Substituted 1,10-phenanthroline-5,6-diamines and their extension to soluble, acetylenic pyrazinophenanthrolines

Article abstract of DOI:10.1055/s-2005-916010

2,9-Disubstituted and 3,8-disubstituted 1,10-phenanthrolines have been converted to the respective 5,6-diamines in three steps. The new heterocycles have been employed in condensation reactions with a protected 1,2-dialkynyl-1,2-dione to afford solubility-improved, acetylenic pyrazinophenanthrolines (pyzphen). In an initial study, the synthetic scope of these novel acetylenic ligands is evaluated. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-916010

PAPER
3135
Substituted 1,10-Phenanthroline-5,6-diamines and their Extension to Soluble,
Acetylenic Pyrazinophenanthrolines
Soluble,
A
cety
a
lenic
P
yra
z
s
inophenan
c
throlines ha Ott,*1 Rüdiger Faust2
Christopher-Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
Fax +46(18)4713818; E-mail: sascha.ott@fki.uu.se
Received 16 February 2005; revised 1 June 2005
phenomena, chemical transformations on extended planar
Abstract: 2,9-Disubstituted and 3,8-disubstituted 1,10-phenan-
p-systems are generally difficult to be carried out.8
throlines have been converted to the respective 5,6-diamines in
three steps. The new heterocycles have been employed in conden-
sation reactions with a protected 1,2-dialkynyl-1,2-dione to afford
solubility-improved, acetylenic pyrazinophenanthrolines (pyz-
phen). In an initial study, the synthetic scope of these novel acety-
lenic ligands is evaluated.
Complexations to metal fragments have frequently been
used to increase the solubility of the otherwise sparingly
soluble ligands.8 However, this strategy constitutes not
only a limitation to the design, but also prevents an evalu-
ation of the (photo)physical properties of the chelating
heterocycle itself. An alternative approach has been the
introduction of bulky solubilizing substituents to prevent
the heterocycles from p-stacking. This very successful
strategy has been employed to increase the solubility of
monomeric9,10 as well as oligomeric phen derivatives.11
However, solubility limitations are an even greater issue
in systems with a higher degree of aromatic ring annula-
tion such as pyzphen or dppz. We thus decided to adopt
the strategy which has been found viable for the solubili-
zation of phen and to exploit it for the preparation of sol-
uble pyzphen heterocycles. In our earlier work we have
experienced that a terminally unprotected, diacetylenic
pyzphen is literally insoluble in any organic solvent.12
This compound is thus a good reference to study the solu-
bilizing properties of newly introduced substituents and
we embarked on the synthesis of acetylenic pyzphen het-
erocycles bearing bulky alkyl or aryl substituents. Soluble
acetylenic pyzphen may open new pathways for further
functionalization of the acetylene or the construction of
highly unsaturated carbon scaffolds with annulated metal
binding sites.13
Key words: acetylenes, condensation, ligands, solubility, synthesis
Aromatic N-heterocycles of the 1,10-phenanthroline type
(phen) have been used extensively as chelating agents for
transition metals, in particular for the bis(bipyridyl)ruthe-
nium(II) fragment.3 Extended N-heterocyclic aromatic
ligands such as pyrazinophenanthrolines (pyzphen) or
dipyridophenazines (dppz) feature lower p* orbitals and,
hence, are better electron acceptors than the phen moiety
itself (Figure 1).4
N
N
N
N
N
N
N
N
N
N
pyzphen
phen
dppz
Figure 1
In ruthenium(II) complexes of pyzphen and dppz, the
light-induced charge-separated state is directed towards
these ligands. The complexes have thus found applica-
tions as luminescent probes of many aprotic microenvi-
ronments, including those of polymer films, micelles and
of DNA.3–5 More recently, dinuclear complexes of ruthe-
nium with extended N-heterocyclic bridging ligands were
demonstrated to be multi-electron acceptors and up to four
electrons could be accumulated in a system having two
dppz units fused back-to-back.6 The ability to store four
electrons is a vital aspect for the oxidation of water in nat-
ural and artificial photosynthesis.7 Despite these appeal-
ing prospects, the variety of bridging ligands where the
phen coordination sites are fused by a number of benzan-
nulated rings is limited, a fact that is caused in great part
by the compounds’ low solubilities. Due to aggregation
As pyzphens can be derived from the condensation of
phen-5,6-diamines with suitable 1,2-diketones, it seemed
desirable to have the substituents on equivalent positions
around the phen core to avoid complex spectroscopic da-
ta. Introduction of substituents in the a positions of phen
can be achieved in a Ziegler reaction.14
Following the general protocol, butyl lithium and 4-tert-
butylphenyl lithium15 were reacted separately with dry
phen, resulting in the addition of the organolithium re-
agent to both pyridine subunits of phen. Subsequent hy-
drolysis and dehydrogenation of the intermediate with
manganese(IV) oxide affords the 2,9-disubstituted phen
analogues in 62% and 51% yield, respectively
(Scheme 1).
