Solvent-dependent reactivities of acyclic nitrones with β-diketones: Catalyst-free syntheses of endiones and enones

Article abstract of DOI:10.1016/j.tet.2012.06.086

Reactions of the nitrones ^-O⁺N(Me)C(H)Ar 1 (Ar=phenyl 1a, 4-methylphenyl 1b, 2,4,6-trimethylphenyl 1c, and anthracen-9-yl 1d) with the cyclic β-diketones 1,3-indandione 2 or barbituric acid 3 in CH ₂Cl₂, afford the corresponding endiones 2′a-2′d or 3′a-3′d. In contrast, dimedone 4 reacts with 1a or 1b to give the endione 4′a or 4′b and the bis-adduct 4″a or 4″b. Nevertheless, reaction of 4 with 1c or 1d in CH ₂Cl₂ furnishes only the endione adducts 4′c or 4′d. However, the reaction of 4 with 1a or 1b in methanol gives only 4″a or 4″b, respectively. Among acyclic β-diketones only malonic acid 7 reacts with 1a-1c. Reaction of 7 with 1a in CH₂Cl ₂ forms cinnamic acid 7″a, whereas in the case of 1b, the endione 7′b and (E)-3-p-tolylacrylic acid 7″b are obtained. The nitrone 1c reacts with 7 in CH₂Cl₂ to afford the endione 7′c or with acetone yielding (E)-4-mesitylbut-3-en-2-one 8. X-ray analyses are reported for 4′c, 5, and 7″b. In addition, the calculated acidity of the hydrogen at the α-C atom is shown to correlate with the reactivity of the β-diketones with nitrones.

Full text of DOI:10.1016/j.tet.2012.06.086

Tetrahedron 68 (2012) 7019e7027
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Solvent-dependent reactivities of acyclic nitrones with
syntheses of endiones and enones
b
-diketones: catalyst-free
,
a
,
c
a
,
b
,
a
Jamal Lasri a , Grzegorz Gajewski , M. Fatima C. Guedes da Silva
, Maxim L. Kuznetsov ,
*
*
ꢀ
Ricardo R. Fernandes a, Armando J.L. Pombeiro a
Centro de Química Estrutural, Complexo I, Instituto Superior Tecnico, Technical University of Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
,
*
a
ꢀ
b
ꢀ
Universidade Lusofona de Humanidades e Tecnologias, ULHT Lisbon, Av. Campo Grande no 376, 1749-024 Lisbon, Portugal
c Research Center for Applied Sciences, Academia Sinica, 128 Academia Road, Section 2, Nankang, 115-29 Taipei, Taiwan
a r t i c l e i n f o
a b s t r a c t
Reactions of the nitrones ꢀOþN(Me)]C(H)Ar
trimethylphenyl 1c, and anthracen-9-yl 1d) with the cyclic
1
(Ar¼phenyl 1a, 4-methylphenyl 1b, 2,4,6-
-diketones 1,3-indandione 2 or barbituric
Article history:
Received 10 March 2012
Received in revised form 15 June 2012
Accepted 21 June 2012
b
acid 3 in CH2Cl2, afford the corresponding endiones 20ae20d or 30ae30d. In contrast, dimedone 4 reacts
with 1a or 1b to give the endione 40a or 40b and the bis-adduct 400a or 400b. Nevertheless, reaction of 4
with 1c or 1d in CH2Cl2 furnishes only the endione adducts 40c or 40d. However, the reaction of 4 with 1a
Available online 28 June 2012
or 1b in methanol gives only 400a or 400b, respectively. Among acyclic
b-diketones only malonic acid 7
This paper is dedicated to the memory of
our wonderful colleague, Dr. Grzegorz
Gajewski, who recently passed away
reacts with 1ae1c. Reaction of 7 with 1a in CH2Cl2 forms cinnamic acid 700a, whereas in the case of 1b,
the endione 70b and (E)-3-p-tolylacrylic acid 700b are obtained. The nitrone 1c reacts with 7 in CH2Cl2 to
afford the endione 70c or with acetone yielding (E)-4-mesitylbut-3-en-2-one 8. X-ray analyses are re-
ported for 40c, 5, and 700b. In addition, the calculated acidity of the hydrogen at the
a-C atom is shown to
Keywords:
correlate with the reactivity of the b-diketones with nitrones.
b
-Diketones
Ó 2012 Elsevier Ltd. All rights reserved.
Acyclic nitrones
Endiones
Enones
1. Introduction
HClO4eSiO2.11 The Knoevenagel adducts, in fact, are useful in-
termediates for further transformations, such as DielseAlder and
Michael additions.12
The stereoselective synthesis of substituted olefins is an im-
portant aim in organic chemistry. The most general approach in-
volves elimination reactions, which, however, commonly give rise
to a mixture of double bond isomers with eventual predominance
of one of them (Zaytzev or Hofmann rules), and a high selectivity is
rare.1 The first effective methods for the selective synthesis com-
prise the Knoevenagel condensations,2 the McMurry,3 and Wittig4
reactions from aldehydes or ketones, which were shown to be ac-
celerated by microwave irradiation.5 Olefin metathesis provides
also powerful synthetic tools within both functionalized and
unfunctionalized olefins.6
The utilization of
b-diketones as starting materials for the
Knoevenagel condensation is, however, little explored.12,13 Very
likely, such compounds are less reactive than those traditionally
used, in view of their aptitude to form a stable cyclic enol. Very
recently, magnesium perchlorate14 or -proline15 was found to be
L
an efficient catalyst for the syntheses of trisubstituted functional-
ized alkenes via a Knoevenagel condensation between
and aldehydes.
b-diketones
In a previous work, we reported an unprecedented reaction of the
acidic -CH2 organonitriles NCCH2R, bearing an electron-
a
On the other hand, the classical Knoevenagel condensation is
carried out by reacting methylene active compounds bearing two
electron-withdrawing groups, such as malononitrile, cyanoace-
withdrawing substituent (R¼CO2Me, SO2Ph, COPh), with acyclic
nitrones, which constitutes a simple alternative method for the
preparation ofpure unsymmetricalcyano-functionalizedE-alkenes.16
Herein, we report an easy strategy for the syntheses of endiones
tates, malonates, and b-ketoesters, with aldehydes or ketones in the
presence of a base.2,7 The condensation can also be mediated by
and enones by reaction of acyclic nitrones with various b-diketones
Lewis acids such as TiCl4,8 ZnCl2,9 CeCl3$7H2OeNaI,10 and
(1,3-indandione, barbituric acid, dimedone, and malonic acid)
without any added catalyst or promoter. The reactions depend on
the solvent used as well as on the aryl substituent on the starting
* Corresponding authors. E-mail addresses: jamal.lasri@ist.utl.pt (J. Lasri), fati-
ma.guedes@ist.utl.pt (M.F.C. Guedes da Silva), pombeiro@ist.utl.pt (A.J.L. Pombeiro).
nitrone. In addition, the calculated acidity of the hydrogen at the a-
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.086

7020
J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
C atom is shown to correlate with the reactivity of the
with nitrones.
b
-diketones
5-arylidenepyrimidine-2,4,6(1H,3H,5H)-triones 30aed, as the only
products, in very good yields (Scheme 1, reaction b).
