Arylazo-3,5-dimethylisoxazoles: Azoheteroarene Photoswitches Exhibiting High Z-Isomer Stability, Solid-State Photochromism, and Reversible Light-Induced Phase Transition

Article abstract of DOI:10.1002/chem.201902150

Reversibly photoswitchable phenylazo-3,5-dimethylisoxazole and 37 aryl-substituted derivatives were synthesized. Excellent photoswitching ability of these compounds in solution and the solid state was demonstrated. Through kinetics studies by means of NMR spectroscopy, high Z-isomer stability was demonstrated. Interestingly, the majority of the derivatives showed light-induced contrasting color changes in solution and the solid state. Besides, many of the derivatives exhibit partial phase transition upon UV irradiation. The highlight of this class of photoswitches is the reversible light-induced phase transition between solid and liquid phases in the parent compound, which can be used in patterned crystallization. These results show that this new class of azoheteroarene based photoswitches has opportunities to be useful in various domains.

Full text of DOI:10.1002/chem.201902150

A Journal of
Accepted Article
Title: Arylazo-3,5-dimethylisoxazoles – Azoheteroarene photoswitches
exhibiting high Z-isomer stability, solid state photochromism and
reversible light-induced phase transition
Authors: Sugumar Venkataramani, Pravesh Kumar, Anjali Srivastava,
Chitranjan Sah, and Sudha Devi
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To be cited as: Chem. Eur. J. 10.1002/chem.201902150
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10.1002/chem.201902150
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Arylazo-3,5-dimethylisoxazoles – Azoheteroarene photoswitches
exhibiting high Z-isomer stability, solid state photochromism and
reversible light-induced phase transition
Pravesh Kumar, Anjali Srivastava‡, Chitranjan Sah‡, Sudha Devi and Sugumar Venkataramani*
Dedicated to Prof. K. S. Viswanathan on the occasion of his retirement
azopyrazole was lowered by an order of two owing to steric
factors.[7b] Equally, the removal of N-methyl group of pyrazole
resulted in lowering of the half-life. Moreover, such systems with
3,5-dimethyl-NH-pyrazole derivatives were strongly susceptible
to substituent as well as hydrogen bonding effects. Substantial
influences of substituents have been predicted majorly through
the steric and electronic effects. However, the impact of
hydrogen-bonded dimerization at higher concentration, and
solvent-assisted tautomerism at lower concentration have also
been envisaged. This results in a complex interplay of all these
factors that influences the photoswitching and thermal reverse
isomerization steps. Either functionalization at pyrazole nitrogen,
or replacing N-H with a group or an atom that can disable the
hydrogen bond donating ability and tautomerism prospects could
be the viable strategies to overcome this situation. Since Fuchter
and coworkers already reported the benefits and improvement in
the half-life using N-Me group, the alternative strategy is still
unattempted. Accordingly, a simple replacement of N-H with O
to generate 3,5-dimethylisoxazole derivatives can open up yet
another class of photoswitches. Despite the fact that such
compounds have already been reported for their therapeutic
effects in medicinal chemistry, the photoswitching aspects have
been seldom studied.[11,12]
Abstract:
Reversibly
photoswitchable
phenylazo-3,5-
dimethylisoxazole and 37 aryl substituted derivatives have been
synthesized. Excellent photoswitching ability of these molecules in
solution and solid phase has been demonstrated. Through kinetics
studies using NMR spectroscopy, a long Z-isomer stability has also
been perceived. Interestingly, majority of the derivatives showed the
light-induced contrasting colour changes in solution as well as the
solid phase. Apart from that, many derivatives exhibit partial phase
transition upon UV light irradiation. The highlight of this class of
photoswitches is the reversible light-induced phase transition
between solid and liquid phases in the parent compound that can be
used in patterned crystallization. All these results on this new class
of azoheteroarene based photoswitches provide opportunities to be
useful in various domains.
