Medicine

A SECTION of І

Methodical instruction for students № 1.

 

Introduction into practical work. Rules of works and accident prevention. A.M. Butlerov theory of chemical structure. Classification, nomenclature and structural isomery of organic compounds. Acquaintance with a laboratory equipment and chemical glassware. Electronic structure of chemical connections, the conjugate systems, electronic effects. Methods of extraction and cleaning of organic matters (crystallization, filtration, extraction). Electronic structure of chemical bonds, the conjugate systems, electronic effects.

Methods of selection and cleaning of organic compounds: simple, fractious distillations, distillation with aquatic steam, distillation at the reduced pressure, extraction, filtration, recrystallization, sublimation.

 

The aim:

to master: a) basic points of Butlerov theory of chemical structure of organic compounds; b) principles of classification, nomenclature and structural isomery of organic compounds; с) rules of works and safety precautions in a chemical laboratory; d) to study the basic types of laboratory chemical glassware which is used for laboratory works; to formulate knowledge about the basic types of chemical bonds, electronic effects in the molecules of organic compounds; to master the basic methods of selection and cleaning of chemical compounds.

 

Practical skills:

a) To be able to determine belonging of organic compounds to the classes and to design its formulas;

b) To be able to use a laboratory equipment and chemical glassware

c) To be able to design the structures of molecules of organic compounds and to explain the formation of bonds;

d) To be able to construct the equipment and execute operations which are used for extraction and cleaning of compounds.

.

Illustrative material: test-tubes, stands for test-tubes, flasks, cylinders, pipettes, funnels, refrigerators, Bunsen, Vurts and Keldal flasks, glasses.

 

Professional motivation.

For the successful mastering of material of course of organic chemistry it is necessary to master the basic points of Butlerov theory of chemical structure of organic compounds; 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. The electrolytic, proton, electronic theory of acids and bases; classification of organic reactions and reagents; types of organic reactions and their mechanisms.

The course of organic chemistry predicts execution of both laboratory practical work and syntheses of organic compounds, and that is why mastering of basic rules of safety precautions during work in a chemical laboratory is  necessary for the safe and successful mastering of educational material from this course.

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 a extraction, cleaning and establishment of structure of medicinal preparations, are chemical and physico-chemical. And that’s why it is necessary for future pharmacist to master the basic methods of research of structure of organic compounds.

 

 

Students independent study program.

1. Theory of chemical structure of organic compounds of А.М. Butlerova.

2. Types of classifications of organic compounds by nature of functional groups and the structure of  Carbon chain. Basic functional groups and classes of organic compounds.

3. Nomenclature systems: (trivial, rational, international (IUPAC)). Basic principles of construction of the names of organic compounds according to the nomenclature of IUPAC.

4. Concept of isomery of organic compounds, spatial structure of molecules. Types of structural isomery: isomery of Carbon chain, isomery of position and isomery of functional group, metamerism, tautomery).

5. Basic types of laboratory glass. Chemical glassware and devices which are used in organic synthesis.

6. Types of flasks and their functions. Devices  for different types of distillation and its constructing.

7. Porcelain tableware and its usage. Measured and other glassware.

8.Butlerov’s theory of chemical structure of organic compounds.

9.   Types of chemical bonds in organic molecules (covalent, coordinatic, semipolar, ionic). A concept about hydrogen bond.

10. Quanto-mechanic bases of theory of chemical bond. Types of hybridization of atomic orbitals of atoms of Carbon, Nitrogen, Oxygen. Covalent s-and p-bonds, their description.

11. Electronic structure of double and triple Carbon-Carbon bonds and their description (length, energy, polarity).

12. Inductive effect.

13. The conjugate systems with the opened (butadiene, isoprene) and closed (benzene, naphthalene, anthracene, fenantren) chain. Types of conjugation: s,p-, p,p-, p, p-, р,р-. Influence of delocalisation on the increasing of stability of conjugate system. A concept of the resonance theory as qualitative method of description of delocalisation of electrons. Mesomeric effect.

