Photoinduced molecular rearrangements. The photochemistry of some 1,2,4-oxadiazoles in the presence of nitrogen nucleophiles. Formation of 1,2,4-triazoles, indazoles, and benzimidazoles

Article abstract of DOI:10.1021/jo960765i

The photochemistry of some 3,5-disubstituted 1,2,4-oxadiazoles in the presence of nitrogen nucleophiles [external, such as added amines or hydrazines, or internal, such as an o-aminophenyl moiety at C(3) of the oxadiazole ring] has been investigated. In the irradiation of 5-amino-(or 5-N-substituted amino) 3-phenyl-1,2,4-oxadiazoles in the presence of aliphatic primary amines (or ammonia), photolytic species arising from heterolytic cleavage of the ring O-N bond capture the nucleophilic reagent to give open-chain intermediates, which develop into 1,2,4-triazolin-5-ones. Similarly, irradiations of 3,5-diphenyl-, 3-methoxy-5-phenyl-, and 5-methyl-3-phenyl-1,2,4-oxadiazoles gave 1,2,4-triazoles. In the same context, irradiations of representative substrates in the presence of hydrazines have been also investigated. In the irradiation of 3-(o-aminophenyl)-5-methyl-, 3-[o-(methylamino)phenyl]-5-methyl-, and 3-(o-aminophenyl)-5-phenyl-1,2,4-oxadiazoles, concomitant formation of indazoles and benzimidazoles, presumably arising from a common photolytic species, has been observed. Some mechanistic aspects have been considered, and possible applications in synthesis have been pointed out.

Full text of DOI:10.1021/jo960765i

J . Org. Chem. 1996, 61, 8397-8401
8397
P h otoin d u ced Molecu la r Rea r r a n gem en ts. Th e P h otoch em istr y of
Som e 1,2,4-Oxa d ia zoles in th e P r esen ce of Nitr ogen Nu cleop h iles.
F or m a tion of 1,2,4-Tr ia zoles, In d a zoles, a n d Ben zim id a zoles
Silvestre Buscemi and Nicolo` Vivona*
Dipartimento di Chimica Organica, Universita` di Palermo, Via Archirafi 20, 90123 Palermo, Italy
Tullio Caronna
Dipartimento di Chimica, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy
Received April 26, 1996X
The photochemistry of some 3,5-disubstituted 1,2,4-oxadiazoles in the presence of nitrogen
nucleophiles [external, such as added amines or hydrazines, or internal, such as an o-aminophenyl
moiety at C(3) of the oxadiazole ring] has been investigated. In the irradiation of 5-amino-(or 5-N-
substituted amino) 3-phenyl-1,2,4-oxadiazoles in the presence of aliphatic primary amines (or
ammonia), photolytic species arising from heterolytic cleavage of the ring O-N bond capture the
nucleophilic reagent to give open-chain intermediates, which develop into 1,2,4-triazolin-5-ones.
Similarly, irradiations of 3,5-diphenyl-, 3-methoxy-5-phenyl-, and 5-methyl-3-phenyl-1,2,4-oxadia-
zoles gave 1,2,4-triazoles. In the same context, irradiations of representative substrates in the
presence of hydrazines have been also investigated. In the irradiation of 3-(o-aminophenyl)-5-
methyl-, 3-[o-(methylamino)phenyl]-5-methyl-, and 3-(o-aminophenyl)-5-phenyl-1,2,4-oxadiazoles,
concomitant formation of indazoles and benzimidazoles, presumably arising from a common
photolytic species, has been observed. Some mechanistic aspects have been considered, and possible
applications in synthesis have been pointed out.
In tr od u ction
a synthetic point of view, and to get more insight in the
photochemistry of 1,2,4-oxadiazoles, we now planned to
study irradiations of variously substituted substrates in
the presence of nitrogen nucleophiles. This would have
allowed us to extend the understanding of the photolysis
of these systems and to open up some novel synthetic
transformations. For the study we have at first consid-
ered irradiations of oxadiazoles 1-3 and 13-15 in the
presence of an external nucleophile such as an added
amine or hydrazine. Significantly, compounds 1-3 are
characterized by a substituent at C(5) having a conjuga-
tive electronic effect in one hand and a possible leaving-
group ability in the other. Furthermore, we have con-
sidered compounds 27-29 containing an o-aminophenyl
group at C(3) of the oxadiazole ring: interestingly, this
group had to be considered an internal nitrogen nucleo-
phile, which would have been well arranged for a het-
erocyclization reaction involving any ring-photolytic spe-
cies. In their turn, oxadiazoles 27, 28, and 29 are
known12 to rearrange thermally into 3-(acylamino)inda-
zoles 32, 33, and 34, respectively, following the Boulton/
Katritzky rearrangement pattern.13 In particular, owing
to the low nucleophilic character of the attacking nitro-
gen, these rearrangements take place under severe
conditions.12
The photochemistry of 3,5-disubstituted 1,2,4-oxadia-
zoles in methanol is characterized by photolysis of the
ring O-N bond into open-chain species which develop
into final products depending on the nature and position
of substituents.1-8 A quite generalizable behavior was
recognized in the formation of compounds arising from
a reaction of the electrophilic nitrogen of the photolytic
species with the nucleophilic solvent.1b,3 In some cases,
nitrene-type intermediates can even isomerize into a
carbodiimide which the solvent will then capture.3,8
Moreover, in the irradiation of 5-aryl substituted oxa-
diazoles, the formation of quinazolinones has been re-
ported and explained by a heterocyclization reaction
involving the electrophilic nitrogen of the photolytic
species and the C(5)-aryl moiety.1b,3,7 Furthermore, pho-
toinduced rearrangements of oxadiazoles containing cer-
tain three-(four-)atom side-chains linked at C(3) have
been also recognized.4-6
In pursuing our interest8-11 in the photochemistry of
five-membered heterocycles both from a mechanistic and
X Abstract published in Advance ACS Abstracts, November 1, 1996.
