Indium(III) iodide-mediated Strecker reaction in water: an efficient and environmentally friendly approach for the synthesis of α-aminonitrile via a three-component condensation

Article abstract of DOI:10.1016/j.tet.2008.06.047

A mild, efficient and environmentally friendly method has been developed for the synthesis of α-aminonitriles via a three-component condensation of aldehyde, amine and TMSCN in the presence of a catalytic amount of indium(III) iodide in water. The reactions proceeded smoothly at room temperature in water to generate the corresponding products in moderate to excellent yields.

Full text of DOI:10.1016/j.tet.2008.06.047

Tetrahedron 64 (2008) 8159–8163
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Tetrahedron
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Indium(III) iodide-mediated Strecker reaction in water: an efficient and
environmentally friendly approach for the synthesis of
via a three-component condensation
a-aminonitrile
,
,
a,
*
Zhi-Liang Shen a b, Shun-Jun Ji b , Teck-Peng Loh
*
a Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
b Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering, Suzhou (Soochow) University, Suzhou 215123, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 15 April 2008
Received in revised form 8 June 2008
Accepted 13 June 2008
Available online 19 June 2008
A mild, efficient and environmentally friendly method has been developed for the synthesis of a-ami-
nonitriles via a three-component condensation of aldehyde, amine and TMSCN in the presence of
a catalytic amount of indium(III) iodide in water. The reactions proceeded smoothly at room temperature
in water to generate the corresponding products in moderate to excellent yields.
Ó 2008 Published by Elsevier Ltd.
Keywords:
Strecker reaction
a
-Aminonitrile
Indium(III) iodide
Water
Three-component reaction
1. Introduction
dedicated to developing organic reactions in water with many in-
herent advantages over reactions in conventional organic solvents.
a
-Aminonitriles are significantly important intermediates for
Therefore, if the Strecker reaction can be developed to operate in
water, it will be of practical value and contribute to the area of
water chemistry.
the synthesis of a wide variety of amino acids, amides, diamines
and nitrogen-containing heterocycles.1 Among the methods
reported for the synthesis of
which proceeded via the addition of HCN to imine proved to be an
effective one for the preparation of
-aminonitrile.2 Recently,
a
-aminonitriles, Strecker reaction,
More recently, indium(III) compounds have been demonstrated
to be mild, efficient and water-tolerant Lewis acids for various
organic transformations.5 In contrast to classical Lewis acids, which
often are required in stoichiometric quantities, indium(III) com-
pounds readily promote a wide variety of organic reactions in cat-
alytic quantities soluble both in organic solvents and in aqueous
media. In continuationof ourwork toapply indium(III) compoundas
catalyst to organic reactions in water,6 herein, we report an efficient
a
modified method using one-pot procedure via a three-component
condensation of aldehyde, amine and trimethylsilyl cyanide
(TMSCN, a promising alternative to HCN and alkali cyanide due to
its nature as an effective, safe and easily-handled cyanation reagent)
catalyzed by Lewis acids (or protic acids) in conventional organic
solvents has been described.3 However, many of these reported
methods involve the use of expensive reagents, toxic organic
solvent, tedious workup procedure and longer reaction times.
Therefore, it is still desirable to develop an efficient and practical
method for the Strecker reaction under mild conditions.
and environmentally friendly method for the synthesis of a-ami-
nonitriles catalyzed by indium(III) iodide (InI3) in water (Scheme 1).
CN
O
InI3 (10 mol%)
H2O, r.t.
R'
R' NH2
TMSCN
+
+
R
N
H
R
H
In recent decades, water has aroused considerable attention in
synthetic community and proved to be a promising solvent in or-
ganic synthesis due to its economic, environmentally friendly and
polar nature.4 In relation to this, significant efforts have been
Scheme 1. Strecker reaction in water.
2. Results and discussion
Initial research was focused on the reaction of benzaldehyde,
aniline and TMSCN in acetonitrile using different catalysts
(10 mol %). As shown in Table 1, the one-pot reaction proceeded
* Corresponding authors. Tel.: þ65 6316 8899; fax: þ65 6791 1961.
