Stereoselective electrogeneration of (E)-4-alkoxy-2-phenyl-5-chloro-2- oxazolines by cathodic reduction of N-(1-alkoxy-2,2,2-trichloroethyl)benzamides

Article abstract of DOI:10.1016/j.tet.2003.11.033

The first method for the synthesis of the title compounds has been established. Quantitative reactions of benzamides with chloral hydrate provided chloralbenzamides which were efficiently converted to N-(1,2,2,2- tetrachloroethyl)amides by treatment with

Full text of DOI:10.1016/j.tet.2003.11.033

Tetrahedron 60 (2004) 987–991
Stereoselective electrogeneration of
(E)-4-alkoxy-2-phenyl-5-chloro-2-oxazolines by cathodic
reduction of N-(1-alkoxy-2,2,2-trichloroethyl)benzamides
a
a
b
Antonio Guirado,a Raquel Andreu, Bruno Martiz and Jesus Galvez
,
*
´
´
a
´ ´ ´
Departamento de Quımica Organica, Facultad de Quımica, Universidad de Murcia, Campus de Espinardo, 30071 Murcia,
Apartado 4021, Spain
´ ´
Departamento de Quımica Fısica, Facultad de Quımica, Universidad de Murcia, Campus de Espinardo, 30071 Murcia,
b
´
Apartado 4021, Spain
Received 11 July 2003; revised 13 October 2003; accepted 12 November 2003
Abstract—The first method for the synthesis of the title compounds has been established. Quantitative reactions of benzamides with chloral
hydrate provided chloralbenzamides which were efficiently converted to N-(1,2,2,2-tetrachloroethyl)amides by treatment with phosphorus
pentachloride. These compounds reacted selectively with alcohols under mild conditions to give N-(1-alkoxy-2,2,2-trichloroethyl)benza-
mides in high yields which were stereoselectively transformed to (E)-4-alkoxy-2-aryl-5-chloro-2-oxazolines in fair to good yields by
electrochemical reduction under constant cathodic potential in an aprotic medium.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
research on the chemistry of these substances. Conse-
quently, the synthesis of different classes of 2-oxazolines
has received intense attention for many years. A recent
upsurge in interest has also been observed.7
We have recently developed a new heterocyclization
methodology based on the cathodic reduction of chloral
derivatives. Chloral is an inexpensive, commercially
available reagent whose versatile reactivity1 allows the
synthesis of a wide variety of cathodically active poly-
chlorinated derivatives. Some of these compounds seem
especially attractive for use as starting materials in
electroorganic synthesis, particularly those that have a
structural arrangement suitable to undergo a reductive
electrochemical heterocyclization process. The key step of
this type of transformation involves a migration of charge
on the first electrogenerated chlorocarbanion intermediate
to a remote heteroatom. In this way, the newly formed
anionic intermediate contains two suitably placed centres
with opposite nucleophilic–electrophilic activity capable of
promoting a ring closure process by internal displacement of
a chloride anion. This synthetic strategy was successfully
applied for preparing previously unknown 4-amino-2-aryl-
2-oxazolines2,3 which gave access to novel 2-imidazolidi-
nones, 1,3-oxazolidines and 1,3-thiazolidines.4 2-Oxa-
zolines are in general compounds of great interest5 since
they are versatile synthetic intermediates.5e–g Moreover,
their therapeutic potential5c,6 and many other significant
applications5c are also important factors in stimulating the
Given the high potentiality of this electrochemical
methodology for expanding the classes of 2-oxazolines
available, we attempted the synthesis of the hitherto
unknown 4-alkoxy-5-chloro-2-phenyl-2-oxazolines, as is
shown in Scheme 1.
