Gas Antisolvent Recrystallization: New Process To Recrystallize

Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on September 11, 2013 | http://pubs.acs.org Publication Date: August 29, 1989 | doi: 10.1021/bk-1989-0406.ch022

Chapter 22

Gas Antisolvent Recrystallization: New Process To Recrystallize Compounds Insoluble in Supercritical Fluids 1

1

1

2

P. M.Gallagher ,M. P.Coffey ,V.J.Krukonis ,and N. Klasutis l

2

Phasex Corporation, 360 Merrimack Street, Lawrence, MA 01843 Air Force Armaments Laboratory, Eglin Air Force Base, FL 32542-5435 The recrystallization of nitroguanidlne from Ν-methyl pyrrolidone and Ν,Ν-dimethyl formamide using supercritical fluids and gases near their vapor pressures as anti-solvents was investigated. The nitroguanidine used for the recrystallization study consisted of high aspect ratio needles, 5 x 100 microns; because of its low bulk density the as-produced nitroguanidine is not satisfactorily incorporated into explosives formulations at high solids loading. Depending upon the specific combinations of parameters, the particle size and size distribution could be varied over a wide range, e.g., spherical particles of 100 microns diameter (the desired shape and size), low aspect ratio crystals, unusual star -shaped clusters, loose spherical agglomerates, or monodisperse particles of one micron or less. The results presented for nitroguanidine define a quite general recrystallization concept for processing difficult-to-comminute solids.

The p a r t i c l e size and size d i s t r i b u t i o n of s o l i d materials produced i n i n d u s t r i a l processes are frequently not those desired f o r subsequent use of these materials, and as a r e s u l t , comminution and r e c r y s t a l l i z a t i o n operations are c a r r i e d out on a large scale i n the chemicals, pharmaceuticals, dyes, polymers, and explosives industries i n order to take a material from one s i z e or size d i s t r i b u t i o n and change it into another. The processes used to accomplish the p a r t i c l e size changes are as diverse as the materials they are practiced on. As examples of methods f o r p a r t i c l e size r e d i s t r i b u t i o n , there are simple crushing and grinding (which f o r some compounds are c a r r i e d out at cryogenic temperatures) b a l l m i l l i n g (with or without m i l l i n g a i d s ) , a i r micronizatfon (also c a l l e d j e t impingement or f l u i d energy m i l l i n g ) , sublimation, and recrystallization from solution. The latter technique, r e c r y s t a l l i z a t i o n , can be c a r r i e d out by several processes, e.g., thermal methods, using the temperature dependence o f s o l u b i l i t y , and anti-solvent methods using a non-solvent to decrease the s o l u b i l i t y 0097-6156/89/0406-0334$06.25/0 © 1989 American Chemical Society

In Supercritical Fluid Science and Technology; Johnston, K., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989.


22.

Gas Antisolvent Recrystallization

GALLAGHER ET AL.

335

of a s o l i d which i s dissolved i n a solvent. A d d i t i o n a l l y , chemical reactions o f soluble materials to produce an insoluble (and desired) product i s p r a c t i c e d on an i n d u s t r i a l scale i n the formation o f dyes and other products, the reactant concentration and product p r e c i p i t a t i o n c o n t r o l l e d to give the desired p a r t i c l e size distribution. There are p r a c t i c a l problems associated with many o f the above processes; f o r example, there are many materials that are d i f f i c u l t to process by grinding or s o l u t i o n techniques f o r one reason or another. Certain dyes, chemical intermediates, b i o l o g i c a l and pharmaceutical compounds which are "waxy" or " s o f t " , c e r t a i n s p e c i a l t y polymers, and explosives are a few categories of d i f f i c u l t to process materials. Supercritical fluids have been shown to be excellent r e c r y s t a l l i z a t i o n agents f o r a v a r i e t y o f materials, and t h e i r use i n r e c r y s t a l l i z i n g an explosive, nitroguanidlne (NQ), i s presented. A new process, GAS (gas anti-solvent) R e c r y s t a l l i z a t i o n , i s described. Background S u p e r c r i t i c a l f l u i d s have been used as solvents f o r a wide v a r i e t y o f extractive a p p l i c a t i o n s . Some s p e c i f i c examples are coffee and tea d e c a f f e i n a t i o n , hops and e s s e n t i a l o i l s e x t r a c t i o n , f r a c t i o n a t i o n of polymers ' , p u r i f i c a t i o n o f reactive monomers , e x t r a c t i o n of cholesterol from animal f a t s and eggs , and o t h e r s . Some o f the processes are i n production, and others are i n the research or advanced development stage. Gases such as carbon dioxide, the l i g h t hydrocarbons, e.g., ethane, ethylene and propane, and the chlorofluorocarbons have been used to advantage i n s p e c i f i c instances. These processes are based on the pressure-dependent solvent properties o f gases and l i q u i d s above t h e i r c r i t i c a l points f i r s t demonstrated i n 1879 by Hannay and Hogarth . Todd and E l g i n f i r s t described the use o f s u p e r c r i t i c a l f l u i d s f o r separating materials i n 1955 ; one or more materials i n a mixture can be dissolved i n a s u p e r c r i t i c a l f l u i d a t high pressure, and the material(s) can be recovered when the pressure i s reduced. The separation o f solutions o f l i q u i d s using s u p e r c r i t i c a l f l u i d s was reported i n 1959 by E l g i n and Weinstock . Recently, s u p e r c r i t i c a l f l u i d s have been investigated i n an important "non-extractive" a p p l i c a t i o n , v i z . , S u p e r c r i t i c a l F l u i d Nucleation » » » ' » » . In t h i s process a s o l i d i s dissolved i n a s u p e r c r i t i c a l f l u i d at some temperature and pressure conditions, and the s o l u t i o n i s expanded to some lower pressure l e v e l which causes the s o l i d to p r e c i p i t a t e . This concept has been demonstrated f o r a wide v a r i e t y o f materials including polymers , dyes and s t e r o i d s . By varying the process parameters that influence supersaturation and nucleation rates p a r t i c l e s can be obtained which are quite d i f f e r e n t i n s i z e and morphology from the parent material. S u p e r c r i t i c a l F l u i d Nucleation can be an a t t r a c t i v e r e c r y s t a l l i z i n g method f o r many s o l i d s , e s p e c i a l l y f o r some difficult-to-comminute or - r e c r y s t a l l i z e materials such as pharmaceuticals used i n dermal salves, i n j e c t a b l e solutions, and ophthalmological preparations which require u l t r a - f i n e and uniform p a r t i c l e s . As an example o f the f i n e p a r t i c l e s i z e formation c a p a b i l i t i e s o f S u p e r c r i t i c a l F l u i d Nucleation, Figures l a 1

