Attraction or Repulsion? London Dispersion Forces Control Azobenzene Switches

Article abstract of DOI:10.1002/anie.201506126

Large substituents are commonly seen as entirely repulsive through steric hindrance. Such groups have additional attractive effects arising from weak London dispersion forces between the neutral atoms. Steric interactions are recognized to have a strong influence on isomerization processes, such as in azobenzene-based molecular switches. Textbooks indicate that steric hindrance destabilizes the Z isomers. Herein, we demonstrate that increasing the bulkiness of electronically equal substituents in the meta-position decreases the thermal reaction rates from the Z to the E isomers. DFT computations revealed that attractive dispersion forces essentially lower the energy of the Z isomers.

Full text of DOI:10.1002/anie.201506126

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Communications
International Edition: DOI: 10.1002/anie.201506126
German Edition: DOI: 10.1002/ange.201506126
Noncovalent Interactions
Attraction or Repulsion? London Dispersion Forces Control
Azobenzene Switches
Luca Schweighauser, Marcel A. Strauss, Silvia Bellotto, and Hermann A. Wegner*
Abstract: Large substituents are commonly seen as entirely
repulsive through steric hindrance. Such groups have addi-
tional attractive effects arising from weak London dispersion
forces between the neutral atoms. Steric interactions are
recognized to have a strong influence on isomerization
processes, such as in azobenzene-based molecular switches.
Textbooks indicate that steric hindrance destabilizes the
Z isomers. Herein, we demonstrate that increasing the bulki-
ness of electronically equal substituents in the meta-position
decreases the thermal reaction rates from the Z to the E
isomers. DFT computations revealed that attractive dispersion
forces essentially lower the energy of the Z isomers.
dynamically unstable Z to the stable E isomer.[16] Typically,
variations in the electronic nature of the substituents were
described. The incorporation of azo units into macrocyclic
structures has also been shown to influence the isomerization
properties.[17] In addition, integration into foldamers[18] and
polymers[19] were presented. Small intermolecular interac-
tions, such as van der Waals forces, are essential in the case of
solid-state switching.[20] Nonetheless, hardly any attention has
been given to the intramolecular effect of substitution with
electronically neutral substituents such as alkyl groups on
azobenzenes. The reason might be found in the well-accepted
conclusion that steric effects have a strong destabilizing
influence on the Z isomer.
E
very first-year chemistry student is taught that the larger an
At first glance this prediction is supported by the
observation of Rüchardt and co-workers, who investigated
the stability of aliphatic azo compounds by varying the size of
the alkyl substituents (Scheme 1a).[21] Increasing the bulki-
alkyl group is, the stronger is its steric repulsion. This concept
is the basis for rationalizing the higher stability of trans versus
cis isomers[1] as well as the higher stability of equatorial versus
axial substitutents in cyclohexanes.[2] Recent studies, however,
point out that attractive interactions were underestimated in
discussions on repulsive steric hindrance in chemistry.[3]
Namely, London dispersion interactions, which are part of
the van der Waals forces, were seen as extremely weak or
neutralized in solution.[4] Nonetheless, during the last few
years it was demonstrated that intramolecular London
dispersion forces have a strong impact, for example, on the
thermodynamic stability[5] and the conformation[6] of mole-
cules, on chemical reactions such as cycloadditions,[7] bio-
chemical processes,[8] as well as in coordination chemistry.[9] It
could be shown that London dispersion forces were respon-
sible for the stability of extremely sterically crowded mole-
[10]
À
cules with long C C bonds such as aryl ethanes
or
adamantyl dimers.[11]
An essential process in organic chemistry in which steric
interactions play an important role is the E$Z isomerization
of double bonds. Herein, the azobenzene scaffold has an
exceptional position, as it can be isomerized upon irradiation
with light.[12] Hence, it is not surprising that a wide range of
applications exploit the isomerization properties as a molec-
ular switch in areas ranging from material science[13] to bio-[14]
and medicinal chemistry.[15] The growing interest led to a large
increase in the number of publications on the effects of
substituents on the thermal isomerization from the thermo-
Scheme 1. a) Kinetic and thermodynamic data for the thermal Z to
E isomerization of two aliphatic azo compounds in mesitylene.
b) k values of two meta-substituted azobenzenes for the thermal Z to
E isomerization. c) The thermal Z to E isomerization of seven differ-
ently substituted azobenzenes investigated in this study (Ad=ada-
mantyl, Cy =cyclohexyl).
ness of the alkyl group leads to a decrease in the stability of
the corresponding Z isomer and to a faster thermal back
reaction to the E isomer. However, a comparison of known
literature k values for the thermal Z to E isomerization of
unsubstituted azobenzene 3[22] with 3,3’,5,5’-tetra-tert-butyl-
azobenzene (4)[16a] (Scheme 1b) shows the more crowded tert-
butyl-substituted derivative to be kinetically more stable.
