Process Safety Considerations for the Use of 1 M Borane

Subscriber access provided by UB + Fachbibliothek Chemie | (FU-Bibliothekssystem)

Full Paper

Process Safety Considerations for the Use of 1 M Borane Tetrahydrofuran Complex Under General Purpose Plant Conditions Alexandre Monteiro, and Roy C Flanagan Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.6b00407 • Publication Date (Web): 12 Jan 2017 Downloaded from http://pubs.acs.org on January 12, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Organic Process Research & Development is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Organic Process Research & Development

Process Safety Considerations for the Use of 1 M Borane Tetrahydrofuran Complex Under General Purpose Plant Conditions Alexandre M. Monteiroa,* and Roy C. Flanaganb,* a

Process Safety, GlaxoSmithKline R&D, Collegeville, PA 19426 b

Process Safety, GlaxoSmithKline R&D, Zebulon, NC 27597

ACS Paragon Plus Environment

1


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 23

TOC Graphic


2

Page 3 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ABSTRACT: The safe handling of 1 M borane tetrahydrofuran complex (BTHF) in the context of storage and shipping has been well characterized in literature. However, its safe use within the context of general purpose plant conditions is not discussed in detail. This article evaluated the thermal stability of BTHF within the context of general purpose plant equipment at near reflux and explored the diborane evolution – BTHF temperature relationship utilizing reaction calorimetry and headspace mass spectroscopy. In addition, a review of the autoignition temperature (AIT) for diborane reported in literature was performed and new data was generated using the current ASTM (E659) standard. The testing showed that the AIT of pure diborane in air is 136-139 °C. An enhanced basis of safe operation for using BTHF in general purpose plant was established.

KEYWORDS: Process safety, diborane, boranes, borane tetrahydrofuran complex, mass spectroscopy, autoignition temperature


3


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 23

INTRODUCTION Borane complexes have proven to be useful reagents in the fine chemical industry, offering chemists similar advantages to diborane without most of the storage and handling concerns of a pyrophoric gas. Of the available complexes, borane tetrahydrofuran stabilized with sodium borahydride (BTHF) has remained a popular choice due to its reactivity versus some of the more concentrated complexes (e.g. borane-dimethyl sulfide)1. Tetrahydrofuran, as a weak Lewis base aids the reactivity of BTHF, but it is also the primary cause of thermal stability issues exhibited at higher concentrations and temperatures. While the formation of concentrations greater than 1 M BTHF is possible2,3, concentrations higher than 1 M are no longer commercially available following an explosion at Pfizer’s research facility in Groton, CT4. Moreover, even the 1 M concentration is not without incident, with accidents detailed in Bretherick's5. In light of the issues associated with the use and storage of 1 M BTHF, a significant body of work has already been performed. A literature review on the use of 1 M BTHF at higher temperatures finds numerous studies detailing the stability of 1 M BTHF and discussions around the temperature-decomposition reaction pathway relationship3,6-8. Researchers note that below 50 °C, THF is susceptible to ring-opening leading to the formation of tributoxyborane while above 50 °C, the formation and evolution of diborane takes place. The majority of published work focused on the stability of BTHF at higher temperature and the shipping of sealed containers per United States Department of Transportation regulations. Accordingly, all of the studies cited investigated the stability of BTHF in sealed containers (e.g. sealed NMR tubes). While shipping and storage of reactive materials is an important aspect in chemical processing, additional key considerations are necessary in evaluating the hazards of using this reagent in general purpose


4

Page 5 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


manufacturing facilities. During the process risk assessment, controls are established to mitigate these hazards and ensure a basis of safety can be established. To the best of the author’s knowledge, no study has been undertaken that investigates the stability of BTHF under general purpose plant conditions, which typically include the sweeping of reactor headspace using an inert gas. Furthermore, while the formation of diborane above 50 °C has been noted, the risk of forming higher boranes from the decomposition of BTHF has never been explored. These compounds, being less stable and more reactive than the borane complex, can have a significant impact on the basis of safe operation9,10,11. An objective of the current study is the investigation of the thermal stability of 1 M BTHF under standard plant conditions utilizing reaction calorimetry and headspace mass spectroscopy to help elucidate the decomposition products at higher temperatures and determine the feasibility of forming higher boranes under normal reaction conditions. Furthermore, during the preparation of this manuscript, discrepancies in the reported autoignition temperature (AIT) for diborane were noted when an extensive literature review on the subject was performed. As a result, an additional objective to resolve these discrepancies emerged; and, we wish to report updated technical information on this important element of scientific literature.

