[4,5]. In 1988, the Diels–Alder reaction of methyl acrylate with cyclopentadiene in scCO2 was firstly reported by Kim and Johnston
[5k]. Subsequently, many Diels–Alder reactions with different substrates, such as the Diels–Alder reaction of isoprene with methyl
acrylate [5g], the regioselective Diels–Alder reaction of methyl acrylate with 2-tert-butyl-1,3-butadiene [5h], and the stereoselective
Diels–Alder reaction of cyclopentadiene with a chiral dienophile [5c], have been investigated in scCO2. However, the Diels–Alder
reaction of CPD with BD in scCO2 to synthesize VNB has not been reported thus far. In the course of our research on the application of
carbon dioxide as a starting material or a solvent [6], we found that the Diels–Alder reaction of CPD with BD can also proceed
effectively in scCO2 without any additional inhibitor to provide VNB in satisfactory yield with high selectivity. The results are
presented in this paper.
2. Results and discussion
In the initial studies conducted, scCO2 and several traditional solvents including THF, hexane, and methanol were investigated at
205 °C. The results are summarized in Table 1 (Table 1, entries 1–5). As shown in Table 1, THI was observed as the main by-product
in the reaction. Interestingly, the reaction could occur under solvent-free conditions (entry 1); the highest conversion of CPD (64%)
was achieved in this case. However, large amounts of unidentified compounds were generated (20% total yield) along with the desired
product VNB (21% yield). A slightly decreased conversion of CPD and an almost similar yield of VNB were observed when the
nonpolar solvent hexane was examined (entry 2: CPD conversion, 59%; VNB yield, 22%). The conversion of CPD and the yields of
VNB, THI, and unidentified compounds were all lower than those observed in hexane when the polar solvents THF and methanol were
investigated (THF: 43% conversion of CPD, 15% and 18% yields of VNB and THI, respectively; methanol: 25% conversion of CPD,
9% and 10% yields of VNB and THI, respectively). These results indicate that a nonpolar solvent is advantageous to the target product.
The scCO2 was finally examined, and the results were shown in entry 5. Up to 47% conversion of CPD and 25% yield of VNB were
observed; the main by-product THI and the unidentified by-products were identified in 17% and 6% total yields, correspondingly.
Although the conversion of CPD was lower than that found in hexane, a relatively high yield and selectivity of VNB were observed
(entry 5, 25% yield and 52% selectivity). Furthermore, the unidentified compounds were generated in relatively low total yield (6%) in
scCO2. However, the conversion of CPD and the yields of VNB, THI, and unidentified compounds all decreased when 4-oxo-2,2,6,6-
tetramethylpiperidinooxy was used as an inhibitor (entry 6, 34% conversion of CPD, 17% and 13% yields of VNB and THI,
respectively). It was considered that the special physical properties of scCO2, such as zero surface tension, large diffusion coefficient,
and analogous solubility with liquids, inhibited the occurrence of side reactions.
After the unique advantage of scCO2 used in the Diels–Alder reaction between CPD and BD as the reaction medium was
demonstrated, some efforts were made to optimize the reaction conditions, including the reaction temperature, reaction time, CO2
density, and BD/CPD molar ratio. The effect of temperature on the reaction is shown in Fig. 1a. The yields of VNB and THI increased
with the elevated temperature, but the influence of the temperature on the yield of THI was more obvious than that on VNB yield. For
example, THI was obtained in only 7% yield at 185 °C, which was lower than half of the yield of VNB (17%). However, almost the
same yield of THI (27%) was observed as the yield of VNB (28%) when the temperature was increased to 215 °C. Notably, the
amounts of unidentified compounds also increased with the enhanced temperature. Similarly, the conversion of CPD increased with the
enhanced temperature. Obviously, the conversion of CPD and the yields of VNB and THI all increased with the enhanced temperature.
Considering the effect of temperature on the conversion of CPD and the yields of VNB and THI, 205 °C was selected as the reaction
temperature.
A series of comparative experiments was conducted to evaluate the influence of reaction time on the conversion and yields, and the
results are summarized in Fig. 1b. When the Diels–Alder reaction between CPD and BD was performed at 205 °C for a prolonged time
(from 30 min to 90 min) in scCO2, both the yield of VNB and the conversion of CPD increased (VNB yield: from 17% to 28%; CPD
conversion: from 26% to 58%). The conversion of CPD increased sharply at the initial 60 min, and then the increase slowed down
from 60 min to 90 min. This finding indicated that the influence of reaction time on the yield of THI was larger than that on the yield
of VNB (VNB yield, from 17% to 28%; THI yield, from 9% to 24%). Moreover, the prolonged reaction time resulted in an increased
amount of unidentified compounds. Relatively good results were obtained when the reaction mixture was treated for 60 min.
The next optimization step involved CO2 density variations, as detailed in Fig. 1c. When the reaction of CPD with BD was
performed at 205 °C for 60 min in the absence of any solvents, the yields of VNB and THI were observed around 20% (VNB yield,
21%; THI yield, 23%). Unidentified compounds were also obtained with 20% total yield under solvent-free conditions. With CO2
density gradually approaching supercritical condition (from 0 g/cm3 to 0.25 g/cm3), the conversion of CPD and the total yield of
unidentified compounds declined obviously (conversion of CPD, from 64% to 46%; total yield of unidentified compounds, from 20%
to 6%); the yield of VNB increased from 21% to 25%, whereas the yield of THI decreased from 23% to 16%. With further increase of
CO2 density from 0.25 g/cm3 to 0.35 g/cm3, the yields of VNB and THI remained unchanged. Meanwhile, the conversion of CPD and
the total yield of unidentified compounds decreased slightly (conversion of CPD, from 46% to 42%; total yield of unidentified
compounds, from 6% to 3%). Therefore, scCO2 with 0.25 g/cm3 density was selected as solvent in subsequent studies.