Carbene-mediated transformations of 1-(benzylideneamino)benzimidazoles

Article abstract of DOI:10.1021/jo200088s

Carbene-mediated transformations of N-(3-butylbenzimidazol-3-ium-1-yl)-1- arylmethanimine iodides with carbon disulfide and benzoyl isothiocyanate gave the corresponding NHC·CS₂ betaines in 68-85% and benzoyl-[1-butyl-3-[(E)-(aryl)methyleneamin

Full text of DOI:10.1021/jo200088s

NOTE
pubs.acs.org/joc
Carbene-Mediated Transformations of
1-(Benzylideneamino)benzimidazoles
Alan R. Katritzky,*,‡ Davit Jishkariani,‡ Rajeev Sakhuja,‡ C. Dennis Hall,‡ and Peter J. Steel§
‡Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200, United States
§Chemistry Department, University of Canterbury, Christchurch, New Zealand *E-mail: katritzky@chem.ufl.edu.
S Supporting Information
b
ABSTRACT: Carbene-mediated transformations of N-(3-butyl-
benzimidazol-3-ium-1-yl)-1-arylmethanimine iodides with carbon
disulfide and benzoyl isothiocyanate gave the corresponding NHC
3
CS2 betaines in 68ꢀ85% and benzoyl-[1-butyl-3-[(E)-(aryl)-
methyleneamino]benzimidazol-1-ium-2-carbothioyl]azanides, res-
pectively, in 74ꢀ85% yields. However, reaction with excess isopropyl isothiocyanate in NaH/THF at room temperature yielded the
1-butyl-10,30-diisopropyl-3-[(E)-(aryl)methyleneamino]spiro[benzimidazole-2,50-imidazolidine]-20,40-dithiones (74ꢀ77%).
arbenes derived from nitrogen heterocycles (NHC) are
well-known organocataysts for benzoin condensations,1,2
1-Aminobenzimidazole (2) was synthesized from benzimida-
zole (1) and hydroxylamine-O-sulfonic acid in 75% yield following
a literature procedure.43 N-(Arylmethyleneimino)benzimidazoles
4aꢀf were synthesized in 69ꢀ94% yield by the reaction of 1-amino-
benzimidazole 2 with aldehydes 3aꢀf, in ethanol in the presence of a
catalytic quantity of sulfuric acid44 (Scheme 1, Table 1), Quaterniza-
tion of N-(arylmethyleneimino)benzimidazoles 4aꢀf with butyl
iodide 5 gave the corresponding 3-butyl-N-(arylmethyleneimino)-
benzimidazolium iodides 6aꢀf in quantitative yields (Scheme 1,
Table 1).
C
Stetter3,4 and Staudinger reactions,5 oxidative amidation,6 annu-
lation of enals,7 ring-opening polymerizations,8,9 transesterifica-
tions,10,11 and other transformations;12 they are also versatile ligands
for transition metals.13ꢀ15 The σ-donating ability and strong nucleo-
philic character of NHC offers opportunities for the construction of
substituted heterocycles16ꢀ21 and novel molecular frameworks.22,23
An important property of NHCs is the ability to react with
CO2,24ꢀ26 CS2,27ꢀ29 and isothiocyanates27,29 to form imidazol-
2-ylidene, 1,3-thiazol-2-ylidene,17,30 1,2,4-triazol-3-ylidene,17,31,32
and isothiazol-3-ylidene adducts.
Scheme 1
A wide range of stable benzimidazolium or imidazol(in)iumꢀ
CS2 adducts have been studied as novel ionic liquids,25,27,33 as
catalysts in the cyanosilylation of aldehydes,34 as intermediates for
sulfur heterocycles,35 ligands for gold complexes, surface units for
gold nanoparticles,36 and promising antifungal and antibacterial
agents.29,37
NHC zwitterionic betaine adducts with isothiocyanates
(NHC RNCS) are powerful intermediates for the synthesis of
3
a variety of heterocycles.38,39 Thus, Cheng and co-workers utilized
2-thiocarbamoyl benzimidazolium, imidazolium, and triazolium
zwitterionic inner salts in [3 þ 2] cycloaddition reactions, resulting
in spiro-heterocycles.38,39
Most literature NHC examples are based on imidazole and
benzimidazole nuclei bearing various alkyl or aryl groups on nitro-
gen. An early report by Balch described a template synthesis of an
N-amino-substituted N-heterocyclic carbene.40 Lassaletta described
the synthesis and application of a class of N-heterocyclic carbenes
based on bis(N,N-dialkylamino)imidazolin-2-ylidines.41,42
1,3-Dimethylbenzimidazolium iodide (7) was synthesized from
benzimidazole following a literature procedure.48 The singlet car-
bene generated in situ at the C-2 position of 1,3-dimethylbenzimi-
dazolium iodide 7 by treatment with sodium hydride, on reaction
with carbon disulfide 8, gave 1,3-dimethylbenzimidazol-3-ium-2-
carbodithioate (10) in 85% yield (Scheme 2). Deprotonation of
However, we found no literature reports of NHC CS2 or
3
NHC RNCS betaines or spirocyclic derivatives of N-(arylmethyl-
3
eneimino)benzimidazoles. Herein, we describe our results from
the carbene-mediated transformations of 1-(benzylideneamino)-
benzimidazoles.