RESULTS AND DISCUSSION Within the pharmaceutical industry, manufacturing of active pharmaceutical ingredients (API) is primarily still performed in the batch or semi-batch fashion, utilizing stirred tank reactors ranging from 30 to 2000 gallons. The use of large amounts of reactive reagents within the process, often in excess, comes with numerous risks such as decomposition and side reactions which may lead to additional hazardous compounds. Within a general purpose plant, reaction vessels are usually operated under atmospheric pressure and utilize an inert gas sweep to ensure


5


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 23

the vessel headspace remains oxygen free. These vessels are then vented into a common header shared by other vessels in the plant. Therefore, understanding the identity and quantity of reactive, flammable, toxic, and/or pyrophoric gases being generated within a process is crucial, either as part of the desired reaction, undesired decomposition, or side reaction. Process safety and plant engineers must understand and have a handle on these risks to establish and maintain a basis of safety. When using BTHF in a general purpose plant, the major concerns are thermal stability of the complex, typically used in excess, and the generation of diborane at elevated temperatures. In the following sections, a detailed discussion around the stability of BTHF at elevated temperatures and an interrogation of BTHF decomposition products, both in solution and as evolved gases, is presented. This data is critical in establishing an enhanced basis of safety when using this common reagent. Diborane and its Autoignition Temperature. In the three decades following the pioneering work of Stock11 on lower hydrides of boron, an enormous amount of activity in the United States focused on exploration of diborane as a fuel source for the emerging jet propulsion industry. The activity culminated in the late 1950’s with diborane being produced on multi-ton commercial scale by several chemical companies contracted by the U.S. government. However, the industry was fraught with numerous accidents and multiple fatalities, as documented by Dequaise in his book The Green Flame12. The numerous accidents involving the use of diborane ultimately resulted in the program being abandoned in the early 1960’s. The challenges and dangers of handling this pyrophoric gas were well known to early researchers. Mellor, citing the early work of Stock, reported that the condensed liquid readily decomposes and explodes when exposed to air13. With the increased focus and funding available


6

Page 7 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


to support diborane research during the rocket program era, a significant amount of effort was spent on better defining the flammability characteristics of diborane to enable safe handling and storage, using more modernized laboratory techniques. Working at the General Electric Company’s laboratory, Price determined that the lowest temperature of spontaneous ignition for diborane-oxygen mixtures was between 130 to 135 °C14. Contemporaneously, Whatley and Pease reported results in general agreement, with explosion of diborane-oxygen mixtures occurring in the range of 105 to 165 °C15. Callery Chemical Company summarized the work of these and other researchers, reporting that diborane mixtures with air or oxygen do not spontaneously ignite at room temperature; and, heating above 100 °C causes explosion, likely due to the formation of unstable decomposition impurities16. In 1971, the National Aeronautics and Space Administration (NASA) issued the definitive Diborane Handbook, which documents an ignition temperature for diborane in oxygen and air at 135 °C and 145 to 150 °C, respectively17. However, the report also states that diborane should be regarded as pyrophoric at room temperature, given the unreliable flammability characteristics as a function of impurities and other factors. Given the overwhelming amount of scientific literature which established an autoignition temperature (AIT) of >100 °C, it is unclear to the authors why this value is reported ubiquitously in modern reference works as 38 to 52 °C18,19. Following an exhaustive literature review to determine the earliest reporting of these lower values, a citing appeared in the National Fire Protection Association (NFPA) circular in the early 1960’s, reporting an ignition temperature of 100 to 125 °F20 (38 to 52 °C). The reference also stated that diborane may ignite spontaneously in moist air at room temperature. Given the history and high profile of this organization in establishing safety standards within the U.S. workplace, particularly with respect to handling


