Synthesis of unsymmetrical β-arylaminoketones

Article abstract of DOI:10.1023/B:RUGC.0000042429.06729.93

Azomethines derived from aniline were condensed with acetophenone derivatives to obtain new unsymmetrical β-arylaminoketones.

Full text of DOI:10.1023/B:RUGC.0000042429.06729.93

Russian Journal of General Chemistry, Vol. 74, No. 6, 2004, pp. 926 932. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 6, 2004,
pp. 1003 1008.
Original Russian Text Copyright
2004 by Kozlov, Basalaeva.
Synthesis of Unsymmetrical -Arylaminoketones
N. G. Kozlov and L. I. Basalaeva
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Received April 19, 2002
Abstract Azomethines derived from aniline were condensed with acetophenone derivatives to obtain new
unsymmetrical -arylaminoketones.
It follows from published data that -arylamino-
ketones are quite active local anesthetics [1]. They
serve as starting materials in the synthesis of pyra-
zolines [2] and compounds that exhibit bronchodilatat-
ing and hypotensive properties [3]. As known, biolo-
gical activity of compounds is closely related to their
steric structure. Therewith, asymmetry is an indis-
pensable attribute of most biomolecules [4].
Aminoketones has first been prepared by reactions
of benzylideneaniline, benzylidene-p-toluidine, and
benzylidene-p-nitroaniline with dibenzyl ketone and
deoxybenzoine [5]. Later on benzylideneaniline was
condensed with acetophenone and p-methoxyaceto-
phenone [6]. All the cited reactions were performed
in the absence of alkali.
Kozlov et al. [7 9] has synthesized -arylamino-
ketones from hydrochlorides of primary amines
incorporated into Schiff bases, in sealed ampules.
The present work reports on the synthesis of amino-
ketones by condensation of azomethines derived
aniline and substitutes anilines with acetophenone and
halo-, hydroxy-, and nitro-substituted acetophenones
in alcoholic solution under heating.
In the present work we have synthesized new un-
symmetrical -arylaminoketones in alcoholic solu-
tions at atmospheric pressure in the presence of a
catalytic amount of hydrochloric acid.
R
R
O
R
R
1
+
HN
N
O
CH3
R
R
Ia Iw
IIa IIg
IIIa IIIj, IVa IVc, Va Vc,
VIa VIf, VIIa VIIf, VIIIa VIIId,
IXa IXg
R
R
O
Xa Xg
I, R = H (a e), R = H (a), 4-F (b), 4-Cl (c), 4-OCH3 (d), 4-N (CH3)2 (e); R = 4-F (f, g), R = H (f), 4-OCH3 (g); R =
2-CH3, R = H (h); R = 4-CH3 (i k), R = H (i), 4-Cl (j), 4-OH (k); R = 4-OCH3, R = H (l); R = 4-COOH (m o), R = H
(m), 4-Br (n), 4-NO2 (o); R = 4-CH3OCO (p, q), R = H (p), 4-OCH3 (q); R = 4-C2H5OCO (r v), R = H (r), 4-Br (s),
4-OH (t), 2-OCH3 (u), 2,4-di-OH (v). II, R = H (a), 4-Cl (b), 4-Br (c), 4-OH (d), 2-OH (e), 4-NO2 (f), 3-NO2 (g). X,
R = H (a c), R = 4-Cl (a), 4-Br (b), 4-NO2 (c); R = 4-Br (d, e), R = H (d), 4-NO2 (e); R = 4-NO2 (f, g), R = H
(f), 4-NO2 (g).
1070-3632/04/7406-0926 2004 MAIK Nauka/Interperiodica

SYNTHESIS OF UNSYMMETRICAL -ARYLAMINOKETONES
927
Presunably, the action of the catalyst consists in
that its proton adds to the nitrogen atom of the Schiff
base, thus polarizing the azomethine bond and increas-
ing the positive charge on the carbon atom. Ap-
parently, simultaneous protonation of the aceto-
phenone molecule takes place, resulting in a typical
nucleophilic addition [reaction (1)].
the strongest C=N polarization. In this case, the
synthesis of -arylaminoketones occurs under heating
within 5 15 min. The yield of the final product of the
reaction depends on its duration. The reactions of N-
(p-bromobenzylidene)anesthesin (Is) with aceto-
phenone (IIa) or p-nitroacetophenone (IIf) give
-
arylaminoketones IXb or IXc after 15-min heating.
In the same reagent mixtures heated for 30 min,
4-bromochalcones Xd or Xe are formed [reaction (2)].
The reactions of N-benzylidene-p-carboxyaniline (Im)
with 4-Cl- or 4-Br-acetophenones (IIb, IIc) are even
more sensitive: They yield -arylaminoketones after
5-min heating and result in exclusive formation of
unsaturated ketones Xa or Xb after 15-min heating.
