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Journal ArticleDOI

Synthesis of Functionalized N-Sulfonylamidines from N-Sulfonylketenimines and 2-Aminobenzimidazole

06 Mar 2015-Synthetic Communications (Taylor & Francis)-Vol. 45, Iss: 9, pp 1089-1093

AbstractThe synthesis of a novel class of N-(1H-benzo[d]imidazol-2-yl)-2-alkyl-N′-sulfonylacetamidines via a copper-catalyzed, three-component coupling reaction of 1H-benzo[d]imidazol-2-amine, sulfonyl azides, and terminal alkynes is described.

Topics: Tosyl azide (60%), Sulfonyl (56%), Coupling reaction (52%)

Summary (1 min read)

General Procedure for the Preparation of Compounds 5

  • The mixture was stirred at room temperature.
  • The residue was purified by flash column chromatography Merck) , AcOEt/hexane 1:3] to give product.

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1
Supplementary data for manuscript
SYNTHESIS OF FUNCTIONALIZED N-SULFONYLAMIDINES FROM
N-SULFONYLKETENIMINES AND 2-AMINOBENZIMIDAZOLE
Issa Yavari, Azam Sheikhi, Manijeh Nematpour, and Zohreh Taheri
Department of Chemistry, Tarbiat Modares University, Tehran, Iran
GRAPHICAL ABSTRACT
Abstract The synthesis of a novel class of N-(1H-benzo[d]imidazol-2-yl)-2-alkyl-N'-
sulfonylacetamidines via a copper-catalyzed three-component coupling reaction of 1H-
benzo[d]imidazol-2-amine, sulfonyl azides and terminal alkynes is described.
Keywords Amidines; copper iodide; N-sulfonylketenimines; tosyl azide; terminal alkyne
Address correspondence to Issa Yavari, Department of Chemistry, Tarbiat Modares
University, PO Box 14115-175, Tehran, Iran. E-mail: yavarisa@modares.ac.ir

2
EXPERIMENTAL
All chemicals were obtained commercially and used without further purification. M.p.:
Electrothermal-9100 apparatus. IR Spectra: Shimadzu-IR-460 spectrometer; bond positions in
cm
−1
.
1
H- and
13
C-NMR Spectra: Bruker DRX-500 Avance instrument at 400.1 and 100.6 MHz,
resp.; δ in ppm, J in Hz. MS: Finnigan-MAT-8430EI-MS mass spectrometer; at 70 eV; in m/z
(rel. %). Elemental analyses: Vario EL III CHNOS elemental analyzer.
General Procedure for the Preparation of Compounds 5
To a mixture of alkyne 1 (1 mmol), sulfonyl azide 2 (1.2 mmol), CuI (0.1 mmol), and
Et
3
N (1 mmol) in DMF (3 mL) was slowly added 2-amino-benzoimidazole (1.5 mmol). The
mixture was stirred at room temperature. After completion of the reaction [about 8 h; TLC
(AcOEt/hexane 1:3) monitoring], the mixture was diluted with CH
2
Cl
2
(2 mL) and aqueous
NH
4
Cl solution (3 mL), stirred for 30 min, and the layers were separated. The aqueous layer was
extracted with CH
2
Cl
2
(3 mL
×
3) and the combined organic fractions were dried (Na
2
SO
4
) and
concentrated under reduced pressure. The residue was purified by flash column chromatography
[silica gel (230-400 mesh; Merck), AcOEt/hexane 1:3] to give product.
N-(1H-benzo[d]imidazol-2-yl)-2-phenyl-N'-tosylacetamidine 5. Yield: 0.32 g (80%);
cream powder; m.p. = 156-159 °C. IR (KBr): 3160 (NH), 3030 (NH), 1448 (C=N), 1375 (SO
2
),
1178 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 2.48 (3H, s, Me), 4.25 (2H, s, CH
2
), 7.29-7.35
(3H, m, Ph), 7.40 (2H, d,
3
J
HH
= 7.9 Hz, Ar), 7.48 (2 H, d,
3
J
HH
= 7.5 Hz, Ar), 7.57 (1 H, t,
3
J
HH
=
7.4 Hz, Ar), 7.62 (1 H, t,
3
J
HH
= 7.4 Hz, Ar), 7.91 (2 H, d,
3
J
HH
= 7.9 Hz, Ar), 8.02 (1 H, d,
3
J
HH
=
7.4 Hz, Ar), 8.26 (1 H, d,
3
J
HH
= 7.4 Hz, Ar), 9.59 (1 H, s, NH), 10.48 (1 H, s, NH).
13
C NMR
(100.6 MHz, CDCl
3
): δ
C
= 30.8 (Me), 47.6 (CH
2
), 123.3 (CH), 123.6 (CH), 127.2 (C), 127.9 (CH),
128.2 (2 CH), 128.6 (CH), 129.5 (2 CH), 130.2 (CH), 130.8 (C), 131.4 (2 CH), 133.8 (2 CH), 141.7

