Syntheses and pyrolyses of furan analogues of α-Oxo- o -quinodimethanes. Formation of methylenecyclobutenone and 1-buten-3-yne via a vinylcarbene-cyclopropene rearrangement

Article abstract of DOI:10.1021/jo201743h

Flash vacuum pyrolyses (FVP) of benzoic 2-methyl-3-furoic anhydride (12) and benzoic 3-methyl-2-furoic anhydride (13) at 550 °C and ca. 10 ^-2 Torr both give methylenecyclobutenone (16) and 1-buten-3-yne (17) as the main products. A mechanism involving generation of furan analogues of α-oxo-o-quinodimethane, 10 and 11, from FVP of 12 and 13, respectively, followed by elimination of a CO molecule to give the respective carbenes 34 and 36 is proposed. Carbenes 34 and 36 are interconvertible via a cyclopropene intermediate 35. A ring contraction from 36 will give 16, whereas a ring-opening of 34 followed by elimination of a CO molecule then leads to 17. The proposed mechanism is supported by substituent- and deuterium-labeling study on FVP of the derivatives of 12.

Full text of DOI:10.1021/jo201743h

ARTICLE
pubs.acs.org/joc
Syntheses and Pyrolyses of Furan Analogues of α-Oxo-o-
quinodimethanes. Formation of Methylenecyclobutenone and
1-Buten-3-yne via a VinylcarbeneꢀCyclopropene Rearrangement
Pen-Wen Tseng,† Chen-Yu Kung,† Hsing-Yin Chen,‡ and Chin-Hsing Chou*,†
†Department of Chemistry, National Sun Yat-Sen University, Kaohsiung, Taiwan 804, Republic of China
‡Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan 807, Republic of China
S Supporting Information
b
ABSTRACT: Flash vacuum pyrolyses (FVP) of benzoic 2-
methyl-3-furoic anhydride (12) and benzoic 3-methyl-2-furoic
anhydride (13) at 550 °C and ca. 10ꢀ2 Torr both give methyl-
enecyclobutenone (16) and 1-buten-3-yne (17) as the main
products. A mechanism involving generation of furan analogues
of α-oxo-o-quinodimethane, 10 and 11, from FVP of 12 and 13,
respectively, followed by elimination of a CO molecule to give
the respective carbenes 34 and 36 is proposed. Carbenes 34 and
36 are interconvertible via a cyclopropene intermediate 35. A
ring contraction from 36 will give 16, whereas a ring-opening of 34 followed by elimination of a CO molecule then leads to 17. The
proposed mechanism is supported by substituent- and deuterium-labeling study on FVP of the derivatives of 12.
’ INTRODUCTION
anhydride (13), respectively (eqs 1 and 2). The results of our
Since Cava and Napier1 reported the generation of the reactive
species o-quinodimethane (1) in 1957, there have been tremendous
efforts put into the study of the preparation, physical properties,
and synthetic application of 1 and its derivatives.2ꢀ4
investigation are presented herein.
The development of 1 has been extended to α-oxo-o-quinodi-
methane (2).5,6 Recently, in an attempt to synthesize the benzofuran
analogues of 2, (2-methylene-2H-benzofuran-3-ylidene)methanone
(3) and (3-methylene-3H-benzofuran-2-ylidene)methanone (4),
we have studied the pyrolytic chemistry of benzoic 2-methyl-3-
benzofurancarboxylic anhydride (5) and benzoic 3-methyl-2-
benzofurancarboxylic anhydride (6), respectively.7
’ RESULTS AND DISCUSSION
Anhydrides 12 and 13 were prepared from reactions of
benzoyl chloride with the corresponding acids, 2-methyl-3-furoic
acid (14) and 3-methyl-2-furoic acid (15), respectively (eqs 3
and 4). Acids 14 and 15 were prepared by using the methods that
have been reported previously.8,9
Flash vacuum pyrolysis (FVP)8 of 5 and 6 at 550 °C and ca.
