Rhenium tricarbonyl complexes of 1-benzyl-4-(5-bipyridyl)-1H-1,2,3- triazoles

Article abstract of DOI:10.1016/j.ica.2010.04.019

Copper(l) catalyzed [3+2] cycloaddition reactions between 5-ethynylbipyridine and benzyl, p-methylbenzyl, or m-bromobenzyl azides yields the corresponding l-benzyl-4-(5-bipyridyl)-lH-l,2,3-triazoles 1-3. Reaction between 1-3 and [NEt₄J₂

Full text of DOI:10.1016/j.ica.2010.04.019

Inorganica Chimica Acta 363 (2010) 2520–2525
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Rhenium tricarbonyl complexes of 1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazoles
*
Catherine Cote, Rein U. Kirss
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Copper(I) catalyzed [3+2] cycloaddition reactions between 5-ethynylbipyridine and benzyl, p-methyl-
benzyl, or m-bromobenzyl azides yields the corresponding 1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazoles
1–3. Reaction between 1–3 and [NEt4]2[Re(CO)3Br3] yields the [1-benzyl-4-(5-bipyridyl)-1H-1,2,3-tria-
zole]Re(CO)3Br complexes 4–6. The Re(CO)3Br complexes of 5- and 6-ethynylbipyridine complexes (7–
8) are prepared in a similar fashion. Cycloaddition reactions between 7 and benzyl azide yields mixtures
of 4 and unreacted starting material.
Received 20 January 2010
Received in revised form 10 April 2010
Accepted 13 April 2010
Available online 20 April 2010
Keywords:
Cu(I) catalyzed [3+2] cycloaddition
reactions
Ó 2010 Elsevier B.V. All rights reserved.
Rhenium complexes
Bipyridine complexes
1. Introduction
substituted benzyl azides as a ‘‘proof of concept” for future efforts
toward the preparation of BFCA’s bearing the bipyridyl moiety as
The coordination chemistry of rhenium is relevant to the bio-
medical community since rhenium compounds can be used as
models for analogous 99mTc complexes useful in a broad range of
imaging applications [1,2]. Coordination compounds containing
radioactive isotopes of rhenium (e.g. 186Re and 188Re) have also
been investigated as therapeutic agents for bone and other cancer
[2b,3]. A recurrent theme in this research is the ongoing search for
bifunctional chelating agents (BFCA) [2], which consist of a target-
ing molecule, a linker and a chelating ligand for the metal or radio-
nuclide. The targeting molecule can include hormones [4], peptides
[5], fatty acids [6], and carbohydrates [7]. Among the linkers that
have been explored are hydrocarbon chains [4], polyethers [8]
and polypeptides [2,5]. Amino acids [9], pyridyl amines [10], thio-
ethers [11], phosphates [12] and peptide nucleic acids [13] have all
been reported as chelating groups for Re and Tc in BFCA’s. From the
perspective of chemical synthesis, the preparation of BFCA’s should
proceed rapidly, in high yield and with a minimum number of
steps. The coordination of the metal should be the final step and
have a large formation constant.
the chelating ligand (Scheme 1). We also describe the synthesis
and characterization of rhenium carbonyl derivatives of the new
triazole ligands as well as our explorations of copper-catalyzed
‘‘click” chemistry of (ethynylbipyridine)Re(CO)3Br coordination
compounds.
2. Experimental
Bromobipyridines [14], ethynylbipyridines [15] organic azides
[16] and [NEt4]2Re(CO)3Br3] [17] were prepared by literature pro-
cedures. Elemental analyses (C, H, N) were performed by Columbia
Analytical Services, Inc. NMR spectra were recorded at 300 and
400 MHz for 1H and 75.4 and 100.7 MHz for 13C{1H} on a Varian
Mercury VX300 and Varian Mercury VX400 spectrometers. Proton
chemical shifts are reported relative to residual protons in the sol-
vent (CHCl3 at d 7.24 ppm, CHDCl2 or CD3COCD2H at d 2.05 ppm)
referenced to TMS at 0.00 ppm. Proton decoupled carbon chemical
shifts are reported relative to solvent (CDCl3 t at d 77.0 ppm and
CD2Cl2 m at d 55.61 ppm) referenced to TMS at 0.00 ppm. IR spec-
tra were recorded from evaporated solutions on KBr plates on a
Bruker ATR FTIR spectrometer from 625 to 4000 cmꢀ1. UV/vis spec-
tra were recorded as CH2Cl2 solutions on a Thermo Biomate 3S
spectrometer between 300 and 500 nm.
