignment
was based on their high-frequency value, since it is the most
deshielded carbon atom of flavones 2a–z, while that of C-3 was based
on the correlation with H-3 in the HSQC of 2a–z. The assignments
of all carbon resonances of flavones 2a–z were based on the analysis
of the HSQC and HMBC spectra (Fig. 1, shows some of the typical
connectivities found in their HMBC spectra).
INTRODUCTION
During the past decades, there has been a growing interest in the
search for biologically active compounds. Synthesis of flavones and
their derivatives have attracted considerable attention owing to
their significant pharmaceutical,1–4 biocidal5–7 and antioxidant8,9
activities.
Flavones (2-phenylchromones) are one of the most important
classes of natural compounds belonging to the flavonoid family.10
Recently, it has been reported that some synthetic aminoflavones
are potential antineoplastic agents11 and have been proved to be
antimutagenic in the Ames test using different species of mutagens.12
They also exhibit potent cytotoxicity against human breast cancer.13
Taking into account the potential biological applications of
flavones, especially those having amino-substituents, we decided to
devote some attention to the reduction of five series of nitroflavones
once synthesised.14 Compounds 2a–z were prepared by two
different methods: (i) ammonium formate, Pd/C, using methanol
as solvent; (ii) SnCl2.2H2O/HCl, using acetic acid as solvent.
In this paper, we present the synthesis of aminoflavones, and
unambiguous structural elucidation of compounds 2a–z by one-
dimensional (1D) and two-dimensional (2D) NMR experiments.
Taking 2r (30-amino-20-methyl-5-methoxyflavone) (Fig. 2(a)) as
an example, we can identify in 1H NMR spectra, four singlets at
υ 2.21, υ 3.81, υ 4.01 and υ 6.36 ppm, corresponding to CH3, NH2,
OCH3 and H-3, respectively (Fig. 2(b)).
To confirm the assignments made from HSQC and COSY spectra
and to deduce more information about the structure of flavone 2r, a
2D HMBC spectrum was recorded (Fig. 3).
From this spectrum we can conclude that:
(i) the protons from the methoxyl group at υ 4.01 ppm show long-
range correlation with the carbon resonance for C-5 at υ 159.8 ppm;
(ii) the protons from the methyl group at υ 2.21 ppm show long-range
correlations with the carbon resonances for C-30 at υ 145.4 ppm, C-
10 at υ 130.3 ppm and C-20 at υ 120.5 ppm; (iii) H-3 signal at υHꢀ3
6.36 ppm is correlated with the carbon resonances for C-2, C-10 and
C-10, at υ 164.2 ppm, 130.3 ppm and 114.5 ppm, respectively. The
C-10 signal is also correlated with the H-6 and H-8 resonances at
υ 6.84 and 7.04 ppm. Unambiguous conectivities from these signals
EXPERIMENTAL
13
The 1H and C NMR spectra were recorded at 25 C for ¾5-mg
°
samples dissolved in 0.5 ml of CDCl3 or DMSO-d6 in 5-mm NMR
tubes, using a Bruker DRX 300 spectrometer (300.13 for 1H and 75.47
for 13C). Chemical shifts (υ) were reported in ppm and coupling
constants (J) in Hz. The internal standard was TMS. The Fourier
transform NMR measurement conditions were as follows: for 1H
R7
°
NMR, pulse with 3.4 µs, acquisition time 2.7 s, pulse angle 30 and
number of scans 80; for 13C NMR, pulse with 1.7 ms, acquisition
R6
R5
°
time 0.8 s, pulse angle 30 , number of scans 6144 and number of data
H
H
points 16 384. Unequivocal 13C assignments were made with the aid
of 2D gHSQC and gHMBC (delays for one bond and long-range
J C/H couplings were optimised for 147 and 7 Hz, respectively)
experiments.
R1
R2
O
R4
Materials
H
The synthesesforcompounds 1a–zhave beenpublishedelsewhere.14
Once the nitroflavones 1a–z were obtained, the two reduction
methods were applied in the synthesis of new derivatives of flavones,
R3
O
ŁCorrespondence to: Ana I. R. N. A. Barros, Chemistry Department,
University of Tra´s-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal.
E-mail: abarros@utad.pt
2 a-z
Figure 1. Typical connectivities found in the flavones HMBC spectra.
Copyright 2006 John Wiley & Sons, Ltd.
Barros, Ana I. R. N. A.
