Synthesis of 2-alkynylquinolines from 2-chloro and 2,4-dichloroquinoline via Pd/C-catalyzed coupling reaction in water

Article abstract of DOI:10.1016/j.tet.2008.05.097

The Pd/C-CuI-PPh₃ catalyst system facilitated Sonogashira coupling of 2-chloroquinoline and 2,4-dichloroquinoline with terminal alkynes in water without generating any significant side products. A variety of 2-alkynylquinolines were prepared from 2-chloroquinoline in good to excellent yields and the 2,4-dichloroquinoline afforded monosubstituted product i.e., 2-alkynyl-4-chloro quinoline with high regioselectivity. The methodology was found to be effective for the alkynylation of 1-chloroisoquinoline and 3-methyl-2-chloroquinoline.

Full text of DOI:10.1016/j.tet.2008.05.097

Tetrahedron 64 (2008) 7143–7150
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of 2-alkynylquinolines from 2-chloro and 2,4-dichloroquinoline
via Pd/C-catalyzed coupling reaction in water
,
,
*
Ellanki Amarender Reddya b, Deepak Kumar Barange a, Aminul Islam a, K. Mukkanti b, Manojit Pal a
a Dr. Reddy’s Laboratories Limited, Bollaram Road, Miyapur, Hyderabad 500049, Andhra Pradesh, India
b Chemistry Division, Institute of Science and Technology, JNT University, Kukutpally, Hyderabad 500072, Andhra Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The Pd/C–CuI–PPh3 catalyst system facilitated Sonogashira coupling of 2-chloroquinoline and 2,4-di-
chloroquinoline with terminal alkynes in water without generating any significant side products. A va-
riety of 2-alkynylquinolines were prepared from 2-chloroquinoline in good to excellent yields and the
2,4-dichloroquinoline afforded monosubstituted product i.e., 2-alkynyl-4-chloro quinoline with high
regioselectivity. The methodology was found to be effective for the alkynylation of 1-chloroisoquinoline
and 3-methyl-2-chloroquinoline.
Received 16 February 2008
Received in revised form 21 May 2008
Accepted 22 May 2008
Available online 24 May 2008
Keywords:
2-Chloroquinoline
Alkyne
Ó 2008 Elsevier Ltd. All rights reserved.
Catalysis
Palladium
Water
1. Introduction
particular, synthetic strategies based on C–C bond formation via
transition metal-catalyzed alkynylation of 2-haloquinolines as
Since the discovery of Cinchona alkaloids as anti-malarial agents
the quinoline ( -electron deficient heterocycle) core has become
a key synthetic step (Fig. 2) have attracted considerable attention,
owing to the excellent levels of selectivity and high functional
group compatibility. Thus Sonogashira coupling7 (alkynylation of
aryl/heteroaryl halides) or its modified form has been used suc-
cessfully for the preparation of a variety of 2-alkynylquinolines.1c,8,9
However, the main disadvantage of all these methods is that the
Pd-catalysts used are destroyed in the work-up procedure and
cannot be recovered or reused. Therefore, development of im-
proved and flexible synthetic methods for accessing existing and
novel quinoline derivatives is in great demand mainly because of
the increasing resistance of malarial parasites in the use of chlo-
roquine (a widely used anti-malarial drug)1b requires a convenient
access to its appropriate analogs. Recently, we have reported Pd/C–
p
one of the privileged structures for the design and development of
potential new drugs. Substituted quinolines display a wide range of
pharmacological activities.1,2 For example, a number of naturally
occurring 2-substituted quinoline derivatives have been reported
to be highly effective against leishmaniasis, a widespread parasitic
disease caused by protozoan parasites of the genus Leishmania in
tropical and subtropical areas in both the old and the new worlds.3
These include mainly 2-alkyl substituted quinolines A–F (Fig. 1),
e.g., chimanine (D), cusparine (E), etc., and can be extracted from
a plant of the genus Galipea or may be synthesized chemically by
using dialkylquinolylboranes.4 Recently, 2-alkenyl/alkynylquino-
lines were reported to have anti-retroviral properties5 and the
presence of unsaturation at the C-2 position of the quinoline ring
seemed to play an important role in their pharmacological
activities.
R'
In view of their remarkable biological importance, many efforts
have been devoted to the development of new synthetic method-
ologies for the preparation of 2-substituted quinolines.6 In
N
R
A; R = 3,4-methylenedioxyphenylethyl, R' = H
B; R = methyl,R' = H
C; R = n-propyl, R' = OMe
D; R = methyl,R' = OMe (chimanine)
E; R = 3,4-methylenedioxyphenyl, R' = OMe (cusparine)
F; R = 3,4-dimethoxyphenyl, R' = H
* Corresponding author at present address: New Drug Discovery, R&D Center,
Matrix Laboratories Limited, Anrich Industrial Estate, Bollaram, Jinnaram Mandal,
Medak District 502 325, Andhra Pradesh, India. Tel.: þ91 08458 279301x2005; fax:
þ91 08458 279305.
Figure 1. Structures of some 2-substituted quinoline alkaloids isolated from Galipea
E-mail address: manojitpal@rediffmail.com (M. Pal).
species.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.097

7144
E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
Table 1
R'
R'
N
R'
N
Effect of solvents on the coupling reaction of 2-chloroquinoline (1) with 2-methyl
but-3-yn-2-ola (2a)
R
+
N
X
Entry
Solvent
Time (h)
Yieldb (%)
R
R
1
2
3
4
5
6
7
DMF
DMF
THF
MeCN
Dioxane
H2O
5
10
10
10
10
10
10
67
83
76
72
70
87
51c
Figure 2. Synthetic strategy for the preparation of 2-alkyl quinolines.
Cu mediated alkynylation of several chloro derivatives where the
chloro group was part of –Z]C(Cl)– moiety [Z¼N or C] in DMF.10 On
the other hand, we have observed that Pd/C–Cu mediated alkyny-
lation of bromo and iodo arenes/heteroarenes proceed smoothly in
water.11 Inspired by these results and due to our longstanding in-
terest in the synthesis of quinoline derivatives12 of potential
pharmacological significance, we chose to investigate the coupling
of a wide array of terminal alkynes with 2-chloroquinoline in water
using air and moisture stable 10% Pd/C as a key catalyst. Herein, we
report first one step efficient synthesis of 2-alkynylquinolines
starting from readily available starting materials under mild con-
ditions using 10% Pd/C–CuI–PPh3 as a catalyst system in water.
