Synthesis and crystal structure characterization of two new antibacterial agents: 5-[1-(2,3- and 2,4-dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidines

Article abstract of DOI:10.1002/jhet.5570400106

The synthesis of 5-[1-(2,3-dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine (4a) and 5-[1-(2,4- dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine (4b) is described. These compounds were prepared by chlorination of the corresponding 5-substituted barbituric acids obtained by treatment of the 5-benzylidenebarbituric acids with benzylzinc bromide in the preceding step. These new trichloropyrimidines belong to a series of pyrimidine derivatives which show in vitro antibacterial activity against the undesirable human bacterial flora of the axilla and foot. The characterization of these compounds were performed by spectroscopy and X-ray structure determination. Compounds 4a and 4b crystallize in the monoclinic system. In the crystal of 4a there are two conformers A and B both of which are the same type of conformation, and are different from that found in the structure of 4b. The crystal cohesion results from numerous very week Van der Waals interactions.

Full text of DOI:10.1002/jhet.5570400106

Jan-Feb 2003
Synthesis and Crystal Structure Characterization of two new
Antibacterial Agents: 5-[1-(2,3- and 2,4-Dichlorophenyl)-2-
phenylethyl]-2,4,6-trichloropyrimidines
51
H. Allouchi [a], Y. Fellahi [b], C. Hébert [b], C. Courseille [c] and Y. Frangin [b]
[a] Laboratoire de Chimie Physique - PIMIR E.A. 2098, Faculté des Sciences Pharmaceutiques, 31 avenue
Monge, 37200 Tours, France.
[b] Département de Chimie, Faculté des Sciences et Techniques, Parc de Grandmont, Université François
Rabelais, 37200 Tours, France
[c] Unité de Biophysique Structurale, UMR 5471-CNRS, Avenue des Facultés, Bâtiment de Biologie Végétale,
33405 Talence, France.
Received May 6, 2002
The synthesis of 5-[1-(2,3-dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine (4a) and 5-[1-(2,4-
dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine (4b) is described. These compounds were pre-
pared by chlorination of the corresponding 5-substituted barbituric acids obtained by treatment of the 5-ben-
zylidenebarbituric acids with benzylzinc bromide in the preceding step. These new trichloropyrimidines
belong to a series of pyrimidine derivatives which show in vitro antibacterial activity against the undesirable
human bacterial flora of the axilla and foot. The characterization of these compounds were performed by
spectroscopy and X-ray structure determination. Compounds 4a and 4b crystallize in the monoclinic system.
In the crystal of 4a there are two conformers A and B both of which are the same type of conformation, and
are different from that found in the structure of 4b. The crystal cohesion results from numerous very week
Van der Waals interactions.
J. Heterocyclic Chem., 40, 51 (2003).
The synthesis of pyrimidines has attracted the attention
of product 3a or 3b if three molecular equivalents of
organozinc reagent 2 were used. Compounds 3a and 3b
were purified by sodium hydroxide treatment before use in
trichloropyrimidine synthesis. The reaction yielded 70 %
of chemists because of their potential biological properties.
Over the last few years there has been an increased interest
for pyrimidine derivatives having antibacterial activity. In
the scope of our research, we have described in a previous
report the synthesis and the antibacterial activity of 5-(1,2-
diarylethyl)-2,4,6-trichloropyrimidines [1]. Among these
compounds, 5-[1-(4-chlorophenyl)-2-phenylethyl]-2,4,6-
trichloropyrimidine was the most active against the unde-
sirable human bacteria of both the foot and the axilla. In
continuation with our research work, 5-[1-(2,3-
dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine
(4a) and 5-[1-(2,4-dichlorophenyl)-2-phenylethyl]-2,4,6-
trichloropyrimidine (4b) were synthesized according to the
previously described method [1,2], with the aim to study
their crystal structures and their potential antibacterial
activity. Compounds 4a and 4b were characterized by the
usual spectroscopic techniques and by X-ray structure
analysis.
