Disulfide-functionalized 3-, 4-, 5-, and 6-substituted 2,2'-bipyridines and their ruthenium complexes

Full text of DOI:10.1021/jo9814795

J . Org. Chem. 1999, 64, 1015-1021
1015
al. to the synthesis of ethyl 2,2′-bipyridine-5-carboxylate.5
It involved the palladium-catalyzed coupling of a pyridyl-
trimethylstannane with a pyridyl halide. We have found
this procedure to be well suited for making all of our
unsymmetrically substituted 2,2′-bipyridines. This paper
describes the first syntheses of the ruthenium complexes
of disulfide-functionalized 2,2′-bipyridines.
Disu lfid e-F u n ction a lized 3-, 4-, 5-, a n d
6-Su bstitu ted 2,2′-Bip yr id in es a n d Th eir
Ru th en iu m Com p lexes
Charles A. Panetta,*,† Hephzibah J ayasheela Kumpaty,‡
Norman E. Heimer,§ Montray C. Leavy,† and
C. L. Hussey†
Methyl 6-chloropyridine-2-carboxylate6 was prepared
from the commercial 6-hydroxypyridine-2-carboxylic acid
and was then coupled with trimethylstannylpyridine7 to
afford the known methyl 2,2′-bipyridine-6-carboxylate
(1a ).8,9 The ester, 1a , was reduced to the hydroxymeth-
ylbipyridine (2a ) which was then esterified with 3,3′-
dithiodipropanoic acid to yield the bipyridine disulfide
ester (3a ). The methyl 2-chloropyridine-5- and 4-carboxy-
lates were similarly treated to afford 3b and 3c, respec-
tively. The overall yields of 3a , b, and c from trimeth-
ylstannylpyridine and the methyl chloropyridine-
carboxylates were, respectively, 18, 23, and 7% (Scheme
1).
Four examples of the 5-substituted 2,2′-bipyridine
disulfides (3b, 5b n ) 2, 5b n ) 10, 8) were prepared.
They differed mainly in the length of the side chains
(from five to twelve atoms) which incorporated amide or
ester groups. As with all of the bipyridines, these were
synthesized from the appropriate methyl chloropyridine-
carboxylates and trimethylstannylpyridines. Methyl 2,2′-
bipyridine-5-carboxylate (1b) was prepared from com-
mercially available 2-chloropyridinecarboxylic acid (6-
chloronicotinic acid) following the procedure that Ghadiri5
reported for the ethyl ester, except that the reaction
mixture was refluxed for 6-7 h in m-xylene instead of
24 h in THF. This modification increased the yield of the
ester from 45 to 84%. After saponification of the bipyridyl
ester, 1b, the resultant 2,2′-bipyridine-5-carboxylic acid
(4b) was converted to the amide of cystamine, 5b (n )
2), under Schotten-Baumann conditions (see Scheme 2).
The di(10-aminodecyl) disulfide (n ) 10) was synthesized
by a three-step procedure10 which began with the prepa-
ration of N-(10-bromodecyl)phthalimide. Treatment of the
latter with benzyltriethylammonium tetrathiomolyb-
date11 converted it to the di(10-phthalimidyldecyl) dis-
ulfide which was deprotected with hydrazine to afford
the amino disulfide (n ) 10). This was condensed with
the 2,2′-bipyridine-5-carboxylic acid chloride to give the
long-chain bipyridyl disulfide, 5b (n ) 10). The methyl
2-chloropyridine-4-carboxylate, needed for the syntheses
of the 4-substituted 2,2′-bipyridines (1c), was prepared
by a route that included the chlorination of pyridine
N-oxide 4-carboxylic acid.12,13 Methyl 2-chloropyridine-
3-carboxylate was made from the commercial carboxylic
acid and then condensed with 2-trimethylstannylpyridine
The Department of Chemistry, The University of Mississippi,
University, Mississippi 38677, The Department of
Chemistry, The University of Wisconsin-Whitewater,
Whitewater, Wisconsin 53190, and The Department of
Chemistry, U.S. Air Force Academy,
USAFA, Colorado 80840-6230
Received J uly 27, 1998
The self-assembly of ruthenium complexes of bipyri-
dine thiols was studied by Obeng and Bard in 1991.1 They
used a complex containing 4-methyl-4′-(dodecyl-1-thiol)-
2,2′-bipyridine deposited on gold and indium-doped tin
oxide surfaces. More recently, Yamada and co-workers2
used a sulfide-functionalized chain also attached to the
4-position of a ruthenium-complexed 2,2′-bipyridine.
This paper reports the synthesis of nine 2,2′-bipy-
ridines that were substituted on the 3-, 4-, 5-, and
6-positions with chains containing disulfide functional
groups. The chains varied from four to twelve atoms in
length between the disulfide and the bipyridine nucleus
and incorporated ester or amide linkages. The latter
moiety has been known to stabilize self-assembled mono-
layers (SAMs) through interchain hydrogen bonding.3 All
of the 2,2′-bipyridines were unsymmetrically substituted.
Six were converted to their redox active ruthenium(II)
complexes which were submitted to electrochemical
evaluation on antimony-doped tin oxide (ATO) electrodes.
The work described below resulted in the following
conclusions regarding the effects of some key features of
molecular design on the electrochemical properties of the
modified electrodes. First, the surface coverages for these
bipyridine disulfide complexes were found to be compa-
rable to those measured for bipyridine thiols by Obeng
and Bard.1 The best coverages were observed with those
complexes with the longest carbon chains between the
bipyridine nucleus and the disulfide group. However, the
complexes with short chains had lower oxidation poten-
tials. Last, for complexes immobilized on gold electrodes,
the highest electron-transfer rates were obtained with
the 4-substituted bipyridines. In short, SAMs prepared
from the disulfide derivatives of ruthenium bipyridine
complexes have few advantages or disadvantages com-
pared to those of the corresponding thiols.
