Investigation of reaction of dimedone and ethyl acetoacetate with 1,2-epoxy-3-chloropropane

Article abstract of DOI:10.1134/S1070428010110072

Reactions of dimedone and ethyl acetoacetate with 1,2-epoxy-3-chloropropane in the presence of K₂CO₃ in DMSO medium were investigated. The reaction of 1,2-epoxy-3-chloropropane with ethyl acetoacetate afforded ethyl 5-hydroxy-2-methy

Full text of DOI:10.1134/S1070428010110072

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 11, pp. 1658−1661. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.M. Magerramov, F.N. Nagiev, I.G. Mamedov, M.A. Allakhverdiev, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46,
No. 11, pp. 1652−1654.
Investigation of Reaction of Dimedone
and Ethyl Acetoacetate with 1,2-Epoxy-3-chloropropane
A. M. Magerramov, F. N. Nagiev, I. G. Mamedov, and M. A. Allakhverdiev
Baku State University, Baku, AZ-114 Azerbaijan
e-mail: fnnorgsynthes@yahoo.com
Received June 20, 2009
Abstract—Reactions of dimedone and ethyl acetoacetate with 1,2-epoxy-3-chloropropane in the presence of
K2CO3 in DMSO medium were investigated. The reaction of 1,2-epoxy-3-chloropropane with ethyl acetoacetate
afforded ethyl 5-hydroxy-2-methyl-5,6-dihydro-4H-pyran-3-carboxylate, with dimedone, 3-(1',2'-epoxypropyl-
oxy)-5,5-dimethyl-cyclohex-2-en-1-one.
DOI: 10.1134/S1070428010110072
1
In reactions of some haloderivatives with β-dicarbonyl
compounds and their derivatives in the presence of K2CO3
in different phases may form products of C- and O-
alkylation [1–7]. We showed that in the reaction of ethyl
acetoacetate with 1,2-epoxy-3-chloropropane formed
ethyl 5-hydroxy-2-methyl-5,6-dihydro-4H-pyran-3-
carboxylate (I) (Scheme 1).
one methine group. In the COSY H–1H spectrum the
presence of cross-peak 1.18 (CH3)/4.05 ppm (OCH2)
confirms the spin-spin coupling between the protons of
the ethyl group. The cross-peaks at 2.56/2.77 and 2.56,
2.77/4.61 ppm prove the geminal coupling between the
protons of the CH2 contiguous to the double bond, and
also the coupling between the protons of this CH2 and
1
The structure of compound I was established from
the data of elemental analysis, the IR, 1H and 13C NMR
spectroscopy, in particular, with the use of DEPT, COSY,
and HMQC spectra.
CH groups. In the H NMR spectrum the signal of the
hydroxy proton appeared as a triplet in agreement with
the COSY spectrum where a cross-peak was present be-
tween the protons of groups OCH2 (3.46 ppm) and OH
(4.89 ppm). The HMQC spectrum is characterized by
the lack of the corresponding carbon atom proving the
The DEPT-135 spectrum showed the presence in the
pyran I molecule of two methyl, three methylene, and
Scheme 1.
CH3
O C
CH3
K2CO3, DMSO,
70_75°C
O C
H
H
_
K+
CH2
+
+
ClCH2
CH2
CH
ClCH2
CH2
C
C
O C
O
O C
O
OCH2CH3
OCH2CH3
OCH2CH3
C O
CH3
CH3
CH3
_
C O
Cl
C O CH2
C OH
H
H
CH3
C CH2 CH
H2C
C CH2 C CH2
C O
O_
OCH2CH3
C CH2
C
CH2
_
O
O
C
O
O
C
O
CH
HO
C
OCH2CH3
OCH2CH3
H2
I
1658

