Synthesis of spiro- and dispirotetrahydropyrane-2,4-diones involving cyclobutane fragment in position 5 of heterocycle

Article abstract of DOI:10.1134/S1070363209080210

Methyl 3-(1-bromocyclobutyl)-2,2-dimethyl-3-oxopropanoates, 1-(1-bromocyclobutyl-carbonyl) cyclopentanoates and 1-(1- bromocyclobutylcarbonyl)cyclobutanoates react with zinc and aromatic aldehydes to form 5-aryl-8,8-dimethyl-6-oxaspiro[3.5]nonane-7,9-dion

Full text of DOI:10.1134/S1070363209080210

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 8, pp. 1707–1710. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © N.F. Kirillov, V.S. Melekhin, 2009, published in Zhurnal Obshchei Khimii, 2009, Vol. 79, No. 8, pp. 1347–1350.
Synthesis of Spiro- and Dispirotetrahydropyrane-2,4-diones
Involving Cyclobutane Fragment in Position 5 of Heterocycle
N. F. Kirillov and V. S. Melekhin
Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: kirillov@psu.ru
Received January 12, 2009
Abstract—Methyl 3-(1-bromocyclobutyl)-2,2-dimethyl-3-oxopropanoates, 1-(1-bromocyclobutyl-carbonyl)
cyclopentanoates and 1-(1-bromocyclobutylcarbonyl)cyclobutanoates react with zinc and aromatic aldehydes to
form 5-aryl-8,8-dimethyl-6-oxaspiro[3.5]nonane-7,9-diones, 13-aryl-12-oxadispiro[3.1.4.3]tridecane-5,11-diones
and 12-aryl-11-oxadispiro[3.1.3.3]dodecane-5,10-diones respectively.
DOI: 10.1134/S1070363209080210
Continuing previous studies on the synthesis of
some substituted tetrahydropyrane-2,4-diones contain-
ing spiro-carbon atom of four-membered ring in
position 3 of the heterocycle [1, 2], we synthesized
similar compounds with the same ring in the position 5
of the heterocycle.
Structure and composition of compounds obtained
were proved with elemental analysis, IR and Н NMR
1
spectra. In the IR spectra of aryltetrahydropyrane-2,4-
diones there are character-istic bands in the range of
1705–1710 and 1730–1745 cm–1 belonging to
carbonyls of ketone and lactone groups respectively.
1
In the Н NMR spectra a singlet signal appears at
Methyl 2,2-dimethyl-3-oxo-3-cyclobutylpropanoate
IV, 1-cyclobutylcarbonylcyclo-pentanoate V and 1-
cyclobutylcarbonylcyclobutanoate VI were synthe-
sized under the Reformatorskii reaction conditions
starting from methyl 2-bromo-2-methylpropanoate I,
1-bromocyclopentanoate II, and 1-bromocyclo-
butanoate III, zinc and cyclobutanoyl chloride. These
esters were converted by bromination into the key
bromo-derivatives: methyl 3-(1-bromocyclobutyl)-2,2-
dimethyl-3-oxopropanoate VII, 1-(1-bromocyclobutyl-
carbonyl)cyclo-pentanoate VIII and 1-(1-bromocyclo-
butylcarbonyl)cyclobutanoate IX. The bromo-deriv-
atives VII, VIII, and IX at reaction with zinc yield
zinc-enolates X, XI, and XII, which were added to
carbonyl group of aromatic aldehydes to give inter-
mediates XIIIа–XIIId, XIVа–XIVd and XVа–XVd.
Under the reaction conditions the latter transform
spontaneously into the target tetrahydropyrane-2,4-
diones containing trimethylene substituent in the
position 5 of heterocycle, namely, 5-aryl-8,8-dimethyl-
6-oxa-spiro[3.5]nonane-7,9-diones XVIа–XVId, 13-
aryl-12-oxadispiro[3.1.4.3]tridecane-5,11-diones XVIIа–
XVIId, and 12-aryl-11-oxadispiro[3.1.3.3]-dodecane-
5,10-dione XVIIIа–XVIIId (Scheme 1).
