Reaction of Reformatsky reagent prepared from methyl 1- bromocyclohexanecarboxylate and zinc with substituted chalcones

Article abstract of DOI:10.1134/S1070428008070051

Methyl 1-bromocyclohexanecarboxylate reacts with zinc and substituted chalcones yielding the corresponding spiro-3,4-dihydropyran-2-one derivatives, 3-aryl-5-aryl-2-oxaspiro[5.5]undec-3-en-1-ones.

Full text of DOI:10.1134/S1070428008070051

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 7, pp. 963−964. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © N.F. Kirillov, A.G. Gavrilov, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 7, pp. 975−976.
Reaction of Reformatsky Reagent Prepared
from Methyl 1-Bromocyclohexanecarboxylate and Zinc
with Substituted Chalcones
N. F. Kirillov and A. G. Gavrilov
Perm State University, Perm, 614990 Russia
Received December 25, 2007
Abstract— Methyl 1-bromocyclohexanecarboxylate reacts with zinc and substituted chalcones yielding the
corresponding spiro-3,4-dihydropyran-2-one derivatives, 3- aryl-5- aryl-2-oxaspiro[5.5]undec-3-en-1-ones.
DOI: 10.1134/S1070428008070051
Reformatsky reagents reacting with α,β-unsaturated
ketones add either in position 1,2 of the conjugated
system or in position 1,4; therewith the products of the
1,4-addition undergo cyclization with the formation of
unsaturated lactones, derivatives of dihydropyran-2-one
(see scheme) [1].
dihydropyran-2-ones, namely, 3,5-diaryl-2-oxaspiro[5.5]-
undec-3-en-1-ones IIIa–IIIg.
Yields of reaction products attain 39–50%. The com-
position and structure of compounds obtained were prov-
ed by elemental analysis, IR and 1H NMR spectra. In the
IR spectra the characteristic absorption bands of the
carbonyl group appeared in the region 1735–1760 cm–1,
and those of the C=C bond, at 1645–1665 cm–1. The
1H NMR spectra contained signals of protons of aryl
substituents in the region 6.70–7.72 ppm, doublets of
protons at the double bond in the region 5.74–6.17 ppm,
methine protons doublets at 3.45–3.51 ppm, and the
signals from protons of the cyclohexane ring in the range
0.91–2.25 ppm.
In order to prepare similar compounds with a spiro
carbon atom we carried out a reaction of methyl 1-bromo-
cyclohexanecarboxylate with zinc and substituted
chalcones. In the first stage a Reformatsky reagent I was
formed that further added to 1,3-diaryl-2-propen-1-ones
giving intermediate compounds IIa–IIg. The latter by
an attack of a nucleophilic oxygen on the carbonyl carbon
of the ester group underwent cyclization with liberation
of zinc methylate bromide to form substituted spiro-3,4-
Scheme.
Br
ZnBr
Zn
COOMe
COOMe
I
'
Ar’
'
Ar’
Ar
'
ArCOCH CHAr’
_MeOZnBr
OZnBr
OMe
Ar
O
O
O
IIa–IIg
IIIa–IIIg
Ar = Ph, Ar' = Ph (a), 4-BrC6H4 (b), 4-ClC6H4 (c), 4-MeOC6H4 (d); Ar = 4-MeC6H4, Ar' = 4-BrC6H4 (e); Ar = 4-MeOC6H4,
Ar' = 4-BrC6H4 (f); Ar = Ar' = 4-ClC6H4 (g).
963