The unsymmetrically substituted 2,2′-bipyridines pre-
pared in this work were synthesized using modifications
of a method that was first used by Bailey for the
preparation of biaryls4 and later applied by Ghadiri et
(5) Ghadiri, M. R.; Soares, C.; C., C. J . Am. Chem. Soc. 1992, 114,
825.
(6) Fischer, E.; Hess, K.; Stahlschmidt, A. Chem. Ber. 1912, 45, 2456.
(7) Yamamoto, Y.; Yanagi, A. Chem. Pharm. Bull. 1982, 30, 1731.
(8) Norrby, T.; Borje, A.; Zhang, L.; Akermark, B. Acta Chem. Scand.
1998, 52, 77-85.
(9) Potts, K. T. Bull. Soc. Chim. Belg. 1990, 99, 741.
(10) Dirscherl, v. W.; Weingarten, F. W. Ann. 1951, 574, 131.
(11) Ramesha, A. R.; Chandrasekaran, S. Synth. Commun. 1992,
22, 3277.
(12) Brown, E. V.; Moser, R. J . J . Heterocycl. Chem. 1971, 8, 189.
(13) Seydel, J . K.; Schaper, K.-J .; Wempe, E.; Cordes, H. P. J . Med.
Chem. 1976, 19, 483.
† The University of Mississippi.
‡ The University of Wisconsin-Whitewater.
§ U.S. Air Force Academy.
(1) Obeng, S. Y.; Bard, A. J . Langmuir 1991, 7, 195.
(2) Yamada, S.; Kohrogi, H.; Matsuo, T. Chem. Lett. 1995, 639.
(3) Tam-Chang, S. W.; Biebuyck, H. A.; Whitesides, M. G.; J eon, N.
Langmuir 1995, 11, 4371.
(4) Bailey, T. R. Tetrahedron Lett. 1986, 27, 4407.
10.1021/jo9814795 CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/20/1999

1016 J . Org. Chem., Vol. 64, No. 3, 1999
Notes
Sch em e 1
Sch em e 2
Sch em e 3
Ta ble 1. Th e Syn th eses of Meth yl 2,2′-Bip yr id in e-6-, 5-, 4-, a n d 3-ca r boxyla tes (1a -d ) fr om Tr im eth ylsta n n ylp yr id in e
a n d Meth yl Ch lor op yr id in eca r boxyla tes
product
no.a
symmetrical
byproduct yield, %
product
yield, %
IR,
solvent
temp, °C
heating, h
mp, °C
lit. mp, °C
ν cm-1
1a
1b
1c
1cb
1c
1c
1c
1d
DMF
130
135
135
120
100
68
12
7
0
0
0
0
2
8
7
0
61
84
52
40
46
21
18
86
77-79
108-110
79-80
83.5-84.0c
1722
1722
1731
m-xylene
m-xylene
m-xylene
dioxane
THF
d
d
12
12
20
36
24
16
THF
dioxane
68
100
55-56
53-55e
1722
a
b
d
Five mole % of (PPh3)2PdCl2 used. Three mole % of (PPh3)2PdCl2 used. c Reference 8. Only the ethyl esters are known.14 e Reference
15.
Ta ble 2. Th e Syn th eses of 6-, 5-, a n d 4-(Hyd r oxym eth yl)-2,2′-bip yr id in es (2a , b, a n d c) fr om Meth yl
2,2′-Bip yr id in eca r boxyla tes (1a , b, a n d c) a n d LiAlH4
product yield,
no.
%
IR (film), ν cm-1
1H NMR (CDCl3), δ
2a
86
3424 (br), 3046, 2930, 1582, 1430 8.57 (d, 1H), 8.32-8.21 (m, 2H), 8.05 (d, 1H), 7.72 (m, 2H), 7.21 (m, 1H),
4.60 (s, 2H)
2ba
2c
92
58
3619, 2941, 1590, 1555, 1461,
1017, 926
8.64 (dq, 1H), 8.56 (d, 1H), 8.32-8.26 (m, 2H), 7.84-7.7 (m, 2H), 7.3 (s, 1H),
4.72 (2H)
3323, 3022, 2970, 1587, 1559,
1403, 1226, 1049
8.53 (br d, 1H), 8.45 (d, 1H), 8.19 (m, 2H), 7.7 (br t, 1H), 7.2 (m, 2H), 4.65 (s, 2H)
a
Reference 16.
in dioxane to afford 1d . The overall yields of 5b, c, and
d (n ) 2) from the methyl chloropyridinecarboxylates
were, respectively, 40, 29, and 29%. For products 5b and
c (n ) 10), the overall yields were 43 and 30%, respec-
tively.
important precursors of the 2,2′-bipyridine disulfides.
Table 1 summarizes the experimental results of this
synthetic step; further results are given in Tables 2-6.
Six of the 2,2′-bipyridine disulfides were converted to
their ruthenium complexes by treating each of them with
cis-dichlorobis(2,2′-bipyridine)ruthenium(II) dihydrate in
ethanol solution (3a f 9; 5b f 10, 11; 5c f 12, 13; 5d
f 14). The complexes were precipitated as hexafluoro-
phosphate salts, purified on neutral alumina, and re-
crystallized from acetone/ether or acetonitrile/ether. The
yields ranged from 65 to 80%. The UV-vis spectra
The 5-(hydroxymethyl)-2,2′-bipyridine (2b) was also
used to prepare 2,2′-bipyridine disulfide with a five-atom
amide side chain (8) (Scheme 3).
