Synthesis of β-amino ketones derived from aminobenzoic acids

Article abstract of DOI:10.1134/S1070363217020311

Alkylation of aminobenzoic acids and their derivatives with 3-diethylamino-1-arylpropan-1-one hydrochlorides gave the corresponding β-aminopropiophenones some of which were tested for antioxidant activity.

Full text of DOI:10.1134/S1070363217020311

ISSN 1070-3632, Russian Journal of General Chemistry, 2017, Vol. 87, No. 2, pp. 342–346. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © G.A. Gevorgyan, G.Yu. Khachvankyan, A.G. Agababyan, N.Z. Akopyan, G.A. Panosyan, M.G. Malakyan, 2017, published in
Zhurnal Obshchei Khimii, 2017, Vol. 87, No. 2, pp. 328–332.
LETTERS
TO THE EDITOR
Synthesis of β-Amino Ketones Derived from Aminobenzoic Acids
G. A. Gevorgyana*, G. Yu. Khachvankyana, A. G. Agababyana,
N. Z. Akopyana, G. A. Panosyanb, and M. G. Malakyanc
a Mndzhoyan Institute of Fine Organic Chemistry, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, ave. Azatutyan 26, Yerevan, 0014 Armenia
*e-mail: gyulgev@gmail.com
b Molecular Structure Research Center, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, ave. Azatutyan 26, Yerevan, 0014 Armenia
c Research Center of Radiation Medicine and Burns, Ministry of Health Protection of Armenia,
Davtashen 25a, Yerevan, 0054 Armenia
Received April 7, 2016
Abstract—Alkylation of aminobenzoic acids and their derivatives with 3-diethylamino-1-arylpropan-1-one
hydrochlorides gave the corresponding β-aminopropiophenones some of which were tested for antioxidant
activity.
Keywords: aminobenzoic acid, 3-(4-aminophenylcarboxamido)propanoic acid, β-aminopropiophenone, alkylation
DOI: 10.1134/S1070363217020311
p-Aminobenzoic acid and its derivatives attract
particular interest due to broad spectrum of their
biological activity and low toxicity. Compound based
thereon occupy an important place among medicinal
agents, specifically among local anesthetics; they
enhance resistance to radiation sickness, protect from
UV radiation, exhibit anticoagulant and antioxidant
activity, and inhibit peroxide oxidation of retinal lipids
[1–4]. The synthesis and biological activity of new
functional derivatives of p-aminobenzoic acid have
recently been reported [1, 4]. A large series of β-amino
ketones with pronounced antidiabetic activity have
been synthesized on the basis of the non-steroidal anti-
inflammatory drug nabumetone and p-aminobenzoic
acid [4]. Molecules of these compounds contained two
aromatic rings and carboxy and amino groups. It is also
known that derivatives 2-aminobenzoic (anthranilic) acid
possess anti-inflammatory properties [3, 5, 6].
ethyl 4-aminobenzoate (novocaine), and N-(4-amino-
benzoyl)-β-alanine with 1-aryl-3-diethylaminopropan-
1-one hydrochlorides 1 according to the procedure
described in [7] afforded β-amino ketones 2–21 in 34–
98% yield. The structure of compounds 2–21 was con-
1
firmed by elemental analyses and IR and H spectra
(Scheme 1).
The antioxidant activity of some of the synthesized
β-amino ketones was studied by the photoinduced
chemiluminescence method. Compounds 2 and 7–9
showed antioxidant activity at a concentration of
40 nmol, i.e., their activity was four times lower than
that of 2,6-di-tert-butyl-4-methylphenol (butylated hyd-
roxytoluene) taken as reference drug and considerably
lower than the activity of Trolox (6-hydroxy-2,5,7,8-
tetramethylchroman-2-carboxylic acid).
Initial 1-aryl-3-diethylaminopropan-1-ones hydro-
chlorides 1 were synthesized as described in [8].
On the basis of published data and results of our
studies [7, 8], in this work we propose a synthetic
approach to β-aminopropiophenones containing amino-
benzoic acid or N-(4-aminobenzoyl)-β-alanine [3-(4-
aminophenylcarboxamido)propanoic acid] fragment.
