Synthesis of α-aminonitriles through Strecker reaction of N-tosylaldimines using molecular iodine

Article abstract of DOI:10.1055/s-0029-1216969

The Strecker reaction of N-tosylaldimines with trimethylsilyl cyanide in the presence of catalytic amount of iodine at room, temperature produces the corresponding protected α-aminonitriles in high yields.

Full text of DOI:10.1055/s-0029-1216969

PAPER
3467
Synthesis of a-Aminonitriles through Strecker Reaction of N-Tosylaldimines
Using Molecular Iodine1
S
ynthesis of
a
-A
i
s
riles throu
w
gh
S
trecker
R
eact
a
ionof
N
-
To
n
sylaldimine
s
ath Das,* Penagaluri Balasubramanyam, Maddeboina Krishnaiah, Boyapati Veeranjaneyulu,
Gandolla Chinna Reddy
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: biswanathdas@yahoo.com
Received 6 May 2009; revised 9 June 2009
Table 1 Evaluation of the Catalytic Activity of Different Catalysts
for the Preparation of a-Aminonitrile 3aa
Abstract: The Strecker reaction of N-tosylaldimines with trimeth-
ylsilyl cyanide in the presence of catalytic amount of iodine at room
temperature produces the corresponding protected a-aminonitriles
in high yields.
Ts
Ts
catalyst (15 mol%)
CH2Cl2, r.t.
N
HN
+
TMSCN
H
CN
Key words: Strecker reaction, N-tosylaldimine, trimethylsilyl cya-
nide, protected a-aminonitrile, iodine
1a
2
3a
Entry
Catalyst
I2
Time (h)
Yieldb (%)
a-Aminonitriles are useful intermediates for the prepara-
tion of a-amino acids,2 various nitrogen containing het-
erocycles, such as imidazoles and thiadiazoles,3 and
pharmaceuticals.4,5b a-Amino acids are highly applicable
in chemistry and biology as valuable building blocks.5
The Strecker reaction involving nucleophilic addition of a
cyanide ion to an imine, is of great importance to modern
organic chemistry as it offers one of the most direct feasi-
ble methods for the synthesis of a-aminonitriles.6 Howev-
er the experimental procedure of this reaction is tedious.
Several modified methods have been subsequently intro-
duced using various cyanide reagents [e.g. diethyl phos-
1
2
3
4
5
6
1.0
3.5
3.5
4.0
4.0
4.0
94
FeCl3
ZrCl4
CuI
85
82
78
ZnCl2
SnCl2
53
trace
a Conditions: N-tosylaldimine 1a (1.0 mmol), TMSCN 2 (1.3 mmol),
catalyst (15 mol%), CH2Cl2 (2 mL), r.t.
phorocyanidate, a-(trimethylsiloxy)nitrile, tributyltin b Isolated yield.
cyanide, trimethylsilyl cyanide, etc.].7 Among these cya-
nide ion equivalents, trimethylsilyl cyanide was found to
There have numerous reports in recent years on the appli-
be more efficient and safer in handling.
cation of N-sulfonyl- and N-sulfinylimines, which are sta-
ble compounds.14 These sulfonyl and sulfinyl groups are
good activators of the C=N bond for nucleophilic addition
reactions. Therefore, the addition of trimethylsilyl cya-
nide to these compounds is expected to be a good method
for obtaining a-aminonitriles. There are only a few reports
on the Strecker reaction of N-sulfonylimines using N-het-
erocyclic carbenes,15a,b Feng’s bifunctional N,N1-diox-
ide,15c Lewis acids and bases,8b,9b and Nap-MgO.15d
However, many of these methods suffer from different
drawbacks such as requirement for longer reaction times,
application of costly reagents, harsh reaction conditions,
and unsatisfactory yields.
The Strecker reaction has been studied extensively by us-
ing various Lewis acids,8 Lewis bases,9 N-heterocyclic
carbenes,10 and metal complexes and metal–salen com-
plexes.11 Recently, a number of asymmetric Strecker reac-
tions using effective catalysts have been reported.12
Ts
NHTs
N
I2 (15 mol%)
TMSCN
+
CH2Cl2, r.t.
