Aryl-aryl bonds formation in pyridine and diazine series. Diazines part 41

Article abstract of DOI:10.1002/jhet.5570420726

The synthesis of several symmetrical polyaromatic compounds with pyridine or diazine units has been achieved by homocoupling of aryl halides with Pd(OAc)₂ as catalyst. Cross-coupling reactions of aryl Grignard reagents with Fe(acac)₃ as catalyst allowed the synthesis of various unsymmetrical polyaryl- or polyheteroaryl compounds with π-deficient rings.

Full text of DOI:10.1002/jhet.5570420726

Nov-Dec 2005
1423
Aryl-Aryl Bonds Formation in Pyridine and Diazine Series.
Diazines Part 41
a
b
a
a
Ludovic Boully, Mircea Darabantu, Alain Turck, Nelly Plé*
a) Laboratoire de Chimie Organique Fine et Hétérocyclique, UMR 6014
IRCOF-INSA, B.P. 08, 76131 Mont St Aignan Cedex (France).
b) Department of Organic Chemistry ,"Babes-Bolyai" University
11 Aranyi Janos Str., 400028 Cluj-Napoca (Romania).
nelly.ple@insa-rouen.fr.; Tel +33-2-35-52-29-02; Fax +33-2-35-52-29-62
Received March 29, 2005
The synthesis of several symmetrical polyaromatic compounds with pyridine or diazine units has been
achieved by homocoupling of aryl halides with Pd(OAc) as catalyst. Cross-coupling reactions of aryl
2
Grignard reagents with Fe(acac) as catalyst allowed the synthesis of various unsymmetrical polyaryl- or
3
polyheteroaryl compounds with π-deficient rings.
J. Heterocyclic Chem., 42, 1423 (2005).
Aryl-aryl bond formation is one of the most important
triaromatic rings are the backbone of some of the most
efficient ligands used as asymmetric catalysts especially
when atropoisomery is possible [5], or as complexes with
heavy metals [6].
Among the various efficient methods for the construction
of carbon-carbon bonds, the transition metal-catalyzed cross-
coupling reactions have become an attractive procedure.
Biaryls are usually prepared from aryl iodides, bromides or
triflates, either by Ullmann coupling [7] or by Palladium-,
tools of modern organic synthesis. These bonds are very
often found in natural products [1] such as alkaloids as
well as in numerous biologically active parts of pharma-
ceutical and agrochemical specialities including pyridine
or/and diazine moieties. Polyaromatics also possess origi-
nal physical properties which could lead to various appli-
cations such as organic conductors [2], optoelectronic
devices [3] and liquid crystals [4]. Last but not least, di- or
Table 1
Homocoupling Reactions of Chlorodiazine
Scheme 1
Entry
1
Substrate 1
Product 2
Compound [Ref.] [a]
Yield
2a
97%
[14]
2
3
2b
[15]
95%
76%
2c
[16]
4
5
2d
[17]
96%
39%
2e
[18]
[a] All products 2 have been characterized and comparison with already published data are in agreement.

1424
L. Boully, M. Darabantu, A. Turck, N. Plé
Vol. 42
Nickel- or Iron cross-coupling reactions of arylboranes [8],
organotins [9] and aryl Grignard reagents [10].
tetrabutylammonium bromide mixture (Pd(OAc) /(n-
2
Bu NBr) as a catalyst to induce homocoupling of various
4
Using these methodologies, we report here syntheses of
symmetrical and unsymmetrical di-and poly-arylcom-
pounds with one or several π-deficient heterocycles such
as pyridine or diazine.
chlorodiazines (Table 1, Scheme 1). Using this catalyst,
dimers 2a-2d are obtained in good yields with chlorodi-
azines (entries 1-4), whereas a lower yield was observed
with the 2-phenyl-4-chloroquinazoline (entry 5).
