Synthesis of N -sulfonylamidines by catalyst-free hydroamination of ynamides and amines

Article abstract of DOI:10.1055/s-0033-1340287

A novel synthesis of N-sulfonylamidines by catalyst-free hydroamination of N,N-disulfonyl ynamides with amines was developed. Alkyl amines react with N,N-disulfonyl ynamides under mild conditions, whereas aryl amines require higher temperatures. Plausible mechanisms are proposed to explain this reaction.

Full text of DOI:10.1055/s-0033-1340287

PAPER
▌183
paper
Synthesis of N-Sulfonylamidines by Catalyst-Free Hydroamination of
Ynamides and Amines
Synthesis of N-Sulfonylamidines
Yulong Kong, Lian Yu, Yuming Cui, Jian Cao*
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University,
Wenyi Road 222, Hangzhou 310012, P. R. of China
Fax +86(571)28865135; E-mail: caojian@hznu.edu.cn
Received: 25.09.2013; Accepted after revision: 28.10.2013
actions: 0.5 mmol of 1 and 2.0 mmol of 2 in dichlorometh-
ane at room temperature for four hours with stirring.
Abstract: A novel synthesis of N-sulfonylamidines by catalyst-free
hydroamination of N,N-disulfonyl ynamides with amines was de-
veloped. Alkyl amines react with N,N-disulfonyl ynamides under
mild conditions, whereas aryl amines require higher temperatures.
Plausible mechanisms are proposed to explain this reaction.
a. gold(I)-catalyzed hydroamination of ynamides with anilines
R3
R3
N
R4
Au cat.
N
R1
N
+
Key words: amines, sulfonamides, aminations
R1
R4
R2
NH2
R2
b. this work: catalyst-free hydroamination of ynamides
SO2Ph
The amidine group is a fundamental motif of various bio-
active natural products,1 and amidines can serve as effi-
cient coordinating ligands and important synthetic
intermediates.2 Although many methods have been estab-
lished for the synthesis of amidines,3 more-efficient strat-
egies are still needed. The intermolecular hydroamination
of alkynes is an efficient method for preparing substituted
amines and imines or ketones.4,5 Ynamides, an important
subclass of alkynes, have emerged as important synthons
in modern organic synthesis,6–8 and a variety of synthetic
targets, including amidines,8a have been constructed from
ynamides. Recently, Skrydstrup and co-workers devel-
oped an elegant synthesis of amidines by gold(I)-cata-
lyzed hydroamination of ynamides with anilines (Scheme
1, a).9 However, there are few reports on catalyst-free hy-
droaminations of ynamides.10 In the course of a study on
hydroamination reactions of ynamides, we found that
N,N-disulfonyl ynamides11 react spontaneously with
amines without any catalyst (Scheme 1, b). Here, we re-
port this novel catalyst-free hydroamination reaction of
ynamides that provides ready access to N-sulfonylami-
dines.
SO2Ph
R2
N
CH2Cl2
N
+
R1
R2
N
R3
HN
SO2Ph
r.t.
R3
R1
Scheme 1 Synthesis of amidines from ynamides
Table 1 Optimization of the Reaction Conditions
SO2Ph
SO2Ph
N
CH2Cl2
N
+ BnNH2
Ph
Bn
SO2Ph
r.t.
N
2a
H
Ph
1a
3a
Entrya
Solvent
Ratio 1a/2a
Yield (%) of 3a
1
2
3
4
5
6
7
CH2Cl2
CH2Cl2
CH2Cl2
THF
1:1
1:2
1:4
1:4
1:4
1:4
1:4
27
55
89
44
70
64
76
MeCN
toluene
DMF
We began our studies by examining the reaction of equi-
molar ratios of ynamide 1a and benzylamine (2a) in di-
chloromethane at room temperature. The expected N-
sulfonylamidine 3a was obtained in 27% yield in the ab-
sence of a catalyst (Table 1, entry 1). Increasing the quan-
tity of amine 2a to four equivalents significantly improved
the yield of 3a to 89% (entries 2 and 3). Subsequent
screening of solvents showed that dichloromethane gave
the best results, and that the use of other common sol-
vents, such as toluene or tetrahydrofuran, did not improve
the yield (entries 4–7). We therefore chose the following
conditions as optimized conditions for all subsequent re-
a Unless otherwise specified, the reaction was carried out by using 1a
(0.5 mmol) and 2a (0.5–2.0 mmol) in solvent (4 mL) at r.t. for 4 h.