Introduction
Azoheteroarenes are one of the increasingly popular classes of
photoswitches that acquired importance in various applications
such as spin-crossover, NIR dyes, catalysis, medicinal chemistry,
etc.[1-3] The replacement of aryl groups with heterocycles in the
azoarenes provides the possibility of coordination and the
hydrogen bonding networks.[4-5] Particularly, the presence of the
heterocyclic moiety closer to azo group significantly increases
the photoswitching properties and amplifies the application
potential. In this regard, azoimidazole[6], azopyrazoles[7] and
azoindoles[8] have been reported as the improved photoswitches
with excellent features such as increased Z-isomer stability,
The impact of the isoxazole moiety in photoswitching behavior
and thermal stability aspects of Z-isomers is the focus of this
contribution. Besides understanding those, the aryl substituent
effects and the added benefits of utilizing such photoswitches
were also considered. The advantage of isoxazole unit is that
hydrogen bonding and tautomeric channels are cut off, and so
steric and electronic influences of the substituents can be
realized. In this regard, we have synthesized arylazo-3,5-
dimethylisoxazole derivatives with different ortho, meta and para
substituents. A few selected di-substituted derivatives have also
been synthesized. Photoswitching studies have been carried out
for all the azo derivatives, and the analysis has been carried out
using UV-vis spectroscopy. The stability of the Z-isomer has
been estimated by following the first order thermal reverse
isomerization kinetics through NMR spectroscopy. In order to
determine the effects of substituents in electronic structural
aspects of both E- and Z-isomers, and also the stability aspects
undermining the reverse thermal isomerization, computations
have been extensively performed.
quantitative
isomerization
for
forward
and
reverse
photoisomerization steps, tunability, etc. Following this, many
other azoheteroarene classes and derivatives have also been
unraveled with interesting photophysical properties.[9] Among the
recently reported azoheteroarenes, Fuchter′s phenylazo-N-
methylpyrazole showed excellent photoswitching ability and Z-
isomer stability that enabled these systems to be utilized in
several applications.[10]
interactions was found to be a necessary condition in enhancing
the stability of the Z-isomer.
A
T-type geometry with C-H..
Interestingly, if methyl groups are introduced at the ortho
position to the azo group in the pyrazole moiety, the half-life of
During our investigations, apart from the photoswitching, we
have also observed photochromic behavior accompanied by the
light-induced phase transition in majority of the derivatives. The
native solid state of the molecules upon exposure to UV light
underwent partial to complete melting. Such room temperature
phase transitions provide a variety of applications such as
photolithography, reversible adhesives, photoresists, etc.[13]
Indeed, the parent phenylazo-3,5-dimethylisoxazole 1d is found
to be one of the simplest azo derivatives exhibiting such
reversible light-induced phase transition. For understanding this
phenomenon, differential scanning calorimetric (DSC), polarized
optical microscopic (POM) imaging, IR spectroscopic studies
[a]
Mr. P. Kumar, Ms. A. Srivastava, Mr. C. Sah, Ms. S. Devi, Dr. S.
Venkataramani
Department of Chemical Sciences
Indian Institute of Science Education and Research (IISER) Mohali
Sector 81, SAS Nagar, Knowledge City, Manauli – 140306, Punjab,
INDIA E-mail: sugumarv@iisermohali.ac.in
Equally contributed
‡
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201902150
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along with computations have also been carried out. Overall, the
investigations on arylazo-3,5-dimethylisoxazoles clearly reveal
that they are indeed a very interesting class of photoswitches
with several salient features. Herein, we report the details of the
synthesis, photoswitching, kinetics studies, and reversible light-
induced phase transition through spectroscopic and
arylazoisoxazole derivatives 1-37d (Figure 1, Table 1 and
Supporting Section S3). In this regard, the electronic spectral
analysis in a common solvent (acetonitrile) has been carried out
for all the derivatives. All the derivatives were subjected to 365
nm UV light irradiation in the same solvent to induce the E-Z
photoisomerization. In spite of the observation of changes in the
spectral features, the relative isomerization conversion was
found to vary from one derivative to the other. For few
derivatives such as 14d, 15d, 16d, 20d, 27d, 30d, 36d, and 37d,
exhibited poor isomerization conversion, inferred from the subtle
lowering of intensity without a significant blue shift, a key
signature for the −* transition corresponding to E-Z
isomerization process. However, we observed an enhancement
in the n−* feature indicating the isomerization. Apart from that,
the presence of isosbestic points confirmed the interconversion
between the two isomers without any intermediate. On the other
hand, excellent photoswitching has been observed in many
derivatives based on both the variation in the intensity as well as
the blue shifts at the −* band.
computational
photoswitches.
studies
on
arylazo-3,5-dimethylisoxazole
Results and Discussion
Synthesis:
adopted
A
in
common diazonium salt strategy has been
synthesizing the parent phenylazo-3,5-
dimethylisoxazole and majority of their 36 substituted derivatives
(Scheme and Supporting Section S2). In this regard,
1
commercially available aniline derivatives have been used as
the starting materials. Both the generation of hydrazone
derivatives 1-37c, and the consecutive cyclization step with
hydroxylamine hydrochloride to access the target isoxazole
based derivatives 1-37d have been adopted using the literature
procedure.[7c] However, the presence of a base provided good to
excellent yields in the cyclization step. The 2-amino derivative
32d was synthesized by reduction of the corresponding nitro
derivative 20d.[14] On the other hand, 3- and 4-amino derivatives
33d and 34d were obtained through the hydrolysis of 23d and
24d, respectively.
