Benzisoxazole 2-oxides as novel UV absorbers and photooxidation inhibitors

Article abstract of DOI:10.1002/poc.3161

Compounds with strong absorptions in the ultraviolet (UV) region of the spectrum, particularly the UVA and UVB, have seen much interest as UV screeners or absorbers in a wide variety of commercial products. A series of benzisoxazole 2-oxides have been synthesized and characterized by UV-vis spectroscopy. A number of derivatives have been shown to posses moderate to strong molar absorption coefficients in the UVB range (ca. 300 nm), the strongest being those derived from benzophenones. Three other derivatives containing additional electron withdrawing groups showed strong molar absorption coefficients in the UVA (ca. 340 nm). Solvent effects on the parent derivatives show changes in the molar absorption coefficients with little changes in the λ_max values. Preliminary studies of these compounds as potential additives to prevent photooxidation of polystyrene showed considerable inhibition of polymer degradation with the parent unsubstituted benzisoxazole 2-oxide compounds being the most effective. Copyright 2013 John Wiley & Sons, Ltd. A series of benzisoxazole 2-oxides have been shown to posses moderate to strong molar absorption coefficients in the UVB range (ca. 300 nm) and three others with strong absorptions on the UVA (ca. 340 nm). Solvent effects of the parent derivatives show changes in the molar absorption coefficients with little changes in the λ_max values. Preliminary studies of these compounds as potential additives to prevent photooxidation of polystyrene showed considerable inhibition of polymer degradation. Copyright

Full text of DOI:10.1002/poc.3161

Short Communication
Received: 3 April 2013,
Revised: 29 May 2013,
Accepted: 4 June 2013,
Published online in Wiley Online Library: 22 July 2013
(wileyonlinelibrary.com) DOI: 10.1002/poc.3161
Benzisoxazole 2-oxides as novel UV absorbers
and photooxidation inhibitors
Martin George Kocioleka* and Jerry S. Casbohma
Compounds with strong absorptions in the ultraviolet (UV) region of the spectrum, particularly the UVA and UVB,
have seen much interest as UV screeners or absorbers in a wide variety of commercial products. A series of
benzisoxazole 2-oxides have been synthesized and characterized by UV–vis spectroscopy. A number of derivatives
have been shown to posses moderate to strong molar absorption coefficients in the UVB range (ca. 300 nm), the
strongest being those derived from benzophenones. Three other derivatives containing additional electron with-
drawing groups showed strong molar absorption coefficients in the UVA (ca. 340 nm). Solvent effects on the parent
derivatives show changes in the molar absorption coefficients with little changes in the λmax values. Preliminary
studies of these compounds as potential additives to prevent photooxidation of polystyrene showed considerable
inhibition of polymer degradation with the parent unsubstituted benzisoxazole 2-oxide compounds being the most
effective. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: benzisoxazole 2-oxide; photodegradation; photooxidation; polystyrene; UV–vis spectroscopy
INTRODUCTION
ABSORPTION CHARACTERIZATION
Ultraviolet (UV) absorbers are compounds that show a strong
band of absorption of UV radiation. UV radiation can be
separated into three separate bands: UVA (320–400 NM), UVB
(280–320 NM) and UVC (100–280 NM). UV absorbers, particularly
those that absorb UVB, are extensively used in products subject
to degradation by sunlight and artificial sources of UV light such
polymers, paints and textiles.[1] Humans are also susceptible to
UVB radiation, which has been shown to catalyze the formation
of cyclobutane dipyrimidine dimers which result in gene muta-
tions.[2] As such, small molecules acting as UVB filters are used
in cosmetics, sunscreens and fabrics. For many years, UVA radia-
tion was considered less harmful than UVB; however, more
recent studies have provided evidence that it may be involved
in immunosupression,[3] photoaging[4] and DNA damage.[5]
Some common UV absorbers include benzophenones,[6,7]
cinnamic acids,[8,9] triazoles,[10,11] triazines[12–14] as well as other
heterocycles.[15–19] During the course of investigations into the
synthesis and properties of benzisoxazole 2-oxides, it was
proposed that these compounds may have potential as novel
UV absorbers. With this in mind, an examination of the
UV-absorbing properties and use of benzisoxazole 2-oxides as
photodegradation inhibitors was undertaken.
The UV spectra of benzisoxazole 2-oxides 1a-l were obtained in
ethanol at 5×10À5 M concentration (Fig. 1). The molar absorption
coefficients (ϵ) for maxima in each compound were calculated
and are shown in Table 1.