2,3

5

4

6

7

8

9

1,4

10

11

12

13

14

15

16

17

18

19

14

14


19

SUPERCRITICAL

FLUID SCIENCE AND

TECHNOLOGY


336

Figure 1. (a) As produced progesterone, (b) r e c r y s t a l l i z e d from s u p e r c r i t i c a l carbon dioxide, 4000 p s l , 55°C expanded to ambient.



22.

G A L L A G H E R E T AL.


337

and l b show parent (as-received) progesterone and progesterone r e c r y s t a l l i z e d from s u p e r c r i t i c a l carbon dioxide; the r e c r y s t a l l i z e d progesterone exhibits a uniform 3 micron p a r t i c l e s i z e . One obvious requirement f o r the process o f S u p e r c r i t i c a l F l u i d Nucleation i s that the s o l i d material to be r e c r y s t a l l i z e d dissolve i n some s u p e r c r i t i c a l f l u i d to an "appreciable" extent. However, not a l l s o l i d s dissolve i n the simple s u p e r c r i t i c a l f l u i d s mentioned e a r l i e r , and, therefore, i t i s sometimes d i f f i c u l t to s a t i s f y the s o l u b i l i t y requirement. The use o f s u p e r c r i t i c a l f l u i d s and, a d d i t i o n a l l y , gases near t h e i r vapor pressures, as anti-solvents i s an a t t r a c t i v e alternative r e c r y s t a l l i z a t i o n technique f o r processing p a r t i c u l a r l y difficult-to-comminute or - r e c r y s t a l l i z e s o l i d s that are insoluble i n s u p e r c r i t i c a l f l u i d s . This method, termed GAS (gas anti-solvent) R e c r y s t a l l i z a t i o n , exploits the a b i l i t y o f gases to dissolve i n organic l i q u i d s and to lower the solvent power o f the l i q u i d for the compounds i n solution, thus causing the s o l i d s to precipitate. Although the media f o r r e c r y s t a l l i z a t i o n i n the respective processes are d i f f e r e n t , the p r i n c i p l e s o f p r e c i p i t a t i o n by GAS R e c r y s t a l l i z a t i o n are b a s i c a l l y the same as those i n operation in Supercritical F l u i d Nucleation. Furthermore, there are e s s e n t i a l l y no l i m i t a t i o n s f o r employing GAS R e c r y s t a l l i z a t i o n provided that c e r t a i n s o l u b i l i t y relationships e x i s t among the s o l i d material, the l i q u i d (solvent), and the gas (anti - solvent). I f an organic l i q u i d (which i s a solvent f o r the s o l i d to be r e c r y s t a l l i z e d ) and a gas are a t l e a s t p a r t i a l l y miscible, introduction of the gas into the l i q u i d s o l u t i o n w i l l r e s u l t i n expansion of the l i q u i d phase, reducing i t s solvent power for the s o l i d , and the s o l i d w i l l p r e c i p i t a t e . Depending upon parameters which influence the supersaturation r a t i o and the rate of p a r t i c l e growth and which are discussed subsequently, the c r y s t a l s i z e , s i z e d i s t r i b u t i o n , and shape can be varied over wide ranges. Experimental Methodology GAS R e c r y s t a l l i z a t i o n o f an explosive, nitroguanidlne (NQ), was studied. NQ i s not soluble i n carbon dioxide, the l i g h t hydrocarbons, and the chlorofluorocarbons, but i t i s soluble i n several organic l i q u i d s , e.g., N-methylpyrrolidone (NMP) and N,Ndimethyl formamide (DMF). I t was expected that several gases would be found soluble i n the two l i q u i d s , and thus, that GAS R e c r y s t a l l i z a t i o n could be used to r e c r y s t a l l i z e NQ. Several gases were screened for t h e i r expansion c h a r a c t e r i s t i c s with DMF and NMP using a standard 5000 p s i Jerguson gauge (Jerguson Valve and Gage Company, now a d i v i s i o n of Clark-Reliance, S t r o n g s v i l l e , OH). Carbon dioxide, chlorodifluoromethane (CFC-22), and dichlorodifluoromethane (CFC-12) were found to be miscible with both l i q u i d s over wide temperature-pressure ranges. In an i n t e r e s t i n g aside here, ethylene and ethane were found to be e s s e n t i a l l y insoluble i n the two l i q u i d s even a t pressure l e v e l s as high as 5000 p s i . For example, ethane d i d not expand the l i q u i d s at a l l , from which i t can be i n f e r r e d that the s o l u b i l i t y was n i l , and ethylene expanded the l i q u i d s less than f i v e percent. For comparison, l i q u i d hexane was also found to be insoluble i n DMF and NMP, and, thus, the i n s o l u b i l i t y o f ethane i s , perhaps, not