INVESTIGATION OF REACTION OF DIMEDONE
1659
assignment of this signal to the hydroxy group. Besides
the spectrum contained cross-peaks between the protons
OCH2 (3.46 ppm) and CH (4.61 ppm).
propyloxy)-5,5-dimethylcyclohex-2-en-1-one (III)
(Scheme 3).
1
The H NMR spectrum of compound III contains
singlets at 0.92, 2.05, 2.18, 5.18 ppm characteristic of
methyl, methylene, and =CH groups of dimedone respec-
tively; the multiplets observed at 2.57–2.73 and 3.16 ppm
are assigned to CH2 and CH groups of the epoxide respec-
tively, and the doublets at 3.56 and 4.01 ppm, belong to
the protons of OCH2 group. The structure of compound
III was also confirmed by IR and 13C NMR spectra (see
EXPERIMENTAL).
The IR spectrum of the synthesized compound I
is characterized by the strong absorption bands of the
stretching vibrations of groups OH (3420 cm–1) and C=O
(1685 cm–1) of the ester moiety.
The presence in the molecule of the hydroxy group
was also confirmed in a chemical way. To this end
ethyl 5-hydroxy-2-methyl-5,6-dihydro-4H-pyran-3-
carboxylate was reacted with acetyl chloride to obtain
ethyl 5-acetyloxy-2-methyl-5,6-dihydro-4H-pyran-3-
carboxylate (II) (Scheme 2).
The reaction of compound III with o-toluidine gave
the corresponding aminoalcohol, 1-(N-2'-methylphenyl-
amino-)-3-O-(4',4'-dimethylcyclohex-1-en-6-on-2-yl)
propanol (IV) (Scheme 4).
In the 1H NMR spectrum of compound IV the proton
signals of the CH and CH2 groups are shifted downfield
compared to these groups in the epoxy ring of com-
pound III (from 3.16 to 4.79 ppm and from 2.57–2.73 to
3.18 ppm respectively) proving the involvement in the
reaction with the nucleophile of the oxirane fragment. In
The lack in the 1H NMR spectrum of the OH group
signal at 4.89 ppm, the singlet at 2.21 ppm belonging
13
to CH3 group and also the appearance in the C NMR
spectrum of the signal from the carbonyl carbon atom at
169.03 ppm confirm the structure II.
The product of the reaction of the enol form of dim-
edone with 1,2-epoxy-3-chloropropane is 3-(1',2'-epoxy-
Scheme 2.
OC2H5
OC2H5
C O
CH3
O
C
CH3
H2C
HC
50_60°C
_HCl
O
H2C
HC
HO
+
C
CH3
O
O
Cl
C
O
C
H2
H2
O
C CH3
II
Scheme 3.
H
OCH2
C
CH2
OH
O
O
O
K2CO3, DMSO, 70_75°C
_HCl
H3C
H3C
H3C
H3C
H3C
H3C
O
H
+
ClCH2
CH2
C
O
O
III
Scheme 4.
H
H
H
C
OCH2
C
CH2
N
OCH2
O
CH2
H3C
H3C
O
H3C
H3C
C2H5OH
OH
+
H2N
H3C
H3C
O
IV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 11 2010

