Ortho substituent effects on transfer of aryl groups from oxygen to carbon in adducts from diaryloxycarbenes and DMAD

Article abstract of DOI:10.1139/v02-012

Diaryloxycarbenes, generated by thermolysis of 2,2-diaryloxy-5,5-dimethyl-Δ³-1,3,4-oxadiazolines in benzene, reacted with dimethyl acetylenedicarboxylate (DMAD) to afford triesters. The triesters arose by aryl-group transfer from oxygen to carb

Full text of DOI:10.1139/v02-012

228
Ortho substituent effects on transfer of aryl
groups from oxygen to carbon in adducts from
diaryloxycarbenes and DMAD
Xiaosong Lu and John Warkentin
Abstract: Diaryloxycarbenes, generated by thermolysis of 2,2-diaryloxy-5,5-dimethyl-∆3-1,3,4-oxadiazolines in benzene,
reacted with dimethyl acetylenedicarboxylate (DMAD) to afford triesters. The triesters arose by aryl-group transfer
from oxygen to carbon (ipso substitution). A cyano group in the para position had been shown earlier to favour the
ipso substitution whereas a para-methoxy group disfavoured it. Surprisingly, the ortho-methoxy substituent also fa-
voured ipso substitution. As a tentative rationale, we had proposed that a vinylogous diaryloxycarbene intermediate,
with dipolar properties, is formed when a diaryloxycarbene attacks at the sp-carbon of DMAD and that an ortho
substituent, with one or more unshared electron pairs, can stabilize the intermediate by donating electron density to the
positive site. In the present work, support for that interpretation and for the importance of a steric effect, was provided
by examining the competition between (i) p-tolyl and phenyl; (ii) o-tolyl and phenyl; (iii) o-iodophenyl and phenyl;
(iv) o-iodophenyl and p-chlorophenyl; and (v) o-bromophenyl and p-chlorophenyl as potential migrating groups.
Key words: aromatic substitution, carbene, ipso, diaryloxycarbene, oxadiazoline.
Résumé : Les diaryloxycarbènes, générés par thermolyse de 2,2-diaryloxy-5,5-diméthyl-∆3-1,3,4-oxadiazolines dans le
benzène, réagissent avec l’acétylènedicarboxylate de diméthyle («DMAD») pour conduire à la formation de triesters.
Les triesters se forment par un transfert de groupe acyle de l’oxygène au carbone (substitution ipso). Il a été démontré
antérieurement que la présence d’un groupe cyano en position para favorise la substitution ipso alors qu’un groupe mé-
thoxy la défavorise. De façon surprenante, un substituant méthoxy en ortho favorise aussi la substitution ipso. Comme
explication de ce résultat, on a suggéré que lorsqu’un diaryloxycarbène attaque au niveau d’un carbone sp du DMAD,
il y formation d’un intermédiaire diaryloxycarbène vinylogue ayant des propriétés dipolaires et qu’un substituant ortho
possédant au moins une paire d’électrons non partagée peut stabiliser l’intermédiaire en donnant de la densité électro-
nique au site positif. Dans le présent travail, en examinant la compétition entre divers groupes migrants potentiels
((i) p-tolyle et phényle; (ii) o-tolyle et phényle; (iii) o-iodophényle et phényle; (iv) o-iodophényle et p-chlorophényle;
(v) o-bromophényle et p-chlorophényle), on a obtenu des résultats qui appuient cette interprétation et qui mettent en
évidence l’importance d’un effet stérique.
Mots clés : substitution aromatique, carbène, ipso, diaryloxycarbène, oxadiazoline.
[Traduit par la Rédaction] Lu and Warkentin 234
Introduction
volve the acyclic dipole. The dipolar species may be in
equilibrium with the cyclopropenes, many of which are not
stable enough at higher temperatures to accumulate to de-
tectable concentrations (2).
We became interested in reactions of methoxyaryloxy-
and diaryloxycarbenes with DMAD as a result of the discov-
ery of aryl group transfer, from oxygen to carbon, to pro-
duce triester products (Scheme 2) (3, 4).
There was only one prior example of a similar transfer,
from the reaction of an aminothiocarbene with DMAD,
Scheme 3 (5). The results in Schemes 2 and 3 could be ra-
tionalized in terms of a dipolar carbenic intermediate that
accomplishes ipso-aromatic substitution, either by nucleo-
philic attack at the ipso carbon or via cyclopropanation and
subsequent reorganization (Scheme 4) as suggested by
Capretta (6) for similar reactions of carbenoids. The mecha-
nism involving nucleophilic attack was favoured when it was
found that an electron withdrawing group in the para position
favoured aryl-group transfer whereas an electron donor group
disfavoured the transfer (4). For example, p-cyanophenyl mi-
Reactions of neutral nucleophiles with Michael acceptors
will generally involve dipolar intermediates, as illustrated in
Scheme 1 for the attack of an amine on dimethyl acetylene-
dicarboxylate (DMAD). If the nucleophile is a carbene, such
as a dialkoxycarbene, the attack can produce either a dipole
or a cyclopropene, depending on whether the reaction is
stepwise or concerted. It is not always easy to distinguish
between the stepwise addition with subsequent ring-closing
and the concerted cyclopropene formation with subsequent
ring-opening, but it is fairly clear that, with a few excep-
tions (1), reactions subsequent to the initial attack often in-
Received 16 September 2001. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 6 March 2002.
X. Lu and J. Warkentin.1 Department of Chemistry,
McMaster University, Hamilton, ON L8S 4M1, Canada.
1Corresponding author (e-mail: warkent@mcmaster.ca).
Can. J. Chem. 80: 228–234 (2002)
DOI: 10.1139/V02-012
© 2002 NRC Canada

Lu and Warkentin
229
Scheme 1.
Scheme 3.