The methods of Bailey4 and Ghadiri5 were found to be
well-suited to the preparations of the methyl 2,2′-bipy-
ridine-6-, 5-, 4-, and 3-carboxylates (1a -d ) which are

Notes
J . Org. Chem., Vol. 64, No. 3, 1999 1017
Ta ble 3. Th e Syn th eses of Di[(2,2′-bip yr id in -6-, 5-, a n d 4-yl)m eth yl] 3,3′-Dith iod ip r op a n oa tes (3a , b, a n d c) fr om 6-, 5-,
a n d 4-(Hyd r oxym eth yl)-2,2′-bip yr id in es (2a , b, a n d c) a n d 3,3-Dith iod ip r op a n oic Acid
Anal. Calcd for C28H26N4O4S2 (546.7):
product
no.
yield,
%
C, 61.52; H, 4.79; N, 10.25; S, 11.73.
Found:
mp, °C
IR (film), ν cm-1
1H NMR (CDCl3), δ
3a
3b
3c
101-102
34
30
23
2925, 1738, 1582,
1430, 1270, 744
8.66 (dd, 1H), 8.43 (d, 1H), 8.31 (d, 1H), 7.83
(m, 2H), 7.38-7.26 (m, 2H), 5.34 (s,
C, 61.40; H, 4.82; N, 10.32; S, 11.64
2H), 3.01 (t, 2H), 2.89 (t, 2H).
101-102
1738, 1590, 1558,
1462, 1273, 1236,
882
2990, 1740, 1659,
1597, 1462, 1224
8.7 (m, 2H), 8.4 (m, 2H), 7.85 (m, 2H), 7.34
(m, 1H), 5.2 (s, 2H), 2.95 (t, 2H), 2.84 (t, 2H)
C, 61.26; H, 4.82; N, 9.90; S, 11.49
oil
8.67 (d, 2H), 8.36 (m, 2H), 7.83 (ddd, 1H), 7.25 C, 61.42; H, 4.82; N, 10.25; S, 11.73
(m, 2H), 5.2 (s, 2H), 2.97 (t, 2H), 2.88 (t, 2H)
Ta ble 4. Th e Syn th eses of 2,2′-Bip yr id in e-5-, 4-, a n d 3-ca r boxylic Acid s (4b, c, a n d d ) fr om th e Sa p on ifica tion of th e
Meth yl 2,2′-Bip yr id in eca r boxyla tes (1b, c, a n d d )
product
no.
yield,
%
mp, °C
IR (film), ν cm-1
3448-3096 (br), 1678, 1654, 1534, 1458, 1398, (in DMSO) 9.2 (d, 1H), 8.78 (dd, 1H), 8.4-8.5 (m, 3H),
1016, 749 8.0 (ddd, 1H), 7.5 (m, 1H)
1H NMR (CDCl3), δ
4b
196-198
80
89
77
4c
4d
233-234
108-109
3448-3000 (br), 2900, 1670, 1654, 1534, 1458, (in DMSO) 9.0 (d, 1H), 8.85 (m, 2H), 8.64 (d, 1H),
1398, 1314, 1016, 749
3440 (br), 1680, 1552, 1480
8.3 (t, 1H), 8.0 (d, 1H), 7.7 (m, 1H)
8.83 (m, 2H), 8.79 (dd, 1H), 8.60 (d, 1H), 8.12 (ddd, 1H),
7.61 (m, 1H), 7.52 (dd, 1H)
Ta ble 5. Th e Syn th eses of Di[2-(2,2′-bip yr id in e-5-, 4-, a n d 3-ca r boxa m id o)eth yl] Disu lfid es (5b, c, a n d d , n ) 2) fr om
2,2′-Bip yr id in e-5-, 4-, or 3-ca r boxylic Acid (4b, c, a n d d ) a n d Cysta m in e Dih yd r och lor id e
Anal. Calcd for C26H24N6O2S2
product
no.
yield,
%
IR (CHCl3),
(516.7): C, 60.04; H, 4.68; N,
16.26; S, 12.42
mp, °C
ν cm-1
1H NMR (CDCl3), δ
5b n ) 2 203-204
5c n ) 2 178-180
5d n ) 2 120-123
59
63
43
3442, 2927, 1672,
1585, 1552, 1518,
1459, 1268
9.15 (d, 1H, J ) 1.7 Hz), 8.68 (ddd, 1H, J ) 0.83,
1.8, 5.0 Hz), 8.46 (m, 2H), 8.29 (dd, 1H, J ) 1.7,
8.27 Hz), 7.84 (ddd, 1H, J ) 1.8, 7.8, 7.8 Hz),
7.35 (m, 2H), 3.86 (q, 2H), 3.05 (t, 2H)
9.1 (d, 1H), 8.97 (dd, 1H), 8.72 (d, 1H), 8.44 (m, 1H),
8.35 (dd, 1H), 8.0 (d, 1H), 7.5 (m, 1H), 6.8 (t, 1H),
3.85 (q, 2H), 3.0 (t, 2H)
semihydrate; Calcd: C, 59.42;
H, 4.76; N, 16.26; S, 12.19.
Found: C, 59.43; H, 4.55;
N, 16.04; S, 12.17
hydrate; Calcd: C, 58.41; H,
4.52; N, 15.72; S, 12.01.
