Selectivity in metal ions mediated C-N bond formation reactions of 8-aminoquinoline derivatives

Article abstract of DOI:10.1002/poc.1899

Cyclisation reactions via C-N bond formation of 2-bromo-N-(quinolin-8-yl) propanamide (I) and 2-bromo-N-(quinolin-8-yl)acetamide (II) are facilitated by metal salts such as copper (+2), nickel (+2) perchlorate or nitrate and palladium (+2) acetate. Nickel (+2) perchlorate mediated reaction of I and II resulted in C-N bond formation to give corresponding perchlorate salts of three fused six-membered heterocyclic rings. The copper (+2) mediated reactions are found to be solvent dependent for I, but independent for II. Copper mediated reaction of II gave cyclised product analogous to the one obtained from reaction of II with nickel (+2) perchlorate in methanol or ethanol. But the reaction of I with copper (+2) perchlorate in methanol gave C-N bonded methoxylated cyclised product. This reaction took place in two steps, cyclisation followed by methoxylation. The source of methoxy group is confirmed to be from methanol by deuterium labelling experiments. Whereas similar copper mediated reaction of I in ethanol led to nucleophilic substitution of bromide ion by ethoxide. The structures of the salts of fused heterocyclic compounds were determined and their fluorescence emissions were studied. The large difference in fluorescence emission of compound V formed from copper mediated reaction in ethanol from the compound VI formed from nickel mediated reaction in methanol or ethanol, this feature can be used to distinguish nickel (+2) and copper (+2) ions. The reaction of II with palladium (+2) acetate resulted in the formation of C-N bond to yield the corresponding heterocycle as bromide salt; without anion exchange.

Full text of DOI:10.1002/poc.1899

Research Article
Received: 1 March 2011,
Revised: 3 June 2011,
Accepted: 5 June 2011
Published online in Wiley Online Library: 20 July 2011
(wileyonlinelibrary.com) DOI: 10.1002/poc.1899
Selectivity in metal ions mediated C–N bond
formation reactions of 8-aminoquinoline
derivatives
Dipjyoti Kalitaa and Jubaraj B. Baruaha*
Cyclisation reactions via C–N bond formation of 2-bromo-N-(quinolin-8-yl)propanamide (I) and 2-bromo-N-(quinolin-
8-yl)acetamide (II) are facilitated by metal salts such as copper (+2), nickel (+2) perchlorate or nitrate and palladium
(+2) acetate. Nickel (+2) perchlorate mediated reaction of I and II resulted in C–N bond formation to give
corresponding perchlorate salts of three fused six-membered heterocyclic rings. The copper (+2) mediated reactions
are found to be solvent dependent for I, but independent for II. Copper mediated reaction of II gave cyclised product
analogous to the one obtained from reaction of II with nickel (+2) perchlorate in methanol or ethanol. But the reac-
tion of I with copper (+2) perchlorate in methanol gave C–N bonded methoxylated cyclised product. This reaction
took place in two steps, cyclisation followed by methoxylation. The source of methoxy group is confirmed to be from
methanol by deuterium labelling experiments. Whereas similar copper mediated reaction of I in ethanol led to
nucleophilic substitution of bromide ion by ethoxide. The structures of the salts of fused heterocyclic compounds
were determined and their fluorescence emissions were studied. The large difference in fluorescence emission of
compound V formed from copper mediated reaction in ethanol from the compound VI formed from nickel mediated
reaction in methanol or ethanol, this feature can be used to distinguish nickel (+2) and copper (+2) ions. The reaction
of II with palladium (+2) acetate resulted in the formation of C–N bond to yield the corresponding heterocycle as
bromide salt; without anion exchange. Copyright # 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: 8-aminoquinoline; anion binding; C–N bond formation; metal mediated synthesis; role of solvent; selective
transformations
and in aprotic solvents.[29,30] Thus, the competitive reactions of
cyclisation versus nucleophilic substitution reactions in the pres-
INTRODUCTION
ence or absence of metal ions are of interest. Here, we studied
the copper (+2) and nickel (+2) ion mediated reactions of 2-
bromo-N-(quinolin-8-yl) propanamide (I) and 2-bromo-N-(quino-
lin-8-yl) acetamide (II) and 2-bromo-N-(quinolin-5-yl) acetamide
(III) (Fig. 1) in alcohols and show that the fluorescence emission
properties of the products can be useful in differentiating
solvents.