Among the synthetic known procedures for the con-
struction of unsymmetrical biaryls with a π-deficient
heterocycle, cross-coupling reactions between aryl
Grignard reagents and heteroaryl halides provide an
efficient method. Such cross-coupling, reactions cat-
alyzed with palladium or nickel. have been reported in
the literature [12b,19]. Recently, iron complexes such
The most usual way to prepare symmetrical biaryls is the
Ullmann [11] synthesis which consists of the condensation
of two molecules of aryl halides in the presence of copper,
generally at a high temperature. More recently, other meth-
ods have been developed based on either a Ni(0)Zn [12]
coupling or a Pd/formiate [13,14] coupling and have been
reported to synthesize bipyridines.
as Iron III acetylacetonate Fe(acac) seemed to be effi-
The association of palladium acetate Pd(OAc) and
3
2
Scheme
2
Table 2
Cross-coupling Reactions of Phenylmagnesium Bromide with Heteroaryl Chlorides (Het-Cl)
Scheme
3
Entry
1
Het-Cl
Product
Compound
[Ref]
Yield
Isolated
Entry
4
Het-Cl
Product
Compound
[Ref]
Yield
Isolated
9 [23]
39%
6
68%
2
3
7 [21]
50%
38%
5
10 [24]
33%
8
[22]
cient catalysts to achieve cross-coupling reactions of
alkyl or aryl Grignard reagents with aryl or heteroaryl
chlorides [20]. Using this last methodology, we
tetra-n-butylammonium bromide (n-Bu NBr) has been
used as a convenient catalytic alternative for Ullmann type
reactions [14]. We investigated the palladium diacetate/
4

Nov-Dec 2005
Aryl-Aryl Bonds Formation in Pyridine and Diazine Series. Diazines Part 41
1425
describe here the synthesis of different polyaryl- or
polyheteroaryl compounds.
chloride allowed cross-coupling reaction leading to com-
pounds 11-18 (Scheme 4, Table 3).
First, we have tested the reaction of chloropyrazine
with several arylmagnesium bromides leading to the
substituted phenylpyrazine derivatives 3-5 in good
yields. Nevertheless, the reaction failed with mesityl-
magnesium bromide, probably due to steric hindrance
(Scheme 2).
Reaction of the π-deficient heteroarl halides with
phenylmagnesium bromide under similar experimental
conditions gave compounds 6-10 in moderate yields
(Scheme 3, Table 2).
In terms of yields, the results compiled in Table 3 are
comparable or slightly lower than those obtained in related
Palladium- or Nickel catalyzed cross-coupling reactions of
aryl Grignard reagents with π-deficient heterocycles previ-
ously described in the literature. The high reaction rates at
low temperature using Fe(acac) , a catalyst of low cost,
3
makes this method attractive to access to a wide range of
unsymmetrical polyaza heterocyclic compounds.
Conclusion.
Using Pd(OAc) as catalyst, we have developed the
2
In search for new polyaza heterocyclic compounds, we
have extended these cross-coupling processes to the reac-
tion of several π-electron-deficient heteroaryl chlorides
with pyridylmagnesium chlorides under the above exper-
imental conditions. Reactions with 2- and 4-pyridylmag-
nesium chlorides failed whereas 3-pyridylmagnesium
syntheses of various symmetrical dimers of π-deficient
heterocyclic compounds. Reactions of aryl Grignard
reagents catalyzed with Fe(acac) provide a promising
3
method to synthesize building blocks, with pyridine and
diazine units, which already have a growing interest in
supramolecular chemistry and material science. Further
Table 3
Cross-coupling Reactions of 3-Pyridylmagnesium Chloride with Heteroaryl Chlorides (Het–Cl)
Scheme 4
Entry
1
Het-Cl
Product
Compounds
[Ref]
Yield
Isolated
Entry
6
Het-Cl
Product
Compounds
[Ref]
Yield
Isolated
11
[19c, 25]
47%
16
21%
[29]
2
3
4
12
[19c, 26]
39%
32%
22%
7
17
43%
[30]
13
14
[27]
5
15
40%
[28]

1426
L. Boully, M. Darabantu, A. Turck, N. Plé
Vol. 42
teriochloroform): δ 3.81 (s, 3H), 6.95 (d, J = 8.3 Hz, 1H), 7.05 (t,
work along those lines is currently in progress in our
laboratory.