10ꢀ2 Torr both gave methylenebenzocyclobutenone (7) as the
major product. A mechanism involving generation of 3 as the
primary pyrolysis product from FVP of 5, followed by elimination of
a CO molecule to give carbene 8, whichundergoesavinylcarbeneꢀ
cyclopropene rearrangement and a ring contraction of the resulting car-
bene 9, is proposed to account for the observed results (Scheme 1).7
In order to study the generality of the proposed vinylcarbeneꢀ
cyclopropene rearrangement, we have extended our study to the
syntheses and pyrolyses of the previously unknown furan analogue
of 2, (2-methylene-2H-furan-3-ylidene)methanone (10) and (3-
methylene-3H-furan-2-ylidene)methanone (11) from FVP of benzoic
2-methyl-3-furoic anhydride (12) and benzoic 3-methyl-2-furoic
Received: August 23, 2011
Published: September 13, 2011
r
2011 American Chemical Society
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Scheme 1
2-methyl-4-methylenecyclobutenone (29, 15% yield) and 3,4,5-
hexatrien-2-one (30, 60% yield) as the main products (eq 8). In
addition, FVP of 20 gave 2-deuterio-4-methylenecyclobutenone
(31, 15% yield) and 2-deuterio-1-buten-3-yne (32, 50% yield)
(eq 9).
The FVP of 12 was performed at 550 °C and ca. 10ꢀ2 Torr
using the method previously described.10 Pyrolysis products
were collected in CDCl3 from the cold trap. After the solution
1
was warmed to room temperature, quantitative H NMR anal-
ysis, using dibromomethane as an integration standard, indicated
that methylenecyclobutenone (16, 17% yield)11,12 and 1-buten-
3-yne (17, 55% yield) were obtained as two main products. The
pyrolysis temperature at 550 °C and ca. 10ꢀ2 Torr appeared to be
the optimum reaction conditions for our study. FVP of 12 lower
than 500 °C or higher than 600 °C all gave lower yields of 16 and
17. It is noteworthy that FVP of isolated 16 under the same
pyrolysis conditions did not give 17, a result suggesting that 16
and 17 are generated by different pathways from 12 (eq 5).
A mechanism to account for the aforementioned results is
proposed and shown as Scheme 4.
Under the pyrolysis conditions, a [3 + 3] sigmatropic re-
arrangement from 12 or its derivatives 18ꢀ20 followed by
elimination of a benzoic acid molecule is proposed to give the
primary pyrolysis product 33, a furan analogue of α-oxo-o-
quinodimethane (2). A sequential [1,5]H shift from 33 (R =
CH3, R0 = H) will lead to the stable 28. On the other hand, 33
(R = H) could eliminate a CO molecule to produce carbene 34,
a reaction for which there is good precedent.17 A ring-opening
reaction from carbene 34 (where R0 = H or D) followed by
a [1,4]H shift and elimination of a CO molecule then give 17 or
32. However, when R0 = CH3, a ring-opening reaction from
34 will give isolable 30, from which no methyl group migra-
tion was observed. Alternatively, a vinylcarbeneꢀcycpopropene
rearrangement7 would convert carbene 34, involving cyclopro-
pene 35, to carbene 36, which then leads to the formation of 16,
29, or 31.
All the pyrolysis products, except 30, are stable in solu-
tion and can be isolated and identified by their respective
spectroscopic data. Compound 30 can only survive in solution
at ꢀ78 °C and polymerized immediately upon warming to
room temperature. Nonetheless, the low-temperature 1H and
13C NMR spectral data obtained at ꢀ78 °C for the product
solution from 19 reveals the formation of 30 as the major pro-
duct from FVP of 19.