14. Types of breaking of bonds (homolitic, heterolitic); intermediate particles (carbkation, carbanion, free radicals), their electronic structure.

15. Types of reagents (elektrophyls, nukleophyls, free radicals).

16. Major operations which are used during a extraction and cleaning of liquids (heating, cooling, filtration, weighing, measurement of liquids, dehydration).

17. Chemical tableware which is used for a selection and cleaning of liquids.

18. Process of extraction. Extracting from liquids; requirements to the solvent, extragents.

19. Recrystalisation, motion of its execution. Filtration. Motion of execution of filtration in vacuum. Sublimation.

 

 

Basic concepts of theme

Composition – Structure – Properties

Atoms of Carbon

Metamerism

Tautomeriya

Structural formula

Senior functional group

sp3, sp2, sp-hybridization

Aliphatic bonds

Heterocyclic bonds

Radical

Molecular formula

Isomery, isomers

Substutient

Carbocyclic bonds

Aromatic bonds

Structural isomery

Rational nomenclature

Homological row

Main hydrocarboxylic chain

International nomenclature

Radically-functional nomenclature

Trivial nomenclature

Functional group

Heteroatom     

Composition – Structure – Properties

Hydrogen bond

Semypolar bond

Ionic bond

Covalent bond

Conjugate systems

Simple bond

Atomic orbital

Free orbital

p-bond

Hybridization of atomic orbitals

s-bond

Energy of bond

Length of bond

Polarity of bond

Carbkation

Carbanion

Free radicals

Inductive effect

Mesomeric effect

 

Home task. 3, 5, 6, 7.

 

Tasks:

1. Formulate the basic points of Butlerov theory of chemical structure of organic compounds.

2. Give determination a concept: radical, functional group, isomery, homology. Give examples of radicals, functional groups, isomers, homologs, poli- and heterofunctional bonds.

3. Name functional groups of following medicinal preparations. What class and row of organic compounds does every compound belong to?

 

4. Name radicals of hydrocarbons:

5. Name the following compounds:

6.   Point all structural isomers of acyclic bonds of compound of С4Н10О and name them.

7.   Point all structural isomers of cyclic bonds of compound of С6Н12 and name them.

8.   Point all structural isomers of acyclic bonds of compound of С4Н8О and name them.

9.   Point the structural isomers of bonds of compound of С7Н9N, that contain a benzoic kernel, and name them.

10. Point all functional groups of the molecule of vanillin and name all bonbs.

vanilline

11. Write the structural formulas of connections:

1) cyclohexane;

2) ethanol;

3) propantriol;

4) butanon;

5) p-aminobenzoic acid.

12. Find structural isomers among the following formulas and name them:

12 Formulate the basic points of Butlerov theory of chemical structure of organic

compounds.

13. Name the types of chemical bonds in the following structural formulas

of compounds:

        nitroethane                        tetramethylammonium hydroxide                      ethanol

 

14. Hydrogen bond, his nature and designature. Hydrogen bond influence on the temperature of boiling, compounds solubility in water, viscidity, density. What following compounds can form hydrogen bonds: a) with its molecules and with the molecules of water; b) only with the

molecules of water.

1) СН3СН2СН2СН2ОН;

2) НО—СН2—СН2—ОН;

3) СН3—С(О)—СН3;

4) СН3-С(О)—H;

5) HC(О)—ОН;

6) СН3СН2Сl.

15. Explain, why acetate aldehyde of СН3—С(О)—H (t boiling = 20°С) and diethyl ether С2Н5—О—С2Н5 (t boiling = 36°С) boil at a lower temperature, than acetate acid СН3—С(О)—ОН (t boiling = 118°С). What these compounds are absolutely water-solubles?

16. Donor-acceptor bond. Its varieties: coordinatic and semypolar bonds.

17. Donor-acceptor bond. Semypolar bond influence on physical properties of molecule. Explain, why two following pairs of isomers differ by temperatures of boiling:

1) СH3—NO2 (t boiling = 101°С) and СH3—O—NO (t boiling = 12°С);

2) С2H5—NO2 (t boiling = 114°С) and С2H5—O—NO (t boiling = 17°С);

What is the structure of nitrogroup – NO2?