60–90 min
CN
R
H
R
3
1
2
86–94%
R = aryl, alkyl
Scheme 1 Synthesis of a-aminonitriles by the reaction of N-tosyl-
aldimines and trimethylsilyl cyanide
In continuation of our work on the development of useful
synthetic methodologies we have observed that protected
a-aminonitriles 3 can efficiently be synthesized by treat-
ment of N-sulfonylaldimines 1 with trimethylsilyl cyanide
(2) in the presence of iodine as a catalyst at room temper-
ature (Scheme 1).
a-Aminonitriles have also been synthesized by employing
Strecker methodology using ionic liquids and water in-
stead of regular organic solvents.8a,13
Initially we carried out the reaction of N-tosylbenzald-
imine (1a) with trimethylsilyl cyanide (2) in the presence
of various catalysts. However, considering the reaction
time and yield iodine was found to be most effective
SYNTHESIS 2009, No. 20, pp 3467–3471
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216969; Art ID: Z08909SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
9

3468
B. Das et al.
PAPER
(Table 1). Finally a series of protected a-aminonitriles 3 In conclusion, we have developed a facile method for the
were prepared (Table 2) from different N-tosylaldimines synthesis of a-aminonitriles from N-tosylaldimines and
214a,c,16 derived from various aromatic, heteroaromatic, trimethylsilyl cyanide using iodine as a catalyst. The op-
and aliphatic aldehydes using trimethylsilyl cyanide (2) in erational simplicity, mild reaction conditions, application
the presence of iodine. The aromatic aldehydes contained of an easily available catalyst, short reaction times and ex-
both electron-donating as well as electron-withdrawing cellent yields are the notable advantages of the method.
groups (Table 1, entries 2–12). The aliphatic aldimine de- The tosyl group of the products can also easily be depro-
rivatives (Table 2, entries 15 and 16) also underwent tected to free amines, which can be utilized for the prepa-
smooth conversion into a-aminonitriles. The reaction was ration of various desired analogues.
conducted at room temperature and the conversion was
complete within 60–90 minutes and the protected a-ami-
Melting points were measured on a Buchi 510 apparatus and are un-
nonitriles 3 were formed in excellent yields (86–94%).
The structures of the products 3 were confirmed by their
spectral (IR, 1H and 13C NMR, and MS) data. The N-tosyl
group of the products can easily be deprotected17 to fur-
nish the corresponding a-aminonitriles which can be used
to explore their biological applications.
corrected. The IR spectra were recorded with KBr on a Perkin-
Elmer RX 1 FT-IR spectrophotometer; the NMR spectra on a Varian
Gemini-200 MHz spectrometer using CDCl3 as a solvent and TMS
as an internal standard; and the mass spectra on a VG Micromass
7070 H (70 eV) and Thermo Finnegan LCQ ion trap mass spectro-
meters. Column chromatography was performed over silica gel
(BDH, 100–200 mesh) and TLC on silica gel GF 254.
The catalyst, iodine is inexpensive, easily available, and
nontoxic. It efficiently conducts the nucleophilic addition
of N-sulfonylimines by polarizing the CH=N bond of the
compounds.
a-Aminonitriles 3; General Procedure
Tosylimine 1 (1 mmol) was taken in CH2Cl2 (2 mL) and I2 (15
mol%) was added. To this mixture TMSCN 2 (1.3 mmol) was added
dropwise. The mixture was stirred at r.t. (TLC monitoring). After
completion the reaction was quenched with sat. Na2S2O3 soln (10
mL) and the mixture was extracted with CH2Cl2 (3 × 10 mL). The
combined extracts were dried and concentrated and the residue was
subjected to column chromatography (silica gel, hexane–EtOAc) to
obtain pure a-aminonitrile 3.
Table 2 Iodine-Catalyzed Synthesis of a-Aminonitriles 3 by the
Reaction of N-Tosylaldimines 1 and Trimethylsilyl Cyanide (2)a
Ts
NHTs
N
I2 (15 mol%)
TMSCN
+
N-[Cyano(phenyl)methyl]-4-methylbenzenesulfonamide (3a)
Mp 151–153 °C.
CH2Cl2, r.t.
60–90 min
CN
H
R
R
1
2
3
IR: 3264, 2310, 1597, 1448, 1333, 1156 cm–1.
