Synthesis of Novel α-(Acyloxy)-α-(quinolin-4-yl)acetamides by a Three-Component Reaction between an Isocyanide, Quinoline-4-carbaldehyde, and Arenecarboxylic Acids

Article abstract of DOI:10.1002/hlca.201300378

Novel α-(acyloxy)-α-(quinolin-4-yl)acetamides were synthesized by the Passerini three-component reaction between an isocyanide, quinoline-4-carbaldehyde, and arenecarboxylic acids in H₂O. The reactions were carried out in one pot at room temperature with quantitative yields. Copyright

Full text of DOI:10.1002/hlca.201300378

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Helvetica Chimica Acta – Vol. 97 (2014)
Synthesis of Novel a-(Acyloxy)-a-(quinolin-4-yl)acetamides by a Three-
Component Reaction between an Isocyanide, Quinoline-4-carbaldehyde, and
Arenecarboxylic Acids
a
a
b
c
c
´
by Jafar Taran ), Ali Ramazani* ), Sang Woo Joo* ), Katarzyna Slepokura ), and Tadeusz Lis )
a) Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran
(phone: þ 98-241-5152572; fax: þ 98-241-5152477; e-mail: aliramazani@gmail.com)
b) School of Mechanical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea
(e-mail: swjoo@yu.ac.kr)
c) Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie St., PL-50-383 Wrocław
Novel a-(acyloxy)-a-(quinolin-4-yl)acetamides were synthesized by the Passerini three-component
reaction between an isocyanide, quinoline-4-carbaldehyde, and arenecarboxylic acids in H2O. The
reactions were carried out in one pot at room temperature with quantitative yields.
Introduction. – Multicomponent reactions (MCRs) are important for generating
high levels of diversity, as they allow more than two building blocks to be combined in
practical and time-saving one-pot operations that give rise to complex structures by
simultaneous formation of two or more bonds [1]. MCRs contribute to the require-
ments for environmentally friendly processes by reducing synthetic steps, energy
consumption, and waste production.
The high potential of isocyanides for MCRs lies in the diversity of bond-forming
processes available, in their functional group tolerance, and in the high levels of
chemo-, regio-, and stereoselectivity often observed [2 – 5]. Isocyanide-based MCRs
are particularly useful in drug discovery and total syntheses of biologically relevant
natural products [6 – 11].
The quinoline scaffold is prevalent in a variety of pharmacologically active synthetic
and natural compounds [12]. Quinolines are historically among the most important
antimalarial drugs ever used [13].
The Passerini reactions involve an oxo component, an isocyanide, and a
nucleophile. In continuation of our recent studies on isocyanide chemistry [14 – 21],
we report here the Passerini MCR between quinoline-4-carbaldehyde (1), an
isocyanide 2, and arenecarboxylic acids 3 (Scheme 1).
Results and Discussion. – Quinoline-4-carbaldehyde (1), isocyanide derivatives 2,
and aromatic acids 3 in a 1:1:1 ratio were allowed to react at room temperature in
H2O to yield a-(acyloxy)-a-(quinolin-4-yl)acetamides 4a – 4v (Scheme 1 and Table 1).
The one-pot reaction proceeded smoothly and cleanly under mild conditions in H2O,
and is, therefore, considered to be an almost waste-free method. The products were
crystallized from MeOH/H2O or EtOH/H2O, without any further purification, in
quantitative yield in one-pot reactions.
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1. Preparation of a-(Acyloxy)-a-(quinolin-4-yl)acetamides 4a – 4v from Quinoline-4-carbalde-
hyde (1), Isocyanide Derivatives 2, and Arenecarboxylic Acids 3 in H2O
Table 1. Synthesis of a-(Acyloxy)-a-(quinolin-4-yl)acetamides 4a – 4v
Entry
Product
R
Ar
Reaction time [h]
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
cHexa)
cHex
cHex
cHex
cHex
cHex
cHex
cHex
cHex
Ph
1
2
2
1
1
1
1
1
2
3
1
2
1
1
1
1
2
3
2
2
2
3
99
96
96
97
97
98
97
96
97
88
98
96
97
97
98
95
96
87
96
95
96
94
4-tBuꢀC6H4
4-MeꢀC6H4
4-ClꢀC6H4
3-ClꢀC6H4
4-FꢀC6H4
4-BrꢀC6H4
4-IꢀC6H4
4-CNꢀC6H4
Naphthalen-1-yl
Ph
cHex
tBu
tBu
4-tBuꢀC6H4
4-ClꢀC6H4
3-ClꢀC6H4
4-FꢀC6H4
4-BrꢀC6H4
4-CNꢀC6H4
Naphthalen-1-yl
Ph
tBu
tBu
tBu
tBu
tBu
tBu
4s
4t
4u
4v
2,6-Me2ꢀC6H3
2,6-Me2ꢀC6H3
2,6-Me2ꢀC6H3
2,6-Me2ꢀC6H3
4-tBuꢀC6H4
4-ClꢀC6H4
Naphthalen-1-yl
a) cHex, Cyclohexyl.
