Indium trichloride catalyzed one-step synthesis of α-amino nitriles by a three-component condensation of carbonyl compounds, amines and potassium cyanide

Article abstract of DOI:10.1016/S0040-4020(02)00132-1

A simple and general method has been developed for the synthesis of α-aminonitriles by a one-pot three-component condensation of aldehydes or ketones, amines and potassium cyanide in THF in presence of a catalytic amount of indium trichloride.

Full text of DOI:10.1016/S0040-4020(02)00132-1

TETRAHEDRON
Pergamon
Tetrahedron 58 ꢀ2002) 2529±2532
Indium trichloride catalyzed one-step synthesis of a-amino
nitriles by a three-component condensation of carbonyl
compounds, amines and potassium cyanide
p
Brindaban C. Ranu, Suvendu S. Dey and Alakananda Hajra
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 16 November 2001; accepted 7 February 2002
AbstractÐA simple and general method has been developed for the synthesis of a-aminonitriles by a one-pot three-component condensa-
tion of aldehydes or ketones, amines and potassium cyanide in THF in presence of a catalytic amount of indium trichloride. q 2002 Elsevier
Science Ltd. All rights reserved.
1. Introduction
The synthesis of a-amino nitriles has been the subject of
considerable current interest as these molecules serve as
useful intermediates towards preparation of a-amino
1
Scheme 1.
acids. The classical procedure, known as the Strecker
reaction for their synthesis involves the treatment of an
aldehyde or a ketone with alkaline cyanides and salts of
amines, and was discovered a century and a half ago. The
2. Results and discussion
2
reaction is usually carried out in aqueous solution and the
work-up pr ocedure is also tedious. Thus, several modi®ca-
tions of the Strecker reaction have been reported using a
In a typical general procedure, a mixture of a carbonyl
compound ꢀaldehyde or ketone), an amine and potassium
cyanide in THF was stirred ꢀfor aldehydes) or re¯uxed ꢀin
case of ketones) in presence of indiumꢀIII) chloride
ꢀ30 mol%) for a certain period of time ꢀTLC). Extraction
with ether and puri®cation by column chromatography over
silica gel furnished the pure product. A wide range of struc-
turally varied aldehydes and ketones were coupled with a
variety of aliphatic and aromatic amines and potassium
cyanide by this procedure through a single step operation
to produce the corresponding a-amino nitriles. The results
are summarized in Table 1. It was found that aldehydes, in
general, including aromatic, aliphatic and heterocyclic units
participate readily using this procedure, whereas only cyclic
ketones produced satisfactory results. Acyclic ketones
largely remained inert; longer reaction times and greater
amounts of indium trichloride also failed to make a signi®-
cant improvement. Conjugated aldehydes and ketones react
by this procedure to furnish mainly tarry material. On the
other hand, aliphatic and aromatic primary amines and
cyclic secondary amines like pyrrolidine and morpholine
are readily coupled. Although the amount of catalyst has
been optimized to 30 mol%, lesser amount ꢀ10±20 mol%)
also worked with longer reaction times. In general, the
reactions are considerably fast. No undesired side product
was isolated. The yields are reasonably good for a three-
component coupling reaction. Notably, this reaction has
3
variety of cyanide reagents, such as a-trimethylsiloxy-
3
b
3a
nitriles, diethyl phosphorocyanidate, under different
reaction conditions. However, many of these reagents are
not easily accessible due to their high cost and thus there is a
need for a more simple, straight-forward and cost-effective
method for the synthesis of these useful compounds.
Recently, indiumꢀIII) chloride has emerged as a powerful
Lewis acid catalyst in a variety of organic transformations.
4
5
Our own work also found InCl to be a very ef®cient
3
catalyst for two and three component condensation reaction
involving addition of a nucleophile to the imine generated in
situ from a carbonyl compound and an amine. This
prompted us to explore the addition of a cyanide ion to an
imine under indiumꢀIII) chloride catalysis and we have
discovered an excellent modi®cation of the Strecker
synthesis by a one-pot procedure ꢀScheme 1).
