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Supercritical fluid extraction of polar nitrogen containing-substances
High Pressure Chemical Engineering Ph. Rudolfvon Rohr and Ch. Trepp (Editors) 9 1996 Elsevier Science B.V. All rights reserved.
345
Supercritical Fluid Extraction of Polar Nitrogen Containing-Substances M. Niehaus*, U. Teipel, G. Bunte, H. Krause, W. Weisweiler Fraunhofer Institut ~ r Chemische Technologie (ICT), Joseph von Fraunhofer Str. 7, D-76327 Pfinztal, Germany
ABSTRACT The solvent supercritical carbon dioxide offers unique possibilitys, like non-toxicity and therefore reduction of environmental pollution or access to low-temperature processing resulting in additional process safety. Therefore knowledge to the influence of modifiers of the solubility of the polar substances is important for evaluating novel manufacturing techniques like the RESS or GAS-process. Dynamic supercritical fluid extraction of pentaerythrite-tetranitrate (PETN), nitroguanidine (NIGU) and cyclo-trimethylene-trinitramine (RDX) with pure and modified carbon dioxide indicated that all explosives except nitroguanidine were extracted though for cyclo-trimethylene-trinitramine and 3-nitro-l,2,4-triazole use of modifiers proved to be necessary. The results show the high capacity of modified supercritical carbon dioxide as a solvent in RESS and GAS processes.
1 INTRODUCTION
Supercritical carbon dioxide is a good solvent for a variety of substances. Due to low temperatures and pressures being necessary to achieve supercritical conditions, production techniques work under relatively mild conditions/1/. Another important feature of supercritical carbon dioxide is the gaslike viscosity causing favourable transport porperties, so that for example supercitical fluid extractions (SFE) are achieved faster than with traditional methods. Carbon dioxide is intoxic and so incurs less costs for disposal than conventional organic solvents/2/. Hence the use of supercritical carbon dioxide as a solvent for propellants and drugs is discussed both in analytical chemistry/3, 4/and processing technology/5, 6/. In contrast to conventional disposal techniques like burning, recycling of propellants prevents pollution and does not waste the high energetic content of the material/3/. Despite high investment costs, recycling of propellants might be a more economical alternative.
346 Production of fine, solvent free powders is of great importance in the pharmaceutical industry /5/. Conventional techniques produce particles with broad particle size distributions. Moreover, particles may be irregular or contain solvents. Hence the development of procedures such as Rapid Expansion of Supercritical Solutions (RESS) or the Gas Antisolvent Recrystallisation (GAS) is in progress/5, 6/
2 FUNDAMENTALS
Considering the phase equilibrium between liquid and gas phase, the allotment of the liquid phase rises with increasing pressure. An increase in temperature therefore diplaces the allotment of the liquid phase in favour of the gas phase. As pressure and temperature increase, the properties of the gas and liquid phase, for example density or dielectricity, get to be more and more identical. The critical point is defined as the temperature (To: critical temperature) and pressure (Pc critical pressure) at which the properties of the phases become identical and so merge into a single, supercritical phase. The critical point is a specific parameter for a substance and for carbon dioxide it is at To = 31.3 ~ and po = 73.8 bar/1/. The solvent capacity of supercritical carbon dioxide changes with the variation of density and ~so it can be easily modulated by the variation of pressure. Adding small amounts of co-solvents (modifiers) changes the chemical and physical properties, like the solvent capacity or the critical point. To ensure supercritical conditions it is thence crucial to know the critical parameters as a function of the modifier concentration. Table 1 lists the critical pressure and temperature as a function of the co-solvent concentration in carbon dioxide/2/. Table 1" Critical parameters of modified Mol% Aceton Methanol Modifier Tcin p~in T~in p~in ~ bar ~ bar 1 34.7 77.9 32.7 76.5 2 36.8 7 9 . 7 34.7 78.2 4 43.7 8 5 . 7 37.7 8 1 . 7 *: 3.77 Mol% n-propanol. **" 3.34 Mol%
carbon dioxide/7/ Ethanol n-Propanol T~m pcin ~ bar 3 2 . 7 76.6 35.7 '78.3 4 0 . 5 84.3 n-butanol
T~in ~ 35.5 39.1 47.2*
p~in bar 76.8 80.5 90.0*
i-Propanol
n-Butanol
T~in ~ 34.5 37.4 43.5
Tcin ~ 36.5 42.5 56.1"
p~in bar 76.2 79.3 85.1
pcin bar 80.3 87.5 108"
347 3 EXPERIMENTAL
Picture 1 shows the device for extracting samples using supercritical carbon dioxide/modifier mixtures. Extractions were made at 300 bar, 50 ~ in 30 minutes and with modifier concentrations not exceeding 4 mol%, thus ensuring supercritical conditions (tab. 1).