Received: January 21, 2011
Published: April 11, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200088s J. Org. Chem. 2011, 76, 4082–4087
|

The Journal of Organic Chemistry
NOTE
Table 1. Synthesis of N-(Arylmethyleneimino)benzimidazoles
and Their Quaternized Salts
dazolium iodide (7) on reaction with excess of isopropyl isothio-
cyanate (11) in the presence of sodium hydride/THF at room
temperature gave (1,3-dimethylbenzimidazol-3-ium-2-carbothioyl)-
isopropylazanide (12) in 86% yield (Scheme 3).
products 4aꢀf
yield (%) mp (°C)
products 6aꢀf
entry
Ar
yield (%)
mp (°C)
Scheme 3
a
b
c
d
e
f
4-CH3OꢀC6H4
C6H5
4-Br-2-thiophenyl
4-CH3ꢀC6H4
4-NO2ꢀC6H4
4-Et2NꢀC6H4
92
94
69
82
79
91
93ꢀ95
100
100
100
100
100
100
154ꢀ155
171ꢀ172
175ꢀ176
167ꢀ169
217ꢀ219
151ꢀ152
125a
174ꢀ175
74ꢀ75
225ꢀ226b
118c
a Literature45 mp 125ꢀ126 °C. b Literature46 mp 223 °C. c Literature47
mp not available.
However, the reaction of N-(3-butylbenzimidazol-3-ium-1-yl)-
1-(aryl)methanimine iodides (6a,b) with excess of isopropyl
isothiocyanate 11 in the presence of NaH/THF at room tem-
perature led to the formation of red crystalline compounds (13a,b)
N-(3-butylbenzimidazol-3-ium-1-yl)-1-(aryl)methanimine iodides
6aꢀc using sodium hydride, followed by reaction with carbon
disulfide 8 at room temperature, formed the corresponding NHC
3
1
in 74ꢀ77% yield (Scheme 4, Table 3). The H and 13C NMR
CS2 betaines (9aꢀc) (68ꢀ76%) (Scheme 2, Table 2). Isolation of
the NHC CS2 betaine adducts was achieved by crystallization
3
spectra were complex and did not correspond to the formation of a
betaine intermediate (Scheme 4). In fact, the spectroscopic data
revealed two isopropyl groups, and the structure of representative
example 13a was confirmed by single-crystal X-ray diffraction
studies (Figure 1). The X-ray crystallographic data proved the
formation of 1-butyl-10,30-diisopropyl-3-[(E)-(aryl)methylene-
amino]spiro[benzimidazole-2,50-imidazolidine]-20,40-dithiones
(13a,b), resulting from the addition of a second molecule of
techniques in all cases. The structure of one representative example,
9a, was confirmed by single-crystal X-ray diffraction (Figure 1).
More interesting results were obtained when the reaction of
benzimidazolium salts with isopropyl isothiocyanate was carried out
under similar experimental conditions. 1,3-Dimethylbenzimi-
Scheme 2
isopropyl isothiocyanate to the NHC RNCS betaine adduct. In fact,
3
with an imine function in the side chain, we were unable to isolate
NHC RNCS betaine adducts because the corresponding adducts
3
reacted further with heteroallene even when the reagents were
present in stoichiometric (1:1) or substoichiometric quantities. This
result indicates that the intermolecular formation of 13a,bis preferred
over the intramolecular cyclization to 130a,b (Scheme 4). However,
in the case of 1,3-dimethylbenzimidazolium iodide 7, the reaction
Table 2. Synthesis of NHC CS2 Betaine Adducts
3
reactant product
R
R1 yield (%) mp (°C)
stopped at the NHC RNCS betaine step and no spirocyclic product
3
was observed even in presence of excess isopropyl isothiocyanate or
at elevated temperatures.
6a
6b
6c
7
9a
9b
9c
10
ꢀNdCH-(4-CH3OꢀC6H4) Bun
70
76
68
85
160ꢀ161
171ꢀ172
170ꢀ173
235ꢀ236a
ꢀNdCHꢀC6H5
Bun
ꢀNdCH-(4-Br-2-thiophenyl) Bun
Scheme 4
CH3
CH3
a Literature37 mp 237ꢀ238 °C.
Zwitterionic NHC RNCS betaine intermediates were only
3
isolated when a strongly deactivated isothiocyanate (benzoyl
isothiocyanate) was used. Thus the reaction of benzimidazolium
salts (6aꢀc, 7) with equivalent amounts of benzoyl
Figure 1. X-ray structures of 9a, 13a, and 16.
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The Journal of Organic Chemistry
NOTE
Table 3. Synthesis of Spiro[imidazolidine-4,20-indoline]-2,
5-dithiones
’ EXPERIMENTAL SECTION
Melting points were determined on a capillary point apparatus
equipped with a digital thermometer and are uncorrected. NMR spectra
were recorded in CDCl3 or DMSO-d6 with TMS for 1H (300 MHz) and
13C (75 MHz) as an internal reference. Aminating agent 17 was
prepared via a two-step literature procedure.50 Elemental analysis was
performed on a Carlo Erba-1106 instrument.
General Method for the Preparation of Imines 4aꢀf:
1-Aminobenzimidazole and corresponding aldehyde (1.05 equiv) were
dissolved in absolute ethanol and stirred in the presence of a catalytic amount
of sulfuric acid. After 5 h, the solvent was removed under reduced pressure
and the imines were obtained by recrystallization from EtOAc/hexanes.
