A convenient synthesis of 1-tosyl-3, 4-dimethyl imidazolium salt and N,N,N′-trisubstituted ethylendiamine derivatives

Article abstract of DOI:10.1081/SCC-200030990

1-Tosyl-3,4-dimethyl imidazolium iodide 3 was prepared by convenient cyclization, sulfonylation, and methylation from 4-methyl-2-imidazoline, which was obtained by the reaction of ethyl formate with 1,2-diaminopropane. Monofunctional carbon nucleophiles r

Full text of DOI:10.1081/SCC-200030990

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 19, pp. 3535–3543, 2004
A Convenient Synthesis of 1-Tosyl-3,
4-Dimethyl Imidazolium Salt and N,N,N0-
Trisubstituted Ethylendiamine Derivatives
Donghong Li, Junsheng Hao, Bing Deng, Wei Guo,
*
Fangjun Huo, Yongbin Zhang, and Chizhong Xia
School of Chemistry and Chemical Engineering,
Shanxi University Taiyuan, 030006, China
ABSTRACT
1-Tosyl-3,4-dimethyl imidazolium iodide 3 was prepared by convenient
cyclization, sulfonylation, and methylation from 4-methyl-2-imidazoline,
which was obtained by the reaction of ethyl formate with 1,2-diaminopro-
pane. Monofunctional carbon nucleophiles reacted with 3 to yield a series
of N,N,N0-trisubstituted ethylendiamine derivatives.
Key Words: Synthesis; THF coenzyme model; N,N,N0-trisubstituted
ethylendiamine; 1-tosyl-3,4-diamethyl-imidazolium.
*
Correspondence: Chizhong Xia, School of Chemistry and Chemical Engineering,
Shanxi University Taiyuan, 030006, China; E-mail: guow@sxu.edu.cn.
3535
DOI: 10.1081/SCC-200030990
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Li et al.
Tetrahydrofolate (THF) was responsible for transfer of one-carbon
fragment in biological synthesis and metabolism.[1] Thus, the study on the
THF coenzyme model may provide a valuable class of reagents for group
transfer reactions for practical utility.[2,3] In order to investigate different
types of models that would be capable of transferring substituted one-
carbon unit, a series of 1-aryl-2,3-dimethyl-4,5-dihydroimidazolium iodides
in our earlier research had been synthesized to improve their potential in
one-carbon unit transfer reactions as the THF coenzyme model. One important
approach was to adjust the basicity of N(1), C(2), and N(3) in the imidazolium
by using different substituted groups.[4] However, the improvement was
unobvious by adjusting different substituted groups of N(1) and N(3) in the
imidazolium.[5] Consequently, we presumed that the reactions were affected
by the steric hindrance and induced effect on C(2). A key approach was to
adjust different substituted of N(1), C(2), and C(4) in the imidazolium. In
addition, Pandit’s group had reported two model compounds: 1-tosyl-3,4,4-tri-
methyl-imidazolinium iodide and 1-tosyl-3,4,4,5,5-pentamethyl-imidazoli-
nium iodide. From their experiment results, it could be seen that 1-tosyl-
3,4,4-trimethyl-imidazolinium iodide was more electrophilic than 1-tosyl-
3,4,4,5,5-pentamethyl-imidazolinium iodide.[6] We extrapolated that if some
methyls in imidazoline were reduced, the electrophilic ability would be
improved. Although the most simple imidazoline (without methyl groups con-
nected to carbons) was described in the literature,[7] it was difficult to prepare
and not easy to handle due to its reactivity with carbon dioxide under
atmospheric conditions. Hence, we chose 4-methyl imidazoline as a matrix
and our new model, 1-tosyl-3, 4-dimethyl-imidazolinium iodide 3, was
synthesized.
Imidazolium iodide 3 was synthesized from 1,2-diaminopropane in three
steps: (1) cyclization of 1,2-diaminopropane by ethyl formate in basic
conditions produced 4-methyl imidazoline 1; (2) sulfonylation of 1 by tosyl
chloride under basic conditions obtained 1-tosyl-4-methyl imidazoline 2; (3)
further methylation of 2 by reflux with excess iodomethane in benzene syn-
thesized imidazolium salt 3 in the yield of 81%. The synthesis process was
shown in Sch. 1.
Furthermore, the structure of 1-tosyl-3, 4-dimethyl imidazolium iodide 3
had been determined by X-ray diffraction, the structure of which was shown in
Fig. 1.
It was observed from the X-ray that the length of N2—C11 and N1—C11
were 1.272(8)/%A and 1.325(7)/%A; they were much shorter than standard
single C—N bond [Lide (1962) pointed out that the standard single and
doubled C—N bond lengths are 1.474 and 1.265/%A]. It suggested that the
positive charge delocalized among N1—C11—N2, thus C11 had become
the reaction point of nucleophilic reagents in the imidazoline ring.

