Reaction of Zinc and Sodium Enolates of 3-Alkyl-6-aryl-5,5-dimethyl-2,3,5, 6-tetrahydropyrane-2,4-diones with Acyl Chlorides or Benzyl Bromides

Article abstract of DOI:10.1023/A:1026191021119

Zinc enolates of 3-alkyl-6-aryl-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4- diones react with acyl chlorides to form O-acylation products, 4-acyloxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-dihydropyrane-2-ones. Sodium enolates of these pyranediones react in DMSO w

Full text of DOI:10.1023/A:1026191021119

Russian Journal of General Chemistry, Vol. 73, No. 5, 2003, pp. 760 764. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 5, 2003,
pp. 804 808.
Original Russian Text Copyright
2003 by Shchepin, Sazhneva, Russkikh, Vakhrin.
Reaction of Zinc and Sodium Enolates
of 3-Alkyl-6-aryl-5,5-dimethyl-2,3,5,6-tetrahydropyrane-
2,4-diones with Acyl Chlorides or Benzyl Bromides
V. V. Shchepin, Yu. Kh. Sazhneva, N. Yu. Russkikh, and M. I. Vakhrin
Perm State University, Perm, Russia
Received April 18, 2001
Abstract Zinc enolates of 3-alkyl-6-aryl-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4-diones react with acyl
chlorides to form O-acylation products, 4-acyloxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-dihydropyrane-2-ones.
Sodium enolates of these pyranediones react in DMSO with substituted benzyl bromides to give mainly
C-alkylation products, 3-alkyl-6-aryl-3-(4-R-benzyl)-5,5-dimethyl-2,3,5,6-tetrahydropyrane-2,4-diones, as
single geometric isomers. In some cases, O-alkylation products, 4-alkoxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-di-
hydropyrane-2-ones, are formed as by-products ( 10 15%).
Earlier we found that ethyl 2,4-dibromo-2,4-di-
methyl-3-oxopentanoate reacts with zinc and aromatic
aldehydes to form mainly 6-aryl-3,5,5-trimethyl-2,3,
5,6-tetrahydropyrane-2,4-diones [1]. In that com-
munication we also suggested that the reaction results
in formation of zinc enolates of 6-aryl-5,5-dimethyl-3-
R-2,3,5,6-tetrahydropyrane-2,4-diones I which hyd-
rolize to give the final products, pyranediones II.
To substantiate this suggestion, as well as to extend
synthetic possibilities of the mentioned reaction, we
studied the reaction of zinc enolates I with acyl
chlorides and substituted benzyl bromides (Scheme 1).
The reaction of zinc enolate of 3,5,5-trimethyl-6-
phenyl-2,3,5,6-tetrahydropyrane-2,4-dione (Ia) with
succinyl chloride proceeds similarly to give bis(3,5,5-
trimethyl-6-phenyl-2-oxo-5,6-dihydropyran-4-yl) suc-
cinate (V).
On addition of acyl chlorides to the postreaction
mixture we isolated 4-acyloxy-3-alkyl-6-aryl-5,5-di-
methyl-5,6-dihydropyrane-2,4-diones IIIa IIIj
(Table 1) formed by O-acylation of zinc enolates I.
The yields of compounds IIIa IIIj are 37 80%.
Their composition and structure were proved by
1
elemental analysis and H NMR and IR spectroscopy.
The IR spectra contain characteristic absorption bands
1
at 1730 1770 cm and an absorption band of the
Alternative compounds IV, the products of C-acyla-
tion of zinc enolates I, were not found. Similar regio-
specific O-acylation was earlier observed in the reac-
tion of acyl chlorides with intermediately formed zinc
enolates of 2-alkyl-3-oxoalkanoates [2, 3].
1
double bond at 1670 1680 cm . The 1H NMR spectra
show typical singlet signals at 0.77 1.05, 1.57 1.70,
and 5.10 5.53 ppm, belonging to methyl (Me2C,
MeC) and methine (CHO) protons, respectively.
1070-3632/03/7305-0760$25.00 2003 MAIK Nauka/Interperiodica

REACTON OF ZINC AND SODIUM ENOLATES
761
Scheme 1.
