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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 5, May, 2009
Volod´kin et al.
1
data,1 m.p. 203 °C. Н NMR (acetoneꢀd6), δ: 1.42 (s, 18 Н,
But); 1.96 (s, 3 H, CОCН3); 2.94 (dd, 1 Hа, J = 7.6 Hz); 3.11
(dd, 1 Hb, J = 5.0 Hz); 4.63—4.69 (m, 1 НC); 5.90 (s, 1 H, OH);
that the difference is 41.796 kJ mol–1 (9.98 kcal mol–1).
In the nonpolar solvent (cumene) structure 3с (B) is more
stable, because the dipole moment (D) of structure 3c (В)
is 3.47 D, which is lower than D 3c (A) = 6.13 D.
The data in Table 1 show that compounds 2d, 3b, and
3с are insufficiently efficient antioxidants, whereas comꢀ
pounds 3а and 4 can be interest as waterꢀsoluble and
efficient antioxidants.
7.05 (s, 2 H, Ar); 7.45 (d, 1 H, NH, J = 5.0 Hz). IR, ν/cm–1
:
3639 (ОН); 3332 (NHCОCН3); 2954, 2913, 2872 (CH); 1715
(COОН); 1624 (HNCO); 1550 (C=C), 1433, 1269, 1218, 1188,
1157, 1120. Found (%): C, 67.84; H, 8.85; N, 4.16. C19H29NO4.
Calculated (%): C, 68.03; H, 8.72; N, 4.18.
Ethyl hydrogen Nꢀacetylamino(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxyꢀ
benzyl)malonate (2c). A mixture of compound 1 (43.6 g, 0.1 mol)
and AcONa (8.2 g, 0.1 mol) in water (30 mL) and propanꢀ2ꢀol
(200 mL) was stored for 3 days at room temperature, after which
10% HCl (35 mL) was added. Compound 2c was obtained in a
yield of 26.1 g (64%), m.p. 175—176 °C (from toluene).
1Н NMR (DMSOꢀd6), δ: 1.24 (t, 3 Н, CН2CН3, J = 7.1 Hz);
1.34 (s, 18 Н, But); 1.89 (s, 3 H, COCH3); 3.22 (s, 2 H, CН2);
4.13 (2 Н, CН3CН2, J = 7.1 Hz); 6.34 (s, 1 H, OH); 6.76 (s,
2 H, Ar); 7.39 (s, 1 H, NH). IR, ν/cm–1: 3633 (ОН); 3345
(NHCОCН3); 2954 (CH); 1749 (CООC2Н5); 1714 (COОН);
1619 (HNCОCН3); 1533 (C=C); 1435, 1235, 1212, 1149.
Found (%): C, 64.89; H, 8.33; N, 3.31. C22H33NO6. Calcuꢀ
lated (%): C, 64.85; H, 8.16; N, 3.44.
Ethyl 2ꢀ(Nꢀacetylamino)ꢀ3ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxyꢀ
phenyl)propanoate (3c) is formed on heating monoethyl ester 2c
to temperatures higher than 176 °C due to decarboxylation.
M.p. 135—136 °C (from toluene). 1Н NMR (acetoneꢀd6), δ:
1.68 (t, 3 Н, CН3CН2, J = 7.1 Hz); 1.42 (s, 18 Н, But); 1.91
(s, 3 H, COCH3); 2.02 (dd, 1 Hа, J = 6.2 Hz); 3.11 (dd, 1 Hb,
J = 6.3 Hz); 4.09 (2 Н, CН3CН2, J = 7.1 Hz); 4.60—4.64 (m,
1 НC); 5.98 (s, 1 H, OH); 6.95 (s, 2 H, Ar); 7.34 (d, 1 H, NH,
J = 7.15 Hz). IR, ν/cm–1: 3354 (NHCОCН3); 3189 br (OH);
2948 (CH); 1732 (COOC2Н5); 1647 (HNCO); 1548 (C=C);
1435; 1253; 1211; 1039. Found (%): C, 69.59; H, 9.13; N, 3.94;
C21H33NO4. Calculated (%): C, 69.40; H, 9.15; N, 3.85.
NꢀAcetylamino(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxybenzyl)malonate
(2d). A solution of compound 2a (4.2 g, 0.01 mol) in water
(50 mL) was treated with 10% HCl (5 mL). The precipitate
formed was separated, dried at 25—30 °C, and crystallized from
a toluene—EtOH (9 : 1, vol.) mixture. The yield was 92—96%,
m.p. 198—200 °C (from toluene). According to the literature
data,1 m.p. 148 °C. 1Н NMR (DMSOꢀd6), δ: 1.34 (s, 18 Н,
But); 1.87 (s, 3 H, COCH3); 3.22 (s, 2 H, CН2); 6.74 (s, 2 H, Ar);
7.69 (s, 1 H, NH). IR, ν/cm–1: 3637 (ОН); 3338 (NHCОCН3);
2954, 2913, 2872 (CH), 1716 (COOН); 1623 (HNCОCН3);
1536 (C=C), 1435, 1214, 1155, 1121. Found (%): C, 63.24; H,
7.95; N, 3.86. C20H29NO6. Calculated (%): C, 63.31; H, 7.70;
N, 3.69.
