Microwave-promoted Morita-Baylis-Hillman reactions: Efficient synthesis of new monoacylglycerols (MAGs) as potential anti-parasitic compounds

Article abstract of DOI:10.1590/s0103-50532011000900003

In this article we describe microwave irradiation promoting the synthesis of a hydrophilic monoacylglycerol, MAG, by hydrolysis of acrylate (15 min, 100%). After, MAG was transformed in hydrophilic Morita-Baylis-Hillman adducts (MBHA), (54-82%, pathway 1). In pathway 2, the different lipophilic MBHAs were prepared in high yields (90-100%) and transformed on hydrophilic MBHA, in 70-90%. Through the high temperature synthesis of one MBHA, a unprecedented indolizine formation was detected by GC-MS,. All results are in agreement with the new unified mechanism to the Morita-Baylis-Hillman reaction. These new monoacylglycerols, as well the its synthetic precursors, are new potential antiparasitic compounds. 2011 Sociedade Brasileira de Qui?mica.

Full text of DOI:10.1590/s0103-50532011000900003

J. Braz. Chem. Soc., Vol. 22, No. 9, 1634-1643, 2011.
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Article
A
Microwave-Promoted Morita-Baylis-Hillman Reactions: Efficient Synthesis of
New Monoacylglycerols (MAGs) as Potential Anti-Parasitic Compounds
Suervy C. O. Sousa, Claudio G. L. Junior, Fábio P. L. Silva, Natália G. Andrade,
Ticiano P. Barbosa and Mário L. A. A. Vasconcellos*
Departamento de Química, Universidade Federal da Paraíba, Campus I,
5
8059-900 João Pessoa-PB, Brazil
Descrevemos neste artigo, a irradiação por microondas promovendo a síntese de
monoacilglicerol hidrofílico, MAG, a partir da hidrólise de um acrilato (15 min, 100%). Depois,
o MAG foi transformado em adutos de Morita-Baylis-Hillman (AMBH) hidrofílicos, (54-82%,
caminho 1). No caminho 2, outros AMBHs foram preparados em altos rendimentos (90-100%)
e transformados em AMBH hidrofílicos em 70-90%. Durante e síntese em alta temperatura do
AMBH, foi detectado por CG-EM a formação de uma indolizina inédita. Todos estes resultados
estão de acordo com o novo mecanismo unificado para a reação de Morita-Baylis-Hillman.
Estes novos monoacilgliceróis, bem como seus precursores sintéticos, são novos compostos
antiparasitários em potencial.
In this article we describe microwave irradiation promoting the synthesis of a hydrophilic
monoacylglycerol, MAG, by hydrolysis of acrylate (15 min, 100%).After, MAG was transformed
in hydrophilic Morita-Baylis-Hillman adducts (MBHA), (54-82%, pathway 1). In pathway 2, the
different lipophilic MBHAs were prepared in high yields (90-100%) and transformed on hydrophilic
MBHA, in 70-90%. Through the high temperature synthesis of one MBHA, a unprecedented
indolizine formation was detected by GC-MS,. All results are in agreement with the new unified
mechanism to the Morita-Baylis-Hillman reaction. These new monoacylglycerols, as well the its
synthetic precursors, are new potential antiparasitic compounds.
Keywords: Morita-Baylis-Hillman reaction, microwaves, monoacylglycerols, acrylates,
potential antiparasitic
Introduction
most widely used (Scheme 1). The Morita-Baylis-Hillman
adducts (MBHA) have been extensively used as starting
materials in organic synthesis for a variety of applications,
The Morita-Baylis-Hillman reaction (MBHR) is an
1
,2
2
important way for C–C bond formation. It involves
the alkenes coupling containing electron-withdrawing
groups (EWG) with aldehyde, ketones or imines, among
others. Tertiary amines are used as nucleophilic catalysts
on which 1,4-diazabicyclo [2.2.2]octane (DABCO) is the
many of which have biological activity. An inconvenience
associated with this reaction is, in several examples, the
long reaction times. There are reports of reactions that, last
2
up to 65 days. However, due to the synthetic utility of these
MBHA adducts, several protocols have been described to
O
OH
NR (catalyst)
EWG
3
EWG
+
R
R
N
N
conditions
DABCO
R = alkyl, aryl, H
MBHA
EWG = CO R, CN, COR, others
2
Scheme 1. The general Morita-Baylis-Hillman reactions representation.
*
e-mail: mlaav@quimica.ufpb.br

Vol. 22, No. 9, 2011
Sousa et al.
1635
New MBHA
O
OH
OH O
O
X
X
Y
Z
W
O
HO
OH
Y
Z
OH
OH
OH
W
1
MAGs
8-13
2-7
Increased water
solubility
anti-leishmania
activities
Hydrosolubility
Scheme 2. 1: Glycerol; 2, 8: X =Y = Z = H, W = o-nitro; 3, 9: X =Y= Z = H, W = m-nitro; 4, 10: X =Y = Z = H, W = p-nitro; 5, 11: X = N,Y = Z = W = H;
, 12: Y = N, X = Z = W = H; 7, 13: Z = N, Y = X = W = H.
6
improve the reaction time and yields, such as the use of
ultrasound, high pressures, use of ionic liquids, change of
catalyst, change of solvents, microwaves irradiation, and
In this context we present in this article the design
and two efficient synthesis of new hydrophilic 8-13
1
5
monoacylglycerols (MAGs) (Scheme 2 and Figure 1)
idealized as potential anti-parasitic compounds.
2
several other experimental protocols.
Despite the fact that this reaction has already more than
0 years of existence, the debate on the exact mechanism
It has been reported in the literature that there is
an important relationship between the hydrophilicity-
lipophilicity and anti-parasitic activity of drugs, e.g., it
were described that increasing the solubility in water or
using cationic amphiphilic drugs (CADs) tends to increase
1
4
of reaction is still highlighted in the scientific community.
3
The first catalytic cycle suggested by Hill and Isaacs is
still accepted, but being the rate-determining step (RDS) it
remains at the center of the scientific debate. For example,
16
anti-leishmaniasis and anti-malarial activities. The strategy
presented here was based on the introduction of hydrophilic
portionderivedfromtheglycerol(1), asanimportantfactorin
water solubility increase of MBHA, previously described by
4
5
the nonprotic and protic currently accepted mechanisms
suggested by McQuade and Aggarwal respectively and
6
corroborated by Coelho have been very recently revisited
7
14
by Cantillo and Kappe.
us as anti-leishmania proprieties (Figure 1). The key step in
8
In our continuing search for bioactive substances
thesesynthesesistheMBHreactionbetweenthecommercial
aldehydes 14-19 (Figure 2) and the corresponding acrylates
20or21presentedinScheme3.AllMAGsstepspreparations
were promoted by microwave irradiations, a very efficient
and in connection with our efforts towards reactivity
9
of MBH reaction study, our research group described
in 2006 the molluscicidal activities of simple aromatic
17
MBHA against Biomphalaria glabrata (Say) snails,
and green methodology used to obtain improvement in
1
0
18
intermediate schistosomiasis host. In sequence, some
aromatic MBHA were presented as very active compounds
against the Leishmania amazonensis (cutaneous and
yields and rates of organic reactions.
Results and Discussion
1
1
mucocutaneous infections). Following that work,
we published the biological evaluation of aromatic
MBHA against Leishmania chagasi (visceral infections)
We began our experimental work on the acrylate
20 synthesis (Scheme 3). This compound was prepared
by reaction between acryloyl chloride and solketal on
1
2
parasites, and in 2010, we have shown that the MBHA
-hydroxy-2-methylene-3-(4-nitrophenyl)propanenitrile,
19
3
CH Cl at room temperature for 2 h (94%). The solketal
2 2
a high anti-leishmania compound, is also a highly active
compound against epimastigote and trypomastigote form
of Trypanosoma cruzi, the parasite that causes Chagas
is commercial, but it could easily be prepared here in 90%
yield, by heating to 60 °C of glycerol under azeotropic
distillation condition, on a mixture of acetone-pentane
1
3
19
disease. In the same year, we presented an improved
synthesis for sixteen MBHA and their biological
evaluation against L. amazonensis and L. chagasi
and we proposed, at the first time, a structure-activity
relationship (SAR) analysis for this class of anti-parasitic
(1:1) under p-toluenesulfonic acid catalysis. After that,
two synthetic pathways were investigated to MAGs 8-13
prepare (step iii and iv to pathway 1 and step v and vi to
pathway 2, Scheme 3).
There are up to now, more than 280 applications to
MAG 21 mainly for the polymers synthesis and other
1
4
compounds.

