Methodical Instruction for Students of the 2 Course pharmaceutical Faculty
LESSON № 10 (PRACTICAL – 6 HOURS)
Themes: Alcohols and their thioanalogs. Small practicum.
Aim: To learn: the nomenclature, isomery, methods of extraction, physical and chemical properties of mono-, di- and trihydroxyl alcohols and their thioanalogs, usage in the pharmacy.
Professional orientation of students:
All alcohols, а principle, can be divided into two broad categories i.е. aliphatic alcohols und aromatic alcohols.
As already mentioned, alcohols containing one ОН group per molecule are called monohydric alcohols. These are further classified as primary (1′), secondary (2′), and tertiary (3′) according as the ОН group is attached to primary, secondary and tertiary carbon atoms respectively.
Monohydric alcohols are characterized by structural, geometrical and optical isomery. Structural isomery depends on different structure of carbon chain and different locations of –OH group.
Only unsaturated monohydroxy alcohols are characterized by geometrical isomery. Optical isomery is characteristic for alcohols which have asymmetric carbon atom in their structure.
Methodology of Practical Class (900-1200).
Experiment 1. Solubility of alcohols, reactions of their water solutions.
Reagents: methyl alcohol, ethyl alcohol, propyl alcohol, isoamyl alcohol, ethylene glycol (ethylene alcohol), glycerin, litmus paper.
Technique of experiment. In the 6 test-tubes bring 5 ml of distil water and add about 2 ml of alcohols (methyl alcohol, ethyl alcohol, propyl alcohol, isoamyl alcohol, ethylene glycol, glycerin). Mix the components in each test-tube. Determine the acidity of water solutions of alcohols using litmus paper.
What do you see?
Determine the pH of medium by neutral litmus paper. Immerse electrodes in the solution to determine electric conduction, also determine if water solutions of thesealcohols conduct electric current. Explain the answer.
Experiment 2. The determination of water in alcohol. Absolutization of alcohol.
Reagents: ethyl alcohol, waterless CuSO4.
Technique of experiment. Bring in a test-tube 5 ml of ethyl alcohol and add few crystals of waterless CuSO4. Slightly heat the test–tube, mix its content.
What changes do you see? Explain the answer.
Filter the mixture (absolute alcohol) and keep it to the next experiment.
Experiment 3. The extraction and hydrolysis of sodium ethylate.
Reagents: absolute ethyl alcohol (from previous experiment), metallic sodium, phenolphthalein.
Equipment and materials: scalpel, pincer, filter paper, test-tube with cork and gas-pipeline.
Technique of experiment. Bring in a test-tube 5 ml of absolute ethyl alcohol and add a piece of metallic sodium. Close the test-tube by cork with gas-pipeline tube. Burn the gas that evaporates. After the interaction of all metallic sodium open the test-tube and heat the mixture. White precipitate of sodium ethylate forms. Solve it in water and add few drops of phenolphthalein.
What do you see? Write the equations of reactions.
Experiment 4. The dehydration of ethyl alcohol.
Reagents: ethyl alcohol, H2SO4 (concentrated solution), Al2O3, bromine water, 1% solution KMnO4.
Technique of experiment. Bring in a test-tube 8 drops of concentrated H2SO4, 4 drops of ethyl alcohol, several crystals of Al2O3 and close the test-tube by cork with gas-pipeline tube. Deep the end of gas-pipeline tube into the test-tube with 5 drops of bromine water. Heat the mixture. When the color of bromine water disappears, deep the end of gas-pipeline tube into the test-tube with 1 drop of 1% KMnO4 in 3 ml of water. Continue heating; observe that color of solution changes. Burn the gas that evaporates and determine the color of the flame.
Write the equations of reactions.
Experiment 5. The extraction of diethyl ether.
Reagents: ethyl alcohol, H2SO4 (concentrated solution).
Technique of experiment. In a dry test-tube bring the mixture of ethyl alcohol and concentrated H2SO4 (1:1). Heat it very carefully to the boiling. After heating add 5-10 drops of ethyl alcohol. Diethyl ether can be determinate by smelling.
