Transformations of anilides of 3-aryl-2,3-epoxypropionic acids when exposed to acidic agents

Article abstract of DOI:10.1007/s11172-015-1238-2

Anilides of 3-aryl-2,3-epoxypropionic acids on treatment with aqueous HBr gave 3-aryl-3-bromo-2-hydroxypropionic acid anilides and (in some cases) 2-bromo-3-hydroxy regioisomers. Cyclization of these products into 3-arylquinolin-2(1H)-ones was studied.

Full text of DOI:10.1007/s11172-015-1238-2

Russian Chemical Bulletin, International Edition, Vol. 64, No. 12, pp. 2857—2864, December, 2015
2857
Transformations of anilides of 3ꢀarylꢀ2,3ꢀepoxypropionic acids
when exposed to acidic agents*
V. A. Mamedov,a,b V. L. Mamedova,a G. Z. Khikmatova,a A. I. Samigullina,a A. T. Gubaidullin,a
O. B. Bazanova,a I. Kh. Rizvanov,a and O. G. Sinyashina,b
aA. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center of the Russian Academy of Sciences,
8 ul. Acad. Arbuzova, 420088 Kazan, Russian Federation.
Fax: +7 (843) 27 5532. Eꢀmail: mamedov@iopc.ru
bKazan National Research Technological University,
68 ul. Karl Marx, 420015 Kazan, Russian Federation
Anilides of 3ꢀarylꢀ2,3ꢀepoxypropionic acids on treatment with aqueous HBr gave 3ꢀarylꢀ3ꢀ
bromoꢀ2ꢀhydroxypropionic acid anilides and (in some cases) 2ꢀbromoꢀ3ꢀhydroxy regioisomers.
Cyclization of these products into 3ꢀarylquinolinꢀ2(1H)ꢀones was studied.
Key words: anilides of 3ꢀarylꢀ2,3ꢀepoxypropionic acids, anilides of 3ꢀbromoꢀ2ꢀhydroxyꢀ3ꢀ
arylpropionic acids, quinolinꢀ2(1H)ꢀones, Xꢀray diffraction analysis.
Synthetic procedures towards derivatives of 2,3ꢀepꢀ
oxypropionic acid are mostly limited by the Darzens reacꢀ
tion and its modifications.1—8 2,3ꢀEpoxyꢀ3ꢀphenylpropiꢀ
onic acid anilide has been first synthesized in 1919;7 howꢀ
ever, the interest in this compound and other epoxypropiꢀ
onic acid amides has raised due only to the possibility to
obtain enantiopure forms in the presence of chiral cataꢀ
lysts.9—14 Recently,15,16 transformations of 2,3ꢀepoxyproꢀ
pionic acid anilides into quinolinꢀ2ꢀones have been deꢀ
scribed. Synthesis of 4ꢀarylꢀ3ꢀhydroxyquinolinꢀ2(1H)ꢀ
ones from 3ꢀarylꢀ2ꢀcyanepoxypropionic acid Nꢀmethylꢀ
anilides has been published.15 We have synthesized
3ꢀarylquinolinꢀ2(1H)ꢀones starting from Nꢀunsubstituted
anilides of 3ꢀarylꢀ2,3ꢀepoxypropionic acid.16 All these
transformations were performed by treating the starting
compounds with a solution of sulfuric acid in different
solvents. In the present work, we studied a behavior of
a series of 3ꢀarylꢀ2,3ꢀepoxypropionic acid anilides in the
presence of hydrobromic acid and further transformations
of thus obtained hydrobromination products upon treatꢀ
ment with sulfuric acid.
stituents exerting different electronic effects (Scheme 1).
It was found that the synthesis of compounds 1a—e can be
accomplished using equimolar amounts of the reagents,
but a large excess of the corresponding benzaldehyde is
required for the synthesis of compound 1f bearing a strong
electronꢀdonating substituent. We have shown earlier16
that under these conditions transꢀisomers of 3ꢀarylꢀ2,3ꢀ
epoxypropionic acid anilides are mainly formed. Thereꢀ
fore, in the reaction with hydrobromic acid transꢀisomers
of compounds 1a—d,f were used.
Scheme 1
Results and Discussion
R = H (a), Br (b), Me (c), NO2 (d), CF3 (e), OMe (f)
3ꢀArylꢀ2,3ꢀepoxypropionic acid anilides (1a—f) were
synthesized by the reaction of the corresponding benzꢀ
aldehydes with αꢀchloroacetanilide in the presence of
NaOEt in EtOH at room temperature. We used in this
reaction benzaldehydes bearing a wide range of paraꢀsubꢀ
The reaction procedure involves the addition of 47%
aqueous hydrobromic acid to the solutions of compounds
1a—e in acetone and subsequent maintaining the reacꢀ
tion mixture at room temperature for 1 h. The reaction
products either precipitate from the reaction mixture or
were precipitated by adding water. The yields were nearly
* Dedicated to Academician of the Russian Academy of Sciences
N. S. Zefirov on the occasion of his 80th birthday.
1
quantitative. The changes in the H NMR spectra indiꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2857—2864, December, 2015.
1066ꢀ5285/15/6412ꢀ2857 © 2015 Springer Science+Business Media, Inc.

2858
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015
Mamedov et al.
cate that the epoxide ring opening produces hydrobromiꢀ
nation products.
O(1)
N(1)
С(1)
С(2)
The acidꢀcatalyzed ring opening of epoxides may follow
different directions; therefore, hydrobromination of 3ꢀarylꢀ
2,3ꢀepoxypropionic acid anilides 1 can afford different
isomeric products, namely, anilides of 3ꢀbromoꢀ2ꢀhyꢀ
droxyꢀ (2) or 2ꢀbromoꢀ3ꢀhydroxyꢀ3ꢀarylpropionic acids
(3) (Scheme 2). In turn, each regioisomer can exist in two
diastereomeric forms (syn and anti) consisting of one
pair of enantiomers. It is impossible to make a conclusion
about preferable direction of the epoxide ring opening due
to the scarce published data. A detailed study has been
undertaken only for hydrochlorination of methyl 2,3ꢀepꢀ
oxyꢀ3ꢀpnehylpropionate with hydrogen chloride in
benzene to give methyl 3ꢀchloroꢀ2ꢀhydroxyꢀ3ꢀphenylꢀ
propionate.17
C(10)
O(2)
С(3)
С(30)
Br(3)
Fig. 1. Molecular structure of compound antiꢀ2a. Nonhydrogen
atoms are depicted at the 30% probability level; hydrogen atoms
are shown as spheres of arbitrary radius.
