Methodical Instruction for Students of the 2 Course pharmaceutical Faculty
LESSON № 22 (PRACTICAL – 6 HOURS)
Themes: 1. Carbohydrates. Monosaccharides. Structure, classification, stereoisomery. Determination of the value of the angle of the specific rotation of the glucose’s.
2. Monosaccharides. Chemical properties. Small practicum.
Aim: To learn: the structure, classification, nomenclature, isomery, methods of obtaining and chemical properties of monosaccharides.
Professional orientation of students.
Carbohydrates are the most abundant class of bioorganic molecules on planet Earth. Although their abundance in the human body is relatively low, carbohydrates constitute about 75% by mass of dry plant materials.
Green (chlorophyll-containing) plants produce carbohydrates via photosynthesis. In this process, carbon dioxide from the air and water from the soil are the reactants, and sunlight absorbed by chlorophyll is the energy source.
Plants have two main uses for the carbohydrates they produce. In the form of cellulose, carbohydrates serve as structural elements, and in the form of starch, they provide energy reserves for the plants. Dietary intake of plant materials is the major carbohydrate source for humans and animals. The average human diet should ideally be about two-thirds carbohydrate by mass.
Carbohydrates have the following functions in humans:
1. Carbohydrate oxidation provides energy.
2. Carbohydrate storage, in the form of glycogen, provides а short- term energy reserve.
3. Carbohydrates supply carbon atoms for the synthesis of other biochemical substances (proteins, lipids, and nucleic acids).
4. Carbohydrates form part of the structural framework of DNA and RNA molecules.
5. Carbohydrate “markers” on cell surfaces play key roles in cell -cell recognition processes.
Methodology of Practical Class (900-1200).
Carbohydrate classifications: Most simple carbohydrates have empirical formulas that fit the general formula СnН2nОn. An early observation by scientists that this general formula can also be written as Сn(Н2О)n is the basis for the term carbohydrate – that is, “hydrate of carbon.” It is now known that this hydrate viewpoint is not correct, but the term carbohydrate still persists. Today the term is used to refer to an entire family of compounds, only some of which have the formula СnН2nОn.
Carbohydrates are polyhydroxy aldehydes, polyhydroxy ketones, or compounds that yield such substances upon hydrolysis. The carbohydrate glucose is а polyhydroxy aldehyde, and the carbohydrate fructose is а polyhydroxy ketone.
Monosaccharides are carbohydrates that contain a single polyhydroxy aldehyde or polyhydroxy ketone unit. Monosaccharides cannot be broken down into simpler units by hydrolysis reactions. Both glucose and fructose are monosaccharides. Naturally occurring monosaccharides have4rom three to seven carbon atoms; five- and six-carbon species are especially common. Pure monosaccharides are water-soluble, white, crystalline solids.
Experiment 1. General reaction on carbohydrates with α-naphthalene (Molysh reaction).
Reagents: glucose, fructose, sucrose, starch, cellulose, 10 %- alcoholic solution of a– naphthalene, conc. H2SO4.
Technique of the experiment. To the separate test-tubes pour for 0,1- 0,2 g of different carbohydrates: glucose, fructose, sucrose, starch, cellulose and others. To the every test-tube add for 2-3 ml of water and 3-4 drops of 10 % alcoholic solution of α-naphthalene. Content of the test-tubes is mixed and carefully, because liquid should not be mixed up, add 1,5-2 ml of the concentrated sulfate acid which goes down on the bottom of test-tube. There is a beautiful red-violet ring on the verge of two layers. It is explained by formation of furfural.
All carbohydrates give reaction with α––naphthalene. In the practice, fructose reacts as follows:
Experiment 2. Petroleum-resorcinol Tollen’s test (the general reaction on carbohydrates)
Reagents: glucose, 1% alcoholic solution of petroleum-resorcinol, conc. HCl, diethyl ether (or benzene).
Technique of the experiment. To the test-tube bring a few crystals of glucose, 5 ml of water and 1 ml of 1% alcoholic solution of petroleum-resorcinol and 1 ml of the concentrated HCl. Mixture is carefully boiled during 1 minute, then cooled and shaken of with 5 ml of diethyl ether or benzene. Ether layer is painted in different colours: glucose, mannose, galactose have the blue-green colouring; ramnose – violet; arabinose and xylose – dark-blue. Appearance of the colouring is cased by formation of the products of glucuronic acid condensation with petroleum-resorcinol with formation of dinaphthylamine (I) or xanthene (II) derivatives:
Uronic acids paint ether layer in violet color.