However, the reaction of dimedone 4 with the nitrone 1a
(Ar¼phenyl), under the above conditions for 2 h, gave a mixture of
2-benzylidene-5,5-dimethylcyclohexane-1,3-dione 40a and 2,20-
(phenylmethylene)-bis-(3-hydroxy-5,5-dimethylcyclohex-2-enone)
400a in a 1:4 ratio with 99% yield (Scheme 1, reaction c). The reaction
of 4 with the nitrone 1b (Ar¼4-methylphenyl), under the same
experimental conditions, also afforded a mixture of the Knoeve-
nagel product 40b and bis-adduct 400b in a 3:7 ratio with 98% yield.
The Knoevenagel products 40ae40b are highly reactive Michael
acceptors capable of engaging the unreacted CH acid reagent in
a kinetically rapid 1,4-addition to give the bis-adducts 400ae400b
(Scheme 2).12,17 The reaction of 4 with the nitrone 1a or 1b in
CH2Cl2, in a sealed tube at 80 ꢁC for 16 h, gave the same mixture of
products 40a/400a or 40b/400b in ratios similar to those indicated
above, that is, 1:4 or 3:7, respectively. Hence, there is no need of
extending the reaction time beyond 2 h.
2. Results and discussion
2.1. Reactions of nitrones with cyclic b-diketones
In the first part of the work, we focused our attention in the
catalyst-free reactions between acyclic nitrones 1 and various cyclic
b-diketones (1,3-indandione 2, barbituric acid 3, and dimedone 4)
bearing an acidic methylene moiety.
Hence, we studied the reactions of 1,3-indandione 2 with dif-
ferent acyclic nitrones ꢀOþN(Me)]C(H)Ar 1 (Ar¼phenyl 1a, 4-
methylphenyl 1b, 2,4,6-trimethylphenyl 1c, and anthracen-9-yl
1d) in CH2Cl2, in a sealed tube at 80 ꢁC for 2 h, and their progress
was monitored by TLC. The corresponding 2-arylidene-2H-indene-
1,3-diones 20aed were isolated as the exclusive products, in very
good yields, by column chromatography (CH2Cl2 as the eluent) and
obtained as pale yellow solids (Scheme 1, reaction a). Interestingly,
no reaction was observed at room temperature or under refluxing
CH2Cl2 at ambient pressure.
The reaction of dimedone 4 with the nitrone 1c (Ar¼2,4,6-
trimethylphenyl) or 1d (Ar¼anthracen-9-yl) also in CH2Cl2, in
a sealed tube at 80 ꢁC for 2 h, furnished the 5,5-dimethyl-2-(2,4,6-
O
O
O
2
Ar
(a)
O
2´a: Ar = C6H5 (85%)
2´b: Ar = 4-MeC6H4 (89%)
2´c: Ar = 2,4,6-Me3C6H2 (87%)
2´d: Ar = anthracen-9-yl (80%)
H
N
O
O
H
O
N
O
HN
Me
3
+
sealed tube
80 ºC, CH2Cl2
-MeNHOH
O
HN
N
-
(b)
Ar
O
O
Ar
1a: Ar = C6H5
1b: Ar = 4-MeC6H4
1c: Ar = 2,4,6-Me3C6H2
1d: Ar = anthracen-9-yl
3´a: Ar = C6H5 (79%)
3´b: Ar = 4-MeC6H4 (77%)
3´c: Ar = 2,4,6-Me3C6H2 (76%)
3´d: Ar = anthracen-9-yl (74%)
Me
Me
O
O
HO
Me
Me
O
O
Me
Me
4
Me
Me
+
(c)
Ar
OH
O
O
Ar
4´a: Ar = C6H5 (19%)
4´´a: Ar = C6H5 (79%)
4´b: Ar = 4-MeC6H4 (29%)
4´c: Ar = 2,4,6-Me3C6H2 (90%)
4´d: Ar = anthracen-9-yl (89%)
4´´b: Ar = 4-MeC6H4 (69%)
Scheme 1.
No evidence was found for the thermal decomposition of
the aryl nitrones 1 (to the corresponding aldehydes) under
our typical experimental conditions, and in fact the excess of
nitrone was isolated by column chromatography at the end of the
reaction.
trimethylbenzylidene)cyclohexane-1,3-dione 40c or the 2-(anthra-
cen-9-ylmethylene)-5,5-dimethylcyclohexane-1,3-dione 40d, re-
spectively, as the exclusive product (Scheme 1, reaction c), and no
bis-adducts were detected even after heating for an extended pe-
riod (16 h). These results suggest that formation of bis-adducts of
the type 400 should be essentially suppressed when using sterically
hindered arylnitrones such as 1c or 1d.
The reaction of barbituric acid 3 with the nitrones 1aed in
CH2Cl2, in a sealed tube at 80 ꢁC for 12 h, afforded the corresponding

J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
7021
Me
together with a small amount (ca. 5%) of the product of ring
cleavage (E)-1-mesityl-5,5-dimethylhex-1-en-3-one 40cc (with loss
of carbon monoxide) (Scheme 3).
Me
H
In contrast, the treatment of the pure adduct 40c in acetone, in
a sealed tube at 80 ꢁC for 12 h, showed that no decomposition of 40c
to other products was observed, and only the starting material was
recovered by column chromatography. However, reacting 40c with
N-methylhydroxylamine hydrochloride in acetone, in a sealed tube
at 80 ꢁC for 12 h, gave a very small amount of the reduced product
40cc (ca. 5e7%), supporting that the reductive ring cleavage of 40c
into 40cc is promoted by methylhydroxylamine, which conceivably
was oxidized to the corresponding nitroso compound.18 This re-
action with methylhydroxylamine should be performed with due
precautions in view of the risk of explosion associated to nitro-
methane formation.
O
Me
Me
HO
Ar
O
O
Dimerization
Me
Me
H
H
OH
O
O
4
Ar
O
4´a: Ar = C6H5
4´b: Ar = 4-MeC6H4
Me
Me
4´´a: Ar = C6H5
4´´b: Ar = 4-MeC6H4
Scheme 2.