The synthetic method for preparing compounds 4a and
4b is shown in Scheme 1. The precursors of trichloropy-
rimidines 4a and 4b were barbituric acids 3a and 3b
respectively. Compounds 3a and 3b were obtained follow-
ing 1,4-addition of benzylzinc bromide (2) to the corre-
sponding benzylidenebarbituric acids 1a and 1b. Products
1a and 1b were easily prepared by condensing barbituric
acid with 2,3-dichlorobenzaldehyde and 2,4- dichloroben-
zaldehyde according to a method described with benzalde-
hyde [3]. In our previous paper [1], we proved that the
organozinc reagent 2 also undergoes hydrogen-metal
exchange with both NH sites of the benzylidenebarbituric
acids. The reaction therefore only led to substantial yields

52
H. Allouchi, Y. Fellahi, C. Hébert, C. Courseille and Y. Frangin
Vol. 40
of barbituric acid 3a and 81 % of barbituric acid 3b. The
reaction of the mixture of phosphorus oxychloride and
phosphorus pentachloride with barbituric acids 3a and 3b
according to the procedure of Gershon [4], gave the corre-
sponding 2,4,6-trichloropyrimidines 4a and 4b, which
were purified first by sodium hydroxide treatment to
remove the residual starting material 3a or 3b. The purity
was checked on the basis of their elution profile in a capil-
lary gas chromatography procedure. Gas chromatography
was coupled with a mass spectrometer to analyse com-
pounds 4a and 4b. Synthesis yielded 52 % of compound
4a and 64 % of compound 4b.
for 3b two singlets (8.33 and 8.55 ppm) assigned to the two
NH protons. The tertiary proton CH of the ethyl chain gave
a multiplet at 4.72 ppm for 3a and at 4.54 ppm for 3b. As
expected, the characteristic signals of the barbituric acids 3
1
were not observed in the H nmr spectra of the correspond-
1
ing trichloropyrimidines 4. Moreover, the H nmr signals of
the ethyl chain was modified. In particular, the tertiary pro-
ton exhibited a triplet for 4a (5.10 ppm with a coupling con-
3
stant J = 8.15 Hz) and for 4b (5.17 ppm with a coupling
3
constant J = 8.2 Hz) while the two protons of the methyl-
ene group gave a doublet for 4a (3.48 ppm with the cou-
3
pling constant J = 8.15 Hz) and for 4b (3.59 ppm with a
1
3
H nmr analysis at 200MHz of 5-substitutedbarbituric
coupling constant J = 8.2 Hz). The downfieldshift of the
acids displayed for 3a two singlets (7.97 and 8.17 ppm) and
tertiary proton resonance for trichloropyrimidines 4 com-
Table 1
Crystal Data, Data Collection and Structure Refinement for Compounds 4a and 4b
Compound 4a
Compound 4b
Crystal Data
Formula
Molecular weight (g.mol )
Temperature (K)
Wavelength (Å)
Crystal system
Space group
Z
C
H
Cl N
C
H
Cl N
18 11
5
2
18 11 5 2
-1
432.54
298
1.54178
monoclinic
P2 /c
432.54
298
1.54178
monoclinic
P2 /n
1
1
8
4
Unit cell dimensions
a (Å)
b (Å)
15.702(1)
13.276(2)
17.726(2)
92.58(1)
3691.3(7)
1.557
11.910(2)
13.065(1)
12.985(2)
110.91(1)
1886.4(4)
1.523
c (Å)
β (°)
3
Volume of cell(Å )
-3
Calculated density (g.cm )
F(000)
1744
7.189
872
7.035
-1
Absorption coefficient (mm )
Data Collection
Scan mode
ω-2θ
ω-2θ
Absorption correction mode
Limiting indices
ψ scan
ψ scan
h
k
/h
0/17
0/14
0/13
0/12
min max
/k
min max
l
/l
-19/19
-12/12
min max
Reflections collected
4675
60
1894
60
Limit of collection θ
Refinement
(°)
max
2
Refinement method
Parameters
On F
453
On F
227
Final R indices [I>2σ(I)]
R = 0.0574
wR = 0.1315
1.153
R = 0.0253
wR = 0.0653
1.092
Goodness-of-fit
Weighting factor
2
2
2
2
2
2
1/[σ (F )+(0.0130P) +8.1397P]
1/[σ (F )+(0.0271P) +1.1801P]
o
o
2
2
2
2
where P=(F +2F )/3
where P=(F +2F )/3
o c
o
c
Extinction coefficient
8.4(7)
0.0031(2)
-3
∆r / ∆r
(e.Å )
-0.407 / 0.493
0.029
-0.152 / 0.147
<0.001
min
max
(∆/r)
max

Jan-Feb 2003
Synthesis and Crystal Structure Characterization of two new Antibacterial Agents
53
pared to their barbituric acid precursors 3 characterized the
out-magnetic anisotropy effect of the pyrimidine ring of the
compounds 4. The mass spectrum (electronic ionization at
70 eV) of compounds 4a and 4b gave five molecular peaks
at m/z 430, 432, 434, 436 and 438 due to the presence of the
isotopes 35 and 37 of chlorine in the molecular formula
C
H Cl N . For the same reason, the fragment
18 11 5 2
+
(C H Cl N ) resulting from loss of the benzyl group was
11
4
5 2
assigned to four peaks at m/z 339, 341, 343 and 345.
