Stereoselective synthesis of (E)-4-alkoxy-2-aryl-5-chloro-2-thiazolines

Article abstract of DOI:10.1016/j.tet.2006.07.086

The first synthesis of the title compounds has been achieved starting from chloralamides by a route involving chemical and electrochemical steps. N-(1-Alkoxy-2,2,2-trichloroethyl)benzamides were efficiently prepared from chloralbenzamides and were electro

Full text of DOI:10.1016/j.tet.2006.07.086

Tetrahedron 62 (2006) 9688–9693
Stereoselective synthesis of (E)-4-alkoxy-2-aryl-5-chloro-
2-thiazolines
*
Antonio Guirado, Raquel Andreu, Bruno Martiz and Sergio Perez-Ballester
ꢀ
´
Departamento de Quımica Organica, Facultad de Quımica, Universidad de Murcia, Campus de Espinardo, 30071 Murcia,
ꢀ
´
Apartado 4021, Spain
Received 27 April 2006; revised 12 July 2006; accepted 25 July 2006
Available online 21 August 2006
Abstract—The first synthesis of the title compounds has been achieved starting from chloralamides by a route involving chemical and electro-
chemical steps. N-(1-Alkoxy-2,2,2-trichloroethyl)benzamides were efficiently prepared from chloralbenzamides and were electrochemically
converted into N-(1-alkoxy-2,2-dichloroethyl)benzamides in high yields by cathodic reduction in a protic medium. Thionation of these
compounds with Lawesson’s reagent followed by basic treatment gave novel (E)-4-alkoxy-2-aryl-5-chloro-2-thiazolines in fair to quantitative
yields.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Chloral is an inexpensive multipurpose starting material for
organic synthesis.23 We have recently developed a new
preparative methodology based on using chloral derivates
having a molecular arrangement suitable to undergo a direct
heterocyclization process that is promoted electrochemi-
cally. This method was successfully applied to prepare
new types of 2-oxazolines,23,24 which provided access to
novel 2-imidazolidinones,25 1,3-oxazolidines, and 1,3-thia-
zolidines.26 One of the most advantageous features of this
synthetic tactic lies in the synthesis of chlorinated oxazo-
lines, since severe problems of chemical incompatibility
with the usual chlorinating reagents can be avoided by using
certain prechlorinated synthons derived from chloral. Given
the previous success of our methodology on the synthesis of
2-oxazolines, and in order to expand the number of 2-thiazo-
line derivatives available, we recognized the opportunity to
attempt an approach to synthesis 5-chloro-2-thiazolines,
since these products pertain to a hitherto unknown family
of compounds, of interest by themselves, as well as for their
synthetic potential.
Thiazoline chemistry is receiving considerable attention
because of its occurrence in biologically active natural
products of interest such as curacin A,1 thiangazole,2 mirab-
azoles,3 apratoxins,4 etc. Furthermore, thiazolines are being
used as building blocks in pharmaceutical drug discovery.5,6
Some thiazoline derivates present interesting activity such as
anti-HIV,2a anti-cancer,7 antimitotic,1b,1c and antibiotic5c
agents. Therefore, new procedures for preparing these
compounds attract substantial research interest.
Over the years, a number of approaches to make these hetero-
cycles have been developed.8 The most commonly used
synthetic approaches to these compounds are based on cyclo-
dehydration of b-hydroxythioamides under the Mitsunobu
conditions,5a,9 the Burgess reagent [methylN-(triethylammo-
nium sulfonyl)carbamate],5a,9b [bis(2-methoxyethyl)amino]-
sulfur trifluoride,10 or diethylamidosulfur trifluoride.11
Condensations of 2-aminothiols with nitriles,12 carboxylic
acids,13 esters,14 iminoethers,15 or iminotriflates16 is also
exploitable reactions. Thiazolines have also been prepared
from acylamino and thioacylamino alcohols11,17,18 or by
multistepconversionsfromoxazolines.19Morerecentmethods
have been described, like ruthenium-catalyzed oxidation
of thiazolidine to thiazoline,20 reaction of aminothiols with
N-acylbenzotriazoles under microwave irradiation,21 or
annulation of thioamides with 2-alkynoates.22
With the aim of exploring the possibility of adaptation of our
earlier preparative strategy to this new objective, chloral-
amide 2a was transformed to trichloromethyl thioamide 8a
(Scheme 1, route A) by treatment with Lawesson’s re-
agent27,28 (LR). In contrast to what was expected on the basis
of our previous experiments on 2-oxazoline electrosyn-
thesis, a direct generation of the targeted (E)-5-chloro-4-
methoxy-2-thiazoline 7a by cathodic reduction of 8a was
not feasible. This process was found to be totally unselective,
probably due to equality in electroactivity at thiocarbonyl
and trichloromethyl centers. Fortunately, this adversity could
be overcome by carrying out an electroreduction–thionation
Keywords: Thiazolines; Chloralamides; Reduction; Thionation; Electro-
synthesis.
* Corresponding author. Tel.: +34 968367490; fax: +34 968364148; e-mail:
anguir@um.es
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.086

A. Guirado et al. / Tetrahedron 62 (2006) 9688–9693
9689
steps run (Scheme 1, route B), instead of the failed thiona-
tion–electroreduction reaction sequence.
electrosynthesis of 2-oxazolines23,24 was investigated (route
A). Thionation of compound 4a with LR gave 8a (72 %),
which was electrolyzed in an aprotic medium (ꢀ1.6 V vs
SCE) leading to a complex mixture of unidentified products
instead of the expected thiazoline 7a, due to an indiscrimi-
nate electrode process. In view of this difficulty it was
intended that an alternative reaction sequence like route
B would be able to provide the required compounds 7,
since the non-sulfurated intermediates 4 would be able to
undergo a more selective electrochemical reduction than
the sulfurated intermediates 8. Thus, cathodic reductions
of compounds 4 in a protic medium were carried out under
constant potential of ꢀ1.7 V vs SCE. The electricity
consumption was 2 F/mol of 4 in all cases. After electro-
lyses the reaction products were easily isolated in high
yields by simple mixing of the catholyte solution with
water and filtration. After crystallization highly pure white
compounds were isolated and identified by elemental
analysis and IR, MS, and NMR spectroscopy as inter-
mediates 5.