Experimental
The parameters of the structures of the synthesized comꢀ
pounds were calculated using the Mopacꢀ2007, Version 8.288W
program in the РМ6 approximation. 1Н NMR spectra were
recorded on a Bruker WMꢀ400 instrument (400 MHz) relative
to the signal of residual protons of the deuterated solvent
(acetoneꢀd6 or DMSOꢀd6). IR diffuse reflectance spectra were
recorded on a PerkinꢀElmer 1725ꢀX spectrometer for crystals.
The antioxidation parameters of the synthesized compounds
were determined by a known method9 under the conditions of
inhibited oxidation of cumene with oxygen at 50 °C in the
presence of the oxidation initiator (azodiisobutyronitrile).
Diethyl Nꢀacetylamino(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxybenzyl)ꢀ
malonate (1) was synthesized by a known procedure,6 m.p. 130 °C.
1Н NMR (acetoneꢀd6), δ: 1.25 (t, 6 Н, CН2CН3, J = 7.1 Hz);
1.40 (s, 18 Н, But); 2.07 (s, 3 H, COCH3); 2.89 (s, 1 H, CH2);
4.20—4.23 (m, 4 Н, CH2CH3); 6.01 (s, 1 H, OH); 6.82 (s, 2 H,
Ar); 7.29 (br.s, 1 H, NH).
Alkaline hydrolysis of compound 1. Compound 1 (4.36 g,
0.01 mol) was added to a solution of NaOH (0.84 g, 0.06 mol) in
dioxane (25 mL) and water (3 mL) at 100 °C in an argon flow,
and samples for analysis were taken at an interval of 30 min for
3 h under the temperatureꢀcontrolled conditions. The comꢀ
position of the reaction mixtures was monitored (after neutralꢀ
ization to pH 4) using the comparison of the 1Н NMR spectra in
an acetoneꢀd6 solution by the signals from metaꢀprotons of the
aromatic ring of the initial ester 1 (δ 6.820) and reaction
Н
products: δН 7.05 (3b), δН 6.95 (3c), and δН 6.92 (2d).
Synthesis of monosodium salt of Nꢀacetylamino(3,5ꢀdiꢀtertꢀ
butylꢀ4ꢀhydroxybenzyl)malonic acid (2a) and 2ꢀ(Nꢀacetylamino)ꢀ
3ꢀ(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxyphenyl)propanoic acid (3b).
A mixture of compound 1 (43.6 g, 0.1 mol), NaOH (4 g,
0.1 mol), water (20 mL), and dioxane (200 mL) was heated for
2 h at 85—90 °C in an argon flow. Then the reaction mixture
was cooled down, and the precipitate formed was separated and
recrystallized from aqueous ethanol (8 : 2). Crystalline hydrate
of salt 2a was obtained in a yield of 23.4 g (62%), m.p. 258—260 °C
NꢀAcetylamino(3,5ꢀdiꢀtertꢀbutylꢀ4ꢀhydroxybenzyl)malonic
acid diammonium salt (2e). Ammonia (2.2 mL, 0.1 mol) was
added to a solution of acid 2d (3.37 g, 0.01 mol) in EtOH (15 mL).
The reaction mixture was stirred for 30 min, and ammonia and
solvent excess were distilled off. Water (10 mL) was added to the
residue, and the mixture was heated and filtered. The filtrate
was cooled to 5—6 °C and stored until precipitation, and the
precipitate was separated by filtration. Compound 2e was
obtained in a yield of 3.1 g (83%), m.p. 177—178 °C (from
1
(with decomp.). Н NMR (DMSOꢀd6), δ: 1.26 (s, 18 Н, But);
1.79 (s, 3 Н, CОCН3); 3.37 (s, 2 Н, CН2); 3.40—3.48 (br.s,
НОН); 6.42—6.46 (br.s, 1 H, OH); 6.79 (s, 2 H, Ar); 7.20—7.27
(br.s, 1 H, NH). IR, ν/cm–1: 3643 (ОН); 3550—3100 br (НОH);
3321 (NHCОCН3); 2957 (CH); 1550—1615 br (HNCО, CОО–,
C=C); 1507; 1433; 1417; 1287; 1234; 1215; 1156; 1123. Found (%):
C, 56.96; H, 7.37; N, 3.52; Na, 5.55. C20H28NO6Na•H2O.
Calculated (%): C, 57.27; H, 7.20; N, 3.34; Na, 5.48.
EtOH). Н NMR (DMSOꢀd6), δ: 1.29 (s, 18 Н, But); 1.75 (s,
1
The mother liquor was treated with 10% HCl to pH 4, the
solvent was evaporated, and the residue was crystallized from
acetone. Compound 3b was obtained in a yield of 5.37 g (17%),
m.p. 205—206 °C (from EtOH). According to the literature
3 H, COCH3); 2.52 (s, 2 H, CН2); 3.85—4.01 (br.s,. 8 H, NH4);
6.80 (s, 2 H, Ar); 7.04—7.06 (br.s, 1 H, NH). Found (%):
C, 57.95; H, 8.71; N, 10.26. C20H35N3O6. Calculated (%):
C, 58.01; H, 8.53; N, 10.16.