Synthesis of 1,10-N,N′-phenanthroline dioxides using HOF·CH3CN complex

Article abstract of DOI:10.1021/jo047960e

(Chemical Equation Presented) HOF·CH₃CN, a very efficient oxygen-transfer agent, made readily from F₂, H₂O, and CH₃CN, was reacted with various 1,10-phenanthroline derivatives to form the corresponding N,N′-dioxides in good yields and short reaction times.

Full text of DOI:10.1021/jo047960e

Synthesis of 1,10-N,N′-Phenanthroline Dioxides Using HOF‚CH3CN
Complex
Mira Carmeli and Shlomo Rozen*
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University,
Tel-Aviv 69978, Israel
rozens@post.tau.ac.il
Received November 17, 2004
HOF‚CH3CN, a very efficient oxygen-transfer agent, made readily from F2, H2O, and CH3CN, was
reacted with various 1,10-phenanthroline derivatives to form the corresponding N,N′-dioxides in
good yields and short reaction times.
HOF‚CH3CN, considered to be the best oxygen-transfer
agent chemistry has to offer, is readily prepared by
bubbling dilute fluorine through aqueous acetonitrile. It
was previously used to hydroxylate sp3 tertiary carbon
centers, oxidize alcohols, ketones and ethers, as well as
transform aliphatic and aromatic amines, including
amino acids, into the corresponding nitro derivatives.1
This agent was also used for other oxygen-transfer
reactions such as olefins and aromatic ring epoxidations,2
transforming azides and vicinal diamines into the cor-
responding nitro and dinitro derivatives,3 and much
more.4
The family of 1,10-phenanthroline N,N′-dioxides is of
interest as a ligand in organometallic chemistry, as an
oxygen-transfer agent, and as a model for preparing of
higher heterohalicenes.5 Despite many attempts, com-
pounds of this family eluded chemists for more than 50
years6 since it proved to be extremely difficult to take
the three rings of the parent 1,10-phenanthroline (1a)
out of planarity, a prerequisite for accommodating the
two oxygen atoms in the bay area of the aromatic 2a.
We report here on the use of this reagent for constructing
such N,N′-dioxides from the parent 1,10-phenanthrolines
as a part of a new family which, not long ago, was
considered to be impossible to make.7
Result and Discussion
It took less than 2 min for 3 equiv of HOF‚CH3CN to
convert 5-chloro-1,10-phenanthroline (1b) to the N,N′-
dioxide (2b) in 67% yield (Scheme 1). It should be
mentioned that this is the only family member previously
synthesized, although the difficult oxidative step of the
aromatic phenanthroline system was avoided and the
aromatization to 2b was completed only after the N,N′-
dioxide moiety was constructed.8 Although HOF‚CH3CN
is known to react with aromatic rings,2a the reaction with
the nitrogen atoms is much faster and no difficulties were
encountered with the disubstituted 4,7-diphenyl-1,10-
phenanthroline (1c) that was transformed in 2 min using
4 equiv of HOF‚CH3CN to the N,N′-dioxide (2c) in 74%
yield. Increased substitution was also tolerated, and
when 3,4,7,8-tetramethyl-1,10-phenanthroline (1d) was
reacted with 5 equiv of HOF‚CH3CN, the N,N′-dioxide
(2d) was obtained in 3 min and 67% yield.
(1) (a) Rozen, S.; Brand, M.; Kol, M. J. Am. Chem. Soc. 1989, 111,
8325. (b) Rozen, S.; Bareket, Y.; Kol, M. Tetrahedron 1993, 49, 8169.
(c) Rozen, S.; Dayan, S.; Bareket, Y. J. Org. Chem. 1995, 60, 8267. (d)
Kol, M.; Rozen, S. J. Chem. Soc., Chem. Commun. 1991, 567. Rozen,
S.; Kol, M. J. Org. Chem. 1992, 57, 7342. (e) Rozen, S.; Bar-Haim, A.;
Mishani, E. J. Org. Chem. 1994, 59, 1208.
(2) (a) Kol, M.; Rozen, S. J. Org. Chem. 1993, 58, 1593. (b) Rozen,
S.; Golan, E. Eur. J. Org. Chem. 2003, 1915. (c) Golan, E.; Hagooly,
A.; Rozen, S. Tetrahedron Lett. 2004, 45, 3397.