338

SUPERCRITICAL FLUID SCIENCE AND T E C H N O L O G Y

unexpected considering the s i m i l a r i t y i n the s o l u b i l i t y parameters of the two hydrocarbons, v i z . , about 7 ( c a l / c c ) * f o r l i q u i d hexane and about 6 f o r 5000 p s i ethane at 20°C*°, and because the s o l u b i l i t y parameter of DMF i s so high, v i z . , 12.1 at 20°C . On the other hand, the s o l u b i l i t y parameter of carbon dioxide i s also about 7 at 5000 p s i 20°C . In many systems hexane and carbon dioxide have been shown to be quite s i m i l a r i n t h e i r s o l u b i l i z i n g c h a r a c t e r i s t i c s ' ' , but with DMF and NMP carbon dioxide and hexane are very d i s s i m i l a r i n t h e i r behavior. Figure 2 shows the room temperature expansion behavior of carbon dioxide-DMF. At low pressure l e v e l s the expansion follows Henry's Law, i . e . , a straight l i n e , p-Hx path. At about 400 p s i the expansion increases markedly, and as the pressure approaches the vapor pressure of carbon dioxide, carbon dioxide and DMF become miscible. The expansion behavior shown i n Figure 2 i s obtained by observing the increase i n the volume of a known amount of the l i q u i d that has been charged to a volume-calibrated Jerguson gauge as the carbon dioxide i s introduced and mixed with the l i q u i d at increasing pressure l e v e l s . Higher temperature l e v e l s were not tested f o r the carbon dioxideDMF system, but as an example of the general e f f e c t of temperature on expansion of l i q u i d s by carbon dioxide, Figure 3 shows the expansion of cyclohexanone, a l i q u i d used i n other GAS R e c r y s t a l l i z a t i o n s t u d i e s ; as i s seen, higher temperature l e v e l s require higher pressure l e v e l s to reach s i m i l a r expansion l e v e l s . There i s a p o t e n t i a l f o r amine-carbon dioxide reactions to occur i n the nitroguanidlne system which i s the reason that carbon dioxide was not evaluated i n depth; instead chlorodifluoromethane and d i c h l o r o d i f l u o r ome thane were tested as anti-solvents f o r GAS R e c r y s t a l l i z a t i o n of NQ. Both chlorofluorocarbons expand DMF and NMP essentially identically. Since dichlorodifluoromethane is s u b s t a n t i a l l y more deleterious to the environment , and since the research was directed to the ultimate development of an i n d u s t r i a l process f o r r e c r y s t a l l i z i n g nitroguanidlne, c h l o r o d i f luorome thane was chosen as the preferred gas anti-solvent. The expansion behavior of c h l o r o d i f luorome thane and NMP at two temperature l e v e l s Is shown i n Figure 4. As the figure shows (and as d i d also Figures 2 and 3), the gas need not be s u p e r c r i t i c a l to expand a l i q u i d solvent; hence, the "G" i n the acronym GAS denotes the more general use of a "gas" as an anti-solvent. I n i t i a l r e c r y s t a l l i z a t i o n tests were c a r r i e d out i n the Jerguson gauge to determine the parameters, v i z . , i n i t i a l NQ concentration, rate of expansion, f i n a l pressure l e v e l , etc., that combine to y i e l d p a r t i c l e s of a c e r t a i n kind. I t i s d i f f i c u l t , i f not impossible, to predict a p r i o r i the p a r t i c l e s i z e , size d i s t r i b u t i o n , shape, and morphology that will result from specific combinations of experimental parameters, and, thus, i t i s informative to present some simple nucleation and p a r t i c l e growth theory insofar as the theory guided the course of the experimental investigation i n i t s early stages. 21

20


22

23

24

25

26

P r i n c i p l e s Underlying G^S R e c r y s t a l l i z a t i o n The

equilibrium

i n an assembly

of dissolved molecules which


can

GALLAGHER ET AL.


339


300 r

PRESSURE , psig Figure 2. Volumetric expansion o f DMF by carbon dioxide.

500

1000

1500

2000

PRESSURE , psig Figure 3. Volumetric dioxide.

expansion

of

cyclohexanone

by


carbon


340


300

r

P R E S S U R E , psig

Figure 4. Volumetric expansion of NMP by c h l o r o d i f luorome thane.


22.

GALLAGHER ET AL.

