A new and efficient procedure for Friedlaender synthesis of quinolines in low melting tartaric acid-urea mixtures

Article abstract of DOI:10.1071/CH12025

A general, efficient and green method for the synthesis of quinoline derivatives via the Friedlaender heteroannulation reaction of 2-aminoaryl ketones and α-methylene ketones has been developed, employing low melting mixtures of L-(+)-tartaric acid and ur

Full text of DOI:10.1071/CH12025

CSIRO PUBLISHING
Aust. J. Chem. 2012, 65, 409–416
Full Paper
http://dx.doi.org/10.1071/CH12025
¨
A New and Efficient Procedure for Friedlander Synthesis
of Quinolines in Low Melting Tartaric Acid-Urea Mixtures
A
B
C
A D
,
Fei-Ping Ma, Gui-Tian Cheng, Zhi-Guo He, and Zhan-Hui Zhang
A
College of Chemistry and Material Science, Hebei Normal University,
Shijiazhuang 050024, P. R. China.
B
Hebei Chemical and Pharmaceutical Vocational Technology College,
Shijiazhuang 050026, P. R. China.
C
College of Resources and Environment, Hebei Normal University,
Shijiazhuang 050024, P. R. China.
D
Corresponding author. Email: zhanhui@126.com
A general, efficient and green method for the synthesis of quinoline derivatives via the Friedla¨nder heteroannulation
reaction of 2-aminoaryl ketones and a-methylene ketones has been developed, employing low melting mixtures of L-(þ)-
tartaric acid and urea derivatives as an inexpensive, non-toxic, easily biodegradable reaction medium. The melt acts as
both the reaction medium and catalyst, furnishing quinolines in high to excellent yields.
Manuscript received: 19 January 2012.
Manuscript accepted: 24 February 2012.
Published online: 27 March 2012.
peptide coupling agent propylphosphonic anhydride (T3PÒ),[24]
o-benzenedisulfonimide,[25] Yb(OTf)3,[26] KHSO4,[27] or neo-
dymium(III) nitrate hexahydrate.[28] Unfortunately, these
approaches are associated with one or more disadvantages such
as the use of harmful organic solvents, harsh reaction conditions,
unsatisfactory yields of the products, long reaction times, or non-
available and costly reagents.
Introduction
Quinolines have attracted much attention for their various
biological and medicinal properties. Many quinoline derivatives
are used as anticancer,[1] antimicrobial,[2] antitubercular,[3]
antimalarial,[4] antiviral,[5] radiosensitizing,[6] antibacterial
and antifungal agents,[7] as well as selective glucocorticoid
receptor agonists.[8] In addition to the medical applications,
quinoline derivatives have been employed in the synthesis of
fungicides, virucides, biocides, alkaloids, rubber chemicals
and flavouring agents. Additionally, they are also used as
polymers, catalysts, corrosion inhibitors, preservatives, and as
solvent for resins and terpenes. Furthermore, these compounds
find applications in chemistry of transition-metal catalyst for
uniform polymerization and luminescence chemistry. Quino-
line derivatives also act as antifoaming agent in refineries.[9]
Therefore, the importance of this heterocyclic motif has pro-
moted the development of practical and diversified synthesis
methods.[10] Among them, the Friedla¨nder reaction is still one
of the simplest and most powerful tools for the synthesis of
quinolines.[11] In its most general and classical form, the
Friedla¨nder reaction involves condensation of an aromatic
2-amino-substituted carbonyl compound with an appropriately
The application of environmentally friendly solvents such as
water,[29] ionic liquids,[30] supercritical fluids,[31] polyethylene
glycol,[32] glycerol,[33] and perfluorinated solvents[34] is one of
the most important areas of green chemistry. Recently, a low
melting eutectic mixture consisting of urea, carbohydrates and
inorganic salts has been introduced as a new alternative sustain-
able solvent for organic transformations.[35] Some organic reac-
tions such as the Stille,[36] Diels-Alder,[37] Heck, or cycloaddition
reactions,[38] and the synthesis of 5-hydroxymethylfurfural,[39]
and glycosyl ureas[40] have been reported to proceed in these low
melting mixtures with excellent yield and selectivity. The
peculiar physical and chemical properties of low melting
