Separation of Mixtures The
identification of the compounds of a mixture involves, first, a separation into individual components and, second, the characterization of each of those components.
It
is very rarely possible to identify the constituents of a mixture without separation.
The
separation of the compounds in a mixture should be as nearly quantitative as possible in order to give some idea of the actual percentage of each component.
Also,
it is very important to carry out the separation in such a manner that each compound is obtained in a pure form.
The
method of separation chosen should be such that the compounds are obtained as they existed in the original mixture. 1
Derivatives of the original compounds are not very useful unless they may be readily reconverted into the original compounds.
In selecting and performing a separation procedure, one should be concerned with: 1. Will the sample survive the separation procedure? That is, are the components of the mixture stable under the conditions of the procedure? 2. Is this the easiest and most efficient way to carry out the separation?
Stability of the sample under the conditions of the separation procedure may not be known until the separation is attempted. 2
Derivatives of the original compounds are not very useful unless they may be readily reconverted into the original compounds.
In selecting and performing a separation procedure, one should be concerned with: 1. Will the sample survive the separation procedure? That is, are the components of the mixture stable under the conditions of the procedure? 2. Is this the easiest and most efficient way to carry out the separation?
Stability of the sample under the conditions of the separation procedure may not be known until the separation is attempted. 2
Compounds which are thermally unstable to the heat required for distillation at atmospheric pressure should be distilled at reduced pressure.
Extractions and column chromatography do not involve heat and thus may be appropriate for samples which cannot be distilled.
However, some samples decompose because of chemical reactions with acid or base in extractions or with chromatographic packing or support in column chromatography.
A
TLC test is a fast and useful check for sample durability under chromatographic conditions.
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Preliminary Examination of Mixtures 1. Note the physical state.
Take advantage of existing separations. If a solid is suspended in a liquid, remove the solid by filtration and examine it separately. If two immiscible liquids are present, separate them and examine them separately.
2. Determine the solubility of the mixture in water.
Classify the mixture according to Figure 5.1 and Table 5.1.
3. With liquid liquid mixtures, mixtures, evapor evaporate ate 2 mL mL of the solution solution to dryness on a glass or porcelain crucible cover and not the presence or absence of a residue. 4
Apply the the ignition ignition test to the the residue or 0.1 0.1 g of the liquid liquid or solid.
4. In liquid samples, determine the presence of water by (a) determining the miscibility of the solution with ether, (b) using the anhydrous copper sulfate test, or (c) using the distillation test for water
Copper sulfate test: add a small sample of anhydrous CuSO4 to the liquid. If the solution turns blue, it is indicative of the presence of water; indicating the copper sulfate has absorbed the water.
The distillation test is more reliable, and is carried out by placing 5 mL of the liquid and 5 mL of anhydrous toluene in the distilling flask of a distillation apparatus. Heat the mixture gently with a flame until distillation occurs. Collect 2 mL of the distillate. Add 5 mL of toluene to the distillate. The presence of two layers or distinct drops suspended in toluene indicates the presence of water. If the solution is 5only cloudy, traces of water are indicated.
5. If water is absent,
Determine the presence of a volatile solvent by placing 1.0 mL of the mixture in a distilling flask in a simple distillation apparatus. Place the distilling flask in a beaker of water and heat the water to boiling. Any liquid that distills under these conditions is classified as a volatile solvent. Examine the distillate, which may be a mixture of readily volatile compounds, and the residue in the flask separately.
It frequently happens that distillation of a water soluble mixture yields a volatile solvent and a water-insoluble residue. The separation of such a mixture is therefore carried out by removing all of the volatile solvent. The residue is then treated as a water insoluble mixture.
If the residue after distillation is a water-soluble liquid, it is best not to remove the solvent at this stage because the separation is usually not quantitative.
If, however, the residue after distillation is a water-insoluble solid and the removal of the solvent seems quantitative, then remove all of the volatile solvent and examine the distillate and the residue separately.
If water is present, no such separation should be attempted. 6
6. Determine the reaction of aqueous solution or suspension of the mixture to litmus and phenolphthalein.
If the mixture is distinctly acidic, titrate I mL (of a known exact weight) of the solution in 2.5 mL of water or ethanol with a standardized 0.1 M sodium hydroxide solution to determine whether considerable amounts of free acid are present or whether the acidity is due to traces of acids formed by hydrolysis of esters.
Perform the titration in an ice-cold solution, and take the first pink color of phenolphthalein as the end point.
Obtain an IR spectrum of a mixture to reveal the presence of several carboxylic acid groups.