E-mail address: teckpeng@ntu.edu.sg (T.-P. Loh).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.06.047

8160
Z.-L. Shen et al. / Tetrahedron 64 (2008) 8159–8163
Table 1
One-pot synthesis of
Table 2
One-pot synthesis of
a
-aminonitrile using different catalysts
a
-aminonitrile in watera
O
CN
CN
NH2
O
InI3 (10 mol%)
H2O, r.t., 0.5 h
NH2
catalyst (10 mol%)
TMSCN
+
+
TMSCN
+
+
H
N
N
R
R
H
solvent, r.t.
H
H
Entry
Aldehyde
Yieldb (%)
91
Entry
Catalyst
Solvent
Time
Yielda (%)
O
1
2
3
4
5
6
7
8
InF3
InCl3
InBr3
In(OTf)3
In(OH)3
InI3
InI3
InI3
Pyridine
DABCOd
DMAPe
HMTf
MIMg
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
db
24 h
24 h
24 h
24 h
24 h
24 h
10 min
30 min
24 h
24 h
24 h
24 h
24 h
94
93
91
93
72
98
95
1
2
3
H
Cl
O
95
90
H
H2O
95 (89)c
87
89
76
67
9
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
O
10
11
12
13
H
87
O
a
Isolated yield.
b
c
d
e
f
4
93
H
Solvent-free condition.
With catalyst loading of 5 mol %.
MeO
DABCO¼1,8-diazabicyclo[5.4.0]undec-7-ene.
DMAP¼4-N,N-dimethylamino pyridine.
HMT¼hexamethylenetetramine.
O
5
6
7
93
92
81
H
g
MIM¼1-methyl imidazole.
OMe
O
efficiently in the presence of various indium(III) compounds at
room temperature. Among the various catalysts used, InI3 proved to
be the best one and 98% yield of the corresponding product was
afforded (entry 6, Table 1). In the meantime, employing InI3 as
catalyst, it was found that the three-component reaction could also
take place efficiently in water or under solvent-free condition to
furnish the desired product both in 95% yields within a short
reaction time of 30 min (entries 7 and 8, Table 1). Considering the
advantages provided by using water as reaction solvent, following
reactions were carried out in water. In addition, it was worthy of
noting that the one-pot reaction could also work well in acetonitrile
in the presence of different nitrogen-containing organocatalysts,
good yields were obtained when utilizing pyridine, 1,8-dia-
zabicyclo[5.4.0]undec-7-ene (DABCO) and 1-methyl imidazole
(MIM) as catalysts (entries 9, 10 and 13, Table 1).
H
O
H
O
8
9
93
97
H
O
O
O
H
H
S
10
83
N
In the following work, a series of a-aminonitriles were synthe-
a
sized by using different aldehydes, amines and TMSCN in the
presence of InI3 (10 mol %) in water. As shown in Table 2, all
aldehydes could react effectively with aniline and TMSCN in water
catalyzed by InI3 to afford the corresponding products with ex-
cellent yields of 81–97%. The catalytic system also worked well with
acid sensitive heterocyclic aldehydes such as 5-methyl-fur-
aldehyde, 2-thiophenecarboxaldehyde and 3-pyridinecarbox-
aldehyde to generate the corresponding products with good yields
The reactions were operated at room temperature for 0.5 h catalyzed by InI3 in
water.
b
Isolated yield.
The three-component condensation is proposed to proceed via
two-step reactions. Firstly, InI3 serves as a Lewis acid to promote
the formation of imine, which derived from the condensation of
aldehyde and amine. Then the formed imine is further activated by
InI3 to produce a more electrophilic C]N intermediate, which
facilitates the following attack of TMSCN to the carbon–nitrogen
of 93%, 97% and 83% (entries 8, 9 and 10, Table 2). Even for a,b-
unsaturated aldehyde, a good yield of the desired product (81%)
was obtained without observing the formation of other side
products (Table 2, entry 7).
double bond, and thus forms the desired product
after hydrolysis with water.
a-aminonitrile
Encouraged by above results, we continued our task to explore
the reactivity of different amines with benzaldehyde and TMSCN
under similar reaction conditions. As shown in Table 3, all aromatic
amines could efficiently undergo reactions with benzaldehyde and
TMSCN to give the products in excellent yields (entries 1–4, Table
3). When it came to aliphatic amines such as benzyl amine, pyr-
rolidine and morpholine, relatively slow reaction rate occurred due
to the unstable nature of the formed aliphatic imines in the pres-
ence of water (entries 5–7, Table 3). However, if the reaction time
was prolonged to 10 h, moderate to good yields of the desired
products could be obtained.
