New perspectives in oxazole chemistry: Synthesis and cycloaddition reactions of a 4-nitro-2-phenyl derivative

Full text of DOI:10.1021/jo9608580

J . Org. Chem. 1996, 61, 7933-7936
7933
Notes
conditions. Bearing in mind that the starting material
was prepared by treatment of the corresponding 5-meth-
oxycarbonyl derivative with concentrated HCl,8 it ap-
peared reasonable to account for the original results by
adventitious acid catalysis. Indeed, when 1 was heated
in xylene at 155 °C with a trace amount of the same acid,
4-nitro-2-phenyloxazole 5 was isolated in 29% absolute
yield.9
Nitrogen protonation probably favors the cleavage of
both N-O and C-C bonds in the intermediates 2 and 3,
respectively, and the resulting nitrile ylide 4 is now able
to convert into 5 despite the presence of the NO2 group
(Scheme 1).
New P er sp ectives in Oxa zole Ch em istr y:
Syn th esis a n d Cycloa d d ition Rea ction s of a
4-Nitr o-2-p h en yl Der iva tive1
Rodolfo Nesi,* Stefania Turchi,* and Donatella Giomi
Dipartimento di Chimica Organica “Ugo Schiff”-Centro di
Studio del CNR sulla chimica e la struttura dei composti
eterociclici e loro applicazioni, Universita` di Firenze, Via
Gino Capponi 9, I-50121 Firenze, Italy
Received May 9, 1996
In tr od u ction
The same electron-withdrawing substituent enabled
the oxazole system to participate as a dienophile in
normal [2 + 4] cycloaddition processes. Treatment of 5
with an excess of 2,3-dimethylbuta-1,3-diene (DMB) (6)
in chloroform at 110 °C afforded predominantly the
dihydrobenzoxazole 8 through the labile adduct 7, to-
gether with a minor amount of compound 9 that could
be easily obtained from 8 and 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ) (Scheme 2).
The nitro derivative 5 was found to react even at 40
°C both with cyclopentadiene (10) and 6,6-dimethylful-
vene (13), leading in good yields to mixtures of the
diastereomeric tricyclic systems 11 and 12, and 14 and
15, respectively (Scheme 3). The former compounds were
smoothly separated in chromatography, but efforts to
isolate the more strained species 14 and 15 as pure
products failed, due to their tendency to undergo retro
Diels-Alder reactions.
Whereas 4-nitroisoxazoles have been extensively in-
vestigated over the past century,2 the corresponding
oxazole derivatives remained practically unexplored in
the same period,3 probably due to the discouraging
results achieved by different synthetic approaches. Since
the 4-position of this heterocycle is quite resistant to
direct electrophilic nitration,4 a mercuration-iodination
sequence followed by treatment of the resulting 4-halo
derivative with nitrogen tetraoxide was examined with
2-methyl-5-phenyl- and 2-methyl-5-(p-chlorophenyl)oxa-
zole, but the desired nitro compounds were obtained in
4-5% yields.5 On the other hand, although thermal
isoxazole isomerization represents a well established and
attractive entry into the oxazole system,6 flash vacuum
pyrolysis (FVP) of some 5-alkyl-3-methyl-4-nitro deriva-
tives afforded only 1-cyano-1-nitroacetone in quantitative
yields.7
In order to probe if this latter disappointing finding
can be ascribed to the peculiar acidic properties of the
substituents at position 5 rather than to a retarding effect
of the NO2 group on the ring closure of the intermediate
nitrile ylide,7 we decided to explore the FVP chemistry
of 4-nitro-3-phenylisoxazole 1.
