Idea of Purification of compounds
Almost everything that we see these days is impure, isn’t it? The water we drink and the food we eat also need to go through levels of purification processes. Similar is the case with organic compounds. There are several methods of purification of organic compounds.
Types of Purification
A large number of methods are available for the purification of substances. The choice of method, however, depends upon the nature of substance (whether solid or liquid). It also depends on the type of impurities present in it. We commonly use these methods for purification of substances:
• Simple crystallisation
• Fractional crystallisation
• Sublimation
• Simple distillation
• Distillation under reduced pressure
Simple Crystallisation/ Recrystallisation
This is the most common method that we use to purify organic solids. For crystallisation, a suitable solvent is one
which dissolves more of the substance at a higher temperature than at room temperature in which impurities are either insoluble or dissolve to an extent that they remain in solution (in the mother liquor) upon crystallisation
which is not highly inflammable and
which does not react chemically with the compound to be crystallized. The most commonly-used solvents for crystallisation are water, alcohol, ether, chloroform, carbon- tetrachloride, acetone, benzene, petroleum ether etc.
Recrystallization is a technique used to purify solid compounds. Solids tend to be more soluble in hot liquids than in cold liquids. During recrystallization, an impure solid compound is dissolved in a hot liquid until the solution is saturated, and then the liquid is allowed to cool. The compound should then form relatively pure crystals. Ideally, any impurities that are present will remain in the solution and will not be incorporated into the growing crystals (Figure 1). The crystals can then be removed from the solution by filtration. Not all of the compound is recoverable — some will remain in the solution and will be lost.
Recrystallization is not generally thought of as a separation technique; rather, it is a purification technique in which a small amount of an impurity is removed from a compound. However, if the solubility properties of two compounds are sufficiently different, recrystallization can be used to separate them, even if they are present in nearly equal amounts. Recrystallization works best when most impurities have already been removed by another method, such as extraction or column chromatography.
Figure 1. The general scheme for recrystallization.
PRINCIPLES
A successful recrystallization depends on the proper choice of solvent. The compound must be soluble in the hot solvent and insoluble in the same solvent when it is cold. For the purpose of recrystallization, consider 3% w/v the dividing line between soluble and insoluble: if 3 g of a compound dissolves in 100 mL of a solvent, it is considered soluble. In choosing a solvent, the bigger the difference between hot solubility and cold solubility, the more product recoverable from recrystallization.
The rate of cooling determines the size and quality of the crystals: rapid cooling favors small crystals, and slow cooling favors the growth of large and generally purer crystals. The rate of recrystallization is usually greatest at about 50 °C below the melting point of the substance; the maximum formation of crystals occurs at about 100 °C below the melting point.
Although the terms "crystallization" and "recrystallization" are sometimes used interchangeably, they technically refer to different processes. Crystallization refers to the formation of a new, insoluble product by a chemical reaction; this product then precipitates out of the reaction solution as an amorphous solid containing many trapped impurities. Recrystallization does not involve a chemical reaction; the crude product is simply dissolved into solution, and then the conditions are changed to allow crystals to re-form. Recrystallization produces a more pure final product. For this reason, experimental procedures that produce a solid product by crystallization normally include a final recrystallization step to give the pure compound.
PROCEDURE
Perform all steps in a fume hood to prevent exposure to solvent fumes.