I, R1 = Me; R2 = Ph (a), 4-BrC6H4 (b), 4-ClC6H4 (c), 3,4-(MeO)2C6H3 (d). I, R1 = Et; R2 = Ph (e). III, R1 = Me, R2 = Ph;
R3 = Me (a), t-Bu (b), Ph (c), 4-BrC6H4 (d). III, R1 = Me, R2 = 4-BrC6H4; R3 = Me (e), Ph (f); III, R1 = Me, R2 =
4-ClC6H4; R3 = Ph (g), 4-BrC6H4 (h). III, R1 = Me, R2 = 3,4-(MeO)2C6H3, R3 = Ph (i). III, R1 = Et, R2 = R3 = Ph (j).
Attempted reaction zinc enolate I with substituted
benzyl bromides failed. For this reason, we converted
intermediate I it into a more nucleophilically active
sodium enolate VI (Scheme 2).
VI is formed both from pyranediones II and from
their acyl derivatives III. This result is yet another
evidence that the acylation of zinc enolate I with acyl
chlorides involves attack of zinc enolate I on the
O-nucleophilic center.
As seen from the above scheme, sodium enolate
1
Table 1. Yields, constants, H NMR spectra (in DMSO-d6), and elemental analyses of 4-acyloxy-3-alkyl-6-aryl-5,5-di-
methyl-5,6-dihydropyrane-2-ones IIIa IIIj
bp,
(p, mm)
or mp,
C
1H NMR spectrum, , ppm
Comp. Yield,
no.
%
C
CMe2
H
R1
R2
R3
2.12 s (Me)
IIIaa
IIIb
IIIc
IIId
IIIe
37
40
79
73
65
188 190 (6) 0.77 s
5.10 s 1.57 s (Me)
7.18 s (Ph)
7.40 s (Ph)
7.43 s (Ph)
7.43 s (Ph)
7.35 d, 7.60 d
(4-BrC6H4)
113 116
176 177
155 156
128 129
0.92 s, 0.97 s 5.40 s 1.63 s (Me)
1.02 s, 1.05 s 5.50 s 1.70 s (Me)
1.03 s, 1.05 s 5.50 s 1.70 s (Me)
0.87 s, 0.97 s 5.40 s 1.67 s (Me)
1.33 s (t-Bu)
7.62 t, 7.77 t, 8.12 d (Ph)
7.83 d, 8.05 d (4-BrC6H4)
2.30 s (Me)
IIIf
80
159 160
1.00 s, 1.05 s 5.48 s 1.70 s (Me)
7.40 d, 7.58 d
7.60 t, 7.75 t, 8.10 d (Ph)
(4-BrC6H4)
IIIg
IIIh
IIIi
84
67
59
187 188
160 161
149 150
1.00 s, 1.05s 5.53 s 1.70 s (Me)
1.00 s, 1.03 s 5.53 s 1.70 s (Me)
7.47 s (4-ClC6H4) 7.63 t, 7.77 t, 8.12 d (Ph)
7.46 s (Ph)
7.81 d, 8.03 d (4-BrC6H4)
7.63 t, 7.76 t, 8.12 d (Ph)
1.05 s
5.40 s 1.70 s (Me)
6.96 s, 7.00 s
[3,4-(MeO)2C6H3]
IIIj
78
163 164
1.03 s
5.47 s 1.02 t, 2.12 d.q, 7.43 s (Ph)
7.63 t, 7.77 t, 8.11 d (Ph)
2.22 d.q (Et)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

762
SHCHEPIN et al.
Scheme 2.
II, R1 = Me, R2 = Ph (a, b), 4-BrC6H4 (c). VI, R1 = Me, R2 = Ph (a, b), 4-BrC6H4 (c), 4-ClC6H4 (d). VII, R1 = Me, R2 =
Ph, R4 = Br (d), NO2 (b); R2 = 4-BrC6H4, R4 = Br (c); R2 = 4-ClC6H4, R4 = Br (d). VIII, R1 = Me, R2 = Ph, R4 = Br
(a); R2 = 4-BrC6H4, R4 = Br (b).