The structures of the products were deduced from their IR, 1H- and 13C-NMR, and
mass spectra. The mass spectra of the products displayed molecular-ion peaks at the
1
appropriate m/z values. The H-NMR spectrum of 4a exhibited distinct signals for
cyclohexyl CH2 (d(H) 1.15 – 1.94), NꢀCH (3.81 – 3.91), CHꢀO (6.98), NH (6.19), and
aromatic CH groups (7.50 – 8.98). The 1H-decoupled 13C-NMR spectrum of 4a showed
21 distinct resonances arising from cyclohexyl CH2 (d(C) 24.68 – 32.85), NꢀCH (48.66),
and CHꢀO (72.7) groups, aromatic C-atoms (120.1 – 149.8), and an ester C¼O
(164.88), and an amide C¼O group (166.18).
Finally, the structure of 4d was confirmed unambiguously by X-ray single-crystal
analysis (Fig. 1). Centrosymmetric crystals of 4d were formed by exploiting convection
from hexane at 658 (branch tube method) [22].

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A plausible mechanism for the formation of 4a – 4v is proposed in Scheme 2. The
acid 3 protonates carboxaldehyde 1 to form an intermediate, which is then attacked by
the isocyanide 2, leading to the formation of 4 (Scheme 2) [23].
Crystal Structure of 4d. The centrosymmetric space group C2/c indicates that the
crystal contains racemic 4d. The molecular structure of the (S)-enantiomer is shown in
Fig. 1. The conditions for the data collection and the structure refinement parameters
for 4d are given in the Exper. Part. The selected geometrical parameters are compiled in
Table 2.
In 4d, both COOR and CONHR groups are planar, and the whole 2-(cyclo-
hexylamino)-2-oxoethyl 4-chlorobenzoate moiety adopts the extended conformation,
as confirmed by the values of C(12)ꢀN(2)ꢀC(11)ꢀC(10), O(2)ꢀC(10)ꢀC(11)ꢀN(2),
and C(10)ꢀO(2)ꢀC(18)ꢀC(19) torsion angles, which are close to 1808 (see
Scheme 2. Proposed Mechanism for the Formation of 4a – 4v
Fig. 1. X-Ray crystal structure of one enantiomer of 4d (displacement ellipsoids at 50% probability
level). Dashed line indicates the intramolecular CꢀH ··· O contact forming S(7) motif.

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Table 2. Selected Interatomic Distances, Bond Angles, and Torsion Angles of 4d
Bond lengths [ꢂ]
O(1)ꢀC(18)
O(2)ꢀC(18)
O(2)ꢀC(10)
O(3)ꢀC(11)
1.2060(11)
1.3499(10)
1.4369(11)
1.2240(11)
N(2)ꢀC(11)
N(2)ꢀC(12)
C(10)ꢀC(11)
1.3388(12)
1.4636(13)
1.5452(13)
Bond angles [8]
C(18)ꢀO(2)ꢀC(10)
C(11)ꢀN(2)ꢀC(12)
O(2)ꢀC(10)ꢀC(3)
O(2)ꢀC(10)ꢀC(11)
C(3)ꢀC(10)ꢀC(11)
O(3)ꢀC(11)ꢀN(2)
115.36(7)
123.91(8)
107.24(7)
110.70(7)
112.79(7)
125.53(8)
O(3)ꢀC(11)ꢀC(10)
N(2)ꢀC(11)ꢀC(10)
O(1)ꢀC(18)ꢀO(2)
O(1)ꢀC(18)ꢀC(19)
O(2)ꢀC(18)ꢀC(19)
122.24(8)
112.20(7)
123.52(8)
125.50(8)
110.96(7)
Torsion angles [8]
C(18)ꢀO(2)ꢀC(10)ꢀC(3)
C(18)ꢀO(2)ꢀC(10)ꢀC(11)
C(4)ꢀC(3)ꢀC(10)ꢀO(2)
C(4)ꢀC(3)ꢀC(10)ꢀC(11)
C(12)ꢀN(2)ꢀC(11)ꢀC(10)
162.12(7)
ꢀ 74.46(9)
52.28(10)
ꢀ 69.84(10)
176.27(8)
O(2)ꢀC(10)ꢀC(11)ꢀO(3)
C(3)ꢀC(10)ꢀC(11)ꢀO(3)
O(2)ꢀC(10)ꢀC(11)ꢀN(2)
C(11)ꢀN(2)ꢀC(12)ꢀC(13)
C(10)ꢀO(2)ꢀC(18)ꢀC(19)
ꢀ 18.03(11)
102.13(9)
163.81(7)
ꢀ 153.44(9)
ꢀ 177.46(7)
Table 2). The molecule has the C¼Oamide,CꢀOester syn-periplanar conformation
(O(2)ꢀC(10)ꢀC(11)ꢀO(3) amounting to ꢀ 18.03(11)8). As seen from the torsion
