Synthesis of 6-aryl-3,3-dimethyl-5-phenyl-2,3,5,6-tetrahydropyran-2,4- diones

Article abstract of DOI:10.1007/s11176-005-0445-1

Zinc enolates obtained from methyl 4-bromo-2,2-dimethyl-3-oxo-4- phenylbutanoates and zinc react with aromatic aldehydes to form 6-aryl-3,3-dimethyl-5-phenyl-2,3,5,6-tetrahydropyran-2,4-diones as a single geometric isomer. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11176-005-0445-1

Russian Journal of General Chemistry, Vol. 75, No. 9, 2005, pp. 1455 1457. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 9, 2005,
pp. 1528 1530.
Original Russian Text Copyright
2005 by Shchepin, Russkikh, Sazhneva, Vakhrin.
Synthesis of 6-Aryl-3,3-dimethyl-5-phenyl-
2,3,5,6-tetrahydropyran-2,4-diones
V. V. Shchepin, N. Yu. Russkikh, Yu. Kh. Sazhneva, and M. I. Vakhrin
Perm State University, Perm, Russia
Received July 22, 2004
Abstract Zinc enolates obtained from methyl 4-bromo-2,2-dimethyl-3-oxo-4-phenylbutanoates and zinc
react with aromatic aldehydes to form 6-aryl-3,3-dimethyl-5-phenyl-2,3,5,6-tetrahydropyran-2,4-diones as a
single geometric isomer.
In view of the practical importance of substituted
2,3,5,6-tetrahydropyran-2,4-diones [1 3], as well as
the scarcity of information about 2,3,5,6-tetrahydro-
pyran-2,4-diones with a 5-phenyl-substituted heteriring
[3 5], we have developed a new synthetic approach
to such compounds. To this end, we first reacted
methyl -bromoisobutyrate with phenylacetyl chloride
with zinc in ether benzene, 1:2, to obtain methyl
4-phenyl-3-oxobutanoate (I) and then converted the
latter, without isolation, in CCl medium, to bromo
derivative II.
4
3
2
1
Zn, PhCH2COCl
Br2
BrCMe2COOMe
[PhCH2COCMe2COOMe]
PhCHBrCOCMe2COOMe
HBr
ZnBrCl
I
II
Further on methyl 4-bromo-2,2-dimethyl-4-
phenyl-3-oxobutanoate (II) was reacted with
zinc and aromatic aldehydes in ether ethyl acetate,
1:3.
OZnBr
O
O
O
Ph<
H<>>
Ph
Me
Me
O
ArCHO (IVa IVf)
Me
Me
Me
Me
>
Zn
<
Ph
Ar
>
<
II
H
MeOZnBr
H
Ar
O
BrZnO
OMe
O
OMe
III
Va Vf
IVa IVf
IV VI, Ar = Ph (a), 4-ClC6H4 (b), 2,4-Cl2C6H3 (c), 2-BrC6H4 (d), 4-BrC6H4 (e), 3-NO2C6H4 (f).
Zinc enolate III formed by the Reformatskii rea-
ction regioselectively reacted with aldehydes IVa IVf
to form intermediates Va Vf which then cyclized into
the target compounds, 6-aryl-3,3-dimethyl-5-phenyl-
2,3,5,6-tetrahydropyran-2,4-diones VIa VIf.
formed in steps, i.e. first bromo derivative II was
reacted with zinc to obtain zinc enolate III and then
the latter was mixed with aldehyde in the absence of
zinc.
The yields of the final products were 32 55%. The
The reaction with m-nitrobenzaldehyde was per-
structure of compounds VIa VIf was proved by
1070-3632/05/7509-1455 2005 Pleiades Publishing, Inc.

