Regioselective synthesis of N-substituted 4-methylene-2-oxazolidinones and 4-oxazolin-2-ones. Study of reactivity in thermal Michael conjugate additions

Article abstract of DOI:10.1016/S0040-4020(00)00311-2

N-Substituted 4-methylene-2-isoxazolidinones 9a-9e have been prepared from the tandem condensation of isocyanates 3 with α-ketol 7. In a more polar solvent (DMF) the same reaction led to stereoisomeric alcohols 11 and 12, which could be transformed to the thermodynamically more stable isomers 4-oxazolin-2-ones 10 in good yield. Thermal conjugate additions of both heterocycles 9a and 10a to enone 13 provided the C-5 adduct 15. When the reaction was carried out with the captodative olefin 17, the unexpected aniline 18 was isolated. The regiochemistry of the Michael addition was rationalized in terms of FMO theory by ab initio calculations. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00311-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3857±3866
Regioselective Synthesis of N-Substituted
4-Methylene-2-oxazolidinones and 4-Oxazolin-2-ones.
Study of Reactivity in Thermal Michael Conjugate Additions
*
   Â
Rafael Martõnez, Hugo A. Jimenez-Vazquez and Joaquõn Tamariz
  Â
Departamento de Quõmica Organica, Escuela Nacional de Ciencias Biologicas, I.P.N. Prol. Carpio y Plan de Ayala,
11340 Mexico, DF, Mexico
Received 3 March 2000; accepted 19 April 2000
AbstractÐN-Substituted 4-methylene-2-isoxazolidinones 9a±9e have been prepared from the tandem condensation of isocyanates 3 with
a-ketol 7. In a more polar solvent (DMF) the same reaction led to stereoisomeric alcohols 11 and 12, which could be transformed to the
thermodynamically more stable isomers 4-oxazolin-2-ones 10 in good yield. Thermal conjugate additions of both heterocycles 9a and 10a to
enone 13 provided the C-5 adduct 15. When the reaction was carried out with the captodative ole®n 17, the unexpected aniline 18 was
isolated. The regiochemistry of the Michael addition was rationalized in terms of FMO theory by ab initio calculations. q 2000 Elsevier
Science Ltd. All rights reserved.
Introduction
considering that the hydroxy group would be the nucleo-
philic group, and the carbonyl group, the electron de®cient
center (Scheme 2). Isocyanates 3 would play the role of the
counterpart. These species may provide either 4-methylene-
2-oxazolidinones 9 or 4-oxazolin-2-ones 10, depending on
the orientation of the dehydration step, and if this could be
selective. The latter are useful synthons and precursors for a
variety of aldehydes, amino ketones, and alcohols.2 They
have also been used as protecting groups,3 and the N-aryl
5-t-butyl-4-chloro-4-oxazolin-2-ones derivatives have
signi®cant herbicide activity.4
We have recently developed a promising methodology for
the one-step synthesis of novel N-substituted exo-2-oxa-
zolidinone dienes 1, which involves a tandem condensation
of aliphatic a-diketones 2 to isocyanates 3, and intra-
molecular cyclization of the carbamate anion intermediate
4 to give the 4-hydroxy-5-methylene-oxazolidinone 5
(Scheme 1).1 Dehydration of the latter leads to dienes 1 in
fair yields. When the unsymmetrical a-diketone 2b was
treated under these conditions, dienes 1b were formed as a
single regio- and stereo-isomer.
Owing to the importance of these heterocycles, several
methodologies have been designed for their selective
synthesis,5 such as the cyclization of O-propargylic
carbamates catalyzed by metal ions,6 the condensation of
tertiary propargylic alcohols with isocyanates,7 reaction of
a-monosubstituted oximes with methyl carbonate,8 and
The versatility of this method might be further improved by
taking advantage of this cascade process with a new class of
substrate 6 that would bear, like the a-diketones 2, potential
nucleophilic and electrophilic centers. One could consider
3-hydroxy-2-butanone (7) as a synthetic equivalent of 6,
Scheme 1.
Keywords: 4-methylene-2-oxazolidinones; 4-oxazolin-2-ones; Michael addition; FMO theory.
* Corresponding author. Fax: 152-55866621; e-mail: jtamariz@woodward.encb.ipn.mx
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00311-2

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R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3858
Scheme 2.
introduction of carbon dioxide into acetylenic amines.9 To
the best of our knowledge, only two examples have been
reported using the reaction between a-hydroxy ketones and
isocyanates; however, they are limited to the preparation of
either 4-oxazolin-2-ones,10 or 4-methylene-5,5-dimethyl-2-
oxazolidinones.11
comparable results. We also investigated the effect of
Ê
molecular sieves (4 A) as an alternative dehydrating agent,
giving also the exocyclic ole®nic heterocycle in comparable
yield.
These compounds were fully characterized by spectroscopy,
and the structure of derivative 9b was also determined by
X-ray crystallography (Fig. 1). It is noteworthy that the
chemical shifts for the vinylic protons H-6a and H-6b are
reversed in comparison to those analogous to dienic protons
of 1a and 1b. Thus, in compounds 9, proton H-6a was
located down-®eld with respect to H-6b (ca. 0.1 ppm). In
comparison, for the corresponding protons of dienes 1, H-6a
was shielded up-®eld with respect to H-6b to a greater extent
(ca. 0.4 ppm), whatever the substituent be at the nitrogen
atom.
Herein, we report that the condensation and intramolecular
cyclization of a-ketol 7 with isocyanates 3 can be a very
ef®cient methodology for the regioselective preparation of
N-substituted 4-methylene-2-oxazolidinones 9, or N-substi-
tuted 4-oxazolin-2-ones 10, depending on the polarity of
the solvent. Additional information about the reactivity of
these compounds toward Michael acceptors, and the
possible role of frontier molecular orbitals in explaining
the regiochemistry, is also provided.
When a more polar solvent (DMF) was used, under similar
conditions of additive, temperature, and reaction time
(Li2CO3, 258C, 12 h), the reaction provided a mixture of
alcohols 11/12. Scheme 4 summarizes the results, showing
that the process was stereoselective, since the anti dimethyl
alcohol 11 was the major epimer. The structure was
established by nOe experiments, detecting an enhancement
of the signal of the methyl Me-4 when the proton H-5 was
irradiated. This assignment was con®rmed by X-ray crystal-
lography of alcohol 11d (Fig. 1).