For crystal structure analysis, the crystal data, the data
collection conditions and the refinement last indexes are
given in Table 1.
The molecular conformation, atomic labeling of non-
hydrogen atoms and ellipsoid representation [6] are shown
in Figure 1 for the two conformers A and B of 4a (there are
two independent molecules per asymmetric unit in the
Figure 2. ORTEP View of compound 4b. Thermal ellipsoids are drawn at
the 20% probability level.
Table 2
Significative Torsion Angles (°) for Compounds 4a and 4b
Compound 4a
Compound 4b
Conf. A
trans [a]
trans
Conf. B
166.3(8)
trans
C3-C4-C7-C8
C4-C7-C8-C9
C4-C7-C15-C16
C7-C8-C9-C10
-167.4(3)
168.8(3)
-128.0(3)
92.4(3)
-50.4(12)
87.7(10)
-55.0(11)
-91.5(11)
[a] Differing by less than 10° from the trans conformation.
because the Van der Waals intermolecular interactions are
very weak in the crystals.
Figure 1. ORTEP View of compound 4a: conformers A and B. Thermal
ellipsoids are drawn at the 20% probability level.
Preliminary pharmacological results were quite different
since compounds 4a and 4b demonstrated a better antibac-
terial activity than 5-[1-(4-chlorophenyl)-2-phenylethyl]-
2,4,6-trichloropyrimidine [7].
crystal structure of 4a) an Figure 2 for 4b. The thermal
ellipsoid representation of both conformers A and B for 4a
does not show any significant deformation of the elec-
tronic distribution. The C-C, C-N and C-Cl bond lengths in
the three aromatic rings are close to 1.40(1), 1.32(1) and
1.73(1) Å for 4a and 1.377(4), 1.331(4), 1.734(3) Å for 4b.
The three aromatic rings (atoms C1 to C6), (atoms C9 to
C14) and (atoms C15, C16, N17, C18, N19 and C20) are
found roughly planar for 4a and perfectly planar for 4b
with chlorine atoms slightly out of the mean planes.
The molecular conformations of the positional isomers
4a and 4b are perfectly described by the torsion angles
around the C4-C7, C7-C8, C8-C9 and C7-C15 bonds (see
Table 2). The crystalline conformations are only very
weakly perturbed by their molecular environment and
should be very close to that found in the liquid phase
In conclusion, we synthesized two new pyrimidine
derivatives, 5-[1-(2,3-dichlorophenyl)-2-phenylethyl]-
2,4,6-trichloropyrimidine (4a) and 5-[1-(2,4-
dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine
(4b), according to a method used for preparing the 5-[1-(4-
chlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimidine.
These compounds were well characterized by spectro-
scopic analysis and X-ray structure determination.
Moreover, the analytical results allowed the structural
comparison since these compounds differ by the chlorine
atoms on a phenyl ring. It appears that this difference
improves the antibacterial properties with the new pyrimi-
dine derivatives 4a and 4b. These preliminary satisfactory
results should encourage the continued development this
series of trichloropyrimidines.

