Fluorine-containing 1,10-phenanthrolines synthesis: an original and efficient approach by the pyridine-ring formation reaction of N-propargyl-5,7-bis(trifluoroacetyl)-8-quinolylamine with various nucleophiles

Article abstract of DOI:10.1016/j.tet.2009.05.047

Novel fluorine-containing 1,10-phenanthrolines having a variety of substituents at the 3-position were easily synthesized in moderate yields by the pyridine-ring formation reaction of N-propargyl-5,7-bis(trifluoroacetyl)-8-quinolylamine with various amine

Full text of DOI:10.1016/j.tet.2009.05.047

Tetrahedron 65 (2009) 6189–6195
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Fluorine-containing 1,10-phenanthrolines synthesis: an original and efficient
approach by the pyridine-ring formation reaction of N-propargyl-5,7-bis-
(trifluoroacetyl)-8-quinolylamine with various nucleophiles
,
a
c
c
Dai Shibata a, Etsuji Okada b , Takayuki Miyaoku , Jerome Molette , Maurice Medebielle
*
´ ˆ
´
a Graduate School of Science and Technology, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
b Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan
c
´
´
´
´
`
´
Universite de Lyon, Universite Claude Bernard Lyon 1 (UCBL), Institut de Chimie et Biochimie Moleculaires et Supramoleculaires (ICBMS), Laboratoire de Synthese de Biomolecules
(LSB), UMR 5246 CNRS-UCBL-INSA Lyon-CPE Lyon, 43 Bd du 11 Novembre 1918, Villeurbanne 69622, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel fluorine-containing 1,10-phenanthrolines having a variety of substituents at the 3-position were
easily synthesized in moderate yields by the pyridine-ring formation reaction of N-propargyl-5,7-bis-
(trifluoroacetyl)-8-quinolylamine with various amines, thiols, and phenols. Unexpectedly, the reactive
intermediates 1,4-dihydro-1,10-phenanthrolin-4-ols were isolated for the first time in the reactions with
dialkylamines.
Received 27 February 2009
Received in revised form 18 May 2009
Accepted 18 May 2009
Available online 23 May 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
1,10-Phenanthrolines
Fluorine
Pyridine-ring formation
Propargylamines
8-Quinolylamines
1. Introduction
fluoroacetyl)-8-quinolylamine 29 react easily with various amines,
thiols and alcohols under mild conditions to afford the corre-
In recent years considerable attention has been paid to the de-
velopment of new methodologies for the synthesis of many kinds
of fluorine-containing heterocycles, since these compounds are
now widely recognized as important organic materials showing
interesting biological activities for their potential use in medicinal
and agricultural scientific fields.1
sponding N–N, N–S and N–O exchanged products 3 and 4 in ex-
cellent yields (Scheme 1). Moreover we succeeded in applying this
type of aromatic nucleophilic substitution to the simple syntheses
of various CF3-containing heterocycles having naphthalene10 and
quinoline11 skeletons.
1,10-Phenanthroline and the related derivatives2 have attracted
much attention for their biological properties such asantibacterial,3a,c
antifungal,3a and antitumor3b,d activities. They are also valuable
classes of heterocyclic compounds because of being applicable as
chelating ligands forming stable complexes with transition metals.4
Inparticular, some of these complexes have been used as useful novel
catalysts in phase-transfer5 and asymmetric6 reactions, and they are
also potential DNA binding agents,7 which can be expected to be
developed as novel probes of nucleic acid structure and function.
We have previously reported that N,N-dimethyl-2,4-bis(tri-
fluoroacetyl)-1-naphthylamine 18 and N,N-dimethyl-5,7-bis(tri-
NMe2
COCF3
Nu
X
X
COCF3
NuH
(NuH=RR'NH, RSH, ROH)
COCF3
COCF3
1: X=CH
2: X=N
3: X=CH
4: X=N
Scheme 1.
In continuation of these studies, it was found that N-propargyl-2,4-
bis(trifluoroacetyl)-1-naphthylamines 5, prepared by N–N ex-
change reaction of 1 with propargylamine, undergoes novel
pyridine-ring formation reaction with various nucleophiles to
give the corresponding fluorine-containing benzo[h]quinolines 6
in excellent yields (Scheme 2).12
* Corresponding author. Tel./fax: þ81 78 803 6194.
E-mail address: okaetsu@kobe-u.ac.jp (E. Okada).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.05.047

6190
D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
CHCl3). However, forced reaction conditions (in refluxing TFA) were
required for dimethyl- and diethylamino derivatives 8a and 8b. The
reason is not clear at this stage. Interestingly, the 6-trifluoroacetyl
group of prepared 1,10-phenanthrolines 9 was found to exist as
hydrate form and this phenomenon was not observed in the case of
benzo[h]quinolines 6. It is speculated that the increase, which is
HN
N
Nu
CF3
COCF3
NuH
(NuH=RR'NH, RSH, ROH)
COCF3
5
COCF3
6
caused by two pyridine rings (p-deficient system) fused to a central
Scheme 2.
benzene ring, of the electron-withdrawing ability of 1,10-phenan-
throline system makes the hydration of the trifluoroacetyl group
easier than that of benzo[h]quinoline system.
In connection to these syntheses, we have very recently repor-
ted that N-propargyl-5,7-bis(trifluoroacetyl)-8-quinolylamine
7
In contrast, when the reaction with bulky primary amine such as
tert-butylamine was performed under mild conditions (at room
temperature for 4 h), a mixture of dihydrophenanthrolinol 8d and
phenanthroline 9d was obtained but separation of the mixture was
unsuccessful. Therefore, we performed the two-step reaction in
a one-pot manner to obtain selectively the final target product 9d.
After stirring the solution of a mixture of 7 and tert-butylamine in
CH3CN for 4 h at room temperature, TFA (5 equiv) was added to the
reaction mixture and then it was further stirred for 5 min at the
same temperature to afford 9d in 58% yield (entry 4). In a similar
one-pot manner, aromatic primary amines, for example, p-anisi-
dine and p-chloroaniline, reacted in the presence of triethylamine
as a base to give the desired 1,10-phenanthrolines 9e and 9f in
moderate yields (entries 5 and 6). In this pyridine-ring formation
reaction, only 0.5 equiv of triethylamine was needed to force the
reaction to completion. Unfortunately, the reactions with less bulky
aliphatic primary amines such as methyl-, ethyl-, and i-propyl-
amines furnished a complex mixture of the corresponding N–N
exchanged 8-quinolylamine derivatives 4 (Nu: MeNH, EtNH, and
i-PrNH) and decomposed products.
