Cis alkenes stabilized by intramolecular sulphur?π interactions

Article abstract of DOI:10.1039/c9cc08558k

A series of alkenes with bistable isomers were obtained containing a thiophene/azoheteroaryl backbone. Visible light and heat-induced reversible cis ? trans isomerizations were evidenced by UV-Vis and ¹H NMR spectra. The stabilization of cis alkenes was attributed to intramolecular sulphur?π (S?π) interactions, which were further supported by theoretical calculations.

Full text of DOI:10.1039/c9cc08558k

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cis alkenes stabilized by intramolecular
sulphurꢀ ꢀ ꢀp interactions†
Cite this:DOI: 10.1039/c9cc08558k
ad
Xiaolei Zhao,ab Wei Zheng,a Yi Zhangc and Wei Huang
*
Received 2nd November 2019,
Accepted 9th December 2019
DOI: 10.1039/c9cc08558k
rsc.li/chemcomm
A series of alkenes with bistable isomers were obtained containing a undergo irreversible cyclization/oxidation of the cis isomer.7
thiophene/azoheteroaryl backbone. Visible light and heat-induced Thus, it seems necessary to develop an alkene that can easily
reversible cis " trans isomerizations were evidenced by UV-Vis and react photochromically, where both isomers are stable based on
1H NMR spectra. The stabilization of cis alkenes was attributed to trans/cis photoisomerization, so it can be used to functionalize
intramolecular sulphurꢀ ꢀ ꢀp (Sꢀ ꢀ ꢀp) interactions, which were further biological molecules with bistable molecular photoswitches.
supported by theoretical calculations.
A way to achieve this is through noncovalent interactions,8
which are ubiquitous in chemical and biological processes. In
Based on their tunable structure and properties, photo- addition to molecular stability,9 noncovalent interactions involving
isomerized molecules have attracted interest in various fields aromatic rings are increasingly finding applications in organic
including molecular memory, motors, manipulators, and solar synthesis to control the stereochemistry of transformations.10
thermal storage.1 To date, a number of molecular classes are known Moreover, the noncovalent forces are, in most instances, weaker
to undergo photoisomerization.2 Among them, azobenzenes are the than covalent bonds, and the molecular configurations supported
most extensively used photoswitches, namely for oligonucleotide by them are more easily converted. Recently, the nature of Sꢀꢀꢀp
modifications and biological applications, due to their ease of interactions has been explored in several studies.11 Compared to
synthesis, high quantum yield, and fast switching.3 However, a the well-accepted noncovalent interactions, (hydrogen-bonding,
serious intrinsic drawback of azobenzene is that electron-poor p–p stacking, and cation–p), most Sꢀꢀꢀp interactions are identified
azobenzenes may suffer from reduction under certain physiological and quantified in biological studies and less in chemical
conditions,4 which may limit their application in vivo.
Stilbenes are similar in structure to azobenzenes and exhibit realized, it is believed that it will have an important impact on the
similar photochemistry. They are interesting alternatives to configuration and properties of the resultant molecules.
systems.12 If the introduction of Sꢀꢀꢀp interactions in alkenes is
common azobenzenes, as stilbenes are not as sensitive to
To date, most sulfur atoms involved in Sꢀ ꢀ ꢀp interactions are
reduction.5 Nevertheless, differential thermal analysis shows commonly derived from thioethers and thiols,13 while other sulfur
that isomerization of stilbenes in the pure phase is not efficient sources are rarely reported. It is well known that thiophene is a
until the temperature reaches about 300 1C.6 The photoinduced better electron injection/transmission material because of its large
trans–cis isomerization in stilbenes is a slow process, even electron fluidity. This study describes the design of a novel
though the speed of the thermal back process is variable. The molecule that contains thiophene as the sulfur source and sub-
major disadvantage of using stilbenes is their tendency to stituted phenyl as the p surface. Herein, the synthesis of a series
of alkenes derived from 2-amino-4-chloro-5-formylthiophene-3-
carbonitrile has been reported (Scheme 1). It should be noted
that the desirable cis-3 and cis-4 can be produced by straight-
forward synthesis via the introduction of an electron-
withdrawing group to the phenyl group bonded to the alkene.
