Medicine

Methodical instruction

Methodical Instruction for Students of the 2 Course pharmaceutical Faculty

 

LESSON 2 (PRACTICAL – 6 HOURS)

 

Themes: 1. Methods of the organic compounds extraction and purification – distillation: simple, fractional, with aquatic steam, at the lower pressure). Methods of the determination of the organic molecules structure. Elemental analysis (determination of the Carbon, Hydrogen, Nitrogen, Sulfur, halogens). Solving problems on output formulas.

2. Acidic and basic properties of the organic compounds. Classification of the organic reactions and reagents.

 

Aim: to learn: а) the basic principles of classification of the organic reagents and reactions. b) the acidic and basic properties of the organic compounds. c) to master the basic stages of the purification (different types of distillations) and identification of the unknown organic compound and execute the qualitative element analysis of the organic compounds.

 

Professional orientation of students:

For the successful mastering of material from the course of organic chemistry it is necessary to master the basic points of Butlerov’s theory of chemical structure. basic principles of classification, nomenclature and types of isomery of organic compounds. basic types of chemical bonds, electronic effects in the molecules of organic compounds. acid and basic properties of organic acids. types of organic acids and bases. Electrolytic, proton, electronic theories of acids and bases. classification of organic reactions and reagents. types of organic reactions and their mechanisms.

90 % medicinal preparations are the compounds of organic origin, and most methods which are used in pharmaceutical practice for extraction, purification and establishment of the structure of the medicinal preparations are chemical and physico-chemical. And that’s why it is necessary for future pharmacist to master the basic methods of the researching of the structure of organic compounds.

 

Methodology of practical class (900-1200)

Illustrative material: Porcelain cups, test-tubes, filter paper, scalpel, pincers, Safety Goggles, cotton, mortar, hot plate, ab Burner, flasks, cylinders, pipettes, funnels, thermometer, condenser, allonge, adators.

Types of distillation and their usage

The process of distillation is of the great importance among the numerous methods of purification and secretion of the organic compounds. The purpose of distillation is to divide the liquid components of mixture which have different temperatures of boiling.

Distillation is the process, when compounds which are in the mixture are transformed from mixture to steamy state by heating. steam is condensed in a liquid distillate in the condenser.

There are four types of distillation processes: Simple distillation, Vacuum distillation, Vigreux (Fractiona) distillation and Steam distillations.

Experiment 1. Simple distillation at atmospheric pressure and determination of boiling temperature.

Reagents: ethanol, benzene, chloroform, methanol, carbon tetrachloride.

Equipment and materials: Bunsen spirit lamp, laboratory stands, asbestos net, Vurts flask, thermometr, Libikh condenser, allonge, receiving flask.

Any liquid evaporates until pressure of its steam will not reach some point that is characteristic for this liquid at certain temperature. Pressure of the saturated steam does not depend on the amount of liquid which evaporates. With the increase of temperature the pressure grows and at certain temperature it reaches atmospheric pressure. This temperature is named the temperature of boiling of this compound. It is major physical and chemical description of liquid compound.

Simple distillation of compound at atmospheric pressure is used in following cases:

1. For verification of cleanness of compound by determination of boiling temperature and boiling temperature interval. Clean compounds are distillated in the interval of 1-2°С. For identification of compound it is necessary to compare received point of boiling temperature and the point of boiling temperature (at the same pressure) of the same compound from original literature.

2. For dividing of liquid from hard or compounds dissolved in it.

3. For dividing of mixtures of liquids, when their temperatures of boiling differ more than 80°С (for example, for dividing ether and phenol solution. boiling temperature of diethyl ether is 34,5°С, phenol — 183°С).

Technique of experiment. For simple distillation construct the device (fig. 1).

Fig. 1. The device for simple distillation of liquid compounds:1) Bunsen spirit lamp. 2) a ring with pincer and asbest net. 3) Vurts flask. 4) grip with pincer. 5) a thermometr. 6) stands. 7) Libikh condenser. 8) allonge. 9) a receiving flask.

 

In a flask pour a liquid which must be distillated and heat to its boiling. The temperature of boiling of every compound is determined in the moment of dropping the first drop of liquid from the condenser. Constancy of boiling point of liquid means about its cleanness.

Experiment 2. Fractional distillation and determination of boiling temperature of liquids.

Reagents: mixture of aniline and carbon tetrachloride.