Bipyridines are known to be excellent chelating ligands for a
wide range of transition metals. We have been exploring the chem-
istry of 5-ethynylbipyridine in copper-catalyzed [3+2] cycloaddi-
tion reactions with organic azides as a potentially versatile route
to BFCA’s. In this paper we report on the synthesis and character-
ization of 1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazoles derived
from copper-catalyzed reactions of 5-ethynylbipyridine and three
2.1. 1-Benzyl-4-(5-bipyridyl)-1H-1,2,3-triazole (1)
Copper sulfate pentahydrate (370 mg, 1.48 mmol) and 601 mg
(3.03 mmol) sodium ascorbate are added to a solution of 265 mg
(1.59 mmol) 5-ethynyl-2,20-bipyridine and 318 mg (2.39 mmol)
* Corresponding author.
E-mail address: r.kirss@neu.edu (R.U. Kirss).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.04.019

C. Cote, R.U. Kirss / Inorganica Chimica Acta 363 (2010) 2520–2525
2521
1 R = H
2 R = p-CH3
3 R = m-Br
R
RC6H4CH2N3
N
Cu(II) / NaC6H7O6
aq tBuOH
N
N
N
N
N
N
R
N
[Re(CO)3Br3]2-
MeOH
OC
OC
N
Re
Br
N
N
N
CO
4 R = H
5 R = p-CH3
6 R = m-Br
Scheme 1.
t
benzyl azide in 10 mL 1:1 butanol:water at ambient temperature.
Initially, the mixture is brown but turns green upon stirring. After
3 h the green mixture is poured into 150 mL aqueous ammonia
(9 M) precipitating a solid. Extraction with 3 ꢁ 50 mL CH2Cl2 dis-
solved the solid and yields a yellow organic layer and a blue aque-
ous solution of CuðNH3Þ42þ. The CH2Cl2 extracts were combined
and washed with 2 ꢁ 50 mL 9 M aqueous ammonia, dried over
sodium sulfate, filtered and evaporated to an off-white solid.
Re-crystallization from hot ethyl acetate yielded 260 mg (54%) of
1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazole (1).
M.p. 181–183 °C. Anal. Calc. for C20H17N5: C, 73.38; H, 5.23; N,
21.39. Found: C, 73.49; H, 5.10; N, 21.07%.
1H (300 MHz, CDCl3): d 2.39 s (3H, CH3), 5.56 s (2H, CH2), 7.31 m
(1H), 7.75 s (1H), 7.81 td (J = 1.8, 7.5 Hz, 2H), 8.25 dd (J = 2.1,
8.1 Hz, 2H), 8.42 two overlapping d (J = 8.7 Hz, 4H), 8.68 d (1H),
9.05 m (1H).
13C{1H} (75.4 MHz, CDCl3): d 21.16, 54.17, 119.86, 121.03,
123.5, 128.18, 129.87, 130.15, 131.28, 133.76, 136.90, 138.91,
155.43.
IR (KBr) 641 w, 678 w, 691 w, 747 s, 782 w, 795 w, 830 w, 848
w, 970 m, 1022 w, 1061 w, 1093, 1145 w, 1190 w, 1220 w, 1343 w,
1387 w, 1429 m, 1455 m, 1507 w, 1516 w, 1539 w, 1558 w, 1575
M.p. 197–198 °C. Anal. Calc. for C19H15N5: C, 72.83; H, 4.82; N,
22.35. Found: C, 73.32; H, 4.82; N, 22.48%. Analytical data for 1
are high for % C, but the combination of spectroscopy and conver-
sion of 1 to analytically pure 4 confirm the identity of 1.
1H (300 MHz, CDCl3): d 5.62 s (2H, CH2), 7.31 m (3H), 7.40 m
(3H), 7.79 s (1H), 7.82 t (J = 9.6 Hz, 1H), 8.27 dt (J = 9.6, 1 Hz, 1H),
8.40 d (J = 8.4 Hz, 1H), 8.45 d (J = 7.2 Hz, 1H), 8.68 d (J = 3.9 Hz,
1H), 9.06 m (1H).
m, 1651 w cmꢀ1
UV/vis (CH2Cl2) kmax = 305 (
.
e
= 32,500) nm.