The alkylation of 2-, 3-, and 4-aminobenzoic acids,
ethyl 4-aminobenzoate (benzocaine), 2-diethylamino-
General procedure for the synthesis of com-
pounds 2–9. A mixture of 1.37 g (0.01 mol) of the cor-
responding aminobenzoic acid and 0.01 mol of amino
ketone 1 in 20 mL of water was heated for 1.5–2 h on a
boiling water bath. The mixture was cooled, and the
precipitate was filtered off and washed on a filter with
342

343
SYNTHESIS OF β-AMINO KETONES DERIVED FROM AMINOBENZOIC ACIDS
Scheme 1.
COOH
COOH
O
H2N
N
H
R1
2−9
O
COOR2
COOR2
NEt2
HCl
O
H2N
R1
N
H
1
R1
O
O
10−17
O
O
H2N
O
N
OH
H
HN
OH
N
H
R1
18−21
2-COOH, R1 = H (2); 3-COOH, R1 = H, (3), 4-Cl (4), 4-EtO (5), 4-i-PrO (6); 4-COOH, R1 = H (7), 4-EtO (8), 4-PrO (9);
R1 = H, R2 = Et (10); R1 = 4-Cl, R2 = Et (11); R1 = 4-MeO, R2 = Et (12); R1 = 4-i-PrO, R2 = Et (13); R1 = H, R2 =
Et2NCH2CH2 (14); R1 = 4-HO, R2 = Et2NCH2CH2 (15); R1 = 4-Me, R2 = Et2NCH2CH2 (16); R1 = 4-MeO, R2 =
Et2NCH2CH2 (17); R1 = H (18), 4-Cl (19), 4-EtO (20), 4-i-PrO (21).
cold water and ethanol. An additional amount of the
product was isolated by evaporation of the mother
liquor by half. The product was purified by
recrystallization from ethanol or aqueous ethanol
(1 : 1).
7.97 m (2H, o-H). Found, %: C 71.64; H 5.35; N 5.36.
C16H15NO3. Calculated, %: C 71.36; H 5.61; N 5.20.
3-[3-(4-Chlorophenyl)-3-oxopropylamino)]benzoic
acid (4). Yield 83%, mp 168–170°C, Rf 0.66. IR spec-
trum, ν, cm–1: 3383 (NH), 1695 (COOH), 1670 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 3.28 t (2H, CH2,
J = 6.6), 3.50 t (2H, NCH2, J = 6.6), 3.87 br.s (1H,
NH), 6.76–6.81 m (1H, 6-H), 7.13 d.d (1H, 5-H, J =
8.0, 7.5), 7.18–7.24 m (2H, 2-H, 4-H), 7.43–7.48 m
(2H, 3′-H, 5′-H), 7.93–7.98 m (2H, 2′-H, 6′-H), 11.95
br.s (1H, COOH). Found, %: C 63.50; H 4.31; Cl
11.40; N 4.35. C16H14ClNO3. Calculated, %: C 63.27;
H 4.65; Cl 11.67; N 4.61.
2-(3-Oxo-3-phenylpropylamino)benzoic acid (2).
Yield 58%, mp 145–147°C, Rf 0.67. IR spectrum, ν,
1
cm–1: 3370 (NH), 1675 (C=O). H NMR spectrum, δ,
ppm (J, Hz): 3.34 t (2H, CH2, J = 6.7), 3.63 t (2H,
NCH2, J = 6.7), 6.50 d.d.d (1H, 5-H, J = 8.0, 7.1, 1.0),
6.72 d.d (1H, 3-H, J = 8.4, 1.0), 7.29 d.d.d (1H, 4-H,
J = 8.4, 7.1, 1.7), 7.43–7.49 m (2H, m-H), 7.53–7.59 m
(1H, p-H), 7.81 d.d (1H, 6-H, J = 8.0, 1.7), 7.95–8.00 m
(2H, o-H), 7.98 br.s (1H, NH), 12.04 br.s (1H, COOH).
Found, %: C 71.52; H 5.31; N 4.95. C16H15NO3.