However, the reaction of 1,3-indandione 2 with the nitrone 1c in
acetone, in a sealed tube at 80 ꢁC for 2 h, afforded 2-(propan-2-
ylidene)-2H-indene-1,3-dione 5 in 77% yield, as the only observed
product and no traces of 20c were detected (Scheme 4, reaction a).
We believe that the reaction was initiated by single deprotonation
of 2 by 1c to give the anionic basic form of the former, i.e.,
2.2. Effect of solvent in the reactions of nitrones with cyclic
b-diketones
We also investigated the solvent effect on the reactions of
nitrones with cyclic b-diketones.
δ
8.17
Me
Me
O
H
Me
Me
O
Me
Me
+
Me
N
-
O
Me
4´c (85%)
Me
Me
Me
O
1c
acetone
+
δ
7.70
O
sealed tube, 80 ºC, 12 h
-MeNHOH
(d, JHH = 16.6 Hz)
4
O
Me
Me
H
Me
Me
H
Me
Me
δ
6.36
(d, JHH = 16.6 Hz)
4´cc (5%)
Single isomer
Scheme 3.
Hence, the reaction of dimedone 4 with the nitrones 1a or 1b in
methanol, in a sealed tube at 80 ꢁC for 4 h, afforded only the bis-
adducts 400a or 400b, respectively, as the exclusive detected prod-
uct in ca. 80% yield (Scheme 2).
The reaction of dimedone 4 with acetone, in the absence of any
nitrone, gave the condensation product (5,5-dimethyl-2-(propan-
2-ylidene)cyclohexane-1,3-dione) in a very poor yield together
with a number of uncharacterized products, and the presence of the
adduct was confirmed by ESIþ-MS: m/z 181 [MþH]þ. Nevertheless,
the reaction of 4 with 1c in acetone, in a sealed tube at 80 ꢁC for 2 h,
furnished 40c as the exclusive product in very good yield (ca. 80%).
Curiously, the reaction of dimedone 4 with the nitrone 1c in
acetone, in a sealed tube at 80 ꢁC for 12 h, afforded the olefin 40c
RCOCHꢀCOR, which upon nucleophilic attack at the C]O carbon of
acetone (with elimination of one molecule of water), afforded ul-
timately 5. Furthermore, the reaction of 2 with acetone, in the
presence of N-methylhydroxylamine hydrochloride instead of the
nitrone 1c, also furnished 5 in 74% yield (Scheme 4, reaction b).
Alternatively, we performed the reaction of 2 with acetone, in
the absence of the nitrone 1c and N-methylhydroxylamine hydro-
chloride, and the condensation product 5 was also obtained, al-
though in a moderate yield (ca. 45%), but in this case the reaction
was slow and took at least 6 h (Scheme 4, reaction c). Moreover, the
reaction of barbituric acid 3 with acetone, without the nitrone 1c
and N-methylhydroxylamine hydrochloride, also afforded the
condensation product 6 in 87% yield (Scheme 4, reaction d).

7022
J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
The different behaviors displayed by 2e4 cannot be accounted
only on the basis of their different acidity (hydrogen at the -C
Me
+
Me
a
N
atom). In fact, for example, barbituric acid 3 has a much higher
acidic character than 1,3-indandione 2 or dimedone 4 (see theo-
retical part below), but required a longer reaction time, conceivably
due to its much lower solubility in acetone (reaction carried out
with a suspension).
-
O
Me
O
O
O
O
Me
Me
Me
1c
sealed tube
80 ºC, acetone, 2 h
77%
2.3. Reactions of nitrones with acyclic b-diketones
(a)
We also studied the catalyst-free reactions of the nitrones 1 with
various acyclic -diketones such as malonic acid 7, pentane-2,4-
dione 8, dibenzoylmethane 9, and N,N-dimethylacetoacetamide
10. Among all these acyclic -diketones, only malonic acid 7 reacted
5
2
b
MeNHOH.HCl
sealed tube, 80 ºC, acetone, 2 h
-H2O
b
with the nitrones 1ae1c in CH2Cl2, in a sealed tube at 80 ꢁC for 12 h,
and the products depend on the nitrone used. The reaction of the
nitrone 1a with malonic acid 7 afforded cinnamic acid 700a as the
only detected product, as a result of decarboxylation of the malonic
acid derivative (Scheme 5, reaction a). Using the nitrone 1b instead
of 1a, a mixture of 2-(4-methylbenzylidene)malonic acid 70b and
(E)-3-p-tolylacrylic acid 700b was obtained in the 1:1 ratio with 60%
yield (Scheme 5, reaction b). Moreover, in the case of the nitrone 1c,
only 2-(2,4,6-trimethylbenzylidene)malonic acid 70c was isolated,
without the decarboxylation product (Scheme 5, reaction c). De-
carboxylation of malonic acids was reported19 to occur in a micro-
wave autoclave, at an elevated reaction temperature and a high
power (190 ꢁC, 800 W).
74%
(b)
sealed tube, 80 ºC, acetone, 6 h
-H2O
45%
(c)
H
H
N
O
N
O
O
O
sealed tube
HN
HN
80 ºC, acetone, 12 h
Me
Me
Surprisingly, the reaction of malonic acid 7 with the nitrone 1c in
acetone, in a sealed tube at 80 ꢁC for 12 h, gave (E)-4-mesitylbut-3-
en-2-one 8 in 50% yield. Moreover, treatment of the nitrone 1c in
acetone, without malonic acid 7, under the same experimental
conditions, also afforded the product 8 in a similar yield (Scheme 6).
The formation of the (E)-4-mesitylbut-3-en-2-one 8 involves the
overall and formal removal of two acidic protons of acetone by the
-H2O
(d)
O
O
3
6 (87%)
Scheme 4.
Me
-
+
N
O
O
OH
1a
(a)
7´´a (57%)
Me
-
+
Me
N
O
O
Me
HO
OH
OH
sealed tube
1b
(b)
HO
OH
+
80 ºC, CH2Cl2
-MeNHOH
O
O
Me
O
O
7
7´b (29%)
7´´b (31%)
Me
-
Me
+
N
O
Me
Me
Me
Me
1c
Me
OH
(c)
HO
O
O
7´c (59%)
Scheme 5.

J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
7023
O
H
C
..
Me
-
H
Me
-
H
O
Me
+
C N
H
(a)
+
O
C
Me
+
H
sealed tube
H
Me
80 ºC, acetone, 12 h
Me
+
Me
Me
H
C N
1c
OH
Me
Me
(b)
O
C
δ
7.69
H
Me
(d, JHH = 16.5 Hz)
C H
O
Me
H
.
