Clean photodecomposition of 1-methyl-4-phenyl-1 H-tetrazole-5(4 H)-thiones to carbodiimides proceeds via a biradical

Article abstract of DOI:10.1021/jo1019859

The photochemistry of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxyphenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b) was studied in acetonitrile at 254 and 300 nm, which involves expulsion of dinitrogen and sulfur to form the respective carbodiimides 5a,b as sole photoproducts. Photolysis of the title compounds in the presence of 1,4-cyclohexadiene trap led to the formation of respective thioureas, providing strong evidence for the intermediacy of a 1,3-biradical formed by the loss of dinitrogen. In contrast, a trapping experiment with cyclohexene provided no evidence to support an alternative pathway of photodecomposition involving initial desulfurization followed by loss of dinitrogen via the intermediacy of a carbene. Triplet sensitization and triplet quenching studies argue against the involvement of a triplet excited state. While the quantum yields for the formation of the carbodiimides 5a,b were modest and showed little change on going from a C ₆H₅ (1a) to mOMeC₆H₄ (1b) substituent on the tetrazolethione ring, the highly clean photodecomposition of these compounds to a photostable end product makes them promising lead structures for industrial, agricultural, and medicinal applications.

Full text of DOI:10.1021/jo1019859

pubs.acs.org/joc
Clean Photodecomposition of 1-Methyl-4-phenyl-1H-tetrazole-5(4H)-
thiones to Carbodiimides Proceeds via a Biradical
Olajide E. Alawode, Colette Robinson, and Sundeep Rayat*
Department of Chemistry, Kansas State University, 213 CBC Building, Manhattan, Kansas 66506,
United States
sundeep@ksu.edu
Received October 7, 2010
The photochemistry of 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxyphenyl)-
4-methyl-1H-tetrazole-5(4H)-thione (1b) was studied in acetonitrile at 254 and 300 nm, which
involves expulsion of dinitrogen and sulfur to form the respective carbodiimides 5a,b as sole
photoproducts. Photolysis of the title compounds in the presence of 1,4-cyclohexadiene trap led to
the formation of respective thioureas, providing strong evidence for the intermediacy of a 1,3-biradical
formed by the loss of dinitrogen. In contrast, a trapping experiment with cyclohexene provided no
evidence to support an alternative pathway of photodecomposition involving initial desulfurization
followed by loss of dinitrogen via the intermediacy of a carbene. Triplet sensitization and triplet
quenching studies argue against the involvement of a triplet excited state. While the quantum yields
for the formation of the carbodiimides 5a,b were modest and showed little change on going from a
C6H5 (1a) to mOMeC6H4 (1b) substituent on the tetrazolethione ring, the highly clean photode-
composition of these compounds to a photostable end product makes them promising lead structures
for industrial, agricultural, and medicinal applications.
Introduction
reactions,8,9 and pharmaceutical agents.10 Despite their
widespread applications, studies on their structure and re-
activity are limited, and a better understanding of the
photochemistry of these ring systems is critical for designing
compounds with improved performance. For instance,
photostability of the tetrazolethione ring is of prime concern in
exploiting these scaffolds for the synthesis of novel pesticides or
pharmaceutical agents. It is therefore important to identify
any unwanted phototoxic intermediates/products that may
form upon UV exposure of these compounds and thus enable
strategies for preventing those decomposition pathways and
ensure greater photostability. On the other hand, in photo-
lithography where tetrazolethione scaffolds have been pro-
posed for the in situ photogeneration of carbodiimides that
subsequently react with carboxylic acids to form deep UV
resists,7 high photolability of the tetrazolethione rings is
Compounds containing a tetrazolethione scaffold have
attracted attention as corrosion inhibitors,1-3 pesticides,4
stabilizers in photography,5,6 UV resists in photolithog-
raphy,7 capping agents in semiconductor photocatalytic
(1) Mihit, M.; Salghi, R.; El Issami, S.; Bazzi, L.; Hammouti, B.; Ait
Addi, E.; Kertit, S. Pigm. Resin Technol. 2006, 35, 151.
(2) Mihit, M.; El Issami, S.; Bouklah, M.; Bazzi, L.; Hammouti, B.; Ait
Addi, E.; Salghi, R.; Kertit, S. Appl. Surf. Sci. 2006, 252, 2389.
(3) Essoufi, H.; Kertit, S.; Hammouti, B.; Benkaddour, M. Bull. Electrochem.
2000, 16, 205.
(4) Foldenyi, R. Monatsh. Chem. 1995, 126, 1035.
(5) Eachus, R. S.; Muenter, A. A.; Pawlik, T. D.; Lenhard, J. R. J. Phys.
Chem. B 2005, 109, 10126.
(6) Tamura, M.; Hada, H.; Noguchi, J.; Hayashi, S. J. Phys. Chem. 1962,
66, 559.
(7) Taylor, J. W.; Jiang, Y.; Bassett, D. R. Polym. Mater. Sci. Eng. 1991,
64, 50.
(8) Uchihara, T.; Kamiya, T.; Maedomari, S.; Ganeko, M.; Kinjo, S.;
Tamaki, Y.; Kinjo, A. J. Photochem. Photobiol., A 2000, 130, 63.
(9) Wang, C.-y.; Liu, C.-y.; Shen, T. J. Photochem. Photobiol., A 1997,
109, 65.
