Chemistry Reference
In-Depth Information
Considering such hazard warnings, the tremendous growth of phosgene-free
methods, including triphosgene chemistry, during the last decades has been sur-
prising, offering to the research laboratories milder and more easily controllable
conditions for phosgenations [16]. Recently, some important contributions to the
control of triphosgene stability have been brought to the attention of the chemical
community [80]. Quantitative experimental data, that have allowed hazard and
safety guidelines on triphosgene usage in organic processes to be drawn up, are
available [11-20, 69, 80, 90].
When solid crystalline triphosgene is immersed in water, no significant change
of pH (HCl release) and hence no decomposition into phosgene is observed. This
is due to the very low solubility of triphosgene in water. The behavior and con-
sequences are different when solvents such as THF or dioxane are used. These are
significantly miscible with water, and hence the reaction between triphosgene and
nucleophilic water can take place in a homogeneous liquid-liquid system. In this
case, temperature and basic catalysts play important roles in accelerating the de-
composition. For this reason, in processes involving the handling of triphosgene in
an organic solvent, the reaction mixture must be rigorously protected from acci-
dental contact with water or NaOH solution (e.g. that in the scrubber).
Nucleophilic substitution at triphosgene starts with a solvation process [14]. It is
supposed that, before any nucleophilic attack, several molecules of the nucleophile
first have to become associated with triphosgene in the transition state. In evaluat-
ing triphosgene hydrolysis, the effect of moisture on the reactivity must be eval-
uated. One has to estimate the amount of water present (i.e. water dissolved in the
reaction solvent containing triphosgene) during those steps of the process in which
triphosgene can generate phosgene. Theoretically, 18 g of water can react with 297
g of triphosgene. Therefore, operation in an open reactor must always be avoided
and standard operating procedures must always include nitrogen atmosphere and
moderate flushing (with control of the water content in the nitrogen flow).
For example, Ubichem, UK, developed a novel process for producing triphosgene
several years ago, and carried out extensive tests to determine its stability in the
presence of various impurities [91, 92]. Such studies are, of course, imperative to
identify the appropriate materials for plant construction, the appropriate pack-
aging, and the appropriate handling in use.
It was found that triphosgene is indeed unstable in the presence of partially
chlorinated intermediates, metal ions, charcoal, and nucleophiles (the source of its
reactivity). Detailed analyses of several marketed products have been carried out and
significant levels of partially chlorinated dimethyl carbonate have been found. The com-
pound was also shipped in metal drums. The effect on stability was obvious: HCl and
phosgene were immediately detected in the head space of the drum. The same company
now has triphosgene made under contract in an entirely glass/poly(tetrafluoro-
ethylene) system, and packs the material in a PTFE container that is then over-
packed in a sealed heavy-duty foil laminate sachet. This sachet is designed to
withstand high temperatures, and it is specifically employed to minimize the re-
lease of triphosgene breakdown products in the event of a transport accident
[91, 92].
