The triphenylmethyl group as thiol protection during ruthenium-promoted synthesis of tetraalkyl-p-phenylenediamine systems having alkanethiol side chains

Article abstract of DOI:10.1016/S0040-4020(00)01145-5

The use of triphenylmethyl as thiol protecting group during the construction of thioalkyl-substituted tetraalkyl-p-phenylenediamine derivatives, via arene-ruthenium chemistry, is reported.

Full text of DOI:10.1016/S0040-4020(00)01145-5

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1489±1495
The triphenylmethyl group as thiol protection during
ruthenium-promoted synthesis of tetraalkyl-p-phenylenediamine
systems having alkanethiol side chains
Anthony J. Pearsonp and Jiunn-Jye Hwang
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
Received 3 November 2000; accepted 6 December 2000
AbstractÐThe use of triphenylmethyl as thiol protecting group during the construction of thioalkyl-substituted tetraalkyl-p-phenylene-
diamine derivatives, via arene±ruthenium chemistry, is reported. q 2001 Elsevier Science Ltd. All rights reserved.
N,N,N0,N0-Tetramethyl-p-phenylenediamine (TMPD), is a
powerful organic donor molecule, ®rst described in 1879
by Wurster,1 the redox properties of which have received
considerable attention.2 The ®rst and only self-assembled
monolayers (SAMs) of TMPD derivatives, having a single
N-thioalkyl side chain, have been shown to be more easily
oxidized, by electrochemical methods, than TMPD itself.3
Because of dif®culties in their preparation using standard
methodology, very few functionalized tetraalkyl-p-phenyl-
enediamine (TAPD) derivatives are readily available.4 Over
the past several years we have developed an approach to the
synthesis of a wide range of these molecules, using tran-
sition-metal promoted SNAr reactions of chloroarenes,5 and
we have reported on their redox properties,6 as well as the
photoinduced electron transfer characteristics of Donor±s±
Acceptor (D±s±A) systems that use the TAPD as the donor
unit.7 The general reaction is outlined in Eq. (1). The use of
a transition metal moiety for this process has several
advantages, among which is protection of the readily oxi-
dizable TAPD system during numerous synthetic operations.
ꢀ1†
Recently, we reported8 an approach to the construction of
D±s±A molecules that have thioalkyl side chains, via
sequential SNAr reactions on [(1,4-dichlorobenzene)-
RuCp]1[PF6]2 (1), summarized in Scheme 1. Such
compounds, and related systems, might be useful as, e.g.
unimolecular recti®ers,9 currently under investigation in
Scheme 1.
Keywords: N,N,N0,N0-tetramethyl-p-phenylenediamine; self-assembled monolayers; arene±ruthenium.
Corresponding author. Tel.: 11-216-3683620; fax: 11-216-3683006; e-mail: ajp4@po.cwru.edu
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01145-5

1490
A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
Scheme 2.
Scheme 3.
our laboratories, since they can be used to construct mono-
layers on, e.g. nanostructured gold10 or platinum11 surfaces.
The approach we described earlier, in which bis(piperazi-
noalkyl)disul®des are used as the latent thiol groups, suffers
the disadvantage of requiring very long reaction times
(.17 d) for high-yielding bis(arylation) of the long-chain
diamine, the reasons for which are presently unknown. In
order to access the ultimate product D±s±A compounds
more conveniently, we have investigated an approach that
uses alternative thiol protection during the SNAr reactions.
We describe herein the use of the triphenylmethyl group,
which we have found to be well-suited for this purpose, with
the advantage that its removal can be effected in the
presence of the arene±RuCp system, thereby maintaining
protection of the sensitive TAPD molecule until it is
released by controlled demetallation.
For these studies we have used, as the ®rst nucleophile, 1-(8-
triphenylmethylthiooctyl)piperazine (2), obtained in 98%
yield by reacting the known 1-bromo-8-triphenyl-
methylthiooctane12 with excess piperazine in EtOH at
re¯ux. Reaction of 2 with 1 proceeded smoothly at room
temperature, and required only 90 h for completion (in
contrast to .400 h for the aforementioned disul®de deriva-
tive). The product 3 was obtained in 91% yield. Complex 3
was reacted with several cyclic amine nucleophiles to afford
the TAPD complexes 4±7 (Scheme 2). In addition, the
piperazine derivative 4 was readily converted to the N-
acyl (acylˆacceptor) systems 8 and 9 (Scheme 3); the
triphenylmethyl thioether was stable during all of these
transformations, as expected.
Deprotection of the thiol might be accomplished either on
Scheme 4.
Scheme 5.

