Regioselective N-alkylation of (2-chloroquinolin-3-yl) methanol with N-heterocyclic compounds using the Mitsunobu reagent

Article abstract of DOI:10.2478/s11696-011-0018-1

The Mitsunobu reaction is a well-established fundamental reaction and has been widely applied in organic synthesis. In this paper, under Mitsunobu conditions dehydration proceeds between (2-chloroquinolin-3-yl)methanol and nitrogen heterocyclic compounds

Full text of DOI:10.2478/s11696-011-0018-1

Chemical Papers 65 (3) 345–351 (2011)
DOI: 10.2478/s11696-011-0018-1
ORIGINAL PAPER
Regioselective -alkylation of (2-chloroquinolin-3-yl) methanol
with -heterocyclic compounds using the Mitsunobu reagent
b
aSelvaraj Mohana Roopan, a,bFazlur-Rahman Nawaz Khan*, Jong Sung Jin*
aOrganic & Medicinal Chemistry Research Laboratory, Organic Chemistry Division, School of Advanced Sciences,
VIT University, Vellore, Tamil Nadu – 632 014, India
bDivision of High Technology Materials Research,
Busan Center, Korea Basic Science Institute (KBSI), Busan 618-230, Republic of Korea
Received 8 November 2010; Revised 4 January 2011; Accepted 7 January 2011
The Mitsunobu reaction is a well-established fundamental reaction and has been widely applied
in organic synthesis. In this paper, under Mitsunobu conditions dehydration proceeds between (2-
chloroquinolin-3-yl)methanol and nitrogen heterocyclic compounds such as quinazolinone, pyrimi-
done, 2-oxoquinoline in dry THF in the presence of triethylamine, triphenylphosphane and diethyl
azodicarboxylate to give the corresponding products. As part of our recent research, we attempted
to couple two N-heterocyclic compounds under Mitsunobu reaction conditions to provide efficient
building blocks for natural product synthesis.
c
ꢀ 2011 Institute of Chemistry, Slovak Academy of Sciences
Keywords: Mitsunobu reaction, N-heterocyclic compounds, (2-chloroquinolin-3-yl)methanol,
DEAD, P(Ph)3, THF
Introduction
cal activities. In the light of these findings, Mitsunobu
conditions have been utilised for the coupling of two
nitrogen heterocyclic compounds in our continued in-
terest in carbon-carbon and carbon-nitrogen bond for-
mation reaction (Patil et al., 2004; Roopan et al., 2008;
2009a, 2009b; 2010; Roopan & Khan, 2008; Manivel et
al., 2008), i.e. alkylation of a nucleophile (NuH) with
an alcohol in the presence of triphenylphosphane and
diethyl azodicarboxylate (DEAD). The reaction is a
highly regioselective process and proceeds under mild
conditions (essentially neutral and from 0◦C to room
temperature).
In connection with the design and synthesis of bio-
logically active and pharmacologically important new
building blocks, it was thought worthwhile to syn-
thesise compounds such as camptothecin (I ), map-
picine (II ), luotonin A (III ) (Fig. 1), and its analogues
(Das et al., 1998; Chavan & Sivappa, 2004a, 2004b;
Wang & Ganesan, 1998). Initially, the coupling of (2-
chloroquinolin-3-yl)methanol and its derivatives with
Heterocyclic compounds play important roles in
the drug discovery process, exhibit biological and
pharmacological properties of interest such as antibac-
terial and anti-cancer properties, inhibition of platelet
aggregation and HIV-1 protease (Kayser & Kolodziej,
1997; Wang et al., 2002; Cravotto et al., 2001; Kirki-
acharian et al., 2002). Analysis of drugs at a late stage
of their development or on the market shows that
68 % of drugs are heterocycles (Do¨mling & Ugi, 2000;
D¨omling, 2006). It is not surprising, therefore, that
research into the synthesis of heterocyclic compounds
has received significant attention. 2-Chloroquinoline
constitutes one of the most active compounds pos-
sessing diversified therapeutic activities (Kidwai et al.,
1997). A literature survey reveals that various quina-
zolinones, quinolines (Roopan et al., 2008; Guan et
al., 2007), etc., have attracted considerable attention
as they are also endowed with a wide range of biologi-
*Corresponding author, e-mail: nawaz f@yahoo.co.in; jsjin@kbsi.re.kr

346
S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
O
O
O
H3CO
N
N
N
O
O
N
N
N
N
HO
O
I
II
III
Fig. 1. Biologically active alkaloids: (I) camptothecin, (II) mappicine, and (III) luotonin A.
different heterocyclic compounds such as quinazoli-
none, pyrimidone, 2-oxoquinoline etc., using diethy-
lazodicarboxylate (DEAD) and triphenyl phosphane
(TPP) was attempted.
