5-arylidene derivatives of meldrum's acid as synthons in pyrano[4,3-b]pyran synthesis

Article abstract of DOI:10.1007/s00706-007-0622-5

The reactions of 5-arylidene derivatives of Meldrum's acid with ethyl vinyl ether or N-vinyl-2-oxazolidinone yielded trans-trans-(2,4:4,7)-pyrano[4,3-b] pyrans, cis-trans-(2,4:4,7)-pyrano[4,3-b]pyrans, or diastereoisomeric mixtures of pyrano[4,3-b]pyrans

Full text of DOI:10.1007/s00706-007-0622-5

Monatshefte f u¨ r Chemie 138, 481–488 (2007)
DOI 10.1007/s00706-007-0622-5
Printed in The Netherlands
5-Arylidene Derivatives of Meldrum’s Acid as Synthons
in Pyrano[4,3-b]pyran Synthesis
Aleksandra Palasz1 , Katarzyna Jelska , Monika O z˙ o´ g , and Pawel Serda
;ꢀ
1
1
2
1
Department of Organic Chemistry, Jagiellonian University, Krak o´ w, Poland
Regional Laboratory, Jagiellonian University, Krak o´ w, Poland
2
Received September 28, 2006; accepted (revised) October 27, 2006; published online April 20, 2007
Springer-Verlag 2007
#
Summary. The reactions of 5-arylidene derivatives of
Meldrum’s acid with ethyl vinyl ether or N-vinyl-2-oxazo-
lidinone yielded trans-trans-(2,4:4,7)-pyrano[4,3-b]pyrans,
cis-trans-(2,4:4,7)-pyrano[4,3-b]pyrans, or diastereoisomeric
mixtures of pyrano[4,3-b]pyrans and reactions with 3,4-di-
hydro-2H-pyran afforded Michael adducts. The reactions of
jugate addition-cyclization with CH-acids like malo-
nonitrile or cyanoacetate [15–20]. It has been found
that cyano, alkoxycarbonyl, acyl, aryl, or phenylthio
substituents in the enone system enabled sequential
O-cyclization to the pyran ring. Therefore, the 5-
arylidene derivatives of Meldrum’s acid seem to be
excellent reagents in pyran synthesis both by HDA
reaction and by conjugate addition-cyclization. There
are very few examples in literature describing the
HDA reactions of 5-ylidene substituted Meldrum’s
acids with alkenes. Polansky et al. have described
cycloadditions of two alkylidene (R ¼ isopropyl,
t-butyl) and one 5-arylidene (Ar¼Ph) derivatives of
Meldrum’s acid to ethyl vinyl ether or 1,1-dimeth-
oxyethene [21]. They afford a mixture of cis=trans
diastereoisomers of pyrano[2,3-d][1,3]dioxin-4(5H)-
ones, but pure diastereoisomers have not been sepa-
rated from byproducts. Tietze et al. have used 5-ylidene
derivatives of Meldrum’s acid, possessing alkene sub-
stituents, in an intramolecular HDA reaction [22, 23].
5-arylidene derivatives of Meldrum’s acid with cyanoacetic
acid derivatives do not provide appropriate pyrans.
Keywords. Pyrans; ꢀ,ꢁ-Unsaturated ketone; Enol ethers;
Michael addition.
Introduction
Polyfunctionalized pyran derivatives are common
structural subunits in a variety of important natural
products, includingcarbohydrates, alkaloids, polyether
antibiotics, pheromones, and iridoids. The inverse-
electron-demand hetero-Diels-Alder (HDA) reactions
of ꢀ,ꢁ-unsaturated carbonyl compounds with elec-
tron-rich alkenes give excellent access to substituted
3
,4-dihydro-2H-pyrans [1–5]. The reactivity of ꢀ,ꢁ-
unsaturated carbonyl compounds can be enhanced by
introducing electron-withdrawing substituents [6–10].
Recently, we have reported that HDA reactions of
Results and Discussion
3
1
-cyano-1-oxa-1,3-butadienes with enol ethers [11,
2], styrenes [13], or N-vinyl-2-oxazolidinone [14] lead
The first aim of this work was to investigate reac-
tions of 5-arylidene Meldrum’s acids with different
alkenes possessing electron-donating groups: enol
ethers, N-vinyl-2-oxazolidinone, and p-substituted
styrene derivatives. We wanted to compare the reac-
tivity of the above-mentioned compounds towards
these former derivatives. The second aim was to
efficiently to 3,4-dihydro-2H-pyran-5-carbonitriles.
The same ꢀ,ꢁ-unsaturated carbonyl compounds
can be used as substrates in pyran synthesis by con-
ꢀ Corresponding author. E-mail: palasz@chemia.uj.edu.pl

4
82
A. Palasz et al.
study the Michael addition of the quoted ꢀ,ꢁ-unsa-
turated carbonyl compounds with cyanoacetic acid
derivatives as a potential method of pyran synthesis.
temperature for 1–2 days in methylene chloride (2a
and 2b) and in boiling acetonitrile, or else toluene
(2c and 2d). They afforded one diastereoisomer of
pyrano[4,3-b]pyrans 4a, 4b, 3e, and 3f or diaste-
reoisomeric mixture 3c and 3d in 33–46% yield
(Scheme 1). The progress of the reactions was moni-
tored by TLC. Compounds 4a, 4b, and 3c–3f were
separated by column chromatography and purified
further by crystallization. Since the reactions of sty-
renes 2c–2d with 1a and 1b in methylene chloride
at room temperature failed, the reaction mixtures
were heated in boiling acetonitrile or toluene. In all
cases unchanged compounds 1a and 1b were iso-
lated. According to Ref. [21], we expected to obtain
5
-Arylidene derivatives of Meldrum’s acid 1a–1d
were obtained according to the methods described in
literature [24]. It is worth to note that Knoevenagel
condensations of Meldrum’s acid and aldehydes are
not quite selective and often an undesirable bisad-
duct is obtained due to Michael addition with a
second molecule of Meldrum’s acid. New methods
of conducting these Knoevenagel condensations are
still investigated [25–28].
