Synthesis and study of 1-aryl-1H-4,5-dihydroimidazoles

Article abstract of DOI:10.1055/s-2004-816011

An easy synthesis of 1-aryl-1H-4,5-dihydroimidazoles 1 by cyclocondensation of N-aryl-N′-formylethylenediamines 2 is described. Such precursors were synthesized by selective formylation of N-arylethylenediamines 3 with p-nitrophenyl formate. Cyclizations were performed using trimethylsilyl polyphosphate. Chemical properties of compounds 1, typical of amidine system, were studied. Reaction of 1 with methyl iodide leads to the corresponding 1-aryl-3-methyl-1H-4,5-dihydroimidazolium salts 5. Reduction of dihydroimidazoles 1 with sodium cyanoborohydride provides a convenient access to N-aryl-N′-methylethylenediamines 4.

Full text of DOI:10.1055/s-2004-816011

PAPER
851
Synthesis and Study of 1-Aryl-1H-4,5-dihydroimidazoles
S
ynthesi
s
s
and Stud
a
y of 1-Aryl
b
-1
H
-4,5-dihy
e
droimidazo
l
les Perillo,* M. Cristina Caterina, Julieta López, Alejandra Salerno
Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Junín 956 (1113), Buenos Aires, Argentina
Fax +541(1)49648250; E-mail: iperillo@ffyb.uba.ar
Received 13 January 2004
ric acid esters (PPE, PPSE) is described. This method is an
extension of that previously employed by us to obtain 1,2-
diaryl derivatives by cyclization of N-aryl-N¢-aroylethyl-
enediamines.10 The synthetic route from bromo-
Abstract: An easy synthesis of 1-aryl-1H-4,5-dihydroimidazoles 1
by cyclocondensation of N-aryl-N¢-formylethylenediamines 2 is de-
scribed. Such precursors were synthesized by selective formylation
of N-arylethylenediamines 3 with p-nitrophenyl formate. Cycliza-
tions were performed using trimethylsilyl polyphosphate. Chemical ethylamine is depicted in Scheme 1.
properties of compounds 1, typical of amidine system, were studied.
Reaction of 1 with methyl iodide leads to the corresponding 1-aryl-
3-methyl-1H-4,5-dihydroimidazolium salts 5. Reduction of dihy-
droimidazoles 1 with sodium cyanoborohydride provides a conve-
nient access to N-aryl-N¢-methylethylenediamines 4.
Key words: heterocycles, nitrogen, cyclization, reductions, alkyla-
tions
1H-4,5-Dihydroimidazoles 1 (2-imidazolines) are cyclic
amidines of pharmacological interest due to the properties
shown by some members, such as antihypertensive (ha-
lobenzyl-2-imidazolines),1 antihelminthic (2-alkenylimi-
dazolines),2 anti-inflamatory and analgesic (2,5-
diarylimidazolines).3 Other 1H-4,5-dihydroimidazoles
derivatives were studied as hypoglycemic agents.4 Bio-
logical effects were attributed to activation of three groups
of imidazoline receptors (I1, I2, I3).5 From a chemical point
of view, the synthesis and study of such compounds be-
came of interest because they are synthetic intermediates
in the preparation of pentagonal 1,3-diazaheterocycles6–8
and acyclic compounds carrying the ethylenediamine
structural unit.8–11 Imidazoline moiety was also employed
Scheme 1 (a) Arylamines; (b) p-nitrophenyl formate; (c) PPE, PPSE.
as a source of carbon units in transfer reactions.11,12
2-Substituted and 1,2-disubstituted 4,5-dihydroimida-
zoles were largely studied. Instead there are only scanty
reports on C2 unsubstituted analogs, most of them N-alkyl
derivatives. However, only one N-aryl derivative was re-
ported in the literature.13 These compounds were obtained
classically by condensation of 1,2-diaminoethanes and
formic acid derivatives such as ethyl formate,14 the corre-
sponding iminoether15 or ethyl orthoformate.6a As a
source of C2, hydrogen cyanide13 and triazine16 were also
employed. Alternative synthetic methods such as imida-
zolidine dehydrogenation,17 cyclization of N,N¢-
diformylethylenediamines18 and reaction of ethylenedi-
amines with formimines and sulfur19 were also reported.