The results showed that a number of benzisoxazole 2-oxides
may have potential as UV filters. While all compounds showed
strong absorptions in the UVC region (239–275 nm), the most
interesting are those having absorptions in the UVA and UVB
regions. The 3-methyl benzisoxazole 2-oxides derived from
acetophenone, 1a–1e, all having moderate absorbance around
300 nm in the UVB with a shoulder about 10 nm higher than
the main absorbance. In addition, they all have a stronger absor-
bance around 270 nm that overlaps into the lower regions of
UVB. The 6-methoxy substituted benzisoxazole 1f has an absor-
bance around 300 nm, which is 1.5–2.0× stronger than other
benzisoxazole 2-oxides derived from acetophenones. Compounds
with added conjugation such as a nitro group 1g or additional
benzisoxazole 2-oxide ring 1h showed a bathochromic shift
resulting in strong absorption in the UVA region.
In contrast to those derived from acetophenones, the 3-phenyl
benzisoxazole 2-oxides derived from benzophenones showed
stronger molar absorption coefficients. Three of these com-
pounds, 1i, 1j and 1l, have strong absorptions in the UVB, while
the nitro derivative 1k has a strong absorption in the UVA.
It is well established that solvents can have an effect on both
the λmax and ϵ of the UV spectrum of a compound. The effect of
six different solvents on the UV absorbance of parent
PREPARATION OF BENZISOXAZOLE 2-OXIDES
The benzisoxazole 2-oxides under investigation were synthe-
sized as previously reported.[20] The appropriate acetophenones
and benzophenones were converted to the corresponding
oximes by treatment with hydroxylamine hydrochloride and
cyclized with iodobenzene diacetate (Scheme 1). Compounds
1a–h and 1l gave 1H and 13C NMR spectra identical to those
previously reported in the literature.[20–22] Compounds 1j and
1k were characterized by NMR and gave appropriate CHN
elemental analysis.
* Correspondence to: Martin George Kociolek, Penn State Erie, The Behrend
College, School of Science, Erie, PA, USA.
E-mail: mgk5@psu.edu
a M. G. Kociolek, J. S. Casbohm
School of Science, Penn State Erie, The Behrend College, Erie, Pennsylvania, USA
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M. G. KOCIOLEK AND J. S. CASBOHM
the less polar solvents such as hexanes, and to a lesser degree
diethyl ether, showed better resolution of the absorbances, with
what appears as a shoulder in ethanol becoming two distinct
peaks in the UVB region at 300 and 309 nm. For compound 1i,
the strongest absorbance was observed in diethyl ether,
followed by acetonitrile and DMSO.
INHIBITION OF POLYSTYRENE
PHOTOOXIDATION
Scheme 1. Synthesis of benzisoxazole 2-oxides 1a-l
The use of small organic molecules with absorbance in the UVB
region as stabilizers in polymers is of great interest. Over time
at ambient temperatures, polymers deteriorate through
autooxidation and photooxidation.[23,24] In order to prevent
degradation, additives such as antioxidants or other stabilizers
are often added. In order for these compounds to be useful, they
must possess three characteristics, they must (i) strongly absorb
UV radiation; (ii) harmlessly dissipate the energy they absorb and
benzisoxazole 2-oxides 1a and 1i at 6×10À5 M was undertaken
(Fig. 2). In the case of both compounds, the λmax wavelength
varied little with solvent, while the molar absorption coefficient
did vary slightly. In the case of 1a, the strongest absorptions
were in hexanes and dichloromethane. As would be expected,
Figure 1. UV spectra for compounds 1a-l
Table 1. Spectroscopy data for benzisoxazole 2-oxides 1a–1l
Compound
R
X
λ )
max/nm (ϵ/MÀ1 cmÀ1
1a
1b
1c
1d
1e
1f
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
5-Br
5-Cl
5-CH3
6-CH3
6-OCH3
6-NO2
270 (13140), 294 (7322)
275, (16566), 307 (8996)
274 (13332), 306 (7168)
271 (14923), 302 (7121)
271 (12803), 302 (9341)
275 (13332), 303 (13585)
246 (13554), 342 (15993)
258 (17620), 342 (7259)
1g
1h
1i
1j
1k
1l
Ph
Ph
Ph
H
243 (25342), 290 (15681)
252 (27363), 311 (12625)
271 (15583), 347 (10806)
239 (14407), 297 (12316)
6-OCH3
6-NO2
H
2-hydroxyphenyl
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BENZISOXAZOLE 2-OXIDES AS NOVEL UV ABSORBERS AND PHOTOOXIDATION INHIBITORS
Figure 2. UV spectra for 1a and 1i in various solvents
Figure 4. Carbonyl index vs. time for irradiation of polystyrene films
index, As the absorbance of the peak under study and Ar the
absorbance of the reference peak. Use of the carbonyl index
allows for comparison of films that vary in thickness. The results
of the studies are plotted as carbonyl index vs. time and are
shown in Fig. 4. In these plots, the larger ICO and/or larger slope
indicate a greater degree of degradation of the polystyrene film,
thus a less effective inhibitor. The results of the comparison of
two benzisoxazole 2-oxides compared to the two commercially
available inhibitors (Fig. 4a) showed 2 and 3 to be most effective
with 41 and 38% less degradation than polystyrene alone. While
not as effective as the commercially used inhibitors, benzisoxazole
2-oxides 1a and 1i still showed considerable inhibition of 26 and
31%, respectively.
