Synthesis of dispirotetrahydropyran-2,4-diones containing six- and seven-membered rings

Article abstract of DOI:10.1134/S1070363209120159

Methyl 1-(1-bromocyclohexylcarbonyl)cycloheptane- and 1-(1- bromocycloheptylcarbonyl)cyclo- hexanecarboxylates react with zinc and aromatic aldehydes yielding 17-aryl-16-oxadispiro[5.1.6.3]hepta- decane-7,15-diones and 15-aryl-16-oxadispiro[5.1.6.3]heptad

Full text of DOI:10.1134/S1070363209120159

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 12, pp. 2652–2654. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.F. Kirillov, V.S. Melekhin, M.I. Vakhrin, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 12, pp. 2026–2028.
Synthesis of Dispirotetrahydropyran-2,4-diones
Containing Six- and Seven-Membered Rings
N. F. Kirillov, V. S. Melekhin, and M. I. Vakhrin
Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: kirillov@psu.ru
Received May 12, 2009
Abstract—Methyl 1-(1-bromocyclohexylcarbonyl)cycloheptane- and 1-(1-bromocycloheptylcarbonyl)cyclo-
hexanecarboxylates react with zinc and aromatic aldehydes yielding 17-aryl-16-oxadispiro[5.1.6.3]hepta-
decane-7,15-diones and 15-aryl-16-oxadispiro[5.1.6.3]heptadecane-7,17-diones respectively.
DOI: 10.1134/S1070363209120159
Dispirotetrahydropyran-2,4-diones involving four-,
five- and six-membered rings were earlier obtained by
the Reformatorskii’s reaction [1-3]. We synthesized
dispirotetrahydropyran-2,4-diones containing six- and
seven-membered rings simultaneously. Reaction of
methyl 1-bromocycloheptanecarboxylate with zinc and
cyclohexanecarboxylic acid chloride gives rise to
methyl 1-cyclohexylcarbonylcycloheptanecarboxylate
I. Methyl 1-(1-bromocyclohexylcarbonyl)cycloheptane-
carboxylate II was produced, when compound I was
brominated in acetic acid. Reaction of II with zinc
yields bromozinc-enolate III, which was added to the
carbonyl group of aromatic aldehydes to give
bromozinc-alcoholates IVа–IVe. In the course of the
reaction the latter suffered a spontaneous ring closure
liberating bromozinc methylate and forming the sub-
stituted dispirotetrahydropyran-2,4-diones containing six-
and seven-membered rings, namely, 17-aryl-16-oxadi-
spiro[5.1.6.3]heptadecane-7,15-diones Vа–Ve (Scheme 1).
Similarly the reaction of methyl 1-bromocyclo-
hexanecarboxylate with zinc and the cycloheptane-
carboxylic acid chloride produces methyl 1-cyclo-
heptylcarbonylcyclohexanecarboxylate VI, the bro-
mination of which yields methyl 1-(1-bromo-cyclo-
heptylcarbonyl)cyclohexanecarboxylate VII. The latter
reacts with zinc to form bromozinc-enolate VIII,
which was added to the carbonyl group of aromatic
aldehydes yielding bromozincalcoholates IXа–IXd.
Their cyclization results in 15-aryl-16-oxadispiro-
[5.1.6.3]heptadecane-7,17-diones Xа–Xd (Scheme 2).
Yields of the reaction products are 63–93%. The
composition and the structure of compounds Vа–Ve
and Xа–Xd were confirmed by the elemental analysis
Scheme 1.
O
O
Zn,
COCl
Br
Br2
_HBr
Br
COOMe
_ZnBrCl
COOMe
COOMe
I
II
O
OZnBr
O
Zn
ArCHO
_MeOZnBr
Ar
COOMe
III
Ar
O
O
COOMe
IVа_IVe
OZnBr
Vа_Ve
IV, V: Ar = 4-BrC6H4 (а), 4-ClC6H4 (b), 3-NO2C6H4 (c), Ph (d), 4-МеОС6Н4 (e).
