Conversion of N-benzyloxycarbonylamino- and N-Tosylamino-benzyl phenylsulfones by green Strecker reactions to α-aminobenzyl nitriles using potassium hexacyanoferrate(II)

Article abstract of DOI:10.3184/174751914X14030207593683

The cyanation of aldimines, generated in situ from N- benzyloxycarbonylamino- and N-tosylamino-benzyl phenylsulfones, to the corresponding N-protected a-aminobenzyl nitriles has been achieved by eco-friendly Strecker reactions using potassium hexacyanofer

Full text of DOI:10.3184/174751914X14030207593683

432 RESEARCH PAPER
VOL. 38 JULY, 432–436
JOURNAL OF CHEMICAL RESEARCH 2014
Conversion of N‑benzyloxycarbonylamino‑ and N‑tosylamino‑benzyl
phenylsulfones by green Strecker reactions to α‑aminobenzyl nitriles using
potassium hexacyanoferrate(II)
Xiaochun Hua,b, Rongzhi Lia and Zheng Lia*
aCollege of Chemistry and Chemical Engineering, bEditorial Department of the University Journal, Northwest Normal University, Lanzhou, Gansu,
730070, P.R. China
The cyanation of aldimines, generated in situ from N‑benzyloxycarbonylamino‑ and N‑tosylamino‑benzyl phenylsulfones, to
the corresponding N‑protected α‑aminobenzyl nitriles has been achieved by eco‑friendly Strecker reactions using potassium
hexacyanoferrate(II) as a cyanide source, benzoyl chloride as a promoter, and potassium hydroxide as a base. The protocol has
the advantages of using a nontoxic, nonvolatile and inexpensive cyanating agent, employing a simple work‑up procedure and
producing high yields.
Keywords: N‑benzyloxycarbonylaminobenzyl phenylsulfone, N‑tosylaminobenzyl phenylsulfone, potassium hexacyanoferrate(II),
α‑aminobenzyl nitrile, green Strecker reaction
The Strecker reaction, now understood as the nucleophilic
addition of cyanide ion to imines, is of great importance to
modern organic chemistry as it offers one of the most direct
and viable methods for the synthesis of α‑aminonitriles.1
α‑Amido sulfones, which are considered as a useful precursor
of N‑protected imines2 and therefore can directly participate in
Strecker reactions under appropriate conditions, can be easily
prepared by a three‑component coupling of the corresponding
aldehyde, sodium sulfinate and carbamate in the presence
of formic acid.3 Under basic conditions, α‑amido sulfones
are readily converted to N‑protected imines that can further
react with various nucleophiles.4,5 Recently several authors
demonstrated Strecker reactions of α‑amido sulfones using
different cyanide sources. Ooi6 and Reingruber7 reported
the synthesis of N‑p‑tolylsulfonyl α‑amino nitriles from
α‑amido p‑tolylsulfones using aqueous potassium cyanide in
the presence of a phase transfer catalyst. Herrear8 described
Strecker reactions of α‑amido p‑tolylsulfones to synthesise N‑t‑
butyloxycarbonyl α‑amino nitriles using acetone cyanohydrin
as a cyanating agent. Kim9 and Das10 reported the synthesis
of N‑benzyloxycarbonyl α‑amino nitriles from α‑amido
p‑tolylsulfones using trimethylsilyl cyanide as cyanating
agent in the presence of bismuth bromide or indium chloride.
However, some problems are still associated with the use
of these cyanating agents including renowned toxicity of
potassium cyanide, volatility of acetone cyanohydrin, and
moisture unstability of trimethylsilyl cyanide. To overcome
these problems, attention has been given to the development of
alternative cyanide sources that are cheap, less toxic, and easier
to handle.
aroyl cyanides,15 arylsulfonyl cyanide,16 benzyl cyanides,17
and cinnamonitriles.18 Our research work has focused on the
cyanation of unsaturated compounds including C=O,19–22
C=N 23–26 or C=C27–28 bonds by nucleophilic addition reactions
using K4[Fe(CN)6] as an eco‑friendly cyanide source. Here
we report the cyanation of aldimines, generated in situ from
N‑benzyloxycarbonylamino‑
and
N‑tosylamino‑benzyl
phenylsulfones, to the corresponding N‑benzyloxycarbonyl
and N‑tosyl α‑aminobenzyl nitriles by Strecker reactions
using potassium hexacyanoferrate(II) as an eco‑friendly
cyanide source, benzoyl chloride as a promoter, and potassium
hydroxide as a base.
