Synthesis of α-amino nitriles through Strecker reaction of aldimines and ketoimines by using nanocrystalline magnesium oxide

Article abstract of DOI:10.1016/j.tet.2008.01.128

Strecker reactions of various aldimines as well as ketoimines with TMSCN proceeded smoothly under mild conditions to give the corresponding α-amino nitriles and α,α-disubstituted α-amino nitriles, respectively, in good to excellent yields in the presence

Full text of DOI:10.1016/j.tet.2008.01.128

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Tetrahedron 64 (2008) 3351e3360
www.elsevier.com/locate/tet
Synthesis of a-amino nitriles through Strecker reaction of aldimines
and ketoimines by using nanocrystalline magnesium oxide
a
a
b
M. Lakshmi Kantam a, , Koosam Mahendar , Bojja Sreedhar , B.M. Choudary
*
a Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b Ogene Systems (I) Pvt. Ltd, Hyderabad 500 037, India
Received 22 October 2007; received in revised form 12 January 2008; accepted 31 January 2008
Available online 3 February 2008
Abstract
Strecker reactions of various aldimines as well as ketoimines with TMSCN proceeded smoothly under mild conditions to give the corre-
sponding a-amino nitriles and a,a-disubstituted a-amino nitriles, respectively, in good to excellent yields in the presence of nanocrystalline
magnesium oxide. The reaction proceeds through hypervalent silicate species by coordination to O2ꢀ/Oꢀ (Lewis basic site) of nanocrystalline
magnesium oxide, proved by 29Si NMR.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Strecker reaction; a-Amino nitriles; Aldimines; Ketoimines; Trimethylsilyl cyanide; Nanocrystalline magnesium oxide
1. Introduction
There have been numerous reports on sulfonyl and sulfinyl
imines in recent years, which are stable compounds.10 These
sulfonyl and sulfinyl groups are good activators of the C]N
bond for nucleophilic addition reactions. Therefore, the addi-
tion of trimethylsilyl cyanide (TMSCN) to these imines may
be a good method for obtaining a-amino nitriles. To our knowl-
edge, there are only few reports on Strecker reaction of sulfonyl
imines, using N-heterocyclic carbene (NHC),11a,b Feng’s
bifunctional N,N0-dioxide,11c Lewis acids and bases5d,6a as
catalysts to afford a-amino nitriles in good to excellent yields.
Recently, Toru et al. disclosed the Strecker reaction of sulfonyl
imines in the presence of chiral additives.12a,b Later Ooi et al.
reported Strecker reaction of N-arylsulfonyl imines and N-aryl-
sulfonyl a-amido sulfones under phase transfer conditions.12c,d
Some of the Strecker methodologies rely on the use of toxic
cyanide derivatives involving harsh reaction conditions, which
poses problems to be addressed, particularly when large-scale
applications are considered. In order to avoid partially this in-
convenience, acetone cyanohydrin, diethylaluminium cyanide,
TMSCN, etc. have been introduced as cyanide sources in the
Strecker reaction,12b,13 wherein TMSCN is a promising alter-
native, simplest, safe, easy to handle, most soluble and more
effective cyanide ion source for the nucleophilic addition
a-Amino nitriles are versatile precursors for the synthesis
of a-amino acids,1 various nitrogen and sulfur containing
heterocycles such as imidazoles, thiadiazoles2 and pharmaceu-
ticals.3 The Strecker reaction, nucleophilic addition of cyanide
ion to the imines, is of great importance to modern organic
chemistry as it offers one of the most direct and viable
methods for the synthesis of a-amino nitriles.4
The Strecker reaction has been studied extensively by using
various promising Lewis acid,5 Lewis base catalysts,6 metal
complexes and metalesalen complexes.7 In recent years, a num-
ber of highly effective catalysts have been successfully used for
asymmetric Strecker reactions, such as Lipton’s cyclic dipepti-
de,8a Corey’s cyclic guanidine,8b Jacobsen’s Schiff base8c,d and
Feng’s N,N0-dioxide.8e Strecker methodologies for the synthe-
sis of a-amino nitriles have been reported in ionic liquids and
water instead of regular organic solvents.9,5b
* Corresponding author. Tel./fax: þ91 40 27160921.
E-mail addresses: mlakshmi@iict.res.in, lkmannepalli@yahoo.com (M.L.
Kantam).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.128

3352
M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
reactions. Considering the importance of the Strecker reaction
for providing various chiral amino acid precursors in both
laboratory and industrial scale, it is highly desirable to develop
heterogeneous catalysts. However, there are only few reports
that are published on Strecker reaction by using heterogeneous
catalysts.14
Nanocrystalline metal oxides find excellent applications as
active adsorbents for gases, for destruction of hazardous chem-
icals15 and as catalysts for various organic transformations.16
These high reactivities are due to high surface areas combined
with unusually reactive morphologies. In continuation of our
work on nanomaterials, herein we report an effective Strecker
reaction of aldimines and ketoimines10 to afford a-amino
nitriles and a,a-disubstituted a-amino nitriles, respectively, in
high yields by using nanocrystalline magnesium oxide
(NAP-MgO) catalyst (Scheme 1).
DCM, DMF and THF. Among these, the rate of the reaction was
fast in THF and 97% yield of a-amino nitrile 2a obtained (Table
2, entry 5). Whereas the reaction between ketoimine 3a and
TMSCN in the presence of NAP-MgO in THF afforded the
product in moderate yields and the rate of the reaction was
slow (Table 2, entry 6). On switching THF to DMF, the reaction
was dramatically accelerated, affording quantitative yields of
the product (Table 2, entry 9). We observed, in the both cases,
with aldimine 1a and ketoimine 3a, the reactions in the non-
polar solvent, toluene took longer time. Notably, the reactions
of both aldimines and ketoimines when performed in dry
solvents under N2 atmosphere require long duration with slight
decrease in yields (Table 2, entries 10 and 11). This may indi-
cate that a trace amount of moisture was important to accelerate
the transformation of the substrates, which has been observed
earlier by Feng et al.11c When this transformation was carried
out on a large scale, there was a notable reduction in reaction
efficiency (Table 2, entry 12). It shows that adventitious mois-
ture may facilitate processes performed in smaller quantities.7a
PG
CN
R2
PG
R2
NAP - MgO
THF or DMF, rt
N
HN
R1
TMSCN
+
R1
R2 = H
2
R1= aliphatic, aromatic, heterocyclic, R2 = H 1
2 ≠ H
Ts
CN
R1, R2 = aliphatic, aromatic, heterocyclic
3
Ts
R
R
4
N
HN
NAP - MgO
solvent, rt
Scheme 1. NAP-MgO catalyzed Strecker reaction between aldimines or
ketoimines and TMSCN.
TMSCN
+
R
R = H
2a
R = H
1a
R = CH3 4a
R = CH3 3a
2. Results and discussion
Scheme 2. NAP-MgO catalyzed Strecker reaction between N-tosyl aldimine
1a or N-tosyl ketoimine 3a and TMSCN.
