Miscibility numbers

Godfrey gave an alternate approach for the prediction of mutual miscibility of solvents (Godfrey, 1972). As a measure of lipophilicity (that is, affinity for oil-like substances) the so-called miscibility numbers (M-numbers, with values between 1 and 31) have been developed. These are serial numbers of 31 classes of organic solvents, ordered empirically by means of simple test tube miscibility experiments and critical solution temperature measurements. There is a close correlation between M-numbers and Hildebrand s 5-values. 

The mutual miscibility of solvents that does not involve water has been reported on an empirical basis by assigning to each solvent a miscibility number, on a scale of standard solvents ranging from 1 for the very hydrophilic glycerol to 31 for the very lipophilic petrolatum. If the miscibility numbers of two solvents differ by < 15 they are probably miscible, whereas if they differ by > 17 they are probably immiscible. Those that have a miscibility number of 16 ought to be miscible with all solvents, hence act as universal solvents. The miscibility numbers are shown in Table 4.6, where, in the cases where two numbers are shown, the first pertains to miscibility with solvents of high lipophilicity and the second to miscibility with solvents of high hydrophilicity (Godfrey 1972). 

If the solvents are immiscible, the LC system will fail. If the pump will be delivering an eluent that is not soluble with the previous mobile phase or if the new mobile phase consists of two immiscible solvents, the net result is to have tiny slugs of different solvents traveling through the HPLC. Typical indications of this problem are (1) erratic flow rate, (2) noisy baseline, and/ or (3) baseline drift. To insure that these problems are not caused by a mismatch of solvents, refer to Table 6-4 for the miscibility numbers (M) and their use. The discussion on determining solvent miscibility using miscibility numbers is adapted from reference 20. 

Polarity Index Solvent Viscosity CP (20°) Boiling Point (°C, 760 Torr) Miscibility Number (M)... 

For a solvent that is not listed, the procedure for estimating the M number is to determine the cut-off point for miscibility using a sequence of known solvents. A correction term of 15 is then either added or subtracted, whichever is appropriate. Solvents used in these tests should of course be pure. After the miscibility number is determined, an experiment should be run to verify the solubility of the two solvents. For example, if a liquid has borderline solubility in dimethyl sulfoxide (M = 9), the M number assigned is 24. On the other hand, if an unknown liquid was borderline soluble in p-xylene (M = 24) its M number is estimated to be 9. Reference 20 has a list of approximately 400 liquids and should be consulted by those who are interested. 

Godfrey, N. B., Solvent selection via miscibility number. CHEMTECH, June, pp. 359-363 (1972). 

TABLE 15-3 Godfrey Miscibility Numbers (Conf/nuec/)... 

If C > B, then the solvent having miscibility number C is somewhat more lipophilic than the solvent having numbers A and B. At... 

If C < A, then the solvent having miscibility number C is somewhat less lipophilic than the solvent with numbers A and B. At this end of the lipophilicity scale, the number B characterizes the solvent s miscibility behavior. Apply rules 1 through 3, using A = B - C. 

If both members of a solvent pair have dual miscibility numbers, then the pair is likely to be miscible in all proportions at 25°C. 

Godfrey s method is a useful guide for compounds that exhibit behavior similar to the 31 standard solvents used to define miscibility numbers. The method deals with the common situation in which a mixture exhibits a UCST he. solubility tends to increase with... 

Solvent Refractive index (20 °C) Viscosity (cP) Miscibility number (> 1) Polarity (P )... 

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