By using these optimized conditions, we examined the
scope of this catalyst-free hydroamination reaction. The
reaction was successful for various N,N-disulfonyl yn-
amides 1. The R1 group of ynamide 1 can be a phenyl
group optionally substituted with either an electron-do-
nating or an electron-withdrawing group (Table 2, entries
1–5). A variety of amines, including primary, secondary,
acyclic, and cyclic amines, were all efficiently coupled to
give the corresponding N-sulfonylamidines (entries 1 and
5–8). The reaction was also successful when bulky tert-
butylamine (2e) was used, albeit with a low yield (entry
SYNTHESIS 2014, 46, 0183–0188
Advanced online publication: 22.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340287; Art ID: SS-2013-H0644-OP
© Georg Thieme Verlag Stuttgart · New York

184
Y. Kong et al.
PAPER
9). However, the presence of a free hydroxy group was not 100 °C in 1,4-dioxane for 24 hours; in these cases, the
tolerated in this reaction (entry 10). starting material was recovered (Scheme 3).
Aryl amines did not undergo the hydroamination reaction In every case where reaction did occur, the sulfonamide
under these mild conditions. However, under modified PhSO2NR2R3 was obtained as a byproduct; we therefore
conditions (1,4-dioxane solvent, 100 °C), anilines 2g–i suggest the mechanism shown in Scheme 4. Ynamide 1
also reacted smoothly with ynamides 1a to give the corre- and amine 2 undergoes a spontaneous hydroamination re-
sponding amidines 3j–l (Scheme 2).
action to form intermediate A, which is desulfonylated by
a second molecule of amine 2 to give the N-sulfonylami-
dine product 3 (route a). Another elimination–addition
Note, however, that N-monosulfonyl ynamides 1f and 1g
did not undergo this hydroamination reaction, even at
Table 2 Synthesis of N-Sulfonylamidines 3a
SO2Ph
SO2Ph
R2
N
CH2Cl2
r.t.
N
+
R1
R2
HN
SO2Ph
N
R3
R1
R3
2
1
3
Entry
Ynamide (R1)
Amine
Product
Yield (%)
89
SO2Ph
NHBn
N
1
2
1a
1b
Ph
2a
BnNH2
BnNH2
3a
Ph
Cl
SO2Ph
NHBn
N
4-ClC6H4
4-PrC6H4
2a
2b
3b
3c
65
92
n-Pr
MeO
F
SO2Ph
N
n-Pr
3
4
5
6
1c
1d
1e
1a
Pr2NH
Pr2NH
Pr2NH
N
n-Pr
SO2Ph
N
n-Pr
4-MeOC6H4
4-FC6H4
Ph
2b
2b
2c
3d
3e
3f
88
95
65
N
n-Pr
SO2Ph
N
n-Pr
N
n-Pr
SO2Ph
N
N
N
Ph
Ph
N
H
SO2Ph
N
O
7
8
1a
1a
Ph
Ph
2d
2b
3g
58
66
N
H
O
SO2Ph
N
N
Ph
Ph
n-Pr
Pr2NH
3h
3i
N
n-Pr
SO2Ph
9b
1a
1a
Ph
Ph
2e
2f
t-BuNH2
22
–
t-Bu
N
H
Me
N
OH
10
unidentified mixture
H
a Unless otherwise specified, the reaction was carried out by using 1 (0.5 mmol) and 2 (2.0 mmol) in CH2Cl2 (4 mL) at r.t. for 4 h.
b The reaction time was 24 h.
Synthesis 2014, 46, 183–188
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of N-Sulfonylamidines
185
Ynamides were prepared by Muñiz’s method.11 The properties of
previously unreported ynamides are listed below.