Experiment 3. Proofing of the presence of hydroxyl groups in monosaccharides.
Reagents: 5% solution of CuSO4; 10% solution of NaOH; 5% solution of glucose; liquid of Felling.
A) Interaction of carbohydrates with Cu(OH)2.
Technique of the experiment. Experiment is carried out in two test-tubes to each of theme bring 1 ml of 5% solution of CuSO4 and 1 ml of 10% solution of NaOH. After it to the got sediment of Cu(OH)2 in one test tube add 5% solution of glucose, and in the second test tube – 5% solution of fructose. Get clear blue solutions of copper glucosate and fructosate complex compounds. Polyhydric alcohols give a similar reaction with copper (II) hydroxide and, therefore, glucose, fructose (and other monosaccharides) are polyhydric alcohols.
B) Cooperating of carbohydrates with liquid of Felling.
Technique of the experiment. To three test tubes bring for 1 ml of 1% solutions of glucose, maltose and starch. In every test tube add 2 ml of Felling liquid. All solutions are painted in the blue colour which specifies the presence of polyatomic alcohols.
Experiment 4. Proofing of the presence of aldehyde group in monosaccharides.
Reagents: 5% solution of glucose, 5% solution of fructose, 5% solution of maltose, 5% solution of formaldehyde, fuchsine sulfite acid, 10%-solution of NaOH, 5% solution CuSO4, liquid of Felling, 1% solution of AgNO3, ammonium.
A) Cooperating of monosaccharides with ammonia solution of silver oxide (“silver mirror” reaction).
Technique of the experiment. In the test-tube bring 1 ml of 1% solution of AgNO3 and add by drops ammonium to the complete dissolution of AgOH. To the ammonia solution of silver oxide add 3 ml of 5% solution of glucose and heat on the water-bath. On the walls of test- tube free silver is besieged as a mirror raid or grey sediment. Experiment is repeated, but instead of glucose solution to the reactionary mixture add the same amount of 5% solution of fructose. So, fructose solution also has reductive properties. This is due to the fact that under the action of alkali fructose isomerizes to glucose and mannose that reduce by the ammonia solution of silver oxide:
This reaction is specific on aldoses and reductive disaccharides.
B) Reduction of monosaccharides by Cu(OH)2 at the presence of alkali (Trommer’s test).
Technique of the experiment. In alkali medium at the heating monosaccharides reduce Cu(OH)2 to Cu2O. To the two test tubes bring 1-2 ml 10% solution of NaOH and add: to the first – 2 ml of glucose, to the second– 2 ml of maltose. To the mixture at the permanent shaking add by drops CuSO4 to stable clouding. During the heating at first the blue coloring changes on green, and then discolors. At the same time yellow sediment of CuOH appears which changes into the red-orange sediment of Cu2O. Maltose gives the same reactions.
Write appropriate reaction, show redox process.
C) Interaction of monosaccharides with Felling liquid.
Technique of the experiment. To the test- tube bring 2 drops of water solution of CuSO4 (Felling I) and 2 drops of alkaline solution of segnetic salt – sodium-potassium salts of tartaric acid (Felling II). Observe after the appearance of blue sediment of Cu(OH)2, which with segnetic salt forms the water-soluble complex with blue color.
Then to the test-tube add 3 drops of 5% solution of glucose and resulting mixture is heated to the boiling. Observe the gradual discoloring of the solution and formation of the red-orange sediment of Cu2O.
D) Attitude of monosaccharides to fuchsine sulfite acid.
Technique of the experiment. To the two test tubes bring 1 ml of fuchsine sulfite acid solution. Then in one test tube add 1 ml of 5% solution of glucose, and in second -1 ml of 5% solution of formaldehyde. After some time in the test tube with formaldehyde the violet-pink color appears and reactionary mixture with glucose remains colorless.
Explain why glucose (and other aldoses) does not interact with fuchsine sulfite acid.
Experiment 5. Oxidation of monosaccharides by bromine water.
Reagents: saturated solution of bromine water, 2% solution of glucose, 2% solution of fructose, 1% solution of FeCl3 in complex with phenol.
Experiment is conducted under the drawing cupboard.
