A detailed investigation into the one-pot cascade reaction of ethyl 3,9-dimethyl-7-phenyl-6H-dibenzo-[b,d]pyran-6-one-8-carboxylate with phenylhydrazine

Article abstract of DOI:10.1007/s11164-020-04192-x

Abstract: When synthesizing cyclohexane-annulated pyrazolones from a cyclohexonedicarboxylate derivative with phenylhydrazine under the catalysis of sulfuric acid in the air, up to five products were finally obtained from the one-pot procedure. Among the

Full text of DOI:10.1007/s11164-020-04192-x

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04192-x
A detailed investigation into the one‑pot cascade
reaction of ethyl 3,9‑dimethyl‑7‑phenyl‑6H‑dibenzo‑[b,d]
pyran‑6‑one‑8‑carboxylate with phenylhydrazine
Chao‑Yue Chen1 · Yu Qiao1 · Lei Zhang1 · Xin Wang1 · Ting‑Hai Yang1,2
Received: 21 November 2019 / Accepted: 14 June 2020
© Springer Nature B.V. 2020
Abstract
When synthesizing cyclohexane-annulated pyrazolones from a cyclohexonedicar-
boxylate derivative with phenylhydrazine under the catalysis of sulfuric acid in the
air, up to fve products were fnally obtained from the one-pot procedure. Among
the obtained fve products derived from the reaction, two unexpected products were
identifed, an interesting cyclohexane-annulated pyrazolone bearing a hydroperox-
ide group and a cyclohexene-annulated pyrazolone, both by crystallographic analy-
sis. Reaction optimization and product distributions were investigated in diferent
reaction conditions. A reaction mechanism for the formation of the fve products
has been proposed, and the two unexpected pyrazolones were suggested to be from
the three-step cascade products of the condensation/amidation/peroxidation and the
condensation/amidation/dehydration, respectively.
Graphic abstract
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04192-x) contains supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
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C.-Y. Chen et al.
Keywords Pyrazolone · Cascade reaction · Cyclohexonedicarboxylate · Synthesis ·
Crystallographic analysis
Introduction
Pyrazolone derivatives are an essential class of nitrogen-containing heterocycle
compounds that possess many applications in pharmaceutical chemistry [1], coor-
dination chemistry [2], and functional materials [3]. More importantly, as one of
the most frequently encountered pharmacophores, pyrazolones exhibit a broad
range spectrum of pharmacological and biological activities, such as analgesic [4],
anti-infammatory [5], antitumor [6], antimicrobial [7], hypoglycemic [8], and anti-
oxidant [9] activities. Due to their diverse pharmacological properties, much atten-
tion has been focused on the development of novel pyrazolone derivatives in recent
years.
Cascade (domino) reactions or multi-step one-pot synthetic protocols are known
to be efcient and economical synthetic strategies for the construction of a diverse
range of heterocyclic derivatives from readily available organic substrates [10–12].
Because several similar or diferent types of reactions are performed in sequence,
simultaneously, in the same protocols, the building blocks involved in cascade
reactions often possess multiple reaction centers (or functional groups). Since the
cyclohexonedicarboxylates contain multiple functionalities, including the carbonyl,
hydroxyl, and two ester groups, they, therefore, can serve as useful synthons in vari-
ous cascade reactions to construct novel heterocyclic structures [13–16].
In continuation of our work to develop new heterocycles starting from the inter-
mediates of cyclohexonedicarboxylates [14–19], we attempted to synthesize novel
cyclohexane-annulated pyrazolones by the reaction of cyclohexonedicarboxylates
with phenylhydrazine catalyzed by sulfuric acid in the air. Unexpectedly, the reac-
tion is far more complicated than previously suspected. The reaction gave a com-
plex mixture of more than fve products together with unreacted starting materials.
Among them, three kinds of pyrazolone derivatives constructed via cascade pro-
cesses were fnally obtained. For a better understanding of this one-pot reaction,
detailed investigations including X-ray crystallography analysis were carried out to
elucidate structural properties of the new pyrazolone derivatives, and related experi-
ments were performed to determine the product distributions of this reaction. A
plausible reaction mechanism was also proposed based on those structures, and the r
esults are reported herein.