341


combine to form a c r i t i c a l nucleus beyond which s i z e favorable fluctuations w i l l cause the n u c l e i to grow has been described by Gibbs . (The term " c r i t i c a l " here does not r e l a t e to the c r i t i c a l point o f a gas or l i q u i d ; i t has been used by many authors to describe the s p e c i f i c nucleus s i z e that can subsequently grow to form particles.) Gibbs presented the conditions o f c r i t i c a l n u c l e i formation based upon free energy considerations , and Adamson gives an excellent treatment o f Gibbs' mathematical d e s c r i p t i o n . The formation o f an embryo, i . e . , an assembly o f molecules o f a s i z e smaller than the c r i t i c a l nucleus, requires that an interface between two phases form. Thus, the free energy o f the system w i l l have to increase i n i t i a l l y u n t i l an embryo reaches some c r i t i c a l diameter. Once the embryo i s o f s u f f i c i e n t s i z e , i . e . , o f the c r i t i c a l diameter described by Gibbs (and, i n c i d e n t a l l y , Gibbs used the term "globules'* to describe assemblies o f molecules), there are two competing modes of lowering the p a r t i c l e free energy: the nucleus can grow i n d e f i n i t e l y , or i t can shrink and disappear. C r i t i c a l n u c l e i w i l l grow at the expense o f s u b c r i t i c a l embryos so that the f i n a l p a r t i c l e size will be dependent upon some i n i t i a l critical nuclei concentration. Adamson also presents a readable development o f the rate equations describing nucleation f i r s t derived by Becker and Doring . Using the free energy considerations o f Gibbs, Becker and Doring derived an equation f o r the rate of formation o f n u c l e i of this c r i t i c a l size, v i z . , 27


27

AG

rate - Ze' itax /

R

28

T

(1)

where Ζ

Δ 6

i s the c o l l i s i o n frequency, c a l c u l a b l e from k i n e t i c theory and

ΙΜΧ

classical

i s the Gibbs free energy expression which derives from nucleus surface energy considerations and i s given below.

The free energy r e l a t i o n i s AG

mex " B/[RTln S ]

2

(2)

where Β

i s a constant derivable from p h y s i c a l properties o f the system,

S

i s the supersaturation r a t i o . (For purposes o f i l l u s t r a t i o n , i n a v a p o r - l i q u i d system S i s the r a t i o of actual component pressure to the normal vapor pressure; i n a system involving a solute dissolved i n a solvent, S i s the r a t i o o f actual concentration to saturation concentration.)

From Equations 1 and 2 i t i s seen that the nucleation rate i s very strongly influenced by the supersaturation r a t i o . As an example of the rapid increase i n the nucleation rate as supersaturation i s increased, Adamson shows f o r the condensation of water vapor that the


342

SUPERCRITICAL FLUID SCIENCE A N D T E C H N O L O G Y

number of n u c l e i formed (per second per cc f o r water vapor at 0°C) i s only 10" at a supersaturation r a t i o of 3.5 whereas i t i s 10 at a r a t i o of 4.5. The r a t i o at which the nucleation rate changes from imperceptible (e.g., 10* ) to very large (e.g., 10 ) Is termed the c r i t i c a l supersaturation r a t i o . The rate o f nucleation at that point i s termed catastrophic, and the phenomenon i s termed catastrophic nucleation. Equations 1 and 2 are s t r i c t l y applicable only to the homogeneous condensation of a vapor to l i q u i d droplets. In a two or three component system such as anti-solvent r e c r y s t a l l i z a t i o n , for example, or f o r r e c r y s t a l l i z a t i o n from a melt, other factors such as v i s c o s i t y of the medium, the mode of nucleation, i . e . , whether homogeneous or heterogeneous, etc., come into play, and the equations are modified by these other factors. Equations 1 and 2 are, nevertheless, of pedagogical value i n p r e d i c t i n g some general e f f e c t s of these other systems. The f i n a l p a r t i c l e s i z e that i s achieved i n any p a r t i c u l a r r e c r y s t a l l i z a t i o n s i t u a t i o n i s r e l a t e d to both the rate of formation of c r i t i c a l n u c l e i described above and by the rate of growth of these n u c l e i . The rate of molecule transport at the i n t e r f a c i a l boundary i s d i f f i c u l t to describe i n quantitative terms, but the o v e r a l l rate of growth of the n u c l e i , once they have been formed during the catastrophic period, and the e f f e c t of concentration on growth can be given by the mass transfer r e l a t i o n 8

3


8

3

flux of material to surface - kAAC

(3)

where k

i s a mass transfer c o e f f i c i e n t

A

i s the surface area of the p a r t i c l e at any p a r t i c u l a r instant

AC

i s the concentration d r i v i n g force at any p a r t i c u l a r instant; AC i s given by C-C^ (or i n words, the concentration of the component i n the gas minus i t s equilibrium concentration.)

In an anti-solvent r e c r y s t a l l i z a t i o n process, then, p a r t i c l e s i z e and p a r t i c l e s i z e d i s t r i b u t i o n i s determined by the i n t e r a c t i o n between the nucleation rate and the growth rate of c r y s t a l s , on one hand, and by the rate of creation of supersaturation, on the other hand; a l l three are influenced by the manner of addition of the a n t i solvent. Figure 5 i s a q u a l i t a t i v e picture of simultaneous events that occur when an anti-solvent i s added to a s o l u t i o n of a solute that i s to be r e c r y s t a l l i z e d . The three zones shown i n Figure 5, designated I, I I , and I I I , denote three areas of supersaturation. Zone I i s for a supersaturation less than 1, I.e., f o r actual solute concentrations less than saturation. No growth of p a r t i c l e s w i l l occur i n t h i s zone (and i n f a c t i f there are any p a r t i c l e s that are "somehow" present, they w i l l dissolve). In Zone I I , the supersaturation i s less than the c r i t i c a l value discussed e a r l i e r , but "some" nucleation can occur; p a r t i c l e s that are present i n this



GALLAGHER ET AL.

