Syntheses of 3-aminoquinoline-2,4(1H,3H)-diones

Article abstract of DOI:10.3987/com-02-9522

Reaction of 3-chloro- (2) and 3-bromoquinoline-2,4(1H,3H)-diones (3) with excess of primary alkyl- or arylamines in dimethylformamide provides the corresponding 3-alkyl- or 3-arylamino derivatives (4). Compounds (4) with the primary amino group at the 3 position were best prepared by reaction of 2 with in situ generated ammonia under anhydrous conditions. An alternative approach to the primary amines (4) via reduction of 3-azidoquinoline-2,4(1H,3H)-diones (5) was investigated. The reduction of 5 with zinc in acetic acid gave moderate to good yields of the desired products, while the reaction with triphenylphosphine afforded exclusively 4-hydroxyquinolin-2(1H)-one (1).

Full text of DOI:10.3987/com-02-9522

HETEROCYCLES, Vol. 57, No. 9, 2002, pp. 1659 -1682, Received, 28th May, 2002
SYNTHESES OF 3-AMINOQUINOLINE-2,4(1H,3H)-DIONES#
Stanislav Kafka,a Antonín Klásek,a,* Jiří Polis,a and Janez Košmrljb
aFaculty of Technology, Tomas Bata University in Zlín, 762 72 Zlín, Czech
b
Republic (e-mail: klasek@ft.utb.cz) and Faculty of Chemistry and Chemical
Technology, University of Ljubljana, 1000 Ljubljana, Slovenia
Abstract – Reaction of 3-chloro- (2) and 3-bromoquinoline-2,4(1H,3H)-diones
(3) with excess of primary alkyl- or arylamines in dimethylformamide provides
the corresponding 3-alkyl- or 3-arylamino derivatives (4). Compounds (4) with
the primary amino group at the 3 position were best prepared by reaction of 2 with
in situ generated ammonia under anhydrous conditions. An alternative approach
to the primary amines (4) via reduction of 3-azidoquinoline-2,4(1H,3H)-diones
(5) was investigated. The reduction of 5 with zinc in acetic acid gave moderate to
good yields of the desired products, while the reaction with triphenylphosphine
afforded exclusively 4-hydroxyquinolin-2(1H)-one (1).
Recently, we have demonstrated interesting chemical transformations of 3-hydroxyquinoline-2,4(1H,3H)-
diones (A, Chart). For example, Wittig olefination of A with ethyl (triphenylphosphoranylidene)acetate
proceeded highly stereoselectively to afford E-4-ethoxycarbonylmethylene derivatives (B).1 In some
cases furo[2,3-c]quinoline-2,4(3aH,5H)-diones (C) were obtained, presumably as a result of lactonization
of the minor formed Z-4-isomer of B. The structure of C was confirmed by an independent synthesis via
the intramolecular Wittig reaction.2 On the other hand, under the same reaction conditions as described
for the synthesis of B, 5,8-disubstituted 3-hydroxyquinoline-2,4(1H,3H)-diones (A) underwent a
completely different reaction, yielding primarily products of indoline (D) and benzoxazine (E) structural
type.3 Those have been shown to be formed via the complex molecular rearrangement of A.4,5
The diverse and smooth reactivity of 3-hydroxyquinoline-2,4(1H,3H)-diones (A) prompted us to continue
similar studies on the closely related 3-aminoquinoline-2,4(1H,3H)-diones (4). So far, few examples of 4
have been reported in the literature. Those include 3-amino-6-chloro-1-methyl-3-phenylquinoline-
# Dedicated to Professor Miloslav Ferles, Professor of Prague Institute of Chemical Technology, on the
occasion of his 80th birthday.

2,4(1H,3H)-dione, prepared by acid hydrolysis of the corresponding 3-acetamido derivative, which was
obtained by a rearrangement of 6-chloro-4-hydroxy-3-imino-1-methyl-4-phenyl-3,4-dihydro-1H-
quinolin-2-one.6 In general, ammonolysis of chloro derivatives (2) with aqueous ammonia has been
shown to yield the corresponding 3-hydroxyquinoline-2,4(1H,3H)-diones, and only 3-benzyl substituted
3-chloroquinoline-2,4(1H,3H)-diones (2, R2 = Bn) afforded the desired 3-amino derivative in low yield.7
Several 3-alkyl- and 3-arylquinoline-2,4(1H,3H)-diones having tertiary amino group at the 3 position
were prepared by the reaction of compound (2) or (3) with secondary amines.7,8 To the best of our
knowledge, 3-alkyl- or 3-arylquinoline-2,4(1H,3H)-diones with the secondary amino group at the 3
position (4, R3 = H) have not yet been described. The overall lack of the secondary and especially of the
primary amines (4) led us to investigate different approaches for their syntheses.
Chart
O
EtOOC
H
COR2
O
OCOR2
O
O
OH
R2
OH
R2
O
R2
N
R1
N
R1
O
N
R1
O
N
R1
O
N
R1
O
A
B
C
D
E
RESULTS AND DISCUSSION
Halides (2) and (3) can be conveniently prepared by halogenation of 1 with sulfuryl chloride9,10 or
bromine.9-11 Therefore, the shortest approach to the desired primary and secondary amines (4) was
considered as a halogen substitution of 2 or 3 with ammonia or primary amines, respectively (Scheme 1).
First we examined the reaction of 3-bromo-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (3D) with a 3-
fold excess of primary alkylamines and benzylamine in benzene. Although literature procedures for the
amination of halides (2) and (3) usually require N,N-dimethylformamide (DMF) as the reaction solvent,7
we chose benzene because it can be easily removed from the reaction mixture. The aminations proceeded
well in refluxing benzene, however, the isolation by evaporation of the volatile compounds resulted in
oily materials, from which we were not able to isolate the corresponding amines (4). Therefore, the use of
this solvent was not pursued further. Aminations conducted in DMF took place at room temperature. The
reactions with alkylamines or benzylamine were completed within 24 h, while prolonged reaction times
or elevated temperatures were required for sluggish amination of 2 or 3 with aniline. In most cases, a
simple workup afforded the corresponding amines (4) in 51–92% isolated yield (Table 1). In general and
according to expectations, bromo derivatives (3) reacted faster than chloro analogues (2), however, the
latter afford purer products. Therefore, the use of 3 was not always more beneficial, as judged from the

yields of 4 in Table 1.
Next, we employed the above reaction conditions for the synthesis of analogues (4) (R3 = H), having
primary amino group at 3 position. We found out that by ammonolysis of 2 or 3 with aqueous ammonia in
DMF, only 3-benzyl substituted 3-aminoquinoline-2,4(1H,3H)-dione (4) (R2 = Bn, R3 = H) can be
prepared, while for the synthesis of other primary 3-alkyl-3-amino and 3-aryl-3-amino analogues (4, R2 =
alkyl, aryl, R3 = H) this protocol cannot generally be applied. These results are consistent with the
literature report on the amination of 3-chloroquinoline-2,4(1H,3H)-diones.7
Scheme 1
OH
O
O
X
NHR3
R2
R2
O
R3NH2
R2
O
SO2Cl2 or Br2
N
N
N
O
R1
R1
R1
1
2 (X = Cl)
3 (X = Br)
4, R3 = H, Me, Bu, c-C6H11,
R1 = H, Me, CH2Ph, Ph
R2 = Me, Bu, CH2Ph, Ph
CH2Ph, Ph
Another approach that we attempted for the synthesis of primary amines (4) involved 3-azidoquinoline-
2,4(1H,3H)-diones (5). Literature precedents revealed that 3-chloro compounds (2) smoothly reacted with
sodium azide to form 5;9,12,13 we surmised that 5 would then be easily reduced to the desired 4 (R3 = H).
First, both 2 and 3 were subjected to the reaction with sodium azide. Similarly as described above for the
amination, bromo compounds (3) reacted faster than chloro analogues (2), but also gave significant
amounts of by-products, as judged by TLC analysis of the reaction mixture. As demonstrated in Table 2,
the isolated yields of purified 5 were comparable, whether 2 or 3 were employed in the reaction.
For the reduction of 5 in the next step we first tried to apply the Staudinger reaction.14 , 15 Thus,
triphenylphosphine was slowly added to a stirred solution of 5B (at room temperature or 0 °C), during
which a rapid evolution of gas was observed. To our surprise, careful examination of the reaction mixture
by TLC showed one spot corresponded in Rf to the authentic 3-benzyl-4-hydroxy-2(1H)-quinolone (1B),
being then isolated from the reaction mixture in 90% yield. It is known that triphenylphosphine can cause
debromination of some α-bromo ketones,16 while deazidation of α-azido-β-keto esters has been observed
under completely different conditions – in a radical chain reaction with tributyltin hydride.17 To the best
of our knowledge, similar deazidation of α-azido carbonyl compounds with phosphines has not been
described in the literature, but at this point, the reaction was not investigated further.
Similarly to the reaction of azide (5) with triphenylphosphine, reduction to 1 was also observed with zinc
in cold hydrochloric acid or in boiling acetic acid. Better results with respect to the synthesis of 4 were
obtained with zinc and acetic acid, when the reactions were conducted at temperatures below 20 °C. Thus,

besides 1 and some unidentified by-products, compounds (4) were formed as major products and were
isolated in 21–68% yields (Scheme 2, Table 1).
Table 1. Synthesis of 3-aminoquinoline-2,4(1H,3H)-diones (4).a
Product
4
reaction timeb, yieldc
R1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
R2
Bu
Bu
Bu
Bu
Bu
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Ph
R3
H
Me
Bu
from 2
24,e 55
24,e 72f
3, 92
from 3
from 5d
4Aa
4Ab
4Ac
4Ad
4Ae
4Ba
4Bb
4Bc
4Bd
4Be
4Ca
4Cb
4Cc
4Cd
4Ce
4Cfg
4Da
4Db
4Dc
4Dd
4De
4Df
4Ea
4Eb
4Ec
4Edg
4Eeg
4Ef
0.5, 51
0.5, 62
0.5, 21
c-C6H11
CH2Ph
H
Me
Bu
c-C6H11
CH2Ph
H
Me
Bu
c-C6H11
CH2Ph
Ph
24,e 81
24,e 86
24,e 62
6, 52f
24,e 83
24,e 51
24,e 53
18, 53
3.5, 63f
24,e 55
24,e 35
24,e 60
144,e 78
24,e 92
3, 87f
24,e 92
H
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
H
Me
Bu
0.5, 68
24,e 90
24,e 68
24,e 61
24,e 76
2, 35
24,e 77
24,e 72
c-C6H11
CH2Ph
Ph
H
Me
Bu
2.5, 70f
24,e 51
5, 86
c-C6H11
CH2Ph
Ph
5, 84
Ph
24,e 59
24,e 30
2, 85f
4Fa
4Fb
4Fc
4Fd
4Fe
4Ff
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
H
Me
Bu
Ph
Ph
Ph
Ph
24,e 59
1.5, 46
1.5, 77
48, 65
c-C6H11
CH2Ph
Ph
Ph
a Reactions conducted at room temperature, unless otherwise indicated. b Reaction time in h.
c Refers to isolated percent yield. d By reduction with zinc in glacial acetic acid. e Non-
optimized. f Methylamine was in situ generated from its HCl salt and K2CO3, see
EXPERIMENTAL. g Isolated as benzene solvate, please see EXPERIMENTAL. h Reaction
continued for 5 h at 60 °C, and then for 4 h at 80 °C.
Having in mind the easiness of the hydrolysis of halo substituted compounds (2) and (3), we turned our