1
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Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
NO OH O
2
NO OH O
2
O
OH
O
OH
8
2
logP = 0.6ꢀ ± 0.ꢁ2
logP = 2.10 ± 0.ꢀ3
OH O
O
OH O
O N
2
O N
2
OH
O
OH
9
3
logP = 0.6ꢀ ± 0.ꢁ2
logP = 2.10 ± 0.ꢀ3
OH O
O
OH O
OH
O
OH
O N
2
O N
2
10
4
logP = 0.6ꢀ ± 0.ꢁ2
logP = 2.10 ± 0.ꢀ3
OH O
OH O
N
O
OH
N
O
OH
11
5
logP = −0.60 ± 0.ꢁ2
logP = 0.87 ± 0.ꢀ8
OH O
O
OH O
N
OH
N
O
OH
12
6
logP = −0.60 ± 0.ꢁ2
logP = 0.87 ± 0.ꢀ8
OH O
O
OH O
O
OH
N
OH
N
13
7
logP = −0.60 ± 0.ꢁ2
logP = 0.87 ± 0.ꢀ8
Figure 1. logP values were calculated in silico using the Pharma-algorithms®; help available from http://pharma-algorithms.com.
O
NO O
O
O
2
O
O
N
N
N
O N
2
NO2
15
1
4
16
17
18
19
1
1,12,14
Figure 2. Commercial aldehydes 14-19 used in this article, that were also used in our previous comunications.

Vol. 22, No. 9, 2011
Sousa et al.
1637
pathway 2
OH O
O
i, ii
X
Y
Z
W
O
O
HO
OH
O
O
O
OH
O
v
2
0
22-27
1
iii
vi
pathway 1
iv
OH O
O
X
Y
Z
W
O
OH
O
OH
OH
OH
21
8-13
Scheme 3. i) Glycerol/acetone-pentane (1:1), 60 °C, azeotropic distillation, 24 h, 95%; ii) solketal, 1.2 equiv. acryloyl chloride, CH Cl , TEA, 94%;
2
2
iii) acrylate 20, amberlyst 15, CH OH, MW, 60 °C, 15 min, 100%; iv) aldehydes 14-19, acrylate 21, 1 equiv. DABCO, conditions in Table 2, 54-82%;
3
v) aldehydes 14-19, acrylate 20, 1 equiv. DABCO, conditions in Table 3, 90-100%; vi) MBHA 22-27, condition in Table 4, 70-90%. 22, 8: X =Y = Z = H,
W = o-nitro; 23, 9: X = Y= Z = H, W = m-nitro; 24, 10: X = Y = Z = H, W = p-nitro; 25, 11: X = N, Y = Z = W = H; 26, 12: Y = N, X = Z = W = H; 27,
13: Z = N, Y = X = W = H.
2
0
macromolecules as nanoparticles. However, even that
Table 1. Conditions and results to MAG 21 preparation (Scheme 3,
pathway 1, step iii)
acrylates 20 and 21 are described, surprisingly, in the best
of our knowledge, only in 2008, Shi and co-workers
2
1
entry Condition
time Yields / (%)*
described a first procedure to MAG 21 synthesis directly
from the acrylate 20. Moreover, due to high water solubility
of 21 it is important the development of an experimental
protocol to 20→21 transformation using no large amount of
water or other very high boiling point polar solvent, aiming
to simplify this reaction isolation. Then, the development
of a more efficient technology to minimize this problem is
also an important point in this present article. First, to screen
the suitable reaction conditions using only water quantity
for the hydrolysis reaction of 20 in MAG acrylate 21 can
occur (step iii, Scheme 3), we investigated many protocols
o
1
2
3
4
Acetic acid 10%, 60 C
Acetic acid 10%, 0.01 equiv. BHT, 60 C 24 h
48 h
10
92
o
Amberlyst 15, CH OH, r.t.
4 h
97
3
Amberlyst 15, CH
OH, MW, 60 °C
15 min
100
3
*Isolated pure products. The compounds purities were evaluated from
GC-MS analysis.
2
7
97%). Very gratifying, we discover that the 21 yield
increased when the reaction was conducted in methanol
under microwave irradiation for 15 min without the addition
of any anti polymerization reagent. After that irradiation,
a simple filtration to remove the resin and evaporation of
methanol was necessary to obtained pure 21 in 100% yields
(entry 4, Table 1).
Continuing on the pathway 1, several conditions have
been evaluated on MBH reaction between the MAG acrylate
21 and aldehyde 14-19, modifying solvents (protic and
nonprotic), temperature, using the microwave irradiation,
trying to convert 21 to MBHA 8-13 (step iv, Scheme 3).
Again, the experimental protocol development to 21→8-13
transformation without the use of large amount of water
or other very high boiling point polar solvent, aiming to
simplify the isolation of these reactions, especially for the
more hydrophilic adducts 11, 12 and 13 (see the calculated
values of logP in Figure 1). In Table 2 we present our best
results for these steps iv.
22
as the use of PPTS/ CHCl / r.t. (24 h, no reaction), TsOH/
3
o
23
toluene/ 80 C (24 h, no reaction), TsOH/ CH OH/ r.t.
3
2
3
24
(
(
3 h, 34%), CHCl / FeCl .SiO / r.t (6h, 33%), HCl
3 3 2
2
5
catalytic)/ toluene/ r.t. (24 h, 16%), montmorillonite
KSF/ CHCl / 60 C (3 days, no reaction), montimorillonite
K10/ acetone/ 60 C (24 h, 51%) and amberlite IRA-120/
ethanol/78 C (24 h, 12%). In Fact, these previous results
to detach this transformation difficulty appears a simple
chemical processing.
o
26
3
o
26
o
26
After, we evaluated the use of acetic acid 10%, under
o
21
6
0 C (entry 1, Table 1, 10%). However, when this reaction
was carried out with addition of catalytic amount of BHT
as anti polymerizing compound we observed a very large
increase in the reaction yield (entry 2, Table 1, 92%).
However, the use of amberlyst 15 in methanol at room
temperature produced 21 in high yields (entry 3, Table 1,