Calculated, %: C 71.36; H 5.61; N 5.20.
3-[3-(4-Ethoxyphenyl)-3-oxopropylamino)]benzoic
acid (5). Yield 93%, mp 165–168°C, Rf 0.67. IR spec-
1
trum, ν, cm–1: 3407 (NH), 1669 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 1.42 t (3H, CH3, J = 7.0),
3.20 t (2H, CH2, J = 6.6), 3.48 t (2H, NCH2, J = 6.6),
4.09 q (2H, OCH2, J = 7.0), 5.17 br.s (1H, NH), 6.74–
6.79 m (1H, 6-H), 6.86–6.92 m (2H, 3′-H, 5′-H), 7.12 t
(1H, 5-H, J = 7.7), 7.16–7.23 m (2H, 2-H, 4-H), 7.87–
93 m (2H, 2′-H, 6′-H), 12.00 br.s (1H, COOH). Found,
%: C 69.25; H 6.30; N 4.25. C18H19NO4. Calculated,
%: C 69.00; H 6.11; N 4.47.
3-(3-Oxo-3-phenylpropylamino)benzoic acid (3).
Yield 42%, mp 170–171°C, Rf 0.67. IR spectrum, ν,
1
cm–1: 1764 (COOH), 1680 (C=O). H NMR spectrum,
δ, ppm (J, Hz): 3.30 t (2H, CH2, J = 6.6), 3.51 t (2H,
NCH2, J = 6.6), 3.52 br.s (1H, NH), 6.81 m (1H, 6-H),
7.14 t (1H, 5-H, J = 7.7), 7.19–7.26 m (2H, 2-H, 4-H),
7.43–7.50 m (2H, m-H), 7.52–7.58 m (1H, p-H), 7.92–
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GEVORGYAN et al.
3-{3-Oxo-3-[4-(propan-2-yloxy)phenyl]propyl-
(1H, NH), 4.22 q (2H, OCH2, J = 7.1), 6.54–6.59 m
(2H, 2-H, 6-H), 7.44–7.50 m (2H, m-H), 7.53–7.60 m
(1H, p-H), 7.67–7.72 m (2H, 3-H, 5-H), 7.93–7.98 m
(2H, o-H). Found, %: C 72.84; H 6.13; N 4.85.
C18H19NO3. Calculated, %: C 72.71; H 6.44; N 4.71.
amino}benzoic acid (6). Yield 57%, mp 161–162°C,
Rf 0.68. IR spectrum, ν, cm–1: 3363 (NH), 1694 (COOH),
1
1670 (C=O). H NMR spectrum, δ, ppm (J, Hz): 1.34
d (6H, CH3, J = 6.1), 3.20 t (2H, CH2, J = 6.6), 3.46 t
(2H, NCH2, J = 6.6), 4.68 sept (1H, CH, J = 6.1), 5.45
br.s (1H, NH), 6,75 d.d.d (1H, 6-H, J = 7.6, 2.3, 1.4),
6.86–6.91 m (2H, 3′-H, 5′-H), 7.09–7.20 m (3H, 2-H,
4-H, 5-H), 7.87–7.92 m (2H, 2′-H, 6′-H), 12.07 br.s
(1H, COOH). Found, %: C 69.50; H 6.58; N 4.50.
C19H21NO4. Calculated, %: C 69.71; H 6.47; N 4.28.
Ethyl-4-[3-(4-chlorophenyl)-3-oxopropylamino]-
benzoate (11). Yield 98%, mp 207–208°C, Rf 0.67. IR
spectrum, ν, cm–1: 3367 (NH), 1694 (COOEt), 1680
(C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.34 t (3H,
CH3, J = 7.1), 3.28 t (2H, CH2, J = 6.6), 3.51 t (2H,
NCH2, J = 6.6), 4.22 q (2H, OCH2, J = 7.1), 6.16 br.s
(1H, NH), 6.52–6.57 m (2H, 2-H, 6-H), 7.45–7.50 m
(2H, 3′-H, 5′-H), 7.67–7.72 m (2H, 3-H, 5-H), 7.92–
7.97 m (2H, 2′-H, 6′-H). Found, %: C 65.37; H 5.50;
Cl 10.42; N 4.10. C18H18ClNO3. Calculated, %: C
65.16; H 5.47; Cl 10.68; N 4.22.
