An Improved Do-It-Yourself Differential Scanning Calorimetry Glass

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An Improved Do-it-yourself Differential Scanning Calorimetry Glass Capillary Crucible for Thermal Safety Evaluation of a Chemical Process Sumio Shimizu, Tatsuo Ueki, and Makoto Takagi Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.7b00336 • Publication Date (Web): 18 Dec 2017 Downloaded from http://pubs.acs.org on December 19, 2017

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Organic Process Research & Development

An Improved Do-it-yourself Differential Scanning Calorimetry Glass Capillary Crucible for Thermal Safety Evaluation of a Chemical Process Sumio Shimizu*, Tatsuo Ueki and Makoto Takagi API R&D Center, CMC R&D Division, Shionogi & Co., Ltd., 1-3, Kuise Terajima 2-Chome, Amagasaki, Hyogo 660-0813, Japan

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ABSTRACT

We introduce a glass capillary crucible for DSC measurement that can be sealed by heating using an air-gas burner with cooling in an ice-water bath. The effect of the heating on the sample is minimal according to microscope photographs, DSC measurements and thermal transport calculations. The sealing operation does not cause significant distortion of the glass of the sealed crucible, which remains intact after the sealing operation. We developed an improved procedure for DSC measurement for this glass capillary crucible to enable its wider adoption for thermal safety evaluation of chemical processes.

KEYWORDS: DSC, glass capillary crucible, cooling in ice-water bath, low distortion, safety


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Introduction We previously proposed a do-it-yourself approach to differential scanning calorimetry measurement (DSC) using a glass capillary crucible, providing detailed information about the crucible and the holder, as well as the advantages of using this system.1 However, the approach required a liquid nitrogen bath for the cooling and an oxygen-gas burner for the glass capillary sealing. In addition to this, bursting of the sealed glass capillary crucible, cooled in a liquidnitrogen bath, could occur when it was returned to room temperature. In order to establish a better system, we focused on how to prevent the bursting of the crucible. This was hypothesized to occur due to distortion in the glass from the large temperature difference between heating and cooling. A 5-mm portion from the bottom end of the glass capillary is cooled by liquid nitrogen (-196˚C ) while a 2-mm upper portion above the liquid nitrogen is heated with an oxygen-gas burner (3000˚C)2. The maximum temperature difference can be as much as 3196˚C. If a liquid nitrogen bath is not used, the glass capillary can be sealed with a general air-gas burner (1300˚C)3 with cooling by dry ice (-76˚C) or ice (0˚C) which would not prevent combustion of the burner. This would reduce the maximum temperature difference to 1376-1300˚C．We tried preparing sealed glass capillaries more than 100 times under these conditions and found that the crucibles did not burst after the sealing operation. Moreover, we confirmed that by cooling in an ice-water bath, the sample substance for the DSC measurement was not significantly affected by the heat load. Here, we introduce an improved do-it-yourself approach to preparing samples for DSC measurements. When conducting DSC measurements, consideration of the inner surface of the crucible is very important for thermal safety evaluation, because when carrying out process


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safety testing on a 1-mg scale, the relative amount of surface exposed will be much greater than in the process vessels. Thus, for the process in a glass-lined reactor the ideal crucible would be one made of glass. Our improved method should allow the glass capillary crucible to be more widely used by manufacturing laboratories for thermal safety evaluation of a chemical process. Discussion Preparation of the glass capillary crucible by an improved glass capillary stand In our previous report, we introduced a glass capillary stand for sealing in a liquid nitrogen bath which consisted of a drill chuck and an aluminum pipe. However, it was difficult to stir the refrigerant with a stirring bar. We therefore developed a glass capillary stand consisting of a copper heat sink and an aluminum base which are connected by an M3 screw, with a space at the foot for a stirring bar (Figure 1). The orthographic drawing of the copper heat sink and the aluminum stand is shown in Figure 2. For the material of the heat sink, copper, which has better thermal conductivity than aluminum, was selected, and horizontal fins were attached to efficiently release heat from the burner to the stirred refrigerant. Because the roof of the heat sink has a tilt like a cupola in order to prevent the surface tension of water, the tilted roof of the heat sink can be submerged under water to a shallow degree to avoid direct exposure to the burner flame. All grooves of the heat sink are spread outward to allow the ice water to circulate easily. This heat sink is an improvement over the prototype heat sink with a flat head and flat grooves (Figure 3a).