For a better understanding of the substituent effects on the E-
and Z-isomers, the electronic spectral characteristics have been
utilized in the form of max vs  plots (Figure 2). At the outset,
both the −* and n−* absorption features in E- and Z-isomers
of all the compounds have been modeled around the parent 1d
using this  vs max plot. The plots have been split into four
quadrants by keeping the corresponding max and  values of the
parent compound 1d as the origin. The results revealed that
both the −* and n−* absorption maxima were more sensitive
to the substituents in the Z- than in the E-isomers. In general,
the para-substitution influences the max, whereas the meta- and
ortho-substituents affects the molar absorptivity of the −*
absorptions in both E- and Z-isomers. This observation can be
due to the interplay of electronic effects through inductive and
mesomeric effects. Indeed, the role of steric effect can clearly be
understood from the shifts in 2-substituted analogs, where n−*
bands were found to be more susceptible.
Entry
1d
2d
3d
4d
5d
6d
7d
8d
R =
Nil
2-F
3-F
4-F
2-Cl
3-Cl
4-Cl
2-Br
Yieldd
85
96
89
50
54
84
85
67
72
75
94
93
71
79
89
62
78
75
80
Entry
20d
21d
22d
23d
24d
25d
26d
27d
28d
29d
30d
31d
32de
33df
34df
35d
36d
37d
R =
2-NO2
4-NO2
Yieldd
60
97
87
82
80
78
54
71
78
54
53
87
78
82
73
51
78
69
4-CH3
3-NHCOCH3
4-NHCOCH3
R-Ph = α-Naphthyl
2,5, di-Cl
2,6-di-Cl
9d
3-Br
4-Br
4-I
2,4-di-F
2,5-di-F
2,6-di-F
3,5-di-F
2-NH2
3-NH2
4-NH2
2-CN
10d
11d
12d
13d
14d
15d
16d
17d
18d
19d
2-OH
3-OH
4-OH
3-CF3
4-CF3
2-OCH3
3-O CH3
4-O CH3
R-Ph = 3-Pyridyl
R-Ph = 4-(Ph-N=N-Ph)
Scheme 1. Synthesis of substituted phenylazoisoxazole derivatives 1-37d.
Conditions: (a) NaNO2, HCl, H2O, 0-5 oC; (b) acac, NaOAc; (c) NH2OH.HCl,
Na2CO3, EtOH, reflux; (d) isolated yields of the final step; (e) Condition: 20d,
Na2S.9H2O, 1,4-dioxane, EtOH, H2O, reflux; (f) Condition: 23d/24d, conc. HCl,
EtOH, reflux.
Absorption properties and photoswitching in solution
phase and solid-state: In order to understand the effects of
substituents and also to evaluate their impact on photoswitching
characteristics, we have compared the electronic spectral
properties of the native E- and Z-isomers of all the 37
Figure 1. Photoisomerization in phenylazo-3,5-dimethylisoxazole 1d. Analysis
of reversible E-Z photoisomerization in 1d using UV-Vis spectroscopy in (a)
solution phase (Solvent: CH3CN, 35.8 M); (b) in solid phase (Medium: KBr);
Analysis of photoswitching using 1H-NMR spectroscopy (Solvent: CDCl3, 9.9
mM); (c) Before irradiation; (d) After 365 nm irradiation; (e) After 505 nm
irradiation;
(f)
Reversible
photoisomerization
in
1d.
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Table 1. UV-Vis spectroscopic and photoswitching data of (E)- and (Z)- isomers of phenylazo-3,5-
dimethylisoxazole derivatives 1-37d.