Picture 1: Apparatus for extracting samples using supercritical carbon dioxide/modifier mixtures. The supercritical fluid flushes the extraction cells with a volume of 10 ml and is then expanded in the restrictors. In order to prevent the drive out of solid particles, there are flits with 5 lam pore size at the ends of the extraction cell. With fluid expansion, extracted particles precipitate and are kept in the vials which contain an organic solvent for sampling. Measured average carbon dioxide currents at the end of the extractor were 12 liters at a temperature of 28 ~ and 1 bar pressure, resulting in a current of 0.81 ml/min carbon dioxide at the above-meti0ned extraction conditions. Extracts were cured with ultrasound for several minutes in order to separate remaining carbon dioxide from the washing solution and then they were quantitatively analysed with an HPLC apparatus made by Hewlett Packard, type 1048 B. Recovery R is defined as shown in equation 1:
R =
m Extrakt, Solut m Total, Solut
9 100
(1)
348 Table 2 lists mutual solubilities of the samples with different modifers for comparison with the extraction results. Table 3 lists the standard melting points and standard dipol-moments of the samples. Table 2:
Properties of modifiers and mutual solubilitvs with samples at 1 bar
Solvent
Dipolemoment (gasphase) in D 181
Melting point in ~
Solubility of Cyclo-trimethylenetrinitramine
Acetone Acetonitrile 2-Propanol Methanol
2.88 3.92 1.66 1.70
56 81.6 82 65
4.021 6.811 0.054 0.48
in ~7/100 ~ (23~ '
Table 3 Properties of the samples Sample Nitroguanidine 3-Nitro- 1,2,4triazole
Structure
'' '
/NH2 N :S NO2 HN=C \NH-NO2 L~N/N
Solubility of Pentaerythrittetranitrate in ~lOOg (23~ 14.922 18.664 0.040 0.500 .......
Solubility of 3-Nitro-1,2,4-triazole in g/100g (23~ 1.331 0.403 0.007 0.387
Pentaerythrittetranitrate
O2NO-~~O O2NOJ
Cyclotrimethylenetrinitramine NO2
~---ONO2
O2N~NAN/NO2
L.) I
NO2
Melting point in ~ Dipolemoment (Dioxan) in D
246/8/ 6.95/8/
183-186/9/ 6.74/9/
i41.3/8/ 2.48/8/
204/8/ 5.79/8/
4 RESULTS
Diagram 1 shows the recovery of cyclo-trimethylene-trinitramine as a function of the modifier concentration. Without co-solvents, the recovery of cyclo-trimethylene-trinitramine is about 0.8 percent, thus indicating complete insolubility in supercritical carbon dioxide. Small amounts of cyclo-trimethylene-trinitramine recovered may be due to material driven out with a particle diameter smaller than the diameter of the flits at the end of the extraction cell. Except for ethanol, all modifiers enhance the solvent capacity of the extraction fluid at 2 mol% and 4 mol%. Still, large enhancements only occur with carbon dioxide modified with cyclohexanon and especially with acetonitrile. The influence of different modifiers on extraction efficiency with a concentration of 4 mol% is pointed out in diagram 2. With pure supercritical carbon dioxide, only pentaerythrit-tetranitrate is recovered. Recovery of the other samples is below 1%, indicating no mutual solubilities with supercritical carbon dioxide. Using modifiers, recoveries of nitro-triazole and cyclotrimethylene-trinitramine can be greatly enhanced.
349 For example, a mixture of 4 mol% 2-propanol with carbon dioxide extracts up to 3 5 percent of nitro-triazole and a mixture of 4 mol% acetonitrile extracts up to 95 percent of cyclotrimethylene-trinitramine. Different modifiers lead to different effects for the samples, thus indicating the specific interactions between modifier and solute. The comparison of the results with the mutual solubilities of solute and modifier at standard conditions (table 2) and with the standard dipole moments (table 2, 3) proves, that there is no correlation and therefore suitable modifiers must be found empirically. Chemical interactions dominate strongly, so that there is no possibility to correlate the influence of dipole moments with solubility. Results indicate the good potential for pentaerythrit-tetranitrate in establishing the RESS process for the production of fine particles. The GAS process could be more suited for particle formation of nitroguanidine, cyclo-trimethylene-trinitramine and nitro-triazole. If additional small amounts of modifiers are acceptable, then the flexible handling of both RESS - and GASprocess can be proposed for cyclo-trimethylene-trinitramine and nitro-triazole.