2.3. 1-(m-Bromobenzyl)-4-(5-bipyridyl)-1H-1,2,3-triazole (3)
13C{1H} (75.4 MHz, CDCl3): d 54.87, 119.96, 121.11, 123.74,
126.56, 128.11, 128.92, 129.22, 133.78, 134.34, 136.89, 145.16,
149.18, 150.45, 155.58.
IR (KBr) 677 m, 711 s, 744 s, 794 m, 821 w, 846 w, 859 w, 924 w,
975 m, 1021 w, 1033 m, 1048 w, 1072 w, 1085 w, 1128 w, 1194 m,
1225 m, 1339 w, 1376 w, 1434 m, 1448 m, 1493 w, 1531 w, 1570
w, 1585 w.
Using the procedure described for 1, reaction of 265 mg
(1.59 mmol) 5-ethynyl-2,20-bipyridine, 365 mg (1.72 mmol) m-
bromobenzyl azide, 394 mg, (1.45 mmol) CuSO4ꢂ5H2O and
583 mg (2.94 mmol) sodium ascorbate in 10 mL 1:1 tbutanol:water
at ambient temperature followed by re-crystallization from hot
ethyl acetate yielded 283 mg (47%) of analytically pure 1-m-bro-
mobenzyl-4-(5-bipyridyl)-1H-1,2,3-triazole (3).
M.p. 188–190 °C. Anal. Calc. for C19H15N5Br: C, 58.18; H, 3.60; N,
17.85. Found: C, 58.46; H, 3.66; N, 17.34%.
UV/vis (CH2Cl2) kmax = 305 (e = 22,600) nm.
The procedure above uses a stoichiometric amount of Cu-
SO4ꢂ5H2O. Reactions using catalytic (10–20 mol%) amounts of cop-
per and longer reaction times (1–2 days) produce 1 in lower yields.
Chromatography on silica using 2:1 CH2Cl2:ethyl acetate as the
eluent is required to obtain pure 1. Heating at 60 °C for 3 h failed
to increase yields of 1 in the presence of catalytic amounts of cop-
per sulfate.
1H (300 MHz, CDCl3): d 5.58 s (2H, CH2), 7.28 m (3H), 7.32 m
(1H), 7.50 s (1H), 7.82 s (2H), 8.27 dd (J = 2.1, 8.4 Hz, 1H), 8.41 d
(J = 8.4 Hz, 1H), 8.68 d (J = 4.5 Hz, 1H), 8.70 s (1H) 9.07 s (1H).
IR (KBr) 659 w, 671 w, 679 w, 754 w, 762 w, 775 s, 807 s, 856 w,
994 w, 1046 s, 1071 m, 1082 w, 1155 w, 1199 w, 1258 w, 1297 w,
1342 w, 1358 w, 1426 m, 1465 w, 1572 m, 1598 m cmꢀ1
UV/vis (CH2Cl2) kmax = 248 ( = 26,300) nm.
.
e
2.2. 1-(p-Methylbenzyl)-4-(5-bipyridyl)-1H-1,2,3-triazole (2)
2.4. fac-[1-Benzyl-4-(5-bipyridyl)-1H-1,2,3-triazole]Re(CO)3Br (4)
Using the procedure described for 1, reaction of 261 mg
(1.57 mmol) 5-ethynyl-2,20-bipyridine, 269 mg (2.39 mmol) p-
methylbenzyl azide, 459 mg, (1.84 mmol) CuSO4ꢂ5H2O and
698 mg (3.52 mmol) sodium ascorbate in 10 mL 1:1 tbutanol:water
at ambient temperature followed by re-crystallization from hot
ethyl acetate yielded 138 mg (38%) of analytically pure 1-(p-meth-
ylbenzyl)-4-(5-bipyridyl)-1H-1,2,3-triazole (2).
A mixture of 238 mg (0.31 mmol) [NEt4]2[Re(CO)3Br3] and
51.6 mg (0.17 mmol) 1 in 20 mL methanol was refluxed for 1 h pre-
cipitating a yellow solid. The product was collected by filtering,
washed with 20 mL water and dried. 88.8 mg (80% yield) of fac-
[1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazole]Re(CO)3Br (4) was iso-
lated as a bright yellow powder.

