Diels-Alder reactions between cyclopentadiene analogs and benzoquinone in water and their application in the synthesis of polycyclic cage compounds

Article abstract of DOI:10.1039/c9ra09745g

Diels-Alder reactions between cyclopentadiene analogs and p-benzoquinone were explored in water and yielded 83-97% product, higher than the results reported in water with a catalyst or cetrimonium bromide (CTAB) micelles. The novel adduct 10 was synthesized and further used to synthesize the bi-cage hydrocarbon 4,4′-spirobi[pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane], which has a high density (1.2663 g cm^-3) and a high volumetric heat of combustion (53.353 MJ L^-1). Four novel bi-cage hydrocarbon compounds were synthesized in water using this method starting from 2,2′-bi(p-benzoquinone) and cyclopentadiene analogs.

Full text of DOI:10.1039/c9ra09745g

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Diels–Alder reactions between cyclopentadiene
analogs and benzoquinone in water and their
application in the synthesis of polycyclic cage
compounds†
Cite this: RSC Adv., 2020, 10, 739
ab
a
Xuejing Liu, Ying Han,a Peng Yan,a Fusheng Biea and Han Caoa
*
*
Yijun Shi,
Diels–Alder reactions between cyclopentadiene analogs and p-benzoquinone were explored in water and
yielded 83–97% product, higher than the results reported in water with a catalyst or cetrimonium bromide
(CTAB) micelles. The novel adduct 10 was synthesized and further used to synthesize the bi-cage
Received 21st November 2019
Accepted 16th December 2019
hydrocarbon 4,40-spirobi[pentacyclo[5.4.0.02,6.03,10.05,9]undecane], which has
a
high density
(1.2663 g cmꢀ3) and a high volumetric heat of combustion (53.353 MJ Lꢀ1). Four novel bi-cage
hydrocarbon compounds were synthesized in water using this method starting from 2,20-bi(p-
benzoquinone) and cyclopentadiene analogs.
DOI: 10.1039/c9ra09745g
rsc.li/rsc-advances
a catalyst or CTAB micelles, but the yield was 67%, which was
lower than in toluene (entry 3).60 Apart from these, the other
Introduction
Diels–Alder reactions shown in Table 1 were done in organic
solvents, and their yields were 76–97%.54,56,61–63
In recent years, water has been reported as a desirable solvent
for many chemical reactions for reasons of cost, safety, and
environmental concerns. Most notably, the Diels–Alder reaction
has been found to be accelerated in dilute aqueous solution,
and it is undoubtedly one of the most important reactions in the
synthesis of polycyclic cage compounds.1–5 Polycyclic cage
compounds have drawn more and more attention in the elds
of medicinal chemistry and high energy density materials.6–56
The Diels–Alder reaction was developed by Diels and Alder in
1928 and the product of this reaction between cyclopentadiene
and p-benzoquinone57 was further applied in the preparation of
pentacyclo[5.4.0.02,6.03,10.05,9]undecane (PCUD) by Marchand53
(Scheme 1).
In this paper, Diels–Alder reactions between cyclopentadiene
analogs and p-benzoquinone were further explored in water to
improve the adduct yields. The new structure of adduct 10 is
reported and used to synthesize the bi-cage hydrocarbon 4,40-
spirobi[pentacyclo[5.4.0.02,6.03,10.05,9]undecane], which has
a high density (1.2663 g cmꢀ3) and a high volumetric heat of
combustion (53.353 MJ Lꢀ1).56 Furthermore, new polycyclic bi-
cage scaffolds were synthesized in water using this method
starting from 2,20-bi(p-benzoquinone) and cyclopentadiene
analogs (1 and 2).
So far, several Diels–Alder reactions between cyclo-
pentadiene analogs and p-benzoquinone have been carried out
Results and discussion
in water (Table 1) and the Diels–Alder adducts (Scheme 2) have In order to improve the yields of Diels–Alder reactions between
been further applied in the synthesis of polycyclic cage cyclopentadiene analogs and p-benzoquinone in water, the
compounds, but this required the addition of an organo- reaction between cyclopentadiene and p-benzoquinone at room
tungsten Lewis acid as a catalyst (entry 1)58 or cetrimonium temperature in water was chosen as the model reaction. We
bromide (CTAB) micelles (entry 2)59 and yielded lower than in found that dissolving p-benzoquinone into cyclopentadiene was
organic solvents. Only the Diels–Alder reaction between 1,3- an instantly exothermic process, and the state of this reaction
cyclohexadiene and p-benzoquinone was done in water without changed to solid from liquid along with a decrease in
temperature.