Keywords: a-amino nitriles; one-pot three-component condensation;
indium trichloride.
p
Corresponding author. Tel.: 191-033-4734971; fax: 191-033-4732805;
e-mail: ocbcr@mahendra.iacs.res.in
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020ꢀ02)00132-1

2530
B. C. Ranu et al. / Tetrahedron 58 )2002ꢀ 2529±2532
Table 1. Synthesis of a-amino nitriles
1
R
2
a
Entry
R
R
Time ꢀh)
Yield ꢀ%)
1
2
3
4
Ph
Ph
Ph
Ph
H
H
H
H
Ph
PhCH
3
CH ꢀCH
6
5
5
5
75
73
69
70
2
2 3
)
3 2
ꢀCH )
CH
5
Ph
H
4
74
6
7
8
9
1
1
Ph
Ph
Ph
m-ꢀOCH
m-ꢀOCH
m-ꢀOCH
H
H
H
H
H
H
o-ꢀCH
Pyrrolidine
Morpholine
3
)±C
6
H
4
5
4
4
5
5
5
82
89
82
75
87
93
3
3
3
)±C
)±C
)±C
6
H
6
H
6
H
4
4
4
3 2 3
CH ꢀCH )
Ph
0
1
PhCH
2
2
1
1
1
2
3
4
H
H
H
PhCH
8
8
5
62
47
84
PhCH
2
PhCH
2
2
15
16
17
18
19
20
21
22
ꢀCH
ꢀCH
3
CH ꢀCH
Cyclohexanone
Cyclohexanone
3-Methyl cyclohexanone
3-Methyl cyclohexanone
3-Methyl cyclohexanone
3
)
)
2
CH
CH
H
H
H
PhCH
5
5
5
14
14
14
4
80
78
60
66
64
66
70
70
3
2
Pyrrolidine
Pyrrolidine
2
)
2
PhCH
CH ꢀCH
PhCH
2
3
2 3
)
2
Pyrrolidine
Morpholine
4
a
Yields refer to those of pure isolated products fully characterised by spectral data.
been carried out under Lewis acid catalysis unlike many
conventional procedures using basic conditions.
The aldehydes, ketones, amines are all commercially avail-
able and were distilled before use. Potassium cyanide ꢀSD,
India) and indiumꢀIII) chloride ꢀAldrich) were used as such.
THF was distilled over potassium-benzophenone before
use.
2
,3
3. Conclusion
The present procedure using indium trichloride provides an
ef®cient synthesis of a-amino nitriles by a one-pot three
component coupling of carbonyl compound, amine and
cyanide. The signi®cant features of this methodology are:
4.1.1. General procedure for the synthesis of a-amino
nitriles. Representative procedure for the coupling of
benzyldehyde, benzyl amine and potassium cyanide
%entry 2, Table 1). A mixture of benzaldehyde ꢀ212 mg,
2 mmol), benzyl amine ꢀ235 mg, 2.2 mmol) and potassium
cyanide ꢀ198 mg, 3.0 mmol) in dry THF ꢀ6 mL) was stirred
in presence of indium trichloride ꢀ132 mg, 0.6 mmol,
ꢀ
a) operational simplicity; ꢀb) use of cheap commercially
available reagents ꢀc) general applicability to different
types of aldehydes and amines and ꢀd) high yields of
products. We believe, this procedure will make a practical
30 mol%) at room temperature ꢀ28±308C) under a CaCl
2
2
,3
alternative to the existing ones in the literature.
moisture guard tube for the time required to complete the
reaction ꢀTLC). THF was then distilled off under vacuum
and the residue was taken upin ether. The ether solution was
4. Experimental
washed with brine, dried ꢀNa SO ) and evaporated to leave
2 4
the crude product which was puri®ed by column chromato-
graphy over silica gel ꢀhexane±ether 92:8) to furnish pure
4
.1. General
product, 2-ꢀN-benzylamino)-2-phenylacetonitrile as 2
colourless oil ꢀ324 mg, 73%); IR ꢀneat) 3325, 2233 cm ;
a
1
Melting points were determined on a glass disk with an
electrical bath and are uncorrected. H NMR ꢀ300 MHz)
1
1
H NMR d 7.52±7.49 ꢀm, 2H), 7.41±7.26 ꢀm, 6H), 7.18 ꢀt,
Jˆ7.9 Hz, 1H), 6.78 ꢀd, Jˆ8.1 Hz, 1H), 4.71 ꢀs, 1H), 3.94
1
and C NMR ꢀ75 MHz) spectra were run in CDCl solu-
3
3
1
3
tions. IR spectra were taken as neat for liquid compounds
and as KBr plates for solids. Elemental analyses were done
by a Perkin±Elmer autoanalyzer. Column chromatography
was performed on silica gel ꢀ60±120 mesh, SRL, India).