SO2Ph
SO2Ph
N
N
Me
Ph
Et3N
+
Ph
Me
N
HN
SO2Ph
1,4-dioxane
100 °C
N-[(4-Chlorophenyl)ethynyl]-N-(phenylsulfonyl)benzenesul-
fonamide (1b)
Pale-yellow solid; yield: 526.9 mg (61%); mp 139–141 °C
(CH2Cl2).
IR (KBr): 3065, 2237, 1448, 1371, 1170, 1083, 823 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.0 Hz, 4 H), 7.69–
7.74 (m, 2 H), 7.56–7.60 (m, 4 H), 7.29–7.37 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 137.7, 135.1, 135.0, 133.3, 129.4,
Ph
Ph
3j 69%
12 h
1a
2g
SO2Ph
N
N
SO2Ph
N
Ph
Et3N
+
SO2Ph
1,4-dioxane
100 °C
12 h
N
H
Ph
1a
2h
128.8, 128.6, 120.1, 77.0, 76.3.
HRMS (ESI): m/z [M + Na]+ calcd for C20H14ClNNaO4S2:
453.9945; found: 453.9946.
3k 54%
SO2Ph
SO2Ph
N
N
Et3N
+ PhNH2
Ph
Ph
N-(Phenylsulfonyl)-N-[(4-propylphenyl)ethynyl]benzenesul-
fonamide (1c)
Brown oil; yield: 606.5 mg (69%).
SO2Ph
N
1,4-dioxane
100 °C
2i
H
Ph
1a
12 h
3l 87%
IR (neat): 2927, 2239, 1393, 1173, 1083, 841, 681 cm–1.
Scheme 2 Synthesis of amidines from aryl amines
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.0 Hz, 4 H), 7.71–
7.73 (m, 2 H), 7.57–7.59 (m, 4 H), 7. 36 (d, J = 8.0 Hz, 2 H), 7.15
(d, J = 8.0 Hz, 2 H), 2.59 (t, J = 8.0 Hz, 2 H), 1.60–1.67 (m, 2 H),
0.94 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 144.2, 137.9, 134.8, 132.3, 129.2,
128.61, 128.58, 118.7, 78.2, 74.7, 38.0, 24.3, 13.8.
R
SO2Ph
SO2Ph
N
n-Pr
CH2Cl2, r.t.
N
R
+
NH
Ph
n-Pr
X
N
or
n-Pr
1,4-dioxane
100 °C
Ph
HRMS (ESI): m/z [M + Na]+ calcd for C23H21NNaO4S2: 462.0804;
found: 462.0810.
n-Pr
1f R = Bn
1g R = Ph
2b
0%
24 h
N-[(4-Methoxyphenyl)ethynyl]-N-(phenylsulfonyl)benzenesul-
fonamide (1d)
Scheme 3 Attempted reaction with N-monosulfonyl ynamides
Pale-yellow solid; yield: 607.0 mg (71%); mp 119–121 °C
(CH2Cl2).
IR (KBr): 2935, 1604, 1569, 1392, 1264, 1173, 732 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.0 Hz, 4 H), 7.71–
7.72 (m, 2 H), 7.57–7.59 (m, 4 H), 7.38 (d, J = 8.0 Hz, 2 H), 6.85
(d, J = 8.0 Hz, 2 H), 3.82 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.4, 137.9, 134.7, 134.3, 129.2,
128.6, 114.0, 113.5, 78.1, 74.1, 55.4.
HRMS (ESI): m/z [M + Na]+ calcd for C21H17NNaO5S2: 450.0440;
found: 450.0438.
mechanism via the intermediate ketenimine B (route b)
cannot be ruled out. Neither A nor B was detected.
In conclusion, we have described a novel synthesis of N-
sulfonylamidines by a catalyst-free hydroamination of yn-
amides with amines. Alkyl amines react with N,N-disulfo-
nyl ynamides under very mild conditions, whereas aryl
amines require higher temperatures. Plausible mecha-
nisms are proposed to explain this reaction, and further in-
vestigations on the mechanistic details and applications of
this reaction are ongoing in our laboratory.
N-[(4-Fluorophenyl)ethynyl]-N-(phenylsulfonyl)benzenesul-
fonamide (1e)
Light-gray solid; yield: 481.9 mg (58%); mp 126–128 °C (CH2Cl2).