1
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Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
Table 2. Results of the MBHA synthesis 8-13 from step iv in Scheme 3
1
mmol DABCO
OH O
O
Aldehyde (14-19)
X
Y
Z
O
OH
O
OH
MW, 100 °C
OH
OH
W
5
4-81%
2
1
8-13
entry
Aldehyde
MBHA
Solvent
time / min
Yields / (%)
1
2
3
4
5
6
14
15
16
17
18
19
8
CH CN
10
10
10
10
10
10
68
65
54
82
81
80
3
9
CH CN
3
10
11
12
13
CH CN
3
CH CN
3
CH CN
3
CH CN
3
*
1
8: X = Y = Z = H, W = o-nitro; 9: X = Y= Z = H, W = m-nitro; 10: X = Y = Z = H, W = p-nitro; 11: X = N, Y = Z = W = H; 12: Y = N, X = Z = W = H;
3: Z = N, Y = X = W = H.
Inthepathway2, theresultsofMBHreactionbetweenthe
reactions and then, there are not, up to now, a clear general
relationship between substrates-solvents-yields-rate, which
corroborates the unified mechanism proposed by Cantilo
less hydrophilic acrylate 20 and the aldehyde 14-19 (step v,
Scheme 3) were more efficient when they obtained from
step iv from pathway 1, considering both reactions under
microwave irradiations, producing the lipophilic MBHA
7
and Kappe for this exquisite reaction.
Completing the pathway 2 (step vi, Scheme 3), the
synthesis of adducts 8-13 from intermediates 22-27 was
first performed using the same methodology used on MAG
21 preparation (step iii, Scheme 3). However, surprisingly
these transformations were inefficient, showing low yield
(Table4, entry1). Sinceweobservednobyproductsfromthis
condition we have increased temperature (entry 2, Table 4).
However, we obtained low yield and, in this case, byproduct.
We believed that the origin of the principal byproduct could
be the result from Michael reaction between the Methanol (a
nucleophilic solvent) on 4-position of acrylate moiety from
2
2-27 in high yields (step v, 90%-100% yields, Table 3).
Again a complete study of different conditions was evaluated
and we present in Table 3 the best results obtained for each
evaluated adduct in this step. In this case, use of water or
high boiling point polar solvent media does not minimize
the reaction yield, since they are more lipophilic compounds.
We can point out that depending on the aldehydes
used in the MBH reaction can be obtained good yields
4
,6
5,6
in both protic or aprotic media, confirming that slight
changes in reaction conditions can change the RDS of these
Table 3. Results of the intermediates 22-27 preparations from the step v, presented in Scheme 3
Aldehyde (14-19)
OH O
O
X
1
equiv. DABCO
Y
Z
W
O
O
O
O
O
MW, 100 °C
O
9
0-100%
22-27
2
0
entry
MBHA
22
Aldehyde
Solvent
DMF
time / min
Yields / (%)
1
2
3
4
5
6
14
15
16
17
18
19
10
10
10
10
10
10
100
90
90
98
95
90
23
CH CN
3
24
DMF/H O*
2
25
CH CN
3
26
DMF/H O*
2
27
DMF/H O*
2
*
9:1 mixture of DMF/water; 22: X = Y = Z = H, W = o-nitro; 23: X = Y= Z = H, W = m-nitro; 24: X = Y = Z = H, W = p-nitro; 25: X = N, Y = Z = W =
H; 26: Y = N, X = Z = W = H; 27 = Z = N,Y = X = W = H.

Vol. 22, No. 9, 2011
Sousa et al.
1639
O
m/z = 235 [M+]
m/z = 144 (100%)
m/z = 116 (75%)
O
OH
OH
N
m/z = 162 (85%)
2
8
Figure 3. Indolizines 28, proposed as principal byproduct and characterized thought the expected fragmentations obtained by GC-MS.
adduct27beforeoralongwithadduct13production.Another
hypothesis suggested by us was the possibility of MBH
reaction reversibility using high temperature, according to
same experimental condition, compare the entries 3, 7 and
10, Table 4). This experimental observation also confirms
what has been discussed here about 2-N participation.
Finally, we believe that the best conversions to 8, 9 and
10 MAGs preparations compared with the conversions
in MAGs 11, 12 and 13 syntheses can be also explained
by the possibility of reversibility to the MBH reaction in
both protic and nonprotic media as proposed by Cantilo
7
the unified mechanism proposed by Cantillo and Kappe.
Based on these hypothesis we first investigated the solvent
change using t-butanol, which is less nucleophilic than
methanol, not changing microwave irradiation temperature.
In fact, this solvent change was efficient, producing the new
hydrophilic adduct 13 in good yield and no byproducts was
obtained (entry 3, Table 4). Continuing, this methodology
was high efficient to MAGs 8, 9 and 10 preparations from
MBHA 22, 23 and 24 (entries 4, 5 and 6, Table 4; step vi in
Scheme 3). In fact, Cantillo and Kappe described that the
MBH reaction between acrylates and nitroarylaldehyde are
less susceptible to reversibility even when high temperatures
7
and Kappe.
OH O
OH O
R
R
O
O
O
N
N
N
7
–OH
are used (until 107 °C the reaction is exergonic).
○
Reaction at 100 C of t-butanol on MBH adducts 25
O
O
(entry 7, Table 4), which presented a 2-piridinyl moiety,
R
R
O
lead to formation of two products, observed byTLC.A more
polar product was isolated on 58% yield and characterized
as the pure MAG 11 (entry 7, Table 4). The CGMS analysis
of the less polar product indicated that this supposed product
by TLC were in fact a more complex mixture of products
that were not possible to be isolated. However, in the largest
proportion byproduct (43% in this mixture) was proposed
to be the unpublished indolizine 28 (Figure 3). Since this
molecule could not be purified by flash chromatography,
no NMR data could were obtained and 28 preparation was
based on the CGMS data. This compound showed all the
N
H
H
28
Scheme 4. A proposal mechanism of reaction to 28 formation. R =
CH CH(OH) CH OH.
2
2
Table 4. Results of the MBHA 8-13 synthesis from step vi, presented
in Scheme 3
entry
MBHA
13
13
13
8
Solvent
T / °C
60
time /min Yields / (%)
1
2
3
4
5
6
7
8
9
CH OH
60
15
15
15
15
15
15
90
60
15
< 10
< 10*
70
3
28
CH OH
100
100
100
100
100
100
60
characteristic fragmentations (m/z) of the indolizine and
also all the expected fragmentations showed in Figure 3,
that no doubt characterizes the molecule 28. In fact, is
already well established in the literature that indolizines are
3
t-butanol
t-butanol
t-butanol
t-butanol
t-butanol
t-butanol
t-butanol
t-butanol
90
9
90
10
11
11
12
12
90
29
synthesizedathightemperatures. WepresentedinScheme4
a short proposal of mechanism reaction for the 28 formation.
As expected, the MAG 11 could be prepared in good
yield without byproducts formations by decreasing the
58**
70
60
40
1
*
0
100
70
o
temperature at 60 C (entry 8, Table 4). Then, it is clear
Byproducts were observed from chromatography, no identified.
that in lower temperature the addition of less nucleophilic
t-butanol solvent on 25 do not occurs and also the formation
of indolizines was not observed.
**Purified MAG 11 by chromatography.
Conclusions
It is important to detach that both reactions with adducts
presenting 3-pyridinyl (26) and 4-pyridinyl (27) moieties
give best yields than the reaction with the 25 adduct (in the
In summary we report in this article two efficient,
facile and quick synthesis of six new hydrophilic MBHA

