Synthesis and keto-enol tautomerism of 6-alkyl-1-alkoxypyridine-2,4-diones

Article abstract of DOI:10.1134/S1070428011020199

Reactions of 2,2-dimethyl-5-(3-oxoalkanoyl)-1,3-dioxane-4,6-diones with alkoxyamines proceed regioselectively at the β′-keto group of the side acyl chain affording the corresponding tricarbonyl imines whose boiling in toluene leads to the formation of products of intramolecular cyclization, N-alkoxy-2,4-dioxopyridine-3-carboxylic acids. The decarboxylition of the obtained pyridine-3-carboxylic acids in mesitylene at 160-165°C gives in the preparative yield N-alkoxypyridine-2,4-diones. Proceeding from the IR and NMR spectra the problems of the keto-enol and imine-enamine tautomerism were discussed for the series of 5-acyl derivatives of the Meldrum acid and the obtained N-alkoxypyridine-2,4-diones.

Full text of DOI:10.1134/S1070428011020199

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 2, pp. 277283. Pleiades Publishing, Ltd., 2011.
Original Russian Text  D.B. Rubinov, I.L. Rubinova, F.A. Lakhvich, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 2, pp. 284289.
Synthesis and Keto-Enol Tautomerism
of 6-Alkyl-1-Alkoxypyridine-2,4-diones
D. B. Rubinov, I. L. Rubinova, and F. A. Lakhvich
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, 220141 Belarus
e-mail: rub_irin@mail.ru
Received May 25, 2010
Abstract—Reactions of 2,2-dimethyl-5-(3-oxoalkanoyl)-1,3-dioxane-4,6-diones with alkoxyamines proceed
regioselectively at the β’-keto group of the side acyl chain affording the corresponding tricarbonyl imines whose
boiling in toluene leads to the formation of products of intramolecular cyclization, N-alkoxy-2,4-dioxopyridine-3-
carboxylic acids. The decarboxylition of the obtained pyridine-3-carboxylic acids in mesitylene at 160–165°С gives
in the preparative yield N-alkoxypyridine-2,4-diones. Proceeding from the IR and NMR spectra the problems of
the keto-enol and imine-enamine tautomerism were discussed for the series of 5-acyl derivatives of the Meldrum
acid and the obtained N-alkoxypyridine-2,4-diones.
DOI: 10.1134/S1070428011020199
metabolites of entomopathogenic fungi and which exhibit
a wide range of biological action including insecticidal,
fungicidal, antibiotic, cytostatic etc action. Inasmuch as
the hetrocyclic ring in these natural substances contains
various functional substituents, and the nitrogen atom
often is attached to a hydroxy or a methoxy group,
further studies of the synthetic potential of the tetracar-
Acylated derivatives of the Meldrum acid of type I
are convenient synthons for the preparation of substituted
2,4-pyrandiones [1, 2] and 2,4-pyridinediones [3]. Up till
now a large group of naturally occurring compounds is
described of the 2,4-pyridinedione series, like funiculosin
[4], tenellin, bassianin, pyridovericin, ilicicolin [5, 6],
militarinone [7], leporin [8], iromycin [9], etc., which are
Scheme 1.
H
.H
.
.
.
.
.
O
O
OH
O
O
O
O
O
O
O
O

'

O
R1
O
'
R1
O
R1




O
O
O
O
Ia_Ie
A
B
R2ONH2
OR2
H
H
.
H
.
.
.
.
.
.
.
.
O
O
NOR2
R1
NOR2
R1
O
O
O
O
N
O
O
O
O
R1
O
O
IIa_IIe
O
O
O
D
C
I, R1 = Me (а), Et (b), i-Bu (c), 4-MeOC6H4CH2 (d), t-BuCH2 (e); II, R1 = Me, R2 = Et (а); R1 = R2 = Et (b); R1 = i-Bu,
R2 = Et (c); R1 = 4-MeOC6H4CH2, R2 = Et (d); R1 = t-BuCH2, R2 = Bn (e).
277

RUBINOV et al.
278
bonyl compounds I appears promising for building up
the pyridinedione ring modified in various positions, in
particular, for the preparation of N-alkoxy-substituted
2,4-pyridinediones.
We also failed to observe dienol tautomer B by means of
NMR spectroscopy.
Presumably the same direction of the enolization in
the side chain is conserved also in obtained alkoxyimines
IIа–IIe. The existence of these compounds just in the
enolimine form C and not in the enolenamine form D
We formerly demonstrated [3] that 5-acetoacetyl-2,2-
dimethyl-1,3-dioxane-4,6-dione (Iа) after the treatment
with aliphatic and aromatic amines followed with boiling
first in toluene and then in dimethoxydiglyme was con-
verted in good yields into 6-methylpyridine-2,4(1Н,3Н)-
diones possessing the corresponding alkyl or aryl residue
attached to the nitrogen atom (Scheme 1).
