Anti-solvent

Propane deasphalting uses propane as an anti-solvent for asphaltenes. 

Manufacture of rhodium precatalysts for asymmetric hydrogenation. Established literature methods used to make the Rh-DuPhos complexes consisted of converting (1,5-cyclooctadiene) acetylacetonato Rh(l) into the sparingly soluble bis(l,5-cyclooctadiene) Rh(l) tetrafluoroborate complex which then reacts with the diphosphine ligand to provide the precatalyst complex in solution. Addition of an anti-solvent results in precipitation of the desired product. Although this method worked well with a variety of diphosphines, yields were modest and more importantly the product form was variable. The different physical forms performed equally as well in hydrogenation reactions but had different shelf-life and air stability. 

Gas [Gas anti-solvent] A process for separating dissolved materials by selective precipitation with added supercritical carbon dioxide. First used for recrystallizing the explosive RDX subsequently used for recrystallizing other explosives, pharmaceuticals, fine chemicals, and food products. 

PCA [Precipitation with a compressed anti-solvent] A process for making a solid with unusual morphology by spraying a solution of it into a supercritical fluid. The process resembles spray drying into a supercritical fluid. Used for making microspheres, microporous fibers, and hollow microporous fibers. 

C02 as anti-solvent The introduction of C02 to a reaction mixture selectively precipitates the organometallic hydrogenation catalysts, followed by SCF extraction of the products and recovery of the catalyst in active form. 

U. Foerter-Barth, U. Teipel, and H. Krause, Formation of particles by applying the gas anti-solvent (GAS) process, in Nottingham, 1999 Supercritical fluids Chemistry and Materials, Institut National Polytechnique de Lorraine, pp. 175-180. 

Note that in Eqn. 3, X] and X2 are evaluated at the same temperature. Max and Mt are mass of anti-solvent and total mass respectively. 

In some mixture design problems (such as formulations), it may not be necessary to consider processing issues and hence we would not have the process model constraints. In this case the problem becomes a simple mixing problem, which would already have been addressed by the miscibility criteria in sub-problem 4M. Hence, for these problems, we will not need sub-problem 5M. Also in some cases we might have to identify a mixture whose constituents perform different functions such as solvents and anti solvents for crystallization. In such cases we would have to formulate and solve more than one single compound design problems to identify the constituents and then solve the final two sub-problems to identify the optimal mixture. In certain cases we may not have process model constraints, however, we may still have to solve an optimization problem with other constraints, in sub-problem 4 and sub-problem 5m respectively. 

This CAMD mixture design (solvent/anti-solvent) problem is formulated as an MINLP model as shown below. The objective function and the various property constraints in the model are discussed subsequently... 

In the above MINLP model, the potential recovery is the objective function (Eqn. 26) subject to other property and phase equilibrium constraints (Eqn s. 27-40). The decisions that need to be made are the identities of the solvent and anti-solvent (binary variables) and the composition of solvent and anti-solvent... 

Since in this mixture design problem we have to identify a mixture whose constituents perform different functions, i.e., the solvent needs to have high solubility for the solute while the anti-solvent needs to reduce the solubility, we have to solve two different single compound design problems (involving subproblem 1M, 2m and 3M) to identify the candidate solvents and anti-solvents. The mutually miscible pairs are identified in sub-problem 4M and the final optimisation problem is solved in sub-problem 5M. 

The structural constraints used in the first case study namely, Eqn s 27,28 and 29 are used again. The melting point, boiling point and flash point, are used as constraints for both solvent and anti-solvent. Since the solvent needs to have high solubility for solute and the anti-solvent needs to have low solubility for the solute limits of 17 <8 < 19 and 5 > 30 (Eqn s. 33 and 37) are placed on the solubility parameters of solvent and anti-solvents respectively. Eqn.38 gives the necessary condition for phase stability (Bernard et al., 1967), which needs to be satisfied for the solvent-anti solvent pairs to be miscible with each other. Eqn. 39 gives the solid-liquid equilibrium constraint. 