IR (KBr): 3066, 2241, 1449, 1392, 1175, 1083, 834 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.05–8.06 (m, 4 H), 7.71–7.75 (m,
2 H), 7.58–7.60 (m, 4 H), 7.41–7.43 (m, 2 H), 7.01–7.04 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.2, 161.8, 137.9, 134.9, 134.4,
134.3, 129.3, 128.6, 117.7, 115.9, 115.7, 75.0.
HRMS (ESI): m/z [M + Na]+ calcd for C20H14FNNaO4S2: 438.0240;
found: 438.0245.
All commercially available chemicals and reagents were used with-
out any further purification. Flash column chromatography was car-
ried out by using 300–400 mesh silica gel. 1H and 13C NMR spectra
were recorded at 400 and 100 MHz, respectively, on a Bruker
Avance 400 spectrometer with TMS as the internal standard and
CDCl3 as solvent. High-resolution mass spectra were recorded on a
Waters Micromass GCT mass spectrometer operating in the ESI-
TOF mode. IR spectra were recorded on a Bruker Vector 22 spec-
trophotometer.
SO2Ph
N
PhO2S
R1
SO2Ph
R22NSO2Ph
R22NH
N
a
SO2Ph
NR2
SO2Ph
2
R1
N
1
A
R1
+
NR2
2
R22NH
N
b
R1
•
SO2Ph
3
R22NH
2
R22NSO2Ph
B
Scheme 4 Proposed reaction mechanisms
© Georg Thieme Verlag Stuttgart · New York
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186
Y. Kong et al.
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N-Benzyl-2-phenyl-N′-(phenylsulfonyl)ethanimidamide (3a);
Typical Procedure
IR (neat): 2965, 1542, 1270, 1139, 1085, 834 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 6.4 Hz, 2 H), 7.34–
7.37 (m, 3 H), 7.05–7.15 (m, 2 H), 6.86–6.90 (m, 2 H), 4.30 (s, 2 H),
3.32 (t, J = 5.6 Hz, 2 H), 3.03 (t, J = 5.6 Hz, 2 H), 1.51–1.53 (m, 2
H), 1.28–1.30 (m, 2 H), 0.76 (t, J = 8.0 Hz, 3 H), 0.68 (t, J = 8.0 Hz,
3 H).
13C NMR (100 MHz, CDCl3): δ = 164.7, 162.3, 160.4, 144.1, 131.3,
130.20, 130.17, 129.64, 129.56, 128.4, 126.0, 115.8, 115.6, 50.8,
50.6, 36.0, 21.6, 20.0, 11.3, 11.0.
BuNH2 (2a; 2.0 mmol, 214.4 mg, 4.0 equiv) was added to a solution
of disulfonamide 1a (0.5 mmol, 198.8 mg) in CH2Cl2 (4 mL), and
the mixture was stirred at r.t. for 4 h until 1a was consumed [TLC,
hexane–EtOAc (6:1)]. The mixture was then concentrated and the
residue was purified by flash chromatography [silica gel, hexane–
EtOAc (6:1 to 4:1)] to give a pale-tan solid; yield: 162.4 mg (89%);
mp 99–101 °C (CH2Cl2).
IR (KBr): 2922, 1552, 1265, 1140, 1090, 731, 688 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C20H25FN2NaO2S: 399.1513;
found: 399.1522.
1H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.4 Hz, 2 H), 7.40–
7.51 (m, 3 H), 7.18–7.33 (m, 8 H), 7.04–7.06 (m, 2 H), 5.96 (br s, 1
H), 4.40 (d, J = 5.6 Hz, 2 H), 4.29 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 166.7, 143.4, 136.5, 133.1, 131.7,
130.0, 129.4, 128.7, 128.6, 128.1, 127.7, 127.6, 126.3, 45.9, 39.7.
N-(2-Phenyl-1-pyrrolidin-1-ylethylidene)benzenesulfonamide
(3f)
Pale-tan solid; yield: 106.6 mg (65%); mp 119–121 °C (CH2Cl2).