aEngineering and Technology Research Institute of Lunan Coal Chemical, Zaozhuang
University, Beian Road, Zaozhuang 277160, Shandong Province, China. E-mail:
673230386@qq.com
bCollege of Chemistry, Chemical Engineering and Materials Science, Zaozhuang
University, Beian Road, Zaozhuang 277160, Shandong Province, China
† Electronic supplementary information (ESI) available. CCDC 1936540, 1936541
and 1936543. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c9ra09745g
Scheme 1 Synthesis of PCUD.
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Table 1 The reported Diels–Alder reactions between cyclopentadiene analogs and p-benzoquinone
Entry
Diene
Solvent
Conditions
Time/h
Yield/%
1
2
3
4
1
2
3
4
CH2Cl2
Water
Benzene
Water
Toluene
Water
MeOH
0–25 ꢁC, organotungsten Lewis acid, rt
Reux, CTAB micelles, rt
Reux, rt
2.25
2
15
3
24
48
5
94–97
87
82
66
76
67
76
ꢀ10–25 ꢁ
C
Based on this phenomenon and the solubility of p-benzo-
Further investigation was carried out to study the synthesis
quinone in water, different methods of dropping were explored of a bi-cage hydrocarbon from adduct 10. Finally, the polycyclic
(Fig. 1). When water was added to p-benzoquinone (a), only cage hydrocarbon compound 12, which was important in the
a small amount of p-benzoquinone was dissolved in water (b). synthesis of 4,40-spirobi[pentacyclo[5.4.0.02,6.03,10.05,9]unde-
The system presented three phases because of the different cane], was synthesized by intramolecular [2 + 2] photo-
densities aer cyclopentadiene was added (c), and a large cyclization and Wolff–Kishner reduction from 10 (Scheme 3).
amount of p-benzoquinone was unreacted with cyclopentadiene
aer 24 h (d).
To expand the scope of this method in water, we found that
the structure of 2,20-bi(p-benzoquinone) was similar to that of p-
When cyclopentadiene was added to p-benzoquinone (A), the benzoquinone and can be synthesized by oxidation of 2,20-
state of this reaction changed to liquid from solid along with an biphenol.64 According to the structure of 2,20-bi(p-benzoqui-
increase in temperature. The system presented two liquid none) and the high reactivity of p-benzoquinone with cyclo-
phases aer water was added (C), and almost all of the product pentadiene, inspiration was drawn and a convenient synthetic
(6) had precipitated aer 2 h. The product was simply obtained strategy to construct two cages simultaneously in the synthesis
in 96% yield by ltration and recrystallization. Compared with of bi-cage hydrocarbon compounds was designed (Scheme 4). In
the reaction in Table 1, this reaction was done in water without this scheme, the Diels–Alder reaction in water was applied and
a catalyst and the yield was improved from 87% to 96%. bi-cage hydrocarbon compounds HV-1 and HV-2 were
Compared with the method of dropping in Fig. 1a and b, the synthesized.
method of dropping in Fig. 1A and B yielded more because it
reacted more fully in two phases.
Following Scheme 4, two isomers (D-A-1 : D-A-2 ¼ 32 : 28) were
obtained by the Diels–Alder reaction of 2,20-bi(p-benzoquinone)
Based on the method shown in Fig. 1A–D, the results of Diels– with cyclopentadiene with an overall yield of 60% and separated.
Alder reactions between cyclopentadiene analogs and p-benzo- The intramolecular [2 + 2] photocyclization of D-A-1 at room
quinone in water are shown in Table 2. The yields (90–97%, temperature with a medium-pressure mercury immersion lamp
entries 1–4) were higher than those reported previously and the formed HV-1 in 90% yield and HV-2 was obtained in 87% yield by
novel product 10 was synthesized in 83% yield. Products 6–9 have the intramolecular [2 + 2] photocyclization of D-A-2.
been reported to be important in the synthesis of polycyclic cage
To conrm the structures of the bi-cage hydrocarbon
hydrocarbons, such as PCUD and bi-cage hydrocarbon 4,40-spi- compounds HV-1 and HV-2, crystals of compounds HV-1 and
robi[pentacyclo[5.4.0.02,6.03,10.05,9]undecane].