Increasingly forcing conditions were required with
cyclohexa-1,3-diene (16) and 2-pyrone (19), giving com-
parable amounts of 17 and 18 (overall yield 63%) and
2-phenylbenzoxazole (21) in 25% yield, respectively. The
formation of the latter compound can be explained by a
concomitant loss of carbon dioxide and nitrous acid from
unstable primary adducts of type 20 (Scheme 4).10
In order to test the possibility of exploiting 5 for a new
synthetic approach to oxazolopyridines, this species was
allowed to react with 1-(dimethylamino)-3-methyl-1-
azabuta-1,3-diene (22). As a result of a [2 + 4] cycload-
dition process followed by elimination of nitrous acid and
dimethylamine from the labile intermediate 23, 6-methyl-
2-phenyloxazolo[4,5-b]pyridine (24) was obtained in 30%
yield (Scheme 5).
A quite different reaction course was observed on going
from 22 to the uracil 25, previously employed as a
2-azadiene partner with electrophilic alkenes,11 and we
isolated the pyridopyrimidine system 28 in 67% yield.
Ring-opening of the oxazoline moiety of the Michael
adduct 26 now gives rise to the polyfunctionalized
derivative 27 that leads to 28 by a 6π-electron cyclization,
followed by elimination of nitrous acid (Scheme 6).
Resu lts a n d Discu ssion
Attempts to obtain the 4-nitrooxazole 5 by FVP of 1
under different conditions were completely unsuccessful.
Isoxazole 1 was recovered unchanged at 425 °C (1 Torr),
and its progressive decomposition was observed at 550-
700 °C (10-2 Torr) without any appearance of the desired
product. In contrast, prolonged heating of the same
compound in boiling anisole (170 °C) afforded 5 in 35-
40% yields.1 Interestingly, this isomerization vanished
for repeated experiments on more and more purified
samples of 1, that were substantially stable under these
(1) For a preliminary communication on a part of this work, see:
Nesi, R.; Turchi, S.; Giomi, D.; Papaleo, S. J . Chem. Soc., Chem.
Commun. 1993, 978.
(2) (a) Boyer, J . H. Nitroazoles. The C-Nitro Derivatives of Five-
membered N- and N,O-Heterocycles; Feuer, H., Ed.; VHC Publishers:
New York, 1986; Chapter 5. (b) Gru¨nanger, P.; Vita-Finzi, P. Isoxazoles,
The Chemistry of Heterocyclic Compounds; Taylor, E. C., Ed.; Wiley-
Interscience: New York, 1991; Vol. 49, Part 1, Chapter 1.
(3) Reference 2a, p 340.
(4) Turchi, I. J . Oxazoles, The Chemistry of Heterocyclic Compounds;
Turchi, I. J ., Ed.; Wiley-Interscience: New York, 1986; Vol. 45, p 103.
(5) Hammar, W. J .; Rustad, M. A. J . Heterocycl. Chem. 1981, 18,
885.
(8) Nesi, R.; Giomi, D.; Turchi, S.; Tedeschi, P.; Ponticelli, F. Gazz.
Chim. Ital. 1993, 123, 633.
(9) Attemps to improve this value at the expense of the recovered
nitroisoxazole 1 (Experimental Section) by longer reaction times failed,
due to increased decomposition processes.
(10) The regiochemistry of these intermediates is arbitrarily por-
trayed.
(6) Reference 2b, p 285.
(7) Perez, J . D.; Wunderlin, D. A. J . Org. Chem. 1987, 52, 3636.
(11) Walsh, E. B.; Nai-J ue, Z.; Fang, G.; Wamhoff, H. Tetrahedron
Lett. 1988, 29, 4401.