Several naturally occurring drug molecules contain quinoline
rings as their constituents.[1–10] Aminoquinoline derivatives are
useful in cyclisation reactions for ring expansion[11–19] and for
the synthesis of steroids.[20,21] Multiple possibilities exist to ob-
tain cyclised products from intramolecular cyclisation reactions
of 8-aminoquinoline derivatives. For example, when an amino
group of 8-aminoquinoline is functionalised to an amide group
linked to a leaving group, such compounds may lead to the for-
mation of new rings in different ways as shown in Scheme 1. The
formation of such products can be controlled by using metal cat-
alysts.[22–25] For example, when N-8-quinoline benzene sulpho-
RESULTS AND DISCUSSION
In the presence of different metal salts of copper(+2) or
nickel (+2) in methanol, 2-bromo-N-(quinolin-8-yl) propana-
mide(I) underwent cyclisation reactions through C–N bond for-
mation to give two different products depending on the metal
ion used (Scheme 2). Such reactions were also found to be sol-
vent dependent. When copper (+2) salts were used in methanol
exclusively methoxylated as well as cyclised product IV was
namides were cyclised in the presence of
a palladium
catalyst,[26] this led to heterocyclic compounds through C–C
bond formation. Novel heterocyclic compounds through intra-
molecular C–C bond formation by palladium catalysed reactions
were observed from imine derivatives of 8-aminoquinoline.[22]
Recently, the coordination effects of amide functionalised
8-aminoquinoline derivatives were used for intramolecular
cyclisation within a compound at a remote end.[27] We have
also shown that intramolecular cyclisation via aldol condensa-
tion leads to interesting heterocyclic products through multiple
paths involving both C–N and C–C bond formation reactions.[28]
Furthermore, the halo derivatives shown in Scheme 1 can also
undergo conventional nucleophilic substitution by nucleophiles
such as water, alcohol, amine etc. in the presence of a base
* Correspondence to: Jubaraj B. Baruah, Department of Chemistry, Indian
Institute of Technology Guwahati, Guwahati, 781 039 Assam, India.
E-mail: juba@iitg.ernet.in
a D. Kalita, J. B. Baruah
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati,
781 039 Assam, India
J. Phys. Org. Chem. 2012, 25 169–175
Copyright # 2011 John Wiley & Sons, Ltd.

D. KALITA AND J. B. BARUAH
O
of the peak positions in 1H-NMR of these compounds can be
clearly discerned. For example, the compound IV has a signal
at 3.5 ppm because of the –OMe group and there is a signal of
a methyl group at 1.9 ppm as a singlet. The compound VI is de-
void of signal from –OMe because of its absence, but it shows a
multiplet signal at 5.8 ppm because of the CH next to the methyl
group. The methyl group of VI has a signal at 1.8 ppm. The com-
pound V has characteristic quartet and triplet from the
OCH2CH3 group (3.4 and 1.0 ppm) and it has a doublet at 1.8
ppm and a quartet at 5.8 ppm from the CH3 and CH groups.
Because nickel (+2) has similar electronic features with palladium
(+2), we carried out the reaction of II with a stoichiometric
amount of palladium (+2) acetate in methanol. It gave the C–N
bond product similar to a nickel-mediated reaction but in the
form of bromide salt. That is, the reaction led to no anion ex-
change. The reaction with nickel (+2) acetate in methanol was
not effective at room temperature. Thus, the metal has a role
in these reactions and anion exchange processes are dependent
on the metal ion in consideration.