A Convenient Synthesis of 1-Tosyl-3,4-Dimethyl Imidazolium Salt
3537
Scheme 1.
In our current research, through a series of attempts towards different
nucleophilic reagents,[8] model compound 3 was found to be more electro-
philic. When 1-tosyl-3,4-dimethyl imidazolium iodide 3 was treated with a
malononitrile, ethyl malonate, and nitromethane, the corresponding N,N,N0-
trisubstituted 2-methyl-ethylenediamines 4, 5, and 6 were produced in the
yield of 79–95%. These experiments were carried out by stirring in tetra-
hydrofuran and the reaction time depended on the nucleophilicity of carbon
anion, generally from 1 to 5 h. When the mixture was cooled to 08C, the
products 4 and 5 were crystallized as white crystals and the product 6 was
purified by column chromatography as an oil. Compared with our earlier
results,[9,10] the model compound 3 proved to be more electrophilic under
the same conditions. Some data was shown in Table 1.
Figure 1. X-ray structure of 1-tosyl-3,4-dimethyl imidazolium iodide 3.

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Li et al.
Table 1. Comparison of model compound 3 with the other models reported before.
Reaction
time (h)
Yield
(%)
Model compound
Reagent
CH2(CN)2
CH3NO2
overnight
2
85
59
CH2(CN)2
CH2(CN)2
CH2(CN)2
4.5
—
—
82
77
78
CH2(CN)2
CH3NO2
—
overnight
60
92
CH2(CN)2
CH3NO2
2
1
89
95
aAll reactions were performed in tetrahydrofuran.
We considered that a possible mechanism is that nucleophilic addi-
tion to the C55N double bond in the imidazolium forms an imidazolidine
intermediate, which subsequently leads to ring-opened products 4 and
5. The thermodynamically favored products were obtained from the
imidazolidine intermediate through a ring-opening process (Sch. 2).
But compound 6 was special, and we obtained a ring-locking process
(Sch. 3).
In summary, N,N,N0-trisubstituted 2-methyl-ethylenediamine deri-
vatives 4, 5, and 6 were prepared by using a commercially available
heterocyclic compound, 4-methyl-2-imidazoline. The approach should be
wildly applicable for the preparation of other relevant N,N,N0-trisubstituted
2-methyl-ethylenediamine derivatives. Model compound 3 was treated with
a series of aromatic amines and research is being continued in our group.

A Convenient Synthesis of 1-Tosyl-3,4-Dimethyl Imidazolium Salt
3539
Scheme 2.
EXPERIMENTAL
Mass spectra were obtained on a JMS-D300 GC/MS spectrometer.
1
The H and 13C nmr were obtained on a JOELFX-60Q, Varian FT-80A or
Bruker AC-P 300 MHz, with TMS as an internal standard. Combustion
Scheme 3.