Various forms of magnesium oxide crystals CM-MgO (com-
mercial MgO, SSA: 30 m2/g), NA-MgO (NanoActive MgO,
conventionally prepared MgO, SSA: 250 m2/g), NAP-MgO
(NanoActive Plus MgO, aerogel prepared MgO, SSA:
590 m2/g) were initially evaluated in the Strecker reaction
between N-tosyl ketoimine 3a and TMSCN at room tempera-
ture in order to understand the relationship between structure
and reactivity. All these MgO crystals catalyze the Strecker
reaction in quantitative yields. However, the NAP-MgO was
found to be more active than NA-MgO and CM-MgO in the
Strecker reaction (Table 1).
Initially we studied the Strecker reaction with N-tosyl imines
1a or 3a as model substrates with TMSCN using NAP-MgO for
optimization (Scheme 2). The reaction was performed at room
temperature, between aldimine 1a and TMSCN in the presence
of NAP-MgO with different solvents like acetonitrile, toluene,
The substrate generality of the Strecker reaction was carried
out initially for N-sulfonyl aldimines with TMSCN (Scheme 3).
A variety of structurally different aldimines containing N-p-
toluene sulfonyl (Ts), N-benzene sulfonyl (Bzs), N-methane
sulfonyl (Ms), N-2,4,6-triisopropylbenzene sulfonyl (Tris) and
N-tert-butyl sulfonyl (Bus) imines were employed and the
results are summarized in Table 3. It was found that various
Table 2
Optimization of Strecker reaction of N-tosyl imines 1a or 3a with TMSCN
catalyzed by NAP-MgOa
Entry
Substrate
Solvent
Time
Yieldb (%)
1
1a
1a
1a
1a
1a
3a
3a
3a
3a
1ac
3ac
3ad
CH3CN
PhCH3
CH2Cl2
DMF
5 min
12 min
5 min
4 min
2 min
3 h
95
90
87
92
97
72
80
52
97
89
82
78
2
3
4
5
THF
THF
Table 1
Strecker reaction between N-tosyl ketoimine 3a and TMSCN with various
catalystsa
6
7
CH3CN
PhCH3
DMF
3 h
5 h
8
Entry
Catalyst
Time
Yieldb (%)
9
45 min
25 min
6 h
1
2
3
4
5
a
NAP-MgO
NA-MgO
CM-MgO
Sil-NAP-MgO
None
45 min, 1 hc
97, 95c
95
91
10
11
12
a
Dry THF
Dry DMF
DMF
3 h
6 h
3 h
8 h
8 h
89
18
Reaction conditions: N-tosyl imine 1a or 3a (1 mmol), TMSCN (1.2 mmol
for 1a, 1.5 mmol for 3a), catalyst (0.05 g), solvent (3 mL) at room
temperature.
Reaction conditions: N-tosyl ketoimine 3a (1 mmol), TMSCN (1.5 mmol),
b
catalyst (0.05 g), DMF (3 mL) at room temperature.
b
Isolated yield.
Under N2 atmosphere.
Reaction on 5 mmol scale.
c
Isolated yield.
Fourth cycle.
c
d

M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
Table 3 (continued)
3353
PG
PG
H
NAP - MgO
THF, rt
N
HN
R1
CN
TMSCN
+
Entry
R
PG
Ts
Time (min)
2
Yieldb (%)
R1
H
2a-w
1a-w
6
(1f)
90 (2f)
Scheme 3. NAP-MgO catalyzed Strecker reaction between various aldimines
and TMSCN.
H3CO
H3CO
8
7
(1g)
Ts
Ts
4
2
89 (2g)
91 (2h)
OCH3
aliphatic, aromatic and heterocyclic aldimines afforded good to
excellent yields. Various N-(arylmethylidene)-4-methyl benz-
enesulfonamides 1ae1h including a,b-unsaturated and hetero-
cyclic aldimines have showed high reactivity with excellent
yields. Moreover, other N-sulfonated imines such as N-benzene
sulfonated imines 1ke1m, N-mesylated imines 1ne1p and
N-tert-butyl sulfonated imine 1s also proceeded smoothly under
the optimized conditions and provided yields comparable with
those of 4-methyl benzenesulfonated imines. N-[(4-Methoxy-
phenyl)methylidene]-methanesulfonamide 1p took longer
reaction time (entry 16). Aliphatic aldimines 1i, 1j, 1s (entries
9, 10 and 19) furnished good yields. On the other hand, N-2,4,6-
triisopropylbenzene sulfonated aldimines 1q, 1r (entries 17 and
18) gave high yields, with low reactivity, which might be due to
the bulky and electron-donating groups on the aromatic ring.
Where N-tert-butyl carbonyl (Boc) aldimine 1t (entry 20) was
smoothly transformed to the corresponding a-amino nitrile in
good yields but unexpectedly, N-benzyl carbonyl (Cbz) aldi-
mine 1u (entry 21) was inactive and 94% of the starting material
Cbz imine 1u was recovered. In the Strecker reaction of N-
trimethylsilyl (N-TMS) aldimine 1v (entry 22), there was no
product formation, but imine was decomposed. N-p-Methoxy
phenyl (PMP) aldimine 1w (entry 23) afforded the product in
moderate yields on prolonged reaction time. Generally, the nor-
mal aldimines are less reactive than the activated N-sulfonyl
aldimines.
(1h)
Cl
NO2
CH3
9
(1i)
(1j)
Ts
Ts
2
2
89 (2i)
87 (2j)
10
11
12
(1k)
(1l)
Bzs
Bzs
2
2
93 (2k)
94 (2l)
H3C
13
(1m)
Bzs
2
91 (2m)
14
15
(1n)
(1o)
Ms
Ms
2
2
96 (2n)
92 (2o)
Cl
16
(1p)
Ms
10
97 (2p)
H3CO
Furthermore, many protocols are limited to aldimines only,
and are not applicable to ketoimines. In practice, the catalytic
Strecker reactions of ketoimines are not as easily performed as
those of aldimines. However, fewer systems have been devel-
oped for cyanation of ketoimines and the generation of a,a-
17
18
(1q)
(1r)
Tris
Tris
10
10
97 (2q)
95 (2r)
Cl
Table 3
Strecker reaction of various aldimines 1ae1w with TMSCN catalyzed by
NAP-MgOa
H3C
H3C
19
(1s)
Bus
2
91 (2s)
Entry
R
PG
Ts
Time (min)
2
Yieldb (%)
20
21
22
(1t)
(1u)
(1v)
Boc
Cbz
TMS
2
30
5
89 (2t)
N.Rc
1
(1a)
(1b)
97 (2a)
2
3
4
5
Ts
Ts
Ts
Ts
5
2
2
2
97 (2b)
92 (2c)
96 (2d)
H3CO
Cl
N.Dd
(1c)
(1d)
(1e)
23
(1w)
PMP
120
67 (2w)
Cl
a
Reaction conditions: aldimine 1aew (1 mmol), TMSCN (1.2 mmol),
catalyst (0.05 g), THF (3 mL) at room temperature.