Scheme 2 Diels–Alder reactions between cyclopentadiene analogs Fig. 1 Diels–Alder reactions between cyclopentadiene and p-ben-
and p-benzoquinone.
zoquinone (1 : 1) in water.
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Table 2 Diels–Alder reactions between cyclopentadiene analogs and
p-benzoquinone in watera
Entry
Diene
Solvent
Time/h
Product
Yieldb/%
1
2
3
4
5
1
2
3
4
5
Water
Water
Water
Water
Water
2
4
4
4
4
6
7
8
9
96
90
97
91
83
10
Scheme 5 Synthesis of bi-cage hydrocarbon compounds HV-3 and
HV-4.
a
Reaction conditions: n(diene) : n(p-benzoquinone)
¼
1 : 1, n(p-
b
benzoquinone) ¼ 4.63 mmol, V(water, pH ¼ 7) ¼ 5 mL, rt. Isolated
yield.
Scheme 3 Synthesis of 12 from 10.
Fig. 3 X-ray crystal structure of HV-4 (CCDC 1936543).
To conrm the structures of the bi-cage hydrocarbon
compounds HV-3 and HV-4, only a crystal of compound HV-4
suitable for X-ray diffraction was obtained by recrystallization.
The crystal structure of compound HV-4 (Fig. 3) is very similar to
the structure of compound HV-2 and the two cyclopropyl
structures share two spiro-carbons with the bi-cage structures.
Scheme 4 Synthesis of bi-cage hydrocarbon compounds HV-1 and
HV-2.
Conclusions
In summary, the Diels–Alder reactions between cyclopentadiene
analogs and p-benzoquinone were done in water used the
method of dropping shown in Fig. 1A and B and yielded more
than previously reported in water with a catalyst or CTAB
micelles. The novel adduct 10 was synthesized and further used
to synthesize the bi-cage hydrocarbon 4,40- spirobi[pentacyclo
[5.4.0.02,6.03,10.05,9]undecane]. Furthermore, four bi-cage
hydrocarbon compounds were synthesized in water using this
method starting from 2,20-bi(p-benzoquinone) and cyclo-
pentadiene analogs (1 and 2). Additionally, further work on the
synthesis of more polycyclic cage (one cage or two cages)
compounds is underway in our laboratory.
HV-2 suitable for X-ray diffraction were obtained by recrystalli-
zation. In the crystal structures of compounds HV-1 and HV-2
(Fig. 2), two polycyclic cages were clearly connected with a single
C–C bond, which directly conrmed the bi-cage structures.
Based on Scheme 4, bi-cage hydrocarbon compounds HV-3
and HV-4 were synthesized as shown in Scheme 5. Two isomers
(D-A-3 : D-A-4 ¼ 38 : 34) were obtained by the Diels–Alder reac-
tion of 2,20-bi(p-benzoquinone) with 2 with an overall yield of
72% and separated. The intramolecular [2 + 2] photocyclization
of D-A-3 at room temperature with a medium-pressure mercury
immersion lamp formed HV-3 in 88% yield and HV-4 was ob-
tained in 80% yield by the intramolecular [2 + 2] photocyclization
of D-A-4.
Experimental
General procedures
All chemicals were purchased from commercial sources and
used without further purication. Melting points were
measured using an INESA (SGWX-4B) melting point detector
and are uncorrected. NMR spectra were recorded with Bruker
Avance 400M or Bruker Avance 500M spectrometers. MS data
were recorded with a Micromass-GC/TOF mass spectrometer
GCT (UK) and a Thermo-LTQ ORBITRAP XL. IR data were
recorded with a NICOLET 6700 FT-IR. The X-ray single-crystal
diffraction analysis was performed on an Agilent Supernova
CCD diffractometer instrument.
Fig. 2 X-ray crystal structures of HV-1 (CCDC 1936540) and HV-2
(CCDC 1936541).
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4 h. The precipitate was ltered and recrystallized from n-
hexane to yield 8 (0.84 g, 4.47 mmol, 97%) as yellow needles.
Mp: 88–90 ꢁC. IR (lm): 2947, 2866, 1662, 1611, 1289, 1277,
1257, 1176, 1163, 1107, 1044, 1018, 877, 798, 722, 710 cmꢀ1. 1H
NMR (400 MHz, CDCl3) d 6.63 (s, 2H), 6.29–6.11 (m, 2H), 3.20 (d,
J ¼ 1.1 Hz, 2H), 2.98 (s, 2H), 1.80–1.60 (m, 2H), 1.47–1.17 (m,
2H). 13C NMR (101 MHz, CDCl3) d 198.36 (C), 140.98 (CH),
132.45 (CH), 48.32 (CH), 34.32 (CH), 23.72 (CH2).
