One-pot conversion of β-aminocrotononitrile to secondary enaminonitriles including chiral ones - Application to synthesis

Article abstract of DOI:10.1139/v05-143

A highly efficient one-pot conversion of β-aminocrotononitrile to secondary enaminonitriles including chiral ones is described. In contrast to β-aminocrotononitrile, some of these N-substituted β-enaminonitriles on reacting with acid chlorides show a unique preference for C-terminal selection allowing preparation of pyrazoles without separation of regioisomers. In addition, use of secondary enaminonitriles also provided access to pyrazoles that are not obtainable with primary enaminonitriles owing to an exclusive preference for N-terminal selection.

Full text of DOI:10.1139/v05-143

1164
One-pot conversion of ␤-aminocrotononitrile to
secondary enaminonitriles including chiral ones —
Application to synthesis
A. Chatterjee, M. Mishra, S.K. Dutta Chowdhury, and Kumar K. Mahalanabis
Abstract: A highly efficient one-pot conversion of β-aminocrotononitrile to secondary enaminonitriles including chiral
ones is described. In contrast to β-aminocrotononitrile, some of these N-substituted β-enaminonitriles on reacting with
acid chlorides show a unique preference for C-terminal selection allowing preparation of pyrazoles without separation
of regioisomers. In addition, use of secondary enaminonitriles also provided access to pyrazoles that are not obtainable
with primary enaminonitriles owing to an exclusive preference for N-terminal selection.
Key words: β-aminocrotononitrile, N-substituted enaminonitriles, regioselective, pyrazoles.
Résumé : On décrit une méthode unipot très efficace de conversion du $-aminocrotononitrile en énaminonitriles secon-
daires, y compris ceux de nature chirale. Contrairement à ce qui est observé avec le $-aminocrotononitrile, certains de
ces $-énaminonitriles N-substitués réagissent avec les chlorures d’acides avec une préférence unique pour la position C-
terminale, ce qui permet de préparer des pyrazoles sans avoir à séparer les régioisomères. De plus, l’utilisation
d’énaminonitriles secondaires permet aussi d’accéder à des pyrazoles qui ne peuvent pas être obtenus à partir de
l’énaminonitrile primaire en raison de la préférence exclusive pour la sélection N-terminale.
Mots clés : $-aminocrotononitrile, énaminonitriles N-substitués, régiosélective, pyrazoles.
[Traduit par la Rédaction] Chatterjee et al. 1170
Introduction
realize this objective we decided to explore secondary
enaminonitriles instead of 1 in our acylation study and to
observe if there was any change in preference for terminal
selection with regard to 1. This contemplated study required
preparation of a large number of secondary enaminonitriles
in reasonably good yields under mild conditions. Several
methods of preparation of N-substituted enaminonitriles are
reported in the literature (12–17), but most of these em-
ployed indirect methods and thus are not suitable for a pre-
paratory scale. Dedina et al. (16) reported three different
procedures for the preparation of N-substituted-3-aminocro-
tononitrile: procedure A uses a solution of enaminonitrile
and an amine in ethanol in an autoclave at 130–136 °C for
5–8 h. In procedure B, a solution of HCl (6 mol/L) in etha-
nol was added to a dioxane solution of enaminonitrile and
amine and the mixture was heated for 5 to 6 h in a pressure
tube at 120–140 °C. Procedure C involves heating a mixture
of enaminonitrile and amine without any solvent. In our
study we observed that the use of HCl or the absence of
ethyl alcohol resulted in extensive polymerization of the
enaminonitrile itself and the yield of the secondary enamino-
nitrile was poor. For example, we obtained N-phenyl-β-
aminocrotononitrile (2g) in an 87% yield when the reaction
was carried out in the presence of an alcohol, whereas in the
case of procedure C as described by Dedina et al. (16) the
yield of 2g was reported to be only 37%.
The chemistry of β-aminocrotononitrile is well-documented
(1) and continues to remain an active area for further study.
For some time now we have been engaged in systematic
studies on the acylation reactions of β-aminocrotononitrile
(1) with acid chlorides in the presence of an added organic
base to evaluate preferences for regioselection (2–5) and to
explore the utility of the derived products for synthesis of
novel heterocyclic compounds (6–9). β-Acylenaminonitriles
behave as masked 1,3-diketones and are considered to be
useful intermediates (10) particularly in heterocyclic chemis-
try (11). Results reported from this laboratory on acylation
reactions of primary enaminonitriles with acid chlorides al-
though indicating a high degree of preference for terminal
selection depending on the choice of acid chlorides used,
nevertheless indicate that there is room to develop new
routes to ensure exclusive acylation at the C-terminal partic-
ularly in those cases where either N-acylation occurred or a
mixture of C- and N-acylated products were obtained. To
Received 13 December 2004. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 24 September
2005.
A. Chatterjee, M. Mishra, and K.K. Mahalanabis.1
Department of Chemistry, Jadavpur University, Kolkata
700 032, India.