2652

SYNTHESIS OF DISPIROTETRAHYDROPYRAN-2,4-DIONES
2653
Scheme 2.
O
O
COCl
Zn,
Br2
Br
Br
_ZnBrCl
HBr
COOMe
COOMe
COOMe
VII
VI
O
OZnBr
O
Zn
ArCHO
_MeOZnBr
Ar
COOMe
Ar
O
O
COOMe
OZnBr
IXа_IXd
Xа_Xd
VIII
IX, X: Ar = 4-BrC6H4 (а), 4-ClC6H4 (b), 3-NO2C6H4 (c), 4-FC6H4 (d).
1
data, IR and Н NMR spectroscopy. The IR spectra
contain characteristic absorption bands of ketone
carbonyls in the range of 1705–1715 cm–1 and of
compound I in 20 ml of acetic acid was added
0.055 mol of bromine. This mixture was heated for 1 h
on a water bath. Then the acetic acid and excess
bromine were evaporated and the reaction product was
distilled in a vacuum. Yield 12.3 g (71%), mp 48–
lactone carbonyl groups at 1735–1750 cm–1. In the Н
NMR spectra there are characteristic singlet signals of
the methine protons at 5.08–5.81 ppm.
1
1
49ºС. IR spectrum, ν, cm–1: 1710, 1745 (С=О). Н
NMR spectrum, δ, ppm: 1.05–2.37 m [22Н, (СН2)5,
(СН2)6], 3.63 s (3Н, ОМе). Found, %: С 55.84; Н
7.17; Br 22.91. С16Н25BrО3. Calculated, %: С 55.66; Н
7.30; Br 23.14.
EXPERIMENTAL
The IR spectra of compounds I, II, Vа–Ve, VI, VII
and Xа-Xd were obtained on a Specord-75IR spectro-
1
photometer in mineral oil. The Н NMR spectra of
17-Aryl-16-oxadispiro[5.1.6.3]heptadecane-7,15-
diones (Vа–Ve). To a mixture of 1 g of the fine zinc
turnings, catalytic amount of mercury(II) chloride, and
30 ml of anhydrous ethyl acetate was dropwise added a
mixture of 10 mmol of compound II and 9.6 mmol of
the corresponding aldehyde in 15 ml of anhydrous
ethyl acetate under stirring. In the preparation of
compound Vc the 3-nitrobenzaldehyde was added after
heating compound II with zinc for 0.5 h. The reaction
mixture was refluxed for 2 h, cooled, decanted from
the excess zinc and hydrolyzed with 5% hydrochloric
acid. The organic layer was separated. The reaction
product was twice extracted from the water layer with
ethyl acetate and dried with anhydrous sodium sulfate.
Then ethyl acetate was removed and the product was
recrystalled from ethyl acetate.
compounds I, II, Vd, Ve, VI, VII, Xа–Xd (CDCl3)
and Vа–Vc (DMSO-d6) were registered on a TESLA
BS-576A spectrometer (100 MHz) relative to internal
TMS.
Methyl 1-cyclohexylcarbonylcycloheptanecarboxy-
late (I). To a mixture of 10 g of the fine zinc turnings
in 25 ml of anhydrous benzene and 10 ml of anhydrous
ethyl acetate were dropwise added 0.1 mol of methyl
1-bromocycloheptanecarboxylate and 0.1 mol of
chloroanhydride of cyclohexanecarbonyl chloride in
50 ml of ethyl acetate. This mixture was refluxed for
1 h, decanted from the excess zinc, and hydrolyzed
with water. The organic layer was separated and dried
with anhydrous sodium sulfate. Then the solvents were
evaporated and the reaction product was twice distilled
in a vacuum. Yield 11.2 g (42 %), mp 168–170ºС
(6 mm Hg), d420 1.0523, nD20 1.4881. IR spectrum, ν,
17-(4-Bromophenyl)-16-oxadispiro[5.1.6.3]hepta-
decane-7,15-dione (Vа). Yield 1.95 g (93%), mp 212–
1
cm–1: 1715, 1740 (С=О). Н NMR spectrum, δ, ppm:
1
213°С. IR spectrum, ν, cm–1: 1715, 1750 (С=О). Н
1.02–2.17 m [22Н, (СН2)5, (СН2)6], 2.30–2.65 m (1Н,
СНСО), 3.65 s (3Н, ОМе). Found, %: С 72.36; Н
9.68. С16Н26О3. Calculated, %: С 72.14; Н 9.84.