Results and Discussion
The reaction of isocyanates 3a±3e with a-ketol 7 was found
to proceed smoothly under mild conditions (dioxane/
Li2CO3, room temperature, 12 h), similar to those used for
the preparation of dienes 1, to give N-substituted 4-methyl-
ene-2-oxazolidinones 9a±9e in fair yields (57±86%) as the
exclusive regioisomer (Scheme 3). The endocyclic isomeric
ole®n 10 was not detected in the crude reaction mixtures. An
increase of the temperature (1008C) does not seem to have a
signi®cant effect either on the outcome of the process, or
on the regiochemistry of the dehydration. The use of
another solvent of low polarity, such as toluene, furnished
The dehydration step was carried out by heating to re¯ux a
DMSO solution of the mixture of alcohols 11/12,12 yielding
almost quantitatively the endocyclic elimination products
Scheme 3.

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R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3859
Figure 1. X-Ray structures of compounds 9b, 10c, and 11d.
1
10 (Scheme 4). In the H and 13C NMR spectra of all the
treatment in high yield (Eq. (1)).
derivatives, the methyl group Me-6 on C-4 is shifted up-
®eld with respect to methyl group Me-7, as established by
nOe and HETCOR experiments. The X-ray structure of 10c
is depicted in Fig. 1.
The preference of the anti isomer 11 may be accounted for
possibly by thermodynamic control at the cyclization step.
The conformational intermediates 13a and 13b, which
derived from the ®rst addition of the alkoxide of 7 to iso-
cyanates 3, may be interconverting by C±C bond rotation,
the equilibrium being shifted to 13a, in order to maintain the
anti relationship of the methyl groups (Scheme 4).
ꢀ1†
According to the importance of the dehydrating agent
for the preparation of dienes 1,1a we investigated the
Ê
effect of molecular sieves (4 A) in the reaction of
alcohol 7 with isocyanates, in order to obtain the 4-oxazo-
lin-2-ones, 10, directly. Even though a small amount of
10 is formed, alcohols 11/12 remained largely the major
products.
The higher stability of regioisomer 10 has been con®rmed
by ab initio calculations (RHF/3-21G and 6-31Gp), showing
small differences of energy for the pairs 9a/10a, and 9e/10d
(Table 1). At the 6-31Gp level this difference is slightly
larger. Electron lone pair delocalization through the double
bond by both heteroatoms, nitrogen and oxygen, may be
invoked as the reason of this stabilization. The strain gener-
ated by the endo double bond, though, and the destabilizing
nonbonding van der Waals interactions between the methyl
groups in compounds 10, might be the origin of the relative
small differences in energy with respect to isomers 9.
The regioselectivity in the dehydration step by thermal
treatment with DMSO suggests a thermodynamic control,
consistent with a carbenium ion intermediate.12 In addition,
the direct formation of the exocyclic elimination products
9a±9e seems to be under kinetic control, since compound
9d was converted to the endo isomer 10e by acid catalyzed
Scheme 4.

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R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3860
Table 1. Relative electronic energies (DE, kcal/mol) for the pairs 9a/10a,
and 9e/10d, calculated by RHF/3-21G and 6-31Gp
The reaction was highly regioselective, in view of the
presence of a single product, since the alternative adduct
16, arising from the addition of C-4 to electrophile 13,
was not detected in the crude reaction mixture. The
nOe experiments carried out in compound 15 showed
that the double bond was placed at the C-4 position, as a
consequence of the enhancement of the phenyl group
signal when the ole®nic proton H-6a was irradiated. The
structure of 15 was con®rmed by X-ray crystallography
(Scheme 5).
DE (9a±10a)
DE (9e±10d)
3-21G
6-31Gp
0.47
1.72
0.05
1.24
Considering the relative stability of the double bond in
isomers 9 and 10, and the fact that it may be considered
as a part of both an enamide and an enol ester moiety, we
examined the reactivity of these compounds with conjugate
acceptors. Thermal (1508C, 24 h) addition of 10a to methyl
vinyl ketone (13) led to the conjugate adduct 15 in 83%
yield, as a colorless crystalline product (Scheme 5). This
product would arise from zwitterion 14, that is later
stabilized by proton abstraction from the C-6 methyl, and
by proton enolate trapping. Further heating to high
temperature (2508C, 24 h) of 15 failed to promote internal
cyclization, recovering the starting material.
Similarly, addition of isomer 9a to 13, under analogous
reaction conditions, gives rise to the same adduct 15 in
76% yield. This result may be accounted for as a conse-
quence of a previous thermal isomerization of the exo
double bond to the endo position to give isomer 10a. The
isomerization process seems to be faster than the addition to
enone 13, since lower reaction temperatures (1008C) did not
prevent the slow conversion to isomer 10a, but under these
conditions the addition did not take place.
Scheme 5.
Scheme 6.

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R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3861
The captodative ole®n 3-(p-nitrobenzoyloxy)-3-buten-2-
one (17) has proven to be a very reactive dienophile,13
and dipolarophile14 in cycloaddition reactions. Oxazolinone
10a reacted with ole®n 17 in xylene at 1808C for 24 h to
yield a mixture of two main products: diarylamine 18, and
the dimeric product of the ole®n, 1915 (Scheme 6). The
former product was likely formed by a consecutive series
of reactions, including the intramolecular nucleophilic addi-
tion of the enamide moiety to the carbonyl group of 20, the
®rst formed adduct by Michael addition, to give a series of
intermediate species 21, 22, and 23, successively.16 The
latter gives rise to 18 after losing water. It is surprising to
see that this kind of product was not observed in the reaction
with 13.
sponding coef®cients for each one of them. In addition,
the same parameters for enones 13 and 17 are included.17
Geometries were fully optimized using the AM1 semi-
empirical method18 and employed as the starting point for
ab initio optimization, using the 3-21G and 6-31Gp basis
sets.19 From the FMO energies, it appears that the
HOMO-heterocycle/LUMO-ole®n interaction is preferred
(Table 3). Moreover, in principle, the endo-double bond
heterocycles 10a and 10d should be more reactive than
isomers 9a and 9e, respectively, due to a smaller energy
gap between the interacting FMOs (i.e. the HOMOs of
compounds 9 are more stable, see Table 2). In contrast to
the values shown in Table 3, where the HOMO-10/LUMO-
17 energy gaps are smaller than those for ole®n 13, the
reactivity of ole®n 17 was lower, since any conversion of
starting material takes place below 1808C.
Other Michael acceptors, such as methyl propiolate (24),
methyl acrylate (25), and tetracyanoethylene (26), were
submitted to the same addition conditions with 10a,
however, none of the expected reaction products were
detected. Starting materials were recovered, along with a
dense dark residue, seemingly coming from the ole®n
polymerization.
