Iminofurans chemistry: IV. Synthesis and structure of 2-N-aryl-substituted derivatives of 2-amino-4-aryl-4-oxobut-2-enoic and 2-amino-5,5-dimethyl-4- oxohex-2-enoic acids

Article abstract of DOI:10.1134/S1070428009050091

Reactions of arylamines with 4-aryl-2-hydroxy-4-oxobut-2-enoic and 2-hydroxy-5,5-dimethyl-4-oxohex-2-enoic acids gave rise to 4-aryl-2-arylamino-4- oxobut-2-enoic and 2-aryl-amino-5,5-dimethyl-4-oxohex-2-enoic acids that existed in solutions as Z- and E-i

Full text of DOI:10.1134/S1070428009050091

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 698−702. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.M. Igidov, A.E. Rubtsov, A.V. Tyuneva, V.V. Zalesov, A.Yu. Borodin, E.V. Bukanova, 2009, published in Zhurnal Organicheskoi
Khimii, 2009, Vol. 45, No. 5, pp. 716−721.
Iminofurans Chemistry: IV.* Synthesis and Structure
of 2-N-Aryl-Substituted Derivatives of 2-Amino-4-aryl-4-oxobut-2-
enoic and 2-Amino-5,5-Dimethyl-4-oxohex-2-enoic Acids
N. M. Igidovb, A. E. Rubtsova, A. V. Tyunevaa, V. V. Zalesova,
A. Yu. Borodinb, and E. V. Bukanovab
aPerm State University, Perm, 614990 Russia,
e-mail: Aleksandr.Rubtsov@psu.ru
b Perm State Pharmaceutical Academy, Perm, Russia
Received June 19, 2008
Abstract—Reactions of arylamines with 4-aryl-2-hydroxy-4-oxobut-2-enoic and 2-hydroxy-5,5-dimethyl-4-oxohex-
2-enoic acids gave rise to 4-aryl-2-arylamino-4-oxobut-2-enoic and 2-aryl-amino-5,5-dimethyl-4-oxohex-2-enoic
acids that existed in solutions as Z- and E-isomers or in a ring form as 3-arylamino-5-tert-butyl-5-hydroxyfuran-
2(5H)-ones. The probable cyclization mechanism of these compounds into 5-R-3-arylimino-3H-furan-2-one
derivatives was considered.
DOI: 10.1134/S1070428009050091
the factors governing this process but first of all the
establishment of the fine structure of acids II. To this
end we synthesized a series of previously unknown
N-substituted 2-amino-4-aryl-4-oxobut-2-enoic acids IIa–
IIn and N-substituted 2-amino-5,5-dimethyl-4-oxohex-2-
enoic acids IIIa–IIIk. The choice of the amino com-
pounds was not only based on the chemical targets but
also on the possibility to obtain biologically active
substances proceeding from 4-aryl-2-hydroxy-4-oxobut-
2-enoic acids (aroylpyruvic acids) Ia–Ig [3–7] and 2-
hydroxy-5,5-dimethyl-4-oxohex-2-enoic acid.
We showed formerly that N-substituted 2-amino-4-
aryl-4-oxobut-2-enoic acids under the treatment with
acetic anhydride underwent a cyclization into N-sub-
stituted 5-aryl-3-imino-3H-furan-2-ones [2]. The synthetic
method proved to be fairly general, and using it we
prepared a wide range of iminofuranones with various
substituents both at the imine nitrogen and in the position
5 of the furan ring. However in some events we failed to
isolate iminofurans either because the initial acids did not
undergo cyclization under the reaction conditions or since
the formed iminofuranones were very labile compounds.
First from acids Ia–Ig and aromatic amines N-aryl
derivatives of 2-amino-4-aryl-4-oxobut-2-enoic acids IIa–
IIn were obtained in 63–91% yields. Compound IIj
obtained in 44% yield was an exclusion (Scheme 1).
In the IR spectra of compounds IIa–IIn recorded
from mulls in mineral oil a pronounced absorption band
of NH group was observed in the region 3192–3256 cm–1
(compounds IIa–IId, IIh–IIk, IIm, IIn); in some com-
pounds appeared a plateau in the region 3100–3150 cm–1
(compounds IIf and IIl)] or this band was totally absent
(compounds IIe and IIg). The absorption band of the
carboxy group of compounds IIa, IIb, IIe, IIf, IIg was
present in the region 1700–1731 cm–1, and the strong
combined band of the stretching vibrations of the ester
The investigation of the cyclization mechanism of acids
II into iminofuranones requires not only elucidation of
* For communication III, see [1].
698

IMINOFURANS CHEMISTRY: IV.
