Photochemistry of fluorinated heterocyclic compounds. An expedient route for the synthesis of fluorinated 1,3,4-oxadiazoles and 1,2,4-triazoles

Article abstract of DOI:10.1021/jo049814e

The photochemistry of some 3-N-alkylamino-5-perfluoroalkyl-1,2,4-oxadiazoles in the presence of nitrogen nucleophiles such as ammonia and primary and secondary aliphatic amines has been investigated. The primary photolytic intermediate from the cleavage o

Full text of DOI:10.1021/jo049814e

P h otoch em istr y of F lu or in a ted Heter ocyclic Com p ou n d s.
An Exp ed ien t Rou te for th e Syn th esis of F lu or in a ted
1,3,4-Oxa d ia zoles a n d 1,2,4-Tr ia zoles
Andrea Pace, Ivana Pibiri, Silvestre Buscemi, and Nicolo` Vivona*
Dipartimento di Chimica Organica “E. Paterno`”, Universita` degli Studi di Palermo,
Viale delle Scienze-Parco d’Orleans II, I-90128 Palermo, Italy
Luciana Malpezzi
Dipartimento di Chimica, Materiali e Ingegneria Chimica, Politecnico di Milano, Via Mancinelli 7,
I-20131 Milano, Italy
nvivona@unipa.it
Received February 2, 2004
The photochemistry of some 3-N-alkylamino-5-perfluoroalkyl-1,2,4-oxadiazoles in the presence of
nitrogen nucleophiles such as ammonia and primary and secondary aliphatic amines has been
investigated. The primary photolytic intermediate from the cleavage of the ring O-N bond follows
two distinct and competing pathways leading to (i) 5-perfluoroalkyl-1,3,4-oxadiazoles, through the
ring contraction-ring expansion photoisomerization route favored by the presence of the base or
(ii) 5-perfluoroalkyl-1,2,4-triazoles, through the intervention, as an internal nucleophile, of the
exocyclic N-alkylamino moiety of the oxadiazole followed by the attack of the external nitrogen
nucleophile and subsequent heterocyclization. Some comments on the photoreactivity of fluorinated
oxadiazoles and on the applications of these photoprocesses in the synthesis of target fluorinated
structures are emphasized. In this context, irradiations of 3-perfluoroalkanoylamino-4-phenylfurazan
in the presence of primary aliphatic amines are reconsidered as feasible one-pot synthetic
methodologies toward fluorinated heterocycles. X-ray analysis of two representative products
1-methyl-3-methylamino-5-perfluoroheptyl-1,2,4-triazole and 2-methylamino-5-trifluoromethyl-1,3,4-
oxadiazole confirmed the proposed structures and furnished interesting information on the crystal
packing of these fluorinated five-membered heterocycles.
In tr od u ction
sors.2 Within the building-block strategy, an expedient
route can be recognized in the ring-rearrangement reac-
tions, which can be thermally or photochemically pro-
moted.3-5 This means that a readily available fluorinated
Fluorinated heterocycles represent an interesting class
of fluorinated compounds that have found their wide
application as agrochemicals, pharmaceuticals, and in the
field of new materials science.1 For this reason, an
intriguing research area is looking at the development
of new methodologies for the synthesis of these target
structures.2 Besides the direct fluorination or perfluoro-
alkylation reactions, a general and more convenient
approach to fluorinated heterocyclic compounds considers
the building-block strategy, which is the construction of
the fluorinated heterocyclic structure by conventional
heterocyclization reactions of acyclic fluorinated precur-
(2) (a) Chambers, R. D.; Sargent, C. R. Adv. Heterocycl. Chem. 1981,
28, 1-71. (b) Differding, E.; Frick, W.; Lang, R. W.; Martin, P.; Schmit,
C.; Veenstra, S.; Greuter, H. Bull. Soc. Chim. Belg. 1990, 99, 647-
671 (c) Silvester, M. J . Adv. Heterocycl. Chem. 1994, 59, 1-38. (c)
Burger, K.; Wucherpfennig, U.; Brunner, E. Adv. Heterocycl. Chem.
1994, 60, 1-64. (d) Furin, G. G. Targets in Heterocyclic Systems;
Attanasi, O. A., Spinelli, D., Eds.; Societa Chimica Italiana: Roma,
1998; Vol. 2, pp 355-441. (e) Zhu, S. Z.; Wang, Y. L.; Peng, W. M.;
Song, L. P.; J in, G. F. Curr. Org. Chem. 2002, 6, 1057-1096.
(3) For heterocyclic rearrangements, see: (a) Van der Plas, H. C.
Ring Transformations of Heterocycles; Academic: New York, 1973;
Vols. 1 and 2. (b) Boulton, A. J .; Katritzky, A. R.; Hamid, A. M. J .
Chem. Soc. C 1967, 2005-2007. (c) Afridi, A. S.; Katritzky, A. R.;
Ramsden, C. A. J . Chem. Soc., Perkin Trans. 1 1976, 315-320. (d)
Ruccia, M.; Vivona, N.; Spinelli, D. Adv. Heterocycl. Chem. 1981, 29,
141-169. (e) L’abbe´, G. J . Heterocycl. Chem. 1984. 21, 627-638. (f)
Vivona, N.; Buscemi, S.; Frenna, V., Cusmano, G. Adv. Heterocycl.
Chem. 1993, 56, 49-154.
(4) Van der Plas, H. C. Adv. Heterocycl. Chem. 1999, 74, 1-253.
(5) For photoinduced rearrangements of five-membered heterocycles,
see: (a) Padwa, A. In Rearrangements in Ground and Excited States;
de Mayo, P., Ed.; Academic Press: New York, 1980; Vol. III, pp 501-
547. (b) D’Auria, M. Heterocycles 1999, 50, 1115-1135. (c) D’Auria,
M. In Targets in Heterocyclic Systems; Attanasi, O. A., Spinelli, D.,
Eds.; Societa` Chimica Italiana: Roma, 1999; Vol. 2, pp 233-279. (d)
D’Auria, M. Adv. Heterocycl. Chem. 2001, 79, 41-88.
(1) See, among others: (a) Hudlicky, M. Chemistry of Organic
Fluorine Compounds, 2nd ed.; Ellis Horwood: Chichester, 1976. (b)
Filler, R.; Organofluorine Chemicals and Their Industrial Applications;
Banks, R. E., Ed.; Ellis Horwood: Chichester, 1979. (c) Filler, R.;
Kobayashi, Y. Biomedical Aspects of Fluorine Chemistry; Kodansha &
Elsevier Biomedical: Tokyo, 1982. (d) Welch, J . T. Tetrahedron 1987,
43, 3123-3197. (e) Reynolds, D. W.; Cassidy, P. E.; J ohnson, C. G.;
Cameron, M. L. J . Org. Chem. 1990, 55, 4448-4454. (f) Filler, R.;
Kobayashi, Y.; Yagupolskii, L, M. Organofluorine Compounds in
Medicinal Chemistry and Biomedical Applications; Elsevier: Amster-
dam, 1993. (g) Chemistry of Organic Fluorine Compounds II. A Critical
Review; Hudlicky, M., Pavlath, A. E., Eds.; ACS Monograph 187;
American Chemical Society: Washington, DC, 1995.