On the basis of coef®cient differences for the proper
frontier orbital interaction between heterocycle 10 and
Michael acceptor (HOMO-heterocycle/LUMO-ole®n),
regioselectivity could be assessed. It can be observed that
the relative value of the coef®cient C2 on C-5 is bigger than
C1 on carbon C-4 in the HOMO of both 10a and 10d. The
lower electronegativity and higher releasing effect of the
nitrogen lone pair, in comparison with the oxygen atom,
would explain the polarization of the p-system. Therefore,
the main interaction to be predicted is that between carbon
C-5 of heterocycle 10 with the terminal carbon C-1 of
ole®ns 13 and 17, since the largest LUMO coef®cients of
the latter are located on this carbon (Fig. 2).
Given the enamide and enol ester character of the double
bond, and the fact that both heteroatoms polarize the double
bond in the opposite direction in compounds 10, these
experiments would support the hypothesis of a stronger
effect from the nitrogen atom in Diels±Alder additions.1a
This is probably due to the higher polarizability of the
nitrogen lone pair. In order to evaluate this by a theoretical
method, we calculated the energy of the MOs for the exo-
and endo-ole®nic heterocycles 9a/10a, and 9e/10d. Table 2
summarizes the HOMO/LUMO energies and the corre-
A lower reactivity found in methyl propiolate (24) and
methyl acrylate (25) with respect to 13 and 17 may be due
Table 2. Ab initio 3-21G and 6-31Gp calculations of energies (eV) and coef®cients (Ci) of the Frontier Molecular Orbitals for heterocycles 9a, 9e, 10a, and 10d,
0
and ole®ns MVK (13) and 17. These are the values of the 2pz coef®cients, the relative 2pz contributions and their DCi are analogous. For the calculations of
ole®ns 13 and 17 see Ref. 17.
HOMOa
LUMOb
Compdc
9a
Level
E(eV)
C1
C2
DCid
E(eV)
C1
C2
DCid
3-21G
6-31Gp
3-21G
6-31Gp
3-21G
6-31Gp
3-21G
6-31Gp
3-21G
6-31Gp
3-21G
6-31Gp
28.8440
28.9132
29.4710
29.3891
28.5058
28.3736
28.7409
28.6846
210.5391
210.4895
211.0460
211.0123
20.2322
20.2991
20.3060
0.3650
20.2497
0.2768
20.2437
0.2943
0.2935
20.3464
20.2991
20.3593
20.1405
20.1934
20.2014
0.2417
20.2888
0.3283
20.2875
0.3426
0.3031
20.3669
20.2873
20.3565
0.0917
0.1057
0.1046
4.5762
4.6382
4.2284
4.2733
5.2630
5.3190
4.8450
4.8426
2.9002
2.9222
2.2417
2.4588
0.2437
0.2804
0.2506
0.2785
0.3203
0.3623
0.2813
0.2516
20.2690
0.3109
0.2548
0.2940
20.3004
20.3635
20.3176
20.3729
20.3291
20.3708
20.2893
20.2545
0.1745
20.0567
20.0831
20.0670
20.0944
20.0088
20.0085
20.0080
20.0029
0.0945
9e
0.1233
10a
10d
13
20.0391
20.0515
20.0438
20.0483
20.0096
20.0205
0.0118
20.2069
20.1972
20.2386
0.1040
0.0576
0.0554
17
0.0028
a Energies and coef®cients of 2NHOMOs of ole®n 17, since the HOMOs and NHOMOs do not have a pz contribution.
b Energies and coef®cients of 2NLUMOs of 9a, and 10a, and NLUMO of 17, since the LUMOs do not have a pz contribution, at the 3-21G and 6-31Gp levels.
c The FMOs of the most stable non-planar s-trans conformation for 17 and s-cis for 13.
d Carbon 1±carbon 2 for the double bonds.

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3862
Table 3. Energy gaps (eV) of frontier orbitals for heterocycles 10a and 10d and ole®ns 13 and 17
Heterocycle
Method
13a
17a
HOMO±LUMO
LUMO±HOMO
HOMO±LUMO
LUMO±HOMO
10a
10d
3-21G
6-31Gp
3-21G
6-31Gp
11.4060
11.2958
11.6411
11.6068
15.8021
15.8085
15.3841
15.3321
10.7475
10.8324
10.9826
11.1434
16.3090
16.3313
15.8910
15.8549
a HOMO-heterocycle/LUMO-ole®n and LUMO-heterocycle/HOMO-ole®n. The gaps for ole®n 17 were calculated with the 2NHOMO, since its HOMO
does not have any pz contribution in the ole®n, and 2NLUMOs of 10a, and NLUMO of 17, in both levels.
Figure 2. Ab initio RHF/6-31Gp frontier orbital interactions for the Michael addition of 10a with ole®ns 13 and 17.
to less stable LUMOs for the former compounds.1a
Although this argument could not be invoked for the case
of tetracyanoethylene (26), however, steric factors might be
controlling the approach of this electrophile toward the
already crowded nucleophilic C-5 quaternary center of 10.
This is also suggested by the reactivity differences between
13 and 17, the latter being the less reactive ole®n, though its
LUMO is the most stable (Table 2).
Electrothermal capillary melting point apparatus. IR spectra
were recorded on a Perkin±Elmer 1600 spectrophotometer.
1H and 13C NMR spectra were obtained on a Varian Gemini-
300 (300 MHz) instrument, with CDCl3 as solvent and TMS
as internal standard. The mass spectra (MS) were taken on a
Hewlett±Packard 5971A spectrometer. X-Ray crystallo-
graphic structures were obtained on a Siemens P4 diffract-
ometer.20 Microanalyses were performed by M-H-W
Laboratories (Phoenix, AZ). All air moisture sensitive
reactions were carried out under nitrogen using oven-dried
glassware. Dioxane, ethyl ether, toluene, and xylene were
freshly distilled from sodium; methylene chloride, DMF,
and DMSO from calcium hydride prior to use. Li2CO3
was dried overnight at 1208C before use. All other reagents
were used without further puri®cation.
Conclusion
A new series of 4-methylene-2-oxazolidinones 9a±9e,
and 4-oxazolin-2-ones 10a±10e, have been prepared from
3-hydroxy-2-butanone (7) in the presence of isocyanates 3,
using a regioselective methodology. The polarity of the
solvent seems to play an important role in the formation
of either heterocycles 9 or the alcohol precursors 11/12,
that are selectively dehydrated to the endo ole®nic hetero-
cycle 10. These results contribute to con®rm the tandem
pathway between two potential dipolar species as a versatile
strategy for the preparation of functionalized heterocycles
related to cyclic carbamates. These compounds proved to be
ef®cient nucleophilic enamides before the presence of some
Michael acceptor enones. The regioselectivity shown by
10a and 10d was rationalized by FMO calculations, which
showed a good ®t between the proper coef®cients in both
reactants for the most stable HOMO-heterocycle/LUMO-
ole®n interaction.
