A novel acid-catalyzed rearrangement of 2-substituted-3-(2-nitrophenyl)oxiranes for the synthesis of di- and mono-oxalamides

Article abstract of DOI:10.1039/c6ra02586b

A novel one-pot synthetic approach to N¹-(2-carboxyaryl)-N²-(aryl or H)oxalamides from 3-(2-nitroaryl)oxirane-2-carboxamides via the classical Meinwald rearrangement and a new rearrangement sequence has been developed. The methodology is applicable to the synthesis of N-(2-carboxyphenyl)aryloxalmonoamides from (3-(2-nitrophenyl)oxiran-2-yl)(aryl)methanones. The method is operationally simple and high yielding, thus providing a new useful formula for both anthranilic acid derivatives and oxalamides.

Full text of DOI:10.1039/c6ra02586b

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L. Mamedova, G. Z. Khikmatova, E. V. Mironova, D. Krivolapov, O. B. Bazanova, D. V. Chachkov, S.
Katsyuba, I. Kh. Rizvanov and S. K. Latypov, RSC Adv., 2016, DOI: 10.1039/C6RA02586B.
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A novel acid-catalyzed rearrangement of 2-substituted-3-(2-
nitrophenyl)oxiranes for the synthesis of di- and mono-
oxalamides
Vakhid A. Mamedov,*,a,b Vera L. Mamedova,a,b Gul’nas Z. Khikmatova,b Ekaterina V.
Mironova,a Dmitry B. Krivolapov,a Olga B. Bazanova,a Denis V. Chachkov,b Sergey A.
Katsyuba,a Il’dar Kh. Rizvanova and Shamil K. Latypova
aA. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the
Russian Academy of Sciences, Arbuzov str. 8, 420088 Kazan, Russian Federation
bKazan National Research Technological University, Karl Marx str. 68, 420015 Kazan,
Russian Federation
mamedov@iopc.ru
ABSTRACT: A novel oneꢀpot synthetic approach to the N1ꢀ(2ꢀcarboxyaryl)ꢀN2ꢀ(aryl or
H)oxalamides from 3ꢀ(2ꢀnitroaryl)oxiraneꢀ2ꢀcarboxamides via the classical Meinwald
rearrangement and a new rearrangement sequence has been developed. The methodology is
applicable to synthesis of Nꢀ(2ꢀcarboxyphenyl)aryloxalmonoamides from (3ꢀ(2ꢀ
nitrophenyl)oxiranꢀ2ꢀyl)(aryl)methanones. The method is operationally simple and high yielding,
thus providing a new useful formula for both of anthranilic acid derivatives and oxalamides.
Introduction
Oxiranes are one of the most versatile classes of organic compounds available to the synthetic
chemist.1 They can be prepared by a wide variety of methods.2 One of the most frequently used
atom economical reactions of oxiranes is their rearrangement to carbonyl compounds, and a
number of reagents including a variety of Lewis acids3 have been elaborated for this purpose. In
principle, for trisubstituted оxiranes two types of rearrangements are possible depending on the
migration pathways following the Lewis acid promoted CꢀO bond cleavage (Scheme 1). The
rearrangement of I with hydride (path a) or the alkyl/aryl migration (path b) would lead to
ketone II or aldehyde III, respectively.3a,4 The synthetic applications of oxiranes have been the
subject of a number of reviews.1a,2,5

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Scheme 1 Possible rearrangements of the trisubstituted oxiranes.
The promise of increased chemoꢀ, regioꢀ, and stereoselectivity available via transition metal
catalysis6 has led investigators to study the interactions of oxiranes with transition metal
complexes, and a number of interesting and useful isomerization reactions have been reported.
Notably, oxiranes activated by adjacent aryl, vinyl, silyl, or carbonyl substituents are isomerized
to carbonyl compounds or allylic alcohols by complexes of Rh,7 Pd,8 Mo,9 Sm,10 Fe11 and In.12
Unlike all the considered reactions proceeding depending on the structure of oxirane and
applied conditions of rearrangement on the path a or b, our strategy included the use of oxiranes,
containing substituents with functional groups instead of the usual alkyl or aryl substituents.
These functional groups promote an intramolecular condensation (cyclization) of intermediate
ketone II or aldehyde III formed as a result of the above two transformations. Recently, our
group reported a novel metalꢀfree transannulation reaction of N,3ꢀdiaryloxiraneꢀ2ꢀcarboxamides
(AOСAs) involving a oneꢀpot acidꢀcatalyzed Meinwald rearrangement and intramolecular
FriedelꢀCrafts alkylation processes allowing to synthesize various 3ꢀarylquinolinꢀ2(1H)ꢀones in
high yields (Scheme 2).13 This novel approach features not only a metalꢀfree bond formation but
also an exclusive 1,2ꢀaryl migration.
Scheme 2 Our previous work and this work.
During our studies on the ringꢀopening/ringꢀclosure reactions of AOСAs, we attempted to
use Nꢀarylꢀ3ꢀ(2ꢀnitroaryl)oxiraneꢀ2ꢀcarboxamides (obtained from 2ꢀnitrobenzaldehydes and 2ꢀ
chloroꢀNꢀarylacetamides) with the aim of expanding the scope of the reaction. We found that
compounds with a newly formed oxalamide chain were obtained instead of expected 3ꢀ(2ꢀ
nitroaryl)quinolinꢀ2(1H)ones when the reactions were carried out in refluxing AcOH in the
presence of H2SO4. As far as we know, there has been no report on the synthesis of

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unsymmetrical oxalamides via the rearrangement yet. Herein, we report this novel acidꢀcatalyzed
rearrangement of AOCAs in AcOH, which proceeds through a cascade of the ringꢀopening/ringꢀ
closure/ringꢀclosure/ringꢀopening/ringꢀopening processes.
The salient features of our method are as follows: (1) a variety of aldehydes 1 and
chloroacetamides 2 are readily available and the rapid synthesis of 3 with diverse substitution
patterns are possible; (2) only two steps are necessary beginning with the starting materials to the
products 4; (3) the facile isolation of 3 and 4 are accomplished by a simple aqueous workup.
Results and discussion
The procedure of the Darzens condensation is the same as that described for AOСAs,13 except
that only 2ꢀnitrobenzaldehydes instead of variously substituted aromatic aldehydes with
chloroacetamides were used and the reactions were carried out at room temperature for 7 h. The
mixtures of cisꢀ and transꢀisomers of 3ꢀ(2ꢀnitroaryl)oxiraneꢀ2ꢀcarboxamides (3) with the
predominance of the transꢀisomer were easily purified from the cisꢀisomer by washing with ether
(Table 1).
Table 1 Synthesis of 3ꢀ(2ꢀnitroaryl)oxiranꢀ2ꢀcarboxamides
c
yieldtrans
%
,
entry
R1
H
H
H
2a
2a
2b
2c
R2
product
3ad
trans/cisb
1/0.12
1
1
2
3
Ph
87
85
76
1a
1a
1a
4ꢀBrC6H4
3ꢀMeC6H4
1/0.14
3b
1/0.19
3c
4
5
6
7
H
H
4ꢀMeOC6H4
3ꢀNO2C6H4
4ꢀCO2EtC6H4
Ph
1/0.29
1/0.07
1/0.09
1/0.30
62
91
89
61
1a
1a
1a
1b
2d
2e
2f
3d
3e
3f
H
Cl
2a
3g
8
H
H
1/0.00
100
1a
2g
3h
o
a2ꢀChloroꢀNꢀarylacetamides 2b-f were obtained on a 0.1 mol scale at 0ꢀ15 C by reacting
chloroacetylchloride with an equimolar amounts of corresponding aniline and Et3N. The
compounds 2a and 2g are commercially available.
bRatio was determined by 1H NMR оf the crude products.
cYields refer to isolated transꢀisomers of 3.
dcisꢀIsomer of this compound was obtained early.14
The structures of 3a-h were proved by variety of 1D/2D NMR correlation methods (see SI).15
First of all to clarify the optimal reaction conditions we examined the rearrangement of transꢀ3ꢀ
(2ꢀnitrophenyl)ꢀNꢀphenyloxiraneꢀ2ꢀcarboxamide (3a). After a brief survey of the reaction