1H NMR chemical shifts of the C(2)H and C(3)H
protons of transꢀisomers of 3ꢀarylꢀ2,3ꢀepoxytropionic acid
anilides (1a—f) and hydrobromination products are sumꢀ
marized in Table 1. From a comparison of these data with
the data available for methyl 3ꢀchloroꢀ2ꢀhydroxyꢀ3ꢀ
phenylpropionate,17,18 the structures of anilides of 3ꢀbroꢀ
moꢀ2ꢀhydroxyꢀ3ꢀaryl propionic acid were supposedly
ascribed to products 2a—c (see Scheme 2, route a).
Taking into account the same published data,17,18 a diaꢀ
Scheme 2
3
stereomers with the lower JH,H value were identiꢀ
fied as anti. The syn : anti diastereomer ratios calculated
from the integral intensities of the signals of the crude
products are given in Table 1. We succeeded in resolving
the individual syn and anti diastereomers of compounds
2a and 2b.
Single crystal Xꢀray diffraction structure of antiꢀ2a
(a single crystal was grown from a solution in chloroform)
is shown on Fig. 1. According to Xꢀray diffraction analysis
data, compound 2a crystallizes as one independent moleꢀ
cule in the asymmetric part of the rhombic unit cell. The
dihedral angle between the planes of two phenyl moieties
is 36.6(2)°.
Table 1. 1H NMR spectroscopy data (600 MHz, DMSOꢀd6) of epoxides 1 and hydrobromination products
Comꢀ
pound
δ (J/Hz)
Product
R
syn/anti
1
Product
syn
anti
1а
1b
1c
1d
1e
1f
3.78 (d, 1 Н, J = 1.9);
4.20 (d, 1 Н, J = 1.9)
3.76 (br.s, 1 Н);
4.66 (d, 1 Н, J = 7.6);
5.36 (d, 1 Н, J = 7.6)
4.62 (d, 1 Н, J = 7.2);
5.35 (d, 1 Н, J = 7.2)
4.65 (d, 1 Н, J = 7.5);
5.35 (d, 1 Н, J = 7.5)
4.58 (d, 1 Н, J = 9.7);
5.12 (d, 1 Н, J = 9.7)
4.58 (d, 1 Н, J = 9.8);
5.06 (d, 1 Н, J = 9.8)
4.42 (d, 1 Н, J = 3.9);
5.57 (d, 1 Н, J = 3.9)
4.38 (d, 1 Н, J = 4.0);
5.53 (d, 1 Н, J = 4.0)
4.40 (d, 1 Н, J = 4.1);
5.54 (d, 1 Н, J = 4.1)
4.70 (d, 1 Н, J = 7.1);
5.52 (d, 1 Н, J = 7.1)
4.68 (d, 1 Н, J = 7.3);
5.45 (d, 1 Н, J = 7.3)
2a
2b
2c
3d
3e
6
H
1 : 0.7
1 : 0.5
Br
4.21 (br.s, 1 Н)
3.76 (d, 1 Н, J = 1.7);
4.15 (d, 1 Н, J = 1.7)
3.84 (d, 1 Н, J = 1.7);
4.42 (d, 1 Н, J = 1.7)
3.80 (d, 1 Н, J = 1.29);
4.34 (d, 1 Н, J = 1.28)
3.80 (d, 1 Н, J = 1.7);
4.13 (d, 1 Н, J = 1.7)
Me
0.8 : 1
NO2
CF3
OMe
0.05 : 1
0.05 : 1
1 : 0.3c
4.17 (s, 2 Н, Н(3))a
6.47 (s, 1 Н, Н(3))b
a Keto form. b Enol form. b A keto : enol ratio.

Anilides of 3ꢀarylꢀ2,3ꢀepoxipropionic acids
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015 2859
b
a
O(1)
O(2)
H(2)
O(1)
H(1)
O(2)
N(1)
H(11)
O(1)
N(1)
O(1)
H(2)
H(11)
Fig. 2. a, HꢀDimers in the crystal of compound formed by the NH...O hydrogen bonds (dashed lines). b, Fragment of crystal packing
of molecules 2a; view along the 0b axis.
Analysis of intermolecular interactions in the crystal
indicates that the main supramolecular synthon is a symꢀ
metric Hꢀdimer formed by a pair of the classical N—H...O
hydrogen bonds (Fig. 2, a). The participation of the O(1)
carbonyl oxygen in the bifurcated hydrogen bonds results
in arrangement of the Hꢀdimers in zigzag chains parallel
to the 0ab plane (Fig. 2, b). In general, the crystal strucꢀ
ture of 2a shows antiparallel packing of such zigzag motifs
along the 0c axes; the calculated molecular packing index
is 66.3%. Note that only van der Waals forces virtually
assemble the layers, since the parameters of π—π electron
interactions between the aromatic moieties of the adjaꢀ
cent layers are close to the boundary values of the default
criteria used in PLATON software for identification of
such contacts.
Parameters of intermolecular and intramolecular conꢀ
tacts in compound 2a found by Xꢀray diffraction analysis
are summarized in Table 2.
Compounds 2a—c as either the diastereomeric mixꢀ
tures or individual stereoisomers were involved in intraꢀ
molecular cyclization16 on treatment with sulfuric acid
in dimethyl sulfate at 100 °C (Scheme 3). The reaction is
accompanied by the aryl group migration to give 3ꢀarylꢀ
quinolinꢀ2(1H)ꢀones 4a—c. Compounds 4a,b,d have
been synthesized by us earlier from the corresponding
2,3ꢀepoxyꢀ3ꢀarylpropionic acid anilides.16 Compound 4c
was first synthesized in the present work starting from
both 3ꢀbromoꢀ2ꢀhydroxyꢀ3ꢀ(4ꢀmethylphenyl)propꢀ
ionic acid anilide (2c) and 2,3ꢀepoxyꢀ3ꢀ(4ꢀmethylphenꢀ
yl)propionic acid anilide (1c). Trifluoromethyl derivaꢀ
Table 2. Parameters of intramolecular and intermolecular interaction in the crystals
D—H⋅⋅⋅A
D—H
H⋅⋅⋅A
D⋅⋅⋅A
DHA angle
/deg
Symmetry code
Å
Compound 2а
N(1)—H(1)...O(2)
C(35)—H(35)...Br(3)
N(1)—H(1)...O(2)
O(2)—H(2)...O(1)
C(11)—H(11)...O(1)
0.86
0.93
0.86
0.82
0.93
2.26
2.91
2.42
1.94
2.43
2.668(4)
3.237(5)
3.162(4)
2.707(3)
3.278(5)
109
102
145
156
152
—
—
1 – x, 1 – y, –z
3/2 – x, 1/2 + y, z
–1/2 + x, 1/2 – y, –z
Compound 5
N(1)—H(1)...Br(2)
C(3)—H(3)...O(1)
C(11)—H(11)...O(1)
C(14)—H(14)...O(41A)
C(35)—H(35)...Br(2)
C(12)—H(12)...O(1)
0.88(5)
0.93
0.93
0.93
0.93
2.46(4)
2.32
2.24
2.60
2.57
3.016(6)
2.737(8)
2.836(9)
2.946(12)
3.278(8)
3.309(9)
122(4)
107
121
103
133
ВМВ
ВМВ
ВМВ
ВМВ
ВМВ
0.93
2.44
155
2 – x, 1 – y, –z

2860
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015
Mamedov et al.
tive was synthesized only from epoxy anilide 1e (see
Scheme 3).