mixtures, such as polarity, low toxicity, non-volatility, biode-
gradability, low cost, and ready availability from bulk renew-
able resources without any further modification, prompted us
to extend their use as green solvents in organic synthesis. In
2011, Gore et al. introduced L-(þ)-tartaric acid-DMU (N,N-
dimethylurea) as a novel and green reaction medium for the
synthesis of 3,4-dihydropyrimidin-2-ones.[41] To the best of our
knowledge, there are no previous reports for the synthesis of
quinoline derivatives by using this eutectic mixture as a reaction
medium. As a continuation of our interest in developing efficient
and environmentally benign synthetic methodologies,[42] we
describe here the use of this eutectic mixture as a green solvent
for the synthesis of quinoline derivatives via the Friedla¨nder
substituted carbonyl derivative containing
a
reactive
a-methylene group followed by cyclodehydration. Numerous
catalysts for the Friedla¨nder reaction have been developed
successfully, including ZrO2,[12] Cu3(BTC)2 (BTC ¼ benzene-
1,3,5-tricarboxylate),[13] cuprous triflate,[14] Mg(NTf2)2,[15]
proline,[16] sulfuric acid-modified PEG-6000,[17] sulfonic acid
functionalized ionic liquid,[18] cerium(IV) ammonium
nitrate,[19] nanoporous cage-type aluminosilicate AlKIT-5,[20]
GdCl3ꢀ6H2O,[21] silica gel-supported sodium hydrogen
sulfate,[22]1-butyl-3-methylimidazolium hydrogen sulfate,[23]
Journal compilation Ó CSIRO 2012
www.publish.csiro.au/journals/ajc

410
F.-P. Ma et al.
O
R
R1
R1
R3
R2
O
R
L-(ϩ)-tartaric acid-DMU
70ЊC
R3
ϩ
R2
NH2
N
1
2
3
Scheme 1. Synthesis of quinoline derivatives in L-(þ)-tartaric acid-DMU.
reaction of 2-aminoaryl ketones and a-methylene ketones
(Scheme 1).
entries 32–36). The reaction is very clean and free of side
products, which are generally formed by self-condensation of
ketones under basic conditions.
Results and Discussion
In conclusion, we have developed an innovative, general,
highly efficient, and environmentally-benign method for the
Friedla¨nder synthesis of polysubstituted and polycyclic quino-
lines using low melting mixtures of L-(þ)-tartaric-DMU as a
novel and green reaction medium. This approach presented
herein avoids the use of hazardous acids or base, toxic organic
solvents, and harsh reaction conditions.
The first trials were performed using the model reaction of
2-aminobenzophenone and acetylacetone in various low melt-
ing mixtures under catalyst-free conditions. Unfortunately, no
reaction proceeded in D-(ꢁ)-fructose-DMU, lactose-DMU-
NH4Cl, glucose-urea-CaCl2, glucose-urea-NaCl, sucrose-
choline chloride, and glucose-guanidinium HCl at their minimal
melting temperature. It is also observed that only a trace amount
of product was detected under solvent-free conditions at 1008C.
Bearing in mind that the Friedla¨nder reaction worked well under
acidic or base conditions, we focussed on the melt systems
consisting of an organic acid as one of the melt components.
Fortunately, the desired condensation reaction eventually took
place in L-(þ)-tartaric acid-choline chloride, giving the corre-
sponding quinoline product in 80 % yield. Further studies
showed that the yield could be increased to as high as 92 %
when L-(þ)-tartaric acid-DMU was used. Thus, the use of
L-(þ)-tartaric acid-DMU as the reaction medium not only
avoids the disadvantages of conventional organic solvents, such
as volatility, inflammability, and potential pollution hazards, but
it also results in greatly enhanced reactivity. Moreover, this
simple procedure allowed easy scale-up of the reaction, whereby
90 % yield was obtained in the 50-mmol-scale reaction, indi-
cating that the reaction can be successfully performed at large
scales without significant loss of the yield.
Based on the above results, this process was then extended to
other structurally varied a-methylene ketones to investigate its
scope and generality. Representative results are shown in
Table 1. It can be seen that under similar conditions, a wide
range of ketones containing a reactive a-methylene group can
undergo easy condensation with 2-aminobenzophenone to give
substituted quinolines with fast reaction times and in high yields.