attention back to the ammonolysis. We found out that in contrast to the above discussed approaches, the
highest yields of primary amines (4) (30–92%) can be accessed by reaction of 2 or 3 with ammonia, in
situ generated from ammonium chloride and potassium carbonate in dimethylformamide, under
anhydrous conditions.
In conclusion, we have addressed different approaches for the synthesis of primary and secondary amines
(4).
Scheme 2
O
1
N3
R2
Ph3P
NaN3
2 or 3
N
R1
O
Zn/AcOH
temp. below 20°
4 + 1
5
Table 2. Synthesis of 3-azidoquinoline-2,4(1H,3H)-diones
(5) from 2 or 3 according to Scheme 2.
Starting
X
R1
R2
product 5 yield [a]
compound
2
2
2
2
3
2
2
Cl
Cl
Cl
Cl
Br
Cl
Cl
H
H
H
Me
Me
Ph
Bu
CH2Ph
Ph
Ph
Ph
Me
Ph
5A
5B
5C
5D
5D
5E
5F
96
93
32
93
79
75
63
CH2Ph
a Refers to isolated percent yield.
EXPERIMENTAL
Melting points were determined on a Kofler block or Gallenkamp apparatus and are uncorrected. IR
spectra were recorded on Perkin-Elmer (421 and 1310) and Mattson 3000 spectrophotometers using
samples in potassium bromide disks. NMR spectra were recorded on a Bruker DPX-300 spectrometer in
DMSO-d6 (unless otherwise indicated), with TMS as internal reference. MS spectra were obtained with
VG-Analytical AutospecQ instrument. Column chromatography was carried out on silica gel (Kavalier,
Votice) using benzene and then successive mixtures of benzene-ethyl acetate (in ratios from 99:1 to 8:2)
as eluant (solvent system S). Reactions as well as the course of separation were monitored by TLC on
Silufol UV 254 foils (Kavalier, Votice), using benzene-ethyl acetate (4:1) and chloroform-ethanol (9:1) as
the eluting systems. Elemental analyses (C, H, N) were performed with Perkin-Elmer 2400 CHN
Analyzer and EA 1108 Elemental Analyzer (Fisons Instrument).
Starting 4-hydroxy-2(1H)-quinolones (1) were prepared by known condensation of anilines with

substituted diethyl malonates as described in the literature.3,9 Physical and spectroscopic data of
compounds (1A,18 1B,18,19 1C,19,20 1D,5,19,20 and 1E)5 are published elsewhere.
1-Benzyl-4-hydroxy-3-phenyl-2(1H)-quinolone (1F). Colorless crystals, mp 254–255 °C (butanol),
yield 78%, lit.,21 mp 256–258 °C (acetic acid); IR 3036, 2980, 2953, 1620, 1563, 1497, 1455, 1439, 1330,
1
1310, 1270, 1235, 1170, 1150, 1068, 764, 755, 742, 700 cm–1; H NMR (CDCl3) δ 5.57 (s, 2H, CH2),
6.17 (s, 1H, OH), 7.20-7.34 (m, 7H), 7.40-7.59 (m, 6H), 8.06 (dd, 1H, 5-H, J = 8.0, 1.5 Hz). Anal. Calcd
for C22H17NO2: C, 80.71; H, 5.23; N, 4.28. Found: C, 81.11; H, 5.31; N, 4.28.
General Procedure for the Synthesis of 3-Chloroquinoline-2,4(1H,3H)-diones (2). To a stirred
suspension of 4-hydroxy-2(1H)-quinolone (1) (50 mmol) in dioxane (260 mL) preheated to 50 °C,
sulfuryl chloride (16.2 g, 120 mmol) was added dropwise, keeping the temperature below 55 °C. The
resulting reaction mixture was stirred for additional 10 min at 50–55 °C, cooled down to rt and poured
into ice-water (2 L). The precipitated 3-chloroquinoline-2,4(1H,3H)-dione (2) was filtered and washed
with water.
3-Butyl-3-chloroquinoline-2,4(1H,3H)-dione (2A). Yellow crystals, mp 136–138 °C (benzene), yield
97%; IR 3210, 3147, 3089, 3004, 2941, 2870, 1708, 1688, 1611, 1598, 1485, 1439, 1379, 1373, 1361,
1
1300, 1254, 1156, 1108, 971, 956, 833, 758, 670 cm–1; H NMR δ 0.83 (t, 3H, CH3, J = 7.0 Hz), 1.10-
1.33 (m, 4H, 2- and 3-H of butyl), 2.27 (t, 2H, 1-H of butyl, J = 7.8 Hz), 7.16 (d, 1H, 8-H, J = 7.9 Hz),
7.20 (dt, 1H, 6-H, J = 7.7, 0.6 Hz), 7.69 (dt, 1H, 7-H, J = 7.7, 1.5 Hz), 7.85 (dd, 1H, 5-H, J = 7.8, 1.2 Hz),
11.30 (s, 1H, NH); 13C NMR δ 13.49, 22.11, 26.49, 35.41, 67.00, 116.65, 117.13, 123.31, 127.68, 137.02,
140.95, 166.66, 188.30. Anal. Calcd for C13H14NO2Cl: C, 62.03; H, 5.61; N, 5.56. Found: C, 62.42; H,
5.57; N, 5.44.
3-Benzyl-3-chloroquinoline-2,4(1H,3H)-dione (2B). Yellow crystals, mp 187–189 °C (ethanol), yield
92%, lit.,9 mp 181 °C (water-acetic acid).
3-Chloro-3-phenylquinoline-2,4(1H,3H)-dione (2C). Yellow crystals, mp 178–180 °C (ethanol), yield
89%, lit.,12 mp 181 °C.
3-Chloro-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (2D). Yellow crystals, mp 121–123 °C
(ethanol), yield 98%, lit.,9 mp 154 °C (ethanol).
3-Chloro-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (2E). Yellow crystals, mp 195–197 °C
(ethanol), yield 90%; IR 3101, 3080, 3073, 3059, 3037, 2994, 2940, 1707, 1677, 1595, 1580, 1492, 1482,
1461, 1436, 1372, 1344, 1303, 1255, 1197, 1158, 1133, 1104, 1071, 1052, 962, 893, 806, 771, 762, 740,

700, 666, 646, 606, 553, 535, 515, 445, 432 cm–1; 1H NMR (CDCl3) δ 2.02 (s, 3H, CH3), 6.48 (d, 1H, 8-H,
J = 8.2 Hz), 7.16-7.60 (m, 7H), 8.06 (dd, 1H, 5-H, J = 7.7, 1.6 Hz); EIMS m/z(relative intensity) 287(28),
286(16), 285(67), 252(15), 251(68), 250(99), 249(26), 223(25), 222(100), 221(9), 220(14), 196(29),
195(87), 194(15), 167(47), 166(25), 146(33), 139(17), 92(22), 83(18), 81(17), 78(21), 77(59), 76(16).
Anal. Calcd for C16H12NO2Cl: C, 67.26; H, 4.23; N, 4.90. Found: C, 67.64; H, 4.03; N, 4.98.
1-Benzyl-3-chloro-3-phenylquinoline-2,4(1H,3H)-dione (2F). Yellowish crystals, mp 131–133 °C
(benzene–cyclohexane), yield 74%; IR 3068, 3052, 2931, 1721, 1687, 1601, 1490, 1464, 1451, 1436,
1370, 1360, 1311, 1270, 1212, 1167, 946, 909, 858, 824, 773, 761, 750, 720, 693, 666, 626, 615, 582, 564,
525, 515, 493, 457, 436 cm–1; 1H NMR δ 5.32, 5.39 (2d, each, 1H, CH2, J = 16.7 Hz), 7.19-7.43 (m, 12H,
6-H, 8-H, and phenyl protons), 7.60 (ddd, 1H, 7-H, J = 8.2, 7.5, 1.7 Hz), 7.93 (dd, 1H, 5-H, J = 7.8, 1.7
13
Hz); C NMR δ 46.62, 76.15, 116.38, 120.15, 123.68, 126.43, 127.19, 127.26, 128.02, 128.54, 128.82,
129.45, 134.81, 135.88, 136.51, 140.89, 166.36, 186.99. Anal. Calcd for C22H16NO2Cl: C, 73.03; H, 4.46;
N 3.87. Found: C, 73.38; H, 4.35; N, 3.85.
General Procedure for the Preparation of 3-Bromoquinoline-2,4(1H,3H)-diones (3). To a stirred
suspension of 4-hydroxy-2(1H)-quinolone (1) (20 mmol) in glacial acetic acid (50 mL) at rt, bromine (4.8
g, 30 mmol) was added dropwise during 10 min. The reaction mixture was stirred for 10 min and poured
into ice-water (300 mL). The 3-bromoquinoline-2,4(1H,3H)-dione (3) was filtered out and washed with
water.
3-Bromo-3-butylquinoline-2,4(1H,3H)-dione (3A). Yellow crystals, mp 119–123 °C (hexane), yield
93%, lit.,11 mp 111–113 °C (ethanol).
3-Benzyl-3-bromoquinoline-2,4(1H,3H)-dione (3B). Yellow crystals, mp 181–184 °C (ethanol), yield
97%, lit.,11 mp 156–158 °C (ethanol).
3-Bromo-3-phenylquinoline-2,4(1H,3H)-dione (3C). Yellow crystals, mp 173–175 °C (ethanol), yield
92%, lit.,9 mp 173 °C (ethanol).
3-Bromo-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (3D). Yellow crystals, mp 89–94 °C (ethanol),
yield 97%; IR 3077, 3057, 2987, 2939, 2889, 1710, 1682, 1600, 1489, 1471, 1447, 1416, 1345, 1306,
1
1237, 1172, 1136, 1057, 1039, 960, 900, 801, 775, 750, 700, 680 cm–1; H NMR (CDCl3) δ 3.56 (s, 3H,
CH3), 7.23 (dt, 1H, 6-H, J = 8.4, 1.5 Hz), 7.30-7.50 (m, 6H, 8-H and phenyl protons), 7.67 (dt, 1H, 7-H, J
= 7.9, 1.5 Hz), 8.09 (dd, 1H, 5-H, J = 7.8, 1.5 Hz). Anal. Calcd for C16H12NO2Br: C, 58.20; H, 3.66; N,
4.24. Found: C, 57.54; H, 3.51; N, 4.48.

