Facing the unknown with confidence:

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1 HAZARDOUS REACTIONS ALINE DEVOILLE 1, JAN HALLER 2 1. Groupe Novasep, Site Eiffel BP 50, 82, Boulevard de la Moselle, Pompey, France 2. Novasep Leverkusen site (Dynamit Nobel GmbH Explosivstoff und Systemtechnik), Kalkstraße 218, Leverkusen, Germany Aline Devoille Jan Haller Facing the unknown with confidence: working with unidentified hazardous properties of chemical reagents KEYWORDS: assessment of hazardous property, safe handling practices, industrial scale, structure analysis, energetic functionalities, Differential Scanning Calorimetry (DSC), BAM fallhammer test, BAM friction test, Koenen test, Togni s reagent II, 4-hydroxy-1,2,3- benzotriazin-4(3h)-one. The data available on chemicals are not always complete enough for a full assessment of their properties. AbstractHowever, a careful study of the functionalities present in the molecule can often highlight the potential for hazardous properties and suggest the need for further investigation. General rules and common motifs that should alert the chemist are discussed. For compounds suspected of bearing hazardous properties, a typical testing process is presented; the different experiments and their interpretation are described. This approach helps to establish safe handling practices and is illustrated with two case studies. OUR INTENTION Every industrial process benefi ts from experience. Natural common sense is fi ne-tuned by what is done well, and there is no domain where this is truer than in the treatment of hazardous chemistry. The following points and suggestions come out of experience and common sense coupled with years of expertise in the handling of highly energetic compounds at the Novasep facility previously known as Dynamit Nobel GmbH Explosivstoff und Systemtechnik. This discussion is intended to provide the reader with general rules and good practices that need to be observed when treating hazardous chemistry, but it cannot be considered exhaustive. In case of doubt, or to obtain further advice on specifi c cases, the authors highly recommend contacting experienced specialists in highenergy compounds. INTRODUCTION Some chemical reagents could have unidentified hazardous properties which might lead to dangerous situations if not treated correctly, especially when these are used on a large scale such as in the context of industrial production. This article will review some of the current knowledge on this subject, looking at certain chemical structures and motifs that should act as a warning, raising concern about the potentially explosive nature of these compounds. A selection of tests used in determining the explosive nature of these compounds will be discussed and two case studies will be presented where hazardous properties were discovered for chemicals involved in industrial projects at Novasep, offering insights into the determination of these properties and their successful management. WHEN THE MATERIAL SAFETY DATA SHEET (MSDS) DOES NOT TELL ALL It is important to be aware that the MSDS does not always feature complete information on a given compound because all tests are not carried out, leaving some properties unknown. Most chemists handle a wide range of chemicals with a variety of properties on a daily basis. Safety assessments are established and precautions are taken for their handling using the Material Safety Data Sheets (MSDS). MSDS are established on the basis of available information with the goal of helping ensure that these chemicals are handled in a safe manner. While it is the responsibility of the manufacturer or supplier to test for these properties, certain hazards might remain unknown. For this reason, care should always be taken when handling chemicals. Beyond the known properties, the chemist s know-how, common sense and sense of observation are essential and should contribute to building an effective safety net. Often, the enlightened analysis of the chemical structure provides hints and indications of the potential level of danger of these compounds; an alert that further testing is required. Chimica Oggi - Chemistry Today - vol. 32(3) May/June