5.19–5.46 ppm, which is characteristic of methyne
proton.
EXPERIMENTAL
The IR spectra of compounds IV–IX and XVI–
XVIII were obtained on a Specord-75IR spectrometer
in mineral oil. The ¹Н NMR spectra (CDCl3) of
compounds IV–IX and XVIа–XVId were recorded on
a TESLA BS-567A spectrometer (100 МHz) and of
compounds XVIIа–XVIId and XVIIIа–XVIIId
(DMSO-d6), on a Mercury Plus-300 instrument
(300 МHz) internal to HMDS.
Methyl 2,2-dimethyl-3-oxo-3-cyclobutylpropano-
ate (IV). To a mixture of 10 g of powdered zinc in
25 ml of anhydrous benzene and 10 ml of anhydrous
ethyl acetate were added 0.1 mol of methyl 2-bromo-2-
methylpropanoate and 0.1 mol of cyclobutanoyl
chloride in 50 ml of benzene. This mixture was
refluxed for 1 h, decanted, and hydrolyzed with water.
Organic layer was separated, dried with anhydrous
sodium sulfate. Then solvents were removed and the
reaction product was twice distilled under a vacuum.
Yield 11.1 g (60 %), bp 97–98°С (10 mm Hg), d420
1707

1708
KIRILLOV, MELEKHIN
Scheme 1.
COCl
Br
Br2
Zn,
RR1CBrCOOMer
COCRR1COOMe
COCRR1COOMe
VII, VIII, IX
O
−HBr
−ZnBrCl
I, II, III
IV, V, VI
OZnBr
MeO
R1
CRR1COOMe
OZnBr
Ar
Zn
ArCHO
O
C
R
O
H
−MeOZnBr
R1
O
Ar
R
O
XVIа−XVId, XVIIa−XVIId,
XVIIIa−XVIIId
X, XI, XII
XIIIа−XIIId, XIVa−XIVd,
XVa−XVd
I, IV, VII, X, XIII, XVI: R = R1 = Me; II, V, VIII, XI, XIV, XVII: R + R1 = (CH2)4; III, VI, IX, XII, XV, XVIII: R + R1 =
(CH2)3. XIII, XVI: Ar = 4-BrC6H4 (а), 4-ClC6H4 (b), 2,4-Cl2C6H3 (c), 3-NO2C6H4 (d). XIV, XV, XVII, XVIII: Ar = 4-
BrC6H4 (а), 4-ClC6H4 (b), Ph (c), 4-МеОС6Н4 (d).
1
1.0243, nD20 1.4490. IR spectrum, ν, cm–1: 1705, 1725
(С=О). 1Н NMR spectrum, δ, ppm: 3.65 s (3Н, ОМе),
3.20–3.55 m (1Н, СНСО), 1.31 s (6Н, 2Ме), 1.70–
2.40 m [6Н, (СН2)3]. Found, %: С 65.01; Н 8.88.
С10Н16О3. Calculated, %: С 65.19; Н 8.75.
cm–1: 1710, 1735 (С=О). Н NMR spectrum, δ, ppm:
3.66 s (3Н, ОМе), 1.70–3.10 m [6Н, (СН2)3], 1.51 s
(6Н, 2Ме). Found, %: С 45.82; Н 5.65; Br 30.16.
С10Н15BrО3. Calculated, %: С 45.65; Н 5.75; Br 30.37.
Methyl 1-(1-bromocyclobutylcarbonyl)cyclopenta-
noate (VIII) was prepared similarly from compound
V. Yield 9.8 g (68%), bp 137–139°С (3 mm Hg), d420
1.3315, nD20 1.5051. IR spectrum, ν, cm–1: 1725, 1740
(С=О). 1Н NMR spectrum, δ, ppm: 3.70 s (3Н, ОМе),
1.60–3.03 m [14Н, (СН2)3, (СН2)4]. Found, %: С
50.08; Н 6.07; Br 27.31. С12Н17BrО3. Calculated, %: С
49.84; Н 5.93; Br 27.63.