The a-methylene carbonyl compounds used for the preparation
of these quinolines include cycloalkanones, 1,3-diketones, and
1,4-diketones. Interestingly, cyclic ketones such as cyclopenta-
none, cyclohexanone, cycloheptanone, cyclododecanone, 1H-
inden-2(3H)-one and dimedone gave the respective polycyclic
quinoline in high yields. When an unsymmetrical 1,3-diketone
such as 1-benzoylacetone was used, excellent regioselectivity
was obtained (Table 1, entry 2). It is interesting to note that the
reaction tolerated an acid sensitive ketal functional group
(Table 1, entry 8) and afforded the expected quinoline (3h) in
good yield. Acyclic b-keto esters such as methyl acetoacetate,
ethyl acetoacetate, iso-butyl acetoacetate, tert-butyl acetoace-
tate, allyl acetoacetate, and 2-methoxyethyl acetoacetate were
examined. The alkoxy moiety present had little influence on the
reaction, and generally good yields were obtained.
Experimental
Melting points were measured on an X-4 melting point appa-
ratus and are uncorrected. IR spectra were recorded on a
Shimadzu FTIR-8900 spectrophotometer. The 1H NMR
(500 MHz) and 13C NMR (125 MHz) spectra were recorded on a
Bruker DRX-500 spectrometer using CDCl3 as solvent and
TMS as internal standard. Elemental analyses were carried out
on a Vario EL III CHNOS elemental analyzer. All reagents were
purchased from commercial suppliers and used without further
purification.
General Procedure for the Preparation of Quinoline
Derivatives (3)
A mixture of 2-aminoaryl ketone (1.0 mmol) and a-methylene
ketone (1.0 mmol) in 1.5 g L-(þ)-tartaric acid-DMU (30 : 70)
was stirred at 708C. The progress of reaction was monitored by
TLC. After completion of the reaction, the reaction mixture was
cooled to room temperature and water was added. The solid
product that precipitated out was filtered off, washed with water,
and dried to afford the quinolines in good purity. The oily
products were extracted with ethyl acetate (2 ꢂ 10 mL), and the
combined phase was washed with brine (10 mL), dried over
anhydrous Na2SO4, and concentrated under reduced vacuum.
The residue was purified by flash chromatography on silica gel
(eluent: petroleum ether/ethyl acetate) to afford the pure
product.
The spectroscopic data (IR, 1H NMR, 13C NMR) and
elemental analytical data of all new compounds are given below.
2-Methyl-9-phenyl-1,2,3,4-tetrahydroacridine (3f)
n
max (KBr)/cmꢁ1 3060, 2923, 1610, 1569, 1558, 1485, 1398,
1355, 1153, 1029, 761. dH (500 MHz, CDCl3) 1.01(d, J 6.5, 3H),
1.54–1.63 (m, 1H), 1.82–1.92 (m, 1H), 2.03–2.07 (m, 1H), 2.65
(ddd, J 17.0, 5.0, 2.0, 1H), 2.20–2.26 (m, 1H), 3.14–3.21 (m,
1H), 3.30 (ddd, J 17.0, 5.0, 3.5, 1H), 7.23 (t, J 8.0, 2H), 7.31 (d, J
9.0, 2H), 7.48 (t, J 7.5, 1H), 7.51–7.55 (m, 2H), 7.58–7.62 (m,
1H), 8.01 (d, J 8.5, 1H). dC (125 MHz, CDCl3) 21.9, 29.3, 31.2,
33.9, 36.5, 125.4, 125.8, 126.6, 127.7, 127.9, 128.3, 128.4,
128.6, 129.1, 137.1, 146.4, 158.8. Anal. Calc. for C20H19N:
C 87.87, H 7.01, N 5.12. Found: C 88.05, H 6.86, N 4.93 %.
In addition, when 2-aminobenzophenone was replaced by
1-(2-aminophenyl)ethanone, the reaction also led to the forma-
tion of the desired fused quinolines in high yields (Table 1,

Synthesis of Quinolines
411
Table 1. Synthesis of quinoline derivatives in L-(1)-tartaric acid-DMU
Entry
R
R1
Ketone 2
Product 3
Time [h]
Yield [%]A
mp [8C]
Ph
O
O
O
113–114
111–112[19]
1
Ph
H
30
60
25
45
50
90
50
70
60
92
N
3a
Ph
O
O
O
135–136
135–138[17]
Ph
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
H
95
90
92
70
91
96
95
91
Ph
N
3b
Ph
O
114–115
115[21]
O
O
N
3c
Ph
O
O
131–132
131–133[12]
N
3d
3e
Ph
139–140
137[20]
N
Ph
O
129–130
126–128
158–159
N
3f
Ph
N
O
3g
Ph
O
O
O
O
O
N
3h
Ph
N
O
130–131
131–132[19b]
3i
(Continued)

412
F.-P. Ma et al.