O
O
OH
O
O
Cl
Cl3CCHO
NH2
PCl5
CCl3
CCl3
Ar
Ar
Ar
NH
Ar
NH
3 (85-98%)
2 (92-95%)
1
ROH
OR
S
OR
2e, -2Cl–
LR
CCl3
CCl3
4 (65-97%)
NH
NH
8
Ar
A
2e, H+, -Cl–
OR
B
S
OR
O
OR
Cl
NaOH
N
LR
Ar
Ar
NH
NH
5 (70-98%)
CHCl2
CHCl2
Ar
6 (62-95%)
OH–
S
7 (74-96%)
N–
N
OR Ar
CHCl2
OR
Ar
Complete conversions of amides 5 into thioamides 6 were
achieved by treatment with Lawesson’s reagent on refluxing
toluene for 1 h and isolated by column chromatography,
resulting in yellow products in fair to high yields that were
identified and characterized by elemental analysis and IR,
MS, and NMR spectroscopy.
S–
CHCl2
S
9
H
OR
N
Ar
δ– -Cl–
δ–
7
S
Cl
H
Cl
Alkaline treatment of compounds 6 under mild temperature
conditions provided products in good to quantitative yields,
which were identified by the usual techniques as (E)-4-alk-
oxy-5-chloro-2-thiazolines 7. As far as we know, this is
the first time that compounds of this type have been synthe-
sized. They seem to have special interest due to a potential
capacity to be used as synthetic intermediates to prepare
many other heterocyclic derivatives.
Entry
R
Ar
a
b
C6H5
C6H5
C6H5
CH3
CH3CH2
c
d
e
C6H5CH2CH2
C6H5CH2CH2
C6H5CH2
4-ClC6H4
1H NMR spectroscopic analyses confirmed that trans-
formation of compounds 6 to products 7 occurs with total
stereoselectivity toward the formation of (E)-isomers. A
transition state between anionic species 9 and final products
7 involving minimal steric interactions between the station-
ary chlorine atom and a vicinal alkoxyl group explains the
stereochemical fate of this internal displacement process.
This configurational assignment is firmly supported by
categorical studies31 on stereochemistry of substituted
five-membered cyclic compounds, 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)-con-
figuration always shows coupling constants with J>5 Hz,
beingw8 Hz the value most frequently found. This method
clearly leads to the conclusion that the stereochemistry of
compounds 7 corresponds to a (E)-configuration, since the
coupling constant between H-4 and H-5 protons is remark-
ably small, with J values ranging from 1.0 to 1.2 Hz in
all cases.
4-MeC6H4
4-MeC6H4
2-ClC6H4
2-MeC6H4
f
4-MeOC6H5CH2
g
3,4,5-(MeO)3C6H2CH2
3,4,5-(MeO)3C6H2CH2
h
Scheme 1.
2. Results and discussion
Chloralamides 2 were prepared29 in almost quantitative
yields by reaction of chloral hydrate with benzamides 1
(Scheme 1). In order to prepare N-(1-alkoxy-2,2,2-trichloro-
ethyl)benzamides 4, compounds 2 were firstly converted
into N-(1,2,2,2-tetrachloroethyl)benzamides 3 in high yields
by treatment with phosphorus pentachloride, as described
previously.29b,30 Products 3 were selectively monoalkoxy-
lated by simple treatment with a mixture of the correspond-
ing alcohol and triethylamine (ratio 1:1) to give the targeted
intermediates 4 in good to quantitative yields.24
To conclude, an effective method for the synthesis of previ-
ously unattainable (E)-4-alkoxy-2-aryl-5-chloro-2-thiazo-
lines is reported. Versatility, good yields, easy availability
of starting materials, mildness, and simple experimental
procedure are noteworthy advantages of this approach.
The viability of a direct transformation of intermediates 4
to products 7 based on previous results concerning the

9690
A. Guirado et al. / Tetrahedron 62 (2006) 9688–9693
3. Experimental
3.2.2. N-(2,2-Dichloro-1-ethoxyethyl)benzamide (5b).
Crystallization from petroleum ether gave white needles
(80%); mp 98–99 ꢁC (Found: C 50.47; H 4.95; N 5.37,
C11H13Cl2NO2 requires: C 50.40; H 5.00; N 5.34); 1H
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, 65.23, 72.67, 81.54, 127.24, 128.83, 132.42,
133.16, 167.59; MS m/z (%) 224 (4), 218 (14), 216 (22),
178 (11), 105 (100), 77 (58), 51 (18); IR (Nujol) 3211,
3.1. General
NMR spectra were determined on Bruker AV-200, Bruker
AV-300, or Bruker AV-400 with tetramethylsilane as internal
reference. Electron-impact mass spectra were obtained on
Thermoquest trace MS spectrometer under an ionizing volt-
age of 70 eV. FAB+ were obtained on Autospec 5000 VG
spectrometer. IR spectra (Nujol emulsions) were recorded
on a Nicolet Impact 400 spectrometer. Microanalyses were
performed on a Carlo Erba EA-1108 analyzer. Melting
1635, 1524, 1466, 1379, 1085, 791, 696 cmꢀ1
.
€
points were determined on a Buchi Melting point B-540,
and are uncorrected. Electrochemical experiments were
performed with an Amel 552 potentiostat coupled to an
Amel 721 integrator.
3.2.3. N-[2,2-Dichloro-1-(2-phenylethoxy)ethyl]benz-
amide (5c). Crystallization from petroleum ether gave white
needles (75%); mp 88 ꢁC (Found: C 60.45; H 4.99; N 4.16,
C17H17Cl2NO2 requires: C 60.37; H 5.07; N 4.14); 1H NMR
d (CDCl3, 400 MHz) 2.93 (t, 2H, J¼6.8 Hz), 3.89–3.94 (m,
2H), 5.76 (dd, 1H, J¼9.5, 2.3 Hz), 5.84 (d, 1H, J¼2.3 Hz),
6.59 (d, 1H, J¼9.5 Hz), 7.20–7.26 (m, 5H), 7.45 (t, 2H,
J¼7.7 Hz), 7.58 (t, 1H, J¼7.7 Hz), 7.71 (d, 2H,
J¼7.2 Hz); 13C NMR d (CDCl3, 100.4 MHz) 36.00, 70.17,
72.49, 81.59, 126.41, 127.17, 128.39, 128.75, 129.08,
132.39, 132.97, 138.29, 167.53; MS m/z (%) 216 (3), 182
(4), 105 (77), 104 (100), 91 (22), 77 (68); IR (Nujol) 3250,
3.2. Electrochemical preparation of N-(1-alkoxy-
2,2-dichloroethyl)benzamides (5)
Electrolysis of compounds 4 was carried out under 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 ꢁC by external cooling. The reduction was
performed in DMF (50 mL)–AcOH (1 mL)–LiClO4 0.5 M.