.
(c)
Me
H C N
Me
OH
Me
-MeNHOH
H
Me
Me
Me
δ
6.35
(d, JHH = 16.5 Hz)
Me
8 (50%)
Single isomer
Scheme 6.
{NOMe}2ꢀ fragment of the nitrone ꢀOþN(Me)]C(H)(2,4,6-
Me3C6H2), which thus undergoes N]C bond cleavage, with cou-
pling of the remaining acetone- and oxime-derived fragments to
afford 8. This unprecedented type of reaction is determined by the
Compound 8 was fully characterized and its spectroscopic data
compared with that previously reported.21
2.4. Acidity and reactivity
acidic character of the a-protons of acetone. A conceivable mecha-
nism is proposed in Scheme 6. The reaction is initiated by single
deprotonation of acetone by the nitrone 1c (step a) to give the anionic
basic form of the former, i.e., CH3C(]O)CHꢀ2 , which upon nucleo-
philic attack at the C]Nþ carbon of the cationic protonated nitrone
(CeC coupling, step b) forms 4-(N-hydroxy-N-methylamino)-4-
mesitylbutan-2-one as an intermediate. Abstraction of the second
proton from the 4-mesitylbutan-2-one fragment by the amine ni-
trogen with concomitant C]C bond formation and CeN bond
cleavage leads (step c) to the elimination of methylhydroxylamine
Me(H)NOH and the corresponding (E)-4-mesitylbut-3-en-2-one 8.
The olefins 20aed, 30aed, 40aed, 5, and 6 and the bis-adducts
400a and 400b þwere characterized by IR, 1H and 13C{1H} NMR spec-
troscopy, ESI -MS, elemental analyses and, for 40c and 5, also by
single-crystal X-ray structural diffraction analyses (Figs. 1 and 2,
respectively, see Experimental section). The C8eC9 ꢀb1ond distance
The experimental results described above indicate that the
acidity of the hydrogen at the
factors determining the reactivity of
nitrones. To verify this hypothesis, the pKa and
proton dissociation from the -C atom for the cyclic 2e4 and acyclic
a
-C atom may be one of the principal
-diketones in reactions with
G values of the
b
D
a
ꢁ
of 1.333(3) A and the IR bands at 1592 and 1613 cm assigned to
y
(C]C) in the spectrum of 40c, confirm the formation of the olefin.
The endiones 70be70c and enones (in this case acrylic acid de-
rivatives) 700ae700b were characterized by the above methods and,
for 700b, also by single-crystal X-ray diffraction structural analysis
(Fig. 3a, see Experimental section). The molecules of 700b are paired
by means of intermolecular OeH/O hydrogen bonds. According to
ꢁ
the distance [d(X/A), d(H/A)¼1.79, 2.6285(17) A] and angle
Fig. 1. Ellipsoid plot (arbitrary view) of 5,5-dimethyl-2-(2,4,6-trimethylbenzylidene)-
cyclohexane-1,3-dione 40c with atomic numbering scheme (ellipsoid probability level
of 30%) showing, in dotted lines, the weak non-classical intermolecular H-bond in-
teractions. Selected bond distances and angles, as well as d(D/A) and :(DeH/A) for
[:(XeH/A)¼173ꢁ] criteria20 this is the case of a strong interaction.
The paired molecules are layered and the cohesion of these layers is
achieved through a kind of van der Waals
p-stacking interaction
the H-bonds (A, ꢁ): C1eO1 1.218(3), C7eO2 1.206(3), C8eC9 1.333(3), C9eC10 1.476(3);
ꢁ
between the carboxylic groups and the aromatic rings of vicinal
molecules (Fig. 3b, see Experimental section).
C8eC9eC10 130.1(2), C7eC8eC1 118.4(2); C12eH12C/O2 [3.445(7), 161]. Symmetry
operations to generate equivalent atoms: (i) 1ꢀx,ꢀ1/2þy,1/2ꢀz; (ii) 1ꢀx,1/2þy, 1/2ꢀz.

7024
J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
Table 1
Calculated Gibbs free energy difference of deprotonation in gas
phase ( G in kcal/mol) and difference of pKa values in CH2Cl2
solution relative to the most acidic species
D
Ketone
D
G in gas phase
DpKa in CH2Cl2
2
3
4
7
331.7
321.7
331.0
322.8
329.1
336.4
334.9
346.6
4.7
0.0
3.8
0.5
1.3
6.2
6.4
14.0
PhC(O)CH2CN16
8
9
10
Fig. 2. Ellipsoid plot (arbitrary view) of 2-(propan-2-ylidene)-2H-indene-1,3-dione 5
with atomic numbering scheme (ellipsoid probability level of 50%) also showing, in
dotted lines, the weak non-classical intermolecular H-bond interactions. Selected bond
1a or 1b (bearing a phenyl or a 4-methylphenyl substituent)
in CH2Cl2, which furnish a mixture of Knoevenagel products
(endiones) and Michael adducts (dimmers), the use of sterically
hindered nitrones 1c or 1d (bearing 2,4,6-trimethylphenyl or
anthracen-9-yl substituents) can prevent the formation of
those dimmers, and the Knoevenagel products 2-arylidene-5,5-
distances and angles, as well as d(D/A) and :(DeH/A) for the H-bonds (A, ꢁ):
ꢁ
C1eO1 1.230(5), C8eO2 1.209(6), C9eC10 1.337(7); C10eC9eC1 127.9(5); C10eC9eC8
127.4(5); C12eH12C/O2 [3.445(7), 161]. Symmetry operations to generate equivalent
atoms: (i) ꢀx,1/2ꢀy,1/2ꢀz; (ii) x,1þy,z.
Fig. 3. (a) Ellipsoid plot viewed down the crystallographic c axis of (E)-3-p-tolylacrylic acid 700b with atomic numbering scheme (ellipsoid probability level of 50%) also showing, in
dotted lines, the intermolecular H-bond interactions. Selected bond distances and angles, as well as d(D/A) and :(DeH/A) for the H-bonds (A, ꢁ): C1eO1 1.300(4), C1eO2
ꢁ
1.2412(16), C2eC3 1.3346(18); O1eC1eO2 123.07(11); C1eC2eC3 122.88(12); O1eH1/O2 [2.6285(17), 173]. Symmetry operation to generate equivalent atoms: (i) 2ꢀx,1ꢀy,2ꢀz. (b)
Packing diagram (arbitrary view) of 700b showing in dotted lines the intermolecular H-bonds together with the
p
interactions (centroids are shown as dots) (3.592 A) between the
ꢁ
carboxylic groups and the aromatic rings.