angle C(18)ꢀO(2)ꢀC(10)ꢀC(11) (ꢀ74.46(9)8), the a-(acyloxy)acetamide fragment
is twisted at the O(2)ꢀC(10) bond, with the ester and amide C¼O C-atoms in
sc orientation to each other. The orientation of the quinolin-4-yl (QN) moiety in
relation to the a-(acyloxy)acetamide (defined by the C(4)ꢀC(3)ꢀC(10)ꢀO(2) and
C(4)ꢀC(3)ꢀC(10)ꢀC(11) torsion angles; Table 2) is accompanied by the intramolec-
ular CꢀHQN ··· O¼Camide contact (forming S(7) motif), as shown in Fig. 1.
In the crystal lattice of 4d, the adjacent molecules related by the action of the glide
plane ((S) and (R)-isomers) are joined to each other by N(2)ꢀH ··· N(1) H-bonds
(Table 3) to form chains running down the c-axis (Fig. 2). The interchain contacts are
provided by weak CꢀH ··· O bonds and p ··· p interactions (centroid ··· centroid
distance, 3.6672(11) ꢂ; centroid ··· plane perpendicular distance, 3.5310(4) ꢂ), as well
as by the halogen Cl ··· Cl interactions (3.302(1) ꢂ), giving rise to a 3D network.
Table 3. Proposed H-Bonds and Close Contacts for 4d
DꢀH ··· Aa)
DꢀH [ꢂ]
0.85(2)
0.95
0.99
0.95
H ··· A [ꢂ]
D ··· A [ꢂ]
DꢀH ··· A [8]
163(2)
133
151
119
N(2)ꢀH ··· N(1)i)
2.24(2)
2.57
2.54
2.58
2.44
3.0647(13)
3.2906(14)
3.4349(14)
3.1566(14)
3.0829(14)
C(5)ꢀH ··· O(3)
C(14)ꢀH ··· O(3)ii)
C(20)ꢀH ··· O(1)iii)
C(21)ꢀH ··· O(1)iii)
0.95
125
a
i
) Symmetry codes: ) x, ꢀ y þ 2, z ꢀ 1/2; ii) ꢀ x þ 3/2, ꢀ y þ 3/2, ꢀ z þ 1; iii) x, ꢀ y þ 1, z þ 1/2.

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Fig. 2. The molecules of 4d joined to each other via the NꢀH ··· N contacts (dashed lines), forming chains
down the c-axis. Intramolecular CꢀH ··· O contacts are also shown. Different enantiomers are indicated
by light and dark grey. Viewed down the b-axis. Symmetry code is given in Table 3.
Conclusions. – We have synthesized and characterized novel a-(acyloxy)-a-
quinolin-4-yl)acetamides by the Passerini three-component reaction between quino-
line-4-carbaldehyde (1), an isocyanide 2, and arenecarboxylic acids 3 in H2O. This
procedure offers significant advantages such as operational simplicity, mild reaction
conditions, enhanced rates, ease of isolation of products, cleaner reaction profiles, and
H2O as medium, rendering it a useful protocol for the synthesis of these compounds.
This work is funded by the Grant 2011-0014246 of the National Research Foundation of Korea. The
authors thank University of Zanjan and University of Wrocław for the support and guidance.
Experimental Part
General. Starting materials and solvents were purchased from Merck (Germany), Fluka (Switzer-
land), and Acros (USA), and were used without further purification. The reactions were monitored by
TLC and NMR techniques, which indicated that there were no side-products. M.p.: Electrothermal 9100
1
apparatus. IR Spectra: Mattson-1000 FT-IR spectrophotometer; ˜n in cmꢀ1. H- and 13C-NMR spectra:
1
Bruker 400 spectrometer; 400 and 100 MHz for H and 13C, resp.; in CDCl3; d in ppm rel. to Me4Si as
internal standard, J in Hz. MS: Finnigan-MAT 8430 mass spectrometer; at 20 eV; in m/z (rel. %).