Prompted by recent observations in the liter-
ature and as a part of our search for bio-active
quinoline derivatives, we undertook the regioselective
coupling of (2-chloroquinolin-3-yl)methanol IV with
N-heterocyclic compounds V using the Mitsunobu
reagent.
characterised by FTIR, 1H NMR, 13C NMR, and
HRMS analyses.
Synthesis of 6-chloro-1-[(2-chloroquinolin-3-
yl)methyl]-2-oxo-4-phenyl-1,2-
dihydroquinoline-3-carboxylate (VIa)
To a mixture of (2-chloroquinolin-3-yl) methanol
IVa (12 mmol), ethyl 6-chloro-2-oxo-4-phenyl-1,2-
dihydroquinoline-3-carboxylate Va (10 mmol), P(Ph)3
(10 mmol), and (Et)3N (10 mmol) in THF (10 mL),
DEAD (10 mmol) were added drop-wise at 0◦C under
N2 atmosphere and stirred at room temperature for
23 h. The reaction mixture was then quenched with
5 % HCl and extracted with dichloromethane. The sol-
vent was evaporated and the residue purified by col-
umn chromatography providing ethyl-6-chloro-1-[(2-
chloroquinolin-3-yl)methyl]-2-oxo-4-phenyl-1,2-dihyd-
roquinoline-3-carboxylate VIa as a white solid.
Experimental
The chemical reagents and all solvents used in this
study were purchased from Aldrich Chemicals and
S.D. Fine chemicals (India). The N-heterocycles such
as IVa–IVd, Va, Vb, and VIII required for this study
were prepared by the reported procedure (Roopan et
al., 2008; Roopan & Khan, 2009, 2010; Khan et al.,
2009a–2009e, 2010a, 2010b; Leonard & Curtin, 1946;
Alexandre et al., 2003). The compounds were pre-
pared, analysed, and compared with data from the
literature. Melting points were determined in an open
capillary tube and corrected using standard benzoic
acid. IR spectra were obtained on a Nucon Infrared
spectrophotometer (India) (KBr disc). NMR spectra
were recorded on a Bruker 500 spectrometer (India)
and chemical shifts are reported in parts per million
(δ) relative to tetramethylsilane (TMS) as an internal
standard.
Synthesis of 3-((2-chloro-7,8-dimethylquinolin-
3-yl)methyl)quinazoline-4(3H)-thione (VII)
A solution of 3-[(2-chloro-7,8-dimethylquinolin-3-
yl)methyl]quinazolin-4(3H)-one VId (1 mmol), and
the Lawessons’s reagent (2,4-bis(4-methoxyphenyl)-
1,3,2,4-dithiadiphosphetane-2,4-disulphide) (0.8 mmol)
in dry THF was refluxed until the reaction was com-
pleted. Completion of the reaction was monitored by
TLC. The excess solvent was removed under reduced
pressure. The residue was then poured into cooled wa-
ter and filtered off. Obtained yellow solid was then
subjected to column chromatography using hexane
and ethylacetate (ϕr = 9 : 1).