Next, we attempted to carry out the pyridine-ring formation
reaction with various thiols (Scheme 4, Table 2). Reaction of 7 with
aliphatic thiols such as benzyl mercaptan, ethanethiol, propane-
thiol, and tert-butanethiol in the presence of t-BuOK (0.1 equiv,
entry 1; 0.5 equiv, entries 3–4 and 7–8; 1.0 equiv, entries 2 and 5–6)
took place in CH3CN at room temperature within 1 h to afford the
desired 3-alkylthiomethyl-1,10-phenanthrolines 10a–d in mode-
rate yields (entries 1–4). In the case of low boiling ethanethiol, the
reaction was performed with large amounts of reagent (5 equiv) to
provide 10b. Aromatic thiols such as p-substituted benzenethiols
also underwent quickly the pyridine-ring formation reaction under
undergoes the pyridine-ring formation reaction with amines to
afford the novel fluorine-containing 1,10-phenanthrolines 9 and
the isolation of the reactive intermediates 1,4-dihydro-1,10-phe-
nanthrolin-4-ols 8a–c.13 To the best of our knowledge, this was the
first example of the isolation of 1,4-dihydro-1,10-phenanthrolin-4-
ols as the precursor of 1,10-phenanthrolines.
Herein we report a full account of our systematic studies on this
type of pyridine-ring formation reaction including an extension of
the remarkable reactivityof 7 with various thiols and phenols, which
are considerably less reactive than amines. This reaction afforded an
easy and efficient way to introduce substitution diversity.
2. Results and discussion
The requisite starting material 7 was quantitatively prepared by
the aromatic nucleophilic N–N exchange reaction of 2 with
propargylamine.9
We first examined the reaction of 7 with secondary amines
(Scheme 3) and the results are summarized inTable 1. The cyclization
of 7 with dimethylamine proceeded rapidly at room temperature in
CH3CN to give the unexpected intermediate, 1,4-dihydro-1,10-phen-
anthrolin-4-ols 8a, in an almost quantitative yield without de-
hydration (entry 1; in the first step). Secondary amines such as
diethylamine and piperidine also reacted cleanly to provide dihy-
drophenanthrolinols 8b and 8c quantitatively (entries 2 and 3).
Treatment of dihydrophenanthrolinols 8a–c with trifluoroacetic
acid (TFA) caused dehydration to furnish the corresponding phen-
anthrolines 9a–c in 60–63% yields (entries 1–3; in the second
step). The dehydration of piperidino derivative 8c was carried out
under mild conditions (with 1 equiv of TFA at room temperature in
HN
HN
NR1R2
CF3
OH
N
NR1R2
CF3
R1R2NH (1 equiv.)
rt in CH3CN
1st step
N
COCF3
N
N
TFA
2nd step
COCF3
7
COCF3
8a-f
C(OH)2CF3
9a-f
(isolated for 8a-c)
Scheme 3.
Table 1
Synthesis of 1,10-phenanthrolines 9 by the reaction of 7 with amines
Entry
First step
R1R2NH
Second step
TFA (equiv)
Time (h)
Product
Yield (%)
Temp.
Time (min)
Solvent
Product
Yield (%)
1
2
3
Me2NHa
Et2NH
Piperidine
t-BuNH2
4-MeOC6H4NH2
4-ClC6H4NH2
2
2
1
4
4
4
8a
8b
8c
d
d
d
98
100
100
d
54
54
1
5
5
Reflux
Reflux
rt
rt
rt
rt
30
30
30
5
5
5
None
None
CHCl3
CH3CN
CH3CN
CH3CN
9a
9b
9c
9d
9e
9f
62b
60b
63b
58c
51c
58c
4
5d
6d
d
d
5
a
Aqueous solution (50%) of dimethylamine was used.
Isolated yields based on 8.
Isolated yields based on 7.
b
c
d
Triethylamine (0.5 equiv) was added.

D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
6191
similar conditions for aliphatic thiols, to give the corresponding
arylthiomethylated 1,10-phenanthrolines 10e–i (entries 5–9).
In the reaction with thiols and phenols, the formation of the
corresponding 1,4-dihydro-1,10-phenanthrolin-4-ols were also
established from the 1H NMR analysis of the crude mixtures. The
isolation of intermediates is unsuccessful but the final target, 1,10-
phenanthrolines were obtained after silica gel chromatography
without dehydration using TFA.
HN
N
YR3
CF3
R3YH (1 equiv.)
Base (a equiv.)
N
COCF3
N
rt in CH3CN
Two possible mechanistic pathways (path A and B) for the for-
mation of 1,10-phenanthrolines are presented in Scheme 5. In the
path A, the addition of nucleophiles, e.g., amines, to the terminal
acetylenic carbon and the attack of carbonyl carbon onto the in-
ternal acetylenic carbon occur concertedly to give the cyclization
product 80 having exo-methylene moiety. The subsequent 1,3-shift
of allylic hydrogen in 80 takes place to afford the intermediates, 1,4-
dihydro-1,10-phenanthrolin-4-ols 8, which undergoes dehydration
to give 1,10-phenanthrolines 9. In the path B, the tautomerization of
keto to enol form causes the isomerization of propargyl to allenyl
group and subsequent intramolecular cyclization gives the 3-
methylene-1,10-phenanthroline derivative. Then, this product re-
acts with amines to give 8 leading to 9. More studies are underway
to elucidate clearly the mechanism.
The structures of all new compounds (8–11) were easily deter-
mined on the basis of their 1H NMR and IR spectra, together with
elemental analyses. For example, in 1H NMR spectrum of 8a, two
adjacent protons (amine and olefin protons) at 1- and 2-positions
appeared at 8.88 and 6.72 ppm as doublets with coupling constant
J¼4.0 Hz. When the H–D exchange of the amine proton (H-1) was
carried out, the multiplicity of olefin proton (H-2) signal changed to
singlet. The data clearly shows that the structure of the isolated
intermediate is not 80 but 8.
COCF3
7
C(OH)2CF3
10a-i: Y = S
11a-d: Y = O
Scheme 4.
Table 2
Synthesis of 1,10-phenanthrolines 10 and 11 by the reaction of 7 with thiols and
phenols
Entry
R3YH
Base
a (equiv) Time (h)
Product Yielda (%)
1
2
3
4
5
6
7
8
PhCH2SH
EtSHb
PrSH
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
i-Pr2NEt
Et3N
0.1
1
0.5
0.5
1
1
1
1
1
1
2
1
1
1
8
2
8
8
10a
10b
10c
10d
10e
10f
10g
10h
10i
11a
11b
11c
11d
55
54
46
44
48
45
58
58
44
58
53
46
54
t-BuSH
4-MeOC6H4SH
4-MeC6H4SH
PhSH
4-ClC6H4SH
4-NO2C6H4SH
4-MeOC6H4OH
4-MeC6H4OH
PhOH
1
0.5
0.5
1
0.5
0.5
0.5
0.5
9
10
11
12
13
i-Pr2NEt
i-Pr2NEt
4-ClC6H4OH
a
Isolated yields.
