Synthesis and X-ray molecular structure of N-(1-amino-2,2-dichloroethyl)benzamides

Article abstract of DOI:10.1016/S0040-4020(02)00464-7

Efficient procedures for the synthesis of N-(1-alkylamino-2,2-dichloroethyl)benzamides, N-(1-arylamino-2,2-dichloroethyl)benzamides and N-(1-amino-2,2-dichloroethyl)benzamides are reported. These compounds are of special interest as intermediates to acces

Full text of DOI:10.1016/S0040-4020(02)00464-7

TETRAHEDRON
Pergamon
Tetrahedron 58 )2002) 5087±5092
Synthesis and X-ray molecular structure
of N-ꢀ1-amino-2,2-dichloroethyl)benzamides
p
Antonio Guirado, Raquel Andreu, Andres Zapata, Alfredo Cerezo and Delia Bautista
Â
  Â
Departamento de Quõmica Organica, Facultad de Quõmica, Universidad de Murcia, Campus de Espinardo,
Apartado 4021, 30071 Murcia, Spain
Received 12 February 2002; revised 18 April 2002; accepted 26 April 2002
AbstractÐEf®cient procedures for the synthesis of N-)1-alkylamino-2,2-dichloroethyl)benzamides, N-)1-arylamino-2,2-dichloroethyl)benz-
amides and N-)1-amino-2,2-dichloroethyl)benzamides are reported. These compounds are of special interest as intermediates to access new
heterocyclic series. N-)2,2-dichlorovinyl)amides react with primary or secondary alkylamines to yield the title compounds in high to
quantitative yields. However, similar addition reactions with arylamines or ammonia are unsuccessful. In these cases the synthesis of the
targeted products may be achieved by starting from N-)1,2,2,2-tetrachloroethyl)benzamides which are aminated via nucleophilic substitution
yielding the corresponding N-)1-amino-2,2,2-trichloroethyl)benzamides. Finally, these compounds are selectively monodechlorinated by
electrochemical reduction at constant cathodic potential. The crystallographic X-ray structure of N-)2,2-dichloro-1-isopentylaminoethyl)-4-
methylbenzamide has been determined. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
N-)2,2-dichlorovinyl)amides 3 were prepared according to
our previously reported method,2 and were treated in dry
diethyl ether solution with 2 equiv. of the appropriate
primary or secondary alkylamine. From the course of
these reactions the generation at moderate rate of a single
compound was clearly observed. Abundant precipitates in
the majority of cases were forthcoming. Therefore, crude
reaction products of a high purity could easily be isolated in
high yields by simple ®ltration. These were crystallized and
identi®ed, after applying the usual spectroscopic techniques,
elemental analysis and X-ray crystallography, as the
aminated derivatives 4a±m. The formation of these
products involves nucleophilic addition of amino groups
across the carbon±carbon double bonds of vinylidene
dichorides 3. It should be noted that many reactions between
nucleophilic reagents and electronegatively substituted
ole®ns involve substitution processes.5±8 Addition reactions
between amines and alkenes normally require either acti-
vation of the double bond via metallation or amino group
activation in order to promote radical reactions.9 Given our
results, it is apparent that both geminal chlorine atoms
present in compounds 3 would cause a remarkable electro-
philic activity, suf®cient to permit the addition of alkyl-
amines without participation of any other factor. It was
also found, however, that similar reactions of N-)2,2-
dichlorovinyl)amides 3 with arylamines were unable to
provide the corresponding N-)1-arylamino-2,2-dichloro-
ethyl)benzamides 4n,o. The starting materials were recov-
ered unchanged in these cases. Such reaction failures appear
clearly attributable to the remarkably lower nucleophilicity
Chloralamides 1 are inexpensive and easily available
compounds that can be prepared by reaction of chloral
hydrate with carboxylic amides.1,2 As we reported, this
almost quantitative reaction marks the beginning of a new
synthetic route for heterocyclic compounds of signi®cant
interest. On this basis we accomplished the ®rst synthesis
of 4-alkylamino-2-aryl-2-oxazolines3 6 which gave access
to novel 2-imidazolidinones4 7. A common key step of this
preparative procedure implies the electrochemical reduc-
tion of N-)1-amino-2,2-dichloroethyl)benzamides 4. This
process promotes a direct conversion of intermediates 4 to
products 6. In order to increase the usefulness of this hetero-
cyclization methodology, we have given attention to the
development of ef®cient and general procedures for pre-
paring both types of intermediates, 3 and 4. A convenient
method to synthesize N-)2,2-dichlorovinyl)amides 3 was
established2 based on the treatment of chloralamides with
phosphorus pentachloride to give N-)1,2,2,2-tetrachloro-
ethyl)amides 2, which can be electrochemically converted
to the compounds 3 in fair to quantitative yields. We now
report the results of our research on the synthesis of inter-
mediates 4 )Scheme 1). Spectral and X-ray crystallographic
structural data of this little known class of compounds are
also reported.
