Mendeleev Commun., 2012, 22, 314–316
of the NH and OH functions (11.81–12.16 and 8.68–9.45 ppm,
of the amino group with the dienone system up to the transfer of
lone electron pair on the carbonyl oxygen. Owing to this, the
free rotation around the loosen double bond becomes possible
(Scheme 5). Significant decrease of the rotation barrier around the
polarized double bond (up to 60–90 kJ mol–1) has been observed
for many push-pull ethylenes.11
respectively) are detectable. The values of chemical shifts of
hydrogen and nitrogen atoms in the amino acid counterpart of
compounds 5a–c are in good agreement with the spectral data
of g-aminobutanoic acid obtained under the conditions excluding
the formation of zwitterionic forms.10
Compounds 5a–c on heating in ethanol (78°C, 4 h) underwent
dehydrocyclization to give 3-acyl-2,6-diphenylpyridines 6a–c
(82–89% yields)‡ and g-butyrolactone 7 (Scheme 3). Their struc-
ture was established (1H NMR) by the characteristic pyridine
doublets at 7.80–7.89 and 7.96–8.03 ppm (3J 7.4–8.1 Hz) and
the CH2-proton signals at 2.28, 2.48 and 4.35 ppm of g-butyro-
lactone 7.
In the primary adducts 1 the C–N bond cleavage in the
g-aminobutyric moiety did not take place even on prolonged
(15 h) refluxing in EtOH. It follows unambiguously that for
such bond cleavage, the presence of aminodienone system in
the molecules is required.
Ph
Ph
O
O
O
Ph
NH
Ph
NH
E
Z
EtOH, 78 °C, 4 h
– H2O
R
R
R
+
5a–c
O
O
O
O
Ph
N
Ph
HO2C
HO2C
Ph
a R = Ph
b R = 2-furyl
6a–c
7
(1Z,3E)-5a–c
c R = 2-thienyl
R
O
Scheme 3
E
NH
O
Z
Noteworthy, the pyridine formation is accompanied by the
unexpected cleavage of the C–N bond, unusual for GABA and
generally for alkylamines. Apparently, the both processes are
interrelated and proceed as outlined in Scheme 4. The dienone
carbonyl group is intramolecularly attacked by the amino group
to close dihydropyridine cycle A, which further is aromatized to
acylpyridines via the elimination of 4-hydroxybutyric acid B (giving
finally g-butyrolactone 7).
HO2C
Ph
(1E,3Z)-5a–c
Scheme 5
In conclusion, a facile and convenient approach to novel poly-
functional derivatives of GABA, representing a synthetic hybrid
of pharmacophoric fragments of the amino acid, enaminones and
chalcones,12 has been developed. The compounds synthesized can
also be considered as merocyanine analogues, ‘donor–acceptor-
substituted polyenes’, which find applications in the design of
new optoelectronic materials, information carriers, electrolumi-
nescent devices as well as probes and markers for chemical
analysis, biology and medicine.13
R
HO2C
Ph
N
O
+
5a–c
6a–c
HO2C
OH
B
7
HO
Ph
– H2O
A
‡
Scheme 4
Synthesis of 3-acyl-2,6-diphenylpyridines 6a–c. Compound 5a–c
(0.5 mmol) was dissolved in EtOH (10 ml) and stirred at 78°C for 4 h.
The solvent was half-evaporated, the concentrate was kept at ~0°C for
one day, the crystals precipitated were filtered off and dried in vacuo.
3-Benzoyl-2,6-diphenylpyridine 6a: yield 83%, colourless crystals,
mp 102–104°C. IR (n/cm–1): 1664 (C=O), 1569–1595 (C=C, C=N).
1H NMR, d: 7.86 (d, 1H, H5pyr, 3JHH 7.4 Hz), 7.96 (d, 1H, H4pyr, 3JHH 7.4 Hz),
7.26–7.72, 8.22 (m, 15H, Ar). 13C NMR, d: 117.9, 127.3, 128.3, 128.4,
128.9, 129.5, 129.8, 129.9, 132.6, 133.3, 136.9, 138.3, 138.5, 139.6, 157.3,
158.1, 197.6. 15N NMR, d: –72.5. Found (%): C, 85.63; H, 5.43; N, 4.02.
Calc. for C24H17NO (%): C, 85.94; H, 5.11; N, 4.18.
For such a cyclization it is necessary that adduct 5, initially
of the Z,E-configuration, would accept the E,Z-configuration. This
E/Z-isomerization is facilitated by the deep push-pull conjugation
4-{[(1Z,3E)-2-(2-Furylcarbonyl)-5-oxo-1,5-diphenylpenta-1,3-dienyl]-
amino}butanoic acid 5b: yield 83%, yellow crystals, mp 38–40°C. IR
(n/cm–1): 3127–2927 (NH, OH), 1728 (COOH), 1646 (C=O), 1597 (C=O).
