Acylpyruvic acid amides and hydrazides: XII. Reaction of 4-Aryl-2-hydroxy-4-oxo-2-butenic acids arylamides with triphenylphosphoranylideneacetic acid esters

Article abstract of DOI:10.1134/S1070363206070061

4-Aryl-2-hydroxy-4-oxo-2-butenic (aroylpyruvic) acid arylamides react with triphenylphosphoranylidenacetic acid esters to form products of Wittig reaction at α-carbonyl group, the 5-aryl-3-arylaminocar-bonyl-5-oxo-3-pentenoic acid esters. Features in stru

Full text of DOI:10.1134/S1070363206070061

ISSN 1070-3632, Russian Journal of General Chemistry, 2006, Vol. 76, No. 7, pp. 1041 1047.
Pleiades Publishing, Inc., 2006.
Original Russian Text
pp. 1088 1094.
V.O. Koz’minykh, V.I. Goncharov, E.N. Koz’minykh, 2006, published in Zhurnal Obshchei Khimii, 2006, Vol. 76, No. 7,
Acylpyruvic Acid Amides and Hydrazides:
XII.1 Reaction of 4-Aryl-2-hydroxy-4-oxo-2-butenic Acids
Arylamides with Triphenylphosphoranylideneacetic Acid Esters
V. O. Koz’minykha, V. I. Goncharovb, and E. N. Koz’minykha
a Perm State Pedagogical University,
ul. Sibirskaya 24, Perm 614990, Russia
e-mail: kvoncstu@yahoo.com
b Stavropol’ State Medical Academy, Stavropol’, Russia
Received December 30, 2005
Abstract 4-Aryl-2-hydroxy-4-oxo-2-butenic (aroylpyruvic) acid arylamides react with triphenylphosphor-
anylidenacetic acid esters to form products of Wittig reaction at -carbonyl group, the 5-aryl-3-arylaminocar-
bonyl-5-oxo-3-pentenoic acid esters. Features in structure of the obtained compounds are discussed.
DOI: 10.1134/S1070363206070061
The Wittig reaction of aliphatic, alicyclic and
aromatic -dicarbonyl compounds (including -keto-
esters) with methylenephosphoranes leads to forma-
tion of the products of mono- and bis-olefination,
depending on the reagent ratio and reactivity [2 8].
In the reaction of 2-hydroxy-4-oxo-4-phenyl-2-
butenic acid phenylamide (Ig) with methyl triphenyl-
phosphoraylideneacetate we isolated methyl 5-oxo-5-
phenyl-3-phenylaminocarbonyl-3(Z)-pentenoate
ad-
duct with triphenylphosphine oxide (III) of 1:1 com-
position (Scheme 1). We failed to separate com-
ponents of the complex III by ordinary methods.
Formation of such adduct is not unexpected: the stable
complexes of triphenylphosphine oxide with carbonyl
compound are well known (e.g., see [18]).
Among -dicarbonyl compound, were studied re-
actions of acetoacetic and benzoylacetic esters with
acetyl- and benzoylmethylenetriphenylphosphoranes,
and were isolated the products of C-acylation of the
latter compounds with successive heterocyclization,
2,6-disubstituted 4H-pyran-4-ones and 4-acylmethyl-
ene-4H-pyrans [9, 10]. Features in the selective ole-
fination of the carbonyl group in five- and six-
membered dioxo heterocycles with phosphoric ylides
and competitive acylation of the ylides has been con-
sidered in [7, 11 16]. Reactions of acyclic polycar-
bonyl systems containing - and -dicarbonyl frag-
ments simultaneously, including acylpyruvic acids
and related esters or amides were not studied before
our investigations.
Compounds IIa IIf and III obtained in preparative
yields are yellowish crystalline substances insoluble
in water and hexane, poorly soluble in diethyl ether
and soluble in most other ordinary organic solvemts
including ethanol, acetone, acetonitrile and chloroform.