IR (KBr): 2977, 1539, 1195, 1136, 1086, 815, 727cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C21H20N2NaO2S: 387.1138;
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.0 Hz, 2 H), 7.36–
7.41 (m, 3 H), 7.13–7.24 (m, 5 H), 4.33 (s, 2 H), 3.54–3.60 (m, 2 H),
3.17–3.26 (m, 2 H), 1.75–1.83 (m, 4 H).
found: 387.1152.
N-Benzyl-2-(4-chlorophenyl)-N′-(phenylsulfonyl)ethanimid-
amide (3b)
Light-gray solid; yield: 130.4 mg (65%); mp 126–128 °C (CH2Cl2).
13C NMR (100 MHz, CDCl3): δ = 164.1, 144.2, 133.6, 131.3, 128.8,
128.5, 128.2, 126.8, 126.3, 49.0, 47.7, 38.3, 25.7, 24.0.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20N2NaO2S: 351.1138;
found: 351.1144.
IR (KBr): 2924, 1551, 1270, 1138, 1089, 733 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.0 Hz, 2 H), 7.38–
7.49 (m, 3 H), 7.22–7.25 (m, 5 H), 7.06–7.13 (m, 4 H), 6.12 (br s, 1
H), 4.40 (d, J = 5.2 Hz, 2 H), 4.21 (s, 2 H).
N-(1-Morpholino-2-phenylethylidene)benzenesulfonamide (3g)
Light-gray solid; yield: 99.8 mg (58%); mp 121–123 °C (CH2Cl2).
13C NMR (100 MHz, CDCl3): δ = 165.9, 143.2, 136.4, 133.9, 131.7,
IR (KBr): 2856, 1536, 1443, 1268, 1140, 1086, 720 cm–1.
131.1, 129.4, 128.7, 128.6, 127.8, 127.7, 126.2, 46.0, 38.9.
HRMS (ESI): m/z [M + Na]+ calcd for C21H19ClN2NaO2S:
421.0748; found: 421.0758.
1H NMR (400 MHz, CDCl3): δ = 7.92–7.93 (m, 2 H), 7.42–7.49 (m,
3 H), 7.21–7.30 (m, 3 H), 7.16 (d, J = 8.0 Hz, 2 H), 4.45 (s, 2 H),
3.79–3.80 (m, 2 H), 3.62–3.63 (m, 2 H), 3.32–3.34 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 165.1, 143.6, 134.0, 131.6, 129.1,
128.6, 127.9, 127.1, 126.4, 66.2, 66.1, 46.9, 45.0, 36.9.
N′-(Phenylsulfonyl)-N,N-dipropyl-2-(4-propylphenyl)ethan-
imidamide (3c)
Brown oil; yield: 185.2 mg (92%).
IR (neat): 2961, 1541, 1468, 1271, 1140, 1086, 727 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20N2NaO3S: 367.1087;
1H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 8.0 Hz, 2 H), 7.32–
7.40 (m, 3 H), 7.01 (m, 4 H), 4.31 (s, 2 H), 3.34 (t, J = 8.0 Hz, 2 H),
3.05 (t, J = 8.0 Hz, 2 H), 2.49 (t, J = 8.0 Hz, 2 H), 1.53–1.58 (m, 4
H), 1.26–1.30 (m, 2 H), 0.87 (t, J = 8.0 Hz, 3 H), 0.79 (t, J = 8.0 Hz,
3 H), 0.68 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.2, 144.3, 141.1, 131.5, 131.2,
128.9, 128.3, 127.8, 126.1, 50.8, 50.6, 37.5, 36.4, 24.5, 21.6, 20.0,
13.7, 11.4, 11.0.
found: 367.1086.
2-Phenyl-N′-(phenylsulfonyl)-N,N-dipropylethanimidamide
(3h)
Pale-yellow solid; yield: 118.1 mg (66%); mp 110–112 °C
(CH2Cl2).