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Figure 1a

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Figure 1b

Figure 1a. The improved glass capillary stand consists of a copper heat sink and an aluminum base. Figure 1b. A glass capillary cooled with the improved glass capillary stand in a stirred icewater bath.

Figure 2a. Orthographic drawing of the copper heat sink.


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Figure 2b. Orthographic drawing of the aluminum stand. For the DSC glass capillaries, capillaries for the Buchi melting point apparatus4 with a guaranteed clean interior are used. They are made from a glass capillary of 1.55 mm outer diameter tube, but have outside diameter variations depending on the end sealing operations. We prepared heat sinks with a hole with a diameter of 1.65 mm or 1.70 mm. The clearance gap between the hole and the capillary is filled by wrapping with copper or aluminum foil. The foil could be replaced by thermal grease for a computer processor. The test of inserting a glass capillary into a hole of diameter 1.65 mm was performed with 100 capillaries, with 37 glass capillaries being held in place without foil wrapping. Another 31 slender glass capillaries needed foil wrapping to hold them in place. As the remaining 32 thicker glass capillaries could not be inserted, a heat sink with a hole of the diameter 1.70 mm was needed. Wrapping of the glass capillary required practice. Hopefully, after the sealed crucible is removed from the heat sink and the wrapping foil is left behind in the hole of heat sink, then some following glass capillaries could be inserted without wrapping to the heat sink.


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Although we have used “do-it-yourself” in title, it is difficult to prepare the heat sink and entrusting it to a metalworking factory is recommended. Our first prototype glass capillary stand consisted of an aluminum pipe and an aluminum base, which has moderate cooling capacity (Figure 3b)．This can be prepared easily.

Figure 3a．．

Figure 3b．．

Figure 3a. The prototype glass capillary stand consists of a flat head copper heat sink and an aluminum base. Figure 3b. The prototype glass capillary stand consists of an aluminum pipe and an aluminum base. In the new method, the ice-water bath is fixed on a rotating swivel.1 To seal the glass capillary, the bath is rotated and the capillary is exposed to the burner flame from two or three directions to reduce heat distortion. Eliminating the need for liquid nitrogen reduces the risks involved in handling this refrigerant and makes it easier to obtain well-shaped crucibles. Thermal loading evaluation of the sample between tube sealing operations with ice-water cooling We chose tert-butoxycarbonylhydrazine (Boc-NHNH2) as a test sample, because it has a low melting point (41˚C) but non-hygroscopicity. The exposure to heat could be microscopically


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observed. A microscope photograph of the glass capillary crucible sealed with cooling in an icewater bath is shown in Figure 4. Comparison of the images from before and after the sealing clearly showed that almost all of the crystals in the glass capillary crucible had not melted in the sealing operation using an ice-water bath. The DSC results of Boc-NHNH2 in the glass capillary crucibles, which were cooled by liquid-nitrogen, dry ice, and ice-water are shown in Figure 5. There were no significant differences among them, showing that glass capillary crucibles for thermal safety evaluation of a chemical process can be sealed by cooling in an ice-water bath.5

Figure 4. Crystals of Boc-NHNH2 in the glass capillary: left, before sealing; right, after sealing.


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Figure 5. DSC comparison of Boc-NHNH2 for cooling refrigerants used: liquid nitrogen (black curve), dry ice (red curve), and ice water (blue curve). Another thermal loading evaluation was conducted using thermal transport calculations for the sealing operation of the glass capillary as shown in Figure 6.

First, total heat transport to the

sample in the glass capillary was estimated by the sum of heat conduction and heat of radiation through the glass capillary from the gas burner (1300˚C). Heat conduction from the gas burner through the glass capillary can be estimated by Eq. 16a, where D [˚C] is the temperature difference between the heating spot (1300˚C) and the top of the sample (25˚C), C [W/m K] is the coefficient of thermal conductivity of the glass capillary, A [m2] is the cross-sectional area of the glass capillary omitting the area of the hole, and B [m] is the distance between the heating spot


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and the top of the sample. When these values are assigned, E [W] heat transfer amount of the heat conduction is obtained as Eq. 2.