NO2
+
NO2
N
O2N
EC CE
R3N
_
R3N +
MeO2C
CO2Me
E
E
CO2Me
_
MeO2C
60-80 0C
PhH
RO OR
+
N
(RO)2C
H
N
S
N
MeO C
CO2Me
N
:
(RO)2C: +
N
2
S
OR
CO2Me
MeO2C
S
MeO2C
CO2Me
Ar
Ar
Ar
(RO)2C
MeO2C
(R=H, Me; E= CO2Et)
..
CO2Me
Scheme 4.
Scheme 2.
PhO
E
O
E
PhO
E
O
X
X
RO
N
OAr
O
RO2C
Ar
E
heat
DMAD
E
E
E
N
PhO
E
OC6H4X PhO
OC6H4X
+
(R= Me or aryl; DMAD= dimethyl
acetylenedicarboxylate; E= CO2Me)
OPh
_
:
E
OC6H4X
E
E
E
grated exclusively when competing with phenyl, p-tolyl, or
p-methoxyphenyl, and phenyl migrated exclusively when in
competition with p-methoxyphenyl (4). Surprisingly, o-meth-
oxyphenyl had a migratory aptitude comparable to that of
phenyl (4), suggesting that the o-methoxy substituent exerts
opposing effects, an electronic effect presumably analogous
to that of the p-methoxy substituent, disfavouring substitu-
tion, and at least one other effect favouring it.
We now report that the o-tolyl group has a higher migra-
tory aptitude than the p-tolyl group, although both have a
lower migratory aptitude than the phenyl group, and that the
ortho effect is enhanced with the o-iodo- and o-bromophenyl
groups, both of which migrated in preference to the p-chlor-
ophenyl group.
PhO
E
O
E
X
PhO
E
O
_
+
X
E
form triesters 10 and 11 through migration of an aryl group
from oxygen to carbon. In the case of 8a (Ar = p-C6H4Me),
10a was the minor and 11a the major triester formed
(10a:11a = 1:4.5). Similarly, in the case of 8b, the yield of
11b exceeded that of 10b (11b:10b = 1.1:1). Thus, the para-
methyl group retards migration between 4- and 5-fold,
whereas the ortho-methyl group retards migration by about
10%, both relative to H. However, o-iodophenoxy-
(phenoxy)carbene (not shown) reacted with DMAD to afford
exclusively the triester from migration of the o-iodophenyl
group. Similarly, the o-iodophenyl and the o-bromophenyl
groups migrated exclusively when in competition with the p-
chlorophenyl group of 8c and 8d. These results are in Ta-
ble 1, together with some results published earlier.
Identification of the triester formed by ipso-aromatic sub-
stitution by means of mass spectrometry was straightfor-
ward. For example, esters 10a and 10b gave rise to a base
peak from loss of the C6H5O fragment of the ester; the aryl
group that had migrated to carbon was not lost. On the other
hand, 11b lost the fragment CH3C6H4O. Esters 10 and 11
were assigned the E-configuration on the basis of analogy to
a similar compound, the structure of which was secured by
means of X-ray diffraction (4).
In each case, the oxadiazoline source fragmented not only
to N2, the carbene, and acetone, but also to 2-diazopropane
and the appropriate diaryl carbonate (Scheme 6). The diazo-
propane was trapped by 1,3-dipolar cycloaddition to DMAD
to form known pyrazole 12 (11).
These results can be interpreted as follows: attack on
DMAD by the carbenes 8 leads to isomeric dipolar interme-
diates (9), which can also be represented as vinylogous
dioxycarbenes (not shown) that are equilibrated by revers-
ible closure to the appropriate cyclopropene. Such equilibra-
tion occurs at 80°C in the case of analogous vinylogous
dioxycarbenes (2c). If equilibration via the corresponding
Methods, results, and discussion
Oxadiazolines 4 were prepared from appropriate bis(aryl)
carbonates (1). Diphenyl carbonate is commercially avail-
able and di(p-chlorophenyl) carbonate was prepared from
1,1′-carbonyl diimidazole by the sequence of reactions
shown in Scheme 5 (7).
Diaryloxyoxadiazolines 5 were prepared by exchange re-
actions of oxadiazolines 4 with the appropriate substituted
phenols (7, 8). Thermolysis of 5 in benzene generated car-
bonates 6 and carbonyl ylides 7 by competing 1,3-dipolar
cycloreversions (see Scheme 6). Evidence for the inter-
mediacy of 7 came from the thermolysis-rate constants (7).
Although the effects of the substituents on the thermolysis-
rate constants are small, the fact that the p-cyano substituted
oxadiazoline lost N2 about twice as fast as the parent is con-
sistent with a transition state in which C2 has become more
negative, as it would in the carbonyl ylide. In a concerted
mechanism, on the other hand, in which N2 and acetone are
extruded simultaneously, as proposed by Smith (9), carbene
character would develop at C2. A cyano group, which would
destabilize the carbene, should have a rate-retarding effect
and not the observed rate-accelerating effect, if carbene for-
mation were part of the rate-determining step.
Diaryloxycarbenes 8, which presumably arose from frag-
mentation of carbonyl ylides 7 (10), reacted with DMAD to
© 2002 NRC Canada

230
Can. J. Chem. Vol. 80, 2002
Scheme 5.
Scheme 6.
O
XC6H4O OAr
OAr
XC6H4O
XC6H4OH
-N2
-Me2CO
XC6H4O
N
OAr
N
N
O
_
(XC6H4O)2CO
XC6H4O OAr
+
O
..
-Me2CN2
N
N
N
1a, X=H; 1b, X=p-Cl
O
6
5
7
8
.
