Host–guest interactions between hemicucurbiturils and a hydroxyl-substituted Schiff base

Article abstract of DOI:10.1007/s10847-016-0659-3

The host–guest interactions of hemicucurbit[6 and 12]urils with the Schiff base guest 1 has been investigated. ¹H NMR spectra suggest hemicucurbit[6 and 12]urils bind to guest 1 with the formation of hydrogen bondings between the phenol hydroxyl group and carbonyl groups in the host. The formation of interaction complexes are also supported by fluorescence emission spectroscopy. The moderate association constants of the interaction complexes in a ratio of 1:1 are obtained to be (3.2?±?0.6)?×?10⁵ and (5.5?±?0.8)?×?10⁵?L?mol^?1, respectively, via non-linear curve fitting, which indicate that the formation of hydrogen bondings are important in the host–guest interactions.

Full text of DOI:10.1007/s10847-016-0659-3

J Incl Phenom Macrocycl Chem
DOI 10.1007/s10847-016-0659-3
ORIGINAL ARTICLE
Host–guest interactions between hemicucurbiturils
and a hydroxyl-substituted Schiff base
Xian-Yi Jin1 Fang Wang1 Hang Cong1 Zhu Tao1
•
•
•
Received: 18 July 2016 / Accepted: 12 September 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract The host–guest interactions of hemicucurbit[6
and 12]urils with the Schiff base guest 1 has been investi-
gated. 1H NMR spectra suggest hemicucurbit[6 and 12]urils
bind to guest 1 with the formation of hydrogen bondings
between the phenol hydroxyl group and carbonyl groups in
the host. The formation of interaction complexes are also
supported by fluorescence emission spectroscopy. The
moderate association constants of the interaction complexes
in a ratio of 1:1 are obtained to be (3.2 0.6) 9 105 and
(5.5 0.8) 9 105 L mol-1, respectively, via non-linear
curve fitting, which indicate that the formation of hydrogen
bondings are important in the host–guest interactions.
glycoluril units linked together with a pair of methylene
bridges [6]. New members of the cucurbituril family (Q[n],
n = 5–8, 10 and 14) with different degrees of oligomerization
and their supramolecular properties have been developed to
provide a platform in supramolecular chemistry [7].
Hemicucubit[n]urils (HemiQ[n], n = 6 and 12) were dis-
covered in 2004 by Miyahara et al. [8] and lead to the devel-
opment of a sub-group of cucurbituril chemistry, including
members such as bambusuils, cyclohexylhemicucurbiturils,
biotin[6]urils and norbornahemicucurbit[6]uril [9–15], which
have been applied to the molecular recognition of anions,
supramolecular catalysis and the preparation of transmem-
branes for anion transport [10, 16–20].
Keywords Hemicucurbituril Á Schiff base Á
Supramolecular chemistry Á Host–guest interaction Á
Molecular recognition
The chemistry of Schiff bases has attracted the attention
of scientists for many decades, which is mainly due to their
desirable chemical nature [21, 22]. Due to their various
structures and wide range of uses, Schiff bases have
important potential applications and have been applied as
magnetic [23], antibacterial [24], fluorescent [25] and cat-
alytic compounds [26]. Hydroxyl-substituted Schiff bases
have received considerable attention due to their potential
anticancer activity [27]. In this work, we have designed,
synthesized and characterized the Schiff base guest 1, and
investigated its interactions with HemiQ[6 and 12]uril
(Scheme 1). To explore the HemiQs’ influence on the
Schiff base’s optical properties, we have preliminary
explored the regularities of the host–guest interactions
between the HemiQs and guest 1.
Introduction
Macrocyclic molecules, which often serve as receptors in
supramolecular chemistry, often afford useful applications in
manyareas [1–4]. Behrend synthesized the firstcucurbiturilin
1905 [5] and its structure was characterized by Mock et al.,
which was found to be a very rigid macrocycle made of
Electronic supplementary material The online version of this
article (doi:10.1007/s10847-016-0659-3) contains supplementary
material, which is available to authorized users.
