Syntheses of N-sulfonyl-N,N-disubstituted amidines via a three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes

Article abstract of DOI:10.1007/s11426-011-4405-9

A facile and efficient synthesis of N-sulfonyl-N,N-disubstituted amidines has been achieved via a CuI-catalyzed three-component free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes in the presence of azodiisobut

Full text of DOI:10.1007/s11426-011-4405-9

SCIENCE CHINA
Chemistry
February 2012 Vol.55 No.2: 214–222
doi: 10.1007/s11426-011-4405-9
• ARTICLES •
Syntheses of N-sulfonyl-N,N-disubstituted amidines via a
three-component free-radical coupling reaction of
tertiary amines and arenesulfonyl azides
with terminal alkynes
HE XinWei, SHANG YongJia*, HU JinSong, JU Kai, JIANG Wei & WANG SuFang
Key Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Key Laboratory of Molecule-Based Materials;
College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China
Received July 7, 2011; accepted August 1, 2011; published online October 28, 2011
A facile and efficient synthesis of N-sulfonyl-N,N-disubstituted amidines has been achieved via a CuI-catalyzed three-com-
ponent free-radical coupling reaction of tertiary amines and arenesulfonyl azides with terminal alkynes in the presence of azo-
diisobutyronitrile (AIBN). The reaction mechanism of this reaction has also been studied.
free radical, multicomponent reaction, sulfonyl azide, terminal alkyne
by reacting sulfonyl azides and alkynes with Schiff bases or
-ketoesters [34, 35].
1 Introduction
Amidines widely exist in natural products [36], possess
various interesting chemical properties, and have been
widely used in medical and synthetic chemistry [37]. For
example, as the building blocks for the synthesis of
iminopeptides [38, 39], antitumor and antibiotic compounds
[40], the traditional synthetic methods for amidines are
mainly based on the functional group transformation from
some precursors such as azidolactams [41], isonitriles [42],
or aldoximes [43]. Chang has improved the synthesis by
developing a tandem nucleophilic addition reaction of sul-
fonyl azides and alkynes with primary or secondary amines
[16] and has applied it for the efficient synthesis of sulfonyl
amidine derivatives. On the other hand, no tertiary amine
has been used for the synthesis of sulfonyl amidine deriva-
tives [44–46]. Herein we report a facile synthesis of
N-sulfonyl-N,N-disubstituted amidines via a MCR free rad-
ical coupling of tertiary amines and arenesulfonyl azides
with terminal alkynes (Scheme 1).
Multicomponent reactions (MCRs) offer an efficient and
straightforward route for the generation of complexity and
diversity in a single operation, and have found wide appli-
cations in combinational chemistry and drug discovery [1].
Among various MCRs recently developed [2–5], the CuI-
catalyzed MCRs of sulfonyl azides and alkynes with a third
component, like amines, water, alcohol, imines, salicylal-
dehyde, aziridine or nitroolefin have attracted increasing
research interests lately [6–15]. For example, Chang’s
[16–27] and Wang’s [28–33] groups have applied these
CuI-catalyzed MCRs on terminal alkynes respectively for
the efficient generation of N-sulfonylamidines, amides, N-
sulfonylazetidin-2-imines, iminocoumarins, 5-arylidene-2-
imino-3-pyrrolines, and γ-nitro imidates. Our group has also
applied this reaction for the efficient generation of benzoxa-
zoline-amidines and 4-arylsulfonylimino-4,5-dihydrofurans
*Corresponding author (email: shyj@mail.ahnu.edu.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com www.springerlink.com

He XW, et al. Sci China Chem February (2012) Vol.55 No.2
215
important role in this reaction. No reaction was observed
without a free radical’s initiator (Table 1, entry 18). In
comparison with diethyl azodicarboxylate (DEAD), AIBN
gave a better result (Table 1, entries 5 and 14). Thus the
optimized reaction condition was set at THF, TEA, AIBN,
80 °C and 8 h. Under this condition, the desired N,N-diethyl-
2-phenyl-N'-tosylacet amidine 4b was obtained in 82%
yield (Table 1, entry 6). The chemical structure of com-
pound 4b [47] was confirmed by X-ray analysis result as
shown in Figure 1.
To test the versatility of this reaction, the optimized reac-
tion condition was further applied for the reaction of other
arenesulfonyl azides 1 and terminal alkynes 2 with tertiary
amines 3 as summarized in Table 2. Both alkyl and aryl
alkynes can be used for this reaction, but alkyl alkynes gen-
erally give relatively high yields. The presence of either
electron-withdrawing (–Cl) or electron-donating groups
(–CH3) on arenesulfonyl azides 1 provides high yields (Ta-
ble 2, entries 1, 2, 6). Long-chain containing tertiary alkyl-
amines 3 generally give better yields of the desired products
(Table 2, entries 1, 8, 14).
To study the reaction mechanism, N,N-dimethyl-1-phen-
ylmethanamine 3d was used to substitute the alkylamine for
this reaction, from which a mixture of compounds 4 and 5
was obtained (Table 3). The NMR yield analysis shows
that the yield of compounds 4 and 5 were obtained with a
ratio close to the theoretical ratio 1:2 for this reaction. The
decrease of the yield of compound 4 in this case was at-
tributed to the electron withdrawing effect of the phenyl
substituent.
Scheme
1
Synthsis of N-sulfonylamidine derivatives 4. Reaction
conditions: CuI (0.1 equiv), AIBN (2.0 equiv), 3 (3 equiv, slow addition),
80 °C, 8 h.
2 Results and discussion
The optimized reaction conditions for the MCR of arenesul-
fonyl azides 1b and alkynes 2a with tertiary amines 3a were
obtained by varying the reaction conditions, including the
base, the solvent, the temperature, and the free radical’s
initiator, as summarized in Table 1. Triethylamine (TEA) as
base gave the best result (Table 1, entry 6). Tetrahydrofuran
(THF) as solvent afforded good yield (Table 1, entries 1–4).