1 + H2NNH2 H2O
XC6H4O(CO)NHNH2
2a, X=H; 2b, X=p-Cl
ArO
O
E
XC6H4O
E
O
ArO
OC6H4X
_
XC6H4O
+
OAr
_
+
2 + Me2CO
XC6H4OCONHN=CMe2
3a, X=H; 3b, X=Cl
E
E
+
+
C6H4X
8
Ar
E
E
E
E
10
E
E
9
11
XC6H4O OAr
XC6H4O OAc
ArOH
LTA
CH2Cl2
N
O
N
O
E
3
+
H
OC6H4X
OAr
N
N
4
5
E
a: X=H, Ar= p-MeC6H4; b: X=H, Ar= o-MeC6H4;
c: X=p-Cl, Ar= o-IC6H4; d: X=p-Cl, Ar= o-BrC6H4;
e: X= H, Ar= o-IC6H4
(a: X= H, Ar= p-MeC6H4; b: X= H, Ar= o-MeC6H4; c: X= p-Cl, Ar= o-IC6H4; d: X= p-Cl,
Ar= o
e: X= H, Ar= o-IC H ; E=CO Me)
;
2
6
4
Me
Me
Me2CN2 + DMAD
E
N
Table 1. Yields and yield ratios of ipso substitution products 10,
11 in Scheme 6.
N
E
12
Major migrating
group (%)
Minor migrating
group (%)
Ratioa
Scheme 7.
C6H5 (34)
C6H5 (25)
C6H5 (38)
o-MeOC6H4 (25)
p-NCC6H4 (37)
p-NCC6H4 (26)
p-NCC6H4 (37)
o-IC6H4 (45)
o-IC6H4 (38)
o-BrC6H4 (38)
p-C6H4Me (8)
o-C6H4Me (22)
p-MeOC6H4 (nd)b
C6H5 (11)
p-MeOC6H4 (nd)
p-MeC6H4 (nd)
C6H5 (nd)
C6H5 (nd)
p-ClC6H4 (nd)
p-ClC6H4 (nd)
4.5
1.1
Largec
2.3c
Largec
Largec
Largec
Large
Large
Large
O
+
O
+
_
XC6H4O
XC6H4O
O
XC6H4O
+
Y
Y
Y
_
_
E
E
E
E
E
E
(coplanar, or nearly so)
(Y= Me, MeO, I, Br)
(rotated out of plane)
(Y= OMe, I, Br)
a strong facilitator of migration whereas a para-methoxy
group stops aryl migration, both relative to H. Although it
was not possible to construct a Hammett plot and to deter-
mine the value of ρ, an approximate value can be estimated
as follows: if we assume that no more than 2% of a minor
product might have been missed, then the migration rate ratios
were p-CNC6H4/C6H5 > 37/2 and p-MeOC6H4/C6H5 < 2/38
(4). Consequently kp-CN/kH ≥ 18.5 or log (kp-CN/kH) ≥ 1.27 and
kp-OMe/kH ≤ 1/19 or log (kp-OMe/kH) ≤ –1.28. With σp-Cl = 0.63
and σp-OMe = –0.27, the predicted value of ρ is ca. +3.3. The
value of σp-Cl is 0.23, which, together with the estimated
value of ρ, leads to the prediction that the p-chlorophenyl
group should migrate 5 to 6 times faster than phenyl. Since
o-iodophenyl and o-bromophenyl migrated exclusively when
in competition with p-chlorophenyl, it is clear that both the
ortho-iodo and ortho-bromo substituents enhance migration,
relative to H, even more strongly. The large rate-enhancing
effects of o-iodo and o-bromo, relative to H and to p-chloro,
cannot be a consequence of relative electron withdrawing
abilities, which are very similar (σp-I = 0.28, σp-Br = 0.23,
σp-Cl = 0.23).
A likely explanation for the observed effects (o-MeO >>
H, p-MeO < H; o-I > p-Cl > H; o-Br > p-Cl > H; o-Me < H,
p-Me < H; and o-Me > p-Me) focuses on the following fac-
tors: (i) in a nucleophilic ipso substitution, electron donor
groups should raise the transition state energy; (ii) p-methoxy
and p-methyl groups are donor groups relative to H and both
retard the ipso substitution; (iii) methyl retards moderately
and methoxy retards more strongly, as expected on the basis
of their substituent constants (σp-Me = –0.14, σp-OMe = –0.28);
aFrom the actual yields and not the rounded figures in the first two
columns.
bNot detected.
cReference 4.
cyclopropenes is rapid compared to aryl group transfer, then
the Curtin–Hammett principle (12) applies and the group
that is transferred by ipso substitution is selected on the ba-
sis of the relative stabilities of the transition states and not
the ground states. Given that the principle does apply, it is
clear from Table 1 that the p-tolyl group is transferred more
slowly than the phenyl group, whereas the o-tolyl group, al-
though it is also transferred more slowly than the phenyl
group, is transferred more rapidly than the p-tolyl group.
Thus, methyl retards nucleophilic aromatic substitution, as
befits its electronic effect, but the retardation is diminished
when the methyl group is situated ortho. Presumably the o-
methyl group acts to prevent coplanarity of the aryloxy
group with the dipolar fragment tethered to it (see
Scheme 7) and that geometry provides an improved orienta-
tion of the aryloxy group for attack on the ring. Whether that
attack involves formation of one bond, at the ipso position
only, or two bonds to the aromatic ring to afford a cyclo-
propane intermediate (6) is not established.
Both o-iodophenyl and o-bromophenyl are transferred
more rapidly than p-chlorophenyl, to the extent that the
products of migration of p-chlorophenyl were not found.
