Design and synthesis of Tr?ger's base ditopic receptors: host-guest interactions, a combined theoretical and experimental study

Article abstract of DOI:10.1039/c4ob02266a

Two flexible Tr?ger's base ditopic receptors C4TB and C5TB incorporating monoaza crown ether were designed and synthesized for bisammonium ion complexation. A comprehensive study of host-guest interactions was established by ¹H NMR spectroscopy

Full text of DOI:10.1039/c4ob02266a

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ARTICLE TYPE
Design and Synthesis of Tröger’s Base Ditopic Receptors: Host-Guest
Interactions, a Combined Theoretical and Experimental Study
Manda Bhaskar Reddy,a Myadaraboina Shailaja,a Alla Manjula,*aJoseph Richard Premkumar,b
Garikapati Narahari Sastry,*b Katukuri Sirisha,c and Akkela Venkata Subramanya Sarmac
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Two flexible Tröger’s base ditopic receptors C4TB and C5TB incorporating monoaza crown ether were
designed and synthesized for bisammonium ion complexation. Comprehensive study of hostꢀguest
1
interactions were established by H NMR spectroscopy and DFT calculations. Bisammonium chloride
10 (A1) with shorter alkyl chain spacer showed highest affinity for the receptors. M06ꢀ2X/ccꢀpVTZ
calculations including the solvent effects on hostꢀguest complexes were employed to explain and
rationalize the experimental trends. The short NꢀH…O or NꢀH…N hydrogenꢀbond distances observed in
the range of 1.71ꢀ1.98 Å, indicate the existence of a strong charge assisted hydrogen bonding between
1
host and guest. The unusual behaviour (higher binding constant) of A5 in H NMR titration is traced to
15 the conformational folding of the guest.
two stereogenic nitrogen atoms which could be resolved into a
Introduction
chiral host.[8] The two crowns were directly built on the phenyl
rings of the Tröger’s base resulting in an excessively rigid host.
The quest for imitating the biological systems has led to the
development of supramolecular chemistry which deals not only
20 with synthesis of specific hosts for ligand binding but also
molecular recognition and self assembly of molecular
frameworks involving weak nonꢀcovalent interactions.[1] The
earliest discovered supramolecular systems, crown ethers, have
found several applications such as cation binders and phase
25 transfer catalysts.[2] Designing specific receptors with capability
of recognition of organic cations especially ammonium ions is a
topic of outstanding importance and relevance because several
bioꢀorigin amines are being used as probes to measure the quality
of food products of marine origin. Their widespread occurrence
30 in the nature and many promising applications led to the
development of effective receptors for amines. Crown ethers are
desirable chemosensors or hosts for amines because of their
ability to form strong complexes with organic cations.
Recognition of bisammonium ions by specific receptors is an
35 interesting challenge wherein selectivity depends on precise
complementarity between bisammonium ion and receptor cavity
size as well as the spacer chain length. The binding of these
bidentate guests is best done by ditopic receptors. Since crown
ethers are well known to form strong complexes with cation and
+
50 Also since NH4 is a highly directional guest (from solid state
structures),[9] addition of certain amount of flexibility would
make the host more dynamic. This leaves enough scope for
designing a ditopic cation receptor containing Tröger’s base that
is flexible and dynamic showing good complementary face to
55 face binding with ammonium ions. This can be achieved by
adding a small alkyl linker between Tröger’s base phenyl ring
and the crown ether. Thus, new ditopic cation binding receptors
C4TB and C5TB were designed (Figure 1). The current study
involves the synthesis of Tröger’s base bis(monoaza crown
60 ethers) and their hostꢀguest complexation with bisammonium
1
ions, followed by H NMR titrations and computational studies
on hostꢀguest interactions.
+
40 NH4 ions, they were chosen as ligands for the design of ditopic
receptors for bisammonium ions as is exemplified by numerous
literature examples.[3]
Among these receptors,
a
Tröger’s base[4,5,6] bidentate
receptor incorporating oxa crown ether reported by Wärnmark et
45 al[7] is of particular interest. Tröger’s base has a unique C2ꢀ
symmetric, Vꢀshaped geometry and an inherent chirality due to
Figure 1. C4TB and C5TB receptors designed in this study for
65 bisammonium ion recognition.
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NMR Titrations
Results and Discussion
Synthesis of receptors C4TB and C5TB: The synthetic strategy
for designed molecules involved a crucial precursor, 1ꢀ(2ꢀ
bromoethoxy)ꢀ4ꢀnitrobenzene 1, which was prepared by the
condensation of 4ꢀnitrophenol and 2ꢀchloroethanol followed by
bromination (PBr3) of hydroxyl group. Coupling of mono aza
crown ether C4 (synthesis of aza crowns from various ethylene
glycols is done following reported protocols)[10] to 4ꢀ
bromoethoxy nitrobenzene 1 followed by reduction of ꢀNO2
5
10 group in compound 2 to amine in compound 3 using SnCl2.2H2O
and condensation of resulting amine with paraformaldehyde in
presence of TFA yields the desired ditopic receptor as shown in
Scheme 1. But synthesis of C4TB by this approach was
frustrating owing to very low yields as well as target compound
15 could not be isolated in pure form.
Figure 2. Bisammonium chlorides Am, m = 1-6 used in the study
40 as guest molecules.
Complexation studies of various primary bisammonium ions with
two receptors were carried out using 1H NMR titration method. A
solution of host C4TB/C5TB was titrated by adding incremental
amounts of guests Am, m = 1-6 (Figure 2) until no further
45 chemical shift changes were observed in CD3OD. Low solubility
of the bisammonium ions ruled out other solvents such as CDCl3,
CD3CN and DMSOꢀd6 solvents for this study.
Scheme 1. Synthetic route to receptor C4TB.