The reactions of potential heterodienes 1a–1d
with dienophiles 2a–2d were performed at ambient
Scheme 1

5
-Arylidene Derivatives of Meldrum’s Acid
483
Scheme 2
1
13
pyrano[2,3-d][1,3]dioxin-4(5H)-one derivatives by
HDA cycloadditions, however, the described reactions
provide pyrano[4,3-b]pyrans. The proposed mecha-
nism of the formation of 3a–3f is shown in Scheme 2.
In the first step, a Michael addition of reactant
elemental analysis. H and C signal assignments
were confirmed by two-dimensional NMR COSY
and HETCOR spectra. The relative cis and trans
configuration of C-2, C-4, C-7 substituents were as-
1
signed on the basis of H NMR spectra and crystallo-
1
graphic methods. In the H NMR spectra of 4a and
2
a–2b to ꢀ,ꢁ-unsaturated ketone 1a–1d afforded in-
termediates C, followed by ring closure leading to
intermediates D. Next, a Michael addition of com-
pounds 2a–2b across the enone moiety of ꢀ,ꢁ-unsat-
urated lactone D furnished E. The elimination of
acetone afforded intermediate F possessing a car-
boxylate anion and an oxonium or immonium func-
tionality. In the final step, addition of the carboxylate
anion to the onium functionalities resulted in the
unexpected pyrano[4,3-b]pyrans 3a–3f. The com-
pounds 3a and 3b could not be recovered unchanged
and after chromatography 4a and 4b were obtained.
Probably, 3a and 3b hydrolyzed during column chro-
matography on silica gel and recrystallization to 2-
hydroxy pyrano[4,3-b]pyrans 4a and 4b (Scheme 2).
Compounds 4a, 4b, and 3c–3f were charac-
4b the signal of 7-H appeared as a doublet of dou-
blets at ꢂ ¼ 5.54–5.58 ppm with the coupling con-
Fig. 1. A perspective view of 4a with the atom numbering
scheme
1
13
terized by H, C NMR, IR, mass spectra, and

4
84
A. Palasz et al.
3
1
Table 1. Signals of proton 2-H, 4-H, and 7-H in H NMR
spectra of pyrano[4,3-b]pyrans 4a, 4b, 3e, and 3f
stants J ¼ 5.0–6.0 and 3.9–4.5 Hz, due to coupling
with two protons at C-8 (Table 1). Thus, 7-H occu-
pies an equatorial position, and the ethoxy group
adopts an axial orientation (Fig. 1). For compounds
Compound
m 2-H
ꢂ=ppm
m 4-H
ꢂ=ppm
dd 7-H
ꢂ=ppm
J3ax;2jJ3eq;2
J3ax;4jJ3eq;4jJ8;4
J8ax;7jJ8eq;7
4
a and 4b signals of protons at C-2 (ꢂ ¼ 5.08–
Hz
Hz
Hz
5
are broad and it is impossible to assign the complete
1
stereochemistry. A H NMR spectrum of 4b was also
recorded at temperature 373 K. It is worth to note
that in the spectrum measured at higher temperature
the signal one from the protons 8-H is a doublet
of doublets at ꢂ ¼ 2.58 ppm with the coupling con-
.18 ppm) and C-4 (ꢂ ¼ 3.75–3.97 ppm) positions
4
a
5.08 br t
6.5
5.18 br
3.75 br
5.54
5.0j4.5
4
b
3.97 br t
5.58
6.0j3.9
6.04
6
3.98 ddd
.6
3
e
5.72 dd
11.7j1.6
5.72 dd
11.0j1.5
11.4j6.6j3.0
12.6j3.6
3
f
4.20 ddd
11.5j6.0j2.75
6.03
12.5j3.8
2
3
5
stants J ¼ 17.4 Hz, J ¼ 6.3 Hz, and J ¼ 2.4 Hz. The
third coupling constant refers to the coupling of pro-
ton 8-H with the proton 4-H. In the COSY spectrum
of 4b there is a cross peak correlating 4-H with 8-H.
The final stereochemistry of 4a and 4b was de-
termined by X-ray analysis of the derivative 4a. A
perspective view of the molecule with the crystal-
lographic numbering scheme is given in Fig. 1. The
asymmetric unit contains two molecules of the com-
pound (for clarity, only one was presented in Fig. 1)
with slightly different conformations (the RMS devi-
Fig. 2. Cis-trans(2,4:4,7) configurations of pyrano[4,3-b]
1
pyrans 3e and 3f based on H NMR analysis
˚
ation of superimposed molecules is equal to 0.4 A).
The crystal structure is stabilized by several inter-
molecular hydrogen bonds, of which the strongest
1
In the H NMR spectra of 3e and 3f the signal of
4-H appears as a doublet of doublets at ꢂ ¼ 3.98–
ꢂ
3
˚
ꢂ
are O11–H11 ꢁ ꢁ ꢁ O7 (2.957 A, 120.6 ) and O11–
4.20 ppm with the coupling constants J ¼ 11.4–
5
˚
H11 ꢁ ꢁ ꢁ O12 (2.854 A, 171.2 ). The hydroxy group
at C-2 occupies an equatorial position, the aryl
group 4-Ar adopts a pseudo-axial orientation, and
11.5, 6.0–6.6 Hz and J ¼ 2.75–3.0 Hz, due to cou-
pling with two protons at C-3 (Table 1). The third
value refers to the coupling of 4-H with pseudo-axial
proton at position C-8 (8-H for 3e ꢂ ¼ 2.96 ppm, ddd,
J ¼ 17.1, 12.6, 3.1 Hz and for 3f ꢂ ¼ 3.20 ppm, ddd,
J ¼ 17.5, 12.8, 3.0 Hz). Thus, 4-H occupies a pseudo-
axial position, and the aryl groups Ar adopt pseudo-
equatorial orientation (Fig. 2). The signal of proton
7-H is a doublet of doublets at ꢂ ¼ 6.03–6.04 ppm
7
-ethoxy group is in the axial position (Fig. 1). The
relative configurations of substituents at stereogenic
positions are trans-trans (2,4:4,7).
