Synthesis and oxidation of 2-furyl-4-R-substituted and furo[3,2-c]- condensed 1,2,3,4-tetrahydro-1,10-phenanthrolines and quinolines

Article abstract of DOI:10.1007/s10593-009-0271-1

2-Furyl-4-substituted and furo[2,3-c]-condensed 1,2,3,4-tetrahydro-1,10- phenanthrolines were obtained for the first time from 8-aminoquinolines using the Povarov reaction. Various oxidizing agents were shown to effect the elimination of the substituent a

Full text of DOI:10.1007/s10593-009-0271-1

Chemistry of Heterocyclic Compounds, Vol. 45, No. 3, 2009
SYNTHESIS AND OXIDATION OF 2-FURYL-
4-R-SUBSTITUTED AND FURO[3,2-c]-CONDENSED
1,2,3,4-TETRAHYDRO-1,10-PHENANTHROLINES
AND QUINOLINES*
V. P. Zaitsev1, N. M. Mikhailova1, D. N. Orlova1, E. V. Nikitina1,
E. V. Boltukhina1, and F. I. Zubkov1**
2-Furyl-4-substituted and furo[2,3-c]-condensed 1,2,3,4-tetrahydro-1,10-phenanthrolines were
obtained for the first time from 8-aminoquinolines using the Povarov reaction. Various oxidizing agents
were shown to effect the elimination of the substituent at C(4) with subsequent aromatization of the
tetrahydroquinoline fragment.
Keywords: tetrahydroquinolines, 1,10-phenanthrolines, oxidation, Povarov reaction.
The Povarov reaction (the acid-catalyzed [4+2] cycloaddition of electron-rich alkenes to
N-arylazomethines) is commonly used for the synthesis of substituted tetrahydroquinolines and, judging from
the rising number of publications, is now experiencing a rebirth of interest [1-3]. Nevertheless, there have been
only a few examples of the preparation of 2-furyl-1,2,3,4-tetrahydroquinolines by this method [4-6] and there is
only one example of the use of an 8-aminoquinoline in the Povarov reaction [7]. This paucity is related primarily
to the acidophobic nature of the furan fragment and, secondarily, to passivation of the acid catalysts. The
behavior of 2-furyltetrahydroquinolines in the presence of oxidizing agents has also not been studied extensively
and apparently is complex.
2-Furyltetrahydroquinolines 2a,b, 3, and 4 used as the starting compounds in this work were obtained
by the Povarov reaction from the corresponding furfurylideneanilines 1a,b and electron-rich alkenes
(dihydrofuran, 3,4-2H-dihydropyran, and N-vinyl-2-pyrrolidone) in the presence of boron trifluoride etherate as
described in our previous work [8]. The hydrogenated quinolines 2-4 are cis addition adducts.
_______
* Dedicated to Professor Aleksei V. Varlamov of the Russian Peoples Friendship University on the occasion of
his seventieth jubilee.
** To whom correspondence should be addressed, e-mail: fzubkov@sci.pfu.edu.ru.
1Russian Peoples Friendship University, Moscow 117198, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 383-392, March, 2009. Original
article submitted March 2, 2009.
308
0009-3122/09/4503-0308©2009 Springer Science+Business Media, Inc.

By analogy, azomethines 5a-c, obtained by the condensation of furfural with α-naphthylamine and also
with 8-amino-6-chloro- and 8-amino-6-bromoquinolines, are converted by cyclocondensation with
2,3-dihydrofuran into 1:1.1-1.5 mixtures of geometric isomers of furo[3,2-c]condensed hexahydro-
1,10-phenanthrolines or the corresponding benzoquinolines 6a-c.
R
R
OHC
O
O
PhH, 80°C
O
N
NH2
1 a,b
( )n
O
N
BF3·OEt2
BF3·OEt2
( )n
O
R
O
N
O
N
H
O
N
H
2 a,b, 3 (23–58%)
4 (80 %)
1a, 2a, 3, 4 R = H; 1b, 2b R = F; 2a, b n = 1; 3 n = 2
Only cis diastereomers 6d,e are obtained in low yield in the reaction of aldimines 5a,c (see
Experimental). The predominant cis isomers of adducts 6a-c were isolated as pure products by fractional
recrystallization.