3
(C), 142.8 (C), 148.2 (C), 158.1 (C), 166.0 (C). MS (EI, 70 eV): m/z (%) = 404 (M
+
, 5), 328 (10),
313 (13), 287 (16), 249 (32), 155 (100), 91 (70), 77 (54). Anal. calcd. for C
22
H
20
N
4
O
2
S (404.13): C,
65.33; H, 4.98; N, 13.85%. Found: C, 65.69; H, 5.02; N, 13.94%.
N-(1H-benzo[d]imidazol-2-yl)-2-phenyl-N'-(phenylsulfonyl)acetimidamide 5b.
Yield: 0.32 g (82%); cream powder; m.p. = 132-134 °C. IR (KBr): 3137 (NH), 3003 (NH), 1448
(C=N), 1376 (SO
2
), 1181 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 4.28 (2H, s, CH
2
), 7.30-
7.37 (3H, m, Ph), 7.49 (2H, d,
3
J
HH
= 7.8 Hz, Ar), 7.59 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 7.66-7.74 (3H, m,
Ph), 7.77 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 8.00-8.06 (3H, m, Ph), 8.29 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 9.72
(1H, s, NH), 10.88 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
= 46.9 (CH
2
), 122.9 (CH), 123.7
(CH), 127.3 (CH), 128.0 (2 CH), 128.2 (CH), 128.7 (CH), 129.2 (2 CH), 130.3 (CH), 130.7 (2 CH),
133.6 (2 CH), 134.5 (C), 136.4 (C), 145.6 (C), 148.7 (C), 158.7 (C), 167.1 (C). MS (EI, 70 eV): m/z
(%) = 390 (M
+
, 1), 313 (6), 299 (10), 273 (18), 249 (16), 141 (100), 132 (21), 91 (38), 77 (50), 78
(31). Anal. calcd. for C
21
H
18
N
4
O
2
S (390.12): C, 64.60; H, 4.65; N, 14.35%. Found: C, 64.93; H,
4.69; N, 14.42%.
N-(1H-benzo[d]imidazol-2-yl)-N'-(methylsulfonyl)-2-phenylacetimidamide 5c.
Yield 0.24 g (74%); cream powder, m.p. = 122-124 °C. IR (KBr): 3324 (NH), 3010 (NH), 1448
(C=N), 1369 (SO
2
), 1176 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 3.68 (3H, s, Me), 4.35
(2H, s, CH
2
), 7.31-7.35 (3H, m, Ph), 7.50 (2H, d,
3
J
HH
= 7.8 Hz, Ar), 7.60 (1H, t,
3
J
HH
= 7.5 Hz,
Ar), 7.66 (1H, t,
3
J
HH
= 7.7 Hz, Ar), 8.05 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 8.32 (1H, d,
3
J
HH
= 7.5 Hz,
Ar), 9.77 (1H, s, NH), 10.89 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
= 30.8 (Me), 46.0
(CH
2
), 122.6 (CH), 123.2 (C), 123.9 (CH), 128.4 (CH), 129.2 (CH), 129.4 (2 CH), 130.0 (CH),
133.2 (2 CH), 133.4 (C), 147.9 (C), 159.2 (C), 165.0 (C). MS (EI, 70 eV): m/z (%) = 328 (M
+
, 5),