Structure of the synthesized compounds IIa IIf and
adduct III is confirmed by the methods of UF, IR and
1H NMR spectroscopy and by mass spectrometry. IR
spectra of compounds IIa IIf include the bands of
stretching vibration at relatively high frequency 1744
1
1753 cm related to carbonyl group in the esters. Its
We established that 4-aryl-2-hydroxy-4-oxo-2(Z)-
butenic (aroylpyruvic) acid arylamides (Ia If) [their
solutions contain both enol A and -diketonate tauto-
meric forms C] readily react with triphenylphosphor-
aylideneacetic acid esters forming Wittig’s olefination
products at -carbonyl group, the 5-aryl-3-arylamino-
carbonyl-5-oxo-3(Z)-pentenoic acid esters (IIa IIf)
(for preliminary publication see [18]) and triphenyl-
phosphine oxide (Scheme 1).
position points to the absence of unsaturated group at
C2 [19] of the assumed intermediate C in the Wittig
reaction (Scheme 1). Note for comparison that in the
spectra of unsaturated 1,4-dicarboxylic acid ester aryl-
amides IV (Scheme 2) comprising the considered
functional part of structure C the ester carbonyl fre-
1
quency is no over than 1710 cm [20]. Occurrence in
the IR spectra of compounds IIa IIf of the strong
bands at 3338 3390 and 1672 1692 cm 1 NH and CO
of amide carbonyl stretching vibrations also well
conforms to their structure.
1
For communication XI, see [1].
1041

1042
KOZ’MINYKH et al.
Scheme 1.
R2
R1
O
N
O
H
O
H
A
R1
R2
O
N
H
O
O
B
Ia If
R2
R1
R2
O
R2
O
O
(C6H5)3P=CH C
(C6H5)3P=O
O
OAlk
NH
O
NH
O
O
OAlk
OAlk
C
IIa IIf
O
O
(C6H5)3P=CH C
O
OAlk
(C6H5)3P=O
Ig
(R1 = R2 = H; Alk = CH3)
NH
O
OCH3
III
Alk = CH3; R1 = H, R2 = CH3 (Ia, IIa), CH3O (Ib, IIb); R1 = CH3, R2 = CH3O (Ic, IIc), Br (Id, IId); R1 = Cl, R2 =
CH3O (Ie, IIe); R1 = R2 = H (Ig); Alk = C2H5; R1 = Br, R2 = CH3 (If, IIf).
UV spectra of compounds IIa IIf and III contain
Note for comparison that in the UV spectra of
amides I the long-wave maximum occurs at higher
bands
225 232 nm (log 4.17 4.32) and 313
331 nmm(alxog 3.34 3.66). Position of the long-wave
band is close to the maximum absorption of benzoyl-
wavelength,
340 345 nm (log 4.40) [22], than
that of compomuanxds II, due to somewhat longer cheo-
mophore system of 2(Z)-enol form (A) of the parent
amides I due to intermolecular H-bond of C2 OH
O=C4 type in the six-membered OH-chelate ring of
the -dicarbonyl group in A structure [22].
acrylic phenylamide V
310 nm [21], which has
chromophore system relamteadx to that of compounds II
(Scheme 2). The isomeric to II compounds with struc-
ture C would contain shorter chromophore system. In
the spectra of taken for comparison arylamides IV
with double bond fixed in -position the long-wave
1
The H NMR spectra of compounds IIa IIf and III
maximum exerts hypsochromic shift (
295 nm or
besides the common signals of alkoxy groups of the
ester moiety, protons 2 of two benzene rings and
lower) [20] as compared to the -unsatumraatxed esters II.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

ACYLPYRUVIC ACID AMIDES AND HYDRAZIDES: XII.
1043
Scheme 2.
O
H
Ar
O
O
NH
O
Ar
Ar
H
O
NH
NH
O
O
H
OAlk
H
IV
V
Z-I
Ar
H
O
O
O
Ar
Ar
Ar
H
O
NH
Ar
O
H
NH
O
Ar
O
O
NH
OAlk
OH
E-I
OAlk
Z-II
E-II
+
M
Ar2NH( H) CO
R1
+
M
Ar2NH( H)
R2
O
O
+
Ar1
NH
O
+
Ar2
+
Ar1CO
+
M
AlkO( H)
OAlk
+
M
AlkO CO
II
R2
R1
R1
R2
O
O
NH
OH
NH
AlkO
AlkO
O
O
O
VI
VII
(1)
(2)
CH3O
NH2;
O
O
(C6H5)3P=CH C
(C6H5)3P=O
OCH3
O
IIe, 57%
O
Cl
VIII
Alk = CH3, C2H5; R1 = H, CH3, Br, Cl; R2 = H, CH3, CH3O, Br.
amide group NH, occurs the singlets of two protons in
the C2H2 group ( 3.25 3.54 ppm) and C4H methyne
5.20 ppm (in deuterochloroform), 6.31 6.88 ppm (in
acetone-d6) and 6.92, 6.94 ppm (in DMSO-d6: two
compounds as an example). In polar media the signal
proton in aroylmethylene fragment at
4.77
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1044
KOZ’MINYKH et al.