Substitution of phen in the b positions was found to be
more difficult and required a multi-step sequence. Only a
few examples in the literature address the synthesis of
these compounds,10 one of which describes the synthesis
of 3,8-dibutyl-4,7-dichloro-phen in four steps on a gram-
SYNTHESIS 2005, No. 18, pp 3135–3139
x
x.
x
x
.
2
0
0
5
Advanced online publication: 26.08.2005
DOI: 10.1055/s-2005-916010; Art ID: T01905SS
© Georg Thieme Verlag Stuttgart · New York

3136
S. Ott, R. Faust
PAPER
Rβ
Rβ
Rβ
Rβ
Rβ
Rα
Cl
Cl
Rα
Rα
ii
Rα
iii
N
N
N
N
N
N
N
N
N
O
O
N
N
N
N
OH
OH
N
N
NH2
NH2
ii
i
i
1a–c
quant.
N
Rα
Rα
Rα
Rα
Rβ
Rβ
Rβ
Rβ
Rβ
1a Rα = n-Bu
1b Rα
, 62%
, 51%
2a: 95%
2c: 74%
3a: 64%
3c: 72%
4a: 55%
4c: 58%
1c Rβ = n-Bu
=
Scheme 2 Reagents and conditions: (i) KBr, concd HNO3, concd
H2SO4, D, 2 h, 95% for 2a, 74% for 2c. (ii) NH2OH·HCl, BaCO3,
EtOH, D, 16 h, 64% for 3a, 72% for 3c. (iii) hydrazine, Pd/C, EtOH,
D, 16 h, 55% for 4a, 58% for 4c.
Scheme 1 Reagents and conditions: (i) 1) Ra-Li, toluene, 16 h, r.t.;
2) H2O; 3) MnO2, 62% for 1a, 51% for 1b. (ii) Zinc, AcOH, D, 3 d,
quant.
scale.9 For our purposes, removal of the chloro function-
alities in this compound was necessary since heavy atoms
such as chlorine are known to quench luminescence and
would thus interfere with the photophysical properties of
the pyzphen heterocycle and its corresponding metal com-
plex. After some initial ill-fated attempts such as hydro-
genolysis of the chloropyridine with palladium on carbon
in acetic acid,16 it was found that refluxing the 4,7-dichlo-
ro-phen in acetic acid in the presence of zinc afforded
dechlorinated 1c in quantitative yield (Scheme 1).17 Al-
though some difficulties were expected in purifying the
product from residual zinc salts, the NMR data for 1c iso-
lated from this experiment were identical to the reported
values10f and 1c was used for the subsequent reactions
without further purification.
possible hydrogen bonding phenomena between the
oxime groups. However, the identity of the compounds
could be unambiguously established by mass spectrome-
try and IR spectrophotometry.
Reduction of the dibutyl-substituted dioximes 3a,c pro-
ceeded smoothly by refluxing a solution of the dioximes
in ethanol over night in the presence of hydrazine and
10% palladium on carbon. After removal of the palladium
catalyst by filtration through Celite, the phen-5,6-di-
amines 4a,c were isolated as dark brown solids. The solu-
bilizing effect of the two butyl substituents became
apparent again as the phen-5,6-diamines 4a,c were found
to dissolve readily in polar organic solvents. This fact not
only facilitates the acquisition of NMR data, but is also an
encouraging prospect with regard to the solubility behav-
ior of the targeted pyzphen heterocycles.
With a number of substituted phen derivatives in hand,
their transformation to substituted pyzphens was ex-
plored. Hence, 1a–c were heated separately to reflux in a
mixture of concentrated sulfuric and nitric acid in the
presence of potassium bromide for two hours.18 After
workup, the butyl-substituted phen-5,6-diones 2a and 2c
could be isolated as yellow solids in 95% and 74% yield,
respectively (Scheme 2). Both compounds were found to
be considerably more soluble than the parent 1,10-
phenanthroline-5,6-dione18 and could be characterized by
NMR spectroscopy. In contrast, no oxidation product of
the aryl-substituted phen 1b could be detected. Presum-
ably, phen 1b decomposes in undesired electrophilic sub-
stitution side reactions on the aryl termini promoted by the
rather harsh reaction conditions.
To elaborate 4a,c to terminally free, acetylenic pyzphen
ligands, they were condensed with the (i-Pr)3Si-terminat-
ed hexa-1,5-diyne-3,4-dione20 in refluxing toluene in the
presence of molecular sieves to obtain 5a and in acetic
acid to afford 5c. The pyzphens 5a,c were obtained in
modest to good yields after chromatographic purification
on silica (Scheme 3). Subsequent treatment of 5a,c with
tetrabutylammonium fluoride (TBAF) in wet THF result-
ed in the removal of the silyl protecting groups, liberating
the terminal 2,3-diacetylenic pyzphens 6a,c.