In order to study the mechanism for the formation of 16
and 17 from FVP of 12, we have carried out substituent- and
deuterium-labeling experiments by synthesizing and pyrolyzing
the derivatives of 12: benzoic 2-ethyl-3-furoic anhydride (18),benzoic
2,5-dimethyl-3-furoic anhydride (19), and benzoic 5-deuterio-2-
methyl-3-furoic anhydride (20). Anhydrides 18ꢀ20 were pre-
pared again from reactions of benzoyl chloride with the corre-
sponding acids, 2-ethyl-3-furoic acid (21), 2,5-dimethyl-3-furoic
acid (22) (eq 6), and 5-deuterio-2-methyl-3-furoic acid (23),
respectively. Acid 2113 was prepared by condensation of ethyl
3-oxopentanonate (24)14 with 2-chloroacetaldehyde followed by
hydrolysis of the resulting 2-ethyl-3-furoate (25) (Scheme 2).
Acid 22 was prepared by a method that has been previously
reported.15 Acid 23 was prepared from refluxing 3-furoic acid
(26) in basic D2O solution followed by methylation of the
resulting 2,5-dideuterio-3-furoic acid (27)16 (Scheme 3).
Additionally, the FVP of 13 performed under the same
pyrolysis conditions gave the same pyrolysis products, 16 (15%
yield) and 17 (50% yield) (eq 10). The results from FVP of 12
and 13 suggest that, under the reaction conditions, carbenes 34
and 36 are interconvertable via a vinylcarbeneꢀcyclopropene
rearrangement and lead to the ring-contraction product 16 and
the ring-opening product 17 (Scheme 5). It is noteworthy that
the ring-opening process is not observed in the FVP of 5,7 the
benzofuran analogue of 12 (Scheme 1). This is probably due
FVP of 18 at 550 °C and ca. 10ꢀ2 Torr gave 2-vinyl-3-furfural
(28) as the sole product in quantitative yield (>95% yield)
(eq 7). FVP of 19 under the same pyrolysis conditions gave
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Scheme 2
Scheme 3
Scheme 4
to the fact that ring-opening of the resulting carbene inter-
mediate 8 would involve an aromaticity breaking of the fused
benzene ring.
Figure 1), the process is initiated by a ring-opening of 34 with
a very low energetic barrier of 4.5 kcal molꢀ1, resulting in the forma-
tion of low-energy intermediate 30 (26.6 and 29.0 kcal molꢀ1
lower than 34). The intermediate 30 has two rotamers 30a and
30b that are separated by the rotational barriers of 6.9 kcal molꢀ1
for 30a f 30b and 9.3 kcal molꢀ1 for 30b f 30a. The following
[1,4]H shift of 30b was found to be the rate-determining step in
the formation of 17; the activation energy of this step was
calculated to be fairly high with a magnitude of 39.3 kcal molꢀ1
.
Once the hydrogen transfer is complete, the dissociation to the
final product 17 and CO takes place spontaneously without an
energetic barrier. The overall reaction from 34 to 17 is a highly
To provide insight into the pyrolysis behavior from an
energetic viewpoint and theoretical basis for the proposed mech-
anism, the density functional theory method at the B3LYP/6-
311++G (3df,2p) level was invoked to calculate the free energy
profile, at 823.15 K and 1.0 ꢁ 10ꢀ5 atm, for the cascade reactions
starting from the carbene 34. The calculated results are presented
in Figure 1.
exergonic process with a free energy change of ꢀ83.2 kcal molꢀ1
.
Considering the cascade reaction leading to the product of
methylenecyclobutenone (16) (progression to the right from 34
in Figure 1), the carbene 34 first undergoes a conversion to the
intermediate of cyclopropene 35, which is about 14.2 kcal molꢀ1
higher in energy than 34. The cyclopropene 35 readily transforms
Regarding the cascade reaction leading to the products,
1-buten-3-yne (17) and CO (progression to the left from 34 in
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Scheme 5
Figure 1. Free energy profile calculated at the CCSD(T)/aug-cc-pVTZ//B3LYP/6-311++G(3df,2p) level of theory. The relative free energies are
given in kcal molꢀ1. The imaginary frequencies and the corresponding vibrational modes are presented for the transition states.
into the carbene 36 with a relatively small activation energy of ca.