H2O
a
All the reactions were carried out by using 1 (1.0 equiv), 2a (1.5 equiv), 10% Pd/C
(0.026 equiv), PPh3 (0.20 equiv), CuI (0.05 equiv), and Et3N (3 equiv) at 80 ꢀC.
b
Isolated yields.
2-Aminoethanol was used in place of Et3N.
c
aminoethanol as a base in place of triethylamine resulted in
a mixture of products perhaps due to its direct reaction with 1
thereby lowering the yield of 3a (entry 7, Table 1). To determine the
reusability of the recovered Pd/C-catalyst the reaction mixture of 1
and 2a (entry 6, Table 1) was allowed to cool to room temperature.
After filtration, washing with water, acetone, and DCM, and drying,
the catalyst was used to conduct the reaction of 1 with 2a in the
presence of same reagents, base, ligand, and cocatalyst. The process
was repeated for two times when 95 and 80% conversions were
observed. Since cheaply available Pd/C and water were found to be
highly effective, reusable catalyst and solvent, respectively, for the
Sonogashira coupling of 2-chloroquinoline with terminal alkyne
hence we decided to test the generality and scope of this protocol
for the preparation of 2-alkynylquinolines. Thus, a variety of com-
mercially available terminal alkynes were employed under the re-
action condition studied and results are summarized in Table 2.
As outlined in Table 2, 2-chloroquinoline (1) showed good re-
activity toward the present coupling reaction in water (entries 1–
18, Table 1). Various functional groups including hydrophilic and
hydrophobic substitutents, for example, hydroxy, alkyl, cyano,
chloro, aryl, etc., present in the terminal alkynes were well toler-
ated. This allowed the preparation of a wide variety of 2-alky-
nylquinolines (3a–q) under mild condition in good to excellent
yields. It is worthy to mention that like our earlier observation11 the
present coupling reaction in water was also found to be selective
and no significant dimerization of terminal alkynes was observed
except when arylalkynes (3m–p) were used. To test the applica-
bility of this protocol for the preparation of quinoline derivatives of
biological interest we then used 2,4-dichloroquinoline17 for the
coupling reaction with terminal alkyne. When treated with 1-
octyne (2j) under the condition studied, 2,4-dichloroquinoline (4)
afforded monosubstituted product i.e., 2-alkynylquinoline de-
rivative (5) with high regioselectivity (Scheme 3). While regiose-
lective Sonogashira coupling of 2,4-dihaloquinolines was mainly
performed by using different halides such as iodide and bromide,18a
2,4-dibromoquinolines, however, showed a similar regioselectivity
by providing the C-2 alkynylated product when reacted with
terminal alkynes.8a Depending on the target compound to be
synthesized, the C-4 chloro group of compound 5 can be functio-
nalized18b–d further after reduction of the acetylenic moiety8a
to provide the compound of biological interest. Compound
2b showed nematocidal and trichomonacidal activities when
tested in vitro against the nematodes Caenorhabditis elegans,
2. Results and discussion
To assess the feasibility of this strategy, the 2-chloroquinoline
(1) we have chosen as a key precursor due to the high reactivity of
its C-2 chlorine toward nucleophiles14 in the absence or presence of
transition metal catalysts15,16 (path a or path b, Scheme 1). Ac-
cordingly, 2-chloroquinoline (1) was treated with terminal alkynes
(2, R¼alkyl, hydroxyalkyl, aryl, etc.) in water in the presence of 10%
Pd/C (0.026 equiv), PPh3 (0.20 equiv), CuI (0.05 equiv), and tri-
ethylamine (3 equiv) under nitrogen. The reaction proceeded well
to give 2-alkynylquinolines (3) in good to excellent yields via C–C
bond formation (Scheme 2) and no 2-hydroxyquinoline as a result
of C–O bond formation was detected in the reaction mixture.
1
[Pd]
Cu
R
H2O
Path a
Path b
N
N
Pd Cl
N
OH
R
Z
Scheme 1. Reactivity of 2-chloroquinoline (1) toward nucleophiles under Pd–Cu
catalysis.
For a comparative study, the coupling reaction of 1 with 2-
methyl but-3-yn-2-ol (2a) was investigated in a number of solvents
including water using Pd/C–CuI–PPh3 as a catalyst system at 80 ꢀC
(Table 1). Initially, the reaction was carried out in DMF for 5 h when
the product 3a was isolated in 67% yield (entry 1, Table 1). However,
the yield increased to 83% with the increase of reaction time to 10 h
(entry 2, Table 1). Further increase in time did not improve the
product yield. The use of other solvents such as THF, MeCN, and
dioxane was also examined (entries 3–5, Table 1). While the cou-
pling reaction proceeded well in all these solvents affording good
yields of product (3a) the best result, however, was achieved by
using water as a solvent (entry 6, Table 1). The use of 2-
10% Pd/C, PPh3, CuI
+
R
Et3N, H2O, 80 °C
N
OH
not detected
Scheme 2. Pd/C-mediated coupling reaction of 2-chloroquinoline in water.
N
N
Cl
3
R
1
2

E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
7145
Table 2
Pd/C-mediated synthesis of 2-alkynylquinolines in watera
Entry
1
Alkynes (2) R¼
Productsb (3)
Yieldc (%)
87
–C(CH3)2OH
–CH2OH
2a
2b
3a
3b
N
N
OH
OH
2
3
89
86
OH
–CH2CH2OH
2c
3c
N
OH
4
5
–(CH2)2CH2OH
2d
3d
82
85
N
OH
–(CH2)3CH2OH
2e
2f
3e
3f
N
HO
6
–CH2CH(OH)CH3
93
N
HO
OH
7
8
2g
2h
3g
3h
96
92
N
–(CH2)3CH3
–(CH2)4CH3
N
9
2i
2j
3i
3j
85
88
N
10
–(CH2)5CH3
N
CN
Cl
11
12
–(CH2)3CN
2k
2l
3k
3l
90
94
N
–(CH2)2CH2Cl
N
13
14
–C6H5
2m
2n
3m
3n
87
84
N
–C6H4CH3-p
N
15
16
2o
3o
91
N
–C6H4F-m
2p
2q
3p
3q
90
89
N
F
17
N
a
All the reactions were carried out by using 1 (1.0 equiv), 2 (1.5 equiv), 10% Pd/C (0.026 equiv), PPh3 (0.20 equiv), CuI (0.05 equiv), and Et3N (3 equiv) at 80 ꢀC for 10 h.
b
c
Identified by 1H NMR, IR, and MS.
