Microwave assisted reactions of some azaheterocylic compounds

Article abstract of DOI:10.3390/molecules14010403

A fast, general, environmentally friendly and facile method for preparation of five- and six-membered ring diazaheterocylic salts under microwave irradiation is presented. The N-alkylation reactions of imidazole, pyrimidine, pyridazine and phthalazine hav

Full text of DOI:10.3390/molecules14010403

Molecules 2009, 14, 403-411; doi:10.3390/molecules14010403
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Microwave Assisted Reactions of Some Azaheterocylic
Compounds
Gheorghita Zbancioc, Vasilichia Bejan, Marian Risca, Costel Moldoveanu and Ionel I.
Mangalagiu *
“Al. I. Cuza” University of Iasi, Organic Chemistry Department, Bd. Carol 11, 700506 Iasi, Romania
* Author to whom correspondence should be addressed; E-mail: ionelm@uaic.ro.
Received: 23 November 2008; in revised form: 12 January 2009 / Accepted: 15 January 2009 /
Published: 15 January 2009
Abstract: A fast, general, environmentally friendly and facile method for preparation of
five- and six-membered ring diazaheterocylic salts under microwave irradiation is
presented. The N-alkylation reactions of imidazole, pyrimidine, pyridazine and phthalazine
have been studied. The microwaves remarkably accelerated these N-alkylations, the
reaction times decreased dramatically, the reaction conditions were milder, the consumed
energy decreased considerably and the amount of solvents used was reduced substantially.
Consequently, the microwave assisted alkylation of N-containing heterocycles could be
considered eco-friendly. In some cases, under MW irradiation the yields are also higher. A
comparative study of microwave vs. classical conditions (liquid solvents) has been done.
Twelve new diazaheterocylic salts of potential practical interest were obtained.
Keywords: Microwave N-alkylation; Imidazole; Pyrimidine; Pyridazine; Phthalazine.
Introduction
During the last decades microwave (MW) irradiation has became an increasingly valuable tool in
organic chemistry, since it is a versatile and facile technique applicable to a large variety of syntheses
[1-10, 18]. Thus, a large number of organic reactions can be carried out under MW irradiation to often
give higher yields than conventional methods after shorter reaction times and under milder conditions.
Furthermore, reactions under MW have the great advantage of using small amounts or no organic

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Molecules 2009, 14
solvents (‘solvent free’), thus such reactions are more environmentally friendly and generate less side
products. There have been several reports on the successful application of microwave (MW) activation
to the alkylation of N-containing heterocycles [1, 3-10]. Among the latter imidazole, pyrimidine,
pyridazine and phthalazine compounds are well known biologically active and medicinally potent
anticancer [11-14], anti-HIV [15, 16], antibacterial and antifungal [11, 17, 18], and antihypertensive
agents [11, 19]. Moreover, imidazolium salts are potent room temperature ionic liquids of current great
interest in industry [20, 21].
The aim of this work was to develop a new, efficient and general method for preparation of
diazaheterocyle salts derived from imidazole, pyrimidine, pyridazine and phthalazine using MW
irradiation.
Results and Discussion
In order to obtain the desired azaheterocylic salts, we performed the alkylation of some N-
heterocyles with five- (imidazole derivatives) and six-membered rings (pyrimidine, pyridazine and
phthalazine), under both classical heating and MW irradiation conditions.
Imidazolium salts were obtained in two steps. First we carried out the N-cyanoethylation of the
acidic nitrogen of imidazole derivatives (imidazole and benzimidazole) via Michael addition of
acrylonitrile. In the second step we carried out the quaternization of the second nitrogen atom with
iodoacetamide and methyl- or ethyl bromoacetate, respectively (Scheme 1).
Scheme 1. Reaction pathway for the synthesis of imidazolium salts.