3-Bromo-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (3E). Yellow crystals, mp 187–190 °C
(benzene), yield 79%; IR 3089, 3063, 3044, 3017, 2938, 1703, 1669, 1599, 1492, 1482, 1460, 1438, 1412,
1373, 1344, 1302, 1264, 1256, 1198, 1163, 1132, 1109, 1099, 1071, 1053, 1040, 1024, 1001, 979, 966,
960, 892, 792, 768, 700, 667, 644, 576, 549, 524, 513, 446, 435, 427 cm–1; 1H NMR δ 2.04 (s, 3H, CH3),
6.37 (d, 1H, 8-H, J = 8.2 Hz), 7.21-7.36 (m, 3H), 7.49-7.64 (m, 4H), 7.99 (dd, 1H, 5-H, J = 7.7, 1.6 Hz);
13C NMR δ 20.02, 55.04, 116.29, 118.85, 123.00, 127.62, 128.38, 128.86, 130.08, 135.43, 137.28, 142.67,
167.55, 187.15. Anal. Calcd for C16H12NO2Br: C, 58.20; H, 3.66; N, 4.24. Found: C, 58.56; H, 3.64; N,
4.17.
1-Benzyl-3-bromo-3-phenylquinoline-2,4(1H,3H)-dione (3F). Yellow crystals, mp 132–135 °C
(benzene–cyclohexane), yield 39%,; IR 3089, 3055, 3029, 2972, 2931, 1698, 1670, 1599, 1497, 1489,
1467, 1454, 1443, 1376, 1360, 1322, 1310, 1257, 1220, 1201, 1167, 1155, 1131, 1077, 1028, 1020, 950,
874, 865, 818, 769, 759, 745, 735, 702, 696, 661, 631, 612, 593, 549, 528, 513, 495, 461, 430, 416 cm–1;
1H NMR (CDCl3) δ 5.23, 5.48 (2d, each, 1H, CH2, J = 16.4 Hz), 7.09 (d, 1H, 8-H, J = 8.4 Hz), 7.17 (ddd,
1H, 6-H, J = 7.6, 7.6, 0.5 Hz), 7.25-7.42 (m, 9H), 7.47-7.53 (m, 3H), 8.10 (dd, 1H, 5-H, J = 7.8, 1.6 Hz);
13C NMR (CDCl3) δ 47.32, 76.61, 116.07, 119.92, 123.93, 126.42, 127.68, 128.57, 128.91, 129.02,
129.20, 129.41, 134.03, 135.49, 136.50, 141.33, 167.65, 187.76. Anal. Calcd for C22H16NO2Br: C, 65.04;
H, 3.97; N, 3.45. Found: C, 65.29; H, 3.81; N, 3.29.
General Procedure for the Reaction of 2 or 3 with Primary Amines. A mixture of 2 or 3 (5 mmol) in
DMF (9 mL) and the appropriate primary amine (15 mmol) was left at rt for the time indicated in Table 1.
The resulting mixture was poured into ice-water (100 mL) and the crude product (4) was separated and
purified, depending on its physical appearance, as follows.
Oily amines (4Dc) and (4De) were extracted with benzene (3 × 30 mL). The combined extracts were
dried over potassium carbonate and evaporated in vacuo. The resulting residue was purified by column
chromatography using solvent system S.
In the case of 4Fc the crude oily product was purified as follows. The crude oily product was dissolved in
methanol (5 mL), acidified with concentrated hydrochloric acid (2 mL) and the resulting mixture was
evaporated to dryness. Thus obtained residue was washed with dry ether (2 × 20 mL) and crystallized
repeatedly from isopropyl alcohol affording 4Fc ⋅ HCl (1.310 g, 60%). The hydrochloride 4Fc ⋅ HCl (870
mg, 2.00 mmol) was then suspended in ether (15 mL) and treated with potassium carbonate (553 mg, 4
mmol) and water (1 mL). After the solid material dissolved, the layers were separated, and aqueous layer
was extracted with ether (4 × 15 mL). The combined organic layers were dried over potassium carbonate
and evaporated in vacuo. From the oily residue the amine (4Fc) (776 mg, 97% from hydrochloride,

overall yield 59%) slowly crystallized out.
Separation and purification of crystalline amines (4Ac–e, 4Bc–e, 4Cc, 4Ce, 4Dd, 4Df, 4Ec–f, and 4Fd-f):
Precipitated crude amine from the above protocol was filtered off and dissolved in a mixture of benzene
(20 mL) and hydrochloric acid (5%, 20 mL). Layers were separated and benzene layer was extracted with
hydrochloric acid (5%, 2 × 10 mL). The collected aqueous layers were made alkaline by the addition of
concentrated aqueous ammonia. Precipitated amine (4) was filtered off, washed with water, and purified
by crystallization from the solvent, as indicated below.
In the case of 4Cd the following workup was necessary to obtain pure product. Precipitated crude amine
from the above protocol was filtered off and shortly boiled (while stirred) in a mixture of benzene (25
mL) and hydrochloric acid (2.5%, 60 mL). Some solid material remained undissolved. The resulting
mixture was cooled down and filtered. The filter cake was crystallized from ethanol and washed with dry
ether affording 4Cd ⋅ HCl (1.15 g, 62%, mp 215–226 °C). A part of thus obtained 4Cd ⋅ HCl (1.00 g) was
suspended in aqueous potassium carbonate (15%, 20 mL) and extracted with a mixture of ether (35 mL)
and chloroform (35 mL). Layers were separated and aqueous layer was extracted with chloroform (3 × 5
mL). The combined organic layers were evaporated to dryness and the residue was crystallized from
benzene to give pure amine (4Cd) (507 mg, 56% from hydrochloride, 35% overall).
3-Butyl-3-butylaminoquinoline-2,4(1H,3H)-dione (4Ac). Colorless crystals, mp 134–136 °C (benzene);
IR 3295, 3064, 3047, 2957, 2927, 2854, 1719, 1703, 1676, 1612, 1486, 1441, 1356, 1298, 1246, 1184,
935, 883, 830, 751 cm–1; 1H NMR δ 0.75 (t, 3H, CH3 of C-butyl, J = 6.7 Hz), 0.82 (t, 3H, CH3 of N-butyl,
J = 7.1 Hz), 1.05-1.38 (m, 8H), 1.65-1.81 (m, 2H, 1-H of C-butyl), 2.20-2.28 (m, 3H, 3-NH and 1-H of
N-butyl), 7.10 (d, 1H, 8-H, J = 7.8 Hz), 7.12 (d, 1H, 6-H, J = 7.8 Hz), 7.61 (dt, 1H, 7-H, J = 7.8, 1.5 Hz),
13
7.77 (dd, 1H, 5-H, J = 8.2, 1.5 Hz), 10.93 (s, 1H, 1-H); C NMR δ 13.56, 13.69, 19.66, 22.11, 24.96,
32.07, 44.00, 72.89, 116.27, 119.13, 122.55, 126.53, 136.21, 141.57, 172.82, 196.44. Anal. Calcd for
C17H24N2O2: C, 70.80; H, 8.39; N 9.71. Found: C, 71.19; H, 8.44; N, 9.67.
3-Butyl-3-cyclohexylaminoquinoline-2,4(1H,3H)-dione (4Ad). Colorless crystals, mp 190–194 °C
(benzene–cyclohexane); IR 3331, 3186, 3065, 2926, 2854, 1706, 1692, 1668, 1609, 1596, 1484, 1372,
1357, 1291, 1230, 1160, 946, 888, 800, 757, 666 cm–1; 1H NMR δ 0.73 (t, 3H, CH3 of butyl, J = 7.0 Hz),
0.85-1.60 (m, 14H), 1.65-1.76 (m, 2H), 2.22 (br s, 1H, 3-NH), 2.38-2.48 (m, 1H), 7.08-7.16 (m, 2H, 6-
and 8-H), 7.61 (dt, 1H, 7-H, J = 7.7, 1.5 Hz), 7.80 (dd, 1H, 5-H, J = 8.1, 1.5 Hz), 10.95 (s, 1H, 1-H); 13C
NMR δ 13.51, 22.13, 24.60, 24.72, 25.31, 33.85, 34.39, 41.16, 52.83, 70.55, 116.35, 118.80, 122.61,
126.62, 136.26, 141.60, 173.27, 196.76. Anal. Calcd for C19H26N2O2: C, 72.58; H, 8.33; N, 8.91. Found:
C, 72.35; H, 8.14; N, 9.11.

3-Benzylamino-3-butylquinoline-2,4-(1H,3H)-dione (4Ae). Colorless crystals, mp 130–132 °C
(cyclohexane); IR 3060, 2859, 2754, 1710, 1699, 1674, 1612, 1488, 1459, 1444, 1365, 1297, 1249, 1217,
1
1175, 1105, 979, 937, 838, 802, 757, 751, 704, 659 cm–1; H NMR δ 0.76 (t, 3H, CH3 of butyl, J = 7.0
Hz), 1.09-1.23 (m, 4H, 2- and 3-H of butyl), 1.70-1.88 (m, 2H, 1-H of butyl), 2.67 (br s, 1H, 3-NH), 3.47,
3.53 (2d, each, 1H, PhCH2, J = 12.4 Hz), 7.08-7.36 (m, 7H, 6-H, 8-H, and phenyl protons), 7.62 (dt, 1H,
13
7-H, J = 7.7, 1.5 Hz), 7.78 (dd, 1H, 5-H, J = 8.1, 1.5 Hz), 10.97 (s, 1H, 1-H); C NMR δ 13.58, 22.06,
24.96, 48.51, 73.35, 116.26, 119.19, 122.55, 126.61, 127.91, 128.00, 136.16, 140.39, 141.53, 172.58,
196.09. Anal. Calcd for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69. Found: C, 74.56; H, 6.70; N, 8.92.
3-Benzyl-3-butylaminoquinoline-2,4-(1H,3H)-dione (4Bc). Colorless crystals, mp 163–166 °C
(benzene); IR 3314, 3226, 3191, 3067, 2959, 2924, 1703, 1688, 1665, 1611, 1593, 1484, 1439, 1371,
1288, 1234, 1160, 940, 764, 701 cm–1; 1H NMR δ 0.81 (t, 3H, CH3, J = 7.1 Hz), 1.17-1.40 (m, 4H, 2- and
3-H of butyl), 2.18-2.42 (m, 3H, 1-H of butyl and 3-NH), 3.06, 3.11 (2d, each, 1H, CH2Ph, J = 13.3 Hz),
6.90 (d, 1H, 8-H, J = 8.0 Hz), 6.93-6.98 (m, 2H, 3- and 5-H of phenyl), 7.02 (dt, 1H, 6-H, J = 7.6, 0.5 Hz),
7.06-7.13 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.47 (dt, 1H, 7-H, J = 7.7, 1.4 Hz), 7.68 (dd, 1H, 5-H, J =
13
7.8, 1.3 Hz), 10.88 (s, 1H, 1-H); C NMR δ 13.66, 19.61, 32.00, 43.81, 45.49, 73.45, 116.06, 119.37,
122.41, 126.23, 126.74, 127.66, 129.82, 133.86, 136.11, 141.38, 172.04, 196.25. Anal. Calcd for
C20H22N2O2: C, 74.51; H, 6.88; N, 8.69. Found: C, 74.58; H, 6.96; N, 8.30.
3-Benzyl-3-cyclohexylaminoquinoline-2,4-(1H,3H)-dione (4Bd). Colorless crystals, mp 197–200 °C
(benzene); IR 3325, 3229, 3064, 2923, 2853, 1702, 1687, 1666, 1609, 1594, 1484, 1366, 1289, 1159, 761,
1
700, 666 cm–1; H NMR δ 0.85-1.10 (m, 6H), 1.39-1.62 (m, 5H), 2.43 (br s, 1H, 3-NH), 3.06 (s, 2H,
CH2Ph), 6.84 (d, 1H, 8-H, J = 7.8 Hz), 6.88-6.95 (m, 2H, 3- and 5-H of phenyl), 6.99 (dt, 1H, 6-H, J = 7.8,
0.8 Hz), 7.01-7.09 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.43 (ddd, 1H, 7-H, J = 7.5, 7.4, 1.5 Hz), 7.68 (dd,
1H, 5-H, J = 7.9, 1.5 Hz), 10.84 (s, 1H, 1-H); 13C NMR δ 24.53, 25.27, 33.87, 34.40, 47.46, 52.76, 71.44,
115.99, 119.08, 122.37, 126.25, 126.77, 127.59, 129.77, 133.47, 136.05, 141.28, 172.51, 196.72. Anal.
Calcd for C22H24N2O2: C, 75.83; H, 6.94; N, 8.04. Found: C, 76.09; H, 6.86; N, 8.36.
3-Benzyl-3-benzylaminoquinoline-2,4-(1H,3H)-dione (4Be). Colorless crystals, mp 192–195 °C
(benzene–ethyl acetate); IR 3300, 3223, 3184, 3063, 3027, 2921, 1703, 1688, 1665, 1644, 1609, 1593,
1483, 1371, 1292, 1232, 1159, 1109, 1082, 1031, 941, 917, 761, 748, 701, 667 cm–1; 1H NMR δ 2.80 (br
s, 1H, 3-NH), 3.15 (t, 2H, NCH2Ph, J = 13.4 Hz), 3.46, 3.54 (each d, each, 1H, CCH2Ph, J = 12.5 Hz),
6.93 (d, 1H, 8-H, J = 8.0 Hz), 6.97-7.01 (m, 2H, 3- and 5-H of phenyl), 7.04 (dt, 1H, 6-H, J = 7.5, 0.7 Hz),
7.08-7.14 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.18-7.34 (m, 5H, phenyl protons), 7.50 (dt, 1H, 7-H, J =
13
7.8, 1.4 Hz), 7.69 (dd, 1H, 5-H, J = 7.8, 1.4 Hz), 10.95 (s, 1H, 1-H); C NMR δ 45.72, 48.30, 116.09,