3540
Li et al.
analyses were performed on a Perkin-Elmer 240C or a MOD 1106 instrument.
Infrared spectra were obtained on a Shimadzu IR-1700 spectrometer. The
TLC were carried out on silica gel GF-254 20 ꢀ 20 cm2 plate. Melting
points were uncorrected. All reactions were performed under an inert atmos-
phere of nitrogen; all reagents and solvents were purified and dried as
required.
4-Methyl imidazoline (1): Ethyl formate (14.8 g, 0.2 mmol) was added
dropwise to 17.6 g (0.2 mmol) of 1,2-diaminopropane, the latter being
cooled in ice about 2 h. After having stirred for 1 h at room temperature,
the reaction mixture was heated and ethanol was distilled off. The resulting
mixture was heated at 1508C–1608C for 2 h. Then cooling, the mixture
was distilled under reduced pressure. Yield: 11.2 g (67%); boiling point
(bp) 100–1108/15 mm; 1H NMR (CDCl3): 1.12 (d, 3 H), 3.08 (m, 1 H),
3.65 (m, 1 H), 3.84 (m, 1 H), 4.17 (s, 1 H), 6.96 (s, 1 H).
1-Tosyl-4-methyl imidazoline (2): 4-Methyl imidazoline 1 (8.4 g,
0.1 mol) was dissolved in 20 mL dry dichloromethane at 08C, followed by
the addition of triethyl amine (10.1 g, 0.1 mol). To this solution was added
dropwise a solution of tosyl chloride (19.05 g, 0.1 mol) in 10 mL dichloro-
methane. The reaction mixture was stirred and warmed to room temperature
in an additional 1.5 h. The resulted solution was washed with 5% sodium
hydroxide solution (20 mL) and water (50 mL), and dried over anhydrous
sodium sulfate. Evaporation of dichloromethane in vacuo gave a crude
solid, while was recrystallized from anhydrous ethyl alcohol to yield
1
12.36 g (52%) of 2 as a white crystal, mp 53–558C. H NMR (CDCl3):
1.15 (d, 3 H), 2.44 (s, 3 H), 2.97 (t, 1 H), 3.53 (t, 1 H), 4.22 (m, 1 H), 7.34
(t, 3 H), 7.71 (d, 2 H) IR (KBr) cm21: 3284, 1652 (yC55N), 1598, 1494,
1436, 1359, 1163 (yC55N). MS m/e: 237.2([M-1]þ), 207, 149, 91. Anal.
calcd. for C11H14N2O2S: C, 55.44; H, 5.92; N, 11.76. Found C, 55.27;
H, 5.88; N, 11.69.
1-Tosyl-3,4-dimethyl imidazolium iodide (3): 1-Tosyl-4-methyl
imidazoline 2 (2.38 g, 10 mmol) and iodomethane (1.9 mL, 30 mmol) were
refluxed in 20 mL dry benzene for 2 h. A lot of solid was separated out.
Then cooled to room temperature, a precipitate was collected by filtration
and crystallized from ethyl alcohol to give 3.04 g (80%) of 3 as a white
1
crystal. mp 175.2–176.78C H NMR (CDCl3): 1.51 (d, 3 H), 2.46 (s, 3 H),
3.63 (s, 4 H), 4.33 (t, 1 H), 4.80 (s, 1 H), 7.45 (d, 2 H), 8.15 (d, 2 H)
9.72 (s, 1 H). IR (KBr) cm21: 3430, 1661 (yC55N), 1594, 1451, 1422,
1374, 1166 (yC55N). MS m/e: 253 ([M-HI]þ), 238, 155, 91. Anal. calcd.
for C12H17N2O2SI: C, 37.90; H, 4.51; N, 7.37. Found C, 38.04; H, 4.59;
N, 7.30.
N-Methyl-N-(2-dicyanovinyl)-N0-(p-toluenesulphonyl)-ethylenedia-
mine (4): Sodium hydride (43 mg, 1.8 mmol) was added into a solution of