O
N
Y
3.a. R= X= I; Y= NH2
b. R= X= Br; Y= OCH3
c. R= X= Br; Y= OC2H5
N
N
X
N
N
CN
N
H
1a
2a
CN
O
X
Y
CN
X
3.d. X= I; Y= NH2
e. X= Br; Y= OCH3
f. X= Br; Y= OC2H5
N
Y
N
N
X= I; Y= NH2
X= Br; Y= OCH3,
OC2H5
O
N
N
2b
N
1b
H
N
CN
CN
O
Y
N
3.g. R= X= I; Y= NH2
h. R= X= Br; Y= OCH3
i. R= X= Br; Y= OC2H5
N
CH3
2c
X
N
CH3
We also performed the quaternization of methyl imidazole with iodoacetamide, methyl- or ethyl
bromoacetate, respectively. Diazinium salts were also obtained via the quaternization reaction of
pyrimidine, pyridazine and phthalazine with the same reagents (Scheme 2).

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Molecules 2009, 14
Scheme 2. Reaction pathway for synthesis of diazinium salts.
O
N
N
7.a. X= I; Y= NH2
b. X= Br; Y= OCH3
c. X= Br; Y= OC2H5
N
N
Y
O
X
4
X
O
N
Y
N
8.a. X= I; Y= NH2
b. X= Br; Y= OCH3
c. X= Br; Y= OC2H5
N
X= I; Y= NH2
X= Br; Y= OCH3,
OC2H5
N
Y
X
5
R
N
R
N
N
N
9.a. X= I; Y= NH2
b. X= Br; Y= OCH3
c. X= Br; Y= OC2H5
O
Y
X
6. R= C6H4Clp
Under classical heating conditions, these reactions have some major disadvantages, including long
reaction times (3-41 h), high energy consumption and the need for large amounts of solvents, etc. For
this reason we decided to use microwave technology, a nonconventional method, for the syntheses.
The MW assisted reactions were carried out using a monomode reactor, under constant irradiation
power and by varying the temperature (the so-called “power control”). The best results were obtained
when we used 30% (for imidazole derivatives) and 20% (for diazine derivatives) of the full power of
the magnetron (800 W), respectively. Table 1 lists the optimized conditions we employed, under MW
irradiation as well as under classical heating.
Table 1. Syntheses of azaheterocyle salts under MW and classical heating conditions, in
liquid phase.
Classical
Microwaves
Compound
Reaction
time
20
Reaction
temp., oC
56
Yields, Reaction
Reaction
Yields,
%
92
87
94
82
86
88
88
87
91
89
92
94
78
89
86
74
81
80
%
92
84
92
60
59
87
88
70
90
86
91
94
74
89
83
70
68
66
time
temp., oC
56
3a. X=I;Y= NH2
10 min.
10 min.
10 min.
15 min.
15 min.
15 min.
10 min.
10 min.
10 min.
5 min.
3b. X=Br;Y= OCH3
3c. X=Br;Y= OC2H5
3d. X=I;Y= NH2
20
56
56
20
56
56
25
56
56
3e. X=Br;Y= OCH3
3f. X=Br;Y= OC2H5
3g. X=I;Y= NH2
25
56
56
25
56
56
20
56
56
3h. X=Br;Y= OCH3
3i. X=Br;Y= OC2H5
7a. X=I;Y= NH2
20
56
56
20
56
56
3 h
80
70
7b. X=Br;Y= OCH3
7c. X=Br;Y= OC2H5
8a. X=I;Y= NH2
4 h
80
5 min.
70
3 h
80
5 min.
70
24 h
32 h
24 h
32 h
41 h
32 h
r.t.
5 min.
65
8b. X=Br;Y= OCH3
8c.X=Br;Y= OC2H5
9a. X=I;Y= NH2
r.t.
5 min.
65
r.t
5 min.
65
112
112
112
10 min.
10 min.
10 min.