1
is confirmed by the presence in their Н NMR spectra
of an only one-proton ОН singlet in the region 15.20–
15.30 ppm. The double set of the majority of the signals
indicates the presence in the obtained alkoxyimines
IIа–IIe of a mixture of Z,E-isomers with respect to the
oxime bond with the prevalence of the E-isomer to which
corresponds the upfield shift of the γ'-protons of the acyl
chain, whereas in the Z-isomer the α'-protons of the side
chain of the dioxanedione suffer the upfield shift.
Carrying on the research in this field we found that
compounds Iа–Ie reacted with the O-ethers of oximes
(methoxyamine, ethoxyamine, or benzyloxyamine)
regioselectively like in the case of amines [3] with the
β’-keto group of the acyl chain furnishing tricarbonyl
imines IIа–IIe in 90–95% yields.
In the IR spectra of compounds IIа–IIe the same
regularities concerning the absorption of the conjugated
carbonyl groups remain as observed in tetracarbonyl
compounds Iа–Ie, except for the absorption band of the
β'-carbonyl group of the acyl chain lacking in compounds
IIа–IIe. Note that the IR spectra of compounds Ie and
IIb recorded in the chloroform solution were virtually
indistinguishable from the respective spectra registered
in film and KBr respectively.
The assignment to the compounds obtained of the
structures IIа–IIe is complicated by their possible exis-
tence in various tautomeric forms. The tautomerism of
the Meldrum acid derivatives is poorly understood. It was
suggested that the 5-acylated Meldrum acids had a com-
pletely enolized karbonyl group of the side chain [10–12].
According to the 1Н NMR data, tetracarbonyl compounds
Iа–Ie are totally enolized as shows the one-proton singlet
of the enol proton in the region 15 ppm.Apparently these
compounds conserve the same enolization position as the
5-acylated Meldrum acids and consequently they exist in
the tautomeric form А. The assumption is supported by
the correlation of the IR spectra of 5-acylated Meldrum
acids [1] and with those of compounds Iа–Ie. In the spec-
tra of both series of compounds very strong absorption
bands appear of the weakly conjugated lactone carbonyl
at 1660–1670 cm–1 and of the conjugated double bond at
1560–1580 cm–1. β’-Carbonyl group of the side acyl chain
of compounds Iа–Ie is not enolized and is not involved
into the formation of the intramolecular hydrogen bond as
shows the corresponding absorption band at 1720 cm–1.
It was presumed that for the better understanding of
the tautomerism in this series of compounds (Scheme 2)
it would be interesting to investigate the spectral charac-
teristics of enamine derivative III synthesized by treating
compound Ic with ammonia in methanol. According to
the data of 1НNMR spectrum enamine III is completely
enolized and exists in the enamine form as show the
broadened one-proton singlets of the intramolecularly
chelated enol proton at 15.81 ppm, intramolecularly che-
lated NH proton at 8.25 ppm, and NH proton at 5.99 ppm.
In going from the tetracarbonyl compound Ic to
enamine III the character of IR spectrum considerably
changed. The absorption band in the region 1730–
1740 cm–1 characteristic of compounds I and II disap-
Scheme 2.
.
H
.
H
.
H
.
H
H
H
.
.
.
.
.
.
.
.
O
O
N
O
O
O
N
NH3
O
O
Ic
Methanol
O
O
O
IIIA
IIIB
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SYNTHESIS AND KETO-ENOL TAUTOMERISM
279
The decarboxylation of acids IVа–IVe occurs at
160–165°С at the use of mesitylene as solvent. The tar-
get 1-alkoxypyridine-2,4-diones Vа–Ve were obtained
in 85–90% yield and according to the 1Н NMR spectra
existed in solution in enol form А, as indicated by the
allyl constant Н3–Н5 2 Hz.
peared. The spectrum contains strong absorption bands
at 1645 and 1680 cm–1 in poor agreement with structure
A, but well consistent with the tautomeric form оdнаqо
B. The band at 1645 cm–1 corresponds to the conjugated
intramolecularly chelated carbonyl group in the side chain
of form B, and the band at 1680 cm–1 is characteristic of
the s-trans-conjugated lactone carbonyl. In the totally
enolized pyran-2,4-diones the absorption band of the
conjugated carbonyl group of the lactone ring is observed
at 1685–1690 cm−1 [1]. The conjugated double bonds of
enamine III give rise to strong absorption bands in the
region 1550–1560 cm–1, by 20–30 cm–1 lower than in
compounds I and II.