(10) Nesmerak, K.; Pospisek, M.; Nemec, I.; Waisser, K.; Gabriel, J. Folia
Microbiol. 2000, 45, 138.
216 J. Org. Chem. 2011, 76, 216–222
Published on Web 12/13/2010
DOI: 10.1021/jo1019859
r
2010 American Chemical Society

Alawode et al.
JOCArticle
desirable, so that carbodiimides can be generated cleanly,
quickly, and efficiently. Again, conclusive information about the
various photochemical processes is required as the undesirable
pathways may interfere with the formation of carbodiimides
and therefore would need to be suppressed in order to increase
the overall efficiency of the process.
SCHEME 1. 1-Methyl-4-phenyl-1H-tetrazole-5(4H)-thiones
1a,b
There are a few reports in the literature that discuss the
photochemistry of these heterocycles. For instance, work by
Dunkin and co-workers in 1989 revealed that the photolysis
of tetrazolethiones in a low-temperature matrix yields car-
bodiimides as a result of loss of dinitrogen and sulfur.11
Several years later, the photochemistry of this ring system
was revisited by Fausto et al., who reported that carbodi-
imides are not the only products in the gas phase and a variety
of other photoproducts are formed.12 The photolysis of
1-methyl-1H-tetrazole-5(4H)-thione in a low-temperature
argon matrix was found to proceed via three decomposition
pathways involving (1) the expulsion of dinitrogen to form
1-methyl-1H-diazirene-3-thiol, (2) the cleavage of the tetra-
zolethione ring to form methylisothiocyanate and the azide,
and (3) the concurrent expulsion of dinitrogen and sulfur to
form N-methyl carbodiimide.12 The authors also reported
that the primary photoproducts underwent further decom-
position to form methyl diazene, carbon monosulfide, and
nitrogen hydride.12 However, in solution the photolysis of
tetrazolethiones is known to form the corresponding carbo-
diimides or their tautomers as the sole products.13-15
insights into the mechanism of their photodecomposition
(Scheme 1).
Results and Discussion
Synthesis of Tetrazolethiones 1a,b and Their Absorption
Spectra. 1,3-Dipolar cycloaddition of phenylisocyanate (2a)
with trimethylsilylazide resulted in the formation of 1-phen-
yl-1H-tetrazol-5(4H)-one (3a).18 Compound 3a was meth-
ylated with dimethyl sulfate to obtain the tetrazolone 4a,
which upon treatment with phosphorus pentasulfide yielded
the desired 1-methyl-4-phenyl-1H-tetrazole-5(4H)-thione
(1a).19 Similarly, 3-methoxyphenylisocyanate (2b) was con-
verted to 4b as reported earlier,20 which was subjected to
thionation to obtain the desired 1-(3-methoxyphenyl)-4-
methyl-1H-tetrazole-5(4H)-thione (1b) (Scheme 2).
SCHEME 2. Synthesis of 1-Methyl-4-phenyl-1H-tetrazole-
5(4H)-thiones 1a,b
To the best of our knowledge there are no reports on the
mechanism of the photodecomposition of tetrazolethiones.
A few mechanistic studies on the related tetrazolones are
known.16,17 For instance, Cristiano and co-workers studied
the photochemistry of 1-allyl-4-phenyltetrazolones in solu-
tion that resulted in the formation of pyrimidinones as the
major product, which underwent decomposition in nonalco-
holic solvents to form secondary photoproducts such as allyl
amine, aniline, phenyl isocyanate, and allyl isocyanate.17 This
photochemistry is believed to involve an intermediacy of a
1,3-triplet biradical formed via the elimination of molecular
nitrogen from the photoexcited 1-allyl-4-phenyltetrazolones.17
Cristiano also investigated the photochemistry of 5-allyloxy
tetrazoles in solution and reported the formation of 1,3-oxazines
as the sole primary photoproducts that undergo further reac-
tions leading to the formation of hydrazines, enamines, aniline,
and phenyl isocyanate.16 Laser flash photolysis experiments
further revealed that photodecomposition of 5-allyloxy tet-
razoles involves the formation of triplet 1,3-biradicals.16
We were interested in exploring if the mechanism of photo-
decomposition of tetrazolethiones also proceeds through a
1,3-biradical, analogous to the tetrazolones, or if another type of
intermediate is involved. Therefore, we synthesized 1-methyl-4-
phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxy-
phenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b), investigated
their photochemistry in acetonitrile, and gained preliminary
The UV spectral data of 1a has been reported,19 and the
spectra of compound 1b in cyclohexane, tetrahydrofuran,
and acetonitrile are shown in Figure 1. Analogous to 1a, four
UV bands λ1-λ4 were observed for 1b in cyclohexane and
MeCN; however, λ4 could not be observed in THF due to
solvent interference (Figure 1). The corresponding values of
molar absorptivities for these bands are shown in Table 1.
λ1 and λ2 underwent slight blue shifts as the polarity of the
solvent was increased from cyclohexane f THF f MeCN.
λ3 of 1b remained unchanged, whereas λ4 showed a blue shift
from cyclohexane f MeCN. Time dependent density func-
tional calculations revealed that all bands in 1a19 and 1b result
from π f π* transitions with some degree of intramolecular
(11) Dunkin, I. R.; Shields, C. J.; Quast, H. Tetrahedron 1989, 45, 259.
