INTRODUCTION

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Solid compounds synthesized in the Organic laboratory usually need to be purified before final confirmation tests are performed

One of the most commonly used techniques is to purify a sample by dissolving it in a suitable solvent and recrystallizing the pure compound from the saturated solution by slow cooling

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INTRODUCTION The most common method of purifying

solid organic compounds is by recrystallization. In this technique, an impure solid compound is dissolved in a solvent and then allowed to slowly crystallize out as the solution cools. As the compound crystallizes from the solution, the molecules of the other compounds dissolved in solution are excluded from the growing crystal lattice, giving a pure solid.

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Purpose of process Mainly for the purification of solid

crystalline compounds. Melting point is one of the ways of

determining the purity of the compound.

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PRINCIPLES OF RECRYSTALLLIZATION

• Based on difference between the solubilities of the pure substance and impurities in the solvent or mixture of solvents

• 2 different situations could arise• Either the impurities have greater solubility in the

solvent than the pure substance being recrystallized• In which case the impurities will be retained in the

mother liquor and several recrystallizations will yield the pure substance

• Or the impurities will have less solubility in the solvent than the substance being recrystallized in which case the impurities will not dissolve and more crystals will be obtained

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PRINCIPLES OF RECYSTALLIZATION

At normal laboratory temperatures the substance being recrystallized is not soluble. However ,increasing the temperature results in increased solubility of the pure substance

At/near the boiling point of the solvent, maximum solubility is obtained.

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Solubility of salicylic acid in water

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PRINCIPLES OF RECRYSTALLIZATION

After reaching the boiling point, reduction of temperature results in precipitation of crystal nuclei

Presence of crystal nuclei promotes crystal growth which continues until the temperature is stabilized at the normal laboratory temperature

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PRINCIPLES OF RECRYSTALLIZATION

Assumptions made are: The impurities are present in

comparatively small quantities i.e. less than 5%.

The effect of either component (i.e. the impurity and the pure substance) on the solubility of the other is neglected.

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PROCEDURE There are different types of

recrystallzation techniques, namely Single-solvent recrystallization Multi-solvent recrystallization Hot filtration-recrystallization

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MATERIALS/APPARATUS Fluted filter paper Conical flask Bunsen burner Appropriate solvents Funnel Suction filter Test materials Measuring cylinder

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Procedure(cont.) Summary of Single-solvent

Recrystallization Steps Add a small quantity of appropriate

solvent to an impure solid. Apply heat to dissolve the solid. Cool the solution to crystallize the

product. Use vacuum filtration to isolate and dry

the purified solid.

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Addition of solvent Choose a solvent such that the impure

compound has poor solubility at low temperatures, yet is completely soluble at higher temperatures. The point is to fully dissolve the impure substance when it is heated, yet have it crash out of solution upon cooling. Add as small a quantity as possible to fully dissolve the sample. It's better to add too little solvent than too much. More solvent can be added during the heating process, if necessary.

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Heating the suspension After the solvent has been added to the

impure solid, heat the suspension to fully dissolve the sample. Usually a hot water bath or steam bath is used, since these are gentle, controlled heat sources. A hot plate or gas burner is used in some situations

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Cooling the solution Once the sample is dissolved, the solution is cooled to force

crystallization of the desired compound. Slower cooling may lead to a higher purity product, so it's

common practice to allow the solution to cool to room temperature before setting the flask in an ice bath or refrigerator.

Crystals usually begin forming on the bottom of the flask. It's possible to aid crystallization by scratching the flask with a glass rod at the air-solvent junction (assuming you are willing to purposely scratch your glassware). The scratch increases the glass surface area, providing a roughened surface on which the solid can crystallize. Another technique is to 'seed' the solution by adding a small crystal of the desired pure solid to the cooled solution. Be sure the solution is cool, or else the crystal could dissolve. If no crystals fall out of solution, it's possible too much solvent was used. Allow some of the solvent to evaporate. If crystals do not spontaneously form, reheat/cool the solution.

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FILTER AND DRY THE PRODUCT

Crystals of purified solid are isolated by filtration. This is usually done with vacuum filtration, sometimes washing the purified solid with chilled solvent. If you wash the product, be sure the solvent is cold, or else you run the risk of dissolving some of the sample.

The product may now be dried. Aspiring the product via vacuum filtration should remove much of the solvent. Open-air drying may be used as well. In some cases, the recrystallization may be repeated to further purify the sample.

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This purification technique results in the inevitable loss of the part of "compound A" that remains in solution. A yield of 80% would be considered quite good. However the impure solution can be concentrated and the procedure repeated to gather a "second crop" of crystals.

