Scale-Up Synthesis of Hexabenzylhexaazaisowurtzitane, an

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Scale-Up Synthesis of Hexabenzylhexaazaisowurtzitane, an Intermediate in CL-20 Synthesis Tomasz Gołofit,*,† Paweł Maksimowski,† Piotr Szwarc,‡ Tomasz Cegłowski,‡ and Joanna Jefimczyk† †

Faculty of Chemistry, Division of High Energetic Materials, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland ‡ Chemical Works “NITRO−CHEM” S.A., Wojska Polskiego 65 A, 85−825 Bydgoszcz, Poland S Supporting Information *

ABSTRACT: After successful synthesis of hexabenzylhexaazaisowurtzitane (HBIW) on a laboratory scale (0.25 L reactor), it was performed on a multilaboratory scale (10 L reactor) and subsequently in an experimental installation in which a 300 L reactor was built. Seven syntheses were carried out in the unit on a pilot scale to produce 250 kg of HBIW. The pilot-scale syntheses ran with a yield comparable to those observed for the processes conducted on a large-laboratory scale. Some modifications were suggested that allowed for reduction of the HBIW weight unit by approximately 50%.

1. INTRODUCTION The synthesis of 2,4,6,8,10,12-hexabenzyl-2,4,6,8,10,12hexaazatetracyclo[5.5.0.05,9.03,11]-dodecane (HBIW) is the first stage in the production of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12hexaazatetracyclo[5.5.0.05,9.03,11] dodecane (CL-20), which is the most potent explosive known today. Because of the high performance characteristics of CL-20, a number of research projects are being conducted worldwide on CL-20 synthesis, properties and applications.1−4 HBIW is formed as a result of condensation of three glyoxal molecules with six benzylamine molecules. The reactions are conducted in organic solvents in the presence of catalysts, which are protonic acids such as chloric(VII), sulfuric(VI), or formic acids. The yield of the synthesis depends on many parameters, such as reaction temperature and duration, concentration and dosing rates of substrates, solvent type, as well as catalyst type and amount. The proposed mechanism of HBIW formation involves multiple stages.5 Two of the intermediate products are dicarbinolamine and diimine. The detailed mechanism of HBIW formation is given in the Supporting Information. Acetonitrile is commonly mentioned in the literature as a solvent in this reaction.5−11 Little information could be found regarding HBIW synthesis in methanol. The results of the studies carried out by our research group on HBIW synthesis on a laboratory scale allowed us to select methanol as a preferred solvent for the commercial HBIW manufacturing process along with chloric(VII) acid, HClO4, or sulfuric(VI) acid, H2SO4, as the catalyst.12,13 The highest yield of the synthesis was achieved with chloric (VII) acid.12 Replacement of acetonitrile (ACN) with methanol will reduce the production cost of HBIW. The price of MeOH is approximately $0.3 USD/kg, whereas the ACN price amounts to $3.0 USD/kg. Methanol is therefore approximately 10-fold less expensive as compared to that of acetonitrile. Another advantage of methanol is its lower toxicity than that of ACN. The maximum momentary allowable concentration for methanol is equal to 300 mg/m3, whereas for acetonitrile it is 140 mg/m3. © XXXX American Chemical Society

The purpose of this work was to carry out HBIW synthesis on a pilot-plant scale and to obtain the intermediate that would allow us to produce CL-20 in several-kilogram-sized quantities. Additionally, the effect of deviation of the process parameters on the yield of the reaction conducted on a pilot scale was examined. Results of these experiments may serve as a basis for the determination of analogous parameters for the target manufacturing scale.

2. EXPERIMENTAL SECTION 2.1. Materials. Benzylamine (BASF), benzylamine content >99% as determined by GC; glyoxal (BASF as aqueous solution; glyoxal content, 39.5−40.5% (as determined by BASF method; methanol (Brenntag, Polska Sp. z o. o.); methanol content >99.85% by GC; chloric(VII) acid (CHEMITEST warehouse), chloric(VII) acid content, 60%; and sodium carbonate (CIECH S.A.) technical grade. 2.2. Analysis of Purity. HPLC Analysis. HPLC analyses were carried out with a Shimadzu LC-10AD chromatograph equipped with a TSK Si-150 column, 4.6 × 250 mm, 5 μL of the analyzed sample injection. A chloroform/acetonitrile mixture was applied as the eluent with the volume ratio of 90:10 and a flow rate of 1 mL/min. A UV SPD-10A detector was used, and chromatograms were recorded at a wavelength of 254 nm. Samples for analysis were prepared as follows: approximately 20 mg of the analyzed substance was dissolved in 5 mL of acetonitrile, and the resulting solution was filtered and dosed into the chromatographic column. The retention time for HBIW was 7.1 min. Prior to testing, all substances were dried to a constant weight at 60 °C. Because of the high reactivity of intermediate products, HPLC analysis was performed immediately after preparation of the solution. DSC Analysis. Measurements were made on a heat-flux DSC 605 UNIPAN calorimeter. The calibration was performed with gallium, indium, cadmium, tin, zinc naphthalene, and benzoic Received: March 16, 2017 Published: June 2, 2017 A