RC(O)CH2C(O)R0 (R¼R0¼OH 7; R¼R0¼Me 8; R¼R0¼Ph 9; R¼Me,
dimethylcyclohexane-1,3-diones can be isolated as the exclusive
ones in very good yields.
R0¼NMe2 10)
b
-diketones and PhC(O)CH2CN16 were estimated for
the gas phase and CH2Cl2 solutions using the DFT/HF hybrid
method (B3LYP functional, see Computational details). The calcu-
lations demonstrate that b-diketones, which are inert toward the
reaction with acyclic nitrones (8, 9, and 10) bear the least acidic CH2
groups, while the most acidic species, 3, 7, and PhC(O)CH2CN,16 are
highly reactive (Table 1).
Other advantages of the reactions of dimedone with acyclic
nitrones include their simplicity, diversity, and possibility to lead to
different products (monomer and/or dimer) simply by varying the
aryl substituent of the starting nitrone and the solvent of the
reaction.
The reactions of 1,3-indandione or barbituric acid with acetone,
without any added Lewis acid or base catalyst, afforded the corre-
sponding condensation products (tetrasubstituted functionalized
alkenes) in moderate to good yields, respectively.
3. Conclusions
In conclusion, a catalyst-free strategy for the syntheses of
endiones (trisubstituted functionalized alkenes) and enones by
In contrast to the previous report22 on the Rh-catalyzed syn-
thesis of (E)-a,b-unsaturated carboxylic acids, the metal-free re-
reaction of acyclic nitrones with various
indandione, barbituric acid, dimedone, and malonic acid) was de-
veloped. In the case of the reactions of dimedone with the nitrones
b
-diketones (1,3-
action of malonic acid with nitrones gave (E)-3-(aryl)acrylic acids,
via decarboxylation of 2-(arylidene)malonic acids, and it represents
a simple and alternative route for the stereoselective syntheses of

J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
7025
acrylic acid derivatives. Nevertheless, the reaction of the nitrone 1c
with acetone gave (E)-4-mesitylbut-3-en-2-one 8 in a stereo-
selective fashion.
CHaromatic), 8.07e8.09 (m, 1H, CHaromatic), 8.12 (s, 1H, C]CH). 13C
{1H} NMR (CDCl3),
: 20.4 and 21.2 (CH3), 129.6 (C]CH), 123.3,
123.5, 128.4, 132.0, 135.2, 135.5, 136.9, 139.4, 140.6, 142.5 (Caromatic),
144.8 (C]CH), 188.4 and 189.5 (C]O). ESIþ-MS, m/z: 277 [MþH]þ.
Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.37; H, 5.55.
d
In addition, the calculated acidity of the hydrogen at the
a-C
atom is shown to correlate with the reactivity of the -diketones
b
with nitrones. Further expansion of the reaction scope and syn-
thetic applications of this methodology are in progress in our
laboratory.
4.2.4. 2-(Anthracen-9-ylmethylene)-2H-indene-1,3-dione
(20d). Yield 80%. IR (cmꢀ1): 1687 and 1720 (C]O), 1605 and 1629
(C]C). 1H NMR (CDCl3),
d
: 7.50e7.54 (m, 4H, CHaromatic), 7.81e7.90
(m, 3H, CHaromatic), 7.99e8.17 (m, 5H, CHaromatic), 8.60 (s,1H, C]CH),
8.93 (d, JHH 0.9 Hz, 1H, CHaromatic). 13C{1H} NMR (CDCl3),
: 129.9
4. Experimental section
4.1. General
d
(C]CH), 123.4, 123.6, 125.4, 125.5, 126.7, 126.8, 129.1, 130.4, 130.9,
133.9, 135.3, 135.6, 140.7, 142.6 (Caromatic), 141.7 (C]CH), 187.5 and
189.3 (C]O). ESIþ-MS, m/z: 335 [MþH]þ. Anal. Calcd for C24H14O2:
C, 86.21; H, 4.22. Found: C, 86.53; H, 4.29.
Solvents and reagents were obtained from commercial sources
and used as received. For TLC, silica gel plates with F-254 indicator
were used. 1H and 13C{1H} NMR spectra (in CDCl3 or DMSO-d6)
were measured on 300 or 400 MHz spectrometers at ambient
4.2.5. 5-Benzylidenepyrimidine-2,4,6(1H,3H,5H)-trione
temperature. 1H and 13C chemical shifts (
d) are expressed in parts
(30a).25 Yield 79%. IR (cmꢀ1): 1637 (C]C) and (C]O). 1H NMR
per million (ppm) relative to Si(Me)4. J values are in hertz (Hz).
Infrared spectra (4000e400 cmꢀ1) were taken from KBr pellets and
the wavenumbers are in cmꢀ1. Electrospray mass spectra were
carried out with an ion-trap instrument equipped with an elec-
trospray (ESI) ion source. The solutions in methanol were contin-
uously introduced into the mass spectrometer source with
(CDCl3),
omatic), 8.17 (s, 1H, C]CH). Due to the amido-imino tautomerism the
NH protons were not observed. 13C{1H} NMR (CDCl3),
: 132.0 (C]
CH), 127.0, 128.7, 129.9 (Caromatic), 150.4 (C]CH). Due to the amido-
imino tautomerism the C]O resonances were not observed even
after extended data collection. ESIþ-MS, m/z: 217 [MþH]þ. Anal.
Calcd for C11H8N2O3: C, 61.11; H, 3.73; N, 12.96. Found: C, 61.22; H,
3.90; N, 13.01.
d: 7.39e7.42 (m, 3H, CHaromatic), 7.58e7.62 (m, 2H, CHar-
d
a syringe pump at a flow rate of 10 mL/min. The drying gas tem-
perature was maintained at 350 ꢁC and dinitrogen was used as
nebulizer gas at a pressure of 35 psi. Scanning was performed from
m/z¼50 to 1500. Nitrones 1aed were prepared according to pub-
lished methods.16
4.2.6. 5-(4-Methylbenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
(30b).25 Yield 77%. IR (cmꢀ1): 1629 (C]O), 1515 (C]C). 1H NMR
(CDCl3),
d
: 2.39 (s, 3H, CH3Ph), AA0BB0 spin system [tolyl dA¼7.22
4.2. Reactions of
b
-diketones (1,3-indandione (2), barbituric
(2H), dB¼7.49 (2H)], 8.14 (s, 1H, C]CH). Due to the amido-imino
acid (3), and dimedone (4)) with acyclic nitrones LODN(Me)]
C(H)Ar (1) (Ar[C6H5 (1a), 4-MeC6H4 (1b), 2,4,6-Me3C6H2 (1c),
C6H4eC2HeC6H4 (1d)) in CH2Cl2
tautomerism the NH protons were not observed. 13C{1H} NMR
(CDCl3), d: 21.4 (CH3Ph), 129.2 (C]CH), 126.9, 129.5, 140.2 (Car-
omatic), 150.4 (C]CH). Due to the amido-imino tautomerism the C]
O resonances were not observed even after extended data collec-
tion. ESIþ-MS, m/z: 231 [MþH]þ. Anal. Calcd for C12H10N2O3: C,
62.60; H, 4.38; N, 12.17. Found: C, 62.77; H, 4.45; N, 12.01.
