Do-It-Yourself: Differential Scanning Calorimetry Glass Capillary

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Do-It-Yourself: Differential Scanning Calorimetry Glass Capillary Crucible for Thermal Safety Evaluation of a Chemical Process Sumio Shimizu* and Tatsuo Ueki API R&D Center, CMC R&D Division, Shionogi & Co., Ltd., 1-3, Kuise Terajima 2-Chome, Amagasaki, Hyogo 660-0813, Japan S Supporting Information *

ABSTRACT: In 1988, Whiting et al. reported the first differential scanning calorimetry measurement in a glass capillary crucible, providing general information about the crucible and the holder as well as the advantages of using this system. However, the glass capillary crucible and the holder are not yet commercially available. Here we introduce a glass capillary crucible developed with our know-how to encourage its wider adoption in order to reduce costs by obviating the need for commercial gold-plated crucibles. KEYWORDS: differential scanning calorimetry, glass capillary crucible, thermal safety evaluation, do-it-yourself, cost reduction

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INTRODUCTION At the start of thermal safety evaluation of a chemical process, differential scanning calorimetry (DSC) is used for screening to estimate the comprehensive thermal stabilities of raw materials, products, intermediates, reagents, reaction mixtures, and concentrated mixtures in the chemical process.1 From about 1 mg of sample, DSC can provide important data on the decomposition onset temperature, the heat, and its flow. Confirmation of thermal safety can be completed without additional measurements using other calorimeters if the decomposition onset temperature is relatively high and the heat level is relatively small.2 Consideration of the inner surface of the crucible used for DSC measurements is very important for thermal safety evaluation, because when carrying out process safety testing on a 1 mg scale, the relative amount of surface exposed will be much greater than in process vessels. As a general rule, a goldplated DSC crucible, with excellent chemical resistance, has been recommended for process safety testing.3 However, a recent scanning electron microscope study revealed that goldplated surfaces of commercially supplied DSC crucibles contain pinholes which cause samples to easily come into contact with the underlying copper or nickel.4 Therefore, in the Japanese Industrial Standards, a high-pressure low-carbon stainless steel (SS) crucible has been recommended to measure exothermic decomposition energy for estimation of explosiveness. We switched from a gold-plated crucible to a SS crucible for screening of thermal safety evaluation. However, because acidic substances react with the internal surface of a SS crucible, it is not suitable for their thermal analysis. For the safety evaluation of substances which are treated in a glass-lined vessel, the most desirable crucible would be made of glass. Glass ampules have been marketed as glass pressure crucibles5 but are presently difficult to acquire. As part of our ongoing efforts to study thermal analysis for safety evaluation of chemical processes,6 we decided to establish a procedure of DSC measurement using a glass capillary crucible, as reported by Whiting et al.7 As the glass capillary crucible and the holder are not available commercially,8 we went through time© 2017 American Chemical Society

consuming endeavors for successful DSC measurement. This enabled us to achieve an appreciable cost reduction in comparison with a process using a gold-plated DSC crucible. Here we report what we learned during the process of developing the glass capillary crucible and the DSC measurement. This information should be useful for those wishing to try DSC measurement using a glass capillary crucible, which advantageous for DSC measurement of metal-sensitive materials including acidic substances.

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DISCUSSION Preparation of the Glass Capillary Crucible. A capillary for the Buchi melting point apparatus with a guaranteed clean interior was used as a DSC glass capillary. It is inexpensive and can help reduce running cost for screening of process safety when compared with the use of a gold-plated DSC crucible. The capillary has an inner diameter of 1.1 mm, an outer diameter of 1.55 mm, and a length of ca. 80 mm. The glass capillary is quite narrow and can fit a sample of ca. 1 mg in the closed end. We recommend cutting it short to suit the use. In case of a solid sample, the open end of the capillary is pressed over the sample, which has been sprinkled on a piece of weighing paper, and then the capillary is turned over to allow the sample to enter the closed end by repeatedly tapping the capillary against a hard surface. For a liquid sample, a micro syringe should be used to inject the sample, the quantity of which can be adjusted easily by the amount taken up into the syringe. A Pasteur pipet with a diameter small enough to insert into the glass capillary can also be used. By expanding air in the pipet with hand-warming, the desired amount of sample can be introduced into the glass capillary. One important point is to prevent the sample from adhering to the interior surface. This could cause a weighing error. Moreover, when melting and sealing the glass capillary with a burner, the pyrolyzed material of the adhering sample can contaminate the sample. We recommend cleaning by passing a Received: October 20, 2016 Published: January 31, 2017 304

DOI: 10.1021/acs.oprd.6b00350 Org. Process Res. Dev. 2017, 21, 304−309

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Figure 1. Indium, NBS, and 50% hydroxylamine in glass capillary crucibles.