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conditions, we have found that the product 4a is obtained in almost quantitative yield at reflux
for 3 h in AcOH with 1 equiv of H2SO4 (Table 2, entry 1).The reflux of 3a in both MeCN (with 1
equiv H2SO4) and AcOH for 3 h resulted in the mixtures containing 30 and 10% (determined by
1H NMR) of the desired product 4a, respectively. Further optimization of the reaction conditions
was carried out with transꢀ3ꢀ(2ꢀnitrophenyl)oxiraneꢀ2ꢀcarboxamide (3h). The reflux of 3h in
H2O with 1 equiv H2SO4 for 5 h or its storage at room temp in AcOH with 1 equiv of H2SO4 for
24 h gave 57 and 75% of the product 4h, respectively. However, an almost quantitative yield of
the rearrangement product was achieved when 1 equiv of H2SO4 was used in boiling AcOH for 3
h (entry 8). The latter condition was used for the rearrangement of all the compounds 3. The
rearrangement proceeds equally well with the compounds 3 containing various substituents in an
anilide moiety, no matter whether it is a strong electron donating (entry 4) or a strong electron
withdrawing (entry 5) group. Interestingly, under the rearrangement conditions the ester group
(entry 6) is not subjected to hydrolysis and it can be used in further transformations. The
presence of the chlorine atom with the –I and +M electronic effects in the aldehyde component
does not influence the yield of the rearrangement product (entry 7).
Table 2 Synthesis of Nꢀ(2ꢀcarboxyaryl)oxalamides
entry
R1
H
H
H
H
H
H
5ꢀCl
H
R2
Ph
product yield,a %
3
1
2
3
4
5
6
7
8
97
100
92
95
96
97
98
97
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
4ꢀBrC6H4
3ꢀMeC6H4
4ꢀMeOC6H4
3ꢀNO2C6H4
4ꢀCO2EtC6H4
Ph
3g
3h
4g
4h
H
aYields refer to isolated products.
To our delight 3ꢀ(2ꢀnitrophenyl)oxiraneꢀ2ꢀcarboxamides undergo the rearrangement with the
formation of compounds which can be considered both as anthranilic acid and as unsymmetrical
oxalamide derivatives. Anthranilic acid derivatives are potential anticancer agents16 and the
ligands for farnesoid X receptor.17 Oxalamides also represent a key framework of many bioactive
compounds.18 They have been developed as acetylcholine esterase inhibitors,19 C5a inhibitors,20
nitric oxide synthase inhibitors,21 antiꢀHIV agents,22 antiepileptic drugs,23 HIV integrase
inhibitors,24 HIVꢀ1 proteas inhibitors,25 cerpalosporin bactericides26 and chemioterapic agents.27
Considering the well documented medicinal utility of anthranilic acid and oxalamide derivatives,
these tethered combinations of the two scaffolds afford new opportunities to probe their
biological activity.
Based on above results and literature reports,3a,4,28aꢀc a plausible mechanism for the
rearrangement was proposed. First, the process was believed to proceed through the classical
Meinwald rearrangement (Scheme 1, path a) of 3ꢀ(2ꢀnitrophenyl)oxiraneꢀ2ꢀcarboxamides with
the cleavage of the C2ꢀO bond in its initial stage (3 → A). The resulting ketone A bearing an
active αꢀmethylene group undergoes a new rearrangement according to the mechanism of the
known BaeyerꢀDrewson indigo synthesis28aꢀc with the formation of intermediate C, which is

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further subjected to acidꢀcatalyzed ring opening (either C → D → E through pathway 1 or C →
I → J → F through pathway 2) involving hydration and dehydration processes (E → F → G →
H → 4 through pathway 1 and F → G → H → 4 through pathway 2) with the participation of
nitroꢀgroup and αꢀmethylene functionalities. As a result, the reduction of the nitroꢀgroup and the
transformation of the C3 atom of epoxide to the carboxylic functionality occurs (Scheme 3).
Pathway 2
4
Pathway 1
4
H
4
O
HN R2
1
R1
3
6
2
O
H
5
NO2
3
OH
H
R1
O
-H2O
N
O
O
G
O
H
O
R1
R2
N
H
HN
R2
H
+H2O
O
N
O
A
O
B
-H2O
OH
F
R1
H
O
O
OH
H
HO
O
R1
R2
N
N
H
R1
O
O
HO
O
H
N
O
N
HN
G
HN R2
R2
O
J
+H2O
+H2O
O
OH
O
R1
R1
R1
O
O
O
O
-H2O
N
N
O
HN R2
HN R2
N
O
HO
I
O
F
C
+H2O
HN
R2
OH
H
HO
O
R1
R1
O
O
O
N
HN R2
N
HN R2
O
O
HO
HO
D
E
Scheme 3 Proposed mechanisms of the rearrangement.
The structures of 4a-h were established unambiguously by various 1D/2D NMR correlation
methods.15 First, the proton spin systems of the Ar1 and Ar2 moieties were identified by
COSY/TOCSY methods. After that, the structures of both halves up to carbonyl groups (C1 and
1
C2) were established (boldfaced on Fig. 1) from the 1Hꢀ13C and Hꢀ15N HSQC/HMBC
connectivities. Finally, both halves were linked into a single whole on the basis of the NOEs
between protons of these two fragments:
Fig. 1 Structure of 4a with principal NMR correlations (1Hꢀ13C/15N HMBCs – black arrow,
NOEs – blue arrow).
Structures of the compounds 4a,b were further confirmed by singleꢀcrystal Xꢀray analyses
(Fig. 2).

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a
b
Fig. 2 ORTEP plot of compounds 4a (a) and 4b (b) partial numbering scheme. Displacement
ellipsoids are drawn at the 50% probability level. Hꢀatoms are represented in stick mode for
clarity.
It should be pointed out that a series of synthetic methods for oxalamides have been
described in the past decades.29 However, only five examples of the synthetic methods for
unsymmetrical oxalamides are known. The first is traditional and based on the condensation of
corresponding carboxylic acids with amines, which needs either activating agents or conversion
into more reactive derivatives.30 The next three methods include the direct amidation of
isocyanates,31 αꢀketo benzotriazole32 and trichloropyruvamides with amines.33 The fifth method
is a novel one and is based on green H2O2ꢀpromoted oxidative amidation of 2ꢀoxoaldehydes with
amines.34 Nevertheless, these methods have several drawbacks, such as harsh conditions,
expensive reagents, poor atomꢀefficiency and limited substrate scope. Method proposed in this
study demonstrated a new, efficient and metalꢀfree synthesis of unsymmetrical oxalamides via
novel rearrangement of easily available 3ꢀ(2ꢀnitroaryl)ꢀoxiraneꢀ2ꢀcarboxamides.
With this result in hand, we proceeded with the study of the scope of the rearrangement. As
can be seen from the suggested mechanism of the rearrangement (Scheme 3) the transformation
of 3ꢀ(2ꢀnitroaryl)oxiraneꢀ2ꢀcarboxamides to the oxalamides involves the 3ꢀ(2ꢀnitroaryl)oxirane
fragment only. Thus, seeking to expand accessible skeletal diversity using the same reaction
conditions, we anticipated that use of (3ꢀ(2ꢀnitroaryl)oxiranꢀ2ꢀyl)(aryl)methanones (6a-d) with
the same necessary fragment would facilitate access to 2ꢀ(2ꢀoxoꢀ2ꢀarylacetamido)benzoic acids
(7a-d). Indeed the refluxing of oxiranes 6a-d in AcOH in the presence of catalytic amount of
H2SO4 provides the desired monoꢀoxalamides 7a-d in good yields. Moreover, the reaction of 2ꢀ
nitrobenzaldehyde (1a) and 5ꢀchloroꢀ2ꢀnitrobenzaldehyde (1b) with 2ꢀchloroꢀ1ꢀ(4ꢀtolyl)ethanone
(5a), 2ꢀchloroꢀ1ꢀ(4ꢀmethoxyphenyl)ethanone (5b) and 2ꢀchloroꢀ1ꢀ(3ꢀnitrophenyl)ethanone (5c)
under the Darzens condensation condition proceeded smoothly, and (3ꢀ(2ꢀnitrophenyl)oxiranꢀ2ꢀ
yl)(aryl)methanones 6a-d were obtained in quantitative yields (Table 4). It should be pointed out
that in this case, in contrast to the reactions of chloroacetanilides 2,13 the process proceeds with
high stereoselectivity with the formation of only transꢀisomers of oxiranes 6a-d as the only
products.
Table 4 Synthesis of 2ꢀ(2ꢀoxoꢀ2ꢀphenylacetamido)benzoic acids 7a-d
OH
H
O
R2
O
R1
R1
O
R1
4
4
5
2
H2SO4 (cat)
AcOH, D, 3h
EtONa/EtOH
0.5 h, r.t.
3
3
6
O
O
Hal
+
H
R2
5a-c
5
NO2
NO2
NH
6
1
O
6a-d
1a,b
O
2
7a-d
R2
entry
R1 5a,b Hal
R2
product 6 product 7
yield,c %
1
1
2
3
H
H
H
Cl
4ꢀMeC6H4
75
81
86
1a
1a
1a
5a
5b
5c
6a
6b
6c
7a
7b
7c
Cl 4ꢀMeOC6H4
Br 3ꢀNO2C6H4