S.K. Dutta Chowdhury. Department of Chemistry, Jadavpur
University, Kolkata 700 032, India, and Jogesh Chandra
Chowdhury College, Kolkata 700 033, India.
Lack of a general approach, consistency in yields, and in-
adequacies of N-substituent variants leave significant room
for improvement in the methodology for preparation of sec-
ondary enaminonitriles notwithstanding the extensive work
done by Dedina et al. (16). Herein, we report a very simple,
1Corresponding author (e-mail: kkmahalanabis@yahoo.co.in).
Can. J. Chem. 83: 1164–1170 (2005)
doi: 10.1139/V05-143
© 2005 NRC Canada

Chatterjee et al.
1165
Table 1. Data for prepared compounds 2a–2p.
Compound
R
Yield (%)a
mp (°C) or bp (°C)
[α]25 (°) (c 0.5 in CHCl3)
D
54 to 55 (lit. value (16) mp 54 to 55)
45 (lit. value (16) mp 45 to 46)
70 to 71
2a
2b
Me
CH2Me
65
70
—
—
2c
2d
2e
2f
CH2CH2OH
C6H11
76
97
72
84
—
—
—
—
88 to 89 (lit. value (16) mp 88 to 89)
44 to 45
CH2CO2Et
CH2Ph
81 to 82 (lit. value (16) mp 78 to 79)
2g
2h
Ph
87
80
116 (lit. value (16) mp 116 to 117)
126 to 127
—
—
p-MeO·C6H4
2i
2j
o-Me·C6H4
p-Me·C6H4
70
81
65 to 66
90 to 91
—
—
2k
2l
CH(Me)Ph
CH(Me)CO2Me
95
74
65 to 66
150–153 (0.05 mm)
+100
–52
2m
2n
2o
CH(CHMe2)CO2Me
82
71
77
70
160–167 (0.05 mm)
170–175 (0.05 mm)
220–225 (0.01 mm)
195–200 (0.01 mm)
–96.83
–95.6
CH(CH2CHMe2)CO2Me
CH(CH2Ph)CO2Me
+107.42
+119.11
2p
CHCH2(p-HO·C6H4) CO2Me
aYields of isolated products.
Scheme 1.
verted to novel 5-substituted 1,2-azoles (8, 9). Although a
high degree of success was achieved in terminal selection,
there were examples where either a mixture of regioisomers
or only N-acylated products were obtained. Since β-enamin-
ones have proven to be valuable intermediates in the synthe-
sis of a wide variety of heterocyclic compounds (20), we
have initiated this study on the acylation reaction of second-
ary enaminonitriles to observe if there was any change in
their preference for terminal selection when compared to
primary enaminonitriles. Results obtained thus far indicate
that N-substituted β-aminocrotononitriles show a strong pref-
erence for C-terminal selection when compared with the re-
sults obtained earlier for 1 (Scheme 2). Thus, N-benzyl-β-
aminocrotononitrile (2f) on reaction with acid chlorides of
benzoic acid, o-nitrobenzoic acid, m-nitrobenzoic acid, and
thiophene-2-carboxylic acid afforded only C-acylated prod-
ucts in contrast to our earlier results with 1 whereby a mix-
ture of regioisomers 3 and 4 (1:1) was obtained. The presence
of compounds 3 and 4 in the reaction mixture was confirmed
by 1H NMR spectral analysis, and the pure regioisomers
were obtained by column chromatography. A dramatic re-
versal of preference for site selection occurred when
acylation of 2f was carried out with isobutyryl chloride re-
sulting in exclusive C-terminal selection. In an earlier exper-
iment, treatment of 1 with isobutyryl chloride afforded only
the N-acylated product, thereby precluding its use for the
preparation of pyrazole (Scheme 2, Table 2). Such a strong
preference by 2f for C-terminal selection allowed us to syn-
thesize pyrazoles that previously needed either separation of
regioisomers or where the total lack of preference for C-
terminal selection excluded their formation (Scheme 3, Ta-
ble 3). Presently, we are working on the synthetic applica-
tion of other secondary enaminonitriles including chiral ones.
Thus, easy access to secondary enaminonitriles provides a
direct route for the synthesis of heterocycles that otherwise
are not directly obtainable from acylation reactions of pri-
mary enaminonitriles. In addition, the availability of opti-
cally active secondary enaminonitriles is likely to provide
H
H
NC
NC
Me
RNH , dry EtOH
2
Reflux
Me
NH
NHR
2
2
1
direct, and highly efficient general method for the one-pot
preparation of secondary enaminonitriles 2a–2j including
the optically active ones 2k–2p by reacting 1 with amines in
refluxing dry ethyl alcohol (Scheme 1, Table 1). For the
preparation of N-methyl-β-aminocrotononitrile (2a) and N-
ethyl-β-aminocrotononitrile (2b), methyl ammonium chlo-
ride and ethyl ammonium chloride, respectively, were used
in the presence of triethyl amine.