Isolated yields.

7146
E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
R
Cl
Cl
N
10% Pd/C, PPh3, CuI
R
+
Et3N, H2O, 80 °C
N
N
6
Cl
Cl
R
R = -(CH2)5CH3
5
4
2j
not detected
Scheme 3.
Heligmosomoides polygyrus and the protozoa Trichomonas vagi-
nalis.2 Compound 3p is of interest for the treatment of disorder
2-chloroquinoline was observed. The use of 2,4-dichloroquinoline
afforded monosubstituted product i.e., 2-alkynyl-4-chloro quino-
line with high regioselectivity. The methodology was also found to
be effective for the alkynylation of 1-chloroisoquinoline and 3-
methyl-2-chloroquinoline. While the process is not free from the
use of phosphine ligands, however, it does not involve the use of
hazardous as well as expensive organic co-solvents and thus min-
imize waste production and environmental pollution. The process,
therefore, is safe in handling and permits to access quinoline de-
rivatives not only for laboratory use but also for large-scale pro-
duction. Since novel quinoline derivatives are in great demands due
to the rise of the resistance level of malarial parasite in the use of
anti-malarial drug chloroquine, we believe that the present meth-
odology would certainly help to generate diversity based quinoline
library for the identification of better anti-malarial agents.
mediated by metabotropic glutamate receptor subtype
5
(mGluR5).19
Mechanistically, the Pd/C-mediated alkynylation of 2-chloro-
quinoline (1) proceeds via generation of an active Pd(0) species in
situ that undergoes oxidative addition with 1 to give the organo-
Pd(II) species Z (Scheme 1). However, generation of active Pd(0)
species involves20 a Pd leaching process, in which Pd leaches into
the solution and becomes an active species by interacting with
phosphine ligands. The active species is therefore a dissolved
Pd(0)–PPh3 complex that actually catalyzes the C–C bond forming
reaction. Thus, the minor portion of the bound palladium (Pd/C)
leached into the solution is the actual catalytic species, indicating
that the catalytic cycle works in solution rather than on the surface.
At the end of the reaction Pd re-precipitates on the surface of the
charcoal.20b Once generated, the organo-Pd(II) species Z then un-
dergoes trans organometallation with copper acetylide (path b,
Scheme 1) generated in situ from CuI and terminal alkyne followed
by reductive elimination of Pd(0) to afford 2-alkynylquinoline 3.
The higher reactivity of copper acetylide perhaps did not allow
water molecules, although present in excess, to interact with Z
thereby preventing the hydrolysis of 2-chloroquinoline 1 (path b,
Scheme 1). It is known that due to the presence of electronegative
nitrogen atom the chloro group at the azomethine carbon is more
susceptible to undergo oxidative addition with Pd(0)9a,21 than
chlorobenzene. This clearly explains the participation of 2-chloro-
quinoline in the alkynylation reaction in water when chloroben-
zene was found to be inactive11b under the conditions. Moreover,
the higher reactivity of chloro group at C-2 over C-4 position on the
quinoline ring in addition to the coordination of quinoline nitrogen
to the palladium13 explains the observed regioselectivity in alky-
nylation of 2,4-dichloroquinoline at C-2 position.
4. Experimental section
4.1. General information
Unless stated otherwise, reactions were monitored by thin layer
chromatography (TLC) on silica gel plates (60 F254), visualizing with
ultraviolet light or iodine spray. Flash chromatography was per-
formed on silica gel (60–120 mesh) using distilled petroleum ether
and ethyl acetate. 1H and 13C NMR spectra were determined in
DMSO-d6 solution using 400 and 50 MHz spectrometers, re-
spectively. Proton chemical shifts (d) are relative to tetramethylsi-
lane (TMS,
d¼0.0) as internal standard and expressed in parts per
million. Spin multiplicities are given as s (singlet), d (doublet), t
(triplet), and m (multiplet) as well as br (broad). Coupling constants
(J) are given in hertz. Infrared spectra were recorded on a FTIR
spectrometer. Melting points were determined by using thermal
analysis [differential scanning calorimetry (DSC)] was generated
with the help of DSC-60A detector. MS spectra were obtained on
a mass spectrometer. Chromatographic purity by HPLC was de-
termined by using area normalization method and the condition
specified in each case: column, mobile phase (range used), flow
rate, detection wavelength, and retention times. All the terminal
alkynes and 2-chloroquinoline used are commercially available.
2,4-Dichloroquinoline was prepared according to the known
procedure.17
Having demonstrated the high reactivity of 2-chloroquinolines
toward Pd/C-mediated alkynylation in pure water we then decided
to examine the reactivity of other chloroquinolines under the same
reaction conditions. Accordingly, commercially available 1-chloro-
isoquinoline (7) was reacted with phenylacetylene (2m) in the
presence of Pd/C–CuI–PPh3 as a catalyst system at 80 ꢀC for 10 h in
water. The desired product 1-phenylethynyl isoquinoline22 (8) was
isolated in 85% yield. Similarly, reaction of 3-methyl-2-chloro-
quinoline23 (9) with 1-hexyne (2h) afforded 2-hex-1-ynyl-3-
methyl quinoline9a (10) in 60% yield.