NMR spectrum, δ, ppm: 0.60–2.60 m [22Н, (СН2)5,
(СН2)6], 5.51 s (1Н, СНО), 7.26 d, 7.55 d (4Н, 4-
BrC6H4, J 8.3 Hz). Found, %: С 62.88; Н 6.57; Br
18.83. С22Н27BrO3. Calculated, %: С 63.01; Н 6.49; Br
19.05.
Methyl 1-(1-bromocyclohexylcaronyl)cycloheptane-
carboxylate (II). To a solution of 0.05 mol of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 12 2009

2654
KIRILLOV et al.
17-(4-Chlorphenyl)-16-oxadispiro[5.1.6.3]hepta-
15-Aryl-16-oxadispiro[5.1.6.3]heptadecane-7,17-
diones (Xа–Xd) were prepared similarly to com-
pounds V using compound VII as the starting material.
decane-7,15-dione (Vb). Yield 1.69 g (90%), mp 199–
1
200°С. IR spectrum, ν, cm–1: 1715, 1745 (С=О). Н
NMR spectrum, δ, ppm: 0.60–2.30 m [22Н, (СН2)5,
(СН2)6], 5.52 s (1Н, СНО), 7.30 d, 7.42 d (4Н, 4-
ClC6H4, J 8.4 Hz). Found, %: С 70.32; Н 7.40; Cl
9.28. С22Н27ClO3. Calculated, %: С 70.48; Н 7.26; Cl
9.46.
15-(4-Bromophenyl)-16-oxadispiro[5.1.6.3]-
heptadecane-7,17-dione (Xа). Yield 1.89 g (90%),
mp 199–200°С. IR spectrum, ν, cm–1: 1705, 1735
(С=О). 1Н NMR spectrum, δ, ppm: 0.80–2.40 m [22Н,
(СН2)5, (СН2)6], 5.20 s (1Н, СНО), 7.20 d, 7.43 d (4Н,
4-BrC6H4, J 8.3 Hz). Found, %: С 63.20; Н 6.54; Br
19.28. С22Н27BrO3. Calculated, %: С 63.01; Н 6.49; Br
19.05.
17-(3-Nitrophenyl)-16-oxadispiro[5.1.6.3]hepta-
decane-7,15-dione (Vc). Yield 1.60 g (83%), mp 193–
1
194°С. IR spectrum, ν, cm–1: 1715, 1740 (С=О). Н
NMR spectrum, δ, ppm: 0.60–2.60 m [22Н, (СН2)5,
(СН2)6], 5.81 s (1Н, СНО), 7.68 t, 7.72 d, 8.14 s, 8.20
d (4Н, 3-NO2C6H4, J 8 Hz). Found, %: С 68.42; Н
7.21; N 3.44. С22Н27NO5. Calculated, %: С 68.55; Н
7.06; N 3.63.
15-(4-Chlorophenyl)-16-oxadispiro[5.1.6.3]-
heptadecane-7,17-dione (Xb). Yield 1.63 g (87%),
mp 184–185°С. IR spectrum, ν, cm–1: 1715, 1745
(С=О). 1Н NMR spectrum, δ, ppm: 0.80–2.45 m [22Н,
(СН2)5, (СН2)6], 5.23 s (1Н, СНО), 7.32 d, 7.40 d (4Н,
4-ClC6H4, J 8.4 Hz). Found, %: С 70.54; Н 7.09; Cl
9.58. С22Н27ClO3. Calculated, %: С 70.48; Н 7.26; Cl
9.46.