10.1021/jo049814e CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/08/2004
4108
J . Org. Chem. 2004, 69, 4108-4115

Photochemistry of Fluorinated Heterocyclic Compounds
SCHEME 1
C(3) of the ring and favored by the presence of a base in
the irradiation medium.15,16 Tautomeric or acid-base
equilibria in the starting oxadiazole or in the key
intermediates have been claimed to occur during the
transformation framed in the ring contraction-ring
expansion pattern.15 Moreover, depending on the nature
of the substituent at C(5) of the oxadiazole ring, the
occurrence of a competing photorearrangement through
an internal cyclization-isomerization pathway5 leading
to the ring-degenerate isomers has been pointed out.16
Irradiations performed on the fluorinated analogues
opened the way toward a more complete understanding
of the general behavior of this quite interesting hetero-
cycle. During our study on the photoreactivity of 3-amino-
5-perfluoroalkyl-1,2,4-oxadiazoles 6, we have recently
reported17 that these compounds show a marked photo-
reactivity that can be ascribed to a synergic effect of the
amino group at C(3) and the perfluoroalkyl moiety at C(5)
of the oxadiazole ring. In this context, we have observed
that (i) irradiation of 6 (at λ ) 313 nm) in methanol easily
gave the solvolysis product 4 as a major component (by
a reaction of the nucleophilic solvent with the electro-
philic nitrogen of the photolytic species) and 5 (from an
addition of the solvent to a nitrilimine species arising
from an endocyclic diazirine intermediate (see after)) and
(ii) similarly to what was observed for nonfluorinated
analogues, irradiation of 6 (at λ ) 313 nm) in methanol
and in the presence of TEA gave competing phototrans-
position pathways leading to the ring-isomers 1,3,4-
oxadiazoles 8 (through a ring contraction-ring expansion
route) and the ring-degenerate oxadiazoles 7 (through an
internal cyclization-isomerization route) (Scheme 2).17
Interestingly, the formation of the solvolytic compound
4 disclosed the electrophilic behavior of the nitrogen
originally bound to the oxygen and opened the possibility
to realize synthetic methodologies for different perfluo-
roalkyl-heterocycles or their open-chain precursors by
irradiations of fluorinated 1,2,4-oxadiazoles in the pres-
ence of different nucleophiles. Actually, this approach has
been utilized in the photochemistry of some nonfluori-
nated 1,2,4-oxadiazoles in the presence of nitrogen- or
sulfur-containing nucleophiles.13a,b In this paper we
report investigations on the photochemical behavior of
the 3-N-alkylamino-1,2,4-oxadiazoles 9a ,b and 24 irradi-
ated in the presence of nitrogen nucleophiles. Moreover,
irradiations of the 3-perfluoroalkanoylamino-4-phenyl-
furazan 1a ,b and 28 in the presence of primary aliphatic
amines will be reconsidered as feasible one-pot proce-
dures for the synthesis of fluorinated 1,3,4-oxadiazoles
and 1,2,4-triazoles.
heterocycle could be used as a precursor to be rearranged
into a new fluorinated structure that could be otherwise
constructed with difficulty or by means of tedious pro-
cedures.
Examples of this approach come from our laborato-
ries.6-9 They regard photoinduced rearrangements of
O-N bond-containing azoles,6,7 as well as ANRORC-like
rearrangements4 of 5-perfluoroalkyl-1,2,4-oxadiazoles.9,10
As an example of the photochemical approach, photolysis
of 3-perfluoroalkanoylamino-furazans 1 in methanol and
in the presence of ammonia or primary aliphatic amines
allowed the synthesis of 3-amino- or 3-N-alkylamino-5-
perfluoroalkyl-1,2,4-oxadiazoles 2 (Scheme 1).6 This pho-
toreaction follows the photofragmentation pattern5a,11 of
the furazan ring into benzonitrile and an acylamino-
nitriloxide species that the nitrogen nucleophile will
capture to give the N-acylamino-amidoxime intermediate
3 as a precursor of final oxadiazoles 2. Yields of isolated
oxadiazoles 2 were not excellent, and this is due to the
photoreactivity of these compounds (unlike nonfluori-
nated analogues12) under the irradiation conditions.
Besides the possibility of performing synthetic method-
ologies, these photochemical studies raised the issue of
the photoreactivity of fluorinated heterocycles.
As far as 1,2,4-oxadiazoles are concerned, this hetero-
cycle presents photoreactivities that are strongly depend-
ent on several factors such as the nature and position of
the substituents or the presence of nucleophiles or bases
in the photoreaction media.11a,13-16 A particular case of
photoreactivity is represented by the ring-photoisomer-
ization into 1,3,4-oxadiazoles, which was found to be
restricted to 1,2,4-oxadiazoles bearing an XH group at
(6) Buscemi, S.; Pace, A.; Vivona, N. Tetrahedron Lett. 2000, 41,
7977-7981.
(7) Buscemi, S.; Pace, A.; Calabrese, R.; Vivona, N.; Metrangolo, P.
Tetrahedron 2001, 57, 5865-5871.
(13) For photoinduced rearrangements involving the 1,2,4-oxadiazole
heterocycle, see also: (a) Buscemi. S.; Vivona, N.; Caronna, T. J . Org.
Chem. 1996, 61, 8397-8401. (b) Vivona, N.; Buscemi, S.; Asta, S.;
Caronna, T. Tetrahedron 1997, 53, 12629-12636. (c) Buscemi, S.; Pace,
A.; Vivona, N.; Caronna, T.; Galia, A. J . Org. Chem. 1999, 64, 7028-
7033.
(14) (a) Newman, H. Tetrahedron Lett. 1968, 2417-2420 (b) New-
man, H. Tetrahedron Lett. 1968, 2421-2424.
(15) (a) Buscemi. S.; Cicero, M. G.; Vivona, N.; Caronna, T. J . Chem.
Soc., Perkin Trans. 1 1988, 1313-1315. (b) Buscemi. S.; Cicero, M.
G.; Vivona, N.; Caronna, T. J . Heterocycl. Chem. 1988, 25, 931-935.
(c) Buscemi, S.; Pace, A.; Vivona, N.; Caronna, T. J . Heterocycl. Chem.
2001, 38, 777-780.
(8) Buscemi, S.; Pace, A.; Pibiri, I.; Vivona, N. Heterocycles 2002,
57, 1891-1896.
(9) (a) Buscemi, S.; Pace, A.; Pibiri, I.; Vivona, N.; Spinelli, D. J .
Org. Chem. 2003, 68, 605-608. (b) Buscemi, S.; Pace, A.; Pibiri, I.;
Vivona, N.; Zaira Lanza, C.; Spinelli, D. Eur. J . Org. Chem. 2004, 0000.
(10) These ANRORC-like rearrangements appear determined by the
presence of the perfluoroalkyl group at C-5 of the oxadiazole.9 The
Addition of the Nucleophile on the C-5 is followed by Ring Opening
and then Ring Closure by attack of the â nucleophilic center of the
bidentate reagent (hydrazine or hydroxylamine) at the C-3 of the initial
oxadiazole ring, a molecule of hydroxylamine being displaced in the
final step.
(11) (a) Vivona, N.; Buscemi, S. Heterocycles 1995, 41, 2095-2116
and references therein. (b) Buscemi, S.; Vivona, N.; Caronna, T. J . Org.
Chem. 1995, 60, 4095-4101.
(16) Buscemi, S.; Pace, A.; Pibiri, I.; Vivona, N. J . Org. Chem. 2002,
67, 6253-6255.
(17) Buscemi, S.; Pace, A.; Pibiri, I.; Vivona, N.; Caronna, T. J .
Fluorine Chem. 2004, 125, 165-173.