4.2. General procedure for the synthesis of 2-
alkynylquinolines (3)
3. Conclusions
A mixture of 2-chloroquinoline (1) (1.42 mmol), 10% Pd/C
(0.037 mmol), PPh3 (0.28 mmol), CuI (0.07 mmol), and triethyl-
amine (4.26 mmol) in water (10 mL) was stirred at 25–30 ꢀC for
30 min under nitrogen. The acetylinic compound (2) (2.14 mmol)
was added, and the mixture was initially stirred at room temper-
ature for 1 h and then at 80 ꢀC for 10 h. After completion of the
reaction, the mixture was cooled to room temperature, diluted with
EtOAc (50 mL), and filtered through Celite. The organic layers were
collected, washed with water (3ꢁ30 mL), dried over anhydrous
In summary, Pd/C–CuI–PPh3 proved to be an efficient catalyst
system for the cross-coupling of 2-chloroquinoline with a variety of
terminal alkynes in water providing a general and practical method
for the preparation of functionalized 2-alkynylquinolines in good to
high yields. The air and moisture stable catalyst Pd/C can be re-
covered and reused. The reaction proceeds well with both hydro-
phobic and hydrophilic terminal alkynes and no significant side
reactions such as dimerization of terminal alkynes or hydrolysis of

E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
7147
Na2SO4, and concentrated. The crude residue was purified by col-
umn chromatography on silica gel using light petroleum (60–
80 ꢀC)/ethyl acetate to afford the desired product.
(m, 2H), 3.88–3.73 (m, 2H), 2.86–2.63 (m, 2H), 1.96–1.26 (m, 2H); IR
(cmꢂ1, neat) 3331 (br), 3059, 2947, 2225, 1595, 1425; m/z (ES mass)
212 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.2, 143.3, 135.9,
131.7, 131.5, 129.7, 129.1, 128.3, 128.1, 91.6, 80.7, 60.4, 30.6, 15.6;
HPLC 97.97%, column: Inertsil ODS3V (150ꢁ4.6 mm), mobile phase
A: 0.01 M KH2PO4, mobile phase B: CH3CN, gradient (T/%B): 0/30,
4/30, 15/80, 22/80, 24/30, 25/30; flow rate: 1.5 mL/min; UV 250 nm,
retention time 7.0 min; HRMS (ESI): calcd for C14H13NO (MþH)þ
212.1075, found 212.1083.
4.2.1. 2-Methyl-4-quinolin-2-yl-but-3-yn-2-ol (3a)
N
OH
Low melting solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-hexane)
0.18; 1H NMR (CDCl3, 400 MHz)
4.2.5. 6-Quinolin-2-yl-hex-5-yn-1-ol (3e)
d
8.11 (d, J¼8.5 Hz, 2H), 7.79–7.69
(m, 2H), 7.55–7.26 (m, 2H), 1.68 (s, 6H); IR (cmꢂ1, KBr) 3240, 3068,
2964, 2223, 1593; m/z (ES mass) 212 (Mþ1, 100%); 13C NMR (CDCl3,
50 MHz) 147.3, 143.3, 135.9, 131.7, 129.7, 129.1, 128.3, 128.1, 127.1,
90.6, 80.7, 60.4, 30.6, 15.6; HPLC: 98.0%, column: Symmetry Shield
RP18 (150ꢁ4.6 mm), mobile phase A: 0.01 M KH2PO4, mobile phase
B: CH3CN, gradient (T/%B): 0/30, 4/30, 14/80, 20/80, 21/30, 22/30;
flow rate: 1.5 mL/min; UV 210 nm, retention time 7.1 min; HRMS
(ESI): calcd for C14H13NO (MþH)þ 212.1075, found 212.1069.
OH
N
Low melting brown solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-
hexane) 0.21; 1H NMR (CDCl3, 400 MHz)
d
8.09 (dd, J¼8.3 and
2.9 Hz, 2H), 7.78–7.70 (m, 1H), 7.69–7.66 (m, 1H), 7.56–7.44 (m, 2H),
3.68 (t, J¼6.7 Hz, 2H), 2.57–2.55 (m, 2H), 2.30 (t, J¼6.8 Hz, 2H),1.79–
1.78 (m, 2H); IR (cmꢂ1, KBr) 3304, 3053, 2947, 2223, 1593; m/z (ES
mass) 226 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.4, 143.5,
135.9, 131.8, 131.7, 129.7, 128.2, 126.6, 126.5, 91.8, 80.9, 61.4, 31.5
(2C), 24.3; HPLC: 92.36%, column: Inertsil ODS3V (150ꢁ4.6 mm),
mobile phase A: 0.01 M KH2PO4, mobile phase B: CH3CN, gradient
(T/%B): 0/20, 2/20, 14/80, 22/80, 24/20, 25/20; flow rate: 1.5 mL/
min; UV 210 nm, retention time 8.9 min; HRMS (ESI): calcd for
4.2.2. 3-Quinolin-2-yl-prop-2-yn-1-ol (3b)
OH
N
Low melting brown solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-
hexane) 0.2; 1H NMR (CDCl3, 400 MHz)
d 8.12–8.07 (m, 2H), 7.80–
C
15H15NO (MþH)þ 226.1232, found 226.1213.
7.70 (m, 2H), 7.56–7.26 (m, 2H), 4.61 (s, 2H); IR (cmꢂ1, KBr) 3224,
3061, 2918, 2218; m/z (ES mass) 184 (Mþ1, 100%); 13C NMR (CDCl3,
50 MHz) 147.3, 142.7, 136.3, 130.0, 128.3, 127.3, 127.0 (2C), 126.9,
89.8, 84.2, 50.6; HPLC: 98.37%, column: Inertsil ODS3V
(150ꢁ4.6 mm), mobile phase A: 0.01 M H2PO4, mobile phase B:
CH3CN, gradient (T/%B): 0/20, 2/20, 14/80, 22/80, 24/20, 25/20; flow
rate: 1.5 mL/min; UV 210 nm, retention time 6.9 min; HRMS (ESI):
calcd for C12H9NO (MþH)þ 184.0762, found 184.0754.