E-isomera
Z-isomera
R=
E-Z
PSSb
(%Z)
Z-E
−
n−
−
n−
max, 
trans
cis
PSSc
(%E)

max, 

max, 

max, 
315
(18162±117)
422
(481±17)
46
59
302
(15100)
428
(1428)
78
76
1
1d
2d
H
2-F
107
95
126
109
119
132
122
135
135
118
123
137
137
316
144
-
13
8
36
42
56
37
51
39
28
56
41
32
28
39
36
48
34
62
64
46
28
35
28
41
33
27
70
50
60
321
(14301±183)
416
(609±7)
313
(16782)
422
(1345)
2
47
34
76
93
315
(8340±753)
421
(336±36)
309
(7741)
428
(916)
3
3d
3-F
106
103
103
110
100
107
108
96
6
318
(16360±153)
421
(481±8)
93
80
296
(6857)
428
(1378)
80
82
4
4d
4-F
22
17
21
29
11
9
321
(12124±220)
424
(383±40)
304
(8889)
426
(1186)
5
5d
2-Cl
58
66
75
81
315
(17731±71)
425
(425±15)
294
(6181)
429
(1605)
6
6d
3-Cl
323
(22789±269)
423
(670±16)
92
94
294
(7780)
429
(2301)
78
62
7
7d
4-Cl
321
(9830±688)
428
(418±7)
310
(15503)
428
(1112)
8
8d
2-Br
42
81
315
(7822±744)
423
(388±35)
91
89
306
(11094)
429
(1750)
84
76
9
9d
3-Br
325
(21083±89)
421
(679±14)
295
(13767)
432
(1976)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
10d
11d
12d
13d
14d
15d
16d
17d
18d
19d
20d
21d
22d
23d
24d
25d
26d
27d
4-Br
49
67
46
84
73
73
30
35
-
330
(23665±614)
424
(830±35)
295
(11728)
432
(4530)
4-I
94
316
(17128±549)
316
(20660)
2-OH
3-OH
4-OH
3-CF3
4-CF3
2-OMe
3-OMe
4-OMe
2-NO2
4-NO2
4-CH3
3-NHAc
4-NHAc
-
-
-
313
(16908±46)
418
(596±15)
67
87
288
(8317)
432
(1948)
76
80
105
-
25
-
340
-
-
-
-
-
314
(19730±419)
418
(569±54)
308
(32445)
426
(1081)
104
113
103
111
66
38
35
62
68
118
120
141
141
125
97
77
83
69
75
6
312
(8744±757)
425
(384±8)
309
(20332)
429
(817)
3
311
(10598±419)
414
(1036±36)
285
(6732)
426
(2296)
26
23
28
-
312
(14802±133)
423
(604±16)
289
(7002)
430
(1813)
337
(21570±319)
403
(1314±138)
65
98
309
(20332)
434
(3187)
82
92
318
(17241±110)
421
(640±19)
318
(91429)
415
(1037)
103
99
16
55
42
69
65
59
53
23
92
86
93
69
35
79
85
82
332
(22095±113)
431
(905±30)
295
(18140)
436
(2393)
141
122
134
122
98
37
15
20
27
20
22
5
323
(12333±1450)
420
(973±34)
308
(23450)
430
(2220)
97
315
(18797±1328)
429
(573±48)
295
(8842)
429
(2171)
114
74
342
(25152±129)
416
(1336±28)
315
(14035)
437
(8817)
R-Ph = α-
362
(6789±354)
439
(881±10)
342
(4876)
440
(1970)
77
Np
320
(10850±556)
430
(452±16)
298
(10045)
427
(1267)
2,5-diCl
2,6-diCl
110
132
129
129
297
(10893±31)
429
(409±8)
292
(36409)
421
(809)
420
324
(20900±443)
420
(766±53)
323
(27197)
28
28d
2,4-diF
96
44
(1818)
97
72
1
36
328
(16027±77)
417
(583±12)
287
(8405)
422
(2222)
29
30
29d
30d
2,5-diF
2,6-diF
89
68
30
135
114
70
73
41
4
38
38
309
(16809±155)
419
(882±28)
305
(26476)
419
(1646)
110
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315
(16104±19)
417
(427±10)
297
(10953)
429
(1324)
31
32
33
34
35
36
31d
32d
33d
34d
35d
36d
3,5-diF
2-NH2
3-NH2
4-NH2
2-CN
102
-
60
132
134
138
91
82
18
6
36
34
36
38
52
83
310
(11667±1227)
54
61
304
(14387)
438
(7566)
60
92
-
315
(18293±113)
373
(3212±14)
290
(9804)
428
(2590)
58
-
65
53
73
70
25
23
21
5
371
(17176±378)
348
(15207)
439
(4988)
-
325
(16353±1035)
431
(499±39)
65
90
304
(8317)
434
(1501)
78
83
106
105
130
118
R-Ph = 3-
Pyridine
316
(7810±1340)
421
(376±7)
311
(40431)
429
(741)
18
98
R-Ph = 4-
(Ph-N=N-
Ph)
358
(37483±309)
428
(3041±60)
348
(65006)
434
(4051)
37
37d
70
37
86
87
10
17
aThe values of max are given in nm and  in L.mol-1.cm-1; bPSS for E-Z isomerization has been estimated at 365 nm (normal: UV-Vis (CH3CN); bold: 1H-NMR
(italics: CDCl3 (1d & 32d); normal: DMSO-d6); cPSS for Z-E isomerization has been estimated at appropriate wavelengths of light as indicated in the supporting
Table S2 with 2-5% uncertainity7a (normal: UV-Vis (CH3CN); bold: 1H-NMR (italics: CDCl3 (1d & 32d); normal: DMSO-d6); dThe difference in the −* absorptions
for E- and Z-isomers has been estimated in understanding the degree of conjugation breaking upon isomerization. (The  values for Z-isomers have been
estimated based on the PSS composition at E-Z isomerization step; α-Np = α-naphthyl.)
