Synthesis of aminofuropyridines via the reaction of aminosilanes with pyridoxal

Full text of DOI:10.1134/S1070363214060322

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 6, pp. 1246–1248. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © L.K. Kibardina, L.V. Chumakov, A.V. Trifonov, E.M. Pudovik, A.R. Burilov, M.A. Pudovik, 2014, published in Zhurnal Obshchei
Khimii, 2014, Vol. 84, No. 6, pp. 1046–1048.
LETTERS
TO THE EDITOR
Synthesis of Aminofuropyridines via the Reaction
of Aminosilanes with Pyridoxal
L. K. Kibardinaa, L. V. Chumakova, A. V. Trifonova,
E. M. Pudovikb, A. R. Burilova, and M. A. Pudovika
a Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of Sciences,
ul. Akademika Arbuzova 8, Kazan, Tatarstan, 420088 Russia
e-mail: pudovik@iopc.ru
b Kazan (Volga) Federal University, Kazan, Tatarstan, Russia
Received April 10, 2014
Keywords: pyridoxal, aminosilanes, furopyridines
DOI: 10.1134/S1070363214060322
Synthesis of functionalized derivatives of pyridoxal
(vitamin B6) and their biological activity are currently
an active area of investigation [1–3].
of a catalyst. It can be assumed that the process
involves initial addition of the aminosilane at the al-
dehyde group followed by cyclization of the inter-
mediate with trimethylsilanol releasing. An alternative
route involves the reaction of acetal form of pyridoxal
[12]. Some furopyridines have been synthesized by
reacting pyridoxal in this way with secondary amines
under rigid conditions with the use of calcium hydride
[13, 14] (Scheme 1).
We studied a possibility of modifying pyridoxal
using aminosilanes and silazanes. The reactions of
aliphatic and aromatic aldehydes with aminosilanes
and silylamides of carboxylic acids occurred via
attachment of the carbonyl reagent at the Si–N bond to
form the corresponding trimethylsiloxy derivatives. In
these reactions zinc chloride, lithium perchlorate, p-
toluenesulfonic acid, and trimethylsilyl triflate were
used as catalysts [4–9]. Depending on the reaction
conditions, the interaction of aminosilanes with α,β-
unsaturated aldehydes resulted in 1,3-bis(dialkyl-
amino)alkenes or the corresponding aminals [10, 11].
The structure and composition of the products
obtained were confirmed by elemental analysis, mass
1
spectrometry, IR, H and 31P NMR spectroscopy. The
1H NMR spectra of IIIa–IIIc contained the signals of
nonequivalent endocyclic protons of the methylene
group of the furan moiety.
The same reactions with silylated primary amines
afforded pyridoxal azomethines Va–Vc (Scheme 2).
We found that pyridoxal I reacted with silylated
linear and cyclic secondary amines to afford bicyclic
furopyridinones IIIa–IIIc. The reaction proceeded at
room temperature or under short heating in the absence
1-Diethylamino-6-methyl-1,3-dihydrofuro[3,4-c]-
pyridin-7-ol (IIIa). A mixture of 1.0 g of pyridoxal I
Scheme 1.
NR1R2
OH
7
OH
CH 1
CHO
Me
Me
2
6
Me3SiNR1R2
+
O
N5
−Me3SiOH
3
N
CH2
IIIа−IIIc
CH2OH
4
IIа−IIc
I
R1 = R2 = Et (а), R1 = Me, R2 = CH2Ph (b), R1,R2-morpholine (c).
1246