7


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 23

hazardous chemicals, it is likely to be the source of the modern, low-temperature AIT reporting. Contacting the NFPA archival department did not shed any further light on the subject, as reported information (data, methods, etc.) from that time period is no longer available. Unfortunately, this data has a significant, and restrictive, impact on establishing a basis of safety for processes where diborane is used or generated. In an effort to solve this contradiction, the authors sought to determine the AIT of diborane, using current testing standards. High purity diborane was obtained from Voltaix Corporation (Branchburg, NJ) and Fauske & Associates (Burr Ridge, IL) was commissioned to perform the testing according to ASTM (E659) standards. The testing showed that the AIT of pure diborane in air is 136-139 °C21. Moisture levels, ranging from 25-75% relative humidity, appear to have very little impact on the AIT. The findings essentially verify the work of Price, and others, from over 50 years ago. While it is unlikely that the new information will replace the misinformation omnipresent in current literature, it is an important aspect in establishing a basis of safety for this work and the chemical industry going forward. Of particular note in this reporting is the role of diborane purity, as it is likely the case that lower reported values for AIT were the result of premature ignition caused by presence of unstable impurities; namely, higher boranes17. BTHF Thermal Stability. Long22 published an extensive investigation detailing the mechanisms for decomposition of diborane, leading to the generation of higher boranes. Following his work, a series of experiments were performed to determine the presence of higher boranes generated during the decomposition of BTHF, including diborane. To generate diborane, a known amount of BTHF was charged to a clean/dry 1 L reaction calorimeter coupled to an inline mass spectrometer and thermal mass flow meter. The mass spectrometer was programmed to scan for hydrogen, diborane, and tributoxyborane in the headspace, and BTHF was heated to


8

Page 9 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


55 °C and aged for 24 hours. Diborane and hydrogen gas were observed during the heat-up period, peaking shortly after the temperature reached 55 °C, before beginning a gradual decline as the age period progressed. Tributoxyborane was observed in trace amounts throughout the experiments once the heat-up commenced. Most notably, the formation of diborane and hydrogen was observed at temperatures as low as 5 to 10 °C during the heat-up period. The presence of diborane at such low temperatures was surprising, since previous studies3,6-8 in closed systems noted diborane would only form at temperatures above 50 °C. It’s likely that the presence of an inert sweep over the headspace, which removes any diborane evolved from solution, leads to the evolution of additional diborane as the system strives to maintain equilibrium between diborane in solution and diborane in the headspace. To test this hypothesis, the amount of BTHF charged to the reaction calorimeter was increased and the amount of diborane and hydrogen evolved was measured by integrating the combined thermal mass flow meter and mass spectroscopy data. As shown in Table 1, the total amount of diborane and hydrogen gas evolved decreased when the headspace volume decreased (i.e. the amount of BTHF charged increased). Table 1. MS and GC Results from BTHF Aging Studies Run

Temp (°C)

BTHFa

B 2H 6b

H 2b

1 2 3 4

55 55 55 55

0.371 0.357 0.704 0.705

5.652 5.457 4.192 4.203

6.020 7.480 5.102 5.115

Tributoxyboraneb Tributoxyboranec 0.102 0.096 0.084 0.108

42.6 44.2 48.1 50.6

Dibutoxyboranec 32.7 30.2 38.5 39.0

a

Total amount of 1 M BTHF charged to reactor [kg]. bTotal Gas observed via headspace mass spectroscopy [L/kg BTHF]. cTotal amount in aged solution via GC analysis [g/kg BTHF]

Since the reactor system was dry and inerted, the presence of hydrogen gas not only confirms BTHF is decomposing to form diborane at temperatures from 5 to 55 °C, but that diborane itself must be reacting/decomposing to form other borane species. Based on Long’s work22, a search