Figure 2. Effect of substituents in the absorption properties of E- and Z-isomers of the substituted phenylazo-3,5-dimethylisoxazoles: (a) and (b) corresponding to
−* and n−* absorptions for E-isomers, respectively; (c) and (d) corresponding to −* and n−* absorptions for Z-isomers, respectively. (The variation in the
absorption in terms of  and max shifts are separated into four quadrants with respect to that of the parent 1d, which was considered as the origin.)
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The solution phase photoswitching showed only a minimal
concentration dependency in the forward isomerization step.
angles, charges at the azo nitrogens) with respect to their parent
E- and Z-isomers have been closely inspected. In spite of
significant changes in those parameters, the computed structural
data did not show any trend that can be accountable for the
electronic effects of the substituents. In fact, this observation
was also seen in the case of arylazopyrazoles with meta-
substitution.[7c] Likewise, in our earlier studies on
arylazopyrazoles, the inspection of molecular orbitals
corresponds to HOMO-1, HOMO and LUMO of the E-isomer of
phenylazoisoxazole revealed the n-, - and *-orbitals,
respectively. On the other hand, the Z-isomer showed a mix of n
and  character in the HOMO-1 and HOMO orbitals, whereas,
the LUMO was found to be *-orbital (Supporting Figure SC1).
The energy gaps corresponding to n-* and -* MOs exhibited
minimal changes with respect to substituents. These computed
results have already been observed experimentally, where the
meta-substituted derivatives showed only perturbation in the 
values rather than max. The only exception was the meta
substitution with methoxy group, where the energy gap was
found to be marginally higher. Interestingly, for the
corresponding Z-isomers, more variation in the n-* energy gap
was observed, whereas only subtle changes were observed in
the case of −* energy gaps. These changes in the n-* energy
gap can be attributed to the mixing of n and  character in
Even at
a very high concentration (1.6 mM), the E-Z
isomerization was found to be as good as at M concentration
(supporting Figure S1). This clearly supported our understanding
(based on the earlier studies on azopyrazoles) that the
photoisomerization step can be limited by the hydrogen
bonding.7c Surprisingly, the 2-hydroxy 12d and 2-amino 32d
substituted derivatives were also found to undergo
photoswitching. This is in contrary to many azoarenes and
azoheteroarenes with such functional groups at ortho position,
which has been attributed to the intramolecular hydrogen
bonding and the resulting tautomeric equilibrium.[15] However, at
higher concentration, 12d did not show any photoswitching
indicating that either the reverse isomerization step is faster or
intermolecular hydrogen bonding dominates. Compared to the
hydroxy, the amino derivative indeed showed
photoswitching. Indeed, 32d exhibited visible
a
better
light
photoswitching as well. For obtaining better prospects, both the
molecules were subjected to photoswitching and were followed
by NMR spectroscopy as well. The 1H-NMR of the hydroxy
protons in 12d was found to appear at 11.94 ppm, clearly
indicating the possibility of an intramolecular hydrogen bonding
with the azo nitrogen. On the other hand, the amine protons in
32d were not strongly influenced by the hydrogen bonding
inferred from the appearance of a single broad signal around
5.35 ppm. In yet another case of bis(azo) derivative 37d, we
observed photoswitching, in which four different species were
observed, due to the unsymmetrical environment about the two
azo groups. Since the photoisomerization happens only to a
limited extent, both forward and the reverse isomerization steps
led to a mixture of photoproducts. For the best photoswitching
derivatives, PSS compositions have been estimated using 1H-
NMR that revealed good to excellent photoswitching for both
forward and reverse isomerization steps (Supporting Section S6).
