Synthesis and properties of pyrimidine-containing linear molecules

Article abstract of DOI:10.1016/S0040-4039(01)01275-8

Palladium-catalyzed Stille and Sonogashira coupling reactions were sequentially applied for constructing novel pyrimidine-containing linear molecules. The chemoselectivity of 5-bromo-2-iodopyrimidine (1) towards Pd-catalyzed coupling reaction serves as a

Full text of DOI:10.1016/S0040-4039(01)01275-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6341–6344
Synthesis and properties of pyrimidine-containing linear
molecules
Ken-Tsung Wong,* Yun-Ruei Lu and Yuan-Li Liao
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Received 24 April 2001; revised 13 July 2001; accepted 17 July 2001
Abstract—Palladium-catalyzed Stille and Sonogashira coupling reactions were sequentially applied for constructing novel
pyrimidine-containing linear molecules. The chemoselectivity of 5-bromo-2-iodopyrimidine (1) towards Pd-catalyzed coupling
reaction serves as a tool for the successful control of the arrangement of dipolar pyrimidine moieties inside the conjugated
backbone. The influence of the arrangement of dipolar pyrimidine in the linear backbone on their absorption and photolumines-
cence are not stupendous. Thermogravimetric analysis (TGA) indicate that all linear molecules in this study exhibit high thermal
stability. © 2001 Elsevier Science Ltd. All rights reserved.
Rigid and rod-like molecules with extended p-conjuga-
tion are of interest due to their potential use in nano-
scale electronics, e.g. molecular wires.1 Modifications of
the primary properties of these well-defined linear sys-
tems have been achieved by introducing a functional
moiety as a conjugated subunit or as a terminal group.
For example, better electron delocalization along the
molecular axis can be achieved by introducing a redox-
active transition metal as the central linkage.2 The
introduction of a photoactive moiety into the p-conju-
gated skeleton has also been found to perform a switch
function.3 Heteroaromatics with potential coordinating
ability have also been introduced as a part of the
conjugated backbone4 or as terminal groups.5 In this
paper, we report the synthesis of linear molecules con-
taining pyrimidine subunits in the conjugated backbone
of the molecule. Due to the high electron affinity,6 the
presence of the pyrimidine moiety in a p-conjugated
system could create a new class of compounds with
high electron accessibility. Alternatively, control on the
arrangement of the dipolar pyrimidine moiety in a
defined p-conjugated system could serve as an addi-
tional tool for tuning the physical properties.
lectively at the C2 position. The bromo substituent at
the C5 position remains intact, allowing a consecutive
coupling reaction with either arylboronic acids or ter-
minal alkynes, using the same Pd-catalyst.8 Therefore,
the dipolar orientation of the pyrimidine group in a
linear conjugated system can be controlled by taking
advantage of the difference in reactivity at C2 and C5
positions of 1. In our previous report,8 we have shown
that the photophysical properties of a p-conjugated
system with alternating triple bonds and aromatic rings
were found to be irrespective of the difference in
arrangement of the dipolar pyrimidine moiety. And, the
molecules prefer to have a coplanar conformation in
the ground state due to the lack of ortho–ortho steric
interactions between the two aromatic rings, which are
separated by a triple bond. However, in the case of a
conjugated molecule containing a pyrimidine group
attached to the phenyl ring, the physical properties
could depend on the different arrangement of the
pyrimidine unit in the backbone.
Compound 3 was obtained by the Pd-catalyzed cou-
pling of the pyrimidine derivative 1 with metallo-com-
pounds of the type 2, in which the trimethylsilylethynyl
group serves as a masked reaction site for the further
extension of p-conjugation. Compounds of the type 2
with different metallo substituents were tested for their
coupling efficiency with 1 in the presence of various
Pd-catalysts (cf. Table 1). Reaction of compound 1 with
2 (M=ZnCl) in the presence of PdCl2(dppf) or
PdCl2(PPh3)2 as catalyst (entries 1 and 2, Table 1)
resulted in the recovery of 1. Treating 1 with 2 (M=
MgBr) in the presence of a catalytic amount of
Under mild conditions, Pd-catalyzed coupling reactions
of 5-bromo-2-iodopyrimidine (1) with arylboronic
acids7 (Suzuki coupling) or terminal alkynes7,8 (Sono-
gashira reaction) have been found to proceed chemose-
Keywords: pyrimidine; molecular wire; Sonogashira coupling.