1H NMR, d: 1.85 (m, 2H, CH2), 2.34 (m, 2H, CH2), 3.14 (m, 2H, CH2),
5.83 (d, 1H, O=C–CH=, 3JHH 15.4 Hz), 6.48 (dd, 1H, Hf4ur, 3JHH 3.4 Hz,
3
4
3JHH 1.5 Hz), 7.01 (dd, 1H, H3fur, JHH 3.4 Hz, JHH 0.8 Hz), 7.35–7.84
(m, 12H, Ar, H5fur, =C–CH=), 9.20 (br.s, 1H, OH), 12.16 (br.s, 1H, NH).
13C NMR, d: 25.2, 30.8, 44.2, 111.7, 117.1, 117.5, 127.8, 128.0, 129.4,
129.9, 131.6, 133.0, 138.7, 143.9, 145.0, 152.7, 168.9, 176.5, 181.5, 189.3.
15N NMR, d: –252.3. Found (%): C, 72.87; H, 5.44; N, 3.22. Calc. for
C26H23NO5 (%): C, 72.71; H, 5.40; N, 3.26.
3-(2-Furylcarbonyl)-2,6-diphenylpyridine 6b: yield 89%, yellow wax-
like solid, mp 38–40°C. IR (n/cm–1): 1648 (C=O), 1549–1582 (C=C,
C=N). 1H NMR, d: 6.33 (dd, 1H, H4fur), 6.85 (dd, 1H, H3fur), 7.80 (d, 1H,
3
3
H5pyr, JHH 8.1 Hz), 7.96 (d, 1H, H4pyr, JHH 8.1 Hz), 7.26–7.67, 8.16 (m,
11H, Ar, H5fur). 13C NMR, d: 112.4, 117.9, 120.5, 127.4, 128.4, 128.9,
129.3, 129.8, 131.7, 138.3, 138.4, 139.8, 147.3, 152.3, 157.3, 158.3, 184.5.
15N NMR, d: –71.8. Found (%): C, 81.44; H, 4.62; N, 4.13. Calc. for
C22H15NO2 (%): C, 81.21; H, 4.65; N, 4.30.
4-{[(1Z,3E)-5-Oxo-1,5-diphenyl-2-(2-thienylcarbonyl)penta-1,3-dienyl]-
amino}butanoic acid 5c: yield 90%, yellow crystals, mp 42–44°C. IR
(n/cm–1): 3266–2930 (NH, OH), 1728 (COOH), 1647 (C=O), 1593 (C=O).
1H NMR, d: 1.79 (m, 2H, CH2), 2.27 (m, 2H, CH2), 3.09 (m, 2H, CH2),
3-(2-Thienylcarbonyl)-2,6-diphenylpyridine 6c: yield 82%, colourless
crystals, mp 128–130°C. IR (n/cm–1): 1646 (C=O), 1552–1584 (C=C,
C=N). 1H NMR, d: 6.98 (dd, 1H, H4thienyl), 7.89 (d, 1H, H5pyr, 3JHH 8.1 Hz),
3
5.90 (d, 1H, O=C–CH=, JHH 15.5 Hz), 7.02–7.78 (m, 14H, Ar, HetAr,
3
=C–CH=), 8.68 (br. s, 1H, OH), 11.81 (br. s, 1H, NH). 13C NMR, d:
25.4, 31.2, 44.4, 105.0, 117.1, 127.7, 128.0, 128.1, 129.5, 129.8, 130.1,
131.3, 131.8, 132.1, 133.2, 138.9, 145.0, 145.5, 168.6, 177.0, 187.0, 189.3.
Found (%): C, 71.26; H, 5.44; N, 3.22; S, 7.61. Calc. for C26H23NO4S
(%): C, 70.09; H, 5.20; N, 3.14; S, 7.20.
8.03 (d, 1H, H4pyr, JHH 8.1 Hz), 7.34–7.79, 8.26 (m, 12H, Ar, H3thienyl
,
H5thienyl). 13C NMR, d: 117.8, 127.3, 128.2, 128.4, 128.9, 129.0, 129.4,
129.8, 132.6, 135.1, 135.3, 137.9, 138.4, 139.6, 144.2, 156.8, 158.2, 189.5.
15N NMR, d: –66.6. Found (%): C, 77.49; H, 4.78; N, 4.38; S, 9.08. Calc.
for C22H15NOS (%): C, 77.39; H, 4.43; N, 4.10; S, 9.39.
– 315 –