Results and discussion
Initially, N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a
(Scheme 1, R=Ph) was selected as a test substrate to investigate
the Strecker reaction using potassium hexacyanoferrate(II)
(K4[Fe(CN)6]) as an eco‑friendly cyanide source to synthesise
α‑(N‑benzyloxycarbonylamino)benzyl nitrile 2a (Scheme 1,
R=Ph). A preliminary treatment of K4[Fe(CN)6] with benzoyl
chloride (160 °C/3 h) was necessary in order to generate benzoyl
cyanide. Upon cooling this mixture to room temperature, 1a
was added and the mixture stirred in EtOH (10 mL) under
different conditions using various bases. It was found that no
product was given in the absence of a base, nor in the presence
of sodium carbonate (Table 1, entries 1 and 2). Some bases, such
as pyridine and NaOH were totally ineffective. Et3N and DMAP
did give the desired product α‑(N‑benzyloxycarbonylamino)
benzyl nitrile 2a in moderate yield in 7 h (Table 1, entries 3 and
4), but K2CO3 (80%) and KOH (87%) gave very good yields in
just 0.5 h (Table 1, entries 6 and 7).
K4[Fe(CN)6] is a by‑product of the chemical coal industry and
is commercially available on a ton scale, and is cheaper than
KCN. Recently, K4[Fe(CN)6] has been used as a cyanide source
for some substitution reactions to synthesise benzonitriles,11–14
Further research using KOH as a base showed that solvents
also played a crucial role in the Strecker reaction of 1a with
K4[Fe(CN)6] (Table 2). It was found that no product was observed
O
PhO2S
R
CN
O
(i) PhCOCl/160 oC/3 h
(ii) KOH-EtOH/rt
N
O
+ K4[Fe(CN)6]
N
O
R
H
H
2a-n
1a-n
Scheme 1 Cyanation of N‑benzyloxycarbonylaminobenzyl phenylsulfones.
* Correspondent. E‑mail: lizheng@nwnu.edu.cn
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JOURNAL OF CHEMICAL RESEARCH 2014 433
Table 1 The effect of various bases and the duration of reaction on the
yield of cyanation of N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a
by K4[Fe(CN)6](Scheme 1)a
Table 3 The
yields/reaction
times
of
the
cyanation
of
N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a–n using K4[Fe(CN)6]
as a cyanide source (Scheme 1)a
Entry
Base
Time/h
Yield/%b
Entry
R
Product
Time/h
Yield/%b
1
2
3
4
5
6
none
Na2CO3
Et3N
DMAP
K2CO3
KOH
24
24
7
7
0.5
0.5
NRc
NRc
54
40
80
1
2
3
4
5
6
C6H5
2a
2b
2c
2d
2e
2f
4
4
4
4
4
4
87
91
93
95
87
82
2‑CH3C6H4
4‑CH3C6H4
4‑CH3OC6H4
3‑CH3OC6H4
2‑CH3OC6H4
O
87
aReaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2.4 mmol),
N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a (2.0 mmol) and base
(3.0 mmol) in EtOH (10 mL) were stirred at room temperature.
bIsolated yields.
7
2g
4
96
O
8
9
10
11
12
13
4‑FC6H4
2‑FC6H4
2‑ClC6H4
4‑ClC6H4
2,4‑Cl2C6H3
4‑BrC6H4
2h
2i
2j
2k
2l
2m
5
5
5
5
6
6
93
85
91
94
88
88
cUnidentified by‑products were observed.
Table 2 The effect of solvents and the duration of reaction on the yield
of cyanation of N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a by
K4[Fe(CN)6](Scheme 1)a
14
2n
6
63
Entry
Solvent
Time (h)
Yield/%b
O
1
2
3
4
5
6
DMF
Et2O
MeOH
MeCN
CH2Cl2
EtOH
24
24
1
1
2
NRc
NRc
45
51
58
aReaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2.4 mmol),
N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a–n (2.0 mmol) and
potassium hydroxide (3.0 mmol) in EtOH (10 mL) were stirred at room
temperature.
bIsolated yields.
0.5
87
aReaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2.4 mmol),
N‑benzyloxycarbonylaminobenzyl phenylsulfone 1a (2.0 mmol) and
potassium hydroxide (3.0 mmol) in solvent (10 mL) were stirred at room
temperature.