Anhydrous sodium carbonate (1 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 ꢀ1.7 V vs SCE. The duration
of the electrolyses ranged from 1.8 to 2.0 h. The average
current intensity was 10.7 mA/cm2 at the beginning, and
1.02 mA/cm2 at the end. The cell voltage values remained
below 5 V in all cases. The electricity consumption was
2 F/mol in all cases. Electrolyses carried out using NaBF4,
which is a less potentially hazardous electrolyte32 than
LiClO4, gave similar results. These syntheses were found
to be reproducible but with moderate current efficiency
(around 40%) by working in DMF (50 mL)–AcOH
(0.6 mL)–NaBF4 0.5 M and using graphite (ꢀ1.8 V vs
SCE) instead of mercury as cathodic material.
1638, 1525, 1467, 1347, 1278, 1122, 1081, 1027 cmꢀ1
.
3.2.4. N-[2,2-Dichloro-1-(2-phenylethoxy)ethyl]-
4-chlorobenzamide (5d). Crystallization from petroleum
ether gave white needles (78%); mp 91–93 ꢁC (Found: C
54.77; H 4.28; N 3.80, C17H16Cl3NO2 requires: C 54.79;
1
H 4.33; N 3.76); H NMR d (CDCl3, 400 MHz) 2.91 (t,
2H, J¼6.7 Hz), 3.86–3.96 (m, 2H), 5.72 (dd, 1H, J¼9.4,
2.3 Hz), 5.82 (d, 1H, J¼2.3 Hz), 6.50 (d, 1H, J¼9.4 Hz),
7.19–7.26 (m, 5H), 7.41 (d, 2H, J¼8.5 Hz), 7.62 (d, 2H,
J¼8.5 Hz); 13C NMR d (CDCl3, 100.4 MHz) 36.03, 70.29,
72.40, 81.73, 126. 44, 128.40, 128.61, 129.01, 129.09,
131.35, 138.33, 138.74, 166.48; MS m/z (%) 250 (2), 216
(3), 141 (44), 139 (85), 111 (49), 104 (100), 91 (37), 7
(19); IR (Nujol) 3287, 1653, 1526, 1464, 1379, 1344,
1102, 1018, 850, 793, 702 cmꢀ1
.
3.2.5. N-(2,2-Dichloro-1-benzyloxyethyl)-4-methylbenz-
amide (5e). Crystallization from petroleum ether gave white
needles (98%); mp 120–121 ꢁC (Found: C 60.33; H 5.10; N
4.11, C17H17Cl2NO2 requires: C 60.37; H 5.07; N 4.14); 1H
NMR d (CDCl3, 400 MHz) 2.42 (s, 3H), 4.71 (d, 1H, J¼
11.9 Hz), 4.77 (d, 1H, J¼11.9 Hz), 5.86–5.88 (m, 2H),
6.77 (d, 1H, J¼9.7 Hz), 7.26–7.42 (m, 7H), 7.69 (d, 2H,
J¼8.1 Hz); 13C NMR d (CDCl3, 100.4 MHz) 21.52, 71.07,
72.62, 80.96, 127.19, 128.01, 128.11, 128.51, 129.43,
130.13, 136.80, 143.08, 167.48; MS m/z (%) 230 (11), 196
(75), 160 (16), 119 (94), 91 (100), 77 (23), 65 (41); IR
(Nujol) 3275, 1645, 1522, 1505, 1462, 1344, 1098, 794,
All the electrolysis products were isolated by pouring the
catholyte solution into ice–water, and the resulting solids
were collected by filtration and dried under vacuo. Products
5 were isolated as white solids and were crystallized from
1
the appropriated solvents giving satisfactory IR, H NMR,
13C NMR, mass spectra, and elemental analyses.
3.2.1. N-(2,2-Dichloro-1-methoxyethyl)benzamide (5a).
Crystallization from petroleum ether gave white needles
(70%); mp 98–99 ꢁC (Found: C 48.21; H 4.37; N 5.70,
C10H11Cl2NO2 requires: C 48.41; H 4.47; N 5.65);
1H NMR d (CDCl3, 400 MHz) 3.53 (s, 3H), 5.70 (dd,
1H, J¼9.0, 2.2 Hz), 5.90 (d, 1H, J¼2.2 Hz), 6.82 (d, 1H,
J¼9.0 Hz), 7.46–7.59 (m, 3H), 7.84 (d, 2H, J¼7.3 Hz);
13C NMR d (CDCl3, 100.4 MHz) 56.88, 72.26, 82.91,
127.16, 128.78, 132.42, 132.94, 167.69; MS m/z (%) 215
(3), 182 (12), 176 (23), 164 (52), 105 (100), 77 (82); IR
(Nujol) 3222, 1646, 1526, 1460, 1343, 1276, 1191, 1117,
738, 695 cmꢀ1
.
3.2.6. N-[2,2-Dichloro-1-(4-methoxybenzyloxy)ethyl)]-
4-methylbenzamide (5f). Crystallization from a mixture
of petroleum ether and chloroform gave white needles
(72%); mp 97–99 ꢁC (Found: C 58.69; H 5.18; N 3.83,
C18H19Cl2NO3 requires: C 58.71; H 5.20; N 3.80); 1H
NMR d (CDCl3, 400 MHz) 2.42 (s, 3H), 3.79 (s, 3H), 4.63
(d, 1H, J¼11.7 Hz), 4.72 (d, 1H, J¼11.7 Hz), 5.82–5.85
1074, 1026, 784, 694 cmꢀ1
.

