Chemistry of 5-oxodihydroisoxazoles. Part 18. Synthesis of oxazoles by the photolysis and pyrolysis of 2-acyl-5-oxo-2,5-dihydroisoxazoles

Article abstract of DOI:10.1039/a700134g

N-Acylisoxazol-5-ones lose carbon dioxide under photochemical and thermal conditions affording iminocarbenes which undergo intramolecular cyclisation through the oxygen of the acyl group to give oxazoles. Under photochemical conditions those acylisoxazolones with electron withdrawing groups at C-4 usually give high yields of oxazoles, while those with electron donating groups at C-4 give only poor yields: the reverse is observed under thermal conditions.

Full text of DOI:10.1039/a700134g

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Chemistry of 5-oxodihydroisoxazoles. Part 18.1 Synthesis of
oxazoles by the photolysis and pyrolysis of 2-acyl-5-oxo-2,5-
dihydroisoxazoles
Rolf H. Prager,* Jason A. Smith, Ben Weber and Craig M. Williams
Department of Chemistry, Flinders University of South Australia, GPO Box 2100, Adelaide,
Australia 5001
N-Acylisoxazol-5-ones lose carbon dioxide under photochemical and thermal conditions affording
iminocarbenes which undergo intramolecular cyclisation through the oxygen of the acyl group to give
oxazoles. U nder photochemical conditions those acylisoxazolones with electron withdrawing groups at
C-4 usually give high yields of oxazoles, while those with electron donating groups at C-4 give only poor
yields: the reverse is observed under thermal conditions.
acylation of isoxazol-5(2H)-ones: herein we elaborate our pre-
Introduction
liminary report 27 on the photolytic and pyrolytic conversion of
these species into oxazoles.
There is still no general synthesis of oxazoles that is satisfactory
for the preparation of all substituted analogues.2 The two
earliest methods involve the reaction of amides with α-halo
ketones,3 or the dehydration of α-acylaminocarbonyl com-
pounds.4 However, these reactions are limited in their scope and
are often low yielding. The most general and widely used
method is still that developed by Cornforth and Cornforth,5
and the method reported by Yokoyama et al.6 is essentially a
variant of this procedure. The growing number of marine
derived natural products containing the oxazole,7 bis-oxazole,8
tris-oxazole9 or alkylaminooxazole10 system has revived inter-
est in the development of new synthetic procedures for this ring
system. Most recent methods have utilised a biosynthetic mod-
elled approach, involving oxidation 11–13 of a peptide-derived
oxazoline, although the capture of rhodium carbenoids by
nitriles has also been developed as a good oxazole synthesis.14,15
We have previously pointed out the similarity in the photo-
chemical or thermal loss of nitrogen and carbon dioxide from
triazoles and isoxazol-5-ones respectively16 (Scheme 1), and
Discussion
Photolysis
The photolysis or pyrolysis of N-acylisoxazolones gave oxa-
zoles in yields that were generally superior to those obtained
from the corresponding acyltriazoles where corresponding data
was available, as shown in Table 1. Photolyses of N-acylisoxazol-
5(2H)-ones were carried out at 254 and 300 nm, in a variety of
solvents. While formation of oxazoles was fast in acetonitrile at
254 nm, the cleanest products were formed in acetone at 300
nm, and these conditions have been most widely used in this
work. N-Acylisoxazolones with an ester group at C-4 were effi-
ciently photolysed to the corresponding oxazoles, many of
which had not previously been prepared. Both 2-alkyl- and 2-
aryl-oxazoles were readily prepared although the synthesis of
the corresponding 4-nitrophenyl analogue was unsuccessful,
presumably because of predominant light-absorption by this
group. The photolysis of the (pyrrol-2-ylcarbonyl)isoxazolone 3
shows the selectivity of the cyclisation, as the intermediate
iminocarbene could conceivably be captured by the nitrogen of
the pyrrole to give a pyrazine, or by C-3 of the pyrrole to give a
pyridone derivative (Scheme 2). In fact, the oxazole 4 was the
only product isolated and was identified by its spectral
properties.
O
R1
O
R1
R1
O
R2
R3
N
R2
R3
N
N
–CO2
–N2
O
N
R3
N
R2
O
1
The success of the photolysis of derivatives with an ester
group at C-3 depended on the nature of the N-acyl group. The
N-acetyl derivative did not react at 300 nm, but photolysed rap-
idly at 254 nm to give the oxazole in 40% yield (80% based on
consumed starting material): longer photolysis led to decom-
position of the oxazole, and the benzoyl derivative gave similar
results. Likewise, the photolysis of acylated 3-phenyl- and 3-
methyl-isoxazolones gave dramatically reduced yields of the
corresponding oxazoles which were accompanied by fragmen-
tation products, including amides and nitriles. The photolysis
of acylated benzisoxazolones at either 254 or 300 nm gave
no identifiable products. The presence of halogen atoms at
C-4 also decreased the synthetic value of photolysis. Thus the
benzoylated isoxazolone 5 gave the expected oxazole 6, accom-
panied by numerous by-products, of which only the isomeric
oxazole 7 was identified (Scheme 3). Oxazole 7 probably arises
by rearrangement of the intermediate iminocarbene, presum-
ably via the 1H-azirine intermediate (Scheme 4). This rearrange-
ment of iminocarbenes has previously been reported to occur in
R1
O
R3
N
R2
2
Scheme 1
have pyrolysed 17 or photolysed 18 the latter to produce a variety
of heterocycles including imidazoles and pyrimidines. Extrapo-
lation of this mechanism suggests N-acylated isoxazolones
would give oxazoles (Scheme 1), although the photolysis19 and
thermolysis20,21 of N-acyltriazoles appear to lead mainly to
diradicals,22–25 giving rather poor support for this hope. How-
ever, Williams26 has recently reported a new procedure for the
thermal conversion of a number of acyltriazoles to oxazoles in
good yields, although the procedure appears to be capable of
variation only in the substituent at C-2.
In our accompanying paper 1 we report our study of the N-
J. Chem. Soc., Perkin Trans. 1, 1997
2665

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Table 1 Synthesis of oxazoles 2 from 2-acylisoxazol-5(2H)-ones 1
O
Ph
O
O
R1
R2
R3
Yield (%)a
Ph
Me
Me
Br
Ph
Br
N
+
O
N
N
Me
H
H
H
H
H
H
H
H
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
Me
Me
Me
Me
Me
Me
Me
Me
A 10; C 65
B 81
C 88
C 72
C 70
C 79
C 77
C 79
C 80
Br
Me
Pri
O
PhCH2
PhCH2CH2
Ph
2-ClC6H4
4-ClC6H4
2-MeOC6H4
4-MeOC6H4
Pyrrol-2-yl
5
6
7
Scheme 3
O
Ph
Ph
O
Ph
O
Ph
O
H
H
Me
Ph
N
B 30; C 30
C 30
N
Ph
N
H
N
O
Ph
Me
Ph
H
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
A 95; B 40
A 95; B 40; C 35
A 45; C 61
A 32; C 26
A 18
A 56
A 50
E
H
Ph
Ph
O
2,5-Me2-oxazol-4-yl
2,5-Ph2-oxazol-4-yl
CHCl2
CO2Me
CO2Et
2-[6-(Oxazol-2-yl)-
pyridin-2-yl]
O
O
O
Ph
Ph
Ph
Ph
N
N
N
Ph
Ph
4-CO2Et-5-Me-oxazol-
CO2Et
Me
A 8
Scheme 4
2-yl
Phth-CH2 D a
Me
Ph
Me
Ph
Ph
Ph
Me
CO2Et
Ph
Ph
benzo
benzo
Me
Me
H
H
B 80; C 90
A 95; C 29
A 60; C 24
A 95; B, C 0
A 95; B, C 0
A 95; C 24
F 15
of the triplet quenchers or sensitisers, 9-methylanthracene and
benzophenone, had no effect on the photolysis yields.