S0022-3263(96)00858-4 CCC: $12.00 © 1996 American Chemical Society

7934 J . Org. Chem., Vol. 61, No. 22, 1996
Notes
Sch em e 1
Sch em e 4
Sch em e 2
Sch em e 5
Sch em e 3
Sch em e 6
Finally, treatment of 5 with diphenylnitrilimine (29)
at room temperature afforded compound 31 in 49% yield
through a regioselective 1,3-dipolar cycloaddition involv-
ing a primary adduct 30 that suffers from extrusion of
nitrous acid (Scheme 7).
unequivocal N-methyl derivative.13 The relative stereo-
chemistry of the endo adducts 11, 14, and 17 and the
exo isomers 12, 15, and 18 was inferred by a careful
analysis of the shape of the H-2 resonance in the range
δ 5.15-5.65 (Experimental Section). In particular, as a
Whereas the regiochemistry of the bicyclic compound
24 was firmly established on the basis of the available
13C NMR data for the different oxazolopyridine systems,12
the stucture of 31 was suggested by comparison of the
13C NMR spectrum with that of the corresponding
(12) Chimichi, S.; Tedeschi, P.; Nesi, R.; Ponticelli, F. Magn. Reson.
Chem. 1985, 23, 86.
(13) Cecchi, L.; Melani, F.; De Sio, F. J . Heterocycl. Chem. 1985,
22, 951.

Notes
J . Org. Chem., Vol. 61, No. 22, 1996 7935
indicated, the reactions of the nitrooxazole 5 were carried out
in a screw-capped tube (Pyrex No. 13) on 1 mmol scale in the
specified solvent (1 mL); magnetic stirring was adopted for those
experiments performed at room temperature.
Sch em e 7
4-Nitr o-2-p h en yloxa zole (5). A solution of the nitroisox-
azole 1 (0.190 g, 1 mmol) in xylene (3 mL) containing a catalytic
amount of concentrated aqueous HCl (37%, 2-3 µL) was heated
in a screw-capped tube (Pyrex No. 18) at 155 °C for 72 h. The
brown residue was subjected to flash chromatography with
toluene/ligroin (3:1 v/v) as eluent. After the unreacted 1 was
recovered from the faster moving band (Rf ) 0.48, 0.057 g), the
slower one afforded compound 5 (Rf ) 0.28, 0.056 g, 29%) that
was crystallized from n-pentane as ivory-colored needles: mp
153-154 °C; IR 3163, 1608, 1561, 1513, and 1377 cm-1; 1H NMR
δ 7.45-7.60 (m, 3H), 8.06-8.12 (m, 2H), 8.50 (s, 1H); 13C NMR
δ 125.15 (s), 127.0 (d), 129.1 (d), 132.2 (d), 137.7 (d), 149.4 (s),
161.5 (s). Anal. Calcd for C9H6N2O3: C, 56.85; H, 3.18; N, 14.73.
Found: C, 57.04; H, 3.22; N, 14.55.
Cycloa d d ition Rea ction s of 5 w ith th e Dien es 6, 10, a n d
16: Syn th esis of Com p ou n d s 8, 9, 11, 12, 17, a n d 18.
Gen er a l P r oced u r e. A mixture of 5 and the reagent (5 mmol)
in CHCl3 was heated at the temperature indicated in the
schemes until the starting material was completely consumed
(TLC, 1H NMR). The residue was resolved into two components
by flash chromatography with toluene as eluent.
A. The first band gave 5,6-dimethyl-2-phenylbenzoxazole (9)
as a white solid (Rf ) 0.34, 0.030 g, 13%): mp 161-162 °C [after
sublimation at 65-70 °C (10-2 Torr)]; IR 3059, 3030, 1620, 1585,
and 1549 cm-1 1H NMR δ 2.37 (s, 3H), 2.39 (s, 3H), 7.36 (s,
;
1H), 7.48-7.55 (m, 4H), 8.20-8.27 (m, 2H); 13C NMR δ 20.2 (q),
20.6 (q), 110.85 (d), 120.0 (d), 127.0 (s), 127.4 (d), 128.8 (d), 131.1
(d), 133.3 (s), 134.3 (s), 140.2 (s), 149.4 (s), 162.3 (s). Anal. Calcd
for C15H13NO: C, 80.69; H, 5.97; N, 6.27. Found: C, 80.46; H,
6.04; N, 5.97.
F igu r e 1.