& Hang Cong
Results and discussion
ecnuc@163.com
1
The H NMR resonance signals of guest 1 are assigned in
Fig. 1a and one can see that the resonance signals in the
1
Key Laboratory of Macrocyclic and Supramolecular
Chemistry of Guizhou Province, Guizhou University,
Guiyang 550025, People’s Republic of China
chemical shift range from d = 6.87 to 7.80 ppm are
123

J Incl Phenom Macrocycl Chem
Scheme 1 Synthesis of the
hydroxyl substituted
O
Ethanol
O
N
N
dibenzylidenehydrazine guest 1
and simulated structures of
hemicucurbit[6 and 12]urils
with a semi-empirical method of
PM6-D3H4, color codes: grey,
carbon; blue, nitrogen; red,
oxygen. (Color figure online)
+
+
H2NNH2
Refluxing
H
O
H
O
1
Hemicucurbit[6]uril
Hemicucurbit[12]uril
1
Fig. 1 The H NMR spectra of a guest 1 and guest 1 in the presence of b hemicucurbit[6]uril and c hemicucurbit[12]uril
assigned to the protons on the aromatic ring of guest 1,
which show almost no change after the addition of the host
HemiQ[6 or 12] (Fig. 1b, c). The resonance signals at 8.64
and 8.80 ppm are assigned to the protons on the amine
groups (H6 and H8) and no significant change in the
chemical shift was observed in the presence of the
macrocyclic compounds. However, the proton resonance
corresponding to the phenol hydroxyl group, which appears
as a singlet at d = 11.4 ppm produces a new singlet at
11.1 ppm upon the addition of either HemiQ[6] or
HemiQ[12], which implies the formation of stable host–
guest interaction complexes between guest 1 and HemiQ[6
or 12] with the formation of hydrogen bonding between the
hydroxyl group on the guest and the carbonyl groups in the
hemicucurbiturils [18].
The host–guest interactions between hemicucurbiturils
and guest 1 were also investigated by fluorescence titra-
tions. In Fig. 2a, the fluorescence emission of 1 appeared at
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J Incl Phenom Macrocycl Chem
501 nm upon excitation at 397 nm. The fluorescence
intensity was gradually decreased upon the addition of
HemiQ[6] (Fig. 2b), while the intensity kept constant when
the CHemiQ[6]:Cguest ratio was 1:1. An association constant
the macrocycle (Fig. 3a). The intensity decrease upon on
the addition this amount of HemiQ[12] suggests a host–
guest interaction ratio of 1:1 (Fig. 3b), which is similar to
the interaction system between guest 1 and HemiQ[6].
Furthermore, the interaction ratio of guest 1 to hemicu-
curbit[12]uril was also found to be 1:1 using the Job’s plots
obtained from the fluorescence spectra(Fig. S3, ESI). By
non-linear least square fitting using Eq. (1), the association
constant (Ka) was obtained to be (5.5 0.8) 9 105
L mol-1 (Fig. S4, ESI), which is obvious bigger than that
in the case of the interaction between guest 1 and
HemiQ[6], therefore, the higher affinity of HemiQ[12] to
guest 1 implies there is other driving force than the for-
mation of hydrogen bonding. A hydrogen bonding of 2.62
(Ka) of (3.2 0.6) 9 105 L mol-1 for guest
1 at
HemiQ[6] was obtained via non-linear fitting (Fig. S1,
ESI). Moreover, the 1:1 ratio of host–guest interaction of
HemiQ[6] with guest 1 was also confirmed by the Job’s
plots obtained from the fluorescence spectra (Fig. S2, ESI).
The molecular simulation provides a hydrogen bonding of
˚
1.84 A between HemiQ[6] and guest 1, and the relative
small cavity of host restrains the encapsulation of guest
[28], therefore, the Schiff base guest stays at the portal to
form an exclusion complex in a ratio of 1:1 (Fig. 2c).