119.48, 122.43, 126.33, 126.66, 126.83, 127.64, 127.91, 127.94, 129.93, 133.71, 136.09, 140.10, 141.38,
171.75, 195.84. Anal. Calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C, 77.64; H, 5.37; N,
7.59.
3-Butylamino-3-phenylquinoline-2,4-(1H,3H)-dione (4Cc). Colorless crystals, mp 123–126 °C
(benzene–cyclohexane); IR 3300, 3068, 3052, 3035, 2965, 2924, 2905, 2851, 1716, 1701, 1672, 1614,
1594, 1487, 1446, 1358, 1344, 1317, 1249, 1231, 903, 758. 740, 695, 590, 514, 438 cm–1; 1H NMR δ 0.85
(t, 3H, CH3, J = 7.2 Hz), 1.25-1.48 (m, 4H, 2- and 3-H of butyl), 2.36-2.45 (m, 2H, NCH2), 2.61 (s, 1H, 3-
NH), 7.06-7.14 (m, 2H), 7.27-7.36 (m, 3H), 7.36-7.41 (m, 2H), 7.60 (ddd, 1H, 7-H, J = 8.44, 6.98, 1.46
13
Hz), 7.71 (dd, 1H, 5-H, J = 7.70, 1.29 Hz), 11.23 (s, 1H, 1-H); C NMR δ 13.72, 19.71, 32.12, 44.34,
76.47, 116.38, 119.05, 122.84, 126.41, 127.10, 128.38, 128.62, 136.33, 137.92, 141.14, 171.65, 193.89.
Anal. Calcd for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08. Found: C, 73.61; H, 6.33; N, 9.17.
3-Cyclohexylamino-3-phenylquinoline-2,4-(1H,3H)-dione (4Cd). Colorless crystals, mp 184–188 °C
(benzene); IR 3306, 3047, 2975, 2929, 2854, 2757, 2735, 2689, 2668, 1709, 1692, 1669, 1611, 1594,
1507, 1487, 1466, 1444, 1359, 1353, 1324, 1314, 1252, 1230, 1196, 1161, 1135, 1109, 1083, 1053, 1036,
986, 958, 938, 905, 888, 848, 809, 787, 759, 744, 697, 662, 618, 608, 596, 546, 528, 523, 513, 470, 439,
429 cm–1; 1H NMR δ 0.96-1.17 (m, 5H), 1.40-1.66 (m, 5H), 2.58 (br s, 2H), 7.11 (ddd, 1H, 6-H, J = 7.6,
7.6, 0.8 Hz), 7.16 (d, 1H, 8-H, J = 8.1 Hz), 7.23-7.33 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.36-7.44 (m, 2H,
3- and 5-H of phenyl), 7.62 (ddd, 1H, 7-H, J = 8.2, 7.2, 1.5 Hz), 7.74 (dd, 1H, 5-H, J = 7.8, 1.3 Hz), 11.24
(s, 1H, 1-H); 13C NMR δ 24.82, 25.33, 34.24, 34.61, 53.08, 74.54, 116.49, 118.51, 122.93, 126.30, 127.30,
128.26, 128.54, 136.43, 138.97, 141.22, 172.34, 194.07. Anal. Calcd for C21H22N2O2: C, 75.42; H, 6.63;
N, 8.38. Found: C, 75.69; H, 6.53; N, 8.61.
3-Cyclohexylamino-3-phenylquinoline-2,4(1H,3H)-dione hydrochloride (4Cd ⋅ HCl). Colorless
crystals, mp 209–213 °C (ethanol); IR 3300-3700 (br), 3181, 3087, 3054, 3033, 2981, 2938, 2922, 2903,
2857, 1725, 1677, 1611, 1592, 1560, 1503, 1497, 1484, 1454, 1431, 1423, 1384, 1367, 1358, 1327, 1299,
1247, 1229, 1150, 1122, 1091, 1034, 1024, 980, 956, 893, 874, 868, 786, 775, 764, 747, 709, 699, 683,
667, 589, 549, 540, 525, 501, 472, 456, 439 cm–1; 1H NMR δ 0.99-1.18 (m, 3H), 1.38-1.54 (m, 3H), 1.65-
1.82 (m, 4H), 3.45 (dd, 1H, NCH, J = 14.0, 7.0 Hz), 7.20 (ddd, 1H, 6-H, J = 7.5, 7.5 and 0.5 Hz), 7.32 (d,
1H, 8-H, J = 8.1 Hz), 7.51 (s, 5H, phenyl protons), 7.67 (ddd, 1H, 7-H, J = 7.9, 7.6 and 1.4 Hz), 7.86 (dd,
1H, 5-H, J = 7.8 and 1.0 Hz), 9.98 (s, 2H, NH+2 ), 12.18 (s 1H, 1-H). 13C NMR 24.51, 30.44, 30.76, 57.73,
74.44, 117.04, 117.94, 123.84, 127.55, 128.21, 129.56, 130.97, 137.44, 140.52.
3-Benzylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Ce). Colorless crystals, mp 178–179 °C

(benzene); IR 3312, 3224, 3161, 3096, 3065, 3026, 3001, 2931, 2900, 2867, 2849, 1710, 1699, 1667,
1613, 1593, 1508, 1485, 1441, 1361, 1322, 1270, 1255, 1238, 1225, 1178, 1157, 1110, 1080, 1069, 1034,
1029, 1015, 979, 966, 947, 908, 868, 815, 771, 760, 740, 704, 693, 670, 662, 601, 583, 532, 527, 497, 488,
446, 441 cm–1; 1H NMR δ 3.01 (dd, 1H, 3-NH, J = 7.9, 6.5 Hz), 3.58-3.70 (m, 2H, CH2), 7.10 (ddd, 1H,
6-H, J = 7.6, 7.6, 0.6 Hz), 7.15 (d, 1H, 8-H, J = 8.0 Hz), 7.20-7.50 (m, 10H, phenyl protons), 7.60 (ddd,
1H, 7-H, J = 9.0, 7.9, 1.5 Hz), 7.74 (dd, 1H, 5-H, J = 7.8, 1.3 Hz), 11.29 (s, 1H, 1-H). 13C NMR δ 48.79,
76.62, 116.40, 119.22, 122.86, 126.53, 126.65, 127.14, 127.97, 127.99, 128.57, 128.75, 136.31, 137.55,
140.49, 141.11, 171.43, 193.74. Anal. Calcd for C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C, 77.47;
H, 5.09; N, 8.40.
3-Phenyl-3-phenylaminoquinoline-2,4(1H,3H)-dione benzene solvate (4Cf ⋅ ½C6H6). Yellow crystals,
mp 139–150 °C (benzene); IR 3383, 3193, 3119, 3066, 2993, 2927, 2872, 2756, 1708, 1667, 1615, 1601,
1502, 1484, 1449, 1437, 1365, 1341, 1312, 1257, 1252, 1231, 1179, 1158, 1109, 1082, 1036, 1021, 1003,
993, 970, 956, 923, 882, 868, 838, 813, 777, 762, 744, 723, 694, 663, 625, 617, 548, 522, 505, 475, 441,
420 cm–1; 1H NMR δ 6.33 (d, 2H, 2- and 6-H of N-phenyl, J = 7.7 Hz), 6.55 (dd, 1H, 4-H of N-phenyl, J
= 7.3, 7.3 Hz), 6.69 (s, 1H, 3-NH), 7.01 (dd, 2H, 3- and 5-H of N-phenyl, J = 8.2, 7.5 Hz), 7.12 (ddd, 1H,
6-H, J = 7.5, 7.5, 0.6 Hz), 7.19 (d, 1H, 8-H, J = 7.9 Hz), 7.35-7.44 (m, 6H, 2-, 4-, and 6-H of 3-phenyl
and ½C6H6), 7.45-7.52 (m, 2H, 3- and 5-H of 3-phenyl), 7.63 (ddd, 1H, 7-H, J = 8.2, 7.2, 1.5 Hz), 7.76
13
(dd, 1H, 5-H, J = 7.8, 1.4 Hz), 11.40 (s, 1H, 1-H); C NMR δ 74.48, 113.73, 116.51, 116.59, 119.14,
122.96, 127.20, 127.40, 128.21 (C6H6), 128.40, 128.95, 129.13, 135.54, 136.50, 140.86, 146.05, 170.53,
192.96. Anal. Calcd for C21H16N2O2 ⋅ ½C6H6: C, 78.45; H, 5.21; N, 7.62. Found: C, 78.80; H, 5.03; N,
7.77.
3-Phenyl-3-phenylaminoquinoline-2,4(1H,3H)-dione ethanol solvate (4Cf ⋅ EtOH). The compound
(4Cf ⋅ ½C6H6) (170 mg, 0.463 mmol) was dissolved in ethanol (2 mL), the solution was acidified with
concentrated hydrochloric acid (0.2 mL), and evaporated to dryness. The residue was washed with dry
ether (2 mL) and crystallized from ethanol to give yellow crystals, 148.4 mg (86%), mp 125-129 °C; IR
3465 (br), 3331, 3216, 3182, 3149, 3083, 3049, 2972, 2911, 2863, 2753, 1707, 1671, 1601, 1499, 1484,
1449, 1431, 1356, 1313, 1282, 1256, 1227, 1185, 1163, 1110, 1081, 1037, 1002, 993, 964, 925, 908, 901,
881, 871, 843, 834, 814, 789, 768, 749, 742, 722, 699, 682, 668, 661, 616, 534, 509, 490, 436, 415 cm–1;
1H NMR 1.06 (t, 3H, CH3, J = 7.0 Hz), 3.40-3.49 (m, 2H, CH2), 4.34 (t, 1H, OH, J = 5.1 Hz), 6.32 (d, 2H,
2- and 6-H of N-phenyl, J = 7.8 Hz), 6.55 (dd, 1H, 4-H of N-phenyl, J = 7.3, 7.3 Hz), 6.68 (s, 1H, 3-NH),
7.01 (dd, 2H, 3- and 5-H of N-phenyl, J = 8.3, 7.5 Hz), 7.12 (ddd, 1H, 6-H, J = 7.5, 7.5, 0.9 Hz), 7.19 (d,
1H, 8-H, J = 8.0 Hz), 7.36-7.45 (m, 3H, 2-, 4-, and 6-H of 3-phenyl), 7.47-7.50 (m, 2H, 3- and 5-H of 3-