From previous work (4), we know that the p-cyano group is
© 2002 NRC Canada

Lu and Warkentin
231
and (iv) p-cyano and p-chloro are inductively electron with-
drawing and cyano also withdraws conjugatively. One there-
fore expects them to favour ipso substitution on rings
bearing those groups, as observed for p-cyano. Ortho
groups, on the other hand, must exert three effects. First,
they donate or withdraw electrons, qualitatively like their
para counterparts. Second, they exert a steric effect that fa-
vours attack at the neighbouring carbon (ipso attack), as in-
dicated by the effect of o-methyl. The fact that p-methyl is
retarding and o-methyl is retarding but less so must mean
that the steric effect promotes attack by the dipole–carbene
on the aromatic ring. Presumably it does this by increasing
the populations of conformers in which the aromatic ring to
be attacked is not coplanar with the dipolar–carbenic
nucleophile (Scheme 7). Third, the ortho substituents bear-
ing unshared electrons (MeO, I, Br) must exert a further ef-
fect that reinforces the steric effect; these substituents can
donate electron density toward the developing positive site
to stabilize the transition state for the formation of the inter-
mediate for nucleophilic-aromatic ipso substitution, illus-
trated in Scheme 7. A cyclopropanation step would also be
facilitated by rotating the aromatic ring as a result of steric
hindrance. However, cyclopropanation by a nucleophilic
carbene is unlikely to be enhanced strongly by an o-OMe
substituent.
General thermolysis method
All thermolyses were carried out by immersing the sealed
and vacuum-degassed thermolysis tubes containing the sam-
ples in a constant-temperature oil bath at 110.0 ± 0.2°C for
24 h. In a typical procedure a solution containing the oxa-
diazoline (0.6 mmol) and DMAD (0.8 mmol) in benzene
(20 mL) was degassed by means of three freeze-pump-thaw
cycles before it was heated in a sealed tube at 110°C for
24 h. A small amount of the solution was used for direct
GC–MS analysis. Benzene was evaporated from the rest of
the solution and the residue was subjected to flash chroma-
tography with 5% ethyl acetate in hexane as the eluting sol-
vent. The spectroscopic data came from products isolated by
means of radial or column chromatography from larger-scale
experiments with up to 2.2 mmol of oxadiazoline.
bis-p-Chlorophenyl carbonate (1b) (14)
A solution of 1,1′-carbonyldiimidazole (9.7 g, 0.060 mol),
p-chlorophenol (15.2 g, 0.12 mol), silver nitrate (20.4 g,
0.12 mol), and triethylamine (12.1 g, 0.12 mol) in aceto-
nitrile (100 mL) was heated at reflux for 16 h before it was
filtered and cooled to room temperature. Hexane was added
until no more precipitate was formed. The colourless nee-
dle-shaped crystals (9.6 g, 57%) were removed from the
slightly dark solution by vacuum filtration; mp 146–147°C.
IR (CCl4) (cm–1): 1781 (s), 1488 (s), 1278 (m), 1224 (br),
Thus, the tentative explanation advanced earlier (4), for
the electronic effect of the o-methoxy substituent, is sup-
ported by the findings that the o-Br and o-I substituents are
strongly rate enhancing. That explanation is amplified, on
the basis of the results with o- and p-Me, to include a pure
steric effect.
1
1187 (s), 1163 (m), 1104 (m), 1085 (s), 1013 (s). H NMR
(200 MHz, CDCl3) δ: 7.19–7.40. 13C NMR (75 MHz,
CDCl3) δ: 122.3, 129.8, 132.0, 149.4, 151.7. EI-MS m/z (%):
286 (M+, 10), 284 (M+, 54), 282 (M+, 90), 238 (52), 168
(25), 128 (42), 111 (100), 99 (59), 75 (68), 63 (46). CI-MS
(NH3) m/z (%): 304 ([M + 18]+, 1), 302 ([M + 18]+, 7), 300
([M + 18]+, 10), 282 (M+, 27).
p-Chlorophenyl hydrazinecarboxylate (2b) (14)
Experimental
A stirred solution of bis-p-chlorophenyl carbonate (4.0 g,
0.014 mol) in CH2Cl2 (30 mL) was cooled with a dry ice
bath for 15 min before hydrazine monohydrate (0.71 g,
0.014 mol) was added in one portion. The dry ice was re-
moved to let the solution warm gradually to room tempera-
ture and stirring was continued for 20 min. Addition of
hexane caused colourless needles to precipitate. Vacuum fil-
tration furnished pure 2b (1.06 g, 40%); mp 144–145°C. IR
(CCl4) (cm–1): 3458 (m), 3304 (m), 1757 (s), 1549 (s), 1462
(m), 1215 (s), 1010 (m), 978 (m). 1H NMR (200 MHz,
CDCl3) δ: 3.87 (s, 2H, NH2), 6.35 (s, 1H, NH), 7.07–7.31
(m, 4H, Ar). 13C NMR (50 MHz, CDCl3) δ: 122.9, 129.6,
131.2, 149.3, 156.7.
NMR spectra were recorded on a Bruker AC-200 or AC-
300 NMR spectrometer. Infrared spectra were recorded with
a Biorad FTS-40 spectrophotometer, with the sample either
in CCl4 or in a KBr pellet. The IR bands are labeled qualita-
tively with the symbols br, s, and m for broad, strong, and
medium intensities, respectively. Bands from C—H stretch-
ing vibrations between 3100 and 2850 cm–1 are omitted, as
are other weak bands. Melting points were recorded on a
Thomas Hoover capillary melting point apparatus; they are
uncorrected. Mass spectra of compounds containing Cl, Br,
or both list all of the observed molecular ion masses, not
only the signals for the most abundant isotope(s). Mass
spectra for the oxadiazolines are not reported. 2,2-Dioxy-
5,5-dimethyl oxadiazolines do not, in general, afford molec-
ular ion signals and their mass spectra have little diagnostic
p-Chlorophenoxycarbonyl hydrazone of acetone (3b)
p-Chlorophenyl hydrazinecarboxylate (3.73 g, 0.020 mol)
and anhydrous magnesium sulfate (ca. 6 g) were added to
acetone (60 mL). Stirring for 24 h followed by filtration and
evaporation of the excess acetone produced pure 3b as
colourless crystals (92% yield); mp 98–102°C. IR (CH2Cl2)
(cm–1): 3383 (m), 1761 (s), 1482 (m), 1356 (m), 1262 (s),
1
value. They can be recognized from their H and 13C NMR
spectra. The latter typically show C2 between δ 136 and 138
and C5 between δ 118 and 120, if the C2 substituents are
alkoxy groups and the C5 substituents are methyl groups
(13). Some of the 13C NMR spectra of the products showed
fewer signals than were expected and coincidence of some
signals in diaryl compounds is suspected. Moreover, some
maleate-like methyl esters (10, 11) gave only one 13C OMe
signal where two methoxy groups were indicated by 1H
NMR spectroscopy.