Much to our satisfaction, dibutyl-substituted 6a and 6c,
unlike their non-butylated counterparts, were found to ex-
hibit good solubility in most organic solvents. The butyl
substituents, attached either in the a or in the b positions
to the phen nitrogens impose a sufficient steric bulk to
prevent the pyzphen core from p-stacking. Having ob-
tained a soluble pyzphen ligand with two terminally free
acetylene units for the first time, we set out to explore its
chemistry. In an initial study, a solution of 6c in methanol
and pyridine was exposed to the copper-mediated acety-
lene cross-coupling conditions developed by Eglinton.21
The outcome of this experiment was quite unexpected.
After washing the crude reaction mixture with aqueous
cyanide to remove the copper from the phen binding site,
and purification of the residual material by column chro-
matography, no butadiynyl-linked product but rather the
bis-enolether 7c was isolated in modest yield. The product
The two successfully prepared butyl-substituted phen-di-
ones 2a and 2c could be further elaborated to the corre-
sponding dioximes by refluxing the diones together with
hydroxylamine hydrochloride and barium carbonate in
ethanol over night.19 In analogy to the alkylated phen-5,6-
diones, the substituted dibutyl-phen-5,6-dioximes 3a,c
show an improved solubility compared to that of the non-
substituted parent phen-5,6-dioxime. This effect also fa-
cilitates the isolation procedure during which the barium
salts can easily be removed by an aqueous work-up. The
NMR spectra obtained for the dibutyl-phen-5,6-dioximes
were found to be rather convoluted due to the presence of
cis/trans isomers around the imine functionalities and
Synthesis 2005, No. 18, 3135–3139 © Thieme Stuttgart · New York

PAPER
Soluble, Acetylenic Pyrazinophenanthrolines
3137
3,8-Dibutyl-1,10-phenanthroline (1c)
Rβ
i
Zinc powder (5.2 g, 7.95 mmol) was added to a solution of 3,8-dibu-
tyl-4,7-dichloro-1,10-phenanthroline (1.47 g, 4.07 mmol) in wet
AcOH (40 mL). After refluxing for 3 d, the reaction mixture was
poured onto ice (50 g) before CHCl3 (50 mL) was added. After ad-
justing the pH to 14 by the addition of 10 M aq NaOH, the layers
were separated. The aqueous layer was extracted with CHCl3
(2 × 50 mL) and the combined extracts were dried (Na2SO4), fil-
tered and concentrated in vacuo.
4a
Rα
R
N
N
N
N
O
R
R
O
R
Rα
4c
5a: 54%
5c: 77%
R = Si(i-Pr)3
ii
Rβ
Yield: 1.19 g (4.07 mmol, quant.). The spectroscopic data are in
agreement with the reported values.10f
1H NMR (400 MHz, CDCl3): d = 8.98 (d, J = 2.2 Hz, 2 H, a CH),
7.96 (d, J = 2.2 Hz, 2 H, g CH), 7.69 (s, 2 H, phen), 2.84 (t, J = 7.6
Hz, 4 H, CH2), 1.72 (m, 4 H, CH2), 1.40 (m, 4 H, CH2), 0.95 (t,
J = 7.3 Hz, 6 H, CH3).
Rβ
Rβ
Rα
H
H
OCH3
OCH3
N
N
N
N
iii
N
N
iv
N
N
13C NMR (100 MHz, CDCl3): d = 151.4, 144.6, 137.2, 134.4, 128.0,
126.3 (all aromatic C), 33.3, 32.8, 22.3, 13.9 (Bu).
Rα
7c: 40%
6a: 89%
6c: 77%
Rβ
Rβ
2,9-Dibutyl-1,10-phenanthroline-5,6-dione (2a)
Scheme 3 Reagents and conditions: (i) Molecular sieves, toluene,
D, 2 h, 54% for 5a. (ii) AcOH, r.t., 1 h, 77% for 5c. (iii) TBAF, wet
THF, 0 °C, 5 min, 89% for 6a, 77% for 6c. (iv) 1) CuCl, pyridine, Me-
OH, 30 min; 2) Cu(OAc)2, 40 °C, 3 h; 3) aq KCN, sonication, 40%.
2,9-Dibutylphenanthroline (1.46 g, 5.00 mmol) and KBr (5.95 g, 50
mmol) were placed in an ice-cooled one-neck flask and ice-cooled
concd H2SO4 (20 mL) was added carefully along the wall of the
flask. Concd HNO3 (10 mL) was added and the fuming reaction
mixture was refluxed for 2 h. After cooling to r.t., the red solution
was poured onto ice-cold H2O (400 mL) and neutralized by careful
addition of NaHCO3. The yellow solution was extracted with
CH2Cl2 (5 × 70 mL), the combined organic layers were washed with
brine (100 mL), dried (Na2SO4), filtered and concentrated in vacuo.
possesses trans configuration across both double bonds as
demonstrated by the coupling constant of 12.1 Hz be-
tween the two magnetically inequivalent alkene protons.