Results and discussion
In an attempt to synthesize cyclohexane-annulated N-containing heterocycles, we
conducted the reaction of ethyl 3,9-dimethyl-7-phenyl-6H-dibenzo-[b,d]pyran-
6-one-8-carboxylate (1, Scheme 1) (1.0 eq.) with phenylhydrazine (1.2 eq.) in
ethanol under refuxing conditions. The reaction was initially carried out without
any catalyst in air, and the compound 2 (Scheme 1) was obtained as an almost
1 3

A detailed investigation into the one-pot cascade reaction…
Scheme 1 The product distribution of the reaction of cyclohexonedicarboxylate 1 with phenylhydrazine
exclusive product. When concentrated sulfuric acid was added as the catalyst,
surprisingly, it indicated that, besides unreacted starting materials, more than
fve new products were presented in the crude reaction mixture. The experimen-
tal results went beyond our previously consideration. The diversity and mul-
tiple reactive sites of the starting material cyclohexonedicarboxylate 1 must be
responsible for the multiplicity and complexity of the reaction [13]. After routine
workup, three products with relatively higher yields were obtained by column
chromatography from the crude mixture using gradient elution of n-hexane/ethyl
acetate. Their structures were identifed as 2, 3 and 4 (Scheme 1), respectively.
Furthermore, extensive column and preparative thin-layer chromatography were
performed, and another two unexpected products with lower yields were obtained,
and their structures (5 and 6) were fnally identifed as described in Scheme 1.
A careful analysis of product distribution indicated that compound 2 was the
product of a simple one-step condensation of 1 with phenylhydrazine, and com-
pound 4 was a by-product due to the intramolecular dehydration of 1. The com-
pound 3 was the desired pyrazolone derivative obtained through a two-step cas-
cade reaction of condensation/self-amidation.
1 3

C.-Y. Chen et al.
Our special attention was attracted to compounds 5 and 6 because they both
contained unexpected, interesting pyrazolone structures that are otherwise dif-
fcult to synthesize. Furthermore, they were assumed to be derived from novel
triple-cascade reactions of the starting materials. Inspired by these preliminary
fndings, we further explored the structural characteristics of the interesting struc-
tures of 5 and 6 by X-ray crystallography analysis and investigated their product
distributions in diferent reaction conditions and suggested a reaction mechanism
for the formation of the products 2-6.
Firstly, since the spectroscopic data were not sufcient to establish their struc-
tures, the absolute confgurations of the compound 5 and 6 were determined by
X-ray crystallography analysis, and the crystallographic data are summarized in
Table 1.
Table 1 Crystal data and structure refnement for the compound 5 and 6
Compounds
5
6
Empirical formula
Chemical formula weight (Mr)
C23H24N2O6
424.44
C23H22N2O3
374.43
Crystal system
Space group
Triclinic
P-1
Triclinic
P-1
Unit cell dimensions
a (Å)
b (Å)
c (Å)
α (º)
10.238(2)
10.766(3)
10.819(3)
65.358(6)
73.372(6)
87.043(6)
1035.4(5)
2
10.112(2)
10.766(2)
11.031(2)
101.982(6)
115.373(6)
107.667(7)
951.1(3)
2
β (º)
γ (º)
Volume (Å3)
Z
Density (calcd.) g/cm3)
1.361
0.099
448
1.307
0.087
396
Absorption coefcient (mm−1
F(000)
)
Temperature (K)
Radiation (Å)
θ Min, max (º)
Data set
296
296
Mo Ka 0.71073
2.5, 25.0
Mo Ka 0.71073
2.3, 25.0
Limiting indices −11<h<12;
Limiting indi-
−12<k<12; −10<l<12
ces −12<h<12;
−11<k<12; −13<l<12
Total., uniq. data
R (int)
4976, 3571
0.054
6646, 3322
0.056
Nref, Npar
3571, 284
3322, 255
R, wR2, S
0.0602, 0.1770, 1.04
0.0554, 0.1527, 1.02
CCDC number
1967131
1967132
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A detailed investigation into the one-pot cascade reaction…
The single-crystal X-ray structure analysis revealed that compound 5 was an
interesting cyclohexane-annulated pyrazolone bearing a tertiary hydroperoxide
group (–OOH) (Fig. 1a); it, therefore, was the product of a condensation/self-amida-
tion/peroxidation triple-cascade reaction. As depicted in Fig. 1a, the fve-membered
pyrazolone ring in 5 is essentially planar with a deviation of less than 0.019 Å. The
cyclohexane ring which annulated to the pyrazolone ring adopts a typical chair con-
formation with C8 and C11 deviating -0.6726 and 0.6626 Å, respectively, on either
side from the best least-squares plane through atoms C9, C10, C13 and C14. The
methyl, ethoxycarbonyl and phenyl groups, respectively, at C(11), C(13) and C(14)
occupy equatorial positions. In contrast, the hydroperoxide and the hydroxyl groups,
respectively, at C(19) and C(11), are placed axially on the cyclohexane ring. The
phenyl ring attached at N1 is near coplanar with pyrazolone ring with the dihedral
angle between them being 18.199(82)°.
