Organic Process Research & Development 2007, 11, 1131–1134
Communications to the Editor
Safety Evaluation of an Unexpected Incident with a Nitro Compound
Rafael Barbas,‡ Manuel Botija,† Helena Camps,† Anna Portell,‡ Rafel Prohens,*,‡ and Cristina Puigjaner*,‡
Moehs Ibérica S.A., César Martinell i Brunet 12, 08191 Rubí, Barcelona, Spain, and Plataforma de Polimorfisme i
Calorimetria, SerVeis Cientificotècnics, UniVersitat de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain
Abstract:
An unexpected highly exothermic reaction followed by explosion
has been studied by means of reaction calorimetry and adiabatic
calorimetry. The investigation of the process shows that the
incident took place by a local adiabatic temperature rise in the
reactor vessel due to the presence of potassium carbonate, which
Figure 1. Synthesis of 2,3-dimethyl-4-(2,2,2,-trifluoroethoxy)
pyridine N-oxide (2).
activated the decomposition of a nitro compound with an unusual
low temperature onset. The study is completed with an improved
and safer procedure consisting of changing the order of chemicals
crucible was used, and a heating rate of 10 °C/min was applied
addition as an alternative approach.
in the DSC experiment. Compound 1 melts at 101 °C and shows
a high severe decomposition beginning at 237 °C, with an
associated heat of 1797 J/g, according to the results obtained
directly from the DSC analysis (Figure 3). An adiabatic
temperature rise of 998 °C has been calculated according to
the equation ∆Tadiabatic ) ∆H/Cp (a heat capacity of 1.8 J/g °C
Introduction
In the past, Moehs Ibérica S.A. has produced Lansoprazol
(a proton pump inhibitor indicated for gastric ulcer treatment)
by a multistep synthesis from 1. One of the intermediates is
2,3-dimethyl-4-(2,2,2-trifluoroethoxy)pyridine N-oxide (2), ob-
has been estimated).
This result suggested the possibility that the other chemicals
tained by condensation of 2,3-dimethyl-4-nitropyridine N-oxide
involved in the reaction mixture might affect the decomposition
(1) with trifluoroethanol in MEK/water using triethylbenzy-
onset of 1, since this value (237 °C) was too high to allow for
lammonium chloride as a phase transfer catalyst (Figure 1).
the quick runaway observed. It has been described that pure
During the production of one batch, an incident occurred
organic nitro compounds decompose at high temperatures,
unexpectedly. The incident happened as follows. The vessel,
exhibiting large exotherms, the reaction being violent or
at room temperature, was first charged with 450 kg of 2,
explosive in most cases. Moreover, reactants, solvents, and
3-dimethyl-4-nitropyridine N-oxide (1), then 720 kg of potas-
impurities may affect organic nitro compounds’ thermal stabil-
ity, lowering their temperature of decomposition.2
sium carbonate and 15 kg of triethylbenzylammonium chloride
(TEBA) were added without stirring, and finally 15 L of water
was added. The incident started 10 min after the vessel was
closed for alternate vacuum/nitrogen purge. A high increase of
the internal temperature associated with fast gas evolution was
detected (24 h after the incident, the temperature was 330 °C),
generating a sudden pressure rise that ended up with the
explosive breakage of the reactor (Figure 2). In view of the
unexpected incident, an investigation was set up to clarify
the origin of the severe system thermal runaway.
Therefore, we investigated the thermal stability of 1 in the
presence of the other chemicals. Since DSC analysis is known
to give results with a relative uncertainty regarding the
decomposition onset as a result of the small sample size and
high heating rates,3 it was important to carry out screening
experiments on a larger sample size. This was done in an
accelerating rate calorimeter (ARC), which offers the possibility
to prepare reaction mixtures, gives a more accurate determi-
nation of the onset temperature of the decomposition and makes
it possible to determine the pressure rise during decomposition,
which finally is what provokes the reactor breakage and
explosion. It was observed that the mixture of 1 with triethyl-
benzylammonium chloride and potassium carbonate, analyzed
by ARC, showed an slow exotherm from 72 °C, which became
extremely fast at 89 °C with an adiabatic temperature rise higher
Results and Discussion
First, we evaluated the reactivity of 1 by differential scanning
calorimetry to determine its explosive potential.1 A sealed
* To whom correspondence should be addressed. Telephone: +34 93 4034656.
E-mail: cris@sct.ub.es and rafel@sct.ub.es.
† Moehs Ibérica S.A.
‡ Plataforma de Polimorfisme i Calorimetria, Serveis Cientificotècnics,
Universitat de Barcelona.
(2) Gustin, J-L. Org. Process Res. DeV. 1998, 2, 27–33.
(3) Steinbach, J. Safety Assessment for Chemical Processes, Wiley-VCH:
Weinheim, 1999; pp 29–26.
(4) Townsend, I. J. Therm. Anal. 1991, 37, 2031–2066.
(1) King, R.; Hirst, R. Safety in the Process Industries, 2nd ed.; Elsevier:
Oxford, 2002.
10.1021/op700128r CCC: $37.00
Published on Web 10/09/2007
2007 American Chemical Society
Vol. 11, No. 6, 2007 / Organic Process Research & Development
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