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4
Cl
Cl
4ꢀMeC6H4
89
1b
5a
6d
7d
a(Chloromethyl)arylketones 5a,b were obtained on a 0.1 mol scale at 10ꢀ20 oC by reaction of
1 equiv chloroacetilchloride with toluene (100 ml) and anisole (100 ml), respectively, with the
use of 1.5 equiv AlCl3.
o
b(Bromomethyl)arylketone 5c was obtained on a 0.1 mol scale at 50ꢀ55 C by reaction of 1
equiv 1ꢀ(3ꢀnitrophenyl)ethanone with 1 equiv bromine in ethanol (100 ml).
cYields refer to isolated products.
The structures of all compounds were proved by variety of 1D/2D NMR correlation methods
(see SI).15
Conclusion
In conclusion, we have discovered a new rearrangement of 3ꢀ(2ꢀnitrophenyl)ꢀoxiraneꢀ2ꢀ
carboxamides proceeding in boiling AcOH in the presence of H2SO4. The rearrangement
quantitatively produces the Nꢀ(2ꢀcarboxyaryl)oxalamides as a result of cascade processes
involving a) the classical Meinwald rearrangement in its initial stage with the formation of
ketone bearing an active αꢀmethylene group, b) transformation of carbonyl group of the ketone
to the carboxylic functionality, c) migration of active αꢀmethylene group to the nitrogen atom of
already reduced nitro group. The simple reaction conditions offer a potential for employing this
method in the synthesis of complex molecules. It is anticipated that this methodology will have
versatile applications in the practical syntheses of biologically important pharmaceutical
molecules with аnthranilic acid and oxalamide moieties. The methodology is applicable to
synthesis of Nꢀ(2ꢀcarboxyphenyl)aryloxalmonoamides from (3ꢀ(2ꢀnitrophenyl)oxiranꢀ2ꢀ
yl)(aryl)methanones. Further extension of the reaction scope and the synthetic applications of
this methodology are in progress at our laboratory.
Experimental section
General Methods. All reagents and solvents were used as purchased, without further
purification. Melting points were determined on a hotꢀstage apparatus. Infrared (IR) spectra
samples in Nujol were recorded on a FTꢀIR spectrometer Bruker Vectorꢀ22 in the 400–4000 cmꢀ1
range at optical resolution of 4 cmꢀ1. The high resolution MALDI massꢀspectra were obtained on
UltraFlex III TOF/TOF instrument in positive reflectron mode; 2,5ꢀDHB and pꢀNA were used as
matrix and PEGꢀ400 was used for calibration of accurate masses. All NMR experiments were
1
performed with 600, 500 and 400 MHz (600 MHz for H NMR; 150.9, 125 and 100.6 MHz for
13C NMR; 60.8 and 50.7 MHz for 15N NMR) spectrometers equipped with 5 mm diameter
gradient inverse broad band probehead and a pulsed gradient unit capable of producing magnetic
field pulse gradients in the zꢀdirection of 53.5 G·cmꢀ1. NMR experiments were carried out at 303
K. DPFGROE35 and TOCSY spectra were obtained using a Hermiteꢀshaped pulse for selective
excitation. Chemical shifts (δ in ppm) are referred to the solvent DMSOꢀd6 (δ = 2.49 ppm for 1H
and 39.5 ppm for 13C NMR), to external CD3NO2 (380.2 ppm) for 15N NMR spectra (conversion
factor to NH3: ꢀ380.2 ppm). 1Hꢀ1H coupling constants were computed according to
Bally&Rablen’s recommendations.36 First the geometry was optimized at the B3LYP/6ꢀ31G(d)
level. Then NMR singleꢀpoint calculation of the Fermi contact J values was run at the B3LYP/6ꢀ
31G(d,p) level. These values were scaled then by a factor of 0.9117. The quantum chemical
calculations were performed using a Gaussian 03 software package.37
General procedure for the Darzens condensation

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A solution of EtONa obtained when dissolving Na (0.73 g, 0.032 gꢀatom) in EtOH (20 ml)
was added at room temperature to the stirred solution of 2ꢀnitrobenzaldehyde (4.08 g, 0.027 mol)
with the corresponding compound 2 (0.027 mol) in EtOH (70 ml). The stirring is continued for 7
h. Treatment of the reaction mixtures as is usual for previous cases13 led to the products 3.
trans-3-(2-Nitrophenyl)-N-phenyloxirane-2-carboxamides (3a)
o
1
Tan powder (7.68 g, 0.027 mol, 87% yield): mp 180ꢀ181 C; H NMR (600 MHz, DMSOꢀd6)
δ
10.35 (s, 1H, NH), 8.20 (d, J = 8.2 Hz, 1H, H3ꢀAr1), 7.85 (dd, J = 7.6, 7.6 Hz, 1H, H5ꢀAr1),
7.65ꢀ7.69 (m, 3H, H2,6ꢀAr2; H4ꢀAr1), 7.59 (d, J = 7.9 Hz, 1H, H6ꢀAr1), 7.36 (dd, J = 7.9, 7.9
Hz, 2H, H3,5ꢀAr2), 7.12 (dd, J = 7.6, 7.2 Hz, 1H, H4ꢀAr2), 4.68 (d, J = 1.8 Hz, 1H, H3), 3.65 (d,
J = 1.8 Hz, 1H, H2); 13C NMR (150.9 MHz, DMSOꢀd6) δ 164.46 (C1), 147.46 (C2ꢀAr1), 138.23
(C1ꢀAr2), 134.66 (C5ꢀAr1), 132.19 (C1ꢀAr1), 129.50 (C4ꢀAr1), 128.78 (C3ꢀAr2), 126.73 (C6ꢀ
Ar1), 124.65 (C3ꢀAr1), 123.91 (C4ꢀAr2), 119.45 (C2ꢀAr2), 57.37 (C2), 55.14 (C3); 15N NMR
(60.8 MHz, DMSOꢀd6) δ 371.6 (NO2), 132.3 (NH); IR (nujol): υ 3279, 1674, 1604, 1553, 1525
cmꢀ1; HRMS (MALDI) calcd. for C15H12N2O4 [M+Cs]+ 416.9846, found 416.9843; Anal. Сalcd
for C15H12N2O4: C, 63.38; H, 4.25; N, 9.85; Found: C, 63.42; H, 4.13; N, 9.92.
trans-N-(4-Bromophenyl-3-(2-nitrophenyl)oxirane-2-carboxamide (3b)
Tan powder (8.33 g, 0.023 mol, 85% yield): mp 191ꢀ192 oC; 1H NMR (600 MHz, DMSOꢀd6):
δ
10.50 (s, 1H, NH), 8.19 (dd, J = 8.2, 1.0 Hz, 1H, H3ꢀAr1), 7.85 (dd, J = 7.7, 7.2 Hz, 1H, H5ꢀ
Ar1), 7.67 (ddd, J = 8.2, 7.7, 1.0 Hz, 1H, H4ꢀAr1), 7.64 (d, J = 8.7 Hz, 2H, H2,4ꢀAr2), 7.58 (d, J
= 7.7 Hz, 1H, H6ꢀAr1), 7.54 (d, J = 8.7 Hz, 2H, H3,5ꢀAr2), 4.68 (d, J = 1.8 Hz, 1H, H3), 3.64 (d,
J = 1.8 Hz, 1H, H2); 13C NMR (100.6 MHz, DMSOꢀd6) δ 164.74 (C1), 147.45 (C2ꢀAr1), 137.59
(C1ꢀAr2), 134.69 (C5ꢀAr1), 132.09 (C1ꢀAr1), 131.64 (C4ꢀAr2), 129.56 (C4ꢀAr1), 126.73 (C6ꢀ
Ar1), 124.68 (C3ꢀAr1), 121.43 (C2ꢀAr2), 115.61 (C4ꢀAr2), 57.36 (C2), 55.27 (C3); 15N NMR
(60.8 MHz, DMSOꢀd6) δ 371.5 (NO2), 131.2 (NH). IR (nujol): υ 3362, 1691, 1591, 1521 cmꢀ1;
HRMS (MALDI) calcd. for C15H11BrN2O4 [M+Cs]+ 494.8951;496.8932, found 494.8946;
496.8938; Anal. Calcd for C15H11BrN2O4: C, 49.61; H, 3.05; Br, 22.00; N, 7.71; Found: C,
49.84; H, 2.99; Br, 21.84; N, 7.87.
trans-3-(2-Nitrophenyl)-N-3-tolyloxirane-2-carboxamide (3c)
Tan powder (6.12 g, 0.021 mol, 76% yield): mp 140ꢀ143 oC; 1H NMR (600 MHz, DMSOꢀd6):
δ
10.29 (s, 1H, NH); 8.21 (dd, J = 8.2, 1.1 Hz, 1H, H3ꢀAr1), 7.86 (ddd, J = 7.5, 7.2, 1.1 Hz, 1H,
H5ꢀAr1), 7.68 (ddd, J = 7.9, 7.8, 1.4 Hz, 1H, H4ꢀAr1), 7.59 (d, J = 7.6 Hz, 1H, H2ꢀAr1), 7.51
(br.s, 1H, H2ꢀAr2), 7.45 (br.d, J = 8.2 Hz, 1H, H6ꢀAr2), 7.24 (dd, J = 7.8, 7.7 Hz, 1H, H5ꢀAr2),
6.94 (d, J = 7.4 Hz, 1H, H4ꢀAr2), 4.68 (d, J = 2.0 Hz, 1H, H3), 3.65 (d, J = 2.0 Hz, 1H, H2),
2.31 (s, 3H, CH3); 13C NMR (125.8 MHz, DMSOꢀd6) δ 164.39 (C1), 147.45 (C2ꢀAr1), 138.17
(C3ꢀAr2), 138.05 (C1ꢀAr2), 134.69 (C5ꢀAr1), 132.24 (C1ꢀAr1), 129.51 (C4ꢀAr1), 128.64 (C5ꢀ

