Synthesis of 6-aryltetrahydropyran-2,4-diones containing tetra- and pentamethylene substituents in the 3 and 5 positions of the heteroring

Article abstract of DOI:10.1023/B:RUGC.0000042430.44366.01

Methyl esters of 1-(1-bromocyclopentylcarbonyl)- and 1-(1- bromocyclohexylcarbonyl)cyclopentanecarboxylic or 1-(1-bromocyclopentylcarbonyl) cyclohexanecarboxylic acids react with zinc and aromatic aldehydes to form 14-aryl-13-oxadispiro[4.1.4.3]tetradecan

Full text of DOI:10.1023/B:RUGC.0000042430.44366.01

Russian Journal of General Chemistry, Vol. 74, No. 6, 2004, pp. 933 936. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 6, 2004,
pp. 1009 1012.
Original Russian Text Copyright
2004 by Shchepin, Kirillov, Vakhrin.
Synthesis of 6-Aryltetrahydropyran-2,4-diones
Containing Tetra- and Pentamethylene Substituents
in the 3 and 5 Positions of the Heteroring
V. V. Shchepin, N. F. Kirillov, and M. I. Vakhrin
Perm State University, Perm, Russia
Received June 4, 2002
Abstract Methyl esters of 1-(1-bromocyclopentylcarbonyl)- and 1-(1-bromocyclohexylcarbonyl)cyclo-
pentanecarboxylic or 1-(1-bromocyclopentylcarbonyl)cyclohexanecarboxylic acids react with zinc and
aromatic aldehydes to form 14-aryl-13-oxadispiro[4.1.4.3]tetradecane-6,12-diones, 13-aryl-14-oxadispiro-
[4.1.5.3]pentadecane-6,15-diones, and 15-aryl-14-oxadispiro[4.1.5.3]pentadecane-6,13-diones, respectively.
Proceeding with our research on the synthesis of
substituted tetrahydropyran-2,4-diones with spiro
carbon atoms in the 3 and 5 positions of the hetero-
ring [1], we developed synthetic procedures for related
compounds with tetra- and pentamethylene substi-
tuents in the mentioned positions. Under Reformatskii
reaction conditions, starting from methyl 1-bromo-
cyclopentanecarboxylate (I), zinc, and cyclopentyl-
carbonyl chloride, we prepared methyl 1-(cyclopentyl-
carbonyl)cyclopentanecarboxylate (II). The latter was
brominated to obtain a key bromo derivative, methyl
1-(1-bromocyclopentylcarbonyl)cyclopentanecar-
boxylate (III). Bromo derivative III was reacted with
zinc and aromatic aldehydes. The reaction involved
addition of intermediate zinc enolate IV to the car-
bonyl group of the aldehyde, yielding intermediate V
which spontaneously converted into the target pyran-
2,4-diones with two tetramethylene substituents in the
3 and 5 positions of the heteroring, namely, 14-aryl-
13-oxadispiro[4.1.4.3]tetradecane-6,12-diones VIa
and VIb, by the following scheme.
O
O
COCl
Zn,
Br
Br2
H
O
Br
O
HBr
ZnBrCl
O
O
Me
O
O
Me
Me
I
II
III
O
OZnBr
O
Ar
H
ArCH=O
Ar
H
MeOZnBr
O
O
O
O
O
Me
O
BrZn Me
Va, Vb
V, VI, Ar = Ph (a), 4-BrC6H4 (b).
O
Me
IV
VIa, VIb
In a similar way, from bromo derivative I, zinc,
and cyclohexylcarbonyl chloride we prepared methyl
1-(cyclohexylcarbonyl)cyclopentanecarboxylate (VII)
whose subsequent bromination gave bromo derivative
VIII. The latter was reacted with bromo derivative
VIII, zinc, and aromatic aldehydes to obtain 13-aryl-
14-oxadispiro[4.1.5.3]pentadecane-6,15-diones IXa
IXc by the following scheme.
1070-3632/04/7406-0933 2004 MAIK Nauka/Interperiodica