N-(Benzimidazol-1-yl)-1-(4-methoxyphenyl)methanimine
(4a): White microcrystals (92%), mp 93ꢀ95.0 °C; 1H NMR (CDCl3) δ
8.69 (s, 1H), 8.32 (s, 1H), 7.85ꢀ7.78 (m, 3H), 7.75ꢀ7.70 (m, 1H),
7.39ꢀ7.28 (m, 2H), 7.02ꢀ6.97 (m, 2H), 3.87 (s, 3H); 13C NMR
(CDCl3) δ 162.5, 152.2, 142.5, 136.5, 131.9, 129.9, 125.6, 123.9, 123.0,
120.7, 114.5, 110.8, 55.5. Anal. Calcd for C15H13N3O: C, 71.70; H, 5.21;
N, 16.72. Found: C, 71.87; H, 5.28; N, 16.78.
reactant
product
Ar
yield (%)
mp (°C)
6a
6b
13a
13b
4-CH3OꢀC6H4
77
74
141ꢀ142
116ꢀ119
C6H5
isothiocyanate (14) in the presence of NaH/THF led to benzoyl
benzimidazolium-2-carbonothioyl)amides (15aꢀc, 16) in
74ꢀ85% yield (Scheme 5, Table 4). The structure of represen-
tative example 16 was confirmed by single-crystal X-ray diffrac-
tion studies (Figure 1).
Scheme 5
N-(Benzimidazol-1-yl)-1-phenyl-methanimine (4b): White
microcrystals (94%), mp 125.0 °C (lit.45 mp 125ꢀ126 °C); 1H NMR
(CDCl3) δ 8.76 (d, J = 2.7 Hz, 1H), 8.37 (s, 1H), 7.91ꢀ7.86 (m, 2H),
7.84ꢀ7.80 (m, 1H), 7.78ꢀ7.73 (m, 1H), 7.52ꢀ7.47 (m, 3H),
7.41ꢀ7.29 (m, 2H); 13C NMR (CDCl3) δ 151.7, 142.5, 136.6, 132.9,
131.8, 131.6, 129.0, 128.1, 124.1, 123.1, 120.7, 110.8. Anal. Calcd for
C14H11N3: C, 76.00; H, 5.01; N, 18.99. Found: C, 75.82; H, 4.99;
N, 19.07.
N-(Benzimidazol-1-yl)-1-(4-bromo-2-thienyl)methanimine
(4c): Colorless crystals (79%), mp 174.0ꢀ175.0 °C; 1H NMR (DMSO-d6)
δ 9.36 (s, 1H), 8.90 (s, 1H), 7.99 (s, 1H), 7.78 (d, J = 7.8 Hz, 1H), 7.74 (d,
J = 7.8 Hz, 1H), 7.69 (s, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.32 (t, J = 7.5 Hz,
1H); 13C NMR (DMSO-d6) δ 146.4, 141.6, 138.9, 137.4, 134.4, 131.4,
128.1, 123.8, 122.8, 119.9, 110.6, 109.6. Anal. Calcd for C12H8BrN3S: C,
47.07; H, 2.63; N, 13.72. Found: C, 47.12; H, 2.59; N, 13.60.
Table 4. Synthesis of NHC RNCS Betaine Adducts
3
reactant product
R
R1 yield (%) mp (°C)
6a
6b
6c
7
15a
15b
15c
16
ꢀNdCH-(4-CH3OꢀC6H4) Bun
83
77
74
85
126ꢀ128
125ꢀ127
151ꢀ154
207ꢀ210
ꢀNdCHꢀC6H5
Bun
ꢀNdCH-(4-Br-2-thiophenyl) Bun
CH3
CH3
In an extension of this work, we studied the influence of
functional groups on N-1 nitrogen, on the amination of 1-ami-
nobenzimidazole and its derivatives. Compounds 2 and 4aꢀf
were reacted with 2,4-dinitrophenyl hydroxylamine (17) to form
18 and 19aꢀf in 0ꢀ80% yield.49 We found that imines with
electron-donating substituents in the side chain gave higher
yields compared to those with electron-withdrawing groups,
and aminated products of some derivatives were not detected
at all (Scheme 6, Table 5).
N-(Benzimidazol-1-yl)-1-(p-tolyl)methanimine (4d): White
microcrystals (82%), mp 74ꢀ75.0 °C; 1H NMR (CDCl3) δ 8.71 (s, 1H),
8.38 (s, 1H), 7.83ꢀ7.72 (m, 4H), 7.39ꢀ7.25 (m, 4H), 2.42 (s, 3H); 13C
NMR (CDCl3) δ 152.4, 142.4, 142.3, 136.6, 131.9, 130.3, 129.8, 128.2,
124.1, 123.2, 120.7, 110.9, 21.7. Anal. Calcd for C15H13N3: C, 76.57; H, 5.57;
N, 17.86. Found: C, 76.67; H, 5.61; N, 17.99.
N-(Benzimidazol-1-yl)-1-(4-nitrophenyl)methanimine (4e):
Yellow microcrystals (79%), mp 225ꢀ226 °C (lit.46 mp 223 °C); 1H NMR
(DMSO-d6) δ9.36 (s, 1H), 9.03 (s, 1H), 8.40 (d, J= 7.8 Hz, 2H), 8.20 (d, J=
7.7 Hz, 2H), 7.90 (d, J = 7.8 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.5
Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H); 13C NMR (DMSO-d6) δ 150.1, 148.5,
141.7, 139.2, 137.1, 131.8, 128.8, 124.1, 123.0, 120.0, 110.8. Anal. Calcd for
C14H10N4O2: C, 63.15; H, 3.79; N, 21.04. Found: C, 63.03; H, 3.70; N, 20.79.