* Corresponding author. Tel.: +886-2-2363-0231 ext. 3315; fax: +886-
2-2363-6359; e-mail: kenwong@ccms.ntu.edu.tw
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01275-8

6342
K.-T. Wong et al. / Tetrahedron Letters 42 (2001) 6341–6344
Table 1. Pd-catalyzed coupling reactions of 1 with metallo compound 2
N
N
Pd-catalyst
solvent
N
N
+
Br
I
M
SiMe3
Br
SiMe3
1
2
3
Entry
2 (M=)
Pd-catalyst
Solvent (temperature, °Ca)
3 Yield (%)b
1
2
3
4
5
6
7
ZnCl
ZnCl
PdCl2(dppf)
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2/Ag2O
Pd(PPh3)4
THF (80)
THF (80)
THF (80)
DMF (160)
DMF (160)
DMF (160)
PhCH3 (120)
0
0
3
48
23
6
MgBr
SnBu3
SnBu3
SnBu3
SnBu3
PdCl2(PPh3)2
63
a Temperature of oil bath.
b Isolated yield.
PdCl2(PPh3)2 in refluxing THF led to the formation of
3, but in a very low yield (3%, entry 3, Table 1). In
DMF, Sn-derivative 2 (M=SnBu3) coupled with 1
more efficiently in the presence of PdCl2(PPh3)2 to
afford 3 in 48% yield. However, by changing the cata-
lyst system from PdCl2(PPh3)2 to Pd(PPh3)4 or by car-
rying out the reaction in the presence of Ag2O,9 the
yields of 3 were found to be further reduced (entries 5
and 6, Table 1). Finally, it was found that by changing
the reaction solvent from DMF to toluene, the yield of
3 could be increased to 63%. The lack of ortho–ortho
interactions between the pyrimidine ring and the phenyl
ring could be beneficial for increasing the conjugation
length of 3 in the ground state.
ence of 2N NaOH in MeOH/THF (3:1) at room tem-
perature to afford compound 10 in 77% yield. The
Sonogashira coupling procedure used for the synthesis
of 12 resulted in complex products, hence the procedure
was slightly modified to obtain 12. Thus, three equal
portions of 10 in THF was added every 4 h to the
refluxing THF solution of the diiodo compound 11 in
i
the presence of Pd(PPh3)4, CuI and Pr2NH to yield 12
(45%).11 From the above facts, it is evident that the
conjugation length as well as the arrangement of the
dipolar pyrimidine moieties in the conjugated backbone
could be manipulated by employing different reaction
sequences.
Optical absorption and photoluminescence studies were
carried out on the pyrimidine-containing molecules 5a,
5b, 7a, 7b, and 12 (cf. Table 2). Due to the electron-
donating property, the introduction of the dioctyloxy
side chains leads to a significant red-shift in the elec-
tronic absorption and the emission maxima compared
to that of the linear molecules with dioctyl side chains
(5a versus 5b and 7a versus 7b). The compounds 5a, 5b,
7a, 7b, and 12 show very intense blue fluoresence with
high quantum yields upon irradiation at their absorp-
tion maxima. Dilute solutions of 5b and 7b in EtOAc
and CHCl3, exhibit similar absorption and emission
spectra irrespective of the difference in the dipolar
orientation of the pyrimidine moiety in the backbone.
However, 5a and 7a show different emission maxima in
EtOAc. Especially, dilute solution of 7a in EtOAc
shows solvatochromic behavior with an emission maxi-
mum at 389 nm and a shoulder at 409 nm. In CHCl3
the emission maximum of 7a is red shifted to 402 nm
with a shoulder at 423 nm. But, in CHCl3, the differ-
ence in the emission maxima of 5a and 7a is less than
that in EtOAc. Interestingly, 5b, 7b, and 12 show a
similar behavior in their absorption and emission max-
ima. Based on the structure, one would expect 12 to
have a longer conjugation length compared with those
of 5b and 7b; however, the photophysical studies indi-
cate that the p-conjugation of 12 along the molecular
axis is ‘saturated’ and not longer than that of 5b and
7b.
