Photoinduced single electron transfer on 5-aryl-1,2,4-oxadiazoles: Some mechanistic investigations in the synthesis of quinazolin-4-ones

Article abstract of DOI:10.1021/jo990298f

The photochemistry of some 5-aryl-3-methoxy- (or 5-aryl-3-phenyl-) 1,2,4-oxadiazoles irradiated in the presence of different sensitizers [such as diphenylacetylene (DAC), 9,10-diphenylanthracene (DAN), or triphenylene (TPH)] or ground-state donors such as triethylamine (TEA) has been investigated. Intermediates arising from breaking of the ring O-N bond develop both into quinazolin-4-ones (by a heterocyclization reaction involving the aryl at the C-5 of the oxadiazole nucleus) and into open-chain products (corresponding to a reduction at the ring O-N bond), in different ratios depending on their structures and photoreaction conditions. A reasonable explanation considers sensitization by photoinduced electron transfer either from the sensitizer in its excited state to the oxadiazole in its ground state or from the electron donor reagent (TEA) to the excited oxadiazole; in both cases an oxadiazole radical anion is formed as a key species from which breaking of the ring O-N bond takes place. Reduction potentials of representative oxadiazoles confirm this hypothesis. Possible applications in the synthesis of variously substituted quinazolin-4-ones are recognized.

Full text of DOI:10.1021/jo990298f

7028
J . Org. Chem. 1999, 64, 7028-7033
P h otoin d u ced Sin gle Electr on Tr a n sfer on
5-Ar yl-1,2,4-oxa d ia zoles: Som e Mech a n istic In vestiga tion s in th e
Syn th esis of Qu in a zolin -4-on es
Silvestre Buscemi, Andrea Pace, and Nicolo` Vivona*
Dipartimento di Chimica Organica “E. Paterno`”, Universita` di Palermo, Viale delle Scienze,
Parco d’Orleans II, 90128 Palermo, Italy
Tullio Caronna
Dipartimento di Chimica, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
Alessandro Galia
Dipartimento di Ingegneria Chimica dei Processi e dei Materiali, Universita` di Palermo,
Viale delle Scienze, 90128 Palermo, Italy
Received February 17, 1999
The photochemistry of some 5-aryl-3-methoxy- (or 5-aryl-3-phenyl-) 1,2,4-oxadiazoles irradiated in
the presence of different sensitizers [such as diphenylacetylene (DAC), 9,10-diphenylanthracene
(DAN), or triphenylene (TPH)] or ground-state donors such as triethylamine (TEA) has been
investigated. Intermediates arising from breaking of the ring O-N bond develop both into
quinazolin-4-ones (by a heterocyclization reaction involving the aryl at the C-5 of the oxadiazole
nucleus) and into open-chain products (corresponding to a reduction at the ring O-N bond), in
different ratios depending on their structures and photoreaction conditions. A reasonable explanation
considers sensitization by photoinduced electron transfer either from the sensitizer in its excited
state to the oxadiazole in its ground state or from the electron donor reagent (TEA) to the excited
oxadiazole; in both cases an oxadiazole radical anion is formed as a key species from which breaking
of the ring O-N bond takes place. Reduction potentials of representative oxadiazoles confirm this
hypothesis. Possible applications in the synthesis of variously substituted quinazolin-4-ones are
recognized.
In tr od u ction
zoles substituted at C(3) with certain three-atom side
chains have also been reported.6 On the other hand, apart
from the above-mentioned photoreactions producing het-
erocyclic structures, photolytic intermediates can even
stabilize into open-chain products, e.g., by a reaction with
the nucleophilic solvent (methanol)7 or by a capture of
two hydrogen atoms from the medium (resulting in an
overall photoreduction reaction at the ring O-N bond).4,5
An interesting intramolecular photoreaction concerns
the formation of the quinazolin-4-one system by irradia-
tion of some 5-aryl-substituted 1,2,4-oxadiazoles at λ )
313 nm in methanol and in the presence of diphenyl-
acetylene (DAC).8 In this case, the heterocyclization
reaction of photolytic intermediates, whichever the ring
photolytic species may be, engages the C(5)-aryl moiety,
and a first-glance approach considered the photoreaction
as arising from a triplet sensitization.8
In the framework of our research on photoinduced
rearrangements of O-N bond containing five-membered
heterocycles, we have pointed out the possibility of
exploiting this photoreactivity to appoint alternative
methodologies for the synthesis of target compounds.1-5
Significant examples of this approach have concerned the
photochemistry of 1,2,5- and 1,2,4-oxadiazoles. In a
general pattern, photolytic species arising from cleavage
of the weakest O-N bond of these rings collapse into final
products depending, inter alia, on (i) its own structure,
(ii) the nature of the reagent that will be present, and
(iii) the possibility of subsequent heterocyclization of
primarily formed intermediates. Thus, for example, ir-
radiation of particular 1,2,4-oxadiazoles in the presence
of nitrogen or sulfur nucleophiles produces 1,2,4-tria-
zoles4 or 1,2,4-thiadiazoles,5 respectively, which assume
a heterocyclization reaction of intermediates arising from
the formation of a N-N or N-S bond. Intramolecular
photoinduced heterocyclizations involving 1,2,4-oxadia-
Following our studies, we now decided to concentrate
our attention on deeper mechanistic investigations of this
rearrangement, as well as on the potential of this
photochemical reaction in synthetic projects. To this aim,
* To whom correspondence should be addressed. Phone: +39 091
596903. Fax: +39 091 596825.
(6) (a) Buscemi, S.; Vivona, N. J . Heterocycl. Chem. 1988, 25, 1551.
(b) Buscemi, S.; Vivona, N. Heterocycles 1989, 29, 73. (c) Buscemi, S.;
Macaluso, G.; Vivona, N. Heterocycles 1989, 29, 1301. (d) Buscemi, S.;
Cusmano, G.; Gruttadauria, M. J . Heterocycl. Chem. 1990, 27, 861
(7) (a) Newman, H. Tetrahedron Lett. 1968, 2421. (b) Buscemi, S.;
Cicero, M. G.; Vivona, N.; Caronna, T. J . Heterocycl. Chem. 1988, 25,
931.
