Syntheses and pyrolyses of benzofuran analogues of α-oxo-o- quinodimethane. A study on vinylcarbene-cyclopropene rearrangement

Article abstract of DOI:10.1021/jo702704e

(Chemical Equation Presented) Flash vacuum pyrolyses (FVP) of benzoic 3-methyl-2-benzofurancarboxylic anhydride (12) and benzoic 2-methyl-3- benzofurancarboxylic anhydride (13) at 550°C and ca. 10^-2 torr both give methylenebenzocyclobutenone (21) as the major product and indenone (22) as the minor one. A mechanism involving generation of α-oxo-o- quinodimethane 11 as the primary pyrolysis product from FVP of 13, followed by elimination of a CO molecule to give carbene 24, which undergoes a vinylcarbene-cyclopropene rearrangement and a ring contraction of the resulting carbene 23, is proposed to account for the observed results. The proposed mechanism is further supported by a deuterium-labeling study on FVP of (2-benzofuryl)methyl-α,α-d₂ benzoate (28-d₂).

Full text of DOI:10.1021/jo702704e

Syntheses and Pyrolyses of Benzofuran Analogues of
r-Oxo-o-quinodimethane. A Study on Vinylcarbene-Cyclopropene
Rearrangement
Pen-Wen Tseng, Su-Wen Yeh, and Chin-Hsing Chou*
Department of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-Sen
UniVersity, Kaohsiung, Taiwan 804, R.O.C.
ch-chou@mail.nsysu.edu.tw
ReceiVed December 20, 2007
Flash vacuum pyrolyses (FVP) of benzoic 3-methyl-2-benzofurancarboxylic anhydride (12) and benzoic
2-methyl-3-benzofurancarboxylic anhydride (13) at 550 °C and ca. 10-2 torr both give methyleneben-
zocyclobutenone (21) as the major product and indenone (22) as the minor one. A mechanism involving
generation of R-oxo-o-quinodimethane 11 as the primary pyrolysis product from FVP of 13, followed by
elimination of a CO molecule to give carbene 24, which undergoes a vinylcarbene-cyclopropene
rearrangement and a ring contraction of the resulting carbene 23, is proposed to account for the observed
results. The proposed mechanism is further supported by a deuterium-labeling study on FVP of (2-
benzofuryl)methyl-R,R-d2 benzoate (28-d2).
Introduction
homophthalic anhydride (3)5 or o-toluyl chloride (4),6 and once
it is generated, 2 converts to the more stable benzocyclobutenone
(5).
o-Quinodimethane (1), since it was first recognized as a
reactive intermediate in 1957,1 has been actively investigated
from theoretical, physical, physical organic, and synthetic organic
viewpoints.2–4
The development of 1 has been extended to R-oxo-o-
quinodimethane (2). 2 can be prepared from pyrolysis of either
Previously, we have synthesized the benzofuran analogue of
1, namely, 2,3-dimethylene-2,3-dihydrofuran (6), from flash
vacuum pyrolysis (FVP) of (2-methyl-3-benzofuryl)methyl
benzoate (7).7 6 is stable below -40 °C, and at room temp-
erature, 6 dimerized to give a [4 + 2] dimer 8 and a [4 + 4]
dimer 9. The reason for using benzoate instead of acetate as
the pyrolysis precursor for our study is that benzoic acid,
generated as the byproduct from FVP of 7, can easily be
separated from the target compound 6 by a pyrolysis setup that
has been described previously.7
* Address correspondence to this author. Fax: +886-7-5253909.
(1) Cava, M. P.; Napier, D. R. J. Am. Chem. Soc. 1957, 79, 1701–1705.
(2) Cava, M. P.; Deana, A. A.; Muth, K. J. Am. Chem. Soc. 1959, 81, 6458–
6460.
(3) Jensen, F. R.; Coleman, W. E. J. Am. Chem. Soc. 1958, 80, 6149.
(4) For leading references see: McCullough, J. J. Acc. Chem. Res. 1980, 13,
270–276.
On the basis of our work on the preparation of 6, we
anticipated that the previously unknown benzofuran analogues
(5) Spangler, R. J.; Kim, J. H. Tetrahedron Lett. 1972, 13, 1249–1251.