2. Results and discussion
Chloralamides 2 were prepared8 in almost quantitative
yields by reaction of chloral hydrate with benzamides 1. In
order to prepare N-(1-alkoxy-2,2,2-trichloroethyl)benza-
mides 4 compounds 2 were firstly converted to N-(1,2,2,2-
tetrachloroethyl)benzamides 3 in high yields by reaction
with phosphorus pentachloride, as described previously.8b,9
It was found that products 3 undergo selective mono-
alkoxylation by simple treatment with a mixture of the
corresponding alcohol and triethyl amine in a 1:1 ratio to
give the targeted intermediates 4 in good to quantitative
yields.
Cathodic reductions of compounds 4 in an aprotic medium
Keywords: Benzamides; Oxazolines; Electrosynthesis; Reduction.
*
(acetonitrile–tetrabutylammonium perchlorate) at
mercury pool cathode were carried out under a constant
a
Corresponding author. Tel.: þ34-968367490; fax: þ34-968364148;
e-mail address: anguir@um.es
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.11.033

988
A. Guirado et al. / Tetrahedron 60 (2004) 987–991
Scheme 1.
potential of 21.50 V vs SCE. The electricity consumption
was 2 F/mol of 4 in all cases. After electrolyses, the
catholyte solutions were checked by TLC and GC, showing
a total transformation of starting materials to single
products, which were easily isolated and purified. These
were oily compounds that were identified by IR, MS, NMR
spectroscopy and elemental analysis as (E)-4-alkoxy-2-aryl-
5-chloro-2-oxazolines 5 which pertain to a new family of
2-oxazoline compounds. Yields ranged from fair to good.
The results of the cathodic reductions of N-(1-alkoxy-2,2,2-
trichloroethyl)benzamides 4, along with our previous
reports2,3 on studying electroreductions of N-(1-amino-
2,2-dichloroethyl)benzamides, provide important insights
into the high potential of this heterocyclization method-
ology, which appears specially suitable to accomplish the
synthesis of complex 2-oxazolines.
The formation of oxazolines 5 (Scheme 2) can be
reasonably explained on the basis of a two-electron selective
cathodic cleavage of one carbon–chlorine bond with
generation of a dichlorocarbanionic intermediate which
would generate an amide anion. Therefore, the cyclization
to yield racemic products 5 would occur by nucleophilic
displacement of one of the remaining chlorine atoms. A
transition state involving minimal steric interactions
between the stationary chlorine atom and a vicinal alkoxyl
group would participate.
Spectroscopic analyses of products 5 were corroborated by
treatment of 5b with potassium tert-butoxide. It caused a
total conversion to 2-phenyl-4-methoxyoxazol 6b, which
was conclusively identified by comparison with an authentic
sample.10
On the other hand, it was found that electrogeneration of
products 5 occurs with stereoselectivity towards the
formation of (E)-isomers. This configurational assignment
1
is firmly supported by categorical H NMR studies11,12 on
Given the success in preparing the oxazolines 5, we also
attempted the synthesis of 4-alkoxy-2-phenyl-2-oxazolines
8 by applying a similar methodology. N-(1-Ethoxy-2,2-
trichloroethyl)benzamide 7a was used as model compound
for this study. It was prepared by cathodic reduction of 4a in
a protic medium. The electrochemical reduction of 7a was
carried out under a similar experimental conditions to those
used in the electrolyses of compounds 4. A considerably
more negative potential (21.90 V versus SCE), however,
must be applied in this case. In contrast to that observed
with compounds 4, the passing current did not decrease
spontaneously whenthechargeconsumptionreached2 F/mol.
stereochemistry of substituted five-membered cyclic com-
pounds from which it has been established as a general rule
that the arrangement of vicinal protons corresponds to a (E)-
configuration when they show spin coupling constants of
J,5 Hz, whereas a (Z)-configuration always shows coup-
ling constants with J.5 Hz, and ,8 Hz is the value most
frequently found. This method leads to the conclusion that
the stereochemistry of products 5 corresponds to a (E)-
configuration since the coupling constants between H-4 and
H-5 protons are remarkably small, with J values ranging
from 1.5 to 1.6 Hz in all cases.