+
N
CH
>
R
^
R
We made use of the following aniline derivatives:
p-fluoroaniline, o- and p-toluidines, p-anisidine, and
p-aminobenzoic acid and its methyl and ethyl (ane-
sthesin) esters. The electron density distributions in
azomethines Ia Iv show that the activity of the azo-
methine bond is directly related to the nature of sub-
stitution in the benzene ring of the amine or aldehyde.
As the electron-donor power of the substituent in the
aniline moiety increases (in going from CH3 to OCH3
and C2H5OCO), the yield of condensation products
decreases. Thus, the reaction of acetophenone (IIa)
with N-benzylidene-p-toluidine (Ii) provides 68% of
phenyl -phenyl- -(p-toluidino)ethyl ketone (Va),
whereas the yield of phenyl -phenyl- -[p-(ethoxy-
carbonyl)phenylamino]ethyl ketone (IXa) in the reac-
tion of acetophenone with benzylidene[p-(ethoxycar-
bonyl)phenyl]amine (Ir) is 43%. Strong electron-
donor substituents, donating electrons to the benzene
ring and entering in conjugation with the whole
system, affect slightly the steady-state electron density
by decreasing the additional positive charge on the
carbon atom. The yield of -arylaminoketones also
decreases with increasing electron-donor power of R .
Attempted condensation of N-[p-(dimethylamino)-
benzylidene]aniline (Ie) with acetophenone under the
conditions studied failed. By the same reason, we
failed to effect condensation of ethyl N-(p-hydroxy-
benzylidene)-p-aminobenzoate (It) and N-(p-hydroxy-
benzylidene)-p-toluidine (Ik) with p-hydroxyaceto-
phenone (IId), N-(2,4-dihydroxybenzylidene)-p-ane-
sthesin (Iv) with p-chloro- and p-bromoacetophenones
(IIb, IIc). The latter reactions resulted in the recovery
of the starting azomethines.
Thus, we found that the synthesis of -arylamino-
ketones from azomethines and acetophenone and its
derivatives occurs in mild conditions and good yields
if the starting compounds contain electron-acceptor
substituents. If the starting compounds contain elec-
tron-donor substituents, longer heating of the reaction
mixture is required, the yield of final products is
reduced, or the reaction fails to occur at all.
The structure of , -unsaturated ketones Xa Xg
was determined by 1H NMR and IR spectroscopy. The
IR spectra of these compounds contain characteristic
1
absorption bands at 1690 1670 and 1600 1580 cm ,
belonging to C=O and C=C stretching vibrations. The
1H NMR spectra of chalcones Xa Xg show signals of
protons at C1=C2, appearing as doublets at 7.6 and
7.7 ppm, respectively (3J 15 Hz). Such coupling
constant points to a trans structure of the CH=CH
fragment in Xa Xg, since in the cis isomer it should
not be higher than 6 Hz [10].
H
H
O
O
H
Theoretically, chalcones can be formed by two
absolutely independent reactions. First, if the initially
formed -arylaminoketone, provided it contains in the
position to carbonyl an aryl radical which decreases
the electron density on the NH CH bond, undergoes
hydramine cleavage and converts into amine and
chalcone [11]. As also known, in acid medium
-aminoketone takes up proton by the nitrogen lone
electron pair to form an ammonium-like compound,
thus favoring displacement of the electron density to
nitrogen and, as a consequence, cleavage of the
NH CH bond [12]. Second, it can be admitted that
Electron-donor substituents in the ortho position
of the aniline or acetophenone benzene rings act in a
direction opposite to the direction of C=N polarization,
and the positive charge on the carbon atom decreases
so as to prevent condensation of N-benzylidene-o-
toluidine (Ih) with acetophenone and its derivatives.
Electron-acceptor substituents withdraw electrons,
and the resulting electron density distribution favors
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

928
KOZLOV, BASALAEVA
Schiff bases are hydrolyzed under the reaction condi-
tions, and the aldehyde that forms reacts with ketone
to give the corresponding chalcone whose reaction
with amine yields -arylaminoketone [13]. As shown
in [14], benzalacetone reacts with methyl and ethyl
p-aminobenzoates to form -arylaminoketones whose
physicochemical properties proved identical to those
of -arylaminoketones obtained from Schiff bases and
acetone.
tron impact. The base peak (100%) at m/e 105 belong
to the [C6H5CO]+ ion. The spectra contain [M
C6H5COCH2]+ (26 30%) and [C6H4]+ (40 50%)
fragment ions, as well as molecular ions M+ (10 15%).