O
X
N
O
HN
HN
NH
X
N
N
+ HX
C-N bond formation X = Leaving group C-C bond formation
A
B
Scheme 1. Two different ways to cyclise in 8-aminoquinoline derivatives
N
N
N
HN
O
HN
O
HN
O
Br
Br
Br
III
II
I
Figure 1. Structure of the substrates
To look at the role of the solvent, in the intramolecular cycli-
sation of I, we carried out the copper (+2) perchlorate-mediated
reaction in a 1:1 mixed solvent of methanol and ethanol. From
this reaction only compound IV was obtained. To know the
source of the incorporated methoxy group in compound IV,
we carried out the copper (+2) perchlorate-mediated reaction
of I in deuterated methanol. The cyclic product IVa containing
the deuterium-labelled methoxy group (Scheme 3) was obtained
from this reaction. This shows the methanol-d4 solvent to be the
source of incorporated deuterated methoxy group. The mass
spectra of IV has m/e at 229.09 whereas the mass spectra of
IVa has m/e at 232.09 confirming the latter to have the CD3O
group. Furthermore, when compound VI was reacted with cop-
per (+2) perchlorate hexahydrate, in CD3OD we obtained com-
pound IVa (Scheme 3). This proves that in the case of copper
(+2) mediated reaction, first, the intramolecular nucleophilic sub-
stitution takes place to form a C–N bond, leading to product VI,
and it further reacted with methanol in the presence of copper
(+2) perchlorate to give product IV. The SRN1 mechanism for
coupling of nucleophile is well established in quinoline deriva-
tives.[35] Thus, it may be a methoxy radical that is introduced
via a C–H bond cleavage of VI to result into the formation of
IV, where the radical formation is initiated by the copper (+2)
ions. Copper (+2) ions are good for radical generation[36] by in-
terconversion to copper (+1). In the case of nickel, such redox
couple is absent, thus not leading to the incorporation of the
methoxy group. In a nutshell, copper (+2) ion resulted in
obtained via C–N and C–O bond formation reactions. When the
reaction was carried in ethanol with copper (+2) salts, cyclisation
of I was not observed, but compound V was formed by C–O
bond formation through nucleophilic substitution. It was also ob-
served that the intramolecular cyclisation reaction of I was pro-
moted by nickel (+2) salts and the compound VI was formed
in both methanol or ethanol. Thus, these reactions are highly
sensitive towards both metal ions and solvents. The solution of
I in methanol or ethanol do not give products alone but pres-
ence of stoichiometric amount of copper (+2) or nickel (+2) ions
in such solution gave the products within 2h. The counter anions
have roles in these reactions; the anions such as perchlorate and
nitrate were found to be suitable over ions like acetate, chloride
or bromide. In either case the cyclic product through C–C bond
formation as depicted in Scheme 1 was not formed. This is due
to the preference of forming a six-membered ring during C–N
bond formation over the five-membered ring that would have
formed in the case of C–C bond formation. The intramolecular
cyclisation reactions leading to heterocyclic rings are very com-
mon in organic chemistry[31–34] and preferences of formation
of thermodynamically favoured products are well documented.
The compound IV and VI have structural similarities, and the dif-
ference between them is a methoxy group. Thus, to show dis-
tinction of each product obtained from the reactions of I, the
1H-NMR spectra of the products IV, V and VI can be used. Some
M(ClO4)2
N
N
N
N
ClO4
ClO4
HN
O
O
HN
O
ROH
NH
NH
O
O
O
Br
VI
I
IV
V
% ratio of product IV : V : VI
M = Cu, R=CH3
;
100
0
0
0
M = Cu, R=CH3CH2
;
0
0
100
0
M = Ni, R=CH3CH2, CH3
;
100
Scheme 2. Synthesis of product IV, V, VI
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J. Phys. Org. Chem. 2012, 25 169–175

C–N BOND FORMATION REACTIONS OF QUINONLINE DERIVATIVES
involved in C–HÁÁÁO interactions (C12–H12AÁÁÁO2) with the oxy-
gen atoms of perchlorate anions. The self assembly of the com-
pound VI is shown in Fig. 2(b).