Chemical properties of compounds 1, typical of the ami-
dine system, were studied: reduction with a nucleophilic
agent (sodium cyanoborohydride) and quaternization with
methyl iodide.
N-Arylethylenediamines 3a–f were obtained by aminoly-
sis of 2-bromoethylamine (hydrobromide) with aromatic
amines. This method presents advantages compared to
other aminoethylation reactions described in the litera-
ture.20 However, the procedure can not be employed for
arylamines containing electron acceptor substituents such
as ortho and para nitro groups. Compound 3g was ob-
tained from p-nitrochlorobenzene and ethylenediamine
according with literature procedure.21
In this work an easy synthesis of 1-aryl-1H-4,5-dihy-
droimidazoles 1 (Scheme 1) which involves ring closure
of N-aryl-N¢-formylethylenediamines 2 by polyphospho-
Formylation of N-arylethylenediamines was performed
with formic acid. However, reactions lead to a mixture of
N-aryl-N¢-formylethylenediamines 2 (50–70%) (Table 1)
and N-aryl-N,N¢-diformylethylenediamines (25–45%).
Yields depend on the aromatic substitution: diformylation
increased with the electron donor effect of the aryl substit-
uent. In order to increase formylation selectivity, p-nitro-
SYNTHESIS 2004, No. 6, pp 0851–0856
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Advanced online publication: 15.03.2004
DOI: 10.1055/s-2004-816011; Art ID: M00304SS
© Georg Thieme Verlag Stuttgart · New York

852
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PAPER
Table 1 Data for Products 2a–g
Producta
MS
Yieldb
(%)
1H NMR (CDCl3/TMS)
d, J (Hz)
m/z (M+)
2a
164
83
77
75
75
89
85
91
8.20 (s, 1 H, CHO), 7.20 (m, 2 Harom), 6.70 (t, 1 Harom J = 7.40), 6.60 (d, 2 Harom,
J = 7.60), 5.95 (br s, 1 H, NHCO), 3.87 (br s, 1 H NHAr), 3.45 (q, 2 H, J = 6.20,
CH2NHCHO), 3.15 (t, 2 H, J= 6.20, CH2NHAr)
2b
2c
2d
2e
2f
178
8.19 (s, 1 H, CHO), 7.01 (dd, 2 Harom, J = 6.41, 2.03), 6.56 (dd, 2 Harom, J = 6.41,
2.03), 6.15 (br s, 1 H, NHCHO), 3.85 (br s, 1 H, NHAr), 3.51 (q, 2 H, J = 6.15,
CH2NHCHO), 3.20 (t, 2 H, J = 6.15, CH2NHAr), 2.20 (s, 3 H, CH3)
178
8.15 (s, 1 H, CHO), 7.20 (m, 2 Harom), 6.71 (m, 2 Harom), 6.02 (br s, 1 H, NH-
CHO), 3.80 (br s, 1 H, NHAr), 3.47 (q, 2 H, J = 5.81, CH2NHCHO), 3.17 (t, 2
H, J = 5.81, CH2NHAr), 2.18 (s, 3 H, CH3)
206
8.19 (s, 1 H, CHO), 6.97 (s, 2 Harom), 6.12 (br s, 1 H, NHCHO), 3.90 (br s, 1 H,
NHAr), 3.50 (q, 2 H, J = 5.15, CH2NHCHO), 3.19 (t, 2 H, J= 5.15, CH2NHAr),
2.20 (s, 3 H, CH3), 2.16 (s, 6 H, CH3)
194
8.20 (s, 1 H, CHO), 6.76 (dd, 2 Harom, J = 8.80, 2.20), 6.55 (dd, 2 Harom, J = 8.80,
2.20), 6.10 (br s, 1 H, NHCHO), 3.79 (s, 3 H, CH3O), 3.55 (q, 2 H, J = 5.77,
CH2NHCHO), 3.35 (br s, 1 H, NHAr), 3.18 (t, 2 H, J = 5.77, CH2NHAr)
198, 200
209
8.12 (s, 1 H, CHO), 7.25 (d, 2 Harom, J = 8.78), 6.59 (d, 2 Harom, J = 8.78), 5.99
(br s, 1 H, NHCHO), 3.57 (q, 2 H, J = 5.80, CH2NHCHO), 3.35 (br s, 1 H,
NHAr), 3.24 (t, 2 H, J = 5.80, CH2NHAr)
2gc
8.20 (br s, 1 H, NH), 8.09 (s, 1 H, CHO), 8.01 (dd, 2 Harom, J = 10.10, 2.50), 7.40
(br s, 1 H, NH), 6.70 (dd, 2 Harom, J = 10.10, 2.50), 3.21 (m, 4 H, CH2CH2)
a Satisfactory microanalyses obtained: C 0.08, H 0.10, N 0.09.
