PHYSICAL PROPERTIES OF ORGANIC COMPOUNDS Mr. Maywan Hariono

Objective Learning  To understand the physical properties of organic compounds such as solubility, melting point, refractive index and boiling point of organic compounds  To understand the acid base properties of organic compounds in order to integrate with Henderson-Hesselbach concept.

Solubility of Organic Compounds in Lipid and Water  Why pharmacist assistant should be able to identify the solubility of organic compounds in several solvents???  Please think what you have learned in Basic Formulation & Introduction to Pharmaceutics Subject. - When you prepared Paracetamol Syrup, why you have to dissolve the chemical in alcohol & propylenglicol firstly before you top up with water?

When you studied about Pharmaceutical Dosage Form why some drug can be prepared in syrup while the other ones should be prepared in emulsion or suspension? -When you studied about Introduction to Bioavailability, why some drug has a good absorption while the other ones have a poor absorption so that ones will effect in”onset”, still remember?

 The solubility of an organic compound can provide evidence for the presence (or lack) of several important functional groups, as indicated in the following chart Solvent Some solubility or complete miscibility water Alcohols, amines, acids, esters, ketones, aldehydes (typically only those with C < 4) 5% NaHCO 3 Carboxilic acids 5% NaOH Carboxilic acids and phenols 5% HCl Amines Diethyl ether Most organic molecules

 Most of organic molecules are usually soluble in organic solvents (e.g. diethyl ether, dichloromethane, chloroform, petroleum ether, hexanes etc)  However, some organic molecules are also soluble in water. This denotes a rather high ratio of polar group(s) to carbon chain, i.e., a low molecular weight compound containing an –OH, -NH 2, or CO 2 H group, or a larger molecule containing more than one polar group

 Solubility is defined as the maximum mass of a substance that can be dissolved in a fixed mass of a solvent at a given temperature.  A substance will have a different solubility in different solvents depending on polarity of both the substance and the solvent.  Still remember about ” like dissolves like ” ?

Predict the following organic compounds solubility in water, ethanol, benzene

 The presence of an acidic CO 2 H or basic NH 2 group in a water- soluble compound can be detected by low or high pH, respectively, of the solution.  Compounds which are insoluble in water can dissolve to a significant extent in aqueous acid or base if they form an ionic species.  The solubilty of carboxilic acids (K A = to ) and phenols (K A = to ) in aqueous hydroxide is due to the formation of the carboxylate or phenoxide, since they are much stronger acids than water (K A = ) and the acid equilibria lie far to right.

 Carboxylic acids, but phenols, are also stronger than carbonic acid (K A = ) and they are therefore soluble also in NaHCO 3 solution:  The solubility of amines in dilute aqueous acid similarly reflects the fact that they are stronger bases than water, and are converted to ammonium ion

Melting Point 1.Melting point is the temperature range over which the solid melts to become a liquid 2.The transition between the solid and the liquid is so sharp for small samples of pure substance that melting points can be measured to ± 1 o C

 Melting points of pure compounds are recorded in The Handbook of Chemistry and Physics (CRC) or the Merck Index  Measurement of the melting point of solid can also provide information about purity of the substance.  Pure crystalline solids have a sharp melting point whereas mixtures melt with a broad temperature range.

What is the use of melting point property in pharmacy?  For the new compounds which no have observed data, melting point can be used to detect the synthetic product compared to the starting material.  Example: 1stly, aspirin is synthesized by reacting salicylic acid & acetic acid anhydride. How can we ensure that aspirin has been yielded from the reaction?  By measuring of melting point the product & the starting material we can sure that the product has already obtained.  Aspirin (m.p o C) but salicylic acid (m.p o C)

 In drug analysis, we can identify the unknown compound and compare to CRC

Measuring Melting Point  Using electrothermal Melt- point tester

Boiling Points  Likely the melting points, boiling points are a physical properties  The boiling point of liquid is affected by the forces that attract one molecule to another- ionic attraction, dipole-dipole interaction, hydrogen bonding & van der Waals force.

 A very liquid in a very clean vessel will superheat and not boil when subjected to a temperature above its boiling point  If boiling does occur under these conditions, it occurs with explosive violence.

Application in Pharmacy  Such as melting point, boiling point can be used to identify the unknown drugs.  We can refer to CRC to compare the observed boiling point data with the data from literature  The difference in boiling point informs the difference in molecule structure

 Phenol is an antiseptic that has boiling point higher than ether that was used as general anesthetic.  Why is b.p of phenol higher than ether?

 propylenglicol is an adjunct (co-solvent) has a boiling point higher than

Refractive index  The refractive index (or index of refraction) of a medium is a measure of how much the speed of light (or other waves such as sound waves) is reduced inside the medium. refraction  Since refractive index is a fundamental physical property of a substance, it is often used to identify a particular substance, confirm its purity, or measure its concentration.

Measuring refractive index ethanol acetone Ethyl acetate refractometer

Density  The density of a material is defined as its mass per unit volume massvolume massvolume

 Density can be used to examine the unknown sample qualitatively  The measurement can use PICNOMETER

OPTICAL ROTATION

Optical rotation can be used to identify chirality