R = aryl, alkyl
86–94 %
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.49–
7.36 (m, 7 H), 5.60 (d, J = 10.0 Hz, 1 H), 5.47 (d, J = 10.0 Hz, 1 H),
2.49 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.8, 136.1, 132.2, 130.0, 129.9,
129.4, 127.3, 127.1, 116.5, 48.3, 21.9.
Entry
1
R
Time (min) Product
Yieldb (%)
94
Ph
60
60
60
70
80
80
90
90
90
80
80
90
90
80
60
60
3a
3b
3c
3d
3e
3f
2
3-ClC6H4
4-ClC6H4
4-F-3-ClC6H3
2,3,4-F3C6H2
4-O2NC6H4
4-MeOC6H4
4-BnOC6H4
4-EtOC6H4
4-MeC6H4
2,5-Me2C6H3
2,4,6-Me3C6H2
2-furyl
92
3
93
MS (ESI): m/z = 309 [M + Na]+.
Anal. Calcd for C15H14N2O2S: C, 62.93; H, 4.89; N, 9.79. Found: C,
62.86; H, 4.97; N, 9.84.
4
92
5
90
N-[3-Chlorophenyl)(cyano)methyl]-4-methylbenzenesulfon-
amide (3b)
Mp 101–103 °C.
IR: 3278, 2237, 1596, 1437, 1349, 1161 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.78 (d, J = 8.0 Hz, 2 H), 7.40–
7.31 (m, 6 H), 5.59 (d, J = 10.0 Hz, 1 H), 5.39 (d, J = 10.0 Hz, 1 H),
2.48 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 145.0, 135.8, 135.3, 133.9, 130.8,
130.1, 130.0, 127.1, 125.2, 116.0, 47.8, 21.9.
6
91
7
3g
3h
3i
88
8
89
9
90
10
11
12
13
14
15
16
3j
92
3k
3l
90
MS (ESI): m/z = 343, 345 [M + Na]+.
88
Anal. Calcd for C15H13ClN2O2S: C, 56.26; H, 4.06; N, 8.74. Found:
C, 56.31; H, 4.13; N, 8.62.
3m
3n
3o
3p
86
2-thienyl
89
N-[(4-Chlorophenyl)(cyano)methyl]-4-methylbenzenesulfon-
amide (3c)
Mp 133–135 °C.
IR: 3261, 1925, 1594, 1491, 1342, 1159 cm–1.
Et
91
Pr
90
1H NMR (200 MHz, CDCl3): d = 7.77 (d, J = 8.0 Hz, 2 H), 7.43–
7.31 (m, 6 H), 5.81 (d, J = 10.0 Hz, 1 H), 5.41 (d, J = 10.0 Hz, 1 H),
2.48 (s, 3 H).
a Reaction conditions: N-tosylaldimine 1 (1.0 mmol), TMSCN 2 (1.3
mmol), I2 (15 mol%), CH2Cl2 (2 mL), r.t.
b Isolated yield.
Synthesis 2009, No. 20, 3467–3471 © Thieme Stuttgart · New York

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Synthesis of a-Aminonitriles through Strecker Reaction of N-Tosylaldimines
3469
13C NMR (50 MHz, CDCl3): d = 148.9, 136.1, 136.0, 130.9, 130.5,
129.8, 128.2, 127.6, 116.0, 47.7, 21.5.
Anal. Calcd for C16H16N2O3S: C, 60.76; H, 5.06; N, 8.86. Found: C,
60.85; H, 5.13; N, 8.78.
MS (ESI): m/z = 343, 345 [M + Na]+.
N-{[4-(Benzyloxy)phenyl](cyano)methyl}-4-methylbenzene-
sulfonamide (3h)
Mp 164–166 °C.
Anal. Calcd for C15H13ClN2O2S: C, 56.25; H, 4.06; N, 8.73. Found:
C, 56.22; H, 4.11; N, 8.79.
IR: 3258, 2238, 1606, 1513, 1329, 1247 cm–1.
N-[(3-Chloro-4-fluorophenyl)(cyano)methyl]-4-methylben-
zenesulfonamide (3d)
Mp 124–125 °C.