4.2.6. 5-Quinolin-2-yl-pent-4-yn-2-ol (3f)
HO
N
Low melting solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-hexane)
4.2.3. 4-Quinolin-2-yl-but-3-yn-1-ol (3c)
0.18; 1H NMR (CDCl3, 400 MHz)
d
8.07 (dd, J¼7.8 Hz, 2H), 7.77–7.68
(m, 2H), 7.51–7.44 (m, 2H), 4.20–4.15 (m, 1H), 2.70–2.67 (m, 2H),
1.38–1.36 (d, J¼5.8 Hz, 3H); IR (cmꢂ1, neat) 3344 (br), 3061, 2981,
2229, 1595; m/z (ES mass) 212 (Mþ1, 100%); 13C NMR (CDCl3,
50 MHz) 147.2, 143.2, 136.1, 129.8 (2C), 128.2, 127.2 (2C), 126.6 (2C),
123.8, 89.1, 82.3, 29.8; HPLC: 99.02%, column: Symmetry Shield
RP18 (150ꢁ4.6 mm), mobile phase A: 0.01 M KH2PO4, mobile
phase B: CH3CN, gradient (T/%B): 0/30, 4/30, 14/80, 20/80, 21/30,
22/30; flow rate: 1.5 mL/min; UV 210 nm, retention time
6.6 min; HRMS (ESI): calcd for C14H13NO (MþH)þ 212.1075, found
212.1068.
OH
N
Browngum;Rf (20%ethylacetate/n-hexane)0.16; 1HNMR(CDCl3,
400 MHz)
d
8.35 (d, J¼8.7 Hz,1H), 7.97 (t, J¼8.3 Hz,1H), 7.80–7.78 (m,
1H), 7.64–7.59 (m, 2H), 7.55 (d, J¼8.3 Hz, 1H), 3.65 (t, J¼6.5 Hz, 2H),
2.65 (t, J¼6.5 Hz, 2H); IR (cmꢂ1, neat) 3344, 3000, 2935, 2227, 1595;
m/z (ES mass) 198 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 150.4,
147.7, 136.9, 136.6, 133.6, 132.1, 132.0, 131.6, 128.6, 88.0 (2C), 60.5,
29.5; HPLC: 93.26%, column: Inertsil ODS3V (150ꢁ4.6 mm), mobile
phase A: 0.01 M KH2PO4, mobile phase B: CH3CN, gradient (T/%B):
0/25, 3/25, 14/80, 22/80, 24/25, 25/25; flow rate: 1.5 mL/min; UV
250 nm, retention time 7.2 min; Elemental analysis found C, 79.21;
H, 5.60; N, 7.01; C13H11NO requires C, 79.16; H, 5.62; N, 7.10.
4.2.7. 1-Quinolin-2-ylethynyl-cyclohexanol (3g)
HO
N
4.2.4. 5-Quinolin-2-yl-pent-4-yn-1-ol (3d)
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.25; 1H NMR
(CDCl3, 400 MHz)
d
8.10 (d, J¼8.3 Hz, 2H), 7.79–7.77 (m, 1H), 7.73–
OH
7.69 (m, 1H), 7.55–7.48 (m, 2H), 2.12–2.07 (m, 2H), 1.80–1.63 (m,
4H), 1.60–1.56 (m, 4H); IR (cmꢂ1, neat) 3332 (br), 3059, 2933,
2225, 1593; m/z (ES mass) 252 (Mþ1, 100%); 13C NMR (CDCl3,
50 MHz) 147.3, 143.0, 135.8, 135.8, 129.7 (2C), 129.6, 128.5 (2C),
127.1 (2C), 94.9, 83.5, 29.3, 24.9, 22.9 (2C); HPLC: 99.79%, column:
Acquity UPLCBEHC18 (2.1ꢁ100 mm), mobile phase A: 0.1% TEA,
N
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.15; 1H NMR
(CDCl3, 400 MHz) d 8.09–8.06 (m, 2H), 7.78–7.60 (m, 2H), 7.54–7.44

7148
E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
mobile phase B: CH3CN, gradient (T/%B): 0/50, 1/50, 5/80, 9/80,
10/50, 12/50; flow rate: 1.5 mL/min; UV 249 nm, retention time
2.5 min; HRMS (ESI): calcd for C17H17NO (MþH)þ 252.1388, found
252.1376.
4.2.11. 6-Quinolin-2-yl-hex-5-ynenitrile (3k)
CN
N
4.2.8. 2-Hex-1-ynyl-quinoline (3h)
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.35; 1H NMR
(CDCl3, 400 MHz)
d 8.11–8.06 (m, 2H), 7.79–7.71 (m, 2H), 7.55–7.51
(m, 2H), 2.70 (t, J¼6.8 Hz, 2H), 2.60 (t, J¼6.8 Hz, 2H), 2.07–2.00 (m,
2H); IR (cmꢂ1, neat) 3059, 2941, 2227,1593,1493; m/z (ES mass) 221
(Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.6, 143.0, 135.9, 129.7,
128.7, 127.2, 127.0, 126.7, 123.8, 118.8, 88.1, 82.3, 23.9, 18.2, 16.0;
HPLC: 99.72%, column: Symmetry Shield RP18 (150ꢁ4.6 mm),
mobile phase A: 0.01 M KH2PO4, mobile phase B: CH3CN, gradient
(T/%B): 0/30, 2/30,12/80,18/80,19/30, 20/30; flow rate: 1.5 mL/min;
UV 248 nm, retention time 7.5 min; HRMS (ESI): calcd for C15H12N2
(MþH)þ 221.1079, found 221.1073.
N
Brown oil; Rf (20% ethyl acetate/n-hexane) 0.24; 1H NMR (CDCl3,
400 MHz)
d
8.06 (dd, J¼8.3 and 3.4 Hz, 2H), 7.76 (d, J¼7.8 Hz, 1H),
7.69–7.66 (m, 1H), 7.52–7.50 (m, 1H), 7.45 (d, J¼8.3 Hz, 1H), 2.50 (t,
J¼7.3 Hz, 2H), 1.68–1.64 (m, 2H), 1.56–1.47 (m, 2H), 0.96 (t, J¼7.3 Hz,
3H); IR (cmꢂ1, neat) 3059, 2956, 2225, 1596; m/z (ES mass) 210
(Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.7, 143.8, 135.6, 129.5,
128.8, 127.1, 126.6, 126.4, 126.3, 91.4, 80.3, 30.1, 21.8, 18.9, 13.3; HPLC
99.75%, column: Inertsil ODS3V, mobile phase A: 0.01 M KH2PO4,
mobile phase B: CH3CN, gradient (T/%B): 0/50, 2/50, 20/80, 27/80,
29/50, 30/50; flow rate: 1.5 mL/min; UV 210 nm, retention time
11.6 min; HRMS (ESI): calcd for C15H15N (MþH)þ 210.1283, found
210.1259.
