2-Aminopyrimidine-4,6-diol as an efficient ligand for solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides

Article abstract of DOI:10.1021/jo061572q

Efficient and solvent-free copper-catalyzed N-arylations of imidazoles with aryl and heteroaryl halides have been demonstrated. In the presence of CuBr, 2-aminopyrimidine-4,6-diol, and TBAF (n-Bu₄NF), a variety of imidazoles underwent the N-arylation reaction with aryl and heteroaryl halides smoothly in moderate to excellent yields. Noteworthy is that the reaction is conducted under solvent-free conditions.

Full text of DOI:10.1021/jo061572q

2-Aminopyrimidine-4,6-diol as an Efficient
SCHEME 1
Ligand for Solvent-Free Copper-Catalyzed
N-Arylations of Imidazoles with Aryl and
Heteroaryl Halides
Ye-Xiang Xie, Shao-Feng Pi, Jian Wang, Du-Lin Yin, and
Jin-Heng Li*
Key Laboratory of Chemical Biology & Traditional Chinese
Medicine Research (Ministry of Education), College of
Chemistry and Chemical Engineering, Hunan Normal
UniVersity, Changsha 410081, China
greener processes, we expected to apply these ligands and base
in the N-arylation reaction. As expected, both aryl and heteroaryl
halides underwent the solvent-free N-arylation reaction with
imidazoles smoothly in the present of TBAF when a combina-
tion of CuBr and 2-aminopyrimidine-4,6-diol was employed as
the catalytic system (Scheme 1). In addition, it was found that
jhli@hunnu.edu.cn
ReceiVed July 28, 2006
5
DMF, the reported effective solvent, has a deleterious effect
on the reaction.
The N-arylation of imidazole (1a) with 1-bromo-4-methoxy-
benzene (2a) in the presence of 3 equiv of TBAF was studied
to identify a suitable catalyst and ligand. As shown in Table 1,
a number of pyrimidines as the ligand were first tested. The
results demonstrated that the reactivity of the ligands was
dependent on the substituents on the pyrimidine ring and that
(1) For selected recent examples, see: (a) Zhong, C.; He, J.; Xue, C.;
Li, Y. Bioorg. Med. Chem. 2004, 12, 4009. (b) Dyck, B.; Goodfellow, V.
S.; Phillips, T.; Grey, J.; Haddach, M.; Rowbottom, M.; Naeve, G. S.;
Brown, B.; Saunders, J. Bioorg. Med. Chem. Lett. 2004, 14, 1151. (c)
Smallheer, J. M.; Alexander, R. S.; Wang, J.; Wang, S.; Nakajima, S.; Rossi,
K. A.; Smallwod, A.; Barbera, F.; Burdick, D.; Luettgen, J. M.; Knabb, R.
M.; Wexler, R. R.; Jadhav, P. K. Bioorg. Med. Chem. Lett. 2004, 14, 5263.
Efficient and solvent-free copper-catalyzed N-arylations of
imidazoles with aryl and heteroaryl halides have been
demonstrated. In the presence of CuBr, 2-aminopyrimidine-
4
4,6-diol, and TBAF (n-Bu NF), a variety of imidazoles
(
d) Qiao, J. X.; Cheng, X.; Modi, D. P.; Rossi, K. A.; Luettgen, J. M.;
Knabb, R. M.; Jadhav, P. K.; Wexler, R. R. Bioorg. Med. Chem. Lett. 2005,
5, 29. (e) Mano, T.; Okumura, Y.; Sakakibara, M.; Okumura, T.; Tamura,
underwent the N-arylation reaction with aryl and heteroaryl
halides smoothly in moderate to excellent yields. Noteworthy
is that the reaction is conducted under solvent-free conditions.
1
T.; Miyamoto, K.; Stevens, R. W. J. Med. Chem. 2004, 47, 720. (f) Roppe,
J.; Smith, N. D.; Huang, D.; Tehrani, L.; Wang, B.; Anderson, J.; Brodkin,
J.; Chung, J.; Jiang, X.; King, C.; Munoz, B.; Varney, M. A.; Prasit, P.;
Cosford, N. D. P. J. Med. Chem. 2004, 47, 4645. (g) Venkatesan, A. M.;
Gu, Y.; Santos, O. D.; Abe, T.; Agarwal, A.; Yang, Y.; Petersen, P. J.;
Weiss, W. J.; Mansour, T. S.; Nukaga, M.; Hujer, A. M.; Bonomo, R. A.;
Knox, J. R. J. Med. Chem. 2004, 47, 6556. (h) Lange, J. H. M.; van
Stuivenberg, H. H.; Coolen, H. K. A. C.; Adolfs, T. J. P.; McCreary, A.