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Ar2), 126.73 (C6ꢀAr1), 124.67 (C4ꢀAr2), 124.62 (C3ꢀAr1), 119.96 (C2ꢀAr2), 116.65 (C6ꢀAr2),
57.38 (C2), 55.14 (C3), 21.09 (Me); 15N NMR (60.8 MHz, DMSOꢀd6) δ 371.6 (NO2), 132.5
(NH); IR (nujol): υ 3252, 1667, 1611, 1556, 1524 cmꢀ1; HRMS (MALDI) calcd. for C16H14N2O4
[M+Cs]+ 431.0003, found 430.9994; Anal. Calcd for C16H14N2O4: C, 64.42; H, 4.73; N, 9.39;
Found: C, 64.86; H, 4.72; N, 9.41.
trans-N-(4-Methoxyphenyl)-3-(2-nitrophenyl)oxirane-2-carboxamide (3d)
Brown powder (5.34 g, 0.017 mol, 62% yield): mp 168ꢀ169 oC; 1H NMR (600 MHz, DMSOꢀd6):
δ
10.23 (s, 1H, NH), 8.21 (dd, J = 8.2, 1.1 Hz, 1H, H3ꢀAr1), 7.86 (ddd, J = 7.6, 7.6, 1.0 Hz, 1H,
H5ꢀAr1), 7.68 (ddd, J = 7.8, 7.8, 1.3 Hz, 1H, H4ꢀAr1), 7.49ꢀ7.60 (m, 3H, H2,4ꢀAr2;H6ꢀAr1),
6.93 (d, J = 9.1 Hz, 2H, H3,5ꢀAr2), 4.68 (d, J = 1.9 Hz, 1H, H3), 3.75 (s, 3H, OCH3), 3.61 (d, J
= 1.9 Hz, 1H, H2); 13C NMR (125.8 MHz, DMSOꢀd6) δ 163.98 (C1), 155.67 (C4ꢀAr2), 147.47
(C2ꢀAr1), 134.69 (C5ꢀAr1), 132.28 (C1ꢀAr1), 131.40 (C1ꢀAr2), 129.51 (C4ꢀAr1), 126.75 (C6ꢀ
Ar1), 124.68 (C3ꢀAr1), 121.10 (C2ꢀAr2), 113.94 (C3ꢀAr2), 57.44 (C2), 55.17 (OMe), 55.10
(C3); 15N NMR (60.8 MHz, DMSOꢀd6) δ 371.8 (NO2ꢀAr1), 130.6 (NH); IR (nujol): υ 3268,
1664, 1608, 1556, 1514 cmꢀ1; HRMS (MALDI) calcd. for C16H14N2O5 [M+Na]+ 337.0795, found
337.0814; Anal. Calcd for C16H14N2O5: C, 61.14; H, 4.50; N, 8.91. Found: C, 61.53; H, 4.48; N,
8.93.
trans-N-(3-Nitrophenyl)-3-(2-nitrophenyl)oxirane-2-carboxamide (3e)
o
1
Tan powder (8.09 g, 0.025 mol, 91% yield): mp 177 C; H NMR (600 MHz, DMSOꢀd6):
δ
10.83 (s, 1H, NH), 8.70 (dd, J = 2.2, 2.2 Hz, 1H, H2ꢀAr2), 8.21 (dd, J = 8.3, 1.0 Hz, 1H, H3ꢀ
Ar1), 8.01 (dd, J = 8.2, 1.5 Hz, 1H, H6ꢀAr2), 7.98 (dd, J = 8.2, 1.3 Hz, 1H, H4ꢀAr2), 7.86 (dd, J
= 7.7, 7.3 Hz, 1H, H5ꢀAr1), 7.68 (dd, J = 7.7, 1.4 Hz, 1H, H4ꢀAr1), 7.66 (dd, J = 8.2, 8.2 Hz,
1H, H5ꢀAr2), 7.60 (d, J = 7.7 Hz, 1H, H6ꢀAr1), 4.73 (d, J = 2.0 Hz, 1H, H3), 3.70 (d, J = 2.0 Hz,
1H, H2); 13C NMR (150.9 MHz, DMSOꢀd6) δ 165.44 (C1), 147.95 (C3ꢀAr2), 147.44 (C2ꢀAr1),
139.27 (C1ꢀAr2), 134.70 (C5ꢀAr1), 131.90 (C1ꢀAr1), 130.29 (C5ꢀAr2), 129.62 (C4ꢀAr1), 126.76
(C6ꢀAr1), 125.50 (C6ꢀAr2), 124.68 (C3ꢀAr1), 118.47 (C4ꢀAr2), 113.72 (C2ꢀAr2), 57.26 (C2),
55.48 (C3); 15N NMR (60.8 MHz, DMSOꢀd6) δ 371.4 (NO2ꢀAr1), 370.3 (NO2ꢀAr2), 130.7 (NH);
IR (nujol): υ 3241, 1673, 1535, 1522 cmꢀ1; HRMS (MALDI) calcd. for C15H11N3O6 [M+Na]+
352.0540, found 352.0559; Anal. Calcd for C15H11N3O6: C, 54.72; H, 3.37; N, 12.76. Found: C,
54.69; H, 3.28; N, 12.78.
trans-3-(2-Nitrophenyl)-N-(4-ethylcarboxyphenyl)oxirane-2-carboxamide (3f)
o
1
White powder (8.56 g, 0.024 mol, 89% yield): mp 180ꢀ182 C; H NMR (600 MHz, DMSOꢀd6)
10.86 (br.s, 1H, NH), 8.21 (d, J = 8.2 Hz, 1H, H3ꢀAr1), 7.96 (d, J = 8.5 Hz, 2H, H3,5ꢀAr2),
δ
7.86 (dd, J = 7.6, 7.6 Hz, 1H, H5ꢀAr1), 7.83 (d, J = 8.5 Hz, 2H, H2,6ꢀAr2), 7.68 (dd, J = 8.0, 7.7
Hz, 1H, H4ꢀAr1), 7.59 (d, J = 7.2 Hz, 1H, H6ꢀAr1), 4.71 (d, J = 1.7 Hz, 1H, H3), 3.75 (d, J = 1.7