J = 7.55 Hz, 1H), 7.35 (t, J = 7.55 Hz, 1H), 7.73 (d, J = 7.55 Hz,
13
1H) , 8.38 (s, 1H), 8.57 (s, 1H), 9.07 (s, 1H); C nmr δ 56.0,
111.7, 121.7, 126.1, 131.5, 131.6, 142.5, 144.5, 146.9, 152.3,
EXPERIMENTAL
+
157.4; ms(EI): m/z 186 (M , 100).
Anal. Calcd. for C H N O (186.21): C, 70.95; H, 5.41, N,
11 10
2
Melting points were determined on a Kofler hot-stage appara-
15.04. Found: C, 70.60; H, 5.79; N, 15.39.
1
13
tus and are not corrected. H, and C nmr spectra were recorded
4-Methoxyphenylpyrazine (5).
1
13
on a Bruker AC 300 (300 MHz H, 75 MHz C) instrument.
Microanalyses were performed on a Carlo Erba CHNOS 1160
apparatus. IR spectra were obtained as potassium bromide pellets
with a Perkin-Elmer Paragon 500 spectrophotometer.
Cross-coupling reaction according the Procedure B with 4-
methoxyphenylmagnesium bromide gave after purification by
column chromatography using n-heptane:dichloromethane (1:1,
v/v) as eluent 291 mg (86%) of 5 as a yellow solid, mp 86-87°;
H NMR (deuteriochloroform): δ 3.85 (s, 3H), 7.00 (d, J = 7.9
Hz, 2H), 7.96 (d, J = 7.9 Hz, 2H), 8.42 (s, 1H), 8.56 (s, 1H), 8.69
For Procedure A, shown below all compounds are known and
were characterized by nmr and microanalyses or GC-MS. Mass
spectra (MS) were recorded on an ATI-Unicam Automass apparatus.
1
+
(s, 1H); ms(EI): m/z 186 (M , 100).
General Procedure A for Palladium Catalyzed Homocoupling
Reaction: Synthesis of Compounds 2a-2e.
Anal. Calcd. for C H N O (186.21): C, 70.95; H, 5.41, N,
11 10
2
15.04. Found: C, 70.71; H, 5.65; N, 15.22.
A mixture of diisopropylamine (1.4 ml, 8.0 mmol), palladium
acetate (0.4 mmol), tetra-n-butylammonium bromide (8.0 mmol),
and a solution of heteroaryl chloride (8.0 mmol) in toluene (1.5
ml) was stirred under nitrogen atmosphere. The mixture was
refluxed and isopropanol (8.0 mmol) was added. The temperature
was maintened at 105 °C for a period of 24 hours. After cooling
at room temperature, water (5.0 ml) and diethylether (50 ml)
were added. The organic phase was separated, washed with water
and dried over magnesium sulfate. The solvent was evaporated
under vacuum. The crude product was purified by column chro-
matography on silica gel.
4-Phenyl-1,1-dimethyl-3-oxo-1,3-dihyrofuro[3,4-c]pyridine (6).
Cross-coupling reaction according the Procedure B with phenyl-
magnesium bromide gave after purification by column chromatog-
raphy using n-heptane/dichloromethane/ethyl acetate (4:5:1, v/v) as
1
eluent 296 mg (68%) of 6 as a yellow solid, mp 149-150°; H nmr
(deuteriochloroform): δ 1.6 (s, 6H), 7.23 (d, J = 4.9 Hz, 1H), 7.41
(d, J = 3.4 Hz, 3H), 7.85 (d, J = 3.4 Hz, 2H), 8.79 (d, J = 4.9 Hz,
13
1H); C nmr δ 27.4, 83.8, 114.7, 118.1, 128.4, 130.4, 130.5, 136.3,
+
153.4, 160.1, 165.4, 167.9; ms (EI): m/z 239 (M , 100).