The data presented in Table 1 are not sufficient for the
ascribing the structure of hydrobrominated compounds
3d,e either to anilides of 3ꢀarylꢀ2ꢀbromoꢀ3ꢀhydroxyꢀ
propionic acid (see Scheme 2, route b) containing preꢀ
dominantly the anti diastereomer or to a mixture of
synꢀdiastereomers distinguished by positions of the Br
atom and the OH group (see Scheme 2, routes a and b)
with predominant isomer resulting from the route a. If the
second possibility is implemented, the intramolecular
cyclization catalyzed by sulfuric acid in dimethyl sulfate
should result in 3ꢀarylquinolinꢀ2(1H)ꢀones similarly to
compounds 2a—c. According to the published data,16
2,3ꢀepoxyꢀ3ꢀ(4ꢀnitrophenyl)propionic acid anilide (1d)
produces 3ꢀ(4ꢀnitrophenyl)quinolinꢀ2(1H)ꢀone (4d) in
quantitative yield; in the present work, compound 1e was
transformed into 3ꢀ(4ꢀtrifluoromethylphenyl)quuinolinꢀ2ꢀ
one with high yield. However, the reactions of compounds 3d
and 3e bearing the paraꢀpositioned strong electronꢀwithꢀ
drawing substituents NO2 and CF3 afford hardly separable
Scheme 3
R = H (a), Br (b), Me (c), NO2 (d), CF3 (e)
i. H2SO4, Me2SO4, 100 °C.
A plausible mechanism for the formation of 3ꢀarylquinꢀ
olinꢀ2(1H)ꢀones (4a—c) from 3ꢀarylꢀ3ꢀbromoꢀ2ꢀhydroxyꢀ
propionic acid anilides 2a,c is shown on Scheme 4. Migration
of the aryl group can be explained by its anchimeric assisꢀ
tance19 in stabilization of carbocation resulting from the
hydroxy group cleavage. This leads to the intermediate
structure A, which undergoes intramolecular Friedel—Crafts
alkylation to give intermediate B. Stabilization of structure
B occurs via the loss of HBr to produce the target product 4.
1
mixtures of the products. In H NMR spectra of these
mixtures, no signals characteristic of 3ꢀarylquinolinꢀ
2(1H)ꢀones were found. These facts lead to the conclusion
that the hydrobromination of compounds 1d,e follows the
route b to yield regioisomers 3d,e.
According to Xꢀray diffraction study of a single crystal
grown from a chloroform solution of the reaction mixture
obtained by the reaction of 3d with sulfuric acid in dimeꢀ
thyl sulfate, the product has structure of 2ꢀbromoꢀ3ꢀ(4ꢀ
nitrophenyl)acrylic acid Nꢀ(4ꢀmethoxysulfonylphenyl)ꢀ
amide (5) (Fig. 3).
Scheme 4
In contrast to compound 2a, the molecule of 5 has
a planar geometry with strong conjugation, which is favored
by the presence of two substituents on the aromatic ring
participating in conjugation. At the same time, the methꢀ
oxysulfonyl group is disordered over two positions with
O(43A)
S(40)
O(1)
C(3)
C(2)
C(10)
C(1)
N(1)
H(1)
C(30)
O(37)
N(35)
Br(2)
O(36)
Fig. 3. Molecular structure of compound 5. Nonhydrogen atoms
are depicted at the 30% probability level; hydrogen atoms are
shown as spheres of arbitrary radius. The methoxysulfonyl group
is shown in the position with population parameter of 0.68.

Anilides of 3ꢀarylꢀ2,3ꢀepoxipropionic acids
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015 2861
Table 3. Parameters of πꢀinteractions in the crystals of comꢀ
pound 5
a
b
πꢀContact
da/Å
ϕ /deg
Symmetry code
Cg(1)...Cg(2)c*
Cg(2)...Cg(1)*
Cg(1)...Cg(2)**
Cg(2)...Cg(1)**
3.812(4)
3.811(4)
4.948(5)
4.948(5)
4.8
4.8
4.8
4.8
1 – x, 1 – y, –z
1 – x, 1 – y, –z
1 – x, 2 – y, –z
1 – x, 2 – y, –z
a
a A distance between the centers of the cycles, Cg—Cg.
b Dihedral angle between the cycle planes.
c
Cg1ꢀcycle: C(10)—C(11)—C(12)—C(13)—C(14)—C(15),
0
Cg2ꢀcycle: C(30)—C(31)—C(32)—C(33)—C(34)—C(35). Symꢀ
metry codes for the interacting molecules: (1 – x, 1 – y, –z)(*)
and (1 – x, 2 – y, –z)(**).
b
c
population parameters of 0.68 and 0.32. The planes of two
aromatic substituents form a dihedral angle equal to
4.8(3)°. Despite the presence of amide function, it is not
involved in intramolecular hydrogen bonding due apparꢀ
ently to the steric restrictions. In general, the intramolecꢀ
ular contacts are realized via the C—H...O hydrogen bonds
and πꢀelectron contacts (see Tables 2 and 3). These inꢀ
tramolecular interactions form a layered supramolecular
structure parallel to the 0ab plane; the crystal packing is
formed along the 0c axis (Fig. 4).
b
Apparently, product 5 is resulted from two reactions:
acidꢀcatalyzed dehydration to give the corresponding
acrylic anilide and introduction of the methoxysulfonyl
group into the phenyl ring (Scheme 5).
Fig. 4. a, A fragment of the layered supramolecular structure in
crystal, the CH...O hydrogen bonds and πꢀcontacts are shown by
dashed lines. b, Mutual packing of the layers in crystal 5. One of
the layers is shown as ballꢀandꢀsticks models.
Scheme 5
Scheme 6
Reagents and conditions: H+, Me2SO4, 100 °C.
