Solvent-Free Microwave-Assisted Efficient Synthesis of 4,4-Disubstituted 2-Oxazolines

Article abstract of DOI:10.1002/ejoc.200200469

4,4-Disubstituted 2-oxazolines have been synthesized by a microwave-promoted solvent-free direct condensation of carboxylic acids and disubstituted β-amino alcohols in good to excellent yields. Zinc oxide is a very good solid support in cases where a Lewis acid is required. The method described herein is a very good, safe, clean, economical, and environmentally friendly alternative to the classical procedures. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200200469

FULL PAPER
Solvent-Free Microwave-Assisted Efficient Synthesis of 4,4-Disubstituted
2-Oxazolines
[a]
[b]
[b]
´
´
Fernando Garcıa-Tellado, Andre Loupy, Alain Petit, and
Alma Leilani Marrero-Terrero*[c]
Keywords: Microwaves / Zinc / Nitrogen heterocycles / Carboxylic acids / Amino alcohols
4,4-Disubstituted 2-oxazolines have been synthesized by a
microwave-promoted solvent-free direct condensation of
carboxylic acids and disubstituted β-amino alcohols in good
to excellent yields. Zinc oxide is a very good solid support in
cases where a Lewis acid is required. The method described
herein is a very good, safe, clean, economical, and environ-
mentally friendly alternative to the classical procedures.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
when this new technique has been coupled with solvent-free
procedures, resulting in clean, easy-to-perform, cheap, safe
and environmentally friendly conditions which are widely
used as synthetic tools[8Ϫ10] under ‘‘Green Chemistry’’ con-
ditions.[11] Furthermore, the development of monomode re-
actors, taking advantage of wave focussing and accurate
control of temperature by infrared detection[12] (and its
monitoring according to emitted MW power), has en-
hanced this technique mainly due to better reproducibility
and predictability of results and, in turns better control and
optimization of the procedures.
2-Oxazolines constitute a wide family of five-membered
heterocycles with important applications in the fields of or-
ganic synthesis[1] and pharmacology.[2,3] These heterocycles
are readily prepared from N-acyl derivatives of β-hy-
droxylamines by heating or by the action of a dehydrating
agent such as thionyl chloride, sulfuric acid, or phosphor-
ous pentoxide.[4] The direct condensation of carboxylic ac-
ids with β-hydroxylamines requires high temperatures and
strongly acidic conditions,[3] and is therefore not a syntheti-
cally valuable method to access these heterocycles. Alterna-
tive procedures using imino ether hydrochlorides, nitriles
and isocyanides have been described.[4] Vorbrüggen et al.[3]
have developed a one-pot protocol for the transformation
of carboxylic acids into 2-oxazolines using Ph3P/CCl4 as a
chemical activator. Natale et al.[5] have shown that car-
boxylate esters can be directly transformed into 2-oxazol-
ines using lanthanide chloride as catalyst.
We have shown in a preliminary communication[13] that
some 4,4-bis(hydroxymethyl)-2-oxazolines are easily ob-
tained from the direct, solvent-free microwave-assisted con-
densation of carboxylic acids 1 with the β-amino alcohol
2a (Table 1). In this paper we report the extension of this
procedure to the synthesis of a wide set of 4,4-disubstituted
2-oxazolines 3aϪi (Table 1). While the microwave-assisted
solvent-free direct condensation of the carboxylic acids
1aϪi with the β-amino alcohols 2a and 2b afforded
2-oxazolines 3(a؊f)(a؊b) in very good yields (Table 2), the
reactions with 2c called for a Lewis acidic solid support
(Table 3).
