Pyridoxal-derived Schiff's bases

Full text of DOI:10.1134/S1070363215020309

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 2, pp. 514–516. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © L.K. Kibardina, A.V. Trifonov, E.M. Pudovik, A.R. Burilov, M.A. Pudovik, 2015, published in Zhurnal Obshchei Khimii, 2015,
Vol. 85, No. 2, pp. 345–347.
LETTERS
TO THE EDITOR
To the 80th Anniversary of B.I. Ionin
Pyridoxal-Derived Schiff’s Bases
L. K. Kibardinaa, A. V. Trifonovb, E. M. Pudovikc, A. R. Burilova, and M. A. Pudovika
a Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
e-mail: pudovik@iopc.ru
b Kazan National Research Technological University, Kazan, Tatarstan, Russia
c Kazan (Volga Region) Federal University, Kazan, Tatarstan, Russia
Received December 8, 2014
Keywords: pyridoxal, amine, azomethine, tautomerism
DOI: 10.1134/S1070363215020309
Over the past few decades synthesis of func-
tionalized derivatives of pyridoxal (vitamin B6) and
study of their biological activity have received a great
deal of interest [1–3]. Among these compounds, mono-
and bis-azomethines of pyridoxal occupy an important
place [4–6]. In practice, pyridoxal hydrochloride is
often used since free pyridoxal is unstable and
undergoes irreversible fast transformation.
further supported by the absence of carbonyl group
absorption in the IR spectrum.
Pyridoxal is known to react readily with primary
aliphatic and aromatic amines to form the
corresponding azomethines that may exist in two
tautomeric forms as well: the aminoacetal and the
aldimine [1].
Different substituents at the nitrogen atom can
preferentially stabilize one of the tautomeric forms.
According to our data, the aniline-derived azomethine
III existed in the aldimine form. Its IR spectrum
contained an absorption band at 1613 cm–1 assigned to
Reaction of pyridoxal hydrochloride with sodium
bicarbonate affords free pyridoxal I (mp 191°C).
The available data on the structure of pyridoxal are
contradictory: either cyclic hemiacetal form Ib [7, 8]
or the aldehyde Ia [9] have been suggested as possible
alternatives (Scheme 1).
1
the C=N bond. The H NMR spectrum contained a
singlet at 9.35 ppm corresponding to the methine
proton. Substitution of the phenyl group with pyridyl
stabilized the aminoacetal form IIIb as evidenced by
the presence of absorption band at 3201 cm–1 (N–H) in
the IR spectrum and the absence of the methine proton
(CH=N) signal in the 1H NMR spectrum.
Since azomethines are usually obtained in alcoholic
1
or aqueous medium, we examined H NMR spectra of
pyridoxal recorded in D2O and MeOH-d4 solutions.
Analysis of the spectral data indicated the existence of
pyridoxal in hemiacetal form in those solvents, being
Scheme 1.
OH
CH
OH
OH
OH
CHO
H3C
H3C
H3C
CHO
NaHCO3
O
N
N
N
C
CH2OH
CH2OH
H2
HCl
Ia
Ib
514

