Phosphorus acids as highly efficient promoters for the palladium- phenanthroline catalyzed carbonylation of nitrobenzene to methyl phenylcarbamate

Article abstract of DOI:10.1002/adsc.200303143

A new family of promoters, based on phosphorus acids, is reported for the catalytic carbonylation of nitrobenzene to methyl phenylcarbamate by palladium-phenanthroline complexes. With the new promoters, unprecedented reaction rates (TOF up to 6000/h) and catalyst stability (TON up to 10 ⁵) could be reached. The best promoter is phosphoric acid, which is also very cheap, nontoxic and easily separable from the reaction products.

Full text of DOI:10.1002/adsc.200303143

FULL PAPERS
Phosphorus Acids as Highly Efficient Promoters for the
Palladium-Phenanthroline Catalyzed Carbonylation of
Nitrobenzene to Methyl Phenylcarbamate≤
Fabio Ragaini,* Michela Gasperini, Sergio Cenini
Dipartimento di Chimica Inorganica, Metallorganica e Analitica, ISTM CNR, and INSTM, UdR Milano, via Venezian
21, 20133 Milano, Italy
Fax: ( ‡ 39)-2-5031-4405, e-mail: fabio.ragaini@unimi.it
Received: September 9, 2003; Accepted: November 11, 2003
Abstract: A new family of promoters, based on could be reached. The best promoter is phosphoric
phosphorus acids, is reported for the catalytic carbon- acid, which is also very cheap, nontoxic and easily
ylation of nitrobenzene to methyl phenylcarbamate separable from the reaction products.
by palladium-phenanthroline complexes. With the
new promoters, unprecedented reaction rates (TOF Keywords: carbamates; carbonylation; homogeneous
up to 6000/h) and catalyst stability (TON up to 105) catalysis; nitroarenes; palladium
Introduction
ꢀ2†
The carbonylation of organic nitro compounds is a Despite an intense effort both in industrial and academ-
process with a high potential synthetic and industrial ic laboratories, no process has been developed up to now
interest, since many products can be obtained from nitro which may compete from an economical point of view
compounds and CO, including isocyanates, carbamates with the established technology employing phosgene.
and ureas.[1 3] Ureas and carbamates are important final This is mostly due to the insufficient turnover numbers
products and intermediates in the synthesis of pesticides (generally in the hundreds or even less) that even the
and fertilizers and mono- and diisocyanates are impor- most efficient catalysts can achieve, making catalyst
tant intermediates in the manufacture of pesticides, recycle too expensive. In recent years the catalytic
polyurethane foams plastics, synthetic leather, adhe- system based on palladium-phenanthroline complexes
sives, and coatings.
has emerged as the most active and promising for a
The classical method for the production of isocyanates possible industrial application.[4 31] Several groups have
requires the intermediate reduction of the nitro com- reported that the addition of acidic co-catalysts (car-
pound to amine, followed by reaction with phosgene. boxylic acids[11,12,15,18,31] or phenanthrolinium salts[20 22,24]
)
However, phosgene is a very toxic and corrosive markedly improves both rate and selectivity of the
material and an enormous effort has been applied to carbonylation of nitroarenes to give isocyanates or
the development of phosgene-free routes to isocyanates. carbamates. We were intrigued by van Leeuwen×s
Among these, the catalytic carbonylation of nitro observation[15] that no correlation was present between
compounds, particularly of aromatic ones, represents the acidity of the carboxylic acid employed as promoter
one of the most interesting alternatives, but the direct and the rate increase. This suggested to us that a
carbonylation of nitro compounds to the corresponding bifunctional activation process may be operative and we
isocyanates has proved to be a difficult reaction. decided as a working hypothesis to investigate the
However, in the presence of an alcohol, carbamates promoting activity of a series of substances that may
can be obtained more easily and with a high selectivity have a better bifunctional activation ability than car-
[Eq. (1)]:
boxylic acids. Although we must stress that at the
moment we only have some preliminary mechanistic
data indicating that a bifunctional activation is indeed
occurring, this working hypothesis proved fruitful and
allowed us to markedly improve the efficiency of the
ꢀ1†
If the isocyanate is the desired product, this can be catalytic system in terms of both reaction rate and
obtained by thermal cracking of the carbamate catalyst life. A preliminary communication of part of
[Eq. (2)]:
this work has been published.[32]
Adv. Synth. Catal. 2004, 346, 63 71
DOI: 10.1002/adsc.200303143
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
63

Fabio Ragiani et al.
