N-Alkylation of anilines, carboxamides and several nitrogen heterocycles using CsF-Celite/alkyl halides/CH3CN combination

Article abstract of DOI:10.1016/S0040-4020(01)00989-9

It has been found that the N-alkylation of aniline, carboxamides and heterocyclic compounds bearing an acidic hydrogen atom attached to nitrogen can be accomplished with alkyl halides in acetonitrile and cesium fluoride-celite employed as a solid base. In this manner, pyrrole, indole, pyrazole, imidazole, benzimidazole, carbazole, phthalimide, indazole, indoline, 2-pyrrolidinone, piperidine and 1,2,4-triazole can be successfully alkylated. The procedure is convenient, efficient and generally gives rise to the N-alkylated product exclusively.

Full text of DOI:10.1016/S0040-4020(01)00989-9

TETRAHEDRON
Pergamon
Tetrahedron 57 ꢀ2001) 9951±9957
N-Alkylation of anilines, carboxamides and several nitrogen
heterocycles using CsF±Celite/alkyl halides/CH CN combination
3
a
Safdar Hayat, Atta-ur-Rahman, M. Iqbal Choudhary, Khalid Mohammed Khan,
a
a
a
b
Wilhelm Schumann and Ernst Bayer
b,p
a
H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan
b
Institut f uÈ r Organische Chemie, Universit aÈ t T uÈ bingen, Auf der Morgenstelle 18, D-72076 T uÈ bingen, Germany
Received 9 August 2001; revised 1 October 2001; accepted 10 October 2001
AbstractÐIt has been found that the N-alkylation of aniline, carboxamides and heterocyclic compounds bearing an acidic hydrogen atom
attached to nitrogen can be accomplished with alkyl halides in acetonitrile and cesium ¯uoride±celite employed as a solid base. In this
manner, pyrrole, indole, pyrazole, imidazole, benzimidazole, carbazole, phthalimide, indazole, indoline, 2-pyrrolidinone, piperidine and
1,2,4-triazole can be successfully alkylated. The procedure is convenient, ef®cient and generally gives rise to the N-alkylated product
exclusively. q 2001 Published by Elsevier Science Ltd.
1
3
1
. Introduction
focused on reductive N-alkylation, where aldehydes or
ketones react with amine in the presence of hydrogen and
a catalyst to yield N-alkylation amines. N-Alkylation of
carboxamides is not only important for the selective
The importance of the ¯uoride ion as a catalyst for the
promotion of various types of base-catalyzed reactions in
organic synthesis has been previously recognized. The
1
14
synthesis of secondary and tertiary amines, but also essen-
tial for the preparation of a number of pharmaceuticals.
2
15
work of Clark and Miller, in particular, revealed that the
¯
uoride ion has an effect on condensation reactions because
2
of its high capability of hydrogen-bond formation. As
reagents generating ¯uoride ion in these reactions,
potassium, cesium and tetraalkylammonium ¯uorides are
generally used so far. However, it is not easy to handle
these hygroscopic reagents and the reproducibility of the
reactions is invariably poor. Previously, poorly hygroscopic
reagents generating a ¯uoride ion were designed by allow-
N-Alkylation of secondary amines with alkyl halides is an
important synthetic method to obtain tertiary amines.
However, quaternary salt formation results in lower yields
of the tertiary amines. Generally a large excess of the
1
6
secondary amine is used to control this. Strong bases
1
7
18
such as lithium naphthalenide, Et N and KH, KOH in
3
1
acetone and in DMSO, potassium, sodium amide,
9
20
21
3
22
sodium hydroxide in hexamethylphosphoric triamide and
ing cesium ¯uoride to be absorbed on a Celite. Although
2
3
this reagent is effective in some reactions, reproducibility of
the preparation of the reagent is not so good and reactions
result in different yields in our experiments.
thalliumꢀI) ethoxide have been used. Furthermore, a few
investigations of N-alkylation of aromatic compounds
involving nitrogen heterocycles with alkyl halide under
2
4
phase transfer catalytic conditions have been reported. In
many cases, KOH and t-BuOK were employed as a base in
the presence of crown ethers as phase transfer catalysts
4
±6
Many reports have been published for N-mono- and N,N-
di-alkylation of aniline. Moreover, N-alkylation of aniline
with methanol can be achieved by various catalysts such as
2
5
26
ꢀPTC). On the other hand, Sukata reported the N-alkyl-
ation of nitrogen heterocycles using aqueous or powdered
potassium hydroxide as a base in the presence of poly-
ethylene glycols ꢀPEG) or their dialkyl ethers ꢀPEG±
ether) as phase transfer catalysts. Recently, several reports
on N-alkylation of nitrogen heterocycles with alkyl halide
7
8
9
alumina, MgO and NaOH/Al O and ruthenium complex.
2
3
1
0
Bergman et al. reported aniline alkylation with oxalic
esters by use of various bases such as Na CO and
t-BuOK. Anilines are selectively monoalkylated over alkali
cation exchanged X and Y zeolites in a solvent. Amines
are alkylated ef®ciently using mixed alkylarylbismuth and
catalysis by a copper reagent. Much attention has been
2
3
1
1
absorbed on K
and benzotriazole in basic media and azoles in dry media
CO , aza heterocycles in dry media, triazole
3
2
1
2
2
7
have appeared. N-alkylation of arylpiperazines and of
2
8
aniline has also been reported under MW irradiation.
Keywords: aniline; carboxamides; nitrogen heterocycles; cesium ¯uoride±
celite.
Corresponding author. Tel.: 149-7071-297-2437; fax: 149-7071-297-
5034; e-mail: ernst.bayer@uni-tuebingen.de
p
In this communication, a convenient and ef®cient method
for N-alkylation of anilines, carboxamides and aromatic
0040±4020/01/$ - see front matter q 2001 Published by Elsevier Science Ltd.
PII: S0040-4020ꢀ01)00989-9

9952
S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
Table 1. N-Mono- and N,N-di-alkylation of anilines using CsF±Celite in
CH CN
reaction of aniline ꢀ1a) with benzyl bromide in place of
benzyl chloride produced 3a as the major product ꢀentry
2). The reaction of aniline ꢀ1a) with low boiling alkyl
halides such as ethyl bromide and methyl iodide resulted
in formation of corresponding N-ethylaniline ꢀ2a-I) and
N,N-diethylaniline ꢀ3a-I) and N-methylaniline ꢀ2a-II) and
N,N-dimethylaniline ꢀ3a-II) products in somewhat lower
yields ꢀentries 3 and 4), respectively. In addition, 4-nitro-
aniline ꢀ1b) was converted with benzyl chloride and
3
a
b
Yield ꢀ%)
Entry
Substrate
Alkyl halide
Product
1
2
3
4
5
6
7
8
1a
±
±
±
1b
±
A
B±
C
D
A
B±
A
B±
2a/3a
21/58
2a-I/3a-I
2a-II/3a-II
2b/3b
32/57
2c/3c
35/54
22/72
10/19
12/21
36/64
1c
±
45/50
-bromide into N-benzyl-4-nitroaniline ꢀ2b) and N,N-
dibenzyl-4-nitroaniline ꢀ3b) in satisfactory yields ꢀentries
5 and 6). 4-Aminobenzophenone ꢀ1c) was also reacted
with benzyl chloride and -bromide using CsF±Celite in
acetonitrile to form the corresponding N-benzyl-4-amino-
benzophenone ꢀ2c) and N,N-dibenzyl-4-aminobenzo-
phenone ꢀ3c) products by this procedure in satisfactory
yields ꢀentries 7 and 8) ꢀScheme 1).
a
A: PhCH Cl, B: PhCH
2
Isolated yields of pure products.