Keywords: chloralamides; vinylidene dichlorides; vinylamides; electro-
synthesis; reduction.
p
Corresponding author. Tel.: 134-96-8367-490; fax: 134-96-8364-148;
e-mail: anguir@um.es
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020)02)00 464-7

5088
A. Guirado et al. / Tetrahedron 58 /2002) 5087±5092
Scheme 1.
of arylamines than alkylamines. The reaction with ammonia
also consistently failed. Attempts to promote the reactions
with the assistance of catalytic amounts of the correspond-
ing anilinium chlorides or ammonium chloride were simi-
larly unsuccessful, whereas those reactions carried out at a
relatively high temperature gave complex mixtures of
products, which were not identi®ed. Such adverse results
suggested our exploring an alternative synthetic route
based on performing the amination process sought, via
nucleophilic substitution rather than addition. In the ®rst
place N-)1,2,2,2-tetrachloroethyl)benzamide 2a )91%) was
prepared by reaction of 1a with phosphorus pentachloride.
The reactions of 2a with arylamines to yield N-)arylamino-
2,2,2-trichloroethyl)benzamides 5n,o were found to be
almost quantitative. The preparation of N-)amino-2,2,2-
trichloroethyl)benzamide 5p )75%) by reaction of 2a with
a relatively weak nucleophilic reagent such as ammonia
could also be ef®ciently achieved in this way. Finally, the
compounds 5n±p were converted to the desired N-)aryl-
amino-2,2-dichloroethyl)benzamides 4n,o and N-)amino-
2,2-dichloroethyl)benzamide 4p, respectively, in fair to
high yields, by selective electrochemical monodechlori-
nation reductions carried out under constant potential in a
protic medium.
Representative structural characteristics of compounds 4
were determined by X-ray crystallography of 4m. The
molecular structure found is illustrated in Fig. 1. Selected
intramolecular distances )crystallographic numbering of
atoms) and selected bond angles are given in Table 1. The

A. Guirado et al. / Tetrahedron 58 /2002) 5087±5092
5089
found to be feasible by an alternative procedure involving
amination of an easily available class of tetrachlorinated
derivatives followed by selective electrochemical reduction.
3. Experimental
3.1. General
NMR spectra were determined on Bruker AC-200 or Varian
300 Unity instruments with tetramethylsilane as internal
reference. Electron-impact mass spectra were obtained on
Hewlett-Packard 5995 and Autospect 5000 VG spectro-
meters with direct insertion probe and an ionizing voltage
of 70eV. 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 Ko¯er hot-plate melting
point apparatus, and are uncorrected. Electrochemical
experiments were performed with an Amel 557 potentiostat
coupled to an Amel 558 integrator.
Figure 1. Molecular structure of 4m, showing the crystallographic number-
ing system used.
adjacent molecules )Fig. 2) interact through one hydrogen
Ê
bond. Intermolecular bond distances: N´´´Oˆ2.925 A;
Ê
H´´´Oˆ2.189 A; O±H±N angleˆ1548.
In conclusion, it has been established in general that N-)2,2-
dichlorovinyl)benzamides undergo ef®cient addition reac-
tions with amines of relatively high nucleophilicity, such
as primary and secondary alkylamines, to yield the corre-
sponding N-)1-alkylamino-2,2-dichloroethyl)benzamides.
The failure of similar reactions with ammonia or arylamines
is attributable to their lower nucleophilicity. However, the
preparation of N-)1-amino-2,2-dichloroethyl)benzamides
and N-)1-arylamino-2,2-dichloroethyl)benzamides has been
Chloralamides 1, N-)1,2,2,2-tetrachloroethyl)benzamide 2,
and N-)2,2-dichlorovinyl)benzamides 3 were prepared as
previously described.1,2
3.2. Preparation of N-ꢀ1-alkylamino-2,2-dichloroethyl)-
benzamides 4a±m
To a solution of the appropriate dichlorovinylamide 3
)3 mmol) in dry ether )10mL) a solution of the correspond-
ing alkylamine )6 mmol) in dry ether )10mL) was added
dropwise and the reaction mixture was stirred at room
temperature for 24 h. The solid precipitated was ®ltered
off and was crystallized from the appropriate solvent. In
those cases where a precipitate was not formed the solvent
was evaporated under reduced pressure, leaving a solid
residue that was crystallized as above. Owing to the high
volatility of methylamine the reaction with this reagent was
carried out at 258C.
Table 1. Selected bond lengths and bond angles in crystal structure of 4m
Ê
Bond lengths )A)
Cl)1)±C)3)
O±C)1)
N)1)±C)1)
N)1)±C)2)
N)2)±C)2)
1.782)2)
1.235)2)
1.349)3)
1.453)3)
1.443)3)
N)2)±C)4)
C)1)±C)11)
C)2)±C)3)
C)14)±C)17)
1.470)3)
1.494)3)
1.531)3)
1.504)3)
Bond angles )8)
C)1)±N)1)±C)2)
C)2)±N)2)±C)4)
O±C)1)±N)1)
O±C)1)±C)11)
O±C)1)±C)11)
N)1)±C)1)±C)11)
N)2)±C)2)±N)1)
125.7)2)
N)2)±C)2)±C)3)
N)1)±C)2)±C)3)
C)2)±C)3)±Cl)1)
Cl)2)±C)3)±Cl)1)
N)2)±C)4)±C)5)
C)7)±C)6)±C)8)
107.5)2)
114.2)2)
123.7)2)
122.1)2)
122.1)2)
114.2)2)
114.6)2)
110.5)2)
111.1)2)
108.65)11)
110.2)2)
110.5)2)
3.3. Electrochemical generation of products 4n±p
Preparative electrolyses were carried out under a constant
Figure 2. A perspective of the crystal packing of 4m, showing the hydrogen interactions.