(1) Vivona, N.; Buscemi, S. Heterocycles 1995, 41, 2095.
(2) Buscemi, S.; Vivona, N.; Caronna, T. J . Org. Chem. 1995, 60,
4096.
(3) Buscemi, S.; Vivona, N.; Caronna, T. Synthesis 1995, 917.
(4) Buscemi, S.; Vivona, N.; Caronna, T. J . Org. Chem. 1996, 61,
8397.
(5) Vivona, N.; Buscemi, S.; Asta, S.; Caronna, T. Tetrahedron 1997,
53, 12629.
(8) Buscemi, S.; Vivona, N. J . Chem. Soc., Perkin Trans. 2 1991,
187.
10.1021/jo990298f CCC: $18.00 © 1999 American Chemical Society
Published on Web 08/31/1999

Electron Transfer on 5-Aryl-1,2,4-oxadiazoles
J . Org. Chem., Vol. 64, No. 19, 1999 7029
Sch em e 1a
) 313 nm) in the presence of triethylamine (TEA),
starting from the consideration that excited oxadiazole
could act as electron acceptor from the ground electron
donor reagent.
Resu lts a n d Discu ssion
Ir r a d ia tion s in th e P r esen ce of DAC, DAN, or
TP H. (a ) 3-Meth oxy-5-a r yl-1,2,4-oxa d ia zoles 1a -d
a n d 7a ,b. Irradiation of 3-methoxy oxadiazoles 1a -d in
methanol in the presence of DAC gave the expected8
quinazolinones 3a -d , which can be isolated in about 30-
40% yields. In addition, some amounts of photoreduction
products 5a -d were also formed. In a typical preparative
irradiation of 1a , besides starting material (40%), com-
pounds 3a (40%) and 5a (18%) have been isolated.
Oxadiazoles 1b-d behaved similarly, and gave 3b-d and
5b-d , respectively. However, a significant substituent
effect resulted: in fact, electron-withdrawing substitu-
ents at the C(5)-aryl moiety enhance both the photocon-
version of starting material and yields of reduction
products. (Typical results from parallel experiments are
reported in Table 2.) By contrast, parallel unsensitized
irradiation of the representative 1a at λ ) 313 nm in
methanol essentially returned starting material (92%),
while only a few percent of 3a and 5a have been detected
(by HPLC). Apart from compound 1c, triplet energy
transfer sensitization by DAC seems unlikely on ener-
getic grounds (see Table 1). On the other hand, by using
different triplet sensitizers [namely, acetophenone (Et )
310 kJ /mol)9 at λ ) 313 nm for 1a or benzophenone (Et
) 287 kJ /mol)9 at λ ) 365 nm for 1d ], no significant
sensitization was obtained. As expected, the DAC-
sensitized irradiation of oxadiazoles 7a ,b gave both the
forecast regioisomers 8a ,b (18 and 24%, respectively) and
9a ,b (15 and 30%). Again, the chloro-substituted sub-
strate 7b showed higher photoconversion and more
amounts of the reduction product 10b.
We have then looked at irradiations of the representa-
tive oxadiazole 1a in the presence of DAN which is known
to act as singlet sensitizer: since it has a very low yield
of intersystem crossing, practically no triplet DAN is
formed.10 Interestingly, a preparative-scale irradiation of
1a and DAN allowed 3a (52%) and 5a (12%) to be
isolated, testifying that DAN does act as an efficient
sensitizer. TPH behaved similarly: an analytical-scale
irradiation of 1a returned starting material (73%) and
gave 3a (20%) and 5a (7%) (Table 2).
(b) 3-P h en yl-5-a r yl-1,2,4-oxa d ia zoles 2a -c. Irra-
diation of these substrates in the presence of DAC gave
the quinazolin-4-ones 4a -c. However, differently from
previous oxadiazole derivatives, no significant amounts
of reduction products were obtained. Moreover, substit-
uents at the C(5)-aryl moiety do not appreciably affect
photoconversion of the starting oxadiazole. The formation
of compounds 4 may be considered as arising from a
DAC-sensitized process: in fact, when directly irradiated
in methanol, oxadiazoles 2a -c remained practically
unchanged. Again, the photoreaction also took place by
using DAN, or TPH: thus, a preparative DAN-sensitized
irradiation of the oxadiazole 2a furnished 4a (50%)
together with unreacted starting material, while instead
no significant amounts of the corresponding reduction
product 6a were detected. TPH behaved similarly (see
Table 2). By contrast, in the irradiation of the oxadiazole
2a in the presence of benzophenone (at λ ) 365 nm) or
a
(i) hν/MeOH/sensitizer.
Ta ble 1. En er gy Va lu es (k J /m ol) of th e Sin glet (Es) a n d
Tr ip let (Et) Sta tes for Com p ou n d s 1a -d a n d 2a -c [As
Deter m in ed fr om F lu or escen ce (in Meth a n ol) or
P h osp h or escen ce Em ission s (in Aceton itr ile)], a n d for
DAC,9 Da n ,9,10 a n d TP H9,11
compd
Es
Et
compd
Es
Et
1a
1b
1c
1d
2a
418
441
430
414
388
291
283
255
270
281
2b
2c
DAC
DAN
TPH
381
387
396
305
350
278
267
261
278
we have considered irradiations of some 3-methoxy-5-
aryloxadiazoles (1 and 7) and 3-phenyl-5-aryloxadiazoles
(2) (Scheme 1) in different photoreaction conditions.