ꢀAB q, Jˆ13.4 Hz, 2H); C NMR d 138.5, 135.1, 130.0
ꢀ2C), 129.5 ꢀ2C), 129.1 ꢀ2C), 128.9 ꢀ2C), 128.1 ꢀ2C), 119.1,
H N : C, 81.05; H, 6.35; N,
14 2
53.9, 51.7. Anal. Calcd for C15
12.60. Found: C, 80.86; H, 6.24; N, 12.34.

B. C. Ranu et al. / Tetrahedron 58 )2002ꢀ 2529±2532
2531
This procedure is followed for all the reactions enlisted in
Table 1. However, the reactions were carried out under
re¯ux in case of ketones. The products were identi®ed by
their IR, H and C NMR spectral data and elemental
analysis. These data are presented below in order of their
entries in Table 1.
4.1.9. 2-%N-n-Butylamino)-2-%3-methoxyphenyl)aceto-
nitrile %entry 9). Colourless oil ꢀ75%); IR ꢀneat) 3319,
2
1 1
2223 cm ; H NMR d 7.27 ꢀt, Jˆ9.8 Hz, 1H), 7.11±7.06
1
13
ꢀm, 2H), 6.89 ꢀdd, Jˆ2.5, 8.2 Hz, 1H), 4.74 ꢀs, 1H), 3.73 ꢀs,
1
3
3H), 2.82 ꢀm, 2H), 1.50 ꢀm, 4H), 0.92 ꢀt, Jˆ7.1 Hz, 3H); C
NMR d 161.1, 132.9, 130.4, 119.8, 119.4, 114.9, 113.2,
55.7, 54.9, 47.5, 32.1, 20.7, 14.3. Anal. Calcd for
C H N O: C, 71.53; H, 8.31; N, 12.83. Found: C, 71.32;
H, 8.27; N, 12.61.
.1.2. 2-%N-Anilino)-2-phenylacetonitrile3 %entry 1). Pale
yellow crystal ꢀ75%); mp84±85 8C; IR ꢀKBr) 3336,
a
4
1
3
18
2
21 1
237 cm ; H NMR d 7.49 ꢀm, 2H), 7.36 ꢀm, 3H), 7.23
2
ꢀ
t, Jˆ7.9 Hz, 2H), 6.84 ꢀt, Jˆ7.4 Hz, 1H), 6.69 ꢀd,
4.1.10. 2-%N-Anilino)-2-%3-methoxyphenyl)acetonitrile
%entry 10). Colourless crystal ꢀ87%); mp60±61 8C; IR
1
3
Jˆ7.9 Hz, 2H), 5.33 ꢀs, 1H), 4.07 ꢀbr s, 1H); C NMR d
2
1
1
1
1
45.3, 134.5, 130.1 ꢀ2C), 130.0, 129.8 ꢀ2C), 127.8 ꢀ2C),
20.7, 118.9, 114.7 ꢀ2C), 50.6.
ꢀKBr) 3355, 2223 cm ; H NMR d 7.29 ꢀt, Jˆ7.6 Hz,
1H), 7.23±7.09 ꢀm, 4H), 6.94±6.84 ꢀm, 2H), 6.73 ꢀd,
Jˆ7.6 Hz, 2H), 5.34 ꢀd, Jˆ8.4 Hz, 1H), 4.13 ꢀbroad d,
1
3
4.1.3. 2-%N-n-Butylamino)-2-phenylacetonitrile %entry 3).
Colourless oil ꢀ69%); IR ꢀneat) 3319, 2229 cm ; H NMR
d 7.72±7.68 ꢀm, 2H), 7.35 ꢀm, 3H), 4.75 ꢀs, 1H), 2.77 ꢀm,
2
1
3
8
Jˆ8.4 Hz, 1H), 3.77 ꢀs, 3H); C NMR d 160.7, 147.2,
135.9, 130.9, 130.0 ꢀ2C), 120.7, 119.8, 118.7, 115.6,
114.6 ꢀ2C), 113.2, 55.9, 50.5. Anal. Calcd for C H N O:
2
1 1
1
5
14
2
1
3
H), 1.49±1.26 ꢀm, 4H), 0.91 ꢀt, Jˆ7.2 Hz, 3H); C NMR d
35.5, 129.4, 129.3 ꢀ2C), 127.7 ꢀ2C), 119.3, 54.9, 47.5,
2.2, 20.7, 14.3. Anal. Calcd for C H N : C, 76.56; H,
C, 75.61; H, 5.92; N, 11.67. Found: C, 75.34; H, 5.90; N,
11.61.
