Phosgenations - A Handbook (COTARCA: PHOSGENATIONS O-BK) || Monitoring Phosgene and Phosgene...
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8
Monitoring Phosgene and Phosgene
Substitutes: Analytical Methods
8.1
Phosgene Monitoring
Phosgene is said to be probably the most poisonous gas used in industry. However,
hydrogen selenide is probably a more poisonous gas and methyl isocyanate is certainlya more poisonous vapor (bp 39 �C). Bis(chloromethyl) ether is more poisonous in
the chronic sense (Occupational Exposure Limit, OEL, 1 ppb). Phosgene might,
therefore, be more correctly described as the most poisonous gas used in any sig-
nificant volume in industry [1].
Phosgene is primarily a lung irritant. Because of its low solubility in water,
phosgene reacts only to a limited extent with the aqueous film on the mucous
membranes, so most of the phosgene reaches the pulmonary alveoli. Here, it re-
acts with bases at the blood–air barrier, disturbing the gas exchange. Phosgene
poisoning is often characterized by a delayed onset, which may occur hours after
the initial exposure. Based on symptoms caused by low concentrations, the rec-
ommended threshold limit value (TLV) is set at 0.1 ppm. This standard was estab-
lished for an eight-hour time-weighted average [2, 3]. Phosgene is an especially
insidious material in that human detection levels (about 0.5–1 ppm) are above
those considered safe (0.1 ppm). After repeated exposures, human detection levels
are elevated. In addition, phosgene is heavier than air, and so it accumulates at
floor level.
Irritation of the throat and eyes by phosgene occurs immediately at 3–4 ppm.
Exposure to 20–30 ppm for as little as 1 min may cause severe irritation of the
upper and lower respiratory tract [4, 5], with symptoms including burning throat,
nausea, vomiting, chest pain, coughing, shortness of breath, and headache. Brief
exposure to 50 ppm can be fatal within a few hours. Severe respiratory distress
may not develop for 4–72 hours after exposure, at which point pulmonary edema
progressing to pneumonia and cardiac failure may occur. Phosgene has not been
found to be carcinogenic or to show reproductive or developmental toxicity in
humans.
Operating areas are continuously monitored by a variety of alarm and shutdown
systems. Operating personnel or others using areas where phosgene is employed
usually wear phosgene indicator badges that change color upon exposure. An analysis
Phosgenations – A Handbook. L. Cotarca, H. EckertCopyright 8 2003 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimISBN: 3-527-29823-1
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of casualities among workers exposed to phosgene in the past, as well as the occu-
pational hazard assessment of phosgene, have been reported [6–8].
8.1.1
Laboratory and Kilolab Handling and Monitoring of Phosgene
Because of its corrosivity and high acute toxicity, phosgene should be handled
using the ‘‘basic prudent practices’’, supplemented by additional precautions for
work with compounds of high toxicity. Laboratory personnel intending to use
phosgene should be fully acquainted with its toxicity and reactivity, and the pro-
tective measures associated with this particular type of chemical. In addition, the
workers’ colleagues should be familiar with the hazards and the necessary rescue
and first aid procedures.
Before starting laboratory work with phosgene, it is recommended that the indi-
vidual is equipped with fresh-air breathing apparatus, a bottle of strong ammonia
(or an alternative reagent) for leak testing, and a supply of 10% aqueous ammonia
solution (or 15% sodium hydroxide solution) for decontamination purposes [1].
In particular, laboratory work with phosgene should be conducted in a suitably
effective fume cupboard, and splash goggles and impermeable gloves should be
worn at all times. It is advisable to attach detector tapes (such as filter papers pre-
viously dipped in a solution of 5% 4-(dimethylamino)benzaldehyde and 5% N,N-diethylaniline in ethanol) to the fume cupboard face. Any emission of phosgene
may then be noted from the characteristic color change (yellow to blue). Notices
should be placed nearby to warn that phosgene is being used. All gas bubblers, or
other vessels, through which phosgene has been passed should be labeled so that
other workers are not exposed to the residual phosgene unwittingly [1]. Flow rates
of phosgene gas and amounts of liquid material should be kept to the minimum
practical amount. Vacuum pumps should be protected by solid sodium hydroxide
traps. In the laboratory, gaseous phosgene can be conveniently metered by cali-
brated flow meters of stainless steel construction; electronic mass flow meters are
commercially available for applications where accurate readings are required. It
has been found that flow meters suitable for use with chlorine may also be used,
after calibration, to meter phosgene [1].