The slower moving fractions yielded 4,7-dihydro-5,6-dimethyl-
2-phenylbenzoxazole (8) (Rf ) 0.17, 0.160 g, 71%) that was
crystallized from 30-50 °C petroleum ether as colorless
needles: mp 148-148.5 °C; IR 3059, 3036, 1686, 1646, and 1546
1
cm-1; H NMR δ 1.79 (s, 6H), 3.25 (m, 4H), 7.39-7.48 (m, 3H),
7.98-8.05 (m, 2H); 13C NMR δ 19.15 (q), 19.25 (q), 29.9 (t), 31.9
(t), 121.9 (s), 124.3 (s), 125.9 (d), 127.9 (s), 128.6 (d), 129.7 (d),
132.8 (s), 144.5 (s), 159.95 (s). Anal. Calcd for C15H15NO: C,
79.97; H, 6.71; N, 6.22. Found: C, 80.00; H, 6.82; N, 6.06.
B. The faster running band afforded (2SR,6SR)-6-nitro-4-
phenyl-3-oxa-5-azatricyclo[5.2.1.02,6]deca-4,8-diene (11) as ivory-
colored crystals (Rf ) 0.25, 0.049 g, 19%): mp 70-71 °C (from
30-50 °C petroleum ether); IR 3080, 2998, 1631, 1578, 1534,
F igu r e 2.
consequence of different dihedral angles between the H-1
and H-2 protons, the corresponding J 1,2 values increased
(1.0 Hz vs 4.5 Hz) on going from the nitro derivatives 11
and 14 to 12 and 15, respectively. On the other hand,
COSY experiments on 11 and 17 clearly showed, al-
though to a different extent, a diagnostic interaction of
the endo H-2 with the bridge methylene H-b10 proton.
In conclusion, a practical route to a 4-nitrooxazole
system 5 was devised for the first time, based on the acid-
catalyzed thermal isomerization of the corresponding
isoxazole derivative 1. The former compound behaves
both as a dienophile and a dipolarophile toward different
4π counterparts and, in some instances, it can be formally
regarded as a synthetic equivalent of the hetaryne 32
for direct carbo- and heteroannulations of the oxazole ring
through tandem cycloaddition-elimination processes.
and 1350 cm-1 1H NMR δ 1.73 (br, d, J ) 10.2 Hz, 1H), 1.90
;
(dq, J ) 10.2 and 2.0 Hz, 1H), 3.34-3.40 (m, 1H), 3.51-3.56
(m, 1H), 5.20 (dd, J ) 2.0 and 1.0 Hz, 1H), 6.22 (dd, J ) 5.7 and
3.0 Hz, 1H), 6.30 (dd, J ) 5.7 and 2.8 Hz, 1H), 7.40-7.60 (m,
3H), 7.98-8.03 (m, 2H); 13C NMR δ 43.7 (t), 47.9 (d), 49.5 (d),
87.2 (d), 119.0 (s), 125.9 (s), 128.6 (d), 129.1 (d), 132.95 (d), 135.5
(d), 137.2 (d), 171.0 (s). Anal. Calcd for C14H12N2O3: C, 65.62;
H, 4.72; N, 10.93. Found: C, 65.34; H, 4.79; N, 10.66.
The second one gave (2RS,6RS)-6-nitro-4-phenyl-3-oxa-5-
azatricyclo[5.2.1.02,6]deca-4,8-diene (12) as a colorless oil (Rf )