54
H. Allouchi, Y. Fellahi, C. Hébert, C. Courseille and Y. Frangin
Vol. 40
EXPERIMENTAL
7.41 (t, 1H, J = 7.8 Hz, ArH), 7.60 (dd, 1H, J = 7.8 Hz, J = 1.6 Hz,
ArH), 7.72 (dd, 1H, J = 7.8 Hz, J = 1.6 Hz, ArH), 8.26 (s, 1H,
ArCH), 11.32 (s, 1H, NH), 11.54 (s, 1H, NH).
2,3-Dichlorobenzaldehyde, 2,4-dichlorobenzaldehyde, barbi-
turic acid, benzyl bromide, zinc, phosphorus oxychloride and
phosphorus pentachloride were purchased from Acros organics.
All reagents were used without purification and all solvents were
5-(2,4-Dichlorobenzylidene)barbituric Acid (1b).
The reaction was performed with 2,4-dichlorobenzaldehyde to
yield compound 1b as a yellow solid, 12.79 g (90 %); ir (potas-
sium bromide) : ν 3200 (NH), 3072, 1760, 1710, 1692 (C=O),
1590, 1577 (aromatic ring), 1438, 1380, 1326, 1260, 1223, 1176,
1
usually redistilled and dried. H nmr spectra were recorded at 200
13
MHz and C nmr spectra were recorded at 50 MHz on a Brüker
Avance DPX 200 instrument. Chemical shifts were measured as
-1
1107, 1050, 945, 838, 791, 757, 670 cm ; uv (ethanol) λmax 204
δ units (ppm) relative to tetramethylsilane. Infrared spectra were
1
nm (ε 12,500), 259 nm (ε 7,300), 326 nm (ε 500); H nmr
-1
recorded from 4000 to 600 cm on a Perkin-Elmer ftir Paragon
(dimethyl-d sulfoxide): δ 7.50 (dd, 1H, J = 8.5 Hz, J = 2 Hz,
6
1000 spectrometer. Samples for ir studies were prepared as fused
potassium bromide disc. Ultraviolet spectra were performed on a
Secomam Anthelie spectrometer using ethanol as solvent. Mass
spectra were obtained on a Hewlett Packard HP 5989A spectrom-
eter. The purity of the synthesized compounds was verified by
gas chromatography (gc, HP 5890A, II) coupled with a mass
spectrometer. A 25 m x 0.2 mm fused silica capillary column
OVI (HP1) Hewlett Packard was directly inserted into the ion
source of the HP quadrupole mass spectrometer through a heated
(250°C) interface box. Helium was used as carrier gas, with a
flow rate through the column of 0.7 ml/min. The temperature
remained at 70°C for 1 min and was then programmed up to 300
°C at 10 °C/min. The final time was 60 min. The temperature of
the ion source was 200 °C and the energy of bombarding elec-
trons was 70 eV. Melting points were determined with a Kofler
hot stage apparatus and are uncorrected. The results of elemental
analyses (C, H, N, Cl) were within ±0.4% of theoretical values.
Microanalyses were carried out at the service central d'analyse
CNRS, Vernaison, France.
ArH), 7.76-7.80 (m, 2H, ArH), 8.23 (s, 1H, ArCH), 11.32 (s, 1H,
NH), 11.53 (s, 1H, NH).
Benzylzinc Bromide (2).
According to a procedure described by Gaudemar [5] benzylz-
inc bromide (2) was obtained by reaction between benzyl bro-
mide (14.36 g, 84 mmol) and zinc (5.5 g, 84 mmol) in dry THF
(40 mL), blanketed under nitrogen gas at 25-30 °C. The organoz-
inc reagent 2 was used in situ for the synthesis of compounds 3a
and 3b.
General Procedure for Preparation of 5-[1-(Dichlorophenyl)-2-
phenylethyl]barbituric Acids (3).
According to a previously described method [1,2], a solution of
the benzylzinc bromide (2) (84 mmol) in THF was cooled at 0 °C
and the 5-benzylidenebarbituric acid (1a) or (1b) (5.46 g, 19
mmol) was added with stirring and cooling. The temperature of
the mixture quickly rose to 30 °C. When it began to fall the cool-
ing bath was removed. After stirring at room temperature for 1 h,
the mixture was hydrolysed with crushed ice (60 g) and concen-
trated hydrochloric acid (10 mL); ether (60 mL) was then added.