NH2
X
O
OHC
+
O
R
HN
X
O
PhMe
O
6 a–c
(21–48%)
O
BF3·OEt2
R
N
O
X
O
N
R
HN
O
6 d,e
(11%)
5 a–c
X
N
BF3·OEt2
R
5a, 6a, d X = N, R = Cl; 5b, 6b X = N, R = Br; 5c, 6c, e X = CH, R = H
309

TABLE 1. Physicochemical Characteristics of Compounds 6-10 and 13
Found, %
——————
Calculated, %
IR spectrum,
Com-
pound
Empirical
formula
mp, ºС
Rf*
ν, cm-1
С
Н
N
6a
6b
6c
6d
C18H15ClN2O2
C18H15BrN2O2
C19H17NO2
66.28
66.16
58.31
58.24
78.52
78.33
65.72
65.31
4.52
4.63
4.10
4.07
5.76
5.88
4.47
4.93
8.64
8.57
7.59
7.55
4.69
4.81
11.11
11.42
159-160
139-140
98-102
0.63
0.67
0.53
0.43
3355 (NH)
3347 (NH)
3310 (NH)
C20H18ClN3O2
178-180
3380 (NH),
1674 (NCO)
3409 (NH),
1673 (NCO)
3396 (OH)
6e
C21H20N2O2
75.72
75.88
6.47
6.06
8.11
8.43
161-163
0.52
7a
7b
7c
8а
8b
8c
9
C15H13NO2
75.41
75.30
70.22
70.03
75.67
75.87
66.81
66.57
59.01
58.56
80.17
78.87
80.08
79.98
68.32
68.46
5.59
5.48
4.98
4.70
6.07
5.97
3.65
4.03
3.65
3.55
5.15
5.23
4.62
4.65
3.19
3.23
5.53
5.85
5.35
5.44
5.32
5.53
8.16
8.63
7.16
7.59
5.01
4.84
7.26
7.17
10.27
9.98
58-60
0.32
0.54
0.21
0.59
0.48
0.70
0.62
0.41
—
C15H12FNO2
C16H15NO2
58-59
3230 (OH)
3420 (ОH)
3381 (ОН)
3225 (ОН)
3372 (ОН)
1595 (C=C)
—
—
C18H13ClN2O2
C18H13BrN2O2
C18H13BrN2O2
C13H9NO
202-205
146-148
135-136
58-59
10
13
C16H9ClN2O
C16H17NO4
156-158
195-197
66.79
66.89
5.54
5.96
4.95
4.88
3433 (ОH),
1682 (СO2H)
_______
*Solvents: ethyl acetate–hexane, 1:6 (6a, 9), 1:4 (6b) 1:8 (6c), 1:2 (6d,
7a,b), 1:1 (7c, 8c); ethyl acetate (6e), ethyl acetate–ethanol, 8:1 (8a,b, 10).
The presence of a pyridine nitrogen atom in starting Schiff bases 5a,b was found, on the whole, not to
affect the conditions for the cycloaddition, which was carried out in toluene at 20°C over 24 h with
~10 mole % BF3·Et2O, but sharply lowered the yield of products 6 in comparison with quinolines 2-4.
Combinations of other solvents such as acetonitrile, ether, and benzene and other catalysts such as aluminum
chloride, tin chloride, titanium chloride, and p-TsOH and an increased Schiff base-catalyst ratio were also tested
in the reaction. The yield of phenanthrolines 6 could not be increased over 30% in any case and an increased
mole fraction of the Lewis acid only increased the amount of polymer impurities.
In the second part of this work, we studied the behavior of the tetrahydroquinoline ring in adducts 2-6 in
the presence of various oxidizing agents.
Condensed tetrahydrofuran and tetrahydropyran fragments in 2a,b, 3, and 6a-c proved unstable upon the
action of various reagents. 2-Furyl-3-hydroxyalkylquinolines 7a-c, 2-furyl-1,10-phenanthrolines 8a,b, and
2-furylbenzoquinoline 8c were formed upon heating quinolines 2a, 3, and 6a-c at reflux in nitrobenzene as the
result of opening of the fused oxo fragment at the C(4)–O bond and aromatization of the tetrahydropyridine ring.
Quinolines 7a-c were also obtained upon heating furoquinolines 2a,b, and 3 with sulfur in DMF at reflux, in the
reaction of furo- and pyranoquinolines 2a and 3 with 2 N hydrochloric acid in acetonitrile at 50°C, and in the
potassium permanganate oxidation of 2a in the presence of DB18C6 crown ether. The primary hydroxyl group
and 2-furyl substituent in quinolines 7a-c and phenanthrolines 8a-c were not affected in the oxidation.
310

O
N
OH
OH
R
PhNO2
X
( )n
O
[O]
6a–c
2a,b, 3
N
R
8 a–c (62–69%)
7 a–c (30–84 %)
7 a R = H, n = 1; b R = F, n = 1; c R = H, n = 2; 8 a R = Cl, X = N, b R = Br, X = N, c R = H, X = CH
The oxidation of 4-pyrrolidonyltetrahydroquinolines 4 by sulfur in DMF at reflux, by potassium
permanganate under phase-transfer catalysis conditions, or by nitrobenzene at reflux is accompanied by the
elimination of the pyrrolidone fragment such that 2-furylquinoline (9) is formed in 40-70% yield. Analogously,
4-pyrrolidonyltetrahydrophenanthroline 6d is converted upon heating in nitrobenzene at reflux into 2-furyl-
1,10-phenanthroline 10.