Equipment and materials: Bunsen spirit lamp, laboratory stands, asbestos net, flask, deflegmator, thermometr, Libikh condenser, allonge, receiving flask.

Using this method divide liquids in mixture which differs by the boiling temperatures on 50-80 °С.

Technique of experiment. For execution of fractional distillation construct a device (fig. 2).

Fig. 2. A device for fractional distillation: 1) a flask. 2) deflegmator. 3) a thermometer. 4) a Libikh condenser. 5) allonge. 6) a receiving flask.

Pour in a flask the mixture of aniline and carbon tetrachloride, which is needed to be divided, and heat to boiling. Every liquid has its boiling temperature. The temperature of boiling of every compound is determined in the moment of dropping the first drop of liquid from the condenser.

Experiment 3. Distillation with aquatic steam.

Reagents: mixture of aniline and water.

Equipment and materials: laboratory stands, Keldal flask, Libikh condenser, allonge, receiving flask.

This type of distillation is used for the division of liquids which limitedly dissolve in water, for example, aniline, essential oils.

Technique of experiment. For work construct a device (fig.3).

Fig.3. A device for distillation with aquatic steam:1) steam-maker. 2) Keldal flask. 3) Libikh condenser. 4) allonge. 5) a receiving flask.

In Keldal flask pour 35 ml of aniline and 35 ml of water, heat steam-maker to formation of steam. Distillation lasts 1-1,5 hours. If the distillate is lees the distillation is over. For selection aniline add 25 g of salt to the distillate per each 100 ml of liquid and after complete dissolution of salt extract aniline by chloroform three times. Determine the boiling temperature of aniline.

Experiment 4. Distillation in vacuum.

Reagents: cyclohexanone, dimethylformamide, tetraline, o-toluidine.

Equipment and materials: laboratory stands, Claisen flask with a thermometer and capillary, condenser, allonge, receivers, glass, manometer, vacuum pump.

At the distillation of organic compounds with high boiling temperatures (more than 150°С). It is necessary to distillated in a vacuum. Reducing of pressure in a device is usually created by water or oily vacuum pump. For most organic compounds the reducing of pressure on 20 mm mercury reduces a boiling temperature on 100-120°С.

Attention! During work with a vacuum it is necessary to use round bottom flask only, it is necessary to wear protective glasses or mask.

Technique of experiment. For distillation in vacuum construct the device (fig. 4).

Fig.4. The device for vacuum distillation:1) Claisen flask. 2) capillary. 3) thermometer. 4) condenser. 5) an allonge-spider. 6) receivers. 7) glass. 8) a manometer.

Connect all parts of device. Check the impermeability of device before the beginning of work. Then pour the liquid in the half of flask, close it by a cork with a thermometer, turn in a pump and block connection of device with an atmosphere. Close a clamp on a capillary that through it air passes at the speed of 5-6 blisters per second. Open a manometer. After pressure is permanent the distillation begins. A compound must be distillated with the speed 1-2 drops per second.

After distillation stop the heating, cool the flask and align the pressure in a device.

Experiment 5. Test on the determination of Carbon by charring.

Reagents: sucrose or glucose, concentrated H2SO4.

Equipment and materials: scalpel, mortar, 50 ml glasses, hot-plate.

Charring is the simplest test on the determination Carbon in organic compounds. Some organic compounds char at high temperature and at the action of concentrated H2SO4.

Technique of experiment. a) On the tag of scalpel bring a few crystals of sucrose or glucose in flame, charring of carbohydrates begins, the characteristic smell of the charred sugar appears.

b) In a mortar powder 2 g of sugar, add a few drops of water and put this mixture in a test-tube. Then at continuous stirring of mixture add 1 ml of concentrated H2SO4.

Experiment 6. Determination of Carbon and Hydrogen by the reaction of oxidation with copper (ІІ) oxide.

Reagents: sucrose, copper (ІІ) oxide (powder), Ca(OH)2 (solution is saturated), waterless copper (ІІ) sulfate.

Equipment and materials: test-tubes with corks, stand, cotton.

Technique of experiment. In a dry test-tube bring the mixture of sucrose and copper (ІІ) oxide (1:10) (0,1-0,3 g of sucrose and 1-3 g of powder of copper (ІІ) oxide). Then the mixture cover by copper (ІІ) oxide (1 g). In upper part of test-tube it is necessary to put a piece of cotton covered by waterless copper (ІІ) sulfate (fig. 5).