A solution of 1,3-indandione 2 (60.0 mg, 0.410 mmol) or a sus-
pension of barbituric acid 3 (60.0 mg, 0.468 mmol) or dimedone 4
(60.0 mg, 0.428 mmol) in CH2Cl2 (3.0 mL) was added at room
temperature to the appropriate nitrone 1 (1.2 equiv) and the mix-
ture was heated at 80 ꢁC in a sealed stainless steel tube for 2 h (in
the case of 2 and 4) or 12 h (in the case of 3) and the progress of the
reaction was monitored by TLC. After evaporation of the solvent in
vacuum to dryness, the crude residue was purified by column
chromatography on silica (CH2Cl2 as the eluent) followed by
evaporation of the solvent in vacuum to give the final products
20ae20d, 30ae30d, or 40ae40d and/or 400ae400b, respectively.
The reaction of 4 with 1a or 1b, in methanol at 80 ꢁC for 4 h,
leads to the formation of the dimmers 400a or 400b, respectively, as
the exclusive detected products with ca. 80% yield.
4.2.7. 5-(2,4,6-Trimethylbenzylidene)pyrimidine-2,4,6(1H,3H,5H)-
trione (30c). Yield 76%. IR (cmꢀ1): 1676 (C]O), 1591 (C]C). 1H NMR
(DMSO-d6),
CHaromatic), 8.31 (s, 1H, C]CH), 11.14, and 11.40 (two s, 2H, NH). 13
{1H} NMR (DMSO-d6),
: 20.7 and 21.6 (CH3Ph),132.3 (C]CH),123.3,
d: 2.07 (s, 6H, CH3Ph), 2.24 (s, 3H, CH3Ph), 6.86 (s, 2H,
C
d
128.5, 135.6, 138.2 (Caromatic), 151.2 (C]CH), 155.4, 161.7, and 163.4
(C]O). ESIþ-MS, m/z: 259 [MþH]þ. Anal. Calcd for C14H14N2O3: C,
65.11; H, 5.46; N, 10.85. Found: C, 65.32; H, 5.73; N, 10.91.
4.2.8. 5-(Anthracen-9-ylmethylene)pyrimidine-2,4,6(1H,3H,5H)-tri-
one (30d). Yield 74%. IR (cmꢀ1): 1641 and 1672 (C]O), 1541 and
1560 (C]C). 1H NMR (CDCl3),
d
: 7.46e7.64 (m, 4H, CHaromatic),
7.94e8.12 (m, 4H, CHaromatic), 8.29 (s, 1H, C]CH), 8.49 (s, 1H,
CHaromatic). 13C{1H} NMR (CDCl3),
: 129.4 (C]CH), 122.3, 125.1,
4.2.1. 2-Benzylidene-2H-indene-1,3-dione (20a). Yield 85%. The
obtained spectroscopic data are in accord with the literature data.23
d
125.5, 126.7, 128.8, 131.0, 132.7, 134.1 (Caromatic), 164.5, and 170.3
(C]O). The C]CH resonance was not observed even after extended
data collection. ESIþ-MS, m/z: 317 [MþH]þ. Anal. Calcd for
C19H12N2O3: C, 72.15; H, 3.82; N, 8.86. Found: C, 72.32; H, 3.53; N,
8.99.
4.2.2. 2-(4-Methylbenzylidene)-2H-indene-1,3-dione (20b).24 Yield
89%. IR (cmꢀ1): 1688 and1727 (C]O),1562,1589, and1620 (C]C).1H
NMR (CDCl3),
d
: 2.46 (s, 3H, CH3), AA0BB0 spin systems [tolyl dA¼7.34
(2H), dB¼8.41 (2H)], [o-disubstituted benzene dA¼7.82 (2H), dB¼8.02
(2H)]. 13C{1H} NMR (CDCl3),
d: 21.9 (CH3),130.6 (C]CH), 123.1, 123.2,
128.1, 129.6, 134.4, 135.0, 135.2, 139.9, 142.4, 144.6 (Caromatic), 147.1
(C]CH), 189.2, and 190.5 (C]O). ESIþ-MS, m/z: 249 [MþH]þ. Anal.
Calcd for C17H12O2: C, 82.24; H, 4.87. Found: C, 82.01; H, 4.95.
4.2.9. 2-Benzylidene-5,5-dimethylcyclohexane-1,3-dione (40a). Yield
19%. The obtained spectroscopic data are in accord with the liter-
ature data.26
4.2.3. 2-(2,4,6-Trimethylbenzylidene)-2H-indene-1,3-dione
4.2.10. 2,20-(Phenylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-
(20c). Yield 87%. IR (cmꢀ1): 1696 and 1732 (C]O), 1600 and 1636
2-enone) (400a).12b,c Yield 79%. IR (cmꢀ1): 1717 (C]O), 1594 (C]C).
(C]C). 1H NMR (CDCl3),
d: 2.25 (s, 6H, CH3), 2.35 (s, 3H, CH3), 6.96
1H NMR (CDCl3),
d: 1.12 (s, 6H, CH3C), 1.25 (s, 6H, CH3C), 2.36e2.45
(s, 2H, CHaromatic), 7.81e7.87 (m, 2H, CHaromatic), 7.95e7.97 (m, 1H,
(m, 8H, CH2), 5.56 (s, 1H, CHPh), 7.10e7.31 (m, 5H, CHaromatic), 11.91

7026
J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
(s, 2H, OH). 13C{1H} NMR (CDCl3),
d
: 27.4 and 29.7 (CH3C), 31.4
4.3.1. 2-(Propan-2-ylidene)-2H-indene-1,3-dione (5).28 Yield 77%. IR
(cmꢀ1): 1686 and 1720 (C]O), 1595 and 1620 (C]C). 1H NMR
(CCH3), 32.7 (CHPh), 46.4 and 47.1 (CH2), 115.6 (C]C), 125.8, 126.8,
128.2, 138.1 (Caromatic), 189.4 and 190.5 (C]O). ESIþ-MS, m/z: 369
[MþH]þ. Anal. Calcd for C23H28O4: C, 74.97; H, 7.66. Found: C, 75.09;
H, 7.37.
