Copper-catalyzed tandem synthesis of highly functionalized bisamidines

Article abstract of DOI:10.1055/s-0032-1317952

The synthesis of a novel class of bisamidines via a copper-catalyzed tandem reaction of trichloroacetonitrile, primary amines, sulfonyl azides, and terminal alkynes is described. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317952

LETTER
▌161
lCettoerpper-Catalyzed Tandem Synthesis of Highly Functionalized Bisamidines
Synthesis of Highly Functionalized Bisamidines
Issa Yavari,* Manijeh Nematpour, Esmat Sodagar
Department of Chemistry, Tarbiat Modares University, PO Box 14115-175 Tehran, Iran
Fax +98(21)82883455; E-mail: yavarisa@modares.ac.ir
Received: 08.10.2012; Accepted after revision: 05.12.2012
give the bisamidines 6 in moderate to good yields (Table
Abstract: The synthesis of a novel class of bisamidines via a cop-
1). Herein, we report the details of this work.33
per-catalyzed tandem reaction of trichloroacetonitrile, primary
amines, sulfonyl azides, and terminal alkynes is described.
First, p-toluenesulfonyl azide (1a), phenylacetylene (2a),
benzylamine (3a), and (4) were selected as the model sub-
strates. Several catalysts such as CuI, CuBr, CuCl, Cu2O,
and copper powder were tested with CuI giving the best
results. Among several solvents screened, MeCN was the
best. When the reaction was performed in MeCN in the
presence of one equivalent of Et3N at room temperature
for eight hours, it was found that the desired product 6a
was indeed obtained in 84% yield (Table 1). Thus, the op-
timized reaction conditions used were 10 mol% of CuI, 1
mmol of 1, 1.2 mmol of 2, 1 mmol of 3, and 1 mmol of 4
in MeCN at room temperature.
Keywords: bisamidines, ketenimines, tandem reaction, sulfonyl
azide, terminal alkyne, trichloroacetonitrile
In recent years, various multicomponent reactions (MCR)
have been developed not only for their simplicity and ef-
ficiency, but also for their economy in organic synthesis.1
Amidines could be well-fitted for these criteria since they
are prominent structural motifs in numerous bioactive nat-
ural products.2 Furthermore, they serve as pharmacoph-
ores, synthetic intermediates, and efficient coordinating
ligands.3,4 The benzamidine variant is often employed as
an excellent guanidine surrogate in medicinal chemistry.5
Consequently, a number of synthetic methods have been
developed for the preparation of amidines.6,7 Most of
these methods rely on the nucleophilic addition of amines
or ammonia equivalents to nitriles under forcing condi-
tions or to suitably activated carboxylate equivalents.8
Phenylacetylene readily participates in the coupling to
furnish the corresponding bisamidines 6a–h in good
yields (Table 1). Aliphatic acetylenes served as substrates
compared to phenylacetylene. Aromatic and aliphatic sul-
fonyl azides reacted efficiently, and the corresponding
products were obtained in good yields.
The sharp singlet at about δ = 10 ppm for the NH is indic-
ative for the hydrogen bonding in 6 (as drawn in Table 1).
The trichloromethyl unit is a structural feature present in
a vast number of bioactive natural products and pharma-
ceuticals, and it was found to be the key component for
potent activity and low toxicity in some cases.9–12 Incor-
poration of the trichloromethyl subunit can result in high-
er metabolism and improved biological properties of a
target drug candidate. Scaffolds derived from the tri-
chloromethyl subunit have been exploited for their utility
as versatile synthetic intermediates.13–16
Ketenimines,17 as useful intermediates, have attracted
much attention due to their diverse chemistry and relative
reactivity.18–22 Due to the activity of the central carbon
atom of ketenimines towards various nucleophiles,23–28
they are applied in the construction of heterocycles. Per-
haps, the most attractive method for generation of keten-
A plausible mechanism for the formation of compounds 6
is given in Scheme 1. The yellow copper acetylide 7,
formed from 1 and CuI, undergoes a 1,3-dipolar cycload-
dition reaction with sulfonyl azide 2 to generate the tri-
azole derivative 8.34 This intermediate can undergo ring-
opening reaction to afford form α-diazoimino species 9
and thereafter ketenimine 10 by elimination of nitrogen
gas.35,36 Amidine derivative 5 [formed from 3 and 4] un-
dergoes a nucleophilic addition reaction with 10 to afford
bisamidine 6.