(12) Gomez-Zavaglia, A.; Reva, I. D.; Frija, L.; Cristiano, M. L.; Fausto,
R. J. Mol. Struct. 2006, 786, 182.
(13) Quast, H.; Nahr, U. Chem. Ber. 1985, 118, 526.
(14) Quast, H.; Bieber, L. Chem. Ber. 1981, 114, 3253.
(15) Quast, H.; Nahr, U. Chem. Ber. 1983, 116, 3427.
(16) Frija, L. M. T.; Khmelinskii, I. V.; Serpa, C.; Reva, I. D.; Fausto, R.;
Cristiano, M. L. S. Org. Biomol. Chem. 2008, 6, 1046.
(17) Frija, L. M. T.; Khmelinskii, I. V.; Cristiano, M. L. S. J. Org. Chem.
2006, 71, 3583.
(18) Tsuge, O.; Urano, S.; Oe, K. Reactions of trimethylsilyl azide with
heterocumulenes. J. Org. Chem. 1980, 45, 5130.
(19) Rayat, S.; Chhabra, R.; Alawode, O.; Gundugola, A. S. J. Mol.
Struct. 2009, 933, 38.
(20) Rayat, S.; Alawode, O.; Desper, J. CrystEngComm 2009, 1892.
J. Org. Chem. Vol. 76, No. 1, 2011 217

Alawode et al.
JOCArticle
charge transfer (ICT) within the molecules (see Supporting
Information for 1b).
Product Analysis. The photolyses of argon-saturated solu-
tions of 1a,b in acetonitrile was carried out at 254 and 313 nm
in a quartz cuvette. The UV spectral changes as a function of
wavelength for compounds 1a and 1b at different irradiation
times (as reported in the Experimental Section) are shown in
Figures 2 and 3, respectively. The observance of clean isosbestic
points in each case suggested the formation of a single
photoproduct.
In order to identify the product(s), the photochemistry of
argon-saturated solutions of 1a,b in acetonitrile-d3 was studied
in a quartz NMR tube at 254 and 300 nm. The NMR spectrum
of tetrazolethiones taken at different irradiation times in-
dicated a clean photochemical reaction resulting into the
formation of carbodiimides 5a,b with the loss of dinitrogen
and sulfur from the heterocyclic ring (Scheme 3, see Figures
S4 and Figure S5 in Supporting Information). The NMR
peaks corresponding to the respective carbodiimides were
assigned by comparison of their chemical shift values to
those of authentic samples. The formation of carbodiimides
as the primary photoproduct was consistent with the result
reported by Quast.13-15 The photolyses were only carried
out for 15 and 60 min at 254 and 300 nm, respectively. The
FIGURE 1. Absorption spectra of 1b in cyclohexane (red), THF
(green), and acetonitrile (blue).
TABLE 1. Energies (λ (Ε)) and Molar Absorptivities (log ε) for Peaks
Observed in the Absorption Spectra of 1b in Cyclohexane,
Tetrahydrofuran, and Acetonitrile
cyclohexane
THF
λ (Ε)a
MeCN
λ (Ε)a
λ (Ε)a
log εb
log εb
log εb
λ1 290.0 (4.27)
λ2 266.0 (4.66)
λ3 222.0 (5.58)
λ4 207.0 (5.98)
3.82
3.89
4.31
4.27
285.0 (4.35)
264.0 (4.69)
223.0 (5.55)
3.97
4.03
4.40
281.0 (4.41)
260.0 (4.77)
221.0 (5.61)
196.0 (6.32)
3.82
3.90
4.34
4.15
aIn nm (eV). bIn M-1 cm-1
FIGURE 2. Changes in the UV spectrum of 1a induced by irradiation at 254 (left) and 313 nm (right) in acetonitrile (arrows indicate the
direction of spectral change upon irradiation).
FIGURE 3. Changes in the UV spectrum of 1b induced by irradiation at 254 (left) and 313 nm (right) in acetonitrile (arrows indicate the
direction of spectral change upon irradiation).
218 J. Org. Chem. Vol. 76, No. 1, 2011

Alawode et al.
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SCHEME 3. Photochemical Conversion of Tetrazolethiones
1a,b to Carbodiimides 5a,b
SCHEME 4. Two Possible Mechanistic Pathways for the
Photodecomposition of 1a,b
TABLE 2. Unreacted 1a,b (%), Products 5a,b (%), and Quantum
Yields (Φ) for the Photodecomposition in MeCN
yield
of
irradiation
time
unreacted
1a [%]
λ
5a [%]
Φ
1a 254
15
15
60
60
15
15
60
60
Ar-purged
O2-satd
Ar-purged
O2-satd
Ar-purged
O2-satd
Ar-purged
O2-satd
57
55
>95
>95
60
57
>95
>95
44
47
trace
trace
42
45
trace
trace
0.045
300
1b 254
300
0.031
SCHEME 5. Formation of Thioureas 8a,b during the Photolysis
of 1a,b in the Presence of 1,4-CHD via the Intermediacy of
1,3-Biradical 7a,b
aAmounts calculated by NMR spectroscopy with 1,4-dioxane as an
internal standard (average of three irradiated samples). The standard
deviation was in the range 0.4-2% and was calculated from three
separate irradiated samples in each case.
amount of 1a,b that remained unreacted after irradiation and
yields of corresponding products 5a,b are listed in Table 2.