Containers of phosgene solutions should be stored in secondary containers, and
phosgene cylinders should be stored in a cool, well-ventilated area separate from
incompatible materials.
In the event of skin contact, immediately wash with soap and water and remove
contaminated clothing. In the case of eye contact, promptly wash with copious
amounts of water for 15 min (lifting upper and lower lids occasionally) and obtain
medical attention. If phosgene is ingested, obtain medical attention immediately. If
phosgene is inhaled, move the person to fresh air and seek medical attention at
once.
In the case of an accidental release of phosgene gas, such as from a leaking cyl-
inder or associated apparatus, evacuate the area and eliminate the source of the
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leak if this can be done safely. Remove the cylinder to a fumehood or remote area if
it cannot be shut off. In the event of a spill of a phosgene solution, soak up the
solution with a spill pillow or absorbent material, place in an appropriate container,
and dispose of properly. Full respiratory protection and protective clothing will be
necessary in the event of a spill or release in a confined area.
Excess phosgene and waste material containing this substance should be imme-
diately deactivated in the hood by treatment with ethanol or ethanolic ammonia.
Aqueous solutions of phosgene should be treated in the fume cupboard with an excess
of 10% aqueous ammonia (or 15% sodium hydroxide solution), and allowed to
stand until all the phosgene has been neutralized before running to drain. Solu-
tions of phosgene in water-immiscible solvents should be destroyed with ethanolic
ammonia. Decontamination of rubber tubing should be carried out by immersion
in aqueous ammonia prior to disposal in sealed plastic bags. An efficient way to
destroy phosgene gas is to catalyze the hydrolysis reaction on a bed of charcoal over
which an excess of water is passing.
To ensure accurate compliance with regulations concerning the laboratory han-
dling of phosgene and the corresponding safety procedures, it is obligatory to con-
sult the national legislations on this matter, such as the recent Toxic Substances
Control Act (TSCA) of the United States, and the various National Laws based on
the EEC Sixth Amendment (Dangerous Substances). The legislation and codes of
practices affecting compressed gases in general (for the United Kingdom) have
been described by the British Compressed Gases Association [1].
8.1.2
Handling and Monitoring of Phosgene in Large-Scale Chemical Processing Plants
Comprehensive safety precautions are essential in facilities in which phosgene is
manufactured, stored, or processed in any way. Techniques to control occupational
exposure to phosgene must be assessed, and major accidents should be prevented,
literally, at all costs. These requirements are enforced by legislation in most in-
dustrial nations. Although the recommended practices are, in part and of necessity,
of a general nature for working with toxic gases, it is imperative that these, or
similar, practices are followed when working with phosgene. Personnel should be
protected from liquid phosgene by protective clothing that is impervious to phos-
gene, and exposure to the gas in concentrations above the recommended limits
should be prevented by the use of suitable gas masks or air respirators.
Owing to the poor warning properties of the gas to the human senses, automatic
continuous monitors equipped with alarm systems are recommended. Skin and
eye contact with phosgene should be avoided, but contaminated clothing should
be removed immediately and decontamination effected by washing. Emergency
showers should be provided in any facility in which phosgene is stored, used, or
manufactured [9]. Personnel engaged in the handling of phosgene should be
trained to recognize its odor and instructed in the application of protective mea-
sures and first aid and emergency procedures [10, 11]. In particular, personnel
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should be made to appreciate the delayed effects following potentially lethal ex-
posures to phosgene.
Requirements for safety and environmental protection in industrial processing
using phosgene supplied on demand of the consumer by the implementation of
‘dynamic’ reactors for its production have been reported (see Section 2.1.2). The
manufacture and delivery of phosgene to the users on demand, without interme-
diate storage, has made it possible to strongly reduce the quantities of phosgene
contained within the plant. Confinement of the phosgene production, supply, and
utilization equipment in a double envelope makes it possible to collect any leakage
with ultimate destruction of the phosgene in specific installations [12, 13].
The following safety measures have been described for phosgene storage and
handling in a plant environment [1].