(6) Schiess, P.; Heitzmann, P. Angew. Chem., Int. Ed. Engl. 1977, 16, 469–
470.
(7) Chou, C. H.; Trahanovsky, W. S. J. Org. Chem. 1986, 51, 4208–4212.
J. Org. Chem. 2008, 73, 3481–3485 3481
10.1021/jo702704e CCC: $40.75
Published on Web 03/20/2008
2008 American Chemical Society

Tseng et al.
SCHEME 1
SCHEME 2
of 2, (3-methylene-3H-benzofuran-2-ylidene)methanone (10)
and (2-methylene-2H-benzofuran-3-ylidene)methanone (11),
could be prepared from FVP of benzoic 3-methyl-2-benzo-
furancarboxylic anhydride (12) and benzoic 2-methyl-3-benzo-
furancarboxylic anhydride (13), respectively.
The FVP of 12 was performed at 550 °C and ca. 10-2 torr,
using the method previously reported.11 The products were
1
collected in CDCl3 from the cold trap. Low-temperature H
NMR spectroscopy7 at -70 °C revealed that no target compound
10 was obtained. After warming the solution to room temper-
ature, quantitative 1H NMR analysis, using dibromomethane as
an integration standard, indicated that methylenebenzocy-
clobutenone (21) was obtained as the major product in 48%
yield, along with indenone (22) as a minor product in 4% yield,
and some polymers. The pyrolysis temperature at 550 °C and
ca. 10-2 torr appeared to be the optimum reaction conditions
for our study. FVP of 12 at temperatures lower than 500 °C
would leave unreacted starting materials, whereas FVP of 12
at temperatures higher than 600 °C gave a lower yield of 21.
The formation of 21 and 22 can be rationalized by a mechanism
proposed as shown in Scheme 2.
To study the chemistry of 10 and 11, we have synthesized
and pyrolyzed anhydrides 12 and 13. The results of this
investigation are presented herein.
Under the pyrolysis conditions, a [3 + 3] sigmatropic
rearrangement from 12 followed by elimination of a benzoic
acid molecule is proposed to give the primary pyrolysis product
10. A sequential elimination of a CO molecule from 10 is
proposed to produce carbene 23, a reaction for which there is
good precedent.12 A 1,2-phenyl shift13 from 23 is proposed to
give 21. Rearrangement of 21 under pyrolysis conditions is
known to give 22.9
Results and Discussion
The FVP of 13, under the same pyrolysis conditions,
unexpectedly gave the same pyrolysis products, 21 (50% yield)
and 22 (5% yield). Our original expectation was that, as shown
in Scheme 3, carbene 24, generated from the FVP of 13, would
undergo a ring-opening reaction to give triene 25. However,
the formation of 21 and 22 from 13 suggests that carbene 24,
instead of undergoing a process that destroys the aromaticity of
Anhydrides 12 and 13 were prepared from reactions of
benzoyl chloride with the corresponding acids, 3-methyl-2-
benzofurancarboxylic acid (14) and 2-methyl-3-benzofurancar-
boxylic acid (15), respectively.
Acid 14 was prepared from hydrolysis of ethyl 3-methyl-
2-benzo[b]furoate (16). 16 was prepared from reaction of
2-hydroxyacetophenone (17) with bromoacetate (18) followed
by intramolecular Aldol-condensation of the resulting 198
(Scheme 1).
(9) Trahanovsky, W. S.; Amah, A. N.; Cassady, T. J. J. Am. Chem. Soc.
1984, 106, 2696–2698.
(10) Koelsch, C. F.; Whitney, A. G. J. Am. Chem. Soc. 1941, 63, 1762.
(11) Trahanovsky, W. S.; Ong, C. C.; Pataky, J. G.; Weitl, F. L.; Muellen,
P. W.; Clardy, J. C.; Hansen, R. S. J. Org. Chem. 1971, 36, 3575–3579.
(12) Brown, R. F. C.; Eastwood, F. W.; McMullen, G. L. Aust. J. Chem.
1977, 30, 179–193.