General Procedure for the Syntheses of 4a – 4v. Isocyanide 2 (0.2 mmol) was added to a magnetically
stirred soln. of quinoline-4-carbaldehyde (1; 0.2 mmol) and arenecarboxylic acids 3 (0.2 mmol) in H2O
(5 ml) at r.t. over 5 min. The mixture was stirred at r.t. for the time specified in Table 1, after which single-
spot products were obtained by TLC. H2O was removed under reduced pressure, and the products were
purified by TLC and then crystallized.
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl Benzoate (4a). Yield: 99%. Colorless crystals.
M.p. 157 – 1598. IR (KBr): 3419, 3280, 2930, 2855, 1719, 1660, 1565, 1269, 1097. 1H-NMR: 1.15 – 1.94 (m,
5 CH2); 3.81 – 3.91 (m, NꢀCH); 6.19 (d, J ¼ 8, NH); 6.98 (s, CHꢀO); 7.50 – 8.98 (m, 11 arom. H).
13C-NMR: 24.68 – 32.85 (5 CH2); 48.66 (NꢀCH); 72.70 (CHꢀO); 120.13, 124.05, 127.46, 128.80, 129.79,
129.88, 133.99, 149.83 (11 arom. CH); 126.19, 130.09, 141.48, 148.47 (4 C); 164.88 (ester C¼O); 166.18
(amide C¼O). EI-MS: 388 (8), 263 (42), 158 (91), 130 (11), 105 (100), 77 (38), 55 (35).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-(1,1-Dimethylethyl)benzoate (4b). Yield: 97%.
Colorless crystals. M.p. 167 – 1698. IR (KBr): 3420, 3298, 2932, 2852, 1723, 1658, 1555, 1272, 1099.
1H-NMR: 1.14 – 1.41 (m, 2 CH2(b)); 1.36 (s, 3 Me); 1.61 – 1.73 (m, 2 CH2(a)); 1.91 – 1.97 (m, CH2(g));
3.81 – 3.91 (m, NꢀCH); 6.28 (d, J ¼ 8, NH); 7.00 (s, CHꢀO); 7.52 – 8.96 (m, 10 arom. H). 13C-NMR: 31.06

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t
(3 Me); 24.70, 24.72, 25.39, 32.83, 32.91 (5 CH2); 35.26 (Cq of Bu); 48.58 (NꢀCH); 72.47 (CHꢀO);
120.02, 124.12, 125.58, 127.42, 129.76, 129.80, 130.07, 157.98 (10 arom. CH); 125.90, 126.25, 141.71, 148.47,
149.80 (5 C); 164.47 (ester C¼O); 166.30 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Methylbenzoate (4c). Yield: 95%. Colorless
crystals. M.p. 141 – 1438. IR (KBr): 3450, 3301, 2928, 2852, 1720, 1660, 1550, 1260, 1110. 1H-NMR: 1.11 –
1.97 (m, 5 CH2); 2.45 (s, Me); 3.82 – 3.89 (m, NꢀCH); 6.23 (d, J ¼ 7.2, NH); 6.99 (s, CHꢀO); 7.29 – 8.96
(m, 10 arom. H). 13C-NMR: 21.79 (Me); 24.66, 24.69, 25.37, 32.78, 32.86 (5 CH2); 48.59 (NꢀCH); 72.47
(CHꢀO); 120.02, 124.11, 125.96, 127.44, 129.53, 129.79, 129.92, 130.00, 149.77 (10 arom. CH); 126.24,
129.02, 141.72, 145.00, 148.39 (5 C); 164.86 (ester C¼O); 166.29 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Chlorobenzoate (4d). Yield: 97%. Colorless
crystals. M.p. 187 – 1898. IR (KBr): 3445, 3271, 2932, 2851, 1734, 1700, 1569, 1253, 1095. 1H-NMR: 1.13 –
1.69 (m, 5 CH2); 3.81 – 3.90 (m, NꢀCH); 6.116 (d, J ¼ 8, NH); 6.968 (s, CHꢀO); 7.29 – 8.98 (m, 10 arom.