General procedure for the preparation of N-substituted
5-methyl-4-methylene-2-oxazolidinones, 9a±9e
A solution of 3-hydroxy-2-butanone (7) (0.31 g, 3.5 mmol)
in dry dioxane (3 mL) was added to a suspension of triethyl-
amine (0.70 g, 7.0 mmol) and dry Li2CO3 (0.31 g,
4.2 mmol) in dry dioxane (2 mL), under an N2 atmosphere
and at room temperature. The mixture was stirred for
30 min, and a solution of the isocyanate 3 (5.2 mmol) in
dry dioxane (2 mL) was added dropwise. The mixture was
stirred for 12 h at room temperature, ®ltered, and the solvent
was removed under vacuum. The residue was puri®ed by
column chromatography on silica gel treated with triethyl-
amine (10%) in hexane (30 g per gram of crude) (hexane/
EtOAc, 9:1).
Experimental
5-Methyl-4-methylene-N-phenyl-2-oxazolidinone (9a).
Using the general procedure with 0.62 g of 3a gave 0.43 g
(67%) of 9a as colorless crystals (hexane/CH2Cl2, 3:7):
Rf 0.51 (hexane/EtOAc, 7:3); mp 87±888C [lit.21
General
Melting points (uncorrected) were determined with an

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R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3863
89.5±90.58C], IR (KBr) 1759, 1646, 1390, 1318, 1195,
EtOAc, 7:3); IR (KBr) 2974, 1769, 1671, 1441, 1405, 1344,
1190, 1072, 1031, 815 cm21; 1H NMR (300 MHz, CDCl3) d
1.41 (d, Jˆ6.5 Hz, 3H, Me-7), 3.57±3.64 (m, 2H, H-8),
3.67±3.74 (m, 2H, H-9), 4.01±4.05 (m, 1H, H-6b), 4.14±
4.18 (m, 1H, H-6a), 4.98±5.06 (m, 1H, H-5); 13C NMR
(75.4 MHz, CDCl3) d 20.7 (C-7), 39.0 (C-8), 42.4 (C-9),
74.7 (C-5), 80.4 (C-6), 145.7 (C-4), 155.8 (C-2); MS (70
eV) 177 (M112, 9), 175 (M1, 30), 126 (41), 113 (52), 104
(30), 63 (37), 42 (100). Anal. Calcd for C7H10ClNO2: C,
47.88; H, 5.74; N, 7.98. Found: C, 47.65; H, 5.89; N, 7.82.
1
1072, 754, 692 cm21; H NMR (300 MHz, CDCl3) d 1.60
(d, Jˆ6.4 Hz, 3H, Me-7), 4.08 (dd, Jˆ2.8, 2.0 Hz, 1H,
H-6b), 4.19 (dd, Jˆ2.8, 2.5 Hz, 1H, H-6a), 5.20±5.30 (m,
1H, H-5), 7.33±7.55 (m, 5H, PhH); 13C NMR (75.4 MHz,
CDCl3) d 21.0 (C-7), 74.9 (C-5), 81.8 (C-6), 126.8 (C-9),
128.1 (C-11), 129.4 (C-10), 133.8 (C-8), 147.4 (C-4), 155.1
(C-2); MS (70 eV) 189 (M1, 66), 143 (20), 144 (39), 130
(100), 103 (21), 77 (44). Anal. Calcd for C11H11NO2: C,
69.83; H, 5.86; N, 7.40. Found: C, 69.77; H, 5.93; N, 7.63.
N-( p-Chlorophenyl)-5-methyl-4-methylene-2-oxazolidi-
none (9b). Using the general procedure with 0.80 g of 3b
gave 0.46 g (61%) of 9b as colorless crystals (hexane/
CH2Cl2, 3:7): Rf 0.52 (hexane/EtOAc, 7:3); mp 102±
1038C, IR (KBr) 1715, 1591, 1489, 1393, 1224, 1173,
General procedure for the preparation of N-substituted
4-hydroxy-4,5-dimethyl-2-oxazolidinones, 11a±11d and
12a±12d
A solution of 3-hydroxy-2-butanone (7) (0.31 g, 3.5 mmol)
in dry DMF (3 mL) was added to a suspension of triethyl-
amine (0.70 g, 7.0 mmol) and dry Li2CO3 (0.31 g,
4.2 mmol) in dry DMF (2 mL), under an N2 atmosphere
and at room temperature. The mixture was stirred for
30 min, and a solution of the isocyanate 3 (5.2 mmol) in
dry DMF (2 mL) was added dropwise. The mixture was
stirred for 12 h at room temperature, ®ltered, and the solvent
was removed under vacuum. The residue was puri®ed by
column chromatography on silica gel treated with triethyl-
amine (10%) in hexane (30 g per gram of crude) (hexane/
EtOAc, 9:1).
1
1088, 817 cm21; H NMR (300 MHz, CDCl3) d 1.61 (d,
Jˆ6.4 Hz, 3H, Me-7), 4.11 (dd, Jˆ2.8, 2.2 Hz, 1H, H-6b),
4.20 (dd, Jˆ2.8, 2.4 Hz, 1H, H-6a), 5.18±5.26 (m, 1H, H-5),
7.22±7.29 (m, 2H, ArH), 7.38±7.44 (m, 2H, ArH); 13C
NMR (75.4 MHz, CDCl3) d 21.1 (C-7), 75.1 (C-5), 82.1
(C-6), 128.3 (C-9), 129.8 (C-10), 132.5 (C-8), 134.0
(C-11), 147.3 (C-4), 154.7 (C-2); MS (70 eV) 225
(M112, 17), 223 (M1, 52), 178 (12), 166 (33), 164 (100),
144 (51), 137 (62), 111 (31), 102 (15), 75 (25). Anal. Calcd
for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C,
59.14; H, 4.64; N, 6.40.