Table 1. (Contd.)
kyl-6-aryl-4-(4-R4-benzyloxy)-5,5-dimethyl-5,6-di-
hydropyran-2-ones (VIIIa, VIIIb). Thus, in the H
1
Found, %
Calculated, %
NMR spectrum of compound VIIa we observed, along
with signals of the major product, signals belonging
to the O-alkylation product, , ppm: 0.90 s, 1.03 s
(CMe2), 2.00 s (Me), 5.03 s (CHO), and 4.87 and
5.23 d.d (CH2). By recrystallization of 3-(4-bromo-
benzyl)-3,5,5-trimethyl-6-phenyl-2,3,5,6-tetrahydro-
pyrane-2,4-dione (VIIa) containing 15% of 4-(4-
bromobenzoyloxy)-3,5,5-trimethyl-6-phenyl-5,6-di-
hydropyran-2-one (VIIIa) from acetone we were able
to separate these two compounds. First compound
VIIIa was isolated, 174 175 C, and then, after eva-
poration of most acetone, pure compound VIIa, mp
119 120 C. The IR spectrum of compound VIIIa
displayed typical absorption bands of the double bond
Comp.
no.
Formula
C
H
C
H
IIIaa 69.91
6.42 C16H18O4
7.50 C19H24O4
5.88 C21H20O4
4.47 C21H19BrO4
4.75 C16H17BrO4
4.52 C21H19BrO4
5.06 C21H19ClO4
3.93 C21H18BrClO4 56.06
6.00 C23H24O6
6.19 C22H22O4
70.07
72.15
75.00
60.72
65.39
60.72
68.02
6.57
7.59
5.95
4.58
4.82
4.58
5.13
4.00
6.06
6.29
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
72.00
74.85
60.52
65.22
60.60
57.85
55.91
69.56
75.20
69.67
75.43
IIIj
1
1
(1640 cm ) and the carbonyl group (1720 cm ).
a
In CCl .
4
It should be noted that C-alkylation products
VIIa VIId are formed as single geometric isomers.
Their IR spectra show characteristic carbonyl absorp-
Sodium enolate VI was reacted with para-sub-
stituted benzyl bromides both in methanol (method a)
and DMSO (method b). It was found that both reac-
tions give mainly C-alkylation products, 3-alkyl-6-
aryl-3-(4-R4-benzyl)-5,5-dimethyl-2,3,5,6-tetrahydro-
pyrane-2,4-diones VIIa VIId in yields of 9 12%
(in MeOH) and 50 68% (in DMSO) (Table 2).
1
tion bands at 1715 1760 cm .
The reaction of sodium enolate VIa and , -di-
bromo-p-xylene in methanol gave , -di(3,5,5-tri-
methyl-6-phenyl-2,4-dioxo-2,3,5,6-tetrahydropyran-3-
yl)-p-xylene (IX) as a single geometric isomer, mp
275 276 C (Scheme 3).
Compounds VIIb and VIId contained no admix-
1
tures of O-alkylation products. Their H NMR spectra
displayed typical singlet signals at 0.67 0.93, 1.53,
and 3.38 3.73 ppm, belonging to methyl (Me2C, Me)
and methine protons, respectively, and a doublet at
2.98 3.47 ppm from methylene protons.
Similar reaction of sodium enolate VIa with , -
dibromo-p-xylene in DMSO resulted in isolation of
two products with different melting points (195 196
and 275 276 C). The different chemical shifts, spe-
cifically of the CHO proton ( , ppm: 3.57 s and 3.87 s,
Compounds VIIa and VIIc were found to contain
10 15% admixtures of O-alkylation products, 3-al-
1
respectively) in the H NMR spectra of these two
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

REACTON OF ZINC AND SODIUM ENOLATES
763
Scheme 3.
Table 2. Yields, constants, 1H NMR spectra, and elemental analyses of 3-alkyl-6-aryl-3-(4-R4-benzyl)-5,5-dimethyl-
2,3,5,6-tetrahydropyrane-2,4-diones (VIIa VIId)
1H NMR spectrum, , ppm
Comp. Yield,
mp,
C
Solvent
no.