1
1201 (m), 1090 (m), 1012 (m). H NMR (200 MHz, CDCl3)
δ: 1.88 (s, 3H, CH3), 2.08 (s, 3H, CH3), 7.10–7.36 (m, 4H,
Ar), 7.97 (s, 1H, NH). 13C NMR (75 MHz, CDCl3) δ: 16.4,
25.5, 123.0, 129.5, 131.1, 149.3, 153.1. EI-MS m/z (%): 229
([M + 1]+, 5), 227 ([M + 1]+, 15), 128 (74), 99 (100), 56
© 2002 NRC Canada

232
Can. J. Chem. Vol. 80, 2002
(37). CI-MS (NH3) m/z (%): 229 ([M + 1]+, 32), 227 ([M +
1]+, 100). EI-HRMS m/z calcd. for C10H1135ClN2O2:
227.0587; found: 227.0575.
CDCl3) δ: 53.3, 96.4, 122.2, 128.1, 129.3, 129.4, 130.4,
131.7, 132.9, 139.0, 139.1, 146.6, 148.2, 160.9, 163.8,
164.8. EI-MS m/z (%): 373 ([M – OC6H4Cl]+, 100), 255
(38), 246 (53), 215 (57), 187 (48), 173 (39), 128 (100), 115
(53), 99 (67), 64 (67), 59 (86). CI-MS (NH3) m/z (%): 520
([M + 18]+, 35), 518 ([M + 18]+, 100), 503 ([M + 1]+, 14),
501 ([M + 1]+, 43).
2-Acetoxy-2-(p-chlorophenoxy)-5,5-dimethyl-∆3-1,3,4-
oxadiazoline (4c)
A solution of lead tetraacetate (LTA, 11.4 g, 2.57 mmol)
in CH2Cl2 (60 mL) was cooled with dry ice in isopropyl al-
cohol. Acetone p-chlorophenoxycarbonyl hydrazone (4.84 g,
2.14 mmol) in CH2Cl2 (20 mL) was added dropwise to the
LTA solution, which was then gradually warmed to room
temperature and stirred overnight. After three washings with
5% NaHCO3, drying over anhydrous MgSO4, and evapora-
tion of the solvent, flash column chromatography (5%
EtOH–hex) gave 4c in 36% yield as a yellow oil. IR (CCl4)
(cm–1): 2995 (s), 2930 (s), 2873 (m), 1797 (br), 1735 (s),
1588 (m), 1490 (s), 1462 (m), 1434 (m), 1371 (m), 1278
Pyrazole 12: The spectra of this compound matched those
reported previously (10).
2-(o-Bromophenoxy)-2-(p-chlorophenoxy)-5,5-dimethyl-
∆3-1,3,4-oxadiazoline (5d)
This compound was obtained in 30% yield as a yellow oil.
IR (CCl4) (cm–1): 2996 (m), 1584 (m), 1550 (m), 1488 (s),
1476 (s), 1443 (m), 1209 (br), 1155 (br), 1108 (s), 1086 (s),
1
1031 (m), 1014 (m). H NMR (200 MHz, CDCl3) δ: 1.33 (s,
6H), 6.99–7.55 (m, 8H). 13C NMR (75 MHz, CDCl3) δ:
22.5, 23.7, 116.4, 122.4, 122.8, 123.6, 126.0, 128.0, 129.2,
130.5, 133.5, 135.7, 148.8, 149.9.
1
(m), 1231 (br), 1013 (m), 985 (m). H NMR (200 MHz,
CDCl3) δ: 1.40 (s, 3H, Me), 1.67 (s, 3H, Me), 2.08 (s, 3H,
COMe), 7.14–7.30 (m, 4H, Ph). 13C NMR (75 MHz,
CDCl3) δ: 21.3, 22.7, 24.2, 123.0, 123.8, 129.3, 130.4,
133.0, 150.1, 165.9.
Thermolysis of 5d
The general procedure afforded o-bromophenyl p-chloro-
phenyl carbonate 6d (23%), triester 10d (38%), and pyrazole
12 (23%).
2-(p-Chlorophenoxy)-2-(o-iodophenoxy)-5,5-dimethyl-∆3-
1,3,4-oxadiazoline (5c)
A solution of 4c (1.81g, 6.36 mmol) and 2-iodophenol
(1.54 g, 7.00 mmol) in CH2Cl2 (60 mL) containing catalytic
trifluoroacetic acid was heated at reflux for 24 h. Pure 5c
was obtained by means of flash column chromatography
(5% EtOH–hex) as a yellow oil, in 43% yield: IR (CCl4)
(cm–1): 1584 (m), 1550 (m), 1486 (s), 1469 (m), 1209 (s),
1155 (s), 1105 (m), 1087 (s), 1014 (m). 1H NMR (200 MHz,
CDCl3) δ: 1.34 (s, 3H, Me), 1.37 (s, 3H, Me), 6.80–7.78 (m,
8H, Ar). 13C NMR (75 MHz, CDCl3) δ: 23.5, 23.7, 90.4,
121.4, 122.3, 123.2, 123.8, 126.2, 129.2, 130.5, 135.7,
139.6, 149.9, 151.5.