An alternative approach starting from 4ꢀbromoethoxy
nitrobenzene 1 is shown in Scheme 2. Reduction of nitro
20 compound 1 to amine 4 was achieved using SnCl2.2H2O. 4ꢀ
Bromoethoxy amino benzene 4 was subjected to Tröger’s base
formation reaction in formalin and HCl conditions. Tröger’s base
5 was isolated in 27% yield after purification. This is the key
intermediate for the synthesis of receptors. The corresponding aza
25 crown ethers were directly coupled to the Tröger’s base 5 in
presence of K2CO3 and acetonitrile conditions. Two Tröger’s
base ditopic receptors C4TB and C5TB incorporating mono aza
crown ether (two units) were synthesized as shown in Scheme 2
and they were isolated as foams in 68% and 74% yield,
1
30 respectively. All new compounds were characterised by H, 13C
NMR spectroscopy and mass spectrometry (NMR spectra of new
compounds are provided in the Supporting Information).
50 Figure 3. Partial 1H NMR spectrum (600 MHz, CD3OD at 293 K)
of (a) free host C4TB, (b) free guest A1, (c) complex of C4TB
and A1 shows downfield shift of host –CH2ꢀNꢀCH2 signal and
upfield shift of guest signals indicates a strong complex
formation.
Scheme 2. Synthetic route to receptors C4TB and C5TB.
35
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The free host crown ether signals and DMSOꢀd6 signals merge
making impossible to distinguish the chemical shift changes. In
each case, a distinguishable proton was monitored as a function
of substrate concentration (Figure 3). Chemical shift changes that
better fit. Since the distance between the oxa crown ethers is
higher, resulting in strong complex formation with longer chain
bisammonium ion. On the other hand, C4TB is flexible with a
chain linker, thus the aza crown ethers could bind stronger with
5
were dependent on the substrate and receptor concentration ratio 45 short bisammonium ion (A1). Further the binding constants
were taken as evidence for complexation. The aromatic and
bridge protons are shifted downfield by 0.01ꢀ0.05 ppm and
complexed aza crown ether ꢀCH2ꢀNꢀCH2ꢀ protons by 0.04ꢀ0.27
ppm compared to free receptor protons (Figure 3). Interestingly,
decrease as the function of chain length increases up to A4.
Interestingly, the association constant of A5 is found to be higher
than A4. This could be attributed either due to both host
flexibility and conformational folding of the guest A5.
10 the αꢀprotons of the guest molecules moved upfield by 0.20ꢀ0.30
ppm. This indicates a strong complex formation.
50
Titrations were performed with monoammonium ion
+
CH3NH3 Clꢀ, also. However, when compared to bisammonium
ions, crown ether signals shifted to upfield (instead of downfield)
upon incremental addition of guest. This indicates that
ammonium ion was probably not bound inside the cavity of
A titration curve between ꢁδ and [G]/[H] was analyzed to
determine the stoichiometry of the complex. A break in the
15 titration curve (∆δ vs [G]/[H]) established a 1:1 stoichiometry for 55 crown ethers but it was held in between both the crowns
all the bisammonium ions with the receptor C4TB. The change in
chemical shift values of the host protons in the complex spectrum
as the function of increase in guest concentration are fitted by
using equation 1 to determine the binding constants.[11] The
20 calculated binding constants are listed in Table 1.
(sandwiched type) and methyl group stands out projecting into
the concave cavity of Tröger’s base. Upfield shifts of crown ether
protons may be due to repulsions with methyl protons of guest.
Chemical shift changes were very low which indicates weak
60 interactions between host and guest. A perfect sigmoidal curve of
ꢁδ vs [G] also indicates the 1:1 complexation (sandwich type
complex; not 1host:2guest mode of binding as expected, see
supporting information).
.. (1)
In case of complex formed between receptor C5TB and
65 bisammonium ions, due to overlapping of crown ether ꢀCH2ꢀ and
αꢀprotons of bisammonium ion signals in H NMR, the chemical
Where ∆δ = δobsꢀδh
1
Table 1. Association constants of host C4TB with bisammonium
25 ions (Am; m = 1-6).
shift changes were not distinguishable. Extremely small chemical
shift changes were observed for aromatic and bridge protons. Due
to nonꢀavailability of a clearly distinguishable proton in the host,
70 the association constants could not be evaluated. Discouraged by
the poor resolution of 1H NMR signals and lack of
distinguishable protons in C5TB-bisammonium ion complexes,
synthesis of higher aza crown ether analogue of Tröger’s base
was not attempted (even though mono azaꢀ18ꢀcrownꢀ6 has been
75 reported as best fit for ammonium ions).[13]
Bisammonium ion (Am, m = 1-6)
1,3ꢀpropane bisammonium chloride (A1) 52±0.034 0.3332±0.03736
1,4ꢀbutane bisammonium chloride (A2) 40±0.011 0.2145±0.00452
1,5ꢀpentane bisammonium chloride (A3) 27±0.012 0.1567±0.01563
1,6ꢀhexane bisammonium chloride (A4) 20±0.010 0.1481±0.01781
1,7ꢀheptane bisammonium chloride (A5) 44±0.004 0.1655±0.00344
1,8ꢀoctane bisammonium chloride (A6) 21±0.013 0.2824±0.04436
Ka (Mꢀ1)
∆δmax
Computational studies
In order to rationalize the experimental investigations,
quantum chemical calculations on complexes formed by C4TB
and C5TB with six bisammonium ions (Am; m = 1ꢀ6) have been
80 performed at PCMꢀM06ꢀ2X/ccꢀpVTZ//PCMꢀM06ꢀ2X/6ꢀ31G(d)
level of theory. The C4TB…Am and C5TB…Am complexes were
built as the bisammonium ions exist in their extended
conformation between the crowns of C4TB and C5TB. The
interaction of C4TB and C5TB with Am is mainly due to charge
85 assisted hydrogen bonding (CAHB) between O/N atom
(hydrogen bond acceptor) in the crown moiety and the NꢀH
(hydrogen bond donor) bond of the bisammonium ion. The
C4TB…Am and C5TB…Am hostꢀguest complexes exhibit two
different hydrogen bonding interactions such as NꢀH…O and Nꢀ
90 H…N. The nitrogen and oxygen ratio of the crown ethers in the
C4TB and C5TB systems are 2:6 and 2:8, respectively.