Gas Antisdvent Recrystallization

343

TIME

Figure 5. V a r i a t i o n o f supersaturation anti-solvent.

with rate o f addition o f



344

SUPERCRITICAL FLUID SCIENCE AND

TECHNOLOGY

zone can grow by the d l f f u s l o n a l mechanisms of Equation 3. Zone III represents very high supersaturation l e v e l s , and In t h i s regime catastrophic nucleation can occur. The four paths, A, B, C, and D, shown i n Figure 5 represent the events for four d i f f e r e n t rates of addition of anti-solvent, and they depict the simultaneous creation of supersaturation (by anti-solvent addition) and the consumption of supersaturation (by nucleation and growth). The rate of addition as indicated by Curve A i s low, and only very l i t t l e nucleation occurs when the supersaturation exceeds S-l. The Path A rate of addition i s so low that the rate of nucleation and the d l f f u s l o n a l growth of those (few) n u c l e i formed maintain the supersaturation below the c r i t i c a l value u n t i l the concentration of solute i n solution eventually f a l l s to saturation, S-l. Curve Β represents a higher rate of addition, high enough to exceed the c r i t i c a l supersaturation l e v e l . The s o l u t i o n i s rather more quickly depleted of solute by the higher rate of nucleation and the higher overall growth rate (and several nucleationsupersaturation decreases are denoted by the r e l a t i v e maxima and minima i n the curve) . The addition v i a Curve C i s a v a r i a n t of Curve B, v i z . , a s t i l l higher rate of anti-solvent addition. F i n a l l y , the rate of addition depicted by Curve D Is so high that almost a l l the solute i n s o l u t i o n i s consumed by the formation of n u c l e i , and the solute i n s o l u t i o n i s depleted almost s o l e l y by that mechanism. These nucleation and growth events are depicted d i f f e r e n t l y on a s o l u t i o n expansion-time p l o t i n Figure 6. The s t a r t i n g point on the v e r t i c a l axis i s that amount of expansion that r e s u l t s i n the onset of ( v i s i b l e ) nucleation. In the GAS R e c r y s t a l l i z a t i o n tests that were c a r r i e d out i n the Jerguson gauge, i t was found convenient to compare r e s u l t s using as a s t a r t i n g point the f i r s t appearance of p a r t i c l e s v i s i b l e to the unaided eye. The appearance of p a r t i c l e s , manifested as a haze, was termed the onset of nucleation, and the gas pressure which resulted i n s u f f i c i e n t expansion to cause t h i s nucleation to occur was termed the threshold pressure (THP). (The p a r t i c l e s at t h i s point are, of course, much larger than the "true" c r i t i c a l n u c l e i described by Gibbs; the Gibbs n u c l e i are assemblies of, perhaps, a few thousand molecules and, thus, they are i n v i s i b l e to the unaided eye.) Threshold pressure i s a function of s o l u t i o n concentration, the higher the concentration, the lower the pressure required to i n i t i a t e nucleation. Figure 6 summarizes the various experimental expansion paths that were investigated during the studies; the expected (and experienced) r e s u l t s are noted on the expansion paths. Starting at THP, (for s t r i c t accuracy, at the amount of expansion at THP), i f the subsequent expansion i s e s s e n t i a l l y n i l as shown by the Curve A expansion path, r e l a t i v e l y few n u c l e i are formed as r e l a t e d e a r l i e r ; they can grow to be large because there remains i n s o l u t i o n a r e l a t i v e l y large amount of solute a f t e r some n u c l e i are formed. Curves Β and C depict the f a s t e r rates of addition of gas a r t i solvent shown as Curves Β and C i n Figure 5; both rates of addition are s i m i l a r i n t h e i r e f f e c t s on s i z e and s i z e d i s t r i b u t i o n , i . e . , both w i l l r e s u l t In a wide d i s t r i b u t i o n , the s p e c i f i c f i n a l r e s u l t s a function of the p a r t i c u l a r rate of addition and concentration. Curve D represents an extremely high rate of expansion by rapid gas i n j e c t i o n and pressure r i s e ; e s s e n t i a l l y monodisperse and very small




GALLAGHER ET AL.

Small Crystals iMonodisperse | n

/~

/

/

y

/

I,-/

. /

Variable Size Discrete Size Distribution

/ Variable Size Continuous Size Distribution Large Crystals Monodisperse

TIME Figure 6. Expansion paths f o r a n t i - s o l v e n t

addition.