(12) Buscemi, S.; Vivona, N.; Caronna, T. Synthesis 1995, 917-919.
J . Org. Chem, Vol. 69, No. 12, 2004 4109

Pace et al.
SCHEME 2
SCHEME 4
was detected. Oxadiazoles 10a ,b on one hand and tria-
zoles 11 or 12 on the other must be considered primary
photoproducts, as they do not interconvert each other
under the used photoreaction conditions and their forma-
tion takes place even at low conversion of the starting
substrate.
SCHEME 3
As previously documented17 for 3-amino-5-perfluoro-
alkyl-1,2,4-oxadiazoles irradiated in the presence of TEA,
the formation of the 1,3,4-oxadiazoles 10 clearly arises
from the ring contraction-ring expansion photoisomer-
ization route through the diazirine 18, whose ring expan-
sion into 10 could be favored by the presence of the base
methylamine (Scheme 4).18 On the other hand, the
concomitant formation of the 1-methyl-1,2,4-triazoles 11
and 12 (structure of representative compound 11 was
confirmed by X-ray analysis), as well as their analogues
13-15 (see after), is a surprising result. In fact, on the
basis of the previously reported reactivity of 1,2,4-
oxadiazoles,13a one could have explained the formation
of 1-methyl-3-N-methylamino-triazole 11 during the
reaction of 9a with methylamine by assuming a direct
reaction between the photolytic species 17 and methyl-
amine in a N-N bond formation pattern, followed by
cyclodehydration of the resulting intermediate 21 (Z )
NHMe). However, this reaction pattern must be excluded
because during the irradiations in the presence of nitro-
gen nucleophiles different than methylamine there is no
evidence of such attack: irradiation of the representative
oxadiazole 9a in the presence of ammonia, propylamine,
or pyrrolidine, besides the photoisomer 1,3,4-oxadiazole
10a (as major component), produced the 3-amino- (or 3-N-
alkyl-amino)-1-methyl-1,2,4-triazoles 13, 14, and 15,
respectively.
Resu lts a n d Discu ssion
We initially observed that during the irradiation of
3-amino compound 6a in the presence of an excess of
methylamine, the amine was not incorporated in the final
products; the exclusive formation of 8a and 7a indicated
that the methylamine acted as a base (similarly to what
was observed17 in the TEA-assisted photoreactions) rather
than as a nucleophile involved in the reaction. Quite
different results were found in the case of 3-N-methyl-
amino-oxadiazoles 9. In fact, irradiation of oxadiazoles
9a ,b in the presence of an excess of methylamine es-
sentially gave a mixture of the ring photoisomer 1,3,4-
oxadiazoles 10a ,b and 1,2,4-triazoles 11 and 12, respec-
tively (Scheme 3). In a typical experiment, irradiation of
9a gave 10a and 11 in 27% and 25% yields, respectively.
Unexpectedly, no ring-degenerate rearrangement to 5-N-
methylamino-1,2,4-oxadiazole 16 (whose formation should
have implied an internal cyclization-isomerization route)
(18) As previously observed,15c,16,17 the presence of an XH moiety at
C-3 of the 1,2,4-oxadiazole heterocycle is needed for the ring photo-
isomerization to occurr, and this is valid for both fluorinated and
nonfluorinated substrates. Therefore, in the presence of a base, the
involvement of deprotonated species from 3-N-methylaminooxadiazoles
9 in the reaction pathway cannot be excluded. In this context, it is
worthy to note that the NH moiety of the starting oxadiazole is
expected to show a significant acidity in the excited state and could
be efficiently deprotonated.
4110 J . Org. Chem., Vol. 69, No. 12, 2004

Photochemistry of Fluorinated Heterocyclic Compounds
SCHEME 5
SCHEME 6
In these products, the nitrogen nucleophile is found
attached at C(3) and the presence of the methyl moiety
at N(1) suggests that the exocyclic nitrogen of the
methylamino group in the original 1,2,4-oxadiazole has
a primary role in the reaction pattern (Scheme 5). From
the common photolytic intermediate 17, the methylamino
group can either form a diazirine 19 or directly transpose
to the carbodiimide 20. The nucleophilic attack of the
external reagent at C(3) of the diazirine 19 or at the
carbodiimidic species 20 and the subsequent heterocy-
clization of the resulting acylaminoamhydrazones 21 will
lead to the final 1-methyl-1,2,4-triazoles 11-15 (Scheme
5). These findings constitute a peculiar photoreactivity
of the 3-N-methylamino-substituted 1,2,4-oxadiazole sys-
tem, not observed in the case of 3-amino-5-perfluoroalkyl-
oxadiazoles nor in the case of nonfluorinated 3-amino-
oxadiazoles. Examples proceeding through a carbodiimidic
intermediate arising from migration of the C(3) group to
the electrophilic N(2) of the photolytic species in the pho-
tochemistry of 1,2,4-oxadiazoles have been reported.13a,15b
Moreover, a 1,2,4-oxadiazole ring-opening reaction in-
volving diazirines formed bethween exocyclic nitrogen at
C(3) and N(2) of the oxadiazole ring has been suggested
in the base-induced rearrangement of some 3-N-aryl-
amino-5-methoxy-1,2,4-oxadiazoles19 and of some N-(1,2,4-
oxadiazol-3-yl)-â-enamino ketones.20 In our case, the
diazirine 19 formed with the exocyclic nitrogen must
arise from a photochemical reaction, that is, through a
preliminary formation of the photolytic species 17; this
is confimed by a separate experiment carried out in the
dark on compound 9a from which no base-induced
thermal process was observed.
of compounds 9a ,b in methanol and in the presence of
TEA. In this case, besides the expected ring-photoisomer
1,3,4-oxadiazoles 10a ,b (major component), the 3-meth-
oxy-1,2,4-triazoles 22 were isolated21 (Scheme 6), while
the ring-degenerate 5-N-methylamino-1,2,4-oxadiazoles
such as 16 were not detected. Obviously, formation of
3-methoxy-triazoles 22 agrees with our hypothesis of an
involvement of the exocyclic diazirine 19 (or the open-
chain carbodiimide 20) subsequently attacked by the
nucleophilic solvent.
Overall, the experimental results show that both 3-N-
methylamino-1,2,4-oxadiazoles 9 and 3-amino analogues
6 photorearrange into the corresponding 1,3,4-oxadia-
zoles through the ring contraction-ring expansion route
involving an exocyclic diazirine intermediate. As pointed
out in the Introduction, besides this common route, the
3-amino compounds presented an additional reaction
involving an internal cyclization-isomerization route.
However, in the case of our 3-N-methylamino derivatives,
a different competing reaction is observed, involving the
exocyclic diazirine (or carbodiimide) route leading to
1,2,4-triazoles. A speculative hypothesis to explain this
different behavior considers that the methylamino group
could play a significant role both in stabilizing the
photolytic intermediate and in assisting either the exo-
cyclic diazirine formation or its transposition to the
electrophilic N-2, thus favoring photoreactions involving
these species.
The peculiar photoreactivity of 3-N-methylamino oxa-
diazoles is also observed when photolysis was carried out
in methanol only; irradiation of representative 9a gave
Interestingly, the above concomitant pathways involv-
ing both endo- and exocyclic nitrogen in the formation of
the intermediates take also place during the irradiation
(21) In an independent experiment, aminolysis on representative
3-methoxy-triazole 22a in the presence of methylamine left the starting
material unchanged, thus excluding that compounds 11-15 could be
formed by an aminolysis reaction of the first formed compounds 22
with the employed amines.
