Three-component one-pot synthesis of quinoline-furan conjugates from acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde

Article abstract of DOI:10.1016/j.tet.2013.08.009

We have developed a facile and efficient method for the synthesis of functionalized novel furylquinolines. A variety of quinoline-furan conjugates were obtained via the condensation of 2-chloroquinoline-3-carbaldehyde with acetylenecarboxylates and isocyanides in good to excellent yields.

Full text of DOI:10.1016/j.tet.2013.08.009

Accepted Manuscript
Three-component one-pot synthesis of quinoline-furan conjugates from
acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde
Mehdi Ghandi, Nahid Zarezadeh
PII:
S0040-4020(13)01268-4
10.1016/j.tet.2013.08.009
TET 24697
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 19 June 2013
Revised Date: 20 July 2013
Accepted Date: 5 August 2013
Please cite this article as: Ghandi M, Zarezadeh N, Three-component one-pot synthesis of quinoline-
furan conjugates from acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde,
Tetrahedron (2013), doi: 10.1016/j.tet.2013.08.009.
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ACCEPTED MANUSCRIPT
Graphical abstract
Three-component one-pot synthesis of quinoline-furan conjugates from
acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde
Mehdi Ghandi*, Nahid Zarezadeh
1

ACCEPTED MANUSCRIPT
Three-component one-pot synthesis of quinoline-furan conjugates from
acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde
Mehdi Ghandi*, Nahid Zarezadeh
aSchool of Chemistry, College of Science, University of Tehran,
Tehran, P.O. Box 14155 6455, Iran
Abstract. We have developed a facile and efficient method for the synthesis of functionalized
novel furylquinolines. A variety of quinoline-furan conjugates were obtained via the
condensation of 2-chloroquinoline-3-carbaldehyde with acetylenecarboxylates and isocyanides
in good to excellent yields.
Keywords: 2-chloroquinoline-3-carbaldehyde; Isocyanide; 2-Chloro-3-(furan-2-yl)quinolines
1. Introduction
Multicomponent reactions (MCRs) are one-pot processes in which three or more different
substrates react for the preparation of target materials.1 These reactions which have gained much
attention during the past years, are frequently occurring not through a single-step procedure, but
rather by several sequential steps or multicomponent cascade or domino reactions.2 Simplicity,
greater efficiency and atom economy with generation of diverse and complex “drug-like”
heterocyclic compounds in one-pot transformation are some of the advantages of these reactions.
* Corresponding author, Tel: +9821 61112250; fax: +9821 66495291;
e-mail address: ghandi@khayam.ut.ac.ir (M. Ghandi).
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The isocyanide-based multicomponent reactions (IMCRs) have emerged particularly as powerful
tools in this area.3
The reaction of isocyanides and acetylene compounds, first described by Winterfeld in 1969
is perhaps the founding basis for a large class of new accessible scaffolds.4 This reaction initially
affords a zwitterionic adduct, which might undergo cycloaddition to various electrophiles such as
simple aldehydes, imines, activated alkenes, quinones and aza-aromatic systems to form a
variety of novel compounds including amino-furans, pyrroles, highly substituted
cyclopentadienoids and spirolactones.5 Whereas the cycloaddition of isocyanides and dimethyl
acetylenedicarboxylate has been known with simple aldehydes, more complex structures such as
3-formylchromones have rarely been used in these reactions.6 Furan can be regarded as one of
the most important heterocyclic compounds due to the presence of this core structure in many
natural and important pharmaceutical compounds like ascorbic acid,7 ranitidine,8 phomactin A,9
azimilide,10 dantrolene,11 nitrofurazone,12 perillene,13 teubrevin G and teulepicin,14 as well as
numerous experimental drug candidates in a wide range of therapeutic areas. Furan derivatives
exhibit a wide spectrum of considerable biological activities that include gastrointestinal motility
activity,15 antimicrobial,16 antispasmodic,17 antiarrhythmic,18 antitumor properties19 and several
other potentially useful activities.20
On the other hand, quinoline-containing compounds have been extensively used in medicinal
chemistry because of various biological activities such as antiinflammatory,21 antimalarial,22
anticancer,23 analgesic,24 and antifungal.25
Because of the importance of these heterocycles and significant enhancement expectation in
biological activity in the presence of two different heterocyclic motifs in a single molecule,26we
became interested in the synthesis of quinoline-furan conjugates. Herein, we report the facile
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synthesis of 2-chloro-3-(furan-2-yl)quinolines via one-pot, three-component condensation of 2-
chloroquinoline-3-carbaldehyde, acetylenecarboxylates and isocyanides in acetonitrile.
2. Results and discussion
Initially, compounds 3a-c were prepared on the basis of the previously reported procedure
(Scheme 1).27
Scheme 1. Preparation of 2-chloroquinoline-3-carbaldehydes 3a-c.
Subsequent three-component reactions employing 3a-c, dialkyl acetylenedicarboxylates 4a-b
°
and various isocyanides 5a-c in acetonitrile at 40 C afforded the novel substituted (2-
chloroquinolin-3-yl)furan-3,4-dicarboxylates 6a–r in moderate to excellent yields (Scheme 2,
Table 1). The structure of compounds 6a-r were confirmed by their analytical and spectral data.
For example, the mass spectra of 6a displayed the molecular ion peak at 416 for M+ ([35Cl]) and
418 for M+ ([37Cl]) consistent with the molecular structure. The IR spectrum of 6a displayed
characteristic absorption bands at 3330 and 1716 cm-1 due to N-H and C=O stretching vibrations,
1
respectively. The H NMR spectrum of 6a consisted characteristic singlets at δ 1.49 (9H), 3.73
(3H), 3.78 (3H), and a broad singlet at δ 6.98 (1H) relevant to CMe3, OMe, OMe, and N-H,
respectively. The presence of two C=O groups was further confirmed by the appearance of two
signals at δ 164.2 and 165.1 in the 13C NMR spectrum of 6a. The 1H NMR and 13C NMR spectra
of 6b-r were similar to that of 6a.
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Although the precise mechanism is not known, a mechanistic postulate as shown in Scheme
3 may be invoked to rationalize the formation of 6a. It is conceivable that the in situ generated
Scheme 2. furylquinolines 6a-r obtained from three component reactions.