Apparently, the ynimine moieties of the ethynylpyrazine
unit in pyzphens of type 6 constitute Michael acceptors
and as such are prone to nucleophilic attack on the b car-
bon of the acetylene. Presumably, the temporary coordi-
nation of the copper cation to the phen binding site further
increases the electrophilicity of these carbon centers.
Yellow solid; yield: 1.53 g (4.75 mmol, 95%); mp 86 °C.
IR (KBr): 3066 (CH), 2957 (CH), 1692 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 8.34 (d, J = 8.0 Hz, 2 H, g CH),
7.37 (d, J = 8.0, 2 H, b CH), 3.06 (t, J = 8.0 Hz, 4 H, CH2), 1.83 (m,
4 H, CH2), 1.46 (m, 4 H, CH2), 0.97 (t, J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 179.1 (C=O), 171.0, 152.7,
137.3, 126.1, 124.4 (all aromatic C), 39.0, 31.2, 22.6, 13.9 (aliphatic
C).
In conclusion, the successful realization of soluble acety-
lenic pyzphens, combined with the nucleophilic proper-
ties of the two ynimine subunits, open the way to a new
chemistry based on these structural motives. Synthetic
work along these lines is currently in progress.
3,8-Dibutyl-1,10-phenanthroline-5,6-dione (2c)
Synthesized from 3,8-dibutyl-1,10-phenanthroline (1.19 g, 4.07
mmol) in a procedure similar to the one used for the preparation of
2a.
All reactions were conducted in oven-dried glassware under an ar-
gon atmosphere. Unless otherwise indicated, all reagents were pur-
chased from commercial suppliers and were used without further
purification. 2,9-Disubstituted-1,10-phenanthrolines 1a,b,14 3,8-
dibutyl-4,7-dichloro-1,10-phenanthroline9 and 1,6-bis(triisopropyl-
silyl)hexa-1,5-diyne-3,4-dione20 were prepared according to the lit-
erature procedures. All compounds presented herein were pure by
NMR analysis. Due to the hygroscopic nature of the phen-based de-
rivatives, further characterization of key compounds was performed
by high-resolution mass spectrometry (HRMS) rather than by ele-
mental analysis. Flash column chromatography was performed un-
der positive pressure from a compressed air line using either silica
60 (supplied by BDH: 230–400 mesh) or neutral Al2O3 (Fluka).
Melting points were determined on a Reichert hotstage apparatus
and are uncorrected. NMR spectra were recorded on a Bruker
AMX400 machine in CDCl3 or DMSO-d6. The chemical shift is
given in units of d relative to the resonances of the residual protic
solvent. IR spectra were recorded on a Perkin Elmer 1600 FT-IR in-
strument either as KBr discs, or in CH2Cl2 solution. UV spectra
were taken on a Perkin Elmer Lambda 40 instrument. Extinction co-
efficients e are given in units of M–1·cm–1. Mass spectra were re-
corded on a VG ZAB SE machine (EI and FAB ionization).
Microanalyses were carried out on a Perkin Elmer 2400 CHN ma-
chine.
Yellow solid; yield: 970 mg (3.00 mmol, 74%); mp 140 °C (dec.).
IR (CH2Cl2): 2956 (CH), 2930 (CH), 2860 (CH), 1687 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 8.82 (d, J = 2.2 Hz, 2 H, a CH),
8.20 (d, J = 2.2 Hz, 2 H, g CH), 2.71 (t, J = 7.8 Hz, 4 H, CH2), 1.63
(m, 4 H, CH2), 1.35 (m, 4 H, CH2), 0.90 (t, J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 179.1 (C=O), 156.6, 150.8,
140.5, 136.4, 127.2 (all aromatic C), 32.6, 32.3, 22.1, 13.7 (Bu).
MS (FAB): m/z (%) = 323 (100) [M+ + H].
2,9-Dibutyl-1,10-phenanthroline-5,6-dioxime (3a)
A suspension of 2a (644 mg, 2.00 mmol), hydroxylamine hydro-
chloride (486 mg, 7 mmol) and BaCO3 (592 mg, 3.00 mmol) in
EtOH (30 mL) was heated to reflux for 12 h. After removal of the
solvent, the residue was triturated with 0.2 M HCl (40 mL) for 1 h.
The suspension was extracted with CH2Cl2 (3 × 50 mL) and the
combined extracts were washed with brine (30 mL), dried
(Na2SO4), filtered and concentrated in vacuo.
Yield: 450 mg (1.28 mmol, 64%); mp 145 °C.
IR (KBr): 2957 (CH), 2866 (CH), 1583 cm–1 (C=NOH).