We note that products of the elimination of 4-N- and 4-O-alkyl substituents with subsequent
aromatization of the tetrahydroquinoline fragment analogous to quinolines 7 and 9 are often observed as
by-products in the Povarov reaction [9-11] but have not been obtained in preparative reactions. The synthesis of
functional derivatives of 1,10-phenanthrolines such as 8a,b, and 10 has not been studied extensively [12, 13]
although their 9-amino and 9-pyridyl derivatives display useful photoluminescence properties [14] and are
ligands in chromogenic receptors [15, 16].
O
N
N
[O]
PhNO2
4
6d
O
N
Cl
10 (46%)
9 (40–70%)
Adduct 12 formed in the cycloaddition of aldimine 11 to dihydrofuran in the presence of BF3·OEt2
could not be isolated since this compound spontaneously is converted to furylquinolinecarboxylic acid 13 as the
result of opening of the tetrahydrofuran fragment.
O
O
OH
O
O
N
N
H
O
BF3· OEt2
MeCN
N
CO2H
CO2H
CO2H
11
12
13 (20%)
Acetonitrile was used as the solvent in the latter case in light of the low solubility of aldimine 11 in
toluene.
311

TABLE 2. 1H NMR Spectra of Compounds 6-10 and 13
Com-
Chemical shifts, δ, ppm (J, Hz)
pound
1
2
6a*
1.65 (br. s, NH); 1.94 (1Н, m, Н-1В); 2.37 (1Н, m, Н-1А);
3.18 (1Н, ddq, J = 3.2, J = 8.5, J = 1.7, Н-11а); 3.85-3.73 (2Н, m, Н-2А+Н-2В);
4.77 (1Н, d, J = 3.2, Н-11); 6.45-6.39 (2Н, m, Н-3'+Н-4'); 6.50 (1Н, d, J = 8.5, Н-3а);
7.24 (1Н, s, Н-5); 7.39 (1Н, dd, J = 4.2, J = 8.3, Н-7); 7.43 (1Н, dd, J = 0.8, J = 1.7, Н-5');
7.96 (1Н, dd, J = 8.3, J = 1.6, Н-6); 8.71 (1Н, dd, J = 4.2, J = 1.6, Н-8)
6b*
6c*
1.95 (1Н, m, Н-1В); 2.37 (1Н, dq, J = 12.4, J = 8.3, Н-1А);
3.18 (1Н, ddq, J = 3.4, J = 8.3, J = 2.0, Н-11а); 3.75 (1Н, dt, J = 8.1, J = 8.3, Н-2В);
3.83 (1Н, q, J = 8.0, Н-2А); 4.77 (1Н, br. s, J = 3.4, Н-11); 6.45-6.39 (2Н, m, Н-3'+Н-4');
5.55 (1Н, d, J = 8.4, Н-3а); 7.47 (1Н, s, Н-5); 7.39 (1Н, dd, J = 4.2, J = 8.3, Н-7);
7.43 (1Н, dd, J = 0.8, J = 1.6, Н-5'); 7.96 (1Н, dd, J = 8.3, J = 1.6, Н-6);
8.73 (1Н, dd, J = 4.2, J = 1.6, Н-8)
1.93 (1Н, m, Н-1В); 2.29 (1Н, dq, J = 12.5, J = 8.5, Н-1А);
3.06 (1Н, dq, J = 2.9, J = 8.3, Н-11а); 3.71 (1Н, dt, J = 8.5, J = 4.7, Н-2В);
3.84 (1Н, q, J = 8.0, Н-2А); 4.66 (br. s, NH); 4.84 (1Н, d, J = 2.9, Н-11);
5.44 (1Н, d, J = 7.8, Н-3а); 6.40 (1Н, br. dd, J = 0.7, J = 3.1, Н-3');