(1) (a) Newman, H. Tetrahedron Lett. 1968, 2417. (b) Ibid. 1968,
2421.
(2) Buscemi, S.; Cicero, M. G.; Vivona, N.; Caronna, T. J . Chem.
Soc., Perkin Trans. 1 1988, 1313.
(3) Buscemi, S.; Cicero, M. G.; Vivona, N.; Caronna, T. J . Heterocycl.
Chem. 1988, 25, 931.
(4) Buscemi, S.; Vivona, N. J . Heterocycl. Chem. 1988, 25, 1551.
(5) Buscemi, S.; Cusmano, G.; Gruttadauria, M. J . Heterocycl. Chem.
1990, 27, 861.
(6) (a) Buscemi, S.; Vivona, N. Heterocycles 1989, 29, 737. (b)
Buscemi, S.; Macaluso, G.; Vivona, N. Heterocycles 1989, 29, 1301.
(7) Buscemi, S.; Vivona, N. J . Chem. Soc., Perkin Trans. 2 1991,
187.
(8) Vivona, N.; Buscemi, S. Heterocycles 1995, 41, 2095.
(9) Buscemi, S.; Frenna, V.; Vivona, N.; Caronna, T. Heterocycles
1992, 34, 2313.
(10) Buscemi, S.; Vivona, N.; Caronna, T. J . Org. Chem. 1995, 60,
4096.
Resu lts a n d Discu ssion
Ir r a d ia t ion s of 5-Am in o-(or 5-N-su b st it u t ed
a m in o)-3-p h en yl-1,2,4-oxa d ia zoles. We have consid-
ered irradiations (at λ ) 254 nm in methanol) in the
(12) (a) Vivona, N.; Cusmano, G.; Macaluso, G.; Frenna, V.; Ruccia,
M. J . Heterocycl. Chem. 1979, 16, 783. (b) Korbonits, D.; Kanzel-
Szvoboda, I.; Horvath, K. J . Chem. Soc., Perkin Trans. 1 1982, 759.
(13) (a) Boulton, A. J .; Katritzky, A. R.; Hamid, A. M. J . Chem. Soc.
C 1967, 2005. (b) Boulton, A. J . Lect. Heterocycl. Chem., 1974, 2, 45.
(c) Ruccia, M.; Vivona, N.; Spinelli, D. Adv. Heterocycl. Chem. 1981,
29, 141. (d) Vivona, N.; Buscemi, S.; Frenna, V.; Cusmano, G. Adv.
Heterocycl. Chem. 1993, 56, 49.
(11) Buscemi, S.; Vivona, N.; Caronna, T. Synthesis 1995, 917.
S0022-3263(96)00765-7 CCC: $12.00 © 1996 American Chemical Society

8398 J . Org. Chem., Vol. 61, No. 24, 1996
Buscemi et al.
Sch em e 1
Sch em e 2
presence of primary aliphatic amines such as methyl-
amine. In some instances, for demonstrative purposes,
methanolic ammonia, propylamine, or butylamine was
also employed. Moreover, irradiations in the presence
of hydrazine have been representatively tested. In any
case, by means of parallel reactions, we have ascertained
that starting substrates were inert under thermal ami-
nolysis or ammonolysis conditions.
To obtain 1-amino-1,2,4-triazolin-5-ones, we have then
irradiated the representative oxadiazole 1 in the presence
of hydrazine monohydrate. As expected, the photoreac-
tion gave the 1-amino compound 9, but fair yields were
observed because, inter alia, some amounts of the pho-
tochemically deaminated compound 5 were also formed.