Due to increased interest in natural products which contain
an oxazole or polyoxazole moiety, we investigated the appli-
cation of this method to the synthesis of oxazoles of this type.
The photolysis of (2-oxazolecarbonyl)isoxazolone 8 gave the
H
Br
H
Me
Me
A 95
Ph
Me
Ph
CF3
MeO
EtO
PhO
H
Ph
Ph
Ph
CO2Et
CO2Et
CO2Et
H
A 80
A 95
A 70
A 50
A 66
A 31
A 64
O
Ph
Ph
H
Me
Me
Me
Me
Me
O
Me
Me
O
N
Me
Me
O
N
O
N
N
N
Me
Me
O
CO2Et
Me
N
N
Me
a
O
(A) Flash vacuum pyrolysis, 490–600 ЊC; (B) photolysis, 254 nm,
CH3CN, silica; (C) photolysis, 300 nm, acetone or CH3CN, Pyrex; (D)
phthalimidomethyl; (E) refer to Experimental section; (F ) photolysis,
300 nm, 1,4-dioxane, pyrex.
O
CO2Et
O
EtO2C
9
10
8
NH2
O
R
C
H
CO2Et
O
N
H
N
11
N
H
O
CO2Et
O
Me
EtO2C
O
O
H2
C
O
N
Me
3
O
N
N
CH2CO
N
O
O
CO2Et
12
O
O
13
N
H
N
CO2Et
bis-oxazole 9 in 61% yield. Following its hydrolysis and conver-
sion to the acid chloride, the bis-oxazole could be used to
acylate a further isoxazolone, leading to the synthesis of the
tris-oxazole 10 (10% overall).
CO2Et
O
A common feature of the peptide derived cyclic polyoxazoles
is the 2-aminoalkyl-5-carboxyoxazole unit similar to 11. We
found that a precursor to this—oxazole 12—could be prepared
in high yield by the photolysis of the appropriate isoxazolone
13 at 300 nm.
N
O
NH
O
N
NH
N
H
CO2Et
H
EtO2C
N
4
Scheme 2
Pyrolysis
the photolysis of 1,2,3-triazoles,28 but is the first example in
which an isomerised oxazole has been isolated from photolysis
of our isoxazolone. None of the photolysis reactions gave
rise to products involving hydrogen abstraction, suggesting that
the intermediate is a singlet iminocarbene and not a triplet
diradical. This is supported by the observation that the presence
Pyrolysis of N-acylisoxazol-5(2H)-ones generally gave poor
results when carried out in a Dowtherm reactor at 250–300 ЊC
or under vacuum in the condensed phase. Flash vacuum
pyrolysis using a 30 cm silica tube filled with silica beads at
500 ЊC gave the best results. In contrast to the observations
with photolysis, those N-acylisoxazolones unsubstituted at C-4
2666
J. Chem. Soc., Perkin Trans. 1, 1997

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and/or with electron withdrawing groups at C-3, which
included benzisoxazolones, were found to give oxazoles in good
yields except with involatile or thermally unstable compounds
as shown in Table 1. In most cases these isoxazolones had either
failed to rearrange under photochemical conditions or gave
poor yields.
Pyrolysis at higher temperatures than 500 ЊC led to formation
of side products. When 14 was pyrolysed at 700 ЊC, 20% of
acetanilide 16 was formed in addition to the oxazole 15, but
none could be detected at 500 ЊC (Scheme 5). Small amounts of
derived from a Meisenheimer rearrangement but by ethylene
elimination from the first formed oxazole 22 (R = Et) (Scheme
7).
O
RO
Me
N
R = Me, Et,
Ph
O
OR
CO2Et
22
CO2Et
Me
N
O
O
O
R = Et
O
Me
O
Me
H2C
H2C
–CH2CH2
N
20
O
Ph
H
21 R = Me, Et, Ph
Me
CO2Et
N
H
+
MeCONHPh
O
N
22
16
Ph
Scheme 7
O
15
14
Me
EtO2C
Ph
O
Scheme 5
Ph
O
N
N
O
the isomeric oxazoles were produced in some cases, particularly
when higher temperatures were used, but it is not certain
whether they were derived from the rearrangement of the N-
acylcarbene or isomerisation of the oxazole (Scheme 4).
O
N
Me
Me
O
N
N
N
N
O
CO2Et
EtO2C
A preliminary investigation has been made of the tolerance
to the pyrolytic reaction conditions of acyl groups substituted
by other than aryl or alkyl groups. While oxamides such as
17 and 18 were readily available, their potential to undergo
decarbonylation before loss of carbon dioxide and oxazole
formation was of interest. In the event, the ethyl ester 17
underwent rearrangement to give oxazole 19 without side reac-
tions. Pyrolysis of the methyl ester 18 gave not only the
expected oxazole 19, but also a small amount of the oxazolone
20, whose origin is suggested to arise from a Meisenheimer
rearrangement 29 (Scheme 6) following a double decarbonyl-
EtO2C
EtO2C
Me
23
Me
24
25
Me
O
OEt
O
R1
R2
CO2Et
H
N
O
N
O
O
O
26
27 R1 = CO2Et, R2 = H
28 R1 = Me, R2 = CO2Et
The polyoxazoles 23–25 were prepared from the respective
isoxazolones. While the yields were low (8–32%) the procedure
has the advantage of being a two step process.
Surprisingly, 2-ethoxycarbonylisoxazolone 26, while formally
very similar to 21 above, decomposed to unidentifiable material,
because of its low volatility. Finally, 2-acetylisoxazolones such
as 27 and 28 lost ketene as the major thermolytic pathway:
fortunately this was not a major problem in their photolytic
reactions.
O
O
OR
O
RO2C
Me
CO2Et
N
O
O
N
Me
CO2Et
19 R = Me, Et
17 R = Et
18 R = Me
In summary, oxazoles are available by a new route from the
decarboxylation of 2-acylisoxazol-5(2H)-ones. Photolysis of
the latter proceeds best when electron withdrawing groups are
present at C-4, whereas flash vacuum pyrolysis is the method of
choice for all other substitution patterns.
–CO
OMe
O
OMe
O
O–
N
MeO
–CO
CO2Et
Me
CO2Et
Me
N
CO2Et
Me
N
O
–O
O
Experimental
O
O
C
General experimental procedures have been described previ-
ously.1 NMR spectra were determined in CDCl3 using SiMe4 as
an internal reference on a Varian Gemini 300 MHz spec-
trometer. Coupling constants J are given in Hz. Light petroleum
refers to the fraction boiling in the range 40–60 ЊC. Photolyses
were conducted in a Rayonet photochemical reactor using
either 300 or 254 nm tubes as stated. Flash vacuum pyrolyses
involved either direct injection or sublimation into a Thermo-
lyne Pyrolyser tube furnace, 30 cm long, packed with silica
beads. Furnace temperature, sublimation temperature, pressure
and time required for completion are shown in parentheses.