A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
1491
Scheme 6.
the complexes or on the TAPD derivatives that result from
demetallation. Initially, the decomplexation of complexes
5±7 was performed prior to trityl removal, by exposure of
the complexes to UV light (Rayonet reactor) in aqueous
ammonia±acetonitrile. This was accompanied in some
cases by concomitant partial or complete loss of the trityl
group; further treatment of the crude products with
PhHgOAc, then H2S in CH2Cl2±CH3OH,13 completed the
Table 1. Redox potential of derivatized p-phenylenediamines and TTFs
a
E1,1/2 (mV)
p-phenylenediamine
TTF
TMPD
DPPD
174
230
TTF
401
380b
420c
400b
485b
590c
540c
650d
730d
13
14
15
17
18
289
389
342
418
423
BEDO-TTF
BEDT-TTF
22
23
24
25
a
Experimental conditions: 1 mM substrate, 0.1 M Bu4NPF6 vs Ag/AgCl in CH2Cl2.
Ref. 14(a), vs Ag/AgCl in CH2Cl2, ®rst oxidation potential.
Ref. 14(b), vs Ag/AgCl in benzonitrile.
b
c
d
Ref. 14(a,c), vs Ag/AgCl in THF, SAM.

1492
A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
deprotection to afford the disul®des shown (formed as a
result of oxidation of the thiols during isolation and puri®-
cation). Thus, decomplexation of 5 and 6 afforded directly
the disul®des 13 and 14, respectively, with no isolation of 10
or 11, while 7 gave a mixture of 12 and 15, and 8 gave 16,
the latter without loss of the trityl group (Schemes 4 and 5).
dichlorobenzene)ruthenium hexa¯uoro-phosphate8 and
8-(triphenylmethylthio)-1-bromooctane12 were prepared by
literature procedures. Demetallation was performed in a
Rayonet apparatus (350 mm). Mercury residues from depro-
tection reactions are generally set aside for collection and
disposal by insitutional safety services personnel.
Conversion of the 12/15 mixture to 15, and of 16 to 17 was
straightforward. It may be noted that disul®des can be used
directly for the construction of surface-attached mono-
layers, so this is quite acceptable. We found that it is also
possible to detatch the triphenylmethyl group before
demetallation, and in several cases this allows easier
removal of (ether-soluble) triphenylmethyl byproducts, as
the ruthenium complexes are generally insoluble in diethyl
ether. The arene±ruthenium system is suf®ciently stable to
survive the deprotection conditions (PhHgOAc then H2S in
CH2Cl2±CH3OH), and the product complexes are again
obtained as disul®des. Examples are shown here for the
conversion of 5±7 to 19±21. Subsequent decomplexation
reactions were effected by the usual photochemical pro-
cedure in the presence of aqueous ammonia to free the
residual Ru(II) products from the piperazine diamine in
the product molecule, as detailed in Section 16,8 (Scheme 6).
Cyclic voltammetry was carried out using a CH Instruments
electrochemical analyzer. The supporting electrolyte (0.1 M
nBu4NPF6) was prepared using CH2Cl2 (HPLC grade) and
degassed for 30 min before use. nBu4NPF6 (electrochemical
grade) was purchased from Fluka Co. and used as received.
A glassy carbon (GC, f 3 mm) was used as a working
electrode, the counter electrode was a platinum wire, and
a Ag/AgCl electrode was used as the reference electrode.
Both the counter and the reference electrodes were directly
immersed in the electrolyte solution. The scan rate was
50 mV/sec. The potential of the regular ferrocene/
ferricinium couple was 470 mV under our experimental
conditions.
1.1.1. 1-(8-Triphenylmethylthiooctyl)-piperazine (2). A
mixture of piperazine (1.4 g, 16.2 mmol, 5 equiv.),
8-(triphenylmethylthio)-1-bromooctane (1.512 g, 3.23
mmol) in 55 mL 90% ethanol was re¯uxed overnight.
After removing the ethanol under reduced pressure, the
residue was made strongly alkaline with 1 M NaOH,
extracted with ether four times and dried over Na2SO4 to
We have carried out some preliminary cyclic voltammetry
studies on these compounds, and the results are summarized
in Table 1. The noteworthy feature of these data is that
functionalization of the TAPD system does not lead to
changes in redox potential of a magnitude that would
prevent utilization of the compounds as powerful electron
donors. This is in contrast to TTF systems, which generally
are less easily functionalized with retention of useful donor
capability, some examples of which are included in the
table for comparison.14 Thus, we anticipate that the
arene±ruthenium chemistry described herein will allow
access to a range of interesting molecules that have useful
donor±acceptor properties.