1
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Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
8
-13 on high yield (pathway 2, 67-90% two steps-yields
slowly added. The reaction mixture kept under magnetic
stirring for 1 h at room temperature. Then the isolation was
done by adding the reaction mixture a solution of sodium
and pathway 1, 54-82% two steps-yields, Scheme 3) from
solketal acrylate 20. We also report a new very efficient
and quick synthesis of MAG 20 from 21 (100% yield),
using resin and microwave irradiation for 15 min.All steps
starting from acrylate 20 were performed under microwave
irradiation methodology.An advantage of pathway 2 is that
we can also produce a new more lipophilic MBHA 22-27
in high yields (90-100% one step from acrylate 20, step v,
Scheme 3). The bioactivities evaluations of these new 8-13
hydrophilic MAGs and also the new hydrophobic MBHA
bicarbonate NaHCO 10% and the product was extracted by
3
the organic phase (CH Cl ), which, in turn, was dried with
2
2
sodium sulfate anhydrous Na SO and concentrated under
2
4
reduced pressure where it was obtained a 94% isolated
1
yield. H NMR (CDCl , 200 MHz): d 1.38 (s, 3H), 1.41
3
(s, 3H), 3.71-4.41 (m, 5H), 5.84 (dd, 1H, J 10.2/1.6 Hz),
6.13 (dd, 1H, J 17.2/10.2 Hz), 6.43 (dd, 1H, J 17.2/1.6 Hz);
13
C NMR (CDCl , 50 MHz): d 29.3, 30.6, 68.7, 70.2, 77.5,
3
2
2-27 will continue with this present article.
113.8, 131.9, 135.4, 169.8.
21
Experimental
Synthesis of 2,3-dihydroxypropyl acrylate (21)
It was produced using 186 mg (1 mmol) of the
corresponding acrylate 20, 5 mL of methanol and 100 mg
of resin Amberlyst 15 that were placed in a 10 mL glass
microwave tube with magnetic stirrer. The reaction
tube was placed inside the cavity of a CEM Discover
benchmate and irradiated at 60 °C for 15 min. After the
reaction completes, the reaction mixture brought to room
temperature and was directly filtered using methanol
General
All commercially available reagents and solvent
were obtained from commercial providers and used
without further purification. Reactions were monitored
by TLC using silica gel 60 UV254 Macherey-Nagel
pre-coated silica gel plates; detection was by means of a
UV lamp. Flash column chromatography was performed
on 300-400 mesh silica gel. Organic layers were dried
over anhydrous MgSO or Na SO prior to evaporation
1
and concentrated in a rotary evaporator. H NMR
(CDCl , 200 MHz): d 3.39-4.71(m, 7H), 5.86(dd, 1H,
3
J 10.4/1.6 Hz), 6.13 (dd, 1H, J 17.2/10.4 Hz), 6.43 (dd,
4
2
4
1
3
on a rotary evaporator. Reactions requiring microwave
irradiation were performed in a microwave reactor CEM
1H, J 17.2/1.6 Hz); C NMR (CDCl , 50 MHz): d 67.2,
3
®
69.2, 74.0, 131.8, 135.8, 170.6.
model system Discover benchmate with temperature
1
13
monitored by built-in infrared sensor. H NMR and
C
A typical procedure for synthesis of 22-27 (Scheme 3)
NMR spectra were recorded usingVarian Mercury Spectra
1
13
AC 20 spectrometer (200 MHz for H, 50 MHz for C)
for adducts 22-27 together with the acrylates 20 and 21
acrylates and Bruker DPX300 spectrometer (300 MHz for
The corresponding aldehydes (1,5 mmol), 186 mg
(1 mmol) of acrylate 20, DABCO (1 equiv.) and 5 mL of
appropriate solvent were placed in a 10 mL glass microwave
tube with magnetic stirrer. The reaction tube was placed
1
13
H, 75 MHz for C) for the adducts 8-13. Chemical shifts
were reported relative to internal tetramethylsilane (d 0.00
ppm) for H, and CDCl (d 77.0 ppm) for C. FTIR spectra
were recorded on a Shimadzu spectrophotometer model
IRPrestige-21 in KBr pellets. MS data were measured
with a Shimadzu GCMS-QP2010 mass spectrometer. High
resolution mass spectra were determined using a MicroTOF
®
inside the cavity of a CEM Discover benchmate and
1
13
irradiated at 100 °C for 10 min.After the reaction completes,
the reaction mixture brought to room temperature where the
solvent used were extracted from the reaction medium and
the product was isolated from the crude reaction by column
chromatography through silica gel, using AcOEt:hexane as
solvent at a ratio of 3:7 to the adducts 22, 23 and 24 and 7:3
to the adducts 25, 26 and 27. The reaction products were
concentrated under reduced pressure and characterized by
NMR, IR and mass spectroscopy.
3
®
Ic Bruker Daltonics spectrometer . Solketal were prepared
in this work as described in Results and Discussion section
and characterized in accordance with the commercial
compounds physical data.
21
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl acrylate (20)
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxy(2-
The reaction was performed using solketal 6 g
0.045 mols) which was left under stirring at 0 °C with
nitrophenyl)methyl)] acrylate (22)
1
(
H NMR (CDCl , 200 MHz): d 1.31 (s, 3H), 1.38 (s,
3
8
0 mL of dichloromethane (CH Cl ) and 7 mL of TEA
3H), 3.60-4.34 (m, 6H), 5.70 (d, 1H, J 5.8 Hz), 6.20 (s, 1H),
6.38 (s, 1H), 7.45 (m, 1H), 7.63 (t, 1H, J 7.8 Hz), 7.75 (d,
1H, J 8.0 Hz), 7.94 (d, 1H, J 8.0 Hz); C NMR (CDCl ,
3
2
2
in a closed system. After 5 min, a solution containing
0 mL of CH Cl and 4.8 mL of acryloyl chloride was
13
2
2
2