Ni(ClO4)2
CH3OH
Cu(ClO4)2
CD3OD
N
NH
We also studied the reaction of 2-bromo-N-(quinolin-8-yl)
acetamide (II) with nickel (+2) and copper (+2) salts in methanol
as well as in ethanol. In this case irrespective of metal ion, anion
or the solvent cyclised product through C–N bond formation was
observed (Scheme 4). Depending on the counter anion on the
metal salt used, the cyclic amides VIIa and VIIb were formed.
In the case of II, when acetone was used as solvent with primary
amines along with potassium carbonate, we could replace the
bromide ion to form nucleophilic products; however, in the case
of the substrate II we have not observed nucleophilic substitu-
tion of the bromide ion either by ethanol or methanol.
ClO4
O
VI
N
Cu(ClO4)2
CD3OD
ClO4
N
NH
HN
Br
O
O
CD3
O
I
IVa
Scheme 3. Formation of deuterium substituted product IVa
These results suggest that there is an initial coordination of
metal ion to the precursor I and II and as the bromide is ab-
stracted by metal, concomitant C–N bond formation takes place
to form a cation of three fused heterocyclic rings. In both cases
of copper and nickel ions the substitution is favoured by the co-
ordination effect. This coordination effect is not favourable in the
case of the substrate III; hence, we did not observe any nucleo-
philic substitution in III under ordinary conditions. The crystal
structure of compound VIIa (Fig. 3(a)) and VIIb (Fig. 4(a)) shows
that the same molecule adopts different structures with different
anions. Compound VIIa crystallises in the monoclinic space
group P2(1)/c whereas the compound VIIb crystallises in the or-
thorhombic space group Pnma. Previously, it has been estab-
lished that in quinoline-based compounds the host molecule
adopts a different structural orientation depending on the na-
ture of the guests.[29] Hence, this difference in structural orienta-
tion is attributed to the size and structure of the counter anion.
In the case of VIIa the counter ion is a perchlorate anion that is
of tetrahedral shape, and in the case of VIIb the counter ion is
a nitrate anion that is planar. Here, it is also observed that in
compound VIIa the whole cationic part of the molecule and
the perchlorate anion is present in the asymmetric unit (Fig. 3
(a)), whereas in the case of compound VIIb only one-half of
the molecule is present in the asymmetric unit (Fig. 4(b)).
The compound VIIa forms a one-dimensional chain with a C–
HÁÁÁO interaction (C4–H4ÁÁÁO1), which is further linked by another
C–HÁÁÁO interaction with the perchlorate anion (C8–H8ÁÁÁO2). The
two one-dimensional chains are further interlinked by a C–HÁÁÁO
interaction (C2–H2ÁÁÁO1) and a p–p interaction (C6–C6, 3.34 Å).
The self assembly formation of compound VIIa is shown in Fig. 3(b).
cyclisation followed by methoxy group incorporation to the
cyclised product. The conversion of I to IV was also monitored
by UV–Vis spectroscopy (please see supplementary materials).
The compound IV has absorption at 379nm, whereas the com-
pound I has no absorbance at this wavelength. It was observed
that the addition of copper (+2) perchlorate solution to a meth-
anol solution of I led to growth of absorption at 379nm because
of the formation of IV. From this UV–Vis study, however, we
could not monitor the formation of VI as an intermediate com-
pound; the compound VI has absorption at 395 nm but with
comparable extinction coefficient, and no observation of a peak
of VI in the visible spectra points out that the transformation of
VI to IV is fast. In the case of nickel the formation of VI could be
seen as this is the end product in that reaction.