5 LITERATURE McHugh M, Krukonis V., Supercritical Fluid Extraction, Butterworth-Heinemann, Boston, 2nd Edition, 1994 De Castro L., Valcb.rel M., Tena M.T., Analytical Supercritical Fluid Extraction, Springer Verlag, Berlin, 1st. Edition, 1994 Morris J., McNesby K., Pesce-Rodriguez R., Extraction of Nitramine Propellants using Supercritical Fluids', 24th Int. Annu. Conf. ICT of Energetic Materials: Insensivity and Environmental Awareness, pp. 37-1/37-12, 1993 Jenkins T., Davidson G., PoliakoffM., Comparison of Xe and C(92as Mobile Phase in On-Line SFC-FTIR: Chromatographic Considerations, Journal of High Resolution Chromatography, Vol. 15, pp. 819-826, 1992 Tom J., Lim G., Debenedetti P., Prud'homme R., Applications of Supercritical Fluids in the Controlled Release of Drugs, Supercritical Fluid Engineering Science: Fundamentals and Applikations, pp. 238-257, 1993 Gallagher P., Coffey M., Krukonis V., Gas Anti-Solvent Recrystallization of RDX: I~brmation of Ultra-fine Particles of a Difficult to Comminute Explosive, The Journal of Supercritical Fluids, No.5, pp. 130-142, 1992 Gurdial G., Foster N., Tilly K., Supercritical Fluid Engineering Science, Fundamentals and App#cations, ACS Symposium Series, No. 514, pp. 45-53, 1993 Weast R., Handbook of Chemistry and Physics, 49th Edition, CRC-Press, Cleveland (Ohio), 1968 Pevzner M., Fedorova E., Heterocyclic Nitro Compounds, 4. Dipole Moments of 3(5)Nitro-l,2,4-Triazoles, Chem. Het. Compd. (Engl. Transl.), Vol. 7, pp. 252-254, 1971
350
Diagram 1
Influence of modifier-concentration on recovery of cyclo-trimethylenetrinitramine
Diagram 2: Recovery of samples as a function of modifier
345
Supercritical Fluid Extraction of Polar Nitrogen Containing-Substances M. Niehaus*, U. Teipel, G. Bunte, H. Krause, W. Weisweiler Fraunhofer Institut ~ r Chemische Technologie (ICT), Joseph von Fraunhofer Str. 7, D-76327 Pfinztal, Germany
ABSTRACT The solvent supercritical carbon dioxide offers unique possibilitys, like non-toxicity and therefore reduction of environmental pollution or access to low-temperature processing resulting in additional process safety. Therefore knowledge to the influence of modifiers of the solubility of the polar substances is important for evaluating novel manufacturing techniques like the RESS or GAS-process. Dynamic supercritical fluid extraction of pentaerythrite-tetranitrate (PETN), nitroguanidine (NIGU) and cyclo-trimethylene-trinitramine (RDX) with pure and modified carbon dioxide indicated that all explosives except nitroguanidine were extracted though for cyclo-trimethylene-trinitramine and 3-nitro-l,2,4-triazole use of modifiers proved to be necessary. The results show the high capacity of modified supercritical carbon dioxide as a solvent in RESS and GAS processes.
1 INTRODUCTION
Supercritical carbon dioxide is a good solvent for a variety of substances. Due to low temperatures and pressures being necessary to achieve supercritical conditions, production techniques work under relatively mild conditions/1/. Another important feature of supercritical carbon dioxide is the gaslike viscosity causing favourable transport porperties, so that for example supercitical fluid extractions (SFE) are achieved faster than with traditional methods. Carbon dioxide is intoxic and so incurs less costs for disposal than conventional organic solvents/2/. Hence the use of supercritical carbon dioxide as a solvent for propellants and drugs is discussed both in analytical chemistry/3, 4/and processing technology/5, 6/. In contrast to conventional disposal techniques like burning, recycling of propellants prevents pollution and does not waste the high energetic content of the material/3/. Despite high investment costs, recycling of propellants might be a more economical alternative.