6.44 (1Н, dd, J = 1.8, J = 3.1, Н-4'); 7.34 (1Н, d, J = 8.4, Н-9);
7.44-7.48 (2Н, m, Н-4+Н-5); 7.48 (1Н, dd, J = 0.7, J = 1.8, Н-5');
7.76-7.80 (3Н, m, Н arom)
6d
6e
7a
1.56 (1Н, m, Н-4"В); 1.74 (1Н, m, Н-4"А); 2.37-2.23 (2Н, m, Н-3");
2.42 (1Н, ddd, J = 1.0, J = 5.7, J = 14.0, Н-3В); 2.62 (1Н, m, Н-5"В);
2.73 (1Н, m, Н-5"А); 2.86 (1Н, ddd, J = 0.7, J = 5.7, J = 14.0, Н-3А); 4.84 (1Н, m, Н-2);
5.57 (1Н, t, J = 5.7, Н-4); 6.24 (1Н, dd, J = 0.6, J = 3.2, Н-3');
6.31 (1Н, dd, J = 1.8, J = 3.2, Н-4'); 7.11 (1Н, s, Н-6); 6.86 (br. s, NH);
7.38 (1Н, dd, J = 0.6, J = 1.8, Н-5'); 7.41 (1Н, dd, J = 8.4, J = 4.3, Н-8);
7.95 (1Н, dd, J = 1.6, J = 8.4, Н-7); 8.72 (1Н, dd, J = 1.6, J = 4.3, Н-9)
2.07-1.99 (2Н, m, Н-4"); 2.39 (1Н, dt, J = 11.0, J = 12.2, Н-3ах);
2.41 (1Н, ddd, J = 3.3, J = 7.0, J = 12.2, Н-3eq); 2.63-2.48 (2Н, m, Н-3");
3.09 (1Н, dt, J = 9.7, Н-5"В); 3.26 (1Н, dt, J = 9.7, Н-5"А); 4.74 (br. s, NH);
4.79 (1Н, dd, J = 3.3, J = 11.0, Н-2); 5.89 (1Н, dd, J = 7.0, J = 11.0, Н-4);
6.39 (1Н, dd, J = 3.2, J = 0.6, Н-3'); 6.43 (1Н, dd, J = 1.8, J = 3.2, Н-4');
7.05 (1Н, d, J = 8.4, Н-6); 7.28 (1Н, d, J = 8.4, Н-5), 7.45 (1Н, dd, J =0.6, J = 1.8, Н-5');
7.48-7.45 (2Н, m, Н-7+Н-10); 7.79-7.75 (2Н, m, Н-8+Н-9)
1.87 (1Н, br. s, ОH); 3.28 (2Н, t, J = 6.4, Н-1"); 3.93 (2Н, t, J = 6.4, Н-2");
6.54 (1Н, dd, J = 1.7, J = 3.2, Н-4'); 7.11 (1Н, d, J = 3.2, Н-3');
7.43 (1Н, dd, J = 7.5, J = 8.2, Н-7); 7.57 (1Н, dd, J = 0.8, J = 1.7, Н-5');
7.62 (1Н, br. t, J = 7.5, Н-6); 7.63 (1Н, d, J = 7.5, Н-5); 7.96 (1Н, s, Н-4);
8.04 (1Н, d, J = 8.2, Н-8)
7b
7c
2.01 (1Н, br. s, OH); 3.32 (2Н, t, J = 6.4, Н-1"); 3.96 (2Н, t, J = 6.4, Н-2");
6.58 (1Н, dd, J = 1.8, J = 3.4, Н-4'); 7.12 (1Н, dd, J = 0.8, J = 3.4, Н-3');
7.30 (1Н, dd, J = 2.8, J = 8.8, Н-5); 7.42 (1Н, ddd, J = 9.2, J = 2.8, J = 8.4, Н-7);
7.61 (1Н, dd, J = 0.8, J = 1.8, Н-5'); 7.95 (1Н, s, Н-4); 8.04 (1Н, dd, J = 5.4, J = 9.2, Н-8)
1.62 (1Н, br. s, ОH); 1.94 (2Н, m, Н-2"); 3.18 (2Н, t, J = 7.7, Н-3");
3.75 (2Н, t, J = 6.2, Н-1"); 6.59 (1Н, dd, J = 1.7, J = 3.2, Н-4');
7.16 (1Н, dd, J = 0.8, J = 3.2, Н-3'); 7.49 (1Н, ddd, J = 1.1, J = 6.9, J = 8.2, Н-7);
7.63 (1Н, dd, J = 0.8, J = 1.7, Н-5'); 7.66 (1Н, ddd, J = 1.0, J = 6.9, J = 8.3, Н-6);