4.2.12. 2-(5-Chloro-pent-1-unyl)-quinoline (3l)
Cl
N
4.2.9. 2-Hept-1-ynyl-quinoline (3i)
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.34; 1H NMR
(CDCl3, 400 MHz)
d
8.08 (t, J¼8.5 Hz, 2H), 7.79–7.69 (m, 2H), 7.51–
7.26 (m, 2H), 3.74 (t, J¼6.4 Hz, 2H), 2.71 (t, J¼6.8 Hz, 2H), 2.15–1.70
(m, 2H); IR (cmꢂ1, neat) 3059, 2926, 2227, 1593; m/z (ES mass) 230
(Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.8, 143.4, 135.8, 129.8,
129.2, 128.9, 127.2 (2C), 126.7, 89.5, 81.7, 43.5, 30.8, 16.7; HPLC:
98.90%, column: Inertsil ODS3V (150ꢁ4.6 mm), mobile phase A:
0.01 M KH2PO4, mobile phase B: CH3CN, gradient (T/%B): 0/55, 2/55,
7/80, 18/80, 19/55, 20/55; flow rate: 1.5 mL/min; UV 210 nm, re-
tention time 5.9 min; HRMS (ESI): calcd for C14H12ClN (MþH)þ
230.0737, found 230.0731.
N
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.2; 1H NMR
(CDCl3, 400 MHz)
d
8.08 (dd, J1¼8.3 Hz, J2¼3.9 Hz, 2H), 7.77–7.66
(m, 2H), 7.52–7.43 (m, 2H), 2.49 (t, J¼7.3 Hz, 2H), 1.71–1.63 (m,
2H), 1.51–1.41 (m, 4H), 0.93 (t, J¼7.3 Hz, 3H); IR (cmꢂ1, neat) 3061,
2958, 2224, 1595; m/z (ES mass) 224 (Mþ1, 100%); 13C NMR
(CDCl3, 50 MHz) 147.4, 143.5, 135.3, 129.2, 128.7, 128.4, 126.8,
126.3, 126.1, 91.5, 80.6, 30.6, 29.1, 28.8, 21.6, 13.4; HPLC: 99.45%,
column: Inertsil ODS3V (150ꢁ4.6 mm), mobile phase A: 0.01%
TFA, mobile phase B: CH3CN, gradient (T/%B): 0/60, 2/60, 12/80,
18/80, 19/60, 20/60; flow rate: 1.5 mL/min; UV 210 nm, retention
time 8.4 min; HRMS (ESI): calcd for C16H17N (MþH)þ 224.1439,
found 224.1433.
4.2.13. 2-Phenylethynyl-quinoline (3m)
N
White solid, mp 64–65 ꢀC; Rf (20% ethyl acetate/n-hexane) 0.3;
1H NMR (CDCl3, 400 MHz)
d
8.13 (dd, J¼8.3 and 2.9 Hz, 2H), 7.80 (d,
4.2.10. 2-Oct-1-ynyl-quinoline (3j)
J¼7.8 Hz, 1H), 7.75–7.71 (m, 2H), 7.68–7.61 (m, 2H), 7.58 (d,
J¼7.8 Hz, 1H), 7.56–7.52 (m, 1H), 7.39–7.37 (m, 2H); IR (cmꢂ1, KBr)
3059, 2922, 2208, 1591, 1498; m/z (ES mass) 230 (Mþ1, 100%); 13C
NMR (CDCl3, 50 MHz) 147.61, 142.9, 135.7, 131.7, 129.5, 129.0, 128.7,
128.6, 127.9 (2C), 127.0 (2C), 123.8 (2C), 121.6, 89.6, 89.0; HPLC:
99.48%, column: Inertsil ODS3V (150ꢁ4.6 mm), mobile phase A:
0.01 M KH2PO4, mobile phase B: CH3CN, gradient (T/%B): 0/60, 2/60,
8/80, 18/80, 19/60, 20/60; flow rate: 1.5 mL/min; UV 210 nm, re-
tention time 6.76 min; HRMS (ESI): calcd for C17H11N (MþH)þ
230.0970, found 230.0960.
N
Low melting solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-hexane)
0.25; 1H NMR (CDCl3, 400 MHz)
d 8.08–8.05 (m, 2H), 7.77–7.70 (m,
2H), 7.69–7.50 (m, 2H), 2.61–2.47 (m, 2H), 1.74–1.63 (m, 4H), 1.51–
1.30 (m, 4H), 0.93–0.89 (m, 3H); IR (cmꢂ1, neat) 3059, 2927, 2225,
1595; m/z (ES mass) 238 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz)
147.4, 143.5, 135.4, 129.2, 128.7, 128.4, 126.8, 126.5, 126.1, 91.6, 80.6,
30.8, 29.2, 28.1, 27.8, 23.6, 13.5; HPLC: 99.51%, column: Acquity
UPLCBEHC18 (2.1ꢁ100 mm), mobile phase A: 0.01% TFA, mobile
phase B: CH3CN, gradient (T/%B): 0/50, 2/50, 6/80, 12/80, 13/50,
14/50; flow rate: 1.5 mL/min; UV 249 nm, retention time 6.5 min;
Elemental analysis found C, 86.17; H, 8.01; N, 5.95; C17H19N requires
C, 86.03; H, 8.07; N, 5.90.
