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Z. Soyer et al. / IL FARMACO 59 (2003) 595–600
Table 4
NMR data of title compounds 2–9
Comp.
2
NMR
1
H NMR (CDCl ): 1.03 (d, 6H, J= 6.8, 2xCH ), 2.48-2.51 (m, 1H, CH), 4.78 (s, 2H, CH ), 6.95 (brs, N-H), 7.01 (s, 1H, H-5’), 7.11-7.19 (m, 4H,
3
3
2
H-3, H-4, H-5, H-4’), 7.57 (s, 1H, H-2’), 7.68 (d, 1H, J= 7.1, H-6)
1
3
C NMR (CDCl ): 23.2, 28.4, 50.9, 120.1, 124.9, 126.1, 126.8, 127.1, 131.2, 133.4, 138.5, 141.1, 165.8
3
1
3
4
5
H NMR (DMSO-d ): 1.06 (d, 6H, J= 6.8, 2xCH ), 2.81 (t, 2H, J=6.6, a-H), 2.90-3.01 (m, 1H, CH), 4.26 (t, 2H, J=6.6, b-H), 6.87 (s, 1H, H-5’),
6
3
7
.12-7.18 (m, 4H, H-3, H-4, H-5, H-4’), 7.28 (d, 1H, J=7.5, H-6), 7.59 (s, 1H, H-2’), 9.39 (brs, N-H)
1
3
C NMR (CDCl ): 23.7, 28.3, 38.8, 43.4, 119.8, 126.3, 126.5, 126.7, 127.3, 128.7, 129.6, 133.9, 137.5, 142.8, 169.1
3
1
H NMR (DMSO-d ): 2.12 (s, 6H, 2xCH ), 4.90 (s, 2H, CH ), 6.90 (s, 1H, H-5’), 7.04-7.06 (m, 3H, H-3, H-4, H-5), 7.16 (s, 1H, H-4’), 7.64 (s,
6
3
2
1
H, H-2’), 9.57 (brs, N-H)
1
3
C NMR (CDCl ): 18.7, 18.9, 50.4, 120.2, 128.1, 128.7, 129.5, 130.8, 133.1, 135.5, 138.4, 165.8
3
1
H NMR (DMSO-d ): 2.00 (s, 6H, 2xCH ), 2.82 (t, 2H, J=6.6, a-H), 4.27 (t, 2H, J=6.6, b-H), 6.88 (s, 1H, H-5’), 7.01-7.04 (m, 3H, H-3, H-4,
6
3
H-5), 7.16 (s, 1H, H-4’), 7.59 (s, 1H, H-2’), 9.30 (brs, N-H)
1
H NMR (CDCl ): 2.09 (s, 6H, 2xCH , min.), 2.12 (s, 6H, 2xCH ), 2.32 (t, 2H, J=6.3, a-H, min), 2.85 (t, 2H, J=6.3, a-H), 4.27 (t, 2H, J=6.3, b-H,
3
3
3
min), 4.40 (t, 2H, J=6.4, b-H), 6.99-7.11 (m, 6H, H-3, H-4, H-5, H-4’, H-5’and N-H), 7.13-7.15 (m, 1H, min.), 7.44 (s, 1H, min), 7.52 (s, 1H, H-2’)
1
3
C NMR (CDCl ): 18.6, 18.5 (min), 34.3 (min), 37.9, 42.4 (min), 43.4, 119.5 (min), 119.6, 127.8, 128.5, 129 (min), 129.1, 129.6, 129.7 (min),
3
1
34.2, 135.7, 137.1 (min), 137.5, 137.7 (min), 168.5, 172.1 (min)
1
6
7
H NMR (CDCl ): 4.87 (s, 2H, CH ), 7.12 (s, 1H, H-5’*), 7.14 (s, 1H, H-4’*), 7.21 (t, 1H, J=8.1, H-4), 7.38 (d, 2H, J=8.1, H-3, H-4), 7.55 (s, 1H,
3
2
H-2’), 8.36 (brs, N-H)
1
3
C NMR (CDCl ): 50.6, 120.2, 128.9, 129.6, 131.2, 131.5, 134.3, 138.5, 165.6
3
1
H NMR (CDCl +DMSO-d ): 2.85 (t, 2H, J=6.3, a-H), 4.31 (t, 2H, J=6.4, b-H), 6.95 (s, 2H, H-4’, H-5’), 7.10 (t, 1H, J=8.0, H-4), 7.28 (d, 2H,
3
6
J=8.1, H-3, H-5), 7.47 (s, 1H, H-2’), 8.95 (brs, N-H)
1
H NMR (DMSO-d ): 2.86 (t, 2H, J=6.7, a-H), 4.28 (t, 2H, J=6.7, b-H), 6.88 (s, 1H, H-5’), 7.18 (s, 1H, H-4’), 7.35 (t, 1H, J=7.8, H-4), 7.52 (d,
6
2
H, J=8.1, H-3, H-5), 7.62 (s, 1H, H-2’), 9.96 (brs, N-H)
1
1
1
1
3
C NMR (CDCl +DMSO-d ): 32.4, 38.1, 114.6, 123.7, 124.0, 124.4, 128.2, 129.5, 132.6, 164.1
3
6
8
9
H NMR (CDCl ): 2.20 (s, 3H, CH ), 4.84 (s, 2H, CH ), 7.09-7.24 (m, 6H, H-3, H-4, H-5, H-4’, H-5’, N-H), 7.61 (s, 1H, H-2’)
3 3 2
3