H). 13C-NMR: 24.66 – 32.84 (5 CH2); 48.75 (NꢀCH); 72.94 (OꢀCH); 120.31, 123.89, 127.61, 129.16,
130.13, 131.26, 149.81 (10 arom. CH); 126.10, 127.20, 140.57, 141.14, 148.43 (5 C); 164.19 (ester C¼O);
165.94 (amid C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 3-Chlorobenzoate (4e). Yield: 97%. Colorless
crystals. M.p. 171 – 1738. IR (KBr): 3432, 3276, 2929, 2852, 1728, 1656, 1563, 1247, 1129. 1H-NMR: 1.12 –
1.96 (m, 5 CH2); 3.80 – 3.90 (m, NꢀCH); 6.122 (d, J ¼ 8, NH); 6.96 (s, CHꢀO); 7.29 – 8.97 (m, 10 arom.
H). 13C-NMR: 24.65 – 32.82 (5 CH2); 48.77 (NꢀCH); 73.02 (CHꢀO); 120.28, 123.83, 127.62, 128.02,
129.89, 129.92, 130.10, 130.22, 133.99, 149.92 (10 arom. CH); 126.06, 130.52, 134.96, 140.89, 148.56 (5 C);
163.89 (ester C¼O); 165.86 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Fluorobenzoate (4f). Yield: 98%. Colorless
crystals. M.p. 178 – 1808. IR (KBr): 3430, 3271, 2923, 2851, 1734, 1655, 1568, 1255, 1085. 1H-NMR: 1.08 –
1.97 (m, 5 CH2); 3.81 – 3.90 (m, NꢀCH); 6.08 (d, J ¼ 8, NH); 6.96 (s, CHꢀO); 7.16 – 8.98 (m, 10 arom. H).
13C-NMR: 24.66 – 32.84 (5 CH2); 48.72 (NꢀCH); 72.88 (CHꢀO); 115.92, 116.14, 120.31, 123.89, 127.50,
129.78, 130.26, 132.51, 132.60, 149.95 (10 arom. CH); 125.04, 126.11, 141.03, 148.63, 165.02 (5 C); 164.04
(ester C¼O); 166.06 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Bromobenzoate (4g). Yield: 97%. Colorless
crystals. M.p. 167 – 1698. IR (KBr): 3435, 3295, 2928, 2854, 1732, 1658, 1554, 1254, 1098. 1H-NMR: 1.07 –
1.95 (m, 5 CH2); 3.79 – 3.88 (m, NꢀCH); 6.241 (d, J ¼ 8, NH); 6.93 (s, CHꢀO); 7.57 – 8.94 (m, 10 arom.
H). 13C-NMR: 24.66 – 32.83 (5 CH2); 48.75 (NꢀCH); 72.98 (CHꢀO); 120.36, 123.86, 127.53, 127.68,
129.80, 131.35, 132.14, 149.98 (10 arom. CH); 126.07, 129.24, 130.27, 140.87, 148.64 (5 C); 164.37 (ester
C¼O); 165.97 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Iodobenzoate (4h). Yield: 96%. Colorless
crystals. M.p. 146 – 1488. IR (KBr): 3438, 3277, 2930, 2853, 1728, 1656, 1562, 1247, 1129. 1H-NMR:
1.23 – 1.97 (m, 5 CH2); 3.82 – 3.89 (m, NꢀCH); 6.06 (d, J ¼ 8, NH); 6.98 (s, CHꢀO); 7.29 – 9.00 (m, 10
arom. H). 13C-NMR: 24.65 – 32.82 (5 CH2); 48.79 (NꢀCH); 73.01 (CHꢀO); 120.27, 123.86, 127.67, 128.02,
129.92, 129.98, 130.10, 130.51, 133.99, 134.96, 149.78 (10 arom. CH); 126.09, 131.18, 138.18, 141.11, 148.37
(5 C); 163.88 (ester C¼O); 165.83 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl 4-Cyanobenzoate (4i). Yield: 97%. Yellow crys-
tals. M.p. 189 – 1908. IR (KBr): 3426, 3302, 2931, 2854, 2232, 1736, 1658, 1550, 1251, 1104. 1H-NMR: 1.03 –
1.95 (m, 5 CH2); 3.79 – 3.88 (m, NꢀCH); 6.04 (d, J ¼ 8, NH); 6.92 (s, CHꢀO); 7.58 – 8.96 (m, 10 arom. H).
13C-NMR: 24.64 – 32.80 (5 CH2); 48.93 (NꢀCH); 73.52 (CHꢀO); 120.72, 123.68, 127.74, 129.98, 130.39,
130.42, 132.50, 149.99 (10 arom. CH); 117.22, 117.71, 125.95, 132.69, 140.30, 148.67 (6 C); 163.67 (ester
C¼O); 165.57 (amide C¼O).