346

SUPERCRITICAL FLUID SCIENCE AND

TECHNOLOGY

p a r t i c l e s w i l l r e s u l t . Another path, Curve E, which was not shown i n Figure 5, i s included i n Figure 6 f o r completeness; a discrete p a r t i c l e size d i s t r i b u t i o n i s obtained by alternate gas i n j e c t i o n and a hold a t constant expansion f o r some period o f time, the gas injection-hold time sequence continued u n t i l the s o l u t i o n i s depleted i n solute. The various expansion paths shown p i c t o r i a l l y i n Figures 5 and 6 were investigated for t h e i r e f f e c t s on p a r t i c l e size and size d i s t r i b u t i o n , and generally the p a r t i c l e size and d i s t r i b u t i o n results could be correlated to the experimental procedure. Occasionally, however, some Inexplicable p a r t i c l e sizes and shapes were obtained. As stated e a r l i e r the i n i t i a l tests were c a r r i e d out i n a Jerguson gauge. A r e c r y s t a l l i z a t i o n test i s c a r r i e d out i n the following manner: an amount of NQ solution i s charged to the cavity of the Jerguson gauge. Gas i s admitted into the s o l u t i o n through a cotton f i l t e r located at the bottom of the cavity. The buoyant force propels the small bubbles of gas upward causing intimate mixing o f gas and l i q u i d r e s u l t i n g i n d i s s o l u t i o n of gas into the l i q u i d and causing the l i q u i d to expand. P a r t i c l e s o f NQ form a t "some" l e v e l of expansion as described e a r l i e r , and they s e t t l e to the bottom o f the cavity. Depending upon the s p e c i f i c expansion path, a test i s completed i n a period of a few seconds or up to one hour. After the p a r t i c l e s have s e t t l e d , the solute-depleted solution i s drained from the cavity through the f i l t e r , and the p a r t i c l e s are trapped on the cotton. Fresh gas Is then introduced u n t i l l i q u e f a c t i o n pressure i s reached; the solvent adhering to the p a r t i c l e s i s dissolved i n the l i q u e f i e d gas, and the solution i s drained. The dried p a r t i c l e s are sampled v i a a long r e t r i e v e r and are examined by o p t i c a l microscopy. Depending upon p a r t i c l e size and morphology and depending upon the c h a r a c t e r i s t i c s desired to be accented, p a r t i c l e s were examined under magnification o f 60 to 500X using either transmitted or r e f l e c t e d light. Results and Discussion Figure 7 i s a photomicrograph of the nitroguanidlne used for GAS R e c r y s t a l l i z a t i o n studies. (The scale marker designates 100 microns on t h i s and subsequent figures.) The primary p a r t i c l e s are seen to be high aspect r a t i o needles, about 100 microns long by about 5 microns i n cross section. With a very rapid expansion path, i . e . , addition o f gas within a period of a few seconds, the NQ p a r t i c l e s that were formed were very small and regular, of the order of a few microns i n s i z e . (For most f a c i l e presentation conditions are given i n the figure captions.) The u l t r a - f i n e p a r t i c l e s that were formed were e s s e n t i a l l y the same f o r carbon dioxide i n j e c t i o n or f o r chlorodifluoromethane or dichlorodifluoromethane i n j e c t i o n into NQ solutions over a wide NQ concentration range from 1 to 10X (w/w). For example, Figures 8 and 9 show the material r e c r y s t a l l i z e d by rapid i n j e c t i o n o f carbon dioxide and c h l o r o d i f luorome thane, respectively, into NQ-DMF solution; NQ-NMP solutions behave the same with the rapid expansion path. Larger c r y s t a l s of NQ and a wider d i s t r i b u t i o n of p a r t i c l e sizes were produced with gas addition at an intermediate rate, e.g., by the addition v i a Curves Β and Ε of Figure 6. Figure 10 shows the



22.

GALLAGHER ET AL.


Figure 7. As received nitroguanidlne.

Figure 8. GAS R e c r y s t a l l i z e d NQ - small p a r t i c l e s formed from 12X NQ-DMF, rapid (5 sec) i n j e c t i o n of C0 to 750 p s i , 20°C 2


347


348


Figure 9. GAS R e c r y s t a l l i z e d NQ - small p a r t i c l e s formed from 10X NQ-DMF, rapid (5 sec) i n j e c t i o n of chlorodifluoromethane to 75 p s i , 20°C.

Figure 10. GAS R e c r y s t a l l i z e d NQ - continuously varying p a r t i c l e size formed from 10X NQ-DMF by continuous addition o f chlorodifluoromethane to 180 p s i , 20°C.



22.

GALLAGHER ET AL.