This photoreactivity, however, did not appear applicable
to the use of alkylhydrazines. For example, irradiation
of 1 in the presence of N,N-dimethylhydrazine failed to
give the expected 1-(N,N-dimethylamino)triazolin-5-one
derivative; surprisingly, this photoreaction mainly gave
the carbamoylbenzamidine 12, as a result of a redox
reaction. Although abstraction of hydrogens by the ring-
photolytic species is documented in the photochemistry
of 1,2,4-oxadiazoles,1,8 further investigations regarding
the role of the hydrogen-donor reagent appear to be
necessary. In the present case, the reduction may
proceed by the usual intermediate [10; R ) N(Me)2] which
will collapse by electron flow from nitrogen of the
hydrazine moiety into the imine nitrogen atom,14 rather
than by cyclization into the triazole ring.
Ir r a d ia tion s of 3-P h en yl-(or 3-m eth oxy)-5-su bsti-
tu ted -1,2,4-oxa d ia zoles. Irradiation of compounds 13,
14, and 15 in the presence of methylamine gave triazoles
17, 18, and 19, respectively, through intermediates 22
(Scheme 2). Accordingly, irradiation of 13 in the presence
of dimethylamine gave compound 23. Similarly, irradia-
tion of 13 in the presence of methanolic ammonia or
hydrazine gave 20 or 21, respectively.
On the whole, irradiations of oxadiazoles 13-16 pro-
ceeded with lower conversion of starting material, and
then lower yields of final triazoles were found. On the
other hand, increasing irradiation time did not signifi-
cantly increase yields of triazoles (after prolonged ir-
Irradiation of oxadiazoles 1-3 in the presence of an
excess of ethanolic methylamine produced the 1-methyl
substituted 1,2,4-triazolin-5-one 6. Similarly, when ir-
radiated in the presence of methanolic ammonia, propyl-
amine, or butylamine, compound 1 gave the unsubsti-
tuted triazole 5 or the 1-alkyl substituted compounds 7
and 8, respectively. Because of the occurrence of minor
photoreactions and/or secondary processes, yields of
isolated products were not improved more than 60%.
Significantly, in the irradiation of the oxadiazole 1 in the
presence of methanolic ammonia, some amounts of the
carbamoylbenzamidine 12 have been also detected (see
later on). Furthermore, parallel irradiations of the
representative oxadiazole 1 in methanol with and without
methylamine showed (by HPLC; at low conversion of
starting material) that the rate of disappearence of
starting material was not affected by the presence of the
amine.
These results may be accommodated by assuming a
reaction of the photolytic species 4 with the actual
nucleophile to give open-chain intermediates 10 (Scheme
1). Subsequent selective cyclization of 10 into 1,2,4-
triazolin-5-ones will then imply elimination of the YH
moiety. Accordingly, irradiation of 1 in the presence of
dimethylamine gave 11. The formation of an N-N bond
in the reaction between 4 and an external nitrogen-
nucleophile appears noteworthy, especially when mecha-
nistic and synthetic aspects of these photoreactions are
considered. By contrast, internal N-N bond-formation
by direct cyclization of (4; Y ) NH2 or NHMe) into the
triazole nucleus does not occur.3
(14) Mure, M.; Nii, K.; Inoue, T.; Itoh, S.; Ohshiro, Y. J . Chem. Soc.,
Perkin Trans. 2 1990, 315.

Photoinduced Molecular Rearrangements
J . Org. Chem., Vol. 61, No. 24, 1996 8399
Sch em e 3
radiations, they did not exceed values of about 30%)
because secondary processes also take place. In the
irradiation of 5-phenyl substituted oxadiazoles 13 and
14 we also isolated some amounts of the quinazolin-4-
ones 24 and 25, respectively, which originate from a
heterocyclization reaction involving the C(5)-phenyl ring.
(Further investigations are necessary to clarify the role
of methylamine, if any, in this concomitant photoreac-
tion). In addition, in the irradiation of the oxadiazole
13 in the presence of methylamine, the N-[(methylami-
no)carbonyl]-N′-phenylbenzamidine 2615 was also found.
Furthermore, irradiation of 13 in the presence of N,N-
dimethylhydrazine mainly gave the N-benzoylbenzami-
dine as a reduction product.
The formation of 1,2,4-triazoles from 1,2,4-oxadiazoles
deserves some comments. It is well known16 that 3,5-
disubstituted 1,2,4-oxadiazoles show remarkable stability
toward hydrolytic reagents [only for oxadiazoles mono-
substituted at C(5) or at C(3) is this inertness lost]. Our
photochemical results, at least formally, could represent
aminolysis (or ammonolysis) at the ring O-N bond,
allowing the synthesis of 1,2,4-triazoles. In this context,
if one considers the easy workup procedure and the high
conversion of starting material, the photoinduced ami-
nolysis of 5-amino-3-aryl-1,2,4-oxadiazoles could be suc-
cessfully exploited for the synthesis of target 1-alkyl-3-
aryl-1,2,4-triazolin-5-ones. On the other hand, despite
the low yields of 1-alkyl-3,5-disubstituted 1,2,4-triazoles,
this design in synthesis could be of some interest in view
of the fact that many 1-substituted 1,2,4-triazoles have
found use for their biological activity.17
Ir r a d ia t ion s of 3-(o-Am in op h en yl)- or 3-[o-(Me-
th yla m in o)p h en yl]- 5-su bstitu ted 1,2,4-Oxa d ia zoles.