EtSH (5 equiv) was used.
b
It is noteworthy that we first succeeded in the isolation of the
intermediates 8a–c, which are the precursors of stable aromatized
final products, 1,10-phenanthrolines 9a–c, and which seem to be
unstable. This is a great difference in reactivity between the 8-
quinoline system 7 and the naphthalene one 5, as in the naph-
thalene system this type of intermediate, for example, 12, was not
isolated and also not detected (Fig. 1).12 Probably, it is reasonable to
postulate that in 8a–c the additional hydrogen bond between H-1
and N-10, which cannot exist in the naphthalene system 12, has
contributed to the stability of 8a–c, namely, has interrupted the
dehydration accompanied by aromatization. We attempted the
NMR experiment, where 8a was dissolved in DMSO-d6 as a solvent
to disfavor the hydrogen bond between H-1 and N-10, allowed to
stand at 33 ꢀC and the reaction progress was monitored by 1H NMR.
Furthermore, the present pyridine-ring formation reactions
were applied to phenols (Scheme 4, Table 2) and alcohols. The
cyclization formation of 7 with p-substituted phenols pro-
ceeded easily in the presence of N,N-diisopropylethylamine or
triethylamine (0.5 equiv) as a base in CH3CN to produce the
corresponding 1,10-phenanthrolines 11a–d having aryloxy-
methyl group at the 3-position, in moderate yields (entries
10–13). All the cyclization reactions with thiols and phenols
did not proceed in the absence of base. However, in spite of
our efforts, only decomposed products were formed in the
reaction with any alcohols even under the more severe
conditions.
Path A
H
H
NR1R2
OH
CF3
N
NR1R2
CF3
N
NR1R2
H
N
N
N
N
R1R2NH
- H2O
1,3-H Shift
O
7
CF3
COCF3
COCF3
8'
C(OH)2CF3
9
8
Path B
H
O
H
R1R2NH
H
H
N
C
H
H
C
H
NH
H
NH
O
NH O
N
H
OH
N
N
N
CF3
CF3
CF3
CF3
COCF3
COCF3
COCF3
COCF3
Scheme 5.

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D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
1
J¼8.6 Hz, H-7), 8.96 (br d, 1H, J¼3.9 Hz, H-9), 8.79 (d, 1H, J¼4.6 Hz,
H
H
NMe2
H
NMe2
H
N
N
no hydrogen bond
NH), 8.71 (s, 1H, H-5), 7.60 (dd, 1H, J¼3.9, 8.6 Hz, H-8), 6.73 (d, 1H,
J¼4.6 Hz, H-2), 4.06 (d, 1H, Jgem¼13.2 Hz, CH2), 3.00 (d, 1H,
Jgem¼13.2 Hz, CH2), 2.85–2.78 (m, 2H, NCH2CH3), 2.47–2.37 (br m,
2H, NCH2CH3), 1.07 (t, 6H, J¼6.6 Hz, CH3); 13C NMR (126 MHz,
10
N
O
O
CF3
CF3
COCF3
8a
COCF3
12
CDCl3):
d
179.8 (q, JCF¼33.5 Hz), 148.8, 139.6, 136.7, 136.6, 134.7,
127.4, 127.3, 126.1 (q, JCF¼290.9 Hz), 124.7, 117.0 (q, JCF¼292.6 Hz),
116.9, 112.8, 104.3, 72.8 (q, JCF¼30.2 Hz), 60.4, 45.5, 10.7; IR (KBr,
cmꢁ1): 3409, 3089, 1698, 1676; Anal. Calcd for C20H19F6N3O2: C,
53.69; H, 4.28; N, 9.39. Found: C, 53.77; H, 4.34; N, 9.26.
Figure 1.
It was found that 8a is gradually converted to 9a under the
above-described conditions as follows: conversion/standing time;
38%/3 days; 100%/7 days. This result supports our speculation on
stabilization of the intermediates 8a–c by the intramolecular hy-
drogen bond.
4.2.3. 3-Piperidinomethyl-6-trifluoroacetyl-4-trifluoromethyl-1,4-
dihydro[1,10]phenanthrolin-4-ol (8c)
Compound 8c: 100%; mp 172–173 ꢀC (dec) (MeCN/H2O); 1H
NMR (500 MHz, CDCl3):
d
9.75–9.41 (br,1H, OH), 9.53 (dd,1H, J¼1.5,
3. Conclusion
8.5 Hz, H-7), 8.84 (dd, 1H, J¼1.5, 4.0 Hz, H-9), 8.81 (br d, 1H,
J¼4.0 Hz, NH), 8.72 (br s, 1H, H-5), 7.65 (dd, 1H, J¼4.0, 8.5 Hz, H-8),
6.68 (d, 1H, J¼4.0 Hz, H-2), 3.93 (d, 1H, Jgem¼13.0 Hz, CH2), 3.05–
2.19 (br, 4H, NCH2CH2), 2.90 (d, 1H, Jgem¼13.0 Hz, CH2), 1.60–1.57
In summary, we succeeded in extending the pyridine-ring for-
mation reaction of N-propargyl-8-quinolylamine derivative 7 with
amines to those with thiols and phenols and in providing an effi-
cient synthetic method for CF3-containing 1,10-phenanthrolines 9,
which are not easily obtained by other methods. The methodology
presented is quite remarkable since no any kind of activation of the
propargylamine system was needed to promote addition of the
nucleophiles and subsequent ring formation. The mechanism of
this reaction is not yet fully established although two reasonable
mechanistic pathways have been presented.
(m, 6H, NCH2CH2CH2CH2); 13C NMR (126 MHz, CDCl3):
d 179.9 (q,
JCF¼34.0 Hz), 148.9, 139.4, 136.8, 136.8, 134.9, 127.3, 127.2, 126.1 (q,
JCF¼290.5 Hz), 124.9, 117.1, 117.0 (q, JCF¼293.0 Hz), 112.8, 104.0, 72.7
(q, JCF¼30.2 Hz), 61.0, 53.8, 25.8, 24.0; IR (KBr, cmꢁ1): 3394, 3085,
1692, 1676; Anal. Calcd for C21H19F6N3O2: C, 54.90; H, 4.17; N, 9.15.
Found: C, 55.00; H, 3.80; N, 9.43.
4.3. A typical procedure for the synthesis of 1,10-
phenanthrolines (9a–c) from 1,4-dihydro-1,10-
phenanthrolin-4-ols (8a–c)
4. Experimental
4.1. General
A solution of 8a (210 mg, 0.5 mmol) in CF3CO2H (2 mL) was
stirred at reflux temperature for 30 min. The mixture was washed
with saturated aqueous solution of Na2CO3, extracted with AcOEt,
and dried over Na2SO4. The solvent was evaporated in vacuo and
the crude product was purified by recrystallization from n-hexane
and AcOEt to give 9a (130 mg, 62%).