To investigate this phenomenon seven differently substi-
tuted azobenzenes were prepared (Scheme 1c, for the syn-
thesis of azobenzenes 3–9 see the Supporting Information)
[*] L. Schweighauser, M. A. Strauss, Dr. S. Bellotto,
Prof. Dr. H. A. Wegner
Institut für Organische Chemie, Justus-Liebig-Universität Gießen
Heinrich-Buff-Ring 58, 35392 Gießen (Germany)
E-mail: hermann.a.wegner@org.chemie.uni-giessen.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201506126.
13436
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Figure 1. Half-lives of azobenzenes 3–9 measured in n-octane and
DMSO at 538C.
Figure 2. Experiment versus computation with a 6-311G(d,p) basis set
(558C).
and the rates of Z!E isomerization were determined by
temperature-controlled UV/Vis spectroscopy. In contrast to
the common opinion, the experimentally measured half-lives
at 538C in n-octane demonstrated that larger substituents
lower the reaction rates of the thermal Z to E transformation
dramatically (Figure 1). The unsubstituted azobenzene (3)
and the phenyl-substituted azobenzene (9) have a slightly
different electronic structure than the alkyl-substituted deriv-
atives. The isomerization was measured in different solvents
(6 ” 10À5 m n-octane and DMSO; chlorinated solvents were
adamantyl-substituted (8). Interestingly, the activation
enthalpy increases from Me to tBu substitution, but drops
again for adamantyl, while the entropy follows the opposite
trend. Solvation might be a dominant factor in this case.
A detailed mechanistic study was conducted to explain the
measured decrease in the reaction rates with increasing
bulkiness of substituents. For the herein-discussed electroni-
cally neutral azobenzenes, an inversion mechanism is com-
monly accepted.[16a,22] An isokinetic plot[24] (DH° versus DS°)
as well as an Exner plot[25] (log k398C versus log k678C
)
avoided to exclude protonation effects under irradiation[23]
)
supported this assumption and demonstrated that the mech-
anism is equal for all examples 3–9 (see the Supporting
Information).
and showed a comparable trend. The data determined on
samples at higher dilution (1 ” 10À5 m in both solvents)
resulted in the same trend (see Supporting Information),
thereby excluding the influence of intermolecular interac-
tions.
Measurements at temperatures between 398C and 678C
allowed the extraction of the DH°, DG°, and DS° values
(Table 1). The experimentally determined DG° values in n-
octane represent the measured half-lives, and increase as
expected from the methyl-substituted azobenzene (5) to
Further insights into the processes were gained by DFT
computations.[26] Attempts to reproduce the measured kinetic
trend at a B3LYP[27] level with a 6-311G(d,p)[28] basis set in the
gas phase were not successful (Figure 2). The computed DG°
and DH° values did not reflect the size of the substituent, but
resulted in the same values for all azobenzenes 3–9. Comput-
ing the kinetic values at the dispersion-corrected B3LYP-D3
level of Grimme et al.[29] allowed simulation of the exper-
imentally measured trend (Figure 2). The methyl-substituted
(5) displays the smallest and the adamantyl-substituted
azobenzene (8) the largest DG° value. The latter was
overestimated by the dispersion correction, probably as
a result of the missing solvation contributions and the large
number of possible interactions. In addition, the same out-
come was obtained when single-point computations were
conducted at a TPSSTPSS[30] level with a def2-TZVP[31] basis
set, thus eliminating functional-specific effects of B3LYP (see
the Supporting Information).
Geometry optimization of the tert-butyl derivative (4)
showed that the distance between the two closest hydrogen
atoms of two substituents on different benzene units is 2.37 Š
in the Z isomer, 4.33 Š in the transition state, and 6.24 Š in
the E isomer (Scheme 2). Hence, the dispersion effect should
mainly occur in the Z isomer, thereby explaining the kinetic
behavior of the thermal isomerization of azobenzene.