Synthesis and analytical data for 2
2 was prepared by the procedure described by Marchand.54 1H
NMR (400 MHz, CDCl3) d 6.59–6.49 (m, 2H), 6.19–6.10 (m, 2H),
1.66 (s, 4H).
Synthesis and analytical data for 4
4 was prepared by the procedure described by Semmelhack.65
1H NMR (500 MHz, CDCl3) d 6.86–6.78 (m, 1H), 6.30–6.27 (m,
1H), 6.21–6.14 (m, 1H), 6.08–5.99 (m, 1H), 4.88–4.81 (m, 2H),
2.12–2.03 (m, 2H), 1.77–1.72 (m, 2H), 1.60 (s, 3H), 1.34 (s, 3H).
Synthesis and analytical data for 9
9 was prepared with the same procedure as 6 starting with p-
benzoquinone (0.50 g, 4.63 mmol), 4 (0.89 g, 4.63 mmol) and
water (5 mL). The mixture was stirred at room temperature for
4 h. The precipitate was ltered and recrystallized from n-
hexane to yield 9 (1.26 g, 4.20 mmol, 91%) as yellow needles.
Synthesis and analytical data for 5
5 was prepared by the procedure described by Semmelhack.65
1H NMR (400 MHz, CDCl3) d 6.39–6.35 (m, 1H), 6.25–6.20 (m,
1H), 6.20–6.13 (m, 2H), 4.29 (t, J ¼ 4.4 Hz, 2H), 3.67 (s, 1H), 3.60
(s, 1H), 1.99–1.94 (m, 4H).
ꢁ
Mp: 158–160 C. IR (lm): 2974, 2943, 2908, 1666, 1604, 1384,
1372, 1283, 1208, 1119, 1052, 1022, 988, 877, 843, 728 cmꢀ1. 1H
NMR (400 MHz, CDCl3) d 6.57 (s, 2H), 6.04 (ddd, J ¼ 30.2, 5.7,
2.8 Hz, 2H), 4.57 (dt, J ¼ 32.1, 6.0 Hz, 2H), 3.67 (s, 1H), 3.43 (dd, J
¼ 8.4, 4.2 Hz, 1H), 3.17 (dd, J ¼ 8.4, 4.0 Hz, 1H), 2.96 (s, 1H), 2.03
(dd, J ¼ 14.9, 1.9 Hz, 1H), 1.75 (dd, J ¼ 14.6, 1.6 Hz, 1H), 1.62–
1.47 (m, 5H), 1.26 (s, 3H). 13C NMR (101 MHz, CDCl3) d 199.43
(C), 199.23 (C), 142.58 (CH), 141.97 (CH), 136.89 (CH), 134.37
(CH), 109.33 (C), 80.54 (CH), 79.65 (CH), 68.18 (C), 57.42 (CH2),
53.66 (CH2), 47.99 (CH), 47.69 (CH), 37.77 (CH), 36.68 (CH),
26.36 (CH3), 23.52 (CH3).
Synthesis and analytical data for 2,20-bi(p-benzoquinone)