(19) J ones, S. S.; Staiger, D: B.; Chodosh, D. F. J . Org. Chem. 1982,
47, 1969-1971.
(20) Braun, M.; Buchi, G.; Bushey, D. F. J . Am. Chem. Soc. 1978,
100, 4209-4213.
J . Org. Chem, Vol. 69, No. 12, 2004 4111

Pace et al.
SCHEME 7
SCHEME 8
the open-chain product 23 on one hand (as a result of
solvolysis of the endo diazirine 18) and 3-methoxy-
triazole 22a on the other (Scheme 6). Treatment of 23
with hydrochloric acid in methanol gave the ring-pho-
toisomer 10a , confirming the assigned structure.22 In
contrast with what observed in the case of 3-amino
compounds 6 (Scheme 2; formation of open-chain prod-
ucts 4), insertion of methanol into the electrophilic
nitrene-like nitrogen of the photolytic species 17 in a
O-N bond formation pattern has not been observed. In
this case, besides the lower electrophilic character of the
N-2 site due to the N-methylamino group, one can simply
consider that the pathways that allow the species 17 to
develop into 18 and 23 on one hand and into triazole 22
on the other are kinetically more favored than the
bimolecular nucleophilic attack at N-2 by the nucleophilic
solvent.
Besides the quite interesting insight that these pho-
toreactions gave on the reactivity of the 1,2,4-oxadiazole
ring, we also wanted to evaluate the applications of this
photochemical approach in synthesis. In view of this, we
at first considered extension of the above reactivity to
the 3-N-propylamino-oxadiazole 24 (Scheme 7). As ex-
pected, irradiation of 24 in the presence of methylamine
allowed us to obtain the 1,3,4-oxadiazole 26 on one hand
and the 1,2,4-triazole 25 on the other. Moreover, irradia-
tion of 24 in methanol and TEA produced 26 and 27.
Furthermore, taking into account the synthetic procedure
leading to 3-N-alkylamino-5-perfluoroalkyl-1,2,4-oxadia-
zoles (that is, irradiation of 3-perfluoroalkanoylamino-
furazans in the presence of primary aliphatic amines; see
Scheme 1),6 we reconsidered irradiation of perfluoroal-
kanoylamino-furazans 1a ,b in the presence of an excess
of methylamine, aiming to realize one-pot phototrans-
formations. In a typical experiment, irradiation of com-
pound 1a in the presence of an excess of methylamine,
besides the 3-N-methylamino oxadiazole 9a (42%), al-
lowed us to obtain the 2-N-methylamino-1,3,4-oxadiazole
10a (25%) and the 3-N-methylamino-1,2,4-triazole 11
(17%). Similarly, prolonged irradiation of 1b in the
presence of an excess of methylamine gave compounds
9b (9%), 10b (49%), and 12 (10%).23
This one-pot methodology appears of some interest,
particularly when 1,2,4-oxadiazole intermediates, such
as trifluoromethylated compounds 29, are difficult to be
isolated. As expected, one-pot irradiation of compound
28 in the presence of an excess of methylamine or
propylamine allowed us to isolate the 2-N-alkylamino-
5-trifluoromethyl-1,3,4-oxadiazoles 30a (32%) (structure
confirmed by X-ray analysis) or 30b (32%) and 1-alkyl-
3-N-alkylamino-1,2,4-triazoles 31a (15%) or 31b (27%)
(Scheme 8). The involvement of the 1,2,4-oxadiazoles 29
as intermediates has been proved by isolating compound
29a (in low yields, indeed) that irradiated in the same
conditions gave 30a and 31a .
X-r a y Cr ysta llogr a p h ic An a lysis. The X-ray diffrac-
tion analysis of the two representative products 1-methyl-
3-N-methylamino-5-perfluoroheptyl-1,2,4-triazole (11) and
2-N-methylamino-5-trifluoromethyl-1,3,4-oxadiazole (30a)
was carried out to assess the conformation of the two
compounds and to have information on the crystal
packing of these target fluorinated five-membered het-
erocycles.
Compound 11 may be regarded as consisting of two
moieties: the 1-methyl-3-N-methylamino-1,2,4-triazole
and the perfluoroalkyl chain. The perfluorinated chain
displays a “pony-tail” behavior, exhibiting thermal motion
or disorder that increases toward the tail end. This
disorder is typically found in crystal structures having a
perfluoroalkyl chain;24 however, it is unambiguously
found that the alkyl chain adopts a nearly fully extended
conformation, with the chain C-C-C-C torsion angles
ranging between 163° and 175°.
(23) This observation explains low yields of 3-amino- (or 3-N-
alkylamino-)1,2,4-oxadiazoles obtained in the irradiation of 3-perfluo-
roalkanoylamino furazans in the presence of ammonia or aliphatic
primary amines (see Scheme 1).6
(24) (a) Kromm, P.; Bideau, J . P.; Cotrait, M.; Destrade, C.; Nguyen,
H. Acta Crystallogr. 1994, C50, 112-115. (b) J essop, P. G.; Olmstead,
M. M.; Ablan, C. D.; Grabenauer, D. S.; Eckert, C. A.; Liotta, C. L.
Inorg. Chem. 2002, 41, 3463-3468. (c) Croxtall, B.; Fawcett, J .; Hope,
E. G.; Stuart, A. M. J . Fluorine Chem. 2003, 119, 65-73.
(22) For the open-chain compound 23, one could anticipate different
tautomeric hydrogen-bonded structure or ring-chain equilibria. How-
ever, this structural aspect has not been developed in this study.
4112 J . Org. Chem., Vol. 69, No. 12, 2004

Photochemistry of Fluorinated Heterocyclic Compounds
A systematic search on the crystallographic Cambridge
Structural Database (CSD)25 revealed only two entries
with the same moiety [refcodes FECQAF26a and LER-
KEY26b]. The hetero-substituted rings of compound 11
and of compound LERKEY are fully planar, whereas the
structure FECQAF shows an angle of ca. 24° between
the ring plane and the plane defined by the methylamino
group. In all the three molecules the N(2) of the triazol
ring and the methyl of the methylamino moiety are syn
with respect to the C(3)-NHMe exocyclic bond. In 11 the
plane defined by the nearly all-anti alkyl chain is rotated
ca. 90° out of the triazole plane. In the crystal, the
perfluoroalkyl chains are aligned in a distinct fluorous
domain in a packing arrangement observed also for the
other fluorinated structures above cited.24
way to obtain the above fluorinated compounds when
nonphotochemical methodologies present some difficul-
ties.
This study has also a significant mechanistic impor-
tance as the information gained in this work allows more
insight in the photoreactivity of the 1,2,4-oxadiazole
heterocycle. We have already described previous reac-
tions as strongly dependent on substituents and experi-
mental conditions; under the light of these new results
we can indicate that a 5-perfluoroalkyl group, as well as
a 3-amino on one hand and a 3-N-alkylamino group on
the other, play a decisive role in the different primary
photochemical pattern that will subsequently develop, by
means of intra- or intermolecular processes, into the final
products.
The crystal structure of compound 30a contains two
independent molecules in the unit cell. An inspection on
the CSD with respect to the molecular moiety of 30a
revealed 3 entries [refcodes QACLAH,27a XIHSEM,27b and
ZAMKUT27c]. Molecules of compounds 30a and XIHSEM
are completely planar, with a syn conformation of the
N(3) of the oxadiazole ring and the methyl of the
methylamino moiety with respect to the C(2)-NHMe
exocyclic bond. In compound QACLAH, the methylamino
plane is rotated of ca. 30° out of the oxadiazole plane.
