An insight into the extraction of transition metal ions by picolinamides associated with intramolecular hydrogen bonding and rotational isomerization

Article abstract of DOI:10.1039/c4ra02030h

The clear connection between molecular structures of N-substituted picolinamides and extraction behaviour has been rationalized by highlighting the relationship between intramolecular hydrogen bonding and rotational isomerism. To this aim aromatic pyridine-2,6-dicarboxamides 1a-1c with N-substitution and their analogues 3a and 3b containing intramolecular hydrogen bonds were designed and synthesized. The results from the liquid-liquid extraction towards some representative transition metal picrates including Ag⁺, Hg ²⁺, Pb²⁺, Cd²⁺, Zn²⁺, Cu ²⁺, Co²⁺ and Ni²⁺ salts demonstrated that the higher selectivity and efficiency towards Hg²⁺ (88.6-95.4%) over other metal cations stem mainly from N-substitution via disruption of intramolecular H-bonding. X-ray structural analysis, and ordinary and variable-temperature proton and carbon NMR experiments provided supporting information for expounding the difference in extraction ability among these ligands, particularly the importance of N-substitution that leads to the formation of rotamers affecting the extraction process.

Full text of DOI:10.1039/c4ra02030h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
An insight into the extraction of transition metal
ions by picolinamides associated with
intramolecular hydrogen bonding and rotational
isomerization†
Cite this: RSC Adv., 2014, 4, 29702
a
a
a
a
a
b
*
Yan Li, Yiming Jia, Zhenwen Wang, Xianghui Li, Wen Feng, Pengchi Deng
a
*
and Lihua Yuan
The clear connection between molecular structures of N-substituted picolinamides and extraction
behaviour has been rationalized by highlighting the relationship between intramolecular hydrogen
bonding and rotational isomerism. To this aim aromatic pyridine-2,6-dicarboxamides 1a–1c with
N-substitution and their analogues 3a and 3b containing intramolecular hydrogen bonds were designed
and synthesized. The results from the liquid–liquid extraction towards some representative transition
metal picrates including Ag+, Hg2+, Pb2+, Cd2+, Zn2+, Cu2+, Co2+ and Ni2+ salts demonstrated that the
higher selectivity and efficiency towards Hg2+ (88.6–95.4%) over other metal cations stem mainly from
N-substitution via disruption of intramolecular H-bonding. X-ray structural analysis, and ordinary and
variable-temperature proton and carbon NMR experiments provided supporting information for
expounding the difference in extraction ability among these ligands, particularly the importance of
N-substitution that leads to the formation of rotamers affecting the extraction process.
Received 8th March 2014
Accepted 19th June 2014
DOI: 10.1039/c4ra02030h
www.rsc.org/advances
or complexes, were found to involve in interacting or coordi-
nating with metal ions in synergy with the nitrogen of pyridine
moiety.9,11 It has been noted that substitution on nitrogen of
Introduction
Amide-based compounds and their corresponding metal
complexes have been widely investigated due to the easy
synthesis of ligands, high resistance to hydrolysis, and potential
coordination ability of amide hydrogen and/or oxygens.1 These
features render them nd applications as extractants in sepa-
ration technology,2 sensors in detecting metal ions,3 and
building blocks for constructing architectures in catalysis.4
Diglycolamides,5 pyridine-modied calixarenes,6 CMPO-tripo-
dands,7 and pyridine dicarboxyamides8 are examples of extrac-
tion systems that have demonstrated higher separation
efficiency in discriminating lanthanides/actinides (Ln/Ac)
elements. Among them, pyridine-based carboxyamides or
dicarboxyamides and their analogues represent a class of
ligands that have attracted attention in forming metal
complexes9 and in use for metal separation.8,10 The amide
linkages, as part of the molecular constituents of these ligands
amide bonds of synthetic ligands led to improved performance
in two-phase extraction of lanthanides/actinides elements.12 In
fact, the effect of N-substituted ligands upon the extraction and
separation efficiency had been observed in diamide systems ca.
two decades before.13 However, the reason behind it is still not
clearly claried. For 2,6-dicarboxypyridine diamides, the
explanation was limited to the electronic and steric effects that
may dominate the atoms coordinating to the metal center in.14
It was known that hydrogen bonding formation involving
amide groups contribute a great deal to the construction of
complex natural and articial supramolecular assemblies.15
Incorporation of hydrogen bond (H-bond) groups into ligands
was able to orient incoming groups or stabilize metal–ligand
adducts.16 Besides the importance of metal complexing sites
associated with amide linkage for effecting the separation
process, intra- or intermolecular hydrogen bonding contained
in the molecular structure of a ligand may also play a role in
governing the extraction efficiency and selectivity. However, this
aspect has scarcely been explored to date. We recently employed
hydrogen bonded aromatic oligoamides with backbones pre-
organized by aid of intramolecular three-center hydrogen bonds
for solvent extraction separation of transition metal ions.17 The
importance of intramolecular hydrogen bonding present in
these compounds was also demonstrated by the formation of
aCollege of Chemistry, Key Laboratory for Radiation Physics and Technology of
Ministry of Education, Institute of Nuclear Science and Technology, Sichuan
University, Chengdu 610064, China. E-mail: lhyuan@scu.edu.cn; Fax: +86-28-
85418755; Tel: +86-28-85416996
bAnalytical & Testing Center, Sichuan University, Chengdu 610064, China. E-mail:
pcdeng@yahoo.com
† Electronic supplementary information (ESI) available: Characterization details,
extraction data. CCDC 990530 and 990531. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c4ra02030h
29702 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
their corresponding cyclo[6]aramides18 and efficiency in (see ESI†). Thus, the most likely possibility is the presence of
extraction towards Ln/An elements.19 Based on similar pre- rotational isomers for 1a since rotation around the amide
organization-induced folding mechanism, their higher bonds are considerably hindered upon introducing an ethyl
aromatic amide polymers also exhibited selective extraction of group onto the amidic nitrogen. In other words, it is the coex-
thorium(IV) and rare earth elements.20 Very recently, we revealed istence of several conformational isomers that caused the
that the subtle change of the coordination environment made complexity of its NMR spectrum. This led to the design of
by local intramolecular H-bonding of CMPO-modied calixar- compound 3a without substitution on nitrogen atoms. At the
enes led to selective separation of light/heavy lanthanides and same time, propoxy groups in 3a are placed at ortho-position
group separation between lanthanides and thorium/uranium.21 adjacent to the amide bond to allow formation of intra-
Despite much progress made in using 2,6-pyridine dicarboxy- molecular hydrogen bonds, thus partially rigidifying the back-
amides as solvent extractants22 and the well-known fact for the bone of the molecule (vide post). Free rotation around nitrogen
formation of amide rotamers,23 surprisingly, the correlation of the amide NH and carbon of the phenyl ring is expected to be
between the presence of intramolecular hydrogen bonding impossible. Compound 3b, which bears the same backbone
associated with amide NH in effecting liquid–liquid extraction with ortho-substituted methyl group, is designed to see if partial
behaviour and rotational isomerization is still unexplored.
hydrogen bonding is still strong enough to maintain the
With our continued interest in amide-based compounds and molecular conformation as 3a. Positional isomers 1b and 1c are
macrocyclic compounds for metal ion separation,24 we report also designed for comparison. Given the importance of coor-
herein on the exploration of intramolecular hydrogen bonding dination directionality in forming extractive species, it can be
in regulating extraction process pertinent to rotational isom- envisioned that if the orientation of carbonyl oxygen atoms is
erism by N-substitution using a series of synthesized picolina- manipulated by the presence of hydrogen bonding to restrict
mides. Transition metal ions including Ag+, Hg2+, Pb2+, Cd2+, the amide rotations, different extraction behaviour should
Zn2+, Cu2+, Co2+, Ni2+ were selected to assess the outcome due to result.
structural alternation of ligands used in the liquid–liquid
extraction experiments.
Synthesis and solid state structures
Typically all 2,6-pyridine dicarboxyamides 1a–1c, 2, 3a and 3b
Results and discussion
were synthesized based on the coupling reactions of acyl chlo-
Initial consideration and molecular design
rides and corresponding anilines according to Scheme 1. All of
these compounds were characterized by 1H NMR, 13C NMR and
Picolinamides 1–3 were used in the present study (Scheme 1).
