Microwave assisted synthesis of diosgenin esters of maleic and itaconic acids

Article abstract of DOI:10.1080/00397910801997520

Diosgenin monomaleate and diosgenin monoitaconate were prepared by the esterification of diosgenin with maleic and itaconic anhydride, respectively, in toluene using p-toluenesulphonic acid as catalyst. A domestic microwave oven was modified and used for the synthesis of both products. The reaction time for consuming all the diosgenin according to thin-layer chromatography (TLC) was reduced by around 90% in the synthesis of monomaleate of diosgenin as well as in the synthesis of monoitaconate of diosgenin in comparison with conventional heating, whereas the monomaleate of diosgenin yield increased from 43 to 80-85% and the monoitaconate of diosgenin yield from 34 to 95% under the same experimental conditions. It was easier to purify the diosgenin monoitaconate than the diosgenin monomaleate. Both products were characterized by NMR and FTIR spectroscopy. Copyright Taylor & Francis Group, LLC.

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Microwave Assisted Synthesis
of Diosgenin Esters of Maleic
and Itaconic Acids
a
a
Ariel Martínez-García & Ricardo Martínez
a
Laboratorio de Polímeros, IMRE, Universidad de La
Habana , La Habana, Cuba
Published online: 12 Jun 2008.
To cite this article: Ariel Martínez-García & Ricardo Martínez (2008) Microwave
Assisted Synthesis of Diosgenin Esters of Maleic and Itaconic Acids, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:12, 1917-1925, DOI: 10.1080/00397910801997520
To link to this article: http://dx.doi.org/10.1080/00397910801997520
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1
Synthetic Communications , 38: 1917–1925, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910801997520
Microwave Assisted Synthesis of Diosgenin
Esters of Maleic and Itaconic Acids
Ariel Mart ´ı nez-Garc ´ı a and Ricardo Mart ´ı nez
Laboratorio de Pol ´ı meros, IMRE, Universidad de La Habana,
La Habana, Cuba
Abstract: Diosgenin monomaleate and diosgenin monoitaconate were prepared
by the esterification of diosgenin with maleic and itaconic anhydride, respectively,
in toluene using p-toluenesulphonic acid as catalyst. A domestic microwave oven
was modified and used for the synthesis of both products. The reaction time for
consuming all the diosgenin according to thin-layer chromatography (TLC) was
reduced by around 90% in the synthesis of monomaleate of diosgenin as well as
in the synthesis of monoitaconate of diosgenin in comparison with conven-
tional heating, whereas the monomaleate of diosgenin yield increased from 43
to 80–85% and the monoitaconate of diosgenin yield from 34 to 95% under
the same experimental conditions. It was easier to purify the diosgenin monoita-
conate than the diosgenin monomaleate. Both products were characterized by
NMR and FTIR spectroscopy.
Keywords: Diosgenin;
Monomaleate
Modified
microwave
reactor;
Monoitaconate;
INTRODUCTION
Brassinosteroids are polyhydroxylated steroids with high biologic
activity. The synthesis of brassinosteroids analogs has been one of the
more important fields of research since the discovery of these hormones.
[
1,2]
Brosa et al.
have reported the synthesis of colestanics analog deriva-
tives from stigmasterol with different modifications on the steroidal
nucleus and the side chain, and their studies have provided great
Received in the USA January 10, 2008.
Address correspondence to Ricardo Mart ´ı nez, Polymer Laboratory, Institute
of Science and Technology of Materials (IMRE), University of Havana, Havana
1
0400, Cuba. E-mail: ricardo@imre.oc.uh.cu
1
917

1918
A. Mart ´ı nez-Garc ´ı a and R. Mart ´ı nez
relevance to the understanding of the relationship between the chemical
structure of the compounds and their biologic activity. Some designed
Brassinosteroid analogs show drastic modifications but they maintain
their classic function in the A and B rings, keeping at the same time
[
3,4]
high biological activity.