4-(3-Oxo-3-phenylpropylamino)benzoic acid (7).
Yield 59%, mp 145–147°C, Rf 0.67. IR spectrum, ν,
1
cm–1: 3350 (NH), 1680 (C=O). H NMR spectrum, δ,
ppm (J, Hz): 3.60 t (2H, CH2, J = 5.5), 3.95 t (2H,
NCH2, J = 5.5), 7.51–7.58 m (2H, C6H5), 7.67–7.75 m
(3H, C6H5), 7.94–7.99 m (2H, C6H4), 8.27–8.33 m
(2H, C6H4). Found, %: C 71.91; H 5.40; N 5.30.
C16H15NO3. Calculated, %: C 71.36; H 5.61; N 5.20.
Ethyl 4-[3-(4-methoxyphenyl)-3-oxopropylamino]-
benzoate (12). Yield 88%, mp 243–245°C, Rf 0.70. IR
spectrum, ν, cm–1: 3387 (NH), 1694 (COOEt), 1680
(C=O). 1H NMR spectrum, δ, ppm (J, Hz): 1.34 t (3H,
CH3, J = 7.1), 3.22 t (2H, CH2, J = 6.6), 3.50 t (2H,
NCH2, J = 6.6), 3.87 s (3H, OCH3), 4.22 q (2H, OCH2,
J = 7.1), 6.13 br.s (1H, NH), 6.52–6.57 m (2H, 2-H, 6-
H), 6.91–6.96 m (2H, 3′-H, 5′-H), 7.66–7.71 m (2H, 3-
H, 5-H), 7.90–7.95 m (2H, 2′-H, 6′-H). Found, %: C
69.55; H 6.26; N 4.55. C19H21NO4. Calculated, %: C
69.71; H 6.47; N 4.28.
4-[3-(4-Ethoxyphenyl)-3-oxopropylamino]benzoic
acid (8). Yield 59%, mp 145–147°C, Rf 0.72. IR spec-
trum, ν, cm–1: 3350 (NH), 1680 (C=O). 1H NMR spec-
trum, δ, ppm (J, Hz): 1.35 t (3H, CH3, J = 6.9), 3.25 t
(2H, CH2, J = 6.6), 3.44 t.d (2H, NCH2, J = 6.6, 5.5),
4.12 q (2H, OCH2, J = 6.9), 6.42 t (1H, NH, J = 5.5),
6.56–6.61 m (2H, 2-H, 6-H), 6.99–7.05 m (2H, 3′-H,
5′-H), 7.64–7.69 m (2H, 2′-H, 6′-H), 7.90–7.95 m (2H,
3-H, 5-H), 11.95 br.s (1H, COOH). Found, %: C 69.29;
H 6.30; N 4.60. C18H19NO4. Calculated, %: C 69.00; H
6.11; N 4.47.
Ethyl 4-{3-oxo-3-[4-(propan-2-yloxy)phenyl]propyl-
amino}benzoate (13). Yield 68%, mp 155–156°C, Rf
0.71. IR spectrum, ν, cm–1: 3391, 3363 (NH), 1698
1
(COOEt), 1675 (C=O). H NMR spectrum, δ, ppm
4-{3-Oxo-3-[4-(propan-2-yloxy)phenyl]propyl-
amino}benzoic acid (9). Yield 80%, mp 229–231°C,
Rf 0.67. IR spectrum, ν, cm–1: 3360 (NH), 1665 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.06 t (3H, CH3,
J = 7.4), 1.82 t (2H, CH3CH2), 3.21 t (2H, CH2CH2N,
J = 6.6), 3.49 t. d (2H, NHCH2, J = 6.6, 5.7), 3.99 t
(2H, OCH2, J = 6.5), 5.96 s (1H, NH), 6.04 t (1H, NH,
J = 5.7), 6.55 m (2H, 2-H, 6-H), 6.91 m (2H, 3′-H, 5′-H),
7.68 m (2H, 3-H, 5-H), 7.90 m (2H, 2′-H, 6′-H), 11.51
br.s (1H, COOH). Found, %: C 69.47; H 6.58; N 4.14.