Acid 15 was prepared by the methylation of 3-benzofuran-
carboxylic acid (20).7 Acid 20 was prepared by a known
procedure starting from ethyl phenoxyacetate.9,10
(13) Brown, R. F. C.; Eastwood, F. W.; Lim, S. T.; McMullen, G. L. Aust.
J. Chem. 1976, 29, 1705–1712.
(8) Foster, R. T.; Robertson, A.; Bushra, A. J. Chem. Soc. 1948, 2254–2260.
3482 J. Org. Chem. Vol. 73, No. 9, 2008

Vinylcarbene-Cyclopropene Rearrangement
SCHEME 3
SCHEME 4
SCHEME 5
the benzene ring in 24 to give 25, undergoes a vinylcarbene-
cyclopropene rearrangement,14 involving cyclopropene 26, to give
carbene 23, which then leads to the formation of 21 and 22.
To study the stability of proposed intermediates 23, 24, and
26 from FVP of 13, we have carried out molecular orbital
calculations at the B3LYP/6-31G(d) level of DFT for 26, and
carbenes 23 and 24 in multiplicities of both singlet and triplet
states. It is desirable to understand the possibility of formation
for the intermediates from the computational chemistry. The results
of calculation indicate that the ground state carbenes 23 and 24
are singlet, and, as shown in Figure 1, the singlet carbene 23 is
indeed 7.07 kcal/mol more stable than the singlet carbene 24.
A mechanism to account for the formations of 21 and 22
and their deuterated derivatives 21-d2 and 22-d2 from FVP of
28 and 28-d2 is proposed and shown as Scheme 6.
The deuterium-labeling study not only supports the vinyl-
carbene-cyclopropene rearrangement, but also rules out the
possibility of elimination of a benzoic acid from 28-d2 as the
initial step. For such a mechanism, FVP of 28-d2 would lead to
the formation of a monodeuterated methylenebenzocyclobuten-
one 21-d as shown in Scheme 7.
In summary, our results support the involvement of a
vinylcarbene-cyclopropene rearrangement in the formation of
21 and 22 from the FVP of 13 and 28 (Scheme 8). We are
currently extending our study to the other heteroaromatic
systems.
FIGURE 1. Schematic representation of stability of intermediate 26
and singlet carbenes 23and 24 based on the DFT calculations.
Compound 21was first prepared by Trahanovsky and co-
workers.9 They reported that FVP of (3-benzofuryl)methyl
benzoate (27) gives 21, presumably involving carbene 23 as
the reaction intermediate (Scheme 4).
Experimental Section
Benzoic 3-Methyl-2-benzofurancarboxylic Anhydride (12).
Anhydride 12 was prepared in 90% yield from reaction of benzoyl
chloride with 3-methyl-2-benzofurancarboxylic acid (14). 12: IR
(CHCl3, cm-1) 1730 (CdO), 1690 (CdO), 1090 (CsO); 1H NMR
(CDCl3) δ 8.22–7.53 (m, 9H, arom), 2.69 (s, 3H, CH3); 13C NMR
(CDCl3) δ 162.1 (C), 161.8 (C), 155.4 (C), 154.7 (C), 139.3 (C),
134.4 (C), 134.3 (CH), 130.4 (C), 130.3 (CH), 130.1 (CH), 128.7
(CH), 123.4 (CH), 121.3 (CH), 112.1 (CH), 9.5 (CH3); high-
The involvement of carbene 23 in the FVP of 27, along with
the aforementioned vinylcarbene-cyclopropene rearrangement
mechanism for conversion of 24 to 23, led us to propose that
FVP of (2-benzofuryl)methyl benzoate (28) would also give 21.
To investigate the pyrolytic chemistry of 28, the prepara-
tions and pyrolyses of 28, and its deuterated derivative, (2-
benzofuryl)methyl-R,R-d2 benzoate (28-d2) were performed.
Compounds 28 and 28-d2 were prepared by either LiAlH4 or
LiAlD4 reduction of benzofuran-2-carboxylic acid (29)15
followed by esterification of the resulting alcohol 30 or 30-
d2 with benzoyl chloride in the presence of triethylamine16
as outlined in Scheme 5.