b Pure products.
c Mp 157 °C. 1H NMR was recorded in DMSO-d6.
phenyl formate was employed; in this case yields higher
than 75% for all monoformyl derivatives 2 were obtained.
Cyclization of compounds 2 was initially carried out with
PPE (polyphosphate ester) which had been an appropriate
agent to obtain 1,2-diarylimidazolines.8,10 However,
yields did not exceed 40%. Better results (72–82% yields)
were obtained with trimethylsilyl polyphosphate (PPSE).
This aprotic cyclizing reagent has been previously em-
ployed in the synthesis of several types of heterocycles,
and specially for the synthesis of cyclic amidines.22,23
Compounds 1 (Table 2) proved to be highly unstable
(they easily undergo hydrolysis at room temperature, giv-
ing the formyl derivatives 2), which hampers their isola-
tion, purification and spectroscopic characterization.
Scheme 2
The final isolated product may arise either from direct re-
duction of the aminoimine in equilibrium with the
aminal24,25 or through an intermediary iminium ion arising
from imidazolidine ring opening in the reaction condi-
tions (Scheme 3). In this case, regioselectivity results
from the selective cleavage of the C2–NAr bond, with the
elimination of the less basic amine and formation of the
more stable iminium ion A. A similar mechanism has
been previously proposed by us in order to justify the
products obtained in the reduction of 1,3-disubstituted im-
idazolidines.8
In order to evaluate the 1H-4,5-dihydroimidazoles 1 as
potential precursors of cyclic and acyclic compounds car-
rying
the
ethylenediamine
structural
moiety
(NCH2CH2N), reactions resulting from C2 electrophilic
character (reduction) and to N3 nucleophilic properties
(quaternization) were studied (Scheme 2).
Treatment of 1a–g with sodium cyanoborohydride in eth-
anol at room temperature lead regiospecifically to the
asymmetric N,N¢-disubstituted ethylenediamines 4. The
reaction can be interpreted as the result of initial hydride
ion attack at the electrophilic C2, with formation of the
1H-4,5-Dihydroimidazoles 1 behave as good nucleo-
philes and may be easily N3-alkylated by reaction with
methyl iodide in dichloromethane at reflux giving the cor-
corresponding
(Scheme 3).