2 2 5 3
Br, C: C H Br, D: CH I.
b
compounds involving nitrogen heterocycles using
cesium ¯uoride±celite as a solid base in acetonitrile is
described.
On the basis of these results, a diphenylamine ꢀ4) and a
variety of carboxamides were allowed to react with alkyl
halides using CsF±Celite as a solid base in CH CN under
3
re¯ux ꢀTable 2). Diphenylamine ꢀ4) and acetanilide ꢀ5) were
reacted with benzyl chloride using CsF±Celite in aceto-
nitrile to form the corresponding N-benzyldiphenylamine
ꢀ4a) and N-benzylacetanilide ꢀ5a) products in good yields
ꢀentries 1 and 2). Similarly, formanilide ꢀ6) was converted
The chemistry of the CsF±Celite has been studied because it
can serve as an excellent base for converting carboxylic
acids into their corresponding esters with alkyl halides.
3
Alkylation of cesium carboxylate salts with alkyl halides
is also a very useful tool for the preparation of carboxylic
1
a,b,29
esters.
In the course of our study to extend the scope of
the CsF±Celite in organic synthesis, we have found that
with alkyl halides, aniline, carboxamides and nitrogen
heterocycles are converted to the corresponding N-alkylated
products in good yield using CsF±Celite as a solid base in
with CH I into N-methylformanilide ꢀ6a) in somewhat
3
lower yield ꢀ41%) ꢀentry 3). The reaction of benzamide
ꢀ7) with an alkylating agent such as benzyl chloride and
-bromide resulted in formation of N-benzylbenzamide ꢀ7a)
and N,N-dibenzylbenzamide ꢀ7b), but with unsatisfactory
yields ꢀentries 4 and 5).
the presence of CH CN.
3
2
. Results and discussion
Table 3 shows the N-alkylation of several nitrogen hetero-
cycles using CsF±Celite as a base ꢀmolar ratio: CsF±Celite/
heterocycleˆ1.5/1.0). When the alkylating agents such as
benzyl chloride and -bromide were employed, the N-benzyl-
ated products were obtained in very good yields ꢀentries 1,
2, 4, 5, 7, 8 and 10±23). However, the yield of the N-benzyl-
1-2-4-triazole ꢀ18a) was generally low ꢀentries 24 and 25).
On the other hand, the alkylation of nitrogen heterocycles
with isopropyl iodide, ethyl iodide and -bromide gave
N-alkylated products in lower yields ꢀentries 3, 9, 26 and
27). Similarly, the reaction of imidazole ꢀ9) with vinyl
bromide gave N-vinylimidazole ꢀ9b) product in satisfactory
yield ꢀentry 6).
The CsF±Celite assisted coupling of substituted anilines
with various alkyl halides, resulted in N-mono- and N,N-
di-alkylation ꢀTable 1). A typical reaction is described as
follows. A mixture of aniline ꢀ1a) ꢀ1.0 mmol), CsF±Celite
ꢀ
1.5 mmol) and benzyl chloride ꢀ2.0 mmol) in acetonitrile
was stirred under re¯ux for 2 days. The reaction produced
N,N-dibenzylaniline ꢀ3a) in 72% yield along with N-benzyl-
aniline ꢀ2a) ꢀ22%) ꢀentry 1). When aniline ꢀ1a) and benzyl
chloride were allowed to react with a stoichiometric amount
ꢀ
1 equiv.), 2a was formed in satisfactory yield ꢀ64%).
Hence, the reaction was carried out by the use of
:2 equiv. of aniline ꢀ1a)/benzyl chloride. Similarly, the
1
Scheme 1.

S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
Table 2. N-Mono- and N,N-di-alkylation of carboxamides and diphenylamine using CsF±Celite in CH
9953
3
CN
a
b
Product ꢀyield %)
Entry
Substrate
Alkyl halide
N-Alkylation
N,N-Dialkylation
1
2
3
4
5
ꢀC
CH
HCONHC
6
H
5
)
2
NH ꢀ4)
A
A
D
4a ꢀ70)
5a ꢀ65)
6a ꢀ41)
7a ꢀ32)
± ꢀ49)
3
CONHC
6
H
5
ꢀ5)
ꢀ6)
ꢀ7)
6
H
5
C
±
6
H
5
CONH
2
A
B± ꢀ30)
7b ꢀ60)
a
A: PhCH
Isolated yields of pure products.
2
Cl, B: PhCH
2 3
Br, D: CH I.
b
Table 3. N-Alkylation of nitrogen heterocyclic compounds using CsF±Celite in CH
3
CN
a
b
Yield ꢀ%)
Entry
Substrate
Alkyl halide
Product
1
2
3
4
5
6
7
8
9
Phthalimide ꢀ8)
±
±
Imidazole ꢀ9)
A
B
E
A
B
F
A
B
E
A
B±
A
B±
A
B±
A
B±
A
B±
A
B±
A
N-Benzylphthalimide ꢀ8a)
95
±
±
±
86
79
90
N-Isopropylphthalimide ꢀ8b)
N-Benzylimidazole ꢀ9a)
51
92
±
±
Benzimidazole ꢀ10)
±
±
Indole ꢀ11)
±
Pyrrole ꢀ12)
±
Pyrazole ꢀ13)
±
Indazole ꢀ14)
±
Indoline ꢀ15)
±
Carbazole ꢀ16)
±
2-Pyrrolidinone ꢀ17)
±
1,2,4-Triazole ꢀ18)
±
Piperidine ꢀ19)
±
N-Vinylimidazole ꢀ9b)
N-Benzylbenzimidazole ꢀ10a)
66
94
N-Isopropylbenzimidazole ꢀ10b)
N-Benzylindole ꢀ11a)
82
48
92
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
N-Benzylpyrrole ꢀ12a)
91
96
90
98
93
90
44
78
N-Benzylpyrazole ꢀ13a)
82
N-Benzylindazole ꢀ14a)
81
N-Benzylindoline ꢀ15a)
88
N-Benzylcarbazole ꢀ16a)
81
N-Benzyl-2-pyrrolidinone ꢀ17a)
78
N-Benzyl-1-2-4-triazole ꢀ18a)
32
B±
A
B±
G
N-Ethylpiperidine ꢀ19a)
±
42
35
C
a
A: PhCH
Isolated yields of pure products.
2
Cl, B: PhCH
2 2 5 4 9 2 2 5
Br, C: C H Br, E: i-C H I, F: CH vCHBr, G: C H I.
b
The method presented is generally being equally applicable
to aniline, carboxamides and nitrogen heterocyclic
compounds and provides the corresponding N-alkylated
products in very good to acceptable yields. Products
obtained were quite pure in most cases with no C-alkylation
or quaternary salt formation being detected.
apparatus and are uncorrected. The ultraviolet spectra
were measured in chloroform on a Lambda 5 UV/VIS spec-
trometer ꢀPerkin±Elmer). IR spectra ꢀKBr discs) were
recorded on a Bruker FT-IR IFS 48 spectrometer. EI mass
spectral data were recorded with Varian MAT 711 ꢀ70 ev)
1
spectrometer, and data are tabulated as m/z. H NMR and
1
3
C NMR spectra were recorded in CDCl containing ca. 1%
3
In conclusion, the CsF±Celite/alkyl halide/CH CN combi-
3
tetramethylsilane as an internal standard a Brucker AC 250
ꢀ250 MHz and 62.9 MHz) spectrometer, respectively.
Chemical shifts are reported in d ꢀPPM) and coupling
constants are given in Hz. The progress of all reactions
was monitored by TLC on 2.0£5.0 cm aluminum sheets
precoated with silica gel 60F to a thickness of 0.25 mm
nation provides a clean, ef®cient and convenient method for
the N-alkylation of aniline, carboxamides and other
N-heterocycles in very good yields. Although it is less reac-
tive than potassium and tetraalkylammonium ¯uorides, it is
superior in terms of ease of handling and economy.