When irradiated at λ ) 310 nm in methanol, compounds
27 and 28 gave complete conversion of starting material
in a rather clean and very fast photoreaction, which
produces mixtures of 3-(acetylamino)indazoles [32 (25%)
and 33 (30%)] and 2-(acetylamino)benzimidazoles [35
(75%) and 36 (70%)], respectively. Irradiation at λ ) 254
nm produced similar results; however, at this wavelength
photoreactions did not follow a clean course, and lower
yields have been observed because of the subsequent
photoreactivity of final products. Both indazoles and
benzimidazoles must be considered primary photo-
products: in fact, separate irradiations (at λ ) 310 nm)
of 32 and 35 (or 33 and 36) did not show any photo-
chemical interconversion (Scheme 3).
studied, quenching and sensitization experiments gave
negative results, showing that singlet excited states are
involved.
The concomitant formation of indazoles and benzimi-
dazoles could arise from a common photolytic species 30.
In one hand, this will develop into indazoles through the
N-N bond closure, that is, in a manner similar to that
observed in the irradiation of previous substrates in the
presence of an added amine. In the other, the photolytic
species will develop into the carbodiimide 31, a reason-
able precursor of the benzimidazole nucleus. The low
nucleophilic character of the attacking amino group
appears unfavorable to the indazole ring-closure; by
contrast, the migration of the phenyl moiety into 31 could
result in an o-amino-assisted process. Taking into ac-
count that 1,2,4-oxadiazoles can be considered masked
O-acylamidoximes, we see that photoinduced formation
of the benzimidazole ring from 3-(o-aminophenyl)oxadia-
zoles parallels the thermally-induced transformation (in
neutral medium) of o-amino- (or ortho-N-substituted-
amino) O-acylbenzamidoximes into 2-aminobenzimida-
zoles.18 Interestingly, when applied to various 3-(2-
aminoheteroaryl)-5-substituted 1,2,4-oxadiazoles, the
observed rearrangement could be fruitfully exploited for
the synthesis of target benzimidazole hetero analogues.
To gain information on the photoreaction, we irradiated
representative 27 in the presence of methylamine as an
external nitrogen nucleophile. Taking into account ir-
radiations of previous substrates in the presence of
amines, we could have expected to some extent a com-
petitive involvement of the added methylamine. How-
ever, parallel irradiations (at λ ) 310 nm) of the
oxadiazole 27 in methanol, with and without methy-
lamine, did not show any difference both in the rate of
the conversion of starting material and in the composition
of the final photolysate. Compounds 28 (at λ ) 310 nm)
and 29 (at λ ) 254 nm) behaved similarly. Although an
intramolecular heterocyclization should be easier than
an intermolecular reaction involving the external reagent,
the observed results suggest that the o-aminophenyl
Differently from what was observed for compounds 27
and 28, irradiation of the 5-phenyl substituted oxadiazole
29 at λ ) 310 nm proceeded with lower conversion of
starting material. Better results have been, however,
obtained on irradiating 29 at λ ) 254 nm: at this
wavelength, the conversion was complete and only the
expected mixture of the indazole 34 (45%) and benzimi-
dazole 37 (55%) resulted. Moreover, in all cases we
(15) A tautomer of 26 could be also considered. Although we have
no mechanistic evidence, tentatively the formation of compound 26
(which is independent from the presence of products 17 or 24) could
be explained by assuming the N-benzoyl-N′-phenylcarbodiimide as a
reasonable photolytic intermediate. However, whether the migration
of the phenyl moiety of the benzoyl group at the carbodiimidic carbon
atom will precede or follow the involvement of methylamine remains
questionable.
(16) (a) Clapp, L. B. Adv. Heterocycl. Chem. 1976, 20, 65. (b) Clapp,
L. B. 1,2,3- and 1,2,4-Oxadiazoles. Comprehensive Heterocyclic Chem-
istry; Katritzky, A. R.; Rees, C. W., Eds; Pergamon Press: Oxford, 1984;
Vol. 6, p 365.
(18) (a) Korbonits, D.; Kolonits, P. J . Chem. Res. (M) 1988, 1652;
(S) 1988, 209. (b) Korbonits, D.; Kanzel-Szvoboda, I.; Gonczi, C.; Simon,
K.; Kolonits, P. Chem. Ber. 1989, 122, 1107.
(17) Balasubramanian, M.; Keay, J . G.; Scriven, E. F. V. Heterocycles
1994, 37, 1951.

8400 J . Org. Chem., Vol. 61, No. 24, 1996
Buscemi et al.