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Hz, 1H, H2), 4.30 (q, J = 7.1 Hz, 2H, OCH2CH3), 1.33 (t, J = 7.1 Hz, 3H, OCH2CH3); 13C NMR
(125.8 MHz, DMSOꢀd6) δ 165.21 (CO2Et), 165.17 (C1), 147.46 (C2ꢀAr1), 142.57 (C1ꢀAr2),
134.72 (C5ꢀAr1), 132.11 (C1ꢀAr1), 130.24 (C3ꢀAr2), 129.59 (C4ꢀAr1), 126.78 (C6ꢀAr1), 124.93
(C4ꢀAr2), 124.70 (C3ꢀAr1), 118.94 (C2ꢀAr2), 60.46 (OCH2CH3), 57.28 (C2), 55.37 (C3), 14.15
(OCH2CH3); 15N NMR (60.8 MHz, DMSOꢀd6) δ 371.7 (NO2), 134.1 (NH); IR (nujol): υ 3360,
1711,1697, 1608, 1595, 1522 смꢀ1; HRMS (MALDI) calcd. for C18H16N2O6 [M+Cs]+ 489.0057,
found 489.0055; Anal. Calcd for C18H16N2O6: C, 60.67; H, 4.53; N, 7.86. Found: C, 60.68; H,
4.48; N, 7.93.
trans-3-(2-Nitro-5-chlorophenyl)-N-phenyloxirane-2-carboxamide (3g)
o
1
White powder (5.25 g, 0.016 mol, 61% yield): mp 156ꢀ158 C; H NMR (600 MHz, DMSOꢀd6)
10.38 (s, 1H, NH), 8.25 (d, J = 8.8 Hz, 1H, H3ꢀAr1), 7.75 (dd, J = 8.8, 2.4 Hz, 1H, H4ꢀAr1),
δ
7.67 (d, J = 8.4 Hz, 2H, H2,6ꢀAr2), 7.56 (d, J = 2.4 Hz, 1H, H6ꢀAr1), 7.38 (dd, J = 8.4, 7.5 Hz,
2H, H3,5ꢀAr2), 7.13 (ddd, J = 7.5, 7.4, 1.0 Hz, 1H, H4ꢀAr2), 4.72 (d, J = 2.0 Hz, 1H, H3), 3.72
13
(d, J = 2.0 Hz, 1H, H2); C NMR (125.8 MHz, DMSOꢀd6) δ 164.23 (C1), 146.12 (C2ꢀAr1),
139.53 (C5ꢀAr1), 138.19 (C1ꢀAr2), 134.65 (C1ꢀAr1), 129.46 (C4ꢀAr1), 128.82 (C3ꢀAr2), 126.90
(C3ꢀAr1), 126.53 (C6ꢀAr1), 123.99 (C4ꢀAr2), 119.50 (C2ꢀAr2), 57.34 (C2), 54.84 (C3); 15N
NMR (60.8 MHz, DMSOꢀd6) δ 368.9 (NO2), 132.6 (NH); IR (nujol): υ 3368, 1693, 1600, 1571,
1533 cmꢀ1; HRMS (MALDI) calcd. for C15H11ClN2O4 [M+Na]+ 341.0299, found 341.0308;
Anal. Calcd for C15H11ClN2O4: C, 56.53; H, 3.48; Cl, 11.12; N, 8.79. Found: C, 56.62; H, 3.32;
Cl, 11.18; N, 8.92.
trans-3-(2-Nitrophenyl)oxirane-2-carboxamide (3h)
o
1
Light yellow powder (5.62 g, 0.027 mol, 100% yield): mp 209ꢀ210 C; H NMR (600 MHz,
DMSOꢀd6) 8.18 (dd, J = 8.1, 1.0 Hz, 1H, H3ꢀAr1), 7.82 (ddd, J = 7.8, 7.8, 1.0 Hz, 1H, H5ꢀ
δ
Ar1), 7.69 (br.s, 1H, NH2); 7.65 (ddd, J = 8.1, 7.8, 1.2 Hz, 1H, H4ꢀAr1), 7.48 (br.s, 1H,
NH2);7.53 (d, J = 7.7 Hz, 1H, H6ꢀAr1), 4.52 (d, J = 1.9 Hz, 1H, H3), 3.39 (d, J = 1.9 Hz, 1H,
H2); 13C NMR (125.8 MHz, DMSOꢀd6) δ 168.07 (C1), 147.50 (C2ꢀAr), 134.68 (C5ꢀAr), 132.43
(C1ꢀAr), 129.46 (C4ꢀAr), 126.73 (C6ꢀAr), 124.68 (C3ꢀAr), 57.05 (C2), 54.91 (C3); 15N NMR
(50.7 MHz, DMSOꢀd6) δ 371.8 (NO2), 106.4 (NH2); IR (nujol): υ 3368, 3185, 1665, 1526 cmꢀ1;
HRMS (MALDI) calcd. for C9H8N2O4 [M+Cs]+ 340.9533, found 340.9536; Anal. Calcd for
C9H8N2O4: C, 51.93; H, 3.87; N, 13.46. Found: C, 52.02; H, 3.85; N, 13.43.
General procedure for the rearrangement
Concd H2SO4 (0.1 ml) was added to the solution of 3 (1.67 mmol) in AcOH (5 ml). The
reaction mixture was boiled for 3 h and then poured into water. The precipitate thus formed was
collected by filtration, washed with water and dried.
N1-(2-carboxyphenyl)-N2-phenyloxalamide (4a)

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o
1
Light brown powder (0.46 g, 1.62 mmol, 97% yield): mp 227ꢀ228 C; H NMR (600 MHz,
DMSOꢀd6) 12.75 (s, 1H, N1H), 10.89 (s, 1H, N2H), 8.70 (ddd, J = 8.3, 8.3, 1.0 Hz, 1H, H3ꢀ
δ
Ar1), 8.08 (dd, J = 8.0, 1.5 Hz, 1H, H6ꢀAr1), 7.88 (dd, J = 8.7, 1.1 Hz, 2H, H2,6ꢀAr2), 7.71
(ddd, J = 7.9, 7.9, 1.7 Hz, 1H, H4ꢀAr1), 7.39 (ddd, J = 8.7, 7.6, 1.1 Hz, 2H, H3,5ꢀAr2), 7.29
13
(ddd, J = 7.6, 7.6, 1.1 Hz, 1H, H5ꢀAr1), 7.18 (ddd, J = 7.4, 7.4, 1.0 Hz, 1H, H4ꢀAr2); C NMR
(125.8 MHz, DMSOꢀd6) δ 168.84 (CO2H), 158.29 (2C=O), 158.03 (1C=O), 139.16 (C2ꢀAr1),
137.41 (C1ꢀAr2), 134.19 (C4ꢀAr1), 131.43 (C6ꢀAr1), 128.65 (C3ꢀAr2), 124.72 (C4ꢀAr2), 123.92
(C5ꢀAr1), 120.60 (C2ꢀAr2), 119.53 (C3ꢀAr1), 117.39 (C1ꢀAr1); 15N NMR (60.8 MHz, DMSOꢀ
d6) δ 126.8 (N2), 121.7 (N1); IR (nujol): υ 3329, 3179, 1678, 1586, 1520 cmꢀ1; HRMS (MALDI)
calcd. for C15H12N2O4 [M+Na]+ 307.0689, found 307.0690; Anal. Calcd for C15H12N2O4: C,
63.38; H, 4.25; N, 9.85. Found: C, 63.34; H, 4.31; N, 9.93.
N1-(2-carboxyphenyl)-N2-(4-bromophenyl)oxalamide (4b)
o
Grey powder (0.61 g, 1.67 mmol, 100% yield): mp 281ꢀ283 C; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.72 (s, 1H, N1H), 11.04 (s, 1H, N2H), 8.68 (d, J = 8.2 Hz, 1H, H3ꢀAr1), 8.07 (dd, J = 8.2,
1.5 Hz, 1H, H6ꢀAr1), 7.85 (d, J = 8.7 Hz, 2H, H2,6ꢀAr2), 7.71 (ddd, J = 7.9, 7.7, 1.5 Hz, 1H,
H4ꢀAr1), 7.57 (d, J = 8.7 Hz, 2H, H3,5ꢀAr2), 7.28 (ddd, J = 7.7, 7.7, 1.0 Hz, 1H, H5ꢀAr1); 13C
NMR (150.9 MHz, DMSOꢀd6) δ 168.82 (CO2H), 158.18 (2C=O), 158.03 (1C=O), 139.10 (C2ꢀ
Ar1), 136.84 (C1ꢀAr2), 134.20 (C4ꢀAr1), 131.49 (C3ꢀAr2), 131.41 (C6ꢀAr1), 123.95 (C5ꢀAr1),
122.54 (C2ꢀAr2), 119.54 (C3ꢀAr1), 117.32 (C1ꢀAr1), 116.65 (C4ꢀAr2); 15N NMR (60.8 MHz,
DMSOꢀd6) δ 126.6 (N2), 122.2 (N1); IR (nujol): υ 3301, 3189, 1687, 1584, 1519 cmꢀ1; HRMS
(MALDI) calcd. for C15H11BrN2O4 [M+Na]+ 384.9794;386.9776, found 384.9795;386.9786;
Anal. Calcd for C15H11BrN2O4: C, 49.61; H, 3.05; Br, 22.00; N, 7.71. Found: C, 49.38; H, 3.02;
Br, 22.07; N, 7.69.
]N1-(2-carboxyphenyl)-N2-(3-methylphenyl)oxalamide (4c)
Brown powder (0.46 g, 1.54 mmol, 92% yield): mp 203ꢀ205 oC; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.72 (s, 1H, N1H), 10.79 (s, 1H, N2H), 8.70 (d, J = 8.4, 1.0 Hz, 1H, H3ꢀAr1), 8.08 (dd, J =
7.9, 1.6 Hz, 1H, H6ꢀAr1), 7.73 (br.s, 1H, H2ꢀAr2), 7.72 (ddd, J = 7.8, 7.8, 1.7 Hz, 1H, H4ꢀAr1),
7.64 (br.d, J = 8.3 Hz, 1H, H6ꢀAr1), 7.29 (ddd, J = 7.9, 7.9, 1.2 Hz, 1H, H5ꢀAr1), 7.27 (dd, J =
7.8, 7.8 Hz, 1H, H5ꢀAr2), 7.00 (d, J = 7.6 Hz, 1H, H4ꢀAr2), 2.33 (s, 3H, CH3); 13C NMR (125.8
MHz, DMSOꢀd6) δ 168.83 (CO2H), 158.32 (2C=O), 157.95 (1C=O), 139.16 (C2ꢀAr1), 137.92
(C3ꢀAr2), 137.31 (C1ꢀAr2), 134.24 (C4ꢀAr1), 131.44 (C6ꢀAr1), 128.50 (C5ꢀAr2), 125.44 (C4ꢀ
Ar2), 123.94 (C5ꢀAr1), 121.06 (C2ꢀAr2), 119.53 (C3ꢀAr1), 117.82 (C6ꢀAr2), 117.31 (C1ꢀAr1),
21.12 (Me); 15N NMR (50.7 MHz, DMSOꢀd6) δ 126.9 (N2), 121.8 (N1); IR υ (nujol): υ 3317,
3187, 1678, 1587, 1528 cmꢀ1; HRMS (MALDI) calcd. for C16H14N2O4 [M+Cs]+ 431.0003,
found 431.0014; Anal. Calcd for C16H14N2O4: C, 64.42; H, 4.73; N, 9.39. Found: C, 64.31; H,
4.68; N, 9.42.
N1-(2-carboxyphenyl)-N2-(4-methoxyphenyl)oxalamide (4d)