17-(Phenyl)-16-oxadispiro[5.1.6.3]heptadecane-
7,15-diones (Vd). Yield 1.28 g (75%), mp 155–156°С.
1
IR spectrum, ν, cm–1: 1705, 1740 (С=О). Н NMR
spectrum, δ, ppm: 0.60–2.40 m [22Н, (СН2)5, (СН2)6],
5.13 s (1Н, СНО), 7.27 s (5Н, Ph). Found, %: С 77.39;
Н 8.20. С22Н28O3. Calculated, %: С 77.61; Н 8.29.
15-(3-Nitrophenyl)-16-oxadispiro[5.1.6.3]-
heptadecane-7,17-dione (Xc). Yield 1.21 g (63%), mp
112–113°С. IR spectrum, ν, cm–1: 1715, 1740 (С=О).
1Н NMR spectrum, δ, ppm: 0.80–2.50 m [22Н, (СН2)5,
(СН2)6], 5.37 s (1Н, СНО), 7.51 t, 7.74 d, 8.17 d, 8.20
s (4Н, 3-NO2C6H4, J 8.3 Hz). Found, %: С 68.36; Н
7.01; N 3.58. С22Н27NO5. Calculated, %: С 68.55; Н
7.06; N 3.63.
17-(4-Methoxyphenyl)-16-oxadispiro[5.1.6.3]-
heptadecane-7,15-dione (Ve). Yield 1.33 g (72%), mp
185–186°С. IR spectrum, ν, cm–1: 1705, 1735 (С=О).
1Н NMR spectrum, δ, ppm: 0.60–2.40 m [22Н, (СН2)5,
(СН2)6], 3.78 s (3Н, МеО), 5.08 s (1Н, СНО), 6.80 d,
7.15 d (4Н, МеОС6Н4, J 8.4 Hz). Found, %: С 74.69;
Н 8.29. С23Н30O4. Calculated, %: С 74.56; Н 8.16.
15-(4-Fluorophenyl)-16-oxadispiro[5.1.6.3]-
heptadecane-7,17-dione (Xd). Yield 1.34 g (75%),
mp 141–142°С. IR spectrum, ν, cm–1: 1705, 1735
(С=О). 1Н NMR spectrum, δ, ppm: 0.80–2.44 m [22Н,
(СН2)5, (СН2)6], 5.23 s (1Н, СНО), 6.99 t, 7.30 t (4Н,
4-FC6H4, J 8.4 Hz). Found, %: С 73.86; Н 7.71.
С22Н27FO3. Calculated, %: С 73.72; Н 7.59.
Methyl 1-cycloheptylcarbonylcyclohexanecarboxy-
late (VI) was prepared similarly to compound I from
methyl 1-bromocyclohexanecarboxylate and cyclo-
heptanecarbonyl chloride. Yield 12.3 g (46%), mp
171–174°С (10 mm Hg), d420 1.0557, nD20 1.4886. IR
spectrum, ν, cm–1: 1710, 1725 (С=О). 1Н NMR
spectrum, δ, ppm: 1.10–2.25 m [22Н, (СН2)5, (СН2)6],
2.60–2.90 m (1Н, СНСО), 3.67 s (3Н, ОМе). Found,
%: С 72.01; Н 9.95. С16Н26О3. Calculated, %: С 72.14;
Н 9.84.
ACKNOWLEDGMENTS
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 07-03-
96035).
Methyl
1-(1-bromocycloheptylcarbonyl)cyclo-
REFERENCES
hexanecarboxylate (VII) was prepared similarly to
compound II from compound IV. Yield 11.7 g (68%),
bp 195–197°С (9 mm Hg), d420 1.2745, nD20 1.5162. IR
spectrum, ν, cm–1: 1720, 1740 (С=О). 1Н NMR
spectrum, δ, ppm: 1.20–2.50 m [22Н, (СН2)5, (СН2)6],
3.64 s (3Н, ОМе). Found, %: С 55.92; Н 7.41; Br
23.40. С16Н25BrО3. Calculated, %: С 55.66; Н 7.30; Br
23.14.
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 12 2009