A. Guirado et al. / Tetrahedron 60 (2004) 987–991
989
Scheme 2.
At values close to 3 F/mol, the catholyte showed a high
basicity; the electrolysis was then stopped and the reaction
products present in the catholyte were analyzed by GC/MS. A
complex mixture of compounds with 2-phenyloxazol 9 (24%)
and 4-ethoxy-2-penyl-2-oxazoline 8a (17%) as main com-
ponents was detected. The identity of 9 was corroborated by
comparison with an authentic specimen.13 The progressive
conversion of 8a to 9 in the basic catholyte medium was
observed, and even occurred without electricity passing. In the
case of shorter electrolyses (1.9 F/mol), a remarkable variety
of reaction products was also observed. These adverse results
are attributable to the highly negative cathodic potential
operating, which causes indiscrimination in electrode process
and basicity in the solvent–electrolyte system.
3.2. Preparation of N-(1-alkoxy-2,2,2-trichloroethyl)-
benzamides (4)
General procedure. A solution of the corresponding alcohol
(5.25 mmol) and triethylamine (5.25 mmol) in dry acetone
(6 mL) was added dropwise at room temperature to a stirred
solution of the appropriate N-(1,2,2,2-tetrachloroethyl)-
amide 3 (5.25 mmol) in dry acetone (9 mL) and the stirring
was continued for 10 h. The white solid precipitate formed
was removed by filtration and the solvent was evaporated
under reduced pressure leaving a residue which was washed
with cold petroleum ether. The resulting solid product was
crystallized in the appropriate solvent.
Preparation of 4a. N-(1,2,2,2-Tetrachloroethyl)benzamide
3a (7 mmol) was added to dry ethanol (30 mL) and the
stirred solution was heated at 40 8C for 1 h. After cooling
the crystalline product was isolated by filtration.
To conclude, a convenient method for the synthesis of (E)-
a
4-alkoxy-2-aryl-5-chloro-2-oxazolines,
previously
unattainable class of compounds, is reported. Versatility,
good yields, easy availability of starting materials, mildness
and simple experimental procedure are noteworthy
advantages of this approach. However, this method has
been found to be of no use in the synthesis of 4-alkoxy-2-
aryl-2-oxazolines.
3.2.1. N-(2,2,2-Trichloro-1-ethoxyethyl)benzamide (4a).
96%. Colourless needles, mp 148 8C (ethanol). (Found: C,
44.64; H, 4.14; N, 4.77. C11H12Cl3NO2 requires: C, 44.55;
1
H, 4.08; N, 4.72); H NMR d (CDCl3, 200 MHz): 1.31 (t,
3H, J¼7.2 Hz), 3.79–3.94 (m, 2H), 5.90 (d, 1H, J¼9.8 Hz),
6.75 (d, 1H, J¼9.8 Hz), 7.26–7.58 (m, 3H), 7.81–7.86 (m,
2H); 13C NMR d (CDCl3, 50.4 MHz): 14.91 (CH3), 66.54
(CH2), 86.39 (CH), 99.66 (CCl3), 127.28 (CH), 128.94 (CH),
132.61 (CH), 133.05(C), 167.46(CO); MS, m/z (%): 216 (29),
178 (17), 105 (100), 77 (91), 51 (36); IR (Nujol): 3306, 1645,
3. Experimental
3.1. General
1516, 1462, 1340, 1272, 1108, 915, 821, 791, 720 cm21
.
NMR spectra were determined on Bruker AC-200 or Varian
Unity 300 Unity instruments with tetramethylsilane as
internal reference. Electron-impact mass spectra were
obtained on Hewlett–Packard 5995 and Autospect 5000
VG spectrometers under an ionizing voltage of 70 eV. IR
spectra (nujol emulsions) were recorded on a Nicolet Impact
400 spectrophotometer. Microanalyses were performed on a
Carlo Erba EA-1108 analyzer. Melting points were
determined on a Kofler hot-plate melting point apparatus,
and are uncorrected. Electrochemical experiments were
performed with an Amel 557 potentiostat coupled to an
Amel 558 integrator. Chloralamides 2 and N-(1,2,2,2-
tetrachloroethyl)benzamides 3 were prepared as described
previously.8b,9
3.2.2. N-(2,2,2-Trichloro-1-methoxyethyl)benzamide
(4b). 98%. Colourless needles, mp 99–102 8C (pet ether).