In addition to the single-crystal X-ray structure analysis, the high-resolution ESI
mass spectrometry (HR-ESI–MS) was also employed to further confrm the struc-
ture of 5. The HR-ESI–MS (positive-ion mode) of 5 exhibited pseudo molecular
ion peaks of [M+H]+ at m/z 425.1702 (calcd. 425.1713) and [M+Na]+ at m/z
447.1522 (calcd. 447.1532). Those MS peaks imply a molecular weight of 424.17
for 5, and the molecular formula of 5 was further confrmed to be C23H24O6N2.
The single-crystal X-ray structure analysis revealed that compound 6 was a
cyclohexene-annulated pyrazolone (Fig. 1b). Therefore, it must be derived from a
three-step cascade reaction of condensation–self-amidation–dehydration. Similar to
the structure of 5, the pyrazolone ring in 6 is planar too but is more distorted than
the corresponding pyrazolone ring in 5. The C7 is slightly displaced out of the mean
plane of N1/N2/C9/C8 by 0.1541 Å. The conformation of the six-membered car-
bon ring (C8/C9/C10/C11/C12/C13) which annulated to the pyrazolone ring in 6
is found to be signifcantly diferent from the corresponding ring in 5 as it adopts
a distorted envelope conformation with the C13 at the fap and deviates by 0.5938
Å from the mean plane of the remaining fve atoms. The dihedral angle between
the pyrazolone ring and the mean plane of the double bond (C21/C24/C29/C25)
is 17.170(106)°. The six-membered ring in 6 contains more sp2 carbon atoms and
bears only three substitution groups. These characters make it fatter and sterically
less crowded when contrast to the corresponding ring in 5.
Fig. 1 Molecule structures and ORTEP drawings of the compound 5(1a) and 6(1b)
1 3

C.-Y. Chen et al.
Scheme 2 Three tautomeric forms of pyrazolones
Table 2 Optimization of the reaction conditions for the reaction of 1 with phenylhydrazine
Entry Catalyst
Atmosphere Solvent Temperature (°C) Time (h) Conversion (%)
2
3
4
5
6
1
2
3
4
5
6
7
8
H2SO4
H2SO4
H2SO4
Air
N2
O2
EtOH
EtOH
EtOH
THF
Toluene Refux
EtOH
EtOH
Refux
Refux
Refux
Refux
6
6
6
6
6
6
6
6
6
26 18 15
30 21 17
23 20 18 10 15
7
–
13
16
BF3·OEt2 O2
35 14 10
32 12
21 20 15
4
5
8
8
8
16
AlCl3
p-TsOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
O2
O2
O2
O2
O2
O2
O2
O2
O2
9
Refux
Refux
19 23 16 12 18
Toluene Refux
26 19 16
25 22 14
28 20 12
18 19 17 13 20
15 17 18 15 22
6
6
5
14
11
14
9
DMSO
EtOAc
EtOH
EtOH
EtOH
80
10
11
12
13
Refux
Refux
Refux
Refux
6
10
14
18
20 18 20
9
16
It is well known that when a hydrogen atom exists on the 4-position, the pyra-
zolones can adopt three tautomeric forms defned as CH–, OH–, and NH-forms
[20–22], respectively (Scheme 2). In the present X-ray structure analysis, the
results showed that compounds 5 and 6 both exist in the CH-form. It should be
noted that due to the absence of hydrogen atom on 4-position, the tautomerization
of compound 5 is thus prohibited and therefore can only exist in the CH-form.
In order to improve the product selectivity, especially for the desired com-
pounds of 5 and 6, some critical reaction parameters were examined (Table 2).
