Alkyl 3-amino-5-aryl-2-benzoyl-5-oxo-2-pentenoates as new chelating ligands and reagents of heterocyclic synthesis

Article abstract of DOI:10.1023/B:RUCB.0000009652.31299.80

A method for the synthesis of alkyl 3-amino-5-aryl-2-benzoyl-5-oxo-2- pentenoates from Ni chelates of alkyl benzoylacetates and aroylacetonitriles was proposed. The compounds obtained were used for preparation of ethyl 4-amino-6-aryl-2-phenylnicotinates and Ni and B chelates.

Full text of DOI:10.1023/B:RUCB.0000009652.31299.80

Russian Chemical Bulletin, International Edition, Vol. 52, No. 9, pp. 2057—2062, September, 2003
2057
Alkyl 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ2ꢀpentenoates
as new chelating ligands and reagents of heterocyclic synthesis
ꢀ
V. A. Dorokhov, A. V. Vasilyev, S. V. Baranin, and A. S. Vorushilov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: vador@ioc.ac.ru
A method for the synthesis of alkyl 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ2ꢀpentenoates from
Ni chelates of alkyl benzoylacetates and aroylacetonitriles was proposed. The compounds
obtained were used for preparation of ethyl 4ꢀaminoꢀ6ꢀarylꢀ2ꢀphenylnicotinates and Ni and B
chelates.
Key words: aroylacetonitriles, diphenylboron chelates, nickel chelates, pyranꢀ2ꢀones,
pyrylium salts, pyridines.
Scheme 1
Within the scope of studies dealing with the search for
new promising reagents for organic synthesis and chelatꢀ
ing ligands, our attention was attracted by aminovinyl
carbonyl compounds of
structural type A, which
can formally be repreꢀ
sented as the products of
addition of methyleneꢀacꢀ
tive βꢀdiketones or esters
of βꢀoxocarboxylic acids
to the C≡N bond of acylꢀ
R1 = Alk, OAlk; R2, R3 = Alk, Ar
acetonitriles.
As noted previously,1—3 adducts of type A cannot be
prepared directly from nitriles and βꢀdicarbonyl comꢀ
pounds; therefore, instead of the latter reagents, we proꢀ
posed performing the reaction with their chelates. For
example, we found that the Ni chelate of ethyl acetoacꢀ
etate can add to aroylacetonitriles in boiling xylene to
give Ni complexes incorporating the corresponding comꢀ
pounds A (R1 = OEt, R2 = Me, R3 = Ar) as ligands. It was
found, however, that destruction of the chelates on treatꢀ
ment with AcOH is accompanied by partial or complete
intramolecular cyclization of the evolved free ligands to
give 3ꢀacetylꢀ4ꢀaminoꢀ6ꢀarylpyranꢀ2ꢀones.3 In this study,
we report that more stable adducts of A can be obtained
from the Ni complexes of benzoylacetates.
It was found that refluxing of a mixture of aroylꢀ
acetonitriles 1a—d and chelates 2 or 3 in benzene gives
nickel complexes 4a—d or 5a in 50—75% yields. On treatꢀ
ment with AcOH, these complexes are smoothly conꢀ
verted into free ligands, namely, 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenꢀ
zoylꢀ5ꢀoxoꢀ2ꢀpentenoates 6a—d and 7a, which exist in
solutions at 20—30 °C as mixtures of Eꢀ and Zꢀisomers in
∼1 : 1 ratio (Scheme 1).
R = Et (2, 4, 6), Bu (3, 5, 7);
Ar = Ph (a), 4ꢀMeC6H4 (b), 4ꢀClC6H4 (c), 4ꢀMeOC6H4 (d)
Compounds 6a—d and 7a display a much higher
thermal stability than their analogs obtained from the
Ni chelates of ethyl acetoaceate; they cyclize to pyraꢀ
nones only on refluxing in xylene (for more details, see
below).
Ketoesters 6a—d and 7a are white crystalline solids
readily soluble in most organic solvents. The mass spectra
of these compounds exhibit [M]+ peaks, and the H and
1
13C NMR spectra (in DMSOꢀd6 and CDCl3 at 20—30 °C)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1947—1952, September, 2003.
1066ꢀ5285/03/5209ꢀ2057 $25.00 © 2003 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 52, No. 9, September, 2003
Dorokhov et al.
are characterized by double sets of signals with almost
equal intensities. The H NMR spectrum of compound
6a in DMSOꢀd6 recorded at 70 °C exhibits one set of
broadened signals, which confirms the occurrence of an
equilibrium between isomers.
to fourꢀcoordinate boron. The 1H NMR spectra (in
DMSOꢀd6) exhibit singlets at δ 10.50—10.51 (NH) and
δ 4.77—4.80 (COCH2); hence, the alternative structures
of type B (with a different coorꢀ
1
dination of boron) can be ruled
Compounds 6 and 7 can evidently be used as chelating
ligands, which clearly follows from the method by which
they were synthesized (see Scheme 1).
out. These data also confirm inꢀ
directly the structure attributed
to chelates 4 and 5 (with a simiꢀ
Complexes 4a—d and 5a are highꢀmelting redꢀcolꢀ
ored powders poorly soluble in most organic solvents. It is
difficult to free them completely from impurities. Although
chelates 4b,c were finally obtained in an analytically pure
state, crude compounds 4 and 5 were still used to isolate
the free ligands. Apparently, the metal atom in the molꢀ
ecules of complexes 4a—d and 5a is coordinated to the O
and N atoms of the deprotonated enaminone fragment.