Huisgen’s zwitterion I by the 1:1 interaction between DMAD (4a) and tert-butyl isocyanide (5a)
attacks preferentially the C-4 of 2-chloroquinoline-3-carbaldehyde (3a), leading to intermediate
II. Product 6a is subsequently obtained via an allowed [1,5] H shift.
CO2Me
MeO2C
MeO2C
N
C(Me)3
C
N
C(Me)3
CO2Me
I
O
4a
5a
H
N
Cl
3a
CO2Me
MeO2C
H
CO2Me
NH
MeO2C
[1,5] H shift
N
O
O
C(Me)3
C(Me)3
N
N
Cl
Cl
II
6a
Scheme 3. Mechanism evoked for the formation of 6a.
The effect of introducing either a modest or strong electron-donating group into the 2-
chloroquinoline-3-carbaldehyde ring results in a small decrease in the product yields (entries 7
Table 1
Structures of products 6a–r obtained from 3a-c, DMAD or DEAD 4a-b and isocyanides 5a-c
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Entry
1
Quinolines
Isocyanide
acetylenecarboxylate
DMAD
Product
Structure
Yield (%)
90
6a
2
3
4
5
6
DMAD
DMAD
DEAD
DEAD
DEAD
90
95
92
96
92
6b
6c
6d
6e
6f
7
8
9
DMAD
DMAD
DMAD
88
90
86
6g
6h
6i
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TnQT
able1
Entry
Quinolines
Isocyanide
acetylenecarboxylate
DEAD
Product
Product 6
Yield (%)
85
10
11
12
13
14
15
6j
6k
6l
DEAD
DEAD
DMAD
DMAD
DMAD
87
91
76
6m
6n
6o
80
78
16
DEAD
75
6p
17
18
DEAD
DEAD
78
81
6q
6r
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to 18, Table 1). This behavior supports the suggested mechanism if the zwitterion I addition to
the double bond of 3a (Scheme 3) becomes rate limiting step. Therefore, obtaining lower yields
of 2g-r is anticipated.
3. Conclusion
In conclusion,
a
number of 2-chloroquinoline-3-carbaldehyde with dialkyl
acetylenecarboxylates and isocyanides underwent one-pot multicomponent reactions in
acetonitile, affording a variety of biologically interesting quinoline-furan conjugates. These new
structures broaden the scaffolds that are accessible through Michael addition/intramolecular
cyclization and [1,5] H shift rearrangement cascade and many of them may represent interesting
pharmacophores.
4. Experimental section
4.1. General information
All commercially available chemicals and reagents were purchased from Merck Chemical
Company and used without further purification. Melting points were determined with an
Electrothermal model 9100 apparatus and are uncorrected. IR spectra were recorded on a
Shimadzu 4300 spectrophotometer, in cm-1. 1H and 13C NMR spectra were recorded on a Bruker
DRX-500-AVANCE spectrometer at 300 (1H) and 75 MHz (13C) using CDCl3 as solvent and
with the residual solvent signal as internal reference (CDCl3, 7.24 and 77.0 ppm). Mass spectra
of the products were obtained with an HP (Agilent technologies) 5937 Mass Selective Detector.
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Elemental analyses were carried out by a CHN-Rapid Heraeus elemental analyzer (Wellesley,
MA).
4.2. Representative procedure for the synthesis of 6a-r
To
a
stirred solution of 2-chloroquinoline-3-carbaldehyde (1 mmol) and
acetylenedicarboxylate (1.2 mmol) in CH3CN (10 mL), isocyanide (1.2 mmol) was added. The
mixture was stirred for 12 h at 40 °C. After completion of the reaction as indicated by TLC, the
mixture was cooled to room temperature and the crude solid filtered and recrystallized from
EtOH to afford 6a-r.
4.2.1. Dimethyl 2-(tert-butylamino)-5-(2-chloroquinolin-3-yl)furan-3,4-dicarboxylate (6a). Pale
yellow solid (0.37 g, 90%), mp 139-141 °C; [Found: C, 60.50; H, 4.78; N, 6.76. C21H21ClN2O5
requires C, 60.51; H, 5.08; N, 6.72%]; Rf (20% EtOAc/hexane) 0.35; νmax (KBr) 3330 (NH),
1716 (C=O), 1674 (C=O) cm-1; δH (300 MHz, CDCl3) 1.44 (9H, s, CMe3), 3.73 (3H, s, 3-OMe),
3.78 (3H, s, 4-OMe), 6.98 (1H, br s, NH), 7.55 (1H, t, J 7.5 Hz, Ar), 7.73 (1H, t, J 7.7 Hz, Ar),
7.83 (1H, d, J 8.1 Hz, Ar), 8.00 (1H, d, J 8.4 Hz, Ar), 7.28 (1H, s, Ar); δc (75 MHz, CDCl3)
29.8 (CMe3), 51.2 (3-OMe), 52.3 (4-OMe), 52.9 (CMe3), 87.6 (C-3 of furan), 117.8 (C-4 of
furan), 122.7 (C-5 of furan), 126.4, 127.6, 127.9, 128.3, 131.3, 139.0, 140.2, 147.1, 149.0 (C-Ar
of quinoline), 162.5 (C-2 furan), 164.2 (3-C=O), 165.1 (4-C=O); m/z (EI, 70 eV) 416 (35, M+
[35Cl]), 418 (12, M+ [37Cl]), 402 (2), 388 (2), 360 (79), 328 (69), 313 (12), 293 (51), 278 (8), 265
(20), 241 (46), 233 (6), 214 (19), 205 (6), 190 (86), 177 (17), 162 (61), 127 (29), 101 (26), 83
(24), 64 (61), 57 (100%).