2522
C. Cote, R.U. Kirss / Inorganica Chimica Acta 363 (2010) 2520–2525
M.p. 193–195 °C. Anal. Calc. for C22H15N5O3BrRe: C, 39.83; H,
IR (KBr) 2017 vs (
759 m, 779 m, 793 w, 864 w, 980 w, 1042 w, 1205 w, 1234 w, 1317
w, 1337 w, 1429 w, 1455 w, 1471 w, 1603 cmꢀ1
mCO), 1926 s (mCO), 1892 vs (mCO), 641 w, 678 w,
2.28; N, 10.55. Found: C, 39.47; H, 2.40; N, 10.47%.
1H (300 MHz, CD3COCD3): d 5.76 s (2H, CH2), 7.4 m (5H), 7.78
tm (1H), 8.83 tm (1H), 8.72 m (3H), 8.86 s (1H), 9.13 dm (1H),
9.59 m (1H) (400 MHz, CD2Cl2): d 5.56 s (2H, CH2), 7.29 m (2H),
7.34 m (3H), 7.95 s (1H), 7.99 t (J = 8.0 Hz, 1H), 8.15 m (2H), 8.43
d (J = 8.8 Hz, 1H), 8.95 d (J = 5.2 Hz, 1H), 9.27 s (1H).
.
UV/vis (CH2Cl2) kmax = 266 (e = 14,250), 325 (e = 24,400), 395
(e
= 2375) nm.
2.7. fac-(5-Ethynyl-2,20-bipyridine)Re(CO)3Br (7)
13C{1H} (100.7 MHz, CD2Cl2): d 56.65, 123.96, 125.44, 125.66,
129.10, 130.31, 131.10, 131.37, 132.72, 136.51, 137.42, 141.29,
144.32, 151.88, 155.27, 156.40, 157.46, 191.02, 199.27.
A mixture of 400 mg (0.52 mmol) [NEt4]2[Re(CO)3Br3] and
94 mg (0.57 mmol) 5-ethynylbipyridine in 25 mL methanol was re-
fluxed for 2 h precipitating a tan solid. The crude product was col-
lected by filtering, washed with 20 mL water and dried. The crude
product was chromatographed on silica using a 2:1 mixture of
CH2Cl2:ethyl acetate to elute a single yellow fraction. Evaporation
of the solvent yielded 242 mg (88% yield) of fac-(5-ethynyl-2,20-
bipyridine)Re(CO)3Br (7) as a bright yellow powder.
IR (KBr) 2017 vs (mCO), 1936 sh, s (mCO), 1887 vs (mCO), 640 w, 694
m, 720 w, 757 m, 791 m, 812 m, 858 w, 899 w, 913 w, 979 w, 1039
w, 1071 w, 1115 w, 1144 w, 1172 w, 1190 w, 1206 w, 1231 w, 1313
w, 1393 w, 1435 m, 1454 m, 1470 m, 1495 w, 1540 w, 1558 w,
1602 m cmꢀ1
.
UV/vis (CH2Cl2) kmax = 265 (e = 18,450), 326 (e = 27,200), 398
(
e
= 3450) nm.
M.p. decomposes above 175 °C. Anal. Calc. for C15H8N2O3Re: C,
33.97; H, 1.52; N, 5.28. Found: C, 34.20; H, 1.93; N, 4.92%.
1H (300 MHz, CD3COCD3): d 4.32 s (1H, „CH), 7.82 t (J = 6 Hz,
1H), 8.35 m (2H), 8.74 d (J = 7.8 Hz, 2H), 9.15 s (2H).
2.5. fac-[1-{p-Methylbenzyl}-4-(5-bipyridyl)-1H-1,2,3-
triazole]Re(CO)3Br (5)
IR (KBr) 2020 vs (
w, 1237 w, 1313 w, 1441 w, 1469 m (
mCO), 1894 vs (mCO), 725 w, 751 w, 790 w, 845,
m
CC), 1604 w cmꢀ1
.
A mixture of 235 mg (0.31 mmol) [NEt4]2[Re(CO)3Br3] and
54.3 mg (0.17 mmol) 2 in 20 mL methanol was refluxed for 1 h pre-
cipitating a yellow solid. The product was collected by filtering,
washed with 20 mL water and dried. 80.6 mg (70% yield) of fac-
[1-{p-methylbenzyl}-4-(5-bipyridyl)-1H-1,2,3-triazole]Re(CO)3Br
(5) was isolated as a bright yellow powder.
M.p. >250 °C, decomposes. Anal. Calc. for C23H17N5O3BrRe: C,
40.77; H, 2.53; N, 10.34. Found: C, 40.96; H, 2.42; N, 10.24%.