Under hydrobromination conditions, 2,3ꢀepoxyꢀ3ꢀ(4ꢀ
methoxyphenyl)propionic acid anilide (1f) undergoes reꢀ
arrangement accompanied by Hꢀmigration from C(2) to
C(3) to give 3ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxopropionic acid
anilide (6) existing in the solutions in tautomeric equilibꢀ
rium with the enol form (Scheme 6). A tautomeric ratio
the attempt to synthesize 3ꢀ(4ꢀmethoxyphenyl)quinolinꢀ
2ꢀone from 2,3ꢀepoxyꢀ3ꢀ(4ꢀmethoxyphenyl)propionic
acid anilide (1f) by treatment with sulfuric acid in dimethyl
sulfate gives the same results.
1
found by H NMR spectroscopy and the chemical shifts
of the C(3)H protons are given in Table 1. It is of note that

2862
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015
Mamedov et al.
1H NMR spectra of crude products are given. Other parameters
and yields are given for trans isomers. trans : cis = 1 : 0.27. Yield
68%, m.p. 149—151 °C. Found (%): C, 75.82; H, 5.99; N, 5.58.
C16H15NO2. Calculated (%): C, 75.87; H, 5.97; N, 5.53. IR,
ν/cm–1: 744, 890, 1550, 1602, 1677, 3275. 1H NMR, δ: 3.76,
4.15 (both d, 1 H each, H(2), H(3), J = 1.7 Hz); 7.09 (dd, 1 H,
HPh(4), J1 = J2 = 7.4 Hz); 7.22 (d, 2 H, HAr(3) and HAr(5),
J = 7.8 Hz); 7.29 (d, 2 H, HPh(2) and HPh(6), J = 8.0 Hz); 7.34
(dd, 2 H, HPh(3) and HPh(5), J1 = 7.9 Hz, J2 = 7.5 Hz); 7.67
(d, 2 H, HAr(2) and HAr(6), J = 7.8 Hz); 10.23 (s, 1 H, NH). MS,
m/z: 276.1016 [M + Na]+. Calculated: [M + Na]+ 276.0995.
2,3ꢀEpoxyꢀ3ꢀ(4ꢀtrifluoromethylphenyl)propionic acid anilide
(1e), trans : cis = 1 : 0. Yield 99%, m.p. 187 °C. Found (%):
C, 62.58; H, 3.90; F, 18,59; N, 4.52. C16H12F3NO2. Calculatꢀ
ed (%): C, 62.54; H, 3.94, F, 18.55, N, 4.56. IR, ν/cm–1: 1116,
1549, 1605, 1680, 3348. 1H NMR, δ: 3.80, 4.34 (both d, 1 H
each, H(2), H(3), J = 1.3 Hz); 7.10 (dd, 1 H, HPh(4), J1 = J2 =
= 7.4 Hz); 7.34 (dd, 2 H, HPh(3) and HPh(5), J1 = 7.6 Hz,
J2 = 8.1 Hz); 7.63 (d, 2 H, HAr(2) and HAr(6), J = 8.6 Hz); 7.65
(d, 2 H, HAr(3) and HAr(5), J = 8.7 Hz); 7.77 (d, 2 H, HPh(2) and
HPh(6), J = 8.1 Hz); 10.32 (d, 1 H, NH). MS, m/z: 330.0718
[M + Na]+. Calculated: [M + Na]+ 330.0712.
In summary, the directions of the epoxide ring opening
in the reactions of 3ꢀarylꢀ2,3ꢀepoxypropionic acid anilides
with hydrobromic acid depend on electronic effects of the
substituents on the aryl fragment. Treatment of 3ꢀarylꢀ3ꢀ
bromoꢀ2ꢀhydroxypropionic acid anilides with sulfuric acid
in dimethyl sulfate at 100 °C produces 3ꢀarylquinolinꢀ
2(1H)ꢀones, which being the analogs of natural alkaloids are
of interest from the viewpoint of their biological activity.
Experimental
Melting points were measured on a Stuart SMPꢀ10 apparaꢀ
tus. IR spectra were recorded with a Bruker Vectorꢀ22 instruꢀ
ment in Nujol. 1H NMR spectra were run on a Bruker Avanceꢀ
600 instrument in DMSOꢀd6, the chemical shifts are given in the
δ scale. High resolution MALDI mass spectrometry was perꢀ
formed with an UltraFlex III TOF/TOF spectrometer operating
in a reflectron mode. 2,5ꢀDihydroxybenzoic acid and 4ꢀnitroꢀ
aniline were used as the matrixes. PEGꢀ400 was used as an interꢀ
nal standard of mass calibration.
Single crystal Xꢀray diffraction analysis of compounds 2a and 5
was carried out in the Laboratory of Diffraction Research
Methods, the Federal MultipleꢀAccess Center, A. E. Arbuzov
Institute of Organic and Physical Chemistry of Kazan Research
Center of the RAS. The diffraction experiments were performed
with an automatized Bruker Smart Apex II CCD single crystal
Xꢀray diffractometer (MoꢀKα radiation, graphite monochromaꢀ
tor, λ = 0.71073 Å, ω scan mode) at 23 °C. The data collection,
data editing, and refinement of the unit cell parameters were
performed with APEX2 program package.20 A semiꢀempirical
absorption corrections were applied using SADABS program.21
The structures were solved by direct methods and refined by full
matrix leastꢀsquares first isotropically, then anisotropically (for
all nonꢀhydrogen atoms) employing SHELXL software.22 The
hydrogen atoms of the hydroxy and amide groups of compounds 2a
and 5 were identified from difference electron density map and
refined in isotropic approximation; all other hydrogen atoms
were positioned using stoichiometric criteria and refined using
a riding model. All computations were performed with WinGX
program.23 PLATON24 and Mercury25 programs were used for
the analysis and visualization of the intramolecular interactions.
Crystallographic parameters of compounds 2a and 5, details of
the Xꢀray experiments, structure solution, and refinement
parameters are summarized in Table 2. Crystallographic data
for compounds 2a and 5 were deposited with the Cambridge
Crystallographic Data Centre (CCDC 1063781 and 1063782).
These data can be obtained free of charge via Internet at
www.ccdc.cam.ac.uk/data_request/cif.
2,3ꢀEpoxyꢀ3ꢀ(4ꢀmethoxyphenyl)propionic acid anilide (1f),
trans : cis = 1 : 0. Yield 81%, m.p. 168—169 °C. Found (%):
C, 71.39; H, 5.30; N, 5.25. C16H15NO3. Calculated (%): C, 71.36;
H, 5.61; N, 5.20. IR, ν/cm–1: 1248, 1544, 1601, 1678, 3299.