Unless otherwise stated, acylisoxazolones were prepared by the
method of Prager et al.1
O
O
O
O
O
O
Me
Me
Me
Me
H
HN
N
N
HC
O
CO2Et
CO2Et
O
CO2Et
20
Scheme 6
ation. This unexpected rearrangement encouraged us to
investigate N-alkoxycarbonylisoxazolones like 21 in the hope
of observing similar rearrangements and it was found that
pyrolysis of the methyl and phenyl carbamates gave only the
corresponding oxazoles 22. However, the ethyl carbamate gave
a mixture of both the expected oxazole and the oxazolone 20
observed above, but in this instance we believe that 20 is not
Ethyl 2-methyloxazole-5-carboxylate 2 (R1 = Me, R2 = H,
R3 = CO2Et)
Photolysis (300 nm, benzene–acetone, 1:9, 15 h) of ethyl 2-
J. Chem. Soc., Perkin Trans. 1, 1997
2667

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acetyl-5-oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave
an oil which was distilled at 55 ЊC/0.02 mmHg (lit.,30 75–
80 ЊC/0.15 mmHg) as a colourless oil (101 mg, 65%) (Found:
Mϩ, 155.0557. Calc. for C7H9NO3: M, 155.0582); δH 1.38 (3
H, t, J 7), 2.56 (3 H, s), 4.38 (2 H, q, J 7) and 7.65 (1 H, s);
δC 14.2, 14.2, 61.3, 134.0, 142.5, 157.7 and 164.7; νmax/cmϪ1
1733, 1589 and 1545; m/z 155 (M, 50%), 127 (80), 110 (43)
and 82 (100).
Flash vacuum pyrolysis of the above isoxazolone (200 mg)
(540 ЊC, 120 ЊC, 0.05 mmHg, 60 min) gave a mixture of the
above oxazole (16 mg, 10%) and ethyl cyanoacetate (102 mg,
90%), whose identities were confirmed by GC–MS.
(2 H, d, J 9), 7.83 (1 H, s) and 8.08 (2 H, d, J 9); δC 14.3, 61.6,
124.9, 128.5, 129.4, 135.3, 138.5, 142,5, 157.8 and 163.3; νmax
/
cmϪ1 1724, 1599 and 1468; m/z 251 (M, 92%), 178 (100) and 139
(40).
Ethyl 2-(2-methoxyphenyl)oxazole-5-carboxylate 2
(R1 = 2-MeOC6H4, R2 = H, R3 = CO2Et)
Photolysis (300 nm, acetone) of ethyl 2-(2-methoxybenzoyl)-5-
oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a crude
product which was distilled as a colourless oil (134 mg, 79%),
bp 102 ЊC/0.1 mmHg, and solidified on cooling to form a white
solid, mp 51–53 ЊC (Found: C, 63.2; H, 5.3; N, 5.7%; Mϩ,
247.0847. C13H13NO4 requires C, 63.15; H, 5.3; N, 5.7%; M,
247.0844); δH 1.42 (3 H, t, J 7), 3.97 (3 H, s), 4.43 (2 H, q, J 7),
6.91–7.37 (2 H, m), 7.52 (1 H, dt, J 8, 2), 7.95 (1 H, s) and 8.10
(1 H, dd, J 8, 2); δC 14.4, 56.1, 61.4, 112.1, 115.4, 120.7, 130.9,
133.0, 135.2, 141.8, 158.1, 158.2 and 162.5; νmax/cmϪ1 1717,
1604, 1580, 1521 and 1491; m/z 247 (M, 60%), 218 (10), 174
(86), 146 (100), 133 (12) and 118 (58).
Ethyl 2-isopropyloxazole-5-carboxylate 2 (R1 = Pri, R2 = H,
R3 = CO2Et)
Photolysis (254 nm. acetonitrile, 2 h) of ethyl 2-(2-methyl-
propionyl)-5-oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg)
gave a product which was distilled to give a colourless oil (131
mg, 81%), bp 40 ЊC/0.05 mmHg (Found: C, 58.9; H, 7.3; N,
7.7%; Mϩ, 183.0896. C9H13NO3 requires C, 59.0; H, 7.2; N,
7.7%; M, 183.0895); δH 1.37 (3 H, t, J 7), 1.40 (6 H, d, J 7), 3.20
(1 H, septet, J 7), 4.40 (2 H, q, J 7) and 7.70 (1 H, s); νmax/cmϪ1
1724, 1599 and 1537; m/z 183 (M, 24%), 168 (8), 155 (12), 138
(6) and 110 (100).
Ethyl 2-(4-methoxyphenyl)oxazole-5-carboxylate 2
(R1 = 4-MeOC6H4, R2 = H, R3 = CO2Et)
Photolysis (300 nm, acetone) of ethyl 2-(4-methoxybenzoyl)-5-
oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a crude
product which was recrystallized from benzene–light petroleum
as a white solid, mp 69–70 ЊC (136 mg, 80%) (Found: C, 63.1; H,
5.2; N, 5.4%; Mϩ, 247.0847. C13H13NO4 requires C, 63.2; H, 5.3;
N, 5.7%; M, 247.0844); δH 1.40 (3 H, t, J 7), 3.88 (3 H, s), 4.42 (2
H, q, J 7), 7.01 (2 H, d, J 9), 7.84 (1 H, s) and 8.13 (2 H, d, J 9);
νmax/cmϪ1 1716, 1605 and 1483; m/z 247 (M, 41%), 174 (55), 152
(36), 146 (60), 135 (72) and 105 (100).
Ethyl 2-benzyloxazole-5-carboxylate 2 (R1 = Bn, R2 = H,
R3 = CO2Et)
Photolysis (300 nm, acetone, 3 h) of ethyl 5-oxo-2-phenylacetyl-
2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a colourless
oil, bp 90 ЊC/0.1 mmHg (148 mg, 88%) (Found: C, 67.8; H, 6.0;
N, 5.9. C13H13NO3 requires C, 67.5; H, 5.7; N, 6.1%); δH 1.37 (3
H, t, J 7), 4.19 (2 H, s), 4.37 (2 H, q, J 7), 7.22–7.39 (5 H, m) and
7.68 (1 H, s); δC 14.3, 34.8, 61.5, 127.5, 128.7, 128.9, 134.0,
134.3, 142.8, 157.8 and 164.4; νmax/cmϪ1 1728, 1590 and 1533;
m/z 231 (M, 61%), 203 (10), 186 (6), 158 (71), 130 (9), 118 (7),
103 (9) and 91 (100).
Ethyl 2-(2-phenylethyl)oxazole-5-carboxylate 2
(R1 = PhCH2CH2, R2 = H, R3 = CO2Et)
Photolysis (300 nm, acetone) of ethyl 5-oxo-2-(3-phenyl-
propionyl)-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a
crude product which was subjected to silica radial chroma-
tography (diethyl ether–light petroleum, 1:4) affording the title
compound (122 mg, 72%) as a pale yellow oil (Found: Mϩ,
245.1049. C14H15NO3 requires M, 245.1052); δH 1.38 (3 H, t, J
7.14), 3.14 (3 H, s), 4.38 (2 H, q, J 7.14), 7.15–7.35 (5 H, m) and
7.65 (1 H, s); δC 14.3, 30.2, 32.8, 61.4, 126.6, 128.3, 128.6, 134.1,
139.8, 142.4, 157.8 and 167.3; νmax/cmϪ1 1733, 1589 and 1538;
m/z 245 (M, 32%), 216 (3), 172 (9), 144 (9) and 131 (3).
Ethyl 2-phenyloxazole-5-carboxylate 2 (R1 = Ph, R2 = H,
R3 = CO2Et)
Photolysis (300 nm, acetone, 3 h) of ethyl 2-benzoyl-5-oxo-2,5-
dihydroisoxazole-4-carboxylate (200 mg) gave an oil which was
crystallised from diethyl ether–light petroleum as white needles
(150 mg, 90%), mp 58–60 ЊC (lit.,30 56 ЊC) (Found: Mϩ,
217.0737. Calc. for C12H11NO3: M, 217.0739); δH 1.42 (3 H, t, J
7), 4.42 (2 H, q, J 7), 7.45–7.58 (3 H, m), 7.85 (1 H, s) and 8.12–
8.18 (2 H, m); δC 14.3, 61.5, 126.4, 127.3, 129.0, 131.7, 135.3,
142.4, 157.9 and 164.2; νmax/cmϪ1 1708, 1574 and 1528; m/z 217
(M, 58%), 189 (14), 172 (10), 144 (84), 122 (47), 116 (64) and
105 (100).