Methyl 1-cyclobutylcarbonylcyclopentanoate (V)
was prepared similarly from methyl 1-bromocyclo-
pentanoate and cyclobutanoyl chloride. Yield 9.9 g
(47%), bp 157–159°С (28 mm Hg), d420 1.0555, nD20
1
1.4752. IR spectrum, ν, cm–1: 1710, 1725 (С=О). Н
NMR spectrum, δ, ppm: 3.64 с (3Н, ОМе), 3.16–3.49 m
(1Н, СНСО), 1.48–2.47 m [14Н, (СН2)3, (СН2)4].
Found, %: С 68.75; Н 8.51. С12Н18О3. Calculated, %:
С 68.54; Н 8.63.
Methyl 1-(1-bromocyclobutylcarbonyl)cyclobuta-
noate (IX) was prepared similarly from compound VI.
Yield 11.6 g (84%), bp 133–135°С (4 mm Hg), d420
1.3436, nD20 1.5002. IR spectrum, ν, cm–1: 1715, 1735
(С=О). 1Н NMR spectrum, δ, ppm: 3.73 s (3Н, ОМе),
1.80–3.15 m [12Н, (СН2)3, (СН2)3]. Found, %: С
48.21; Н 5.40; Br 29.29. С11Н15BrО3. Calculated, %: С
48.02; Н 5.50; Br 29.04.
Methyl 1-cyclobutylcarbonylcyclobutanoate (VI)
was prepared similarly from methyl 1-bromocyclo-
butanoate and cyclobytanoyl chloride. Yield, 12.8 g
(65%), bp 148–150°С (30 mm Hg), d420 1.0589, nD20
1
1.4707. IR spectrum, ν, cm–1: 1710, 1725 (С=О). Н
NMR spectrum, δ, ppm: 3.71 s (3Н, ОМе), 3.30–3.45 m
(1Н, СНСО), 1.77–2.55 m [12Н, (СН2)3, (СН2)3].
Found, %: С 67.51; Н 8.38. С11Н16О3. Calculated, %:
С 67.32; Н 8.22.
5-Aryl-8,8-dimethyl-6-oxaspiro[3.5]nonane-7,9-
diones (XVIа–XVId). To a mixture of 1 g of the fine
powdered zinc, catalytic amounts of mercuric chloride
and 30 ml of anhydrous ethyl acetate was dropwise
added a mixture of 10.5 mmol of compound VII and
10 mmol of the corresponding aldehyde in 15 ml of
anhydrous ethyl acetate under stirring (in preparing
XVId 3-nitrobenzaldehyde was added after heating for
0.5 h of compound VII with zinc). The reaction
mixture was refluxed for 2 h, cooled, separated from
zinc excess and hydrolyzed with 5% hydrochloric acid.
Methyl 3-(1-bromocyclobutyl)-2,2-dimethyl-3-
oxopropanoate (VII). To a solution of 0.05 mol of
compound IV in 20 ml of acetic acid was added
0.055 mol of bromine, and this mixture was heated for
1 h on a water bath. Then acetic acid was evaporated.
Bromine excess and reaction product were distilled
under a vacuum. Yield 9.3 g (71%), bp 120–122°С
(10 mm Hg), d420 1.3381, nD20 1.4806. IR spectrum, ν,
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SYNTHESIS OF SPIRO- AND DISPIROTETRAHYDROPYRANE-2,4-DIONES
1709
The organic layer was separated. The reaction products
were extracted with ethyl acetate from the water layer.
After drying this extract with anhydrous sodium
sulfate, ethyl acetate was evaporated, and compounds
XVIа–XVId were recrystalled from the methanol-
ethyl acetate mixture.
13-(4-Chlorophenyl)-12-oxadispiro[3.1.4.3]tride-
cane-5,11-dione (XVIIb). Yield 2.74 g (86%), mp
143–144°С. IR spectrum, ν, cm–1: 1710, 1740 (С=О).
1Н NMR spectrum, δ, ppm: 7.55 d, 7.49 d (4H, 4-
ClC6H4, J 8.4 Hz), 5.91 s (1Н, СНО), 1.13–2.48 m
[14Н, (СН2)3, (СН2)4]. Found, %: С 67.67; Н 5.89; Cl
11.30. С18Н19ClО3. Calculated, %: С 67.82; Н 6.01; Cl
11.12.
