Anion binding by tert-butanesulfinamide based phenol receptors

Article abstract of DOI:10.1016/j.tetlet.2015.12.090

A series of tert-butanesulfinamide type compounds, which were decorated with phenol receptors, were found to recognize chlorine ion, nitrate ion, and acetate ion by ¹H NMR titration experiments. The results indicated that the interaction betwee

Full text of DOI:10.1016/j.tetlet.2015.12.090

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Anion binding by tert-butanesulfinamide based phenol receptors
a,
Ye-Ye Shen a,y, Yao Li a,y, Bin Wang b, , Xin Li
⇑
⇑
a State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Department of Chemistry, Nankai University,
Tianjin 300071, PR China
b Tianjin Key Laboratory of Structure and Performance for Functional Molecule, College of Chemistry, Tianjin Normal University, Tianjin 300387, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of tert-butanesulfinamide type compounds, which were decorated with phenol receptors, were
found to recognize chlorine ion, nitrate ion, and acetate ion by 1H NMR titration experiments. The results
indicated that the interaction between subject molecule and anion was enhanced with the increase of the
acidity of the phenolic O–H group. Furthermore, the tert-butyl group seemed to play a role in the anion
recognition.
Received 21 October 2015
Revised 9 December 2015
Accepted 23 December 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
tert-Butanesulfinamide
Phenol
Anion recognition
Hydrogen-bond donor
O–H group
Anions, such as chloride, nitrate, acetate, phosphate, and sulfate
ion, play important roles in the areas of biological, medical, envi-
ronmental, and life science.1 In general, the functions of anions
are achieved by recognition between a substrate and anion. There-
fore, the study of the recognition of anions has moved on from
being an area solely of academic interest to a fundamental pillar
of supramolecular chemistry and attracted great attention.2 Fur-
thermore, the anion recognition has also been used to develop a
very efficient organocatalytic strategy, ie anion-binding catalysis,
which realized a number of challenge organic transformations.3
As is known, featuring the molecular complementarity of the two
partners, highly specific anion binding may occur through a series
of multifarious noncovalent interactions, such as electrostatic,
hydrophobic, hydrogen-bonding, and anion-interactions.4 Based
on the various associative interactions, plenty of subject molecules
have been designed and synthesized for the application in anion
recognition, transport, sensing, and extraction.5 Among them,
hydrogen bond type compounds, by virtue of their diversity and
modification of structure and convenient synthesis, have become
the most widely studied anion receptors.6 As a result, traditional
receptors containing N–H groups, such as amide, sulfonamide,
urea, thiourea, and pyrrole, have been extensively employed.7
Recently, some new fashioned hydrogen bond donors, such as
squaramides and aliphatic polyols, have also been developed as
efficient anion receptors.8 It is worth mentioning that the studied
hydrogen bond sources of the aforementioned anion receptors
are mostly N–H groups. Relative fewer examples of the anion
receptors bearing phenolic hydroxyl groups were reported.9 In fact,
in nature, multiple hydrogen bonds using both N–H and O–H
donors were verified responsible for the anion recognition and
transport process.10 Therefore, designing a new kind of receptors,
especially cooperative with N–H and O–H functional groups, which
have great ability of recognizing biologically important anions, is
still a formidable challenge and highly desirable.
tert-Butanesulfinamide, which was developed by Ellman and
coworkers, has been widely used as a chiral auxiliary in asymmet-
ric synthesis.11 Recently, chiral sulfinamide based organocatalysts
have been reported for a series of important asymmetric transfor-
mations.12,13 However, unlike sulfonamides, sulfinamide based
O
S
O
S
O
S
Br
NO2
O
S
N
H
N
H
N
H
NH
HO
HO
HO
L1
L2
L3
O
S
O
S
O
S
NH
S
O
N
H
HO
N
H
N
H
O
OH
L713c
OH
⇑
Corresponding authors.
E-mail addresses: hxxywangb@mail.tjnu.edu.cn (B. Wang), xin_li@nankai.edu.cn
L4
L5
L6
(X. Li).
Scheme 1. Structure of the receptors.
y
These authors contribute the same to this work.
http://dx.doi.org/10.1016/j.tetlet.2015.12.090
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Shen, Y.-Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.090

2
Y.-Y. Shen et al. / Tetrahedron Letters xxx (2015) xxx–xxx
Figure 1. Stack plot of 1H NMR spectra (400 MHz, CDCl3) of receptor L1 (5 ꢁ 10ꢀ3 M) upon addition of Clꢀ ((Bu4N)Cl).
receptors have not been used in anion recognition. Herein, tert-
butanesulfinamide based phenols, which had been used as chiral
Lewis base catalysts in reduction of aromatic ketimines,13a were
chosen as cooperative body of N–H and O–H donors to examine
their anion recognition ability.