In the case of the optically active enaminonitriles 2k–2p,
the amino acids were first converted to their corresponding
methyl ester hydrochlorides by treatment with thionyl chlo-
ride in refluxing dry methyl alcohol (18, 19). These ester hy-
drochlorides were then reacted with 1 in the presence of
triethyl amine in refluxing ethyl alcohol. The amino acids
used were (S)-(+)-alanine, (S)-(+)-leucine, (S)-(+)-valine,
(R)-(+)-α-methylbenzyl amine, (S)-(–)-phenylalanine, and
(S)-(–)-tyrosine. The homogeneity of the liquid products was
checked by HPLC using a C-18 Bonda-pak column and a
methanol–water (1:1) mixture as the mobile phase. The
structures of these enaminonitriles are supported by consis-
tent elemental and spectral analyses. Careful analysis of the
1H NMR spectra of the isolated products is suggestive of the
E conformation for the enaminonitriles (16). When com-
pared with documented literature methods, the present pro-
cedure scores favorably in terms of simplicity, yields, choice
of N-substituent variants, and purity of the products.
In our earlier investigations (5) on acylation of 1 we dem-
onstrated that by choosing a suitable acid chloride it is pos-
sible to control the site of acylation to a large degree. β-
Acylcyanoenaminonitriles thus obtained were easily con-
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1166
Can. J. Chem. Vol. 83, 2005
Scheme 2.
R1
H
NC
Me
NC
Me
H
O
H
NC
Me
O
R1COCl, dry Benzene
Py, Reflux
N
H
R1
N
NH2
H
1
4
3
R1 = Ph, o-NO2-C6H4, m-NO2-C6H4, 2-thienyl, the product is a mixture (1:1) of 3 and 4
R1 = isobutyryl, the product is only 4
R1
H
NC
Me
NC
Me
O
H
R1COCl, dry Benzene
Py, Reflux
N
NH
CH2Ph
CH2Ph
2f
3a-3e
R1 = Ph, o-NO2-C6H4, m-NO2-C6H4, 2-thienyl, isobutyryl
Table 2. Data for the acylation reaction of N-benzyl-β-
aminocrotononitrile (2f) and prepared compounds 3a–3e.
Scheme 3.
R1
Me
CN
Compound
R
R1
mp (°C)
84 to 85
Yield (%)a
71
NC
O
H
PhNHNH2 ·HCl
NaOAc,
3a
3b
3c
3d
3e
CH2Ph Ph
N
CH2Ph o-NO2-C6H4
137 to 138 67
R1
Me
N
N
CH2Ph m-NO2-C6H4 123 to 124 70
Ph
CH2Ph
CH2Ph 2-Thienyl
CH2Ph Isobutyryl
80 to 81
88 to 89
76
80
5a-5e
3a-3e
aYields of isolated products.
Table 3. Data for prepared compounds 5a–5e.
opportunities for their utilization as chiral auxiliaries to-
wards the synthesis of chiral heterocycles.
Compound
R1
mp (°C)
Yield (%)a
5a
5b
Ph
191 to 192
155 to 156
78
67
o-NO2-C6H4
5c
m-NO2-C6H4
162 to 163
90
5d
5e
2-Thienyl
Isobutyryl
204–206
73 to 74
67
70
Experimental
Melting points were determined in open capillaries. NMR
spectra were recorded using a Brucker AC-300 and (or)
Brucker Avance 400 MHz spectrometer. Elemental analyses
were performed using a PerkinElmer 240C elemental ana-
lyzer, mass spectra were obtained with an Hitachi RMU 6L
and JMS-Ax505H mass spectrometer, and GC–MS spectra
were obtained using an Agilnet 6890N. Optical rotations
were measured on a Jasco Dip 360 digital polarimeter.
HPLC was carried out using a Water Corporation UV detec-
tor and version 2.1 Mellenium software. UV and IR spectra
were obtained using Hitachi U-2000 and Hitachi 270–30
spectrometers, respectively.
aYields of isolated products.
β-Aminocrotononitrile and acid chlorides were prepared
according to literature procedures in refs. 21 and 22, respec-
tively.
General procedure
Preparation of N-substituted ␤-aminocrotononitriles
(a) A mixture of 1 (10 mmol), primary amine (10 mmol),
and dry ethyl alcohol (40 mL) was refluxed for 2–5 h
under dry conditions. Excess alcohol was distilled off
© 2005 NRC Canada

Chatterjee et al.
1167
under reduced pressure, water was poured into the flask,
(2H, m, CH2CH3), 3.69 (1H, s, =CHCN), 4.55 (1H, bs,
-NH). 13C NMR (CDCl3, ppm) δ: 13.17, 19.79, 38.37, 58.69,
122.53, 160.39. MS m/z: 110 (M+). Anal. calcd. for C6H10N2
(%): C 65.42, H 9.15, N 25.43; found: C 65.46, H 9.12, N
25.47.
and the contents were extracted with a suitable organic
solvent. The organic layer was first washed with 2 N
HCl, then with brine until neutral, it was then dried over
anhydr. Na2SO4 and evaporated to dryness. Recrystalli-
zation of the crude product from a suitable solvent fur-
nished the pure compound.
