The synthesis of substituted phenylpyrimidines via Suzuki coupling reactions

Article abstract of DOI:10.1002/jhet.5570430119

This paper describes the mon-, di-, and triarylation of the pyrimidine ring. It is possible to introduce one or more aryl rings in generally good yields and in a specific order, namely first in position 4, second in position 6, followed by position 2. A s

Full text of DOI:10.1002/jhet.5570430119

Jan-Feb 2006
127
The Synthesis of Substituted Phenylpyrimidines
via Suzuki Coupling Reactions
Thomas J. Delia, Jennifer M. Schomaker and Alvin S. Kalinda
Malcolm H. Filson Laboratories, Department of Chemistry, Central Michigan University, Mt. Pleasant, MI 48859
Received June 17, 2005
This paper describes the mon-, di-, and triarylation of the pyrimidine ring. It is possible to introduce one
or more aryl rings in generally good yields and in a specific order, namely first in position 4, second in posi-
tion 6, followed by position 2. A study of solvent and catalyst requirements has also been conducted.
J. Heterocyclic Chem., 43, 127 (2006).
Introduction.
function as good nucleophiles gave poor results in the
reaction of (1) with phenylboronic acid (2a) due largely to
the tendency to form ether by-products under the basic
conditions required for the reaction. However use of the
non-nucleophilic t-butyl alcohol solvent gave results com-
parable to those from the glyme/water solvent system.
Polar aprotic solvents such as acetonitrile, acetone, and
tetrahydrofuran, as well as the halogenated polar solvents
chloroform and methylene chloride, all performed well in
the reactions, although the latter two solvents have their
own toxicity issues associated with them. Non-polar sol-
vents such as hexane (slow reaction), toluene, or benzene
gave more by-product formation and increased amounts of
the 2-substituted isomer. Higher boiling aprotic solvents
such as dimethylformamide and dimethylsulfoxide were
also not effective.
The direct arylation of the pyrimidine ring has been the
subject of a limited number of approaches [1-4]. One of
the more interesting arylation applications using Suzuki
coupling involves resin-supported chloropyrimidines [5].
We recently described a convenient arylation of 2,4,6-
trichloropyrimidine (1), using phenylboronic acid (2a)
under Suzuki coupling conditions [6]. In this report the
sequential displacement of the chlorines in very good
yields was achieved. The selectivity for substitution was
also very good following the pattern of position 4 > posi-
tion 6 > position 2, suggesting that controlled multiple sub-
stitutions would be practical.
In this paper we report on our further investigations into
the scope of this reaction, with emphasis on solvent, cata-
lyst, and a variety of substituted phenylboronic acids.
Much work has recently been devoted to exploring
improvements in solvent systems and modified catalysts
[7,8].
Catalyst.
In the initial study catalytic amounts of palladium II
acetate and triphenylphosphine were adopted as the standard
methodology. In an effort to ascertain the optimum parame-
ters we explored several alternatives. Palladium acetate
alone functioned as an effective catalyst initially, but
appeared to gradually decompose to palladium black over
time as evidenced by a darkening of the reaction mixture
and the appearance of fine black particles. This behavior
was not observed when triphenylphosphine was used as the
ligand. Palladium-on-carbon (10%) slowly catalyzed the
Suzuki coupling but also led to reductive dehalogenation.
Palladium acetate with 1,1'-bis(diphenylphosphino)-
Results and Discussion.
Solvent.
In the previous report we identified a glyme/water
medium as a suitable solvent system in order to obtain
good yields of mono-, di-, and triphenyl-substituted pyrim-
idines [6]. Since glyme is a solvent that is prone to perox-
ide formation as well as being a suspected teratogen [9],
we wished to explore other solvent systems. Polar protic
solvents, such as methanol and ethanol, whose anions can

128
T. J. Delia, J. M. Schomaker and A. S. Kalinda
Vol. 43
Table
Product
ferrocene (dppf) or 1,3-bis(diphenylphosphino)propane
(dppp) as ligands gave slower rates of reaction when the
reaction was conducted at room temperature, but rates simi-
lar to those of palladium II acetate/triphenylphosphine when
heated to reflux temperature. Consequently, we conclude
that the initial choice of catalyst provides the best result.