O2N
b
Isolated yield.
No reaction.
Imine decomposed.
c
95 (2e)
O
d
(continued)

3354
M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
Table 4 (continued)
PG
PG
R2
NAP - MgO
DMF, rt
N
HN
R1
Entry
Ketoimine
Ts
Time (min)
90
Yieldb (%)
CN
R2
TMSCN
+
R1
N
4a-m
3a-m
5
(3e)
(3f)
(3g)
(3h)
(3i)
(3j)
(3k)
(3l)
97 (4e)
Scheme 4. NAP-MgO catalyzed Strecker reaction between various ketoimines
and TMSCN.
Ts
N
disubstituted a-amino nitriles. Jacobsen’s Schiff base
catalysts,17a,b Shibasaki’s Gd-complex catalysts,17c,d Vallee’s
metal complex catalysts17e,f and more recently Feng’s N,N0-
dioxide catalysts17g,11c have been developed for Strecker reac-
tion of ketoimines. These potential precursors to quaternary
a-amino acids display a wide assortment of interesting biolog-
ical properties and are important chiral building blocks for
pharmaceuticals.18 Herein, we report an effective Strecker
reaction of ketoimines by using nanocrystalline magnesium
oxide catalyst (NAP-MgO) (Scheme 4).
Substrate generality has been surveyed as shown in Table 4.
A variety of structurally different ketoimines containing N-p-
toluene sulfonyl (Ts), N-benzene sulfonyl (Bzs), N-methane
sulfonyl (Ms), N-tert-butyl sulfonyl (Bus) imines were
employed and the results are summarized in Table 4. The
Strecker reaction of aromatic ketoimines 3ae3k as well as
heterocyclic ketoimines 3l, 3m has been achieved with excel-
lent yields. Aliphatic ketoimine 3n (entry 14) showed high
reactivity in cyanation reaction under these optimized condi-
tions and high yields are obtained. Generally, aliphatic imines
are more reactive than aromatic imines because of resonance
stabilization in the latter. And a,b-unsaturated ketoimines
such as chalcone 3e and benzylidene acetone 3h furnished
high yields (entries 5 and 8), but the rate of the reaction is
slow, as compared to other aromatic ketoimines. Sterically
hindered ketoimines 3d, 3e, 3k, 3l (entries 4, 5, 11 and 12)
also furnished a,a-disubstituted a-amino nitriles with high
yields. Most of the products 2 and 4 in Tables 3 and 4 can
be directly subjected to acid hydrolysis to produce the corre-
sponding amino acids.
6
60
30
60
40
30
45
30
94 (4f)
96 (4g)
96 (4h)
95 (4i)
96 (4j)
91 (4k)
94 (4l)
Bzs
N
7
CH3
H3CO
Bzs
N
8
CH3
Ms
N
9
CH3
Bus
N
10
11
12
13
CH3
Bus
N
H3C
Bus
N
N
Bus
N
(3m)
(3n)
30
15
96 (4m)
91 (4n)
CH3
N
Bus
N
14
Table 4
Strecker reaction of various ketoimines 3ae3n with TMSCN catalyzed by
CH3
a
NAP-MgOa
Reaction conditions: ketoimine 3aen (1 mmol), TMSCN (1.5 mmol),
catalyst (0.05 g), DMF (3 mL) at room temperature.
Yieldb (%)
b
Entry
1
Ketoimine
Time (min)
45
Isolated yield.
Ts
N
As to the mechanism, we assumed that the cyanation of im-
ines with TMSCN proceeds through the formation of two ac-
tive intermediates either hypervalent silicate A or nucleophilic
cyanide ion B coordinated with the NAP-MgO as illustrated in
Scheme 5. There are extensive literature precedents that
TMSCN reacts rapidly with alcohols and phenols to produce
HCN and this has been demonstrated to be the actual cyanat-
ing agent in the Strecker reactions involving TMSCN.7aec,13d,e
In our present system, however, the substrates have proved to
be inert to HCN. The substrate 3a was treated with ethyl cya-
noformate followed by addition of acetic acid11c (see Section
4.5). This method is an alternative way instead of using
TMSCN and phenol that could produce HCN, which could
serve as a cyanating agent. The product 4a was not obtained
(3a)
(3b)
(3c)
(3d)
97 (4a)
CH3
Ts
N
2
3
4
60
55
45
97 (4b)
93 (4c)
CH3
H3CO
Cl
Ts
N
CH3
Ts
N
92 (4d)
(continued)

M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
3355
(CH3)3SiCN
PG
CH3
CH3
Si
CH3
CH3
CH3
NH
C
MgO
Si+
O-
Mg+
CN
O-
or
CH3
Mg+
R1
CN
2 or 4
CN-
R2
A
B
PG
H+
N
C
R1
R2
PG
CN
(CH3)Si
1 or 3
N
C
CH3
CH3
R1
CH3
CN
R2
Si+
CH3
CH3
Si
PG
PG
N-
C
O-
Mg+
N
C
O-
Mg+
CH3
R1
CN
R1
R2
R2
Mg2+
O2-
Mg2+
O2-
Mg2+
OH
MgO
=
HO
O2-
Mg2+
O2-
Scheme 5. Plausible mechanism for the Strecker reaction using NAP-MgO.
in the present system and also the evolved gas fragment m/z¼26,
due to CNꢀ ion was not observed in TGAeDTAeMS of
TMSCN treated NAP-MgO. So we assumed that intermediate
B may not be the active intermediate in the present system.
Therefore, we assumed that the reaction proceeds through the
possible active intermediate hypervalent silicate A in the present
system as showed in Scheme 5.11a,c,19
Trimethylsilyl cyanide was activated by O2ꢀ/Oꢀ (Lewis
base) of NAP-MgO catalyst, which forms a hypervalent silicate
A, coordinates with O2ꢀ/Oꢀ of the NAP-MgO, resulting in the
cyanide group being polarized to acquire more reactivity; mean-
while, imine 1 or 3 was activated by Mg2þ/Mgþ (Lewis acid) of
NAP-MgO. The highly reactive cyanide ion attacks the imine,
resulting in the formation of a nitrogen anion intermediate,
which coordinates with Mg2þ/Mgþ (Lewis acid) of NAP-MgO.