1H (300 MHz, CD3COCD3): d 2.32 s (3H, CH3), 5.72 s (2H, CH2),
7.22 d (J = 9.1 Hz, 2H), 7.33 d (J = 9.1 Hz, 2H), 7.78 t (J = 6.0 Hz,
1H), 8.32 tm (1H), 8.71 m (3H), 8.82 s (1H), 9.13 d (J = 6.0 Hz,
1H), 9.59 s (1H); (400 MHz, CD2Cl2): d 2.28 s (3H, CH3), 5.51 s
(2H, CH2), 7.17 s (4H), 7.45 t (J = 6.0 Hz, 1H), 7.92 s (1H), 7.99 t
UV/vis (CH2Cl2) kmax = 263 (
= 4400) nm.
e
= 17,900), 309 (
e
= 29,000), 408
(e
2.8. fac-(6-Ethynyl-2,20-bipyridine)Re(CO)3Br (8)
A mixture of 438 mg (0.57 mmol) [NEt4]2[Re(CO)3Br3] and
103 mg (0.62 mmol) 6-ethynylbipyridine in 25 mL methanol was
refluxed for 2 h precipitating a tan solid. The crude product was
collected by filtering, washed with 20 mL water and dried. The
crude product was chromatographed on silica using a 2:1 mixture
of CH2Cl2:ethyl acetate to elute a single yellow fraction. Evapora-
tion of the solvent yielded 278 mg (92% yield) of fac-(6-ethynyl-
2,20-bipyridine)Re(CO)3Br (8) as a bright yellow powder.
(J = 7.2 Hz, 1H), 8.15 m (2H), 8.44
(J = 5.2 Hz, 1H), 9.25 s (1H).
d
(J = 8.0 Hz, 1H), 8.95
d
M.p. decomposes above 180 °C. Anal. Calc. for C15H8N2O3Re: C,
33.97; H, 1.52; N, 5.28. Found: C, 34.15; H, 1.25; N, 5.13%.
1H (300 MHz, CD3COCD3): d 4.76 s (1H, „CH), 7.80 m (1H),
13C{1H} (100.7 MHz, CD2Cl2): d 23.05, 56.49, 123.76, 125.38,
125.60, 129.08, 130.31, 131.99, 132.30, 132.77, 133.29, 133.42,
137.36, 141.27, 144.24, 151.86, 155.26, 156.35.
8.00 m (J = 8.1 Hz, 1H), 8.32 dd (J = 7.8, 8.1 Hz, 2H), 8.71
(J = 8.1 Hz, 2H), 9.19 s (1H).
d
IR (KBr) 2017 vs (
730 w, 758 m, 790 m, 863 w, 979 w, 1042 w, 1234 w, 1315 w, 1346
w, 1442 m, 1456 m, 1470 m, 1603 m cmꢀ1
m
CO), 1926 s (
m
CO), 1889 vs (
m
CO), 640 w, 685 w,
IR (KBr) 2020 vs (
w, 1002 w, 1028 w, 1072 w, 1119 m, 1184 m, 1405 m, 1437 m (mCC
w cmꢀ1
mCO), 1895 vs (mCO), 722 w, 748 w, 787 w, 843
)
.
.
UV/vis (CH2Cl2) kmax = 264 (
e
= 11,500), 326 (
e
= 19,500), 394
UV/vis (CH2Cl2) kmax = 283 (
e
= 10,250), 309 (
e
= 18,000), 402
(e
= 2200) nm.
(e
= 2250) nm.
2.9. fac-(5-Bromo-2,20-bipyridine)Re(CO)3Br (9)
2.6. fac-[1-{m-Bromobenzyl}-4(5-bipyridyl)-1H-1,2,3-
triazole]Re(CO)3Br (6)
A
slurry of 218 mg (0.54 mmol) Re(CO)5Br and 107 mg
(0.52 mmol) 3-bromobipyridine in 25 mL THF was heated to reflux
under nitrogen for 20 h. Solvent was evaporated from the yellow
solution under vacuum yielding 258 mg (86% yield) of fac-(5-bro-
mo-2,20-bipyridine)Re(CO)3Br (9) as a yellow solid.
A mixture of 209 mg (0.27 mmol) [NEt4]2[Re(CO)3Br3] and
99.4 mg (0.26 mmol) 3 in 20 mL methanol was refluxed for 1 h pre-
cipitating a yellow solid. The product was collected by filtering,
washed with 20 mL water and dried. 131 mg (68% yield) of fac-
[1-{m-bromobenzyl}-4(5-bipyridyl)-1H-1,2,3-triazole]Re(CO)3Br
(6) was isolated as a bright yellow powder.