Organic synthesis assisted by microwave (MW) has seen
spectacular growth over the last few years.[6,7] Particularly
[a]
´
Instituto de Productos Naturales y Agrobiologıa (CSIC),
´
´
Astrofısico Francisco Sanchez 3, 38206 La Laguna, Tenerife,
Spain
Fax: (internat.) ϩ34-922260135
E-mail: fgarcia@ipna.csic.es
Results and Discussion
[b]
[c]
´
´
Laboratoire des Reactions Selectives Sur Supports (CNRS),
´
UMR 8615, Universite Paris Sud,
Perreux and Loupy[14] have rationalized the still contro-
versial specific microwave effect[14,15] in organic synthesis on
the basis of medium effects and mechanistic considerations.
They postulate that a bimolecular reaction between neutral
reactants should be assisted by microwave irradiation as the
reaction goes through a dipolar transition state (TS). This
dipolar transition state (TS) is prone to develop more ef-
ˆ
Batiment 410, 91405 Orsay Cedex, France
Fax: (internat.) ϩ33-169154679
E-mail: aloupy@icmo.u-psud.fr
´
Centro Nacional de Investigaciones Cientıficas (CNIC),
´
´
Direccion de Diagnostico (DIRAMIC),
´
Avenida 25 N° 15202 esq. 158, Cubanacan, Playa, Apartado
6414, Ciudad de La Habana, Cuba
Fax: (internat.) ϩ537-2087358
E-mail: leilani@diramic.cneuro.edu.cu
Eur. J. Org. Chem. 2003, 4387Ϫ4391
DOI: 10.1002/ejoc.200200469
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4387

´
F. Garcıa-Tellado, A. Loupy, A. Petit, A. L. Marrero-Terrero
FULL PAPER
Table 1. 2-Oxazolines synthesized in this work
Carboxylic acid
Amino alcohol
2-Oxazoline
R
R1
R2
1a
1a
1a
1b
1b
1c
1c
1c
1d
1e
1f
2a
2b
2c
2a
2c
2a
2a
2b
2a
2a
2a
2c
2c
2c
3aa
3ab
3ac
3ba
3bc
3ca
3cabis
3cb
3da
3ea
3fa
C6H5
C6H5
C6H5
C4H3O
C4H3O
C17H35
C17H35
C17H35
o-Cl-C6H4
m-Cl-C6H4
p-Cl-C6H4
p-OCH3ϪC6H4
p-NO2ϪC6H4
C15H31
CH2OH
CH2OCOC6H5
CH3
CH2OH
CH3
CH2OH
CH2OCOC17H35
CH3
CH2OH
CH2OH
CH2OH
CH3
CH2OH
CH3
CH3
CH2OH
CH3
CH2OH
CH2OCOC17H35
CH2OCOC17H35
CH2OH
CH2OH
CH2OH
CH3
1g
1h
1i
3gc
3hc
3ic
CH3
CH3
CH3
CH3
ficient stabilizing electrostatic interactions with the applied yields.[16Ϫ20] In the case of β-amino alcohols, once the am-
electromagnetic field (of a dipole-dipole nature) than the ides are formed, subsequent intramolecular condensation
neutral ground state (GS) due to dipole apparition during between the amides and the free hydroxyl groups present in
the course of the reaction. This results in a decrease in the the molecule can afford 2-oxazolines (Table 1).
energy of activation. As a corollary, as the TS is displaced
further along the reaction coordinates (more product-like
Because of the polar nature of the transition states in-
TS) the more prone it will be to develop an increased po- volved in these processes, the microwave irradiation should
larity and the more pronounced will be the microwave ef- help to drive the reaction to completion. Furthermore, the
fect.
final temperature reached (T Ͼ 150 °C) implies that the
The condensation reaction between amines and car- formed water is removed from the reaction medium render-
boxylic acids leading to amides fulfils the above require- ing the global process irreversible, irrespective of the mode
ments. As expected, the microwave-assisted solvent-free di- of activation (MW irradiation or conventional heating).