0.20, 0.169 g, 66%): an analytical sample was obtained by
dissolution in 30-50 °C petroleum ether, filtration, evaporation
to dryness, and prolonged evacuation at room temperature (10-2
Torr); IR (liquid film) 3072, 1630, 1600, 1577, 1544, and 1350
cm-1; 1H NMR δ 1.78 (br d, J ) 10.2 Hz, 1H), 1.90 (dt, J ) 10.2
and 1.7 Hz, 1H), 3.41-3.48 (m, 1H), 3.82-3.88 (m, 1H), 5.65 (d,
J ) 4.5 Hz, 1H), 6.08-6.18 (m, 2H), 7.35-7.58 (m, 3H), 7.85-
7.95 (m, 2H); 13C NMR δ 44.3 (t), 45.9 (d), 51.6 (d), 87.6 (d), 121.5
(s), 125.9 (s), 128.5 (d), 128.9 (d), 132.7 (d), 134.2 (d), 136.0 (d),
169.0 (s). Anal. Calcd for C14H12N2O3: C, 65.62; H, 4.72; N,
10.93. Found: C, 65.40; H, 4.94; N, 10.82.
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. Unless otherwise
stated, IR spectra were taken as dispersions in KBr, while 1H
and 13C NMR spectra were recorded in CDCl3 solutions at 200
C. (2SR,6SR)-6-Nitro-2-phenyl-3-oxa-5-azatricyclo[5.2.2.02,6]-
undeca-4,8-diene (17) was obtained from the first fraction as a
white solid (Rf ) 0.22, 0.080 g, 30%): mp 89 °C (from 30-50 °C
petroleum ether); IR 3070, 3057, 1628, 1579, 1546, and 1352
MHz and 50 MHz, respectively. Silica gel plates (Merck F254
)
and silica gel 60 (Merck, 230-400 mesh) were used for TLC and
flash chromatographies, respectively; petroleum ether and li-
groin employed for chromatographic workup refer to the frac-
tions of bp 40-70 °C and 75-120 °C, respectively. The raw
products, obtained by evaporation to dryness under reduced
pressure of the reaction mixtures, were dried over phosphorus
pentoxide. The Rf values of the isolated compounds refer to the
different solvent systems employed as eluents. Unless otherwise
1
cm-1; H NMR δ 1.08-1.39 (m, 2H), 1.54-1.86 (m, 2H), 3.18-
3.27 (m, 1H), 3.61-3.68 (m, 1H), 5.15 (br d, J ) 4.0 Hz, 1H),
6.26 (ddd, J ) 8.1, 6.8, and 1.1 Hz, 1H), 6.46 (ddd, J ) 8.1, 6.2,
and 1.1 Hz, 1H), 7.42-7.62 (m, 3H), 8.01-8.08 (m, 2H); 13C NMR
δ 15.5 (t), 21.0 (t), 34.3 (d), 35.9 (d), 83.8 (d), 116.9 (s), 126.0 (s),
128.6 (d), 129.0 (d), 130.9 (d), 132.95 (d), 134.1 (d), 169.8 (s).

7936 J . Org. Chem., Vol. 61, No. 22, 1996
Notes
Anal. Calcd for C15H14N2O3: C, 66.66; H, 5.22; N, 10.36.
Found: C, 66.75; H, 5.33, N, 10.35.
48 h; chromatographic workup [petroleum ether/ethyl acetate
(3:1 v/v)] of the residue afforded compound 24 (Rf ) 0.22, 0.060
g, 29%) that was crystallized from ether as colorless flakes: mp
The following band yielded (2RS,6RS)-6-nitro-4-phenyl-3-oxa-
5-azatricyclo[5.2.2.02,6]undeca-4,8-diene (18) (Rf ) 0.15, 0.089 g,
33%) that was crystallized from n-pentane as colorless crystals:
mp 114-115 °C; IR 3090, 3070, 3052, 1631, 1578, 1547, and 1351
157-158 °C; IR 3059, 3035, 1611, and 1546 cm-1 1H NMR δ
;
2.51 (t, J ) 0.7 Hz, 3H), 7.51-7.58 (m, 3H), 7.68 (m, 1H), 8.28-
8.33 (m, 2H), 8.42 (m, 1H); 13C NMR δ 18.8 (q), 118.4 (d), 126.6
(s), 127.9 (d), 128.9 (d), 130.4 (s), 132.1 (d), 143.1 (s), 147.3 (d),
154.3 (s), 164.95 (s). Anal. Calcd for C13H10N2O: C, 74.27; H,
4.79; N, 13.32. Found: C, 73.98; H, 4.74; N, 13.32.