Furthermore, the studies on selected derivatives by repeating
the forward and reverse photoswitching over five cycles using
UV-vis spectroscopy revealed the photoswitching stability
without any fatigue (Supporting Section S7).
HOMO-1, and subsequent accumulation of substantial

character leading to the electronic effects.
Apart from the solution phase photoisomerization, all the 37
arylazoisoxazole derivatives have been subjected to solid-state
photoswitching. In this regard, we have studied the reversible
photoisomerization of them in KBr medium. Despite showing
excellent E-Z photoisomerization, the reverse step was found to
be partial in the majority of the derivatives. In order to
understand the efficiency of the photoisomerization, the
isomerization conversion has been estimated at their respective
photostationary states (PSS) for the forward E-Z and reverse Z-
E step in the solid-state, as well as in the solution phase. The
PSS compositions have been estimated based on the literature
methods[4a,7a,7c,10c] and the results are tabulated (Table 1 and
Supporting Table S2 for solid-state PSS data).
Computational studies[16]: For understanding the effects of the
substituents in the electronic structure of the E- and Z-isomers of
the arylazo-3,5-dimethylisoxazoles, selected meta-substituted
derivatives have been chosen.[17] In order to envisage the effects
of substituents on structural characteristics, various properties
such as geometries, MOs, and the isomerization mechanisms
have been considered and computed at B3LYP/6-311G(d,p) and
M06-2X/6-311G(d,p) levels of theory. Primarily, we optimized
Figure 3. (a) First order reverse thermal (Z-E) isomerization kinetics of
phenylazo-3,5-dimethylisoxazole at 80 ± 2 oC. (Solvent: DMSO-d6; 9.9 mM) (b)
Thermal Z-E isomerization channels in phenylazo-3,5-dimethylisoxazole 1d for
two different conformations. (The energies are given in kcal/mol; Normal –
B3LYP/6-311G(d,p) and Italics – M06-2X/6-311G(d,p)) The TS1 and TS2
correspond to the inversion mechanism, whereas the TS3 is maxima in the
rotational channel.
the
E-
and
Z-isomers
of
the
selected
arylazo-3,5-dimethylisoxazoles derivatives to their minima and
their thermochemistry data has been obtained (supporting
Tables SC1-16). Essentially, the geometrical features (dihedral
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Thermal stability of Z-isomers: Apart from the efficient
photoswitching in the forward E-Z and the reverse Z-E
isomerization steps, the stability of the Z-isomer is a decisive
factor in many practical applications. So often the thermal
reverse isomerization is a crucial step in influencing the utility. In
this regard, we have utilized the NMR spectroscopy.[18] The
room temperature (25 ± 2 oC) kinetics showed a slow rate of
isomerization with a half-life of 45.5 days in DMSO-d6. On the
other hand, the half-lives have been estimated to be 111, 48 and
16 min, if the kinetics have been followed at 70 ± 2, 80 ± 2 and
90 ± 2 oC, respectively (Figure 3a and Supporting Figure S4).[19a]
Using these variable temperature kinetics data, the activation
parameters for the reverse thermal isomerization step have
been estimated (Supporting Figure S6). The activation barrier for
the reaction in 1d was found to be 116 ± 3 kJ.mol-1, which is
comparable with few of the thermally long-lived Z-isomers of the
azoarene and azoheteroarenes known.[7a,19b,20]
a trend with a positive slope despite the poor correlation, which
showed
agreement
with
our
previous
studies
on
arylazopyrazoles and arylazo-N-methylpyrazoles (Supporting
Figure SC2). Thus, the arylazo-3,5-dimethylisoxazoles exhibit
substantial electronic effects in the thermal stability of Z-isomers,
without the influence of the hydrogen bonding.
Inversion and rotational transition states were reported to be the
major mechanistic channels for the thermal Z-E isomerization in
many azoheteroarenes. Depending on the heterocycles, the
pathway can vary, which necessitates the investigation on the
mechanistic aspects.[7b,7c,8] In this regard, we have computed
both the mechanistic channels in the Z-E isomerization
pathways
of
arylazo-3,5-dimethylisoxazole.
Due
to
unsymmetrical substituents about the azo group in
arylazoisoxazoles, there can be two inversion pathways
(inversion along isoxazole ring or along phenyl ring).