Figure 6. Sealing of the glass capillary by heating with gas burner and cooling in the heat sink．

E=××

(1)

where, A = 9.4 × 10 , B = 3.0 × 10 , C = 1.0W/m˚C, D = 1275 ˚C

!."×#$%& '( .$$×#$%) '

*

× 1.0 +˚, × 1275˚ = 0.40W

(2)

Heat radiation from a gas burner can be estimated by Eq. 36b, where S [m2] is the crosssectional area of the glass capillary, г is the emissivity of glass, T (˚C) is the heat temperature of the gas burner, T0 (˚C) is the sample temperature, and σ is Stefan's constant. When these values are assigned, E [W] heat transfer amount of the heat radiation is obtained as Eq. 4. E = S × r × σ0 + 273" − 0$ + 273"

(3)

where, S = 1.9 × 103 m , r = 1.0as worst case, T = 1300˚C, 0$ = 25˚C, σ＝ 5.7 × 10= W/ > "


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1.9 × 103 × 1 × 5.7e × 10= W/ > " 1300 + 273> " − 25 + 273> " = 0.66@ (4) For cooling, the heat transport to the sample in the glass capillary can be estimated as Eq. 56c where A [m] is the external radius of the glass capillary, B [m] is the internal radius of the glass capillary, C [W/m K] is the coefficient of thermal conductivity of the glass capillary, D [˚C] is the temperature difference between outer side and inner side of the glass capillary, and L [m] is the length of the glass capillary which is cooled in the heat sink. When these values are assigned, E [W] heat transfer amount of the cooling from a heat sink is obtained as Eq. 6.

E=

A×B×C×D

(5)

EF÷

where, D = 25K, A = 7.8 × 10" , J = 5.5 × 10" , = 1.0 W/mK, 5.0 × 10 m L×#.$*/+M×NM×N.$×#$%) + EF.=×#$%O '÷N.N×#$%O '

= 2.3@

K=

(6)

Because the cooling capacity of an ice-water bath (2.3W) exceeds the sum thermal migration of heat conduction (0.40 W) and heat radiation (0.66 W) from the gas burner heating, the cooling with stirring in an ice-water bath can remove the heat used to seal the glass capillary with a gas burner. DSC measurement using the glass capillary crucible. We have reported the advantages of a glass capillary crucible compared to a stainless steel (SS) crucible for metal-sensitive materials including acidic substances.1 Here we again show the advantage of the glass capillary crucible for DSC measurements of acidic substances. Since Vilsmeier reactions are useful for transformations of one-carbon homologation of electron-rich


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aromatic compounds,7 we report safety evaluations of the Vilsmeier reactions for scale up of the chemical process. Figure 7 presents DSC data of the Vilsmeier reagent prepared by the reaction of N,N-dimethylformamide (3.0 g: 42 mmol) with phosphorus oxychloride (4.2 g: 27 mmol) at 0˚C. The Vilsmeier reagent is acidic, has a chloride ion and easily reacts with metals. It must be prepared in a glass-lined reactor. We used the glass capillary crucible for safety evaluation of the chemical process. DSC data has revealed that the Vilsmeier reagent mixture has high decomposition heat and may be unstable at the process temperature in the glass-lined reactor.8 We therefore recommend in-situ preparation of the Vilsmeier reagent in the presence of the Vilsmeier reaction substrate.9

Figure 7. DSC data of the Vilsmeier reagent.


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Conclusion The glass capillary crucible can be sealed by cooling in an ice-water bath and heating with an air-gas burner. The obtained crucibles did not show excessive distortion during heating and quenching, and did not burst after the sealing operation. Of course, as a safety precaution the operator must wear goggles. Because the glass capillary used is inexpensive and the same material as a glass-lined reactor,10 the glass capillary crucible prepared by our method can be widely used for DSC measurements for thermal safety evaluation of chemical processes. Experimental section tert-Butoxycarbonylhydrazine, N,N-dimethylformamide and phosphorus oxychloride were purchased from commercial suppliers and used without further purification. The gas burner for sealing of the capillary was a compact blow torch PT 4000 : pen burner from Prince.3 DSC tests were performed on a Mettler Toledo HP 827e using Mettler STAR software. A digital microscope (Keyence, VHX 1000) was used to take the microscope photographs of the glass capillary at 50-fold magnification. General procedure of the preparation of the glass capillary crucible. Two capillaries for Buchi's melting point apparatus were cut to the suitable length, marked with a felt-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 each capillary. The walls of these glass capillaries were cleaned with a paper string to remove adhering sample. Alternatively, these capillaries were centrifuged (6000 rpm, 2 min) in a 15 mL polypropylene centrifuge tube to clean the walls. The two filled capillaries were reweighed using