Thereafter the N-TMS intermediate was formed and hydrolyzed
to Strecker product 2 or 4 due to the cleavage of the rather labile
NeSi bond by a trace amount of moisture present in the solvent,
which is important to accelerate the transformation of the
substrates, as observed earlier by Feng et al.11c
in CDCl3, as detailed in Section 4. The 29Si NMR spectra were
recorded using tetramethyl silane as an internal standard. As
illustrated in Table 5, entry 1, TMSCN affords a signal at
d¼ꢀ11.45 ppm {lit.:19 d¼ꢀ11.5 ppm}. When TMSCN is
added to the solution of NAP-MgO, another signal was found
at d¼7.07 ppm {lit.:19 d¼7.1 ppm} (Table 5, entry 2). When
imine was added to the solution of NAP-MgO and TMSCN,
an identical spectrum was observed as to NAP-MgO (Table
5, entry 3). The spectral changes strongly indicate that the
environments around the silicon atoms of some TMSCN
species are changed when NAP-MgO is present. It is possible
that these silicon atoms of TMSCN could form five- or six-
coordinated hypervalent silicate species by coordination with
Table 5
29Si NMR chemical shifts of several systemsa
Entry
Components
d (ppm)
1
2
3
4
a
TMSCN
ꢀ11.45
TMSCNþNAP-MgO
TMSCNþNAP-MgOþimine
TMSCNþSil-NAP-MgO
7.07, ꢀ11.45
7.06, ꢀ11.45
7.05, ꢀ11.43
In order to confirm the hypothesis of hypervalent silicate
intermediate A, 29Si NMR (400 MHz) analyses were carried
out at 25 ꢁC in CDCl3.19 All the experiments were performed
Reaction conditions: ketoimine 3a (0.1 mmol), TMSCN (0.15 mmol),
catalyst (0.005 g), CDCl3 (0.5 mL) at 25 ꢁC.

3356
M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
O2ꢀ/Oꢀ (Lewis basic site) of NAP-MgO, but not the Bronsted
basic site (Scheme 5).20 This is proved, when TMSCN is
added to the solution of Sil-NAP-MgO, an almost identical
spectrum was observed as to NAP-MgO (Table 5, entry 4).
To understand the relationship between structure and reactiv-
ity of the catalyst in the Strecker reaction, it is important to know
the structure and nature of the reactive sites of NAP-MgO.
NAP-MgO has single-crystallite, three-dimensional polyhedral
structure, which possesses high surface concentrations of edge/
corner and various exposed crystal planes (such as 002, 001,
111), leading to inherently high surface reactivity per unit
area. Thus, NAP-MgO indeed displayed the highest activity
compared to that of NA-MgO and CM-MgO. Besides this, the
NAP-MgO has Lewis acid sites Mg2þ, Lewis basic sites O2ꢀ
and Oꢀ, lattice-bound and isolated Bronsted hydroxyls and
anionic and cationic vacancies.20 Strecker reactions are known
to be driven by base catalysts,6 and accordingly, the surface
eOH, O2ꢀ sites of these oxide crystals are expected to trigger
these reactions. To examine the role of eOH, the Sil-
NAP-MgO20e devoid of free eOH, were tested in Strecker reac-
tions. It is found that the rate of the reaction was slow, and longer
reaction time was required in Strecker reaction (Table 1, entry
4). Although both NAP-MgO and NA-MgO possess defined
shapes and the same average concentrations of surface eOH
groups, a possible rationale for the display of higher reactivity
to a-amino nitriles by the NAP-MgO is that the presence of
more surface Lewis acid sites Mg2þ ions (20%) and eOH
groups present on the edge and corner sites on the NAP-MgO,
which are stretched in three-dimensional space, are more iso-
lated and accessible for the reactants. Thus, NAP-MgO indeed
displayed the highest activity compared to NA-MgO and
CM-MgO. In the Strecker reaction, O2ꢀ/Oꢀ (Lewis base) of
NAP-MgO activates the trimethylsilyl cyanide, which forms
a hypervalent silicate, coordinates with O2ꢀ/Oꢀ of the
NAP-MgO. The Strecker reaction proceeds via dual activation
of both substrates (electrophiles and nucleophiles) by
NAP-MgO. Thus, the Lewis base moiety (O2ꢀ/Oꢀ) of the
catalyst activates the TMSCN and the Lewis acid moiety
(Mg2þ/Mgþ) activates the nitrogen of aldimines or ketoimines
(Scheme 5).13e,21
4. Experimental section
4.1. General remarks
Nanocrystalline MgO samples were obtained from Nano-
Scale Materials Inc., Manhattan, Kansas, USA. All catalysts
are calcined at 400 ꢁC for 4 h before use. All chemicals were
purchased from Aldrich Chemicals and S.D Fine Chemicals,
Pvt. Ltd., India and used as received. All solvents were used
LR grade and used as received from S.D Fine Chemicals Pvt.
Ltd., India. ACME silica gel (100e200 mesh) was used for
column chromatography and thin layer chromatography was
performed on Merck precoated silica gel 60-F254 plates. Melting
points were measured in open capillary tubes and are uncor-
rected. The IR spectra of all compounds were recorded on a
PerkineElmer, SpectrumGX FTIR spectrometer using KBr
pellet method. The IR values are reported in reciprocal centi-
1
metres (cmꢀ1). The H and 13C NMR spectra were recorded
on a Varian-Gemini 200 MHz and Bruker-Avance 300 MHz
Spectrometer. The 29Si NMR spectra were recorded on a
Varian-Unity 400 MHz Spectrometer. Chemical shifts (d) are
reported in parts per million, using TMS (d¼0) as an internal
standard in CDCl3. All the mass spectra were recorded on
QSTAR XL high resolution mass spectrometer (Applied Bio-
systems, Foster city, USA). Substrate imines 1aes,10 1tev,22
3aen10 were prepared according to reported literature methods.
4.2. Preparation of the different types of nanocrystalline MgO
catalysts20cee
Preparation of NA-MgO:20c,d Several grams of commer-
cially available MgO was boiled in 500 mL of distilled water
overnight (with magnetic stirring in a 1 L flask equipped with
a reflux condenser). After cooling, the slurry was filtered and
the filter cake was dried in an oven at 120 ꢁC. The dried pow-
der was broken into pieces and heat treated to 500 ꢁC under
vacuum in a Pyrex reaction tube that fit into a cylindrical
furnace. Heating took about 12 h, and the sample was main-
tained at 500 ꢁC for several hours, usually overnight. The
vacuum reached about 1ꢂ10ꢀ3 Torr.
The NAP-MgO was reused for four cycles with consistent
activity (Table 1, entry 1). After completion of the reaction,
catalyst was centrifuged and washed properly for several
times. The recovered catalyst was activated at 250 ꢁC for 1 h
under nitrogen atmosphere, before reuse.
Preparation of NAP-MgO:20c,d In a three-necked 2 L round
bottom flask equipped with a mechanical stirrer, water cooled
condenser, and argoninlet with a three-way stopcock was placed
300 mL of toluene. In another flask, 2.4 g (0.1 mol) of Mg turn-
ings was allowed to react with 100 mL of CH3OH under argon.