The decrease of reaction time led to the great decrease of
the yield with 8 h as the optimized reaction time (Table 1,
entry 8). In addition, the free radical’s initiator played an
Table 1 Optimization of the reaction conditions for the
CuI-catalyzed three-component reactions of arenesulfonyl azide
1b and alkyne 2a with tertiary amine 3a
The ESI-MS analysis results (Scheme 2) of the reaction
mixture indicated the formation of 2,2-dimethylhexanenitrile
and methacrylonitrile when tributylamine was used. On the
other hand, the usage of N,N-dimethyl-1-phenylmethana-
mine 3d gave a mixture of two nitrile compounds (pivaloni-
trile and 2,2-dimethyl-3-phenyl propanenitrile).
On the basis of these experimental results, we proposed a
three component free radical coupling reaction mechanism
for this reaction as shown in Scheme 3. According to Chang
[16–27] and Wang [28–33], arenesulfonyl azide 1 can react
with the alkyne 2 to form the ketenimine species B in the
Temp.
(°C)
Time
(h)
8
12
8
Yield
(%)a)
Entry
Base
Solvent
Initiator
1
2
3
4
5
6
7
8
9
TEA
TEA
THF
DMF
CH3CN
CH2Cl2
THF
80
80
80
80
rt
AIBN
AIBN
AIBN
AIBN
AIBN
AIBN
AIBN
AIBN
DEAD
73
54
61
62
70
82
56
59
72
TEA
TEA
8
TEA
8
TEA b)
TEA b)
TEA b)
TEA b)
THF
80
40
80
rt
8
THF
8
THF
4
THF
8
10
11
12
13
K3PO4/TEA
Pyridine
TEA
THF
THF
THF
THF
80
rt
8
8
8
8
DEAD
DEAD
DEAD
DEAD
65
0
0–5
50
42
60
TEA
14
15
16
TEA
THF
THF
THF
THF
THF
rt
rt
8
8
DEAD
AIBN
AIBN
AIBN

51
24
0
K3PO4/TEA
Pyridine
80
80
80
8
17 K2CO3/TEA
18 TEA
10
8
72
0
a) Reaction conditions: p-tolysulfonyl azide (1.1 mmol), phenylacety-
lene (1.0 mmol), AIBN or DEAD (2.0 mmol), CuI (0.1 mmol), and TEA
(3.0 mmol), N2 atmosphere. b) 2.0 mmol.
Figure 1 X-ray crystal structure of compound 4b.

216
He XW, et al. Sci China Chem February (2012) Vol.55 No.2
Table 2 CuI-catalyzed three-component coupling reactions for the gen-
eration of N-sulfonyl-N,N-disubstituted amidines 4
There are possibly two competitive reaction routes for
the formation of compound 4 (Scheme 4): the reaction be-
tween the intermediate B and hydrogen radical and the one
between B and the free radical D. Therefore, a quantum
chemical calculation has been performed. With DFT meth-
od implemented in Gaussian 09 package [48] under
B3LYP/6-31+g** level, the reactants, products, possible
intermediates and transition state geometries along the pro-
posed reaction routes are optimized, and the reaction poten-
tial energy profiles are plotted in Figure 2. In the first step
of pathway I, the reaction between hydrogen radical and
intermediate B to form intermediate E is exothermic. The
energy released from this step is large enough for the sub-
sequent step reaction (2.4 kcal/mol). In contrast, the first
step in pathway II is endothermic, and requires about 9.6
kcal/mol energy. Thus, pathway I is dominant in the for-
mation of compound 4.
Entry
R1
R2
R3
C2H5 (3a)
3a
Yield (%) a)
4a 80
1
2
C6H5 (1a)
C6H5 (2a)
p-MeC6H4 (1b)
2a
4b 82
CH2CH2OTBS
(2b)
3
1b
3a
4c 79
4
5
1a
n-C5H11 (2c)
3a
4d 82
4e 85
4f 81
4g 82
4h 84
4i 79
4j 83
4k 86
4l 82
4m 83
4n 84
4o 83
4p 86
4q 85
4r 83
4s 81
1b
2c
3a
6
p-ClC6H4 (1c)
2c
3a
7
1a
1b
1c
1a
1b
1c
1a
1b
1a
1b
1c
1b
1a
2a
n-C4H9 (3b)
8
2a
3b
9
2a
3b
10
11
12
13
14
15
16
17
18
19
2c
3b
2c
3b
3 Conclusions
2c
3b
2a
n-C9H19 (3c)
In conclusion, we have developed a new general approach
for the convenient synthesis of N-sulfonyl-N,N-disubstituted
amidines, based on a CuI-catalyzed multicomponent free-
radical coupling reaction of arenesulfonyl azides and termi-
nal alkynes with tertiary amines. The reaction mechanism
has been studied. The usage of tertiary amine is our syn-
thetic approach as a complementary to Chang’s strategy,
might find applications for the efficient synthesis of various
N-sulfonylamidine derivatives.
2a
3c
3c
3c
3c
3b
3a
2c
2c
2c
p-MeC6H4 (2d)
2d
a) Reaction conditions: arenesulfonyl azide (1.1 mmol), phenyla-
cetylene (1.0 mmol), AIBN (2.0 mmol), CuI (0.1 mmol), and tertiary
amine (3.0 mmol), N2 atmosphere, 80 °C, 8 h.
Table 3 Using N,N-dimethyl-1-phenylmethanamine 3d as a substrate for
the synthesis of N-sulfonylamidines 4 and 5
4 Experimental section
General
All reactions were carried out using standard Schlenk tech-
niques. Et3N, CH2Cl2 and CH3CN were distilled from CaH2,
THF and toluene were distilled from sodium/benzophenone.
1H NMR and 13C NMR spectra were recorded at room tem-
perature in CDCl3 with TMS as internal standard. Chemical
shifts are reported in ppm relative to the 1H and 13C residue
signals of the deuterated solvent. IR spectra were taken with
KBr plates. Mass spectra were obtained with a mass spec-
trometer. Only characteristic fragments containing the iso-
topes of highest abundance are listed. Melting points were
measured with melting point apparatus. Single crystal X-ray
diffraction data were collected in diffractiometers. High-
resolution mass spectrometry (HRMS) was obtained using
electron spray ionization (ESI) mass spectrometry.