The structural chemistry of quinoline derivatives is interesting
from molecular recognition[37] and from observation of multiple
numbers of symmetry nonequivalent molecules in unit cell.[29]
The structure of the compound VI is determined by X-ray crystal-
lography and is shown in Fig. 2(a). The compound VI crystallises
in monoclinic space group P2(1)/n. Its asymmetric unit comprises
of a cation of three fused heterocyclic rings and one perchlorate
anion. The molecules are self-assembled and the self-assembly is
governed by p–p interactions (C8–C4, 3.370Å) and C–HÁÁÁO inter-
actions (C6–H6ÁÁÁO1; C11–H11ÁÁÁO1). These interactions lead to
the arrangement of molecules in the form of one-dimensional
chain. The perchlorate anions are held between two such one-di-
mensional chains through C–HÁÁÁO (C4–H4ÁÁÁH4; C2–H2ÁÁÁO3) and
N–HÁÁÁO (N2–H2AÁÁÁO5) interactions. The two methyl groups are
projected away from each other and the methyl protons are
(a)
(b)
Figure 2. (a) ORTEP diagram of the compound VI (Drawn with 50% thermal ellipsoid). (b) Short range interactions in VI
J. Phys. Org. Chem. 2012, 25 169–175
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D. KALITA AND J. B. BARUAH
MX2
N
N
X
NH
HN
Br
O
Methanol or Ethanol
O
VIIa, whenM = Cu or Ni, X= NO3
VIIb, whenM = Cu or Ni, X= ClO4
II
Scheme 4. Synthesis of compounds VIIa and VIIb
(a)
(b)
Figure 3. (a) ORTEP diagram of the compound VIIa (drawn with 50% thermal ellipsoid). (b) Short range interactions in VIIa
The crystal structure of compound VIIb shows interesting
crystallographic features, the asymmetric unit contains only
one-half of the molecule even though the molecule is not
symmetric. It is observed that the two nitrogen atoms (N1 and
N2) and the two carbon atoms (C2 and C7) are disordered and
share a 50% electron density each as shown in Fig. 4(c). The
self-assembly of the compound VIIb is also governed by a
number of weak interactions such as C–HÁÁÁO (C3–H3ÁÁÁO2;
C5–H5ÁÁÁO1) and N–HÁÁÁO interaction (N2–HÁÁÁO3). These weak
interactions led to the formation of a two-dimensional wave-like
structure as shown in Fig. 4(a).
Quinoline-based receptors have been identified to be sensi-
tive to anion binding.[38–42] Thus, we have studied the absorp-
tion and emission of these compounds. The compound I
shows an absorbance maximum at 326nm whereas the com-
pounds IV, V and VI show an absorbance maximum at 316
nm. In addition to the peak at 316nm, the compounds IV, V
and VI show a peak at 379, 369 and 395nm, respectively. The
UV–Vis spectra are shown in Fig. 5(a). All these compounds are
fluorescence active except compound IV. The emission spectra
of compounds I, IV, V and VI are much different from each other
as shown in Fig. 5(b). Compound I shows an emission peak at
398nm upon excitation at 310nm (Fig. 5(b)). The fluorescence
emission intensity is very weak for compound IV (Fig. 5(b)); how-
ever, the compound V shows an intense emission peak at 375
nm upon excitation at 310nm (Fig. 5(b)). Unlike the other com-
pounds, VI shows an emission peak in a much different region,
that is, at 463nm upon excitation at the same wavelength (Fig. 5
(b)). The large difference in fluorescence emission of V and VI
occurs because of the difference in structures. This point is im-
portant as nickel (+2) and copper (+2) ion can be distinguished
from the fluorescence emission by using this property. Second,
the compound IV has a very weak fluorescence than V and at
a different wavelength; this can indirectly distinguish the two
solvents methanol and ethanol.