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4.2.2. Dimethyl 2-(2-chloroquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-dicarboxylate (6b). Pale
yellow solid (0.40 g, 90%), mp 171-173 °C; [Found: C, 62.67; H, 5.03; N, 6.41. C23H23ClN2O5
requires C, 62.37; H, 5.23; N, 6.33%]; Rf (20% EtOAc/hexane) 0.30; νmax (KBr) 3370 (NH),
1735 (C=O), 1672 (C=O) cm-1; δH (300 MHz, CDCl3) 1.23-2.02 (10H, m, 5CH2 of cyclohexyl),
3.64-3.68 (1H, m, CHNH of cyclohexyl), 3.73 (3H, s, 3-OMe), 3.79 (3H, s, 4-OMe), 6.73 (1H, d,
J 8.0 Hz, NH), 7.56 (1H, t, J 7.5 Hz, Ar), 7.74 (1H, t, J 7.2 Hz, Ar), 7.84 (1H, d, J 8.0 Hz, Ar),
8.00 (1H, d, J 8.4 Hz, Ar), 8.28 (1H, s, Ar); δc (75 MHz, CDCl3) 24.5 (2CH2), 25.3 (CH2), 33.9
(2CH2), 51.2 (3-OMe), 51.5 (CHNH of cyclohexyl), 52.3 (4-OMe), 86.7 (C-3 of furan), 118.0
(C-4 of furan), 122.8 (C-5 of furan), 126.3, 127.5, 127.9, 128.3, 131.3, 138.9, 140.1, 147.1, 149.1
(C-Ar of quinoline), 162.2 (C-2 furan), 164.1 (3-C=O), 165.0 (4-C=O); m/z (EI, 70 eV) 442
(100, M+ [35Cl]), 444 (33, M+ [37Cl]), 411 (17), 360 (16), 328 (43), 313 (5), 293 (29), 278 (4),
265 (13), 241 (24), 233 (4), 214 (9), 205 (3), 190 (29), 177 (5), 162 (20), 127 (6), 101 (7), 83
(22), 64 (6), 57 (81%).
4.2.3.
Dimethyl
2-(2-chloroquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-3,4-
dicarboxylate (6c). Pale yellow solid (0.45 g, 95%), mp 140-142 °C; [Found: C, 63.48; H, 5.80;
N, 5.95. C25H29ClN2O5 requires C, 63.49; H, 6.18; N, 5.92%]; Rf (20% EtOAc/hexane) 0.38;
νmax (KBr) 3362 (NH), 1724 (C=O), 1666 (C=O) cm-1; δH (300 MHz, CDCl3) 1.01 (9H, s,
CMe3), 1.50 (6H, s, CMe2), 1.77 (2H, s, CH2), 3.74 (3H, s, 3-OMe), 3.79 (3H, s, 4-OMe), 7.11
(1H, br s, NH), 7.57 (1H, t, J 7.5 Hz, Ar), 7.75 (1H, t, J 7.7 Hz, Ar), 7.84 (1H, d, J 8.1 Hz, Ar),
8.02 (1H, d, J 8.4 Hz, Ar), 8.29 (1H, s, Ar); δc (75 MHz, CDCl3) 30.1 (CMe2), 31.4 (CMe3),
31.7 (CMe3), 51.2 (3-OMe), 52.4 (4-OMe), 53.0 (CCH2C), 56.5 (CMe2), 87.3 (C-3 of furan),
117.9 (C-4 of furan), 122.8 (C-5 of furan), 126.4, 127.6, 127.9, 128.3, 131.3, 138.8, 140.2, 147.2,
149.0 (C-Ar of quinoline), 162.4 (C-2 furan), 164.3 (3-C=O), 165.1 (4-C=O); m/z (EI, 70 eV)
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472 (10, M+ [35Cl]), 474 (3, M+ [37Cl]), 442 (28), 416 (6), 402(5), 360 (80), 328 (75), 313 (8),
293 (35), 278 (6), 265 (14), 241 (28), 233 (4), 214 (13), 205 (4), 190 (54), 177 (11), 162 (37),
127 (16), 101 (13), 83 (18), 69 (24), 57 (100%).
4.2.4. Diethyl 2-(tert-butylamino)-5-(2-chloroquinolin-3-yl)furan-3,4-dicarboxylate (6d). Pale
yellow solid (0.41 g, 92%), mp 125-127 °C; [Found: C, 62.11; H, 5.58; N, 6.29. C23H25ClN2O5
requires C, 62.09; H, 5.66; N, 6.30%]; Rf (20% EtOAc/hexane) 0.42; νmax (KBr) 3339 (NH),
1726 (C=O), 1658 (C=O) cm-1; δH (300 MHz, CDCl3) 1.18 (3H, t, J 7.1 Hz, 3-OCH2Me), 1.30
(3H, t, J 7.1 Hz, 4-OCH2Me), 1.44 (9H, s, CMe3), 4.20 and 4.24 (4H, 2q, J 7.1, 7.1 Hz,
2OCH2Me), 6.98 (1H, br s, NH), 7.55 (1H, t, J 7.5 Hz, Ar), 7.73 (1H, t, J 7.7 Hz, Ar), 7.81 (1H,
d, J 8.1 Hz, Ar), 8.00 (1H, d, J 8.4 Hz, Ar), 8.29 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-
OCH2Me), 14.4 (4-OCH2Me), 29.8 (CMe3), 52.8 (CMe3), 59.8 (3-OCH2Me), 61.4 (4-OCH2Me),
87.8 (C-3 of furan), 118.3 (C-4 of furan), 122.8 (C-5 of furan), 126.3, 127.5, 127.8, 128.3, 131.2,
138.5, 140.1, 147.1, 149.0 (C-Ar of quinoline), 162.4 (C-2 furan), 163.9 (3-C=O), 164.7 (4-
C=O); m/z (EI, 70 eV) 444 (45, M+ [35Cl]), 446 (15, M+ [37Cl]), 399 (8), 388 (75), 353 (18), 342
(39), 325 (6), 313 (54), 296 (5), 279 (57), 368 (6), 251 (10), 241 (7), 214 (13), 190 (78), 172
(18), 162 (48), 149 (29), 140 (7), 127 (26), 101 (24), 81 (36), 67 (76), 57 (100%).