Gas AntLsolvent Recrystallization

349

p a r t i c l e s formed by continuous addition o f anti-solvent, and a polydisperse p a r t i c l e s i z e d i s t r i b u t i o n i s evident. A d i f f e r e n t type of d i s t r i b u t i o n r e s u l t s with d i s c r e t e or step-wise expansion o f the solution; Figure 11 shows p a r t i c l e s formed when gas was added i n three steps, the f i r s t expansion to THP with a short hold, the next to an "intermediate" l e v e l o f about 75% expansion, and f i n a l l y a rapid r i s e to 150X. A trimodel d i s t r i b u t i o n r e s u l t e d . I n t e r e s t i n g l y , there i s a propensity f o r elongated growth o f NQ c r y s t a l s i n many o f the t e s t s , and even the very small p a r t i c l e s shown i n Figures 8 and 9 e x h i b i t a s l i g h t aspect r a t i o . Occasionally some " d i f f e r e n t shaped" NQ " p a r t i c l e s " were obtained during the GAS R e c r y s t a l l i z a t i o n t e s t s . Figure 12 shows p a r t i c l e s which resemble snowballs; the snowballs are quite f r i a b l e and are a c t u a l l y loose agglomerates o f primary p a r t i c l e s . The primary needle-shaped p a r t i c l e s that comprise the snowballs (and which are obtained by l i g h t l y smearing the snowballs on the microscopic s l i d e ) are shown i n Figure 13. Another unusual structure was seen only a t a c e r t a i n concentration l e v e l o f NQ i n DMF. Figure 14 shows these p a r t i c l e s , termed "starbursts", obtained during a s e r i e s o f tests investigating NQ concentration e f f e c t s . The starbursts are, l i k e the snowballs, also agglomerates o f primary p a r t i c l e s , but the starbursts are more coherent than the snowballs. A d d i t i o n a l l y , i t i s seen that the primary c r y s t a l s comprising the starbursts are larger i n crosssection than the needles comprising the snowballs o f Figure 12. Concerning the concentration e f f e c t s on starbursts, over the range o f 1 to 10X i n i t i a l concentration o f NQ ( i n DMF), the starbursts formed at about 3X, but not at higher or lower NQ concentrations, nor were they formed i n NMP s o l u t i o n . I f the expansion l e v e l i s very low and maintained a t THP, i . e . , i f expansion i s c a r r i e d out v i a Curve A a d d i t i o n shown i n Figures 5 and 6, larger p a r t i c l e s would be expected to form. Figure 15 shows such large p a r t i c l e s formed by very slow addition to the threshold pressure with expansion subsequently maintained a t t h i s value. Large, dense, regular p a r t i c l e s , i . e . , s p h e r i c a l or c u b i c a l i n shape, are desired f o r the explosive formulations. Closing Remaxfcs GAS R e c r y s t a l l i z a t i o n was d i r e c t e d to a s p e c i f i c explosive, nitroguanidlne, but the process i s quite general i n i t s c a p a b i l i t i e s of r e c r y s t a l l i z i n g v i r t u a l l y any s o l i d material provided that the s o l i d i s soluble i n some organic l i q u i d and that some gas i s soluble i n the l i q u i d s u f f i c i e n t l y to expand i t appreciably. The research i s currently a t the f e a s i b i l i t y stage, and t h i s paper reports some o f the I n i t i a l r e s u l t s . I t i s premature, therefore, to extend the r e s u l t s to, say, an economic evaluation o f the process a t some large production l e v e l . On the other hand, i t i s not premature to discuss some o f the p o t e n t i a l advantages o f GAS R e c r y s t a l l i z a t i o n . Gases that ate soluble i n l i q u i d s can be admixed "almost instantaneously", i . e . , complete expansion can be made to occur l i t e r a l l y within a few seconds, and, thus, extremely high supersaturation l e v e l s and nucleation rates can be attained r e s u l t i n g i n the formation o f extremely small p a r t i c l e s not r e a d i l y achievable by other processes. A f t e r the p a r t i c l e s have been f i l t e r e d , the solvent and anti-solvent



350


Figure 11. GAS R e c r y s t a l l i z e d NQ - discrete p a r t i c l e s i z e d i s t r i b u t i o n formed from 5X NQ-NMP, by stepwise addition of chlorodifluoromethane.

Figure 12. GAS R e c r y s t a l l i z e d NQ - snowballs formed from 8X NQDMF, moderate rate (5 min) i n j e c t i o n of c h l o r o d i f luorome thane to 180 p s i , 35°C.



22.

GALLAGHER ET AL.


Figure 13. Primary p a r t i c l e s comprising the snowballs o f Figure 12.

Figure 14. GAS R e c r y s t a l l i z e d NQ - starbursts formed from 3X NQDMF, 2.5 min i n j e c t i o n of chlorodif luorome thane to 110 p s i , 30°C. In Supercritical Fluid Science and Technology; Johnston, K., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1989.

351


352


Figure 15. GAS R e c r y s t a l l i z e d NQ - spheres formed from 5% NQ-NMP very slow chloro-di f l u o r ome thane i n j e c t i o n to 80 p s i (the threshold pressure) and hold time f o r 30 min, 22°C.



22.

GALLAGHER ET AL.


353

s o l u t i o n can be separated by simple pressure decrease, and with the use of the chlorofluorocarbons, f o r example, operating pressure l e v e l s can be below 100 p s i . Because non-polar (or only very s l i g h t l y polar) gases are used i n GAS R e c r y s t a l l i z a t i o n , the energy requirements during pressure decrease and separation can be small r e l a t i v e to d i s t i l l a t i o n of two polar l i q u i d s . Although i t was not discussed i n the experimental section, the s o l i d to be r e c r y s t a l l i z e d cannot be simultaneously "too" soluble i n the gas. For example, naphthalene cannot be r e a d i l y r e c r y s t a l l i z e d from l i q u i d s o l u t i o n v i a GAS R e c r y s t a l l i z a t i o n . S p e c i f i c a l l y , with the system naphthalene-toluene-carbon dioxide, only very narrow ranges of pressure and temperature can be used. As the carbon dioxide pressure i s r a i s e d to promote expansion of the toluene, and thus a decrease i n i t s d i s s o l v i n g power f o r naphthalene, the carbon dioxide i t s e l f becomes an increasingly good solvent f o r the naphthalene, and the naphthalene does not p r e c i p i t a t e under the competing forces of a decreased solvating power of an expanded toluene solvent and the increasing solvating power of carbon dioxide (Krukonis, V.J. Unpublished data). On the other hand, i f the s o l i d material i s soluble i n the gas, S u p e r c r i t i c a l F l u i d Nucleation exhibits the p o t e n t i a l f o r r e c r y s t a l l i z i n g the s o l i d d i r e c t l y . GAS R e c r y s t a l l i z a t i o n i s an e f f e c t i v e process f o r r e c r y s t a l l i z i n g a wide v a r i e t y of s o l i d materials, but as f o r any new process that i s to be evaluated, i t should be subjected to a c a r e f u l case-by-case evaluation f o r i t s economics r e l a t i v e to other r e c r y s t a l l i z a t i o n processes before i t i s c a r r i e d to advanced development. Acknowledgment The funding f o r t h i s work was provided by the A i r Force Armament Laboratory (AFATL), E g l i n AFB, FL 32542-5000, Contract F08635-87-C0346 and i s g r a t e f u l l y acknowledged. The complete r e s u l t s of the study are reported i n Reference 30.