HRMS. Compound 2 was prepared according to the reported
procedure.25a
Initially compound 1a bearing alkoxy substituents was designed
as a control for ligand 2 in comparing extraction of transition
metal ions. Compound 2 was reported to be potential extractant
for minor actinides25 and palladium separation.26 Interestingly,
The key precursors 5a–5c were obtained by reaction of
commercially available hydroxyl group-substituted nitroben-
zene and propyl bromide in the presence of K2CO3. The
syntheses of 6a–6c were carried out employing MeCN as ethyl-
ation agent.27 Treating the N-alkylated aniline derivatives 6a–6c
with 4 resulted in 1a, 1b, and 1c in overall isolated yields of 82%,
92% and 88%, respectively. Compound 3a was readily prepared
in 81% yield via two steps from hydrogenation of 5a with Pd/C
as catalyst to afford 7, followed by coupling of 2,6-pyr-
idinedicarbonyl dichloride 4.
1
examination of H NMR spectrum of 1a showed a complicated
pattern comprising several sets of signals that cannot be
designated as a pure component. However, a base peak at m/z
490.2701 corresponding to the most abundant species [M + H]+
in HRMS spectrum and a single peak from HPLC experiments
excluded the possibility of the presence of any other impurities
Single crystals of ligands 1a and 3a were obtained by slow
evaporation of a solution of CH2Cl2/n-hexane and ethyl acetate/
n-hexane at room temperature, respectively. Selected bond
lengths and angles for the two ligands from X-ray diffraction
experiment are given in Table 1.
Fig. 1a shows a view of the molecular structure of 1a. The
molecule of 1a has a C2 symmetry, and the C2 axis passes
through atoms C1 and N1 of the pyridine ring. The atoms of the
amide groups and those connected to amide carbon and
nitrogen (O1, C3, C4, N2, C5 and C7) are almost in a plane. The
˚
mean deviation from plane is 0.0401 A. In addition, the bond
angles across the amide nitrogen, C4–N2–C5, C4–N2–C7 and
C5–N2–C7 are all approximately 120ꢀ. These data suggest the
sp2 hybridization of the amide nitrogens N2, and the consid-
erable double bond character for the OC–N amide bonds.11a,28
So far as the arrangement of amide nitrogen relative to pyridine
Scheme 1 Synthesis of 2,6-pyridine dicarboxyamides 1a–1c, 2,25a 3a
and 3b.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29703

View Article Online
RSC Advances
Paper
Table 1 Selected bond lengths (Ǻ) and angles (ꢀ) for 1a and 3a
from each other with a dihedral angle of 75.65(4)ꢀ. The orien-
tation of the phenyl group is designated as E (trans) relative to
the carbonyl oxygens when the OC–N amide bond is considered
as a double bond. Consequently, 1a adopts E–anti–anti–E
conformation (also see Scheme 2a, blue). The dihedral angle
between the pyridine ring and each of the two phenyl groups
(C7–C8–C9–C10–C11–C12) is 65.04(7)ꢀ.
For 3a, the solid state structure clearly indicates the presence
of two intramolecular three-center hydrogen bonds, N2/H1/
O1 and N2/H3/O4, each comprising two ve-membered
rings to x the molecule in a crescent fashion as shown in
Fig. 1b. The parameters of H-bonds involving in 3a are shown in
Table 2. The H-bond lengths of N2/H1, O1/H1, N2/H3 and
Bond lengths (Ǻ)
Bond angles (ꢀ)
1a
3a
C3–C4
O1–C4
N2–C4
N2–C5
N2–C7
1.510(5)
C3–C4–O1
C3–C4–N2
O1–C4–N2
C4–N2–C5
C4–N2–C7
119.82(5)
117.63(2)
122.53(2)
119.12(8)
122.92(6)
117.57(7)
121.75(7)
113.35(3)
124.89(0)
116.28(5)
127.52(0)
116.19(5)
122.05(9)
113.68(6)
124.25(2)
115.96(5)
128.08(5)
115.95(0)
1.222(7)
1.349(0)
1.474(5)
1.431(5)
C5–N2–C7
C10–C11
C10–O2
C10–N1
N1–H1
1.507(8)
1.218(6)
1.347(6)
0.859(7)
1.408(2)
1.499(8)
1.211(2)
1.351(2)
0.859(8)
1.404(5)
C11–C10–O2
C11–C10–N1
O2–C10–N1
C10–N1–H1
C10–N1–C9
H1–N1–C9
C15–C16–O3
C15–C16–N3
O3–C16–N3
C16–N3–H3
C16–N3–C17
H3–N3–C17
N1–C9
C16–C15
C16–O3
C16–N3
N3–H3
˚
˚
˚
˚
O4/H3 are 2.219(7) A, 2.277(6) A, 2.223(5) A and 2.254(9) A,
respectively, suggesting the formation of strong H-bonds. Two
additional weak hydrogen bonds O2/H8 and O3/H18 are also
N3–C17
observed,29 the lengths of which are 2.464(5) A and 2.424(0) A,
respectively. The dihedral angles between the pyridine ring and
phenyl groups C4–C5–C6–C7–C8–C9 (phenyl 1) and C17–C18–
C19–C20–C21–C22 (phenyl 2) are 32.43(4)ꢀ and 25.46(4)ꢀ,
respectively. It is worth noting that the two intramolecular
three-center H-bonds are twisted and not in the same plane due
to the steric crowding between the two adjacent propoxy groups.
As in 1a, the two amide nitrogens in 3a are also sp2 hybridized
for the bond angles across each of the two amide nitrogens N1
and N3 are ca. 120ꢀ and the mean deviations of the two amide
group C9–N1–H1–C10–O2–C11 (plane 1) and C15–C16–O3–N3–
H3–C17 (plane 2) are 0.0341 and 0.0417, respectively. The
dihedral angles between the pyridine ring and the amide groups
plane 1 and plane 2 are 5.39(1)ꢀ and 2.46(3)ꢀ, respectively.
˚
˚
A
similar compound with methoxy groups, N,N0-bis-
(2-methoxyphenyl)pyridine-2,6-dicarboxamide, gave a crystal
structure analogous to 3a where two three-center H-bonds were
also observed.29a
Intramolecular hydrogen bonds (H-bonds) in solution
Infrared spectrum could only provide evidence of hydrogen
bond of 3 in CHCl3 (see ESI, Fig. S24 and S26†), but it is
impossible to distinguish intramolecular from intermolecular
hydrogen bonding interactions. The bands due to hydrogen
bonded NH stretching of 3a and 3b were found to shi towards
lower wavenumber of respective 3372 and 3397 cmꢁ1 compared
to higher wavenumber of more than 3400 cmꢁ1 of common free
amide NH.30a Thus, to verify the presence of intramolecular H-
bonds in picolinamides 3 without N-substitution, the temper-
ature coefficients ddH/dT of N–H were determined in the
temperature range between 298 K to 333 K (in steps of 5 K) in
Fig. 1 The crystal structures of (a) 1a and (b) 3a. Hydrogen atoms are
omitted for the sake of clarity except for those forming hydrogen
bonds.
1
CDCl3 or DMSO-d6/CDCl3 (2/8, v/v) by variable-temperature H
NMR experiments (Fig. 2). It is generally accepted that in
nonpolar solvents when the coefficient is less negative than ꢁ3
nitrogen is concerned, the crystal structure of 1a reveals the ppb Kꢁ1, the hydrogen bonding interaction is considered as
anti–anti conformation: both of the amide nitrogens placed in intramolecular; when it is more negative than ꢁ5 ppb Kꢁ1, it is
trans position with respect to pyridine nitrogen. The dihedral taken as intermolecular hydrogen bond.30 The ddH/dT of N–H in
angle between the pyridine ring and each of the amide planes is 3a was measured to be ꢁ1.58 ppb Kꢁ1 in DMSO-d6/CDCl3 (2/8, v/
64.99(5)ꢀ. To avoid n–n repulsion between the lone pairs of v), which shows a small variation with temperature. This
carbonyl oxygens, the two amide planes are staggered away suggests the high possibility of the presence of intramolecular
29704 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Scheme 2 Conformational conversion of isomers (a)–(c): (a) rotamer interconversion from 1a; (b) conformer formation of 3a via intramolecular
H-bonding; (c) conformer formation of 3b via intramolecular H-bonding. (d) Conformation of compounds 2 (ref. 11a) and 9 (ref. 35) in solid state.
H-bonds even in a polar solvent.31 Therefore, these results are in
Table 2 The parameters of H-bonds involving in 3a
accord with the observation of presence of intramolecular H-
:D–H/A/ꢀ
˚
D
H
A
d(H/A)/A
bonds in the crystal structure of 3a. For 3b, the ddH/dT of N–H
was measured to be ꢁ1.62 ppb Kꢁ1 in nonpolar CDCl3 and
ꢁ5.71 ppb Kꢁ1 in polar solvent DMSO-d6/CDCl3 (2/8, v/v). The
small variation of ddH/dT in nonpolar solvent also discloses the
presence of intramolecular H-bonds in 3b. Both of the infrared
spectra and temperature coefficients data indicate that the two-
center hydrogen bonds in 3b are less stable than the three-
center hydrogen bonds in 3a.