2,3-unsubstituted
imidazolidine
responding
1H-4,5-dihydroimidazolium
salts
5
(Scheme 2). They were isolated as stable solids, purified
Synthesis 2004, No. 6, 851–856 © Thieme Stuttgart · New York

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Synthesis and Study of 1-Aryl-1H-4,5-dihydroimidazoles
853
Table 2 Data for Products 1a–g
Producta
MS
Yieldb
(%)
1H NMR (CDCl3/TMS)
d, J (Hz)
m/z (M+)
1a
146
72
7.48 (s, 1 H, NCHN), 7.30–6.70 (m, 5 Harom), 3.61 (t, 2 H, J = 9.15, CH2), 3.52
(t, 2 H, J = 9.15, CH2)
1b
160
82
7.80 (s, 1 H, NCHN), 7.23 (dd, 2 Harom, J = 6.81, 2.70), 6.70 (dd, 2 Harom, J =
6.81, 2.70), 3.61 (t, 2 H, J = 8.91, CH2), 3.49 (t, 2 H, J = 8.91, CH2), 2.07 (s, 3
H, CH3)
1c
1d
1e
160
188
176
73
75
68
7.81 (s, 1 H, NCHN), 7.47–7.10 (m, 4 Harom), 4.10 (t, 2 H, J = 9.25, CH2), 3.61
(t, 2 H, J = 9.25, CH2), 2.10 (s, 3 H, CH3)
7.73 (s, 1 H, NCHN), 7.21 (s, 2 Harom), 4.15 (t, 2 H, J = 10.07, CH2), 3.54 (t, 2
H, J = 10.07, CH2), 2.21 (s, 3 H, CH3), 2.15 (s, 6 H, CH3)
7.45 (s, 1 H, NCHN), 7.15 (dd, 2 Harom, J = 8.50, 2.50), 6.90 (dd, 2 Harom, J =
8.50, 2.50), 3.79 (s, 3 H, OCH3), 3.67 (t, 2 H, J = 8.90, CH2), 3.51 (t, 2 H, J =
8.90, CH2)
1f
180, 182
191
69
75
7.83 (s, 1 H, NCHN), 7.32 (d, 2 Harom, J = 8.57), 6.89 (d, 2 Harom, J = 8.57), 3.56
(t, 2 H, J = 8.40, CH2), 3.49 (t, 2 H, J = 8.40, CH2)
1gc
8.20 (d, 2 Harom, J = 9.19), 8.10 (s, 1 H, NCHN), 7.19 (d, 2 Harom, J = 9.19), 3.95
(t, 2 H, J = 8.83, CH2), 3.71 (t, 2 H, J = 8.83, CH2)
a Satisfactory microanalyses obtained: C 0.11, H 0.09, N 0.13.
b Pure products.
c Hygroscopic solid.
tons. Maas spectra (EI) were recorded with a GC-MS Shimadzu
QP-1000 spectrometer operating at 20 eV. HRMS determinations
were performed on a VG ZAB-SEQ (VG Analytical, Manchester,
UK) hybrid tandem mass spectrometer of BeqQ geometry,
equipped with an electron impact ion source. TLC analyses were
carried out on aluminum sheets silica gel 60 F254. Column chroma-
tography was performed on silica gel 60 (0.063–0.200 mesh) with
typically 30–50 g of stationary phase per gram substance.