There were trace amounts of other photoproducts (<5%)
that also formed during the photolysis of 1a,b at 254 nm (see
Figures S4 and S5 in Supporting Information). Their chem-
ical shift values suggest that these may correspond to
methyl isothiocyanate, corresponding aryl azides or benzi-
midazolethiones formed from the photodecomposition of
1a,b. Note that these type of photoproducts have been pre-
viously detected in the photolysis of tetrazolethiones in the
gas phase12 as well as in the photodecomposition of their
5-oxo derivatives.21 Only trace amounts of 5a,b were formed
after 60 min of exposure to 300 nm UV light. This was attributed
to the low molar absorptivities of 1a,b at that irradiation
wavelength.
The quantum yields for the formation of 5a,b were deter-
mined at 254 nm by using the azoxybenzene actinometer22
and are reported in Table 2. Overall, the quantum yields were
found to be modest, which indicates that the compounds might
be involved in radiationless decay or fluorescence.
Furthermore, we investigated the formation of secondary
photoproducts by irradiating the authentic samples of 5a,b in
acetonitrile-d3 at 254 nm. The NMR spectrum recorded at
120 min of irradiation showed no decomposition, thus indicating
that carbodiimides were stable photoproducts. This end pro-
duct photostability is a desirable feature from an applica-
tions standpoint.
dinitrogen, and path B, which involves the expulsion of
dinitrogen followed by desulfurization (Scheme 4). The
former pathway will involve the formation of a heterocyclic
carbene 6 as intermediate, whereas the latter will lead to the
formation of biradical 7 as the reactive species. In order to
distinguish between these two mechanistic pathways, we carried
out the experiments described below.
Investigating the Intermediacy of a Carbene. In order to
explore the intermediacy of a heterocyclic carbene 6 in the
photodecomposition, we carried out the photolyses of ar-
gon-purged solutions of 1a and 1b in acetonitrile-d3 contain-
ing an excess of cyclohexene at 254 and 300 nm. The expectation
wasthatifphotochemistrytookplacethroughthe intermediacy
of a carbene, it could be trapped by cyclohexene to form the
typical carbene addition product. However, analyses of the
crude reaction mixture by NMR spectroscopy and ESI-MS/MS
did not indicate the formation of product corresponding to
the trapped carbene.
Investigating the Intermediacy of a Biradical. Next, we con-
sidered the possibility that the photochemistry could proceed
through the intermediacy of a 1,3-biradical. The photolyses of
argon-purged solutions 1a,b in acetonitrile-d3 were carried out in
the presence of a hydrogen atom donor, 1,4-cyclohexadiene
(1,4-CHD), at 300 nm. We predicted that if the photoreaction of
1a,b occurred through the intermediacy of a biradical, it could
be trapped by 1,4-CHD prior to expulsion of sulfur, yielding a
thiourea reduction product. Indeed, the NMR spectroscopic
analyses of the reaction mixture indicated the formation of
thioureas 8a,b as major product (Scheme 5). In addition,
Mechanism of Photodecomposition. The formation of car-
bodiimides 5 from tetrazolethiones 1 involves the loss of
dinitrogen and sulfur. Therefore, there are two possible photo-
decomposition pathways that must be considered: Path A,
which involves desulfurization followed by elimination of
(21) Frija, L. M. T.; Reva, I. D.; Gomez-Zavaglia, A.; Cristiano, M. L. S.;
Fausto, R. Photochem. Photobiol. Sci. 2007, 6, 1170.
(22) Bunce, N. J.; LaMarre, J.; Vaish, S. P. Photochem. Photobiol. 1984,
39, 531.
J. Org. Chem. Vol. 76, No. 1, 2011 219

Alawode et al.
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FIGURE 4. Plot showing an increase in the amount of thioureas 8a (left) and 8b (right) with an increase in the concentration of 1,4-CHD
during the photolysis of 1a and 1b in acetonitrile, respectively.
FIGURE 5. Modest quenching of carbodiimides 5a (right) and 5b (left) during the photolysis of 1a and 1b in the presence of biphenyl,
respectively.
trace amounts of the respective carbodiimides 5a,b were also
formed. Our studies demonstrated that as the concentration of
1,4-CHD was increased the yield of thiourea also increased
(Figure 4). The formation of thioureas 8a,b as the major
products during the photolysis of 1a,b in the presence of 1,4-
CHD is suggestive of the intermediacy of a 1,3-biradical 7a,b in
the photodecomposition of the title compounds. While this
trapping experiment strongly implicates the intermediacy of a
biradical, it does not provide definitive evidence for whether the
biradical exists in its triplet or singlet spin multiplicity. However,
since singlet biradicals are known to be extremely short-
lived,23,24 in all probability the trapped species is the triplet
biradical since these have lifetimes long enough to react with
externally added traps.25 In addition, desulfurization from a
triplet biradical 7a,b to produce carbodiimide 5a,b will yield a
ground state triplet sulfur atom (3P)26 that is energetically more
favorable than desulfurization from a singlet biradical 7a,b,
which will lead to the formation of an excited state singlet sulfur
atom (1D). We believe that the lost sulfur atoms become S8
as this is the most common allotrope of sulfur.27 This argument
is further supported by the yellow coloration of the reaction
mixture produced after photolysis, which is suggestive of S8
formation.