7 kcal molꢀ1. The carbenes 34 and 36 are close in energy with the
latter being 5.4 kcal molꢀ1 lower than the former. The subse-
quent ring-contraction process of 36 is characterized by a fairly
high activation energy of 33.3 kcal molꢀ1 and is, thus, the rate-
determining step in the production of 16. The overall reaction
from 34 to 16 is also highly exergonic with a free energy change of
the preference for product 17 by the larger population for
intermediate 30b than for intermediate 36.
The assumption we just made, that is, the intermediates can be
considered in equilibrium, finds support from both theoretical
and experimental results. On the theoretical side, the largest ene-
rgetic barriers for the interconversions 34 T 30 and 34 T 36 are
31.1 kcal molꢀ1 (30a f 34) and 26.7 kcal molꢀ1 (36 f 35),
respectively. These barriers are significantly smaller than the
barriers for the corresponding rate-determining steps of 30b f
17 and 36 f 16, implying that the intermediates have time to
interconvert and reach equilibrium before transformation into
the final products. On the experimental side, the pre-equilibrium
of the intermediates is in agreement with and validated by the
experimental observation that the FVP of 12 and 13 gives the
same distribution of pyrolysis products.
ꢀ40.5 kcal molꢀ1
.
With these computational data in hand, we are now in a
position to rationalize the pyrolysis behavior observed in experi-
ment. The computational results show that the activation energy
for the rate-determining step for 34 f 17 is about 6 kcal molꢀ1
larger than that for 34 f 16, which seems to conflict with the
experimental observation that product 17 has higher yield than
16. However, as can be clearly seen from Figure 1, the transfor-
mation from 34 to 17 proceeds through the formation of low-
lying intermediates (30a and 30b), whereas the intermediates
formed in the process 34 f 16 are relatively high in energy
(35 and 36). Supposing that these intermediates are in equilib-
rium under the experimental conditions, we can thus rationalize
In addition, the reaction of 34 f 17 was found to be more
exergonic than the reaction of 34 f 16, which is consistent with
the observation that the dissociation into the 17 and CO is a
more favorable channel. The low free energy of state 17 + CO is,
in fact, originated from the entropy effect, since it is a dissociation
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process. On the other hand, if we consider the enthalpy change,
34 f 17 (ΔH = ꢀ28.8 kcal molꢀ1) was calculated to be less
exothermic than 34 f 16 (ΔH = ꢀ38.8 kcal molꢀ1). In other
words, the product 16 is more stable than the product 17 + CO in
terms of enthalpy. This result is not surprising if one recognizes
the fact that there are two more carbonꢀcarbon bonds in 16 than
in 17 + CO.
In summary, our experimental and computational results
support the involvement of a vinylcarbeneꢀcyclopropene re-
arrangement in the formation of 16 and 17 from the FVP of 12
and 13 (Scheme 5). Some highly functionalized compounds such
as 16, 17, 29, and 30 were synthesized from the systems under
study. We are currently extending our study to the other hetero-
aromatic systems.
1H), 4.27 (q, J = 6.9 Hz, 2H), 2.92 (q, J = 7.0 Hz, 2H), 1.33 (t, J = 6.9 Hz,
3H), 1.20 (t, J = 7.0 Hz, 3H).
2-Ethyl-3-furoic Acid (21). To a solution of 1.68 g (10 mmol) of
25 in 50 mL of EtOH was added 10 mL of a saturated aqueous solution
of KOH. The mixture was stirred at room temperature for 10 h and then
neutralized with 1 M HCl. The reaction mixture was extracted with ether
(3 ꢁ 20 mL). The ether exatracts were combined and washed with
saturated NaCl (3 ꢁ 20 mL) and dried with MgSO4. After evapovation
of the solvent, 21 was obtained in 90% yield (1.12 g, 9.0 mmol). 21: mp
84ꢀ85 °C; IR (CHCl3, cmꢀ1) 1690 (CdO); 1H NMR (CDCl3) δ 7.02
(d, J = 1.5 Hz, 1H), 6.45 (d, J = 1.5 Hz, 1H), 2.92 (q, J = 7.0 Hz, 2H), 1.21
(t, J = 7.0 Hz, 3H). [Lit.13 mp 84ꢀ85 °C; 1H NMR (CDCl3) δ 7.02 (d,
J = 1.5 Hz, 1H), 6.45 (d, J = 1.5 Hz, 1H), 2.92 (q, J = 7.0 Hz, 2H), 1.21
(t, J = 7.0 Hz, 3H)].