[
Brassinosteroids with biological activity of
[7,8]
5,6]
spirostanic
and furostanic
types are obtained from diosgenin, a
steroidal sapogenin, introducing suitable functional groups in the A
and B rings.
Microwave (MW) technology has been implemented since the middle
of 1980s in the field of organic chemistry. The increasing number of
related publications in recent years indicates that this technique is a
widely accepted unconventional energy source for performing organic
synthesis, and several reviews describe examples of reactions in this
[
9]
[10]
field and also in polymer synthesis.
in chemical reactions is considered a combination of the thermal and
The effect of MW irradiation
[11]
nonthermal effects.
MW-assisted synthesis has been used to prepare several esters, for
instance, propionates,
of interest in the cosmetic field, and 7-ß-hydroxy bile alcohols.
[12]
[13]
[14]
long-chain aliphatic
and aromatic
esters
[
15]
Some authors have concluded, based on kinetics studies, that the rate
of the esterification remains the same both under MW and conventional
[
16,17]
heating.
irradiation has been reported by other authors.
ification are striking. For instance, the polycondensation of succinic acid
However, the acceleration of the esterification by MW
[
15,18]
Results in polyester-
[
19]
and butanediol undergoes 10-fold acceleration under MW irradiation
and lactic acid produces polymers with molecular weights of 16,000 h
whereas the conventional heating system gave no polymer under the same
[
20]
conditions.
Although MWs have been applied to steroid synthetic pro-
[
21,22]
cedures,
no report about the MW-assisted synthesis of brassinoster-
oids or diosgenin derivates has been published. We report herein a
facile high-yielding synthesis of diosgenin monomaleate and diosgenin
monoitaconate in a short time using a modified commercial domestic
MW oven.
RESULTS AND DISCUSSION
The focus of this work was the development of a simple method to pre-
pare two vinyl monomers from diosgenin [5(22a)-spirosten-3b-ol], which
could be copolymerized by radical initiation to produce amphiphilic
copolymers. The monomaleate of diosgenin (1) and monoitaconate of
diosgenin (2) fulfill these features.

Diosgenin Esters of Maleic and Itaconic Acids
1919
The syntheses of monomers 1 and 2 were carried out by the esterifi-
cation of diosgenin with the corresponding anhydrides, maleic and itaco-
nic, heating the solution of the reactants to reflux in pyridine or toluene.
The yields using these solvents were similar (see Table 1) but the synthesis
process conducted in toluene requires fewer steps. As a result, toluene
was selected as solvent to prepare the monomers by MW irradiation.
A domestic MW oven was modified in a way similar to those
[23,24]
described in previous articles
and was used to synthesize 1 and 2.
A circular hole was bored in the ceiling, which allows a pyrex tube to
be fixed with joints at both ends. A round-bottomed flask was attached
to the inner one and a reflux condenser with Dean–Stark trap to the
1
external end of the tube. The use of the turntable dish with a Teflon ring
between it and the round-bottomed flask avoids the excessive tempera-
ture increase in those points in which the radiation is higher inside
the oven.
Table 1. Results of the synthesis of diosgenin esters of maleic and itaconic acids
(
MMD and MID respectively) by different methods
Reaction
method
D t
Solvent tr (min) (%)
r
Temp. Yield
ꢀ
a
Synthesis
MMD
( C)
(%)
b
Microwave irradiation Toluene
15
15
110
110
80–85
43
60
55–60
95
34
b
Oil bath
Oil bath
Oil bath
Toluene
b
Toluene 160–180 91–92 110
Pyridine 150–180 90–92
c
115
b
b
b
MID
Microwave irradiation Toluene
Toluene
10
10
110
110
Oil bath
Oil bath
Toluene 120–140 92–93 110
80
a
Dt (%) ¼ (t conv. heat. ꢁ t MW irradiation) ꢂ 100=t conv. heat.
r
r
r
r
b
Boiling point of toluene.
Boiling point of pyridine.
c
r
Note. The reaction time (t ) corresponds to the diosgenin exhaust according
to TLC.