Having established the nature of the catalyst for our fur-
ther studies, we examined the quantity of catalyst required
for optimum yields. Initially we used 2.5-5.0 mol % of pal-
ladium II acetate and twice this amount of triphenylphos-
phine. The palladium II acetate could be reduced to 0.5
mol % and still have reaction completion within 12 h.
The utilization of a variety of starting materials to pro-
duce mono-, di-, and trisubstituted arylpyrimidines is out-
lined in Scheme 1.
Entry
Reactants
% Yield
1
2
3
4
5
6
7
8
2a + 1
2b + 1
2c + 1
2f + 1
2a + 1
2b + 1
2c + 3b
2g + 3b
2g + 3a
2h + 1
2a + 4c
2b + 1 + 2a
2a + 1 + 2b
2b + 1
3a
3b
3c
3f
4a
4b
4c
4d
4e
4f
84[6]
94
82
48
88[6]
88
48
38
54
32
9
10
11
12
13
14
5b
5c
5d
5e
75
83
83
Quant.
Disubstitution.
In our previous report [6] disubstitution leading to (4a)
using phenylboronic acid (2a) was accomplished in 88 %
yield (Entry 5). The results described above for monosubsti-
tution suggested that the order of various substituted phenyl-
boronic acids might be important in order to achieve good
results. First, however, two equivalents of 4-ethylphenyl-
boronic acid (2b) were used to confirm the 4,6-disubstitution
pattern observed previously [6]. Thus, (4b) was prepared in
88 % yield (Entry 6). To determine unequivocally the order
of substitution (3b) was prepared as previously mentioned
and then treated with one equivalent of 4-chlorophenyl-
boronic acid (2c). Compound (4c) was obtained in 48 %
yield using this addition sequence (Entry 7).
Similarly, (3b) was converted into (4d) by using 2g as the
second reagent. The yield was somewhat poorer, though
(38%) (Entry 8). Some improvement was realized when
(3a) was treated with (2g) to give (4e) in 54 % yield (Entry
9). Finally, we wished to explore the utility of more polar
groups in these reactions. Thus (1) was allowed to react with
two equivalents of (2h) which provided the disubstituted
derivative (4f) (Entry 10). This use of two equivalents of (2)
in the same flask in the preparation of both (4b) and (4f)
suggested that sequential formation of trisubstituted pyrim-
idines could be accomplished without isolation of interme-
diates. See below for an example of this methodology.
Monosubstitution.
Monosubstitution of (1) using phenylboronic acid
(2a) previously afforded the 4-substituted pyrimidine
(3a) in high yield [6] (Entry 1, Table 1). By using a
short series of substituted phenylboronic acids we were
able to ascertain the influence substituents had on the
efficiency of the reaction. Both the ethyl- (2b) and
chloro- (2c) phenylboronic acids gave good yields of
the monosubstituted products (3b) and (3c) (Entries 2
and 3). However neither the iodo- (2d) nor formyl (2e)
reagents led to any significant yields of (3d) or (3e),
respectively. In the case of the iodo compound it is
likely that this halogen participated in a self-coupling
reaction rather than the cross-coupling reaction with the
chlorine in (1.) However when the formyl group was
protected with ethylene glycol (2f) a 48 % yield of (3f)
was obtained (Entry 4, Table 1).
Trisubstitution.
Based on the high degree of success with both monosub-
stitution and disubstitution, we felt confident that we could
introduce substituted phenyl rings in any order. Our first
efforts in preparing triphenyl-substituted pyrimidines (5)
began with the corresponding disubstitutedpyrimidine (4).