The data of IR spectroscopy are in line with the structures
4a—d and 5a. The IR spectra (KBr) exhibit narrow abꢀ
sorption bands at 3288—3252 cm–1 (NH) and intense
absorption in the regions of 1692—1684 (C=O) and
1590—1580 cm–1 (delocalized system of multiple bonds
in the chelate ring).
lar coordination of the Ni atom).
In addition, esters 6a—d and
7a are new, promising polyfuncꢀ
tional reagents, which can be
used in heterocyclic synthesis.
As noted above, on refluxing in xylene, ketoesters
6a—d and 7a cyclize to give aminopyranones 10a—d in
∼50% yields (Scheme 3).
Scheme 3
As a rule, boron complexes are more readily soluble in
organic solvents than nickel complexes, which facilitates
spectroscopic studies. Therefore, we prepared diphenylꢀ
boron chelates 8 and 9, which were paleꢀyellow crystalꢀ
line compounds readily soluble in most organic solvents
(Scheme 2). They are stable in air in the solid state and as
solutions in DMSO (for several weeks).
Ar = Ph (a), 4ꢀMeC6H4 (b), 4ꢀClC6H4 (c), 4ꢀMeOC6H4 (d)
Pyranones 10a—d are white crystalline solids moderꢀ
ately soluble in most organic solvents; they crystallize
from benzene, xylene, and ethanol. The mass spectra of
these compounds tend to exhibit [M]+ peaks. The IR
spectra (KBr) contain narrow absorption bands in the
region of 3385—3372 cm–1 (free NH) and broadened
bands at 3284—3230 cm–1 (bound NH). In the 1H NMR
spectrum of compound 10a, the proton signals of the
NH2 group occur as broadened singlets with δ 9.67 (bound
NH) and δ 5.63 (free NH), which points to the formation
of an N—H...O intramolecular hydrogen bond.
Scheme 2
On treatment of ketoesters 6a—c and 7a with an
ethanolic solution of HCl, previously unknown pyrylium
salts 11a—c and 12a were synthesized in high yields
(Scheme 4). These compounds are prepared even more
conveniently using Ni chelates 4a—c and 5a, i.e., interꢀ
mediates in the synthesis of compounds 6 and 7.
Salts 11a—c and 12a are colorless crystalline solids
readily soluble in DMSO, EtOH, and CHCl3 and sparꢀ
ingly soluble in most other organic solvents including
acetone and MeCN and in water. In the mass spectra
of these compounds, the peaks corresponding to the
[M – HCl]+ ion are most intense. A specific feature of
the 1H NMR spectra (in CDCl3) is the presence of broadꢀ
ened singlets with δ 12.32—12.80 and 8.87—9.17 (NH2)
and characteristic singlets with δ 8.66—8.76 (H(5)).
8: R = Et, Ar = 4ꢀClC6H4
9: R = Bu, Ar = Ph
The structure of complexes 8 and 9 was confirmed by
1
IR spectroscopy, H NMR spectroscopy, and mass specꢀ
trometry. The mass spectra of these compounds exhibit a
pattern typical of boron chelates, namely, no molecular
ion peak and the peak of the [M – Ph]+ ion as the most
intense. The 11B NMR signals at δ 4.66—5.46 correspond

Alkyl 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ2ꢀpentenoates Russ.Chem.Bull., Int.Ed., Vol. 52, No. 9, September, 2003 2059
Scheme 4
on a Bruker ACꢀ200Р instrument (64.21 MHz) with Et2O•BF3
as the internal standard. IR spectra were measured on a Specord
Mꢀ80 instrument in KBr pellets or in solutions in CHCl3. Mass
spectra (EI, 70 eV) were run on a Kratos MSꢀ30 mass spectromꢀ
eter. The elemental analysis for C, H, N, B, and Cl was perꢀ
formed in the Laboratory for Microanalysis at the N. D. Zelinsky
Institute of Organic Chemistry of the RAS. All solvents were
dehydrated. Butyl benzoylacetate was synthesized by a known
procedure.7
Nickel(2+) chelate of ethyl benzoylacetate (2) was prepared
similarly to a known method8 of the synthesis of the nickel
chelate of ethyl acetoacetate. The salt NiCl2•6H2O (12.0 g,
50 mmol) was dissolved in 80 mL of a 4 M solution of ammonia.
Ethyl benzoylacetate (19.2 g, 100 mmol) was added to the reꢀ
sulting solution and the mixture was stirred for 15 min. The
lightꢀblue precipitate that formed was filtered off, washed with
water (5×150 mL), and dried in vacuo for 4 h (100 °C, 2 Torr) to
give 15.7 g (71%) of complex 2 as a green oil readily soluble in
most organic solvents (hexane, benzene, chloroform, ethanol,
etc.) and decomposing on heating above 153 °C. No further
purification of the resulting chelate was performed. Found (%):
Ni, 12.52. C22H22NiO6. Calculated (%): Ni, 13.31. IR (KBr),
R = Et (11), Bu (12);
Ar = Ph (a), 4ꢀMeC6H4 (b), 4ꢀClC6H4 (c)
ν/cm–1: 1625, 1545, 1480, 1275, 1190. IR (CHCl3), ν/cm–1
:
1620, 1530, 1485, 1272, 1192.
