A new tandem synthesis of bis(β,β′-dialkoxy carbonyl) compounds by oxidative cleavage of aziridines under metal-free conditions

Article abstract of DOI:10.1039/c9ob02451d

An efficient and new approach has been developed to synthesize bis(β,β′-dialkoxy carbonyl) derivatives through the reaction between N-tosylaziridines and malonate esters under ambient air using ^tBuOK in DMSO solvent. A plausible reaction pathway has been predicted. Control experiments suggested that the reactions proceed through the formation of α-aminoketones. This reaction offers a broad substrate scope, metal-free synthesis, excellent regioselectivity, easily accessible reactants, and simple operation. A gram-scale synthesis demonstrates the potential applications of the present method.

Full text of DOI:10.1039/c9ob02451d

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A new tandem synthesis of bis(β,β’-dialkoxy
carbonyl) compounds by oxidative cleavage
Cite this: DOI: 10.1039/c9ob02451d
of aziridines under metal-free conditions†
Satyajit Samanta, a Sougata Santra, b Rana Chatterjee a and
a
Adinath Majee
*
An efficient and new approach has been developed to synthesize bis(β,β’-dialkoxy carbonyl) derivatives
t
through the reaction between N-tosylaziridines and malonate esters under ambient air using BuOK in
Received 13th November 2019,
Accepted 16th December 2019
DMSO solvent. A plausible reaction pathway has been predicted. Control experiments suggested that the
reactions proceed through the formation of α-aminoketones. This reaction offers a broad substrate
scope, metal-free synthesis, excellent regioselectivity, easily accessible reactants, and simple operation. A
gram-scale synthesis demonstrates the potential applications of the present method.
DOI: 10.1039/c9ob02451d
rsc.li/obc
obtain α-sulfonylamino ketones followed by tandem difunctio-
Introduction
nalization with malonate esters in the presence of DMSO as an
In modern organic synthesis, tandem reactions (domino or oxygen donor and tBuOK as a base.
cascade reactions) are one of the most powerful and atom
Recently, significant attention has been paid to the chemi-
economical methodologies.1 These reactions usually proceed cal reactivity of dimethyl sulfoxide (DMSO) apart from its use
in a more efficient and environmentally benign manner than as a solvent. The utility of DMSO as a reagent has been well
conventional procedures by omitting the steps of separation established because it is an important carbon source for
and purification of the reaction intermediates. Bis CvO,5 Me,6 SMe,7 SO2CH3,8 and –CN formation,9 and an
(β-dimethoxy carbonyl) derivatives are used as bone affinity oxygen donor.10 Very recently, we developed an efficient
agents in the treatment of bone diseases.2 In addition, in method for the synthesis of α-sulfonylamino ketones through
industrial chemistry, these derivatives are also very useful as the reaction between terminal alkynes and sulfonamides.11
precursors for the preparation of glutaric acid.3 Due to their These α-sulfonylamino ketones serve as valuable intermediates
immense pharmaceutical activities, synthesis of bis for the synthesis of 2-amino alcohols12 and various nitrogen-
(β-dimethoxy carbonyl) derivatives is important. However, to containing heterocycles.13 In this manuscript, we are pleased
the best of our knowledge, only very few methods are found in to report a convenient and simple procedure for the synthesis
the literature for the synthesis of this scaffold.4 Baranac- of bis(β,β′-dialkoxy carbonyl) derivatives through the reaction
Stojanović et al.4a synthesized this compound with only 6%
yield, and later, in 2014, the Zha and Wang group obtained
these compounds by difunctionalization of aryl ketones with
malonate esters via electrochemical oxidation (Scheme 1a).4b
The second approach is better in terms of yield but needs
special requirements which are not suitable for a common lab-
oratory setup. In this context, we developed a convenient
method which involves oxidative ring opening of aziridines to
aDepartment of Chemistry, Visva-Bharati (A Central University), Santiniketan
731235, India. E-mail: adinath.majee@visva-bharati.ac.in
bDepartment of Organic and Biomolecular Chemistry, Chemical Engineering
Institute, Ural Federal University, 19 Mira Street, 620002 Yekaterinburg, Russian
Federation
†Electronic supplementary information (ESI) available: Experimental procedure
and scanned copies of 1H and 13C NMR spectra of the synthesized compounds.