Ta ble 1. En er gies Va lu es (k J /m ol) of Sin glet (Es) a n d
Tr ip let (Et) Sta te for Com p ou n d s 1-3, 13-15, a n d 27-29
As Deter m in ed fr om Em ission Sp ectr a
mL)] or hydrazine monohydrate (5 mL). The solution was
apportioned into two quartz tubes and then irradiated for the
time indicated. After removal of the solvent, the residue was
suitably worked-up as below. Minor components were dis-
carded.
Ir r a d ia t ion of Oxa d ia zoles 1-3 in t h e P r esen ce of
Meth yla m in e. Irradiation for 1.5 h and chromatography
returned starting material (10%) and gave 1-m eth yl-3-p h en -
yl-1,2,4-tr ia zolin -5-on e (6) (60%), mp 218-219 °C (lit.24 mp
218-219 °C).
compd
Es
Et
1
2
3
13
14
15
27
28
29
435
427
435
405
412
427
332
323
315
299
299
315
281
291
295
285
278
278
Ir r a d ia tion of th e Oxa d ia zole 1 in th e P r esen ce of
Am m on ia , P r op yla m in e, a n d Bu tyla m in e. Irradiation of
1 (0.5 g) in the presence of methanolic ammonia for 1.5 h,
followed by workup of the residue with the minimum of
methanol and filtration, gave the 3-p h en yl-1,2,4-tr ia zolin -
5-on e (5) (0.25 g), mp 325-330 °C (lit.24 mp 330-332 °C).
Chromatography of the mother liquor, besides starting mate-
rial (0.05 g; 10%) and additional 5 (0.05 g; total yield 60%),
gave the N-ca r ba m oylben za m id in e 12 (0.05 g; 10%), mp
132-4 °C (from benzene-ethyl acetate) (lit.25 mp 135-6 °C),
compared with a sample prepared by hydrogenolysis of 1.25
Similarly, irradiation of 1 (0.5 g) in the presence of propyl-
amine for 1.5 h and chromatography gave the 3-p h en yl-1-
p r op yl-1,2,4-tr ia zolin -5-on e (7) (0.38 g; 60%), mp 176-178
°C (from aqueous ethanol); IR (KBr pellets) 2680-3150, 1680
chromophore should be involved in an excited state
allowing some concertedness in the O-N bond cleavage
on one hand, and N-N bond formation (to indazoles) or
phenyl migration and ring-closure (to benzimidazoles) on
the other.
As last comment, these investigations show that in the
photochemistry of 1,2,4-oxadiazoles the first step of the
reaction should be considered the breaking of the ring
O-N bond; the fate of the intermediate will then depend
on the presence of a nucleophile, internal or external to
the reacting molecule, as well as from the possibility of
a subsequent heterocyclization reaction. This last be-
havior adds to the attractiveness of the photochemisty
of O-N bond-containing azoles the opportunity of a
number of applications in heterocyclic synthesis.
1
cm-1; H-NMR (DMSO-d6) δ 0.88 (t, 3H, J ) 7.0 Hz), 1.63-
1.78 (m, 2H), 3.67 (t, 2H, J ) 7.0 Hz), 7.42-7.81 (m, 5H), 12.19
(s, 1H); MS m/z 203 (M+). Anal. Calcd for C11H13N3O: C,
65.01; H, 6.45; N, 20.67. Found: C, 65.20; H, 6.60; N, 20.60.
Irradiation of 1 (0.5 g) in the presence of butylamine for 1.5
h gave 1-bu tyl-3-p h en yl-1,2,4-tr ia zolin -5-on e (8) (0.4 g;
60%), mp 146-148 °C (from aqueous ethanol); IR (KBr pellets)
1
2700-3150, 1685 cm-1; H-NMR (DMSO-d6) δ 0.95 (t, 3H, J
Exp er im en ta l Section
) 7.0 Hz), 1.28-1.43 and 1.66-1.77 (2 m, 4H), 3.76 (t, 2H, J
) 7.0 Hz), 7.50-8.04 (m, 5H), 12.25 (s, 1H); MS m/z : 217
(M+). Anal. Calcd for C12H15N3O C, 66.34; H, 6.96; N, 19.34.
Found: C, 66.50; H, 6.80; N, 19.50.
Ma ter ia ls a n d Meth od s. For instruments and general
procedures see our previous papers.9,11 IR spectra were
recorded from Nujol mulls unless otherwise specified. 1H NMR
spectra (250 MHz) were taken with TMS as internal standard.
HPLC analyses were performed by using a C-18 SIL-X-10
Perkin-Elmer column. Fluorescence and phosphorescence
emissions were determined on a J ASCO FP 770 equipped with
phosphorimeter in frozen glass (ethanol, pentane, ethyl ether
in a 2:5:5 ratio). Flash chromatography was performed by
using ethyl acetate or mixtures of light petroleum (fraction
boiling in the range of 40-60 °C) and ethyl acetate in varying
ratios. Ethanolic (33%) methylamine and dimethylamine,
hydrazine monohydrate, N,N-dimethylhydrazine, propylamine,
and butylamine were obtained from Aldrich Chemical Co.