Thus the described reaction sequence provides
a simple and efficient preparation method of N-alkoxy
derivatives of 6-substituted pyridine-2,4-diones.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
FT IR Bomem Michelson 100, from solid substances
in pellets with KВr, from fluids in films. NMR spectra
were registered on a spectrometer Bruker Avance 500
[operating frequencies 500 (1Н) and 125 MHz (13С)]
from solutions in deuterochloroform, refernce TMS.
Mass spectra were measured on a system HPLC-MS/
MS coupled with a chromatograph Accela with a mass
detector LCQ Fleet in theAPCI ionization mode with the
detection of positive [M + 1]+ or negative [M – 1]– ions.
Melting points were determined on a Boёtius heating
block. The reaction progress was monitored and the purity
of compounds obtained was checked by TLC on Silufol
UV-254 or Alufol UV-254 (Merck) plate, development
under the UV irradiarion with subsequent spraying with
iron(III) chloride. The column chromatography was car-
ried out on silica gel Kieselgel 60 HF254 TLC-standar
(Merck) and Kieselgel 60 (Fluka).
The comparison of the 13С NMR spectra of com-
pounds I–III also provides arguments supporting the
difference in the enolization direction in these structures.
For instance, in teteracarbonyl compounds Iа–Ie and
tricarbonyl imines IIа–IIe the signal of the atom С5
of the dioxane ring appears in the region 92–93 ppm,
whereas the same signal of enamine III is shifted upfield
(81.97 ppm).
Thus the analysis of the spectral characteristics of
compound III confirms the assumption that compounds
I and II exist just in the tautomeric forms A and C re-
spectively.
The boiling of alkoxyimines IIа–IIe in toluene results
in the intramolecular cyclization into N-alkoxy-2,4-
dixopyridine-3-carboxylic acids IVа–IVe, and entering
into the reaction of the enaminoketone form D seems
more preferable than the reaction of the ketoimine form
C. Compounds IVа–IVe according to the 1Н NMR data
are completely enolized, and their structure is stabilized
by two intramolecular hydrogen bonds, as indicate two
narrow one-proton singlets in the region 12 and 14 ppm
(Scheme 3).
Compounds Iа–Ie were synthesized by method [1].
2,2-Dimethyl-5-(3-oxobutanoyl)-1,3-dioxane-4,6-
dione (Iа), mp 81–82°С (ethyl acetate–petroleum ether)
(mp 81–83°С [2]) was identical in chemical and physi-
cochemical characteristics to described samples.
Scheme 3.
O
O
O
OH
O
OH


IIa_IIe
OH
Toluene
Mesitylene
R1
N
OR2
O
R1
N
OR2
R1
N
OR2
OH
R1
N
OR2
O
Va_Ve
B
IVa_IVe
A
R1 = Me (а), Et (b), i-Bu (c), 4-MeOC6H4CH2 (d), t-BuCH2 (e); II, R1 = Me, R2 = Et (а); R1 = R2 = Et (b); R1 = i-Bu, R2 =
Et (c); R1 = 4-MeOC6H4CH2, R2 = Et (d); R1 = t-BuCH2, R2 = Bn (e).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

RUBINOV et al.
280
2,2-Dimethyl-5-(3-oxopentanoyl)-1,3-dioxane-
tion of the initial compound (TLC monitoring, eluent
petroleum ether–ethyl acetate, 10:1). On completion of
the reaction the reaction mixture was washed with wa-
ter (2 × 50 ml), dried with magnesium sulfate, filtered
through a thin bed of silica gel, and the solution was
evaporated in a vacuum.
4,6-dione (Ib). Yield 75%, mp 50–51°С (ethyl acetate–
petroleum ether). IR spectrum, cm–1: 3010, 2965,
1
1750 v.s, 1720 s, 1660 s, 1560 v.s. Н NMR spectrum,
δ, ppm: 1.11 t (3Н, СН3СН2, J 7.3 Hz), 1.76 s (6Н,
CН3ССН3), 2.64 q (2Н, СН3СН2, J 7.3 Hz), 4.14 s (2Н,
СОСН2СО), 14.99 s (1Н, ОH). 13С NMR spectrum, δ,
ppm: 202.56 s, 189.18 s, 170.00 s, 160.79 s, 105.57 s,
93.39 s, 49.54 t, 36.83 t, 26.90 q, 26.90 q, 7.51 q. Found,
%: С 54.52; Н 5.94. C11H14O6. Calculated, %: С 54.54;
Н 5.83.
2,2-Dimethyl-5-[3-(ethoxyimino)butanoyl]-1,3-
dioxane-4,6-dione (IIа). Yield 93%. Oily substance. IR
spectrum, cm–1: 2980, 1740 v.s, 1660 s, 1590 v.s, 1570 v.s.