See DOI: 10.1039/c9ob02451d
Scheme 1 Different precursors for the synthesis of bis(β,β’-dimethoxy
carbonyl) compounds.
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between N-tosylaziridines and malonate esters under ambient of a very strong bulky base, tBuOK, and 88% yield was obtained
t
air using BuOK in DMSO solvent (Scheme 1b). In this pro- (entry 6, Table 1). By decreasing the amount of the base the
cedure, sulfonylamino ketones were obtained in situ from aziri- yield decreased (76%) and by increasing the amount of the
dines in DMSO solvent and transformed into the key com- base to 2 equiv. the yield decreased further (85%) (entries 7
pounds, bis(β,β′-dialkoxy carbonyl) derivatives, via a tandem and 8, Table 1). Other common organic solvents (such as
process. The reaction conditions are mild and metal-free, and CH3CN, toluene, 1,2-DCE, and DCM) were not so effective for
the products are obtained in good yields in a very short reac- this conversion (entries 9–12, Table 1). Furthermore, we
tion time at room temperature. To the best of our knowledge, observed that the reaction did not proceed without a base in
this is the first report where aziridines have been used to syn- DMSO (entry 13, Table 1). Finally, the optimized reaction con-
thesize bis(β,β′-dialkoxy carbonyl) derivatives.
ditions were achieved by carrying out the reaction in DMSO at
100 °C for 45 min and then in the presence of malonate ester
(2 equiv.) with 1 equiv. of BuOK at room temperature for
t
another 45 min under ambient air (entry 6, Table 1).
Results and discussion
With the optimized reaction conditions in hand, the sub-
strate scope of this tandem protocol was investigated, and the
results are presented in Scheme 2. Substrate scopes were
achieved by using various substituted aziridines (1) with
different active methylene containing nucleophiles such as
dimethyl malonate (DMM, 2a) and diethyl malonate (DEM,
2b). During optimization, we observed that 2-phenyl-1-tosyla-
ziridine (1a) reacted with DMM (2a) to afford an excellent yield
(3aa, 88%). N-Tosyl aziridine with an electron-donating substi-
tuent (such as –Me) at the ortho- and para-positions of the
We started our study by mixing 2-phenyl-1-tosylaziridine (1a,
1 mmol) in DMSO (2 mL), and the reaction mixture was stirred
at 100 °C for 45 min. Next, 2 equiv. of dimethyl malonate (2a)
and 1 equiv. of K2CO3 were added to the reaction mixture and
stirred for another 45 min at room temperature. Gratifyingly,
the expected bis(β,β′-dimethoxy carbonyl) compound (tetra-
methyl 2-benzoylpropane-1,1,3,3-tetracarboxylate, 3aa) was
obtained in 55% yield. Encouraged by this result, we carried
out the reaction under different conditions to optimize the
reaction conditions, and the results are summarized in
Table 1. First, we optimized the solvent and temperature. In
the presence of 1 equiv. of mild bases such as K2CO3 and
Cs2CO3 the desired product was obtained in 55% and 70%
yields, respectively (entries 1 and 2, Table 1), whereas by using
Et3N (1 equiv.), only 23% yield was obtained (entry 3, Table 1).
By using other organic bases such as 1,8-diazabicyclo[5.4.0]
undec-7-ene (DBU) and 1,4-diazabicyclo[2.2.2]octane (DABCO),
the yield increased up to 72% and 74%, respectively (entries 4
and 5, Table 1). The best result was obtained by using 1 equiv.
Table 1 Optimization of the reaction conditionsa
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CH3CN
Toluene
1,2 DCE
DCM
K2CO3 (1 equiv.)
CS2CO3 (1 equiv.)
Et3N (1 equiv.)
DBU (1 equiv.)
DABCO (1 equiv.)
tBuOK (1 equiv.)
tBuOK (0.5 equiv.)
tBuOK (2 equiv.)
tBuOK (1 equiv.)
tBuOK (1 equiv.)
tBuOK (1 equiv.)
tBuOK (1 equiv.)