Benzoic 2-Ethyl-3-furoic Anhydride (18). A procedure de-
scribed for the preparation of 12 was followed for the reaction of 2-ethyl-
3-furoic acid with benzoyl chloride to give 90% yield of 18: IR
’ EXPERIMENTAL SECTION
1
(CHCl3, cmꢀ1) 1780 (CdO), 1720 (CdO); H NMR (CDCl3) δ
8.17ꢀ8.10 (m, 2H), 7.68ꢀ7.63 (m, 1H), 7.55ꢀ7.49 (m, 2H), 7.32 (d,
J = 1.8 Hz, 1H), 6.71 (d, J = 1.8 Hz, 1H), 3.08 (q, J = 7.5 Hz, 2H), 1.29 (t,
J = 7.5 Hz, 3H); 13C NMR (CDCl3) δ 167.3 (C), 162.3 (C), 159.0 (C),
141.0 (CH), 134.5 (CH), 130.5 (CH), 128.9 (C), 128.7 (CH), 111.7 (C),
110.5 (CH), 21.4 (CH2),11.8(CH3); HRMS Calcd for C14H12O4:244.0732.
Found: 244.0751. Anal. Calcd for C14H12O4: C, 69.85; H, 4.92. Found: C,
69.61; H, 4.95.
Benzoic 2-Methyl-3-furoic Anhydride (12). Asolutionof1.55g
(11.0 mmol) of benzoyl chloride in 20 mL of ether was added over a
10-min period to a stirred solution of 1.26 g (10 mmol) of 2-methyl-3-
furoic acid (14)8 and 1.68 mL (12.0 mmol) of triethylamine in 50 mL of
ether. The mixture was stirred at room temperature for 10 h, 25 mL of
water was added, and the mixture was stirred for an additional 1 h. The
organic layer was separated, and the aqueous layer was extracted with
ether (3 ꢁ 20 mL). The ether layers were combined and washed with 1 M
HCl (3 ꢁ 30 mL) and saturated NaCl (3 ꢁ 30 mL). After drying
(MgSO4) and evaporation of the solvent, the crude product was purified
by column chromatography on silica gel (5% ethyl acetate in hexanes) to
give 2.14 g (9.30 mmol, 93% yield) of 12: IR (CHCl3, cmꢀ1) 1780
(CdO), 1720 (CdO); 1H NMR (CDCl3) δ 8.18ꢀ7.50 (m, 5H), 7.31
(d, J = 2.1 Hz, 1H), 6.73 (d, J = 2.1 Hz, 1H), 2.66 (s, 3H); 13C NMR
(CDCl3) δ 162.5 (C), 162.3 (C), 159.1 (C), 141.0 (CH), 134.5 (CH),
130.5 (CH), 128.9 (C), 128.8 (CH), 112.7 (C), 110.6 (CH), 14.0
(CH3); HRMS Calcd for C13H10O4: 230.0579. Found: 230.0571. Anal.
Calcd: C, 67.83; H, 4.35. Found: C, 68.06; H, 4.43.