1Н NMR spectrum, δ, ppm (mixture of Z,E-isomers,
~1:1): 1.19 t and 1.22 t (3Н, CН3СH2, J 7.0 Hz), 1.75
s (6Н, CН3ССН3), 1.94 s and 1.99 s (3Н, CН3СH=N),
3.97 s and 4.09 s (2Н, CОСH2), 4.03–4.08 m (2Н,
ОCН2СH3), 15.31 br.s (1Н, ОН). Found, %: С 53.21;
Н 5.07; N 5.21. [M + 1]+ 272. C12H17NO6. Calculated,
%: С 53.13; Н 6.32; N 5.16. M 271.27.
2,2-Dimethyl-5-(5-methyl-3-oxohexanoyl)-1,3-
dioxane-4,6-dione (Ic). Yield 82%, mp 70–75°С (ethyl
acetate–petroleum ether). IR spectrum, cm–1: 3010, 2960,
1
1745 v.s, 1720 s, 1680 s, 1565 v.s. Н NMR spectrum,
δ, ppm: 0.95 d (6Н, СН3СНСН3, J 6.7 Hz), 1.76 s (6Н,
CН3ССН3), 2.19 m (1Н, СН3СНСН3), 2.49 d (2Н,
СН2СН, J 6.9 Hz), 4.13 s (2Н, СОСН2), 14.97 br.s (1Н,
ОH). 13С NMR spectrum, δ, ppm: 201.67 s, 189.08 s,
169.99 s, 160.75 s, 105.52 s, 93.47 s, 52.46 t, 50.25 t,
26.87 q, 26.87 q, 24.36 d, 22.46 q, 22.46 q. Found, %:
С 57.62; Н 6.68. [M – 1]– 269. C13H18O6. Calculated, %:
С 57.77; Н 6.71. M 270.28.
2,2-Dimethyl-5-[3-(ethoxyimino)pentanoyl]-1,3-
dioxane-4,6-dione (IIb). Yield 96%. Oily substance.
IR spectrum, cm–1: 2985, 1740 v.s, 1660 s, 1600 v.s,
1570 s, 1520 s. 1Н NMR spectrum, δ, ppm (mixture of
Z,E-isomers, ~1:1): 1.08 t and 1.12 t (3Н, CН3СH2С=N,
J 7.5 Hz), 1.16–1.22 m (3Н, CН3СH2О), 1.73 s and 1.74 s
(6Н, CН3ССН3), 2.32 q and 2.41 q (2Н, CН3CН2С=N,
J 7.5 Hz), 3.73 q and 4.04 q (2Н, CН3СH2О, J 7.0 Hz),
3.95 s and 4.07 s (2Н, СОCН2), 15.33 s and 15.28 s (1Н,
ОН). 13С NMR spectrum, δ, ppm: 193.08 s, 192.91 s,
170.52 s, 170.45 s, 160.36 s, 160.19 s, 156.37 s, 153.79 s,
105.13 s, 105.06 s, 92.56 s, 91.66 s, 69.29 t, 69.24 t,
39.87 t, 35.70 t, 28.52 t, 26.86 q, 26.86 q, 26.79 q,
26.79 q, 22.40 t, 14.55 q, 14.48 q, 10.66 q, 9.85 q. Found,
%: С 54.54; Н 6.84; N 5.02. [M + 1]+ 286. C13H19NO6.
Calculated, %: С 54.73; Н 6.71; N 4.91. M 285.30.
2,2-Dimethyl-5-[4-(4-methoxyphenyl)-3-oxo-
butanoyl]-1,3-dioxane-4,6-dione (Id). After subjecting
to column chromatography on silica gel (eluent ethyl
acetate–petroleum ether) yield 55%. Oily substance.
IR spectrum, cm–1: 2950, 1750 s, 1720 s, 1610 s,
1570 s, 1240 s. 1Н NMR spectrum, δ, ppm: 1.72 s (6Н,
CН3ССН3), 3.75 s (2Н, CН2С6H4), 3.78 s and 3.82 s (3Н,
ОCН3), 4.14 s (2Н, СОCН2), 6.82 d [2Н, 3',5'-(H)2-C6H4,
J 8.5 Hz], 7.15 d [2Н, 2',6'-(H)2-C6H4, J 8.5 Hz], 15.14 s
(1Н, ОН).