C.; Keizer, H. G.; Wals, H. C.; Veerman, W.; Borst, A. J. M.; de Looff,
W.; Verveer, P. C.; Kruse, C. G. J. Med. Chem. 2005, 48, 1823. (i) Quan,
M. L.; Lam, P. Y. S.; Han, Q.; Pinto, D. J. P.; He, M. Y.; Li, R.; Ellis, C.
D.; Clark, C. G.; Teleha, C. A.; Sun, J.-H.; Alexander, R. S.; Bai, S.;
Luettgen, J. M.; Knabb, R. M.; Wong, P. C.; Wexler, R. R. J. Med. Chem.
2005, 48, 1729. (j) Barch e´ chath, S. D.; Tawatao, R. I.; Corr, M.; Carson,
D. A.; Cottam, H. B. J. Med. Chem. 2005, 48, 6409. (k) Voets, M.; Antes,
I.; Scherer, C.; M u¨ ller-Vieira, U.; Biemel, K.; Barassin, C.; Marchais-
Oberwinkler, S.; Hartmann, R. W. J. Med. Chem. 2005, 48, 6632. (l)
Wiglenda, T.; Ott, I.; Kircher, B.; Schumacher, P.; Schuster, D.; Langer,
T.; Gust, R. J. Med. Chem. 2005, 48, 6516. (m) Jiang, W.; Guan, J.;
Macielag, M. J.; Zhang, S.; Qiu, Y.; Kraft, P.; Bhattacharjee, S.; John, T.
M.; Haynes-Johnson, D.; Lundeen, S.; Sui, Z. J. Med. Chem. 2005, 48,
2126.
N-Aryl imidazoles play an important role as structural and
functional units in many natural products and biologically active
1
compounds. Accordingly, many efficient and selective methods
2-7
have been provided for their synthesis. Recently, the copper-
catalyzed N-arylations of imidazoles with aryl halides promoted
by a ligand attracted much attention due to its economy and
3
-5
efficiency.
These highly efficient ligands included 1,10-
5a-d
5e-g
5h
phenanthroline derivatives,
amino acid derivatives,
-phosphonate, oxime-phosphine oxides, and phosphor-
amidite. Although these ligands combined with copper as
efficient catalytic systems for the N-arylations of imidazoles
with aryl iodides and bromides with a range of electronic and
steric properties are now extensively developed, only a few
catalysts extended the scope to both hindered substrates and
less active aryl halides (aryl bromides and aryl chlorides). In
particular, few papers on the N-arylations of imidazoles with
diamines,
8-hydroxyquinoline, pyrrolidine-
aminoarenethiol,
5i-k
5l
5
m
5n
2
5o
(2) For selected papers on the palladium-catalyzed N-arylations of
imidazoles, see: (a) Hartwig, J. F. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New
York, 2002; p 1051. (b) Jiang, L.; Buchwald, S. L. In Metal-Catalyzed
Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, Germany, 2004; p 699. (c) Bellina, F.; Cauteruccio, S.;
Mannina, L.; Rossi, R.; Viel, S. J. Org. Chem. 2005, 70, 3997.
5j,k,n-q
heteroaryl halides catalyzed by copper have been reported.
Moreover, harmful solvents were required in almost all cases.
5,8
Very recently, we found that pyrimidines were effective ligands
(3) For selected reviews on the use of copper as the catalyst, see: (a)
Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. ReV. 2004, 248, 2337.
9
to improve the palladium-catalyzed cross-coupling reactions.
(
b) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400.
On the other hand, we have also discovered that TBAF is a
suitable base for some solvent-free palladium-catalyzed cross-
(4) For a paper on the N-arylations of imidazoles with aryl halides
mediated by stoichiometric copper, see: Lindley, J. Tetrahedron 1984, 40,
1433.