Mps were determined on an electrothermal digital melting
point apparatus and are uncorrected. NMR spectra were obtained
with a Bruker AVANCE 500 spectrometer (1H at 500 MHz, 13C at
126 MHz) using TMS as an internal standard and IR spectra were
taken with a PerkinElmer ONE FT-IR spectrometer. Microanalyses
were taken with a YANACO CHN-Coder MT-5 analyzer.
4.3.1. 1-(8-Dimethylaminomethyl-7-trifluoromethyl[1,10]-
phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (9a)
Compound 9a: 62%; mp 161–162 ꢀC (n-hexane/AcOEt); 1H NMR
4.2. A typical procedure for the synthesis of 1,4-dihydro-1,10-
phenanthrolin-4-ols (8a–c)
(500 MHz, CD3CN/DMSO-d6):
d
9.38 (d,1H, J¼8.5 Hz, H-4), 9.30 (s,1H,
H-9), 9.12 (d, 1H, J¼4.0 Hz, H-2), 8.79 (s, 1H, H-6), 7.95 (br s, 2H, OH),
7.74 (dd,1H, J¼4.0, 8.5 Hz, H-3), 3.88(s, 2H, CH2), 2.28(s, 6H, N(CH3)2);
To a solution of 79 (187 mg, 0.5 mmol) in CH3CN (5 mL) was
added aqueous solution (50%) of dimethylamine (51 mg,
0.56 mmol) and the mixture was stirred at room temperature for
2 h. Evaporation of the solvent in vacuo gave practically pure 8a
(205 mg, 98%).
13C NMR (126 MHz, CDCl3/DMSO-d6):
d 153.9, 149.9, 146.3, 145.4,
136.4, 134.9, 132.1 (q, JCF¼30.7 Hz), 126.7, 124.5 (q, JCF¼283.0 Hz),
124.1, 124.1, 123.6 (q, JCF¼289.3 Hz),123.0,122.3, 94.3 (q, JCF¼31.4 Hz),
58.9, 45.2; IR (KBr, cmꢁ1): 3352, 3115; Anal. Calcd for C18H15F6N3O2: C,
51.56; H, 3.61; N, 10.02. Found: C, 51.83; H, 3.85; N, 9.75.
4.2.1. 3-Dimethylaminomethyl-6-trifluoroacetyl-4-trifluoromethyl-
1,4-dihydro[1,10]phenanthrolin-4-ol (8a)
4.3.2. 1-(8-Diethylaminomethyl-7-trifluoromethyl[1,10]-
phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (9b)
Compound 9b: 60%; mp 130–131 ꢀC (AcOEt); 1H NMR (500 MHz,
Compound 8a: 98%; mp 123–124 ꢀC (dec) (n-hexane/AcOEt); 1H
NMR (500 MHz, CDCl3):
d
9.48 (dd, 1H, J¼1.5, 8.5 Hz, H-7), 8.88 (br
d, 1H, J¼4.0 Hz, NH), 8.81 (dd, 1H, J¼1.5, 4.0 Hz, H-9), 8.72 (s, 1H, H-
5), 7.76–7.28 (br, 1H, OH), 7.62 (dd, 1H, J¼4.0, 8.5 Hz, H-8), 6.72 (d,
1H, J¼4.0 Hz, H-2), 3.99 (d, 1H, Jgem¼13.0 Hz, CH2), 2.82 (d, 1H,
Jgem¼13.0 Hz, CH2), 2.31 (s, 6H, N(CH3)2); 13C NMR (126 MHz,
CDCl3/DMSO-d6):
d
9.60 (s, 1H, H-9), 9.45 (d, 1H, J¼8.4 Hz, H-4), 9.16
(d, 1H, J¼3.9 Hz, H-2), 8.87 (s, 1H, H-6), 7.87 (br s, 2H, OH), 7.68 (dd,
1H, J¼3.9, 8.4 Hz, H-3), 4.05 (s, 2H, CH2), 2.60 (q, 4H, J¼7.0 Hz,
NCH2CH3), 1.07 (t, 6H, J¼7.0 Hz, CH3); 13C NMR (126 MHz, CDCl3/
CDCl3):
d
179.9 (q, JCF¼33.4 Hz), 148.9, 139.4, 136.8, 136.6, 134.9,
DMSO-d6): d 153.9, 149.9, 146.3, 145.8, 136.7, 134.6, 132.1 (q,
127.4, 127.3, 126.0 (q, JCF¼294.3 Hz), 124.9, 117.2, 117.0 (q,
JCF¼293.0 Hz), 112.8, 104.4, 72.8 (q, JCF¼30.2 Hz), 61.5, 44.2; IR (KBr,
cmꢁ1): 3402, 3094, 1697, 1676; Anal. Calcd for C18H15F6N3O2: C,
51.56; H, 3.61; N, 10.02. Found: C, 51.63; H, 3.32; N, 9.89.
JCF¼30.2 Hz), 126.8, 124.8, 124.7 (q, JCF¼279.2 Hz), 124.5, 123.6 (q,
JCF¼293.0 Hz), 122.7, 122.4, 94.7 (q, JCF¼32.7 Hz), 53.7 (q, JCF¼3.8 Hz),
47.2,12.0; IR (KBr, cmꢁ1): 3386, 3182; Anal. Calcd for C20H19F6N3O2: C,
53.69; H, 4.28; N, 9.39. Found: C, 53.67; H, 4.37; N, 9.32.
4.2.2. 3-Diethylaminomethyl-6-trifluoroacetyl-4-trifluoromethyl-
1,4-dihydro[1,10]phenanthrolin-4-ol (8b)
4.3.3. 2,2,2-Trifluoro-1-(8-piperidinomethyl-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (9c)
Compound 8b: 100%; mp 131–132 ꢀC (dec) (n-hexane/AcOEt);
Compound 9c: 63%; mp 140–141 ꢀC (EtOH); 1H NMR (500 MHz,
1H NMR (500 MHz, CDCl3):
d
9.75–9.28 (br, 1H, OH), 9.47 (d, 1H,
CDCl3/DMSO-d6):
d
9.47 (s, 1H, H-9), 9.44 (d, 1H, J¼8.4 Hz, H-4), 9.16

D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
6193
(d, 1H, J¼3.8 Hz, H-2), 8.85 (s, 1H, H-6), 8.00 (br s, 2H, OH), 7.70 (dd,
4.5. A typical procedure for the synthesis of 1,10-
phenanthrolines (10a–i) by the pyridine-ring formation
reaction of 7 with thiols
1H, J¼3.8, 8.4 Hz, H-3), 3.94 (s, 2H, CH2), 2.48 (br s, 4H, NCH2CH2),
1.59 (br s, 4H, NCH2CH2CH2), 1.47 (br s, 2H, NCH2CH2CH2); 13C NMR
(126 MHz, CDCl3/DMSO-d6):
d 153.8, 149.8, 146.4, 145.7, 136.6,
134.8, 132.4 (q, JCF¼31.4 Hz), 126.8, 124.6 (q, JCF¼281.7 Hz), 124.4,
124.4, 123.6 (q, JCF¼288.0 Hz), 122.7, 122.5, 94.6 (q, JCF¼32.7 Hz),
58.4, 54.4, 25.8, 24.0; IR (KBr, cmꢁ1): 3341, 3121; Anal. Calcd for
C21H19F6N3O2: C, 54.90; H, 4.17; N, 9.15. Found: C, 55.19; H, 4.18; N,
8.85.