Table 4 The yields/reaction times of the cyanation of N‑tosylaminobenzyl
phenylsulfones 3a–g using K4[Fe(CN)6] as a cyanide source (Scheme 2)a
Entry
R
Product
Time/h
Yield/%b
bIsolated yields.
1
2
3
4
C6H5
4‑CH3C6H4
4‑ClC6H4
4a
4b
4c
4d
3.5
3.5
4
93
95
90
88
cUnidentified by‑products were observed.
2,4‑Cl2C6H3
4
in some solvents, such as PhMe, THF and CHCl3. Reaction in
Et2O and DMF gave unidentified by‑products (Table 2, entries
1 and 2), but reaction in some solvents, such as MeOH, MeCN
and CH2Cl2, gave the desired product in moderate yields
(Table 2, entries 3–5). However, EtOH was found to be the best
solvent for the reaction affording the desired product in the
highest yield within the shortest time (Table 2, entry 6).
Based on the above promising findings, two kinds of α‑amido
sulfones, N‑benzyloxycarbonylaminobenzyl phenylsulfones
(Scheme 1) andN‑tosylaminobenzyl phenylsulfones (Scheme 2),
were examined for the Strecker reactions using K4[Fe(CN)6] as
an eco‑friendly cyanide source, benzoyl chloride as a promoter,
and potassium hydroxide as a base in ethanol.
N‑Benzyloxycarbonylaminobenzyl phenylsulfones containing
electron‑donating groups (MeO and Me) or electron‑
withdrawing substituents (F, Cl and Br) on aromatic rings of
R were successfully converted into the corresponding α‑amino
nitriles in high yield (Table 3, entries 2–13). This indicated that
the electronic effect of the substituents had little impact on the
reaction yield. On the other hand, N‑benzyloxycarbonylamino
phenylsulfone bearing a furan heterocycle underwent reaction
to form the corresponding product in only moderate yield
5
4e
4
78
O
6
7
CH3CH2
(CH3)2CH
4f
4g
3.5
3.5
80
81
aReaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2.4 mmol),
N‑tosylaminobenzyl phenylsulfones 3a–g (2.0 mmol) and potassium
hydroxide (3.0 mmol) in EtOH (10 mL) were stirred at room temperature.
bIsolated yields.
(Table 3, entry 14). Unfortunately an attempt of a similar
reaction with N‑benzyloxycarbonylaminobenzyl phenylsulfone
with an NO2 group on the aromatic ring of R was not successful,
and unidentified by‑products were observed.
The cyanation of N‑tosylaminobenzyl phenylsulfones was
also examined under similar conditions using K4[Fe(CN)6]
as an eco‑friendly cyanide source (Table 4). N‑tosylamino‑x‑
benzyl phenylsulfones gave high yields (entries 1–4). Other
analogues containing a furyl or an alkyl group (entries 5–7)
gave good yields.
A plausible mechanism for the Strecker reactions of
N‑benzyloxycarbonylaminobenzyl
phenylsulfones
with
PhO2S
R
O
O
CN O
O
(i) PhCOCl/160 oC/3 h
(ii) KOH-EtOH/rt
S
S
K4[Fe(CN)6]
+
N
H
N
H
R
3a-g
4a-g
Scheme 2 Cyanation of N‑tosylaminobenzyl phenylsulfones.
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434 JOURNAL OF CHEMICAL RESEARCH 2014
O
OH-
H2O,
Ph
Cl
O
CN-
Ph
CN
O
K4[Fe(CN)6]
KCl, FeCl2
O
O-
Ph
Ph
SO2
O
OH-
N
H
O
N
O
R
R
-
1
PhSO2 H O
,
A
2
O
CN
O
CN
H2O
N
N
O
O
R
R
H
2
OH-
B
Scheme 3 The proposed mechanism for the cyanation of N‑benzyloxycarbonylaminobenzyl phenylsulfones with K4[Fe(CN)6].
Benzyl cyano(phenyl)methylcarbamate (2a): White solid; m.p.
102–104 °C (EtOAc); IR (KBr, νmax): 3277 (NH), 1696 (C=O) cm–1;
1H NMR: δ 5.21 (s, 2H, CH2), 5.51 (bs, 1H, NH), 5.88 (d, J= 8.4 H z,
1H, CH), 7.40–7.51 (m, 10H, ArH) ppm; 13C NMR: δ 46.52, 67.91,
117.37, 126.89, 128.87, 128.50, 128.60, 129.35, 129.65, 132.94, 135.37,
154.96 ppm. Anal. calcd for C16H14N2O2: C, 72.17; H, 5.30; N, 10.52;
found: C, 72.05; H, 5.28; N, 10.49%.