4
252 (6), 273 (10), 211 (18), 196 (16), 91 (23), 78 (100), 77 (50). Anal. calcd. for C
16
H
16
N
4
O
2
S
(328.10): C, 58.52; H, 4.91; N, 17.06%. Found: C, 58.21; H, 4.95; N, 17.17%.
N-(1H-benzo[d]imidazol-2-yl)-N'-tosylhexanamidine 5d. Yield 0.24 g, (62%);
cream powder, mp: 111-113 °C, IR (KBr): 3224 (NH), 3039 (NH), 1490 (C=N), 1368 (SO
2
),
1179 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 0.92 (3H, t,
3
J
HH
= 6.9 Hz, Me), 1.39-1.45
(2H, m, CH
2
), 1.48-1.54 (2H, m, CH
2
), 2.17-2.21 (2H, m, CH
2
), 2.49 (3H, s, Me), 3.24 (2H, t,
3
J
HH
= 6.9 Hz, CH
2
), 7.41 (2H, d,
3
J
HH
= 7.9 Hz, Ar), 7.64 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 7.72 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 7.91 (2H, d,
3
J
HH
= 7.9 Hz, Ar), 8.08 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 8.37 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 9.39 (1H, s, NH), 10.98 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
=
14.7 (Me), 19.2 (CH
2
), 22.5 (CH
2
), 22.9 (CH
2
), 30.8 (Me), 31.6 (CH
2
), 127.2 (CH), 128.1 (2
CH), 128.8 (CH), 129.7 (CH), 130.9 (CH), 131.4 (2 CH), 141.8 (C), 142.7 (C), 145.8 (C), 148.0
(C), 160.7 (C), 164.9 (C). MS (EI, 70 eV): m/z (%) = 384 (M
+
, 5), 313 (7), 293 (20), 229 (16),
155 (100), 91 (74), 77 (30), 76 (32), 71 (54). Anal. calcd. for C
20
H
24
N
4
O
2
S (384.16): C, 62.48;
H, 6.29; N, 14.57%. Found: C, 62.69; H, 6.33; N, 14.66%.
N-(1H-benzo[d]imidazol-2-yl)-N'-(phenylsulfonyl)hexanimidamide 5e. Yield
0.21 g (57%); cream powder, m.p. = 119-122 °C. IR (KBr): 3348 (NH), 3066 (NH), 1451 (C=N),
1377 (SO
2
), 1180 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 0.89 (3H, t,
3
J
HH
= 6.9 Hz, Me),
1.37-1.44 (2H, m, CH
2
), 1.46-1.54 (2H, m, CH
2
), 2.17-2.21 (2H, m, CH
2
), 3.39 (2H, t,
3
J
HH
= 6.9
Hz, CH
2
), 7.61 (2H, t,
3
J
HH
= 7.9 Hz, Ar), 7.70-7.78 (2H, m, Ph), 7.98 (1H, t,
3
J
HH
= 7.5 Hz, Ar),
8.06 (2H, d,
3
J
HH
= 7.9 Hz, Ar), 8.13 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 8.40 (1H, d,
3
J
HH
= 7.5 Hz, Ar),
9.51 (1H, s, NH), 10.33 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
= 14.7 (Me), 19.3
(CH
2
), 22.9 (CH
2
), 30.8 (CH
2
), 31.7 (CH
2
), 127.2 (2 CH), 128.5 (2 CH), 129.3 (CH), 129.6
(CH), 130.4 (CH), 131.7 (CH), 136.5 (C), 139.4 (CH), 144.0 (C), 145.4 (C), 162.0 (C), 166.8