1
cm-1; H NMR δ 1.23-1.79 (m, 4H), 3.18-3.27 (m, 1H), 3.60-
3.69 (m, 1H), 5.58 (d, J ) 3.7 Hz, 1H), 6.11-6.26 (m, 2H), 7.35-
7.57 (m, 3H), 7.89-7.98 (m, 2H); 13C NMR δ 19.2 (t), 19.35 (t),
33.7 (d), 37.7 (d), 83.3 (d), 117.3 (s), 125.7 (s), 128.4 (d), 128.9
(d), 130.6 (d), 131.8 (d), 132.7 (d), 169.2 (s). Anal. Calcd for
6-(Ben zoylam in o)-1,3-dim eth yl-7-(dim eth ylam in o)pyr ido-
[2,3-d ]p yr im id in e-2,4(1H,3H)-d ion e (28). A mixture of 5 and
the uracil 2517 (0.63 g, 3 mmol) in CHCl3 was stirred at room
temperature for 96 h; the raw product was subjected to flash
chromatography with ethyl acetate/petroleum ether (3:1 v/v) as
eluent to give compound 28 (Rf ) 0.5, 0.236 g, 67%) that was
crystallized from CHCl3 as white needles: mp 224-225 °C; IR
3487, 3420, 3212, 1694, 1650, and 1639 cm-1; 1H NMR (DMSO-
d6) δ 3.14 (s, 6H), 3.25 (s, 3H), 3.50 (s, 3H), 7.48-7.62 (m, 3H),
7.83 (s, 1H), 7.96-8.05 (m, 2H), 10.11(br s, 1H); 13C NMR (DMSO-
d6) δ 28.0 (q), 29.1 (q), 40.1 (q), 99.6 (s), 115.4 (s), 127.9 (d), 128.8
(d), 132.0 (d), 133.9 (s), 137.6 (d), 148.3 (s), 151.6 (s), 158.3 (s),
160.3 (s), 166.1 (s). Anal. Calcd for C18H19N5O3: C, 61.18; H,
5.42; N, 19.82. Found: C, 60.97; H, 5.73; N, 19.76.
C
15H14N2O3: C, 66.66; H, 5.22; N, 10.36. Found: C, 66.38; H,
5.20; N, 10.34.
Con ver sion of th e Dih yd r o Der iva tive 8 in to 9.
A
mixture of 8 (0.060 g, 0.27 mmol) and DDQ (0.067 g, 0.3 mmol)
in anhydrous benzene (1 mL) was refluxed with stirring for 1 h.
Chromatographic workup [petroleum ether/ethyl acetate (6:1
v/v)] of the brown solid left by evaporation to dryness gave 9 (Rf
) 0.6, 0.057 g, 95%).