—
55
70
23
72
74
88
76
85
32
20
25
27
NDc
9
10
11
12
13
DMSO
Scheme 2 Tandem synthesis of bis(β,β’-dialkoxy carbonyl) derivatives
from aziridines. Reaction conditions: All reactions were carried out on a
1 mmol scale; 1 (1 mmol), 2 (2 mmol), and tBuOK (1 equiv.) in DMSO
(2 mL). All are isolated yields.
a Reaction conditions: 1 mmol of 1a, 2 mmol of 2a in the presence of
the solvent (2 mL) and bases (as stated). b All are isolated yields. c Not
detected in TLC.
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phenyl ring reacted with 2a to afford the corresponding bis
(β-dimethoxy carbonyl) derivatives (3ba and 3da) in excellent
yields. But when the –Me substituent was present at the meta-
position the yield slightly decreased (3ca, 70%). Electron-with-
drawing groups (such as –chloro and –bromo) on the phenyl
ring of the aziridine moiety at different positions efficiently
reacted with DMM and offered good yields. For example,
bromo-substituted aziridines at the meta- (3ea) and para- (3fa)
positions gave the desired products in 71% and 74% yields,
respectively (3ea and 3fa). On the other hand, for chloro-substi-
tuted aziridines at the ortho- and para-positions the yields were
better (75% and 80% for 3ga and 3ha, respectively). This strat-
egy was also extended to another malonate ester (such as
DEM, 2b) to prove the general applicability of the present pro-
cedure which was a disadvantage of the previous methods.4b
Simple 2-phenyl-1-tosylaziridine (1a) reacted with 2b very
smoothly and gave an excellent yield (3ab, 86%). Compounds
having electron-donating substituents at the ortho- and meta-
positions gave the products (3bb and 3cb) in 81% and 70%
yields, respectively. It is also worth noting that with the elec-
tron-donating substituent (–Me) at the para-position, the yield
amusingly increased (3db, 86%). With electron withdrawing
groups such as –bromo at the meta- and para-positions of the
phenyl ring of the aziridine moiety, 72% and 76% yields were
obtained (3eb and 3fb), respectively, whereas the presence of
the –chloro substituent at the ortho- and para-positions gave
better yields (78% for 3gb and 82% for 3hb).
It is worth mentioning that when we used chloromethyl-
substituted tosylaziridine 1i we obtained the dehalogenated
products (4aa and 4ab) under the same reaction conditions
(Scheme 3). We did not carry out any further experiments to
determine the exact mechanism but we assume that this type
of dehalogenation may be the result of simple elimination of
halogen by the hydride ion from the nitrene intermediate.
Moreover, the impending synthetic applicability of this pro-
tocol was investigated at the gram scale using the model reac-
tion in our laboratory setup. As shown in Scheme 4, the reac-
tion could afford 1.6 g of 3aa in 85% yield without any signifi-
cant loss of efficiency, demonstrating the potential appli-
cations of the present method for the large-scale synthesis of
bis(β-dimethoxy or β-diethoxy carbonyl) derivatives.
Scheme 4 Gram-scale synthesis.
characterized by spectral data and the new compounds by
spectral and analytical data. The reaction conditions were mild
enough and caused no decomposition of the products or
polymerization of the starting materials. We did not observe
any by-products for all the reaction combinations giving rise to
high yields of the desired products and regioselectivity of the
protocol.
A few control experiments were carried out to obtain a
better understanding of the mechanistic pathway of the reac-
tion (Scheme 5). First of all, we synthesized the corresponding
α-aminoketone (5a) according to our previously reported
method.11 In addition, when 2-phenyl-1-tosylaziridine (1a) was
treated with dry DMSO at 100 °C for 45 min α-aminoketone
(5a) was obtained in 86% yield (Scheme 5a). The same reaction
under an argon atmosphere also gave a satisfactory yield
(Scheme 5b) which proves that the oxygen comes from the
DMSO solvent. But the reaction of aziridine (1a) using mole-
cular oxygen in 1,2-DCE produced no α-aminoketone (5a)
(Scheme 5c). Next, when α-aminoketone (5a) was subjected to
the optimized reaction conditions, the corresponding desired
final product 3aa was obtained in
a
quantitative yield
It is worth mentioning that all these reactions were per-
formed in an open atmosphere and are not sensitive to air and
moisture. All the known synthesized compounds have been
Scheme 3 Observations for the reaction of chloromethyl-substituted
tosylaziridine (1i).