The compounds II, VIIa and VIIb show absorbance maximum
at 316nm (Fig. 6(a)). In addition to a peak at 316nm, compound
II shows an absorbance peak at 373nm whereas both compound
VIIa and VIIb show absorbance at 386 nm. This shows that there
is a 13-nm shift in the absorbance on the formation of cyclised
perchlorate or nitrate salt. This also shows that the anion does
not cause change in the absorption spectra of these products.
All the compounds II, VIIa and VIIb are fluorescence active; sim-
ilar to the UV spectra the emission spectra of the products (VIIa
and VIIb) are different from the starting material (II). Compound
II shows an emission peak at 497 nm upon excitation at 380nm,
whereas both the compounds VIIa and VIIb show an emission
peak at 510nm upon excitation at 380nm. The emission spectra
are shown in Fig. 6(b). Thus, the trend in change in fluorescence
emission is similar to the absorption spectra, that is, cyclised pro-
ducts have an emission at higher wavelength with enhancement
of intensity.
In conclusion, C–N bond formation leading to intramolecular
cyclisation reactions of I and II are facilitated by copper (+2)
and nickel (+2) ions. The copper(+2) mediated intramolecular
cyclisation reactions are substrate dependent. In the case of I
the initially formed cyclised product further undergoes C–H acti-
vation to give OMe-substituted derivative in methanol. The same
reaction in ethanol replaces bromide with ethoxide, without for-
mation of a cyclic product. Nickel(+2) mediated reactions invari-
ably led to the formation of a cyclic product through C–N bond
formation. Thus, in the case of copper, multiple mechanisms in-
volving cation and radical are favoured, whereas in the case of
nickel it is an ionic mechanism leading to anion exchange.
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J. Phys. Org. Chem. 2012, 25 169–175

C–N BOND FORMATION REACTIONS OF QUINONLINE DERIVATIVES
(a)
(b)
(c)
Figure 4. (a) Structure of VIIb (C, N atoms are disordered); (b) ORTEP diagram of the asymmetric unit of compound VIIb (Drawn with 50% thermal
ellipsoid); and (c) short range interactions in VIIb
(a)
(b)
Figure 5. (a) UV–Vis spectra of (1) compound I; (2) compound IV; (3) compound VI and (4) compound V; (b) Emission spectra (lex=310nm) of (1) com-
pound I; (2) compound IV; (3) compound VI and (4) compound V. (In all cases methanolic solution 6.6Â10–5M were used)
Furthermore, the three fused heterocyclic rings described here
are fluorescence active. The chemical reactivity differences can
EXPERIMENTAL
be used as a tool to distinguish the solvents as well as metal ions
because the fluorescence emission of each product differs. Palla-
dium (+2) acetate causes intramolecular cyclisation of II without
anion exchange.
The compounds I and II were synthesised by the reported proce-
dure [43]. Caution: The perchlorate salts are potentially explosive
and should be handled with care in limited amounts. However,
no such observations by us in the present experiments in 1mmol
J. Phys. Org. Chem. 2012, 25 169–175
Copyright # 2011 John Wiley & Sons, Ltd.
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D. KALITA AND J. B. BARUAH
(b)
(a)
Figure 6. (a) UV–Vis spectra of (1) compound VIIa, (2) compound VIIb and (3) compound II. (b) Emission spectra (lex=380nm) of (1) compound VIIa,
(2) compound VIIb and (3) compound II. (In all cases methanolic solution 6.6Â10–5M were used)
scale were observed. Nevertheless, they should be handled with
care and such reactions are to be carried under a fume cupboard.