Table 1. (Continued)
Entry
R
R1
Ketone 2
Product 3
Time [h]
Yield [%]A
mp [8C]
O
160–161
162–163[19b]
10
Ph
H
80
90
N
3j
Ph
164–165
168–169[43]
O
11
12
Ph
Ph
H
H
50
20
91
93
N
3k
Ph
N
O
O
O
O
O
158–159
156–158[12]
3l
Ph
O
189–190
18727]
13
Ph
H
30
82
N
3m
3n
3o
Ph
O
O
O
131–132
131–133[12]
OMe
OEt
14
15
16
17
18
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
40
45
45
50
40
91
91
92
88
90
OMe
OEt
N
Ph
O
O
O
98–99
99–102[19]
N
O
O
Ph
O
O
O
O
63–64 64[27]
O
O
N
3p
Ph
O
116–117
117–120[23]
O
N
3q
Ph
O
O
O
O
79–80
O
N
3r
(Continued)

Synthesis of Quinolines
413
Table 1. (Continued)
Entry
19
R
R1
Ketone 2
Product 3
Time [h]
Yield [%]A
mp [8C]
Ph
N
O
O
O
O
O
2
O
OMe
Ph
H
60
90
85–86
2
OMe
3s
Ph
O
O
O
20
21
22
23
24
25
26
27
28
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
40
40
70
20
50
65
25
35
40
94
85
85
88
75
95
80
88
86
93–94
O
N
3t
Ph
N
O
Cl
O
O
154–155
157–158[17]
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
3u
Ph
O
O
O
Cl
216–217
214–216[17]
Ph
Ph
N
3v
Ph
O
Cl
130–131
129[21]
O
O
N
3w
Ph
N
O
Cl
164–165
160–162[12]
3x
Ph
O
O
Cl
O
165–166
O
O
N
3y
Ph
O
O
O
Cl
218–219
219–220[19]
N
3z
Ph
O
O
O
Cl
134–135
136–137[17]
OMe
OEt
OMe
OEt
N
3aa
Ph
O
O
O
Cl
104–105
105–107[12]
N
3ab
(Continued)

414
F.-P. Ma et al.
Table 1. (Continued)
Entry
29
R
R1
Cl
Ketone 2
Product 3
Time [h]
Yield [%]A
mp [8C]
Ph
O
O
O
O
Cl
O
Ph
40
90
118–119
N
O
3ac
3ad
3ae
Ph
Cl
O
O
O
O
2 OMe
O
30
31
32
33
34
35
36
Ph
Cl
Cl
H
H
H
H
H
40
75
92
94
85
91
89
90
92
86–87
2
OMe
N
Ph
O
O
O
Cl
O
Ph
124–125
N
O
O
O
oil
oil[15]
Me
Me
Me
Me
Me
120
N
3af
O
O
O
oil
oil[12]
OMe
OEt
90
OMe
OEt
N
3ag
3ah
O
O
O
oil
oil[12]
110
120
90
N
N
O
O
O
O
oil
oil
O
O
3ai
O
O
O
O
2
O
OMe
N
3aj
AIsolated yield.
2-(tert-Pentyl)-9-phenyl-1,2,3,4-tetrahydroacridine (3g)
max (KBr)/cmꢁ1 2964, 2875, 1605, 1487, 1400, 1388, 763.