Nickel(2+) chelate of butyl benzoylacetate (3). As in the synꢀ
thesis of complex 2, butyl benzoylacetate (22.0 g, 100 mmol)
was converted into chelate 3, yield 16.9 g (68%), green oil
(dec.p. >134 °C). This product was also used without further puꢀ
rification. Found (%): Ni, 11.37. C26H30NiO6. Calculated (%):
Ni, 11.81. IR (KBr), ν/cm–1: 1620, 1536, 1488, 1276, 1192.
IR (CHCl3), ν/cm–1: 1624, 1520, 1488, 1276, 1188.
Heating of compounds 6a—c with ammonium acetate
in AcOH gives 4ꢀaminoꢀ6ꢀarylꢀ2ꢀphenylpyridineꢀ3ꢀcarꢀ
boxylates 13a—c (Scheme 5).
Scheme 5
Nickel(2+) chelates of ethyl 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀ
oxoꢀ2ꢀpentenoates 4a—d, 5a (general procedure). Nitrile 1a—d
(20 mmol) was added in portions at 70 °C to a solution of
10 mmol of complex 2 or 3 in 25 mL of benzene. The reaction
mixture was refluxed for 8 h, and the red precipitates that formed
were filtered off, washed with benzene (3×15 mL) and Et2O
(3×10 mL), and dried in vacuo.
Nickel(2+) chelate of ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀmethylꢀ
phenyl)ꢀ5ꢀoxoꢀ2ꢀpentenoate (4b). Yield 75%. For the preparaꢀ
tion of an analytically pure specimen, the complex was recrysꢀ
tallized from a large amount of benzene, dec.p. >220 °C.
Found (%): C, 66.31; H, 5.30; N, 3.68; Ni, 7.36. C42H40N2NiO8.
Calculated (%): C, 66.42; H, 5.31; N, 3.69; Ni, 7.73. IR (KBr),
ν/cm–1: 3288 nar (NH), 1684, 1580, 1448, 1416.
Nickel(2+) chelate of ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀchloroꢀ
phenyl)ꢀ5ꢀoxoꢀ2ꢀpentenoate (4c). Yield 82%. For the preparaꢀ
tion of an analytically pure specimen, the complex was recrysꢀ
tallized from a large amount of benzene, dec.p. >230 °C.
Found (%): C, 60.08; H, 4.38; Cl, 8.87; N, 3.67; Ni, 7.20.
C40H34Cl2N2NiO8. Calculated (%): C, 60.03; H, 4.28; Cl, 8.86;
N, 3.50; Ni, 7.34. IR (KBr), ν/cm–1: 3252 nar (NH), 1692,
1584, 1448, 1408.
Nickel(2+) chelate of ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ5ꢀpheꢀ
nylꢀ2ꢀpentenoate (4a) (yield 65%, dec.p. >203 °C), nickel(2+)
chelate of ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀoxoꢀ
2ꢀpentenoate (4d) (yield 57%, dec.p. >195 °C), and nickel(2+)
chelate of butyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ5ꢀphenylꢀ2ꢀpentenoate
(5a) (yield 50%, dec.p. >190 °C) no further purification. IR,
chelate 4a (KBr), ν/cm–1: 3275 nar (NH), 1685, 1695, 1585,
1460, 1414. IR, chelate 4d (KBr), ν/cm–1: 3260 nar (NH),
Ar = Ph (a), 4ꢀMeC6H4 (b), 4ꢀClC6H4 (c)
The mass spectra of compounds 13 contain peaks for
the [M]+ ions, while the 1H NMR spectra (in CDCl3)
tend to exhibit singlets in the region of δ 6.87—6.93 (H(5))
and broadened signals at δ 5.67—5.71 (NH2). Only few
multistep syntheses of 4ꢀaminonicotinic acid derivatives
based on modification of picolines are known.4,5 Meanꢀ
while, derivatives of 4ꢀaminonicotinic acid are of interꢀ
est as potential biologically active substances6 and as
naphthyridine precursors.5
There is every reason for believing that the above exꢀ
amples are far from exhausting the scope of using comꢀ
pounds 6 and 7 as reagents and chelating ligands.
Experimental
1H and 13C NMR spectra were recorded on a Bruker
WMꢀ250 instrument (250.13 and 62.9 MHz, respectively) using
Me4Si as the internal standard. 11В NMR spectra were recorded

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Dorokhov et al.
1690, 1600, 1590, 1452, 1425. IR, chelate 5a (KBr), ν/cm–1
3265 nar (NH), 1688, 1605, 1588, 1445, 1409.
:
Calculated (%): C, 68.65; H, 5.76; N, 3.81. MS, m/z: 367 [M]+.
IR (KBr), ν/cm–1: 3400 nar (free NH); 3215 br (bound NH);
1680, 1600 (C=O, C=C); 1490. 1H NMR (DMSOꢀd6), δ: 10.37,
9.14, 8.65, 8.13 (all br.s, total 2 H, NH2); 8.10—6.90 (m,
total 9 H, Ph, 4ꢀMeOC6H4); 4.46, 4.24 (both s, total 2 H,
Esters of 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ2ꢀpentenoic acꢀ
ids 6a—d, 7a (general procedure). Acetic acid (3 mL) was added
to a suspension of complex 4a—d or 5a (5 mmol) in 15 mL of
CHCl3. The mixture was heated to reflux, cooled to 20 °C, and
stirred for 2 h. The organic layer was washed with water
(3×10 mL) and dried over CaCl2. The solvent was evaporated
and the residue was recrystallized from benzene or from a benꢀ
zene—hexane mixture.