Benzoic 3-Methyl-2-furoic Anhydride (13). A procedure
described for the preparation of 12 was followed for the reaction of
3-methyl-2-furoic acid (15)9 with benzoyl chloride to give 90% yield of
13: IR (CHCl3, cmꢀ1) 1780 (CdO), 1720 (CdO); 1H NMR (CDCl3)
δ 8.17ꢀ8.14 (m, 2H), 7.67ꢀ7.50 (m, 4H), 647 (d, J = 1.8 Hz, 1H), 2.46
(s, J = 7.5 Hz, 3H); 13C NMR (CDCl3) δ 162.2 (C), 154.3 (C), 146.8
(CH), 146.7 (C), 139.2 (C), 135.9 (C), 134.4(CH), 130.6 (CH), 128.8
(CH), 116.0 (CH), 11.9 (CH3). Anal. Calcd for C13H10O4: C, 67.83; H,
4.35. Found: C, 67.81; H, 4.41.
Ethyl 2-Ethyl-3-furoate (25). To a solution of 11.5 g (100 mmol)
of ethyl acetoacetate in 25 mL of THF (dried over LiAlH4), at 0 °C, was
added dropwise 4.8 mL (2.2 equiv) of n-BuLi. After the solution was
stirred at 10 °C for 10 min, 1.52 g (110 mmol) of CH3I was added, and
the resulting mixture was warmed to room temperature and stirred for
another 15 min. The mixture was then neutralized with 1 M HCl and
extracted with ether (3 ꢁ 20 mL). The ether extracts were combined and
concentracted to give crude 24. Without further purification, 25 mL
(300 mmol) of pyridine was added, and the solution was stirred for
5 min. An amount of 15.8 mL (110 mmol) of 2-chloroacetaldehyde
(a 45% aqueous solution) was added to the pyridine solution, and the
resulting mixture was stirred at room temperature for 4 h. After extrac-
tion with ether (3 ꢁ 30 mL), the ether layers were combined and washed
with water (3 ꢁ 30 mL) and saturated NaCl (3 ꢁ 20 mL). After drying
(MgSO4) and evaporation of the solvent, the crude product was purified
by column chromatograohy on silica gel (5% ethyl acetate in hexanes)
to give 10.9 g (65 mmol, 65% yield) of 25: IR (CHCl3, cmꢀ1) 1780
(CdO); 1H NMR (CDCl3) δ 7.00 (d, J = 1.5 Hz, 1H), 6.43 (d, J = 1.5Hz,
Benzoic 2,5-Dimethyl-3-furoic Anhydride (19). A procedure
described for the preparation of 12 was followed for the reaction of 2,5-
dimethyl-3-furoic acid15 with benzoyl chloride to give 91% yield of 19:
1
IR (CHCl3, cmꢀ1) 1770 (CdO), 1715 (C = O); H NMR (CDCl3)
δ 8.18ꢀ8.14 (m, 2H), 7.67ꢀ7.62 (m, 1H), 7.55ꢀ7.48 (m, 2H), 6.28
(s, 1H), 2.60 (s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3) δ 162.4 (C),
161.1 (C), 159.3 (C), 150.8 (C), 134.2 (CH), 130.3 (CH), 128.9 (C),
128.7 (CH), 113.2 (C), 105.9 (CH), 13.9 (CH3), 13.1 (CH3); HRMS
Calcd for C14H12O4:244.0732. Found: 244.0738. Anal. Calcd for C14H12O4:
C, 69.85; H, 4.92. Found: C, 69.65; H, 5.04.
2,5-Dideuterio-3-furoic Acid (27). To a solution of 5.00 g (44.6
mmol) of 3-furoic (26) in 50 mL of D2O was added 10.0 g (92.6 mmol)
of KOH. The solution was heated to reflux for 10 h. After being cooled to
room temperature, the resulting mixture was neutralized with 1 M HCl
and extracted with ether (4 ꢁ 50 mL). The ether extracts were com-
bined, dried (MgSO4), and concentrated to give 4.62 g (41. mmol, 91%
1
yield) of 27: IR (CHCl3, cmꢀ1) 1675 (CdO); H NMR (CDCl3) δ
10.50ꢀ9.50 (br, 1H), 6.78 (s, 1H); 13C NMR (CDCl3) δ 168.6 (C),
149.0 (CD), 144.0 (CD), 118.6 (C), 109.8 (CH); LRMS (m/z, rel
intensity) 114 (M+, 100).
