Alkylation of methyl 4-chloro-3-oxobutanoate with di- and tribromoalkanes

Article abstract of DOI:10.1134/S1070428017070247

Alkylation of methyl 4-chloro-3-oxobutanoate with 1,2-dibromoethane, 1,3-dibromopropane, and 1,2,3-tribromopropane afforded the corresponding dimethyl 2,5-dioxocyclohexane-1,4-dicarboxylate enol ethers.

Full text of DOI:10.1134/S1070428017070247

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 7, pp. 1099–1101. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © V.M. Ismailov, G.G. Ibragimova, N.D. Sadykhova, I.A. Mamedov, F.N. Nagiev, N.N. Yusubov, 2017, published in Zhurnal
Organicheskoi Khimii, 2017, Vol. 53, No. 7, pp. 1084–1086.
SHORT
COMMUNICATIONS
Alkylation of Methyl 4-Chloro-3-oxobutanoate
with Di- and Tribromoalkanes
V. M. Ismailov, G. G. Ibragimova, N. D. Sadykhova, I. A. Mamedov,
F. N. Nagiev, and N. N. Yusubov*
Baku State University, ul. Z. Khalilova 23, Baku, AZ-1148 Azerbaijan
*
e-mail: yniftali@gmail.com
Received March 17, 2017
Abstract—Alkylation of methyl 4-chloro-3-oxobutanoate with 1,2-dibromoethane, 1,3-dibromopropane, and
,2,3-tribromopropane afforded the corresponding dimethyl 2,5-dioxocyclohexane-1,4-dicarboxylate
1
enol ethers.
DOI: 10.1134/S1070428017070247
We have studied reactions of methyl 4-chloro-3-
oxobutanoate (1) with 1,2-dibromoethane, 1,3-di-
bromopropane, and 1,2,3-tribromopropane under basic
conditions. Ester 1 reacted with 1,2-dibromoethane and
enol ethers 2 and 3. In fact, ester 1 in DMSO in the
presence of K CO at 20°C was converted to diketone
2
3
4 which reacted with 1,2-dibromoethane and 1,3-dibro-
mopropane to afford compounds 2 and 3 (Scheme 2).
Unlike our results, Luo and Cornell [1] reported
C,C-dialkylation of 4 with formation of bicyclo[2.2.2]-
octane and bicyclo[3.2.2]nonane derivatives.
1
,3-dibromopropane in DMSO in the presence of
excess potassium carbonate at 35‒40°C to give enol
ethers of dimethyl 2,5-dioxocyclohexane-1,4-dicarbox-
ylate, dimethyl 2,5-bis(2-bromoethoxy)cyclohexa-2,5-
diene-1,4-dicarboxylate (2) and dimethyl 2,5-bis-
Apart from enol ethers 2 and 3, the alkylation of 1
with 1,2-dibromoethane and 1,3-dibromopropane was
accompanied by formation of a considerable amount of
a glassy polymer which was presumed to be polycon-
densation product of compounds 2 and 3 with diester
4. The structure and properties of the isolated polymer
require special study. Elevated temperature in the
alkylation of 1 with dibromoalkanes favored formation
(
3-bromopropoxy)cyclohexa-2,5-diene-1,4-dicarbox-
ylate (3), respectively (Scheme 1). Obviously, the
reaction involves initial self-condensation of methyl
4
-chloro-3-oxobutanoate (1) with formation of di-
methyl 2,5-dioxocyclohexane-1,4-dicarboxylate (4),
and the subsequent O-alkylation of the latter yields
Scheme 1.
COOMe
O
BrCH CH Br
Br
2
2
Br
O
COOMe
O
O
K CO , DMSO
2
3
2
Cl
OMe
COOMe
1
O
Br
BrCH CH CH Br
2
2
2
Br
O
COOMe
3
1
099

