New nonsymmetric phenanthrolines as very effective ligands in the palladium-catalyzed carbonylation of nitrobenzene

Article abstract of DOI:10.1021/om100023x

Inspired by the results of a previous mechanistic study, a series of mostly new nonsymmetric phenanthrolines were synthesized and tested as ligands in the palladium-catalyzed reductive carbonylation reaction of nitrobenzene to methyl phenylcarbamate. Very good results were obtained when the asymmetry was of an electronic nature (a donating substituent in the para position of one of the two pyridinic rings and an electron-withdrawing or no substituent on the para position of the other pyridinic ring), but steric hindrance in the ortho or meta position retarded the reaction. The TOF for the modified system is the highest ever reported for any carbonylation reaction of nitroarenes.

Full text of DOI:10.1021/om100023x

Organometallics 2010, 29, 1465–1471 1465
DOI: 10.1021/om100023x
New Nonsymmetric Phenanthrolines as Very Effective Ligands in the
Palladium-Catalyzed Carbonylation of Nitrobenzene
Francesco Ferretti, Fabio Ragaini,* Roberta Lariccia, Emma Gallo, and Sergio Cenini
ꢀ
Universita di Milano, Dipartimento di Chimica Inorganica, Metallorganica e Analitica “Lamberto Mala-
testa”, ISTM-CNR, and INSTM, UdR Milano, Via Venezian 21, 20133 Milano, Italy
Received January 7, 2010
Inspired by the results of a previous mechanistic study, a series of mostly new nonsymmetric
phenanthrolines were synthesized and tested as ligands in the palladium-catalyzed reductive
carbonylation reaction of nitrobenzene to methyl phenylcarbamate. Very good results were obtained
when the asymmetry was of an electronic nature (a donating substituent in the para position of one of
the two pyridinic rings and an electron-withdrawing or no substituent on the para position of the
other pyridinic ring), but steric hindrance in the ortho or meta position retarded the reaction. The
TOF for the modified system is the highest ever reported for any carbonylation reaction of
nitroarenes.
Introduction
carbamates can be obtained more easily and with a high
selectivity (eq 1):
The carbonylation of organic nitro compounds is a process
with a high potential synthetic and industrial interest, since
many products can be obtained from nitro compounds and
CO, including isocyanates, carbamates, and ureas.1-3 Ureas
and carbamates are important final products and inter-
mediates in the synthesis of pesticides, fertilizers, and dyes,
and mono- and diisocyanates are important intermediates
in the manufacturing of pesticides, polyurethane foams,
plastics, synthetic leather, adhesives, and coatings. Further-
more, the urea functionality is also present in several pharma-
ceutical candidates.4
cat:
s
ArNO þ ROH þ 3CO
ArNHCOOR þ 2CO2 ð1Þ
2
If no alcohol is added, but at least an equimolar amount of
aromatic amine with respect to the nitroarene is present,
diarylureas are produced (eq 2).
cat:
s
ArNO þ ArNH þ 3CO
ArNHCðOÞNHAr þ 2CO2
ð2Þ
2
2
The classical method for the production of isocyanates
requires the intermediate reduction of the nitro compound
to amine, followed by reaction with phosgene. However,
phosgene is a very toxic and corrosive material. Recently
(2006), a large plant producing toluenediisocyanate (TDI)
was shut in Italy mainly because of the pressure from the
local population and authorities against the use of phos-
gene close to a populated area. Thus, it is not surprising that
an enormous effort has been applied to the development of
phosgene-free routes to isocyanates. Among these, the
catalytic carbonylation of nitro compounds, particularly
of aromatic ones, represents one of the most interesting
alternatives, but the direct carbonylation of nitro com-
pounds to the corresponding isocyanates has proved to be
a difficult reaction. However, in the presence of an alcohol,
At high temperature, diarylureas react with alcohols when
the latter are employed as solvents to afford carbamates and
arylamines (eq 3).
ArNHCðOÞNHAr þ ROH
ArNHCOOR þ ArNH
s
2
ð3Þ
Diarylureas are intermediately formed during the reaction
even when alcohols are present.5 Both carbamates and ureas
are important industrial products themselves, but can also be
thermally cracked to the corresponding isocyanates, thus
providing a phosgene-free route to these important inter-
mediates (eq 4).