The two phases were separated and the aqueous layer was
extracted with ether (3 x 40 mL). The combined organic phase
was washed with brine (100 mL), dried with anhydrous sodium
sulfate and evaporated to give the crude solid product 3. For
purification, the crude product was dissolved in aqueous 0.5 N
sodium hydroxide (240 mL). The aqueous layer was washed with
ether (3 x 40 mL). Strong hydrochloric acid (15 mL) was then
added to precipitate product 3. This product was dissolved in ether
(120 mL), washed with brine (4 x 25 mL) and dried with anhy-
drous sodium sulfate. The solvent was removed under vacuum.
X-ray Structure Determination.
The X-ray diffraction study allows us to obtain the spatial con-
formation of the compounds 4a and 4b. The crystals of these
compounds were obtained by slow evaporation of solution in
ethanol and choloroform mixtures. The crystals are colourless
prisms. Intensity data were collected on an Enraf-Nonius CAD-4
diffractometer equipped using monochromated Cu(kα) radiation
at room temperature (298 K) with an ω-2θ scan. The structure
was solved by direct methods SHELXS-97 [8] and refined with
SHELXL-97 [8]. Scattering factors were taken from International
Tables for Crystallography [9]. The hydrogen atoms were intro-
duced in their theoretical positions and allowed to ride with the
atoms to which they are attached. The crystal data, the data col-
lection conditions and the structure refinement, are given in Table
1. Figures were prepared from PLATON-99 [6].
5-[1-(2,3-Dichlorophenyl)-2-phenylethyl]barbituric Acid (3a).
The reaction of benzylzinc bromide (2) with 5-(2,3-dichloro-
benzylidene)barbituric acid (1a) yielded compound 3a as a color-
less solid, 5.02 g (70 %), mp 105-107 °C; ir (potassium bromide):
ν 3218 (NH), 3092, 2847, 1730, 1715, 1694 (C=O), 1612, 1592,
1582, 1496 (aromatic rings), 1353, 1228, 1180, 1104, 786, 700
General Procedure for Preparation of 5-Benzylidenebarbituric
Acids (1).
They were obtained according to a described method [3] by
condensing the dichlorobenzaldehyde (8.75 g, 50 mmol) with
barbituric acid (6.4 g, 50 mmol) dissolved in hot water (60 mL).
-1
1
cm ; uv (ethanol): λmax 278 nm (ε 4,200); H nmr (deuteri-
ochloroform): δ 3.13 (dd, 1H, J = 14.0 Hz, J = 6.7 Hz, ArCHH),
3.32 (dd, 1H, J = 14.0 Hz, J = 9.8 Hz, ArCHH), 3.62 (d, 1H, J =
3.0 Hz, COCHCO), 4.72 (m, 1H, ArCH), 7.13 - 7.41 (m, 8H,
ArH), 7.97 (s, 1H, NH), 8.17 (s, 1H, NH).
5-(2,3-Dichlorobenzylidene)barbituric Acid (1a).
The reaction was performed with 2,3-dichlorobenzaldehyde to
yield compound 1a as a yellow solid, 12.04 g (85 %), mp 253-
255 °C; ir (potassium bromide): ν 3252 (NH), 3102, 2806, 1770,
1745, 1729, 1714, 1694, 1684 (C=O), 1614, 1571, 1555, 1520,
1500 (aromatic ring), 1428, 1372, 1319, 1272, 1258, 1214, 1185,
5-[1-(2,4-Dichlorophenyl)-2-phenylethyl]barbituric Acid (3b).
The reaction of benzylzinc bromide (2) with 5-(2,4-dichloro-
benzylidene)barbituric acid (1b) yielded compound 3b as a col-
orless solid, 5.77 g (81 %), mp 88-90 °C; ir (potassium bromide):
ν 3218 (NH), 3100, 2860, 1730, 1710, 1694 (C=O), 1590, 1550,
-1
1050, 948, 916, 787, 754, 721 cm ; uv (ethanol) λmax 281 nm (ε
1
3,800), 314 nm (ε 5,500); H nmr (dimethyl-d sulfoxide): δ
6

Jan-Feb 2003
Synthesis and Crystal Structure Characterization of two new Antibacterial Agents
55
-1
5-[1-(2,4-Dichlorophenyl)-2-phenylethyl]-2,4,6-trichloropyrimi-
dine (4b).