(CDCl3),
d
: 2.62 (s, 6H, CH3), AA0BB0 spin system [dA¼7.75 (2H),
dB¼7.91 (2H), coupling constants simulated by DFT:
JAB¼JB A ¼6.8 Hz, JAB ¼JBA ¼0.5 Hz, JAA ¼0.6 Hz, JBB ¼6.6 Hz]. 13C{1H}
0
0
0
0
0
0
NMR (CDCl3), d: 23.6 (CH3), 127.0 (C]CMe2), 122.8, 134.7, 140.8
4.2.11. 5,5-Dimethyl-2-(4-methylbenzylidene)cyclohexane-1,3-dione
(Caromatic), 170.2 (C]CMe2), 191.3 (C]O). ESIþ-MS, m/z: 187
[MþH]þ. Anal. Calcd for C12H10O2: C, 77.40; H, 5.41. Found: C, 77.59;
H, 5.53.
(40b). Yield 29%. IR (cmꢀ1): 1700 (C]O), 1597 (C]C). 1H NMR
(CDCl3),
7.21 (d, JHH 8.0 Hz, 2H, CHaromatic), 7.49 (d, JHH 8.0 Hz, 2H, CHaromatic),
8.13 (s, 1H, C]CH). 13C{1H} NMR (CDCl3),
: 21.4 (CH3Ph), 30.9
d: 1.08 (s, 6H, CH3C), 2.32 (s, 4H, CH2), 2.39 (s, 3H, CH3Ph),
d
4.3.2. 5-(Propan-2-ylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
(CH3C), 31.4 (CCH3), 45.9 and 46.4 (CH2), 129.4 (C]CH), 113.4, 126.9,
129.3, 140.1 (Caromatic), 150.3 (C]CH), 189.4 and 190.4 (C]O). ESIþ-
MS, m/z: 243 [MþH]þ. Anal. Calcd for C16H18O2: C, 79.31; H, 7.49.
Found: C, 79.15; H, 7.25.
(6). Yield 87%. IR (cmꢀ1): 1702 and 1749 (C]O), 1656 (C]C). 1H
NMR (CDCl3),
(CDCl3),
d
: 2.49 (s, 6H, CH3), 11.01 (s, 2H, NH). 13C{1H} NMR
d
: 27.8 (CH3), 118.2 (C]CMe2), 150.1 (C]CMe2), 163.8 and
177.3 (C]O). ESIþ-MS, m/z: 169 [MþH]þ. Anal. Calcd for C7H8N2O3:
C, 50.00; H, 4.80; N, 16.66. Found: C, 50.17; H, 4.99; N, 16.87.
4.2.12. 2,20-(p-Tolylmethylene)bis(3-hydroxy-5,5-dimethylcyclohex-
2-enone) (400b).27 Yield 69%. IR (cmꢀ1): 1717 (C]O), 1596 (C]C). 1H
4.4. Reactions of malonic acid (7) with acyclic nitrones
LODN(Me)]C(H)Ar (1) (Ar[C6H5 (1a), 4-MeC6H4 (1b), 2,4,6-
Me3C6H2 (1c)) in CH2Cl2
NMR (CDCl3), d: 1.12 (s, 6H, CH3C), 1.25 (s, 6H, CH3C), 2.20 (s, 3H,
CH3Ph), 2.35e2.45 (m, 8H, CH2), 5.53 (s, 1H, CHPh), AA0BB0 spin
system [tolyl dA¼7.00 (2H), dB¼7.10 (2H)], 11.92 (s, 2H, OH). 13C{1H}
NMR (CDCl3),
d: 20.8 (CH3Ph), 27.3 and 29.6 (CH3C), 31.7 (CCH3),
A suspension of malonic acid 7 (80.0 mg, 0.768 mmol) in CH2Cl2
(3.0 mL) was added at room temperature to the appropriate nitrone
1 (1.2 equiv), the mixture was heated at 80 ꢁC in a sealed stainless
steel tube for 12 h and the progress of the reaction was monitored
by TLC. After evaporation of the solvent in vacuum to dryness, the
crude residue was purified by column chromatography on silica
(CH2Cl2 as the eluent) followed by evaporation of the solvent in
vacuum to give the final products 700a, 70b and 700b or 70c.
32.4 (CHPh), 46.4 and 47.0 (CH2), 115.7 (C]C), 126.6, 128.9, 134.9,
135.2 (Caromatic),189.5 and 190.4 (C]O). ESIþ-MS, m/z: 383 [MþH]þ.
Anal. Calcd for C24H30O4: C, 75.36; H, 7.91. Found: C, 75.17; H, 7.57.
4.2.13. 5,5-Dimethyl-2-(2,4,6-trimethylbenzylidene)cyclohexane-1,3-
dione (40c). Yield 90%. IR (cmꢀ1): 1673 and 1712 (C]O), 1592 and
1613 (C]C). 1H NMR (CDCl3),
d
: 1.13 (s, 6H, CH3C), 2.13 (s, 6H,
CH3Ph), 2.31 (s, 3H, CH3Ph), 2.54 (s, 2H, CH2), 2.65 (s, 2H, CH2), 6.88
(s, 2H, CHaromatic), 8.17 (s, 1H, C]CH). 13C{1H} NMR (CDCl3),
: 20.2
d
4.4.1. Cinnamic acid (700a). Yield 57%. The obtained spectroscopic
and 21.1 (CH3Ph), 28.6 (CH3C), 29.8 (CCH3), 52.7 and 53.7 (CH2),
134.9 (C]CH), 128.1, 130.5, 131.6, 138.1 (Caromatic), 151.6 (C]CH),
196.5 and 197.4 (C]O). ESIþ-MS, m/z: 271 [MþH]þ. Anal. Calcd for
C18H22O2: C, 79.96; H, 8.20. Found: C, 80.03; H, 7.99.
data are in accord with the literature data.29
4.4.2. 2-(4-Methylbenzylidene)malonic acid (70b).30 Yield 29%. IR
(cmꢀ1): 1685 (C]C), 1769 (C]O). 1H NMR (CDCl3),
d: 2.39 (s, 3H,
CH3Ph), AA0BB0 spin system [tolyl dA¼7.22 (2H), dB¼7.48 (2H)], 8.15
4.2.14. 2-(Anthracen-9-ylmethylene)-5,5-dimethylcyclohexane-1,3-
(s, 1H, C]CH). 13C{1H} NMR (CDCl3),
d: 21.4 (CH3Ph), 129.1 (C]CH),
dione (40d). Yield 89%. IR (cmꢀ1): 1676 and 1711 (C]O), 1598 (C]
126.9, 129.5, 129.7, 140.3 (Caromatic), 150.1 (C]CH), 171.2 (C]O).