A. Guirado et al. / Tetrahedron 62 (2006) 9688–9693
9691
(m, 2H), 6.77 (d, 1H, J¼9.6 Hz), 6.87 (d, 2H, J¼8.6 Hz),
7.28 (d, 2H, J¼8.1 Hz), 7.32 (d, 2H, J¼8.6 Hz), 7.70 (d,
2H, J¼8.1 Hz); 13C NMR d (CDCl3, 100.8 MHz) 21.51,
55.22, 70.76, 72.70, 80.57, 113.90, 127.19, 128.73,
129.41, 129.87, 130.16, 143.04, 159.56, 167.43; FAB+ 368
(M++1, 30); IR (Nujol) 3289, 1639, 1614, 1535, 1504,
13C NMR d (CDCl3, 75.4 MHz) 58.25, 71.19, 87.45,
126.72, 128.73, 132.01, 140.97, 201.84; MS m/z (%) 263
(M+, 2), 227 (8), 192 (33), 164 (13), 121 (100), 104 (26),
77 (34); IR (Nujol) 3273, 1510, 1459, 1365, 1235, 1098,
1011, 959, 794, 697 cmꢀ1
.
1342, 1299, 1249, 1176, 1089, 1033, 788, 764 cmꢀ1
.
3.3.2. N-(2,2-Dichloro-1-ethoxyethyl)thiobenzamide
(6b). Crystallization from hexane gave yellow needles
(70%); mp 90–91 ꢁC (Found: C 47.55; H 4.66; N 5.01; S
11.70, C11H13Cl2NOS requires: C 47.49; H 4.71; N 5.03;
S 11.53); 1H NMR d (CDCl3, 400 MHz) 1.31 (t, 3H,
J¼7.0 Hz), 3.84–3.96 (m, 2H), 6.06 (d, 1H, J¼2.2 Hz),
6.34 (dd, 1H, J¼8.4, 2.2 Hz), 7.41–7.45 (m, 2H), 7.52 (tt,
1H, J¼7.4, 1.2 Hz), 7.78–7.81 (m, 2H), 7.89 (d, 1H,
J¼8.4 Hz); 13C NMR d (CDCl3, 100.4 MHz) 14.99, 66.49,
71.39, 86.01, 126.70, 128.69, 131.96, 140.92, 201.26;
FAB+ 278 (M++1); IR (Nujol) 3287, 1500, 1464, 1378,
3.2.7. N-[2,2-Dichloro-1-(3,4,5-trimethoxybenzyloxy)-
ethyl]-2-chlorobenzamide (5g). Crystallization from a mix-
ture of petroleum ether and chloroform gave white needles
(80%); mp 93–96 ꢁC (Found: C 50.91; H 4.54; N 3.08,
C19H20Cl3NO5 requires: C 50.86; H 4.49; N 3.12); 1H
NMR d (CDCl3, 400 MHz) 3.83 (s, 3H), 3.86 (s, 6H), 4.67
(d, 1H, J¼11.9 Hz), 4.78 (d, 1H, J¼11.9 Hz), 5.84–5.87
(m, 2H), 6.66 (s, 2H), 6.97 (d, 1H, J¼9.9 Hz), 7.35–7.47
(m, 3H), 7.68 (dd, 1H, J¼7.5 Hz); 13C NMR d (CDCl3,
100.8 MHz) 56.17, 60.87, 71.23, 72.33, 80.63, 105.46,
127.35, 130.33, 130.57, 130.79, 132.06, 132.18, 133.75,
137.90, 153.34, 166.90; MS m/z (%) 449 (M++2, 1), 447
(M++1, 1), 216 (21), 196 (47), 181 (37), 169 (18), 139
(100), 111 (30), 75 (22); IR (Nujol) 3219, 3181, 1659,
1333, 1231, 1087, 947, 798, 694 cmꢀ1
.
3.3.3. N-[2,2-Dichloro-1-(2-phenylethoxy)ethyl]thiobenz-
amide (6c). Crystallization from petroleum ethergaveyellow
needles (76%); mp 86–87 ꢁC (Found: C 57.58; H 4.83; N
4.02; S 9.00, C17H17Cl2NOS requires: C 57.63; H 4.84; N
1591, 1525, 1506, 1328, 1231, 1128, 1078, 822, 760 cmꢀ1
.
1
3.95; S 9.05); H NMR d (CDCl3, 200 MHz) 2.97 (t, 2H,
3.2.8. N-[2,2-Dichloro-1-(3,4,5-trimethoxybenzyloxy-
ethyl)]-2-methylbenzamide (5h). Crystallization from
a mixture of petroleum ether and chloroform gave white
needles (81%); mp 107–109 ꢁC (Found: C 55.92; H 5.46;
N 3.30, C20H23Cl2NO5 requires: C 56.08; H 5.41; N 3.27);
1H NMR d (CDCl3, 400 MHz) 2.51 (s, 3H), 3.85 (s, 3H),
3.87 (s, 6H), 4.67 (d, 1H, J¼12.0 Hz), 4.76 (d, 1H,
J¼12 Hz), 5.83–5.87 (m, 2H), 6.49 (d, 1H, J¼9.5 Hz),
6.66 (s, 2H), 7.23–7.39 (m, 4H); 13C NMR d (CDCl3,
100.8 MHz) 20.02, 56.11, 60.81, 71.17, 72.51, 80.42,
105.28, 125.97, 126.66, 130.75, 131.36, 132.18, 134.85,
136.46, 137.86, 153.33, 170.16; MS m/z (%) 429 (M++2,
1), 427 (M+, 1), 198 (41), 196 (72), 181 (36), 169 (16),
160 (8), 148 (8), 138 (7), 119 (100), 91 (48), 65 (16); IR
(Nujol) 3292, 3243, 1679, 1592, 1511, 1332, 1236, 1130,
J¼6.2 Hz), 3.94–4.12 (m, 2H), 6.01 (d, 1H, J¼2.2 Hz), 6.32
(dd, 1H, J¼8.40, 2.2 Hz), 7.22–7.63 (m, 11H); 13C NMR
d (CDCl3, 50.4 MHz): 36.06, 71.28, 71.35, 86.11, 126.53,
126.71, 128.46, 128.61, 129.12, 131.94, 138.18, 140.68,
201.27; FAB+ 354 (M++1); IR (Nujol) 3288, 1499, 1459,
1367, 1226, 1144, 1088, 1011, 945, 794, 751, 695, 672 cmꢀ1
.