Anal. Calcd. for C H NO (239.27): C, 75.30; H, 5.48, N,
15 13
2
5.48. Found: C, 75.71; H, 5.51; N, 5.16.
General Procedure B for an Iron-catalyzed Aryl-heteroaryl
Coupling Reaction: Synthesis of Compounds 3-17.
2-Phenylpyrimidine (7) [21].
A mixture of heteroaryl chloride (1.82 mmol), Iron III acetyca-
Cross-coupling reaction according the Procedure B with
phenylmagnesium bromide gave after purification by column
chromatography using eluent n-heptane/dichloromethane/ethyl
acetate (4:5:1, v/v) as eluent 142 mg (50%) of 7 as a yellow solid,
tonate complex Fe(acac) (29 mg, 0.09 mmol) and THF (10 ml)
3
was stirred under a dry nitrogen atmosphere and cooled to –30
°C. A solution of arylmagnesium bromide or 3-pyridylmagne-
sium chloride (4.20 mmol) in THF was added via a syringe. The
resulting mixture was stirred for 10 minutes, then diluted with
diethylether (10 ml) and quenched with brine. The aqueous layer
was extracted with diethylether (3x20 ml). The combined organic
extracts were dried over magnesium sulfate; then the solvent was
evaporated in vacuo. The crude product was purified by column
chromatography on silica gel.
1
mp 75° (lit 73°); H NMR (deuteriochloroform): δ 7.04 (t, J = 4.9
13
Hz, 1H), 7.40 (m, 3H), 8.35 (m, 2H), 8.67 (d, J = 4.9 Hz, 2H);
C
NMR δ 119.0, 128.1, 128.5, 130.7, 137.5, 157.1, 164.7; ms(EI):
+
m/z 156 (M , 100).
Anal. Calcd. for C H N (156.18): C, 76.90; H, 5.16, N,
10
8 2
17.94. Found: C, 76.99; H, 5.12; N, 17.68.
2,3-Diphenylquinoxaline (8) [22].
O-Tolylpyrazine (3).
Cross-coupling reaction according the Procedure B with
phenylmagnesium bromide gave after purification by column
chromatography using eluent n-heptane/isopropanol (98:2, v/v)
as eluent 154 mg (38%) of 8 as a yellow solid, mp 124-125° (lit
Cross-coupling reaction according to the Procedure B with
o-tolylmagnesium bromide gave after purification by column
chromatography using n-heptane/dichloromethane (1:1, v/v) as
1
1
eluent 250 mg (81%) of 3 as a yellow oil; H nmr (deuteriochloro-
124.5°); H nmr (deuteriochloroform): δ 7.44-7.48 (m, 6H), 7.64
form): δ 2.30 (s, 3H), 7.23 (m, 3H), 7.32 (d, J = 7.0 Hz, 1H), 8.40
(dd, J = 7.2, 1.5 Hz, 4H), 7.88 (d, J= 6.4Hz, 2H), 8.31 (d,
13
13
(d, J = 2.4 Hz, 1H), 8.54 (s, 1H), 8.60 (s, 1H); C nmr: δ 20.7,
J=6.4Hz, 2H); C nmr: δ 128.7, 129.2, 129.6, 130.2, 130.4,
+
126.6, 129.6, 130.2, 131.5, 136.7, 137.1, 142.8, 144.2, 145.5,
139.4, 141.6; ms(EI): m/z 282 (M , 100).
+
156.0; ms(EI): m/z 169 (M , 100).
Anal. Calcd. for C H N (282.34): C, 85.08; H, 5.00, N,
20 14
2
Anal. Calcd. for C H N (170.22): C, 77.62; H, 5.92, N,
9.92. Found: C, 85.33; H, 5.40; N, 9.56.
11 10
2
16.46. Found: C, 77.60; H, 5.97; N, 16.39.
4,6-Diphenylpyrimidine (9) [23].