In the case of the HemiQ[12] host, the fluorescence
titrations also support the formation of its host–guest
interactions with guest 1 with the decreasing fluorescence
intensity observed in the presence of different amounts of
the host that become stable after the addition of 1 equiv of
˚
A between HemiQ[12] and guest 1 is also observed in the
simulated structure (Fig. 3c), and the bigger cavity of host
macrocycle allows the formation of an encapsulation
complex in a ratio of 1:1, interestingly, hemicucur-
bit[12]uril with more flexible structure is twisted to match
Fig. 2 a The emission spectra (kem = 501 nm excited at kex = 397
nm) of guest 1 (2.5 9 10-5 mol L-1 upon the addition of an
increasing amount of HemiQ[6] from 0 to 2 equiv. in CHCl3/CH3OH
(1:1); b The fluorescent intensity at 501 nm of guest 1 (2.5 9 10-5
mol L-1 upon the addition of an increasing amount of HemiQ[6]
from 0 to 2 equiv. in CHCl3/CH3OH (1:1); c The energy minimized
structure of interaction complex of HemiQ[6] with guest 1 with a
semi-empirical method of PM6-D3H4, color code: grey, carbon; blue,
nitrogen and red, oxygen; white, hydrogen. (Color figure online)
123

J Incl Phenom Macrocycl Chem
fluorescence intensity, which should be the result of the
formation of hydrogen bonding as found in the analysis of
1
the interactions using H NMR spectroscopy. It is well
known that intramolecular proton transfer from the
hydroxyl group to the imino nitrogen atom occurs in
ortho-hydroxyl substituted Schiff base compounds
[29–31] and in the presence of hemicucurbiturils, the
intramolecular proton transfer of guest 1 should be
restrained due to the formation of hydrogen bonding
between the hydroxyl group in the guest molecule and the
carbonyl groups in the hosts, which then leads photo-
induced electron transfer from the nitrogen atom in the
imino group to the aromatic ring and results in the
decrease in fluorescence intensity.
To understand the important role of the hydroxyl group
in the host–guest interactions, another Schiff base, 1,2-
dibenzylidenehydrazine, was subjected to the host–guest
interactions with hemicucurbit[6 and 12]urils, and as
1
expected, the results obtained from both H NMR spec-
troscopy and fluorescence spectroscopy show no interac-
tions
between
the
HemiQs
and
the
1,2-
dibenzylidenehydrazine substrate (Figs. S4, S5, ESI).
Therefore, it was proposed that the formation of the inter-
actions in complexes of guest 1 with HemiQ[6 and 12] was
through hydrogen bonding between the phenol hydroxyl
group to the macrocyclic hosts.
Conclusions
In summary, the host–guest interactions of hemicucurbit[6
and 12]urils with a Schiff base guest 1 have been investi-
gated using 1H NMR spectroscopy and fluorescence
1
emission spectroscopy. The results obtained from the H
NMR spectra suggest guest 1, the ortho-hydroxyl substi-
tuted Schiff base, interacts with HemiQ[6 and 12] via the
formation of hydrogen bonding between the phenol
hydroxyl group and carbonyl groups in the host. Fluores-
cence emission spectroscopy revealed that the formation of
the interaction complexes of guest 1 with hemicucurbit[6
and 12]uril were in a ratio of 1:1 with moderate association
constants of (3.2 0.6) 9 105 L mol-1 (for the HemiQ[6]
host) and (5.5 0.8) 9 105 L mol-1 (for the HemiQ[12]
host), respectively. The simulated structures of the inter-
action complexes suggest two different interaction models,
that is, exclusion complex forms between HemiQ[6] and
guest 1, and the guest could be encapsulated by hemicu-
curbit[12]uril. Another synthetic guest, 1,2-dibenzylidene-
hydrazine, was also subjected to the host–guest system and
the lack of observed interactions indicate that the phenol
hydroxyl group was important in the binding of guest 1 to
the hemicucurbiturils.
Fig. 3 a The emission spectra (kem = 501 nm excited at kex = 397
nm) of guest 1 (2.5 9 10-5 mol L-1 upon the addition of an
increasing amount of HemiQ[12] from 0 to 2 equiv. in CHCl3/CH3OH
(1:1); b The fluorescent intensity at 501 nm of guest 1 (2.5 9 10-5
mol L-1 upon the addition of an increasing amount of HemiQ[12]
from 0 to 2 equiv. in CHCl3/CH3OH (1:1); c The energy minimized
structure of interaction complex of HemiQ[12] with guest 1 with a
semi-empirical method of PM6-D3H4, color code: grey, carbon; blue,
nitrogen and red, oxygen; white, hydrogen. (Color figure online)
the guest geometrically, which could offer the extra sta-
bility in the host–guest interaction.
The host–guest interactions of guest 1 with HemiQ[6
and 12] have been supported by the decrease in the
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J Incl Phenom Macrocycl Chem
163.64 ppm. ESI–MS (m/z), [M?H?]: calc. 225.1; found
225.1.
