3894
A. S. Degtyarenko et al.
PAPER
13C NMR: d = 17.2 (2-CH2), 27.0 (1-CH2), 31.0 (3-CH2), 57.1 (4-
CHCl), 124.8 (7-C), 125.4 (8-C), 126.7 (8a-C), 127.9 (6-C), 129.1
(C6H5, 2,6-CH), 129.4 (C6H5, 4-CH), 129.6 (C6H5, 3,5-CH), 129.8
(9a-C), 132.6 (C6H5, 1-C), 135.3 (5-C), 141.5 (9-C), 153.6 (10a-C),
153.8 (4a-C).
1H NMR: d = 2.92 (s, 3 H, CH3), 4.45 (s, 2 H, CH2), 7.81 (dd,
J = 8.4, 7.2 Hz, 1 H, 7-H), 7.96 (dd, J = 8.0, 7.2 Hz, 1 H, 6-H), 8.30
(d, J = 8.0 Hz, 1 H, 5-H), 8.43 (d, J = 8.4 Hz, 1 H, 8-H).
13C NMR: d = 15.7 (CH3), 26.6 (CH2), 117.4 (CN), 124.5 (6-C),
126.6 (7-C), 127.6 (4a-C), 128.0 (5-C), 129.5 (8-C), 130.4 (3-C),
142.8 (4-C), 144.9 (8a-C), 149.1 (2-C).
Anal. Calcd for C19H16ClN·HCl: C, 69.10; H, 5.19; N, 4.24; Cl,
21.47. Found: C, 68.93; H, 5.18; N, 4.49; Cl, 21.57.
Anal. Calcd for C12H9ClN2: C, 66.52; H, 4.19; N, 12.93; Cl, 16.36.
Found: C, 66.50; H, 4.13; N, 12.86; Cl, 16.40.
4,7-Dichloro-1,2,3,4-tetrahydro-9-phenylacridine Hydrochlo-
ride (4c)
Mp 171–172 °C (i-PrOH).
2-(Aminomethyl)quinolines 6a,b; General Procedure
A solution of compound 3a,b (0.016 mol) and the corresponding
amine (0.05 mol) in DMF (20 mL) was stirred for 4 h at 50 °C. The
solvent was removed in vacuo and the residue was treated with H2O
(20 mL) to give an oily material which slowly solidified over the
course of a day. It was filtered and recrystallized from an appropri-
ate solvent to afford derivatives 6a,b.
1H NMR: d = 1.87 (m, 1 H, 2-H), 2.14 (m, 1 H, 3-H), 2.37 (m, 2 H,
2,3-H), 2.66 (m, 2 H, 1-CH2), 5.59 (s, 1 H, 4-CHCl), 7.19 (s, 1 H, 8-
H), 7.39 (d, J = 7.0 Hz, 2 H, C6H5, 2,6-H), 7.60 (m, 3 H, C6H5, 3,4,5-
H), 7.76 (d, J = 8.4 Hz, 1 H, 6-H), 8.10 (d, J = 8.4 Hz, 1 H, 5-H),
10.45 (br s, 1 H, N·HCl).
13C NMR: d = 17.5 (2-CH2), 27.3 (1-CH2), 31.8 (3-CH2), 60.1 (4-
CHCl), 123.1 (8-C), 124.6 (8a-C), 128.3 (6-C), 129.3 (C6H5, 2.6-
CH), 129.4 (C6H5, 4-CH), 129.7 (C6H5, 3,5-CH), 130.6 (9a-C),
131.0 (C6H5, 1-C), 132.7 (7-C), 135.5 (5-C), 143.8 (9-C), 148.5
(10a-C), 156.2 (4a-C).
4-Methyl-2-(4-morpholinylmethyl)-3-quinolinecarboxylic Acid
Ethyl Ester (6a)
Yield: 4.02 g (80%), mp 153 °C (i-PrOH).