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Grey powder (0.50 g, 1.59 mmol, 95% yield): mp 272ꢀ273 oC; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.70 (s, 1H, N1H), 10.78 (s, 1H, N2H), 8.69 (ddd, J = 8.4, 7.7, 1.0 Hz, 1H, H3ꢀAr1), 8.07 (dd, J
= 8.2, 1.6 Hz, 1H, H6ꢀAr1), 7.78 (d, J = 9.1 Hz, 2H, H2,6ꢀAr2), 7.71 (ddd, J = 7.9, 7.8, 1.6 Hz,
1H, H4ꢀAr1), 7.28 (ddd, J = 7.8, 7.4, 1.1 Hz, 1H, H5ꢀAr1), 6.95 (d, J = 9.1 Hz, 2H, H3,5ꢀAr2),
3.76 (s, 3H, OCH3); 13C NMR (125.8 MHz, DMSOꢀd6) δ 168.91 (CO2H), 158.56 (2C=O),
157.66 (1C=O), 156.34 (C4ꢀAr2), 139.24 (C2ꢀAr1), 134.31 (C4ꢀAr1), 131.51 (C6ꢀAr1), 130.54
(C1ꢀAr2), 124.01 (C5ꢀAr1), 122.15 (C2ꢀAr2), 119.63 (C3ꢀAr1), 117.37 (C1ꢀAr1), 113.91 (C3ꢀ
Ar2), 55.27 (OMe); 15N NMR (50.7 MHz, DMSOꢀd6) δ 125.6 (N2), 121.8 (N1); IR (nujol): υ
3336, 3218, 1683, 1585, 1525 cmꢀ1; HRMS (MALDI) calcd. for C16H14N2O5 [M+Cs]+ 446.9952,
found 446.9953; Anal. Calcd for C16H14N2O5: C, 61.14; H, 4.50; N, 8.91. Found: C, 60.99; H,
4.58; N, 8.97.
N1-(2-carboxyphenyl)-N2-(3-nitrophenyl)oxalamide (4e)
Brown powder (0.53, 1.61 mmol, 96% yield): mp 254ꢀ256 oС; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.90 (s, 1H, N1H), 11.40 (s, 1H, N2H), 8.90 (dd, J = 2.0, 2.0 Hz, 1H, H2ꢀAr2), 8.69 (d, J = 8.2
Hz, 1H, H3ꢀAr1), 8.27 (dd, J = 7.9, 1.2 Hz, 1H, H6ꢀAr2), 8.08 (dd, J = 7.9, 1.2 Hz, 1H, H6ꢀAr1),
8.02 (dd, J = 7.9, 1.8 Hz, 1H, H4ꢀAr2), 7.66ꢀ7.72 (m, 2H, H5ꢀAr2; H4ꢀAr1), 7.28 (dd, J = 7.8,
7.2 Hz, 1H, H5ꢀAr1); 13C NMR (150.9 MHz, DMSOꢀd6) δ 168.93 (CO2H), 158.76 (2C=O),
157.68 (1C=O), 147.87 (C3ꢀAr2), 139.05 (C2ꢀAr1), 138.71 (C1ꢀAr2), 134.02 (C4ꢀAr1), 131.43
(C6ꢀAr1), 130.09 (C5ꢀAr2), 126.68 (C6ꢀAr2), 123.97 (C5ꢀAr1), 119.51 (C3ꢀAr2), 119.17 (C4ꢀ
Ar2), 117.80 (C1ꢀAr1), 114.81 (C2ꢀAr2);15N NMR (60.8 MHz, DMSOꢀd6) δ 370.1 (NO2), 126.6
(N2), 122.2 (N1); IR (nujol): υ 3326, 3188, 1690, 1589, 1532 cmꢀ1; HRMS (MALDI) calcd. for
C15H11N3O6 [M+Na]+ 352.0540, found 352.0563; Anal. Calcd for C15H11N3O6: C, 54.72; H,
3.37; N, 12.76. Found: C, 54.82; H, 3.43; N, 12.68.
N1-(2-carboxyphenyl)-N2-(4-ethylcarboxypheny)oxalamide (4f)
o
1
Light green powder (0,58 g, 1.63 mmol, 97% yield): mp 268ꢀ269 C; H NMR (600 MHz,
DMSOꢀd6) 12.78 (s, 1H, N1H), 11.18 (s, 1H, N2H), 8.68 (d, J = 8.8 Hz, 1H, H3ꢀAr1), 8.08 (d,
δ
J = 7.7 Hz, 1H, H6ꢀAr1), 8.04 (d, J = 8.8 Hz, 2H, H2,6ꢀAr2), 7.96 (d, J = 8.8 Hz, 2H, H3,5ꢀAr2),
7.70 (dd, J = 7.7, 7.7 Hz, 1H, H4ꢀAr1), 7.28 (dd, J = 7.7, 7.7 Hz, 1H, H5ꢀAr1), 4.30 (q, J = 7.1
Hz, 2H, OCH2CH3), 1.32 (t, J = 7.1 Hz, 3H, OCH2CH3); 13C NMR (150.9 MHz, DMSOꢀd6) δ
168.90 (CO2H), 165.18 (CO2Et), 158.52 (2C=O), 157.88 (1C=O), 141.74 (C1ꢀAr2), 139.12 (C2ꢀ
Ar1), 134.17 (C4ꢀAr1), 131.45 (C6ꢀAr1), 129.94 (C3ꢀAr2), 125.70 (C4ꢀAr2), 123.97 (C5ꢀAr1),
120.12 (C2ꢀAr2), 119.53 (C3ꢀAr1), 117.47 (C1ꢀAr1), 60.52 (OCH2CH3), 14.13 (OCH2CH3); 15N
NMR (60.8 MHz, DMSOꢀd6) δ 127.6 (N2), 122.0 (N1); IR (nujol): υ 3355, 3260, 1708, 1688,
1602, 1586, 1524, 1271, 761 cmꢀ1; HRMS (MALDI) calcd. for C18H16N2O6 [M+2CsꢀH]+

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620.9034, found 620.9042; Anal. Calcd for C18H16N2O6: C, 60.67; H, 4.53; N, 7.86. Found: C,
60.59; H, 4.48; N, 7.97.
N1-(4-chloro-2-carboxyphenyl)-N2-phenyloxalamide (4g)
Brown powder (0.52 g, 1.63 mmol, 98% yield): mp 242ꢀ243 oC; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.84 (s, 1H, N1H), 10.89 (s, 1H, N2H), 8.70 (d, J = 8.9 Hz, 1H, H3ꢀAr1), 8.02 (d, J = 2.6 Hz,
1H, H6ꢀAr1), 7.86 (d, J = 7.8 Hz, 2H, H2,6ꢀAr2), 7.76 (dd, J = 8.9, 2,6 Hz, 1H, H4ꢀAr1), 7.39
(dd, J = 8.1, 7.5 Hz, 2H, H3,5ꢀAr2), 7.18 (dd, J = 7.5, 7.4 Hz, 1H, H4ꢀAr2); 13C NMR (100.9
MHz, DMSOꢀd6) δ 167.59 (CO2H), 158.34 (2C=O), 157.86 (1C=O), 137.98 (C2ꢀAr1), 137.37
(C1ꢀAr2), 133.58 (C4ꢀAr1), 130.61 (C6ꢀAr1), 128.64 (C3ꢀAr2), 127.51 (C5ꢀAr1), 124.74 (C4ꢀ
Ar2), 121.29 (C3ꢀAr1), 120.61 (C2ꢀAr2), 119.71 (C1ꢀAr1); 15N NMR (50.7 MHz, DMSOꢀd6) δ
127.0 (N2), 121.4 (N1); IR (nujol): υ 3331, 3166, 1679, 1579, 1505 cmꢀ1; HRMS (MALDI)
calcd. for C15H11ClN2O4 [M+Na]+ 341.0300, found 341.0328; Anal. Calcd for C15H11ClN2O4: C,
56.53; H, 3.48; Cl, 11.12; N, 8.79. Found: C, 56.59; H, 3.52; Cl, 11.07; N, 8.99.
N-(2-carboxyphenyl)oxalamide (4h)
Violet powder (0.34 g, 1.62 mmol, 97% yield): mp 267ꢀ268 0C; 1H NMR (600 MHz, DMSOꢀd6)
δ
12.51 (s, 1H, N1H), 8.65 (d, J = 8.2 Hz, 1H, H3ꢀAr), 8.36 (br.s, 1H, NH2), 8.05 (br.s, 1H,
NH2), 8.04 (dd, J = 8.0, 1.6 Hz, 1H, H6ꢀAr), 7.68 (ddd, J = 7.9, 7.9, 1.5 Hz, 1H, H4ꢀAr), 7.25
(ddd, J = 7.6, 7.6, 1.0 Hz, 1H, H5ꢀAr); 13C NMR (125.8 MHz, DMSOꢀd6) δ 168.66 (CO2H),
161.57 (1C=O), 158.73 (2C=O), 139.19 (C2ꢀAr), 134.13 (C4ꢀAr), 131.38 (C6ꢀAr), 123.70 (C5ꢀ
Ar), 119.47 (C3ꢀAr), 117.22 (C1ꢀAr); 15N NMR (50.7 MHz, DMSOꢀd6) δ 103.5 (N2), 121.3
(N1); IR (nujol): υ 3538, 3465, 3321, 3168, 1729, 1683, 1592, 1537, 1272, 752 cmꢀ1; HRMS
(MALDI) calcd. for C9H8N2O4 [M+2CsꢀH]+ 472.8509, found 472.8491; Anal. Calcd for
C9H8N2O4: C, 51.93; H, 3.87; N, 13.46. Found: C, 51.90; H, 3.89; N, 13.42.
Synthesis of (3-(2-nitroaryl)oxiran-2-yl)(aryl)methanones (6a-d) was performed according to
the general procedure for the Darzens condensation with the use of corresponding
(halomethyl)arylketones (5a-c) instead of chloroacetamides (2a-g). In these cases as distinct
from the synthesis of 3ꢀ(2ꢀnitroaryl)oxiranꢀ2ꢀcarboxamides (3a-h) the reactions are completed
for 0.5 h. The products precipitated during the reaction and did not require any purification
except washing with water (3×25mL).
trans-(3-(2-Nitrophenyl)oxiran-2-yl)(4-tolyl)methanone (6a)
o
1
White powder (7.65 g, 0.027 mol, 100% yield): mp 154 C; H NMR (400 MHz, DMSOꢀd6)
δ
8.21 (dd, J = 8.1, 1.0 Hz, 1H, H3ꢀAr1), 8.0 (d, J = 8.2 Hz, 2H, H3,5ꢀAr2), 7.88 (ddd, J = 7.6, 7.5,
0.8 Hz, 1H, H5ꢀAr1), 7.65ꢀ7.71 (m, 2H, H4,6ꢀAr1), 7.37 (d, J = 8.2 Hz, 2H, H2,6ꢀAr1), 4.74 (d,
J = 2.1 Hz, 1H, H2), 4.56 (d, J = 2.1 Hz, 1H, H3), 2.41 (s, 3H, Me); 13C NMR (100.6 MHz,