by recrystallization and spectroscopically characterized
(Table 3). Compounds 5 represent a potential source of
imidazolidines and N,N,N¢-trisubstituted ethylenedi-
amines.8,9
Melting points were determined with a Büchi capillary apparatus
1
and are uncorrected. H NMR spectra were recorded on a Bruker
MSL 300 MHz spectrometer using CDCl3 as the solvent unless oth-
erwise indicated. Standard concentration of the samples was 20 mg/
mL. Chemical shifts are reported in ppm (d) relative to TMS as an
internal standard. D2O was employed to confirm exchangeable pro-
N-(4-Nitrophenyl)ethylenediamine (3g) was described in the litera-
ture.21
Scheme 3
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854
I. Perillo et al.
PAPER
Table 3 Data for Products 5a–g
Producta
5a
Mp
(°C)
Yieldb
(%)
1H NMR (CDCl3/TMS)
d, J (Hz)
182
178
92
9.87 (s, 1 H, NCHN), 7.25 (m, 2 Harom), 7.15–7.20 (m, 3 Harom), 4.43 (t, 2 H,
CH2NAr, J = 11.00), 4.17 (t, 2 H, CH2NCH3, J = 11.00), 3.47 (s, 3 H, CH3)
5b
87
9.90 (s, 1 H, NCHN), 7.40–7.30 (m, 2 Harom), 7.20–7.10 (m, 2 Harom), 4.45 ( t, 2
H, J = 11.40, CH2NAr), 4.20 (t, 2 H, J = 11.40, CH2NCH3), 3.50 (s, 3 H, NCH3),
2.30 (s, 3 H, CH3Ar)
5c
168
175
89
86
8.90 (s, 1 H, NCHN), 7.50 (d, 2 Harom, J = 7.69), 7.30–7.10 (m, 4 Harom), 4.40–
4.20 (m, 4 H, CH2CH2), 3.40 (s, 3 H, NCH3), 2.40 (s, 3 H, CH3Ar)
5d
9.01 (s, 1 H, NCHN), 6.90 (s, 2 Harom), 4.40 (t, 2 H, J = 11.01, CH2NAr), 4.15
(t, 2 H, J = 11.01, CH2NCH3), 3.51 (s, 3 H, NCH3), 2.30 (s, 6 H, CH3), 2.20 (s,
3 H, CH3)
5e
5f
178
179
183
75
91
92
9.85 (s, 1 H, NCHN), 7.45 (dd, 2 Harom, J = 6.80, 2.31), 6.90 (dd, 2 Harom, J =
6.80, 2.31), 4.41 ( t, 2 H, J = 11.3, CH2NAr), 4.15 (t, 2 H, J = 11.3, CH2NCH3),
3.80 (s, 3 H, OCH3), 3.51 (s, 3 H, NCH3)
10.12 (s, 1 H, NCHN), 7.43 (d, 2 Harom, J = 9.22), 7.35 (d, 2 Harom, J = 9.22),
4.43 (t, 2 H, J = 11.2, CH2NAr), 4.17 (t, 2 H, J = 11.2, CH2NCH3), 3.51 (s, 3 H,
NCH3)
5g
9.91 (s, 1 H, NCHN), 7.90 (d, 2 Harom, J = 9.23), 7.50 (d, 2 Harom, J = 9.23), 4.30–
4.45 (m, 4 H, CH2CH2), 3.50 (s, 3 H, NCH3)
a Satisfactory microanalyses obtained: C 0.10, H 0.10, N 0.12.
b Pure products.
N-Arylethylenediamines 3 a–f; General Procedure
N-(2-Methylphenyl)ethylenediamine (3c)20b
A mixture of 2-bromoethylamine hydrobromide (2.05 g, 10 mmol)
and the corresponding arylamine (30 mmol) in toluene (40 mL) was
refluxed for 40 min. The precipitate was filtered and treated with
20% aq NaOH (30 mL) and the mixture was extracted with CH2Cl2
(3 × 30 mL). The organic layer was shaken with acetic/acetate buff-
er (pH 5.5, 20 mL) after which the aqueous layer was separated,
made alkaline with 20% aq NaOH (20 mL) and extracted with
CH2Cl2 (3 × 20 mL). The organic phases were combined, washed
with H2O, dried and filtered. The solvent was removed in vacuo and
the crude products were purified by column chromatography (ben-
zene–MeOH, 7:3 to 1:9).
Yield: 75%.
1H NMR: d = 7.10 (m, 2 Harom), 6.65 (m, 2 Harom), 4.70 (br s, 1 H,
NH), 3.25 (t, 2 H, J = 5.64 Hz, CH2NAr), 2.99 (t, 2 H, J = 5.64 Hz,
CH2NH2), 2.15 (s, 3 H, CH3), 2.01 (br s, 2 H, NH2).
HRMS: m/z calcd for C9H14N2: 150.1158; found: 150.1163.
N-(2,4,6-Trimethylphenyl)ethylenediamine (3d)
Yield: 86%; oil.
1H NMR: d = 6.95 (s, 2 Harom), 4.56 (br s, 1 H, NH), 3.42 (t, 2 H,
J = 5.47 Hz, CH2NAr), 2.93 (t, 2 H, J = 5.47 Hz, CH2NH2), 2.21 (s,
3 H, CH3), 2.17 (s, 6 H, CH3), 1.95 (br s, 2 H, NH2).
N-Phenylethylenediamine (3a)20b
Yield: 75%.