2,20-bi(p-benzoquinone) was prepared by the procedure
described by Bouaziz.64 1H NMR (400 MHz, CDCl3) d 6.85 (d, J ¼
15.8 Hz, 6H).
Synthesis and analytical data for 6
0.50 g (4.63 mmol) of p-benzoquinone and 0.31 g (4.70 mmol) of
cyclopentadiene were added sequentially to a 25 mL ask
equipped with a magnetic stirrer bar. Water (5 mL) was added
and the mixture was stirred at room temperature for 2 h. The
precipitate was ltered and recrystallized from n-hexane to yield
6 (0.77 g, 4.42 mmol, 96%) as yellow needles. Mp: 76–77 ꢁC. IR
(lm): 2986, 2950, 2926, 1659, 1604, 1298, 1280, 1141, 1066, 915,
Synthesis and analytical data for 10
10 was prepared with the same procedure as 6 starting with p-
benzoquinone (0.50 g, 4.63 mmol), 5 (0.71 g, 4.67 mmol) and
water (5 mL). The mixture was stirred at room temperature for
4 h. The precipitate was ltered and subjected to chromatog-
raphy on silica gel to give 10 (1.00 g, 3.84 mmol, 83%) as yellow
needles. Mp: 160–162 ꢁC. IR (lm): 3348, 2968, 1712, 1659, 1325,
1124, 1075, 956 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 6.58 (s, 2H),
6.04 (dd, J ¼ 9.3, 2.0 Hz, 2H), 4.04 (d, J ¼ 35.0 Hz, 2H), 3.36 (s,
1H), 3.27 (ddd, J ¼ 18.1, 8.3, 3.9 Hz, 2H), 3.11 (s, 1H), 2.40 (s,
1H), 2.27 (s, 1H), 1.85–1.60 (m, 4H). 13C NMR (101 MHz, CDCl3)
d 199.40 (C), 199.26 (C), 142.45 (CH), 142.24 (CH), 136.18 (CH),
135.59 (CH), 73.62 (CH), 72.86 (CH), 64.22 (C), 57.75 (CH2),
56.80 (CH2), 48.18 (CH), 47.99 (CH), 37.08 (CH), 36.76 (CH).
HRMS (EI): C15H16O4 [M]+ calcd, 260.1049; found, 260.1054.
1
872, 852, 725, 709 cmꢀ1. H NMR (400 MHz, CDCl3) d 6.55 (s,
2H), 6.05 (d, J ¼ 1.3 Hz, 2H), 3.53 (d, J ¼ 1.1 Hz, 2H), 3.20 (d, J ¼
1.2 Hz, 2H), 1.52 (dd, J ¼ 8.7, 1.4 Hz, 1H), 1.41 (d, J ¼ 8.7 Hz,
1H). 13C NMR (101 MHz, CDCl3) d 199.46 (C), 142.06 (CH),
135.30 (CH), 48.77 (CH), 48.71 (CH), 48.34 (CH2).
Synthesis and analytical data for 7
7 was prepared with the same procedure as 6 starting with p-
benzoquinone (0.50 g, 4.63 mmol), 2 (0.44 g, 4.78 mmol) and
water (5 mL). The mixture was stirred at room temperature for
4 h. The precipitate was ltered and recrystallized from n-
hexane to yield 7 (0.83 g, 4.15 mmol, 90%) as yellow needles.
Synthesis and analytical data for 11
ꢁ
Mp: 100–102 C. IR (lm): 2980, 1662, 1606, 1301, 1282, 1131,
A solution of 10 (1.00 g, 3.84 mmol) in EtOAc (200 mL) was
irradiated with a 400 W medium-pressure mercury immersion
lamp for 3 h. The reaction mixture was concentrated in vacuo,
and the residue was subjected to chromatography on silica gel
to give 11 (0.90 g, 3.46 mmol, 90%) as a white solid. Mp: 200–
1028, 956, 929, 897, 874, 848, 734 cmꢀ1 1H NMR (400 MHz,
.
CDCl3) d 6.58 (s, 2H), 6.14 (d, J ¼ 1.6 Hz, 2H), 3.38 (d, J ¼ 1.4 Hz,
2H), 2.89 (s, 2H), 0.60 (dd, J ¼ 9.3, 5.7 Hz, 2H), 0.49 (dd, J ¼ 9.5,
5.9 Hz, 2H). 13C NMR (101 MHz, CDCl3) d 199.31 (C), 142.32
(CH), 135.34 (CH), 53.66 (C), 49.21 (CH), 44.56 (CH), 7.96 (CH2),
6.94 (CH2).
202 ꢁC. IR (lm): 3343, 2952, 2925, 1732, 1194, 1076, 1049 cmꢀ1
.
1H NMR (400 MHz, DMSO) d 4.40 (s, 2H), 3.85 (s, 2H), 3.17 (s,
2H), 2.74 (s, 4H), 2.53 (d, J ¼ 38.4 Hz, 2H), 1.78–1.43 (m, 4H). 13
C
Synthesis and analytical data for 8
NMR (101 MHz, DMSO) d 213.19 (C), 73.12 (CH), 73.02 (CH),
8 was prepared with the same procedure as 6 starting with p- 59.80 (C), 54.50 (CH2), 54.46 (CH2), 54.43 (CH), 53.33 (CH), 43.90
benzoquinone (0.50 g, 4.63 mmol), 3 (0.38 g, 4.75 mmol) and (CH), 43.87 (CH), 38.39 (CH), 38.34 (CH), 37.41 (CH), 33.64 (CH).
water (5 mL). The mixture was stirred at room temperature for HRMS (EI): C15H16O4 [M]+ calcd, 260.1049; found, 260.1057.