phenyl), 7.64 (ddd, 1H, H-7, J = 8.0, 7.5, 1.5 Hz), 7.75 (dd, 1H, H-5, J = 7.8, 1.4 Hz), 11.40 (s, 1H, 1-H);
13C NMR 18.46, 55.95, 74.47, 113.73, 116.51, 116.59, 119.14, 122.96, 127.20, 127.40, 128.41, 128.96,
129.14, 135.54, 136.51, 140.86, 146.05, 170.53, 192.97. Anal. Calcd for C21H16N2O2 ⋅ C2H6O: C, 73.78;
H, 5.92; N, 7.48. Found: C, 74.15; H, 6.18; N, 7.40.
3-Butylamino-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (4Dc). Yellow oil; IR 3328, 3060, 2955,
2928, 2858, 1704, 1666, 1602, 1492, 1470, 1447, 1352, 1303, 1186, 1122, 1112, 1033, 997, 762, 698
cm-1; 1H NMR δ 0.85 (t, 3H, CH3 of butyl, J = 7.2 Hz), 1.23-1.37 (m, 2H, 3-H of butyl), 1.37-1.51 (m, 2H,
2-H of butyl), 2.30-2.53 (m, 2H, 1-H of butyl), 2.66 (br s, 1H, NH), 3.53 (s, 1H, NCH3), 7.17 (t, J = 7.4
Hz, 1H, 6-H), 7.23-7.33 (m, 5H, phenyl protons), 7.38 (d, 1H, 8-H, J = 8.3 Hz), 7.69 (dt, 1H, 7-H, J = 7.8,
1.5 Hz), 7.76 (dd, 1H, 5-H, J = 7.7, 1.5 Hz); 13C NMR δ 13.71, 19.70, 29.84, 32.14, 44.31, 77.05, 115.80,
120.56, 123.12, 126.52, 127.28, 128.45, 128.62, 136.23, 137.84, 142.12, 171.15, 192.79. HRMS Calcd
for C20H22N2O2: 322.1681. Found: 322.1691.
3-Cyclohexylamino-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (4Dd). Colorless crystals, mp 98–
100 °C (hexane); IR 3333, 2959, 2927, 2851, 1702, 1670, 1603, 1490, 1472, 1443, 1355, 1307, 1123,
1
1113, 1097, 1041, 765, 751, 722, 703, 648 cm–1; H NMR (CDCl3) δ 1.05-1.25 (m, 6H), 1.45-1.70 (m,
4H), 1.82 (br s, 1H, NH), 2.59-2.72 (m, 1H), 3.57 (s, 3H, CH3), 7.11-7.17 (m, 2H, 6- and 8-H), 7.21-7.28
(m, 3H, 2-, 4-, and 6-H of phenyl), 7.34-7.41 (m, 2H, 3- and 5-H of phenyl), 7.58 (dt, 1H, 7-H, J = 7.8,
1.7 Hz), 7.98 (dd, 1H, 5-H, J = 7.9, 1.7 Hz). Anal. Calcd for C22H24N2O2: C, 75.83; H, 6.94; N, 8.04.
Found: C, 76.10; H, 6.86; N, 8.17.
3-Benzylamino-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (4De). Yellow oil; IR 3416, 3340, 3059,
1
3026, 2920, 2850, 1704, 1665, 1601, 1492, 1471, 1352, 1302, 1126, 1109, 1029,783, 761, 698 cm-1; H
NMR δ 3.54 (s, 3H, NCH3), 3.58, 3.71 (each d, each, 1H, PhCH2, J = 12.6 Hz), 7.18 (dt, 1H, 6-H, J = 7.5,
0.5 Hz), 7.24 (d, 1H, 8-H, J = 7.2 Hz), 7.27-7.44 (m, 10H, phenyl protons), 7.69 (dt, 1H, 7-H, J = 7.8, 1.6
Hz), 7.79 (dd, 1H, 5-H, J = 7.7, 1.6 Hz); 13C NMR δ 29.96, 48.83, 77.05, 115.83, 120.73, 123.21, 126.62,
126.67, 127.34, 128.01, 128.03, 128.69, 128.80, 136.29, 137.56, 140.50, 142.14, 171.02, 192.78. HRMS
Calcd for C23H20N2O2: 356.1525. Found: 356.1540.
1-Methyl-3-phenyl-3-phenylaminoquinoline-2,4(1H,3H)-dione (4Df). Colorless crystals, mp 178–
181 °C (ethanol); IR 3415, 3048, 3027, 2932, 1708, 1674, 1599, 1499, 1470, 1447, 1350, 1314, 1302,
1
1262, 1183, 1123, 1115, 1105, 762, 754, 744, 696 cm–1; H NMR δ 3.56 (s, 3H, NCH3), 6.30 (d, 2H, 2-
and 6-H of N-phenyl, J = 7.7 Hz), 6.54 (t, 1H, 4-H of N-phenyl, J = 7.3 Hz), 6.70 (s, 1H, NH), 6.99 (t, 2H,
3- and 5-H of N-phenyl, J = 7.5 Hz), 7.21 (dt, 1H, 6-H, J = 7.5, 0.5 Hz), 7.33-7.42 (m, 5H, 3-phenyl

protons), 7.46 (d, 1H, 8-H, J = 8.3 Hz), 7.74 (dt, 1H, 7-H, J = 7.8, 1.6 Hz), 7.82 (dd, 1H, 5-H, J = 7.7, 1.6
13
Hz); C NMR δ 30.17, 74.80, 113.98, 116.12, 116.50, 120.37, 123.33, 127.21, 127.71, 128.35, 128.97,
129.18, 135.63, 136.57, 142.00, 145.93, 170.03, 191.87. Anal. Calcd for C22H18N2O2: C, 77.17; H, 5.30;
N, 8.18. Found: C, 76.93; H, 5.17; N, 8.20.
3-Butylamino-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (4Ec). Colorless crystals, mp 79–80.5 °C
(cyclohexane); IR 3306, 3076, 3059, 2960, 2922, 2870, 2835, 1692, 1659, 1597, 1491, 1457, 1360, 1334,
1298, 1271, 1249, 1192, 1182, 1168, 1161, 1128, 981, 799, 767, 762, 720, 700, 681, 660, 653, 531, 513,
468, 431 cm–1; 1H NMR δ 0.83 (t, 3H, CH3 of butyl, J = 7.1 Hz), 1.21-1.40 (m, 4H), 1.49 (s, 3H, NCH3),
2.38-2.41 (m, 3H), 6.34 (d, 1H, 8-H, J = 8.3 Hz), 7.19 (dd, 1H, 7-H, J = 7.5, 7.5 Hz), 7.28-7.44 (m, 2H),
7.45-7.57 (m, 2H), 7.57-7.67 (m, 2H), 7.91 (dd, 1H, 5-H, J = 7.7, 1.4 Hz); 13C NMR δ 13.71, 19.70, 24.62,
32.08, 43.76, 69.67, 116.34, 119.60, 122.84, 127.21, 128.67, 129.10, 130.06, 135.61, 137.51, 143.52,
172.55, 194.97. Anal. Calcd for C20H22N2O2: C, 74.51; H, 6.88; N, 8.69. Found: C, 74.29; H, 6.95; N,
8.61.
1
3-Cyclohexylamino-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione benzene solvate (4Ed ⋅ ⁄3C6H6).
Colorless crystals, mp 125–131 °C (benzene); IR 3343, 3323, 3092, 3074, 3056, 3043, 2995, 2976, 2933,
2907, 2849, 2656, 1703, 1666, 1596, 1582, 1491, 1483, 1459, 1438, 1415, 1363, 1331, 1299, 1274, 1264,
1244, 1206, 1190, 1177, 1158, 1122, 1114, 1106, 1068, 1051, 1042, 1023, 1001, 987, 973, 961, 950, 932,
916, 888, 867, 848, 818, 796, 784, 772, 758, 737, 714, 694, 679, 667, 656, 617, 593, 583, 558, 537, 522,
498, 484, 467, 451, 431 cm–1; 1H NMR δ 0.92-1.13 (m, 6H), 1.42-1.49 (m, 1H), 1.47 (s, 3H, CH3), 1.56-
1.66 (m, 4H), 2.39 (s, 1H, NH), 6.35 (d, 2H, 8-H, J = 8.4 Hz), 7.20 (dd, 1H, J = 7.5, 7.5 Hz), 7.20-7.30 (m,
1H), 7.30-7.40 (m, 1H), 7.36 (s, 2H, 1/3C6H6), 7.49-7.56 (m, 2H), 7.59-7.65 (m, 2H), 7.95 (d, 1H, 5-H, J =
13
7.6 Hz); C NMR δ 24.72, 25.32, 25.89, 34.05, 34.56, 52.65, 67.80, 116.41, 119.07, 122.96, 127.46,
128.22 (C6H6), 128.70, 129.18, 130.15, 135,78, 137.46, 143.52, 173.10, 195.17. Anal. Calcd for
C22H24N2O2 ⋅ 1⁄3C6H6: C, 76.98; H, 7.00; N, 7.48. Found: C, 77.19; H, 7.08; N, 7.62.
3-Benzylamino-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione benzene solvate (4Ee ⋅ ¼C6H6).
Colorless crystals, mp 115.5–117 °C (benzene); IR 3322, 3061, 3030, 2984, 2930, 2888, 2839, 1709,
1672, 1601, 1584, 1491, 1462, 1452, 1368, 1334, 1313, 1303, 1276, 1250, 1221, 1208, 1196, 1178, 1159,
1128, 1112, 1071, 1046, 1025, 1003, 979, 907, 896, 866, 830, 818, 784, 766, 755, 726, 701, 675, 658, 597,
540, 524, 511, 464, 446 cm–1; 1H NMR δ 1.58 (s, 3H, CH3), 2.91 (s, 1H, NH), 3.63 (s, 2H, CH2), 6.35 (d,
13
1H, 8-H, J = 8.3 Hz), 7.17-7.41 (m, 9H), 7.48-7.63 (m, 4H), 7.93 (dd, 1H, 5-H, J = 7.7, 1.3 Hz); C
NMR δ 25.11, 48.34, 70.04, 116.37, 119.71, 122.86, 126.56, 127.23, 127.90, 128.09, 128.21 (C6H6),
128.68, 129.13, 130.03, 135.60, 137.53, 140,52, 143.53, 172.46, 194.93. Anal. Calcd for