o-Bromophenyl p-chlorophenyl carbonate (6d)
This compound was obtained in in 23% yield as a colour-
less solid; mp 98.5–99.5°C. IR (CCl4) (cm–1): 1784 (s), 1488
(m), 1476 (m), 1229 (br), 1194 (s), 1091 (m). 1H NMR
(200 MHz, CDCl3) δ: 7.18–7.65 (m). 13C NMR (75 MHz,
CDCl3) δ: 116.0, 122.4, 123.3, 128.2, 128.9, 129.8, 132.1,
133.8, 148.3, 149.6, 150.9. EI-MS m/z (%): 330 (M+, 10),
328 (M+, 40), 326 (M+, 28), 247 (14), 168 (100), 155 (37),
143 (20), 111 (63), 75 (66), 63 (66). CI-MS (NH3) m/z (%):
348 ([M + 18]+, 25), 346 ([M + 18]+, 100), 344 ([M + 18]+,
75). EI-HRMS m/z calcd. for C13H879Br35ClO3: 325.9345;
found: 325.9347.
Thermolysis of 5c in the presence of DMAD
Thermolysis of 5c (0.28 g, 0.63 mmol) in the presence of
DMAD (0.11 g, 0.77 mmol) as described in the general pro-
cedure gave carbonate 6c, aromatic substitution product 10c,
and pyrazole 12.
(E)-o-Bromophenylethenetricarboxylic acid 1,2-dimethyl
p-chlorophenyl ester (10d)
This compound was obtained in 38% yield as a yellow oil.
IR (CCl4) (cm–1): 1740 (br), 1487 (m), 1436 (m), 1258 (m),
1
1230 (s), 1197 (s), 1092 (m), 1072 (m), 1013 (m). H NMR
(200 MHz, CDCl3) δ: 3.82 (s, 3H, OMe), 3.95 (s, 3H, OMe),
6.73–7.61 (m, 8H, Ar). 13C NMR (75 MHz, CDCl3) δ: 53.5
(coincident OMe signals), 116.8, 122.4, 127.6, 129.6, 130.2,
130.9, 131.9, 133.0, 135.1, 148.3, 161.3, 164.0, 165.1. EI-
MS m/z (%): 423 ([M – OMe]+, 4), 421 ([M – OMe]+, 4),
375 ([M – Br]+, 4), 373 ([M – Br]+, 12), 327 ([M –
OC6H4Cl]+, 98), 325 ([M – OC6H4Cl]+, 100), 299 (58), 297
(58), 246 (31), 209 (92), 207 (92), 128 (62), 99 (90), 59
(77). CI-MS (NH3) m/z (%): 474 ([M + 18]+, 25), 472 ([M +
18]+, 100), 470 ([M + 18]+, 75).
p-Chlorophenyl o-iodophenyl carbonate (6c)
This compound was obtained in 30% yield as a colourless
solid; mp 81–82°C. IR (CCl4) (cm–1): 1782 (s), 1549 (m),
1488 (m), 1469 (m), 1225 (br), 1190 (s), 1090 (m),
1
1016 (m), . H NMR (200 MHz, CDCl3) δ: 6.99–7.88 (m).
13C NMR (75 MHz, CDCl3) δ: 89.7, 122.3, 128.3, 129.7,
131.9, 139.7, 149.4, 150.8, 151.0. EI-MS m/z (%): 376 (M+,
5), 374 (M+, 14), 247 (13), 203 (26), 168 (100), 139 (20),
111 (52), 82 (26), 76 (74), 63 (60). EI-HRMS m/z calcd. for
C13H835ClIO3: 373.9207; found: 373.9213.
(E)-o-Iodophenylethenetricarboxylic acid 1,2-dimethyl
p-chlorophenyl ester (10c)
This compound was obtained in 38% yield as a yellow oil.
IR (CCl4) (cm–1): 1738 (br), 1487 (m), 1435 (m), 1278 (m),
1257 (m), 1229 (s), 1197 (s), 1092 (m), 1074 (m), 1013 (s).
1H NMR (200 MHz, CDCl3) δ: 3.82 (s, 3H, OMe), 3.96 (s,
3H, OMe), 6.70–7.90 (m, 8H, Ar). 13C NMR (75 MHz,
2-(o-Iodophenoxy)-2-phenoxy-5,5-dimethyl-∆3-1,3,4-
oxadiazoline (5e)
A solution of 2-acetoxy-2-phenoxy-5,5-dimethyl-∆3-1,3,4-
oxadiazoline (4a) (2.69 g, 0.0108 mol) and o-iodophenol
(2.84 g, 0.0129 mol) in CH2Cl2 (60 mL) containing catalytic
trifluoroacetic acid was heated at reflux for 24 h. 2-(o-Iodo-
phenoxy)-2-phenoxy-5,5-dimethyl-∆3-1,3,4-oxadiazoline (5e)
© 2002 NRC Canada

Lu and Warkentin
233
was obtained by means of flash column chromatography (5%
EtOH–hex) as a yellow oil, in 38% yield. IR (CCl4) (cm–1):
3070 (m), 2995 (m), 1769 (m), 1593 (m), 1492 (s), 1469 (s),
1440 (m), 1383 (w), 1369 (m), 1203 (br), 1156 (br), 1105
gether and the ratio was calculated from integration of the
1H NMR signals.
(E)-o-Methylphenylethenetricarboxylic acid 1,2-dimethyl
phenyl ester (10b) and (E)-phenylethenetricarboxylic
acid 1,2-dimethyl o-methylphenyl ester (11b)
1
(br), 1021 (m), 969 (m). H NMR (200 MHz, CDCl3) δ: 1.25
(s, 3H, Me), 1.38 (s, 3H, Me), 6.83–7.78 (m, 9H, Ar). 13C
NMR (75 MHz, CDCl3) δ: 23.6, 23.8, 90.6, 121.5, 122.2,
122.8, 125.1, 125.4, 126.2, 129.2, 136.1, 139.6, 151.3, 151.9.