SO2R2
R1
Cu
N2
R1
N
2
R1
Cu
1 + CuI
N
N
SO2R2
Cu
N
8
imines
is
the
copper-catalyzed
azide–alkyne
7
9
cycloaddition (Table 1).29,30 This method is well suited for
MCR.31 Thus, the generation of ketenimine intermediates
from terminal alkynes, sulfonyl azides, and triethylamine,
as the base, in the presence of copper catalysts,32 has en-
couraged us to trap these intermediates with 2,2,2-trichlo-
ro-N-alkylacetamidines (5) [generated from primary
alkylamines (3) and trichloroacetonitrile (4) in MeCN], to
R3NH2
Cl3CCN
+
4
3
NH
R3
N
CCl3
H
H
H+
5
C
C
NSO2R2
10
6
R1
– N2
SYNLETT 2013, 24, 0161–0164
Advanced online publication: 08.01.2013
DOI: 10.1055/s-0032-1317952; Art ID: ST-2012-D0861-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Scheme 1

162
I. Yavari et al.
LETTER
Table 1 Copper-Catalyzed Azide–Alkyne Cycloaddition for the Synthesis of 6
R3NH2
Cl3CCN
+
3
4
MeCN, r.t.
NH
O
R3
N
O
O
O
R1
CCl3
S
H
R3
S
H
R2
R1
N
N
CuI (10 mol%)
Et3N, MeCN
H
N
R2
1
5
C
+
N
6
CCl3
O
O
r.t., 8 h
R1
S
R2
N3
2
Entry
1, 2, 3, 6
R1
R2
R3
Yield of 6 (%)
1
2
a
b
c
d
e
f
Ph
4-Tol
Ph
Bn
Bn
Bn
84
80
74
78
73
70
81
78
69
64
60
57
Ph
3
Ph
Me
4
Ph
4-Tol
Ph
4-ClC6H4CH2
5
Ph
4-ClC6H4CH2
4-ClC6H4CH2
4-TolCH2
4-TolCH2
Bn
6
Ph
Me
7
g
h
i
Ph
4-Tol
Ph
8
Ph
9
n-Pr
n-Pr
Me
10
11
12
j
4-Tol
Ph
4-ClC6H4CH2
Bn
k
l
n-Bu
n-Bu
Me
Bn
S.; Rathelot, P.; Vanelle, P. Bioorg. Med. Chem. 2009, 17,
4313.
In conclusion, we have developed a one-pot, cascade syn-
thesis of novel derivatives of bisamidines, containing a
trichloromethyl group, via a copper-catalyzed reaction of
trichloroacetonitrile, primary alkylamines, sulfonyl
azides, and terminal alkynes in moderate to good yields.
(12) Beaumont, S.; Ilardi, E. A.; Monroe, L. R.; Zakarian, A.
J. Am. Chem. Soc. 2010, 132, 1482.
(13) Rudyakova, E. V.; Evstafeva, I. T.; Rozentsveig, I. B.;
Mirskova, A.; Levkovskaya, G. G. Russ. J. Org. Chem.
2006, 42, 981.
(14) Zajac, M.; Peters, R. Chem. Eur. J. 2009, 15, 8204.
(15) Mangelinckx, S.; Boeykens, M.; De Kimpe, N. Synlett 2008,
1394.
(16) Fesenko, A. A.; Solovyev, P. A.; Shutalev, A. D.
Tetrahedron 2010, 66, 940.
(17) Staudinger, H.; Hauser, E. Helv. Chim. Acta 1921, 4, 887.
(18) Lu, P.; Wang, Y. G. Synlett 2010, 166.
(19) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302.
(20) Yavari, I.; Nematpour, M.; Ghazanfarpour-Darjani, M.
Tetrahedron Lett. 2012, 53, 942.
(21) Yavari, I.; Nematpour, M.; Yavari, S.; Sadeghizadeh, F.
Tetrahedron Lett. 2012, 53, 1889.
(22) Yoo, E. J.; Chang, S. Curr. Org. Chem. 2009, 13, 1766.
(23) Krow, G. R. Angew. Chem., Int. Ed. Engl. 1971, 10, 435.