2
54
ꢀMerck). The chromatograms were visualized under ultra-
violet light ꢀ254±366 nm).
3
. Experimental
3.2. Materials
3
.1. General
Aniline, 4-nitroaniline, diphenylamine, 4-aminobenzo-
phenone, benzamide, acetanilide, formanilide and all
Melting points were determined with a B uÈ chi SMP-20

9954
S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
nitrogen heterocyclic compounds together with the reagent
alkyl halides, CsF and Celite 521 are commercially avail-
able ꢀFluka, Aldrich), while anhydrous acetonitrile was
purchased from Merck and used without puri®cation. The
CsF±Celite was prepared by stirring an aqueous solution of
197 ꢀ43), 149 ꢀ11), 125 ꢀ19), 108 ꢀ25), 91 ꢀ57), 77 ꢀ9), 57
ꢀ11), 45 ꢀ100). Anal. calcd for C H NO: C, 83.60; H, 5.96;
N, 4.87. Found: C, 83.52; H, 5.88; N, 4.93.
2
0
17
3.3.4. N,N-Dibenzyl-4-aminobenzophenone ꢀ3c). Yield:
190 mg ꢀ50%). Colorless compound. Mp 91±938C.
3
CsF with Celite 521 at room temperature for 20 min.
R ˆ0.58 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr): 3052,
f
2
7
940, 2875, 1715, 1645, 1448, 1156, 1038, 784,
35 cm . H NMR ꢀ250 MHz, CDCl ): d 7.73 ꢀd, 2H,
3
.3. Typical procedure for N-alkylation
2
1
1
3
Jˆ7.5 Hz, Ar-H), 7.68±7.19 ꢀm, 15H, Ar-H), 6.74 ꢀd, 2H,
To a stirred solution of nitrogen compounds ꢀ1.0 mmol) and
CsF±Celite ꢀ1.5 mmol) in 100 ml of acetonitrile, alkyl
halide ꢀ2.0 mmol) was added. After stirring at re¯ux for
two days, the solvent was evaporated and the residue was
dissolved in ethyl acetate. The precipitates were ®ltered off,
washed with ethyl acetate ꢀ20 ml) and ®ltrate was evapo-
rated under reduced pressure. The product was puri®ed
wherever necessary by column chromatography on silica
gel using hexane/ethyl acetate ꢀ9:1, v/v) as an eluent to
afford pure N-alkylated product.
1
3
Jˆ7.5 Hz, Ar-H), 4.71 ꢀs, 4H, benzyl-CH ). C NMR
2
ꢀ63 MHz, CDCl ): d 194.9, 152.6, 139.2, 137.3, 137.3,
3
1
1
1
3
32.9, 132.9, 131.2, 129.4, 129.4, 128.9, 128.9, 128.9,
28.9, 128.0, 128.0, 127.4, 127.4, 126.5, 126.5, 126.5,
26.5, 125.8, 111.3, 111.3, 54.2, 54.2. EI MS ꢀm/z, %):
1
77 ꢀM , 48), 300 ꢀ43), 286 ꢀ52), 208 ꢀ62), 181 ꢀ32), 152
ꢀ27), 105 ꢀ12), 91 ꢀ100), 77 ꢀ9), 65 ꢀ13), 43 ꢀ5). Anal. calcd
for C H NO: C, 85.91; H, 6.14; N, 3.71. Found: C, 85.98;
H, 6.08; N, 3.78.
27 23
3
.3.5. N-Benzyldiphenylamine ꢀ4a). Yield: 180 mg ꢀ70%).
The physical properties and NMR spectra of 2a, 3a, 2a-I,
3
reported in the literatures and were identi®ed by compar-
ing with those of authentic samples.
Oily compound. R ˆ0.44 ꢀhexane/ethyl acetate, 5:1). IR
a-I, 2a-II and 3a-II were in good agreement with those
f
3
0
ꢀCHCl ): 3056, 2942, 2854, 1642, 1484, 1254, 1044, 964,
3
2
1 1
62, 745 cm . H NMR ꢀ250 MHz, CDCl ): d 7.53±7.22
7
3
ꢀm, 5H, Ar-H), 7.21±6.88 ꢀm, 10H, Ar-H), 4.98 ꢀs, 2H,
1
3
benzyl-CH2). C NMR ꢀ63 MHz, CDCl ): d 148.1, 148.1,
3
.3.1. N-Benzyl-4-nitroaniline ꢀ2b). Yield: 80 mg ꢀ36%).
3
1
1
5
1
39.2, 129.3, 129.3, 129.3, 129.3, 128.5, 128.5, 126.7,
Yellow color. Mp 72±748C. R ˆ0.33 ꢀhexane/ethyl acetate,
f
26.5, 126.5, 121.3, 121.3, 120.7, 120.7, 120.7, 120.7,
6.3. EI MS ꢀm/z, %): 259 ꢀM , 85), 182 ꢀ63), 169 ꢀ54),
49 ꢀ32), 101 ꢀ52), 91 ꢀ100), 77 ꢀ11), 65 ꢀ10), 57 ꢀ9), 45 ꢀ8).
5
1
8
6
:2). IR ꢀKBr): 3372, 2958, 2854, 1645, 1551, 1524, 1408,
1
2
245, 1035, 786, 738 cm . H NMR ꢀ250 MHz, CDCl ): d
1 1
3
.04 ꢀd, 2H, Jˆ7.2 Hz, Ar-H), 7.41±7.25 ꢀm, 5H, Ar-H),
Anal. calcd for C H N: C, 87.99; H, 6.61; N, 5.40. Found:
19 17
C, 87.89; H, 6.72; N, 5.37.
.57 ꢀd, 2H, Jˆ7.2 Hz, Ar-H), 4.96 ꢀbr, s, 1H, N±H), 4.43
1
3
ꢀ
s, 2H, benzyl-CH ). C NMR ꢀ63 MHz, CDCl ): d 153.1,
2
3
1
1
1
38.4, 137.4, 128.9, 128.9, 127.8, 127.3, 127.3, 126.4,
26.4, 111.3, 111.3, 47.7. EI MS ꢀm/z, %): 228 ꢀM , 47),
81 ꢀ44), 151 ꢀ37), 105 ꢀ22), 91 ꢀ100), 83 ꢀ15), 65 ꢀ11), 57
3
.3.6. N-Benzylacetanilide ꢀ5a) . Yield: 150 mg ꢀ65%).
0
1
3
Oily compound. R ˆ0.45 ꢀhexane/ethyl acetate, 5:2). IR
f
ꢀ
CHCl ): 3072, 2956, 2862, 1684, 1656, 1416, 1235,
3
ꢀ9). Anal. calcd for C H N O : C, 68.41; H, 5.30; N, 12.27.
Found: C, 68.49; H, 5.24; N, 12.36.
1
3
12
2
2
2
058, 784, 738 cm . H NMR ꢀ250 MHz, CDCl ): d
1
1
1
3
7
.36±7.28 ꢀm, 8H, Ar-H), 7.26±7.20 ꢀm, 2H, Ar-H), 4.54
1
3
3
.3.2. N,N-Dibenzyl-4-nitroaniline ꢀ3b). Yield: 200 mg
ꢀs, 2H, benzyl-CH ), 2.94 ꢀs, 3H, CH ). C NMR ꢀ63 MHz,
2 3
ꢀ
acetate, 5:2). IR ꢀKBr): 3016, 2934, 2856, 1642, 1548, 1208,
64%). Yellow color. Mp 84±868C. R ˆ0.53 ꢀhexane/ethyl
2
046, 784, 742 cm . H NMR ꢀ250 MHz, CDCl ): d 8.06
CDCl ): d 166.5, 141.0, 137.4, 129.6, 128.8, 128.8, 128.5,
3
f
128.2, 128.2, 127.5, 127.5, 127.1, 127.1, 65.1, 22.6. EI MS
ꢀm/z, %): 225 ꢀM , 21), 182 ꢀ61), 167 ꢀ52), 108 ꢀ32), 91
1
1
1
1
3
ꢀ
d, 2H, Jˆ7.4 Hz, Ar-H), 7.40±7.06 ꢀm, 10H, Ar-H), 6.67
ꢀ48), 79 ꢀ100), 77 ꢀ10), 51 ꢀ9). Anal. calcd for C15H15NO: C,
79.97; H, 6.71; N, 6.22. Found: C, 79.86; H, 6.79; N, 6.18.