IR: 3279, 1597, 1499, 1443, 1345, 1159 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.74 (d, J = 8.0 Hz, 2 H), 7.42 (dd,
J = 8.0, 2.0 Hz, 1 H), 7.35 (d, J = 2.0 Hz, 1 H), 7.32 (d, J = 8.0 Hz,
2 H), 7.12 (t, J = 8.0 Hz, 1 H), 5.92 (d, J = 10.0 Hz, 1 H), 5.41 (d,
J = 10.0 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 157.0, 145.0, 135.9, 130.2, 130.0,
129.6, 127.1, 122.0 (d, J = 8.0 Hz), 117.5 (d, J = 8.0 Hz), 115.7,
47.1, 21.5.
1H NMR (200 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.46–
7.31 (m, 9 H), 6.98 (d, J = 8.0 Hz, 2 H), 5.41 (d, J = 10.0 Hz, 1 H),
5.17 (d, J = 10.0 Hz, 1 H), 5.05 (s, 2 H), 2.46 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 158.8, 145.5, 136.1, 130.1, 128.9,
128.8, 127.3, 124.6, 115.8, 70.1, 48.0, 21.8.
MS (ESI): m/z = 415 [M + Na]+.
Anal. Calcd for C22H20N2O3S: C, 67.35; H, 5.10; N, 7.14. Found: C,
67.52; H, 5.04; N, 7.28.
N-[Cyano(4-ethoxyphenyl)methyl]-4-methylbenzenesulfon-
amide (3i)
Mp 112–114 °C.
IR: 3279, 2250, 1607, 1513, 1337, 1256 cm–1.
MS (ESI): m/z = 361, 363 [M + Na]+.
Anal. Calcd for C15H12ClFN2O2S: C, 53.25; H, 3.55; N, 8.28.
Found: C, 53.32; H, 3.46; N, 8.21.
1H NMR (200 MHz, CDCl3): d = 7.79 (d, J = 8.0 Hz, 2 H), 7.32 (d,
J = 8.0 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H), 6.83 (d, J = 8.0 Hz, 2
H), 5.60 (br s, 1 H), 5.36 (d, J = 8.0 Hz, 1 H), 4.00 (q, J = 7.0 Hz,
2 H), 2.43 (s, 3 H), 1.41 (t, J = 7.0 Hz, 3 H).
N-[Cyano(2,3,4-trifluorophenyl)methyl]-4-methylbenzene-
sulfonamide (3e)
Mp 96–98 °C.
IR: 3253, 2240, 1600, 1512, 1348, 1153 cm–1.
13C NMR (50 MHz, CDCl3): d = 159.9, 144.5, 136.2, 130.0, 128.5,
127.4, 124.0, 116.9, 115.2, 63.9, 47.9, 21.6, 14.6.
1H NMR (200 MHz, CDCl3): d = 7.72 (d, J = 8.0 Hz, 2 H), 7.38–
7.19 (m, 3 H), 7.00 (m, 1 H), 5.92 (d, J = 10.0 Hz, 1 H), 5.57 (d,
J = 10.0 Hz, 1 H), 2.45 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 145.0, 135.9, 130.1, 127.2, 123.0,
122.9, 118.0, 117.9, 116.1, 113.1, 113.0, 42.4, 21.9.
MS (ESI): m/z = 353 [M + Na]+.
Anal. Calcd for C17H18N2O3S: C, 61.82; H, 5.46; N, 8.49. Found:
C, 61.94; H, 5.52; N, 8.54.
N-[Cyano(p-tolyl)methyl]-4-methylbenzenesulfonamide (3j)
Mp 154–156 °C.
IR: 3269, 2250, 1596, 1437, 1335, 1159 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.38 (d,
J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.19 (d, J = 8.0 Hz, 2 H),
5.42 (d, J = 10.0 Hz, 1 H), 5.01 (d, J = 10.0 Hz, 1 H), 2.50 (s, 3 H),
2.39 (s, 3 H).
MS (ESI): m/z = 363 [M + Na]+.
Anal. Calcd for C15H11F3N2O2S: C, 52.94; H, 3.24; N, 8.24. Found:
C, 52.82; H, 3.19; N, 8.17.