Comparison of experimental and calculated values of chemical shift of methyne protons E(Z) in 1H NMR spectra ( , ppm)
H
of compounds I and II
calc
H
exp
H
calc
H
= |
|
H
Comp.
no.
exp
H
Solvent
Z isomer
E isomer
Z isomer
E isomer
Ia If
I
IIa IIf
IIa IIf
CDCl3
DMSO-d6
CDCl3
6.82 7.10
6.75 7.20
4.77 5.20
6.31 6.51
0.74 1.02
0.43 1.12
1.41 1.84
0.10 0.30
1.16 1.44
0.85 1.54
2.07 2.50
0.76 0.96
6.08b
6.61
5.66
7.27
a
Acetone-d6
a
b
Published data [24].
Calculation without consideration of intramolecular H-bond in OH-chelate ring.
of methyne proton is shifted downfield by 1.6 ppm
(in deuteroacetone) and 1.9 ppm (in DMSO-d6). The
shift is probably induced by solvating polarization of
carbonyl group in the C5(=O) C4H fragment, as we
also noted earlier for the related structures with the
double bond activated by carbonyl acceptors [15, 23].
mers is 0.10 0.30 ppm (in acetone-d6) and 1.41
1.84 ppm (in deuterochloroform), while for E iso-
mers respectively 0.76 0.96 and 2.07 2.50 ppm.
Thus, the calculation attests in favor of Z configura-
tion of esters II. As to the objects of comparison I
(see table), calculation also leads to conclusion of pre-
ference of the Z isomers, in conformity with the estab-
lished earlier for the amides I [22, 24]. These data
confirm also reliability of such a calculation for struc-
tural analysis of organic compounds (see [14, 15]).
In the solutions of parent aroylpyruvic amides I
predominates enol structure A: 4-aryl-2-hydroxy-4-
oxo-2(Z)-butenic acid arylamide, while -diketone
tautomer B is a minor component [24] (Scheme 1).
The enol form 2Z-A is stabilized by intramolecular
H-bond of OH-chelate type [22], E-isomer in the case
of amides I was not detected. For elucidation of steric
position of the substituents at the ethylene fragment
C3=C4H in the target compounds IIa IIf in com-
parison with the known orientation of substituents at
the unsaturated fragment C2=C3H of the parent
amides Ia Ig (Scheme 2) we calculated expected
Mass spectra of compounds II show characteristic
peaks of fragmental ions corresponding to the prin-
cipal directions of fragmentation under electron
impact (Scheme 2). Presence in the spectra of esters
II of the strong peaks corresponding to aroyl ions
(4-R1C6H4 C=O) allow to reject alternative structures
VI and VII and their geometric isomers for these
compounds and confirms proceeding of the Wittig re-
action at the carbonyl group C2=O of the aroylpyruvic
acids I.
1
chemical shift of the methine proton in the H NMR
spectra of these compounds by additive scheme taking
shielding parameters of substituents at their different
orientation near H protin [19].
Noteworthy that compounds II give strong red
color with 10% solution of NaOH in alcohol and their
solutions in trifluoroacetic acid are red-brown in color.
These tests allow to perform qualitative detection of
compounds I and monitoring their reactions.
For amides I:
E(Z)
H
0
E(Z)
E(Z)
gem
=
+
+
+
,
COAr
C=C
OH
CONHAr
For esters II:
Reaction of aroylpyruvic arylamides I with tri-
phenylphosphoraylideneacetic esters proceeds in cor-
respondence with the mechanism of Wittig reaction
[7, 25] with substitution of oxygen atom in the a
-ketogroup of the diketon form B of arylamides by
alcoxycarbonylmethylene fragment leading to forma-
tion of compounds II via isomeric intermediate C
with C2 C3 migration of double bond. The fact of
proceeding of the competitive olefination reaction at
the -ketone carbonyl confirms the data on higher
electrophilicity of the carbon aton in -ketogroup than
in the -carbonyl group of the parent amides I [22, 24].
E(Z)
H
0
E(Z)
E(Z)
CH COOAlk
gem
=
+
+
+
.
COAr
C=C
OH
E(Z)
Here
is calculated chemical shift of methyne H
protonHin E and Z isomers of compounds I and II,
0
C=C
is chemical shift of methyne H in CH= group of
E(Z)
OH
ethylene taken as origin (5.28 ppm [19]);
,
E(Z)
E(Z)
gem
,
CONHAr , and
are shielding
pCarHamCOeOteArlsk of substituents in olefiCnOsA(rtabulated values).