N1
N1
N3
N3
C8
H1
H1
H3
H3
H8
H18
N2
O1
N2
O4
O2
O3
2.219(7)
2.277(6)
2.223(5)
2.254(9)
2.464(5)
2.424(0)
111.59(1)
101.14(1)
111.30(9)
103.11(2)
112.99(0)
114.78(2)
C18
Rotational isomerization
Comparison of the 1H NMR spectra of compounds 1a–1c and 3a
or 3b disclosed a signicant difference in complicacy of signal
patterns and chemical shis of protons b and a on the pyridine
moiety (Fig. 3).
Among the three positional isomers 1a–1c, 1a exhibits the
most poorly-resolved signals over the full spectrum (Fig. 3a). We
exclude the possibility of contamination of impurities by HPLC
and MS detection (see ESI†). Compound 2, a well-known
extractant25,26 with N-ethylated substituent, but free of any
replacement on benzene ring, showed similar indistinguishable
signals (see ESI†). In stark contrast, 1c, which bears a propoxy
group at para-position, provided a much “clean” spectrum with
distinguishable signals for almost all aromatic and aliphatic
protons a ꢂ i (Fig. 3c). Apart from the major clear signals, there
are some signals of very low intensity, suggestive of the presence
of other rotational isomers. For 1b, the situation sits in between
1a and 1c (Fig. 3b). Signals of each proton from various
Fig. 2 Chemical shifts of NH in 3a/3b versus temperature in DMSO-
d6/CDCl3 (2/8, v/v) or CDCl3 (600 MHz, 298 K to 333 K).
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29705

View Article Online
RSC Advances
Paper
across the full spectrum that could be detected (Fig. 4a), sug-
gesting the presence of a mixture of several major and minor
rotamers in solution. This is consistent with the observation of
1
several sets of indistinct H NMR signals (Fig. 3a). With 1b, a
structural isomer of 1a with propoxy groups at meta-position of
the benzene ring, the number of signals in 13C NMR spectrum is
drastically decreased to only 15, but some of the signals are
broad (Fig. 4b). Compound 1c, which bears a para-substituent,
gives a spectrum containing only 13 signals along with another
set of very weak signals (Fig. 4c). The decreased number of
signals from 13C NMR data suggests that the rotational barrier
decreases with change of substituents from ortho to meta to para
position. This is different from the result from 3a and 3b where
only well-resolved 13 and 11 signals were observed (Fig. 4d and
e), respectively, corresponding exactly to respective 25 and 23
carbons in the molecules due to their shape-persistency of
molecular backbone rigidied by intramolecular hydrogen
bonds. These results agree well with those from 1H NMR
spectra. Given the fact that the formation of rotamers is caused
by the limitation of CO–N bond rotation, reduction of steric
hindrance via alternation of substitution position would lead to
decreased rotational barrier and thus simple NMR patterns.
Indeed, as the steric hindrance between alkoxyphenyl group
and N–Et group increases with the substitution position in
order of ortho > meta > para, the signals in both 13C and 1H NMR
change from complex to simple and well-resolved.
Fig. 3 1H NMR spectra of compounds (a) 1a, (b) 1b, (c) 1c, (d) 3a and (e)
3b in CDCl3 (400 MHz, 298 K). Sign “*” represents signals of solvents.
To further probe rotational isomerization, variable-temper-
rotamers of 1b show a tendency to coalesce together but are ature NMR spectra were recorded using DMSO-d6 solutions of
broad. If compared to the clear, well-resolved signals for 3a 1a as a typical example in the temperature range from 298 K to
(Fig. 3d), these observations strongly suggest that the spectral 428 K (in steps of 10 K) for 1H NMR and 298 K to 418 K (in steps
complexity of 1a is more likely to arise from the concurrent of 20 K) for 13C NMR. In 1H NMR spectra (Fig. 5), each proton of
rotamers, rotational isomers that result from the hindered 1a presents complicated multiple sets of signals resulting from
rotations about OC–N bonds and N (amide)–C (Ph).23b,32 It various rotamers in solution at 298 K. Owning to the over-
should be noted that the molecular skeleton of 3a is preor- lapping of signals, it is difficult to identify the species and
ganized by aid of intramolecular three-center hydrogen bonds calculate equilibrium ratio for the rotamer mixture. With the
to take a crescent conformation. The two localized intra- increase of temperature, all the signals in 1a coalesce from
molecular hydrogen bonds each consist of two S(5)-type rings complex to broad into a set of distinguishable signals at
that involve the backbone amide hydrogen. It has been well approximate 408 K. In 13C NMR spectra (Fig. 6), the number of
established that this three-center hydrogen bond is highly the signals of 1a decreased from 29 at 298 K to 15 at about 398 K
stable, the presence of which hinders the rotational freedom of due to coalescence effect. Based on the overall change from
the aromatic amide-based backbones.33 Therefore, the shape- both 1H NMR and 13C NMR, the coalescence temperature for 1a
persistency endows the molecule of 3a with drastically-reduced is reasonably set at approximately 408 K. It is not possible to
rotation with respect to 1a–1c in solution, leading to an indi- calculate the temperature coefficients and the free energy,
1
cation of presence of only one species in solution in H NMR enthalpy and entropy of activation for the interconversion
spectrum. Furthermore, the rigid backbone also renders the between each rotamers by Eyring analysis because of the
1
preorganized carbonyl oxygen atoms of the molecule point complexity of H NMR in 1a.
outwards in 3a. Similarly, the presence of two intramolecular
To clearly describe rotational isomerization, conformation
hydrogen bonds in 3b also enforces globally curved conforma- designation is denoted by Z, E, syn and anti, respectively (vide
tion of the molecular backbone,23b,34 thus hindering the rotation supra). For 1a, there should exist about ten typical rotational
about OC–N amide bond as manifested in its clear proton isomers theoretically due to the blocked rotations about the
signals (Fig. 3e).
OC–N amide bonds and OC–C (pyridine) bonds (Scheme 2a),
The difference of 13C NMR spectra (Fig. 4) among 1a–1c, 3a which explains undistinguished signals on the NMR timescale.
and 3b was also observed. If there is no presence of rotational The molecular structure of 1a in the solid state conrms the
isomers in 1a–1c, with the molecular formula C29H35N3O4, the exclusive formation of the E–anti–anti–E isomer. The two amide
number of signals should be equal to or less than 15 due to their nitrogens are in anti conformation with respect to pyridine
structural symmetry. In fact, there are totally 29 strong signals nitrogen. This is quite different from the solid state structure of
in 13C NMR spectrum of 1a along with some very weak signals the previously reported analogue 2 (ref. 11a) or 9 (ref. 35)
29706 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Fig. 4 13C NMR spectra of compounds (a) 1a, (b) 1b, (c) 1c, (d) 3a and (e) 3b in CDCl3 (100 MHz, 298 K). Red and blue arrows represent some of
the major and minor rotational isomers, respectively.
bearing no substituents where the E–anti–syn–E conformation combinations: anti–Z, anti–E, syn–Z, and syn–E, from which only
was observed (Scheme 2d). In both cases of 1a and 2 (or 9), the E six reasonable conformations E–syn–syn–E, E–anti–syn–E, E–
conformation as designated around amide bond is mainly anti–anti–E, E–anti–syn–Z, E–syn–syn–Z, Z–syn–syn–Z were
attributed to the outcome of n–p repulsion, i.e., electronic obtained (Fig. 7). In the anti–Z conformation, carbonyl oxygen
repulsion between the electron-dense center of the amide atoms experience both n–n repulsion with the pyridine nitrogen
oxygen and the phenyl ring.28c,36 Computer modeling37 disclosed and n–p repulsion with the phenyl ring, leading to much lower
the higher energy for anti–Z conformation among four possible stability of the conformation. Thus, the observed E–anti–anti–E
Fig. 5 Temperature dependent 1H NMR spectra of 1a in DMSO-d6 in the range from 298 K to 428 K (600 MHz).
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29707

View Article Online
RSC Advances
Paper
Fig. 6 Temperature dependent 13C NMR spectra of 1a in DMSO-d6 in the range from 298 K to 418 K (150 MHz).