1
give product as an oil (1.5 g, 98%). H NMR (300 MHz,
CDCl3) d 7.18±7.43 (15H), 2.94 (t, Jˆ4.7 Hz, 2H), 2.45
(br s, 4H), 2.30 (t, Jˆ7.7 Hz, 2H), 2.14 (t, Jˆ7.1 Hz, 2H),
1.21±1.50 (15H); 13C NMR (75 MHz, CDCl3) d 145.0,
129.5, 127.7, 126,4, 66.3, 59.2, 53.8, 45.6, 31.9, 29.2,
29.0, 28.9, 28.5, 27.4, 26.5; HRMS Calcd for MH1
(C31H41N2S) 473.2990. Found: 473.2990.
1.1.2.
(h5-Cyclopentadienyl)(h6-(1-chloro-4-(4-(8-tri-
phenylmethylthiooctyl)-piperazino)-benzene]ruthenium
hexa¯uorophosphate (3). Cyclopentadienyl(1,4-dichloro-
benzene)ruthenium hexa¯uorophosphate (1, 0.615 g,
1.34 mmol) was stirred with K2CO3 (195 mg, 1.41 mmol,
1.05 equiv) and compound 2 (1.27 g, 2.68 mmol, 2 equiv) in
27 mL THF at rt for 90 h. After removing THF under
reduced pressure, ether was added. The mixture was stirred
for several hours, ether was decanted and fresh ether was
added. The procedure was repeated until all unreacted 1-(8-
triphenylmethyl-thiooctyl)-piperazine was removed. Then
the precipitate was collected, dissolved in acetone, ®ltered,
and the solvent was removed in vacuo to give the product as
an amorphous powder (1.094 g, 91%). 1H NMR (300 MHz,
d6-Acetone) d 7.26±7.45 (15H), 6.55 (d, Jˆ6.6 Hz, 2H),
6.17 (d, Jˆ6.6 Hz, 2H), 5.57 (s, 5H), 3.22 (t, Jˆ5.0 Hz,
4H), 2.57 (t, Jˆ5.0 Hz, 4H), 2.37 (t, Jˆ7.2 Hz, 2H), 2.19
(t, Jˆ7.2 Hz, 2H), 1.24±1.50 (12H); 13C NMR (75 MHz,
d6-Acetone) d 146.0, 130.3, 128.6, 127.4, 126.4, 101.7,
85.9, 81.2, 69.3, 67.1, 58.8, 52.7, 47.9, 32.1, 29.3, 29.0,
28.9, 28.5, 27.4, 26.5; FAB HRMS Calcd for M±
PF62(C42H48N2ClSRu, 102Ru) 749.2770. Found: 749.2259.
1. Experimental
1.1. General procedures
All reactions were performed under an inert atmosphere
(using dry, oxygen-free argon). All solvents used in the
reactions were freshly distilled under nitrogen as follows:
tetrahydrofuran from sodium/benzophenone, and methylene
chloride and acetonitrile from CaH2. Column chroma-
tography was performed on aluminium oxide (Aldrich
neutral or basic alumina (Brockman I)) or ¯ash grade silica
gel and the eluting solvents are reported as V/V percent
mixtures. Thin layer chromatography was performed on
E. Merck silica gel 60 F254 0.25 mm or Aluminium oxide
60 F254 0.25 mm plates and visualized with UV light. NMR
(1H or 13C) spectra were recorded on a Varian Gemini-300
(300 MHz) spectrometer using CDCl3 or acetone-d6 as
solvent. Infrared spectra were recorded for solutions in
methylene chloride or chloroform using a NaCl cell on a
Nicolet Impact 400 FTIR spectrophotometer. Accurate
masses (HRMS) are reported for the 102Ru isotope. All
new compounds were judged to be at least 95% pure accord-
ing to their 1H NMR spectra. Cyclopentadienyl-(1,4-
1.1.3. (h5-Cyclopentadienyl)(h6-1-(piperazino)-4-(4-(8-tri-
phenylmethylthiooctyl)-piperazino)benzene]ruthenium
hexa¯uorophosphate (4). Complex 3 (800 mg, 0.89 mmol)
was stirred with piperazine (308 mg, 3.58 mmol, 4 equiv)

A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
1493
and K2CO3 (247 mg, 1.78 mmol, 2 equiv) in THF (18 mL)
for 22 h at rt. After removing THF under reduced pressure,
ether was added. The mixture was stirred for several hours,
the ether was decanted and fresh ether was added. The
procedure was repeated until all unreacted piperazine was
removed. Then the precipitate was collected, dissolved in
acetone, ®ltered, and the solvent was removed in vacuo to
give the product as an amorphous powder (715 mg, 85%).