699
Scheme 1.
I, R = H (a), F (b), Br (c), Cl (d), Me (e), MeO (f), EtO (g); II, R = H,Ar = 2,4-Me2C6H3 (a), 2,6-Me2C6H3 (b), 2,4,6-Me3C6H2 (c),
3-CF3C6H4 (d), 2-Me-5-NO2C6H3 (e), 4-Et2N(CH2)2OOCC6H4 (f); R = Me,Ar = 2-Me-5-NO2C6H3 (g);Ar = 4-EtOOCC6H4, R =
H (h), F (i), Br (j), Cl (k), Me (l), MeO (m), EtO (n).
and the carboxy groups of compounds IIf, IIh, IIj, IIk,
IIm, IIn was observed in the region 1711–1729 cm–1.
Compounds IIi and IIl formed an exclusion, since in their
IR spectra individual bands were present corresponding
to the stretching vibrations of the ester and the carboxy
groups in the region 1709, 1707 and 1727, 1726 cm–1.
Besides in the IR spectra of compounds IIc and IId the
absorption band of the carboxy group was absent but
a shoulder was present in the region 1645 and 1661 cm–1
respectively, presumably because these compounds
existed in the form C.
In the IR spectra of compounds IIIa–IIIk recorded
from mulls in mineral oil appeared one (compounds IIIa–
IIIe, IIIi, in the region 3228–3256 cm–1) or two
(compounds IIIf, IIIj, in the region 3198–3375 cm–1)
absorption bands of the NH group. These bands are
lacking in the spectra of compounds IIIg, IIIh, IIIk.
The carboxy group absorption band of compounds IIIc,
IIIg–IIIi is observed in the region 1670–1712 cm–1 (in
the spectrum of compound IIIk a combined band is
present in the region 1712 cm–1). In the spectra of com-
pounds IIIa, IIIb, IIId–IIIf the carboxy group gives
rise to two absorption bands in the regions 1690–1748
and 1665–1680 cm–1.
1H NMR spectra of compounds IIIa–IIIc, IIIe, IIIk
show that they exist in DMSO-d6 in two enamino-ketone
forms A (Z-isomer) and B (E-isomer), with the content
of the Z-isomer 47–83%. Z-Isomer (form A) is
characterized by the presence in the spectrum of vinyl
proton signals at 5.66–6.52 ppm and of the NH group
proton at 10.99–12.00 ppm. In the spectrum of Ε-isomer
(form B) the signal of vinyl proton appeared at 4.88–
5.41 ppm, and the signal of NH group proton at 9.65–
9.67 ppm we succeeded to detect only in the spectra of
compounds IIIa–IIIc. We failed to find in the spectra
the signal of the OH group proton apparently due to
significant broadening.
We studied the 1H NMR spectra of compounds IIa–
IIn and established that compounds IId, IIe, IIj, IIl,
and IIn possessing electron-withdrawing substituents in
the aromatic ring linked to the nitrogen atom existed in
the DMSO-d6 solution in one enamino-ketone form as
Z-isomer (form A) as confirmed by the presence of one
singlet from a vinyl proton at 6.53– 7.03 ppm and a proton
signal from the NH group at 11.72–11.81 ppm. In contrast,
1
as showed the H NMR spectra, compounds IIa–IIc
containing only electron-donor substituents at the aromatic
ring existed in DMSO-d6 in the form of two enamino-
ketone isomers: A (Z-isomer) and B (E-isomer), the
content of Z-isomer varying in the range 50–100%. The
proton signal of the NH group of the Z-isomer of
compounds IIb and IIc appeared at 11.54–11.98 ppm.
We failed to find in the spectra the signal of the OH group
proton apparently due to significant broadening.
1
According to H NMR spectra of compounds IIId,
IIIf–IIIh, IIIj the fraction of the Z-isomer (form A)
amounted to 22–82%. The signals of protons belonging
to Ε-isomer are absent in the solution, but proton signals
are observed corresponding to the 3-arylamino-5-tert-
Further from the 2-hydroxy-5,5-dimethyl-4-oxohex-2-
enoic acid and arylamines we obtained 2-arylamino-5,5-
dimethyl-4-oxohex-2-enoic acids IIIa–IIIk.
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IGIDOV et al.