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7. Acidify 2 mL of the mixture with 5% hydrochloric acid, and cool the solution. Note the evolution of a gas or the formation of a precipitate. Add 5% sodium hydroxide solution to the solution until the solution is basic and note the result. 8. Make 2 mL of the mixture basic with 5% sodium hydroxide solution. Note the separation of an oil or solid, the liberation of ammonia, and/or any color change. Heat the solution just to boiling and then cool. Compare the odor with that of the original mixture. The presence of esters is often indicated by a change in odor. Next, add 5% hydrochloric acid until the solution is acidic and note the result. 8
9. In the case of water-insoluble mixture, perform an elemental analysis. If water or a large amount of a volatile solvent is present in a water-insoluble mixture, omit the elemental analysis of the mixture. If the water-soluble mixture is composed of solids, perform an elemental analysis. 10. If water is absent, cautiously determine the effect of the following classification reagents: (a) metallic sodium; (b) acetyl chloride 11. Determine the action of the following classification reagents on an aqueous solution or suspension of the original mixture: (a) bromine water; (b) potassium permanganate solution; (c) ferric chloride solution; (d) alcoholic silver nitrate solution; (e) Fuchsin-aldehyde reagent; and (f) 2,4-dinitrophenylhydrazine. 9
Distillation
The short-path process allows distillation of materials such as lowmelting solids for which long exposure to elevated temperatures could be damaging.
10
A microscale distillation apparatus can be used to distill 0.5-2.0 mL of a sample.
In
order to improve the efficiency of a distillation, a column can be placed between the vessel to be heated and the condenser tube.
Frequently,
the column is a condenser filled with glass beads or steel wool to provide increased surface area and/or increase cooling surfaces.
This
vertical is not surrounded by a jacket of water as typically favored in the traditional condenser. 11
Consider a 50:50 mixture of cyclohexane (BP = 78oC) and toluene (BP = 111oC) Question: can cyclohexane be separated by heating the mixture to 78oC?
In
a mixture of cyclohexane and toluene, the vapor above it is not 100% cyclohexane!
Roults law:
vapor pressure of cyclohexane is 0 equal to the product of the vapor pressure of Pc = Pc N c 0 pure cyclohexane and the mole fraction of Pt = Pt N t cyclohexane in the liquid mixture.
The
total vapor pressure above the solution, P Tot, is given by the sum of the partial
PTot = Pc
pressures due to the cyclohexane and toluene. 12
+ Pt
Dalton’s
law states that the mole fraction of cyclohexane in the vapor at a given temperature is equal to the partial pressure of cyclohexane at that temperature divided by the total pressure.
Xc
=
Pc total vspor pressure
Therefore,
to separate a mixture of cyclohexane and toluene, a series of fractions would be collected and each of these partially redistilled.
If this fractional distillation were done enough times the two components could be separated. 13
Efficiency of column is evaluated according to the height equivalent to a theoretical plate (HETP).
The smaller the HETP, the more plates the column will have and the more efficient it will be.
14
Fractional Distillation
A fractional distillation apparatus uses the vertical column in addition to the condenser.
With this distillation apparatus, compounds with a difference in their boiling points of 5-10 oC or more can be efficiently separated.
15
Frequently, the result of a more efficient distillation apparatus, is that the distilling compound remains on the vertical column for a longer time.
To avoid heat loss, the column should be externally insulated with glass wool, cotton, or aluminum foil.
An important aspect in distillation is the method of heating the distilling pot.
For volatile liquids, a steam bath is used.
Baths containing oils, or other involatile, inert substance can be used; such that liquids provide a very even method of heat application and can be used to higher temperatures (ca. 250-400oC).
Heating mantles attached to Variacs can be used for heating application.
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Steam Distillation Steam
distillation is a technique whereby a compound of relatively low volatility can be purified by co-distilling it with water.
When
a mixture of cyclohexane and toluene is distilled, the boiling point of these two miscible liquids is between the boiling points of each of pure components. contrast, if a mixture of benzene (bp 80.1oC) and water (bp 100oC) (immiscible liquids) is distilled, the boiling point of the mixture will be below the boiling point of each pure component.
By
This
distillation occurs because both of the liquid components contribute to the vapor pressure independently (as if it were alone), and when the sum of the partial pressures equals the external pressure, boiling occurs.
Thus,
the distillation can be carried out at a temperature slightly less than 100oC at 760 mmHg. 17
Alternatively, the substance can be heated with water in a simple distillation flask – and the steam is generated in situ.
Some high-boiling substances decompose before the boiling point is reached, and if impure cannot be purified by ordinary distillation. However, with steam distillation they can be 18 purified at a lower temperature.
Rotary Evaporator
A rotary evaporator “rotovap” is useful for solvent removal. The vacuum lowers the boiling point of the liquid. The distilling flask is spun to increase the surface area, to increase the rate of evaporation, and to prevent bumping of the solution.
The solvent is distilled into the receiver, leaving the product in the 19 distilling flask.
A hot-water serves as a source of heat.
Sublimation
Sublimation is a technique in which a solid is heated and vaporized, without passing through the liquid phase. The gas is then condensed and collected as a solid.
Successful sublimation of material from the crude mixture will result in the formation of crystals on the bottom outside of the cold finger.
Before attempting sublimation, look up the boiling point to see if the compound sublimes instead of boiling.
The abbreviation “sub” indicates that the compound sublimes instead of 20 boiling.
Extraction
Extraction is one of humankind’s oldest chemical operation.