(24) Bae, I.; Han, H.; Chang, S. J. Am. Chem. Soc. 2005, 127,
2038.
(25) Yoo, E. J.; Bae, I.; Cho, S. H.; Han, H.; Chang, S. Org. Lett.
2006, 8, 1347.
(26) Cho, S. H.; Chang, S. Angew. Chem. Int. Ed. 2008, 47, 2836.
(27) Shang, Y. J.; Ju, K.; He, X. W.; Hu, J. S.; Yu, S. Y.; Zhang,
M.; Liao, K. S.; Wang, L. F.; Zhang, P. J. Org. Chem. 2010,
75, 5743.
References and Notes
(1) Wasilke, J. C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. Rev. 2005, 105, 1001.
(2) Greenhill, J. V.; Lue, P. Prog. Med. Chem. 1993, 30, 203.
(3) Boyd, G. V. In The Chemistry of Amidines and Imidates;
Vol. 2; Patai, S.; Rappoport, Z., Eds.; Chap. 8; Wiley: New
York, 1991.
(4) Barker, J.; Kilner, M. Coord. Chem. Rev. 1994, 133, 219.
(5) Patai, S.; Rappoport, Z. The Chemistry of Amidines and
Imidates; Vol. 27; Wiley: New York, 1991.
(6) Cui, S.; Wang, J.; Wang, Y. Org. Lett. 2008, 10, 7.
(7) Yavari, I.; Ahmadian, S.; Ghazanfarpur-Darjani, M.; Solgi,
Y. Tetrahedron Lett. 2011, 52, 668.
(8) Katritzky, A. R.; Cai, C. M.; Singh, S. K. J. Org. Chem.
2006, 71, 3375.
(9) Faulkner, D. J. Nat. Prod. Rep. 1997, 14, 259.
(10) Sitachitta, P. N.; Rossi, J.; Roberts, M. A.; Gerwick, W. H.;
Fletcher, M. D.; Willis, C. L. J. Am. Chem. Soc. 1998, 120,
7131.
(11) Verhaeghe, P.; Azas, N.; Hutter, S.; Castera-Ducros, C.;
Laget, M.; Dumètre, A.; Gasquet, M.; Reboul, J.-P.; Rault,
Synlett 2013, 24, 161–164
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Highly Functionalized Bisamidines
163
(28) Wang, J.; Wang, J. J.; Zhu, Y. X.; Lu, P.; Wang, Y. G. Chem.
Commun. 2011, 3275.
H, m, Ph), 7.47–7.50 (4 H, m, Ph), 7.58 (1 H, t, 3J = 7.4 Hz,
Ar), 7.98 (2 H, d, 3J = 7.9 Hz, Ar), 10.29 (1 H, s, NH). 13
C
(29) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K.
B. Angew. Chem. Int. Ed. 2002, 41, 2596.
(30) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057.
(31) Jin, H.; Zhou, B.; Wu, Z.; Shen, Y.; Wang, Y. Tetrahedron
2011, 67, 1178.
(32) Chang, S.; Yoo, E.; Bae, I.; Cho, S.; Han, H. Org. Lett. 2006,
8, 1347.
(33) Typical Procedure for the Preparation of Compounds 6
The corresponding primary alkylamines 3 (1 mmol) and 4
(0.144 g, 1 mmol) were dissolved in MeCN (2 mL) and
stirred for 30 min. Then, a mixture of the sulfonyl azide 2,
(1.2 mmol), alkyne 1 (1 mmol), CuI (0.019, 0.1 mmol), and
Et3N (0.100 g, 1 mmol) in MeCN (3 mL) was slowly added
to the first mixture and was stirred at r.t. under N2
atmosphere. After completion of the reaction [about 8 h;
TLC (EtOAc–hexane = 1:5) monitoring], the mixture was
diluted with CH2Cl2 (2 mL) and aq NH4Cl solution (3 mL),
stirred for 30 min, and the layers were separated. The
aqueous layer was extracted with CH2Cl2 (3 × 3 mL), and the
combined organic fractions were dried (Na2SO4) and
concentrated under reduced pressure. The residue was
purified by flash column chromatography [silica gel (230–
400 mesh; Merck), hexane–EtOAc = 5:1] to give the
product.