Furthermore, the conformations of the isoxazole ring relative to
the azo group (N-O and O-N) can potentially lead to additional
inversion channels.[21a] On the other hand, the rotational barrier
can only be influenced by the conformational preference of the
isoxazole ring relative to the azo group and so only two different
transition states are possible. All the possible channels have
been computed at B3LYP/6-311G(d,p) and M06-2X/6-311G(d,p)
and are indicated in figure 3b.[21b] During our investigations, the
thermal barrier for inversion along phenyl ring was found to be
the lowest channel among all possible barriers in both the levels
of theory.[21c] This is consistent with similar systems such as
arylazopyrazoles and arylazoimidazoles.[7b,7c,6b] Indeed, the
rotational channels were found to have a barrier more than two
times of the minimal energy inversion pathway.
Figure 4. Light-induced phase transition in phenylazo-3,5-dimethylisoxazole.
POM image of 1d (a) before UV irradiation (b) after 30 s of irradiation at 365
nm light (rt); DSC curves obtained (c) before irradiation and (d) after irradiation
at 365 nm light. (Heating rate: 10 oC/min) (e) diagram showing the application
of photomelting in molding
a desired crystalline shape; (f) Photographic
images depicting the photomelting under UV light, and patterning the molten
sample; (g and h) in the mid-way and at the end of the crystallization under
white light irradiation (CFL bulb), respectively.
Light-induced phase transition: One of the salient features of
the arylazoisoxazole derivatives is the light-induced phase
transition. Many of the derivatives exhibited minimal to partial
melting upon solid state irradiation at the UV light (365 nm)
Since the arylazoisoxazole derivatives exhibited long half-life for
Z-isomers, the thermal reverse isomerization rate constants
have not been studied experimentally for all the isomers. Instead, accompanied by contrasting color changes. Remarkably, the
the influence of the electronic effect on the thermal barriers has
been computationally studied. For consistency with our previous
work, we have considered only the derivatives with meta
substitution. For all these derivatives, we have estimated the
inversion barriers. In all the cases, the transition state acquired a
twisted geometry for the inversion along the isoxazole ring
whereas, it attained T-shaped geometry for the inversion along
the phenyl ring. In principle, we considered both the transition
states and obtained weighted average barriers in the estimation
of rate constants. Hammett relationships for meta-substituted
phenylazo-3,5-dimethyl isoxazole using rate constants revealed
parent compound 1d showed complete melting. For obtaining
further insights, we have followed this phenomenon using POM.
The phase transition was observed as changes in the
birefringence pattern that gradually turned into a dark, as a
result of the conversion of crystalline (E)-1d into an isotropic
molten phase upon irradiation at 365 nm (Figure 4). As expected,
the DSC studies revealed a clear difference in the phase
transition behavior for both the E-isomer and the molten sample.
The native sample of 1d exhibited both solid to liquid phase
transition on heating as well as the liquid to solid phase
transition upon cooling. Indeed, the molten sample did not
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change its phase even after cooling to -60 oC. In order to
understand whether the heating effect of the light source
induces the melting, aliquot of sample was kept under water and
irradiated. Still, we observed the melting phenomenon.[22]
based photoswitches. The ease of synthesis, high yields,
excellent photoswitching in solution phase and long half-life of Z-
isomer make them robust photoswitchable systems. Based on
the extensive photoswitching studies, we found out that the
parent 1d, 4-fluoro 4d, 3-bromo 9d, and 4-methoxy 19d
derivatives were found to be the best photoswitches among the
37 derivatives. On the other hand, most of the other derivatives
exhibited moderate to good photoswitching. The photoswitching
stability studies on the better photoswitching candidates
revealed no fatigue over five cycles. The reverse thermal
isomerization kinetics revealed a long half-life for Z-isomers.
Besides that, these molecules showed photoswitching in solid-
state as well. Most importantly, the parent compound 1d was
found to exhibit a reversible light-induced phase transition with
contrasting colors that can potentially be useful in patterned
crystallization. All these salient features make them ideal for
many applications.
1
Furthermore, IR spectroscopic studies and inspection of the H-
NMR of the molten sample, and we observed a small amount of
Z-isomer (Supporting sections S11 and S12).[23,24] Presumably,
the presence of Z-isomer and long thermal stability of it prevents
the freezing of the molten sample. On the other hand, irradiation
of the molten sample using white light led to the change in the
phase as well as induce crystallization. Interestingly, the color
changes were prominent during this reverse step. An initial
orange colored crystalline phase started to appear that
ultimately led to a yellow colored crystalline phase. Through the
white light irradiation, we were able to crystallize the sample in
two hours, whereas, the crystallization was found to be at an
extremely slower rate if the same sample was kept at RT that
took few days. By using this reversible light-induced phase
transition, we were able to demonstrate
a
patterned
crystallization of the 1d (Figure 4e-h).