Cu2+. Ligand 1a extracted almost exclusively Hg2+ compared to
other ions. Particularly noteworthy is the remarkable difference
in extraction of Hg2+ with ligand 3a containing intramolecular
H-bonds and its N-substituted analogues 1a–1c. For example,
ligand 1a showed extractability of 95.4% for Hg2+, while 3a gave
a lower value of 38.4%. The large difference (57.0%) for 1a as
compared to 3a is also revealed in 1b and 1c, which enhanced
the extraction by 50.2% and 54.6%, respectively. Compound 2,
also ethylated on amide nitrogens, behaved in a similar fashion
and showed a relatively large difference of 38.6% in extracting
Hg2+ compared to 3a. In principle, effective coordination of the
ligand with metal ions requires the orientation of two carbonyl
oxygen atoms and nitrogen of the pyridine moiety to be arrayed
on the same side.9d,39 For 3a, orientation of carbonyl oxygens
inwards in line with the pyridine nitrogen is impossible due to
rigidied backbone by intramolecular hydrogen bonds.
However, driven by the presence of metal ions transferred from
the aqueous phase in the course of extraction, rotation of
carbonyl oxygens to direct right coordination is more likely to
occur for 1a–1c even for rotamers of high energy (e.g., E–syn–
syn–Z, Z–syn–syn–Z) since the intramolecular H-bonding was
disrupted in 1a–1c aer ethylation of amide nitrogen. This
Fig. 7 Optimized rotational structures of compound 1a obtained by
DFT calculation at the B3LYP/6-31G(d) level.
conformation (1a) in the solid state is consistent to one of the
calculated results.
Liquid–liquid extraction
The structural difference between 1a and 3a is indeed man- explains the higher extractability of Hg2+ for these compounds
ifested in the following extractive results.
(88.6–95.4%) compared to 3a (38.4%). In fact, use of another
Eight transition metal picrates were employed in liquid– compound 3b containing two intramolecular hydrogen bonds
liquid extraction experiments including picrate salts of Ag+, afforded an extractability of 40.6% for Hg2+, which is very close
Hg2+, Pb2+, Cd2+, Zn2+, Cu2+, Co2+ and Ni2+. The extraction to that with 3a as extractant. This indicates that intramolecu-
abilities of picolinamides 1a–1c, 2, 3a and 3b towards these larly hydrogen-bonded extractants (3a and 3b) are inferior to
metal ions were examined by the standard picrate extraction those containing no hydrogen bonds, underscoring the
method.38 Compound 2 bearing no substituent on benzene importance of released constraint of rotational restriction for
rings was employed as a control for 1a–1c.
chelating metal ions upon extraction.
Results from extraction of the above transition metal ions
On the other hand, N-substituted groups can increase the
from water into dichloromethane are shown in Table 3 and basicity, nucleophilicity and soness of the coordinating amide
Fig. 8. All ligands exhibited good to excellent extraction ability groups and the lipophilicity of the extracted complex compared
for Hg2+. Almost no extraction or small extraction (<9%) was to N–H groups, which would also be one of reasons to enhance
detected for Pb2+, Cd2+, Zn2+, Co2+ and Ni2+ except for 1a for the extractability of 1a–1c and 2.40 As shown in Table 3, the
29708 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 3 The extractability of aqueous metal picrates for compounds 1a–1c, 2, 3a and 3b into dichloromethanea
Extractionb (%)
Metal
ion
Hydration energy41 DGhyd (kJ molꢁ1
)
1a
1b
1c
2
3a
3b
Hg2+
Ag+
ꢁ1760
ꢁ430
95.4 ꢄ 0.4
58.7 ꢄ 0.6
31.5 ꢄ 0.4
8.2 ꢄ 0.2
3.0 ꢄ 0.5
4.9 ꢄ 0
88.6 ꢄ 1.0
38.5 ꢄ 0
1.9 ꢄ 0.2
1.5 ꢄ 0.2
0.8 ꢄ 0.9
0.8 ꢄ 0.9
0.3 ꢄ 0.5
4.4 ꢄ 0.2
93.0 ꢄ 0.4
42.1 ꢄ 0.2
2.1 ꢄ 0.4
0.5 ꢄ 0.5
0.6 ꢄ 0.5
0.9 ꢄ 0.2
0.6 ꢄ 0.2
3.6 ꢄ 0.2
77.0 ꢄ 0.5
27.4 ꢄ 0.4
3.3 ꢄ 0.7
2.6 ꢄ 0.5
3.1 ꢄ 0.3
0.2 ꢄ 0.4
1.9 ꢄ 0.7
3.5 ꢄ 0.5
38.4 ꢄ 0.4
2.9 ꢄ 0.2
1.5 ꢄ 0.2
0.9 ꢄ 0.2
0.7 ꢄ 0
40.6 ꢄ 0.2
3.2 ꢄ 0.2
3.0 ꢄ 0.7
2.5 ꢄ 0.2
1.2 ꢄ 0.2
3.3 ꢄ 0.7
1.5 ꢄ 0.7
3.2 ꢄ 0.5
Cu2+
Ni2+
Cd2+
Co2+
Zn2+
Pb2+
ꢁ2010
ꢁ1980
ꢁ1755
ꢁ1915
ꢁ1955
ꢁ1425
1.2 ꢄ 0.2
2.2 ꢄ 0.2
1.2 ꢄ 0.2
7.2 ꢄ 0.5
7.9 ꢄ 0.5
a
b
Aqueous phase (10 mL); [Picꢁ] ¼ 2 ꢃ 10ꢁ5 M, organic phase (10 mL); [L] ¼ 2 ꢃ 10ꢁ4 M, 298 K. Average for three independent extraction
experiments.
for compound 2 having no electron-donating groups. Among
the four ligands 1a–1c and 2, 1c is not only with high extract-
ability but also much more selective towards extracting Hg2+
than other metal cations.
To comprehend the complexing behaviour of extracted
species in the extraction process, the stoichiometries of the
ligands and metal cations were measured. The dependence of
log{D/[Picꢁ]n} as a function of the concentration of ligands 1a–
1c at constant Hg-picrate concentration offers a linear rela-
tionship between log{D/[Picꢁ]n} and log[L] with the slopes of
2.26, 1.96 and 2.15 for 1a, 1b and 1c, respectively (Fig. 9). This
implicates the presence of the extracted species in approxi-
mately 2 : 1 (L : M) between 1a–1c and Hg2+. The values of the
extraction constants log Kex were calculated to be 17.07, 15.47
and 16.62 for 1a, 1b and 1c, respectively.
Furthermore, the method of Job's plot was used to supply
more information on the Hg2+ binding stoichiometry of 1a–1c.
Fig. 8 Extraction of transition metal picrates by compounds 1a–1c, 2,
The resulting Job's plot of 1a/1b/1c–Hg2+ complexation is shown
3a and 3b from water into dichloromethane at 298 K. Aqueous phase
(10 mL); [Picꢁ] ¼ 2 ꢃ 10ꢁ5 M, organic phase (10 mL); [L] ¼ 2 ꢃ 10ꢁ4 M.
in Fig. 10. The maximum absorbance is observed at 0.67, indi-
cating a ligand–metal ratio of 2 : 1 in the complex. On the basis
of 2 : 1 stoichiometry and UV-vis titration data (see ESI,
Fig. S29–31†), the binding constants K1 and K2 of 1a–Hg2+ in
CH3CN are estimated to be 3.34 ꢃ 107 Mꢁ1 and 1.38 ꢃ 106 Mꢁ1
extraction percentage decreased in the order of Hg2+ > Ag+
>
Cu2+ > (or ꢂ) Ni2+ ꢂ Co2+ ꢂ Zn2+ ꢂ Pb2+ ꢂ Cd2+, which does not
follow the order of hydration energy41 or ionic radii of the metal
ions41 (Pb2+ > Ag+ > Hg2+ > Cd2+ > Zn2+ ꢂ Co2+ > Cu2+ > Ni2+),
suggesting that the higher selectivity towards Hg2+could be
attributed to the synergy of several factors such as hydration of
metal ions, ionic radius, charge number and hardness/so-
ness42 between the nitrogen-containing ligands and Hg2+. The
effect of structural difference as in 1a–1c, 2, 3a and 3b upon
extraction behaviour was also unraveled by the results from
extraction of Ag+. Ligand 1a, 1b, 1c, and 2 extracted Ag+ in
58.7%, 38.5%, 42.1% and 27.4%, respectively; however, the
extractability for 3a and 3b is very low (<4%), again demon-
strating the dependence of extraction upon the presence of
intramolecular hydrogen bonds.