1H NMR (300 MHz, d6-Acetone) d 7.23±7.42 (15H), 5.80
(s, 4H), 5.42 (s, 5H), 3.03 (t, Jˆ4.7 Hz, 4H), 2.95 (br, 8H),
2.53 (t, Jˆ4.7 Hz, 4H), 2.32 (t, Jˆ7.2 Hz, 2H), 2.15 (t,
Jˆ7.2 Hz, 2H), 1.19±1.50 (12H); 13C NMR (75 MHz,
d6-Acetone) d 146.2, 130.5, 128.9, 127.6, 123.8, 123.1,
77.6, 68.4, 68.2, 67.3, 59.1, 53.1, 49.4, 48.6, 46.1,
32.7,31.9, 29.2, 29.0, 28.9, 28.2, 27.6; FAB HRMS Calcd
for M±PF62(C46H57N4SRu, 102Ru) 799.3347. Found:
799.3363.
with Ar for 30 min. The mixture was sealed in a pressure
tube and heated to 65±708C for 60 h. After removing the
THF under reduced pressure, CH2Cl2 was added. The
organic phase was washed with 1 M NaOH, H2O, and
brine and dried over Na2SO4 to give 7 as a powder
1
(360 mg, 85%) H NMR (300 MHz, CDCl3) d 7.17±7.42
(15H), 5.65 (d, Jˆ7 Hz, 2H), 5.61 (d, Jˆ7 Hz, 2H), 5.24 (s,
5H), 3.70 (s, 3H), 3.52 (br m, 2H), 2.93 (br s, 4H), 2.63 (br,
1H), 2.55 (br s, 6H), 2.33 (t, Jˆ7.2 Hz, 2H), 2.13 (t,
Jˆ7.2 Hz, 2H), 1.80±2.02 (4H), 1.21±1.43 (12H); 13C
NMR (75 MHz, CDCl3) d 174.6, 145.1, 129.6, 127.8,
126.6, 122.6, 121.8, 77.3, 67.4, 67.1, 66.4, 58.5, 52.1,
52.0, 47.7, 47.0, 39.8, 32.0, 29.3, 29.2, 29.0, 28.6, 27.4,
26.8, 26.5; IR (CH2Cl2) 1740 cm21; FAB HRMS Calcd
for M±PF62(C49H60N3O2SRu, 102Ru) 856.3450. Found:
856.3456.
1.1.7. (h5-Cyclopentadienyl)(h6-1-(4-(4-methoxycarbonyl-
benzoyl)piperazino)-4-(4-(8-triphenylmethylthiooctyl)-
1.1.4. (h5-Cyclopentadienyl)(h6-1-(piperidino)-4-(4-(8-tri-
phenylmethylthiooctyl)-piperazino)benzene]ruthenium
hexa¯uorophosphate (5). Complex 3 (269 mg, 0.3 mmol)
was stirred with piperidine (297 mL, 3 mmol, 10 equiv) and
K2CO3 (83 mg, 0.6 mmol, 2 equiv) in THF (5 mL) for 48 h
at rt. The solvent was removed and the residue was pumped
in vacuo for overnight. Then ether was added, the pre-
cipitate was collected and washed with ether several
times. The residue was dissolved in acetone and ®ltered,
and the ®ltrate was evaporated in vacuo to give the product
as an amorphous powder (259 mg, 91%). 1H NMR
(300 MHz, d6-Acetone) d 7.27±7.47 (15H), 5.89 (s, 4H),
5.48 (s, 5H), 3.16 (t, Jˆ4.9 Hz, 4H), 3.09 (t, Jˆ4.9 Hz,
4H), 2.58 (t, Jˆ4.9 Hz, 4H), 2.37 (t, Jˆ7.2 Hz, 2H), 2.19
(t, Jˆ7.2 Hz, 2H), 1.26±1.74 (18H); 13C NMR (75 MHz,
d6-Acetone) d 146.0, 130.4, 128.7, 127.5, 124.0, 122.7,
77.5, 68.3, 67.8, 67.2, 58.9, 53.0, 49.0, 48.4, 32.5, 29.9,
29.7, 29.6, 29.2, 28.0, 27.5, 25.4, 24.0; FAB HRMS Calcd
for M±PF62(C47H58N3SRu, 102Ru) 798.3395. Found:
798.3390.
piperazino)benzene]ruthenium
hexa¯uorophosphate
(8). The acid chloride from mono methyl terephthalate
(245 mg, 1.36 mmol, 3 equiv) and K2CO3 (188 mg,
1.36 mmol, 3 equiv) were stirred in 10 mL CH2Cl2.