Thus, (4c) was treated under the usual conditions with
phenylboronic acid (2a). In this manner (5b) was obtained
in 75 % yield (Entry 11). Additional triphenylsubstituted-
pyrimidines (5c, 5d) (Entries 12, 13) were obtained using

Jan-Feb 2006
The Synthesis of Substituted Phenylpyrimidines via Suzuki Coupling Reactions
129
Anal. Calcd. for C H N Cl : C, 46.28; H, 1.94; N, 10.79.
Found: C, 46.01; H, 2.05; N, 10.73.
the one pot methodology by choosing the appropriate
order of addition of various examples of (2). The prepara-
tion of (5c) illustrates this approach quite well.
10
5
2
3
2,4-Dichloro-6-(4'-(1,3-dioxyanyl)phenyl)pyrimidine (3f).
This compound was obtained as a white solid (48 %), mp 132
The reaction flask was initially charged with (1), glyme,
aqueous sodium carbonate, a phenylboronic acid (2b), 2.5
mol % palladium II acetate and 5.0 mol % triphenylphos-
phine. When it was determined (by tlc) that all of the
phenylboronic acid had reacted, a different 4-substituted
phenylboronic acid (2a) was added along with additional
base, but no additional catalyst. Again, upon completion of
this reaction a final charge of this reaction sequence was
one equivalent of 2a. This resulted in an 83 % yield of
(5c). (See Table 1) The formation of (5d) was accom-
plished in a similar manner, though with one less step due
to the use of two equivalents of (2a) in the first step.
Subsequent reaction, without workup, with (2a) gave (5d)
in 83 % yield. Finally (5e) was prepared from (1) using
three equivalents of (2b), in quantitative yield (Entry 14).
1
– 4°; H nmr (deuteriochloroform): δ 1.47-1.59 (t of d, J = 2.0
Hz, 1H), 2.18-2.35 (m, J = 2.0 Hz, 1H), 3.99-4.08 (t of d, J = 4.0
Hz, 2H), 4.29-4.37 (m, J = 6.0 Hz, 2H), 5.58 (s, 1H), 7.64-7.71 (s
13
and d, J = 4.0 Hz, 3H), 8.10 (d, J = 4.0 Hz, 2H); C nmr (deu-
teriochloroform): δ 25.7, 67.5, 100.6, 115.4, 126.9, 127.7, 134.2,
142.9, 160.9, 162.9, 167.7; MS m/z 311 (M+, 26) 251 (M-60,
99).
Anal. Calcd. for C H N Cl : C, 54.04; H, 3.89; N, 9.00.
14 12
2
2
Found: C, 53.81; H, 4.01; N, 8.78.
2-Chloro-4,6-bis-(4'-ethylphenyl)pyrimidine (4b).
To a solution of (1) (0.50 g, 2.7 mmol) in glyme was added 4-
ethylphenylboronic acid (2b) (5.9 mmol), aqueous sodium car-
bonate (16.7 mmol), palladium II acetate (2.5 mol %), and triph-
enylphosphine (5 mol %). The reaction was stirred at 70° for 24
h. The glyme was removed under reduced pressure and the
residue partitioned between dichloromethane and water. After
completion of the work up the residue was purified by column
chromatography to yield (4b) (88 %) as a white solid (hexanes),
EXPERIMENTAL
1
mp 59-63°; H nmr (deuteriochloroform): δ 1.29 (t, J = 3.0 Hz,
1
13
H and C Nmr spectra were obtained using a Varian Inova
(500 MHz) spectrometer. Deuteriochloroform and dimethylsul-
3H), 2.73 (q, J = 4.0 Hz, 2H), 7.37 (d, J = 3.0 Hz, 4H), 7.92 (s,
13
1H), 8.06 (d, J = 5.0 Hz, 4H); C nmr (deuteriochloroform): δ
foxide-d with tetramethylsilane as the internal standard were the
6
15.3, 28.8, 110.1, 127.8, 128.5, 133.0, 148.3, 161.9, 167.3; ms:
m/z 322 (M+, 100).