Scheme 5 Control experiments.
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that the reactions proceeded through the formation of
α-aminoketones. The notable advantages of the present meth-
odology are clean reaction, easily accessible reactants, ease of
product isolation/purification, and metal-free and environ-
mentally friendly reaction conditions. A gram-scale synthesis
demonstrates the potential applications of the present
method. We believe that the present methodology opens a new
door to synthesize important building blocks of bis(β,β′-dia-
lkoxy carbonyl) derivatives.
Experimental
General information
All reagents were purchased from commercial sources and
used without further purification. 1H NMR spectra were
recorded on a 400 MHz spectrometer in CDCl3 solution.
Chemical shifts are expressed in parts per million (δ) and the
signals are reported as s (singlet), d (doublet), t (triplet), m
(multiplet), and dd (double doublet), and coupling constants
(J) are given in Hz. 13C NMR spectra were recorded at 100 MHz
in CDCl3 solution. Chemical shifts as internal standard are
referenced to CDCl3 (δ = 7.26 for 1H and δ = 77.16 for 13C
NMR). TLC was performed on silica gel coated glass slides. All
solvents were dried and distilled before use.
Scheme 6 Probable mechanism.
(Scheme 5d). Furthermore, α-aminoketone (5a) was isolated
from the reaction mixture by quenching the reaction after
45 min. These results indicate that the reaction proceeds
through the formation of α-aminoketone (5a). In addition, we
did not observe the formation of phenylglyoxal (6a) when
α-aminoketone (5a) was treated with
a base in DMSO
(Scheme 5e). Even under the standard reaction conditions,
phenylglyoxal (6a) did not afford the desired condensed
product (3aa) by reacting with DEM (Scheme 5f) which indi-
cated that no such intermediate (6a) was formed during the
reaction.
General procedure for the synthesis of compounds 3
1 mmol of aziridine (1) and 2 mL of DMSO were taken in a dry
sealed tube and then the resulting mixture was stirred and
heated at 100 °C for 45 min. After this, the resulting mixture
was cooled to room temperature and dimethyl malonate or
diethyl malonate (2, 2 equiv.) and tBuOK (1 equiv.) were added
into the same reaction vessel. The final mixture was stirred at
room temperature for 45 min (monitored by TLC). The reac-
tion mixture was diluted with ethyl acetate (10 mL) and water
(10 mL). Then the organic layer was dried over anhydrous
Na2SO4. After evaporation of the solvent, the crude product
was collected and purified by column chromatography on
silica gel using petroleum ether and ethyl acetate as the
eluent.
Based on the literature reports14,15 and our control experi-
ments, a probable mechanism is proposed in Scheme 6. In the
first step, 2-phenyl-N-tosylaziridine (1a) forms α-aminoketone
(5a) as an intermediate by oxidative cleavage in the presence of
DMSO according to the literature.14 In the presence of a base
this α-aminoketone (5a) releases a proton to produce an anionic
intermediate (A). In the next step a nitrene intermediate (B)15 is
formed by the elimination of a –tosyl (Ts) group from the inter-
mediate A. This nitrene intermediate (B) produces imine (C) by
rearrangement. This intermediate imine (C) is the key com-
ponent of the reaction, where, in the first step the nucleophilic
addition of the active nucleophile of malonate ester produces
another intermediate (D). The final step involves the substi-
tution of the amino group of the intermediate D by another
nucleophile which gives the desired product (3aa).