Benzyl cyano(o‑tolyl)methylcarbamate (2b): White solid; m.p.
102–103 °C (EtOAc); IR (KBr, νmax): 3310 (NH), 1688 (C=O) cm–1;
1H NMR: δ 2.36 (s, 3H, CH3), 5.17 (s, 2H, CH2), 5.25 (d, J= 7.4 H z,
1H, NH), 5.91 (d, J=7.4 Hz, 1H, CH), 7.23–7.35 (m, 8H, ArH), 7.58
(d, J=7.6 Hz, 1H, ArH) ppm; 13C NMR: δ 18.78, 44.59, 67.86, 117.65,
126.92, 127.43, 128.24, 128.48, 128.60, 129.94, 130.87, 131.41, 135.40,
136.16, 154.71 ppm. Anal. calcd for C17H16N2O2: C, 72.84; H, 5.75; N,
9.99; found: C, 72.96; H, 5.77; N, 10.01%.
K4[Fe(CN)6] to synthesise N‑benzyloxycarbonyl α‑aminobenzyl
nitriles is shown in Scheme 3. K4[Fe(CN)6] first reacts with
benzoyl chloride to form benzoyl cyanide as an intermediate,
which can be isolated and identified.28 Then benzoyl
cyanide is attacked by water from undried solvent in the
presence of hydroxyl ion to produce cyanide ion in situ.
N‑Benzyloxycarbonylaminobenzyl phenylsulfones 1 transform
into N‑benzyloxycarbonyl imines A in the presence of
potassium hydroxide by elimination of benzensulfinate. Then
the intermediate A undergoes nucleophilic addition by CN– to
give intermediates B, which combine with hydrogen ions from
water to give the corresponding addition products 2.
Experimental
Benzyl cyano(p‑tolyl)methylcarbamate (2c): White solid; m.p.
106–108 °C (EtOAc); IR (KBr, νmax): 3282 (NH), 2253 (CN), 1670
(C=O) cm–1; 1H NMR: δ 2.29 (s, 3H, CH3), 5.08 (s, 2H, CH2), 5.29 (bs,
1H, NH), 5.71 (d, J=8.4 Hz, 1H, CH), 7.16 (d, J=8.4 Hz, 2H, ArH),
7.24–7.28 (m, 7H, ArH) ppm; 13C NMR: δ 21.13, 46.33, 67.85, 117.53,
126.83, 128.28, 128.49, 128.61, 129.99, 135.42, 139.77, 154.94 ppm.
Anal. calcd for C17H16N2O2: C, 72.84; H, 5.75; N, 9.99; found: C, 72.76;
H, 5.73; N, 9.95%.
IR spectra were recorded using KBr pellets on an Alpha Centauri
FTIR spectrophotometer. NMR spectra were obtained on a Mercury‑
400BB spectrometer (1H NMR at 400 Hz, 13C NMR at 100 Hz) in
CDCl3 using TMS as internal standard. Chemical shifts (δ) are given
in ppm and coupling constants (J) in Hz. Elemental analyses were
performed on a Vario El Elemental Analysis instrument. Melting
points were determined in an electrothermal melting point apparatus.
Potassium hexacyanoferrate(II) was dried at 80°C under vacuum for
24 h and finely powdered prior to use. N‑Benzyloxycarbonylamino‑
and N‑tosylamino‑benzyl phenylsulfones were prepared according to
literature procedures.29,30
Benzyl cyano(p‑methoxyphenyl)methylcarbamate (2d): White solid;
m.p. 105–106 °C (EtOAc); IR (KBr, νmax): 3297 (NH), 2243 (CN),
1
1689 (C=O) cm–1; H NMR: δ 3.73 (s, 3H, CH3), 5.08 (s, 2H, CH2),
5.30 (bs, 1H, NH), 5.68 (d, J=8.0 Hz, 1H, CH), 6.83–6.86 (m, 2H,
ArH), 7.27–7.32 (m, 7H, ArH) ppm; 13C NMR: δ 46.05, 55.37, 67.83,
114.64, 117.61, 124.92, 128.27, 128.35, 128.47, 128.60, 135.42, 154.90,
160.45 ppm. Anal. calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45;
found: C, 68.83; H, 5.43; N, 9.48%.