. Phosgene storage and handling operations should be in a remote location from
the rest of the plant.. Phosgene storage rooms should be provided with an inspection window to per-
mit viewing of the area without the need of entry.. Ventilation switches and emergency protection equipment should be located
outside the storage area in easily accessible locations, which would be uncon-
taminated in the event of an emergency.. Where possible, phosgene should be generated on demand to avoid cylinder
handling and phosgene storage.. Phosgene gas should be used in preference to the liquid material.. The phosgene storage area should be continuously vented to alkali scrubbers.. A system of automatic analyzers should be employed to continuously monitor
the ambient air and all phases of the operation.. Alarms (audible, visual, and valve-closing) should be set to operate automatically
when the concentration of phosgene reaches the sensored limit.. Phosgene should be piped through a double-skinned conduit, such as a pipe
within a pipe. The outer pipe should be continuously monitored for phosgene.
Pipes containing phosgene should be distinctively marked.. Where phosgene is stored in tanks, these should be of a double-shell construc-
tion. Bulk phosgene is preferably stored underground.. Plant hardware that is exposed to phosgene should be composed of high quality
stainless steel, or PTFE, as appropriate.. An extensive preventative maintenance program should be operated to safeguard
against leaks and equipment failure. Potential emission sources should be iden-
tified.. An extensive training program should be implemented and a ‘Phosgene Manual’
should be available.. Dosimeter badges should be worn by personnel who work in the phosgene area.. An emergency/evacuation plan should be established and frequent drills exe-
cuted.. Before equipment is taken out of service, all lines must be purged of any phos-
gene.
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8.2
Analytical Methods
The required analytical range of concentrations for the quantitative determination
of phosgene may vary from the parts-per-trillion (ppt) level to virtually 100%. In
particular, the low exposure limit value for phosgene in air recommended in some
countries (e.g. Sweden, Italy, and Romania have adopted 0.05 ppm, the UK 0.02
ppm) emphasizes the requirement for sensitive, reliable, and specific methods for
its detection. The following analytical methods are currently employed for the de-
termination of phosgene:
1. Volumetric methods: acidimetry, iodometry
2. Gravimetric methods
3. Colorimetric methods: non-automatic (wet and dry techniques) and automatic
4. Argentometric methods
5. Chromatographic methods (gas chromatography and HPLC)
6. Spectrometric methods (IR, UV, MS, NMR, interferometry)
7. Light-scattering and particle detection
8. Electrical methods (electrochemical and electrical conductivity)
An important survey on the above methods is available [1]. The acidimetric
method is not specific to phosgene and is based on reaction according to the fol-
lowing equation:
COCl2 + [ OH] 2 Cl + [CO3]2-
+ H2O4 2
The phosgene can thus be determined by a double-indicator titration, or by de-
termining the chloride ion content of the solution.
The oxidizing property of phosgene is employed for its determination by an
iodometric technique:
COCl2 + I 2 Cl + CO + I22
A less accurate method is based on the quantitative formation of 1,3-diphenylurea
upon passage of the phosgene-containing gas into a cold, saturated, aqueous solu-
tion of aniline according to the following equation:
COCl2 + PhNH2 (PhNH)2CO + 2 [PhNH3]Cl4
The wet or dry colorimetric techniques are based on the reaction of phosgene with
Harrison’s reagent (a mixture of non-aqueous solutions of 4-(N,N-dimethylamino)-
benzaldehyde and diphenylamine) yielding a yellow, orange, or brown color, ac-
cording to the concentration. A more marked color change (yellow to blue) on
exposure to phosgene is observed when N,N-dialkylanilines are coupled to the
above aldehyde.
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CHO
Me2N
COCl2CCl2
Me2N
PhNR2
Me2N R2
Cl
N
The one-time recommended standard (NIOSH) for the analysis of phosgene in
air was based on the use of a mixture of 4-(4 0-nitrobenzyl)pyridine and N-benzyl-phenylamine in diethyl 1,2-benzenedicarboxylate solution, which produces a bril-
liant red color on exposure to phosgene. The absorbance of the sample solution is
usually determined spectrophotometrically at a wavelength of 475 nm, with a con-
centration as low as 5 ppb being detectable.
Infrared spectroscopic methods are particularly suitable for the determination of
phosgene at concentrations below the currently established threshold limit value.
Measurements of low concentrations (25–500 ppb) [14] have been reported. Phos-
gene has strong absorption bands at 849 and 1827 cm�1, but the intensity of the
combination band at 1011 cm�1 is less than one-thirtieth of that at 1827 cm�1.