Complex 4 (418 mg, 0.44 mmol) in 15 mL CH2Cl2 was
added and the mixture was stirred at rt for 18 h. Then 1 M
NaOH solution and CH2Cl2 were added and the mixture was
stirred for another 12 h. The organic phase was separated
and washed with 1 M NaOH, H2O, brine, and dried over
Na2SO4 and evaporated to give complex 8 as a powder
(465 mg, 92%).1H NMR (300 MHz, CDCl3) d 8.08 (d,
Jˆ8.2 Hz, 2H), 7.51 (d, Jˆ8.2 Hz, 2H), 7.17±7.42 (15H),
5.70 (d, Jˆ6.7 Hz, 2H), 5.60 (d, Jˆ6.7 Hz, 2H), 5.27 (s,
5H), 3.91 (s, 3H), 3.50±3.90 (br, 4H), 3.00 (br s, 4H),
2.93 (br s, 4H), 2.54 (br s, 4H), 2.32 (t, Jˆ7.2 Hz, 2H),
2.13 (t, Jˆ7.2 Hz, 2H), 1.21±1.41 (12H); 13C NMR
(75 MHz, CDCl3) d 169.4, 166.3, 145.1, 139.1, 131.6,
130.0, 129.6, 127.8, 127.4, 126.6, 122.3, 121.4, 77.3, 68.5,
67.3, 66.4, 58.5, 52.4, 52.0 (2C), 47.6 (2C), 32.0, 29.3, 29.2,
29.0, 28.6, 27.4, 26.8; IR (CH2Cl2) 1723, 1647 cm21; FAB
1.1.5. (h5-Cyclopentadienyl)(h6-1-(morpholino)-4-(4-(8-tri-
phenylmethylthiooctyl)-piperazino)benzene]ruthenium
hexa¯uorophosphate (6). The procedure is the same as for
compound 5. Complex 3 (235 mg, 0.263 mmol) was treated
with morpholine (230 mL, 2.6 mmol, 10 equiv) and K2CO3
(73 mg, 0.528 mmol, 2 equiv) in THF (5 mL) for 68 h at rt
to give the product as an amorphous powder (220 mg, 88%).
1H NMR (300 MHz, d6-Acetone) d 7.27±7.47 (15H), 5.86
(s, 4H), 5.49 (s, 5H), 3.84 (t, Jˆ4.9 Hz, 4H), 3.02±3.08 (m,
8H), 2.58 (t, Jˆ4.9 Hz, 4H), 2.37 (t, Jˆ7.2 Hz, 2H), 2.19 (t,
Jˆ7.2 Hz, 2H), 1.26±1.74 (12H); 13C NMR (75 MHz,
d6-Acetone) d 146.0, 130.4, 128.7, 127.5, 123.3, 122.8,
77.6, 68.5, 68.2, 67.2, 66.4, 58.9, 53.0, 48.4 (2C), 32.5,
29.9, 29.7, 29.5, 29.2, 28.0, 27.5; FAB HRMS Calcd
for M±PF62(C46H56N3OSRu, 102Ru) 800.3200. Found:
800.3196.
HRMS Calcd for M±PF6 (C55H63N4O3SRu, 102Ru)
2
961.3665. Found: 961.3661.
1.1.8. (h5-Cyclopentadienyl)(h6-1-(4-(anthraquinone-2-
carboxy)piperazino)-4-(4-(8-triphenylmethylthiooctyl)-
piperazino)benzene]ruthenium
hexa¯uorophosphate
(9). The procedure is the same as for compound 8. Complex
4 (385 mg, 0.406 mmol), the acid chloride from anthra-
quinone 2-carboxylic acid (308 mg, 1.22 mmol, 3 equiv)
and K2CO3 (168 mg, 1.22 mmol, 3 equiv) gave 9 as a
1
powder (393 mg, 82%). H NMR (300 MHz, CDCl3) d
8.22±8.33 (4H); 7.77±7.89 (3H); 7.17±7.42 (15H); 5.67
(d, Jˆ6.6 Hz, 2H), 5.55 (d, Jˆ6.6 Hz, 2H), 5.26 (s, 5H),
3.80±3.95 (br, 2H), 3.5±3.7 (br, 2H), 3.03 (br, 4H), 2.90
(br s, 4H), 2.53 (br s, 4H), 2.32 (t, Jˆ7.2 Hz, 2H), 2.13 (t,
Jˆ7.2 Hz, 2H), 1.20±1.43 (12H); 13C NMR (75 MHz,
CDCl3) d 182.2 (2C), 168.4, 145.1, 140.4, 134.5 (2C),
134.1, 133.6, 133.3 (2C), 132.8, 129.6, 127.8, 127.4 (2C),
126.6, 126.0, 122.2, 121.3, 77.4, 68.4, 67.2, 66.4, 58.5, 52.0
(2C), 47.6 (2C), 32.0, 29.3, 29.2, 29.0, 28.6, 27.4, 26.8; IR
1.1.6. (h5-Cyclopentadienyl)(h6-1-(4-methoxycarbonyl-
piperidino)-4-(4-(8-triphenylmethylthiooctyl)piperazino)-
benzene]ruthenium hexa¯uorophosphate (7). A solution
of complex 3 (380 mg, 0.425 mmol), (4-methoxycarbonyl)-
piperidine hydrochloride (305 mg, 1.70 mmol, 4 equiv),
with NaOH (68 mg, 1.70 mmol, 4 equiv) and K2CO3
(235 mg, 1.70 mmol, 4 equiv) in 7 mL THF was purged
(CH2Cl2) 1679, 1642 cm21; FAB HRMS Calcd for M±PF6
2
(C61H63N4O3SRu, 102Ru) 1033.3664. Found: 1033.3654.