1H NMR, δ: 3.77 (s, 3 H, MeO); 3.80, 4.13 (both d, 1 H each,
H(2), H(3), J = 1.7 Hz); 6.97 (d, 2 H, HAr(3) and HAr(5), J= 8.7 Hz);
7.09 (dd, 1 H, HPh(4), J1 = J2 = 7.3 Hz); 7.33 (d, 2 H, HAr(2)
and HAr(6), J = 8.7 Hz); 7.33 (dd, 2 H, HPh(3) and HPh(5),
J1 = 7.3 Hz, J2 = 7.5 Hz); 7.67 (d, 2 H, HPh(2) and HPh(6),
J = 7.6 Hz); 10.29 (c, 1 H, NH). MS, m/z: 402.0077 [M + Cs]+.
Calculated: [M + Cs]+ 402.0101.
Reactions of compound 1a—f with HBr. To a solution of the
corresponding 3ꢀarylꢀ2,3ꢀepoxypropionic acid anilide (1 mL) in
acetone (10 mL), 47% aqueous hydrobromic acid (10 mL) was
added. The reaction mixture was kept at room temperature for
1 h. After this period of time, products either precipitate from the
reaction mixture or water was added to precipitate the target
product. The precipitates were collected by filtration. According
to 1H NMR spectroscopy, the products were pure and contain
no impurities. The diastereomeric ratios of products 2a—c, 3d,e
and tautomeric ratio of 6 are given in Table 1. The yields were
nearly quantitative.
antiꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀphenylpropionic acid anilide
(antiꢀ2a). The product precipitated from the reaction mixture
within 20 min from the reaction onset, yield 0.08 g (25%), m.p.
143—145 °C. Found (%): C, 56.31; H, 4.48; Br, 25.02, N, 4.35.
C15H14BrNO2. Calculated (%): C, 56.27; H, 4.41; Br, 24.96;
N, 4.37. IR, ν/cm–1: 659, 1112, 1540, 1597, 1665, 3307. 1H NMR,
δ: 4.42, 5.57 (both d, 1 H each, H(2), H(3), J = 3.9 Hz); 7.07,
7.30, 7.36 (all dd, 1 H, 3 H, 2 H, HPh(3), HPh(4), HPh(5), J = 7.2 Hz,
J = 7.8 Hz, J = 7.2 Hz); 7.59, 7.65 (both d, 2 H each, HPh(1),
HPh(6), J = 7.2 Hz, J = 7.8 Hz). MS, m/z: 451.9257 [M + Cs]+.
Calculated: [M + Cs]+ 451.9281.
synꢀ3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀphenylpropionic acid anilide (synꢀ2a).
After filtration of antiꢀdiastereomer, the filtrate was kept at room
temperature for another 40 min, the precipitate containing
a 1 : 1 mixture of antiꢀ and synꢀdiastereomers was collected by
filtration, yield 0.10 g (30%). The filtrate was diluted with water
(30 mL), the precipitate of synꢀ2a was collected, yield 0.11 g
(35%), m.p. 130—132 °C. Found (%): C, 56.29; H, 4.43; Br, 25.04,
3ꢀArylꢀ2,3ꢀepoxypropionic acid anilides were synthesized by
mixing chloroacetanilide and the corresponding benzaldehyde
in equimolar amounts for compounds 1a,b,d,e or using a 5ꢀfold
excess of benzaldehyde for compounds 1c,f. The reactions were
carried out in EtOH. Then ethanol solution of NaOEt in an
amount equimolar to chloroacetic acid anilide was added folꢀ
lowed by stirring the reaction mixture for 5 h. Similar procedure
and physicochemical parameters of compounds 1a,b,d have been
published earlier.16 Physicochemical properties of compounds
1c,e,f are given below.
2,3ꢀEpoxyꢀ3ꢀ(4ꢀmethylphenyl)propionic acid anilide (1c).
Here and hereafter the trans : cis isomeric ratios determined from

Anilides of 3ꢀarylꢀ2,3ꢀepoxipropionic acids
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015 2863
N, 4.39. C15H14BrNO2. Calculated (%): C, 56.27; H, 4.41;
Br, 24.96; N, 4.37. IR, ν/cm–1: 697, 767, 1101, 1543, 1602. 1671,
3354, 3474. 1H NMR, δ: 4.66, 5.36 (both d, 1 H each, H(2),
H(3), J = 7.6 Hz); 7.07, 7.30, 7.35 (all dd, 1 H, 3 H, 2 H, HPh(3),
HPh(4), HPh(5), J = 7.3 Hz, J = 7.8 Hz, J = 7.3 Hz); 7.50, 7.59
(both d, 2 H each, HPh(2), HPh(6), J = 7.1 Hz, J = 7.7 Hz);
10.04 (s, 1 H, NH). MS, m/z: 359.9841 [M + K]+. Calculated:
[M + K]+ 359.9820.
synꢀ3ꢀBromoꢀ3ꢀ(4ꢀbromophenyl)ꢀ2ꢀhydroxypropionic acid
anilide (synꢀ2b) precipitated from the reaction mixture within
20 min from the reaction onset. Yield 0.18 g (45%), m.p.
147—148 °C. Found (%): C, 45.09; H, 3.33; Br, 40.07; N, 3.49.
C15H13Br2NO2. Calculated (%): C, 45.14; H, 3.28; Br, 40.04;
N, 3.51. IR, ν/cm–1: 751, 1107, 1531, 1597, 1635, 3285. 1H NMR,
δ: 4.62, 5.35 (both d, 1 H each, H(2), H(3), J = 7.2 Hz); 7.07
(dd, 1 H, HPh(4), J1 = J2 = 7.5 Hz); 7.30 (dd, 2 H, HPh(3) and
HPh(5), J1 = 7.7 Hz, J2 = 7.9 Hz); 7.45 (d, 2 H, HAr(2) and
HAr(6), J = 8.5 Hz); 7.53 (d, 2 H, HAr(3) and HAr(5), J = 8.5 Hz);
7.56 (d, 2 H, HPh(2) and HPh(6), J = 7.9 Hz); 10.02 (s, 1 H, NH).