FULL PAPERS
Table 1. Comparison of different promoters.[a]
ˆ
Catalyst
Promoter
Promoter/
Pd mol
ratio
T [8C]
PhNO2
conv.
PhNHCO2Me
sel. [%][c]
PhNH2
PhN(O) NPh
sel. [%][c]
sel. [%][c]
[%][b]
[Pd(Phen)2][BF4]2
[Pd(Phen)2][OTf]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][OTf]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][OTf]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][OTf]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
[Pd(Phen)2][BF4]2
135
135
135
135
135
135
135
135
135
135
135
135
150
150
150
170
170
170
20.7
13.0
19.9
16.5
39.3
22.4
23.8
14.5
21.8
18.0
25.8
31.7
45.1
45.3
83.7
87.0
96.7
98.0
90.5
79.2
98.4
86.0
96.9
88.2
81.1
85.4
81.7
92.0
74.0
80.8
89.7
95.4
91.2
90.4
90.0
92.4
1.1
0.5
1.4
1.1
PhCOOH
PhCOOH
25
25
25
25
25
25
25
7
Ph2P(O)OH
Ph2P(O)OH
2-HO,5-ClPy
2-HO,5-ClPy
2-HOPy
0.4
0.5
0.8
0.6
3.2
5.6
2.9
1.0
2.4
1.1
0.3
[PhenH][PF6][d]
[PhenH][PF6]
[PhenH][PF6]
25
16
2.8
2.0
2.9
1.7
0.5
5.7
2.6
0.8
PhCOOH
Ph2P(O)OH
25
25
PhCOOH
Ph2P(O)OH
25
25
2.2
[a]
Experimental conditions: Catalyst ˆ 2.0  10À2 mmol, mol ratios Pd/Phen/PhNO2 ˆ 1: 4: 730, PCO ˆ 60 bar, in methanol
(10 mL) for 1.5 h.
[b]
[c]
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC. Trace amounts (selectivity < 1%) of azobenzene were also detected.
Phen/cat. ˆ 3.
[d]
Results and Discussion
benzoic acid even on the reaction rate with
[Pd(Phen)2][BF4]2.
As candidates for bifunctional activation we initially 2) 2-Hydroxypyridine and its chlorinated analogue
investigated 2-hydroxypyridine,[33] previously shown by
us to be also a promoter for the reaction of Eq. (1) when
[Rh(CO)4]À is employed as catalyst,[34] its 5-chloro
show some promoting effect, but, at least for the
triflate catalyst, the effect is smaller than the one of
benzoic acid and they were not investigated further.
analogue and a phosphorus acid: diphenylphosphinic 3) Mestroni×s promoter [PhenH][PF6] is also effective
acid.[33,35] Van Leeuwen and co-workers have reported
on the promoting efficiency of carboxylic acids only in
with the tetrafluoroborate catalyst, in accord with
what is reported in the literature.[20 22,24] The reaction
was performed both at the molar ratio promoter/Pd
employed by Mestroni, 7:1, and at the one employed
by us, 25:1. Since by increasing the promoter/Pd
ratio even the total amount of phenanthroline is
increased, we also performed a reaction at an
intermediate ratio, 16:1, which indeed gave the
best results. Under these conditions [PhenH][PF6]
affords better conversions, but lower selectivities
with respect to benzoic acid.
conjunction with [Pd(Phen)2][TfO]2 (TfOÀ ˆ CF3SO3 ,
À
Phen ˆ 1,10-phenanthroline) as catalyst and at
1358C.[15,18] However, in another paper,[14] the same
authors reported that the related [Pd(Phen)2][BF4]2
complex affords better results. We have compared
both these complexes in the presence of the aforemen-
tioned promoters, also including benzoic acid and
[PhenH][PF6] for comparison and in a broader range
of temperatures. The results are reported in Table 1. The
main conclusions that can be drawn from the data 4) Diphenylphosphinic acid is clearly the best promot-
reported are the following:
er, and increases rate and selectivity with both
catalysts and at all temperatures.
