Solvent-free and safe process for the quantitative production of phosgene from triphosgene by deactivated imino-based catalysts

Article abstract of DOI:10.1021/op100239n

Phosgene is quantitatively formed from solid triphosgene in a solvent-free and safe process without any reaction heat, catalyzed by planar N-heterocycles with deactivated imino functions. The rate of phosgene generation is adjustable to the rate of phosgene consumption in the subsequent phosgenation reaction by thermal control, catalyst concentration, and in some cases, specific properties of selected metal phthalocyanines. A thermal runaway reaction of this process is impossible.

Full text of DOI:10.1021/op100239n

Organic Process Research & Development 2010, 14, 1501–1505
Solvent-Free and Safe Process for the Quantitative Production of Phosgene from
Triphosgene by Deactivated Imino-Based Catalysts
Heiner Eckert* and Johann Auerweck
Department of Chemistry, Technische UniVersitaet Muenchen, Lichtenbergstr. 4, Garching 85747, Germany
Scheme 1. Decomposition of triphosgene (1a) into carbon
tetrachloride, carbon dioxide, and 1 equiv of phosgene (3)
Abstract:
Phosgene is quantitatively formed from solid triphosgene in a
solvent-free and safe process without any reaction heat, catalyzed
by planar N-heterocycles with deactivated imino functions. The
rate of phosgene generation is adjustable to the rate of phosgene
consumption in the subsequent phosgenation reaction by thermal
control, catalyst concentration, and in some cases, specific proper-
ties of selected metal phthalocyanines. A thermal runaway reaction
of this process is impossible.
phosgene in most reactions, yet several phosgenation reactions
are advantageously carried out with phosgene, that is, when
excessive triphosgene is difficult to remove during the reaction
workup because of its high boiling point of over 200 °C. Its
excess can be destroyed by hydrolysis, when phosgenation
products are not sensitive to moisture as are carbonates,
carbamates, ureas, diarylketones, alkylhalides, cyanides, and
isocyanides. However, for chloroformates, acyl chlorides,
anhydrides, isocyanates, and carbodiimides, which are very
sensitive to hydrolysis, workup after phosgenation reactions by
use of water has to be carried out skilfully and is limited to
rather small quantities. Phosgene, however, can easily be
removed in the workup by evaporation.
In production lines, the use of gaseous phosgene is advanta-
geous as a result of its easy charging as well as the facile and
quantitative removal of excess. To benefit from the chemical
and ecological advantages (fast decomposition by air humidity
and less harmful decomposition products in contrast to other
substitutes such as thionyl chloride or phosphoryl chloride) of
phosgene despite its high toxicity, the concept of the Safety
Phosgenation has been designed.1e,5 Core to it is the phosgene
production “on demand of consumer” without any storage. To
avoid both gases chlorine and carbon monoxide for the
production of phosgene, solid triphosgene is the safest precursor
for production, transport, and storage of phosgene.
Triphosgene completely decomposes by contact with metal
salts, Lewis acids, active surfaces such as silica gel, by “dirt”,
or at temperatures above 200 °C in a spontaneous, uncontrolled,
and exothermic reaction into carbon dioxide, carbon tetrachlo-
ride, and 1 equiv of phosgene (Scheme 1).1b,4c The reaction
mechanism is an electrocyclic reaction of the conformer 1a of
triphosgene (which is interchangeable with 1 by free rotation
of both trichloromethyoxy groups at rt) through a six-membered
transition state 1b, which causes the simultaneous formation
of the three products carbon tetrachloride, carbon dioxide, and
phosgene in a molecular ratio of 1:1:1,1b,4c measured by a
thermogravimetric analyzer interfaced to a Fourier transform
Introduction
Phosgene (3) is a highly useful and versatile chemical in
performing syntheses.1a Although consisting of only four atoms,
four important transformations can be carried out with it in
organic chemistry: chloro-carbonylation, carbonylation, chlo-
rination, and dehydration, by which chloroformates, carbonates,
carbamates, ureas, isocyanates, acyl- and arylchlorides, anhy-
drides, cyanides, isocyanides, and carbodiimides can be gener-
ated, as well as the corresponding heterocycles.1a-3 Phosgene
reacts in a distinct way with high yields and pure products, but
it is a strong and malicious toxic gas (bp 8 °C). Great efforts
have been made to displace phosgene by numerous substitutes
(a comprehensive review on this is given in ref 1c), and its
most versatile equivalent is triphosgene (1),4,1 which was
introduced in 1987,4a because of its high stability as a solid
(mp 80 °C) and its low vapor pressure (2 × 10-4 bar at 20
°C).1d Triphosgene has proved to be a valuable substitute for
* Corresponding author. E-mail: eckert@tum.de.