MS (FAB): m/z (%) = 352 (100) [M+].
Synthesis 2005, No. 18, 3135–3139 © Thieme Stuttgart · New York

3138
S. Ott, R. Faust
PAPER
3,8-Dibutyl-1,10-phenanthroline-5,6-dioxime (3c)
Synthesized from 2c (969 mg, 3.00 mmol) in a procedure similar to
the one used for the preparation of 3a.
CH2), 1.50 (m, 4 H, CH2), 1.20 (m, 42 H, i-Pr), 0.90 (t, J = 7.4 Hz,
6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 166.0, 147.2, 139.3, 138.0, 133.8,
124.3, 123.2 (all aromatic C), 103.7, 99.3 (C≡C), 39.1, 31.7, 22.8
(aliphatic C), 18.7 [CH(CH3)2], 14.0 (aliphatic C), 11.3 (Si–C).
HRMS (FAB): m/z [M+ + H] calcd for C44H65N4Si2: 705.4748;
found: 705.4776.
Yield: 765 mg (2.17 mmol, 72%); mp 158 °C.
IR (KBr): 2956 (CH), 2929 (CH), 2859 (CH), 1560 cm–1 (C=NOH).
MS (FAB): m/z (%) = 353 (100) [M+ + H], 335 (87) [M+ + H –
H2O].
UV (CH2Cl2): lmax (e) = 282 (60000), 319 (24000), 389 nm
(23000).
HRMS (FAB): m/z [M+ + H] calcd for C20H25N4O2: 353.1978;
found: 353.1960.
6,11-Dibutyl-2,3-bis[(triisopropylsilyl)ethynyl]pyrazino-[2,3-f]-
1,10-phenanthroline (5c)
2,9-Dibutyl-1,10-phenanthroline-5,6-diamine (4a)
A suspension of 3a (352 mg, 1.00 mmol) and palladium on charcoal
(10%, 300 mg) in anhyd EtOH (50 mL) was purged with argon for
15 min and heated to reflux. A solution of hydrazine-monohydrate
(1.75 mL, 36.00 mmol) in anhyd EtOH (15 mL) was added over a
period of 30 min. After refluxing for 16 h the hot reaction mixture
was filtered through a pad of Celite and washed with boiling EtOH
(4 × 15 mL). After removal of the solvent in vacuo the remaining
black residue was triturated with H2O (15 mL), stored at 4 °C for 2
h and collected.
Compound 4c (97 mg, 0.30 mmol) was added in one portion to a
deoxygenated solution of 1,6-bis(triisopropylsilyl)hexa-1,5-diyne-
3,4-dione (126 mg, 0.30 mmol) in glacial AcOH (10 mL). After stir-
ring for 1 h, the solvent was removed at high vacuum and the re-
maining red residue was purified by column chromatography
(silica, 5% MeOH in CH2Cl2) and recrystallized from MeOH, white
solid.
Yield: 164 mg (0.23 mmol, 77%); mp 60 °C.
Yield: 177 mg (0.55 mmol, 55%); mp 188 °C.
IR (KBr): 3355 (NH), 3228 (NH), 2956 (CH), 2928 cm–1 (CH).
1H NMR (400 MHz, DMSO-d6): d = 8.40 (d, J = 8.7 Hz, 2 H, g
CH), 7.49 (d, J = 8.7 Hz, 2 H, b CH), 2.94 (t, J = 7.9 Hz, 4 H, CH2),
1.71 (m, 4 H, CH2), 1.37 (m, 4 H, CH2), 0.90 (t, J = 7.3 Hz, 6 H,
CH3).
13C NMR (100 MHz, DMSO-d6): d = 156.7, 139.1, 129.7, 121.8,
121.6, 121.1 (all aromatic C), 37.4, 31.8, 22.2, 13.9 (aliphatic C).
MS (FAB): m/z (%) = 323 (100) [M+ + H].
HRMS (FAB): m/z [M+ + H] calcd for C20H27N4: 323.2236; found
IR (KBr): 2941 (CH), 2891 (CH), 2158 cm–1 (C≡C).
1H NMR (400 MHz, CDCl3): d = 9.12 (d, J = 2.2 Hz, 2 H, g CH),
8.99 (d, J = 2.2 Hz, 2 H, a CH), 2.89 (t, J = 7.6 Hz, 4 H, CH2), 1.73
(m, 4 H, CH2), 1.40 (m, 4 H, CH2), 1.18 (m, 42 H, i-Pr), 0.98 (t,
J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 153.3, 145.8, 139.4, 138.4, 138.2,
132.3, 125.4 (all aromatic C), 103.6, 99.9 (both C≡C), 33.1, 32.8,
22.2 (all Bu), 18.7 [CH(CH3)2], 13.8 (Bu), 11.0 (CH).