5090
A. Guirado et al. / Tetrahedron 58 /2002) 5087±5092
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 188C by external cooling. The reductions
were performed in MeCN±LiClO4, 0.5 M of which 35 mL
and 15 mL, approximately, were placed, respectively, in
the cathodic and the anodic compartments. Acetic acid
)5 mmol) was added to the cathodic compartment. Solutions
of compounds 5 )5 mmol) were electrolyzed under the
following cathodic potentials: 5n )21.30); 5o )21.70); 5p
)21.20V vs SCE). The electricity consumption was
2 F/mol in all cases. The duration of the electrolyses ranged
from 1.6 to 1.8 h. The average current intensity was 240mA
at the beginning and 15 mA at the end. All electrolysis
products were isolated by removing the solvent in
vacuo.10 The residue was then shaken with water, leaving
a white solid that was collected by ®ltration, was air-dried
and crystallized from the appropriate solvent. The product
4p was puri®ed by column chromatography )silica gel,
hexane±ethyl acetate; 1:1).
3.3.4. N-ꢀ2,2-Dichloro-1-isopropylaminoethyl)benzamide
ꢀ4d). )76%), white needles )pet ether) mp 808C dec. )Found:
C 52.60; H 5.71; N 10.13; C12H16Cl2N2O requires: C 52.38;
1
H 5.86; N 10.18); H NMR d )CDCl3, 200 MHz): 1.11 )d,
3H, Jˆ6.4 Hz), 1.13 )d, 3H, Jˆ6.2 Hz), 2.12 )s br, 1H), 3.05
)sept., 1H, Jˆ6.2 Hz), 5.38 )dd, 1H, Jˆ8.2, 2.5 Hz), 6.02 )d,
1H, Jˆ2.5 Hz), 6.67 )d, 1H, Jˆ8.2 Hz), 7.39±7.53 )m, 3H),
7.81 )d, 1H, Jˆ7.5 Hz); 13C NMR d )CDCl3, 50.4 MHz):
22.39 )CH3), 23.85 )CH3), 45.98 )CH), 67.18 )CH), 74.82
)CHCl2), 127.10)CH), 128.69 )CH), 132.07 )CH), 133.51
)C), 167.50)CO); FAB 1: 275 )M111); IR )Nujol): 3314,
1642, 1536, 1465, 1378, 1346, 1276, 1078, 1001, 758 cm21
.
3.3.5. N-ꢀ2,2-Dichloro-1-diethylaminoethyl)benzamide
ꢀ4e). )99%), white needles )pet ether) mp 91±928C.
)Found: C 54.00; H 6.52; N 9.49; C13H19Cl2N2O requires:
1
C 53.80; H 6.60; N 9.65); H NMR d )CDCl3, 200 MHz):
1.10)t, 6H, Jˆ7.1 Hz), 2.57±2.85 )m, 4H), 5.44 )dd, 1H,
Jˆ9.2, 4.7 Hz), 5.91 )d, 1H, Jˆ4.6 Hz), 6.94 )d, 1H, Jˆ
9.1 Hz), 7.39±7.56 )m, 3H), 7.81 )d, 2H, Jˆ6.8 Hz); 13C
NMR d )CDCl3, 50.4 MHz): 13.50 )CH3), 43.81 )CH2),
71.33 )CH), 74.28 )CHCl2), 127.14 )CH), 128.74 )CH),
132.02 )CH), 133.83 )C), 167.95 )CO); FAB1: 289
)M111); IR )Nujol): 3233, 1633, 1529, 1464, 1376, 1335,
3.3.1. N-ꢀ1-Benzylamino-2,2-dichloroethyl)benzamide
ꢀ4a). )70%), white needles )pet ether±dichloromethane)
1209, 1076, 771, 744, 706 cm21
.
mp 1368C. )Found:
C
59.38;
H
5.02;
N
8.53;
C16H16Cl2N2O requires: C 59.46; H 4.99; N 8.67); 1H
NMR d )CDCl3, 200 MHz): 2.18 )s br, 1H), 3.96 )s, 2H),
5.37 )dd, 1H, Jˆ8.3, 2.5 Hz), 6.03 )d, 1H, Jˆ2.5 Hz), 6.52
)d, 1H, Jˆ8.3 Hz), 7.25±7.55 )m, 8H), 7.75 )d, 2H,
Jˆ8.1 Hz); 13C NMR d )CDCl3, 50.4 MHz): 50.55 )CH2),
68.81 )CH), 74.47 )CHCl2), 127.15 )CH), 127.47 )CH),
128.21 )CH), 128.66 )CH), 128.78 )CH), 132.21 )CH),
133.47 )C), 139.25 )C), 167.66 )CO); FAB1: 323
)M111); IR )Nujol): 3359, 3305, 1623, 1510, 1487, 1328,
3.3.6. N-ꢀ1-Cyclohexylamino-2,2-dichloroethyl)benzamide
ꢀ4f). )66%), white needles )pet ether) mp 121±1228C.