C19H21NO4. Calculated, %: C 69.71; H 6.47; N 4.28.
(J, Hz): 1.34 t (3H, CH3CH2O, J = 7.0), 1.35 d (6H,
CH3, J = 6.0), 3.21 t (2H, CH2, J = 6.6), 3.50 t (2H,
NCH2, J = 6.6), 4.22 q (2H, OCH2, J = 7.0), 4.68 sept
(1H, OCH, J = 6.0), 6.12 br.s (1H, NH), 6.52–6.57 m
(2H, 2-H, 6-H), 6.86–6.91 m (2H, 3′-H, 5′-H), 7.66–
7.71 m (2H, 3-H, 5-H), 7.86–7.91 m (2H, 2′-H, 6′-H).
Found, %: C 70.75; H 7.26; N 4.11. C21H25NO4.
Calculated, %: C 70.96; H 7.09; N 3.94.
2-(Diethylamino)ethyl 4-(3-oxo-3-phenylpropyl-
amino)benzoate (14). Yield 67%, mp 201–204°C, Rf
0.67. IR spectrum, ν, cm–1: 3372 (NH), 1676 (C=O).
1H NMR spectrum, δ, ppm (J, Hz): 1.04 t (6H, CH3,
J = 7.1), 2.56 q (4H, NCH2CH3, J = 7.1), 2.73 t (2H,
NCH2CH2O, J = 6.3), 3.29 t [2H, C(O)CH2, J = 6.6],
3.52 t. d (2H, NHCH2, J = 6.6, 5.7), 4.19 t (2H, OCH2,
J = 6.4), 6.17 br.t (1H, NH, J = 5.7), 6.53–6.58 m (2H,
2-H, 6-H), 7.44–7.50 m (2H, m-H), 7.53–7.59 m (1H,
p-H), 7.66–7.71 m (2H, 3-H, 5-H), 7.94–7.98 m (2H,
Compounds 10–17 were synthesized in a similar
way from benzocaine or novocaine.
Ethyl 4-(3-oxo-3-phenylpropylamino)benzoate (10).
Yield 34%, mp 163–164°C, Rf 0.67. IR spectrum, ν,
1
cm–1: 3379 (NH), 1677 (C=O). H NMR spectrum, δ,
ppm (J, Hz): 1.34 t (3H, CH3, J = 7.1), 3.29 t (2H,
CH2, J = 6.6), 3.53 t (2H, NCH2, J = 6.6), 3.74 br.s
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SYNTHESIS OF β-AMINO KETONES DERIVED FROM AMINOBENZOIC ACIDS
o-H). Found, %: C 71.85; H 7.90; N 7.40. C22H28N2O3.
Calculated, %: C 71.71; H 7.66; N 7.60.
(2H), 7.53–7.59 m (1H), and 7.94–7.98 m (2H) (C6H5);
7.77 br.t (1H, CONH, J = 5.7), 11.8 br.s (1H, COOH);
the NH signal is strongly broadened due to exchange
with water present in the solvent and is observed at
δ ~5.8 ppm. Found, %: C 67.24; H 6.26; N 8.05.
C19H20N2O4. Calculated, %: C 67.05; H 5.92; N 8.23.
2-Diethylaminoethyl 4-[3(4-hydroxyphenyl)-3-oxo-
propylamino]benzoate hydrochloride (15). Yield
69%, mp 211–213°C, Rf 0.65. IR spectrum, ν, cm–1:
1
3354 (NH), 1662 (C=O). H NMR spectrum, δ, ppm
(J, Hz): 1.37 t (6H, CH3, J = 7.2), 3.13–3.26 m [6H,
NCH2CH2, C(O)CH2], 3.40–3.53 m (4H, NCH2), 4.63
br.t (2H, OCH2, J = 5.0), 6.35 br.s (1H, NH), 6.55–6.60
m and 6.78–6.83 m (2H each, C6H4N), 7.71–7.82 m
(4H, C6H4O), 9.97 br.s (1H, OH), 12.06 br.s (1H, HCl).