ArNHCOOR
or
ROH
or
Δ
s
ArNCO þ
ð4Þ
ArNHCðOÞNHAr
ArNH2
*Corresponding author. Phone: (þ39)0250314373. Fax: (þ39)
0250314405. E-mail: fabio.ragaini@unimi.it.
(1) Cenini, S.; Ragaini, F. Catalytic Reductive Carbonylation of
Organic Nitro Compounds; Kluwer Academic Publishers: Dordrecht, The
Netherlands, 1996.
(2) Tafesh, A. M.; Weiguny, J. Chem. Rev. 1996, 96, 2035–
2052.
In recent years, the catalytic system based on palladium-
phenanthroline complexes has emerged as the most active
and promising for a possible industrial application, and new
(3) Paul, F. Coord. Chem. Rev. 2000, 203, 269–323.
(4) Diaz, D. J.; Darko, A. K.; McElwee-White, L. Eur. J. Org. Chem.
2007, 4453–4465.
(5) Ragaini, F.; Gasperini, M.; Cenini, S.; Arnera, L.; Caselli, A.;
Macchi, P.; Casati, N. Chem.;Eur. J. 2009, 15, 8064–8077.
r
2010 American Chemical Society
Published on Web 02/24/2010
pubs.acs.org/Organometallics

1466 Organometallics, Vol. 29, No. 6, 2010
Ferretti et al.
Scheme 1
synthesis of the employed ligands, several of which had never
been reported in the literature before.
Results and Discussion
Phenanthrolines Synthesis. As mentioned in the Introduc-
tion, the mechanistic study had suggested that nonsymmetric
phenanthrolines may be better ligands than symmetric ones
because they may more easily detach a nitrogen atom from
the metal. Specifically, the best phenanthrolines should have
a donating substituent on one of the two pyridine rings, so
that complete detachment is minimized, and bear either an
electron-withdrawing or no substituent on the other. The
range of suitable substituents of either kind is not wide
because it must be considered that the substituent should
be inert under the forcing reaction conditions, 170 °C in
methanol, and in the presence of the palladium catalyst.
Moreover, the substituent should not compete with the
nitrogen atom itself for coordination to palladium.
Among donor substituents, alkyl and alkoxy groups
should be suitable. Dialkylamino groups are potentially
useful, but they are also quite basic, and the presence of an
excess of acidic promoter may result in their partial protona-
tion, inverting their polarity. Thus they were not considered
at the moment.
Among electron-withdrawing groups, halogens are surely
not suitable because independent research in our group has
shown that bromine- and chlorine-substituted pyridines
oxidatively add to palladium when the same precatalyst
employed in this study is used under similar carbonylation
conditions.15 The nitro group would clearly be carbonylated
during the reaction conditions and must be discarded. The
-CF3 group may be suitable, but no phenanthroline bearing
this substituent at the 4 or 7 positions has been reported in
the literature, and several attempts to prepare such com-
pounds in our group gave complex product mixtures. We
thus chose the ester group as the most promising candidate,
although the cyano group will also be tested in the future.
Since detachment of one nitrogen atom can also be caused by
steric hindrance, 2-methylphenanthroline, 2,9-dimethylphe-
nanthroline, and 3-tert-butylphenanthroline were also tested.
The desired phenanthrolines were obtained by combining
or adapting reactions previously reported in the literature.
Among the synthesized ligands, only the 4-methyl and the
2-methyl derivatives had been previously fully described.
Note that 3-ethylphenanthroline had been reported in a very
old paper,16 but no spectroscopic characterization was avail-
able at the time and the compound has not been reported
again.
modifications continue to be reported.6 We have much
improved its efficiency by employing phosphorus acids as
promoters.7-12
Very recently, we have published the results of an extensive
mechanistic study on this catalytic system.5 The results that
are most relevant to the present paper are the following:
(1) During the reaction the nitroarene is intermediately
reduced to arylamine, which is then carbonylated to aryliso-
cyanate.
(2) The metal species responsible for the latter reaction is a
bis-alkoxycarbonyl complex (1a in Scheme 1). The reaction
proceeds by the initial formation of a CO adduct, which is
present at equilibrium in only a very low relative amount in
the case of 2a. Arylamine attack on the coordinated CO and
acid-assisted proton transfer results in isocyanate forma-
tion. This pathway bears many similarities to the reactions
involved in the related oxidative carbonylation of amines,
which is another alternative to the use of phosgene for the
synthesis of isocyanates.13
(3) Formation of 2a could only be inferred by kinetic data,
but the corresponding complex with 2,9-dimethylphenan-
throline (neocuproine, 2,9-Me2Phen) and two chlorine
atoms respectively in place of phenanthroline and the alko-
xycarbonyl groups, 2b, could be characterized by X-ray
diffraction.5 Interestingly, 2b was found not to be a penta-
coordinate complex, but is indeed best seen as a slightly
distorted square-planar complex in which one of the two
nitrogen atoms of the ligand has detached.