Found: C, 58.71; H, 4.69;
N, 15.50; S, 12.56
(KBr) 3442, 2927,
1672, 1585, 1552,
1518, 1459, 1268
3429, 2921, 1659,
1504, 1508, 1429,
770
8.69 (dd, 1H, J ) 1.5, 4.7 Hz), 8.57(br d, 1H, J ) 4.7
Hz), 7.98(d, 1H, J ) 7.8 Hz), 7.9 (dd, 1H, J ) 1.5,
7.7 Hz), 7.82 (ddd, 1H, J ) 1.4, 7.7, 7.8 Hz), 7.44
(t, 1H), 7.32 (dd, 2H, J ) 4.7, 7.7 Hz), 2.098 (t, 2H),
1.998 (t, 2H)
Found: C, 59.59; H, 4.83; N,
15.95; S, 12.25
Ta ble 6. Th e Syn th eses of Di[10-(2,2′-bip yr id in e-5- a n d 4-ca r boxa m id o)d ecyl] Disu lfid es (5b, a n d c, n ) 10) fr om
2,2′-Bip yr id in e-5- a n d 4-ca r boxylic Acid (4b, a n d c) a n d Di(10-a m in od ecyl) Disu lfid e10
Anal. Calcd for C42H56N6O2S2
product
no.
yield,
%
(750.1): C, 66.45; H, 7.43; N,
11.00; S, 8.44
mp, °C
IR (KBr), ν cm-1
1H NMR (CDCl3), δ
5b n ) 10 131-133
64
3452, 2929, 2856,
1660, 1590, 1523,
1459
9.0 (d, 1H, J ) 2.1 Hz), 8.69 (d, 1H, J ) 4.8 Hz),
8.43 (dd, 2H, J ) 8.2, 8.2 Hz), 8.18 (dd, 1H,
J ) 2.1, 8.2 Hz), 7.83 (ddd, 1H, J ) 1.8, 7.8,
8.2 Hz), 7.34 (m, 1H), 6.17 (t, 1H), 3.8 (q, 2H),
2.67 (t, 2H), 1.6 (m, 4H), 1.3-1.2 (m, 12H)
8.78 (d, 1H), 8.68 (dd, 1H, J ) 1.8, 4.77 Hz),
8.6 (d, 1H, J ) 1.6 Hz), 8.44 (dd, 1H, J ) 1.5,
7.7 Hz), 7.85 (ddd, 1H, J ) 1.89, 7.75, 7.7 Hz),
7.76 (dd, 1H, J ) 1.64, 4.9 Hz), 7.36 (m, 1H),
6.65 (t, 1H), 3.5 (q, 2H), 2.65 (t, 2H), 1.7 (m,
4H), 1.4-1.0 (m)
semihydrate; Calcd: C, 67.25;
H, 7.52. Found: C, 67.13; H,
7.93
5c n ) 10 109-110
64
3414, 3297, 2913,
2844, 1630, 1525
Found: C, 66.78; H, 7.81; N,
10.44; S, 8.36
showed absorptions at 446-452 nm for the d-π* metal-
to-ligand charge-transfer transitions. The most intense
peaks at 298-301 nm were assigned to the intraligand
π-π* transitions.
Self-assembled monolayers of compounds 9-14 (Chart
1) were prepared on gold(111) substrates and examined
with cyclic voltammetry in 1.0 M HClO4. However, these
surface-bound complexes produced poorly defined volta-
mmetric responses due to the concurrent oxidation of the
gold surface. Similar results were reported by Obeng and
Bard1 for a thiol-functionalized tris(bipyridyl)ruthenium-
(II) complex immobilized on gold similar to those exam-
ined here. Thus, it was necessary to use Sb-doped SnO2
(ATO) substrates (Corning Pyrex brand infrared reflect-
ing glass) in order to obtain good quality voltammograms.
All of the tris(2,2′-bipyridyl)ruthenium(II) complexes
listed above chemisorbed on ATO, some to a greater
extent than others. Figure 1 shows a typical cyclic
voltammogram of an ATO substrate modified with 13.
For a series of voltammograms similar to that shown in
Figure 1, a plot of the voltammetric oxidation peak
current varied linearly with the scan rate as expected
for a surface-bound redox center.17 Voltammetric data for
complexes 9-14 chemisorbed on ATO substrates are

1018 J . Org. Chem., Vol. 64, No. 3, 1999
Notes
Ch a r t 1
Ta ble 7. Electr och em ica l Resu lts of Su bstitu ted
2,2′-Bip yr id ylr u th en iu m Com p lexes
SAMs on ATO electrodesa
in solutionb
E° ∆Ep
(V) (mV)
product subst.
no.
E°
∆Ep ∆Efwhm
Γc
position (V) (mV) (mV)
(mol/cm2)
9
10
11
12
13
14
6
5
5
4
4
3
1.08 51
1.07 61
1.11 47
1.08 46
1.11 34
110
163
140
141
130
3.6 × 10-12
1.0 × 10-11 1.31
1.6 × 10-11 1.30
8.3 × 10-12 1.31
2.7 × 10-11 1.30
86
86
94
96
83
very low
1.30
a
Versus SCE as determined by cyclic voltammetry in aqueous
b
1.0 M HClO4; the scan rates were 100 mV/s. Versus SCE as
determined by cyclic voltammetry at a Pt disk working electrode
in acetonitrile containing 0.1 M [n-Bu4N]PF6, the scan rates were
100 mV/s. c Equilibrium surface coverages of 9-14 on antimony-
doped tin oxide.