In agreement with the proposed mechanism, FVP of 28, at
550 °C and ca. 10-2 torr, gave 21 in 40% yield and 22 in 5%
yield, whereas FVP of 28-d2, under the same pyrolysis condi-
tions, gave R,R-d2-methylenecyclobutenone (21-d2) and 2,3-
dideuterioindenone (22-d2) in similar yields.
(14) Wentrup, C. Top. Curr. Chem. 1976, 62, 184–187.
(15) Winberg, H. E.; Fawcett, F. S.; Mochel, W. E.; Theobald, C, W. J. Am.
Chem. Soc. 1960, 82, 1428–1435.
(16) Trahanovsky, W. S.; Cassady, T. J.; Woods, T. L. J. Am. Chem. Soc.
1981, 103, 6691–6695.
(17) Chou, C. H.; Trahanovsky, W. S. J. Am. Chem. Soc. 1986, 108, 4138–
4144.
(18) Wasson, B. K.; Hamel, P.; Rooney, C. S. J. Org. Chem. 1977, 42, 4265–
4266.
(19) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley: New
York, 1967; Vol. 1, p 584.
(20) Kundu, N. G.; Pal, M.; Mahanty, J. S.; De, M. J. Chem. Soc., Perkin
Trans. 1 1997, 19, 2815–2820.
J. Org. Chem. Vol. 73, No. 9, 2008 3483

Tseng et al.
SCHEME 6
SCHEME 7
7.58–7.22 (m, 7H, arom), 6.84 (s, 1H, arom), 5.45 (s, 2H, CH2);
13C NMR (CDCl3) δ 166.1 (C), 155.2 (C), 151.9 (C), 133.2 (CH),
129.8 (C), 129.7 (CH), 128.3 (CH), 127.9 (C), 124.8 (CH), 122.9
(CH), 121.3 (CH), 111.4 (CH), 107.0 (CH), 59.0 (CH2); high-
resolution mass spectrum, calcd for C16H12O3 252.0787, measured
252.0785.
(2-Benzofuryl)methyl-r,r-d2 Benzoate (28-d2). Benzoate 28-
d2 was prepared in 90% yield by esterification of (2-benzofuryl)-
methyl-R,R-d2 alcohol (30-d2) with benzoyl chloride. 28-d2: IR
1
(CHCl3, cm-1) 1710 (CdO), 1250 (CD2), 1180 (CsO); H NMR
(CDCl3) δ 8.81–8.05 (m, 2H, arom), 7.58–7.22 (m, 7H, arom), 6.84
(s, 1H, arom); 13C NMR (CDCl3) δ 166.1 (C), 155.2 (C), 151.9
(C), 133.2 (CH), 129.8 (C), 129.7 (CH), 128.3 (CH), 127.9 (C),
124.8 (CH), 122.9 (CH), 121.3 (CH), 111.4 (CH), 107.1 (CH); high-
resolution mass spectrum, calcd for C16H10D2O3 254.0912, measured
254.0916.
SCHEME 8
General Pyrolysis Procedure. A tube furnace was used for our
study. The pyrolysis temperature was measured at the center of
the pyrolysis tube. The furnace was maintained at 550 °C. A sample
of the anhydride or ester in a Pyrex boat was placed into the sam-
ple chamber and the system was evacuated to ca. 10-2 torr. The
sample chamber was heated to ca. 100 °C during the pyrolysis. A
condenser inserted between the furnace and the liquid-nitrogen-
cooled trap to collect the benzoic acid formed as byproduct was
cooled to ca. 0 °C. During the pyrolysis, a 1:1 ratio of CS2/CDCl3
solution was deposited into the trap through a sidearm. Upon
completion of the pyrolysis nitrogen was introduced into the system
and the trap was warmed to –78 °C and collected in NMR tubes,
maintained at –78 °C, for low- temperature NMR measurements.
The product solution was then warmed to room temperature and
the products were purified for identification.