2c
UV (λmax, EtOH, nm): 259 (⑀ = 1.93 × 104). IR (KBr, cm–1):
(b) A mixture of chiral amine (5 mmol), thionyl chloride
(10 mmol), and dry methanol (15 mL) was refluxed for
2.5 h. Excess methanol and thionyl chloride were re-
moved under reduced pressure and the residue was dried
under vacuum. A solution of 1 (5 mmol) in dry ethyl al-
cohol (20 mL) was added to the residue with stirring at
0 °C followed by addition of triethylamine (5 mmol) in
dry ethyl alcohol (5 mL). The reaction mixture was
refluxed for 3 h. Following the usual work-up, purifica-
tion of the crude product by column chromatography on
silica gel (100–200 mesh) with 30% ethyl acetate – hex-
ane as eluent afforded the product as a thick liquid.
1
3389, 2927, 2196, 1600, 1451. H NMR (CDCl3, ppm) δ:
2.01 (3H, s, -CH3), 2.94 (2H, q, J = 5.6 Hz, -NHCH2-), 3.49
(2H, q, J = 5.6 Hz, -CH2OH), 3.78 (1H, s, =CHCN), 4.73
(1H, t, J = 5.6 Hz, -CH2OH), 6.88 (1H, bs, -NH). 13C NMR
(CDCl3, ppm) δ: 19.67, 45.90, 57.56, 58.77, 122.93, 161.18.
MS m/z: 126 (M+). Anal. calcd. for C6H10N2O (%): C 57.12,
H 7.99, N 22.21; found: C 57.15, H 7.94, N 22.25.
2d
UV (λmax, EtOH, nm): 263 (⑀ = 1.95 × 104). IR (KBr, cm–1):
1
3307, 3073, 2931, 2855, 2185, 1595, 1548, 1446. H NMR
(CDCl3, ppm) δ: 1.13–1.94 (10H, com, H atoms of cyclo-
hexane ring), 2.08 (3H, s, =CCH3), 3.05 (1H, tq, J = 4, 9 Hz,
proton of cyclohexane ring α to NH), 3.79 (1H, s, =CHCN),
4.33 (1H, bs, -NH). 13C NMR (CDCl3, ppm) δ: 20.59, 24.54,
25.19, 32.05, 34.28, 51.72, 52.09, 59.65, 122.34, 158.67.
MS m/z: 164 (M+). Anal. calcd. for C10H16N2 (%): C 73.12,
H 9.82, N 17.06; found: C 73.17, H 9.78, N 17.10.
Acylation reaction of N-benzyl-␤-aminocrotononitrile
with acid chlorides
The acid chloride (5 mmol) in dry benzene (10 mL) was
added dropwise under ice cold conditions to a magnetically
stirred solution of 2f (5 mmol) in dry benzene (50 mL) and
pyridine (15 mmol). Upon completion of the addition, stir-
ring was continued for an additional 1 h at room tempera-
ture, and then refluxed for 3–5 h. The reaction mixture was
then poured on ice water, acidified with HCl (2 N) followed
by extraction with ethyl acetate (3 × 25 mL). The organic
layer was then washed with a 5% NaHCO3 solution fol-
lowed by brine and then dried over anhydr. Na2SO4. Re-
moval of the solvent afforded solid materials, which on
crystallization furnished pure acylated products.
2e
UV (λmax, EtOH, nm): 255 (⑀ = 2.00 × 104). IR (KBr, cm–1):
3399, 3377, 3056, 2995, 2912, 2189, 1731, 1600, 1526,
1474, 1408. H NMR (CDCl3, ppm) δ: 1.09 (3H, t, J =
1
7.1 Hz, -CH2CH3), 1.96 (3H, s, =CCH3), 3.53 (1H, s, =CHCN),
3.57 (2H, d, J = 5.1 Hz, -NHCH2-), 4.05 (2H, q, -CH2CH3),
5.42 (1H, bs, -NH). 13C NMR (CDCl3, ppm) δ: 13.53, 19.14,
44.24, 60.73, 61.20, 120.92, 159.64, 168.59. MS m/z: 168
(M+). Anal. calcd. for C8H12N2O2 (%): C 57.12, H 7.19, N
16.65; found: C 57.15, H 7.25, N 16.63.
Preparation of pyrazoles
A mixture of α-cyanoenaminone (3 mmol) and phenyl
hydrazine reagent (23) (9 mmol) was heated on a steam bath
for 20–45 min, during which a yellow oily material sepa-
rated. The reaction mixture was acidified with acetic acid
(50%) followed by neutralization with solid NaHCO3. It was
then extracted with diethyl ether or ethyl acetate (3 ×
20 mL). The organic layer was washed with brine and dried
over anhydr. Na2SO4. The crude material obtained on re-
moval of the solvent was purified by crystallization from a
suitable solvent or by column chromatography (silica gel,
60–120 mesh, 5% ethyl acetate – petroleum ether).