These were obtained as a yellow liquid (47% combined
yield) in the ratio 1:0.9 by 1H NMR. IR (CCl4) (cm–1):
1
1742 (s), 1265 (m), 1231 (s), 1191 (m). H NMR (200 MHz,
CDCl3) (composite spectrum) δ: 1.97 (s, 2.6H, o-C6H4CH3),
2.39 (s, 3H, o-C6H4CH3), 3.85 (s, 3H, OMe), 3.90 (s, 5.6H,
OMe), 3.92 (s, 2.6H, OMe), 6.54–7.51 (m, 16.8H, ArH). 13C
NMR (50.3 MHz, C6D6) (composite spectrum) δ: 15.7, 19.8,
53.2, 121.1, 126.0, 126.4, 126.5, 126.9, 128.0, 128.4, 129.1,
129.5, 129.7, 130.3, 130.6, 131.3, 132.8, 136.5, 148.2, 148.7,
149.9, 162.5, 163.0, 166.6, 167.2. EI-MS m/z (%): 356 ([M +
2]+, 6), 323 ([M – OMe]+, 10), 261 ([M – OPh]+, 67), 247
([M – OC6H4Me]+, 100), 233 (73), 219 (53), 189 (30), 175
(20), 143 (43), 129 (87), 115 (70), 91 (22), 65 (35). CI-MS
(NH3) m/z (%): 372 ([M + 18]+, 65), 354 (M+, 100).
Thermolysis of 2-(o-iodophenoxy)-5,5-dimethyl-2-phen-
oxy-∆3-1,3,4-oxadiazoline (5e) with DMAD
The general procedure gave o-iodophenyl phenyl carbon-
ate (6e), the ester from migration of the o-iodophenyl group
(10e), and pyrazole 12 (16%).
o-Iodophenyl phenyl carbonate (6e)
The carbonate was a clear oil obtained in 20% yield. IR
(CCl4) (cm–1): 3071 (m), 1788 (br), 1594 (m), 1494 (s),
1469 (s), 1441 (m), 1238 (br), 1220 (br), 1186 (br), 1163
1
(m), 1044 (m), 1022 (m), 1007 (m). H NMR (200 MHz,
CDCl3) δ: 7.02–7.43 (m). 13C NMR (75 MHz, CDCl3) δ:
89.9, 121.0, 122.6, 126.6, 128.3, 129.8, 129.9, 139.8, 151.2,
151.3. EI-MS m/z (%): 340 (M+, 16), 220 (15), 213 (17),
169 (46), 141 (47), 84 (68), 77 (100), 51 (43). HRMS calcd.
for C13H9IO3: 339.9596; found: 339.9602.
o-Methylphenyl phenyl carbonate (6b)
This compound was isolated as a yellow liquid in 31%
yield. IR (CCl4) (cm–1): 1781 (s), 1493 (m), 1232 (br),
1
1172 (s), 1113 (m). H NMR (200 MHz, CDCl3) δ: 2.32 (s,
3H, Me), 7.19–7.45 (m, 9H, ArH). 13C NMR (50.3 MHz,
C6D6) δ: 16.1, 121.0, 121.4, 126.4, 126.7, 127.2, 129.7,
130.1, 131.5, 149.7, 151.2, 152.0, 159.3. EI-MS m/z (%):
229 ([M + 1]+, 10), 228 (M+, 27), 183 (13), 107 (35), 91
(100), 77 (95), 65 (73). CI-MS (NH3) m/z (%): 246 ([M +
18]+, 100).
(E)-o-Iodophenylethenetricarboxylic acid 1,2-dimethyl
phenyl ester (10e)
This compound was obtained as a yellow oil in 45% yield.
IR (CCl4) (cm–1): 2958 (s), 2929 (m), 2660 (m), 1739 (br),
1550 (m), 1463 (m), 1435 (m), 1256 (m), 1231 (s), 1192 (s),
1012 (m). 1H NMR (200 MHz, CDCl3) δ: 3.81 (s, 3H,
OMe), 3.96 (s, 3H, OMe), 6.74–7.90 (m, 9H, Ar). 13C NMR
(75 MHz, CDCl3) δ: 53.5, 96.7, 121.1, 126.5, 128.3, 129.6,
130.6, 133.7, 139.3, 146.4, 149.9, 161.3, 164.2, 164.9. EI-
MS m/z (%): 435 ([M – OMe]+, 2), 373 ([M – I]+, 67), 339
(93), 255 (60), 246 ([M – OPh]+, 100), 215 (80), 173 (40),
128 (100), 65 (100), 59 (78). CI-MS (NH3) m/z (%): 484
([M + 18]+, 100), 467 ([M + 1]+, 30).
5,5-Dimethyl-2-(p-methylphenoxy)-2-phenoxy-∆3-1,3,4-
oxadiazoline (5a)
This compound was isolated as a clear oil. IR (CCl4) (cm–1):
3039 (m), 2994 (s), 2939 (m), 1780 (m), 1593 (s), 1507 (s),
1494 (s), 1458 (m), 1383 (m), 1288 (m), 1087 (br), 989 (m).
1H NMR (200 MHz, CDCl3) δ: 1.21 (s, 6H), 2.27 (s, 3H),
7.07–7.29 (m, 9H). 13C NMR (75 MHz, CDCl3) δ: 20.6, 23.5,
121.3, 122.1, 124.8, 129.1, 129.5, 134.5, 136.1, 149.4, 151.8.