1) We confirm that benzoic acid increases both con- 5) When the temperature is increased, the azoxyben-
version and selectivity when employed at 1358C with
[Pd(Phen)2][TfO]2 as catalyst. However, with the
more active tetrafluoroborate catalyst, no effect on
zene amount also increases, especially in the absence
of promoters.
conversion is observed at either 135 or 1508C, By working at 60 bar CO, the reaction temperature and
although an increase in selectivity is still observed. the amounts of phenanthroline and diphenylphosphin-
Only at 1708C we could observe a positive effect of ic acid were optimized. The catalytic ratio was in-
64
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Adv. Synth. Catal. 2004, 346, 63 71

Palladium-Phenanthroline Catalyzed Carbonylation of Nitrobenzene
FULL PAPERS
Table 2. Influence of the Phen/Pd ratio.[a]
ˆ
Phen /Pd mol ratio
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN(O) NPh
[b]
sel. [%][c]
sel. [%][c]
15
18
22
30
40
33.5
49.7
82.2
77.9
72.1
93.3
92.3
94.6
84.8
88.0
1.3
1.7
1.7
1.2
2.2
2.8
3.2
2.8
2.8
3.0
[a]
Experimental conditions: [Pd(Phen)2][BF4]2 ˆ 2.0  10À2 mmol, mol ratios Pd/Ph2P(O)OH/PhNO2 ˆ 1: 150: 2190, PCO
ˆ
60 bar, Tˆ 1708C, in methanol (30 mL), for 1 h.
[b]
[c]
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC. Trace amounts ( < 1%) of azobenzene were also detected in some cases.
Table 3. Influence of the reaction temperature and the Ph2P(O)OH/Pd ratio.[a]
ˆ
ˆ
Entry
T [ 8C]
Ph2P(O)OH/Pd
mol ratio
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN NPh
PhN(O) NPh
[b]
sel. [%][c]
sel. [%][c]
sel. [%][c]
1
2
3
4
5
6
7
8
9
170
180
190
200
170
180
190
170
170
170
170
25
25
25
25
75
75
75
100
150
225
300
55.7
83.6
85.6
80.1
68.2
84.9
80.8
78.7
82.2
79.8
78.5
85.8
76.9
65.1
57.8
91.0
88.5
81.7
93.6
94.6
94.8
90.6
2.0
1.4
1.2
1.2
1.4
1.8
1.6
1.4
1.7
1.7
1.7
6.2
13.6
23.1
26.6
3.0
4.3
12.0
3.3
1.6
3.1
3.2
0.8
1.9
0.6
0.6
2.8
2.5
3.6
10
11
[a]
Experimental conditions: [Pd(Phen)2][BF4]2 ˆ 2.0  10À2 mmol, mol ratios Pd/Phen/PhNO2 ˆ 1: 22: 2190, PCO ˆ 60 bar, Tˆ
1708C, in methanol (30 mL), for 1 h.
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC.
[b]
[c]
creased three-fold to avoid reaching complete con- chosen as a standard for the following optimization
version.
The results of the experiments performed with differ-
reactions.
The effect of temperatures higher than 1708C was
ent Phen/Pd ratios are reported in Table 2. The effect is then examined (Table 3, entries 1 7). The reactions
very marked. By increasing the Phen/Pd ratio from 15 to were investigated both at mol ratios Ph2P(O)OH/Pd ˆ
22, the nitrobenzene conversion increases from 33 to 25 and 75. The first is the same as the one used for the
82%. Higher ratios cause a decrease in the conversion, experiments in Table 1, but corresponds to a lower acid
but the effect is smaller. Such an effect has already been concentration in solution, since the volume was in-
observed by us for a related catalytic system for the creased from 10 to 30 mL. The second ratio keeps the
synthesis of isocyanates[11] and is probably due to a series acid concentration equal to the one of the first series of
of complexation equilibria [Eq. (3)], where only the experiments, although the acid/Pd ratio is changed.
complex with one phenanthroline is catalytically active.