5
(C). MS (EI, 70 eV): m/z (%) = 370 (M
+
, 7), 299 (17), 253 (20), 229 (34), 141 (100), 125 (23),
77 (41), 76 (33). Anal. calcd. for C
19
H
22
N
4
O
2
S (370.15): C, 61.60; H, 5.99; N, 15.12%. Found:
C, 61.21; H, 6.04; N, 15.21%.
N-(1H-benzo[d]imidazol-2-yl)-N'-(methylsulfonyl)hexanimidamide 5f. Yield
0.16 g (53%); cream powder, m.p. = 100-103 °C. IR (KBr): 3387 (NH), 3043 (NH), 1449 (C=N),
1376 (SO
2
), 1181 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 0.90 (3H, t,
3
J
HH
= 6.9 Hz, Me),
1.35-1.42 (2H, m, CH
2
), 1.44-1.50 (2H, m, CH
2
), 2.11-2.18 (2H, m, CH
2
), 3.10 (3H, s, Me), 3.37
(2H, t,
3
J
HH
= 6.9 Hz, CH
2
), 7.71 (1H, t,
3
J
HH
= 7.9 Hz, Ar), 7.78 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 8.10
(1H, d,
3
J
HH
= 7.9 Hz, Ar), 8.40 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 9.21 (1H, s, NH), 10.10 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
= 14.6 (Me), 19.2 (CH
2
), 23.0 (CH
2
), 30.7 (CH
2
), 31.6 (CH
2
),
33.0 (Me), 121.3 (CH), 124.4 (CH), 129.4 (CH), 130.4 (CH), 132.5 (C), 144.1 (C), 162.1 (C),
165.5 (C). MS (EI, 70 eV): m/z (%) = 308 (M
+
, 7), 237 (7), 229 (20), 191 (23), 176 (20), 78
(100), 77 (26). Anal. calcd. for C
14
H
20
N
4
O
2
S (308.13): C, 54.52; H, 6.54; N, 18.17%. Found: C,
54.27; H, 6.50; N, 18.26%.
N-(1H-benzo[d]imidazol-2-yl)-N'-tosylpentanimidamide 5g. Yield 0.24 g (65%);
cream powder, m.p. = 102-105 °C. IR (KBr): 3354 (NH), 3044 (NH), 1444 (C=N), 1306 (SO
2
),
1180 cm
-1
(SO
2
).
1
H NMR (400 MHz, CDCl
3
): δ
H
= 1.02 (3H, t,
3
J
HH
= 6.9 Hz, Me), 1.49-1.63
(2H, m, CH
2
), 1.78-1.92 (2H, m, CH
2
), 2.50 (3H, s, Me), 3.05 (2H, t,
3
J
HH
= 6.9 Hz, CH
2
), 7.41
(2H, d,
3
J
HH
= 7.9 Hz, Ar), 7.59 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 7.66 (1H, t,
3
J
HH
= 7.5 Hz, Ar), 7.93
(2H, d,
3
J
HH
= 7.9 Hz, Ar), 8.04 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 8.30 (1H, d,
3
J
HH
= 7.5 Hz, Ar), 8.62
(1H, s, NH), 9.64 (1H, s, NH).
13
C NMR (100.6 MHz, CDCl
3
): δ
C
= 14.5 (Me), 21.5 (CH
2
), 22.4
(CH
2
), 23.0 (Me), 24.8 (CH
2
), 123.8 (CH), 128.1 (2 CH), 128.4 (CH), 128.6 (CH), 128.7 (CH),
130.1 (2 CH), 141.8 (C), 142.9 (C), 144.7 (C), 147.8 (C), 148.0 (C), 159.1 (C). MS (EI, 70 eV):

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Abstract: The synthesis of a novel class of N-(1H-benzo[d]imidazol-2-yl)-2-alkyl-N′-sulfonylacetamidines via a copper-catalyzed, three-component coupling reaction of 1H-benzo[d]imidazol-2-amine, sulfonyl azides, and terminal alkynes is described.