Yield (%) a)
Entry
R1
R2
4
5
1
2
C6H5 (1a)
C6H5 (2a)
4t
31
34
5t
35
36
p-MeC6H4 (1b)
2a
4u
5u
a) Isolated yield.
presence of CuI. Meanwhile, AIBN releases nitrogen under
heat condition to form the free radical C, which attacks
TEA (3) to generate a free radical D and methacrylonitrile
with the release of hydrogen radical. Subsequently, the hy-
drogen radical and the free radical D attack the intermediate
B to generate the target N-sulfonylamidine derivatives 4.
General procedure for the synthesis of N-sulfonyl-N,N-di-
substituted amidines
To a stirred mixture of CuI (19.1 mg, 0.1 mmol), AIBN
(328 mg, 2 mmol), p-toluenesulfonyl azide (236 mg, 1.2
mmol), phenylacetylene (102 mg, 1 mmol) in anhydrous

He XW, et al. Sci China Chem February (2012) Vol.55 No.2
217
Scheme 2 The ESI-MS analysis results for the reaction of benzenesulfonyl azide and phenylacetylene with N,N-dimethyl-1-phenylmethanamine 3d.
Scheme 3 The reaction pathway for the formation of N-sulfonylamidine derivatives 4.
Scheme 4 The two reaction routes for the generation of compound 4.
THF (5 mL) was slowly added TEA (303 mg, 3.0 mmol)
via syringe under a N2 atmosphere. Slowly raise the reaction
temperature to 80 °C and let the reaction mixture stirring for
8 h. Solvent was removed under vacuum. The residue was
washed with water, and extracted with CH2Cl2 (3 × 10 mL).
Organic layers were combined, dried over anhydrous
Na2SO4, filtered, and concentrated under vacuum. The resi-
due was purified by flash column chromatography on silica
gel (200–300 mesh) with ethyl acetate and petroleum ether
(v/v = 1:8–1:10) as eluting solvent to give the desired prod-
uct 4 and 5.
N,N-diethyl-2-phenyl-N′-(phenylsulfonyl)acetamidine (4a)
[49]
Figure 2 Calculated relative energies of the two reaction pathways in the
formation of compound 4.
1H NMR (300 MHz, CDCl3)  7.89 (d, J = 7.5 Hz, 2H,

218
He XW, et al. Sci China Chem February (2012) Vol.55 No.2
131.1, 128.4, 125.9, 64.3, 62.8, 43.2, 31.2, 31.0, 29.5, 27.4,
22.5, 14.2, 14.0, 12.1 ppm; IR (KBr) ν: 3062, 3030, 2958,
2930, 2865, 1649, 1535, 1485, 1435, 1384, 1279, 1253,
1145, 1087, 1024, 969, 896, 851, 776, 735, 686, 658, 589,
545 cm1; HRMS (ESI) calcd for C17H28N2O2S ([M+H]+)
325.1950, found 325.1961.
SO2C6H5), 7.36–7.44 (m, 3H, SO2C6H5), 7.19–.26 (m, 3H,
CH2C6H5), 7.11 (d, J = 7.5 Hz, 2H, CH2C6H5), 4.39 (s, 2H,
CH2C6H5), 3.51 (q, J = 7.2 Hz, 2H, CH2CH3), 3.21 (q, J =
6.9 Hz, 2H, CH2CH3), 1.16 (t, J = 7.2 Hz, 3H, CH2CH3),
0.96 (t, J = 7.2 Hz, 3H, CH2CH3) ppm. 13C NMR (75 MHz,
CDCl3) 164.6, 144.0, 134.3, 133.4, 131.2, 129.4, 128.9,
128.4, 127.8, 126.8, 126.2, 43.3, 36.6, 29.7, 13.4, 11.8 ppm;
IR (KBr) ν 3062, 3030, 2978, 2937, 1716, 1627, 1585, 1550,
1477, 1456, 1436, 1382, 1361, 1274, 1217, 1141, 1091,
1078, 1024, 979, 923, 896, 819, 794, 763, 721, 690, 669,
613, 569, 538, 509 cm1; HRMS (ESI) calcd for
C18H22N2O2S ([M+H]+) 331.1480, found 331.1474.
N,N-diethyl-N′-tosylnonanamidine (4e) [50]
1H NMR (300 MHz, CDCl3)  7.82 (d, J = 7.8 Hz, 2H, C6H4),
7.24 (d, J = 7.5 Hz, 2H, C6H4), 3.44 (q, J = 7.2 Hz, 2H,
NCH2CH3), 3.34 (q, J = 7.2 Hz, 2H, NCH2CH3), 2.84 (t, J =
7.2 Hz, 2H, CH2C5H11), 2.39 (s, 3H, CH3C6H4), 1.41–1.60 (m,
2H, CH2CH2C4H9), 1.29–1.39 (m, 2H, C2H4CH2C3H7),
1.23–1.25 (m, 2H, C3H6CH2C2H5), 1.13–1.23 (m, 2H,
C4H8CH2CH3), 1.08–1.13 (m, 6H, NCH2CH3), 0.88 (t, J =
6.3 Hz, 3H, C5H10CH3) ppm. 13C NMR (75 MHz, CDCl3)
 = 167.9, 143.1, 141.9, 141.4, 128.9, 126.2, 48.8, 48.3,
31.4, 31.0, 27.6, 21.8, 19.9, 13.5 ppm; IR (KBr) ν: 3062,
3028, 2956, 2872, 2858, 1708, 1596, 1541, 1465, 1431,
1369, 1274, 1165, 1147, 1087, 1024, 968, 896, 845, 812,
763, 709, 673, 596, 578, 545 cm1; HRMS (ESI) calcd for
C18H30N2O2S ([M+H]+) 339.2106, found 339.2107.