Reactions of 2-benzoyl-3-methylisoxazol-5(2H)-one 1 (R1 = Ph,
R2 = Me, R3 = H)
The isoxazolone (1.8 g, 8.8 mmol) was irradiated in dichloro-
methane (800 ml) for 5 h at 300 nm. Radial silica chrom-
atography (diethyl ether–light petroleum, 3:7) separated the
mixture into three components. Fraction 1 was identified as 4-
methyl-2-phenyloxazole (0.28 g, 27%) by direct comparison
with an authentic sample prepared by the method of Lewy31
(Found: Mϩ, 159.0630. Calc. for C10H9NO: M, 159.0684); δH
2.22 (3 H, d, J 1.25), 7.28–7.44 (4 H, m) and 7.99–8.02 (2 H, m);
Ethyl 2-(2-chlorophenyl)oxazole-5-carboxylate 2 (R1 = 2-ClC6H4,
R2 = H, R3 = CO2Et)
Photolysis (300 nm, acetone) of ethyl 2-(2-chlorobenzoyl)-5-
oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a crude
product which was distilled to afford a colourless oil (134 mg,
79%), bp 100 ЊC/0.05 mmHg (Found: C, 57.5; H, 4.1; N, 5.3%;
Mϩ, 251.0329. C12H10ClNO3 requires C, 57.3; H, 4.0; N, 5.6%;
M, 251.0349); δH 1.41 (3 H, t, J 7), 4.45 (2 H, q, J 7), 7.32–7.67
(3 H, m), 7.93 (1 H, s) and 7.93–8.20 (1 H, m); νmax/cmϪ1 1733,
1583, 1528; m/z 251 (M, 59%), 178 (100) and 123 (24).
δC 11.5, 126.1, 127.5, 128.6, 130.1, 134.2, 137.5 and 161.3; νmax
/
cmϪ1 1603 and 1550; m/z 159 (M, 100%), 130 (50), 104 (32), 90
(83), 77 (39) and 51 (25). Fraction 2 (0.17 g, 12%) was identified
as unreacted starting material. Fraction 3 (0.12 g, 14%) was
identified as benzamide.
Flash vacuum pyrolysis (595 ЊC, 135 ЊC, 0.05 mmHg, 40 min)
of the isoxazolone (100 mg) gave 4-methyl-2-phenyloxazole (74
mg, 95%), isolated as a pale yellow oil, and identical with the
sample prepared above.
Ethyl 2-(4-chlorophenyl)oxazole-5-carboxylate 2 (R1 = 4-ClC6H4,
R2 = H, R3 = CO2Et)
Photolysis (300 nm, acetone) of ethyl 2-(4-chlorobenzoyl)-5-
oxo-2,5-dihydroisoxazole-4-carboxylate (200 mg) gave a crude
product which was distilled to afford a pale yellow oil, bp
110 ЊC/0.05 mmHg, and solidified on cooling to form a white
solid (131 mg, 77%), mp 76–78 ЊC (Found: C, 57.6; H, 4.1; N,
5.4%; Mϩ, 251.0349. C12H10ClNO3 requires C, 57.3; H, 4.0; N,
5.6%; M, 251.0349); δH 1.42 (3 H, t, J 7), 4.42 (2 H, q, J 7), 7.45
Photolysis of 2-benzoyl-4-bromo-3-methylisoxazol-5(2H)-one 1
(R1 = Ph, R2 = Me, R3 = Br)
The isoxazolone 5 (0.5 g, 1.78 mmol) was irradiated in 1,4-
dioxane (200 ml) at 300 nm for 5 h. Separation by silica gel
column chromatography (diethyl ether–light petroleum, 15:85)
2668
J. Chem. Soc., Perkin Trans. 1, 1997

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gave 5-bromo-4-methyl-2-phenyloxazole 6 (0.07 g, 16%) as the
first fraction. The identity was confirmed by direct comparison
with an authentic sample, prepared by bromination of the 4-
methyl-2-phenyloxazole isolated above (Found: Mϩ, 238.9798;
236.9815. C10H8BrNO requires M, 238.9770; 236.9790); δH 2.57
(3 H, s), 7.31–7.64 (3 H, m) and 8.08 (2 H, dd, J 8, 2);
νmax(CDCl3)/cmϪ1 1678 and 1574; m/z 239 (M, 18%), 237 (Mϩ,
20), 211 (33), 209 (39), 170 (41), 168 (41), 130 (100) and 104
(48). The remainder of the material was subjected to reversed
phase HPLC (H2O–CH3CN, 1:4) and GC–MS analysis: 4-
bromo-5-methyl-2-phenyloxazole 7 (ca. 8%) was isolated and
identified by direct comparison with an authentic sample pre-
pared by bromination of the oxazole.32
bp 95 ЊC/0.05 mmHg) (Found: Mϩ, 231.0895. Calc. for
C13H13NO3: M, 231.0905); δH 1.38 (3 H, t, J 7), 2.66 (3 H, s),
4.39 (2 H, q, J 7), 7.42 (3 H, m) and 8.03 (2 H, m); δC 12.1, 14.3,
60.9, 126.4, 126.4, 128.6, 128.6, 130.6, 156.0, 159.5 and 162.3;
νmax/cmϪ1 1716 and 1615; m/z 231 (M, 100%), 203 (31), 186 (10),
158 (29), 130 (90), 104 (71), 77 (49) and 51 (22).
Flash vacuum pyrolysis (170 mg) (540 ЊC, 155 ЊC, 0.05
mmHg, 60 min) gave the oxazole as a straw coloured oil (129
mg, 90%) which was spectroscopically pure.
Ethyl 2,5-dimethyloxazole-4-carboxylate 2 (R1 = R3 = Me,
R2 = CO2Et)
Photolysis (254 nm, acetonitrile, 90 min) of ethyl 2-acetyl-4-
methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate (210 mg)
gave a product which was chromatographed (dichloromethane–
light petroleum, 9:1) to give two fractions which were identified
as unreacted starting material (84 mg, 40%) and ethyl 2,5-
dimethyloxazole-4-carboxylate (67 mg, 40%) by comparison
with authentic samples.4
2-Methyl-4-phenyloxazole 15
Photolysis (300 nm, acetone, 4 h) of 2-acetyl-3-phenylisoxazol-
5(2H)-one 14 (1 g, 4.93 mmol) gave two products which were
separated by silica gel radial chromatography (diethyl ether–
light petroleum, 3:7). The first was identified as the title com-
pound 15 (0.23 g, 29%). The second fraction was identified as
benzonitrile (0.06 g, 11%).
Flash vacuum pyrolysis (350 mg) (595 ЊC, 100 ЊC, 0.05
mmHg, 30 min) gave the oxazole 15, bp 80 ЊC/0.1 mmHg (lit.,33
241 ЊC/760 mmHg), as a straw coloured oil (260 mg, 95%),
identical with a sample prepared by the method of Lewy33
(Found: Mϩ, 159.0689. Calc. for C10H9NO: M, 159.0684); δH
2.49 (3 H, s), 7.27 (1 H, t, J 7), 7.37 (2 H, t, J 7), 7.69 (2 H, d, J
7) and 7.78 (1 H, s); δC 13.9, 125.3, 127.8, 128.6, 131.1, 133.1,
140.7 and 161.8; νmax/cmϪ1 1594 and 1276; m/z 159 (M, 97%),
131 (58), 117 (38), 103 (35), 90 (100), 77 (23), 63 (42) and 51
(31). A white solid (3 mg, 2%) isolated from the pyrolysis tube
was identified as N-phenylacetamide 16 by direct comparison
with an authentic sample.