Characterization data for 3 and 5a
Tetramethyl 2-benzoylpropane-1,1,3,3-tetracarboxylate (3aa).4b
Pale yellow oil (334 mg, 88%); 1H NMR (CDCl3, 400 MHz):
δ 8.01–7.99 (m, 2H), 7.59–7.55 (m, 1H), 7.55–7.45 (m, 2H), 4.87
(t, J = 8.0 Hz, 1H), 4.11 (d, J = 8.0 Hz, 2H), 3.72 (s, 6H), 3.53 (s,
6H); 13C NMR (CDCl3, 100 MHz): δ 198.9, 168.3, 168.1, 136.4,
Conclusions
To conclude, we successfully developed an efficient method- 133.6, 129.0, 128.7, 53.1, 52.9, 52.4, 44.1.
ology for the synthesis of bis(β,β′-dialkoxy carbonyl) derivatives
Tetramethyl 2-(2-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
by the reaction of N-tosylaziridines with malonate esters in the late (3ba).4b Pale yellow oil (315 mg, 80%); 1H NMR (CDCl3,
t
presence of BuOK in DMSO at 100 °C to room temperature 400 MHz): δ 7.87–7.85 (m, 1H), 7.39–7.35 (m, 1H), 7.30–7.28
under ambient air. An array of bis(β,β′-dialkoxy carbonyl) (m, 1H), 7.24–7.22 (m, 1H), 4.77 (t, J = 8.0 Hz, 1H), 4.05 (d, J =
derivatives with broad functionalities has been synthesized in 8.0 Hz, 2H), 3.65 (s, 6H), 3.60 (s, 6H), 2.44 (s, 3H); 13C NMR
high yields. We also proposed a mechanistic pathway for the (CDCl3, 100 MHz): δ 200.9, 168.0, 167.9, 139.4, 136.5, 131.8,
formation of these compounds. Control experiments suggested 131.7, 129.5, 125.6, 52.8, 52.8, 51.5, 47.2, 20.6. HRMS
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(ESI-TOF) m/z: [M + H]+ calcd for C19H22O9 395.1337; found 129.5, 125.4, 61.9, 61.8, 52.0, 46.9, 20.7, 13.8, 13.8. Anal. calcd
395.1338.
for C23H30O9: C, 61.32; H, 6.71; found: C, 61.41; H, 6.81.
Tetramethyl 2-(3-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
Tetraethyl 2-(3-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
late (3ca).4b Light yellow oil (276 mg, 70%); 1H NMR (CDCl3, late (3cb). Pale yellow oil (315 mg, 70%); 1H NMR (CDCl3,
400 MHz): δ 7.82–7.80 (m, 2H), 7.39–7.34 (m, 2H), 4.86 (t, J = 400 MHz): δ 7.83–7.81 (m, 2H), 7.36–7.34 (m, 2H), 4.84 (t, J =
8.0 Hz, 1H), 4.11 (d, J = 8.0 Hz, 2H), 3.72 (s, 6H), 3.54 (s, 6H), 8.4 Hz, 1H), 4.17–4.15 (m, 4H), 4.07 (d, J = 8.0 Hz, 2H),
2.41 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 198.8, 168.1, 168.0 3.99–3.96 (m, 4H), 2.40 (s, 3H), 1.23 (t, J = 7.2 Hz, 6H), 1.12 (t,
138.4, 136.2, 134.3, 129.3, 128.4, 126.2, 52.9, 52.8, 52.2, 44.1, J = 7.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 193.6, 168.0,
21.3.
167.8, 138.4, 134.3, 130.0, 129.5, 128.5, 126.4, 62.0, 52.8, 43.9,
Tetramethyl 2-(4-methylbenzoyl)propane-1,1,3,3-tetracarboxy- 14.0, 13.8. Anal. calcd for C23H30O9: C, 61.32; H, 6.71; found:
late (3da).4b Pale yellow oil (335 mg, 85%); 1H NMR (CDCl3, C23H30O9: C, 61.42; H, 6.65.