1. Selecting a Solvent
1. Place 50 mg of the sample (N-bromosuccinimide) in an Erlenmeyer flask. 2. Add 0.5 mL of boiling solvent (water). If the sample dissolves completely, the solubility in the cold solvent is too high to be a good recrystallization solvent. 3. If the sample does not dissolve in the cold solvent, heat the test tube until the solvent boils. 1. If the sample has not completely dissolved at this point, add more boiling solvent drop-wise, until all of the solid dissolves. If it takes more than 3 mL to dissolve the sample in the hot solvent, the solubility in this solvent is probably too low to make it a good recrystallization solvent. 4. If the first choice of solvent is not a good recrystallization solvent, try others. If a single solvent that works cannot be found, try a two solvent system. 1. If you cannot find a suitable single solvent system, then a solvent pair may be necessary. When identifying a solvent pair, there are several key considerations 1) The first solvent should readily dissolve the solid. 2) The second solvent must be miscible with the 1st solvent, but have a much lower solubility for the solute. 2. As a general rule "likes dissolve likes" meaning that polar compounds tend to be soluble in polar solvents and non-polar compounds are often more soluble non-polar compounds. 3. Common solvent pairs (Table 1) 5. Make sure the solvent has a boiling point of at least 40 °C, so there is a reasonable temperature difference between boiling solvent and room-temperature solvent. 6. Ensure that the solvent has a boiling point below about 120 °C, so it's easier to remove the last traces of solvent from the crystals. 7. Also make sure the boiling point of the solvent is lower than the melting point of the compound, so the compound forms as solid crystals rather than as an insoluble oil. 8. Confirm that the impurities are either insoluble in the hot solvent (so they can be hot-filtered out, once the compound is dissolved) or soluble in the cold solvent (so they stay dissolved during the entire process).
2. Dissolving the Sample in Hot Solvent
1. Place the compound to be recrystallized in an Erlenmeyer flask. This is a better choice than a beaker, since the sloping sides help trap solvent vapors and slow the rate of evaporation. 2. Place the solvent (water) in a separate Erlenmeyer flask, and add boiling chips or a stir bar to keep it boiling smoothly. Heat it to boiling on a hotplate. 3. Add hot solvent to a flask at room temperature containing the compound in small portions, swirling after each addition, until the compound is completely dissolved. 1. During the dissolution process, keep the solution hot at all times by resting it on the hotplate, too. Do not add more hot solvent than necessary - just enough to dissolve the sample. 4. If a portion of the solid does not seem to dissolve, even after more hot solvent has been added, it is likely due to the presence of very insoluble impurities. If this happens, stop adding solvent and do a hot filtration before proceeding. 1. To perform a hot filtration, fold a piece of filter paper into a fluted cone shape and place it into a glass stemless funnel. 2. Add a 10-20% excess of hot solvent to the hot solution to allow for evaporation in the procedure. 3. Pour the solution through the paper. If crystals begin to form at any time during the process, add a small portion of warm solvent to dissolve them.
3. Cooling the Solution
1. Set the flask containing the dissolved compound on a surface that does not conduct the heat away too quickly, such as a paper towel set on a benchtop. 2. Lightly cover the flask as it cools to prevent evaporation and to prevent dust from falling into the solution. 3. Leave the flask undisturbed until it cools to room temperature. 4. Once the crystals have formed, place the solution in an ice bath to ensure that the maximum amount of crystals is obtained. The solutions should be left undisturbed in the ice bath for 30 min to 1 h, or till the compound appears to have completely crystalized out of solution. 5. If no crystal formation is evident, it can be induced by scratching the inside walls of the flask with a glass rod or by adding a small seed crystal of the same compound. 1. If this still fails to work, then too much solvent was probably used. Reheat the solution, allow some of the solvent to boil off, then cool it.
4. Isolating and Drying the Crystals
1. Set the cold flask containing the newly formed crystals on a benchtop. 2. Lightly cover the flask to prevent evaporation and to prevent dust from falling into the solution. 3. Isolate the crystals by vacuum filtration, using either a Büchner or Hirsch funnel (clamp the flask to a ring stand first). 4. Rinse the crystals on the Büchner funnel with a small amount of fresh, cold solvent (the same solvent used for recrystallization) to remove any impurities that may be sticking to the crystals. 5. To dry the crystals, leave them in the filter funnel and draw air through them for several minutes. Crystals can also be air-dried by allowing them to stand uncovered for several hours or days. More efficient methods include vacuum drying or placing in a desiccator. Polar Solvent Less Polar Solvent Ethyl acetate Hexane Methanol Methylene chloride Water Ethanol Toluene Hexane
Table 1. Common solvent pairs.
RESULTS
An example of the results of recrystallization is shown in Figure 2. The yellow impurities present in the crude compound have been removed, and the pure product is left as an off-white solid. The purity of the recrystallized compound can now be verified by nuclear magnetic resonance (NMR) spectroscopy or, if it is a compound with a published melting point, by how similar its melting point is to the literature melting point. If necessary, multiple recrystallizations can be performed until the purity is acceptably high.