N,N-diethyl-2-phenyl-N′-tosylacetamidine (4b) [49]
1H NMR (300 MHz, CDCl3)  7.77 (d, J = 8.1 Hz, 2H,
SO2C6H4), 7.16–7.26 (m, 5H, CH2C6H5), 7.10 (d, J = 7.2
Hz, 2H, SO2C6H4), 4.38 (s, 2H, CH2C6H5), 3.50 (t, J = 7.2
Hz, 2H, CH2CH3), 3.21 (t, J = 7.2 Hz, 3H, CH2CH3), 2.36
(s, 3H, CH3C6H4), 1.16 (t, J = 6.9 Hz, 3H, CH2CH3), 0.93 (t,
J = 6.9 Hz, 3H, CH2CH3) ppm. 13C NMR (75 MHz, CDCl3)
 164.6, 141.4, 134.2, 130.6, 130.2, 130.0, 128.9, 128.8,
128.1, 126.4, 126.2, 49.0, 48.4, 36.9, 30.6, 28.9, 13.7, 13.6
ppm; IR (KBr) ν: 3060, 3028, 2991, 2951, 1716, 1627, 1585,
1477, 1456, 1436, 1385, 1361, 1274, 1217, 1141, 1091,
1078, 1024, 979, 923, 896, 819, 794, 763, 721, 690, 669,
613, 585, 545 cm1; HRMS (ESI) calcd for C19H24N2O2S
([M+H]+) 345.1636, found 345.1631.
N′-(4-chlorophenylsulfonyl)-N,N-diethylheptanamidine (4f)
[50]
1H NMR (300 MHz, CDCl3)  = 7.83 (d, J = 8.1 Hz, 2H,
SO2C6H4), 7.38 (d, J = 8.7 Hz, 2H, SO2C6H4), 3.38 (q, J =
7.5 Hz, 2H, NCH2CH3), 3.31(q, J = 7.2 Hz, 2H, NCH2CH3),
2.80 (t, J = 7.8 Hz, 2H, CH2C5H11), 1.28–1.69 (m, 8H,
CH2C4H8CH3), 1.20 (t, J = 6.6 Hz, 3H, NCH2CH3), 1.06 (t,
J = 7.2 Hz, 3H, NCH2CH3), 0.85 (t, J = 7.2 Hz, 3H,
C5H10CH3) ppm. 13C NMR (75 MHz, CDCl3)  = 167.7,
143.1, 137.2, 129.7, 129.0, 128.6, 127.5, 123.8, 121.4, 44.0,
43.3, 39.1, 36.1, 31.1, 30.2, 29.5, 28.2, 27.4, 25.6, 25.1,
24.1, 23.3, 22.7, 22.4, 19.8, 14.1, 13.9, 12.0 ppm; IR (KBr)
ν: 3091, 3062, 2956, 2933, 2872, 2237, 2017, 1722, 1583,
1548, 1477, 1436, 1386,1359, 1269, 1217, 1145, 1089,
1012, 974, 925, 893, 829, 786, 754, 707, 644, 590, 578, 543,
482 cm1; HRMS (ESI) calcd for C17H27ClN2O2S ([M+H]+)
359.1560, found 359.1554.
4-(tert-Butyldimethylsilyloxy)-N,N-diethyl-N′-tosylbutanami-
dine (4c)
1H NMR (300 MHz, CDCl3) 7.81 (d, J = 8.1 Hz, 2H,
C6H4), 7.25 (d, J = 7.8 Hz, 2H, C6H4), 3.67 (t, J = 5.4 Hz,
2H, CH2CH2CH2OTBS), 3.39–3.46 (m, 4H, CH2CH3), 2.97
(t, J = 7.8 Hz, 2H, CH2CH2CH2OTBS), 2.39 (s, 3H,
CH3C6H4), 1.87–1.96 (m, 2H, CH2CH2CH2OTBS), 1.61 (t,
J = 7.6 Hz, 2H, CH2CH3), 1.20 (t, J = 7.5 Hz, 3H, CH2CH3),
1.10 (t, J = 7.2 Hz, 3H, CH2CH3), 0.89 (s, 9H, SiC4H9),
0.05 (s, 6H, Si(CH3)2) ppm. 13C NMR (75 MHz, CDCl3) 
167.7, 141.5, 129.0, 126.0, 62.0, 43.1, 42.8, 30.7, 27.5, 25.7,
21.4, 18.1, 14.2, 12.0, -5.4 ppm; IR (KBr) ν: 3062, 3028,
2961, 2930, 2865, 1649, 1535, 1485, 1435, 1384, 1279,
1253, 1145, 1087, 1078, 969, 898, 851, 776, 735, 685, 658,
585, 505 cm1; HRMS (ESI) calcd for C21H38N2O3SSi
([M+H]+) 427.2451, found 427.2459.
N,N-dibutyl-2-phenyl-N′-(phenylsulfonyl)acetamidine (4g)
1H NMR (300 MHz, CDCl3)  = 7.89 (d, J = 7.2 Hz, 2H,
SO2C6H5), 7.36–7.44 (m, 3H, SO2C6H5), 7.13–7.28 (m, 5H,
CH2C6H5), 4.39 (s, 2H, CH2C6H5), 3.40 (t, J = 7.5 Hz, 2H,
NCH2C3H7), 3.11 (t, J = 7.5 Hz, 2H, NCH2C3H7), 1.11–1.71
(m, 8H, NCH2C2H4CH3), 0.77–0.86 (m, 6H, NC3H6CH3)
ppm. 13C NMR (75 MHz, CDCl3)  = 164.7, 144.2, 134.5,
131.2, 128.9, 128.3, 127.9, 126.8, 126.1, 48.8, 36.9, 30.4,
28.6, 20.1, 13.6 ppm; IR (KBr) ν: 3062, 3028, 2958, 2931,
2872, 2231, 1585, 1544, 1467, 1431, 1373, 1276, 1195,
1143, 1087, 1024, 952, 904, 848, 756, 729, 690, 624, 586,
534, 518 cm1; HRMS (ESI) calcd for C22H30N2O2S
N,N-diethyl-N′-(phenylsulfonyl)nonanamidine (4d) [50]
1H NMR (300 MHz, CDCl3)  7.87–7.90 (m, 3H, C6H5),
7.37–7.41 (m, 2H, C6H5), 3.39 (q, J = 7.2 Hz, 2H,
NCH2CH3), 3.30 (q, J = 6.9 Hz, 2H, NCH2CH3), 2.80 (t, J =
7.8 Hz, 2H, CH2C5H11), 1.52–1.60 (m, 2H, CH2CH2C4H9),
1.32–1.37 (m, 2H, C2H4CH2C3H7), 1.19–1.25 (m, 2H,
C3H6CH2C2H5), 1.15–1.17 (m, 2H, C4H8CH2CH3), 1.02–
1.07 (m, 6H, NCH2CH3), 0.84 (t, J = 6.3 Hz, 3H, C5H10CH3)
ppm. 13C NMR (75 MHz, CDCl3)  167.7, 144.6, 134.1,

He XW, et al. Sci China Chem February (2012) Vol.55 No.2
219
([M+H]+) 387.2106, found 387.2107.