Found, %: N 6.52; Cl 8.50. C22H28N2O4 · HCl.
Calculated, %: N 6.67; Cl 8.42.
3-{4-[3-(4-Chlorophenyl)-3-oxopropylamino]-
benzamido}propanoic acid (19). Yield 36%, mp 199–
200°C, Rf 0.67. IR spectrum, ν, cm–1: 3368 (NHAr),
1
3349 (NHamide), 1734 (COOH), 1670 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 2.48 t (2H, CH2COOH, J =
7.0), 3.28 t [2H, C(O)CH2, J = 6.6], 3.42–3.53 m [4H,
NHCH2CH2COOH, C(O)CH2CH2], 6.56–6.61 m and
7.57–7.62 m (2H each, C6H4N), 7.43–7.48 m and 7.93–
7.98 m (2H each, C6H4Cl), 7.73 br.t (1H, CONH, J =
5.7), 11.9 br.s (1H, COOH); the NH signal is strongly
broadened due to exchange with water present in the
solvent and is observed at δ ~4.4 ppm. Found, %: C
60.64; H 5.26; Cl 9.85; N 7.75. C19H19ClN2O4.
Calculated, %: C 60.88; H 5.11; Cl 9.46; N 7.47.
2-Diethylaminoethyl 4-[3(4-methylphenyl)-3-oxo-
propylamino]benzoate hydrochloride (16). Yield
65%, mp 174–175°C, Rf 0.68. IR spectrum, ν, cm–1:
1
3373 (NH), 1674 (C=O). H NMR spectrum, δ, ppm
(J, Hz): 1.37 t (6H, CH3, J = 7.2), 2.42 s (3H,
CH3C6H4), 3.16–3.26 m [4H, N(CH2CH3)2], 3.26 t
[2H, C(O)CH2, J = 6.5], 3.40–3.46 m (2H, NCH2),
3.52 t (2H, CH2NH, J = 6.5), 4.61–4.66 m (2H,
OCH2), 6.56–6.62 m (2H, C6H4N), 7.24–7.29 m and
7.71–7.76 m (2H each, CH3C6H4), 7.82–7.87 m (2H,
C6H4N), 12.17 br.s (2H, NH, HCl). Found, %: N 6.73;
Cl 8.51. C23H30N2O3·HCl. Calculated, %: N 6.70; Cl 8.46.
3-{4-[3-(4-Ethoxyphenyl)-3-oxopropylamino]-
benzamido}propanoic acid (20). Yield 79%, mp 212–
214°C, Rf 0.69. IR spectrum, ν, cm–1: 3380 (NHAr),
1
3340–3320 (NHamide), 1715 (COOH), 1670 (C=O). H
NMR spectrum, δ, ppm (J, Hz): 1.43 t (3H, CH3, J =
7.0), 2.48 t (2H, CH2COOH, J = 6.9), 3.22 t [2H, C(O)
CH2, J = 6.6], 3.43–3.51 m [4H, C(O)CH2CH2,
NHCH2CH2COOH), 4.10 q (2H, OCH2CH3, J = 7.0),
4.6 br.s (1H, NHC6H4), 6.56–6.63 m and 7.57–7.62 m
(2H each, C6H4N), 6.87–6.92 m and 7.88–7.93 m (2H
each, C6H4O), 7.73 t (1H, CONH, J = 5.5), 11.8 br.s
(1H, COOH); the NH signal is strongly broadened due
to exchange with water present in the solvent and is
observed at δ ~4.6 ppm. Found, %: C 65.74; H 6.06; N
7.06. C21H24N2O5. Calculated, %: C 65.61; H 6.29; N
7.29.