1
2
16
2
.57; N, 14.88. Found: C, 76.39; H, 8.42; N, 14.75.
4.1.11. 2-%N-Benzylamino)-2-%3-methoxyphenyl)aceto-
nitrile %entry 11). Colourless oil ꢀ93%); IR ꢀneat) 3323,
2
1 1
4
Colourless oil ꢀ70%); IR ꢀneat) 3319, 2223 cm ;
.1.4. 2-%N-Isopropyl)-2-phenylacetonitrile %entry 4).
2
2223 cm ; H NMR d 7.38±7.26 ꢀm, 6H), 7.23 ꢀm, 2H),
6.86 ꢀdd, Jˆ2.5, 9.4 Hz, 1H), 4.66 ꢀs, 1H), 3.94 ꢀAB q,
1
1
H
NMR d 7.52±7.48 ꢀm, 2H), 7.43±7.34 ꢀm, 3H), 4.75 ꢀs,
1
3
Jˆ13.0 Hz, 2H), 3.77 ꢀs, 3H), 1.84 ꢀbraod s, 1H);
C
1
3
1
1
2
H), 3.21 ꢀm, 1H), 1.14 ꢀd, Jˆ6.2 Hz, 6H); C NMR d
35.9, 129.4 ꢀ2C), 129.3, 127.7 ꢀ2C), 119.4, 52.6, 47.6,
1.9, 20.7. Anal. Calcd for C H N : C, 75.82; H, 8.10;
NMR d 160.5, 138.6, 136.7, 130.4, 128.9 ꢀ2C), 129.8
ꢀ2C), 128.4, 119.9, 119.1, 114.9, 113.4, 55.7, 53.8, 51.6.
Anal. Calcd for C H N O: C, 76.16; H, 6.39; N, 11.10.
1
1
14
2
16 16
2
N, 16.08. Found: C, 75.56; H, 8.08; N, 15.82.
Found: C, 75.86; H, 6.32; N, 11.02.
4
5
2
3
.1.5. 2-%N-Cyclohexylamino)-2-phenylacetonitrile %entry
). Colourless crystal ꢀ74%); mp57±58 8C; IR ꢀKBr) 3311,
229 cm ; H NMR d 7.53±7.48 ꢀm, 2H), 7.41±7.32 ꢀm,
4.1.12. 2-%N-Benzylamino)-2-thiophenylacetonitrile %entry
12). Colourless oil ꢀ62%); IR ꢀneat) 3325, 2227 cm ; H
2
1 1
2
1 1
NMR d 7.41±7.22 ꢀm, 7H), 6.99±6.96 ꢀm, 1H), 4.93 ꢀs,
1H), 3.98 ꢀAB q, Jˆ13.0 Hz, 2H), 2.05 ꢀbroad s, 1H);
1
3
13
C
NMR d 138.7, 138.3, 129.1 ꢀ2C), 128.9, 128.8 ꢀ2C), 128.2,
H), 4.82 ꢀs, 1H), 2.86 ꢀm, 1H), 1.97±1.18 ꢀm, 10H);
C
NMR d 130.7, 129.4 ꢀ2C), 129.3, 127.7 ꢀ2C), 119.8, 55.3,
2.1, 34.3, 32.4, 26.4, 25.1, 24.7. Anal. Calcd for C H N :
C, 78.46; H, 8.47; N, 13.07. Found: C, 78.37; H, 8.33; N,
5
127.2, 126.8, 118.4, 51.3, 49.7. Anal. Calcd for C H N S:
13 12
1
4
18
2
2
C, 68.39; H, 5.30; N, 12.27. Found: C, 68.24; H, 5.19; N,
12.14.
1
2.86.