KIRILLOV, GAVRILOV
964
4-ClC6H4), 5.79 d (1H, =CH, J 6.5 Hz), 3.46 d (1H,
1-Phenyl-3-(3-nitrophenyl)-2-propen-1-one did not
ArCH, J 6.5 Hz), 0.96–2.21 m [10H, (CH2)5]. Found, %:
C 75.03; H 5.87; Cl 9.91. C22H21ClO2. Calculated, %:
C 74.89; H 6.00; Cl 10.05.
react with Reformatsky reagent I: From the reaction
mixture the initial chalcone was recovered.
EXPERIMENTAL
5-(4-Methoxyphenyl)-3-phenyl-2-oxaspiro[5.5]-
undec-3-en-1-one (IIId). Yield 1.60 g (46%), mp 140–
141°C. IR spectrum, ν, cm–1: 1665 (C=C), 1735 (C=O).
1H NMR spectrum, δ, ppm: 6.76–7.69 m (9H, Ph,
4-MeOC6H4), 5.86 d (1H, =CH, J 6.5 Hz), 3.75 s (3H,
MeO), 3.49 d (1H, ArCH, J 6.5 Hz), 1.02–2.21 m [10H,
(CH2)5]. Found, %: C 79.12; H 7.03. C23H24O3.
Calculated, %: C 79.28; H 6.94.
IR spectra of compounds IIIa–IIIg were recorded on
a spectrophotometer Specord 75IR from mulls in mineral
oil. 1H NMR spectra of solutions of these compounds in
CDCl3 were registered on a spectrometer Tesla BS-576A
(100 MHz), internal reference HMDS.
3,5-Diaryl-2-oxaspiro[5.5]undec-3-en-1-ones IIIa–
IIIg. To a mixture of 1.5 g of fine zinc turnings, catalytic
quantity of mercuric chloride, 1 ml of HMPA, and 10 ml
of anhydrous ethyl acetate was added dropwise at stirring
a mixture of 11 mmol of methyl 1-bromocyclohexane-
carboxylate and 10 mmol of an appropriate chalcone in
20 ml of anhydrous benzene. The reaction mixture was
boiled for 2 h, cooled, decanted from excess zinc, and
hydrolyzed with 5% solution of acetic acid. The organic
layer was separated, the reaction products were twice
extracted from the water layer into ethyl acetate. The
combined organic solution was dried with anhydrous
sodium sulfate, ethyl acetate was distilled off, and
compounds IIIa–IIIg were recrystallized from ethyl
acetate.
5-(4-Bromophenyl)-3-(4-methylphenyl)-2-
oxaspiro[5.5]undec-3-en-1-one (IIIe). Yield 2.06 g
(50%), mp 142–143°C. IR spectrum, ν, cm–1: 1665
(C=C), 1740 (C=O). 1H NMR spectrum, δ, ppm: 7.46 d,
7.31 d, 7.10 d, 6.92 d (8H, 4-MeC6H4, 4-BrC6H4,
J 8.4 Hz), 5.74 d (1H, =CH, J 6.5 Hz), 3.45 d (1H,ArCH,
J 6.5 Hz), 2.34 s (3H, Me), 1.01–2.18 m [10H, (CH2)5].
Found, %: C 67.01; H 5.55; Br 19.71. C23H23BrO2.
Calculated, %: C 67.16; H 5.64; Br 19.43.
5-(4-Bromophenyl)-3-(4-methoxyphenyl)-2-
oxaspiro[5.5]undec-3-en-1-one (IIIf). Yield 1.67 g
(39%), mp 129–130°C. IR spectrum, ν, cm–1: 1645
(C=C), 1750 (C=O). 1H NMR spectrum, δ, ppm: 7.38–
7.62 m, 6.98 d, 6.79 d (8H, 4-MeOC6H4, 4-BrC6H4,
J 8.5 Hz), 6.17 d (1H, =CH, J 6.5 Hz), 3.69 d (1H,ArCH,
J 6.5 Hz), 3.67 s (3H, MeO), 1.00–2.20 m [10H, (CH2)5].
Found, %: C 64.50; H 5.61; Br 18.59. C23H23BrO3.
Calculated, %: C 64.64; H 5.42; Br 18.70.
3,5-Diphenyl-2-oxaspiro[5.5]undec-3-en-1-one
(IIIa). Yield 1.50 g (47%), mp 140–141°C. IR spectrum,
ν, cm–1: 1645 (C=C), 1735 (C=O). 1H NMR spectrum,
δ, ppm: 6.87–7.66 m (10H, 2Ph), 5.83 d (1H, =CH,
J 6.5 Hz), 3.49 d (1H, ArCH, J 6.5 Hz), 0.98– 2.22 m
[10H, (CH2)5]. Found, %: C 83.12; H 7.06. C22H22O2.
Calculated, %: C 82.99; H 6.96.
3,5-Bis(4-chlorophenyl)-2-oxaspiro[5.5]undec-3-
en-1-one (IIIg). Yield 1.70 g (44%), mp 134–135°C. IR
spectrum, ν, cm–1: 1660 (C=C), 1760 (C=O). 1H NMR
spectrum, δ, ppm: 7.50 d, 7.23 d, 7.15 d, 6.93 d (8H,
4-ClC6H4, 4-ClC6H4, J 8.5 Hz), 5.74 d (1H, =CH,
J 6.5 Hz), 3.48 d (1H, ArCH, J 6.5 Hz), 0.91–2.25 m
[10H, (CH2)5]. Found, %: C 68.41; H 5.08; Cl 18.56.
C22H20Cl2O2. Calculated, %: C 68.23; H 5.20; Cl 18.31.
5-(4-Bromophenyl)-3-phenyl-2-oxaspiro[5.5]-
undec-3-en-1-one (IIIb). Yield 1.67 g (42%), mp 126–
127°C. IR spectrum, ν, cm–1: 1655 (C=C), 1745 (C=O).
1H NMR spectrum, δ, ppm: 7.08–7.65 m, 6.92 d (9H,
Ph, 4-BrC6H4, J 8.4 Hz), 5.78 d (1H, =CH, J 6.5 Hz),
3.47 d (1H,ArCH, J 6.5 Hz), 0.93–2.23 m [10H, (CH2)5].
Found, %: C 66.37; H 5.45; Br 19.98. C22H21BrO2.
Calculated, %: C 66.51; H 5.33; Br 20.11.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grant no.
07-03-96035).
3-Phenyl-5-(4-chlorophenyl)-2-oxaspiro[5.5]-
undec-3-en-1-one (IIIc). Yield 1.52 g (43%), mp 150–
151°C. IR spectrum, ν, cm–1: 1660 (C=C), 1740 (C=O).
1H NMR spectrum, δ, ppm: 6.87–7.72 m (9H, Ph,
REFERENCES
1. Ocampo, R. and Dolbier, W.R., Tetrahedron, 2004, vol. 60,
p. 9325
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 7 2008