Saturated methanolic ammonia was freshily prepared.
Compounds 1,19 2,20 3,20 13,21 1422 , 1521, 2723 , 28,12a and
2912b were prepared as reported. All these oxadiazole deriva-
tives except one (29) showed similar photophysical behavior
with a strong fluorescence emission and weaker phosphores-
cence. Values of singlet (Es) and triplet (Et) energies (kJ /mol)
determined from emission spectra are given in the Table 1.
Photochemical reactions were carried out in anhydrous metha-
nol (from Aldrich), by using a Rayonet RPR-100 photoreactor
fitted with 16 lamps irradiating at λ ) 254 nm (in quartz
vessels) or at λ ) 313 nm (in Pyrex vessels) and a merry-go-
round apparatus. In the case of analytical photoreactions,
quantitative determinations were accomplished by HPLC.
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 Nu cleop h iles. To a sample of the oxadia-
zole 1-3 or 13-15 (0.5 g; 2.0-3.0 mmol) in methanol (90 mL)
was added a large excess of the appropriate amine [namely:
methanolic ammonia (20 mL), ethanolic methylamine or
dimethylamine (10 mL), propylamine (5 mL), butylamine (6
Ir r a d ia t ion of t h e Oxa d ia zole 1 in t h e P r esen ce of
Dim eth yla m in e. Irradiation of 1 (0.5 g) for 1.5 h, followed
by workup with the minimum of ethyl acetate and filtration,
gave R-(N,N-d im et h ylh yd r a zon o)-N-ca r b a m oylb en zyl-
a m in e (11) (0.4 g; 63%), mp 163 °C (from ethyl acetate); IR
1
3420, 3210, 3140, 1705 cm-1; H-NMR (DMSO-d6) δ 2.52 (s,
6H), 6.49 (s, 2H), 7.35-7.47 (m, 5H), 8.63 (s, 1H); MS m/z 206
(M+). Anal. Calcd for C10H14N4O: C, 58.24; H, 6.84; N, 27.16.
Found: C, 58.40; H, 6.70; N, 27.30.
Ir r a d ia tion of th e Oxa d ia zole 1 in th e P r esen ce of
Hyd r a zin e or N,N-Dim eth ylh yd r a zin e. Irradiation of 1
(0.5 g) in the presence of hydrazine for 1.5 h and chromatog-
raphy, besides starting material (0.05 g; 10%), gave compound
5 (0.1 g; 20%) and then 1-a m in o-3-p h en yl-1,2,4-tr ia zolin -
5-on e (9) (0.2 g; 37%), mp 235-240 °C (lit.26 mp 235-238 °C).
Irradiation of 1 (0.5 g) in the presence of N,N-dimethylhydra-
zine (5 mL) for 1.5 h and chromatography, besides starting
material (0.05 g; 10%) and minor components which were
discarded, gave 12 (0.3 g; 60%).
Ir r a d ia tion of th e Oxa d ia zole 13 in th e P r esen ce of
Meth yla m in e, Meth a n olic Am m on ia , Dim eth yla m in e,
Hyd r a zin e, a n d N,N-d im eth ylh yd r a zin e. Irradiation of 13
(0.5 g) in the presence of methylamine for 2 h and chroma-
tography gave starting material (0.3 g; 60%), 1-m eth yl-3,5-
d ip h en yl-1,2,4-tr ia zole (17) (0.1 g; 20%), mp 82 °C (from
aqueous ethanol) (lit.27 mp 81,5-82,5), and then traces of
2-p h en ylqu in a zolin -4-on e (24) mp 235-237 °C (lit.1 mp
235-237 °C). Irradiation for 6 h and chromatography, besides
starting material (0.05 g; 10%), gave 24 (0.08 g; 16%), 26 (0.06
g; 10%), and 17 (0.15 g; 30%). N-(Meth yla m in oca r bon yl)-
N′-p h en ylben za m id in e (26) (or/and its tautomer): mp 160-
164 °C (from benzene-light petroleum); IR 3210, 3100, 1680,
(19) Eloy, F.; Lenaers, R. Helv. Chim. Acta 1966, 49, 1430.
(20) Selim, M.; Selim, M. Bull. Soc. Chim. Fr. 1967, 1219.
(21) Sim Ooi, N.; Wilson, D. A. J . Chem. Soc., Perkin Trans. 2 1980,
1792.
(22) (a) Nash, B. W.; Newberry, R. A.; Pickles, R.; Warburton, W.
K. J . Chem. Soc. C 1969, 2794. (b) F. Eloy, F.; Deryckere, A.; van
Overstraeten, A. Bull. Soc. Chim. Belg. 1969, 78, 47.