Ethyl 4-methyl-2-phenyloxazole-5-carboxylate 2 (R1 = Ph,
R2 = Me, R3 = CO2Et)
Photolysis (300 nm, acetonitrile, 45 min) of ethyl 2-acetyl-3-
methyl-5-oxo-2,5-dihydroisoxazole-4-carboxylate (300 mg)
gave a product which was subjected to radial chromatography
(diethyl ether–light petroleum, 15:85) to give two fractions.
The first fraction was an oil which slowly solidified, mp 44–
45 ЊC and was identified as the title compound (88 mg,
35%)36 (Found: Mϩ, 231.0905. Calc. for C13H13NO3: M,
231.0895); δH 1.43 (3 H, t, J 7), 2.56 (3 H, s), 4.42 (2 H, q, J
7), 7.50 (3 H, m) and 8.13 (2 H, dd, J 7, 2); δC 13.5, 14.4,
61.1, 126.4, 127.2, 128.9, 131.5, 137.1, 147.1, 158.9 and 162.2;
νmax/cmϪ1 1716, 1610 and 1543; m/z 231 (M, 100%), 203 (30),
158 (29), 130 (90), 104 (71) and 77 (49). The second fraction
contained a 1:1 mixture of two compounds which could not
be separated or identified.
A mixture of benzamide (200 mg, 1.65 mmol) and ethyl α-
chloroacetoacetate (270 mg, 1.65 mmol) was heated at 140 ЊC
for 2 h. The product was purified by radial chromatography
(diethyl ether–light petroleum, 15:85) to give the title com-
pound (76 mg, 20%) as a straw coloured oil. The spectral data
were identical with those reported above.
2,4-Diphenyloxazole
Photolysis (300 nm, acetone, 4 h) of 2-benzoyl-3-phenyl-
isoxazol-5(2H)-one (0.5 g, 1.89 mmol) gave the title compound
which was purified by radial chromatography (diethyl ether–
light petroleum, 2:3) and recrystallised from benzene–light pet-
roleum as white crystals (100 mg, 24%), mp 101 ЊC.
Flash vacuum pyrolysis (150 mg) (595 ЊC, 155 ЊC, 0.05
mmHg, 60 min) gave a solid which was separated by radial
chromatography (dichloromethane–light petroleum, 35:65) to
give three fractions. The first fraction was recrystallised from
dichloromethane–light petroleum to give colourless needles of
2,4-diphenyloxazole (75 mg, 60%), mp 101–102 ЊC (lit.,33 mp
102–103 ЊC) (Found: Mϩ, 221.0844. Calc. for C15H11NO: M,
221.0841); δH 7.52–7.56 (1 H, m), 7.42–7.51 (5 H, m), 7.82–7.86
(2 H, m), 7.97 (1 H, s) and 8.12–8.16 (2 H, m); δC 125.6, 126.5,
127.5, 128.1, 128.1, 128.8, 130.4, 131.1, 133.4, 142.0 and 161.9;
νmax/cmϪ1 1553 and 1339; m/z 221 (M, 100%), 193 (73), 165 (12),
90 (53), 89 (54), 63 (23) and 51 (15). The second fraction, a
white solid, mp 72–73 ЊC (lit.,34 73 ЊC), was identified as 2,5-
diphenyloxazole (13 mg, 10%) by comparison with an authentic
sample34 (Found: Mϩ, 221.0844. Calc. for C15H11NO: M,
221.0841); δH 7.32–7.53 (7 H, m), 7.72 (2 H, m) and 8.13 (2
H, m); δC 123.4, 124.1, 126.2, 127.4, 128.0, 128.4, 128.8,
128.9, 130.3, 151.2 and 161.1; m/z 221 (Mϩ, 76%), 193 (7),
165 (30), 122 (39), 105 (100), 77 (97) and 51 (52). The third
fraction was identified as N-phenylbenzamide (17 mg, 15%),
mp 156–158 ЊC.
Ethyl 2-(pyrrol-2-yl)oxazole-5-carboxylate 4
Photolysis (300 nm, acetonitrile, 1.5 h) of ethyl 5-oxo-2-(pyrrol-
2-ylcarbonyl)-2,5-dihydroisoxazole-4-carboxylate 3 (240 mg)
gave a product which was purified by radial chromatography
(diethyl ether–light petroleum, 1:1) to give two fractions. The
first fraction was recrystallised from ethanol–water to give the
title compound (59 mg, 30%), mp 136–138 ЊC (Found: Mϩ,
206.0701. C10H10N2O3 requires M, 206.0692); δH 1.40 (3 H, t, J
7), 4.40 (2 H, q, J 7), 6.34 (1 H, m), 7.00 (2 H, m), 7.76 (1 H, s)
and 10.04 (1 H, NH, br s); δC 14.3, 61.4, 111.0, 113.1, 119.3,
122.9, 134.9, 140.8, 157.9 and 159.2; νmax/cmϪ1 3201, 1713, 1611
and 1585; m/z 206 (M, 100%), 178 (21), 133 (39), 105 (47), 94
(11) and 78 (19). The second fraction (96 mg, 40%) was identi-
fied as unreacted starting material.
Photolysis of the isoxazolone 3 (100 mg) in acetone at 300
nm for 2 h gave the oxazole 4 (25 mg, 30%).
Ethyl 2-(2,5-dimethyloxazol-4-yl)-5-methyloxazole-4-
carboxylate 9
Ethyl 5-methyl-2-phenyloxazole-4-carboxylate 2 (R1 = Ph,
R2 = CO2Et, R3 = Me)
Photolysis (254 nm, acetonitrile, 30 min) of ethyl 2-benzoyl-4-
methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate (200 mg, 0.73
mmol) gave an oil which was chromatographed (dichloro-
methane–light petroleum, 7:3) to give one major fraction. A
second chromatogram (diethyl ether᎐light petroleum, 1:4),
gave the title compound as a colourless oil (67 mg, 40%) (lit.,35
Pyrolysis (500 ЊC, 140 ЊC, 5 × 10Ϫ5 mm) of a 4:1 mixture (270
mg) of N- and O-acylated derivatives from the reaction of ethyl
4-methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate with 2,5-
dimethyloxazole-4-carbonyl chloride and the usual work up
gave the title compound 9 (83 mg, 45%), mp 81–83 ЊC (Found:
Mϩ, 250.0935. C12H14N2O4 requires M, 250.0954); δH 1.40 (3 H,
t, J 7.12), 2.48 (3 H, s), 2.67 (3 H, s), 2.69 (3 H, s) and 4.39 (2 H,
q, J 7.12); δC 11.7, 12.1, 13.7, 14.3, 60.9, 124.4, 128.5, 150.2,
J. Chem. Soc., Perkin Trans. 1, 1997
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154.1, 155.5, 160.2 and 162.4; νmax/cmϪ1 1721, 1652 and 1618;
m/z 250 (M, 100%), 222 (5), 204 (48), 176 (55), 149 (3), 135 (9),
124 (97) and 97 (8).
J 1.25), 2.29 (3 H, s) and 7.13 (1 H, q, J 1.25); δC 10.9, 13.4,
133.7, 136.4 and 161.0.