5-Deuterio-2-methyl-3-furoic Acid (23). To a solution of 4.50
g (39.5 mmol) of 27 in 100 mL of THF (dried over LiAlH4) was added
2.2 equiv of n-BuLi in hexanes dropwise at ꢀ78 °C under nitrogen. After
the reaction mixture was stirred at ꢀ78 °C for 30 min, a 3.73 g (26.3 mmol)
quantity of CH3I was added, and the mixture was allowed to warm to
room temperature and stirred for another 3 h. The mixture was then
poured into 100 mL of water. After separation, the aqueous layer was
extracted with ether (3 ꢁ 30 mL), and the combined organic layers were
dried (MgSO4) and evaporated. The crude product was purified by
recrystallization from hexanes to give 3.51 g (27.6 mmol, 72% yield) of
1
23: mp 101ꢀ102 °C; IR (CHCl3, cmꢀ1) 1700 (CdO); H NMR
(CDCl3) δ 12.00ꢀ11.00 (br, 1H), 6.68 (s, 1H), 2.60 (s, 3H); 13C NMR
(CDCl3) δ 170.0 (C), 160.9 (C), 140.6 (CD), 112.9 (C), 110.6 (CH),
13.8 (CH3); LRMS (m/z, rel, intensity) 127 (M+, 100).
Benzoic 5-Deuterio-2-methyl-3-furoic Anhydride (20).
A procedure described for the preparation of 12 was followed for the
reaction of 5-deuterio-2-methyl-3-furoic acid with benzoyl chloride to
give 93% yield of 19: IR (CHCl3, cmꢀ1) 1800 (CdO), 1720 (CdO);
1H NMR (CDCl3) δ8.17ꢀ8.10 (m, 2H), 7.70ꢀ7.60 (m, 1H), 7.55ꢀ7.40
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(m, 2H), 6.70 (s, 1H), 2.65 (s, 3H); 13C NMR (CDCl3) δ 162.3 (C),
162.2 (C), 159.0 (C), 141.0 (CD), 134.4 (CH), 130.4 (CH), 128.8 (C),
128.7 (C), 112.6 (C), 110.3 (CH), 14.0 (CH3); HRMS Calcd for
C13H9O4D: 231.0639. Found: 231.0634.
1H NMR (CDCl3) δ 5.70ꢀ5.40 (m, 2H), 2.82 (s, 1H); 13C NMR
(CDCl3) δ 128.9 (CH2), 82.8 (C), 77.8 (CH).
Computational Methods. Density functional theory method at
the B3LYP/6-311++G(3df,2p) level were applied to optimize the
stationary structures. Vibrational frequency calculations were subsequently
carried out at the same level of theory for two purposes: (i) identification
of the nature of the optimized structures (all positive frequencies for a
minimum and one imaginary frequency for a transition state) and (ii)
thermochemical corrections to obtain enthalpies and free energies. All
transition states were checked to connect the proper minima by intrinsic
reaction coordinates (IRC) calculations. To simulate the experimental
conditions, thermochemical corrections were performed at 823.15 K
and 1.0 ꢁ 10ꢀ5 atm instead of standard conditions. In order to obtain
more accurate energies, single-point calculations using a high-level
correlated coupled cluster method with single, double, and noniterative
triple excitations, CCSD(T), combined with the aug-cc-pVTZ basis set
were performed on the B3LYP/6-311++G(3df,2p) optimized structures.
Our preliminary calculations at the B3LYP/6-311++G(d,p) level indicate
that the singlet state is more stable than the triplet state for carbenes 34
and 36 by 8.7 kcal molꢀ1 and 18.5 kcal molꢀ1, respectively; we therefore
consider only the singlet carbenes in the following computational study
on the reaction mechanism. All calculations were accomplished with the
Gaussian 09 program.20
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 in a Pyrex boat was placed into the sample chamber, and the
system was evacuated to ca. 10ꢀ2 Torr. The sample chamber was heated
to ca. 50 °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 side
arm. 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 pro-
ducts were purified for identification.