The conjugation length of 3 was extended by a Sono-
gashira coupling reaction by treating 3 with the
i
dialkyne 4a or 4b in the presence of Pr2NH and
catalytic amounts of Pd(PPh3)4 and CuI in refluxing
THF10 to yield the linear compounds 5a and 5b in 71
and 68%, respectively (Scheme 1). Changing the orien-
tation of the pyrimidine group in 5 could be achieved
by treating the dialkyne 4 with 1 to afford 6,8 followed
by a Stille coupling reaction with 2 (M=SnBu3) in the
presence of PdCl2(PPh3)2. Accordingly, the linear
molecules 7a and 7b, which have the same p-conjugated
backbone as that of 5a and 5b but with a different
arrangement of the pyrimidine moieties were isolated in
48 and 45% yield, respectively. However, due to the
ortho–ortho interaction between the pyrimidine ring and
the phenyl ring in 7a and 7b could result in a non-
coplanar conformation in the ground state. The termi-
nal trimethylsilylethynyl groups in 5a and 5b, as well as
in 7a and 7b can be removed by standard desilylation
procedures, resulting in the formation of new reaction
sites, which provide the possibilty for further modifying
the end groups of the linear molecules 5a, 5b, 7a and
7b.
Another approach towards increasing the conjugation
length was achieved by treating 3 with alkyne 8 using a
Sonogashira coupling reaction to obtain 9 in 65% yield.
The trimethylsilyl group in 9 was cleaved in the pres-

K.-T. Wong et al. / Tetrahedron Letters 42 (2001) 6341–6344
6343
R
N
N
4
R
Br
SiMe3
Pd(PPh3)4, CuI
iPr2NH, THF, 80 oC
Me3Si
R
3
N
N
N
N
SiMe3
R
5a, R = C8H17, 71%
5b, R = OC8H17, 68%
R
R
Bu3Sn
SiMe3
N
N
N
N
4
2
R
Br
I
Br
Br
PdCl2(PPh3)2
PhCH3, reflux, 120 oC
N
1
N
Pd(PPh3)4, CuI
iPr2NH, THF
R
6a, R = C8H17
6b, R = OC8H17
R
N
N
N
Me3Si
SiMe3
N
R
7a, R = C8H17, 46%
7b, R = OC8H17, 41%
N
N
N
8
Br
SiMe3
SiMe3
N
Pd(PPh3)4, CuI
3
9
iPr2NH, THF, 80 oC
65%
OC8H17
I
I
N
11
2N NaOH
C8H17O
H
9
N
THF/CH3OH
77%
Pd(PPh3)4, CuI
iPr2NH, THF, 80 oC
45%
10
OC8H17
N
N
N
N
C8H17O
12
Scheme 1.
Table 2. Physical properties of pyrimidine-containing linear molecules 5a, 5b, 7a, 7b, and 12
Compound
umax (nm) in EtOAc
uem (nm) in EtOAc
uem (nm) in CHCl3
Quantum yield (%)a
Td (°C)b
5a
5b
7a
7b
12
362
332, 394
357
331, 396
387
398, 421
449c
407, 427
449
402, 423
454
87
62
67
66
35
359, 459
348, 434
467
308, 423
372, 426
389, 409
454c
450
455
a In EtOAc, Coumarin I was employed as standard.
b Detected by TGA.
c The excitation spectra of 5b and 7b are similar to their absorption spectra, the emission spectra were recorded upon excitation at 394 nm for
5b and 396 nm for 7b.

6344
K.-T. Wong et al. / Tetrahedron Letters 42 (2001) 6341–6344
Thermal stability of 5a, 5b, 7a, 7b and 12 was investi-
gated by TGA. No decomposition was observed below
300°C, and the decomposition temperatures (Td) are
summarized in Table 2. The TG thermograms reveal
that complete weight loss occurs before 500°C, which
corresponds to the removal of the alkyl or alkoxy side
chains. The residue is stable without any further
decomposition up to 800°C. The high thermal stability
of the residue could be attributed to the thermal cross-
linking of the conjugated backbone.
Soc. 2000, 122, 7195–7201; (c) Fernandez-Acebes, A.;
Lehn, J.-M. Chem. Eur. J. 1999, 5, 3285–3292.
4. Khatyr, A.; Ziessel, R. J. Org. Chem. 2000, 65, 7814–7824.
5. Harriman, A.; Ziessel, R. Chem. Commun. 1996, 1707–
1716.
6. (a) Gammper, R.; Mari, H.-J.; Polborn, K. Synthesis 1997,
696–718; (b) Kanbara, T.; Kushida, T.; Saito, N.; Kuwa-
jima, I.; Kubota, K.; Yamamoto, T. Chem. Lett. 1992,
583–586.
7. Goodby, J. W.; Hird, M. H.; Lewis, R. A.; Toyne, K. J.
Chem. Commun. 1996, 2719–2720.