8.3
Monitoring Chlorinated Equivalents of Phosgene (Triphosgene)
All solid triphosgene has triphosgene vapor associated with it. Phosgene color
badges become colored during the initial opening of any bottle, can, or bag. Pre-
cautions should be taken when handling the solid in order to avoid the uncon-
trolled exposure of the operator. The safety measures should be identical to those
applied for phosgene.
The occupational hygiene effect of triphosgene has not yet been fully deter-
mined. A Consent Order was issued because the substance may present an unrea-
sonable risk of injury to health and a two-year, two-species bioassay test was rec-
ommended [15–18].
In the following, some recommendations are given based on the authors’ experience.No responsibility is taken for any unforeseen result occurring as a consequence of apply-ing the information contained herein. Professional advice should be sought before adopt-ing any of the procedures described.When solid crystalline triphosgene is immersed in water at ambient tempera-
ture, no significant change of pH (HCl release) occurs, and hence no decomposi-
tion into phosgene is observed. This is due to the very low solubility of triphosgene
in water and the slow reaction rate. The situation is different when solvents such
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as tetrahydrofuran or dioxane are used. Water miscibility with such (basic) solvents
is significant, and therefore the reaction between triphosgene and nucleophilic
water can proceed in a homogeneous liquid–liquid system. In this case, tempera-
ture and basic catalysts play important roles in accelerating decomposition.
It is strongly recommended that a Karl-Fischer water analysis is performed on a
solvent before it is used in a triphosgene reaction as solvents can be a source of
nucleophilic water (for example, at 25 �C, the solubility of water in EtOAc is
around 3.3% w/w!). Much of the ‘‘released process phosgene’’ originates from re-
sidual water. Both phosgene and triphosgene are hydrolyzed to HCl and carbon
dioxide. The difference lies in the magnitudes of the reaction rate constants, phos-
gene hydrolysis being a thousand times faster (for phosgene dissolved in a liquid
phase) than triphosgene hydrolysis. Hydrolysis of triphosgene generates phosgene.
The latter reaction is considerably accelerated by the presence of bases and by an
increase in temperature. Under such conditions, the phosgene produced can be
released in the off-gases.
It is for this reason that in the process handling of triphosgene the reaction
mixture must be stringently protected from accidental contact with water or alkali
metal hydroxide solutions (warning on scrubber).
When triphosgene hydrolysis is occurring, one has to consider the effect of
moisture on the reactivity. The bimolecular nature of the process should also be
kept in mind. One has to estimate the amount of water present (i.e. water dissolved
in the reaction solvent containing triphosgene) during those process stages in
which triphosgene can generate phosgene. Theoretically, 18 g of water can destroy
297 g of triphosgene. The generated phosgene would then react very rapidly with
excess water to give carbon dioxide and hydrochloric acid [18].
As regards the preparation of triphosgene solutions, i.e. dissolution of crystalline
triphosgene in a solvent, and the storage of such solutions prior to reaction, any
data concerning the so-called ‘‘hold points’’ and acceptable ‘‘holding times’’ of
such solutions should be useful. Reaction progress is then monitored with partic-
ular emphasis on the off-gases and checking of the scrubber (indeed, the scrubber
effectively becomes a second ‘‘phosgenation reactor’’). Lastly, when it comes to
work-up and final hydrolysis, the product should only be separated when no trace
of phosgene remains.
The standard operating procedures must always include a nitrogen atmosphere
with moderate flushing (with control of the water content in the nitrogen flow).
When an experiment is performed in the laboratory (homogeneous phase or a
biphasic system), phosgene is usually detected in the off-gassing, and in all the
layers (organic, aqueous, reactor cleaning solvent, etc.) after the reaction. The or-
ganic phase can show up to 100 ppm phosgene.
In all cases, aqueous ammonia (as described above for phosgene) should be used
to ‘‘neutralize’’ the phosgene-containing off-gases. Aqueous NaOH is much more
reactive and, at higher temperatures, can decompose triphosgene violently, releas-
ing phosgene. Higher pH does not necessarily guarantee the destruction of phos-
gene in the off-gases; the design of the ‘‘destruction reactor’’ is a more important
question, and its downstream effluent should show 0 ppm phosgene.
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No chromogenic method is available to qualitatively distinguish between phos-
gene, diphosgene, and triphosgene in the liquid phase, at the interface between the
liquid and gas phases, or in the gas phase.
The color reaction of triphosgene with Harrison’s reagent (a mixture of 4-(N,N-dimethylamino)benzaldehyde and diphenylamine in a non-aqueous solvent) yields
a yellow to deep-orange hue, according to the concentration [19].