3.3.4. N-[2,2-Dichloro-1-(2-phenylethoxy)ethyl]-4-chloro-
thiobenzamide (6d). Crystallization from hexane gave
yellow needles (62%); mp 62–65 ꢁC (Found: C 52.62; H
4.22; N 3.55; S 8.23, C17H16Cl3NOS requires: C 52.52; H
4.15; N 3.60; S 8.25); 1H NMR d (CDCl3, 200 MHz) 2.92–
2.99 (m, 2H), 3.87–3.99 (m, 1H), 4.05–4.16 (m, 1H), 5.98
(d, 1H, J¼2.2 Hz), 6.25 (dd, 1H, J¼8.2, 2.2 Hz), 7.20–7.27
(m, 5H), 7.32 (d, 2H, J¼8.4 Hz), 7.50 (d, 2H, J¼8.4 Hz),
7.54 (d, 1H, J¼8.2 Hz); 13C NMR d (CDCl3, 50.4 MHz)
36.04, 71.20, 71.38, 86.17, 126.54, 128.01, 128.46, 128.73,
129.13, 138.27, 138.82, 199.57; MS m/z (%) 352 (1), 316
(6), 232 (6), 212 (7), 157 (15), 155 (36), 138 (26), 105
(100), 77 (30); IR (Nujol) 3297, 1594, 1507, 1468, 1406,
1091, 993, 784, 732 cmꢀ1
.
3.3. Preparation of N-(1-alkoxy-2,2-dichloroethyl)thio-
benzamides (6)
A toluene solution (50 mL) of 5 (3 mmol) and LR (3 mmol)
was refluxed for 1 h. After cooling, the suspended solid was
filtered off and the solvent was evaporated under reduced
pressure. The products were isolated by silica gel column
chromatography. Products 6a–e (ethyl acetate–hexane 1:6);
product 6f (ethyl acetate–hexane 1:3); product 6g (diethyl
ether–hexane 1:1), and product 6h (dichloromethane–
hexane 2:3). Afterward the yellow solids were crystallized
from the appropriated solvents. All compounds gave satis-
factory IR, 1H NMR, 13C NMR, mass spectra, and elemental
analyses.
1371, 1239, 1094, 1013, 948, 841, 793, 762, 701 cmꢀ1
.
3.3.5. N-(2,2-Dichloro-1-benzyloxyethyl)-4-methylthio-
benzamide (6e). Crystallization from petroleum ether
gave yellow needles (64%); mp 88 ꢁC (Found: C 57.72; H
4.78; N 3.99; S 9.00, C17H17Cl2NOS requires: C 57.63; H
1
4.84; N 3.95; S 9.05); H NMR d (CDCl3, 400 MHz) 2.38
(s, 3H), 4.87 (s, 2H), 6.02 (d, 1H, J¼2.2 Hz), 6.43 (dd, 1H,
J¼8.0, 2.2 Hz), 7.19 (d, 2H, J¼7.9 Hz), 7.30–7.43 (m,
5H), 7.58 (d, 2H, J¼8.2 Hz), 7.83 (d, 1H, J¼8.0 Hz); 13C
NMR d (CDCl3, 100.8 MHz) 21.40, 71.45, 72.50, 85.77,
126.75, 128.10, 128.35, 128.63, 129.26, 136.60, 137.98,
142.81, 200.89; MS m/z (%) 318 (1), 262 (6), 247 (9), 212
(51), 176 (29), 135 (97), 118 (49), 91 (100), 65 (33); IR
(Nujol) 3297, 1492, 1458, 1366, 1325, 1230, 1181, 1139,
3.3.1. N-(2,2-Dichloro-1-methoxyethyl)thiobenzamide
(6a). Crystallization from hexane gave yellow prisms
(79%); mp 100–101 ꢁC (Found: C 45.62; H 4.13; N 5.22;
S 12.08, C10H11Cl2NOS requires: C 45.47; H 4.20; N
5.30; S 12.14); 1H NMR d (CDCl3, 300 MHz) 3.66 (s,
3H), 6.06 (d, 1H, J¼2.1 Hz), 6.29 (dd, 1H, J¼8.7, 2.1 Hz),
7.43–7.53 (m, 3H), 7.79–7.82 (m, 2H), 7.90 (br s, 1H);
1076, 1035, 925, 786, 756, 706, 662 cmꢀ1
.
3.3.6. N-[2,2-Dichloro-1-(4-methoxybenzyloxy)ethyl]-4-
methylthiobenzamide (6f). Crystallization from a mixture

9692
A. Guirado et al. / Tetrahedron 62 (2006) 9688–9693
of hexane and dichloromethane gave yellow prisms (95%);
mp 92–94 ꢁC (Found: C 56.38; H 5.07; N 3.55; S 8.31,
C18H19Cl2NO2S requires: C 56.25; H 4.98; N 3.64; S 8.34);
1H NMR. d (CDCl3, 400 MHz) 2.39 (s, 3H), 3.79 (s, 3H),
4.80 (s, 2H), 6.00 (d, 1H, J¼2.2 Hz), 6.38 (dd, 1H, J¼8.3,
2.2 Hz), 6.88 (d, 2H, J¼8.7 Hz), 7.20 (d, 2H, J¼8.1 Hz),
7.35 (d, 2H, J¼8.7 Hz), 7.61 (d, 2H, J¼8.3 Hz), 7.81 (d,
1H, J¼8.1 Hz); 13C NMR d (CDCl3, 100.8 MHz) 21.42,
55.25, 71.50, 72.25, 85.50, 114.01, 126.76, 128.53, 129.25,
129.97, 137.98, 142.80, 159.76, 200.70; FAB+ 384 (M++1,
13); IR (Nujol) 3379, 3277, 1610, 1513, 1489, 1342, 1248,
128.94, 132.10, 132.49, 170.08; FAB+ 228 (M++1); IR
2931, 2834, 1606, 1527, 1448, 1335, 1308, 1229, 1092,
1035, 944, 909, 814, 767, 733, 690 cmꢀ1
.
3.4.2. 5-Chloro-4-ethoxy-2-phenyl-2-thiazoline (7b).
Chromatography (silica gel, hexane–ethyl acetate 6:1)
gave yellow oil (79%); (Found: C 54.73; H 4.89; N 5.86;
S 13.32, C11H12ClNOS requires: C 54.65; H 5.00; N 5.79;
1
S 13.26); H NMR d (CD3COCD3, 300 MHz) 1.20 (t, 3H,
J¼6.0 Hz), 3.79–3.91 (m, 2H), 6.00 (d, 1H, J¼0.9 Hz)
6.08 (d, 1H, J¼0.9 Hz), 7.53–7.61 (m, 3H), 7.89–7.92 (m,
2H); 13C NMR d (CD3COCD3, 75.4 MHz) 15.59, 65.54,
71.58, 115.04, 129.53, 129.78, 130.81, 133.39, 169.33; MS
m/z (%) 241 (M+, 7), 206 (14), 196 (8), 161 (15), 138 (20),
104 (100), 93 (12), 77 (21), 58 (15); IR 2979, 2900, 1611,
1452, 1326, 1231, 1176, 1090, 1037, 942, 813, 769,
1176, 1076, 935, 821, 789 cmꢀ1
.