164.9. LC-MS [M–1]: calculated for C14H15N2O2 243.1134; found
243.1302. Vis: (Methanol, lmax) 369 nm (e=8.45Â103M–1cm–1).
Synthesis of 2-bromo-N-(quinolin-5-yl) acetamide (III)
Synthesis of compound (VI)
The compound was synthesised by a procedure similar to II; the
difference was the use of 5-aminoquinoline in place of 8-amino-
quinoline. Yield: 72%. IR (KBr, cm-1): 3446 (bs), 3019 (m), 1689 (s),
1629 (s), 1596 (m), 1560 (m), 1537 (s), 1408 (m), 1369 (s), 1287 (s),
2-Bromo-N-(quinolin-8-yl) propanamide (I) (1mmol, 0.28g) was
dissolved in methanol (15ml) and nickel (+2) perchlorate hexa-
hydrate (1mmol, 0.365g) was added. The solution was stirred
for 40 min at room temperature and kept undisturbed. Brown-
coloured crystals of compound VI were observed after 3 days.
The solution was then filtered to isolate the product. Yield:
71%. IR (KBr, cm–1): 3424 (bs), 3043 (m), 2903 (w), 1694 (s),
1607 (w), 1587 (w), 1542 (m), 1492 (w), 1422 (m), 1392(m), 1365
(m), 1241 (w), 1140 (s), 1116 (s), 1078 (s), 835 (m), 760 (w), 624
(m). 1H-NMR (DMSO-d6, 400MHz): 11.8 (s, 1H); 9.5 (s, 1H); 9.2
(d, 1H, J=7.6Hz); 8.2 (d, 1H, J=5.2Hz); 8.0(m, 2H); 7.5 (d, 1H, J=
6.8Hz); 5.8 (m, 1H); 1.8 (s, 3H). 13C-NMR (DMSO-d6, 100MHz):
24.1, 63.5, 118.3, 123.1, 124.0, 125.9, 130.2, 130.6, 131.4, 147.3,
147.6, 164.9. LC-MS [M+]: calculated for C12H11N2O 199.08 found
199.03. Vis: (Methanol, lmax) 395 nm (e=4.72Â103M–1cm–1).
6
1235 (m), 1116 (w), 912 (w), 813 (s), 695 (m). 1H-NMR (DMSO-d ,
400MHz): 11.0 (1H, s); 9.5 (1H, d, J=8.4Hz); 9.3 (1H, d, J=5.2Hz);
8.2 (2H, d, J=6.8Hz); 8.0 (2H, m); 4.3 (2H, s). 13C-NMR (DMSO-d6,
100MHz): 29.2, 117.4, 120.8, 123.8, 135.0, 138.1, 143.0, 144.1,
166.6. LC-MS [M+]: calculated for C11H9BrN2O 264.9932; found
265.0150.
Synthesis of compound (IV)
2-Bromo-N-(quinolin-8-yl) propanamide (I) (1mmol, 0.28 g) was
dissolved in methanol (15 ml) and copper (+2) perchlorate hexa-
hydrate (1mmol, 0.370 g) was added. The solution was then
stirred for 30 min in room temperature and kept undisturbed.
Brown-coloured crystals of compound IV were observed after 4
days. The solution was then filtered and the product was isolated.
Yield: 47%. IR (KBr, cm–1): 3433 (bs), 3006 (m), 2934 (w), 2890 (w),
2853 (m), 1704 (s), 1583 (w), 1545 (m), 1495 (w), 1469 (m), 1390
(m), 1275 (w), 1229 (m), 1174 (m), 1143 (s), 1114 (s), 1086 (s),
Synthesis of compound (VIIa)
2-Bromo-N-(quinolin-8-yl) acetamide (II) (1mmol, 0.26g) was dis-
solved in methanol (15ml) and copper (+2) nitrate tetrahydrate
trihydrate (1mmol, 0.24g) was added. The solution was stirred
for 30min at room temperature and kept undisturbed. Brown-
coloured crystals of compound VIIa were observed after 3 days.