4-[(E)-Benzimidazol-1-yliminomethyl]-N,N-diethylaniline
(4f): Green crystals (91%), mp 118.0 °C (lit.47 mp not available); 1H NMR
(DMSO-d6) δ8.96 (s, 1H), 8.89 (s, 1H), 7.77ꢀ7.70(m4H), 7.35(t, J=7.4
Hz, 1H), 7.27 (t, J = 7.6 Hz 1H), 6.78 (d, J = 9.0 Hz, 2H), 3.42 (q, J = 7.0 Hz,
4H), 1.13 (t, J = 6.9 Hz, 6H); 13C NMR (DMSO-d6) δ 154.6, 149.9, 141.5,
136.5, 132.0, 130.0, 123.2, 122.1, 119.7, 119.1, 111.0, 110.5, 43.7, 12.3. Anal.
Calcd for C18H20N4: C, 73.94; H, 6.89; N, 19.16. Found: C, 73.56; H, 7.00;
N, 18.99.
Scheme 6
Table 5. Amination of 1-Aminobenzimidazole and Its Imine
Derivatives
General Method for the Preparation of N-(3-Butylbenzimi-
dazol-3-ium-1-yl)-1-arylmethanimine iodides (6aꢀf): 1-Iodo-
butane (3 equiv) and the corresponding imines 4aꢀf were heated with
stirring at 100 °C in a round-bottom flask for 5 h without solvent. Excess
1-iodobutane was removed under reduced pressure at 50 °C to give the
corresponding 3-butyl-N-(arylmethyleneimino)benzimidazolium iodides
6aꢀf in quantitative yields.
reactant product
R
yield (%)
mp (°C)
2
18
ꢀNH2
80
42
0
0
40
0
166ꢀ168
146ꢀ148
4a
4b
4c
4d
4e
4f
19a
19b
19c
19d
19e
19f
ꢀNdCH-(4-CH3OꢀC6H4)
ꢀNdCHꢀC6H5
ꢀNdCH-(4-Br-2-thiophenyl)
ꢀNdCH-(4-CH3ꢀC6H4)
ꢀNdCH-(4-NO2ꢀC6H4)
ꢀNdCH-(4-Et3NꢀC6H4)
132ꢀ134
N-(3-Butylbenzimidazol-3-ium-1-yl)-1-(4-methoxyphenyl)-
methanimine iodide (6a): White crystals (100%), mp 154.0ꢀ155.0 °C;
60
180
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NOTE
1H NMR (DMSO-d6) δ 10.57 (s, 1H), 9.38 (s, 1H), 8.23ꢀ8.20 (m, 1H),
8.13ꢀ8.09 (m, 1H), 8.02 (d, J = 8.8 Hz, 2H), 7.80ꢀ7.74 (m, 2H), 7.20 (d,
J = 8.8 Hz, 2H), 4.59 (t, J = 7.3 Hz, 2H), 3.90 (s, 3H), 2.03 (quintet, J = 7.4
Hz, 2H), 1.45 (sextet, J = 7.3 Hz, 2H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR
(DMSO-d6) δ 163.3, 162.1, 135.7, 131.3, 130.0, 129.4, 127.2, 126.9, 123.6,
114.9, 113.8, 113.1, 55.7, 47.1, 30.4, 19.1, 13.4. Anal. Calcd for C19H22IN3O:
C, 52.42; H, 5.09; N, 9.65. Found: C, 52.33; H, 5.15; N, 9.51.
pressure, and the residue was recrystallized from EtOH to obtain the
corresponding NHC CS2 betaines 9aꢀc, 10.
3
1-Butyl-3-[(E)-(4-methoxyphenyl)methyleneamino]ben-
zimidazol-1-ium-2-carbodithioate (9a): Red crystals (70%), mp
160.0ꢀ161.0 °C; 1H NMR (DMSO-d6) δ 9.25 (s, 1H), 8.06 (d, J = 8.4
Hz, 1H), 7.93ꢀ7.87 (m, 3H), 7.73ꢀ7.61 (m, 2H), 7.14 (d, J = 8.7 Hz, 2H),
4.44 (t, J = 7.7 Hz, 2H), 3.87 (s, 3H), 1.91 (quintet, J = 7.5 Hz, 2H), 1.38
(sextet, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C NMR (DMSO-d6) δ
222.6, 168.2, 163.5, 146.6, 131.4, 128.1, 127.3, 126.6, 123.6, 114.7, 113.5,
112.8, 55.7, 44.7, 30.4, 19.3, 13.4.
N-(3-Butylbenzimidazol-3-ium-1-yl)-1-phenylmethanimine
1
iodide (6b): White crystals (100%), mp 171.0ꢀ172.0 °C; H NMR
(DMSO-d6) δ 10.58 (s, 1H), 9.44 (s, 1H), 8.25ꢀ8.15 (m, 2H), 8.08 (d, J =
6.9 Hz, 2H), 7.82ꢀ7.76 (m, 2H), 7.74ꢀ7.64 (m, 3H), 4.59 (t, J = 7.2 Hz,
2H), 2.02 (quintet, J = 7.5 Hz, 2H), 1.45 (sextet, J = 7.5 Hz, 2H), 0.98 (t, J =
7.3 Hz, 3H); 13C NMR (DMSO-d6) δ 162.6, 136.0, 133.3, 131.2, 130.0,
129.4, 129.3, 129.1, 127.3, 127.0, 113.9, 113.1, 47.1, 30.4, 19.1, 13.4. Anal.