SYNTHESIS OF AMINOFUROPYRIDINES VIA THE REACTION
1247
Scheme 2.
CH=N), 13.78 s (1Н, ОН). Found N, %: 11.64.
С14Н14N2O2. Calculated N, %: 11.57.
OH
CH=NR
CH2OH
Me
5-Hydroxymethyl-2-methyl-4-[(phenylethylimino)-
methyl]pyridin-3-ol (Vb) was obtained similarly from
0.7 g of pyridoxal I and 0.81 g of aminosilane IVb.
Yield 0.61 g (55%), mp 118°C. IR spectrum, ν, cm–1:
I + RNHSiMe3
IVа−IVc
N
Vа−Vc
1
1624 (C=N). H NMR spectrum (acetone-d6), δ, ppm
R = Ph (а), CH(Me)Ph (b), CH2Ph (c).
3
(J, Hz): 1.67 d (3Н, СН3СН, JHH 7.41), 2.42 s (3Н,
3
СН3С), 2.82 q (1H, CHСН3, JHH 7.41), 4.85 s (2Н,
and 0.87 g of trimethylsilyldiethylamine IIa in 10 mL
of benzene was heated at 40°C for 2 h. The precipitate
was recrystallized from diethyl ether. Yield 1.0 g
СН2О), 7.35 m (5Н, С6Н5), 7.94 s (1Н, NСНAr), 9.17 s
(1Н, CH=N), 14.12 s (1Н, ОН). Found N, %: 10.64.
С16Н18N2O2. Calculated N, %: 10.41.
1
(78%), mp 91–92°C. H NMR spectrum (acetone-d6),
δ, ppm (J, Hz): 1.07 t (6Н, СН3, 3JНН 8.22), 2.37 s (3H,
3
5-Hydroxymethyl-2-methyl-4-[(benzylimino)me-
thyl]pyridin-3-ol (Vc) was obtained similarly from
0.7 g of pyridoxal I and 0.75 g of aminosilane IVb.
CH3), 2.66–2.77 q (4Н, CH2, JНН 8.22), 4.91 d (1Hа,
2
2
CH2О, JHH 12.47), 5.01 d (1Hб, CH2О, JHH 12.47),
6.14 s (1H, СНО), 7.94 s (1H, CHAr). Found, %: C
64.75; H 8.36; N 12.19. C12H18N2O2. Calculated, %: C
64.84; H 8.16; N 12.60.
1
Yield 0.64 g (59%), mp 108–111°C. H NMR spec-
trum (acetone-d6), δ, ppm (J, Hz): 2.41 s (3Н, СН3С),
2.84 s (2H, СН2Ph), 4.85 s (2Н CH2O), 7.57 m (5Н,
С6Н5), 7.95 s (1Н, NСНAr), 9.19 s (1Н, CH=N), 14.04
s (1Н, ОН). Found N, %: 10.64. С15Н16N2O2. Calcu-
lated N, %: 10.94.
1-(N-Methyl-N-benzyl)amino-6-methyl-1,3-di-
hydrofuro[3,4-c]pyridin-7-ol (IIIb) was prepared
similarly from 0.70 g of pyridoxal I and 0.80 g of
silylamine IIb. Yield 0.61 g (55%), mp 113–114°C. 1H
NMR spectrum (acetone-d6), δ, ppm (J, Hz): 2.19 s
(3H, CH3C), 2.43 s (3Н, СН3N), 3.71 s (2H, CH2N),
The IR spectra were recorded on a Bruker Vector-
22 spectrometer in the range of 400–3600 cm–1 from
1
KBr pellets. The H NMR spectra were recorded on a
3.80 d (1На, СН2О, JHH 13.30), 4.68 d (1Нb, СН2О,
2
Bruker Avance 600 instrument operating at
600.13 MHz relative to the signals of residual protons
of the deuterated solvent. Mass spectrum (MALDI-
TOF) was obtained on an Ultraflex III TOF/TOF
Bruker instru-ment (p-nitroaniline matrix).
2JHH 13.30), 6.20 s (1Н, СНO), 7.28 m (5Н, С6Н5),
8.37 s (1Н, NСНAr). Mass spectrum, m/z: 271 [M + H]+.
Found, %: C 71.30; H 6.61; N 10.38. С16Н18N2O2.
Calculated, %: C 71.11; H 6.67; N 10.37.
1-Morpholino-6-methyl-1,3-dihydrofuro[3,4-c]-
pyridin-7-ol (IIIb) was prepared similarly from 0.63 g
of pyridoxal I and 0.69 g of silylmorpholine IIc. Yield
ACKNOWLEDGMENTS
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 12-03-
00204).
1
0.58 g (56%), mp 171–173°C. H NMR spectrum
(acetone-d6), δ, ppm (J, Hz): 2.40 s (3Н, СН3С), 3.63
m (4Н, СН2N), 5.04 m (6Н, СН2O), 6.26 s (1Н, СНО),
7.98 s (1Н, NСНAr). Found N, %: 11.64. С12Н16N2O3.
Calculated N, %: 11.86.
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