Synthesis of alkyl-1,3-dihydro-3-oxobenzo[c]oxepine-4-carboxylates

Article abstract of DOI:10.1134/S1070428010020120

Alkyl-1,3-dihydro-3-oxobenzo[c]oxepine-4-carboxylates were obtained by bromination of dialkyl-2-(2-methylbenzylidene)malonates with N-bromosuccinimide followed by the cyclization of dialkyl-2-(2-bromomethylbenzylidene) malonates.

Full text of DOI:10.1134/S1070428010020120

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 216−217. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.A. Glukhov, N.F. Kirillov, 2009, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 2, pp. 222−223.
Synthesis
of Alkyl-1,3-dihydro-3-oxobenzo[c]oxepine-4-carboxylates
A.A. Glukhov and N. F. Kirillov
Perm State University, Perm, 614990 Russia
e-mail: kirillov@psu.ru
Received December 2, 2008
Abstract—Alkyl-1,3-dihydro-3-oxobenzo[c]oxepine-4-carboxylates were obtained by bromination of dialkyl-2-(2-
methylbenzylidene)malonates with N-bromosuccinimide followed by the cyclization of dialkyl-2-(2-bromo-
methylbenzylidene)malonates.
DOI: 10.1134/S1070428010020120
The information on the synthesis of substituted esters
of oxepinecarboxylic acids is scanty. For instance, methyl
esters of substituted oxepinecarboxylic acids are meta-
bolites of the enzymatic epoxidation of substituted methyl
benzoates [1–3], a substituted ethyl 2-oxo-2,5-dihydro-
benzo[b]oxepine-3-carboxylate is obtained alongside the
other products in reaction of diazoacetaldehyde dimethyl
acetal with ethyl coumarin-3-carboxylate [4].
ene)malonate (IIa). At heating compound IIa for 1 h at
190°C bromomethane liberated, and a cyclization
occurred providing methyl 1,3-dihydro-3-oxobenzo-
[c]oxepine-4-carboxylate (IIIa). The other esters IIIb–
IIIf were obtained without isolation of intermediate
products IIb–IIf (see the scheme). The temperature of the
reaction mixture and heating time were adjusted according
the liberation of the corresponding alkyl bromide.
We prepared alkyl-1,3-dihydro-3-oxobenzo[c]-
oxepine-4-carboxylates along the following procedure.
The bromination of dimethyl 2-(2-methylbenzylid-
ene)malonate (Ia) with N-bromosuccinimide (NBS) led
to the formation of dimethyl 2-(2-bromomethylbenzylid-
The composition and structure of compounds IIa,
IIIa–IIIf were confirmed by elemental analyses, IR and
1H NMR spectra. The IR spectra of compounds IIIa–
IIIf contain characteristic absorption bands of carbonyl
groups of ester fragments at 1705–1715 cm–1 and lactone
fragments in the region 1730–1745 cm–1, and also bands
of C=C bonds in the region 1660–1680 cm–1. In the
1H NMR spectra characteristic singlets from vinyl protons
=C=CH– and of protons of the methylene groups attached
to the benzene ring appear at δ 7.96–8.11 and 4.99–
5.07 ppm respectively.
Scheme.
H
H
COOAlk
COOAlk
COOAlk
COOAlk
C C
C C
NBS
CH3
CH2Br
IIа_IIf
EXPERIMENTAL
Iа_If
IR spectra of compounds IIa, IIIa–IIIf were recorded
COOAlk
O
on a spectrophotometer Specord 75IR from mulls in
mineral oil. H NMR spectra were registered from
1
Δ
solutions in CDCl3 on spectrometers Tesla BS-576A
(operating frequency 100 MHz) (compounds IIa, IIIa,
IIIb, IIId) and Mercury Plus-300 (operating frequency
300 MHz) (compounds IIIc, IIIe, IIIf), internal
reference HMDS (δ 0.05 ppm).
_AlkBr
O
IIIа_IIIf
Alk = Me (a), Et (b), Pr (c), i-Pr (d), Bu (e), i-C5H11 (f).
216

