Synthesis of 5-aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-diones by reformatsky reaction

Article abstract of DOI:10.1023/A:1012453329579

Alkyl 3-(1-bromocyclohexyl)-2,2-dimethyl-3-oxopropanoates react with zinc and aromatic aldehydes to yield 5-aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-diones.

Full text of DOI:10.1023/A:1012453329579

Russian Journal of Organic Chemistry, Vol. 37, No. 6, 2001, pp. 811 813. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 6, 2001,
pp. 858 860.
Original Russian Text Copyright
2001 by Kirillov, Shchepin.
Synthesis of 5-Aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-
1,3-diones by Reformatsky Reaction
N. F. Kirillov and V. V. Shchepin
Perm State University, Perm, 614600 Russia
Received July 4, 2000
Abstract Alkyl 3-(1-bromocyclohexyl)-2,2-dimethyl-3-oxopropanoates react with zinc and aromatic
aldehydes to yield 5-aryl-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-diones.
In extension of the study on Reformatsky reaction
as a method for building up a system of 2,3,5,6-tetra-
hydro-2,4-pyrandione [1, 2] we carried out an
investigation of reaction between alkyl 3-(1-bromo-
cyclohexyl)-2,2-dimethyl-3-oxopropanoates (IIIa, b),
zinc and aromatic aldehydes Va g. The initial bromo-
ketoesters IIIa, b were prepared by reaction of
methyl or ethyl -bromoisobutyrates (Ia, b) with zinc
and cyclohexanecarbonyl chloride followed by
bromination in the acetic acid solution of methyl or
ethyl 2,2-dimethyl-3-oxo-3-cyclohexylpropanoates
(IIa, b) (see the scheme).
zinc alcoholate VI spontaneously underwent cycliza-
tion into substituted tetrahydro-2,4-pyrandiones
containing a spiro carbon in the 5 position of the
pyran ring. Thus 5-aryl-2,2-dimethyl-4-oxaspiro-
[5,5]undecane-1,3-diones (VIIa g) were prepared
(see table).
The final products were obtained in 42 72%
yield. Their composition and structure were proved
1
by elemental analysis, H NMR and IR spectra. In the
1H NMR spectra appear the characteristic proton
signals ( , ppm) in 5.53 5.81, 1.34 1.47, 0.60 2.07
regions. The resonances belong respectively to
methine proton (CHO), methyl groups protons
(Me2C), and those of the cyclohexane ring. In the IR
spectra absorption bands are present from the keto
Our study revealed that alkyl 3-(1-bromocyclo-
hexyl)-2,2-dimethyl-3-oxopropanoates were capable
to react with zinc in the ether ethyl acetate (1: 2)
medium affording a new zinc enolate IV that reacted
with aromatic aldehydes Va g. The arising bromo-
1
group in 1715 1720 cm region and from the lactone
1
carbonyl at 1740 1770 cm .
Scheme.
I IV, R1 = Me (a), Et (b); VI, R1 = Me (a), Et (b g); V VII, R2 = 4-BrC6H4 (a), 4-ClC6H4 (b), 2,4-Cl2C6H3 (c),
2-FC6H4 (d), 4-FC6H4 (e), 4-CH3OC6H4 (f), 3,4-(CH3O)2C6H3 (g).
1070-4280/01/3706-0811$25.00 2001 MAIK Nauka/Interperiodica

