Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
1070-3632
Synthesis and Structure (Z)-N-Aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides
V. L. Gein 1
T. M. Zamaraeva 1
E. V. Gorgopina 1
N. M. Igidov 1
O. V. Bobrovskaya 1
M. V. Dmitriev 0
0 Perm State National Research University , Perm , Russia
1 Perm State Pharmaceutical Academy , ul. Polevaya 2, Perm, 614990 Russia
-Reactions of 5-phenyl-2,3-dihydrofuran-2,3-dione with aromatic amines in anhydrous dioxane or methyl benzoylpyruvate with aromatic amines in the presence of sodium acetate in glacial acetic acid afforded (Z)-N-aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides. Aroylpyruvic acid amides are of obvious chemical interest. These polyfunctional reagents show high reactivity due to the presence of several reaction sites in their structure [1, 2]. They can act as C-nucleophiles and carbonyl electrophiles in the reactions, being promising starting materials for the synthesis of a variety of acyclic and heterocyclic compounds [1-4]. R = С6H5 (1), 4-BrС6H4 (2), 4-IС6H4 (3), 3-ClС6H4 (4), 4-C2H5OOCС6H4 (5), 4-CH3С6H4 (6), 4-CH3OС6H4 (7), 4-NH2SO2С6H4CH2CH2 (8).
methyl benzoylpyruvate; 5-phenyl-2; 3-dihydrofuran-2; 3-dione; arylamines; aroylpyruvic acid amides
-
The most studied method for the preparation of
N-substituted amides of aroylpyruvic acids is the ring
opening of 5-aryl-2,3-dihydrofuran-2,3-diones under
the action of N-nucleophiles in an inert solvent
medium with an equimolar ratio of the reagents [5, 6].
Because of a number of drawbacks in this method [7],
it remains urgent to find optimal conditions for the
synthesis of amides of aroylpyruvic acids, which due
to widely varying pharmacophore groups in their
structure can be used further in the preparation of
previously unknown and inaccessible functional
heterocyclic compounds.
A new simple method for the preparation of
Narylamides of aroylpyruvic acids reported in [8]
includes the reaction of arylamines with methyl
aroylpyruvates in acetic acid in the presence of
anhydrous sodium acetate. Later, arylamides obtained
have been modified with
4-aminobenzenesulfonylacetamide sodium (sodium sulfacetamide) [9],
4-aminobenzenesulfonylguanidine (sulgine) [10], streptocide,
and norsulfazole fragments [11].
Ph
Ph
O
O
O
O
O
OH
+ NH2R
O
+ NH2R
CH3COONa
O
OH
A
1_8
N
H
R
Ph
O
O
B
O
N
H
R
Scheme 1.
Ph
O
Continuing research in this direction, we apply this
method for the synthesis of new N-arylamides of
aroylpyruvic acids and studied their spatial structure.
For the comparative study,
(Z)-N-aryl-2-hydroxy-4oxo-4-phenylbut-2-enamides were prepared by reacting
5-phenyl-2,3-dihydrofuran-2,3-dione with anilines in an
anhydrous dioxane.
To establish the possibility of using alkylamines in
the synthesis of aroylpyruvic acid amides, we
performed the reaction with 4-(2-aminoethyl)
benzenesulfonamide by two aforementioned methods.
However, we did not succeed in obtaining compound 8
according to method b.
Compounds 1–8 are yellow crystalline substances
soluble in DMF, DMSO, soluble at heating in acetic
acid, ethanol, and insoluble in water (Scheme 1).
In the 1H NMR spectra of compounds 1–8, there
were singlets of COCH2CO (4.53–4.64 ppm), CH=
(7.02–7.17 ppm), CONH groups (8.99–10.78 pm), as
well as the signals of aromatic fragments. In the
spectrum of 8, the protons of both CH2 and NH2
groups were recorded in the regions of 2.86–3.51 and
7.32 ppm, respectively.
Crystal structure of compound 5 was studied by
single-crystal X-ray diffraction method (see the
figure). The crystals were obtained by slow
crystallization from acetic acid. The molecule of 5
crystallizes in the centrosymmetric spatial group of the
monoclinic crystal system. The molecule is practically
planar. The electron density of the keto-enol fragment
is strongly delocalized, which is expressed in
equalizing the lengths of multiple and single C–C and
C–O bonds (see Table). The position of the hydrogen
atom of the enol hydroxy group was refined taking into
account the disordering due to the existence of
tautomeric equilibrium [the ratio of the populations of
the H4 and H5 atoms is 0.59(
7
) to 0.41(
7
),
respectively]. In addition to the intramolecular hydrogen
bond in the keto-enol fragment the molecule also has
an intramolecular hydrogen bond of non-classical type
С6–H6···O3 [H6···O3 2.329, С6···O3 2.927(
4
) Å]. The
crystal packing is stabilized by van der Waals
interactions and several shortened С–H···O contacts.
According to the studies performed, the most
effective and convenient method for the synthesis of
(Z)-N-aryl-2-hydroxy-4-oxo-4-phenylbut-2-enamides
containing arylamine fragment with an
electronwithdrawing group is the reaction of benzoylpyruvic
acid methyl ester with arylamines in glacial acetic acid
General view of the molecule of compound 5 in the crystal
represented by thermal ellipsoids with 50% probability.
in the presence of anhydrous sodium acetate. When
using an aromatic amine with an electron-donor
substituent or an alkyla (...truncated)