Structure ZAMKUT is nearly planar. The crystal packing
of 30a is characterized by infinite and parallel ribbons
of hydrogen-bonded molecules.
Exp er im en ta l Section
Gen er a l Meth od s a n d Ma ter ia ls. Melting points were
determined with a hot-stage apparatus and are uncorrected.
IR spectra were recorded from Nujol mulls or in CHCl3, when
1
indicated. H NMR spectra (250 MHz) were taken with TMS
as internal standard. Flash chromatography was performed
by using mixtures of ethyl acetate and light petroleum (fraction
boiling in the range of 40-60 °C) in varying ratios. Freshly
prepared saturated methanolic ammonia, ethanolic (33%)
methylamine, propylamine, freshly distilled pyrrolidine, and
triethylamine (TEA) (99.9%) were used as reagents. Photo-
chemical reactions were carried out in anhydrous methanol
in Pyrex vessels, by using a photoreactor, equipped with 16
Hg lamps irradiating at 313 nm (RPR-3000 Å) and a merry-
go-round apparatus set up for nine tubes. Pyrex tubes either
of 20 or 50 mL capacity were employed. X-ray data were
collected on an automatic diffractometer.
Con clu sion s
As a result of to their peculiar properties, fluorinated
1,3,4-oxadiazoles have recently found their application
in several fields.28 Taking into account our previous
work17 and present results, our photochemical approach
offers a way to synthesize 1,3,4-oxadiazoles where the
fluorinated group at C(5) can be varied to tune the
physicochemical properties of the compound, and the
amino group at C(2) can represent an ideal linking group
for the functionalization of different structures. The same
considerations can be made for fluorinated 1,2,4-triazoles,
for which some applications as ionic liquids are recently
reported.29 Interestingly, our representative compound
11 showed in its crystal packing the formation of an
oriented fluorous domain whose dimension could poten-
tially be varied by changing the length of the perfluoro-
alkyl chain. Over all, from a synthetic point of view, this
photochemical approach could represent an alterative
Compounds 1a ,b,6,12 6a ,6 9a ,b,6 and 246 were obtained as
reported. Compound 28 was prepared by a similar procedure,
as reported below.
3-Tr iflu or oa ceth yla m in o-4-p h en ylfu r a za n (28). To a
solution of 3-amino-4-phenylfurazan (2.3 g; 0.014 mol) in
anhydrous benzene (400 mL) was added trifluoroacetic anhy-
dride (8 mL; 0.056 mol) diluted in anhydrous benzene (100
mL) dropwise, and then the reaction mixture was stirred at
room temperature for 3 h. After removal of the solvent, workup
with water and filtration gave 3-trifluoroacetylamino-4-phen-
ylfurazan (28) (3.2 g; 93%) mp 80-81 °C (from benzene/light
petroleum). IR: 3258, 1726 cm-1 1H NMR (CDCl3): δ 7.58
.
(m, 5H), 8.46 (br s, 1H). MS: m/z 257 (28) (M+), 188 (10), 161
(100), 104 (70), 69 (50). Anal. Calcd for C10H6F3N3O2: C, 46.70;
H, 2.35; N, 16.34. Found: C, 46.80; H, 2.40; N, 16.40.
Ir r a d ia tion of Oxa d ia zole 6a in th e P r esen ce of Meth -
yla m in e. To a solution of compound 6a (10 mg) in methanol
(10 mL) purged by nitrogen bubbling was added a 10-fold
excess of methylamine, and the mixture was irradiated for 1
h. GC/MS analysis of photolyzate gave starting material and
compounds 7a and 8a .17 No evidence indicating incorporation
of the methylamine was detected.
(25) Allen, F. H. Acta Crystallogr. 2002, B58, 380-388.
(26) (a) Gyorgydeak, Z.; Holzer, W.; Kunz, R. W.; Linden, A.
Monatsh. Chem. 1995, 126, 733-746. (b) Pohl, M.; Bechstein, U.;
Paetzel, M.; Liebscher, J .; J ones, P. G. J . Prakt. Chem.-Chem.-Zeitung
1992, 334, 630-636.
Gen er a l P r oced u r e for P h otoch em ica l Rea ction s. A
solution of the 3-alkylamino-5-perfluoroalkyl-1,2,4-oxadiazoles
9a ,b or 24 or the 3-perfluoroalkanoylamino-4-phenyl-furazans
1a ,b or 28 in anhydrous methanol was apportioned into a
series of Pyrex tubes and then purged by nitrogen bubbling.
Then, a 10-fold excess (unless otherwise indicated) of ethanolic
methylamine, methanolic ammonia, pyrrolidine, propylamine,
or TEA was added to each tube, and all tubes were irradiated
for the time indicated. Concentrations of the substrate and
irradiation times were chosen in order to minimize the
formation of secondary photoproducts (monitoring the reaction
by TLC and GC/MS). After removal of the solvent under
reduced pressure, the residue was chromatographed. As neces-
(27) (a) Zhong, L.; Zhixiang, Z.; Gonghua, S.; Xuhong, Q.; J ie, S. J .
Chem Res. 1999, 66. (b) Gomez-Saiz, P.; Garcia-Tojal, J .; Maestro, M.
A.; Arnaiz, F. J .; Rojo, T. Inorg. Chem. 2002, 41, 1345-1347. (c) Wang,
X.; Wang, W.; Liu, H. Acta Crystallogr. 1995, C51, 1585-1587.
(28) See, for example: (a) Lavrenko, P.; Okatova, O.; Strelina, I.;
Bruma, M.; Schulz, B. Polymer 2003, 44, 2919-2925. (b) Hamciuc, E.;
Hamciuc, C.; Sava, I.; Bruma, M. Eur. Polym. J . 2001, 37, 287-293.
(c) Sitzmann, M. E. J . Fluorine Chem. 1995, 70, 31-38. (d) Cao, S.;
Qian, X.; Song, G.; Huang, Q. J . Fluorine Chem. 2002, 117, 63-66. (e)
Zheng, X.; Li, Z.; Wang, Y.; Chen, W.; Huang, Q.; Liu, C.; Song, G. J .
Fluorine Chem. 2003, 123, 163-169.
(29) (a) Mirzaei, Y. R.; Twamley, B.; Shreeve, J . M. J . Org. Chem.
2002, 67, 9340-9345. (b) Mirzaei, Y. R.; Shreeve, J . M. Synthesis 2003,
24-26. (c) Xue, H.; Twamley, B.; Shreeve, J . M. J . Org. Chem. 2004,
69, 1397-1400.
J . Org. Chem, Vol. 69, No. 12, 2004 4113

Pace et al.
sary, elution was carefully monitored by GC/MS. When
otherwise not specified, yields reported refer to the isolated
products.
g; 53%). Compound 15 had mp 62-65 °C (from light petro-
leum). 1H NMR (CDCl3): δ 1.96 (m, 4H), 3.43 (m, 4H), 3.88 (t,
3H; J H-F ) 1.5 Hz). MS: m/z 520 (100) (M+), 491 (4), 70 (5),
42 (3). Anal. Calcd for C14H11F15N4: C, 32.32; H, 2.13; N, 10.77.
Found: C, 32.40; H, 2.20; N, 10.90.
Ir r a d ia tion of Oxa d ia zole 9a in th e P r esen ce of Meth -
yla m in e. A sample of compound 9a (0.15 g; 0.3 mmol) in
methanol (150 mL) was apportioned into nine Pyrex tubes.