C23H20N2O2 ⋅ ¼C6H6: C, 78.27; H, 5.76; N, 7.45. Found: C, 78.50; H, 5.37; N, 7.21.
3-Methyl-1-phenyl-3-phenylaminoquinoline-2,4(1H,3H)-dione (4Ef). Colorless crystals, mp 212–
215 °C (ethanol); IR 3357, 3109, 3092, 3063, 3051, 3026, 2980, 2967, 2950, 2926, 2863, 1708, 1661,
1599, 1523, 1499, 1492, 1462, 1435, 1371, 1338, 1315, 1296, 1282, 1255, 1206, 1180, 1161, 1130, 1110,
1071, 1048, 1032, 1002, 993, 987, 955, 898, 864, 841, 817, 809, 782, 768, 752, 743, 714, 696, 683, 662,
618, 560, 533, 524, 516, 438, 427 cm–1; 1H NMR δ 1.72 (s, 3H, CH3), 6.25 (d, 2H, 8-H, J = 8.0 Hz), 6.46
(d, 1H, J = 8.4 Hz), 6.53 (dd, 1H, 6-H, J = 7.3, 7.3 Hz), 6.69 (s, 1H, NH), 7.00-7.06 (m, 2H), 7.23-7.32
(m, 2H), 7.44-7.66 (m, 5H), 7.98 (dd, 1H, 5-H, J = 7.7, 1.2 Hz); 13C NMR δ 25.96, 67.30, 112.98, 116.24,
116.84, 119.04, 123.26, 127.72, 128.68, 128.86, 129.20, 130.12, 136.30, 137.22, 143.43, 145.58, 171.91,
194.57. Anal. Calcd for C22H18N2O2: C, 77.18; H, 5.30; N, 8.18). Found: C, 76.89; H, 5.42; N, 7.73.
1-Benzyl-3-butylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Fc). Colorless crystals, mp 80–84 °C
(hexane); IR 3150-3600 (br), 3331, 3060, 3027, 2952, 2927, 2867, 2853, 1709, 1659, 1601, 1488, 1444,
1377, 1376, 1316, 1222, 1180, 1159, 1118, 1054, 1026, 985, 892, 765, 732, 719, 698, 658, 620, 540, 469,
440 cm–1; 1H NMR (CDCl3) δ 0.90 (t, 3H, CH3, J = 7.3 Hz), 1.30-1.44 (m, 2H), 1.47-1.64 (m, 2H), 2.37
(br, 1H, NH), 2.48-2.56, 2.63-2.71 (2m, each, 1H, 1-H of butyl), 5.24, 5.49 (2d, each, CH2 of benzyl, J =
16.3 Hz), 7.00 (d, 1H, 8-H, J = 8.4 Hz), 7.07 (ddd, 1H, 6-H, J = 7.5, 7.5, 0.7 Hz), 7.17-7.44 (m, 11H),
13
8.00 (dd, 1H, 5-H, J = 7.7, 1.6 Hz); C NMR (CDCl3) δ 13.97, 20.40, 32.79, 45.59, 46.85, 115.75,
121.98, 123.44, 126.61, 127.15, 127.52, 128.46, 128.87, 128.94, 135.80, 135.86, 137.22, 141.81, 172.18,
193.65. Anal. Calcd for C26H26N2O2: C, 78.37; H, 6.58; N, 7.03. Found: C, 78.71; H, 6.59; N, 6.71.
1-Benzyl-3-butylamino-3-phenylquinoline-2,4(1H,3H)-dione hydrochloride (4Fc ⋅ HCl). Colorless
crystals, mp 187–192 °C (isopropyl alcohol); IR 3220-3670 (br), 3062, 3021, 2999, 2967, 2933, 2875,
1710, 1678, 1598, 1570, 1493, 1489, 1468, 1453, 1450, 1437, 1371, 1347, 1335, 1319, 1298, 1279, 1250,
1238, 1218, 1201, 1169, 1145, 1091, 1078, 1060, 1038, 1031, 1018, 979, 962, 936, 905, 841, 772, 752,
737, 717, 703, 658, 607, 589, 533, 521, 508, 447, 439; 1H NMR δ 0.88 (t, 3H, CH3, J = 7.2 Hz), 1.34 (tq,
2H, 3-H of butyl, J = 7.3, 7.3 Hz), 1.76 (tt, 2H, 2-H of butyl, J = 7.2, 7.2 Hz), 2.94-3.16 (m, 2H, 1-H of
butyl), 5.34, 5.44 (2d, each, 1H, CH2Ph, J = 16.6 Hz), 7.23-7.35 (m, 7H), 7.35-7.43 (m, 2H), 7.43-7.55 (m,
3H), 7.62 (dd, 1H, 7-H, J = 7.7, 7.4 Hz), 7.96 (d, 1H, 5-H, J = 7.4 Hz), 10.32 (br s, 2H, NH2); 13C NMR δ
13.36, 19.34, 28.27, 45.93, 46.32, 75.69, 116.72, 120.45, 124.25, 126.73, 127.33, 127.72, 128.28, 128.48,
129.54, 131.15, 135.40, 137.11, 140.52, 165.63, 187.82. Anal. Calcd for C26H26N2O2 ⋅ HCl: C, 71.80; H,
6.26; N, 6.44. Found: C, 71.95; H, 6.21; N, 6.61.
1-Benzyl-3-cyclohexylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Fd). Colorless crystals, mp 134–

137 °C (cyclohexane); IR 3300-3600 (br), 3340, 3085, 3051, 3035, 3001, 2969, 2928, 2917, 2844, 1703,
1669, 1599, 1495, 1488, 1465, 1450, 1428, 1373, 1362, 1309, 1301, 1269, 1254, 1244, 1214, 1197, 1174,
1162, 1106, 1081, 1069, 1058, 1036, 1030, 1007, 964, 941, 933, 916, 903, 883, 856, 847, 797, 777, 762,
1
751, 738, 706, 697, 664, 617, 586, 550, 527, 519, 512, 482, 462, 432, 418, 412 cm–1; H NMR δ 0.95-
1.18 (m, 5H), 1.41-1.71 (m, 5H), 2.61 (s, 1H, NH), 2.71 (s, 1H, H-1 of cyclohexyl), 5.31, 5.55 (2d, each,
1H, NCH2, J = 16.4 Hz), 7.17 (dd, 1H, 6-H, J = 7.2, 7.7 Hz), 7.22-7.41 (m, 11H, 8-H and phenyl protons),
7.60 (ddd, 1H, 7-H, J = 8.5, 7.2, 1.5 Hz), 7.86 (dd, 1H, J = 7.7, 1.5 Hz); 13C NMR δ 24.90, 25.32, 34.46,
34.70, 45.41, 53.24, 75.23, 116.41, 120.35, 123.46, 126.57, 126.64, 127.22, 127.89, 128.49, 128.55,
128.60, 136.21, 136.39, 138.61, 141.23, 172.18, 193.22. Anal. Calcd for C28H28N2O2: C, 79.22; H, 6.65;
N, 6.60. Found: C, 79.46; H, 6.59; N, 6.76.
1-Benzyl-3-benzylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Fe). Colorless crystals, mp 120–
122 °C (cyclohexane); IR 3200-3600 (br), 3317, 3085, 3060, 3026, 3005, 2958, 2921, 2906, 2844, 2807,
1705, 1672, 1598, 1586, 1559, 1540, 1495, 1486, 1466, 1458, 1443, 1364, 1355, 1339, 1322, 1315, 1304,
1263, 1231, 1207, 1200, 1174, 1158, 1116, 1083, 1064, 1047, 1031, 1017, 999, 970, 951, 931, 906, 882,
858, 845, 777, 759, 748, 732, 720, 702, 669, 662, 623, 616, 596, 571, 531, 517, 508, 488, 456, 439, 419
cm–1; 1H NMR δ 3.08-3.14 (m, 1H, NH), 3.64 (dd, 1H, NCH, J = 12.5, 5.4 Hz), 3.75 (dd, 1H, NCH, J =
12.4, 8.7 Hz), 5.42 (s, 2H, CH2), 7.15 (dd, 1H, 6-H, J = 7.5, 7.5 Hz), 7.20-7.44 (m, 16H, 8-H and phenyl
protons), 7.57 (ddd, 1H, 7-H, J = 8.1, 7.5, 1.3 Hz), 7.85 (dd, 1H, 5-H, J = 7.7, 1.2 Hz); 13C NMR δ 45.75,
48.89, 77.18, 116.28, 121.22, 123.39, 126.63, 126.66, 126.78, 127.17, 127.58, 128.00, 128.05, 128.59,
128.79, 136.19, 137.27, 140.56, 141.19, 171.43, 192.99. Anal. Calcd for C29H24N2O2: C, 80.53; H, 5.59;
N, 6.48. Found: C, 80.57; H, 5.67; N, 6.31.
1-Benzyl-3-phenyl-3-phenylaminoquinoline-2,4(1H,3H)-dione (4Ff). Colorless crystals, mp 217–
221 °C (benzene); IR 3369, 3086, 3057, 3033, 3004, 2971, 2932, 1708, 1676, 1599, 1495, 1465, 1453,
1446, 1437, 1377, 1362, 1320, 1308, 1260, 1243, 1214, 1179, 1164, 1112, 1080, 1052, 1035, 1006, 1000,
992, 839, 773, 764, 758, 748, 707, 690, 694, 684, 620, 607, 540, 525, 506, 489, 462, 436 cm–1; 1H NMR δ
5.29, 5.61 (2d, each, 1H, CH2, J = 16.4 Hz), 6.36 (d, 2H, J = 7.9 Hz), 6.59 (dd, 1H, J = 7.2, 7.1 Hz), 6.82
(s, 1H, NH), 7.04 (dd, 2H, J = 7.8, 7.7 Hz), 7.18 (dd, 1H, J = 7.5, 7.5 Hz), 7.2-7.5 (m, 12H), 7.63 (dd, 1H,
13
7-H, J = 7.4, 7.4 Hz), 7.88 (dd, 1H, 5-H, J = 7.2, 0.7 Hz); C NMR δ 45.54, 74.90, 114.14, 116.58,
116.72, 120.76, 123.57, 126.77, 127.22, 127.36, 128.06, 128.21, 128.33, 128.52, 129.02, 129.34, 135.34,
136.08, 136.56, 140.88, 145.89, 170.65, 191.87. Anal. Calcd for C28H22N2O2: C, 80.36; H, 5.30; N, 6.69.
Found: C, 80.23; H, 5.25; N, 6.48.
General Procedure for the Synthesis of 3-Methylaminoquinoline-2,4(1H,3H)-diones (4Ab, Bb, Cb,

Db, Eb, Fb). To a stirred suspension of methylamine hydrochloride (270 mg, 4 mmol) and powdered
potassium carbonate (1.11 g, 8 mmol) in DMF (10 mL), 3-chloroquinoline-2,4(1H,3H)-dione (2) (2
mmol) was added at rt during 30 min. The resulting mixture was stirred at rt for the time indicated in
Table 1. The reaction mixture was then poured into ice-water (100 mL) and the precipitated product (4)
was filtered off. From the aqueous phase second part of 4 was obtained by extraction into benzene (4×10
mL). Crystallisation of the combined parts of the crude product (4) from the solvents indicated below
afforded 3-methylaminoquinoline-2,4(1H,3H)-diones (4Ab, 4Bb, 4Cb, 4Db, 4Eb, 4Fb) in the yields as
shown in Table 1.
3-Butyl-3-methylaminoquinoline-2,4(1H,3H)-dione (4Ab). Colorless crystals, mp 107–111 °C
(benzene–cyclohexane); IR 3353, 3272, 3186, 3114, 3057, 2992, 2951, 2926, 2867, 1698, 1658, 1612,
1
1596, 1505, 1485, 1461, 1435, 1371, 1317, 1233, 1159, 1133, 936, 910, 856, 761, 665 cm–1; H NMR δ
0.75 (t, 3H, CH3 of butyl, J = 6.9 Hz), 1.08-1.21 (m, 4H, 2- and 3-H of butyl), 1.70-1.73 (m, 2H, 1-H of
butyl), 2.08 (s, 3H, N-CH3), 2.47 (s, 1H, 3-NH), 7.07-7.17 (m, 2H, 6- and 8-H), 7.61 (t, 1H, 7-H, J = 7.2
13
Hz), 7.77 (d, 1H, 5-H, J = 7.4 Hz), 10.92 (s, 1H, 1-H); C NMR δ 13.57, 22.10, 25.00, 31.06, 73.63,
116.23, 119.21, 122.53, 126.53, 136.15, 141.53, 172.60, 196.18. Anal. Calcd for C14H18N2O2: C, 68.27; H,
7.37; N, 11.37. Found: C, 68.07; H, 7.11; N, 11.65.
3-Benzyl-3-methylaminoquinoline-2,4(1H,3H)-dione (4Bb). Colorless crystals, mp 166–169 °C (ethyl
acetate); IR 3340, 3219, 3184, 3069, 2920, 1702, 1689, 1664, 1611, 1593, 1485, 1370, 1290, 1160, 1151,
1
935, 763, 698 cm–1; H NMR δ 2.08 (s, 3H, CH3), 2.59 (br s, 1H, 3-NH), 3.04, 3.09 (each d, each, 1H,
PhCH2, J = 12.4 Hz), 6.92 (d, 1H, 8-H, J = 8.1 Hz), 6.94-6.98 (m, 2H, 3- and 5-H of phenyl), 7.04 (dt, 1H,
6-H, J = 7.5, 0.8 Hz), 7.07-7.15 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.49 (dt, 1H, 7-H, J = 7.7, 1.5 Hz),
7.69 (dd, 1H, 5-H, J = 7.9, 1.4 Hz), 10.90 (s, 1H, 1-H); 13C NMR δ 30.90, 44.88, 74.18, 116.06, 119.45,
122.43, 126.28, 126.71, 127.64, 129.89, 133.96, 136.08, 141.36, 171.78, 195.83. Anal. Calcd for
C17H16N2O2: C, 72.84; H, 5.75; N, 9.99. Found: C, 72.96; H, 5.57; N, 10.10.
3-Methylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Cb). Colorless crystals, mp 189–194 °C
(benzene); IR 3357, 3309, 3190, 3118, 3059, 2993, 2964, 2927, 2871, 2799, 2750, 2681, 1702, 1660,
1613, 1592, 1503, 1484, 1459, 1451, 1434, 1413, 1384, 1361, 1337, 1321, 1272, 1250, 1239, 1203, 1193,
1176, 1167, 1160, 1138, 1113, 1084, 1036, 1027, 1004, 996, 970, 963, 950 cm–1; 1H NMR δ 2.22 (s, 3H,
CH3), 2.91 (s, 1H, 3-NH), 7.09 (dd, 1H, 6-H, J = 7.7, 7.7 Hz), 7.13 (d, 1H, 8-H, J = 8.2 Hz), 7.25-7.41 (m,
5H, phenyl protons), 7.60 (dd, 1H, 7-H, J = 7.7, 8.2 Hz), 7.71 (d, 1H, 5-H, J = 7.7 Hz), 11.24 (s, 1H, 1-
13
H); C NMR δ 31.59, 77.15, 116.36, 119.18, 122.82, 126.50, 127.08, 128.40, 128.62, 136.30, 137.70,
141.12, 171.50, 193.83. Anal. Calcd for C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C, 72.52; H,