Figure 2. 2a) A crude compound (left), 2b) recrystallized product before filtration (middle), and 2c) the same compound after recrystallization (right). APPLICATIONS AND SUMMARY
Recrystallization is a method of purifying a compound by removing any impurities that might be mixed with it. It works best when the compound is very soluble in a hot solvent, but very insoluble in the cold version of the same solvent. The compound must be a solid at room temperature. Recrystallization is often used as a final clean-up step, after other methods (such as extraction or column chromatography) that are effective at removing larger amounts of impurities, but that do not raise the purity of the final compound to a sufficiently high level.
Recrystallization is the only technique that can produce absolutely pure, perfect single crystals of a compound. These crystals can be used for X-ray analysis, which is the ultimate authority in determining the structure and three-dimensional shape of a molecule. In these cases, the recrystallization is allowed to proceed very slowly, over the course of weeks to months, to allow the crystal lattice to form without the inclusion of any impurities. Special glassware is needed to allow the solvent to evaporate as slowly as possible during this time, or to allow the solvent to very slowly mix with another solvent in which the compound is insoluble (called antisolvent addition).
The pharmaceutical industry also makes heavy use of recrystallization, since it is a means of purification more easily scaled up than column chromatography.3 The importance of recrystallization in industrial applications has triggered educators to emphasize recrystallization in the laboratory curriculum.4 For example, the drug Stavudine, which is used to reduce the effects of HIV, is typically isolated by crystallization.5 Often, molecules have multiple different crystal structures available, so it is necessary for research to evaluate and understand which crystal form is isolated under what conditions, such as cooling rate, solvent composition, and so forth. These different crystal forms might have different biological properties or be absorbed into the body at different rates. A more common use of recrystallization is in making rock candy. Rock candy is made by dissolving sugar in hot water to the point of saturation. Wooden sticks are placed into the solution and the solution is allowed to cool and evaporate slowly. After several days, large crystals of sugar have grown all over the wooden sticks.
Sugar having an impurity of common salt can be crystallized from hot ethanol since sugar dissolves in hot ethanol but common salt does not.
A mixture of benzoic acid and naphthalene can be separated from hot water in which benzoic acid dissolves but naphthalene does not.
Fractional Crystallisation
It is the process of separation of different components of a mixture by repeated crystallisations. In the first step, we dissolve the mixture in a solvent in which the two components have different solubilities. When we cool a hot saturated solution of this mixture, the less soluble component crystallises out first while the more soluble substance remains in solution.
The mother liquor left after crystallisation of the less soluble component is again concentrated and then we allow it to cool. Hence, we obtain the crystals of the more soluble component.
Sublimation
Certain organic solids on heating directly change from solid to vapour state without passing through a liquid state. These substances are sublimable. This process is sublimation.
We use this process for the separation of sublimable volatile compounds from non-sublimable impurities. We use this for the purposes of purification of camphor, naphthalene, anthracene, benzoic acid, Iodine and salicylic acid etc containing non-volatile impurities.
Simple Distillation
Distillation is the joint process of vapourisation and condensation. We use this method for the purification of liquids which boil without decomposition and contain non-volatile impurities. We can also use this method for separating liquids having sufficient difference in their boiling points.
Fractional Distillation
We can use this process to separate a mixture of two or more miscible liquids which have boiling points close to each other. We carry out this process by using fractionating columns. The fractionating column is a special type of long glass tube that has obstructions to the passage of the vapour upwards and that of liquid downwards. This method can separate a mixture of acetone (b. p. 330 K) and methyl alcohol (b. p. 338 K) or a mixture of benzene and toluene.
Distillation under Reduced Pressure We use this method for the purification of high boiling liquids and liquids which decompose at or below their boiling points. Practical examples include the crude oil industry, sugarcane industry etc.
Steam Distillation
This method is applicable for the separation and purification of those organic compounds (solids or liquids) which:
• are insoluble in water
• are volatile in steam
• possess a high vapour pressure (10-15 mm Hg) at 373 K and
• contain non-volatile impurities.