13C NMR, δ: 56.6 (CHBr), 75.5 (CHOH), 120.4 (oꢀCHNHPh),
122.0 (=CBr),124.3 (pꢀCHNHPh), 129.1 (=CH), 131.3 (=CH),
131.6 (=CH), 138.6 (=C), 139.3 (=C), 169.8 (C=O). MS, m/z:
531.8357 [M + Cs]+. Calculated: [M + Cs]+ 531.8342.
antiꢀ3ꢀBromoꢀ3ꢀ(4ꢀbromophenyl)ꢀ2ꢀhydroxypropionic acid
anilide (antiꢀ2b). After synꢀdiastereomer was collected, the reacꢀ
tion mixture was kept at room temperature for another 40 min to
give a mixture of antiꢀ and synꢀdiastereomers in a ratio of 0.5 : 1,
yield 0.12 g (30%). This mixture was washed with CHCl3
(3 mL). Removal of the volatiles from the filtrate afforded antiꢀ2b
in the yield of 0.07 g (18%), m.p. 168—170 °C. Found (%):
C, 45.43; H, 3.41; Br, 40.96; N, 3.37. C15H13Br2NO2. Calculatꢀ
ed (%): C, 45.14; H, 3.28; Br, 40.04; N, 3.51. IR, ν/cm–1: 1112,
1544, 1603, 1659, 3339. 1H NMR, δ: 4.38, 5.53 (both d, 1 H each,
H(2), H(3), J = 4.0 Hz); 7.08 (dd, 1 H, HPh(4), J1 = J2 = 7.4 Hz);
7.29 (dd, 2 H, HPh(3) and HPh(5), J1 = J2 = 7.5 Hz); 7.51 (d, 4 H,
HAr(2), HAr(3), HAr(5), and HAr(6), J = 3.8 Hz); 7.53 (dd, 2 H,
HPh(2) and HPh(6), J1 = J2 = 7.5 Hz); 9.75 (s, 1 H, NH). 13C NMR,
δ: 56.6 (CHBr), 75.5 (CHOH), 120.4 (oꢀCHNHPh), 122.0 (=CBr),
124.3 (pꢀCHNHPh), 129.1 (=CH), 131.3 (=CH), 131.6 (=CH),
138.6 (=C), 139.3 (=C), 169.8 (C=O). MS, m/z: 531.8367
[M + Cs]+. Calculated: [M + Cs]+ 531.8342.
(s, 1 H, NH). MS, m/z: 465.9433 [M + Cs]+. Calculated: [M + Cs]+
465.9413.
antiꢀ2ꢀBromoꢀ3ꢀhydroxyꢀ3ꢀ(4ꢀnitrophenyl)propionic acid
anilide (3d) precipitated from the reaction mixture within 40 min
after the reaction onset, yield 0.30 g (83%), m.p. 161 °C. Found (%):
C, 49.38; H, 3.31; Br, 21.53; N, 7.38. C15H13BrN2O4. Calculatꢀ
ed (%): C, 49.33; H, 3.59; Br, 21.88; N, 7.67. IR, ν/cm–1: 875,
1115, 1350, 1517, 1599, 1663, 3321. 1H NMR, δ: 4.70, 5.52
(both d, 1 H each, H(2), H(3), J = 7.1 Hz); 7.08 (dd, 1 H, H(4),
Ph, J1 = J2 = 7.3 Hz); 7.31 (dd, 2 H, HPh(3) and HPh(5), J1 = 7.5 Hz,
J2 = 7.9 Hz); 7.60 (d, 2 H, HPh(2) and HPh(6), J = 7.8 Hz); 7.79
(d, 2 H, HAr(2) and HAr(6), J = 8.6 Hz); 8.22 (d, 2 H, HAr(3) and
HAr(5)); 10.07 (s, 1 H, NH). 13C NMR, δ: 52.3 (CHBr), 75.8
(CHOH), 120.2 (oꢀCHNHPh), 123.8 (=CH), 124.3 (pꢀCHNHPh),
129.2 (=CH), 130.8 (=CH), 138.8 (=C), 146.3 (=C), 147.7 (=C),
169.3 (C=O). The filtrate was diluted with water (30 mL), filtraꢀ
tion afforded a mixture of antiꢀ and synꢀdiastereomers in a ratio
of 2 : 1, yield 0.05 g (14%). MS, m/z: 365.0118 [M + H]+. Calcuꢀ
lated: [M + H]+ 365.0131.
antiꢀ2ꢀBromoꢀ3ꢀhydroxyꢀ3ꢀ(3ꢀtrifluoromethylphenyl)propioꢀ
nic acid anilide (antiꢀ3e) precipitated from the reaction mixture
within 40 min from the reaction onset, yield 0.32 g (86%), m.p.
168 °C. Found (%): C, 49.40; H, 3.24; Br, 20.93; F, 14,57; N, 3.32.
C16H13BrF3NO2. Calculated (%): C, 49.51; H, 3.38; Br, 20,58;
F, 14.68; N, 3.61. IR, ν/cm–1: 749, 1113, 1127, 1329, 1530,
1599, 1636, 3293. 1H NMR, δ: 4.68, 5.45 (both d, 1 H each,
H(2), H(3), both J = 7.3 Hz); 7.08 (dd, 1 H, HPh(4), J1 = J2 =
= 7.4 Hz); 7.31 (dd, 2 H, HPh(3) and HPh(5), J1 = 7.6 Hz,
J2 = 7.7 Hz); 7.59 (d, 2 H, HPh(2) and HPh(6), J = 7.7 Hz); 7.73
(br.s, 4 H, HAr(2), HAr(3), HAr(5) and HAr(6)); 10.07 (s, 1 H,
NH). The filtrate was diluted with water (30 mL), the precipitate
containing a mixture of antiꢀ and synꢀdiastereomers in a ratio of
2 : 1 was collected by filtration, yield 0.05 g (13%). MS, m/z:
519.9149 [M + Cs]+. Calculated: [M + Cs]+ 519.9131.
3ꢀArylquinolinꢀ2(1H)ꢀones (4a—c) were synthesized by heatꢀ
ing the corresponding 3ꢀarylꢀ3ꢀbromoꢀ2ꢀhydroxypropionic acid
anilide (2a—c) (1 mmol) in a mixture of dimethyl sulfate (4 mL)
and concentrated H2SO4 (1 mL) at 100 °C for 5 h. The reaction
mixture was poured into water, the precipitate formed was colꢀ
lected by filtration. Compounds 4a,b were synthesized earlier21
from the corresponding 3ꢀarylꢀ2,3ꢀepoxypropionic acid anilides
(1a,b); therefore, herein only the yields of 4a,b are given. Comꢀ
pound 4c was first synthesized and fully characterized in the
present work.
3ꢀPhenylquinolinꢀ2(1H)ꢀone (4a) was synthesized from synꢀ2a,
antiꢀ2a, and a mixture of diastereomers synꢀ2a and antiꢀ2a (1 : 1)
in the yields of 78, 82, and 80%, respectively.
3ꢀ(4ꢀBromophenyl)quinolinꢀ2(1H)ꢀone (4b) was synthesized
from synꢀ2b in 89% yield.
3ꢀ(4ꢀMethylphenyl)quinolinꢀ2(1H)ꢀone (4c) was synthesized
following the known procedure16 from a mixture of synꢀ2c and
antiꢀ2c (0.8 : 1) in 83% yield and from compound 1c in 70%
yield, m.p. 209—211 °C. Found (%): C, 81.72; H, 5.73; N, 6.02.