5.04; N, 10.22.
1-Methyl-3-methylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Db). Colorless crystals, mp 115–
118 °C (benzene–cyclohexane); IR 3340, 3330, 3066, 2961, 2808, 1703, 1692, 1660, 1599, 1487, 1470,
1451, 1356, 1299, 1255, 1170, 1105, 980, 770, 756, 742 cm–1; 1H NMR δ 2.20 (s, 3H, 3-NCH3), 2.92 (br
s, 1H, NH), 3.53 (s, 3H, 1-CH3), 7.17 (t, 1H, 6-H, J = 7.5 Hz), 7.25-7.32 (m, 5H, phenyl protons), 7.38 (d,
13
1H, 8-H, J = 8.4 Hz), 7.69 (ddd, 1H, 7-H, J = 8.4, 7.7, 1.6 Hz), 7.76 (dd, 1H, 5-H, J = 7.7, 1.6 Hz); C
NMR δ 29.86, 31.59, 77.69, 115.80, 120.71, 123.14, 126.62, 127.26, 128.50, 128.64, 136.23, 137.65,
142.13, 170.99, 192.79. Anal. Calcd for C17H16N2O2: C, 72.84; H, 5.75; N, 9.99. Found: C, 73.22; H,
5.78; N, 9.95.
1-Methyl-3-methylamino-1-phenylquinoline-2,4(1H,3H)-dione (4Eb). Colorless crystals, mp 153–
155 °C (benzene); IR 3336, 3091, 3042, 2989, 2974, 2945, 2860, 2798, 1697, 1664, 1598, 1594, 1493,
1482, 1456, 1437, 1433, 1420, 1417, 1365, 1360, 1336, 1304, 1276, 1272, 1250, 1214, 1190, 1172, 1161,
1151, 1108, 1075, 1048, 1043, 1026, 1023, 1002, 977, 907, 843, 816, 800, 771, 748, 734, 700, 680, 669,
658, 646, 518, 487, 448, 432 cm–1; 1H NMR δ 1.47 (s, 3H, CCH3), 2.17 (s, 3H, NCH3), 2.67 (s, 1H, NH),
6.34 (d, 1H, 8-H, J = 8.3 Hz), 7.18 (dd, J = 7.4, 7.4 Hz, 1H, 6-H), 7.34-7.64 (m, 6H, 7-H and phenyl
13
protons), 7.91 (dd, 1H, 5-H, J = 7.6, 0.9 Hz); C NMR δ 23.34, 30.73, 69.89, 116.31, 119.69, 122.81,
127.18, 128.67, 129.13, 130.05, 135.53, 137.55, 143.51, 172.25, 194.67. Anal. Calcd for C17H16N2O2: C,
72.84; H, 5.75; N, 9.99. Found: C, 73.06; H, 5.63; N, 9.72.
1-Benzyl-3-methylamino-3-phenylquinoline-2,4(1H,3H)-dione (4Fb). Colorless crystals, mp 120–
124 °C (cyclohexane); IR 3300-3600 (br), 3359, 3055, 3029, 2980, 2951, 2927, 2852, 2792, 1771, 1707,
1671, 1598, 1494, 1488, 1465, 1456, 1446, 1371, 1361, 1314, 1270, 1212, 1180, 1163, 1111, 1080, 1027,
1
969, 959, 901, 762, 738, 698, 601, 532, 457, 440 cm–1; H NMR δ 2.27 (s, 3H, CH3), 3.04 (s, 1H, NH),
5.29-5.51 (m, 2H, CH2), 7.14 (dd, 1H, 6-H, J = 7.5, 7.5 Hz), 7.20-7.38 (m, 11H, 8-H and phenyl protons),
7.57 (dd, 1H, 7-H, J = 7.4, 7.4 Hz), 7.82 (d, 1H, 5-H, J = 7.5 Hz); 13C NMR δ 31.66, 45.55, 77.68, 116.26,
121.15, 123.37, 126.56, 126.74, 127.16, 127.55, 128.60, 128.67, 136.18, 137.39, 141.13, 171.44, 192.96.
Anal. Calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C, 77.51; H, 5.80; N, 7.52.
General Procedure for the Synthesis of Primary Amines (4Aa, 4Ba, 4Ca, 4Da, 4Ea, 4Fa) with in situ
Generated Ammonia. Powdered potassium carbonate (1.11 g, 8 mmol) was added portionwise to a
stirred suspension of ammonium chloride (214 mg, 4 mmol) in DMF (10 mL) under cooling with ice-bath
during 5 min. To the resulting stirred and cooled mixture a solution of 2 (2 mmol) in DMF (10 mL) was
added dropwise during 30 min. The stirring was continued at rt for the time indicated in Table 1 and then

worked-up, depending on the product (4), as follows.
- 4Aa: The above obtained reaction mixture was poured into ice-water and filtered. The filtrate was
repeatedly extracted with benzene until the extract was free of the product. The extract was dried, filtered,
and evaporated to dryness. The residue was dissolved in a mixture of benzene (20 mL) and hydrochloric
acid (5%, 20 mL). Layers were separated and aqueous layer was made alkaline with concentrated aqueous
ammonia. Amine (4Aa) was extracted into benzene and the extract was dried over potassium carbonate,
and evaporated to dryness.
- 4Ba and 4Da: After the above reaction mixture was poured into ice-water a part of the precipitated
amine (4) was filtered off. From the filtrate, the second part of the amine (4) was extracted with benzene
(the extract was dried over potassium carbonate and evaporated to dryness). Combined portions of crude
amine (4) were dissolved in a mixture of benzene (20 mL) and hydrochloric acid (5%, 20 mL). Layers
were separated and the aqueous layer was made alkaline with concentrated aqueous ammonia and the
precipitated amine (4) was filtered off.
- 4Ca and 4Ea: The above obtained reaction mixture was poured into ice-water and filtered. The filtrate
was repeatedly extracted with benzene until the extract was free of the product (15 × 10 mL and 8×30 mL
for 4Ca and 4Ea, respectively). The filtrate was dried over potassium carbonate and evaporated to
dryness.
- 4Fa: After the above reaction mixture was poured into ice-water a part of the precipitated amine (4Fa)
was filtered off. From the filtrate, second part of the amine (4Fa) was obtained by extraction into benzene
(3×10 mL, the extract was dried over potassium carbonate and evaporated to dryness). Combined portions
of thus obtained crude amine (4Fa) were purified by column chromatography using solvent system S as
eluant.
After the isolation, the crude amines (4Aa, 4Ba, 4Ca, 4Da, 4Ea, and 4Fa) were crystallized from the
solvents indicated below. The yields of the purified products are in Table 1. The physical and analytical
data are listed as follows.
3-Amino-3-butylquinoline-2,4(1H,3H)-dione (4Aa). Colorless crystals, mp 114–116 °C (benzene); IR
3408, 3342, 3237, 2958, 2927, 2863, 1705, 1673, 1612, 1596, 1484, 1450, 1378, 1363, 1314, 1232, 1182,
1
1156, 1020, 956, 949, 757, 689, 680, 668 cm–1; H NMR δ 0.76 (t, 3H, CH3, J = 6.9 Hz), 1.08-1.28 (m,
4H, 2- and 3-H of butyl), 1.52-1.71 (m, 2H, 1-H of butyl), 2.10 (br s, 2H, NH2), 7.09 (d, 1H, 8-H, J = 8.1
Hz), 7.12 (t, 1H, 6-H, J = 7.6 Hz), 7.59 (dt, 1H, 7-H, J = 7.7, 1.5 Hz), 7.74 (dd, 1H, 5-H, J = 7.7, 1.3 Hz),
13
10.78 (br s, 1H, 1-H); C NMR δ 13.64, 21.95, 24.96, 41.64, 68.28, 116.10, 118.47, 122.47, 126.70,
135.77, 141.46, 173.28, 196.11. Anal. Calcd for C13H16N2O2: C, 67.22; H, 6.94; N, 12.06. Found: C,
66.84; H, 6.91; N, 11.82.