NMR (125.7 MHz, CDCl3): δ = 31.5 (Me), 43.0 (CH2), 47.0
(CH2), 90.5 (CCl3), 122.5 (C), 128.8 (2 CH), 129.2 (CH),
129.3 (2 CH), 129.4 (2 CH), 130.0 (C), 132.5 (2 CH), 134.4
(CH), 171.7 (C), 176.0 (C). MS: m/z (%) = 445 (2) [M+], 366
(6), 353 (10), 351 (18), 203 (16), 94 (100), 91 (23), 78 (42),
77 (50). Anal. Calcd (%) for C18H18Cl3N3O2S (445.02): C,
48.39; H, 4.06; N, 9.41. Found: C, 48.72; H, 4.15; N, 9.32.
2,2,2-Trichloro-N′-(4-chlorobenzyl)-N-[1-(4-methylphenyl-
sulfonamido)-2-phenylethylidene]acetimidamide (6d)
Cream powder; mp 169–172 °C; yield 0.43 g (78%). IR
(KBr): νmax = 3039, 1633, 1590, 1368, 1218, 1018, 750 cm–
1. 1H NMR (500 MHz, CDCl3): δ = 2.46 (3 H, s, Me), 4.18
(2 H, s, CH2), 4.40 (2 H, s, CH2), 7.26–7.34 (3 H, m, Ph),
7.38 (2 H, d, 3J = 7.9 Hz, Ar), 7.43–7.47 (4 H, m, Ph), 7.88–
7.91 (4 H, m, Ph), 10.09 (1 H, s, NH). 13C NMR (125.7 MHz,
CDCl3): δ = 31.0 (Me), 42.4 (CH2), 46.2 (CH2), 90.4 (CCl3),
122.5 (C), 127.4 (2 CH), 128.7 (2 CH), 129.2 (C), 129.6 (2
CH), 130.7 (2 CH), 130.8 (2 CH), 132.5 (2 CH), 132.7 (CH),
140.9 (C), 142.1 (C), 147.3 (C), 170.6 (C), 176.0 (C). MS:
m/z (%) = 555 (2) [M+], 463 (7), 468 (20), 438 (16), 384 (23),
155 (100), 125 (22), 91 (70), 77 (50). Anal. Calcd (%) for
C24H21Cl4N3O2S (555.01): C, 51.72; H, 3.80; N, 7.54.
Found: C, 51.29; H, 3.71; N, 7.66.
2,2,2-Trichloro-N′-(4-chlorobenzyl)-N-[2-phenyl-1-
(phenylsulfonamido)ethylidene]acetimidamide (6e)
Cream powder; mp 149–152 °C; yield 0.39 g (73%). IR
(KBr): νmax = 3066, 1680, 1582, 1451, 1377, 1265, 1180,
1078, 758 cm–1. 1H NMR (500 MHz, CDCl3): δ = 4.08 (2 H,
s, CH2), 4.40 (2 H, s, CH2), 7.26–7.33 (3 H, m, Ph), 7.43 (2
H, d, 3J = 7.8 Hz, Ar), 7.46 (2 H, d, 3J = 7.9 Hz, Ar), 7.59 (2
H, t, 3J = 7.8 Hz, Ar), 7.71 (1 H, t, 3J = 7.9 Hz, Ar), 7.91 (2
H, d, 3J = 8.0 Hz, Ar), 8.02 (2 H, d, 3J = 8.0 Hz, Ar), 10.29
(1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 41.0 (CH2),
46.6 (CH2), 90.5 (CCl3), 122.6 (C), 127.4 (2 CH), 128.8 (2
CH), 129.2 (CH), 129.6 (2 CH), 130.1 (2 CH), 130.8 (2 CH),
132.6 (2 CH), 132.7 (C), 135.7 (CH), 140.9 (C), 144.8 (C),
170.6 (C), 176.0 (C). MS: m/z (%) = 541 (2) [M+], 463 (17),
449 (20), 399 (34), 384 (37), 141 (100), 125 (23), 91 (71), 77
(53). Anal. Calcd (%) for C23H19Cl4N3O2S (541.00): C,
50.85; H, 3.52; N, 7.73. Found: C, 51.29; H, 3.45; N, 7.66.