Calcd for C18H20IN3: C, 53.35; H, 4.97; N, 10.37. Found: C, 53.06; H, 4.95;
N, 10.18.
1-[(E)-Benzylideneamino]-3-butylbenzimidazol-3-ium-2-
1
carbodithioate (9b): Red crystals (76%), mp 171.0ꢀ172.0 °C; H
NMR (DMSO-d6) δ 9.38 (s, 1H), 8.09ꢀ8.05 (m, 1H), 8.00ꢀ7.92 (m,
3H), 7.74ꢀ7.65 (m, 3H), 7.64ꢀ7.56 (m, 2H), 4.45 (t, J = 7.7 Hz, 2H),
1.92 (quintet, J = 7.2 Hz, 2H), 1.39 (sextet, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4
Hz, 3H); 13C NMR (DMSO-d6) δ 222.5, 168.2, 146.6, 133.5, 131.3,
129.2, 129.1, 128.2, 127.2, 126.7, 113.5, 113.0, 44.7, 40.3, 30.4, 19.3, 13.4.
Anal. Calcdfor C19H19N3S2: C, 64.56;H, 5.42; N, 11.89. Found:C, 64.34;
H, 5.47; N, 11.85.
1-(4-Bromo-2-thienyl)-N-(3-butylbenzimidazol-3-ium-1-yl)-
methanimine iodide (6c): Brown crystals (100%), mp 175.0ꢀ176.0 °C;
1H NMR (DMSO-d6) δ 10.54 (s, 1H), 9.59 (s, 1H), 8.25ꢀ8.21 (m, 2H),
8.11ꢀ8.07 (m, 1H), 7.98 (s, 1H), 7.80ꢀ7.75 (m, 2H), 4.59 (t, J = 7.2 Hz,
2H), 2.01 (quintet, J = 7.2 Hz, 2H), 1.44 (sextet, J = 7.5 Hz, 2H), 0.97 (t, J =
7.4 Hz, 3H); 13C NMR (DMSO-d6) δ 155.5, 137.7, 136.5, 136.4, 131.4,
130.0, 129.0, 127.4, 127.0, 113.9, 113.0, 110.4, 47.1, 30.3, 19.0, 13.4. Anal.
Calcd for C16H17IBrN3S: C, 39.20; H, 3.50; N, 8.57. Found: C, 39.08; H,
3.60; N, 8.17.
1-[(E)-(4-Bromo-2-thienyl)methyleneamino]-3-butylben-
zimidazol-3-ium-2-carbodithioate (9c): Red crystals (68%), mp
1
170.0ꢀ173.0 °C; H NMR (DMSO-d6) δ 9.47 (s, 1H), 8.16 (s, 1H),
8.10ꢀ8.03 (m, 1H), 7.98ꢀ7.93 (m, 1H), 7.90 (s, 1H), 7.75ꢀ7.65 (m, 2H),
4.46ꢀ4.38 (m, 2H), 1.95ꢀ1.85 (m 2H), 1.45ꢀ1.32 (m, 2H), 0.89 (t, J= 7.2
Hz, 3H); 13C NMR (DMSO-d6) δ 221.9, 160.7, 146.6, 138.4, 136.3, 131.4,
128.2, 127.0, 126.8, 113.6, 112.9, 110.2, 44.8, 30.3, 19.3, 13.4. Anal. Calcd for
C17H16BrN3S3: C, 46.57; H, 3.68; N, 9.58. Found: C, 46.26; H, 3.53; N, 9.30.
1,3-Dimethylbenzimidazol-3-ium-2-carbodithioate (10):
Red crystals (85%), mp 235.0ꢀ236.0 °C (lit.37 mp 237ꢀ238 °C); 1H
NMR (DMSO-d6) δ 7.92 (dd, J = 6.0, 3.0 Hz, 2H), 7.64 (dd, J = 6.0, 3.0
Hz, 2H), 3.88 (s, 6H); 13C NMR (DMSO-d6) δ 223.8, 151.5, 129.9,
126.0, 112.9, 31.0. Anal. Calcd for C10H10N2S2: C, 54.02; H, 4.53; N,
12.60. Found: C, 53.87; H, 4.44; N, 12.39.
N-(3-Butylbenzimidazol-3-ium-1-yl)-1-(p-tolyl)methanimine
1
iodide (6d): White crystals (100%), mp 167.0ꢀ169.0 °C; H NMR
(DMSO-d6) δ 10.55 (s, 1H), 9.38 (s, 1H), 8.23ꢀ8.19 (m, 1H), 8.17ꢀ8.12
(m, 1H), 7.97 (t, J = 8.1 Hz, 2H), 7.79ꢀ7.74 (m, 2H), 7.47 (d, J = 7.8 Hz,
2H), 4.59 (t, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.08ꢀ1.98 (m, 2H), 1.50ꢀ1.40
(m, 2H), 0.98 (t, J = 7.4 Hz, 3H); 13C NMR (DMSO-d6) δ 162.5, 143.9,
135.9, 130.0, 129.4, 129.2, 128.5, 127.3, 127.0, 113.9, 113.1, 47.1, 30.4, 21.4,
19.1, 13.4. Anal. Calcd for C19H22IN3: C, 54.42; H, 5.29; N, 10.02. Found: C,
54.43; H, 5.31; N, 9.90.