Technique of the experiment. To the two test tubes bring 3 ml of bromine water (saturated solution). Then in one of them add 0,5 ml of 2% solution of glucose, and in another – 0,5 ml of 2% solution of fructose. Test tubes with reactionary mixtures are closed by tampons of cotton wool, put in the boiling water-bathe and heat during 10-15 min. After the cooling add to the solutions few drops of 1% solution of FeCl3 in the complex with phenol.
What can you see?
Observe as the glucose solution colorless bromine water, whereas the coloration of the reaction mixture with fructose almost does not change. Thus, in contrast to fructose, glucose oxidizes by bromine water.
After the cooling to reactionary mixture which contains glucose add a few drops of 1% solution of FeCl3, painted by a phenol in the violet color. Green-yellow coloring appears.
Glucose oxidizes by bromine water to gluconic acid, which has five hydroxyl groups, one of which is in a-position to carboxyl group. Therefore, this acid gives character color reaction on a-hydroxyacids with iron (III) chloride.
It is shown that glucose oxidant (and other aldoses) is bromine, not bromic acid, which is in the equilibrium with it in bromine water. Glucose oxidizes by bromine initially in d-lactone, this means that the monosaccharides subjected to oxidation in cyclic (pyranosic) form. d-lactone then attaches the water and converts to gluconic acid.
d-lactone
Experiment 6. Formation ozazones of glucose and fructose.
Reagents: 5% solution of glucose, 5% solution of fructose, chloride salt of phenylhydrazine, sodium acetate.
Experiment is conducted under of drawing cupboard.
Technique of the experiment. In two test-tubes bring a few crystals of chloride salt of phenylhydrazine and sodium acetate. Then in one of them add 5 drops of 5% solution of glucose, and in the second – 5 drops of 5% solution of fructose. Then both test tubes heat on the boiling water-bath during 40 minutes. Thus yellow needle-shaped crystals of glucose ozazones and fructose ozazones fall out. Cooling mass of sediment increases during that time.
Experiment 7. Qualitative reactions on pentoses.
Reagents: 0.1% solution o ribose, conc. hydrochloric acid, ortsyne, aniline, 2 H solution of acetic acid, acetic acid ice solution.
Equipment and materials: test-tubes, filtration paper, photoelectrocolorimeter (PEC) cuvettes.
a) reaction on pentoses with ortsyne (Bial reaction). At the heating pentose with hydrochloric acid formed furfural, which with ortsyne forms a green color.
Technique of the experiment. In test tube put 2 ml of 0,1% solution of pentose (ribose) and 2 ml, prepared by mixing of 2 ml of concentrated hydrochloric acid, several crystals of ortsyne (5-methylresorcinol) and 1 drop of 3% solution of iron (III) chloride. Mixture is shaking and boiling for 5 minutes. Products of reaction are extracted with amyl alcohol. The organic layer paints in green color.
Reaction scheme:
Glucose, galactose and fructose in these conditions, paint the organic layer in brown color.
b) Formation of furfural and its condensation with aniline.
Technique of the experiment. In the test tube pour layer of chips height of 15-20 mm or few crystals of arabinose (or 0,1-0,2g of cherry glue), wet them by the separately prepared mixture of concentrated hydrochloric acid and water (1 : 1), mix and boil for 2-3 minutes. Wet a narrow strip of filter paper with a mixture of aniline and 4 drops of 2 H acetic acid and bring to the opening of the tube. After some time on this paper bright red stain will appear.
Reaction mixture is cooled in test tube and add to it 0,5-1 ml of aniline solution in acetic acid. Contents of the test tubes painted in bright red color:
Due to the presence of long system of conjugated double bonds this salt has a bright color.
Experiment 8. Qualitative reactions on hexoses.
Reagents: 5% solution of glucose, conc. HCl, 2% water solution of iodine, 5% solution NaOH, Selivanov reagent (resorcinol + conc. H2SO4), 2% solution of glucose, 2% solution of fructose, 20% alcoholic solution of diphenylamine.
A) Formation of levulonic acid from hexoses.
Technique of the experiment. To the 10 drops of glucose 5% solution add 1 ml of the concentrated HCl and boil this mixture on the flame of gas-burner during 1-2 minutes. A liquid here darkles and brown patches are selected.
Aldohexoses under the action of mineral acid along with other products forms a 5-hydroxymethylfurfural:
5-hydroxymethylfurfural is unstable and easily hydrolyzed to levulonic acid:
Fructose forms levulonic acid at the heating with diluted hydrochloric acid. By the action of concentrated acid deep destruction of the molecule takes place.Formation of levuloic acid is confirmed by iodoform reaction.