1
3
C
ꢀ
NMR ꢀ63 MHz, CDCl ): d 153.8, 137.9, 136.4, 136.4,
d, 2H, Jˆ7.4 Hz, Ar-H), 4.76 ꢀs, 4H, benzyl-CH ).
2
3
1
1
29.0, 129.0, 129.0, 129.0, 127.6, 127.6, 126.3, 126.3,
26.3, 126.3, 126.2, 126.2, 111.2, 111.2, 54.4, 54.4. EI
3.3.7. N-Methylformanilide ꢀ6a). Yield: 60 mg ꢀ41%).
Oily compound. R
ꢀCHCl ): 3384, 2932, 2774, 1689, 1658, 1408, 1242, 768,
ˆ0.34 ꢀhexane/ethyl acetate, 5:2). IR
f
1
MS ꢀm/z, %): 318 ꢀM , 15), 237 ꢀ21), 227 ꢀ25), 180 ꢀ14),
3
2
1
1
745 cm . H NMR ꢀ250 MHz, CDCl ): d 8.28 ꢀs, 1H,
149 ꢀ18), 105 ꢀ46), 91 ꢀ100), 77 ꢀ7), 65 ꢀ5), 51 ꢀ13), 43 ꢀ9).
Anal. calcd for C H N O : C, 75.45; H, 5.70; N, 8.80.
Found: C, 75.56; H, 5.62; N, 8.91.
3
±COH), 7.25 ꢀdd, 2H, Jˆ8.2, 1.7 Hz, Ar-H), 7.09 ꢀdd, 2H,
Jˆ8.2, 8.2 Hz, Ar-H), 6.97 ꢀdd, 1H, Jˆ8.2, 1.7 Hz, Ar-H),
2
0
18
2
2
1
3
3.09 ꢀs, 3H, N±CH ). C NMR ꢀ63 MHz, CDCl ): d 161.9,
142.0, 129.4, 129.4, 125.8, 121.7, 121.7, 31.4. EI MS ꢀm/z,
3
3
3
1
.3.3. N-Benzyl-4-aminobenzophenone ꢀ2c). Yield:
30 mg ꢀ45%). Colorless compound. Mp 105±1078C.
1
%): 135 ꢀM , 100), 107 ꢀ63), 91 ꢀ52), 77 ꢀ21), 66 ꢀ16), 51
R ˆ0.33 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr): 3348,
ꢀ9). Anal. calcd for C H NO: C, 71.09; H, 6.71; N, 10.36.
8 9
Found: C, 70.98; H, 6.76; N, 10.29.
f
2
7
1
962, 2845, 1716, 1642, 1416, 1232, 1032, 784,
2
36 cm . H NMR ꢀ250 MHz, CDCl ): d 7.62±7.24 ꢀm,
1 1
3
0H, Ar-H), 7.69 ꢀd, 2H, Jˆ7.6 Hz, Ar-H), 6.57 ꢀd, 2H,
3.3.8. N-Benzylbenzamide ꢀ7a). Yield: 70 mg ꢀ32%).
Jˆ7.6 Hz, Ar-H), 4.65 ꢀs, 1H, N±H), 4.37 ꢀs, 2H, benzyl-
Colorless compound. Mp 103±1058C. R ˆ0.69 ꢀhexane/
f
1
3
CH ). C NMR ꢀ63 MHz, CDCl ): d 195.3, 152.1, 139.2,
ethyl acetate, 5:2). IR ꢀKBr): 3425, 3015, 2916, 2826,
2
3
2
1
1
1
1
4
38.4, 133.0, 133.0, 131.2, 129.5, 129.5, 128.5, 128.5,
28.0, 127.5, 127.5, 127.3, 127.3, 126.3, 111.6, 111.6,
7.6. EI MS ꢀm/z, %): 287 ꢀM , 43), 223 ꢀ21), 210 ꢀ32),
1688, 1485, 1252, 1048, 785, 734 cm . H NMR
ꢀ250 MHz, CDCl ): d 7.36±7.28 ꢀm, 5H, Ar-H), 7.26±
7.20 ꢀm, 5H, Ar-H), 4.55 ꢀs, 2H, benzyl-CH ), 2.94 ꢀbr, s,
3
1
2

S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
9955
1
H, N±H). C NMR ꢀ63 MHz, CDCl ): d 166.5, 141.0,
3
1
1
1
1
ꢀCHCl ): 3015, 2954, 2818, 2162, 1645, 1432, 1064, 985,
3
3
21 1
764, 732 cm . H NMR ꢀ250 MHz, CDCl ): d 7.52 ꢀs, 1H,
37.1, 129.6, 128.8, 128.8, 128.5, 128.5, 128.2, 128.2,
27.6, 127.1, 127.1, 65.1. EI MS ꢀm/z, %): 211 ꢀM , 43),
81 ꢀ71), 135 ꢀ61), 105 ꢀ23), 91 ꢀ100), 77 ꢀ12), 65 ꢀ7), 51
3
1
imidazole-C2±H), 7.04 ꢀd, 1H, Jˆ1.6 Hz, imidazole-C4±
H), 6.93 ꢀd, 1H, Jˆ1.6 Hz, imidazole-C5±H), 6.74 ꢀdd,
1H, Jˆ17.5, 1.5 Hz, vinylic-CH), 5.12 ꢀdd, 1H, Jˆ17.5,
ꢀ5). Anal. calcd for C H NO: C, 79.59; H, 6.20; N, 6.63.
14 13
Found: C, 79.65; H, 6.11; N, 6.71.
10.5 Hz, vinylic-CH ), 4.72 ꢀdd, 1H, Jˆ10.5, 1.7 Hz,
2
1
3
vinylic-CH ). C NMR ꢀ63 MHz, CDCl ): d 135.9, 130.0,
2
3
1
129.3, 115.7, 101.4. EI MS ꢀm/z, %): 94 ꢀM , 100), 67 ꢀ11),
3
.3.9. N,N-Dibenzylbenzamide ꢀ7b). Yield: 180 mg ꢀ60%).