Compounds 3c and 3d were obtained as a mixture
of diastereoisomers and we were not able to separate
the pure diastereoisomers by column and PTL chro-
matography. It proved likewise impossible to deter-
mine the ratio of particular diastereoisomers on the
3
with the coupling constants J ¼ 12.5–12.6 and
3.6–3.8 Hz (Table 1), hence 7-H must be axial and
the oxazolidinyl moiety is in the equatorial position
(Fig. 2). Thus we can assume that for compounds 3e
and 3f the relative configurations of substituents at
C-2, C-4, and C-7 positions are cis-trans (2,4:4,7).
Next, the reactions of 5-arylidene Meldrum’s
acids 1a and 1b with cyclic enol ether 5 were stud-
ied. The reactions of compounds 1a and 1b with
3,4-dihydro-2H-pyrane 5 were performed in methy-
lene chloride at room temperature for 1–2 days and
Michael adducts 6a and 6b were obtained with 49–
52% yields (Scheme 1). Michael adducts 6a and 6b
structure was established on the basis of analytical
1
basis of H NMR analysis. For compounds 3e and 3f
the configurations were deduced from the chemical
shift values and coupling constants of protons 2-H,
4
-H, and 7-H of the pyrano[4,3-b]pyran (Table 1).
1
The H NMR spectra of 3e and 3f reveal the
signals of proton 2-H as a doublet of doublets at
ꢂ ¼ 5.72 ppm with large and small coupling con-
3
stants ( J ¼ 11.0–11.7 and 1.5–1.6 Hz) due to cou-
pling with the axial and equatorial protons 3-H.
Thus, the hemiaminalic proton at C-2 obviously
adopts the axial position, and the large oxazolidinyl
moiety occupies the equatorial position (Fig. 2).

5
-Arylidene Derivatives of Meldrum’s Acid
485
1
13
and spectroscopic data. H and C signal assign-
ments were confirmed by two-dimensional NMR
COSY and HETCOR spectra. The presence of two
The second potential method of pyran synthesis, i.e.
reactions of 5-arylidene Meldrum’s acids with cyano-
acetic acid derivatives lead to arylidenemalononitriles
and cannot be used to obtain pyrans.
1
singlets at ꢂ ¼ 1.69 ppm and ꢂ ¼ 1.78 ppm in the H
NMR spectra indicates that in contrast to the reac-
tions described above the elimination of acetone
does not occur and the product contains 1,3-
Experimental
1
dioxin-4,6-dione ring. The H NMR spectra revealed
a doublet at ꢂ ¼ 4.01–4.06 ppm with coupling con-
Melting points were determined on a Boetius hot stage ap-
1
paratus. IR spectra: Bruker IFS 48 in KBr pellets. H NMR,
3
1
3
stants J ¼ 3.0–3.3 Hz for proton 5-H and a doublet
C NMR, COSY, and HETCOR spectra: Bruker AMX 500
3
1
( H: 500.14 MHz, C: 125.76 MHz), Bruker Avance II 300
13
at ꢂ ¼ 4.49–4.57 ppm ( J ¼ 3.0 Hz) for aliphatic
1
13
0
( H: 300.18 MHz, C: 75.48 MHz), in CDCl , DMSO-d with
3 6
CHAr proton coupled with 5-H. The proton at C-6
position resonates as a doublet at ꢂ ¼ 6.41 ppm with
TMS as an internal standard. Mass spectra: Finningan Mat 95
70 eV). Microanalyses were performed with Euro EA 3000
(
4
J ¼ 0.6 Hz.
Elemental Analyzer, their results agreed satisfactorily with
the calculated values. Crystallographic Data: KappaCCD
(Nonius) diffractometer using MoKꢀ radiation, X-ray data
measured at room temperature. The structure was solved by
direct methods and refined by the full-matrix least-squares
In the next series of experiments we investigated
the reactions of 5-arylidene derivatives of Meldrum’s
acids 1a–1c with cyanoacetic acid derivatives 7a and
7
b as a potential method of pyran synthesis. These
2
method on F using SHELX97 program system.
reactions were carried out in boiling acetonitrile, in
the presence of piperidine and resulted in formation
of the arylidenemalononitriles 8a–8c and arylidene
derivative methyl cyanoacetate 8d in yields of 59–
64% (Scheme 1). Compounds 8a–8d have been ex-
tensively described in literature [29, 30].
Meldrum’s acid was obtained according to a procedure
described in Ref. [31]. 5-Arylidene-2,2-dimethyl-4,6-dioxo-
1,3-dioxanes 1a–1d were prepared by a procedure reported
in Ref. [24]. N-Vinyl-2-oxazolidinone 2b was synthesized ac-
cording to the procedure described in Ref. [32].