Regarding the extraction difference among 1a, 1b and 1c and
2, electronic effect seems to play a major role, which arises from
different substitution position of propoxy groups on benzene
rings. Ortho- and para-substitution provided highest extraction
Fig. 9 Plot of log{D/[Picꢁ]n} versus log[L] for the extraction of Hg-
results (95.4% and 93.0%). The efficiency decreased by ca. 17% picrate with ligands 1a–1c.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29709

View Article Online
RSC Advances
Paper
Fig. 12 Infrared spectra of 1a and the complex 1a–Hg2+
.
Fig. 10 Job's plot for the determination of stoichiometry in the
complex formed by 1a–1c and Hg2+ from absorbance measurements
in CH3CN.
addition of Hg2+. In sharp contrast, for compounds 3a and 3b,
neither chemical shis nor signal patterns undergo any change,
strongly suggesting that the interaction of 1a–1c with Hg2+ is
much stronger than that of 3a or 3b. This explains the much
higher efficiency as indicated for 1a–1c as extractants compared
to 3a and 3b. In general, the NMR patterns of 1a–1c tend to
become simple aer addition of Hg2+. In the case of 1a, upon
complexing the metal ion, though still poorly-resolved, the
signal pattern (Fig. 13b) resembles that from variable-temper-
ature 1H NMR experiments (Fig. 5 at 318 K). For 1b, the
broadened signals change to one set of well-resolved sharp
signals in the presence of Hg2+ (Fig. 13c and d), suggesting the
transformation from mixed multiple rotational isomers to only
one major isomer induced by introduction of metal ion. The
similar result was obtained for 1c, where minor signals of very
low intensity and major signals merge into one set of broad
signals at aromatic region (Fig. 13e and f, 6.5–7.6 ppm), while
aliphatic protons (0.8–4.2 ppm) become more distinguishable.
These results suggest that complexation of Hg2+ by 1a–1c
facilitate the reduction of possible rotational isomers in solu-
tion, but have no inuence upon isomerism for
(Fig. 11) using nonlinear curve tting method.43 Similarly, the
binding constants of 1b–Hg2+ and 1c–Hg2+ are also estimated
using the same method (see ESI, Fig. S32 and 33†).
To understand the coordinate sites of the ligands, the
complex 1a–Hg2+ was prepared from a CH3CN solution con-
taining 1a and Hg(NO3)2 in molar ratio 2 : 1 and its infrared
spectrum was compared to that of the free ligand 1a (Fig. 12).
The strong band at 1649 cmꢁ1 of n(C]O) in 1a shis to 1632
cmꢁ1 in the complex, a change of 17 cmꢁ1 from vibration of
carbonyl oxygen, indicative of the involvement of oxygen atoms
in coordination. Since the n(OC–N) band at 1264 cmꢁ1 for amide
bonds in 1a only shis upward by 2 cmꢁ1 upon complexation, it
suggests that the two amide nitrogens are not involved in the
coordination with metal ions. Besides, the band of pyridine ring
vibrations appears at 1475 cmꢁ1 in free 1a and merges into a
band at 1456 cmꢁ1 in coordinated 1a. Based on these observa-
tions, we conclude that the coordinate atoms of 1a should come
from carbonyl oxygens, and pyridine nitrogen is also involved.
The complexation of 1a–1c, 3a and 3b with Hg2+ were evi-
denced by the spectral change in the 1H NMR experiments
(Fig. 13 and 14). In CD3CN/CDCl3 (1/9, v/v), almost all of the
protons experience a downeld shi for compound 1a–1c upon
Fig. 13 Partial 1H NMR spectra in 10% CD3CN/90% CDCl3 (400 MHz,
Fig. 11 Curve-fitting analysis for the complexation of 1a with Hg2+ in 298 K): (a) 1a; (b) 1a + Hg(NO3)2 (2 : 1); (c) 1b; (d) 1b + Hg(NO3)2 (2 : 1);
CH3CN.
(e) 1c; (f) 1c + Hg(NO3)2 (2 : 1). Sign “*” represents signals of solvents.
29710 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
and provided the product as light yellow oil, which was used for
the immediate coupling reaction.
Synthesis of pyridine-based 2,6-dicarboxyamides 1a–1c, 3a
and 3b
The general procedure for compounds 1a–1c, 3a and 3b was
exemplied by the synthesis of 1a. Triethylamine (3.35 g, 33.12
mmol) was added into a solution of the amine 6a (3.32 g, 22.0
mmol) in 100 mL of dry dichloromethane at 0 ꢀC under N2.
Pyridine-2,6-dicarbonyl dichloride 4 (2.24 g, 11.0 mmol) was
dissolved in 50 mL of dichloromethane and added dropwise to
the above mixture. The solution was stirred at room tempera-
ture under N2 for 4 h. The organic layer was washed with 10%
HCl aqueous and followed water, and dried over anhydrous
Na2SO4 and ltered. Most volatiles were removed under reduced
pressure and the residue was isolated by precipitation by
addition of methanol to give a white solid.
Fig. 14 Partial 1H NMR spectra in 10% CD3CN/90% CDCl3 (400 MHz,
298 K): (a) 3a; (b) 3a + Hg(NO3)2 (2 : 1); (c) 3b; (d) 3b + Hg(NO3)2 (2 : 1).
Sign “*” represents signals of solvents.
intramolecularly hydrogen-bonded compounds 3a and 3b,
again underscoring the importance of hydrogen bonding and
rotational isomerism on extraction.
1
1a. Yield 82%. H NMR (400 MHz, CDCl3) d: 7.35–6.68 (m,
11H, ArH), 4.10–3.95 (m, 2H, NCH2), 3.88–3.70 (m, 4H, OCH2),
3.66–3.54 (m, 2H, NCH2), 1.83–1.68 (m, 4H, CH2), 1.16–1.12 (m,
6H, CH3), 1.04–0.96 (m, 6H, CH3). 13C NMR (100 MHz, CDCl3) d:
168.14, 167.78, 154.26, 154.22, 153.25, 152.67, 135.42, 135.28,
131.24, 131.09, 130.95, 130.41, 128.49, 128.44, 122.84, 122.37,
120.06, 119.98, 112.01, 111.76, 69.57, 69.50, 43.88, 43.58, 22.59,
12.58, 12.50, 10.71, 10.65. ESI-HRMS (m/z) calcd for C29H35N3O4
[M + H]+ 490.2706, [M + Na]+ 512.2525, [M + K]+ 528.2265; found
[M + H]+ 490.2701, [M + Na]+ 512.2532, [M + K]+ 528.2272.
1b. Yield 92%. 1H NMR (400 MHz, CD3COCD3) d: 7.62 (br s,
1H, PyH), 7.32 (br s, 2H, PyH), 7.10 (s, 2H, ArH), 6.78 (s, 2H,
ArH), 6.76 (d, J ¼ 8.4 Hz, 2H, ArH), 6.41 (br s, 2H, ArH), 3.90 (t, J
¼ 6.4 Hz, 4H, OCH2), 3.85 (br s, 4H, NCH2), 1.74 (m, J ¼ 6.8 Hz,
4H, CH2), 1.13 (br s, 6H, NCH2CH3), 1.00 (t, J ¼ 7.4 Hz, 6H, CH3)
13C NMR (100 MHz, CDCl3) d: 167.25, 159.56, 153.11, 143.57,
136.12, 129.36, 123.53, 120.50, 114.00, 112.94, 69.60, 45.02,
22.50, 12.80, 10.50. ESI-HRMS (m/z) calcd for C29H35N3O4 [M +
H]+ 490.2706, [M + Na]+ 512.2525, [M + K]+ 528.2265; found [M +
H]+ 490.2699, [M + Na]+ 512.2533, [M + K]+ 528.2267.
Experimental
Materials and reagents
Compounds 4 and 5a–5c were synthesized following the similar
reported procedures.44,45 Compound 7 was prepared from
hydrogenation of 5a in almost quantitative yield (see ESI†).
Dichloromethane,
picric
acid,
anhydrous
Na2SO4,
Hg(NO3)2$H2O, AgNO3, Cu(NO3)2$3H2O, Ni(NO3)2$6H2O,
Cd(NO3)2$4H2O, Zn(NO3)2$6H2O, Co(NO3)2$6H2O, Pb(NO3)2
were the analytical grade reagents and were purchased from
Chengdu Kelong Chemical Factory. All other solvents and
chemicals used for the synthesis were of reagent grade and used
as received.
Instruments and apparatus
UV-vis spectra were measured by SHIMADZU UV-2350. 1H NMR
and 13C spectra were recorded on Bruker AVANCE AV II-400
MHz (1H: 400 MHz; 13C: 100 MHz). Chemical shis are reported
in d values in ppm and coupling constants (J) are denoted in Hz.