The preparation of a cup of coffee or tea involves the extraction of flavor and odor components from dried vegetable matter with hot water.
Extraction is used extensively in the isolation and purification of food flavorings, drugs, and perfumes.
Different types of extraction Soxhelet extraction solid/liquid extraction Liquid/liquid extraction Acid/base extraction
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Properties of Extraction Solvents Should readily dissolve the substance to be extracted
Should have a low boiling point so that it can be recovered readily
Should not react with the other solute or the other solvent
Should not be flammable or toxic
Should be relatively inexpensive
Should not be miscible with water (the usual other phase) Several small extractions are more effective than one large-scale extraction (partition coefficient) 22
Extraction: Separation based upon Salt Formation
Acid/base extraction involves carrying out simple acid/base reactions in order to separate strong acids, weak organic acids, neutral organic compounds, and basic organic substances.
Example:
(1) the separation of aniline from toluene
23
(2) Separation of phenol from toluene
(3) Separation of benzaldehyde from toluene In each of these examples, the original base, acid, or aldehyde is easily recovered by decomposition of the salt by familiar methods. 24
If the compounds to be separated are water soluble to any considerable degree, extraction methods usually have little value. Steam distillation, however, can generally be used instead. Example: a mixture of acetic acid and cyclohexanone . O
O O
.
+
O
NaOH
CH3COH
+
CH3CO Na
.
.
with steam distillation, the ketone will be removed in the distillate while the salt, being nonvolatile, remains behind.
O CH3CO Na 25
O +
H3PO4
CH3COH
+ NaH2PO4
Can be distilled with steam
Example: separation
of diethylamine from 1-butanol
Phosphoric acid is added in sufficient amount to neutralize the amine
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The amine is recovered by adding dilute sodium hydroxide solution to the residue and repeating the steam distillation
Can be removed by steam distillation
Another
useful method for establishing a marked difference in the polar character of the components is illustrated by the separation of mixtures of primary amines from tertiary amines. O CH3CCl O
acylation R3N
+
CH3C
NHR'
neutral amide R3N
+ 'RNH2 O R3N
+
C
NHR'
O C
Cl
neutral amide
benzoylation
The amide can be reconverted to the original amine by hydrolysis 27
A general method can be developed for separating acidic compounds differing in acidity. Strong acids form salts when treated with sodium bicarbonate and can be extracted with this reagent.
28
Example:
separating benzoic acid, phenol, aniline, naphthalene in a mixture
29
30
In practice, mixtures fall into two categories, depending on whether they are soluble in water.
I. Extraction of Water Insoluble Mixtures
The following two procedures are applied after the removal of any volatile solvent.
Also for these procedures to work effectively, no component of the mixture can be soluble in water.
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Procedure A: Water Insoluble Mixture
Of course if the mixture does not contain certain types of compounds, then those fractions will not be obtained.
weak acids 32
stronger acids
If an emulsion occurs, add more water and a few crystals of sodium chloride to aid in the separation of the layers.
An emulsion is a suspension of one liquid as droplets in another.
Emulsion, once formed, can be quite stable.
Prevention is the best cure for emulsions – shake gently to avoid emulsions.
If a bit of emulsion forms it may break simply on standing for a sufficient length of time.
Making the aqueous layer highly ionic will help.
Add as much sodium chloride as will dissolve, and shake the mixture gently.
Watch for pressure build up due to heat from hand, from shaking and/or acid/base reactions or foaming when bicarbonate is added to acid.
To have sufficient room for mixing the layers, fill the separatory funnel no more than three-fourth full.
Withdraw the lower layer from the separatory funnel through the stopcock, and pour the upper layer out through the neck. 33
Procedure B: Water Insoluble Mixture
34
(Abbreviated version of Procedure A)
II. Extraction of Water Soluble Mixtures
If all components of the mixture are water soluble, steam distillation is the best method for separation of the components.
However, it might be unsatisfactory if the components of the mixture could undergo reaction with each other or with boiling aqueous acid or alkali during steam distillation.
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Procedure C: Water Soluble Mixture Place 5 mL of the mixture in a 125-mL round-bottom flask for a steam distillation, and get distillate 1 Place the remainder of the solution (Residue 1) in an evaporating dish and remove the water by means of a steam bath
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Procedure D: Water Soluble Mixture Containing Esters
contains acidic compounds
contains acidic compounds
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(contains the amine salt)
Upper layer (contains the neutral compounds) (an alcohol solution of acids)
O C CH3
OH
acetic acid
CH3CH2CH2CH2OH 1-butanol O C CH3
O(CH2)3CH3 butyl acetate
38
Fe2(SO4)3 ferric sulfate
NH+ SO4
-2
NH+
FeSO4 ferrous sulfate
quinolinium sulfate H2SO4 sulfuric acid NH3+ SO4-2 +
CH2
H3N
CH C
O
anilinium sulfate
acrolein HO OH
NO2 HO nitrobenzene
39
glycerol
H
N
quinoline
NH2
aniline
40