515
PYRIDOXAL-DERIVED SCHIFF’S BASES
Scheme 2.
NHR
OH
OH
CH
O
H3C
H3C
CH=NR
I + RNH2
N
N
C
CH2OH
IIIа, IIIc_IIIe
H2
IIIb
R = Ph (а), C5H4N (b), S-(–)-CH(Me)Ph (c), R-(+)-CH(Me)Ph (d), ortho-С6H4CH2OH (e).
Next, we prepared optically active azomethines IIIc
and IIId starting from R-(+)- and S-(–)-phenyl-
ethylamine, respectively; the products can later be used
for targeted synthesis of optically active functional
derivatives. Azomethine IIId, bearing ortho-positioned
hydroxymethyl group in the aromatic moiety, is of
interest for macrocyclic structures preparation.
pyridoxal and 1.1 g of α-aminopyridine in 20 mL of
ethanol was stirred during 12 h. Then the precipitate
was filtered off, washed with ethanol and diethyl ether,
and dried. Yield 1.49 g (52.8%), mp 179–180°С. IR
1
spectrum, ν, cm–1: 3201 (N–Н). Н NMR spectrum
(DMSO-d6, 20°C), δ, ppm: 2.36 s (3H, CH3), 4.92 d
2
2
(1Ha, CH2O, JHH 11.6), 5.06 d (1Hb, CH2O, JHH
1
3
According to H NMR spectra, compounds IIIc and
IIId existed in the aldimine form in solution (Scheme 2).
11.6), 6.61 d.t (1Н, СH, JHH 8.4), 6.63–6.66 m (1H,
Py), 6.88 d.d (1H, NH, JHH 7.7), 7.44–7.49 m (2H,
3
Py), 7.93 s (1H, CHAr), 8.05–8.07 m (1H, Py), 10.23 s
(1Н, ОН). Mass spectrum: m/z 243 [M]+. Found, %: C
63.93; H 5.78; N 17.20. C13H13N3O2. Calculated, %: С
64.20; Н 5.35; N 17.28.
3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotino-
aldehyde (I). A solution of 2.42 g of sodium hydro-
carbonate in 15 mL water was added upon stirring to a
solution of 5.86 g of pyridoxal hydrochlochloride in
10 mL of H2O. Light-yellow precipitate was formed
almost immediately. The reaction was accompanied by
gas evolution. The reaction mixture was stirred during
1 h. The precipitate was filtered off; the benzene
solution was refluxed with a Dean–Stark trap to remove
water and then dried under vacuum (0.02 mmHg)
4-[S-(–)-(1-Phenylethylimino)methyl]-5-(hydroxy-
methyl)-2-methyl-4-pyridin-3-ol (IIIc). A mixture of
1.0 g of pyridoxal, 0.72 g of R-(+)-1-phenyl-
ethylamine, and 10 mL of ethanol was stirred at 20°С
during 1 day, and then evaporated. The residue was
washed with a mixture of diethyl ether and hexane
(1:1), and dried. Yield 1.38 g (85%), mp 101–102°С,
[α]D20 –119.7° (с 0.5, acetone). IR spectrum, ν, cm–1:
1
during 1 h. Yield 4.52 g (94%), mp 191°С. Н NMR
spectrum (D2O), δ, ppm (J, Hz): 2.41 s (3H, СH3), 5.00
2
2
1
d (1Ha, CH2, JHH 13.3), 5.18 d (1Hb, CH2, JHH 13.3),
1632 (С=N), 3152 (ОН). Н NMR spectrum (acetone-
3
6.50 s (1H, СН), 7.50 с (1H, СHAr).
d6, 20°C), δ, ppm: 1.66 d (3Н, СН3, JHH 6.7), 2.43 s
(3H, CH3), 4.47 s (1H, OH), 4.78 q (1H, СНPh, JHH
6.6), 4.82 s (2H, CH2O), 7.29–7.48 m (5H, Ph), 7.94 s
(1H, CHAr), 9.17 s (1H, CH=), 14.12 br. s (1Н, ОН).
Mass spectrum: m/z 270 [M]+. Found, %: С 70.85; Н
6.41; N 10.48. C16H18N2O2. Calculated, %: С 71.11; Н
6.67; N 10.37.
5-(Hydroxymethyl)-2-methyl-4-[(phenylamino)-
methyl]pyridin-3-ol (IIIa). Aniline (0.93 g) was added
dropwise to a suspension of 1.67 g of pyridoxal in
15 mL of ethanol. Orange precipitate was filtered off,
washed with anhydrous ethanol and with diethyl ether,
and dried. Yield 1.35 g (55.8%), mp 178–179°С. IR
1
spectrum, ν, cm–1: 1613 (C=N). Н NMR spectrum
4-[R-(+)-(1-Phenylethylimino)methyl]-5-(hydroxy-
methyl)-2-methyl-4-pyridin-3-ol (IIId) was obtained
similarly from 1.00 g of pyridoxal, 0.72 g of S-(–)-1-
phenylethylamine, and 10 mL of ethanol. Yield 1.34 g
(82.7%), mp 101–102°С, [α]D20 117.2° (с 0.5, acetone).
IR spectrum, ν, cm–1: 1632 (С=N), 3152 (ОН). 1Н NMR
spectrum (acetone-d6, 20°C), δ, ppm: 1.66 d (3Н, СН3,
3JHH 6.7), 2.43 s (3H, CH3), 4.48 s (1H, OH), 4.78 q
(1Н, СНPh, JHH 6.6), 4.82 s (2H, CH2O), 7.29–7.48 m
(5H, Ph), 7.94 s (1H, CHAr), 9.17 s (1H, CH=), 14.12
(acetone-d6), δ, ppm: 2.47 s (3H, CH3), 4.51 s (1H,
OH), 4.93 s (1Ha, CH2O), 4.94 s (1Hb, CH2O), 7.34–
7.54 m (5H, Ph), 8.01 s (1H, СHAr), 9.35 s (1H, CH),
13.76 s (1H, OH). Mass spectrum: m/z 242 [M]+.
Found, %: C 69.94; H 5.63; N 10.95. C14H14N2O2.
Calculated, %: С 69.42; Н 5.79; N 11.57.
6-Methyl-1-(pyridin-2-ylamino)-1,3-dihydrofuro-
[3,4-c]pyridin-7-ol (IIIb). A mixture of 1.94 g of
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KIBARDINA et al.
br.s (1Н, ОН). Mass spectrum: m/z 270 [M]+. Found,
%: С 70.85; Н 6.41; N 10.48. C16H18N2O2. Calculated,
%: С 71.11; Н 6.67; N 10.37.
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ACKNOWLEDGMENTS
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This work was financially supported by Russian
Foundation for Basic Research (project no. 15-03-01046).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 2 2015