1
100
ISMAILOV et al.
Scheme 2.
COOMe
O
O
O
K CO , DMSO
Br(CH ) Br
2
3
2 n
2
, 3
Cl
n = 2, 3
OMe
O
1
COOMe
4
of the polymeric product, while the yield of 2 and 3
potassium carbonate in 50 mL of DMSO. The mixture
decreased.
was stirred for 3 h at 20°C, for 5 h at 35‒40°C, and for
5
h at 60‒70°C, and it changed from yellow to brown.
Methyl 4-chloro-3-oxobutanoate (1) in the presence
The mixture was cooled, diluted with water, and
extracted with diethyl ether (3×50 mL). The combined
extracts were dried over anhydrous MgSO and evapo-
rated under reduced pressure, and the residue was
crystallized from ethanol–hexane.
of a large excess of K CO was converted to hydro-
2
3
quinone dipotassium salt 5a, and acidification of the
latter gave dimethyl 2,5-dihydroxybenzene-1,4-dicar-
boxylate (5b) (Scheme 3). Compound 5a showed in
4
1
the H NMR spectrum two singlets at δ 3.7 and
7
.25 ppm, which were assigned to methoxy groups and
Dimethyl 2,5-bis(2-bromoethoxy)cyclohexa-2,5-
diene-1,4-dicarboxylate (2) was synthesized from 9 g
(0.06 mol) of compound 1 and 11 g (0.06 mol) of
1,2-dibromoethane. Yield 6.8 g (38%), mp 115‒117°C.
1
aromatic protons, respectively. In the H NMR spec-
trum of 5b, a singlet at δ 9.8 ppm (OH) was observed
in addition to the above signals. The structure of 5b
was also confirmed by X-ray analysis.
1
H NMR spectrum, δ, ppm: 3.40 s (2H, 1-H, 4-H),
3
.73 t (4H, CH Br), 3.76 s (6H, CH O), 4.35 t (4H,
2
Alkylation of β-dicarbonyl compounds with
,2,3-tribromopropane is known as a convenient
2 3
1
3
CH O), 7.38 s (2H, 3-H, 6-H). C NMR spectrum,
δC, ppm: 31.98, 52.94, 70.58, 117.45, 126.00, 151.09,
1
method for the synthesis of substituted furans [2].
However, the alkylation of 1 and 4 with 1,2,3-tribro-
mopropane under analogous conditions afforded enol
ether 6 (Scheme 4). In this case, no polymeric product
was formed because of the low reactivity of vinylic
bromine atom.
166.25. Found, %: C 39.41; H 4.76; Br 35.63.
C
H16Br
O
6
. Calculated, %: C 38.18; H 3.67; Br 36.36.
14
2
Dimethyl 2,5-bis(3-bromopropoxy)cyclohexa-
,5-diene-1,4-dicarboxylate (3) was synthesized from
g (0.06 mol) of compound 1 and 12.5 g (0.06 mol) of
2
9
Alkylation of methyl 4-chloro-3-oxobutanoate
with dibromoalkanes (general procedure). 1,2-Di-
bromoethane or 1,3-dibromopropane, 0.06 mol, was
added with stirring to a mixture of 0.06 mol of methyl
1,3-dibromopropane. Yield 7.4 g (32%), mp 122°C.
1
H NMR spectrum, δ, ppm: 2.75 m (4H, CH ), 3.40 s
2
(2H, 1-H, 4-H), 3.70 t (4H, CH Br), 3.75 s (6H,
2
CH O), 4.35 t (4H, CH O), 7.30 s (2H, 3-H, 6-H).
3
2
1
3
4
-chloro-3-oxobutanoate (1) and 0.12 mol of calcined
C NMR spectrum, δ , ppm: 31.98, 52.94, 70.58,
C
Scheme 3.
COOMe
OK
COOMe
OH
O
O
K CO
HCl
2
3
Cl
OMe
KO
HO
1
COOMe
COOMe
5
a
5b
Scheme 4.
COOMe
O
COOMe
Br
BrCH CHBrCH Br
2
2
O
O
O
K CO , DMSO
CH2
2
3
or
Cl
H C
2
OMe
O
O
COOMe
Br
COOMe
1
4
6
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 7 2017