Cool the mixture and dilute by water (1:10) to get cloudy solution, which is filtered through folded filter. To the transparent yellow filtrate add 1-2 drops of 2% water solution of iodine and then by drops add 5% solution of NaOH to the color disappearance. Cool the mixture. Observe after appearance of the yellow color and feel the characteristic smell of iodoform.
B) Selivanov reaction on ketoses.
Technique of the experiment. To the two test tubes bring 2 drops of Selivanov reagent and then in one test tube put a few drops of 2% solution of fructose, and in the second – glucose. Test tubes heat on the boiling water-bath during 2 minutes. Solution which contains fructose at once paints in red color, and solution which contains only glucose paints in light yellow color. This is due to the fact that hexoses during heating with hydrochloric acid convert into hydroxymethylfurfural, which gives a colored product of condensation with resorcine. Fructose under investigation becomes hydroxymethylfurfural in 15-20 times faster than glucose. This is due to the different rates of color formation of fructose and glucose solutions and its intensity is different:
C) The quality reaction on fructose with diphenylamine.
Technique of the experiment. To the test tube bring 2 ml of 2 % solution of fructose, 1 ml of 20 % alcoholic solution of diphenylamine and 1 ml of concentrated HCl. The got mixture is heated during 2-3 min. on the boiling water-bath. Content of test tube is painted in an intensive blue color due to the formation of furan derivative with the following structure:
Experiment 9. The reaction of Keller-Killiany (opening of deoxysaccharides).
Reagents: 5% solution iron (II) sulfate, acetic acid ice solution, conc. H2SO4, deoxyribose.
Technique of the experiment. To the test tube bring 1 ml of 5% solution of iron (II) sulfate, 1 ml ice acetic acid and few crystals of deoxyribose. In homogeneous solution on a wall of tube add 2 ml of the obtained by mixing 1 ml of 5 % aqueous solution of iron (II) sulfate and 1 ml of concentrated sulfate acid.
Observe the blue color of the upper liquid layer.
This reaction is specific for free deoxysaccharides, or if they take extreme position in the glycosides molecule.
Experimental task
1. Three test tubes contain glucose, fructose and mannose. How identify each monosaccharides? Conduct laboratory experiments.
2. Four test tubes contain glucose, formaldehyde, acetone and mannose. Propose ways of those substances identification.
Synthesis of organic compounds
b–penthaacethylglucose
Scheme of the synthesis:
Method of synthesis
Reagents: waterless glucose – 0.5 g, acetic anhydride – 2 ml, sodium acetate – 0.5g.
Equipment and materials: Thick-walled test tube, air refrigerator, chlorocalcium tube, water-bath.
Experiment conduct under of drawing cupboard.
Technique of the experiment. In the dry test-tube of device mix up 0,5 g of waterless glucose with 0,5 g of waterless sodium acetate. To the got mixture add 2 ml of acetyloxide (Carefully! Acetyloxide gives burns!). A test tube with reactionary mixture is closed by air cover from refrigerator and heat on a boiling water-bath or spirit-lamp (the gas burner) to the complete dissolution of glucose crystals. The got homogeneous mass is cooled and outpour in the test tube with 5-6 ml of water.Crystals of b-pentaacetylglucose fall out.
Individual Students Program.
1. Monosaccharides, their structure, classification, nomenclature, medical and biological significance.
2. Stereoiosomery: D-and L-stereochemical rows, enantiomers, diastereomers, epimers. Fischer projection formulas, Colley-Tollen’s formulas, Haworth formulas. Chirality.
3. Carbonyl-endiol and cycle-oxo-(annular-chain) monosaccharides tautomery, phenomenon of mutarotation. Cyclic monosaccharides’ hemiacetales (pyranoses, furanoses), α– and β-–anomers.
4. Conformational structure of pyranose cycle.
5. Methods of monosaccharides obtaining.
6. Reactivity of monosaccharides. Ethers and esters of monosaccharides, O-, N-, S-glycosides and their hydrolysis.
7. Reduction properties of monosaccharides: obtaining of polyatomic alcohols aldonic, aldaric (sugar) and uronic acids.
8. Qualitative reactions of monosaccharides: Felling, Trommer, Selivanov, Bial samples, formation of ozazones.
9. Derivatives of monosaccharides – aminoalcohols, ascorbic acid (vitamin C).
10. The main representatives of pentoses and hexoses, physical methods of their identification.
Seminar discussion of theoretical issues (1230 – 1400 hour).