812
KIRILLOV, SHCHEPIN
1
Yields, physical constants, IR and H NMR spectra, and elemental analyses of 5-aryl-2,2-dimethyl-4-oxaspiro[5,5]-
undecane-1,3-diones (VIIa g)
1
Compd. Yield,
IRspectrum ( , cm )
CO ket. CO lact.
1H NMR spectrum ( , ppm)
Me2C
no.
%
mp,
C
R2
(CH2)5
CHO
VIIa
VIIb
VIIc
58
64
54
171 172
170 171
182 183
1715
1720
1725
1740
1750
1770
7.32 d, 7.62 d (4H, 4-BrC6H4) 1.36 s, 1.46 s 0.60 2.05 m 5.61 s
7.37 d, 7.42 d (4H, 4-ClC6H4) 1.34 s, 1.46 s 0.62 2.07 m 5.62 s
7.49 d, 7.55 s, 7.60 d (3H, 1.37 s, 1.47 s 0.67 2.02 m 5.81 s
2,4-Cl2C6H3)
VIId
VIIe
42
72
128 129
162 163
1720
1720
1760
1750
7.20 7.57
7.22 d.d, 7.42 d.d (4H,
4-FC6H4)
m
(4H, 2-FC6H4) 1.36 s, 1.47 s 0.74 2.04 m 5.80 s
1.35 s, 1.46 s 0.66 2.03 m 5.67 s
VIIf
VIIg
40
41
131 132
145 147
1720
1720
1750
1760
3.80 s (3H, MeO), 6.96 d, 7.29 d 1.35 s, 1.44 s 0.71 2.00 m 5.55 s
(4H, 4-MeOC6H4)
3.79 s (6H, MeO), 6.90 d, 6.92 s, 1.35 s, 1.46 s 0.76 2.01 m 5.53 s
6.97 d [3H, 3,4-(MeO)2C6H3]
Found, %
Calculated, %
Formula
Compd. no.
C
H
C
H
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
VIIg
59.26
67.48
60.68
70.95
71.15
72.01
69.21
5.85
6.63
5.62
6.88
6.92
7.71
7.52
C18H21BrO3
C18H21ClO3
C18H20Cl2O3
C18H21FO3
C18H21FO3
C19H24O4
59.19
67.39
60.85
71.03
71.03
72.13
69.34
5.80
6.60
5.67
6.95
6.95
7.65
7.57
C20H26O5
EXPERIMENTAL
ppm): 0.83 1.93 m [10H, (CH2)5], 1.16 s (6H, CH3),
2.29 m (1H, CHC=O), 3.56 s (3H, CH3O). Found,
%: C 67.74; H 9.45. C12H20O3. Calculated, %: C
67.89; H 9.50.
1H NMR spectra of compounds IIa, b, IIIa, b in
CCl4 solution were registered on RYa-2310 instru-
ment (60 MHz), and those of compounds VIIa g in
DMSO-d6 solution on spectrometer Bruker AM-300
(300 MHz), internal reference TMS. IR spectra of
individual compounds were recorded on UR-20
spectrophotometer.
Ethyl 2,2-dimethyl-3-oxo-3-cyclohexylpropano-
ate (IIb) was prepared similarly to compound IIa
proceeding from compound Ib. Yield 53%, bp
129 131 C (10 mm Hg), d240 1.0016, nD20 1.4525. IR
1
1
spectrum ( , cm ): 1715, 1730 (C=O). H NMR
spectrum ( , ppm): 0.78 1.88 m [10H, (CH2)5], 1.13
t (3H, CH3CH2O), 1.13 s (6H, CH3), 2.33 m (1H,
CHC=O), 4.05 q (2H, OCH2CH3). Found, %: C
68.91; H 9.82. C13H22O3. Calculated, %: C 68.99;
H 9.80.
Methyl 2,2-dimethyl-3-oxo-3-cyclohexylpropano-
ate (IIa). To 10 g of fine zinc turnings in
25 ml of anhydrous ether and 5 ml of anhydrous ethyl
acetate was added 0.1 mol of methyl -bromoiso-
butyrate and 0.1 mol of cyclohexanecarbonyl chloride.
The mixture was boiled for 1 h, decanted, and hydro-
lyzed with water. The organic layer was separated,
dried on calcined sodium sulfate, the solvent was
distilled off, and the reaction product was twice
distilled in a vacuum. Yield 51%, bp 134 135 C
(5 mm Hg), d240 1.0197, n2D0 1.4584. IR spectrum
Methyl 3-(1-bromocyclohexyl)-2,2-dimethyl-3-
oxopropanoate (IIIa). To a solution of 0.1 mol of
compound IIa in 25 ml of acetic acid was added at
stirring 0.11 mol of bromine. The mixture was heated
for 1.5 h on a water bath, then the solvent was
distilled off, and the reaction product was distilled in
1
1
( , cm ): 1730, 1750 (C=O). H NMR spectrum ( ,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001

SYNTHESIS OF 5-ARYL-2,2-DIMETHYL-4-OXASPIRO[5,5]UNDECANE-1,3-DIONES
813
a vacuum. Yield 68%, bp 162 164 C (11 mm Hg),
mp 62 63 C (from petroleum ether). IR spectrum
anhydrous ethyl ether, and 15 ml of anhydrous ethyl
acetate was added dropwise at stirring a mixture of
0.02 mol of methyl or ethyl 3-(1-bromocyclohexyl)-
2,2-dimethyl-3-oxopropanoate and 0.021 mol of an
appropriate aldehyde in 20 ml of a mixed solvent.
Then the reaction mixture was boiled for 1 h, cooled,
decanted, hydrolyzed with 5% hydrochloric acid, the
organic layer was separated, and from the water layer
the products were twice extracted with ether. The
combined organic solutions were dried with calcined
sodium sulfate, the solvents were distilled off, and the
final products VIIa g were twice recrystallized from
petroleum ether (bp 40 70 C) (see table).
1
( , cm ): 1715, 1730, 1760 (C=O). 1H NMR
spectrum ( , ppm): 0.73 2.16 m [10H, (CH2)5], 1.28
s (6H, CH3), 3.49 s (3H, OCH3). Found, %: C
49.35; H 6.49; Br 27.26. C12H19BrO3. Calculated,
%: C 49.50; H 6.58; Br 27.44.
Ethyl 3-(1-bromocyclohexyl)-2,2-dimethyl-3-
oxopropanoate (IIIb) was prepared in the same way
as compound IIIa starting with compound IIb. Yield
74%, bp 155 157 C (7 mm Hg), mp 36 38 C (from
1
petroleum ether). IR spectrum ( , cm ): 1715, 1730,
1
1760 (C=O). H NMR spectrum ( , ppm): 0.84 2.21
m [10H, (CH2)5], 1.09 t (3H, CH3CH2O), 1.29 s
(6H, CH3), 3.99 q (2H, OCH2 CH3). Found, %: C
51.01; H 6.96; Br 25.97. C13H21BrO3. Calculated,
%: C 51.16; H 6.94; Br 26.18.
REFERENCES
1. Shchepin, V.V. and Gladkova, G.E., Zh. Org. Khim.,
1995, vol. 31, no. 7, p. 1094.
2. Kirillov, N.F., Shchepin, V.V., and Litvinov, D.N.,
Zh. Org. Khim., 2000, vol. 36, no. 7, pp. 1010 1012.
5-R-2,2-dimethyl-4-oxaspiro[5,5]undecane-1,3-
diones (VIIa g). To a mixture of 6 g of fine zinc
turnings, catalytic amount of HgCl2, 10 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 6 2001