3.3.7. N-[2,2-Dichloro-1-(3,4,5-trimethoxybenzyl-
oxy)ethyl]-2-chlorothiobenzamide (6g). Crystallization
from hexane gave pale yellow needles (94%); mp 146–
147 ꢁC (Found: C 48.89; H 4.34; N 3.10; S 7.01,
C19H20Cl3NO4S requires: C 49.10; H 4.34; N 3.01; S
6.90); 1H NMR. d (CDCl3, 400 MHz) 3.85 (s, 3H), 3.87 (s,
6H), 4.77 (d, 1H, J¼11.9 Hz), 4.88 (d, 1H, J¼11.9 Hz),
5.99 (d, 1H, J¼2.3 Hz), 6.38 (dd, 1H, J¼8.4, 2.3 Hz), 6.67
(s, 2H), 7.30–7.42 (m, 3H), 7.51 (dd, 1H, J¼7.1, 2.1 Hz),
7.84 (d, 1H, J¼8.4 Hz); 13C NMR d (CDCl3, 100.4 MHz)
56.12, 60.82, 71.08, 72.29, 84.49, 105.64, 127.18, 128.12,
130.09, 130.97, 131.48, 137.99, 141.21, 153.25, 200.05;
FAB+ 464 (M++1, 2); IR (Nujol) 3180, 1597, 1542, 1508,
691 cmꢀ1
.
3.4.3. 5-Chloro-2-phenyl-4-(2-phenylethoxy)-2-thiazo-
line (7c). Chromatography (silica gel, hexane–ethyl acetate
6:1) gave yellow oil (80%); (Found: C 64.40; H 5.11; N 4.43;
S 10.17, C17H16ClNOS requires: C 64.24; H 5.07; N 4.41; S
10.09); 1H NMR d (CDCl3, 200 MHz) 2.94 (t, 2H,
J¼7.2 Hz), 3.87–4.15 (m, 2H), 5.59 (d, 1H, J¼1.2 Hz),
6.08 (d, 1H, J¼1.2 Hz), 7.23–7.30 (m, 5H), 7.39–7.48 (m,
3H), 7.86 (dd, 2H, J¼8.0, 1.4 Hz); 13C NMR d (CDCl3,
50.4 MHz) 36.28, 70.14, 70.34, 114.31, 126.33, 128.37,
128.67, 128.88, 128.92, 132.11, 132.42, 138.25, 169.80;
FAB+ 318 (M++1); IR 3063, 3023, 2928, 1607, 1525, 1497,
1332, 1235, 1153, 1128, 1099, 974, 943 cmꢀ1
.
3.3.8. N-[2,2-Dichloro-1-(3,4,5-trimethoxybenzyloxy)-
ethyl]-2-methylthiobenzamide (6h). Crystallization from
a mixture of petroleum ether and chloroform gave pale
yellow prisms (68%); mp 128–130 ꢁC (Found: C 54.14; H
5.28; N 3.20; S 7.20, C20H23Cl2NO4S requires: C 54.06; H
1451, 1327, 1234, 1173, 1090, 908, 816, 733, 695 cmꢀ1
.
3.4.4. 5-Chloro-2-(4-chlorophenyl)-4-(2-phenylethoxy)-
2-thiazoline (7d). Chromatography (silica gel, hexane–ethyl
acetate 6:1) gave yellow oil (94%); (Found: C 58.10; H 4.30;
N 4.00; S 9.03, C17H15Cl2NOS requires: C 57.96; H 4.29; N
1
5.22; N 3.15; S 7.22); H NMR. d (CDCl3, 400 MHz) 2.43
(s, 3H), 3.86 (s, 3H), 3.87 (s, 6H), 4.77 (d, 1H, J¼11.9 Hz),
4.84 (d, 1H, J¼11.9 Hz), 5.99 (d, 1H, J¼2.2 Hz), 6.44 (dd,
1H, J¼8.5 Hz, J¼2.2 Hz), 6.67 (s, 2H), 7.21–7.32 (m, 4H),
7.67 (d, 1H, J¼8.5 Hz); 13C NMR d (CDCl3, 100.8 MHz)
19.68, 56.14, 60.84, 71.38, 72.52, 84.34, 105.45, 126.11,
126.38, 129.58, 131.01, 131.69, 132.90, 137.99, 143.21,
153.31, 204.61; FAB+ 444 (M++1, 5); IR (Nujol) 3189, 1598,
1
3.98; S 9.10); H NMR d (CDCl3, 400 MHz) 2.95 (t, 2H,
J¼7.2 Hz), 3.94 (dt, 1H, J¼9.5, 7.2 Hz), 4.09 (dt, 1H,
J¼9.5, 7.2 Hz), 5.63 (d, 1H, J¼1.2 Hz), 6.05 (d, 1H, J¼
1.2 Hz), 7.20–7.28 (m, 5H), 7.41 (dd, 2H, J¼6.7, 2.0 Hz),
7.80 (dd, 2H, J¼6.7, 2.0 Hz); 13C NMR d (CDCl3,
100.4 MHz) 36.33, 70.28, 70.54, 114.35, 126.41, 128.44,
128.91, 129.02, 130.19, 130.66, 138.27, 138.75, 168.62;
FAB+ 352 (M++1); IR 2919, 1603, 1491, 1401, 1311,
1508, 1332, 1236, 1151, 1130, 1091, 939, 786, 761 cmꢀ1
.
3.4. Preparation of (E)-4-alkoxy-2-aryl-5-chloro-
2-thiazolines (7)
1242, 1176, 1092, 944, 837, 739, 703 cmꢀ1
.