7.74 (1Н, dd, J =1.1, J =8.3, Н-5); 8.00 (1Н, s, Н-4); 8.11 (1Н, dd, J = 1.0, J = 8.2, Н-8)
8а
8b
8c
3.35 (1Н, t, J = 5.2, Н-1"В); 3.79 (2Н, q, J = 5.2, Н-2"); 4.85 (1Н, t, J = 5.2, Н-1"А);
6.78 (1Н, dd, J = 3.2, J = 1.7, Н-4'); 7.37 (1Н, dd, J = 0.8, J = 3.2, Н-3');
7.78 (1Н, dd, J = 8.1, J = 4.2, Н-8); 8.01 (1Н, dd, J = 0.8, J = 1.7, Н-5'); 8.20 (1Н, s, Н-6);
8.44 (1Н, dd, J = 1.6, J = 8.1, Н-7); 8.53 (1Н, s, Н-4); 9.12 (1Н, dd, J = 1.6, J = 4.2, Н-9)
1.88 (1Н, br. s, ОH); 3.45 (2Н, t, J = 6.4, Н-1"); 4.11 (2Н, t, J = 6.4, Н-2");
6.61 (1Н, dd, J = 3.3, J = 1.7, Н-4'); 7.43 (1Н, br. s, J = 3.3, Н-3');
7.62 (1Н, dd, J = 8.1, J = 4.3, Н-8); 7.63 (1Н, br. s, J = 1.7, Н-5'); 7.93 (1Н, s, Н-6);
8.12 (1Н, dd, J = 1.5, J = 8.1, Н-7); 8.33 (1Н, s, Н-4); 9.17 (1Н, dd, J = 1.5, J = 4.3, Н-9)
1.49 (1H, br. s, ОH); 3.46 (2Н, t, J = 6.5, Н-2"); 4.01 (2Н, dd, J = 4.8, J = 6.5, Н-2");
6.63 (1Н, dd, J = 3.1, J = 1.9, Н-4'); 7.41 (1Н, br. s, J = 3.1, Н-3');
7.62 (1Н, d, J = 8.7, Н-5); 7.63 (1Н, br. s, J = 1.9, Н-5'); 7.66 (1Н, dt, J = 1.2, J = 6.9, Н-8);
7.71 (1Н, dt, J = 1.0, J = 6.9, Н-9); 7.75 (1Н, d, J = 8.7, Н-6); 8.04 (1Н, s, Н-4);
9.32 (1Н, d, J = 7.5, Н-10)
312

TABLE 2 (continued)
1
2
9
6.59 (1Н, dd, J = 1.8, J = 3.4, Н-4'); 7.22 (1Н, dd, J = 0.8, J = 3.4, Н-3');
7.50 (1Н, ddd, J = 1.2, J = 6.9, J = 8.0, Н-7); 7.64 (1Н, dd, J = 0.8, J = 1.8, Н-5');
7.71 (1Н, ddd, J = 1.6, J = 6.9, J = 8.2, Н-6); 7.78 (1Н, dd, J = 1.2, J = 8.2, Н-5);
7.82 (1Н, d, J = 8.6, Н-3), 8.13 (1Н, ddd, J = 1.1, J = 1.6, J = 8.0, Н-8);
8.16 (1Н, br. s, J = 8.6, Н-4)
10
13
6.63 (1Н, dd, J = 3.4, J = 1.8, Н-4'); 7.52 (1Н, br. s, J = 3.4, Н-3');
7.64 (1Н, dd, J7,8 = 8.1, J = 4.3, Н-8); 7.67 (1Н, dd, J = 0.6, J = 1.8, Н-5'); 7.85 (1Н, s, Н-6);
8.14 (1Н, d, J = 8.7, Н-3); 8.16 (1Н, dd, J = 8.1, J = 1.6, Н-7); 8.69 (1Н, d, J = 8.7, Н-4);
9.20 (1Н, dd, J = 1.6, J = 4.3, Н-9)
1.87 (1H, br. s, OН); 3.44 (2Н, t, J = 6.0, Н-1"); 4.11 (2Н, t, J = 6.0, Н-2");
6.67 (1Н, dd, J = 1.7, J = 3.4, Н-4'); 7.24 (1Н, br. s, J = 3.4, Н-3');
7.57 (1Н, dd, J = 8.2, J = 7.1, Н-6); 7.71 (1Н, dd, J = 1.7, J = 0.7, Н-5');
7.99 (1Н, dd, J = 1.2, J = 8.2, Н-5); 8.32 (1Н, s, Н-4); 8.54 (1Н, dd, J = 1.2, J = 7.1, Н-7)
_______
* Data are given for the predominant cis isomers of 6a-c isolated as pure compounds.