Figure 2. Bath with a rotating swivel and capillary stand.

Figure 3. Sealing of the glass capillary in a liquid-nitrogen bath on capillary stand.

Figure 4. Cooling with dry ice using an aluminum foil holder.

twisted paper string made from Kimwipes disposable wipers through the capillary to remove any adhering sample. The injected sample in the glass capillary is cooled in a liquid nitrogen bath, and then the open side of the capillary tube is sealed by melting using a gas burner. The result is a sealed crucible about 8 to 9 mm long like a rice grain (Figure 1). This procedure requires careful attention to the following points: 1. The sealed crucible, which is thicker than the original diameter of the capillary, cannot be inserted into the holder. It is therefore necessary to seal the glass capillary keeping it in a straight form without thickening. In general glass-working, a glass tube to be sealed is rotated for uniform heating. When it softens and is removed from the flame, it lengthens and constricts to about half its original diameter. The constricted area of the glass tube is then placed in the flame again to melt it

for sealing. However, as the glass capillary has to be cooled in a liquid-nitrogen bath, it cannot be rotated using both hands. Although rotating the glass capillary would probably be ideal, as it is thinner than the flame, it should be possible to seal it by rotating it. Thus, the liquid-nitrogen bath is fixed on a rotating swivel (Figure 2). To seal the glass capillary, the flame hits it from two or three directions as the liquid-nitrogen bath is rotated. The heating from different directions contributes to sealing the tube in a good shape and reducing heat distortion (Figure 3). 2. Next, the glass capillary needs to be easily fixed in the liquid-nitrogen bath, and the sealed capillary crucible should be easy to remove. We recommend using a stand consisting of an aluminum tube and a drill chuck.9 The top end of the 305

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When the glass capillary crucible wrapped in aluminum foil was inserted into the hole of the holder, the heat from the sample is transmitted to the DSC sensor with less heat loss than when the naked glass capillary crucible is inserted directly (Figure 7). DSC Measurements Using the Glass Capillary Crucible. We used high-pressure DSC for measurement under atmospheric pressure or high pressure (3−5 MPa) with a nitrogen purge gas flow at 40−50 mL/min. Pressurization using nitrogen around the glass capillary crucible seems to help prevent breaking of the glass crucible. In many cases, however, measurement under atmospheric pressure is possible. Even if the glass crucible is destroyed, because glass splinters would be released only from both apertures of the holder, a break of the DSC sensor may be prevented. The glass capillary crucible was calibrated using about 6 mg of indium before sample measurement. This calibration was based on measuring the onset temperature (156.6 ± 0.3 °C) of fusion and the heat of fusion of indium (28.45 ± 0.60 J/g) within the tolerance limits defined by Mettler Toledo. Iwata and Koseki have reported that thermal decomposition of 50% hydroxylamine aqueous solution was remarkably accelerated due to a catalytic effect of the stainless steel surface of a SS crucible, based on comparative differential thermal analysis (DTA) measurements between a gold-plated crucible and a SS crucible.10 The decomposition onset temperatures were observed at about 75 °C for the SS crucible and about 130 °C for the gold-plated crucible. We carried out the same comparative DSC measurements for the SS crucible and the glass capillary crucible.11 The results for 50% hydroxylamine aqueous solution are shown in Figure 8. The decomposition onset temperature in the glass capillary crucible was observed at 208 °C, which is 158 °C higher than in the SS crucible. As these 50% hydroxylamine aqueous solutions were subjected to measurements with different instruments (DTA and DSC) and their production lots were different, the obtained results may not be compared directly, but the decomposition onset temperatures may be ranked as follows: SS crucible ≪ goldplated crucible < glass capillary crucible. This shows that a glass capillary crucible has excellent chemical resistance. As the decomposition of hydrogen peroxide is known to be promoted by various metal catalysts,12 we conducted DSC measurements of a 30% hydrogen peroxide solution in both crucibles to check for an influence of SS. Decomposition in the SS crucible began at an onset temperature of 68 °C with a decomposition heat of 951 J/g, while in the glass capillary crucible, the onset temperature was 153 °C with a decomposition heat of 992 J/g (Figure 9). The difference of these onset temperatures indicates that the SS surface acts as a catalyst in the decomposition of hydrogen peroxide, suggesting that a glass-lined vessel is better suited for treatment of 30% hydrogen peroxide solution and that more attention needs to be paid to preventing metal contamination, for example, glasslining integrity check. Hydroxylamine hydrochloride and methylated hydroxylamine hydrochlorides were also measured in both types of crucible, and the results are shown in Figure 10. Hydroxylamine hydrochloride11 and O-methylhydroxylamine hydrochloride decomposed without melting in the SS crucible, but in the glass capillary crucible, the melting and the decomposition could be distinctly observed. In the SS crucible, Nmethylhydroxylamine hydrochloride and N,O-dimethylhydroxylamine hydrochloride melted and simultaneously decomposed,