DOI: 10.1021/acs.oprd.7b00101 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

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high reactivities, which is why the differential scanning calorimetry-cryometric method17−19 was chosen to perform further studies. Assumptions for the cryometric method are presented in the Supporting Information. This method can be used to determine the total content of impurities. Although it does not allow for identification of the impurities, it has many advantages such as short analysis time, no solvent, as well as no need for anhydrous conditions. 3.1. HBIW Synthesis on a Large Laboratory Scale. The first stage of research consisted of increasing the synthesis scale from 0.25 to 10 L. The synthesis was performed in accordance with the description in section 2.3. DSC analyses were performed to determine the purity of thus-obtained HBIW samples. Studies on the purification process were described in an earlier paper.20 Figure 1 shows an example of the results of these analyses.

acid. Purity values of the metals used were above 99.999%. Purity values of organic substances used were higher than 99.95%. Measurements were performed using hermetic aluminum pans in which the samples were sealed under reduced pressure of approximately 1.3 kPa. The samples were heated to 170 °C with a heating rate of 2 K min−1. 2.3. HBIW Synthesis and Purification. Large-laboratory scale synthesis was performed in a 10 L reactor equipped with a reflux condenser, thermocouple, mechanic stirrer, and a heating−cooling jacket. The following reagents were poured into the reactor: methanol (5.00 L), water (0.44 L), benzylamine (1.30 L, 11.8 mol), and 60% chloric(VII) acid (0.15 L, 1.4 mol). While stirring, the reaction mixture was cooled to 5 °C. Then, a 40% aqueous glyoxal solution (0.60 L, 5.3 mol) was introduced into the reactor using a peristaltic pump over 2 h. The vessel content was maintained at 50 °C for 4 h. Next, the reaction mixture was cooled to 20 °C and then filtered. The precipitate was washed with 4.00 L of methanol. Upon drying, a total of 911 g of HBIW was obtained with mp 146−150 °C, cryometric purity of 92.8 mol %, and yield of 68%. After methanol (5.00 L) was poured into the reactor, crude HBIW (500 g, 0.71 mol) and aqueous sodium carbonate (10 g, 94 mmol) in 50 mL water solution were added. The whole volume was vigorously stirred at the methanol boiling temperature for 30 min. Subsequently, the suspension was filtered. The precipitate was washed with ∼1.50 L of methanol and transferred into the reactor for another purification stage. Subsequently, 5.00 L of methanol was poured into the reactor, and the mixture was heated to the boiling point under vigorous stirring. After 30 min, HBIW was filtered off, and the precipitate was washed with 1.00 L of methanol. Upon drying, 432 g of pure HBIW (0.61 mol) was obtained. The purified HBIW was white and melted at 152−155 °C; the purity, as determined cryometrically, was equal to 96.0 mol %. The yield of the purification process in terms of crude HBIW was 89%. FTIR υ (cm−1): 3022, 2835, 1954, 1669, 1602, 1492, 1451, 1396, 1351, 1302, 1264, 1208, 1169, 1140, 1122, 1072, 1057, 1028, 1017, 986, 926, 896, 828, 792, 781, 749, 732, 698. 1H NMR (CDCl3, 400 MHz): δ 7.39−7.42 (m, 30 H, phenyl CH), 4.33 (s, 4 H, CH2), 4.26−4.27 (d, 8 H, CH2), 4.21 (s, 4 H, CH), 3.75 (s, 2, H, CH). Pilot scale synthesis was performed in an analogous way to that of the large-laboratory scale synthesis.

Figure 1. DSC curves of the HBIW melting process in samples before and after purification.

