A convenient synthesis of imidazolium salts and trisubstituted ethylenediamine derivatives

Article abstract of DOI:10.1081/SCC-120003643

A series of 1,2-dimethyl-3-arylsulfonyll-4,5-dihydroimidazolium iodides (7-11) was prepared by convenient sulfonylation and methylation from commercially available 2-methyl-2-imidazoline. Trisubstituted ethylenediamine derivatives 12-21 were synthesized f

Full text of DOI:10.1081/SCC-120003643

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A CONVENIENT SYNTHESIS OF IMIDAZOLIUM SALTS AND
TRISUBSTITUTED ETHYLENEDIAMINE DERIVATIVES
Chizhong Xia a , Hongxing Wang a , Bingjun Zhao a , Jianxin Chen a , Congmin Kang a ,
Yanping Ni a & Peiwen Zhou a
a Institute of Molecular Science , Shanxi University , Taiyuan, 030006, China
Published online: 17 Aug 2006.
To cite this article: Chizhong Xia , Hongxing Wang , Bingjun Zhao , Jianxin Chen , Congmin Kang , Yanping Ni & Peiwen Zhou
(2002) A CONVENIENT SYNTHESIS OF IMIDAZOLIUM SALTS AND TRISUBSTITUTED ETHYLENEDIAMINE DERIVATIVES, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:9, 1447-1455, DOI:
10.1081/SCC-120003643
To link to this article: http://dx.doi.org/10.1081/SCC-120003643
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SYNTHETIC COMMUNICATIONS, 32(9), 1447–1455 (2002)
A CONVENIENT SYNTHESIS OF
IMIDAZOLIUM SALTS AND
TRISUBSTITUTED ETHYLENEDIAMINE
DERIVATIVES
Chizhong Xia, Hongxing Wang, Bingjun Zhao,
Jianxin Chen, Congmin Kang, Yanping Ni, and
*
Peiwen Zhou
Institute of Molecular Science, Shanxi University,
Taiyuan, 030006, China
ABSTRACT
A series of 1,2-dimethyl-3-arylsulfonyl1-4,5-dihydroimidazol-
ium iodides (7–11) was preparedby convenient sulfonylation
andmethylation from commercially available 2-methyl-2-
imidazoline. Trisubstituted ethylenediamine derivatives
12–21 were synthesized from the reduction or hydrolysis of
imidazolium salts 7–11 in high yield.
2-Oxazoline chemistry has been intensively investigatedandfound
great utility in organic synthesis, as examplifedby the Meyers synthetic
1
methodfor optically active carboxylic acids, the wide use of the oxazoline
protective group for acids,2 andthe use of the oxazoline directing group
*Corresponding author. Current address: Prolinx, Inc. 22322 20th Ave. SE, Bothell,
WA 98021, USA.
1447
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1448
XIA ET AL.
3
in ortho andlateral lithations of aromatic compounds.
In contrast, the
chemistry of 2-imidazoline and imidazolium salts has not been fully inves-
tigateddespite the obvious structure similarity between 2-oxazoline and2-
imidazoline. 2,3-Diarylimidazolium iodides have been prepared and their
nucleophilic reactions were explored.4,5,6 In our earlier work these imidazo-
lium iodides were used as the tetrahydrofolate coenzyme model compounds
for one-carbon unit transfer reaction. Pandit reported the synthesis of 3-
acetyl (tolylsulfonyl)-1,4,4-trimethyl-4,5-dihydroimidazolium iodides and
demonstrated their utilities as an entry to mimic the function of tetrahydro-
folate coenzymes in one-carbon unit transfer reactions.7–9
Having notedthe structural analogy of 2-methyl-2-imidazoline and
2-methyl-2-oxazoline, we considered the exploration of the synthetic utilities
of 2-methyl-2-imidazoline a worthy endeavor. Compared with 2-oxazoline,
2-imidazoline is easily alkylated to produce imidazolium salts, the C-N bond
in the imidazolium is more reluctant to break, its C(2) electrophilic reactivity
can be increasedby the formation of an imidazolium salt (Figure 1), its
C(2)-methyl group can also be deprotonated and the lithiated species can
10
be quenchedby nucleophiles.
These differences effect significantly
the behavior of the imidazolium system. On the other hand, 2-methyl-2-
imidazoline is a representative example for imidazoline chemistry and also
commercially available. Based on this understanding 1,2-dimethyl-3-arylsul-
fonyl-4,5-dihydroimidazolium iodides (7–11) have been designed, and the
C(2) electrophility was adjusted by different substituents on N(1) and N(3).
The preparation of the imidazoliums 7–11 was straightforwardin two
steps with high yields from commercially available 2-methyl-2-imidazoline
(1): 2-methyl-arylsulfonylimidazoline (2–6) were preparedby sulfonylation
of 2-methyl-2-imidazoline with arylsulfonyl chlorides under basic con-
ditions, and further methylation by iodomethane gave imidazolium salts
(7–11) (Scheme 1). Both modifications should increase the C(2) suscepti-
bility to nucleophiles. The imidazolium salts 7–11 have higher melting
points comparedwith their precursors 2–6, which can be accountedby
their salt nature. Significant difference of n C¼N bondin their infrared
spectra was only foundbetween theÀ1 p-(m-) nitro substituted 5, 6 and
10, 11. It increasedby about 14 cm
after methylation. This difference
Figure 1.