Consequently, in any set of C4TB…Am or C5TB…Am
complexes, the H…O type interactions were larger in number than
H…N type of interactions. Among several hydrogen bonds exist
95 in the hostꢀguest complexes, the shorter hydrogen bond in
C4TB…Am and C5TB…Am have been identified. The shortest
hydrogen bond distances (H…N and H…O) of C4TB…Am and
The binding constants are on the lower side probably due to
solvent effects. It has been well documented in literature that the
polarity of the solvent played an important role on complexation
and binding constants are high in low polar solvents.[12] Herein,
30 due to high polar nature and hydrogen bondꢀacceptor nature of
CD3OD used as solvent in 1H NMR titrations, low binding
constants were observed (CD3OD can easily coordinate with
+
NH4 ion and weaken the complexation with crown ether hetero
atoms). Binding constants for receptor C4TB show that Ka value
35 for the protonated bisammonium ions decreases as the function of
increase in chain length. From the summarized binding constant
values, it is clear that the guest (A1) with shorter alkyl chain
spacer was the best fit into the cavity of the receptor. Wärnmark’s
receptor9 where the oxa crown ether was directly attached to the
40 phenyl ring, showed 1,7ꢀheptane bisammonium ion A5 to be a
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C5TB…Am complexes ranges from 1.71ꢀ1.98
Å and the
Table 2. The charge transfer (CT, in a.u) between the host and
guests obtained from Mullikan charges at M06ꢀ2X/ccꢀpVTZ level
on PCMꢀM06ꢀ2X/6ꢀ31G(d) structures. The numbers inside the
45 parenthesis are CT for C4TB-Am* complexes.
corresponding NꢀH…O/NꢀH…N bond angles ranges from 152ºꢀ
176º, respectively. Interestingly, the shortest hydrogen bond
distances follow particular trend for C4TB…Am and C5TB…Am
complexes. That is, the shortest H…N hydrogen bond distance
found to be smaller compared to the shortest H…O hydrogen bond
in C4TB…Am complexes; however, such trend has been reversed
in cases of C5TB…Am complexes (see Table S2). The shorter
hydrogen bonding distances (H…O/H…N) correlate well with the
5
C4TB...Am
C5TB...Am
m =
gas
sol
gas
sol
1a
2
0.611
0.534
0.695
0.632
0.721
0.674
0.625
0.649
0.644
0.605
0.673
0.644
0.591
0.615
10 corresponding hydrogen bond donor (NꢀH) bond lengths. The
obtained computational results underpin the criteria of hydrogen
bond i.e., stronger the hydrogen bond weaker the Hꢀbond donor
0.558 (0.616)
0.572 (0.623)
0.556 (0.574)
0.483 (0.628)
0.590 (0.660)
0.489 (0.534)
0.503 (0.560)
0.489 (0.502)
0.428 (0.599)
0.535(0.595)
bond length (NꢀH).[14] Various orientations of CH3NH3 in
+
+
C4TB...CH3NH3 complex have been studied. The lowest energy
3
+
15 structure of (BE =34.43 kcal/mol) shows CH3NH3 sandwiched
between the crowns of C4TB (see SI).
4
5
Host-guest binding energy
This section describes the binding energies (BEs) of hostꢀguest
20 complexes in gasꢀphase (gas) as well as in solvent phase (sol)
obtained at M06ꢀ2X/ccꢀpVTZ//M06ꢀ2X/6ꢀ31G* level and the
results are shown in Figure 4. The calculated gasꢀphase binding
energies are approximately two and a half times higher than the
solventꢀphase BEs (Table S3). It is apparently clear that in gasꢀ
25 phase the charge transfer between host and guest, found to be
higher due to the absence of solvent effects and thus the higher
binding energy is observed in gasꢀphase calculations. Comparing
the BEs of C4TB…Am and C5TB…Am complexes, higher BEs
were observed for C5TB…Am complexes.
6
aThe initial folded conformation of A1 in C4TB-A1* complex collapsed to the
extended conformation (C4TB-A1) upon geometrical optimization.
In a few cases the BEs seem to decrease (Figure 4 & Table
50 S3) as increase in chain length of ‘Am’ observed from A1-A5 (for
C4TB…Am both gas & solution phases BEs and for C5TB…Am
gas BEs). The strength of A6 interaction with C4TB/C5TB found
to increase further as predicted by all methods. However, none of
the BE curves in Figure 4 explain the trend of association
55 constant (Ka) as a function of ‘Am’. To understand the contrast
between BEs and Ka trends, we have further explored the
bisammonium ion in folded conformation (‘Am*’, see Figure S1)
for binding with C4TB.
30
The minimum energy structure of C4TB…A1* complex was
60 not fixed on the potential energy surface (PES), since geometry
optimization of C4TB-A1* yields C4TB-A1, where A1 exits in
its extended form. Other five structures of C4TB…Am* (m = 2-
6) obtained as bisammonium ions with the folded conformations
(Am*). The BE calculations at M06ꢀ2X/ccꢀpVTZ//M06ꢀ2X/6ꢀ
65 31G* level have also been carried out for C4TB…Am*
complexes and taken up for the discussion. Interestingly, all
C4TB…Am* complexes shown higher BEs than the
corresponding C4TB…Am complexes (the difference is, for A2*
= 3.01 kcal/mol, A3* = 5.79 kcal/mol, A4* = 4.06 kcal/mol, A5*
70 = 11.68 kcal/mol and A6* = 10.51 kcal/mol). These results reveal
that the equilibrium between folded and extended conformation is
more towards folded conformation owing to the strong affinity of
folded bisammonium ions with the host molecule. More number
of gauge conformations of bisammonium ion leads to greater
75 affinity with the host molecule (C4TB) and thus the difference
increases from A2* to A6*.
Figure 4. The solventꢀphase binding energies (kcal/mol) of
C4TB…Am and C4TB...Am* complexes and the association
constant, Ka (Mꢀ1).