References
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Journal ArticleDOI
Abstract: Amidines, R'NH—C(R)NR' , as for the isoelectronic carboxylic acids, form a large number of transition metal derivatives, the metals varying from early metals in high oxidation states to the later metals in lower oxidation states. Various bonding modes for the amidino group are involved, and are reviewed with reference to other aza-allyl systems. Much current interest arises from the ability of the ligand to bridge between metals, facilitating metal-metal bonding, and from the use of unsymmetrically substituted amidino groups to produce chiral complexes. Methods of synthesis are reviewed, together with infrared and NMR spectroscopic, mass spectrometric and thermal analysis data. The complexes are introduced systematically according to their Period Group, making easy access to information on specific metal complexes. Mixed-metal complexes containing amidino groups bridging between different metals are considered separately. X-ray crystallographic data is collated in a table, thus providing an accessible source for reference purposes. Source material for the review amounts to about 300 references.

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Journal ArticleDOI
Imhyuck Bae1, Hoon Han1, Sukbok Chang1
TL;DR: Two plausible mechanistic pathways involving ketenimine or triazole intermediate are tentatively presented for the copper-catalyzed three-component coupling reactions.
Abstract: A highly efficient, mild, practical, and catalytic multicomponent reaction for the synthesis of N-sulfonylamidines has been developed. This reaction has an extremely wide scope with regard to all three coupling components of alkyne, sulfonyl azide, and amine. Two plausible mechanistic pathways involving ketenimine or triazole intermediate are tentatively presented for the copper-catalyzed three-component coupling reactions.

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Abstract: (Chemical Equation Presented) 4-Substituted 1-(N-sulfonyl)-1,2,3-triazoles are selectively obtained by using the Cu-catalyzed azide-alkyne cycloaddition reaction with sulfonyl azides. Performing the reaction at 0°C in chloroform in the presence of 2,6-lutidine and Cul as the catalyst effectively prevents the ketenimine pathway and provides convenient access to N-sulfonyltriazoles in good to excellent yields.

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Book ChapterDOI
TL;DR: The interesting finding for the present chapter is that the NO is formed by nitric oxide synthetase from arginine—the only essential amino acid which carries a guanidine group.
Abstract: Publisher Summary This chapter focuses on amidines and guanidines in medicinal chemistry. The drugs are classified under their main physiological activities and within each group are arranged roughly in order of increasing molecular complexity. Many of the compounds have given temporary excitement to their discoverers and then been dropped—the commonest experience in medicinal chemistry. There are important, clinically used, medicines in all the major categories of therapeutic action discussed in the chapter. This simple and very unstable compound is not only a neurotransmitter in the brain, but acts in the dilation of blood vessels and activates leucocytes to attack tumour cells, fungi, and bacteria. In addition, nitric oxide can inhibit blood coagulation by preventing platelet aggregation and appears to be the regulator of the male erection. No doubt other functions will be discovered in the future, but the interesting finding for the present chapter is that the NO is formed by nitric oxide synthetase from arginine—the only essential amino acid which carries a guanidine group. Since most of the active guanidine drugs have at least one unsubstituted =NH or NH 2 group, it is interesting to speculate that they will be shown to act by giving nitric oxide as well.

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Frequently Asked Questions (1)
Q1. What have the authors contributed in "Synthesis of functionalized n-sulfonylamidines from n-sulfonylketenimines and 2-aminobenzimidazole" ?

In this paper, the synthesis of a novel class of N- ( 1H-benzo [ d ] imidazol-2-yl ) -2-alkyl-N'sulfonylacetamidines via a copper-catalyzed three-component coupling reaction of 1Hbenzo [ d ] IMIDazol 2-amine, sulfonyl azides and terminal alkynes is described.