rect preparation of amides from carboxylic acids and am- With this idea in mind, we have irradiated several solid mix-
ines has been described to proceed smoothly and in good tures of carboxylic acids 1aϪi and β-amino alcohols 2aϪc
Table 2. Solvent-free microwave-assisted synthesis of 2-oxazolines 3(a-f)(a-b) by reacting equivalent amounts (10 mmol) of 1 and 2
Entry
Microwave equipment
Power (W)
Time (min)
Final temp. (°C)
Product
Yield (%)
1
2
3
Multimode
Monomode
Multimode
Monomode
Multimode
Multimode
Monomode
Multimode
Monomode
Multimode
Monomode
Multimode
Monomode
Multimode
Multimode
Monomode
850
90
850
90
3.25
6
3
4
10
6
13
3.5
5
3.4
3
5.5
5
13
3.5
5
206
223
200
197
220
204
214
210
200
228
202
230
200
210
198
219
3aa
88
84
81
84
95
97
97
52
80
55
80
60
95
97
94
96
3aa
3ba
3ba
850
850
300
850
150
850
150
850
300
850
850
150
3ca
3cabis[a]
3ca
4
5
6
3da
3da
3ea
3ea
3fa
3fa
7
8
3cb[b]
3ab[b]
3ab[b]
[a]
[b]
3 equiv. of carboxylic acid was used. 2 equiv. of carboxylic acid was used.
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 4387Ϫ4391

Solvent-Free Microwave-Assisted Efficient Synthesis of 4,4-Disubstituted 2-Oxazolines
FULL PAPER
to obtain the five-membered heterocycles according to a
one-step procedure.
While the irradiation of the mixtures containing 2a or 2b
afforded 2-oxazolines in excellent yields irrespective of the
Tables 2 and 3 summarizes the yields obtained and exper- carboxylic acid used (Table 2), those involving 2c failed to
imental conditions under MW irradiation using two kinds give the expected heterocycles.[27] In these cases, the process
of equipment, either a domestic oven (multimode) or a requires a solid acid support to go to completion. For this
monomode reactor with focused waves (Prolabo S402 and purpose, zinc oxide was found to be the most efficient. It
Maxidigest MX350 systems).
acts both as a solid support and as a soft Lewis acid cata-
From Table 2 it is obvious, as found in a lot of cases[21Ϫ26] lyst. Other acidic solid supports (montmorillonites KSF
that the monomode reactor leads to better yields than the and K10, calcinated Al2O3, SiO2) were unsuccessful
multimode oven and requires a lower irradiation power le- (Table 3).
vel (entries 4, 5, and 6). The electronic nature of the R
The zinc oxide seems to play a double role: it creates a
group does not seem to be a limiting factor and both ali- polar environment for the microwave catalysis[28] (polar
phatic and aromatic carboxylic acids can be used with the solid support) and activates the carbonyl group for the con-
same efficiency (entries 1, 2, 3, and 8). When more than one densation (Lewis acid catalyst). The results summarized in
equivalent of the carboxylic acid is used, further esterifi- Table 3 show that the monomode is here again more effec-
cation of the free hydroxyl groups on the heterocycles takes tive than the multimode (entry 1) and that the method is
place to give the mono- or di-ester derivatives (entries 3, 7, quite general and insensitive to the electronic nature of the
and 8). The presence of at least two hydroxyl groups in the carboxylic acid used (entries 3, 4, and 5).
amino alcohol seems to be crucial to promote the further
The existence of specific microwave effects[6] was evident
condensation. In the absence of such a second hydroxyl since the same reactions using a thermostatted oil-bath un-
group, the condensation needs a catalyst to proceed and we der identical conditions as for the microwave-assisted reac-
found that zinc oxide was a very convenient additive. We tions gave only traces of the heterocycles.
believe that the key role of the second hydroxyl group is to
form an internal H-bond with the carbonyl group of the
amide to provide some electrophilic assistance for the next
condensation. This mechanism is also highly propitious for
Conclusion
MW specific effects as it involves a dipolar TS from neutral
reactants (Figure 1).