2,2-Dimethyl-5-[5-methyl-3-(methoxyimino)-
hexanoyl]-1,3-dioxane-4,6-dione (IIc). Yield 90%. Oily
substance. IR spectrum, cm–1: 2980, 1740 v.s, 1670 v.s,
1665 v.s, 1580 v.s, 1570 v.s, 1555 m 1Н NMR spectrum,
δ, ppm (mixture of Z,E-isomers, ~1:2): 0.94–0.96 m (6Н,
CН3ССН3), 1.75 s (6Н, CН3ССН3), 1.87–1.98 m (6Н,
CН3СНСН3), 2.17 d and 2.30 d (2Н, CН2СH, J 7.1 Hz),
3.76 s and 3.80 s (3Н, ОСН3), 3.95 s and 4.07 s (2Н,
CОСН2), 15.23 s and 15.34 s (1Н, ОН). 13С NMR spec-
trum, δ, ppm: 192.70 s, 192.53 s, 170.52 s, 170.39 s,
160.38 s, 160.27 s, 155.17 s, 152.71 s, 105.14 s, 105.10 s,
92.78 s, 91.64 s, 61.55 q, 61.46 q, 43.97 t, 40.49 t, 37.88 t,
35.60 t, 26.82 q, 26.82 q, 26.76 q, 26.76 q, 25.87 d,
25.54 d, 22.64 q, 22.64 q, 22.41 q, 22.41 q. Found, %:
С 56.30; Н 6.98; N 4.72. [M + 1]+ 300. C14H21NO6.
Calculated, %: С 56.18; Н 7.07; N 4.68. M 299.33.
2,2-Dimethyl-5-(5,5-dimethyl-3-oxohexanoyl)-
1,3-dioxane-4,6-dione (Ie). Oily substance. Yield
78%. IR spectrum, cm–1: 2955, 2870, 1740 v.s, 1670 s,
1
1585 v.s. Н NMR spectrum, δ, ppm (monoenol): 1.05
s [9Н, С(СН3)3], 1.75 s (6Н, CН3ССН3), 2.51 s [2Н,
СН2С(СН3)3], 4.13 s (2Н, СОСН2СО), 14.89 s (1Н,
ОH); (dienol, 15%): 1.05 s [9Н, С(СН3)3], 1.79 s (6Н,
CН3ССН3), 2.68 s [2Н, СН2С(СН3)3], 6.79 s (1Н,
СН=С), 10.95 s (1Н, ОH), 17.20 s (1Н, ОH). Found, %:
С 59.32; Н 7.12. [M + 1]+ 285. C14H20O6. Calculated, %:
С 59.14; Н 7.09. M 284.31.
Reaction of ketones Iа–Ie with alkoxyamines. To
a solution of 0.02 mol of ketone Iа–Ie in 50 ml of chlo-
roform was added 0.022 mol of alkoxyamine, and the
stirring was carried out for 7–8 h till complete consump-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SYNTHESIS AND KETO-ENOL TAUTOMERISM
281
2,2-Dimethyl-5-[4-(4-methoxyphenyl)-3-(ethoxy-
imino)butanoyl]-1,3-dioxane-4,6-dione (IId). Yield
92%. Oily substance. IR spectrum, cm–1: 2985, 2940,
1740 v.s, 1670 s, 1610 m, 1585 v.s, 1510 v.s, 1250 v.s.
1Н NMR spectrum, δ, ppm (mixture of Z,E-isomers,
~1 : 1): 1.21 t and 1.26 t (3Н, CН3СH2О, J 7.0 Hz), 1.69 s
(6Н, CН3ССН3), 3.59 s and 3.75 s (2Н, CН2С6H4), 3.77 s
and 3.78 s (3Н, ОCН3), 3.84 s and 3.96 s (2Н, СОCН2),
4.11 q and 4.12 q (2Н, CН3CН2О, J 7.0 Hz), 6.81 d
and 6.83 d [2Н, 3',5'-(H)2-C6H4, J 8.5 Hz], 7.11 d and
7.14 d [2Н, 2',6'-(H)2-C6H4, J 8.5 Hz], 15.24 br.s (1Н,
ОН). Found, %: С 60.48; Н 6.28; N 3.86. [M + 1]+ 378.
C19H23NO7. Calculated, %: С 60.47; Н 6.14; N 3.71.
M 377.40.
cooled to room temperature, passed through a thin bed of
silica gel, and the solution was placed for several hours
into a refrigerator at –18°C. The separated crystals were
filtered off, washed with toluene, and dried in a vacuum.
6-Methyl-2,4-dioxo-1-ethoxy-1,2,3,4-tetrahydro-
pyridine-3-carboxylic acid (IVа). Yield 53%. Yellowish
crystals, mp 129–131°С. IR spectrum, cm–1: 3000,
1
1695 v.s, 1620 s, 1600 v.s, 1500 s. Н NMR spectrum,
δ, ppm: 1.44 t (3Н, CН3СН2, J 7.1 Hz), 2.46 s (3Н,
CН3C=СН), 4.32 q (2Н, CН3CН2О, J 7.1 Hz), 6.01 s
(1Н, CН3C=СН), 13.20 s (1Н, СООН), 14.48 s (1Н,
ОН). 13С NMR spectrum, δ, ppm: 172.16 s, 171.76 s,
162.22 s, 151.51 s, 101.00 d, 96.85 s, 73.26 t, 17.78 q,
13.15 q. Found, %: С 50.93; Н 5.35; N 6.44. [M + 1]+
214. C9H11NO5. Calculated, %: С 50.70; Н 5.20; N 6.57.
M 213.19.