1490 (aromatic rings), 1470, 1410, 1360, 1105, 819, 700 cm ; uv
1
(ethanol): λmax 220 nm (ε 28,000), 265 nm (ε 7,200); H nmr
(deuteriochloroform): δ 3.05 (dd, 1H, J = 13.7 Hz, J = 7.4 Hz,
ArCHH), 3.24 (dd, 1H, J = 13.7 Hz, J = 9.6 Hz, ArCHH), 3.54 (d,
1H, J = 2.8 Hz, COCHCO), 4.54 (m, 1H, ArCH), 7.24 (m, 6H,
ArH), 7.31 (d, 1H, J = 2.2 Hz, ArH), 7.37 (d, 1H, J = 8.5 Hz,
ArH), 8.33 (s, 1H, NH), 8.55 (s, 1H, NH).
The reaction with barbituric acid 3b yielded compound 4b
which was crystallized from ethanol-chloroform as colorless
prisms, 2.76 g (64 %), mp 76-78 °C; ir (potassium bromide): ν
3045, 3026, 2908, 2847, 1934, 1852, 1653, 1592, 1582, 1556,
1529, 1496 (aromatic rings), 1469, 1444, 1372, 1329, 1275,
-1
General Procedure for Preparation of 5-[1-(Dichlorophenyl)-2-
1214, 1103, 1050, 1014, 945, 882, 820, 754, 699 cm ; uv
phenylethyl]-2,4,6-trichloropyrimidines (4).
(ethanol): λmax 283nm (ε 3,000), 300 nm (ε 1,700), 311 nm (ε
1,400); H nmr (deuteriochloroform): δ 3.59 (d, 2H, J = 8.2 Hz,
1
According to a previously described method [4], a mixture of
barbituric acid 3 (3.77 g, 10 mmol) and phosphorus oxychloride
(3.06 g, 20 mmol) was heated under reflux (105 °C) overnight.
After cooling to room temperature, phosphorus pentachloride
(6.24 g, 30 mmol) was added. Refluxing was then continued
overnight. After cooling, the reaction mixture was poured onto
ice and allowed to stand 30 min. Product 4 was extracted with
ether (3 x 40 mL), decolorized with charcoal and then filtered.
The organic layer was treated by excess of 2 N sodium hydrox-
yde (20 mL, 40 mmol) and washed with brine until neutral. The
organic phase was then dried with anhydrous sodium sulfate
and the solvent was removed. The residue was purified by
recrystallization.
ArCH ), 5.17 (t, 1H, J = 8.2 Hz, ArCH), 7.10-7.15 (m, 7H, ArH),
7.68 (d, 1H, J = 8.4 Hz, ArH); C nmr (deuteriochloroform): δ
2
13
36.7 (CH ), 44.2 (CH), 127.2 (arom. CH), 127.8 (arom. CH),
2
129.3 (arom. CH), 129.7 (arom. CH), 130.4 (arom. CH), 131.4
(arom. C), 132.4 (arom. CH), 134.7 (arom. C), 135.5 (arom. C),
135.6 (arom. C), 137.3 (arom. C), 157.6 (C-Cl), 163.9 (C-Cl);
+
+
gc/ms: Rt = 33.6 min; ms: m/z 438 [M + 8] (0.1), 436 [M + 6]
+
+
+
(1.4), 434 [M + 4] (3.7), 432 [M + 2] (5.4), 430 M (3.6), 345
35
37
+
35
37
+
[C H N Cl Cl ] (0.8), 343 [C H N Cl Cl ] (2.8),
11
4
2
2
3
11
4
2
3
2
35
37
+
35
+
341 [C H N Cl Cl] (5.0), 339 [C H N Cl ] (3.3), 305
11
4
2
4
11
4
2
5
(3.2), 269 (2.8), 208 (3.6), 178 (1.4), 138 (1.4), 92 (33.6), 91
+
[C H ] (100), 65 (37.8).