These cis isomers are distinguishable from traditional stilbenes
and azobenzenes wherein the thermally stable trans structures
are dominant.
Azo dyes 1a–1b were first prepared using standard diazo cou-
plings (Scheme S1, ESI†). Compounds 3–7 were then facilely pre-
pared between compounds 1a–1b and 4-substituted-benzyltriphenyl
a State Key Laboratory of Coordination Chemistry, School of Chemistry and
Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China.
E-mail: whuang@nju.edu.cn; Fax: +86 25 8968 2309; Tel: +86 25 8968 6526
b School of Chemical Engineering and Materials, Changzhou Institute of Technology,
Changzhou 213032, P. R. China
c Key Laboratory of Jiangxi Province for Professional Pollutants Control and
Resources, Nanchang Hangkong University, Nanchang 330063, P. R. China
d Shenzhen Research Institute of Nanjing University, Shenzhen, 518057, P. R. China
† Electronic supplementary information (ESI) available: Experimental and theo-
retical details. CCDC 1892457–1892461. For ESI and crystallographic data in CIF
or other electronic format, see DOI: 10.1039/c9cc08558k
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Scheme 1 Synthetic routes to compounds 3–7.
phosphonium salts (2a–2c) via Wittig reactions in modest
yields (Scheme 1). Our main considerations for using 1a and
1b as substrates are as follows: the adoption of a D–p–A azo unit
is to achieve longer wavelength absorption for the resulting
compounds and realize their isomerization via visible light.
Second, the cis–trans isomerization of the azo unit is difficult
even if irradiated with higher-energy light at 365 nm, which
could be ascribed to the absence of a strong UV-Vis p–p* band
in the range of 300–350 nm.11,14a,b So, the cis–trans isomeriza-
tion of the azo unit in our alkenes can be neglected. Analyses of
Fig. 1 ORTEP drawing (30% probability level) of cis-4 and cis-6 with the
atom-numbering scheme, together with the labelling of distances (Å)
between the centroids of the aryl rings and the sulfur atoms as well as
dihedral angles (1) between adjacent aromatic rings.
all products by 1H NMR spectroscopy (Fig. S4–S17, ESI†) ranging from 2.1(9) to 12.7(3)1. Remarkably, the phenyl ring (C)
disclose that alkenes 3–7 display different configurations, in cis-4 and cis-6 is torsional to the azoheteroaryl moiety, and
namely, compounds 5 and 6 exist as a mixture of cis and trans the related dihedral angles between the two adjacent aromatic
isomers in a ratio of 3 : 2. In contrast, compounds 3/4 and 7 are rings (B and C) at each side of the CQC bond vary from 63.5(7)1
only shown as either cis or trans isomers, respectively. The to 69.8(9)1 displaying cis configurations. In contrast, the dihedral
corresponding coupling constants (J) of the –CHQCH– units in angle in trans-7 is 13.0(3)1 and shows a general trans configu-
the 1H NMR spectra clearly verify the experimental results ration. In addition, the distance (d) between the centroids of
( J = 12.2 Hz for cis-3 and cis-4, J = 12.0, 16.1 Hz for cis-/trans- the corresponding aryl ring and sulfur atom is measured as
5 and cis-/trans-6 and J = 16.1 Hz for trans-7). This interesting 3.581(9) Å in cis-4 and 3.837(6) and 3.839(6) Å in cis-6. Compared
phenomenon originates from the substituents on the aromatic with the contact distance reported in the literature,14c it is
ring linked to the –CHQCH– units. The embedding of an inferred that an intramolecular Sꢀ ꢀ ꢀp interaction may favor the
electron-withdrawing group, –NO2, into the phenyl ring weak- twisted compound and it also works in the solution, thereby
ens the electron density of the acceptor, which contributes to possibly accessing the cis configuration of compounds 3, 4 and 6
additional access to more stable cis-3 and cis-4 isomers and vice both in the solid state and in CDCl3.
versa by implanting an electron-donating –CH3 group (trans-7).