(4Rp,5Sp)-4-Hydroxy-4,5-dimethyl-N-phenyl-2-oxazolidi-
none (11a). (4Rp,5Rp)-4-Hydroxy-4,5-dimethyl-N-phenyl-
2-oxazolidinone (12a). Using the general procedure with
0.62 g of 3a gave a mixture of 11a/12a (76:24), which
after recrystallization (hexane/CH2Cl2, 1:1) yielded 0.39 g
(56%) of 11a as colorless crystals: Rf 0.55 (hexane/EtOAc,
1:1); mp 97±998C, IR (KBr) 3310, 1728, 1647, 1593, 1495,
1233, 1162, 759, 694 cm21; 1H NMR (300 MHz, CDCl3) d
1.29 (d, Jˆ6.6 Hz, 3H, Me-7), 1.35 (s, 3H, Me-6), 4.42 (q,
Jˆ6.6 Hz, 1H, H-5), 4.98 (br s, 1H, OH), 7.25±7.50 (m, 5H,
PhH). Signals attributed to minor isomer 12a: 1.31 (d,
Jˆ6.6 Hz, Me-7), 1.34 (s, Me-6), 4.49 (q, Jˆ6.6 Hz, H-5);
13C NMR (75.4 MHz, CDCl3) d 12.5 (C-7), 23.2 (C-6), 80.9
(C-5), 89.2 (C-4), 127.2 (C-9), 127.3 (C-11), 128.8 (C-10),
134.7 (C-8), 156.8 (C-2). MS (70 eV) 207 (M1, 19), 189
(19), 164 (4), 120 (100), 92 (20), 77 (52). Anal. Calcd for
C11H13NO3: C, 63.76; H, 5.87; N, 6.27; Found: C, 63.88; H,
5.79; N, 6.51.
5-Methyl-4-methylene-N-(p-tolyl)-2-oxazolidinone (9c).
Using the general procedure with 0.69 g of 3c gave 0.40 g
(57%) of 9c as colorless crystals (hexane/CH2Cl2, 3:7): Rf
0.52 (hexane/EtOAc, 7:3); mp 72±738C, IR (KBr) 1757,
1
1649, 1514, 1405, 1322, 1208, 1079, 980, 819 cm21; H
NMR (300 MHz, CDCl3) d 1.61 (d, Jˆ6.6 Hz, 3H, Me-7),
2.39 (s, 3H, CH3Ar), 4.03 (dd, Jˆ2.8, 2.2 Hz, 1H, H-6b),
4.16 (dd, Jˆ2.7, 2.4 Hz, 1H, H-6a), 5.19±5.26 (m, 1H, H-5),
7.19±7.33 (m, 4H, ArH); 13C NMR (75.4 MHz, CDCl3) d
21.1 (C-7 or CH3Ar), 21.2 (CH3Ar or C-7), 75.0 (C-5), 79.2
(C-6), 126.8 (C-9), 130.2 (C-10), 131.1 (C-8), 138.4 (C-11),
147.8 (C-4), 155.4 (C-2); MS (70 eV) 203 (M1, 63), 158
(24), 144 (100), 117 (43), 91 (35), 65 (23). Anal. Calcd for
C12H13NO2: C, 70.91; H, 6.45; N, 6.89. Found: C, 70.74; H,
6.52; N, 6.89.
N-(p-Anisyl)-5-methyl-4-methylene-2-oxazolidinone (9d).
Using the general procedure with 0.77 g of 3d gave 0.52 g
(69%) of 9d as colorless crystals (hexane/CH2Cl2, 3:7): Rf
0.49 (hexane/EtOAc, 7:3); mp 77±788C, IR (KBr) 1767,
(4Rp,5Sp)-N-( p-Chlorophenyl)-4-hydroxy-4,5-dimethyl-
2-oxazolidinone (11b). (4Rp,5Rp)-N-( p-Chlorophenyl)-4-
hydroxy-4,5-dimethyl-2-oxazolidinone (12b). Using the
general procedure with 0.80 g of 3b gave a mixture of
11b/12b (80:20), which after recrystallization (hexane/
CH2Cl2, 1:1) yielded 0.51 g (62%) of 11b as colorless
crystals: Rf 0.47 (hexane/EtOAc, 1:1); mp 105±1068C, IR
(KBr) 3369, 1732, 1490, 1392, 1232, 1150, 1083 cm21; 1H
NMR (300 MHz, CDCl3) d 1.28 (d, Jˆ6.6 Hz, 3H, Me-7),
1.34 (s, 3H, Me-6), 4.40 (q, Jˆ6.6 Hz, 1H, H-5), 4.91 (br s,
1H, OH), 7.27±7.35 (m, 4H, ArH). Signals attributed to
minor isomer 12b: 1.31 (s, Me-6), 4.48 (q, Jˆ6.5 Hz,
H-5), 5.10 (br s, OH); 13C NMR (75.4 MHz, CDCl3) d
12.5 (C-7), 23.1 (C-6), 81.1 (C-5), 89.3 (C-4), 128.0
(C-9), 129.0 (C-10), 133.1 (C-11), 133.2 (C-8), 156.7
(C-2); MS (70 eV) 241 (M1, 1), 225 (10), 223 (30), 154
1
1514, 1402, 1243 cm21; H NMR (300 MHz, CDCl3) d
1.61 (d, Jˆ6.4 Hz, 3H, Me-7), 3.83 (s, 3H, MeOAr), 4.05
(ddd, Jˆ2.6, 2.0, 0.7 Hz, 1H, H-6b), 4.12 (dd, Jˆ2.6,
2.4 Hz, 1H, H-6a), 5.20±5.28 (m, 1H, H-5), 6.97±7.00 (m,
2H, ArH), 7.22±7.27 (m, 2H, ArH); 13C NMR (75.4 MHz,
CDCl3) d 21.2 (C-7), 55.5 (MeO), 74.9 (C-5), 81.6 (C-6),
114.9 (C-10), 126.5 (C-8), 128.4 (C-9), 148.2 (C-4), 155.8
(C-2), 159.4 (C-11); MS (70 eV) 219 (M1, 17), 160 (6), 148
(100), 111 (9), 92 (15), 77 (25). Anal. Calcd for C12H12NO3:
C, 65.78; H, 5.98; N, 6.39. Found: C, 65.90; H, 6.08; N,
6.55.
N-(2-Chloroethyl)-5-methyl-4-methylene-2-oxazolidinone
(9e). Using the general procedure with 0.55 g of 3e gave
0.52 g (86%) of 9e as a pale brown oil: Rf 0.62 (hexane/

Â
R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3864
(34), 152 (100), 113 (12), 111 (29), 75 (22). Anal. Calcd for
C12H15NO3: C, 54.67; H, 5.01; N, 5.80; Found: C, 54.67; H,
5.40; N, 6.03.
44), 144 (33), 130 (100), 119 (9), 103 (34), 91 (9), 77
(71). Anal. Calcd for C11H11NO2: C, 69.83; H, 5.86; N,
7.40. Found: C, 69.90; H, 6.07; N, 7.60.
(4Rp,5Sp)-4-Hydroxy-4,5-dimethyl-N-( p-tolyl)-2-oxazoli-
dinone (11c). (4Rp,5Rp)-4-Hydroxy-4,5-dimethyl-N-( p-
tolyl)-2-oxazolidinone (12c). Using the general procedure
with 0.69 g of 3c gave a mixture of 11c/12c (77:23), which
after recrystallization (hexane/CH2Cl2, 1:1) yielded 0.54 g
(72%) of 11c as colorless crystals: Rf 0.57 (hexane/EtOAc,
7:3); mp 110±1118C, IR (KBr) 3325, 2916, 1740, 1626,
N-(p-Chlorophenyl)-4,5-dimethyl-4-oxazolin-2-one (10b).