Table 1
Association constants (Ka(1:1)) of receptors with various anions in CDCl3
Clꢀ
NOꢀ3
AcOꢀ
44.3 2.1a
85.3 3.6a
697.5 37.1b
41.4 0.8a
65.9 6.8b
95.8 9.0b
<10
15.2 1.0a
78.3 4.8b
81.2 5.9a
18.0 1.3a
36.9 2.7b
40.0 2.4b
<10
47.2 2.1b
298.0 10.4b
—
Six target compounds (Scheme 1) were prepared from salicy-
laldehyde and tert-butanesulfinamide in two steps following the
reported procedures.13a Furthermore, disulfinyl compound L7,13d
which had double sulfinamide symmetrical structure, was also
prepared to investigate its anion binding ability (Scheme 1).
Initially, we investigated a range of potential guest anions by L1.
1H NMR experiment of a 1:1 mixture of L1 and several anions was
performed to examine the binding abilities. Since L1 showed poor
binding ability with the less basic anions (Brꢀ, Iꢀ), we mainly
tested the binding behavior of chlorine ion (Clꢀ), nitrate ion
L1
L2
L3
L4
L5
L6
L7
108.0 2.9b
184.2 10.0b
346.0 41.3b
<10
a
The association constants were determined by the chemical shift of proton of
phenolic hydroxyl.
The association constants were determined by the chemical shift of aromatic
proton.
b
Please cite this article in press as: Shen, Y.-Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.090

Y.-Y. Shen et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
Figure 2. Stack plot of 1H NMR spectra (400 MHz, CDCl3) of receptor L3 upon addition of AcOꢀ. Ratio of concentration [AcOꢀ]/[L3] is shown above.
(NOꢀ3 ), and acetate ion (AcOꢀ) in this work. As shown in Figure 1,
the O–H of L1 had an obvious downfield shift from 7.843 ppm to
9.605 ppm. This result indicated that the O–H had a strong interac-
tion with Clꢀ. Meanwhile, the aromatic proton of L1 at around
7 ppm had some shifts, which illustrated that the aromatic proton
also participated in Clꢀ binding. Unexpectedly, the proton of the
tert-butyl group at 1.262 ppm shifted upfield a little bit. It seemed
that the C–H of the tert-butyl group played a small role in the pro-
cess of anion recognition as a potential weak hydrogen bond donor.
All the evidences showed that L1 and Clꢀ had multiple hydrogen
bond interactions.
We then examined the titrations of other receptors (L2–L7)
and different anions (Clꢀ, NOꢀ3 and AcOꢀ). The binding affinity
was indicated by the changes of the chemical shifts of the proton
of the phenolic hydroxyl group or aromatic proton. And the bind-
ing affinity data are summarized in Table 1. All the titration
curves of receptors to anions give the best fit for the 1:1 binding
Figure 3. Optimized geometry of L3 and chloride complex in CHCl3 calculated with
the M06-2x/6-311+G(d,p) (SMD) method.
Please cite this article in press as: Shen, Y.-Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.090

4
Y.-Y. Shen et al. / Tetrahedron Letters xxx (2015) xxx–xxx
model in agreement with Job’s plot shown in the Supporting
information.
Acknowledgments
Among the examined three anions, NOꢀ3 showed the weakest
binding interactions with all the receptors. This maybe due to that
the basicity of NOꢀ3 is too weak. On the opposite, the AcOꢀ, which
had higher basicity, showed the strongest interactions with the
examined receptors. As for different receptors, L2 and L3, which
were substituted with electron withdrawing groups, they had
stronger binding affinity with all the three anions. As for receptor
L4, which substituted with a methoxy group, exhibited a slightly
stronger binding affinity than L1. Next, the effect of the different
position of the phenolic hydroxyl group on the anion recognition
was investigated. As shown in Table 1, the order of binding ability
of anion interaction was L6 > L5 > L1. The different hindrance
caused by the position of O–H, which affected the interaction
between the anion and the aromatic proton of receptors, was sus-
pected to induce the observed diversity of affinity data. It is note-
worthy that the interaction of L7 and anions, even with AcOꢀ, was
very weak, which could not get the binding affinity data via 1H
NMR titration. This fact illustrated that the hydroxyl group played
an important role in current studied anion interaction mode.
On careful examination of the experiment, we found that the
titration of the L3 and anions was a clear color change process,
in which the solution of the mixture of L3 and anions in CDCl3
changed from light yellow to deep yellow along with the increase
of the anion concentration. This interesting phenomenon indicated
that we can monitor the recognition of anion by L3 via a visual
observation.