2-(Cyclohexylamino)-2-oxo-1-(quinolin-4-yl)ethyl Naphthalene-1-carboxylate (4j). Yield: 88%.
Yellow crystals. M.p. 163 – 1658. IR (KBr): 3420, 3236, 2851, 1721, 1670, 1526, 1250, 1138. 1H-NMR:
1.15 – 1.97 (m, 5 CH2); 3.85 – 3.92 (m, NꢀCH); 6.29 (d, J ¼ 8, NH); 7.13 (s, CHꢀO); 7.55 – 9.00 (m, 10
arom. H). 13C-NMR: 24.71 – 32.88 (5 CH2); 48.68 (NꢀCH); 72.69 (CHꢀO); 120.12, 124.07, 124.54,
125.44, 126.67, 127.58, 128.37, 128.77, 129.92, 130.08, 130.56, 134.50, 149.81 (13 arom. CH); 125.54, 126.23,
131.41, 133.87, 141.70, 148.42 (6 C); 165.50 (ester C¼O); 166.29 (amide C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl Benzoate (4k). Yield: 98%. Colorless
crystals. M.p. 207 – 2098. IR (KBr): 3426, 3304, 2964, 2925, 1720, 1664, 1557, 1252, 1111. 1H-NMR: 1.39 (s,

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3 Me); 6.18 (s, NH); 6.93 (s, CHꢀO); 7.49 – 9.00 (m, 11 arom. H). 13C-NMR: 28.64 (3 Me); 52.06 (Me3C);
72.74 (CHꢀO); 120.14, 124.04, 127.54, 128.76, 128.83, 129.86, 129.96, 134.01, 149.72 (11 arom. CH);
126.30, 128.31, 141.93, 148.31 (5 C); 164.80 (ester C¼O); 166.17 (amide C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-(1,1-Dimethylethyl)benzoate (4l).
Yield: 84%. Colorless crystals. M.p. 159 – 1618. IR (KBr): 3460, 3346, 2962, 2869, 1720, 1670, 1538,
1264, 1116. 1H-NMR: 1.36 (s, 3 Me); 1.40 (s, 3 Me); 6.24 (s, NH); 6.93 (s, CHꢀO); 7.51 – 8.97 (m, 10 arom.
H). 13C-NMR: 28.66 (3 Me); 31.06 (3 Me); 35.25 (Me3C); 51.98 (CꢀNH); 72.56 (CHꢀO); 120.06, 124.09,
125.84, 127.40, 129.72, 129.76, 130.09, 149.81 (10 arom. CH); 125.94, 126.32, 141.95, 148.48, 157.94 (5 C);
164.72 (ester C¼O); 166.36 (amide C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-Chlorobenzoate (4m). Yield: 97%.
Colorless crystals. M.p. 124 – 1268. IR (KBr): 3434, 3224, 3077, 2968, 1720, 1676, 1581, 1265, 1096.
1H-NMR: 1.38 (s, 3 Me); 6.09 (s, NH); 6.92 (s, CHꢀO); 7.48 – 9.01 (m, 10 arom. H). 13C-NMR: 28.61
(3 Me); 52.14 (CꢀNH); 72.99 (CHꢀO); 120.41, 123.81, 127.55, 128.59, 129.16, 129.81, 130.29, 131.24,
150.01 (10 arom. CH); 126.15, 127.24, 140.54, 141.09, 148.67 (5 C); 164.17 (ester C¼O); 166.01 (amide
C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 3-Chlorobenzoate (4n). Yield: 97%.
Colorless crystals. M.p. 158 – 1608. IR (KBr): 3434, 3315, 3069, 2975, 1727, 1663, 1551, 1246, 1129.
1H-NMR: 1.38 (s, 3 Me); 6.00 (s, NH); 6.89 (s, CHꢀO); 7.43 – 9.00 (m, 10 arom. H). 13C-NMR: 28.61
(3 Me); 57.17 (CꢀNH); 73.08 (CHꢀO); 120.34, 123.83, 127.64, 127.99, 129.91, 130.10, 133.96, 134.95,
149.84 (10 arom. CH); 126.15, 130.18, 130.54, 141.23, 148.47 (5 C); 163.85 (ester C¼O); 165.84 (amide
C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-Fluorobenzoate (4o). Yield: 98%.
Colorless crystals. M.p. 178 – 1808. IR (KBr): 3430, 3308, 2979, 2963, 1720, 1667, 1560, 1260, 1114.
