E. Oheix, N. Spencer, L. A. Gethings, A. F. A. Peacock
ARTICLE
in the freezer overnight. A white solid precipitate was collected by phine)palladium(0) (0.38 g, 0.33 mmol) was refluxed in degassed tolu-
filtration, air-dried, and recrystallized from CHCl , to afford white ene (40 mL) for 5 days under a nitrogen atmosphere. Extra tetrakis(tri-
crystals (0.219 g, 30%). H NMR (300 MHz, CDCl ): 8.69 (d, phenylphosphine)palladium(0) (0.38 mg, 0.33 mmol) was added and
H6–H4 = 2.1 Hz, 2 H, H ), 8.41 (d, JH3–H4 = 8.2 Hz, 2 H, H ), 7.86 the reaction was refluxed for a further day under a nitrogen atmo-
3
1
3
3
6
3
3
J
3
3
4
7
13
(
dd, JH4–H6 = 2.3, JH4–H3 = 8.2 Hz, 2 H, H ), 4.54 (s, 4 H, H ).
NMR H decoupled (100 MHz, CDCl ): 155.4 (C ), 149.4 (C ), 137.9
3
C
sphere. The crude mixture was then concentrated in vacuo, and dichlo-
romethane (50 mL) and 6 m hydrochloric acid (10 mL) added to form
a dark brown slurry. The aqueous layer was washed with dichlorometh-
ane (2 ϫ 50 mL) and the combined organic layers were washed with
6 m hydrochloric acid (3 ϫ 10 mL). The combined aqueous layers
were filtered and cooled in ice. Ammonia was slowly added until a
light brown solid precipitated out. The resulting solid was filtered, air
1
2
6
4
5
3
7
(
C ), 134.1 (C ), 121.4 (C ), 29.6 (C ). HRES-TOF (CH
2 2
Cl ): calcu-
lated mass for C12 Br Na = 362.9108; measured = 362.9126
H
10
N
2
2
+
([M + Na] , 100%).
Synthesis of 2-Bromo-6-methylpyridine
dried, redissolved in dichloromethane, dried with Na
trated in vacuo. The crude product was purified over chromatography
8%) was cooled to –20 °C in an ethanol bath. Bromine (14.4 mL, column (Al , hexane/DCM gradient) to afford the pure 6,6’’-di-
80 mmol) was added dropwise, and the suspension was stirred for methyl-2,2’:6’,2’’-terpyridine as a white solid (0.63 g, 41%). H NMR
2 4
SO , and concen-
2
4
2
9
2
-Bromopicoline (10.8 g, 115 mmol) in hydrobromic acid (40 mL,
2 3
O
1
3
3
0 min at –20 °C. An aqueous solution of NaNO
68 mmol) was added dropwise, and the solution was allowed to warm
2
3
(30 mL, 8.9 m, (300 MHz, CDCl ): 8.46 (d, JH3–H4 = 7.8 Hz, 2 H, H ), 8.41 (d,
3
3a
3
4
J
H3a–H4a = 7.8 Hz, 2 H, H ), 7.93 (t, JH4–H3 = 7.8 Hz, 1 H, H ), 7.73
3
4a
3
to room temperature over 2 hours with stirring. The mixture was re-
(t, 3JH4a–H3a
H5a–H4a
~ JH4a–H5a = 7.7 Hz, 2 H, H ), 7.19 (d, J =
5
a
7
13
1
cooled to –20 °C, and a cool NaOH aqueous solution (110 mL, 16.5 7.6 Hz, 2 H, H ), 2.65 (s, 6 H, H ). C NMR H decoupled
6
a
2/2a
2/2a
M, 1.81 mol) added slowly, while maintaining the temperature below
10 °C. The mixture was allowed to warm to room temperature over
3
(100 MHz, CDCl ): 158.0 (C ), 155.9 (C ), 155.8 (C ), 137.8
4
4a
5a
3
3a
7
–
(C ), 137.1 (C ), 123.3 (C ), 121.0 (C ), 118.3 (C ), 24.8 (C );
HRES-TOF (CH Cl ): calculated mass for C17 Na = 284.1164;
measured = 284.1152 : ES-TOF m/z = 284.0 [M + Na] (100%).