Colorless compound. Mp 78±798C. R ˆ0.83 ꢀhexane/ethyl
40 ꢀ16), 27 ꢀ24). Anal. calcd for C H N : C, 63.81; H, 6.43;
5
N, 29.74. Found: C, 63.90; H, 6.35; N, 29.83.
f
6
2
acetate, 5:2). IR ꢀKBr): 3042, 2928, 2824, 1686, 1632, 1494,
2
245, 1058, 784, 728 cm . H NMR ꢀ250 MHz, CDCl ): d
1 1
1
7
3
.50±7.32 ꢀm, 5H, Ar-H), 7.31±7.21 ꢀm, 10H, Ar-H), 4.53
3.3.14. N-Benzylbenzimidazole ꢀ10a). Yield: 190 mg
ꢀ94%). Colorless compound. Mp 115±1178C ꢀlit. mp
1
3
34
ꢀ
s, 4H, benzyl-CH2). C NMR ꢀ63 MHz, CDCl ): d 166.5,
3
1
1
1
2
7
38.5, 138.4, 138.4, 128.7, 128.6, 128.6, 128.6, 128.6,
28.5, 128.5, 128.4, 128.4, 127.9, 127.9, 127.7, 127.7,
27.7, 127.7, 72.2, 72.2. EI MS ꢀm/z, %): 301 ꢀM , 32),
116±1188C). R ˆ0.70 ꢀhexane/ethyl acetate, 5:2). IR
f
ꢀKBr): 3006, 2942, 2154, 1609, 1466, 1184, 1075, 756,
722, 694 cm . H NMR ꢀ250 MHz, CDCl ): d 7.97 ꢀs,
1
21
1
3
10 ꢀ53), 181 ꢀ18), 135 ꢀ42), 119 ꢀ51), 105 ꢀ31), 91 ꢀ100),
7 ꢀ18), 65 ꢀ10), 51 ꢀ7). Anal. calcd for C H NO: C, 83.69;
1H, imidazole-C2±H), 7.66±7.26 ꢀm, 4H, Ar-H), 7.21±
7.07 ꢀm, 5H, Ar-H), 5.52 ꢀs, 2H, benzyl-CH2). C NMR
1
3
2
1
19
H, 6.35; N, 4.65. Found: C, 83.75; H, 6.27; N, 4.74.
ꢀ63 MHz, CDCl ): d 139.6, 136.8, 133.3, 128.7, 128.7,
3
1
27.8, 127.2, 127.2, 126.5, 124.3, 121.2, 120.8, 109.3,
1
3
Colorless needle. Mp 113±1158C ꢀlit.
.3.10. N-Benzylphthalimide ꢀ8a). Yield: 220 mg ꢀ95%).
mp 109±1108C).
53.0. EI MS ꢀm/z, %): 208 ꢀM , 53), 180 ꢀ72), 153 ꢀ81),
131 ꢀ43), 104 ꢀ25), 91 ꢀ100), 77 ꢀ11), 65 ꢀ13), 51 ꢀ9). Anal.
calcd for C H N : C, 80.74; H, 5.81; N, 13.45. Found: C,
3
1,32
R ˆ0.42 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr): 3058, 2917,
f
14 12
2
2
674, 1648, 1611, 1472, 1346, 1232, 762, 732 cm . H
1
1
1
80.68; H, 5.89; N, 13.38.
NMR ꢀ250 MHz, CDCl ): d 7.82 ꢀdd, 2H, Jˆ8.1, 1.8 Hz,
3
Ar-H), 7.68 ꢀdd, 2H, Jˆ8.1, 1.8 Hz, Ar-H), 7.42±7.25ꢀm,
3.3.15. N-Isopropylbenzimidazole ꢀ10b). Yield: 80 mg
ꢀ48%). Oily compound. R ˆ0.36 ꢀhexane/ethyl acetate,
1
H, Ar-H), 4.84 ꢀs, 2H, benzyl-CH ). C NMR ꢀ63 MHz,
3
5
CDCl ): d 168.0, 168.0, 136.4, 133.9, 133.9, 132.2, 132.2,
2
f
5:4). IR ꢀCHCl ): 3014, 2923, 2156, 1602, 1472, 1175,
3
3
2
1 1
1064, 758, 728, 688 cm . H NMR ꢀ250 MHz, CDCl ): d
1
28.6, 128.6, 128.7, 128.7, 127.8, 123.3, 123.3, 41.7. EI MS
m/z, %): 237 ꢀM , 100), 208 ꢀ61), 180 ꢀ41), 165 ꢀ36), 130
3
1
ꢀ
ꢀ
7.83 ꢀs, 1H, imidazole-C2±H), 7.63±7.09 ꢀm, 4H, Ar-H),
1
3
26), 104 ꢀ14), 91 ꢀ74), 77 ꢀ11), 64 ꢀ9), 51 ꢀ7). Anal. calcd
4.44 ꢀs, 1H, N±H), 1.42 ꢀd, 6H, Jˆ6.7 Hz, CH ). C NMR
3
for C H NO : C, 75.94; H, 4.67; N, 5.90. Found: C, 75.98;
11
ꢀ63 MHz, CDCl ): d 143.8, 140.1, 122.6, 122.2, 122.0,
3
1
5
2
1
120.2, 110.2, 47.7, 22.5, 22.5. EI MS ꢀm/z, %): 160 ꢀM ,
H, 4.75; N, 5.82.
53), 145 ꢀ100), 130 ꢀ31), 117 ꢀ22), 101 ꢀ11), 91 ꢀ52), 77
ꢀ16), 65 ꢀ8), 44 ꢀ9). Anal. calcd for C H N : C, 74.97; H,
7.55; N, 17.48. Found: C, 74.88; H, 7.64; N, 17.4.
3
Colorless needle. Mp 82±848C ꢀlit.
.3.11. N-Isopropylphthalimide ꢀ8b). Yield: 90 mg ꢀ51%).
mp 83±858C).
1
0
12
2
3
2,33
R ˆ0.65 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr): 3064,
f
2
7
914, 1684, 1646, 1617, 1508, 1352, 1223, 1053, 767,
38 cm . H NMR ꢀ250 MHz, CDCl ): d 7.86 ꢀdd, 2H,
3.3.16. N-Benzylindole ꢀ11a). Yield: 190 mg ꢀ92%). Color-
less compound. Mp 41±438C ꢀlit.
2
1
1
10,25a
mp 40±428C).
R ˆ0.89 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr): 3002,
3
Jˆ8.2, 1.9 Hz, Ar-H), 7.74 ꢀdd, 2H, Jˆ8.2, 1.9 Hz, Ar-H),
f
1
3
4
NMR ꢀ63 MHz, CDCL ): d 168.4, 168.4, 133.7, 133.7,
.52 ꢀm, 1H, N±CH), 1.49 ꢀd, 6H, Jˆ6.9 Hz, CH ).
C
2982, 2142, 1465, 1342, 1203, 1095, 1024, 765, 735,
642 cm . H NMR ꢀ250 MHz, CDCl ): d 7.63±7.37 ꢀm,
3
2
1 1
3
3
1
32.2, 132.2, 123.0, 123.0, 43.0, 20.1, 20.1. EI MS ꢀm/z,
4H, Ar-H), 7.31±7.16ꢀm, 5H, Ar-H), 6.96 ꢀd, 1H, Jˆ2.8 Hz,
1
%
): 189 ꢀM , 21), 174 ꢀ100), 160 ꢀ43), 147 ꢀ38), 130
27), 102 ꢀ31), 77 ꢀ13), 66 ꢀ9), 51 ꢀ4). Anal. calcd for
C H NO : C, 69.83; H, 5.86; N, 7.40. Found: C, 69.71;
indole-C2±H), 6.65 ꢀd, 1H, Jˆ2.8 Hz, indole-C3±H), 5.31
1
3
ꢀ
ꢀs, 2H, benzyl-CH ). C NMR ꢀ63 MHz, CDCl ): d 139.6,
2 3
136.8, 133.2, 128.7, 128.7, 127.8, 127.3, 127.3, 126.5,
124.3, 121.3, 120.8, 109.4, 101.8, 50.0. EI MS ꢀm/z, %):
1
1
11
2
H, 5.79; N, 7.36.
1
07 ꢀM , 100), 169 ꢀ41), 130 ꢀ21), 116 ꢀ13), 91 ꢀ51), 77
2
3
less needle. Mp 71±738C ꢀlit.