700
Scheme 2.
butyl-5-hydroxyfuran-2(5H)-ones (cyclic form D). Form
D was characterized by the presence in the spectrum of
a singlet from vinyl proton at 6.38–6.49 ppm and of
a broadened proton signal from the alcoholic hydroxy
group at 6.73–7.24 ppm. The signal of the NH group
proton of compounds IIIf, IIIj appeared at 8.49, 8.68
ppm respectively, and of compounds IIId, IIIg, IIIh, in
the region of aromatic protons. 5-tert-Butyl-5-hydroxy-
3-(4-ethoxycarbonylphenylamino)furan-2(5H)-one was
obtained previously and characterized in [8]. However
we failed to isolate this cyclic form of compounds III as
individual substances.
of the molecule it is possible if not to achieve the formation
of Z-enimino-enol form E of compounds II, then to have
a sufficiently strong intramolecular hydrogen bond
favoring the formation of such Z-enimino-enol structure
at insignificant energy supply.
This suggestion is confirmed not only by published
data [9] but also by the formation of 3-(4-ethoxycarbonyl-
phenyl)imino-5-(4-ethoxyphenyl)-3H-furan-2-one (IV) at
heating compound IIn at 140°C. Compound IIn unlike
compounds IIa–IIm eliminated water at heating providing
compound IV. The latter was also obtained by intra-
molecular cyclization of compound IIn in acetic anhydride.
We established that acids Ia–Ig and 2-hydroxy-5,5-
dimethyl-4-oxohex-2-enoic acid did not react with the
sterically hindered 2,6-dibromo-4-chloroaniline, 3,5-di-
methyl-2,6-dicyanoaniline, and 4,6-dibromo-2-{[cyclo-
hexyl(methyl)amino]methyl}aniline (the base of a drug
bromhexine).
It is not inconceivable that a similar heterocyclization
through form E may occur also with compounds III
although in the latter case the cyclization mechanism
through intermediate furanones D by water elimination
also seems possible.
The spectral characteristics of compounds II show
that at introducing electron-withdrawing substituents into
the aromatic ring attached to the nitrogen and electron-
donor substituents to the aromatic ring in the aroyl part
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
FSM-1201 from mulls in mineral oil. 1H NMR spectra
were registered on spectrometers Bruker DRX-500
(500.13 MHz) and Varian Mercury Plus-300 (300.05
MHz) in DMSO-d6 and CDCl3, internal reference
HMDS. The reaction progress was monitored and the
purity of compounds obtained was checked by TLC on
Silufol UV-254 or Sorbfil plates, eluent ether–benzene–
acetone, 10:9:1, spots were visualized under iodine vapor.
O
HO
HO
150oC
N
IIn
Ar
Ar
E
4-Aryl-2-arylamino-4-oxobut-2-enoic acids IIa–
IIn. To a solution of 0.01 mol of 4-aryl-2-hydroxy-4-
oxobut-2-enoic acid Ia–Ig in 20 ml of ethanol was added
a solution of 0.01 mol of amine in 20 ml of ethanol, and
the mixture was left standing for 24 h at 20–25°C. The
O
Ar
O
Ac2O
IIn
_
_
H2O
2AcOH
N Ar
IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

IMINOFURANS CHEMISTRY: IV.
701
mixture was cooled to 0°C, the separated precipitate was
filtered off and recrystallized.
2-[4-(2-N,N-Diethylaminoethoxycarbonyl)-
phenylamino]-4-oxo-4-phenylbut-2-enoic acid (IIf).
Yield 3.28 g (80%), yellow crystals, mp 207.5–209.5°C
(i-PrOH). IR spectrum, ν, cm–1: 3150 sh (NH), 1713
2-(2,4-Dimethylphenylamino)-4-oxo-4-phenyl-
but-2-enoic acid (IIa). Yield 2.01 g (68%), yellow
crystals, mp 180–181°C (benzene–hexane). IR spectrum,
1
(COOH, COOEt). H NMR spectrum, δ, ppm, form A
(80%): 1.20 group of signals (6H, Me), 3.12 q (4H, 2CH2),
3.37 group of signals (2H, CH2), 3.42 group of signals
(2H, CH2), 5.97 s (1H, CH), 7.2–7.9 m (9H, Ph, C6H4),
12.48 s (1H, NH); form B (20%): 1.20 group of signals
(6H, Me), 3.12 q (4H, 2CH2), 3.37 group of signals (2H,
CH2), 3.42 group of signals (2H, CH2), 5.20 s (1H, CH),
7.2–7.9 m (9H, Ph, C6H4), 9.80 s (1H, NH). Found, %:
C 67.32; H 6.42; N 6.80. C23H26N2O5. Calculated, %:
C 67.30; H 6.38; N 6.82.
1
ν, cm–1: 3256 (NH), 1730 (COOH). H NMR spectrum,
δ, ppm, form A (76%): 2.27 s (6H, Me), 6.29 s (1H, CH),
6.76–7.92 m (8H, Ph, C6H3), 11.98 s (1H, NH); form B
(24%): 2.16 s (6H, Me), 5.62 s (1H, CH), 6.76–7.92 m
(8H, Ph, C6H3), 9.90 s (1H, NH). Found, %: C 73.28;
H 5.73; N 4.81. C18H17NO3. Calculated, %: C 73.20;
H 5.80; N 4.74.