Fig.5. The device for determination of Carbon and Hydrogen in compounds: 1) dry test-tube with mixture of CuSO4 and sucrose. 2) test-tube withCa(OH)2

Close the test-tube by cork with a gas-pipeline. Free end of gas-pipeline put into the test-tube with Ca(OH)2.

1) What reaction teaks place in the second tube with Ca(OH)­2?

2) Why does the color of waterless сopper (ІІ) sulfate change?

Experiment 7. Determination of Nitrogen by the Lassen reaction.

Reagents: urea, metallic sodium, 5% solution of iron (ІІ) sulfate, 1% solution of iron (ІІІ) chloride, 10% solution of HCl, ethanol.

Equipment and materials: test-tubes, filter paper, scalpel, pincers, porcelain cup.

Metallic sodium alloys with organic compound, and organic compound destroys. Nitrogen, Carbon and Sodium form sodium cyanide:

Organic compound that contain N+ Na →NaCN+ …

Technique of experiment. In a dry test-tube put 25-30 mg of the explored compound, for example urea, and add the small piece of metallic sodium very carefully. Heat it and cool. Then add ethanol to determine sodium didn’t react with urea. Add 2 ml of water, heat and filter.

To filtrate add 2-3 drops of 5% solution of FeSO4. Green sediment of Fe(OH)2 falls and partly oxidizes to Fe(OH)3 (brown colour). Then add 2-3 drops of mixture of 1% solution of FeCl3 with 10% solution of HCl.

In solution there is a row of chemical processes which can be expressed such equations:

FeSO4 + 2NaOH ® Fe(OH)2¯ + Na2SO4

FeCl3 + 3NaOH ® Fe(OH)3¯ + 3NaCl

Fe(OH)2¯ + 2HCl ® FeCl2 + 2H2O

Fe(OH)3¯ + 3HCl ® FeCl3 + 3H2O

2NaCN + FeCl2 ® Fe(CN)2 + 2NaCl

Fe(CN)­2 + 4NaCN ® Na4[Fe(CN)6]

Na­4­[Fe(CN)6] « 4Na+ + [Fe(CN)6]4–

4Fe3+ + 3[Fe(CN)6]4– ® Fe4[Fe(CN)6]3¯

Experiment 8. Determination the Sulfur by allowing of organic compound with metallic sodium.

Reagents: thiourea, metallic sodium, 2 % solution of (CH3COO)2Pb (ІІ), 2 % solution of Na2[Fe(CN)5NO], 10 % solution of HCl, ethanol, acetate acid.

Equipment and materials: test-tubes, filter paper, scalpel, pincers, porcelain cup.

Metallic sodium alloys with organic compound, and organic compound destroys. Sulfur forms Na2S:

Organic compound that contain S + Na → Na2S + …

Technique of experiment. In a dry test-tube put 500 mg of thiourea and small piece of metallic sodium very carefully. Heat it and cool. Then add ethanol to determine sodium didn’t react with urea. Add 2 ml of water, heat and filter. Pour the filtrate in 3 test-tubes.

1) In the first test-tube add acetate acid and 0,5 ml of 2% solution of lead acetate. A liquid becomes brown or black or black sediment appears.

Write equation of reaction.

b) In the second test-tube add 0,5 ml of 2 % solution of Na2[Fe(CN)5NO]. The intensive red-violet colour appears which gradually changes to brown colour.

Write equation of reaction.

c) In the third test-tube add 10 % HCl, the smell of H2S appears here.

Write equation of reaction.

Experiment 9. Determination of halogens.

Reagents: chloroform, 10% solution of HCl.

Equipment and materials: test-tubes, filter paper, scalpel, pincers, porcelain cup.

а) Beilshtein test. It is possible to determinate halogens in organic compounds by heating copper wire in flame. Carbon turn into carbon (IV) oxide, Hydrogen – in water, and halogens (except fluor) form with wire compounds that paint flame in bright green colour. A reaction some advantages and disadvantages. A positive result means the presence of halogens. A negative result means their absence.