Comparison of experimental and calculated values
E(Z)
of methine proton chemical shifts
(see table)
shows that these parameters match bettHer to Z isomers
As is known, the synthesis of the parent aroylpy-
ruvic amides I is conducted under mild conditions
exp
H
of compounds II:
= |
calc| for the Z iso-
H
H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

ACYLPYRUVIC ACID AMIDES AND HYDRAZIDES: XII.
1045
with quantitative yield at the reaction of available
5-arylfuran-2,3-diones with aromatic amines [22, 24].
In the three-component reaction of 5-(4-chlorophenyl)-
furan-2,3-dione (VIII) with p-anisidine and methyl
triphenylphosphoraylideneacetate without isolation of
intermediately formed amide Ie we prepared methyl
3-(4-methoxyphenyl)aminocarbonyl-5-oxo-5-(4-chlo-
rophenyl)-3(Z)-pentenoate (IIe) in 57% yield and tri-
phenylphosphine oxide (Scheme 2). Thus, compounds
II can be readily obtained by Wittig reaction from
aroylpyruvic amides and directly from furan-2,3-di-
ones as well.
5-oxo-5-phenyl-3-phenylaminocarbonyl-3(Z)-
pentenoate with triphenylphosphine oxide (III)
(general procedure). a. A mixture of equimolar
amounts (5 mmol each) of corresponding aroylpyruvic
arylamides Ia Ig and esters of triphenylphosphorayl-
ideneacetic acid was heated with stirring in 50 70 ml
of ethyl acetate to complete dissolving and then re-
fluxed for 0.5 1 h. Solvent was then evaporated and
residue was grinded with ether and recrystallized from
ethanol or acetonitrile. Compounds IIa IIf and III
were obtained. From the residue after isolation of a
compound II was isolated triphenylphosphine oxide,
yields 52 74%, mp 156 157 C (from tetrachloro-
methane).
Compounds IIa IIf possess marked antimicrobial
activity to reference strains of Staphylococcus aureus
P-209 and Escherichia coli M17 [17].
Methyl 3-(4-methylphenyl)aminocarbonyl-5-
oxo-5-phenyl-3(Z)-pentenoate (IIa). Yield 1.50 g
(89%), mp 127 128 C (from ethanol). IR spectrum, ,
In attempted reaction of free aroylpyruvic acids or
methyl esters with acylmethylenetriphenylphospho-
ranes we failed to isolate individual compounds due
to strong tarring.
1
cm : 3340 (CONH amide), 1748 (C1=O ester), 1675
1683 (CONH amide, C6H5COCH=). UV spectrum,
1
(log ), nm: 225 (4.26), 331 (3.66). H NMR
max
spectra, acetone-d6, , ppm: 2.12 s (3H, CH3), 3.30 s
(2H, C2H2), 3.59 s (3H, OCH3 in COOCH3), 6.51 s
(1H, C4H), 7.00 7.65 m (9H, C6H5, C6H4), 7.44 s
(1H, NH). Found, %: C 71.47; H 5.42; N 3.90.
C20H19NO4. M 337.37. Calculated, %: C 71.20; H
5.68; N 4.15.
EXPERIMENTAL
IR spectra of esters II and adduct III were recorded
on UR-20 and Specord M-80 spectrometers from the
pasts with Vaseline oil. UV spectra of compounds II
and III were recorded on a Specord UV-Vis spectro-
photometer from solutions in ethanol 10 10 M.
1H NMR spectra of compounds II and III and of the
reference substances I were registered on RYa-2310
(60 MHz) and Bruker DRX-500 (500 MHz) instru-
ments with the solvents deuterochloroform, acetone-d6
and DMSO-d6, and internal references HMDS or
TMS. Mass spectra of compounds II were taken on a
Varian MAT-311 instrument with direct inlet mode
(electron impact), emission current 1000 mA, ionizing
voltage 70 eV, evaporator temperature 120 150°C.
4
5
Methyl 3-(4-methoxyphenyl)aminocarbonyl-5-
oxo-5-phenyl-3(Z)-pentenoate (IIb). Yield 1.50 g
(85%), mp 151 152 C (from ethanol). IR spectrum, ,
1
cm : 3390 (CONH amide), 1745 (C1=O ester), 1692
1680 (CONH amide, C6H5COCH=). UV spectrum,
1
(log ), nm: 230 (4.32), 327 (3.58). H NMR
max
spectrum, CDCl3, , ppm: 3.54 s (2H, C2H2), 3.65 s
(3H, CH3O in 4-CH3OC6H4), 3.69 s (3H, OCH3 in
COOCH3), 4.88 s (1H, C4H), 6.52 7.40 m (9H, C6H5,
C6H4), 7.24 s (1H, NH). Found, %: C 67.77; H 5.60;
N 3.84. C20H19NO5. M 353.37. Calculated, %: C
67.98; H 5.42; N 3.96.