Computational investigations were carried out to illustrate that
In a control experiment, a derivative without the azo unit intramolecular Sꢀꢀꢀp interactions have an important effect on
(compound trans-8 in Scheme S1, ESI†) was synthesized to alkene stabilization with cis configurations. As shown in Fig. 2,
compare with cis-3 and cis-4, where two doublets at d = 6.53 subtle interactions can be visualized for the computed conformer
and 7.33 ppm in the 1H NMR spectra (Fig. S19, ESI†) with of cis-4 and cis-6 using reduced density gradient (RDG) analysis,15
J = 16.1 Hz clearly verified its trans conformation. Thus, it is which was analyzed by the multiwfn software package.16a The
concluded that the presence of the delocalized azo system plays green areas between the sulfur atom and the benzene ring in the
a key role in maintaining the cis configuration for alkenes 3 and gradient isosurface figure indicate the existence of strong Sꢀꢀꢀp
4 with Sꢀ ꢀ ꢀp interactions.
interactions. The peaks at the sign(l2)r o 0 region in the plots of
X-ray single-crystal structures of cis-4 and cis-6, as well as RDG versus sign(l2)r (see Fig. S23, ESI†) also suggest attractive
trans-7, were obtained to provide additional insight into the Sꢀꢀꢀp interactions. Besides, atoms in molecules (AIMs) analysis16b
formation of the cis azoheteroaryl alkenes. As shown in Fig. 1 was performed to verify the presence of Sꢀ ꢀ ꢀp interactions.
(cis-4/cis-6) and Fig. S22 (trans-7 in the ESI†), the phenyl ring (A) Two bond critical points (BCP) were found in cis-4 and cis-6,
and the thiophene ring (B) linked to the NQN bond in all three respectively, and their corresponding electron densities r(r)
2
compounds are essentially coplanar with the dihedral angles and Laplacians of electron density r r(r) of BCPs are listed
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Fig. 3 (a) Visible light and heat-induced cis " trans isomerization of cis-
4. (b) Normalized UV-Vis spectra of photoisomerization from cis-4 to
trans-4 in CHCl3 upon irradiation at 570 nm and 25 1C with an interval of
20 min. (c) The reverse isomerization of trans-4 (red line) back to cis-4
(blue dotted line) triggered by heating under 60 1C for 1 h (full spectra can
be found in Fig. S25, ESI†).
Fig. 2 RDG surfaces: green areas indicate Sꢀ ꢀ ꢀp interactions for cis-4 (a)
and cis-6 (b).
in Table S3 (ESI†). Generally, electron densities r(r) represent
the strength of interactions.16c Accordingly, a larger r(r) at the
BCP in cis-4 implies that the Sꢀ ꢀ ꢀp interaction may be a little
stronger than that in cis-6, which may be affected by the 1 h (Fig. 3c and Fig. S24, S25, ESI†). Further tests of cis-4 in
substituted nitro group. Finally, electron density color-filled solution reveal an identical absorbance strength in its UV-Vis
maps for cis-4 and cis-6 have been displayed in Fig. S23 (ESI†). It spectrum lasting for at least 17 days (Fig. S26, ESI†), verifying
is obvious that a saddle point (identified by red stars) can be that the cis isomer is stable at room temperature. Based on the
found in each figure, which indicates the existence of BCP in experimental results, it is believed that both isomers of the
cis-4 and cis-6, thus further explaining the existence of intra- synthesized alkenes are stable and show promise as bistable
molecular Sꢀ ꢀ ꢀp interactions.
molecular switches.
Having prepared the cis configurational compounds, next,
Although the photoisomerization has been achieved for cis
evaluations of their photoisomerization behaviors depending alkenes, it is unclear whether the azo unit was involved in the
on their UV-Vis absorption spectra were studied (see the Note isomerization because of its sensibility to light. Hence, X-ray
in the ESI†). Varying N-substituted tails of cis alkenes 3–4 or single-crystal structures of trans-4 and trans-6 were collected by
cis/trans alkenes 5–6 linked to the benzene rings resulted in the corresponding photoisomerizations to further understand
almost identical spectral behavior.17 Therefore, UV-Vis spectro- the photoinduced changes in the molecular structure. As shown
scopy of representative cis-4 and cis-/trans-6 compounds was in Fig. S22 (ESI†), the phenyl ring (A) and the thiophene ring (B)
investigated to plot with the other alkenes. First, the UV-Vis linked to the NQN bond in the two compounds show perfect
spectra recorded the photoisomerization behaviors of cis-4 and planarity with the dihedral angles ranging from 3.7(1) to 9.3(5)1
cis-/trans-6 (Fig. 3 and Fig. S24, ESI†). As shown in Fig. 3b, cis-4 upon irradiation, indicating that the azo-groups in trans-4
shows a broad absorption maximum (lmax) at 582 nm (black and trans-6 do not drastically differ compared to the parent.