In summary, we have shown that the synthesis of 4,4-
disubstituted 2-oxazolines by direct condensation of a car-
boxylic acid and a substituted β-amino alcohol is feasible
using microwave technology under solvent-free conditions.
Zinc oxide can be used as a solid support in those cases in
which a Lewis acid is required. The process is safe, clean,
economical, and environmentally friendly.
Experimental Section
General Remarks: Melting points are uncorrected and were deter-
mined in a Reichter Thermovar apparatus. 1H NMR and 13C NMR
spectra of CDCl3 or [D6]DMSO solutions were recorded either at
250 MHz or 200 and 50 MHz or at 500 and 125 MHz (Bruker Ac
200 and AMX2Ϫ500), respectively. FT-IR spectra were registered
as KBr discs or chloroform solutions using a Shimadzu IR-408
spectrophotometer. Mass spectra (low resolution) (EI/CI) were ob-
tained with a HewlettϪPackard 5995 gas chromatograph/mass
spectrometer. High-resolution mass spectra were recorded with a
Micromass Autospec mass spectrometer. Microanalyses were per-
Figure 1. Mechanism of the synthesis of 2-oxazolines from a car-
boxylic acid and a β-amino alcohol
Table 3. Synthesis of 4,4-dimethyl 2-oxazolines 3(a-i)c by reacting 1 and 2c impregnated on zinc oxide under MW solvent-free conditions
Entry
1
Microwave equipment
Power (W)
Time (min)
Final temp. (°C)
Product
Yield (%)
Multimode
Monomode
Monomode
Monomode
Monomode
Monomode
850
60
150
60
60
60
0.25
3
0.5
9
4
5
205
185
203
208
220
220
3ac
3ac
3bc
3gc
3hc
3ic
78
90
83
91
76
84
2
3
4
5
Eur. J. Org. Chem. 2003, 4387Ϫ4391
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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´
F. Garcıa-Tellado, A. Loupy, A. Petit, A. L. Marrero-Terrero
FULL PAPER
formed with a Fisons Instruments EA 1108 carbon, hydrogen, and
pyl alcohol). IR (KBr, cmϪ1): ν˜ ϭ 1727 (CϭO), 1649 (CϭN). H
1
nitrogen analyser. Analytical thin-layer chromatography plates used NMR (250 MHz, CDCl3, ppm): δ ϭ 1.5 (s, 3 H, Me), 4.38 (s, 2 H,
were E. Merck Brinkman Uvactive silica gel (Kieselgel 60 F254) 2 ϫ 5-H), 4.5 (d, J ϭ 9 Hz, 2 H, CH2OCO), 7.4 (m, 6 H, Ar-H),
on aluminium. Reactions were performed in a domestic microwave 8.0 (m, 4 H, Ar-H). HRMS (CI) (NH3): m/zϭ 296 [M ϩ 1].
oven Goldstar Model MA 1197M (850 watt), a Maxidigest MX350
modified monomode reactor or a S402 from Prolabo. Compound
(2-Heptadecyl-4-methyl-4,5-dihydro-1,3-oxazol-4-yl)methyl Octade-
canoate (3cb): Mol. mass 620.06; 97% yield (6.01 g); m.p. 67Ϫ68
names were obtained using the ACD/I-Lab Web service (ACD/IU-
°C (CHCl3/MeOH, 1:1). IR (KBr, cmϪ1): ν˜ ϭ 1732 (CϭO), 1662
PAC Name Free 6.00). Oxazolines 3aa, 3ba, and 3ca have been fully
1
(CϭN). H NMR (250 MHz, CDCl3, ppm): δ ϭ 0.9 (t, J ϭ 7 Hz,
described in our preliminary communication.[13] Oxazoline 3ac is
6 H, 3 ϫ Me), 1.26 (m, 56 H, 28 ϫ CH2), 1.30 (s, 3 H, Me), 1.63
(m, 4 H, 2 ϫ CH2), 2.27 (t, J ϭ 8 Hz, 2 H, CH2CN), 2.30 (t, J ϭ
commercial.