1920
A. Mart ´ı nez-Garc ´ı a and R. Mart ´ı nez
Table 1 compares the results of the synthesis by MW irradiation with
those obtained by conventional heating. The comparison criteria were the
reaction time for consuming all the diosgenin according to thin-layer
chromatography (TLC) and the yields obtained by both methods for
the same reaction time. The first criterion indicates a reduction in reac-
tion times by MW irradiation by about 90% for monomaleate of dios-
genin as well as for monoitaconate of diosgenin when compared to
heating in the oil bath. The second criterion show that the yield increases
from 43 to 80–85% for 1 and from 34 to 95% for 2.
The yields of 2 were always greater, and its purification was easier
than the corresponding yields of 1. Both products were characterized
by NMR and FTIR.
CONCLUSIONS
Diosgenin esters of maleic and itaconic acids can be prepared by
MW-assisted synthesis in less time and with higher yield than using
conventional heating. The monoitaconate of diosgenin can be obtained
with greater yield than monomaleate of diosgenin.
EXPERIMENTAL
Materials
Maleic anhydride PS (Merck), itaconic acid PS (SIGMA), acetyl chloride
PS (Panreac), toluene-4-sulphonic acid PS (BDH), benzene PS (Merck),
toluene PA (BDH), and commercial diosgenin were used without further
purification. Ethanol (95%) and chloroform were distilled previously.
Synthesis of Monomaleate of Diosgenin by Conventional Heating
Using Pyridine as Solvent
ꢁ
2
A mixture of maleic anhydride (0.98 g, 1 ꢂ 10 mol), diosgenin (0.745 g,
ꢁ
3
1
.8 ꢂ 10 mol), and 5 mL of pyridine in a round-bottomed flask was
heated to reflux with an oil bath. The completion of the reaction was con-
firmed by TLC by the examination of samples every 20 min. The mixture,
under stirring, was poured into a cold 0.1% HCl aqueous solution. Ice
was added to keep the mixture cold for 2–3 h. The resulting product
was separated by filtration, washed with water, and dried under vacuum
(P ¼ 9 mbar) at room temperature.

Diosgenin Esters of Maleic and Itaconic Acids
1921
Using Toluene as Solvent
ꢁ
2
A mixture of maleic anhydride (2.45 g, 2.5 ꢂ 10 mol), diosgenin (1.86 g,
ꢁ
2
0
3
.45 ꢂ 10 mol), toluene-4-sulphonic acid (12 mg, 0.25% in weight), and
0 mL of toluene in a round-bottomed flask was heated to reflux with
an oil bath. The completion of the reaction was confirmed by TLC by
the examination of samples every 20 min. A synthesis was also carried
out under the same conditions but with a reaction time of 15 min. In both
ꢀ
cases, the solvent was removed using a rotary evaporator (T ¼ 45 C;
P ¼ 75 mbar). The resulting residual solid was washed three times with
5
0 ml of water and dried under vacuum at room temperature.
Purification
The solid resulting from these two procedures, after the reaction was
completed, was dissolved in 30 mL of hot ethanol. Two fractions of the
product were collected by filtration after cooling the solution first to
ꢀ
room temperature and later to 2–3 C. Both fractions were dried under
vacuum (P ¼ 9 mbar), and a bone-white fine powder was obtained (yield:
A ¼ 55–60% and B ¼ 60%).
When the reaction time was 15 min, diosgenin was not consumed
totally. In this case, the solid obtained, after washing and drying, was
purified by column chromatography (yield: 43%) because the previously
purification procedure cannot be used to separate the mixture of the ester
and diosgenin.
Synthesis of Monomaleate of Diosgenin by Microwave Irradiation
A mixture of maleic anhydride (9.8 g, 0.1 mol), diosgenin (7.45 g,
ꢁ
2
1
1
.8 ꢂ 10 mol), toluene-4-sulphonic acid (45 mg, 0.25% in weight), and
20 mL of toluene in a round-bottomed flask was subject to MW
irradiation at 1000 W. The completion of the reaction was confirmed
by TLC by the examination of samples every 5 min. The solvent was
ꢀ
removed in a rotary evaporator (T ¼ 45 C; P ¼ 75 mbar), and the
residual solid was washed three times with 50 mL of water and dried
under vacuum at room temperature. The solid was purified as described
ꢀ
previously (yield 85%). Melting point: 203.6 C. Elemental analysis: C,
7
2.73% (calc. 72.63%); H, 8.50% (calc. 8.65%); O, 18.77 (calc. 18.72%).