18. What types of hybridization of atomic orbitals are possible for the atoms of Carbon, Nitrogen, Oxigen and Sulfur in organic compounds?

    

       

Explain a form and spatial orientation of atomic orbitals. Why Carbon in organic compounds is fourvalency.

19. Quanto-mechanic presentations of molecular orbitals.

20. Give the determination s- and p- bonds. Describe the bonds on the example of molecules: СН3—СН3; CH3—C(O)—OH; H–CºN; CH2=CH—CH2—NH2. Name the type of hybridization of atoms of Carbon, Nitrogen, Oxygen.

21. Represent the atomic-orbital models of ethane, ethylene and acetylene. What are spatial structure of these molecules? Give description of Carbon-Carbon bonds in these molecules (length, energy, valency, polarity).

22. Inductive effect. Nature of its origin and distribution in molecule. Point 4-6 examples of atoms and groups which show: a) positive inductive effect; b) negative inductive effect

23. Designate the inductive effect of substutients in the molecules of the followings medicinal preparations:

        

diethyl ether                  aminalon                      chloralhydrate

             chloracon                                            glutamic acid

ephedrine hydrochloride                                  cycloserine

24. A concept of conjugation and electronic displacements in the conjugate systems. Types of conjugation: p,p-, p,р-, s, p- conjugation. Give 4-6 examples of atoms and groups which show: a) positive effect of conjugation, mesomeric effect; b) negative effect of conjugation or mesomeric effect.

Write, what types of conjugation are present in the following bonds? Name these conjugations and designate them:

1) H2N—CH=O;

2) C2H5—O—CH=CH2;

3) CH2=CH—NH2;

4) CH2=CH—CºN;

5) •CH2—CH3;

6) +CH2—CH=CH2;

7) CH2=CH—CH=O;

8) CH3—CH=O;

9) CH3—CH=CH2.

25. Show the division of electronic density, kind and sign of electronic effects in the molecules of the followings medicinal preparations and biologically active compounds:

    

             aspirine                                    salol                                        streptocid

 

anestesin                                                                                 adrenalin

  

pyridocsal                                     narcolan

26. What is named the resonance structures? On the example of phenol show delocalisation of electronic density with the help of resonance structures.

27. Give determination of the concept of “energy of resonance”. What does determine this term?

28. Name the types of hybridization of atoms in the molecule of pentene

29. Represent the scheme of electronic structure s– and p–bonds in the molecule of propene.

30. Define the type of conjugation in the molecule of the simplest unsaturated aldehyde – propenal (akrolein) – and represent blocking of p–orbitals in the conjugate system.

 

Tests.

1. What is the name of =NH group:

1.   nitrogroup;

2.   aminogroup;

3.   iminogroup;

4.   hydroxogroup;

5.   nitrozogroup.

2. What class this compound belongs to:

1.   alcohols;

2.   aldehydes;

3.   ketones;

4.   hydrocarboxylic acids

5.   simple ethers

3. The molecules of what following compounds contain donor-acceptor bond:

             

                            

4. Name the compounds with opened chain of conjugation in molecules:

                      

             

5. Define the molecules contain sp2-hybridizated atoms of Carbon:

                                

                              

 

Practical part.

 

Laboratory equipment and chemical glassware:

For laboratory experiments and syntheses in a chemical laboratory it is used the different types of chemical glassware. Physical and chemical properties of glass determine its type and sort. Such sorts of glass  have good firmness to the alkalis, acids and changes of temperature, is washed easily. All the kinds of glass well dissolve in HF acid.

Basic laboratory chemical glassware are: glasses, flasks, test-tubes, cups, funnels, refrigerators. Glasses of different volumes (fig. 1, a) are used for preparation of water solutions, dissolution of chemical compounds, for filtration, for reactions at a room temperature and at heating (not higher 100°С). It is impossible to use glasses for work with low boiling or inflammable solvents. Boxes, or glasses for weighing (fig. 1, b), are used for weighing and storage of hygroscopic compounds. Cups (fig. 1, c, d) are used for crystallization, sublimation, drying and other operations.