)Found: C 40.31; H 2.96; N 5.27; C15H20Cl2N2O requires:
1
C 40.26; H 3.00; N 5.22); H NMR d )CDCl3, 200 MHz):
1.20±2.04 )m, 11H), 2.67 )s br, 1H), 5.40 )dd, 1H, Jˆ8.1,
2.4 Hz), 6.03 )d, 1H, Jˆ2.4 Hz), 6.52 )d, 1H, Jˆ8.1 Hz),
7.45±7.54 )m, 3H), 7.78 )d, 2H, Jˆ7.4 Hz); 13C NMR d
)CDCl3, 50.4 MHz): 24.57 )CH2), 24.86 )CH2), 25.91
)CH2), 32.92 )CH2), 34.39 )CH2), 53.86 )CH), 66.95 )CH),
74.88 )CHCl2), 127.13 )CH), 128.77 )CH), 132.11 )CH),
133.58 )C), 167.33 )CO); FAB1: 315 )M111); IR )Nujol):
1276, 1008, 804, 796, 725, 700 cm21
.
3.3.2. N-ꢀ2,2-Dichloro-1-methylaminoethyl)benzamide
ꢀ4b). )86%), white needles )pet ether±dichloromethane)
mp 125±1268C. )Found: C 48.38; H 4.96; N 11.23;
3331, 1629, 1513, 1464, 1377, 1140, 794, 695 cm21
.
3.3.7. N-ꢀ1-Benzylamino-2,2-dichloroethyl)-2-chlorobenz-
amide ꢀ4g). )90%), white needles )pet ether) mp 121±1238C.
)Found: C 56.99; H 6.45; N 8.93; C16H15Cl3N2O requires: C
57.15; H 6.39; N 8.89); 1H NMR d )CDCl3, 300 MHz): 2.08
)s br, 1H), 3.09 )d, 1H, Jˆ12.2 Hz), 4.05 )d, 1H, Jˆ
12.2 Hz), 5.39 )dd, 1H, Jˆ8.7, 2.7 Hz), 6.03 )d, 1H, Jˆ
2.7 Hz), 6.63 )d, 1H, Jˆ8.4 Hz), 7.26±7.46 )m, 8H), 7.66
)d, 1H, Jˆ7.2 Hz); 13C NMR d )CDCl3, 75.4 MHz): 50.41
)CH2), 68.75 )CH), 74.28 )CHCl2), 127.33 )CH), 127.53
)CH), 128.36 )CH), 128.66 )CH), 130.47 )CH), 130.50
)CH), 130.77 )C), 131.91 )CH), 134.24 )C), 139.09 )C),
166.76 )CO); MS m/z )%): 286 )1), 273 )M12CHCl2, 2),
201 )1), 166 )4), 139 )49), 111 )20), 106 )30), 91 )100), 75
)19); IR )Nujol): 3307, 1657, 1532, 1464, 1378, 1344, 1159,
1
C10H12Cl2N2O requires: C 48.60; H 4.89; N 11.34); H
NMR d )DMSO-d6, 200 MHz): 2.14 )s br, 1H), 2.37 )s,
3H), 5.00 )s br, 1H), 6.26 )d, 1H, Jˆ4.0Hz), 7.46±7.62
)m, 3H), 7.91 )d, 2H, Jˆ8.1 Hz), 8.58 )d, 1H, Jˆ7.8 Hz);
13C NMR d )DMSO-d6, 50.4 MHz): 30.00 )CH3), 68.54
)CH), 72.25 )CHCl2), 124.72 )CH), 125.71 )CH), 128.97
)CH), 131.05 )C), 164.14 )CO); FAB1: 247 )M111); IR
)Nujol): 3332, 3310, 1647, 1524, 1464, 1378, 1108, 973,
765, 710cm 21
.
3.3.3. N-ꢀ2,2-Dichloro-1-propylaminoethyl)benzamide
ꢀ4c). )68%), white needles )ether) mp 101±1038C. )Found:
C 52.51; H 5.93; N 10.23; C12H16Cl2N2O requires: C 52.38;
1
H 5.86; N 10.18); H NMR d )CDCl3, 200 MHz): 0.91 )t,
1135, 1081, 974, 779, 754 cm21
.
3H, Jˆ7.3 Hz), 1.45±1.57 )m, 2H), 1.90)s br, 1H), 2.69±
2.73 )m, 2H), 5.31 )dd, 1H, Jˆ8.0, 2.5 Hz), 6.02 )d, 1H,
Jˆ2.5 Hz), 6.75 )d, 1H, Jˆ8.0Hz), 7.43±7.53 )m, 3H),
7.81 )dd, 2H, Jˆ8.0, 1.6 Hz); 13C NMR d )CDCl3,
50.4 MHz): 11.61 )CH3), 23.05 )CH2), 48.26 )CH2), 69.05
)CH), 74.46 )CHCl2), 127.11 )CH), 128.69 )CH), 132.08
)CH), 133.48 )C), 167.73 )CO); FAB1: 275 )M111); IR
)Nujol): 3280, 1665, 1644, 1538, 1469, 1380, 1342, 1123,
3.3.8. N-ꢀ1-Benzylamino-2,2-dichloroethyl)-3-chloro-
benzamide ꢀ4h). )98%), white needles )pet ether±dichloro-
methane) mp 1288C. )Found: C 53.88; H 4.28; N 7.77;
C16H15Cl3N2O requires: C 53.73; H 4.23; N 7.83); 1H
NMR d )CDCl3, 300 MHz): 2.20 )s br, 1H), 3.95 )s, 2H),
5.35 )dd, 1H, Jˆ8.4, 2.4 Hz), 6.02 )d, 1H, Jˆ2.7 Hz), 6.46
)d, 1H, Jˆ8.1 Hz), 7.26±7.68 )m, 9H); 13C NMR d )CDCl3,
75.4 MHz): 50.71 )CH2), 69.13 )CH), 74.31 )CHCl2),
780, 718 cm21
.