M.p. a sample of 9 remains unchanged upon heating to 250 °C.
Anal. Calc. for C13H7Br2N2O3Re: C, 26.77; H, 1.21; N, 4.80. Found: C,
27.07; H, 1.41; N, 4.97%.
M.p. no changes observed up to 275 °C. Anal. Calc. for
1H (300 MHz, CD3COCD3): d 7.83 t or d (J = 1.2, 7.5 Hz, 1H), 8.35
t of d (J = 1.8, 8.7 Hz, 1H), 8.55 dd (2.4, 12 Hz, 1), 8.74 d (J = 8.7 Hz,
1H), 8.79 d (J = 8.1 Hz, 1H), 9.14 dd (J = 0.6, 5.4 Hz, 1H), 9.21 d
(J = 2.4 Hz, 1H).
C22H14N5O3Br2Re: C, 35.59; H, 1.90; N, 9.43. Found: C, 35.33; H,
1.96; N, 9.30%.
1H (300 MHz, CD3COCD3): d 5.82 s (2H, CH2), 7.38, 7.41 overlap-
ping t (2H), 7.56 dm (1H), 7.66 br s (1H), 8.32 tm (1H), 7.78 tm
(1H), 8.33 tm (1H), 8.73 overlapping m (3H), 9.13 d (J = 5.7 Hz,
1H), 9.58 s (1H); (400 MHz, CD2Cl2): d 5.54 s (2H, CH2), 7.24 m
(2H), 7.42 s (1H), 7.47 t (J = 6.4 Hz, 2H), 7.99 s (1H), 8.01 t
(J = 6.4 Hz, 1H), 8.17 m (2H), 8.48 d (J = 8.4 Hz, 1H), 9.60 d
(J = 4.8 Hz, 1H), 9.28 s (1H).
13C{1H} (75.4 MHz, CD3COCD3): 126.12, 126.79, 129.57, 138.86,
141.38, 141.73, 151.02, 151.66, 155.04, 156.53, 180.78.
IR (KBr) 2015 vs (mCO), 1888 vs (mCO), 642 w, 689 w, 756 m,
788 m, 855 w, 913 w, 1040 w, 1065 w, 1094 w, 1105 w, 1120 w,
1134 w, 1166 w, 1237 w, 1279 w, 1306 w, 1369 w, 1427 w,
1463 w, 1592 cmꢀ1
.

C. Cote, R.U. Kirss / Inorganica Chimica Acta 363 (2010) 2520–2525
2523
UV/vis (CH2Cl2) kmax = 259 (
e
= 27,200), 306 (
e
= 28,375), 406
tion, provided that
a
stoichiometric (or near stoichiometric)
(
e
= 4000) nm.
amount of Cu(I) was used in the reaction. The copper was readily
removed by washing with aqueous ammonia. Compounds 1–3
were characterized by 1H and 13C NMR spectroscopy and gave sat-
isfactory elemental analyzes. Triazoles 1–3 are soluble in dichloro-
methane, chloroform, acetone and ethylacetate but the solubility
of 3 in these polar solvents is significantly lower than for 1–2. As
noted earlier, bipyridine is an excellent chelating ligand, forming
complexes with many transition metals, including Cu(II), the form
of copper used as the catalyst precursor in the reaction [18]. The
coordination of copper to the bipyridine moiety is a likely explana-
tion for the low yields of triazoles observed when catalytic amount
of CuSO4ꢂ5H2O are used in the reaction. A similar observation was
reported in the preparation of roxatanes using Cu-catalyzed ‘‘click”
chemistry [19] although no difficulties were reported in the reac-
tion between 3-ethynyl-1,10-phenanthroline and azidophospho-
nates [20].