2f
UV (λmax, EtOH, nm): 272 (⑀ = 2.30 × 104). IR (KBr, cm–1):
3304, 3088, 2192, 1594, 1560, 1492, 1446. 1H NMR
(CDCl3, ppm) δ: 2.13 (3H, s, -CH3), 3.86 (1H, s, =CHCN),
4.13 (2H, d, J = 5.02 Hz, -CH2Ph), 4.64 (1H, bs, -NH),
7.25–7.38 (5H, m, Ar-H). 13C NMR (CDCl3, ppm) δ: 20.12,
47.46, 60.83, 121.71, 127.56, 127.90, 129.32, 136.40,
159.87. MS m/z: 172 (M+). Anal. calcd. for C11H12N2 (%): C
76.71, H 7.02, N 16.27; found: C 76.75, H 6.97, N 16.30.
2g
Spectral data of prepared compounds 2a–2p
UV (λmax, EtOH, nm): 288 (⑀ = 1.61 × 104). IR (KBr, cm–1):
3266, 3125, 3058, 2199, 1612, 1586, 1542. 1H NMR
(CDCl3, ppm) δ: 2.24 (3H, s, =CCH3), 4.40 (1H, s,
=CHCN), 6.13 (1H, bs, -NH), 7.12–7.38 (5H, m, Ar-H). 13C
NMR (CDCl3, ppm) δ: 20.50, 64.88, 121.26, 123.85, 125.67,
129.51, 138.46, 158.29. MS m/z: 158 (M+). Anal. calcd. for
C10H10N2 (%): C 75.92, H 6.37, N 17.71; found: C 75.96, H
6.42, N 17.67.
2a
UV (λmax, EtOH, nm): 260 (⑀ = 1.97 × 104). IR (KBr, cm–1):
1
3336, 2925, 2188, 1603, 1545. H NMR (CDCl3, ppm) δ:
2.12 (3H, s, =C-CH3), 2.72 (3H, d, J = 5.9 Hz, NHCH3),
3.75 (1H, s, =CHCN), 5.21 (1H, bs, -NH). MS m/z: 96 (M+).
Anal. calcd. for C5H8N2 (%): C 62.47, H 8.39, N 29.14;
found: C 62.50, H 8.36, N 29.19.
2h
2b
UV (λmax, EtOH, nm): 259 (⑀ = 2.08 × 104). IR (KBr, cm–1):
UV (λmax, EtOH, nm): 284 (⑀ = 1.61 × 104). IR (KBr, cm–1):
1
1
3329, 2188, 1601, 1544, 1458. H NMR (CDCl3, ppm) δ:
1.16 (3H, t, J = 7.18 Hz, -CH2CH3), 2.04 (3H, s, CH3), 2.93
3304, 3278, 2191, 1605, 1514. H NMR (CDCl3, ppm) δ:
2.22 (3H, s, =CCH3), 3.80 (3H, s, -OCH3), 4.12 (1H, s,
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Can. J. Chem. Vol. 83, 2005
=CHCN), 5.94 (1H, bs, -NH), 6.88 and 7.06 (each 2H, d, J =
8.2 Hz, Ar-H). 13C NMR (CDCl3, ppm) δ: 20.21, 55.44,
63.73, 82.14, 114.32, 121.58, 126.52, 131.0, 157.81, 159.54.
MS m/z: 188 (M+). Anal. calcd. for C11H12N2O (%): C
70.19, H 6.43, N 14.88; found: C 70.24, H 6.39, N 14.91.
2n
UV (λmax, CHCl3, nm): 256 (⑀ = 1.68 × 104). IR (as
oil, cm–1): 3319, 3074, 2957, 2871, 2198, 1739, 1604, 1543,
1437. H NMR (CDCl3, ppm) δ: 0.83 (3H, d, J = 6.2 Hz,
1
-CHCH3), 0.87 (3H, d, J = 6.2 Hz, -CHCH3), 1.53–1.63 (3H,
com, -CH2-CHMe2), 2.04 (3H, s, =CCH3), 3.66 (3H, s,
-CO2CH3), 3.71 (1H, s, =CHCN), 3.75 (1H, q, J = 7.3 Hz,
-CHCO2CH3), 5.12 (1H, d, J = 7.6 Hz, -NH). 13C NMR
(CDCl3, ppm) δ: 19.75, 21.75, 22.22, 24.54, 41.65, 52.82,
54.95, 62.07, 120.92, 159.69, 172.81. MS m/z: 210 (M+).
Anal. calcd. for C11H18N2O2 (%): C 62.83, H 8.63, N 13.32;
found: C 62.90, H 8.70, N 13.38.