346 Production of fine, solvent free powders is of great importance in the pharmaceutical industry /5/. Conventional techniques produce particles with broad particle size distributions. Moreover, particles may be irregular or contain solvents. Hence the development of procedures such as Rapid Expansion of Supercritical Solutions (RESS) or the Gas Antisolvent Recrystallisation (GAS) is in progress/5, 6/
2 FUNDAMENTALS
Considering the phase equilibrium between liquid and gas phase, the allotment of the liquid phase rises with increasing pressure. An increase in temperature therefore diplaces the allotment of the liquid phase in favour of the gas phase. As pressure and temperature increase, the properties of the gas and liquid phase, for example density or dielectricity, get to be more and more identical. The critical point is defined as the temperature (To: critical temperature) and pressure (Pc critical pressure) at which the properties of the phases become identical and so merge into a single, supercritical phase. The critical point is a specific parameter for a substance and for carbon dioxide it is at To = 31.3 ~ and po = 73.8 bar/1/. The solvent capacity of supercritical carbon dioxide changes with the variation of density and ~so it can be easily modulated by the variation of pressure. Adding small amounts of co-solvents (modifiers) changes the chemical and physical properties, like the solvent capacity or the critical point. To ensure supercritical conditions it is thence crucial to know the critical parameters as a function of the modifier concentration. Table 1 lists the critical pressure and temperature as a function of the co-solvent concentration in carbon dioxide/2/. Table 1" Critical parameters of modified Mol% Aceton Methanol Modifier Tcin p~in T~in p~in ~ bar ~ bar 1 34.7 77.9 32.7 76.5 2 36.8 7 9 . 7 34.7 78.2 4 43.7 8 5 . 7 37.7 8 1 . 7 *: 3.77 Mol% n-propanol. **" 3.34 Mol%
carbon dioxide/7/ Ethanol n-Propanol T~m pcin ~ bar 3 2 . 7 76.6 35.7 '78.3 4 0 . 5 84.3 n-butanol
T~in ~ 35.5 39.1 47.2*
p~in bar 76.8 80.5 90.0*
i-Propanol
n-Butanol
T~in ~ 34.5 37.4 43.5
Tcin ~ 36.5 42.5 56.1"
p~in bar 76.2 79.3 85.1
pcin bar 80.3 87.5 108"
347 3 EXPERIMENTAL
Picture 1 shows the device for extracting samples using supercritical carbon dioxide/modifier mixtures. Extractions were made at 300 bar, 50 ~ in 30 minutes and with modifier concentrations not exceeding 4 mol%, thus ensuring supercritical conditions (tab. 1).
Picture 1: Apparatus for extracting samples using supercritical carbon dioxide/modifier mixtures. The supercritical fluid flushes the extraction cells with a volume of 10 ml and is then expanded in the restrictors. In order to prevent the drive out of solid particles, there are flits with 5 lam pore size at the ends of the extraction cell. With fluid expansion, extracted particles precipitate and are kept in the vials which contain an organic solvent for sampling. Measured average carbon dioxide currents at the end of the extractor were 12 liters at a temperature of 28 ~ and 1 bar pressure, resulting in a current of 0.81 ml/min carbon dioxide at the above-meti0ned extraction conditions. Extracts were cured with ultrasound for several minutes in order to separate remaining carbon dioxide from the washing solution and then they were quantitatively analysed with an HPLC apparatus made by Hewlett Packard, type 1048 B. Recovery R is defined as shown in equation 1:
R =
m Extrakt, Solut m Total, Solut
9 100
(1)
348 Table 2 lists mutual solubilities of the samples with different modifers for comparison with the extraction results. Table 3 lists the standard melting points and standard dipol-moments of the samples. Table 2:
Properties of modifiers and mutual solubilitvs with samples at 1 bar
Solvent
Dipolemoment (gasphase) in D 181
Melting point in ~
Solubility of Cyclo-trimethylenetrinitramine
Acetone Acetonitrile 2-Propanol Methanol
2.88 3.92 1.66 1.70
56 81.6 82 65
4.021 6.811 0.054 0.48
in ~7/100 ~ (23~ '
Table 3 Properties of the samples Sample Nitroguanidine 3-Nitro- 1,2,4triazole
Structure
'' '
/NH2 N :S NO2 HN=C \NH-NO2 L~N/N
Solubility of Pentaerythrittetranitrate in ~lOOg (23~ 14.922 18.664 0.040 0.500 .......