3H, SO2C6H5CH3), 1.44–1.59 (m, 8H, CH2C4H8CH3),
1.20–1.27 (m, 8H, NCH2C2H4CH3), 0.78–0.93 (m, 9H,
NC3H6CH3, C5H10CH3) ppm. 13C NMR (75 MHz, CDCl3)
 = 167.8, 141.9, 141.4, 129.4, 129.1, 129.0, 128.9, 127.2,
126.0, 48.8, 31.0, 29.6, 28.9, 27.4, 22.5, 21.4, 20.1, 14.0,
13.7 ppm; IR (KBr) ν: 3062, 3030, 2956, 2872, 2858, 1708,
1598, 1541, 1465, 1431, 1355, 1325, 1274, 1165, 1145,
1087, 1018, 968, 896, 852, 812, 763, 709, 673, 596, 578,
547 cm1; HRMS (ESI) calcd for C22H38N2O2S ([M+H]+)
395.2732, found 395.2724.
N,N-dibutyl-2-phenyl-N′-tosylacetamidine (4h)
1H NMR (300 MHz, CDCl3)  = 7.77 (d, J = 7.8 Hz, 2H,
SO2C6H4), 7.23 (d, J = 6.9 Hz, 2H, SO2C6H4), 7.15–7.18 (m,
5H, CH2C6H5), 4.38 (s, 2H, CH2C6H5), 3.39 (t, J = 6.6 Hz,
2H, NCH2C3H7), 3.09 (t, J = 6.9 Hz, 2H, NCH2C3H7), 2.35
(s, 3H, SO2C6H4CH3), 1.50–1.55 (m, 4H, NC2H4CH2CH3),
1.11–1.25 (m, 4H, NCH2CH2C2H5), 0.78–0.86 (m, 6H,
NC3H6CH3) ppm. 13C NMR (75 MHz, CDCl3)  = 164.6,
141.6, 141.4, 134.5, 128.9, 128.8, 127.9, 126.7, 126.1, 49.0,
48.8, 36.8, 30.4, 28.7, 21.4, 20.2, 19.9, 13.7, 13.6 ppm; IR
(KBr) ν:3061, 3026, 2954, 2929, 2872, 1574, 1552, 1473,
1471, 1371, 1276, 1261, 1199, 1182, 1136, 1083, 1018, 950,
912, 856, 813, 727, 692, 655, 596, 549,501 cm1; HRMS
(ESI) calcd for C23H32N2O2S ([M+H]+) 401.2263, found
401.2261.
N,N-dibutyl-N′-(4-chlorophenylsulfonyl)heptanamidine (4l)
1H NMR (300 MHz, CDCl3)  = 7.81 (d, J = 8.1 Hz, 2H,
SO2C6H4), 7.36 (d, J = 7.8 Hz, 2H, SO2C6H4), 3.29 (t, J =
7.5 Hz, 2H, NCH2C3H7), 3.21 (t, J = 7.5 Hz, 2H,
NCH2C3H7), 2.80 (t, J = 8.4 Hz, 2H, CH2C5H11), 2.24–2.39
(m, 4H, NCH2CH2C2H5), 1.21–1.28 (m, 8H, CH2C4H8CH3),
0.84–0.89 (m, 9H, NC3H6CH3, C5H10CH3) ppm. 13C NMR
(75 MHz, CDCl3)  = 167.9, 143.2, 137.2, 128.5, 127.5,
53.6, 48.9, 48.7, 41.7, 31.2, 29.5, 28.7, 28.0, 27.4, 26.6,
25.1, 22.5, 20.7, 20.0, 15.6, 14.0, 13.7 ppm; IR (KBr) ν:
3062,3028, 2958, 2931, 2872, 2233, 2019, 1635, 1544,
1475, 1431, 1379, 1286, 1271, 1193, 1170, 1145, 1087,
1012, 947, 896, 852, 827,756, 731, 707, 655, 626, 588, 555,
530, 482 cm1; HRMS (ESI) calcd for C21H35ClN2O2S
([M+H]+) 415.2186, found 415.2186.
N,N-dibutyl-N′-(4-chlorophenylsulfonyl)-2-phenylacetamidine
(4i)
1H NMR (300 MHz, CDCl3)  = 7.77 (d, J = 8.1 Hz, 2H,
SO2C6H4), 7.33 (d, J = 8.7 Hz, 2H, SO2C6H4), 7.09–7.28 (m,
5H, CH2C6H5), 4.36 (s, 2H, CH2C6H5), 3.39 (t, J = 7.8 Hz,
2H, NCH2C3H7), 3.11 (t, J = 7.5 Hz, 2H, NCH2C3H7),
1.10–1.68 (m, 8H, NCH2C2H4CH3), 0.78–0.87 (m, 6H,
NC3H6CH3) ppm. 13C NMR (75 MHz, CDCl3)  = 164.8,
142.7, 137.4, 134.1, 128.9, 128.5, 127.8, 127.7, 126.9, 49.1,
48.9, 36.8, 30.5, 28.6, 20.2, 19.8, 13.7, 13.5 ppm; IR (KBr)
ν: 3064, 3028, 2956, 2872, 1552, 1465, 1452, 1373, 1276,
1257, 1199, 1134, 1087, 1010, 974, 950, 904, 862, 823, 758,
719, 655, 590, 528, 491, 453 cm1; HRMS (ESI) calcd for
C22H29ClN2O2S ([M+H]+) 421.1716, found 421.1706.