(1,3-Dimethylbenzimidazol-3-ium-2-carbothioyl)isopro-
pylazanide (12): Colorless crystals (86%), mp 140.0ꢀ141.0 °C; 1HNMR
(DMSO-d6) δ 8.14 (dd, J = 6.3, 3.0 Hz, 2H), 7.74 (dd, J = 6.3, 3.0 Hz, 2H),
3.99 (s, 6H), 1.37 (d, J= 6.6 Hz, 6H); 13C NMR (DMSO-d6) δ173.9, 145.1,
N-(3-Butylbenzimidazol-3-ium-1-yl)-1-(4-nitrophenyl)me-
thanimine iodide (6e): Brown crystals (100%), mp 217.0ꢀ219.0 °C;
1H NMR (DMSO-d6) δ 10.57 (s, 1H), 9.55 (s, 1H), 8.47 (d, J = 8.4 Hz,
2H), 8.32 (d, J = 8.7 Hz, 2H), 8.28ꢀ8.20 (m, 2H), 7.83ꢀ7.77 (m, 2H),
4.60(t, J = 7.2 Hz, 2H), 2.01 (quintet, J = 7.4 Hz, 2H), 1.44 (sextet, J = 7.8
Hz, 2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (DMSO-d6) δ 160.0, 149.8,
137.0, 136.5, 130.3, 130.1, 129.4, 127.6, 127.3, 124.4, 114.0, 113.3, 47.2,
30.4, 19.1, 13.4. Anal. Calcd for C18H19IN4O2: C, 48.01; H, 4.25; N,
12.44. Found: C, 47.73; H, 4.14; N, 12.18.
4-[(E)-(3-Butylbenzimidazol-3-ium-1-yl)iminomethyl]-N,N-
diethylaniline iodide (6f): Yellow microcrystals (100%), mp 151.0ꢀ
152.0 °C; 1H NMR (DMSO-d6) δ 10.35 (s, 1H), 9.03 (s, 1H), 8.18ꢀ8.14
(m, 1H), 8.07ꢀ8.03 (m, 1H), 7.80 (d, J = 9.0 Hz, 2H), 7.74ꢀ7.71 (m, 2H),
6.85 (d, J = 9.0 Hz, 2H), 4.53 (t, J = 7.2 Hz, 2H), 3.47 (q, J = 6.8 Hz, 4H),
1.97 (quintet J = 7.5 Hz, 2H), 1.41 (sextet, J = 7.5 Hz, 2H), 1.15 (t, J = 7.0
Hz, 6H), 0.95 (t, J = 7.2 Hz, 3H); 13C NMR (DMSO-d6) δ 163.0, 151.3,
135.5, 131.6, 130.1, 129.5, 126.9, 126.9, 116.9, 113.7, 113.1, 111.3, 46.8, 44.0,
30.6, 19.1, 13.4, 12.4. Anal. Calcd for C22H29IN4: C, 55.47; H, 6.14; N, 11.76.
Found: C, 55.11; H, 6.13; N, 11.57.
130.5, 127.3, 113.7, 47.8, 32.2, 20.2. Anal. Calcd for C13H17N3S H2O: C,
3
58.84; H, 7.22; N, 15.83. Found: C, 58.97; H, 7.40; N, 15.86.
General Method for the Preparation of Spirocyclic Deri-
vatives (13a,b): Sodium hydride (1.2 equiv) was added to a mixture
of isopropyl isothiocyanate (2.2 equiv) and the corresponding N-(3-
butylbenzimidazol-3-ium-1-yl)-1-(aryl)methanimine iodides 6a, in dry
THF and stirred for 5 h at room temperature under argon. The
solution was filtered, the filtrate concentrated under reduced pressure,
and the residue was recrystallized from EtOAc to obtain pure spir-
ocyclic derivatives 13a,b as red crystals.
1-Butyl-10,30-diisopropyl-3-[(E)-(4-methoxyphenyl)methyl-
eneamino]spiro[benzimidazole-2,50-imidazolidine]-20,40-dithi-
one (13a): Red crystals (77%), mp 141.0ꢀ142.0 °C; 1H NMR (DMSO-
d6) δ7.84 (s, 1H), 7.51 (d, J= 8.7 Hz, 2H), 7.26 (d, J =7.2 Hz, 1H), 6.97(d,
J = 8.7 Hz, 2H), 6.83 (t, J = 7.5 Hz, 1H), 6.72 (t, J = 7.3 Hz, 1H), 6.65 (d, J =
7.5 Hz, 1H), 5.68 (br s, 1H), 4.13ꢀ4.03 (m, 1H), 3.77 (s, 3H), 3.19ꢀ2.96
(m, 2H), 1.65ꢀ1.52 (m, 8H), 1.38ꢀ1.29 (m, 5H), 1.23 (d, J = 6.9 Hz, 3H),
0.86 (t, J=7.2Hz, 3H);13C NMR (DMSO-d6) δ160.3, 139.6, 136.6, 132.2,
127.4, 121.4, 118.2, 114.3, 107.8, 104.8, 103.9, 99.4, 55.2, 42.8, 29.6, 19.8,
19.0, 17.9, 13.5. Anal. Calcd for C27H35N5OS2: C, 63.62; H, 6.92; N, 13.74.
Found: C, 63.80; H, 7.21; N, 13.76.
1,3-Dimethylbenzimidazol-3-ium iodide (7): White needles
(94%), mp 193.0 °C (lit.48 mp 190ꢀ191 °C); 1H NMR (DMSO-d6) δ
9.76 (s, 1H), 8.12ꢀ7.98 (m, 2H), 7.76ꢀ7.65 (m, 2H), 4.12 (s, 6H); 13C
NMR (DMSO-d6) δ 142.8, 131.4, 126.2, 113.2, 33.5.