(1) (a) Cotarca, L.; Eckert, H. Phosgenations-A Handbook; Wiley-VCH:
Weinheim, 2003. (b) Cotarca, L.; Eckert, H. Phosgenations-A
Handbook; Wiley-VCH: Weinheim, 2003; pp 20-21. (c) Cotarca, L.;
Eckert, H. Phosgenations-A Handbook; Wiley-VCH: Weinheim,
2003; pp 44-520. (d) Cotarca, L.; Eckert, H. Phosgenations-A
Handbook; Wiley-VCH: Weinheim, 2003; p 41. (e) Cotarca, L.; Eckert,
H. Phosgenations-A Handbook; Wiley-VCH: Weinheim, 2003; pp
14-16, 613-615.
(2) Recent online information: www.ch.tum.de/oc1/HEckert/research.
htm.
(3) (a) Senet, J. P. The Recent AdVance in Phosgene Chemistry; SNPE:
Paris, 1997; Vol. 1. (b) Pasquato, L.; Modena, G.; Cotarca, L.; Delogu,
P.; Mantovani, S. J. Org. Chem. 2000, 65, 8224–8228. (c) Senet, J. P.
Sci. Synth. 2005, 18, 321–377. (d) Dunlap, K. L. In Kirk-Othmer
Encyclopedia of Chemical Technology, 5 ed.; Wiley: New York, 2006;
Vol. 18, pp 802-814. (e) Nielsen, D. H.; Burke, T. G.; Woltz, P. J. H.;
Jones, E. A. J. Chem. Phys. 1952, 20, 596–604. (f) Gordon, E. P.;
Enakaeva, V. G.; Korotchenko, A. V.; Mitrokhin, A. M. Russian Patent
RU 2299852, 2007.
(4) (a) Eckert, H.; Forster, B. Angew. Chem. 1987, 99, 922–923; Angew.
Chem., Int. Ed., 1987, 26, 894–895. (b) Eckert, H. TUM-Mitteilungen
(Technische UniVersitaet Muenchen) 2006, 3, 68–69. (c) Cotarca, L.;
Delogu, P.; Nardelli, A.; Sunjic, V. Synthesis 1996, 553–576. (d)
Triphosgene; Ubichem: U.K., 1999; CD-ROM. (e) Su, W.; Zhong,
W.; Bian, G.; Shi, X.; Zhang, J. Org. Prep. Proced. Int. 2004, 36,
499–547.
(5) (a) Eckert, H.; Drefs, N. Chemanager 2006, (3), 10. (b) http://
www.buss-ct.com/e/reaction_technology/Phosgene_Generation.
php?navid)41.