(Found: C, 42.48; H, 3.62; N, 5.01. C10H10Cl3NO2 requires:
C, 42.51; H, 3.57; N, 4.96); 1H NMR d (CDCl3, 200 MHz):
3.63 (s, 3H), 5.82 (d, 1H, J¼10.0 Hz), 6.75 (d, 1H,
J¼10.0 Hz), 7.45–7.59 (m, 3H), 7.82–7.87 (m, 2H); 13C
NMR d (CDCl3, 50.4 MHz): 58.01 (CH3), 87.89 (CH),
99.22 (CCl3), 127.29 (CH), 128.95 (CH), 132.69 (CH),
132.85 (C), 167.71 (CO); MS, m/z (%): 283 (Mþþ2, 4), 281
(Mþ, 5), 246 (11), 215 (51), 164 (82), 126 (21), 105 (100),
77 (89); IR (Nujol): 3266, 1648, 1523, 1461, 1377, 1103,
796 cm21
.

990
A. Guirado et al. / Tetrahedron 60 (2004) 987–991
3.2.3. N-[2,2,2-Trichloro-1-(2-phenylethoxy)ethyl]ben-
zamide (4c). 65%. Colourless needles, mp 97 8C (pet
ether). (Found: C, 54.89; H, 4.29; N, 3.71. C17H16Cl3NO2
electrolysis products were isolated by removing the solvent
in vacuo. The residue was then shaken with ether
(3£50 mL) over a period of 30 min. The ethereal solutions
were combined and concentrated leaving oily crude
products that were purified by column chromatography on
silica gel (entries a, b, d, e: ethyl acetate or ethyl acetate–
hexane 1:3; entry c: petroleum ether–diethyl ether 4:1). The
isolated products were viscous oils that gave satisfactory
elemental and spectroscopic analyses.
1
requires: C, 54.79; H, 4.33; N, 3.76); H NMR d (CDCl3,
200 MHz): 2.96 (t, 2H, J¼6.9 Hz), 3.95–4.05 (m, 2H), 5.90
(d, 1H, J¼9.8 Hz), 6.53 (d, 1H, J¼9.8 Hz), 7.23–7.25 (m,
5H), 7.42–7.57 (m, 3H), 7.68–7.73 (m, 2H); 13C NMR d
(CDCl3, 50.4 MHz): 35.97 (CH2), 71.33 (CH2), 86.53 (CH),
99.45 (CCl3), 126.51 (CH), 127.28 (CH), 128.44 (CH),
128.87 (CH), 129.18 (CH), 132.61 (C), 132.89 (CH), 138.12
(C), 167.49 (CO); MS, m/z (%): 371 (Mþ0.2), 336 (0.4), 250
(2), 216 (8), 105 (100), 91 (25), 77 (93); IR (Nujol): 3285,
3.3.1. (E)-5-Chloro-4-ethoxy-2-phenyl-2-oxazoline (5a).