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(C), 210.54 (C), 55.17 (C), 55.08 (CH), 52.36 (CH), 46.26 (CH),
44.72 (CH), 44.14 (CH), 42.50 (CH), 40.88 (CH), 37.47 (CH2).
HRMS (EI): C22H18O4 [M]+ calcd, 346.1205; found, 346.1212.
Synthesis and analytical data for 12
A solution of 11 (1.00 g, 3.84 mmol) and hydrazine monohydrate
(3.3 mL, 80%, 54.31 mmol) in diethylene glycol (3 mL) was
heated at 135 ꢁC for 20 h and the solution was distilled until the
temperature of the distillate reached 190 ꢁC. Solid potassium
hydroxide (1.51 g, 26.96 mmol) was added portionwise and the
solution was heated at 200 ꢁC for 20 h, allowed to cool, and
diluted with water (50 mL). The precipitate was ltered and
recrystallized from EtOAc to yield 12 (0.55 g, 2.37 mmol, 62%) as
a white solid. Mp: 156–158 ꢁC. IR (lm): 3266, 2933, 2857, 1088,
Synthesis and analytical data for HV-2
A solution of D-A-2 (0.46 g, 1.33 mmol) in EtOAc (30 mL) was
irradiated with a 400 W medium-pressure mercury immersion
lamp for 2 h. The reaction mixture was concentrated in vacuum,
and the residue was subjected to chromatography on silica gel
to give HV-2 (0.40 g, 1.16 mmol, 87%) as white solid. Mp: 306–
1
309 C. IR (lm): 2991, 2935 1742, 1718, 1223, 1083 cmꢀ1. H
1031 cmꢀ1
.
1H NMR (400 MHz, DMSO) d 4.18 (dd, J ¼ 11.7,
ꢁ
NMR (400 MHz, CD2Cl2) d 3.22–3.04 (m, 2H), 3.03–2.73 (m, 6H),
2.62 (s, 4H), 2.40 (s, 2H), 1.96 (d, J ¼ 11.2 Hz, 2H), 1.82 (d, J ¼
11.2 Hz, 2H). 13C NMR (101 MHz, CDCl3) d 210.66 (C), 209.57
(C), 54.00 (C), 53.73 (CH), 50.81 (CH), 45.69 (CH), 43.23 (CH),
42.85 (CH), 40.56 (CH), 39.85 (CH), 36.54 (CH2). HRMS (EI):
4.2 Hz, 2H), 3.85–3.68 (m, 2H), 2.50 (d, J ¼ 30.5 Hz, 4H), 2.28 (s,
2H), 1.88–1.60 (m, 4H), 1.47–1.26 (m, 4H), 0.86 (d, J ¼ 11.9 Hz,
2H). 13C NMR (101 MHz, DMSO) d 73.34 (CH), 73.26 (CH), 57.17
(CH2), 56.11 (CH2), 51.80 (C), 43.12 (CH), 42.97 (CH), 41.33 (CH),
41.16 (CH), 38.58 (CH), 37.48 (CH), 35.39 (CH), 35.35 (CH), 27.14
(CH2), 27.06 (CH2).
C
22H18O4 [M]+ calcd, 346.1205; found, 346.1206.
Synthesis and analytical data for D-A-3 and D-A-4
Synthesis and analytical data for D-A-1 and D-A-2
D-A-3 and D-A-4 were prepared with the same procedure as D-A-
1 and D-A-2 starting with 2,20-bi(p-benzoquinone) (0.50 g, 2.34
mmol), 2 (0.44 g, 4.78 mmol) and water (5 mL). The mixture was
stirred at room temperature for 4 h. The precipitate was ltered
and subjected to chromatography on silica gel to give D-A-3
(0.35 g, 0.88 mmol, 38%) as a yellow microcrystalline solid and
D-A-4 (0.32 g, 0.80 mmol, 34%) as a yellow microcrystalline
solid.