MS: m/z = 178 (M+.).
Anal. Calcd for C11H18N2: C, 74.11; H, 10.18; N, 15.71. Found: C,
74.13; H, 10.12; N, 15.68.
1H NMR: d = 7.15 (m, 2 Harom), 6.50 (m, 3 Harom), 4.15 (br s, 1 H,
NH), 3.45 (t, 2 H, J = 5.31 Hz, CH2NAr), 2.95 (t, 2 H, J = 5.35 Hz,
CH2NH2), 1.87 (br s, 2 H, NH2).
N-(4-Methoxyphenyl)ethylenediamine (3e)20b
Yield: 78%.
HRMS: m/z calcd for C8H12N2: 136.1001; found: 136.1005.
1H NMR: d = 6.80 (dd, 2 Harom, J1 = 6.69, J2 = 2.20 Hz), 6.60 (dd, 2
N-(4-Methylphenyl)ethylenediamine (3b)20b
Yield: 79%.
1H NMR: d = 7.00 (d, 2 Harom, J = 8.30 Hz), 6.56 (d, 2 Harom
H
arom, J1 = 6.69, J2 = 2.20 Hz), 4.70 (br s, 1 H, NH), 3.80 (s, 3 H,
OCH3), 3.15 (t, 2 H, J = 5.49 Hz, CH2NAr), 2.90 (t, 2 H, J = 5.49
Hz, CH2NH2), 2.02 (br s, 2H, NH2).
,
J = 8.30 Hz), 4.30 (br s, 1 H, NH), 3.17 (t, 2 H, J = 5.48 Hz,
CH2NAr), 2.94 (t, 2 H, J = 5.48 Hz, CH2NH2), 2.23 (s, 3 H, CH3),
1.60 (br s, 2 H, NH2).
HRMS: m/z calcd for C9H14N2O: 166.1107; found: 166.1113.
N-(4-Chlorophenyl)ethylenediamine (3f)
Yield: 81%; oil.
HRMS: m/z calcd for C9H14N2: 150.1158; found: 150.1151.
1H NMR: d = 7.10 (d, 2 Harom, J = 8.98 Hz), 6.54 (d, 2 Harom
,
J = 8.98 Hz), 4.30 (br s, 1 H, NH), 3.13 (t, 2 H, J = 5.48 Hz,
CH2NAr), 2.93 (t, 2 H, J = 5.48 Hz, CH2NH2), 1.65 (br s, 2 H, NH2).
MS: m/z = 170 and 172 (M+.).
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Synthesis and Study of 1-Aryl-1H-4,5-dihydroimidazoles
855
Anal. Calcd for C8H11ClN2: C, 56.31; H, 6.50; N, 16.42. Found: C,
56.40; H, 6.42; N, 16.55.
pearance of starting material was observed by TLC (benzene–
MeOH, 9:1). The solution was concentrated in vacuo and the solid
products were recrystallized from anhyd propan-2-ol (Table 3). MS
(IE) of compounds 5 showed thermal decomposition before frag-
mentation.
N-Aryl-N¢-formylethylenediamines 2a–g; General Procedure
p-Nitrophenyl formate (1.67 g, 10 mmol) was added in small por-
tions to a solution of the corresponding N-arylethylenediamine 3
(10 mmol) in anhyd THF (15 mL) with stirring on an ice bath. The
reaction was monitored by TLC (EtOAc). After complete disap-
pearance of the starting material, the solvent was removed in vacuo.
The crude products were washed with aq sat. NaHCO3 solution and
purified by columm chromatography (EtOAc) affording com-
pounds 2 as oils. Yields and spectroscopic data of compounds are
given in Table 1.
Acknowledgment
This work was supported by the Universidad de Buenos Aires and
by CONICET (Consejo Nacional de Investigaciones Científicas y
Técnicas).
References
Reaction of compounds 3 (10 mmol) with formic acid (40 mmol)
under reflux afforded a mixture of the corresponding compounds 2
(50–70%) and N-aryl-N,N¢-diformylethylenediamines (25–45%).