%
(solvent)
CMe2
CH
R1
R2
CH2 (4-R4C6H4)
VIIa
VIIb
VIIca
VIId
50
68
119 120
(acetone)
170 173
0.68 s, 3.47 s 1.53 s 7.33 s (Ph)
0.90 s (Me)
0.70 s, 3.73 s 1.53 s 6.80 7.48 ·
(Me) (Ph)
0.85 s, 4.60 s 1.41 s 7.15 d, 7.55 d 2.93 d, 3.35 d (CH2, J 12 Hz), DMSO-d6
0.93 s (Me) (4-BrC6H4) 7.05 d, 7.49 d (4-BrC6H4)
0.67 s, 3.38 s 1.53 s 6.97 d, 7.23 d 2.98 d, 3.32 d (CH2, J 12 Hz), CDCl3
0.87 s (Me) (4-ClC6H4) 6.85 d, 7.40 d (4-BrC6H4)
2.98 d, 3.33 d (CH2, J 12 Hz), CDCl3
7.00 d, 7.43 d (4-BrC6H4)
3.07 d, 3.47 d (CH2, J 12 Hz), CDCl3
7.30 d, 8.13 d (4-NO2C6H4)
(acetonitrile) 0.93 s
12,b 62
9,b 57
141 142
(acetone)
140 141
(methanol)
Table 2. (Contd.)
ments, and for CCl4 and CDCl3 on an RYa-2310
(60 MHz) spectrometer (III, VIIa VIIc, VIII, IX).
Found, %
Calculated, %
Comp.
no.
4-Acyloxy-3-alkyl-6-aryl-5,5-dimethyl-5,6-di-
hydropyran-2-ones IIIa IIIj. To 10 g of finely
chipped zinc, catalytic amounts of mercuric chloride,
10 ml of ether, and 30 ml of ethyl acetate, a mixture
of 0.05 mol of ethyl 2-alkyl-2,4-dibromo-4-methyl-3-
oxopentanoate and 0.05 mol of corresponding al-
dehyde in 10 ml of a mixture of solvents was added
dropwise with stirring. The reaction mixture was
refluxed for 15 min, cooled, and then 0.1 mol of cor-
responding acyl chloride in 10 ml of a mixture of
solvents and 0.1 mol of tributylamine was added
dropwise with cooling. To bring the reaction to com-
pletion, the reaction mixture was heated for 15 min
and then cooled and hydrolyzed with 10% HCl. The
reaction products were extracted with ether. The ex-
tracts were dried with sodium sulfate, and the solvents
were removed in vacuo. Compounds IIIb IIIj were
crystallized from petroleum ether (70 100 C) CCl4
(1:1), and compound IIIa was twice distilled in vacuo.
Formula
C
H
C
H
VIIa
VIIb
VIIca
VIId
62.79
65.58
52.35
57.80
5.21 C21H21BrO3
5.65 C21H21NO5
4.12 C21H20Br2O3
62.84
68.66
52.50
5.24
5.72
4.17
4.59
4.53 C21H20BrClO3 57.86
a
Compound VIIc contains minor amounts of the O-acylation
1
product (ca. 10%). H NMR spectrum (DMSO-d ), , ppm:
0.90 s, 1.00 s (6H, Me ), 1.95 s (3H, Me), 5.02 d, 5.25 d (2H,
6
2
CH ), 5.23 s (1H, CH), 7.33 d, 7.49 d (4H, 4-BrC H ), 7.39 d,
2
6 4
b
7.55 d (4H, 4-BrC H ). Yields of compound prepared by
method a.
6
4
compounds suggest formation of two geometric
isomers in a 1:9 ratio. No signals assignable to the
O-alkylation products were found in the spectra of
both isomers.
Bis(3,5,5-trimethyl-6-phenyl-2-oxo-5,6-dihydro-
pyran-4-yl) succinate (V) was prepared similarly to
compounds IIIa IIIj using 0.05 mol of succinyl
chloride. Yield 30%, mp 198 199 C (from ethanol).
1H NMR spectrum (DMSO-d6), , ppm: 0.90 s, 1.00 s
(6H, Me2), 1.65 s (3H, Me), 3.03 s (2H, CH2), 5.40 s
EXPERIMENTAL
1
The H NMR spectra were recorded for DMSO-d6
solutions on Bruker DRX-500 (IIIe, IIIf, VIIc, VIId)
and Bruker AM-300 (IIIb IIId, IIIg IIIj, V) instru-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 5 2003

764
SHCHEPIN et al.