Photolysis of the above mixture (145 mg) for 25 min in
acetonitrile at 300 nm gave the above oxazole (60 mg, 61%)
after radial chromatography (dichloromethane–light petrol-
eum, gradient). The isomeric ethyl 2-(2,5-dimethyloxazol-4-yl)-
4-methyloxazole-5-carboxylate (5 mg, 5%) was also obtained
(Found: Mϩ Ϫ C2H5O, 205.0637. C10H9N2O3 requires M,
205.0613); δH 1.32 (3 H, t, J 7.16), 2.41 (3 H, s), 2.43 (3 H, s),
2.58 (3 H, s) and 4.33 (2 H, q, J 7.16); δC 11.6, 13.7, 14.1, 22.3,
61.8, 124.9, 128.2, 131.1, 154.1, 158.6, 159.5 and 163.1; m/z 251
(M ϩ 1, 66%), 241 (5), 223 (3), 205 (61), 176 (3), 149 (1), 135
(3), 124 (100) and 96 (6).
2-Phenyloxazole39
Pyrolysis (590 ЊC, 100 ЊC, 0.05 mmHg, 30 min) of 2-benzoyl-
isoxazol-5(2H)-one (400 mg) gave the title compound as a
colourless oil (246 mg, 80%) (Found: Mϩ, 145.0523. Calc. for
C9H7NO: M, 145.0527); δH 7.26 (1 H, d, J 0.8), 7.46 (3 H, m),
7.71 (1 H, d, J 0.8) and 8.06 (2 H, m); δC 126.3, 127.3, 128.2,
128.8, 130.4, 138.6 and 162.0; m/z 145 (M, 100%), 122 (42), 117
(53), 105 (55), 90 (92), 77 (51) and 51 (46).
2-Methyl-4,5-diphenyloxazole40
Pyrolysis (540 ЊC, 155 ЊC, 0.05 mmHg, 60 min) of 2-acetyl-3,4-
diphenylisoxazol-5(2H)-one (300 mg) gave the title compound
(240 mg, 95%), bp 150 ЊC/1 mmHg, as a straw coloured oil
(Found: Mϩ, 235.1006. Calc. for C16H13NO: M, 235.0997); δH
2.51 (3 H, s), 7.27–7.37 (6 H, m) and 7.55–7.67 (4 H, m); δC
13.8, 126.3, 127.7, 127.9, 128.3, 128.4, 128.5, 130.4, 132.1,
135.1, 145.3 and 160.0; νmax/cmϪ1 1724, 1604 and 1594; m/z 235
(M, 67%), 207 (31), 206 (34), 165 (85), 105 (70), 77 (100), 51 (80)
and 43 (60).
Ethyl 2-[2-(2,5-dimethyloxazol-4-yl)-5-methyloxazol-4-yl]-5-
methyloxazole-4-carboxylate 10
Pyrolysis (590 ЊC; 100–200 ЊC gradient 15 ЊC per 15 min, 10Ϫ4
mm) of the product (120 mg) obtained from acylation of ethyl
4-methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate with the
acid chloride derived from hydrolysis of the above ester 9,
resulted in substantial decomposition. After 2 h only a small
amount (18 mg) of material had proceeded through the fur-
nace: the remainder had not sublimed. The residue in the sub-
limation flask was pre-adsorbed onto alumina and eluted with
diethyl ether to give a yellow solid, which was triturated with
cold diethyl ether and recrystallised from dichloromethane–
light petroleum to give the title compound as pale yellow needles
(10 mg, 9%), mp 162–165 ЊC (Found: Mϩ, 331.1142. C16H17-
N3O5 requires M, 331.1168); δH 1.41 (3 H, t, J 7.14), 2.49 (3 H,
s), 2.70 (3 H, s), 2.71 (3 H, s), 2.77 (3 H, s) and 4.40 (2 H, q, J
7.14); δC 11.7, 11.9, 12.2, 13.7, 14.4, 160.7, 128.6, 155.81, 154.1,
124.5, 150.1, 154.9, 125.6, 150.1 and 162.4; m/z 331 (M, 66%),
285 (7), 257 (45), 205 (14), 187 (4) and 123 (9). The volatile
material consisted of numerous unidentified products.
2,4,5-Triphenyloxazole
Pyrolysis (540 ЊC, 165 ЊC, 0.05 mmHg, 90 min) of 2-benzoyl-
3,4-diphenylisoxazol-5(2H)-one (280 mg) gave a solid (171 mg,
70%), mp 109–111 ЊC (lit.,41 mp 116 ЊC) which was identified by
comparison with an authentic sample (Found: Mϩ, 297.1158.
Calc. for C21H15NO: M, 297.1153); δH 7.35–7.57 (9 H, m), 7.77–
7.78 (4 H, m) and 8.20 (2 H, m); δC 126.5, 126.6, 127.4, 128.2,
128.2, 128.6, 128.6, 128.7, 128.8, 129.0, 130.4, 132.5, 136.7,
145.5 and 160.1; νmax/cmϪ1 769 and 694; m/z 297 (M, 100%), 269
(14) and 165 (55).
2-Trifluoromethyl-4-phenyloxazole
Pyrolysis (590 ЊC, 100 ЊC, 0.05 mmHg, 60 min) of 3-phenyl-2-
trifluoroacetylisoxazol-5(2H)-one (170 mg) appeared to
decompose the material and after 1 h no more material distilled
into the furnace. The oily title product (70 mg, 50%) was iso-
lated from the cold trap and solidified on standing, mp 46–
48 ЊC (Found: Mϩ, 213.0401. C10H6F3NO requires M,
213.0401); δH 7.39–7.78 (5 H, m) and 8.03 (1 H, s); δC 113.5 (q, J
177, CF3), 125.8, 129.0, 129.1, 132.2, 136.6, 142.0 and 150.8;
νmax/cmϪ1 1380 and 1245; m/z 213 (M, 100%), 185 (16), 103 (15),
90 (57) and 63 (26).
Ethyl 5-methyl-2-(phthalimidomethyl)oxazole-4-carboxylate 12
Photolysis (300 nm, acetonitrile, 2 h) of isoxazolone 13 (310
mg) gave a product which was eluted through a short plug of
silica (dichloromethane) and then recrystallised from ethanol–
water to give colourless needles (245 mg, 90%) of the title com-
pound, mp 166–167 ЊC (Found: Mϩ, 314.0888. C16H14N2O5
requires M, 314.0902); δH 1.33 (3 H, t, J 7), 2.54 (3 H, s), 4.32 (2
H, q, J 7), 4.95 (2 H, s), 7.74 (2 H, dd, J 5.5, 2.9) and 7.87 (2 H,
dd, J 5.5, 2.9); δC 12.02, 14.27, 34.51, 60.94, 123.67, 127.93,
131.94, 134.32, 156.10, 156.8, 161.9 and 167.1; νmax/cmϪ1 1716
and 1417; m/z 314 (M, 97%), 268 (14), 240 (17), 197 (79), 160
(100), 104 (24), 76 (24) and 43 (50).
Pyrolysis of 3-phenyl-2-(pyrrol-2-ylcarbonyl)isoxazol-5(2H)-one
1 (R1 = pyrrol-2-yl, R2 = Ph, R3 = H)
Pyrolysis of the reactant (200 mg) (540 ЊC, 150 ЊC, 0.05 mmHg,
1h) appeared to decompose the sample rapidly and only a small
amount of material (ca. 10–20 mg) sublimed into the furnace.
The product collected was N-phenylpyrrole-2-carboxamide (15
mg, 10%), mp 152–154 ЊC (lit.,42 153–154 ЊC); δH 6.48 (1 H, t, J
3.5), 7.21–7.41 (6 H, m) and 7.72 (1 H, dd, J 3.2, 1.6); νmax/cmϪ1
3118, 1698 and 1557; m/z 186 (M, 100%), 158 (11), 130 (22), 93
(46) and 64 (30).
Photolysis of 13 (160 mg) at 254 nm for 1 h afforded the title
compound (156 mg) in 80% yield.
