Solubility represents the first and most important of these lipoidic properties. Characteristically, a lipoid has a greater solubility in neutral solvents than in water. This is explained by the fact that the two constituent groups, polar and nonpolar, induce different solubility properties.

As is well known, solubility corresponds to a free movement between molecules of the solvent and the solute. (25) Solubility is greater when the physical properties of the groups forming the solvent and those forming the solute are similar; it is impaired when they are different. Consequently, polar groups in a solute will tend to favor solubility in solvents with polar groups, such as water. At the same time, they will oppose solubility in neutral solvents formed by nonpolar groups. On the other hand, nonpolar groups in a substance will favor solubility in nonpolar neutral solvents but will oppose it in polar solvents such as water. Polar groups thus are hydro philic and lipophobic, while nonpolar are lipophilic and hydrophobic. (26)

While the solubility characteristics of substances composed only of polar or nonpolar groups are readily apparent, the problem is more complex when a substance contains both polar and nonpolar groups. Since such a compound possesses groups with antagonistic solubility tendencies, its solubility "in toto" will depend upon the relationship between the opposing forces. For a borderline group of polar nonpolar substances with approximately equal forces, there will be equal solubility in polar and non polar solvents. For other substances, the predominance of one or the other group will determine solubility characteristics. If the electrical forces of the polar group predominate, the substance will be hydrosoluble but insoluble or only partly soluble in nonpolar solvents. If, on the contrary, the cohesion—i.e., the van der Waals forces—of the nonpolar group predominate, the substance will be soluble in nonpolar solvents and less, or even not at all, soluble in water. (Table VI)

Polar and nonpolar forces can be calculated and their study can indicate the place of a substance in this systematization. The importance of solubility for defining and systematizing lipoids became apparent in a physicomathematical study of these substances carried out by Jean Mariani in our laboratories. (Note 2) We have defined as "hydroids" those substances with predominant polar groups which are more soluble in polar solvents such as water. The "borderline substances," with no predominance of either group, show the same solubility in polar and neutral solvents.

Table VI. Classification Of Chemical Compounds

Composition

Predominance

Name

Example

Polar groups only

Water

Polar nonpolar groups

Polar group predominant

Hydroides

Glycerin

No predominance

Borderline substances

n Propyl alcohol

Nonpolar group predominant

Lipoides

Oleic acid n Butyl alcohol

Nonpolar groups only

Paraffin

The "lipoids," in which the nonpolar groups predominate, are more soluble in neutral solvents than in water.

As we have mentioned above, from a practical point of view, a substance could be judged to be a hydroid, borderline substance, or lipoid by considering the differences in its solubility in water and in a nonpolar solvent, such as petroleum ether, which corresponds to a mixture of the first aliphatic saturated hydrocarbons liquid at normal temperature and pressure. A polar nonpolar substance more soluble in water than in neutral solvent is considered a hydroid; one equally soluble in both solvents is classified as a borderline substance; while a substance more soluble in the neutral solvent than in water is a lipoid.

Different polar groups such as COOH, OH, NH2, CO, SO2, SH, etc., enter into the constitution of various lipoids. They differ considerably in their electrostatic forces. As a result, the forces of the nonpolar groups required for predominance, if a lipoid is to be formed, also will differ. A different nonpolar group thus is necessary for each different polar group. For aliphatic molecules, it is principally the length of the chain which determines cohesion forces and a different number of carbons in the non polar group appears to be necessary, depending upon the polar group, in order to form a lipoid. The study of homologous series from this point of view is interesting.

Since the value of the electrostatic forces varies greatly from one polar group to another, the first members of the various homologous series, which are also lipoids, will differ from series to series, depending upon the nature of the polar group. The length of the carbon chain of the non polar group will thus indicate in what member of a series the lipoidic character appears. By comparing mathematically the value of the electrostatic forces of each polar group and the cohesion forces of the nonpolar group in the respective series, it is possible to determine which member of each homologous series of substances will first show the properties of the lipoids. This also can be determined experimentally, as seen above, using the solubility characteristics of the lipoids. For the different members of the series, degrees of solubility in a polar solvent such as water, and in a nonpolar solvent such as petroleum ether, were determined. The first member of an homologous series to be considered a lipoid was the one found to be more soluble in the nonpolar than in the polar solvent. All members with a large number of carbon atoms show lipoidic properties; those with fewer carbon atoms lack those properties.