2-(2,6-Dimethylphenylamino)-4-oxo-4-phenyl-
but-2-enoic acid (IIb). Yield 1.71 g (58%), yellow
crystals, mp 164-165°C (benzene–hexane). IR spectrum,
2-(2-Methyl-5-nitrophenylamino)-4-(4-methyl-
phenyl)-4-oxobut-2-enoic acid (IIg), form A. Yield
2.58 g (76%), yellow crystals, mp 176–177°C (i-PrOH).
IR spectrum, ν, cm–1: 1731 (COOH). 1H NMR spectrum,
δ, ppm: 2.31 s (3H, Me), 2.37 s (3H, Me), 6.46 s (1H,
CH), 6.92–7.82 m (7H, C6H4, C6H3), 11.83 s (1H, NH).
Found, %: C 63.59; H 4.78; N 8.19. C18H16N2O5.
Calculated, %: C 63.52; H 4.74; N 8.23.
1
ν, cm–1: 3192 (NH), 1700 (COOH). H NMR spectrum,
δ, ppm, form A (63%): 2.19 s (6H, 2Me), 6.29 s (1H,
CH), 7.01–7.92 m (8H, Ph, C6H3), 11.60 s (1H, NH);
form B (24%): 2.16 s (6H, 2Me), 5.26 s (1H, CH), 7.01–
7.92 m (8H, Ph, C6H3), 9.90 (1H, NH), 11.60 s (1H, NH).
Found, %: C 73.31; H 5.86; N 4.77. C18H17NO3.
Calculated, %: C 73.20; H 5.80; N 4.74.
4-Oxo-4-(4-fluorophenyl)-2-[N-(4-ethoxy-
carbonylphenyl)]aminobut-2-enoic acid (IIh), form
A. Yield 3.14 g (88%), yellow crystals, mp 148–149°C
(toluene). IR spectrum, ν, cm–1: 3194 (NH), 1709, 1727
4-Oxo-2-(2,4,6-trimethylphenylamino)-4-phenyl-
but-2-enoic acid (IIc). Yield 2.75 d (89%), yellow
crystals, mp 187–189°C (i-PrOH). IR spectrum, ν, cm–1:
1
3200 (NH), 1645 sh (COOH). H NMR spectrum, δ,
1
(COOH, COOEt). H NMR spectrum (CDCl3), δ, ppm:
ppm, form A(64%): 2.11–2.20 group of signals (9H, 3Me),
6.24 s (1H, CH), 6.83–7.91 m (7H, Ph, C6H2), 11.54 s
(1H, NH); form B (36%): 2.11– 2.20 group of signals
(9H, 3Me), 5.29 s (1H, CH), 6.83–7.91 m (7H, Ph, C6H2),
9.85 s (1H, NH). Found, %: C 73.69; H 6.24; N 4.59.
C19H19NO3. Calculated, %: C 73.77; H 6.19; N 4.53.
1.41 t (3H, CH3CH2), 4.33 q (2H, CH3CH2), 6.71 s (1H,
CH), 7.04–8.14 m (8H, 2C6H4), 8.90 s (1H, NH). Found,
%: C 63.85; H 4.53; N 3.93. C19H16FNO5. Calculated,
%: C 63.86; H 4.51; N 3.92.
4-(4-Bromophenyl)-4-oxo-2-[N-(4-ethoxy-
carbonylphenyl)]aminobut-2-enoic acid (IIj), formA.
Yield 1.84 d (44%), yellow crystals, mp 144–146°C
(MeCN). IR spectrum, ν, cm–1: 3204 (NH), 1719
4-Oxo-2-(3-trifluoromethylphenylamino)-4-
phenylbut-2-enoic acid (IId), form A. Yield 2.70 g
(81%), yellow crystals, mp 168–169°C (EtOH). IR
1
(COOH, COOEt). H NMR spectrum, δ, ppm: 1.23 t
1
spectrum, ν, cm–1: 3244 (NH), 1661 (COOH). H NMR
(3H, CH3CH2), 4.22 q (2H, CH3CH2), 7.03 s (1H, CH),
7.65 m (8H, 2C6H4), 11.76 s (1H, NH). Found, %: C 54.59;
H 3.88; N 3.39. C19H16BrNO5. Calculated, %: C 54.56;
H 3.86; N 3.35.
spectrum, δ, ppm: 6.48 s (1H, CH), 7.42–7.94 m (9H,
Ph, C6H4), 11.66 s (1H, NH). Found, %: C 60.94; H 3.62;
N 4.19. C17H12F3NO3. Calculated, %: C 60.90; H 3.61;
N 4.17.