2-Phenylbenzoxazole
Pyrolysis (595 ЊC, 150 ЊC, 0.05 mmHg, 90 min) of N-benzoyl-
benzisoxazolone (200 mg) gave a crude product which was
passed through a short plug of silica and recrystallised from
ethanol to give the title compound (147 mg, 90%) as white
needles, mp 103–105 ЊC (lit.,37 mp 102–104 ЊC) (Found: Mϩ,
195.0690. Calc. for C13H9NO: M, 195.0684); δH 7.31–7.35 (2 H,
m), 7.48–7.50 (3 H, m), 7.53–7.57 (1 H, m), 7.77–7.81 (1 H, m)
and 8.24–8.27 (2 H, m); δC 110.5, 119.9, 124.4, 125.0, 127.0,
127.5, 128.8, 131.4, 142.0, 150.6 and 162.9; νmax/cmϪ1 1618 and
1552; m/z 195 (M, 100%), 167 (13), 98 (5), 92 (7), 77 (10), 64 (18)
and 63 (21).
Ethyl 2-dichloromethyl-5-methyloxazole-4-carboxylate 2
(R1 = CHCl2, R2 = CO2Et, R3 = Me)
Pyrolysis (490 ЊC, 150 ЊC, 0.1 mmHg) of ethyl 2-dichloro-
methyl-4-methyl-5-oxo-2,5-dihydroisoxazole-3-carboxylate
(217 mg) gave a crude product which was subjected to radial
chromatography (diethyl ether–light petroleum, 1:3) affording
the title compound (33 mg, 18%) as a pale yellow oil (Found:
Mϩ, 236.9960; 238.9938. C8H9Cl2NO3 requires M, 236.9959;
238.9930); δH 1.40 (3 H, t, J 7.14), 2.71 (3 H, s), 4.40 (2 H, q,
J 7.14) and 6.71 (1 H, s); δC 12.2, 14.3, 59.9, 61.3, 127.9,
156.1, 158.3 and 161.4; νmax/cmϪ1 1722 and 1614; m/z 237 (M,
45%), 209 (16), 202 (100), 191 (66), 174 (46), 165 (24) and
156 (34).
2,4-Dimethyloxazole
Pyrolysis (595 ЊC, 100 ЊC, 0.05 mmHg, 15 min) of 2-acetyl-3-
methylisoxazol-5(2H)-one (150 mg) gave the title compound
(98 mg, 95%) as an oil, identical with the sample obtained in
very poor yield by the method of Oesterreich;38 δH 1.99 (3 H, d,
2670
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Diethyl 5-methyloxazole-2,4-dicarboxylate 19 (R = Et)
νmax/cmϪ1 1732, 1713, 1644 and 1606; m/z 199 (M, 23%), 171
(30), 154 (12), 143 (14), 125 (100) and 97 (9).
Pyrolysis (490 ЊC, 150 ЊC, 0.1 mmHg) of a 9:1 mixture (240 mg)
of the N- and O-acylated products from ethyl 4-methyl-5-oxo-
2,5-dihydroisoxazole-3-carboxylate and ethyl oxalyl chloride
gave a pale yellow oil which was subjected to silica radial chro-
matography (diethyl ether–light petroleum, 1:4) to give two
products. The first was the title compound (90 mg, 50% based
on N-acylated reactant) obtained as a white solid, mp 63–65 ЊC
(bp 120 ЊC/0.1 mmHg) (Found: C, 53.2; H, 6.0; N, 6.3%; Mϩ,
227.0798. C10H13NO5 requires C, 52.9; H, 5.8; N, 6.2%; M,
227.0794); δH 1.40 (3 H, t, J 7.14), 1.43 (3 H, t, J 7.14), 2.74 (3
H, s), 4.41 (2 H, q, J 7.14) and 4.48 (2 H, q, J 7.14); δC 12.3,
The second fraction was ethyl 2-ethoxy-4-methyloxazole-
5-carboxylate (13 mg, 7%). (Found: Mϩ, 199.0848. C9H13NO4
requires M, 199.0845); δH 1.33 (3 H, t, J 7.05), 1.39 (3 H, t,
J 6.98), 2.47 (3 H, s), 4.14 (2 H, q, J 7.05) and 4.25 (2 H, q,
J 6.98).
The material collected in the exit tube was passed through a
silica plug (methanol–ethyl acetate) affording ethyl 5-methyl-2-
oxo-2,3-dihydrooxazole-4-carboxylate 20 (76 mg, 49%) as a
white solid, identical with that characterised previously.
14.1, 14.3, 61.3, 62.9, 129.5, 150.1, 155.3, 159.1 and 161.3; νmax
/
Ethyl 5-methyl-2-phenoxyoxazole-4-carboxylate 22 (R = Ph)
Isoxazolone (115 mg) 21 (R = Ph) was subjected to flash
vacuum pyrolysis (490 ЊC, 150–200 ЊC, 0.1 mmHg). The crude
material, collected from both the exit tube and the cold trap,
was subjected to radial chromatography (diethyl ether–light
petroleum, 2:3) affording the title compound (62 mg, 64%) as a
colourless oil (Found: Mϩ, 247.0842. C13H13NO4 requires M,
247.0845); δH 1.36 (3 H, t, J 7.13), 2.58 (3 H, s), 4.34 (2 H, q, J
7.13), 7.19–7.26 (1 H, m) and 7.31–7.43 (4 H, m); δC 11.7, 14.1,
60.8, 119.2, 125.7, 126.6, 129.8, 151.9, 153.2, 157.5 and 162.2;
νmax/cmϪ1 1732, 1634, 1581 and 1493; m/z 247 (M, 31%), 201
(10), 126 (8), 104 (12) and 94 (100).
cmϪ1 1734, 1718, 1595 and 1550; m/z 227 (M, 44%), 199 (14),
182 (25), 171 (20), 155 (21), 143 21), 127 (16) and 109 (33).
The second fraction was an oil, identified by its spectral
properties as diethyl 4-methyloxazole-2,5-dicarboxylate (7 mg,
4%); δH 1.436 (3 H, t, J 7.14), 1.440 (3 H, t, J 7.14), 2.51 (3 H, s),
4.46 (2 H, q, J 7.14) and 4.47 (2 H, q, J 7.14); νmax/cmϪ1 1738,
1732 and 1615; m/z 227 (M, 3%), 182 (30), 171 (14), 154 (20),
143 (10), 125 (31), 110 (25) and 99 (23).
Ethyl 2-methoxycarbonyl-5-methyloxazole-4-carboxylate 19
(R = Me)
Pyrolysis (490 ЊC, 150 ЊC, 0.01 mmHg) of a 9:1 mixture (309
mg) of N- and O-acyl derivatives from ethyl 4-methyl-5-oxo-
2,5-dihydroisoxazole-3-carboxylate and methyl oxalyl chloride
gave an oil which was subjected to silica radial chromatography
(dichloromethane–light petroleum, gradient) to give two frac-
tions. The first was the title compound (106 mg, 46% based on
N-acylated reactant) obtained as a transparent solid after distil-
lation, mp 92–94 ЊC (bp 140–150 ЊC/0.2 mmHg) (Found: C,
50.7; H, 5.1; N, 6.2. C9H11NO5 requires C, 50.7; H, 5.2; N,
6.6%); δH 1.41 (3 H, t, J 7.14), 2.75 (3 H, s), 4.01 (3 H, s) and
4.42 (2 H, q, J 7.14); δC 12.2, 14.1, 53.1, 61.2, 129.4, 149.6,
155.5, 159.1 and 161.1; νmax/cmϪ1 1745, 1707 and 1598; m/z 213
(M, 21%), 185 (7), 167 (34), 141 (11) and 129 (4).