lines). Upon irradiation with 570 nm laser light at 25 1C, the However, the dihedral angles between the B and C rings fall
cis - trans isomerization gradually takes place leading to a new within the normal range of 5.3(6)–16.6(1)1 upon irradiation with
absorption band with lmax = 597 nm, which was also evidenced 570 nm light, manifesting that the –CQC– unit had been
by the presence of two isosbestic points at 335 and 425 nm. The converted to the trans isomer.
1
isomerization is accompanied by a slight color change of the
The aromatic region of the H NMR spectra of cis-4 before
solution from purple to blue. In contrast, cis-/trans-6 displays a and after irradiation in CDCl3 is displayed in Fig. S27 (ESI†).
similar bathochromic shift of 17 nm in the p–p* transition Comparing the spectra of the cis and trans isomers, the signals
band upon irradiation. The trans-6 isomer can be observed via for the cis isomer gradually vanish, whereas those corresponding
visible-light irradiation (lirr = 570 nm), as illustrated in Fig. S24 to the trans isomer progressively appear and increase with the
(ESI†), in which the adsorption peak at 565 nm for cis-/trans-6 increase in irradiation time. In particular, the chemical shifts of
disappears and a new absorption maximum (lmax = 582 nm) the alkene protons (H5 and H6) in trans-4 exhibit two doublets at
emerges after illumination for 1 h. This process was accom- d = 7.03 and 7.41 ppm that are located downfield relative to cis-4
panied by four isosbestic points at 264, 303, 341, and 384 nm with closer peaks at d = 6.79 and 6.86 ppm, indicating the
during the photoisomerization. It should also be noted that the successful isomerization induced by visible light. In addition,
photoisomerization process is reversible and the trans isomers the coupling constants of H5 and H6 vary from J = 12.2 Hz for
can be converted to the initial products by heating at 60 1C for cis-4 to 16.1 Hz for trans-4. Related characteristic regions of the
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1H NMR spectra of cis-/trans-6 in CDCl3 also indicate the
complete cis - trans conversion (Fig. S28, ESI†). As discussed
above, different from most alkene compounds, the initial cis
isomers are thermally stabilized in a preferential conformation
by the phenyl substituents and Sꢀ ꢀ ꢀp interactions, and they can
act as promising alkene-azoheteroaryl photoswitches in a wide
range of optical applications.
In summary, azoheteroaryl and substituted phenyl units
were implanted into each side of the –CHQCH– unit to build
a series of alkene-azoheteroaryl molecules, in which cis-3, cis-4,
cis-5/trans-5, cis-6/trans-6, and trans-7 alkenes could be gener-
ated by direct synthesis. It was seen that pure cis isomers 3 and
4 were stabilized by intramolecular Sꢀ ꢀ ꢀp interactions with the
assistance of synergistic substituents and D–p–A effects. It should
be noted that this kind of thiophene-based heteroaromatic struc-
ture involving Sꢀꢀꢀp interactions was not considered for alkene-
containing molecules prior to this research. Further reversible cis
" trans isomerization results suggest that cis- and trans isomers of
3–4 could act as potential bistable molecular switches. It is believed
that the current study opens a new way for tuning the conforma-
tions and photochromic switches of asymmetric alkenes.
M. Frigoli and G. H. Mehl, Org. Lett., 2010, 12, 4090–4093;
(h) J. Andreasson, U. Pischel, S. D. Straight, T. A. Moore, A. L.
Moore and D. Gust, J. Am. Chem. Soc., 2011, 133, 11641–11648;
(i) P. Lentes, E. Stadler, F. Rohricht, A. Brahms, J. Grobner,
F. D. Sonnichsen, G. Gescheidt and R. Herges, J. Am. Chem. Soc.,
2019, 141, 13592–13600; ( j) Z. W. Zhang, W. H. Wang, P. P. Jin,
J. D. Xue, L. Sun, J. H. Huang, J. J. Zhang and H. Tian, Nat. Commun.,
2019, 10, 4232.