129.2, 137.1, 146.3, 146.6, 159.4. Anal. Calc. for C24H27N:
C 87.49, H 8.26, N 4.25. Found: C 87.68, H 8.09, N 4.42.
n
dH (500 MHz, CDCl3) 0.76 (s, 3H), 0.77 (t, J 7.5, 3H), 0.81 (s,
3H), 2.28–2.28 (m, 2H), 1.52–1.58 (m, 2H), 2.07–2.10 (m, 1H),
2.29–2.35 (m, 1H), 2.61–2.65 (m, 1H), 3.09–3.16 (m, 1H), 3.30–
3.35 (m, 1H), 7.22–7.24 (m, 2H), 7.29–7.33 (m, 2H), 7.47 (t, J
7.5, 1H), 7.52 (t, J 8.0, 1H), 7.58–7.61 (m, 1H), 8.01 (d, J 8.5,
1H). dC (125 MHz, CDCl3) 8.1, 23.7, 23.8, 23.9, 28.9, 32.4, 34.9,
42.2, 125.3, 125.8, 126.7, 127.8, 128.3, 128.6, 128.7, 128.9,
9-Phenyl-3,4-dihydro-1H-spiro[acridine-2,2’-[1,3]
di-oxolane] (3h)
n
max (KBr)/cmꢁ1 2935, 2879, 1614, 1658, 1558, 1417, 1377,
1257, 1155, 1120, 1060, 947, 763. dH (500 MHz, CDCl3) 2.18
(t, J 7.0, 2H), 2.87 (s, 2H), 3.428 (t, J 7.0, 2H), 3.92–4.03 (m,
4H), 7.26 (d, J 7.0, 2H), 7.33–7.36 (m, 2H), 7.50 (t, J 7.5, 1H),

Synthesis of Quinolines
415
7.55 (t, J 7.5, 1H), 7.63–7.66 (m, 1H), 8.05 (d, J 8.5, 1H).
dC (125 MHz, CDCl3) d: 31.7, 32.2, 37.8, 64.5, 108.0, 125.6,
125.7, 125.8, 126.5, 127.9, 128.5, 128.8, 129.1, 136.6, 146.5,
147.3. Anal. Calc. for C21H19NO2: C 79.47, H 6.03, N 4.41.
Found: C 79.62, H 5.85, N 4.23 %.
iso-Butyl 6-Chloro-2-methyl-4-phenylquinoline-
3-carboxylate (3ac)
n
max (KBr)/cmꢁ1 2920, 1728, 1601, 1218, 1064, 940, 764. dH
(500 MHz, CDCl3) 0.77 (s, 3H), 0.79 (s, 3H), 1.66–1.74 (m, 1H),
2.80 (s, 3H), 3.81 (d, J 6.5, 2H), 7.38–7.40 (m, 2H), 7.51–7.53
(m, 3H), 7.58 (d, J 2.0, 1H), 7.68 (dd, J 7.5, 2.0, 1H), 8.04 (d, J
8.0, 1H). dC (125 MHz, CDCl3) 18.9, 23.8, 27.4, 71.9, 125.2,
125.9, 128.4, 128.8, 129.3, 130.6, 131.1, 132.4, 134.9, 145.1,
146.1, 154.9, 168.4. Anal. Calc. for C21H20ClNO2: C 71.28,
H 5.70, N 3.96. Found: C 71.10, H 5.52, N 4.15 %.
11-Phenyl-7,8,9,10-tetrahydro-6H-cyclohepta[b]
quinoline (3i)
n
max (KBr)/cmꢁ1 2927, 2850, 1579, 1571, 1485, 1398, 1350,
1197, 962, 763. dH (500 MHz, CDCl3) 1.85–1.87 (m, 4H), 2.71
(t, J 5.5, 2H), 3.29 (t, J 5.5, 2H), 3.48–3.50 (m, 2H), 7.23–7.25
(m, 2H), 7.27–7.29 (m, 1H), 7.33 (t, J 7.5, 1H), 7.59 (t, J 7.5,
1H), 8.02 (d, J 8.5, 1H). dC (125 MHz, CDCl3) 27.1, 28.5, 30.7,
31.9, 40.2, 125.6, 126.4, 126.9, 127.6, 128.2, 128.4, 128.6,
129.5, 133.8, 137.7, 145.5, 145.9, 164.8. Anal. Calc. for
C20H19N: C 87.87, H 7.01, N 5.12. Found: C 87.68, H 6.92,
N 4.95 %.