2.10. fac-(5-Ethynyl-2,20-bipyridine)Re(CO)3Br (7) from fac-(5-
bromo-2,20-bipyridine)Re(CO)3Br (9)
A mixture of 158 mg (0.27 mmol) 9, 9.1 mg (0.013 mmol,
5 mol%) Pd(PPh3)2Cl2 and 13.2 mg (0.069 mmol) CuI were com-
bined in 5 mL THF under a nitrogen atmosphere. A solution of
3 mL triethylamine containing 200 lL trimethylsilylacetylene was
added leading to a color change from yellow to red. The mixture
was heated at 60 °C for 3 h and then stirred at ambient tempera-
ture overnight. The mixture was filtered to remove a dark solid
and the filtrate evaporated to a yellow-brown solid. Chromatogra-
phy of the solid on silica using a 1:2 (v/v) mixture of ethyl acetate
to dichloromethane slowly eluted an orange yellow band. Evapora-
tion of the solvent followed by washing with hexane (5 mL)
1 R = H
2 R = p-CH 3
3 R = m-Br
RC6H4CH2N3
R
N
Cu(II) / NaC 6H7O6
aq tBuOH
N
ð1Þ
N
N
N
N
N
yielded 23 mg (14%) of yellow-orange solid fac-[5-(trimethylsilyle-
thynyl)-2,20-bipyridine]Re(CO)3Br (10). The 1H NMR spectrum of
10 was consistent with the formulation fac-[5-(trimethylsilylethy-
nyl)-2,20-bipyridine]Re(CO)3Br but further purification and charac-
terization was not attempted. Compound 10 was immediately
used in the next step.
Triazoles 1–3 are assigned as the 1, 4-isomers by analogy to the
literature of Cu-catalyzed [3+2] cycloaddition chemistry [21]. Ef-
forts at preparing the 1, 5-isomer using catalytic amounts of
*
Cp Ru(PPh3)2Cl [22] were unsuccessful. No triazole products were
isolated from the black reaction mixture. When followed by 1H
NMR in C6D6 solution, no reaction was observed between 5-ethy-
nyl-2,20-bipyridine and benzyl azide in the presence of 5 mol%
1H NMR (300 MHz, CD3COCD3): d 0.30 s (9H, Me3Si), 7.81 td
(J = 1.2, 5.7 Hz, 1H), 8.33 d (J = 9.3 Hz, 2H), 8.70 t (J = 5.7 Hz, 2H),
9.12 d (J = 14.1, 3.9 Hz, 2H).
*
Cp Ru(PPh3)2Cl. Substitution of PPh3 by the 5-ethynyl-2,20-bipyri-
A 22 mg (0.037 mmol) sample of 10 was dissolved in 20 mL of
1:1 (v/v) THF:methanol to give a yellow-orange solution. Addition
of 46.3 mg (0.80 mmol) KF did not lead to an observable color
change after 3 h at ambient temperature. Evaporation of the sol-
vent and chromatography on silica using 1:2 EtOAc:CH2Cl2 eluted
a yellow band which upon evaporation, yielded 12 mg (62%) of 7.
dine substrate may be responsible for the lack of reactivity in this
case.
Reactions between triazoles 1–3 and [NEt4]2[Re(CO)3Br3]
yielded the corresponding Re(CO)3Br coordination compounds 4–
6 in good yield (70–80%, Eq. (2)). Compounds 4–6 precipitated
out of methanol and required no further purification beyond wash-
ing with water to remove any alkyl ammonium salts. The rhenium
compounds 4–6 are slightly soluble in acetone and DMSO but
nearly insoluble in halocarbons or other polar solvents. Like 1–3,
compounds 4–6 gave satisfactory elemental analyzes and were
characterized by 1H NMR spectroscopy. The reactions appear to
be very rapid in refluxing methanol with a characteristic color
change from the tan hues of the starting materials to the bright yel-
low color of the rhenium carbonyl complexes noticeable even at
room temperature in less than 30 s after mixing. The reactions
were continued for 1–2 h, however, to ensure complete consump-
tion of the starting materials. The observation of three strong m(CO)
stretches between 1875 and 2025 cmꢀ1 in the IR spectra of 4–6 are
consistent with a fac-geometry for the carbonyl ligands and reflect
the asymmetry of the triazole-substituted bipyridine [23] com-
pared to the IR spectrum of fac-(5-bromobipyridine)Re(CO)3Br
(9). The IR spectra for 4–6 and 9 are similar to that for fac-(bipyr-
idine)Re(CO)3Br [24]. UV/vis spectra of 4–9 show a metal-to-ligand
charge transfer band around 400 nm similar to that observed for
fac-(bipyridine)Re(CO)3Br [25].