2-Diethylaminoethyl 4-[3-(4-methoxyphenyl)-3-oxo-
propylamino]benzoate hydrochloride (17). Yield
70%, mp 144–146°C, Rf 0.67. IR spectrum, ν, cm–1:
1
3384 (NH), 1707.7 (COO), 1660 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 1.37 t (6H, CH3, J = 7.1),
3.17–3.26 m (6H, CH2N), 3.41–3.45 br.q (2H, NHCH2,
J = 5.1), 3.51 t [2H, C(O)CH2, J = 6.6], 3.87 s (3H,
OCH3), 4.63 t (2H, OCH2, J = 5.1), 6.28 br.s (1H, NH),
6.56–6.61 m (2H, 2-H, 6-H), 6.92–6.97 m (2H,
C6H4O), 7.71–7.76 m (2H, 3-H, 5-H), 7.89–7.94 m
(2H, C6H4O), 6.28 br.s (1H, NH), 12.16 br.s (1H, HCl).
Found, %: N 6.31; Cl 8.09. C23H30N2O4·HCl. Cal-
culated, %: N 6.45; Cl 8.16.
3-{4-[3-Oxo-3-(4-propan-2-yloxy)propylamino]-
benzamido}propanoic acid (21). Yield 68%, mp 213–
214°C, Rf 0.66. IR spectrum, ν, cm–1: 3390 (NHAr),
3350 (NHam1ide), 1720 (COOH), 1685 (C=O), 1650
(C=Oamide). H NMR spectrum, δ, ppm (J, Hz): 1.35 d
(6H, CH3, J = 6.0), 2.48 t (2H, CH2COOH, J = 6.9),
3.20 t [2H, C(O)CH2, J = 6.6], 3.42–3.51 m [4H, C(O)
CH2CH2, NHCH2CH2COOH], 4.68 sept [1H, OCH(CH3)2,
J = 6.0], 5.5 br.s (1H, NHC6H4), 6.53–6.58 m and 7.56–
7.61 m (2H each, C6H4N), 6.87–6.92 m and 7.86–7.91
m (2H each, C6H4O), 7.75 t (1H, CONH, J = 5.5), 11.8
br.s (1H, COOH). Found, %: C 66.21; H 6.77; N 6.89.
C22H26N2O5. Calculated, %: C 66.32; H 6.58; N 7.03.
Compounds 18–21 were synthesized in a similar
way from N-(4-aminobenzoyl)-β-alanine.
3-[4-(3-Oxo-3-phenylpropylamino)benzamido]-
propanoic acid (18). Yield 87%, mp 111–113°C, Rf
0.65. IR spectrum, ν, cm–1: 3380 (NHAr), 3352 (NHamide),
1
1692 (COOH), 1675 (C=O). H NMR spectrum, δ,
ppm (J, Hz): 2.48 t (2H, CH2COOH, J = 7.0), 3.29 t
[2H, C(O)CH2, J = 6.7], 3.42–3.49 m (2H, NHCH2CH2·
COOH), 3.50 t [2H, C(O)CH2CH2, J = 6.7], 6.54–6.59
m and 7.57–7.62 m (2H each, C6H4); 7.44–7.50 m
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 87 No. 2 2017

346
GEVORGYAN et al.
2. Gal’binur, T.P., Mol. Med., 2012, no. 5, p. 11.
The IR spectra were recorded on a NEXUS FT-IR
spectrometer. The H NMR spectra were measured on
1
3. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
a Varian Mercury 300 spectrometer at 300 MHz using
DMSO–d6–CCl4 (1 : 3) as solvent and tetramethyl-
silane as internal standard. Analytical thin-layer chro-
matography was performed on Silufol UV-254 plates
(eluent butan-1-ol–ethanol–acetic acid–water 8 : 2 : 1 : 3;
development with iodine vapor). The melting points
were determined on a Boetius melting point apparatus.
Moscow: Novaya Volna, 2010, 16th ed.
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ratus (Analytic Jena, Germany) using a commercial
ACL kit for the determination of integral activity of
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to Trolox (water-soluble analog of vitamin E) as
standard drug and was expressed in units equivalent to
the amount of the standard in nanomoles showing the
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6. Shakirova, A.B., Cand. Sci. (Pharm.) Dissertation,
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7. Agababyan, A.G., Gevorgyan, G.A., Avakyan, A.P.,
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