IMIDAZOLIUM SALTS
1449
X
Product
Yield (%)
Product
Yield (%)
H
2
3
4
5
6
91
93
93
80
85
7
8
9
92
94
95
90
90
p-Me
p-OMe
p-NO2
m-NO2
10
11
Scheme 1.
may be explainedby the resonance cation structure of imidazolium salts
(Figure 1), since electron withdrawing nitro group could affect this system
more than the relatively isolatedsystem in the imidazoline 5 and 6. The
difference was also observed in 13C NMR, andthe chemical shifts values
for C(2) in the imidazolium 7–9 were quite similar, between 165.5 and
166.6 ppm. This value for imidazolium system in 10 and 11, however, was
observed downfield at 170.5 and 171.0 ppm respectively. This indicated that
both 10 and 11 may be expectedto have different reactivity than 7–9. The
substituents on the arylsulfonyl of the imidazolium salts 7–11 did not have
much effect on the C(2) electronic properties, when X was hydrogen, methyl,
or methoxy. Only the strong electron withdrawing nitro group has a mean-
ingful effect on the imidazolium C(2) electronic properties.
Reduction of the imidazolium salts 7–11 by sodium borohydride pro-
duced N-[2-(N0-ethyl-N0-methyl)ethyl]arylsulfonylamides (12–16) as shown
in Scheme 2. No tetrahydroimidazole intermediate has been detected; only
ring-opened benzenesulfonamide derivatives were obtained. Pandit reported
the reduction of 1,4,4-trimethyl-4,5-dihydroimidazolium to produce exclu-
sively partially reduced cyclic tetrahydroimidazole products.11 Reduction of
2,3-diaryl-4,5-dihydroimidazolium salts gave both tetrahydroimidazoles and
ring-opened products, or in some cases only tetrahydroimidazole intermedi-
ates.12 It was reasonable to assume that formation of a tetrahydroimidazole
or a ring-opened derivative from the imidazolium reduction mainly
depend on the balance between steric and electric interactions of the
substituents.
Hydrolysis of the imidazolium 7–11 produced N-[2-(N0-acetyl-N0-
methyl)ethyl]arylsulfonamides (17–21) as shown in Scheme 2. Both 10 and
11 are sensitive to moisture and rapidly decomposed when exposed to air.

1450
XIA ET AL.
X
Product
Yield (%)
Compound
Product
Yield (%)
H
12
13
14
15
16
94
97
85
85
96
7
8
9
17
18
19
20
21
94
96
96
98
98
4-Me
4-OMe
4-NO2
3-NO2
10
11
Scheme 2.
Hydrolysis of 10 and 11 was also conducted in water. This sensitivity can be
explainedby the m- or p- nitro electron-wthdrawing group, which dramati-
cally increasedthe susceptibility of the imidazolium C(2) to nucleophilic
attack, as indicated by the 13C NMR andIR frequency for the C ¼N
double bond.
In summary, from commercially available 2-methyl-2-imidazoline,
arylsulfonylimidazolium 7–11 were preparedby a convenient two-step
sulfonylation and methylation procedure. Reduction and hydrolysis
producedring-openedcompounds
12–21. In three steps some N,N,N0-tri-
substitutedethylenediamine derivatives were preparedin high yieldfrom
commercially available 2-methyl-2-imidazoline.
EXPERIMENTAL
MS spectra were obtainedon a JMS-D300 GC/MS spectrometer. The
1H and 13C NMR were obtainedon a JOEL FX-60Q, Varian FT-80A or
Bruker AC-P 300 MHz, with TMS as an internal standard. Combustion
analyses were performedon a Perkin-Elmer 240C or a MOD 1106 instru-
ment. IR spectra were obtainedon a Shimadzu IR-1700 spectrophotometer.
Melting points were uncorrected. All reactions were performed according to
the scale of the general procedures, and under an inert atmosphere of nitro-
gen. All reagents andsolvents were purifiedanddriedas required.
General procedure for the preparation of 2-methyl-1-arylsulfonylimida-
zolines (2–6), 2-methyl-1-benzenesulfonylimidazoline (2) as an example:
2-Methyl-2-imidazoline 1 (4.0 g, 48.0 mmol) was dissolved in 20 ml dry