.3.12. N-Benzylimidazole ꢀ9a). Yield: 150g ꢀ94%). Color-
mp 728C). R ˆ0.38
ꢀ17), 64 ꢀ9). Anal. calcd for C H N: C, 86.92; H, 6.32; N,
15 13
6.76. Found: C, 86.87; H, 6.41; N, 6.69.
2
4f,34
f
ꢀ
hexane/ethyl acetate, 5:4). IR ꢀKBr): 3012, 2924, 2144,
2
606, 1434, 1185, 1068, 786, 758 cm . H NMR
1
1
24e,g
1
3.3.17. N-Benzylpyrrole ꢀ12a).
Yield: 140 mg ꢀ91%).
ꢀ
6
250 MHz, CDCl ): d 7.42 ꢀs, 1H, imidazole-C2±H), 7.22±
3
.99 ꢀm, 5H, Ar-H), 7.11 ꢀd, 1H, Jˆ1.3 Hz, imidazole-C4±
Oily compound. R ˆ0.91 ꢀhexane/ethyl acetate, 5:2). IR
f
ꢀCHCl ): 3018, 2918, 2832, 2126, 1656, 1432, 1208,
3
2
1065, 775, 745 cm . H NMR ꢀ250 MHz, CDCl ): d
1
1
H), 6.75 ꢀd, 1H, Jˆ1.3 Hz, imidazole-C5±H), 4.95 ꢀs, 2H,
3
1
3
benzyl-CH ). C NMR ꢀ63 MHz, CDCl ): d 137.4, 136.2,
7.23±6.99 ꢀm, 5H, Ar-H), 6.59 ꢀd, 2H, Jˆ2.7 Hz, pyrrole-
13
2
3
1
ꢀ
29.6, 128.9, 128.9, 128.2, 127.3, 127.3, 119.4, 50.8. EI MS
m/z, %): 158 ꢀM , 41), 106 ꢀ65), 91 ꢀ100), 76 ꢀ17), 65 ꢀ23),
C2/C5-H/H), 6.11 ꢀd, 2H, Jˆ2.7 Hz, pyrrole-C3/C4±H/H),
1
4.95 ꢀs, 2H, benzyl-CH ). C NMR ꢀ63 MHz, CDCl ): d
138.3, 129.9, 128.8, 128.8, 127.1, 127.1, 121.3, 121.3,
108.6, 108.6, 53.4. EI MS ꢀm/z, %): 157 ꢀM , 46), 91
2
3
5
N, 17.71. Found: C, 76.01; H, 6.29; N, 17.81.
1 ꢀ13), 41 ꢀ8). Anal. calcd for C H N : C, 75.92; H, 6.37;
1
0
10
2
1
ꢀ100), 77 ꢀ18), 65 ꢀ11), 51 ꢀ9). Anal. calcd for C H N:
11 11
3
.3.13. N-Vinylimidazole ꢀ9b). Yield: 60 mg ꢀ66%). Oily
C, 84.08; H, 7.05; N, 8.91. Found: C, 83.95; H, 7.15; N,
8.80.
compound. Rfˆ0.28 ꢀhexane/ethyl acetate, 5:4). IR

9956
S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
3
.3.18. N-Benzylpyrazole ꢀ13a). Yield: 150 mg ꢀ96%).
5
1
17.7. EI MS ꢀm/z, %): 175 ꢀM , 100), 146 ꢀ11), 131 ꢀ16),
3
Oily compound. R ˆ0.55 ꢀhexane/ethyl acetate, 5:2). IR
118 ꢀ22), 104 ꢀ9), 91 ꢀ56), 84 ꢀ8), 78 ꢀ25), 65 ꢀ10), 51 ꢀ13).
Anal. calcd for C H NO: C, 75.40; H, 7.48; N, 7.99.
Found: C, 75.46; H, 7.36; N, 7.92.
f
ꢀ
CHCl ): 3066, 2915, 2175, 1452, 1341, 1214, 1096, 761,
3
11 13
2
45 cm . H NMR ꢀ250 MHz, CDCl ): d 7.41 ꢀd, 1H,
1
1
6
3
Jˆ4.8 Hz, pyrazole-C3±H), 7.38 ꢀd, 1H, Jˆ8.5 Hz, pyra-
zole-C5±H), 7.15±6.98 ꢀm, 5H, Ar-H), 6.11 ꢀdd, 1H, Jˆ8.5,
3.3.23. N-Benzyl-1-2-4-triazole ꢀ18a). Yield: 70 mg
1
3
4
NMR ꢀ63 MHz, CDCl ): d 139.6, 136.7, 129.6, 128.8,
.8 Hz, pyrazole-C4±H), 5.07 ꢀs, 2H, benzyl-CH ).
C
ꢀ44%). Yellow prisms. Mp 65±678C. R ˆ0.60 ꢀhexane/
f
2
ethyl acetate, 5:2). IR ꢀKBr): 3016, 2936, 2132, 1606,
3
2
1
1
1
1
28.8, 128.0, 127.6, 127.6, 106.1, 55.7. EI MS ꢀm/z, %):
58 ꢀM , 41), 130 ꢀ19), 91 ꢀ42), 76 ꢀ24), 68 ꢀ100), 51
1452, 1072, 1072, 752, 732, 692 cm . H NMR
ꢀ250 MHz, CDCl ): d 8.45 ꢀs, 1H, triazole-C3±H), 7.90
ꢀs, 1H, triazole-C5±H), 7.26±7.17 ꢀm, 5H, Ar-H), 5.29 ꢀs,
1
3
ꢀ21), 42 ꢀ15). Anal. calcd for C H N : C, 75.92; H, 6.37;
10 10 2
N, 17.7. Found: C, 75.86; H, 6.42; N, 17.67.
1
3
2H, benzyl-CH
144.9, 136.7, 129.9, 129.9, 129.4, 129.1, 129.1, 54.2. EI
). C NMR ꢀ63 MHz, CDCl ): d 152.2,
2 3
1
3
.3.19. N-Benzylindazole ꢀ14a). Yield: 180 mg ꢀ90%).
MS ꢀm/z, %): 159 ꢀM , 100), 132 ꢀ64), 104 ꢀ11), 91 ꢀ21),
77 ꢀ9), 65 ꢀ13), 51 ꢀ7). Anal. calcd for C : C, 67.91; H,
5.70; N, 26.40. Found: C, 67.99; H, 5.63; N, 26.45.
Colorless compound. Mp 91±938C. R ˆ0.68 ꢀhexane/ethyl
H N
9 9 3
f
acetate, 5:2). IR ꢀKBr): 3010, 2938, 2168, 1614, 1452, 1184,
2
074, 754, 724, 696 cm . H NMR ꢀ250 MHz, CDCl ): d
1 1
1
7
7
3
.98 ꢀs, 1H, indazole-C3±H), 7.67±7.26 ꢀm, 4H, Ar-H),
.23±7.11 ꢀm, 5H, Ar-H), 5.53 ꢀs, 2H, benzyl-CH2).
3.3.24. N-Ethylpiperidine ꢀ19a). Yield: 50 mg ꢀ42%). Oily
1
3
C
compound.
ꢀCHCl ): 3042, 2942, 2814, 1262, 1038, 768, 728 cm .
H NMR ꢀ250 MHz, CDCl
): d 3.48 ꢀq, 2H, Jˆ6.9 Hz,
CH CH ), 2.51 ꢀm 4H, piperidine-C2/C6±H /H ), 1.83 ꢀm,
4H, piperidine-C3/C5±H /H ), 1.49 ꢀm, 2H, piperidine-C4±
), 1.31 ꢀt, 3H, Jˆ6.9 Hz, CH
CDCl ): d 56.1, 56.1, 42.2, 21.4, 21.4, 17.4, 11.8. EI MS
m/z, %): 113 ꢀM , 100), 98 ꢀ56), 84 ꢀ42), 70 ꢀ11), 56 ꢀ21),
42 ꢀ13). Anal. calcd for C 15N: C, 74.27; H, 13.36; N,
R
ˆ0.79 ꢀhexane/ethyl acetate, 5:2). IR
f
2
1
NMR ꢀ63 MHz, CDCl ): d 139.6, 136.8, 133.3, 128.8,
3
3
1
1
1
28.8, 127.8, 127.3, 127.3, 126.6, 124.4, 121.3, 120.8,
09.4, 53.0. EI MS ꢀm/z, %): 208 ꢀM , 64), 180 ꢀ12), 153
3
1
2
3
2
2
ꢀ31), 131 ꢀ16), 104 ꢀ9), 91 ꢀ100), 77 ꢀ6), 65 ꢀ13), 51 ꢀ5).