Pyrolysis of Benzoic 2-Methyl-3-furoic Anhydride (12). 12
(850 mg, 3.70 mmol) was pyrolyzed at 550 °C and ca. 10ꢀ2 Torr in the
normal manner for 3 h. One milliliter of CDCl3 and a weighed amount of
dibromomethane as an integration standard were added to the product
trap. 1H NMR analysis of this mixture showed the presence of 16
(50.2 mg, 0.630 mmol, 17%) and 17 (106 mg, 2.04 mmol, 55%). 16 and
17 can be separated by low-pressure distillation. 16: 1H NMR (CDCl3)
δ 8.73 (d, J = 2.7 Hz, 1H), 7.08 (d, J = 2.7 Hz, 1H), 5.10 (d, J = 0.9 Hz,
1H), 4.82 (d, J = 0.9 Hz, 1H); 13C NMR (CDCl3) δ 188.6 (C), 172.5
(CH), 157.6 (C), 153.3 (CH), 98.0 (CH2). [Lit.10 16: 1H NMR (CDCl3)
δ 8.66, 7.16, 5.01, 4.78]. 17: 1H NMR (CDCl3) δ 5.80ꢀ5.40 (m, 3H),
2.82 (s, 1H); 13C NMR (CDCl3) δ 128.8 (CH2), 116.3 (CH), 82.2 (C),
’ ASSOCIATED CONTENT
S
Supporting Information. Spectroscopic data for 12, 13,
b
16, 17, 18, 19, 20, 28, 29, 30, 31, and 32, computational details of
16, 17, 30, 34, 35, and 36. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
77.8 (CH). [Lit.17 17: H NMR (CDCl3) δ 5.8ꢀ5.4 (m, 3H), 2.88
(s, 1H); 13C NMR (CDCl3) δ 128.6, 116.4, 82.3, 77.8].
’ AUTHOR INFORMATION
Pyrolysis of Benzoic 3-Methyl-2-furoic Anhydride (13). A
900 mg (3.91 mmol) quantity of 13 was pyrolyzed at 550 °C and ca.
10ꢀ2 Torr in a procedure described for the FVP of 12 to give 45.9 mg
(0.587 mmol, 15%) of 16 and 102 mg (1.96 mmol, 50%) of 17.
Pyrolysis of Benzoic 2-Ethyl-3-furoic Anhydride (18). A 310
mg (1.27 mmol) quantity of 18 was pyrolyzed at 550 °C and ca. 10ꢀ2
Torr in a procedure described for the FVP of 12 to give 28 in 96% yield
(149 mg, 1.27 mmol). 28: IR (CHCl3, cmꢀ1) 1680 (CdO); 1H NMR
(CDCl3) δ 10.05 (s, 1H), 7.37 (d, J = 1.8 Hz, 1H), 7.00 (dd, J = 17.4,
11.4 Hz, 1H), 6.77 (d, J = 1.8 Hz, 1H), 6.07 (dd, J = 17.4, 0.9 Hz, 1H),
5.60 (dd, J = 11.4, 0.9 Hz, 1H); 13C NMR (CDCl3) δ 184.4 (CH), 158.6
(C), 142.8 (CH), 122.7 (C), 122.2 (CH), 119.7 (CH2), 109.1 (CH).
HRMS Calcd for: C7H6O2: 122.0368. Found: 122.0368.
Corresponding Author
*Fax: +886-7-5253909. E-mail: ch-chou@mail.nsysu.edu.tw.
’ ACKNOWLEDGMENT
We thank the National Science Council of the Republic of
China for financial support.
’ REFERENCES
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7.8 Hz, 1H), 5.86 (dd, J = 8.7, 8.4 Hz, 1H), 2.27 (s, 3H); 13C NMR
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NMR (CDCl3) δ 188.6 (C), 157.6 (C), 153.3 (CH), 98.0 (CH2). 32:
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