3.4.5. 4-Benzyloxy-5-chloro-2-(4-methylphenyl)-2-thia-
zoline (7e). Chromatography (silica gel, hexane–ethyl ace-
tate 6:1) gave yellow oil (96%); (Found: C 64.12; H 5.11;
N 4.31; S 10.16, C17H16ClNOS requires: C 64.24; H 5.07;
Sodium hydroxide (10 mmol) was added to acetonitrile
solutions of compounds 6 (1 mmol), and the reaction mix-
ture was stirred at room temperature for 6 h. After filtration
and evaporation of the solvent under reduced pressure,
compounds 7 were collected as yellow oils, and were puri-
fied by column chromatography. All novel compounds
1
N 4.41; S 10.09); H NMR d (CDCl3, 400 MHz) 2.41 (s,
3H), 4.80 (d, 1H, J¼11.7 Hz), 4.91 (d, 1H, J¼11.7 Hz),
5.73 (d, 1H, J¼1.2 Hz), 6.15 (d, 1H, J¼1.2 Hz), 7.24–7.38
(m, 7H), 7.77 (d, 2H, J¼8.2 Hz); 13C NMR d (CDCl3,
100.4 MHz) 21.62, 70.28, 71.23, 113.47, 128.00, 128.02,
128.50, 128.97, 129.40, 129.52, 137.24, 143.19, 170.07;
FAB+ 318 (M++1); IR 3031, 2925, 1605, 1507, 1455,
1
gave satisfactory elemental analyses and IR, H NMR, 13C
NMR, and mass spectra (FAB+).
3.4.1. 5-Chloro-2-phenyl-4-methoxy-2-thiazoline (7a).
Chromatography (silica gel, hexane–ethyl acetate 6:1)
gave yellow oil (74%); (Found: C 52.83; H 4.49; N 6.07;
S 14.14, C10H10ClNOS requires: C 52.75; H 4.43; N 6.15;
1311, 1178, 1073, 940, 818, 734, 699 cmꢀ1
.
3.4.6. 5-Chloro-4-(4-methoxybenzyloxy)-2-(4-methyl-
phenyl)-2-thiazoline (7f). Chromatography (silica gel,
hexane–ethyl acetate 4:1) gave yellow oil (95%); (Found:
C 62.27; H 5.17; N 4.10; S 9.31, C18H18ClNO2S requires:
1
S 14.08); H NMR d (CDCl3, 400 MHz) 3.61 (s, 3H), 5.71
(d, 1H, J¼1.2 Hz), 6.00 (d, 1H, J¼1.2 Hz), 7.40–7.47 (m,
2H), 7.51–7.60 (m, 1H), 7.87–7.91 (m, 2H); 13C NMR
d (CDCl3, 100.8 MHz) 56.98, 69.79, 115.33, 128.71,
1
C 62.15; H 5.22; N 4.03; S 9.22); H NMR d (CDCl3,

A. Guirado et al. / Tetrahedron 62 (2006) 9688–9693
9693
Lett. 2001, 11, 2533; (c) Zarantonello, P.; Leslie, C. P.;
Ferrito, R.; Kazmierski, W. M. Bioorg. Med. Chem. Lett.
2002, 12, 561.
400 MHz) 2.41 (s, 3H), 3.81 (s, 3H), 4.74 (d, 1H, J¼11.3 Hz),
4.84 (d, 1H, J¼11.3 Hz), 5.70 (d, 1H, J¼
1.1 Hz), 6.13 (d, 1H, J¼1.1 Hz), 6.90 (d, 2H, J¼8.4 Hz),
7.25 (d, 2H, J¼8.3 Hz), 7.33 (d, 2H, J¼8.3 Hz), 7.78 (d,
2H, J¼8.4 Hz); 13C NMR d (CDCl3, 100.8 MHz) 21.62,
55.27, 70.34, 70.98, 113.17, 113.91, 128.97, 129.24,
129.40, 129.53, 129.83, 143.17, 159.49, 169.94; MS m/z
(%) 348 (M++1, 1), 350 (M++3, 1), 311 (1), 176 (33), 121
(100), 118 (14), 91 (10), 77 (12), 58 (7); IR 2999, 2954,
6. Wipf, P.; Reeves, J. T.; Balanchandran, R.; Day, B. W. J. Med.
Chem. 2002, 45, 1901.
7. Elliot, G. T.; Nagle, W. A.; Kelly, K. F.; McCollough, D.; Bona,
R. L.; Burns, E. R. J. Med. Chem. 1989, 32, 1039.
8. (a) Metzger, J. V. Comprehensive Heterocyclic Chemistry;
Katrizky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984;
Vol. 6, p 306; (b) Dondoni, A.; Merino, P. Comprehensive
Heterocyclic Chemistry II; Katrizky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3, p 373.
2931, 2834, 1608, 1514, 1465, 1303, 1248, 1178, 1038 cmꢀ1
.
3.4.7. 5-Chloro-2-(2-chlorophenyl)-4-(3,4,5-trimethoxy-
benzyloxy)-2-thiazoline (7g). Chromatography (silica gel,
hexane–ethyl acetate 3:1) gave yellow oil (93%); (Found:
C 53.39; H 4.52; N 3.23; S 7.58, C19H19Cl2NO4S requires:
ꢀ
9. (a) Galeotti, N.; Montagne, C.; Pioncet, J.; Jouin, P.
Tetrahedron Lett. 1992, 33, 2807; (b) Wipf, P.; Miller, C. P.
Tetrahedron Lett. 1992, 33, 6267.
10. Mahler, S. G.; Serra, G. L.; Antonow, D.; Manta, E.
Tetrahedron Lett. 2001, 42, 8143.
11. Lafargue, P.; Guenot, P.; Lellouche, J. P. Synlett 1995, 171.
12. Mulqueen, G. C.; Pattenden, G.; Whiting, D. A. Tetrahedron
1993, 49, 5359.
13. Vorbr€uggen, H.; Krolokiewick, K. Tetrahedron 1993, 49, 9353.
14. Bussaca, C. A.; Dong, Y.; Spinelli, E. M. Tetrahedron Lett.
1996, 37, 2935.
15. Pattenden, G.; Boden, C. D. J.; Ye, T. Synlett 1995, 417.
16. Charette, A. B.; Chua, P. J. Org. Chem. 1998, 63, 908.
17. (a) Nishio, T. Tetrahedron Lett. 1995, 36, 6113; (b) Nishio, T.
J. Org. Chem. 1997, 62, 1106.
18. Nishio, T.; Sekiguchi, H. Heterocycles 2002, 58, 203.
19. Wipf, P.; Miller, C. P.; Venkatraman, S.; Fritch, P. C.
Tetrahedron Lett. 1995, 36, 6395.