aluminum tube is divided into three sections to allow easy grasping of the glass capillary (Figures 2 and 3). 3. The flame heat should not be allowed to affect the sample in the glass capillary. Thus, a minimal area of the glass capillary should be fused while cooling in a liquid-nitrogen bath. We recommend a miniature oxygen-gas burner with a small nozzle (0.5 mm in diameter) emitting a flame that does not disappear in a nitrogen atmosphere. 4. Cooling can be done by liquid nitrogen, dry ice, or ice, according to the nature of the sample. When using a solvent with dry ice or ice, an incombustible solvent or no solvent should be used (Figure 4). 5. When a glass capillary crucible sealed under cooling with liquid nitrogen returns to room temperature, the pressure inside will be more than 3 atm. Therefore, a glass capillary crucible occasionally bursts due to some distortions in the glass accrued during heating and quenching (Figure 5). The operator must wear goggles, and the sealed capillary must be stored in a small plastic bag as soon as it returns to room temperature to prevent flying debris if it bursts.

Figure 5. Burst glass capillary crucible in a small plastic bag.

Preparation of the Glass Capillary Crucible Holder. The sealed glass capillary crucible cannot be loaded directly into the DSC. Whiting et al.7 recommends using a holder. We recommend a holder made from an aluminum rod (8.0 mm in diameter) that can be purchased at do-it-yourself stores. The orthographic drawing of the holder is shown in Figure 6. The

Figure 6. Orthographic drawing of the holder.

base should be flat to transmit heat from the holder into the sensor of the DSC with minimum heat loss. We recommend polishing the base with waterproof abrasive paper. The upper part is shaped like a roof to reduce the thermal capacity of the holder and raise the sensitivity of the DSC measurement. Holders for the sample and the reference should be of the same mass; this can be achieved by rasping off the upper parts (Figure 7). 306

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Figure 7. Holder and a glass capillary crucible wrapped in aluminum foil.

materials and that glass-lined vessels are more suitable when dealing with such compounds. 4-Chlorobenzyl chloride, 2-nitrobenzenesulfonyl chloride, and 3-chloroperbenzoic acid (MCPBA) were also measured using both types of crucible. In the SS crucible, 4-chlorobenzyl chloride decomposed at an onset temperature of 150 °C with decomposition heat of 151 J/g, but in the glass capillary crucible, it did not decompose until 300 °C (Figure 11). The Figure 8. 50% Hydroxylamine solution: DSC comparison between a high-pressure SS crucible (black curve) and a glass capillary crucible (red curve).

Figure 11. 4-Chlorobenzyl chloride: DSC comparison between a highpressure SS crucible (black curve) and a glass capillary crucible (red line).