N,N-dinonyl-2-phenyl-N′-(phenylsulfonyl)acetamidine (4m)
1H NMR (300 MHz, CDCl3)  = 7.88 (d, J = 8.1 Hz, 2H,
SO2C6H5), 7.37–7.40 (m, 3H, SO2C6H5), 7.14–7.24 (m, 5H,
CH2C6H5), 4.38 (s, 2H, CH2C6H5), 3.38 (t, J = 6.7 Hz, 2H,
CH2C8H17), 3.08 (t, J = 6.8 Hz, 2H, CH2C8H17), 1.18–1.49
(m, 28H, CH2C7H14CH3), 0.78–0.87 (m, 6H, CH2C7H14CH3)
ppm. 13C NMR (75 MHz, CDCl3)  = 164.7, 144.2, 134.5,
131.2, 128.8, 128.6, 128.3, 127.9, 126.8, 126.2, 126.1, 53.3,
49.3, 49.1, 36.9, 31.9, 31.6, 29.6, 29.4, 29.1, 28.4, 27.4,
26.9, 26.6, 25.7, 22.6, 14.1 ppm; IR (KBr) ν: 3062, 3028,
2926, 2854, 2235, 1672, 1606, 1585, 1548, 1467, 1454,
1431, 1375, 1278, 1145, 1089, 1024, 999, 952, 902, 846,
754, 727, 690, 626, 586, 557 cm1; HRMS (ESI) calcd for
C32H50N2O2S ([M+H]+) 527.3671, found 527.3672.
N,N-dibutyl-N′-(phenylsulfonyl)heptanamidine (4j)
1H NMR (300 MHz, CDCl3)  = 7.89 (d, J = 7.5 Hz, 2H,
C6H5), 7.87 (d, J = 7.8 Hz, 1H, C6H5), 7.37–7.39 (m, 2H,
C6H5), 3.29 (t, J = 7.5 Hz, 2H, NCH2C3H7), 3.20 (t, J = 7.8
Hz, 2H, NCH2C3H7), 2.80 (t, J = 5.4 Hz, 2H, CH2C5H11),
1.39–1.61 (m, 8H, CH2C4H8CH3), 1.06–1.27 (m, 8H,
NCH2C2H4CH3), 0.75–0.92 (m, 9H, NC3H6CH3, C5H10CH3)
ppm. 13C NMR (75 MHz, CDCl3)  = 167.8, 144.6, 131.1,
128.3, 125.9, 53.5, 48.8, 48.7, 47.5, 45.6, 31.2, 31.1, 29.9,
29.5, 28.9, 28.5, 27.3, 26.2, 22.5, 20.7, 20.2, 20.1, 20.0,
14.0, 13.7, 9.6 ppm; IR (KBr) ν: 3062, 3028, 2958, 2931,
2872, 1645, 1544, 1479, 1465, 1431, 1375, 1276, 1193,
1145, 1087, 997, 896, 852, 754, 729, 690, 669, 626, 586,
530 cm1; HRMS (ESI) calcd for C21H36N2O2S ([M+H]+)
381.2575 found 381.2571.
N,N-dinonyl-2-phenyl-N′-tosylacetamidine (4n)
1H NMR (300 MHz, CDCl3)  = 7.76 (d, J = 7.8 Hz, 2H,
SO2C6H4), 7.13–7.23 (m, 7H, SO2C6H4, CH2C6H5), 4.36 (s,
2H, CH2C6H5), 3.37 (t, J = 6.7 Hz, 2H, CH2C7H14CH3),
3.07 (t, J = 6.8 Hz, 2H, CH2C7H14CH3), 2.34 (s, 3H,
SO2C6H4CH3), 1.18–1.51 (m, 28H, CH2C7H14CH3), 0.78–
0.86 (m, 6H, CH2C7H14CH3) ppm. 13C NMR (75 MHz,
CDCl3)  = 164.6, 141.5, 141.4, 134.5, 128.9, 128.8, 127.9,
126.7, 126.1, 49.2, 49.0, 36.8, 31.7, 31.6, 29.5, 29.2, 28.4,
26.9, 26.6, 22.6, 21.3, 14.1 ppm; IR (KBr) ν:3030, 2954,
2926, 2854, 1716, 1608, 1548, 1489, 1465, 1456, 1377,
1346, 1298, 1282, 1147, 1089, 1020, 950, 883, 850, 813,
N,N-dibutyl-N′-tosylheptanamidine (4k) [50]
1H NMR (300 MHz, CDCl3)  = 7.78 (d, J = 7.5 Hz, 2H,
SO2C6H5), 7.20 (d, J = 7.5 Hz, 2H, SO2C6H5), 3.33 (t, J =
6.9 Hz, 2H, NCH2C3H7), 3.21 (t, J = 6.6 Hz, 2H,
NCH2C3H7), 2.82 (t, J = 7.5 Hz, 2H, CH2C5H11), 2.36 (s,

220
He XW, et al. Sci China Chem February (2012) Vol.55 No.2
761, 723, 707, 677, 597, 580, 553 cm1; HRMS (ESI) calcd
for C33H52N2O2S ([M+H]+) 541.3828, found 541.3827.
3.07 (t, J = 7.2 Hz, 2H, CH2C6H4), 2.40 (s, 4H, NCH2C3H7),
2.36 (s, 3H, SO2C6H4CH3), 2.32 (s, 3H, CH2C6H4CH3),
1.21–1.50 (m, 8H, NCH2C2H4CH3), 0.86–0.90 (m, 6H,
C3H6CH3) ppm. 13C NMR (75 MHz, CDCl3) δ = 164.4,
144.6, 142.9, 136.7, 130.3, 129.4, 127.7, 126.9, 125.8,
124.4, 120.6, 117.0, 48.1, 30.8, 29.7, 29.2, 24.6, 21.4, 21.2,
19.9, 13.6 ppm; IR (KBr) ν: 3051, 3028, 2958, 2929, 2872,
1716, 1670, 1635, 1597, 1512, 1490, 1458, 1379, 1330,
1261, 1159, 1145, 1089, 1016, 921, 813, 754, 704, 655, 584,
569, 549, 522, 509 cm1; HRMS (ESI) calcd for C24H34N2O2S
([M+H]+) 415.2419, found 415.2415.