N-[Cyano(4-nitrophenyl)methyl]-4-methylbenzenesulfon-
amide (3f)
Mp 120–122 °C.
IR: 3261, 1920, 1600, 1531, 1459, 1347, 1161 cm–1.
13C NMR (50 MHz, CDCl3): d = 144.9, 140.2, 136.0, 130.0, 129.1,
127.2, 127.0, 116.5, 48.1, 21.7, 21.1.
1H NMR (200 MHz, CDCl3): d = 8.26 (d, J = 8.0 Hz, 2 H), 7.78 (d,
J = 8.0 Hz, 2 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.38 (d, J = 8.0 Hz, 2 H),
5.55 (d, J = 10.0 Hz, 1 H), 5.36 (d, J = 10.0 Hz, 1 H), 2.7 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 148.7, 145.3, 138.6, 135.5, 130.3,
128.4, 127.3, 124.5, 115.6, 47.5, 21.7.
MS (ESI): m/z = 323 [M + Na]+.
Anal. Calcd for C16H16N2O2S: C, 64.00; H, 5.33; N, 9.34. Found: C,
64.08; H, 5.25; N, 9.41.
N-[Cyano(2,5-dimethylphenyl)methyl]-4-methylbenzene-
sulfonamide (3k)
Mp 137–139 °C.
IR: 3268, 2217, 1596, 1332, 1157 cm–1.
MS (ESI): m/z = 354 [M + Na]+.
Anal. Calcd for C15H13N3O4S: C, 54.39; H, 3.93; N, 12.69. Found:
C, 54.30; H, 3.99; N, 12.76.
N-[Cyano(4-methoxyphenyl)methyl]-4-methylbenzenesulfon-
amide (3g)
Mp 128–130 °C.
IR: 3269, 2320, 1606, 1512, 1437, 1252, 1158 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.70 (d, J = 8.0 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 6.88 (d, J = 8.0 Hz, 2 H),
5.58 (d, J = 10.0 Hz, 1 H), 5.39 (d, J = 10.0 Hz, 1 H), 3.79 (s, 3 H),
2.45 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 160.4, 144.5, 136.2, 130.0, 128.4,
127.2, 124.0, 116.8, 114.9, 55.8, 47.9, 21.8.
1H NMR (200 MHz, CDCl3): d = 7.80 (d, J = 8.0 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 7.22 (dd, J = 8.0, 2.0 Hz, 1 H), 7.08 (br s, 2 H),
5.51 (d, J = 10.0 Hz, 1 H), 4.89 (d, J = 10.0 Hz, 1 H), 2.49 (s, 3 H),
2.38 (s, 3 H), 2.31 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.5, 136.8, 136.2, 133.1, 131.6,
130.8, 129.9, 128.2, 127.3, 116.8, 46.0, 21.5, 21.0, 18.2.
MS (ESI): m/z = 337 [M + Na]+.
Anal. Calcd for C17H18N2O2S: C, 64.97; H, 5.73; N, 8.91. Found: C,
64.83; H, 5.82; N, 8.84.
N-[Cyano(mesityl)methyl]-4-methylbenzenesulfonamide (3l)
Mp 139–140 °C.
MS (ESI): m/z = 339 [M + Na]+.
Synthesis 2009, No. 20, 3467–3471 © Thieme Stuttgart · New York

3470
B. Das et al.
PAPER
IR: 3277, 1601, 1416, 1334, 1161 cm–1.
Acknowledgment
1H NMR (200 MHz, CDCl3): d = 7.76 (d, J = 8.0 Hz, 2 H), 7.28 (d,
J = 8.0 Hz, 2 H), 6.81 (s, 2 H), 5.64 (d, J = 8.0 Hz, 1 H), 5.52 (br s,
1 H), 2.42 (s, 3 H), 2.31 (s, 6 H), 2.22 (s, 3 H).
The author thanks CSIR and UGC, New Delhi for financial assis-
tance.
13C NMR (50 MHz, CDCl3): d = 144.8, 139.8, 136.7, 136.0, 130.2,
130.0, 127.3, 126.1, 116.8, 42.9, 21.2, 20.5, 19.9.
References
MS (ESI): m/z = 351 [M + Na]+.
