Competing Ring-Photoisomerization Pathways in the 1,2,4-Oxadiazole Series. An Unprecedented Ring-Degenerate Photoisomerization ‡ Silvestre Buscemi, Andrea Pace, Ivana Pibiri, 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 nvivona@unipa.it Received May 14, 2002 Abstract: The irradiation of some 5-alkyl-3-amino-1,2,4- oxadiazoles at λ ) 254 nm in methanol in the presence of triethylamine (TEA) gave ring-photoisomerization both into 2-alkyl-5-amino-1,3,4-oxadiazoles and, unprecedently, into the ring-degenerate 3-alkyl-5-amino-1,2,4-oxadiazoles. The competing ring contraction-ring expansion route and the internal cyclization-isomerization mechanism explain the results. Ring photoisomerizations of aromatic five-membered heterocycles are well-known reactions and their possible mechanisms have been systematized. 1-6 A theoretical approach also has been evaluated to rationalize these reactions in terms of the relative energies of presumed intermediates and multiplicity of corresponding excited states. 6,7 Among the different mechanisms, two widely observed pathways are represented by (i) the “ring contraction-ring expansion” route, which involves a three-membered-ring intermediate and explains the in- terchange of adjacent ring atoms, and (ii) the “internal cyclization-isomerization” route (also named “electrocy- clic ring closure-heteroatom migration” pathway), which assumes an initial bicyclic species through the formation of a bond between positions 2 and 5 of the rearranging ring, followed by sigmatropic shifts and final ring- isomerization. For a given five-membered heterocycle, competing pathways involving both ring contraction and electro- cyclic ring closure have been documented. 2,3 This is the case, e.g., of pyrazole, 8 oxazole, 9,10 or isothiazole, 11 for which competing pathways were shown to depend on the structure of the starting ring (the nature of substituents and their position), as well as on the photoreaction medium. Interestingly, in the isothiazole series the occurrence of the above competing routes is also affected by addition of TEA to the irradiation medium. 11 As for O-N bond containing azoles, isoxazoles are historically known 2,3,6 to undergo the isoxazole-to-oxazole rearrange- ment via the ring contraction mechanism along azirine intermediates, isolable in some cases. Moreover, 1,2,5- oxadiazoles (furazans) are known to give rearrangements by a photofragmentation pattern. 2,12 In turn, 1,2,4- oxadiazoles undergo photocleavage of the ring O-N bond, and the resulting photolytic species develop into different products depending on their structure, as well as on the irradiation conditions and medium. 12,13 The ring-photo- isomerization of 1,2,4-oxadiazoles into 1,3,4-oxadiazoles appears restricted 14 to oxadiazoles containing an XH moiety at C(3) of the ring and, moreover, favored by addition of a base to the photoreaction medium. 15 Thus, in the irradiation of 3-amino- or 3-methylamino-5-phenyl- 1,2,4-oxadiazoles at λ ) 254 nm in methanol, yields of the ring-isomers 2-amino- or 2-methylamino-5-phenyl- 1,3,4-oxadiazoles increased when irradiations were car- ried out in the presence of TEA. To explain these results, the acidity of the NH moiety at C(3) (at least in the excited state) has been invoked, and a ring contraction- ring expansion mechanism has been suggested. 15 Following our studies on the photochemistry of O-N bond containing azoles, in this note we now report clear evidence for the occurrence of competing ring-photoi- somerization pathways in the 1,2,4-oxadiazole series, and, interestingly, for an unprecedented ring-degenerate process involving interchange between positions 3 and 5 of the oxadiazole ring. Irradiations of the 3-aminooxadiazoles 1a,b at λ ) 254 nm in methanol gave the expected ring isomers 2-amino- 1,3,4-oxadiazoles 2a,b by the ring contraction mecha- nism. However, different results were obtained when the irradiation of compounds 1a,b was carried out in metha- nol containing TEA. In fact, under these conditions, photoconversion of the starting material increased but mixtures of compounds 2 and the ring-degenerate iso- mers 4 were formed. An independent synthesis of com- pounds 4 by ammonolysis 16 of the 5-trichloromethyl ‡ This paper is dedicated to Professor Domenico Spinelli on the occasion of his 70th birthday. (1) Lablache-Combier, A. In Photochemistry of Heterocyclic Com- pounds; Buchardt, O., Ed.; Wiley: New York, 1976. (2) Padwa, A. In Rearrangements in Ground and Excited States; de Mayo, P., Ed.; Academic Press: New York, 1980; Vol. III, p 501. (3) Lablache-Combier, A. In CRC Handbook of Organic Photochem- istry and Photobiology; Horspool, W., Ed.; CRC Press: Boca Raton, FL, 1995; p 1063. (4) D’Auria, M. Internet J. Sci. 1997, 4, 15-26. (5) D’Auria, M. Heterocycles 1999, 50, 1115-1135. (6) (a) D’Auria, M. In Targets in Heterocyclic Systems; Attanasi, O. A., Spinelli, D., Eds.; Societa ` Chimica Italiana: Roma, Italy, 1999; Vol. II, p 233. (b) D’Auria, M. Adv. Heterocycl. Chem. 2001, 79, 41-88. (7) D’Auria, M. J. Org. Chem. 2000, 65, 2494-2498. (8) (a) Baltrop, J. A.; Day, A. C.; Mack, A. 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Chem. 1988, 25, 931-935. (15) Buscemi, S.; Pace, A.; Vivona, N.; Caronna, T. J. Heterocycl. Chem. 2001, 38, 777-780. For excellent work on TEA-assisted ring- phototransposition in the isothiazole series, see also: Pavlik, J. W.; Tongcharoensirikul, P.; French, K. M. J. Org. Chem. 1998, 63, 5592- 5603. 10.1021/jo025934f CCC: $22.00 © 2002 American Chemical Society J. Org. Chem. 2002, 67, 6253-6255 6253 Published on Web 07/19/2002