To a solution of benzyl mercaptan (0.06 mL, 0.5 mmol) and t-
BuOK (6 mg, 0.05 mmol) in CH3CN (5 mL) was added 7 (187 mg,
0.5 mmol) and the mixture was stirred at room temperature for 1 h.
The mixture was washed with 1.0 N hydrochloric acid, extracted
with AcOEt, and dried over Na2SO4. Evaporation of the solvent gave
a crude mixture, which was submitted to column chromatography
on silica gel eluting with n-hexane/AcOEt (1:2) to give 10a (137 mg,
55%).
4.4. A typical procedure for the one-pot synthesis of 1,10-
phenanthroline (9d–f) from N-propargyl-5,7-bis-
(trifluoroacetyl)-8-quinolylamine (7)
4.5.1. 1-(8-Benzylthiomethyl-7-trifluoromethyl[1,10]-
phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (10a)
Compound 10a: 55%; mp 137–138 ꢀC (AcOEt); 1H NMR
To a solution of 7 (187 mg, 0.5 mmol) in CH3CN (5 mL) were
added p-anisidine (65 mg, 0.53 mmol) and triethylamine (25 mg,
0.25 mmol) and the mixture was stirred at room temperature for
4 h. Without work-up to the reaction mixture was added CF3CO2H
(0.19 mL, 2.6 mmol) and then it was further stirred for 5 min at
room temperature. The mixture was washed with saturated aque-
ous solution of Na2CO3, extracted with AcOEt, and dried over
Na2SO4. Evaporation of the solvent gave a crude mixture, which
was submitted to column chromatography on silica gel eluting with
n-hexane/AcOEt (1:1) to give 9e (127 mg, 51%).
(500 MHz, CDCl3/DMSO-d6):
d
9.45 (d, 1H, J¼8.3 Hz, H-4), 9.18 (br s,
1H, H-2), 9.04 (s, 1H, H-9), 8.85 (s, 1H, H-6), 7.68 (dd, 1H, J¼4.0,
8.3 Hz, H-3), 7.62 (br s, 2H, OH), 7.39–7.27 (m, 4H, Harom), 7.23 (t,1H,
J¼7.1 Hz, Harom), 4.05 (s, 2H, CH2S), 3.76 (s, 2H, CH2Ph); 13C NMR
(126 MHz, CDCl3/DMSO-d6): d 153.8, 150.0, 146.4, 145.6, 137.1, 136.9,
135.2, 132.1, 131.9 (q, JCF¼30.2 Hz), 128.9, 128.5, 127.2, 127.0, 124.4
(q, JCF¼279.2 Hz), 124.4, 123.6 (q, JCF¼289.3 Hz), 123.0, 123.0, 94.7
(q, JCF¼32.7 Hz), 36.4, 31.7; IR (KBr, cmꢁ1): 3368, 3121; Anal. Calcd
for C23H16F6N2O2S: C, 55.42; H, 3.24; N, 5.62. Found: C, 55.64; H,
3.30; N, 5.34.
4.4.1. 1-(8-(tert-Butylaminomethyl)-7-trifluoromethyl[1,10]-
phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (9d)
Compound 9d: 58%; mp 167–168 ꢀC (n-hexane/AcOEt); 1H NMR
4.5.2. 1-(8-Ethylthiomethyl-7-trifluoromethyl[1,10]phenanthrolin-
5-yl)-2,2,2-trifluoroethane-1,1-diol (10b)
(500 MHz, CDCl3/DMSO-d6):
d
9.41 (d, 1H, J¼8.5 Hz, H-4), 9.39 (s,
1H, H-9), 9.16 (d, 1H, J¼4.0 Hz, H-2), 8.85 (s, 1H, H-6), 7.65 (dd, 1H,
J¼4.0, 8.5 Hz, H-3), 7.51–7.25 (br, 1H, NH), 7.35 (s, 2H, OH), 4.17 (s,
2H, CH2), 1.22 (s, 9H, C(CH3)3); 13C NMR (126 MHz, CDCl3/DMSO-
Compound 10b: 54%; mp 146–147 ꢀC (AcOEt); 1H NMR
(500 MHz, CDCl3/DMSO-d6):
d
9.44 (d, 1H, J¼8.2 Hz, H-4), 9.19 (s,
1H, H-9), 9.16 (br s, 1H, H-2), 8.82 (s, 1H, H-6), 8.09 (br s, 2H, OH),
7.73 (dd, 1H, J¼3.8, 8.2 Hz, H-3), 4.22 (s, 2H, CH2S), 2.58 (q, 2H,
J¼7.3 Hz, CH2CH3), 1.27 (t, 3H, J¼7.3 Hz, CH3); 13C NMR (126 MHz,
d6):
d
154.9, 149.9, 146.3, 145.2, 136.4, 135.1, 131.5 (q, JCF¼29.3 Hz),
126.8, 124.7, 124.3 (q, JCF¼285.6 Hz), 124.0, 123.5 (q, JCF¼290.5 Hz),
123.1, 121.9, 94.3 (q, JCF¼31.2 Hz), 59.7, 41.7, 27.4; IR (KBr, cmꢁ1):
3473, 3352, 3148; Anal. Calcd for C20H19F6N3O2: C, 53.69; H, 4.28; N,
9.39. Found: C, 53.94; H, 4.19; N, 9.23.
DMSO-d6):
d 154.3, 150.1, 145.3, 144.7, 136.3, 134.8, 133.5, 130.4 (q,
JCF¼30.2 Hz), 126.3, 124.3 (q, JCF¼277.7 Hz), 123.7, 123.5 (q,
JCF¼286.9 Hz), 123.4, 122.1, 94.0 (q, JCF¼33.0 Hz), 31.2, 25.4, 14.4; IR
(KBr, cmꢁ1): 3368, 3126; Anal. Calcd for C18H14F6N2O2S: C, 49.54; H,
3.23; N, 6.42. Found: C, 49.77; H, 3.29; N, 6.13.