Write the equations of reactions.
Experiment 6. The extraction of complex ethers.
Reagents: ethyl alcohol, H2SO4 (concentrated solution), waterless sodium acetate, boric acid.
Technique of experiment.
a) The extraction of ethyl ether of boric acid. In a dry test-tube bring 1 g boric acid and heat it. When all crystals disappear, cool the test-tube. Add 2 ml of ethyl alcohol and 1 ml concentrated H2SO4. Close the test-tube by cork with gas-pipeline tube. Heat the mixture very carefully to the boiling. Ethyl ether of boric acid (triethylborate) (С2Н5О)3В evaporates, because it boils at the temperature of 117,3°С. Burn the gas near the opening of gas-pipeline tube. The gas burns with greenish flame. You can use also a copper wire.
2Н3ВО3 
В2О3 + 3Н2О
В2О3 + 6С2Н5ОН ® 2(С2Н5О)3В + 3Н2О
b) The extraction of ethyl acetate. In a dry test-tube bring 2 ml of waterless sodium acetate and add 3 drops of ethyl alcohol. Add 2 drops of concentrated H2SO4 and heat the mixture very carefully. The smell of ethyl acetate appears.
Write the equations of reactions.
Experiment 7. The contraction of alcohol (demonstration experiment).
Reagents: ethyl alcohol, distil water.
Technique of experiment. In a measuring cylinder (50 ml) bring 25 ml of ethyl alcohol and add 25 ml of distil water. Mix the mixture. What volume will have the mixture after 10 min.?
Experiment 8. The reactions of alcohols with Cu(OH)2.
Reagents: ethyl alcohol, ethylene glycol, glycerin, 5% solution CuSO4, 5% solution NaOH.
Technique of experiment. In 3 test-tubes bring 1 ml of 5% solution CuSO4 and 1 ml of 5% solution NaOH. Cu(OH)2 forms. Then in the first test-tube add 0,5 ml of ethyl alcohol. In the second test-tube add 0,5 ml of ethylene glycol. In the third test-tube add 0,5 ml of glycerin. Mix the mixtures.
What do you see? Make a conclusion about the acidic properties of ethanol, ethylene glycol and glycerin.
Reaction with copper (II) hydroxide is the qualitative reaction on polyatomic alcohols.
Experiment 9. Formation of iodoform from acohol.
Reagents: isopropyl alcohol, solution of I2 in KI, 10% solution of NaOH.
This experiment can be executed only with alcohols that content methyl group at the primary or secondary carbon atoms, which connected with OH–group. For example:
Technique of experiment. Bring in a test-tube 2-3 drops of isopropyl alcohol, 3 drops of I2 in KI solution and 1-2 drops of 10% solution NaOH to the disappearing of brown color. Heat the mixture to light-yellow color. After some time yellow precipitate with stable characteristic smell forms. It is necessary that inreaction mixture was not excess of alkali, which hydrolyzes iodoform.
The scheme of reaction:
a) Reaction of I2 with alkali:
I2 + 2NaOH = NaI + NaOI+ H2O
b) Oxidation of alcohol:
c) Substitution of hydrogen atoms in the radical on halogen:
d) Destroying of the formed compound in the presence of alkali:
Experiment 10. The reactions of alcohols with ZnCl2 in HCl (Lucas test).
Reagents: ethyl alcohol, isopropyl alcohol, tret-butyl alcohol, Lucas reagent.
Technique of experiment. In the first test-tube bring 3-4 drops of ethyl alcohol, in the second test-tube bring 3-4 drops of isopropyl alcohol and in the third test-tube bring 3-4 drops of tret-butyl alcohol. In all test-tubes add 6 drops of Lucas reagent. Shake the mixtures very well.
What do you see during 5 minutes?
Primary, secondary and tertiary alcohols react with Lucas reagent with different speed (formation of chloroalkanes). This peculiarity is used for the identification of different alcohols. Tertiary alcohols react at once after the adding of Lucas reagent. The layer of chloroalkane forms, which is not dissolve in water. Secondary alcohols react after 5 minutes and the drops of chloroalkane forms, solution becomes muddy. Primary alcohols do not react with Lucas reagent.