IR (KBr): 2965, 1543, 1432, 1273, 1141, 1087, 727 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.86–7.88 (m, 2 H), 7.34–7.43 (m,
3 H), 7.17–7.25 (m, 3 H), 7.12 (d, J = 8.0 Hz, 2 H), 4.37 (s, 2 H),
3.37 (t, J = 7.6 Hz, 2 H), 3.06 (t, J = 7.6 Hz, 2 H), 1.55–1.59 (m, 2
H), 1.31–1.35 (m, 2 H), 0.81 (t, J = 7.6 Hz, 3 H), 0.71 (t, J = 7.6 Hz,
3 H).
13C NMR (100 MHz, CDCl3): δ = 164.9, 144.2, 134.4, 131.3, 128.9,
128.4, 127.9, 126.9, 126.1, 50.8, 50.6, 36.8, 21.6, 20.0, 11.4, 11.0.
HRMS (ESI): m/z [M + Na]+ calcd for C23H32N2NaO2S: 423.2077;
found: 423.2091.
2-(4-Methoxyphenyl)-N′-(phenylsulfonyl)-N,N-dipropylethan-
imidamide (3d)
Brown oil; yield: 170.6 mg (88%).
IR (neat): 2963, 1541, 1246, 1139, 1086, 833 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C20H26N2NaO2S: 381.1607;
1H NMR (400 MHz, CDCl3): δ = 7.84–7.86 (m, 2 H), 7.33–7.41 (m,
3 H), 7.03 (d, J = 8.0 Hz, 2 H), 6.75 (d, J = 8.0 Hz, 2 H), 4.27 (s, 2
H), 3.70 (s, 3 H), 3.33 (t, J = 8.0 Hz, 2 H), 3.06 (t, J = 8.0 Hz, 2 H),
1.50–1.57 (m, 2 H), 1.28–1.34 (m, 2 H), 0.78 (t, J = 8.0 Hz, 3 H),
0.70 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.3, 158.4, 144.2, 131.2, 129.0,
128.4, 126.3, 126.0, 114.2, 55.2, 50.8, 50.6, 36.0, 21.6, 20.0, 11.4,
11.1.
found: 381.1611.
N-(tert-Butyl)-2-phenyl-N′-(phenylsulfonyl)ethanimidamide
(3i)
Light-gray solid; yield: 36.3 mg (22%); mp 161–163 °C (CH2Cl2).
IR (KBr): 3309, 2917, 1546, 1273, 1138, 1088, 683 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.96–7.98 (m, 2 H), 7.45–7.52 (m,
3 H), 7.33–7.37 (m, 3 H), 7.20–7.22 (m, 2 H), 5.09 (br s, 1 H), 4.27
(s, 2 H), 1.22 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 165.1, 143.8, 133.5, 131.5, 130.0,
129.4, 128.6, 128.1, 126.1, 53.4, 40.6, 28.0.
HRMS (ESI): m/z [M + Na]+ calcd for C21H28N2NaO3S: 411.1713;
found: 411.1730.
HRMS (ESI): m/z [M + Na]+ calcd for C18H22N2NaO2S: 353.1294;
found: 353.1290.
2-(4-Fluorophenyl)-N′-(phenylsulfonyl)-N,N-dipropylethan-
imidamide (3e)
Brown oil; yield: 178.4 mg (95%).
Synthesis 2014, 46, 183–188
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of N-Sulfonylamidines
187
N-Methyl-N,2-diphenyl-N′-(phenylsulfonyl)ethanimidamide
(3j); Typical Procedure
(3) For recent examples, see: (a) Bae, I.; Han, H.; Chang, S.
J. Am. Chem. Soc. 2005, 127, 2038. (b) Kumagai, N.;
Matsunaga, S.; Shibasaki, M. Angew. Chem. Int. Ed. 2004,
43, 478. (c) Saluste, C. G.; Whitby, R. J.; Furber, M. Angew.
Chem. Int. Ed. 2000, 39, 4156. (d) Keung, W.; Bakir, F.;
Patron, A. P.; Rogers, D.; Priest, C. D.; Darmohusodo, V.
Tetrahedron Lett. 2004, 45, 733.
(4) For recent reviews, see: (a) Alonso, F.; Beletskaya, I. P.;
Yus, M. Chem. Rev. 2004, 6, 3079. (b) Severin, R.; Doye, S.
Chem. Soc. Rev. 2007, 36, 1407. (c) Müller, T. E.; Hultzsch,
K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108,
3795.