The second fraction was characterised as ethyl 5-methyl-2-
oxo-2,3-dihydrooxazole-4-carboxylate 20 (6 mg, 3% based on
N-acylated reactant) obtained as a white solid, mp 116–120 ЊC
after recrystallisation from dichloromethane–light petroleum
(Found: Mϩ, 171.0532. C7H9NO4 requires M, 171.0532); δH
1.36 (3 H, t, J 7.13), 2.40 (3 H, s), 4.34 (2 H, q, J 7.13) and 8.4
(1 H, br s); δC 12.0, 14.3, 61.6, 114.2, 146.6, 153.1 and 158.9;
m/z 171 (M, 22%), 143 (24), 125 (45), 113 (3), 83 (18) and
69 (100).
Ethyl 2-(2,5-diphenyloxazol-4-yl)-5-methyloxazole-4-carboxy-
late 23
Pyrolysis (490 ЊC, 280 ЊC, 0.1 mmHg) of a 76:24 mixture (185
mg) of the N- and O-acylated products derived from the reac-
tion of ethyl 4-methyl-5-oxo-2,5-dihydroisoxazole-3-carboxyl-
ate with 2,5-diphenyloxazole-4-carbonyl chloride and the usual
work up gave the title compound (40 mg, 32%), mp 136–139 ЊC
(Found: C, 70.7; H, 4.8; N, 7.4%; Mϩ, 374.1262. C22H18N2O4
requires C, 70.6; H, 4.9; N, 7.5%; M, 374.1267); δH 1.43 (3 H, t,
J 7.14), 2.75 (3 H, s), 4.41 (2 H, q, J 7.14), 7.4–7.6 (6 H, m), 8.1–
8.2 (2 H, m) and 8.3–8.4 (2 H, m); δC 12.2, 14.3, 60.9, 124.9,
126.4, 126.8, 127.1, 127.4, 128.6, 128.7, 128.8, 129.8, 131.0,
150.4, 153.8, 156.4, 160.3 and 162.2; νmax 1772, 1712, 1652 and
1627; m/z 374 (M, 4%), 221 (9), 178 (20), 167 (14), 149 (24), 131
(5), 122 (37) and 105 (100).
Photolysis of the above mixture (135 mg) for 25 min in ben-
zene at 300 nm gave the oxazole (24 mg) in 26% yield after
radial chromatography (dichloromethane–light petroleum,
gradient): the isomeric oxazole was obtained in trace amounts.
4,4Ј-Bis(ethoxycarbonyl)-5,5Ј-dimethyl-2,2Ј-bi(oxazole) 24
Pyrolysis (540 ЊC, 250 ЊC, 0.01 mmHg) of N,NЈ-bis(3-ethoxy-
carbonyl-4-methyl-5-oxo-2,5-dihydoisoxazol-2-yl)oxamide (230
mg) resulted in the material decomposing: only a small amount
of solid material was collected in the exit tube. This material
was passed through a silica plug (diethyl ether) and the residue
triturated with cold diethyl ether to give the title compound as a
white solid (16 mg, 8%), mp 208–209 ЊC (Found: Mϩ, 308.0998.
C14H16N2O6 requires M, 308.1008); δH 1.41 (6 H, t, J 7.14), 2.74
(6 H, s) and 4.43 (4 H, q, J 7.14); δC 12.3, 14.4, 61.4, 129.4,
148.3, 158.3 and 161.5; νmax/cmϪ1 1717, 1607 and 1501; m/z 308
(M, 60%), 262 (46), 235 (26), 183 (62), 164 (9) and 155 (34).
Ethyl 2-methoxy-5-methyloxazole-4-carboxylate 22 (R = Me)
Isoxazolone 21 (R = Me) (190 mg) was subjected to flash vac-
uum pyrolysis (490 ЊC, 150 ЊC, 0.1 mmHg). The crude product,
collected in both the exit tube and the cold trap, was subjected
to radial chromatography (diethyl ether–light petroleum, 1:3)
affording the title compound (101 mg, 66%) as a colourless oil
(Found: Mϩ, 185.0688. C8H11NO4 requires M, 185.0688); δH
1.38 (3 H, t, J 7.13), 2.53 (3 H, s), 4.11 (3 H, s) and 4.38 (2 H, q,
J 7.13); δC 11.7, 14.2, 59.3, 60.8, 126.4, 151.4, 160.4 and 162.4;
νmax/cmϪ1 1732, 1651 and 1615; m/z 185 (M, 33%), 157 (9), 139
(61), 125 (26), 111 (13) and 84 (6).
A trace of ethyl 2-methoxy-4-methyloxazole-5-carboxylate
(<1%) was also obtained.
2,6-Bis(4-ethoxycarbonyl-5-methyloxazol-2-yl)pyridine 25
Injection flash vacuum pyrolysis (thin bore needle) (490 ЊC, 0.01
mmHg) of a 8:1:1 mixture of bis-N-, bis-O- and N,O-acylated
compounds (111 mg) from ethyl 4-methyl-5-oxo-2,5-dihydro-
isoxazole-3-carboxylate and pyridine-2,6-dicarbonyl chloride,
dissolved in chlorobenzene (0.5 ml) gave a product (79 mg)
which decomposed substantially on chromatography. Use of a
short plug of silica treated with triethylamine allowed the isol-
ation of pale yellow crystals, mp 197–199 ЊC (dichloromethane–
light petroleum), but an analytically pure sample could not be
obtained, δH 1.44 (6 H, t, J 7.14), 2.80 (6 H, s), 4.45 (4 H, q, J
7.14), 7.98 (1 H, dd, J 8.6, 7.65) and 8.34 (2 H, d, J 8.6); δC 12.5,
Ethyl 2-ethoxy-5-methyloxazole-4-carboxylate 22 (R = Et)
Isoxazolone 21 (R = Et) (220 mg) was subjected to flash vac-
uum pyrolysis (490 ЊC, 150 ЊC, 0.1 mmHg). Material collected
in the cold trap was subjected to radial chromatography (diethyl
ether–light petroleum, 2:3) affording the title compound (56
mg, 31%) as a colourless oil (Found: Mϩ, 199.0847. C9H13NO4
requires M, 199.0845); δH 1.37 (3 H, t, J 7.2), 1.42 (3 H, t, J
6.98), 2.52 (3 H, s), 4.37 (2 H, q, J 7.2) and 4.50 (2 H, q, J 6.98);
δC 11.7, 14.2, 14.3, 60.8, 67.8, 126.4, 151.1, 152.6 and 162.6;
J. Chem. Soc., Perkin Trans. 1, 1997
2671

View Online
14 R. D. Connell, M. Tebbe, P. Helquist and B. Akermark, Tetrahedron
14.4, 61.3, 123.7, 129.4, 138.2, 145.6, 158.0 and 162.1; νmax/cmϪ1
1715, 1609, 1592 and 1551; m/z 385 (M, 100%), 341 (4), 259
(13), 232 (94), 204 (12), 186 (28) and 149 (10).
Lett., 1991, 32, 17.
15 K. J. Doyle and C. J. Moody, Tetrahedron, 1994, 50, 3761.
16 R. H. Prager and Y. Singh, Aust. J. Chem., 1992, 45, 1811.
17 R. H. Prager and Y. Singh, Tetrahedron, 1993, 49, 8147.
18 R. H. Prager, Y. Singh and B. Weber, Aust. J. Chem., 1994, 47,
1249.
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We thank the Australian Research Committee for financial
support. J. A. S. and C. M. W. acknowledge Australian
Postgraduate Awards.
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Paper 7/00134G
Received 6th January 1997
Accepted 30th April 1997
2672
J. Chem. Soc., Perkin Trans. 1, 1997