3. Conclusion
In summary, we have developed a mild, efficient and environ-
mentally friendly method for the synthesis of -aminonitriles via
a
a three-component condensation of aldehydes, amines and TMSCN
catalyzed by a catalytic amount of water-stable Lewis acid InI3 in
water. This method is quite general and it works well with a wide
variety of aldehydes and amines at room temperature. The mild
reaction conditions, short reaction time, good yields, the simplicity

Z.-L. Shen et al. / Tetrahedron 64 (2008) 8159–8163
8161
Table 3
and InI3 (0.1 mmol) sequentially. The reaction was stirred vigor-
ously at room temperature and the progress of the reaction was
monitored by TLC. After stirring for a special time as shown in
Tables 2 and 3, the reaction system was extracted by diethyl ether
(15 mLꢀ3), washed with brine. Following dry over anhydrous
MgSO4, removal of the solvent and passage through a column of
One-pot synthesis of
a
-aminonitrile via
a
three-component condensation of
benzaldehyde, TMSCN and various aminesa
O
CN
InI3 (10 mol%)
H2O, r.t.
R
R
NH2
TMSCN
+
+
H
N
H
silica gel gave the desired product a-aminonitriles.
Entry
1
Amine
Time (h)
Yieldb (%)
91
4.2.1. 2-(N-Anilino)-2-(4-chlorophenyl)acetonitrile
(Table 2, entry 1)
NH2
0.5
Rf¼0.61 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n 3381,
Cl
Br
2236 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
4.10 (d, J¼8.43 Hz, 1H),
NH2
NH2
5.36 (d, J¼8.43 Hz, 1H), 6.72 (d, J¼7.65 Hz, 2H), 6.88 (t, J¼7.43 Hz,
1H), 7.24 (t, J¼7.83 Hz, 2H), 7.37 (d, J¼8.43 Hz, 2H), 7.47 (d,
2
3
1
1
90
82
J¼8.22 Hz, 2H) ppm; 13C NMR (75.4 MHz, CDCl3):
d 144.4 (C), 135.4
(C),132.4 (C),129.5 (CHꢀ2),129.4 (CHꢀ2),128.5 (CHꢀ2),120.4 (CH),
117.9 (CN), 114.3 (CHꢀ2), 49.5 (CH) ppm; HRMS (EI, m/z): [M]þ,
Calcd for C14H11ClN2: 242.0611, found: 242.0602.
NH2
4
0.5
86
4.2.2. 2-(N-Anilino)-2-phenylacetonitrile (Table 2, entry 2)
Rf¼0.23 (ethyl acetate/hexane¼1:6); FTIR (NaCl, neat):
n 3369,
4.03 (d, J¼8.34 Hz, 1H),
NH2
2235 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
5
6
10
81
73
5.42 (d, J¼8.34 Hz, 1H), 6.77 (d, J¼7.65 Hz, 2H), 6.90 (t, J¼7.32 Hz,
1H), 7.29 (m, 2H), 7.46 (m, 3H), 7.59 (m, 2H) ppm; 13C NMR
10
10
(75.4 MHz, CDCl3):
d
50.3 (CH), 114.2 (CHꢀ2), 118.2 (CN), 120.3 (CH),
N
H
O
127.3 (CHꢀ2), 129.3 (CHꢀ2), 129.5 (CH), 129.6 (CHꢀ2), 134.0 (CH),
144.7 (CH) ppm; HRMS (EI, m/z): [M]þ, Calcd for C14H12N2:
208.1000, found: 208.0996.
7
78
N
H
a
4.2.3. 2-(N-Anilino)-2-(4-methylphenyl)acetonitrile
(Table 2, entry 3)
The reactions were operated at room temperature catalyzed by InI3 in water.