4-Oxo-4-(4-chlorophenyl)-2-[N-(4-ethoxy-
carbonylphenyl)]aminobut-2-enoic acid (IIk). Yield
2.91 g (78%), yellow crystals, mp 154–156°C (MeCN)
(mp 177–178°C [10]). IR spectrum, ν, cm–1: 3204 (NH),
1722 (COOH, COOEt). Found, %: C 61.09; H 4.34;
N 3.79. C19H16ClNO5. Calculated, %: C 61.05; H 4.31;
N 3.75.
2-(2-Methyl-5-nitrophenylamino)-4-oxo-4-
phenylbut-2-enoic acid (IIe), form A. Yield 2.74 g
(84%), yellow crystals, mp 185–186°C (i-PrOH). IR
1
spectrum, ν, cm–1: 1731 (COOH). H NMR spectrum,
δ, ppm: 2.38 s (3H, Me), 6.49 s (1H, CH), 7.38–7.90 m
(8H, Ph, C6H3), 11.81 s (1H, NH). Found, %: C 62.51;
H 4.38; N 8.67. C17H14N2O5. Calculated, %: C 62.57;
H 4.32; N 8.59.
4-(4-Methylphenyl)-4-oxo-2-[N-(4-ethoxy-
carbonylphenyl)]aminobut-2-enoic acid (IIl), formA.
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IGIDOV et al.
702
1
ν, cm–1: 3256 (NH), 1690, 1670 (COOH). H NMR
spectrum, δ, ppm, form A (59%): 1.13 s (9H, CMe3),
2.05–2.21 group of signals (6H, 2Me), 5.71 s (1H, CH),
6.89–7.11 m (3H, C6H3), 11.05 br.s (1H, NH); form B
(48%): 1.13 s (9H, CMe3), 2.05–2.21 group of signals
(6H, 2Me), 4.88 s (1H, CH), 6.89–7.11 m (3H, C6H3),
9.67 br.s (1H, NH). Found, %: C 69.73; H 7.74;
N 5.01. C16H21NO3. Calculated, %: C 69.79; H 7.69;
N 5.09.
Yield 2.93 g (83%), yellow crystals, mp 155–156°C
(MeCN). IR spectrum, ν, cm–1: 3100 (NH), 1707, 1726
1
(COOH, COOEt). H NMR spectrum, δ, ppm: 1.26 t
(3H, CH3CH2), 2.33 s (3H, CH3C6H4), 4.23 q (2H,
CH3CH2), 6.53 s (1H, CH), 7.50 m (8H, 2C6H4), 11.75 s
(1H, NH). Found, %: C 67.96; H 5.48; N 3.92.
C20H19NO5. Calculated, %: C 67.98; H 5.42; N 3.96.
4-(4-Methoxyphenyl)-4-oxo-2-[N-(4-ethoxy-
carbonylphenyl)]aminobut-2-enoic acid (IIm), form
A. Yield 3.17 g (86%), yellow crystals, mp 159–160°C
(MeCN). IR spectrum, ν, cm–1: 3192 (NH), 1729
(COOH, COOEt). Found, %: C 65.06; H 5.18; N 3.72.
C20H19NO6. Calculated, %: C 65.03; H 5.18; N 3.79.
5,5-Dimethyl-2-(2,4,6-trimethylphenylamino)-4-
oxohex-2-enoic acid (IIIc). Yield 1.73 g (60%),
colorless crystals, mp 104–105°C (hexane). IR spectrum,
ν, cm–1: 3232 (NH), 1670 (COOH). 1H NMR spectrum,
δ, ppm, form A (52%): 1.12 s [9H, C(CH3)3], 2.04–
2.24 group of signals (9H, 3CH3), 5.66 s (1H,CH),
6.71 s, 6.92 s (2H, C6H2), 10.99 br.s (1H, NH); form B:
0.93 s [9H, C(CH3)3], 2.04–2.24 group of signals (9H,
3CH3), 4.90 s (1H, CH), 6.71 s, 6.92 s (2H, C6H2), 9.66
br.s (1H, NH). Found, %: C 70.64; H 8.09; N 4.78.
C17H23NO3. Calculated, %: C 70.56; H 8.01; N 4.84.
4-Oxo-2-[N-(4-ethoxycarbonylphenyl)]amino-4-
(4-ethoxyphenyl)but-2-enoic acid (IIn), form A. Yield
3.52 g (92%), yellow crystals, mp 150– 151°C (MeCN).