TABLE 3. Mass Spectra of Compounds 6-10 and 13
Com-
pound
m/z (Irel, %)
6a
6b
6c
326 [М]+ (for 35Cl) (62), 281 (61), 255 (11), 229 (12), 215 (52), 202 (14), 191 (12),
140 (14), 126 (12), 114 (11), 91 (14), 81 (100), 77 (26), 62 (16), 51 (29), 39 (77)
372 [М]+ (for 79Br) (34), 327 (36), 261 (33), 247 (12), 218 (11), 180 (13), 166 (12),
140 (12), 128 (13), 115 (12), 102 (12), 91 (18), 81 (100), 65 (14), 51 (13), 39 (83)
291 [М]+ (100), 260 (11), 246 (59), 217 (12), 180 (19), 167 (15), 139 (7), 115 (14),
91 (13), 77 (18), 55 (7), 39 (20)
6d
6e
7a
367 [М]+ (for 35Cl) (2), 281 (100), 253 (6), 218 (9), 191 (2), 140 (2), 126 (3), 81 (3), 41 (2)
332 [М]+ (11), 246 (100), 217 (11), 180 (8), 167 (4), 151 (4), 127 (3), 81 (5), 41 (2)
239 [М]+ (80), 222 (25), 208 (42), 180 (100), 152 (20), 89 (13), 77 (11), 63 (13),
51 (9), 39 (15)
7b
7c
8а
8b
257 [М]+ (84), 240 (28), 226 (33), 212 (13), 198 (100), 186 (11), 170 (17), 151 (7), 99 (8),
57 (8), 39 (12)
235 [М–H2O]+ (33), 218 (100), 206 (72), 192 (24), 181 (22), 152 (8), 136 (5), 115 (6),
102 (7), 39 (3)
324 [M]+ (for 35Cl) (83), 307 (14), 293 (31), 279 (14), 265 (100), 253 (14), 229 (34),
203 (13), 164 (7), 101 (5), 31 (4)
368 [M]+ (69), 351 (17), 339 (36), 311 (73), 297 (15), 229 (100), 203 (23), 164 (14),
101 (9), 31 (7)
8c
9
289 [M]+ (87), 258 (49), 230 (100), 202 (26), 165 (7), 114 (10), 88 (9), 51 (9)
195 [М]+ (100), 167 (30), 139 (16), 128 (7), 101 (4), 75 (5), 63 (6), 51 (5), 39 (7)
280 [M]+ (for 35Cl) (100), 252 (39), 216 (18),189 (7), 140 (8), 126 (6), 95 (5)
283 [М]+ (7), 239 (100), 207 (12), 192 (7), 180 (16), 152 (7), 127 (3), 44 (8)
10
13
Thus, promising intermediates for the preparation of polydentate ligands, namely,
2-furyl-1,10-phenanthrolines, were synthesized for the first time by the Povarov reaction in this work. The
reaction of furfurylidene-8-aminoquinolines with electron-rich alkenes was shown to proceed in the presence of
catalytic amounts of a Lewis acid. The oxidation of 4-N- and 4-O-alkyl-substituted and furocondensed
2-furyl-1,2,3,4-tetrahydroquinolines and phenanthrolines by nitrobenzene and elemental sulfur was found to
give high yields of the products of aromatization with prior elimination of the N-alkyl or O-alkyl substituent.
313

EXPERIMENTAL
Reagents obtained from Acros Organics were used without further purification. Freshly distilled
solvents were used for the syntheses. The melting points of the products were measured on an SMP 10
instrument and not corrected. The IR spectra were taken on an Infralum FT-801 IR Fourier spectrometer in KBr
1
pellets. The H NMR spectra were taken on a Bruker WH-400 spectrometer at 400 MHz at 26°C for ~3%
solutions in CDCl3 with residual CHCl3 as the internal standard. Some of the electron impact mass spectra were
obtained on a Thermo Focus DSQ II GC/MS at 70 eV with direct inlet. The ion source temperature was 200°C.
A Varian FactorFour VF-5ms chromatographic column was used. Other electron impact mass spectra were taken
on a Thermo Trace DSQ mass spectrometer at 70 eV with direct inlet. The ion source temperature was 200°C.
Plates coated with Sorbfil PTSKh-AF-A-UF-254 were used for the thin-layer chromatography with development
by iodine vapor. The purification of the final products was carried out on activated neutral 50-200 mesh alumina
or by recrystallization from hexane–ethyl acetate. The isomer ratio in the reaction products was found from the
1H NMR spectra as the ratio of the integral intensities of monotypic proton signals.
The physicochemical characteristics and elemental analysis data of all the new compounds are given in
Table 1, while the 1H NMR spectral data are given in Table 2 and the mass spectra are given in Table 3.
5-Chloro-1,2,3a,10,11,11a-hexahydro- (6a) and 6-Bromo-1,2,3a,10,11,11a-hexahydro-11-(2-furyl)furo-
[3,2-c]-1,10-phenanthrolines (6b), 11-(2'-Furyl)-1,2,3a,10,11,11a-hexahydrobenzo[H]furo[3,2-c]quinoline (6c),
5-Chloro-2-(2-furyl)-4-(N-2-oxopyrrolidinyl)-(2S*,4S*)-1,2,3,4-tetrahydro-1,10-phenanthroline
(6d),
2-(2-Furyl)-4-(N-2-oxopyrrolidinyl)benzo-(2S*,4S*)-1,2,3,4-tetrahydro[H]quinoline (6e) (General Method).