A noncovalent interaction analysis (NCI) was performed
to investigate the nature of the interactions occurring.[32]
Weak van der Waals forces are indicated with a green surface.
The outcome of the NCI analysis supported our previous
Table 1: Experimental kinetic data of the thermal Z!E isomerization of
3–9 in n-octane.
R
kZÀE
[sÀ1 [a]
DH°
DS°
DG°
Z-E
Z-E
Z-E
]
[kcalmolÀ1
]
[calKÀ1 molÀ1 [kcalmolÀ1 [b]
] ]
H
6.20”10À5 Æ4.72”
10À6
22.17Æ
0.22
À10.04Æ
0.68
25.46Æ0.44
25.04Æ0.33
26.34Æ0.39
26.50Æ0.20
Me
iPr
Cy
1.24”10À4 Æ1.23”
21.03Æ
À12.20Æ
10À5
0.17
0.51
1.62”10À5 Æ1.05”
10À6
22.99Æ
0.19
À10.20Æ
0.60
1.25”10À5 Æ5.13”
23.18Æ
À10.11Æ
10À7
0.10
0.30
tBu
Ad
Ph
7.18”10À6 Æ2.12”
10À7
24.15Æ
0.19
À8.26Æ0.59 26.86Æ0.39
À12.65Æ1.2 27.27Æ0.78
3.69”10À6 Æ1.01”
23.12Æ
10À7
0.39
2.81”10À5 Æ7.54”
10À7
22.21Æ
0.08
À11.49Æ
25.98Æ0.16
0.25
[a] At 538C. [b] At 558C.
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adamantyl derivatives (8), where the large size of the
substituents allowed weak attractive interactions to a small
extent in the transition states.
In conclusion, the rates of the thermal Z to E isomeriza-
tion of azobenzenes decrease as the bulkiness of the
substituents increase. We propose that the isomerization is
influenced by attractive London dispersion interactions
stabilizing the Z isomers. Although, the differences in the
activation enthalpies are small, they have a dramatic influ-
ence on the half-lives of the Z isomers. We could thus
demonstrate that electronically neutral and chemically inert
substituents can also influence the switching behavior of
azobenzenes. Even unsubstituted azobenzene is influenced by
attractive dispersion interactions, which illustrates that these
effects should be considered when investigating azo switches
and E to Z isomerizations in general. Further investigations
are directed at quantifying the stabilization energy for various
substituents, specifying the effects of entropy and different
solvents, as well as applying the concept to the design of novel
molecular switches.
Scheme 2. Geometry optimization of the Z and the E isomers and the
transition sate of the thermal isomerization of tert-butylazobenzene 4
[B3LYP-D3/6-311G(d,p)].
Acknowledgements
We thank Peter R. Schreiner, J. Philipp Wagner, Sebastian
Ahles, and Sçren Rçsel for useful discussions. We also thank
Heike Hausmann for NMR and Erwin Rçcker for MS
support. Manfred Schardt is kindly acknowledged for tech-
nical maintenance of the UV spectrometer.
Keywords: azobenzene · isomerization · London dispersion ·
molecular switches · steric interactions
Figure 3. NCI analysis of the optimized [B3LYP-D3/6-311G(d,p)]
Z isomers and transition states of tert-butyl derivative 4 (a) and
azobenzene 3 (b), visualized using VMD.[33]
How to cite: Angew. Chem. Int. Ed. 2015, 54, 13436–13439
Angew. Chem. 2015, 127, 13636–13639
assumptions: weak interactions were mainly detected in the
Z isomers and only to a minor extent in the transition states
(Figure 3a). Interestingly, dispersion forces also influence the
kinetics of the unsubstituted azobenzene (3; Figure 3b).
The computed dispersion-corrected data revealed that
stabilization of the Z isomers was the reason for the lower
reaction rates as the bulkiness increased, in accordance with
the Bell–Evans–Polanyi principle[21] (Table 2). The transition
state was hardly influenced by the different substitution
(DH°E-Z for the thermal conversion of 3–9 from the E to the
Z isomer is constant) even for the cyclohexyl (7) and
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Received: July 3, 2015
Published online: September 9, 2015
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