General Procedure for the Preparation of 4a, 4b, 3c–3f, 6a,
and 6b
A solution of the 5-arylidene derivatives of Meldrum’s acid
In the first step of the reactions the Michael ad-
ducts A are furnished (Scheme 1). Intermediates A
did not undergo cyclization with 4H-pyran B forma-
tion but the elimination of Meldrum’s acid led to
undesired 8a–8d. We tried to carry out the reaction
of p-methoxybenzylidene Meldrum’s acid 1a with
malononitrile 7a under mild conditions. The reagents
mixture and piperdine in acetonitrile were kept at
room temperature for 2 weeks. The result was the
same as previously, but the time needed to complete
the conversion was longer.
3
1
1
a–1d (2mmol) in 20cm anhydrous dichloromethane and
.44g ethyl vinyl ether (2a, 20mmol, 10 equiv), 0.45g
N-vinyl-2-oxazolidinone (2b, 4 mmol, 2 equiv), 4 mmol styr-
enes 2c and 2d (2 equiv) or 1.68 g 3,4-dihydro-2H-pyran 5
(20 mmol, 10 equiv) was kept at room temp. for the time 1 day
(4b, 3e, 3f, 6b) and 2 days (4a, 3c, 3d, 6a). The progress of the
reactions was monitored by TLC. The solvent was evaporated
and the mixture was separated and purified by column chroma-
tography on silica gel using petrol ether:t-butyl methyl ether
1:2 (4a), t-butyl methyl ether (3c, 3d, 4b), CHCl : methanol
3
In conclusion, reactions of 5-arylidene derivatives
of Meldrum’s acid with ethyl vinyl ether and N-
vinyl-2-oxazolidinone lead to pyrano[4,3-b]pyrans,
as the result of reactions: a Michael addition, a cycli-
zation, a Michael addition, an elimination of acetone,
and finally ring closure by addition. The configura-
tions of isolated diastereoisomers of pyrano[4,3-b]-
pyrans were assigned as trans-trans (2,4:4,7) and
cis-trans (2,4:4,7). The present results indicate that
20:1 (3e, 3f), or CHCl (6a, 6b) as an eluent. Recrystallization
3
from t-butyl methyl ether (4a, 4b, 6a), methanol (3e), CHCl3
(3f), t-butyl methyl ether:methanol 3:1 (6b) gave crystalline
colorless products. Compounds 3a and 3b hydrolyzed during
column chromatography and recrystallization yielded 4a and
4
b. Since styrenes 2c and 2d did not react with 5-arylidene
derivatives of Meldrum’s acid 1a and 1b under the reaction
conditions described above, we changed the solvent to anhy-
drous acetonitrile or toluene and appropriate solutions were
refluxed for 24 h. After this time substrate 1a and 1b was
separated from the reaction mixture.
5
-arylidene derivatives of Meldrum’s acid can act as
valuable reagents in pyran synthesis. The reactions of
-arylidene-2,2-dimethyl-4,6-dioxo-1,3-dioxaneswith
(
2RS,4RS,7RS)-7-Ethoxy-2-hydroxy-4-(4-methoxyphenyl)-
-oxo-2,3,4,5,7,8-hexahydropyrano[4,3-b]pyran
4a, C H O )
5
5
cyclic enol ether result in Michael adducts. Styrenes
are not suitable reagents on account of their inertness
towards 5-arylidene derivatives of Meldrum’s acid.
(
1
7
20
6
ꢂ
Colorless crystals; mp 175 C; yield 33%; IR (KBr): ꢃꢀ ¼ 3305
(OH), 2979, 2932, 2834 (CH), 1670 (C¼O), 1635 (C¼C), 1272,

4
86
250, 1159, 1132, 1011 (C–O) cm ; H NMR (500.14MHz,
A. Palasz et al.
ꢃ1
1
1
2,7-Diethoxy-4-(2-furyl)-5-oxo-2,3,4,5,7,8-hexahydropyrano
DMSO-d ): ꢂ ¼ 1.16 (t, J ¼ 7.0 Hz, 3 OCH CH ), 1.89 (br d,
6
2
3
[4,3-b]pyran (3c, C H O )
1
6 20 6
J ¼ 13.5Hz, 1 3-H ), 1.98 (ddd, J ¼ 5.5, 13.5, 6.0 Hz, 1 3-
ax
Pale yellow oil; yield 40%; IR (film): ꢃꢀ ¼ 3110, 3075, 2964,
H ), 2.57 (dd, J ¼ 17.0, 5.0 Hz, 1 8-H), 2.93 (dd, J ¼ 17.0,
eq
2928 (CH), 1712 (C¼O), 1641 (C¼C), 1169, 1132, 1047
ꢃ1
1
4
.0 Hz, 1 8-H), 3.63 (dq, J ¼ 14.5, 7.0 Hz, 1 OCH CH ), 3.72
2
3
(C–O) cm ; H NMR (300.18 MHz, CDCl ): ꢂ ¼ 1.19 (m,
3
(
s, 3 OCH ), 3.75 (br, 1 4-H), 3.81 (dq, J ¼ 14.5, 7.0Hz, 1
2 3
3
6 OCH CH ), 2.12 (m, 2 3-H), 2.61 (m, 2 8-H), 3.78 (m,
2
3
OCH CH ), 5.08 (t, J ¼ 6.5 Hz, 1 2-H), 5.54 (dd, J ¼ 5.0,
4 OCH CH ), 4.15 (m, 1 4-H), 5.27 (m, 1 2-H), 5.49 (m, 1
2 3
4
.5 Hz, 1 7-H), 6.84 (d, J ¼ 8.5 Hz, 2 ArH), 7.09 (d, J ¼ 8.5 Hz,
7
-H), 6.69 (m, 1 H-furyl), 7.62 (m, 1 H-furyl), 7.85 (m, 1 H-
1
ArH), 7.53 (br, 1 OH) ppm; C NMR (125.76 MHz;
3
13
2
furyl) ppm; C NMR (75.48 MHz, CDCl ): ꢂ ¼ 14.1, 15.9
3
DMSO-d ): ꢂ ¼ 14.8 (OCH CH ), 32.7 (C-8), 33.7 (C-4),
6
2
3
(OCH CH ), 30.5, 31.7, 33.8, 34.2, 36.7, 37.5, 37.9 (C-8,
2
3
3
7.2 (C-3), 54.9 (OCH ), 64.0 (OCH CH ), 93.1 (C-2), 97.9
3 2 3
C-4, C-3), 63.8, 64.7, 64.9, 65.3, 65.4, 65.5, 65.6 (OCH CH ),
2 3
(
(
(
C-7), 100.5 (C-4a), 113.6, 128.2, 136.2, 157.6 (ArC), 163.3
C-8a), 163.9 (C-5) ppm; MS (EI, 70 eV): m=z (%) ¼ 320
9
1
1
1
6.8, 97.2, 98.3, 98.4, 99.2, 99.7, 99.8 (C-2, C-7, C-4a), 115.9,
16.6, 116.8, 124.2, 124.5, 124.7, 126.3, 126.7, 127.8, 146.9,
þ
71)[M]
ꢁ
, 302 (17), 276 (16), 275 (32), 274 (18), 231 (27),
0
0
0
0
48.5, 149.6, 150.2 (C-2 , C-3 , C-4 , C-5 furyl), 161.7, 161.9,
62.5, 162.7 (C-8a, C-5) ppm; MS (EI, 70eV): m=z (%) ¼ 308
2
30 (29), 205 (33), 134 (100), 99 (94), 71 (81).