80
9b. X=Br;Y= OCH3
9c. X=Br;Y= OC2H5
80
80

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Molecules 2009, 14
A comparative analysis for the data obtained leads to the conclusion that the use of MW resulted in
a remarkable acceleration of the reactions, with the reaction times decreasing dramatically, from hours
to minutes (5 to 15 min.). Also, the reaction temperature decreased in the most cases by 10 to 30 oC, so
consequently, the consumed energy decreased considerably too. Moreover, the amount of solvents
used is at least three-fold less (see Experimental), so these reactions may be considered as
environmentally friendly. It was also of interest that, in some cases, under MW irradiation the yields
are higher, sometimes substantially (by almost 20 %). The structure of the compounds synthesized was
1
proven by elemental (C, H, N) and spectral analysis (IR, H-NMR, 13C-NMR, 2D-COSY, 2D-
HETCOR (HMQC), long range 2D-HETCOR (HMBC). All the elemental and spectral data are in
accordance with the proposed structures and are presented to the Experimental section.
Conclusions
We report herein a comparative study of the syntheses of diazaheterocylic salts (with five- and six-
membered rings) under microwave irradiation and by classical heating in liquid solvents. A fast,
general, environmentally friendly, and facile method for preparation of diazaheterocylic salts under
microwave irradiation is presented. The microwave irracdiation provided a remarkable rate of
acceleration for N-alkylation, and the reaction times decreased dramatically, the reaction conditions
were milder, the consumed energy decreased considerably and the amount of solvents used was
reduced substantially, and consequently, the microwave assisted alkylation of N-containing
heterocycles could be considered eco-friendly. In some cases, under MW irradiation the yields are also
higher, sometimes substantially (by almost 20 %). Twelve new diazaheterocylic salts – 3a-i and 9a-c –
of potential practical interest were obtained.
Experimental
General
All the reagents and solvents employed were of the best grade available and were used without
further purification. Melting points were determined using an Electrothermal apparatus and are
1
13
uncorrected. The H- and C-NMR spectra and two-dimensional 2D-COSY, 2D-HETCOR (HMQC),
long range 2D-HETCOR (HMBC) experiments were recorded on a Bruker Avance 400 DRX
spectrometer operating at 400/100 MHz. Chemical shifts are given in ppm (δ-scale), coupling
constants (J) in Hz. For the microwave irradiation we used a 800 W STAR SYSTEM-2 monomode
reactor (CEM Corporation). The microanalyses were in satisfactory agreement with the calculated
values: C, ± 0.15; H, ± 0.10; N, ± 0.30.
General procedure for synthesis of imidazolium salts 3 under classical heating
Imidazole derivatives 2 (10 mmol) were dissolved in dry acetone (30 mL). A solution of
alkylbromoacetate or iodoacetamide (12 mmol) in dry acetone (10 mL) was added dropwise, under
stirring. The reaction mixture was then refluxed on an oil bath for 20 h (imidazole derivatives) or 25 h

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Molecules 2009, 14
(benzimidazole). The obtained salt was filtered under vacuum, washed with diethyl ether (5 mL) and
then purified by recrystallization from an appropriate solvent.
General procedure for syntheses of diazine salts 7-9 under classical heating
Diazine derivatives (10 mmol) were dissolved in benzene (2 mL, for 7), methanol (10 mL, for 8) or
toluene (10 mL, for 9). A solution of alkylbromoacetate or iodoacetamide (12 mmol), in
benzene/methanol/toluene (30 mL) was added dropwise, under stirring. The reaction mixture was then
refluxed for the appropriate period of time (Table 1). The obtained salts were filtered off, washed
twice with the solvent used (10 mL) and then purified by recrystallization from an appropriate solvent.
General procedure for syntheses of imidazolium (3) and diazine salts (7-9) under MW irradiation
Caution! It is hazardous to rapidly heat reactions under microwave irradiation. Therefore, caution
should be exercised when conducting reactions of this type.