(1H, CH), 7.40 s (5H, C6H5). Found, %: C 70.19; H
6.15. C32H34O8. Calculated, %: C 70.33; H 6.23.
62.70; H 5.16. C21H21BrO3. Calculated, %: C 62.84;
H 5.24.
3-Alkyl-6-aryl-3-(4-R-benzyl)-5,5-dimethyl-
2,3,5,6-tetrahydropyrane-2,4-diones VIIa VIId.
a. To sodium methylate prepared from 0.03 mol of
sodium and 10 ml of MeOH, 0.02 mol of 3-alkyl-6-
aryl-5,5-dimethyl-2,3,5,6-tetrahydropyran-2-one or
0.02 mol of 3-alkyl-6-aryl-4-cyloxy-5,5-dimethyl-5,6-
dihydropyrane-2-one was added, followed by
0.02 mol of substituted p-bromobenzaldehyde, and
the mixture was stirred at 30 40 C for 30 min. After
the reaction had been complete, the alcohol was dis-
tilled off, the mixture was hydrolyzed, extracted with
ether, the solvents were removed, and the residue was
recrystallized from metanol.
,
-Bis(3,5,5-trimethyl-6-phenyl-2,4-dioxo-
2,3,5,6-tetrahydropyran-3-yl)-p-xylene. a. The syn-
thesis was performed by procedure a for compounds
VIIa VIId, using 0.04 mol of 3,5,5-trimethyl-6-
phenyl-2,3,5,6-tetrahydropyrane-2,4-dione and
0.02 mol of , -dibromo-p-xylene. Yield 10%, mp
275 276 C (from acetonitrile). 1H NMR spectrum
(CDCl3), , ppm: 0.72 s, 0.93 s (6H, Me2), 1.47 s (3H,
Me), 2.93 d, 3.30 d (2H, CH2), 3.87 s (1H, CH),
7.00 s (5H, C6H5), 6.87 7.10 m (4H, C6H4). Found,
%: C 76.24; H 6.62. C36H38O6. Calculated, %: C
76.33; H 6.71.
b. The synthesis was performed by procedure b
described for compounds VIIa VIId. Yield 6%, mp
195 196 C (from acetone). 1H NMR spectrum
(CDCl3), , ppm: 0.70 s, 0.88 s (6H, Me2), 1.50 s (3H,
Me), 2.92 d, 3.33 d (2H, CH2), 3.57 s (1H, CH),
7.00 s (5H, C6H5), 6.73 7.33 m (4H, C6H4). Found,
%: C 76.19; H 6.65. C36H38O6. Calculated, %: C
76.33; H 6.71. Isomer with mp 275 276 C (from
b. To sodium methylate prepared from 0.03 mol of
sodium and 10 ml of methanol and dissolved in 15 ml
of DMSO, 0.02 mol of 3-alkyl-6-aryl-5,5-dimethyl-
2,3,5,6-tetrahydropyran-2-one was added. The alcohol
formed was distilled off a water-jet-pump vacuum.
Then 0.02 mol of substituted benzyl bromide was
added, the mixture was stirred at 30 40 C for 30 min
and then poured into water. The precipitate formed
was filtered off and recrystallized from methanol,
acetonitrile, or acetone.
1
acetone). Yield 54%. H NMR spectrum corresponds
to that given for the product prepared by method a.
4-(4-Bromobenzoyloxy)-3,5,5-trimethyl-5,6-di-
hydropyran-2-one (VIIIa) was synthesized similarly
to compounds VIIa VIIId by method b, using
0.02 mol each of 3,5,5-trimethyl-6-phenyl-2,3,5,6-
tetrahydropyrane-2,4-dione and 4-bromobenzyl bro-
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no. 6, p. 808.
1
mide. Yield 11%, mp 174 175 C (from acetone). H
2. Lapkin, I.I. and Fotin, V.V., Zh. Org. Khim., 1975,
NMR spectrum (CDCl3 + CCl4), , ppm: 0.90 s,
1.03 s (6H, Me2), 2.00 s (3H, Me), 4.87 d, 5.23 d
(2H, CH2, J 12 Hz), 5.03 s (1H, CH), 7.23 d, 7.53 d
(4H, 4-BrC6H4), 7.30 s (5H, C6H5). Found, %: C
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