Technique of experiment. A wire moistening in solution of HCl, bring in flame. The flame will be painted, and a black copper (ІІ) oxide will appear on the surface of wire. Cool it. Then dip it in compound that contain halogen and bring it again in flame. At first Carbon burns (the flame becomes yellow), and then the flame becomes green (it means that copper halogenides appear. If chloroform is used, the equation of reaction will look like followed one:

2CHCl3 + 5CuO ® CuCl2 + 4CuCl + 2CO2 + H2O

Basic concepts of the theme

Composition – Structure – Properties

Elemental analysis

Distilation

Boiling temperature

Accession

Substitution

Elimination

Regrouping

Oxidation-reduction

Nucleophilic reagent

Electrophilic reagent

 

Individual students program.

1. Elemental analysis. Determination of the Carbon, Hydrogen, Nitrogen, Sulfur and halogens.

2. Main types of distillation:

a) distillation at atmospheric pressure.

b) fractional distillation.

c) distillation with aquatic steam.

d) distillation in vacuum.

3. Laboratory equipment that are used for the distillation.

4. Acidic and basic properties of the organic compounds.

5. Types of organic acids and bases.

6. Classification of the organic reactions:

a) reactions of the accession.

b) reactions of the substitution.

c) reactions of elimination.

d) regrouping reactions.

e) oxidation-reduction reactions.

7. Classification of the organic reagents:

- nucleophilic reagents.

- electrophilic reagents.

 

Seminar discussion of theoretical issues (1230 – 1400 hour).

Test evaluation and situational tasks.

Home task. 4, 7, 8.

1.     Hydrocarbon composition is: C - 82.76 %, H - 17.24 %. Pairs of hydrocarbon have volume 1,12 l (n. c.) with a mass of 2.9 g. At the radical monobrominationthis alkane forms two isomers of alkyl bromide - primary and tertiary. What is the name of this hydrocarbon?

2.     Mass fraction of carbon in hydrocarbon is 83.33%. Density of the substance’ vapor by the hydrogen is 36. Determine the formula of hydrocarbon. Write structural formulas of all its isomers and name them by IUPAC nomenclature.

3.     When burning compound X with mass 3.2 grams formed 7.2 grams of water and 4.48 l of CO2 (n. c.). Relative density of the pair of this compound by hydrogen is 8. Identify formula of this compound.

4.     Mixed 40 ml of hydrocarbon with 200 ml of oxygen taken in excess. Burned the mixture. After reduction to normal conditions volume is 140 ml, 80 ml of which is absorbed by alkali at the transmittance of gases through it. Determine the formula of hydrocarbon.

5.     When burning a certain mass of substance, which includes Carbon, hydrogen and chlorine was extracted 0.44 g of Carbon (IV) oxide and 0.18 g of water. From chlorine, which was located in this mass of matter, after its transformation into the chloride-ion was extracted 2.86 g silver chloride. Define the formula of the substance.

6.     Hydrocarbon with mass of 4.3 g completely burned. Mass of the formed Carbon (IV) oxide - 13.2 g. The relative density of the vapors by air - 2,966. What is the molecular formula of compound? Write it hemistructual formula and formulas of the two isomers and the two closest homologs. Name them.

7.     At the interaction of 0.5 liters of the 5 % solution (density 0.75 g/ml) of monoatomic alcohol with unknown structure in diethyl ether with metallic sodium evaporates 3.36 liters of gas. Suggest a possible structural formulas of alcohol.

8.     Mass fraction of elements in organic substance: Carbon - 69.77 %, hydrogen - and oxygen 11.63 %. Density of pairs of the substance by ethyne - 3.31. Find the molecular formula of a substance. Write at least three of its isomers and name them.

9. As a result of homolytic cleavage of the chemical bond are formed?

A. cations and anions

B. only cations

C. free radicals

D. free radicals and ions

E. only anions

10. In which of the following sequences the acidity of the acidic centers for the shown below structure is decrease?

11. Define a character of the bond cleavage as a result of which the particles having one not coupled electron are formed:

A. heterolytic

B. homolytic

C. ionic

D. pericyclic

E. molecular

 

Correct answers of test evaluations and situational tasks:

9. C. 10. C. 11. B.

 

Individual student work (1415-1500 hour) are checked by solving situational tasks for each topic, answers in test evaluations and constructive questions (the instructor has tests & situational tasks).

 

Student should know:

basic principles of the classification of the organic reagents and reactions.

– types of distilation.

acidic and basic properties of the organic compounds.

– basic stages of the selection and identification of the unknown organic compound.

 

Student should be able to:

–to predict the type of organic reactions.

–to know the methods of determination of qualitative composition of organic compounds.

–to execute the qualitative element analysis of organic compounds.