IR spectrum, ν, cm–1: 3114 (NH), 1726 (COOH,
COOEt). 1H NMR spectrum, δ, ppm: 1.28 m (6H,
CH3CH2OCO, CH3CH2O), 4.06 q (2H, CH3CH2O),
4.23 q (2H, CH3CH2OCO), 6.53 s (1H, CH), 7.50 m
(8H, 2C6H4), 11.72 s (1H, NH). Found, %: C 67.76;
H 5.56; N 3.62. C21H21NO6. Calculated, %: C 65.79;
H 5.52; N 3.65.
2-(2-Bromophenylamino)-5,5-dimethyl-4-
oxohex-2-enoic acid (IIId). Yield 3.10 g (95%),
colorless crystals, mp 143–145°C (i-PrOH). IR spec-
1
trum, ν, cm–1: 3328 (NH), 1728, 1672 (COOH). H NMR
2-Arylamino-5,5-dimethyl-4-oxohex-2-enoic
acids IIIa–IIIk. To a solution of 1.72 g (0.01 mol) of
2-hydroxy-5,5-dimethyl-4-oxohex-2-enoic acid in 15 ml
of ethanol (or benzene) was added a solution of 0.01 mol
of arylamine in 20–30 ml of ethanol, the mixture was
heated for 3–4 min and left standing for 24 h at 20–25°C.
The precipitate was filtered off and recrystallized.
spectrum, δ, ppm, form A (82%): 1.13 s (9H, CMe3),
5.95 s (1H, CH), 6.81–7.61 m (4H, C6H4), 11,26 br.s
(1H, NH); form D (18%): 0.98 s (9H, CMe3), 6.43 s
(1H, CH), 6.73 s (1H, OH), 6.81–7.61 m (5H, NH, C6H4).
Found, %: C 51.51; H 4.90; N 4.32. C14H16BrNO3.
Calculated, %: C 51.55; H 4.94; N 4.29.
5,5-Dimethyl-2-(2,4-dimethylphenylamino)-4-
oxohex-2-enoic acid (IIIa). Yield 1.84 g (67%), yellow
crystals, mp 129–130°C (benzene–hexane). IR spectrum,
2-(2-Iodophenylamino)-5,5-dimethyl-4-oxohex-
2-enoic acid (IIIe). Yield 2.83 g (76%), yellow crystals,
mp 145–146°C (i-PrOH). IR spectrum, ν, cm–1: 3336
(NH), 1728, 1673 (COOH). 1H NMR spectrum, δ, ppm,
form A (83%): 1.14 s (9H, CMe3), 5.94 s (1H, CH), 6.72–
7.80 m (4H, C6H4), 11.26 br.s (1H, NH); form B: 0.98 s
(9H, CMe3), 5.20 s (1H, CH), 6.7–7.80 m (4H, C6H4).
Found, %: C 45.12; H 4.38; N 3.68. C14H16INO3.
Calculated, %: C 45.06; H 4.32; N 3.75.
1
ν, cm–1: 3240 (NH), 1695, 1665 (COOH). H NMR
spectrum, δ, ppm, form A (76%): 1.12 s (9H, CMe3),
2.21 s (6H, 2Me), 5.73 s (1H, CH), 6.65–7.07 m (3H,
C6H3), 11.40 s (1H, NH); form B (24%): 0.96 s (9H,
CMe3), 2.21 s (6H, 2Me), 5.18 s (1H, CH), 6.65–7.07 m
(3H, C6H3), 9.65 s (1H, NH). Mass spectrum, m/z (Irel,
%): 275 (12.0) [M]+, 230 (5.0) [M – COOH]+, 218 (33)
[M – CMe3]+, 200 (7.5) [M – H2O – Me3C]+, 172 (100)
[M – H2O – Me3CCO]+, 144 (28) [M – H2O –Me3CCO –
CO]+, 57 (49) [Me3C]+. Found, %: C 69.85; H 7.63;
N 5.15. C16H21NO3. Calculated, %: C 69.79; H 7.69;
N 5.09.
2-(4-Bromophenylamino)-5,5-dimethyl-4-
oxohex-2-enoic acid (IIIf). Yield 2.67 g (82%), yellow
crystals, mp 127–128°C (i-PrOH). IR spectrum, ν, cm–1:
1
3316, 3375 (NH), 1748, 1680 (COOH). H NMR
spectrum, δ, ppm, form A (26%): 1.13 s (9H, CMe3),
5.90 s (1H, CH), 7.0 d (2H, C6H4), 7.48 d (2H, C6H4),
11.33 s (1H, NH); form D (74%): 0.98 s (9H, CMe3),
6.38 s (1H,CH), 7.11 s (1H, OH), 7.25 d (2H, C6H4),
7.43 d (2H, C6H4), 8.49 s (1H, NH). Mass spectrum,
5,5-Dimethyl-2-(2,6-dimethylphenylamino)-4-
oxohex-2-enoic acid (IIIb). Yield 2.01 g (73%), yellow
crystals, mp 128–129°C (benzene–hexane). IR spectrum,
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IMINOFURANS CHEMISTRY: IV.
