Mendeleev Commun., 2011, 21, 231–233
Table 2 Total (E) and relative (DE) energies, total (EZPE) and relative (DEZPE) energies with zero-point energy correction, total (Esolv) and relative (DEsolv
energies in solutions calculated by the B3LYP/6-311++G(d,p).
)
Structure
E (a.u.)
DE/kJ mol–1
EZPE (a.u.)
DEZPE /kJ mol–1
Esolv (a.u.)
DEsolv /kJ mol–1
1 + NH3
2b
2b + H2O
3ha
NH3
H2O
–725.81259
–649.34369
–725.80222
–725.85510
–56.58272
–76.45853
0.0
—
27.2
–111.8
—
–725.57326
–649.12616
–725.56341
–725.60958
–56.54845
–76.43725
0.0
—
26.0
–95.5
—
–725.84395
–649.36817
–725.83789
–725.88130
–56.59005
–76.46972
0.0
—
15.9
–98.0
—
—
—
—
a Characteristics of the energetically most stable conformer 3h are given.
In order to verify this suggestion we independently synthesized
compound 2a from 1H-indole-3-carboxaldehyde 5 via Schiff base
6.¶ However, boiling of starting material 2a in wet propan-2-ol
did not lead to b-aminoalcohol 3a, whereas only resinification
took place. This experiment rules out thermodynamic control and
shows that oxirane ring opening is a quicker process.
To explain experimental facts and compare the stability of
reaction products 2b or 3h obtained by two alternative pathways,
quantum chemical calculations for model reaction of compound
1 with ammonia (R = H) were carried out. Table 2 indicates that
the total energy of system 2b + H2O is higher than the starting
reaction point energy. The energy difference between them is
15.9 kJ mol–1 with taking into account solvation. This result
demonstrates endothermic character of the attack of aldehyde group
of compound 1 by ammonia molecule. At the same time the
addition of ammonia to oxirane ring leading to compound 3h
looks more preferable than system 1 + ammonia by more than
90 kJ mol–1.
Taking into consideration the ability of amines to form asso-
ciates,6 we calculated another potential supramolecular mechanism
of reaction with ammonia dimer (Scheme 2). Two competitive
processes start with the formation of pre-reaction complexes 1'
‡
General procedure for the synthesis of 1-[3-(arylamino)-2-hydroxypropyl]-
CH2, CH), 6.57 (d, 2H, HAr, J 9.2 Hz), 6.75 (d, 2H, HAr, J 8.9 Hz), 6.89
(d, 2H, HAr, J 8.8 Hz), 7.16 (d, 2H, HAr, J 8.9 Hz), 7.25–7.38 (m, 3H,
1H-indole-3-carboxaldehydes 3a–f. To compound 1 (0.2 g, 1 mmol) in
propan-2-ol (3 ml), an aniline (2 mmol) was added and the mixture was
refluxed for appropriate time (see Table 1). In case of 3a,c–f, the formed
precipitate was filtered off and recrystallised. In case of 3b,g, the solvent
was evaporated, benzene (2 ml) was added to the obtained oil (and heated
in case of 3g), the formed precipitate was filtered off and recrystallized
with benzene.
HInd-5,6,7), 7.63 (s, 1H, HInd-2), 8.39–8.49 (m, 1H, HInd-4), 8.59 (s, 1H,
CH=). 13C NMR (CDCl3) d: 49.0, 51.0, 55.9, 56.2, 69.4, 110.2, 114.8 (2C),
115.2, 115.3 (2C), 115.4 (2C), 116.9, 122.1, 122.2 (2C), 122.3, 123.8, 126.7,
134.1, 137.7, 142.3, 146.5, 153.2, 157.9. IR (n/cm–1): 3356, 3179 (OH,
NH), 1609 (C=N), 1590, 1572 (C–CAr). Found (%): C, 72.42; H, 6.31;
N, 9.74. Calc. for C26H27N3O3 (%): C, 72.71; H, 6.34; N, 9.78.