1
0
couplings. As a continued interest in developing efficient and
10.1021/jo061572q CCC: $33.50 © 2006 American Chemical Society
8
324 J. Org. Chem. 2006, 71, 8324-8327
Published on Web 09/20/2006

TABLE 1. Screening Reaction Conditions for Copper-Catalyzed
N-Arylation of Imidazole (1a) with 1-Bromo-4-methoxybenzene (2a)a
2a, CuI, and TBAF afforded a trace amount of the corresponding
desired product 3 after 24 h (entry 1), whereas the yield of 3
was enhanced sharply to 68% in 24 h when 20 mol % of
2-aminopyrimidine-4,6-diol, a ligand, was added (entry 2). Other
ligands, such as L2 and L3 without a free hydroxyl group and
L4 having no amino group, gave the target product 3 under a
50% isolated yield (entries 3-5). Other copper compounds were
then evaluated (entries 6-8). We were happy to observe that
the yield of 3 was increased dramatically to 90% when CuBr
was used as the catalyst instead of CuI (entries 2 and 6).
However, both CuCl and Cu2O are inferior to CuI (entries 7
and 8). To our surprise, DMF, the reported effective solvent,5
suppressed the reaction (entries 6 vs 9). The effect of bases
was also investigated, and TBAF provided the best results
(entries 10-13). It was disclosed that the reaction temperature
had a fundamental influence on the reaction, and almost no
reaction was observed at 100 °C (entry 14).
The efficacy of the CuBr/L1/TBAF system for general
N-arylations of imidazoles with aryl and heteroaryl halides was
further evaluated, and the results are summarized in Table 2.
In the presence of CuBr (10 mol %), L1 (20 mol %), and TBAF
(3 equiv), the N-arylation of imidazole (1a) with aryl bromide
2
b or heteroaryl bromide 2c was conducted smoothly to afford
the corresponding products 4 and 5 in 96 and 80% yields,
respectively (entries 1 and 2). However, the reaction of substrate
1
a with chloride 2d was unsuccessful (entry 3). Gratifyingly,
we found that substrate 1a reacted efficiently with 2-chloro-
pyrimidine (2e), a heteroaryl chloride, in a 90% yield (entry
4). Encouraged by these results, a variety of aryl and heteroaryl
halides 2a-m was then treated with benzimidazole (1b) under
the standard reaction conditions (entries 5-17). The results
indicated that both aryl and heteroaryl halides all work well
with substrate 1b to generate the corresponding products in
moderate to excellent yields. For example, the less activated
bromide 2a was reacted with 1b in an 81% yield (entry 5). A
40% yield was still achieved even in the N-arylation of 1b with
chlorobenzene (2l) (entry 16). Satisfactory results were also
obtained for nitrogen- and/or sulfur-containing heteroaryl halides
a
Reaction conditions: 1a (1.0 mmol), 2a (1.2 mmol), [Cu] (10 mol %),
ligand (20 mol %) and TBAF (3 mmol) under Ar atmosphere at 145-150
C for 24 h. Isolated yield. DMF (1 mL) was added. Cs2CO3 (3 mmol)
b
c
d
°
e
f
instead of TBAF. KF (3 mmol) instead of TBAF. TEAC ((Et4N)2CO3;
g
3
mmol) instead of TBAF. Et3N (3 mmol) instead of TBAF. h At 100 °C.
(
entries 7, 9, 12-15, and 17). Gratifyingly, substrate 1c or 1d,
two hindered 2-methylimidazoles, underwent the N-arylation
2
-aminopyrimidine-4,6-diol (L1) bearing both hydroxyl and
reaction with 2c and/or 2e smoothly in good yields (entries 18-
amino group was the most effective ligand (entries 1-5).
Without the aid of any ligands, treatment of substrate 1a with
(6) For selected representative papers on the copper-catalyzed N-
arylations of imidazoles with other reagents, see: (a) Lopez-Alvarado, P.;
Avenda n˜ o, C.; Men e´ ndez, J. C. J. Org. Chem. 1995, 60, 5678. (b) Collman,
J. P.; Zhong, M. Org. Lett. 2000, 2, 1233. (c) Collman, J. P.; Zhong, M.;
Zeng, L.; Costanzo, S. J. Org. Chem. 2001, 66, 1528. (d) Collman, J. P.;
Zhong, M.; Zhang, C.; Costanzo, S. J. Org. Chem. 2001, 66, 7892. (e)
Lan, J.-B.; Chen, L.; Yu, X.-Q.; You, J.-S.; Xie, R.-G. Chem. Commun.