703
m/z (Irel, %): 325 (6.0) [M]+, 282 (2.0) [M – COOH]+,
270 (28.0), 268 (28.5) [M – CMe3]+, 222 (50), 224 (55)
[M – H2O – Me3CCO]+, 196 (8.5) [M – H2O – Me3CCO –
CO]+, 189 (42.5) [M – Br – Me3C]+, 171 (19.0)
[BrC6H4NH]+, 157 (13), 155 (13) [BrC6H4]+, 143 (28)
[M – H2O – Me3CCO – Br]+, 85 (6) [Me3CCO]+, 57
(97) [Me3C]+. Found, %: C 51.49; H 4.98; N 4.23.
C14H16BrNO3. Calculated, %: C 51.55; H 4.94; N 4.29.
M 326.19.
(22%): 1.13 s (9H, CMe3), 1.43 t (3H, CH3CH2), 4.29 q
(2H, CH3CH2), 5.95 s (1H, CH), 6.94–7.87 m (4H,
C6H4), 11.20 s (1H, NH); form D (78%): 0.98 C (9H,
CMe3), 1.43 t (3H, CH3CH2), 4.29 q (2H, CH3CH2),
6.49 s (1H, CH), 7.24 s (1H, OH), 7.3–7.87 m (4H,
C6H4), 8.68 s (1H, NH). Found, %: C 63.87; H 6.68; N
4.24. C17H21NO5. Calculated, %: C 63.94; H 6.63;
N 4.19.
5,5-Dimethyl-2-[4-(2-N,N-diethylamino)-
ethoxycarbonylphenylamino]-4-oxohex-2-enoic acid
(IIIk). Yield 3.35 d (86%), yellow crystals, mp 203–
204°C (EtOH). IR spectrum, ν, cm–1: 1712 (COOH,
COOEt). 1H NMR spectrum, δ, ppm, form A (47%):
1.10 group of signals (15H, 5Me), 2.88–3.41 m (6H,
3CH2), 4.30 group of signals (2H, CH2), 6.52 s (1H,CH),
7.19–7.78 m (4H, C6H4), 12.00 s (1H, NH); form B
(53%): 1.10 group of signals (15H, 5Me), 2.88–3.41 m
(6H, 3CH2), 4.30 group of signals (2H, CH2), 5.41 s (1H,
CH), 7.19–7.78 m (4H, C6H4). Found, %: C 64.53;
H 7.79; N 7.25. C21H30N2O5. Calculated, %: C 64.59;
H 7.74; N 7.17.
2-(2,4-Dibromophenylamino)-5,5-dimethyl-4-
oxohex-2-enoic acid (IIIg). Yield 2.51 g (62%), yellow
crystals, mp 156–157°C (benzene–hexane). IR spectrum,
ν, cm–1: 1708 (COOH). 1H NMR spectrum, δ, ppm, form
A (81%): 1.18 s (9H, CMe3), 6.06 s (1H, CH), 6.85–
7.83 m (3H, C6H3), 11.37 s (1H, NH); form D (19%):
1.03 s (9H, CMe3), 6.47 s (1H,CH), 6.85–7.83 m (4H,
NH, C6H3), 7.10 s (1H, OH). Found, %: C 41.47; H
3.81; N 3.41. C14H15Br2NO3. Calculated, %: C 41.51;
H 3.73; N 3.46.
5,5-Dimethyl-2-(2,4-dichlorophenylamino)-4-
oxohex-2-enoic acid (IIIh). Yield 2.18 d (69%), yellow
crystals, mp 150–151°C (benzene–hexane). IR spectrum,
ν, cm–1: 1712 (COOH). 1H NMR spectrum, δ, ppm, form
A (69%): 1.15 s (9H, CMe3), 6.09 s (1H, CH), 7.02–
7.64 m (3H, C6H3), 11.46 s (1H, NH); form D (31%):
0.99 s (9H, CMe3), 6.41 s (1H, CH), 7.02–7.64 m (4H,
NH, C6H3), 7.18 s (1H, OH). Found, %: C 53.26; H 4.71;
N 4.49. C14H15Cl2NO3. Calculated, %: C 53.18; H 4.78;
N 4.43.