TLC on Silufol UV-254 was used for monitoring
reactions and confirming individuality of the products
obtained, the system was benzene diethyl ether ace-
tone 10:9:1, development with iodine vapor.
Methyl 3-(4-methoxyphenyl)aminocarbonyl-5-
oxo-5-(4-methylphenyl)-3(Z)-pentenoate (IIc). Yield
1.40 g (76%), mp 143 144 C (from ethanol). IR spec-
Parent aroylpyruvic amides I were prepared from
5-arylfuran-2,3-diones by ring cleavage at the action
of arylamines [22, 24, 26, 27]. Below are given earlier
1
trum, , cm : 3355 (CONH amide), 1748 (C1=O
ester), 1675 1685 (CONH amide, 4-CH3C6H4
1
COCH=). UV spectrum,
(log ), nm: 227 (4.25),
not published data on the H NMR spectra of com-
max
1
320 (3.45). H NMR spectra, CDCl3, , ppm: 2.22 s
(3H, CH3), 3.32 s (2H, C2H2), 3.62 s (3H, CH3O in
4-CH3OC6H4), 3.67 s (3H, OCH3 in COOCH3), 5.20 s
(1H, C4H), 6.62 7.40 m (8H, 2C6H4), 7.18 s (1H,
pounds Ia, If, and Ig. 5-(4-Chlorophenyl)furan-2,3-
dione (VIII) was prepared by dehydration of 2-hyd-
roxy-4-oxo-4-(4-chlorophenyl)-2(Z)-butenic acid at
the action of acetic anhydride [28]. Triphenylphos-
phoraylideneacetic acid esters were synthesized
alongside the published method [29].
NH). Mass spectrum, m/z (Irel, %), the ions with Irel
5% are listed: 245 (6) [M 4-CH3OC6H4NH]+, 244
(37) [M 4-CH3OC6H4NH
H]+, 217 (7) [M
4-CH3OC6H4NH 4-CH3O
CO]+, 216 (40) [M
C6H4NH CO H]+ or [4-CH3C6H4CO CH=C=CH
>
Esters of 5-aryl-3-arylaminocarbonyl-5-oxo-
3(Z)-pentenoic acid (IIa IIf) and adduct of methyl
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

1046
KOZ’MINYKH et al.
COOCH3]+, 213 (10) [M 4-CH3OC6H4NH OCH3
H]+ or [4-CH3C6H4CO CH=C(C O) CH=C=O]+,
186 (8) [C12H10O2]+, 185 (12) [M 4-CH3OC6H4NH
CO OCH3 H]+ or [C12H9O2]+, 157 (7) [C11H9O]+,
129 (7), 124 (7), 123 (77) [4-CH3OC6H4NH2]+, 119
(36) [4-CH3C6H4C O]+, 109 (8), 108 (100) [4-CH3
OC6H5]+, 91 (22) [4-CH3C6H4]+, 80 (31), 65 (14), 63
(5), 53 (12), 52 (8). Found, %: C 61.47; H 4.30; N
9.23. C16H14N2O5. M 314.29. Calculated, %: C 61.14;
H 4.49; N 8.91. Found, %: C 68.87; H 5.64; N 3.96.
C21H21NO5. M 367.39. Calculated, %: C 68.65; H
5.76; N 3.81.
Ethyl 5-(4-bromophenyl)-3-(4-methylphenyl)-
aminocarbonyl-5-oxo-3(Z)-pentenoate (IIf). Yield
1.65 g (77%), mp 147 148 C (from ethanol). IR spec-
1
trum, , cm : 3338 (CONH amide), 1747 (C1=O
ester), 1677 1685 (CONH amide, 4-BrC6H4COCH=).
UV spectrum, max (log ), nm: 228 (4.28), 331 (3.34).