Acknowledgements
In order to shed light on this phase transition phenomenon, we
considered the crystal structure of 1d, and computational data
on the possible dimers of 1d, and accompanying changes in the
non-covalent interactions upon isomerization (Supporting
sections S15 and S16). Based on the XRD data, the packing
was mainly held by several cooperative weak contacts such as
− interactions, N…H-C, and azo-N with the aryl rings.
Presumably, the absence of strong intermolecular interactions,
provides the necessary conditions for phase transition upon
irradiation in 1d. Computationally, we also attempted at
optimizing the possible dimeric structures based on the crystal
packing at B3LYP/6-311G(d,p) and M06-2X/6-311G(d,p) levels
of theory. Through these, we were able to optimize the dimeric
structure relevant to − interactions of the phenyl and isoxazole
rings. Whereas, the other possible structure with head to head
interactions led to disorientation. On the other hand, we were
able to optimize different dimers with head-to-tail interactions,
and antiparallel and displaced - interactions (supporting
Figure SC4). For all such structures, we estimated the
interaction energies for the dimers in E-E, E-Z and Z-Z isomeric
pairs. Interestingly, the introduction of Z-isomeric component in
the dimeric structures (ZE and ZZ) led to progressive
destabilization of the dimers. The order of stabilization of dimeric
non-covalent complexes in 1d is as follows E-E > E-Z > Z-Z.
Based on this, it is apparent that the E-Z photoisomerization can
destabilize the intermolecular interactions that in turn cause the
phase transition. Again, the presence of Z-isomer in the molten
state hinders the freezing. On the other hand, under irradiation
conditions, the Z-isomer can be converted back to E-isomer, and
influence the crystallization.
We are grateful to the Science and Engineering Research Board
(SERB), New Delhi for the financial support (EMR/2014/000780).
We are also thankful to IISER Mohali for the financial support,
the departmental and central research facilities and also the
NMR, HRMS and other instrumentation support. SD and PK
thank UGC and CSIR for Research Fellowships, respectively.
AS and CS thanks IISER Mohali for the research fellowships.
We extend our sincere thanks to Dr. Santanu K. Pal and Indu
Bala for their help in collecting POM data. We thank Dr.
Angshuman Roy Choudhury and Mayank Joshi for helping in the
XRD data collection. Also, we acknowledge Dr. Sabyasachi
Rakshit for helping us with UV-Vis kinetics measurments.
Keywords: Azoheteroarenes • Photoswitching • Isomerization •
Phase transition • Photochromism
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min (21.4 days), which is nearly half of the values observed in DMSO-
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= 27.7 ±
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enough for the phase transition.
[23] Both the native yellow solid as well as the molten red liquid of 1d have
been subjected to infrared spectroscopic studies using ATR method.
Minor broadening of few of the signals, and splitting of one of the bands
were observed. On comparing with the computed IR spectral data, a
possible Z-isomer formation has been envisaged. The spectral data are
available in the Supporting Figure S11.
[24] The 1H-NMR spectral data of the molten sample (from 4 mg of 1d after
irradiation for 30 seconds) obtained after subjecting to 365 nm
irradiation showed 16% Z-isomer. The spectral data is available in the
Supporting Figure S12.
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[16] Computational studies have been performed using Gaussian 09 suite of
program. All the structures have been optimized to minima or first order
saddle points, and confirmed using frequency calculations. All the
relevant data from the computations and also the appropriate
references are provided in the supporting information (Supporting
Sections S9, S10 and S16).
[17] In our earlier work (ref. 7c), the N-methyl pyrazole and NH-pyrazole
based arylazopyrazoles with meta substitutions have been studied in
detail. For comparison, we have specifically chosen the meta-
substituted arylazoisoxazoles and their properties have been explored.
[18] For understanding the thermal stability of the Z-isomer, we followed the
Z-E reverse isomerization kinetics of few derivatives using UV-Vis
spectroscopy. The preliminary results suggested that the room
temperature thermal isomerization is found to be extremely slow.
Hence, the experiments were performed at higher temperature (80 ± 2
oC) in DMSO to determine the rate constants for the selected
derivatives, and the kinetics data are available in the supporting
information (Supporting Figure S7 and Table S8).
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Pravesh Kumar, Anjali Srivastava,
Chitranjan Sah, Sudha Devi and
Sugumar Venkataramani*
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Arylazo-3,5-dimethylisoxazoles –
Azoheteroarene photoswitches
exhibiting high Z-isomer stability,
solid state photochromism and
reversible light-induced phase
transition
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