5-(4-Bromophenyl)-8,8-dimethyl-6-oxaspiro[3.5]-
nonane-7,9-dione (XVIа). Yield 3.03 g (90%), mp
145–146°С. IR spectrum, ν, cm–1: 1705, 1730 (С=О).
1Н NMR spectrum, δ, ppm: 7.45 d, 7.15 d (4Н, 4-
BrC6H4, J 8.3 Hz), 5.45 s (1Н, СНО), 1.65–2.57 m
[6Н, (СН2)3], 1.48 s (3Н, Ме), 1.24 s (3Н, Ме). Found,
%: С 57.05; Н 5.22; Br 23.89. С16Н17BrO3. Calculated,
%: С 56.99; Н 5.08; Br 23.70.
13-Phenyl-12-oxadispiro[3.1.4.3]tridecane-5,11-
dione (XVIIc). Yield 2.07 g (73%), mp 156–157°С.
1
IR spectrum, ν, cm–1: 1710, 1735 (С=О). Н NMR
spectrum, δ, ppm: 7.39–7.50 m (5H, Ph), 5.89 s (1Н,
СНО), 1.15–2.44 m [14Н, (СН2)3, (СН2)4]. Found, %:
С 76.21; Н 6.94. С18Н20О3. Calculated, %: С 76.03;
7.09.
8,8-Dimethyl-5-(4-chlorophenyl)-6-oxaspiro[3.5]-
nonane-7,9-dione (XVIb). Yield 2.55 g (87 %), mp
150–151°С. IR spectrum, ν, cm–1: 1720, 1745 (С=О).
1Н NMR spectrum, δ, ppm: 7.15–7.40 m (4H. 4-
ClC6H4), 5.48 s (1Н, СНО), 1.65–2.60 m [6Н, (СН2)3],
1.48 s (3Н, Ме), 1.24 s (3Н, Ме). Found, %: С 65.78;
Н 6.00; Cl 12.33. С16Н17ClО3. Calculated, %: С 65.64;
Н 5.85; Cl 12.11.
13-(4-Methoxyphenyl)-12-oxadispiro[3.1.4.3]tri-
decane-5,11-dione (XVIId). Yield 2.51 g (80%), mp
132–133°С. IR spectrum, ν, cm–1: 1705, 1735 (С=О).
1Н NMR spectrum, δ, ppm: 7.34 d, 7.02 d (4H. 4-
МеОC6H4, J 8.7 Hz), 5.83 s (1Н, СНО), 3.78 s (3H,
MeO), 1.12–2.42 m [14Н, (СН2)3, (СН2)4]. Found, %:
С 72.73; Н 7.13. С19Н22О4. Calculated, %: С 72.59;
7.05.
8,8-Dimethyl-5-(2,4-dichlorophenyl)-6-oxaspiro-
[3.5]nonane-7,9-dione (XVIc). Yield 2.26 g (69 %),
mp 76–77°С. IR spectrum, ν, cm–1: 1710, 1750 (С=О).
1Н NMR spectrum, δ, ppm: 7.59 d, 7.49 s, 7.40 d (3H,
2,4-Cl2C6H3, J 8.4 Hz), 5.92 s (1Н, СНО), 1.60–2.67
m [6Н, (СН2)3], 1.55 s (3Н, Ме), 1.51 s (3Н, Ме).
Found, %: С 58.88; Н 5.06; Cl 21.35. С16Н16Cl2О3.
Calculated, %: С 58.73; Н 4.93; Cl 21.67.
12-Aryl-11-oxadispiro[3.1.3.3]dodecane-5,10-di-
ones (XVIIIа–XVIIId) were prepared similarly from
bromooxoester IХ.
12-(4-Bromophenyl)-11-oxadispiro[3.1.3.3]dode-
cane-5,10-dione (XVIIIа). Yield 3.32 g (95%), mp
165–166°С. IR spectrum, ν, cm–1: 1705, 1730 (С=О).