Isolated yield.
b
Rf¼0.56 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n 3339,
2.45 (s, 3H), 4.15 (d,
2235 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
of the reaction procedure and environmentally friendly feature
make this method attractive for scale-up purposes.
J¼8.04 Hz, 1H), 5.40 (d, J¼8.01 Hz, 1H), 6.81 (d, J¼8.43 Hz, 2H), 6.95
(m, 1H), 7.28–7.35 (m, 4H), 7.51 (d, J¼8.04 Hz, 2H) ppm; 13C NMR
(75.4 MHz, CDCl3):
129.4 (CHꢀ2), 127.0 (CHꢀ2), 119.9 (CH), 118.3 (CN), 114.0 (CHꢀ2),
d
144.7 (C), 139.3 (C), 130.9 (C), 129.8 (CHꢀ2),
4. Experimental
49.7 (CH), 21.0 (CH3) ppm; HRMS (EI, m/z): [M]þ, Calcd for
4.1. General method
C15H14N2: 222.1157, found: 222.1158.
Analytical thin layer chromatography (TLC) was performed us-
ing Merck 60 F254 precoated silica gel plate (0.2 mm thickness).
Subsequent to elution, plates were visualized using UV radiation
(254 nm) on Spectroline Model ENF-24061/F 254 nm. Further
visualization was possible by staining with acidic solution of ceric
molybdate or ethanolic solution of ninhydrin. Flash-column chro-
matography was performed using Merck silica gel 60 with freshly
distilled solvents. 1H NMR and 13C NMR spectra were recorded on
a Bruker Avance DPX 300 and Bruker AMX 400 spectrophotometers
using TMS as an internal standard. Chemical shifts for 1H NMR
4.2.4. 2-(N-Anilino)-2-(4-methoxyphenyl)acetonitrile
(Table 2, entry 4)
Rf¼0.59 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n 3361,
2234 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 3.84 (s, 3H), 4.15 (d,
J¼8.43 Hz, 1H), 5.36 (d, J¼8.04 Hz, 1H), 6.79 (d, J¼8.43 Hz, 2H),
6.90–6.99 (m, 3H), 7.29 (t, J¼8.03 Hz, 2H), 7.50 (d, J¼8.01 Hz,
2H) ppm; 13C NMR (75.4 MHz, CDCl3):
d 160.2 (C), 144.7 (C), 129.4
(CHꢀ2), 128.5 (CHꢀ2), 125.8 (C), 119.9 (CH), 118.4 (CN), 114.4
(CHꢀ2), 114.0 (CHꢀ2), 55.3 (CH3), 49.4 (CH) ppm; HRMS (EI, m/z):
[M]þ, Calcd for C15H14N2O: 238.1106, found: 238.1100.
spectra are reported as
downfield from SiMe4
form-d ( 7.2600, s). Multiplicities were given as: s (singlet);
d
in units of parts per million (ppm)
(
d 0.0) and relative to the signal of chloro-
4.2.5. 2-(N-Anilino)-2-(2-methoxyphenyl)acetonitrile
(Table 2, entry 5)
d
d (doublet); t (triplet); q (quartet); or m (multiplets). The number of
protons (n) for a given resonance is indicated by nH. Coupling
constants are reported as a J value in hertz. Carbon nuclear mag-
Rf¼0.44 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
2233 cmꢁ1 1H NMR (300 MHz, CDCl3):
3.91 (s, 3H), 4.44 (d,
J¼8.82 Hz, 1H), 5.65 (d, J¼8.43 Hz, 1H), 6.83–7.08 (m, 5H), 7.29–7.54
(m, 4H) ppm;13C NMR (75.4 MHz, CDCl3):
156.6 (C),144.9 (C),130.8
(CH),129.3 (CHꢀ2),128.5 (CH),122.2 (C),121.0 (CH),119.7 (CH),118.6
(CN),114.2 (CHꢀ2),111.3 (CH), 55.6 (CH), 45.5 (CH3) ppm; HRMS (EI,
m/z): [M]þ, Calcd for C15H14N2O: 238.1106, found: 238.1104.
n 3372,
;
d
netic resonance spectra (13C NMR) are reported as
d
in units of parts
0.0) and relative to the
77.03, t). HRMS spectra were obtained
d
per million (ppm) downfield from SiMe4 (
d
signal of chloroform-d (
d
using Finnigan MAT95XP GC/HRMS (Thermo Electron Corporation).