5-{3-[(Benzyloxy)imino]-5,5-dimethyl-hexanoyl}-
2,2-dimethyl-1,3-dioxane-4,6-dione (IIe). Yield 90%.
Oily substance. IR spectrum, cm–1: 2985, 2960, 1740 v.s,
1670 s, 1610, 1565 v.s, 1530 s, 1250 v.s. 1Н NMR spec-
trum, δ, ppm (mixture of dandасtереоmеров, ~3 : 1):
0.99 s and 1.01 s [9Н, (CН3)3С], 1.55 s and 1.68 s (6Н,
CН3ССН3), 2.25 s and 2.42 s [2Н, CН2С(CН3)3], 3.96 s
and 4.08 s (2Н, СОCН2), 4.98 s and 5.03 s (2Н, CН2О),
7.24–7.35 m (5Н, C6H5), 15.30 br.s (1Н, ОН). Found,
%: С 64.92; Н 6.98; N 3.67. [M + 1]+ 390. C21H27NO6.
Calculated, %: С 64.77; Н 6.99; N 3.60. M 389.45.
2,4-Dioxo-6-ethyl-1-ethoxy-1,2,3,4-tetrahydro-
pyridine-3-carboxylic acid (IVb). Yield 65%. Yellowish
crystals, mp 102–105°С. IR spectrum, cm–1: 3005, 2980,
1
1700 v.s, 1615 s, 1595 v.s, 1495 s. Н NMR spectrum,
δ, ppm: 1.32 t (3Н, CН3СН2С, J 7.4 Hz), 1.44 t (3Н,
CН3СН2О, J 7.0 Hz), 2.78 q (2Н, CН3CН2С, J 7.4 Hz),
4.32 q (2Н, CН3CН2О, J 7.0 Hz), 6.01 s (1Н, C=СH),
13.22 s (1Н, СООН), 14.49 s (1Н, ОН). 13С NMR spec-
trum, δ, ppm: 171.94 s, 162.26 s, 156.37 s, 145.99 s,
134.09 s, 99.19 d, 73.37 t, 23.97 t, 13.16 q, 11.50 q. Found,
%: С 52.99; Н 5.69; N 6.28. [M + 1]+ 228. C10H13NO5.
Calculated, %: С 52.86; Н 5.77; N 6.16. M 227.22.
5-(3-Amino-5-methylhex-2-enoyl)-2,2-dimethyl-
1,3-dioxane-4,6-dione (III). To a solution of 2.70 g
(10 mmol) of reagent Ic in 20 ml of methanol was added
5 ml of 25% water solution of ammonia, the mixture was
stirred for 10 h at room temperature, and evaporated in
a vacuum. The residue was extracted with chloroform, the
extract was washed with 1% HCl, with water, dried with
anhydrous magnesium sulfate, ane evaporated on a rotary
evaporator. Yield 2.15 g (80%), mp 127–128°С (ethyl
acetate–petroleum ether). IR spectrum, cm–1: 3410, 3315,
3245, 2960, 1680 v.s, 1645 s, 1560 v.s, 1550 v.s. 1Н NMR
spectrum, δ, ppm: 1.00 d (6Н, CН3СНСН3, J 6.6 Hz),
1.71 s (6Н, CН3ССН3), 2.01 m (1Н, СН), 2.21 br.d (2Н,
CН2СH, J 7.5 Hz), 5.99 br.s (1Н, NН), 6.46 d (1Н, C=СН,
J 1.7 Hz), 8.25 br.s (1Н, NН···О), 15.81 br.s (1Н, ОН).
13С NMR spectrum, δ, ppm: 181.23 s, 171.70 s, 169.91 s,
161.71 s, 103.39 s, 90.69 d, 81.97 s, 47.46 t, 28.43 d,
26.36 q, 26.36 q, 22.31 q, 22.31 q. Found, %: С 58.08;
Н 7.23; N 5.24. [M – 1]– 268. C13H19NO5. Calculated,
%: С 57.98; Н 7.11; N 5.20. M 269.30.
6-Isiobutyl-1-methoxy-2,4-dioxo-1,2,3,4-tetra-
hydropyridine-3-carboxylic acid (IVc). Yield 62%. Oily
substance. IR spectrum, cm–1: 2990, 1700 v.s, 1610 s,
1
1595 v.s, 1495 s. Н NMR spectrum, δ, ppm: 1.01 d
(6Н, CН3СНCН3, J 6.6 Hz), 2.08 m (6Н, CН3СНCН3),
2.58 d (2Н, СН2CH, J 7.2 Hz), 4.09 s (3Н, ОСН3),
5.97 s (1Н, 5-CH), 13.21 s (1Н, СООН), 14.42 s (1Н,
ОН···О=СОН). Found, %: С 52.99; Н 5.69; N 6.28. [M +
1]+ 242. C11H15NO5. Calculated, %: С 54.77; Н 6.27;
N 5.81. M 241.25.