                            

                               а                                               b                     c                      d

Fig. 1. Glasses, boxes, cups.

 

 

There are 4 types of flasks (fig. 2): flat-bottom, conical, round-bottom, measured.

 

                      

а                  b                    c                  d            e               f                 g                  h

       

i                      j                  k                l

Fig. 2. Flasks: a) flat-bottom; b) round-bottom; c) round-bottom 100 ml; d) measured; e) Keldal flask; f) Bunzen flask; g) conical; h) conical 100 ml; i) 3-neck round-bottom; j) 2-neck round-bottom; k) pearlike; l) round-bottom for distillation.

 

 

For extraction round-bottom flasks are used  with reverse refrigerator (fig. 3,5). For more difficult operations (synthesis) with heating the special flasks are used. These are 2-, 3- or 4-neck round-bottom flasks (fig. 4).

             

   

 

Fig. 4.  Devices for  synthesis.

 

                   

 

Fig. 5. Types of refrigerators.

 

 

For connection of refrigerators and flasks it is used different connecting elements (fig. 6).

 

  

Fig. 6. Connecting elements.

 

For experiments it is used the test-tubes of different volume fig. 7).

Funnels in a chemical laboratory are used for pouring, filtration and division of liquids (fig. 8).

 

                     

                                        í              а            ý          b             c         í          d       ý      

Fig. 8. Funnels: a) laboratory funnel; b) filter funnel; c) Bunsen flask with Buchner funnel; d) separatory funnel.

 

Exycators  (fig. 9) are used for drying of compounds in vacuum and for storage of hygroscopic compounds.

      í              а                ý                 b

Fig. 9. Exycators:a) vacuum; b) ordinary

 

For measuring of different volumes of liquids it is used the measured cylinders (fig. 10, a), pipettes (fig. 10,b), and for  titration  it is used  burette (fig. 10, c).

In laboratory the tableware from porcelain is used: glasses, cups, mortars crucibles, spatulas, and other (fig. 11).

 

                   

Fig.. 11. Porcelain tableware

 

For construction and fixing of different glassware in a chemical laboratory it is used stands with the sets of rings, holders (fig. 12).

       

       а                                    б                                                 в

Fig. 12. A laboratory stand with the set of rings and holders.

 

 

For test-tubes it is used stands from stainless steel, aluminum or plastic (fig. 13).

Fig. 13. Stand for test-tubes.

Experiment 1. Crystallization.

            Reagents: benzoic or oxalic acids.

Equipment and materials: glasses 75-100 ml, test-tubes, funnels, filter paper, hot plate.

Crystallization is the important method of cleaning of hard compounds. For this purpose it is necessary to dissolve dirty compound in one of solvents, to heat, to filter hot solution from insoluble admixtures or dirt, and then to cool the filtrate.

Crystallization depends on the choice of solvent. A compound must dissolve badly in cold solvents and good at heating. A solvent must not react with dissolved compounds.

Table 1

Dissolving of compounds

Class of compound

Solvents

Hydrophobic properties

Hydrocarbons, halogen derivatives of hydrocarbons, ethers

Hydrocarbons, ethers, halogenderivatives of hydrocarbons

Amines, esters, nitrocompounds

Esters

Nitriles, ketones, aldehydes

Alcohols, dioxane, acetate acid

Phenols, amines, alcohols, carbon acids, sulphoacids

Alcohols, water

 

Hydrophylic properties

Salts

Water

 

In occasion for rekrystallisation it is used mixture of solvents: for example, water + dioxane, water + alcohol, chloroform + petroleum ether and etc.

Technique of experiment. Bring in a test-tube 0,5 g of dirty benzoic acid and add 5—6 ml of water. Heat the mixture to beginning of boiling; benzoic acid must absolutely dissolve. Filter the hot concentrated solution through a little fluted filter (fig. 15) and divide into two parts. Cool one part quickly by immersion of test-tube in cold water, benzoic acid will turn as small crystals. Slowly cool down on air other part of hot solution (20-25 minutes); benzoic acid will turn as beautiful large crystals.