PyrolysisofBenzoic3-Methyl-2-benzofurancarboxylicAnhy-
dride (12). 12 (930 mg, 3.32 mmol) was pyrolyzed at 550 °C and
ca. 10-2 torr in the normal manner for 3 h. 1 mL of CDCl3 and a
weighed amount of dibromomethane as an NMR integration
standard were added to the product trap. 1H NMR analysis of this
mixture showed the presence of 21 (207 mg, 1.60 mmol, 48%)
and 22 (17.3 mg, 0.133 mmol, 4%). To separate 21 from 22, an
amine-acid method9 was employed: 1 mL of anhydrous ether was
added to the product. To the mixture was added 10.0 mg (0.15
mmol) of pyrrolidine in anhydrous ether. After 30 s 8.97 mg (0.15
mmol) of acetic acid in ether was added to the mixture. After 2
min 1.0 g (11.9 mmol) of NaHCO3 was added to the mixture, and
the mixture was stirred at room temperature for 2 h. The mixture
was then separated by thin-layer chromatography with a mixture
resolution mass spectrum, calcd for C17H12O4 280.0738, measured
280.0740. Anal. Calcd: C, 72.86; H, 4.29. Found: C, 72.65; H, 4.30.
Benzoic 2-Methyl-3-benzofurancarboxylic Anhydride (13). A
procedure described for the preparation of 12 was followed for the
reaction of 2-methyl-3-benzofurancarboxylic acid (15) and benzoyl
chloride to give 92% yield of 13: IR (CHCl3, cm-1) 1725 (CdO),
1683 (CdO), 1105 (CsO); 1H NMR (CDCl3) δ 8.19–7.28 (m, 9H,
arom), 2.84 (s, 3H, CH3); 13C NMR (CDCl3) δ 166.9 (C), 166.7
(C), 162.3 (C), 162.2 (C), 159.5 (C), 153.7 (C), 153.7 (C), 134.5
(CH), 130.5 (CH), 128.9 (CH), 124.9 (CH), 124.4 (CH), 121.3 (CH),
111.1 (CH), 14.9 (CH3); high-resolution mass spectrum, calcd for
C17H12O4 280.0732, measured 280.0735. Anal. Calcd: C, 72.86;
H, 4.29. Found; C, 72.60; H, 4.39.
(2-Benzofuryl)methyl Benzoate (28). Benzoate 28 was prepared
in 90% yield by esterification of (2-benzofuryl)methyl alcohol (30)
with benzoyl chloride. 28: IR (CHCl3, cm-1) 1720 (CdO), 1460
(CH2), 1150 (CsO); 1H NMR (CDCl3) δ 8.08–8.05 (m, 2H, arom),
3484 J. Org. Chem. Vol. 73, No. 9, 2008

Vinylcarbene-Cyclopropene Rearrangement
of 5% ethyl acetate in hexanes as an eluent to give 21 (80.0 mg,
19%) as a yellow oil: IR (CDCl3, cm-1) 3010 (CH2), 1770 (CdO),
torr in the normal manner for 3 h. Quantitative NMR analysis with
dibromomethane as an integration standard indicated that a 40%
yield of 21 and a 5% yield of 22 were obtained.
1
1730 (CdC); H NMR (CDCl3) δ 7.50–7.30 (m, 4H, arom), 5.47
and 5.24 (ABd, J ) 1.5 Hz, 2H, CH2); 13C NMR (CDCl3) δ 186.1
(C), 159.0 (C), 156.4 (C), 156.1 (C), 135.0 (CH), 130.2 (CH), 121.6
(C), 120.2 (CH), 102.1 (CH2); high-resolution mass spectrum, calcd
for C9H6O 130.0419, measured 130.0414. [Lit.9 21: IR (CDCl3,
Pyrolysis of (2-Benzofuryl)methyl-r,r-d2 Benzoate (28-d2). A
250 mg (0.984 mmol) quantity of 28-d2 was pyrolyzed at 550 °C
and ca. 10-2 torr in the normal manner for 3 h. Quantitative NMR
analysis with dibromomethane as an integration standard indicated
that a 42% yield of 21-d2 and a 5% yield of 22-d2 were obtained.
1
cm-1) 3010, 1770, 1740; H NMR (CDCl3) δ 7.5–7.3 (m, 4H),
5.47 (d, J )1.47 Hz, 1H), 5.24 (d, J ) 1.46 Hz, 1H); 13C NMR
(CDCl3) δ 186.1, 159.6, 156.4, 156.1, 135.0, 130.2, 121.6, 120.2,
102.1.].