IR spectra were recorded on a Bio-Rad FTS 165 FTIR spectrometer.
4.2.6. 2-(N-Anilino)-2-(1-naphthyl)acetonitrile (Table 2, entry 6)
4.2. Representative experimental procedure
Rf¼0.46 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n
3359,
2236 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
4.15 (d, J¼8.04 Hz, 1H),
To
a
10 mL round-bottomed flask were added aldehyde
5.96 (d, J¼8.01 Hz, 1H), 6.83 (d, J¼8.85 Hz, 2H), 6.98 (m, 1H), 7.35 (t,
(1.0 mmol), amine (1.0 mmol), TMSCN (1.2 mmol), H2O (0.5 mL)
J¼7.62 Hz, 2H), 7.50–7.60 (m, 3H), 7.92–7.97 (m, 4H) ppm; 13C NMR

8162
Z.-L. Shen et al. / Tetrahedron 64 (2008) 8159–8163
(75.4 MHz, CDCl3):
d
144.7 (C), 133.8 (C), 130.5 (CH), 130.0 (C), 129.5
4.2.13. 2-[N-(2-Methylanilino)]-2-phenylacetonitrile
(Table 3, entry 3)
Rf¼0.53 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
2236 cmꢁ1 1H NMR (300 MHz, CDCl3):
2.21 (s, 3H), 3.90 (d,
(CHꢀ2), 129.0 (CH), 128.9 (C), 127.2 (CH), 126.4 (CH), 126.1 (CH),
125.1 (CH), 122.7 (CH), 120.0 (CH), 118.2 (CN), 113.6 (CHꢀ2), 48.1
(CH) ppm; HRMS (EI, m/z): [M]þ, Calcd for C18H14N2: 258.1157,
found: 258.1157.
n
3360,
;
d
J¼8.29 Hz, 1H), 5.29 (d, J¼8.44 Hz, 1H), 6.45–6.48 (m, 2H), 6.61 (d,
J¼7.47 Hz, 1H), 7.05 (t, J¼7.58 Hz, 1H), 7.32–7.34 (m, 3H), 7.46–7.47
4.2.7. 2-(N-Anilino)-4-phenyl-butenenitrile (Table 2, entry 7)
(m, 2H) ppm; 13C NMR (75.4 MHz, CDCl3):
d 144.6 (C), 139.4 (C),
Rf¼0.55 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n
3428,
133.9 (C), 129.4 (CH), 129.3 (CH), 129.2 (CHꢀ2), 127.1 (CHꢀ2), 121.0
(CH), 118.2 (CN), 114.8 (CH), 111.2 (CH), 50.1 (CH), 21.5 (CH3) ppm;
HRMS (EI, m/z): [M]þ, Calcd for C15H14N2: 222.1157, found: 222.1151.
2225 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
3.91 (d, J¼9.24 Hz, 1H),
5.04 (m, 1H), 6.25 (dd, J¼16.05, 5.22 Hz, 1H), 6.76 (q, J¼3.21 Hz, 2H),
6.89 (t, J¼7.43 Hz, 1H), 7.03 (dd, J¼15.63, 1.59 Hz, 1H), 7.23–7.39 (m,
7H) ppm; 13C NMR (75.4 MHz, CDCl3):
d
144.5 (C), 135.1 (CH), 134.9
4.2.14. 2-[N-(1-Naphthylamino)]-2-phenylacetonitrile
(Table 3, entry 4)
(C), 129.6 (CHꢀ2), 128.9 (CH), 128.8 (CHꢀ2), 126.9 (CHꢀ2), 121.0
(CH), 120.4 (CH), 117.7 (CN), 114.4 (CHꢀ2), 47.7 (CH) ppm; HRMS (EI,
m/z): [M]þ, Calcd for C16H14N2: 234.1157, found: 234.1154.