2,2,2-Trichloro-N′-(4-chlorobenzyl)-N-[1-(methyl-
sulfonamido)-2-phenylethylidene]acetimidamide (6f)
Cream powder; mp 179–182 °C; yield 0.33 g (70%). IR
(KBr): νmax = 3063, 1685, 1589, 1449, 1376, 1275, 1181,
1079, 748 cm–1. 1H NMR (500 MHz, CDCl3): δ = 3.65 (3 H,
s, Me), 4.07 (2 H, s, CH2), 4.40 (2 H, s, CH2), 7.26–7.34 (3
H, m, Ph), 7.43–7.48 (4 H, m, Ph), 7.90 (2 H, d, 3J = 8.0 Hz,
Ar), 10.10 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ =
31.0 (Me), 42.0 (CH2), 46.7 (CH2), 90.4 (CCl3), 122.5 (C),
128.8 (2 CH), 129.3 (CH), 129.7 (2 CH), 130.8 (2 CH),
132.5 (2 CH), 132.7 (C), 140.9 (C), 170.7 (C), 176.0 (C).
MS: m/z (%) = 478 (2) [M+], 399 (7), 387 (20), 353 (23), 267
(20), 125 (25), 94 (100), 91 (70), 79 (50), 77 (26). Anal.
Calcd (%) for C18H17Cl4N3O2S (478.98): C, 44.93; H, 3.56;
N, 8.73. Found: C, 44.39; H, 3.47; N, 8.79.
N′-Benzyl-2,2,2-trichloro-N-[1-(4-methylphenyl-
sulfonamido)-2-phenylethylidene]acetimidamide (6a)
Cream powder; mp 156–159 °C; yield 0.44 g (84%). IR
(KBr): νmax = 3060, 1687, 1592, 1448, 1375, 1178, 1079, 756
cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.47 (3 H, s, Me),
4.25 (2 H, s, CH2), 4.45 (2 H, s, CH2), 7.26–7.32 (3 H, m,
Ph), 7.38 (2 H, d, 3J = 7.4 Hz, Ar), 7.46–7.48 (4 H, m, Ph),
7.58 (1 H, t, 3J = 7.4 Hz, Ar), 7.89 (2 H, d, 3J = 7.9 Hz, Ar),
7.97 (2 H, d, 3J = 7.9 Hz, Ar), 10.08 (1 H, s, NH). 13C NMR
(125.7 MHz, CDCl3): δ = 31.5 (Me), 42.2 (CH2), 46.4 (CH2),
90.4 (CCl3), 122.6 (C), 127.5 (2 CH), 128.8 (2 CH), 129.2
(C), 129.3 (2 CH), 129.4 (2 CH), 130.8 (2 CH), 131.0 (CH),
132.5 (2 CH), 134.4 (CH), 142.1 (C), 147.3 (C), 171.7 (C),
176.0 (C). MS: m/z (%) = 521 (2) [M+], 430 (10), 404 (13),
366 (16), 170 (32), 155 (100), 91 (70), 77 (54). Anal. Calcd
(%) for C24H22Cl3N3O2S (521.05): C, 55.13; H, 4.24; N,
8.04. Found: C, 55.49; H, 4.30; N, 8.11.
N′-Benzyl-2,2,2-trichloro-N-[2-phenyl-1-
(phenylsulfonamido)ethylidene]acetimidamide (6b)
Cream powder; mp 160–163 °C; yield 0.40 g (80%). IR
(KBr): νmax = 3063, 1684, 1590, 1448, 1376, 1273, 1181,
1079, 759 cm–1. 1H NMR (500 MHz, CDCl3): δ = 4.18 (2 H,
s, CH2), 4.46 (2 H, s, CH2), 7.25–7.32 (3 H, m, Ph), 7.46–
7.49 (4 H, m, Ph), 7.58–7.61 (3 H, m, Ph), 7.71 (1 H, t, 3J =
7.4 Hz, Ar), 7.96 (2 H, d, 3J = 7.9 Hz, Ar), 8.03 (2 H, d, 3J =
7.9 Hz, Ar), 10.68 (1 H, s, NH). 13C NMR (125.7 MHz,
CDCl3): δ = 41.5 (CH2), 45.6 (CH2), 90.4 (CCl3), 122.6 (C),
127.4 (2 CH), 128.8 (2 CH), 129.2 (C), 129.3 (2 CH), 129.4
(2 CH), 130.2 (2 CH), 132.6 (2 CH), 134.2 (CH), 134.4
(CH), 135.7 (CH), 144.8 (C), 171.7 (C), 176.0 (C). MS: m/z
(%) = 507 (1) [M+], 415 (6), 390 (10), 351 (18), 273 (16),
141 (100), 91 (38), 77 (50). Anal. Calcd (%) for
C23H20Cl3N3O2S (507.03): C, 54.29; H, 3.96; N, 8.26.