(1) Part 187 in the series, Studies on Novel Synthetic
Methodologies.
Anal. Calcd for C18H20N2O2S: C, 65.85; H, 6.10; N, 8.54. Found: C,
65.72; H, 6.18; N, 8.63.
(2) (a) Shafran, Y. M.; Bakulev, V. A.; Mokrushin, V. S. Russ.
Chem. Rev. 1989, 58, 148. (b) March, J. Advanced Organic
Chemistry, 4th ed.; Wiley: New York, 1999, 965.
(3) (a) Weinstock, L. M.; Davis, P.; Handlesman, B.; Tull, R.
J. Org. Chem. 1967, 32, 2823. (b) Matier, W. L.; Owens, D.
A.; Comer, W. T.; Deitchman, D.; Ferguson, H. C.;
Seidehamel, R. J.; Young, J. R. J. Med. Chem. 1973, 16, 901.
(4) (a) Chemistry and Biochemistry of the Amino Acids; Barrett,
G. C., Ed.; Chapman & Hall: London, 1985. (b) Coppala,
G. M.; Schuster, H. F. Asymmetric Synthesis Construction of
Chiral Molecules Using Amino Acids; Wiley: New York,
1987, and references cited therein.
N-[Cyano(2-furyl)methyl]-4-methylbenzenesulfonamide (3m)
Mp 99–101 °C.
IR: 3113, 1465, 1330, 1241, 1161 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.79 (d, J = 8.0 Hz, 2 H), 7.38 (d,
J = 8.0 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 6.48 (m, 1 H), 6.32 (m,
1 H), 5.70 (m, 1 H), 5.52 (d, J = 8.0 Hz, 1 H), 2.43 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.9, 144.5, 144.2, 135.9, 130.1,
127.2, 114.8, 111.1, 110.7, 42.2, 21.7.
MS (ESI): m/z = 299 [M + Na]+.
(5) (a) Duthaler, R. O. Tetrahedron 1994, 50, 1539. (b)Enders,
D.; Shilvock, P. Chem. Soc. Rev. 2000, 29, 359.
Anal. Calcd for C13H12N2O3S: C, 56.52; H, 4.35; N, 10.14. Found:
C, 56.61; H, 4.43; N, 10.07.
(6) (a) Strecker, A. Ann. Chem. Pharm. 1850, 75, 27. (b) Yet,
L. Angew. Chem. Int. Ed. 2001, 40, 875. (c) Groger, H.
Chem. Rev. 2003, 103, 2795.
N-[Cyano(2-thienyl)methyl]-4-methylbenzenesulfonamide (3n)
(7) (a) Harusawa, S.; Hamada, Y.; Shioiri, T. Tetrahedron Lett.
1979, 20, 4663. (b) Mai, K.; Patil, G. Tetrahedron Lett.
1984, 25, 4583. (c) Kobayashi, S.; Ishitani, H. Chem. Rev.
1999, 99, 1069. (d) Davis, F. A.; Lee, S.; Zhang, H.; Fanelli,
D. L. J. Org. Chem. 2000, 65, 8704. (e) Mori, Y.; Kimura,
M.; Seki, M. Synthesis 2003, 2311. (f) Nakamura, S.; Sato,
N.; Sugimoto, M.; Toru, T. Tetrahedron: Asymmetry 2004,
15, 1513. (g) Herrera, R. P.; Sagarzani, V.; Bernardi, L.;
Fini, F.; Pettersen, D.; Ricci, A. J. Org. Chem. 2006, 71,
9869.
Mp 113–115 °C.
IR: 3238, 2217, 1600, 1333 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.81 (d, J = 8.0 Hz, 2 H), 7.40–
7.34 (m, 3 H), 7.20 (m, 1 H), 6.98 (m, 1 H), 5.79 (d, J = 10.0 Hz, 1
H), 5.65 (d, J = 10.0 Hz, 1 H), 2.46 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 145.0, 136.2, 134.9, 130.2, 130.0,
128.2, 128.0, 127.3, 127.2, 126.4, 115.8, 43.9, 21.5.
MS (ESI): m/z = 315 [M + Na]+.
(8) (a) Kobayashi, S.; Busujima, T.; Nagayama, S. Chem.
