Azomethines on the basis of sodium salts of valine and leucine

Article abstract of DOI:10.1023/B:RUGC.0000015996.53534.48

Sodium salts of valine and leucine [RCH(NH₂)COONa, R = (CH ₃)₂CH, (CH₃)₂CHCH₂] were reacted with benzaldehyde and its derivatives to obtain azomethines RCH(COONa)N=CHAr (Ar = C₆H

Full text of DOI:10.1023/B:RUGC.0000015996.53534.48

Russian Journal of General Chemistry, Vol. 73, No. 9, 2003, pp. 1445 1447. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 9, 2003,
pp. 1529 1531.
Original Russian Text Copyright
2003 by Knizhnikov, Azizbekyan, Prishchepenko.
Azomethines on the Basis of Sodium Salts of Valine and Leucine
V. A. Knizhnikov, O. P. Azizbekyan, and V. M. Prishchepenko
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus
Received October 18, 2001
Abstract Sodium salts of valine and leucine [RCH(NH2)COONa, R = (CH3)2CH, (CH3)2CHCH2] were
reacted with benzaldehyde and its derivatives to obtain azomethines RCH(COONa)N=CHAr (Ar = C6H5,
1
2-ClC6H4, 4-ClC6H4, 2-HOC6H4, 4-HOC6H4). The structure of the products was proved by IR and H NMR
spectroscopy, mass spectrometry, and elemental analysis.
Amino acids and their derivatives exhibit a well-
pronounced physiological activity and enter in the
composition of a series of medicinal drugs and bio-
stimulants [1 3]. Therefore, we considered it topical
to synthesize novel organic derivatives of amino acids
and to study their biological activity. Schiff bases are
widely used in organic synthesis [4, 5]. However,
azomethines derived from amino acids and their syn-
thetic applications have poorly been explored. In the
present work we report on the synthesis of azo-
methines on the basis of sodium salts of valine and
leucine.
leucine in absolute methanol of benzaldehyde or its
derivatives.
O
NH2
N=CH Ar
Ar C H
R CH C ONa
O
R CH
C ONa
O
II XI
Ia, Ib
R = (CH3)2CH (Ia); Ar = C6H5 (II), 2-ClC6H4 (III),
4-ClC6H4 (IV), 2-HOC6H4 (V), 4-HOC6H4 (VI); R =
(CH3)2CHCH2 (Ib); Ar = C6H5 (VII), 2-ClC6H4 (VIII),
4-ClC6H4 (IX), 2-HOC6H4 (X), 4-HOC6H4 (XI).
It was found that both valine and leucine fail to
react with benzaldehyde in absolute methanol at room
temperature. Stirring of the reaction mixtures for 5
days, too, gave no Schiff bases. At the same time,
azomethines readily formed in mild conditions
on addition to solutions of sodium salts of valine or
The synthesized compounds are solids soluble in
methanol, ethanol, and water and poorly soluble in
ordinary organic solvents. Their physicochemical
characteristics are listed in Table 1.
Table 1. Physicochemical and spectral characteristics of Schiff bases
IR spectrum,
,
Found, %
H
Calculated, %
H
1
Comp. Yield,
mp,
C
cm
Formula
no.
%
C=O
C=N
C
N
C
N
II
89
91
90
85
83
90
90
92
87
84
278 280
260 262
268 270
1597
1592
1596
1604
1577
1592
1592
1594
1609
1581
1642
1633
1639
1635
1642
1642
1633
1643
1636
1643
63.69
55.24
55.27
59.50
59.43
65.01
56.98
56.81
60.87
60.75
6.41
5.28
5.31
6.01
6.07
6.93
5.71
5.52
6.38
6.44
5.93 C12H14NNaO2
5.14 C12H13ClNNaO2 55.08
5.06 C12H13ClNNaO2 55.08
5.55 C12H14NNaO3
5.48 C12H14NNaO3
5.66 C13H16NNaO2
4.87 C13H15ClNNaO2 56.63
4.76 C13H15ClNNaO2 56.63
63.43
6.21
5.01
5.01
5.80
5.80
6.68
5.48
5.48
6.29
6.29
6.16
5.35
5.35
5.76
5.76
5.81
5.08
5.08
5.45
5.45
III
IV
V
VI
VII
VIII
IX
X
230 233
59.26
59.26
64.72
a
276 278
253 255
264 266
166 168
5.31 C13H16NNaO3
5.52 C13H16NNaO3
60.69
60.69
a
XI
a
Decomposes.
1070-3632/03/7309-1445$25.00 2003 MAIK Nauka/Interperiodica