6-(4-Methoxybenzyl)-2,4-dioxo-1-ethoxy-1,2,3,4-
tetrahydropyridine-3-carboxylic acid (IVd). Yield
57%, mp 122–123°С. IR spectrum, cm–1: 2990, 1700 v.s,
1
1615 s, 1595 v.s, 1500 s. Н NMR spectrum, δ, ppm:
1.39 t (3Н, CН3СН2, J 7.0 Hz), 3.82 s (3Н, ОСН3), 4.00 s
(2Н, CH2C6H4), 4.20 q (2Н, СН3CH2, J 7.0 Hz), 5.79 d
(1Н, С=СН), 6.91 d (2Нm, C6H4, J 8.7 Hz), 7.15 d (2Но,
C6H4, J 8.7 Hz), 13.20 s (1Н, СООН), 14.47 s (1Н, ОH).
13С NMR spectrum, δ, ppm: 172.11 s, 171.71 s, 162.27 s,
159.21 s, 154.51 s, 130.32 d, 130.32 d, 125.78 s, 114.55 d,
Pyridinecarboxylic acids IVа–IVe. A solution of
10 mmol of alkoxyimine IIа–IIe in 50 ml of toluene
was heated at reflux for 0.5 h. The reaction mixture was
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114.55 d, 101.31 d, 96.94 s, 73.31 t, 55.34 q, 36.03 t,
13.12 q. Found, %: С 60.27; Н 5.29; N 4.56. [M + 1]+
320. C16H17NO6. Calculated, %: С 60.18; Н 5.37; N 4.39.
M 319.32.
(Vc). Yield 85%. Colorless crystals, mp 155–156°С. IR
spectrum, cm–1: 2980, 1650 s, 1605 m, 1560 v.s, 1550
v.s. 1Н NMR spectrum, δ, ppm: 0.95 d (6Н, CН3СНСН3,
J 6.5 Hz), 2.02 m (1Н, CН3СНСН3), 2.48 d (2Н, CН2СН,
J 7.0 Hz), 4.00 s (3Н, ОCН3), 5.85 d (1Н, 5-CH, J 2.5 Hz),
6.03 d (1Н, Н3, J 2.5 Hz), 11.48 br.s (1Н, ОН). 13С NMR
spectrum, δ, ppm: 167.09 s, 161.86 s, 148.49 s, 101.95 d,
98.81 d, 64.25 q, 39.63 t, 27.55 d, 22.40 q, 22.40 q. Found,
%: С 60.85; Н 7.59; N 7.22. [M + 1]+ 198. C10H15NO3.
Calculated, %: С 60.90; Н 7.67; N 7.10. M 197.24.
1-(Benzyloxy)-6-neopentyl-2,4-dioxo-1,2,3,4-
tetrahydropyridine-3-carboxylic acid (IVe). Yield
61%. Colorless crystals, mp 151–153°С. IR spectrum,
cm–1: 3090, 2965, 2910, 1695 s, 1680 s, 1620 s, 1590 v.s,
1250 s. 1Н NMR spectrum, δ, ppm: 0.94 s [9Н, (CН3)3С],
2.50 s [2Н, CН2С(CН3)3], 5.22 s (2Н, ОCН2), 5.91 s
(1Н, C=СН), 7.41–7.47 m (5Н, C6H5), 13.22 s (1Н,
СООН···О), 14.58 s (1Н, ОН). 13С NMR spectrum,
δ, ppm: 172.17 s, 171.15 s, 162.19 s, 155.05 s, 153.39
s, 132.84 d, 129.87 d, 129.87 d, 128.96 d, 128.96 d,
102.28 d, 97.14 d, 78.85 t, 43.64 t, 33.54 s, 29.67 q, 29.67
q, 29.67 q. Found, %: С 65.47; Н 6.49; N 4.36. [M + 1]+
332. C18H21NO5. Calculated, %: С 65.24; Н 6.39; N 4.23.
M 331.37.
6-(4-Methoxybenzyl)-1-ethoxypyridine-
2,4(1Н,3Н)-dione (Vd). Yield 80%. Colorless crystals,
mp 224–225°С (with carbonization). IR spectrum,
cm–1: 2985, 1650 m, 1615 m, 1545 v.s, 1515 s, 1250 v.s.