2-Methoxyphenylpyrazine (4).
Cross-coupling reaction according the Procedure B with phenyl-
magnesium bromide gave after purification by column chromatog-
raphy using eluent dichloromethane/ethyl acetate (95:5, v/v) as
eluent 164 mg (39%) of 9 as a yellow solid, mp 100-101° (lit 99.5-
Cross-coupling reaction according to the Procedure B with 2-
methoxyphenylmagnesium bromide gave after purification by
column chromatography using n-heptane/dichloromethane (1:1,
1
1
v/v) as eluent 254 mg (75%) of 4 as a yellow oil; H nmr (deu-
101°); H nmr (deuteriochloroform): δ 7.45 (m, 6H), 7.95 (s, 1H),

Nov-Dec 2005
Aryl-Aryl Bonds Formation in Pyridine and Diazine Series. Diazines Part 41
1427
13
Anal. Calcd. for C H N (234.26): C, 71.78; H, 4.30, N,
23.92. Found: C, 71.64; H, 4.42; N, 23.92.
8.05 (m, 4H), 8.30 (s, 1H); C nmr: δ 113.2, 127.6, 129.1, 131.5,
14 10
4
+
137.4, 159.6, 165.0; ms(EI): m/z 232 (M , 100).
Anal. Calcd. for C H N (232.28): C, 82.73; H, 5.21, N,
12.06. Found: C, 82.76; H, 5.12; N, 12.12.
20 14
2
3-Phenyl-6-(3-pyridyl)pyridazine (15) [28].
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate/isopropanol (90:10, v/v) as
eluent 169 mg (40%) of 15 as a colorless solid, mp 189-190° (litt
2,4-Diphenylpyrimidine (10) [24].
Cross-coupling reaction according the Procedure B with
phenylmagnesium bromide gave after purification by column
chromatography using dichloromethane as eluent 139 mg (39%)
1
190°); H nmr (deuteriochloroform): δ 7.45 (m, 4H), 7.92 (m,
1
2H), 8.10 (m, 2H), 8.49 (d, J = 7.9 Hz, 1H), 8.68 (d, J = 4.9Hz,
of 10 as a yellow solid, mp 64-65 °C (lit 65 °C); H nmr (deuteri-
13
1H), 9.23 (s, 1H); C NMR: δ 90.4, 124.4, 124.6, 124.8, 127.4,
ochloroform): δ 6.70 (dd, 1H), 7.15 (s, 1H), 7.40 (m, 4H), 7.45(d,
13
129.5, 130.8, 134.9, 148.4, 151.3
1H), 8.10 (dd, 2H), 8.50 (dd, 2H), 8.70 (d, 1H); C nmr: δ 114.9,
Anal. Calcd. for C H N (233.27): C, 77.23; H, 4.75, N,
127.6, 128.7, 129.0, 129.4, 131.2, 131.4, 137.3, 138.2, 158.3,
15 11
3
+
18.01 Found: C, 77.20; H, 4.77; N, 18.05.
164.3, 165.0; ms (EI): m/z 232 (M , 100).
Anal. Calcd. for C H N (232.28): C, 82.73; H, 5.21, N,
12.06. Found: C, 82.65; H, 5.35; N, 12.00.
20 14
2
2,3-Di(3-pyridyl)quinoxaline (16) [29].
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate:isopropanol (90:10, v/v) as
eluent 109 mg (21%) of 16 as a colorless solid, mp 200 °C (dec.);
H nmr (deuteriochloroform): δ 7.34 (m, 2H), 7.44 (m, 2H), 8.40
(d, J = 7.9 Hz, 2H), 8.70 (d, J = 4.5 Hz, 2H), 9.01 (s, 2H), 9.30 (d,
J = 1.5 Hz, 2H);
3-Pyridylpyrazine (11) [19c,25].