Dissolve in a test tube 2 g oxalic acid, add 5 ml of water, heat, then filter, divide solution into two parts and cool both parts with different speed, as in previous experiment. Crystals of oxalic acid are like as needles; the size of crystals depends on speed of cooling.

Filter the crystals of benzoic (or oxalic) acid on the Buchner funnel with sucking (fig. 15). After sucking, wash sediment a few drops of cold water, suck again, carry sediment on the sheet of filter paper and dry.

 

Experiment 2. Filtration.

   Filtration is used for dividing a solvent from dissolved admixtures. For this purpose use Buchner funnel and Bunsen filter flask (fig. 1) with fluted filter (fig. 1).

Before filtration the bottom of funnel cover by filter paper.

 

Experiment 3. Extraction.

            Reagents: aniline, carbon tetrachloride, water.

            Equipment and materials: laboratory stand, separatory funnel, conical flask.

Extraction is a transition of compound from one phase to other liquid phase. This method based on different solubility of compounds in different solvents (solvent and extragent). During extracting of liquid compounds it is needed the extragent and the solvent not mix up. Extraction is executed directly in a separatory funnel. Diethyl ether, benzol, chloroform, amyl alcohol and other organic solvents are ekstragents.

The process of extraction accord to the Nernst law: , where C — are concentrations of matters in phases A and B; K — is a coefficient of division.

Technique of experiment. Bring 15 ml of aniline  (C6H5NH2) in separatory funnel (100-250ml) and add 30 ml of water. Add 10 ml CCl. Then shake it several times (fig.2). In the process of extraction aniline passes to the phase of carbon tetrachloride. Leave the mixture for some  time to share 2 phases. Then divide the lower phase in dry glass. Extract the upper phase 2 times more.

Fig.2. Extraction in separatory funnels.

 

Experiment 4. Sublimation.

Reagents: naphthalene.

Equipment and materials: porcelain cup, funnel, hot plate, filter paper, cotton.

Sublimation  is a transition of compound from the hard state directly to gaseous (without melting). After cooling a hard phase appears again. Not all compounds are able to be sublimated. As an example, naphthalene, benzoic acid, salicylic acid, quinones  are able to be sublimated.

Technique of executing of experiment. In a porcelain cup place a few crystals of naphthalene. Cover this cup by filter paper with openings. Above it put a funnel, closed cotton. Wet filter paper cools the walls of funnel. Heat a cup carefully on hot plate. After some time the needle-shaped crystals of naphthalene appear on the walls of funnel (fig. 3).

 

A student must know:

substantive provisions of theory of chemical structure of organic compounds;

types of chemical bonds;

types of hybridization of atomic orbital atoms of Carbon, Nitrogen, Oxygen;

basic descriptions of chemical bonds;

types of breaks of chemical bonds, types of reagents;

types of electronic effects, basic types of conjugations;

major operations which are used during a selection and cleaning of liquids (heating, cooling, filtration, weighing, measurement of liquids, dehydration, extraction, recrystalization, sublimation).

 

A student must be able:

to determine the types of chemical bonds in a molecule;

to predict the types of breaks of chemical bonds, according to basic descriptions of chemical bond;

to predict reactionary ability of bonds on the basis of electronic effects in a molecule;

to construct devices  and execute major operations which are used during a selection and cleaning of liquids (heating, cooling, filtration, weighing, dehydration, extraction, recrystalization, sublimation).

          basic points  of theory of chemical structure of organic compounds;

          types of classifications of organic compounds and their basic classes;

          principles of construction of the names of organic compounds according to the nomenclature of IUPAC;

          types of structural isomery of organic compounds;

          basic types of laboratory glass, chemical tableware and devices which are used in an organic synthesis;

          to give the names of organic compounds with the help of rational and international (IUPAC) nomenclature systems.

 

 

Prepared by assist. Burmas N.I.

Adopted at the Chair Sitting Minutes № 5

“19” June, 2008, Revised