Vol. 22, No. 9, 2011
Sousa et al.
1641
5
1
0 MHz): d 29.1, 30.5, 69.5, 70.0, 71.1, 77.2, 113.8, 128.5,
1716, 1145, 1060; ESI-HRMS (m/z) calc. for C H NO
15 19 5
[(M+H) ] 294.1296, found 294.1337.
+
30.9, 132.6, 132.8, 137.5, 140.3, 144.8, 152.1, 169.4;
-1
IR (KBr) νmax/cm : 3433, 2989, 2939, 2889, 1724, 1527,
350, 1157, 1053; ESI-HRMS (m/z) calc. for C H NO
7
1
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl
1
6
19
+
[(M+H) ] 338.1195, found 338.1233.
(pyridin-4-yl)methyl)] acrylate (27)
1
H NMR (CDCl , 200 MHz): d 1.34 (s, 3H), 1.39 (d,
3
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl(3-
3H, J 4.2 Hz), 3.63-4.35 (m, 6H), 5.55 (s, 1H), 5.96 (d,
1H, J 4.6 Hz), 6.44 (s, 1H), 7.33 (d, 2H, J 6 Hz), 8.46 (d,
nitrophenyl)]methyl) acrylate (23)
1
13
H NMR (CDCl , 200 MHz): d 1.34 (s, 3H), 1.40 (d,
2H, J 4.8); C NMR (CDCl 50 MHz): d 29.1, 30.6, 69.0,
3
3
3
6
7
H, J 4.0 Hz), 3.65-4.37 (m, 6H), 5.67 (d, 1H, J 4.6 Hz),
.01 (d, 1H, J 5.2 Hz), 6.47 (s, 1H), 7.52 (t, 1H, J 7.8 Hz),
.75 (d, 1H, J 7.6 Hz), 8.15 (d, 1H, J 8.0 Hz), 8.27 (s, 1H);
69.9, 75.5, 77.2, 113.8, 125.5, 131.6, 145.0, 153.4, 155.1,
-1
169.4; IR (KBr) νmax/cm : 3140, 2989, 2877, 1716, 1141,
+
1056; ESI-HRMS (m/z) calc. for C H NO [(M+H) ]
1
5
19
5
13
C NMR (CDCl 50 MHz): d 29.1, 30.6, 69.1, 69.9, 75.9,
294.1296, found 294,1337.
3
7
1
1
7.2, 113.8, 125.7, 126.6, 131.4, 133.2, 136.8, 145.1, 147.9,
52.2, 169.4; IR (KBr) νmax/cm :3437, 2989, 2935, 2889,
-1
A typical procedure for synthesis of MAGs 8-13 from step
iv (Scheme 3)
716, 1531, 1350, 1157, 1053; ESI-HRMS (m/z) calc. for
+
C H NO [(M+H) ] 338.1195, found 338.1239.
1
6
19
7
The corresponding aldehydes (1.5 mmol), 146 mg
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl(4-
(1 mmol) of acrylate 21, DABCO (1 equiv.) and 5 mL of
nitrophenyl)methyl)] acrylate (24)
acetonitrile(CH CN)wereplacedina10mLglassmicrowave
3
1
H NMR (CDCl , 200 MHz): d 1.31 (s, 3H), 1.36 (d,
tubewithmagneticstirrer.Thereactiontubewasplacedinside
the cavity of a CEM Discover benchmate and irradiated at
100 °C for 10 min. After the reaction completes, the reaction
3
3
1
H, J 4.0 Hz), 3.62-4.33 (m, 5H), 4.44 (sl, 1H), 5.64 (d,
H, J 4.2 Hz), 5.97 (d, 1H, J 4.8 Hz), 6.41 (s, 1H), 7.55
13
(d, 2H, J 8.4 Hz), 8.15 (d, 2H, J 8.6 Hz); C NMR (CDCl
mixture brought to room temperature where the CH CN was
3
3
5
1
0 MHz): d 29.1, 30.6, 70.0, 69.9, 75.5, 77.2, 113.8,
27.4, 131.2, 131.5, 145.3, 151.2, 153.2, 169.4; IR (KBr)
extracted from the reaction medium and the product was
isolated from the crude reaction by column chromatography
through silica gel, using AcOEt:hexane as solvent at a ratio
of 8:2 to the adducts 8, 9 and 10 and using MeOH:AcOEt
as solvent at a ratio of 1:9 to the adducts 11, 12 and 13. The
reaction products were concentrated under reduced pressure
and characterized by NMR, IR and mass spectroscopy.
-
1
νmax/cm : 3410, 3213, 2985, 2935, 2897, 1716, 1519,
350, 1157, 1056; ESI-HRMS (m/z) calc. for C H NO
1
1
6
19
7
+
[(M+H) ] 338.1195, found 338.1229.
(
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxy
pyridin-2-yl)methyl)] acrylate (25)
1
H NMR (CDCl , 200 MHz): d 1.30 (s, 3H), 1.36 (d,
A typical procedure for synthesis of MAGs 8-13 from step
3
3
1
1
H, J 3.8 Hz), 3.59-4.28 (m, 5H), 4.98 (sl, 1H), 5.59 (s,
H), 5.97 (s, 1H), 6.38 (s, 1H), 7.18 (m, 1H), 7.40 (d,
H, J 8.0 Hz), 7.65 (td, 1H, J 7.6/1.6 Hz), 8.49 (dd, 1H,
vi (Scheme 3)
The corresponding MBHA 22-27 (1.0 mmol), 5.0 mL
of t-butanol and 100 mg of resinAmberlyst 15 were placed
in a 10 mL glass microwave tube with magnetic stirrer.
The reaction tube was placed inside the cavity of a CEM
1
3
J 4.8/1.0 Hz); C NMR (CDCl 50 MHz): d 29.2, 30.6,
3
6
1
2
8.7, 70.2, 76.0, 77.2, 113.7, 125.2, 126.6, 131.5, 140.8,
-1
45.4, 152.1, 163.4, 169.8; IR (KBr) νmax/cm :3421, 2985,
®
939, 2889, 1720, 1157, 1053; ESI-HRMS (m/z) calc. for
Discover benchmate and irradiated at 100 °C for 15 min
+
C H NO [(M+H) ] 294.1296, found 294.1335.
(except for the adduct 25 which was irradiated at 60 °C
for 90 min to get to 11). After the reaction completes, the
reaction mixture brought to room temperature and was
directly filtered using methanol as solvent and concentrated
under reduced pressure. The reaction products were isolated
from the crude reaction by column chromatography through
silica gel usingAcOEt:hexane as solvent at a ratio of 8:2 to
the adducts 8, 9 and 10 and using MeOH:AcOEt as solvent
at a ratio of 1:9 to the adducts 11, 12 and 13. The reaction
products were concentrated under reduced pressure and
compared by TLC with those obtained in the step iv.
1
5
19
5
(
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2(hydroxyl
pyridin-3-yl)methyl)] acrylate (26)
1
H NMR (CDCl , 200 MHz): d 1.32 (s, 1H), 1.38 (d,
3
1
1
7
1
6
1
H, J 3.2 Hz), 3.58-4.33 (m, 6H), 5.59 (s, 1H), 6.02 (d,
H, J 3.4 Hz), 6.43 (s, 1H), 7.25 (dd, 1H, J 8.0/5.0 Hz),
.72 (d, 1H, J 8.0 Hz), 8.38 (d, 1H, J 4.6 Hz), 8.47 (d,
1
3
H, J 2.0 Hz); C NMR (CDCl 50 MHz): d 29.1, 30.6,
3
9.9, 70.0, 74.3, 77.2, 113.8, 127.4, 130.7, 141.5, 145.4,
-1
52.3, 152.5, 169.4; IR (KBr) νmax/cm : 3124, 2989, 2877,