1
The H NMR spectra of the alkylphenyl -(alkyl-
anilino)- -(alkylphenyl)ethyl ketones (Table 2) dis-
play signals of protons at C1 and C2, whose multi-
plicity and coupling constants relate to the steric struc-
ture of these compounds. The signals of protons at
C1 are a doublet of doublets at 2.90 3.58 and 3.20
3.80 ppm, respectively. The common geminal coupl-
In our conditions, the reactions of N-(p-nitroben-
zylidene)-p-carboxyaniline (Ip) with acetophenone
(IIa) and p-nitroacetophenone (IIf) are the only that
provide nitrochalcones Xf and Xg, respectively, at any
reaction duration.
ing constant 2J of these compounds is 16.6 Hz.
Moreover, the synthesized -arylaminoketones have
by one vicinal coupling constant with the proton at
C2 (4.50 5.40 ppm, d.d), equal to 5.0 and 10.0 Hz.
As judged from the magnitudes of these constants, the
molecules have a staggered molecular conformation
[10] with slightly distorted dihedral angles. Such
molecular geometry is associated with intramolecular
hydrogen bonding between the carbonyl and amino
groups, which brings them closer together (below is
At the same time, -arylaminoketones are stabi-
lized by electron-donor substituents or hydrogen in
the aromatic nuclei of the aldehyde and acetophenone
moieties, which is explained by the positive inductive
effect [15]. Therefore, in the syntheses of phenyl
-phenyl- (phenylamino)ethyl ketone (IIIa), phenyl
-phenyl- -(p-toluidino)ethyl ketone (Va), or p-
(hydroxyphenyl) -(p-anisidino)- -phenylethyl ketone
(IVc) no , -unsaturated ketones do not form even
on prolonged heating of the reaction mixture.
shown the Newman projection along the C2 C1 bond).
H
H
The structure of -arylaminoketones IIIa IIIj,
IVa IVc, Va Vc, VIa VIf, VIIa VIIf, VIIIa VIIId,
and IXa IXg was proved by H NMR and IR spec-
troscopy and GC MS. The melting points, yields, and
elemental analyses are given in Table 1.
2
O
1
H
N
H
The IR spectra revealed an H-bonded secondary
amino group (band near 3450 3220 cm with fine
EXPERIMENTAL
1
structure) and a carbonyl group (band near 1650
The IR spectra were registered on a Nicolet Protege-
460 spectrophotometer. The H NMR spectra were
run on Bruker DRX-500 (500 Hz) or Tesla BS-567A
(100 MHz) spectrometers for 2 5% solutions in
DMSO-d6, internal reference TMS. The mass spectra
were run on a FINNIGAN-MAT INCOS-50 instru-
ment (electron impact, 70 eV).
1
1
1620 cm ). Compounds IIId and IVa IVc give a
1
strong absorption band at 1120 1100 cm , belonging
to stretching vibrations of the C F bond, compounds
IIIc, IIIe, IIIg, Vb, VIb, and VIIb, a C Cl band at
1
860 830 cm , and compounds IIIb, IIIh, VIc, VIIc,
VIIf, IXb, IXc, IXe, and IXg, a C Br band at 580
1
570 cm . A strong OCH3 absorption band at 2880
1
Methyl and ethyl p-aminobenzoates were pre-
pared from p-aminobenzoic acid and corresponding
alcohol in the presence of sulfuric acid with isolation
of p-alkoxycarbonylphenylammonium sulfate [17].
2840 cm is observed in the spectra of compounds
IIIf IIIj, IVb, IVc, VIa VIf, VIIId, IXf, and IXg,
and compounds IIIi, IIIj, Vc, VIe, VIf, VIId, VIIIb,
1
and IXc give bands at 1380 1360 and 1550 1530 cm ,
assignable to symmetric and antisymmetric N O
Arylidenealkylanilines Ia Iv were prepared by
the reaction of aniline derivatives with benzaldehyde
derivatives in alcohol by the standard procedure [18].
stretching vibrations. Compounds VIIIa VIIId and
1
IXa IXg give a strong band at 1600 1530 cm ,
associated with asymmetric vibrations of CH3CO2 or
C2H5CO2 carboxylate ions.