400 MHz): δ 7.92–7.90 (m, 2H), 7.28–7.26 (m, 2H), 4.85 (t, J =
Tetraethyl 2-(4-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
8.4 Hz, 1H), 4.10 (d, J = 8.0 Hz, 2H), 3.72 (s, 6H), 3.53 (s, 6H), late (3db). Pale yellow oil (387 mg, 86%); 1H NMR (CDCl3,
2.40 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 198.4, 168.3, 168.1, 400 MHz): δ 7.93–7.91 (m, 2H), 7.26–7.23 (m, 2H), 4.83 (t, J =
144.6, 133.8, 129.4, 129.2, 53.0, 52.9, 52.4, 44.0, 21.8.
8.0 Hz, 1H), 4.19–4.13 (m, 4H), 4.06 (d, J = 8.0 Hz, 2H),
Tetramethyl 2-(3-bromobenzoyl)propane-1,1,3,3-tetracarboxy- 4.05–3.93 (m, 4H), 2.39 (s, 3H), 1.23 (t, J = 7.2 Hz, 6H), 1.10 (t,
late (3ea). Pale yellow oil (326 mg, 71%); 1H NMR (CDCl3, J = 7.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 198.4, 168.0,
400 MHz): δ 8.11 (t, J = 1.6 Hz, 1H), 7.96–7.94 (m, 1H), 167.8, 144.3, 134.2, 129.3, 129.2, 62.0, 52.9, 43.6, 21.8, 14.0,
7.71–7.68 (m, 1H), 7.36 (t, J = 8.0 Hz, 1H), 4.78 (t, J = 8.0 Hz, 13.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C23H30O9:
1H), 4.09 (d, J = 8.0 Hz, 2H), 3.73 (s, 6H), 3.57 (s, 6H); 13C NMR 451.1963; found: 451.1961.
(CDCl3, 100 MHz): δ 197.9, 168.1, 167.9, 138.4, 136.3, 131.9,
130.2, 127.7, 123.0, 53.1, 53.0, 52.5, 44.1. Anal. calcd for late (3eb). Light yellow oil (371 mg, 72%); 1H NMR (CDCl3,
C18H19BrO9: C, 47.08; H, 4.17; found C, 47.15; H, 4.25. 400 MHz): δ 8.14–8.13 (m, 1H), 7.98–7.95 (m, 1H), 7.69–7.67
Tetraethyl 2-(3-bromobenzoyl)propane-1,1,3,3-tetracarboxy-
Tetramethyl 2-(4-bromobenzoyl)propane-1,1,3,3-tetracarboxy- (m, 1H), 7.37–7.33 (m, 1H), 4.76 (t, J = 8.0 Hz, 1H), 4.18–4.16
late (3fa).4b Pale yellow oil (339 mg, 74%); 1H NMR (CDCl3, (m, 4H), 4.06–4.00 (m, 6H), 1.24 (t, J = 7.2 Hz, 6H), 1.14 (t, J =
400 MHz): δ 7.89–7.87 (m, 2H), 7.63–7.61 (m, 2H), 4.80 (t, J = 7.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 197.9, 167.8, 167.6,
8.0 Hz, 1H), 4.09 (d, J = 8.0 Hz, 2H), 3.73 (s, 6H), 3.56 (s, 6H); 138.8, 136.2, 131.9, 130.1, 127.8, 122.9, 62.2, 53.0, 43.8, 14.0,
13C NMR (CDCl3, 100 MHz): δ 198.2, 168.2, 168.1, 132.5, 132.0, 13.9. Anal. calcd for C22H27BrO9: C, 51.27; H, 5.28; found: C,
130.6, 128.5, 53.1, 53.0, 52.6, 43.9.
51.32; H, 5.20.