4.2.5. Diethyl 2-(2-chloroquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-dicarboxylate (6e). Pale
yellow solid (0.45 g, 96%), mp 142-144 °C; [Found: C, 63.50; H, 5.83; N, 5.96. C25H27ClN2O5
requires C, 63.76; H, 5.78; N, 5.95%]; Rf (20% EtOAc/hexane) 0.38; νmax (KBr) 3357 (NH),
1725 (C=O), 1668 (C=O) cm-1; δH (300 MHz, CDCl3) 1.17-2.04 (16H, consisting 3H, t, J 7.1
Hz, 3-OCH2Me, 3H, t, J 7.1 Hz, 4-OCH2Me, and 10H, m, 5CH2 of cyclohexyl), 3.65-3.68 (1H,
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m, CHNH of cyclohexyl), 4.24 (4H, two overlapped q, J 7.1 Hz, 2OCH2Me), 6.75 (1H, d, J 8.1
Hz, NH), 7.56 (1H, t, J 7.5 Hz, Ar), 7.76 (1H, t, J 7.7 Hz, Ar), 7.84 (1H, d, J 8.1 Hz, Ar), 8.02
(1H, d, J 8.4 Hz, Ar), 8.31 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.4 (4-
OCH2Me), 24.5 (2CH2), 25.4 (CH2), 33.4 (2CH2), 51.5 (CHNH of cyclohexyl), 59.7 (3-
OCH2Me), 61.3 (4-OCH2Me), 86.9 (C-3 of furan), 118.4 (C-4 of furan), 122.8 (C-5 of furan),
126.3, 127.5, 127.8, 128.4, 131.2, 138.4, 140.1, 147.1, 149.3 (C-Ar of quinoline), 162.2 (C-2
furan), 163.8 (3-C=O), 164.6 (4-C=O); m/z (EI, 70 eV) 470 (41, M+ [35Cl]), 472 (14, M+ [37Cl]),
425 (4), 444 (4), 402 (2), 388 (7), 353 (4), 342 (18), 325 (2), 313 (25), 296 (17), 279 (29), 368
(3), 251 (6), 241 (14), 214 (8), 190 (72), 172 (13), 162 (35), 149 (19), 140 (10), 127 (18), 101
(16), 97 (24), 83 (76), 69 (73), 55 (100%).
4.2.6.
Diethyl
2-(2-chloroquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-3,4-
dicarboxylate (6f). Pale yellow solid (0.45 g, 92%), mp 107-109 °C; [Found: C, 64.86; H, 6.71;
N, 5.62. C27H33ClN2O5 requires C, 64.73; H, 6.64; N, 5.59%]; Rf (20% EtOAc/hexane) 0.46;
νmax (KBr) 3316 (NH), 1718 (C=O), 1656 (C=O) cm-1; δH (300 MHz, CDCl3) 1.02 (9H, s,
CMe3), 1.20 (3H, t, J 7.1 Hz, 3-OCH2Me), 1.32 (3H, t, J 7.1 Hz, 4-OCH2Me), 1.51 (6H, s,
CMe2), 1.78 (2H, s, CH2), 4.22 and 4.26 (4H, 2q, J 7.1, 7.1 Hz, 2OCH2Me), 7.11 (1H, br s, NH),
7.58 (1H, t, J 7.5 Hz, Ar), 7.76 (1H, t, J 7.7 Hz, Ar), 7.83 (1H, d, J 8.1 Hz, Ar), 8.03 (1H, d, J
8.4 Hz, Ar), 8.30 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 30.1
(CMe2), 31.5 (CMe3), 31.7 (CMe3), 53.0 (CCH2C), 56.5 (CMe2), 59.7 (3-OCH2Me ), 61.4 (4-
OCH2Me), 87.6 (C-3 of furan), 118.4 (C-4 of furan), 122.9 (C-5 of furan), 126.4, 127.5, 127.8,
128.4, 131.2, 138.4, 140.2, 147.1, 149.1 (C-Ar of quinoline), 162.3 (C-2 furan), 164.0 (3-C=O),
164.7 (4-C=O); m/z (EI, 70 eV) 500 (10, M+ [35Cl]), 502 (3, M+ [37Cl]), 455 (2), 444 (4), 429 (2),
402 (10), 388 (79), 353 (13), 342 (24), 325 (4), 313 (26), 293 (6), 279 (28), 368 (4), 251 (6), 241
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(12), 214 (6), 190 (35), 172 (9), 162 (20), 149 (13), 140 (6), 127 (9), 101 (8), 81 (18), 69 (37), 57
(100%).
4.2.7. Dimethyl 2-(tert-butylamino)-5-(2-chloro-6-methylquinolin-3-yl)furan-3,4-dicarboxylate
(6g). Pale yellow solid (0.38 g, 88%), mp 162-164 °C; [Found: C, 60.92; H, 5.27; N, 6.41.
C22H23ClN2O5 requires C, 61.32; H, 5.38; N, 6.50%]; Rf (20% EtOAc/hexane) 0.35; νmax (KBr)
3328 (NH), 1722 (C=O), 1657 (C=O) cm-1; δH (300 MHz, CDCl3) 1.45 (9H, s, CMe3), 2.51 (3H,
s, Me), 3.73 (3H, s, 3-OMe), 3.79 (3H, s, 4-OMe), 6.99 (1H, br s, NH), 7.55-7.59 (2H, m, Ar),
7.90 (1H, d, J 8.5 Hz, Ar), 8.19 (1H, s, Ar); δc (75 MHz, CDCl3) 21.5 (Me), 29.8 (CMe3), 51.2
(3-OMe), 52.3 (4-OMe), 52.9 (CMe3), 87.6 (C-3 of furan), 117.6 (C-4 of furan), 122.6 (C-5 of
furan), 126.4, 126.7, 128.0, 133.6, 137.7, 139.2, 139.5, 145.7, 148.0 (C-Ar of quinoline), 162.5
(C-2 furan), 164.3 (3-C=O), 165.1 (4-C=O); m/z (EI, 70 eV) 430 (27, M+ [35Cl]), 432 (9, M+
[37Cl]), 402 (7), 388 (12), 374 (42), 339 (39), 327 (7), 307 (42), 292 (6), 279 (22), 265 (2), 255
(29), 228 (13), 204 (53), 190 (14), 176 (47), 167 (15), 149 (19), 140 (39), 115 (28), 97 (19), 83
(26), 69 (52), 57 (100%).