Using the general procedure with 0.35 g of 11b/12b (80:20)
gave 0.31 g (97%) of 10b as colorless crystals (hexane/
CH2Cl2, 1:1): Rf 0.32 (hexane/EtOAc, 7:3); mp 125±
1268C, IR (KBr) 1747, 1706, 1495, 1382, 1248, 1186,
1
1083, 985, 830 cm21; H NMR (300 MHz, CDCl3) d 1.86
(br s, 3H, Me-6), 2.10 (br s, 3H, Me-7), 7.17±7.28 (m, 2H,
ArH), 7.33±7.46 (m, 2H, ArH); 13C NMR (75.4 MHz,
CDCl3) d 8.9 (C-6), 10.1 (C-7), 117.6 (C-4), 128.1 (C-9),
129.7 (C-10), 132.6 (C-5 or C-8), 132.7 (C-8 or C-5), 134.0
(C-11), 154.3 (C-2); MS (70 eV) 225 (M112, 16), 223 (M1,
48), 178 (3), 152 (100), 111 (27), 75 (29). Anal. Calcd for
C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C, 59.30;
H, 4.75; N, 6.50.
;
1588, 1271, 1223, 1088 cm21 1H NMR (300 MHz,
CDCl3) d 1.30 (d, Jˆ6.6 Hz, 3H, Me-7), 1.33 (s, 3H,
Me-6), 2.36 (s, 3H, CH3Ar), 4.41 (q, Jˆ6.6 Hz, 1H, H-5),
4.64 (br s, 1H, OH), 7.13±7.27 (m, 4H, ArH). Signals attri-
buted to minor isomer 12c: 4.46 (q, Jˆ6.6 Hz, H-5), 5.00 (br
s, OH); 13C NMR (75.4 MHz, CDCl3) d 12.7 (C-7), 21.1
(C-12), 23.4 (C-6), 80.8 (C-5), 89.1 (C-4), 127.3 (C-9),
129.5 (C-10), 131.9 (C-8), 135.2 (C-11), 156.8 (C-2); MS
(70 eV) 221 (M1, 33), 134 (100), 106 (83), 91 (20), 77 (23).
Anal Calcd for C12H15NO3: C, 65.14; H, 6.83; N, 6.33.
Found: C, 65.03; H, 6.91; N, 6.48.
4,5-Dimethyl-N-( p-tolyl)-4-oxazolin-2-one (10c). Using
the general procedure with 0.32 g of 11c/12c (77:23) gave
0.35 g (80%) of 10c as colorless crystals (hexane/CH2Cl2,
3:7): Rf 0.61 (hexane/EtOAc, 7:3); mp 64±658C, IR (KBr)
(4Rp,5Sp)-N-(2-Chloroethyl)-4-hydroxy-4,5-dimethyl-2-
oxazolidinone (11d). (4Rp,5Rp)-N-(2-Chloroethyl)-4-hy-
droxy-4,5-dimethyl-2-oxazolidinone (12d). Using the
general procedure with 0.55 g of 3e gave a mixture of
11d/12d (85:15), which after recrystallization (hexane/
CH2Cl2, 1:1) yielded 0.46 g (70%) of 11d as colorless
crystals: Rf 0.49 (hexane/EtOAc, 7:3); mp 76±778C, IR
(KBr) 3354, 1735, 1407, 1312, 1216, 1153, 1074,
1750, 1705, 1517, 1380, 1249, 1180, 1044, 981, 816 cm21
;
1H NMR (300 MHz, CDCl3) d 1.82 (br s, 3H, Me-6), 2.09
(br s, 3H, Me-7), 2.38 (s, 3H, CH3Ar), 7.12±7.28 (m, 4H,
ArH); 13C NMR (75.4 MHz, CDCl3) d 8.6 (C-6), 9.9 (C-7),
21.0 (C-12), 117.9 (C-4), 126.7 (C-9), 130.0 (C-10), 131.4
(C-8), 132.0 (C-5), 138.2 (C-11), 154.7 (C-2); MS (70 eV)
203 (M1, 40), 132 (100), 91 (28), 65 (18). Anal. Calcd for
C12H13NO2: C, 70.91; H, 6.45; N, 6.89. Found: C, 71.13; H,
6.51; N, 6.86.
;
1021 cm21 1H NMR (300 MHz, CDCl3) d 1.42 (d,
Jˆ6.6 Hz, 3H, Me-7), 1.48 (s, 3H, Me-6), 3.45±3.62 (m,
2H, H-8 or H-9), 3.63±3.76 (m, 2H, H-9 or H-8), 4.35 (q,
Jˆ6.6 Hz, 1H, H-5), 4.42 (br s, 1H, OH). Signals attributed
to minor isomer 12d: 1.33 (d, Jˆ6.6 Hz, Me-7), 1.48 (s,
Me-6), 4.50 (q, Jˆ6.6 Hz, H-5), 4.70 (br s, OH); 13C
NMR (75.4 MHz, CDCl3) d 12.7 (C-7), 23.5 (C-6), 41.1
(C-8 or C-9), 42.0 (C-9 or C-8), 80.5 (C-5), 87.9 (C-4),
158.0 (C-2); MS (70 eV) 193 (M1, 2), 178 (19), 144 (14),
121 (12), 106 (4), 86 (3), 72 (47), 43 (100). Anal Calcd for
C7H12ClNO3: C, 43.42; H, 6.25; N, 7.23. Found: C, 43.16;
H, 6.41; N, 7.50.
N-(2-Chloroethyl)-4,5-dimethyl-4-oxazolin-2-one (10d).
Using the general procedure with 0.28 g of 11d/12d
(85:15) gave 0.25 g (98%) of 10d as colorless crystals
(hexane/CH2Cl2, 3:7): Rf 0.56 (hexane/EtOAc, 7:3); mp
83±848C, IR (KBr) 1754, 1708, 1528, 1436, 1380, 1231,
1190, 1123 cm21; 1H NMR (300 MHz, CDCl3) d 1.90 (br s,
3H, Me-6), 1.94 (br s, 3H, Me-7), 3.62±3.67 (m, 2H, H-8 or
H-9), 3.69±3.74 (m, 2H, H-9 or H-8); 13C NMR (75.4 MHz,
CDCl3) d 7.9 (C-6 or C-7), 9.7 (C-7 or C-6), 41.1 (C-8), 43.2
(C-9), 117.3 (C-4), 131.5 (C-5), 155.2 (C-2); MS (70 eV)
177 (M112, 11), 175 (M1, 35), 140 (100), 114 (15), 82
(47), 68 (48). Anal. Calcd for C7H10ClNO2: C, 47.88; H,
5.74; N, 7.98. Found: C, 47.95; H, 5.53; N, 7.84.