argon-purged solutions of 1a,b in acetonitrile-d3 at 300 nm in
the presence of triplet sensitizers of varying energies (e.g.,
benzophenone, acetophenone, and acetone). The analyses of
the reaction mixture by NMR spectroscopy after 60 min of
irradiation revealed that no carbodiimides 5a,b were formed,
and therefore no photosensitization was observed. In order
to rule out the possibility of high lying triplet state, we also
performed the photolyses at 300 nm in the presence of a
triplet quencher, e.g., biphenyl (Figure 5). Our results indicate
thatastheconcentrationofbiphenylwasincreased,the yields of
carbodiimide were only slightly decreased. This minimal
decrease in the yield of photoproduct in the presence of a
quencher could be explained by a slight competitive absorp-
tion of the quencher at 300 nm. Photolyses of the oxygen-
saturated solutions of 1a,b in acetonitrile-d3 were also carried
out at 254 and 300 nm. The conversion of the tetrazolethiones
and the product yields were found to be almost identical to
those of the argon-saturated solutions, indicating that the
effect of the oxygen on the photochemistry of tetrazolethiones
was negligible (Table 2).
The inability to detect any photoproducts during triplet
sensitization of 1a,b, as well as only a modest inhibition of
carbodiimide formation observed in the triplet quenching
experiments with biphenyl, does not provide strong support
for the intermediacy of a triplet excited state. Given that our
computations indicate that the excited state of 1a,b is of π,π*
nature19 (Supporting Information), this may be due to a slow
rate of intersystem crossing relative to singlet bond scission
(1π,π* f 3π,π* intersystem crossings are frequently slowed
as a result of this being a spin-orbit coupling “forbidden”
conversion28). Although negative results do not provide
conclusive evidence, dissociation of dinitrogen from the
singlet excited state seems more plausible.
Investigating the Involvement of a Triplet Excited State.
Since the 1,4-CHD trapping experiments were suggestive
of a triplet biradical intermediate, a plausible precursor to
such a species would be the triplet excited state of the
photoprecursor 1a,b. In order to explore the possibility of
photochemistry from a triplet excited state, we irradiated
(23) Hoyle, C. E.; Clark, S. C.; Viswanathan, K.; Jonsson, S. Photochem.
Photobiol. Sci. 2003, 2, 1074.
(24) Casey, C. P.; Boggs, R. A. J. Am. Chem. Soc. 1972, 94, 6457.
(25) Bucher, G.; Mahajan, A. A.; Schmittel, M. J. Org. Chem. 2008, 73,
8815.
(26) Breckenridge, W. H.; Taube, H. J. Chem. Phys. 1970, 53, 1750.
(27) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements, 2nd ed;
Butterworth-Heinemann: Oxford, 1997.
(28) Turro, N. J. Modern Molecular Photochemistry; Benjamin/Cummings:
Menlo Park, 1978; p 628.
220 J. Org. Chem. Vol. 76, No. 1, 2011

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Conclusions
Note that the syntheses of 1a,b require TMSN3 and Me2SO4;
extreme caution must be taken during the handling of these
reagents because of their hazardous nature.
We have reported a clean photoconversion of 1-methyl-4-
phenyl-1H-tetrazole-5(4H)-thione (1a) and 1-(3-methoxy-
phenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b) to the cor-
responding photostable carbodiimides 5a,b. Analogous to
the 5-oxo derivatives of tetrazoles, the photodecomposition
5-thio derivatives occurs via the intermediacy of a 1,3-biradical
7a,b, which is believed to be in its triplet spin multiplicity. We
find no evidence for an alternative pathway involving a
carbene, wherein desulfurization occurs prior to loss of
dinitrogen. We were further interested in identifying the
nature of precursor that leads to this biradical. The photo-
sensitization and triplet quenching experiments argue against
the involvement of a triplet excited state. The obvious alternative
mechanistic pathway that could lead to the formation of a 1,3-
triplet biradical is a diradicaloid species generated directly from
the singlet excited state of 1a,b after the expulsion of dinitrogen.
Once formed, this diradicaloid species could be envisioned to
undergo intersystem crossing to generate the triplet biradical 7a,
b which then would undergo desulfurization to form 5a,b.
Overall, these studies indicate that 1a and 1b are highly
promising lead compounds for industrial, agricultural, and
medicinal applications. The search for derivatives with
improved quantum yields that retain the clean photochemistry
and end-product photostability of 1a,b would be of considerable
interest. Our mechanistic studies suggest that derivatives should
be sought that favor dinitrogen dissociation in the excited state,
since this appears to be the favored pathway in the photode-
composition of these compounds.
1-(3-Methoxyphenyl)-4-methyl-1H-tetrazole-5(4H)-thione (1b).
P2S5 (1.3 g, 5.8 mmol) was added to a solution of 4b (0.5 g,
2.4 mmol) in dry toluene (15 mL). The mixture was refluxed at
110 °C until the starting material disappeared. The reaction mixture
after filtration was concentrated under reduced pressure. Purifica-
tion by column chromatography (SiO2, hexane/ethyl acetate, 93:7)
gave 1b (0.42 g, 78% yield) as a white solid: Rf 0.64 (70:30 hexane/
ethyl acetate); mp 52-54 °C; FTIR (ATR) 1600, 1590, 1492, 1440,
1
1356, 1324, 1238, 1195, 1160, 1065, 1022, 865, 839, 782, 681. H
NMR (400 MHz, CD3CN): δ 7.53 (s, 1H), 7.51-7.49 (m, 1H),
7.46-7.43 (m, 1H), 7.13-7.10 (m, 1H), 3.89 (s, 3H), 3.85 (s, 3H).