MS (EI): m/z (%) = 705 (38) [M+], 661 (65) [M+ – i-Pr], 619 [M+ –
2 i-Pr].
HRMS (FAB): m/z [M + H]+ calcd for C44H65N4Si2: 705.4748;
323.2234.
found 705.4730.
3,8-Dibutyl-1,10-phenanthroline-5,6-diamine (4c)
UV (CH2Cl2): lmax (e) = 280 (60000), 317 (27000), 359 (12000),
367 (16000), 378 (15000), 386 nm (22000).
Synthesized from 3c (352 mg, 1.00 mmol) in a procedure similar to
the one used for the preparation of 4a.
Anal. Calcd for C44H64N4Si2·0.5H2O: C, 74.0; H, 9.1; N, 7.8. Found:
C, 74.1; H, 9.0; N, 7.9.
Yield: 188 mg (0.58 mmol, 58%); mp 156 °C.
IR (KBr): 2956 (CH), 2927 (CH), 2858 cm–1 (CH).
1H NMR (400 MHz, DMSO-d6): d = 8.59 (d, J = 2.2 Hz, 2 H, a
CH), 8.24 (d, J = 2.2 Hz, 2 H, g CH), 5.13 (br s, 4 H, NH2), 2.79 (t,
J = 7.9 Hz, 4 H, CH2), 1.70 (m, 4 H, CH2), 1.37 (m, 4 H, CH2), 0.97
(t, J = 7.3 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 145.8, 139.4, 135.5, 127.1, 122.1,
121.8 (all aromatic C), 33.0, 32.4, 21.9, 13.8 (Bu).
HRMS (FAB): m/z [M+ + H] calcd for C20H27N4: 323.2236; found:
323.2250.
7,10-Dibutyl-2,3-diethynylpyrazino[2,3-f]-1,10-phenanthroline
(6a)
Tetrabutylammonium fluoride (1.5 mL, 1.5 mmol, 1 M soln in
THF) was added to a degassed solution of compound 5a (352 mg,
0.50 mmol) in wet THF (20 mL) at 0 °C. After stirring for 5 min the
reaction was quenched by the addition of a sat. aq solution of NH4Cl
(20 mL). The layers were separated and the aqueous layer was ex-
tracted with CH2Cl2 (3 × 30 mL). The combined organic extracts
were washed with brine (30 mL) and dried (Na2SO4). Purification
by column chromatography (alumina, 10% EtOAc in hexane),
white solid.
7,10-Dibutyl-2,3-bis[(triisopropylsilyl)ethynyl]pyrazino [2,3-f]-
1,10-phenanthroline (5a)
Yield: 174 mg (0.44 mmol, 89%); mp 137 °C.
To a solution of 4a (161 mg, 0.50 mmol) in toluene (15 mL) over
activated molecular sieves was added a solution of 1,6-bis(triisopro-
pylsilyl)hexa-1,5-diyne-3,4-dione (210 mg, 0.50 mmol) in toluene
(10 mL) and the reaction was stirred at 100 °C for 2 h. After remov-
al of the molecular sieves, the solvent was removed in vacuo to af-
ford a brown solid which was subjected to column chromatography
(alumina, 20% EtOAc in hexane) to furnish a hygroscopic, off-
white solid.
IR (CH2Cl2): 2961 (CH), 2931 (CH), 2117 cm–1 (C≡C).
1H NMR (400 MHz, CDCl3): d = 9.32 (d, J = 8.3 Hz, 2 H, g CH),
7.63 (d, J = 8.3 Hz, 2 H, b CH), 3.64 (s, 2 H, acetylenic H), 3.21 (m,
4 H, CH2), 1.91 (m, 4 H, CH2), 1.50 (m, 4 H, CH2), 0.96 (t, J = 7.4
Hz, 6 H, CH3).
13C NMR (CDCl3, 100 MHz): d = 166.6, 147.3, 139.2, 138.6, 133.8,
123.9, 123.4 (all aromatic C), 83.8, 80.2 (C≡C), 39.1, 31.7, 22.8,
14.0 (aliphatic C).
Yield: 190 mg (0.27 mmol, 54%); mp 74 °C.
IR (CH2Cl2): 2962 (CH), 2945 (CH), 2151 cm–1 (C≡C).
1H NMR (400 MHz, CDCl3): d = 9.32 (d, J = 8.3 Hz, 2 H, g CH),
7.62 (d, J = 8.3 Hz, 2 H, b CH), 3.21 (m, 4 H, CH2), 1.92 (m, 4 H,
HRMS (FAB): m/z [M + H]+ calcd for C26H25N4: 393.2079; found
393.2062.
UV (CH2Cl2): lmax (e) = 275 (53000), 381 nm (19000).