The resultant 1 M solution of Mg(OCH3)2 was added dropwise
to the toluene with vigorous stirring under argon. Then 4 mL
(0.22 mol) of distilled water was added dropwise from a syringe
over a 30 min period. This solution was stirred at room temper-
ature under argon overnight. The resultant slightly milky
solution (gel-like) was placed in an autoclave, slowly heated
to 265 ꢁC, vented, and thus converted to a Mg(OH)2 aerogel.20c
After cooling, the slurry was filtered, and the filter cake was
dried in an oven at 120 ꢁC. The dried powder was broken into
pieces and heat treated to 500 ꢁC under vacuum in a Pyrex reac-
tion tube that fit into a cylindrical furnace. Heating took about
3. Conclusion
In conclusion, nanocrystalline MgO has been demonstrated
to be an effective catalyst for the cyanation of aldimines as
well as ketoimines to afford a-amino nitriles and a,a-disubsti-
tuted a-amino nitriles, respectively, in high yields. To conclude,
the simplicity of our procedure, the mildness of the reaction
conditions, high yields, together with the ability to easy separa-
tion of reaction mixture, especially the reusability of the catalyst
demonstrates our method to be practical for the synthesis of
a-amino nitriles.

M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
3357
12 h, and the sample was maintained at 500 ꢁC for several hours,
usually overnight. The vacuum reached about 1ꢂ10ꢀ3 Torr.
Preparation of Sil-NAP-MgO:20e A mixture of 0.5 g of
NAP-MgO and 0.3 g of methoxytrimethyl silane in 20 mL of
toluene was refluxed for 7 h and the reaction mixture was al-
lowed to cool and centrifuged to obtain silylated NAP-MgO,
which was washed several times with n-pentane.
(ESI): m/z 354 (MþNaþ). HRMS (ESI): Anal. Calcd for
C15H13N3O4NaS: 354.0524. Found: 354.0529.
4.3.4. N-[Cyano-(2-furyl)methyl]-4-methylbenzene-
sulfonamide (2e)
Rf 0.6 (hexane/EtOAc 5:5), colourless solid; mp 98e
1
100 ꢁC. IR (KBr): 3260, 2243, 1341, 1162, 1090 cmꢀ1. H
NMR (CDCl3, 300 MHz): d¼2.47 (s, 3H), 5.3 (d, J¼9.2 Hz,
1H), 5.5 (d, J¼9.2 Hz, 1H), 6.35 (dd, J¼3.4, 1.6 Hz, 1H),
6.48 (d, J¼3.4 Hz, 1H), 7.34 (d, J¼8.3 Hz, 2H), 7.4 (d,
J¼1.6 Hz, 1H), 7.77 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3,
75 MHz): d¼21.5, 42.2, 110.3, 110.9, 114.6, 127.2, 129.9,
135.9, 144.0, 144.3, 144.6. Mass (ESI): m/z 299 (MþNaþ).
HRMS (ESI): Anal. Calcd for C13H12N2O3NaS: 299.0466.
Found: 299.0474.
4.3. Typical procedure for the Strecker reaction of aldimines
To a stirred solution of NAP-MgO (0.05 g) in THF (4 mL),
TMSCN (1.2 mmol) was added in one portion at ambient
temperature. After 5 min, aldimine 1 (1 mmol) was added to
the reaction mixture and stirred at room temperature. After com-
pletion of the reaction (as monitored by TLC), the catalyst was
centrifuged, and washed with ethyl acetate (3ꢂ5 mL). The com-
bined organic solvent was removed under reduced pressure, and
the crude product was purified by column chromatography on
silica gel (100e200 mesh) using ethyl acetate/hexane invarying
proportions as an eluent to afford the pure product 2. The phys-
ical data of the known products 2c, 2e, 2g, 2h, 2q, 2t and 2w were
comparable to the literature data.5a,11a The physical data of the
new products are given below.
4.3.5. N-[(E)-1-Cyano-3-phenyl-2-propenyl]-4-methyl-
benzenesulfonamide (2f)
Rf 0.46 (hexane/EtOAc 6:4), colourless solid; mp 99e
1
101 ꢁC. IR (KBr): 3236, 2228, 1353, 1162, 1638 cmꢀ1. H
NMR (CDCl3, 300 MHz): d¼2.47 (s, 3H), 3.65 (dd, J¼7.9,
6.1 Hz, 1H), 5.06 (d, J¼7.9 Hz, 1H), 6.06 (dd, J¼6.1,
16 Hz, 1H), 6.86 (d, J¼16 Hz, 1H), 7.06e7.11 (d, J¼8.3 Hz,
2H), 7.28e7.33 (m, 5H), 7.35 (d, J¼8.3 Hz, 2H). 13C NMR
(CDCl3, 75 MHz): d¼21.5, 35.8, 113.6, 126.2, 126.9, 127.5,
128.2, 128.3, 128.7, 129.9, 130.0, 143.3, 146.1. Mass (ESI):
m/z 335 (MþNaþ). HRMS (ESI): Anal. Calcd for
C17H16N2O2NaS: 335.0830. Found: 335.0842.
4.3.1. N-(Cyanophenylmethyl)-4-methylbenzenesulfon-
amide (2a)
Rf 0.52 (hexane/EtOAc 6:4), colourless solid; mp 152e
1
154 ꢁC. IR (KBr): 3255, 2228, 1334, 1156 cmꢀ1. H NMR
(CDCl3, 300 MHz): d¼2.48 (s, 3H), 5.02 (d, J¼9.4 Hz, 1H),
5.47 (d, J¼9.4 Hz, 1H), 7.37 (d, J¼8.3 Hz, 2H), 7.39e7.5 (m,
5H), 7.81 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3, 50 MHz):
21.7, 48.2, 116.2, 127.0, 127.2, 129.3, 129.8, 129.9, 131.9,
135.8, 144.6. Mass (ESI): m/z 309 (MþNaþ). HRMS (ESI):
Anal. Calcd for C15H14N2O2NaS: 309.0673. Found: 309.0682.
4.3.6. N-[Cyano-(2,4,5-trimethoxyphenyl)methyl]-4-methyl-
benzenesulfonamide (2g)
Rf 0.52 (hexane/EtOAc 6:4), colourless solid; mp 174e
175 ꢁC. IR (KBr): 3264, 2244, 1341, 1165, 1075,
1096 cmꢀ1
.