4
6
2
3
.1.6. 2-[N-%2-Methylanilino)]-2-phenylacetonitrile %entry
). Colourless crystal ꢀ82%); mp72±73 8C; IR ꢀKBr) 3361,
4.1.13. 2-%N-Benzylamino)-2-furfurylacetonitrile %entry
2
1 1
13). Colourless oil ꢀ47%); IR ꢀneat) 3325, 2227 cm ; H
NMR d 7.48±7.19 ꢀm, 7H), 6.30 ꢀm, 1H), 4.75 ꢀs, 1H), 3.95
2
1 1
235 cm ; H NMR d 7.70±7.67 ꢀm, 2H), 7.53±7.51 ꢀm,
H), 7.25 ꢀm, 2H), 6.89 ꢀt, Jˆ7.8 Hz, 2H), 5.50 ꢀd,
1
3
ꢀAB q, Jˆ12.9 Hz, 2H), 1.98 ꢀbraod s, 1H); C NMR d
147.8, 143.9, 138.1, 128.8 ꢀ2C), 128.6 ꢀ2C), 127.7, 127.5,
111.1, 109.5, 51.3, 47.6. Anal. Calcd for C H N O: C,
1
3
Jˆ8.3 Hz, 1H), 2.21 ꢀs, 3H); C NMR d 143.3, 134.7,
1
1
8
31.2, 130.0, 129.9 ꢀ2C), 127.8, 127.7 ꢀ2C), 124.1, 120.4,
18.9, 112.2, 50.5, 17.9. Anal. Calcd for C H N : C,
1.05; H, 6.35; N, 12.60. Found: C, 80.82; H, 6.11; N, 12.42.
1
3
12
2
73.57; H, 5.70; N, 13.20. Found: C, 73.38; H, 5.61; N, 13.14.
1
5
14
2
4.1.14. 2-%N-Benzylamino)-2-piperonylacetonitrile %entry
14). Colourless crystal ꢀ84%); mp62±63 8C; IR ꢀKBr) 3315,
4.1.7. 2-Phenyl-2-%N-pyrrolidino)acetonitrile %entry 7).
Colourless oil ꢀ89%); IR ꢀneat) 2223 cm ; H NMR d
2
1
1
21 1
2227 cm ; H NMR d 7.28 ꢀm, 6H), 6.99 ꢀs, 1H), 6.81 ꢀs,
1H), 5.97 ꢀm, 2H), 4.64 ꢀs, 1H), 3.97 ꢀAB q, Jˆ12.9 Hz,
7
2
1
.53±7.49 ꢀm, 2H), 7.43±7.31 ꢀm, 3H), 5.03 ꢀs, 1H),
.71±2.58 ꢀm, 4H), 1.89±1.75 ꢀm, 4H); C NMR d
34.7, 129.2 ꢀ2C), 129.1, 128.0 ꢀ2C), 116.5, 59.7, 50.7
1
3
13
2H), 1.79 ꢀbroad s, 1H); C NMR d 148.8, 138.7, 129.2
ꢀ2C), 129.1, 129.0, 128.9 ꢀ2C), 128.2, 121.4, 119.3, 108.9,
108.4, 102.0, 53.7, 51.7. Anal. Calcd for C H N O : C,
72.17; H, 5.30; N, 10.52. Found: C, 72.14; H, 5.30; N, 10.41.
ꢀ
2C), 23.9 ꢀ2C). Anal. Calcd for C H N : C, 77.38; H,
12 14 2
16 14
2
2
7
.58; N, 15.04. Found: C, 77.12; H, 7.42; N, 14.91.
4
.1.8. 2-%N-Morpholino)-2-phenylacetonitrile3a %entry 8).
Colourless crystal ꢀ82%); mp68±69 8C; IR ꢀKBr)
223 cm ; H NMR d 7.53±7.34 ꢀm, 5H), 4.81 ꢀt,
13
4.1.15. 2-%N-Benzylamino)-2-isopropylacetonitrile %entry
2
1 1
15). Colourless oil ꢀ80%); IR ꢀneat) 3347, 2223 cm ; H
NMR d 7.36±7.23 ꢀm, 5H), 4.06 ꢀd, Jˆ13.0 Hz, 1H), 3.79
ꢀd, Jˆ13.0 Hz, 1H), 3.25 ꢀd, Jˆ6.0 Hz, 1H), 1.98 ꢀm, 1H),
1.55 ꢀbroad s, 1H), 1.08 ꢀd, Jˆ6.8 Hz, 3H), 1.07 ꢀd,
2
1
1
2
Jˆ4.4 Hz, 4H), 2.57 ꢀt, Jˆ4.5 Hz, 4H); C NMR d 132.9,
29.9, 129.3 ꢀ2C), 128.4 ꢀ2C), 115.6, 62.1 ꢀ2C), 62.8, 50.4
2C).