Synthesis 2005, No. 18, 3135–3139 © Thieme Stuttgart · New York

PAPER
Soluble, Acetylenic Pyrazinophenanthrolines
3139
6,11-Dibutyl-2,3-diethynylpyrazino[2,3-f]-1,10-phenanthroline
(6c)
Synthesized from 5c (176 mg, 0.25 mmol) in a procedure similar to
the one used for the preparation of 6a. Purification by column chro-
matography (silica, 3% MeOH in CH2Cl2), white solid.
Heinrich-Plett-Str. 40, 34132 Kassel, Germany, Fax:
+49(561)8044752, E-Mail: R.Faust@Uni-Kassel.de.
(3) For recent examples see: (a) Olson, E. J. C.; Hu, D.;
Hörmann, A.; Jonkman, A. M.; Arkin, M. R.; Stemp, E. D.
A.; Barton, J. K.; Barbara, P. F. J. Am. Chem. Soc. 1997, 119,
11458. (b) Brennaman, M. K.; Meyer, T. J.; Papanikolas, J.
M. J. Phys. Chem. A 2004, 108, 9938. (c) Aldrich-Wright,
J.; Brodie, C.; Glazer, E. C.; Luedtke, N. W.; Elson-Schwab,
L.; Tor, Y. Chem. Commun. 2004, 1018. (d) Rezvani, A.;
Bazzi, H. S.; Chen, B.; Rakotondradany, F.; Sleiman, H. F.
Inorg. Chem. 2004, 43, 5112.
Yield: 76 mg (0.19 mmol, 77%); mp 160 °C.
IR (KBr): 3221 (C≡CH), 2954 (CH), 2927 (CH), 2859 (CH), 2104
cm–1 (C≡C).
1H NMR (400 MHz, CDCl3): d = 9.13 (d, J = 2.2 Hz, 2 H, g CH),
9.03 (d, J = 2.2 Hz, 2 H, a CH), 3.65 (s, 2 H, C≡CH), 2.88 (t, J = 7.9
Hz, 4 H, CH2), 1.74 (m, 4 H, CH2), 1.41 (m, 4 H, CH2), 0.94 (t,
J = 7.3 Hz, 6 H, CH3)
13C NMR (CDCl3, 100 MHz): d = 153.8, 146.0, 139.4, 138.9, 138.8,
132.3, 125.1 (all aromatic C), 84.1, 80.0 (both C≡C), 33.4, 33.0,
22.3, 13.8 (all Bu).
(4) Delaney, S.; Pascaly, M.; Bhattacharya, P. K.; Han, K.;
Barton, J. K. Inorg. Chem. 2002, 41, 1966.
(5) Guo, X.-Q.; Castellano, F. N.; Li, L.; Lakowicz, J. R.
Biophys. Chem. 1998, 71, 51.
(6) (a) Konduri, R.; Ye, H.; MacDonnell, F. M.; Serroni, S.;
Campagna, S.; Rajeshwar, K. Angew. Chem. Int. Ed. 2002,
41, 3185. (b) Chiorboli, C.; Rodgers, M. A. J.; Scandola, F.
J. Am. Chem. Soc. 2003, 125, 483. (c) Konduri, R.;
Tacconi, N. R. D.; Rajeshwar, K.; MacDonnell, F. M. J. Am.
Chem. Soc. 2004, 126, 11621.
(7) Sun, L.; Hammarström, L.; Åkermark, B.; Styring, S. Chem.
Soc. Rev. 2001, 30, 36.
(8) Ishow, E.; Gourdon, A.; Launay, J.-P.; Chiorboli, C.;
Scandola, F. Inorg. Chem. 1999, 38, 1504.
(9) (a) Schmittel, M.; Ammon, H. Synlett 1997, 1096.
(b) Schmittel, M.; Ammon, H. Eur. J. Org. Chem. 1998, 785.
(10) (a) Ziessel, R.; Stroh, C. Tetrahedron Lett. 2004, 45, 4051.
(b) Loren, J. C.; Siegel, J. S. Angew. Chem. Int. Ed. 2001, 40,
754. (c) Joshi, H. S.; Jamshidi, R.; Tor, Y. Angew. Chem. Int.
Ed. 1999, 38, 2721. (d) Toyota, S.; Woods, C. R.; Benaglia,
M.; Siegel, J. S. Tetrahedron Lett. 1998, 39, 2697.
(e) Connors, P. J.; Tzalis, D.; Dunnick, A. L.; Tor, Y. Inorg.
Chem. 1998, 37, 1121. (f) Belser, P.; Bernhard, S.; Guerig,
U. Tetrahedron 1996, 52, 2937.
HRMS (FAB): m/z [M + Na]+ calcd for C26H24N4Na: 415.1899;
found: 415.1904.
UV (CH2Cl2): lmax (e) = 274 (52000), 319 (23000), 351 (11000),
359 (13000), 369 (10000), 377 nm (15000).