A Convenient Synthesis of 1-Tosyl-3,4-Dimethyl Imidazolium Salt
3541
malononitrile (78 mg, 1.5 mmol) in 10 mL of dry tetrahydrofuran, which was
cooled in an ice-water bath. The reaction mixture was stirred for 30 minutes,
then the imidazolium 3 (380 mg, 1 mmol) was added and the mixture
was allowed to warm to room temperature for 2 h. Then the solution was
extracted with dichloromethane (3 ꢀ 30 mL), the combined organic layers
were washed with water and dried over anhydrous sodium sulfate. Evapor-
ation of dichloromethane in vacuo gave a crude solid, which was recrystal-
lized from anhydrous ethyl alcohol to yield 2.8 g (88%) of 4 as a white
1
crystal, mp 179.18C–180.48C. H NMR (CD3COCD3): 1.26 (d, 3 H), 2.42
(s, 3 H), 2.89 (s, 1 H), 3.12 (s, 4 H), 3.83 (s, 1 H), 7.25 (s, 1 H), 7.42
(d, 2 H), 7.74 (d, 2 H). IR (KBr) cm21: 3429 (m, NH), 2211 (s, CN),
1631, 1448, 1417, 1358, 1163 (yC55N). MS m/e: 318 ([M]þ), 238, 155,
91. Anal. calcd. for C15H18N4O2S: C, 56.58; H, 5.70; N, 17.60. Found C,
56.39; H, 5.70; N, 17.59.
N-Methyl-N-(2-dicyanovinyl)-N0-(p-toluenesulphonyl)-ethylenedia-
mine (5): Sodium hydride (43 mg, 1.8 mmol) was added into a solution of
nitromethane (91.5 mg, 1.5 mmol) in 10 mL of dry tetrahydrofuran, which
was cooled with an ice-water bath. The reaction mixture was stirred for
30 minutes, then the imidazolium 3 (380 mg, 1 mmol) was added and the
mixture was allowed to warm to room temperature for 1 h, then the solution
was extracted with dichloromethane (3 ꢀ 30 mL), the combined organic
layers were washed with water and dried over anhydrous sodium sulfate.
Evaporation of dichloromethane, a crude solid was yielded by column chro-
matography, yield: 0.302 g (96%) of 5 as a white crystal, mp 136–1388C;
1H NMR (CDCl3): 1.22 (d, 3 H), 2.43 (s, 3 H), 2.74 (s, 3 H), 3.01 (m, 2 H),
3.68 (m, 1 H), 6.17 (s, 1 H), 6.68 (d, 1 H), 7.33 (d, 2 H), 7.56 (d, 2 H),
8.17 (d, 2 H). IR (KBr) cm21: 3430, 1661 (yC55N), 1594, 1451, 1422,
1374, 1166 (yC55N). MS m/e: 253 ([M-HI]þ), 238, 155, 91. Anal. calcd.
for C13H19N3O4S: C, 49.84; H, 6.11; N, 13.41. Found C, 50.29; H, 6.29;
N, 13.78.
1-Carbethoxy-2-[20(4-methylbenzenesulphonyl)amine-10-methyl]amino
acrylic acid ethyl ester (6): Sodium hydride (43 mg, 1.8 mmol) was added
into a solution of ethyl malonate (240 mg, 1.5 mmol) in 10 mL of dry tetra-
hydrofuran, which was cooled with an ice-water bath. The reaction mixture
was stirred for 30 minutes, then the imidazolium 3 (380 mg, 1 mmol) was
added and the mixture was allowed to warm to room temperature for 5 h.
The filtrate was concentrated, and the residue was purified by column chro-
matography (silica gel, gradient chloroform, and methanol) of 6 as an oil,
1
yield: 0.325 g (79%). H NMR (CDCl3): 1.14 (m, 9 H), 2.36 (s, 3 H), 2.61
(s, 3 H), 2.92 (d, 2 H), 3.50 (m, 1 H), 4.11 (m, 5 H), 7.23 (d, 2 H), 7.68
(d, 2 H); IR (KBr) cm21: 3205(m), 1680(m), 1650, 1417, 1375, 1150
(yC55N); MS m/e: 355, 281, 267, 253, 225, 207, 155, 91, 73.

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Li et al.
ACKNOWLEDGMENTS
This work was supported by the National Natural Science Foundation of
China (20272034) and the Natural Science Foundation of Shanxi Province,
China (20041007 and 20041006).
Supporting information available: X-ray data for model compound
3 (CIF).
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A Convenient Synthesis of 1-Tosyl-3,4-Dimethyl Imidazolium Salt
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Received in Japan April 22, 2004