35
It can be stated that ‘bigger the crown size, higher the BE’ a
results similar to that observed in cationꢀπ interaction.[15] The
modulation of hostꢀguest BEs are not systematic upon increasing
size of bisammonium ions.
40
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10 binding energy into electrostatic (Ees), exchange repulsion (Ex),
polarization (POL) and charge transfer (CT). The POL and CT
terms are further divided into POLh, POLg, CThꢀg and CTgꢀh. The
EDA calculations on the supramolecular hostꢀguest complexes
are computationally cost. Therefore, we have used the more
15 compact truncated model systems for the EDA calculations, as
shown in Scheme 3.
The EDA results aid in delineating the role of various
components in modulating the binding strength upon increasing
alkyl chain length and increasing the crown ether size. It is also
20 important to scrutinize, why cationꢀπ interactions are not
preferred in the hostꢀguest complexes since, they are believed to
be the strong noncovalent interactions.[16] The EDA results shown
in Table 3, illustrate that, as alkyl chain length of ammonium ion
increases, the attractive components decrease systematically.
+
Scheme 3. The model systems considered in the study, M=NH4 .
+
+
+
Only for C4-M complex, M= NH4 , MeNH3 , EtNH3 and nPr–
+
NH3 .
5
25
The EDA calculations in Table 3 show that the increasing BE
as the crown ether (C4→C5) size increases is mainly due to the
reduction of repulsive interaction even though it appears to be
due to electrostatic component (see Table S6).
Energy decomposition analysis
Energy decomposition analysis (EDA) has become a useful
computational tool to decipher the role of various energy
components of hostꢀguest interaction. EDA splits the total
Table 3. The energy components of the hostꢀguest model systems considered. The values are reported in kcal/mol
CAHB
Cationꢀπ
+
+
+
+
+
+
+
BEꢀcomp
C4-Me–NH4
C4-Et–NH4
C4-n–Pr–NH4
C4-NH4
C5-NH4
TB1- NH4
TB2- NH4
Ees
Ex
63.13
ꢀ40.62
14.96
2.44
57.30
ꢀ37.77
12.42
2.62
54.63
ꢀ37.01
11.66
3.01
52.77
ꢀ37.51
10.93
2.80
73.08
ꢀ39.16
16.31
2.09
18.45
ꢀ11.76
10.05
0.10
12.42
ꢀ7.79
7.40
POLh
POLg
CThꢀg
CTgꢀh
Etot
0.11
11.18
0.53
9.24
8.81
9.04
10.15
0.47
6.62
4.50
0.60
0.55
0.54
0.16
0.09
51.61
44.4
41.64
38.58
62.94
23.62
16.73
30 The ‘h’ is for crown ether or tröger’s base and, ‘g’ is for the ammonium ion.
This was in line with the earlier report[17] i.e., the increasing BEs
flexibility of the host molecule. The incorporation of a flexible
of Li+ꢀpyridine (49 kcal/mol) to Li+ꢀpyridazine (57 kcal/mol) in 50 linker has a special role in selective binding of shorter chain
πꢀfashion, is mostly due to the reduction of repulsive component,
35 (Ex) .The EDA results given in Table 3, it is clear that, formation
of cationꢀπ interaction is less preferred compared to the CAHB
complexes due to the strong electrostatic interactions between
length bisammonium ions by overcoming the rigidity factor.
Further inꢀdepth computational studies rationalized the
experimental findings. Computational studies reveal that the
gauge conformations (folded) of flexible alkyl chain in hostꢀguest
host and guest molecules. Although the short range interactions 55 complexes lead strong binding with the host molecules and this is
like POL and CT components of BEs are higher in percentage
due to the higher charge transfer in hostꢀguest interaction. These
calculations also explain that the unusual higher binding constant
(Ka) of longer chain length bisammonium ions with the host
molecule, is due to the conformational folding of bisammonium
40 (Table S6) for cationꢀπ complexes larger Ees component of C4-
+
+
NH4 /C5-NH4 is the main factor for such propensity to form
CAHB hostꢀguest complexation over cationꢀπ complex
formation.
+
60 ions. The observed upfield shift of δ values in case of CH3NH3
is attributed to the sandwiched type complex.
Conclusions
45 In summary, two flexible ditopic Tröger’s base receptors
incorporating monoaza crown ethers have been designed and
synthesized for bisammonium ions recognition. Receptors bind
bisammonium ion of various chain lengths demonstrating that the
Experimental Section
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General Methods: All the starting materials were obtained from
commercial sources and used without further purification. Organic layers
were dried over anhydrous Na2SO4. TLC analyses were performed on
glass plates coated with silica gel 60 F254. Plates were visualized using
UV light (254 nm) and/or iodine. Column chromatography was
temperature for 48 h. After completion of the reaction (monitored by
60 TLC), reaction mixture was basified (pH = 8 to 9) with 25% aq. NH4OH
and the aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were dried over Na2SO4, concentrated in vacuo,
and purified by column chromatography to afford compound C4TB as
colourless foam in 12% yield (79 mg).
5
performed on silica gel (60×120 mesh) on a glass column. Melting points
1
(mp) were determined in capillary tubes and are uncorrected. H and 13C 65 Method B. Tröger’s base 5 (500 mg, 1.07 mmol) was added to the
NMR spectra (300, 500, 600 and 75 MHz respectively) were recorded
using TMS as an internal standard (0 ppm). Mass (ESI) data were
mixture of aza crown ether C4 (376 mg, 2.15 mmol) and K2CO3 (440 mg,
3.22 mmol) in 20 mL of acetonitrile. The reaction mixture was refluxed
for 36 h. After completion of the reaction (monitored by TLC) acetonitrile
was removed under reduced pressure. Water was added (30 mL), reaction
70 mixture was extracted with dichloromethane (3 × 50 mL) and combined
organic extracts were washed with water (3 × 20 mL). Solvent was
removed under reduced pressure, dried over Na2SO4 and purified by
column chromatography using 1:19 of NH4OH:MeOH to afford the
compound C4TB light brown foam in 68% yield (479 mg). 1H NMR (500
75 MHz, CDCl3): δ = 7.02 (d, J = 8.3 Hz, 2H), 6.72 (dd, J = 2.1, 9.4 Hz, 2H),
6.42 (d, J = 2.1 Hz, 2H), 4.61 (d, J = 17.7 Hz, 2H), 4.26 (s, 2H), 4.04 (d, J
= 16.6 Hz, 2H), 3.97 (t, J = 5.2, 6.2 Hz, 4H), 3.68ꢀ3.63 (m, 16H), 3.62 (t,
J=4.2, 5.2 Hz, 8H), 2.90 (t, J = 5.2, 6.2 Hz, 4H), 2.79 (t, J = 4.2 Hz, 8H);
13C NMR (75 MHz, CDCl3) δ = 155.1, 140.9, 128.6, 125.9, 114.4, 111.6,
10 recorded on quadruple mass spectrometry. HRMS data were obtained by
the ESI ionization sources. IR spectra were recorded on a FTIR
spectrometer as KBr pellets or neat.