3 (a) E. Merino, Chem. Soc. Rev., 2011, 40, 3835–3853; (b) Z. Mahimwalla,
K. G. Yager, J. Mamiya, A. Shishido, A. Priimagi and C. J. Barrett, Polym.
Bull., 2012, 69, 967–1006.
4 C. Boulegue, M. Loweneck, C. Renner and L. Moroder, ChemBioChem,
2007, 8, 591–594.
5 (a) M. Erdelyi, M. Varedian, C. Skold, I. B. Niklasson, J. Nurbo,
A. Persson, J. Bergquist and A. Gogoll, Org. Biomol. Chem., 2008, 6,
4356–4373; (b) M. Erdelyi, A. Karlen and A. Gogoll, Chem. – Eur. J.,
2006, 12, 403–412.
6 H. Meier, Angew. Chem., Int. Ed. Engl., 1992, 31, 1399–1420.
7 H. K. Cammenga, V. N. Emel’yanenko and S. P. Verevkin, Ind. Eng.
Chem. Res., 2009, 48, 10120–10128.
8 L. M. Salonen, M. Ellermann and F. Diederich, Angew. Chem., Int.
Ed., 2011, 50, 4808–4842.
9 (a) N. S. Scrutton and A. R. C. Raine, Biochem. J., 1996, 319, 1–8;
(b) S. C. R. Lummis, D. L. Beene, N. J. Harrison, H. A. Lester and
D. A. Dougherty, Chem. Biol., 2005, 12, 993–997; (c) X. Xiu,
N. L. Puskar, J. A. P. Shanata, H. A. Lester and D. A. Dougherty,
Nature, 2009, 458, 534–537; (d) J. Calbo, C. E. Weston, A. J. P. White,
H. S. Rzepa, J. Contreras-Garcia and M. J. Fuchter, J. Am. Chem. Soc.,
2017, 139, 1261–1274.
10 A. Bisai and V. K. Singh, Org. Lett., 2006, 8, 2405–2408.
11 C. Slavor, C. Yang, A. H. Heindl, H. A. Wegner, A. Dreuw and
J. Wachtveitl, Angew. Chem., Int. Ed., 2019, 58, 2–10.
12 (a) A. K. Lewis, K. M. Dunleavy, T. L. Senkow, C. Her, B. T. Horn,
M. A. Jersett, R. Mahling, M. R. McCarthy, G. T. Perell, C. C. Valley,
C. B. Karim, J. L. Gao, W. C. K. Pomerantz, D. D. Thomas,
A. Cembran, A. Hinderliter and J. N. Sachs, Nat. Chem. Biol., 2016,
12, 860–866; (b) B. R. Beno, K. S. Yeung, M. D. Bartberger,
L. D. Pennington and N. A. Meanwell, J. Med. Chem., 2015, 58,
4383–4438; (c) K. N. M. Daeffler, H. A. Lester and D. A. Dougherty,
J. Am. Chem. Soc., 2012, 134, 14890–14896; (d) L. M. Salonen,
M. Ellermann and F. Diederich, Angew. Chem., Int. Ed., 2011, 50,
4808–4842; (e) T. J. Mooibroek, P. Gamez and J. Reedijk, CrystEng-
Comm, 2008, 10, 1501–1515; ( f ) J. C. Aledo, F. R. Canton and
F. J. Veredas, Sci. Rep., 2015, 5, 16955.
13 (a) R. J. Zauhar, C. L. Colbert, R. S. Morgan and W. J. Welsh,
Biopolymers, 2000, 53, 233–248; (b) C. R. Forbes, S. K. Sinha,
H. K. Ganguly, S. Bai, G. P. A. Yap, S. Patel and N. J. Zondlo,
J. Am. Chem. Soc., 2017, 139, 1842–1855; (c) A. L. Ringer, A. Senenko
and C. D. Sherrill, Protein Sci., 2007, 16, 2216–2223; (d) T. P. Tauer,
M. E. Derrick and C. D. J. Sherrill, J. Phys. Chem. A, 2005, 109,
191–196.