4.2.8. Dimethyl 2-(2-chloro-6-methylquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-dicarboxylate
(6h). White solid (0.41 g, 90%), mp 206-208 °C; [Found: C, 63.05; H, 5.51; N,
6.13 ̟C24H25ClN2O5 requires C, 63.09; H, 5.51; N, 6.13%]; Rf (20% EtOAc/hexane) 0.32; νmax
(KBr) 3359 (NH), 1721 (C=O), 1669 (C=O) cm-1; δH (300 MHz, CDCl3) 1.25-2.05 (10H, m,
5CH2 of cyclohexyl), 2.53 (3H, s, Me), 3.65-3.68 (1H, m, CHNH of cyclohexyl), 3.74 (3H, s, 3-
OMe), 3.80 (3H, s, 4-OMe), 6.73 (1H, d, J 8.1 Hz, NH), 7.57-7.61 (2H, m, Ar), 7.91 (1H, d, J
8.5 Hz, Ar), 8.20 (1H, s, Ar); δc (75 MHz, CDCl3) 21.6 (Me), 24.5 (2CH2), 25.4 (CH2), 33.4
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(2CH2), 51.2 (3-OMe), 51.5 (CHNH of cyclohexyl), 52.3 (4-OMe), 86.6 (C-3 of furan), 117.8
(C-4 of furan), 122.6 (C-5 of furan), 126.4, 126.7, 128.0, 133.6, 137.7, 139.1, 139.5, 145.7, 148.2
(C-Ar of quinoline), 162.2 (C-2 furan), 164.1 (3-C=O), 165.0 (4-C=O); m/z (EI, 70 eV) 456 (16,
M+ [35Cl]), 458 (5, M+ [37Cl]), 430 (17), 402 (10), 388 (9), 374 (29), 339 (32), 327 (9), 307 (35),
292 (6), 279 (20), 265 (3), 255 (24), 231 (15), 204 (48), 188 (14), 176 (29), 167 (20), 149 (36),
140 (21), 115 (19), 97 (25), 81 (40), 69 (79), 57 (100%).
4.2.9. Dimethyl 2-(2-chloro-6-methylquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-
3,4-dicarboxylate (6i). Pale yellow solid (0.42 g, 86%), mp 170-172 °C; [Found: C, 62.72; H,
6.30; N, 5.50. C26H31ClN2O5 requires C, 64.12; H, 6.42; N, 5.75%]; Rf (20% EtOAc/hexane)
0.40; νmax (KBr) 3336 (NH), 1716 (C=O), 1671 (C=O) cm-1; δH (300 MHz, CDCl3) 1.01 (9H, s,
CMe3), 1.50 (6H, s, CMe2), 1.78 (2H, s, CH2), 2.52 (3H, s, Me), 3.74 (3H, s, 3-OMe), 3.79 (3H,
s, 4-OMe), 7.10 (1H, br s, NH), 7.56-7.59 (2H, m, Ar), 7.91 (1H, d, J 8.4 Hz, Ar), 8.19 (1H, s,
Ar); δc (75 MHz, CDCl3) 21.6 (Me), 30.1 (CMe2), 31.4 (CMe3), 31.7 (CMe3), 51.2 (3-OMe),
52.3 (4-OMe), 53.0 (CCH2C), 56.5 (CMe2), 87.3 (C-3 of furan), 117.7 (C-4 of furan), 122.7 (C-5
of furan), 126.4, 126.7, 128.0, 133.6, 137.7, 139.0, 139.6, 145.8, 148.1 (C-Ar of quinoline),
162.4 (C-2 furan), 164.4 (3-C=O), 165.1 (4-C=O); m/z (EI, 70 eV) 486 (13, M+ [35Cl]), 488 (4,
M+ [37Cl]), 447 (4), 418 (3), 374 (79), 339 (43), 327 (4), 307 (30), 292 (4), 279 (10), 265 (2), 255
(17), 231 (2), 204 (33), 190 (6), 176 (23), 167 (9), 149 (13), 140 (15), 115 (11), 97 (13), 81 (16),
69 (33), 57 (100%).
4.2.10. Diethyl 2-(tert-butylamino)-5-(2-chloro-6-methylquinolin-3-yl)furan-3,4-dicarboxylate
(6j). Pale yellow solid (0.39 g, 85%), mp 128-130 °C; [Found: C, 63.11; H, 5.81; N, 6.18.
14

ACCEPTED MANUSCRIPT
C24H27ClN2O5 requires C, 62.81; H, 5.93; N, 6.10%]; Rf (20% EtOAc/hexane) 0.43; νmax (KBr)
3327 (NH), 1725 (C=O), 1661 (C=O) cm-1; δH (300 MHz, CDCl3) 1.19 (3H, t, J 7.1 Hz, 3-
OCH2Me), 1.30 (3H, t, J 7.1 Hz, 4-OCH2Me), 1.44 (9H, s, CMe3), 2.50 (3H, s, Me), 4.20 and
4.25 (4H, 2q, J 7.1, 7.1 Hz, 2OCH2Me), 6.98 (1H, br s, NH), 7.53-7.57 (2H, m, Ar), 7.89 (1H, d,
J 9.1 Hz, Ar), 8.20 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 21.5
(Me), 29.8 (CMe3), 52.8 (CMe3), 59.7 (3-OCH2Me), 61.3 (4-OCH2Me), 87.8 (C-3 of furan),
118.1 (C-4 of furan), 122.7 (C-5 of furan), 126.4, 126.6, 128.0, 133.5, 137.6, 138.8, 139.5, 145.7,
148.1 (C-Ar of quinoline), 162.4 (C-2 furan), 164.0 (3-C=O), 164.7 (4-C=O); m/z (EI, 70 eV)
458 (25, M+ [35Cl]), 460 (8, M+ [37Cl]), 413 (4), 402 (35), 367 (23), 356 (21), 339 (6), 327 (37),
310 (3), 393 (45), 282 (4), 265 (9), 255 (20), 221 (14), 204 (57), 176 (40), 167 (18), 149 (31),
140 (32), 115 (24), 97 (28), 81 (43), 69 (91), 57 (100%).
4.2.11. Diethyl 2-(2-chloro-6-methylquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-dicarboxylate
(6k). White solid (0.42 g, 87%), mp 193-195 °C; [Found: C, 64.79; H, 6.18; N, 5.82.