Crystal structure analysis: Compound 4a with formula
C H O crystallizes in the monoclinic system, space
þꢅ
(100) [M] , 263 (21), 236 (19), 218 (25), 189 (49), 163 (43),
99.1 (27), 94 (21), 71 (19).
1
7
20
6
group P2 =a, with unit cell parameters a ¼ 16.8953(2),
1
˚
ꢂ
b ¼ 9.5789(2), c ¼ 21.5910(3) A, ꢁ ¼ 112.070(1) , V ¼
3
0
˚
3
238.2(1) A , Z ¼ 4, Z 8. A total of 7412 independent reflec-
2,7-Diethoxy-4-(2-thienyl)-5-oxo-2,3,4,5,7,8-hexahydropyrano
tions (R(int) ¼ 0.0474) were collected on a sample (size
[4,3-b]pyran (3d, C H O S)
16 20 5
3
0
.25ꢄ0.20ꢄ0.20mm ). Final R indices for I>2ꢄ(I) were
equal R1 ¼ 0.0487, wR2 ¼ 0.1143 and R1 ¼ 0.0850, wR2 ¼
.1313 for all data. The final difference Fourier map of elec-
tron density was featureless with the largest peak and hole of
ꢀ
Pale yellow oil; yield 38%; IR (film): ꢃ ¼ 3103, 3068, 2977,
2
931 (CH), 1717 (C¼O), 1652 (C¼C), 1174, 1126, 1051
ꢃ1 13
0
(C–O) cm
;
C NMR (300.18 MHz, CDCl ) ꢂ ¼ 1.23 (m,
3
6
OCH CH ), 4.23 (m, 1 4-H), 5.14 (m, 1 2-H), 5.43 (m, 1 7-H),
6
OCH CH ), 2.24 (m, 2 3-H), 2.69 (m, 2 8-H), 3.71 (m, 4
2 3
˚
ꢃ3
0
.154 and ꢃ0.196 e ꢁ A . The structural data were deposited
2
3
1
.88 (m, 2H-thienyl), 7.15 (m, 1H-thienyl) ppm; C NMR
3
at the Cambridge Crystallographic Data Centre. These data
can be obtained free of charge via www.ccdc.cam.ac.uk=
conts=retrieving.html (or from the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: þ44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk) under reference number CCDC
(
75.48MHz, CDCl ): ꢂ ¼ 14.9, 15.1 (OCH CH ), 30.2, 30.3,
3
2
3
3
6
9
1
1
1
0.4, 33.2, 35.9, 36.1, 36.5, 37.4 (C-8, C-4, C-3), 64.4, 64.6,
4.9, 65.0, 65.1, 65.2, 65.5, 65.6 (OCH CH ), 97.0, 97.3, 98.2,
2
3
8.3, 99.2, 99.4, 99.9 (C-2, C-7, C-4a), 122.9, 123.6, 123.9,
24.2, 124.5, 124.7, 126.3, 126.4, 126.8, 127.0, 146.9, 147.4,
6
17449.
0
0
0
0
47.6, 147.7 (C-2 , C-3 , C-4 , C-5 thienyl), 161.0, 161.3,
62.0, 162.3 (C-8a, C-5) ppm; MS (EI, 70eV): m=z (%) ¼
(2RS,4RS,7RS)-7-Ethoxy-2-hydroxy-4-(4-nitrophenyl)-5-oxo-
þꢅ
2
,3,4,5,7,8-hexahydropyrano[4,3-b]pyran (4b, C H NO )
17
324 (100%) [M] , 279 (29), 252 (21), 234 (31), 205 (60), 179
(40), 167 (33), 137 (23), 110 (23), 99.1 (33), 71 (17).