Experimental
1,2-Dibenzylidenehydrazine: A solution of benzaldehyde
Materials and apparatus
(2.6 g,
24 mmol)and
hydrazine
hydrate(0.75 mL,
12 mmol)in ethanol (25 mL)was heated at reflux for 5 h and
then cooled to room temperature to provide a yellow crystal
precipitate that was collected by filtration to give the desired
product(2.45 g) in 98 % yield. 1H NMR (400 MHz, DMSO-
d6): d 7.53(d, 2 H, J = 8.0 Hz), 7.55(m, 4 H, J = 8.0 Hz),
7.92(d, 4 H, J = 8.0 Hz), 8.75(s, 2 H) ppm [33].
The HemiQ[n] (n = 6 or 12) samples were prepared and
purified according to a literature method [8] and were
characterized by 1H NMR spectroscopy. HemiQ[6]
(CDCl3, d): 3.38 (s, 24 H), 4.68 (s, 12 H) ppm; HemiQ[12]
(CDCl3, d): 3.40 (s, 48 H), 4.68 (s, 24 H) ppm. Salicy-
laldehyde, benzaldehyde and hydrazine hydrate were
obtained commercially and used without further purifica-
1
Fluorescence measurements of the host–guest
interactions
tion. H NMR spectra were recorded at 22 °C on a VAR-
IAN INOVA-400 spectrometer using SiMe4 as an internal
reference in a mixture of CDCl3/CD3OD (1:1, v/v). UV–
Vis absorption spectra were recorded on a Unico UV-2102
instrument. Fluorescence absorption spectra of the guest
molecule and the host–guest complexes were recorded on a
Varian RF-540 fluorescence spectrophotometer at 25 °C.
All calculations have been processed with MOPAC 2016
software package. The semi-empirical method of PM6-
D3H4, PM6 with corrected dispersion and hydrogen bond
terms using the D3H4 method, was used for full geometry
optimization.
Fluorescence titrations were carried in a mixed solution of
CHCl3 and CH3OH (1:1, v/v) and the guest was prepared at a
fixed concentration of 2.5 9 10-5 mol L-1. The solution
was combined with HemiQ[n] (n = 6 or 12) in Chost:C1
ratios of 0, 0.25:1, 0.5:1, 0.75:1, 1:1, etc. For the Job plots, the
total concentration of (Chost ? C1) was 2.5 9 10-5
mol L-1. All fluorescence measurements were carried out
with an emission wavelength at k = 502 nm and an exci-
tation wavelength at k = 397 nm. The association constants
of the host–guest interactions were obtained via non-linear
fitting using Eq. (1):
qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
2
Dað½HŠ0 þ ½GŠ0 þ 1=KaÞ Æ
Da2ð½HŠ0 þ ½GŠ0 þ 1=KaÞ À 4Da2½HŠ ½GŠ
0
0
DI ¼
ð1Þ
2
Preparation of the guest molecules
where DI is the change in the fluorescence intensity of guest 1
upon the gradual addition of HemiQ[6 or 12] and Da refers to
the difference in the proportionality constant between the
free guest and the interaction complex. The total concen-
tration of the host and guest are denoted by [H]0 and [G]0,
respectively [34].
Guest 1: 1 was synthesized according to a literature method
[32]. To a stirred solution of salicylaldehyde (1.5 g,
12 mmol) and benzaldehyde (1.3 g, 12 mmol) in ethanol
(25 mL), a solution of hydrazine hydrate (0.75 mL,
12 mmol) in ethanol (5 mL) was added dropwise. The
solution was refluxed for 5 h, cooled to room temperature,
the solvent distilled under reduced pressure and the
resulting residue purified by column chromatography (sil-
ica gel; eluent: ethyl acetate/normal hexane 5:1) to afford a
yellow solid. The yellow solid was dried under vacuum to
give compound 1 (0.83 g) in 31 % yield. 1H NMR
(400 MHz, DMSO-d6): d 6.98(t, 1 H, J = 8.0 Hz), 6.99(d,
1 H, J = 8.0 Hz), 7.40(t, 1 H, J = 8.0 Hz), 7.52(t, 1 H,
J = 8.0 Hz), 7.54(t, 2 H, J = 8.0 Hz), 7.70(d, 1 H,
J = 8.0 Hz), 7.89(d, 2 H, J = 4.0 Hz), 8.82(s, 1 H),
8.97(s, 1 H), 11.3(s, 1 H) ppm. 13C NMR (400 MHz,
DMSO-d6) d 116.94, 118.64, 120.00, 128.94, 129.43,
131.69, 132.06, 133.53, 134.02, 159.19, 162.80,
Acknowledgments We acknowledge the financial support of
National Natural Science Foundation of China (No. 21662007), the
Project of Talent Introduction of Guizhou University (No. (2014)24).