The results show that the selectivity is always highest
at 1708C, although the conversion is higher at 180 and
1908C. At temperatures higher than 1708C, formation
of some metallic palladium was observed at the end of
the reaction. The increase in reaction temperature also
causes a steady increase in the amount of azoxybenzene
ꢀ3†
The selectivity is also highest at the 22:1 ratio and the formed, confirming the trend previously observed,
corresponding phenanthroline concentration has been which is only partly moderated by an increase in the
Adv. Synth. Catal. 2004, 346, 63 71
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Fabio Ragiani et al.
FULL PAPERS
Figure 1. Influence of the Ph2P(O)OH/Pd mol ratio on the
PhNO2 conversion. Data in Table 3, entries 1, 5, 8 11. The
curve was manually drawn and does not correspond to any
mathematical fitting.
Figure 2. Dependence of PhNO2 conversion on reaction time.
Data in Table 5, entries 4 7. The linear regression affords a
line with equation: Conv. %ˆ 23.49 t 18.56 (R2 ˆ 0.999).
acid amount. A higher acid amount accelerates the reaction to be only 1.3 times slower in the first hour
reaction at 1708C, but not at the higher temperatures, than in the following ones.
likely because the catalytic system decomposes.
Since aniline is known to be intermediately formed in
Keeping the temperature and the phenanthroline several catalytic carbonylation reactions of nitroar-
amount constant, the Ph2P(O)OH amount was then enes,[1 3,19] we investigated the effect of its addition since
optimized (Table 3, entries 1, 5, 8 11, Figure 1). The the beginning. As shown in Table 5, the addition of
reaction rate increases up to a mol ratio Ph2P(O)OH/ aniline in a 4% molar amount with respect to the starting
Pd ˆ 150, then it decreases a little. The selectivity is nitrobenzene accelerates the reaction in the first hour by
almost indistinguishable between the ratios 100 and 225, a factor of about 4. Thus it is clear that the induction time
but it is lower outside this range.
is for the most part due to the required generation of
By halving the amount of palladium and doubling the aniline, which is slow in the dry solvent employed. The
reaction time (Table 4), the conversion decreased from addition of an equimolar amount of aniline with respect
82 to 62%, but by further reducing the amount of to nitrobenzene has been previously reported to accel-
palladium to ca. 1/5 of the initial one and increasing the erate the rate of the reaction with a palladium-phenan-
reaction time five times (five hours, molar ratio nitro- throline catalyst,[16] but in the presence of such an high
benzene/Pd ˆ 10000, or catalyst ˆ 10À2 mol %) the con- amount of aniline the selectivity of the reaction much
version even increased to 97.8%. The selectivity low- decreased and large amounts of azoxybenzene were
ered from 94.6 to 73.5 along the series, but it raised back formed.