13C NMR (400 MHz, CD3CN): δ 165.0, 161.0, 137.0, 131.2, 117.2,
116.2, 111.0, 56.4, 35.5. HRMS: exact mass calculated for (M þ Hþ)
C9H11N4OSþ=223.0654, found 223.0648; (M þ Naþ) C9H10-
N4OSNaþ = 245.0473, found 245.0468.
Spectroscopic Data. 1-Phenyl-1H-tetrazol-5(4H)-one (3a)18,19
.
White solid (1.67 g, 82%). H NMR (400 MHz, DMSO-d6):
1
δ 7.85 (d, J = 7.68 Hz, 2H), 7.56 (t, J = 7.60 Hz, 2H), 7.42 (t, J =
7.51 Hz, 1H). 13C NMR (400 MHz, DMSO-d6): δ 150.2, 134.1,
129.4, 127.5, 119.5.
1-Methyl-4-phenyl-1H-tetrazol-5(4H)-one (4a)19. Crystalline
solid (0.30 g, 91%). 1H NMR (400 MHz, DMSO-d6): δ 7.85 (d,
J = 8.27 Hz, 2H), 7.58 (t, J = 7.03 Hz, 2H), 7.44 (t, J = 7.40 Hz,
1H), 3.62 (s, 3H, CH3). 13C NMR (400 MHz, DMSO-d6):
δ 148.8, 134.2, 129.5, 127.7, 119.4, 31.2.
4-Methyl-1-phenyl-1H-tetrazole-5(4H)-thione (1a)19. Yellow
solid (2.30 g, 53%). 1H NMR (400 MHz, CD3CN): δ 7.89-7.85
(m, 2H), 7.63-7.55 (m, 3H), 3.89 (s, 3H). 13C NMR (400 MHz,
CD3CN): δ 165.1, 136.2, 130.8, 130.3, 125.3, 35.5.
1-(3-Methoxyphenyl)-1H-tetrazol-5(4H)-one (3b)20. Pale white
solid (0.52 g, 81% yield). 1H NMR (400 MHz, DMSO-d6):
7.47-7.41 (m, 3H), 6.98 (d, J = 4 Hz, 1H), 3.80 (s, 3H). 13C
NMR (400 MHz, DMSO-d6): 159.8, 150.2, 135.3, 130.4, 113.0,
111.3, 105.0, 55.4.
Experimental Section
General Procedures. Thin layer chromatography was carried
out on 250 μm silica gel plates, and UV light was used as a
visualizing agent. Standard column chromatography was per-
formed using 63-200 μm silica gel. 1H and 13C NMR spectra for
the structural characterization of the compounds were recorded
on 400 MHz NMR spectrometer. The carrier frequencies were
399.75 MHz (1H) and 100.53 MHz (13C). The number of scans
used was 64 for 1H NMR spectra and for 13C, ranging from 3-5 K
depending on the sample concentration. Both the 1H and 13C
spectra were recorded with longer relaxation time (10 s). Chem-
ical shifts and the coupling constants are reported in parts per
million and Hertz, respectively. All the quantitative analyses of
the photolyzed reaction mixtures were performed by NMR
spectroscopy with 1,4-dioxane as an internal standard.29 These
experiments were carried out on a 500 MHz NMR spectrometer
equipped with a 3 mm triple resonance inverse detection pulse
1-Methyl-4-(3-methoxyphenyl)-1H-tetrazol-5(4H)-one (4b)20.
Crystalline solid (0.50 g, 90%). 1H NMR (400 MHz, DMSO-d6):
7.49 - 7.43 (m, 3H), 7.15 (d, 1H), 3.81 (s, 3H), 3.61 (s, 3H). 13
C
NMR (400 MHz, DMSO-d6): 159.8, 148.7, 135.3, 130.6, 113.2,
111.3, 105.0, 55.5, 31.3.
The synthesis of the authentic samples is described below.
1-Methyl-3-phenylthiourea (8a)30. Prepared by a slight mod-
ification of the previously reported procedure. To a solution of
aniline (1.5 g, 16.1 mmol) in methanol (75 mL) was added methyl-
isocyanate (1.3 g, 17.7 mmol), and the reaction mixture was
stirred at 65 °C for 24-30 h. After the completion of the reaction,
solvent was removed by distillation under reduced pressure to
obtain crude product. Recrystallization in ethanol yielded 8a
(2.46 g, 92% yield) as white solid: Rf 0.29 (60:40 hexane/ethyl
acetate); mp 110-112 °C; FTIR (ATR) 3259, 3155, 2989, 2937,
1515, 1490, 1287, 1246, 1210, 1026, 1001, 723, 689, 640, 602. 1H
NMR (400 MHz, CD3CN): δ 8.12 (s, 1H), 7.41-7.37 (m, 1H),
7.29-7.22 (m, 3H), 6.56(s, 1H), 2.97 (d, J = 8 Hz, 3H). 13C NMR
(400 MHz, CD3CN): δ 182.8, 138.7, 130.4, 127.0, 126.0, 32.1.