solvents of choice. A hexane/ethyl acetate solvent mixture was
used to monitor the reaction by tlc. A Hewlett Packard Model
5995A GC/MS instrument was used to obtain all of the molecular
weight information. Both GC and direct insertion probes (DIP)
were used. A dry nitrogen environment was used in all reactions
to ensure an inert atmosphere. Galbraith Analytical Laboratories
of Knoxville, TN performed elemental analyses. High resolution
mass spectra were obtained through the Michigan State
University facilities. Sigma-Aldrich and Acros chemicals were
utilized without further purification.
Anal. Calcd. for C
H N Cl: C, 74.41; H, 5.93; N, 8.68.
20 19 2
Found: C, 74.39; H, 6.09; N, 8.68.
2-Chloro-4-(4'chlorophenyl)-6-(4'-ethylphenyl)pyrimidine (4c).
A mixture of palladium II acetate (0.060 g, 0.245 mmol), triph-
enylphosphine (0.128 g, 0.490 mmol), and glyme (50 mL) was
allowed to stir under a nitrogen atmosphere for 10 min (turns red
in color). To this mixture was added (2c) (0.768 g, 4.91 mmol)
dropwise and allowed to stir for an additional 10 min upon com-
pletion of the addition at which time 3b (1.13 g; 4.46 mmol) dis-
solved in glyme (90 mL) was added to the reaction mixture all at
once and stirred a further 10 min. Sodium carbonate (1.61 g, 15.2
mmol) in water (20 mL) was added to the reaction flask and the
whole heated to 70° for 27 h. The glyme was removed under
reduced pressure and the residue taken up in ethyl acetate (150
mL). The organic solution was washed with water (5 x 100 mL),
dried over anhydrous sodium sulfate, and purified by column
chromatography. The resulting yellow solid was recrystallized
twice from absolute ethanol to give pure (4c) (0.71 g, 48 %), mp
2,4-Dichloro-6-(4'-ethylphenyl)pyrimidine (3b).
To a solution of (1) (0.25 g, 1.36 mmol) in glyme was added 4-
ethylphenylboronic acid (2b) (0.22 g, 1.47 mmol), aqueous
sodium carbonate (4.22 mmol), palladium II acetate (2.5 mol %),
and triphenylphosphine (5 mol %). The reaction was stirred at
70° for 24 h. The glyme was removed under reduced pressure and
the residue partitioned between dichloromethane and water. After
completion of the work up the residue was purified by column
chromatography to yield 3b in 94 % yield as a white solid (hexa-
1
nes), mp 65.0-66.5°; H nmr (deuteriochloroform): δ 1.29 (t, J =
1
77-9 °; H nmr (deuteriochloroform): δ 1.29 (t, J = 4.0 Hz, 3H),
2.5 Hz, 3H), 2.77 (q, J = 2.5 Hz, 2H), 7.36 (d, J = 3.0 Hz, 2H),
13
2.75 (q, J = 3.0 Hz, 2H), 7.35 (q, J = 3.0 Hz, 2H), 7.48-7.57 (m, J
= 3.0 Hz, 3H), 7.93 (s, 1H), 8.07 (t, J = 4.0 Hz, 2H), 8.18 (t, J =
7.60 (s, 1H), 8.00 (d, J = 3.0 Hz, 2H); C nmr (deuteriochloro-
form): δ 15.1, 28.8, 114.7, 127.5, 129.3, 131.3, 149.5, 160.7,
162.6, 168.0; ms: m/z 253 (M+, 41) 252 (M-1, 100).
13
4.0 Hz, 2H); C nmr (deuteriochloroform): δ 15.4, 28.8, 110.2,
127.4, 128.0, 129.7, 132.8, 134.5, 136.8, 137.8, 147.7, 148.7,
162.0, 164.9, 167.8; ms: m/z 329 (M+, 72), 328 (M-1, 100).