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate/methanol (90:10, v/v) as elu-
ent 134 mg (47%) of 11 as a yellow solid, mp 93-94° (lit 92-94°);
1
1
H nmr (deuteriochloroform): δ 7.38 (dd, J = 7.9 Hz, 4.5Hz, 1H),
Anal. Calcd. for C H N (284.11): C, 76.O4; H, 4.25, N,
18 12
4
8.27 (dt, J = 7.9 Hz, 1.9 Hz, 1H), 8.51 (d, J = 1.5 Hz, 1H), 8.61 (d,
J =1.5 Hz, 1H), 8.65 (dd, J =4.5 Hz, 1.9 Hz, 1H), 9.00 (s, 1H),
9.18 (d, J = 1.5 Hz, 1H); C nmr: δ 124.2, 132.5, 134.7, 142.4,
144.1, 144.9, 148.5, 150.8, 151.2, ms(EI): m/z 157 (M , 100).
19.71. Found: C, 76.40; H, 4.03; N, 19.57.
13
2-Methlythio-4-(3-pyridyl)pyrimidine (17) [30].
+
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate/isopropanol (90:10, v/v) as
Anal. Calc for C H N (157.17): C, 68.78; H, 4.49, N, 26.74.
9
7 3
Found: C, 68.91; H, 4.32; N, 26.73.
1
eluent 159 mg (43%) of 17 as a yellow solid, mp 94-95°; H
2-(3-Pyridyl)pyrimidine (12) [19c,26].
NMR (deuteriochloroform): δ 2.56 (s, 3H), 7.37 (m, 2H), 8.32 (d,
Cross-coupling reaction according the procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate/isopropanol (90:10, v/v) as
eluent 112 mg (39%) of 12 as a colorless solid, mp 58° (lit 52°);
J = 7.9 Hz, 1H), 8.52 (d, J =5.3 Hz, 1H), 8.65 (d, J = 3.8 Hz, 1H),
13
9.20 (s, 1H); C nmr: δ 14.6, 112.2, 124.1, 132.4, 135.0, 148.8,
+
152.1, 158.3, 161.9, 173.7; ms (EI): m/z 203 (M , 100).
Anal. Calcd. for C H N S (203.26): C, 59.09; H, 4.46, N,
10
9 3
1
H nmr (deuteriochloroform): δ 7.19 (m, 1H), 7.36 (m, 1H), 8.63
20.67 Found: C, 59.57; H, 4.67; N, 20.38.
13
(m, 2H), 8.76 (d, J = 4.5 Hz, 2H), 9.60 (s,1H); C nmr: δ 120.2,
123.8, 133.5, 135.8, 150.2, 151.8, 157.8, 163.3; ms(EI): m/z MS
+
(EI): 157 (M , 100).
REFERENCES AND NOTES
Anal. Calcd. for C H N (157.17): C, 68.78; H, 4.49, N, 26.74.
9
7 3
Found: C, 68.71; H, 4.42; N, 26.65.
[1] F. Forman and I. Sucholeiki, J. Org. Chem. 60, 523 (1995).
[2] R. I. Elsenbauer and L. W. Schacklett, L. W. Handbook of
Conducting Polymers, Skotheim, T. A., Ed ; Marcel-Dekker : New
York, 1986, NY, Vol. 1, Chapter 7.
4-Methoxy-2-(3-pyridyl)pyrimidine (13).
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column chro-
matography using ethyl acetate/dichloromethane (50:50, v/v) as
eluent 109 mg (32%) of 13 as a colorless solid, mp 74°; H NMR
(deuteriochloroform): δ 4.05 (s, 3H), 6.83 (m, 1H), 7.14 (dd, J = 8.1,
4.5 Hz, 1H), 7.17 (d, J = 9.0 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H), 8.47
[3] D. S. Chemla and J. Zyss, Non Linear Optical Properties of
Organic Molecules and Crystals, Academic Press: Orlando, 1987.
[4a] V. Reiffenrath, J. Krause, H. J. Plach and G. Weber, Liq.
Cryst., 5, 159 (1989); [b] V. Reiffenrath and M. Bremer, Angew. Chem.