General procedure for the preparation of N-substituted
4,5-dimethyl-4-oxazolin-2-ones 10a±10e
N-( p-Anisyl)-4,5-dimethyl-4-oxazolin-2-one (10e). To a
solution of 0.320 g (1.45 mmol) of 9d in dry ethyl ether
(15 mL) a drop of conc. H2SO4 was added. The mixture
was stirred at room temperature for 15 h, diluted with
ethyl ether (30 mL), and washed with an aqueous saturated
solution of NaHCO3 until neutral. The organic layer was
dried (Na2SO4), and the solvent was removed under
vacuum. The residue was recrystallized (hexane/CH2Cl2,
1:1) to give 0.31 (98%) of 10e as a white solid: Rf 0.40
(hexane/EtOAc, 7:3); mp 76±778C, IR (KBr) 1749, 1702,
A solution of alcohols 11/12 (1.4 mmol) in dry DMSO
(5 mL) was heated to re¯ux for 8 h. The solvent was
removed under vacuum, and the residue was puri®ed by
column chromatography on silica gel (30 g per gram of
crude) (hexane/EtOAc, 8:2).
4,5-Dimethyl-N-phenyl-4-oxazolin-2-one (10a). Using the
general procedure with 0.30 g of 11a/12a (76:24) gave
0.25 g (90%) of 10a as colorless crystals (hexane/CH2Cl2,
3:7): Rf 0.60 (hexane/EtOAc, 7:3); mp 79±808C [lit.21 79.5±
80.08C], IR (KBr) 1761, 1708, 1502, 1379, 1250,
1
1513, 1329, 1246, 1164, 1031, 979, 831 cm21; H NMR
1
1187 cm21; H NMR (300 MHz, CDCl3) d 1.85 (br s, 3H,
(300 MHz, CDCl3) d 1.81 (br s, 3H, Me-6), 2.10 (br s,
3H, Me-7), 3.83 (s, 3H, MeOAr), 6.94±7.00 (m, 2H,
ArH), 7.17±7.23 (m, 2H, ArH); 13C NMR (75.4 MHz,
CDCl3) d 8.9 (C-6), 10.1 (C-7), 55.6 (MeO), 114.8
(C-10), 118.3 (C-4), 127.0 (C-8), 128.4 (C-9), 131.9
Me-6), 2.11 (br s, 3H, Me-7), 7.23±7.48 (m, 5H, PhH); 13C
NMR (75.4 MHz, CDCl3) d 8.8 (C-6), 10.0 (C-7), 117.8
(C-4), 129.9 (C-9), 128.2 (C-11), 129.4 (C-10), 132.3
(C-5), 133.9 (C-8), 153.8 (C-2); MS (70 eV) 189 (M1,

Â
R. Martõnez et al. / Tetrahedron 56 (2000) 3857±3866
3865
(C-5), 154.2 (C-2), 159.6 (C-11); MS (70 eV) 219 (M1, 50),
174 (4), 148 (100), 107 (8), 92 (11), 77 (18). Anal. Calcd for
C12H13NO3: C, 65.78; H, 5.98; N, 6.39. Found: C, 65.90; H,
6.03; N, 6.47.
Â
J. J. Org. Chem. 1997, 62, 4105. (b) Hernandez, R.; Sanchez, J. M.;
Â
Gomez, A.; Trujillo, G.; Aboytes, R.; Zepeda, G.; Bates, R. W.;
Tamariz, J. Heterocycles 1993, 36, 1951.
Â
2. Boyd, G. V. In Comprehensive Heterocyclic Chemistry,
Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: Oxford,
1984; Vol. 6, pp 177±233.
5-Methyl-4-methylene-5-(3-oxobut-1-yl)-N-phenyl-2-oxa-
zolidinone (15). In a screw-cap ACE pressure tube, under
an N2 atmosphere, a mixture of 0.47 g (2.5 mmol) of 10a,
and 0.35 g (5.0 mmol) of 13 in dry xylene (3 mL) was
heated to 1508C for 24 h. The solvent was removed under
vacuum, and the residue was puri®ed by column chromato-
graphy on silica gel (30 g, hexane/EtOAc, 9:1) to give
0.53 g (83%) of 15 as colorless crystals (hexane/CH2Cl2,
1:1): Rf 0.50 (hexane/EtOAc, 7:3); mp 94±968C, IR (KBr)
3. (a) Guziec, F. S., Jr.; Tewes, E. T. J. Heterocyclic Chem. 1980,
17, 1807. (b) Sheehan, J. C.; Guziec Jr., F. S. J. Org. Chem. 1973,
38, 3034.
4. Kudo, N.; Taniguchi, M.; Furuta, S.; Sato, K.; Endo, T.; Honma,
T. J. Agric. Food Chem. 1998, 46, 5305.
5. (a) Gompper, R. Chem. Ber. 1956, 89, 1748. (b) Gompper, R.;
Herlinger, H. Chem. Ber. 1956, 89, 2816. (c) Gompper, R.;
Herlinger, H. Chem. Ber. 1956, 89, 2825. (d) deStevens, G.
1
1766, 1713, 1672, 1655, 1496, 1396, 1067 cm21; H NMR
È
J. Org. Chem. 1958, 23, 1572. (e) Gagneux, A. R.; Goschke, R.
Tetrahedron Lett. 1966, 45, 5451. (f) Lemmens, J. M.; Blommerde,
W. W. J. M.; Thijs, L.; Zwanenburg, B. J. Org. Chem. 1984, 49,
2231. (g) Sato, K.; Kinoto, T.; Sugai, S. Chem. Pharm. Bull. 1986,
34, 1553. (h) Hoffman, R. V.; Johnson, M. C.; Okonya, J. F.