-Anilino- -phenylethyl phenyl ketone (IIIa). A
solution of 0.01 of acetophenone (IIa) in 10 ml of al-
cohol and 3 drops of conc. HCl acid were added to a
solution of 0.01 mol of benzylideneaniline (IIa) in
15 ml of alcohol heated on a water bath. The reaction
mixture was heated for 30 min. After cooling, the
The mass spectra of alkylphenyl -(alkylanilino)- -
(alkylphenyl)ethyl ketones IIIa IIIj, IVa IVc, Va
Vc, VIa VIf, VIIa VIIf, VIIIa VIIId, and IXa IXg
show that these compounds are unstable under elec-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

SYNTHESIS OF UNSYMMETRICAL -ARYLAMINOKETONES
929
Table 1. Yields, melting points, and elemental analyses of alkylphenyl -(alkylanilino)- -(alkylphenyl)ethyl ketones
IIIa IIIj, IVa IVc, Va Vc, VIa VIf, VIIa VIIf, and IXa IXg
Found, %
N (Hlg)
54 170 171a 83.70 6.28 4.67
Calculated, %
N (Hlg)
83.72 6.31 4.65
R
R
R
mp,
C
Formula
C
H
C
H
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
H
H
H
H
H
H
H
H
H
H
H
H
H
H
C21H19NO
4-Br
4-Cl
H
62 140 141 66.30 4.70 3.70(21.00) C21H18BrNO 66.32 4.74 3.68(21.05)
65 112 113a 75.21 5.38 4.15(10.53) C21H18ClNO 75.22 5.36 4.18(10.57)
4-F
4-Cl
4-OCH3
4-OCH3 4-Cl
4-OCH3 4-Br
60 111 112
4.32(5.94) C21H18FNO
78.99 5.64 4.38(5.96)
H
H
67 116 117a 75.22 5.34 4.19(10.60) C21H18ClNO 75.22 5.36 4.18(10.57)
63 160
66 135a
65 133
79.80 6.32 4.28
72.20 5.42 3.80(9.80) C22H20ClNO2 72.13 5.46 3.83(9.84)
64.42 4.91 3.38(19.47) C22H20BrNO2 64.40 4.88 3.41(19.51)
C22H21NO2
79.76 6.34 4.23
4-OCH3 4-NO2 60 169 170 70.20 5.34 7.45
4-OCH3 3-NO2 58 142 144 70.23 5.31 7.42
C22H20N2O4 70.21 5.32 7.45
C22H20N2O4 70.21 5.32 7.45
IIIj
IVa 4-F
IVb 4-F
IVc 4-F
H
H
H
80 250 252
75 125
4.35(6.01) C21H18FNO
4.00(5.43) C22H20FNO2 75.64 5.73 4.01(5.44)
3.84(5.16) C22H20FNO3 72.32 5.48 3.84(5.20)
78.99 5.64 4.38(5.96)
4-OCH3
4-OCH3 2-OH 52 230
H
4-Cl
H
H
H
H
H
Va
Vb
Vc
4-CH3
4-CH3
4-CH3
H
H
68 171a
83.78 6.63 4.47
C22H21NO
83.80 6.66 4.45
70 152 153 75.40 5.60 4.98(10.25) C22H20ClNO 75.43 5.71 4.00(10.28)
4-NO2 53 161 162 73.30 5.55 7.80
H
4-Cl
4-Br
4-OH 42 153
C22H20N2O3 73.33 5.56 7.78
C22H21NO2 79.76 6.34 4.23
VIa 4-OCH3
VIb 4-OCH3
VIc 4-OCH3
VId 4-OCH3
VIe 4-OCH3
45 149a
59 127
52 136
79.74 6.30 4.25
72.10 5.42 3.80(9.80) C22H2OClNO2 72.13 5.46 3.83(9.84)
64.44 4.85 3.40(19.48) C22H2OBrNO2 64.40 4.88 3.41(19.51)
76.05 6.03 4.06
C22H21NO3
76.08 6.05 4.03
H
H
4-NO2 48 138 140 70.20 5.29 7.47
3-NO2 51 144 145 70.23 5.30 7.44
C22H2ON2O4 70.21 5.32 7.45
C22H2ON2O4 70.21 5.32 7.45
VIf
4-OCH3
VIIa 4-COOH
VIIb 4-COOH
VIIc 4-COOH
VIId 4-COOH
VIIe 4-COOH
VIIf 4-COOH