Anal. calcd for C H N : C, 80.74; H, 5.81; N, 13.45.
Found: C, 80.65; H, 5.87; N, 13.36.
2
2
1
3
H
2
CH ). C NMR ꢀ63 MHz,
2 3
1
4
12
2
3
1
ꢀ
3
.3.20. N-Benzylindoline ꢀ15a). Yield: 210 mg ꢀ98%).
6
3
H
7
Yellow oily. R ˆ0.93 ꢀhexane/ethyl acetate, 5:2). IR
12.37. Found: C, 74.36; H, 13.28; N, 12.42.
f
ꢀ
CHCl ): 3005, 2962, 2921, 2824, 1615, 1486, 1456,
3
2
358, 904, 741 cm . H NMR ꢀ250 MHz, CDCl ): d
1
1
1
7
3
.47±7.35 ꢀm, 5H, Ar-H), 7.19±6.64 ꢀm, 4H, Ar-H) 4.35
Acknowledgements
ꢀ
s, 2H, benzyl-CH ), 3.41 ꢀt, 2H, Jˆ8.2 Hz, indoline-C2±
2
1
3
H ), 3.06 ꢀt, 2H, Jˆ8.2 Hz, indoline-C3±H ). C NMR
We express our gratitude to the Deutsche Akademische
Austauschdienst ꢀDAAD, Bonn, Germany) for a sandwich-
type scholarship granted to Safdar Hayat.
2
2
ꢀ
63 MHz, CDCl ): d 152.6, 138.5, 130.2, 128.1, 128.1,
3
1
2
27.7, 127.7, 127.4, 126.9, 124.6, 118.0, 107.3, 53.9, 53.7,
8.7. EI MS ꢀm/z, %): 209 ꢀM , 100), 132 ꢀ21), 118 ꢀ16), 91
1
ꢀ
C H N: C, 86.08; H, 7.22; N, 6.69. Found: C, 86.16; H,
48), 77 ꢀ25), 65 ꢀ10), 51 ꢀ15), 42 ꢀ9). Anal. calcd for
1
5
15
References
7
.17; N, 6.76.
1
. ꢀa) Clark, J. H.; Holland, H. L.; Miller, J. M. Tetrahedron Lett.
1976, ꢀ8, 3361±3364. ꢀb) Clark, J. H.; Miller, J. M.
Tetrahedron Lett. 1977, 7, 599±602. ꢀc) Clark, J. H.; Miller,
J. M. J. Am. Chem. Soc. 1977, 99, 498±504. ꢀd) Clark, J. H.;
Miller, J. M. J. Chem. Soc., Perkin Trans. 1 1977, 2063±2069.
3
Colorless needle. Mp 117±1198C ꢀlit.
.3.21. N-Benzylcarbazole ꢀ16a). Yield: 240 mg ꢀ93%).
mp 118±
1
0,24a
1
3
7
218C). R ˆ0.77 ꢀhexane/ethyl acetate, 5:2). IR ꢀKBr):
f
075, 2909, 1645, 1611, 1502, 1473, 1354, 1225, 1165,
64, 734 cm . H NMR ꢀ250 MHz, CDCl ): d 8.06±8.02
2
1 1
3
2. ꢀa) Clark, J. H.; Miller, J. M. J. Chem. Soc., Chem. Commun.
1976, 229±230. ꢀb) Clark, J. H.; Miller, J. M. J. Chem. Soc.,
Chem. Commun. 1977, 64±65. ꢀc) Miller, J. M.; So, K.-H.;
Clark, J. H. J. Chem. Soc., Chem. Commun. 1978, 466±467.
ꢀd) Clark, J. H. J. Chem. Soc., Chem. Commun. 1978, 778±
789.
ꢀm, 2H, Ar-H), 7.36±7.18 ꢀm, 6H, Ar-H), 7.17±7.00 ꢀm, 5H,
Ar-H), 5.37 ꢀs, 2H, benzyl-CH2). C NMR ꢀ63 MHz,
CDCl ): d 140.8, 140.8, 137.3, 128.8, 128.8, 127.5, 126.5,
3
1
3
1
1
1
26.5, 125.9, 125.9, 123.2, 123.2, 120.5, 120.5, 119.3,
1
19.3, 109.0, 109.0, 46.6. EI MS ꢀm/z, %): 257 ꢀM , 83),
80 ꢀ11), 166 ꢀ31), 140 ꢀ17), 129 ꢀ9), 91 ꢀ100), 77 ꢀ8), 65
3. Lee, J. C.; Choi, Y. Synth. Commun. 1998, 28, 2021±2026.
4. ꢀa) Voss, W.; Blanke, E. Justus Liebigs Ann. Chem. 1931, 485,
280. ꢀb) Ishikawa, N.; Kitazume, T.; Nakabayashi, M. Chem.
Lett. 1980, 1089±1090. ꢀc) Giuamanini, A. G.; Chiavari, G.;
Musiani, M. M.; Rossi, P. Synthesis 1980, 9, 743±746.
5. ꢀa) Hutchins, R. O.; Markowitz, M. J. Org. Chem. 1981, 46,
3571±3574. ꢀb) Onaka, M.; Umezono, A.; Kawai, M.; Izumi,
Y. J. Chem. Soc., Chem. Commun. 1985, 17, 1202±1203.
ꢀc) Kim, S.; Oh, C. H.; Ko, J. S.; Ahn, K. H.; Kim, Y. J. J.
Org. Chem. 1985, 50, 1927±1932.
ꢀ
11), 51 ꢀ7). Anal. calcd for C H N: C, 88.68; H, 5.88; N,
19 15
5
.44. Found: C, 88.58; H, 5.96; N, 5.39.
3
.3.22. N-Benzyl-2-pyrrolidinone ꢀ17a). Yield: 160 mg
ꢀ
5
90%). Oily compound. R ˆ0.52 ꢀhexane/ethyl acetate,
2
452, 1354, 1042, 902, 735 cm . H NMR ꢀ250 MHz,
f
:4). IR ꢀCHCl ): 3004, 2964, 2831, 1690, 1618, 1470,
3
1
1
1
CDCl ): d 7.27±7.13 ꢀm, 5H, Ar-H), 4.35 ꢀs, 2H, benzyl-
3
CH ), 3.14 ꢀt, 2H, Jˆ3.4 Hz, pyrrolidinone-C5±H ), 2.32 ꢀt,
2
2
2
lidinone-C4±H ). C NMR ꢀ63 MHz, CDCl ): d 174.9,
H, Jˆ3.4 Hz, pyrrolidinone-C3±H ), 1.84 ꢀm, 2H, pyrro-
6. ꢀa) Gribble, G. W.; Nutaitis, C. F. Synthesis 1987, 8, 709±711.
ꢀb) Lissel, M.; Rohani-Dezfuli, A. Z.; Vogt, G. J. Chem. Res.,
Miniprint 1989, 10, 2434±2452. ꢀc) Selva, M.; Bomben, A.;
2
1
3
2
3
1
36.6, 128.6, 128.6, 128.1, 128.1, 127.6, 72.1, 46.6, 30.9,

S. Hayat et al. / Tetrahedron 57 32001) 9951±9957
9957
Tundo, P. J. Chem. Soc., Perkin Trans. 1 1997, 7, 1041±1046.
d) Valot, F.; Fache, F.; Jacquot, R.; Spagnol, M.; Lemaire, M.