Azeotropic Distillation
An azeotropic mixture is a mixture having a constant boiling point. The most familiar example is a mixture of ethanol and water in the ratio of 95.87: 4.13 (a ratio present in rectified spirit). It boils at 78.13oC. We can’t separate the constituents of an azeotropic mixture by fractional distillation. Hence, we have to use a special type of distillation (azeotropic distillation) for separating the constituents of an azeotropic mixture.
In this method, we use the third compound in distillation. The process uses the fact that dehydrating agents like diethyl ether etc. depress the partial pressure of one of the original components. As a result, the boiling point of that component raises sufficiently and thus, the other component will distil over.
Chromatography
This is a modern method that we can use for the separation of mixtures into its components, purification of compounds and also test the purity of compounds. The name chromatography comes from the Greek word ‘chroma’ meaning colour and ‘graphy’ for writing because the method was first used for the separation of coloured substances found in plants. This method was described by Tswett in 1906.
Principle of Chromatography
The technique of chromatography uses the difference in the rates at which the components of a mixture move through a porous medium (stationary phase) under the influence of some solvent or gas (moving phase).
Thus, this technique consists of two phases- one is a stationary phase of the large surface area while the second is a moving phase which is allowed to move slowly over the stationary phase. The stationary phase is either a solid or a liquid while the moving phase may be a liquid or a gas. There are also some other methods of purification like differential extraction and other chemical methods.
Fractional Crystallisation
A single crystallisation operation performed on a solution or a melt may fail to produce a pure crystalline product for a variety of reasons including: (a) the impurity may have solubility characteristics similar to those of the desired pure component, and both substances consequently co-crystallise, (b) the impurity may be present in such large amounts that the crystals inevitably become contaminated. (c) a pure substance cannot be produced in a single crystallisation stage if the impurity and the required substance form a solid solution. Fractional crystallisation and recrystallisation from a solution or a melt is, therefore, widely employed to increase crystal purity.
Definition: The stepwise crystallisation of two or more different substances induced by changes in concentration or temperature. The sample is mixed with a solvent, heated, and then gradually cooled so that, as each of its constituent components crystallises, it can be removed in its pure form from the solution.
In chemistry, fractional crystallization is a method of refining substances based on differences in their solubility. It is the process of separation of different components of a mixture by repeated crystallisations. It fractionates via differences in crystallization (forming of crystals). If a mixture of two or more substances in solution are allowed to crystallize, for example by allowing the temperature of the solution to decrease or increase, the precipitate will contain more of the least soluble substance. The proportion of components in the precipitate will depend on their solubility products. In the first step, we dissolve the mixture in a solvent in which the two components have different solubilities. When we cool a hot saturated solution of this mixture, less soluble component crystallises out first while the more soluble substance remains in solution.The mother liquor left after crystallisation of the less soluble component is again concentrated and then allowed to cool. Hence, we obtain the crystals of the more soluble component. If the solubility products are very similar, a cascade process will be needed to effectuate a complete separation. This technique is often used in chemical engineering to obtain very pure substances, or to recover saleable products from waste solutions. Fractional crystallization can be used to separate solid-solid mixtures. An example is separating KNO3 and KClO3.
Application of Fractional Crystallisation Ques :- Explain how fractional crystallisation may be applied to a mixture of sodium chloride and sodium nitrate given the following data. At 293 K, the solubility of sodium chloride is 36 kg/100 kg water and of sodium nitrate 88 kg/100 kg water. Whilst at this temperature, a saturated solution comprising both salts will contain 25 kg sodium chloride and 59 kg of sodium nitrate per 100 kg of water. At 373 K, these values, again per 100 kg of water, are 40 and 176 and 17 and 160, respectively.
Solution The data enable a plot of kg NaCl/100 kg of water to be drawn against kg NaNO3/100 kg of wateras shown in Figure. On the diagram, points C and E represent solutions saturated with respect to both NaCl and NaNO3 at 293 K and 373 K respectively. Fractional crystallisation may then be applied to this system as follows: (a) A solution saturated with both NaCl and NaNO3 is made up at 373 K. This is represented by point E, and, on the basis of 100 kg water, this contains 17 kg NaCl and 160 kg NaNO3. (b) The solution is separated from any residual solid and then cooled to 293 K. In so doing, the composition of the solution moves along EG. (c) Point G lies on CB which represents solutions saturated with NaNO3 but not with NaCl. Thus the solution still contains 17 kg NaCl and in addition is saturated with 68 kg NaNO3. That is (168 − 68) = 92 kg of pure NaNO3 crystals have come out of solution and this may be drained and washed.