The detachment of one of the two nitrogen atoms of the
phenanthroline has important chemical consequences, because
it is very likely that the same will occur during the catalytic cycle,
at least in our system. The detachment of one nitrogen atom also
suggests that hemilabile ligands may be more appropriate
ligands than symmetrical phenanthrolines for the catalytic
carbonylation reaction of nitroarenes. We thus decided to
explore this possibility. Since no nonsymmetric phenanthroline
was commercially available at the start of this study14 and few
have been reported in the literature, the work also involved the
The synthetic strategies employed are shown in
Schemes 2-4.
(6) Yang, Q.; Robertson, A.; Alper, H. Org. Lett. 2008, 10, 5079–
5082.
(7) Ragaini, F.; Cognolato, C.; Gasperini, M.; Cenini, S. Angew.
Phenanthrolines having one alkyl substituent on one
pyridine ring and none on the other (Scheme 2) were pre-
pared by reaction of commercially available 8-aminoquino-
line with the required unsaturated aldehyde or ketone in 70%
H2SO4 and in the presence of NaI, following the general
protocol described by O’Murchu17 and Bernhard.18
Chem., Int. Ed. 2003, 42, 2886–2889.
(8) Ragaini, F.; Gasperini, M.; Cenini, S. Adv. Synth. Catal. 2004,
346, 63–71.
(9) Gasperini, M.; Ragaini, F.; Cazzaniga, C.; Cenini, S. Adv. Synth.
Catal. 2005, 347, 105–120.
(10) Gasperini, M.; Ragaini, F.; Remondini, C.; Caselli, A.; Cenini, S.
J. Organomet. Chem. 2005, 690, 4517–4529.
(11) Gasperini, M.; Ragaini, F.; Cenini, S.; Gallo, E.; Fantauzzi, S.
Appl. Organomet. Chem. 2007, 21, 782–787.
(12) See ref 5 for a comprehensive list of all papers published on this
catalytic system.
(15) Ragaini, F.; Rapetti, A.; Visentin, E.; Monzani, M.; Caselli, A.;
Cenini, S. J. Org. Chem. 2006, 71, 3748–53.
(16) Case, F. H.; Jacobs, Z. B.; Cook, R. S.; Dickstein, J. J. Org.
Chem. 1957, 22, 390–393.
(13) Ragaini, F. Dalton Trans. 2009, 6251–6266.
(14) 4-Methylphenanthroline is presently commercially supplied by
Aldrich.
(17) O’Murchu, C. Synthesis 1989, 880–82.
(18) Belser, P.; Bernhard, S.; Guerig, U. Tetrahedron 1996, 52, 2937–
2944.

Article
Organometallics, Vol. 29, No. 6, 2010 1467
Scheme 2
hydroxyphenanthroline in refluxing diphenyl ether, similarly
to that reported for the symmetrical 4,7-dihydroxyphenan-
throline.21 Treatment of 8-hydroxyphenanthroline with
POCl3 affords the chloride derivative. This compound has
been previously obtained by other routes,22,23 but no spectral
characterization has been reported in the literature. Use of
POCl3 as chlorinating agent for this reaction has been
reported to give better yields than the previously employed
PCl5/PCl3 mixture.24,25
For the synthesis of the more complex 4-carbomethoxy-7-
methyl-1,10-phenanthroline, both the aforementioned stra-
tegies were employed (Scheme 4). Moreover, to differentiate
the two halves of the molecule, the strategy of Bernhard and
co-workers18 was employed. Starting from 2-aminoanisole,
8-methoxy-4-methylquinoline was first prepared by reaction
with vinyl methyl ketone as previously described. The meth-
oxy group was then hydrolyzed and substituted by an amino
one by a Bucherer reaction. With respect to the original
procedure,18 we more conveniently employed a pressure tube
instead of an autoclave in this step. The second ring was
prepared by use of Meldrum’s acid similarly to that described
above.
Scheme 3
Preliminary tests had evidenced that carbonylation of
4-chloropyridine proceeds in low yields, but, as expected,
the corresponding bromine derivative is carbonylated more
efficiently. Bromination of hydroxyphenanthrolines has
been reported to be best performed in molten POBr3.21,25
Since the latter is a quite expensive reagent and needs to be
used in very large amounts if the published procedure is
followed, we tested also the use of 1:1 by molar mixtures of
POBr3 and the much cheaper PBr3. This mixture gave
comparable results to pure POBr3, at least for our substrate.