MAGERRAMOV et al.
1660
the 1H NMR spectrum of the reaction product alongside
the characteristic signals of the protons of the aryl frag-
ment and dimedone the singlets are present at 3.42 (OH),
3.81 (NH), and a doublet at 3.99 ppm (OCH2).
4.82 m (1H, CH). 13C NMR spectrum (CCl4), δ, ppm:
13.98 (CH3CH2), 14.55 (CH3), 20.09 (CH3COO), 32.25
(CH2), 59.01 (OCH2CH3), 65.54 (OCH2), 78.98 (CH),
102.05 (C3), 164.65 (C2), 167.20 (COO), 169.03 (COO).
Found, %: C 57.63; H 6.84. C11H16O5. Calculated, %:
C 57.89; H 7.07.
EXPERIMENTAL
5,5-Dimethyl-3-(2-oxiranylmethoxy)-2-cyclohexen-
1-one (III). To 60 ml of DMSO was added 35 g of K2CO3,
and the mixture was stirred for 15 min. To the mixture
42.06 g (0.30 mol) of dimedone was added, and the stir-
ring was continued for 30 min, then 27.75 g (0.30 mol)
of 1,2-epoxy-3-chloropropane was added, and the stirring
at 50–60°C was performed for 20 h. The reaction mixture
was diluted with distilled water and extracted with ether.
The extract obtained was dried with Na2SO4, ether was
distilled off, the residue was distilled in a vacuum. Yield
22 g (37%), bp 143°C (1 mm Hg), nD20 1.5050, Rf 0.57
(eluent heptane–2-propanol, 3:2). IR spectrum, ν, cm–1:
1710, 1230, 1015. 1H NMR spectrum (CDCl3), δ, ppm:
0.92 s (6H, 2CH3), 2.05 s (2H, CH2), 2.18 s (2H, CH2),
2.57 and 2.73 m (2H, CH2), 3.16 m (1H, CH), 3.56 d and
4.01 d (2H, OCH2), 5.18 s (1H, =CH). 13C NMR spectrum
(CDCl3), δ, ppm: 27.81 (2CH3), 33.12 (C5), 41.91 (CH2),
43.89 (CH2), 48.94 (CHO in the ring), 51.05 (CH2O in the
ring), 69.21 (CH2O), 102.79 (=CH), 175.74 (C3), 199.96
(CO). Found, %: C 67.12; H 8.47. 11H16O3. Calculated,
%: C 67.32; H 8.22.
IR spectra were registered on a spectrophotometer Var-
ian 3600 FT-IR from liquid films, 1H and 13C NMR spec-
tra were recorded on a spectrometer Bruker Avance-300
at operating frequencies 300 and 75 MHz. Elemental
analyses were performed on a CHN analyzer Hewlett
Packard 185. The purity of compounds was proved by
TLC on Silufol UV-254 plates.
Ethyl 5-hydroxy-2-methyl-5,6-dihydro-4H-pyran-
3-carboxylate (I). To 55 ml of DMSO was added 35 g
of K2CO3, and the mixture was stirred for 20 min. Then
to the reaction mixture 39.06 g (0.30 mol) of ethyl ace-
toacetate was added, and the stirring was continued for
30 min. The temperature in this interval increased to 35°C.
Then 27.75 g (0.30 mol) of 1,2-epoxy-3-chloropropane
was added, and the reaction mixture was stirred for 1 h at
20°C. The mixture heated to 70–75°C and was stirred at
this temperature for 25 h. Then the mixture was diluted
with distilled water and extracted with ether. The extract
obtained was dried with Na2SO4, ether was distilled
off, the residue was distilled in a vacuum. Yield 29 g
(52%), bp 144°C (1 mm Hg), nD20 1.4930, Rf 0.18 (eluent
heptane–2-propanol, 3:2). IR spectrum, ν, cm–1: 3420,
1685. 1H NMR spectrum (DMSO-d6), δ, ppm: 1.18 t (3H,
CH3, 3J 6.89 Hz), 2.09 s (3H, CH3), 2.56 and 2.77 m (2H,
CH2), 3.46 m (2H, OCH2), 4.05 q (2H, OCH2, 3J 6.89 Hz),
4.61 m (1H, CH), 4.89 t (1H, OH, 3J 5.52 Hz). 13C NMR
spectrum (DMSO-d6), δ, ppm: 14.96 (CH3CH2), 14.98
(CH3), 32.25 (CH2), 59.95 (OCH2CH3), 64.77 (OCH2),
83.89 (OCH), 102.93 (C3), 165.91 (C2), 167.93 (COO).
Found, %: C 58.27; H 7.35. C9H14O4. Calculated, %:
C 58.05; H 7.58.
3-[2-Hydroxy-3-(2-toluidino)propoxy]-5,5-
dimethyl-2-cyclohexen-1-one (IV). To a mixture of
2 g (0.01 mol) of compound III and 2.5 g (0.023 mol)
of o-toluidine was poured 15 ml of C2H5OH, and the
mixture was stirred for 15 h at 65–70°C. Then ethanol
was distilled off from the reaction mixture. The liquid
residue crystallized at standing. The crystals obtained
were washed with CCl4. Yield 1.95 g (63%), mp 145°C,
Rf 0.38 (eluent heptane–2-propanol, 5:1). IR spectrum,
ν, cm–1: 3315, 3440, 1700. 1H NMR spectrum (DMSO-
d6), δ, ppm: 1.0 s (6H, 2CH3), 2.19 s (4H, 2CH2), 2.28 s
(3H, CH3–Carom), 3.18 d (2H, CH2N), 3.42 s (1H, OH),
3.81 s (1H, NH), 3.99 d (2H, CH2O), 4.79 m (1H, HCO),
Ethyl 5-acetoxy-2-methyl-5,6-dihydro-4H-pyran-
3-carboxylate (II). A mixture of 3 g (16 mmol) of
compound I and 2.5 g (32 mol) of acetyl chloride was
stirred for 20 min at 50–60°C, then it was left stand-
ing for 24 h and afterwards it was distilled. Yield 2.4 g
(65%), bp 59°C (1 mm Hg), nD20 1.4712, Rf 0.29 (eluent
13
5.32 s (1H, =CH), 6.48–6.99 (4Harom). C NMR spec-
trum (DMSO-d6), δ, ppm: 18.72 (CH3), 28.41 (2CH3),
31.87 (C5), 42.85 (CH2), 46.78 (CH2), 51.93 (CH2N),
67.21 (CHO), 71.73 (CH2O), 102.11 (=CH), 109.98 (CHa-
rom), 117.12 (CHarom), 122.84 (Carom), 127.14 (CHarom),
130.04 (CHarom), 147.21 (Carom), 177.18 (C3), 198.81
(CO). Found, %: C 71.47; H 8.07; N 4.83. C18H25NO3.
Calculated, %: C 71.26; H 8.30; N 4.62.
1
heptane–2-propanol, 3 : 2). H NMR spectrum (CCl4),
δ, ppm: 1.34 t (3H, CH3), 2.13 s (3H, CH3), 2.21 s (3H,
CH3), 2.65 and 2.99 m (2H, CH2), 4.15 m (4H, 2CH2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 11 2010

INVESTIGATION OF REACTION OF DIMEDONE
1661
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