2-Oxazolines 3(a؊f)(a؊b). General Procedure: Finely powdered
carboxylic acid (10 mmoles) and β-amino alcohol (10 mmoles) were
placed in a Pyrex flask in such a way as to occupy only 10% of the
overall volume. The mixture was irradiated using the mode and
power indicated in Table 2 and monitored by TLC. When the ir-
radiation was performed in a domestic oven, the sample was placed
in the hottest zone of the oven, previously determined after careful
cartography of the oven.[29] When the irradiation was performed in
the monomode reactor the reaction mixture was mechanically
stirred for better homogenization. When all the starting material
had disappeared, the irradiation was terminated and the mixture
was allowed to cool to room temperature. Diethyl ether was added
and the resulting mixture was filtered. The solid oxazoline was
further washed with diethyl ether and recrystallized from the ap-
propriate solvent.
8 Hz, 2 H, CH2COO), 3.99 (d, J ϭ 9 Hz, 4 H, 2 ϫ 5-H), 4.02 (d,
J ϭ 11 Hz, 2 H, CH2OCO).C40H77NO3: calcd. C 77.48, H 12.52,
N 2.26; found C 77.50, H 12.45, N1.99.
2-Oxazolines 3(a؊i)c. General Procedure: Zinc oxide (47.4 g,
580 mmol) was added to a round-bottomed flask containing a solu-
tion of the carboxylic acid (20 mmoles) in an aprotic solvent
(50 mL of CH2Cl2, EtOAc or Et2O depending on the case). A solu-
tion of the amino alcohol 2c (30 mmol) in the same solvent (50 mL)
was added to the vigorously stirred mixture. The mixture was
further stirred at room temperature for a few minutes and then the
solvent was evaporated until total dryness. The resulting solid was
powdered and introduced into a Pyrex flask in such a way as to
occupy only 10% of the overall volume. The mixture was then ir-
radiated using the mode and power indicated in Table 3 and moni-
tored by TLC. When the irradiation was performed in the monom-
ode reactor the sample was mechanically stirred for better homo-
genization. When all the starting material had disappeared, the ir-
radiation was terminated and the mixture was allowed to cool to
room temperature. Ethyl acetate was added and the resulting mix-
ture was centrifuged. The clear liquid was taken out and the process
repeated at least twice. The liquid phases were collected and filtered
through a pad of SiO2/Al2O3 (1:1 w/w) to remove the last traces of
zinc oxide. The filtrate was concentrated to give the pure oxazo-
line derivative.
[2-(2-Chlorophenyl)-4,5-dihydro-1,3-oxazole-4,4-diyl]dimethanol
(3da): Mol. mass 241.68; 80% yield (1.93 g); m.p. 136Ϫ137 °C (iso-
propyl alcohol) (ref.[30] 138Ϫ139 °C). IR (KBr, cmϪ1): ν˜ ϭ 3428
1
(OH), 1653 (CϭN). H NMR (250 MHz, [D6]DMSO, ppm): δ ϭ
3.47 (br. s, 4 H, 2 ϫ CH2OH), 4.32 (s, 2 H, 2 ϫ 5-H), 7.48Ϫ7.86
(m, 4 H, Ar-H). 13C NMR (50 MHz, [D6]DMSO, ppm): δ ϭ 63.9,
70.8, 78.2, 127.3, 127.7, 129.3, 130.1, 130.3, 132.4, 161.2 (2 ϫ C).
C11H12ClNO3: calcd. C 54.67, H 5.00, N 5.80, Cl 14.67; found C
54.37, H4.85, N 5.81, Cl 14.74.