4ꢀMeOC6H4COCH2); 3.86, 3.84 (both s, total
3 H,
4ꢀMeOC6H4); 3.78, 3.50 (both q, total 2 H, OCH2, J = 7.3 Hz);
0.60, 0.46 (both t, total 3 H, MeCH2, J = 7.3 Hz).
Butyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ5ꢀphenylꢀ2ꢀpentenoate (7a).
Yield 80%, m.p. 103—104 °C (benzene—hexane, 3 : 1).
Found (%): C, 72.31; H, 6.34; N, 3.83. C22H23NO4. Calcuꢀ
Ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ5ꢀphenylꢀ2ꢀpentenoate (6a).
Yield 85%, m.p. 129—130 °C (benzene—hexane, 1 : 1).
Found (%): C, 71.16; H, 5.72; N, 3.92. C20H19NO4. Calcuꢀ
lated (%): C, 71.20; H, 5.68; N, 4.15. MS, m/z: 337 [M]+. IR
(KBr), ν/cm–1: 3430 br (free NH); 3205 nar (bound NH); 1680,
1660, 1615 (C=O, C=C). 1H NMR* (DMSOꢀd6), δ: 10.32,
9.13, 8.61, 8.41 (all br.s, total 2 H, NH2); 8.15—7.20 (m, 10 H,
2 Ph); 4.46, 4.26 (both s, total 2 H, PhCOCH2); 3.78, 3.49
(both q, total 2 H, OCH2, J = 7.3 Hz); 0.60, 0.45 (both t,
total 3 H, Mе, J = 7.3 Hz). 1H NMR (70 °C, DMSOꢀd6), δ: 9.30
(br.s, 2 H, NH2); 8.20—7.20 (m, 10 H, 2 Ph); 4.50 (br.s, 2 H,
PhCOCH2); 3.75 (br.s, 2 H, OCH2); 0.75 (br.s, 3 H, Mе).
Ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀmethylphenyl)ꢀ5ꢀoxoꢀ2ꢀ
pentenoate (6b). Yield 88%, m.p. 143—144 °C (benzene—hexꢀ
ane, 3 : 1). Found (%): C, 71.56; H, 6.00; N, 3.82. C21H21NO4.
Calculated (%): C, 71.78; H, 6.02; N, 3.99. MS, m/z: 351 [M]+.
IR (KBr), ν/cm–1: 3400 nar (free NH); 3200 br (bound NH);
1688, 1596 (C=O, C=C); 1480. IR (CHCl3), ν/cm–1: 3450 br
lated (%): C, 72.04; H, 6.30; N, 3.72. MS, m/z: 365 [M]+
.
IR (KBr), ν/cm–1: 3380 nar (free NH); 3200 br (bound NH);
1690, 1580 (C=O, C=C). IR (CHCl3), ν/cm–1: 3440 br (NH2);
1690, 1605 (C=O, C=C). 1H NMR (DMSOꢀd6), δ: 10.36, 9.19,
8.64, 8.40 (all br.s, total 2 H, NH2); 8.10—7.25 (m, 10 H, 2 Ph);
4.53, 4.17 (both s, total 2 H, PhCOCH2); 3.75, 3.49 (both t,
total 2 H, OCH2, J = 6.7 Hz); 1.05—0.40 (m, 7 H, CH2CH2Me).
13C NMR (DMSOꢀd6), δ: 193.61 and 193.95 (PhCOCH2),
168.66, 168.94, 165.88, 164.84, 142.72, 143.44, 136.09, 133.35,
133.19, 130.54, 129.73, 128.73, 128.67, 127.97, 127.81, 127.69,
127.44, 126.38, 100.16, 97.94, 62.71 and 62.21 (OCH2), 44.84
and 44.25 (CH2CH2Me), 29.76 and 29.45 (CH2Me), 18.26 and
13.43 (Me).
Diphenylboron chelate of ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ
(4ꢀchlorophenyl)ꢀ5ꢀoxoꢀ2ꢀpentenoate (8). Ketoester 6c (0.37 g,
1 mmol) was dissolved in 5 mL of THF in an atmosphere of dry
nitrogen, and Ph2BOBu (0.24 g, 1 mmol) was added. The mixꢀ
ture was refluxed for 5 min and left for 18 h. The solvent was
evaporated in vacuo and the residue was twice recrystallized
from hexane to give 0.29 g (54%) of chelate 8, m.p. 137—138 °C
(hexane). Found (%): C, 71.74; H, 5.31; B, 1.72; Cl, 6.27;
N, 2.80. C23H27BClNO4. Calculated (%): C, 71.73; H, 5.08;
B, 2.02; Cl, 6.62; N, 2.61. MS, m/z: 458 [M – Ph]+. IR (KBr),
ν/cm–1: 3288 (NH); 1684 (C=O); 1616, 1416. IR (CHCl3),
1
(NH2); 1684, 1604 (C=O, C=C); 1482. H NMR (DMSOꢀd6),
δ: 10.32, 9.10, 8.57, 8.35 (all br.s, total 2 H, NH2); 7.92—7.83,
7.50—7.24 (both m, total 9 H, Ph, 4ꢀMeC6H4); 4.40, 4.20
(both s, total 2 H, 4ꢀMeC6H4COCH2); 3.73, 3.49 (both q,
total 2 H, OCH2, J = 7.3 Hz); 2.38, 2.36 (both s, total 3 H,
4ꢀMeC6H4); 0.58, 0.43 (both t, total 3 H, 2 MeCH2, J = 7.3 Hz).