Interestingly, oxadiazoles 1a -d and 7a ,b are character-
ized by having an OMe group at C(3) of the ring, and
this feature was expected to strongly affect the reactivity/
stability of photolytic intermediates. In their turn, oxa-
diazoles 7a ,b would give regioisomeric heterocyclizations,
so that, when various substituents at the C(5)-aryl moiety
would be considered, the synthesis of variously substi-
tuted quinazolin-4-ones could be accomplished. All oxa-
diazoles showed similar photophysical behavior with a
strong fluorescence emission and weaker phosphores-
cence. Values of singlet (Es) and triplet (Et) state energies
of representative substrates are given in Table 1. As for
photoreaction conditions, on the basis of previous reports
we initially considered irradiations (at λ ) 313 nm) in
methanol in the presence of DAC. In addition, to gain
more insight into the nature of sensitization, representa-
tive oxadiazoles were irradiated in the presence of 9,10-
diphenylanthracene (DAN) (at λ ) 365 nm) and triphen-
ylene (TPH) (at λ ) 313 nm). Energies of excited states
of DAC,9 DAN,9,10 and TPH9,11 are reported in Table 1.
Furthermore, selected oxadiazoles were irradiated (at λ
(9) Murov, S. L. Handbook of Photochemistry; Marcel Dekker: New
York, 1973.
(10) Wilson, T.; Schaap, A. P. J . Am. Chem. Soc. 1971, 93, 4126.
(11) Bartlett, P. D.; Engel, P. S. J . Am. Chem. Soc. 1968, 90, 2960.

7030 J . Org. Chem., Vol. 64, No. 19, 1999
Buscemi et al.
Ta ble 2. An a lytica l P h otor ea ction s. Ir r a d ia tion of Com p ou n d s 1a -d a n d 2a in Meth a n ol in th e P r esen ce of DAC, DAN,
or TP H. Qu a n tita tive HP LC An a lyses (%) of P h otolyza tes
starting material
photoproducts
photoproducts
compd
DAC
DAN
56
TPH
73
DAC
DAN
39
TPH
20
DAC
DAN
5
TPH
7
1a
1b
1c
1d
2a
70
85
31
52
85
3a
3b
3c
3d
4a
25
10
32
28
15
5a
5b
5c
5d
6a
5
5
37
20
0
69
89
31
11
0
0
Sch em e 2
acetophenone (at λ ) 313 nm), no significant sensitization
was obtained.
The formation of both the quinazolin-4-one system and
the open-chain reduction products may be considered as
arising from a sensitized photolysis of the 5-aryl-
substituted 1,2,4-oxadiazoles. However, the relevant
questions concern (i) the nature of sensitization, (ii) the
nature of the photolytic species which arises from break-
ing of the ring O-N bond, and (iii) how the structure of
substrate plays a role in the photoreaction.
In principle, heterolytic cleavage of the ring O-N bond
of excited oxadiazoles would give acyliminonitrenes.
These reactive intermediates can undergo chemistry from
either their singlet or their triplet states.12 Singlet
nitrenes (electrophilic in character) will be well disposed
to react both with the nucleophilic solvent and with the
C(5)-aryl moiety by a heterocyclization reaction. In turn,
triplet nitrenes are expected to stabilize preferentially
by capture of hydrogen atoms from the medium in an
overall reduction reaction.
photolytic species do react preferentially with the nitro-
gen nucleophile, giving N-N bonded species.4,13
A mechanistic hypothesis which could explain our
results considers sensitization by an electron-transfer
mechanism. Previously, photoinduced electron transfer
has been suggested to occur in the DAN-sensitized
decomposition of aroyl azides.14 By this hypothesis,
excited DAC, DAN, or TPH behaves as an electron donor
toward the electron-deficient ground-state oxadiazole,
which will then assume a radical anion form. Subsequent
breaking of the ring O-N bond will then take place from
this key intermediate, producing an open-chain species
for which a radical anion structure 16 (likely developing
into 17 in the hydroxylic solvent) can be presumed
(Scheme 3). The formation of open-chain radical anion
via an electron-transfer mechanism has been suggested
in the iron dichloride- or samarium diiodide-induced
reductive breaking of the ring O-N bond of some iso-
xazoles.15,16 On the other hand, nitrene radical anions are
suggested in electrochemical reduction17 of azides or in
their photoinduced decomposition by an electron-transfer
mechanism.18 Our ring-cleaved intermediate will develop
into both the quinazolin-4-one system (implying a back-
electron transfer in some of the subsequent steps) and
the reduced products (by hydrogen atom abstraction), in
On the basis of our results, involvement of triplet
energy-transfer sensitization appears unlikely. On the
other hand, singlet energy transfer by DAN or TPH
might be excluded on energetic grounds (see Table 1).
Moreover, although an intramolecular heterocyclization
might be favored entropically over an intermolecular
reaction involving the solvent, ground-state singlet ni-
trenes would have been captured to some extent by the
solvent (methanol); however, this last reaction was not
significantly observed in all our sensitized procedures:
only in the case of the oxadiazole 11, the DAC-sensitized
photoreaction, besides 13, gave trace amounts of the
methanol addition compound 12 (Scheme 2). Indeed,
methanol addition reaction to presumed acyliminoni-
trenes has been observed on irradiating some 5-phenyl-
oxadiazoles at λ ) 254 nm in methanol.7 Moreover, direct
irradiation of 11 at λ ) 313 nm in methanol essentially
gave the solvolysis product 12 (together with trace
amounts of 13) by an almost complete conversion of
starting material. This means that, although there is the
possibility for an intramolecular heterocyclization, the
predominant reaction of the presumed primarily formed
intermediate engages the nucleophilic solvent. On the
other hand, in the irradiation of 1a and 2a at λ ) 254
nm in methanol and in the presence of aliphatic amines,
(13) We had observed 4 that irradiation of 1a and 2a in the presence
of amines, besides the formation of the N-N bonded species, showed
the heterocyclization reaction into the quinazolin-4-one system to a
greater extent than that observed in methanol alone; this catalytic
effect by the amine reagent could now be explained on the basis of our
findings in the TEA-sensitized reactions.
(14) (a) Abraham, W.; Buchallik, M.; Zhu, Q. Q.; Schnabel, W. J .
Photochem. Photobiol., A 1993, 71, 119. (b) Clauss, K.-U.; Buck, K.;
Abraham, W. Tetrahedron 1995, 51, 7181.