65%. Pale yellow oil. (Found: C 58.40; H 5.41; N 6.18;
C11H12ClNO2 requires C 58.55; H 5.36; N 6.21); 1H NMR d
(CDCl3, 300 MHz): 1.27 (t, 3H, J¼7.2 Hz), 3.71–3.77 (m,
1H), 3.93–3.98 (m, 1H), 5.61 (d, 1H, J¼1.5 Hz), 6.16 (d,
1H, J¼1.5 Hz), 7.44–7.60 (m, 3H), 8.06–8.08 (m, 2H); 13C
NMR d (CDCl3, 75.4 MHz): 15.23 (CH3), 64.91 (CH2),
92.44 (CH), 104.91 (CH), 125.77 (C), 128.71 (CH), 129.33
(CH), 133.17 (CH), 165.92 (CvN); MS, m/z (%): 225 (Mþ,
3), 190 (4), 180 (8), 161 (58), 152 (10), 132 (10), 117 (25),
104 (100), 90 (14), 77 (51), 51 (30); IR (film): 2982, 2933,
1656, 1449, 1337, 1252, 1103, 1032, 979, 895, 749,
1648, 1528, 1464, 1379, 1277, 1098, 1081, 813, 699 cm21
.
3.2.4. N-[2,2,2-Trichloro-1-(3,4,5-trimethoxybenzyl-
oxy)ethyl]benzamide (4d). 75%. Colourless needles, mp
102–103 8C (dichloromethane–hexane). (Found: C, 50.66;
H, 5.08; N, 3.26. C19H20Cl3NO5 requires: C, 50.86; H, 4.49;
N, 3.12); 1H NMR d (CDCl3, 300 MHz): 3.79 (s, 3H), 3.81
(s, 6H), 4.75 (s, 2H), 6.00 (d, 1H, J¼9.6 Hz), 6.64 (s, 2H),
6.75 (d, 1H, J¼9.6 Hz), 7.44–7.58 (m, 3H), 7.77 (d, 2H,
J¼6.0 Hz); 13C NMR d (CDCl3, 75.4 MHz): 56.02 (CH3O),
60.75 (CH3O), 72.31 (CH2), 85.80 (CH), 99.38 (CCl3),
105.36 (CH), 127.15 (CH), 128.83 (CH), 131.69 (C), 132.61
(CH), 132.74 (C), 137.83 (C), 153.20 (C), 167.37 (CO); MS,
m/z (%): 447 (Mþ, 27), 216 (100), 196 (36), 181 (34), 169
(30), 148 (18), 138 (21), 105 (34), 77 (75); IR (Nujol): 3276,
1681, 1597, 1530, 1465, 1379, 1332, 1270, 1239, 1133,
693 cm21
.
3.3.2. (E)-5-Chloro-2-phenyl-4-methoxy-2-oxazoline
(5b). 79%. Pale yellow oil. (Found: C 56.80; H 4.70; N
1
6.56; C10H10ClNO2 requires C 56.75; H 4.76; N 6.62); H
NMR d (CDCl3, 200 MHz): 3.55 (s, 3H), 5.52 (d, 1H,
J¼1.6 Hz), 6.14 (d, 1H, J¼1.6 Hz), 7.40–7.55 (m, 3H),
8.00–8.06 (m, 2H); 13C NMR d (CDCl3, 50.4 MHz): 56.19
(CH3O), 91.96 (CH), 106.51 (CH), 126.01 (C), 128.57
(CH), 129.06 (CH), 132.83 (CH), 165.67 (CvN); MS, m/z
(%): 211 (Mþ, 4), 176 (8), 147 (75), 117 (11), 104 (100), 90
(10), 77 (39); IR (film): 2942, 2836, 1659, 1651, 1452, 1337,
1085, 1011, 815, 697 cm21
.
3.2.5. N-[2,2,2-Trichloro-1-(4-methoxybenzyloxy)ethyl]-
benzamide (4e). 73%. Colourless needles, mp 105–107 8C
(hexane). (Found: C, 52.60; H, 4.09; N, 3.52.