We were interested to see whether the HOF‚CH3CN
could overcome the steric hindrance around the nitrogen
atoms. An interesting compound suitable for evaluation
(3) (a) Rozen, S.; Carmeli, M. J. Am. Chem. Soc. 2003, 125, 8118.
(b) Golan, E.; Rozen, S. J. Org. Chem. 2003, 68, 9170.
(4) (a) Rozen, S. Acc. Chem. Res. 1996, 29, 243. (b) Rozen, S. Pure
Appl. Chem. 1999, 71, 481.
(5) Katz, T. J. Angew. Chem., Int. Ed. 2000, 39, 1921.
(6) (a) Maerker, G.; Case, F. H. J. Am. Chem. Soc. 1958, 80, 2745.
(b) Corey, E. J.; Borror, A. L.; Foglia, T. J. Org. Chem. 1965, 30, 282.
(c) Wenkert, D.; Woodward, R. B. J. Org. Chem. 1983, 48, 283. (d)
Gillard, R. D. Inorgan. Chim. Acta 1981, 53, L173.
(7) For a preliminary report on the synthesis of the parent N,N′-
dioxide 2a, see: Rozen, S.; Dayan, S. Angew. Chem., Int. Ed. 1999,
38, 3471.
(8) Antkowiak, R.; Antkowiak, W. Z. Heterocycles 1998, 47, 893.
10.1021/jo047960e CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/11/2005
J. Org. Chem. 2005, 70, 2131-2134
2131

Carmeli and Rozen
SCHEME 1. Synthesis of 1,10-Phenanthroline
N,N′-Dioxides
SCHEME 2. Synthesis of 1,10-Phenanthroline
N,N′-Dioxides with [18]O Isotope
SCHEME 3. Oxidation of Dihidrophenanthrolines
of such a question seems to be the tetrasubstituted 2,9-
dimethyl-4,7-diphenyl-1,10-phenanthroline (1e).9 The out-
come of the reaction provided a positive answer, but an
excess of 12 equiv was needed for forming the N,N′-
dioxide (2e) in 2 min and 66% yield. It should be
mentioned that using only 1.2 equivalent of HOF‚CH3-
CN resulted in the mono N-oxide of 2,9-dimethyl-4,7-
diphenyl-1,10-phenanthroline (3e) in 93% yield after a
few seconds.
the best source for all oxygen isotopes. We have passed
fluorine through a solution of acetonitrile and H218O and
obtained H18OF‚CH3CN, which was reacted with either
1a or 3a (Scheme 2). In the first case, the MS (FAB) [m/z
) 217 (M + 1)+] clearly shows that 6, with both oxygen
atoms being [18]O isotopes, is obtained. In the case of
3a, compound 7 with only one [18]O was formed without
any scrambling of the oxygen atoms (MS (CI) [m/z ) 215
(M + 1)+]). Coupled with the previous results we can
conclude that 1,10 phenanthroline N,N′-dioxides has a
potential of serving as a source for molecular oxygen with
any isotope variation (Scheme 2).
While compounds 2 could not be obtained by reacting
the corresponding 1 with m-CPBA or dimethyl dioxirane
(DMDO), this was not the case with partially reduced
phenanthrolines that are not strictly planar. 5,8-Dimeth-
yl-6,7-dihydro-dibenzo[b,j][1,10]phenanthroline (4) can
serve as an example. Although quite sterically hindered
around the nitrogen atoms, treating it for more than 6 h
with an excess of m-CPBA in boiling methylene chloride
produced the N,N′-dioxide (5) in 63% yield. Similarly, 5
was obtained in 24% yield by reacting 4 with 20 equiv of
dimethyldioxirane (DMDO) for 6 h. Reacting 4, however,
with 9 equivalents of HOF‚CH3CN furnished 5 in higher
than 90% yield in only 2 min reaction carried at room
temperature (Scheme 3).
A less reactive, electron-deficient 4-nitro-1,10-phenan-
throline (1f) was also reacted. Although the yield was
somewhat lower, the N,N′-dioxide (2f) was still obtained
in 47% yield after 3 min using 6-equiv of HOF‚CH3CN.