Finally, carbonylation of 4-bromo-7-methylphenanthro-
line was performed in an autoclave employing Pd(dba)2 as
catalyst, with 1,3-bis(diphenylphosphino)propane (DPPP)
as a ligand. The obtained ligand was purified by column
chromatography, despite the fact that it was quite pure from
the beginning, to be sure that any trace of palladium had
been removed. This is important for the following tests,
since, as we will see, a large excess of ligand is employed
and any trace of palladium present in the ligand would
sensibly alter the effective metal loading in the catalytic
reaction.
Scheme 4
Catalytic Tests for the Comparison of Different Phenan-
throlines. It is generally observed that when catalytic systems
based on the use of neutral bidentate nitrogen ligands are
employed, better results are obtained by adding an excess of
free ligands in solution. This is especially true when working
at high temperatures and low catalyst loading, because
detachment of the ligand becomes very easy under these
conditions, and if recombination is not fast, catalyst deacti-
vation usually occurs. The best molar excess varies widely
(from a few mol % to a 500-fold molar excess or even more)
with the experimental conditions, but also with the identity
of the ligand. A reliable comparison cannot be performed at
just one ligand/metal ratio, but individual ligand ratio/
activity curves must be determined for each ligand and their
The introduction of a methoxy group was achieved by
substitution of a chloride substituent, analogously to that
known for the preparation of 4,7-dimethoxyphenanthro-
line.19,20 4-Chlorophenanthroline itself was prepared by
adapting a reaction scheme originally developed for the
symmetrical disubstituted derivative (Scheme 3). 8-Amino-
quinoline was initially treated with Meldrum’s acid in tri-
methyl orthoformate to give an adduct that cyclizes to the
(22) Snyder, H. R.; Freier, H. E. J. Am. Chem. Soc. 1946, 68, 1320–
(19) Wehman, P.; Kaasjager, V. E.; Delange, W. G. J.; Hartl, F.;
Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Fraanje, J.; Goubitz, K.
Organometallics 1995, 14, 3751–3761.
1322.
(23) Corey, E. J.; Borror, A. L.; Foglia, T. J. Org. Chem. 1965, 30,
288–90.
(20) Altman, R. A.; Buchwald, S. L. Org. Lett. 2006, 8, 2779–2782.
(21) Graf, G. I.; Hastreiter, D.; Everson a Silva, L.; Rebelo, R. A.;
Montalban, A. G.; McKillop, A. Tetrahedron 2002, 58, 9095–9100.
(24) Bell, T. W.; Hu, L. Y.; Patel, S. V. J. Org. Chem. 1987, 52, 3847–
50.
(25) Schmittel, M.; Ammon, H. Eur. J. Org. Chem. 1998, 785–792.

1468 Organometallics, Vol. 29, No. 6, 2010
Ferretti et al.
Figure 2. Nitrobenzene conversion for catalytic tests using
methoxy-substituted phenanthrolines as ligands.
Figure 1. Nitrobenzene conversion for catalytic tests using
methyl-substituted phenanthrolines as ligands.
maxima compared. Though this is much more experimen-
tally demanding, it is the only safe mode of assessing the
superiority of a ligand with respect to another.
We have performed a series of carbonylation reactions of
nitrobenzene working at a very high catalytic ratio, 15 200
(or 6.58 ꢀ 10-3 mol %), in order to avoid approaching com-
plete conversion even with the more active systems. All
conditions were kept constant except for the ligand identity
and the ligand/palladium ratio.
Apart from the phenanthrolines whose synthesis has been
described above, several symmetrical phenanthrolines were
also tested for comparison: phenanthroline (Phen), 4,7-
dimethylphenanthroline (4,7-Me2Phen), 4,7-dimethoxyphe-
nanthroline (4,7-(MeO)2Phen), 3,4,7,8-tetramethylphenan-
throline (3,4,7,8-Me4Phen), and 2,9-dimethylphenanthroline
(neocuproine, 2,9-Me2Phen).