A comparison of several derivative of benzisoxazole 2-oxides
derived from acetophenone (Fig. 4b) showed similar inhibition
for the parent 1a and chloro-substituted derivative 1c. Not unex-
pectedly, the two derivatives with absorbances in the UVA region
(242 nm) provided less inhibition. Bis-benzisoxazole 2-oxide 1h
was the least effective with the nitro derivative 1g, which had a
higher molar absorption coefficient at 242 nm, being somewhat
better. The methoxy derivative 1f gave the most unexpected
result, despite having strong absorbance in the UVB was a less
effective inhibitor than the parent 1a. A comparison of several
derivatives of benzisoxazole 2-oxides derived from benzophenone
(Fig. 4c) showed parent benzisoxazole 2-oxide 1i to be the most
Figure 3. Commercially used UV absorbers 2 and 3
(iii) persist in the matrix. A preliminary evaluation of the ability of
several of the benzisoxazole 2-oxides to prevent photodegradation
of polystyrene was undertaken. In order to evaluate the ability of
these compounds in this capacity, parent benzisoxazole 2-oxides
1a and 1i were compared to two commercial UV-absorbing inhib-
itors, 2-(2H-benzotriazole-2-yl)-4-methylphenol (2-Tinuvin P®) and
2′,4′-dihydroxybenzophenone (3-Univol 200®) (Fig. 3).
Polystyrene films (approximately 75 μM) containing 1% w/w of
inhibitor were irradiated with a UVB light, whose spectrum
ranged from 280 to 350 nm centered at 310 nm. The degree of
photooxidation of the polystyrene films was evaluated by moni-
toring the FT-IR spectrum (absorbance mode) of each film at
periodic intervals. In order to compare the degree of polystyrene
degradation, the amount of carbonyl formation resulting from
polymer backbone cleavage was observed as an increase in the
absorbance at 1720 cmÀ1. This increase was expressed using
the band index method[25] comparing the ratio of the carbonyl
peak at 1720 cmÀ1 to a reference peak at 906 cmÀ1. This ratio
was calculated by the formula ICO = As/Ar where Ico is carbonyl
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M. G. KOCIOLEK AND J. S. CASBOHM
6.93 (dd, J = 1.8, 6.6 Hz, 1H), 6.78 (d, J = 1.8 Hz, 1H), 3.89 (s, 3H); 13C NMR
(100 MHz, CDCl3) 161.3, 151.8, 129.9, 128.9, 127.6, 125.7, 120.9, 117.8,
113.1, 112.1, 92.0, 55.8; Anal. Calcd. for C14H11NO3: C, 69.70; H, 4.60; N,
5.81. Found: C, 69.56; H, 4.52; N, 5.70.
effective. Interestingly, the nitro derivative 1k and methoxy deriv-
ative 1j were only slightly less effective. By far, the least effective of
these derivatives was the hydroxy derivative 1l, despite having a
similar absorbance spectrum to 1i.
One possible explanation for the differences in inhibition
exhibited by substituted benzisoxazole 2-oxides may be
accounted for by their differences in photostability. The
isoxazole ring system is likely to undergo facile cleavage of the
N–O bond, and substitution on the ring may facilitate this ring
opening. While the exact mechanism for the photostabilization
of the benzisoxazole 2-oxides has not been established, it likely
they act as simple UV absorbers. However, unpublished work
from our lab has shown these compounds to undergo a rela-
tively facile electrochemical reduction, in part resulting in cleav-
age of the N–O bond. This could suggest the possibility of a
radical-scavenging mechanism to account for some inhibition
as well.