The project was supported by 973 Program (2012CB821600),
NSFC (21390400, 21421062, 21172112 and 21172118) and the
‘‘111” project (B06005) of the Ministry of Education of China.
Supplementary data
Supplementary data (experimental procedures, analysis data of
new compounds, NMR spectra and titrations data) associated with
this article can be found, in the online version, at http://dx.doi.org/
10.1016/j.tetlet.2015.12.090.
References and notes
1. (a) Christianson, D. W.; Lipscomb, W. N. Acc. Chem. Res. 1989, 22, 62; (b) Berg, J.
M. Acc. Chem. Res. 1995, 28, 14.
2. (a) Gale, P. A.; Quesada, R. Coord. Chem. Rev. 2006, 250, 3219; (b) Steed, J. W.
Chem. Soc. Rev. 2009, 38, 506; (c) Yang, Z.-P.; Zhang, K.; Gong, F.-B.; Li, S.-Y.;
Chen, J.; Ma, J.-S.; Sobenina, L. N.; Mikhaleva, A. I.; Trofimov, B. A.; Yang, G. Q. J.
Photochem. Photobiol., A 2011, 217, 29; (d) Bao, X.-P.; Zhou, Y.-H. Sens. Actuators,
B 2010, 147, 434; (e) Evans, N.; Beer, H. P. D. Angew. Chem., Int. Ed. 2014, 53,
11716; (f) Busschaert, N.; Caltagirone, C.; Rossom, W. V.; Gale, P. A. Chem. Rev.
2015, 115, 8038.
3. (a) Zhang, Z.; Schreiner, P. R. Chem. Soc. Rev. 2009, 38, 1187; (b) Beckendorf, S.;
Asmus, S.; Mancheño, O. G. ChemCatChem 2012, 4, 926; (c) Brak, K.; Jacobsen, E.
N. Angew. Chem., Int. Ed. 2013, 52, 534; (d) Mahlau, M.; List, B. Angew. Chem., Int.
Ed. 2013, 52, 518; (e) Seidel, D. Synlett 2014, 783.
4. Gale, P. A.; Busschaert, N.; Haynes, C. J. E.; Karagiannidis, L. E.; Kirby, I. L. Chem.
Soc. Rev. 2014, 43, 205.
5. (a) Gale, P. A. Acc. Chem. Res. 2011, 44, 216; (b) Kruppa, M.; König, B. Chem. Rev.
2006, 106, 3520; (c) Giese, M.; Albrecht, M.; Rissanen, K. Chem. Rev. 2015, 115,
8867; (d) Liu, Y.-Z.; Yuan, K.; Lv, L.-L.; Zhu, Y.-C.; Yuan, Z. J. Phys. Chem. A 2015,
119, 5842; (e) Yuan, Z.; Liang, F. Curr. Org. Chem. 2014, 18, 2016.
As for the 1H NMR titration of AcOꢀ in L3, the chemical shift of
Ar–H appeared at 6.831 ppm and showed a significant downfield
shift upon the addition of AcOꢀ. However, the trend changed from
downfield shift into upfield shift accompanied with excessive addi-
tion of AcOꢀ. Simultaneously, the chemical shift of the proton of
AcOꢀ suddenly changed from 2.102 ppm to 2.025 ppm (Fig. 2),
which meant that the AcOꢀ had already become AcOH. UV–vis
experiment in CHCl3 was then conducted. During the titration of
L3 with Clꢀ, NOꢀ3 , and AcOꢀ by UV–vis, spectral change was
observed only upon addition of AcOꢀ. A new band at around
425 nm, which was the same as the absorbance band obtained
when strong base tetrabutylammonium hydroxide (TBAOH) was
added into L3, was observed. And from the UV–vis titration spectra
of L3 with AcOꢀ, we also found that the deprotonation happened at
the start of titration.14 The aforementioned evidences revealed a
fact that a typical Brønsted acid–base reaction should be happen
between L3 and AcOꢀ. Moreover, corresponding pKa values of
AcOH (12.6) and p-nitrophenol (10.8) can reasonably explain the
experimental observation.15
To further explore the interaction modes of the complex, the
geometry of the receptor L3 and chloride complex was optimized
with the M06-2X/6-311+G(d,p) (SMD) method.16,17 As illustrated
in Figure 3, the distances between the Clꢀ and the O–H proton
and the N–H proton are 2.015 and 2.323 Å, respectively. These dis-
tances are distinctly smaller than the sum (2.86–3 Å) of the van der
Waals radii of hydrogen and Clꢀ,18 thereby indicating the forma-
tion of hydrogen bond. It should be noted that the distance
between the Clꢀ and the C–H proton of the tert-butyl group is
3.420 Å. The distance is a little longer than the 3 Å, indicating the
possible weak interaction of C–Hꢂ ꢂ ꢂCl.