1H NMR spectra, acetone-d6, , ppm: 1.21 t (3H, CH3
in COOC2H5, J 7.2 Hz), 2.17 s (3H, CH3 in
4-CH3C6H4), 3.36 s (2H, C2H2), 4.13 q (3H, CH2 in
COOC2H5, J 7.0 Hz), 6.31 s (1H, C4H), 6.88 7.45 m
1
(8H, 2C6H4), 7.40 s (1H, NH). H NMR spectrum,
DMSO-d6, , ppm: 1.19 t (3H, CH3 in COOC2H5,
J 7.2 Hz), 2.17 s (3H, CH3 in 4-CH3C6H4), 3.42 s
(2H, C2H2), 4.11 q (3H, CH2 in COOC2H5, J 7.0 Hz),
6.92 s (1H, C4H), 7.02 7.58 m (8H, 2C6H4), 7.42 s
(1H, NH). Found, %: C 58.49; H 4.84; Br 18.49; N
3.39. C21H20BrNO4. M 430.29. Calculated, %: C
58.62; H 4.68; Br 18.57; N 3.26. Mass spectrum, m/z
(Irel, %), the ions with Irel > 4% (besides molecular
ions) are listed: 431 (0.5) [M (81Br isotope)]+, 429
(0.6) [M (79Br isotope)]+; 385 (5), 383 (4) [M
Methyl 3-(4-bromophenyl)aminocarbonyl-5-(4-
methylphenyl)-5-oxo-3(Z)-pentenoate (IId). Yield
1.45 g (70%), mp 157 158 C (from ethanol). IR spec-
1
trum, , cm : 3338 (CONH amide), 1753 (C1=O
ester), 1680 1690 (CONHamide, 4-CH3C6H4COCH=).
UV spectrum, max (log ), nm: 226 (4.17), 313 (3.56).
1H NMR spectrum, acetone-d6, , ppm: 2.24 s (3H,
CH3), 3.41 s (2H, C2H2), 3.68 s (3H, OCH3 in
COOCH3), 6.38 s (1H, C4H), 6.90 7.76 m (8H,
OC2H5 H]+; 357 (6), 355 (6) [M OC2H5
H
1
CO]+; 341 (7), 339 (7); 340 (5), 338 (4) [M 4-CH3
C6H4]+; 325 (17), 323 (17) [M 4-CH3C6H4NH]+;
322 (9); 296 (10), 294 (10) [M 4-CH3C6H4NH
CO H]+ or [4-BrC6H4CO CH=C=CH COOC2H5]+;
279 (21), 277 (21) [M 4-CH3C6H4NH OC2H5
H]+ or [4-BrC6H4CO CH=C(C=O) CH=C=O]+; 268
(7), 266 (7); 252 (10), 250 (10) or [C11H7BrO2]+; 251
(9), 249 (8) [M 4-CH3C6H4NH CO OC2H5 H]+
or [C11H6BrO2]+; 200 (5); 186 (7), 184 (7); 185 (89),
183 (90) [4-BrC6H4-C O]+; 172 (8); 157 (29), 155
(30) [4-BrC6H4]+; 144 (15); 133 (4) [4-CH3C6H4
N=C=O]+; 132 (5); 128 (5); 126 (7); 116 (5); 115
(10); 114 (5); 107 (100) [4-CH3C6H4NH2]+; 106 (82)
[4-CH3C6H4NH]+; 105 (5); 104 (12); 91 (18)
[4-CH3C6H4]+; 83 (5); 79 (11); 78 (8); 77 (22) [C6H5]+;
76 (23); 75 (17); 74 (5); 73 (5); 71 (6), 69 (6); 67 (9);
65 (10); 63 (6); 60 (4), 57 (10); 55 (9); 53 (6); 52 (6);
51 (9); 50 (12); 46 (5); 45 (16); 44 (6); 43 (10). Found,
%: C 61.47; H 4.30; N 9.23. C16H14N2O5. M 314.29.
Calculated, %: C 61.14; H 4.49; N 8.91.
2C6H4), 7.40 s (1H, NH). H NMR spectrum, DMSO-
d6, , ppm: 2.18 s (3H, CH3), 3.41 s (2H, C2H2),
3.62 s (3H, OCH3 in COOCH3), 6.94 s (1H, C4H),
7.16 7.63 m (8H, 2C6H4), 7.42 s (1H, NH). Found,
%: C 57.54; H 4.52; Br 19.12; N 3.17. C20H18BrNO4.
M 416.27. Calculated, %: C 57.71; H 4.36; Br 19.20;
N 3.36.