In the laboratory or in other small-scale operations, specific Draeger tubes are
used to detect phosgene. Information on suppliers of such equipment can be
found on the Internet. The Data Sheet for phosgene badges lists the following posi-
tive interferences: dust, chloroformates, cyanuric chloride, carbonyl bromide; some
phosgene derivatives such as carbonates are also detected. On the other hand, ace-
tyl chloride, oxalyl chloride, chlorine, and very high concentrations of hydrogen
chloride will suppress the response to phosgene.
For the use of the React-IR technique to distinguish between chlorinated equiv-
alents and to monitor triphosgene decomposition, see [20].
For the quantitative determination of triphosgene, the recommended methods
are the same as those for phosgene:
. Colorimetric method: after reaction of 4-(4 0-nitrobenzyl)pyridine and N-benzyl-phenylamine in diethyl 1,2-benzenedicarboxylate, exposure to triphosgene pro-
duces a brilliant red color.. Titration: phosgene and triphosgene liberate iodine from sodium iodide in ace-
tone.. Argentometric titration: titration of the liberated chloride ions after hydrolysis.
For a quantitative determination in large-scale chemical processing, automatic gas
level sensors, such as the OLDHAM-GZ-ARRAS (France) M/42, having a four-
channel programmable alarm system, are used [19]. Electrochemical phosgene
detectors (0.1–3.0 ppm) and handy pumps with phosgene tubes (AUER GAS-
TESTER II) (from 0.1 ppm) are also employed.
8.4
References
1 T. A. Ryan, C. Ryan, E. A. Seddon,
K. R. Seddon, Phosgene and RelatedCarbonyl Halides, Elsevier,Amsterdam, 1996.
2 T. C. Marrs, R. L. Maynard, F. R.
Sidell, Chemical Warfare Agents.Toxicology and Treatment, J. Wiley &
Sons, Chichester, 1996, p. 185–202.
3 A. M. Mehlman, Def. Sci. J. 1987,37(2), 269–279.
4 U. P. Kodavanti, D. L. Costa, S. N.
Giri, B. Starcher, G. E. Hatch,
Fundam. Appl. Toxicol. 1997, 37(1),54–63.
5 B. J. Jugg, P. Rice, D. A. Berg (Eds.),
Proc. ERDEC Sci. Conf. Chem. Biol.Def. Res. 1996, Meeting Date 1994,
205–210, Publisher: National Techni-
cal Information Service, Springfield,
Va.; Chem. Abstr. 1997, 127, 1763.6 A. P. Polednak, D. R. Hollis, Toxicol.Ind. Health 1985, 1(2), 137–147.
7 J. Santodonato, Cent. Chem.
Harvard Assessment, Syracuse Res.
8.4 References 627
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Corp., Syracuse, NY, USA. Avail.
NTIS. Report 1985 (Order No. PB86-
135126/GAR), 32 pp.
8 From: Gov. Rep. Announce. Index
(U.S.) 1986, 86(7), Abstr. No. 613,353;Chem. Abstr. 1986, 105, 231598.
9 M. Sittig, Handbook of Toxic andHazardous Chemicals, Noyes Publ.,Park Ridge, 1981.
10 J. Alspach, R. J. Bianch, Plant/Oper.Prog. 1984, 3, 40.
11 American Industrial Hygiene
Association, Phosgene, Hygienic Guide
Series, Detroit, Michigan, 1968.
12 http://www.davyprotech.com13 R. Delseth, Chimia 1998, 52, 698.
14 G. G. Esposito, D. Lillian, G. E.
Podolak, R. M. Tuggle, Anal. Chem.1977, 49, 1774–1779.
15 EPA No. P 90-1535. Fed. Regist. 56# 156:40204 (13 Aug., 1991).
16 Pesticide Toxic Chem. News 19# 41:20 (14 Aug., 1991).
17 Chem. Regul. Rep. 15 # 20:633 (16Aug., 1991).
18 L. Cotarca, R. Bacaloglu, N.
Marcu, A. Tarnaveanu, J. Prakt.Chem. (Ger-many) 1985, 327, 881–886.
19 Ubichem, Triphosgene, CD-ROM.
20 L. Pasquato, G. Modena, L.
Cotarca, S. Mantovani, P. Delogu,
J. Org. Chem. 2000, 65, 8224–8228.
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