Int. Ed. Engl,. 33, 1386 (1994); [c] M. E. Glendenning, J. W. Goodby, M.
Hird and K. J. Toyne, J. Chem. Soc., Perkin Trans. 2, 481 (1999); [d] G.
W. Gray, M. Hird, D. Lacey, and K. J. Toyne, J Chem. Soc., Perkin Trans
2, 2041 (1989); [e] G. W. Gray, M. Hird and K. J. Toyne, Mol. Cryst. Liq.
Cryst.,204, 43 (1991); [f] M. Hird, K. J. Toyne, G. W. Gray, D. G.
McDonnel and I. Sage, C. Liq. Cryst., 18, 1 (1995); [g] G. W. Gray, M.
Hird, and K. J. Toyne, Mol. Cryst. Liq. Cryst.,195, 221 (1991); [h] F.
Toudic, A. Heynderickx, N. Plé, A. Turck and G. Quéguiner,
Tetrahedron, 59, 6375 (2003).
[5a] G. Chelucci, A. Cabras, A. Saba, A. and A. Sechi,
Tetrahedron: Asymetry, 7, 1027 (1996); [b] M. McCarthy and P. J. Guiry,
Tetrahedron, 57, 3809 (2001).
[6a] J.-M. Lehn, Angew. Chem.. Int. Ed. Engl,. 27, 89 (1988); [b]
J.-M Lehn, Supramolecular Chemistry, Concepts and Perspectives, VCH,
Weinheim, Germany (1995).
1
+
(d, J = 4.5 Hz, 1H), 8.63 (s, 1H); ms(EI): m/z 177 (M , 100).
Anal. Calcd. for C H N O (187.20): C, 64.16; H, 4.85, N,
10
9 3
22.45. Found: C, 64.18; H, 4.42; N, 22.26.
2,4-Di(3-pyridyl)pyrimidine (14) [27].
Cross-coupling reaction according the Procedure B with 3-
pyridylmagnesium chloride gave after purification by column
chromatography using ethyl acetate/isopropanol (90:10, v/v) as
eluent 91 mg (22%) of 14 as a yellow solid, mp 141-143°;
nmr (deuteriochloroform): δ 7.50 (m, 2H), 7.74 (d, J = 5.3 Hz,
1H) 8.58 (d, J =7.9 Hz, 1H), 8.80 (m, 3H), 8.96 (d, J = 5.3 Hz,
1
H
+
1H), 9.42 (s, 1H), 9.82 (s, 1H); ms(EI): m/z 234 (M , 100).

1428
L. Boully, M. Darabantu, A. Turck, N. Plé
Vol. 42
[7] G. Bringmann, R. Walter and R. Weirich, Angew. Chem. Int.
Ed. Engl., 29, 977 (1990).
[8] N. Miyaur and A. Suzuki, Chem. Rev. 95, 2457 (1995).
[9] V. Farina, Pure Appl. Chem. 68, 73 (1996).
[10] N. A. Bumagin and E. V. Luzikova, J. Organometal. Chem.
532, 271 (1997).
Organic Synthesis, John Wiley & Sons, New York, NY, 2002; [b] J.
Tsuji, Palladium Reagents and Catalysts: Innovations in Organic
Synthesis, John Wiley & Sons, New York, NY, 1996; [c] V. Bonnet, F.
Mongin, F. Trécourt, G. Breton, F. Marsais, G. Quéguine and P. Knochel,
Synlett, 1008 (2002).
[20a] A. Fürstner, A. Leitner, M. Mendez and H. Krause, J. Am.
Chem. Soc. 124, 13856 (2002); [b] J. Quintin, X. Franck, R. Hocquemiller
and B. Figadère, Tetrahedron Lett. 43, 3447, (2002).
[11a] F. Ullmann, Ber., 36, 2389 (1903); [b] E. Fanta, E, Synthesis, 1,
9-21(1974) .