Tetramethyl 2-(2-chlorobenzoyl)propane-1,1,3,3-tetracarboxy-
Tetraethyl 2-(4-bromobenzoyl)propane-1,1,3,3-tetracarboxy-
late (3ga). Light yellow oil (311 mg, 75%); 1H NMR (CDCl3, late (3fb).4b Pale yellow oil (391 mg, 76%); 1H NMR (CDCl3,
400 MHz): δ 7.79–7.77 (m, 1H), 7.41–7.34 (m, 3H), 4.85 (t, J = 400 MHz): δ 7.91–7.89 (m, 2H), 7.61–7.59 (m, 2H), 4.78 (t, J =
7.6 Hz, 1H), 4.06 (d, J = 7.2 Hz, 2H), 3.69 (s, 6H), 3.65 (s, 6H); 8.8 Hz, 1H), 4.21–4.14 (m, 4H), 4.05 (d, J = 8.4 Hz, 2H),
13C NMR (CDCl3, 100 MHz): δ 199.1, 168.0, 167.9, 137.1, 132.4, 4.02–3.98 (m, 4H), 1.24 (t, J = 7.6 Hz, 6H), 1.13 (t, J = 7.2 Hz,
130.8, 130.8, 126.9, 120.5, 53.1, 53.0, 51.3, 48.6. HRMS 6H); 13C NMR (CDCl3, 100 MHz): δ 198.3, 167.9, 167.6, 135.8,
(ESI-TOF) m/z: [M + H]+ calcd for C18H19ClO9: 415.0790; found: 135.2, 131.8, 130.6, 62.1, 61.8, 53.0, 43.5, 14.0, 13.9.
415.0793.
Tetraethyl 2-(2-chlorobenzoyl)propane-1,1,3,3-tetracarboxy-
Tetramethyl 2-(4-chlorobenzoyl)propane-1,1,3,3-tetracarboxy- late (3gb). Yellow oil (367 mg, 78%); 1H NMR (CDCl3,
late (3ha).4b Pale yellow oil (331 mg, 80%); 1H NMR (CDCl3, 400 MHz): δ 7.80–7.78 (m, 1H), 7.39–7.30 (m, 3H), 4.84 (t, J =
400 MHz): δ 7.97–7.95 (m, 2H), 7.46–7.44 (m, 2H), 4.80 (t, J = 7.2 Hz, 1H), 4.17–4.11 (m, 4H), 4.08–4.02 (m, 4H), 4.00 (d, J =
8.4 Hz, 1H), 4.09 (d, J = 8.0 Hz, 2H), 3.73 (s, 6H), 3.56 (s, 6H); 7.2 Hz, 2H), 1.25–1.21 (m, 12H); 13C NMR (CDCl3, 100 MHz):
13C NMR (CDCl3, 100 MHz): δ 198.0, 168.2, 168.0, 140.1, 134.9, δ 199.3, 167.6, 167.5, 137.5, 132.2, 130.9, 130.6, 129.6, 126.8,
130.5, 129.0, 53.2, 53.0, 52.5, 43.9.
Tetraethyl 2-benzoylpropane-1,1,3,3-tetracarboxylate (3ab).4b calcd for C22H27ClO9: 471.1416; found: 471.1415.
Pale yellow oil (375 mg, 86%); 1H NMR (CDCl3, 400 MHz):
Tetraethyl 2-(4-chlorobenzoyl)propane-1,1,3,3-tetracarboxy-
62.1, 51.8, 48.3, 14.0, 14.0. HRMS (ESI-TOF) m/z: [M + H]+
δ 8.03–8.01 (m, 2H), 7.57–7.53 (m, 1H), 7.47–7.43 (m, 2H), 4.86 late (3hb). Pale yellow oil (386 mg, 82%); 1H NMR (CDCl3,
(t, J = 8.0 Hz, 1H), 4.19–4.13 (m, 4H), 4.07 (d, J = 8.0 Hz, 2H), 400 MHz): δ 7.99–7.97 (m, 2H), 7.44–7.42 (m, 2H), 4.79 (t, J =
4.00–3.94 (m, 4H), 1.23 (t, J = 7.2 Hz, 6H), 1.11 (t, J = 7.2 Hz, 8.0 Hz, 1H), 4.20–4.16 (m, 4H), 4.05 (d, J = 8.0 Hz, 2H),
6H); 13C NMR (CDCl3, 100 MHz): δ 199.0, 167.9, 167.7, 136.9, 4.03–3.98 (m, 4H), 1.24 (t, J = 7.6 Hz, 6H), 1.13 (t, J = 7.2 Hz,
133.4, 129.1, 128.6, 62.0, 52.9, 43.8, 14.0, 13.8.