1H NMR (CDCl3), δ: 9.30, 6.40 (both br.s, total 2 H, NH2);
8.05—7.20 (m, 9 H, Ph, 4ꢀMeC6H4); 4.50, 4.25 (both s, total 2 H,
PhCOCH2); 3.90, 3.75 (both q, total 2 H, OCH2, J = 7.2 Hz);
2.50, 2.40 (both s, total 3 H, 4ꢀMeC6H4); 0.75, 0.60 (both t,
total 3 H, MeCH2, J = 7.2 Hz).
Ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀchlorophenyl)ꢀ5ꢀoxoꢀ2ꢀ
pentenoate (6c). Yield 91%, m.p. 142—143 °C (benzene).
Found (%): C, 64.53; H, 5.00; Cl, 9.32; N, 3.72. C20H18ClNO4.
Calculated (%): C, 64.61; H, 4.88; Cl, 9.53; N, 3.77. MS, m/z:
371 [M]+. IR (KBr), ν/cm–1: 3405 nar (free NH); 3210 br
(bound NH); 1685, 1610 (C=O, C=C); 1480. IR (CHCl3),
ν/cm–1: 3440 br (NH2); 1688, 1593 (C=O, C=C); 1487.
1H NMR (DMSOꢀd6), δ: 10.37, 9.14, 8.55, 8.37 (all br.s,
total 2 H, NH2); 8.20—7.15 (m, total 9 H, Ph, 4ꢀClC6H4); 4.43,
4.19 (both s, total 2 H, 4ꢀClC6H4COCH2); 3.70, 3.47 (both q,
total 2 H, OCH2, J = 7.3 Hz); 0.61, 0.45 (both t, total 3 H, Mе,
J = 7.3 Hz). 1H NMR (CDCl3), δ: 9.37, 6.25 (both br.s, total 2 H,
NH2); 8.10—7.23 (m, total 9 H, Ph, 4ꢀClC6H4); 4.45, 4.17
(both s, total 2 H, PhCOCH2); 3.89, 3.73 (both q, total 2 H,
OCH2, J = 7.2 Hz); 0.75, 0.63 (both t, total 3 H, Mе, J = 7.2 Hz).
Ethyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀoxoꢀ2ꢀ
pentenoate (6d). Yield 88%, m.p. 97—98 °C (benzene—hexane,
1 : 1). Found (%): C, 68.56; H, 5.90; N, 3.62. C21H21NO5.
1
ν/cm–1: 3372 (NH); 1688 (C=O); 1608, 1580, 1480. H NMR
(DMSOꢀd6), δ: 10.51 (br.s, 1 H, NH); 8.11—6.94 (m, 19 H,
3 Ph, 4ꢀClC6H4); 4.77 (s, 2 H, 4ꢀClC6H4COCH2); 3.57 (t, 2 H,
OCH2, J = 7.3 Hz); 0.53 (t, 3 H, Mе, J = 7.3 Hz). 11B NMR
(DMSOꢀd6), δ: 5.46 (br.s).
Diphenylboron chelate of butyl 3ꢀaminoꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ5ꢀ
phenylꢀ2ꢀpentenoate (9) was prepared from ketoester 7a (0.37 g,
1 mmol) and Ph2BOBu (0.24 g, 1 mmol) as described in the
synthesis of complex 8. The yield of chelate 9 was 0.32 g (60%),
m.p. 114—115 °C (hexane). Found (%): C, 77.24; H, 6.18;
B, 1.95; N, 2.50. C34H32BNO4. Calculated (%): C, 77.13;
H, 6.09; B, 2.04; N, 2.65. MS, m/z: 452 [M – Ph]+. IR (KBr),
ν/cm–1: 3324 (NH); 1700, 1680 (C=O); 1616, 1580. IR (CHCl3),
1
ν/cm–1: 3376 (NH); 1695 (C=O); 1612, 1593, 1470. H NMR
(DMSOꢀd6), δ: 10.50 (br.s, 1 H, NH); 8.11—7.10 (m, 20 H,
4 Ph); 4.80 (s, 2 H, PhCOCH2); 3.55 (t, 2 H, OCH2, J = 6.7 Hz);
1.00—0.50 (m, 7 H, MeCH2CH2). 11B NMR (DMSOꢀd6), δ:
4.66 (br.s).
4ꢀAminoꢀ6ꢀarylꢀ3ꢀbenzoylpyranꢀ2ꢀones 10a—d (general proꢀ
cedure). A solution of ketoester 6a—d (1 mmol) (ethyl ester 6a
can be replaced by butyl ester 7a) in 25 mL of оꢀxylene was
refluxed for 8 h. The solvent was evaporated in vacuo and the
residue was successively recrystallized from benzene and ethaꢀ
nol to give the corresponding pyranones 10a—d.
* The ratio of signals of the Eꢀ and Zꢀisomers in this spectrum,
like that in the spectra of compounds 6b—d and 7a (at 20 °C), is
close to 1 : 1.