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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 an ice-water bath. The marked position was heated by flame and the capillary was sealed. The glass capillary crucible with the more appropriate shape was chosen, wrapped in aluminum foil and used for the DSC measurement at a scan rate of 10˚C/min under 3 Mpa with a nitrogen purge gas flow at 50 mL/min. Acknowledgment We thank Mr. Y. Takeuchi, Dr. K. Nishi, Dr. N. Kurose, Dr. Y. Murata, 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. K. Kawashita, Engineering Technology Department, Shionogi & Co., Ltd., for their support during the preparation of the copper heat sink and the aluminum base. Author Information Corresponding Author E-mail: [email protected] ORCID Sumio Shimizu: 0000-0001-8695-6350 Notes The authors declare no competing financial interest.

References


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1) Shimizu, S.; Ueki, T., Org. Process Res. Dev., 2017, 21, 304. 2) http://www.shinfuji.co.jp/sfb/products/ot-3000/ (in Japanese) 3) http://www.prince-lighter.com/torch/ 4) Melting Point M-560 : https://www.buchi.com/us-en/products/melting-point/melting-point-m560 5) Decrease of about 30 % of decomposition heat was observed in the measurement of the liquidnitrogen cooling sample (black curve) compared with the dry ice cooling sample (blue curve). The cause about this difference may be regarded as moisture，oxygen and non-uniform sample etc., but it isn't clear. We recommend that the measurement for a high-risk process should be more than one time in order to check the reproducibility. In this regard, we have checked the reproducibility of this glass capillary method by 3 times measurements of standard samples (Indium : 6.259mg, 6.114mg and 6.286mg). These onset temperatures and melting heats were 156.60˚C, 156.80˚C, 157.08˚C and 28.31J/g, 28.29J/g, 28.25J/g respectively. 6) (a)Bird, R.B.; Stewart, W.E.; Lightfoot, E.N.; Transport Phenomena, John Wiley & Sons, New York, 1960, P244., (b) ibid., P444., (c) ibid., P278. 7) (a) Vilsmeier, A.; Haack, A., Ber.,1927, 60, 119., (b) Meth-Cohn, O.; Stanforth, S. P., Comprehensive Organic Synthesis, Pergamon, Oxford, 1991, 2, p777., (c) Jones, G.; Stanforth, S. P., Organic Reactions, John Wiley & Sons, New York,1997,49,p1.


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8) Thermal hazard evaluations of Vilsmeier reagent have been reported as follows. (a) Miyake, A.; Suzuki, M.; Sumino, M.; Iizuka, Y.; Ogawa, T., Org. Process Res. Dev., 2002, 6, 922., (b) Bollyn, M., Org. Process Res. Dev., 2005, 9, 982. 9) Although DSC is the most common screening test for thermal safety evaluation of a chemical process, a pressure data is lacking from DSC analysis. A correct judgment of the process safety evaluation needs more accurate data about heat and pressure from Accelerating rate calorimeter (ARC) as a typical. For example. a) S. M. Rowe, Org. Proccess Res. Dev. 2002, 6,877., b) D. J. Dale, Org. Proccess Res. Dev. 2002, 6,933., c) G.T. Bodman,; S. Chervin, J. Hazard. Mater. 2004,115,101. 10) In a precise sense, the glass capillary is made from soda-lime glass, and not same glass material as inner surfaces of glass-lined reactors which have high chemical resistance. Soda-lime glass may be the worst material about chemical resistance among glass materials. However, because soda-lime glass is readily melt-processable and considerably chemically stable, the sodalime glass capillary is good for our glass capillary crucible.


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An Improved Do-It-Yourself Differential Scanning Calorimetry Glass

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