Found: C, 54.61; H, 3.85; N, 8.34.
N′-Benzyl-2,2,2-trichloro-N-[1-(methylsulfonamido)-2-
phenylethylidene]acetimidamide (6c)
Cream powder; mp 142–145 °C; yield 0.33 g (74%). IR
(KBr): νmax = 3030, 1687, 1593, 1448, 1369, 1279, 1176,
1071, 751 cm–1. 1H NMR (500 MHz, CDCl3): δ = 3.64 (3 H,
s, Me), 4.12 (2 H, s, CH2), 4.45 (2 H, s, CH2), 7.25–7.33 (3
2,2,2-Trichloro-N′-(4-methylbenzyl)-N-[1-(4-methylphenyl-
sulfonamido)-2-phenylethylidene]acetimidamide (6g)
Cream powder; mp 189–193 °C; yield 0.43 g (81%). IR
(KBr): νmax = 3032, 1617, 1592, 1450, 1375, 1222, 1177,
1079, 749 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.43 (3 H,
s, Me), 2.68 (3 H, s, Me), 4.02 (2 H, s, CH2), 4.52 (2 H, s,
CH2), 7.29–7.34 (5 H, m, Ph), 7.40 (2 H, d, 3J = 7.8 Hz, Ar),
7.51 (2 H, d, 3J = 7.8 Hz, Ar), 7.79 (2 H, d, 3J = 7.8 Hz, Ar),
7.93 (2 H, d, 3J = 7.9 Hz, Ar), 10.09 (1 H, s, NH). 13C NMR
(125.7 MHz, CDCl3): δ = 32.0 (Me), 35.2 (Me), 41.9 (CH2),
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 161–164

164
I. Yavari et al.
LETTER
45.6 (CH2), 90.4 (CCl3), 122.6 (C), 127.4 (2 CH), 128.7 (2
CH), 129.2 (CH), 130.1 (2 CH), 130.3 (2 CH), 130.7 (2 CH),
132.5 (2 CH), 134.7 (C), 142.1 (C), 146.0 (C), 147.3 (C),
172.4 (C), 176.0 (C). MS: m/z (%) = 535 (1) [M+], 444 (7),
430 (23), 380 (20), 287 (42), 170 (54), 155 (100), 105 (22),
91 (70), 77 (40). Anal. Calcd (%) for C25H24Cl3N3O2S
(535.07): C, 55.93; H, 4.51; N, 7.83. Found: C, 56.35; H,
4.60; N, 7.76.
13.8 (Me), 20.8 (CH2), 22.3 (CH2), 37.7 (CH2), 45.5 (CH2),
90.4 (CCl3), 127.4 (2 CH), 129.6 (2 CH), 130.1 (2 CH),
130.8 (2 CH), 132.7 (C), 135.7 (CH), 141.0 (C), 144.8 (C),
170.6 (C), 176.0 (C). MS: m/z (%) = 507 (1) [M+], 449 (7),
382 (20), 366 (27), 155 (100), 141 (34), 125 (22), 91 (70), 77
(30), 57 (21). Anal. Calcd (%) for C20H21Cl4N3O2S (507.01):
C, 47.17; H, 4.16; N, 8.25. Found: C, 47.49; H, 4.27; N, 8.36.