Alkylbromoacetate or iodoacetamide [12 mmol, in 15 mL solvent (acetone for imidazole 2, benzene
for 7, methanol for 8, toluene for 9)] was placed in the reaction vessel (Pyrex glass or quartz; for
parallel synthesis both cells of the STAR reactor could be used, in which case the irradiation power of
reactor has to be double). Imidazole or diazine derivative (10 mmol) was then added. The tubes are
then placed in the microwave cell and heated for the appropriate time (Table 1). Stirring of the reaction
mixture is desirable. If a stirring device is not available it can be replaced with nitrogen continuously
bubbled into the reaction system. Once the heating cycle is complete, the tube was cooled to ambient
temperature, removed from the reactor, and the cycloimmonium salts were filtered off, then processed
as indicated under classical heating, above.
1-(Carbamoylmethyl)-3-(2-cyanoethyl)-3-H-imidazol-1-ium iodide (3a). Orange crystals, mp = 164-
1
166°C; H-NMR (DMSO-D6): 3.26-3.23 (t, J = 6.4 Hz, 2H, CH2: α-cyano), 4.58-4.55 (t, J = 6.4 Hz,
2H, CH2: β-cyano), 5.02 (s, 2H, CH2: α-C=O), 7.52 (s, 1H, NH, Hb), 7.77-7.76 (d, J = 1.6 Hz, 1H, CH:
H-5), 7.83 (s, 1H, NH, Ha), 7.85-7.84 (d, J = 1.6 Hz, 1H, CH: H-4), 9.23 (s, 1H, CH: H-2); 13C-NMR
(DMSO-D6): 18.68 (C, CH2: α-cyano), 44.44 (C, CH2: β-cyano), 50.62 (C, CH2: α-C=O), 117.59
(CN), 121.67 (C-4), 124.25 (C-5), 137.60 (C-2), 166.44 (C, C=O).
1-(2-cyanoethyl)-3-(2-methoxy-2-oxoethyl)-1H-imidazol-3-ium bromide (3b). White crystals, mp =
1
129-130°C; H-NMR (DMSO-D6): 3.34-3.31 (t, J = 6.4 Hz, 2H, CH2: α-cyano), 3.75 (s, 3H, OCH3),
4.67-4.64 (t, J = 6.4 Hz, 2H, CH2: β-cyano), 5.42 (s, 2H, CH2: α-C=O), 7.91 (s, 1H, CH: H-4), 8.02 (s,
1H, CH: H-5), 9.43 (s, 1H, CH: H-2); 13C-NMR (CDCl3): 18.69, (C, CH2: α-cyano), 44.56 (C, CH2: β-
cyano), 49.66 (C, CH2: α-C=O), 52.81 (C, OCH3), 117.57 (CN), 122.17 (C-5), 124.13 (C-4), 137.66
(C-2), 167.13 (C, C=O).
1
1-(2-Cyanoethyl)-3-(2-ethoxy-2-oxoethyl)-1H-imidazol-3-ium bromide (3c). Yellow oil; H-NMR
(DMSO-D6): 1.23-1.20 (t, J = 7.2 Hz, 3H, CH3), 3.32-3.29 (t, J = 6.4 Hz, 2H, CH2: α-cyano), 4.21-
4.16 (q, J = 7.2 Hz, 2H, OCH2), 4.66-4.62 (t, J = 6.4 Hz, 2H, CH2: β-cyano), 5.38 (s, 2H, CH2: α-

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Molecules 2009, 14
C=O), 7.91-7.90 (d, 1H, J = 1.2 Hz, CH: H-5), 8.02-8.01 (d, 1H, J = 1.2 Hz, CH: H-4), 9.44 (s, 1H,
CH: H-2); 13C-NMR (DMSO-D6): 13.93 (C, CH3), 18.79, (C, CH2: α-cyano), 44.66 (C, OCH2), 49.80
(C, CH2: β-cyano), 61.95 (C, CH2: α-C=O), 117.66 (CN), 122.19 (C-4), 124.18 (C-5), 137.76 (C-2),
166.67 (C, C=O).