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(2) (a) Ishikawa, F. Chem. Pharm. Bull. 1980, 28, 1394.
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1999, 42, 1587; and references cited therein.
N-Aryl-1H-4,5-dihydroimidazoles 1a–g; General Procedures
Using PPSE: The corresponding N-aryl-N¢-formylethylenediamine
2 (0.5 g) was dissolved in a CH2Cl2 solution of PPSE (prepared ac-
cording the method of Imamoto,26 10 mL) and refluxed for 1 h. The
solution was cooled and extracted with H2O (3 × 20 mL). The aque-
ous phases were pooled and made alkaline with Na2CO3 to pH 9.
The aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The
combined organic layers were washed with H2O, dried (Na2SO4),
filtered and evaporated in vacuo affording compounds 1 as oils
(Table 2).
Using PPE: Reactions of compounds 2 with PPE27 in the same man-
ner as described for PPSE afforded compounds 1 (25–40% yield).
(5) Szabo, B. Pharmacol. Ther. 2002, 93, 1; and references cited
therein.
Reduction of 1-Aryl-1H-4,5-dihydroimidazoles; General Proce-
dure
(6) Dehydrogenation to imidazoles. Among others: (a) Martin,
P. K.; Matthews, H. R.; Rapaport, H.; Thyagarajan, G. J.
Org. Chem. 1968, 33, 3758. (b) Hughey, J. L.; Knapp, S.;
Schugar, H. Synthesis 1980, 489. (c) Klem, R. E.; Skinner,
H. F.; Walba, H.; Isensee, R. H. J. Heterocycl. Chem. 1970,
7, 403. (d) Matsuura, T.; Ito, Y.; Saito, I. Bull. Chem. Soc.
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(7) Jones, R. C. F.; Howard, K. J.; Snaith, J. S. Tetrahedron Lett.
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1992, 29, 1725; and references cited therein..
NaBH3CN (3.142 g, 0.05 mol) was added during 5 min to a solution
of the appropriate 1H-4,5-dihydroimidazole 1 (0.01 mol) in EtOH
(20 mL) keeping the mixture at r.t. When total transformation had
occurred (ca. 30 min), the suspension was extracted with CHCl3 (3
× 15 mL). The organic layers were pooled, washed with H2O, dried
and concentrated in vacuo affording compounds 4a–g which were
purified by columm chromatography. Compounds 4a,b,e,28 4f29 and
4g30 were described in the literature.
N-Methyl-N¢-(2-methylphenyl)ethylenediamine (4c)
Yield: 78%; oil.
(9) Salerno, A.; Ceriani, V.; Perillo, I. A. J. Heterocycl. Chem.
1997, 34, 709; and references cited therein.
1H NMR: d = 7.20 (m, 2 Harom), 6.60 (m, 2 Harom), 3.47 (t, 2 H,
J = 5.64 Hz, CH2NAr), 3.30 (br s, 1 H, HNAr), 2.79 (t, 2 H, J = 5.64
Hz, CH2NCH3), 2.43 (br s, 1 H, HNCH3), 2.35 (s, 3 H, NCH3), 2.18
(s, 3 H, CH3C6H4).
(10) Fernández, B. M.; Reverdito, A. M.; Paolucci, G. A.; Perillo,
I. A. J. Heterocycl. Chem. 1987, 24, 1717.
(11) Anderson, H. W.; Jones, R. C. F.; Saunders, J. J. Chem. Soc.,
Perkin Trans. 1 1986, 1995; and references cited therein.
(12) Pandit, U. K. Pure Appl. Chem. 1994, 66, 759; and
references cited therein.
MS: m/z = 164 (M+.).
(13) (a) Seefelder, M.; Jentzsch, W. Badische Anilin & Soda-
Fabrik A.-G., German Patent 1189998, 1965; Chem. Abstr.
1965, 63, 610. (b) Jentzsch, W.; Seefelder, M. Chem. Ber.