Figure 3. Nitrobenzene conversion for catalytic tests using 3-
alkyl-substituted phenanthrolines as ligands.
agent, as previously described.7,8,26,27 In general, the reagent
concentrations are those previously optimized for unsubsti-
tuted phenanthroline.8 With the obvious exception of the
ligand identity and amount, only the catalyst concentration
was decreased, to allow a better comparison between diffe-
rent reactions. In all cases, [Pd(Phen)2][BF4]2 was employed
as catalyst. Although this means that two equivalents of the
unsubstituted ligand are always present, the ideal ligand/Pd
ratios are in the range 50-200, making the small amount of
unsubstituted ligand negligible with respect to the much
larger amount of substituted one. Ligand exchange is surely
not a problem, since it occurs easily even at room tempera-
ture and is surely very fast at the reaction temperature
(170 °C). It should be recalled that during the reaction
diphenylurea is intermediately accumulated, which cannot
be detected by gas chromatography and is later alcoholyzed,
yielding methyl phenylcarbamate and aniline. The latter re-
enter the catalytic cycle. Thus selectivity values for carba-
mate after short reaction times, such as those reported in the
tables, should not be taken as an indication of the actual
selectivity of the reaction, which would be much higher for
longer reaction times. The only indirect quantitative measure
of the selectivity is given by the amount of azo- and azoxy-
benzene formed, since these are only very slowly converted
Results are reported in Table S1 (Supporting Informa-
tion), and the turnover frequency values for nitrobenzene
conversion are shown graphically in Figures 1-3, while a
comprehensive larger scale figure in color and a plot compar-
ing all symmetrical and nonsymmetrical para-substituted
phenanthrolines are reported in the Supporting Information.
The TOF values, calculated over the full reaction time, are a
good indication of the reaction rate, as we have previously
shown that the kinetics is zero-order in nitrobenzene con-
centration and there is essentially no induction time when a
small amount of aniline is added at the beginning,5,7,8 as
always done for the reactions reported in this paper. The data
for phenanthroline were included in all figures to make a
comparison with the nonsymmetric analogues easier. All
reactions were performed in the presence of a small amount
of initially added aniline (ca. 2.6 mol % with respect to
nitrobenzene) and with phosphoric acid as promoter. 2,2-
Dimethoxypropane was also added as an internal drying
(26) Santi, R.; Romano, A. M.; Panella, F.; Mestroni, G.; Sessanta o
Santi, A. J. Mol. Catal. A: Chem. 1999, 144, 41–45.
(27) Santi, R.; Romano, A. M.; Panella, F.; Santini, C. J. Mol. Catal.
A: Chem. 1997, 127, 95–99.

Article
Organometallics, Vol. 29, No. 6, 2010 1469
into the desired product. For this reason, we will focus in the
following on conversion values, since these are the most
discriminating factors among the ligands.
same catalytic system by van Leeuwen.19 Indeed, in the latter
work no acid had been added.
Among symmetrical phenanthrolines, the only one con-
sistently giving better results than phenanthroline itself is
4,7-dimethylphenanthroline. This is also in accord with the
results by van Leeuwen.19
The results are very interesting. In most cases, the activity
shows a sharp increase when the concentration of the ligand
is increased up to an optimal value, followed by a much
slower decrease when this value is exceeded. The only
phenanthroline that completely inhibits any catalytic activity
is 2,9-Me2Phen (Figure 1), but a strongly inhibiting effect is
exerted even by just one methyl group ortho to a phenanthro-
line nitrogen, and the activity observed with 2-methylphe-
nanthroline is very low (Figure 1).
The most rewarding observation, with respect to the
theoretical premises, is that unencumbered nonsymmetrical
phenanthrolines always gave higher maximum activities
compared to their symmetrical counterparts. Specifically,
4-methylphenanthroline gave a higher activity than both
phenanthroline and 4,7-dimethylphenanthroline, and the
effect is even larger when comparing 4-methoxyphenanthro-
line with phenanthroline and 4,7-dimethoxyphenanthroline.
4-Carbomethoxy-7-methylphenanthroline also gave a better
performance than 4,7-dimethylphenanthroline, but the sym-
metrical phenanthroline with two -COOMe groups was not
prepared. 3-Ethylphenanthroline gave a maximum activity
essentially indistinguishable from that of phenanthroline,
but the maximum was shifted at much lower ligand/Pd ratios
(35 instead of 150, Figure 3), which is itself an advantage
from a practical point of view. The more hindered 3-tBuPhen
gave worse results, confirming the negative effect of steric
hindrance even in the meta position of the pyridinic ring
(Figure 3).