VIIIa 4-CH3OCO
VIIIb 4-CH3OCO
VIIIc 4-CH3OCO
VIIId 4-CH3OCO 4-CH3O H
IXa 4-C2H5OCO H
IXb 4-C2H5OCO 4-Br
IXc 4-C2H5OCO 4-Br
IXd 4-C2H5OCO 4-OH
IXe 4-C2H5OCO 4-OH
H
H
H
H
H
4-Br
H
H
H
H
4-Cl
4-Br
60 212
65 200 201 69.44 4.78 3.65(9.43) C22H18ClNO3 69.47 4.74 3.68(9.47)
61 180 62.25 4.23 3.28(18.85) C22H18BrNO3 62.26 4.25 3.30(18.87)
C22H18N2O5 67.69 4.62 7.18
C22H19NO4 73.13 5.26 3.88
47 165 166 62.26 4.25 3.32(18.86) C22H18BrNO3 62.26 4.25 3.30(18.87)
51 186a
76.87 5.83 3.90 C23H21NO3 76.88 5.85 3.89
C23H20N2O5 68.32 4.95 6.93
76.50 5.49 4.03
C22H19NO3
76.52 5.51 4.06
4-NO2 50 131 132 67.69 4.61 7.16
2-OH 43 172 173 73.25 5.24 3.90
H
H
4-NO2 43 160 161 68.31 4.93 6.92
2-OH 38 153
73.59 5.57 3.73
C23H21NO4
C24H23NO4
C24H23NO3
73.60 5.60 3.73
74.04 5.91 3.60
77.21 6.17 3.75
45 163a
74.01 5.92 3.61
H
H
43 149 150a 77.20 6.15 3.78
62 145a
63.73 4.90 3.10(17.69) C24H22BrNO3 63.72 4.87 3.09(17.70)
4-NO2 40 169 170 57.95 4.21 5.62(16.09) C24H21BrN2O5 57.94 4.23 5.63(16.10)
H
4-Br
H
35 178
37 147 148 61.52 4.71 2.96(17.10) C24H22BrNO4 61.54 4.70 2.99(17.09)
39 123 74.47 6.23 3.42 C25H25NO4 74.44 6.21 3.46
41 165 166 62.10 5.19 2.93(16.58) C25H25BrNO4 62.11 5.17 2.90(16.56)
74.00 5.92 3.58
C24H23NO4
74.04 5.91 3.60
IXf
4-C2H5OCO 2-OCH3
IXg 4-C2H5OCO 2-OCH3 4-Br
a
The melting points are consistent with those reported in [7] (IIIa, Va, VIa), [14] (IIIa, Va, VIa), [16] (IIIc, IIIe, IIIg), and [11]
(IXb).
precipitate that formed was filtered off, treated with
aqueous ammonia for neutralization, and recrystallized
from alcohol toluene. Alkylphenyl -(alkylanilino)- -
(alkylphenyl)ethyl ketones IIIb IIIj, IVa IVc, Va
Vc, VIa VIf, VIIa, VIIe, VIIf, VIIIa VIIId, IXa,
and IXd IXg were prepared in a similar way.
-(p-Carboxyanilino)- -phenylethyl p-chloro-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

930
KOZLOV, BASALAEVA
1
Table 2. H NMR spectra of alkylphenyl -(alkylanilino)- -(alkylphenyl)ethyl ketones IIIa IIIj, IVa IVc, Va Vc, VIa
VIf, VIIa VIIf, and IXa IXg, , ppm (J, Hz)
C1 H,
d.d
C1 H,
d.d
C21 H,
d.d
Aromatic and R, R , R protons
NH
(3J 5.0, (3J 10.0, (3J 5.0,
(2J 16.6) (2J 16.6) (2J 10.0)
IIIa
IIIb
3.23
3.23
3.50
3.60
5.00
4.97
6.40 t, 6.52 d (9.6), 7.00 d (8.3), 7.20 7.50 m, 7.80 8.00 m 6.30 d (8.4)
6.42 t, 6.45 d (9.7), 6.93 d (9.9), 7.25 t, 7.65 d (10.0), 7.48 d 6.45 d (8.6)
(9.8), 7.80 t, 7.85 d (9.7), 8.03 d (10.0)
IIIc
IIId
3.18
3.20
3.45
3.60
4.85
5.00
6.40 t, 6.50 d (9.8), 6.90 d (8.0), 7.20 t, 7.65 d (9.8), 7.80 d 6.35 d (8.0)
(9.8), 7.85 t, 7.90 d (9.6), 8.00 d (9.8)
6.40 6.60 m, 6.90 7.20 m, 7.40 7.60 m, 7.90 d (9.6), 8.00 d 6.20 d (9.8)