Compared to the parent phenanthrolines, the UV
spectra of all N,N′-dioxides exhibit a red shift of up to
75 nm and with somewhat lower ꢀ. The main reason for
these phenomena seems to be the electrostatic repulsion
between the nonbonding electron pairs of the oxygen
atoms which are in close proximity.7 Such a repulsion
increases the electron density of the core and enables an
easier n f π* transition with characteristic lower ꢀ.
Upon heating these dioxides to their melting or de-
composition point, the two oxygen atoms were expelled
and the parent phenanthrolines were obtained in yields
of up to 30%. It was of interest to find out whether the
two oxygen atoms released from 2a for example, com-
bined to form molecular oxygen. We heated this com-
pound to its melting point (210 °C) in nitrogen atmo-
sphere containing an inner capillary tube, loaded with
Et2Zn. After a few seconds, the Et2Zn lost its clarity and
started to smoke, indicating that molecular oxygen was
indeed evolved. In a control experiment where the parent
phenanthroline 1a was melted, no gases were evolved
and the Et2Zn remained clear.
One of the main reasons for the persisting 50 years
search for ways to make the family of the 1,10-phenan-
throline N,N′-dioxides was to examine their complexation
ability to metals and potential role as ligands in orga-
nometallic chemistry. As a test case we chose to react
2d with europium tris[3-(trifluoromethylhydroxymeth-
ylene)-(+)-camphorate]-Eu(tfc)3 since it is easy to follow
One of the advantages of the HOF‚CH3CN complex is
that its electrophilic oxygen comes from water, which is
1
the complexation by H NMR (Scheme 4). The shift of
H-2 and H-9 (+1 ppm: from 8.42 to 9.42 ppm) as well as
the shift of the two hydrogens at 5 and 6 (+ 0.71 ppm:
(9) Ono, K.; Yanase, T.; Ohkita, M.; Saito, K.; Matsushita, Y.; Naka,
S.; Okada, H.; Onnagawa, H. Chem. Lett. 2004, 33, 276.
2132 J. Org. Chem., Vol. 70, No. 6, 2005

Synthesis of 1,10-N,N′-Phenanthroline Dioxides
inert gases are commercially available, simplifying the process.
If elementary precautions are taken, work with fluorine is
relatively simple, and we had no bad experiences working with
it.
SCHEME 4. Complexation of Phenanthroline
Dioxide Derivative with a Metal
General Procedure for Producing HOF‚CH3CN. Mix-
tures of 10-20% F2 with nitrogen were used in this work. The
gas mixture was prepared in a secondary container before the
reaction was started. It was then passed at a rate of about
400 mL/min through a cold (-15 °C) mixture of 100 mL of CH3-
CN and 10 mL of H2O. The development of the oxidizing power
was monitored by reacting aliquots with an acidic aqueous
solution of KI. The liberated iodine was then titrated with
thiosulfate. Typical concentrations of the oxidizing reagent
were around 0.4-0.6 M.
General Procedure for Working with HOF‚CH3CN.
1,10-Phenanthroline derivative was dissolved in CHCl3, and
the mixture was cooled to 0 °C. The oxidizing agent was then
added in one portion to the reaction vessel. The excess of HOF‚
CH3CN was quenched with saturated sodium bicarbonate and
extracted with CHCl3, and the organic layer dried over MgSO4.
Evaporation of the solvent followed by recrystallization gave
the corresponding 1,10-phenanthroline N,N′-dioxide.
4,7-Diphenyl-1,10-phenanthroline N,N′-dioxide (2c)
was prepared from 1c (1gr, 3 mmol) as describe above resulting
in a 74% yield of an orange solid recrystallized from EtOH/
CH2Cl2 (2/1): mp ) 230-231 °C; IR 663, 702, 780, 820, 1183,
1295, 1373, 1433, 2989 cm-1; UV-vis (CHCl3) λmax 254 (ꢀ )
4.5 × 104), 270 (ꢀ ) 3.6 × 104), 300 (ꢀ ) 2.6 × 104), 376 nm (ꢀ
from 7.77 to 8.48 ppm) reached a plateau after the
addition of 1.2 equiv of the Eu agent. The identical shift
of the symmetrical hydrogens as well as the fact that
adding an excess of Eu(tfc)3 did not change the outcome
mean that the metal complexed itself with the two oxygen
atoms of the same molecule, a feature which did not
change even after 5 h. An additional reason for working
with Eu(tfc)3 was to see if we could observe a separate
set of peaks for each enantiomer of the helical 2d. We
were not able to see such diastereoisomeric separation
1
) 0.8 × 104); H NMR 7.42-7.53 (2 H, m), 7.61 (2 H, s), 8.62
ppm (2 H, d, J ) 6.6 Hz); 13C NMR 123.9, 125.7, 128.7, 128.9,
129.7, 130.5, 134.2, 135.5, 136.6, 138.4 ppm; GC/MS m/z ) 364
(M)+.10 Anal. Calcd for C24H16N2O2: C, 79.11; H, 4.43; N, 7.69.
