Chemistry of ketoacetals: II. β,β′-Ketodiacetal and β,β′-hydroxydiacetals in reactions with amminia and amines

Article abstract of DOI:10.1007/s11178-005-0303-y

β,β′-Ketodiacetal and β,β′-hydroxydiacetals react with ammonium acetate in acetic acid to afford substituted pyridine, and with aromatic amines in the presence of hydrochloric acid form substituted pentamethine salts. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-005-0303-y

Russian Journal of Organic Chemistry, Vol. 41, No. 8, 2005, pp. 1113−1115. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 8, 2005,
pp. 1137−1139.
Original Russian Text Copyright © 2005 by Kharitonova, Panin, Belova.
Chemistry of Ketoacetals: II. β,β'-Ketodiacetal
and β,β'-Hydroxydiacetals in Reactions
withAmminia andAmines
O.V. Kharitonova, D.N. Panin, and O.N. Belova
Lomonosov State Academy of Fine Chemical Processing, Moscow, 119571Russia
e-mail: mitht@mitht.ru
Received October 4, 2004
Abstract—β,β'-Ketodiacetal and β,β'-hydroxydiacetals react with ammonium acetate in acetic acid to afford
substituted pyridine, and with aromatic amines in the presence of hydrochloric acid form substituted pentamethine
salts.
Ketoacetals and hydroxyacetals long attracted atten-
tion of researchers as polyfunctional synthons in the
organic synthesis and as precursors of biologically active
compounds [1, 2]. The presence of several electrophilic
sites of various activity suggests numerous possibilities
for these compounds in reactions with nucleophiles. We
formerly developed procedures for preparation of
β,β'-ketodiacetal [3] and β,β'-hydroxydiacetals [4] that
made it possible to study their chemical properties. Here
we report on the study of reactions of ketodiacetals and
hydroxydiacetals with ammonia and amines..
stated in [5] that this method is not suitable for the other
dialdehydes. We found that the treatment of diacetals I–
III with a solution of ammonium acetate in acetic acid at
heating to 90–100°C resulted both in substitution of the
ethoxy groups for amino group and also in elimination of
ether and hydroxy groups affording γ-substituted pyridines
IV–VI.
The occurring aromatization was confirmed by the
1
analysis of H NMR spectra of compounds obtained
where the proton signals were observed in the region
6
.5–8.5 ppm characteristic of aromatic compounds. The
type of signals in all cases was similar: doublets with
a coupling constant around 6 Hz characteristic of pyridine
rings.
It is known that treating glutaconic aldehyde acetal
with ammonium acetate affords pyridine but it has been
O
OEt
O
OEt
OEt
EtO
EtO
N
H
IV
I
C H
2 25
1
OEt OH OEt
OEt
CH COONH
3
4
+
C H
CH COOH
3
1
2
25
N
V
II
OEt OH OEt
OEt
O
OEt
EtO
EtO
O
N
VI
III
1070-4280/05/4108-1113©2005 Pleiades Publishing, Inc.