10.1021/op100239n  2010 American Chemical Society
Published on Web 10/26/2010
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Scheme 2. Controlled transformation of triphosgene (1)
according to Scheme 2 runs in a heterogeneous reaction. All
catalysts 4a-4h fulfill the above criteria and are stable and
recyclable. Outstandingly stable over many catalytic cycles are
4d-4h with a metal phthalocyanine (MPc)8a,b structure (belong-
ing to the most stable organic compounds of all); their activity
can be tuned by the properties of the central metals in 4d-4h
and the crystal modifications of the complexes, as for 4d versus
4e. So the R-CuPc (4d) is 90 times more reactive than its ꢀ-form
(4e), as calculated with the reaction data from Table 1, entries
7 and 9. Even after intensive use of 4d over 10 years with a
hundred batches of phosgene production, no decline in the
catalytic efficiency of 4d has been observed, which corresponds
to a TON (turnover number) of 5 × 104 (entry 8). Reaction
rates can be conveniently adjusted by either catalyst concentra-
tion (0.02-2 mol %)7 or temperature control (80-115 °C) and
can easily reach a TOF (turnover frequency) of 1.2 × 103 h-1
(entry 6). This is an appropriate TOF value for managing the
kinetics to adjust the rate of phosgene generation to the rate of
phosgene consumption of the subsequent phosgenation reaction
in an optimal way. Reaction times in the range of some minutes
up to 1 h can preferably be achieved with 4a-4f as catalysts.
For reaction times over many hours 4g and 4h are the
appropriate catalysts. In all reactions of triphosgene with 4a-4h
the resulting phosgene is of high purity, >99%. Mere pyridine
served as a reference substance, but it effects instantaneous
decomposition of triphosgene and is not at all appropriate to
produce phosgene in a solvent-free way (entry 13, Table 1).
Uncatalyzed reaction of triphosgene under the conditions of
Table 1 is not observed (entry 1, Table 1).
Reaction in Scheme 2 is controlled by temperature. Using
4h (Table 2) an increase of 25 °C in reaction temperature from
90 to 115 °C effects an acceleration of the volume flow of
phosgene and thus of the reaction rate by a factor of 7. The
reaction of Scheme 2 yields a further effect on safety: by turning
off the heater, transformation of triphosgene comes to a halt
and liquid triphosgene crystallizes, whereby its vapor pressure
plunges down. The reaction can simply be continued by heating
again.
This thermochemical performance is proven by differential
scan calorimeter (DSC) measurements of the process. The
conversion enthalpy of triphosgene into phosgene (Scheme 2,
catalyst R-CuPc) is ∆Hconversion ) +9 J g-1 at 81 °C; the reaction
is slightly endothermic. The scan ran up to 250 °C with 10
°C/min, and this fast acceleration of temperature did not provide
the behavior of a run away (Figure 1). The enthalpy of the
thermal decomposition of triphosgene (Scheme 1) is ∆Hdecomp
) -217 to -243 J g-1, starting at 213 °C; this reaction is
moderately exothermic. Since the range (80-115 °C) of the
slightly endothermic conversion reaction (Scheme 2) is more
than 100 °C below the moderate exothermic decomposition
reaction (Scheme 1), a thermal runaway is impossible. Beyond
this, the process guarantees an emergency stop by simply cutting
off heat.
into 3 equiv of phosgene (3) catalyzed by 4
infrared spectrometer (TGA-FTIR). For the thermal decomposi-
tion of triphosgene, decomposition enthalpies of ∆Hdec ) -200
to -278 J g-1 have been published.4c,d
Until now phosgene has been prepared from triphosgene in
a practical way only in solution in an uncontrolled reaction by
use of tertiary amines, pyridine in dichloromethane or tetrahy-
drofuran, or catalysis by Aliquat 336 in hexane.3b Also inert
high temperature solvents have been used to achieve phosgene
from triphosgene without diphosgene impurities.3f
Results and Discussion
By means of a specific catalyst 4, however, liquid triphos-
gene (1, mp 80 °C) can be transformed solvent-free and
quantitatively under heating with an oil-bath or an IR-heater in
a controlled and adjustable process into 3 equiv of phosgene
(Scheme 2).6 Diphosgene is formed as an intermediate, which
immediately reacts to form phosgene. Highly specific catalysts
are those who effect (i) an electronic push of the weak
nucleophilic imino-group of 4 to the carbonyl group of
triphosgene (1), (ii) the leaving of a trichloromethoxy group,
(iii) the generation of a carbonyl group from the latter by
migrating a chloride to the remaining trichloromethoxycarbonyl
group and thus forming one phosgene (3) and diphosgene (2),
(iv) the leaving of the second trichloromethoxy group, and (v)
the generation of a carbonyl group by migrating a chloride to
the remaining acyl chloride group and thus forming two
molecules of phosgene (3). Simultaneously the size and planar
structure of 4 prevents as a barrier between both trichloromethyl
groups in 1 the formation of the six-membered transition state
1b and thus makes the reaction of Scheme 1 impossible.