1.1.9. (1-(4-(4-Methoxycarbonylbenzoyl)piperazino))(4-

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A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
(4-(8-triphenylmethylthiooctyl)piperazino))benzene (16).
A solution of complex 8 (56 mg, 0.05 mmol) in CH3CN/
TMEDA (12 mL/3 mL) was degassed for 30 min and
irradiated under UV light for 47 h. Basic alumina (Brockman
I) was added to the solution. After removing the solvent, the
alumina residue was dried in vacuo. This was placed atop a
short basic alumina column and the product was eluted with
chloroform. Further puri®cation by TLC (Merck Al2O3 plate)
with CHCl3 afforded analytically pure product as a ®lm
(21 mg, 53%). 1H NMR (300 MHz, CDCl3) d 8.10 (d,
Jˆ8.2 Hz, 2H), 7.50 (d, Jˆ8.2 Hz, 2H), 7.18±7.44 (15H),
6.90 (s, 4H), 3.95 (s, 3H), 3.94 (br, 2H), 3.60 (br, 2H), 3.16
(br, 6H), 3.01 (br, 2H), 2.64 (br, 4H), 2.40 (t, Jˆ7.2 Hz, 2H),
2.15 (t, Jˆ7.2 Hz, 2H), 1.22±1.60 (12H); IR (CH2Cl2) 1740,
1651 cm21; FAB HRMS Calcd for M (C50H58N4O3S)
794.4293. Found: 794.4228.
HRMS Calcd for M1 (C44H72N6O2S2) 780.5158. Found:
780.5143.
1.1.13. Bis[8-[4-[4-(4-methoxycarbonylpiperidino)phenyl)]-
piperazino]octyl] disul®de (15). The procedure is the same
as for compound 16. A solution of complex 7 (100 mg,
0.10 mmol) in CH3CN/NH3(aq) (10 mL/1.5 mL) was
degassed for 30 min and irradiated under UV light for
48 h to give 12 (20 mg, 22% yield) and 15 (9 mg, 20%
yield). 12: 1H NMR (300 MHz, CDCl3) d 7.18±7.45
(15H), 6.90 (s, 4H), 3.71 (s, 3H), 3.50 (m, 2H), 3.12 (t,
Jˆ4.7 Hz, 4H), 2.69 (m, 2H), 2.59 (t, Jˆ4.7 Hz, 4H), 2.35
(m, 3H), 2.13 (t, Jˆ7.2 Hz, 2H), 1.81±2.04 (m, 4H), 1.15
1
(12H); IR (CH2Cl2) 1740 cm21; 15: H NMR (300 MHz,
CDCl3) d 6.90 (s, 8H), 3.70 (s, 6H), 3.50 (br m, 4H), 3.10
(m, 8H), 2.69 (m, 8H), 2.60 (br, 8H), 2.37 (m, 6H), 1.81±
2.05 (m, 8H), 1.26±1.79 (24H); 13C NMR (75 MHz, CDCl3)
d 175.5, 145.8, 145.3, 118.3, 117.7, 58.8, 53.4 (2C), 51.8,
50.5, 50.1, 40.9, 39.2, 29.4, 29.2, 28.5, 28.4, 27.5, 26.7; IR
1.1.10. Bis[8-[4-[4-(anthraquinone-2-carbonyl)piperazino)-
phenyl)]piperazino]octyl]disul®de (18). To a CH3CN±
H2O (19:1) solution of the 1,10-phenanthroline±HCl±H2O
(34 mg, 0.14 mmol, 2 equiv) was added Ru complex 9
(85 mg, 0.07 mmol). The mixture was degassed for
30 min and irradiated under UV light for 16 h. Basic
alumina (Brockman I) was added to the intense red solution.
After removing the solvent, the alumina residue was dried in
vacuo. This was placed atop a short basic alumina column
and the product was eluted with CHCl3. Any remaining
phenanthroline was then removed by washing the chloro-
form solution with 0.05 M HCl solution and water, then the
organic phase was dried over Na2SO4. Further puri®cation
by TLC (Merck Al2O3 plate) with CHCl3 afforded 18
(16 mg, 35%), identical to the same compound previously
reported by us.8
(CH2Cl2) 1726 cm21
;
FAB HRMS Calcd for M1
(C50H80N6O4S2) 892.5682. Found: 892.5642.
