Organic Chemistry 101: Separation and Purification

It is used to transfer or convert a mixture of substances into at least two distinct products. Compared to the original mixture, one of these products must be enriched in one chemical component and depleted in the others.

In some cases, but not always, a separation may fully divide the mixture into its pure constituents. Separations are classified based on the technique and apparatus as well as the specific chemistry of the mixture.

Separations require differences in chemical properties such as size, shape, mass, intermolecular forces, or chemical affinity between the constituents of a mixture.

If no single difference can be used to accomplish a desired separation, multiple processes can be performed in combination.

It refers to the process of moving a solute from one phase to another for easier separation.

There are many forms of extraction, but the two most common are solid-liquid and liquid-liquid (or aqueous-organic).

It is a special type of liquid-liquid extraction. This is used to separate dissolved compounds based on relative solubility.

A dissolved solution is exposed to an immiscible solvent, resulting in an aqueous layer and an organic layer. One constituent dissolves in the new layer, leaving the remainder in the original solution. Since the two layers are immiscible, they can then be separated, and the dissolved constituent is separately reconstituted through a work-up step.

It is used to separate solid mixtures based on relative solubility in a liquid solvent.

A solid mixture is exposed to a solvent which dissolves at least one constituent and leaves the remainder in the solid phase. The entire mixture can then be filtered, separating out the solid; the dissolved mixture can then be separately reconstituted.

Solid-liquid extraction could be used simply by adding water to the mixture.

The table salt will dissolve, or move into the aqueous phase, while the sand will not. As a solid, the sand can easily be filtered out. The salt can then be recovered through evaporation.

Any compound with similar chemical properties to water will dissolve in it readily (“like dissolves like”). Generally, polar compounds fulfill this requirement.

Specifically, molecules that can hydrogen bond (including ethanol, ammonia, and hydrogen fluoride) are especially water-soluble. Additionally, charged ions (such as Na+ and Cl-), and molecules with a large dipole moment (such as acetone and dimethylsulfoxide) dissolve in water.

Nonpolar compounds tend to dissolve well in nonpolar solvents. These compounds, which do not dissolve in water, are considered hydrophobic or lipophilic.

Specifically, hydrocarbons (such as cyclohexane and benzene), ethers, and very large aldehydes and ketones fit into this category.

It helps precisely separate the aqueous and organic layers.

It is shaped like an inverted water droplet, with a valve called a stopcock blocking the bottom of the funnel.

When two immiscible liquids are present in the funnel, they settle into two distinct layers. The denser layer, which is located on the bottom, can be poured off by opening the stopcock. The narrow shape of the funnel allows for maximal separation of the layers.

1. Add both water and a suitable organic solvent, such as carbon tetrachloride, to a separatory funnel. The two solvents will separate into immiscible layers.

2. Add the mixture of ethanol and benzene.

3. The ethanol will dissolve in the water, while the benzene will move to the organic layer. These layers can then be physically separated.

4. The ethanol and benzene can be recovered later in a work-up step.

It will contain hexane.
The other layer, which contains water, is known as the aqueous layer.

Extractions generally require both a nonpolar solvent and a polar one. These will form immiscible layers, with the more dense layer at the bottom of the funnel.

The acidic species can be deprotonated by the addition of a base. This causes the molecule to become an anion, moving it to the aqueous layer.

Remember, charged molecules are especially water-soluble.

This is a type of aqueous-organic extraction.

Aqueous acid. This would protonate the basic -NH2 group on phenylamine, moving that molecule to the aqueous layer.

Specifically, protonation results in C6H5NH3+, an ionic species. Such charged molecules will preferentially dissolve in water over ether, a comparatively nonpolar solvent. Benzene will not be protonated, so it will remain in the organic layer.

The basic species can be protonated by the addition of an acid. This causes the molecule to become a cation, moving it to the aqueous layer.

Remember, charged molecules are especially water-soluble.

This is a type of aqueous-organic extraction.

Aqueous base should be added to the mixture. This would deprotonate the -COOH group on benzoic acid, moving that molecule to the aqueous layer.

Specifically, deprotonation results in C6H5COO-, an ionic species. Such charged molecules will preferentially dissolve in water over hexane, a comparatively nonpolar solvent. Benzene will not be deprotonated, so it will remain in the organic layer.

A compound’s boiling point is primarily determined by two properties:

1. The size and branching of the molecule

2. The strength of the intermolecular attractive forces between the molecules

Typically, size trumps intermolecular attractive forces; very large nonpolar compounds have higher boiling points than small polar ones.

Water

Hydrogen bonding, a relatively strong type of intermolecular interaction, tends to increase boiling point. Both of these compounds can hydrogen bond, but water contains two hydroxyl groups compared to the single -OH in ethanol. Water is thus capable of twice as much hydrogen bonding, giving it a higher boiling point.

Water

The -OH groups in water are capable of hydrogen bonding, while the C=O group in acetone only results in dipole-dipole interactions between the molecules. Hydrogen bonding is a stronger type of intermolecular interaction than dipole-dipole forces, and the stronger the attraction between molecules, the higher the boiling point.

Hexane

Higher molecular weight results in a higher boiling point. As a 6-carbon compound, hexane is heavier than propane, a 3-carbon compound.

n-butanol

As isomers, these two molecules are identical in their molecular weights and ability to hydrogen bond. They only differ in their amount of branching; tert-butanol is a highly branched compound, while n-butanol has a straight-chain structure. More branching reduces the surface area available for intermolecular interactions, lowering the boiling point.