The FTIR spectrum presents the bands corresponding to tOH,
ꢁ
1
a wide band with center at 3033 cm
ꢁ
and shoulders at 2690,
ꢁ1
1
ꢁ1
2
570 cm ; tCsp -H at 2946, 2902, 2871 cm ; tC=O at 1725 cm
tC=C at 1635 cm ; tCꢁCOꢁO at 1240, 1211, 1165 cm , and
;
3
ꢁ
1
ꢁ1
tOꢁCꢁC at 1051 cmꢁ
1
.

1922
A. Mart ´ı nez-Garc ´ı a and R. Mart ´ı nez
1
The H NMR spectrum shows doublets at 6.29 ppm (1H-29,
J ¼ 12.5 Hz) and at 6.39 ppm (1H-30, J ¼ 12.7 Hz) assigned to vinyl pro-
tons arising from maleic anhydride. The rest of the signals correspond to
the diosgenin moiety: 0.76 (d, 3H-27, J ¼ 5.8 Hz); 0.77 (s, 3H-18); 0.95 (d,
3
1
5
7
H-21, J ¼ 6.8 Hz); 1.02 (s, 3H-19); 3.35 (t, 1H-26ax, J ¼ 10.7); 3.46 (dd,
H-26ec, J ¼ 10.2=3.2 Hz); 4.39 (m, 1H-16a ); 4.73 (m wide, 1H-3a);
1
3
.39 (d, 1H-6, J ¼ 4.2 Hz). C NMR (d, ppm): C 36.82; C 27.41; C
1
2
3
6.80; C 37.66; C 138.94; C 123.17; C 32.05; C 31.39; C 49.82;
4
5
6
7
8
9
C10 36.72; C11 20.84; C12 39.70; C13 40.27; C14 56.43; C15 31.82; C16
0.82; C17 62.07; C18 16.28; C19 19.29; C20 41.65; C21 14.51; C22 109.37;
C23 31.39; C24 28.79; C25 30.28; C26 66.85; C27 17.14; C28 166.77; C29
29.70; C30 135.19; C31 165.64.
8
1
Synthesis of Itaconic Anhydride
A mixture of 35 g of itaconic acid and 70 mL of acetyl chloride was
refluxed on the steam bath for 2 h and 30 min. The solution was evapo-
ꢀ
rated by rotary evaporation to dryness in vacuum (bath 70–80 C). The
evaporation was repeated with two portions of 40 mL of toluene, and
then the residual anhydride solidified on cooling. The anhydride was
recrystallized from benzene followed by cooling to give a crystalline solid,
ꢀ
yield 75% and mp 68.5–69.5 C.
Synthesis of Monoitaconate of Diosgenin by Conventional Heating
ꢁ
2
A mixture of itaconic anhydride (0.672 g, 0.6 ꢂ 10 mol), diosgenin
ꢁ
2
(
2.07 g, 0.5 ꢂ 10 mol), p-toluensulphonic acid (8 mg, 0.25% in weight),
and 25 mL of toluene in a two-neckes round flask was heated to reflux
with an oil bath. The completion of the reaction was confirmed by
TLC by the examination of samples every 20 min. A synthesis was also
carried out with a reaction time of 10 min. In both cases, the solvent
ꢀ
was removed in a rotary evaporator (T ¼ 45 C ; P ¼ 75 mbar), and the
residual solid was washed three times with 50 mL of water and dried
under vacuum at room temperature.