Coupling of N-heterocyclic compounds (VIa–
VIf)
To the solution of triphenylphosphane (10 mmol)
and triethylamine (10 mmol) in dry THF (10 mL), nu-
cleophile V (10 mmol), (2-chloroquinolin-3-yl)methan-
ol IV (12 mmol) were well mixed under a nitrogen at-
mosphere and cooled to 0◦C; then, DEAD (10 mmol)
was added drop-wise. The reaction mixture was al-
lowed to warm to room temperature and stirred at
that temperature until the reaction proceeded to com-
pletion as confirmed by TLC. The reaction mixture
was quenched with 5 % HCl (10 mL) and extracted
with dichloromethane, concentrated on a rotary evap-
orator. The crude product was purified on silica gel
using column chromatography. All the products were
Synthesis of 4-[(2-chloro-7,8-dimethylquinolin-
3-yl)methylthio]quinazoline (IX)
To an equimolar mixture of (2-chloro-7,8-dimethyl-
quinolin-3-yl) methanol IVb and quinazoline-4(3H)-
thione VIII, P(Ph)3, and (Et)3N in THF (2 mL),
DEAD was added drop-wise at 0◦C under N2 at-
mosphere and stirred at room temperature for 10
h. The reaction was then quenched with 5 % HCl
and the mixture extracted with ethylacetate. The sol-
vent was evaporated and the residue purified by col-
umn chromatography provided ethyl 4-[(2-chloro-7,8-

S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
347
Table 1. Mitsunobu alkylation of N-heterocyclic compounds
(quinolin-2(1H )-one, 4(3H )-pyrimidone, quinazolin-
4(3H )-one)
Data of known compounds VIa, VIe, and VIf are iden-
tical with the data in our earlier reports (Roopan &
Khan, 2010; Roopan et al., 2010).
While employing traditional addition–elimination
chemistry involving alcohol IV with nucleophile V
we were intrigued by the possible application of the
Mitsunobu reaction to construct our desired C—N
bond and furnish the coupled products VI. The syn-
thesis route leading to the coupled compounds is
summarised in Table 1. When (2-chloroquinolin-3-
yl)methanol IV and various nucleophiles were sub-
jected to the Mitsunobu reaction, the corresponding
coupled product was obtained in lower yields after a
long reaction time. We carried out the same reaction
in the presence of an equivalent of triethylamine and
obtained a high yield after 48 h. The synthesis route
uses milder reaction conditions, can be carried out in
fewer steps, requires less time and provides excellent
yields.
Compound
Substrates
M.p./◦C
Yielda/%
VIab
VIb
VIc
VId
VIec
VIf c
IVa
Va
Va
Vb
Vb
Vc
Vc
202
126
188
192
158
187
54
62
67
45
52
55
IVb
IVa
IVc
IVa
IVd
a) Isolated yield; b) reported in Roopan and Khan (2010); c)
reported in Roopan et al. (2010).
dimethylquinolin-3-yl)methylthio]quinazoline IX as a
white solid.
Results and discussion
The Mitsunobu reaction involves a triphenyl-
phosphane–azodicarboxylate adduct illustrated in
Fig. 3. The nucleophilic addition of alcohol IV to phos-
Data for new compounds VIb–VId, VII, and IX
which were not reported earlier are given in Table 2.
Table 2. Spectral data of newly prepared compounds
Compound
Spectral data
VIb
VIc
IR, ν˜/cm−1: 1730 (C O)
—
—