Rf¼0.53 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
2236 cmꢁ1 1H NMR (300 MHz, CDCl3):
4.62 (d, J¼8.43 Hz, 1H),
5.47 (d, J¼8.04 Hz, 1H), 6.83 (dd, J¼6.83, 1.62 Hz, 1H), 7.32–7.80 (m,
11H) ppm; 13C NMR (75.4 MHz, CDCl3):
139.8 (C), 134.2 (C), 133.9
n 3365,
;
d
4.2.8. 2-(N-Anilino)-2-(5-methyl-2-furyl)acetonitrile
(Table 2, entry 8)
d
(C), 129.5 (CH), 129.3 (CHꢀ2), 128.7 (CH), 127.3 (CHꢀ2), 126.11 (CH),
126.08 (CH), 125.4 (CH), 123.9 (C), 120.6 (CH), 119.8 (CH), 118.1 (CN),
107.3 (CH), 50.1 (CH) ppm; HRMS (EI, m/z): [M]þ, Calcd for
Rf¼0.56 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n 3420,
2242 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
2.33 (s, 3H), 4.21 (d,
J¼8.82 Hz, 1H), 5.43 (d, J¼8.85 Hz, 1H), 6.01 (q, J¼1.07 Hz, 1H), 6.46
C18H14N2: 258.1157, found: 258.1158.
(d, J¼2.82 Hz, 1H), 6.79 (d, J¼8.43 Hz, 2H), 6.92 (m, 1H), 7.29 (m,
2H) ppm; 13C NMR (75.4 MHz, CDCl3):
d
154.0 (C), 144.2 (C), 144.0
4.2.15. 2-(N-Benzylamino)-2-phenylacetonitrile (Table 3, entry 5)
Rf¼0.62 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat): 3332,
(C), 129.5 (CHꢀ2), 120.4 (CH), 116.7 (CN), 114.4 (CHꢀ2), 110.4 (CH),
106.8 (CH), 44.3 (CH), 13.5 (CH3) ppm; HRMS (EI, m/z): [M]þ, Calcd
for C13H12N2O: 212.0950, found: 212.0948.
n
2228 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 1.83 (br s, 1H), 3.95 (q,
J¼14.85 Hz, 2H), 4.69 (s, 1H), 7.27–7.51 (m, 10H) ppm; 13C NMR
(75.4 MHz, CDCl3):
d
138.1 (C), 134.7 (C), 128.9 (CH), 128.8 (CHꢀ2),
4.2.9. 2-(N-Anilino)-2-(2-thienyl)acetonitrile (Table 2, entry 9)
128.5 (CHꢀ2), 128.3 (CHꢀ2), 127.5 (CH), 127.2 (CHꢀ2), 118.6 (CN),
Rf¼0.5 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n
3335,
53.3 (CH), 51.1 (CH2) ppm; HRMS (EI, m/z): [M]þ, Calcd for
2238 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
4.20 (d, J¼8.85 Hz, 1H),
C15H14N2: 222.1157, found: 222.1147.
5.58 (d, J¼9.24 Hz, 1H), 6.74 (d, J¼7.62 Hz, 2H), 6.89 (t, J¼7.43 Hz,
1H), 7.00 (q, J¼2.81 Hz, 1H), 7.21–7.33 (m, 4H) ppm; 13C NMR
4.2.16. 2-(N-Pyrrolidino)-2-phenylacetonitrile (Table 3, entry 6)
(75.4 MHz, CDCl3):
d
144.1 (C), 136.8 (C), 129.5 (CHꢀ2), 127.13 (CH),
Rf¼0.67 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n
127.07 (CH), 127.01 (CH), 120.6 (CH), 117.5 (CN), 114.5 (CHꢀ2), 46.1
(CH) ppm; HRMS (EI, m/z): [M]þ, Calcd for C12H10N2S: 214.0565,
found: 214.0561.