to 87.4 when 1 mL of 2,2-dimethoxypropane was added
At this stage other phosphorus acids were tested. A
to the reaction mixture, the conversion remaining comparison of the data in Table 6 shows that the
virtually unchanged (Table 4, entries 3, 4). Dimethoxy- introduction of an electron-donating group on the
propane acts as an internal drying agent and its addition phenyl rings of diphenylphosphinic acid has a small
has already been shown to be beneficial for this positive effect, but the electron-withdrawing chloride is
reaction.[20 24] This shows that the reaction is complex not tolerated. Phenylphosphonic acid and its substituted
but the system does not deactivate on prolonged work- analogues are a better class of promoters, but phenyl-
ing. On the contrary, decreasing five-fold the palladium phosphinic acid, which has a hydrogen atom directly
concentration increases the turnover frequency. Under linked to the phosphorus atom and can act as a reductant
these conditions (Table 4, entries 4 7), the reaction towards palladium, completely deactivated the catalytic
shows an induction time of about one hour, after which it system, apparently because of fast formation of inactive
proceeds with a zero order in PhNO2 without showing palladium metal. Even the more acidic dithiodiphenyl-
any rate decrease due to possible decomposition of the phosphinic acid was not a suitable promoter. Worthy of
catalytic system (Figure 2). The reaction is 5.4 times note, this acid is known not to be a good bifunctional
slower during the first hour than in any of the following catalyst.[33] Very interestingly, the best conversion was
ones. It should be noted that the autoclave takes about obtained with commercial 85% phosphoric acid ! This is
15 min to reach the final temperature when immersed in an ideal promoter in terms of cost, absence of toxicity
the preheated oil bath (see Experimental Section), but and ease of separation from the reaction products. The
the reaction does surely start well before full equilibra- 1:1 mixture of mono- and dimethyl phosphate, obtained
tion has been achieved. Even a full 15 min delay time in by reaction of P4O10 with the stoichiometric amount of
the first hour, however, would by itself cause the methanol, was less efficient, but still retained a high
66
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Palladium-Phenanthroline Catalyzed Carbonylation of Nitrobenzene
FULL PAPERS
Table 4. Influence of high catalytic ratios and reaction time.[a]
ˆ
ˆ
Entry
cat.
[mmol]
t
PhNO2/Pd
mol ratio
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN NPh
PhN(O) NPh
TOF
[b]
[h]
sel. [%][c]
sel. [%][c]
sel. [%][c]
[hÀ1]
1
2
3
2.0 Â 10À2
1.0 Â 10À2
4.4 Â 10À3
4.4 Â 10À3
4.4 Â 10À3
4.4 Â 10À3
4.4 Â 10À3
1
2
5
5
1
2
3.5
2190
4380
82.2
62.0
97.8
97.7
4.4
94.6
90.2
73.5
87.4
82.2
90.6
94.7
1.7
1.8
3.1
2.0
17.8
7.9
0.6
traces
3.8
0.5
2.8
4.9
7.5
1.1
1800
1359
1959
1956
442
10000
10000
10000
10000
10000
4[d]
5[d]
6[d]
7[d]
28.1
65.7
1.4
1.4
1404
1878
2.7
[a]
Experimental conditions: Catalyst ˆ [Pd(Phen)2][BF4]2, Phen ˆ 0.44 mmol, Ph2P(O)OH ˆ 3.00 mmol, PCO ˆ 60 bar, Tˆ
1708C, in methanol (30 mL).
[b]
[c]
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC.
[d]
2,2-Dimethoxypropane (1 mL) was also added.
Table 5. Influence of the addition of aniline.[a]
ˆ
t [h]
PhNH2/Pd
mol ratio
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN(O) NPh
[b]
sel. [%][c, d]
sel. [%][c]
1
1
1.5
1
14.9
43.2
86.0
59.6
93.8
95.1
93.8
96.9
6.2
1.8
2.0
0.8
100
100
200
0.8
0.6
0.8
[a]
Experimental conditions: [Pd(Phen)2][BF4]2 ˆ 2.8 mg, 4.4  10À3 mmol, mol ratios Pd/Phen/Ph2P(O)OH/PhNO2 ˆ
1: 100: 682: 5000, PCO ˆ 60 bar, Tˆ 1708C, in methanol (30 mL) ‡ 2,2-dimethoxypropane (1 mL).
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC. Azobenzene was below the detection limit (0.1%).
Calculated considering only the aniline amount in excess with respect to the initially charged one.
[b]
[c]
[d]
promoting efficiency, showing that a partial esterifica- reactions under the reaction conditions, some of which
tion of the acid does not block catalytic activity. Such regenerate water. We have previously discussed some of
esterification does indeed occur during the reaction, but these problems in the palladium-catalyzed carbonyla-
to a small extent. Under the conditions of Table 3 but for tion reactions of nitroarenes[1,19] and detailed the com-
a longer time (6 h), 32% of the added phenylphosphonic plex situation present when the same reaction is
acid was transformed into the monomethyl ester and no catalyzed by Ru3(CO)12/[Et4N][Cl].[36] Preliminary
diester was detectable by 31P NMR. The esterification is mechanistic studies on the present catalytic system
a purely organic transformation and essentially the same indicate that at least three different mechanisms are
amount of monoester (30%) is obtained under the same operating at the same time. Discussing them now is
conditions, but in the absence of the metal and nitro- premature, but the results reported here indicate any-
benzene.