2-Methoxyethyl 6-Chloro-2-methyl-4-phenylquinoline-
3-carboxylate (3ad)
n
max (KBr)/cmꢁ1 2922, 1716, 1579, 1560, 1481, 1404, 1309,
1230, 1132, 1070, 840, 767. dH (500 MHz, CDCl3) 2.81 (s, 3H),
3.30 (s, 3H), 3.32 (t, J 5.0, 2H), 4.19 (t, J 5.0, 2H), 7.38–7.40 (m,
2H), 7.53–7.55 (m, 3H), 7.57 (d, J 2.0, 1H), 7.68 (dd, J 7.5, 2.0,
1H), 8.04 (d, J 8.5, 1H). dC (125 MHz, CDCl3) 23.8, 58.8, 64.2,
69.9, 125.2, 125.9, 127.9, 128.5, 128.8, 129.3, 130.6, 131.2,
132.4, 135.0, 145.5, 146.2, 155.1, 168.1. Anal. Calc. for
C20H18ClNO3: C 67.51, H 5.10, N 3.94. Found: C 67.33,
H 4.95, N 4.12 %.
iso-Butyl 2-Methyl-4-phenylquinoline-3-carboxylate (3r)
n
max (KBr)/cmꢁ1 2974, 1712, 1614, 1581, 1488, 1467, 1407,
1390, 1301, 1238, 1217, 1128, 1068, 974, 767. dH (500 MHz,
CDCl3) 0.75 (s, 3H), 0.76 (s, 3H), 1.63–1.71 (m, 1H), 2.79
(s, 3H), 3.78 (d, J 6.5, 2H), 7.42–7.44 (m, 1H), 7.45–7.49 (m,
3H), 7.59 (d, J 8.5, 1H), 8.07 (d, J 8.5, 1H). dC (125 MHz,
CDCl3) 19.0, 23.9, 27.4, 71.7, 125.1, 126.4, 126.5, 127.7, 128.3,
128.5, 128.9, 129.4, 130.2, 135.7, 145.9, 147.8, 154.5, 168.8.
Anal. Calc. for C21H21NO2: C 78.97, H 6.63, N 4.39. Found:
C 79.16, H 6.80, N 4.58 %.
Allyl 6-Chloro-2-methyl-4-phenylquinoline-
3-carboxylate (3ae)
n
max (KBr)/cmꢁ1 3076, 2925, 1720, 1600, 1581, 1481, 1394,
1307, 1218, 1068, 935, 765. dH (500 MHz, CDCl3) 2.79 (s, 3H),
4.50 (d, J 6.5, 2H), 5.13–5.18 (m, 2H), 5.53–5.61 (m, 1H), 7.35–
7.37 (m, 2H), 7.52–7.54 (m, 3H), 7.56 (d, J 2.0, 1H), 7.68 (dd, J
7.5, 2.0, 1H), 8.03 (d, J 8.5, 1H). dC (125 MHz, CDCl3) 23.8,
66.2, 119.3, 125.3, 125.9, 127.9, 128.5, 129.3, 130.6, 131.1,
131.2, 132.4, 134.9, 145.5, 146.2, 154.9, 167.9. Anal. Calc. for
C20H16ClNO2: C 71.11, H 4.77, N 4.15. Found: C 70.93, H 4.96,
N 3.98 %.
2-Methoxyethyl 2-Methyl-4-phenylquinoline-
3-carboxylate (3s)
n
max (KBr)/cmꢁ1 2929, 1716, 1612, 1564, 1485, 1415, 1294,
1244, 1217, 1130, 1095, 1070, 958, 771. dH (500 MHz, CDCl3)
2.79 (s, 3H), 3.26–3.29 (m, 5H), 4.15 (t, J 5.0, 2H), 7.37–7.39
(m, 2H), 7.42 (t, J 7.5, 1H), 7.47–7.49 (m, 3H), 7.57 (d, J 7.5,
2H), 8.07 (d, J 8.5, 1H). dC (125 MHz, CDCl3) 23.8, 58.8, 64.1,
69.9, 125.1, 126.4, 126.5, 127.1, 128.3, 128.5, 128.9, 129.4,
130.3, 135.8, 146.4, 147.8, 154.7, 168.5. Anal. Calc. for
C20H19NO3: C 74.75, H 5.96, N 4.36. Found: C 74.93, H 6.15,
N 4.20 %.
iso-Butyl 2,4-Dimethylquinoline-3-carboxylate (3ai)
n
max (KBr)/cmꢁ1 2962, 1728, 1589, 1498, 1404, 1373, 1392,
1286, 1232, 1215, 1161, 1055, 758, 648. dH (500 MHz, CDCl3)
1.04 (s, 3H), 1.06 (s, 3H), 2.07–2.15 (m, 1H), 2.68 (s, 3H), 2.73
(s, 3H), 4.22 (d, J 6.5, 2H), 7.56 (t, J 7.5, 1H), 7.73 (t, J 7.5, 1H),
8.01 (d, J 7.5, 1H), 8.03 (d, J 7.5, 1H). dC (125 MHz, CDCl3)
15.8, 19.2, 23.8, 27.8, 71.9, 124.0, 125.8, 126.3, 128.1, 129.3,
130.1, 141.4, 147.1, 154.3, 169.4. Anal. Calc. for C16H19NO2:
C 74.68, H 7.44, N 5.44. Found: C 74.86, H 7.28, N 5.62 %.