This problem encompasses two single compound CAMD problems, namely design of solvent and anti-solvent and then identification of optimal mixture pair and its composition. The single component solvent design problem is the same as in case study 1 (Sub-problems 1, 2 and 3). The 10 molecules that are designed in the first case study are considered here. The single component antisolvent design proceeds as follows... 

The four pure component properties for anti-solvents (Eqn s 34,35,36 and 37) are considered in sub-problem 2. Out of the 2691 molecular structures, 5 satisfied these constraints. Note that these 5 anti-solvents are different from the 10 solvents identified before. 

Since we do not have any mixture property constraints related to single compound anti-solvent design this sub-problem was ignored. 

Now we have 10 solvents and 5 anti-solvents, which satisfy their respective constraints. The optimal pair of solvent/anti-solvent and their mixture compositions is identified with the help of sub-problems 4Mand 5M. 

The miscibility of solvent anti-solvent pairs is considered in sub-problem 4M through constraint represented by Eqn.38. Only 6 pairs were found to be mutually miscible with each other. 

The above problem becomes an NLP problem when we fix the integer variables. Since we have only 6 feasible pairs, 6-NLP problems were solved by fixing the binary variables representing the solvent and anti-solvent in the 6 pairs. The molecular structures of the optimal solvent and anti-solvent mixture giving a maximum potential recovery of 69% ibuprofen is shown in Table 2. The properties of solvent and anti-solvent are shown in Table 3 and Table 4 respectively. 

Table 4 Design results of optimal anti-solvent for drowning out crystallization...

Cocrystals are often prepared by a traditional solution crystalhsation approach such as solvent evaporation, coohng, or anti-solvent addition. There are a number of reasons for the popularity of the solution-based approach. Solution crystallisation can yield large, well-formed single crystals, from which one may easily evaluate crystal habit and surface features. Analysis of the diffraction pattern of a single crystal is typically the best means of obtaining an absolute crystal structure determination. Further, solution crystalhsation is an established and effective purification step. 

The continuous reaction system could be combined with solid acid-catalyzed in situ racemization of the slow-reacting alcohol enantiomer [149]. The racemiza-tion catalyst and the lipase (Novozym 435) were coated with ionic liquid and kept physically separate in the reaction vessel. Another variation on this theme, which has yet to be used in combination with biocatalysis, involves the use of scC02 as an anti-solvent in a pressure-dependent miscibility switch [150]. 

Lactose may be obtained in two crystalline forms a-lactose and P-lactose (in addition to amorphous forms). The alpha form is obtained when water is incorporated into the lattice structure during crystallization (usually by supersaturation below 93.5°C) (5). Alternatively, the beta form does not contain water and exists as a non-hygroscopic and anhydrous form. Amorphous lactose is formed when either the crystallization is rapid or sufficient transient energy is introduced into the crystalline forms (74), i.e., spray drying (75), micronization and milling (76), freeze-drying, and anti-solvent crystallization (77). 

Solid/liquid separation is usually required at the interface of the primary and secondary stages to allow optional upgrading of the crude coal liquids of the primary liquefaction stage, by removing mineral matter, unreacted coal, heavy products, and catalysts (111, 112). Distillation, anti-solvent extraction, and centrifugation have been conventionally employed in liquefaction processes (113, 114). 

Micronization with supercritical fluids - Crystallization - Rapid expansion - Gas anti-solvent Recrystallization - Precipitation with compressed anti-solvent - Solution-enhanced dispersion - Particles from gas-saturated solutions 80 - 300 fine particles and powders from various products and of designed properties... 

Economical considerations are investigated in this section, with reference to high pressure extraction plants, to the production of polyethylene, and to the precipitation by supercritical anti-solvent process. 

Finally, the industrial application of a technique based on the precipitation by a supercritical anti-solvent is discussed it can be economically attractive only with high-value products, such as pharmaceutical ones. 

---