(12) Nitrene chemistry in photochemical reactions is widely reported
in the literature. See, inter alia: (a) Iddon, B.; Meth-Cohn, O.; Scriven,
E. F. V.; Suschitzky, H.; Gallagher, P. T. Angew. Chem., Int. Ed. Engl.
1979, 18, 900. (b) Scriven, E. F. V. In Reactive Intermediates; Abra-
movitch, R. A., Ed.; Plenum Press: New York, 1982. (c) Azides and
Nitrenes; Scriven, E. F. V., Ed.; Academic Press: New York, 1984. (d)
Leyva, E.; Platz, M. S.; Persy, G.; Wirz, J . J . Am. Chem. Soc., 1986,
108, 3783.
(15) Auricchio, S.; Bini, A.; Pastormerlo, E.; Truscello, A. M.
Tetrahedron 1997, 53, 10911.
(16) Natale, N. R. Tetrahedron Lett. 1982, 5009.
(17) Herbranson, D. E.; Havley, M. D. J . Org. Chem. 1990, 55, 4297.
(18) (a) Shields, C. J .; Falvey, D. E.; Schuster, G. B.; Buchardt, O.;
Nielsen, P. E. J . Org. Chem. 1988, 53, 3501. (b) Zhu, Y.; Schuster, G.
B. J . Am. Chem. Soc. 1993, 115, 2190. (c) Murata, S.; Nakatsuji, R.;
Tomioka, H. J . Chem. Soc. 1995, 793.

Electron Transfer on 5-Aryl-1,2,4-oxadiazoles
J . Org. Chem., Vol. 64, No. 19, 1999 7031
Ta ble 3. En er gy Va lu es of th e Sin glet (Es) Sta te (As
Deter m in ed fr om Em ission Sp ectr a in Aceton itr ile),
Ca th od ic P ea k P oten tia ls (Ep ) (As Deter m in ed fr om
Cyclic Volta m m etr y), a n d ∆G° (Ca lcu la ted fr om th e
Reh m -Weller Equ a tion ) for DAC-, DAN-, TP H-, a n d
TEA-In d u ced P h otor ea ction s for Com p ou n d s 1a a n d 2a
Sch em e 3
∆G° (kJ /mol) 21
compd
Es (eV)
Ep (eV)
DAC
DAN
TPH
TEA
1a
2a
4.51
4.26
-1.66
-1.62
-81
-85
-29
-33
-55
-59
-183
-163
triethylamine returned starting material (60%) and gave
the quinazolin-4-one 4a (36%), while instead only trace
amounts of the corresponding reduction product 6a were
detected. Compounds 11 gave similar results.
Since the reaction is a photoinduced process, to explain
these findings, one can reasonably assume that the
excited oxadiazole really acts as an electron acceptor
counterpart of the ground electron donor reagent, pro-
ducing the forecast oxadiazole radical anion. Again, the
fate of the ring-cleaved species will depend on electronic
effects, as well as on the rate of subsequent processes.
Clearly, in the reduction pathway, triethylamine would
act as an electron-transfer reagent, while the proton
transfer will take place from TEA radical cation as well
from hydroxylic solvent. An attractiveness of this TEA-
induced photoreaction could be found in the possibility
of a generalized methodology for synthesis of variously
substituted quinazolin-4-ones. In this context, an ad-
ditional example was found in the photoreaction of
3-methyl-5-phenyl-1,2,4-oxadiazole (14) from which com-
pound 15 (63%) was easily obtained.
The whole investigation shows that in the sensitized
photochemistry of the 5-aryl-3-methoxy- (or 5-aryl-3-
phenyl-) 1,2,4-oxadiazoles the primary step of the reac-
tion should be an electron transfer, producing an oxadi-
azole radical anion as the key species from which the
breaking of the ring O-N bond takes place. Confirmation
of this hypothesis was found by calculating the ∆G° for
the electron transfer either from triethylamine to the
excited oxadiazole or from the sensitizer in its excited
state to the ground-state oxadiazole. The application of
the Rehm-Weller equation,20 using the cathodic peak
potentials (Ep) of the representative oxadiazoles 1a and
2a as determined by cyclic voltammetry experiments,
brings us to the conclusion that in both cases ∆G° < 0
(Table 3)21 so that the electron transfer may occur and
supporting the idea of a common intermediate being
formed. The electrochemical reduction of considered
compounds was not a reversible process,22 and this
observation agrees well with a primarily formed species
different extents depending on its structure, and then on
the rate of competing subsequent processes. Interestingly,
in the case of 3-methoxyoxadiazoles 1, reinforcement of
the acceptor characteristics of the 5-aryl-substituted
oxadiazoles enhances the photoconversion of starting
material and the reduction pathway as well (see Table
2). At first glance, the stabilization due to the methoxy
group and a decreasing efficiency of the heterocyclization
reaction (likely ascribable to a decreasing efficiency of
required back-electron transfer) could explain the results.
By contrast, when oxadiazoles 2 are considered, the
different stabilization of the corresponding open-chain
species (as well as different efficiency in the back-electron
transfer) could explain the difference in reactivity and
low significance of the reduction pathway. Further
investigations, however, appear necessary for a better
understanding of the role of each competing process
which follows the primary collapse of the presumed key
oxadiazole radical anion.
Ir r a d ia t ion s in t h e P r esen ce of Tr iet h yla m in e.
The above results suggested the possibility of creating
the oxadiazole radical anion via an electron-transfer
mechanism by direct irradiation of the oxadiazole system
from a ground-state electron donor reagent as tertiary
amines.19 Interestingly, irradiations of 3-methoxyoxadia-
zoles 1a -c (at λ ) 313 nm) in methanol and in the
presence of an excess of triethylamine gave a fast and,
in some cases, almost complete photoconversion of start-
ing material, producing both the expected quinazolinones
3a -c (which were isolated in about 50-60% yields) and
the reduction products 5a -c (in about 30% yields). In
its turn, the TEA-mediated irradiation of 7a gave 10a
(20%) and regioisomers 8a (52%) and 9a (24%). Again,
3-phenyl-substituted oxadiazoles showed a different re-
sponse. Typically, irradiation of 2a in the presence of
(20) (a) Rehm, D.; Weller, A. Isr. J . Chem. 1970, 8, 259. (b) Fox, M.