A sample of BF3·OEt2 (0.11 ml, 0.84 mmol) and then dihydrofuran (for 6a-c) (2.8 ml, 40 mmol) or
N-vinyl-2-pyrrolidone (for 6d,e) (4.3 ml, 40 mmol) were added to a stirred solution of azomethine 5a-c
(30 mmol) in dry toluene (50 ml) at 25°C and stirred for 24 h at 20°C with monitoring by thin-layer
chromatography. Then, 3-4 ml 25% aqueous ammonia was added and the solvent was removed in vacuum. The
viscous brown oily residue was purified by column chromatography using 1:5 ethyl acetate–hexane as the
eluent. Phenanthrolines and benzoquinolines 6a-e were obtained as white crystals.
The recrystallization solvents were toluene for 6a,b,d, and 6e and benzene for 6c. The yields and
trans/cis diastereomer ratios were: 6a – 28%, 40:60; 6b – 21%, 45:55; 6c – 48%, 50:50; the yields of cis-6d and
cis-6d were 100%.
2'-[2-(2-Furyl)-3-quinolinyl]-1'-ethanol (7a) and 2'-[6-Fluoro-2-(2-furyl)-3-quinolinyl]-1'-ethanol
(7b). A. Dibenzo-18-crown-6 (0.072 g, 0.2 mmol) and potassium permanganate (1.30 g, 8.3 mmol) were added
to a solution of tetrahydroquinoline 2a (1.00 g, 4.15 mmol) in dichloromethane (100 ml) and stirred for 4 h at
~20°C with monitoring by thin-layer chromatography. The manganese(IV) oxide formed was filtered off and
washed with two dichloromethane portions (30 ml). The solution was evaporated to dryness. Then, 10 ml ether
was added to the residue and the crown ether residue was filtered off. The yellow oily residue was subjected to
chromatography on a 45×1 cm column, which was eluted consecutively with 1:10, 1:5, and 1:1 ethyl acetate–
hexane to give 0.47 g (49%) quinoline 7a as light-brown crystals, mp 58-60°C.
B. Tetrahydroquinoline 2a (1.0 g, 4.15 mmol) in nitrobenzene (15 ml) was heated at reflux for 10 h.
The solvent was removed in vacuum. The black oily residue was subjected to chromatography on a 25×4 cm
column using 1:10 ethyl acetate–hexane as the eluent to give 0.81 g (82%) quinoline 7a, mp 59-61°C. This
product mixed with a sample obtained by Method A did not give a depressed melting point.
C. A mixture of sulfur powder (1.60 g, 49 mmol) and amine 2a or 2b (16.5 mmol) was heated at reflux
for 4 h until hydrogen sulfide was no longer evolved. The reaction mixture was poured into water (50 ml) and
extracted with three chloroform portions (50 ml). The combined organic extracts were dried over magnesium
sulfate. After removal of the solvent, the dark-brown oil was subjected to chromatography on a 25×4 cm column
using ether as the eluent to give 2.00 g (50%) quinoline 7a as brown crystals, mp 60-62°C or 1.27 g (30%)
quinoline 7b as light-beige crystals.
314

D. 2 N Hydrochloric acid (2 ml) was added to a solution of tetrahydroquinoline 2a (0.22 g, 0.9 mmol)
in acetonitrile (20 ml). The reaction mixture was maintained for 2 h at 50°C with monitoring by thin-layer
chromatography. The solution was poured into water (20 ml), neutralized by adding 25% ammonium
hydroxide, and extracted with three portions of ethyl acetate (25 ml). The combined organic extracts were dried
over magnesium sulfate. Removal of the solvent gave 0.18 g (84%) quinoline 7a as light-yellow crystals,
mp 60-61°C.
3'-[2-(2-Furyl)-3-quinolinyl]-1'-propanol (7c). A. Dibenzo-18-crown-6 (0.21 g, 0.6 mmol) and
potassium permanganate (2.46 g, 15.6 mmol) were added to a solution of tetrahydroquinoline 3 (1.00 g,
3.9 mmol) in dichloromethane (100 ml) and stirred for 24 h at ~20°C with monitoring by thin-layer
chromatography. The manganese(IV) oxide formed was filtered off and washed with two 30 ml
dichloromethane portions. The solution was evaporated to dryness. The residue was subjected to
chromatography on a 45×1 cm column with 1:10 ethyl acetate–hexane as the eluent to give 0.36 g (37%)
quinoline 7c as a yellow oil, which darkens upon standing in the air.