the course of an more hour with continuous stirring. The mixture was
then extracted with ethyl acetate and the organic layer dried with
2
2
15 3
H N
+
Na
2 4
SO , filtered, and concentrated in vacuo. The dark oil was then
purified by Kugelrohr distillation to yield a colourless oil (9.906 g,
0%). 1H NMR (300 MHz, CDCl
): 7.43 (t, 3
3
Synthesis of 6,6’’-Dibromomethyl-2,2’:6’,2’’-terpyridine
5
3
J
H4–H5
=
J
H4–H3
=
4
3
5
7
J
.7 Hz, 1 H, H ), 7.29 (d,
J
H5–H4 = 7.9 Hz, 1 H, H ), 7.10 (d,
H3–H4 = 7.4, 1 H, H ), 2.54 (s, 3 H, H ). C NMR H decoupled
A solution of 6,6’-dimethyl-2,2’:6’,2’’-terpyridine (0.44 g, 1.7 mmol),
N-bromosuccinimide (0.77 g, 4.3 mmol) and azobisisobutyronitrile
3
3
7
13
1
6
2
4
5
3
(100 MHz, CDCl ): 160.2 (C ), 141.5 (C ), 138.7 (C ), 125.2 (C ),
(
5
(
10 mg, 0.06 mmol) in dichloromethane (30 mL) was refluxed using a
00 W halogen lamp. Progress of the reaction was monitored by TLC
SiO , eluent: CH Cl /CH OH (9/1)). After 15 hours, further N-bro-
mosuccinimide (0.3 g, 1.7 mmol) was added and the reaction refluxed
for a further 17 hours. The mixture was extracted with 0.1 m NaHCO
(5 ϫ 50 mL), the organic layers dried with Na SO and concentrated
3
7
122.2 (C ), 24.3 (C ). HRES-TOF (CH
2
Cl
2
): calculated exact mass
BrN = 170.9684; measured = 170.9686: ES-TOF m/z =
7
9
for C
6
H
6
.+
+
+
2
2
2
3
2 3
171.0 ([M ], 50%), 92.0 ([M-Br] , 100%), 65.0 ([M-C H Br] , 75%).
3
Synthesis of 2-Tributylstannyl-6-methylpyridine
2
4
3 3
in vacuo. Addition of a 50/50 mix CHCl /CH OH (15 mL) and storage
at –20 °C overnight resulted in the formation of a white precipitate.
This was collected by filtration, air-dried, and recrystallized from
A solution of 2-bromo-6-methylpyridine (4.63 g, 27 mmol) in dry THF
(
(
20 mL) was cooled to –60 °C, 27 mL of n-butyllithium in hexane
1.1 m, 30.1 mmol) added dropwise, and the solution was stirred for 2
1
CHCl
CDCl
3
to afford white crystals (0.41 g, 58%). H NMR (300 MHz,
hours at 0 °C. Tributyltin chloride (8.9 mL, 32.8 mmol) was slowly
added and the solution allowed to return to room temperature over 20
minutes with continuous stirring. Water (30 mL) was added into the
reaction mixture, and phases were separated. The organic phase was
washed with water (3 ϫ 30 mL), and the combined aqueous layers
washed with ethyl ether (4 ϫ 30 mL). The combined organic phases
were dried with Na SO , filtered, and concentrated in vacuo to afford
2 4
a black oil (9.534 g, 92%). The crude product was determined to be
ca. 95% pure by GC analysis and so used directly in the following
3
3
3
3
): 8.53 (d,
J
H3–H4 = 7.8 Hz, 2 H, H ), 8.52 (d,
H4–H3 = 7.8 Hz, 1 H, H ), 7.86 (t,
H4a–H3a ~ JH4a–H5a = 7.8 Hz, 2 H, H ), 7.50 (d, JH5a–H4a = 7.7 Hz,
J
H3a–H4a
=
3
a
3
4
7
J
.8 Hz, 2 H, H ), 7.96 (t,
J
3
3
4a
3
5
a
7
13
1
2
H, H ), 4.66 (s, 4 H, H ). C NMR H decoupled (100 MHz,
2
/2a
2/2a
6a
4
3
CDCl ): 156.4 (C ), 156.1 (C ), 155.1 (C ), 138.0 (C ), 137.0
4
a
5a
3a
3
7
(
C ), 123.6 (C ), 121.6 (C ), 120.4 (C ), 34.3 (C ); HRES-TOF
CH Cl ): calculated exact mass for C17H N Br BrNa = 441.9353;
2 2 13 3
7
9
81
(
+
measured = 441.9355 ([M + Na] ).