SYNTHESIS OF ALKYL-1,3-DIHYDRO-3-OXOBENZO[c]OXEPINE-4-CARBOXYLATES
217
Dialkyl
2-(2-bromomethylbenzylidene)-
1H NMR spectrum, δ, ppm: 1.01 t (3H, CH3, J 7.2 Hz),
1.78 m (2H, OCH2CH2CH3, J 7.2 Hz), 4.28 t (2H,
OCH2CH2, J 7.2 Hz), 5.07 s (2H, CH2Ar), 7.44– 7.58 m
(4Harom), 8.12 s (1H, CH=). Found, %: C 68.12; H 5.56.
C14H14O4. Calculated, %: C 68.28; H 5.73.
malonates (IIa–IIf). General procedure. A solution
of 0.1 mol of compound Ia–If, 0.1 mol of N-bromo-
succinimide, and 0.1 g of azobisisobutyronitrile in 60 ml
of anhydrous tetrachloromethane was boiled in the light
till the disappearance of N-bromosuccinimide. On cooling
the succinimide was filtered off, washed with CCl4 (20 ml),
the organic layer was washed with H2O and dried with
Na2SO4. On evaporating the solvent compound IIa was
recryatallized from ethanol. Compounds IIb–IIf were
used for preparation of compounds IIIb–IIIf without
additional purification.
Isopropyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIId) was obtained from compound IId at
210°C over 2.5 h. Yield 13.3 g (54%), mp 91–92°C. IR
spectrum, ν, cm–1: 1745, 1705 (C=O), 1660 (C=C).
1H NMR spectrum, δ, ppm: 1.34 d [6H, OCH(CH3)2,
J 5.6 Hz], 4.99 s (2H, CH2Ar), 5.09 m [1H, OCH(CH3)2],
7.33–7.46 m (4Harom), 7.96 s (1H, CH=). Found, %:
C 68.39; H 5.62. C14H14O4. Calculated, %: C 68.28;
H 5.73.
Dimethyl 2-(2-bromomethylbenzylidene)-
malonate (IIa). Yield 26.6 g (85%), mp 80–81°C. IR
spectrum, ν, cm–1: 1720 (C=O), 1660 (C=C). 1H NMR
spectrum, δ, ppm: 3.65 s (3H, MeO), 3.82 s (3H, MeO),
4.44 s (2H, CH2Br), 7.14–7.40 m (4Harom), 8.02 s (1H,
CH=). Found, %: C 48.38; H 3.94; Br 26.48.
C12H12BrO4. Calculated, %: C 48.02; H 4.03; Br 26.62.
Butyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIIe) was obtained from compound IIe at
215°C over 4 h. Yield 18.0 g (69%), mp 59– 60°C. IR
spectrum, ν, cm–1: 1745, 1705 (C=O), 1670 (C=C). 1H
NMR spectrum, δ, ppm: 0.96 t (3H, CH3, J 7.3 Hz), 1.45 m
(2H, CH2CH2CH3), 1.73 m (2H, OCH2CH2CH2), 4.31 t
(2H, OCH2CH2, J 6.8 Hz), 5.06 s (2H, CH2Ar), 7.44–
7.57 m (4Harom), 8.11 s (1H, CH=). Found, %: C 69.01;
H 6.36. C15H16O4. Calculated, %: C 69.22; H 6.20.
Alkyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylates IIIa–IIIf. General procedure. Com-
pounds IIa–IIf were heated at 190–220°C with
simultaneous distilling off the alkyl bromide. The reaction
product was distilled in a vacuum (1 mm Hg) and
recrystallized from a mixture benzene–hexane, 1 : 1. The
yield was calculated with respect to the amount of
compound Ia–If brought into the reaction.
Isopentyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIIf) was obtained from compound IIf at
220°C over 5 h. Yield 12.3 g (45%), mp 57–58°C. IR
spectrum, ν, cm–1: 1735, 1705 (C=O), 1665 (C=C).
1H NMR spectrum, δ, ppm: 0.96 d [6H, CH(CH3)2,
J 6.6 Hz], 1.64 q (2H, CH2CH2CH, J 6.8 Hz), 1.77 m
[1H, CH2CH(CH3)2], 4.34 t (2H, OCH2CH2, J 7.0 Hz),
5.06 s (2H, CH2Ar), 7.44–7.60 m (4Harom), 8.10 s (1H,
CH=). Found, %: C 69.88; H 6.46. C16H18O4. Calculated,
%: C 70.06; H 6.61.
Methyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIIa) was obtained from compound IIa at
190°C over 1 h. Yield 16.4 g (77%), mp 81– 82°C. IR
spectrum, ν, cm–1: 1735, 1715 (C=O), 1680 (C=C).
1H NMR spectrum, δ, ppm: 3.86 s (3H, MeO), 5.00 s
(2H, CH2Ar), 7.30–7.46 m (4Harom), 8.04 s (1H, CH=).
Found, %: C 65.91; H 4.73. C12H10O4. Calculated, %:
C 66.05; H 4.62.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
07-03-96035).
Ethyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIIb) was obtained from compound IIb at
200°C over 1.5 h. Yield 17.4 g (75%), mp 105– 106°C.
IR spectrum, ν, cm–1: 1730, 1715 (C=O), 1660 (C=C).
1H NMR spectrum, δ, ppm: 1.36 t (3H, CH3, J 7.0 Hz),
4.32 q (2H, OCH2CH3, J 7.0 Hz), 5.07 s (2H, CH2Ar),
7.33–7.45 m (4Harom), 8.07 s (1H, CH=). Found, %:
C 67.01; H 5.34. C13H12O4. Calculated, %: C 67.24;
H 5.21.
REFERENCES
1. Boyd, D.R. and Berchtold, G.A., J. Am. Chem. Soc., 1979,
vol. 101, p. 2470.
2. Boyd, D.R. and Berchtold, G.A., J. Am. Chem. Soc., 1978,
vol. 100, p. 3958.
3. Boyd, D.R., Sharma, N.D., Harrison, J.S., Malone, J.F.,
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Biomol. Chem., 2008, vol. 6, p. 1251.
4. Abdallah, H., Gree, R., and Carrie, R., Bull. Soc. Chim., 1984,
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Propyl 1,3-dihydro-3-oxobenzo[c]oxepine-4-
carboxylate (IIIc) was obtained from compound IIc at
205°C over 2 h. Yield 17.7 g (72%), mp 101– 102°C. IR
spectrum, ν, cm–1: 1740, 1705 (C=O), 1665 (C=C).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010