[2-(3-Chlorophenyl)-4,5-dihydro-1,3-oxazole-4,4-diyl]dimethanol
(3ea): Mol. mass 241.68; 80% yield (1.93 g); m.p. 114Ϫ115 °C (iso-
propyl alcohol) (ref.[30] 113Ϫ115 °C). IR (KBr, cmϪ1): ν˜ ϭ 3428
(OH), 1633 (CϭN). 1H NMR (250 MHz, CDCl3, ppm): δ ϭ
2.5Ϫ3.5 (m, 2 H, 2 ϫ OH), 3.73 (d, J ϭ 12 Hz, 4 H, 2 ϫ CH2OH),
4.38 (s, 2 H, 2 ϫ 5-H), 7.2Ϫ7.8 (m, 4 H, Ar-H). 13C NMR
(50 MHz, [D6]DMSO, ppm): δ ϭ 63.9, 70.8, 77.2, 127.3, 127.7,
129.3, 130.1, 130.3, 132.4, 161.2 (2 ϫ C).
2-(2-Furyl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole (3bc): Mol. mass
165.19; 83% yield (2.74 g). IR (CHCl3, cmϪ1): ν˜ ϭ 1672 (CϭN).
1H NMR (200 MHz, CDCl3, ppm): δ ϭ 1.35 (s, 6 H, 2 ϫ Me),
4.06 (s, 2 H, 2 ϫ 5-H), 6.45 (m, 1 H, Fur-H), 6.91 (d, J ϭ 3.4 Hz,
1 H, Fur-H), 7.5 (d, J ϭ 1 Hz, 1 H, Fur-H). 13C NMR (50 MHz,
CDCl3, ppm): δ ϭ 28.1, 67.4, 78.9, 111.2, 113.8, 142.9, 144.8, 154.5
(2 C). HRMS (EI): calcd. for C9H11NO2: 165.078979; found
165.079720.
[2-(4-Chlorophenyl)-4,5-dihydro-1,3-oxazole-4,4-diyl]dimethanol
(3fa): Mol. mass 241.68; 95% yield (2.3 g); mp. 178Ϫ179 °C (iso-
propyl alcohol) (ref.[31] 177Ϫ178 °C). IR (KBr, cmϪ1): ν˜ ϭ 3428
4,5-Dihydro-2-(4-methoxyphenyl)-4,4-dimethyl-1,3-oxazole
(3gc):
Mol. mass 205.26; 91% yield (3.74 g). IR (CHCl3, cmϪ1): ν˜ ϭ 1645
1
(CϭN). H NMR (200 MHz, CDCl3, ppm): δ ϭ 1.35 (s, 6 H, 2 ϫ
1
(OH), 1642 (CϭN). H NMR (250 MHz, [D6]DMSO, ppm): δ ϭ
Me), 3.82 (s, 3 H, OMe), 4.06 (s, 2 H, 2 ϫ 5-H), 6.88 (d, J ϭ 9 Hz,
1 H, Ar-H), 7.86 (d, J ϭ 9 Hz, 1 H, Ar-H). 13C NMR (50 MHz,
CDCl3, ppm): δ ϭ 28.1, 55.1, 67.3, 78.9 (2 C), 113.5, 115.7, 120.4
(2 C), 129.8, 161.8 (2 C). HRMS (EI): calcd. for C12H15NO2:
205.110279; found 205.108467.
3.76 (d, J ϭ 11 Hz, 4 H, 2 ϫ CH2OH), 4.40 (s, 2 H, 2 ϫ 5-H), 7.4
(d, J ϭ 11 Hz, 2 H, 2 ϫ Ar-H), 7.84 (d, J ϭ 11 Hz, 2 H, 2 ϫ Ar-
H). 13C NMR (50 MHz, [D6]DMSO, ppm): δ ϭ 63.9, 70.8, 77.1,
126.5 (2 ϫ C), 127.7 (2 ϫ C), 130.4, 135.9, 161.3 (2 ϫ C).