934
SHCHEPIN et al.
O
O
O
O
COCl
Zn,
Br2
Zn, ArCH=O
MeOZnBr
Ar
H
I
H
Br
HBr
ZnBrCl
O
O
O
Me
Me
O
O
VII
VIII
IXa IXc
IX, Ar = Ph (a), 4-BrC6H4 (b), 3-NO2C6H4 (c).
In a similar way, from methyl 1-bromocyclohexa-
necarboxylate (X), zinc, and cyclopentylcarbonyl
chloride we synthesized methyl 1-(cyclopentylcar-
bonyl)cyclohexanecarboxylate (XI) and brominated it
to obtain compound XII. The Reformatskii reaction
of the latter with zinc and aromatic aldehydes gave
15-aryl-14-oxadispiro[4.1.5.3]pentadecane-6,13-di-
ones XIIIa XIIIc by the following scheme.
O
Br
Zn,
COCl
O
H
ZnBrCl
O
Me
O
Me
O
X
XI
O
O
O
Zn, ArCH=O
MeOZnBr
Br2
HBr
Ar
H
Br
O
O
Me
O
XII
XIIIa XIIIc
XIII, Ar = Ph (a), 4-BrC6H4 (b), 3-NO2C6H4 (c).
The composition and structure of compounds VIa,
VIb, IXa IXc, and XIIIa XIIIc were proved by
Methyl 1-(cyclopentylcarbonyl)cyclopentane-
carboxylate (II). A solution of 0.1 mol of methyl
1-bromocyclopentanecarboxylate and 0.1 mol of
cyclopentylcarbonyl chloride in 50 ml of anhydrous
benzene was added dropwise to 10 g of fine zinc
turnings in 10 ml of anhydrous ethyl acetate. The
mixture was refluxed for 1 h, decanted from excess
zinc, and hydrolyzed with water. The organic layer
was dried with sodium sulfate, the solvent was
removed by distillation, and the reaction product was
distilled in a vacuum, yield 62%, bp 137 139 C
(7 mm Hg), d240 1.0726, n2D0 1.4782. IR spectrum, ,
1
elemental analysis and H NMR and IR spectroscopy
1
(see table). The H NMR spectra of the synthesized
compounds contain a methine proton signal at 5.15
5.77 ppm. The IR spectra display characteristic absor-
1
ption bands at 1715 1720 and 1745 1750 cm ,
belonging to the ketone and lactone carbonyl groups,
respectively.
EXPERIMENTAL
The 1H NMR spectra were recorded in CDCl3 (VIb,
IXa, IXb) or CCl4 solutions (IXc, with DMSO-d6
addition] on an RYa-2310 spectrometer (60 MHz),
internal reference HMDS. The IR spectra were
measured on a UR-20 spectrophotometer in mineral
oil.
1
1
cm : 1720, 1740 (C=O). H NMR spectrum, , ppm:
3.62 s (3H, OCH3), 2.50 2.95 m (1H, CHCO), 1.10
2.20
m (16H, cyclopentane ring). Found, %:
C 69.48; H 9.08. C13H20O3. Calculated, %: C 69.61;
H 8.99.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

SYNTHESIS OF 6-ARYLTETRAHYDROPYRAN-2,4-DIONES
935
1
Yields, melting points, IR spectra, H NMR spectra, and elemental analyses of 6-aryltetrahydropyran-2,4-diones IVa,
IVb, IXa IXc, and XIIIa XIIIc
IR spec-
trum,
, cm
1H NMR spectrum, , ppm
Found, %
Calculated, %
1
mp,
C
Formula
Br
(N)
Br
(N)
a
Ar
CHO
C
H
C
H
VIa
VIb
54 156 157 1715 1745
44 166 167 1715 1745
7.35 s
(5H ,Ph)
7.25 d,
7.55 d
5.38 s 0.70 2.35 76.29 7.41
(1H) (16H)
5.44 s 0.65 2.45 60.31 5.55 20.95 C19H21BrO3 60.49 5.61 21.18
(1H) (16H)
C19H22O3
76.48 7.43
(4H,
4-BrC6H4)
7.29 s
(5H, Ph)
7.14 d,
7.52 d
IXa
IXb
75 163 164 1715 1745
67 172 173 1715 1745
5.18 s 0.65 2.45 76.73 7.59
(1H) (18H)
5.15 s 0.75 2.35 61.45 5.84 20.36 C20H23BrO3 61.39 5.92 20.42
(1H) (18H)
C20H24O3
76.89 7.74
(4H,
4-BrC6H4)
7.60
7.83 m,
8.10 8.25m
(4H,
IXc
48 164 166 1715 1750
5.77 s 0.65 2.25 67.05 6.62 (3.74) C20H23NO5 67.21 6.49 (3.92)
(1H) (18H)
3-NO2C6H4)
7.32 s
(5H, Ph)
7.32 d,
7.43 d
XIIIa 75 138 139 1715 1745
XIIIb 68 172 173 1715 1745
XIIIc 54 144 145 1720 1750
5.39 s 0.90 2.30 76.75 7.79
(1H) (18H)
5.37 s 0.90 2.25 61.21 5.83 20.20 C20H23BrO3 61.39 5.92 20.42
5.37 s
C20H24O3
76.89 7.74
7.55
5.57 s 0.75 2.40 67.35 6.32 (3.85) C20H23NO5 67.21 6.49 (3.92)
7.85 m,
8.05 8.25m
(4H,
(1H)
(18H)
3-NO2C6H4)
a
Cyclohexane and cyclopentane rings.
Methyl 1-(cyclohexylcarbonyl)cyclopentane-
carboxylate (VII) was prepared similarly to com-
pound II, starting from methyl 1-bromocyclopentane-
carboxylate and cyclohexylcarbonyl chloride, yield
69%, bp 159 162 C (12 mm Hg), d240 1.0563, nD20
II, starting from methyl 1-bromocyclohexane car-
boxylate and cyclopentylcarbonyl chloride, yield 58%,
bp 162 164 C (14 mm Hg), d240 1.0625, nD20 1.4823.
1
1
IR spectrum, , cm : 1715, 1730, 1745 (C=O). H
NMR spectrum, , ppm: 3.60 s (3H, OCH3), 2.65
3.05 m (1H, CHCO), 1.00 2.10 m (18H, cyclopentane
and cyclohexane rings). Found, %: C 70.49; H 9.23.
C14H22O3. Calculated, %: C 70.56; H 9.30.
1
1.4802. IR spectrum, , cm : 1720, 1735, 1750
1
(C=O). H NMR spectrum, , ppm: 3.60 s (3H, OCH3),
2.55 3.00 m (1H, CHCO), 1.00 2.50 m (18H, cyclo-
pentane and cyclohexane rings). Found, %: C 70.72;
H 9.25. C14H22O3. Calculated, %: C 70.56; H 9.30.
Methyl 1-(1-bromocyclopentylcarbonyl)cyclo-
pentanecarboxylate (III). Bromine, 0.11 mol, was
added to a stirred solution of 0.1 mol of compound II
in 25 ml of acetic acid. The mixture was heated for
Methyl 1-(cyclopentylcarbonyl)cyclohexane-
carboxylate (XI) was prepared similarly to compound
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004