2i
UV (λmax, EtOH, nm): 293 (⑀ = 1.93 × 104). IR (KBr, cm–1):
1
3276, 2190, 1580, 1521, 1438. H NMR (CDCl3, ppm) δ:
2.20 (3H, s, =CCH3), 2.24 (3H, s, -o-CH3 C6H4), 3.81
(1H, s, =CHCN), 5.82 (1H, bs, -NH), 7.10–7.23 (4H, m, Ar-
H). 13C NMR (CDCl3, ppm) δ: 17.18, 19.75, 63.89, 119.00,
126.41, 126.55, 126.67, 126.80, 126.97, 130.99, 159.90. MS
m/z: 172 (M+). Anal. calcd. for C11H12N2 (%): C 76.75, H
7.02, N 16.27; found: C 76.79, H 6.93, N 16.21.
2o
UV (λmax, CHCl3, nm): 258 (⑀ = 2.41 × 104). IR (as
oil, cm–1): 3318, 3029, 3066, 2953, 2198, 1740, 1604, 1541,
1
1438. H NMR (CDCl3, ppm) δ: 2.09 (3H, s, =CCH3), 3.03
2j
(1H, dd, J = 5.76, 13.57 Hz, -CH2Ph), 3.73 (3H, s, -CO2CH3),
3.84 (1H, s, =CHCN), 4.16 (1H, dt, J = 5.76, 6.33 Hz,
-CHCH2-), 4.77 (1H, bd, J = 6.33 Hz, -NH), 7.05–7.33
(5H, m, Ar-H). 13C NMR (CDCl3, ppm) δ: 20.03, 36.80,
52.50, 56.30, 61.80, 63.00, 120.70, 127.40, 128.60, 129.00,
134.90, 158.30, 171.30. MS m/z: 245 (MH+). Anal. calcd.
for C14H16N2O2 (%): C 68.83, H 6.60, N 11.46; found: C
68.93, H 6.65, N 11.41.
UV (λmax, EtOH, nm): 294 (⑀ = 1.94 × 104). IR (KBr, cm–1):
1
3312, 2184, 1598, 1548, 1310. H NMR (CDCl3, ppm) δ:
2.21 (3H, s, =CCH3), 2.32 (3H, s, p-CH3 C6H4), 4.28 (1H, s,
=CHCN), 5.96 (1H, bs, -NH), 6.99 and 7.14 (each 2H, d, J =
8.2 Hz, Ar-H). MS m/z: 172 (M+, 100). Anal. calcd. for
C11H12N2 (%): C 76.75, H 7.02, N 16.27; found: C 76.81, H
7.09, N 16.32.
2p
2k
UV (λmax, CHCl3, nm): 258 (⑀ = 1.81 × 104). IR (as
UV (λmax, EtOH, nm): 258 (⑀ = 2.10 × 104). IR (KBr, cm–1):
3301, 3061, 2190, 1596, 1545, 1446, 1382. 1H NMR
(CDCl3, ppm) δ: 1.45 (3H, d, J = 6.7 Hz, -CHCH3), 2.11
(3H, s, -CH3), 3.61 (1H, s, =CHCN), 4.28 (1H, m, J =
6.71 Hz, -CH-CH3), 4.73 (1H, bs, -NH), 7.18–7.34 (5H, m,
Ar-H). 13C NMR (CDCl3, ppm) δ: 20.54, 23.94, 53.61,
63.08, 121.79, 125.49, 125.67, 129.06, 142.61, 158.80. MS
m/z: 186 (M+). Anal. calcd. for C12H14N2 (%): C 77.38, H
7.57, N 15.05; found: C 77.42, H 7.46, N 15.09.
oil, cm–1): 3318, 3074, 2976, 2871, 2199, 1739, 1604, 1516,
1442. H NMR (CDCl3, ppm) δ: 2.09 (3H, s, =CCH3), 2.96
1
(1H, dd, J = 5.5, 13.8 Hz, -CH2), 3.08 (1H, dd, J = 5.8,
13.8 Hz, -CH2), 3.74 (3H, s, -CO2CH3), 3.83 (1H, s,
=CHCN), 4.07–4.15 (1H, com, -CH-), 4.78 (1H, bd, J =
6.8 Hz, -NH), 5.98 (1H, bs, -OH), 6.77 and 6.92 (each 2H,
d, J = 8.3 Hz, Ar-H). 13C NMR (CDCl3, ppm) δ: 20.28,
36.14, 52.65, 56.76, 62.07, 111.65, 121.23, 126.36, 130.25,
145.15, 155.60, 159.34, 171.78. MS m/z: 260 (M+). Anal.
calcd. for C14H16N2O3 (%): C 64.60, H 6.19, N 10.76;
found: C 64.72, H 6.26, N 10.71.