1Н NMR spectrum, δ, ppm (DMSO-d6): 1.42 t (3Н,
CН3СН2, J 7.0 Hz), 3.75 s (3Н, ОСН3), 3.89 s (2Н,
CH2C6H4), 4.08 q (2Н, СН3CH2, J 7.0 Hz), 5.47 d (1Н,
Н3, J 3.0 Hz), 5.58 s (1Н, 5-СН, J 3.0 Hz), 6.89 d [2Н,
3',5'-(H)2-C6H4, J 8.6 Hz], 7.19 d [2Н, 2',6'-(H)2-C6H4,
J 8.6 Hz], 10.48 s (1Н, ОH). 13С NMR spectrum, δ,
ppm: 164.96 s, 159.63 s, 158.12 s, 149.11 s, 130.09 d,
130.09 d, 128.18 s, 113.81 d, 113.81 d, 98.60 d, 97.67 d,
70.98 t, 54.91 q, 35.01 t, 12.91 q. Found, %: С 65.57;
Н 6.09; N 4.96. [M + 1]+ 276. C15H17NO4. Calculated,
%: С 65.44; Н 6.22; N 5.09. M 275.31.
Decarboxylation of pyridinecarboxylic acids IVа–
IVe. A solution of 5 mmol of pyridinecarboxylic acid
IVа–IVe in 20 ml of mesitylene was boiled for 3–4 h
(TLC monitoring), cooled to the room temperature, the
separated crystals were filtered off, washed with cold
chloroform, and dried in a vacuum.
6-Methyl-1-ethoxypyridine-2,4(1Н,3Н)-dione (Vа).
Yield 87%, mp 175–176°С. IR spectrum, cm–1: 2980,
1-(Benzyloxy)-6-neopentylpyridine-2,4(1Н,3Н)-
dione (Ve). Yield 83%. Yellowish crystals, mp 156–
158°С. IR spectrum, cm–1: 3070, 3035, 2960, 1645 v.s,
1600, 1565 v.s, 1550 v.s, 1255 s. 1Н NMR spectrum, δ,
ppm: 0.88 s [9Н, (CН3)3С], 2.42 s [2Н, CН2С(CН3)3],
5.16 s (2Н, ОCН2), 5.83 d (1Н, Н3, J 2.0 Hz), 6.18 d (1Н,
Н5, J 2.0 Hz), 7.34–7.47 m (5Н, C6H5), 11.51 br.s (1Н,
ОН). 13С NMR spectrum, δ, ppm: 166.85 s, 161.94 s,
147.72 s, 133.94 s, 129.79 d, 129.79 d, 129.16 d, 128.68 d,
128.68 d, 103.23 d, 99.28 d, 78.01 t, 43.33 t, 32.90 s,
29.67 q, 29.67 q, 29.67 q. Found, %: С 71.00; Н 7.29;
N 4.76. [M + 1]+ 288. C17H21NO3. Calculated, %: С 71.06;
Н 7.37; N 4.87. M 287.36.
1
1665 s, 1640 s, 1600 v.s, 1570 s, 1550 v.s. Н NMR
spectrum, δ, ppm: 1.38 t (3Н, CН3СН2, J 7.1 Hz), 2.34 s
(3Н, CН3C=СН), 4.24 q (2Н, CН3CН2О, J 7.1 Hz), 5.85 d
(1Н, H5, J 2.5 Hz), 5.98 d (1Н, Н3, J 2.5 Hz), 11.04 br.s
(1Н, ОН). 13С NMR spectrum, δ, ppm: 166.82 s,
161.83 s, 145.85 s, 101.30 d, 98.69 d, 72.25 t, 17.26 q,
13.15 q. Found, %: С 56.93; Н 6.65; N 8.24. [M + 1]+
170. C8H11NO3. Calculated, %: С 56.80; Н 6.55; N 8.28.
M 169.18.
6-Ethyl-1-ethoxypyridine-2,4(1Н,3Н)-dione (Vb).
Yield 90%. Yellowish crystals, mp 173–175°С. IR
spectrum, cm–1: 2980, 2935, 1655 s, 1605 m, 1575 s,
1550 v.s, 1535 v.s. 1Н NMR spectrum, δ, ppm (DMSO-
d6): 1.15 t (3Н, CН3СН2, J 7.4 Hz), 1.24 t (3Н, CН3СН2О,
J 7.0 Hz), 2.62 q (2Н, CН3CН2, J 7.4 Hz), 4.13 q (2Н,
CН3CН2О, J 7.0 Hz), 5.53 d (1Н, 5-CH, J 3.0 Hz),
5.64 d (1Н, 3-СН, J 3.0 Hz), 10.50 s (1Н, ОН). 13С NMR
spectrum, δ, ppm: 164.99 s, 159.31 s, 150.94 s, 97.18 d,
96.15 d, 71.00 t, 22.86 t, 12.90 q, 11.77 q. Found, %:
С 59.11; Н 7.09; N 7.62. [M + 1]+ 184. C9H13NO3.
Calculated, %: С 59.00; Н 7.15; N 7.65. M 183.21.
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