6H); 13C NMR (CDCl3, 100 MHz): δ 198.1, 167.9, 167.7, 139.9,
Tetraethyl 2-(2-methylbenzoyl)propane-1,1,3,3-tetracarboxy- 135.4, 130.5, 128.9, 62.2, 62.1, 53.1, 43.6, 14.0, 13.9. Anal. calcd
late (3bb). Yellow oil (364 mg, 81%); 1H NMR (CDCl3, for C22H27ClO9: C, 56.11; H, 5.78; found: C, 56.04; H, 5.70.
400 MHz): δ 7.88–7.86 (m, 1H), 7.37–7.35 (m, 1H), 7.24–7.20
Tetramethyl 2-(4-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
(m, 2H), 4.75 (t, J = 7.6 Hz, 1H), 4.09–4.02 (m, 8H), 4.00 (d, J = late (4aa).4b Pale yellow oil (315 mg, 80%); 1H NMR (CDCl3,
8.0 Hz, 2H), 2.45 (s, 3H), 1.24–1.16 (m, 12H); 13C NMR (CDCl3, 400 MHz): δ 7.92–7.90 (m, 2H), 7.28–7.25 (m, 2H), 4.85 (t, J =
100 MHz): δ 201.1, 167.7, 167.5, 139.3, 137.0, 131.6, 131.6, 8.8 Hz, 1H), 4.10 (d, J = 8.0 Hz, 2H), 3.72 (s, 6H), 3.53 (s, 6H),
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2.40 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 198.4, 168.3, 168.1,
144.6, 133.8, 129.4, 129.2, 53.0, 52.9, 52.4, 44.0, 21.8.
Tetraethyl 2-(4-methylbenzoyl)propane-1,1,3,3-tetracarboxy-
late (4ab). Pale yellow oil (364 mg, 81%); 1H NMR (CDCl3,
400 MHz): δ 7.93–7.91 (m, 2H), 7.26–7.24 (m, 2H), 4.84 (t, J =
8.0 Hz, 1H), 4.21–4.13 (m, 4H), 4.06 (d, J = 8.4 Hz, 2H),
4.02–3.93 (m, 4H), 2.39 (s, 3H), 1.23 (t, J = 7.2 Hz, 6H), 1.11 (t,
J = 7.2 Hz, 6H); 13C NMR (CDCl3, 100 MHz): δ 198.5, 168.0,
167.8, 144.4, 134.5, 129.3, 129.2, 62.0, 52.9, 43.6, 21.8, 14.0,
13.9. Anal. calcd for C23H30O9: C, 61.32; H, 6.71; found: C,
61.24; H, 6.67.
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4-Methyl-N-(2-oxo-2-phenylethyl)benzenesulfonamide (5a).11
White solid (248 mg, 86%); 1H NMR (CDCl3, 400 MHz):
δ 7.86–7.83 (m, 2H), 7.79–7.77 (m, 2H), 7.63–7.59 (m, 1H),
7.48–7.45 (m, 2H), 7.30–7.28 (m, 2H), 5.66 (t, J = 4.8 Hz, 1H),
4.46 (d, J = 4.4 Hz, 2H), 2.39 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 192.6, 143.9, 136.2, 134.5, 133.9, 129.9, 129.1,
128.0, 127.3, 48.8, 21.6.
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Conflicts of interest
There are no conflicts to declare.
8 G. Yuan, J. Zheng, X. Gao, X. Li, L. Huang, H. Chen and
H. Jiang, Chem. Commun., 2012, 48, 7513.
9 X. Ren, J. Chen, F. Chen and J. Cheng, Chem. Commun.,
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Acknowledgements
10 Z. Cao, H. Lv, Y. Liu, Z. Nie, H. Liu, T. Yang, W. Luo, Q. Liu
and C. Guo, Adv. Synth. Catal., 2019, 361, 1632.
11 S. Mahato, S. Santra, G. V. Zyryanov and A. Majee, J. Org.
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A. Majee acknowledges financial support from the CSIR-Major
Research Project (Ref. No. 02(0383)/19/EMR-II). S. Santra is
thankful to the Russian Science Foundation, Russia (Ref. # 18-
73-00301) for funding. We are thankful to the DST-FIST and
UGC-SAP program.
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