way that further room exists for optimization of the
The fact that 85% H3PO4 gave a better conversion experimental conditions. Concerning the action of
than the pure acid is at first sight surprising, since in the dimethoxypropane, it is worth noting that in this work
first case some water is also added. The results show that we could not detect the formation of acetone, the
the addition of this water is beneficial, despite the fact product of its reaction with water, because this last
that the addition of a drying agent is also positive. The compound is too volatile to be separated from the much
apparent inconsistency can be at least qualitatively larger amount of methanol, employed as solvent.
explained by considering the complex role of aniline in However, in a related work[31] we could indirectly
the catalytic system. Depending on the reaction mech- evidence its formation by observing small amounts of
anism, aniline can be, and often is, an intermediate in the isopropylidene-phenylimine, the Schiff base derived
carbonylation reaction of nitrobenzene, but it is also a from the condensation of acetone with aniline, among
by-product. It can be produced by reaction of nitro- the products.
benzene, CO, and water and is also involved in several
Adv. Synth. Catal. 2004, 346, 63 71
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Fabio Ragiani et al.
FULL PAPERS
Table 6. Comparison of different phosphorus promoters.[a]
ˆ
Promoter
Promoter/Pd
mol ratio
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN(O) NPh
[b]
sel. [%][c]
sel. [%][c]
[d]
[d]
[d]
[d]
4.6
37.0
37.8
7.7
42.5
49.2
34.6
13.7 (11.0)[d]
89.5 (87.9)[d]
93.3 (91.7)[d]
64.0 (60.3)[d]
86.8
51.0
1.8
1.9
Ph2P(O)OH
682
682
682
682
682
682
682
682
682
753
682
682
682
227
682
682
(4-MeC6H4)2P(O)OH
(4-ClC6H4)2P(O)OH
PhP(O)(OH)2
4-MeC6H4P(O)(OH)2
4-ClC6H4P(O)(OH)2
Ph2P(S)SH
PhPH(O)OH
H3PO4 100%
H3PO4 100%
H3PO4 85%
<0.1
0.4
0.7
1.6
1.6
2.1
90.3
86.4
42.6
47.9
55.1
33.4
17.1
10.6
64.0
63.0
93.5
89.0
87.1
2.8
0.9
3.0
1.7
<1
18.6
[d]
OP(OMe)(OH)2/ OP(OMe)2(OH) 1: 1
PhCOOH
85.4 (84.0)[d]
83.6 (77.3)[d]
83.8 (81.3)[d]
84.4
[d]
[d]
[PhenH][PF6]
H3PO4 85%[e]
5.5
4.4
3.0
2.4
H3PO4 85%[f]
84.9
[a]
Experimental conditions: [Pd(Phen)2][BF4]2 ˆ 1.4 mg, 2.2  10À3 mmol, mol ratios Pd/Phen/PhNH2/PhNO2 ˆ
1: 100: 200: 7500, PCO ˆ 60 bar, in methanol (15 mL) ‡ 2,2-dimethoxypropane (0.5 mL) for 1 h.
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Aniline selectivity is calculated considering only the aniline amount in
excess with respect to the initially charged one. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC. Azobenzene was below or very close to the detection limit (0.1%).
Less aniline was found at the end of the reaction with respect to the initially charged one. The value in parentheses refers to
the selectivity with respect to the sum of PhNO2 and PhNH2 reacted.
[b]
[c]
[d]
[e]
[f]
3,4,7,8-Tetramethyl-1,10-phenanthroline (TMPhen) was employed in place of Phen: mol ratio TMPhen/Pd ˆ 100.
3,4,7,8-Tetramethyl-1,10-phenanthroline (TMPhen) was employed in place of Phen: mol ratio TMPhen/Pd ˆ 67.