Boiling point relates to distillation, which is a separation technique used for mixtures of liquids.

The mixture is heated until the more volatile component boils away.

The boiled vapor is condensed back to its liquid phase in a separate container, resulting in two product solutions that are relatively more pure than before.

The liquids must differ significantly in their boiling points. Simple distillation requires a boiling point difference of at least 25°C.

If the boiling points are too close, boiling will produce vapor with a significant amount of both compounds, which is not an effective separation.

The two liquids can be separated using fractional distillation. This technique is used instead of simple distillation when the components’ boiling points are fairly close.

In fractional distillation, a separation column is added to the distillation apparatus. The column effectively lengthens the distance over which the vapor travels, allowing only the more volatile component to separate off as gas while the less volatile component recondenses.

Yes. The two liquids can be separated if fractional distillation is used.

Only simple distillation requires the liquids to have a relatively large boiling point difference. Fractional distillation is used to separate compounds that are more similar.

Vacuum distillation

By attaching a vacuum pump to the heating portion of the distillation apparatus, the liquids' boiling points can be lowered, allowing distillation to occur at lower temperatures.

Remember that a liquid will boil when its vapor pressure equals the external pressure. Lowering ambient pressure, then, will allow any liquid to boil more easily.

Simple distillation

This technique is ideal here because the boiling point difference between acetone and water is fairly large (about 44°C). Acetone will boil first and can be condensed in a separate flask.

Fractional distillation

This technique is ideal here because the boiling point difference between isoheptane and water is very small (about 10°C). Isoheptane will boil first and can be condensed in a separate flask.

Vacuum distillation

This technique is ideal here because the boiling points are both very high. Under this reduced pressure, both compounds will evaporate more readily. Glycerine will boil first and can be condensed in a separate flask.

Chromatography

Specifically, chromatography is the separation and/or identification of the components of a mixture using their differing affinities for the stationary and mobile phases.

• Stationary phase does not change position relative to the apparatus. Common materials used are silica beads and alumina fibers.

• Mobile phase travels, or flows, through the apparatus. Common solvents used here are water and acetone.

All forms of chromatography consist of a stationary phase and a mobile phase, which must have different properties. The chemical mixture is introduced to this apparatus by spotting or pouring it through.

Compounds within the mixture will have relative affinities towards either the stationary or mobile phase, causing them to move at different rates.

Also known as retention factor, is a measure of the sample's affinity toward the mobile phase.

Rf = dsubstance traveled/dsolvent traveled

Substances with high Rf values have higher affinities for the mobile phase and lower affinities for the stationary phase.

It means that the substance has complete affinity for the mobile phase (or no affinity for the stationary phase). The substance thus moves with the solvent front.

Rf = dsubstance traveled/dsolvent traveled

It means that the substance has complete affinity for the stationary phase (or no affinity for the mobile phase). The substance does not move at all.

Rf = dsubstance traveled/dsolvent traveled

Substance A will move farther than Substance B.

A higher Rf value always indicates a greater affinity for the mobile phase, which allows the compound to move farther.

Rf = dsubstance traveled/dsolvent traveled

Compounds that can be analyzed with gas chromatography (GC) must be sufficiently volatile that they can be vaporized at reasonable temperatures and pressures.

For this reason, GC is not useful for analyzing extremely large molecules or biological ones that would denature during the process.

Compounds that can be analyzed with gas chromatography (GC) must be sufficiently volatile that they can be vaporized at reasonable temperatures and pressures.

For this reason, GC is not useful for analyzing extremely large molecules or biological ones that would denature during the process.

It is an inert nonpolar gas that flows through the flow column.

Vapor that is less polar will have a higher affinity for the mobile phase, causing it to elute through the column more quickly.

It is a polar liquid that coats the inside of the flow column.

Vapor that is more polar will have a higher affinity for the stationary phase, causing it to elute through the column more slowly.

They are either first dissolved in a solvent or already present in a fluid form. They must be able to move across and deposit on the stationary phase, or plate.

As the mobile phase travels along the stationary phase, different sample molecules will move at different rates depending on their polarity.

It is a thin layer covering a solid plate. The thin layer is capable of wicking a liquid upward via capillary action.

The most common stationary phase in TLC is a polar silica layer covering an impermeable ceramic plate, though paper chromatography is also common in labs.

It is a liquid that wicks up the stationary phase via capillary action.

The most common materials used as a mobile phase in TLC are nonpolar organic solvents such as CCl4 or ether.

• It is only used to separate colored substances, while TLC can involve a variety of methods to visualize colorless compounds.

• The stationary phase is a single substance: high-quality filter paper. In TLC, the plate is often composed of a solid with a special stationary phase coating.

In both types of chromatography, the mobile phase is a liquid, though paper chromatography tends to use polar solvents much more often.

It is a separation process used for solid mixtures. Generally, one solid component is our desired product and the rest are impurities.

There are many different types of recrystallization processes, but the most common is single-solvent recrystallization. The compound being purified should be insoluble in that solvent at low temperature and soluble at high temperature.

A solid mixture is introduced to the least amount of a hot solvent necessary to completely dissolve. The solution is then cooled until the point where the pure solid precipitates, or recrystallizes.

Gradual temperature changes (slower recrystallization) tend to result in more pure solids.

Recrystallization

Since this example requires the separation of a solid from other solids, recrystallization is the best technique to use. The acetylsalicylic acid should be dissolved in a heated solvent, then cooled until it solidifies. The recrystallization process tends to exclude most solid impurities.