Rea ction of 5 w ith 6,6-Dim eth ylfu lven e (13). The raw
product coming from the reaction of 5 with 13 (0.53 g, 0.60 mL,
5 mmol) in CHCl3 at 40 °C for 7 days was subjected to flash
chromatography [petroleum ether/ethyl acetate (10:1 v/v)] to give
a 12:1 mixture of (2SR,6SR)- and (2RS,6RS)-10-isopropylidene-
6-nitro-4-phenyl-3-oxa-5-azatricyclo[5.2.1.02,6]deca-4,8-diene (14
and 15) as a white solid (Rf ) 0.44, 0.156 g, 53%): 1H NMR δ
1.49 (s, 3H), 1.51 (s, 3H), [1.63 (s, 3H)], [1.64 (s, 3H)], 3.82-3.87
(m, 1H), [3.88-3.92 (m, 1H)], 4.01-4.06 (m, 1H), [4.34-4.37 (m,
1H)], 5.22 (d, J ) 1.0 Hz, 1H), [5.52 (d, J ) 4.5 Hz, 1H)], [6.24-
6.27 (m, 2H)], 6.29-6.40 (m, 2H), 7.35-7.58 (m, 3H), 7.88-7.94
(m, 2H); 13C NMR δ 19.5 (q), [19.7 (q)], 20.0 (q), [29.6 (q)], [46.6
(d)], 49.35 (d), [50.9 (d)], 51.5 (d), [86.5 (d)], 86.7 (d), 119.8 (s),
120.3 (s), 126.1 (s), 128.5 (d), 128.7 (d), 132.6 (d), 135.0 (d), 136.25
(d), 160.7 (s), 169.55 (s).14
1,3,5-Tr ip h en yl-1H-p yr a zolo[3,4-d ]oxa zole (31). Triethyl-
amine (0.304 g, 0.42 mL, 3 mmol) was added dropwise to a
solution of 5 and N-phenylbenzoylhydrazonoyl chloride18 (0.69
g, 3 mmol) in anhydrous benzene (4 mL), and the mixture was
stirred at room temperature for 24 h. After removal of the solid
by filtration, the organic solution was evaporated to dryness;
chromatographic workup of the residue with ligroin/toluene (5:4
v/v) as eluent afforded the tricyclic derivative 31 (Rf ) 0.40, 0.165
g, 49%) that was crystallized from acetone as white needles: mp
1
234 °C; IR 3060, 3040, 1599, 1570, and 1538 cm-1; H NMR δ
7.20-7.57 (m, 9H), 8.08-8.32 (m, 6H); 13C NMR (75 MHz) δ
117.7 (d), 125.55 (d), 126.2 (d), 127.2 (d), 127.65 (s), 128.5 (d),
128.8 (d), 128.9 (d), 129.3 (d), 130.6 (s), 131.5 (d), 132.05 (s), 139.1
(s), 139.5 (s), 150.1 (s), 167.8 (s). Anal. Calcd for C22H15N3O:
C, 78.32; H, 4.48; N, 12.45. Found: C, 78.26; H, 4.53; N, 12.67.
Some unreacted 5 was recovered from the slower running
fractions (Rf ) 0.30, 0.030 g).
Cycloa d d ition of 5 w ith 2-P yr on e (19). Compound 5 was
heated with 19 (0.49 g, 0.4 mL, 5 mmol) in xylene at 150 °C for
48 h; the brown residue was purified by flash chromatography
[petroleum ether/ethyl acetate (10:1 v/v)] to give 2-phenylben-
zoxazole (21) as a white solid (Rf ) 0.53, 0.040 g, 21%): mp 101-
102 °C [after sublimation at 50 °C (10-2 Torr)] (lit.15 mp 102
°C).
Ack n ow led gm en t. We wish to thank Mrs. Brunella
Innocenti for the analytical data. Prof. Stefano Chimi-
chi is gratefully acknowledged for running and discuss-
ing the 13C NMR spectra of compound 31.
6-Meth yl-2-p h en yloxa zolo[4,5-b]p yr id in e (24). A mixture
J O9608580
of 5 and 2216 (0.34 g, 3 mmol) in CHCl3 was heated at 55 °C for
(17) Abdulla, R. F.; Brinkmeyer, R. S. Tetrahedron 1979, 35, 1675.
(18) Huisgen, R.; Seidel, M.; Wallbillich, G; Knupfer, H. Tetrahedron
1962, 17, 3. As suggested by a reviewer, the dipole 29 can be more
safely obtained from N-benzoyl-N′-phenylhydrazine and dichloro-
triphenylphosphorane: Wamhoff, H.; Zahran, M. Synthesis 1987, 876.
(14) The values in square brackets refer to the most evident
resonances of the minor diastereoisomer.
(15) Cohen, V. I. J . Heterocycl. Chem. 1979, 16, 13.
(16) Waldner, A. Helv. Chim. Acta 1988, 71, 486.