In this way, relatively pure NaNO3, depending on the choice of conditions and particle size, has been separated from a mixture of NaNO3 and NaCl. The amount of NaNO3 recovered from the saturated solution at 373 K is: (92 × 100)/160 = 57.5%
CRYSTALLISATION If the cycle is then repeated, during the evaporation stage the sodium chloride is precipitated (and removed!) whilst the concentration of the nitrate re-attains 160 kg/100 kg water. On cooling again, the amount of sodium nitrate which crystallises out is 91.7 kg/100 kg water, or: (91.7 × 100)/160 = 57.3 per cent of the nitrate in solution, as before. The same percentage of the chloride will be precipitated on re-evaporation. PURIFICATION BY SUBLIMATION
Some compounds are capable of sublimation, which is the direct phase change from solid to gas. These substances are sublimable. Solid carbon dioxide is an example of a substance that sublimes readily at atmospheric pressure, as a chunk of dry ice will not melt, but will seem to "disappear" as it turns directly into carbon dioxide gas. Sublimation is an analogous process to boiling, as it occurs when a compound's vapor pressure equals its applied pressure (often the atmospheric pressure). The difference is that sublimation involves a solid's vapor pressure instead of a liquid's. Most solids do not have an appreciable vapor pressure at easily accessible temperatures, and for this reason the ability to sublime is uncommon. Compounds that are capable of sublimation tend to be those with weak intermolecular forces in the solid state. These include compounds with symmetrical or spherical structures. Examples of compounds that can be sublimed are in Figure
Compounds that can be vacuum sublimed
The reverse process of sublimation is deposition or desublimation, in which a substance passes directly from a gas to a solid phase. Sublimation has also been used as a generic term to describe a solid-to-gas transition (sublimation) followed by a gas-to-solid transition (deposition).
Sublimation is used by chemists to purify compounds. We use this process for the separation of sublimable volatile compounds from non- sublimable impurities. E.g. purification of camphor, naphthalene, anthracene, benzoic acid, Iodine and salicylic acid etc containing non- volatile impurities.
A solid is typically placed in a sublimation apparatus and heated under vacuum. Under this reduced pressure, the solid volatilizes and condenses as a purified compound on a cooled surface (cold finger), leaving a non-volatile residue of impurities behind. Once heating ceases and the vacuum is removed, the purified compound may be collected from the cooling surface. For even higher purification efficiencies, a temperature gradient is applied, which also allows for the separation of different fractions. Typical setups use an evacuated glass tube that is heated gradually in a controlled manner. The material flow is from the hot end, where the initial material is placed, to the cold end that is connected to a pump stand. By controlling temperatures along the length of the tube, the operator can control the zones of re-condensation, with very volatile compounds being pumped out of the system completely (or caught by a separate cold trap), moderately volatile compounds re-condensing along the tube according to their different volatilities, and non- volatile compounds remaining in the hot end. Vacuum sublimation of this type is also the method of choice for purification of organic compounds for use in the organic electronics industry, where very high purities (often > 99.99%) are needed to satisfy the standards for consumer electronics and other applications.
As relatively few solids are capable of sublimation, the process can be an excellent purification method when a volatile solid is contaminated with non-volatile impurities. The impure solid is heated in the bottom of a vessel in close proximity to a cold surface, called a "cold finger". As the volatile solid sublimes, it is deposited on the surface of the cold finger (where it can later be recovered), and is thus separated from the non-volatile substance left in the vessel. Sublimation is an example of a "green chemistry" technique, as no solvents are used and no waste is generated. The process, however, is not particularly efficient at separating volatile solids from one another.
Figure Diagram of the sublimation process.