2004, 188. (f) Lam, P. Y. S.; Deudon, S.; Averill, K. M.; Li, R.; He, M.
Y.; DeShong, P.; Clark, C. G. J. Am. Chem. Soc. 2000, 122, 7600. (g)
Fedorov, A. Y.; Finet, J.-P. Tetrahedron Lett. 1999, 40, 2747. (h) Kang,
S.-K.; Lee, S.-H.; Lee, D. Synlett 2000, 1022. (i) Lam, P. Y. S.; Clark, C.
G.; Saubern, S.; Adams, J.; Averill, K. M.; Chan, D. M. T.; Combs, A.
Synlett 2000, 674.
(7) For selected recent papers on the synthesis of N-aryl imidazoles via
other transformations, see: (a) Lee, S.-H.; Yoshida, K.; Matsushita, H.;
Clapham, B.; Koch, G.; Zimmermann, J.; Janda, K. D. J. Org. Chem. 2004,
69, 8829. (b) Li, W.; Lam, Y. J. Comb. Chem. 2005, 7, 644. (c) Gracias,
V.; Gasiecki, A. F.; Djuric, S. W. Org. Lett. 2005, 7, 3183. (d) Szczepank-
iewicz, B. G.; Rohde, J. J.; Kurukulasuriya, R. Org. Lett. 2005, 7, 1833.
(e) Siamaki, A. R.; Arndtsen, B. A. J. Am. Chem. Soc. 2006, 128, 6050.
(8) For a paper on the solvent-free copper-catalyzed amination reactions
of aryl halides with amines, see: Gajare, A. S.; Toyota, K.; Yoshifuji, M.;
Ozawa, F. Chem. Commun. 2004, 1994.
(5) For papers on the copper-catalyzed N-arylations of imidazoles with
aryl halides, see: (a) Kiyomori, A.; Marcoux, J. F.; Buchwald, S. L.
Tetrahedron Lett. 1999, 40, 2657. (b) Kuil, M.; Bekedam, E. K.; Visser,
G. M.; van den Hoogenband, A.; Terpstra, J. W.; Kamer, P. C. J.; Kamer
van Leeuwen, P. W. N. M.; van Strijdonck, G. P. F. Tetrahedron Lett. 2005,
4
6, 2405. (c) Altman, R. A.; Buchwald, S. L. Org. Lett. 2006, 8, 2779. (d)
Kuil, M.; Bekedam, E. K.; Visser, G. M.; van den Hoogenband, A.; Terpstra,
J. W.; Kamer, P. C.; van Leeuwen, P. W. N. M.; van Strijdonck, G. P. F.
Tetrahedron Lett. 2005, 46, 2405. (e) Klapars, A.; Antilla, J. C.; Huang,
X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727. (f) Alcalde, E.;
Dinar e` s, I.; Rodr ´ı guez, S.; Garcia de Miguel, C. Eur. J. Org. Chem. 2005,
1
637. (g) Antilla, J. C.; Baskin, J. M.; Barder, T. E.; Buchwald, S. L. J.
Org. Chem. 2004, 69, 5578. (h) Jerphagnon, T.; van Klink, G. P. M.; de
Vries, J. G.; van Koten, G. Org. Lett. 2005, 7, 5241. (i) Ma, D.; Cai, Q.
Synlett 2004, 128. (j) Zhang, H.; Cai, Q.; Ma, D. J. Org. Chem. 2005, 70,
5
164. (k) Lv, X.; Wang, Z.; Bao, W. Tetrahedron 2006, 62, 4756. (l) Liu,
L.; Frohn, M.; Xi, N.; Dominguez, C.; Hungate, R.; Reider, P. J. J. Org.
Chem. 2005, 70, 10135. (m) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org.
Chem. 2005, 70, 8107. (n) Xu, L.; Zhu, D.; Wu, F.; Wang, R.; Wan, B.