1
C17H16Cl3NO3 requires: C, 52.53; H, 4.15; N, 3.60); H
NMR d (CDCl3, 200 MHz): 3.78 (s, 3H), 4.76 (d, 2H,
J¼6.4 Hz), 5.95 (d, 1H, J¼9.8 Hz), 6.73 (d, 1H, J¼9.8 Hz),
6.87 (d, 2H, J¼8.6 Hz), 7.34 (d, 2H, J¼8.6 Hz), 7.44–7.58
(m, 3H), 7.80 (dd, 2H, J¼6.7, 1.2 Hz); 13C NMR d (CDCl3,
50.4 MHz): 55.30 (CH3O), 71.93 (CH2), 85.57 (CH), 99.54
(CCl3), 113.98 (CH), 127.27 (CH), 128.17 (C), 128.90
(CH), 130.20 (CH), 132.60 (CH), 133.01 (C), 159.78 (C),
167.46 (CO); MS, m/z (%): 387 (Mþ, 2), 252 (2), 233 (3),
216 (74), 180 (10), 137 (58), 121 (78), 105 (100), 77 (62); IR
(Nujol): 3328, 1657, 1520, 1461, 1349, 1258, 1097, 1056,
1105, 1063, 1033, 981, 968, 849, 746 cm21
.
3.3.3. (E)-5-Chloro-2-phenyl-4-(2-phenylethoxy)-2-oxa-
zoline (5c). 82%. Pale yellow oil. (Found: C 67.77; H
5.35; N 4.60; C17H16ClNO2 requires C 67.66; H 5.34; N
4.64); 1H NMR d (CDCl3, 300 MHz): 2.95 (t, 2H,
J¼7.2 Hz), 3.85–3.90 (m, 1H), 4.05–4.10 (m, 1H), 5.59
(d, 1H, J¼1.5 Hz), 6.08 (d, 1H, J¼1.5 Hz), 7.21–7.47 (m,
8H), 8.00–8.04 (m, 2H); 13C NMR d (CDCl3, 75.4 MHz):
36.34 (CH2), 69.80 (CH2), 92.25 (CH), 105.82 (CH), 126.48
(CH), 128.52 (CH), 128.65 (CH), 129.00 (CH), 129.11
(CH), 132.81 (CH), 165.57 (CvN); MS, m/z (%): 301 (Mþ,
6), 266 (7), 197 (4), 180 (14), 152 (21), 104 (100), 91 (24),
77 (32); IR (film): 3029, 2925, 2870, 1725, 1660, 1498,
1034, 998, 808, 716 cm21
.
3.3. Preparation of (E)-4-alkoxy-5-chloro-2-phenyl-2-
oxazolines (5)
1453, 1253, 1099, 1031, 972, 750, 701 cm21
.
Preparative electrolyses were carried out under a constant
cathodic potential in a concentric cylindrical cell with two
compartments separated by a circular glass frit (medium)
diaphragm. A mercury pool (diameter 5 cm) was used as the
cathode and a platinum plate as the anode. The catholyte
was magnetically stirred. The temperature was kept at
approximately 18 8C by external cooling. The reductions
were performed in anhydrous MeCN–Bu4NClO4, 0.4 M, of
which approximately 35 mL and 15 mL were placed,
respectively, in the cathodic and the anodic compartments.
Anhydrous sodium carbonate (3 g) was placed in the anode
compartment to prevent accumulation of electrogenerated
acid. Solutions of compounds 4 (5 mmol) were electrolyzed
under a cathodic potential of 21.50 V vs SCE. All
3.3.4. (E)-5-Chloro-2-phenyl-4-(3,4,5-trimethoxybenzyl-
oxy)-2-oxazoline (5d). 66%. Pale yellow oil. (Found: C
60.29; H 5.40; N 3.63; C19H20ClNO5 requires C 60.40; H
5.34; N 3.71); 1H NMR d (CDCl3, 300 MHz): 3.64 (s, 3H),
3.66 (s, 6H), 4.46 (d, 1H, J¼11.7 Hz), 4.65 (d, 1H,
J¼11.7 Hz), 5.50 (d, 1H, J¼1.5 Hz), 5.99 (d, 1H,
J¼1.5 Hz), 6.42 (s, 2H), 7.23–7.36 (m, 3H), 7.85 (d, 2H,
J¼7.2 Hz); 13C NMR d (CDCl3, 75.4 MHz): 56.08 (CH3O),
60.81 (CH3O), 70.97 (CH2), 92.21 (CH), 105.13 (CH),
126.14 (CH), 128.60 (CH), 129.02 (CH), 130.37 (C), 132.57
(C), 132.83 (CH), 137.76 (C), 153.36 (C), 165.77 (CvN);
MS, m/z (%): 379 (Mþþ2, 23), 377 (Mþ, 35), 342 (7), 196
(40), 181 (100), 167 (14), 146 (42), 104 (34), 77 (29); IR

A. Guirado et al. / Tetrahedron 60 (2004) 987–991
991
(film): 2946, 1738, 1650, 1594, 1506, 1463, 1423, 1336,
1239, 1130, 1083, 1008, 848 cm21
Acknowledgements
We gratefully acknowledge the financial support of the
.