F igu r e 1. Cyclic voltammogram of the 2,2′-bipyridylruthe-
nium complex with di[10-(2,2′-bipyridine-4-carboxamido)decyl]
disulfide (13).
counterpart. These potentials indicate that those com-
plexes with shorter tethers (10 and 12) are 30-40 mV
easier to oxidize than those with the longer tethers (11
and 13). The voltammetric peak separation, ∆Ep, is
inversely proportional to the electron-transfer rate of
redox couples in solution or immobilized on electrode
surfaces. For a Nernstian redox couple confined to a
surface, ∆Ep approaches 0 V, whereas for a freely
diffusing species in solution, ∆Ep should be close to 0.059
V at 25 °C. The data in Table 7 show that ∆Ep exceeds
these theoretical expectations for all of the complexes
investigated both in solution and immobilized on gold
electrodes. Among the surface-bound species, the most
facile electron transfer was observed for films prepared
from 13. However, in solution, 13 exhibited the slowest
electron-transfer rate. The voltammetric oxidation peak-
width at half-maximum, Efwhm, is a measure of the lateral
interactions between adjacent surface-bound redox cen-
ters.18 It should be 90.3/n mV, where n is the number of
electrons involved in the redox reaction. Despite the
relatively low surface coverages found for 9-13, the
values of Efwhm are considerably larger than the 90.3 mV
value expected for an ideal one-electron surface reaction,
indicating substantial repulsive interactions between
adjacent redox centers.
collected in Table 7. The equilibrium surface coverage
(Γ) of each monolayer was estimated from the charge
under the voltammetric wave after correction for the
charging current. Voltammetric waves consistent with
surface-confined 14 could be detected; however, the
surface coverage of this complex was so small that
meaningful electrochemical data could not be extracted
from these voltammograms. However, the surface cover-
ages of the remaining complexes were comparable to that
reported by Obeng and Bard,1 ∼1.8 × 10-11 mol/cm2. This
value is attributed to about 10% of a full monolayer (1.8
× 10-10 mol/cm2). Although no clear trend can be seen,
the highest surface coverages appear to favor those
complexes with the longest side chains (11 and 13); the
long alkyl tethers probably facilitate surface packing. The
formal potential (E°) of each of the surface-confined
complexes is also listed in Table 7 along with its solution
(14) Haginiwa, J .; Higuchi, Y.; Hirawata, Y.; Hoshino, N.; Sakakura,
H. Yakugaku Zasshi 1979, 99, 1176; Chem. Abstr. 1980, 93, 26277z.
(15) Tingoli, M.; Tiecco, M.; Testaferri, L.; Andrenacci, R.; Balducci,
R. J . Org. Chem. 1993, 58, 6097.
(16) Imperiali, B.; Prins, T. J .; Fisher, S. L. J . Org. Chem. 1993, 58,
1613.
(17) Bard, A. J .; Faulkner, L. R. Electrochemical Methods; J ohn
Wiley & Sons: New York, 1980.
(18) Laviron, E. J . Electroanal. Chem. 1974, 52, 395-402.

Notes
J . Org. Chem., Vol. 64, No. 3, 1999 1019
Ta ble 8. Sp ectr a a n d An a lyses of th e 2,2′-Bip yr id ylr u th en iu m Com p lexes P r ep a r ed in Th is Wor k
complex
(mp °C)
UV (CH3CN),
abs λ (nm)
source
1H NMR (CD3CN), δ, J (Hz)
analyses (%)
9 (169-173) 3a
8.6-8.51 (m, 6H), 8.1-8.09 (m, 6H), 7.81-7.35 210, 300, 431, Calcd for C68H58F24N12O4P4Ru2S2: C,
(m, 11H), 4.75 (d, 1H, J ) 14.1), 4.21 (d, 1H,
J ) 14.1), 2.79 (t, 2H), 2.60 (t, 2H)
8.57-8.54 (m, 5H), 8.1 (m, 6H), 7.8 (m, 6H),
7.45 (m, 7H), 2.9 (t, 2H), 2.8 (t, 2H)
446
41.81; H, 2.99; N, 8.60; S, 3.28. Found: C,
41.85; H, 3.12; N, 8.17; S, 3.31
10 (214-216) 5b n ) 2
210, 241, 298, Calcd for C66H56F24N14O2P4Ru2S2: C,
452
41.22; H, 2.93; N, 10.14; S, 3.33. Found: C,
41.57; H 3.36; N, 9.74; S, 3.63
11 (189-191) 5b n ) 10 8.60-8.54 (m, 6H), 8.33 (m, 1H) 8.13-8.02
(m, 6H), 7.83-7.7 (m, 5H), 7.47-7.43 (m,
5H), 7.18 (t, 1H), 3.48 (q, 2H), 2.75-2.70
(t, 2H), 1.68-1.66 (m, 2H), 1.51-1.31
(m, 16H)
220, 300, 448 Calcd for C82H88F24N14O2P4Ru2S2‚1H2O:
C, 45.50; H, 4.14; N, 9.06; S, 2.96. Found:
C, 45.13; H, 4.16; N, 9.00; S, 3.33
12 (237-239) 5c n ) 2
8.83 (d, 1H), 8.55 (br d, 1H), 8.57-8.54 (br d,
4H), 8.15-8.08 (m, 5H), 7.9 (d, 1H), 7.78-
7.44 (m, 7H), 7.48-7.44 (m, 5H), 3.79 (q,
2H), 3.01 (t, 2H)
299, 320, 450 Calcd for C66H56F24N14O2P4Ru2S2‚1H2O:
C, 40.85; H, 3.01; N, 10.10; S, 3.33. Found:
C, 40.85; H 3.06; N, 9.86; S, 3.53
13 (172-174) 5c n ) 10) 8.8 (d, 1H), 8.6 (d, 1H), 8.56 (m, 4H), 8.14
(m, 5H), 7.91 (d, 1H), 7.7 (m, 7H), 7.47
(m, 5H), 3.4 (t, 2H), 2.7 (t, 2H), 1.7 (m,
4H), 1.6 (m, 12H)
210, 240, 301, Calcd for C82H88F24N14O2P4Ru2S2: C,
451
45.50; H, 4.14; N, 9.06. Found: C, 45.77;
H, 4.46; N, 8.51
14 (228-230) 5d
8.6-8.5 (m, 4H), 8.4 (m, 1H), 8.2-7.9 (m,
6H), 7.89-7.7 (m, 6H), 7.55-7.45 (m, 6H),
3.95-3.8 (t, 2H), 3.1 (t, 2H)
200, 298, 450 Calcd for C66H56F24N14O2P4Ru2S2: C,
41.22; H, 2.93; N, 10.14; S, 3.33. Found:
C, 40.88; H 3.09; N, 9.79; S, 3.62
as the working electrode. The reference electrode for all experi-
ments was an EG&G saturated calomel electrode (SCE) sepa-
rated from the working electrode compartment by means of a
Luggin capillary. All potentials mentioned in this paper were
measured with respect to this reference electrode. The counter
electrode was a platinum wire spiral. The electrolyte solutions
used for aqueous experiments were 1.0 M aqueous HClO4 and
a pH ) 7.2 phosphate buffer solution (Aldrich Chemical Co.).