4.4.2. 2,2,2-Trifluoro-1-(8-(4-methoxyphenylaminomethyl)-7-
trifluoromethyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (9e)
Compound 9e: 51%; mp 136–137 ꢀC (dec) (n-hexane/AcOEt); 1H
4.5.3. 2,2,2-Trifluoro-1-(8-propylthiomethyl-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (10c)
Compound 10c: 46%; mp 151–152 ꢀC (AcOEt); 1H NMR
NMR (500 MHz, CDCl3/DMSO-d6):
d
9.44 (d, 1H, J¼9.0 Hz, H-4), 9.41
(s, 1H, H-9), 9.15 (d, 1H, J¼4.0 Hz, H-2), 8.88 (s, 1H, H-6), 7.68 (br s,
2H, OH), 7.66 (dd, 1H, J¼4.0, 9.0 Hz, H-3), 6.72 (d, 2H, J¼8.5 Hz,
Harom), 6.60 (d, 2H, J¼8.5 Hz, Harom), 4.90–4.68 (br, 1H, NH), 4.81 (s,
2H, CH2), 3.70 (s, 3H, OCH3); 13C NMR (126 MHz, CDCl3/DMSO-d6):
(500 MHz, DMSO-d6):
d
9.36 (d, 1H, J¼8.3 Hz, H-4), 9.28 (s, 1H, H-9),
9.17 (br s,1H, H-2), 8.75 (s, 1H, H-6), 8.47 (br s, 2H, OH), 7.87 (dd,1H,
J¼3.6, 8.3 Hz, H-3), 4.25 (s, 2H, CH2S), 2.58–2.52 (m, 2H, SCH2CH2),
1.55 (sext, 2H, J¼7.1 Hz, SCH2CH2), 0.91 (t, 3H, J¼7.1 Hz, CH3); 13C
d
152.6, 152.1, 150.0, 149.9, 146.4, 145.6, 136.7, 135.0, 131.8 (q,
JCF¼31.4 Hz), 126.8, 124.8 (q, JCF¼280.5 Hz), 124.2, 123.6 (q,
JCF¼289.3 Hz), 123.0, 122.8, 122.4, 114.9, 114.0, 94.6 (q, JCF¼32.7 Hz),
55.6, 55.4; IR (KBr, cmꢁ1): 3415, 3363, 3115; Anal. Calcd for
C23H17F6N3O3: C, 55.54; H, 3.44; N, 8.45. Found: C, 55.75; H, 3.47; N,
8.23.
NMR (126 MHz, DMSO-d6): d 154.3, 150.1, 145.8, 145.1, 135.9, 134.9,
133.3, 130.2 (q, JCF¼28.5 Hz), 126.3, 124.4 (q, JCF¼277.5 Hz), 123.7,
123.6 (q, JCF¼289.3 Hz), 123.2, 122.0, 94.1 (q, JCF¼32.7 Hz), 33.4,
31.5, 22.3, 13.0; IR (KBr, cmꢁ1): 3366, 3115; Anal. Calcd for
C19H16F6N2O2S: C, 50.67; H, 3.58; N, 6.22. Found: C, 50.69; H, 3.47;
N, 6.03.
4.4.3. 1-(8-(4-Chlorophenylaminomethyl)-7-trifluoromethyl-
[1,10]phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (9f)
Compound 9f: 58%; mp 135–136 ꢀC (AcOEt); 1H NMR (500 MHz,
4.5.4. 1-(8-(tert-Butylthiomethyl)-7-trifluoromethyl[1,10]-
phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (10d)
Compound 10d: 44%; mp 168–169 ꢀC (AcOEt); 1H NMR
CDCl3/DMSO-d6):
d
9.46 (d,1H, J¼8.5 Hz, H-4), 9.40 (s, 1H, H-9), 9.13
(d, 1H, J¼4.0 Hz, H-2), 8.85 (s, 1H, H-6), 8.03 (br s, 2H, OH), 7.70 (dd,
1H, J¼4.0, 8.5 Hz, H-3), 6.69 (d, 2H, J¼8.6 Hz, Harom), 6.58 (d, 2H,
J¼8.6 Hz, Harom), 4.79 (s, 2H, CH2), 3.45–3.10 (br, 1H, NH); 13C NMR
(500 MHz, CDCl3/DMSO-d6):
d
9.47 (d, 1H, J¼8.5 Hz, H-4), 9.23 (s,
1H, H-9), 9.17 (d, 1H, J¼4.0 Hz, H-2), 8.84 (s, 1H, H-6), 8.01 (br s, 2H,
OH), 7.72 (dd, 1H, J¼4.0, 8.5 Hz, H-3), 4.22 (s, 2H, CH2), 1.44 (s, 9H,
(126 MHz, CDCl3/DMSO-d6):
d
152.6, 151.9, 149.7, 146.2, 145.4, 141.7,
C(CH3)3); 13C NMR (126 MHz, CDCl3/DMSO-d6):
d 154.5, 149.6,
136.8, 135.0, 133.4, 131.7 (q, JCF¼30.6 Hz), 126.8, 124.8 (q,
JCF¼279.6 Hz), 124.2, 123.5 (q, JCF¼289.8 Hz), 122.8, 122.4, 114.8,
113.8, 94.5 (q, JCF¼31.4 Hz), 55.5; IR (KBr, cmꢁ1): 3485, 3291, 3117;
Anal. Calcd for C22H14ClF6N3O2: C, 52.66; H, 2.81; N, 8.37. Found: C,
52.82; H, 3.02; N, 8.00.
145.5, 144.9, 137.1, 135.2, 132.3, 131.5 (q, JCF¼30.7 Hz), 126.8, 124.2
(q, JCF¼279.2 Hz), 124.2, 123.5 (q, JCF¼291.8 Hz), 123.0, 122.5, 94.3
(q, JCF¼32.7 Hz), 43.9, 30.6, 29.0; IR (KBr, cmꢁ1): 3383, 3126; Anal.
Calcd for C20H18F6N2O2S: C, 51.72; H, 3.91; N, 6.03. Found: C, 51.78;
H, 3.96; N, 5.92.

6194
D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
4.5.5. 2,2,2-Trifluoro-1-(8-(4-methoxyphenylthiomethyl)-7-
trifluoromethyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (10e)
Compound 10e: 48%; mp 185–186 ꢀC (AcOEt); 1H NMR
C22H13F6N3O4S: C, 49.91; H, 2.48; N, 7.94. Found: C, 50.27; H, 2.41;
N, 7.64.
(500 MHz, CDCl3/DMSO-d6):
d
9.42 (d, 1H, J¼8.5 Hz, H-4), 9.16 (d,
4.6. A typical procedure for the synthesis of 1,10-
phenanthrolines (11a–d) by the pyridine-ring formation
reaction of 7 with phenols
1H, J¼4.0 Hz, H-2), 8.84 (s, 1H, H-9 or 6), 8.75 (s, 1H, H-6 or 9), 7.66
(dd, 1H, J¼4.0, 8.5 Hz, H-3), 7.27 (br s, 2H, OH), 7.26 (d, 2H, J¼8.5 Hz,
Harom), 6.77 (d, 2H, J¼8.5 Hz, Harom), 4.38 (br s, 2H, CH2), 3.77 (s, 3H,
OCH3); 13C NMR (126 MHz, DMSO-d6):
d
160.0, 154.5, 150.6, 146.3,
To a solution of 7 (187 mg, 0.5 mmol) in CH3CN (5 mL) were
added p-methoxyphenol (62 mg, 0.5 mmol) and N,N-diisopropyl-
ethylamine (32 mg, 0.25 mmol) and the mixture was stirred at
room temperature for 8 h. Evaporation of the solvent gave a crude
mixture, which was submitted to column chromatography on silica
gel eluting with n-hexane/AcOEt (1:1) to give 11a (145 mg, 58%).