For 3a: yield 50%, mp 159–161°C (propan-2-ol). 1H NMR (CDCl3) d:
1.35–2.21 (bp, 2H, NH, OH), 3.03–3.16 (m, 1H, NCH2), 3.24–3.35 (m,
1H, NCH2), 3.73 (s, 3H, OMe), 4.17–4.50 (m, 3H, CH, CH2), 6.57–6.66
(m, 2H, HAr), 6.72–6.82 (m, 2H, HAr), 7.27–7.41 (m, 3H, HInd-5,6,7), 7.80
(s, 1H, HInd-2), 8.22–8.32 (m, 1H, HInd-4), 9.87 (s, 1H, CH=O). 13C NMR
(CDCl3) d: 49.1, 51.2, 56.2, 69.3, 110.4, 114.7, 115.4, 115.5, 118.7,
122.2, 122.7, 123.5, 124.6, 125.7, 137.9, 140.2, 142.1, 153.4, 185.1. IR
(n/cm–1): 3337, 3369 (OH, NH), 1645 (C=O), 1614, 1576 (C–CAr). Found
(%): C, 70.07; H, 6.19; N, 8.61. Calc. for C19H20N2O3 (%): C, 70.35; H,
6.21; N, 8.64.
For 4b: the solvent was evaporated; diethyl ether (2 ml) and light petro-
leum (3 ml) were added to the obtained oil. The formed precipitate was
filtered off and recrystallized from benzene. Yield 23%, mp 105–107°C.
1H NMR (CDCl3) d: 2.22 (s, 3H, Me), 2.35 (s, 3H, Me), 2.50–2.71 (m, 1H,
NH), 3.02–3.15 (m, 1H, NCH2), 3.22–3.33 (m, 1H, NCH2), 3.64–3.90 (m,
1H, OH), 4.15–4.39 (m, 3H, CH, CH2), 6.49–6.57 (m, 2H, HAr), 6.93–7.02
(m, 2H, HAr), 7.06–7.20 (m, 4H, HAr), 7.25–7.38 (m, 3H, HInd-5,6,7), 7.64
(s, 1H, HInd-2), 8.41–8.49 (m, 1H, HInd-4), 8.59 (s, 1H, CH=). 13C NMR
(CDCl3) d: 20.8, 21.4, 48.3, 51.0, 69.3, 110.3, 114.1 (2C), 115.2, 115.8,
121.1, 122.1, 123.7, 126.8, 128.0, 130.1 (2C), 130.3 (2C), 134.4, 135.1,
137.7, 145.9, 150.8, 154.2. IR (n/cm–1): 3367, 3178 (NH, OH), 1612 (C=N),
1587, 1571 (C–CAr). Found (%): C, 78.87; H, 6.88; N, 10. 61. Calc. for
C26H27N3O (%): C, 78.56; H, 6.85; N, 10. 57. MS, m/z (%): 397 (4.9 [M+]).
For 4c: the formed precipitate was filtered off and recrystallized from
benzene.Yield 43%, mp 136–138°C. 1H NMR (CDCl3) d: 0.70–1.95 [m,
22H, NH, OH, (CH2)10], 2.14–2.34 [m, 1H, NH(CH)cyclohexyl], 2.35–2.53 (m,
1H, NCH2), 2.62–2.82 (m, 1H, NCH2), 2.94–3.21 [m, 1H, =N(CH)cyclohexyl],
3.74–3.99 (m, 1H, CH), 4.00–4.27 (m, 2H, CH2), 7.01–7.40 (m, 3H,
1
For 3b: yield 26%, mp 138–140°C (benzene). H NMR (CDCl3) d:
2.74–2.97 (m, 1H, NH), 3.10–3.24 (m, 1H, NCH2), 3.28–3.42 (m, 1H,
NCH2), 3.81–4.09 (bp, 1H, OH), 4.12–4.49 (m, 3H, CH, CH2), 6.60–6.82
(m, 3H, HAr), 7.08–7.45 (m, 5H, HAr), 7.78 (s, 1H, HInd-2), 8.20–8.31 (m,
1H, HInd-4), 9.77 (s, 1H, CH=O). 13C NMR (CDCl3) d: 48.1, 51.3, 69.1,
110.6, 114.0, 118.5, 118.9, 120.0, 122.5, 123.5, 124.5, 125.6, 129.8, 130.1,
137.9, 140.6, 148.1, 185.3. IR (n/cm–1): 3363 (OH, NH), 1651 (C=O), 1632,
1602 (C–CAr). Found (%): C, 73.74; H, 6.18; N, 9.56. Calc. for C18H18N2O2
(%): C, 73.45; H, 6.16; N, 9.52.