2l
UV (λmax, CHCl3, nm): 257 (⑀ = 1.60 × 104). IR (as
oil, cm–1): 3322, 3076, 2956, 2850, 2199, 1740, 1607, 1546,
Spectral data of prepared compounds 3a–3e
1
1454. H NMR (CDCl3, ppm) δ: 1.43 (3H, d, J = 6.9 Hz,
-CHCH3), 2.13 (3H, s, =CCH3), 3.77 (1H, s, =CHCN), 3.78
(3H, s, -CO2CH3), 3.92 (1H, quintet, J = 7 Hz, -CHCO2CH3),
4.90 (1H, bs, -NH). 13C NMR (CDCl3, ppm) δ: 18.04, 20.78,
51.79, 53.14, 62.87, 121.36, 159.00, 173.33. MS m/z: 168
(M+). Anal. calcd. for C8H12N2O2 (%): C 57.12, H 7.19, N
16.65; found: C 56.97, H 7.13, N 16.51.
3a
UV (λmax, EtOH, nm): 321 (⑀ = 1.85 × 104). IR (KBr, cm–1):
1
2198, 1608, 1465, 1321. H NMR (CDCl3, ppm) δ: 2.40
(3H, s, CH3), 4.62 (2H, d, J = 5.9 Hz, CH2Ph), 7.21–7.79
(10H, m, Ar-H), 12.66 (1H, bs, NH). 13C NMR (CDCl3,
ppm) δ: 18.1, 48.2, 82.5, 121.3, 127.0, 127.7, 128.0, 128.3,
129.2, 131.2, 135.2, 139.1, 172.1, 192.6. MS m/z: 276 (M+).
Anal. calcd. for C18H16N2O (%): C 78.24, H 5.84, N 10.14;
found: C 78.29, H 5.81, N 10.16.
2m
UV (λmax, CHCl3, nm): 256 (⑀ = 1.65 × 104). IR (as
oil, cm–1): 3332, 3074, 2966, 2877, 2197, 1738, 1604, 1541,
1436. H NMR (CDCl3, ppm) δ: 0.94 (3H, d, J = 6.75 Hz,
1
3b
-CH3), 1.0 (3H, d, J = 6.75 Hz, -CH3), 2.08–2.13 (1H, com,
CHMe2), 2.15 (3H, s, =CCH3), 3.64 (1H, q, J = 5.8 Hz,
-CHCOOCH3), 3.76 (3H, s, -CO2CH3), 3.81 (1H, s,
=CHCN), 4.86 (1H, d, J = 7.2 Hz, -NH). 13C NMR (CDCl3,
ppm) δ: 17.81, 18.60, 30.83, 31.75, 52.21, 61.36, 63.12,
120.99, 159.42, 171.85. MS m/z: 196 (M+). Anal. calcd. for
C10H16N2O2 (%): C 61.20, H 8.22, N 14.27; found: C 61.24,
H 8.29, N 14.22.
UV (λmax, EtOH, nm): 310 (⑀ = 1.63 × 104). IR (KBr, cm–1):
1
2199, 1605, 1584, 1473, 1316. H NMR (CDCl3, ppm) δ:
2.39 (3H, s, CH3), 4.64 (2H, d, J = 6.2 Hz, CH2Ph), 7.0–
8.22 (9H, m, Ar-H), 11.97 (1H, bs, NH). 13C NMR (CDCl3,
ppm) δ: 18.5, 48.6, 84.1, 120.0, 124.8, 127.3, 128.7, 128.8,
129.6, 130.6, 134.3, 135.3, 136.2, 146.1, 171.9, 190.7. MS
m/z: 321 (M+). Anal. calcd. for C18H15N3O3 (%): C 67.28, H
4.71, N 13.08; found: C 67.33, H 4.69, N 13.11.
© 2005 NRC Canada

Chatterjee et al.
1169
3c
5d
UV (λmax, EtOH, nm): 237 (⑀ = 0.59 × 104), 249 (⑀ =
UV (λmax, EtOH, nm): 324 (⑀ = 2.08 × 104). IR (KBr, cm–1):
1.22 × 104). IR (KBr, cm–1): 2221, 1593, 1545, 1513, 1456,
1
2200, 1601, 1528, 1461, 1317. H NMR (CDCl3, ppm) δ:
1
1416. H NMR (CDCl3, ppm) δ: 2.48 (3H, s, CH3), 6.90–
2.43 (3H, s, CH3), 4.67 (2H, d, J = 5.9 Hz, CH2Ph), 7.28–
7.42 (5H, m, CH2Ph), 7.60 (1H, t, J = 7.9 Hz, 5-H of m-
NO2-Ph ring), 8.12 (1H, d, J = 7.8 Hz, 6-H of m-NO2-Ph
ring), 8.30 (1H, d, J = 7.8 Hz, 4-H of m-NO2-Ph ring), 8.60
(1H, s, 2-H of m-NO2-Ph ring), 12.57 (1H, bs, NH). 13C
NMR (CDCl3, ppm) δ: 18.4, 48.6, 82.6, 120.7, 123.3, 125.7,
127.4, 128.7, 129.3, 129.5, 133.6, 134.9, 140.6, 148.1,
172.8, 189.6. MS m/z: 321 (M+). Anal. calcd. for
C18H15N3O3 (%): C 67.28, H 4.71, N 13.08; found: C 67.32,
H 4.72, N 13.10.