HBIW was obtained with a cryometric purity of 92.8 mol % and 73% yield. The reaction yield here was comparable with the value for the analogous reactions conducted for a smaller-scale. The sample purity increased to 96.0 mol % after the purification. The yield of the purification process was 89%. Attention was also paid to the question as to how the deviations of the values of major parameters would affect the ultimate HBIW yield, including the effects of deviations of such parameters as temperature, reaction time, amount of catalyst used, glyoxal addition temperature, and reactant concentration. The attained results are listed in Table 1. Analysis of the melting temperature was used for estimation of the sample purity; a higher sample purity resulted from higher melting temperature, e.g., a melting temperature of 146−150 °C resulted in a sample purity of 92.8 mol % and 152−155 °C resulted in 96.0 mol %. The first parameter modified was the reaction time. Extension of the reaction time from 4 to 16 h resulted in a reduced reaction yield and a lower product purity. Likewise, reduction of the reaction time to 2 h resulted in a diminished product yield and inferior purity. Raising the reaction temperature to 60 °C has an unfavorable effect on the process: a drop in HBIW yield and purity were observed. A lower glyoxal addition temperature has virtually no effect on the reaction yield, although it increases the purity of the obtained HBIW. In contrast, an increase in the glyoxal addition temperature above 15 °C reduces both the product

3. RESULTS AND DISCUSSION The following substances are impurities of HBIW: 2,4,6,8tetrabenzyl-2,4,6,8-tetraazabicyclo[3.3.0]octane, dicarbinolamine, diimine, as well as products of their condensation with high molecular mass.14 Contaminations of substrates, such as 2-aminebenzylamine and formaldehyde, will cause contamination of HBIW with 2,4,6,8-tetrabenzyl-2,4,6,8tetraazabicyclo[3.3.0]octane15 and 2,2′-bi(1,2,3,4-tetrahydroguanasoline),16 which is why contaminated substrates and solvents should not be used for synthesis. HPLC analyses of HBIW were performed. Diimine is the main impurity of HBIW synthesized using methanol. Dicarbinolamine and two other unidentified compounds were also detected. HPLC analysis allowed the qualitative determination of impurities, but it requires the use of anhydrous conditions, and measurements should be carried out immediately after the preparation of the solutions. Dicarbinolamine and diimine cannot be quantified with this method due to their B

DOI: 10.1021/acs.oprd.7b00101 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

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Table 1. Effect of Reaction Conditions on the Reaction Yield and the HBIW Melting Point no.

nHClO4/ nBnNH2a

glyoxal adding temp [°C]

reaction temp [°C]

reaction time [h]

yield of crude HBIW [%]

melting point [°C]

1 2 3 4 5 6 7 8 9

0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.3

15 15 15 15 50 0 15 15 15

50 50 50 60 50 50 35 35 35

2 4 16 4 4 4 16 16 16

61. 5 73.1 65.0 57.3 47.5 72.7 68.8 75.0 80.6

144−147 149−153 147−150 143−146 135−137 151−153 151−153 135−143 126−140

a

Molar ratio of chloric(VII) acid to benzylamine.

yield and purity. A decrease in the reaction temperature from 50 to 35 °C results in a minor increase in the yield and purity of the HBIW obtained after 16 h. To increase the reaction yield at a reduced temperature, the molar ratio of chloric(VII) acid to benzylamine was changed from 0.1 to 0.3. Upon increasing this ratio, the amount of HBIW formed increased, but the product was more contaminated. The lower yield is due to a greater extent of side reactions as more acid is used in the process. A successive series of the reactions was performed with gradually lowering quantity of the solvent. The catalyst to benzylamine ratio remained constant and equal to 0.10. During subsequent reactions, the concentration of the substrates in the reaction mixture gradually increased. The reaction yield increased from 76 to 81% when the methanol to benzylamine volume ratio changed from 7.0 to 3.5. Furthermore, the reactions with the stoichiometric glyoxal to benzylamine ratio were performed to achieve a reaction yield of 81.3%. After optimizing the reaction carried out in a 10 L reactor, the reaction yield increased by approximately 5% and the amount of the HBIW obtained was doubled from the volume unit of the reactor to approximately 180 g of HBIW/L. The increase of the HBIW synthesis scale from laboratory to large-laboratory scale proceeded with no major problems. The condensation reaction of glyoxal with benzylamine is weakly exothermic; no gases evolved in the course of its run, and the substrates are liquid and can be easily fed to the reactor. In this respect, further increasing the reaction scale should not involve any major challenges. Some problems may occur with the filtering and washing of the crude product because of its greasy consistency. Likewise, an increase in the scale of the purification process may be a challenge, as the crude product has to be returned to the reactor. 3.2. HBIW Synthesis on the Pilot Scale. Within the framework of a development project, a pilot-plant was designed and built (at the Chemical Works “NITRO−CHEM” S.A. in Bydgoszcz). The key units of the plant are a 300 L working capacity reactor equipped with an agitator and temperature sensor, a reflux condenser, raw-material metering tanks of 250, 60, 30, and 25 L capacity, and a vacuum filter with the 15 μm mesh filtering screen. The HBIW synthesis was carried out in conformity with the flow sheet presented in Figure 2. The newly built plant was used to perform a study on HBIW synthesis on a larger scale. The production scale was increased 30-times. The aim of the research was to confirm the expected possibility of producing HBIW on a pilot-plant scale. Reactions were performed in accordance with the description in section

Figure 2. Flow sheet of the HBIW synthesis and purification process.