1114
KHARITONOVA et al.
The IR spectra also possess a characteristic pattern.
In the IR spectrum of pyridone IV absorption bands are
electron absorption spectrum with a maximum in the long-
wave region at 463 nm characteristic of this chromophore
system, and by H NMR spectrum where alongside the
–1
1
observed in the region 3210–2830 cm corresponding to
the stretching vibrations of NH (or OH), a vibration band
proton signals characteristic of the aromatic moiety and
polymethine chain in the region 6.5–8.0 ppm appear the
proton resonances belonging to the ethoxy group (4.25
and 1.2 ppm) of the ester fragment. A similar result was
obtained at treating hydroxydiacetal III with N-methyl-
aniline hydrochloride. Pentamethine salt VIIb isolated
from this reaction mixture possessed an absorption band
at 490 nm (in 2-propanol solution).
–
1
of the carbonyl group at 1642 cm , and a band at
–1
1
526 cm belonging to vibrations of the C=C bonds in
pyridine. The complex pattern of the IR spectrum in the
–1
region 3210–2830 cm may originate from the known
existence of tautomerism in γ-pyridones [6].
HN
O
N
OH
OEt OH OEt
EtO
EtO
OEt
The IR spectrum of pyridine VI hydrochloride may
be regarded as representative. It contains characteristic
vibration bands of the ester group (C=O at 1725, C–O–C
O
III
–1
at 1200–1100 cm ), bands belonging to vibrations of the
O
–
1
C=C in the aromatic system at 1606, and 1502 cm ,
a band of the out-of-plane bending vibrations of CH at
(
1) PhNHR, HCl
OEt
00 cm–1 revealing the presence of two contiguous
(2) KI
8
Ph
Ph
+
hydrogen atoms and thus indicating that the compound
possesses a para-substituted benzene ring (for the
heteroatom in pyridines may be regarded as a substituent
in the ring), a band characteristic of aromatic amine salt
N
N
_
I
R
R
VIIа, VIIb
R = H (a), CH (b).
–
1
+
at 2000 cm corresponding to the C–N H group vibra-
3
+
tions, and also a wide band of “ammonium” salt of N –H
vibrations in the region 2700–2500 cm .
–
1
Different reaction routes with ammonia (providing
substituted pyridine) and aromatic amines (affording
polymethine salts) may be due to the contribution of the
phenyl rings at the nitrogen atoms to the stabilization of
the conjugated polyene VII system.
The yields of compounds obtained are sufficiently high,
the initial compounds are available, the substituents
structure in the arising structures is versatile, therefore
β,β'-ketodiacetal and β,β'-hydroxydiacetals are conveni-
ent and accessible synthons for preparation of γ-sub-
stituted pyridines with various substituents in the γ-position
of the ring.
Therefore the study performed demonstrated that the
meso-substituted β,β'-hydroxydiacetals can serve as initial
compounds for preparation of meso-substituted
pentamethine salts or γ-substituted pyridines depending
on the character of amine used and on the condensation
conditions.
A dissimilar behaviour was observed in reactions of
the β,β'-hydroxydiacetals with aromatic amines. It was
previously shown [4] that the treatment of mesoalkyl-
substituted β,β'-hydroxydiacetals (among them also II)
with N-methylanilinium hydrochloride in alcoholic solution
afforded mesoalkyl-substituted pentamethine salts posses-
sing an absorption maximum in ethanol at 476.2 nm.
Hydroxyacetal III behaved in the same way.
EXPERIMENTAL
1H NMR spectra were registered on spectrometers
Bruker-200SY and Bruker-300SY (Germany) at
operating frequencies 200 and 300 MHz respectively from
On prolonged storage at room temperature of the
alcoholic solution of 1,1,5,5-tetraethoxy-3-ethoxycarbo-
methyl-3-pentanol (III) and aniline hydrochloride a penta-
methine salt VIIa formed with an ester group in a meso-
position and having an absorption band in the visible region.
The structure of compound obtained is confirmed by the
solutions in CDCl . The residual proton signals of the
3
solvent served as internal reference. IR spectra were
recorded on a spectrophotometer Shimadzu IR-435
(Japan) from thin film of substances. Electronic spectra
of compounds were taken on spectrophotometer Jasco-
UV 7800 from solutions in alcohol. The reaction progress
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005