C NMR (CDCl ): 19.0, 50.1, 120.5, 122.1, 127.6, 128.8, 129.5, 130.0, 132.2, 132.3, 138.4 166.2
3
H NMR (DMSO-d ): 2.00 (s, 3H, CH ), 2.85 (t, 2H, J=6.6, a-H), 4.28 (t, 2H, J=6.6, b-H), 6.88 (s,1H, H-5’), 7.18-7.22 (m, 3H, H-4, H-5, H-4’),
6
3
7
.33 (dd, 1H, J= 2.9, 6.6, H-3’), 7.62 (s, 1H, H-2’), 9.64 (brs, N-H)
1
3
C NMR (CDCl ): 19.0, 37.6, 43.4, 119.9, 122.1, 124.0, 127.6, 128.5, 129.4, 133.2, 135.4, 138.6, 169.3.
3
*
Interchangeable.
–
1
region, which correspond to the minor signal/major signal
ratio. The highest minor/major ratio was observed in com-
pound 5a (1/4) followed by compounds 3a (1/7), 7a (1/11)
and 9a (1/11), respectively. Those minor signals (not re-
ported) would be due to the two different rotamer formation
1680 cm , respectively, indicating the presence of an anilide
1
structure (Table 3). In acetamide series, H NMR spectra
confirmed the presence of expected proton signals with rel-
evant splitting patterns and integrations. However, in propi-
onamide series, H NMR spectra recorded in CDCl (except
1
3
(
i.e. E/Z rotamers in seconder amides) in CDCl . In order to
compound 7 of which the spectrum recorded in CDCl3–
3
1
clarify the situation, high temperature H NMR spectra were
DMSO-d mixture), displayed additional unexpected minor
6
recorded for compounds 3a, 5a and 7a, since recording low
signals due to two different rotamers, as is the case in propi-
onamide intermediates. The highest minor/major ratio ob-
served for compound 5 (1/3) followed by compounds 3 (1/5)
and 9 (1/8), respectively. Major and detectable minor rotamer
1
important in confirmation of intramoleculer motions [23,24].
For compounds 3a and 7a, the major and minor signals
combined at coalescence temperature (343 and 335 K, re-
spectively) and the signals and integrations matched the
expected ones, confirming the rotamer formation. However,
in compound 5a, some major and minor signals, although
becoming broader, still remained uncombined at the highest
signals in CDCl for compound 5 were summarized at
3
1
Table 4 as an example. High temperature H NMR experi-
ments were run for compound 5 which display the highest
rotamer ratio. By gradually heating up to point permitted by
CDCl , converging methyl signals were combined at 335 K.
3
temperature permitted by CDCl (343 K). This result indi-
cated that the intramoleculer rotation barrier in compound 5a
was higher than those for compounds 3a and 7a.
Concerning the title compounds, they had N–H and C=O
stretching bands in the region of 3486–3112 and 1658–
In this coalescence temperature for methyl signals, triplets of
methylene protons became broader and they were not com-
bined even at 343 K as seen in corresponding intermediate
5a. In NMR experiments, solvent polarity dependent behav-
ior of rotamer mixtures is quite well known [23–25]. So, we
3