N′-1-[(Benzylimino)-2,2,2-trichloroethyl]-N-
2,2,2-Trichloro-N′-(4-methylbenzyl)-N-[2-phenyl-1-
(phenylsulfonamido)ethylidene]acetimidamide (6h)
Cream powder; mp 179–182 °C; yield 0.41 g (78%). IR
(KBr): νmax = 3031, 1613, 1592, 1451, 1376, 1220, 1177,
1079, 743 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.45 (3 H,
s, Me), 4.02 (2 H, s, CH2), 4.72 (2 H, s, CH2), 7.31–7.37 (5
H, m, Ph), 7.51 (2 H, d, 3J = 7.8 Hz, Ar), 7.63 (2 H, t, 3J =
7.8 Hz, Ar), 7.67 (1 H, t, 3J = 7.8 Hz, Ar), 7.77 (2 H, d, 3J =
7.9 Hz, Ar), 8.07 (2 H, d, 3J = 7.9 Hz, Ar), 9.98 (1 H, s, NH).
13C NMR (125.7 MHz, CDCl3): δ = 32.3 (Me), 42.3 (CH2),
48.3 (CH2), 90.5 (CCl3), 122.6 (C), 127.4 (2 CH), 128.8 (2
CH), 129.3 (CH), 130.2 (2 CH), 130.3 (2 CH), 130.7 (2 CH),
132.6 (2 CH), 134.6 (C), 135.7 (CH), 144.8 (C), 146.0 (C),
172.4 (C), 176.4 (C). MS: m/z (%) = 521 (1) [M+], 430 (7),
415 (20), 380 (23), 273 (25), 141 (100), 91 (72), 77 (52).
Anal. Calcd (%) for C24H22Cl3N3O2S (521.05): C, 55.13; H,
4.24; N, 8.04. Found: C, 55.61; H, 4.35; N, 8.16.
tosylhexanimidamide (6k)
Pale yellow oil; yield: 0.30 g (60%). IR (KBr): νmax = 3032,
1685, 1592, 1372, 1278, 1187, 1072, 739 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.93 (3 H, t, 3J = 6.8 Hz, Me), 1.41–
1.48 (2 H, m, CH2), 1.50–1.55 (2 H, m, CH2), 1.93–1.96 (2
H, m, CH2), 2.50 (3 H, s, Me), 3.22 (2 H, t, 3J = 6.8 Hz, CH2),
4.48 (2 H, s, CH2), 7.41 (2 H, d, 3J = 7.8 Hz, Ar), 7.50 (2 H,
t, 3J = 7.8 Hz, Ar), 7.62 (1 H, t, 3J = 7.8 Hz, Ar), 7.92 (2 H,
d, 3J = 7.9 Hz, Ar), 7.99 (2 H, d, 3J = 7.9 Hz, Ar), 10.10 (1
H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 14.0 (Me),
18.5 (CH2), 22.2 (CH2), 24.4 (CH2), 31.0 (Me), 39.9 (CH2),
46.0 (CH2), 90.4 (CCl3), 122.5 (C), 127.4 (2 CH), 129.2 (2
CH), 129.4 (2 CH), 130.7 (2 CH), 134.4 (CH), 142.1 (C),
147.3 (C), 171.6 (C), 176.0 (C). MS: m/z (%) = 501 (1) [M+],
430 (7), 410 (20), 346 (42), 170 (32), 155 (100), 91 (25), 71
(50). Anal. Calcd (%) for C22H26Cl3N3O2S (501.08): C,
52.54; H, 5.21; N, 8.36. Found: C, 52.29; H, 5.30; N, 8.42.
N′-1-[(Benzylimino)-2,2,2-trichloroethyl]-N-
N′-1-(Benzylimino)-2,2,2-trichloroethyl)-N-tosyl-
pentanimidamide (6i)
(methylsulfonyl)hexanimidamide (6l)
Pale yellow oil; yield 0.34 g (69%). IR (KBr): νmax = 3030,
1679, 1582, 1451, 1376, 1179, 1078, 741 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.98 (3 H, t, 3J = 6.8 Hz, Me), 1.52–
1.59 (2 H, m, CH2), 1.95–1.97 (2 H, m, CH2), 2.50 (3 H, s,
Me), 3.21 (2 H, t, 3J = 6.8 Hz, CH2), 4.47 (2 H, s, CH2), 7.40
(2 H, d, 3J = 7.8 Hz, Ar), 7.51 (2 H, t, 3J = 7.8 Hz, Ar), 7.61
(1 H, t, 3J = 7.8 Hz, Ar), 7.91 (2 H, d, 3J = 7.9 Hz, Ar), 7.99
(2 H, d, 3J = 7.9 Hz, Ar), 10.09 (1 H, s, NH). 13C NMR (125.7
MHz, CDCl3): δ = 13.8 (Me), 20.8 (CH2), 22.2 (CH2), 31.4
(Me), 38.4 (CH2), 45.4 (CH2), 90.4 (CCl3), 122.5 (C), 127.4
(2 CH), 129.3 (CH), 129.4 (2 CH), 130.7 (2 CH), 134.4 (2
CH), 142.1 (C), 147.3 (C), 171.6 (C), 176.0 (C). MS: m/z
(%) = 487 (1) [M+], 430 (7), 396 (20), 370 (29), 170 (23),
155 (100), 91 (60), 77 (47), 57 (35). Anal. Calcd (%) for
C21H24Cl3N3O2S (487.07): C, 51.59; H, 4.95; N, 8.60.