1
field gradient probe operating at 499.848 MHz for H. The
spectra were an accumulation of 64 individual scans. The photo-
products were assigned by comparison of their chemical shift values
to that of authentic samples. The infrared frequencies are reported
in cm-1. High resolution mass spectra were acquired on a quadru-
pole/time-of-flight mass spectrometer. The samples were prepared
in methanol/acetonitrile (containing 0.1% formic acid in some
cases) and were introduced by continuous infusion into the electro-
spray ionization (ESI) source at a rate of 30 μL/min. TOF scans
were carried out in positive ionization mode. In most cases, both
[M þ H]þ and [M þ Na]þ ions were detectable for each species. All
irradiations were carried out in a Rayonet reactor at 254 nm and
broad band 300 nm UV light. Monochromatic 313 nm was obtained
by using broad band 300 nm UV lamps and by filtering the radiation
through a solution of 0.002 M K2CrO4 in 5% Na2CO3.
HRMS: exact mass calculated for (M þ Hþ) C8H11N2Sþ
167.0643, found 167.0637; (M þ Naþ) C8H10N2SNaþ
189.0462, found 189.0457.
=
=
1-(3-Methoxyphenyl)-3-methylthiourea (8b)31. Prepared as
previously reported.31 White solid (2.1 g, 87% yield); mp 98-
100 °C. 1H NMR(400 MHz, CD3CN): δ 8.06 (s, 1H), 7.29 (t, 1H),
6.88-6.78 (m, 3H), 6.62 (s, 1H), 3.78 (s, 3H), 2.97 (d, J = 8 Hz,
3H). 13C NMR (400 MHz, CD3CN): δ 182.7, 161.5, 139.7, 131.3,
(30) Ambati, N. B.; Anand, V.; Hanumanthu, P. Synth. Commun. 1997,
27, 1487.
(31) Vassilev, G. N.; Vassilev, N. G. Oxid. Commun. 2002, 25, 608.
(29) Peterson, J. J. Chem. Educ. 1992, 69, 843.
J. Org. Chem. Vol. 76, No. 1, 2011 221

Alawode et al.
JOCArticle
117.7, 112.5, 111.4, 56.1, 32.2. HRMS: exact mass calculated for
(M þ Hþ) C9H13N2OSþ=197.0749, found 197.0743; (M þ Naþ)
C9H12N2OSNaþ =219.0568, found 219.0563.
(10-50 equiv) were taken in quartz NMR tubes. The mixture in
each tube was purged with argon for 15 min and irradiated with
broad band 300 nm UV lamp for 60 min, and a NMR spectrum
was recorded.
Photosensitization and Triplet Quenching. The concentration
of 1a and 1b for the following experiments was approximately
4.63 mM in acetonitrile-d3.
N-((Methylimino)methylene)aniline (5a). Prepared by a dif-
ferent method than previously reported.32 Mercuric oxide (3.9 g,
18.1 mmol) was added to a solution of 8a (1.0 g, 6.0 mmol) in
CH2Cl2/H2O (4:1, 30 mL), and the mixture was stirred at room
temperature for 30 min. The reaction mixture was filtered
through Celite and washed with ample amounts of methylene
chloride. The filterate was concentrated under reduced pressure.
Purification by column chromatography (SiO2, hexane/ethyl acet-
ate, 95:5) gave 5a (0.1 g, 12% yield) as a yellow oil: Rf 0.83 (70:30
hexane/ethyl acetate); FTIR (ATR) 3059, 3024, 2935, 2879,
Three separate solutions of 1a,b (0.7 mL) in acetonitrile-d3
containing benzophenone, acetophenone, and acetone (1-20 equiv),
respectively, were taken in quartz NMR tubes, purged with argon
for 15 min, and irradiated with broad band 300 nm UV lamp for
60 min. Subsequently, a NMR spectrum was obtained.
Four separate solutions of 1a,b in acetonitrile-d3 (0.7 mL)
containing varying amounts of biphenyl (0-15 equiv) were
taken in different quartz NMR tubes. The mixture in each tube
was purged with argon for 15 min and irradiated with broad band
300 nm UV lamp for 60 min, and NMR spectrum was recorded.
Effect of Oxygen. An oxygen-purged solution of 1a,b (0.65 mL)
in acetonitrile-d3 (approximately in the range 4.63 mM) was irra-
diated in a quartz NMR tube at 254 and 300 nm for 15 and 60 min,
respectively, and NMR spectrum was recorded.
Actinometry. A 5.04 mM solution of azoxybenzene in 95%
ethanol and a 0.1 M solution of KOH in 95% ethanol were pre-
pared. The azoxybenzene solution was irradiated for 30 min in a
quartz cuvette at 254 nm (no purging with Ar required), and 1 mL
of the irradiated solution was mixed with 1 mL of 0.1 M KOH
solution followed by the addition of 8 mL of 95% EtOH in
a volumetric flask. A UV spectrum was subsequently recorded,
and the incident photons were calculated in mol/L/s as de-
scribed by Bunce et al.22 The quantum yields were calculated at
less than 10% conversions.
1
2121, 2026, 1592, 1499, 1406, 1282, 1156, 1070, 891. H NMR
(400 MHz, CD3CN): δ 7.33-7.29 (t, 2H), 7.14-7.09 (m, 3H),
3.14 (s, 3H). 13C NMR (400 MHz, CD3CN): δ142.0, 137.0, 130.5,
125.6, 124.4, 32.8. HRMS: exact mass calculated for (M þ Hþ)
C8H9N2þ = 133.0766, found 133.0760.