Allyl 2-Methyl-4-phenylquinoline-3-carboxylate (3t)
n
max (KBr)/cmꢁ1 3066, 2993, 1712, 1577, 1560, 1485, 1400,
1296, 1232, 1180, 1130, 1066, 931, 767. dH (500 MHz, CDCl3)
3.06 (s, 3H), 4.48 (d, J 7.0, 2H), 5.11–5.16 (m, 2H), 5.52–5.59
(m, 1H), 7.35–7.37 (m, 2H), 7.43 (t, J 7.5, 1H), 7.47–7.50 (m,
3H), 7.58 (d, J 7.5, 2H), 7.72 (td, J 7.5, 2.0, 1H), 8.07 (d, J 8.5,
1H). dC (125 MHz, CDCl3) 23.9, 66.1, 119.1, 125.1, 126.4,
126.5, 127.2, 128.3, 128.5, 128.9, 129.4, 130.3, 131.2, 135.7,
146.4, 147.8, 154.6, 168.2. Anal. Calc. for C20H17NO2: C 79.19,
H 5.65, N 4.62. Found: C 79.01, H 5.48, N 4.80 %.
2-Methoxyethyl 2,4-Dimethylquinoline-
3-carboxylate (3aj)
n
max (KBr)/cmꢁ1 2927, 1728, 1614, 1589, 1568, 1450, 1404,
1288, 1163, 1082, 983, 759. dH (500 MHz, CDCl3) 2.69 (s, 3H),
2.73 (s, 3H), 3.44 (s, 3H), 3.76 (t, J 5.0, 2H), 4.30 (t, J 5.0, 2H),
7.56 (t, J 7.5, 1H), 7.73 (t, J 7.5, 1H), 8.01 (d, J 7.5, 1H), 8.03 (d,
J 7.5, 1H). dC (125 MHz, CDCl3) 15.7, 23.8, 58.9, 64.3, 70.2,
70.3, 124.0, 125.7, 126.3, 127.7, 129.3, 130.1, 141.7, 147.2,
154.4, 169.1. Anal. Calc. for C15H17NO3: C 69.48, H 6.61,
N 5.40. Found: C 69.66, H 6.80, N 5.23 %.
7-Chloro-9-phenyl-3,4-dihydro-1H-spiro[acridine-
2,2’-[1,3]dioxolane] (3y)
n
max (KBr)/cmꢁ1 2916, 2877, 1579, 1479, 1446, 1375, 1145,
1103, 1060, 947, 827, 717. dH (500 MHz, CDCl3) 2.14 (t, J 7.0,
2H), 2.82 (s, 2H), 3.37 (t, J 7.0, 2H), 3.90–4.00 (m, 4H), 7.21
(d, J 7.5, 2H), 7.29 (d, J 7.5, 1H), 7.47–7.50 (m, 1H), 7.52–7.56
(m, 3H), 7.98 (d, J 8.0, 1H). dC (125 MHz, CDCl3) 31.6, 32.2,
37.9, 64.6, 107.8, 124.6, 126.8, 127.2, 128.3, 129.0, 129.6,
130.2, 131.4, 135.9, 144.9, 146.5, 157.8. Anal. Calc. for
C21H18ClNO2: C 71.69, H 5.16, N 3.98. Found: C 71.88,
H 4.98, N 4.16 %.
Supplementary Material
Copies of 1H NMR and 13C NMR spectra of all new compounds
are available on the Journal’s website.
Acknowledgements
We are grateful for financial support from the National Natural Science
Foundation of China (21072042), the Nature Science Foundation of Hebei

416
F.-P. Ma et al.
Province (B2011205031) and the Undergraduate Scientific and Techno-
logical Innovation Project of Hebei Normal University.
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