[12a] M. Tiecco, L. Testaferri, M. Tingoli, D. Chianelli and M.
Montanucci, Synthesis, 736 (1974); [b] J. Hassan, M. Sévignon, C. Gozzi,
E. Schulz, and M. Lemaire, Chem. Rev. 102, 1359 (2002).
[13a] C. Gozzi, L. Lavenot, K. Ilg, V. Penalva and M. Lemaire,
Tetrahedron Lett., 38, 8867 (1997); [b] V. Penalva, J. Hassan, L. Lavenot,
C. Gozzi and M. Lemaire, Tetrahedron Lett., 39, 2559 (1998).
[14] J. J. Lafferty and F. H. Case, J. Org. Chem. 32, 1591 (1967).
[15a] H. Igeta, T. Tsuchiya, M. Nakajima and H. Yokogawa,
Tetrahedron Lett. 10, 2359 (1969); [b] H. Bleisinger, P. Scheidhauer, H.
Dürr, V. Wintgens, P. Valat and J. Kossanyi, J. Org. Chem. 63, 990 (1998);
[c] P. N. Baxter, J.-M. Lehn, G. Baum and D. Fenske, Chem. Eur. J. 4510
(2000).
[16] I. Murakoshi, T. Sekine, Y. Higushi, N. Ohyama and T.
Yamada, Chem. Pharm. Bull. 37, 1984 (1989).
[17a] D. D. Bly and M. G. Mellon, J. Org Chem. 27, 2945 (1962); [b]
J. Nasielski, A. Standaert and R. Nasielski-Hinkins, Synth. Commun. 21,
901 (1991); [c] P. Schwab, F. Fleischer and J. Michl, J. Org. Chem. 67, 443
(2002)
[21a] Y. Mettey and J.-M. Vierfond, J. Heterocyclic Chem. 23, 1051
(1986); [b] V. Bonnet, F. Mongin, F. Trécourt, G. Quéguiner and P.
Knochel, Tetrahedron, 58, 4429 (2002). [c] M. Feuerstein, H. Doucet and
M. Santelli, J. of Organometallic Chem. 687, 327 (2003).
[22a] O. Hinsberg and O. König, Ber. 24, 719 (1891); [b] H. J. Bock,
J. A. Naether and C. R.. Klaus, Helvetica Chimica Acta, 177, 1505 (1994).
[23a] J. P. Freeman, E. G. Duthie, M. J. O'Hare and J. F. Hansen, J.
Org. Chem. 17, 2756 (1972); [b] F.-L. Quing, R. Wang, B. Li, X. Zheng
and W.-D Meng, Journal of Fluorine Chem. 120, 21 (2003).
[24] J. M. Schomakerand, T. J. Delia, J. Org. Chem. 21, 7125
(2001).
[25] M. Hasebe, K. Kogawa and T. Tsuchiya, Tetrahedron Lett. 25,
3887 (1984).
[26] R. E. Van der Stoel and H. C. Van der Plas, J. Chem. Soc.;
Perkins Trans I, 1979, 2393.
[27] W. Scott, W. Fu, M.-K. Monahan and D. Bierer, Int. Appl.
2003, WO 03027100; Chem. Abstr., 138, 287694, (2003)
[28] S. Kazimierz and M. Serwin-Krajewska, Acta Poloniae
Pharmaceutica 28, 33 (1981).
[29] F. Bottari and S. Carboni, Gazzetta Chim. Italiana 87, 1281
(1957).
[18] J. G. Smith and J0 2002; [b] J. Tsuji, Palladium Reagents and
Catalysts: Innovations in Organic Synthesis, John Wiley & Sons, New
York, NY, 1996; [c] V. Bonnet, F. Mongin, F. Trécourt, G. Breton, F.
Marsais, G. Quéguine and P. Knochel, Synlett, 1008 (2002).
[19a] E. Negishi, Handbook of Organopalladium Chemistry for
[30] Y. Chen, 2002 Patent CN 1362409; Chem. Abstr., 140, 59650,
(2003).