2 Remember to take into account which chemical structures and motifs should raise concern about the potentially explosive nature of certain compounds Some chemical functionalities or motifs are well known, recognized as promoting explosiveness in chemicals. The most common of these motifs are presented in Figure 1. Many potentially hazardous motifs contain nitrogen, like the famous nitro compounds, but others, for instance, such as peroxides, acetylenes or halogen-oxygen compounds, can also be seen as high-energy compounds, raising our level of attention in their safe handling. It is clear, however, that functionalities or motifs presenting N-O or N-N bonds with a high ratio of nitrogen to carbon or oxygen should raise the concern of the chemist, as they tend to provide an explosive character to the molecule. DESCRIPTION OF THE GENERAL PROCEDURE TO TEST HAZARDS ASSOCIATED WITH A COMPOUND A general flow chart of tests to carry out with a description of a few standard tests The assessment of hazards associated with a given compound consists of a series of tests to observe its behavior towards different stresses (these tests can be found in the United Nations manual for tests and criteria (3). An example of a simplifi ed experimental schema is illustrated in Figure 2. A very fashionable example is azides. These chemicals are widely used in the life sciences industry to carry out clickchemistry reactions as an effi cient route to 1,2,3-triazoles or for the conjugation of two moieties. Azides, in particular small organic ones, are potentially hazardous due to their explosive properties (1). They have to be handled carefully, especially on an industrial scale. As a fi rst approach, key considerations need to be taken into account: the basic guidelines stated by Peer are usually accepted as a good fi rst approach (2). Amongst other precautions, Peer cites the rule of six which states that molecules presenting at least six atoms of carbon (or atoms of similar size) per energetic functionality (such as those listed in Figure 1) should present a suffi cient dilution in order to be relatively safe to handle. In addition, the accumulation or combination of high-energy functionality increases the potential danger associated with it. Highly energetic functions attached to olefi nic or aromatic groups constitute an exception to this rule of six. Extra-care should always be taken with these types of compounds. In general, all these motifs should raise the level of concern: empirical rules and predictions cannot assess accurately the energetic profi le of a given compound. Further studies need to be carried out on those compounds which feature these motifs in order to ensure their safe handling conditions. Figure 2. Simplifi ed fl ow chart illustrating a series of typical tests carried out to assess the hazardous properties associated with a compound with critical structural elements (this is a simplifi ed version of an exhaustive fl ow chart developed at Novasep. Property of Novasep, all rights reserved). The initial series of tests to assess the behavior of a chemical towards stress includes: - Differential Scanning Calorimetry (DSC) to establish the energetic profile (thermal stability) - BAM fallhammer test (or an equivalent test) to assess impact sensitiveness - BAM friction test (or an equivalent test) to assess friction sensitiveness Note that for those substances which are neither shock nor friction sensitive, the tests are typically complemented by a Koenen test. A compound can be classified as non-explosive only when all three tests are negative, however, when one or more tests are positive complementary tests might be needed for a full classification. Figure 1. Example of common motifs promoting explosiveness. These tests will be described below, followed by two case studies illustrating their use in assessing the properties of two different compounds, one of which, Togni s reagent II, was recently discovered to have hazardous properties (4). 48 Chimica Oggi - Chemistry Today - vol. 32(3) May/June 2014

3 In DSC the study sample and reference material are placed in a furnace and gradually heated. The difference of heat flow between the sample and the reference is recorded and this data is then plotted versus temperature to obtain a thermogram. The decomposition of the study sample upon heating generates a peak in the thermogram allowing for the identification of the decomposition onset temperature (where the peak starts rising), the kinetics of the decomposition reaction (narrow peaks correspond to rapid decomposition) and the energy released during the reaction (the area under the curve is proportional to the reaction enthalpy). In short, a sharp, high peak corresponds to a sudden and violent decomposition, meaning that the sample is expected to release a significant amount of energy within a small temperature range, typical of an explosion. A low onset temperature indicates that this decomposition is triggered by only a small amount of energy; i.e., the material is very sensitive. Thus, DSC already indicates whether the compound is expected to be explosive, and if it is likely to be an explosion propagator. The substance is classified as explosive if the gases cannot escape the bore hole fast enough and the tube is ruptured into not less than three pieces in at least one out of three experiments (fragmentation pattern F, G or H ) (5). Samples that are not friction or shock sensitive but exhibit an exothermic pattern in DSC and are negative for the Koenen test are less reactive than the compounds corresponding to the examples cited above. These compounds are not classified as explosives, but further tests (burning test, flash point, time/pressure test, etc.) should still be carried out to fully assess their behavior. Shock sensitivity is measured by carrying out a BAM fallhammer test. A known weight is dropped from a known height on the study sample (i.e., the impact energy is known). If an explosion is audible (i.e., a sound louder than that in a blind test), or flames or sparks are observed, the test is considered as positive. Additionally, the resulting sound can be recorded and analyzed using sound frequency analysis. The recorded sound pressure is compared to the reference of the setting used: any recording over the reference is considered positive. The experiment is repeated six times. If there is one positive result in these six repetitions, the substance is considered explosive. The BAM friction test measures the sensitivity of the sample to friction. The sample is placed on a porcelain tile and a friction of known force is applied using a porcelain peg. The experiment is repeated six times. If there is one explosion with a bang or cracking sound, or the observation of flames or sparks during the six repetitions, the substance is considered explosive. A substance exhibiting friction and/or shock sensitiveness is classified as a Class 1 explosive and has to be handled accordingly. Substances that are neither shock nor friction sensitive but exhibit an exothermic behavior in DSC need to be further qualified. In particular, if the decomposition energy is above 500 J/g a Koenen test should be carried out (as described in Figure 2). The Koenen test examines the behavior of heating under partial confinement (this test needs to be carried out in an explosion-proof chamber). A 27 ml study sample (solids are compacted) is placed in a tube and then covered by a plate with an orifice of typically 2 mm in diameter. The sample is then heated with four Bunsen burners (Figure 3). The results are classified in nine different patterns ranging from 0 to H with 0 indicating no deformation of the test tube, A with deformation of the bottom of the tube, up to G and H where the tube is ruptured into many small fragments with the highest effect, H showing the closing device itself destroyed. Figure 3. Top left: Koenen test set-up before use. Top right: An ongoing experiment with the set-up being heated by Bunsen burners. Bottom: Fragments resulting from the experiment carried out using 4-hydroxy-1,2,3-benzotriazin-4(3H)-one. This shows a test result with an F fragmentation pattern, where the explosion resulted in at least 3 pieces. Case Study 1: Togni s reagent II (4) Togni s reagent II, 1-(trifluoromethyl)-1,2-benziodoxol- 3(1H)-one, is a versatile reagent for the electrophilic introduction of trifluoromethyl groups used in pharmaceutical manufacturing as well as in universities. Tests were carried out at Novasep to examine the energetic properties of both this compound and the intermediates in its synthesis (Figure 4). The first intermediate, while not found to be explosive was highly flammable and quickly deflagrating in the time/pressure test. Togni s reagent II, however, was found to have a positive reaction in the Koenen test (Table 1), showing an F pattern. This compound also exhibited fast combustion when ignited (Figure 5), with a combustion factor of BZ6 being measured, the same classification as black powder. A complete study established Togni s reagent II as a class 1.1D explosive. Due to this new classification, Togni s reagent II must now be approved by the competent national authorities. Novasep also informed companies known to market this compound, who then removed the neat compound from their portfolio, selling it only in phlegmatized form. Chimica Oggi - Chemistry Today - vol. 32(3) May/June