Firstly, to verify whether molecular oxygen (O2) in the air was involved in the for-
mation of the hydroperoxide group in compound 5, the reaction was thus carried
out under O2 and Ar atmosphere instead of air, respectively. When the reaction
was performed under Ar atmosphere, the product of 5 was no longer obtained
(entry 2). On the other hand, when the reaction was carried out under O2 atmos-
phere, the yield of 5 increased by 10% (entry 3). These results indicated that O2 is
necessary for the formation of compound 5. Secondly, considering that acid-cat-
alysts can activate the carbonyl, hydroxyl and ester groups in 1, other Lewis and
Bronsted acids were screened instead of H2SO4 to catalyze the reaction (entries
1 3

A detailed investigation into the one-pot cascade reaction…
4–7). It is found that BF3·OEt2, AlCl3, and p-TsOH were all less efective than
H2SO4, while trifuoromethanesulfonic acid (TfOH) was proved to be more ef-
cient than H2SO4 and therefore further used for optimization (entry 7). The infu-
ence of solvents and reaction time were also investigated. Among all the tested
solvents, the protic solvent of ethanol performed the best under refuxing condi-
tions (entries 8–10). The total yields of 5 and 6 increased with the extension of
the reaction time from 6 to 14 h. When a longer reaction time was applied, the
yields decreased due to increased side product formation.
To our disappointment, it has to be noted that, due to the stereo-hindrance efects
caused by the cyclohexane rings in starting material and the intermediates, and,
together with the competitions between diferent reactions involved in the process,
the regio- and stereo-selectivities of this reaction remain insufcient. The yields of
the two triple-cascade reactions (the condensation/amidation/peroxidation reaction
and the condensation/amidation/dehydration reaction) are still unsatisfactory, and
further eforts are still ongoing to achieve more efcient procedures.
Based on the above studies and literature reports [23, 24], we proposed the fol-
lowing mechanism for the formation of compound 5 and 6 (Scheme 3). Firstly, the
1-carbonyl group in compound 1, which is activated by the TfOH and the activated
carbonyl, undergoes condensation with phenylhydrazine to attain compound 2. A
subsequent intramolecular amidation of the ester group at 2-position in 2 with the
elimination of ethanol attains compound 3. After the important intermediate 3 is
Scheme 3 The proposed mechanism for the formation of the compounds 5 and 6
1 3

C.-Y. Chen et al.
generated, the following transformations can proceed along two reaction pathways.
In one of them, compound 3 is easily transformed from CH-form into its OH-form
through tautomerization [20–22]; then, the OH-form tautomer performs an ene reac-
tion (or Schenck ene reaction) [23, 24] with O2 to give compound 5. In this process,
the OH-form tautomer of compound 3 acts as an ene component and the O2 serves
as an enophile component, and the peroxidation proceeds through a six-membered
cyclic transition state [23, 24]. Alternatively, when the 5-hydroxyl group in com-
pound 3 is protonated by acid and then removed in form of water, compound 6 can
be accessed from compound 3 along another pathway.
Conclusions
In conclusion, when conducting the reaction of ethyl 3,9-dimethyl-7-phenyl-
6H-dibenzo-[b,d]pyran-6-one-8-carboxylate with phenylhydrazine catalyzed by
the acid in the air, up to fve products were obtained through elaborate separation
and purifcation. Among these fve products, absolute confgurations of the two
unexpected, interesting pyrazolones (the compound 5 and 6) were both unambig-
uously identifed by single-crystal X-ray structure analysis. The product distribu-
tion of this reaction depended on the reaction conditions, and the yields reached
to 15% and 22% for the compounds 5 and 6, respectively, after reaction optimiza-
tion. A reaction mechanism for the formation of the fve products was discussed,
and compound 5 was suggested as the product of three-step cascade reactions of
condensation/amidation/peroxidation, and compound 6 was proposed as the prod-
uct from the reaction of condensation/amidation/dehydration.
Experimental section
General
All commercially available chemicals were purchased as reagent grade and used
without further purifcation. The thin-layer chromatography (TLC) was carried
out on glass plates coated with silica gel (Qingdao Haiyang Chemical Co., Gel 60
F-254) and visualized by UV lights (254 nm and 365 nm). 1H and 13C NMR spectra
were determined on Brucker ARX-400 (400 MHz, Bruker, Rheinstetten/Karlsruhe,
Germany) with TMS as an internal standard. The abbreviations s, d, t, q and m refer
to singlet, doublet, triplet, quadruplet and multiplet, respectively. HRMS were per-
formed on an Agilent 6540Q-TOF LC/MS equipped with electrospray ionization
(ESI) probe operating in positive or negative ion mode. Mass spectra (ESI) were
obtained on a Finnigan-Mat LCQ mass spectrometer (Thermo Finnigan, San Jose,
CA). Melting points were determined on an electrically heated RK-Z melting point
apparatus (Analytical Instrument Factory in Tianjin, China) and were uncorrected.