(5) For recent examples, see: (a) Bertrand, G.; Donnadieu, B.;
Kinjo, R.; Frey, G. D.; Zeng, X. J. Am. Chem. Soc. 2009,
131, 8690. (b) Zeng, X.; Frey, G. D.; Kousar, S.; Bertrand,
G. Chem. Eur. J. 2009, 15, 3056. (c) Shi, Z.; Zhang, C.; Li,
S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem. Int. Ed.
2009, 48, 4572. (d) Liu, C.-C.; Korivi, R. P.; Cheng, C.-H.
Chem. Eur. J. 2008, 14, 9503. (e) Lingaiah, N.; Babu, N. S.;
Reddy, K. M.; Prasad, P. S. S.; Suryanarayana, I. Chem.
Commun. 2007, 278.
(6) For recent reviews, see: (a) DeKorver, K. A.; Li, H.; Lohse,
A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem.
Rev. 2010, 110, 5064. (b) Evano, G.; Coste, A.; Jouvin, K.
Angew. Chem. Int. Ed. 2010, 49, 2840. (c) Evano, G.;
Jouvin, K.; Coste, A. Synthesis 2013, 45, 17.
(7) For syntheses of ynamides, see: (a) Frederick, M. O.;
Mulder, J. A.; Tracey, M. R.; Hsung, R. P.; Huang, J.; Kurtz,
K. C. M.; Shen, L.; Douglas, C. J. J. Am. Chem. Soc. 2003,
125, 2368. (b) Zhang, Y.; Hsung, R. P.; Tracey, M. R.;
Kurtz, K. C. M.; Vera, E. L. Org. Lett. 2004, 6, 1151.
(c) Zhang, X.; Zhang, Y.; Huang, J.; Hsung, R. P.; Kurtz, K.
C. M.; Oppenheimer, J.; Petersen, M. E.; Sagamanova, I. K.;
Shen, L.; Tracey, M. R. J. Org. Chem. 2006, 71, 4170.
(d) Coste, A.; Karthikeyan, G.; Couty, F.; Evano, G. Angew.
Chem. Int. Ed. 2009, 48, 4381. (e) Coste, A.; Couty, F.;
Evano, G. Org. Lett. 2009, 11, 4454. (f) Hamada, T.; Ye, X.;
Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 833. (g) Jia, W.;
Jiao, N. Org. Lett. 2010, 12, 2000. (h) Jouvin, K.; Couty, F.;
Evano, G. Org. Lett. 2010, 12, 3272. (i) Sueda, T.; Oshima,
A.; Teno, N. Org. Lett. 2011, 13, 3996. (j) Laouiti, A.;
Rammah, M. M.; Rammah, M. B.; Marrot, J.; Couty, F.;
Evano, G. Org. Lett. 2012, 14, 6. (k) Jouvin, K.;
PhNHMe (2g; 2.0 mmol, 214.4 mg, 4.0 equiv) was added to a solu-
tion of disulfonamide 1a (0.5 mmol, 198.8 mg) in 1,4-dioxane (4
mL) containing Et3N (0.5 mL), and the mixture was stirred at 100
°C for 12 h until 1a was consumed [TLC, hexane–EtOAc (6:1)].
The mixture was then concentrated, and the residue was purified by
flash chromatography [silica gel, hexane–EtOAc (6:1 to 4:1)] to
give a brown oil; yield: 126.5 mg (69%).
IR (neat): 3062, 1530, 1277, 1143, 1088, 690 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.0 Hz, 2 H), 7.45–
7.48 (m, 3 H), 7.19–7.26 (m, 3 H), 7.06 (d, J = 4.0 Hz, 3 H), 6.77–
6.79 (m, 4 H), 4.24 (s, 2 H), 3.32 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.6, 143.9, 142.5, 134.6, 131.6,
129.6, 128.6, 128.5, 128.4, 128.3, 127.2, 126.5, 126.4, 41.2, 37.8.
HRMS (ESI): m/z [M + Na]+ calcd for C21H20N2NaO2S: 387.1138;
found: 387.1138.
N-[1-(3,4-Dihydroquinolin-1(2H)-yl)-2-phenylethylidene]ben-
zenesulfonamide (3k)
Pale-yellow solid; yield: 104.9 mg (54%); mp 154–156 °C
(CH2Cl2).