Nonaqueous experiments were conducted in anhydrous aceto-
nitrile containing 0.1 M [n-Bu4N]PF6. All measurements were
conducted at ca. 24 °C. The solutions in the electrochemical cells
were deaerated with high purity N2 before each experiment, and
an atmosphere of N2 was maintained over the solution in the
cell during measurements. Electronic resistance compensation
was employed during all experiments. The equilibrium surface
coverage, Γ, reported for each monolayer was estimated from
the charge under the appropriate voltammetric oxidation or
reduction wave after subtraction of the residual current.
Gen er a l Syn th etic Ch em istr y. The following techniques
were followed unless otherwise stated. All reactions sensitive
to air and moisture were carried out in flame-dried apparatus,
under a dry nitrogen atmosphere using either magnetic or
mechanical stirring. All melting points were determined on a
Thomas-Hoover Unimelt apparatus and are uncorrected. Infra-
red spectra were recorded using KBr pellets or thin liquid films.
1H and 13C NMR spectra were determined on a 300 MHz
spectrometer using CDCl3, DMSO-d6, acetone-d6, or CD3CN with
tetramethylsilane (Me4Si) as the internal standard. Column
chromatography was carried out by gravity using 80-200 mesh
neutral alumina (Fisher, A-540-3) or E. Merck silica gel (9385).
Thin-layer chromatography was performed on Analtech neutral
alumina plates (2.5 cm × 10 cm, no. 47031) with a fluorescence
indicator. TLC spots were visualized either by exposure to iodine
vapors or by irradiation with UV light. Table 8 lists the
spectroscopic and analytical data of the major products. Elemen-
tal analyses were performed by Galbraith Laboratories, Inc.,
Knoxville, TN, or Atlantic Microlab, Inc., Norcross, GA.
We have successfully synthesized nine new 2,2′-bi-
pyridines substituted at four different positions with
disulfide-terminating chains. Six of them were complexed
with ruthenium II and the resultant products were
fabricated into self-assembled monolayers. Certain elec-
trochemical parameters were evaluated with respect to
the position of the disulfide substituent and the length
of the carbon chain between the disulfide and the redox
center.
Exp er im en ta l Section
Gen er a l Electr och em istr y. Acetonitrile (Fisher Optima
grade) was distilled from CaH2 under nitrogen, passed through
activated alumina, and stored in a tightly capped bottle over 4
Å molecular sieves until needed. Dehydrated absolute ethanol
was used as received from McCormick Distilling Co., Inc. Tetra-
n-butylammonium hexafluorophosphate (TBAHFP) was synthe-
sized and purified according to standard procedures. Standard
glass microscope slides (Fisher cat. no. 12-549) served as gold
substrates; they were cleaned by ultrasonication in successive
baths of piranha solution (1:3 by volume 30% H2O2/concentrated
H2S04), distilled water, and 2-propanol (Fisher Optima grade).
The oven-dried microscope slides were coated with 50 Å of
chromium followed by 1500 Å of gold by thermal evaporation at
a base pressure of 7 × 10-7 Torr by using an Edwards Auto 306
vacuum coater equipped with a Sycon Model STM-100/MF thin
film monitor. After coating was complete, the vacuum chamber
was back-filled with high-purity nitrogen gas. The gold films
prepared by this method were found by X-ray diffraction analysis
to exhibit strong Au {111} crystallographic texture.19 The gold
electrodes were taken directly from the vacuum coater and
immersed in solutions containing 9-14. Cyclic voltammetric
measurements were made in a three-electrode cell with an EG
& G Princeton Applied Research Corp. (PARC) Model 283
potentiostat/galvanostat employing PARC Model 270 Electro-
chemistry Analysis Software running on an IBM-compatible 386
computer. For studies with self-assembled monolayers, the gold-
coated substrates served as the working electrodes. They were
clamped to an O-ring joint attached to the side of the cell. The
O-ring provided a liquid-tight seal and defined the area of the
working electrode, which was ca. 1.54 cm2. For electrochemical
experiments involving solutions in acetonitrile, a small Kel-F
shrouded platinum disk electrode (area ) 0.0214 cm2) served
The following reagents were prepared as follows: 2-trimeth-
ylstannylpyridine, by the method of Yamamoto;7 methyl 2-chlo-
ropyridine-2-carboxylate (mp 96 °C), via esterification of 6-hy-
droxypicolinic acid (Aldrich); methyl 2-chloropyridine-3-carboxylate
(mp 64-65 °C), via esterification of the free acid (Maybridge-
Ryan Scientific); methyl 2-chloropyridine-4-carboxylate (mp 38-
40 °C), via esterification of 2-chloroisonicotinic acid;13 methyl
2-chloropyridine-5-carboxylate, via esterification of the free acid
(Maybridge-Ryan Scientific).
Gen er a l P r oced u r e for th e P r ep a r a tion of Meth yl 2,2′-
Bip yr id in eca r boxyla tes (1). A mixture of one of the methyl
chloropyridinecarboxylates (2.9 mmol), 2-trimethylstannylpyri-
dine (3.3 mmol), and (PPh3)2PdCl2 (0.15 mmol) in 10 mL of an
(19) He, Z.; Bhattacharyya, S.; Cleland, W. E. J .; Hussey, C. L. J .