1.1.14. Bis[8-[4-[(4-(4-methoxycarbonylbenzoyl)pipera-
zino)phenyl)]piperazino]octyl] disul®de (17). Compound
16 (27 mg, 0.034 mmol) was stirred with PhHgOAc (38 mg,
0.113 mmol, 3.3 equiv) in CH2Cl2±CH3OH (2 mL, 1:1) at rt
for 6 h. After removing solvent under reduced pressure, the
residue was redissolved in 4 mL CH2Cl2 and purged with
H2S for 2 h. Neutral alumina (Brockman I) was added to the
solution, the solvent was removed by rotary evaporation and
the alumina residue was dried in vacuo. This was placed
atop a short neutral alumina column and the product was
eluted with CHCl3. Further puri®cation by TLC (Merck
Al2O3 plate) with CHCl3 afforded 17 (13 mg, 70%), identi-
cal to the same compound previously reported by us.
1.1.11. Bis[8-[4-[4-(piperidino)phenyl)]piperazino]octyl]
disul®de (13). The procedure is the same as for compound
16. A solution of complex 5 (82 mg, 0.087 mmol) in
CH3CN/NH3(aq) (17 mL/3 mL) was degassed for 30 min
and irradiated under UV light for 48 h to give the product
as a ®lm (crude weight 14 mg, crude yield 41%). Further
puri®cation by TLC (Merck Al2O3 plate) with CHCl3
afforded an analytical sample. 1H NMR (300 MHz,
CDCl3) d 6.89 (s, 8H), 3.13 (br s, 8H), 3.03 (t, Jˆ5.2 Hz,
8H), 2.68 (t, Jˆ7.3 Hz, 4H), 2.63 (br, 8H), 2.40 (t, Jˆ
7.3 Hz, 4H), 1.20±1.80 (m, 36H); 13C NMR (75 MHz,
CDCl3) d 146.6, 145.0, 118.2, 117.7, 58.8, 53.4, 51.9,
50.2, 39.2, 29.5, 29.2 (2C), 28.5, 27.6, 26.8, 26.1, 24.3;
FAB HRMS Calcd for M1 (C46H76N6S2) 776.5573.
Found: 776.5574.
1.2. Deprotection followed by demetallation reactions
1.2.1. Bis[8-[4-[4-(piperidino)phenyl)]piperazino]octyl]
disul®de (13). Deprotection: Complex
5
(163 mg,
0.173 mmol) was stirred with PhHgOAc (192 mg,
0.570 mmol, 3.3 equiv) in CH2Cl2±CH3OH (4 mL, 1:1) at
rt for 7 h. After removing solvent under reduced pressure,
the residue was redissolved in 10 mL CH2Cl2 and purged
with H2S for 3 h. Neutral alumina (Brockman I) was added
to the solution. The solvent was removed by rotary evapo-
ration and the alumina/residue was dried in vacuo. This was
placed atop a short neutral alumina column and the side
product was eluted with CHCl3 then CHCl3±CH3OH
(1:1). The solvent was evaporated and CHCl3 was added.
The organic solution was washed with H2O and dried
over Na2SO4 to give product 19 (111 mg), which was not
puri®ed.
1.1.12. Bis[8-[4-[4-(morpholino)phenyl)]piperazino]octyl]
disul®de (14). The procedure is the same as for compound
16. A solution of complex 6 (145 mg, 0.153 mmol) in
CH3CN/NH3(aq) (17 mL/3 mL) was degassed for 30 min
and irradiated under UV light for 48 h, to give the product
as a ®lm (40 mg, crude yield 67%). Further puri®cation by
TLC (Merck Al2O3 plate) with CHCl3 afforded pure 14. 1H
NMR (300 MHz, CDCl3) d 6.91 (d, Jˆ9.3 Hz, 4H), 6.87 (d,
Jˆ9.3 Hz, 4H), 3.85 (t, Jˆ4.7 Hz, 8H), 3.14 (br, 8H), 3.07
(t, Jˆ4.7 Hz, 8H), 2.68 (t, Jˆ7.2 Hz, 4H), 2.63 (br, 8H),
2.41 (t, Jˆ7.2 Hz, 4H), 1.33±1.68 (24H); 13C NMR
(75 MHz, CDCl3) d 145.6, 145.3, 117.8, 117.3, 67.1, 58.8,
53.4, 50.5, 50.2, 39.2, 29.4, 29.2, 28.5, 27.6, 26.8; FAB
Decomplexation: A solution of complex 19 (111 mg) in
CH3CN-NH3(aq) (17 mL/3 mL) was degassed for 30 min
and then irradiated under UV light for 48 h. Basic alumina
(Brockman I) was added to the solution. The solvent was
removed by rotary evaporation and the alumina residue was
dried in vacuo. This was placed atop a short basic alumina
column and the TAPD derivative was eluted with CHCl3.