1
C 53.28; H 4.47; N 3.27; S 7.49); H NMR d (CDCl3,
400 MHz) 3.84 (s, 3H), 3.87 (s, 6H), 4.76 (d, 1H, J¼11.5 Hz),
4.88 (d, 1H, J¼11.5 Hz), 5.75 (d, 1H, J¼1.3 Hz), 6.15 (d, 1H,
J¼1.3 Hz), 6.63 (s 2H), 7.33–7.50 (m, 3H), 7.76 (dd, 1H,
J¼1.8, 7.6 Hz); 13C NMR d (CDCl3, 100.8 MHz) 56.12,
60.83, 70.60, 71.61, 105.20, 112.51, 126.92, 130.82,
131.28, 131.43, 132.14, 132.61, 132.86, 137.81, 153.35,
168.07; FAB+ 428 (M++1, 12); IR 3293, 3056, 2996, 2935,
2838, 1668, 1592, 1506, 1461, 1126, 833, 755 cmꢀ1
.
3.4.8. 5-Chloro-2-(2-methylphenyl)-4-(3,4,5-trimethoxy-
benzyloxy)-2-thiazoline (7h). Chromatography (silica gel,
hexane–ethyl acetate 3:1) gave yellow oil (95%); (Found:
C 58.94; H 5.33; N 3.38; S 7.82, C20H22ClNO4S requires:
1
C 58.89, H 5.44; N 3.43; S 7.86); H NMR d (CDCl3,
20. Fernandez, X.; Fellous, R.; Dun˜ach, E. Tetrahedron Lett. 2000,
41, 3381.
21. Katritzky, A. R.; Chunming, C.; Kazuyuki, S.; Sandeep, K. S.
J. Org. Chem. 2004, 69, 811.
22. Liu, B.; Davis, R.; Joshi, B.; Reynolds, D. W. J. Org. Chem.
2002, 67, 4595.
400 MHz) 2.61 (s, 3H), 3.83 (s, 3H), 3.87 (s, 6H), 4.76 (d,
1H, J¼12.0 Hz), 4.87 (d, 1H, J¼12.0 Hz), 5.72 (d, 1H,
J¼1.2 Hz), 6.19 (d, 1H, J¼1.2 Hz), 6.63 (s, 2H), 7.24–
7.41 (m, 3H), 7.59 (dd, 1H, J¼1.3, 7.6 Hz); 13C NMR
d (CDCl3, 100.8 MHz) 21.29, 56.06, 60.82, 70.19, 71.59,
105.01, 113.88, 125.95, 130.23, 131.06, 131.47, 131.52,
132.64, 137.66, 137.82, 153.31, 170.42; MS m/z (%) 407
(M+, 1), 225 (2), 196 (4), 182 (12), 181 (100), 176 (53),
151 (3), 148 (10), 117 (8), 90 (6), 77 (4); IR 3063, 2997,
2961, 2935, 2876, 1731, 1593, 1507, 1461, 1339, 1235,
ꢀ
23. (a) Guirado, A.; Andreu, R.; Galvez, J. Tetrahedron Lett. 1998,
39, 1071; (b) Guirado, A.; Andreu, R.; Galvez, J.; Jones, P.
ꢀ
Tetrahedron 2002, 58, 9853.
24. Guirado, A.; Andreu, R.; Martiz, B.; Galvez, J. Tetrahedron
ꢀ
1127 cmꢀ1
.
2004, 60, 987.
25. Guirado, A.; Andreu, R.; Galvez, J. Tetrahedron Lett. 1999, 40,
ꢀ
8163.
26. Guirado, A.; Andreu, R.; Galvez, J. Tetrahedron Lett. 2003, 44,
3809.
27. Cava, M. P.; Levinson, M. L. Tetrahedron 1985, 41, 5061.
28. (a) Jagodzinski, T. S. Chem. Rev. 2003, 103, 197; (b) Scheibye,
S.; Pedersen, B. S.; Lawesson, S. O. Bull. Soc. Chim. Belg.
1978, 87, 229.
ꢀ
Acknowledgements
We gratefully acknowledge the financial support of the Min-
ꢀ
isterio de Educacion y Ciencia (project CTQ2004-06427).
B.M. thanks the Fundacion CajaMurcia for a grant.
ꢀ
29. (a) Meldrum, A. N.; Bhojraj, M. G. J. Indian Chem. Soc. 1936,
ꢀ
13, 185; (b) Guirado, A.; Andreu, R.; Cerezo, A.; Galvez, J.
References and notes
Tetrahedron 2001, 39, 4925.
30. Guirado, A.; Andreu, R.; Zapata, A.; Cerezo, A.; Bautista, D.
Tetrahedron 2002, 58, 5087.
31. (a) Constantino, M. G.; Jose da Silva, G. V. Tetrahedron 1998,
54, 11363; (b) Gaudemer, A. Stereochemistry Fundamentals
and Methods; Kagan, H. B., Ed.; Georg Thieme: Stuttgart,
1997; Vol. 1, p 89.
32. Caution must be exercised when handling perchlorates in order
to exclude explosion risk. Evaporation of organic solutions
containing perchlorates requires to be carried out in vacuo
and at moderate temperature. Contact with strong acids must
be avoided.
1. (a) White, J. D.; Kim, T. S.; Nambu, M. J. Am. Chem. Soc.
1997, 119, 103; (b) White, J. D.; Kim, T. S.; Nambu, M.
J. Am. Chem. Soc. 1995, 117, 5612; (c) Lai, J.-H.; Yu, J.;
Makennen, B.; Falck, J. Tetrahedron Lett. 1996, 37, 7167.
2. (a) Boyce, R. J.; Mulqueen, C.; Pattenden, G. Tetrahedron Lett.
1994, 35, 5705; (b) Wipf, P.; Venkatraman, S. Synlett 1997, 1.
3. Carmeli, S.; Moore, R. E.; Patterson, G. M. L. Tetrahedron Lett.
1991, 32, 2593.
4. Chen, J.; Forsyth, C. J. Org. Lett. 2003, 5, 1281.
5. (a) Wipf, P.; Fritch, P. Tetrahedron Lett. 1994, 35, 5397; (b)
€
Einsiedel, J.; Hubner, H.; Gmeineer, P. Bioorg. Med. Chem.