4ꢀAminoꢀ3ꢀbenzoylꢀ6ꢀphenylpyranꢀ2ꢀone (10a). Yield 45%
(with ketoester 7a, the yield was 40%), m.p. 253—254 °C

Alkyl 3ꢀaminoꢀ5ꢀarylꢀ2ꢀbenzoylꢀ5ꢀoxoꢀ2ꢀpentenoates Russ.Chem.Bull., Int.Ed., Vol. 52, No. 9, September, 2003 2061
(EtOH). Found (%): C, 73.94; H, 4.69; N, 4.88. C18H13NO3.
Calculated (%): C, 74.22; H, 4.50; N, 4.81. MS, m/z: 291 [M]+.
IR (KBr), ν/cm–1: 3372 nar (free NH); 3284 br (bound NH);
1674, 1652 (C=O); 1592. 1H NMR (DMSOꢀd6), δ: 9.14, 8.48
(both br.s, each 1 H, NH2); 7.80—7.42 (m, 10 H, 2 Ph); 6.80 (s,
1 H, H(5)). 1H NMR (CDCl3), δ: 9.67, 5.63 (both br.s, each 1 H,
NH2); 7.88—7.50 (m, 10 H, 2 Ph); 6.34 (s, 1 H, H(5)).
4ꢀAminoꢀ3ꢀbenzoylꢀ6ꢀ(4ꢀmethylphenyl)pyranꢀ2ꢀone (10b).
Yield 52%, m.p. 274—275 °C (EtOH). Found (%): C, 74.94;
H, 4.86; N, 4.58. C19H15NO3. Calculated (%): C, 74.74; H, 4.95;
N, 4.59. MS, m/z: 305 [M]+. IR (KBr), ν/cm–1: 3380 nar (free
NH); 3220 br (bound NH); 1676, 1648 (C=O); 1596, 1508.
1H NMR (DMSOꢀd6), δ: 9.15, 8.45 (both br.s, each 1 H, NH2);
7.70—7.30 (m, 9 H, Ph, 4ꢀMeC6H4); 6.71 (s, 1 H, H(5)); 2.35
(s, 3 H, Me). 13C NMR (DMSOꢀd6), δ: 196.09 (PhCO); 162.13,
161.61, 160.52, 142.17, 141.87, 130.98, 130.23, 128.37, 128.07,
126.02, 96.79, 93.49; 21.49 (Me).
3368 (NH); 3040 (NH); 1712, 1656, 1484. 1H (CDCl3), δ: 12.62,
8.87 (both br.s, each 1 H, NH2); 8.66 (s, 1 H, H(5)); 7.88, 7.30
(both d, each 2 H, 4ꢀMeC6H4, J = 7.9 Hz); 7.80—7.50 (m, 5 H,
Ph); 4.14 (q, 2 H, OCH2, J = 7.3 Hz); 2.35 (s, 3 H, 4ꢀMeC6H4);
0.93 (t, 3 H, MeCH2, J = 7.3 Hz). 1H NMR (DMSOꢀd6), δ:
10.95, 9.57 (both br.s, each 1 H, NH2); 7.90—7.32 (m, 9 H,
Ph, 4ꢀMeC6H4); 7.33 (s, 1 H, H(5)); 4.20 (q, 2 H, OCH2,
J = 7.3 Hz); 2.39 (s, 3 H, 4ꢀMeC6H4); 0.98 (t, 3 H, MeCH2,
J = 7.3 Hz).
4ꢀAminoꢀ6ꢀ(4ꢀchlorophenyl)ꢀ3ꢀethoxycarbonylꢀ2ꢀphenylꢀ
pyrylium chloride (11c). Yield 91% (A), 79% (B), m.p.
187—188 °C (dec.). Found (%): C, 61.71; H, 4.43; Cl, 18.35;
N, 3.47. C21H17Cl2NO3. Calculated (%): C, 61.55; H, 4.39;
Cl, 18.17; N, 3.59. MS, m/z: 353 [M – HCl]+. IR (KBr), ν/cm–1
:
3328 nar (free NH); 3080 br (bound NH); 1696, 1656.
IR (CHCl3), ν/cm–1: 3368 (NH); 3070 (NH); 1712, 1655, 1498.
1H NMR (CDCl3), δ: 12.32, 9.17 (both br.s, each 1 H, NH2);
8.63 (s, 1 H, H(5)); 7.97, 7.46 (both d, each 2 H, 4ꢀClC6H4,
J = 8.5 Hz); 7.75—7.50 (m, 5 H, Ph); 4.18 (q, 2 H, OCH2,
J = 7.0 Hz); 0.76 (t, 3 H, Mе, J = 7.0 Hz). 1H NMR (DMSOꢀd6),
δ: 10.98, 9.73 (both br.s, each 1 H, NH2); 7.95, 7.63 (both d,
each 2 H, 4ꢀClC6H4, J = 8.5 Hz); 7.87 (s, 1 H, H(5)); 7.80—7.67
(m, 5 H, Ph); 4.21 (q, 2 H, OCH2, J = 7.0 Hz); 0.98 (t, 3 H, Mе,
J = 7.0 Hz). 13C NMR (CDCl3), δ: 171.24, 164.15, 163.43,
161.31, 140.72, 133.56, 131.59, 130.42, 129.53, 129.37, 128.84,
127.07, 108.11, 104.07, 63.67 (OCH2), 13.68 (Me).