Cyanation of N‑benzyloxycarbonylamino‑ and N‑tosylamino‑benzyl
phenylsulfones to synthesise N‑benzyloxycarbonyl and N‑tosyl
α‑aminobenzyl nitriles; general procedure
A mixture of K4[Fe(CN)6] (0.4 mmol) and benzoyl chloride (2.4 mmol)
was heated at 160 °C for 3 h, then the reaction system was cooled to
room temperature. N‑Benzyloxycarbonylamino‑ or N‑tosylamino‑
benzyl phenylsulfones (2.0 mmol) and potassium hydroxide
(3.0 mmol) in 10 mL of ethanol were then added. The resulting
mixture was further stirred at room temperature for an appropriate
time which is indicated in Tables 3 and 4. The progress of the reaction
was monitored by TLC. After the completion of reaction, the reaction
mixture was concentrated and the residue was subject to silica gel flash
column chromatography using petroleum ether and ethyl acetate as
eluent to obtain the pure products. The analytical data of all products
are given below.
Benzyl cyano(3‑methoxyphenyl)methylcarbamate (2e): White solid;
m.p. 72–74 °C (EtOAc); IR (KBr, νmax): 3313 (NH), 2250 (CN), 1703
(C=O) cm–1; 1H NMR: δ 3.79 (s, 3H, CH3), 5.15 (s, 2H, CH2), 5.61 (bs,
1H, NH), 5.79 (d, J=7.6 Hz, CH), 6.91–7.05 (m, 3H, ArH), 7.29–7.34
(m, 6H, ArH) ppm; 13C NMR: δ 46.42, 55.33, 67.85, 112.47, 115.12,
117.34, 118.93, 128.21, 128.42, 128.55, 130.40, 134.42, 135.42, 155.05,
160.14 ppm. Anal. calcd for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45;
found: C, 68.87; H, 5.45; N, 9.43%.
Benzyl cyano(2‑methoxyphenyl)methylcarbamate (2f): White solid;
m.p. 92–94 °C (EtOAc); IR (KBr, νmax): 3316 (NH), 2248 (CN), 1712
(C=O) cm–1; 1H NMR: δ 3.91 (s, 3H, CH3), 5.14 (s, 2H, CH2), 5.85 (m,
2H, NH, CH), 6.95–7.00 (m, 2H, ArH), 7.34–7.42 (m, 7H, ArH) ppm;
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JOURNAL OF CHEMICAL RESEARCH 2014 435
13C NMR: δ 43.53, 55.78, 67.69, 111.48, 117.63, 121.12, 121.60, 128.31,
128.41, 128.57, 129.13, 131.32, 135.63, 154.94, 156.99 ppm. Anal. calcd
for C17H16N2O3: C, 68.91; H, 5.44; N, 9.45; found: C, 68.78; H, 5.46; N,
9.42%.
(m, 8H, ArH), 7.82 (t, J=8.4 Hz, 2H, ArH) ppm; 13C NMR: δ 21.62,
48.16, 116.19, 127.01, 127.28, 129.36, 129.87, 130.02, 131.99, 135.91,
144.70 ppm. Anal. calcd for C15H14N2O2S: C, 62.92; H, 4.93; N, 9.78;
found: C, 62.84; H, 4.92; N, 9.81%.
Benzyl benzo[d][1,3]dioxol‑5‑yl(cyano)methylcarbamate (2g): White
solid; m.p. 94–96 °C (EtOAc); IR (KBr, νmax): 3320 (NH), 2275 (CN),
1703 (C=O) cm–1; 1H NMR: δ 5.16 (s, 2H, CH2), 5.38 (d, J=8.0 Hz, 1H,
NH), 5.73 (d, J=8.0 Hz, 1H, CH), 5.99 (s, 2H, CH2), 6.81–6.97 (m, 4H,
ArH), 7.32–7.36 (m, 4H, ArH) ppm; 13C NMR: δ 46.28, 67.91, 101.70,
107.35, 108.71, 117.42, 120.80, 126.64, 128.29, 128.52, 128.62, 135.38,
148.50, 148.72, 154.88 ppm. Anal. calcd for C17H14N2O4: C, 65.80; H,
4.55; N, 9.03; found: C, 65.71; H, 4.56; N, 9.00%.