Anal. Calcd. for C H N Cl : C, 56.94; H, 3.98; N, 11.07.
12 10
2
2
Found: C, 57.13; H, 4.06; N, 10.99.
Hrms (EI): m/z calcd. for C H Cl N = 328.0534; found: m/z
= 328.0533.
18 14
2 2
2,4-Dichloro-6-(4'-chlorophenyl)pyrimidine (3c).
This compound was obtained as a white solid (82 %), mp 127
2-Chloro-4-(4'-ethylphenyl)-6-(4'fluorophenyl)pyrimidine (4d).
1
– 9°; H nmr (deuteriochloroform): δ 7.49 (d, J = 1.5 Hz, 2H),
13
7.65 (s, 1H), 8.09 (d, J = 1.4 Hz, 2H); C nmr (deuteriochloro-
This compound was prepared in a manner analogous to that for
form): δ 115.1, 128.8, 129.5, 132.5, 138.9, 161.0, 163.1, 166.8;
ms: m/z 259 (M+, 100).
(4c), from (3b) and (2g). Colorless crystals of (4d) (38 %), mp
111-3° were obtained; H nmr (deuteriochloroform): δ 1.29 (t, J =
1

130
T. J. Delia, J. M. Schomaker and A. S. Kalinda
Vol. 43
1.6 Hz, 3H), 2.74 (q, J = 1.6 Hz, 2H), 7.21 (t, J = 2.5 Hz, 2H),
7.35 (d, J = 1.7 Hz, 2H), 7.92 (s, 1H), 8.05 (d, J = 1.4 Hz, 2H),
8.13-8.16 (dd, J = 1.0 Hz, 2H); C nmr (deuteriochloroform): δ
15.3, 28.8, 110.1, 116.1, 116.2, 127.4, 128.6, 129.5, 129.6, 131.9,
132.9, 148.6, 161.9, 163.9, 166.2, 167.6; ms: m/z 312 (M+, 100),
acetate (2.5 mol %), and triphenylphosphine (5 mol %). The reac-
tion mixture was stirred at 70° for 24 h. A solution of (2b) (2.7
mmol) in glyme and an additional quantity of aqueous sodium
carbonate (8.4 mmol) was added and the reaction mixture heated
for a further 24 h. Finally, another portion of (2a) (2.7 mmol) in
glyme and aqueous sodium carbonate (8.4 mmol) was added and
heating continued for 24 h. After workup the product was puri-
fied by column chromatography to afford 5c as a white solid (83
13
297 (M-15, 57). Hrms (EI): m/z calcd. for C
312.0830; found: m/z = 312.0822.
H
ClFN
=
18 14
2
2-Chloro-4-(4'-fluorophenyl)-6-phenylpyrimidine (4e).
1
%), mp 85.0-6.5°; H nmr (deuteriochloroform): δ 1.39 (t, J = 4.0
This compound was prepared in a manner analogous to that for
Hz, 3H), 2.31 (q, J = 4.0 Hz, 2H), 7.43 (d, J = 3.0 Hz, 2H), 7.58-
7.69 (overlapping signals, J = 4.0 Hz, 6H), 7.98 (s, 1H), 8.31 (d, J
(4c), from (3a) and (2g) using tetrahydrofuran as solvent.