Tertiary and secondary alcohols can be distinguished by the sample with concentrated chloride acid in the absence of zinc chloride. In these conditions tertiaryalcohols will react during 3-5 minutes, secondary – don’t react.
Experiment 11. The oxidation of alcohols by chromic mixture.
Reagents: ethyl alcohol, chromic mixture, fuchsine sulfate acid.
Technique of experiment. In a test-tube bring 2-3 ml of chromic mixture and shaking add 0,5 ml of ethyl alcohol by drops. The color of mixture changes. The smell of apple appears (it is acetic aldehyde). In a test-tube with 3 drops of fuchsine sulfate acid bring 1 drop of the formed acetic aldehyde. The pink-violet color means that it is aldehyde (the colour reaction on aldehyde group).
Write the equations of reactions.
Experiment 12. The extraction of acroleine from glycerin (demonstration experiment).
Reagents: glycerin, waterless potassium hydrosulfate, fuchsine sulfate acid.
This reaction is qualitative reaction to glycerin.
Technique of experiment. In a dry test-tube bring few crystals of the waterless potassium hydrosulfate and 2-3 drops of glycerin. Heat the mixture to the browning color of the mixture and appearing of the vapors of aldehyde – acroleine with sharp smell (Ventilation cupboard!). Bring to the opening of the test-tube the piece of filter paper wetted by fuchsine sulfate acid. The red color appears (qualitative reaction on aldehydes).
Write the equations of reactions.
Experiment 13. Interaction of the vicinal polyols with iodic acid.
Reagents: iodic acid, conc. nitrate acid, ethylene glycol or glycerin, 5 % silver nitrate solution.
Technique of experiment. In the tube mix 2 ml of iodic acid and 1 drop (not more) of conc. nitrate acid. To the obtained solution add 1 drop of ethylene glycolor glycerin. Content of the tube shake vigorously during 10-15 seconds. Vicinal polyols oxidize and iodic acid reduces to iodate acid:
To the obtained solution in the tube add 2 drops of 5% silver nitrate solution and observe formation of silver iodate white color:
This reaction can be used to identify vicinal polyols. If the sample is negative it is possible secretion of brown precipitate, which dissolves at the shaking.
Experiment 14. Obtaining of ethylmercaptane.
Reagents: ethyl alcohol, ethylbromide, 20% solution of NaHS.
Technique of experiment. In a test-tube bring 1 ml of 20% solution of sodium hydrosulphide, 1 ml of ethanol and 4 drops of ethylbromide. The content of the test-tube is heated and feel characteristic smell of mercaptane:
C2H5Br + NaHS ® C2H5SH + NaBr
ethylmercaptane
Thioalcohols in the comparison with appropriate alcohols are almost not associated and more volatile.
Sharp unpleasant smell is detected at the very low concentrations (up to 2·10–9 mg/l). After the end of experiments all tubes are worked up by the strong oxidants(chromic mixture or alkali solution of potassium permanganate) to destroy the tracks of mercaptane.
Obtained mercaptane is used for the next experiments.
Experiment 15. Formation of lead (II) mercaptide.
Reagents: ethylmercaptane, saturated solution of lead (II) acetate.
Technique of experiment. In a test-tube bring 3 drops of alcohol solution of ethylmercaptane (experiment 14), 3 drops of saturated alcoholic solution of lead (II) acetate. Observe the formation of the yellow precipitate of lead (II) mercaptide. This reaction is used for the identification of mercaptanes.
2C2H5SH + (CH3COO)2Pb ® H5C2–S–Pb–S–C2H5 ¯ + 2CH3COOH
lead (II) ethylmercaptane
Experiment 16. Interaction ethylmercaptane with sodium nitroprusside.
Reagents: ethylmercaptane, 10% solution of potassium hydroxide, 1% solution of sodium nitroprusside
Technique of experiment. In a test-tube bring 1 ml of alcohol solution ethylmercaptane, 1 ml of 10% solution of potassium hydroxide and 3-5 drops of 1% solution of sodium nitroprusside. At the shaking of test-tube observe the appearance of purple-red colour, caused by the formation of complex compound.