936
SHCHEPIN et al.
1.5 h on a water bath, excess bromine was removed
by distillation, and the reaction product was distilled
in a vacuum, yield 77%, bp 159 162 C (6 mm Hg),
wise to a stirred mixture of 3 g of fine zinc turnings, a
catalytic amount of mercuric chloride, and 30 ml of
the same solvent. The reaction mixture was refluxed
for 1 h, cooled, decanted from excess zinc, and
hydrolyzed with 5% HCl. The organic layer was se-
parated, and the aqueous layer was treated with two
portions of ethyl acetate. The extract was dried with
sodium sulfate, the solvent was removed by distilla-
tion, and compounds VIa, VIb were reacrystallized
from ethyl acetate.
d240 1.3508, n2D0 1.5086. IR spectrum, , cm : 1725,
1
1
1755 (C=O). H NMR spectrum, , ppm: 3.60 s (3H,
OCH3), 1.10 2.35 m (16H, cyclopentane ring).
Found, %: C 51.38; H 6.25; Br 26.48. C13H19BrO3.
Calculated, %: C 51.50; H 6.32; Br 26.35.
Methyl 1-(1-bromocyclohexylcarbonyl)cyclo-
pentanecarboxylate (VIII) was prepared similarly to
compound III, starting from compound VII. The re-
action product was twice recrystallized from petro-
leum ether (bp 40 70 C), yield 61%, mp 62 63 C.
13-Aryl-14-oxadispiro[4.1.5.3]pentadecane-6,15-
diones IXa IXc. Compounds IXa, IXb were pre-
pared similarly to compounds VI, starting from com-
pound VIII. Compound IXc was prepared as follows.
Compound VIII, 0.02 mol, in 15 ml of anhydrous
ethyl acetate was added dropwise to a stirred mixture
of 3 g of fine zinc turnings, a catalytic amount of
mercuric chloride, and 30 ml of anhydrous ethyl
acetate. The reaction mixture was refluxed for 0.5 h,
cooled, a solution of 0.017 mol of 3-nitrobenzal-
dehyde in 15 ml of ethyl acetate was added, and then
the reaction was performed as described for com-
pounds VI.
1
1
IR spectrum, , cm : 1715, 1730, 1755 (C=O). H
NMR spectrum, , ppm: 3.60 s (3H, OCH3), 1.00
2.50 m (18H, cyclopentane and cyclohexane ring).
Found, %: C 52.96; H 6.51; Br 25.25. C14H21BrO3.
Calculated, %: C 53.01; H 6.67; Br 25.19.
Methyl 1-(1-bromocyclopentylcarbonyl)cyclo-
hexanecarboxylate (XII) was prepared similarly to
compound III, starting from compound XI, yield 86%,
bp 163 166 C (4 mm Hg), d240 1.3369, nD20 1.5143. IR
1
1
spectrum, , cm : 1720, 1735, 1755 (C=O). H NMR
spectrum, , ppm: 3.61s (3H, OCH3), 1.00 2.45 m
(18H, cyclopentane and cyclohexane rings). Found,
%: C 52.92; H 6.50; Br 25.01. C14H21BrO3. Cal-
culated, %: C 53.01; H 6.67; Br 25.19.
15-Aryl-14-oxadispiro[4.1.5.3]pentadecane-6,13-
diones XIIIa XIIIc. Compounds XIIIa, XIIIb
were prepared similarly to compound VI, and com-
pound XIIIc, similarly to compound IXc, starting
from compound XII.
14-Aryl-13-oxadispiro[4.1.4.3]tetradecane-6,12-
diones VIa, VIb. A solution of 0.02 mol of com-
pound III and 0.017 mol of corresponding aldehyde
in 30 ml of anhydrous ethyl acetate was added drop-
REFERENCES
1. Kirillov, N.F. and Shchepin, V.V., Zh. Org. Khim.,
2001, vol. 37, no. 9, p. 1290.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 6 2004