Thus, lipoidic properties first become manifest, among the carboxylic acid series, in valeric acid, i.e., the five carbon member. The shorter carbon chain members are soluble to an equal or greater degree in water than in petroleum ether, while those having a carbon chain longer than four show a higher degree of solubility in the nonpolar solvents than in water. (Table VII)

Table VII. Solubilities Of Carboxylic Acid Homologues

% of solubility in

Nonpolar

No. of

Polar

Solvent

Carbon

Solvent

(Petroleum

Substance *

Common Name

Atoms

(Water at 20°)

Ether)

Methanoic acid

Formic acid

1

00

insol.

Ethanoic acid

Acetic acid

2

00

00

Propanoic acid

Propanoic acid

3

CO

oo

Butanoic acid

Butyric acid

4

00

00

Pentanoic acid

Valeric acid

5

3.7 (at 16°)

oo

Hexanoic acid

Caproic acid

6

0.4

00

Heptanoic acid

Enanthic acid

7

0.24

00

Octanoic acid

Caprylic acid

8

0.25 (at 100°)

00

* Names approved by International Union of Chemistry.

The same is true for the alkyl alcohols. n Propyl alcohol and the members below it are either miscible with both water and petroleum ether or more soluble in water, indicating that the nonpolar forces do not predominate in their molecules. Therefore, they are not lipoids. n Butyl alcohol, more soluble in neutral solvent than in water, thus is the first lipoidic member of this homologous series. However, this is not true for all its isomers. The primary, secondary and iso butanol are the first in their respective series to possess the solubility properties characteristic of lipoids. In the tertiary alcohol series, however, the four carbon member, the tert.-butanol, does not show the same solubility properties. Tert.-butanol is miscible with water and neutral solvent and as such, is not a lipoid. For this tertiary alcohol series, it is the five carbon member, the tert.-amyl alcohol, which first shows the solubility properties of a lipoid, being only 12.5% soluble in water and infinitely soluble in petroleum ether. Thus, of the four isomers of butyl alcohol, three are lipoids, while one, tert.-butyl alcohol, is not. (Table VIII)

Table VIII. Solubilities Of The Alkyl Alcohols

% of solubility in

Non-

Polar

polar

No. of

Solvent

Solvent

Carbon

(Water

(Petroleum

Substance *

Common Name

Atoms

at 20°)

Ether)

Methanol

Methyl alcohol

1

Ethanol

Ethyl alcohol

2

1-Propanol

Propyl alcohol

3

2-Propanol

Isopropyl alcohol

3

1 -Butanol

n Butyl alcohol

4

7.9

2-Butanol

sec Butyl alcohol

4

12.5

2-Methyl, 2-propanol

tert.-Butyl alcohol

4

2-Methyl, 1-propanol

Isobutyl alcohol

4

9.5

1-Pentanol

n Amyl alcohol

5

2.7

2-Pentanol

sec. act. Amyl alcohol

5

5.3

3-PentanoI

Diethyl carbinol

5

insol.

2-Methyl, 2-butanol

tert.-Amyl alcohol

5

12.5

2-Methyl, 1-butanol

n act. Amyl alcohol

5

insol.

3-Methyl, 2-butanol

Isoamyl sec. alcohol

5

si. sol.

1-Hexanol

n Hexyl alcohol

6

very si. sol.

2-Hexanol

sec.-Hexyl alcohol

6

very si. sol.

3-Hexanol

Ethyl propyl alcohol

6

0.9

1-Heptanol

n Heptyl alcohol

7

insol.

1-Octanol

n Octyl alcohol

8

insol.

* Names approved by International Union of Chemistry.

The same methods were used to recognize the first lipoidic members of various aikane derivatives studied. Table IX shows the first lipoid members of several homologous series.

Table IX. First Lipoidic Members In Various Alkane Derivative Homologous Series

Polar

No. of

Substance *

Common Name

Group

Carbon Atoms

Methanethiol

Methyl mercaptan

-SH

1

Propanal

Propionaldehyde

-CHO

3

Propylcarbylamine

Propyl isocyanide

-NC

3

1 -Butanol

n Butyl alcohol

-OH

4

2-Butanone

Butyl ketone

=CO

4

Butanamide

Butylamide

-CONH2

4

2-Methyl, 2-butanol

tert.-Amyl alcohol

-OH

5

Pentanoic acid (n)

Valeric acid

-COOH

5

Hexylamine (n)

Hexylamine

-NH2

6

1, 8 Octandiol

1, 8 Octandiol

-OH

8

* Names approved by International Union of Chemistry.