Multiplicities are denoted as follows: s ¼ singlet, d ¼ doublet, t
¼ triplet, and m ¼ multiplet. High resolution mass data were
collected by WATERS Q-TOF Premier. CDCl3, DMSO-d6 and
CD3CN were from Cambridge Isotope Laboratories (CIL).
1
1c. Yield 88%. H NMR (400 MHz, CDCl3) d: 7.32 (t, J ¼ 8.0
Hz, 1H, PyH), 7.06 (d, J ¼ 8.0 Hz, 2H, PyH), 6.79 (d, J ¼ 8.8 Hz,
4H, ArH), 6.69 (d, J ¼ 8.4 Hz, 4H, ArH), 3.87 (q, J ¼ 7.2 Hz, 4H,
NCH2), 3.83 (t, J ¼ 6.4 Hz, 4H, OCH2), 1.76 (m, J ¼ 6.8 Hz, 4H,
CH2), 1.17 (t, J ¼ 7.0 Hz, 6H, NCH2CH3), 1.00 (t, J ¼ 7.4 Hz, 6H,
CH3). 13C NMR (100 MHz, CDCl3) d: 167.35, 157.61, 153.46,
135.67, 134.74, 129.18, 122.99, 114.30, 69.43, 44.77, 22.38,
12.47, 10.35. ESI-HRMS (m/z) calcd for C29H35N3O4 [M + H]+
490.2706, [M + Na]+ 512.2525, [M + K]+ 528.2265; found [M + H]+
Synthesis of compound 6a–6c
Compound 6a–6c was synthesized following the reported 490.2699, [M + Na]+ 512.2528, [M + K]+ 528.2269.
procedure in a yield of 79%, 81%, 73%, respectively.27 Aer two 3a. Yield 81%. 1H NMR (400 MHz, CDCl3) d: 10.20 (s, 2H,
vacuum/H2 cycles to remove air from the reaction, the stirred NH), 8.45 (d, J ¼ 7.6 Hz, 2H, ArH), 8.40 (d, J ¼ 8 Hz, 2H, PyH),
mixture of the nitropropoxybenzene 5a/5b/5c (1.00 g, 5.52 8.09–8.05 (t, J ¼ 8 Hz, 1H, PyH), 7.06–7.03 (t, J ¼ 7.2 Hz, 2H,
mmol), 100 mg 10% Pd/C and 50 mL acetonitrile was hydro- ArH), 7.00–6.96 (t, J ¼ 7.6 Hz, 2H, ArH), 6.85 (d, J ¼ 8 Hz, 2H,
genated at ordinary pressure and at room temperature. The ArH), 3.90–3.87 (t, J ¼ 6.4 Hz, 4H, OCH2), 1.63–1.54 (m, 4H,
reaction was monitored using TLC until the secondary amine CH2), 0.75–0.71 (t, J ¼ 7.6 Hz, 6H, CH3). 13C NMR (100 MHz,
was no longer increased. The reaction mixture was ltrated and CDCl3) d: 160.15, 148.56, 147.25, 138.43, 126.07, 124.05, 123.48,
the ltrate was concentrated under reduced pressure. The crude 119.94, 119.14, 109.97, 69.03, 21.20, 9.12. ESI-HRMS (m/z) calcd
mixture was puried by ash silica gel column chromatography, for C25H27N3O4 [M + H]+ 434.2080, [M + Na]+ 456.1899, [M + K]+
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29711

View Article Online
RSC Advances
Paper
472.1639; found [M + H]+ 434.2082, [M + Na]+ 456.1894, [M + K]+ (a, b and c), compound 2 still displayed a lower extraction ability
472.1647. than 1 (a, b and c) due to the favorable electronic effect arising
3b. Yield 89%. 1H NMR (400 MHz, CDCl3) d: 9.45 (s, 2H, NH), from alkoxy substitution. The stoichiometry for the complexa-
8.55 (d, J ¼ 7.6 Hz, 2H, PyH), 8.20–8.16 (t, J ¼ 7.6 Hz, 1H, PyH), tion of Hg2+ by 1a–1c was found to be 2 : 1 (ligand/metal ion)
8.16 (d, J ¼ 8.0 Hz, 2H, ArH), 7.34–7.30 (t, J ¼ 7.6 Hz, 2H, ArH), using log{D/[Picꢁ]n} ꢁ log[L] analysis, Job's plot and UV-vis
7.27 (d, J ¼ 7.6 Hz, 2H, ArH), 7.18–7.14 (t, J ¼ 7.6 Hz, 2H, ArH), titration. IR study indicates that the coordinate atoms are
2.44 (s, 6H, CH3). 13C NMR (100 MHz, CDCl3) d: 160.20, 148.14, carbonyl oxygens and pyridine nitrogen in N-substituted
138.56, 129.58, 127.82, 126.00, 124.53, 121.68, 16.96. ESI-HRMS ligands. The disclosure of the impact of H-bonding-enforced
(m/z) calcd for C21H19N3O2 [M + H]+ 346.1556, [M + Na]+ backbone rigidication and structural variation via N-substitu-
368.1375, [M + K]+ 384.1114; found [M + H]+ 346.1554, [M + Na]+ tion upon extraction as presented in this work may provide in-
368.1375, [M + K]+ 384.1110.
depth understanding of the extraction process associated with
intramolecular hydrogen bonding and rotational conformation.
Solvent extraction
Acknowledgements
Heavy metal picrates were prepared by the stepwise addition of
1 ꢃ 10ꢁ2 M of metal nitrate solution to 2 ꢃ 10ꢁ5 M aqueous
picric acid solution and shaken at 298 K for 1 h. 10 mL of a 2 ꢃ
10ꢁ5 M aqueous metal picrate solution and 10 mL of a 2 ꢃ 10ꢁ4
M solution of ligands in CH2Cl2 were placed in a stoppered glass
tube and vigorously agitated with a mechanical shaker in a
thermostated water bath at 298 K for 2 h. The resulting mixtures
were le standing for an additional 2 h in order to complete the
phase separation. The concentration of the picrate anion
remaining in the aqueous phase was determined by UV spec-
trophotometry at lmax 355 nm. Blank experiments showed that
no picrate extraction occurred in the absence of ligands. The
extractability was determined based on the absorbance of pic-
rate anion in the aqueous solutions. The extractability (E%) was
calculated based on the equation: E% ¼ 100(A0 ꢁ A)/A0, where A0
is the absorbance of the aqueous solution in the absence of
ligand, A is the absorbance of the aqueous phase aer extrac-
tion. Three independent experiments were carried out and the
average value of percent picrate extracted was calculated.
This work is supported by the National Natural Science Foun-
dation (21172158), NSAF(11076018), the Doctoral Program of
the Ministry of Education of China (20130181110023), the
National Science Foundation for Fostering Talents in Basic
Research of the National Natural Science Foundation of China
(J1210004 and J1103315), Open Project of State Key Laboratory
of Supramolecular Structure and Materials (SKLSSM201408)
and Open Project of State Key Laboratory of Structural Chem-
istry (20140013). Comprehensive Training Platform of Special-
ized Laboratory, College of Chemistry, Sichuan University is
acknowledged for NMR, HRESI-MS and IR analyses.
Notes and references
1 D. W. Zhang, X. Zhao, J. L. Hou and Z. T. Li, Chem. Rev., 2012,
112, 5271.
2 (a) A. E. V. Gorden, M. A. DeVore, II and B. A. Maynard, Inorg.
Chem., 2013, 52, 3445; (b) B. J. Mincher, G. Modolo and
S. P. Mezyk, Solvent Extr. Ion Exch., 2009, 27, 579.
3 (a) H. N. Kim, M. H. Lee, H. J. Kim, J. S. Kim and J. Yoon,
Chem. Soc. Rev., 2008, 37, 1465; (b) I. G. Spiridonov,
D. O. Kirsanov, V. A. Babain, M. Y. Alyapyshev,
N. I. Eliseev, Y. G. Vlasov and A. V. Legin, Russ. J. Appl.
Conclusion
In summary, a pyridine-based aromatic amides 1a–1c with
N-substitution and their analogues 3a and 3b containing
intramolecular hydrogen bonds were synthesized for probing
the interplay of molecular structure and liquid–liquid extrac-
tion behaviour towards transition metal ions. X-ray diffraction
analysis of ligands 1a and 3a provides information of molecular
conformation without and with intramolecular H-bonding. The
observed E–anti–anti–E conformation (1a) in the solid sate is
among one of six reasonable rotational isomeric structures of 1a
optimized by computer modeling. Ordinary and variable-
temperature proton and carbon NMR experiments of 1a–1c
disclosed the formation of rotamers due to N-substitution. The
fact that N-substitution is responsible for the higher selectivity
and efficiency towards Hg2+ over other metal cations is ratio-
nalized by the large difference in rotational restriction between
N-substituted 1 (a, b and c) and intramolecularly hydrogen
bonded 3 (a, b). The results from 1H NMR spectra regarding the
interaction of the ligands with Hg2+ also verify the extraction
difference, and simultaneously disclose the inuence of
complexation on rotational isomerism of ligands. Despite the
absence of intramolecular hydrogen bonding as compounds 1
¨
Chem., 2011, 84, 1354; (c) U. Ocak, M. Ocak, X. Shen,
K. Surowiec and R. A. Bartsch, J. Fluoresc., 2009, 19, 997;
¨
(d) U. Ocak, M. Ocak, K. Surowiec, X. Liu and R. A. Bartsch,
¨
Tetrahedron, 2009, 65, 7038; (e) M. A. Qazi, U. Ocak,
M. Ocak, S. Memon and I. B. Solangi, J. Fluoresc., 2013, 23,
575.