C16H13NO. Calculated (%): C, 81.67; H, 5.58, N, 5.95. IR,
ν/cm–1: 1658. 1H NMR, δ: 2.34 (s, 3 H, Me); 7.18, 7.48 (both dd,
1 H each, H(6), H(7) in the quinoline fragment (Q), J1 = 7.4 Hz,
J2 = 7.6 Hz, J3 = 7.4 Hz, J4 = 8.1 Hz); 7.23 (d, 2 H, HAr(3) and
HAr(5), J = 8.1 Hz); 7.34, 7.71 (both d, 1 H each, HQ(5), HQ(8),
J = 8.1 Hz, J = 7.6 Hz); 7.66 (d, 2 H, HAr(2) and HAr(6), J = 8.0 Hz);
8.04 (s, 1 H, =CH); 11.88 (br.s, 1 H, NH). MS, m/z: 368.0075
[M + Cs]+. Calculated: [M + Cs]+ 368.0046.
3ꢀBromoꢀ2ꢀhydroxyꢀ3ꢀ(4ꢀmethylphenyl)propionic acid anilꢀ
ide (2c). The precipitate formed in the reaction mixture within
20 min after the reaction onset contained synꢀ and antiꢀdiastereoꢀ
mers in a ratio of 0.8 : 1, yield 0.19 g (58%). Found (%): C, 57.59;
H, 4.87; Br, 23.99; N, 4.02. C16H16BrNO2. Calculated (%):
C, 57.50; H, 4.83; Br, 23.91; N, 4.19. IR, ν/cm–1: 753, 1053, 1549,
1
1601, 1656. H NMR, δ: 2.28 (s, 3 H, Me); 4.40, 5.54 (both d,
1 H each, Hanti(2), Hanti(3), J = 4.1 Hz); 4.65, 5.35 (both d,
1 H each, Hsyn(2), Hsyn(3), J = 7.5 Hz); 6.90—7.70 (m, 9 H,
C6H4, C6H5); 9.80 (s, 1 H, NHanti); 10.03 (s, 1 H, NHsyn). The
filtrate was kept at room temperature for another 40 min, the
filtrate was collected by filtration, washed with chloroform to
give 0.11 g (33%) of the substance, which was supposedly attribꢀ
uted to antiꢀ2ꢀbromoꢀ3ꢀhydroxyꢀ3ꢀ(4ꢀmethylphenyl)propionic
1
acid anilide, m.p. 175—176 °C. H NMR, δ: 2.26 (s, 3 H, Me);
4.09, 4.94 (both d, 1 H each, H(2), H(3), J = 2.8 Hz); 7.07
(dd, 1 H, HPh(4), J1 = J2 = 7.8 Hz); 7.12 (d, 2 H, HAr(3)
and HAr(5), J = 7.9 Hz); 7.29 (d, 2 H, HPh(2) and HPh(6),
J = 8.0 Hz); 7.31 (dd, 2 H, HPh(3) and HPh(5), J1 = 7.8,
J2 = 8.0 Hz); 7.64 (d, 2 H, HAr(2) and HAr(6), J = 7.9 Hz); 9.52

2864
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 12, December, 2015
Mamedov et al.
3ꢀ(4ꢀNitrophenyl)quinolinꢀ2(1H)ꢀone (4d) was synthesized
similarly to compound 4e (see below) following the known
procedure.16
References
1. O. Rosen, in Comprehensive Organic Synthesis, Ed. B. M.
Trost, I. Fleming, C. H. Heathcock, Pergamon, Oxford,
1991, v. 2, p. 409.
2. V. A. Mamedov, I. A. Litvinov, O. N. Kataeva, I. Kh. Rizꢀ
vanov, I. A. Nuretdinov, Monatsh. Chem., 1994, 125, 1427.
3. T. Hirashita, K. Kinoshita, H. Yamamura, M. Kawai,
S. Araki, J. Chem. Soc., Perkin Trans. 1, 2000, 825.
4. Y. Shinohara, Y. Ohba, R. Takagi, S. Koijma, K. Ohkata,
Heterocycles, 2001, 55, 9.
5. F. A. Davis, Y. Wu, Y. Yan, W. McCoull, K. R. Prasad,
J. Org. Chem., 2002, 68, 2410.
6. V. A. Mamedov, E. A. Berdnikov, S. Tsuboi, H. Hamamoto,
T. Komiyama, E. A. Gorbunova, A. T. Gubaidullin, I. A.
Litvinov, Russ. Chem. Bull. (Int. Ed.), 2006, 55, 1455 [Izv.
Akad. Nauk, Ser. Khim., 2006, 1402].
7. S. Bodforss, Ber. Chem. Ges., 1919, 52, 142.
8. R. Imashiro, T. Yamanaka, M. Seki, Tetrahedron: Asymꢀ
metry, 1999, 10, 2845.
9. V. A. Mamedov, I. A. Nuretdinov, 1992, 41, 1690 [Izv. Akad.
Nauk, Ser. Khim., 1992, 2159].
10. V. K. Aggarwal, G. Hynd, W. Picoul, J.ꢀL. Vasse, J. Am.
Chem. Soc., 2002, 124, 9964.
3ꢀ(4ꢀTrifluoromethylphenyl)quinolinꢀ2(1H)ꢀone (4e) was synꢀ
thesized under previously described conditions16 by treatment of
2,3ꢀepoxyꢀ3ꢀ(4ꢀtrifluoromethylphenyl)propionic acid anilide
(1e) (0.51 g, 1.67) with a solution of H2SO4 in dimethyl sulfate.
Yield 0.08 g (89%), m.p. 249—250 °C. Found (%): C, 66.32;
H, 3.52; F, 19.92; N, 4.89. C16H10F3NO. Calculated (%): C, 66.44;
H, 3.48; F, 19.70; N, 4.84. IR, ν/cm–1: 1664. 1H NMR, δ: 7.22,
7.54 (both dd, 1 H each, HQ(6), HQ(7), J1 = 7.4 Hz, J2 = 7.6 Hz,
J3 = 7.4 Hz, J4 = 8.2 Hz); 7.36, 7.51 (both d, 1 H each, HQ(5),
HQ(8), J = 8.2 Hz, J = 7.6 Hz); 7.28, 7.99 (both d, 2 H each,
H(2), H(6) and H(3), HAr(5), J = 8.2 Hz); 8.22 (s, =CH); 12.03
(br.s, NH).
Reactions of 3ꢀarylꢀ2ꢀbromoꢀ3ꢀhydroxypropionic acid anilꢀ
ides 3d,e with H2SO4 carried out under previously described
conditions16 led to hardly separable mixtures, whose 1H NMR
spectra did not contain signals characteristic of 3ꢀarylquinolinꢀ
2(1H)ꢀones. In the case of 3e, we succeeded in isolation of
2ꢀbromoꢀ3ꢀ(4ꢀnitrophenyl)acrylic acid Nꢀ(4ꢀmethoxysulfonylꢀ
phenyl)amide (5) by recrystallization from chloroform.