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DMSOꢀd6) δ 192.14 (1C=O), 147.47 (C2ꢀAr1), 144.72 (C4ꢀAr2), 134.60 (C5ꢀAr1), 132.70 (C1ꢀ
Ar2), 132.42 (C1ꢀAr1), 129.47 (C4ꢀAr1), 129.38 (C2ꢀAr2), 128.50 (C3ꢀAr2), 127.02 (C6ꢀAr1),
124.62 (C3ꢀAr1), 58.34 (C2), 57.15 (C3), 21.19 (Me). IR (nujol):
ν
1682, 1522 cmꢀ1; HRMS
(MALDI) calcd. for C16H13NO4 [M+Cs]+ 415.9894, found 415.9895; Anal. Сalcd for
C16H13NO4: C, 67.84; H, 4.63; N, 4.94; Found: C, 67.89; H, 4.62; N, 4.98.
trans-(4-Methoxyphenyl)(3-(2-nitrophenyl)oxiran-2-yl)methanone (6b)
o
1
White powder (8.08 g, 0.027 mol, 100% yield): mp 141 C; H NMR (400 MHz, DMSOꢀd6)
δ
8.21 (d, J = 8.2 Hz, 1H, H3ꢀAr1), 8.09 (d, J = 8.1 Hz, 2H, H2,6ꢀAr2), 7.87 (dd, J = 7.6, 7.4 Hz,
1H, H5ꢀAr1), 7.65ꢀ7.71 (m, 2H, H6,4ꢀAr1), 7.08 (d, J = 8.1 Hz, 2H, H3,5ꢀAr2), 4.71 (d, J = 1.7
Hz, 1H, H2), 4.56 (d, J = 1.7 Hz, 1H, H3), 3.87 (s, 3H, OMe); 13C NMR (125.8 MHz, DMSOꢀd6)
δ 190.82 (1C=O), 163.87 (C4ꢀAr2), 147.45 (C2ꢀAr1), 134.60 (C5ꢀAr1), 132.53 (C1ꢀAr1), 130.87
(C2ꢀAr2), 129.43 (C4ꢀAr1), 128.20 (C1ꢀAr2), 127.05 (C6ꢀAr1), 124.61 (C3ꢀAr1), 114.11 (C3ꢀ
Ar2), 58.17 (C2), 57.03 (C3), 55.58 (OMe). IR (nujol):
ν 1678, 1597, 1513; HRMS (MALDI)
calcd. for C16H13NO5 [M+Cs]+ 431.9843, found 431.9813; Anal. Сalcd for C16H13NO5: C, 64.21;
H, 4.38; N, 4.68; Found: C, 64.39; H, 4.51; N, 4.77.
trans-(3-Nitrophenyl)(3-(2-nitrophenyl)oxiran-2-yl)methanone (6c)
Grey powder (8.49 g, 0.027 mol, 100% yield): mp 156ꢀ157oC; 1H NMR (400 MHz, DMSOꢀd6)
δ
8.79 (s, 1H, H2ꢀAr2), 8.53 (d, J = 8.2 Hz, 2H, H4,6ꢀAr2), 8.23 (d, J = 8.0 Hz, 1H, H3ꢀAr1),
7.86ꢀ7.11 (m, 2H, H5ꢀAr1, H5ꢀAr2), 7.67ꢀ7.72 (m, 2H, H4,6ꢀAr1), 4.90 (d, J = 1.9 Hz, 1H, H2),
4.65 (d, J = 1.9 Hz, 1H, H3); 13C NMR (125.8 MHz, DMSOꢀd6) δ 191.77 (1C=O), 148.05 (C3ꢀ
Ar2), 147.45 (C2ꢀAr1), 136.05 (C1ꢀAr2), 134.70 (C5ꢀAr1), 134.63 (C6ꢀAr2), 132.15 (C1ꢀAr1),
130.72 (C5ꢀAr2), 129.64 (C4ꢀAr1), 128.17 (C4ꢀAr2), 127.07 (C6ꢀAr1), 124.68 (C3ꢀAr1), 122.71
(C2ꢀAr2), 58.71 (C2), 57.73 (C3). IR (nujol):
ν
1697, 1522 cmꢀ1; HRMS (MALDI) calcd. for
C15H10N2O6 [M+Cs]+ 446.9588, found 446.9581; Anal. Сalcd for C15H10N2O6: C, 57.28; H,
3.32; N, 8.78; Found: C, 57.33; H, 3.21; N, 8.91.
trans-(3-(5-Chloro-2-nitrophenyl)oxiran-2-yl)(4-tolyl)methanone (6d)
Tan powder (8.58 g, 0.027 mol, 100% yield): mp 139 oC; 1H NMR (400 MHz, DMSOꢀd6)
δ 8.24
(d, J = 8.8 Hz, 1H, H3ꢀAr1), 8.01 (d, J = 8.1 Hz, 2H, H2,6ꢀAr2), 7.75 (dd, J = 8.8, 2.4 Hz, 1H,
H4ꢀAr1), 7.59 (d, J = 2.4 Hz, 1H, H6ꢀAr1), 7.37 (d, J = 8.1 Hz, 2H, H3,5ꢀAr2), 4.81 (d, J = 2.1
Hz, 1H, H2), 4.60 (d, J = 2.1 Hz, 1H, H3), 2.41 (s, 3H, Me); 13C NMR (125.8 MHz, DMSOꢀd6) δ
191.86 (1C=O), 146.17 (C2ꢀAr1), 144.85 (C4ꢀAr2), 139.44 (C5ꢀAr1), 134.86 (C1ꢀAr1), 132.64
(C1ꢀAr2), 129.41 (C3ꢀAr2), 129.35 (C4ꢀAr1), 128.56 (C2ꢀAr2), 126.82 (C3ꢀAr1), 126.71 (C6ꢀ
Ar1), 58.24 (C2), 56.65 (C3), 21.20 (Me). IR (nujol):
ν 1681, 1607, 1516; HRMS (MALDI)
calcd. for C16H12ClNO4 [M+Cs]+ 449.9504, found 449.9522; Anal. Сalcd for C16H12ClNO4: C,
60.48; H, 3.81; Cl, 11.16; N, 4.41; Found: C, 60.31; H, 3.71; N, 4.61.