Solubility of 3-Nitro-1,2,4-triazole in g/100g (23~ 1.331 0.403 0.007 0.387
Pentaerythrittetranitrate
O2NO-~~O O2NOJ
Cyclotrimethylenetrinitramine NO2
~---ONO2
O2N~NAN/NO2
L.) I
NO2
Melting point in ~ Dipolemoment (Dioxan) in D
246/8/ 6.95/8/
183-186/9/ 6.74/9/
i41.3/8/ 2.48/8/
204/8/ 5.79/8/
4 RESULTS
Diagram 1 shows the recovery of cyclo-trimethylene-trinitramine as a function of the modifier concentration. Without co-solvents, the recovery of cyclo-trimethylene-trinitramine is about 0.8 percent, thus indicating complete insolubility in supercritical carbon dioxide. Small amounts of cyclo-trimethylene-trinitramine recovered may be due to material driven out with a particle diameter smaller than the diameter of the flits at the end of the extraction cell. Except for ethanol, all modifiers enhance the solvent capacity of the extraction fluid at 2 mol% and 4 mol%. Still, large enhancements only occur with carbon dioxide modified with cyclohexanon and especially with acetonitrile. The influence of different modifiers on extraction efficiency with a concentration of 4 mol% is pointed out in diagram 2. With pure supercritical carbon dioxide, only pentaerythrit-tetranitrate is recovered. Recovery of the other samples is below 1%, indicating no mutual solubilities with supercritical carbon dioxide. Using modifiers, recoveries of nitro-triazole and cyclotrimethylene-trinitramine can be greatly enhanced.
349 For example, a mixture of 4 mol% 2-propanol with carbon dioxide extracts up to 3 5 percent of nitro-triazole and a mixture of 4 mol% acetonitrile extracts up to 95 percent of cyclotrimethylene-trinitramine. Different modifiers lead to different effects for the samples, thus indicating the specific interactions between modifier and solute. The comparison of the results with the mutual solubilities of solute and modifier at standard conditions (table 2) and with the standard dipole moments (table 2, 3) proves, that there is no correlation and therefore suitable modifiers must be found empirically. Chemical interactions dominate strongly, so that there is no possibility to correlate the influence of dipole moments with solubility. Results indicate the good potential for pentaerythrit-tetranitrate in establishing the RESS process for the production of fine particles. The GAS process could be more suited for particle formation of nitroguanidine, cyclo-trimethylene-trinitramine and nitro-triazole. If additional small amounts of modifiers are acceptable, then the flexible handling of both RESS - and GASprocess can be proposed for cyclo-trimethylene-trinitramine and nitro-triazole.
5 LITERATURE McHugh M, Krukonis V., Supercritical Fluid Extraction, Butterworth-Heinemann, Boston, 2nd Edition, 1994 De Castro L., Valcb.rel M., Tena M.T., Analytical Supercritical Fluid Extraction, Springer Verlag, Berlin, 1st. Edition, 1994 Morris J., McNesby K., Pesce-Rodriguez R., Extraction of Nitramine Propellants using Supercritical Fluids', 24th Int. Annu. Conf. ICT of Energetic Materials: Insensivity and Environmental Awareness, pp. 37-1/37-12, 1993 Jenkins T., Davidson G., PoliakoffM., Comparison of Xe and C(92as Mobile Phase in On-Line SFC-FTIR: Chromatographic Considerations, Journal of High Resolution Chromatography, Vol. 15, pp. 819-826, 1992 Tom J., Lim G., Debenedetti P., Prud'homme R., Applications of Supercritical Fluids in the Controlled Release of Drugs, Supercritical Fluid Engineering Science: Fundamentals and Applikations, pp. 238-257, 1993 Gallagher P., Coffey M., Krukonis V., Gas Anti-Solvent Recrystallization of RDX: I~brmation of Ultra-fine Particles of a Difficult to Comminute Explosive, The Journal of Supercritical Fluids, No.5, pp. 130-142, 1992 Gurdial G., Foster N., Tilly K., Supercritical Fluid Engineering Science, Fundamentals and App#cations, ACS Symposium Series, No. 514, pp. 45-53, 1993 Weast R., Handbook of Chemistry and Physics, 49th Edition, CRC-Press, Cleveland (Ohio), 1968 Pevzner M., Fedorova E., Heterocyclic Nitro Compounds, 4. Dipole Moments of 3(5)Nitro-l,2,4-Triazoles, Chem. Het. Compd. (Engl. Transl.), Vol. 7, pp. 252-254, 1971
350
Diagram 1
Influence of modifier-concentration on recovery of cyclo-trimethylenetrinitramine
Diagram 2: Recovery of samples as a function of modifier