A.; Chanon, M. Photoinduced Electron Transfer. Part A; Elsevier:
Amsterdam, 1988.
(21) Calculation of the free energies for electron transfer: (a) Energy
values (eV) of the singlet excited state of DAC (4.11), DAN (3.16), and
TPH (3.63) came from ref 9. (b) The oxidation potentials (V vs
hydrogen) of DAC, DAN, TPH, and TEA were estimated to be (DAC),
1.61 (Mattes, S. L.; Farid, S. J . Chem. Soc., Chem. Commun. 1980,
457), (DAN) 1.20 (Bard, A. J .; Santhanam, K. S. V.; Maloy, J . T.;
Phelps, J .; Wheeler, L. O. Discuss. Faraday Soc. 1968, 167), (TPH)
1.40 (Mattes, S. L.; Farid, S. In Organic Photochemistry; Padwa, A.,
Ed.; Marcel Dekker: New York, 1983; Vol. 6), and (TEA) 0.95 (Mann,
C. K. Anal. Chem. 1964, 36, 2424).
(22) According to the proposed reaction pattern, an evaluation of
the eventual negative shift of standard redox potential E° with respect
to the Ep values has been done. (Nadjo, L.; Saveant, J . M. Electroanal.
Chem. Interfacial Electrochem. 1973, 48, 113. Nicholson, R. S.; Shain,
I. Anal. Chem. 1965, 37, 190), and the result does not affect the
previous consideration.
(19) See, e.g.: (a) Barltrop, J . A.; Coyle, J . D. Excited States in
Organic Chemistry; J ohn Wiley: London, 1975. (b) Turro, N. J . Modern
Molecular Photochemistry; Benjamin/Cummings: Menlo Park, CA,
1978.

7032 J . Org. Chem., Vol. 64, No. 19, 1999
Buscemi et al.
quinazolin-4-one (3a ), (0.1 g, 40%), mp 230-2 °C (from ethanol)
(lit.5,28 mp 230-2 °C).
quickly collapsing by an irreversible chemical reaction
(breaking of the ring O-N bond). Interestingly, apart
from significance in synthetic projects, all the results
open new approaches to mechanistic studies on the
photochemistry of O-N bond containing five-membered
heterocycles.
Ir r a d ia t ion of 3-Met h oxy-5-(4-m et h ylp h en yl)-1,2,4-
oxa d ia zole (1b) in th e P r esen ce of DAC. Irradiation of 1b
and chromatography returned starting material (0.14 g, 46%)
and gave O-methyl-N-(4-methylbenzoyl)isourea (5b) (0.025 g,
10%) and 2-methoxy-7-methylquinazolin-4-one (3b) (0.080 g,
32%). 5b: mp 70-2 °C (from benzene/light petroleum); IR
3460, 3275, 1620 cm-1; 1H NMR (DMSO-d6) δ 2.44 (s, 3H), 3.95
(s, 3H) 7.31 and 8.10 (2d, 4H), 8.51 and 8.85 (2s, 2H,
exchangeable with D2O); MS m/z 192 (M+). Anal. Calcd for
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. For instruments and general
procedures see our previous papers. IR spectra were recorded
from Nujol mulls. UV absorption spectra were recorded in
C
10H12N2O2: C, 62.49; H, 6.29; N, 14.57. Found: C, 62.40; H,
6.20; N, 14.50. 3b: mp 203-5 °C (from ethanol); IR 1670 cm-1
;
1H NMR (DMSO-d6) δ 2.49 (s, 3H), 4.01 (s, 3H), 7.22-7.98 (m,
1
methanol. H NMR spectra (250 MHz) were taken with TMS
3H), 12.27 (s, 1H); MS m/z 190 (M+). Anal. Calcd for
as internal standard. HPLC analyses were performed by using
a C-18 SIL-X-10 Perkin-Elmer column. Fluorescence emission
spectra were determined in methanol or acetonitrile, and
phosphorescence emissions (at 77 K) were determined in
acetonitrile. Energies of excited states are reported in Table
1. Flash chromatography was performed by using mixtures of
light petroleum (fraction boiling in the range of 40-60 °C) and
ethyl acetate in varying ratios. Diphenylacetylene, 9,10-
diphenylanthracene, triphenylene, triethylamine (99.9% grade),
and Bu4NBr were obtained from Aldrich Chemical Co.
Compounds 1a ,23 1b,24 1c,2 1d ,24 2a ,25 2b,26 7a ,24 and 1126
were prepared as reported. Compound 2c was prepared by
reacting benzamidoxime and 4-cyanobenzoyl chloride, follow-
ing the standard procedure.25 Compound 7b was prepared by
adopting the procedure reported for 1a . Absorption spectra of
all oxadiazoles 1a -d , 2a -c, and 7a ,b showed λmax values in
the range of 245-265 nm, but very low ꢀ values (in the range
of 1-100) at λ ) 313 nm. In turn, compound 11 had λmax at
281 nm and more significant ꢀ values at 300 and 313 nm
(10 000 and 500, respectively).
Photochemical reactions were carried out in anhydrous
methanol (from Romil Pure Chemicals) by using a Rayonet
RPR-100 photoreactor fitted with 16 lamps irradiating at λ )
313 or 365 nm (in 50 mL Pyrex vessels) and a merry-go-round
apparatus. On the basis of absorption spectra of oxadiazole
substrates, the conditions ensured that in each experiment the
sensitizer was the predominant absorbing species at the chosen
wavelength. In the case of analytical photoreactions, quantita-
tive determinations were accomplished by HPLC.
C
10H10N2O2: C, 63.15; H, 5.30; N, 14.73. Found: C, 63.20; H,
5.20; N, 14.80.