Methyl 3-(4-methoxyphenyl)aminocarbonyl-5-
oxo-5-(4-chlorophenyl)-3(Z)-pentenoate (IIe). b. A
mixture of 1.04 g (5 mmol) of 5-(4-chlorophenyl)-
furan-2,3-dione (VIII) and 0.62 g (5 mmol) of
p-anisidine was heated for 3 5 min with stirring in
50 ml of benzene, then was added 1.67 g (5 mmol) of
methyl triphenylphosphoraylideneacetate, heating with
stirring was continued till dissolving, then the mixture
was refluxed for 0.5 h. Solvent was evaporated and
residue was carefully grinded with hexane and ether
and recrystallized from ethanol and then from aceto-
nitrile. From the residual solution was isolated tri-
phenylphosphine oxide, yield 0.86 g (62%), mp 156
157 C (from tetrachloromethane). Compound IIe:
method a, yield 1.61 g (83%); method b, yield 1.10 g
(57%), mp 166 167 C (from acetonitrile). IR spec-
Adduct (1:1) of methyl 5-oxo-5-phenyl-3-phe-
nylaminocarbonyl-3(Z)-pentenoate with triphenyl-
phosphine oxide (III). Yield 2.35 g (78%), mp 105
1
1
trum, , cm : 3350 (CONH amide), 1744 (C1=O
106 C (from ethanol). IR spectrum, , cm : 3210
ester), 1672 1683 (CONH amide, 4-ClC6H4COCH=).
1H NMR spectrum, CDCl3, , ppm: 3.35 s (2H, C2H2),
3.71 s (3H, CH3O in 4-CH3OC6H4), 3.75 s (3H,
OCH3 in COOCH3), 4.77 s (1H, C4H), 6.65 7.35 m
(8H, 2C6H4), 7.24 s (1H, NH). Found, %: C 61.85; H
4.51; Cl 9.19; N 3.84. C20H18ClNO5. M 387.81. Cal-
culated, %: C 61.94; H 4.68; Cl 9.14; N 3.61.
(CONH amide), 1746 (C1=O ester), 1675 1692
1
(CONH amide, C6H5COCH=). H NMR spectrum,
acetone-d6, , ppm: 3.25 s (2H, C2H2), 3.52 s (3H,
OCH3 in COOCH3), 6.88 s (1H, C4H), 7.15 7.95 m
(26H, 5C6H5, NH). Found, %: C 73.65; H 5.49; N
2.18. C37H32NO5P. M 601.63. Calculated, %: C
73.87; H 5.36; N 2.33.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006

ACYLPYRUVIC ACID AMIDES AND HYDRAZIDES: XII.
1047
2-Hydroxy-4-oxo-4-phenyl-2(Z)-butenic
(4-methylphenyl)amide (Ia). mp 132 133 C (from
toluene). Published: mp 123 124 C [22]. H NMR
14. Koz’minykh, E.N., Berezina, E.S., and Koz’mi-
nykh, V.O., Zh. Obshch. Khim., 1996, vol. 66, no. 7,
p. 1128.
1
spectra, CDCl3, , ppm: 2.26 s (3H, CH3), 4.55 s (2H,
C3H2, -diketone form B, 1.5%), 7.10 s (1H, C3H,
enol form A, 98.5%), 7.20 8.03 m (9H, C6H5, C6H4),
9.02 br.s (1H, NH), 14.58 br.s (1H, OH).
15. Koz’minykh, E.N., Doctorate (Pharmacy) Disserta-
tion, Perm, 1999.
16. Koz’minykh, V.O., Lomidze, K.Sh., and Koz’mi-
nykh, E.N., and Berezin, A.N., Khim. Geterotsikl.
Soed., 2004, no. 4, p. 619.
4-(4-Bromophenyl)-2-hydroxy-4-oxo-2(Z)-bute-
nic (4-methylphenyl)amide (If). mp 154 155 C
17. Koz’minykh, E.N., Igidov, N.M., Voronina, E.V., and
Koz’minykh, V.O., Nauchnye Trudy NII Farmatsii
(Proceedings of Research Pharmaceutical Institute),
Supply), Moscow: Znaniye, 1997, vol. 37, part II,
p. 19.
1
(from toluene) [26]. H NMR spectrum, DMSO-d6, ,
ppm: 2.28 s (3H, CH3), 4.62 s (2H, C3H2, form B,
7.2%), 7.13 s (1H, C3H, form A, 92.8%), 7.25 8.12 m
(8H, 2C6H4), 10.58 br.s (1H, NH).
18. Hercouet, A. and Le Corre, M., Tetrahedron, 1981,
2-Hydroxy-4-oxo-4-phenyl-2(Z)-butenic phe-
nylamide (Ig). mp 114 115 C (from ethanol). Pub-
vol. 37, no. 16, p. 2867.