7
7
Anal. Calcd. for C H Cl N : C, 49.98;H, 2.56; N, 6.47; Cl,
18 11
5 2
5-[1-(2,3-Dichlorophenyl)-2-phenylethyl]-2,4,6-trichloro-
pyrimidine (4a).
40.98. Found: C, 50.19; H, 2.81; N, 6.60; Cl, 41.29.
The reaction with barbituric acid 3a yielded compound 4a
which was crystallized from ethanol-chloroform as colorless
prisms, 2.24 g (52 %), mp 61-63 °C; ir (potassium bromide): ν
3041, 3029, 2929, 2867, 1929, 1883, 1638, 1592, 1561, 1528,
1496 (aromatic rings), 1458, 1449, 1408, 1328, 1269, 1208, 1158,
REFERENCES AND NOTES
[1] Y. Fellahi, P. Dubois, D. Mandin, J.-E. Ombetta-Goka, J.
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(1995).
[2] Y. Fellahi, P. Dubois, V. Agafonov, F. Moussa, J.-E.
Ombetta-Goka, J. Guenzet and Y. Frangin, Bull. Soc. Chim. Fr., 133,
869 (1996).
[3] J. H. Speer, T. C. Dabovich, W. E. Bachmann and R. O.
Edgerton, in Organic Syntheses Collective, Vol 3, H. Gilman, ed,
John Wiley & Sons, New York, NY, 1955, pp 39-41.
[4] H. Gershon, R. Braun, A. Scala and R. Rodin, J. Med.
Chem., 7, 808 (1964).
[5] M. Gaudemar, Bull. Soc. Chim. Fr., 974 (1962).
[6] A. L. Spek, Platon99, Program for Drawing Crystal and
Molecular Diagrams, Univ. of Utrecht, Netherlands (1999).
[7] Unpublished results.
-1
1077, 1048, 954, 862, 808, 776, 752, 700 cm ; uv (ethanol):
1
λmax 283 nm (ε 2,800), 300 nm (ε 1,400), 311 nm (ε 1,100); H
nmr (deuteriochloroform): δ 3.48 (d, 2H, J = 8.15 Hz, ArCH ),
2
5.10 (t, 1H, J = 8.15 Hz, ArCH), 7.00 (m, 2H, ArH), 7.15 (m, 4H,
ArH), 7.36 (d, 1H, J = 8.0 Hz, ArH), 7.55 (d, 1H, J = 7.8 Hz,
13
ArH); C nmr (deuteriochloroform): δ 35.4 (CH ), 45.2 (CH),
2
127.1 (arom. CH), 128.7 (arom. CH), 128.9 (arom. CH), 132.5
(arom. C), 133.2 (arom. C), 137.4 (arom. C), 137.6 (arom. C),
157.2 (C-Cl), 163.4 (C-Cl); gc/ms: Rt = 35.4 min; ms: m/z 438 [M
+
+
+
+
+ 8] (0.1), 436 [M + 6] (1.4), 434 [M + 4] (4.1), 432 [M + 2]
+
35
37
+
(6.1), 430 M (3.6), 345 [C H N Cl Cl ] (1.1), 343
11
4
2
2
3
35
37
+
35
37
+
[C H N Cl Cl ] (2.8), 341 [C H N Cl Cl] (5.0), 339
11
4
2
3
2
11
4
2
4
35
+
[C H N Cl ] (3.4), 305 (2.1), 269 (3.6), 208 (3.9), 178 (1.7),
[8] G. M. Sheldrick, SHELX97 and SHELXL97 Univ. of
Göttingen, Germany (1997).
11
4
2
5
+
138 (1.4), 92 (44.3), 91 [C H ] (100), 65 (46.4).
7
7
Anal. Calcd. for C H Cl N : C, 49.98; H, 2.56; N, 6.47; Cl,
40.98. Found: C, 50.20; H, 2.63; N, 6.33; Cl, 41.25.
[9] International Tables for X-ray Crystallography, Vol. C,
4.2.6.8-6.1.1.4 (1989).
18 11
5 2