(23) Goncalves, H.; Mathis, F.; Foulcher, C. Bull. Soc. Chim. Fr.
1970, 2599.
(24) Perez, M. A.; Dorado, C. A.; Soto, J . L. Synthesis 1983, 483.
(25) Palazzo, G.; Strani, G. Gazz. Chim. Ital. 1961, 91, 216.
(26) Adembri, G.; Camparini, A.; Ponticelli, F. J . Chem. Soc., Perkin
Trans. 1 1981, 1703.
(27) Whitfield, L. L.; Papadopulos, E. P. J . Heterocycl. Chem. 1981,
18, 1197.

Photoinduced Molecular Rearrangements
J . Org. Chem., Vol. 61, No. 24, 1996 8401
1
1640 cm-1; H-NMR (DMSO-d6) δ 2.52 and 2.84 (2d, 3H, J )
radiation for 6 h gave starting material (0.2 g; 40%) and 19
(0.15 g; 28%).
4.5 Hz; 2s with D2O), 6.68-7.73 (m, 10H), 9.40-9.63 (m, 2H;
exchangeable with D2O); MS m/z 253 (M+), 222, 195, 180, 104,
93, 77. Anal. Calcd for C15H15N3O: C, 71.13; H, 5.97; N, 16.59.
Found: C, 71.30; H, 5.80; N,16.40. Lit.28 (Chem. Abstr.) does
not report mp, nor spectroscopic data. Careful hydrolysis of
26 in the presence of hydrochloric acid gave N-benzoyl-N′-
methylurea, mp 164-166 °C (from ethanol) (lit.29 mp 169-
170 °C). A sample of 26 has been obtained from ethyl
N-(methylaminocarbonyl)-N′-phenylbenzimidate, by adapting
the procedure reported.28
Similarly, irradiation of 13 (0.5 g) in the presence of
methanolic ammonia for 2 h and chromatography, together
with starting material (0.3 g; 60%) and traces of 24, gave 3,5-
d ip h en yl-1,2,4-tr ia zole (20) (0.05 g; 10%), mp 190 °C (from
aqueous ethanol) (lit.27 mp 191.5-192.5 °C).
Ir r a d ia tion of th e 3-(o-Am in op h en yl)-5-m eth yl-1,2,4-
oxa d ia zole (27). A sample of 27 (0.5 g) in methanol (100 mL)
was apportioned in eight Pyrex vessels and then irradiated
at λ ) 313 nm for 30 min, when the reaction was complete (by
TLC), and the photoproduct 35 partially separated. The
solvent was then reduced under vacuum, and the product was
filtered to give the 2-(a cetyla m in o)ben zim id a zole (35) (0.3
g), mp 315-320 °C (from ethanol) (lit.35 mp 312-315 °C).
Evaporation of the mother liquor and chromatography gave
the 3-(a cetyla m in o)in d a zole (32) (0.1 g; 20%) mp 200-204
°C (from water) (lit.12a mp 204 °C), and then additional 35 (0.05
g; total yield 70%). Analytical photochemistry [compound 27
(20 mg) in methanol (10 mL) was irradiated for 20 min, when
conversion of starting material was complete] gave 32 (25%)
and 35 (75%). Parallel irradiations (at λ ) 313 nm) in the
presence of piperylene or in the presence of methylamine, or
irradiations (at 360 nm) in the presence of benzophenone, did
not show any significative change.
Irradiation of 13 (0.5 g) in the presence of dimethylamine
for 6 h and chromatography returned starting material (0.08
g; 16%) and gave R-(N,N-d im eth ylh yd r a zon o)-N-ben zoyl-
ben zyla m in e (23) (0.3 g; 50%), mp 163 °C (from ethanol); IR
3300, 1670 cm-1 1H-NMR (DMSO-d6) δ 2.72 (s, 6H), 7.34-
;
Ir r a d ia t ion of 3-[o-(Met h yla m in o)p h en yl]-5-m et h yl-
1,2,4-oxa d ia zole (28). Irradiation (at λ ) 313 nm, 30 min)
of 28 (0.5 g) in methanol (100 mL) apportioned in eight pyrex
vessels and chromatography gave the 3-(a cetyla m in o)-1-
m eth ylin d a zole (33), (0.15 g; 30%), mp 142 °C (from water)
(lit.12a mp 142 °C), and then the 2-(a cetyla m in o)-1-m eth yl-
ben zim id a zole (36) (0.25 g; 50%), mp 182 °C (from methanol)
(lit.36 mp 182 °C). Analytical photochemistry as above gave
33 (30%) and 36 (70%).
8.09 (m, 10H), 10.13 (s, 1H); MS m/z 267 (M+). Anal. Calcd
for C16H17N3O: C, 71.89; H, 6.41; N, 15.72. Found: C, 71.80:
H, 6.30; N, 15.60. A sample of 23 has been prepared by
reacting the methyl N-benzoylbenzimidate24,30 with N,N-
dimethylhydrazine in methylene chloride.