A. Guirado et al. / Tetrahedron 58 /2002) 5087±5092
5091
125.20)CH), 127.49 )CH), 127.57 )CH), 128.18 )CH),
128.72 )CH), 130.08 )CH), 132.20 )CH), 135.00 )C),
135.23 )C), 139.26 )C), 166.32 )CO); MS m/z )%): 328
)1), 285 )2), 273 )6), 166 )11), 156 )5), 141 )28), 111
)43), 106 )87), 91 )100), 75 )16); IR )Nujol): 3293, 1634,
CHCl2, 6), 119 )100), 91 )54), 77 )2), 65 )27); IR )Nujol):
3244, 1645, 1538, 1463, 1377, 1338, 1271, 1082, 1031,
777 cm21
.
3.3.13. N-ꢀ2,2-Dichloro-1-isopentylaminoethyl)-4-methyl-
benzamide ꢀ4m). )73%), white needles )pet ether) mp
89±908C. )Found: C 56.58; H 7.03; N 8.74; C15H22Cl2N2O
1523, 1465, 1378, 1037, 1009, 794, 732 cm21
.
1
3.3.9.
N-ꢀ1-Butylamino-2,2-dichloroethyl)-4-chloro-
requires: C 56.79; H 6.99; N 8.83); H NMR d )CDCl3,
benzamide ꢀ4i). )98%), white needles )pet ether) mp 89±
928C. )Found: C 48.04; H 5.16; N 8.50; C13H17Cl3N2O
requires: C 48.24; H 5.29; N 8.66); H NMR d )CDCl3,
300 MHz): 0.87 )d, 3H, Jˆ6.6 Hz), 0.88 )d, 3H, Jˆ
6.6 Hz), 1.34±1.45 )m, 2H), 1.61±1.66 )m, 1H), 1.72 )br
s, 1H), 2.40)s, 3H), 2.73±2.82 )m, 2H), 5.30)dd, 1H,
Jˆ8.2, 2.7 Hz), 6.02 )d, 1H, Jˆ2.4 Hz), 6.49 )d, 1H, Jˆ
8.2 Hz), 7.25 )d, 2H, Jˆ7.5 Hz), 7.70)d, 2H, Jˆ8.4 Hz);
13C NMR d )CDCl3, 75.4 MHz): 21.43 )CH3), 22.47 )CH3),
1
300 MHz): 0.90 )t, 3H, Jˆ7.2 Hz), 1.31±1.49 )m, 4H),
2.70±2.79 )m, 2H), 5.29 )dd, 1H, Jˆ8.5, 2.1 Hz), 6.02 )d,
1H, Jˆ2.4 Hz), 6.60)d, 1H, Jˆ8.1 Hz), 7.41 )d, 2H, Jˆ
8.4 Hz), 7.74 )d, 2H, Jˆ8.4 Hz); 13C NMR d )CDCl3,
22.56 )CH3), 25.83 )CH), 38.90)CH ), 44.63 )CH2), 69.05
2
75.4 MHz): 13.90)CH ), 20.24 )CH2), 32.05 )CH2), 46.26
)CH), 74.47 )CHCl2), 127.05 )CH), 129.32 )CH), 131.16
)C), 142.56 )C), 167.45 )CO); MS m/z )%): 280)M 12
HCl, 1), 233 )M12CHCl2, 3), 224 )2), 189 )3), 146 )3),
136 )7), 119 )100), 91 )48), 65 )21); IR )Nujol): 3323,
3
)CH2), 69.27 )CH), 74.41 )CHCl2), 128.58 )CH), 129.00
)CH), 131.95 )C), 138.42 )C), 166.66 )CO); MS m/z )%):
286 )M12HCl, 1), 239 )M12CHCl2, 6), 156 )7), 139 )100),
111 )53), 90 )10), 84 )20), 77 )5); IR )Nujol): 3279, 1640,
1644, 1536, 1468, 1377, 1121, 965, 840, 770 cm21
.
1536, 1464, 1376, 1340, 1127, 1012, 845, 773, 755 cm21
.