Experiment 17. Interaction of ethylmercaptane with bromine.
Reagents: ethylmercaptane, C2H5OH, solution of bromine in CCl4
Technique of experiment. In a test-tube bring 10 mg of ethylmercaptane, 1 ml of ethanol and add by drops solution of bromine in CCl4. Observed that bromine water becomes colourless. This reaction is used for the identification of mercaptanes.
2C2H5SH + Br2 ® H5C2–S–S–C2H5 + 2HBr
diethylsulfide
Basic concepts of theme
Composition – Structure – Properties
Hydroxi-group
Zajtsev rule
Intermolecular dehydration
Intramolecular dehydration
Contraction
Monohydroxyl alcohols
Dihydroxyl alcohols
Trihydroxyl alcohols
Primary alcohols
Secondary alcohols
Tertiary alcohols
Thioalcohols
Aminoalcohols
Individual Students Program.
1. Classification of alcohols by the number of hydroxyl groups and nature of the hydrocarbon radical.
2. Isomery and nomenclature of alcohols.
3. Methods of obtaining of mono-, di– and triatomic alcohols.
4. Acid–basic properties of alcohols. Intermolecular association of alcohols, its influence on the physical and spectral characteristics.
5. Chemical properties of mono-, di– and triatomic alcohols: formation of alcoholates, simple and difficult ethers, intramolecular dehydration, substitution of hydroxyl groups on halogen, oxidation.
6. Aminoalcohols. Nomenclature. Methods of obtaining. Chemical properties.
7. Identification of alcohols.
8. Some representatives, usage.
9. Classification, nomenclature and isomery of thiols. Methods of obtaining.
10. Physical and chemical properties:
a. formation of thiolates (mercaptides);
b. interaction of thiols with alkenes;
c. alkylation, acylation;
d. oxidation.
11. Some representatives, usage.
Seminar discussion of theoretical issues (1230 – 1400 hour).
Test evaluation and situational tasks.
Home task: 1, 3, 8, 10.
1. Name the following alcohols by the international and rational nomenclatures:
2. Write the structural formulas of isomers of С5Н11ОН. Name them by international and rational nomenclatures. Specify which alcohol among these isomers is theprimary, secondary or tertiary. Which of the alcohols have optical activity?
3. Write the structural formulas of the following alcohols: isoamyl alcohol; tetramrthyleneglycol; tret–butyl alcohol; butanol-2; propanediol-1,2; 2,2-dimethylpropanol-1; 2-hydroxymethylpropanediol-1,3; 2,3-dimethylpentanetriol-1,3,5.
4. Obtain propyl alcohol from methyl alcohol and inorganic reagents.
5. Write the scheme of glycerin obtaining from propylene. Name compounds which will be obtained at the action of acetic and nitrate acids on the glycerin.
6. What alcohols will form at the alkali hydrolysis of phtor–bromobutyl, 3-chloro-2-methylbutane.
7. To the 2-methylpropanol-2 potassium permanganate solution was added. Write the reaction equation and show oxidation–reduction process.
8. Write the equations of reactions of the interaction of n–propyl alcohol and ethylene glycol with: 1) Na; 2) C2H5MgJ; 3) HCl (gas); 4) PCl5 or SOCl2. Name theproducts. Specify in which reactions alcohols have acidic or basic properties.
9. On the glycerin example characterize intramolecular dehydration. Explain Zaicev rule. Write mechanisms of reactions; name the products.
10. What alcohols will form at the action of water solution of alkali on 1-chloro-3-methylbutane, isopropyl iodine? Show the mechanism of reactions.
11. What products and in which quantity will form at heating of 50 g of ethyl alcohol and 100 g of sodium bromide in the presence of sulfate acid. What compoundwas taken in excess?
12. At the interaction of metallic sodium taken in excess with 3,7 g of saturated monoatomic alcohol stand out 0,56 l of hydrogen. Determine molecular weight of alcohol and write its formula.