All of this will be realized by designing both the electronic
and steric properties of catalysts 4a-4h (Scheme 2 and Table
1).6 Because these are insoluble in molten triphosgene, catalysis
Phosgenation Reactions
The controlled production of phosgene from triphosgene can
be performed with an external phosgene generator with a
(6) Eckert, H.; Dirsch, N.; Gruber, B. (former Dr. Eckert GmbH, now
Buss Chem Tech AG) German Offen. DE 19740577, 1999 (Sep. 15,
1997), Chem. Abstr. 1999, 130, 211406.; WO 9914159, 1999; Eur.
Pat. EP 1017623, 2002; U.S. Patent US 6399822, 2002; Japanese
Patent JP 2001516692, 2001.
(7) Mole percent 4 referring to 3 phosgene equivalents of 1.
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Table 1. Catalysts (4) and reaction data of Scheme 2 with conversions of 10-5,000 g of triphosgene (1) into phosgene (3)
bath
temp [°C]
reaction
temp [°C]
reaction
time [min]
TOF
[h-1
yield of
3 [wt %]
entry
4
catalyst
mol % of 47
TON
]
1
None
115
115
100
100
100
100
100
100
115
100
115
115
85
a
0
2
4a
4b
4b
4c
4d
4d
4d
4e
4f
phenanthridine
poly(2-vinyl-pyridine)
poly(2-vinyl-pyridine)
H2Pc
0.1
1
0.1
1
1
95
90
21
103
2.9 × 103
1.2 × 103
103
98
3
5
102
96
4
90
60
103
98
5
90
4
5
102
1.5 × 103
1.2 × 103
8.6 × 102
8.6 × 102
30
97
6
R-CuPcb
90
102
96
7
R-CuPc
0.2
0.2
2
90
35
5 × 102
5 × 104
50
100
98-100c
98
8
R-CuPc
90
35 × 100c
9
ꢀ-CuPc
105
90
100
10
11
12
13
CoPc
2
15
50
2 × 102
99
4g
4h
FePc
2
105
105
1200
300
50
2.5
99
ClAlPc
2
50
10
99
pyridine
0.2
d
e
a After 300 min 1 is regained quantitatively and unchanged. b Pc ) Phthalocyanine. c 100 batches under the same conditions as entry 7. d 1 drop (10 mg) of pyridine added
to 5 g of liquid 1 causes an abrupt decomposition. e Products could not be analyzed.
Table 2. Thermal control of Scheme 2 with 2 mol %7 of 4h:
volume flow of phosgene produced from 10 g of triphosgene
entry
reaction temp [°C]
volume flow of 3 [mL/min]
14
15
16
90
100
115
6.3
11.5
44.8
reaction rate perfectly adapted to the rate of consumption of
phosgene during the phosgenation in the phosgenation reactor
(Figures 2 and 3). Thus the actual amount of phosgene mainly
originates from the volume (wake space) of the generator, which
should be kept as small as possible. Hence a maximum of safety
can be provided to the user. Thus, amounts of 1 g up to 5,000
g of triphosgene per batch have been converted into phosgene.