1H-NMR: 1.38 (s, 3 Me); 6.034 (s, NH); 6.89 (s, CHꢀO); 7.15 – 8.98 (m, 10 arom. H). 13C-NMR: 28.61
(3 Me); 52.11 (CꢀNH); 72.92 (CHꢀO); 115.93, 116.15, 120.36, 123.88, 127.54, 129.83, 130.22, 132.48,
132.58, 149.90 (10 arom. CH); 125.06, 126.19, 141.35, 148.56, 165.02, 167.56 (5 C); 163.99 (ester C¼O);
166.06 (amide C¼O). EI-MS: 380 (7), 281 (34), 158 (100), 123 (71), 95 (27), 75 (13), 57 (67).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-Bromobenzoate (4p). Yield: 95%.
Colorless crystals. M.p. 177 – 1798. IR (KBr): 3439, 3222, 3076, 2967, 1719, 1675, 1589, 1265, 1096.
1H-NMR: 1.37 (s, 3 Me); 6.00 (s, NH); 6.88 (s, CHꢀO); 7.59 – 8.98 (m, 10 arom. H). 13C-NMR: 28.61
(3 Me); 52.14 (CꢀNH); 73.01 (CHꢀO); 120.38, 123.84, 127.59, 129.88, 130.19, 131.32, 132.16, 149.87 (10
arom. CH); 126.16, 127.69, 129.25, 141.26, 148.51 (5 C); 164.31 (ester C¼O); 165.95 (amide C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-Cyanobenzoate (4q). Yield: 96%.
Yellow crystals. M.p. 117 – 1198. IR (KBr): 3444, 3228, 3076, 2967, 2232, 1720, 1677, 1596, 1270, 1103.
1H-NMR: 1.35 (s, 3 Me); 5.83 (s, NH); 6.86 (s, CHꢀO); 7.63 – 9.00 (m, 10 arom. H). 13C-NMR: 28.58
(3 Me); 52.32 (CꢀNH); 73.55 (CHꢀO); 117.25, 123.71, 127.86, 130.13, 130.42, 132.51, 132.69, 149.75 (10
arom. CH); 117.70, 120.73, 126.10, 130.21, 140.87, 148.50 (6 C); 163.61 (ester C¼O); 165.48 (amide C¼O).
2-[(1,1-Dimethylethyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl Naphthalene-1-carboxylate (4r). Yield:
87%. Yellow crystals. M.p. 154 – 1568. IR (KBr): 3501, 3228, 3075, 2972, 1720, 1676, 1569, 1270, 1059.
1H-NMR: 1.40 (s, 3 Me); 6.22 (s, NH); 7.03 (s, CHꢀO); 7.54 – 9.00 (m, 13 arom. H). 13C-NMR: 28.67
(3 Me); 52.10 (CꢀNH); 72.79 (CHꢀO); 120.15, 124.04, 124.55, 125.42, 126.66, 127.57, 128.36, 128.78,
129.88, 130.12, 130.54, 134.51, 149.85 (13 arom. CH); 125.52, 126.31, 131.42, 133.88, 141.89, 148.47 (6 C);
165.45 (ester C¼O); 166.35 (amide C¼O).
2-[(2,6-Dimethylphenyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl Benzoate (4s). Yield: 96%. Colorless
crystals. M.p. 197 – 1998. IR (KBr): 3427, 3250, 3030, 2923, 1726, 1666, 1535, 1263, 1116. 1H-NMR: 2.09 (s,
2 Me); 7.21 (s, CHꢀO); 7.65 (s, NH); 7.02 – 9.02 (m, 14 arom. H). 13C-NMR: 18.28 (2 Me); 73.18
(CHꢀO); 119.86, 124.17, 127.79, 128.33, 128.65, 128.86, 129.97, 134.13, 135.38, 149.96 (14 arom. CH);
125.95, 127.61, 130.23, 132.39, 140.98, 148.62 (7 C); 165.10 (ester C¼O); 165.53 (amide C¼O). EI-MS: 410
(5), 263 (25), 158 (40), 130 (8), 105 (100), 91 (7), 77 (44), 51 (14).
2-[(2,6-Dimethylphenyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-(1,1-Dimethylethyl)benzoate (4t).
Yield: 95%. Colorless crystals. M.p. 162 – 1648. IR (KBr): 3422, 3262, 2964, 2867, 1723, 1660, 1530,
1268, 1113. 1H-NMR: 1.37 (s, Me3C); 2.11 (s, 2 Me); 7.22 (s, CHꢀO); 7.66 (s, NH); 7.03 – 9.01 (m, 13 arom.