´
Ministerio de Ciencia y Tecnologıa (project BQU2000-
0222).
3.3.5. (E)-5-Chloro-2-phenyl-4-(4-methoxybenzyloxy)-2-
oxazoline (5e). 64%. Pale yellow oil. (Found: C 64.13; H
5.11; N 4.34; C17H16ClNO3 requires C 64.26; H 5.08; N
4.41); 1H NMR d (CDCl3, 200 MHz): 3.78 (s, 3H), 4.63 (d,
1H, J¼11.2 Hz), 4.84 (d, 1H, J¼11.2 Hz), 5.66 (d, 1H,
J¼1.5 Hz), 6.13 (d, 1H, J¼1.5 Hz), 6.88 (d, 2H, J¼8.6 Hz),
7.31 (d, 2H, J¼8.6 Hz), 7.44–7.55 (m, 3H), 8.03 (dd, 2H,
J¼8.0, 1.2 Hz); 13C NMR d (CDCl3, 50.4 MHz): 55.33
(CH3O), 70.49 (CH2), 92.38 (CH), 104.76 (CH), 114.02
(CH), 126.31 (C), 128.61 (CH), 129.09 (CH), 129.92
(CH), 132.77 (CH), 159.62 (C), 165.67 (CvN); MS, m/z
(%): 318 (Mþþ1, 2), 152 (8), 146 (100), 121 (67), 104 (31),
91 (15), 77 (35), 63 (9); IR (film): 2939, 1719, 1651, 1612,
1513, 1451, 1339, 1253, 1178, 1084, 1033, 971, 823,
References and notes
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´
´
1999, 40, 8163. (b) Guirado, A.; Andreu, R.; Galvez, J.
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750 cm21
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3.3.6. Preparation of N-(2,2-dichloro-1-ethoxyethyl)ben-
zamide (7a). Product 7a was electrochemically prepared by
cathodic reduction by using a divided cell as described
above. The electrolysis of compound 4a (3 mmol) was
carried out under a constant cathodic potential of 21.60 V
vs SCE in DMF–LiClO4 0.4 M. Acetic acid (3 mmol)
was used as proton donor. The electricity consumption was
2 F/mol. The electrolysis product was isolated by dropping
the catholyte solution onto ice–water (200 mL). The white
solid precipitated was air-dried and crystallized from
petroleum ether.
6. (a) Hansen, D. W.; Currie, M. G.; Hallinan, E. E. PCT. Int.
Appl. WO 95,11,231; CA 123, 111865. (b) Suter, W.; Jager, I.;
Racine, R. R.; Donastsch, F.; Neumann, P.; Matter, B. E.
Environ. Mutagen 1983, 5, 527. (c) Wong, W. C.; Wang, D.;
Forray, C. Bioorg. Med. Chem. Lett. 1994, 4, 2317.