1
21-d2: IR (CDCl3, cm-1) 1770 (CdO), 1730 (CdC); H NMR
(CDCl3) δ 7.50–7.30 (m, 4H, arom); high-resolution mass spectrum,
calcd for C9H4D2O 132.0419, measured 132.0414. 22-d2: IR
(CDCl3, cm-1) 1710 (CdO), 1630 (phenyl CdC), 1510 (phenyl
When 12 (510 mg, 1.82 mmol) was pyrolyzed at 700 °C and ca.
10-2 torr in the normal manner for 2 h, 22 was obtained as the
main product. Purification of the pyrolysis product by thin-layer
chromatography with a mixture of 10% ethyl acetate in hexanes as
1
CdC); H NMR (CDCl3) δ 7.44 (d, J ) 7.2 Hz, 1H, arom), 7.34
(d, J ) 6.6 Hz, 1H, arom), 7.25 (d, J ) 6.6 Hz, 1H, arom), 7.07
(d, J ) 7.2 Hz, 1H, arom); high-resolution mass spectrum, calcd
for C9H4D2O 132.0419, measured 132.0415.
an eluent gave 22 as a yellow oil (94.6 mg, 40%): IR (CDCl3, cm-1
)
3010 (phenyl CsH), 1710 (CdO), 1630 (phenyl CdC), 1510
(phenyl C)C); 1H NMR (CDCl3) δ 7.57 (dd, J ) 6.2, 0.9 Hz, 1H,
vinyl), 7.44 (d, J ) 7.2 Hz, 1H, arom), 7.34 (dd, J ) 6.6, 0.9 Hz,
1H, arom), 7.25 (d, J ) 6.6 Hz, 1H, arom), 7.07 (d, J ) 7.2 Hz,
1H, arom), 5.90 (d, J ) 6.2 Hz, 1H, vinyl); 13C NMR (CDCl3) δ
198.4 (C), 149.8 (CH), 144.6 (C), 133.7 (CH), 130.4 (C), 129.2
(CH), 127.2 (CH), 122.7 (CH), 122.2 (CH). [Lit.21 1H NMR (200
MHz, CDCl3) δ 7.56 (d, J ) 5.9 Hz, 1H), 7.45–7.04 (m, 4H), 5.89
(d, J ) 5.9 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 200.2, 151.6,
146.7, 135.6, 132.4, 131.1, 129.2, 124.6, 124.2.].
PyrolysisofBenzoic2-Methyl-3-benzofurancarboxylicAnhy-
dride (13). A 900 mg (3.21 mmol) quantity of 13 was pyrolyzed
at 550 °C and ca. 10-2 torr in a procedure described for the FVP
of 12 to give 209 mg (1.61 mmol, 50%) of 21 and 20.9 mg (0.16
mmol, 5%) of 22.
Computational Details. Density function theory (DFT) calcula-
tions at the B3LYP level were performed to obtain the total energies
of intermediate 26, and carbenes 23 and 24 in multiplicities of both
triplet and singlet states. The basis set used for C, O, and H atoms
was 6-31G(d). We have generated the theoretical geometry of 23,
24, and 26 by optimization. All the calculations were made with
the use of Gaussian 03.
Acknowledgement. We thank the National Science Council
of the Republic of China for financial support.
Supporting Information Available: Experimental proce-
dures for the syntheses of 12, 14, 15, 16, 28, 28-d2, 30, and
30-d2, computational details of 23, 24, and 26, and spectroscopic
data for 12, 13, 28, 28-d2, 21, 21-d2, 22, and 22-d2. This material
is available free of charge via the Internet at http://pubs.acs.org.
Pyrolysis of (2-Benzofuryl)methyl Benzoate (28). A 300 mg
(1.19 mmol) quantity of 28 was pyrolyzed at 550 °C and ca. 10-2
(21) Zengin, M.; Dastan, A.; Balci, M. Synth. Commun. 2001, 13, 1993–
1999.
JO702704E
J. Org. Chem. Vol. 73, No. 9, 2008 3485