4 (a) P. Geoghegan and P. O'Leary, ACS Catal., 2012, 2, 573; (b)
N. Kumagai and M. Shibasaki, Angew. Chem., Int. Ed., 2013,
52, 223.
5 S. A. Ansari, P. Pathak, P. K. Mohapatra and
V. K. Manchanda, Chem. Rev., 2012, 112, 1751.
6 (a) A. Casnati, N. Della Ca', M. Fontanella, F. Sansone,
F. Ugozzoli, R. Ungaro, K. Liger and J. F. Dozol, Eur. J. Org.
Chem., 2005, 2338; (b) E. Macerata, F. Sansone, L. Baldini,
F. Ugozzoli, F. Brisach, J. Haddaoui, V. Hubscher-Bruder,
F. Arnaud-Neu, M. Mariani, R. Ungaro and A. Casnati, Eur.
J. Org. Chem., 2010, 2675; (c) M. Galletta, L. Baldini,
F. Sansone, F. Ugozzoli, R. Ungaro, A. Casnati and
M. Mariani, Dalton Trans., 2010, 39, 2546.
29712 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
´
´
7 (a) M. M. Reinoso-Garcıa, D. Janczewski, D. N. Reinhoudt, 17 X. Yang, L. Chen, Y. Yang, Y. He, S. Zou, W. Feng, Y. Yang,
´ˇ
W. Verboom, E. Malinowska, M. Pietrzak, C. Hill, J. Baca,
N. Liu, J. Liao and L. Yuan, J. Hazard. Mater., 2012, 217–
218, 171.
¨
¨
B. Gruner, P. Selucky and C. Gruttner, New J. Chem., 2006,
30, 1480; (b) K. Matloka, A. K. Sah, M. W. Peters, 18 (a) L. Yang, L. Zhong, K. Yamato, X. Zhang, W. Feng, P. Deng,
P. Srinivasan, A. V. Gelis, M. Regalbuto and M. J. Scott,
Inorg. Chem., 2007, 46, 10549; (c) E. V. Sharova,
O. I. Artyushin, A. N. Turanov, V. K. Karandashev,
S. B. Meshkova, Z. M. Topilova and I. L. Odinets, Cent. Eur.
J. Chem., 2012, 10, 146.
8 (a) A. Shimada, T. Yaita, H. Narita, S. Tachimori and
K. Okuno, Solvent Extr. Ion Exch., 2004, 22, 147; (b)
M. Y. Alyapyshev, V. A. Babain, N. E. Borisova,
R. N. Kiseleva, D. V. Safronov and M. D. Reshetova,
L. Yuan, X. C. Zeng and B. Gong, New J. Chem., 2009, 33, 729;
(b) W. Feng, K. Yamato, L. Yang, J. S. Ferguson, L. Zhong,
S. Zou, L. Yuan, X. C. Zeng and B. Gong, J. Am. Chem. Soc.,
2009, 131, 2629; (c) Y. Yang, W. Feng, J. Hu, S. Zou, R. Gao,
K. Yamato, M. Kline, Z. Cai, Y. Gao, Y. Wang, L. Li,
Y. Ynag, L. Yuan, X. C. Zeng and B. Gong, J. Am. Chem.
Soc., 2011, 133, 18590; (d) J. Hu, L. Chen, Y. Ren, P. Deng,
X. Li, Y. Wang, Y. Jia, J. Luo, X. Yang, W. Feng and
L. Yuan, Org. Lett., 2013, 15, 4670.
Mendeleev Commun., 2008, 18, 336; (c) A. Paulenova, 19 L. Zhong, L. Chen, W. Feng, S. Zou, Y. Yang, N. Liu and
M. Y. Alyapyshev, V. A. Babain, R. S. Herbst and J. D. Law,
L. Yuan, J. Inclusion Phenom. Macrocyclic Chem., 2012, 72,
Sep. Sci. Technol., 2008, 43, 2606; (d) M. Y. Alyapyshev,
367.
V. A. Babain, L. I. Tkachenko, A. Paulenova, A. A. Popova 20 L. He, Q. Jiang, Y. Jia, Y. Fang, S. Zou, Y. Yang, J. Liao, N. Liu,
and N. E. Borisova, Solvent Extr. Ion Exch., 2014, 32, 138.
9 (a) J. C. Noveron, M. M. Olmstead and P. K. Mascharak, J. Am.
W. Feng, S. Luo, Y. Yang, L. Yang and L. Yuan, J. Chem.
Technol. Biotechnol., 2013, 88, 1930.
Chem. Soc., 2001, 123, 3247; (b) T. C. Harrop, L. A. Tyler, 21 H. Chu, L. He, Q. Jiang, Y. Fang, Y. Jia, X. Yuan, S. Zou, X. Li,
M. M. Olmstead and P. K. Mascharak, Eur. J. Inorg. Chem.,
2003, 475; (c) R. Kapoor, A. Kataria, A. Pathak,
W. Feng, Y. Yang, N. Liu, S. Luo, Y. Yang, L. Yang and
L. Yuan, J. Hazard. Mater., 2014, 264, 211.
P. Venugopalan, G. Hundal and P. Kapoor, Polyhedron, 22 (a) J. L Lapka, A. Paulenova, M. Y. Alyapyshev, V. A. Babain,
2005, 24, 1221; (d) R. Kapoor, A. Kataria, P. Kapoor and
P. Venugopalan, Transition Met. Chem., 2004, 29, 425; (e)
R. Kapoor, A. Kataria, P. Venugopalan and P. Kapoor,
Inorg. Chem., 2004, 43, 6699.
J. D. Law and R. S. Herbst, IOP Conf. Ser.: Mater. Sci. Eng.,
2010, 9, 012068; (b) J. L. Lapka, A. Paulenova, R. S. Herbst
and J. D. Law, Sep. Sci. Technol., 2010, 45, 1706; (c)
M. Y. Alyapyshev, V. A. Babain, L. I. Tkachenko,
I. I. Eliseev, A. V. Didenko and M. L. Petrov, Solvent Extr.
Ion Exch., 2011, 29, 619; (d) A. Paulenova, M. Y. Alyapyshev,
V. A. Babain, R. S. Herbst and J. D. Law, Solvent Extr. Ion
Exch., 2013, 31, 184.
10 (a) D. O. Kirsanov, N. E. Borisova, M. D. Reshetova,
A. V. Ivanov, L. A. Korotkov, I. I. Eliseev, M. Y. Alyapyshev,
I. G. Spiridonov, A. V. Legin, Y. G. Vlasov and
V. A. Babain, Russ. Chem. Bull., Int. Ed., 2012, 61, 881; (b)
J. L. Lapka, A. Paulenova, M. Y. Alyapyshev, V. A. Babain, 23 (a) M. Alyapyshev, V. Babain, N. Borisova, I. Eliseev,
R. S. Herbst and J. D. Law, J. Radioanal. Nucl. Chem.,
2009, 280, 307.
D. Kirsanov, A. Kostin, A. Legin, M. Reshetova and
Z. Smirnova, Polyhedron, 2010, 29, 1998; (b) T. L. Borgne,
´
11 (a) A. Fujiwara, Y. Nakano, T. Yaita and K. Okuno, J. Alloys
Compd., 2008, 456, 429; (b) J. L. Lapka, A. Paulenova,
J. M. Benech, S. Floguet, G. Bernardinelli, C. Aliprandini,
P. Bettens and C. Piguet, Dalton Trans., 2003, 3856.
L. N. Zakharov, M. Y. Alyapyshev and V. A. Babain, IOP 24 L. Wu, Y. Fang, Y. Jia, Y. Yang, J. Liao, N. Liu, X. Yang,
Conf. Ser.: Mater. Sci. Eng., 2010, 9, 012029. W. Feng, J. Ming and L. Yuan, Dalton Trans., 2014, 43, 3835.