Among symmetrical phenanthrolines, 3,4,7,8-Me4Phen
(Figure 1) and 4,7-dimethoxyphenanthroline (Figure 2)
show an atypical behavior, with the activity having a
small plateau at intermediate ligand/Pd ratios, followed by
a further rate increase. Such behavior seems at first sight
suspect, but it should be noted that these two phenanthro-
lines are the two most basic among those tested and the
deviation from the behavior observed for the other ligands
may have a specific explanation. We recall that an acid is
present in the reaction mixture, and we have recently shown
that the protonation equilibrium is not completely shifted
toward the reagents even when diphenylphosphinic acid and
phenanthroline are used. Phosphoric acid is stronger than
diphenylphosphinic acid, and in the case of the most basic
ligands it is possible that protonation becomes more impor-
tant, altering all the equilibria in the system. An indirect
support for this explanation comes from the change in the
selectivity of the reaction toward the byproduct azoxyben-
zene as the ligand/Pd ratio is varied. It has been previously
noted that the addition of acids to the reaction mixture
causes a decrease in the amount of the formed azoxyben-
zene.7-10,28 The selectivity trends observed in this work
(Table S1) indicate that an increase in azoxybenzene selecti-
vity is observed at higher ligand ratios, in accord with a
partial neutralization of the acid by the excess ligand. How-
ever, whereas the effect is small in most cases (e.g., the
selectivity changes from 1.9% to 2.8% along the series in
the case of unsubstituted phenanthroline), it is larger in the
case of the two aforementioned phenanthrolines (from 2.8%
to 5.1% in the case of 3,4,7,8-Me4Phen and from 2.2% to
4.9% in the case of 4,7-(MeO)2Phen), supporting the idea
that deprotonation is occurring to a larger extent with the
latter ligands.
The absolute order of maximum activity (highest TOF/h-1
in parentheses) was 4-methoxyphenanthroline (5710) >
4-carbomethoxy-7-methylphenanthroline(5409) >4-methyl-
phenanthroline (5326) > 3,4,7,8-Me4Phen (5010) > 4,7-
dimethylphenanthroline (4911) > 3-ethylphenanthroline
(4810) ≈ phenanthroline (4803) > 4,7-dimethoxyphenan-
throline (4754) > 3-tBuPhen (3969) . 2- methylphenan-
throline (571) . 2,9-Me2Phen (≈ 0).
From the results, with 4-methoxyphenanthroline being the
best ligand, followed by 4-carbomethoxy-7-methylphenan-
throline, it is evident that a next synthetic target may be the
nonsymmetric phenanthroline having a methoxy and a
carbomethoxy group. 3,4-Dimethylphenanthroline and its
derivatives in which the other pyridine ring is substituted
with an electron-withdrawing group are also promising
candidates.
Reactions under 100 bar of Carbon Monoxide. We have
previously shown that with phenanthroline as the ligand
the present catalytic reaction shows a first-order dependence
of the rate on the CO pressure at least in the range 40-
100 bar.7,8 Higher pressures had not been tested for technical
reasons, although they are expected to afford even higher
conversions. Since the hemilabile nature of the new ligands
may alter this trend, the best ligands and phenanthroline
were also tested under 100 bar of CO, to check if a positive
effect is still observed. Results are reported in Table S2
(Supporting Information), and the TOF values are graphi-
cally shown in Figure 4.
The positive effect of a higher pressure is maintained even
with the nonsymmetric phenanthrolines, indicating that CO
coordination to complexes of type 1 to give 2 (Scheme 1) has
been made easier by the use of the new ligands, but not
enough to shift the equilibrium between the two to the side of
the latter. Note that accelerating the aniline carbonylation
step to the point that it is no longer the rate-determining step
of the catalytic cycle is not desirable. Indeed, this would
result in the resting state of the catalyst being a palladium(0)
complex, and this in turn would lead to much faster catalyst
deactivation, as is indeed observed under some conditions
In any case, the anomalous shape of the 3,4,7,8-Me4Phen
curve results in an intersection with the phenanthroline one.
This observation explains some inconsistencies previously
reported in the literature, where 3,4,7,8-Me4Phen is a better
ligand than Phen according to some papers,8,29-32 while the
reverse holds in other cases.9 Clearly, the different concen-
trations and ligand/Pd ratios employed in different works
can justify these observations. That protonation may
become important in the case of the most basic ligands can
explain why 4,7-(MeO)2Phen is hardly effective under our
conditions, whereas it was shown to be a good ligand for the
(28) Wehman, P.; Borst, L.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
J. Mol. Catal. A: Chem. 1996, 112, 23–36.
(29) Alessio, E.; Mestroni, G. J. Mol. Catal. 1984, 26, 337–40.
(30) Alessio, E.; Mestroni, G. J. Organomet. Chem. 1985, 291, 117–
27.