C26H29ClN2O6 requires C, 64.39; H, 6.03; N, 5.78%]; Rf (20% EtOAc/hexane) 0.41; νmax (KBr)
3358 (NH), 1752 (C=O), 1667 (C=O) cm-1; δH (300 MHz, CDCl3) 1.16-2.04 (16H, consisting
3H, t, J 7.1 Hz, 3-OCH2Me, 3H, t, J 7.1 Hz, 4-OCH2Me and 10H, m, 5CH2 of cyclohexyl), 2.52
(3H, s, Me), 3.65-3.67 (1H, m, CHNH of cyclohexyl), 4.23 (4H, two overlapped q, J 7.1 Hz,
2OCH2Me), 6.73 (1H, d, J 8.1 Hz, NH), 7.55-7.58 (2H, m, Ar), 7.90 (1H, d, J 8.5 Hz, Ar), 8.20
(1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.2 (4-OCH2Me), 21.6 (Me), 24.5 (2CH2),
25.4 (CH2), 33.4 (2CH2), 51.5 (CHNH of cyclohexyl), 59.7 (3-OCH2Me), 61.3 (4-OCH2Me),
86.8 (C-3 of furan), 118.3 (C-4 of furan), 122.7 (C-5 of furan), 126.4, 126.6, 128.0, 133.5, 137.6,
138.6, 139.5, 145.7, 148.3 (C-Ar of quinoline), 162.1 (C-2 furan), 163.8 (3-C=O), 164.7 (4-
C=O); m/z (EI, 70 eV) 484 (15, M+ [35Cl]), 486 (5, M+ [37Cl]), 401 (2), 367 (3), 356 (9), 339 (5),
15

ACCEPTED MANUSCRIPT
327 (9), 307 (4), 393 (11), 279 (3), 265 (3), 255 (8), 221 (4), 204 (32), 176 (17), 167 (9), 149
(21), 140 (13), 115 (13), 97 (22), 83 (39), 69 (52), 57 (100%).
4.2.12. Diethyl 2-(2-chloro-6-methylquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-
3,4-dicarboxylate (6l). White solid (0.47 g, 90%), mp 141-143 °C; [Found: C, 65.10; H, 7.18; N,
5.42. C28H35ClN2O5 requires C, 65.30; H, 6.85; N, 5.44%]; Rf (20% EtOAc/hexane) 0.50; νmax
(KBr) 3334 (NH), 1726 (C=O), 1661 (C=O) cm-1; δH (300 MHz, CDCl3) 1.01 (9H, s, CMe3),
1.89 (3H, t, J 7.1 Hz, 3-OCH2Me), 1.30 (3H, t, J 7.1 Hz, 4-OCH2Me), 1.49 (6H, s, CMe2), 1.77
(2H, s, CH2), 2.51 (3H, s, Me), 4.23 (4H, two overlapped q, J 7.1 Hz, 2OCH2Me), 7.09 (1H, br s,
NH), 7.56-7.58 (2H, m, Ar), 7.90 (1H, d, J 9.1 Hz, Ar), 8.20 (1H, s, Ar); δc (75 MHz, CDCl3)
14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 21.6 (Me), 30.1 (CMe2), 31.4 (CMe3), 31.7 (CMe3), 53.0
(CCH2C), 56.5 (CMe2), 59.7 (3-OCH2Me), 61.4 (4-OCH2Me), 87.5 (C-3 of furan), 118.2 (C-4 of
furan), 122.7 (C-5 of furan), 126.4, 126.6, 128.0, 133.5, 137.7, 138.6, 139.6, 145.7, 148.1 (C-Ar
of quinoline), 162.3 (C-2 furan), 164.0 (3-C=O), 164.8 (4-C=O); m/z (EI, 70 eV) 515 (13, M+
[35Cl]), 517 (4, M+ [37Cl]), 469 (2), 443 (3), 402 (53), 367 (28), 356 (20), 339 (6), 327 (24), 310
(2), 393 (35), 282 (4), 265 (9), 255 (13), 221 (7), 204 (32), 176 (20), 167 (10), 149 (10), 140
(13), 115 (9), 97 (11), 81 (12), 69 (28), 57 (100%).
4.2.13.
Dimethyl
2-(tert-butylamino)-5-(2-chloro-6-methoxyquinolin-3-yl)furan-3,4-
dicarboxylate (6m). Pale yellow solid (0.34 g, 76%), mp 174-176 °C; [Found: C, 59.12; H, 5.30;
N, 6.28. C22H23ClN2O6 requires C, 59.13; H, 5.19; N, 6.27%]; Rf (20% EtOAc/hexane) 0.31; νmax
(KBr) 3337 (NH), 1716 (C=O), 1670 (C=O) cm-1; δH (300 MHz, CDCl3) 1.45 (9H, s, CMe3),
3.74 (3H, s, 3-OMe), 3.78 (3H, s, 4-OMe), 3.90 (3H, s, OMe), 6.97 (1H, br s, NH), 7.07 (1H, d, J
16

ACCEPTED MANUSCRIPT
2.7 Hz, Ar), 7.37 (1H, dd, J 9.2, 2.7 Hz, Ar), 7.83 (1H, d, J 9.2 Hz, Ar), 7.17 (1H, s, Ar); δc (75
MHz, CDCl3) 29.8 (CMe3), 51.2 (3-OMe), 52.3 (4-OMe), 52.9 (CMe3), 55.6 (OMe), 87.6 (C-3
of furan), 105.2 (C-Ar of quinoline), 117.6 (C-4 of furan), 122.8 (C-5 of furan), 124.0, 127.5,
129.7, 138.8, 139.2, 143.2, 146.2, 158.5 (C-Ar of quinoline), 162.5 (C-2 furan), 164.4 (3-C=O),
165.1 (4-C=O); m/z (EI, 70 eV) 446 (32, M+ [35Cl]), 448 (11, M+ [37Cl]), 415 (4), 390 (23), 355
(91), 343 (4), 323 (60), 308 (4), 295 (24), 280 (2), 271 (21), 243 (8), 220 (34), 207 (7), 192 (28),
177 (8), 157 (14), 150 (6), 127 (6), 119 (13), 97 (7), 83 (8), 69 (11), 57 (100%).