1H NMR (400 MHz, CDCl3), δ: 8.34 (s, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.68 (d, J = 6.4 Hz, 1H), 7.64–7.61 (m, 1H),
7.58 (d, J = 5.2 Hz, 1H), 7.54–7.51 (m, 4H), 7.46 (t, 1H), 7.42–7.41 (m, 2H), 5.88 (s, 2H), 4.18–4.14 (q, 2H), 2.90
(s, 3H), 1.03 (t, 3H)
13C NMR (100 MHz, CDCl3), δ: 165.5, 156.8, 148.2, 148.0, 146.2, 144.7, 137.1, 136.4, 134.3, 131.1, 130.5, 130.3,
129.1, 2 × 129.0, 2 × 128.8, 128.5, 128.4, 127.1, 2 × 126.7, 125.4, 124.9, 119.6, 64.4, 61.4, 17.7, 13.6
HRMS, m/z (found/calc.): 517.7798/517.4026 (M+, C29H22Cl2N2O3)
IR, ν˜/cm−1: 1675 (C O)
—
—
1H NMR (300 MHz, CDCl3), δ: 8.57 (s, 1H), 8.16 (dd, J = 6.4 Hz, J = 7.9 Hz, 2H), 7.98 (dd, J = 8.1 Hz, J = 8.4
Hz, 2H), 7.87 (dd, J = 8.2 Hz, J = 7.0 Hz, 1H), 7.77 (dd, J = 7.0 Hz, J = 8.2 Hz, 2H), 7.63–7.54 (m, 2H), 5.39 (s,
2H)
13C NMR (75 MHz, CDCl3), δ: 160.7, 148.9, 148.7, 148.5, 146.6, 137.6, 135.0, 131.3, 128.57, 128.52, 127.99, 127.91,
127.85, 127.7, 127.3, 126.6, 122.2, 47.71
LCMS, m/z (Ir): 322 (M+ + 1)
HRMS, m/z (found/calc.): 321.6867/321.7604 (M+, C18H12ClN3O)
—
VId
VII
IX
IR, ν˜/cm−1: 1685 (C O)
—
1H NMR (500 MHz, CDCl3), δ: 8.34 (d, J = 5.5 Hz, 1H), 8.31 (d, 1H), 8.13 (s, 1H), 7.81–7.75 (m, 2H), 7.53 (dd, J
= 8.0 Hz, J = 5.5 Hz, 2H), 7.37 (d, J = 8.5 Hz, 1H), 5.41 (s, 2H), 2.69 (s, 3H), 2.49 (s, 3H)
13C NMR (100 MHz, CDCl3), δ: 161.2, 148.1, 148.0, 146.5, 139.5, 139.1, 134.5, 133.8, 2 × 130.3, 127.6, 127.5, 126.8,
125.4, 125.2, 124.6, 122.1, 47.7, 20.7, 13.3
HRMS, m/z (found/calc.): 349.4183/349.8135 (M+, C20H16ClN3O)
IR, ν˜/cm−1: 1110 (C S)
—
—
1H NMR (400 MHz, CDCl3), δ: 8.82 (s, 1H), 8.28 (d, J = 6.4 Hz, 1H), 8.08 (s, 1H), 7.75 (d, J = 4.8 Hz, 2H),
7.50–7.44 (m, 2H), 7.18 (d, J = 6.8 Hz, 1H), 5.44 (s, 2H), 2.45–2.43 (s, 6H, 2 × CH3)
13C NMR (125 MHz, CDCl3), δ: 180.9, 161.6, 148.0, 147.9, 141.0, 138.0, 137.3, 134.3, 132.2, 2 × 127.4, 127.1, 126.5,
126.0, 122.2, 121.0, 120.2, 49.6, 20.9, 12.1
HRMS, m/z (found/calc.): 365.3989/365.0753 (M+, C20H16ClN3S)
IR, ν˜/cm−1: 1616
1H NMR (400 MHz, CDCl3), δ: 9.08 (s, 1H), 8.36 (s, 1H), 8.11 (d, J = 6.8 Hz, 1H), 8.00 (d, J = 6.8 Hz, 1H), 7.88
(t, 1H), 7.61 (t, 1H), 7.54 (d, J = 6.8 Hz, 1H), 7.37 (d, J = 6.8 Hz, 1H), 4.91 (s, 2H), 2.71 (s, 3H, CH3), 2.50 (s,
3H, CH3)
13C NMR (125 MHz, CDCl3), δ: 149.7, 146.2, 139.2, 138.5, 133.9, 133.7, 130.0, 128.7, 127.6, 127.5, 125.5, 124.3,
123.8, 31.0, 20.7, 13.3
HRMS, m/z (found/calc.): 365.8989/365.0753 (M+, C20H16ClN3S)

348
S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
OH
OH
OH
O
N
Cl
N
Cl
H3C
HN
N
Cl
CH3
CH3
IVc
IVb
IVa
O
OEt
O
N
H3C
OH
O
HN
HN
N
Cl
Ph
N
IVd
Vc
Va
Vb
Cl
Fig. 2. Substrates VIa–VId used in Mitsunobu alkylation of VIa–VIc.
O
O
H
N
O
O
N
O
O
O
N
H
O
N
P(Ph)3=O
O
P(Ph)3
O
+
+
PPh3
H
N
O
OEt Ph
O
N
Cl
N
a
Cl
O
PPh3O
O
O
O
N
N
EtO
Ph
N
OH
Cl
N
Cl
Cl
VIb
IVb
Va
Fig. 3. Reaction mechanism of the synthesis of compound VI.
phonium ion gives the intermediate a (Fig. 3). Taking
the proposed Mitsunobu reaction into consideration,
the mechanism proceeds through an intermediate in-
volving carboxylic amide Va.