2226 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 1.82 (m, 4H), 2.64 (m, 4H),
5.04 (s, 1H), 7.34–7.53 (m, 5H) ppm; 13C NMR (75.4 MHz, CDCl3):
d
134.2 (C), 128.7 (CHꢀ3), 127.6 (CHꢀ2), 116.0 (CN), 59.2 (CH), 50.1
(CH2ꢀ2), 23.3 (CH2ꢀ2) ppm; HRMS (EI, m/z): [M]þ, Calcd for
4.2.10. 2-(N-Anilino)-2-(3-pyridyl)acetonitrile (Table 2, entry 10)
C12H14N2: 186.1157, found: 186.1149.
Rf¼0.24 (ethyl acetate/hexane¼1:2); FTIR (NaCl, neat):
n
3324,
2235 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
d
4.81 (d, J¼8.82 Hz, 1H),
4.2.17. 2-(N-Morpholino)-2-phenylacetonitrile (Table 3, entry 7)
5.46 (d, J¼8.82 Hz, 1H), 6.75 (d, J¼7.62 Hz, 2H), 6.88 (m, 1H), 7.21–
Rf¼0.43 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n
7.31 (m, 3H), 7.86 (m, 1H), 8.55 (d, J¼3.21 Hz, 1H), 8.71 (s, 1H) ppm;
2228 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
2.57 (t, J¼4.62 Hz, 4H),
13C NMR (75.4 MHz, CDCl3):
d
150.2 (CH), 148.2 (CH), 144.3 (C),
3.72 (t, J¼4.62 Hz, 4H), 4.81 (s, 1H), 7.37–7.54 (m, 5H) ppm; 13C
134.9 (CH), 130.0 (C), 129.4 (CHꢀ2), 123.8 (CH), 120.3 (CH), 117.3
NMR (75.4 MHz, CDCl3):
d
132.4 (C), 129.0 (CH), 128.7 (CHꢀ2), 127.9
(CN), 114.2 (CHꢀ2), 47.8 (CH) ppm; HRMS (EI, m/z): [M]þ, Calcd for
(CHꢀ2), 115.1 (CN), 66.5 (CH), 62.3 (CH2ꢀ2), 49.8 (CH2ꢀ2) ppm;
HRMS (EI, m/z): [M]þ, Calcd for C12H14N2O: 202.1106, found:
202.1099.
C
13H11N3: 209.0953, found: 209.0943.
4.2.11. 2-[N-(4-Chloroanilino)]-2-phenylacetonitrile
(Table 3, entry 1)
Acknowledgements
Rf¼0.5 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
n 3335,
2235 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
4.25 (d, J¼8.43 Hz, 1H),
We gratefully acknowledge the Nanyang Technological Univer-
sity, Ministry of Education (No. M45110000), and Biomedical
5.38 (d, J¼8.43 Hz, 1H), 6.69 (d, J¼8.43 Hz, 2H), 7.21 (d, J¼8.85 Hz,
2H), 7.44–7.58 (m, 5H) ppm; 13C NMR (75.4 MHz, CDCl3):
d
143.2
Research Council (A STAR grant M47110003) for the funding of this
*
(C), 133.4 (C), 129.5 (CH), 129.3 (CHꢀ2), 129.2 (CHꢀ2), 127.0 (CHꢀ2),
124.8 (C), 117.9 (CN), 115.3 (CHꢀ2), 50.0 (CH) ppm; HRMS (EI, m/z):
[M]þ, Calcd for C14H11ClN2: 242.0611, found: 242.0603.
research. We are also grateful to the National Natural Science
Foundation of China (No. 20472062 and 20672079) and Natural
Science Foundation of Jiangsu Province (No. BK2006048) for pro-
viding the research funding.
4.2.12. 2-[N-(4-Bromoanilino)]-2-phenylacetonitrile
(Table 3, entry 2)
References and notes
Rf¼0.5 (ethyl acetate/hexane¼1:4); FTIR (NaCl, neat):
2236 cmꢁ1 1H NMR (300 MHz, CDCl3):
4.17 (d, J¼8.04 Hz, 1H),
5.33 (d, J¼8.43 Hz, 1H), 6.60 (d, J¼8.82 Hz, 2H), 7.28–7.54 (m,
7H) ppm; 13C NMR (75.4 MHz, CDCl3):
143.6 (C), 133.4 (C), 132.2
n 3348,
;
d
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