Synthesis
of
10-(2-(4-nitrophenoxy)ethyl)-1,4,7-trioxa-10-
azacyclododecane (2)
15 To a mixture of aza crown ether C4 (1.0 g, 5.714 mmol) and K2CO3 (1.18
g, 8.57 mmol) in 30 mL of dry acetonitrile, 1ꢀ(2ꢀbromoethoxy)ꢀ4ꢀ
nitrobenzene 1 (1.41 g, 5.714 mmol) was added. Reaction was refluxed
for 7 days, after completion of the reaction (monitored by TLC), solvent
was removed under reduced pressure. Water was added (30 mL), reaction
20 mixture was extracted with dichloromethane (3 × 50 mL) and combined
organic extracts were washed with water (3 × 20 mL). Solvent was
removed under reduced pressure, dried over Na2SO4 and purified by 80 70.7, 70.1, 69.9, 67.1, 66.3, 58.8, 55.4, 55.3; IR (KBr, cmꢀ1) 2929, 1663,
column chromatography to afford the product 2 as light brown solid in
1591, 1337; MS (ESI) m/z (%) 657 ([M + H], 100), HRMS (ESI) calcd
o
1
68% yield (1.32 g), mp 79ꢀ80 C. H NMR (300 MHz, CDCl3) δ = 8.18
25 (d, J = 9.3 Hz, 2H), 6.95 (d, J = 9.3 Hz, 2H), 4.15 (t, J = 6.0 Hz, 2H),
for C35H53N4O8 657.38579, found 657.38765.
Synthesis
of
(5S,11S)-2,8-bis(2-(1,4,7,10-tetraoxa-13-
3.66ꢀ3.59 (m, 12H), 2.99 (t, J = 6.0 Hz, 2H), 2.81 (t, J = 4.7 Hz, 4H); 13
C
azacyclopentadecan-13-yl)ethoxy)-6,12-dihydro-5,11-
85 methanodibenzo[b,f][1,5]diazocine (C5TB)
NMR (75 MHz, CDCl3) δ = 163.7, 141.3, 125.8, 114.3, 70.9, 70.2, 67.3,
55.6, 55.1; IR (KBr, cmꢀ1) 2929, 1663, 1591, 1337; MS (ESI) m/z (%) 341
([M + H], 100), HRMS (ESI) calcd for C16H25N2O6 341.1712, found
30 341.1725.
Tröger’s base 5 (500 mg, 1.07 mmol) was added to the mixture of aza
crown ether C5 (470 mg, 2.15 mmol) and K2CO3 (440 mg, 3.22 mmol) in
20 mL of acetonitrile. The reaction mixture was refluxed for 36 h.
Acetonitrile was removed under reduced pressure. Water was added (30
90 mL), reaction mixture was extracted with dichloromethane (3 × 50 mL)
and combined organic extracts were washed with water (3 × 20 mL).
Solvent was removed under reduced pressure, dried over Na2SO4 and
purified by column chromatography using 1:19 of NH4OH:MeOH to
afford the compound C5TB as light brown foam in 74% yield (591 mg).
95 1H NMR (600 MHz, CDCl3): δ = 7.03 (d, J = 9.0 Hz, 2H), 6.72 (dd, J =
2.6, 9.0 Hz, 2H), 6.41 (d, J = 2.6 Hz, 2H), 4.62 (d, J = 16.6 Hz, 2H), 4.28
(s, 2H), 4.05 (d, J = 16.6 Hz, 2H), 3.94 (t, J = 6.0 Hz, 4H), 3.68ꢀ3.58 (m,
32H), 2.92 (t, J = 6.0 Hz, 4H), 2.84 (t, J = 6.0 Hz, 8H); 13C NMR (75
MHz, CDCl3) δ = 155.1, 140.9, 128.6, 125.9, 114.4, 111.6, 70.7, 70.1,
100 69.9, 67.1, 66.3, 58.8, 55.4, 55.3; IR (KBr, cmꢀ1) 2929, 1663, 1591, 1337;
MS (ESI) m/z (%) 745 ([M + H], 100), HRMS (ESI) calcd for
C39H61N4O10 745.43822, found 745.43909.