3.3.14. N-ꢀ2,2-Dichloro-1-phenylaminoethyl)benzamide
ꢀ4n). )87%), white needles )pet ether±dichloromethane)
mp 146±1498C. )Found: C 57.97; H 4.78; N 8.98;
C15H15Cl2N2O requires: C 58.08; H 4.87; N 9.03); 1H
NMR d )CDCl3, 300 MHz): 4.56 )br s, 1H), 6.05 )dd, 1H,
Jˆ7.2, 2.7 Hz), 6.16 )d, 1H, Jˆ2.4 Hz), 6.57 )d, 1H, Jˆ
7.5 Hz), 6.76±6.86 )m, 3H), 7.19±7.25 )m, 2H), 7.38±
7.54 )m, 3H), 7.73±7.77 )m, 2H); 13C NMR d )CDCl3,
75.4 MHz): 65.22 )CH), 73.65 )CHCl2), 114.05 )CH),
119.94 )CH), 127.19, )CH), 128.81 )CH), 129.71 )CH),
132.35 )CH), 133.14 )C), 144.15 )C), 167.54 )CO); MS
m/z )%): 308 )M1, 1), 272 )1), 137 )2), 225 )15), 187 )2),
152 )2), 122 )18), 105 )100), 93 )31), 77 )98); IR )Nujol):
3416, 3312, 1629, 1607, 1504, 1484, 1311, 1134, 1080,
3.3.10. N-ꢀ1-Benzylamino-2,2-dichloroethyl)-4-nitrobenz-
amide ꢀ4j). )72%), yellow powder )ethyl acetate±hexane)
mp 1368C. )Found:
C 51.97; H 4.04; N 11.23;
1
C16H15Cl2N3O3 requires: C 52.19; H 4.11; N 11.41); H
NMR d )CDCl3, 300 MHz): 2.04 )br s, 1H), 3.94 )d, 1H,
Jˆ15.8 Hz), 4.00 )d, 1H, Jˆ15.8 Hz), 5.38 )dd, 1H, Jˆ8.4,
2.4 Hz), 6.03 )d, 1H, Jˆ2.5 Hz), 6.47 )d, 1H, Jˆ8.3 Hz),
7.23±7.37 )m, 5H), 7.83 )d, 2H, Jˆ8.7 Hz), 8.27 )d, 2H,
Jˆ8.7 Hz); 13C NMR d )CDCl3, 50.4 MHz): 50.72 )CH2),
69.27 )CH), 74.05 )CHCl2), 123.87 )CH), 127.52 )CH),
128.05 )CH), 128.27 )CH), 128.70 )CH), 138.93 )C),
139.15 )C), 149.89 )C), 165.55 )CO); MS m/z )%): 368
)M111, 1), 209 )2), 195 )4), 166 )31), 150)87), 120)14),
106 )21), 91 )100), 77 )14); IR )Nujol): 3288, 1639, 1599,
1063, 792, 753 cm21
.
1524, 1464, 1377, 1344, 1318, 870, 846, 796 cm21
.
3.3.15. N-[2,2-Dichloro-1-ꢀ4-methoxyphenylamino)ethyl]-
benzamide ꢀ4o). )80%), white needles )pet ether±dichloro-
methane) mp 120±1218C. )Found: C 56.71; H 4.80; N 8.30;
C16H16Cl2N2O2 requires: C 56.65; H 4.75; N 8.26); 1H NMR
d )CDCl3, 200 MHz): 3.71 )s, 3H), 4.31 )d, 1H, Jˆ8.8 Hz),
5.96 )td, 1H, Jˆ8.4, 2.4 Hz), 6.14 )d, 1H, Jˆ2.4 Hz), 6.60
)d, 1H, Jˆ7.6 Hz), 6.76 )d, 4H, Jˆ3.3 Hz), 7.36±7.51 )m,
3H), 7.72±7.76 )m, 2H); 13C NMR d )CDCl3, 50.4 MHz):
55.72 )CH3O), 66.12 )CH), 73.81 )CHCl2), 115.15
)CH), 115.66 )CH), 127.17 )CH), 128.79 )CH), 132.30
)CH), 133.20)C), 137.95 )C), 153.75 )C), 167.58 )CO);
MS m/z )%): 338 )M1, 5), 256 )6), 181 )5), 147 )4), 134
)40), 123 )58), 108 )46), 105 )100), 77 )80); IR )Nujol):
3339, 1634, 1506, 1484, 1379, 1251, 1041, 829, 790,
3.3.11. N-ꢀ1-Benzylamino-2,2-dichloroethyl)-3,4,5-tri-
methoxybenzamide ꢀ4k). )74%), white needles )pet
ether±dichloromethane) mp 145±1488C. )Found: C 55.48;
H 5.43; N 6.58; C19H22Cl2N2O4 requires: C 55.22; H 5.37; N
6.78); 1H NMR d )CDCl3, 200 MHz): 2.31 )s, 1H), 3.89 )s,
2H), 3.90)s, 6H), 3.96 )s, 3H), 5.35 )dd, 1H, Jˆ9.0, 2.5 Hz),
6.03 )d, 1H, Jˆ2.7 Hz), 6.54 )d, 1H, Jˆ8.4 Hz), 6.99 )s,
2H), 7.27±7.35 )m, 5H); 13C NMR d )CDCl3, 50.4 MHz):
50.62 )CH2), 56.46 )CH3O), 60.98 )CH3O), 69.04 )CH),
74.43 )CHCl2), 104.71 )CH), 127.51 )CH), 128.18 )CH),
128.66 )CH), 128.78 )C), 139.17 )C), 153.36 )C), 167.31
)CO); MS m/z )%): 211 )4), 196 )3), 140)4), 118 )8), 91
)100), 77 )5); IR )Nujol): 3290, 1631, 1582, 1497, 1471,
1356, 1237, 1132, 998, 847 cm21
.