4ꢀAminoꢀ3ꢀbutoxycarbonylꢀ2,6ꢀdiphenylpyrylium chloride
(12a). Yield 94% (A), m.p. 173—174 °C (dec.). Found (%):
C, 69.02; H, 5.93; Cl, 9.44; N, 3.55. C22H21ClNO4. Calcuꢀ
lated (%): C, 68.84; H, 5.78; Cl, 9.24; N, 3.65. MS, m/z: 347
[M – HCl]+. IR (KBr), ν/cm–1: 3400 (NH); 3190 (NH); 1720.
1H NMR (DMSOꢀd6), δ: 11.34, 9.72 (both br.s, each 1 H,
NH2); 8.17 (s, 1 H, H(5)); 7.90—7.50 (m, 10 H, 2 Ph); 4.14 (t,
2 H, OCH2, J = 6.4 Hz); 1.38—0.60 (m, 7 H, CH2CH2Me).
1H NMR (CDCl3), δ: 12.63, 8.99 (both br.s, each 1 H, NH2);
8.67 (s, 1 H, H(5)); 7.90—7.35 (m, 10 H, 2 Ph); 4.21 (t, 2 H,
OCH2, J = 6.4 Hz); 1.25—0.59 (m, 7 H, CH2CH2Me). 13C NMR
(CDCl3), δ: 171.06, 164.43, 164.30, 161.28, 134.08, 133.41,
131.58, 129.93, 129.51, 129.25, 128.44, 127.36, 107.92, 103.67,
67.30 (OCH2), 30.02, 19.00, 13.85 (Me).
4ꢀAminoꢀ3ꢀbenzoylꢀ6ꢀ(4ꢀchlorophenyl)pyranꢀ2ꢀone (10c).
Yield 58%, m.p. 271—272 °C (EtOH). Found (%): C, 66.30;
H, 3.62; Cl, 11.04; N, 4.40. C18H12NO3. Calculated (%):
C, 66.37; H, 3.71; Cl, 10.88; N, 4.30. MS, m/z: 325 [M]+.
IR (KBr), ν/cm–1: 3385 nar (free NH); 3223 br (bound NH);
1
1681, 1653 (C=O); 1600, 1510. H NMR (DMSOꢀd6), δ: 9.10,
8.40 (both br.s, each 1 H, NH2); 7.75, 7.60 (both d, each 2 H,
4ꢀClC6H4, J = 7.9 Hz); 7.55—7.30 (m, 5 H, Ph); 6.79 (s, 1 H,
H(5)). 13C NMR (DMSOꢀd6), δ: 196.03 (PhCO); 161.83,
161.36, 160.15, 141.69, 136.62, 131.08, 129.98, 129.82, 128.08,
98.00, 93.61.
4ꢀAminoꢀ3ꢀbenzoylꢀ6ꢀ(4ꢀmethoxyphenyl)pyranꢀ2ꢀone (10d).
Yield 44%, m.p. 215—216 °C (EtOH). Found (%): C, 70.92;
H, 4.65; N, 4.20. C19H15NO4. Calculated (%): C, 71.02; H, 4.71;
N, 4.36. MS, m/z: 321 [M]+. IR (KBr), ν/cm–1: 3385 nar (free
NH); 3230 br (bound NH); 1687, 1650 (C=O); 1590, 1511.
1H NMR (DMSOꢀd6), δ: 9.25, 8.33 (both br.s, each 1 H, NH2);
7.80—7.10 (m, 9 H, Ph, 4ꢀMeOC6H4); 6.67 (s, 1 H, H(5)); 3.75
(s, 3 H, MeO).
4ꢀAminoꢀ6ꢀarylꢀ3ꢀethoxycarbonylꢀ2ꢀphenylpyrylium chloꢀ
rides 11a—c, 12a (general procedure). A. A solution of ketoester
6a—d or 7a (1 mmol) in 5 mL of EtOH and 1 mL of concenꢀ
trated HCl was stirred for 1—2 h. The solvent was distilled off
and the residue was recrystallized from acetone.
B. A mixture of chelate 4a—c or 5a (0.5 mmol) and 1 mL of
concentrated HCl in 5 mL of EtOH was stirred for 2 h. The
solvent was distilled off, the residue was dissolved in 10 mL of
CHCl3, and the organic layer was washed with water (3×20 mL)
and dried over CaCl2. The solvent was evaporated and the resiꢀ
due was recrystallized from acetone and dried.
Ethyl 4ꢀaminoꢀ6ꢀarylꢀ2ꢀphenylpyridineꢀ3ꢀcarboxylates
13a—c (general procedure). A mixture of ketoester 6a—c
(1 mmol), AcOH (4 mL), and NH4OAc (6.4 mmol) was reꢀ
fluxed for 3 h. The solvent was evaporated, and 3 mL of concenꢀ
trated aqueous NH3 and 15 mL of H2O were added to the
residue. The precipitated crystals were filtered off, washed with
water (2×10 mL), and recrystallized from heptane.