IR (KBr): 2951, 1522, 1492, 1278, 1142, 1085, 744 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.0 Hz, 2 H), 7.45–
7.51 (m, 3 H), 7.10–7.18 (m, 6 H), 6.90–6.96 (m, 3 H), 4.59 (s, 2 H),
3.80–3.82 (m, 2 H), 2.21–2.23 (m, 2 H), 1.76–1.81 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 166.4, 143.7, 138.4, 134.4, 131.7,
128.6, 128.4, 128.3, 127.0, 126.6, 126.4, 126.3, 124.9, 46.3, 37.6,
25.7, 23.5.
HRMS (ESI): m/z [M + Na]+ calcd for C23H22N2NaO2S: 413.1294;
found: 413.1299.
N,2-Diphenyl-N′-(phenylsulfonyl)ethanimidamide (3l)
Pale-tan solid; yield: 152.9 mg (87%); mp 160–162 °C (CH2Cl2).
IR (KBr): 3302, 3148, 1537, 1444, 1274, 1138, 1084 cm–1.
1H NMR (400 MHz, CDCl3): δ = 9.97 (br s, 0.38 H), 7.94–7.99 (m,
2 H), 6.86–7.54 (m, 14 H), 4.50 (s, 1.21 H), 3.58 (s, 0.8 H).
13C NMR (100 MHz, CDCl3): δ = 166.5, 163.8, 143.2, 142.0, 136.7,
136.1, 134.4, 132.9, 132.4, 131.9, 130.2, 129.6, 129.5, 128.8, 128.7,
128.4, 127.1, 126.4, 125.8, 121.6, 40.6, 40.2.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18N2NaO2S: 373.0981;
Heimburger, J.; Evano, G. Chem. Sci. 2012, 3, 756.
(l) Laouiti, A.; Jouvin, K.; Bourdreux, F.; Rammah, M. M.;
Rammah, M. B.; Evano, G. Synthesis 2012, 44, 1491.
(8) For recent reports on reactions of ynamides, see:
(a) Shindoh, N.; Takemoto, Y.; Takasu, K. Chem. Eur. J.
2009, 15, 7026. (b) Cao, J.; Kong, Y.; Deng, Y.; Lai, G.; Cui,
Y.; Hu, Z.; Wang, G. Org. Biomol. Chem. 2012, 10, 9556.
(c) Yao, P.-Y.; Zhang, Y.; Hsung, R. P.; Zhao, K. Org. Lett.
2008, 10, 4275. (d) Gati, W.; Rammah, M. M.; Rammah, M.
B.; Couty, F.; Evano, G. J. Am. Chem. Soc. 2012, 134, 9078.
(e) Cao, J.; Xu, Y.; Kong, Y.; Cui, Y.; Hu, Z.; Wang, G.;
Deng, Y.; Lai, G. Org. Lett. 2012, 14, 38. (f) Garcia, P.;
Moulin, S.; Miclo, Y.; Leboeuf, D.; Gandon, V.; Aubert, C.;
Malacria, M. Chem. Eur. J. 2009, 15, 2129. (g) Garcia, P.;
Evanno, Y.; George, P.; Sevrin, M.; Ricci, G.; Malacria, M.;
Aubert, C.; Gandon, V. Org. Lett. 2011, 13, 2030. (h) Kong,
Y.; Jiang, K.; Cao, J.; Fu, L.; Yu, L.; Lai, G.; Cui, Y.; Hu, Z.;
Wang, G. Org. Lett. 2013, 15, 422. (i) Kong, Y.; Yu, L.; Fu,
L.; Cao, J.; Lai, G.; Cui, Y.; Hu, Z.; Wang, G. Synthesis
2013, 45, 1975.
found: 373.0989.
Acknowledgment
We are grateful to the National Natural Science Foundation of Chi-
na (Project No. 21102029) for financial support.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
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© Georg Thieme Verlag Stuttgart · New York
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PAPER
Birkedal, H.; Ruhland, T.; Skrydstrup, T. J. Org. Chem.
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Synthesis 2014, 46, 183–188
© Georg Thieme Verlag Stuttgart · New York