9


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 23

for these was performed using mass spectroscopy. Namely, tetraborane (48 m/z), pentaborane-9 (B5H9, 59 m/z), and hexaborane (71 m/z). Over multiple experiments, tetraborane and hexaborane peaks were never observed above baseline levels; however, the peak potentially associated with pentaborane-9 was observed at low levels, particularly during the heat-up period. In order to determine the actual presence of pentaborane-9, additional work was required. In line with Bragg et al.23, mass spectroscopy may be used to distinguish between pentaborane-9 and pentaborane-11 (B5H11) by comparing the ratio of m/z peaks 61 and 59. A ratio of 1.05 indicates pure pentaborane-11 while a ratio of 0.63 indicates the presence of pure pentaborane-9. When we looked at the signal at 61 m/z, we never observed the value above baseline noise level, indicating the peak signal observed at 59 m/z was neither pentaborane-9 or pentaborane-11. Instead, the signal observed was likely associated with tributoxyborane, which has a known contribution at 59 m/z. While the dibutoxyborane mass spectrum is not available in the literature, it is likely that this species also contributes at 59 m/z, given the similarity in structure. The appearance of an approximately equimolar amount of hydrogen, relative to diborane evolved, was explained mechanistically by Long’s work22. The short-lived intermediate triborane-9 (B3H9) is the only higher borane formed at moderate temperatures capable of splitting off hydrogen spontaneously. The resulting triborane-7 (B3H7) is also unstable and can react further with diborane to yield higher boranes, under elevated temperature conditions. However, as previously described, these were not observed under our milder operating conditions. Rather, it is likely that the triborane-7 disassociates into diborane and the non-volatile hydride of composition (BH)x, described by Long22, remaining in solution (depicted in Scheme 1). With diborane existing in equilibrium with 2BH3, it is easy to envision some of this material reforming the BTHF complex. This scenario is consistent with the results presented within this


10

Page 11 of 23

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


manuscript and provides a plausible explanation for the author’s failure to observe the appearance of higher boranes in the presence of significant hydrogen evolution. Scheme 1. Proposed Decomposition Mechanism for Diborane Leading to Higher Boranes and Hydrogen Evolution

Finally, a mass balance was performed on boron to determine whether or not we had accounted for all the boron in the system. Offline gas chromatography was used to identify and quantify the amount of tributoxyborane and dibutoxyborane that remained in solution. Reaction calorimetry was used to determine the amount of BTHF that remained after completing the 24 hour age at 55 °C, by destroying the remaining amount of BTHF with acetone and then comparing the heat evolved to that observed from the destruction of fresh BTHF (Table 1). The results, when combined, allowed us to perform a mass balance on boron. Looking at the results in Table 2, the amount of BTHF destroyed follows a similar pattern to results presented in Table 1, and that reactor fill appears to have an effect on the stability of BTHF in solution. Additionally, the boron mass balance24 was in very good agreement with theory, providing confidence in the BTHF decomposition component values listed in Table 1. Table 2. Calorimetry Results and Total Mass Balance Run 1 2 3

BTHF Destroyed (%)a 83.2 85.5 76.3

Boron Mass Balance (%)b 94.6 94.0 96.0


11


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

4 a

74.6

Page 12 of 23

99.1

b

Measured using RC1e. Total mass balance; Includes: total gas, dissolved species, and active BTHF remaining in solution

Risk Assessment of BTHF Processes. In assessing the risk of processes using 1 M BTHF, one must first consider the thermal stability of excess reagent present in the process25. Accelerating rate calorimeter (ARC) studies have shown that the reagent will undergo thermal decomposition, leading to runaway, at temperatures just above the solution boiling point. Further assessment, under isothermal aging conditions, has shown that the reagent can be held at 60 °C for a period of 12 hours and 55 °C for a period of 24 hours, without significant selfheating26. It is recommended that processes be run at temperatures

Process Safety Considerations for the Use of 1 M Borane

Recommend Documents