B. A mixture of sulfur powder (0.38 g, 12 mmol) and amine 3 (1.00 g, 3.9 mmol) in DMF (20 ml) was
heated at reflux until no further hydrogen sulfide evolved with monitoring by thin-layer chromatography. The
reaction mixture was poured into water (30 ml) and extracted with three 30-ml chloroform portions. The
combined organic extracts were dried over magnesium sulfate. After removal of the solvent, the dark-brown oily
residue was purified on a 25×4 cm column using 1:10 ethyl acetate–hexane as the eluent to give 0.60 g (61%)
quinoline 7c.
C. 2 N Hydrochloric acid (4.4 ml) was added to a solution of tetrahydroquinoline 3 (1.0 g, 3.9 mmol) in
acetonitrile (40 ml) and maintained for 2 h at 50°C with monitoring by thin-layer chromatography. The solution
was poured into 40 ml water, neutralized with 25% ammonium hydroxide, and extracted with three portions of
ethyl acetate (30 ml). The combined organic extracts were dried over magnesium sulfate. After removal of the
solvent, the dark oil was purified on a 25×4 cm column using 1:10 ethyl acetate–hexane as the eluent to give
0.32 g (32%) quinoline 7c as a light-yellow oil.
2'-[2-(2-Furyl)-1,10-phenanthrolin-3-yl]-1'-ethanols 8a,b and 2'-[2-(2-Furyl)benzoquinolin-
3-yl]-1'-ethanol 8c (General Method). A mixture of corresponding phenanthroline 6a-c (4.82 mmol) and
nitrobenzene (27 ml, 260 mmol) was heated at reflux for 6 h with monitoring by thin-layer chromatography.
Nitrobenzene was distilled off and the remaining black oil was subjected to chromatography on a 30×5 cm
column with gradient elution from hexane to 1:10 and 1:5 ethyl acetate–hexane and, finally, ethyl acetate to give
alcohols 8a (in 66% yield), 8b (in 62% yield), and 8c (in 69% yield) as white crystals.
2-(2-Furyl)quinoline (9). A. A solution of tetrahydroquinoline 4 (54 mmol) and sulfur (5.12 g,
160 mmol) in DMF (50 ml) was heated at reflux until no further hydrogen sulfide evolved with monitoring by
thin-layer chromatography. The reaction mixture was poured into water (50 ml) and extracted with three
portions of ethyl acetate (50 ml). The combined organic extracts were dried over magnesium sulfate. The solvent
was evaporated in vacuum and the dark oily residue was purified by column chromatography using
1:10 ethyl acetate–hexane as the eluent to give 7.39 g (70%) quinoline 9.
B. Potassium permanganate (1.12 g, 7.08 mmol) was added to a solution of tetrahydroquinoline 4
(3.54 mmol) and dibenzo-18-crown-6 (0.06 g, 0.18 mmol) in chloroform (50 ml) and stirred at room
temperature for 4 h with monitoring by thin-layer chromatography. The manganese (IV) oxide formed was
filtered off and washed with two 30 ml chloroform portions. The solvent was evaporated at reduced pressure and
the brown oily residue was purified by column chromatography using ether as the eluent to give 0.13 g (19%)
quinoline 9.
C. A solution of tetrahydroquinoline 4 (3.54 mmol) in nitrobenzene (15 ml) was heated at reflux for 7 h
with monitoring by thin-layer chromatography. Nitrobenzene was distilled off in vacuum and the remaining
black oil was subjected to column chromatography using 1:10 ethyl acetate–hexane as the eluent to give 0.14 g
(20%) quinoline 9.
315

5-Chloro-2-(2-furyl)-1,10-phenanthroline (10). A mixture of 2-(2-furyl)phenanthroline 6d (1.00 g,
2.7 mmol) and nitrobenzene (15 ml, 150 mmol) was heated at reflux for 6 h with monitoring by thin-layer
chromatography. Nitrobenzene was distilled off in vacuum. The dark oily residue was subjected to
chromatography on a 25×2 cm column with gradient elution starting with hexane, then 1:10, 1:5,
1:2 ethyl acetate–hexane, and finally ethyl acetate to give 0.35 g (46%) phenanthroline 10 as light-brown
crystals.
3-(2-Hydroxyethyl)-2-(2-furyl)quinoline-8-carboxylic acid (13). A sample of BF3·OEt2 (0.3 ml,
25 mmol) and then dihydrofuran (7.6 ml, 100 mmol) were added to a stirred solution of azomethine 11
(100 mmol) in dichloromethane (100 ml). The reaction mixture was stirred for 24 h at room temperature. At the
end of the reaction, three or four drops of 25% ammonium hydroxide were added and the solvent was
evaporated off in vacuum. The residue was recrystallized from ethyl acetate–hexane to give 2.92 g (20%)
furylquinoline 13 as white prisms.
This work was carried out with the financial support of the Russian Basic Research Fund,
Grant 07-03-00083a.
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