An excess of methylamine was added, and the solution was
irradiated for 30 min. Chromatography of the residue returned
starting material (0.027 g; 20%) and gave 1-methyl-3-N-
methylamino-5-pentadecafluoroheptyl-1,2,4-triazole (11) (0.037
g; 25%) and 2-N-methylamino-5-pentadecafluoroheptyl-1,3,4-
oxadiazole (10a ) (0.04 g; 27%). Compound 11 had mp 115-
Ir r a d ia tion of Oxa d ia zole 9a in th e P r esen ce of Tr i-
eth yla m in e (TEA). A sample of compound 9a (0.5 g; 1.0
mmol) in methanol (500 mL) was apportioned into three series
of nine Pyrex tubes. An excess of TEA was added, and all of
the samples were irradiated for 1 h. Chromatography of the
residue returned starting material (0.012 g, 2%) and gave
1-methyl-3-methoxy-5-pentadecafluoroheptyl-1,2,4-triazole (22a)
(0.165 g 32%) and 10a (0.175 g; 36%). Compound 22a had mp
1
117 °C (from benzene). IR: 3300 cm-1. H NMR (DMSO-d6):
1
35 °C (from light petroleum). H NMR (CDCl3): δ 3.93 (t, 3H,
δ 2.75 (d, 3H, J ) 5.0 Hz), 3.89 (s, 3H), 6.38 (q, 1H, J ) 5.0
Hz). MS: m/z 480 (100) (M+), 452 (25), 410 (19), 161 (73), 119
(28), 69 (30). Anal. Calcd for C11H7F15N4: C, 27.51; H, 1.47;
N, 11.67. Found: C, 27.60; H, 1.60; N, 11.80. Compound 10a
J H-F ) 1.5 Hz), 3.99 (s, 3H). MS: m/z 481 (97) (M+), 410 (14),
162(100), 105(21), 69(22). Anal. Calcd for C11H6F15N3O: C,
27.46; H, 1.26; N, 8.73. Found: C, 27.60; H, 1.40; N, 8.80.
1
had mp 90-91 °C (from light petroleum). IR: 3240 cm-1. H
Ir r a d ia tion of Oxa d ia zole 9b in th e P r esen ce of Tr i-
eth yla m in e (TEA). A solution of 9b (0.2 g; 0.8 mmol) in
methanol (160 mL) apportioned into nine tubes was irradiated
in the presence of an excess of TEA for 1 h; chromatography
returned starting material (0.035 g; 17%) and gave 1-methyl-
3-methoxy-5-heptafluoropropyl-1,2,4-triazole (22b ) (0.035 g;
17%) and 10b (0.075 g; 38%). Compound 22b, isolated as
viscous oil: 1H NMR (CDCl3) δ 3.93 (t, 3H; J ) 1.5 Hz), 3.99
(s, 3H). MS: m/z 281 (100) (M+), 210 (4), 161 (20), 105 (7), 70
(19), 43 (13). Anal. Calcd for C7H6F7N3O: C, 29.91; H, 2.15;
N, 14.95. Found: C, 29.80; H, 2.30; N, 15.10.
NMR (DMSO-d6): δ 2.92 (s, 3H), 8.44 (br s, 1H). MS: m/z 468
(40) (M + 1), 448 (10), 100 (3), 91(28), 69 (33), 58 (100). Anal.
Calcd for C10H4F15N3O: C, 25.71; H, 0.86; N, 9.00. Found: C,
25.90; H, 0.90; N, 9.20.
Ir r a d ia tion of Oxa d ia zole 9b in th e P r esen ce of Meth -
yla m in e. Irradiation of compound 9b (0.15 g; 0.6 mmol) in
the presence of methylamine as before and chromatography
returned starting material (0.023 g; 15%) and gave 1-methyl-
3-N-methylamino-5-heptafluoropropyl-1,2,4-triazole (12) (0.045
g; 27%) and 2-N-methylamino-5-heptafluoropropyl-1,3,4-oxa-
diazole (10b) (0.045 g; 28%). Compound 12 had mp 89-91 °C
Ir r a d ia tion of Oxa d ia zole 9a in Meth a n ol. A sample of
9a (0.2 g; 0.4 mmol) in methanol (160 mL) was apportioned
into nine Pyrex tubes and irradiated for 1 h. Chromatography
of the residue gave 22a (0.075 g; 39%) and compound 23 (0.100
g; 50%), mp 49 °C (from light petroleum). IR: 3325, 3200, 1620
1
(from light petroleum). IR: 3310 cm-1. H NMR (DMSO-d6):
δ 2.69 (d, 3H, J ) 5.1 Hz,), 3.82 (t, 3H, J ) 1.7 Hz), 6.30 (q,
1H, J ) 5.1 Hz). MS: m/z 280 (100) (M+), 252 (24), 210 (33),
161 (28), 119 (24), 69 (26), 42 (37). Anal. Calcd for C7H7F7N4:
C, 30.01; H, 2.52; N, 20.00. Found: C, 30.10; H, 2.60; N, 20.10.
Compound 10b had mp 74-75 °C (from light petroleum). IR:
3220, 3160, 1684 cm-1. IR (CHCl3): 3450, 1640 cm-1. 1H NMR
(DMSO-d6): δ 3.13 (s, 3H), 5.61 (br s, 1H). MS: m/z 267 (51)
(M+), 169 (9), 148 (38), 119 (12), 69 (42), 58 (100), 42 (45). Anal.
Calcd for C6H4F7N3O: C, 26.98; H, 1.51; N, 15.73. Found: C,
27.10; H, 1.60; N, 15.90.
cm-1. IR (CHCl3): 3420, 3240, 1730 cm-1 1H NMR (DMSO-
.
d6): δ 2.81 (d, 3H, J ) 5.3 Hz), 3.72 (s, 3H), 8.20 (br s, 1H),
11.4 (s, 1H). MS: m/z 499 (100) (M+), 453 (15), 169 (8), 130
(20), 100 (10), 69 (28). Anal. Calcd for C11H8F15N3O2: C, 26.47;
H, 1.62; N, 8.42. Found: C, 26.60; H, 1.70; N, 8.50.
After refluxing compound 23 in methanol containing hy-
drochloric acid, GC/MS analysis showed an almost complete
conversion of 23 into 10a .
Ir r a d ia tion of Oxa d ia zole 9a in th e P r esen ce of Am -
m on ia . A sample of compound 9a (0.25 g; 0.5 mmol) in
methanol (250 mL) was apportioned into two series of nine
Pyrex tubes. An excess of methanolic ammonia was added, and
the solution was irradiated for 1 h. Chromatography of the
residue returned starting material (0.025 g; 10%) and gave
3-amino-1-methyl-5-pentadecafluoroheptyl-1,2,4-triazole (13)
(0.05 g; 24%) and 10a (0.07 g; 28%). Compound 13 had mp
Ir r a d ia tion of Oxa d ia zole 24 in th e P r esen ce of Meth -
yla m in e. A sample of compound 24 (0.20 g; 0.40 mmol) in
methanol (160 mL) was irradiated as described above in the
presence of an excess of methylamine. Chromatography of the
residue returned starting material (0.01 g; 5%) and gave
1-propyl-3-N-methylamino-5-pentadecafluoroheptyl-1,2,4-tria-
zole (25) (0.044 g; 22%) and the 2-N-propylamino-5-pentadeca-
fluoroheptyl-1,3,4-oxadiazole (26) (0.10 g; 50%). Compound 25
156 °C (from benzene/light petroleum). IR: 3377, 1647 cm-1
.