D-A-3. Mp: 163–165 ꢁC. IR (lm): 2997, 1663, 1602, 1245,
1227, 1029, 910, 730 cmꢀ1. 1H NMR (400 MHz, CDCl3) d 6.48 (s,
2H), 6.33–6.23 (m, 2H), 6.19–6.08 (m, 2H), 3.48 (ddd, J ¼ 19.9,
8.5, 3.8 Hz, 4H), 2.90 (s, 4H), 0.66–0.56 (m, 4H), 0.55–0.44 (m,
4H). 13C NMR (101 MHz, CDCl3) d 197.30 (C), 195.70 (C), 147.51
(C), 139.14 (CH), 134.92 (CH), 134.18 (CH), 52.66 (CH), 52.57
(CH), 49.37 (CH), 48.94 (CH), 43.71 (C), 6.97 (CH2), 5.94 (CH2).
HRMS (ESI): C26H22O4 [M + Na]+ calcd, 421.14103; found,
421.14098.
D-A-4. Mp: 156–158 ꢁC. IR (lm): 2977, 1668, 1223, 1198,
1016, 930, 904, 766, 742, 729 cmꢀ1. 1H NMR (400 MHz, CDCl3)
d 6.48 (s, 2H), 6.33–6.27 (m, 2H), 6.20–6.15 (m, 2H), 3.56–3.42
(m, 4H), 2.97–2.79 (m, 4H), 0.69–0.56 (m, 4H), 0.54–0.43 (m,
4H). 13C NMR (101 MHz, CDCl3) d 198.36 (C), 196.86 (C), 148.78
(C), 140.03 (CH), 136.02 (CH), 135.24 (CH), 53.57 (CH), 53.47
(CH), 50.46 (CH), 50.01 (CH), 44.70 (C), 7.98 (CH2), 6.99 (CH2).
HRMS (ESI): C26H22O4 [M + Na]+ calcd, 421.14103; found,
421.14130.
0.50 g (2.34 mmol) 2,20-bi(p-benzoquinone) and 0.31 g (4.70
mmol) cyclopentadiene were added one aer another to a 25 mL
ask equipped with a magnetic stirrer bar. Water (5 mL) was
added and the mixture was stirred at room temperature for 4 h.
The precipitate was ltered and subjected to chromatography
on silica gel to give D-A-1 (0.26 g, 0.75 mmol, 32%) as a yellow
microcrystalline solid and D-A-2 (0.23 g, 0.66 mmol, 28%) as
a yellow microcrystalline solid.
D-A-1. Mp: 162–164 ꢁC. IR (lm): 2984, 2958, 1671, 1658,
1
1197, 1091, 1044, 903, 800, 734, 718 cmꢀ1. H NMR (400 MHz,
CDCl3) d 6.43 (s, 2H), 6.21 (dd, J ¼ 5.4, 2.9 Hz, 2H), 6.05 (dd, J ¼
5.5, 2.9 Hz, 2H), 3.52 (s, 4H), 3.37–3.23 (m, 4H), 1.58–1.52 (m,
2H), 1.43 (d, J ¼ 8.8 Hz, 2H). 13C NMR (101 MHz, CDCl3) d 197.47
(C), 195.86 (C), 147.25 (C), 138.91 (CH), 134.87 (CH), 134.07
(CH), 48.48 (CH), 48.09 (CH), 47.85 (CH), 47.75 (CH). HRMS
(ESI): C22H18O4 [M + Na]+ calcd, 369.11028; found, 369.10995.
D-A-2. Mp: 158–160 ꢁC. IR (lm): 2985, 2962, 2932, 1665,
1605, 1322, 1246, 1194, 1052, 843, 748, 730, 719 cmꢀ1. 1H NMR
(400 MHz, CDCl3) d 6.44 (s, 2H), 6.25–6.17 (m, 2H), 6.07 (dd, J ¼
5.2, 2.3 Hz, 2H), 3.52 (s, 4H), 3.31 (ddd, J ¼ 23.3, 8.9, 3.8 Hz, 4H),
1.55 (d, J ¼ 8.8 Hz, 2H), 1.43 (d, J ¼ 8.7 Hz, 2H). 13C NMR (101
MHz, CDCl3) d 197.47 (C), 195.98 (C), 147.45 (C), 138.76 (CH),
134.93 (CH), 134.14 (CH), 48.55 (CH), 48.13 (CH), 47.78 (CH),
47.64 (CH), 47.54 (CH2). HRMS (ESI): C22H18O4 [M + Na]+ calcd,
369.11028; found, 369.10960.