145.7, 136.3, 135.7, 135.4, 132.8, 130.7 (q, JCF¼30.2 Hz), 126.8, 124.9
(q, JCF¼278.0 Hz), 124.2, 124.1 (q, JCF¼290.5 Hz), 123.7, 123.4, 122.4,
115.3, 94.6 (q, JCF¼32.7 Hz), 55.7, 36.7; IR (KBr, cmꢁ1): 3385, 3121;
Anal. Calcd for C23H16F6N2O3S: C, 53.70; H, 3.13; N, 5.45. Found: C,
53.42; H, 3.33; N, 5.54.
4.5.6. 2,2,2-Trifluoro-1-(8-(p-tolylthiomethyl)-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (10f)
4.6.1. 2,2,2-Trifluoro-1-(8-(4-methoxyphenoxymethyl)-7-
trifluoromethyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (11a)
Compound 11a: 58%; mp 167–168 ꢀC (AcOEt); 1H NMR
Compound 10f: 45%; mp 159–160 ꢀC (AcOEt); 1H NMR
(500 MHz, DMSO-d6):
d
9.33 (d, 1H, J¼8.3 Hz, H-4), 9.13 (br s, 1H, H-
(500 MHz, CDCl3/DMSO-d6): d 9.49–9.48 (m, 2H, H-4, H-9), 9.18 (d,
2), 8.93 (s, 1H, H-9), 8.72 (s, 1H, H-6), 8.41 (br s, 2H, OH), 7.84 (dd,
1H, J¼3.8, 8.3 Hz, H-3), 7.28 (d, 2H, J¼7.5 Hz, Harom), 7.12 (d, 2H,
J¼7.5 Hz, Harom), 4.62 (s, 2H, CH2), 2.27 (s, 3H, CH3); 13C NMR
1H, J¼4.0 Hz, H-2), 8.88 (s,1H, H-6), 8.00 (br s, 2H, OH), 7.73 (dd,1H,
J¼4.0, 8.5 Hz, H-3), 6.97 (d, 2H, J¼8.8 Hz, Harom), 6.85 (d, 2H,
J¼8.8 Hz, Harom), 5.51 (br s, 2H, CH2), 3.76 (s, 3H, CH3); 13C NMR
(126 MHz, DMSO-d6):
d
154.4,150.6,146.4,145.6,138.0,136.4,135.4,
(126 MHz, CDCl3/DMSO-d6): d 155.4, 152.0, 151.8, 149.9, 147.0, 145.4,
132.7, 132.6, 130.8 (q, JCF¼30.2 Hz), 130.3, 130.0, 126.9, 124.8 (q,
JCF¼281.7 Hz), 124.2, 124.0 (q, JCF¼288.6 Hz), 123.7, 122.4, 94.6 (q,
JCF¼32.7 Hz), 35.7, 21.1; IR (KBr, cmꢁ1): 3374, 3110; Anal. Calcd for
C23H16F6N2O2S: C, 55.43; H, 3.24; N, 5.62. Found: C, 55.37; H, 3.61;
N, 5.29.
137.0, 135.4, 132.1 (q, JCF¼31.4 Hz), 129.9, 127.2, 124.4 (q,
JCF¼279.2 Hz), 124.2, 123.5 (q, JCF¼290.5 Hz), 123.1, 122.4, 116.1,
114.7, 94.6 (q, JCF¼32.7 Hz), 66.8, 55.5; IR (KBr, cmꢁ1): 3352, 3121;
Anal. Calcd for C23H16F6N2O4: C, 55.43; H, 3.24; N, 5.62. Found: C,
55.41; H, 3.26; N, 5.62.
4.5.7. 2,2,2-Trifluoro-1-(8-phenylthiomethyl-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (10g)
Compound 10g: 58%; mp 145–146 ꢀC (AcOEt); 1H NMR
4.6.2. 2,2,2-Trifluoro-1-(8-(p-tolyloxymethyl)-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (11b)
Compound 11b: 53%; mp 171–172 ꢀC (AcOEt); 1H NMR
(500 MHz, DMSO-d6):
d
9.34 (d, 1H, J¼8.6 Hz, H-4), 9.13 (d, 1H,
(500 MHz, CD3CN/DMSO-d6): d 9.46 (s, 1H, H-9), 9.38 (d, 1H,
J¼4.1 Hz, H-2), 9.02 (s, 1H, H-9), 8.72 (s,1H, H-6), 8.42 (br s, 2H, OH),
7.85 (dd, 1H, J¼4.1, 8.6 Hz, H-3), 7.41 (d, 2H, J¼7.0 Hz, Harom), 7.33–
7.27 (m, 3H, Harom), 4.69 (s, 2H, CH2); 13C NMR (126 MHz, DMSO-
J¼8.5 Hz, H-4), 9.14 (d, 1H, J¼4.0 Hz, H-2), 8.79 (q, 1H, JHF¼2.0 Hz,
H-6), 7.76 (dd, 1H, J¼4.0, 8.5 Hz, H-3), 7.71–7.59 (br, 2H, OH), 7.15 (d,
2H, J¼8.5 Hz, Harom), 6.98 (d, 2H, J¼8.5 Hz, Harom), 5.54 (q, 2H,
JHF¼1.5 Hz, CH2), 2.28 (s, 3H, CH3); 13C NMR (126 MHz, DMSO-d6):
d6): d 154.5, 150.6, 146.3, 145.5, 136.5, 135.4, 133.9,132.3, 131.9,130.9
(q, JCF¼28.9 Hz), 129.7, 129.1, 126.9, 124.8 (q, JCF¼276.8 Hz), 124.1,
124.0 (q, JCF¼291.7 Hz), 123.7, 122.4, 94.6 (q, JCF¼32.7 Hz), 35.1; IR
(KBr, cmꢁ1): 3335, 3121; Anal. Calcd for C22H14F6N2O2S: C, 54.55; H,
2.91; N, 5.78. Found: C, 54.62; H, 3.07; N, 5.56.
d
155.8, 152.6, 150.2, 146.8, 145.1, 135.9, 135.1, 131.5 (q, JCF¼31.2 Hz),
130.1, 129.9, 129.9, 126.6, 124.2 (q, JCF¼278.6 Hz), 123.6, 123.5 (q,
JCF¼287.8 Hz), 123.4, 121.7, 114.7, 94.1 (q, JCF¼32.7 Hz), 65.8, 20.0; IR
(KBr, cmꢁ1): 3352, 3122; Anal. Calcd for C23H16F6N2O3: C, 57.27; H,
3.34; N, 5.81. Found: C, 57.50; H, 3.40; N, 5.51.