Electroanal. Chem. 1995, 397, 305.

1020 J . Org. Chem., Vol. 64, No. 3, 1999
Notes
anhydrous solvent was heated for a period of time (see Table
1). During the course of this reaction, the color changed from
yellow to black as Pd° was formed. The solvent was removed,
and the residue was dissolved with CH2Cl2 and filtered through
a bed of silica gel and Celite. The pale yellow eluate was
evaporated and the residue was purified on a neutral alumina
column.
added dropwise to this mixture. The formation of a precipitate
was noted as the acid chloride was added, and the resulting
mixture was stirred at room temperature for 2 h and refluxed
for an additional 2 h. An orange-red precipitate or oil was
obtained after evaporation of the solvents. This residue was
dissolved in water, and the solution was made just slightly
alkaline with dilute hydrochloric acid to give a light yellow solid.
The crude solid, 5b, was purified by several recrystallizations
from CH2Cl2/hexane mixtures and finally from hot chloroform.
Crude 5c was a brown oil which was purified by chromatography
over a neutral alumina column using a 1.0 parts of EtOAc:1.0
parts of CH2Cl2:10 parts of hexane. Recrystallization from
chloroform afforded the product. See Table 6 for data on these
products.
Gen er a l P r oced u r e for th e P r ep a r a tion of (Hyd r oxy-
m eth yl)-2,2′-bip yr id in es (2). To a solution of one of the methyl
2,2′-bipyridinecarboxylates (1a , b, or c) (5 mmol) in anhyd THF
(20 mL) at -78 °C was added lithium aluminum hydride (5
mmol). The mixture was stirred at this temperature for 0.5 h
and was warmed slowly to -20 °C, at which temperature, a
homogeneous solution was obtained. The reaction was monitored
with TLC on alumina, and the complete disappearance of the
starting material was noted after 1 h. The reaction mixture was
cooled to -78 °C and quenched very slowly with 10 mL of 10%
aqueous THF. After being warmed to room temperature, the
reaction mixture was stirred with Celite for 15 min and then
filtered. The filtrate was concentrated and extracted with
methylene chloride, and the extract was dried over anhyd
MgSO4. Evaporation of the solvent yielded 2a , b,16 and c as
yellow oils. They were homogeneous by TLC and were used, as
is, for further transformations. See Table 2 for yields and
spectral data.
Gen er a l P r oced u r e for th e P r ep a r a tion of Di[(2,2′-
bip yr id in yl)m eth yl] 3,3′-Dith iod ip r op a n oa tes (3). A mix-
ture of one of the 6-, 5-, or 4-(hydroxymethyl)-2,2′-bipyridines
(2a , b, or c) (0.6 mmol), dicyclohexylcarbodiimide (0.6 mmol),
3,3-dithiodipropanoic acid (0.3 mmol), and pyrrolidinopyridine
(0.1 mmol) was stirred in dry CH2Cl2 (10 mL) at room temper-
ature for about 2 days. Dicyclohexylurea precipitated and was
filtered. The filtrate was concentrated to an oil, and this was
purified on a neutral alumina column to yield a white solid.
Recrystallization from EtOAc/hexane afforded 3a and b as white
crystals and 3c as an oil. See Table 3 for data on these products.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e 2,2′-
Bip yr id in eca r boxylic Acid s (4). Five mmol of one of the
methyl 2,2′-bipyridine-5, 4, or 3-carboxylates (1b, c, or d ) was
dissolved in hot methanol (5 mL) to which was added 1 N NaOH
(5 mL) and the reaction mixture was stirred at room temperature
for 3-5 h. A TLC was used to check for any remaining starting
material. The solvent was removed under reduced pressure, and
the aqueous phase was acidified with 0.5 N HCl to pH 3.5-4.0.
A white precipitate separated upon cooling. It was collected by
filtration, washed with water, and air-dried. Pure white crystals
were obtained. See Table 4 for data on these products.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e Di[2-(2,2′-
bip yr id in eca r boxa m id o)eth yl] Disu lfid es (5, n ) 2). Oxalyl
chloride (5 mmol) in 2.5 mL of CH2Cl2 was added to a stirred
solution of 2,2′-bipyridine-5-, 4-, or 3-carboxylic acid (2.5 mmol,
4b, c, or d ) in THF (8 mL). The mixture immediately turned
green and a precipitate formed. This mixture was refluxed for 2
h. The solvent and the excess oxalyl chloride were removed
under reduced pressure. The acid chloride was dissolved in 3
mL of dry THF and was added to a solution of cystamine
dihydrochloride (1.25 mmol) in 2.5 equiv of aqueous NaOH. The
mixture was stirred at room temperature for 3 h and refluxed
for an additional 3 h. The solvent was removed, and the residue
was dissolved in water. The pH of the solution was made slightly
alkaline and the product precipitated as a brown solid. This
crude product was purified by column chromatography on
neutral alumina using 0.5 parts of MeOH:4.0 parts of CH2Cl2:
6.0 parts of hexane for 5b, 0.5 parts of MeOH:5.0 parts of CH2-
Cl2:6.0 parts of hexane for 5c, and 1.0 parts of EtOAc:1.0 parts
of CH2Cl2:10 parts of hexane for 5d . Recrystallization from CH2-
Cl2/hexane afforded a white solid product. See Table 5 for data
on these products.
Gen er a l P r oced u r e for t h e P r ep a r a t ion of t h e Di[10-
(2,2′-bip yr id in eca r boxa m id o)d ecyl] Disu lfid es (5, n ) 10).