1
3
3
synthesis. H NMR (300 MHz, CDCl
3
): 7.36 (t, JH4–H5 = JH4–H3
=
=
4
3
5
3
7
7
.5 Hz, 1 H ), 7.17 (d, JH4–H5 = 7.3 Hz, 1 H, H ), 6.96 (d, JH4–H3
.9, 1 H, H ), 2.54 (s, 3 H ), 1.56 (m, 6 H, H ), 1.33 (m, 6 H, H ),
.09 (m, 6 H, H ), 0.88 (t, JH11–H10 = 7.2, 9 H, H ). C NMR H
Synthesis of bipy-GS : 5,5’-Bis(methyl-S-glutathionyl)-2,2’-
2
3
7
9
10
bipyridine
8
3
11 13
1
1
6
2
4
decoupled (100 MHz, CDCl
3
): 173.2 (C ), 158.7 (C ), 133.3 (C ), A solution of l-glutathione (30.3 mM, 5 mL, 0.152 mmol) in 100 mM
5
3
9
10
7
11
1
1
C
29.5 (C ), 121.6 (C ), 29.2 (C ), 27.5 (C ), 25.1 (C ), 13.8 (C ),
Tris.HCl buffer pH 8.0 was added to a solution of 5,5’-bis(bromome-
thyl)-2,2’-bipyridine (15.3 mM, 76.6 μmol, 5 mL) in acetonitrile. The
384.1715: ES-TOF resulting suspension was degassed with N2(g) for 10 minutes and then
19] , 54%), 211.9 stirred for 11 hours at room temperature. The solvent was evaporated
4 9 8
m/z = 326.0 ([M-C H ] , 52%), 268.0 ([M-C H
8
0.0 (C ). HRES-TOF (CH
2
Cl
2
): calculated exact mass for
H
33
N
120Sn
=
384.1713; measured
=
18
+
+
+
+
(
(
[M-C12
[M-C18
H
H
26] , 100%), 177.0 ([M-C14
H
24] , 14%), 120.9
in vacuo at 50 °C to yield a pink gel. Deionised water (ca. 5 mL) and
few drops of HCl (35%) were added to the gel resulting in complete
solubilisation. The pH was neutralised on addition of NaOH (1 m)
solution. The product was purified by preparative RP-HPLC (C18 Phe-
nomenex, monitoring absorbance at 210 and 290 nm) using 0 to 15%
+
+
32] , 37%), 93.1 ([M-C12
H26Sn] , 25%).
Synthesis of 6,6’’-Dimethyl-2,2’:6’,2’’-terpyridine
A solution of 2,6-dibromopyridine (1.39 g, 5.9 mmol), 2-tributylstan- gradient acetonitrile in water (containing 0.05% TFA) over 30 min.
nyl-6-methyl-pyridine (5.02 g, 13.1 mmol) and tetrakis(triphenylphos- The solvent was evaporated in vacuo to yield pure 5,5’-bis(methyl-S-
1
380 www.zaac.wiley-vch.de
© 2013 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Z. Anorg. Allg. Chem. 2013, 1370–1383