3-Methyl-N-((methylimino)methylene)aniline (5b). Similarly,
compound 5b (0.35 g, 42% yield) was obtained from 8b (1.00 g,
5.1 mmol). Purification by column chromatography (SiO2,
hexane/ethyl acetate, 95:5) gave 5b (0.35 g, 42% yield) as a yellow
oil: Rf 0.71 (70:30 hexane/ethyl acetate); FTIR (ATR) 2937, 2834,
2123, 1594, 1581, 1493, 1464, 1421, 1281, 1243, 1127, 1038, 945,
840, 769, 684 589. 1H NMR (400 MHz, CD3CN): δ 7.20 (t, 1H),
6.70 - 6.63 (m, 3H), 3.76 (s, 3H), 3.14 (s, 3H). 13C NMR (400
MHz, CD3CN): δ 161.6, 143.2, 136.7, 131.1, 116.7, 111.3, 109.9,
56.0, 32.8. HRMS: exact mass calculated for (M þ Hþ)
C9H11N2Oþ = 163.0871, found 163.0866.
Photochemistry. UV Spectral Changes. An argon-purged
solution of 1a (0.07 mM) and1b (0.13 mM) in acetonitrile was irra-
diated in a quartz cuvette at 254 nm. In the case of 1a, a UV spec-
trum was obtained after each irradiation at 0, 20, 40, 60, 120, 200,
300, and 420s, whereas in the case of 1b, a UV spectrum was
obtained after each irradiation at 0, 20, 40, 60, 80, 120, and 150s,
respectively. Similarly, the irradiation of an argon-purged solution
of 1a (0.2 mM) and 1b (0.075 mM) in acetonitrile was carried out in
a quartz cuvette at 313 nm, and a UV spectrum was obtained after
irradiation at different time intervals (at 0, 1, 5, 10, 15, 20, 30, 40, and
50 min for 1a and 0, 5, 10, 15, 20, 25, 25, 30, 35, and 40 min for 1b).
Product Analysis. An argon-purged solution of 1a,b (0.45 mL)
in acetonitrile-d3 (approximately in the range 4.63 mM) was
irradiated in a quartz NMR tube at 254 and 300 nm, and a NMR
spectrum was obtained at every 5 min time interval for 15 and
60 min, respectively.
Photolysis of Carbodiimides 5a,b. An argon-purged solution
of 5a,b (0.7 mL) in acetonitrile-d3 (approximately in the range
4.70 mM) was irradiated in a quartz NMR tube at 254 for 120 min,
and a NMR spectrum was obtained.
Photolysis in the Presence of Cyclohexene. An argon-purged
solution of 1a,b (0.7 mL) in acetonitrile-d3 (approximately in the
range 4.55 mM) containing 10 equiv of cyclohexene was irra-
diated at 254 and 300 nm in a quartz NMR tube for 30 and
60 min, respectively, and a NMR spectrum was obtained. For
the ESI-MS/MS experiments, the concentration of 1a and 1b
was in the range 1.5 mM. Eight milliliters of this solution was
irradiated at 254 and 300 nm. The solvent was removed on a
rotary evaporator and crude was analyzed.
Acknowledgment. Acknowledgment is made to the donors
of the American Chemical Society Petroleum Research Fund
for the partial support of the research described herein (ACS
PRF 48202-G4). This study was also supported in part by
grants from Kansas State University (start-up funds and
Innovative Research Award from the Terry C. Johnson Center
for Basic Cancer Research). The authors acknowledge Profes-
sor Ruth Welti and Ms. Pamela Tamura at the Kansas
Lipidomics Research Center (KLRC) for providing the mass
spectra on our compounds and Professor Om Prakash and
Mr. Alvaro Herrera for assistance with the 500 MHz NMR
experiments at the Biomolecular NMR facility, which is
supported by NIH (grants RR-025441 and RR-017686) and
KSU Targeted Excellence Programs.
Supporting Information Available: Theoretical calculations
on the electronic properties of 1b; computational methods;
resonance structures of 1b (Scheme S1); ground state geometry
of 1b (Figure S1); Cartesian coordinates for the optimized 1b;
experimental absorption spectra and TDDFT calculated verti-
cal excitations as stick spectra for 1b in cyclohexane, THF and
acetonitrile (Figure S2); molecular orbitals for the optimized
geometries of 1b in acetonitrile (Figure S3); TDDFT calcu-
lated vertical excitation energies, oscillator strengths, MO
character and transition type of 1b in cyclohexane, THF and
Photolysis in the Presence of 1,4-Cyclohexadiene. Four sepa-
rate solutions of 1a,b (approximately in the range 4.63 mM) in
acetonitrile-d3 (0.7 mL) containing varying amounts of 1,4-CHD
acetonitrile (Tables S1); NMR spectra of 1a,b before and after
1
irradiation at 254 nm (Figures S4 and S5); H NMR and 13
C
NMR spectra of 1b and 5b; 1H NMR spectra of 5a and 8a. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(32) Fell, J. B.; Coppola, G. M. Synth. Commun. 1995, 25, 43.
222 J. Org. Chem. Vol. 76, No. 1, 2011