Synthesis
of
2,8-bis(2-bromoethoxy)-6,12-dihydro-5,11-
methanodibenzo[b,f][1,5]diazocine (5)
To a mixture of 4ꢀ(2ꢀbromoethoxy)aniline 4 (obtained by the –NO2
reduction of 1) (5 g, 23.1 mmol) in 20 mL ethanol, 50 mL of 37%
35 formaldehyde solution was added followed by 45 mL of concentrated
HCl (slow addition) at 0 oC. After HCl addition, the reaction mixture was
stirred at r. t. for 24 h. After completion of the reaction (monitored by
TLC), the mixture was concentrated under reduced pressure until one half
of the original volume remained and made basic with aq. NH4OH. The
40 aqueous phase was extracted with dichloromethane (3 × 100 mL). The
combined organic layers were washed with saturated NaHCO3 solution (2
× 100 mL) and dried over Na2SO4. The solvents were removed under
reduced pressure and purified by column chromatography using 30%
ethyl acetate in hexane as eluent afforded 5 in 27% yield (2.92 g) as a
45 white solid, mp 105ꢀ106 oC. 1H NMR (300 MHz, CDCl3): δ = 7.06 (d, J =
8.7 Hz, 2H), 6.75 (dd, J = 2.6, 8.9 Hz, 2H), 6.44 (d, J = 2.5 Hz, 2H), 4.64
(d, J = 16.6 Hz, 2H), 4.28 (s, 2H), 4.18 (t, J = 6.4 Hz, 4H), 4.07 (d, J =
16.8 Hz, 2H), 3.57 (t, J = 6.2 Hz, 4H); 13C NMR (75 MHz, CDCl3) δ =
154.4, 141.5, 128.7, 126.0, 114.6, 112.1, 68.0, 67.1, 58.8, 29.1; IR (neat,
50 cmꢀ1) 2936, 2882, 1486, 1265, 1151, 1034, 750; MS (ESI) m/z (%) 469
([M + H], 100), HRMS (ESI) calcd for C19H21N2O2Br2 466.99643, found
466.99695.
Experimental Procedure for NMR titrations
Accurately weigh receptor into a NMR tube and dissolved in 0.6 mL of
105 CD3OD. Then hosts were titrated by adding each time 1.0 mg of the guest
until no chemical shift change was observed for a distinguishable proton.
The concentration of substrate in CD3OD is varied from 0.25 equivalents
to 2 equivalents to the concentration of the receptor’s solution in CD3OD.
1H NMR spectra were recorded after each addition. The solvent signal
110 (CD3OD, 3.30 ppm) was used as reference peak. The chemical shift of the
bindicated proton(s) of hosts was used for calculating binding constants.
Synthesis of (5S,11S)-2,8-bis(2-(1,4,7-trioxa-10-azacyclododecan-10-
yl)ethoxy)-6,12-dihydro-5,11-methanodibenzo[b,f][1,5]diazocine
55 (C4TB)
Computational details
Method A. To a stirred mixture of 3 (obtained by the –NO2 reduction of
2) (310 mg, 1.0 mmol) and paraformaldehyde (90 mg, 3.0 mmol) TFA
The initial conformational search of host molecules (C4TB and C5TB)
have been done with discovery studio using Fast conformation module
115 between the energetics of 0.00 ꢀ 20.00 kcal/mol.[18] The obtained low
o
(10 mL) was added drop wise at ꢀ5 C. Stirring was continued at room
6
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 8
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C4OB02266A
a
Dr. A. Manjula, M. Bhaskar Reddy, M. Shailaja, Crop Protection
Chemicals Division, CSIRꢀIndian Institute of Chemical Technology,
Hyderabad, India, Eꢀmail: manjula@iict.res.in.
energy conformers of C4TB and C5TB were considered for building the
model structures of hostꢀguest complexes with set of six bisammonium
ions Am (m = 1-6) (Figure 2). The complexes C4TB…Am (m = 1-6) and
C5TB…Am (m = 1-6) and the simple model structures such as C4-
(NH4)+, C5-(NH4)+, TB1-(NH4)+, TB2-(NH4)+, C4-(CH3NH3)+, C4-
b Dr. G. N. Sastry, J. R. Premkumar, Centre for Molecular Modelling,
55 CSIRꢀIndian Institute of Chemical Technology, Hyderabad, India, Eꢀ
mail: gnsastry@iict.res.in.
5
c
(CH3CH2NH3)+ and C4-(CH3CH2CH2NH3)+ in Scheme
3 were
Dr. A. V. S. Sarma, K. Sirisha, Centre for Nuclear Magnetic
Resonance and Structural Chemistry, CSIRꢀIndian Institute of
Chemical Technology, Hyderabad, India.
optimized at PCMꢀM06ꢀ2X/6ꢀ31G(d) level of theory. The absence of
imaginary frequencies confirmed that all the structures were minima in
the potential energy surface at PCMꢀM06ꢀ2X/6ꢀ31G(d) level of theory.
1
60 Electronic Supplementary Information (ESI) available: H and 13C NMR
spectra of all new compounds, optimization structures at DFT level and
the cartesian coordinates are provided in the supporting information. See
DOI: 10.1039/b000000x/
10 The energetics of the dicationic complexes were further fine tuned by
improving the quality of the basis set. We used M06ꢀ2X[19] method and
the correlation consistent basis set with triple zeta quality ccꢀpVTZ[20] for
the binding energy calculations. The reported binding energies (BEs)
1
2
3
A. J. McConnell, P. D. Beer, Angew. Chem. Int. Ed. 2012, 51, 5052;
A. K. Mandal, M. Suresh, P. Das, A. Das, Chem. Eur. J. 2012, 18,
3906; M. Kruppa, B. König, Chem. Rev. 2006, 106, 3520; B. Linton,
A. D. Hamilton, Chem. Rev. 1997, 97, 1669; HꢀJ. Schneider, Angew.
Chem. Int. Ed. 1991, 30, 1417; A. S. Mahadevi, G. N. Sastry, Chem.
Rev. 2013, 113, 2100.
G. W. Gokel, W. M. Leevy, M. E. Weber, Chem. Rev. 2004, 104,
2723; K. Kimura, R. Mizutani, M. Yokoyama, R. Arakawa, Y.
Sakurai, J. Am. Chem. Soc. 2000, 122, 5448; H. Sakamoto, K.
Kimura, Y. Koseki, T. Shono, J. Chem. Soc. Perkin Trans 2 1987,
1181; C. J. Pedersen, J. Am. Chem. Soc. 1967, 89, 7017; J. M. Lehn,
Angew. Chem. Int. Ed. 1988, 27, 89ꢀ112.
A. Späth, B. König, Beilstein J. Org. Chem 2010, 6, 1; M. Sunkur, D.
Baris, H. Hosgoren, M. Togrul, J. Org. Chem. 2008, 73, 2570; G. W.