722 cm21
.
3.3.12. N-ꢀ2,2-Dichloro-1-dimethylaminoethyl)-2-methyl-
benzamide ꢀ4l). )80%), white needles )hexane) mp 1128C.
)Found: C 52.44; H 5.92; N 9.98; C12H16Cl2N2O requires: C
3.3.16. N-ꢀ1-Amino-2,2-dichloroethyl)benzamide ꢀ4p).
)67%), white needles )ethyl acetate±hexane) mp 82±858C.
)Found: C 45.97; H 4.77; N 12.02; C9H11Cl2N2O requires: C
1
1
52.38; H 5.86; N 10.18); H NMR d )CDCl3, 200 MHz):
46.18; H 4.74; N 11.97); H NMR d )CDCl3, 200 MHz):
2.45 )s, 6H), 2.49 )s, 3H), 5.20)dd, 1H, Jˆ9.6 Hz, Jˆ
3.6 Hz), 5.99 )d, 1H, Jˆ3.7 Hz), 6.38 )d, 1H, Jˆ8.5 Hz),
7.21±7.48 )m, 4H); 13C NMR d )CDCl3, 50.4 MHz): 20.09
)CH3), 41.56 )CH3), 73.14 )CH), 73.68 )CHCl2), 125.98
)CH), 126.74 )CH), 130.51 )CH), 131.30 )CH), 135.66
)C), 136.39 )C), 170.49 )CO); MS m/z )%): 191 )M12
2.13 )br s, 2H), 5.33 )dd, 1H, Jˆ7.0, 1.8 Hz), 6.10 )d, 1H,
Jˆ1.8 Hz), 6.78 )d, 1H, Jˆ5.5 Hz), 7.41±7.54 )m, 3H), 7.78
)d, 2H, Jˆ7.7 Hz); 13C NMR d )CDCl3, 50.4 MHz): 64.80
)CH), 75.31 )CHCl2), 127.12 )CH), 128.78 )CH), 132.22
)CH), 133.42 )C), 167.20)CO); MS m/z )%): 217 )2), 215
)3), 180 )2), 121 )2), 105 )100), 77 )58); IR )Nujol): 3407,

5092
A. Guirado et al. / Tetrahedron 58 /2002) 5087±5092
3315, 1633, 1522, 1489, 1460, 1380, 1307, 1076, 1045, 933,
789, 720cm 21
300 MHz): 2.29 )s, 2H), 5.76 )d, 1H, Jˆ9.3 Hz), 6.71 )d,
1H, Jˆ8.7 Hz), 7.43±7.55 )m, 3H), 7.78±7.81 )m, 2H); 13C
NMR d )CDCl3, 75.4 MHz): 70.60 )CH), 103.38 )CCl3),
127.26 )CH), 128.85 )CH), 132.37 )CH), 133.49 )C),
166.96 )CO); MS m/z )%): 230)M 12HCl, 1), 195 )2),
149 )21), 105 )100), 77 )52); i.r.: 3370, 3290, 1651, 1553,
.
3.4. Preparation of N-ꢀarylamino-2,2,2-trichloroethyl)-
benzamides 5n,o and N-ꢀamino-2,2,2-trichloroethyl)-
benzamide 5p
1377, 1334, 827, 794, 710cm 21
.
Products 5n,o were prepared by reaction of 2a with the
corresponding amines: To a well-stirred solution of 2a
)7 mmol) in dry acetone )5 mL) at room temperature, a
solution of the arylamine )7 mmol) and triethylamine
)7 mmol) in dry acetone )10mL) was added dropwise. An
almost instantaneous formation of a precipitate of triethyl-
amine hydrochloride was observed upon addition of the ®rst
drops. This solid was removed by ®ltering and the solvent
was removed under reduced pressure, leaving an oily resi-
due, which was shaken with petroleum ether. The white
solid formed was collected by ®ltration and crystallized
from the appropriate solvent.
3.5. X-Ray crystallographic analysis of N-ꢀ2,2-dichloro-
1-isopentylaminoethyl)-4-methylbenzamide ꢀ4m)
Crystal data: C15H22Cl2N2O, Mrˆ317.25, monoclinic,
Ê
P2)1)/c, aˆ10.7446)7), bˆ9.0414)5), cˆ17.8914)10) A,
Ê 3
bˆ106.440 )10)8, Vˆ1667.0)2) A , Zˆ4, l )Mo Ka)ˆ
Ê
0.71073 A, Tˆ21008C. Data collection: colorless block
0.60£0.34£0.32 mm3, Siemmens P4 diffractometer, 4361
intensities )2932 unique), 2umax 508. Structure solution
and re®nement: direct methods, re®ned on F2 )program
È
SHELXL-93, G. M. Sheldrick, University of Gottingen),
H atoms with riding model except H01 and H02 free, wR
)F2) 0.0996, R )F) 0.036, 189 parameters, Sˆ1.099, max.
Product 5p was prepared by reaction of 2a with ammonia in
a two-phase system )Et2O±NH3 aq). A solution of 2a
)10mmol) in ether )30mL) was added dropwise at room
temperature to a vigorously stirred solution of ammonium
hydroxide )30%) in water )25 mL), stirring was continued
for 10min. Then the organic layer was dried on anhydrous
magnesium sulphate. Evaporation of ether gave a white
solid residue which was crystallized from hexane/dichloro-
methane.