Benzyl cyano(4‑fluorophenyl)methylcarbamate (2h): White solid;
m.p. 93–94 °C (EtOAc); IR (KBr, νmax): 3281 (NH), 2251 (CN), 1684
(C=O) cm–1; 1H NMR: δ 5.16 (s, 2H, CH2), 5.60 (bs, 1H, NH), 5.82 (d,
J=8.0 Hz, 1H, CH), 7.09–7.17 (m, 2H, ArH), 7.36–7.46 (m, 7H, ArH)
ppm; 13C NMR: δ 45.79, 67.93, 116.24, 116.46, 117.21, 128.26, 128.52,
128.59, 128.85, 128.93, 135.24, 154.96, 161.91, 164.39 ppm. Anal. calcd
for C16H13FN2O2: C, 67.60; H, 4.61; N, 9.85; found: C,67.75; H, 4.60; N,
9.82%.
Benzyl cyano(2‑fluorophenyl)methylcarbamate (2i): White solid;
m.p. 102–103 °C (EtOAc); IR (KBr, νmax): 3316 (NH), 1684 (C=O) cm–1;
1H NMR: δ 5.17 (s, 2H, CH2), 5.57 (bs, 1H, NH), 5.98 (d, J=8.8 Hz,
1H, CH), 7.15–7.25 (m, 2H, ArH), 7.37–7.55 (m, 7H, ArH) ppm; 13C
NMR: δ 41.75, 67.94, 116.26, 116.46, 116.60, 120.80, 124.91, 124.95,
128.27, 128.49, 128.59, 129.12, 131.90, 131.97, 135.31, 154.68, 158.90,
161.39 ppm. Anal. calcd for C16H13FN2O2: C, 67.60; H, 4.61; N, 9.85;
found: C, 67.54; H, 4.63; N, 9.88%.
N‑(Cyano(4‑tolyl)methyl)‑4‑methylbenzenesulfonamide (4b): White
solid; m.p. 149–150 °C (EtOAc); IR (KBr, νmax): 3270 (NH), 2248 (NH),
1336 (S=O asym), 1160 (S=O sym) cm–1; 1H NMR (CDCl3, 400 MHz):
δ 2.28 (s, 3H, CH3), 2.38 (s, 3H, CH3), 5.08 (d, J=8.4 Hz, 1H, NH), 5.34
(d, J=8.4 Hz, 1H, CH), 7.12 (d, J=8.0 Hz, 2H, ArH), 7.23 (d, J=8.0 Hz,
2H, ArH), 7.28 (d, J=8.0 Hz, 2H, ArH), 7.72 (d, J=8.0 Hz, 2H, ArH)
ppm; 13C NMR (CDCl3, 100 MHz): δ 21.12, 21.62, 47.94, 116.42, 126.96,
127.30, 129.14, 129.98, 136.05, 139.99, 144.58 ppm. Anal. calcd for
C16H16N2O2S: C, 63.98; H, 5.37; N, 9.33; found: C, 64.10; H, 5.39; N,
9.30%.
N‑(4‑Chlorophenyl(cyano)methyl)‑4‑methylbenzenesulfonamide
(4c): White solid; m.p. 130–132 °C (EtOAc); IR (KBr, νmax): 3262 (NH),
2249 (CN), 1342 (S=O asym), 1160 (S=O sym) cm–1; 1H NMR: δ 2.46
(s, 3H, CH3), 5.30 (d, J=9.2 Hz, 1H, NH), 5.45 (d, J=9.2 Hz, 1H, CH),
7.35–7.39 (m, 6H, ArH), 7.77 (d, J=8.4 Hz, 2H, ArH) ppm; 13C NMR:
δ 21.60, 47.54, 115.96, 127.20, 128.46, 129.47, 130.03, 130.62, 135.78,
135.95, 144.80 ppm. Anal. calcd for C15H13ClN2O2S: C, 56.16; H, 4.08;
N, 8.73; found: C, 56.09; H, 4.10; N, 8.75%.
N‑(Cyano(2,4‑dichlorophenyl)methyl)‑4‑methylbenzenesulfonamide
(4d): White solid; m.p. 136–137 °C (EtOAc); IR (KBr, νmax): 3248
(NH), 2248 (CN), 1343 (S=O asym), 1158 (S=O sym) cm–1; 1H NMR:
δ 2.44 (s, 3H, CH3), 5.51 (s, 1H, NH), 5.63 (d, J=8.8 Hz, 1H, CH),
7.28–7.32 (m, 3H, ArH), 7.37 (s, 1H, ArH), 7.44 (d, J=8.4 Hz, 1H, ArH),
7.72 (d, J=8.0 Hz, 2H, ArH) ppm; 13C NMR: δ 21.70, 45.71, 115.53,
127.30, 128.09, 128.42, 129.97, 130.34, 130.44, 133.90, 135.73, 137.02,
144.84 ppm. Anal. calcd for C15H12Cl2N2O2S: C, 50.72; H, 3.41; N, 7.89;
found: C, 50.81; H, 3.40; N, 7.91%.