Figure 9. 30% Hydrogen peroxide solution: DSC comparison between a high-pressure SS crucible (black curve) and a glass capillary crucible (red curve).

obvious difference was verified by a DSC measurement in a reusable PerkinElmer SS high-pressure crucible which can check the sample after the measurement.13 The sample turns into a gel after the measurement. This was extracted with chloroform-d1, measured by 1H NMR, and broad multiplet peaks for aromatic and benzyl protons are observed. Furthermore, the SS crucible was washed with detergent, water, and sonication; therefore, corrosive damages and a −0.105 mg loss in weight are observed. This result obviously indicates that 4-chlorobenzyl chloride thermally reacts with SS. In contrast, the glass capillary sample becomes a bit yellow only; singlet peaks for 4-chlorobenzyl chloride are observed in the 1H NMR spectra.13 When the decomposition heat is observed by a reaction between a sample and SS, the measurement using an SS crucible overestimates the risk associated with the heat but reveals the risk associated with metallic contamination. Almost the same melting points of 2nitrobenzenesulfonyl chloride were observed in both crucibles, and the decomposition events were observed sometime after the melting (Figure 12). The decomposition onset temperature in the glass capillary crucible was observed from a temperature 84 °C higher than in the SS crucible. In both types of crucible, MCPBA melted at the same temperature before decomposition. The peak temperature of decomposition in the glass capillary crucible was observed at a temperature 50 °C higher than in the SS crucible, and the peak was a gentle curve (Figure 13).

Figure 10. Hydroxylamine hydrochloride and methylated hydroxylamine hydrochlorides: DSC comparison between a high-pressure SS crucible (black curve) and a glass capillary crucible (red curve).

while in the glass capillary crucible, they decomposed sometime after melting. In the glass capillary crucible, a distinct separation between the melting and the decomposition was observed. These findings show that glass materials have less impact on the thermal decomposition of these hydrochlorides than SS 307

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tipped marker pen in order to be distinguishable from each other, and then weighed with a microbalance using microgram weights. A sample of ca. 1 mg was put into the closed end of five capillaries. The walls of these glass capillaries were cleaned with a paper string to remove the adhering sample. The five filled capillaries were reweighed using the microgram weights in order to accurately weigh the samples. These capillaries were marked with a felt-tipped marker pen at ca. 7 mm from the closed end and cooled on a capillary stand in a liquid-nitrogen bath. The marked position was heated by flame, and the capillary was sealed. The glass capillary crucible with the most appropriate shape was chosen from these five and used for the DSC measurement at a scan rate of 10 °C/min.

Figure 12. 2-Nitrobenzenesulfonyl chloride: DSC comparison between a high-pressure SS crucible (black curve) and a glass capillary crucible (red curve).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.oprd.6b00350. DSC experiment results of 4-chlorobenzyl chloride by a reusable PerkinElmer SS high-pressure crucible and a glass capillary crucible (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected].

Figure 13. MCPBA: DSC comparison between a high-pressure SS crucible (black curve) and a glass capillary crucible (red curve).

ORCID

Sumio Shimizu: 0000-0001-8695-6350 All results clearly show that a glass-lining vessel is suitable for handling of these acidic substances and metal sensitive materials, and the glass capillary crucible for thermal safety evaluations of chemical process should be used.

Funding

CONCLUSION For the thermal safety evaluation of a substance which is treated in a reactor, the most desirable inner surface of the DSC crucible would be of the same material as the reactor. A glass capillary crucible is suitable for DSC measurement of acidic substances, metal-sensitive materials, and hydrochlorides which are treated in glass-lined vessels. For DSC screening tests, using a glass capillary crucible can lead to a great cost reduction compared with the use of a gold-plated DSC crucible. Glass capillary crucibles should be more widely used for DSC measurements.

Notes

All research funding sources for all authors were provided by Shionogi & Co., Ltd., CMC R&D Division, Amagasaki, Hyogo, 660-0813, Japan.

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The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank Mr. Y. Takeuchi, Dr. N. Tanimoto, Dr. T. Yasukata, Dr. K. Nishi, Dr. M. Iguchi, and Mr. K. Ban, API R&D Center, CMC R&D Division, Shionogi & Co., Ltd., for their encouragement and support during this work. We also thank Mr. M. Ishikawa, Mr. H. Nakajima, and Mr. K. Kawashita, Engineering Technology Department, Shionogi & Co., Ltd., for their support during the preparation of the glass capillary holder and the stand. Furthermore, we thank the editor-inchief, anonymous reviewers, and Mr. I. Priestley, Huddersfield Manufacturing Centre, Syngenta Ltd., for their constructive suggestions.