ALKYLATION OF METHYL 4-CHLORO-3-OXOBUTANOATE
1101
1
17.45, 126.00, 151.09, 166.25. Found, %: C 40.41;
added to a mixture of 17 g (0.12 mol) of potassium
carbonate and 5 g (0.03 mol) of compound 1 in 50 mL
of DMSO. The mixture spontaneously warmed up and
was cooled to 15°C and stirred for 3 h while raising the
temperature stepwise from 30 to 70°C. Yield 8.2 g
H 4.26; Br 35.11. C H Br O . Calculated, %:
C 41.02; H 4.20; Br 34.18.
1
6
20
2
6
Dimethyl 2,5-dioxocyclohexane-1,4-dicarbox-
ylate (4). Ester 1, 10 g (0.06 mol), was added with
stirring to a mixture of 17 g (0.12 mol) of potassium
carbonate and 50 mL of DMSO, and the mixture was
stirred for 3 h at room temperature and for 10 h at
(
46%), mp 122°C.
b. 1,2,3-Tribromopropane, 1.4 g (0.005 mol), was
added to a mixture of 2 g (0.015 mol) of potassium
carbonate and 1.5 g (0.005 mol) of compound 4 in
20 mL of DMSO. The mixture was stirred for 1 h at
room temperature and for 5 h at 70°C. It was then
cooled, treated with HCl, and extracted with diethyl
ether. The extract was dried over Na SO and evaporat-
6
0°C. The mixture was cooled, diluted with water, and
filtered, and the filtrate was extracted with diethyl
ether. The extract was dried over MgSO , and the
solvent was distilled off. Yield 14 g (52%), yellow
crystals, mp 152‒153°C. H NMR spectrum, δ, ppm:
4
1
2
4
3
.20 s (2H, CH ), 3.80 s (3H, CH O), 3.90 s (3H,
ed, and the brown crystals were treated with ethyl
2
3
CH O), 7.45 s (1H, CH=), 9.80 s (1H, OH), 12.10 s
acetate to obtain compound 6 as white crystals. Yield
1.3 g (21%), mp 122°C. H NMR spectrum, δ, ppm:
3
1
3
1
(
1H, OH). C NMR spectrum (CDCl ), δ , ppm:
3
C
2
1
8.42, 52.33, 53.07, 95.94, 118.00, 120.05, 151.32,
68.00, 171.36. Found, %: C 52.78; H 5.17. C H O .
3.85 s (6H, CH O), 4.80 s (4H, CH O), 5.75 s (2H,
3
2
CH =), 6.16 s (2H, CH =), 7.40 s (2H, CH=).
10
12
6
2
2
1
3
Calculated, %: C 52.63; H 5.26.
C NMR spectrum, δ
C
, ppm: 52.73, 72.86, 117.00,
1
20.00, 125.00, 150.00, 166.00. Found, %: C 42.11;
Dimethyl 2,5-dihydroxybenzene-1,4-dicarbox-
ylate (5b). Stirring of a mixture of 10 g (0.06 mol) of
ester 1 and 40 g (0.28 mol) of potassium carbonate in
H 3.32; Br 34.89. C H Br O . Calculated, %:
C 41.37; H 3.44; Br 34.48.
1
6
16
2
6
1
13
1
00 mL of DMSO was accompanied by heat evolution
The H and C NMR spectra were recorded on
a Bruker AV-300 spectrometer at 300 and 75 MHz,
and change of color with formation of a viscous mate-
rial (dipotassium salt 5a) which was acidified with
respectively, using DMSO-d as solvent and tetra-
6
aqueous HCl to obtain compound 5b. Yield 7.8 g
methylsilane as internal standard.
1
(
41%), mp 158‒160°C. H NMR spectrum, δ, ppm:
REFERENCES
3
.86 s (6H, CH O), 7.26 s (2H, Harom), 9.66 s (2H,
3
1
3
OH). C NMR spectrum, δ , ppm: 53.10, 118.00,
C
1
2
. Luo, Y. and Cornell, A.J., Angew. Chem., Int. Ed., 2010,
vol. 49, p. 2750.
. Akhmedov, Sh.T., Sadykhov, N.S., Ismailov, V.M.,
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Zefirov, N.S., Chem. Heterocycl. Compd., 1986, vol. 22,
no. 12, p. 1291.
1
20.46, 151.02, 167.81. Found, %: C 52.68; H 4.57.
C H O . Calculated, %: C 53.09; H 4.42.
1
0
10
6
Dimethyl 2,5-bis[(2-bromoprop-2-en-1-yl)-
oxy]cyclohexa-2,5-diene-1,4-dicarboxylate (6).
a. 1,2,3-Tribromopropane, 9.5 g (0.033 mol), was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 7 2017