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A detailed investigation into the one-pot cascade reaction…
Synthesis of the starting material 1
Compound 1 was prepared similar to our previous report [18, 19], and the procedure
was as follows: to 20 mL of anhydrous ethanol in fask was added 2.66 g ethyl ace-
toacetate (20.4 mmol) and 1.06 g benzaldehyde (10.0 mmol) under stirring at room
temperature. Piperidine (0.5 mL) was added dropwise, and the solution was heated
to refux for 10 min and then stirred for 24 h at room temperature. The precipitate
formed was fltered and purifed by recrystallization from ethanol. Pure compound 1
was obtained as a white solid in 83% yield, m.p.: 154–155 °C.
Typical procedure for the reaction of 1 with phenylhydrazine
To a solution of compound 1 (2.0 mmol) and phenylhydrazine (2.4 mmol) in EtOH
(30.0 mL), TfOH was added dropwise (0.18 mL, 2 mmol), with the resulting mixture
being stirred under an oxygen balloon for 6–18 h at refux. After cooling, the solvent
was evaporated, and the residue was dissolved in 50 mL CHCl3, which was washed
with 5% NaHCO3. The organic phase was separated, dried over Na2SO4 and con-
centrated in vacuo. The residue was subjected to column chromatography (300–400
mesh) and eluted with gradient elution of EtOAc/Hexane (from 1:20 to 1:4, v/v) to
yield compounds 2–6. Preparative thin-layer chromatography was proved to also be
suitable for separation them using similar gradient elution conditions.
Diethyl 4‑hydroxy‑4‑methyl‑2‑phenyl‑6‑(2‑phenylhydrazono)cyclohexane‑1,3‑dicarbo-
xylate (2) White solid, m.p.: 202–204 °C. 1H NMR (400 MHz, DMSO-d6) δ(ppm):
9.64(s, 1H), 7.29–7.21(m, 4H), 7.17–7.13(m, 2H), 6.98(d, J=8.0 Hz, 2H), 6.84(s,
1H), 6.70(t, J=8.0 Hz, 1H), 3.95–3.86(m, 5H), 3.67(d, J=12.0 Hz, 1H), 3.46(d,
J=12.0 Hz, 1H), 3.43(d, J=12.0 Hz, 1H), 1.87(s, 3H), 0.943(t, J=8.0 Hz, 3H),
0.939(t, J=8.0 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ(ppm): 171.5, 157.8,
148.4, 147.2, 136.0, 128.8, 127.8, 124.9, 120.5, 118.5, 113.7, 60.5, 55.0, 53.7, 36.3,
30.9, 23.7, 22.0, 14.0. MS (ESI) m/z [M+H]+ calcd. for C25H31N2O5: 439.2; found:
439.3.
Ethyl
6‑hydroxy‑6‑methyl‑3‑oxo‑2,4‑diphenyl‑3,3a,4,5,6,7‑hexahydro‑2H‑inda-
1
zole‑5‑carboxylate (3) Faint yellow solid, m.p.: 244–246 °C. H NMR (400 MHz,
DMSO-d6) δ(ppm): 10.84(s, 1H), 7.65(d, J=8.0 Hz, 2H), 7.40–7.36(m, 3H),
7.28(d, J=8.0 Hz, 2H), 7.16–7.14(m, 3H), 4.75(s, 1H), 4.00–3.93(m, 3H), 2.91(d,
J=16.0 Hz, 1H), 2.68(d, J=12.0 Hz, 1H), 1.28(s, 3H), 1.02(t, J=8.0 Hz, 3H).
13C NMR (100 MHz, DMSO-d6) δ(ppm): 172.3, 168.6, 158.4, 145.1, 137.9, 135.2,
131.0, 129.2, 128.9, 124.6, 119.3, 113.6, 112.7, 60.4, 60.2, 55.0, 48.3, 44.9, 43.5,
20.9, 13.8. MS (ESI) m/z [M+H]+ calcd. for C23H25N2O5: 393.2; found:393.4.
Diethyl 5‑methyl‑3‑oxo‑1,21,3,6‑tetrahydro‑[1,1’‑biphenyl]‑2,6‑dicarboxylate (4) White
solid, m.p.: 177–179 °C. H NMR (400 MHz, CDCl3) δ(ppm): 7.31–7.22(m, 5H),
6.09(s, 1H), 4.02–3.93(m, 5H), 3.68(d, J=16.0 Hz, 1H), 3.64(d, J=12.0 Hz, 1H),
1 3

C.-Y. Chen et al.