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Synthesis of 2-(2-oxo-2-arylacetamido)benzoic acids (7a-d) was performed according to the
general procedure for the rearrangement with the use of corresponding (3ꢀ(2ꢀnitroaryl)oxiranꢀ2ꢀ
yl)(aryl)methanones (6a-d) instead of 3ꢀ(2ꢀnitroaryl)oxiranꢀ2ꢀcarboxamides (2a-h). Products
7a,b were purified by washing with acetone (3×1 mL), products 7c,d – by recrystallization from
AcOH.
2-[2-Oxo-2-(4-tolyl)acetamido]benzoic acid (7a)
Brown powder (0.35 g, 1.25 mmol, 75% yield): mp 199ꢀ201 oC; 1H NMR (400 MHz, DMSOꢀd6)
δ
12.72 (s, 1H, NH), 8.64 (d, J = 7.5 Hz, 1H, H3ꢀAr1), 8.14 (d, J = 7.8 Hz, 2H, H2,6ꢀAr2), 8.04
(dd, J = 8.1, 1.0 Hz, 1H, H6ꢀAr1), 7.71 (dd, J = 7.6, 7.5 Hz, 1H, H4ꢀAr1), 7.37 (d, J = 7.8 Hz,
2H, H3,5ꢀAr2), 7.28 (dd, J = 7.5, 7.9 Hz, 1H, H5ꢀAr1), 2.42 (s, 3H, Me); 13C NMR (125.8 MHz,
DMSOꢀd6) δ 187.00 (2C=O), 169.15 (CO2H), 160.57 (1C=O), 145.42 (C4ꢀAr2), 139.28 (C2ꢀ
Ar1), 134.19 (C4ꢀAr1), 131.41 (C6ꢀAr1), 130.94 (C2ꢀAr2), 130.38 (C1ꢀAr2), 129.27 (C3ꢀAr2),
124.00 (C5ꢀAr1), 120.13 (C3ꢀAr1), 117.75 (C1ꢀAr1), 21.39 (Me). IR (nujol):
ν 3363, 1678,
1604, 1586, 1521, 1262 cmꢀ1; HRMS (MALDI) calcd. for C16H13NO4 [M+Cs]+ 415.9894, found
415.9887; Anal. Calcd for C16H13NO4: C, 67.84; H, 4.63; N, 4.94. Found: C, 67.92; H, 4.68; N,
4.71.
2-[2-(4-Methoxyphenyl)-2-oxoacetamido]benzoic acid (7b)
Brown powder (0.40 g, 1.35 mmol, 81% yield): mp 178ꢀ181 oC; 1H NMR (400 MHz, DMSOꢀd6)
δ
12.37 (s, 1H, NH), 8.65 (d, J = 8.3 Hz, 1H, H3ꢀAr1), 8.27 (d, J = 8.9 Hz, 2H, H2,6ꢀAr2), 8.05
(d, J = 8.0 Hz, 1H, H6ꢀAr1), 7.67 (dd, J = 7.2, 8.3 Hz, 1H, H4ꢀAr1), 7.26 (dd, J = 7.2, 7.8 Hz,
1H, H5ꢀAr1), 8.10 (d, J = 8.9 Hz, 2H, H3,5ꢀAr2), 3.88 (s, 3H, OMe); 13C NMR (125.8 MHz,
DMSOꢀd6) δ 185.42 (1C=O), 169.12 (CO2H), 164.39 (C4ꢀAr2), 160.81 (2C=O), 139.35 (C2ꢀ
Ar1), 134.14 (C4ꢀAr1), 133.47 (C2ꢀAr2), 131.39 (C6ꢀAr1), 125.61 (C4ꢀAr2), 123.88 (C5ꢀAr1),
120.04 (C3ꢀAr1), 117.60 (C1ꢀAr1), 114.10 (C3ꢀAr2), 55.70 (OMe). IR (nujol):
ν 3472, 3258,
1702, 1674, 1601, 1584, 1528, 1260 cmꢀ1; HRMS (MALDI) calcd. for C16H13NO5 [M+Cs]+
431.9843, found 431.9828; Anal. Calcd for C16H13NO5: C, 64.21; H, 4.38; N, 4.68. Found: C,
64.32; H, 4.37; N, 4.75.
2-[2-(3-Nitrophenyl)-2-oxoacetamido]benzoic acid (7c)
Brown powder (0.45 g, 1.44 mmol, 86% yield): mp 251ꢀ252 oC; 1H NMR (400 MHz, DMSOꢀd6)
δ
12.60 (s, 1H, NH), 9.06 (s, 1H, H2ꢀAr2), 8.70 (d, J = 8.1 Hz, 1H, H3ꢀAr1), 8.58 (d, J = 7.7 Hz,
1H, H6ꢀAr2), 8.54 (dd, J = 8.2, 1.5 Hz, 1H, H4ꢀAr2), 8.09 (dd, J = 7.9, 1.5 Hz, 1H, H6ꢀAr1),
7.89 (dd, J = 7.9, 8.0 Hz, 1H, H5ꢀAr2), 7.72 (ddd, J = 7.9, 7.9, 1.5 Hz, 1H, H4ꢀAr1), 7.30 (dd, J
= 7.9, 7.9 Hz, 1H, H5ꢀAr1); 13C NMR (125.8 MHz, DMSOꢀd6) δ 185.04 (1C=O), 169.14
(CO2H), 159.14 (2C=O), 147.38 (C3ꢀAr2), 139.26 (C2ꢀAr1), 136.71 (C6ꢀAr2), 134.46 (C1ꢀAr2),
134.22 (C4ꢀAr1), 131.44 (C6ꢀAr1), 130.14 (C5ꢀAr2), 128.038 (C4ꢀAr2), 125.58 (C2ꢀAr2),

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123.99 (C5ꢀAr1), 119.88 (C3ꢀAr1), 117.58 (C1ꢀAr1). IR (nujol):
ν
3413, 3189, 1695, 1679,
1588, 1532, 1288 cmꢀ1; HRMS (MALDI) calcd. for C15H10N2O6 [M+2Cs–H]+ 578.8564, found
578.8545; Anal. Сalcd for C15H10N2O6: C, 57.28; H, 3.32; N, 8.78; Found: C, 57.34; H, 3.37; N,
8.89.
5-Chloro-2-[2-oxo-2-(4-tolyl)acetamido]benzoic acid (7d)
o
1
Light yellow powder (0.47 g, 1.49 mmol, 89% yield): mp 257ꢀ258 C; H NMR (400 MHz,
DMSOꢀd6) 12.30 (s, 1H, NH), 8.64 (d, J = 8.9 Hz, 1H, H3ꢀAr1), 8.13 (d, J = 7.9 Hz, 2H, H2,6ꢀ
δ
Ar2), 7.97 (br.s, 1H, H6ꢀAr1), 7.74 (dd, J = 8.8, 1.8 Hz, 1H, H4ꢀAr1), 7.38 (d, J = 7.9, Hz, 2H,
H3,5ꢀAr2), 2.41 (s, 3H, Me); 13C NMR (125.8 MHz, DMSOꢀd6) δ 186.46 (1C=O), 167.80
(CO2H), 160.35 (2C=O), 145.35 (C4ꢀAr2), 138.03 (C2ꢀAr1), 133.70 (C4ꢀAr1), 130.90 (C2ꢀAr2),
130.51 (C6ꢀAr1), 130.25 (C1ꢀAr2), 129.16 (C3ꢀAr2), 127.55 (C5ꢀAr1), 121.83 (C3ꢀAr1), 119.53
(C1ꢀAr1), 21.32 (Me). IR (nujol):
ν
3219, 1703, 1681, 1598, 1577, 1521, 1248 cmꢀ1; HRMS
(MALDI) calcd. for C16H12ClNO4 [M+2Cs–H]+ 581.8480, found 581.8455; Anal. Сalcd for
C16H12ClNO4: C, 60.48; H, 3.81; Cl, 11.16; N, 4.41; Found: C, 60.52; H, 3.73; N, 4.58.
ASSOCIATED CONTENT
Supporting Information
1D and 2D NMR spectra and MALDI massꢀspectra of the products 3a-h and 4a-h;
crystallographic data for 4a,b (CIF), description of quantum chemical computational setup and
comparison of Xꢀray and DFT computed structural parameters of 4a.
AUTHOR INFORMATION
Corresponding Author
eꢀmail: mamedov@iopc.ru
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was partially supported by the Russian scientific foundation (grants No. 14ꢀ23ꢀ00073
and No. 14ꢀ50ꢀ00014).
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DOI: 10.1039/C6RA02586B
Graphical Abstract
A novel acid-catalyzed rearrangement of 2-substituted-3-(2-
nitrophenyl)oxiranes for the synthesis of di- and mono-oxalamides
Vakhid A. Mamedov, Vera L. Mamedova, Gul’nas Z. Khikmatova, Ekaterina V. Mironova, Dmitry B. Krivolapov,
Olga B. Bazanova, Denis V. Chachkov, Sergey A. Katsyuba, Il’dar Kh. Rizvanova and Shamil K. Latypov
OH
3
H
O
O
R1
R1
4
R1
O
1
4
H2SO4 (cat)
AcOH, , 3h
3
EtONa/EtOH
7h, rt
O
O
2
R2
+
ClH2C
R2
5
H
5
NO2
NO2
6NH
2
6
O
12 examples,
61-100% yields
O
1
R2
12 examples,
75-100% yields
A new acidꢀcatalyzed rearrangement of oxiranes for the syntheses of biologically important pharmaceutical
molecules with аnthranilic acid and oxalamide moieties has been discovered.