1446
KNIZHNIKOV et al.
Table 2. 1H NMR spectra of valine derivatives, , ppm
Comp.
no.
CH3
(CH3)2CH
NaOOCCH
ArCH
Ar
Ia 0.85 d (3H, J 7 Hz), 1.92 2.03 m (1H) 3.04 d (1H, J 4.8 Hz)
0.96 d (3H, J 7 Hz)
II
0.88 d (3H, J 6.7 Hz), 2.11 2.49 m (1H) 3.46 d (1H, J 8 Hz)
0.99 d (3H, J 6.7 Hz)
8.26 s (1H) 7.37 7.44 m (3H),
7.75 7.84 m (2H)
III 0.89 d (3H, J 6.8 Hz), 2.15 2.50 m (1H) 3.53 d (1H, J 7.6 Hz) 8.65 s (1H) 7.27 7.41 m (3H),
0.99 d (3H, J 6.7 Hz) 8.03 8.13 m (1H)
IV 0.87 d (3H, J 6.7 Hz), 2.11 2.50 m (1H) 3.47 d (1H, J 7.7 Hz) 8.23 s (1H) 7.40 d (2H, J 8.4 Hz),
1.03 d (3H, J 6.4 Hz) 7.79 d (2H, J 8.5 Hz)
0.97 d (3H, J 6.7 Hz), 2.12 2.50 m (1H) 3.69 d (1H, J 5.9 Hz) 8.31 s (1H) 6.69 6.83 m (2H),
0.99 d (3H, J 6.9 Hz) 7.21 7.35 m (2H)
VI 0.89 d (3H, J 6.7 Hz), 2.14 2.48 m (1H) 3.49 d (1H, J 7.7 Hz) 8.10 s (1H) 6.72 d (2H, J 8.7 Hz),
V
0.99 d (3H, J 6.7 Hz)
7.66 d (2H, J 8.8 Hz)
Table 3. 1H NMR spectra of leucine derivatives, , ppm
Comp.
no.
CH3
(CH3)2CHCH2
NaOOCCH
CHAr
Ar
Ib
0.92 d (3H, J 6.2 Hz), 1.25 1.90 m (3H) 3.21 t (1H, J 5.2 Hz)
0.94 d (3H, J 6.3 Hz)
VII 0.91 d (3H, J 6.1 Hz), 1.25 1.93 m (3H) 3.95 t (1H, J 7.1 Hz) 8.30 s (1H) 7.38 7.44 m (3H),
0.94 d (3H, J 6.3 Hz)
VIII 0.92 d (3H, J 6.2 Hz), 1.47 1.91 m (3H) 4.00 t (1H, J 7 Hz)
0.94 d (3H, J 6.3 Hz)
7.75 7.84 m (2H)
8.70 s (1H) 7.28 7.42 m (3H),
8.03 8.13 m (1H)
IX
0.90 d (3H, J 6.2 Hz), 1.25 1.90 m (3H) 3.95 t (1H, J 7 Hz)
0.93 d (3H, J 6.3 Hz)
8.28 s (1H) 7.40 d (2H, J 8.8 Hz),
7.78 d (2H, J 8.6 Hz)
X
0.92 d (3H, J 6.2 Hz), 1.45 1.91 m (3H) 4.02 t (1H, J 7 Hz)
0.96 d (3H, J 6.1 Hz)
8.37 s (1H) 6.71 6.83 m (2H),
7.21 7.35 m (2H)
XI
0.92 d (3H, J 6.0 Hz), 1.35 1.90 m (3H) 3.95 t (1H, J 7 Hz)
0.94 d (3H, J 6.1 Hz)
8.12 s (1H) 6.72 d (2H, J 8.7 Hz),
7.64 d (2H, J 8.7 Hz)
1
The structure of the products was proved by H
deuterometanol solutions, reference TMS. The mass
spectra were measured on an MKh-1320 instrument,
ionizing energy 35 eV.
NMR (Tables 2 and 3) and IR spectroscopy, mass
spectrometry, and elemental analysis. The IR spectra
contain, along with absorption bands typical of alkyl,
aryl, and carboxy groups, absorption bands at 1630
Sodium salt of valine (Ia). Metallic sodium,
0.23 g, was added to 50 ml of anhydrous methanol.
After all sodium had dissolved, the solution was
cooled to room temperature, and a solution of 1.17 g
of valine in 50 ml of methanol was added to it. The
reaction mixture was stirred for 6 h, filtered, and
concentrated in a vacuum. Ether, 100 ml, was added,
and the precipitate that formed was filtered off,
washed with ether, and dried in a vacuum. Reprecipi-
tation from methanol gave 1.25 g (90%) of compound
Ia, mp 228 230 C. Found, %: C 43.31; H 7.45; N
9.98. C5H10NNaO2. Calculated,%: C 43.17; H 7.24;
N 10.07.
1
1645 cm , characteristic of C=N vibrations [6, 7].
The mass spectra all lack molecular ion peaks. The
most abundant peaks in all the spectra belong to
RCH(CO)CN+, RCHCO+, NCHAr+, CHAr+, and Ar+
ions, where R = (CH3)2CH, (CH3)2CHCH2 and Ar =
C6H5, 2(4)-ClC6H4, 2(4)-HOC6H4.
EXPERIMENTAL
The IR spectra were recorded on a Protege-460
Fourier spectrophotometer in KBr. The 1H NMR
spectra were obtained on a Tesla BS-567A spectra for
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 9 2003