Tetrahedron Lett. 1999, 19, 3689±3692.
23. Candy, C. F.; Jones, R. A. J. Org. Chem. 1971, ꢀ6, 3993±
3994.
ꢀ
24. ꢀa) Nishi, H.; Kohno, H.; Kano, T. Bull. Chem. Soc. Jpn 1981,
54, 1897±1898. ꢀb) Davidson, R. S.; Patel, A. M.; Safdar, A.;
Thornthwaite, D. Tetrahedron Lett. 1983, 24, 5907±5910.
ꢀc) Trotta, F.; Tundo, P.; Moraglio, G. J. Org. Chem. 1987,
52, 1300±1304. ꢀd) Diez-Barra, E.; de La Hoz, A.; Sanchez-
Migallon, A.; Tejeda, J. Synth. Commun. 1990, 20, 2849±
7
8
. Matsuhashi, M.; Arata, K. Bull. Chem. Soc. Jpn 1991, 64,
605±2606.
2
. ꢀa) Takamiya, N.; Koinuma, Y.; Ando, K.; Murai, S. Nippon
Kagaku Kaishi 1979, 1453. ꢀb) Takamiya, N.; Yamabe, H.;
Ando, K.; Murai, S. Nippon Kagaku Kaishi 1980, 1316.
. ꢀa) Watanabe, Y.; Tsuji, Y.; Ohsugi, Y. Tetrahedron Lett.
2853. ꢀe) Hamaide, T. Synth. Commun. 1990, 20, 2913±
2920. ꢀf) Diez-Barra, E.; de La Hoz, A.; Sanchez-Migallon,
9
1
981, 22, 2667±2670. ꢀb) Watanabe, Y.; Tsuji, Y.; Ige, H.;
Ohsugi, Y.; Ohta, T. J. Org. Chem. 1984, 49, 3359±3363.
c) Huh, K.-T.; Tsuji, Y.; Kobayashi, M.; Okuda, F.;
Watanabe, Y. Chem. Lett. 1988, 449±452.
0. Bergman, J.; Norrby, P.-O.; Sand, P. Tetrahedron 1990, 46,
113±6124.
1. Onaka, M.; Ishikawa, K.; Izumi, Y. Chem. Lett. 1982, 1783±
786.
2. Barton, D. H. R.; Ozbalik, N.; Ramesh, M. Tetrahedron Lett.
988, 29, 857±860.
A.; Tejeda, J. Synth. Commun. 1993, 2ꢀ, 1783±1786. ꢀg) Diez-
Barra, E.; de La Hoz, A.; Loupy, A.; Sanchez-Migallon, A.
J. Heterocycl. Chem. 1994, ꢀ1, 1715±1717.
ꢀ
2
5. ꢀa) Santaniello, E.; Farachi, C.; Ponti, F. Synthesis 1979, 617±
1
1
1
1
618. ꢀb) Guida, W. C.; Mathre, D. J. J. Org. Chem. 1980, 45,
3172±3176.
6
26. Sukata, K. Bull. Chem. Soc. Jpn 1983, 56, 280±284.
27. ꢀa) Bogdal, D.; Pielichowski, J.; Jaskot, K. Synth. Commun.
1
1
997, 27, 1553±1560. ꢀb) Bogdal, D.; Pielichowski, J.; Jaskot,
1
K. Heterocycles 1997, 45, 715±722. ꢀc) Abenhaim, D.; Diez-
Barra, E.; de La Hoz, A.; Loupy, A.; Sanchez-Migallon, A.
Heterocycles 1994, ꢀ8, 793. ꢀd) Perez, E.; Sotelo, E.; Loupy,
A.; Mocelo, R.; Suarez, M.; Perez, R.; Autie, M. Heterocycles
3. ꢀa) Freifelder, M. Practical Catalytic Hydrogenation; Wiley-
Interscience: New York, 1971; pp 333±389. ꢀb) Freifelder, M.
Catalytic Hydrogenation in Organic Synthesis Procedures
and Commentary; Wiley: New York, 1978; pp 90±95.
1
996, 4ꢀ, 539.
8. Jaisinghani, H. G.; Khadilkar, B. M. Synth. Commun. 1999,
9, 3693±3698.
9. ꢀa) Pfeffer, P. E.; Silbert, L. S. J. Org. Chem. 1976, 41, 1373±
ꢀc) James, B. R. Homogeneous Hydrogenation; Wiley: New
York, 1973; pp 135±137.
2
2
2
1
1
1
1
1
1
4. ꢀa) Walker, E. R. H. Chem. Soc. Rev. 1976, 5, 23. ꢀb) Junko,
Y.; Takashi, A.; Terukiyo, H. Chem. Lett. 1981, 1143±1146.
5. See for example, Mattingly, P. G.; Miller, M. J. J. Org. Chem.
1
379. ꢀb) Lerchen, H. G.; Kunz, H. Tetrahedron Lett. 1985,
6, 5257±5260. ꢀc) Kunz, H.; Lerchen, H. G. Tetrahedron
2
1
981, 46, 1557±1564.
Lett. 1987, 28, 1873±1876. ꢀd) Luthman, K.; Orbe, M.;
Waglund, T.; Claesson, A. J.Org. Chem. 1987, 52, 3777±
6. March, J. Advanced Organic Chemistry, Vol. 4; Wiley: New
York, 1992; pp 653.
3
784. ꢀe) Sato, T.; Otera, J.; Nozaki, H. J.Org. Chem. 1992,
7, 2166±2169.
7. Suga, K.; Watanabe, S.; Fujita, T.; Pan, T. P. Bull. Chem. Soc.
Jpn 1969, 42, 3606±3608.
5
3
3
3
0. Katritzky, A. R.; Yao, G.; Lan, X.; Zhao, X. J. Org. Chem.
993, 58, 2086±2093.
1. Lee, D. A.; Hanaa, I. A.; John, C. V. J. Am. Chem. Soc. 1989,
11, 3973±3976.
8. Mohri, K.; Suzuki, K.; Usui, M.; Isobe, K.; Tsuda, Y. Chem.
Pharm. Bull. 1995, 4ꢀ, 159±161.
9. ꢀa) Kikugawa, Y.; Miyaka, Y. Synthesis 1981, 6, 461±462.
1
1
ꢀ
b) Heany, H.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1
973, 5, 499±500.
0. ꢀa) Hobbs, C. F.; Mcmillin, C. K.; Papadopoulos, E. P.;
2. Jeong, I.-Y.; Lee, W. S.; Goto, S.; Sano, S.; Shiro, M.; Nagao,
Y. Tetrahedron 1998, 54, 14437±14454.
1
2
3
3. Kehler, J.; Breuer, E. Synthesis 1998, 10, 1419±1420.
4. Lionel, R. M.; Philip, J. F. D.; Gokhan, Y. Tetrahedron 1996,
Vanderwerf, C. A. J. Am. Chem. Soc. 1962, 84, 43±51.
b) Papadopoulos, E. P.; Tabello, K. I. Y. J. Org. Chem.
968, ꢀꢀ, 1299±1300.
3
ꢀ
52, 9877±9890.
5. Begtrup, M. Acta Chem. Scand. 1973, 27, 1301±3110.
1
3
3
2
1. Potts, K. T.; Saxton, J. E. Org. Synth. 1960, 40, 68±70.
2. Rubotton, G. M.; Chabala, J. C. Org. Synth. 1974, 54, 60±62.
6. Miroslaw, J. T.; John, W.; Nick, H. W. Aust. J. Chem. 1995,
4
2
8, 291±321.