(10.1)
IIIe
IIIf
3.25
3.28
3.53
3.60
4.96
4.95
6.40 t, 6.50 d (9.6), 7.05 d (8.0), 7.20 7.45 m, 7.70 8.00 m 6.25 d (8.2)
3.75 s (3H, OCH3), 6.45 t, 6.50 d (10.0), 6.80 d (10.0), 6.95 t, 6.00 d (8.8)
7.35 d (9.0), 7.50 t, 7.70 t, 7.95 d (13.3)
IIIg
IIIh
IIIi
IIIj
IVa
IVb
IVc
Va
3.58
3.55
2.90
3.15
3.27
3.30
3.40
3.20
3.50
3.40
3.30
3.25
3.20
3.10
2.90
3.00
3.65
3.70
3.30
3.50
3.63
3.67
3.58
3.57
3.60
3.70
3.65
3.60
3.65
3.50
3.30
3.20
4.40
4.90
4.90
4.80
5.00
4.90
4.96
4.95
4.50
4.60
4.50
4.75
4.65
4.95
4.90
4.90
3.70 s (3H, OCH3), 6.50 d (7.9), 6.80 d (8.0), 6.95 t, 7.35 d 6.03 d (8.1)
(8.2), 7.55 t, 7.90 d (10.0), 8.15 d (11.3)
3.75 s (3H, OCH3), 6.50 t, 6.85 d (8.0), 7.00 t, 7.35 d (8.2), 5.98 d (8.7)
7.70 t, 7.85 d (9.3), 8.05 d (10.8)
3.65 s (3H, OCH3), 6.40 6.60 m, 6.85 7.20 m, 7.45 t, 7.60 t, 6.20 d (8.9)
8.00 d (9.6)
3.85 s (3H, OCH3), 6.50 d (9.7), 6.70 d (8.1), 7.00 t, 7.30 d 6.10 d (9.1)
(8.8), 7.75 t, 8.10 t, 8.25 d (9.6)
6.30 t, 6.52 d (9.8), 6.90 t, 7.05 t, 7.40 7.50 m, 7.60 t, 7.93 d 6.18 d (8.9)
(10.2)
3.70 s (3H, OCH3), 6.40 t, 6.50 d (10.0), 6.70 6.90 m, 7.30
7.50 m, 7.90 d (9.7), 8.00 8.10 m
6.05 d (8.6)
3.70 s (3H, OCH3), 6.20 6.50 m, 6.70 7.00 m,7.50 t, 7.70 t, 6.15 d (8.3)
8.05 d (9.0), 9.30 s (1H, OH)
2.10 s (3H, CH3), 6.40 t, 6.58 d (9.8), 6.80 d (9.8), 6.90 t,
7.30 d (9.2), 7.50 t, 7.95 d (13.0)
6.0 d (8.8)
Vb
2.05 s (3H, CH3), 6.45 t, 6.52 d (9.6), 6.70 d (9.5), 6.85 t, 6.15 d (8.0)
7.25 d (9.0), 7.55 t, 7.90 d (13.0)
2.15 s (3H, CH3), 6.30 6.60 m, 6.70 7.10 m, 7.30 d (9.0), 6.00 d (8.0)
7.60 t, 7.90 d (13.0)
3.70 s (3H, OCH3), 6.50 t, 6.58 d (10.0), 6.75 d (10.0), 6.90 t, 6.05 d (8.2)
7.40 d (9.0), 7.50 t, 7.60 t, 7.90 d (13.0)
3.65 s (3H, OCH3), 6.40 t, 6.50 d (10.0), 6.70 d (10.0), 6.90 t, 6.10 d (8.3)
7.40 d (9.0), 7.50 t, 7.60 t, 7.85 d (12.8)
3.70 s (3H, OCH3), 6.40 6.70 m, 6.90 7.50 m, 7.65 t, 7.90 d 6.05 d (8.5)
(12.0)
3.75 s (3H, OCH3), 6.10 6.40 m, 6.60 7.10 m, 7.40 t, 7.70 t, 6.00 d (8.0)
8.00 d (9.0), 9.20 s (1H, OH)
3.65 s (3H, OCH3), 6.40 6.60 m, 6.85 7.20 m, 7.45 t, 7.60 t, 6.20 d (8.7)
8.00 d (9.0)
3.60 s (3H, OCH3), 6.30 6.55 m, 6.80 7.10 m, 7.40 t, 7.65 t, 6.10 d (8.5)
8.40 d (9.0)
Vc
VIa
VIb
VIc
VId
VIe
VIf
VIIa
VIIb
3.30
3.25
3.80
3.60
5.20
5.10
7.20 7.60 m, 7.90 d (9.7), 8.00 8.10 m, 11.90 br.s (1H, COOH) 6.50 d (9.0)
6.48 d (9.7), 7.10 t, 7.30 t, 7.40 d (8.0), 7.48 d (8.3), 7.53
7.60 m, 7.90 d (8.0), 12.00 br.s (1H, COOH)
6.30 d (8.6)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

SYNTHESIS OF UNSYMMETRICAL -ARYLAMINOKETONES
931
Table 2. (Contd.)