1
642
Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
+
The MAGs 8-13 spectroscopic data
,3-Dihydroxypropyl[2-(hydroxyl(2-nitrophenyl)methyl)]
ESI-HRMS (m/z) calc. for C H NO [(M+H) ] 254.0983,
found 254.1021.
12
15
5
2
acrylate (8)
2,3-Dihydroxypropyl[2-(hydroxyl(pyridin-3-yl)methyl)]
1
H NMR (MeOD, 300 MHz): d 3.35 (s, 3H), 3.46-3.55
acrylate (12)
1
(
(
7
m, 2H), 3.79-3.86 (m, 1H), 4.13-4.23 (m, 2H), 5.72-5.74
m, 1H), 6.26 (s, 1H), 6.37 (s, 1H), 7.48-7.54 (m, 1H),
.66-7.72 (m, 1H), 7.77 (d, 1H, J 7.8 Hz), 7.94 (d, 1H,
H NMR (MeOD, 300 MHz): d 3.35 (s, 2H), 3.47-
3.67 (m, 3H), 3.75-3.83 (m, 1H), 4.07 (ddd, 1H,
J 11.4/6.0/4.2 Hz), 4.17 (ddd, 1H, J 11.4/4.5/2.4 Hz), 5.64
(s, 1H), 6.15 (s, 1H), 6.46 (d, 1H, J 1.2 Hz), 7.40 (ddd, 1H,
J 7.8/4.8/0.6 Hz), 7.84 (dt, 1H, J 8.1/1.8 Hz), 8.43 (dd, 1H,
1
3
J 8.1 Hz); C NMR (MeOH, 75 MHz): d 64.2, 67.0, 67.6,
7
1
1
1.1, 124.5, 126.4, 129.3, 129.8, 134.3, 138.4, 144.2,
-1
13
67.1; IR (KBr) νmax/cm : 3383, 1712, 1527, 1350, 1265,
157, 1120, 1045; ESI-HRMS (m/z) calc. for C H NO
J 4.8/1.5 Hz), 8.56 (d, 1H, J 1.8 Hz); C NMR (MeOH,
75 MHz): d 64.1, 67.0, 70.9, 71.1, 125.1, 126.2, 137.0,
13
15
7
+
-1
[
(M+Na) ] 320.0746, found 320.0748.
140.3, 144.1, 149.2, 149.4, 167.0; IR (KBr) νmax/cm :3348,
1
716, 1265, 1157, 1118, 1029; ESI-HRMS (m/z) calc. for
+
2
,3-Dihydroxypropyl[2-(hydroxyl(3-nitrophenyl)methyl)]
C H NO [(M+H) ] 254.0983, found 254.1023.
12
15
5
acrylate (9)
1
H NMR (MeOD, 300 MHz): d 3.35 (s, 2H), 3.49
2,3-Dihydroxypropyl[2-(hydroxyl(pyridin-4-yl)methyl)]
(
d, 2H, J 5.4 Hz), 3.75-3.83 (m, 1H), 4.07 (ddd, 1H,
J 11.4/6.0/4.2 Hz), 4.17 (ddd, 1H, J 11.4/4.5/3.0 Hz),
.70 (s, 1H), 6.13 (dd, 1H, J 2.1/1.5 Hz), 6.46 (dd, 1H,
J 2.4/1.2 Hz), 7.56 (t, 1H, J 8.1 Hz), 7.77-7.81 (m, 1H),
acrylate (13)
1
H NMR (MeOD, 300 MHz): d 3.35 (s, 3H), 3.49-3.60
(m, 2H), 3.77-3.83 (m, 1H), 4.06-4.21 (m, 2H), 5.61 (s, 1H),
6.08 (dd, 1H. J 2.5/1.0 Hz), 6.45 (dd, 1H, J 2.0/1.0 Hz), 7.47
(d, 2H, J 6.5 Hz), 8.47 (dd, 2H, J 4.5/1.5 Hz); C NMR
(MeOH, 75 MHz): d 64.1, 64.6, 71.1, 71.8, 123.7, 127.0,
5
1
3
8
.13 (ddd, 1H, J 8.1/2.1/0.9 Hz), 8.26 (t, 1H, J 1.8 Hz);
C NMR (MeOH, 75 MHz): d 64.1, 67.0, 71.1, 72.2, 123.0,
23.5, 126.5, 130.6, 134.6, 144.3, 146.4, 149.7, 167.0; IR
13
-1
1
143.9, 150.0, 167.0; IR (KBr) νmax/cm :3363, 1716, 1269,
1161, 1115, 1053; ESI-HRMS (m/z) calc. for C H NO
-1
(KBr) νmax/cm :3375, 1708, 1527, 1350, 1273, 1157, 1095,
12
15
5
+
+
1
049; ESI-HRMS (m/z) calc. for C H NO [(M+Na) ]
[(M+H) ] 254.0983, found 254.1027.
1
3
15
7
3
20.0746, found 320.0749.
Supplementary Information
2
,3-Dihydroxypropyl[2-(hydroxyl(4-nitrophenyl)methyl)]
acrylate (10)
Supplementary data are available free of charge at
http://jbcs.sbq.org.br as a PDF file.
1
H NMR (MeOD, 300 MHz): d 3.35 (s, 2H), 3.47-3.51
(m, 3H), 3.75-3.82 (m, 1H), 4.04-4.21 (m, 2H), 5.69 (s, 1H),
6
7
.10 (dd, 1H, J 2.1/1.5 Hz), 6.44 (dd, 1H, J 2.1/0.9 Hz),
.63 (d, 2H, J 9.0 Hz), 8.19 (d, 2H, J 9.0 Hz); C NMR
Acknowledgments
13
(
1
MeOH, 75 MHz): d 64.1, 67.0, 71.1, 72.3, 124.5, 126.6,
29.3, 138.4, 144.2, 148.9, 167.0; IR (KBr) νmax/cm :3375,
This work has been supported by CNPq, CAPES and
FAPESQ-PB.
-1
1
708, 1519, 1350, 1269, 1157, 1111, 1049; ESI-HRMS
+
(
m/z) calc. for C H NO [(M+Na) ] 320.0746, found
References
1
3
15
7
3
20.0749.
1
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2
,3-Dihydroxypropyl[2-(hydroxy(pyridin-2-yl)methyl)]
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1
H NMR (MeOD, 300 MHz): d 3.349 (s, 2H), 3.470-
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(
(
(
1
3
1
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Figueiredo, L. R. F.; Souza, S. C. O.; Batista, G. N.; Silva,T. G.;
Silva, T. M.; Oliveira, M. R.; Vasconcellos, M. L. A. A.; Eur. J.
Med. Chem. 2009, 44, 1726.
29. Basavaiah, D.; Devendar, B.; Lenin, D. V.; Satyanarayana,
T.; Synlett 2009, 411; Jiang, M.; He, Q.; Yang, C.; Xie, Y.;
Heterocycles 2008, 75, 2659; Basavaiah, D.; Rao, A.; J. Chem.
Commun. 2003, 604; Basavaiah, D.; Rao, A. J.; Tetrahedron
Lett. 2003, 44, 4365; Bode, M. L.; Kaye, P. T. J.; Chem. Soc.,
Perkin Trans. 1 1993, 180.
1
1
3. Sandes, J. M.; Borges, A. R.; Junior, C. G. L.; Silva, F. P. L.
Carvalho, G. A. U.; Rocha, G. B.; Vasconcellos, M. L. A. A.;
Figueiredo, R. C. B. Q.; Bioorg. Chem. 2010, 38, 190.
4. Junior, C. G. L.; de Assis, P. A. C.; Silva, F. P. L.; Sousa, S. C.
O.; Andrade, N. G.; Barbosa, T. P.; Nerís, P. L. N.; Segundo, L.
V. G.; Anjos, I. C.; Carvalho, G. A. U.; Rocha, G. B.; Oliveira,
M. R.;Vasconcellos, M. L.A.A.; Bioorg. Chem. 2010, 38, 279.
Submitted: January 31, 2011
Published online: June 2, 2011