1
19. Ioffe, B.V., Kostikov, R.R., and Razin, V.V., Fizi-
cheskie metody opredeleniya structury organicheskikh
soedinenii (Physical Methods for Determination Stru-
cture of Organic Compounds), Moscow: Vysshaya
Skola, 1984.
lished: mp 113 114 C [22], 124 125 C [26, 27]. H
NMR spectrum, DMSO-d6, , ppm: 4.60 s (2H, C3H2,
form B, 9.7%), 7.12 s (1H, C3H, form A, 90.3%),
7.15 8.07 m (10H, 2C6H5), 10.37 br.s (1H, NH).
20. Mehta, N.B., Phillips, A.P., Lui, F.F., and
Brooks, R.E., J. Org. Chem., 1960, vol. 25, no. 6,
p. 1012.
REFERENCES
1. Koz’minykh, V.O., Milyutin, A.V., Makhmudov, R.R.,
Belyaev, A.O., and Koz’minykh, E.N., Khim.-Pharm.
Zh., 2004, vol. 38, no. 12, p. 21.
21. Awad, W.I. and Ismail, M.F., J. Chem. UAR, 1971,
vol. 14, no. 2, p. 141.
22. Andreichikov, Yu.S., Nalimova, Yu.A., Tendryako-
va, S.P., and Vilenchik, Ya.M., Zh. Org. Khim., 1978,
vol. 14, no. 1, p. 160.
2. Parrick, J., Canad. J. Chem., 1964, vol. 42, no. 1,
p. 190.
3. Strzelecka, H., C. R., 1971, vol. 273, no. 18, p. 1194.
4. Taylor, R.J.K., Synthesis, 1977, no. 8, p. 566.
23. Andreichikov, Yu.S. and Koz’minykh, V.O., Zh. Org.
Khim., 1989, vol. 25, no. 3, p. 618.
5. Knorr, H., Ried, W., Knorr, U., Pustoslemsek, P., and
24. Belyaev, A.O., Candidate Sci. (Pharmacy) Disserta-
tion, Kursk, 2004.
Oremek, G., Lieb. Ann., 1977, no. 4, p. 545.
6. Hartke, K., Kumar, A., and Koester, J., Lieb. Ann.,
25. Barton, D.H.R. and Ollis, W.D., Comprehensive Or-
ganic Chemistry, Oxford: Pergamon, 1979, vol. 3.
Translated under the title Obshaya organicheskaya
khimiya, Moscow: Khimiya, 1983, vol. 5, p. 114.
1983, no. 2, p. 267.
7. Murphy, P.J. and Lee, S.E., J. Chem. Soc., Perkin
Trans. 1, 1999, no. 20, p. 3049.
8. Mawaziny, S. and Makky, S., Phosph., Sulfur Silicon,
and Relat. Elem., 2000, vol. 167, no. 1, p. 61.
26. Milyutin, A.V., Koz’minykh, E.N., Krylova, I.V.,
Goleneva, A.F., Makhmudov, R.R., Voronina, E.V.,
and Koz’minykh, V.O., Nauchnye Trudy NII Farma-
tsii (Proceedings of Research Pharmaceutical Insti-
tute), Moscow: Znaniye, 1997, vol. 36, part II, p. 13.
9. Strzelecka, H., C. R., 1965, vol. 260, no. 14, p. 3989.
10. Strzelecka, H., Ann. Chim., 1966, vol. 1, nos. 5 6,
p. 201.
11. Andreichikov, Yu.S., Koz’minykh, E.N., and Koz’mi-
nykh, V.O., Zh. Obshch. Khim., 1985, vol. 55, no. 7,
p. 1653.
27. Koz’minykh, E.N., Igidov, N.M., Shavkunova, G.A.,
Yakovlev, I.B., Shelenkova, S.A., Kolla, V.E., Voro-
nina, E.V., and Koz’minykh, V.O., Khim.-Pharm. Zh.,
1996, vol. 30, no. 7, p. 31.
12. Andreichikov, Yu.S., Koz’minykh, V.O., and Mane-
lova, E.N., Zh. Org. Khim., 1985, vol. 21, no. 2,
p. 402.
28. Kozminykh, V.O., Igidov, N.M., Kozminykh, E.N.,
and Aliev, Z.G., Pharmazie, 1993, pp. 48, 99.
13. Koz’minykh, E.N., Igidov, N.M., Koz’minykh, V.O.,
and Berezina, E.S., Zh. Org. Khim., 1994, vol. 30,
no. 7, p. 999.
29. Isler, O., Gutmann, H., Montavon, M., Ruegg, R.,
Ryser, G. and Zeller, P., Helv. Chim. Acta., 1957,
vol. 40, p. 1242.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 76 No. 7 2006