Tetrahedron 2005, 61, 6553. (o) Zhang, Z.; Mao, J.; Zhu, D.; Wu, F.; Chen,
H.; Wan, B. Tetrahedron 2006, 62, 4435. (p) Choudary, B. M.; Sridhar,
C.; Kantam, M. L.; Venkanna, G. T.; Sreedhar, B. J. Am. Chem. Soc. 2005,
(9) (a) Li, J.-H.; Zhang, X.-D.; Xie, Y.-X. Synlett 2005, 1897. (b) Li,
J.-H.; Zhang, X.-D.; Xie, Y.-X. Eur. J. Org. Chem. 2005, 4256.
(10) (a) Li, J.-H.; Deng, C.-L.; Xie, Y.-X. Synthesis 2006, 969. (b) Liang,
Y.; Xie, Y.-X.; Li, J.-H. J. Org. Chem. 2006, 71, 379.
1
2
27, 9948. (q) Son, S. U.; Park, I. K.; Park, J.; Hyeon, T. Chem. Commun.
004, 778.
J. Org. Chem, Vol. 71, No. 21, 2006 8325

TABLE 2. N-Arylations of Imidazoles (1) with Aryl or Heteroaryl
SCHEME 2
a
Halides (2) in the Presence of CuBr, L1, and TBAF
2
0). However, the N-arylation of 2-phenylimidazole (1e) was
unsuccessful (entries 21 and 22). For example, treatment of
substrate 1e with the activated bromide 2b, CuBr (10 mol %),
L1 (20 mol %), and TBAF (3 equiv) provided the target product
1
9 in a low yield (a 30% isolated yield; entry 21).
As described in Scheme 2, we have formulated a working
mechanism for the solvent-free copper-catalyzed N-arylations
of imidazoles that is based on the previously proposed mech-
3,5,11,12
anism.
The chelation of Cu(I) with an 2-aminopyrimidine-
4
,6-diol occurs to make the Cu(I) species more reactive toward
12
oxidative addition and/or stabilized intermediate B that was
generated from the oxidative addition of A with aryl halides.
In the presence of base, imidazoles reacted with intermediate
B readily to afford intermediate C, followed by reductive
elimination to provide the desired product and regenerate the
active Cu(I) species. We inferred that CuBr is the best catalyst
for the present reaction by virtue of its insensitivity to light
and air. Study of the accurate mechanism is in progress.
In summary, we have disclosed that 2-aminopyrimidine-4,6-
diol acted as an efficient and general ligand for the solvent-
free copper-catalyzed N-arylations of imidazoles, including
2
-substituted imidazoles, with a diverse range of aryl and
heteroaryl halides providing moderate to excellent yields. It is
noteworthy that the present reaction is conducted under solvent-
free conditions. Moreover, the presence of DMF has a deleteri-
ous effect on the reaction. Overall, the present protocol
significantly advances the scope of N-arylations of imidazoles
and is of great value to the research and development efforts in
the pharmaceutical industry. Efforts to extend the applications
of the CuBr/pyrimidine/TBAF system in the formation of other
C-N bond transformations are currently underway in our
laboratory.
Experimental Section
Typical Experimental Procedure for the Solvent-Free Cop-
per-Catalyzed N-Arylation of Imidazoles. A mixture of imidazole
1
2
(1.0 mmol), aryl halide 2 (1.2 mmol), CuBr (10 mol %),
-aminopyrimidine-4,6-diol (L , 20 mol %), and TBAF (3 mmol)
1
(11) (a) Lindley, J. Tetrahedron 1984, 40, 1433. (b) Cohen, T.; Wood,
J.; Dietz, A. G., Jr. Tetrahedron Lett. 1974, 15, 3555. (c) Paine, A. J. J.
Am. Chem. Soc. 1987, 109, 1496. (d) Aalten, H. L.; van Koten, G.; Grove,
D. M.; Kuilman, T.; Piekstra, O. G.; Hulshof, L. A.; Sheldon, R. A.
Tetrahedron 1989, 45, 5565.
a
Reaction conditions: 1 (1 mmol), 2 (1.2 mmol), CuBr (10 mol %), L1
(
2
20 mol %), and TBAF (3 mmol) under Ar atmosphere at 145-150 °C for
b
(12) Zhang, S.; Zhang, D.; Liebeskind, L. S. J. Org. Chem. 1997, 62,
4 h. Isolated yield.
326 J. Org. Chem., Vol. 71, No. 21, 2006
2
312.
