PHYSICAL PROPERTIES OF PHYSICAL PROPERTIES OF ORGANIC COMPOUNDSORGANIC COMPOUNDS

Mr. Maywan HarionoMr. Maywan Hariono

Objective LearningObjective Learning

To understand the physical properties of To understand the physical properties of organic compounds such as solubility, organic compounds such as solubility, melting point, refractive index and boiling melting point, refractive index and boiling point of organic compoundspoint of organic compounds

To understand the acid base properties of To understand the acid base properties of organic compounds in order to integrate with organic compounds in order to integrate with Henderson-Hesselbach concept. Henderson-Hesselbach concept.

Solubility of Organic Compounds in Solubility of Organic Compounds in Lipid and Water Lipid and Water

Why pharmacist assistant should be able to identify the Why pharmacist assistant should be able to identify the solubility of organic compounds in several solvents???solubility of organic compounds in several solvents???

Please think what you have learned in Basic Formulation & Please think what you have learned in Basic Formulation & Introduction to Pharmaceutics Subject.Introduction to Pharmaceutics Subject.- When you prepared Paracetamol Syrup, why you have to - When you prepared Paracetamol Syrup, why you have to dissolve the chemical in alcohol & propylenglicol firstly dissolve the chemical in alcohol & propylenglicol firstly before you top up with water?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 The solubility of an organic compound can provide evidence for the presence (or lack) of several important evidence for the presence (or lack) of several important functional groups, as indicated in the following chartfunctional groups, as indicated in the following chart

SolventSolvent Some solubility or complete Some solubility or complete miscibilitymiscibility

waterwater Alcohols, amines, acids, esters, Alcohols, amines, acids, esters, ketones, aldehydes (typically only ketones, aldehydes (typically only those with C < 4)those with C < 4)

5% NaHCO5% NaHCO33 Carboxilic acidsCarboxilic acids

5% NaOH5% NaOH Carboxilic acids and phenolsCarboxilic acids and phenols

5% HCl5% HCl AminesAmines

Diethyl etherDiethyl ether Most organic moleculesMost organic molecules

Most of organic molecules are usually soluble in organic solvents (e.g. Most of organic molecules are usually soluble in organic solvents (e.g. diethyl ether, dichloromethane, chloroform, petroleum ether, hexanes diethyl ether, dichloromethane, chloroform, petroleum ether, hexanes etc)etc)

However, some organic molecules are also soluble in water. This 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 denotes a rather high ratio of polar group(s) to carbon chain, i.e., a low molecular weight compound containing an –OH, -NHmolecular weight compound containing an –OH, -NH22, or CO, or CO22H group, H group, or a larger molecule containing more than one polar groupor a larger molecule containing more than one polar group

H3CH2C O CH2CH3

diethyl ether

C

H

H

Cl

Cl

dichloromethane

CH3CH2CH2CH2CH2CH3

n-hexane

Solubility is defined as the maximum mass Solubility is defined as the maximum mass of a substance that can be dissolved in a of a substance that can be dissolved in a fixed mass of a solvent at a given fixed mass of a solvent at a given temperature.temperature.

A substance will have a different solubility in A substance will have a different solubility in different solvents depending on polarity of different solvents depending on polarity of both the substance and the solvent.both the substance and the solvent.

Still remember about Still remember about ””like dissolves likelike dissolves like””??

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

The presence of an acidic COThe presence of an acidic CO22H or basic NHH or basic NH22 group in a water- group in a water-soluble compound can be detected by low or high pH, respectively, soluble compound can be detected by low or high pH, respectively, of the solution.of the solution.

Compounds which are insoluble in water can dissolve to a Compounds which are insoluble in water can dissolve to a significant extent in aqueous acid or base if they form an ionic significant extent in aqueous acid or base if they form an ionic species. species.

The solubilty of carboxilic acids (KThe solubilty of carboxilic acids (KAA= 10= 10-3-3 to 10 to 10-5-5) and phenols (K) and phenols (KAA = = 1010-9 -9 to 10to 10-10-10) in aqueous hydroxide is due to the formation of the ) in aqueous hydroxide is due to the formation of the carboxylate or phenoxide, since they are much stronger acids than carboxylate or phenoxide, since they are much stronger acids than water (Kwater (KAA = 10 = 10-7-7) and the acid equilibria lie far to right. ) and the acid equilibria lie far to right.

OH

carboxylic acid

phenol

R C

O

OH + OH- R C

O

O- + H2O

+ OH-

O-

+ H2O

Carboxylic acids, but phenols, are also stronger Carboxylic acids, but phenols, are also stronger than carbonic acid (Kthan carbonic acid (KAA = 10 = 10-7-7) and they are ) and they are

therefore soluble also in NaHCOtherefore soluble also in NaHCO33 solution: solution:

The solubility of amines in dilute aqueous acid The solubility of amines in dilute aqueous acid similarly reflects the fact that they are stronger similarly reflects the fact that they are stronger bases than water, and are converted to bases than water, and are converted to ammonium ionammonium ion

R C

O

OH + HCO3-

R C

O

O- + H2O + CO2

NH2

+ H3O+

NH3+

+ H2O

Melting PointMelting Point

1.1. Melting point is the temperature range Melting point is the temperature range over which the solid melts to become a over which the solid melts to become a liquidliquid

2.2. The transition between the solid and the The transition between the solid and the liquid is so sharp for small samples of pure liquid is so sharp for small samples of pure substance that melting points can be substance that melting points can be measured to ± 1measured to ± 1ooCC

Melting points of pure compounds are Melting points of pure compounds are recorded in The Handbook of Chemistry and recorded in The Handbook of Chemistry and Physics (CRC) or the Merck IndexPhysics (CRC) or the Merck Index

Measurement of the melting point of solid Measurement of the melting point of solid can also provide information about purity of can also provide information about purity of the substance.the substance.