We believe that the formation of ethyl 6-chloro-1-
[(2-chloro-8-methylquinolin-3-yl)methyl]-2-oxo-4-
phenyl-1,2-dihydroquinoline-3-carboxylate VIb from
(2-chloroquinolin-3-yl)methanol IVa and ethyl 6-
chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carb-
oxylate Va under Mitsunobu conditions results in a
good yield.
peak singlet around δ 12.4 which corresponds to the
NH proton, whereas compound VIb showed an absence
of the absorption band due to NH stretching frequency
in the IR spectrum and NH peak in NMR; the sig-
nals due to protons of (2-chloro-8-methylquinolin-3-
yl)methyl moiety seen as a singlet at δ 5.88 clearly in-
dicated the formation of VIb. The remaining aromatic
protons appeared as a complex multiplet in the region
of δ 7.25–8.36 integrating thirteen protons. Similarly,
in all cases, the disappearance of the NH peak con-
firms the formation of products VIa–VIf.
Compound VIb was characterised by spectral
The 1H NMR spectra of the synthesised VIa–VIf in
CDCl3 are listed (see Table 2, for other compound see
Roopan and Khan (2010) and Roopan et al. (2010)).
Inspection of the HSQC spectrum of VIb (Fig. 4) re-
veals that correlation of the chemical shifts of the di-
1
(FTIR, H NMR, 13C NMR) data and HRMS anal-
ysis. Significant changes are observed in the IR
and NMR spectra of ethyl 6-chloro-1-[(2-chloro-8-
methylquinolin-3-yl)methyl]-2-oxo-4-phenyl-1,2-di-
hydroquinoline-3-carboxylate VIb as compared with
ethyl 6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-
1
rectly bound nuclei H and 13C exists. In compound
VIb, bridged methylene protons appear in downfield
region δ 5.88 whereas in IVb (Roopan & Khan, 2010)
methylene protons appeared at δ 4.92, due to the pres-
—
carboxylate Va. Compound Va exhibits νmax(C O)
—
peaks at 1663 cm−1 and in the 1H NMR spectrum

S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
349
A
B
Fig. 4. HSQC of VIb (A) and its detailed view (B).
O
N
N
VId
N
Cl
Lawessons reagent
THF, reflux, 1 h
S
N
VII
N
N
Cl
N
S
N
P(Ph)3, DEAD
(Et)3N, THF
S
N
Cl
IX
OH
HN
+
N
Cl
N
IVb
VIII
Fig. 5. Synthesis of 3-[(2-chloro-7,8-dimethylquinolin-3-yl)methyl]quinazolin-4(3H )-thione, VII.
ence of chlorine which decreased the electron density
of the phenyl ring in compound VIb. So the methy-
lene proton shifted to the downfield region. However,
in compound VIe, bridged methylene protons appear
in the upfield region of δ 4.84 due to the electron-
donating nature of nitrogen (pyrimidine ring) present
in the ring. When compared with the VIe compound,
VIc appeared upfield due to fusion of the benzene ring
with the pyridine moiety which decreased the electron
density.
occurred on the nitrogen atom and not on the oxygen
atom, more reactions were carried out (Fig. 5). The
alkylated product, VId was treated with Lawesson’s
reagent in the presence of dry THF and offered the
thionated product, 3-[(2-chloro-7,8-dimethylquinolin-
3-yl)methyl]quinazolin-4(3H)-thione VII, which sug-
gested a free carbonyl group inVId and hence a free
oxygen atom. Similarly, when the starting material
quinazolin-4(3H)-one V was thionated to the corre-
sponding thioderivative VII and then alkylated with
(2-chloro-7,7-dimethylquinolin-3-yl)methanol IVb it
In order to confirm that the regioselective coupling

350
S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
provided the thioether, 4-(2-chloro-7,8-dimethylquino-
lin-3-yl)methylthio)quinazoline IX and not the thion-
ated N-alkylated product VII. The above reactions
confirm the regioselective N-alkylation.
Khan, F. N., Roopan, S. M., Hathwar, V. R., & Ng, S.
W. (2010b). 2-Chloro-3-hydroxymethyl-6-methoxyquinoline.
Acta Crystallographica Section E, E66, o201. DOI: 10.1107/
S1600536809054051.
Khan, F. N., Subashini, R., Kumar, R., Hathwar, V. R., & Ng, S.
W. (2009b). 2-Chloroquinoline-3-carbaldehyde. Acta Crystal-
lographica Section E, E65, o2710. DOI: 10.1107/S160053680
9040665.