1-(Carbamoylmethyl)-3-(2-cyanoethyl)-3-H-benzo[d]imidazol-1-ium iodide (3d). Yellow crystals, mp
= 167-169°C; 1H-NMR (DMSO-D6): 3.32-3.29 (t, J = 6.4 Hz, 2H, CH2: α-cyano), 4.95-4.92 (t, J = 6.4
Hz, 2H, CH2: β-cyano), 5.34 (s, 2H, CH2: α-C=O), 7.75-7.70 (m, 2H, H-5, H-6), 7.96-7.92 (m, 3H, H-
4, H-7, NHb), 8.20 (s, 1H, NH, Ha), 9.83 (s, 1H, CH, H-2); 13C-NMR (DMSO-D6): 18.11 (C, CH2: α-
cyano), 42.40 (C, CH2: β-cyano), 48.38 (C, CH2: α-C=O), 113.80 (C-7), 113.84 (C-4), 117.87 (CN),
126.73 (C-6), 126.96 (C-5), 130.49 (C-7a), 131.61 (C-3a), 143.73 (C-2), 166.32 (C, C=O).
1-(2-cyanoethyl)-3-(2-methoxy-2-oxoethyl)-1H-benzo[d]imidazol-3-ium bromide (3e). White crystals,
1
mp = 161-163°C; H-NMR (DMSO-D6): 3.41-3.38 (t, J = 6.8 Hz, 2H, CH2: α-cyano), 3.78 (s, 3H,
OCH3), 5.05-5.02 (t, J = 6.8 Hz, 2H, CH2: β-cyano), 5.77 (s, 2H, CH2: α-C=O), 7.75-7.73 (m, 2H, H-
5, H-6), 8.14-8.12 (dd, J = 4.4 Hz, J = 2.4 Hz, 1H, CH: H-7), 8.31-8.28 (dd, J = 4.0 Hz, J = 1.6 Hz,
13
1H, CH: H-4), 10.08 (s, 1H, CH: H-2); C-NMR (DMSO-D6): 18.14, (C, CH2: α-cyano), 42.57 (C,
CH2: β-cyano), 47.67 (C, CH2: α-C=O), 53.92 (C, OCH3), 113.99 (C-4), 114.10 (C-7), 117.77 (CN),
126.83 (C-6), 127.02 (C-5), 130.35 (C-7a), 131.29 (C-3a), 143.72 (C-2), 166.86 (C, C=O).
1-(2-Cyanoethyl)-3-(2-ethoxy-2-oxoethyl)-1H-benzo[d]imidazol-3-ium bromide (3f). White crystals,
1
mp = 157-158°C; H-NMR (DMSO-D6): 1.27-1.24 (t, J = 7.2 Hz, 3H, CH3), 3.38-3.35 (t, J = 6.4 Hz,
2H, CH2: α-cyano), 4.26-4.21 (q, J = 7.2 Hz, 2H, OCH2), 5.02-4.99 (t, J = 6.4 Hz, 2H, CH2: β-cyano),
5.72 (s, 2H, CH2: α-C=O), 7.77-7.71 (m, 2H, H-5, H-6), 8.11-8.09 (dd, J = 5.2 Hz, J = 2.4 Hz, CH: H-
13
7), 8.28-8.26 (dd, 1H, J = 5.2 Hz, J = 2.4 Hz, CH: H-4), 10.00 (s, 1H, CH: H-2); C-NMR (DMSO-
D6): 13.94 (C, CH3), 18.12, (C, CH2: α-cyano), 42.56 (C, OCH2), 47.69 (C, CH2: β-cyano), 62.03 (C,
CH2: α-C=O), 113.99 (C-7), 114.08 (C-4), 117.79 (CN), 126.87 (C-6), 127.06 (C-5), 130.40 (C-7a),
131.35 (C-3a), 143.75 (C-2), 166.67 (C, C=O).