1-[(E)-Benzylideneamino]-3-butyl-10,30-diisopropylspiro-
[benzimidazole-2,50-imidazolidine]-20,40-dithione (13b): Red
General Method for the Preparation of NHC CS2 Betaines
3
9aꢀc, 10: Sodium hydride (1.2 equiv) was added to a mixture of carbon
disulfide (2 equiv) and 1,3-dimethylbenzimidazolium iodide 7 or N-(3-
butylbenzimidazol-3-ium-1-yl)-1-(aryl)methanimine iodides 6aꢀc in dry
THF and stirred for 5 h (12 h in the case of 7) at room temperature under
argon. The solution was filtered, the filtrate concentrated under reduced
1
crystals (74%), mp 116.0ꢀ119.0 °C; H NMR (DMSO-d6) δ 7.85 (s,
1H), 7.61ꢀ7.55(m, 2H), 7.42ꢀ7.30 (m, 4H), 6.86 (t, J= 7.7 Hz, 1H), 6.74
(t, J = 7.7 Hz, 1H), 6.67 (d, J = 7.6 Hz, 1H), 5.68 (br s, 1H), 4.16ꢀ4.05 (m,
1H), 3.20ꢀ2.97 (m, 2H), 1.64ꢀ1.48 (m, 8H), 1.38ꢀ1.29 (m, 5H), 1.23
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NOTE
(d, J = 7.0 Hz, 3H), 0.86 (t, J = 7.3 Hz, 3H); 13C NMR (DMSO-d6) δ
139.0, 136.6, 134.8, 131.9, 129.2, 128.7, 125.8, 121.8, 118.2, 108.3, 105.0,
103.6, 42.8, 29.5, 19.8, 19.0, 17.9, 13.6. Anal. Calcd for C26H33N5S2: C,
65.10; H, 6.93; N, 14.60. Found: C, 65.10; H, 7.06; N, 14.58.
3-[(E)-(4-Methoxyphenyl)methyleneamino]benzimidazol-
1-ium-1-amine; 2,4-Dinitrophenolate (19a): Yellow microcrys-
tals (42%), mp 146.0ꢀ148.0 °C; 1H NMR (DMSO-d6) δ 10.40 (s, 1H),
9.23(s, 1H), 8.58 (d, J = 3.9 Hz, 1H), 8.13ꢀ8.09 (m, 1H), 8.01ꢀ7.95 (m,
3H), 7.80ꢀ7.72 (m, 3H), 7.19 (d, J = 8.8 Hz, 2H), 7.13 (s, 2H), 6.30 (d,
J = 9.8 Hz, 1H); 13C NMR (DMSO-d6) δ 170.3, 165.1, 163.4, 162.5,
136.0, 131.3, 131.1, 128.5, 127.4, 126.9, 126.5, 125.0, 123.7, 114.9, 113.3,
112.9, 109.2, 55.7. Anal. Calcd for C21H18N6O6: C, 56.00; H, 4.03; N,
18.66. Found: C, 55.86; H, 3.86; N, 18.58.
3-[(E)-p-Tolylmethyleneamino]benzimidazol-1-ium-1-amine;
2,4-Dinitrophenolate (19d): Brown microcrystals (40%), mp 132.0ꢀ
134.0 °C; 1H NMR (DMSO-d6) δ 10.45 (s, 1H), 9.28 (s, 1H), 8.58 (d, J =
3.3 Hz, 1H), 8.14ꢀ8.11 (m, 1H), 8.01ꢀ7.97 (m, 1H), 7.92 (d, J = 7.9 Hz,
2H), 7.80ꢀ7.72 (m, 3H), 7.45 (d, J = 7.9 Hz, 2H), 7.16 (s, 2H), 6.32 (d, J =
9.8 Hz, 1H), 2.43 (s, 3H); 13C NMR (DMSO-d6) δ 169.9, 162.5, 143.9,
136.0, 135.9, 131.0, 129.9, 129.1, 128.6, 128.5, 127.7, 127.5, 127.4, 126.9,
126.3, 124.8, 113.2, 112.9, 21.3. Anal. Calcd for C21H18N6O5: C, 58.06; H,
4.18; N, 19.35. Found: C, 57.64; H, 4.05; N, 19.38.
3-[(E)-[4-(Diethylamino)phenyl]methyleneamino]benzimi-
dazol-1-ium-1-amine; 2,4-Dinitrophenolate (19f): Brown micro-
crystals (60%), mp 180.0 °C; 1H NMR (DMSO-d6) δ10.38 (s, 1H), 9.01 (s,
1H), 8.63 (d, J = 2.7 Hz, 1H), 8.04 (d, J = 7.5 Hz, 1H), 7.98 (d, J = 7.8 Hz,
1H), 7.88 (dd, J= 9.6, 3.0 Hz, 1H), 7.80ꢀ7.68 (m, 4H), 7.09 (br s, 2H), 6.83
(d, J = 8.7 Hz, 2H), 6.50 (d, J = 9.6 Hz, 1H), 3.46 (q, J = 6.6 Hz, 4H), 1.16 (t,
J = 6.8 Hz, 6H); 13C NMR (DMSO-d6) δ 168.6, 162.8, 151.2, 136.0, 135.7,
131.5, 131.1, 129.0, 128.5, 127.7, 127.0, 126.7, 125.5, 124.5, 117.0, 113.1,
112.8, 111.1, 43.9, 12.3. Anal. Calcd for C24H25N7O5: C, 58.65; H, 5.13; N,
19.95. Found: C, 58.32; H, 5.26; N, 19.88.
General Method for the Preparation of NHC RC(O)NCS
3
Betaines 15aꢀc, 16. Sodium hydride (1.2 equiv) was added to a mixture
of benzoylisothiocyanate and the corresponding N-(3-butylbenzimidazol-3-
ium-1-yl)-1-(aryl)methanimine iodides 6aꢀc in 1/1 molar ratio in dry THF
and stirred for 5 h (12 h in the case of 7) at room temperature under argon.