4 Figure 4. Synthesis of Togni s reagent II Table 1. Summary of test results for the investigation of the hazardous properties of Togni s Reagent II and 4-hydroxy-1,2,3- benzotriazin-4(3h)-one. * for comparison TNT is positive at 15 J, RDX (hexogen) is positive at 7.5 J - use soft and polished tools - avoid caking and disperse lumps early - impurities may influence the sensitiveness On a larger scale, the transport of explosive compounds and its handling on a production level requires the permission of competent authorities; Novasep is certifi ed for this and is an experienced handler and producer of hazardous compounds. Figure 5. Flammability test with Togni s reagent II Case Study 2: 4-hydroxy-1,2,3-benzotriazin-4(3H)-one One of the starting materials for a synthesis required by a Novasep customer was 4-hydroxy-1,2,3-benzotriazin-4(3H)-one. The compound is also used as a reagent in coupling reactions. Two kilograms were purchased from a small-scale manufacturer and the material was sent to Novasep with a certifi cate of compliance. Figure 6. 4-hydroxy-1,2,3- benzotriazin-4(3h)-one The structure presents a potentially energetic feature: a heterocycle with high nitrogen content (Figure 6). In addition, the structure exhibits a generally unstable N-O-bond. Based on this core structure, the intermediate and the fi nal products were identifi ed as potentially hazardous compounds and were tested accordingly. The 4-hydroxy-1,2,3-benzotriazin-4(3H)-one was found to be borderline, yet positive in the BAM friction test and positive at 10 J in the BAM fallhammer test which, for comparison, makes it more sensitive than trinitrotoluene (TNT). It was noted as well that the Koenen test resulted in an F pattern (Figure 3). The manufacturer was informed of the explosive properties of this starting material. Following this study, catalog vendors now sell 4-hydroxy-1,2,3-benzotriazin-4(3H)-one in solutions only, which makes it less reactive. In general, and similar to other explosive reagents, this compound can be used safely on a small scale, but should be handled with specific precautions: - use small amounts ( 5 g) - use safety shields - avoid open flames and even sparks - do not grind with brute force (if at all) CONCLUSION For over a hundred years, the use of hazardous chemistry has been an essential part of industrial processes. Yet today, even with our current state of knowledge and technology, certain of these compounds, such as the two examples described above, have only recently been shown to have an explosive potential. The lesson is clear: the use of these types of chemistry demand great care and security. Handling chemicals with high energetic profi les requires constant vigilance and specifi c protocols which result from a blend of common sense and expertise. The deep knowledge of these products, their testing and their handling represent the kind of savoir faire that can only come from experience. When in doubt about any process or compound, it is wise to exercise caution, and to turn for advice to an industrial partner with the track record to provide the relevant and necessary data to proceed safely. REFERENCES AND NOTES Part of the content of this paper has been presented at the conference Hazardous Chemistry for Streamlined Large Scale Synthesis, 4-5 Nov 2013, Cologne, Germany. 1. Safe processes and high purity for a high-tech market published in Speciality Chemicals Magazine, Nov issue, p M. Peer, Spec. Chem, 1998, 18, Manual of Tests and Criteria, 5th revision, Manual of Tests and Criteria, United Nations: New York and Geneva, N. Fiederling, J Haller, H. Schramm, Org. Process Res. Dev. 2013, 17, Recommendations on the Transport of Dangerous Goods. In Manual of Tests and Criteria, 5th revision; Part I: Classifi cation Procedures, Test Methods and Criteria Relating to Explosives of Class 1; United Nations: New York and Geneva, 2009; pp 33 ff (section ). 50 Chimica Oggi - Chemistry Today - vol. 32(3) May/June 2014

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