Purification
ꢀ
The solid was dissolved in 30 mL of ethanol at 70 C. The solution was
hot filtered and added to 250 mL of water to obtain a precipitate. The
product was washed twice with 30 mL of water, filtered, and dried under
vacuum. A fine power of bone-white color was obtained. Synthetic
yield: 80%.

Diosgenin Esters of Maleic and Itaconic Acids
1923
When the reaction time was 10 min, the solid obtained after wash-
ing and drying was purified by column chromatography (yield: 34%)
because the previously mentioned purification procedure cannot be used
to separate the mixture of the ester and diosgenin.
Synthesis of Monoitaconate of Diosgenin by Microwave Irradiation
ꢁ
2
A mixture of itaconic anhydride (1.344 g, 1.2 ꢂ 10 mol), diosgenin
ꢁ
2
(
4.14 g, 1 ꢂ 10 mol), p-toluensulphonic acid (20 mg, 0.25% in weight),
and 50 mL of toluene in a two-necked round-bottomed flask was submit-
ted to the procedure describe previously for the monomaleate of dios-
genin synthesis. The reaction was finished in 10 min, and the toluene
ꢀ
was removed by rotary evaporation (T ¼ 45 C; P ¼ 75 mbar). The solid
was dried under vacuum at room temperature and dissolved in 30 mL of
ethanol at 70 C. The solution was hot filtered and added to 250 mL of
water to obtain a precipitate. The product was washed twice with
ꢀ
3
temperature. A fine power of bone-white color was obtained (yield
0 mL of water, filtered, and dried under vacuum (P ¼ 9 mbar) at room
ꢀ ꢀ
5%). Melting point: 213.8 C, decomposition 243 C. Elemental analysis:
9
C 73.01% (calc. 72.97%); H 8.66% (calc. 8.80%); O 18.33 (calc. 18.23%).
The FTIR spectrum presents the bands corresponding to tOH, a
wide band with center at 3000 cm ; and a shoulder at 2620 cm ;
ꢁ
1
ꢁ1
ꢁ
1
ꢁ1
tCsp -H at 2948, 2906, 2870 cm ; tC=O (ester) at 1735 cm ; tC=O
3
ꢁ
1
ꢁ1
ꢁ1
(
acid) at 1701 cm ; tC=C at 1636 cm ; tCꢁCOꢁO at 1164 cm
,
ꢁ
1
1
and tOꢁCꢁC at 1051 cm . The H NMR spectrum shows three signals
corresponding to the monoitaconate contribution: a singlet at 3.30 ppm
(
2H-29) assigned to the ꢁCH aliphatic protons and two singlets at
2
5
.79 ppm (1H-31a) and 6.42 (1H-31b) assigned to the vinyl protons.
The rest of the signals correspond to the diosgenine moiety: 0.76 (d,
H-27, J ¼ 5.6 Hz); 0.77 (s, 3H-18); 0.95 (d, 3H-21, J ¼ 6.6 Hz); 1.01
s, 3H-19); 3.30 (s, 2H-29); 3.35 (t, 1H-26ax, J ¼ 10.7); 3.44 (dd, 1H-
6ec, J ¼ 10.17=2.8 Hz); 4.39 (m, 1H-16a); 4.61 (m, wide, 1H-3a); 5.34
3
(
2
(
1
3
d, 1H-6, J ¼ 3.5 Hz). C NMR (d, ppm): C 36.90; C 27.57; C 74.59;
4 5 6 7 8 9 10
1
2
3
C 37.68; C 139.54; C 122.42; C 32.02; C 31.34; C 49.91; C 36.69;
C11 20.80; C12 39.71; C13 40.24; C14 56.41; C15 31.78; C16 80.82; C17
2.01; C18 16.25; C19 19.31; C20 41.60; C21 14.48; C22 109.35; C23 31.37;
C24 28.75; C25 30.25; C26 66.82; C27 17.10; C28 169.94; C29 37.89; C30
33.46; C31 130.33; C32 170.98.