4.2.14.
Dimethyl
2-(2-chloro-6-methoxyquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-
dicarboxylate (6n). Pale yellow solid (0.38 g, 80%), mp 212-214 °C; [Found: C, 60.97; H, 5.41;
N, 5.94. C24H25ClN2O6 requires C, 60.95; H, 5.33; N, 5.92%]; Rf (20% EtOAc/hexane) 0.23; νmax
(KBr) 3354 (NH), 1722 (C=O), 1667 (C=O) cm-1; δH (300 MHz, CDCl3) 1.36-2.03 (10 H, m,
5CH2 of cyclohexyl), 3.70-3.79 (7H consisting 3H, s, 3-OMe, 3H, s, 4-OMe and 1H, m, CHNH
of cyclohexyl), 3.91 (3H, s, OMe), 6.73 (1H, br d, J 5.5 Hz, NH), 7.08 (1H, s, Ar), 7.37 (1H, br
d, J 8.2 Hz, Ar), 7.90 (1H, br d, J 8.2 Hz, Ar), 8.17 (1H, s, Ar); δc (75 MHz, CDCl3) 24.5
(2CH2), 25.4 (CH2), 33.4 (2CH2), 51.1 (3-OMe), 51.5 (CHNH of cyclohexyl), 52.3 (4-OMe),
55.7 (OMe), 86.6 (C-3 of furan), 105.2 (C-Ar of quinoline), 117.8 (C-4 of furan), 122.8 (C-5 of
furan), 124.0, 127.5, 129.7, 138.8, 139.0, 143.2, 146.4, 158.5 (C-Ar of quinoline), 162.1 (C-2
furan), 164.2 (3-C=O), 165.0 (4-C=O); m/z (EI, 70 eV) 472 (31, M+ [35Cl]), 474 (10, M+ [37Cl]),
441 (2), 418 (8), 390 (3), 383 (17), 355 (27), 343 (7), 323 (32), 309 (11), 295 (11), 285 (6), 271
(14), 244 (6), 220 (57), 204 (7), 192 (32), 177 (11), 157 (31), 150 (31), 127 (13), 114 (17), 97
(20), 78 (92), 69 (29), 57 (100%).
17

ACCEPTED MANUSCRIPT
4.2.15. Dimethyl 2-(2-chloro-6-methoxyquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-
3,4-dicarboxylate (6o). Pale yellow solid (0.39 g, 78%), mp 158-160 °C; [Found: C, 60.76; H,
6.26; N, 5.29. C28H31ClN2O6 requires C, 62.08; H, 6.21; N, 5.57%]; Rf (20% EtOAc/hexane)
0.26; νmax (KBr) 3331 (NH), 1729 (C=O), 1668 (C=O) cm-1; δH (300 MHz, CDCl3) 1.01 (9H, s,
CMe3), 1.51 (6H, s, CMe2), 1.77 (2H, s, CH2), 3.75 (3H, s, 3-OMe), 3.79 (3H, s, 4-OMe), 3.92
(3H, s, OMe), 7.08 (1H, d, J 2.7 Hz, Ar), 7.10 (1H, br s, NH), 7.39 (1H, dd, J 9.2, 2.7 Hz, Ar),
7.91 (1H, d, J 9.2 Hz, Ar), 8.18 (1H, s, Ar); δc (75 MHz, CDCl3) 30.1 (CMe2), 31.4 (CMe3),
31.7 (CMe3), 51.2 (3-OMe), 52.4 (4-OMe), 53.0 (CCH2C), 55.7 (OMe), 56.5 (CMe2), 87.3 (C-3
of furan), 105.2 (C-Ar of quinoline), 117.7 (C-4 of furan), 122.9 (C-5 of furan), 124.0, 127.5,
129.7, 138.9, 138.9, 143.2, 146.3, 158.5 (C-Ar of quinoline), 162.3 (C-2 furan), 164.5 (3-C=O),
165.1 (4-C=O); m/z (EI, 70 eV) 502 (10, M+ [35Cl]), 504 (3, M+ [37Cl]), 446 (7), 418 (6), 390
(39), 355 (84), 343 (6), 323 (49), 309 (8), 295 (16), 280 (4), 271 (17), 243 (8), 220 (39), 207 (7),
192 (31), 178 (9), 157 (14), 149 (28), 127 (11), 111 (17), 97 (28), 81 (35), 69 (72), 57 (100%).
4.2.16. Diethyl 2-(tert-butylamino)-5-(2-chloro-6-methoxyquinolin-3-yl)furan-3,4-dicarboxylate
(6p). Pale yellow solid (0.35 g, 75%), mp 115-117 °C; [Found: C, 60.64; H, 5.86; N, 5.92.
C24H27ClN2O6 requires C, 60.69; H, 5.73; N, 5.90%]; Rf (20% EtOAc/hexane) 0.39; νmax (KBr)
3329 (NH), 1712 (C=O), 1666 (C=O) cm-1; δH (300 MHz, CDCl3) 1.21 (3H, t, J 7.1 Hz, 3-
OCH2Me), 1.32 (3H, t, J 7.1 Hz, 4-OCH2Me), 1.46 (9H, s, CMe3), 3.93 (3H, s, OMe), 4.22 and
4.26 (4H, 2q, J 7.1, 7.1 Hz, 2OCH2Me), 6.99 (1H, br s, NH), 7.07 (1H, d, J 2.7 Hz, Ar), 7.39
(1H, dd, J 9.2, 2.7 Hz, Ar), 7.92 (1H, d, J 9.2 Hz, Ar), 8.20 (1H, s, Ar); δc (75 MHz, CDCl3)
14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 29.8 (CMe3), 52.8 (CMe3), 55.7 (OMe), 59.8 (3-
OCH2Me), 61.4 (4-OCH2Me), 87.8 (C-3 of furan), 105.2 (C-Ar of quinoline), 118.1 (C-4 of
furan), 122.9 (C-5 of furan), 123.9, 127.5, 129.7, 138.7, 138.9, 143.2, 146.4, 158.5 (C-Ar of
18

ACCEPTED MANUSCRIPT
quinoline), 162.4 (C-2 furan), 164.1 (3-C=O), 164.7 (4-C=O); m/z (EI, 70 eV) 474 (36, M+
[35Cl]), 476 (12, M+ [37Cl]), 429 (18), 418 (18), 383 (78), 372 (13), 355 (10), 343 (31), 327 (2),
309 (81), 298 (3), 281 (13), 271 (18), 237 (9), 220 (50), 202 (16), 192 (39), 177 (12), 157 (31),
150 (13), 127 (17), 114 (5), 97 (17), 83 (17), 69 (25), 57 (100%).