Irradiation of 13 (0.5 g) in the presence of hydrazine for 6 h
and chromatography, besides minor components which were
discarded, returned starting material (0.15 g; 30%) and gave
1-a m in o-3,5-d ip h en yl-1,2,4-tr ia zole (21) (0.15 g; 28%), mp
192-195 °C (from ethanol) (lit.31 mp 195 °C).
Irradiation of 13 (0.5 g) in the presence of N,N-dimethyl-
hydrazine (3 mL) for 2 h and chromatography returned
starting material (0.3 g; 60%) and gave the N-benzoylbenza-
midine (0.05 g; 10%), mp 102-103 °C (from hexane) (lit.32 mp
98-100 °C). Irradiation for 6 h gave starting material (0.1 g;
20%), compound 24 (0.05 g; 10%), and N-benzoylbenzamidine
(0.2 g; 40%).
Ir r a d ia tion of th e Oxa d ia zole 14 in th e P r esen ce of
Meth yla m in e. Irradiation of 14 (0.5 g) for 2 h and chroma-
tography returned starting material (0.3 g; 60%) and gave the
2-m eth oxyqu in a zolin -4-on e (25) (0.02 g; 4%), mp 230-232
°C (lit.33 mp 230-232 °C) and then 3-m eth oxy-1-m eth yl-5-
p h en yl-1,2,4-tr ia zole (18) (0.1 g; 18%), mp 85-86 °C (from
light petroleum) (lit.34 mp 85-86 °C).
Ir r a d ia tion of th e Oxa d ia zole 15 in th e P r esen ce of
Meth yla m in e. Irradiation of 15 (0.5 g) for 2 h and chroma-
tography returned starting material (0.30 g; 60%) and gave
the 1,5-d im eth yl-3-p h en yl-1,2,4-tr ia zole (19) (0.1 g; 18%),
mp 115-116 °C (from hexane) (lit.24 mp 115-116 °C). Ir-
Ir r a d ia tion of 3-(o-Am in op h en yl)-5-p h en yl-1,2,4-oxa -
d ia zole (29). After irradiation (at λ ) 254 nm, 3 h) of
compound 29 (0.25 g) in methanol (100 mL) apportioned in
eight quartz vessels (when the conversion of starting material
was complete), the solvent was removed and the residue was
taken up with the minimum of ethanol and filtered to give
the 2-(ben zoyla m in o)ben zim id a zole (37), (0.2 g), mp 235-
237 °C (lit.37 mp 235-240 °C). Evaporation of the mother
liquor and chromatography gave additional 37 (0.05 g; total
yield 50%) and then the 3-(ben zoyla m in o)in d a zole (34) (0.2
g; 40%), mp 162-165 °C (from benzene) (lit.12b mp 161 °C).
Analytical irradiations gave 34 (45%) and 37 (55%). Analytical
irradiations of 29 at λ ) 313 nm in Pyrex vessels (4 h) gave
the following composition of the photolysate: starting material
29 (50%), 34 (15%), 37 (35%). Irradiations of 29 in the
presence of piperylene (at λ ) 254 nm) or benzophenone (at λ
) 360 nm) gave no changes.
Ack n ow led gm en t. Financial support by CNR (Ro-
ma) and MURST (Roma) is gratefully acknowledged. We
also thank C. Di Maio, S. Asta, and M. Cascino for
technical assistance.
(28) Etienne, A.; Lonchambon, G.; Roques, J .; Lemmens, B.; Pintard,
F. C. R. Hebd. Seances Acad. Sci., Ser. C 1978, 286, 91 (Chem. Abstr.
1978, 88, 136266r).
(29) Dobychina, N. S.; Antonova, T. V.; Murav'eva, Z. M. Izv. Tomsk.
Politekh. Inst. 1967, 148, 185 (Chem. Abstr. 1969, 71, 30190v).
(30) Bader, H. J . Org. Chem. 1965, 30, 707.
J O960765I
(31) Birkofer, L.; Ritter, A.; Richter, P. Chem. Ber. 1963, 96, 2750.
(32) Palazzo, G.; Strani, G.; Tavella, M. Gazz. Chim. Ital. 1961, 91,
1085.
(33) Tennant, G.; Vaughan, K. J . Chem. Soc. C 1966, 2287.
(34) Kubota, S.; Uda, M. Chem. Pharm. Bull. J pn 1973, 21, 1342.
(35) Lipnitskii, V. F.; Shvaika, O. P. Chem. Heterocycl. Compd.
(Engl. Transl.) 1985, 21, 954.
(36) Pozharskii, A. F.; Konstantinchenko, A. A.; Kashparov, I. S.
Chem. Heterocycl. Compd (Engl. Transl.) 1978, 14, 93.
(37) Biddle, P.; Lane, E. S.; Williams, J . L. J . Chem. Soc. 1960, 2369.