IMIDAZOLIUM SALTS
1451

1452
XIA ET AL.

IMIDAZOLIUM SALTS
1453

1454
XIA ET AL.
methylene chloride at 0ꢀC, followed by the addition of triethyl amine
(7.0 ml, 50.2 mmol). To this solution was added dropwise a solution
of benzenesulfonyl chloride (8.5 g, 48.0 mmol) in 10 ml methylene chloride.
The mixture was stirredandwarmedto RT in an aidtdional 2 h.
The reaction mixture was washedwith saturatedsoidum bicarbonate
(20 ml) andwater (20 ml), andrdiedover anhyrdous soidum sulfate.
Evaporation of methylene chloride in vacuo gave a crude solid, which was
recrystallizedfrom anhydrous ethyl alcohol to yield9.8 g (91%) of
white crystals.
2 as
General procedure for the preparation of 1,2-dimethyl-3-arylsulfonyl-
4,5-dihydroimidazolium iodides (7–11), 1,2-dimethyl-3-benzenesulfonyl-4,5-
dihydroimidazolium iodide 7 as an example: Imidazoline 2 (3.76 g,
16.8 mmol) andiodiomethane (3.14 ml, 50.4 mmol) were refluxedin 20 ml
dry methylene chloride for 6 h. After cooling to room temperature a pre-
cipitate was collectedby filtration andcrystallizedfrom anhydrous ethyl
alcohol to give 5.6 g (92%) of 7 as a white powder.
General procedure for the reduction of 1,2-dimethyl-3-arylsulfonyl-4,5-
dihydroimidazolium iodides (7–11), N-[2-(N0-ethyl-N0-methyl)ethyl]-4-meth-
oxylbenzenesulfonamide 14 as an example: To a solution of imidazolium
9 (1.6 g, 4.0 mmol) in 20 ml dry ethyl alcohol was added 0.30 g sodium
borohydride. The mixture was stirred for 1.5 h at RT. 30 ml saturated
ammonium chloride solution was added dropwise and continuously stirred
until bubbling subsided, then extracted with chloroform (3 ꢁ 25 ml). The
combinedorganic layers were washedwith water, driedover anhydrous
sodium sulfate, and concentrated to offer 0.93 g (85%) of 14 as a white
solid.
General procedure for the hydrolysis of 1,2-dimethyl-3-arylsulfonyl-4,5-
dihydroimidazolium iodides (7–11) with sodium hydroxide solution, N-[2-(N0-
acetyl-N0-methyl)ethyl]-4-methoxylbenzenesulfonamide 19 as an example: To
a solution of the imidazolium 9 (0.8 g, 2.0 mmol) in 10 ml ethyl alcohol was
added to 10 ml 5% sodium hydroxide solution. The mixture was stirred for
1.5 h at RT. The resultedsolution was extractedwith ethyl acetate
(3 ꢁ 30 ml); the combinedorganic layers were washedwith water and
dried over anhydrous sodium sulfate. Evaporation of the solvent in vacuo
gave a residue, which was recrystallized from benzene to get 0.47 g (98%) of
19 as a white solid.
General procedure for the hydrolysis of 1,2-dimethyl-3-arylsulfonyl-4,5-
dihydroimidazolium iodides 10 and 11 in water, N-[2-(N0-acetyl)-N0-methyl)-
ethyl]-4-nitrobenzenesulfonamide 20 as an example: A solution of the
imidazolium 10 (411.0 mg, 1.0 mmol) in 10 ml water was stirredfor 2 h at
RT anda precipitate was observed. The suspension was collectedby vacuum
filtration anddriedto offer 295 mg (98%) of 20 as white crystals.

IMIDAZOLIUM SALTS
1455
ACKNOWLEDGMENTS
This work was supportedby the National Nature Science Foundation
of China, andthe Natural Science Foundation of Shanxi Province, China.
The authors wouldlike to thank Professor Nick R. Natale, at the University
of Idaho, for his helpful suggestions.
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Receivedin the USA May 10, 2001