C1 H,
d.d
C1 H,
d.d
C21 H,
d.d
Aromatic and R, R , R protons
NH
(3J 5.0, (3J 10.0, (3J 5.0,
(2J 16.6) (2J 16.6) (2J 10.0)
VIIc
VIId
VIIa
VIIb
VIIIa
VIIIb
VIIIc
VIIId
IXa
3.30
3.43
3.30
3.20
3.35
3.40
3.30
3.40
3.40
3.35
3.20
3.40
3.60
3.80
3.70
3.50
3.70
3.55
3.60
3.50
3.60
3.50
3.50
3.60
5.10
5.20
5.10
4.30
5.10
5.10
5.20
5.00
5.10
5.00
5.10
5.40
6.45 d (9.5), 7.00 t, 7.25 t,7.40 d (8.0), 7.50 d (8.0), 7.50
7.60 m, 7.90 d (8.0), 12.00 br.s (1H, COOH)
6.45 d (9.3), 7.20 t, 7.40 t, 7.48 d (8.7), 7.60 d (6.0), 8.10 t, 6.70 d (9.2)
8.30 d (8.0), 11.50 br.s (1H, COOH)
6.60 d (9.8), 7.20 t, 7.30 8.00 m, 10.0 s (1H, OH), 11.2 br.s 6.30 d (9.7)
(1H, COOH)
6.30 d (9.0), 6.50 t, 5.90 6.30 m, 6.45 d (8.8), 7.10 7.30 m, 6.20 d (8.8)
10.20 br.s (1H, COOH)
3.70 s (3H, OCH3), 6.55 d (13.2), 7.20 t, 7.30 t, 7.45 d (7.8), 6.95 d (10.0)
7.50 t, 7.60 d (9.5), 7.95 d (10.0)
3.70 s (3H, OCH3), 6.55 d (8.6), 7.10 t, 7.40 t, 7.60 d (8.0), 6.95 d (8.3)
7.90 d (8.4), 8.18 d (8.8), 8.35 d (9.0)
3.70 s (3H, OCH3), 6.50 d (8.5), 7.10 t, 7.35 t, 7.60 d (8.0), 6.90 d (8.7)
7.90 d (8.0), 8.20 d (8.7), 8.35 d (9.0), 9.8 s (1H, OH)
3.60 s (6H, 2OCH3), 6.40 d (8.3), 7.00 t, 7.40 t, 7.65 d (8.0), 6.60 d (8.4)
7.90 d (8.0), 8.20 d (8.5), 8.30 d (9.0)
1.30 t (3H, OCH2CH3), 4.15 q (2H, OCH2CH3), 6.60 d (9.0), 6.48 d (8.0)
7.20 7.40 m, 7.90 8.05 m
6.50 d ‘(8.4)
IXb
1.30 t (3H, OCH2CH3), 4.10 q (2H, OCH2CH3), 6.50 d (9.0), 6.57 d (8.4)
7.10 7.50 m, 7.90 8.10 m
1.32 t (3H, OCH2CH3), 4.30 q (2H, OCH2CH3), 6.50 t, 7.20
7.50 m, 7.70 7.90 m
1.30 t (3H, OCH2CH3), 4.18 q (2H, OCH2CH3), 6.70 t, 6.80
7.00 m, 7.10 7.40 m, 7.50 7.70 m, 7.90 t, 7.98 d (9.0), 9.05 s
IXc
6.47 d (8.2)
6.30 d (8.1)
(1H, OH)
IXd
IXe
IXf
IXg
3.22
3.25
3.30
3.60
3.40
3.65
5.35
5.30
5.40
1.30 t (3H, OCH2CH3), 4.20 q (2H, OCH2CH3), 6.50 d (7.40), 6.50 d (8.0)
6.65 d (9.3), 7.20 d (5.6), 7.60 7.75 m, 7.85 d (7.4), 8.90 s
(1H, OH)
1.25 t (3H, OCH2CH3), 4.18 q (2H, OCH2CH3), 3.90 s (3H, 6.45 d (8.6)
OCH3), 6.60 d (8.1), 6.85 t, 6.93 d (9.5), 7.18 t, 7.35 d (9.1),
7.48 t, 7.57 d (9.0), 7.60 d (10.0)
1.20 t (3H, OCH2CH3), 4.20 q (2H, OCH2CH3), 3.65 s (3H, 6.40 d (8.6)
OCH3), 6.85 t, 6.92 d (8.0), 7.18 t, 7.40 d (8.2), 7.60 7.70 m,
7.90 d (9.0)
phenyl ketone (VIIb). A solution of 0.01 of aceto-
phenone (IIa) in 10 ml of alcohol and 3 drops of conc. mp 101 C (consistent with published data [9]). p-
HCl acid were added to a solution of 0.01 mol of N- Bromophenyl -(p-carboxyanilino)- -phenylethyl
benzylidene-p-carboxyaniline (Im) in 15 ml of alcohol. ketone (VIIc) and 4 -bromochalcone (Xb) (mp 104 C,
lized from alcohol to isolate 4 -chlorochalcone (Xa),
The reaction mixture was heated for 5 min. After
cooling, the crystals that formed were filtered off,
treated with aqueous ammonia, and recrystallized
from alcohol toluene (1:2).
coincides with that reported in [9]) were obtained in
a similar way.