(31) Bontempi, A.; Alessio, E.; Chanos, G.; Mestroni, G. J. Mol.
Catal. 1987, 42, 67–80.
(32) Cenini, S.; Ragaini, F.; Pizzotti, M.; Porta, F.; Mestroni, G.;
Alessio, E. J. Mol. Catal. 1991, 64, 179–190.

1470 Organometallics, Vol. 29, No. 6, 2010
Ferretti et al.
Phenanthrolines are being used as ligands in an increas-
ingly high number of catalytic reactions,36-43 and the use of
their nonsymmetric derivatives will surely prove beneficial in
at least some cases.
Experimental Section
General Procedures. Unless otherwise stated, all reactions and
manipulations were conducted under a dinitrogen atmosphere.
All solvents used in the catalytic reactions were dried by
standard procedures and distilled under dinitrogen immediately
before use. All glassware and magnetic stirring bars used in
catalytic reactions were kept in an oven at 120 °C for at least two
hours and allowed to cool under vacuum before use. 1,10-
Phenanthroline (Phen) and 2,9-dimethyl-1,10-phenanthroline
were purchased as hydrates. They were dried by dissolving them
in CH2Cl2, drying the resulting solution with Na2SO4, and
evaporating in vacuo the filtered solution. They were then stored
under dinitrogen. They can be weighed in the air without
problems, but must be stored in an inert atmosphere if water
uptake is to be avoided. The hydration degree of the commer-
cially available 4,7-dimethoxy-1,10-phenathroline (4,7-(MeO)2-
Phen), 3,4,7,8-tetramethylphenanthroline (3,4,7,8-Me4Phen),
and 4,7-dimethylphenanthroline was not obvious. Thus we
dried them all by the aforementioned procedure. Nitrobenzene
and aniline were distilled and stored under dinitrogen before
use. Triethylamine was distilled over CaH2 and kept under a
dinitrogen atmosphere. 1,3-Bis(diphenylphosphino)propane
(DPPP) was purified by dissolving it in refluxing hexane
(phosphine oxide impurities do not dissolve under these con-
ditions); the solution was hot filtered on a frit with a fine
porosity and stored under nitrogen at 5 °C to allow reprecipita-
tion. 4-MePhen, 2-MePhen, 8-methoxy-4-methylquinoline,
8-hydroxy-4-methylquinoline, 8-amino-4-methylquinoline,18
Figure 4. Nitrobenzene conversion for catalytic tests run under
100 bar of CO.
when the reaction is performed in the presence of a large
amount of aniline, affording diphenylurea as the final
product.10
The efficiency order of the tested phenanthrolines is the
same as observed under 60 bar, with 4-MeOPhen being the
best ligand. The corresponding TOF value (7900 h-1) is the
highest ever reported for the carbonylation of a nitroarene
with any catalytic system.33,34
Conclusions
The final goal of a mechanistic study on a catalytic
reaction should be the gaining of information that allows
improvement of the reaction efficiency without having to
rely on extensive trial and error. However, this goal is
seldom reached. In the present case, a previous mechanistic
study had suggested that nonsymmetric phenanthrolines, a
class of ligands for which basically no systematic studies
were present in the literature, should have given improved
performances. This turned out to be true for electronically
nonsymmetric ligands, whereas negative effects associated
with steric hindrance prevailed when present, and des-
pite the fact that the catalytic system had already been
extensively optimized, a significant improvement in rate
(57% with respect to the best value obtainable with phe-
nanthroline, measured under the same experimental con-
ditions) could be obtained. The use of nonsymmetric
phenanthrolines would have been far from obvious in the
absence of the mechanistic information because the only
published attempts to modify the same catalytic system by
the use of hemilabile ligands had afforded disappointing
results.35
31
Pd(dba)2,44 and [Pd(Phen)2][BF4]2 were prepared and char-
acterized according to the procedures reported in the literature.
All other chemicals were purchased from Aldrich, Acros, or
Alfa Aesar. NMR spectra were recorded on a Bruker AC300 FT
or on an Avance Bruker DPX300 spectrometer. Elemen-
tal analyses were recorded on a PerkinElmer 2400 CHN
elemental analyzer. All details on substituted phenanthroline
syntheses and characterization are reported in the Supporting
Information.