4.2.17. Diethyl 2-(2-chloro-6-methoxyquinolin-3-yl)-5-(cyclohexylamino)furan-3,4-dicarboxylate
(6q). White solid (0.39 g, 78%), mp 195-197 °C; [Found: C, 62.45; H, 5.86; N, 5.61.
C26H29ClN2O6 requires C, 62.33; H, 5.83; N, 5.59%]; Rf (20% EtOAc/hexane) 0.32; νmax (KBr)
3362 (NH), 1725 (C=O), 1667 (C=O) cm-1; δH (300 MHz, CDCl3) 1.17-2.04 (16H consisting 3H,
t, J 6.9 Hz, 3-OCH2Me, 3H, t, J 6.9 Hz, 4-OCH2Me and 10H, m, 5CH2 of cyclohexy), 3.65-3.68
(1H, m, CHNH of cyclohexyl), 3.92 (3H, s, OMe), 4.24 (4H, two overlapped q, J 6.8 Hz,
2OCH2Me), 6.73 (1H, d, J 7.7 Hz, NH); 7.07 (1H, s, Ar), 7.38 (1H, d, J 9.0 Hz, Ar), 7.90 (1H, d,
J 9.0 Hz, Ar), 8.19 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 24.5
(2CH2), 25.4 (CH2), 33.4 (2CH2), 51.5 (CHNH of cyclohexyl), 55.7 (OMe), 59.7 (3-OCH2Me),
61.3 (4-OCH2Me), 86.9 (C-3 of furan), 105.2 (C-Ar of quinoline), 118.3 (C-4 of furan), 122.9
(C-5 of furan), 123.9, 127.5, 129.7, 138.6, 138.8, 143.1, 146.5, 158.5 (C-Ar of quinoline), 162.1
(C-2 furan), 163.9 (3-C=O), 164.6 (4-C=O); m/z (EI, 70 eV) 500 (24, M+ [35Cl]), 502 (8, M+
[37Cl]), 455 (2), 417 (2), 383 (9), 374 (28), 355 (6), 343 (12), 327 (10), 309 (23), 298 (3), 281
(5), 271 (8), 237 (6), 220 (31), 204 (14), 192 (19), 176 (10), 157 (9), 149 (9), 127 (9), 111 (14),
97 (24), 83 (40), 69 (52), 57 (100%).
4.2.18. Diethyl 2-(2-chloro-6-methoxyquinolin-3-yl)-5-(2,4,4-trimethylpentan-2-ylamino)furan-
3,4-dicarboxylate (6r). Pale yellow solid (0.43 g, 81%), mp 171-174 °C; [Found: C, 63.84; H,
19

ACCEPTED MANUSCRIPT
6.75; N, 5.42. C28H35ClN2O6 requires C, 63.33; H, 6.64; N, 6.68%]; Rf (20% EtOAc/hexane)
0.34; νmax (KBr) 3327 (NH), 1722 (C=O), 1661 (C=O) cm-1; δH (300 MHz, CDCl3) 1.02 (9H, s,
CMe3), 1.20 (3H, t, J 7.1 Hz, 3-OCH2Me), 1.32 (3H, t, J 7.1 Hz, 4-OCH2Me), 1.51 (6H, s,
CMe2), 1.78 (2H, s, CH2), 3.93 (3H, s, OMe), 4.22 and 4.26 (4H, 2q, J 7.1, 7.1 Hz, 2OCH2Me),
7.07 (1H, d, J 2.7 Hz, Ar), 7.10 (1H, br s, NH), 7.39 (1H, dd, J 9.2, 2.7 Hz, Ar), 7.92 (1H, d, J
9.2 Hz, Ar), 8.19 (1H, s, Ar); δc (75 MHz, CDCl3) 14.0 (3-OCH2Me), 14.4 (4-OCH2Me), 30.1
(CMe2), 31.4 (CMe3), 31.7 (CMe3), 53.0 (CCH2C), 55.7 (OMe), 56.5 (CMe2), 59.7 (3-OCH2Me),
61.4 (4-OCH2Me), 87.5 (C-3 of furan), 105.2 (C-Ar of quinoline), 118.2 (C-4 of furan), 123.0
(C-5 of furan), 123.9, 127.5, 129.7, 138.5, 138.9, 143.2, 146.4, 158.5 (C-Ar of quinoline), 162.3
(C-2 furan), 164.1 (3-C=O), 164.7 (4-C=O); m/z (EI, 70 eV) 531 (73, M+ [35Cl]), 533 (24, M+
[37Cl]), 485 (6), 459 (5), 418 (83), 383 (100), 372 (13), 355 (11), 343 (21), 327 (2), 309 (47), 298
(3), 282 (8), 271 (10), 237 (4), 220 (16), 204 (7), 192 (12), 177 (3), 157 (4), 57 (80%).
References
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Supporting Information
Three-component one-pot synthesis of quinoline-furan conjugates from
acetylenedicarboxylate, isocyanide, and 2-chloroquinoline-3-carbaldehyde
Mehdi Ghandi*, Nahid Zarezadeh
aSchool of Chemistry, College of Science, University of Tehran,
Tehran, P.O. Box 14155 6455, Iran
Content
Spectra (1H NMR and 13C NMR of all new compounds)
……………………….
2-37
* Corresponding author, Tel: +9821 61112250; fax: +9821 66495291;
e-mail address: ghandi@khayam.ut.ac.ir (M. Ghandi).
1

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O
O
O
O
O
N
O
Cl
6m
H
N
.
2

ACCEPTED MANUSCRIPT
O O
O
O
O
O
N
H
N
Cl
6r
3