13. From the appropriate halogenderivative and alcoholate obtain diethyl ether.
14. Obtain from the appropriate halogenalkanes ethylmercaptane, dimethylsulfide and methylethylsulfide. Name these compounds by international nomenclature. Write the reactions of dimethylsulfide with the following reagents: CH3J; H2O2 (CH3COOH, 200C); H2O2 (CH3COOH, boiling)
15. Make the transformations and name the products of reactions:
а) CH3–CH=CH2 № 1 № 2 № 3 № 4 № 5 № 6;
b) CHºCH № 1 № 2 № 3 № 4 № 5 № 6 № 7;
c) CH2=CH2 № 1 № 2 № 3 № 4 № 5;
d) CH3–CH2–CH2–Br № 1 № 2 № 3 № 4 № 5.
16. Write the schemes of reactions propanthiol-2 with such reagents: 1) Na; 2) KOH; 3) HgO; 4) CH3COOH, H+; 5) [O] KMnO4; 6) [O] H2O2.
17. Compare acidic properties of ethanethiol and ethanol. Explain the answer.
18. Make the transformations and name reaction products:
а) CH2=CH2 № 1 № 2 № 3 № 4 № 5;
b) propene № 1 № 2 № 3 № 4 + № 5;
c) ethylmercaptan № 1 № 2 № 3 № 4;
d) СН3–СН=СН2 № 1 № 2 № 3.
19. Write the scheme of obtaining of butanethiol from the appropriate halogenalkane. Specify the substrate and nucleophillic reagent in this reaction. Whathalogenalkane mainly use in this reaction?
20. What reactions can be used to distinguish thioalcohols from alcohols? Write the scheme of ethanethiol oxidation and name the products. Synthesize diethylsulfide and ethanesulfoacid from ethanethiol.
21. Which of the alcohols – pentanol-1 or 2-methylbutanol-2 – easily gives the reaction of intramolecular dehydration under the action of sulfate acid? Point theschemes of reactions. What properties – nucleophillic or basic has alcohol in these reactions?
22. What reactions can be used to distinguish ethanol from glycerin? Write the schemes of reactions.
23. Write the scheme of reactions of qualitative determination of polyatomic alcohols.
24. Write the following transformations, name the reaction products:
25. Write the following transformations, name the reaction products:
26. Which of the alcohols – butanol–2 or 2-methylbutanol-2 – easily gives the reaction of intramolecular dehydration under the action of sulfate acid? Point the schemesof reactions. What properties – nucleophillic or basic has alcohol in these reactions?
27. Choose the correct name of the following compound.
B. 2-propynylethanol
C. pentyn-2-ol-5
D. 5-hydroxypentyne-2
E. pentyne-3-ol-1
F. pentyne-3-ol-5
28. Which of the following reactions can be used for α-glycols identification?
A. Lucas test (ZnCl2 + HCl conc.)
B. iodoformic test (I2 + NaOH)
C. periodic acid oxidation (HIO4)
D. indophenol test (Br2; NH3)
E. interaction with copper hydroxide (Cu(OH)2)
29. In which of the following reactions ethylene glycol displays its acidic properties.
A.
B.
C.
D.
E.
30. Which of the following reactions can be used to distinguish propyl alcohol from isopropyl alcohol?
A. iodoformic test (I2 + NaOH)
B. reaction of dehydration
C. oxidation (CrO3; H+)
D. Lucas test (ZnCl2; HCl conc.)
E. interaction with copper (ІІ) hydroxide
31. What is the end-product of the following reaction?
- CH3 –O–CH3
Correct answers of test evaluations and situational tasks:
27.D, 28.C, E 29.B, E 30. A, C, D.31. C.
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:
– the structure, nomenclature, isomery, methods of extraction and chemical properties of alcohols, thioalcohols and aminoalcohols .
Student should be able to:
– to be able to do the chemical reactions which characterise the chemical properties of alcohols, thioalcohols and aminoalcohols.
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_him2/classes_stud/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lesson_10.Reactionary ability of alcohols.
9. http://intranet.tdmu.edu.ua/data/kafedra/internal/zag_him/presentations/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lecture_06.Alcohols. Phenols. Ethers.
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