Ir r a d ia tion of 3-Meth oxy-5-(4-cya n op h en yl)-1,2,4-oxa -
d ia zole (1c) in th e P r esen ce of DAC. Irradiation of 1c and
chromatography returned starting material (0.045 g, 18%) and
gave O-methyl-N-(4-cyanobenzoyl)isourea (5c) (0.095 g, 38%)
and 2-methoxy-7-cyanoquinazolin-4-one (3c) (0.080 g, 33%).
5c: mp 161 °C (from ethanol); IR 3370, 3280, 2230, 1630 cm-1
;
1H NMR (DMSO-d6) δ 3.97 (s, 3H), 7.97-8.00 and 8.32-8.35
(2m, 4H), 8.63 and 8.96 (2s, 2H, exchangeable with D2O); MS
m/z 203 (M+). Anal. Calcd for C10H9N3O2: C, 59.11; H, 4.46;
N, 20.68. Found: C, 59.20; H, 4.50; N, 20.60. 3c: mp 249 °C
(from ethanol); IR 2200, 1690 cm-1; 1H NMR (DMSO-d6) δ 4.07
(s, 3H), 7.63-8.5 (m, 3H), 12.78 (s, 1H); MS m/z 201 (M+). Anal.
Calcd for C10H7N3O2: C, 59.70; H, 3.51; N, 20.89. Found: C,
59.60; H, 3.60; N, 20.80.
Ir r a d ia tion of 3-Meth oxy-5-(4-ch lor op h en yl)-1,2,4-oxa -
d ia zole (1d ) in th e P r esen ce of DAC. Irradiation of 1d and
chromatography returned starting material (0.09 g, 36%) and
gave O-methyl-N-(4-chlorobenzoyl)isourea (5d ) (0.055 g, 22%),
mp 86 °C (from ethanol) (lit.29 mp 86 °C) and then 2-methoxy-
7-chloroquinazolin-4-one (3d ) (0.100 g, 40%), mp 195 °C (from
ethanol): IR 1680 cm-1; 1H NMR δ (DMSO-d6) δ 4.04 (s, 3H),
7.42-8.09 (m, 3H), 12.55 (s, 1H); MS m/z 210 (M+). Anal. Calcd
for C9H7ClN2O2: C, 51.32; H, 3.35; N, 13.30. Found: C, 51.40;
H, 3.30; N, 13.40.
Ir r a d ia t ion of 3-Met h oxy-5-(3-m et h ylp h en yl)-1,2,4-
oxa d ia zole (7a ) in th e P r esen ce of DAC. Irradiation of 7a
and chromatography returned starting material (0.15 g, 60%)
and gave O-methyl-N-(3-methylbenzoyl)isourea (10a ) (0.01 g,
4%), 2-methoxy-8-methylquinazolin-4-one (8a ) (0.05 g, 20%),
and 2-methoxy-6-methylquinazolin-4-one (9a ) (0.04 g, 16%).
10a : mp 83-5 °C (from light petroleum); IR 3340, 3160, 1630
5-(4-Cya n op h en yl)-3-p h en yl-1,2,4-oxa d ia zole (2c): mp
1
161-2 °C (from ethanol); IR 2230 cm-1; H NMR (DMSO-d6)
δ 7.45-7.51 (m, 3H), 7.83 (d, 2H), 8.11-8.15 (m, 2H), 8.31 (d,
2H); MS m/z 247 (M+). Anal. Calcd for C15H9N3O: C, 72.87;
H, 3.67; N, 16.99. Found: C, 72.80; H, 3.70; N, 16.90.
5-(3-Ch lor oph en yl)-3-m eth oxy-1,2,4-oxadiazole (7b): mp
63-4 °C (from light petroleum); 1H NMR (CDCl3) δ 4.12 (s,
3H), 7.44-8.10 (m, 4H); MS m/z 210 (M+). Anal. Calcd for C9H7-
ClN2O2: C, 51.32; H, 3.35; N, 13.30. Found: C, 51.40; H, 3.40;
N, 13.40.
cm-1; H NMR (DMSO-d6) δ 2.36 (s, 3H),3.89 (s, 3H), 7.29-
1
7.96 (m, 4H), 8.49 and 8.80 (2s, 2H; exchangeable with D2O);
MS m/z 192 (M+). Anal. Calcd for C10H12N2O2: C, 62.49; H,
6.29; N, 14.57. Found: C, 62.40; H, 6.20; N, 14.50. 8a : mp
209-11 °C (from light petroleum/ethyl acetate); IR 3180, 1670
cm-1; H NMR (DMSO-d6) δ 2.46 (s, 3H), 3.97 (s, 3H), 7.19-
1
Gen er a l P r oced u r e for P h otoch em ica l Rea ction s in
th e P r esen ce of Dip h en yla cetylen e (DAC). To a sample
of the oxadiazole 1a -d , 2a -c, or 7a ,b (0.25 g, 1.0-1.4 mmol)
in methanol (45 mL; 140 mL in the cases of 1c and 2c) was
added a 5-fold excess of diphenylacetylene (5.0-7.0 mmol). The
solution was purged by bubbling nitrogen (10 min), and then
irradiated (at λ ) 313 nm) for 6 h (5 h for 1c). After removal
of the solvent, the residue was chromatographed.
7.86 (m, 3H), 12.24 (s, 1H); MS m/z 190 (M+). Anal. Calcd for
C
10H10N2O2: C, 63.15; H, 5.30; N, 14.73. Found: C, 63.10; H,
5.20; N, 14.80. 9a : mp 182-5 °C (from light petroleum/ethyl
acetate); IR 3160, 1670 cm-1; H NMR (DMSO-d6) δ 2.38 (s,
1
3H), 3.93 (s, 3H), 7.35-7.80 (m, 3H), 12.20 (s, 1H); MS m/z
190 (M+). Anal. Calcd for C10H10N2O2: C, 63.15; H, 5.30; N,
14.73. Found: C, 63.20; H, 5.40; N, 14.70.
Ir r a d ia tion of 3-Meth oxy-5-(3-ch lor op h en yl)-1,2,4-oxa -
d ia zole (7b) in th e P r esen ce of DAC. Irradiation of 7b and
chromatography returned starting material (0.055 g, 22%) and
gave O-methyl-N-(3-chlorobenzoyl)isourea (10b) (0.06 g, 24%),
2-methoxy-8-chloroquinazolin-4-one (8b) (0.06 g, 24%), and
then 2-methoxy-6-chloroquinazolin-4-one (9b) (0.075 g, 30%).