1965, 98, 1342.
(14) Bieraugel, H.; Plemp, R.; Hiemstra, H. C.; Pandit, U. K.
Tetrahedron 1983, 39, 3971.
Anal. Calcd for C10H16N2: C, 73.13; H, 9.82, N, 17.06. Found: C,
73.20; H, 9.74; N, 17.12.
N-Methyl-N¢-(2,4,6-trimethylphenyl)ethylenediamine (4d)
Yield: 81%; oil.
1H NMR: d = 6.90 (m, 2 Harom), 3.48 (t, 2 H, J = 5.20 Hz, CH2NAr),
3.32 (br s, 1 H, HNAr), 2.75 (t, 2 H, J = 5.20 Hz, CH2NCH3), 2.72
(s, 3 H, NCH3), 2.45 (br s, 1 H, NHCH3), 2.21 (s, 3 H, CH3C6H4).
(15) Vecerková, J.; Vecerek, B.; Chundela, B. Chem. Listy 1953,
47, 1680; Chem. Abstr. 1955, 49, 1019.
(16) (a) Grundmann, C.; Kreutzberger, A. J. Am. Chem. Soc.
1955, 77, 6559. (b) Grundmann, C.; Kreutzberger, A. US
Patent 2841585, 1958; Chem. Abstr. 1958, 52, 20211.
(17) Docker, T.; Frank, A.; Krug, H. Ger. Offen. 2728976, 1979;
Chem. Abstr. 1979, 90, 121603.
MS: m/z = 192 (M+.).
Anal. Calcd for C12H20N2: C, 74.95; H, 10.48, N, 14.57. Found: C,
74.77; H, 10.55; N, 14.44.
(18) Becke, F.; Paessler, P.; Swoboda, O. P. Ger. Offen. 1922802,
1970; Chem. Abstr. 1971, 74, 22840.
(19) Hagen, H.; Becke, F. Ger. Offen. 2040502, 1970; Chem.
Abstr. 1972, 76, 140862.
1-Aryl-3-methyl-1H-4,5-dihydroimidazolium Salts 5a–g; Gen-
eral Procedure
A solution of the appropriate compound 1 (3 mmol) in CH2Cl2 (10
mL) and MeI (10 mmol) was heated under reflux until the disap-
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856
I. Perillo et al.
PAPER
(20) (a) Poindexter, G. S.; Owens, D. A.; Dolan, P. L.; Woo, E. J.
Org. Chem. 1992, 57, 6257; and references cited therein.
(b) Fourneau, J.-P.; Lestrange, M. Y. Bull. Soc. Chim. Fr.
1947, 827.
(25) Göblyös, A.; Lázár, L.; Evanics, F.; Fülöp, F. Heterocycles
1999, 51, 2431; and references cited therein.
(26) Yokohama, M.; Yoshida, S.; Imamoto, T. Synthesis 1982,
591.
(21) Chung, T. F.; Wu, Y. M.; Cheng, C. H. J. Org. Chem. 1984,
49, 1215.
(27) Pollmann, W.; Schramm, G. Biochim. Biophys. Acta 1964,
80, 1.
(22) Hedrera, M. E.; Perillo, I. A. Trends Heterocycl. Chem.
2002, 8, 105.
(28) Salerno, A.; Caterina, C.; Perillo, I. A. Synth. Commun.
2000, 30, 3369.
(23) García, M. B.; Orelli, L. R.; Magri, M. L.; Perillo, I. A.
Synthesis 2002, 2687.
(29) Wright, W. B. Jr.; Brabander, H. J. J. Org. Chem. 1961, 26,
2120.
(24) It is well known that N-1 and/or N-3 unsubstituted
imidazolidines exhibit ring (imidazolidine)-chain (imine)
tautomerism,25 and usually both species can be
spectroscopically identified.
(30) Perillo, I. A.; Lamdan, S. J. Chem. Soc., Perkin Trans. 1
1975, 894.
Synthesis 2004, No. 6, 851–856 © Thieme Stuttgart · New York