–to designate the formula of organic molecules on the basis of experimental information.

–to determine the basic and acidic properties of the organic compounds.

–to construct the devices and execute major operations which are used for secreting of organic compounds – to execute the distillation.

 

References:

Main:

1.     Clayden Jonathan. Organic Chemistry. Jonathan Clayden, Nick Geeves, Stuart Warren // Paperback, 2nd Edition. – 2012. – 1234 p.

2.     Bruice Paula Y. Organic Chemistry / Paula Y. Bruice // Hardcover, 6th Edition. – 2010. – 1440 p.

3.     Brückner Reinhard. Organic Mechanisms - Reactions, Stereochemistry and Synthesis / Reinhard Brückner // Hardcover, First Edition. – 2010. – 856 p.

4.     Moloney Mark G. Structure and Reactivity in Organic Chemistry / Mark G. Moloney // Softcover, First Edition. – 2008. – 306 p.

5.     Carrea Giacomo. Organic Synthesis with Enzymes in Non-Aqueous Media / Giacomo Carrea, Sergio Riva // Hardcover, First Edition. – 2008. – 328 p.

6.     Smith Michael B. March's Advanced Organic Chemistry. Reactions, mechanisms, and structure / Michael B. Smith, Jerry March // Hardcover, 6th Edition. – 2007. – 2384 p.

7.     Carey Francis A. Advanced Organic Chemistry / Francis A. Carey, Richard A. Sundberg // Paperback, 5th Edition. – 2007. – 1199 p.

8.     http://intranet.tdmu.edu.ua/data/kafedra/internal/gen_him/classes_stud/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lesson_02.Elemental analysis. Acidic and basic properties of the organic compounds.

9.     http://intranet.tdmu.edu.ua/data/kafedra/internal/gen_him/presentations/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lecture_01. Chemical connection and mutual influence of the atoms in the organic compounds’ molecules.

Additional:

1.     Francotte Eric. Chirality in Drug Research / Eric Francotte, Wolfgang Lindner // 
Hardcover, First Edition. – 2006. – 351 p.

2.     Quin Louis D. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals / Louis D. Quin, John Tyrell // Hardcover, 1st Edition. – 2010. – 327 p.

3.     Zweifel George S. Modern Organic Synthesis - An Introduction / George S. Zweifel, Michael H. Nantz // Softcover, 1st Edition. – 2007. – 504 p.

4.     K. C. Nicolaou. Molecules that changed the World / Nicolaou K. C., Tamsyn Montagnon // Hardcover, First Edition. – 2008. – 385 p.

5.     Mundy Bradford P. Name Reactions and Reagents in Organic Synthesis / Bradford P. Mundy, Michael G. Ellerd, Frank G. Favaloro // Hardcover, 2nd Edition. – 2005. – 886 p.

6.     Li Jie Jack. Name Reactions. A Collection of Detailed Reaction Mechanisms / Jie Jack Li // Hardcover, 4th Edition. – 2009. – 621 p.

7.     Gallego M. Gomez. Organic Reaction Mechanisms / M. Gomez Gallego, M. A. Sierra // Hardcover, First Edition. – 2004. – 290 p.

8.     Sankararaman Sethuraman. Pericyclic Reactions - A Textbook / Sethuraman Sankararaman // Softcover, First Edition. – 2005. – 418 p.

9.     Tietze Lutz F. Reactions and Syntheses / Lutz F. Tietze, Theophil Eicher, Ulf Diederichsen // Paperback, First Edition. – 2007. – 598 p.

10. Olah George A. Superelectrophiles and Their Chemistry / George A. Olah, Douglas A. Klumpp // Hardcover, First Edition. – 2007. – 301 p.

11. Grossmann Robert B. The Art of Writing Reasonable Organic Reaction Mechanisms / Robert B. Grossmann // Hardcover, 2nd Edition. – 2003. – 355 p.

12. Cole Theodor C.H. Wörterbuch Labor - Laboratory Dictionary / Theodor C.H. Cole // Hardcover, 2nd Edition. – 2009. – 453 p.

 

The methodical instruction has been worked out by: Associate Prof. Dmukhulska Ye.B., assistant Medvid I.I., assistant Burmas N.I.

 

 

 

Methodical instruction was discussed and adopted at the Department sitting

25.06.2013. Minutes N 11

 

Methodical instruction was adopted and reviewed at the Department sitting

27.08.2013. Minutes N 1