Conclusions
Khan, F. N., Subashini, R., Kushwaha, A. K., Hathwar, V.
The regioselective coupling of N-heterocyclic com-
pounds VI under Mitsunobu conditions provided the
corresponding products in moderate to good yields
from (2-chloroquinolin-3-yl)methanol IV and various
nucleophiles V in the presence of a mild and efficient
base catalyst, (Et)3N.
R.,
& Ng, S. W. (2009c). 2-Chloro-8-methylquinoline-3-
carbaldehyde. Acta Crystallographica Section E, E65, o2722.
DOI: 10.1107/S1600536809040859.
Khan, F. N., Subashini, R., Kushwaha, A. K., Hathwar, V.
R., & Ng, S. W. (2009d). 2-Chloro-7,8-dimethylquinoline-3-
carbaldehyde. Acta Crystallographica Section E, E65, o2709.
DOI: 10.1107/S1600536809040860.
Acknowledgements. The authors gratefully acknowledge fi-
nancial support from the Department of Science and Technol-
ogy, Government of India (Grant No. SR/FTP/CS-99/2006).
The authors are grateful to the VIT University management
for their generous support and facilities. We also acknowledge
SAIF, IIT Madras, Chennai for providing NMR and MS facil-
ity.
Khan, F. N., Subashini, R., Roopan, S. M., Hathwar, V.
R.,
& Ng, S. W. (2009e). 2-Chloro-6-methylquinoline-3-
carbaldehyde. Acta Crystallographica Section E, E65, o2686.
DOI: 10.1107/S1600536809040653.
Kidwai, M., & Negi, N. (1997). Synthesis of some novel substi-
tuted quinolines as potent analgesic agents. Monatshefte fu¨r
Chemie, 128, 85–89. DOI: 10.1007/BF00807642.
Kirkiacharian, S., Thuy, D. T., Sicsic, S., Bakhchinian, R.,
Kurkjian, R., & Tonnaire, T. (2002). Structure–activity
relationships of some 3-substituted-4-hydroxycoumarins as
HIV-1 protease inhibitors. Il Farmaco, 57, 703–708. DOI:
10.1016/S0014-827X(02)01264-8.
Leonard, N. J., & Curtin, D. Y. (1946). Preparation of 4-
mercapto and 4-amino quinazolines. The Journal of Organic
Chemistry, 11, 349–352. DOI: 10.1021/jo01174a007.
Manivel, P., Roopan, S. M., & Khan, F. N. (2008). Syn-
thesis of O-substituted benzophenones by Grignard reac-
tion of 3-substituted isocoumarins. Journal of the Chilean
Chemical Society, 53, 1609–1610. DOI: 10.4067/S0717-
97072008000300012.
References
Alexandre, F. R., Berecibar, A., Wrigglesworth, R., & Besson,
T. (2003). Novel series of 8H-quinazolino[4,3-b]quinazolin-8-
ones via two Niementowski condensations. Tetrahedron, 59,
1413–1419. DOI: 10.1016/S0040-4020(03)00053-X.
Chavan, S. P., & Sivappa, R. (2004a). A short and efficient
general synthesis of luotonin A, B and E. Tetrahedron, 60,
9931–9935. DOI: 10.1016/j.tet.2004.08.025.
Chavan, S. P., & Sivappa, R. (2004b). A synthesis of camp-
tothecin. Tetrahedron Letters, 45, 3113–3115. DOI: 10.1016/
j.tetlet.2004.02.091.
Cravotto, G., Nano, G. M., Palmisano, G., & Tagliapietra, S.
(2001). An asymmetric approach to coumarin anticoagulants
via hetero-Diels–Alder cycloaddition. Tetrahedron: Asymme-
try, 12, 707–709. DOI: 10.1016/S0957-4166(01)00124-0.
Das, B., Madhusudhan, P., & Kashinatham, A. (1998). Two
efficient methods for the conversion of camptothecin to map-
picine ketone, an antiviral lead compound. Tetrahedron Let-
ters, 39, 431–432. DOI: 10.1016/S0040-4039(97)10539-1.
D¨omling, A. (2006). Recent developments in isocyanide based
multicomponent reactions in applied chemistry. Chemical
Reviews, 106, 17–89. DOI: 10.1021/cr0505728.