8

was stirred at 145-150 °C for 24 h until complete consumption of
starting material was monitored by TLC. After the reaction was
finished, ethyl acetate was poured into the mixture, then washed
with water, extracted with diethyl ether, dried over anhydrous
δ 158.3, 157.2, 152.7, 142.7, 134.0, 123.4, 119.0, 118.0, 114.4,
+
18.4; LRMS (EI, 20 eV) m/z (%) 210 (M , 100); HRMS (EI) for
+
C
12
H
10
N
4
(M ) calcd 210.0906, found 210.0905.
2-(2-Methyl-1H-imidazol-1-yl)pyrimidine (18): Slight yellow
1
2 4
Na SO , and evaporated under vacuum, and the residue was purified
solid, mp 90.3-90.8 °C (uncorrected); H NMR (500 MHz, CDCl
3
)
by flash column chromatography (ethyl acetate or hexane/ethyl
acetate) to afford the desired product.
δ 8.75-8.70 (m, 2H), 7.85 (d, J ) 6.0 Hz, 1H), 7.19 (t, J ) 9.7
13
Hz, 1H), 6.96 (d, J ) 7.5 Hz, 1H), 2.81 (s, 3H); C NMR (100
MHz, CDCl
1
-(Pyrimidin-2-yl)-1H-benzimidazole (10): White solid, mp
3
) δ 158.4, 156.3, 146.7, 127.5, 118.4, 118.2, 18.0;
1
+
1
1
08.4 °C (uncorrected); H NMR (500 MHz, CDCl
3
) δ 9.11 (s,
LRMS (EI, 20 eV) m/z (%) 160 (M , 100); HRMS (EI) for C
8 8
H N
4
+
H), 8.79 (d, J ) 4.8 Hz, 2H), 8.62 (t, J ) 8.0 Hz, 1H), 7.87 (d,
(M ) calcd 160.0749, found 160.0747.
13
J ) 7.8 Hz, 1H), 7.46-7.38 (m, 2H), 7.23 (t, J ) 5.0 Hz, 1H);
C
NMR (125 MHz, CDCl
3
) δ 158.5, 156.4, 145.1, 141.8, 131.9, 124.6,
Acknowledgment. The authors thank the National Natural
Science Foundation of China (No. 20572020), Hunan Provincial
Natural Science Foundation of China (No. 05JJ1002), Fok Ying
Dong Education Foundation (No. 101012), the Key Project of
Chinese Ministry of Education (No. 206102), and Scientific
Research Fund of Hunan Provincial Education Department (No.
+
1
1
1
23.8, 120.4, 118.0, 115.6; LRMS (EI, 20 eV) m/z (%) 196 (M ,
00); HRMS (EI) for C11
96.0749.
+
8 4
H N (M ) calcd 196.0749, found
1
-(Thiazol-2-yl)-1H-benzimidazole (15): Yellow solid, mp
1
1
1
7
1
(
(
00.9 °C (uncorrected); H NMR (500 MHz, CDCl
H), 8.11 (d, J ) 8.1 Hz, 1H), 7.90 (s, 1H), 7.72 (s, 1H), 7.49-
.41 (m, 2H), 7.26 (s, 1H); 13C NMR (125 MHz, CDCl
) δ 157.1,
44.2, 141.2, 140.5, 131.9, 125.0, 124.1, 121.0, 115.1, 112.3; LRMS
3
) δ 8.59 (s,
0
5B038) for financial support.
3
Supporting Information Available: Analytical data and spectra
H and C NMR) for products 3-19, and typical procedure for
+
7 3
EI, 20 eV) m/z (%) 201 (M , 100); HRMS (EI) for C10H N S
(1
13
+
M ) calcd 201.0361, found 201.0360.
-Methyl-1-(pyrimidin-2-yl)-1H-benzimidazole (17): Slight
the solvent-free copper-catalyzed N-arylation of imidazoles. This
material is available free of charge via the Internet at
http://pubs.acs.org.
2
1
yellow solid, mp 77.3 °C (uncorrected); H NMR (500 MHz,
CDCl ) δ 8.81 (s, 2H), 8.26 (t, J ) 3.0 Hz, 1H), 7.74-7.72 (m,
H), 7.33-7.22 (m, 3H), 2.97 (s, 3H); 1 C NMR (125 MHz, CDCl
3
3
1
3
)
JO061572Q
J. Org. Chem, Vol. 71, No. 21, 2006 8327