5,5-Dimethyl-2-(o-methylphenoxy)-2-phenoxy ∆3-1,3,4-
oxadiazoline (5b)
Thermolysis of 5a in the presence of DMAD
Thermolysis of 5a (0.8 g, 2.28 mmol) in the presence of
DMAD (0.388 g, 2.73 mmol) in 20 mL of dried benzene, re-
moval of the solvent by rotary evaporation, and flash column
chromatography followed by radial chromatography gave the
following products:
A solution of the 2-acetoxy-2-phenoxy oxadiazoline 4a
(0.88 g, 3.52 mmol) and o-methylphenol (1.14 g,
10.7 mmol) in CH2Cl2 (60 mL) containing catalytic trifluor-
oacetic acid was heated at reflux for 24 h. 2-(o-Methylphen-
oxy)-2-phenoxy oxadiazoline (5b) was separated by flash
column chromatography (5% EtOH–hex) as a yellow oil in
53% yield. IR (CCl4) (cm–1): 3067 (m), 2994 (m), 2939 (m),
1592 (m), 1492 (s), 1460 (m), 1383 (m), 1369 (m), 1207
p-Methylphenyl phenyl carbonate (6a) (15)
This compound was isolated in 30% yield. 1H NMR
(200 MHz, CDCl3) δ: 2.33 (s, 3H, p-C6H4CH3), 7.11–7.43
(m, 9H, ArH). 13C NMR (50.3 MHz, C6D6) δ: 20.9, 120.7,
121.0, 126.3, 129.6, 130.1, 136.1, 148.9, 151.1, 152.4. EI-
MS m/z (%): 228 (M+, 90), 184 (40), 107 (17), 91 (92), 77
(100), 65 (64). CI-MS (NH3) m/z (%): 246 ([M + 18]+, 100),
228 (M+, 27).
1
(br), 1156 (br), 1121 (br), 989 (m). H NMR (200 MHz,
CDCl3) δ: 1.13 (s, 3H, Me), 1.23 (s, 3H, Me), 2.21 (s, 3H, o-
C6H4CH3), 7.00–7.28 (m, 9H, ArH). 13C NMR (50.3 MHz,
C6D6) δ: 16.8, 23.4, 24.8, 121.3, 122.4, 122.9, 125.1, 125.3,
126.4, 129.2, 131.1, 131.8, 136.8, 150.1, 151.8.
Thermolysis of 5,5-dimethyl-2-(o-methylphenoxy)-2-
phenoxy-∆3-1,3,4-oxadiazoline (5b) in the presence of
DMAD
The general procedure gave products of aromatic substitu-
tion that could not be separated. They were identified to-
(E)-p-Methylphenylethenetricarboxylic acid 1,2-dimethyl
phenyl ester (10a) and (E)-phenylethenetricarboxylic
acid 1,2-dimethyl p-methylphenyl ester (11a)
These products were obtained as a mixture of isomers, in
© 2002 NRC Canada

234
Can. J. Chem. Vol. 80, 2002
1
cycloaddition. Vol. 2. Edited by D.P. Curran. JAI Press,
Greenwich, CT. 1990. p. 147; (d) M.S. Baird, H.L. Fitton,
and L. Rajaram. J. Chem. Soc. Perkin Trans.1, 1633 (1994);
(e) J.R. Al Dulayymi, M.S. Baird, L. Rajaram, and W. Clegg.
J. Chem. Res. (S), 344 (1994).
the ratio 4.5:1 (by H NMR) as a yellow oil, in 42% yield.
1H NMR (200 MHz, CDCl3) δ: 2.29 and 2.38 (2s, overall
3H, p-C6H4CH3), 3.90 (s, 6H, OMe), 6.62–7.53 (m, 9H,
ArH). 13C NMR (50.3 MHz, C6D6) δ: 21.0, 53.2, 117.3,
120.8, 121.2, 127.9, 129.1, 129.6, 129.8, 130.1, 130.6, 132.9,
136.2, 147.9, 148.2, 162.9, 163.4, 167.2. EI-MS m/z (%): 356
([M + 2]+, 3), 323 ([M – OMe]+, 3), 261 ([M – OC6H5]+, 67),
247 ([M – OC6H4Me]+, 100), 233 (73), 129 (36), 107 (9), 93
(2), 77 (32), 59 (28). CI-MS (NH3) m/z (%): 374 ([M + 20]+,
25), 373 ([M + 19]+, 100), 372 ([M + 18]+, 31), 355 ([M +
1]+, 28), 354 (27).
3. X. Lu and J. Warkentin. Tetrahedron Lett. 40, 1483 (1999).
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6. (a) M. Salim and A. Capretta. Tetrahedron, 56, 8064 (2000);
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63, 9828 (1998).
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(2001).
8. K. Kassam, D.L. Pole, M. El-Saidi, and J. Warkentin. J. Am.
Chem. Soc. 116, 1161 (1994).
Acknowledgments
The authors gratefully acknowledge the financial support
of the Natural Sciences and Engineering Research Council
of Canada (NSERC) and the assistance of Mr. Brian Sayer
and Dr. Kirk Green with NMR spectroscopy and mass spec-
trometry.
9. W.B. Smith. J. Org. Chem. 60, 7456 (1995).
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References
1. For a recent example of a further reaction of a cyclopropene
intermediate, see (a) X. Lu and J. Warkentin. Org. Lett. 2,
3501 (2000); (b) X. Lu and J. Warkentin. Org. Lett. 3, 143
(2001).
2. For example, see: (a) M.S. Baird, S.R. Buxton, and J.S. Whit-
ley. Tetrahedron Lett. 25, 1509 (1984); (b) J. Al Dulayymi,
M.S. Baird, and W. Clegg. Tetrahedron Lett. 29, 6149 (1988);
(c) D.L. Boger and C.E. Brotherton-Pleiss. In Advances in
© 2002 NRC Canada