Patil, N. T., Khan, F. N., & Yamamoto, Y. (2004). Microwave-
enhanced Pd(0)/acetic acid catalyzed allylation reactions of
C, N, and O-pronucleophiles with alkynes. Tetrahedron Let-
ters, 45, 8497–8499. DOI: 10.1016/j.tetlet.2004.09.099.
Roopan, S. M., Hathwar, V. R., Kumar, A. S., Malathi, N., &
Khan, F. N. (2009a). N-phenylnictoninamide. Acta Crystal-
lographica Section E, E65, o571. DOI: 10.1107/S160053680
9004863.
Roopan, S. M., & Khan, F. R. N. (2010). ZnO nanoparticles in
the synthesis of some AB ring core of camptothecin. Chemi-
cal Papers, 64, 812–817. DOI: 10.2478/s11696-010-0058-y.
Roopan, S. M., & Khan, F. R. N. (2009). Synthesis, antioxi-
dant, hemolytic and cytotoxicity activity of AB ring cores of
mappicine. ARKIVOC, xiii, 161–169.
D¨omling, A., & Ugi, I. (2000). Multicomponent reactions with
isocyanides. Angewandte Chemie International Edition, 39,
3168–3210. DOI: 10.1002/1521-3773(20000915)39:18<3168::
AID-ANIE3168>3.0.CO;2-U.
Roopan, S. M., & Khan, F. N. (2008). Free radical scavenging
activity of nitrogen heterocyclics–quinazolinones & tetrahy-
drocarbazolones. Indian Journal of Heterocyclic Chemistry,
18, 183–184.
Roopan, S. M., Khan, F. R. N., & Mandal, B. K. (2010). Fe
nanoparticles mediated C–N bond-forming reaction: Regios-
elective synthesis of 3-[(2-chloroquinolin-3-yl)methyl]pyrimi-
din-4(3H )-ones. Tetrahedron Letters, 51, 2309–2311. DOI:
10.1016/j.tetlet.2010.02.128.
Guan, L.-P., Jin, Q.-H., Tian, G.-R., Chai, K.-Y., & Quan, Z.-
S. (2007). Synthesis of some quinoline-2(1H)-one and 1,2,4-
triazolo [4,3-a] quinoline derivatives as potent anticonvul-
sants. Journal of Pharmacy & Pharmaceutical Sciences, 10,
254–262.
Kayser, O., & Kolodziej, H. (1997). Antibacterial activity
of extracts and constituents of Pelargonium sidoides and
Pelargonium reniforme. Planta Medica, 63, 508–510. DOI:
10.1055/s-2006-957752.
Roopan, S. M., Maiyalagan, T.,
& Khan, F. N. (2008).
Khan, F. N., Mittal, S., Anjum, S., Hathwar, V. R., & Ng, S. W.
(2009a). Ethyl 6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-
3-carboxylate. Acta Crystallographica Section E, E65, o2987.
DOI: 10.1107/S1600536809045425.
Solvent-free syntheses of some quinazolin-4(3H)-ones deriva-
tives. Canadian Journal of Chemistry, 86, 1019–1025. DOI:
10.1139/V08-149.
Roopan, S. M., Reddy, B. R., Kumar, A. S., & Khan, F. N.
(2009b). Synthesis of 3-substituted isocoumarins using mont-
morillonite K-10. Indian Journal of Heterocyclic Chemistry,
19, 81–82.
Khan, F. N., Roopan, S. M., Hathwar, V. R., & Ng, S. W.
(2010a). 2-Chloro-3-hydroxymethyl-7,8-dimethylquinoline.
Acta Crystallographica Section E, E66, o200. DOI: 10.1107/
S160053680905404X.

S. M. Roopan et al./Chemical Papers 65 (3) 345–351 (2011)
351
Wang, C.-J., Hsieh, Y.-J., Chu, C.-Y., Lin, Y.-L., & Tseng, T.-H.
(2002). Inhibition of cell cycle progression in human leukemia
HL-60 cells by esculetin. Cancer Letters, 183, 163–168. DOI:
10.1016/S0304-3835(02)00031-9.
Wang, H., & Ganesan, A. (1998). Total synthesis of the cyto-
toxic alkaloid luotonin ATetrahedron Letters, 39, 9097–9098.
DOI: 10.1016/S0040-4039(98)02004-8.