1H NMR: d = 1.43 (t, J = 7.2 Hz, 3 H, CH3), 3.50 (m, 4 H, NCH2),
3.95 (m, 4 H, OCH2), 4.47 (q, J = 7.2 Hz, 2 H, OCH2), 4.75 (s, 2 H,
CH2N), 7.75 (dd, J = 8.4, 7.6 Hz, 1 H, 7-H), 7.92 (dd, J = 8.4, 7.6
Hz, 1 H, 6-H), 8.12 (d, J = 8.4 Hz, 1 H, 5-H), 8.25 (d, J = 8.4 Hz, 1
H, 8-H).
13C NMR: d = 14.4 (CH3), 16.3 (CH3), 52.5 (NCH2), 58.1 (2-CH2),
62.7 (OCH2), 63.7 (2 OCH2), 125.5 (6-C), 125.9 (7-C), 126.4 (4a-
C), 128.5 (5-C), 129.5 (3-C), 131.8 (8-C), 145.2 (4-C), 145.9 (8a-
C), 147.5 (2-C), 167 (COO).
Anal. Calcd for C19H15Cl2N·HCl: C, 62.57; H, 4.42; N, 3.84; Cl,
29.16. Found: C, 62.50; H, 4.51; N, 3.85; Cl, 29.35.
2-Quinolineacetonitriles 5a–c; General Procedure
Powdered KCN (0.5 g, 8.7 mmol) was added to a solution of 3a–c
(4 mmol) in DMF (10 mL) and the resulting mixture was stirred for
3 h at 45 °C. The inorganic materials were removed by filtration and
the solvent was evaporated to dryness in vacuo. The residue was
treated with H2O (30 mL), filtered, and recrystallized from i-PrOH
to yield derivatives 5a–c.
Anal. Calcd for C18H22N2O3: C, 68.77; H, 7.05; N, 8.91. Found: C,
68.83; H, 6.85; N, 9.14.
2-Cyanomethyl-4-methyl-3-quinolinecarboxylic Acid Methyl
Ester (5a)
Yield: 0.94 g (98%); mp 101–102 °C (i-PrOH).
4-Methyl-2-(1-piperidinylmethyl)-3-quinolinecarboxylic Acid
Methyl Ester (6b)
Yield: 4.19 g (88%); mp 75 °C (MeOH).
1H NMR: d = 2.72 (s, 3 H, CH3), 4.00 (s, 3 H, OCH3), 4.18 (s, 2 H,
CH2), 7.71 (dd, J = 8.4, 7.6 Hz, 1 H, 7-H), 7.84 (dd, J = 8.0, 7.6 Hz,
1 H, 6-H), 8.03 (d, J = 8.0 Hz, 1 H, 5-H), 8.19 (d, J = 8.4 Hz, 1 H,
8-H).
13C NMR: d = 16.3 (CH3), 26.6 (CH2), 53.6 (OCH3), 118.1 (CN),
125.7 (6-C), 126.2 (4a-C), 126.6 (7-C), 128.5 (5-C), 129.8 (3-C),
132.0 (8-C), 145.1 (4-C), 147.0 (8a-C), 148.4 (2-C), 168.3 (COO).
1H NMR: d = 1.41–1.48 (m, 6 H, 3 CH2), 2.30 (m, 4 H, NCH2), 2.68
(s, 3 H, CH3), 3.79 (s, 2 H, CH2N), 3.94 (s, 3 H, OCH3), 7.70 (dd,
J = 8.5, 8.0 Hz, 1 H, 7-H), 7.84 (dd, J = 8.5, 8.0 Hz, 1 H, 6-H), 8.03
(d, J = 8.5 Hz, 1 H, 5-H), 8.20 (d, J = 8.5 Hz, 1 H, 8-H).