N,N-dinonyl-N′-(phenylsulfonyl)heptanamidine (4o)
1H NMR (300 MHz, CDCl3)  = 7.90 (d, J = 7.6 Hz, 2H,
C6H5), 7.40–7.43 (m, 3H, C6H5), 3.31 (t, J = 7.2 Hz, 2H,
NCH2C8H17), 3.21 (t, J = 7.2 Hz, 2H, NCH2C8H17), 2.83 (t,
J = 7.8 Hz, 2H, CH2C5H11), 1.61–1.73 (m, 14H,
CH2C7H14CH3), 1.45–1.61 (m, 14H, CH2C7H14CH3), 1.39–
1.44 (m, 8H, CH2C4H8CH3), 1.16 (t, J = 7.3 Hz, 3H,
C5H10CH3), 0.87 (t, J = 7.3 Hz, 6H, C8H16CH3) ppm. 13C
NMR (75 MHz, CDCl3)  = 167.8, 144.6, 131.1, 128.3,
125.9, 121.4, 49.1, 49.0, 39.3, 31.8, 31.7, 31.2, 29.6, 29.2,
28.9, 27.3, 26.9, 26.8, 23.4, 22.6, 22.4, 14.1 ppm; IR (KBr)
ν: 3064, 2926, 2854, 2241, 2019, 1544, 1463, 1379, 1278,
1228, 1147, 1089, 1024, 850, 754, 729, 690, 628, 590, 565
cm1; HRMS (ESI) calcd for C31H56N2O2S ([M+H]+)
521.4140 found 521.4132.
N,N-diethyl-N′-(phenylsulfonyl)-2-p-tolylacetamidine (4s)
1H NMR (300 MHz, CDCl3)  = 8.09 (d, J = 6.9 Hz, 2H,
SO2C6H5), 7.67–7.90 (m, 3H, SO2C6H5), 7.47 (d, J = 8.1 Hz,
2H, CH2C6H4CH3), 7.23 (d, J = 6.9 Hz, 2H, CH2C6H4CH3),
2.62 (s, 2H, CH2C6H4CH3), 2.34 (s, 3H, CH2C6H4CH3),
2.28 (q, J = 5.4 Hz, 4H, NCH2CH3), 2.23 (t, J = 7.2 Hz, 6H,
NCH2CH3) ppm. 13C NMR (75 MHz, CDCl3)  = 163.7,
148.1, 135.3, 133.8, 132.7, 129.7, 129.6, 129.4, 128.9,
126.0, 125.8, 41.9, 39.2, 31.8, 29.3, 22.6, 14.0 ppm; IR
(KBr) ν: 3060, 3028, 2991, 2951, 1716, 1627, 1585, 1477,
1456, 1436, 1385, 1361, 1274, 1217, 1141, 1091, 1078,
1024, 979, 923, 896, 819, 794, 763, 721, 690, 669, 613, 585,
545 cm1; HRMS (ESI) calcd for C19H24N2O2S ([M+H]+)
345.1592, found 345.1576.
N,N-dinonyl-N′-tosylheptanamidine (4p)
1H NMR (300 MHz, CDCl3)  = 7.69 (d, J = 7.2 Hz, 2H,
SO2C6H4), 7.13 (d, J = 7.5 Hz, 2H, SO2C6H4), 3.24 (t, J =
7.8 Hz, 2H, CH2C7H14CH3), 3.14 (t, J = 7.5 Hz, 2H,
CH2C7H14CH3), 2.73 (t, J = 8.1 Hz, 2H, CH2C5H11), 2.34 (s,
3H, SO2C6H4 CH3), 1.42–1.61 (m, 28H, NCH2C7H14CH3),
1.09–1.17(m, 8H, CH2C4H8CH3), 0.73–0.79 (m, 9H,
NC8H16CH3, C5H10CH3) ppm. 13C NMR (75 MHz, CDCl3)
 = 167.6, 141.9, 141.3, 130.3, 130.1, 129.4, 129.1, 128.8,
128.3, 125.8, 121.4, 120.3, 118.9, 67.9, 48.9, 48.7, 39.2,
31.6, 31.1, 30.8, 29.4, 28.9, 27.2, 26.6, 24.9, 23.0, 22.4,
21.2, 13.8 ppm; IR (KBr) ν:3028, 2954, 2854, 2239, 1681,
1598, 1544, 1463, 1379, 1274, 1145, 1112, 1041, 1012, 898,
850, 813, 721, 707, 688, 590, 553, 482 cm1; HRMS (ESI)
calcd for C32H58N2O2S ([M+H]+) 535.4297, found 535.4303.
N,N-dimethyl-2-phenyl-N′-(phenylsulfonyl)acetamidine (4t)
1H NMR (300 MHz, CDCl3)  = 7.44 (d, J = 7.5 Hz, 2H,
SO2C6H4), 7.11–7.24 (m, 8H, SO2C6H4, CH2C6H5), 2.41 (s,
2H, CH2C6H5), 2.36 (s, 6H, NCH3), ppm. 13C NMR (75
MHz, CDCl3)  = 164.7, 144.6, 142.1, 140.3, 136.5, 130.2,
129.4, 127.6, 124.6, 63.2, 40.5, 21.7 ppm; IR (KBr) ν: 3065,
3032, 2956, 2916, 2358, 1928, 1890, 1749, 1635, 1589,
1489, 1398, 1377, 1323, 1300, 1290, 1209, 1161, 1139,
1105, 1076, 1035, 1012, 815, 806, 704, 651, 584, 520, 505,
484 cm1; HRMS (ESI) calcd for C16H18N2O2S ([M+H]+)
303.1167, found 303.1143.