The solution was filtered, the filtrate concentrated under reduced pressure,
and the residue was purified by flash chromatography using EtOAc/hexanes
to obtain betaine adducts 15aꢀc, 16.
Benzoyl-[1-butyl-3-[(E)-(4-methoxyphenyl)methylene-
amino]benzimidazol-1-ium-2-carbothioyl]azanide (15a): Yel-
low microcrystals (83%), mp 126.0ꢀ128.0 °C; 1H NMR (DMSO-d6) δ
9.35 (s, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.03ꢀ7.94 (m, 5H), 7.75ꢀ7.65 (m,
2H), 7.53 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.7 Hz, 2H), 7.18 (d, J = 8.7 Hz,
2H), 4.63 (t, J = 7.2 Hz, 2H), 3.89 (s, 3H), 2.02ꢀ1.92 (m, 2H), 1.47ꢀ1.36
(m, 2H), 0.91 (t, J = 7.2 Hz, 3H); 13C NMR (DMSO-d6) δ 179.1, 169.8,
168.2, 163.6, 145.1, 133.7, 132.3, 131.6, 129.2, 128.9, 128.3, 127.5, 126.8,
123.8, 114.8, 113.6, 113.2, 55.7, 45.2, 30.6, 19.4, 13.5. Anal. Calcd for
C27H26N4O2S: C, 68.91; H, 5.57; N, 11.91. Found: C, 68.63; H, 5.63;
N, 11.73.
Benzoyl-[1-[(E)-benzylideneamino]-3-butylbenzimidazol-
3-ium-2-carbothioyl]azanide (15b): Yellow crystals (77%), mp
125.0ꢀ127.0 °C; 1H NMR (DMSO-d6) δ 9.48 (s, 1H), 8.18ꢀ8.08 (m,
2H), 8.04ꢀ7.94 (m, 4H), 7.78ꢀ7.69 (m, 3H), 7.63 (t, J = 7.4 Hz, 2H),
7.53 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.5 Hz, 2H), 4.64 (t, J = 7.3 Hz, 2H),
2.05ꢀ1.93 (m, 2H), 1.43 (sextet, J = 7.4 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H);
13C NMR (DMSO-d6) δ 179.0, 169.8, 168.1, 145.3, 133.7, 133.5, 132.3,
131.3, 129.3, 129.1, 128.9, 128.2, 127.2, 126.9, 126.9, 113.6, 113.2, 45.2,
30.5, 19.3, 13.4. Anal. Calcd for C26H24N4OS: C, 70.88; H, 5.49; N, 12.72.
Found: C, 70.57; H, 5.60; N, 12.51.
Benzoyl-[1-[(E)-(4-bromo-2-thienyl)methyleneamino]-3-
butylbenzimidazol-3-ium-2-carbothioyl]azanide (15c): Yel-
low crystals (74%), mp 151.0ꢀ154.0 °C; 1H NMR (DMSO-d6) δ 9.55 (s,
1H), 8.18 (s, 1H), 8.11 (d, J = 8.1 Hz, 1H), 8.05 (d, J = 7.3 Hz, 1H), 7.98 (d,
J = 7.2 Hz, 2H), 7.87 (s, 1H), 7.75ꢀ7.66 (m, 2H), 7.55 (t, J = 7.2 Hz, 1H),
7.41 (t, J = 7.4 Hz, 2H), 4.61 (t, J = 7.2 Hz, 2H), 1.99ꢀ1.90 (m, 2H),
1.46ꢀ1.34 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); 13C NMR (DMSO-d6) δ
179.1, 170.1, 161.0, 145.6, 138.7, 136.5, 133.8, 132.5, 131.8, 129.4, 129.0,
128.6, 128.4, 127.1, 127.1, 113.8, 113.3, 110.4, 45.4, 30.5, 19.4, 13.5. Anal.
Calcd for C24H21BrN4OS2: C, 54.86; H, 4.03; N, 10.66. Found: C, 55.19; H,
4.09; N, 10.42.
’ ASSOCIATED CONTENT
Supporting Information. 1H and 13C spectra for 4aꢀf,
S
b
6aꢀf, 7, 9aꢀc, 10, 12, 13a,b, 15aꢀc, 16, 18, 19a, 19d, and 19f
and the X-ray crystal structure and data of 9a, 13a, and 16 as CIF
files. This material is available free of charge via the Internet at
http://pubs.acs.org.
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midazole 2 or its imine derivatives 4aꢀf in dichloromethane/ethanol
(5:1) was added 1.2ꢀ1.5 equiv of O-(2,4-dinitrophenyl)hydroxylamine
with stirring over a period of 2ꢀ3 min. The mixture was heated under
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Brown microcrystals (80%), mp 166.0ꢀ168.0 °C; 1H NMR (DMSO-d6) δ
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4086
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