4.5.8. 1-(8-(4-Chlorophenylthiomethyl)-7-trifluoromethyl-
[1,10]phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (10h)
Compound 10h: 58%; mp 144–145 ꢀC (AcOEt); 1H NMR
4.6.3. 2,2,2-Trifluoro-1-(8-phenoxymethyl-7-trifluoro-
methyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (11c)
Compound 11c: 46%; mp 158–159 ꢀC (AcOEt); 1H NMR
(500 MHz, DMSO-d6):
d
9.34 (d, 1H, J¼8.4 Hz, H-4), 9.14 (br d, 1H,
J¼3.9 Hz, H-2), 9.05 (s,1H, H-9), 8.73 (s,1H, H-6), 8.43 (br s, 2H, OH),
7.85 (dd, 1H, J¼3.9, 8.4 Hz, H-3), 7.43 (d, 2H, J¼8.0 Hz, Harom), 7.38
(d, 2H, J¼8.0 Hz, Harom), 4.71 (s, 2H, CH2); 13C NMR (126 MHz,
(500 MHz, CDCl3/DMSO-d6): d 9.50 (s, 1H, H-9), 9.47 (d, 1H,
J¼8.5 Hz, H-4), 9.18 (br s, 1H, H-2), 8.87 (s, 1H, H-6), 8.03 (br s, 2H,
OH), 7.73–7.72 (m, 1H, H-3), 7.33 (t, 2H, J¼7.3 Hz, Harom), 7.70–6.98
(m, 3H, Harom), 5.58 (s, 2H, CH2); 13C NMR (126 MHz, DMSO-d6):
DMSO-d6):
d 154.4, 150.6, 146.6, 145.6, 136.3, 135.5, 133.6, 133.0,
133.0, 132.0, 131.0 (q, JCF¼30.2 Hz), 129.6, 126.9, 124.8 (q,
JCF¼278.3 Hz), 124.1, 124.0 (q, JCF¼290.5 Hz), 123.7, 122.4, 94.6 (q,
JCF¼32.7 Hz), 35.1; IR (KBr, cmꢁ1): 3380, 3108; Anal. Calcd for
C22H13ClF6N2O2S: C, 50.93; H, 2.53; N, 5.40. Found: C, 51.00; H, 2.66;
N, 5.20.
d
157.8, 152.6, 150.1, 146.8, 145.1, 135.8, 135.1, 131.5 (q, JCF¼30.1 Hz),
129.6, 129.6, 126.5, 124.1 (q, JCF¼278.0 Hz), 123.5, 123.5 (q,
JCF¼291.8 Hz), 123.3, 121.6, 121.3, 114.8, 94.0 (q, JCF¼32.7 Hz), 65.7;
IR (KBr, cmꢁ1): 3313, 3128; Anal. Calcd for C22H14F6N2O3: C, 56.42;
H, 3.01; N, 5.98. Found: C, 56.46; H, 3.16; N, 5.79.
4.5.9. 2,2,2-Trifluoro-1-(8-(4-nitrophenylthiomethyl)-7-
trifluoromethyl[1,10]phenanthrolin-5-yl)ethane-1,1-diol (10i)
Compound 10i: 44%; mp 145–146 ꢀC (AcOEt); 1H NMR
4.6.4. 1-(8-(4-Chlorophenoxymethyl)-7-trifluoromethyl-
[1,10]phenanthrolin-5-yl)-2,2,2-trifluoroethane-1,1-diol (11d)
Compound 11d: 54%; mp 173–174 ꢀC (AcOEt); 1H NMR
(500 MHz, CDCl3/DMSO-d6):
d
9.37 (d, 1H, J¼7.1 Hz, H-4), 9.33 (s,
(500 MHz, DMSO-d6):
d
9.51 (s, 1H, H-9), 9.38 (d, 1H, J¼8.1 Hz, H-4),
1H, H-9), 9.16 (br s, 1H, H-2), 8.75 (s, 1H, H-6), 8.45 (br s, 2H, OH),
8.19 (d, 2H, J¼7.9 Hz, Harom), 7.86 (dd, 1H, J¼2.7, 7.1 Hz, H-3), 7.72 (d,
2H, J¼7.9 Hz, Harom), 4.94 (s, 2H, CH2); 13C NMR (126 MHz, CDCl3/
9.19 (br d, 1H, J¼3.8 Hz, H-2), 8.79 (s, 1H, H-6), 8.48 (br s, 2H, OH),
7.89 (dd, 1H, J¼3.8, 8.1 Hz, H-3), 7.41 (d, 2H, J¼7.9 Hz, Harom), 7.16 (d,
2H, J¼7.9 Hz, Harom), 5.62 (s, 2H, CH2); 13C NMR (126 MHz, DMSO-
DMSO-d6):
d
153.8, 150.2, 146.3, 145.4, 145.0, 144.8, 136.0, 135.2,
d6): d 156.8, 152.6, 150.2, 147.0, 145.1, 135.9, 135.2, 131.6 (q,
131.2 (q, JCF¼30.2 Hz), 130.2, 128.3, 126.6, 124.2 (q, JCF¼278.0 Hz),
124.0, 123.6, 123.5 (q, JCF¼289.3 Hz), 123.3, 122.0, 94.1 (q,
JCF¼32.7 Hz), 32.7; IR (KBr, cmꢁ1): 3379, 3116; Anal. Calcd for
JCF¼31.1 Hz), 129.4, 129.3, 126.6, 125.2, 124.2 (q, JCF¼278.0 Hz),
123.6, 123.5 (q, JCF¼290.5 Hz), 123.4, 121.7, 116.7, 94.1 (q,
JCF¼32.7 Hz), 66.2; IR (KBr, cmꢁ1): 3346, 3126; Anal. Calcd for

D. Shibata et al. / Tetrahedron 65 (2009) 6189–6195
6195
102, 193–202; (c) Efthimiadou, E. K.; Katsarou, M. E.; Karaliota, A.; Psomas, G.
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G.; Loriga, G.; Murineddub, G.; Pinnab, G. A. Tetrahedron Lett. 2003, 43, 3601–
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C22H13ClF6N2O3: C, 52.55; H, 2.61; N, 5.57. Found: C, 52.46; H, 2.82;
N, 5.45.
Acknowledgements
We would like to thank the Japan Society for the Promotion of
Science (JSPS) and the Centre National de la Recherche Scientifique
(CNRS) for support of this research, the Direction des Relations
Internationales (DRI) of the CNRS for travel funds (M.M.) and JSPS
for a research fellowship (M.M.).
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