1
13
Colorless crystals of (4e) (54 %), mp 114-7° were obtained; H
= 8.0 Hz, 4H), 8.80 (d, J = 7.0 Hz, 2H); C nmr (deuteriochloro-
nmr (deuteriochloroform): δ 7.20 (t, J = 4.0 Hz, 2H), 7.53 (t, J =
form): δ 15.3, 28.6, 109.6, 127.0, 127.1, 128.1, 128.2, 128.4,
128.7, 130.3, 130.4, 134.7, 137.3, 138.1, 147.1, 164.0, 164.1,
13
5.0 Hz, 3H), 7.94 (s, 1H), 8.14-8.18 (m, J = 5.0 Hz, 6H); C nmr
(deuteriochloroform): δ 110.1, 116.2, 127.4, 128.6, 129.5, 131.8,
132.9, 148.6, 161.9, 163.9, 166.2, 167.6; ms: m/z 284 (M+, 100),
164.3; ms: m/z 336 (M+, 100). Anal. calcd. for C H N : C,
85.68; H, 5.99; N, 8.33. Found: C, 85.76; H, 6.21; N, 8.28.
24 20
2
249 (M-35, 85). Hrms (EI): m/z calcd. for C
284.0517;found: m/z = 284.0519
H ClFN =
16 10 2
4,6-Diphenyl-2-(4'-ethylphenyl)pyrimidine (5d).
To a solution of (1) (2.7 mmol) in glyme was added (2a) (5.4
mmol), aqueous sodium bicarbonate (8.4 mmol), palladium II
acetate (2.5 mol %), and triphenylphosphine (5 mol %). The reac-
tion mixture was stirred at 70° for 24 h. A solution of (2b) (2.7
mmol) in glyme and an additional quantity of aqueous sodium
carbonate (8.4 mmol) was added and the reaction mixture heated
for a further 24 h. After workup the product was purified by col-
umn chromatography to afford (5d) as a white solid (83 %), mp
2-Chloro-4,6-bis-(3'-aminophenyl)pyrimidine (4f).
This compound was prepared using the method for (4b) except
that 2,2-dimethoxypropane was the solvent. The crude product
was recrystallized from absolute ethanol to give deep yellow
1
crystals (32 %), no mp below 250°; H nmr (dimethylsulfoxide-
d ): δ 1.58 (s, 1H), 3.85 (s, 3H), 6.86 (s, 2H), 7.26-7.32 (m, J =
6
1
2.5 Hz, 2H), 7.44 (d, J = 2.6 Hz, 2H), 7.50 (d, J = 1.0 Hz, 2H),
95-98°; H nmr (deuteriochloroform): δ 1.42 (t, J = 2.0 Hz, 3H),
13
7.92 (s, 1H); C nmr (dimethylsulfoxide-d ): δ 113.6, 117.4,
2.89 (q, J = 3.0 Hz, 2H), 7.53 (d, J = 3.0 Hz, 2H), 7.59-7.70 (over-
lapping signals, J = 2.0 Hz, 6H), 7.96 (s, 1H), 8.45 (d, J = 4.0 Hz,
6
118.1, 129.8, 136.6, 147.1, 161.7, 170.6; ms: m/z 296 (M+, 100).
Hrms (EI): m/z calcd. for C H ClN = 296.0829; found: m/z =
13
4H), 8.85 (d, J = 3.0 Hz, 2H); C nmr (deuteriochloroform): δ
16 13
4
296.0827.
15.7, 29.1, 110.0, 127.4, 128.1, 125.8, 128.9, 130.8, 136.0, 137.6,
147.2, 164.5; MS m/z 336 (M+, 100).
4-(4'-Chlorophenyl)-6-(4'-ethylphenyl)-2-phenylpyrimidine
(5b).
Anal. Calcd. for C H N : C, 85.68; H, 5.99; N, 8.33. Found:
24 20
2
C, 85.64; H, 5.95; N, 8.43.