References
1. Ghale, G., Nau, W.M.: Dynamically analyte-responsive macro-
cyclic host-fluorophore systems. Acc. Chem. Res. 47, 2150–2159
(2014)
2. Canevet, D., Gallego, M., Isla, H., de Juan, A., Perez, E.M.,
Martin, N.: Macrocyclic hosts for fullerenes: extreme changes in
binding abilities with small structural variations. J. Am. Chem.
Soc. 133, 3184–3190 (2011)
123

J Incl Phenom Macrocycl Chem
3. Liu, X., Weinert, Z.J., Sharafi, M., Liao, C., Li, J., Schneebeli,
S.T.: Regulating molecular recognition with C-shaped strips
attained by chirality-assisted synthesis. Angew. Chem. Int. Ed.
54, 12772–12776 (2015)
4. Chen, H., Fan, J., Hu, X., Ma, J., Wang, S., Li, J., Yu, Y., Jia, X.,
Li, C.: Biphen[n]arenes. Chem. Sci. 6, 197–202 (2015)
5. Behrend, R., Meyer, E., Rusche, F.: Over condensation products
from glycoluril and formaldehyde. [machine translation]. Liebigs
Ann. Chem. 339, 1 (1905)
transmembrane anion carriers employing C–H… anion interac-
tions. J. Am. Chem. Soc. 137, 4948–4951 (2015)
21. Zabierowski, P., Szklarzewicz, J., Kurpiewska, K., Lewinski, K.,
Nitek, W.: Assemblies of substituted salicylidene-2-ethanolamine
copper(II) complexes: from square planar monomeric to octahe-
dral polymeric halogen analogues. Polyhedron 49, 74–83 (2013)
22. Guptak, C., Sutar, A.K.: Catalytic activities of Schiff base tran-
sition metal complexes. Coord. Chem. Rev. 252, 1420–1450
(2008)
´
6. Mock, W.L., Shih, N.Y.: Host–guest binding capacity of cucur-
bituril. Org. Chem. 48, 3618 (1983)
7. Cong, H., Ni, X.L., Xiao, X., Huang, Y., Zhu, Q.J., Xue, S.F.,
Tao, Z., Lindoy, L.F., Wei, G.: Synthesis and separation of
cucurbit[n]urils and their derivatives. Org. Biomol. Chem. 14,
4335–4364 (2016)
8. Miyahara, Y., Goto, K., Oka, M., Inazu, T.: Remarkably facile
ring-size control in macrocyclization: synthesis of hemicucur-
bit[6]uril and hemicucurbit[12]uril. Angew. Chem. Int. Ed. 43,
5019–5022 (2004)
9. Svec, J., Necas, M., Sindelar, V.: Bambus[6]uril. Angew. Chem.
Int. Ed. 49, 2378–2381 (2010)
23. Nayak, S., Aromı, G., Teat, S.J., Ribas-Arin˜o, J., Gamez, P.,
Reedijk, J.: Hydrogen bond assisted co-crystallization of a
bimetallic Mn(III)2Ni(II)2 cluster and a Ni(II)2 cluster unit:
synthesis, structure, spectroscopy and magnetism. Dalton Trans.
39, 4986–4990 (2010)
24. Badwaik, V.B., Deshmukh, R.D., Aswar, A.S.: Transition metal
complexes of a Schiff base: synthesis, characterization, and
antibacterial studies. J. Coord. Chem. 62, 2037–2047 (2009)
25. Bunzli, J.C.-G., Piguet, C.: Lanthanide-containing molecular and
supramolecular polymetallic functional assemblies. Chem. Rev.
102, 1897–1928 (2002)
26. Cay, S., Kose, M., Tumer, F., Golcu, A., Tumer, M.: SOD
activity and DNA binding properties of a new symmetric por-
phyrin Schiff base ligand and its metal complexes. Spectrochim.
Acta A 151, 821–838 (2015)
10. Yawer, M.A., Havel, V., Sindelar, V.: A bambusuril macrocycle
that binds anions in water with high affinity and selectivity.
Angew. Chem. Int. Ed. 54, 276–279 (2015)
¨
¨
¨ ¨
11. Li, Y., Li, L., Zhu, Y., Meng, X., Wu, A.: Solvent effect on
pseudopolymorphism of hemicyclohexylcucurbit[6]uril. Cryst.