1456
SHCHEPIN et al.
1
elemental analysis and IR and H NMR spectroscopy.
The IR spectra contain characteristic absorption bands
These data suggest that the reaction products are
formed as a single geometric isomer. To assess the
preferred structure of this isomer, we performed
quantum-chemical calculations of the molecular
geometries of possible isomers by the MO LCAO
method in the MNDO PM3 approximation (MOPAC.
Ver. 6.0. Public).
1
at 1720 1730 and 1745 1765 cm from the ketone
and lactone carbonyls. The H NMR spectra of com-
1
pounds VIa VIf (see table) show characteristic
signals at 3.75 3.99 and 5.53 6.16 ppm from the HC5
and HC6 protons, respectively (JHC C H 10 11 Hz).
5
6
O
O
O
O
Me
Me
Me
Me
Me
Me
H
Ph
Ph
H
Ph
H
Me
Me
H
Ph
Ph
H
Ph
H
H
Ph
H
Ph
O
O
O
O
O
O
O
O
A
B
C
D
1
fH, kJ mol
Angle, deg
J, Hz
295.28
170.27
12.7
295.27
170.27
12.7
287.13
53.92
4.9
287.13
53.92
4.9
According to the calculations, the most stable are
structures A and B with a transoid position of the
phenyl groups. By the Karplus equation with But-
NMR spectra were measured for solutions of com-
pounds II and VIa VIf in CDCl3 on a Tesla BS-567A
instrument (100 MHz).
5
6
ner Bie parameters we calculated the JHC C H
contants, using the HC5C6H dihedral angles. Com-
Methyl 4-bromo-2,2-dimethyl-3-oxo-4-phenyl-
butanoate (II). A mixture of 0.2 mol of methyl
-bromoisobutyrate and 0.2 mol of phenylacetyl chlo-
ride was added to 25 g of finely cut zinc in 100 ml of
ether and 30 ml of ethyl acetate. The resulting mixture
was refluxed for 20 min, decanted from zinc, and
hydrolyzed with water. The organic layer was dried
with sodium sulfate, and the solvent was removed.
5
6
parison of the calculated JHC C H values with ex-
perimental shows that the synthesized compounds
have structures like A and B.
EXPERIMENTAL
The IR spectra were measured on a UR-20 spec-
trophotometer for individual compounds. The 1H
1
Yields, melting points, H NMR spectra, and elemental analyses of 6-aryl-3,3-dimethyl-5-phenyl-2,3,5,6-tetrahydropyran-
2,4-diones VIa VIf
Calculated,
1H NMR spectrum, , ppm (J, Hz)
CHPh CH CHPh
Found, %
%
mp, C
Formula
CMe2
R
C
H
C
H
VIa 32 129 130 1.44 s, 3.84d(J 10) 5.57d(J 10) 6.70 6.95 m 7.03 s (Ph) 77.46 6.10 C19H18O3
77.53 6.16
1.54 s
VIb 45 112 113 1.46 s, 3.75d(J 11) 5.54d(J 11) 6.71 6.94 m 7.00 7.10m 69.33 5.15 C19H17ClO3 69.41 5.21
1.55 s (4-ClC6H4)
VIc 55 138 140 1.49 s, 3.93d(J 11) 6.0d(J 11) 6.71 6.77 m 7.05 7.24m 62.73 4.37 C19H16Cl2O3 62.83 4.44
1.60 s
(2,4-Cl2
C6H3)
VId 40 123 125 1.49 s, 3.99d(J 11) 6.16d(J 11) 6.74 6.80 m 7.01 7.18m 61.09 4.55 C19H17BrO3 61.14 4.59
1.60 s (2-BrC6H4)
VIe 48 125 127 1.46 s, 3.76d(J 11) 5.53d(J 11) 6.69 6.79 m 6.79 7.24m 61.08 4.54 C19H17BrO3 61.14 4.59
1.56 s (2-BrC6H4)
VIf 50 161 162 1.48 s, 3.78d(J 11) 5.65d(J 11) 6.69 6.72 m 7.06 7.24m 67.17 5.00 C19H17NO5 67.25 5.05
1.59 s
(3-NO2C6H4)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 9 2005

SYNTHESIS OF 6-ARYL-3,3-DIMETHYL-5-PHENYL-2,3,5,6-TETRAHYDROPYRAN-2,4-DIONES
1457
The product was distilled in a vacuum; bp 130
140 (2 5) mm Hg, n2D0 0 1.5040. Bromine, 0.14 mol,
was added dropwise with stirring and heating on a
water bath to a solution of methyl 2,2-dimethyl-4-
phenyl-3-oxobutanoic acid in 50 ml of CCl4. The mix-
ture was heated on a water bath until HBr no longer
evolved. The solvent was removed by distillation, and
the reaction product was doubly crystallized from
tion. Further workup was performed as described for
compounds VIa VIe. The final product was purified
by double crystallization from petroleum ether and
CCl4.
ACKNOWLEDGMENTS
The work was financially supported by the Russian
Foundation for Basic Research (project nos. 04-03-
96036 and 04-03-97505).
1
CCl4. Yield 60%, mp 65 67 C. H NMR spectrum
(CDCl3), , ppm: 1.26 s, 1.43 s (6H, CMe2), 3.41 s
(3H, OMe), 5.58 s (1H, CH), 7.12 7.34 m (5H, Ph).
Found, %: C 52.10; H 5.01. C13H15BrO3. Calculated,
%: C 52.19; H 5.05.
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ether. The organic layer was washed to neutral, dried
with sodium sulfate, and the solvent was removed.
The final products were purified by double crystalliza-
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 9 2005