Another simplified application of the process is the con-
trolled, internal in situ generation of phosgene from triphosgene
Figure 3. Typical glassware standard equipment for the safety
phosgenation with phosgene supply from triphosgene: (A)
phosgene generator (V ) 1 L, T ) 85 °C) loaded with 600 g of
triphosgene; (B) refluxer (water cooled, T ) 15 °C); (C)
phosgene line (Viton hose); (D) phosgenation reactor (V ) 10
L, T ) 110 °C); (E) refluxer (cryostat cooled, T ) -30 °C); (F)
off-gas line (Viton hose) from the top of the refluxer (E); (G)
cooling trap (dry ice cooled, T ) -60 °C); (H) off-gas line; (I)
cryostat. The assembly of the equipment is somewhat reduced
to effect more clarity of the ensemble.
by 4a-4h within the phosgenation reactor (Figure 4) with the
same advantage of balanced phosgene generation as in the
external device. In this modus the most appropriate catalyst is
4b, because it can be best filtered off. Constrictions could take
place when nucleophilic reagents as (most) amines react very
fast with triphosgene and thus great excesses of phosgene are
formed. The solvent might dissolve the gas, but this is no longer
a safety phosgenation. In these cases the external phosgene
generator would be indicated (see above, Figure 2).
Figure 1. DSC of the conversion of triphosgene to phosgene.
Triphosgene with 1.5% r-CuPc, T ) 10 °C/min.
Experimental Section
IR: Perkin-Elmer 177 Grating Spectrometer. 13C NMR:
Bruker AM 360 Spectrometer.
Compounds 1 and 4a-4 h are commercially available
products from Sigma-Aldrich, with the following purities:
Figure 2. Device for the safety phosgenation with external
phosgene supply from triphosgene in separate flasks.
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begins to evolve. When all of 1 is molten, a constant flow
of 3 emerges until the reaction has ended. Along the way
the reaction temperature rises to a constant 90 °C, and
initially sublimed 1 is washed back to the vessel by
intermediately generated liquid 2, which has been carried
away with the flow of 3. The reaction ends after 35 min,
and dry 4d remains at the bottom of the vessel and can
be reused in the next run. Now the vessel thermometer is
replaced by a gas inlet and nitrogen is blown slowly
through the device for 1 min to carry over remaining
(gaseous) 3 into the cooling trap. CAUTION: The cooling
trap, containing liquid 3, is disconnected from the Viton
hose and the off-gas line, taken out of the dry ice bath,
quickly wiped off the acetone, and immediately weighed
within the hood neary the air suction hole by putting the
charged cooling trap into an adapted foamed plastic form
on the scale of the weighing machine. Yield is 100% (100
g,9 1 mol) of 3, and the purity is >99% (IR, νCdO 1827
cm-1).3e To clean the equipment, hoses, reaction residues,
and all other items, which have been contaminated with
phosgene or triphosgene, are treated with ethanol for at
least 15 min. The alcoholic waste is disposed of as
chloride-containing organic solvent decay.
Figure 4. Device for the safety phosgenation with internal
phosgene supply from triphosgene in the same flask.
The above procedure can be analogously used for phos-
genation reactions according to Figures 2 and 3. Important is
the use of a dry ice cooler at the top of the vessel (could also
be a refluxer with a connected cryostat, cooling medium
temperature below -30 °C), so that phosgene cannot pass off
at all.
Figure 5. Device for the production of safer phosgene from
triphosgene.
1, 98% (IR νCdO 1820 cm-1 13C NMR δ 108.0, 140.9);
,
4a, 98%; 4c, n.a.; 4d, 99%; 4e, 97%; 4f, 97%; 4g, 90%;
4h, 85%.