1.99(s, 3H), 1.02(t, J=8.0 Hz, 3H), 0.99(t, J=8.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ(ppm): 192.3, 170.6, 168.4, 156.9, 138.1, 128.7, 127.9, 127.4, 61.2, 61.0,
59.2, 54.7, 47.0, 21.9, 13.90, 13.88. MS (ESI) m/z [M+H]+ calcd. for C19H23O5:
331.1; found:330.9.
Ethyl
3a‑hydroperoxy‑6‑hydroxy‑6‑methyl‑3‑oxo‑2,4‑diphenyl‑3,3a,4,5,6,7‑hexahy-
dro‑2H‑indazole‑5‑carboxylate (5) Colorless crystal, m.p.: decomposed>110 °C.
1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.81(d, J=8.0 Hz, 2H), 7.43(t, J=8.0 Hz,
2H), 7.23–7.17(m, 6H), 6.59(s, 1H), 4.84(s, 1H), 3.80–3.66(m, 2H), 3.36(s, 2H),
2.86(d, J=12.0 Hz, 1H), 2.58(d, J=12.0 Hz, 1H), 1.38(s, 3H), 0.74(t, J=8.0 Hz,
3H). 13C NMR (100 MHz, DMSO-d6) δ(ppm): 171.5, 170.4, 162.5, 138.1, 135.5,
128.9, 127.0, 126.8, 124.6, 118.0, 75.4, 72.1, 59.5, 53.1, 47.8, 40.0, 28.6, 13.6.
HRMS (ESI) m/z [M+H]+ calcd. for C23H25N2O6: 425.1713; found: 425.1702;
[M+Na]+ calcd. for C23H24N2O6Na: 447.1532; found: 447.1522.
Ethyl
6‑methyl‑3‑oxo‑2,4‑diphenyl‑3,3a,4,5‑tetrahydro‑2H‑indazole‑5‑carboxylate
1
(6) Colorless crystal, m.p.: 252–254 °C. H NMR (400 MHz, DMSO-d6) δ(ppm):
7.77(d, J=8.0 Hz, 2H), 7.43–7.39(m, 4H), 7.28–7.25(m, 3H), 6.88(s, 1H), 6.49(s,
1H), 4.14–4.06(m, 1H), 3.94(d, J=8.0 Hz, 1H), 3.87(q, J=8.0 Hz, 2H), 1.91(s,
3H), 0.86(t, J=8.0 Hz, 3H). 13C NMR (100 MHz, DMSO-d6) δ(ppm): 171.0, 169.6,
159.3, 146.5, 135.3, 130.1, 128.8, 128.3, 127.4, 118.1, 73.1, 60.4, 52.0, 49.5, 21.1,
13.7. MS (ESI) m/z [M+H]+ calcd. for C23H23N2O3: 375.2; found: 375.0.
X‑ray crystallography
The analytical crystalline samples of compound 5 were cultured from a mixture
solution of chloroform and n-hexane, while the suitable crystals from compound
6 were obtained by slow evaporation from n-hexane/ethyl acetate mixture. X-Ray
crystallography measurements were made on a Bruker Apperx II difractometer
with graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å).
The structures were solved by direct methods, and the non-hydrogen atoms
were located from the trial structures and then refned anisotropically with
SHELXTL using full-matrix least-squares procedures based on F2 values. Hydro-
gen atom’s positions were fxed geometrically at calculated distances and allowed
to ride on the parent atoms. CCDC reference numbers 1967131 and 1967132 con-
tain the supplementary crystallographic data reported in this paper as CIF fles.
These data sets can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif, and are also avail-
able as supporting information.
Acknowledgements This work was supported by the National Natural Science Foundation of China
(Grant Number 51872140).
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A detailed investigation into the one-pot cascade reaction…
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Afliations
Chao‑Yue Chen1 · Yu Qiao1 · Lei Zhang1 · Xin Wang1 · Ting‑Hai Yang1,2
*
Ting-Hai Yang
tinghai_yang@hotmail.com
1
2
School of Chemistry and Environmental Engineering, Jiangsu University of Technology,
Changzhou 213001, People’s Republic of China
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing 210093, People’s Republic of China
1 3