-(p-Bromophenyl)- -[p-(ethoxycarbonylphenyl-
amino)]ethyl p-nitrophenyl ketone (IXc). A solution
of 0.01 mol of p-nitroacetophenone (IIf) in 10 ml of
alcohol and 3 drops of conc. HCl were added to
alcohol solution of 0.01 mol of ethyl N-(p-bromo-
The reaction mixture of the same composition was
heated on a water bath for 15 min. After cooling, the
crystals that formed were filtered off and recrystal-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

932
KOZLOV, BASALAEVA
benzylidene)-p-aminobenzoate (Is). The reaction mix-
ture was heated on a boiling water bath for 15 min.
After cooling, the precipitate that formed was filtered
off, treated with aqueous ammonia, and recrystallized
from alcohol toluene. Phenyl -(p-bromophenyl)- -
[p-(ethoxycarbonylphenylamino)]ethyl ketone (IXb)
and p-nitrophenyl -(p-carboxyanilino)- -phenylethyl
ketone (VIId).
5. Francis, E., J. Chem. Soc., 1902, vol. 79, no. 5, p. 441.
6. Mayer, Ch., Bull. Soc. Chim. Fr., 1916, vol. 19, no. 3,
p. 427.
7. Kozlov, N.S. and Shur, I.A., Zh. Obshch. Khim., 1960,
vol. 30, no. 8, p. 2746.
8. Kozlov, N.S. and Pak, V.D., Zh. Obshch. Khim., 1962,
vol. 32, no. 10, p. 3386.
9. Kozlov, N.S., Pinegina, L.Yu., and Selezneva, E.A.,
The reaction mixture of the same composition was
heated on a boiling water bath for 30 min. After
cooling, the precipitate that formed was filtered off
and recrystallized from alcohol toluene to isolate
4-bromo-4 -nitrochalcone (Xe), mp 125 C. 4-Bromo-
chalcone (Xd), mp 114 C, and 4 -nitrochalcone (Xc),
mp 107 C, were isolated in a similar way.
Zh. Obshch. Khim., 1962, vol. 32, no. 2, p. 436.
10. Gordon, A.J. and Ford, R.A., The Chemist’s Compa-
nion, New York: Wiley, 1972.
11. Kozlov, N.S., Pak, R.D., and Simonova, E.V., Vesci
Akad. Navuk BSSR, Ser. Khim. Navuk, 1968, no. 4,
p. 111.
By the above procedure, from the reaction mixture
of 0.01 mol of N-benzylidene-p-carboxyaniline (Im)
and p-nitroacetophenone (IIf) after 15-min heating
we isolated p-nitrophenyl -(p-carboxyanilino)- -
phenylethyl ketone (VIId) and after 30-min heating,
4-nitrochalcone (Xc), mp 98 C.
12. Porai-Koshits, V.A., Poznanskaya, E.M., Shevchen-
ko, V.S., and Pavlova, L.A., Zh. Obshch. Khim., 1947,
vol. 17, no. 6, p. 1774.
13. Kozlov, N.S. and Abramova, Z.A., Zh. Obshch. Khim.,
1960, vol. 30, no. 7, p. 1595.
14. Kozlov, N.S. and Pak, V.D., Zh. Obshch. Khim., 1960,
vol. 30, no. 7, p. 2400.
REFERENCES
15. Heterocyclic Compounds, Elderfield, R.C., Ed., New
York: Wiley, 1954, vol. 4. Translated under the title
Geterociklicheskie soedineniya, vol. 4, Moscow:
Inostrannaya Literatura, 1955, p. 13.
1. Profft, E., Runge, F., and Jumar, A., J. Prakt. Chem.,
1954, vol. 1, nos. 1 2, p. 57.
2. Ershov, V.V., Kost, A.N., and Terent’ev, A.P., Zh.
Obshch. Khim., 1957, vol. 27, no. 1, p. 258.
16. Pak, V.D., Pinegina, L.Yu., and Simonova, E.V., Tr.
Perm. Gos. S-kh. Inst., 1970, vol. 68, p. 112.
3. Biel, J.H., Schwarz, E.G., Sprengler, E.P., Lei-
ser, H.A., and Friedman, H.L., J. Am. Chem. Soc.,
1954, vol. 76, no. 12, p. 3149.
17. Preparativnaya organicheskaya khimiya (Preparative
Organic Chemistry), Vul’fson, N.S., Moscow: Khi-
miya, 1964, pp. 375 376.
4. Plemenkov, V.V., Vvedenie v khimiyu prirodnykh so-
edinenii (Introduction into the Chemistry of Natural
Compounds), Kazan, 2001.
18. Kozlov, N.G. and Basalaeva, L.I., Zh. Obshch. Khim.,
2001, vol. 71, no. 2, p. 279.
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