1
ꢀ
1
3
Jˆ6.7 Hz, 3H); C NMR d 138.3, 128.5 ꢀ2C), 128.4

2532
B. C. Ranu et al. / Tetrahedron 58 )2002ꢀ 2529±2532
ꢀ2C), 127.4, 119.2, 56.2, 51.7, 31.5, 19.2, 18.2. Anal. Calcd
for C H N : C, 76.56; H, 8.57; N, 14.88. Found: C, 76.48;
H, 8.52; N, 14.71.
NMR d 2.79±2.66 ꢀm, 4H), 2.17±2.04 ꢀm, 2H), 1.82±1.57
13
ꢀm, 8H), 1.37±1.10 ꢀm, 3H), 0.96 ꢀd, Jˆ6.4 Hz, 3H);
NMR d 199.6, 63.3, 48.3 ꢀ2C), 44.5, 36.1, 33.7, 29.7, 23.6
2C), 23.3, 22.1. Anal. Calcd for C H N : C, 74.95; H,
C
1
2
16
2
ꢀ
1
2
20
2
4
1
.1.16. 2-Isopropyl-2-%N-pyrrolidino)acetonitrile %entry
6). Colourless oil ꢀ78%); IR ꢀneat) 2222 cm ; H NMR
10.48; N, 14.57. Found: C, 74.85; H, 10.42; N, 14.37.
2
1 1
d 3.29 ꢀd, Jˆ10.1 Hz, 1H), 2.61 ꢀm, 4H), 1.92 ꢀm, 1H), 1.82
4.1.22. 1-Cyano-1-%N-morpholino)-3-methylcyclohexane
%entry 22). Yellowish white crystal ꢀ70%); mp56±57 8C;
ꢀ
m, 4H), 1.12 ꢀd, Jˆ6.6 Hz, 3H), 1.02 ꢀd, Jˆ6.6 Hz, 3H);
1
3
21 1
C NMR d 117.8, 63.2, 50.5 ꢀ2C), 31.1, 23.9 ꢀ2C), 20.4,
9.7. Anal. Calcd for C H N : C, 71.01; H, 10.59; N, 18.40.
IR ꢀKBr) 2216 cm ; H NMR d 3.74 ꢀt, Jˆ4.6 Hz, 4H),
1
Found: C, 71.12; H, 10.35; N, 18.26.
2.69±2.62 ꢀm, 4H), 2.27±2.17 ꢀm, 2H), 1.87±1.59 ꢀm, 5H),
9
16
2
1
3
1.30±1.21 ꢀm, 2H), 0.97 ꢀd, Jˆ6.2 Hz, 3H); C NMR d
20.1, 68.2 ꢀ2C), 63.3, 48.5 ꢀ2C), 43.0, 34.7, 34.6, 30.7,
23.9, 23.3. Anal. Calcd for C12 O: C, 69.19; H, 9.68;
1
4
1
.1.17. 2-n-Propyl-2-%N-pyrrolidino)acetonitrile %entry
7). Colourless oil ꢀ60%); IR ꢀneat) 2221 cm ; H NMR
H N
20 2
2
1 1
N, 13.45. Found: C, 69.12; H, 9.59; N, 13.23.
d 3.74 ꢀt, Jˆ7.8 Hz, 1H), 2.67 ꢀm, 4H), 1.85±1.68 ꢀm, 6H),
1
3
1
.49 ꢀm, 2H), 0.97 ꢀt, Jˆ7.9 Hz, 3H); C NMR d 94.2, 53.1,
Acknowledgements
4
C H N : C, 71.01; H, 10.59; N, 18.4. Found: C, 71.08; H,
7.9 ꢀ2C), 32.7, 21.4 ꢀ2C), 17.36, 11.50. Anal. Calcd for
9
16
2
We are pleased to acknowledge the ®nancial support from
CSIR, New Delhi for this investigation. S. S. D and A. H.
are also thankful to CSIR for their fellowships.
1
0.38; N, 18.29.