6. (a) Davis, A. P.; Joos, J.-B. Coord. Chem. Rev. 2003, 240, 143; (b) Li, F.; Gan, Q.;
Xue, L.; Wang, Z.-M.; Jiang, H. Tetrahedron Lett. 2009, 50, 2367.
7. For selected examples: (a) Klare, H.; Hanft, S.; Neudçrfl, J. M.; Schlçrer, N. E.;
Griesbeck, A.; Goldfuss, B. Chem. Eur. J. 2014, 20, 11847; (b) Amendola, V.;
Fabbrizzi, L.; Mosca, L. Chem. Soc. Rev. 2010, 39, 3889; (c) Hoque, M. N.; Gogoi,
A.; Das, G. Dalton Trans. 2015, 44, 15220; (d) Bernier, N.; Carvalho, S.; Li, F.;
Delgado, R.; Félix, V. J. Org. Chem. 2009, 74, 4819; (e) Pinter, T.; Jana, S.;
Courtemanche, R. J. M.; Hof, F. J. Org. Chem. 2011, 76, 3733; (f) Alliband, A.;
Meece, F. A.; Jayasinghe, C.; Burns, D. H. J. Org. Chem. 2013, 78, 356; (g) Ema, T.;
Okuda, K.; Watanabe, S.; Yamasaki, T.; Minami, T. Org. Lett. 2014, 16, 1302; (h)
Wienkers, M.; Ramos, J.; Jemal, H.; Cardenas, C.; Wiget, P.; Nelson, A.; Free, S.;
Wu, J.; Roach, R.; Vulcan, M.; Waynant, K.; Fort, K.; Vladimirova, A.; Sun, J.;
Hunt, S. E.; Rudkevich, D. M.; Starnes, S. D. Org. Lett. 2012, 14, 1370; (i) Ghule, N.
V.; Bhosale, S. V.; Bhosale, S. V. RSC Adv. 2014, 4, 27112.
8. (a) Edwards, S. J.; Valkenier, H.; Busschaert, N.; Gale, P. A.; Davis, A. P. Angew.
Chem., Int. Ed. 2015, 54, 4592; (b) Jin, C.; Zhang, M.; Wu, L.; Guan, Y.; Pan, Y.;
Jiang, J.; Lin, C.; Wang, L. Chem. Commun. 2013, 2025; (c) Elmes, R. B. P.; Yuen, K.
K. Y.; Jolliffe, K. A. Chem. Eur. J. 2014, 20, 7373; (d) Shokri, A.; Schmidt, J.; Wang,
X.-B.; Kass, S. R. J. Am. Chem. Soc. 2012, 134, 16944; (e) Gaeta, C.; Sala, C.; Sala, P.
D.; Margarucci, L.; Casapullo, A.; Neri, P. J. Org. Chem. 2014, 79, 3704; (f) Samet,
M.; Danesh-Yazdi, M.; Fattahi, A.; Kass, S. R. J. Org. Chem. 2015, 80, 1130; (g)
Martínez-Aguirre, M. A.; Yatsimirsky, A. K. J. Org. Chem. 2015, 80, 4985; (h)
Wang, X.; Feng, L.; Zhang, L. Sens. Actuators, B 2015, 208, 588; (i) Shokri, A.;
Wang, X.-B.; Kass, S. R. J. Am. Chem. Soc. 2013, 135, 9525.
9. (a) Wei, G.-N.; Zhang, J.-L.; Jia, C.; Fan, W.-Z.; Lin, L.-R. Spectrochim. Acta Part A
2014, 128, 168; (b) Sato, T.; Ito, K. J. Incl. Phenom. Macrocycl. Chem. 2013, 77,
385; (c) Staffilani, M.; Hancock, K. S. B.; Steed, J. W.; Holman, K. T.; Atwood, J. L.;
Juneja, R. K.; Burkhalter, R. S. J. Am. Chem. Soc. 1997, 119, 6324; (d) Fegade, U.;
Sahoo, S. K.; Singh, A.; Mahulikar, P.; Attarde, S.; Singh, N.; Kuwar, A. RSC Adv.
2014, 4, 15288; (e) Isaad, J.; Salaün, F. Sens. Actuators, B 2011, 157, 26; (f)
Schmidt, E. V. J.; Wang, X.-B.; Kass, S. R. J. Am. Chem. Soc. 2012, 134, 18534.