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MELTING POINT DETERMINATION

The level of purity can then be checked by taking a melting point range of the solid and comparing it to an accepted melting point range if one exists. Compounds that are more pure have higher melting points and melt over a narrower temperature range. Obviously other analytical techniques can be used to assess compound purity such as NMR spectroscopy and elemental analysis.

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PRECAUTIONS The mixture is warmed slowly to facilitate

the crystallization process. The solution is allowed to cool naturally

to room temperature to aid the formation of fine crystals.

The filter paper should adhere over the perforated plate the suction filter.

The filter paper must be moistened before filtration with the chosen solvent.

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PRECAUTIONS(cont) Suction filtration should be done gently. Excess addition of solvent should be

avoided. When two solvents A and B are used for a

Multi-solvent recrystallization process, solvents A and B must be miscible.

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CHOICE OF SOLVENT Substance should be insoluble in solvent

at room temperature but soluble at elevated temperatures.

Impurities should be either soluble or completely insoluble in solvent.

Should yield well defined crystals of required compound.

Should possess low boiling point.

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CHOICE OF SOLVENT(cont) It should not react with the compound of

interests. Should have similar chemical properties

as the compound to be recrystallized. Other factors to be considered include

ease of manipulation, flammability and cost.

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MODERN ADVANCEMENTS It has been proven that under conditions of

microgravity better protein crystals can be obtained. This is due to the fact that under these conditions, movement induced by concentration gradient is almost eliminated.

Furthermore, a recent development has been the use of a Craig tube in ultra micro scale recrystallization

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Craig tubeCraig tubes are particularly useful for recrystallizing amounts of solid less than ~100 mg, the main advantage being that it minimizes the number of transfers of solid material and thus maximizes the yield of crystals. The separation of the crystals from the mother liquor with the Craig tube is very efficient, and little time is required for drying the crystals.

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X-RAY DIFFRACTOMETER

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NMR SPECTROMETERHWB-NMRv900

APPLICATION OF RECRYSTALLIZATION

Generally, recrystallization in pharmacy is used for purification of pharmaceutical formulations .

Chemicals and reagents used for pharmaceutical processes must be achieved in their unadulterated states as much as possible. And this can be acquired by many techniques such as filtration, fractional distillation as well as the normal distillation.

Sometimes these processes may not be enough for the purification of several preparations and therefore the recrystallization process is employed.

Chemicals and reagents used for pharmaceutical processes must be achieved in their unadulterated states as much as possible. And this can be acquired by many techniques such as filtration, fractional distillation as well as the normal distillation.

Sometimes these processes may not be enough for the purification of several preparations and therefore the recrystallization process is employed.

Method for purifying adipic acid by recrystallization

Adipic acid is one of the two base materials for preparing Nylon 6-6. For the applications of Nylon 6-6 it is necessary to have a very high purity, and this purity must exist already at the stage of the precursors, especially at the adipic acid stage.

The direct oxidation of cyclohexane to adipic acid is generally carried out in the presence of cobalt. The adipic acid obtained contains traces of cobalt catalyst.

The present invention consists in an improved process for crystallization or recrystallization of adipic acid, characterized in that the said crystallization or recrystallization is carried out in at least one carboxylic acid having a melting point of less than 20° C.The carboxylic acids employed in the present process are, more particularly, aliphatic carboxylic acids which are saturated or which contain an ethylenic unsaturation.

• Acetic acid and pentenoic acids are preferred, acetic acid owing to its availability and to its use in the synthesis of adipic acid from cyclohexane, and pentenoic acids because they are an intermediate in the preparation of adipic acid from butadiene.The purity of the adipic acid recrystallized in this way may be improved further when recrystallization is carried out in the presence of carbon monoxide.

• The carbon monoxide can make up at least part of the atmosphere above the solution in the crystallization or recrystallization reactor (or reactor headspace) or can create within the said reactor a pressure which is greater than the atmospheric pressure.

In practice, the process will therefore be operated under an absolute pressure of from 0 bar (preferably at least 0.5 bar) to 50 bars of carbon monoxide, the upper limit not being critical in nature but being representative of industrial apparatus which is not excessively expensive.

• The crude adipic acid subjected to recrystallization according to the present process is usually an adipic acid which has already undergone one or more purification treatments, in particular by crystallization from water, by refining or else by distillation, to give it a minimum purity of approximately 95%.

Generally, the adipic acid recrystallized by the process of the invention has a purity of from 95 to 99.95%.

• The recrystallization consists in taking the adipic acid to be purified and dissolving it in the minimum amount of hot aliphatic carboxylic acid, i.e. usually at a temperature from 80 to 250° C., optionally under an at least partial pressure or atmosphere of carbon monoxide, and then inducing crystallization of the dissolved adipic acid by cooling the solution, optionally after having seeded the solution using crystals ofpure adipic acid.

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THE END.