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EXPERIMENTAL SECTION N-Methylhydoxylamine hydrochloride, O-methylhydoxylamine hydrochloride, and N,O-dimethylhydoxyamine hydrochloride were purified by recrystallization from a mixture of AcOEt and MeOH. Other materials were purchased from commercial suppliers and used without further purification. The gas burner for sealing of the capillary was a compact caster type oxygen welding burner O2 torch OT-3000 from New-Fuji.14 DSC tests were performed on a Mettler Toledo HP 827e using Mettler STAR software. High-pressure SS crucibles were Shimazu pressure-proof stainless steel 304 hermetic pans (limit pressure: 5 MPa). These were washed with acetone and preheated at 500 °C under N2 before the DSC measurements at a scan rate of 10 °C/min. General Procedures of the Preparation of the Glass Capillary Crucible. Five capillaries for Buchi’s melting point apparatus were cut to the suitable length, marked with a felt-

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REFERENCES

(1) (a) Frurip, D. J.; Elwell, T. Process Saf. Prog. 2007, 26, 51. (b) Frurip, D. J. Org. Process Res. Dev. 2008, 12, 1287. (2) (a) Stoessel, F. Thermal Safety of Chemical Processes: Risk Assessment and Process Design; Wiley-VCH: Weinheim, 2008; p 286. Stoessel described the onset determined using the DSC’s software by a tangential method is a concept without scientific basis. In the field of chemical reaction hazard assessment, it is more rigorous to consider the exotherm detection threshold as when the rate of heat generation exceeds 10 W/kg (0.01 W/g). (b) Keller, A.; Stark, D.; Fierz, H.; Heinzle, E.; Hungerbuhler, H. J. Loss Prev. Process Ind. 1997, 10, 31. (c) Rowe, S. M. Org. Process Res. Dev. 2002, 6, 877. (3) Stoessel, F. Thermal Safety of Chemical Processes: Risk Assessment and Process Design; Wiley-VCH: Weinheim, 2008; p 92.

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(4) (a) Akiyoshi, M.; Sasakibara, T.; Okada, K.; Usuba, S.; Matsunaga, T.; Okuda, A. Presented at The 44th National Conference of Japan Society for Safety Engineering, Yonezawa, Yamagata, Dec 2011. (b) Japanese Industrial Standard: Measurement method of exothermic decomposition energy for explosive estimation, JIS K 4834; Japanese Standards Association: Tokyo, 2013, 18 (in Japanese). (5) TA Instruments had been selling 'DSC Glass Ampoule Sealer' as a glass capillary preparation system in the past. (6) Shimizu, S.; Imamura, Y.; Ueki, T. Org. Process Res. Dev. 2014, 18, 354. (7) (a) Whiting, L. F.; Labean, M. S.; Eadie, S. S. Thermochim. Acta 1988, 136, 231. (b) Taylor, G. R.; Dunn, G. E.; Easterbrook, W. B. Anal. Chim. Acta 1971, 53, 452. (c) Tou, J. C.; Whiting, L. F. Thermochim. Acta 1980, 42, 21. (8) Although rarely used, flat bottom crucibles prepared from glass are commercially available, but are expensive and are not the capillaries that we describe. (9) Akiyoshi, M.. Presented at the 26th workshop of Process Safety Study Group of Environment & Safety Committee of The Japan Pharmaceutical Manufacturers Association, Tukuba, Ibaraki, Jun 2013. Akiyoshi showed that a glass capillary was fixed by a drill chuck in a liquid-nitrogen bath. (10) Iwata, Y.; Koseki, H. Process Saf. Prog. 2002, 21, 136. (11) (a) The same experiments have been reported: Safety Guide of The National Institute of Industrial Safety, Guide for Explosion Hazards of Hydroxylamines and Their Safe Handling, NIIS-SG-NO. 1, 2001 (in Japanese). (b) The remarkable influence of crucible material on the observed DSC's has been described in a conference report: Arthur, G. S.; Williams, C. The effect of Crucible type on differential scanning calorimetry (DSC) measurements. IChemE Symposium Series No 150, 2004; p 1−11. (12) Bretherick’s Handbook of Reactive Chemical Hazards, 7th ed.; Urben, P. G., Ed.; Elsevier: Amsterdam, 2007; p 1705. (13) DSC curves, 1H NMR spectra, and pictures of both crucibles are showed in Supporting Information. (14) http://www.shinfuji.co.jp/sfb/products/ot-3000/ (in Japanese).

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