Then the procedure was repeated by using silica gel with

A. J. Pearson, J.-J. Hwang / Tetrahedron 57 (2001) 1489±1495
1495
CHCl3 then 4% methanol in chloroform to give the product
13 (12 mg, 18% yield over two steps).
CH3CN±NH3(aq) (17 mL/3 mL) was degassed for 30 min
and irradiated under UV light for 48 h to give the product 15
(20 mg, 41% yield).
1.2.2. Bis[8-[4-[4-(4-methoxycarbonylpiperidino)phenyl)]-
piperazino]octyl] disul®de (15). The procedure is the same
as for conversion of 16 to 17. Compound 12 (105 mg,
0.152 mmol) was stirred with PhHgOAc (169 mg,
0.502 mmol, 3.3 equiv) in CH2Cl2±CH3OH (3 mL, 1:1) at
rt for 10 h. After removing solvent under reduced pressure,
the residue was redissolved in 8 mL CH2Cl2 and purged
with H2S for 3 h to give product 15, isolated in the usual
way as a solid ®lm (33 mg, 48% yield).
Acknowledgements
We are grateful to the National Institutes of Health, General
Medical Sciences, for ®nancial support, and to David
Sopchak and Professor Chung-Chiun Liu for helpful dis-
cussions concerning the electrochemical measurements.
References
1.2.3. Bis[8-[4-[4-(morpholino)phenyl)]piperazino]octyl]
disul®de (14). Deprotection: The procedure is the same as
for compound 19. Complex 6 (205 mg, 0.217 mmol) was
stirred with PhHgOAc (241 mg, 0.716 mmol, 3.3 equiv) in
CH2Cl2±CH3OH (4 mL, 1:1) at rt for 7 h. After removing
solvent under reduced pressure, the residue was redissolved
in 14 mL CH2Cl2 and purged with H2S for 3 h to give
product 20 (150 mg).
1. Wurster, C.; Sendtner, R. Ber. Dtsch. Chem. Ges. 1879, 12,
1803.
2. Foster, R. Organic Charge Transfer Complexes, Academic
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Decomplexation: The procedure is the same as for
compound 13. A solution of complex 20 (150 mg) in
CH3CN/NH3 (17 mL/3 mL) was degassed for 30 min and
irradiated under UV light for 48 h to give the product 14
(20 mg, 24% yield over two steps).
1.2.4. Bis[8-[4-[h6-4-(4-methoxycarbonylpiperidino)pi-
perazino)phenyl)(h5-cyclo-pentadienyl)ruthenium(II)]-
piperazino]octyl] disul®de hexa¯uorophosphate (21).
The procedure is the same as for compound 19. Complex
7 (218 mg, 0.218 mmol) was stirred with PhHgOAc
(260 mg, 0.772 mmol, 3.5 equiv) in CH2Cl2±CH3OH
(4 mL, 1:1) at rt for 7 h. After removing solvent under
reduced pressure, the residue was redissolved in 10 mL
CH2Cl2 and purged with H2S for 3 h to give product 21
(130 mg, 79%).1H NMR (300 MHz, CDCl3) d 5.73 (s,
8H), 5.19 (s, 10H), 3.63 (s, 6H), 3.50 (br m, 4H), 2.91 (br,
8H), 2.42±2.61 (18H), 2.29 (t, Jˆ7.1 Hz, 4H), 1.81±2.02
(m, 8H), 1.23±1.60 (24H); 13C NMR (75 MHz, CDCl3) d
174.6, 122.5, 121.7, 77.4, 67.7, 67.4, 58.4, 52.0, 51.9,
47.7, 47.0, 39.8, 39.1, 33.9, 29.4, 29.1, 29.0, 27.4, 26.6,
26.4; IR (CHCl3) 1741 cm21; FAB HRMS Calcd for
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5123.
7. Fossum, D.; Fox, M. A.; Gelormini, A. M.; Pearson, A. J.
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14. (a) Lichtenberger, D. L.; Johnston, R. L.; Hinkelmann, K.;
Suzuki, T.; Wudl, F. J. Am. Chem. Soc. 1990, 112, 3302.
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Commun. 1999, 1493. (c) Yip, C. M.; Ward, M. D. Langmuir
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M±PF6 (C60H90N6O4S2Ru2PF6, 102Ru) 1371.4200. Found:
2
1371.4191. This complex was converted to 15 as described
above: A solution of complex 21 (80 mg, 0.053 mmol) in