N‑(Cyano(furan‑2‑yl)methyl)‑4‑methylbenzenesulfonamide (4e):
White solid; m.p. 98–100 °C (EtOAc); IR (KBr, νmax): 3277 (NH),
2251 (CN), 1337 (S=O asym), 1161 (S=O sym) cm–1; 1H NMR: δ 2.44
(s, 3H, CH3), 5.37 (d, J=9.2 Hz, 1H, NH), 5.53 (d, J=9.2 Hz, 1H,
CH), 6.34–6.35 (m, 1H, Fu‑H), 6.47 (d, J=3.6 Hz, 1H, Fu‑H), 7.34 (d,
J=8.4 Hz, 2H, ArH), 7.38 (s, 1H, Fu‑H), 7.77 (d, J=8.4 Hz, 2H, ArH)
ppm; 13C NMR: δ 21.85, 42.44, 110.55, 111.04, 114.71, 127.29, 131.22,
135.90, 143.90, 144.48, 144.82 ppm. Anal. calcd for C13H12N2O3S: C,
56.51; H, 4.38; N, 10.14; found: C, 56.43; H, 4.37; N, 10.11%.
N‑(1‑Cyanopropyl)‑4‑methylbenzenesulfonamide (4f): White solid;
m.p. 52–54 °C (EtOAc); IR (KBr, νmax): 3283 (NH), 2249 (CN), 1333
(S=O asym), 1161 (S=O sym) cm–1; 1H NMR: δ 0.95–0.96 (m, 3H, CH3),
2.01–2.04 (m, 2H, CH2), 2.44 (s, 3H, CH3), 4.69 (d, J=9.2 Hz, 1H, CH),
5.12 (bs, 1H, NH), 7.26–7.36 (m, 2H, ArH), 7.77–7.79 (m, 2H, ArH)
ppm; 13C NMR: δ 13.25, 21.28, 21.60, 51.16, 116.00, 126.03, 127.25,
129.94, 134.24, 136.15, 144.49 ppm. Anal. calcd for C11H14N2O2S: C,
55.44; H, 5.92; N, 11.76; found: C, 55.56; H, 5.90; N, 11.73%.
N‑(1‑Cyano‑2‑methylpropyl)‑4‑methylbenzenesulfonamide (4g):
White solid; m.p. 78–79 °C (EtOAc); IR (KBr, νmax): 3281 (NH),
2240 (CN), 1339 (S=O asym), 1162 (S=O sym) cm–1; 1H NMR: δ 1.04
(d, J=6.8 Hz, 6H, CH3), 1.99–2.07 (m, 1H, CH), 2.44 (s, 3H, CH3),
4.01–4.05 (m, 1H, CH), 5.53 (bs, 1H, NH), 7.35 (d, J=7.6 Hz, 2H, ArH),
7.78 (d, J=7.6 Hz, 2H, ArH) ppm; 13C NMR: δ 17.80, 18.48, 21.69,
32.38, 50.61, 116.75, 127.23, 130.08, 135.96, 144.56 ppm. Anal. calcd
for C12H16N2O2S: C, 57.12; H, 6.39; N, 11.10; found: C, 57.05; H, 6.41; N,
11.07%.
Benzyl cyano(2‑chlorophenyl)methylcarbamate (2j): White solid; m.p.
1
112–114 °C (EtOAc); IR (KBr, νmax): 3313 (NH), 1701 (C=O) cm–1; H
NMR: δ 4.89 (s, 2H, CH2), 5.32 (bs, 1H, NH), 5.80 (d, J=8.4 Hz, 1H, CH),
7.05–7.21 (m, 8H, ArH), 7.36 (d, J=7.6 Hz, 1H, ArH) ppm; 13C NMR:
δ 44.79, 67.91, 116.69, 127.66, 128.25, 128.47, 128.58, 129.45, 130.54,
130.63, 131.24, 133.29, 135.35, 154.67 ppm. Anal. calcd for C16H13ClN2O2:
C, 63.90; H, 4.36; N, 9.31; found: C, 63.85; H, 4.35; N, 9.28%.