4.2.14. 2-p-Tolylethyl-quinoline (3n)
N
White solid, mp 98–100 ꢀC; Rf (20% ethyl acetate/n-hexane) 0.3;
1H NMR (CDCl3, 400 MHz)
(d, J¼8.3 Hz, 1H), 7.78–7.70 (m, 2H), 7.60–7.25 (m, 3H), 7.19 (d,
d
8.12 (dd, J1¼8.5 Hz, J2¼3.7 Hz, 2H), 7.79

E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
7149
J¼8.3 Hz, 2H), 2.38 (s, 3H); IR (cmꢂ1, KBr) 3043, 2914, 2220, 1591;
4.3. Synthesis of 4-chloro-2-oct-1-ynyl-quinoline (5)
m/z (ES mass) 244 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 148.0,
143.6, 139.9, 135.9 (2C), 131.9 (2C), 129.8 (2C), 129.0 (2C), 127.3 (2C),
126.8, 124.1, 90.1, 88.7, 21.4; HPLC: 97.9%, column: Inertsil ODS3V
(150ꢁ4.6 mm), mobile phase A: 0.01 M KH2PO4, mobile phase B:
CH3CN, gradient (T/%B): 0/60, 2/60, 8/80, 18/80, 19/60, 20/60; flow
rate: 1.5 mL/min; UV 250 nm, retention time 8.13 min; HRMS (ESI):
calcd for C18H13N (MþH)þ 244.1126, found 244.1135.
Cl
N
4.2.15. 2-(4-Pentyl-phenylethynyl)-quinoline (3o)
A mixture of 2,4-dichloroquinoline (4) (2.84 mmol), 10% Pd/C
(0.074 mmol), PPh3 (0.56 mmol), CuI (0.14 mmol), and triethyl-
amine (8.52 mmol) in water (20 mL) was stirred at 25–30 ꢀC for
30 min under nitrogen. To this mixture was added 1-octyne (2j)
(4.28 mmol) and the mixture was initially stirred at room tem-
perature for 1 h and then at 80 ꢀC for 8 h. After completion of the
reaction, the mixture was cooled to room temperature, diluted with
EtOAc (110 mL), and filtered through Celite. The organic layers were
collected, washed with water (3ꢁ50 mL), dried over anhydrous
Na2SO4, and concentrated. The crude residue was purified by col-
umn chromatography on silica gel, using light petroleum (60–
80 ꢀC)/ethyl acetate to afford 4-chloro-2-oct-1-ynyl-quinoline (82%
yield). Low melting brown solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-
N
Brown oil; Rf (20% ethyl acetate/n-hexane) 0.3; 1H NMR (CDCl3,
400 MHz)
d 8.09–8.06 (m, 2H), 7.77–7.71 (m, 2H), 7.52–7.47 (m, 5H),
6.42–6.39 (m, 1H), 2.31–2.27 (m, 4H), 1.72–1.60 (m, 7H); IR (cmꢂ1
,
neat) 3050, 2929, 2200,1593,1498; m/z (ES mass) 300 (Mþ1,100%);
13C NMR (CDCl3, 50 MHz) 147.6, 143.5, 137.3, 135.4 (2C), 129.3 (2C),
128.6 (2C), 126.9, 126.3, 126.2, 123.2 (2C), 119.7, 91.7, 86.7, 28.2, 25.4,
21.7 (2C), 20.9; HPLC: 97.49%, column: Acquity UPLCBEHC18
(2.1ꢁ100 mm), mobile phase A: 0.1% TEA, mobile phase B: CH3CN,
gradient (T/%B): 0/50, 1/50, 5/80, 9/80, 10/50, 12/50; flow rate:
1.5 mL/min; UV 213 nm, retention time 5.19 min; HRMS (ESI): calcd
for C18H13N (MþH)þ 244.1126, found 244.1135.
hexane) 0.18; 1H NMR (CDCl3, 400 MHz)
d 8.18–8.07 (m, 2H), 7.77–
7.60 (m, 2H), 7.55 (s, 1H), 2.48 (t, J¼7.0 Hz, 2H), 1.70–1.63 (m, 2H),
1.58–1.44 (m, 2H), 1.36–1.28 (m, 4H), 0.92–0.89 (m, 3H); 13C NMR
(CDCl3, 50 MHz) 148.4, 143.4, 141.9, 130.3, 129.2, 127.3, 124.9, 123.7,
123.4, 92.8, 80.0, 31.0, 28.4, 27.9, 22.2, 19.2, 13.7; IR (cmꢂ1, neat)
3057, 2927, 2216, 1593; m/z (ES mass) 272 (Mþ1, 100%); HPLC:
99.58%, column: ACE 5 C8 (250ꢁ4.6 mm), mobile phase A: 0.01 M
H2PO4, mobile phase B: CH3CN, gradient (T/%B): 0/40, 2/40, 4/45,
25/45, 28/40, 32/40; flow rate: 1.0 mL/min; UV 252 nm, retention
time 9.74 min; HRMS (ESI): calcd for C17H18ClN (MþH)þ 272.1205,
found 272.1206.
4.2.16. 2-(3-Fluoro-phenylethynyl)-quinoline (3p)
N
F
White solid, mp 75–77 ꢀC; Rf (20% ethyl acetate/n-hexane) 0.27;
4.4. 1-Phenylethynyl isoquinoline22 (8)
1H NMR (CDCl3, 400 MHz)
d
8.14 (t, J¼8.5 Hz, 2H), 7.81 (d, J¼7.8 Hz,
1H), 7.76–7.74 (m, 2H), 7.72–7.54 (m, 2H), 7.10–7.08 (m, 3H); IR
(cmꢂ1, neat) 3057, 2924, 2208, 1606, 1500; m/z (ES mass) 248 (Mþ1,
100%); 13C NMR (CDCl3, 50 MHz) 164.6, 148.0, 142.9, 136.1, 130.0,
129.8, 128.0 (2C), 127.9, 127.4, 127.1, 124.1, 123.9, 123.7, 116.6, 89.9,
88.2; HPLC: 98.42%, column: Acquity UPLCBEHC18 (2.1ꢁ100 mm),
mobile phase A: 0.1% TEA, mobile phase B: CH3CN, gradient (T/%B):
0/40, 1/40, 5/80, 8/80, 9/40, 10/40; flow rate: 1.5 mL/min; UV
210 nm, retention time 5.1 min; HRMS (ESI): calcd for C17H10FN
(MþH)þ 248.0876, found 248.0887.