4ꢀAminoꢀ3ꢀethoxycarbonylꢀ2,6ꢀdiphenylpyrylium chloride
(11a). Yield 87% (A), m.p. 197—198 °C (dec.). Found (%):
C, 67.30; H, 5.27; Cl, 10.12; N, 3.81. C20H18ClNO3. Calcuꢀ
lated (%): C, 67.51; H, 5.10; Cl, 9.96; N, 3.94. MS, m/z: 319
[M – HCl]+. IR (KBr), ν/cm–1: 3410 (NH); 3185 (NH); 1740
(C=O). 1H NMR (CDCl3), δ: 12.80, 9.00 (both s, each 1 H,
NH2); 8.76 (s, 1 H, H(5)); 8.00—7.50 (m, 10 H, 2 Ph); 4.17 (q,
2 H, OCH2, J = 7.3 Hz); 0.84 (t, 3 H, Mе, J = 7.3 Hz).
4ꢀAminoꢀ3ꢀethoxycarbonylꢀ6ꢀ(4ꢀmethylphenyl)ꢀ2ꢀpheꢀ
nylpyrylium chloride (11b). Yield 89% (A), 78% (B), m.p.
183—184 °C (dec.). Found (%): C, 67.99; H, 5.50; Cl, 9.99;
N, 3.67. C21H20ClNO3. Calculated (%): C, 68.20; H, 5.45; Cl,
Ethyl 4ꢀaminoꢀ2,6ꢀdiphenylpyridineꢀ3ꢀcarboxylate (13a).
Yield 75%, m.p. 108—109 °C (heptane). Found (%): C, 75.26;
H, 5.75; N, 8.89. C20H18N2O2. Calculated (%): C, 75.45;
H, 5.70; N, 8.80. MS, m/z: 318 [M]+. IR (KBr), ν/cm–1: 3470,
3370 (NH); 1669, 1625, 1540. IR (CHCl3), ν/cm–1: 3500, 3390
(NH); 1690, 1610, 1587, 1560. 1H NMR (CDCl3), δ: 7.99—6.90
(m, 10 H, 2 Ph); 6.87 (s, 1 H, H(5)); 5.71 (br.s, 2 H, NH2); 4.00
(q, 2 H, OCH2, J = 6.9 Hz); 0.81 (t, 3 H, Me, J = 6.9 Hz).
13C NMR (CDCl3), δ: 169.65 (C=O); 161.89, 157.97, 155.42,
143.01, 139.30, 131.60—126.50 (CH arom.); 108.69, 107.80 (d,
H(5), J = 152 Hz); 61.30 (t, OCH2, J = 151 Hz); 13.21 (q, Me,
J = 127 Hz).
9.59; N, 3.79. MS, m/z: 333 [M – HCl]+. IR (KBr), ν/cm–1
3390 (NH); 3180 (NH); 1736, 1644, 1472. IR (CHCl3), ν/cm–1
:
:
Ethyl 4ꢀaminoꢀ6ꢀ(4ꢀmethylphenyl)ꢀ2ꢀphenylpyridineꢀ3ꢀcarbꢀ
oxylate (13b). Yield 81%, m.p. 115—116 °C (heptane).

2062
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 9, September, 2003
Dorokhov et al.
Found (%): C, 75.66; H, 5.97; N, 8.49. C21H20N2O2. Calcuꢀ
lated (%): C, 75.88; H, 6.06; N, 8.43. MS, m/z: 332 [M]+.
IR (KBr), ν/cm–1: 3472, 3368 (NH); 1672, 1624, 1544.
IR (CHCl3), ν/cm–1: 3512, 3392 (NH); 1688, 1608, 1584, 1568.
1H NMR (CDCl3), δ: 7.93, 7.25 (both d, each 2 H, 4ꢀMeC6H4,
J = 7.9 Hz); 7.70—7.38 (m, 5 H, Ph); 6.93 (s, 1 H, H(5)); 5.65
(br.s, 2 H, NH2); 4.00 (q, 2 H, OCH2, J = 7.0 Hz); 2.40 (s, 3 H,
4ꢀMeC6H4); 0.80 (t, 3 H, MeCH2, J = 7.0 Hz). 13C NMR
(CDCl3), δ: 169.89 (C=O); 162.00, 158.16, 155.52, 143.33,
140.00, 136.67, 129.94, 129.58, 129.15, 128.68, 128.49, 127.16,
108.73, 105.57, 61.30 (OCH2); 22.00 (4ꢀMeC6H4); 13.80 (Me).
Ethyl 4ꢀaminoꢀ6ꢀ(4ꢀchlorophenyl)ꢀ2ꢀphenylpyridineꢀ3ꢀ
carboxylate (13c). Yield 83%, m.p. 119—120 °C (heptane).
Found (%): C, 68.06; H, 4.91; Cl, 10.26; N, 8.05.
C20H17ClN2O2. Calculated (%): C, 68.09; H, 4.86; Cl, 10.04;
N, 7.94. MS, m/z: 352 [M]+. IR (KBr), ν/cm–1: 3472 (NH);
3368 (NH); 1684, 1604, 1576, 1568. IR (CHCl3), ν/cm–1: 3512
References
1. V. A. Dorokhov, S. V. Baranin, A. Yu. Yagodkin, V. S.
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1
(NH); 3392 (NH); 1688, 1608, 1604, 1568. H NMR (CDCl3),
δ: 7.95—7.39 (m, 9 H, Ph, 4ꢀClC6H4); 6.91 (s, 1 H, H(5)); 5.67
(s, 2 H, NH2); 4.00 (q, 2 H, OCH2, J = 7.0 Hz); 0.81 (t, 3 H,
Me, J = 7.0 Hz).
8. R. W. Hay and D. E. R. Hook, Austr. J. Chem., 1964, 17, 601.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 00ꢀ03ꢀ
32751a).
Received May 23, 2003