Benzoic acid and [PhenH][PF6] were also tested under The reaction is clearly first order in CO pressure
the optimized conditions (Table 6) and gave results (Table 7, Figure 3). Because of technical limits, we could
markedly inferior to all phosphorus acids, with the not investigate initial pressures higher than 100 bar, but
obvious exceptions of phenylphosphinic and dithiodi- they should clearly afford even better results. It should
phenylphosphinic acids, although the TONs observed be noted that the best result corresponds to a turnover
are anyway higher than those previously reported for frequency (TOF) of almost 6000/h. The highest value
these same promoters.
previously reported in the open literature for the
Mestroni and we have previously noted that 3,4,7,8- carbonylation reaction of nitrobenzene to afford methyl
tetramethyl-1,10-phenanthroline (TMPhen) generally phenylcarbamate is 960/h.[23] The catalytic system is very
affords better conversions and sometimes even better stable and by decreasing the palladium amount we could
selectivities than unsubstituted Phen in carbonylation obtain an unprecedented TON of 105 in 24 h, albeit with
reactions of nitrobenzene catalyzed by palladium com- a somewhat lower selectivity (77.5%),[37] reaching the
plexes.[7 9,11] Under our conditions (Table 6) and with limit for which a commercial application can be
85% H3PO4 as the acid, TMPhen increased the con- considered.
version from 55.1 to 64.0%, but the selectivity in
An analysis of the data in Tables 1, 3, and 6 indicates
carbamate decreased slightly (from 87.1 to 84.4%). that the beneficial effect of all promoters on the
Since TMPhen is a stronger ligand than Phen and the selectivity is due to the decrease in the amount of azo-
ideal TMPhen/Pd ratio is usually lower than the ideal and azoxybenzene formed. These last by-products are
Phen/Pd ratio,[11] we also repeated the reaction at a formed more easily at higher temperatures and are only
lower TMPhen/Pd ratio (67 instead of 100), but the very slowly converted to carbonylated products. The
results are indistinguishable within the limits of the effect of the promoter may be that of (a) avoiding their
experimental error. Since TMPhen is much more formation or (b) accelerating their conversion to
expensive than Phen, it is questionable if the small carbamate.[38] When azoxybenzene was used as a
rate increase observed may justify its use ona large scale. substrate in place of nitrobenzene (under the conditions
The influence of the CO pressure was finally inves- of Table 1, but at a molar ratio azoxybenzene/Pd ˆ 365)
tigated employing 85% phosphoric acid as promoter. in the absence of promoters, only a 4.9% conversion was
68
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Adv. Synth. Catal. 2004, 346, 63 71

Palladium-Phenanthroline Catalyzed Carbonylation of Nitrobenzene
FULL PAPERS
Table 7. Influence of CO pressure.[a]
ˆ
ˆ
PCO [bar]
PhNO2
conv. [%]
PhNHCO2Me
sel. [%][c]
PhNH2
PhN NPh
PhN(O) NPh
[b]
sel. [%][c]
sel. [%][c]
sel. [%][c]
40
60
80
100
37.0
55.1
65.1
81.2
82.4
87.1
87.9
87.5
2.8
3.0
4.0
3.0
3.0
1.7
1.0
0.8
traces
[a]
Experimental conditions: [Pd(Phen)2][BF4]2 ˆ 1.4 mg, 2.2  10À3 mmol, mol ratios Pd/Phen/PhNH2/85% H3PO4/PhNO2 ˆ
1: 100: 200: 682: 7500, in methanol (15 mL) ‡ 2,2-dimethoxypropane (0.5 mL) for 1 h.
Calculated with respect to the starting PhNO2.
Calculated with respect to the converted PhNO2. Aniline selectivity is calculated considering only the aniline amount in
excess with respect to the initially charged one. Most of the remaining mass balance is due to diphenylurea, which was
observed, but not quantified by GC.