1H NMR (CDCl3, 200 MHz): d¼2.45 (s, 3H),
3.81 (s, 3H), 3.86 (s, 6H), 5.29 (d, J¼9.2 Hz, 1H), 5.43 (d,
J¼9.2 Hz, 1H), 6.45 (s, 1H), 6.7 (s, 1H), 7.3 (d, J¼8.1 Hz,
2H), 7.73 (d, J¼8.1 Hz, 2H). 13C NMR (CDCl3, 75 MHz):
d¼21.5, 44.8, 56.1, 56.3, 56.5, 97.2, 111.6, 112.3, 116.8,
127.1, 129.7, 136.4, 143.0, 144.1, 151.2. Mass (ESI): m/z 399
(MþNaþ). HRMS (ESI): Anal. Calcd for C18H20N2O5NaS:
399.0990. Found: 399.0996.
4.3.2. N-[Cyano-(4-methoxyphenyl)methyl]-4-methylbenzene-
sulfonamide (2b)
Rf 0.62 (hexane/EtOAc 5:5), colourless solid; mp 128e
1
129 ꢁC. IR (KBr): 3268, 2244, 1348, 1158, 1093 cmꢀ1. H
NMR (CDCl3, 300 MHz): d¼2.48 (s, 3H), 3.81 (s, 3H), 5.02
(d, J¼8.7 Hz, 1H), 5.39 (d, J¼8.7 Hz, 1H), 6.88 (d, J¼8.3 Hz,
2H), 7.35 (d, J¼8.7 Hz, 2H), 7.37 (d, J¼8.7 Hz, 2H), 7.79 (d,
J¼8.3 Hz, 2H). 13C NMR (CDCl3, 75 MHz): 21.4, 47.6, 55.4,
114.4, 116.5, 124.1, 127.1, 128.5, 129.8, 136.1, 144.4, 160.5.
Mass (ESI): m/z 339 (MþNaþ). HRMS (ESI): Anal. Calcd for
C16H16N2O3NaS: 339.0779. Found: 339.0785.
4.3.7. N-[Cyano-(4-chloro-3-nitrophenyl)methyl]-4-methyl-
benzenesulfonamide (2h)
Rf 0.34 (hexane/EtOAc 6:4), yellow solid; mp 125e127 ꢁC.
IR (KBr): 3315, 2323, 1334, 1157, 1540 cmꢀ1 1H NMR
.
(CDCl3, 300 MHz): d¼2.5 (s, 3H), 5.44 (d, J¼9.4 Hz, 1H),
5.5 (d, J¼9.4 Hz, 1H), 7.37 (d, J¼8.3 Hz, 2H), 7.62e7.69
(m, 2H), 7.76 (d, J¼8.3 Hz, 2H), 7.86 (s, 1H). 13C NMR
(CDCl3, 75 MHz): d¼21.6, 46.9, 115.1, 124.3, 127.1, 128.6,
130.2, 131.6, 132.5, 132.9, 135.4, 145.3, 147.9. Mass (ESI):
m/z 388 (MþNaþ). HRMS (ESI): Anal. Calcd for
C15H12N3O4NaSCl: 388.0134. Found: 388.0121.
4.3.3. N-[Cyano-(4-nitrophenyl)methyl]-4-methylbenzene-
sulfonamide (2d)
Rf 0.52 (hexane/EtOAc 6:4), orange solid; mp 120e122 ꢁC.
IR (KBr): 3279, 2238, 1338, 1159, 1523 cmꢀ1 1H NMR
.
(CDCl3, 300 MHz): d¼2.5 (s, 3H), 5.36 (d, J¼9.8 Hz, 1H),
5.56 (d, J¼9.8 Hz, 1H), 7.38 (d, J¼8.3 Hz, 2H), 7.71 (d,
J¼8.3 Hz, 2H), 7.79 (d, J¼9.1 Hz, 2H), 8.28 (d, J¼9.1 Hz,
2H). 13C NMR (CDCl3, 75 MHz): d¼21.6, 47.5, 115.4,
124.3, 127.2, 128.2, 130.2, 135.5, 138.7, 145.2, 148.5. Mass
4.3.8. N-(Cyanophenylmethyl)benzenesulfonamide (2k)
Rf 0.49 (hexane/EtOAc 6:4), light yellow solid; mp
.
100e102 ꢁC. IR (KBr): 3284, 2244, 1330, 1164 cmꢀ1 1H

3358
M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
NMR (CDCl3, 300 MHz): d¼5.13 (d, J¼9.1 Hz, 1H), 5.48 (d,
J¼9.1 Hz, 1H), 7.39e7.49 (m, 5H), 7.54e7.68 (m, 3H), 7.92
(d, J¼7.6 Hz, 2H). 13C NMR (CDCl3, 75 MHz): d¼48.2,
116.2, 127.0, 127.2, 129.3, 129.4, 129.9, 132.0, 133.6,
138.9. Mass (ESI): m/z 295 (MþNaþ). HRMS (ESI): Anal.
Calcd for C14H12N2O2NaS: 295.0517. Found: 295.0516.
d¼41.9, 48.0, 55.4, 114.9, 116.5, 126.8, 128.7, 161.3. Mass
(ESI): m/z 263 (MþNaþ). HRMS (ESI): Anal. Calcd for
C10H12N2O3NaS: 263.0466. Found: 263.0473.
4.3.14. N-[(4-Chlorophenyl)cyanomethyl]-2,4,6-triiso-
propylbenzenesulfonamide (2r)
Rf 0.49 (hexane/EtOAc 8:2), colourless solid; mp
4.3.9. N-[Cyano-(4-methylphenyl)methyl]benzenesulfon-
amide (2l)
Rf 0.36 (hexane/EtOAc 6:4), colourless solid; mp
112e113 ꢁC. IR (KBr): 3280, 2234, 1335, 1164 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz): d¼2.36 (s, 3H), 5.2 (d, J¼9.1 Hz,
1H), 5.42 (d, J¼9.1 Hz, 1H), 7.17 (d, J¼8.1 Hz, 2H), 7.32
(d, J¼8.1 Hz, 2H), 7.53e7.67 (m, 3H), 7.89e7.93 (m, 2H).
13C NMR (CDCl3, 75 MHz): d¼21.1, 47.9, 116.4, 126.9,
127.2, 129.0, 129.3, 129.9, 133.5, 138.9, 139.9. Mass (ESI):
m/z 309 (MþNaþ). HRMS (ESI): Anal. Calcd for
C15H14N2O2NaS: 309.0673. Found: 309.0679.
117e118 ꢁC. IR (KBr): 3371, 2238, 1322, 1148 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz): d¼1.28 (d, J¼5.3 Hz, 6H), 1.31
(d, J¼5.3 Hz, 12H), 2.92 (septet, J¼6.8 Hz, 1H), 4.03 (septet,
J¼6.8 Hz, 2H), 4.98 (d, J¼8.6 Hz, 1H), 5.47 (d, J¼8.6 Hz,
1H), 7.18 (s, 2H), 7.37 (d, J¼8.7 Hz, 2H), 7.43 (d,
J¼8.7 Hz, 2H). 13C NMR (CDCl3, 75 MHz): d¼23.5, 24.7,
24.8, 29.9, 34.2, 47.9, 116.4, 124.1, 128.6, 129.5, 131.7,
150.4, 153.8. Mass (ESI): m/z 455 (MþNaþ). HRMS (ESI):
Anal. Calcd for C23H29N2O2NaSCl: 455.1535. Found:
455.1539.