4
1
.1.18. 1-%N-Benzylamino)-1-cyanocyclohexane %entry
8). Colourless oil ꢀ66%); IR ꢀneat) 3313, 2219 cm ; H
2
1 1
NMR d 7.40±7.30 ꢀm, 5H), 3.92 ꢀs, 2H), 2.07±1.54 ꢀm,
1
References
1
0H); C NMR d 139.8, 128.9 ꢀ2C), 128.8 ꢀ2C), 127.8,
3
122.6, 57.8, 49.0, 36.5 ꢀ2C), 25.57, 22.72 ꢀ2C). Anal.
Calcd for C H N : C, 78.46; H, 8.47; N, 13.07. Found:
C, 78.35; H, 8.42; N, 13.00.
1
. March, J. Advanced Organic Chemistry; 4th ed.; Wiley: New
York, 1999; p965.
1
4
18
2
2
. Strecker, A. Ann. Chem. Pharm. 1850, 75, 27.
. ꢀa) Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett.
3
4
1
.1.19. 1-%N-n-Butylamino)-1-cyanocyclohexane %entry
1979, 20, 4663. ꢀb) Mai, K.; Patil, G. Tetrahedron Lett. 1984,
25, 4583. ꢀc) Hanafusa, T.; Ichihara, J.; Ashida, T. Chem. Lett.
1987, 687. ꢀd) Iyer, M. S.; Gigstad, K. M.; Namdev, N. D.;
21 1
9). Colourless oil ꢀ64%); IR ꢀneat) 3315, 2218 cm ; H
NMR d 2.73 ꢀt, Jˆ6.6 Hz, 2H), 2.34 ꢀt, Jˆ6.4 Hz, 1H),
1
3
2
1
1
1
.04±1.24 ꢀm, 13H), 0.93 ꢀt, Jˆ6.9 Hz, 3H); C NMR d
22.7, 57.6, 43.9, 36.4 ꢀ2C), 32.6, 25.5, 22.6 ꢀ2C), 20.7,
4.2. Anal. Calcd for C H N : C, 73.28; H, 11.18, N,
Lipton, M. J. Am. Chem. Soc. 1996, 118, 4910. ꢀe) Sigman,
M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 5315.
1
1
20
2
ꢀ
f) Takamura, M.; Hamashima, Y.; Usuda, H.; Kanai, M.;
Shibasaki, M. Angew. Chem., Ind. Ed. Engl. 2000, 39, 1650.
g) Warmuth, R.; Munsch, T. E.; Stalker, R. A.; Li, B.; Beatty,
5.54. Found: C, 73.38; H, 11.01; N, 15.49.
ꢀ
4
%
.1.20. 1-%N-Benzylamino)-1-cyano-3-methylcyclohexane
entry 20). Colourless oil ꢀ66%); IR ꢀneat) 3313,
A. Tetrahedron 2001, 57, 6383.
. ꢀa) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149.
4
5
2
1
1
2223 cm ; H NMR d 7.39±7.28 ꢀm, 5H), 3.94 ꢀs, 2H),
13
2.09±1.11 ꢀm, 9H), 0.98 ꢀd, Jˆ6.4 Hz, 3H); C NMR d
139.8, 129.0 ꢀ2C), 128.9 ꢀ2C), 127.8, 122.5, 58.6, 49.0,
44.8, 36.4, 34.6, 29.8, 23.1, 22.4. Anal. Calcd for
ꢀ
b) Chauhan, K. K.; Frost, C. G. J. Chem. Soc., Perkin Trans.
2000, 3015. ꢀc) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347.
d) Ghosh, R. Indian J. Chem. 2001, 40B, 550.
. ꢀa) Ranu, B. C.; Hajra, A.; Jana, U. Org. Lett. 1999, 1, 1141.
b) Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2000, 41,
1
ꢀ
C H N : C, 78.90; H, 8.83; N, 12.27. Found: C, 78.79;
1
5
20
2
ꢀ
H, 8.81; N, 12.01.
531. ꢀc) Ranu, B. C.; Hajra, A.; Jana, U. J. Org. Chem. 2000, 65,
6270.
4
%
.1.21. 1-Cyano-1-%N-pyrrolidino)-3-methylcyclohexane
entry 21). Colourless oil ꢀ70%); IR ꢀneat) 2216 cm ; H
2
1 1