2ꢀBromoꢀ3ꢀ(4ꢀnitrophenyl)acrylic acid Nꢀ(4ꢀmethoxysulfonꢀ
ylphenyl)amide (5). Yield 17%, m.p. 143—145 °C. Found (%):
C, 43.63; H, 2.72; Br, 17.58; N, 6.18; S, 7.11. C16H13BrN2O6S.
Calculated (%): C, 43.55; H, 2.97; Br, 18.11; N, 6.35; S, 7.27.
IR, ν/cm–1: 878, 1140, 1180, 1575, 1658, 1703, 3315. 1H NMR,
δ: 3.83 (s, 3 H, OMe); signals of the 4 MeOC6H4SO2 and
4ꢀO2NC6H4 moieties: 7.78 (d, 2 H, H(3), H(5), J = 8.7 Hz), 7.85
(d, 2 H, H(3), H(5), J = 8.5 Hz), 7.92 (d, 2 H, H(2), H(6),
J = 8.5 Hz), 8.22 (d, 2 H, H(2), H(6), J = 8.7 Hz); 10.51 (br.s,
1 H, NH).
11. S. Tosaki, R. Tsuji, T. Ohshima, M. Shibasaki, J. Am. Chem.
Soc., 2005, 127, 2147.
12. V. K. Aggarwal, J. P. H. Charmant, D. Fuentes, J. N. Harꢀ
vey, G. Hynd, D. Ohara, W. Picoul, R. Robiette, C. Smith,
J.ꢀL. Vasse, C. Winn, J. Am. Chem. Soc., 2006, 128, 2105.
13. D. Diez, M. G. Nunez, A. B. Anton, P. Garcia, R. F. Moro,
N. M. Carido, I. S. Marcos, P. Basabe, J. G. Urones, Curr.
Org. Synthesis, 2008, 5, 186.
14. W.ꢀJ. Liu, B.ꢀD. Lv, L.ꢀZ. Gong, Angew. Chem., Int. Ed.
Engl., 2009, 48, 6503.
15. Y. Kobayashi, T. Harayama, Org. Lett., 2009, 11, 1603.
16. V. A. Mamedov, V. L. Mamedova, S. F. Kadyrova, G. Z.
Khikmatova, A. T. Gubaidullin, I. Kh. Rizvanov, Sh. K.
Latypov, Tetrahedron, 2015, 71, 2670.
17. R. P. Srivastava, J. K. Zjawiony, J. R. Peterson, J. D.
McChesney, Tetrahedron: Asymmetry, 1994, 5, 1683.
18. H. Hamamoto, V. A. Mamedov, M. Kitamoto, N. Hayashi,
S. Tsuboi, Tetrahedron: Asymmetry, 2000, 11, 4485.
19. A. S. Dneprovskii, T. I. Temnikova, Teoreticheskie osnovy
organicheskoi khimii [Fundamentals of Organic Chemistry],
Khimiya, Leningrad, 1979, p. 289, 334 (in Russian).
20. APEX2 (Version 2.1), SAINTPlus. Data Reduction and Corꢀ
rection Program (Version 7.31A), Bruker Advansed Xꢀray
Solutions/BrukerAXS Inc., Madison, Wisconsin, USA, 2006.
21. G. M. Sheldrick, SADABS, Program for empirical Xꢀray abꢀ
sorption correction, BruukerꢀNonius, 1990—2004.
22. G. M. Sheldrick, SHELXLꢀ97, Program for Cristal Structure
Refinement, University of Goetingen. Germani, 1997.
23. L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
24. A. L. Spek, Acta Crystallogr. Sect. A, 1990, 46, 34.
25. I. J. Bruno, J. C. Cole, P. R. Edgington, M. K. Kessler, C. F.
Macrae, P. McCabe, J. Pearson, R. Taylor, Acta Crystallogr.
Sect. A, 2002, 58, 389.
3ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀoxopropanoic acid anilide (6). Methꢀ
od A. Compound 6 was synthesized as above by treatment of
anilide 1f with hydrobromic acid. Yield 0.26 g (97%).
Method B. To anilide 1f (0.45 g, 1.67 mmol), a mixture of
dimethyl sulfate (4 mL) and concentrated H2SO4 (1 mL) was
added. The reaction mixture was heated at 100 °C for 5 h, then
cooled to room temperature and poured into water. The precipꢀ
itate formed was collected by filtration and washed with acetone.
The removal of the volatiles from the filtrate afforded compound 6
in the yield 0.32 g (72%). M.p. 124 °C. Found (%): C, 71.42;
H, 5.58; N, 5.50. C16H15NO3. Calculated (%): C, 71.36; H, 5.61;
N, 5.20. IR, ν/cm–1: 757, 1256, 1519, 1536, 1604, 1668, 1724,
3335. 1H NMR, δ, keto form: 3.72 (s, 3 H, OMe); 4.17 (s, 2 H,
CH2); 6.88 (d, 2 H, HAr(3) and HAr(5), J = 8.3 Hz); 7.12 (dd, 1 H,
HPh(4), J1 = J2 = 7.4 Hz); 7.17 (d, 2 H, HAr(2) and HAr(6),
J = 8.3 Hz); 7.34 (dd, 2 H, HPh(3) and HPh(5), J1 = J2 = 7.8 Hz);
7.77 (d, 2 H, HPh(2) and HPh(6), J = 7.9 Hz); 10.45 (s, 1 H, NH);
enol form: 3.76 (s, 3 H, OMe); 6.47 (s, 1 H, CH=); 6.94 (d, 2 H,
HAr(3) and HAr(5), J = 8.5 Hz); 7.09 (dd, 1 H, HPh(4), J1 = J2 =
= 7.8 Hz); 7.15 (d, 2 H, H(2), H(6), J = 8.5); 7.34 (dd, 2 H, HPh(3)
and HPh(5), J1 = J2 = 7.8 Hz); 7.77 (d, 2 H, HPh(2) and HPh(6),
J = 7.2 Hz); 10.02 (s, 1 H, NH); the ratio of keto : enol = 1 : 0.3.
MS, m/z: 270.1146 [M + H]+. Calculated: [M + H]+ 270.1125.
This work was financially supported by the Russian
Science Foundation in the research priority area "Basic
scientific research and exploratory scientific research conꢀ
ducted by the existing research laboratories (departments)"
(Project No. 14ꢀ23ꢀ00073).
Received May 22, 2015;
in revised form September 21, 2015