6-Nitro-3-phenyl-1,2-benzisoxazole 2-oxide (1k)
3-Phenyl-1,2-benzisoxazole 2-oxide (1i) (0.211 g, 1 mmol) was dissolved
in concentrated nitric acid (5 mL) and stirred at room temperature for
24 h. The solution was poured in to 25 mL of ice/water. The resulting
precipitate was vacuum filtered, dried and recrystallized from 50/50
ethanol/water resulting in pale yellow crystals of 1 k (0.148 g, 58%): m.p.
186–187 °C; 1H NMR (400 MHz, CDCl3): d 8.25 (dd, J = 2.0, 8.8 Hz, 1H), 8.13
(d, J = 2 Hz, 1H), 7.99 (m, 2H), 7.88 (d, J = 8.8 Hz, 1H), 7.65–7.56 (m, 3H); 13C
NMR (100 MHz, CDCl3): 149.3, 147.9, 130.8, 129.4, 127.7, 125.6, 124.3,
120.6, 119.6, 117.0, 103.0 Anal. Calcd. for C13H8N2O4: C, 60.94; H, 3.15;
N, 10.93. Found: C, 60.73; 3.07 H; N, 10.81.
UV spectroscopy
All UV spectra were obtained on a Cary 300Bio UV–Visible spectrometer.
Unless otherwise noted, all spectra were obtained in spectral grade
ethanol. Molar absorption coefficients were calculated over the concen-
tration range 1 × 10À4 to 5 × 10À6 M with all absorbance values obeying
the Beer–Lambert law.
CONCLUSIONS
Herein, the UV data for a series of benzisoxazole 2-oxides has
been presented along with a preliminary study of their use as
photooxidation inhibitors of polystyrene. The results indicate
the potential of these compounds as new class of UVB absorbers,
with the stronger absorbing compounds being those benzisoxazole
2-oxides derived from benzophenones. In addition, those com-
pounds with added conjugation have potential as UVA absorbers.
While the parent compounds themselves may absorb in the
moderate to strong range, one can envision combining the
benzisoxazole 2-oxide with other known UV absorbing groups to
enhance their absorbance. Their potential as inhibitors of photoox-
idation was also demonstrated in the case polystyrene films,
although not inhibiting as much as commercially available inhibi-
tors. These results are encouraging and warrant further investiga-
tion into other properties that would make these useful
stabilizers, including the mechanism of inhibition and the nature
of photodegradation and persistence in the polymer matrix. Further
development of more effective benzisoxazole 2-oxides inhibitors by
increasing their molecular weight may increase their stability and
limit depletion from the films during irradiation. Investigations into
the photodegradation and photochemistry of benzisoxazole 2-oxides
are currently underway.
Preparation of polystyrene films
Polystyrene beads (Acros, avg. MW 250,000)(5 g) were dissolved in CHCl3
(50 mL) with stirring at room temperature. To 10 mL of the polystyrene
solution was added 5 mg of the appropriate additive (with exception of
the control film) and the solution stirred at room temperature until
homogeneous. Using an Eppendorf pipette, 0.25 mL of the solution was
dropped into the center of a Petri dish floating in a bowl of water. The
dishes were covered and allowed to evaporate at room temperature
for 2 h at which time they were removed from the Petri dishes and the
films mounted on cardboard holders with a 0.5 cm hole. The films were
allowed to further evaporate for 24 h in the dark at room temperature.
The thickness of the films was measured by micrometer (MHC industrial)
as well by comparison of the IR spectrum to a standard sample of poly-
styrene with known thickness (50 μM). All experimental samples had
thickness of 75 ( 10) μM.
Photodegradation of polystyrene films
The polystyrene films were irradiated with a single UVB bulb (Spectroline-
UVB, BLE8T312) at a distance of 5 cm such that the incident UV radiation
was perpendicular to the samples. The light intensity at the samples was
measured to be 50 mW/M2, and the samples were rotated periodically to
ensure similar light intensity for each sample. At respective time intervals,
IR spectra (in absorbance mode) of the films were taken using a Nicolet
6700 FT-IR spectrometer. The absorption for peaks at 1720 cmÀ1 were
determined and used to monitor progression of photodegradation. A
EXPERIMENTAL
1H and 13C NMR spectra were obtained on a Bruker 400 MHz spectrome-
ter in solvents specified using TMS as an internal standard. Solvents and
reagents were obtained commercially and used without further
purification.
carbonyl index (Ico
) was calculated by using the absorbance at
906 cmÀ1 as a reference peak, where Ico = A1720/A906
.
Synthesis of benzisoxazole 2-oxides
1,2-Benisoxazole 2-oxides 1a–i and 1l have been previously reported and
were synthesized and characterized by the physical and spectral proper-
ties as reported in the literature.[20–22]
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