In summary, we have established an efficient pathway
for introducing the highly electronegative pyrimidine
moiety into a p-conjugated backbone affording a new
class of linear molecules. Control on the dipolar orien-
tation of pyrimidine in the conjugated backbone was
accomplished by taking advantage of the different reac-
tivities at the C2 and C5 position of 1. However, the
photophysical studies indicate that the difference in the
arrangement of the pyrimidine moiety in the p-conju-
gated system has a slight influence on their properties.
8. Wong, K.-T.; Hsu, C. C. Org. Lett. 2001, 3, 173–175.
9. Malm, J.; Bjo¨rk, P.; Gronowitz, S.; Ho¨rnfeldt, A.-B.
Tetrahedron Lett. 1992, 33, 2199–2202.
10. An improved procedure for Sonagashira coupling: Tho-
rand, S.; Krause, N. J. Org. Chem. 1998, 63, 855–8553.
11. New compounds were characterized by spectroscopic tech-
niques. Selected data: Compound 3: 1H NMR (CDCl3, 400
MHz) l 8.83 (s, 2H), 8.35 (d, J=8.8 Hz, 2H), 7.51 (d,
J=8.8 Hz, 2H), 0.27 (s, 9H), Anal. calcd for C15H15BrN2Si:
C, 54.38; H, 4.56; N, 8.46, found: C, 54.23; H, 4.65; N, 8.41.
Compound 5a: 1H NMR (CDCl3, 400 MHz) l 8.90 (s, 4H),
8.42 (d, J=7.4 Hz, 4H), 7.60 (d, J=7.4 Hz, 4H), 7.43 (s,
2H), 2.83 (t, J=7.6 Hz, 4H), 1.52–1.55 (m, 4H), 1.29–1.33
(m, 20H), 0.87–0.89 (m, 6H), 0.28 (s, 9H); Anal. calcd for
C56H66N4Si2: C, 79.01; H, 7.81; N, 6.58, found: C, 78.90;
Acknowledgements
1
This work was supported by the National Science
Council of Taiwan (NSC-88-2113-M002-036, NSC-89-
2113-M002-008). We thank Professor Hsiu-Fu Hsu and
Dr. Jo¨rn Wirsching for their suggestive discussion on
the preparation of the manuscript.
H, 7.68; N, 6.63. Compound 5b: H NMR (CDCl3, 400
MHz) l 8.90 (s, 4H), 8.40 (d, J=8 Hz, 4H), 7.60 (d, J=8
Hz, 4H), 7.06 (s, 2H), 4.06 (t, J=6.6 Hz, 4H), 1.92–1.95
(m, 4H), 1.29–1.33 (m, 20H), 0.87–0.90 (m, 6H), 0.28 (s,
9H); Anal. calcd for C56H66N4O2Si2: C, 76.14; H, 7.53; N,
6.34, found: C, 75.93; H, 7.55; N, 6.38. Compound 7a: l
8.97 (s, 4H), 7.62 (d, J=8.6 Hz, 4H), 7.57 (d, J=8.6 Hz,
4H), 7.57 (s, 2H), 2.91 (t, J=7.5 Hz, 4H), 1.73 (m, 4H),
1.25–1.41 (m, 20H), 0.84–0.87 (m, 6H), 0.28 (s, 9H); Anal.
calcd for C56H66N4Si2: C, 79.01; H, 7.81; N, 6.58, found:
C, 79.30; H, 7.98; N, 6.53. Compound 7b: 1H NMR
(CDCl3, 400 MHz) l 8.95 (s, 4H), 7.61 (d, J=6.5 Hz, 4H),
7.56 (d, J=6.5 Hz, 4H), 7.17 (s, 2H), 4.04 (t, J=6.7 Hz,
4H), 1.84–1.88 (m, 4H), 1.26–1.35 (m, 20H), 0.87–0.87 (m,
6H), 0.27 (s, 9H); Anal. calcd for C56H66N4O2Si2: C, 76.14;
H, 7.53; N, 6.34, found: C, 76.03; H, 7.65; N, 6.48.
Compound 12: 1H NMR (CDCl3, 400 MHz) l 8.90 (s, 4H),
8.46 (d, J=8.0 Hz, 4H), 7.67 (d, J=8.0 Hz, 4H), 7.52 (d,
J=8.4 Hz, 4H), 7.42 (d, J=8.4 Hz, 4H), 7.05 (s, 2H), 4.07
(t, J=6.2 Hz, 4H), 1.92–1.95 (m, 4H), 1.29–1.33 (m, 20H),
0.87–0.90 (m, 6H); Anal. calcd for C70H74N4O2: C, 83.79;
H, 7.43; N, 5.58, found: C, 83.67; H, 7.25; N, 5.33.
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