Ê 23
Dr 0.335 e A
.
Complete crystallographic data )excluding structure factors)
have been deposited at the Cambridge Crystallographic Data
Centre under the reference numbers CCDC 178736. Copies
of the data can be obtained free of charge, on application to
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax:
144)0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
3.4.1. N-ꢀ2,2,2-Trichloro-1-phenylaminoethyl)benzamide
ꢀ5n). )96%), white needles )hexane±dichloromethane) mp
Acknowledgements
172±1748C. )Found:
C
52.58;
H
3.79;
N
8.22;
C15H13Cl3N2O requires: C 52.43; H 3.81; N 8.15); 1H
NMR d )CDCl3, 200 MHz): 4.57 )br s, 1H), 6.41 )d, 1H,
Jˆ9.2 Hz), 6.74 )d, 1H, Jˆ9.1 Hz), 6.80±6.87 )m, 3H),
7.17±7.26 )m, 2H), 7.37±7.57 )m, 3H), 7.75±7.80)m,
2H); 13C NMR d )CDCl3, 50.4 MHz): 70.94 )CH), 101.43
)CCl3), 114.46 )CH), 120.11 )CH), 127.28 )CH), 128.84
)CH), 129.72 )CH), 132.42 )CH), 133.24 )C), 144.02 )C),
167.44 )CO); MS m/z )%): 344 )1), 342 )M1, 1), 271 )1),
225 )18), 167 )1), 151 )1), 122 )21), 105 )100), 93 )17), 77
)80); IR )Nujol): 3367, 3280, 1646, 1603, 1530, 1504, 1344,
We gratefully acknowledge the ®nancial support of the
Â
Ministerio de Ciencia y Tecnologõa )project BQU2000-0222).
References
1. Meldrum, A. N.; Bhojraj, M. G. J. Indian Chem. Soc. 1936,
13, 185±186.
Â
2. Guirado, A.; Andreu, R.; Cerezo, A.; Galvez, J. Tetrahedron
2001, 39, 4925±4931.
3. Guirado, A.; Andreu, R.; Galvez, J. Tetrahedron Lett. 1998,
1300, 1078, 1032, 885, 776, 745 cm21
.
Â
39, 1071±1074.
4. Guirado, A.; Andreu, R.; Galvez, J. Tetrahedron Lett. 1999,
Â
3.4.2. N-[2,2,2-Trichloro-1-ꢀ4-methoxyphenylamino)-
40, 8163±8165.
5. Rappoport, Z. In The Chemistry of Alkenes, Patai, S., Ed.;
Wiley-Interscience: London, 1964 Chapter 8.
ethyl]benzamide ꢀ5o). )97%), white needles )hexane±
dichloromethane) mp 170±1718C. )Found: C 51.46; H
3.98; N 7.46; C16H15Cl3N2O2 requires: C 51.43; H 4.05; N
7.50); 1H NMR d )CDCl3, 200 MHz): 3.71 )s, 3H), 6.29 )d,
1H, Jˆ9.5 Hz), 6.77 )br s, 5H), 7.38±7.50)m, 3H), 7.73±
7.77 )m, 2H); 13C NMR d )CDCl3, 50.4 MHz): 55.69
)CH3O), 71.98 )CH), 102.00 )CCl3), 115.12 )CH), 115.91
)CH), 127.24 )CH), 128.81 )CH), 132.36 )CH), 133.27 )C),
137.86 )C), 153.84 )C), 167.55 )CO); MS m/z )%):372 )M1,
1), 255 )10), 216 )1), 181 )2), 166 )2), 152 )6), 134 )35), 122
)24), 105 )100), 77 )67); IR )Nujol): 3373, 3218, 1643, 1547,
6. Rappoport, Z. In Advances in Physical Organic Chemistry,
Gold, V., Ed.; Academic: London, 1969 Chapter 1.
7. )a) Rappoport, Z. Recl. Trav. Chim. Pays-Bas 1985, 104, 30 9±
349. )b) Shainyan, B. A. Russ. Chem. Rev. 1986, 55, 511±530.
8. Patrick, G. L. Comprehensive Organic Functional Group
Transformations; Kirby, G. W., Ed.; Pergamon: Oxford,
1995; Vol. 4, p. 970.
9. Gasc, M. B.; Lattes, A.; Perie, J. J. Tetrahedron 1983, 39,
703±731.
1512, 1375, 1286, 1236, 1149, 1037, 814, 796, 720 cm21
.
10. Caution must be exercised when handling perchlorates in
order to exclude explosion risk. Evaporation of organic solu-
tions containing perchlorates requires to be carried out in
vacuo and at moderate temperature. The contact with strong
acids must be avoided.
3.4.3. N-ꢀ1-Amino-2,2,2-trichloroethyl)benzamide ꢀ5p).
)75%), white needles )hexane±dichloromethane) mp 96±
998C. )Found: C 40.29; H 3.43; N 10.41; C9H9Cl3N2O
1
requires: C 40.40; H 3.39; N 10.47); H NMR d )CDCl3,