Found: C, 51.18; H, 5.06; N, 8.74.
Pale yellow oil; yield: 0.24 g (57%). IR (KBr): νmax = 3030,
1679, 1451, 1376, 1265, 1179, 1078, 742 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.93 (3 H, t, 3J = 6.8 Hz, Me), 1.42–
1.49 (2 H, m, CH2), 1.51–1.55 (2 H, m, CH2), 1.94–1.96 (2
H, m, CH2), 3.24 (2 H, t, 3J = 6.8 Hz, CH2), 3.63 (3 H, s, Me),
4.48 (2 H, s, CH2), 7.50 (2 H, t, 3J = 7.7 Hz, Ar), 7.61 (1 H,
t, 3J = 7.7 Hz, Ar), 7.99 (2 H, d, 3J = 7.7 Hz, Ar), 10.08 (1 H,
s, NH). 13C NMR (125.7 MHz, CDCl3): δ = 13.9 (Me), 18.5
(CH2), 22.3 (CH2), 25.4 (CH2), 31.5 (Me), 39.9 (CH2), 46.1
(CH2), 90.4 (CCl3), 122.5 (C), 129.3 (2 CH), 129.4 (2 CH),
134.4 (CH), 171.7 (C), 176.0 (C). MS: m/z (%) = 425 (1)
[M+], 353 (7), 346 (20), 334 (34), 308 (21), 94 (100), 91 (28),
78 (65), 71 (50). Anal. Calcd (%) for C16H22Cl3N3O2S
(425.05): C, 45.03; H, 5.20; N, 9.85. Found: C, 45.49; H,
5.29; N, 9.76.
(34) Recently, Sharpless and co-workers established anhydrous
conditions with CuI in CHCl3–2,6-lutidine at 0 °C to prevent
intermediate 8 from decomposing and provide selective
formation of the desired 1-sulfonyltriazoles. See: Yoo, E. J.;
Ahlquist, M.; Kim, S. H.; Bae, I.; Fokin, V. V.; Sharpless, K.
B.; Chang, S. Angew. Chem. Int. Ed. 2007, 46, 1730.
(35) Cassidy, M. P.; Raushel, J.; Fokin, V. V. Angew. Chem. Int.
Ed. 2006, 45, 3154.
N-(Phenylsulfonyl)-N′-2,2,2-trichloro-1-[(4-
chlorobenzyl)imino)ethyl]pentanimidamide (6j)
Pale yellow oil; yield 0.32 g (64%). IR (KBr): νmax = 3031,
1610, 1494, 1368, 1224, 1173, 1070, 740 cm–1. 1H NMR
(500 MHz, CDCl3): δ = 0.99 (3 H, t, 3J = 6.8 Hz, Me), 1.52–
1.59 (2 H, m, CH2), 1.94–1.97 (2 H, m, CH2), 3.23 (2 H, t, 3J
= 6.8 Hz, CH2), 4.43 (2 H, s, CH2), 7.47 (2 H, d, 3J = 7.8 Hz,
Ar), 7.63 (2 H, t, 3J = 7.8 Hz, Ar), 7.76 (1 H, t, 3J = 7.8 Hz,
Ar), 7.92 (2 H, d, 3J = 7.9 Hz, Ar), 8.06 (2 H, d, 3J = 7.9 Hz,
Ar), 10.10 (1 H, s, NH). 13C NMR (125.7 MHz, CDCl3): δ =
(36) Yoo, E. J.; Ahlquist, M.; Bae, I.; Sharpless, K. B.; Fokin, V.
V.; Chang, S. J. Org. Chem. 2008, 73, 5520.
Synlett 2013, 24, 161–164
© Georg Thieme Verlag Stuttgart · New York