Commun. 1998, 981. (b) Bhanu Prasad, B. A.; Bisai, A.;
Singh, V. K. Tetrahedron Lett. 2004, 45, 9565. (c) Royer,
L.; De S, K.; Gibbs, R. A. Tetrahedron Lett. 2005, 46, 4595.
(d) Surya Prakash, G. K.; Mathew, T.; Panja, C.; Alconcel,
S.; Vaghoo, H.; Do, C.; Olah, G. A. Proc. Natl. Acad. Sci.
U.S.A. 2007, 104, 3703.
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Wang, Q. R.; Hou, X. L. J. Org. Chem. 2003, 68, 6264.
(b) Takahashi, E.; Fujisawa, H.; Yanai, T.; Mukaiyama, T.
Chem. Lett. 2005, 34, 318. (c) Fetterly, B. M.; Jana, N. K.;
Verkade, J. G. Tetrahedron 2006, 62, 440.
(10) (a) Groger, H. Chem. Eur. J. 2001, 7, 5247. (b) Shibasaki,
M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187.
(c) Tsogoeva, S. B.; Heteley, M. J.; Yalalov, D. A.; Meindl,
K.; Weckbecker, C.; Huthmacher, K. Bioorg. Med. Chem.
2005, 13, 5680.
Anal. Calcd for C13H12N2O2S2: C, 53.43; H, 4.11; N, 9.59. Found:
C, 53.58; H, 4.17; N, 9.48.
N-(1-Cyanopropyl)-4-methylbenzenesulfonamide (3o)
Mp 81–83 °C.
IR: 3269, 2249, 1599, 1441, 1338, 1169 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.80 (d, J = 8.0 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 5.80 (br s, 1 H), 4.15 (q, J = 7.0 Hz, 1 H), 2.45 (s,
3 H), 1.88–1.76 (m, 2 H), 1.05 (t, J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.5, 136.0, 130.1, 127.3, 117.5,
45.6, 27.4, 21.5, 9.8.
MS (ESI): m/z = 261 [M + Na]+.
Anal. Calcd for C11H14N2O2S: C, 55.46; H, 5.88; N, 11.76. Found:
C, 55.38; H, 5.99; N, 11.84.
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W. G.; Gleason, J. D.; Snapper, M. L.; Hoveyda, A. H.
J. Am. Chem. Soc. 1999, 121, 4284. (b) Banphavichit, V.;
Mansawat, W.; Bhanthumnavin, W.; Vilaivan, T.
Tetrahedron 2004, 60, 10559. (c) Blacker, J.; Clutterbuck,
L. A.; Crampton, M. R.; Grosjean, C.; North, M.
Tetrahedron: Asymmetry 2006, 17, 1449.
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J. Am. Chem. Soc. 1996, 118, 4910. (b) Corey, E. J.;
Grogan, M. Org. Lett. 1999, 1, 157. (c) Sigman, M. S.;
Vachal, P.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2000, 39,
1279. (d) Liu, B.; Feng, X.; Chen, F.; Zhang, G.; Cui, X.;
Jiang, Y. Synlett 2001, 1551.
N-(1-Cyanobutyl)-4-methylbenzenesulfonamide (3p)
Mp 84–86 °C.
IR: 3282, 2242, 1597, 1424, 1334, 1160 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.80 (d, J = 8.0 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 5.69 (br s, 1 H), 4.21 (q, J = 7.0 Hz, 1 H), 2.45 (s,
3 H), 1.81–1.72 (m, 2 H), 1.52–1.40 (m, 2 H), 0.92 (t, J = 7.0 Hz, 3
H).
13C NMR (50 MHz, CDCl3): d = 144.5, 136.0, 129.9, 127.0, 117.6,
44.0, 35.8, 21.7, 18.4, 13.0.
MS (ESI): m/z = 275 [M + Na]+.
Anal. Calcd for C12H16N2O2S: C, 57.14; H, 6.35; N, 11.11. Found:
C, 57.21; H, 6.47; N, 11.04.
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Synthesis of a-Aminonitriles through Strecker Reaction of N-Tosylaldimines
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Synthesis 2009, No. 20, 3467–3471 © Thieme Stuttgart · New York