4.3.15. N-[1-Cyano-(3-methyl)butyl]-2-methyl-2-propane-
sulfonamide (2s)
4.3.10. N-[Cyano-(2-napthyl)methyl]benzenesulfon-
amide (2m)
Rf 0.5 (hexane/EtOAc 6:4), colourless solid; mp
164e166 ꢁC. IR (KBr): 3275, 2250, 1331, 1156 cmꢀ1
NMR (CDCl3, 200 MHz): d¼5.08 (d, J¼8.8 Hz, 1H), 5.66
(d, J¼8.8 Hz, 1H), 7.49e7.68 (m, 5H), 7.82e7.98 (m, 7H).
13C NMR (CDCl3, 50 MHz): d¼48.5, 116.2, 123.9, 126.6,
127.2, 127.3, 127.5, 127.8, 128.2, 129.5, 129.7, 132.8,
133.7, 139.1. Mass (ESI): m/z 345 (MþNaþ). HRMS (ESI):
Anal. Calcd for C18H14N2O2NaS: 345.0673. Found: 345.0683.
Rf 0.52 (hexane/EtOAc 6:4), white solid; mp 102e103 ꢁC.
1
IR (KBr): 3275, 2238, 1331, 1145 cmꢀ1. H NMR (CDCl3,
.
1H
300 MHz): d¼1.01 (d, J¼3.1 Hz, 3H), 1.03 (d, J¼3.1 Hz,
3H), 1.44 (s, 9H), 1.72e1.78 (m, 2H), 1.83e1.97 (m, 1H),
4.35 (q, 1H), 4.65 (d, J¼9.1 Hz, 1H). 13C NMR (CDCl3,
75 MHz): d¼21.7, 21.9, 24.0, 24.5, 43.7, 44.2, 60.4, 119.0.
Mass (ESI): m/z 255 (MþNaþ). HRMS (ESI): Anal. Calcd
for C10H20N2O2NaS: 255.1143. Found: 255.1149.
4.4. Typical procedure for the Strecker reaction of ketoimines
4.3.11. N-(Cyanophenylmethyl)methanesulfonamide (2n)
Rf 0.55 (hexane/EtOAc 5:5), white solid; mp 104e106 ꢁC.
To a stirred solution of NAP-MgO (0.05 g) in DMF (4 mL),
TMSCN (1.5 mmol) was added in one portion at ambient
temperature. After 5 min, ketoimine 3 (1 mmol) was added to
the reaction mixture and stirred at room temperature. After com-
pletion of the reaction (as monitored by TLC), the catalyst was
centrifuged, and washed with ethyl acetate (3ꢂ5 mL), water
(2ꢂ5 mL) was added to the filtrate, and then the reaction mix-
ture was extracted with ethyl acetate (2ꢂ5 mL). The combined
organic layers werewashed with brine (2ꢂ5 mL), and dried over
anhydrous Na2SO4. The protocol involving addition of water
followed by extraction with ethyl acetate is required to remove
DMF from reaction mixture. The solvent was removed under re-
duced pressure, and the crude product was purified by column
chromatography on silica gel (100e200 mesh) using ethyl
acetate/hexane in varying proportions as an eluent to afford
the pure product 4. The physical data of the known products
4ae4f were comparable to the literature data.11b,c The physical
data of the new products are given below.
1
IR (KBr): 3252, 2244, 1324, 1161 cmꢀ1. H NMR (CDCl3,
300 MHz): d¼3.13 (s, 3H), 5.02 (d, J¼8.3 Hz, 1H), 5.56 (d,
J¼8.3 Hz, 1H), 7.43e7.48 (m, 3H), 7.52e7.56 (m, 2H). 13C
NMR (CDCl3, 75 MHz): d¼41.8, 48.3, 117.0, 127.2, 129.5,
130.1, 131.8. Mass (ESI): m/z 233 (MþNaþ). HRMS (ESI):
Anal. Calcd for C9H10N2O2NaS: 233.0360. Found: 233.0368.
4.3.12. N-[(4-Chlorophenyl)cyanomethyl]methanesulfon-
amide (2o)
Rf 0.52 (hexane/EtOAc 6:4), colourless solid; mp
154e155 ꢁC. IR (KBr): 3217, 2250, 1324, 1157 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz): d¼3.16 (s, 3H), 4.89 (br s, 1H),
5.56 (br s, 1H), 7.45 (d, J¼8.7 Hz, 2H), 7.52 (d, J¼8.7 Hz,
2H). 13C NMR (CDCl3, 75 MHz): d¼41.9, 47.7, 116.8,
128.4, 128.6, 129.8, 134.9. Mass (ESI): m/z 261 (MþNHþ4 ).
HRMS (ESI): Anal. Calcd for C9H9N2O2NaSCl: 266.9970.
Found: 266.9972.
4.3.13. N-[Cyano-(4-methoxyphenyl)methyl]methanesulfon-
amide (2p)
4.4.1. N-[1-Cyano-(4-methoxyphenyl)ethyl]benzenesulfon-
amide (4g)
Rf 0.45 (hexane/EtOAc 5:5), white solid; mp 143e144 ꢁC.
Rf 0.46 (hexane/EtOAc 5:5), colourless solid; mp
IR (KBr): 3206, 2244, 1315, 1157, 1073 cmꢀ1
.
1H NMR
151e153 ꢁC. IR (KBr): 3269, 2249, 1342, 1156, 1091 cmꢀ1
.
(CDCl3, 300 MHz): d¼3.13 (s, 3H), 3.83 (s, 3H), 4.75 (d,
J¼8.7 Hz, 1H), 5.5 (d, J¼8.7 Hz, 1H), 6.93 (d, J¼8.3 Hz,
2H), 7.45 (d, J¼8.3 Hz, 2H). 13C NMR (CDCl3, 75 MHz):
1H NMR (CDCl3, 300 MHz): d¼1.94 (s, 3H), 3.8 (s, 3H),
5.28 (s, 1H), 6.77 (d, J¼8.9 Hz, 2H), 7.36 (d, J¼8.9 Hz,
2H), 7.42e7.58 (m, 3H), 7.73 (d, J¼8.1 Hz, 2H). 13C NMR

M.L. Kantam et al. / Tetrahedron 64 (2008) 3351e3360
3359
(CDCl3, 75 MHz): d¼30.1, 55.4, 56.1, 114.0, 119.2, 127.1,
127.3, 128.6, 128.9, 132.9, 140.1, 160.1. Mass (ESI): m/z 339
(MþNaþ). HRMS (ESI): Anal. Calcd for C16H16N2O3NaS:
339.0779. Found: 339.0766.
d¼24.2, 29.6, 61.3, 62.0, 116.3, 125.0, 126.4, 126.7, 127.1,
129.3, 129.5, 132.8, 135.7, 141.1, 145.6. Mass (ESI): m/z 352
(MþNaþ). HRMS (ESI): Anal. Calcd for C17H19N3O2NaS:
352.1044. Found: 352.1031.
4.4.2. N-[(E)-1-Cyano-1-methyl-3-phenyl-2-propenyl]-
benzenesulfonamide (4h)
Rf 0.43 (hexane/EtOAc 6:4), colourless solid; mp
126e127 ꢁC. IR (KBr): 3252, 2238, 1338, 1163, 1122 cmꢀ1
4.4.7. N-[1-Cyano-1-(3-pyridyl)ethyl]-2-methyl-2-propane-
sulfonamide (4m)
Rf 0.52 (hexane/EtOAc 6:4), brown solid; mp 98e100 ꢁC.