6,11-Dibutyl-2,3-bis[(E)-2-methoxyvinyl]pyrazino[2,3-f]-1,10-
phenanthroline (7c)
CuCl (85 mg, 0.86 mmol) was added to a degassed solution of 6c
(48 mg, 0.12 mmol) in MeOH and pyridine (1:1, 100 mL) and
Cu(OAc)2·H2O (171 mg, 0.86 mmol) was added at 40 °C. After 3 h
at this temperature, a degassed solution of KCN (1.1 g, 16.90 mmol)
in H2O (5 mL) was added. Sonication for 1 h was followed by re-
moval of the solvents in vacuo. The residue was filtered through a
plug of silica (eluent: 10% MeOH in CH2Cl2) and further purified
by column chromatography (silica, 4% MeOH in CH2Cl2).
Yield: 22 mg (0.05 mmol, 40%); mp 94 °C.
IR (CH2Cl2): 2961 (CH), 2932 (CH), 2860 (CH), 1626 cm–1 (C=C).
(11) For recent examples see: (a) Schmittel, M.; Michel, C.;
Wiegrefe, A. Synthesis 2005, 367. (b) Kalsani, V.; Ammon,
H.; Jackel, F.; Rabe, J. P.; Schmittel, M. Chem. Eur. J. 2004,
5481. (c) Schmittel, M.; Kalsani, V.; Fenske, D.; Wiegrefe,
A. Chem. Commun. 2004, 490. (d) Schmittel, M.; Ammon,
H.; Kalsani, V.; Wiegrefe, A.; Michel, C. Chem. Commun.
2002, 2566. (e) Grave, C.; Schlüter, A. D. Eur. J. Org.
Chem. 2002, 3075. (f) Schmittel, M.; Michel, C.; Wiegrefe,
A.; Kalsani, V. Synthesis 2001, 1561. (g) Schmittel, M.;
Ammon, H. Synlett 1999, 750.
(12) Faust, R.; Ott, S. J. Chem. Soc., Dalton Trans. 2002, 1946.
(13) Ott, S.; Faust, R. Chem. Commun. 2004, 388.
(14) Dietrich-Buchecker, C. O.; Marnot, P. A.; Sauvage, J.-P.
Tetrahedron Lett. 1982, 50, 5291.
1H NMR (400 MHz, CDCl3): d = 9.10 (d, J = 2.0 Hz, 2 H, g CH),
8.99 (d, J = 2.0 Hz, 2 H, a CH), 8.03 (d, J = 12.1 Hz, 2 H, HC=C),
6.18 (d, J = 12.1 Hz, 2 H, C=CH), 3.89 (s, 6 H, OCH3), 2.91 (t,
J = 7.7 Hz, 4 H, CH2), 1.77 (m, 4 H, CH2), 1.44 (m, 4 H, CH2), 0.97
(t, J = 7.4 Hz, 6 H, CH3).
13C NMR (100 MHz, CDCl3): d = 156.9, 152.1, 147.2, 145.2, 137.9,
136.9, 131.2 (all aromatic C), 126.6, 99.9 (C=C), 57.6 (OCH3),
33.5, 33.1, 22.4, 13.9 (all Bu).
HRMS (FAB): m/z [M + H]+ calcd for C28H33N4O2: 457.2604;
found: 457.2620.
Acknowledgment
(15) Chardon-Noblat, S.; Sauvage, J.-P. Tetrahedron 1991, 47,
5123.
(16) Santangelo, F.; Casagrande, C.; Miragoli, G.; Vecchietti, V.
This work was supported by the Engineering and Physical Sciences
Research Council UK (Grant No. GR/N09503). We wish to ac-
knowledge a UCL Provost studentship to S.O.
Eur. J. Med. Chem. 1994, 29, 877.
(17) Croisy, M.; Huel, C.; Bisagni, E. Heterocycles 1997, 45,
683.
(18) Yamada, M.; Tanaka, Y.; Yoshimoto, Y.; Kuroda, S.;
Shimao, I. Bull. Chem. Soc. Jpn. 1992, 65, 1006.
(19) Bodige, S.; MacDonnell, F. M. Tetrahedron Lett. 1997, 38,
8159.
(20) Faust, R.; Weber, C.; Fiandanese, V.; Marchese, G.; Punzi,
A. Tetrahedron 1997, 53, 14655.
(21) Behr, O. M.; Eglinton, G.; Galbraith, A. R.; Raphael, R. A.
J. Chem. Soc. 1960, 3614.
References
(1) New Address: Dr. S. Ott, Institute of Chemistry, Department
of Organic Chemistry, BMC, Uppsala University, Box 599,
75124 Uppsala, Sweden, Fax: +46(18)4713818, E-Mail:
Sascha.Ott@fki.uu.se.
(2) New Address: Prof. Dr. R. Faust, Institute of Chemistry,
Faculty of Physical Sciences, University of Kassel,
Synthesis 2005, No. 18, 3135–3139 © Thieme Stuttgart · New York