Pure crystalline solids have a sharp melting Pure crystalline solids have a sharp melting point whereas mixtures melt with a broad point whereas mixtures melt with a broad temperature range. temperature range.

What is the use of melting point What is the use of melting point property in pharmacy?property in pharmacy?

For the new compounds which no have observed data, For the new compounds which no have observed data, melting point can be used to detect the synthetic product melting point can be used to detect the synthetic product compared to the starting material.compared to the starting material.

Example: 1stly, aspirin is synthesized by reacting salicylic Example: 1stly, aspirin is synthesized by reacting salicylic acid & acetic acid anhydride. How can we ensure that acid & acetic acid anhydride. How can we ensure that aspirin has been yielded from the reaction?aspirin has been yielded from the reaction?

By measuring of melting point the product & the starting By measuring of melting point the product & the starting material we can sure that the product has already obtained.material we can sure that the product has already obtained.

Aspirin (m.p. 141-144Aspirin (m.p. 141-144ooC) but salicylic acid (m.p. 158.5-C) but salicylic acid (m.p. 158.5-161161ooC)C)

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

C

OH

O

OH

+ HO C

O

O C

O

OH

C

O

O

OH

C

O

CH3

+ CH3 C

O

OH

salycilic acidm.p. 158.5-161oC

aspirinm.p. 141-144oC

Measuring Melting PointMeasuring Melting Point

Using electrothermal Melt-Using electrothermal Melt-point testerpoint tester

Boiling PointsBoiling Points

Likely the melting points, boiling points are a Likely the melting points, boiling points are a physical propertiesphysical properties

The boiling point of liquid is affected by the The boiling point of liquid is affected by the forces that attract one molecule to another-forces that attract one molecule to another-ionic attraction , dipole-dipole interaction, ionic attraction , dipole-dipole interaction, hydrogen bonding & van der Waals force. hydrogen bonding & van der Waals force.

A very liquid in a very clean vessel will A very liquid in a very clean vessel will superheat and not boil when subjected to a superheat and not boil when subjected to a temperature above its boiling pointtemperature above its boiling point

If boiling does occur under these conditions, If boiling does occur under these conditions, it occurs with explosive violence.it occurs with explosive violence.

Application in Pharmacy Application in Pharmacy

Such as melting point, boiling point can be Such as melting point, boiling point can be used to identify the unknown drugs.used to identify the unknown drugs.

We can refer to CRC to compare the We can refer to CRC to compare the observed boiling point data with the data observed boiling point data with the data from literaturefrom literature

The difference in boiling point informs the The difference in boiling point informs the difference in molecule structuredifference in molecule structure

Phenol is an antiseptic that has boiling point Phenol is an antiseptic that has boiling point higher than ether that was used as general higher than ether that was used as general anesthetic. anesthetic.

Why is b.p of phenol higher than ether?Why is b.p of phenol higher than ether?

O

phenol etherH3C

H2C O

H2C CH3

H

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

H3C CH

OH

H2C OH

propylenglycolb.p. 188.2oC

H3CH2C

H2C OH

propanolb.p. 97.1oC

Refractive indexRefractive index

The The refractive indexrefractive index (or (or index of index of refractionrefraction) of a ) of a medium is a measure of how much the speed of medium is a measure of how much the speed of light (or other waves such as sound waves) is light (or other waves such as sound waves) is reduced inside the medium. reduced inside the medium.

Since refractive index is a fundamental physical Since refractive index is a fundamental physical property of a substance, it is often used to identify property of a substance, it is often used to identify a particular substance, confirm its purity, or a particular substance, confirm its purity, or measure its concentration. measure its concentration.

Measuring refractive indexMeasuring refractive index

ethanol

acetone

H3CH2C OH H3C C

O

CH3 H3C C

O

CH2CH3

D. 1.36 (25oC) D. 1.36 (20oC) D. 1.37 (20oC)

Ethyl acetate

refractometer

DensityDensity

The The densitydensity of a material is defined as its of a material is defined as its massmass per unit per unit volumevolume

Density can be used to examine the Density can be used to examine the unknown sample qualitativelyunknown sample qualitatively

The measurement can use PICNOMETERThe measurement can use PICNOMETER

H3CH2C OH H3C C

O

CH3 H3C C

O

CH2CH3

= 0.789 g/cm = 0.79 g/cm = 0.897 g/cm

OPTICAL ROTATIONOPTICAL ROTATION

Optical rotation can be used to Optical rotation can be used to identify chiralityidentify chirality

OHOH

C OHC

HN

HH

HH

CH3

Cl