Tetrahedron Lett. 1998, 39, 1283. (i) Vigroux, A.; Bergon, M.;
Zedde, C. J. Med. Chem. 1995, 38, 3983. (j) Shimizu, M.;
Yoshioka, H. J. Chem. Soc., Chem. Commun. 1987, 689. (k) Le
(300 MHz, CDCl3) d 1.62 (s, 3H, Me), 2.03±2.25 (m, 2H,
CH2), 2.19 (s, 3H, CH3CO), 2.48±2.74 (m, 2H, CH2CO),
4.05 (d, Jˆ3.0 Hz, 1H, H-6b), 4.20 (d, Jˆ3.0 Hz, 1H, H-6a),
7.28±7.52 (m, 5H, PhH); 13C NMR (75.4 MHz, CDCl3) d
27.0 (Me), 30.1 (CH3CO), 34.2 (CH2), 37.4 (CH2CO), 82.1
(CH2v), 83.0 (C-5), 127.0, 128.5, 129.7, 133.8, 149.8
(C-4), 154.5 (C-2), 207.2 (CO); MS (70 eV) 259 (M1, 1),
149 (19), 134 (20), 106 (43), 78 (61), 52 (100). Anal. Calcd
for C15H17NO3: C, 69.48; H, 6.61; N, 5.40. Found: C, 69.59;
H, 6.74; N, 5.43.
 Ã
Grende, P.; Jerome, F.; Bruneau, C.; Dixneuf, P. H. Chem.
Commun. 1998, 533.
6. Kimura, M.; Kure, S.; Yoshida, Z.; Tanaka, S.; Fugami, K.;
Tamaru, Y. Tetrahedron Lett. 1990, 31, 4887.
7. (a) Shapiro, S. L.; Bandurco, V.; Freedman, L. J. Org. Chem.
1961, 26, 3710. (b) Sisido, K.; Hukuoka, K.; Tuda, M.; Nozaki, H.
J. Org. Chem. 1962, 27, 2663. (c) Tamaru, Y.; Kimura, M.;
Tanaka, S.; Kure, S.; Yoshida, Z.-i. Bull. Chem. Soc. Jpn 1994,
67, 2838. (d) Shachat, N.; Bagnell Jr., J. J. J. Org. Chem. 1963, 28,
991. (e) Francis, T.; Thorne, M. P. Can. J. Chem. 1976, 54, 24. (f)
Stoffel, P. J.; Dixon, W. D. J. Org. Chem. 1964, 29, 978.
8. Marques, C. A.; Selva, M.; Tundo, P.; Montanari, F. J. Org.
Chem. 1993, 58, 5765.
2,5-Dimethyl-1-( p-nitrobenzoyloxy)-4-phenylamino-
benzene (18). 2-Acetyl-6-methyl-5-( p-nitrobenzoyloxy)-
4H-pyran (19).15 In a screw-cap ACE pressure tube,
under an N2 atmosphere, a mixture of 0.47 g (2.5 mmol)
of 10a, and 1.17 g (5.0 mmol) of 17 in dry xylene (3 mL)
was heated to 1808C for 24 h. The solvent was removed
under vacuum, and the residue was puri®ed by column chro-
matography on silica gel (30 g, hexane/EtOAc, 8:2) to give
0.41 g (45%) of 18 as a red powder (hexane/CH2Cl2, 1:1), Rf
0.70 (hexane/EtOAc, 7:3); and 0.23 g (61%) of 19 as a white
powder, Rf 0.75 (hexane/EtOAc, 7:3). Data of 18: mp 120±
1218C, IR (KBr) 3389, 1737, 1596, 1525, 1496, 1343, 1261,
9. (a) Mitsudo, T.-a.; Hori, Y.; Yamakawa, Y.; Watanabe, Y.
Tetrahedron Lett. 1987, 28, 4417. (b) Costa, D.; Chiusoli, G. P.;
Taffurelli, D.; Dalmonego, G. J. Chem. Soc., Perkin Trans. 1 1998,
1541.
1
1179, 1096 cm21; H NMR (300 MHz, CDCl3) d 2.14 (s,
3H, MeAr), 2.24 (s, 3H, MeAr), 4.20 (br s, 1H, NH), 6.89±
6.97 (m, 3H, PhH), 6.99 (br s, 1H, ArH), 7.14 (br s, 1H,
ArH), 7.24±7.30 (m, 2H, PhH), 8.37±8.39 (m, 4H, ArH);
13C NMR (75.4 MHz, CDCl3) d 16.1 (MeAr), 17.6 (MeAr),
117.5, 120.6, 121.4, 123.7, 123.8, 126.9, 128.0, 129.4,
131.3, 135.0, 139.5, 143.6, 144.0, 150.9, 163.5 (CO2).
Anal. Calcd for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73.
Found: C, 69.59; H, 4.76; N, 7.60.
10. Dxiomko, V. M.; Ivashchenko, A. V. Zh. Org. Khim. 1973, 9,
2191. Chem. Abstr. 1974, 80, 27154s.
11. Easton, N. R.; Cassady, D. R.; Dillard, R. D. J. Org. Chem.
1962, 27, 2927.
12. Traynelis, V. J.; Hergenrother, W. L.; Hanson, H. T.;
Valicenti, J. A. J. Org. Chem. 1964, 29, 123.
13. Reyes, A.; Aguilar, R.; Munoz, A. H.; Zwick, J.-C.; Rubio, M.;
Escobar, J.-L.; Soriano, M.; Toscano, R.; Tamariz, J. J. Org. Chem.
1990, 55, 1024.
Ä
14. Nagarajan, A.; Zepeda, G.; Tamariz, J. Tetrahedron Lett.
1996, 38, 6835.
Acknowledgements
15. Dudones, J. D.; Sampson, P. J. Org. Chem. 1997, 62, 7508.
16. Shantare, D.; Gudriniece, E.; Yure, M. Chem. Heterocycl.
Comp. 1999, 35, 146.
We thank Fernando Labarrios for his help in spectrometric
measurements. J. T. acknowledges DEPI/IPN (Grant
916510) and CONACYT (Grant 32273E) for ®nancial
support. R. M. thanks DEPI/IPN for a graduate fellowship
awarded, and the Ludwig K. Hellweg Foundation for a
scholarship complement.
Â
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17. Jimenez-Vazquez, H. A.; Ochoa, M. E.; Zepeda, G.; Modelli,
A.; Jones, D.; Mendoza, J. A.; Tamariz, J. J. Phys. Chem. A 1997,
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J. Am. Chem. Soc. 1985, 107, 3902.
19. RHF/3-21G calculations were performed using MacSpartan,19a
and at the 6-31Gp level with gaussian 94.19b (a) MacSpartan, v 1.0,
Wave Function Inc., 18401 Von Karman, Suite 370, Irvine, CA
92715. (b) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M.
W.; Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.;
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20. The atomic coordinates for these structures are available on
request from the Director of the Cambridge Crystallographic Data
Centre, University Chemical Laboratory, Lens®eld Road,
Cambridge, CB2 1EW. Any request should be accompanied by
the full literature citation for this communication.
21. Aversa, M. C.; Cum, G.; Giannetto, P. D.; Romeo, G.; Uccella,
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