[b]
[c]
Experimental Section
General Procedure
All solvents were dried by standard procedures, distilled and
stored under dinitrogen before use. [Pd(Phen)2][BF4]2,[7]
[Pd(Phen)2][OTf]2,[14] [PhenH][PF6],[39] and Ph2P(S)SH[40]
were prepared as reported in the literature. (4-MeC6H4)2-
[41] and (4-ClC6H4)2P(O)OH[42] were synthesized by the method
of Kosalapoff and Struck,[43] but employing H2O2 as the oxidant
in place of Br2, as also reported in ref.[42], and characterized by
comparison of their analytical data with the published
ones.[41,42] 4-MeC6H4P(O)(OH)2 and 4-ClC6H4P(O)(OH)2
were synthesized by reaction of triethyl phosphite with 4-
MeC6H4Br and 4-ClC6H4Br, respectively, in the presence of
NiBr2, following the method of Tavs,[44] followed by hydrolysis
of the ester with 37% HCl as in ref.[45] They were characterized
by comparison of their analytical data with those reported in
the literature.[46] Nitrobenzene was purified by shaking with
10% H2SO4, washing with water, and drying with Na2SO4,
followed by distillation under dinitrogen and storage under an
Figure 3. Influence of CO pressure on PhNO2 conversion.
Data in Table 7. The linear regression affords a line with
equation: Conv. %ˆ 0.713 PCO ‡ 9.69 (R2 ˆ 0.989).
observed. The only observable product was azobenzene,
58.5%. When Ph2P(O)OH was added [Ph2P(O)OH/ inert atmosphere. Aniline was distilled and stored under
dinitrogen before use. All other reagents were commercial
products and were employed as received.
Pd ˆ 25], the conversion increased to 9.5% and azoben-
zene remained the dominant product (67.4%). This
increase in reactivity is much too low to account for the
increase in selectivity observed in the catalytic reaction,
especially on considering that azobenzene is clearly
converted at an even slower rate than azoxybenzene, but
is always present in a much lower amount. Thus it is clear
that the promoter depresses the formation of azoxy-
benzene and not simply accelerates its conversion.
Catalytic Reactions
In a typical catalytic reaction, the catalyst, Phen, PhNO2, and,
when required, PhNH2 and the acidic promoter were weighed
in a glass liner. In the cases in which less than 2 mg catalyst had
to be weighed, a solution of the catalyst in nitrobenzene was
prepared instead, and a known volume of the solution was
added, in order to avoid large errors in weighing very small
amounts of catalyst. The liner was placed inside a Schlenk tube
with a wide mouth under dinitrogen and was frozen at À 788C
with dry ice, evacuated and filled with dinitrogen, after which
the solvent was added. After the solvent was also frozen, the
liner was closed with a screw cap having a glass wool-filled
open mouth which allows gaseous reagents to exchange and
rapidly transferred to a 200-mL stainless steel autoclave with
magnetic stirring. The autoclave was then evacuated and filled
with dinitrogen three times. CO was then charged at room
temperature at the required pressure and the autoclave was
immersed in an oil bath preheated at the required temperature;
Conclusion
In conclusion we have found an improved catalytic
system for the carbonylation of nitrobenzene that, for
the first time, yields activities and catalyst life in the
range necessary for industrial applications. Preliminary
results indicate that the improved features also apply to
the economically very important dinitrotoluenes. Opti-
mization of the experimental conditions with these
substrates is in progress.
Adv. Synth. Catal. 2004, 346, 63 71
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69

Fabio Ragiani et al.
FULL PAPERS
the autoclave took about 15 min to fully equilibrate at the final
temperature. Other experimental conditions are reported in
the captions to the tables and figures. At the end of the reaction
the autoclave was cooled with an ice bath, vented and the
products were analyzed by gas chromatography (Dani 8620 gas
chromatograph, equipped with a PS 255 column; naphthalene
as an internal standard).
[17] P. Wehman, H. M. A Donge, A. Hagos, P. C. J. Kamer,
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Acknowledgements
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We thank Enichem for financial support and The Dow
Chemical Company for the permission to publish these results.
We also thank Dr. C. Querci (Polimeri Europa, Istituto
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1
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Adv. Synth. Catal. 2004, 346, 63 71

Palladium-Phenanthroline Catalyzed Carbonylation of Nitrobenzene
FULL PAPERS
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71