3-Amino-3-benzylquinoline-2,4(1H,3H)-dione (4Ba). Colorless crystals, mp 204–206 °C (methanol),
lit.,7 mp 193–195 °C (ethanol); IR 3391, 3322, 3184, 3059, 2994, 2921, 1702, 1655, 1613, 1594, 1485,
1
1442, 1399, 1285, 1257, 1231, 1163, 1080, 939, 888, 858, 848, 759, 698 cm–1; H NMR δ 2.09 (s, 2H,
NH2), 2.97 (s, 2H, CH2Ph), 6.95-7.02 (m, 2H, 3- and 5-H of phenyl), 7.02 (d, 1H, 8-H, J = 7.9 Hz), 7.10
(dt, 1H, 6-H, J = 7.6, 0.9 Hz), 7.13-7.20 (m, 4H, 6-H, 2-, 4-, and 6-H of phenyl), 7.56 (dt, 1H, 7-H, J =
13
7.7, 1.5 Hz), 7.71 (dd, 1H, 5-H, J = 7.8, 1.5 Hz), 10.85 (s, 1H, 1-H); C NMR δ 48.16, 69.09, 116.08,
118.59, 122.51, 126.58, 126.77, 127.57, 129.94, 134.12, 135.82, 141.40, 172.23, 195.21.
3-Amino-3-phenylquinoline-2,4(1H,3H)-dione (4Ca). Colorless crystals, mp 205–208 °C (benzene); IR
3385, 3311, 3189, 3126, 3074, 3056, 2993, 2924, 2869, 1704, 1664, 1613, 1595, 1483, 1453, 1435, 1369,
1319, 1250, 1232, 1192, 1178, 1158, 1112, 1007, 957, 603, 884, 876, 824, 777, 764, 745, 700, 690, 680,
660, 584, 531, 496, 446, 406 cm–1; 1H NMR δ 2.59 (s, 2H, NH2), 7.10 (dd, 1H, 6-H, J = 7.9, 7.4 Hz), 7.14
(d, 1H, 8-H, J= 8.3 Hz), 7.23-7.33 (m, 3H, 2-, 4-, and 6-H of phenyl), 7.36-7.41 (m, 2H, 3- and 5-H of
phenyl), 7.60 (ddd, 1H, 7-H, J = 8.3, 7.2, 1.3 Hz), 7.70 (dd, 1H, 5-H, J = 7.7, 1.1 Hz), 11.13 (s, 1H, 1-H);
13C NMR δ 70.57, 116.33, 118.62, 122.77, 125.47, 127.12, 128.04, 128.63, 136.12, 140.46, 141.36,
172.12, 194.07. Anal. Calcd for C15H12N2O2: C, 71.42; H, 4.79; N, 11.10. Found: C, 71.55; H, 4.68; N,
10.95.
3-Amino-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (4Da). Colorless crystals, mp 132–135 °C
(benzene–cyclohexane); IR 3379, 3303, 3071, 3046, 2948, 1701, 1660, 1602, 1490, 1469, 1448, 1357,
1
1301, 1253, 1190, 1101, 999, 867, 829, 776, 764, 701, 666 cm–1; H NMR δ 2.63 (s, 2H, NH2), 3.50 (s,
3H, CH3), 7.18 (t, 1H, 6-H, J = 7.5 Hz), 7.22-7.32 (m, 5H, phenyl protons), 7.39 (d, 1H, 8-H, J = 8.4 Hz),
7.69 (dt, 1H, 7-H, J = 7.8, 1.3 Hz), 7.75 (dd, 1H, 5-H, J = 7.3, 1.3 Hz); 13C NMR δ 29.85, 71.13, 115.75,
120.23, 123.09, 125.61, 127.24, 128.10, 128.65, 136.09, 140.57, 142.37, 171.68, 193.30. Anal. Calcd for
C16H14N2O2: C, 72.16; H, 5.30; N, 10.52. Found: C, 71.93; H, 5.21; N, 10.35.
3-Amino-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (4Ea). Colorless crystals, mp 164–167 °C
(benzene–cylohexane); IR 3200-3600 (br), 3378, 3311, 3090, 3065, 2985, 2931, 1709, 1671, 1599, 1494,
1481, 1459, 1368, 1334, 1300, 1241, 1199, 1177, 1161, 1106, 1073, 1025, 1001, 981, 968, 891, 845, 803,
1
793, 769, 703, 663, 647, 518, 487, 451, 439, 426, 404 cm–1; H NMR (CDCl3) δ 1.72 (s, 3H, CH3), 2.23
(s, 2H, NH2), 6.47 (d, 1H, 8-H, J = 8.2 Hz), 7.13-7.63 (m, 7H, 6-H, 7-H, and phenyl protons), 8.02 (dd,
13
1H, 5-H, J = 7.7, 1.6 Hz); C NMR (CDCl3) δ 31.12, 66.19, 76.63, 116.84, 119.60, 123.51, 128.06,
129.13, 135.52, 137.21, 143.63, 173.72, 195.84. Anal. Calcd for C16H14N2O2: C, 72.17; H, 5.30; N, 10.52.
Found: C, 72.57; H, 5.30; N, 10.15.

3-Amino-1-benzyl-3-phenylquinoline-2,4(1H,3H)-dione (4Fa). Colorless crystals, mp 121–123 °C
(cyclohexane); IR 3384, 3309, 3065, 3045, 3024, 2985, 1701, 1664, 1600, 1490, 1464, 1455, 1446, 1368,
1319, 1309, 1251, 1218, 1184, 1168, 1108, 1029, 997, 950, 806, 777, 763, 749, 731, 719, 696, 688, 669,
659, 601, 535, 524, 502, 468, 442, 409 cm–1; 1H NMR δ 2.72 (s, 2H, NH2), 5.32, 5.39 (each d, each, 1H,
CH2, J = 16.6 Hz), 7.15 (dd, 1H, J = 7.5, 7.5 Hz), 7.21-7.33 (m, 11H), 7.57 (ddd, 1H, 7-H, J = 8.4, 7.3,
13
1.6 Hz), 7.82 (dd, 1H, 5-H, J = 7.7, 1.6 Hz); C NMR δ 45.59, 71.29, 116.21, 120.73, 123.28, 125.77,
126.74, 127.16, 127.53, 128.26, 128.50, 128.72, 136.04, 136.27, 140.43, 141.48, 172.39, 193.46. Anal.
Calcd for C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C, 76.86; H, 5.30; N, 8.04.
General Procedure for the Preparation of 3-Azidoquinoline-2,4(1H,3H)-diones (5). To a stirred
solution of 2 or 3 (10 mmol) in DMF (45 mL), sodium azide (975 mg, 15 mmol) was added in small
portions during 0.5 h at rt. The reaction mixture was stirred for additional 1.5 h and then poured into ice-
water (200 mL). The precipitated product (4) was filtered, washed with water and crystallized from the
solvent indicated below.
3-Azido-3-butylquinoline-2,4(1H,3H)-dione (5A). Colorless crystals, mp 112–114 °C (cyclohexane); IR
3239, 2965, 2937, 2904, 2857, 2106, 1723, 1708, 1689, 1611, 1498, 1482, 1467, 1372, 1360, 1306, 1290,
1
1271, 1241, 1159, 1151, 1111, 989, 915, 883, 775, 745, 671 cm–1; H NMR δ 0.78 (t, 3H, CH3, J = 7.0
Hz), 1.12-1.28 (m, 4H, 2- and 3-H of butyl), 1.80-1.98 (m, 2H, 1-H of butyl), 7.11 (d, 1H, 8-H, J = 8.1
Hz), 7.16 (t, 1H, 6-H, J = 7.7 Hz), 7.64 (dt, 1H, 7-H, J = 7.7, 1.5 Hz), 7.77 (dd, 1H, 5-H, J = 7.8, 1.3 Hz),
11.09 (s, 1H, NH); 13C NMR δ 13.50, 21.56, 25.20, 36.82, 74.70, 116.43, 118.37, 122.91, 126.96, 136.40,
141.19, 168.86, 191.18. Anal. Calcd for C13H14N4O2: C, 60.45; H, 5.46; N, 21.69. Found: C, 60.30; H,
5.42; N, 21.48.
3-Azido-3-benzylquinoline-2,4(1H,3H)-dione (5B). Colorless crystals, mp 159–162 °C (ethanol), lit.,9
mp 151 °C (benzene).
3-Azido-3-phenylquinoline-2,4(1H,3H)-dione (5C). Colorless crystals, mp 170–172 °C (benzene), lit.,9
mp 169 °C (toluene).
3-Azido-1-methyl-3-phenylquinoline-2,4(1H,3H)-dione (5D). Colorless crystals, mp 115–118 °C
(ethanol), lit.,9 mp 128 °C (toluene).
3-Azido-3-methyl-1-phenylquinoline-2,4(1H,3H)-dione (5E). Colorless crystals, mp 119–120 °C
(benzene); IR 3428, 3387, 3346, 3091, 3063, 3044, 3016, 2993, 2971, 2105, 1715, 1685, 1603, 1583,
1491, 1464, 1378, 1333, 1301, 1280, 1248, 1199, 1165, 1127, 1116, 1106, 1069, 1048, 1028, 1003, 984,

1
976, 928, 881, 845, 804, 783, 766, 753, 739, 721, 693, 674, 661, 612, 549, 536, 514, 465, 431 cm–1; H
NMR (CDCl3) δ 1.93 (s, 3H, CH3), 6.49 (d, 1H, 8-H, J = 8.4 Hz), 7.19 (dd, 1H, J = 7.5, 7.5 Hz), 7.19-
7.35 (m, 2H), 7.44 (ddd, 1H, J = 8.6, 7.1, 1.6 Hz), 7.49-7.63 (m, 3H), 8.04 (dd, 5-H, 1H, J = 7.8, 1.5 Hz);
13C NMR (CDCl3) δ 23.44, 70.92, 117.13, 118.94, 123.98, 128.59, 128.75, 129.43, 130.56, 136.30,
136.63, 143.22, 169.66, 191.11. Anal. Calcd for C16H12N4O2: C, 65.75; H, 4.14; N, 19.17. Found: C,
66.06; H, 3.98; N, 18.85.
3-Azido-1-benzyl-1-phenylquinoline-2,4(1H,3H)-dione (5F). Colorless crystals, mp 127–129 °C
(ethanol); IR 3387, 3064, 3038, 3011, 2971, 2941, 2117, 1707, 1682, 1600, 1489, 1466, 1446, 1374, 1336,
1317, 1300, 1273, 1250, 1220, 1169, 1137, 1053, 1031, 1021, 978, 878, 849, 763, 731, 711, 696, 679, 662,
631, 579, 549, 528, 515, 493, 457, 437 cm–1; 1H NMR δ 5.29, 5.41 (each d, each, 1H, CH2, J = 16.6 Hz),
7.17-7.20 (m, 2H, 6- and 8-H), 7.24-7.34 (m, 7H), 7.41-7.45 (m, 3H), 7.55 (ddd, 1H, 7-H, J = 8.2, 7.5, 1.6
13
Hz), 7.86 (dd, 1H, J = 7.6, 1.5 Hz); C NMR δ 46.39, 78.09, 116.33, 120.78, 123.61, 126.71, 126.78,
127.21, 127.53, 128.47, 129.55, 130.14, 132.82, 135.88, 136.24, 140.96, 167.90, 188.64. Anal. Calcd for
C22H16N4O2: C, 71.73; H, 4.38; N, 15.21. Found: C, 71.89; H, 4.36; N, 14.82.
General Procedure for the Reduction of 5 to 4 with Zn/AcOH. To a stirred solution of 3-
azidoquinoline-2,4(1H,3H)-dione (5, 5 mmol) in glacial acetic acid (25 mL), zinc dust (1.7 g, 25 mmol)
was added portionwise during 1 h under cooling to 20 °C. The reaction mixture was stirred for additional
0.5 h at rt and the precipitate was filtered off. The filtrate was evaporated in vacuo to dryness and
dissolved in a mixture of benzene (25 mL) and hydrochloric acid (5%, 25 mL). Layers were separated.
The aqueous layer was made alkaline with ammonia (10%) and the precipitated product (4) was filtered
off.
By-product 4-hydroxy-2(1H)-quinolone (1) can be isolated from the above benzene layer by extraction
into aqueous sodium hydroxide and subsequent precipitation from the aqueous layer with concentrated
hydrochloric acid.
Reaction of 3-Azido-3-benzylquinoline-2,4(1H,3H)-dione (5B) with Triphenylphosphine. To a stirred
solution of azide (5B) (585 mg, 2 mmol) in dichloromethane (50 mL) the solution of triphenylphosphine
(787 mg, 3 mmol) in dichloromethane (10 mL) was added dropwise during 20 min at 20 °C. Rapid
evolution of nitrogen gas was observed. According to TLC analysis, the reaction mixture consisted of
triphenylphosphine, triphenylphosphine oxide and 3-benzyl-4-hydroxy-2(1H)-quinolone (1B). Compound
(1B) (450 mg, 90%) was isolated by column chromatography using solvent system S.

ACKNOWLEDGEMENTS
This study was supported by the Ministry of Education, Youth and Sports of the Czech Republic and the
Ministry of Education, Science and Sport, Republic of Slovenia (Grant No. P0-0503-0103). The authors
thank to Mrs. H. Geržová (Faculty of Technology, Tomas Bata University in Zlin, Czech Republic) for
technical help, and Drs. Bogdan Kralj and Dušan Žigon (Mass Spectrometry Center, Jožef Stefan Institute
Ljubljana, Slovenia) for mass spectral measurements.
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