J. Braz. Chem. Soc., Vol. 22, No. 9, S1-S41, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0
103 - 5053 $6.00+0.00
Supplementary Information
SI
Microwave-Promoted Morita-Baylis-Hillman Reactions: Efficient Synthesis of
New Monoacylglycerols (MAGs) as Potential Anti-Parasitic Compounds
Suervy C. O. Sousa, Claudio G. L. Junior, Fábio P. L. Silva, Natália G. Andrade,
Ticiano P. Barbosa and Mário L. A. A. Vasconcellos*
Departamento de Química, Universidade Federal da Paraíba, Campus I,
5
8059-900 João Pessoa-PB, Brazil
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl acrylate (20)
1
H NMR (CDCl , 200 MHz): d 1.38 (s, 3H), 1.41 (s, 3H), 3.71-4.41 (m, 5H), 5.84 (dd, 1H, J 10.2/1.6 Hz), 6.13 (dd,
3
13
1
1
H, J 17.2/10.2 Hz), 6.43 (dd, 1H, J 17.2/1.6 Hz); C NMR (CDCl 50 MHz): d 29.3, 30.6, 68.7, 70.2, 77.5, 113.8, 131.9,
3
35.4, 169.8.
13
Figure S1. C NMR spectrum of compound 20.
*e-mail: mlaav@quimica.ufpb.br

S2
Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
1
Figure S2. H NMR spectrum of compound 20.
1
Figure S3. H NMR spectrum of compound 20.

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S3
2,3-Dihydroxypropyl acrylate (21)
1
H NMR (CDCl , 200 MHz): d 3.39-4.71(m, 7H), 5.86(dd, 1H, J 10.4/1.6 Hz), 6.13 (dd, 1H, J 17.2/10.4 Hz), 6.43 (dd,
3
1
3
1
H, J 17.2/1.6 Hz); C NMR (CDCl 50 MHz): d 67.2, 69.2, 74.0, 131.8, 135.8, 170.6.
3
13
Figure S4. C NMR spectrum of compound 21.
1
Figure S5. H NMR spectrum of compound 21.

S4
Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
1
Figure S6. H NMR spectrum of compound 21.
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxy(2-nitrophenyl)methyl)] acrylate (22)
1
H NMR (CDCl , 200 MHz): d 1.31 (s, 3H), 1.38 (s, 3H), 3.60-4.34 (m, 6H), 5.70 (d, 1H, J 5.8 Hz), 6.20 (s, 1H), 6.38 (s,
3
13
1
3
2
H), 7.45 (m, 1H), 7.63 (t, 1H, J 7.8 Hz), 7.75 (d, 1H, J 8.0 Hz), 7.94 (d, 1H, J 8.0 Hz); C NMR (CDCl 50 MHz): d 29.1,
0.5, 69.5, 70.0, 71.1, 77.2, 113.8, 128.5, 130.9, 132.6, 132.8, 137.5, 140.3, 144.8, 152.1, 169.4; IR (KBr) ν /cm : 3433,
989, 2939, 2889, 1724, 1527, 1350, 1157, 1053; ESI-HRMS (m/z) calc. for C H NO [(M+H) ] 338.1195, found 338.1233.
3
-1
max
+
16
19
7
13
Figure S7. C NMR spectrum of compound 22.

Vol. 22, No. 9, 2011
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S5
1
Figure S8. H NMR spectrum of compound 22.
1
Figure S9. H NMR spectrum of compound 22.

S6
Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
1
Figure S10. H NMR spectrum of compound 22.
Figure S11. IR spectrum of compound 22.

Vol. 22, No. 9, 2011
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S7
Figure S12. ESI-HRMS spectrum of compound 22.
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl(3-nitrophenyl)]methyl) acrylate (23)
1
H NMR (CDCl , 200 MHz): d 1.34 (s, 3H), 1.40 (d, 3H, J 4.0 Hz), 3.65-4.37 (m, 6H), 5.67 (d, 1H, J 4.6 Hz), 6.01 (d,
3
13
1
H, J 5.2 Hz), 6.47 (s, 1H), 7.52 (t, 1H, J 7.8 Hz), 7.75 (d, 1H, J 7.6 Hz), 8.15 (d, 1H, J 8.0 Hz), 8.27 (s, 1H); C NMR
(
CDCl 50 MHz): d 29.1, 30.6, 69.1, 69.9, 75.9, 77.2, 113.8, 125.7, 126.6, 131.4, 133.2, 136.8, 145.1, 147.9, 152.2, 169.4;
3
-1
+
IR (KBr) νmax/cm : 3437, 2989, 2935, 2889, 1716, 1531, 1350, 1157, 1053; ESI-HRMS (m/z) calc. for C H NO [(M+H) ]
16
19
7
3
38.1195, found 338.1239.
13
Figure S13. C NMR spectrum of compound 23.

S8
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J. Braz. Chem. Soc.
1
Figure S14. H NMR spectrum of compound 23.
1
Figure S15. H NMR spectrum of compound 23.

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S9
1
Figure S16. H NMR spectrum of compound 23.
1
Figure S17. H NMR spectrum of compound 23.