1H NMR (DMSO-d6): δ 3.79 (t, 3H, J H-F ) 1.7 Hz), 5.64 (s,
2H). MS: m/z 466 (100) (M+), 447 (14), 148 (41), 104 (10), 69
(20), 43 (18). Anal. Calcd for C10H5F15N4: C, 25.77; H, 1.08;
N, 12.02. Found: C, 25.90; H, 1.20; N, 12.10.
1
had mp 70-72 °C (from light petroleum). IR: 3302 cm-1. H
NMR (DMSO-d6): δ 0.85 (t, 3H, J ) 7.4 Hz), 1.79 (m, 2H),
2.69 (d, 3H, J ) 5.0 Hz), 4.05 (t, 2H, J ) 7.0 Hz), 6.34 (q, 1H,
J ) 5.0 Hz). MS: m/z 509 (100) (M + 1), 466 (16), 141 (15), 58
(13). Anal. Calcd for C13H11F15N4: C, 30.72; H, 2.18; N, 11.02.
Found: C, 30.60; H, 2.10; N, 11.10. Compound 26 had mp 73-
76 °C (from light petroleum). IR: 3246 cm-1. 1H NMR (DMSO-
d6): δ 0.92 (t, 3H, J ) 7.4 Hz), 1.58 (m, 2H), 3.24 (m, 2H),
8.55 (t, 1H, J ) 5.5 Hz). MS: m/z 496 (100) (M + 1), 454 (29),
411 (7), 128 (48), 100 (14), 69 (52), 44(55). Anal. Calcd for
Ir r a d ia tion of Oxa d ia zole 9a in th e P r esen ce of P r o-
p yla m in e. A sample of compound 9a (0.25 g; 0.5 mmol) in
methanol (250 mL) was irradiated as described above in the
presence of an excess of propylamine. Chromatography of the
residue returned starting material (0.048 g; 19%) and gave
1-methyl-3-N-propylamino-5-pentadecafluoroheptyl-1,2,4-tria-
zole (14) (0.053 g; 21%) and 10a (0.110 g; 44%). Compound 14
C
12H8F15N3O: C, 29.11; H, 1.63; N, 8.49. Found: C, 29.20; H,
1
had mp 82-85 °C (from light petroleum). IR: 3315 cm-1. H
1.70; N, 8.60.
NMR (DMSO-d6): δ 0.86 (t, 3H, J ) 7.5 Hz), 1.50 (m, 2H),
3.03 (m, 2H), 3.81 (s, 3H), 6.43 (t, 1H, J ) 5.8 Hz). MS: m/z
508 (27) (M+), 480 (100), 162 (10), 70 (29), 43 (18). Anal. Calcd
for C13H11F15N4: C, 30.72; H, 2.18; N, 11.02. Found: C, 30.80;
H, 2.30; N, 11.10.
Ir r a d ia tion of Oxa d ia zole 9a in th e P r esen ce of P yr -
r olid in e. Irradiation of compound 9a (0.25 g; 0.5 mmol) was
performed as described above in the presence of an excess of
pyrrolidine, and chromatography returned starting material
(0.010 g; 4%) and gave 1-methyl-3-N-pyrrolidyl-5-pentadeca-
fluoroheptyl-1,2,4-triazole (15) (0.062 g; 23%) and 10a (0.133
Ir r a d ia tion of Oxa d ia zole 24 in th e P r esen ce of Tr i-
eth yla m in e (TEA). Irradiation of compound 24 (0.20 g; 0.40
mmol) in methanol (160 mL) was performed as above in the
presence of an excess of TEA and chromatography gave
1-propyl-3-methoxy-5-pentadecafluoroheptyl-1,2,4-triazole (27)
(0.075 g; 37%), and compound 26 (0.075 g; 36%). Compound
27 was isolated as an oil. 1H NMR (CDCl3): δ 0.95 (t, 3H, J )
7.4 Hz), 1.93 (m, 2H), 3.99 (s, 3H), 4.11 (t, 2H J ) 7.3 Hz).
MS: m/z 510 (100) (M + 1), 480 (6), 448 (12), 410 (7), 141 (63),
70 (14), 42 (15). Anal. Calcd for C13H10F15N3O: C, 30.66; H,
1.98; N, 8.25. Found: C, 30.80; H, 1.90; N, 8.40.
4114 J . Org. Chem., Vol. 69, No. 12, 2004

Photochemistry of Fluorinated Heterocyclic Compounds
Ir r a d ia tion of F u r a za n 1a in th e P r esen ce of Meth yl-
a m in e. A sample of compound 1a (0.75 g; 1, 35 mmol) in
methanol (450 mL) was apportioned into nine Pyrex tubes.
An excess of methylamine was added, and the solution was
irradiated for 2 h. The photolyzate was left to stand in the
dark for 24 h, and the solvent was removed. Chromatography
returned starting material (0.030 g; 4%) and gave 3-N-
methylamino-5-pentadecafluoroheptyl-1,2,4-oxadiazole 9a (0.265
g; 42%), mp 59-60 °C (from light petroleum), lit.6 mp 59-60
°C, and compounds 11 (0.11 g; 17%), and 10a (0.16 g; 25%).
Ir r a d ia tion of F u r a za n 1b in th e P r esen ce of Meth yl-
a m in e. A sample of compound 1b (0.5 g; 1.4 mmol) in
methanol (300 mL) was apportioned into seven Pyrex tubes.
An excess of methylamine was added, and the solution was
irradiated for 3 h. Chromatography gave 3-N-methylamino-
5-heptafluoropropyl-1,2,4-oxadiazole 9b (0.032 g; 9%), mp 50-
52 °C, lit6 mp 50-52 °C, and compounds 12 (0.04 g; 10%) and
10b (0.18 g; 49%).
Cr ysta llogr a p h y. Crystal data for compound 11: C11H7-
N4F15, Mr ) 480.2; orthorhombic, space group Pbca, a ) 11.212-
(5), b ) 10.022(5), c ) 30.647(5) Å, V ) 3444(2) Å3, Z ) 8,
Dc ) 1.852 g cm-3, F(000) ) 1888, µ (Cu KR) ) 2.127 mm-1
;
colorless crystal (0.5 × 0.6 × 0.7 mm3). Diffraction data were
collected on a diffractometer with graphite monochromated (Cu
KR) radiation (λ ) 1.54179 Å), using θ/2θ scan technique. Unit
cell parameters were determined using 58 reflections in the
range 4.9° e θ e 25.3°. A total of 3676 reflections (2840 unique,
Rint ) 0.044) were collected at room temperature in the range
2.88° < θ < 68°. No intensity decay was observed during the
data collection. The structure was solved by direct methods
(SIR97)30 and refined by full-matrix least-squares on F2
(SHELXL97)31 with anisotropic temperature factors for non-H
atoms, for 274 parameters. The perfluoroalkyl chain exhibits
disorder that increases toward the end of the tail, such that
any attempt to split the involved carbon and fluorine atoms
into well-defined positions failed. The final stage converged
to R ) 0.1192 for 1975 observed reflections, with I g 2σ(I),
and R ) 0.144 for all unique reflections after merging. The
final difference map showed a maximum and a minimum
residual peaks of 0.933 and -0.553 e Å-3, respectively, near
the disordered chain atoms.