N
Light yellow oil; Rf (20% ethyl acetate/n-hexane) 0.28; 1H NMR
(CDCl3, 400 MHz)
d
8.47 (d, J¼5.6 Hz, 1H), 8.42 (d, J¼8.3 Hz, 1H),
4.2.17. 2-(4-Phenyl-but-1-ynyl)-quinoline (3q)
7.76 (d, J¼7.5 Hz, 1H), 7.60 (m, 4H), 7.56 (d, J¼5.9 Hz, 1H), 7.33 (m,
3H); 13C NMR (CDCl3, 50 MHz) 144.2, 142.8, 135.7, 132.1, 130.5,
129.2, 129.1, 128.4, 127.9, 126.8, 126.8, 122.1, 120.5, 93.9, 86.7; IR
(cmꢂ1, KBr) 3045, 2925, 2212, 1590; m/z (ES mass) 230 (Mþ1, 100%).
N
4.5. 2-Hex-1-ynyl-3-methyl quinoline9a (10)
Low melting brown solid, mp<25 ꢀC; Rf (20% ethyl acetate/n-
hexane) 0.28; 1H NMR (CDCl3, 400 MHz)
d 8.08–8.05 (m, 2H), 7.75
(d, J¼8.3 Hz, 1H), 7.71–7.67 (m, 1H), 7.52–7.48 (m, 1H), 7.40 (d,
J¼8.3 Hz, 1H), 7.33–7.28 (m, 5H), 3.00 (t, J¼7.8 Hz, 2H), 2.78 (t,
J¼7.8 Hz, 2H); IR (cmꢂ1, neat) 3061, 2930, 2226, 1594; m/z (ES mass)
258 (Mþ1, 100%); 13C NMR (CDCl3, 50 MHz) 147.2, 143.1, 139.6,
135.3,129.2,128.7,128.3,127.7,127.3,127.1,126.7,126.4,126.2,126.0,
125.7, 90.43, 81.18, 33.99, 20.9; HPLC: 99.01%, column: Inertsil
ODS3V (150ꢁ4.6 mm), mobile phase A: 0.01% TFA, mobile phase B:
CH3CN, gradient (T/%B): 0/60, 2/60, 12/80, 18/80, 19/60, 20/60; flow
rate: 1.5 mL/min; UV 210 nm, retention time 7.2 min; HRMS (ESI):
calcd for C19H15N (MþH)þ 258.1283, found 258.1275.
N
Brown gum; Rf (20% ethyl acetate/n-hexane) 0.22; 1H NMR
(CDCl3, 400 MHz)
d
8.01 (d, J¼8.3 Hz, 1H), 7.83 (d, J¼0.7 Hz, 1H),
7.64–7.54 (m, 2H), 7.44 (dd, J¼7.2 and 0.5 Hz, 1H), 2.51 (t, J¼7.3 Hz,
2H), 2.50 (s, 3H), 1.68–1.64 (m, 2H), 1.56–1.46 (m, 2H), 0.96 (t,

7150
E.A. Reddy et al. / Tetrahedron 64 (2008) 7143–7150
J¼7.3 Hz, 3H); IR (cmꢂ1, neat) 3060, 2955, 2226; m/z (ES mass) 224
(Mþ1, 100%).
kanti, S.; Kumara Swamy, N.; Yeleswarapu, K. R.; Alexander, C. W.; Khanna, I. K.;
Iqbal, J.; Pillarisetti, S.; Pal, M.; Barange, D. Novel Pyrimidine Compounds,
Process for their Preparation and Compositions Containing them. World Patent
Application WO 2006034473 A2, March 30, 2006.
Acknowledgements
11. (a) Raju, S.; Kumar, P. R.; Mukkanti, K.; Annamalai, P.; Pal, M. Bioorg. Med. Chem.
Lett. 2006, 16, 6185; (b) Batchu, V. R.; Subramanian, V.; Parasuraman, K.; Swamy,
N. K.; Kumar, S.; Pal, M. Tetrahedron 2005, 61, 9869; See also: (c) Pal, M.; Sub-
ramanian, V.; Parasuraman, K.; Yeleswarapu, K. R. Tetrahedron 2003, 59, 9563.
12. (a) Venkataraman, S.; Barange, D. K.; Pal, M. Tetrahedron Lett. 2006, 47, 7317; (b)
Pal, M.; Khanna, I.; Venkataraman, S.; Srinivas, P.; Sivram, P. Heterocyclic and
Bicyclic Compounds, Compositions and Methods. World Patent Application WO
2006058201, June 1, 2006. (c) Bera, R.; Dhananjaya, G.; Singh, S. N.; Ramu, B.;
Kiran, S. U.; Kumar, P. R.; Mukkanti, K.; Pal, M. Tetrahedron 2008, 64, 582.
13. Based on experimental observations it has been suggested that coordination of
quinoline nitrogen to the palladium controls the coupling reaction at the C-2
position of the quinoline ring, see: (a) Shiota, T.; Yamamori, T. J. Org. Chem. 1999,
64, 453; (b) Legros, J.-Y.; Primault, G.; Fiaud, J.-C. Tetrahedron 2001, 57, 2507.
14. (a) Lee, B. S.; Lee, B. C.; Jun, J.-G.; Chi, D. Y. Heterocycles 1998, 48, 2637; (b) Nasr,
M.; Drach, J. C.; Smith, S. H.; Shipman, C. H., Jr.; Burckhalter, J. H. J. Med. Chem.
1988, 31, 1347; (c) Kaneko, C.; Naito, T.; Momose, Y.; Fujii, H.; Nakayama, N.;
Koizumi, I. Chem. Pharm. Bull. 1982, 30, 519; (d) For nucleophilic substitution
reaction under microwave irradiation, see: Cheng, Y.-J. Tetrahedron 2002, 58,
1125.
The authors thank Dr. V. Dahanukar and Mr. A. Mukherjee for
their encouragement and the analytical group for spectral data. Mr.
E.A.R. thanks CPS-DRL, Hyderabad, India for allowing him to pursue
this work as a part of his Ph.D. program.
References and notes
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erocyclic Compounds; Quinolines; Jones, G., Ed.; John Wiley and Sons: Chichester,
UK, 1982; Vol. 32, Part 2, pp 31–32; (c) Daines, R. A.; Kingsbury, W. D.; Pendrak,
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