13C NMR: d = 15.6 (CH3), 24.1 (CH2), 25.7 (2CH2), 52.0 (OCH3),
54.2 (2 NCH2), 64.9 (2-CH2N), 125.3 (6-C), 126.5 (3-C), 126.9 (4a-
C), 127.0 (7-C), 130.0 (5-C), 130.7 (8-C), 142.2 (4-C), 146.4 (8a-
C), 156.9 (2-C), 168.8 (COO).
Anal. Calcd for C14H12N2O2: C, 69.99; H, 5.03; N, 11.66. Found: C,
69.90; H, 4.87; N, 11.60.
Anal. Calcd for C18H22N2O2: C, 72.46; H, 7.43; N, 9.39. Found: C,
72.46; H, 7.50; N, 9.46.
2-Cyanomethyl-4-phenyl-3-quinolinecarboxylic Acid Ethyl
Ester (5b)
Yield: 1.20 g (95%); mp 90–91 °C (i-PrOH).
2-[(2-Ethoxy-2-oxoethyl)thio]methyl-4-methyl-3-quinoline-
carboxylic Acid Ethyl Ester (6c)
1H NMR: d = 0.89 (t, J = 7.2 Hz, 3 H, CH3), 3.99 (q, J = 7.2 Hz, 2
H, OCH2), 4.45 (s, 2 H, CH2CN), 7.34 (d, J = 6.0 Hz, 1 H, 5-H),
7.53–7.56 (m, 5 H, 6,7-H + C6H5), 7.84 (m, 2 H, C6H5), 8.11 (d,
J = 8.4 Hz, 1 H, 8-H).
13C NMR: d = 13.9 (CH3), 23.3 (CH2), 62.0 (OCH2), 118.4 (CN),
126.1 (C6H5, 2,6-CH), 126.5 (5-C), 127.0 (4a-C), 129.1 (C6H5, 4-
CH), 129.2 (6-C), 129.4 (7-C), 129.6 (C6H5, 3,5-CH), 129.7 (8-C),
132.0 (C6H5, 1-C), 135.6 (3-C), 147.2 (4-C), 148.5 (8a-C), 153.1 (2-
C), 167.3 (COO).
Powdered K2CO3 (31 g, 0.22 mol) was added to a solution of com-
pound 3a (30 g, 0.10 mol) and ethyl mercaptoacetate (14 g, 0.10
mol) in DMF (70 mL) and the resulting mixture was stirred for 4 h
at 40 °C. The solvent was removed in vacuo and the residue was
treated with H2O (50 mL) to give an oil. It was taken into CHCl3 (50
mL), and the CHCl3 layer was washed with H2O (2 × 20 mL), dried
(Na2SO4), and evaporated to dryness in vacuo to yield the pure com-
pound 6c as an oil; yield: 32.96 g (95%).
1H NMR: d = 1.21 (t, J = 7.0 Hz, 3 H, CH3), 1.44 (t, J = 7.2 Hz, 3
H, CH3), 2.67 (s, 3 H, CH3), 3.37 (s, 2 H, CH2), 4.10 (q, J = 7.0 Hz,
2 H, OCH2), 4.18 (s, 2 H, CH2), 4.47 (q, J = 7.2 Hz, 2 H, OCH2),
7.55 (t, J = 7.8 Hz, 1 H, 7-H), 7.70 (t, J = 7.8 Hz, 1 H, 6-H), 8.00
(m, 2 H, 5,8-H).
Anal. Calcd for C20H16N2O2: C, 75.93; H, 5.10; N, 8.85. Found: C,
75.71; H, 5.05; N, 9.02.
3-Chloro-4-methyl-2-quinolineacetonitrile (5c)
Yield: 0.84 g (97%); mp 107–108 °C (i-PrOH).
13C NMR: d = 14.2 (CH3), 14.3 (CH3), 15.9 (CH3), 33.7 (SCH2),
37.4 (SCH2), 61.0 (OCH2), 62.0 (OCH2), 124.5 (6-C), 126.0 (7-C),
Synthesis 2007, No. 24, 3891–3895 © Thieme Stuttgart · New York