1Н NMR spectrum, δ, ppm: 7.67 d, 7.39 d (4Н, 4-
BrC6H4, J 9.0 Hz), 5.73 s (1Н, СНО), 1.05–2.65 m
[12Н, (СН2)3, (СН2)3]. Found, %: С 58.67; Н 5.08; Br
23.07. С17Н17BrO3. Calculated, %: С 58.47; Н 4.91; Br
22.88.
8,8-Dimethyl-5-(3-nitrophenyl)-6-oxaspiro[3.5]-
nonane-7,9-dione (XVId). Yield 2.51 g (83 %), mp
170–171°С. IR spectrum, ν, cm–1: 1710, 1740 (С=О).
1Н NMR spectrum, δ, ppm: 7.45–8.26 m (4H, 3-
NO2C6H4), 5.57 s (1Н, СНО), 1.70–2.67 m [6Н, (СН2)3],
1.51 s (3Н, Ме), 1.35 s (3Н, Ме). Found, %: С 63.18;
Н 5.69; N 4.45. С16Н17NО5. Calculated, %: С 63.36; Н
5.65; N 4.62.
13-(4-Chlorophenyl)-12-oxadispiro[3.1.3.3]dode-
cane-5,11-dione (XVIIIb). Yield 2.75 g (90%), mp
158–159°С. IR spectrum, ν, cm–1: 1710, 1740 (С=О).
1Н NMR spectrum, δ, ppm: 7.54 d, 7.46 d (4H, 4-
ClC6H4, J 9.0 Hz), 5.75 s (1Н, СНО), 1.07–2.65 m
[12Н, (СН2)3, (СН2)3]. Found, %: С 67.21; Н 5.79; Cl
11.46. С17Н17ClО3. Calculated, %: С 67.00; Н 5.62; Cl
11.63.
13-Aryl-12-oxadispiro[3.1.4.3]tridecane-5,11-di-
ones (XVIIа–XVIId) were prepared similarly from
bromooxoester VIII.
13-(4-Bromophenyl)-12-oxadispiro[3.1.4.3]tride-
cane-5,11-dione (XVIIа). Yield 3.23 g (89%), mp
160–161°С. IR spectrum, ν, cm–1: 1715, 1745 (С=О).
1Н NMR spectrum, δ, ppm: 7.68 d, 7.42 d (4Н, 4-
BrC6H4, J 8.4 Hz), 5.90 s (1Н, СНО), 1.15–2.45 m
[14Н, (СН2)3, (СН2)4]. Found, %: С 59.70; Н 5.12; Br
21.79. С18Н19BrO3. Calculated, %: С59.52; Н 5.27; Br 22.00.
13-Phenyl-12-oxadispiro[3.1.3.3]dodecane-5,11-
dione (XVIIIc). Yield 2.21 g (82%), mp 151–152°С.
1
IR spectrum, ν, cm–1: 1710, 1740 (С=О). Н NMR
spectrum, δ, ppm: 7.37–7.49 m (5H, Ph), 5.74 s (1Н,
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KIRILLOV, MELEKHIN
СНО), 1.17-2.64 m [12Н, (СН2)3, (СН2)3]. Found, %:
С 75.38; Н 6.66. С17Н18О3. Calculated, %: С 75.53; 6.71.
ACKNOWLEDGMENTS
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 07-03-
96035).
13-(4-Methoxyphenyl)-12-oxadispiro[3.1.3.3]do-
decane-5,11-dione (XVIIId). Yield 2.61 g (87%), mp
130–131°С. IR spectrum, ν, cm–1: 1710, 1740 (С=О).
1Н NMR spectrum, δ, ppm: 7.30 d, 7.00 d (4H. 4-
МеОC6H4, J 9.0 Hz), 5.68 s (1Н, СНО), 1.20–2.60 m
[12Н, (СН2)3, (СН2)3]. Found, %: С 72.13; Н 6.58.
С18Н20О4. Calculated, %: С 71.98; 6.71.
REFERENCES
1. Shchepin, V.V., Kirillov, N.F., Melekhin, V.S., and
Vakhrin, M.I., Zh. Obshch. Khim., 2006, vol. 76, no. 10,
p. 1674.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 8 2009