1
1-Carbamoylmethyl-3-methyl-3-H-imidazol-1-ium iodide (3g). Yellow crystals, mp = 186-188°C; H-
NMR (DMSO-D6): 3.90 (s, 3H, CH3: NCH3), 4.98-4.95 (s, 2H, CH2: α-C=O), 7.52 (s, 1H, NH, Hb),
7.70 (s, 2H, H-4, H-5), 7.83 (s, 1H, NH, Ha), 9.08 (s, 1H, CH: H-2); 13C-NMR (DMSO-D6): 35.88 (C,
NCH3), 50.42 (C, CH2: α-C=O), 122.86 (C-5), 123.72 (C-4), 137.62 (C-2), 166.44 (C, C=O).
1-Methyl-3-(2-methoxy-2-oxoethyl)-1H-imidazol-3-ium bromide (3h). White crystals, mp = 135-
1
136°C; H-NMR (CDCl3): 3.75 (s, 3H, OCH3), 3.97 (s, 3H, NCH3), 5.42 (s, 2H, CH2: α-C=O), 7.87-
13
7.86 (m, 2H, H-4, H-5), 9.33 (s, 1H, CH: H-2); C-NMR (CDCl3, δ): 35.97 (C, NCH3), 49.42 (C,
CH2: α-C=O), 52.78 (C, OCH3), 123.28 (C-5), 123.55 (C-4), 137.54 (C-2), 167.29 (C, C=O).
1
1-Methyl-3-(2-ethoxy-2-oxoethyl)-1H-imidazol-3-ium bromide (3i). Yellow oil; H-NMR (CDCl3):
1.32-1.28 (t, J = 7.2 Hz, 3H, CH3), 4.10 (s, 3H, NCH3), 4.28-4.23 (q, J = 7.2 Hz, 2H, OCH2), 5.47 (s,
2H, CH2: α-C=O), 7.75-7.74 (d, J = 3.2 Hz, CH: H-5), 7.83-7.82 (d, J = 3.2 Hz, CH: H-4), 9.78 (s, 1H,

409
Molecules 2009, 14
CH: H-2); 13C-NMR (CDCl3): 14.12 (C, CH3), 36.94 (C, NCH3), 50.32 (C, OCH2), 62.86 (C, CH2: α-
C=O), 123.45 (C-5), 124.04 (C-4), 137.84 (C-2), 166.67 (C, C=O).
1
1-Ethoxycarbonylmethyl-pyridazin-1-ium bromide (7c). White crystals, mp = 160-161°C; H-NMR
(CDCl3): 1.36-1.33 (t, J = 7.2 Hz, 3H, CH3), 4.36-4.30 (q, J = 7.2 Hz, 2H, OCH2), 6.19 (s, 2H, CH2: α-
C=O), 8.65 (m, 1H, CH: H-4), 8.96 (m, 1H, CH: H-5), 9.44-9.43 (d, J = 6.0 Hz, 1H, CH: H-3), 10.96-
13
10.95 (d, J = 6.0 Hz, 1H, CH: H-6); C-NMR (CDCl3): 14.04 (C, CH3), 63.67 (C, OCH2), 65.30 (C,
CH2: α-C=O), 136.39 (C-5), 137.71 (C-4), 151.96 (C-6), 153.96 (C-3), 164.34 (C, C=O).
1
2-Ethoxycarbonylmethyl-phthalazin-2-ium bromide (8c). Yellow crystals, mp = 144-145°C; H-NMR
(CDCl3): 1.37-1.34 (t, J = 7.2 Hz, 3H, CH3), 4.37-4.32 (q, J = 7.2 Hz, 2H, OCH2), 6.04 (s, 2H, CH2: α-
C=O), 8.39-8.35 (td, J = 8.4 Hz, J = 1.2 Hz, 1H, CH: H-6), 8.50-8.46 (td, J = 8.4 Hz, J = 1.2 Hz, 1H,
CH: H-7), 8.60-8.58 (d, J = 7.6 Hz, 1H, CH: H-5), 8.85-8.83 (d, J = 7.6 Hz, 1H, CH: H-8), 9.88 (s, 1H,
CH: H-4), 11.78 (s, 1H, CH: H-1); 13C-NMR (CDCl3): 14.02 (C, CH3), 63.49 (C, CH2: α-C=O), 63.66
(CH2), 127.39 (C-8a), 128.04 (C-4a), 128.20 (C-8), 131.43 (C-7), 136.54 (C-5), 140.07 (C-4), 153.85
(C-1), 164.80 (C, C=O).