Benzyl cyano(4‑chlorophenyl)methylcarbamate (2k): White solid;
m.p. 98–99 °C (EtOAc); IR (KBr, νmax): 3319 (NH), 1699 (C=O) cm–1;
1H NMR: δ 5.17 (s, 2H, CH2), 5.40 (bs, 1H, NH), 5.84 (d, J= 8.4 H z,
1H, CH), 7.36–7.43 (m, 9H, ArH) ppm; 13C NMR: δ 45.94, 68.09,
116.98, 128.28, 128.34, 128.61, 128.66, 129.59, 131.53, 135.26, 135.83,
154.92 ppm. Anal. calcd for C16H13ClN2O2: C, 63.90; H, 4.36; N, 9.31;
found: C, 63.99; H, 4.38; N, 9.34%.
Benzyl cyano(2,4‑dichlorophenyl)methylcarbamate (2l): White
solid; m.p. 92–93 °C (EtOAc); IR (KBr, νmax): 3290 (NH), 2249 (CN),
1697 (C=O) cm–1; 1H NMR: δ 4.76 (s, 2H, CH2), 5.40 (bs, 1H, NH), 5.63
(d, J=8.0 Hz, 1H, CH), 6.90–7.08 (m, 7H, ArH), 7.19 (d, J=8.0 Hz, 1H,
ArH) ppm; 13C NMR: δ 44.37, 68.16, 116.54, 128.06, 128.41, 128.68,
128.76, 129.46, 130.42, 134.19, 135.39, 136.77, 154.96 ppm. Anal. calcd
for C16H12Cl2N2O2: C, 57.33; H, 3.61; N, 8.36; found: C,57.41; H, 3.60; N,
8.33%.
Benzyl cyano(4‑bromophenyl)methylcarbamate (2m): White solid;
m.p. 102–104 °C (EtOAc); IR (KBr, νmax): 3321 (NH), 1698 (C=O) cm–1;
1H NMR: δ 5.09 (s, 2H, CH2), 5.34 (bs, 1H, NH), 5.74 (d, J=8.4 Hz, 1H,
CH), 7.18–7.32 (m, 7H, ArH), 7.48 (d, J=8.4 Hz, 1H, ArH) ppm; 13C
NMR: δ 45.99, 68.10, 116.92, 123.97, 128.34, 128.53, 128.61, 128.66,
132.07, 132.54, 135.24, 154.92 ppm. Anal. calcd for C16H13BrN2O2: C,
55.67; H, 3.80; N, 8.12; found: C, 55.79; H, 3.79; N, 8.09%.
Benzyl cyano(furan‑2‑yl)methylcarbamate (2n): White solid; m.p.
78–80 °C (EtOAc); IR (KBr, νmax): 3296 (NH), 2268 (CN), 1691 (C=O)
cm–1; 1H NMR: δ 5.08 (s, 2H, CH2), 5.56 (d, J=8.0 Hz, 1H, NH), 5.95 (d,
J=9.6 Hz, 1H, CH), 6.25–6.27 (m, 2H, Fu‑H), 7.18–7.29 (m, 6H, ArH,
The authors thank the National Natural Science Foundation of
China (21162024) and Key Laboratory of Eco‑Environment‑
Related Polymer Materials for Ministry of Education for the
financial support of this work.
1
Fu‑H) ppm; H NMR: δ 58.42, 67.19, 107.26, 110.24, 128.14, 128.27,
128.55, 136.03, 142.58, 151.26 ppm. Anal. calcd for C14H12N2O3: C,
65.62; H, 4.72; N, 10.93; found: C, 65.57; H, 4.70; N, 10.89%.
N‑(Cyanophenylmethyl)‑4‑methylbenzenesulfonamide (4a): White
solid; m.p. 152–154 °C (EtOAc); IR (KBr, νmax): 3254 (NH), 2245 (CN),
1334 (S=O asym), 1157 (S=O sym) cm–1; 1H NMR: δ 2.46 (s, 3H, CH3),
5.10 (d, J=8.4 Hz, 1H, NH), 5.48 (d, J=8.4 Hz, 1H, CH), 7.36–7.46
Received 23 April 2014; accepted 29 May 2014
Paper 1402609 doi: 10.3184/174751914X14030207593683
Published online: 12 July 2014
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