Of the solids with appreciable vapor pressures at room temperature, many still require rather high temperatures to actively sublime (when their vapor pressure equals the atmospheric pressure of nearly 760mmHg760mmHg). If these solids are heated to their sublimation points under atmospheric pressure, some will char and decompose during the process. For this reason, it is very common to perform sublimation under a reduced pressure (vacuum sublimation). Analogous to vacuum distillation in which liquid boils when its vapor pressure equals the reduced pressure in the apparatus, in vacuum sublimation solid sublimes when its vapor pressure equals the reduced pressure in the apparatus. In vacuum distillation, reducing the pressure allows for liquids to boil at a lower temperature. Similarly, reducing the pressure in vacuum sublimation allows for solids to sublime at a lower temperature, one which avoids decomposition.
Purification by Distillation
Distillation is a process of separating the component substances from a liquid mixture by selective evaporation and condensation. It is one of the most common laboratory techniques used by chemists for the purification and identification of organic liquids. Because different compounds often have different boiling points, the components will separate from a mixture when the mixture is distilled. Three different methods can be employed for purifying organic compounds. The optimal method to use will depend on the properties of the mixture:
A simple distillation at atmospheric pressure is used when the organic liquid is:
o • Low-boiling ( <150 C in general). Heating organic compounds above this temperature often leads to decomposition and can be problematic.
• Relatively pure (containing no more than 10% liquid contaminants).
• Has a non-volatile component, for example, a solid contaminant such as a polymer.
• Is contaminated by a liquid with a boiling point that differs by at least 70 oC.
A fractional distillation at atmospheric pressure is used when separating mixtures of liquids with boiling points separated by less than 70 oC.
A reduced pressure distillation under vacuum is used when: • The boiling point of the compound (or solvent) is too high (> 150 oC under atmospheric pressure) to distill the compound (or the solvent) without significant decomposition.
• The compound decomposes upon heating at atmospheric pressure.
Distillation is the process of separating the components or substances from a liquid mixture by using selective boiling and condensation. Distillation may result in essentially complete separation (nearly pure components), or it may be a partial separation that increases the concentration of selected components in the mixture. In either case, the process exploits differences in the relative volatility of the mixture's components. In industrial chemistry, distillation is a unit operation of practically universal importance, but it is a physical separation process, not a chemical reaction. Distillation can also be used to separate a solution made of two or more liquids or fractions, they are called miscible liquids and they must have different boiling points, for example, ethanol and water or fermented fruit juice. a condenser is used a mixture is heated to just over 80 degrees Celsius (the boiling point of ethanol is 79 degrees Celsius) the ethanol will evaporate and is condensed. It can be collected in a beaker. The water remains in the flask.
SILVER SALT METHODS
Procedure A known mass of a carboxylic acid is dissolved in ammonium hydroxide. The ammonium salt of the acid is treated with silver nitrate to obtain the silver salt of the acid. The silver salt of the acid is ignited and metallic silver is obtained as residue.
Reaction involved
Calculations
Weight of carboxylic acid = W g
Weight of silver salt of acid = X1 g
Weight of metallic silver = X2 g i.e. X2 g of silver are obtained from X1 g of silver salt
Then 108 g of silver are obtained from = g of silver salt
Thus, molar mass of silver salt of carboxylic acid = g For monocarboxylic acid, molar mass
=
= – 108 + 1
= – 107 For polybasic carboxylic acid of basicity n, molar mass =
= – n(108) + n(1)
=
Molar mass of acid =
CHLOROPLATINATE SALT METHOD
Procedure A known mass of organic base is treated with chloroplatinic acid to form chloroplatinate salt. These salt on heating decompose to give metallic platinum.
Reaction involved
Calculations
Weight of organic base = W g Weight of chloroplatinate salt = X1 g
Weight of metallic platinum = X2 g
i.e. X2 g of platinum are obtained from X1 g of chloroplatinate salt
Then 195 g of platinum are obtained from = g of chloroplatinate salt For monoacid bases, molar mass =
= For polyacid bases of acidity n, molar mass =
=
=
Molar mass of base =
Modern method
The methods described in the above for determination of molecular formula of a compound require a large amount of a sample and also longer time. Nowadays, better methods using only micrograms of sample and shorter time are available. Spectroscopic methods such as ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, mass spectroscopy etc. are used. The molecular weight of a compound is determined by mass spectroscopy. The various functional groups present and hence the molecular and structural formula is determined by infra red and nuclear magnetic resonance spectroscopy.