A stirred solution of 2,2′-bipyridine-5 or 4-carboxylic acid (0.8
mmol, 4b or c) in THF (5 mL) was treated with 3 equiv of oxalyl
chloride. The resulting green precipitate was refluxed for 2 h at
70 °C and the solvents were evaporated under vacuum. In
another flask, a solution of di(10-aminodecyl) disulfide10 was
prepared by dissolution of the dihydrochloride (0.35 mmol) in
water (0.5 mL) and NaOH (1.0 mmol). The acid chloride was
5-(Am in om eth yl)-2,2′-bip yr id in e (7). This procedure was
reported by Ziessel and Lehn for the preparation of 6-(amino-
methyl)-2,2′-bipyridine.20 A 25-mL round-bottom flask fitted with
a reflux condenser was charged with hexamethylenetetramine
(0.39 g, 2.8 mmol) and methylene chloride (5 mL). The mixture
was heated to reflux, and a solution of 5-(bromomethyl)-2,2′-
bipyridine (6)16 (0.6 g, 2.4 mmol) in CH2Cl2 (1 mL) was added
dropwise and refluxed an additional 3 h. The deposited white
solid was filtered, dried, and suspended in EtOH (10 mL) and
concentrated HCl (2 mL). The mixture was stirred at 80 °C for
20 h during which time the solid dissolved. The solution was
cooled to room temperature, and the solvents were evaporated
under reduced pressure. Water (5 mL) and chloroform (10 mL)
were added to the residue, and the mixture was adjusted to pH
13 with a solution of NaOH. The aqueous phase was extracted
with methylene chloride (3 × 20 mL), and the combined organic
extracts were dried over anhyd MgSO4. The crude amine (440
mg, 98%) was obtained after evaporation of the solvents. It was
used as is or was stored as the hydrochloride salt. 1H NMR (free
amine) (CDCl3): δ 8.68 (dq, 1H), 8.62 (d, 1H), 8.37 (2H), 7.8
(overlapping ddd, 2H), 7.29 (m, 1H), 3.96 (s, 2H), 1.64 (s, 2H).
Di{N-[(2,2′-b ip yr id -5-yl)m et h yl]}-3,3′-d it h iod ip r op a n a -
m id e (8). A mixture of 3,3-dithiodipropanoic acid (0.17 g, 0.81
mmol), THF (5 mL), and oxalyl chloride (1.6 mmol, 0.8 mL of a
2 M solution in CH2Cl2) was stirred at room temperature
overnight and then refluxed for 2 h. The volatile components
were evaporated under a stream of nitrogen at reduced pressure,
and the residue was dissolved in anhyd THF (5 mL). To this
mixture was added 5-(aminomethyl)-2,2′-bipyridine (7) (0.39 g,
1.62 mmol) dropwise, the whole reaction mixture was stirred at
room temperature for 6 h, and then refluxed for an additional 2
h. The solvent was evaporated under vacuum, the residue was
dissolved in water, and the pH was adjusted to 8. The product
precipitated as a light brownish solid that weighed 0.35 g. It
was then recrystallized from hot methanol and a cream-colored
solid, 8, was obtained (0.29 g, 66%), mp 164-165 °C. IR (KBr):
ν 3438, 3013, 2926, 1731, 1686, 1514, 1461, 1194, 760 cm-1; 1H
NMR (CDCl3): δ 8.64 (dd, 1H, J ) 0.7, 4.0 Hz), 8.54 (d, 1H, J )
2.0 Hz), 8.28 (br t, 2H, J ) 7.9, 8.1 Hz), 7.76 (ddd, 1H, J ) 0.7,
7.8, 7.9 Hz), 7.69 (dd, 1H, J ) 2.0, 8.1 Hz), 7.29 (dd, 1H, J )
4.0, 7.8 Hz), 6.9 (t, 1H, J ) 5.9 Hz), 4.43 (d, 2H, J ) 5.9 Hz),
2.96 (t, 2H), 2.60 (t, 2H). Anal. Calcd For C28H28N6O2S2: C,
61.74; H, 5.18; N, 15.42; S, 11.77. Found: C, 61.72; H, 5.36; N,
14.99; S, 11.38.
Gen er a l Meth od for th e P r ep a r a tion of Six 2,2′-Bip y-
r id ylr u th en iu m Com p lexes w ith Disu lfid e-F u n ction a lized
2,2′-Bip yr id in es. In a typical experiment, cis-dichlorobis(2,2′-
bipyridine)ruthenium(II) dihydrate (2 equiv) was suspended in
ethanol solution to which was added 1 equiv of the appropriate
ligand. The resulting mixture was deaerated with N2 for about
15 min using a syringe needle, and the mixture was heated at
reflux for 6-12 h with vigorous magnetic stirring. After the
reflux period, the dark red-orange solution was evaporated to
one-third of the initial volume, and water (20 mL) was added.
The unreacted cis-Ru(bipy)2Cl2‚2H2O was removed by filtration.
An excess of ammonium hexaflurophosphate was added, and the
flocculent orange-to-red precipitate that appeared was collected.
The product was washed with copious amounts of water followed
by ether and was air-dried. The complexes were purified initially
(20) Ziessel, R.; Lehn, M.-J . Helv. Chim. Acta 1990, 73, 1149.

Notes
J . Org. Chem., Vol. 64, No. 3, 1999 1021
by column chromatography on neutral alumina using 9:1 CH2-
Cl2:MeOH followed by a few recrystallizations from acetone-
ether or acetonitrile-ether mixtures. Crude yields ranged from
80 to 95% and the purified yields were about 70-85%. See Table
8 for data on these red/orange complexes.
Ack n ow led gm en t. The work was supported by the
National Science Foundation-Mississippi EPSCoR Project
(grant EPS 95-01-219).
J O9814795