1-Carbamoylmetyl-4-(4-chlorophenyl)-pyrimidin-1-ium iodide (9a). Yellow crystals, mp = 123-125°C;
1H-NMR (CDCl3): 5.10-5.07 (s, 2H, CH2: α-C=O), 7.52-7.50 (d, J = 8.4 Hz, 2H, 2CH: H-3’), 7.85 (s,
1H, NHb), 8.09 (s, 1H, NHa), 8.32-8.30 (d, J = 8.4 Hz, 2H, 2CH: H-2’), 8.76-8.74 (d, J = 6.0 Hz, 1H,
13
CH: H-5), 9.77-9.76 (d, J = 6.0 Hz, 1H, CH: H-6), 9.91 (s, 1H, CH: H-2); C-NMR (CDCl3): 56.49
(CH2), 118.04 (C-5), 130.26 (C-2’), 130.57 (C-4’), 130.98 (C-3’), 131.32 (C-1’), 153.15 (C-6), 153.83
(C-2), 167.72 (C-4), 167.78 (C, C=O).
4-(4-Chlorophenyl)-1-methoxycarbonylmethyl-pyrimidin-1-ium bromide (9b). Pink crystals, mp =
102-104°C; 1H-NMR (CDCl3): 3.78 (s, 3H, CH3), 6.18 (s, 2H, CH2: α-C=O), 7.46-7.44 (d, J = 8.4 Hz,
2H, 2CH: H-3’), 8.25-8.23 (d, J = 8.4 Hz, 2H, 2CH: H-2’), 8.74-8.72 (d, J = 6.0 Hz, 1H, CH: H-5),
13
9.75-9.74 (d, J = 6.0 Hz, 1H, CH: H-6), 9.89 (s, 1H, CH: H-2); C-NMR (CDCl3): 54.05 (C, CH3),
57.73 (CH2), 118.11 (C-5), 130.28 (C-2’), 130.60 (C-4’), 131.01 (C-3’), 131.34 (C-1’), 153.16 (C-6),
153.85 (C-2), 167.74 (C-4), 168.83 (C, C=O).
4-(4-Chlorophenyl)-1-ethoxycarbonylmethyl-pyrimidin-1-ium bromide (9c). Pink crystals, mp = 114-
1
116°C; H-NMR (CDCl3): 1.36-1.33 (t, J = 7.2 Hz, 3H, CH3), 4.36-4.31 (q, J = 7.2 Hz, 2H, OCH2),
6.19 (s, 2H, CH2: α-C=O), 7.48-7.46 (d, J = 8.4 Hz, 2H, 2CH: H-3’), 8.26-8.24 (d, J = 8.4 Hz, 2H,
2CH: H-2’), 8.76-8.74 (d, J = 6.0 Hz, 1H, CH: H-5), 9.75-9.74 (d, J = 6.0 Hz, 1H, CH: H-6), 9.90 (s,
13
1H, CH: H-2); C-NMR (CDCl3): 14.04 (C, CH3), 63.51 (C, CH2: α-C=O), 57.77 (CH2), 118.14 (C-
5), 130.34 (C-2’), 130.61 (C-4’), 131.05 (C-3’), 131.37 (C-1’), 153.18 (C-6), 153.86 (C-2), 167.78 (C-
4), 168.87 (C, C=O).

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Molecules 2009, 14
Acknowledgements
This work was financially supported by the Romanian Ministry of Education and Research, grant
C.N.C.S.I.S., TD, No. 12/2008.
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Sample Availability: Samples of all prepared compounds are available from the authors.
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