A mixture of palladium II acetate (0.023 g, 0.103 mmol), triph-
enylphosphine (0.054 g, 0.205 mmol), and tetrahydrofuran (50
mL) was allowed to stir under a nitrogen atmosphere for 10 min
(turns red in color). To this mixture was added (2a) (0.25 g, 0.205
mmol) in tetrahydrofuran (90 mL) dropwise and allowed to stir
for an additional 10 min upon completion of the addition. (4c)
(0.675 g, 0.205 mmol) dissolved in tetrahydrofuran (50 mL) was
added to the reaction mixture all at once and stirred a further 10
min. Sodium carbonate (0.652 g, 6.15 mmol) in water (20 mL)
was added to the reaction flask and the whole heated to reflux for
27 h. The solvent was removed under reduced pressure and the
residue taken up in ethyl acetate (150 mL). The organic solution
was washed with water (5 x 100 mL), dried over anhydrous
sodium sulfate, and purified by column chromatography. The
resulting yellow solid was recrystallized from absolute ethanol to
2,4,6-Tris-(4'-Ethylphenyl)pyrimidine (5e).
To a solution of (1) (1.4 mmol) in glyme was added (2b) (4.3
mmol), aqueous sodium carbonate (13.0 mmol), palladium II
acetate (2.5 mol %), and triphenylphosphine (5 mol %). The reac-
tion was stirred at 70° for 24 h. Following workup the residue
was purified by column chromatography to give (5e) as a white
1
solid (quant. yield), mp ~ rt; H nmr (deuteriochloroform): δ
1.38-1.48 (2 overlapping t, J = 3.0 Hz, 9H), 2.80-2.94 (2 overlap-
ping q, J = 5.0 Hz, 6H), 7.51 (2 d in a ratio of 2:1, J = 3.0 Hz, 6H),
8.00 (s, 1H), 8.33 (d, J = 4.0 Hz, 4H), 8.83 (d, J = 3.0 Hz, 2H);
13
C nmr (deuteriochloroform): δ 15.6, 15.7, 28.9, 29.0, 109.4,
127.3, 128.0, 128.4, 128.6, 135.2, 136.1, 147.0, 147.2, 164.4,
164.5; MS m/z 356 (M+, 100).
Anal. Calcd. for C H N : C, 85.67; H, 7.19; N, 7.14. Found:
25 28
2
1
give pure (5b) as a white solid (0.057 g, 75 %), mp 115-7 °; H
C, 85.28; H, 7.39; N, 7.11.
nmr (deuteriochloroform): δ 1.28 (t, J = 3.0 Hz, 3H), 2.72 (q, J =
2.7 Hz, 2H), 7.41 (d, J = 5.0 Hz, 2H), 7.49-7.55 (m, J = 9.0 Hz,
5H), 7.86 (s, 1H), 8.20-8.24 (m, J = 5.0 Hz, 4H), 8.73 (d, J = 3.0
Acknowledgements.
13
We thank Dennis P. Anderson for his assistance with nmr data
and Gary Tang and Chris Crouse for their efforts at providing low
resolution mass spectral data. Our most sincere appreciation is
extended to Bev Chamberlin, of the MSU Mass Spectrometry
Facility for providing the hrms for some of the compounds.
Finally we acknowledge, with gratitude, the financial assis-
tance provided by the Community Cancer Services of Mt.
Pleasant.
Hz, 1H); C nmr (deuteriochloroform): δ 15.3, 28.8, 110.1,
116.0, 116.2, 127.4, 128.6, 129.5, 129.6, 131.8, 123.9, 148.6,
162.0, 163.9, 166.2, 167.6; ms: m/z 370 (M+, 100). Hrms (EI):
m/z calcd. for C H ClN = 370.1237; found: m/z = 370.1236.
24 19
2
2,4-Diphenyl-6-(4'-ethylphenyl)pyrimidine (5c).
To a solution of (1) (2.7 mmol) in glyme was added (2a) (2.7
mmol), aqueous sodium bicarbonate (8.4 mmol), palladium II

Jan-Feb 2006
The Synthesis of Substituted Phenylpyrimidines via Suzuki Coupling Reactions
131
REFERENCES AND NOTES
[5] J. V. Wade and C. A. Krueger, J. Comb. Chem., 5, 267
(2003).
[6] J. M. Schomaker, and T. J. Delia, J. Org. Chem., 66, 1725
(2001).
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