H
Ind-5,6,7), 7.47 (s, 1H, HInd-2), 8.19–8.36 (m, 1H, HInd-4), 8.48 (s, 1H,
CH=). 13C NMR (CDCl3) d: 25.3 (4C), 26.3, 33.9, 35.3 (4C), 49.8, 51.0,
57.1, 69.0, 70.6, 110.0, 115.0, 121.3, 122.2, 123.1, 126.7, 132.2, 137.7,
152.6. IR (n/cm–1): 3056 (NH, OH), 1637 (C=N), 1574, 1536 (C–CAr).
Found (%): C, 75.25; H, 9.21; N, 10.97. Calc. for C24H35N3O (%): C, 75.55;
H, 9.25; N, 11.01. MS, m/z (%): 381 (14.8 [M+]).
For 3c: yield 65%, mp 160–162°C (propan-2-ol–acetonitrile, 4:1).
1H NMR (CDCl3) d: 2.99–3.28 (m, 2H, NCH2), 3.74 (s, 3H, OMe), 4.02–
4.39 (m, 3H, CH, CH2), 4.42–4.67 (bp, 1H, NH), 4.67–4.84 (bp, 1H, OH),
6.33-6.81 (m, 4H, HAr), 7.10–7.37 (m, 3H, HInd-5,6,7), 7.78 (s, 1H, HInd-2),
8.09–8.25 (m, 1H, HInd-4), 9.83 (s, 1H, CH=O). 13C NMR (CDCl3) d:
47.8, 51.3, 55.8, 68.9, 110.1, 110.6, 110.7, 117.7, 118.5, 121.7, 122.5,
123.3, 124.4, 125.7, 138.0, 138.2, 140.7, 147.6, 185.2. IR (n/cm–1): 3330,
3408 (OH, NH), 1632 (C=O), 1614, 1600 (C–CAr). Found (%): C, 70.63;
H, 6.23; N, 8.67. Calc. for C19H20N2O3 (%): C, 70.35; H, 6.21; N, 8.64.
For characteristics of compounds 3d–g, see Online Supplementary
Materials.
¶
Synthesis of 1-(oxiran-2-ylmethyl)-3-[(4-methoxyphenylimino)methyl]-
1H-indole 2a: compound 6 (2.5 g, 10 mmol) in DMSO (7 ml) was added
to sodium hydride (0.5 g of 60% suspension in mineral oil, 12.5 mmol)
for 20 min. The reaction mixture was stirred for 1 h at room temperature.
Then epibromohydrin (2.5 ml, 30 mmol) was added to a cooled solution.
The reaction mixture was stirred for 30 min at room temperature and then
quenched with water (5 ml). The formed precipitate was filtered off and
recrystallized from benzene. Yield 59%, mp 94–96°C. 1H NMR (CDCl3)
d: 2.42–2.48 (dd, 1H, OCH2, J 4.6 and 2.5 Hz), 2.77–2.84 (dd, 1H, OCH2,
J 4.6 and 3.9 Hz), 3.24–3.34 (m, 1H, CH), 3.82 (s, 1H, OMe), 4.09–4.21
(dd, 1H, NCH2, J 15.3 and 5.4 Hz), 4.41–4.52 (dd, 1H, NCH2, J 15.3
and 2.8 Hz), 6.85–7.46 (m, 7H, HInd-5,6,7, 4HAr), 7.55 (s, 1H, HInd-2),
8.42–8.57 (m, 1H, HInd-4), 8.63 (s, 1H, CH=). IR (n/cm–1): 1619 (C=N),
1593, 1572, 1539 (C–CAr). Found (%): C 74.19; H, 5.90; N, 9.10. Calc.
for C19H18N2O2 (%): C, 74.49; H, 5.92; N, 9.14.
§
General procedure for the synthesis of bis-adducts 4a–c. To compound
1 (0.2 g, 1 mmol) in propan-2-ol (3 ml), an amine (2 mmol) was added
and the mixture was refluxed for appropriate time (see Table 1).
For 4a: the solvent was evaporated; diethyl ether (2–3 ml) was added to
the obtained oil. The precipitate was filtered off and recrystallized from
benzene. Yield 30%, mp 106–108°C. 1H NMR (CDCl3) d: 1.44–1.84 (bp,
1H, NH), 2.65–2.92 (bp, 1H, OH), 2.99–3.14 (m, 1H, NCH2), 3.18–3.30
(m, 1H, NCH2), 3.73 (s, 1H, OMe), 3.81 (s, 1H, OMe), 4.13–4.41 (m, 3H,
– 232 –