H). 13C-NMR: 18.30 (2 Me); 31.07 (Me3C); 35.28 (Me3C); 73.01 (CHꢀO); 119.77, 124.29, 125.88, 127.76,

Helvetica Chimica Acta – Vol. 97 (2014)
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128.32, 129.90, 130.01, 135.38, 149.71 (13 arom. CH); 125.78, 126.02, 127.61, 132.42, 141.50, 148.33, 158.10
(8 C); 160.01 (ester C¼O); 165.60 (amide C¼O).
2-[(2,6-Dimethylphenyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl 4-Chlorobenzoate (4u). Yield: 96%.
Colorless crystals. M.p. 212 – 2148. IR (KBr): 3447, 3252, 3031, 1733, 1663, 1591, 1255, 1117. 1H-NMR: 2.06
(s, 2 Me); 7.18 (s, CHꢀO); 7.54 (s, NH); 7.02 – 9.04 (m, 13 arom. H). 13C-NMR: 18.25 (2 Me); 73.36
(CHꢀO); 120.00, 124.09, 125.93, 127.89, 127.92, 128.38, 129.26, 129.90, 130.32, 131.34, 132.26, 135.33,
149.58 (13 arom. CH); 127.04, 128.73, 128.91, 131.43, 140.77, 141.23, 148.11 (8 C); 164.37 (ester C¼O);
165.16 (amide C¼O).
2-[(2,6-Dimethylphenyl)amino]-2-oxo-1-(quinolin-4-yl)ethyl Naphthalene-1-carboxylate (4v).
Yield: 94%. Yellow crystals. M.p. 193 – 1958. IR (KBr): 3435, 3260, 3030, 2922, 1712, 1669, 1591, 1243,
1164. 1H-NMR: 2.12 (s, 2 Me); 7.35 (s, CHꢀO); 7.55 (s, NH); 7.02 – 9.05 (m, 16 arom. H). 13C-NMR: 18.33
(2 Me); 73.10 (CHꢀO); 119.84, 124.17, 124.54, 125.46, 126.70, 127.74, 127.84, 128.36, 128.47, 128.80, 130.09,
130.81, 134.71, 135.42, 149.87 (16 arom. CH); 125.29, 126.00, 130.18, 130.49, 132.38, 133.91, 141.27, 148.50
(9 C); 165.63 (ester C¼O); 165.72 (amide C¼O).
X-Ray Crystal-Structure Determination of 4d (Fig. 1)1). The crystallographic measurement for 4d
was performed on a Kuma KM4CCD k-geometry four-circle diffractometer with graphite-monochrom-
atized MoKa radiation. The data were collected at 100(2) K using an Oxford Cryosystems cooler. Data
were corrected for Lorentz and polarization effects. Data collection, cell refinement, and data reduction
and analysis were carried out with the KM4CCD software, CRYSALIS CCD and CRYSALISRED, resp.
[24]. Empirical absorption correction was applied to the data with the use of CRYSALIS RED. The
structure was solved by direct methods with the SHELXS-97 program [25] and refined by a full-matrix
least-squares technique based on F2 using SHELXL-2013 [25] with anisotropic thermal parameters for
the non-H-atoms. The H-atoms were found in difference Fourier maps, and, in the final refinement cycles,
the C-bonded H-atoms were repositioned in their calculated positions and refined using a riding model,
with CꢀH of 0.95 – 1.00 ꢂ, and with Uiso(H) ¼ 1.2 Ueq(C). The figures were made using DIAMOND
program [26].
Crystallographic Data for 4d. C24H23ClN2O3, Mr 422.89; colorless bloc; crystal size, 0.50 ꢁ 0.30 ꢁ
0.20 mm; monoclinic; space group C2/c (No. 15); a ¼ 33.010(9), b ¼ 11.261(3), c ¼ 11.380(3) ꢂ, b ¼
92.12(3)8, V ¼ 4227(2) ꢂ3, T¼ 100(2) K, Z ¼ 8, 1calc ¼ 1.329 g cmꢀ3, m ¼ 0.21 mmꢀ1 (for MoKa, l ¼
0.71073 ꢂ), Tmin ¼ 0.857, Tmax ¼ 1.000; 36202 reflections measured, 10168 unique (Rint ¼ 0.035), 7626
observed (I > 2s(I)); q range, 3.11 – 36.968, parameters, 275, restraints, 0; R1 ¼ 0.048, wR2 ¼ 0.134
(observed refl.); goodness-of-fit, S, 1.06; largest difference in peak and hole, D1max and D1min, 0.64 and
ꢀ 0.24 eꢂꢀ3, resp.
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Received October 21, 2013