S10
Microwave-Promoted Morita-Baylis-Hillman Reactions
J. Braz. Chem. Soc.
Figure S18. ESI-HRMS spectrum of compound 23.
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl(4-nitrophenyl)methyl)] acrylate (24)
1
H NMR (CDCl , 200 MHz): d 1.31 (s, 3H), 1.36 (d, 3H, J 4.0 Hz), 3.62-4.33 (m, 5H), 4.44 (sl, 1H), 5.64 (d, 1H,
3
13
J 4.2 Hz), 5.97 (d, 1H, J 4.8 Hz), 6.41 (s, 1H), 7.55 (d, 2H, J 8.4 Hz), 8.15 (d, 2H, J 8.6 Hz); C NMR (CDCl 50 MHz):
d 29.1, 30.6, 70.0, 69.9, 75.5, 77.2, 113.8, 127.4, 131.2, 131.5, 145.3, 151.2, 153.2, 169.4; IR (KBr) ν /cm : 3410, 3213,
985, 2935, 2897, 1716, 1519, 1350, 1157, 1056; ESI-HRMS (m/z) calc. for C H NO [(M+H) ] 338.1195, found 338.1229.
3
-1
max
+
2
16
19
7
13
Figure S19. C NMR spectrum of compound 24.

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S11
1
Figure S20. H NMR spectrum of compound 24.
1
Figure S21. H NMR spectrum of compound 24.

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J. Braz. Chem. Soc.
1
Figure S22. H NMR spectrum of compound 24.
Figure S23. ESI-HRMS spectrum of compound 24.
(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxy(pyridin-2-yl)methyl)] acrylate (25)
1
H NMR (CDCl , 200 MHz): d 1.30 (s, 3H), 1.36 (d, 3H, J 3.8 Hz), 3.59-4.28 (m, 5H), 4.98 (sl, 1H), 5.59 (s, 1H), 5.97
3
13
(
s, 1H), 6.38 (s, 1H), 7.18 (m, 1H), 7.40 (d, 1H, J 8.0 Hz), 7.65 (td, 1H, J 7.6/1.6 Hz), 8.49 (dd, 1H, J 4.8/1.0 Hz); C NMR
(
(
CDCl 50 MHz): d 29.2, 30.6, 68.7, 70.2, 76.0, 77.2, 113.7, 125.2, 126.6, 131.5, 140.8, 145.4, 152.1, 163.4, 169.8; IR
3
-1
+
KBr) νmax/cm : 3421, 2985, 2939, 2889, 1720, 1157, 1053; ESI-HRMS (m/z) calc. for C H NO [(M+H) ] 294.1296,
15
19
5
found 294.1335.

Vol. 22, No. 9, 2011
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S13
1
Figure S24. H NMR spectrum of compound 25.
1
Figure S25. H NMR spectrum of compound 25.

S14
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J. Braz. Chem. Soc.
1
Figure S26. H NMR spectrum of compound 25.
Figure S27. IR spectrum of compound 25.

Vol. 22, No. 9, 2011
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S15
Figure S28. ESI-HRMS spectrum of compound 25.
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2(hydroxyl(pyridin-3-yl)methyl)] acrylate (26)
1
H NMR (CDCl , 200 MHz): d 1.32 (s, 1H), 1.38 (d, 1H, J 3.2 Hz), 3.58-4.33 (m, 6H), 5.59 (s, 1H), 6.02 (d, 1H, J 3.4 Hz),
3
13
6
.43 (s, 1H), 7.25 (dd, 1H, J 8.0/5.0 Hz), 7.72 (d, 1H, J 8.0 Hz), 8.38 (d, 1H, J 4.6 Hz), 8.47 (d, 1H, J 2.0 Hz); C NMR
(
CDCl 50 MHz): d 29.1, 30.6, 69.9, 70.0, 74.3, 77.2, 113.8, 127.4, 130.7, 141.5, 145.4, 152.3, 152.5, 169.4; IR (KBr)
3
-1
+
νmax/cm :3124, 2989, 2877, 1716, 1145, 1060; ESI-HRMS (m/z) calc. for C H NO [(M+H) ] 294.1296, found 294.1337.
15
19
5
13
Figure S29. C NMR spectrum of compound 26.

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Figure S30. H NMR spectrum of compound 26.
1
Figure S31. H NMR spectrum of compound 26.

Vol. 22, No. 9, 2011
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Figure S32. IR spectrum of compound 26.
Figure S33. ESI-HRMS spectrum of compound 26.

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(
2,2-Dimethyl-1,3-dioxolan-4-yl)methyl[2-(hydroxyl(pyridin-4-yl)methyl)] acrylate (27)
1
H NMR (CDCl , 200 MHz): d 1.34 (s, 3H), 1.39 (d, 3H, J 4.2 Hz), 3.63-4.35 (m, 6H), 5.55 (s, 1H), 5.96 (d, 1H, J 4.6 Hz),
3
13
6
1
.44 (s, 1H), 7.33 (d, 2H, J 6 Hz), 8.46 (d, 2H, J 4.8); C NMR (CDCl 50 MHz): d 29.1, 30.6, 69.0, 69.9, 75.5, 77.2, 113.8,
3
25.5, 131.6, 145.0, 153.4, 155.1, 169.4; IR (KBr) ν /cm : 3140, 2989, 2877, 1716, 1141, 1056; ESI-HRMS (m/z) calc.
for C H NO [(M+H) ] 294.1296, found 294,1337.
-1
max
+
1
5
19
5
13
Figure S34. C NMR spectrum of compound 27.
1
Figure S35. H NMR spectrum of compound 27.

Vol. 22, No. 9, 2011
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S19
1
Figure S36. H NMR spectrum of compound 27.
Figure S37. IR spectrum of compound 27.

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J. Braz. Chem. Soc.
Figure S38. ESI-HRMS spectrum of compound 27.
2
,3-Dihydroxypropyl[2-(hydroxyl(2-nitrophenyl)methyl)] acrylate (8)
1
H NMR (MeOD, 300 MHz): d 3.35 (s, 3H), 3.46-3.55 (m, 2H), 3.79-3.86 (m, 1H), 4.13-4.23 (m, 2H), 5.72-5.74 (m,
13
1
(
1
H), 6.26 (s, 1H), 6.37 (s, 1H), 7.48-7.54 (m, 1H), 7.66-7.72 (m, 1H), 7.77 (d, 1H, J 7.8 Hz), 7.94 (d, 1H, J 8.1 Hz); C NMR
MeOH, 75 MHz): d 64.2, 67.0, 67.6, 71.1, 124.5, 126.4, 129.3, 129.8, 134.3, 138.4, 144.2, 167.1; IR (KBr) νmax/cm :3383,
712, 1527, 1350, 1265, 1157, 1120, 1045; ESI-HRMS (m/z) calc. for C H NO [(M+Na) ] 320.0746, found 320.0748.
-1
+
13
15
7
13
Figure S39. C NMR spectrum of compound 8.