A similar reaction performed with nickel (+2) nitrate resulted in
compound VIIa. Yield: 72%. IR (KBr, cm–1): 3434 (bm), 3043 (m),
3013 (m), 2929 (m), 2852 (w), 1698 (s), 1584 (m), 1543 (m),
1491 (w), 1384 (s), 1239 (w), 1154 (w), 1130 (w), 839 (m), 795
1
839 (m), 625 (m). H-NMR (DMSO-d6, 400MHz): 12.3 (s, 1H); 9.6
(d, 1H, J=5.6Hz); 9.3 (d, 1H, J=8.0Hz); 8.3 (d, 1H, J=6.0Hz); 8.1
(d, 1H, J=8.0Hz), 7.9 (t, 1H, J=8.0Hz); 7.6 (d, 1H, J=7.2Hz); 3.5
(s, 3H); 1.9 (s, 3H). 13C-NMR (DMSO-d6, 100MHz): 23.7, 48.8,
63.2, 118.0, 122.8, 123.6, 125.5, 129.9, 130.3, 131.0, 147.0, 147.3,
164.5. LC-MS [M+]: calculated for C13H13N2O2 229.0977; found
229.0975. Vis: (Methanol, lmax) 379nm (e=4.64Â103M–1cm–1).
1
(w), 754 (w), 526 (w). H-NMR (DMSO-d6, 400MHz) : 11.8 (s, 1H);
9.2 (d, 1H, J=6.0Hz); 9.1 (d, 1H, J=8.4Hz); 8.2 (t, 1H, J=6.0Hz);
7.9 (m, 2H); 7.5 (d, 1H, J=7.2Hz); 5.6 (s, 2H). 13C-NMR
(DMSO-s6, 100MHz): 56.2, 118.1, 122.8, 123.5, 126.7, 130.0,
131.4, 147.2, 147.7, 161.6. LC-MS [M+]: calculated for C11H9N2O
Synthesis of compound (V)
Compound V was synthesised by a procedure similar to com-
pound IV, except that in this case ethanol was used as solvent
instead of methanol. Yield: 63%. IR (KBr, cm–1): 3444 (bs), 1627
(s), 1501(m), 1467 (m), 1399 (m), 1121 (w), 1086 (w), 829 (w),
185.0715; found 185.0626. Vis: (Methanol, lmax
) 386 nm
(e=1.02Â104M–1cm–1).
Synthesis of compound (VIIb)
1
788 (w), 636 (w). H-NMR (DMSO-d6, 400MHz): 11.8 (s, 1H); 9.5
(d, 1H, J=5.6Hz); 9.2 (d, 1H, J=8.4Hz); 8.2 (t, 1H, J=6.0Hz); 8.0
(d, 1H, J=8.4Hz); 7.9 (t, 1H, J=7.6 Hz); 7.6 (d, 1H, J=7.6 Hz); 5.8
(q, 1H, J=7.2 Hz); 3.4 (m, 2H); 1.8 (d, 3H, J=7.6 Hz); 1.0
(t, 3H, J=8.8 Hz). 13C-NMR (DMSO-d6, 100MHz): 19.1, 24.1, 56.7,
63.5, 118.3, 123.2, 124.1, 125.9, 130.2, 130.7, 131.4, 147.3, 147.7,
A similar synthetic procedure to VIIa was used for the synthesis
of compound VIIb, the only difference is that in this case copper
(+2) perchlorate hexahydrate was used instead of copper (+2)
nitrate trihydrate. The reaction was also performed with nickel
(+2) perchlorate; resulted in compound VIIb. Yield: 74%. IR (KBr,
wileyonlinelibrary.com/journal/poc
Copyright # 2011 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2012, 25 169–175

C–N BOND FORMATION REACTIONS OF QUINONLINE DERIVATIVES
cm–1): 3433 (bm), 3013 (m), 2928 (m), 2852 (m), 1698 (s), 1607
(w), 1584 (m), 1543 (s), 1428 (m), 1417 (m), 1385 (s), 1298 (w),
1240 (m), 1144 (s), 1115 (s), 1079 (s), 909 (w), 838 (m), 754 (m),
624 (m). Vis: (methanol, lmax) 386nm (e=1.60Â103M–1cm–1).
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