CHEMISTRYOF KETOACETALS: II.
1115
was monitored and the compounds obtained were
identified by TLC on Silufol UV-254 plates (Czechia) in
the solvent system ethyl acetate–petroleum ether, 2:1,
for compound VI, and ethyl acetate for compound IV;
development under UV irradiation, in iodine vapor, or by
heating to 120–140°C for 2–3 min.
to 4:1. Yield 0.05 g (46%), R 0.37, mp 161–163°C (for
f
hydrochloride) {publ: mp (for hydrochloride) 165–168,
–1
162–163.5°C [9]}. IR spectrum, ν, cm : 2500– 2700
+
+
(N –H), 2000 (C–N H), 1725 (C=O), 1606, 1502
(C=Carom), 1100–1200 (C–O–C), 800 (bending Carom H).
1
H NMR spectrum, δ, ppm: 1.26 t (3H, J 6.82 Hz),
3
.62 s (2H), 4.17 q (2H, J 6.82 Hz), 7.25 δ (2H, J 5.56
1
,1,5,5-Tetraethoxy-3-pentanone (I) and 1,1,5,5-
Hz), 8.56 d (2H, J 5.56 Hz).
tetraethoxy-3-dodecyl-3-pentanol (II) were obtained
by procedures described in [4], 1,1,5,5-tetraethoxy-3-
ethoxycarbomethyl-3-pentanol (III) was prepared
as in [7].
[5-(N-Phenylamino)-3-ethoxycarbomethyl-2,4-
pentadienylidene]-N-anilinium iodide (VIIa) was
prepared from 0.0643 g (0.185 mmol) of compound III,
0
.048 g (0.367 mmol) of aniline hydrochloride in 1.2 ml
γ-Pyridone (IV). In a reaction flask 0.2 g
of anhydrous ethanol in 4 days at room temperature. Then
the solution was poured on ice acidified with 5% solution
of HCl, and 0.060 g of potassium iodide was added. The
separated crystals were filtered off, washed with water
and petroleum ether. Yield 0.0472 g (60.5%), mp 123–
(
0.76 mmol) of compound I was mixed with a solution
of 0.12 g (1.53 mmol) of ammonium acetate in 1.5 ml of
glacial acetic acid. The mixture was heated for 30 min at
0–100°C and then cooled to room temperature. Acetic
acid was removed by azeotropic distillation with carbon
tetrachloride. The residue was subjected to thin layer
chromatography on a plate with aluminum oxide, eluent
9
1
25°C, λmax 463 nm (2-propanol).
[5-(N-Methyl-N-phenylamino)-3-ethoxycarbo-
ethyl acetate. Yield 0.055 g (76%), R 0.30, mp 146–
methyl-2,4-pentadienylidene]-N-methylanilinium
iodide (VIIb) was similarly obtained from 0.3 g
(0.856 mmol) of compound III, 0.246 g (1.7 mmol) of
N-methyl-aniline hydrochloride in 1.2 ml of anhydrous
ethanol in 14 h at room temperature. Yield 0.030 g
(51%), λmax 490 nm (2-propanol). The hygroscopicity
of the product prevented measuring of the melting point.
f
1
1
48°C (publ.: mp 148.5°C [8]). H NMR spectrum, δ,
ppm: 2.1 (1H, the signal position considerably changed
depending on the solvent where the substance was
recorded), 6.39 br.d (2H, J 6.24 Hz), 7.74 br.d (2H,
J 6.24 Hz).
γ-Dodecylpyridine (V) was obtained in a similar
way from 0.21 g (0.486 mmol) of compound II and solution
of 0.075 g (0.97 mmol) of ammonium acetate in 1 ml of
glacial acetic acid. The residue after evaporating the
solvents was mixed with 5 ml of 21% HCl solution in
anhydrous ether. The separated crystals were filtered
off, washed with anhydrous ether and benzene. The free
base was obtained by adding 0.015 g of NaOH in 6 ml
of methanol. Yield 0.046 g (39%), mp 124–125°C (for
REFERENCES
1. Tamura, T., Kondo, H.,Annoura, H., Takeuchi, R., and Fujio-
ka, H., Tetrahedron Lett., 1986, vol. 27, p. 81.
2. Tiecco, M., Testaferri, L., Tingoli, M., and Bartoli, D., J. Org.
Chem., 1990, vol. 55, p. 4523.
3. Makin, S.M., Kruglikova, R.I., Kharitonova, O.V., and
Arshava, B.M., Zh. Org. Khim., 1991, vol. 27, p. 67.
4. Kruglikova, R.I., Kharitonova, O.V., Alieva, Z.M., and
Arshava, B.M., Zh. Org. Khim., 1995, vol. 31, p. 87.
5. General Organic Chemistry, Kochetkov, N.K., Ed., vol. 8.
Moscow: Khimiya, 1985, 751 p.
1
hydrochloride). H NMR spectrum, δ, ppm: 0.89 t (3H,
J 7.96 Hz), 1.25–1.57 m (20 H), 2.55 t (2H, J 7.62 Hz),
7
.19 d (2H, J 5.50 Hz), 8.39 d (2H, J 5.50 Hz). Found,
%
: C 70.35; H 10.40; N 5.03. C H N · HCl. Calculated,
17 29
%
: C 71.88; H 10.68; N 4.93.
γ-Ethoxycarbomethylpyridine (VI) was obtained
6
. Nakanisi, K., Infrakrasnye spektry i stroenie organi-
cheskikh soedinenii (IR Spectra and Structure of Organic
Compounds), Moscow: Mir, 1965, 207 p.
in a similar way from 0.24 g (0.69 mmol) of compound
III and solution of 0.11 g (1.35 mmol) of ammonium
acetate in 1.5 ml of glacial acetic acid. The solution was
heated for 1 h 45 min. The residue after evaporating the
solvents was subjected to chromatography on a column
packed with aluminum oxide, gradient elution with a
mixture of petroleum ether with ethyl acetate, from 10:1
7. Kharitonova, O.V., Alieva, Z.M., and Arshava, B.M., Zh.
Nauchn. i Prikl. Fotografii, 1997, vol. 42, no. 3, vol. 56.
8. Disctionary of Organic Compounds, Oxford Iniversity Press,
Translated under the title Slovar’ organicheskikh
soedinenii, vol. 2. Moscow: Inostr. Lit., 1949, 891 p.
9. Beilst., 1979, vol. 20, no. 5, 64.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 8 2005