Gokel, W. M. Leevy, M. E. Weber, Chem. Rev, 2004, 104, 2723;
Y.Turgut, H. Hosgoren, Tetrahedron: Asymmetry 2003, 14, 3815; S.
K. Kim, M. Y. Bang, SꢀH. Lee, K. Nakamura, SꢀW. Cho, J. Yoon, J.
Inclusion Phenom. Macrocyclic Chem. 2002, 43, 71; W. S. Bryant, I.
A. Guzei, A. L. Rheingold, J. S. Merola, H. W. Gibson, J. Org.
Chem. 1998, 63, 7634; X. X. Zhang, J. S. Bradshaw, R. M. Izatt,
Chem. Rev. 1997, 97, 3313; P. R. Ashton, P. J. Campbell, E. J. T.
Crystal, P. T. Glink, S. Menzer, D. Philip, N. Spencer, J. F. Stoddart,
P. A. Tasker, D. J. Williams, Angew. Chem. Int. Ed. 1995, 34, 1865;
A. P. Silva, K. R. A. A. Sandanayake, Angew. Chem. Int. Ed. 1990,
29, 1173; M. Kim, G. Gokel, J. Chem. Soc., Chem. Commun. 1987,
1686.
65
70
were calculated by subtracting the total energy of the complex (Ecomplex
)
15 and the sum of the total energies of the individual fragments (Ehost and
Eguest) in their distorted environment. The BEs were calculated in three
ways as shown in the equations 2, 3 and 4. Here, Eguest* indicates that the
energy of the folded conformation bisammonium ion in the hostꢀguest
complex.
20
75
BE1 = [Ecomplex – (Ehost + Eguest)]
BE2 = [Ecomplex – (Ehost + Eguest*)]
BEavg = (BE1+BE2)/2
(2)
(3)
(4)
80
All the geometry optimization and the BEs calculations have been done
using Gaussian 09 program package.[21] The influence of bulk solvent
were included by means of PCM[22] considering methanol as a solvent.
The effect of solvation has been looked with various solvent with
25 dielectric constant 80.0 D (water) 47.0 D (DMSO) and 33.6 D (methanol)
for the C4-NH4+ system (see Table S5). The BEs of C4-NH4+ in presence
of water and in presence of methanol are found to be closer and the
difference is lower than 1.00 kcal/mol. Thus we have considered
‘Methanol’ for finding the solvent effect on supramolecular hostꢀguest
30 binding energy, since the difference between the dielectric constants of
‘Methanol’ and ‘Deuteratedꢀmethanol’ (33.7 D) is 0.1 D. Energy
decomposition analysis have been carried out using the reduced
variational space (RVS) technique implemented in the GAMESS program
package[23] at HF/6ꢀ31G(d) level of theory. This technique splits the
35 binding energy of a dimer into various components, such as electrostatic
(Ees), exchange repulsion (Ex), polarization (POL) and, charge transfer
(CT) components. The Ees component corresponds to the classical
electrostatic interaction between the unperturbed charge distributions of
the prepared fragments and it is usually attractive. The Ex term is the
40 energetic contribution arising from the repulsion between the occupied
molecular orbitals of the two fragments. The POL and CT components
are associated with the intramolecular and intermolecular orbital
relaxation energies of the two fragments. The POL and CT components
can be further divided into two individual components viz., POLg, POLh,
85
90
4
5
J. Tröger, J. Prakt. Chem. 1887, 36, 225.
M. A. Spielman, J. Am. Chem. Soc. 1935, 57, 583; E. Wagner, J. Am.
Chem. Soc. 1935, 57, 1296; T. R. Miller, E. C. Wagner, J. Am. Chem.
Soc. 1941, 63, 832; H. Rutter, J. Am. Chem. Soc., 1952, 74, 3434; M.
Häring, Helv. Chim. Acta 1963, 46, 2970.
95
6
C. S. Wilcox, Tetrahedron Lett. 1985, 26, 5749; I. Sucholeiki, V.
Lynch, L. Phan, C. S. Wilcox, J. Org. Chem. 1988, 53, 98; B. G.
Bag, U. Maitra, Synth. Commun. 1995, 25, 1849; H. Salez, A.
Wardani, M. Demeunynck, A. Tatibouet, J. Lhomme, Tetrahedron
Lett. 1995, 36, 1271; A. Hansson, J. Jensen, O. F. Wendt, K.
Warnmark, Eur. J. Org. Chem. 2003, 3179; Z. Li, X. Xu, Y. Peng, Z.
Jiang, C. Ding, X. Qian, Synthesis 2005, 1228; Z. Li, X. Xu, Y. Peng,
Z. Jiang, C. Ding, X. Qian, Synthesis 2005, 1230; S. Satishkumar, M.
Periasamy, Tetrahedron: Asymmetry 2006, 17, 1116; S. Satishkumar,
M. Periasamy, Tetrahedron: Asymmetry 2009, 20, 2257; T.
Kamiyama, M. S. Ozer, E. Otth, J. Deska, J. Vengros,
ChemPlusChem, 2013, 78, 1510ꢀ1516; M. B. Reddy, A. Manjula, B.
V. Rao, B. S. Sridhar, Eur. J. Org. Chem. 2012, 312; for reviews on
Tröger’s base see: Advances in Heterocyclic Chemistry by A. R.
Katritzky, 2007, 93, 1; S. Sergeyev, Helv. Chim. Acta 2009, 92, 415;
O. V. Runarsson, J. Artacho, K. Warnmark, Eur. J. Org. Chem. 2012,
7015; A. L. Whiting, K. I. Dubicki, F. Hof, Eur. J. Org. Chem. 2013,
6802; P. Ondrisek, R. Schwenk, J. Cvengros, Chem. Commun., 2014,
50, 9168.
100
105
110
115
120
45 CTgꢀh and CThꢀg
.
Acknowledgments
7
8
A. P. Hansson, P. O. Norrby, K. Warnmark, Tetrahedron Lett. 1998,
39, 4565; K. Kim, Jꢀ. I. Choe, Bull. Korean. Chem. Soc. 2006, 27,
1737.