6
1
Apparatus
MW irradiation was carried out using a domestic MW oven LG MB-
3
14XF. Elemental analysis for C and H were performed on Leco, model

1924
A. Mart ´ı nez-Garc ´ı a and R. Mart ´ı nez
CHNS-932. Melting points were determined using Mettler Toledo DSC
ꢀ
equipment at a heating rate of 10 C=min. Attenuated total reflection
Fourier transform infrared (ATR-FTIR) spectra were recorded with a
Perkin-Elmer 2000 FTIR spectrometer equipped with ATR accessory
from Specac. The spectrometer was equipped with a nitrogen-cooled
1
13
MCT detector. H and CNMR spectra were recorded with a Bruker
AC 250 F spectrometer equipped with a computer Aspect 3000, operating
1
13
at 250 MHz for H and 62.89 MHz for C. All samples were dissolved in
chloroform (d).
REFERENCES
1
2
3
. Brosa, C.; Mir oꢀ , X. Synthesis of new brassinosteroids with epoxy functions:
The effect on the regioselectivity of the Baeyer-Villiger reaction. Tetrahedron
1997, 53, 11347–11354.
. Brosa, C.; Soca, L.; Terricabras, E.; Ferrer, J. C.; Alsina, A. New synthetic
brassinosteroids: A 5a-hydroxy-6-ketone analog with strong plant growth
promoting activity. Tetrahedron 1998, 54, 12337–12348.
. Kohout, L.; Kasal, A.; Strnad, M. Pregnane-type brassinosteroids with a
four-carbon ester functionality in position 20. Collect. Czech. Chem. Com-
mun. 1996, 61, 930–940.
4. Kohout, L.; Slavikoba, B.; Strand, M. 17a-Oxa-17a-homobrassinosteroid
analogues. Collect. Czech. Chem. Commun. 1998, 63, 646–654.
5
. Iglesias-Arteaga, M. A.; P e´ rez Gil, R.; P e´ rez Mart ´ı nez, C. S.; Coll Manchado,
F. Spirostanic analogues of teasterone: Synthesis, characterization, and bio-
logical activity of laxogenin, (23S)-hydroxylaxogenin and 23-ketolaxogenin
(
23-oxolaxogenin). J. Chem. Soc., Perkin Trans. 2001, 3, 261–266.
6
7
8
9
. Iglesias-Arteaga, M. A.; P e´ rez Gil, R.; Leliebre Lara, V.; P e´ rez Mart ´ı nez, C.
S.; Coll Manchado, F. Synthesis of (25 R)-2a,3a-epoxy-5a-spirostan-6,23-
dione. Synth Commun. 1998, 28, 4387–4392.
. Iglesias-Arteaga, M. A.; P e´ rez Gil, R.; Leliebre Lara, V.; P e´ rez Mart ´ı nez, C.
S.; Coll Manchado, F. Synthesis of (25 R)-2a,3a,26-trihydroxy-5a-furostan-6-
one. Synth Commun. 1998, 28, 1779–1784.
. Iglesias-Arteaga, M. A.; P e´ rez Gil, R.; Leliebre Lara, V.; P e´ rez Mart ´ı nez, C.
S.; Rosado, A.; Coll Manchado, F. Synthesis of (25 R)-3b,26-dihydroxy-5a-
furostan-6-one. Synth Commun. 1998, 28, 1381–1386.
. (a) Loupy, A. (Ed.). Microwaves in Organic Synthesis; Wiley-VCH: Wein-
heim, 2006; (b) Kappe, C. O.; Stadler, A. Microwaves in Organic and Med-
icinal Chemistry; Wiley-VCH: Weinhiem, 2005; (c) Lidstr o¨ m, P.; Tierney, J.
P. (Eds.). Microwave-Assisted Organic Synthesis; Blackwell: Oxford, 2005;
(
d) Hayes, B. L. Microwave Synthesis: Chemistry at the Speed of Light;
CEM Publishing: Matthews, NC, 2002; (e) Lidstr o¨ m, P.; Tierney, J.;
Wathey, B.; Westman, J. Microwave assisted organic synthesis—A review.
Tetrahedron 2001, 57, 9225–9283.