2.11. fac-[1-Benzyl-4-(5-bipyridyl)-1H-1,2,3-triazole]Re(CO)3Br (4)
from fac-(5-ethynyl-2,20-bipyridine)Re(CO)3Br (7)
A mixture of 48 mg (0.092 mmol) 7, 28 mg (0.21 mmol) benzyl
azide, 27 mg (0.11 mmol) CuSO4ꢂ5 H2O, and 38 mg (0.19 mmol) so-
t
dium ascorbate were reacted in 1:1 BuOH:water (5 mL) at 90 °C
for 3 h and then cooled to ambient temperature overnight. The yel-
low-green slurry was poured into 25 mL concentrated ammonia
and extracted with 5 ꢁ 15 mL CH2Cl2. After work-up as described
for 1, 18 mg of a mixture containing 50%, 4 and 50%, 7 was isolated
after crystallization from ethylacetate:hexane and comparison of
the 1H NMR spectrum with authentic samples.
3. Results and discussion
The synthesis of 1-benzyl-4-(5-bipyridyl)-1H-1,2,3-triazoles
(1–3) proceeded in good yield (38–54%, Eq. (1)) after re-crystalliza-

2524
C. Cote, R.U. Kirss / Inorganica Chimica Acta 363 (2010) 2520–2525
R
R
N
N
[Re(CO) 3Br3 ]2-
MeOH
OC
OC
N
N
Re
ð2Þ
Br
N
N
N
N
N
CO
N
1 R = H
2 R = p-CH 3
3 R = m-Br
4 R = H
5 R = p-CH 3
6 R = m-Br
We were also curious about whether or not click chemistry was
possible using pre-formed Re(CO)3Br complexes of 5-ethynyl-2,20-
bipyridine. While such an approach is not useful for the prepara-
tion of BFCA’s for imaging with short half-life radioisotopes, the
reactions of (5-ethynyl-2,20-bipyridine)Re(CO)3Br with benzyl
azide acts as a test of the electronic effect of an electron withdraw-
ing Re(CO)3Br group on the ‘‘click” reaction. Prior coordination of
the Re(CO)3Br group also ties up the nitrogen lone pairs in 2,20-
bipyridine that proved to be problematic in the synthesis of 1–3.
Both 5-ethynyl (7) and 6-ethynyl-2,20-bipyridine Re(CO)3Br (8)
were prepared in nearly quantitative yield (>90%, Eq. (3)) by the
Reaction between 7 and benzyl azide in the presence of cata-
lytic CuSO4ꢂH2O (30 mol%) and sodium ascorbate at ambient tem-
perature for 7 days failed to yield measurable amounts of 4.
Increasing the reaction time and temperature alone proved equally
ineffectual. Increasing the catalyst concentration and heating at
90 °C for 3 h yielded a 1:1 mixture of 4 and unreacted 7 (Eq. (4)).
While it is possible that further improvements to yield may be pos-
sible, it is clear that the best route to complexes such as 4–6 lies
with introduction of the triazole functionality before coordination
to Re(CO)3Br.
N
C6H5CH2N3
N
ð4Þ
N
OC
OC
Cu(II) / NaC H7O6
OC
OC
N
6
Re
aq tBuOH
Re
Br
Br
N
N
N
CO
CO
4
7
same procedure used to synthesize 4–6. In fact, 7 could also be pre-
pared by a palladium-catalyzed Sonogashira reaction of 5-bromo-
2,20-bipyridineRe(CO)3Br with trimethylsilylacetylene followed by
removal of the TMS group [15]. Yields of 7 by this route (9%) are
considerably lower than from reactions between 5-ethynyl-2,20-
bipyridine and [NEt4]2[Re(CO)3Br3] (88%) although no effort was
expended at optimization of the former.
4. Conclusions
We have successfully demonstrated the synthesis of a short ser-
ies of 1-benzyl-4-(5-bipyridyl) -1H-1,2,3-triazoles starting from 5-
ethynyl-2,20-bipyridine and simple substituted benzyl azides as
well as the preparation of the corresponding Re(CO)3Br complexes.
The complexation of 1–3 to rhenium is rapid and proceeds in high
TMS
1.
[Re(CO)3Br3]2-
Pd(PPh3)2Cl2
NEt3/THF
N
N
N
MeOH
N
ð3Þ
OC
OC
N
OC
OC
2. KF/MeOH
Re
Re
Br
N
Br
Br
CO
CO
7

C. Cote, R.U. Kirss / Inorganica Chimica Acta 363 (2010) 2520–2525
2525
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in the preparation of 2, Professor Robert Hanson for helpful discus-
sions and Northeastern University for support through the EN-
HANCE program.
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