1
6
7
ꢂ
Colorless crystals; mp 195 C; yield 41%; IR (KBr): ꢃꢀ ¼ 3334
(
(
(
OH), 3108, 3072, 3045, 2989, 2966 (CH), 1659 (C¼O), 1635
ꢃ1
1
C¼C), 1515, 1349 (NO ), 1145, 1085 (C–O) cm ; H NMR
2
(
2RS,4SR,7SR)-4-(4-Methoxyphenyl)-5-oxo-2,7-di(2-oxo-3-
oxazolidinyl)-2,3,4,5,7,8-hexahydropyrano[4,3-b]pyran
(3e, C21
500.14 MHz, DMSO-d , 293 K): ꢂ ¼ 1.16 (t, J ¼ 7.1 Hz,
6
3
OCH CH ), 1.91 (br d, J ¼ 13.8Hz, 1 3-H ), 2.11 (ddd,
eq
2
3
ax
J ¼ 6.6, 6.6, 13.8Hz, 1 3-H ), 2.58 (dd, J ¼ 17.4, 6.0Hz, 1 8-
H N O )
22 2 8
ꢂ
H), 2.97 (dd, J ¼ 17.4, 3.9 Hz, 1 8-H), 3.64 (dq, J ¼ 9.6, 7.1 Hz,
Colorless crystals; mp 242 C; yield 42%; IR (KBr): ꢃꢀ ¼ 3134,
2996, 2959, 2919 (CH), 1766, 1749, 1702 (C¼O), 1647
1
OCH CH ), 3.82 (dq, J ¼ 9.6, 7.1Hz, 1 OCH CH ), 3.97 (br
2
3
2
3
ꢃ1
1
; H NMR
t, J ¼ 6.6 Hz, 1 4-H), 5.18 (br, 1 2-H), 5.58 (dd, J ¼ 6.0, 3.9 Hz,
7-H), 7.51 (d, J ¼ 8.5 Hz, 2 ArH), 7.69 (br, 1 OH), 8.14 (d,
(C¼C), 1274, 1192, 1068, 1034 (C–O) cm
1
(500.14 MHz, CDCl ): ꢂ ¼ 2.03 (ddd, J ¼ 11.5, 11.5, 13.8Hz,
3
1
J ¼ 8.5 Hz, 2 ArH) ppm; H NMR (500.14 MHz, DMSO-d ;
1 3-H ), 2.37 (ddd, J ¼ 1.8, 6.6, 13.5Hz, 1 3-H ), 2.53 (dd,
6
ax
eq
3
2
2
73 K) 1.17 (t, J ¼ 7.2 Hz, 3 OCH CH ), 1.97 (m, 1 3-H ),
J ¼ 3.7, 17.5Hz, 1 8-H ), 2.96 (ddd, J ¼ 17.1, 12.6, 3.1Hz,
2
3
ax
eq
0
.19 (m, 1 3-H ), 2.58 (ddd, J ¼ 17.4, 6.3, 2.4Hz, 1 8-H),
eq
1 8-H ), 3.60 (m, 2 4 -H), 3.78 (s, 3OCH ), 3.74 (dd, J ¼ 17.1,
ax
3
0
0
00
.90 (dd, J ¼ 17.4, 3.9 Hz, 1 8-H), 3.66 (dq, J ¼ 9.9, 6.9Hz, 1
8.0 Hz, 1 4 -H), 3.85 (dd, J ¼ 17.1, 8.2 Hz, 1 4 -H), 3.98 (ddd,
0 00
ax
OCH CH ), 3.82 (dq, J ¼ 9.9, 6.9 Hz, 1 OCH CH ), 3.98 (t,
J ¼ 11.4, 6.6, 3.0Hz, 1 4-H ), 4.42 (m, 4 5 -H, 5 -H), 5.72
2
3
2
3
J ¼ 6.0 Hz, 1 4-H), 5.20 (br, 1 2-H), 5.54 (dd, J ¼ 6.3, 4.2 Hz,
(dd, J ¼ 11.7, 1.6 Hz, 1 2-H ), 6.04 (dd, J ¼ 12.6, 3.6Hz, 1
ax
1
7-H), 7.25 (br, 1 OH), 7.47 (d, J ¼ 8.7 Hz, 2 ArH), 8.09 (d,
7-H), 6.85 (d, J ¼ 8.7 Hz, 2ArH), 7.12 (d, J ¼ 8.7Hz, 2ArH)
1
3
13
J ¼ 9.0 Hz, 2 ArH) ppm; C NMR (125.76 MHz, DMSO-d ):
ppm; C NMR (125.76 MHz, CDCl ): ꢂ ¼ 31.3 (C-8), 37.2
6
3
0 00 0
(C-4), 37.5 (C-3), 39.8 (C-4 , C-4 ), 55.31 (OCH ), 62.6 (C-5 ,
3
ꢂ ¼ 14.9 (OCH CH ), 32.9 (C-8), 34.3 (C-4), 36.6 (C-3), 64.2
2
3
00
(OCH CH ), 92.8 (C-2), 98.1 (C-7), 99.9 (C-4a), 123.4, 128.4,
3
C-5 ), 78.7 (C-2), 82.0 (C-7), 105.9 (C-4a), 114.4, 127.7,
00
2
0
1
28.7, 129.1, 146.0, 152.6 (ArC), 163.9 (C-8a), 164.1 (C-5)
þ
133.8, 157.1 (ArC), 157.4, 158.6 (C-2 , C-2 ), 163.5 (C-8a),
163.7 (C-5) ppm; MS (EI, 70eV): m=z (%) ¼ 430 (29%)
ppm; MS (EI, 70eV): m=z (%) ¼ 335 (20) [M]
ꢁ
, 317 (12),
þꢅ
290 (23), 289 (17), 244 (15), 220 (15), 218 (19), 158 (67), 99
[M] , 343 (29), 317 (45), 273 (17), 256 (16), 204 (36),
113 (100).
(100), 72 (64), 71 (88).

5
-Arylidene Derivatives of Meldrum’s Acid
487
(
2RS,4SR,7SR)-4-(4-Nitrophenyl)-5-oxo-2,7-di(2-oxo-3-
oxazolidinyl)-2,3,4,5,7,8-hexahydropyrano[4,3-b]pyran
3f, C H N O )
hydrous acetonitrile a few drops of piperidine were added.