10b: mp 85-7 °C (from light petroleum); IR 3395, 3295, 1630
Ir r adiation of 3-Meth oxy-5-ph en yl-1,2,4-oxadiazole (1a)
in th e P r esen ce of DAC. Irradiation of 1a and chromatog-
raphy returned starting material (0.1 g, 40%) and gave
O-methyl-N-benzoylisourea (5a ) (0.045 g, 18%), mp 77 °C (from
benzene/light petroleum) (lit.27 mp 77 °C), and then 2-methoxy-
(23) (a) Katritzky, A. R.; Wallis, B.; Brownlee, R. T. C.; Topsom, R.
D. Tetrahedron 1965, 21, 1681. (b) Nash B. W.; Newberry R. A.; Pickles
R.; Warburton, W. K. J . Chem. Soc. C 1969, 2794.
(24) Neidlein, R.; Krull, H. Liebigs Ann. Chem. 1968, 716, 156.
(25) Sim Ooi, N.; Wilson, D. A. J . Chem. Soc., Perkin Trans. 2 1980,
1792.
1
cm-1; H NMR (DMSO-d6) δ 3.96 (s, 3H), 7.52-8.16 (m, 4H),
8.65 and 8.94 (2s, 2H, exchangeable with D2O); MS m/z 212
(M+). Anal. Calcd for C9H9ClN2O2: C, 50.84; H, 4.27; N, 13.17.
(26) Leandri, G.; Pallotti, M. Ann. Chim. (Rome) 1957, 47, 376.
(27) McKee, R. Am. J . Chem. Soc. 1901, 26, 209.
(28) Tennant, G.; Vaughan, K. J . Chem. Soc. (C) 1966, 2287.
(29) Rossi, E.; Spadi, R. Gazz. Chim. Ital. 1981, 111, 299.

Electron Transfer on 5-Aryl-1,2,4-oxadiazoles
J . Org. Chem., Vol. 64, No. 19, 1999 7033
Found: C, 51.90; H, 4.30; N, 13.10. 8b: mp 218-23 °C (from
Ir r a d ia tion of th e Oxa d ia zole 2a in th e P r esen ce of
TEA. Irradiation of 2a (6 h) returned starting material (0.15
g, 60%) and gave 4a (0.09 g, 36%) and trace amounts of 6a
(HPLC).
Ir r a d ia tion of th e Oxa d ia zole 7a in th e P r esen ce of
TEA. Irradiation of 7a (2 h) gave 10a (0.05 g, 20%), 8a (0.13
g, 52%), and 9a (0.06 g, 24%).
ethanol); IR 1685 cm-1 1H NMR (DMSO-d6) δ 4.06 (s, 3H),
;
7.34-8.05 (m, 3H), 12.62 (s, 1H); MS m/z 210 (M+). Anal. Calcd
for C9H7ClN2O2: C, 51.32; H, 3.35; N, 13.30. Found: C, 51.40;
H, 3.30; N, 13.20. 9b: mp 186-193 °C (from ethanol); IR 1675
cm-1; 1H NMR (DMSO-d6) δ: 4.01 (s, 3H), 7.38-8.00 (m, 3H),
12.50 (s, 1H); MS m/z 210 (M+). Anal. Calcd for C9H7ClN2O2:
C, 51.32; H, 3.35; N, 13.30. Found: C, 51.30; H, 3.40; N, 13.40.
Ir r a d ia tion of 3,5-Dip h en yl-1,2,4-oxa d ia zole (2a ) in th e
P r esen ce of DAC. Irradiation of 2a and chromatography
returned starting material (0.15 g, 60%) and gave trace
amounts of N-benzoylbenzamidine (6a ) (by HPLC with an
authentic sample5,30) and then 2-phenylquinazolin-4-one (4a )
(0.075 g, 30%), mp 232-6 °C (from ethanol) (lit.4,7a mp 233-4
°C).
Ir r a d ia tion of th e Oxa d ia zole 11. Irradiation of 11 (6 h)
in the presence of TEA and chromatography returned starting
material (0.135 g, 54%) and gave 2-phenyl-7-methoxyquinazo-
lin-4-one (13) (0.07 g, 28%): mp 197 °C (from ethanol); IR 3160,
1
1660 cm-1; H NMR (DMSO-d6) δ 3.97 (s, 3H), 7.14-8.25 (m,
8H), 12.49 (s, 1H); MS m/z 252 (M+). Anal. Calcd for
C
15H12N2O2: C, 71.42; H, 4.79; N, 11.10. Found: C, 71.50; H,
4.70; N, 11.20.
Ir r a d ia tion of 5-(4-Meth ylp h en yl)-3-p h en yl-1,2,4-oxa -
d ia zole (2b) in th e P r esen ce of DAC. Irradiation of 2b and
chromatography returned starting material (0.15 g, 60%) and
gave 7-methyl-2-phenylquinazolin-4-one (4b) (0.075 g, 30%):
Parallel irradiation (6 h) of 11 (0.12 g) in purged methanol
alone (40 mL) and chromatography returned a small amount
of starting material and gave 12 (0.085 g, 70%) and trace
amounts of 13. 12: mp 130 °C (from light petroleum); IR 3240,
1650 cm-1; 1H NMR (DMSO-d6) δ 3.91 (s, 3H), 3.98 (s,2H),7.12
(d, 2H), 7.46-7.63 (m, 5H), 8.04 (d, 2H), 10.07 (s, 1H); MS m/z
284 (M+). Anal. Calcd for C16H16N2O3: C, 67.59; H, 5.67; N,
9.85. Found: C, 67.50; H, 5.60; N, 9.90.
1
mp 208-10 °C (from ethanol); IR 3140, 1655 cm-1; H NMR
(DMSO-d6) δ 2.55 (s, 3H), 7.40-8.26 (m, 8H), 12.52 (s, 1H);
MS m/z 236 (M+). Anal. Calcd for C15H12N2O: C, 76.25; H, 5.12;
N, 11.86. Found: C, 76.30; H, 5.20; N, 12.90.