Diosgenin Esters of Maleic and Itaconic Acids
1925
1
0. Hoogenboom, R.; Schubert, U. S. Microwave-assisted polymer synthesis:
Recent developments in a rapidly expanding field of research. Macromol.
Rapid Commun. 2007, 28, 368–386.
1
1. (a) de la Hoz, A.; D ´ı az-Ortiz, A.; Moreno, A. Microwaves in organic syn-
thesis: Thermal and non-thermal microwave effects. Chem. Soc. Rev. 2005,
34, 164–178; (b) Kappe, C. O. Controlled microwave heating in modern
organic synthesis. Angew. Chem. Int. Ed. 2004, 43, 6250–6284.
1
1
1
1
1
1
1
1
2
2
2. Amore, K. M.; Leadbeater, N. E. Microwave-promoted esterification reac-
tions: Optimization and scale-up. Macromol. Rapid Commun. 2007, 28,
473–477.
3. Villa, C.; Mariani, E.; Loupy, A.;Grippo, C.; Grossi, G. C.; Bargagna, A.
Solvent-free reactions as green chemistry procedures for the synthesis of
cosmetic fatty esters. Green Chem. 2003, 5, 623–626.
4. Villa, C.; Baldassari, S.; Gambaro, R.; Mariani, E.; Loupy, A. Eco-friendly
methodologies for the synthesis of some aromatic esters, well-known
cosmetic ingredients. Internat. J. Cosmetic Sci. 2005, 27, 11–16.
5. Dayal, B.; Ertel, N. H.; Padia, J.; Rapole, K. R.; Salen, G. 7b-Hydroxy bile
1
alcohols: Facile synthesis and 2D H NMR studies of 5b-cholestane-3a,
7b,12a ,25-tetrol. Steroids 1997, 62, 409–414.
6. Pollington, S. D.; Bond, G.; Moyes, R. B.; Whan, D. A.; Candlin, J. P.;
Jennings, J. R. The influences of microwave on the rate of reaction of
propan-1-ol with ethanoic acid. J. Org. Chem. 1991, 56, 1313–1314.
7. Raner, K. D.; Strauss, C. R. Influence of microwaves on the rate of esterifi-
cation of 2,4,6-trimet hylbenzoic acid with 2-propanol. J. Org. Chem. 1992,
57, 6231–6234.
8. Roy, I.; Gupta, M. N. Non-thermal effects of microwaves on protease-
catalyzed esterification and transesterification. Tetrahedron 2003, 59,
5431–5436.
9. Velmathi, S.; Nagahata, R.; Sugiyama, J. I.; Takeuchi, K. A rapid eco-
friendly synthesis of poly(butylene succinate) by a direct polyesterification
under microwave irradiation. Macromol. Rapid Commun. 2005, 26, 1163.
0. Nagahata, R.; Sano, D.; Suzuki, H.; Takeuchi, K. Microwave-assisted single-
step synthesis of poly(lactic acid) by direct polycondensation of lactic acid.
Macromol. Rapid Commun. 2007, 28, 437–442.
1. Kahn, M. G. C.; Konde, E.; Dossou, F.; Labaree, D. C.; Hochberg, R. B.;
Hoyte, R. M. Microwave-enhanced nucleophilic fluorination in the synthesis
of fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids, potential glu-
cocorticoid receptor-mediated imaging agents. Bioorg. Med. Chem. Lett.
2006, 16, 3454–3458.
2
2. Tietze, L. F.; Wiegand, J. M.; Vock, C. Synthesis of enantiopure B-
nor-steroids by multiple Pd-catalyzed transformations. J. Org. Chem. 2003,
687, 346–352.
2
3. Narasimhan, S.; Velmathi, S. Effect of microwaves in the chiral switching
asymmetric Michael reaction. Molecules 2003, 8, 256–262.
2
4. Zhang, G.; Niu, A.; Peng, S; Jiang, M.; Tu, Y.; Li, M.; Wu, C. Formation of
novel polymeric nanoparticles. Acc. Chem. Res.. 2001, 34, 249–256.