The reaction mixtures were refluxed for 3 h. The progress of
the reactions was monitored by TLC. The solvent was evap-
orated and the oily residue was treated with methanol. The
precipitate was filtered off and recrystallized from metha-
nol. Reactions led to arylidenemalononitriles 8a–8c or
arylidene derivative of methyl cyanoacetate 8d in yields of
(
2
0
19
3
9
ꢂ
Colorless crystals; mp 233 C; yield 46%; IR (KBr): ꢃꢀ ¼
3
1
(
(
6
3
4
4
118, 3073, 2964, 2921 (CH), 1765, 1755, 1691 (C¼O),
646 (C¼C), 1515, 1347 (NO ), 1275, 1194, 1109, 1070
2
ꢃ1
1
C–O) cm ; H NMR (300.18 MHz, DMSO-d ): ꢂ ¼ 2.02
6
5
3
9–64%. Compounds 8a–8d are described in Refs. [29,
0]. Reaction of 1.31 g p-methoxybenzylidene Meldrum
ddd, J ¼ 11.0, 11.75, 12 Hz, 1 3-H ), 2.37 (ddd, J ¼ 1.5,
ax
.3, 13.3 Hz, 1 3-H ), 2.67 (dd, J ¼ 3.5, 17.5 Hz, 1 8-H ),
0
ax
eq
eq
acid 1a (5 mmol) and 0.40 g malononitrile (7a, 6 mmol) in
3
20 cm acetonitrile solution with a few drops of piperidine
was carried out at room temperature for 2 weeks. After
further purification arylidenemalononitrile 8a was isolated
in 61% yield.
.20 (ddd, J ¼ 17.5, 12.8, 3.0 Hz, 1 8-H ), 3.68 (m, 4 4 -H,
0
0
-H), 4.20 (ddd, J ¼ 11.5, 6.0, 2.75 Hz, 1 4-H ), 4.38 (m,
ax
0
00
5 -H, 5 -H), 5.72 (dd, J ¼ 11.0, 1.5 Hz, 1 2-H ), 6.03
ax
(
8
dd, J ¼ 12.5, 3.8 Hz, 1 7-H), 7.58 (d, J ¼ 9.0 Hz, 2ArH),
1
3
.17 (d, J ¼ 9.0 Hz, 2ArH) ppm; C NMR (75.48 MHz,
DMSO-d ): ꢂ ¼ 30.3 (C-8), 35.2 (C-4), 37.3 (C-3), 39.5
6
0 00 0 00
C-4 , C-4 ), 62.6 (C-5 , C-5 ), 78.8 (C-2), 81.7 (C-7),
(
1
1
02.9 (C-4a), 123.5, 128.2, 146.1, 151.8 (ArC), 156.8,
0
References
00
56.9 (C-2 , C-2 ), 163.6 (C-8a), 163.9 (C-5) ppm; MS
þꢅ
[1] Boger DL, Weinreb SN (1987) Hetero Diels-Alder
Methodology in Organic Synthesis, Academic Press,
San Diego
(
(
(
EI, 70 eV): m=z (%) ¼ 445 (35) [M] , 399 (14), 358
25), 332 (58), 312 (11), 289 (13), 287 (21), 271 (17), 219
32), 113 (100).
[
[
2] Tietze LF, Kettschau G (1997) Top Curr Chem 189: 1
3] Tietze LF, Harfiel U, Hubsch T, Voss E, Wichmann J
5
2
-[(3,4-Dihydro-2H-pyran-5-yl)(4-methoxyphenyl)methyl]-
(1991) Chem Ber 124: 881
,2-dimethyl-1,3-dioxane-4,6-dione (6a, C H O )
1
9 22 6
[4] Ager DJ, East MB (1993) Tetrahedron 49: 5683
[5] Tietze LF (1990) J Heterocycl Chem 27: 45
[6] John RA, Schmidt V, Wyler H (1987) Helv Chim Acta
ꢂ
Colorless crystals; mp 109 C; yield 49%; IR (KBr): ꢃꢀ ¼ 3058,
3
1
030, 2956, 2941, 2919, 2865, 2823 (CH), 1789, 1754 (C¼O),
ꢃ1
1
672 (C¼C), 1275, 1015 (C–O) cm ; H NMR (300.18 MHz,
7
0: 600
0
CDCl ) ꢂ ¼ 1.69 (s, 3CH ), 1.79 (s, 3CH ), 1.87 (m, 4 3 -H,
3
3
3
[
[
7] Yamauchi M, Katajama S, Baba O, Watanabe T (1983)
J Chem Soc Chem Commun: 281
8] Dvorak D, Arnold Z (1982) Tetrahedron Lett 23: 4401
0
0
4
1
-H), 3.83 (s, 3OCH ), 3.92 (m, 2 2 -H), 4.01 (d, J ¼ 3.0 Hz,
3
0
5-H), 4.49 (d, J ¼ 3.0 Hz, 1ArCH), 6.39 (d, J ¼ 0.7 Hz, 1 6 -
H), 6.79 (d, J ¼ 8.5 Hz, 2ArH), 7.12 (d, J ¼ 8.5 Hz, 2ArH)
1
3
0
[9] Haag-Zeino B, Schmidt RR (1990) Liebigs Ann Chem:
197
10] Dujardin G, Rossignol, S, Brown E (1996) Tetrahedron
2: 4007
11] Bogdanowicz-Szwed K, Palasz A (1995) Monatsh Chem
26: 1341
12] Bogdanowicz-Szwed K, Palasz A (1997) Monatsh Chem
28: 1157