12 V. A. Babain, M. Y. Alyapyshev, I. V. Smirnov and 25 (a) V. A. Babain, M. Y. Alyapyshev and R. N. Kiseleva,
ˇ
Radiochim. Acta, 2007, 95, 217; (b) E. Makrlik, P. Vanura,
A. Y. Shadrin, Radiochemistry, 2006, 48, 369.
¨
´
13 (a) H. Stephan, K. Gloe, J. Beger and P. Muhl, Solvent Extr. Ion
P. Selucky, V. A. Babain and M. Y. Alyapyshev,
Exch., 1991, 9, 435; (b) Y. Sasaki and G. R. Choppin, Anal. Sci.,
1996, 12, 225.
14 M. Y. Alyapyshev, V. A. Babain, L. I. Tkachenko, I. I. Eliseev,
A. V. Didenko and M. L. Petrov, Solvent Extr. Ion Exch., 2011,
29, 619.
15 (a) S. L. Li, T. Xiao, C. Lin and L. Wang, Chem. Soc. Rev., 2012,
41, 5950; (b) L. Yuan, P. Zhang, W. Feng and B. Gong, Curr.
Org. Chem., 2011, 15, 1250; (c) P. K. Baruah and S. Khan, RSC
Adv., 2013, 3, 21202; (d) P. A. Gale, N. Busschaert,
C. J. E. Haynes, L. E. Karagiannidis and I. L. Kirby, Chem.
Soc. Rev., 2014, 43, 205.
Radiochemistry, 2009, 51, 479; (c) D. O. Kirsanov,
O. V. Mednova, E. N. Pol'shin, A. V. Legin,
M. Y. Alyapyshev, I. I. Eliseev, V. A. Babain and
Y. G. Vlasov, Russ. J. Appl. Chem., 2009, 82, 247; (d)
´
ˇ
´
E. Makrlık, P. Vanura, P. Selucky, V. A. Babain and
I. V. Smirnov, J. Radioanal. Nucl. Chem., 2010, 283, 839; (e)
M. Y. Alyapyshev, V. A. Babain, L. I. Tkachenko,
I. I. Eliseev, A. V. Didenko and M. L. Petrov, Solvent Extr.
Ion Exch., 2011, 29, 619; (f) D. Kirsanov, A. Legin,
M. Tkachenko, I. Surzhina, M. Khaidukova and V. Babain,
AIP Conf. Proc., 2011, 1362, 104.
16 (a) Z. Shirin, J. Thompson, L. Liable-Sands, G. P. A. Yap, 26 M. Y. Alyapyshev, V. A. Babain, Y. A. Pokhitonov and
A. L. Rheingold and A. S. Borovik, J. Chem. Soc., Dalton V. M. Esimantovskiy, Adv. Nucl. Fuel Cycles Syst., 2007, 1836.
Trans., 2002, 1714; (b) J. R. Turkington, P. J. Bailey, 27 H. Sajiki, T. Ikawa and K. Hirota, Org. Lett., 2004, 6, 4977.
J. B. Love, A. M. Wilson and P. A. Tasker, Chem. Commun., 28 (a) T. J. Bartczak, Z. M. Michlska, B. Ostaszewski, P. Sobota
2013, 49, 1891.
and K. Strzelec, Inorg. Chim. Acta, 2001, 319, 229; (b)
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 29702–29714 | 29713

View Article Online
RSC Advances
Paper
D. S. Marlin, M. M. Olmstead and P. K. Mascharak, J. Mol.
Struct., 2000, 554, 211; (c) A. Itai, Y. Toriumi, S. Saito,
H. Kagechika and K. Shudo, J. Am. Chem. Soc., 1992, 114,
10649.
J. A. Montgomery, Jr, R. E. Stratmann, J. C. Burant,
S. Dapprich, J. M. Millam, A. D. Daniels, K. N. Kudin,
M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi,
R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford,
J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui,
K. Morokuma, N. Rega, P. Salvador, J. J. Dannenberg,
D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. Gomperts, R. Martin, L. D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen,
M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon,
E. S. Replogle and J. A. Pople, Gaussian Inc., Wallingford,
CT, 2004.
29 (a) Q. Y. Yang, Z. Y. Zhou and J. Y. Qi, Acta Crystallogr., 2001,
E57, o1161; (b) M. F. Mayer, S. Nakashima and
S. C. Zimmerman, Org. Lett., 2005, 7, 3005; (c) X. Li, Y. Jia,
Y. Ren, Y. Wang, J. Hu, T. Ma, W. Feng and L. Yuan, Org.
Biomol. Chem., 2013, 11, 6975.
´
30 (a) B. Dolensk´y, R. Konvalinka, M. Jakubek and V. Kral,
´
J. Mol. Struct., 2013, 1035, 124; (b) J. G. Sosnicki and
P. E. Hansen, J. Mol. Struct., 2004, 700, 91.
31 Y. Hamuro, S. J. Geib and A. D. Hamilton, J. Am. Chem. Soc.,
1996, 118, 7529.
32 (a) W. E. Stewart and T. H. Siddall III, Chem. Rev., 1970, 70,
517; (b) N. Ototake, T. Taguchi and O. Kitagawa, Tetrahedron 38 (a) M. Ocak, H. Alp, H. Kantekin, H. Karadeniz and
¨
Lett., 2008, 49, 5458; (c) J. S. Laursen, J. Engel-Andreasen,
P. Fristrup, P. Harris and C. A. Olsen, J. Am. Chem. Soc.,
2013, 135, 2835.
U. Ocak, J. Inclusion Phenom. Macrocyclic Chem., 2008, 60,
¨
¨
17; (b) H. Alp, M. Ocak, M. Ozdemir and U. Ocak, Sep.
¨
¨
Sci. Technol., 2006, 41, 3039; (c) U. Ocak, H. Alp, P. Gokçe
33 (a) B. Gong, Acc. Chem. Res., 2008, 41, 1376; (b) L. Yuan,
W. Feng, K. Yamato, A. R. Sanford, D. Xu, H. Guo and
B. Gong, J. Am. Chem. Soc., 2004, 126, 11120.
and M. Ocak, Sep. Sci. Technol., 2006, 41, 391; (d)
¨
¨
¨
U. Ocak, Y. Gok and H. B. ¸Senturk, Sep. Sci. Technol.,
2009, 44, 1240.
34 J. F. Malone, C. M. Murray, G. M. Dolan, R. Docherty and 39 P. Kapoor, A. Kumar, J. Nistandra and P. Venugopalan,
A. J. Lavery, Chem. Mater., 1997, 9, 2983. Transition Met. Chem., 2000, 25, 465.
´ˇ
´
´
ˇ ˇ
35 B. Klepetarova, E. Makrlık, V. A. Babain and V. Kasicka, Acta 40 M. Iqbal, P. K. Mohapatra, S. A. Ansari, J. Huskens and
Crystallogr., 2012, E68, o1099. W. Verboom, Tetrahedron, 2012, 68, 7840.
36 (a) N. H. Shah, G. L. Butterfoss, K. Nguyen, B. Yoo, 41 Y. Marcus, J. Chem. Soc., Faraday Trans., 1991, 87, 2995.
¨
¨
R. Bonneau, D. L. Rabenstein and K. Kirshenbaum, J. Am. 42 (a) H. Alp, H. Z. Gok, H. Kantekin and U. Ocak, J. Hazard.
Chem. Soc., 2008, 130, 16622; (b) B. F. Pedersen and
B. Pedersen, Tetrahedron Lett., 1965, 34, 2995; (c)
Mater., 2008, 159, 519; (b) N. Singh and D. O. Jang,
J. Hazard. Mater., 2009, 168, 727.
R. Yamasaki, A. Tanatani, I. Azumaya, S. Saito, 43 P. Thordarson, Chem. Soc. Rev., 2011, 40, 1305.
K. Yamaguchi and H. Kagechika, Org. Lett., 2003, 5, 1265.
44 Y. Y. Zhu, C. Cui, N. Li, B. W. Wang, Z. M. Wang and S. Gao,
37 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
Eur. J. Org. Chem., 2013, 17, 3101.
M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, 45 J. S. Bae and H. S. Freeman, Fibers Polym., 2002, 3, 140.
29714 | RSC Adv., 2014, 4, 29702–29714
This journal is © The Royal Society of Chemistry 2014