Catalytic Reactions. For a typical catalytic reaction, stock
solutions of the catalyst, PhNH2, and DMOP (2,2-dimethoxy-
propane) in nitrobenzene and of the ligand and H3PO4 (85% in
water) in methanol were prepared under dinitrogen, and the
reagent amounts measured by volume to avoid errors in weigh-
ing very small amounts of materials. Reagent amounts are
reported in the tables or in their footnotes, but in all cases the
catalyst concentration was 6.20 ꢀ 10-2 mM and [PhNO2] =
0.942 M (all reagent volumes are included in the concentration
calculation, as they are not negligible). The reactions were
conducted in parallel in three 10 mm wide ꢀ 40 mm high test
tubes, each having a magnetic stirring bar, which were located in
the holes of an aluminum block designed to fit a 200 mL stainless
steel autoclave. The block and the test tubes were placed inside a
(33) An apparently higher value, 11 548 h-1, has been reported for
the carbonylation of nitrobenzene and aniline to afford diphenylur-
ea.34 However, from an examination of the reported data it emerges
that this value was calculated by summing up the amounts of both
reacted nitrobenzene and aniline, which is not the standard way of
performing this type of calculations. Since the nitrobenzene and aniline
conversions were almost the same, the true TOF value is half than that
reported and lower than several of the values reported in the present
paper.
(34) Shi, F.; Zhang, Q.; Li, D.; Deng, Y. Chem.;Eur. J. 2005, 11,
5279–5288.
(35) Wehman, P.; vanDonge, H. M. A.; Hagos, A.; Kamer, P. C. J.;
van Leeuwen, P. W. N. M. J. Organomet. Chem. 1997, 535, 183–
193.
(36) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem. Res. 2009,
42, 1074–1086.
(37) Himeda, Y. Eur. J. Inorg. Chem. 2007, 3927–3941.
(38) Kwong, H.-L.; Yeung, H.-L.; Yeung, C.-T.; Lee, W.-S.; Lee, C.-
S.; Wong, W.-L. Coord. Chem. Rev. 2007, 251, 2188–2222.
(39) Arends, I. W. C. E.; ten Brink, G.-J.; Sheldon, R. A. J. Mol.
Catal. A: Chem. 2006, 251, 246–254.
(40) Chelucci, G.; Thummel, R. P. Chem. Rev. 2002, 102, 3129–3170.
(41) Widenhoefer, R. A. Acc. Chem. Res. 2002, 35, 905–913.
(42) Kito, M.; Urade, R. Met. Ions Biol. Syst. 2001, 38, 187–196.
(43) Thiel, W. R. Angew. Chem., Int. Ed. 1999, 38, 3157–3158.
(44) Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnet, J. J.; Ibers, J. A.
J. Organomet. Chem. 1974, 65, 253–66.

Article
Organometallics, Vol. 29, No. 6, 2010 1471
Schlenk tube with a wide mouth and the reagents added under
dinitrogen. Each tube was closed with a screw cap with a glass
wool-filled open mouth that allows gaseous reagents to ex-
change, and the block was rapidly transferred to the autoclave.
The autoclave was purged from air, charging CO at 60 bar and
discharging to 2 bar one time before performing the reaction.
CO was then charged at room temperature at the required
pressure, and the autoclave was immersed in an oil bath
preheated at 170 °C. Other experimental conditions are reported
in the captions to the tables. At the end of the reaction the
autoclave was quickly cooled with an ice bath and vented, and
the products were analyzed by gas chromatography (Dani 8620
gas chromatograph, equipped with a Supelco SLB-5 ms column;
naphthalene as an internal standard; CH2Cl2, 1 mL, was added
to the solution before taking a sample for the GC analysis to
dissolve naphthalene, which is hardly soluble in methanol).
Caution: the reaction is exothermic. We have routinely run the
same reactions here described on a larger (15-fold) scale in the
same autoclave employed here, but using a single 50 mL liner,
without problems. However, the exothermicity of the reaction
should be considered by those wishing to increase the nitroben-
zene or catalyst concentration.
Acknowledgment. We thank S. Raineri for performing
some preliminary experiments, Prof. A. Caselli for help
with NMR spectra, Prof. B. Milani (University of Trieste)
for helpful discussions, and the Italian MiUR (PRIN
2007HMTJWP_004) for financial support.
Supporting Information Available: Tables S1 and S2, report-
ing all catalytic reaction data; additional color figures showing
nitrobenzene conversion for catalytic tests using differently
substituted phenanthrolines as ligands; experimental details
for the synthesis of new phenanthrolines; mono- and bidimen-
sional 1H and 13C NMR spectra of the synthesized ligands. This
material is available free of charge via the Internet at http://
pubs.acs.org.