Found: C, 78.95; H, 4.56; N, 7.71.
1
by either H or 19F NMR. It is possible that there is a
rapid inversion of the two N-O groups, but it should be
emphasized that even at low temperatures of about -60
°C only one set of signals in both 1H and 19F spectra was
observed.
In conclusion, HOF‚CH3CN, is unique in its ability to
construct a whole new family of 1,10-phenanthroline
N,N′-dioxides from the corresponding 1,10-phenanthro-
lines. Among other features these compounds have a
potential of becoming a new family of ligands in organo-
metallic chemistry.
We hope that this work will encourage chemists not
to shy away from F2 because of some unjustified fears
and prejudice. Reactions with HOF‚CH3CN can provide
a good example. Today, prediluted fluorine is com-
mercially available and the work with it is relatively easy.
All reaction vessels are standard glassware, and a simple
basic trap takes care of small amounts of F2 which had
not reacted with water.
3,4,7,8-Tetramethyl-1,10-phenanthroline N,N′-dioxide
(2d) was prepared from 1d (1.1 gr, 4.7 mmol) as described
above resulting in a 67% yield of a yellow solid decomposing
at 300 °C: IR 666, 734, 761, 782, 1303, 3020 cm-1; UV-vis
(CHCl3) λmax 245 (ꢀ ) 2.1 × 104), 281 (ꢀ ) 2.1 × 104), 398 nm
1
(ꢀ ) 0.12 × 104); H NMR 2.42 (6 H, s), 2.57 (6 H, s), 7.81 (2
H, s), 8.44 ppm (2 H, s); 13C NMR 14, 17.3, 123.7, 129.5, 130.8,
132.6, 133.3, 139.2 ppm; HRMS (CI) m/z ) calcd 269.129114,
found 269.29114 (M + 1)+. Anal. Calcd for C16H16N2O2‚
1/2H2O: C, 69.31; H, 6.13; N, 10.10. Found: C, 68.92; H, 5.92;
N; 9.96.
2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline N,N′-
dioxide (2e) was prepared from 1e (0.9 gr, 2.5 mmol) as
described above resulting in a 66% yield of an orange solid
recrystallized from EtOH and decomposing at 215 °C: IR 704,
735, 765, 778, 790, 1301, 3018 cm-1; UV-vis (CHCl3) λmax 253
(ꢀ ) 2.8 × 104), 298 (ꢀ ) 1.4 × 104), 349 (ꢀ ) 0.9 × 104), 392
nm (ꢀ ) 0.4 × 104); 1H NMR 2.82 (6 H, s), 7.44-7.55 ppm (14
H, m); 13C NMR 18.2, 124.6, 128.4, 128.7, 129.1, 129.8, 133.2,
135.4, 137, 148 ppm. Anal. Calcd for C26H20N2O2: C, 79.57;
H, 5.14; N, 7.14. Found: C, 78.97; H, 5.40; N, 7.23.
Experimental Section
1H NMR and 13C NMR were obtained at 400 MHz, with
CDCl3 as the solvent and Me4Si as an internal standard. IR
spectra were recorded in a CHCl3 solution on an FTIR
spectrophotometer. MS spectra were measured under CI, EI,
or FAB conditions. In extreme cases where no conventional
instrument was able to detect the molecular ions, they were
successfully detected by Amirav’s supersonic GC-MS, devel-
oped in our department.10 UV spectra were recorded in CHCl3
and EtOH serving as solvents.