Test evaluation and situational tasks.
Home task. 1, 2.
1. Write the structural formulas of Haworth for the next compounds: 1) α-D-galactopyranose; 2) β-D-ribofuranose; 3) α-D-fructofuranose; 4) β-D-glucofuranose; 5) methyl- β-D-fructopyronoside; 6) ethyl-α-D-manofuranoside; 7) L-glucose; 8) β-D-manopyranose; 9) L-desoxyribose; 10) L-fructose.
2. Give the name of these connections:
3. Write the reaction of the glucose transformation in such compounds: 1) D-mannose; 2) D-arabinose; 3) ethyl-b-D-glucopyranose; 4) hexane; 5) D-sorbose; 6) pentaacetyl-a-D-glucopyranose.
4. What phenomenon is called mutarotation? Point scheme of cyclo-oxo-tautomeric transformations of these compounds: 1) D-glucose, 2) D-ribose, 3) D-fructose. Name tautomeric forms.
5. Write the formulas of D-galactose furanose and pyranose forms. Write the reaction of this monosaccharide with such compounds:
Br2 (H2O); 2) conc. HNO3; 3) NaBH4; 4) [Ag(NH3)2]OH; 5) C6H5NHNH2; 6) C2H5OH (HCl(gas)); 7) Felling reagent; 8) H2NOH; 9)excess. Of CH3I or (CH3)2SO4; 10) excess of (CH3CO)2O.
6. Write reaction scheme of D-ribose and D-galactose reduction by sodium borohydride and oxidation in different conditions. Name the extracted substances. Which of the oxidation products are optically active, and which are not optically active?
7. Why fructose foes give reaction of “silver mirror”. What happens with fructose in ammonium medium and how this process is called? Provide appropriate schemes of transformations. Write schemes of reactions of D-fructose with such reagents: a) methyl iodide; b) benzoylchloride; c) propanol (HCl); d) acetic anhydride; e) sodium borohydride; f) hydrocyanic acid; g) hydroxylamine. What products can be expected in the latter case? Will they show optical activity?
8. Explain whether through the reaction of ozazones formation to distinguish D-mannose, D-glucose and D-fructose. Write the schemes of chemical reactions.
9. Carry out the following transformations. Name the intermediate and eventual products of reaction:
D-ribose–????
D–fructose –???
D-glucose® D-sorbite®L-sorbose®2-keto-L-gulonic acid®ascorbic acid
10. What reagents should be used to carry out the following transformations?
11. Write the chemical reactions that prove the presence in D-glucose and D-fructose molecule of: 1) the normal chain of carbon atoms; 2) aldehyde and keto-group; 3) hydroxyl groups, 4) glycosidic (hemiacetal) hydroxyl.
12. Carry out the following scheme of transformations and name the products of reaction:
11. Write the reaction of a – D-glucopyranose interaction with ethanol in the presence of conc. H2SO4 (in a waterless medium). Name the products of reactions. To which class of compounds include the reaction product? Why the reaction is carried out in complete absence of water?
12. What happens with pentamethylglucose and pentaacetylglucose at the heating with diluted sulfate acid? Write the scheme of reactions.
13. Which of the following monosaccharides does belong to hexoses?
A. Xylose
B. Mannose
C. Arabinose
D. Ribose
E. Lyxose
14. Which of the following monosaccharides does belong to hexoses?
A. Xylose
B. Ribose
C. Arabinose
D. Glucose
E. Lyxose
15. Which of the following monosaccharides does belong to pentoses?
A. Glucose
B. Mannose
C. Arabinose
D. Fructose
E. Galactose
16. Which of the following monosaccharides does belong to pentoses?
A. glucose
B. mannose
C. galactose
D. ribose
E. fructose
Correct answers of test evaluations and situational tasks:
13. B; 14. D; 15.C;16 D.
Student should know:
– structure, classification, nomenclature, isomery, methods of getting and chemical properties of monosaccharides.
Student should be able to:
– on the basis of functional groups to attribute matters to the certain class of organic compounds;
– to give the names organic connections with the help of rational and international (IUPAC) top- level systems;
– to conduct reactions which characterize of chemical properties of monosaccharides.
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).
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/zag_him/classes_stud/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lesson_22.Carbohydrates Monosaccharides.
9. http://intranet.tdmu.edu.ua/data/kafedra/internal/zag_him/presentations/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lecture_14.Carbohydrates. Monosacchrides.
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