3-(4-Ethoxycarbonylphenyl)imino-5-(4-ethoxy-
phenyl)-3H-furan-2-one (IV). a. A solution of 3.83 g
(0.01 mol) of acid IIn in 8 ml of acetic anhydride was
heated for 1 h at 70°C. The precipitate separated on
cooling was filtered off, washed with anhydrous ether,
and recrystallized from anhydrous toluene . Yield 1.5 g
(41%).
b. Acid IIn (3.83 g, 0.01 mol) was heated for 10 min
at 140°C. The residue was recrystallized. Yield 2.19 g
(60%), orange crystals, mp 149.5–151°C (toluene). IR
spectrum, ν, cm–1: 1813 (COlact), 1709 (COOEt). 1H NMR
spectrum, δ, ppm: 1.37 m (6H, CH3CH2OCO,
CH3CH2O), 4.05 q (2H, CH3CH2OCO), 4.35 q (2H,
CH3CH2), 6.23 s (1H, CH), 7.48 m (8H, 2C6H4). Found,
%: C 69.08; H 5.25; N 3.81. C21H19NO5. Calculated, %:
C 69.03; H 5.24; N 3.83.
5,5-Dimethyl-2-(2-methyl-5-nitrophenylamino)-
4-oxohex-2-enoic acid (IIIi). Yield 1.81 g (59%),
yellow crystals, mp 180–181°C (benzene–hexane). IR
spectrum, ν, cm–1: 3235(NH), 1700 (COOH). 1H NMR
spectrum, δ, ppm form A (28%): 1.10 s (9H, CMe3),
2.32 s (3H, CH3), 7.33 s (1H, CH), 7.40–7.72 m (3H,
C6H3), 11.27 s (1H, NH); form B (72%): 0.93 s (9H,
CMe3), 2.29 s (3H, CH3), 5.97 s (1H, CH), 7.40–7.72 m
(3H, C6H3). Mass spectrum, m/z (Irel, %): 306 (3.0) [M]+,
249 (22.0) [M – CMe3]+, 221 (5) [M –Me3CCO]+, 203
(100) [M – H2O – Me3CCO]+, 175 (12) [M – H2O –
Me3CCO – CO]+, 57 (81) [Me3C]+. Found, %: C 58.76;
H 5.98; N 9.09. C15H18N2O5. Calculated, %: C 58.82;
H 5.92; N 9.15. M 306.32
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
08-03-00488).
REFERENCES
5,5-Dimethyl-4-oxo-2-(4-ethoxycarbonyl-
phenylamino)hex-2-enoic acid (IIIj). Yield 2.42 g
(76%), yellow crystals, mp 161–162°C (i-PrOH). IR
spectrum, ν, cm–1: 3198, 3327 (NH), 1661, 1684, 1726
1. Shipilovskikh, S.A., Rubtsov,A.E., and Zalesov, V.V., Khim.
Geterotsikl. Soedin., 2009.
2. Rubtsov, A.E. and Zalesov, V.V., Zh. Org. Khim., 2003,
vol. 39, p. 918.
1
(COOH, COOEt). H NMR spectrum, δ, ppm, form A
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

IGIDOV et al.
3. Bukanova, E.V., Cand. Sci. (Chem.) Dissertation, Perm,
7. Belyaev, A.O., Cand. Sci. (Chem.) Dissertation, Perm,
704
2004.
2004.
4. Koz’minykh, V.O., Belyaev, A.O., Koz’minykh, E.N.,
Makhmudov, R.R., and Odegova, T.F., Khim.-Farm. Zh.,
2004, vol. 38, no. 8, p. 25.
8. Koz’minykh, V.O., Bukanova, E.V., Belyaev, A.O., and
Koz’minykh, E.N., Khim. Geterotsikl. Soedin., 2003,
p. 1427.
9. Gein, V.L., Kon’shina, L.O., andAndreichikov, Yu.S., Zh.
Org. Khim., 1992, vol. 28, p. 2134.
5. Koz’minykh, V.O. and Koz’minykh, E.N., Khim.-Farm. Zh.,
2004, vol. 38, no. 2, p. 10.
10. Koz’minykh, E.N., Belyaev, A.O., Koz’minykh, V.O.,
Makhmudov, R. R., and Odegova, T.F., Khim.-Farm. Zh.,
2002, vol. 36, no. 11, p. 28.
6. Koz’minykh, V.O., Belyaev, A.O., Koz’minykh, E.N.,
Odegova, T.F., and Makhmudov, R.R., Khim.-Farm. Zh.,
2004, vol. 38, no. 11, p. 19.
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