Ir r a d ia tion of 5-(4-Cya n op h en yl)-3-p h en yl-1,2,4-oxa -
d ia zole (2c) in th e P r esen ce of DAC. Irradiation of 2c and
chromatography returned starting material (0.16 g, 64%) and
gave 7-cyano-2-phenylquinazolin-4-one (4c) (0.085 g, 34%): mp
302-5 °C (from ethanol); 1H NMR (DMSO-d6) δ 7.61-8.60 (m,
8H), 12.97 (s, 1H); MS m/z (247 M+). Anal. Calcd for
Ir r a d ia tion of th e Oxa d ia zole 14 in th e P r esen ce of
TEA. Irradiation of 1425 (2 h) and chromatography gave
2-methylquinazolin-4-one (15) (0.16 g, 63%), mp 236-238 °C
(from ethanol) (lit.9,31 mp 236-238 °C), and some amount of
benzamide.
An a lytica l P h otor ea ction s. (a) To a sample of the oxa-
diazole (0.06 mmol) in methanol (10 mL) was added diphenyl-
acetylene (0.3 mmol). The solution was purged by bubbling
nitrogen (5 min) and then irradiated at λ ) 313 nm for 2 h.
(b) A sample (10 mL) containing the oxadiazole (0.006 mmol)
and diphenylanthracene (0.015 mmol) was purged and then
irradiated (at λ ) 365 nm) for 45 min. (c) A sample (10 mL)
containing the oxadiazole (0.011 mmol) and triphenylene
(0.022 mmol) was purged and then irradiated (at λ ) 313 nm)
for 45 min. Irradiation times were chosen to have clear-cut
HPLC response. The resulting photolyzates were analyzed
quantitatively by HPLC. Compositions (%) of the photoreaction
mixtures were reported in Table 2. Obviously, no significant
comparison can be made between the DAC-sensitized photo-
reactions on one hand, and DAN- or TPH-sensitized photore-
actions, on the other.
Cyclic Volta m m etr y Exp er im en ts. Cyclic voltammetry
experiments were performed by using 0.1 M Bu4NBr in
acetonitrile as a system solvent supporting electrolyte (SSE)
in an undivided glass cell equipped with a graphite disk
working electrode (7 mm2), platinum counter electrode, and
saturated calomel electrode (SCE) as reference electrode. The
modulation of the working potential was tuned by an AMEL
System 5000 potentiostat controlled through a PC. In each
experiment a 5 mM concentration of the selected oxadiazole
was dissolved in 30 mL of the SSE helium saturated, and a
set of triangular wave potential modulations were carried out
with different scan rates in the range 10-1000 mV s-1. The
resulting cathodic peak potentials (Ep) (vs hydrogen) are
reported in Table 3.
C
15H9N3O: C, 72.87; H, 3.67; N, 16.99. Found: C, 72.80; H,
3.60; N, 16.90.
Ir r a d ia tion of th e Oxa d ia zole 1a in th e P r esen ce of
Dip h en yla n th r a cen e. To a sample of the oxadiazole 1a (0.25
g, 1.4 mmol) in methanol (250 mL) was added diphenylan-
thracene (0.12 g, 0.4 mmol). The solution was purged by
bubbling nitrogen (10 min) and then irradiated (at λ ) 365
nm) for 6 h. After removal of the solvent, chromatography of
the residue returned starting material (0.045 g, 18%) and gave
5a (0.03 g, 12%) and 3a (0.13 g, 52%).
Ir r a d ia tion of th e Oxa d ia zole 2a in th e P r esen ce of
Dip h en yla n th r a cen e. Similarly, after irradiation (6h) of 2a
(0.25 g, 1.1 mmol) in methanol (250 mL) and diphenylan-
thracene (0.12 g, 0.4 mmol), subsequent chromatography
returned starting material (0.075 g, 30%) and gave 4a (0.125
g, 50%).
Gen er a l P r oced u r e for P h otoch em ica l Rea ction s in
th e P r esen ce of Tr ieth yla m in e (TEA). To a solution of the
oxadiazole 1a -c, 2a , 7a , 11, or 14 (0.25 g, 1.0-1.4 mmol) in
methanol (90 mL; 140 mL in the case of 1c) purged by bubbling
nitrogen (10 min) was added an excess of triethylamine (5 mL),
and then the mixture was irradiated (at λ ) 313 nm) for the
time indicated. After removal of the solvent, the residue was
chromatographed.
Ir r a d ia tion of th e Oxa d ia zole 1a in th e P r esen ce of
TEA. Irradiation of 1a (2 h) gave 5a (0.075 g, 30%) and 3a
(0.125 g, 50%).
Ir r a d ia tion of th e Oxa d ia zole 1b in th e P r esen ce of
TEA. Irradiation of 1b (2 h) gave 5b (0.075 g, 30%) and 3b
(0.15 g, 60%).
Ir r a d ia tion of th e Oxa d ia zole 1c in th e P r esen ce of
TEA. Irradiation of 1c (1 h) gave 5c (0.075 g, 30%), 3c (0.12
g, 50%), and some amount of byproducts.
Ack n ow led gm en t . Financial support by CNR
(Roma) and MURST (Roma) is gratefully acknowledged.
J O990298F
(30) Palazzo, G.; Strani, G.; Tavella, M. Gazz. Chim. Ital. 1961, 91,
1085.
(31) Bogert, M. T.; Gotthelf, A. H. J . Am. Chem. Soc. 1900, 22, 512.