ESIþ-MS, m/z: 207 [MþH]þ. Anal. Calcd for C11H10O4: C, 64.07; H,
4.89. Found: C, 64.23; H, 4.76.
C). 1H NMR (CDCl3),
d: 1.20 (s, 6H, CH3C), 2.53 (s, 2H, CH2), 2.81 (s,
2H, CH2), 7.45e7.51 (m, 4H, CHaromatic), 7.72e7.84 (m, 2H, CHar-
omatic), 8.02e8.06 (m, 2H, CHaromatic), 8.48 (s,1H, C]CH), 8.91 (d, JHH
0.8 Hz, 1H, CHaromatic). 13C{1H} NMR (CDCl3),
d
: 28.6 (CH3C), 30.0
4.4.3. (E)-3-p-Tolylacrylic acid (700b). Yield 31%. The obtained
(CCH3), 52.8 and 53.6 (CH2), 130.9 (C]CH), 123.5, 124.9, 125.3,
126.2, 129.0, 131.0, 135.2, 137.1 (Caromatic), 148.9 (C]CH), 195.7 and
197.4 (C]O). ESIþ-MS, m/z: 329 [MþH]þ and 351 [MþNa]þ. Anal.
Calcd for C23H20O2: C, 84.12; H, 6.14. Found: C, 84.33; H, 6.23.
spectroscopic data are in accord with the literature data.31
4.4.4. 2-(2,4,6-Trimethylbenzylidene)malonic acid (70c). Yield 59%.
IR (cmꢀ1): 1626 (C]C), 1759 (C]O). 1H NMR (CDCl3),
d
: 2.31 (s, 3H,
CH3Ph), 2.40 (s, 6H, CH3Ph), 6.91 (s, 2H, CHaromatic), 8.44 (s, 1H, C]
CH). 13C{1H} NMR (CDCl3),
: 21.1 and 30.9 (CH3Ph), 128.6 (C]CH),
4.3. Reactions of 1,3-indandione (2) or barbituric acid (3) with
acetone
d
128.1, 129.3, 137.5, 138.8 (Caromatic), 150.0 (C]CH). The C]O reso-
nance was not observed even after extended data collection. ESIþ-
MS, m/z: 235 [MþH]þ. Anal. Calcd for C13H14O4: C, 66.66; H, 6.02.
Found: C, 66.56; H, 6.33.
A solution of 1,3-indandione 2 (60.0 mg, 0.410 mmol) or a sus-
pension of barbituric acid 3 (60.0 mg, 0.468 mmol) in acetone
(3.0 mL) was heated at 80 ꢁC in a sealed stainless steel tube for 6 h
(in the case of 2) or 12 h (in the case of 3) and the progress of the
reaction was monitored by TLC. In the case of 2, after evaporation of
the solvent in vacuum to dryness, the crude residue was purified by
column chromatography on silica (CH2Cl2 as the eluent) followed
by evaporation of the solvent in vacuum to give the final product 5.
In the case of 3, after evaporation of the solvent in vacuum to
dryness, the crude product was washed several times with diethyl
ether to give the final product 6 in good yield.
A moderate yield of 5 (ca. 45%) was obtained in the reaction of 2
with acetone, but the addition of 1.2 equiv of nitrone 1c (87.3 mg,
0.493 mmol) or N-methylhydroxylamine hydrochloride (41.2 mg,
0.493 mmol) to the initial reaction mixture leads to the formation
of 5 in a good yield (ca. 77 or 74%, respectively).
4.5. Reaction of malonic acid (7) with acyclic nitrone
LODN(Me)]C(H)(2,4,6-Me3C6H2) (1c) in acetone
A solution of malonic acid 7 (80.0 mg, 0.768 mmol) in acetone
(3.0 mL) was added at room temperature to the nitrone 1c
(163.3 mg, 0.922 mmol), the mixture was heated at 80 ꢁC in
a sealed stainless steel tube for 12 h and the progress of the reaction
was monitored by TLC. After evaporation of the solvent in vacuum
to dryness, the crude residue was purified by column chromatog-
raphy on silica (CH2Cl2 as the eluent) followed by evaporation of the
solvent in vacuum to give 8 as the exclusive product. The reaction of
1c with acetone, in the absence of malonic acid 7, also affords 8 in
similar yield.

J. Lasri et al. / Tetrahedron 68 (2012) 7019e7027
7027
4.5.1. (E)-4-Mesitylbut-3-en-2-one (8).21 Yield 50%. IR (cmꢀ1): 1610
(C]C),1682 (C]O). 1H NMR (CDCl3),
: 2.29 (s, 3H, CH3), 2.35 (s, 6H,
CH3Ph), 2.41 (s, 3H, CH3Ph), 6.35 (d, JHH 16.5 Hz, 1H, CH), 6.92 (s, 2H,
CHaromatic), 7.69 (d, JHH 16.5 Hz,1H, CH). 13C{1H} NMR (CDCl3),
: 21.1
(CH3Ph), 27.4 (CH3), 132.4 (CH]CHAr), 129.2, 130.8, 136.7, 138.5
(Caromatic), 142.0 (ArCH]CH), 198.5 (C]O). ESIþ-MS, m/z: 189
[MþH]þ. Anal. Calcd for C13H16O$1/4(H2O): C, 81.00; H, 8.63. Found:
C, 81.37; H, 8.69.
€
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Acknowledgements
~
This work has been partially supported by the Fundac¸ ao para
ˇ
a Ciencia e a Tecnologia (FCT), Portugal, and its PEst-OE/QUI/
UI0100/2011 project, PTDC/QUI-QUI/102150/2008 and PEst-OE/
QUI/UI0100/2011 projects. J.L. and M.L.K. express gratitude to the
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FCT and the ˇ Instituto Superior Tecnico (IST) for their research
contracts (Ciencia 2007 program). R.R.F. also thanks FCT for a fel-
lowship (grant SFRH/BD/31150/2006). The authors gratefully ac-
knowledge the Portuguese NMR Network (IST-UTL Center) for
access to the NMR facility. Thanks are also due to Dr. M.C. Vaz
(microanalytic service), Dr. C. Oliveira (ESI-MS) for the analytical
services, and Dr. Kamran Mahmudov for stimulating discussions.
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Supplementary data
Additional general information, X-ray crystallographic data for
compounds 40c, 5, and 700b, and computational details. CCDC ref-
erence numbers 816694e816696. Supplementary data associated
with this article can be found, in the online version, at doi:10.1016/
j.tet.2012.06.086.
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