Growth Des. 9, 4255–4257 (2009)
27. Kose, M., Ceyhan, G., Tumer, M., Demirtas, I., Gonul, I.,
McKee, V.: Monodentate Schiff base ligands: their structural
characterization, photoluminescence, anticancer, electrochemical
and sensor properties. Spectrochim. Acta A 137, 477 (2015)
28. Xiang, D.D., Geng, Q.X., Cong, H., Tao, Z., Yamato, T.: Host–
guest interaction of hemicucurbiturils with phenazine
hydrochloride salt. Supramol. Chem. 27, 37–43 (2015)
¨
ˇ
12. Prigorchenko, E., Oeren, M., Kaabel, S., Fomitsenko, M., Reile,
´
¨
I., Jarving, I., Tamm, T., Topic, F., Rissanenc, K., Aav, R.:
Template-controlled synthesis of chiral cyclohexylhemicucur-
bit[8]uril. Chem. Commun. 51, 10921–10924 (2015)
´
´
´
13. Lisbjerg, M., Jessen, B.M., Rasmussen, B., Nielsen, B.E., Mad-
sen, A.Ø., Pittelkow, M.: Discovery of a cyclic 6 ? 6 hexamer of
D-biotin and formaldehyde. Chem. Sci. 5, 2647–2650 (2014)
14. Lisbjerg, M., Nielsen, B.E., Milhøj, B.O., Sauer, S.P.-A., Pit-
telkow, M.: Anion binding by biotin[6]uril in water. Org. Biomol.
Chem. 13, 369–373 (2015)
29. Jimenez-Sanchez, A., Farfan, N., Santillan, R.: Multiresponsive
photo-, solvato-, acido-, and ionochromic Schiff base probe.
J. Phys. Chem. C 119, 13814–13826 (2015)
30. Naik, A.D., Fontaine, G., Bellayer, S., Bourbigot, S.: Crossing the
traditional boundaries: salen-based Schiff bases for thermal pro-
tective applications. ACS Appl. Mater. Interfaces. 7,
21208–21217 (2015)
31. Li, S.Y., Wang, X.B., Kong, L.Y.: Design, synthesis and bio-
logical evaluation of imine resveratrol derivatives as multi-tar-
geted agents against Alzheimer’s disease. Eur. J. Med. Chem. 71,
36–45 (2014)
15. Fiala, T., Sindelar, V.: Synthesis of norbornahemicucurbiturils.
Synlett 24, 2443–2445 (2013)
´
16. Aav, R., Shmatova, E., Reile, I., Borissova, M., Topic, F., Ris-
sanen, K.: New chiral cyclohexylhemicucurbit[6]uril. Org. Lett.
15, 3786–3789 (2013)
17. Cong, H., Yamato, T., Feng, X., Tao, Z.: Supramolecular catal-
ysis of esterification by hemicucurbiturils under mild conditions.
J. Mol. Catal. A: Chem. 365, 181–185 (2012)
32. Lokhande, P.D., Raheem, A., Sabale, S.T., Chabukswar, A.R.,
Jageale, S.C.: An efficient synthesis of 1-H indazoles. Tetrahe-
dron Lett. 48, 6890–6892 (2007)
18. Cong, H., Yamato, T., Tao, Z.: Chemo-selective oxidation of
hydroxybenzyl alcohols with IBX in the presence of hemicu-
curbit[6]uril. New J. Chem. 37, 3778–3783 (2013)
19. Cong, H., Yamato, T., Tao, Z.: Hemicucurbit[6]uril-induced
aerobic oxidation of heterocyclic compounds. J. Mol. Catal. A:
Chem. 379, 287–293 (2013)
33. Bartholomaeus, P., Toma, G., Oliver, K.C.: Continuous flow
reduction of artemisinic acid utilizing multi-injection strategies—
closing the gap towards a fully continuous synthesis of anti-
malarial drugs. Chem. A Eur. J. 21, 4368–4376 (2015)
34. Thordarson, P.: Determining association constants from titration
experiments in supramolecular chemistry. Chem. Soc. Rev. 40,
1305–1323 (2011)
20. Lisbjerg, M., Valkenier, H., Jessen, B.M., Al-Kerdi, H., Davis,
A.P., Pittelkow, M.: Biotin[6]uril esters: chloride-selective
123