1
IR (KBr): 3228, 2244, 1306, 1126 cmꢀ1. H NMR (CDCl3,
.
1H NMR (CDCl3, 300 MHz): d¼1.8 (s, 3H), 5.41 (s, 1H),
5.89 (d, J¼16.2 Hz, 1H), 6.83 (d, J¼16.2 Hz, 1H),
7.29e7.32 (m, 5H), 7.47 (t, J¼7.6 Hz, 2H), 7.58 (t,
J¼7.6 Hz, 1H), 7.85 (d, J¼7.6 Hz, 2H). 13C NMR (CDCl3,
75 MHz): d¼28.5, 54.5, 118.2, 125.3, 127.0, 127.7, 128.6,
128.9, 129.1, 133.2, 133.3, 134.4, 140.1. Mass (ESI): m/z 335
(MþNaþ). HRMS (ESI): Anal. Calcd for C17H16N2O2NaS:
335.0830. Found: 335.0834.
300 MHz): d¼1.38 (s, 9H), 1.99 (s, 3H), 6.11 (s, 1H), 7.28
(t, J¼6.1 Hz, 1H), 7.69e7.8 (m, 2H), 8.51 (d, J¼6.1 Hz,
1H). 13C NMR (CDCl3, 75 MHz): d¼24.1, 30.6, 40.8, 57.1,
60.7, 120.1, 124.0, 138.1, 148.8, 156.1. Mass (ESI): m/z 290
(MþNaþ). HRMS (ESI): Anal. Calcd for C12H17N3O2NaS:
290.0939. Found: 290.0943.
4.4.8. N-[1-Cyano-1-methylpentyl]-2-methyl-2-propane-
sulfonamide (4n)
Rf 0.44 (hexane/EtOAc 6:4), colourless solid; mp
110e112 ꢁC. IR (KBr): 3268, 2227, 1301, 1124 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz): d¼0.97 (t, J¼6.8 Hz, 3H),
1.35e1.41 (m, 2H), 1.44 (s, 9H), 1.47e1.59 (m, 2H), 1.75
(s, 3H), 1.8e1.87 (m, 1H), 1.92e2.03 (m, 1H), 4.71 (br s,
1H). 13C NMR (CDCl3, 75 MHz): d¼13.7, 22.2, 24.2, 26.4,
27.2, 41.5, 54.2, 60.6, 120.3. Mass (ESI): m/z 269 (MþNaþ).
HRMS (ESI): Anal. Calcd for C11H22N2O2NaS: 269.1299.
Found: 269.1289.
4.4.3. N-(Cyanophenylethyl)methanesulfonamide (4i)
Rf 0.42 (hexane/EtOAc 5:5), colourless solid; mp 81e82 ꢁC.
1
IR (KBr): 3258, 2242, 1329, 1165 cmꢀ1. H NMR (CDCl3,
300 MHz): d¼1.96 (s, 3H), 2.81 (s, 3H), 6.3 (s, 1H), 7.37e
7.46 (m, 3H), 7.62e7.64 (d, J¼7.6 Hz, 2H). 13C NMR
(CDCl3, 75 MHz): d¼30.4, 42.5, 56.5, 119.6, 125.5, 129.1,
129.5, 137.5. Mass (ESI): m/z 247 (MþNaþ). HRMS (ESI):
Anal. Calcd for C10H12N2O2NaS: 247.0517. Found: 247.0514.
4.4.4. N-[1-Cyano-(2-naphthyl)ethyl]-2-methyl-2-propane-
sulfonamide (4j)
4.5. Typical procedure for the Strecker reaction of ketoimine
3a with ethyl cyanoformate
Rf 0.4 (hexane/EtOAc 6:4), white solid; mp 142e144 ꢁC. IR
(KBr): 3283, 2232, 1304, 1157 cmꢀ1 1H NMR (CDCl3,
.
300 MHz): d¼1.45 (s, 9H), 2.16 (s, 3H), 4.54 (s, 1H), 7.5e7.56
(m, 2H), 7.64 (d, J¼9.1 Hz, 1H), 7.81e7.92 (m, 3H), 8.12 (s,
1H). 13C NMR (CDCl3, 75 MHz): d¼24.2, 30.0, 57.4, 61.0,
119.8, 122.1, 124.9, 127.0, 127.2, 127.6, 128.5, 129.4, 132.8,
133.2, 136.1. Mass (ESI): m/z 334 (MþNHþ4 ). HRMS (ESI):
Anal. Calcd for C17H20N2O2NaS: 339.1143. Found: 339.1131.
Ethyl cyanoformate (2 mmol) was added to a stirred solu-
tion of NAP-MgO (0.05 g) and ketoimine 3a (1 mmol) in
3 mL of DMF at room temperature, followed by addition of
acetic acid (2 mmol). Reaction was monitored by thin layer
chromatography (TLC), after 3 h of stirring no product was
present by TLC.
4.4.5. N-[1-Cyano-(4-methylphenyl)phenylmethyl]-2-
methyl-2-propanesulfonamide (4k)
Acknowledgements
Rf 0.36 (hexane/EtOAc 6:4), colourless solid; mp
We wish to thank the CSIR, India for financial support
under the Task Force Project COR-0003. K.M. thanks the
CSIR, India for the award of his research fellowship. K.M.
thanks Dr. A.V.S. Sharma, NMR Division, IICT for providing
13C and 29Si NMR.
153e155 ꢁC. IR (KBr): 3214, 2238, 1314, 1126 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz): d¼1.48 (s, 9H), 2.37 (s, 3H), 4.74
(s, 1H), 7.19 (d, J¼8.3 Hz, 2H), 7.34 (d, J¼9.1 Hz, 2H),
7.38e7.43 (m, 3H), 7.48 (d, J¼8.3 Hz, 2H). 13C NMR
(CDCl3, 75 MHz): d¼21.1, 24.3, 61.3, 64.6, 96.1, 119.1,
126.8, 128.9, 129.2, 129.7, 136.1, 139.2. Mass (ESI): m/z 360
(MþNHþ4 ). HRMS (ESI): Anal. Calcd for C19H22N2O2NaS:
365.1299. Found: 365.1290.
References and notes
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4.4.6. N-[1-Cyano-(phenyl)-3-pyridylmethyl]-2-methyl-2-
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