This work was financially supported by the National Natural
Science Foundation of China (21871133 and 21601060), the
Natural Science Foundation of Jiangsu Province (BK20171334),
the Natural Science Foundation of the Jiangsu Higher Educa-
tion Institutions of China (19KJB150022), and the Science,
Technology and Innovation Commission of Shenzhen Munici-
pality (JCYJ20180307153251975).
Conflicts of interest
There are no conflicts to declare.
Notes and references
1 (a) R. Gostl, A. Senf and S. Hecht, Chem. Soc. Rev., 2014, 43,
1982–1996; (b) D. Bleger and S. Hecht, Angew. Chem., Int. Ed., 2015,
54, 11338–11349; (c) W. Szymanski, J. M. Beierle, H. A. V. Kistemaker,
W. A. Velema and B. L. Feringa, Chem. Rev., 2013, 113, 6114–6178;
(d) B. L. Feringa and W. R. Browne, Molecular Switches, VCH,
Weinheim, 2011; (e) M. M. Russew and S. Hecht, Adv. Mater., 2010,
22, 3348–3360; ( f ) T. J. Kucharski, N. Ferralis, A. M. Kolpak,
J. O. Zheng, D. G. Nocera and J. C. Grossman, Nat. Chem., 2014, 6,
441–447; (g) D. Zhitomirsky, E. Cho and J. C. Grossman, Adv. Energy
Mater., 2016, 6, 1502006; (h) Y. Feng, H. Liu, W. Luo, E. Liu, N. Zhao,
K. Yoshino and W. Feng, Sci. Rep., 2013, 3, 3260; (i) A. K. Saydjari,
P. Weis and S. Wu, Adv. Energy Mater., 2016, 1601622.
2 (a) Z. Y. Wang, E. K. Todd, X. S. Meng and J. P. Gao, J. Am. Chem.
Soc., 2005, 127, 11552–11553; (b) M. Kawamoto, T. Aoki and
T. Wada, Chem. Commun., 2007, 930–932; (c) M. C. Carreno,
I. Garcia, I. Nunez, I. Merino, M. Ribagorda, S. Pieraccini and
G. P. Spada, J. Am. Chem. Soc., 2007, 129, 7089–7100; (d) K. Takai-
shi, M. Kawamoto, K. Tsubaki and T. Wada, J. Org. Chem., 2009, 74,
5723–5726; (e) A. J. Myles, T. J. Wigglesworth and N. R. Branda, Adv.
Mater., 2003, 15, 745–748; ( f ) M. Frigoli and G. H. Mehl, Angew.
Chem., Int. Ed., 2005, 44, 5048–5052; (g) S. Delbaere, G. Vermeersch,
14 (a) C. E. Weston, R. D. Richardson, P. R. Haycock, A. J. P. White and
M. J. Fuchter, J. Am. Chem. Soc., 2014, 136, 11878–11881; (b) A. A. Beharry,
O. Sadovski and G. A. Woolley, J. Am. Chem. Soc., 2011, 133, 19684–19687;
(c) P. Chakrabarti and R. Bhattacharyya, Prog. Biophys. Mol. Biol., 2007, 95,
83–137.
´
´
15 (a) E. R. Johnson, S. Keinan, P. Mori-Sanchez, J. ContrerasGarcıa,
A. J. Cohen and W. Yang, J. Am. Chem. Soc., 2010, 132, 6498–6506;
´
(b) J. Contreras-Garcıa, E. R. Johnson, S. Keinan, R. Chaudret,
J.-P. Piquemal, D. N. Beratan and W. Yang, J. Chem. Theory Comput.,
2011, 7, 625–632.
16 (a) T. Lu and F. Chen, J. Comput. Chem., 2012, 33, 580–592; (b) R. F. W.
Bader, Chem. Rev., 1991, 91, 893–928; (c) L. Checinska, S. J. Grabowski
and M. Małecka, J. Phys. Org. Chem., 2003, 16, 213–219.
17 X. L. Zhao, J. Geng, H. F. Qian and W. Huang, Dyes Pigm., 2017, 147,
318–326.
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