Solubility of Four Aminobenzoate Esters in Water and Normal Alcohols at Several Temperatures

TABLE OF CONTENTS LIST OF TABLES • LIST OF FIGURES . . .

( nature of the esters, i.e., alkyl carbon number.
However, these data proved to be of limited utility in the correlation between theoretical and actual solubilities with respect to tbe polarity differences between solute and solvent.
iii (   TABLE OF CONTENTS   ABSTRACT   TABLE OF

II. TOPICAL LOCAL ANESTHETICS
Topical anesthetics differ from local anesthetics primarily in that their solubility in water makes them unsuitable for injection (2). They cannot penetrate the intact skin (keratinized surface), but they are rapidly absorbed by mucosal surfaces (J). The  The hydrophilic center, an amino group, is attracted to polar groups in the lipoprotein of the neural membrane (2) and binds to a receptor molecule, probably by dona tio n of a hydrogen bond (8), while the nonpolar, lipophilic por tion of the molecule attaches to the lipoid phase of the me mbrane.
(2). These chemical combinations stabilize the membrane potential and interfere with the generation and transmission of impulses along the nerve fibers (2, J, 6 , 8) .

HOMOLOGOUS SERIES AND NONELECTROLYTE SOLUBILITY
The solubility of nonelectrolytes has often been interpreted on the basis of polarity differences between solutes and solvents (9,10,11,12,13,14,15).  (9), and ·Paruta (10) in several alcohols, i.e., polar, hydrogen bonding solvents . The Hildebrand and Scott solubility parameter theory (11) was used in these studies to predict the points of maximum solubility in each solvent.
However, the magnitude of solubility depends upon specific ( solute-solvent interactions (12), and is not always predictable.
The solubility parameter, J is a measure of intermolecular forces or cohesion between molecules and is defined as "the square root of the energy of vaporization per cubic centimeter of a liquid." (18) The relation is [ 1 ] Where A Evap and V when the molecules are "sufficiently alike so that they are under the same forces in the mixture as in the pure liquids" (20), and provides a suitable model for comparing the nonideal behavior of nonelectrolytes in polar solvents.

IV. THERMODYNAMICS OF NONELECTROLYTE SOLUBILITY
When two solutions of similar physical properties are mixed and there is no evolution or absorption of heat, the resulting solution is termed "ideal" or "perfect 11 (21,22) and can be used as a reference state (2J  The total excess free energy is the difference between Equations 9 and 10, using the activity coefficient equation above [12] from which the partial molal excess free energy for the solute can be derived as FE = Rt lno; [ 1 J J A partial molal quantity is defined as "the rate of increase in the content of the system in that particular quantity while the component is being added to the system." (51) However, Hildebrand warns that the physical property of partial molal quantities cannot be attributed to "the molecules of one species alone," and that it is "really a pro- Entropy is related to structure (20) and indicates the probability of a combination between solute and solvent (56). Increased entropy of solution denotes a more probable state for such a system than do the separate pure solute and solvent (37). As the degree of randomness and disorder for a system increases, the entropy increases, but the free energy decreases (57). For

Melting Point Determinations
The average of the two calorimeter melting points for each aminobenzoate ester was converted to Celsius melting points by subtracting the temperature correction constant.
Since there was a close agreement in melting points between experimental and literature values for the esters, these compounds were used directly and without further purificati on. 5.    Table I.

J4
of solution, Sa (Table IV) Table IV. The diminishing difference between the two values for entropy of solution as the alkyl chain length increases is shown by the decrease in the ratio S b/S a in Table IV. s s Since the two values of the ideal solubilities from Equations J and 7 in Table III are  The heats of solution in Table IV can be compared with the heats of fusion in Table I to show that a    .µ (..) al M    (12,13,14,19).
The activity coefficients in Table VI are (Table VII).
Since the activity coefficients are high for the methyl ester (2.82 to 4.47) and decrease progressively to near unity for the butyl ester   In Table IV  The natural logarithmic solubilities of the aminobenzoates are linear with respect to both reciprocal temperature {1/T) in Figure 10, and the natural log of T (1n T) in Figure 11. The ent halpies and entropi e s obtained from the least squares analysis have been listed in Table IV.
The fact that the propyl ester was the only solute that had a negative enthalpy of mixing in water, perhaps indicates a greater hydrogen bonding of the water around the propyl than around the other esters.  Because the solubility of the esters in water is so low, the activities in Table VI and the partial excess free   energies in Table VII   The limitations and frustrations of solubility investigations has been succinctly summarized by Hildebrand: We seek the best or sometimes the poorest solvent for a certain solute. We s eldom want to know a solubility to, say, 1 percent and, indeed, we seldom control temperature or purity to a corresponding degree. If we do need a solubility to that accuracy we must rely upon measurement, better measurement, indeed, than many in the literature. All theory can do for us in that case is to select, out of the scores of solvents updn our shelves, the few likely to serve our   8. Because of their low solubility in water, the aminobenzoates have very high activity coefficients. The Hildebrand solubility parameter theory has been modified to include a dipole orientation force to explain this highly nonideal behavior.