Conclusion and Outlook
Working with Phosgene. In this section phosgene will
be generated and handled in a range of 100 g, i.e., 22 L
of toxic gas with a TLV of 0.1 ppm. Therefore special
safety precautions have to be arranged. All work with
phosgene has to be carried out in a hood with a strong
exhaust on the highest level. In the hood frontside has to
be placed a COCl2 gas monitor, TLV 0-10 ppm.10 Persons
who work in the laboratory must wear a badge with a
colorimetric COCl2 dosimeter sheet.10 Inside and outside
the laboratory a gas mask with filter B (acid gases) must
be accessible. The gas mask has to be borne when working
in the hood. The sliding window(s) of the hood must fully
be closed. When the gas monitor alerts, switch off heating
bath(s) and leave the laboratory. Then follow the material
safety data sheet and the safety regulations of your
institution.
Safer Production of Phosgene from Triphosgene on a
Molar Scale. (Table 1, entry 7; Figure 5) In a hood with
a powerful exhaust a 250 mL two-necked vessel fitted with
thermometer and magnetic stirrer is charged with 100 g
(0.337 mol) of 1 and 1.15 g (0.002 mol) of 4d. To the
top neck of the vessel is adapted a refluxer, which is
connected upside with a Viton-hose to a 250 mL cooling
trap, which ends in a drying tube and an off-gas line into
the exhaust. The equipment is flushed with dry nitrogen,
and the cooling trap is submerged into an acetone-dry
ice bath. The phosgene generator is heated by an oilbath
(bath temperature 100 °C). When some of 1 is molten, 3
The presented catalyzed process has the capability to produce
phosgene from the solid and safe precursor triphosgene, with
some outstanding properties and advantages:
1. The process transforms solid triphosgene (safe in
transport and storage) quantitatively into phosgene by
a thermally controlled reaction.
2. Contrary to the exothermic phosgene production from
chlorine and carbon monoxide, the phosgene genera-
tion reaction from triphosgene runs without any
reaction heat and thus a thermal runaway is impossible;
in addition, the process guarantees an emergency stop
by cutting off the heat.
3. The process fulfills the criteria of “safety phosgenation
on demand of consumer”: the rate of phosgene
generation is adjustable to the rate of the consumer
reaction by thermal control.
4. The process provides pure phosgene gas without any
solvent, and thus there is no reservoir of phosgene within
(8) (a) Leznoff, C. C.; Lever, A. B. P. Phthalocyanines, Properties and
Applications; VCH: Weinheim, NY, 1989. (b) Lever, A. B. P. AdV.
Inorg. Chem. Radiochem. 1965, 7, 28–114. (c) Ebert, N. A.; Gottlich,
H. B. J. Am. Chem. Soc. 1952, 74, 2806.
(9) The weighing error of this procedure mainly comes from icy condensed
humidity at the cool glassware of the cooling trap and is less than
0.5 g, determined by a series of weighings under the same conditions,
the same equipment, temperature (T )-78 °C), and handling time
<10 s, but without 3. Under these conditions evaporation of 3 (bp 8
°C) hardly ever happens and can be ignored.
(10) Monitox plus gas monitor (COCl2) and phosgene badges from
Compur http://www.compur.com/gasmessgeraete/front_content.
php?idcat)7&changelang)3.
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a great excess of volatile (and highly inflammable)
solvent, which volatilizes this phosgene reservoir in the
case of the equipment’s accidental destruction.
Acknowledgment
The thermochemical data of triphosgene and its conversion
into phosgene with a differential scan calorimeter (DSC) were
thankworthy accomplished by Novasep AG, Dynamit Nobel
GmbH, Leverkusen, Germany. Technical support on the
analytical data about the purity of phosgene according to ref
3b was given by L. Cotarca.
5. Many synthetic chemists need phosgene but do not
like gas bottles and bombs of phosgene or chlorine
and carbon monoxide standing around in their labo-
ratories. They can use avantageously the process to
produce phosgene gas from solid triphosgene. The
engineering and technology company Buss Chem Tech
recommends the process for phosgene uptake rates up
to 30 kg h-1 under semi-industrial conditions.5b Within
this range the production of safer phosgene from
triphosgene is even more cost-efficient than from
chlorine and carbon monoxide.
Received for review September 1, 2010.
OP100239N
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