10. (a) Wang, Y.; Zhao, Q.; Zang, L.; Liang, C.; Jiang, S. Dyes Pigm. 2015, 123, 166; (b)
Yong, X.; Su, M.; Wan, W.; You, W.; Lu, X.; Qu, J.; Liu, R. New J. Chem. 2013, 37,
1591; (c) Stoikov, I. I.; Yantemirova, A. A.; Nosov, R. V.; Rizvanov, I. K.;
Julmetov, A. R.; Klochkov, V. V.; Antipin, I. S.; Konovalova, A. I.; Zharov, I. Org.
Biomol. Chem. 2011, 9, 3225; (d) Xu, L.; Li, Y.; Yu, Y.; Liu, T.; Cheng, S.; Liu, H.; Li,
Y.-L. Org. Biomol. Chem. 2012, 10, 4375; (e) Shokri, A.; Deng, S. H. M.; Wang, X.-
B.; Kass, S. R. Org. Chem. Front. 2014, 1, 54; (f) Guo, L.; Wang, Q.-L.; Jiang, Q.-Q.;
Jiang, Q.-J.; Jiang, Y.-B. J. Org. Chem. 2007, 72, 9947.
In summary, we have found that tert-butanesulfinamide based
phenols can act as receptors recognizing Clꢀ, NO3ꢀ, and AcOꢀ
through 1H NMR titration experiment. The information of the rela-
tionship between the structure of acceptors (or anions) and recog-
nition capability was discussed, which was helpful for the future
design of efficient tert-butanesulfinamide phenol type anion recep-
tors. To our knowledge, this is the first example of tert-butanesul-
finamide derived anion receptors.
11. (a) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997, 119, 9913; (b)
Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984; (c) Robak,
M. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600.
12. For highlight of chiral sulfinamides as organocatalysts, see: Diner, P.;
Sadhukhan, A.; Blomkvist, B. ChemCatChem 2014, 6, 3063.
13. (a) Pei, D.; Wang, Z.; Wei, S.; Zhang, Y.; Sun, J. Org. Lett. 2006, 8, 5913; (b)
Robak, M. T.; Trincado, M.; Ellman, J. A. J. Am. Chem. Soc. 2007, 129, 15110; (c)
Pei, D.; Zhang, Y.; Wei, S.-Y.; Wang, M.; Sun, J. Adv. Synth. Catal. 2008, 350, 619;
Please cite this article in press as: Shen, Y.-Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.090

Y.-Y. Shen et al. / Tetrahedron Letters xxx (2015) xxx–xxx
5
(d) Wang, C.; Wu, X.; Zhou, L.; Sun, J. Chem. Eur. J. 2008, 14, 8789; (e) Kimmel,
K. L.; Robak, M. T.; Ellman, J. A. J. Am. Chem. Soc. 2009, 131, 8754; (f) Xu, H.;
Zuend, S. J.; Woll, M. G.; Tao, Y.; Jacobsen, E. N. Science 2010, 327, 986; (g) Beck,
E. M.; Hyde, A. M.; Jacobsen, E. N. Org. Lett. 2011, 13, 4260; (h) Kimmel, K. L.;
Weaver, J. D.; Ellman, J. A. Chem. Sci. 2012, 3, 121; (i) Kimmel, K. L.; Weaver, J.
D.; Lee, M.; Ellman, J. A. J. Am. Chem. Soc. 2012, 134, 9058; (j) Saravanan, S.;
Khan, N.-U. H.; Kureshy, R. I.; Abdi, S. H. R.; Bajaj, H. C. ACS Catal. 2013, 3, 2873;
(k) Kumar, M.; Kureshy, R. I.; Saravanan, S.; Verma, S.; Jakhar, A.; Khan, N. H.;
Abdi, S. H. R.; Bajaj, H. C. Org. Lett. 2014, 16, 2798; (l) Wan, W.; Gao, W.; Ma, G.-
B.; Ma, L.; Wang, F.; Wang, J.; Jiang, H. Z.; Zhu, S.-Z.; Hao, J. RSC Adv. 2014, 4,
26563; (m) Wang, C.; Wu, X.-J.; Zhou, L.; Sun, J. Org. Biomol. Chem. 2015, 13,
577.
14. For details see the Supporting information.
15. Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456.
16. Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157.
17. Frisch, M. J. et al Gaussian 09, Revision B.01; Gaussian: Wallingford, CT, 2009.
18. Batsanov, S. S. Inorg. Mater. 2001, 37, 871.
Please cite this article in press as: Shen, Y.-Y.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.090