AZOMETHINES ON THE BASIS OF SODIUM SALTS OF VALINE AND LEUCINE
1447
Sodium salt of leucine (Ib) was prepared similarly
from 1.31 g of leucine and 0.23 g of metallic sodium.
Yield 1.36 g (89%), mp 172 174 C. Found, %: C
47.17; H 8.01; N 9.03. C6H12NNaO2. Calculated, %:
C 47.05; H 7.90; N 9.15.
bat, M.N., Vestsi Akad. Navuk Belarusi, Ser. Khim.
Navuk, 1997, no. 2, p. 55.
2. Zhuk, I.G., Nefedov, L.I., Lozhko, P.M., Smir-
nov, V.Yu., and Doroshenko, E.M., Vestsi Akad. Navuk
Belarusi, Ser. Khim. Navuk, 1997, no. 2, p. 74.
Synthesis of azomethines (general procedure). A
solution of 2.2 mmol of aldehyde to 20 ml of me-
thanol was added to a solution of 2 mmol of salt Ia or
Ib in 30 ml of absolute methanol. The reaction mix-
ture was stirred at room temperature for 48 h, filtered,
concentrated in a vacuum until precipitation began,
and treated with 100 ml of anhydrous ether. The
precipitate that formed was filtered off, washed with
ether, dried in a vacuum, and purified by reprecipita-
tion from methanol.
3. Mikhalkin, A.P., Usp. Khim., 1995, vol. 64, no. 3,
p. 275.
4. Minbaev, B.U., Shiffovy osnovaniya (Schiff Bases),
Alma-Ata: Nauka, 1980.
5. Azometiny (Azomethines), Ponomarev, S.V., Ed.,
Rostov-on-Don: Rostov. Gos. Univ., 1967.
6. Zakharov, A.N., Panova, G.V., and Zefirov, N.S.,
Zh. Obshch. Khim., 1995, vol. 65, no. 1, p. 110.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 9 2003