Synthesis and analytical data for HV-1
Synthesis and analytical data for HV-3
A solution of D-A-1 (0.51 g, 1.47 mmol) in EtOAc (30 mL) was HV-3 was prepared with same procedure as HV-1 and yielded in
irradiated with a 400 W medium-pressure mercury immersion 88% as white solid. Mp: 260–262 ꢁC. IR (lm): 2985, 1734, 1182,
lamp for 2 h. The reaction mixture was concentrated in vacuum, 1080, 1048, 956, 942, 922, 876 cmꢀ1. 1H NMR (400 MHz, CDCl3)
and the residue was subjected to chromatography on silica gel d 3.31 (dd, J ¼ 13.9, 6.2 Hz, 2H), 3.19–3.05 (m, 2H), 2.93 (s, 4H),
to give HV-1 (0.46 g, 1.33 mmol, 90%) as a white solid. Mp: 310– 2.79 (d, J ¼ 6.2 Hz, 2H), 2.38 (s, 2H), 2.32–2.23 (m, 2H), 0.77–0.56
1
313 C. IR (lm): 2962, 2944, 1742, 1731, 1079, 1042 cmꢀ1. H (m, 8H). 13C NMR (101 MHz, CDCl3) d 211.87 (C), 210.52 (C),
ꢁ
NMR (400 MHz, CDCl3) d 3.15 (d, J ¼ 6.2 Hz, 2H), 2.99 (d, J ¼ 55.63 (CH), 55.56 (CH), 53.11 (CH), 50.34 (CH), 49.68 (CH), 46.95
28.5 Hz, 6H), 2.71 (d, J ¼ 11.6 Hz, 6H), 2.03 (d, J ¼ 11.3 Hz, 2H), (C), 42.72 (C), 37.70 (CH), 37.50 (CH), 5.50 (CH2), 4.05 (CH2).
1.89 (d, J ¼ 11.3 Hz, 2H). 13C NMR (101 MHz, CDCl3) d 211.85 HRMS (EI): C26H22O4 [M]+ calcd, 398.1518; found, 398.1527.
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Paper
18 J. Joubert, W. J. Geldenhuys, C. J. Van der Schyf, D. W. Oliver,
H. G. Kruger, T. Govender and S. F. Malan, ChemMedChem,
2012, 7, 375.
19 J. A. Lockman, W. J. Geldenhuys, M. R. Jones-Higgins,
J. D. Patrick, D. D. Allen and C. Van der Schyf, Brain Res.,
2012, 1489, 133.
20 A. S. Sklyarova, V. N. Rodionov, C. G. Parsons, G. Quack,
P. R. Schreiner and A. A. Fokin, Med. Chem. Res., 2013, 22,
360.
21 J. Joubert, R. Sharma, M. Onani and S. F. Malan, Tetrahedron
Lett., 2013, 54, 6923.
Synthesis and analytical data for HV-4
HV-4 was prepared with the same procedure as HV-1 and yiel-
ded 80% as a white solid. Mp: 318–320 ꢁC. IR (lm): 3003, 2985,
2962, 1727, 1221, 1181, 1083, 974, 955, 942, 761 cmꢀ1. 1H NMR
(400 MHz, CDCl3) d 3.48–3.34 (m, 2H), 3.24 (s, 2H), 3.00–2.85
(m, 4H), 2.43 (s, 2H), 2.29–2.15 (m, 4H), 0.77–0.56 (m, 8H). 13
C
NMR (101 MHz, CDCl3) d 210.65 (C), 209.48 (C), 54.48 (CH),
54.18 (CH), 51.50 (CH), 48.86 (CH), 48.45 (CH), 46.36 (C), 40.77
(C), 36.77 (CH), 36.52 (CH), 4.43 (CH2), 3.06 (CH2). HRMS (EI):
C
26H22O4 [M]+ calcd, 398.1518; found, 398.1522.
22 C. Beinat, S. D. Banister, J. Hoban, J. Tsanaktsidis,
A. Metaxas, A. D. Windhorst and M. Kassiou, Bioorg. Med.
Chem. Lett., 2014, 24, 828.
Conflicts of interest
23 J. Joubert, H. Samsodien, Q. R. Baber, D. L. Cruickshank,
M. R. Caira and S. F. Malan, J. Chem. Crystallogr., 2014, 44,
194.
There are no conicts to declare.
24 S. M. Wilkinson, H. Gunosewoyo, M. L. Barron, A. Boucher,
M. McDonnell, P. Turner, D. E. Morrison, M. R. Bennett,
I. S. McGregor, L. M. Rendina and M. Kassiou, ACS Chem.
Neurosci., 2014, 5, 335.
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