Literature Citations 1. 2. 3. 4. 5. 6. 7. 8. 9.

McHugh, Μ. Α., Krukonis, V. J. Supercritical Fluid Extraction; Principles and Practice. Butterworth Publishing, Boston, 1986; Chapter 10, Appendix. Zosel, K. U.S. Patent 3,806,619, 1974. Vitzthum, O., and Hubert, P. U.S. Patent 4,167, 589, 1979. Stahl, Ε., Quirin K. W., Gerard, D. Dense Gases for Extraction and Refining: Springer Verlag, Berlin 1987, Ch. IV. Yilgor, I., McGrath, J. Ε., Krukonis, V. J. Polym. Bull. 1984, 12, 499. Elsbernd, C. S., Mohanty, D. Κ., McGrath, J. Ε., Gallagher, P. Μ., Krukonis, V. J. 194th ACS Mtg., New Orleans, September 1987. Krukonis, V. J. Polymer News 1985, 11, 7. Krukonis, V. J., Coffey, M. P., Bradley, R. L . , M. Korycka-Dahl, M., Kroll-Conner, P. L. Center for Dairy Research Conference, Milkfat: Trends and Utilization, Madison, April 1988. Best, D. Prepared Foods 1988, March, 124.


354

SUPERCRITICAL FLUID SCIENCE AND TECHNOLOGY


10.

Hannay, J. Β., Hogarth, J. Proc. Roy. Soc. (London) 1879, 29, 324. 11. Todd, D. B., Elgin, J. C. AIChE Jour. 1955, 1, 20. 12. Elgin, J. C., Weinstock, J. J. J. Chem. Eng. Data 1959, 4, 3. 13. Worthy, W. C&E News 1981, Aug 3, 16. 14. Krukonis, V. J. Ann. AIChE Mtg. San Francisco, November 1984. 15. Paulaltis, Μ. Ε., Krukonis, V. J., Kurnik, R. T., Reid, R. C. Chem. Eng. Rev. 1983, 1, 179. 16. Larsen, Κ. Α., King, M. L. Biotech. Prog. 1986, 2, 73. 17. Petersen, R. C., Matson, D. W., Smith, R. D. J. Am. Chem. Soc. 1986, 108, 2100. 18. Krukonis, V. J. 1st Int. Symp. Supercrit. Fluids Nice, October 1988. 19. Coffey, M. P., Krukonis, V. J. Supercritical Fluid Nucleation An Improved Ultra-Fine Particle Formation Process. Phasex Corp. Final Report to National Science Foundation 1988, Contr. ISI8660823. 20. King, J. W. 188th ACS Mtg., Philadelphia, August 1984. 21. Rodriguez, F. Principles of Polymer Systems 2nd ed. 1982, Hemisphere Publishing, New York, p 25. 22. Hyatt, J. A. JOC 1984, 49, 5097. 23. Allada, S. R., IEC Prod. Res. Dev. 1984, 23, 344. 24. Dandge, D. Κ., Heller, J. P., Wilson, Κ. V. IEC Prod. Res. Dev. 1985, 24, 162. 25. Krukonis, V. J., Coffey, M. P., Gallagher, P. M. Exploratory Development on a New Process to Produce Improved RDX Crystals: Supercritical Fluid Anti-Solvent Recrystallization. Phasex Corp. Final Rept. to U.S. Army Ballistics Research Laboratory, 1988, Contr. DAAA15-86-C-007. 26. MacKerron, C. Β., Hunter, D., Johnson, E . , Ushio, S. Chem. Eng. 1988, Jan 18, 22. 27. Gibbs, J. W. The Collected Works of J. W. Gibbs. Vol. I. Thermodynamics. Yale University Press, New Haven, 1957, p 322. 28. Adamson, A. W. Physical Chemistry of Surfaces. Interscience Publishers, Easton, PA, 1963, pp 288-298. 29. Becker, R. and Doring, W. Ann. Physik 1935, 24, 719. 30. Krukonis, V.J. and Gallagher, P.M. Exploratory Development on a New Nitroguanidine Recrystallization Process: GAS Anti-Solvent Recrystallization, Phasex Final Rept. to U.S. Air Force Armament Laboratory, 1988, Contr. F08635-87-C-0346. RECEIVED May 23,

1989


Gas Antisolvent Recrystallization: New Process To Recrystallize

Recommend Documents