13] Bogdanowicz-Szwed K, Palasz A (2001) Z Naturforsch
6b: 416
14] Palasz A (2005) Org Biomol Chem 3: 3207
15] Quinteiro M, Seoane C, Soto JL (1977) Tetrahedron Lett
3: 1835
[16] Soto JL, Seoane C, Martin N, Blanco LA (1983) Het-
erocycles 20: 803
17] Soto JL, Seoane C, Martin N, Quinteiro M (1984)
Heterocycles 22: 1
[18] Ciller JA, Martin N, Seoane C, Soto JL (1985) J Chem
Soc Perkin Trans 1: 2581
19] Martin N, Martinez-Grau A, Seoane C, Marco JL, Albert
A, Cano FH (1993) Liebigs Ann Chem: 801
20] Bogdanowicz-Szwed K, Budzowski A (1999) Monatsh
Chem 130: 545
21] Bitter J, Leitich J, Partale H, Polansky OE, Reimer W,
Ritter-Thomas U, Schlamann B, Stilkerieg B (1980)
Chem Ber 113: 1020
ppm; C NMR (75.48 MHz, CDCl ): ꢂ ¼ 21.8, 22.9 (C-3 ,
3
1
0
C-4 ), 27.4 (CH ), 29.0 (CH ), 48.6 (Ar-CH), 49.9 (C-5),
3
3
[
[
[
[
0
0
5
5.3 (OCH ), 66.2 (C-2 ), 106.0 (C-2), 110.9 (C-5 ), 113.59,
3
5
0
1
(
2
28.35, 136.8, (ArC), 144.1 (C-6 ), 157.3 (ArC), 164.2, 165.1
,
88 (6), 262 (6), 260 (47), 203 (100.00), 143 (7), 84 (8).
C-4, C-6) ppm; MS (EI, 70eV): m=z (%) ¼ 346 (9) [M]þꢅ
1
1
5
-[(3,4-Dihydro-2H-pyran-5-yl)(4-nitrophenyl)methyl]-2,2-
dimethyl-1,3-dioxane-4,6-dione (6b, C H NO )
1
8
19
7
5
ꢂ
Colorless crystals; mp 136 C; yield 52%; IR (KBr): ꢃꢀ ¼ 3114,
[
[
3
1
1
100, 3048, 3000, 2986, 2963, 2941, 2923, 2878 (CH), 1787,
746 (C¼O), 1669 (C¼C), 1512, 1342 (NO ), 1209, 1148,
0 0 0
s, 3CH ), 1.78 (s, 3CH ), 1.91 (m, 4 3 -H, 4 -H), 3.96 (m, 2 2 -
3 3
2
ꢃ1
1
017 (C–O) cm ; H NMR (300.18 MHz, CDCl ): ꢂ ¼ 1.69
3
(
H), 4.06 (d, J ¼ 3.3 Hz, 1 5-H), 4.57 (d, J ¼ 3.0 Hz, 1ArCH),
[
0
6
.41 (d, J ¼ 0.6 Hz, 1 6 -H), 7.54 (d, J ¼ 8.4 Hz, 2ArH), 8.16
1
3
(
d, J ¼ 8.7 Hz, 2ArH) ppm; C NMR (75.48 MHz, CDCl ):
0 0
3 3
3
ꢂ ¼ 22.1, 23.2 (C-3 , C-4 ), 27.6 (CH ), 28.2 (CH ), 47.5
0
0
(Ar-CH), 49.6 (C-5), 65.3 (C-2 ), 105.2 (C-2), 110.2 (C-5 ),
[
[
[
0
1
1
23.49, 130.11 (ArC), 143.5 (C-6 ), 146.3, 147.0 (ArC), 163.9,
64.6 (C-4, C-6) ppm; MS (EI, 70 eV): m=z (%) ¼ 361 (4)
þꢅ
[M] , 303 (7), 277 (4), 275 (51), 218 (100.00), 143 (6), 84 (5).
Reactions of 5-Arylidene Derivatives of Meldrum’s Acid 1a–1c
with Cyanoacetic Acid Derivatives 7a and 7b
To a solution of 5 mmol 1a–1c and 6 mmol malononitrile
[22] Tietze LF, Stegelmeier H, Harms K, Brumby T (1982)
Angew Chem Int Ed Engl 21: 863
3
(7a, 0.40 g) or methyl cyanoacetate (7b, 0.60g) in 20 cm an-

4
88
A. Palasz et al.: 5-Arylidene Derivatives of Meldrum’s Acid
[
[
[
[
[
23] Tietze LF, Kiedrowski G (1981) Tetrahedron Lett 22:
19
24] Schuster P, Polansky OE, Wessely F (1964) Monatsh
Chem 95: 53
25] Bigi F, Carloni S, Ferrari L, Maggi R, Mazzacani A,
Sartori G (2001) Tetrahedron Lett 42: 5203
26] Kaupp G, Naimi-Jamal MR, Schmeyers J (2003) Tetra-
hedron 59: 3753
[28] Desai UV, Pore DM, Mane RB, Solabannavar SB,
Wadgaonkar PP (2004) Synth Commun 34: 25
[29] Xiang-Shan W, Zhao-Sen Z, Yu-Ling L, Da-Qing S, Shu-
Jiang T, Xian-Young W (2005) Synth Commun 35: 1915
[30] Wiles Ch, Watts P, Haswell SJ, Pombo-Villar E (2005)
Tetrahedron 61: 10757
[31] Davidson D, Bernhard SA (1948) J Am Chem Soc 70:
3426
[32] Gaulon C, Gizecki P, Dhal R, Dujardin G (2002) Synlett
6: 952
2
27] Ren Z, Cao W, Tong W, Jing X (2002) Synth Commun
3
2: 1947