C. S. Wilcox, M. D. Cowart, Tetrahedron Lett. 1986, 27, 5563; J. C.
Adrian, C. S. Wilcox, J. Am. Chem. Soc. 1989, 111, 8055; J. C.
Adrian, C. S. Wilcox, J. Am. Chem. Soc. 1991, 113, 678; T. H.
Webb, H. Suh, C. S. Wilcox, J. Am. Chem. Soc. 1991, 113, 8554; J.
C. Adrian, C. S. Wilcox, J. Am. Chem. Soc. 1992, 114, 1398; M. J.
Authors thank Director, IICT for facilities. MBR, JRP and KS thanks
CSIR, New Delhi for Fellowship. MS thanks DST for fellowship.
Financial support from NMB project at CSIRꢀIICT is acknowledged.
50 Notes and references
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

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Page 8 of 8
View Article Online
DOI: 10.1039/C4OB02266A
Crossley, T. W. Hambley, L. G. Mackay, A. C. Try, R. Walton, J.
Chem. Soc, Chem. Commun. 1995, 38, 4503; P. Rao, U. Maitra,
Tetrahedron Lett. 1996, 37, 5791; S. Goswami, K. Ghosh,
Tetrahedron Lett. 1997, 38, 4503; A. Manjula, M. Nagarajan,
Tetrahedron 1997, 53, 11859; Eꢀ. Kim, S. Paliwal, C. S. Wilcox, J.
Am. Chem. Soc. 1998, 120, 11192; J. N. H. Reek, A. P. H. J.
Schenning, A. W. Bosman, E. W. Meijer, M. J. Crossley, Chem.
Commun. 1998, 11; S. Goswami, K. Ghosh, S. Dasgupta, J. Org.
Chem. 2000, 65, 1907; M. Miyake, C. S. Wilcox, Heterocycles 2002,
57, 515; T. Kobayashi, T. Moriwaki, Heterocycles 2004, 62, 399; M.
Valik, R. M. Strongin, V. Kral, Supramol. Chem. 2005, 17, 347; J.
Artacho, E. Ascic, T. Rantanen, C. ꢀJ. Wallentin, S. Dawaigher, KꢀE.
Bergquist, M. Harmata, V. Snieckus, K. Warnmark, Org. Lett. 2012,
14, 4706; Thio: E. M. Boyle, S. Comby, J. K. Molloy, T.
Gunnlaugsson, J. Org. Chem. 2013, 78, 8312; M. Yamada, K.
Tokutomi, A. Takehara, Y. Sakai, Y. Maeda, T. Hasegawa,
Fullerenes, Nanotubes, Carbon Nanostruct.2014, 22, 66.
5
10
15
20
25
30
35
9
Kꢀ. M. Park, H. J. Kim, SꢀH. Moon, J. J. Vittal, J. H. Jung, S. S. Lee,
New J. Chem. 2010, 34, 603; P. Hurtado, F. Gámez, S. Hamad, B. Mꢀ
. Haya, J. D. Steill, J. Oomens, J. Phys. Chem. A 2011, 115, 7275.
10 K. E. Krakowiak, J. S. Bradshaw, D. J. Z. –Krakowiak, Chem. Rev.
1989, 89, 929.
11 L. Fielding, Tetrahedron 2000, 56, 6151; Z. Ding, H. Wing, X.
Liang, E. R. Morris, F. Gallazzi, S. Pandit, J. Skolnick, J. C. Walker,
S. R. V. Doren, Biochemistry 2007, 46, 2684.
12 P. R. Ashton, E. J. T. Crystal, P. T. Glink, S. Menzer, C. Schiavo, N.
Spencer, J. F. Stoddart, P. A. Tasker, A. J. P. White, D. J. Williams,
Chem. Eur. J. 1996, 2, 709; S. J. Schneider, R. Kramer, S. Simova,
U. Schneider, J. Am. Chem. Soc. 1988, 110, 6442; E. Fan, S. A. V.
Arman, S. Kincaid, A. D. Hamilton, J. Am. Chem. Soc. 1993, 115,
369ꢀ370.
13 M. R. Johnson, N. F. Jones, I. O. Sutherland, J. Chem. Soc. Perkin
Trans 1 1985, 1637.
14 E. Arunan, G. R. Desiraju, R. A. Klein, J. Sadlej, S. Scheiner, I.
Alkorta, D. C. Clary, R. H. Crabtree, J. J. Dannenberg, P. Hobza, H.
G. Kjaergaard, A. C. Legon, B. Mennucci, D. J. Nesbitt, Pure Appl.
Chem. 2011, 83, 1637.
15 J. R. Premkumar, D. Vijay, G. N. Sastry, Dalton Trans. 2012, 41,
4965.
40 16 A. S. Reddy, G. N. Sastry, J. Phys. Chem. A 2005, 109, 8893.
17 B. Sharma, D. Umadevi, G. N. Sastry, Phys. Chem. Chem. Phys.
2012, 14, 13922.
18 Accelrys Software Inc., Discovery Studio Modeling Environment,
Release 2.5.5, San Diego: Accelrys Software Inc., 2007.
45 19 Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215.
20 T. H. Dunning, Jr., J. Chem. Phys. 1989, 90, 1007; R. A. Kendall, T.
H. Dunning, Jr., R. J. Harrison, J. Chem. Phys. 1992, 96, 6796.
21 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A.
50
55
60
Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F.
Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, J. E.
Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N.
Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K.
Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M.
Cossi, N. Rega, N. J. Millam, M. Klene, J. E. Knox, J. B. Cross, V.
Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O.
Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L.
Martin, K. Morokuma, V. G. Zakrzewski, G. S. Voth, P. Salvador, J.
J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09,
Revision A.02, Gaussian, Inc., Wallingford, CT, 2009.
22 E. Cances, B. Mennucci, J. Tomasi, J. Chem. Phys. 1997, 107, 3032.
65 23 M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S.
Gordon, J. J. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. Su,
T. L. Windus, M. Dupuis and J. A. Montgomery, J. Comput. Chem.
1993, 14, 1347.
70
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