80%. White needles, mp 98–99 8C (pet ether). (Found: C,
50.58; H, 4.93; N, 5.28. C11H13Cl2NO2 requires: C, 50.40;
7. See for example: (a) Zhou, P. W.; Blubaum, J. E.; Burns, C. T.;
Natale, N. R. Tetrahedron Lett. 1997, 38, 7019. (b) Lerestif,
J. M.; Toupet, L.; Sinbandhit, S.; Tonnard, F.; Bazureau, J. P.;
Hamelin, J. Tetrahedron 1997, 53, 6351. (c) Jnaneshwara,
G. K.; Deshpande, V. H.; Lalithambika, M.; Ravindranathan,
T.; Bedekar, A. V. Tetrahedron Lett. 1998, 39, 259.
(d) Kamata, K.; Agata, I.; Meyers, A. I. J. Org. Chem. 1998,
63, 3113. (e) Suga, H.; Ikai, K.; Ibata, T. J. Org. Chem. 1999,
64, 7040. (f) Ito, Y.; Higuchi, N.; Murakami, M. Heterocycles
2000, 52, 91.
1
H, 5.00; N, 5.34); H NMR d (CDCl3, 200 MHz): 1.26 (t,
3H, J¼7.0 Hz), 3.71–3.82 (m, 2H), 5.78 (dd, 1H, J¼9.5,
2.4 Hz), 5.89 (d, 1H, J¼2.4 Hz), 6.85 (d, 1H, J¼9.5 Hz),
7.44–7.57 (m, 3H), 7.84 (d, 2H, J¼6.8 Hz); 13C NMR d
(CDCl3, 50.4 MHz): 14.95 (CH3), 65.23 (CH2), 72.67
(CHCl2), 81.54 (CH), 127.24 (CH), 128.83 (CH), 132.42
(CH), 133.16 (C), 167.59 (CO); MS, m/z (%): 224 (4), 218
(14), 216 (22), 178 (11), 105 (100), 77 (58), 51 (18); IR
(Nujol): 3211, 1635, 1524, 1466, 1379, 1085, 791,
696 cm21
.
8. (a) Meldrum, A. N.; Bhojraj, M. G. J. Indian Chem. Soc. 1936,
´
13, 185. (b) Guirado, A.; Andreu, R.; Cerezo, A.; Galvez, J.
Tetrahedron 2001, 39, 4925.
3.3.7. Reductive electrolysis of N-(2,2-dichloro-1-ethoxy-
ethyl)benzamide (7a). Cathodic reductions of 7a were
performed in a divided cell as described above and were
carried out under a constant cathodic potential of 21.90 V
vs SCE in acetonitrile–tetrabutylammonium perchlorate
0.5 M. The electrolysis products were isolated by removing
the solvent in vacuo. The residue was then shaken with ether
(3£50 mL) over a period of 30 min. The ethereal solutions
were combined and concentrated. These experiments
revealed no synthetic utility since the formation of complex
mixtures of products was detected by GC/MS. For a 3 F/mol
electrolysis, 2-phenyloxazol 9 (24%) and 4-ethoxy-2-penyl-
2-oxazoline 8a (17%) could be identified among other non
characterised products.
9. Guirado, A.; Andreu, R.; Zapata, A.; Cerezo, A.; Bautista, D.
Tetrahedron 2002, 58, 5087.
10. (a) Scarpati, R.; Graziano, M. L.; Nicolaus, R. Gazz. Chim.
Ital. 1968, 98, 681. (b) Drach, B. S.; Sedlov, A. I.; Mis’kevich,
G. N. Zh. Org. Khim. 1978, 14, 1827.
11. Constantino, M. G.; Jose da Silva, G. V. Tetrahedron 1998, 54,
11363.
12. Gaudemer, A. Stereochemistry fundamentals and methods;
Kagan, H. B., Ed.; Georg Thieme: Stuttgart, 1977; Vol. 1, p 89.
13. (a) Padwa, A.; Rasmussen, J. K.; Temper, A. J. Am. Chem.
Soc. 1976, 98, 2605. (b) Belen’kii, L. I.; Bogolanov, V. S.;
Abronin, I. A.; Gromova, G. P.; Cheskis, M. A.; Zakharyan,
R. Z. Chem. Scripta 1985, 25, 266.