General Procedure for Working with Fluorine. Fluo-
rine is a strong oxidant and very corrosive material. It should
be used only with an appropriate vacuum line.11 For the
occasional user, however, various premixed mixtures of F2 in
2,9-Dimethyl-4,7-diphenyl-1,10-phenanthroline mon-
oxide (3e) was prepared from 1e (0.7 gr, 1.9 mmol) as
described above resulting in a 93% yield of a yellow solid: mp
) 236-240 °C; IR 700, 704, 734, 759, 780, 1292, 3020 cm-1
;
UV-vis λmax (CHCl3) 259 (ꢀ ) 2.9 × 104), 285 (ꢀ ) 3.3 × 104),
344 (ꢀ ) 1.05 × 104), 402 nm (ꢀ ) 0.2 × 104); 1H NMR 2.84 (3
H, s), 2.99 (3 H, s), 7.55-7.48 (12 H, m), 7.67 (1 H, d, J ) 5
Hz), 7.71 ppm (1 H, d, J ) 5 Hz); 13C NMR 19.5, 25.9, 123.3,
123.9, 124.6, 125.1, 125.3, 128.3, 128.4, 128.5, 128.6, 129.3,
129.7, 129.8, 135.9, 137.7, 137.9, 138, 142.7, 148.2, 149.4, 157.4
ppm; MS (FAB) m/z ) 377.1 (M + 1)+. Anal. Calcd for
C26H20N2O‚H2O: C, 78.79; H, 5.48; N, 7.19. Found: C, 79.41;
H, 5.61; N, 7.25.
5-Nitro-1,10-phenanthroline N,N′-dioxide (2f) was pre-
pared from 1f (1 gr, 4.5 mmol) as described above resulting in
a 47% yield of a brown solid, recrystallized from H2O and
decomposing at 200 °C: IR 670, 726, 748, 765, 794, 1215, 1541,
1603, 3029 cm-1; UV-vis (MeOH) λmax 233 (ꢀ ) 1.5 × 104),
(10) (a) Dagan, S.; Amirav, A. J. Am. Soc. Mass. Spectrom. 1996, 7,
550. (b) Fialkov, A. B.; Amirav, A. Rapid Commun. Mass Spectrom.
2003, 17, 1326.
(11) Dayan, S.; Kol, M.; Rozen, S. Synthesis 1999, 1427.
J. Org. Chem, Vol. 70, No. 6, 2005 2133

Carmeli and Rozen
258 (ꢀ ) 1.0 × 104), 343 (ꢀ ) 0.3 × 104); 1H NMR 7.59 (1 H, dd,
J1 ) 4 Hz, J2 ) 3 Hz), 7.61 (1 H, dd, J1 ) 4 Hz, J2 ) 3 Hz),
7.82 (1 H, d, J ) 4 Hz), 8.21 (1 H, d, J ) 4 Hz), 8.46 (1 H, s),
8.56 (1 H, d, J ) 3 Hz), 8.58 ppm (1 H, d, J ) 3 Hz); 13C NMR
122, 127.5, 127.8, 128.2, 128.4, 128.6, 129.5, 132.6, 132.9,
142.9, 144.7 ppm; MS (CI) m/z ) 258 (M + 1)+.
6,7-Dihydro-5,8-dimethyldibenzo[b,j][1,10]phen-
anthroline N,N′-dioxide (5) was prepared from 4 (1.2gr, 3.9
mmol) as described above resulting in an 90% yield of yellow
solid, recrystallized from CHCl3 and decomposing at 200-201
°C: IR 669, 726, 748, 779, 1231, 1357, 3026 cm-1; UV-vis
(CHCl3) λmax 247 (ꢀ ) 2.5 × 104), 344 (ꢀ ) 1.0 × 104), 377 nm
(ꢀ ) 0.9 × 104); 1H NMR 2.66 (6 H, s), 2.72 (2 H, d, J ) 5 Hz),
3.39 (2 H, d, J ) 5.5 Hz) 7.67-7.76 (4 H, m), 8.04 (2 H, d, J )
4 Hz), 8.92 ppm (2 H, d, J ) 4 Hz); 13C NMR δ 15.9, 28.1,
122.3, 126.3, 128.6, 130.7, 131.1, 131.2, 134.5, 138.4, 143 ppm;
MS (FAB) m/z ) 343 (M + 1)+. Anal. Calcd for C22H18N2O2‚
1/2H2O: C, 76.18; H, 5.90; N, 8.10. Found: C, 75.99; H, 6.07;
N, 7.39.
JO047960E
2134 J. Org. Chem., Vol. 70, No. 6, 2005