(2-Heptadecyl-4,5-dihydro-1,3-oxazole-4,4-diyl)di(methylene)
Di-
4,5-Dihydro-4,4-dimethyl-2-(4-nitrophenyl)-1,3-oxazole (3hc): Mol.
mass 220.23; 76% yield (3.35 g); mp. 90Ϫ91.5 °C (CHCl3, cmϪ1).
IR (CHCl3): ν˜ ϭ 1649 (CϭN), 1525 (NO2), 1351 (NO2). 1H NMR
(200 MHz, CDCl3): δ ϭ 1.39 (s, 6 H, 2 ϫ Me), 4.15 (s, 2 H, 2 ϫ
5-H), 8.09 (d, J ϭ 9 Hz, 1 H, Ar-H), 8.24 (d, J ϭ 9 Hz, 1 H, Ar-
H). 13C NMR (50 MHz, CDCl3, ppm): δ ϭ 28.2, 68.1, 79.5 (2 C).
123.3 (2 C), 129.1, 133.8, 149.3, 160.2 (2 C). C11H12N2O3: calcd. C
59.99, H 5.49, N 12.72; found C 59.76, H 5.29, N 12.59.
octadecanoate (3cabis): Mol. mass 902.54; 97% yield (8.75 g); m.p.
83Ϫ84 °C (CHCl3/MeOH, 1:1). IR (KBr, cmϪ1): ν˜ ϭ 1740 (CϭO),
1
1668 (CϭN). H NMR (250 MHz, CDCl3, ppm): δ ϭ 0.9 (t, 9 H,
J ϭ 7 Hz, 3 ϫ Me), 1.26 (m, 84 H, 42 ϫ CH2), 1.60 (m, 6 H, 3 ϫ
CH2), 2.3 (t, J ϭ 8 Hz, 2 H, CH2CN), 2.32 (t, J ϭ 8 Hz, 2 H,
CH2CO), 4.08 (s, 2 H, 2 ϫ 5-H), 4.14 (d, J ϭ 11 Hz, 4 H,
CH2OCO). C57H109NO5: calcd. C 77.19, H 12.40, N 1.55; found C
77.66, H 12.49, N 1.47.
(4-Methyl-4,5-dihydro-2-phenyl-1,3-oxazol-4-yl)methyl
(3ab): Mol. mass 295.34; 96% yield (2.84 g); m.p. 45Ϫ47 °C (isopro-
Benzoate
4,5-Dihydro-4,4-dimethyl-2-pentadecyl-1,3-oxazole (3ic): Mol. mass
1
309.54; 84% yield (5.2 g). IR (CHCl3, cmϪ1): ν˜ ϭ 1664 (CϭN). H
4390
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Eur. J. Org. Chem. 2003, 4387Ϫ4391

Solvent-Free Microwave-Assisted Efficient Synthesis of 4,4-Disubstituted 2-Oxazolines
FULL PAPER
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1.22 (br. s, 30 H, 12 ϫ CH2 and 2 ϫ Me), 1.57 (m, 2 H, CH2), 2.20
(t, J ϭ 7 Hz, 2 H, CH2CN) 3.85 (s, 2 H, 2 ϫ 5-H). 13C NMR
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Acknowledgments
Part of this work was sponsored from 1993 to 1999 by the French-
Cuban cooperation within the framework of the agreement CNRS:
MINVEC (ref. 5702). We sincerely thank these organisations for
their help. Part of this work was supported by the Spanish Minis-
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terio de Ciencia y Tecnologıa (PB9820443-C02202), the Canary Is-
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´
´
lands Consejerıa de Educacion y Ciencia (COFI2000/03) and the
FEDER (1SD9720747-C4201). A. L. M. T. Thanks to The Third
World Academy of Sciences for an equipment budget (research
grant N°94-209 RG/CHE/LA), to Universidad La Laguna for an
Intercampus Grant.
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