2.3, increasing the amount of reagents to 210.0 kg of methanol, 15.0 kg of water, 9.9 kg (59.1 mol) of 60% chloric (VII) acid, 49.0 kg (453 mol) of benzylamine, and 30.1 kg (207 mol) of 40% glyoxal. Then, 600.0 kg of methanol and 0.5 kg (4.7 mol) of sodium carbonate were used for purification. The parameters of the syntheses and results of HBIW production are listed in Table 2. Table 2. Reaction Conditions and HBIW Yields Achieved in the Reactions Conducted in a 300 L Stainless-Steel Reactor no.

addition time [h]

reaction time [h]

1 2 3 4 5 6a

2 2 2 2 6 6

4 4 6 10 14 14

a

yield of crude HBIW, [kg (%)] 34.9 34.3 36.3 34.7 36.1 36.5

(71.2%) (70.0%) (74.1%) (70.8%) (73.7%) (83.1%)

purity (cryometric method [%]) 88.7 95.1 94.8 91.4 94.7 96.6

With 23% excess benzylamine.

Reactions 1 and 2 were performed in accordance with the description in section 2.3. The reactions proceeded with a similar yield. In the case of one of the reactions, the low purity (88.7%) product obtained was due to difficulties in filtering the reaction mixture and washing the product on a nutsche filter. The effect of the increased reaction duration and glyoxal addition times on this scale on the HBIW reaction yield were of particular interest (reactions 3−5). For syntheses 3 and 5, a minor increase in reaction yield was noted with the product purity remaining approximately the same. While separating the product in reaction 4, there were some problems with filtering C

DOI: 10.1021/acs.oprd.7b00101 Org. Process Res. Dev. XXXX, XXX, XXX−XXX

Organic Process Research & Development

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reaction again. This is related to the fact that sulfuric acid does not show oxidizing properties in contrast to chloric(VII) acid. The recycling of methanol and substitution of chloric(VII) acid with sulfuric(VI) acid will allow for reduction of the cost of reactants in the production of one HBIW weight unit by approximately 50%. Besides the cost of reagents, the overall cost of the HBIW weight unit formation is determined by the production ability of the installation. Thanks to the decrease in the synthesis duration, labor expenses are decreased and installation production ability is increased.

and washing of the product, which resulted in its inferior purity. One reaction was performed with 23% excess benzylamine. The reaction resulted in an increased yield of ∼10%. As expected, a product with higher purity (96.6%) was generated. One synthesis was also carried out in which the expensive chloric(VII) acid was replaced by sulfuric(VI) acid. The reaction run was similar to the reaction conducted in the presence of chloric(VII) acid. The amount of HBIW obtained (33.6 kg) and the yield were insignificantly lower (68.6%) than with the use of chloric (VII) acid. The purity of the HBIW thus obtained was also satisfactory and comparable with that formed under the previously described conditions. The transfer of the HBIW synthesis from large-laboratory scale to the pilot scale occurred with no major challenges. The reactions were successfully conducted in conformity with the originally conceived parameters in the pilot plant designed for this purpose. In one of the pilot-plant batches, approximately 35 kg of the product with a purity of approximately 95% was obtained. The HBIW yield in terms of reactor volume was at a level of 120 g of HBIW/L. Major problems, however, were faced at the crude product filtration stage. The vacuum filter originally employed proved to be inadequate, which to a considerable degree extended the time required for this operation. In designing the facility for the target commercial scale, recourse to other filtering techniques seems advisable. In the commercial-scale process, optimization of the process with respect to reduced production costs is of prime significance. The cost of the feedstock material is critical in cost estimates for this process. The raw material quantities required for one HBIW batch (35 kg) are as follows: 1100 kg of methanol, $358 USD; 49 kg of benzylamine, $245 USD; 10 kg of chloric (VII) acid, $425 USD; 28 kg of 40% glyoxal solution, $48 USD; and 0.5 kg of sodium carbonate,