7.90 (8H, m, Ar-H). MS m/z: 265 (M+). Anal. calcd. for
C15H11N3S (%): C 67.91, H 4.18, N 15.84; found: C 67.95,
H 4.20, N 15.88.
5e
UV (λmax, EtOH, nm): 255 (⑀ = 1.51 × 104). IR (KBr, cm–1):
1
2222, 1595, 1545, 1513, 1460. H NMR (CDCl3, ppm) δ:
1.38 (6H, d, J = 7.2 Hz, (CH3)2), 2.40 (3H, s, CH3), 3.07
(1H, heptet, J = 7.2 Hz, CH(CH3)2), 7.32–7.52 (5H, m, Ar-
H). 13C NMR (CDCl3, ppm) δ: 12.31, 18.94, 21.43, 89.85,
114.40, 126.09, 128.22, 129.15, 138.30, 152.62, 155.57. MS
m/z: 225 (M+). Anal. calcd. for C14H15N3 (%): C 74.64, H
6.71, N 18.65; found: C 74.69, H 6.69, N 18.63.
3d
UV (λmax, EtOH, nm): 340 (⑀ = 1.96 × 104), 249 (⑀ =
1.22 × 104). IR (KBr, cm–1): 2195, 1619, 1601, 1544, 1511,
1453. H NMR (CDCl3, ppm) δ: 2.38 (3H, s, CH3), 4.61
1
(2H, d, J = 5.8 Hz, CH2Ph), 7.0–8.25 (8H, m, Ar-H), 12.45
(1H, bs, NH). MS m/z: 282 (M+). Anal. calcd. for
C16H14N2OS (%): C 68.07, H 4.99, N 9.92; found: C 68.09,
H 4.96, N 9.95.
Acknowledgements
The authors are indebted to Dr. V.A. Snieckus, Queen’s
University, Kingston, Ontario and Dr. W. Froestl, Novartis
Pharma AG, Basel, Switzerland for recording the NMR and
MS spectra of some of the compounds. MM thanks Jadavpur
University for a Senior Research Fellowship.
3e
UV (λmax, EtOH, nm): 304 (⑀ = 1.58 × 104). IR (KBr, cm–1):
1
2192, 1623, 1574, 1468. H NMR (CDCl3, ppm) δ: 1.07
(3H, d, J = 7.1 Hz, CH(CH3)CH3), 1.14 (3H, d, J = 7.1 Hz,
CH(CH3)CH3), 2.30 (3H, s, CH3), 3.14 (1H, m, CH(CH3)2),
4.54 (2H, d, J = 6.1 Hz, CH2Ph), 7.34 (5H, m, Ar-H), 12.26
(1H, bs, NH). 13C NMR (CDCl3, ppm) δ: 18.0, 19.1, 31.0,
37.8, 48.2, 82.6, 121.0, 127.2, 128.4, 129.3, 135.5, 170.8,
203.3. MS m/z: 242 (M+). Anal. calcd. for C15H18N2O (%):
C 74.34, H 7.49, N 11.56; found: C 74.30, H 7.52, N 11.58.
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Spectral data of prepared compounds 5a–5e
5a
UV (λmax, EtOH, nm): 255 (⑀ = 1.14 × 104). IR (KBr, cm–1):
2220, 1593, 1538, 1504, 1450, 1424, 1137. 1H NMR
(CDCl3, ppm) δ: 2.50 (3H, s, CH3), 7.24–7.52 (10H, m, Ar-
H). MS m/z: 259 (M+). Anal. calcd. for C17H13N3 (%): C
78.74, H 5.05, N 16.20; found: C 78.79, H 5.02, N 16.23.
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5b
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UV (λmax, EtOH, nm): 246 (⑀ = 1.39 × 104). IR (KBr, cm–1):
1
2228, 1595, 1528, 1502, 1445. H NMR (CDCl3, ppm) δ:
2.54 (3H, s, CH3), 7.0–8.06 (9H, m, Ar-H). MS m/z: 304
(M+). Anal. calcd. for C17H12N4O2 (%): C 67.10, H 3.97, N
18.41; found: C 67.18, H 3.95, N 18.45.
5c
UV (λmax, EtOH, nm): 254 (⑀ = 1.57 × 104). IR (KBr, cm–1):
2227, 1596, 1526, 1501, 1429, 1387, 1348. 1H NMR
(CDCl3, ppm) δ: 2.53 (3H, s, CH3), 7.22–8.28 (9H, m, Ar-
H). 13C NMR (CDCl3, ppm) δ: 12.54, 94.60, 113.4, 123.93,
124.55, 125.30, 128.78, 129.16, 129.53, 130.21, 134.64,
138.02, 145.02, 148.36, 152.95. MS m/z: 304 (M+). Anal.
calcd. for C17H12N4O2 (%): C 67.10, H 3.97, N 18.41;
found: C 67.17, H 3.99, N 18.44.
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1170
Can. J. Chem. Vol. 83, 2005
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© 2005 NRC Canada