Crystal data for compound 30a : C4H4F3N3O, Mr ) 167.1;
monoclinic, space group P21/c, a ) 8.703(5), b ) 19.702(5), and
c ) 8.968(4) Å, â ) 115.33(5)°, V ) 1390(1) Å3, Z ) 8, Dc )
1.597 g cm-3, F(000) ) 672, µ (Cu KR) ) 1.542 mm-1, colorless
crystal (0.4 × 0.5 × 0.8 mm3). Diffraction data were collected
on a diffractometer with graphite monochromated (Cu KR)
radiation (λ ) 1.54179 Å), using θ/2θ scan technique. Unit cell
parameters were determined using 52 reflections in the range
5.8° e θ e 30.1°. Two independent molecules are contained in
the unit cell. Under the X-ray beam, the crystal showed
considerable degradation and an intensity decay up to 60%
was observed in the standard reflections. Therefore, data
collection was interrupted at a completeness of 66.8%. and a
linear decay correction was applied during data reduction
(Siemens, 1994). A total of 2264 reflections (1689 unique,
Rint ) 0.0579) were collected at room temperature in the range
4.48° < θ < 67.9°. Despite the incomplete data collection, the
structure was well solved by direct methods (SIR97)30 and
refined by full-matrix least-squares on F2 (SHELXL97).31 Due
to the presence of the two independent molecules in the unit
cell and to the uncompleted data collection, the last refinement,
with anisotropic temperature factors for non-H atoms, was
separately carried out on each molecule. The final stage, for
193 parameters, converged to R ) 0.0634 for 1449 observed
reflections, with I g 2σ(I), and R ) 0.0695 for all unique
reflections after merging. The final difference map showed a
maximum and a minimum residual peaks of 0.3431 and
-0.296 e Å-3, respectively.
Ir r a d ia tion of F u r a za n 28 in th e P r esen ce of Meth yl-
a m in e. A sample of compound 28 (0.5 g; 1.9 mmol) in
methanol (400 mL) was apportioned into nine Pyrex tubes.
An excess of methylamine was added, and the solution was
irradiated for 3 h. Chromatography gave 1-methyl-3-N-meth-
ylamino-5-trifluoromethyl-1,2,4-triazole 31a (0.05 g; 15%) and
2-N-methylamino-5-trifluoromethyl-1,3,4-oxadiazole 30a (0.100
g; 32%). Compound 31a had mp 68-70 °C (from light petro-
leum). IR: 3304 cm-1 1H NMR (DMSO-d6): δ 2.69 (d, 3H,
.
J ) 4.9 Hz), 3.81 (s, 3H), 6.22 (q, 1H, J ) 4.9 Hz). MS: m/z
180 (55) (M+), 161(10), 152 (15), 110 (20), 69 (18), 59 (20), 43
(100). Anal. Calcd for C5H7F3N4: C, 33.34; H, 3.92; N, 31.10.
Found: C, 33.40; H, 3.80; N, 31.20. Compound 30a had mp
102-104 °C (from light petroleum). IR: 3235, 3170, 1680,
cm-1; IR (CHCl3): 3450, 1640 cm-1 1H NMR (DMSO-d6): δ
.
2.92 (s, 3H), 8.35 (br s, 1H). MS: m/z 167 (100) (M+), 137 (8),
110 (13), 69 (77), 58 (96). Anal. Calcd for C4H4F3N3O: C, 28.75;
H, 2.41; N, 25.15. Found: C, 28.90; H, 2.50; N, 25.30.
Irradiation of 28 (0.5 g; 1.9 mmol) in methanol (400 mL) in
the presence of an excess of methylamine (molar ratio 3/1) for
1.5 h, followed by a careful workup procedure including
standing the photolyzate for 24 h in the dark, careful removal
of the solvent, and chromatography allowed to isolate 3-N-
methylamino-5-trifluoromethyl-1,2,4-oxadiazole 29a (0.032 g;
10%), together with amounts of starting material and com-
pounds 30a and 31a . Analytical determinations of the pho-
tolyzate (GC/MS) gave: starting material 20%, 29a (50%), 30a
(15%), 31a (15%). Analytical irradiations of 29a in the presence
of methylamine gave 30a and 31a (GC/MS). Compound 29a
had mp 37 °C (from light petroleum). IR: 3290, 3120 cm-1
.
1H NMR (DMSO-d6): δ 2.81 (d, 3H, J ) 5 Hz), 7.49 (br s, 1H).
MS: m/z 167 (100) (M+), 147 (18), 139(20), 95 (22), 69 (95), 55
(48), 42 (85). Anal. Calcd for C4H4F3N3O: C, 28.75; H, 2.41;
N, 25.15. Found: C, 28.80; H, 2.30; N, 25.20.
Ack n ow led gm en t. Financial support from Italian
MIUR and University of Palermo within the National
Research Project “Fluorinated Compounds: New Ma-
terials for Advanced Applications” is gratefully acknowl-
edged.
Ir r a d ia tion of F u r a za n 28 in th e P r esen ce of P r op yl-
a m in e. A sample of compound 28 (0.5 g; 1.9 mmol) in
methanol (400 mL) was apportioned into nine Pyrex tubes.
An excess of propylamine was added, and the solution was
irradiated for 3 h. Chromatography of the residue returned
starting material (0.05 g; 10%) and gave 1-propyl-3-N-propyl-
amino-5-trifluoromethyl-1,2,4-triazole (31b) (0.12 g; 27%) and
2-N-propylamino-5-trifluoromethyl-1,3,4-oxadiazole (30b) (0.12
Su p p or tin g In for m a tion Ava ila ble: Full details of the
X-ray structures of compounds 11 and 30a , including ORTEP
drawings of the molecules, packing diagrams, complete tables
of crystal data, atomic coordinates, bond lengths and angles,
torsion angles and anisotropic displacement parameters. This
material is available free of charge via the Internet at
http://pubs.acs.org.
g; 32%). Compound 31b was isolated as an oil. IR: 3320 cm-1
.
1H NMR (CDCl3): δ 0.94 (m, 6H), 1.60 (m, 2H), 1.86 (m, 2H),
3.20 (m, 2H), 4.02 (t, 2H, J ) 7.3 Hz), 4.35 (br s, 1H). MS:
m/z 236 (21) (M+), 207 (100), 165 (94), 145 (19), 69 (3), 41 (27).
Anal. Calcd for C9H15F3N4: C, 45.76; H, 6.40; N, 23.72.
Found: C, 45.90; H, 6.50; N, 23.80. Compound 30b had mp
52 °C (from light petroleum). IR: 3215, 3160, 1670 cm-1. IR-
(CHCl3) 3440, 1635 cm-1. 1H NMR (CDCl3): δ 0.99 (t, 3H, J )
7.4 Hz), 1.70 (m, 2H), 3.38 (m, 2H), 6.37 (br s, 1H). MS: m/z
195 (42) (M+), 166(71), 153 (100), 137 (68), 126 (79), 118 (51),
69 (92), 41 (89). Anal. Calcd for C6H8F3N3O: C, 36.93; H, 4.13;
N, 21.53. Found: C, 36.80; H, 4.20; N, 21.40.
J O049814E
(30) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.; Spagna,
R. SIR97: A New Tool for Crystal Structure Determination and
Refinement. J . Appl. Cryst. 1999, 32, 115-119.
(31) Sheldrick, G. M. SHELXL-97, Release 97-2; University of
Go¨ttingen: Germany, 1997.
J . Org. Chem, Vol. 69, No. 12, 2004 4115