N′-(4-chlorophenylsulfonyl)-N,N-dinonylheptanamidine (4q)
1H NMR (300 MHz, CDCl3)  = 7.81 (d, J = 8.4 Hz, 2H,
SO2C6H4), 7.34 (d, J = 7.8 Hz, 2H, SO2C6H4), 3.26 (t, J =
7.5 Hz, 2H, CH2C7H14CH3), 3.19 (t, J = 7.5 Hz, 2H,
NCH2C7H14CH3), 2.79 (t, J = 8.4 Hz, 2H, CH2C5H11), 2.34–
2.36 (m, J = 8.6 Hz, 2H, CH2CH2C4H9), 1.12–1.62 (m, 34H,
NCH2C7H14CH3, C2H4C3H6CH3), 0.79–0.84 (m, 9H,
NCH2C7H14CH3, C5H10CH3) ppm. 13C NMR (75 MHz,
CDCl3)  = 167.8, 143.3, 137.2, 128.5, 127.5, 53.9, 49.4,
49.0, 31.8, 31.7, 31.2, 29.5, 29.3, 29.1, 28.9, 27.5, 27.4,
26.8, 26.7, 26.4, 22.6, 22.4, 14.0 ppm; IR (KBr) ν:3088,
3057, 2954, 2926, 2852, 1573, 1544, 1467, 1435, 1375, 1286,
1259, 1143, 1087, 1012, 985, 898, 854, 829, 792, 756, 723,
707, 678, 657, 572, 538, 513, 480 cm1; HRMS (ESI) calcd
for C31H55ClN2O2S ([M+H]+) 555.3751, found 555.3740.
N,N-dimethyl-2-phenyl-N′-tosylacetamidine (4u) [51]
1H NMR (300 MHz, CDCl3)  = 7.63 (d, J = 7.8 Hz, 2H,
SO2C6H4), 7.40 (d, J = 7.5 Hz, 2H, SO2C6H4), 7.25–7.32 (m,
5H, CH2C6H5), 2.65 (s, 8H, CH2C6H5, NCH3), 2.41 (s, 3H,
CH3C6H4SO2) ppm. 13C NMR (75 MHz, CDCl3)  = 164.7,
144.6, 142.1, 140.2, 136.4, 130.2, 129.4, 128.7, 127.6,
124.5, 63.1, 40.6, 21.7, 21.5 ppm; IR (KBr) ν: 3065, 3032,
2956, 2916, 2358, 1928, 1890, 1749, 1635, 1589, 1489,
1398, 1377, 1323, 1300, 1290, 1209, 1161, 1139, 1105,
1076, 1035, 1012, 815, 806, 704, 651, 584, 520, 505, 484
cm1; HRMS (ESI) calcd for C17H20N2O2S ([M+H]+)
317.1324, found 317.1642.
N,N-dibutyl-2-p-tolyl-N′-tosylacetamidine (4r)
1H NMR (300 MHz, CDCl3)  = 7.71 (d, J = 7.5 Hz, 2H,
SO2C6H4), 7.66 (d, J = 7.8 Hz, 2H, SO2C6H4), 7.43 (d, J =
8.1 Hz, 2H, CH2C6H4), 7.25 (d, J = 7.8 Hz, 2H, CH2C6H4),
N-benzyl-N-methyl-2-phenyl-N′-(phenylsulfonyl)acetamidine
(5t)
1H NMR (300 MHz, CDCl3)  7.57 (d, J = 7.2 Hz, 2H,

He XW, et al. Sci China Chem February (2012) Vol.55 No.2
221
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SO2C6H5), 7.25–7.33 (m, 3H, SO2C6H5), 7.16–7.21 (m, 5H,
NCH2C6H5), 7.04–7.11 (m, 5H, CH2C6H5), 5.12 (s, 2H,
NCH2C6H5), 3.96 (s, 2H, CH2C6H5), 2.53 (s, 3H, CH3) ppm.
13C NMR (75 MHz, CDCl3)  = 172.2, 143.0, 136.8, 131.2,
130.7, 130.4, 129.6, 129.1, 128.3, 127.9, 126.6, 126.1, 61.6,
42.9, 42.0 ppm; IR (KBr) ν: 3462, 3061, 3030, 2927, 2756,
2235, 1732, 1714, 1556, 1479, 1444, 1386, 1338, 1265,
1136, 1076, 1022, 999, 954, 842, 775, 742, 690, 648, 584,
532, 472 cm1; HRMS (ESI) calcd for C22H22N2O2S
([M+H]+) 379.1480, found 379.1471.
N-benzyl-N-methyl-2-phenyl-N′-tosylacetamidine (5u)
1H NMR (300 MHz, CDCl3)  7.92 (d, J = 6.9 Hz, 2H,
SO2C6H4), 7.81 (d, J = 6.9 Hz, 2H, SO2C6H4), 7.41–7.46 (m,
5H, CH2C6H5), 7.26–7.37 (m, 5H, NCH2C6H5), 3.54 (s, 2H,
NCH2C6H5), 2.31 (s, 6H, NCH3, CH3SO2C6H4), 2.01 (s, 2H,
CH2C6H5) ppm. 13C NMR (75 MHz, CDCl3)  165.1, 146.3,
141.8, 137.6, 131.2, 130.8, 130.4, 130.0, 129.4, 128.7,
128.6, 124.4, 121.4, 114.1, 39.3, 23.4, 21.8, 21.5 ppm; IR
(KBr) ν: 3566, 2956, 2924, 2848, 2343, 2322, 1749, 1716,
1674, 1647, 1558, 1506, 1489, 1456, 1394, 1377, 1024, 893,
858, 763, 696, 669, 648, 586, 518 cm1; HRMS (ESI) calcd
for C23H24N2O2S ([M+H]+) 393.1636, found 393.1625.
We thank the National Natural Science Foundation of China (20872001),
the Anhui Education Department (TD200707 & KJ2008A064), the Pro-
gram for the NCET (NCET-10-0004), and the Research Culture Funds of
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