Methodical Instruction for Students of the 2 Course pharmaceutical Faculty
LESSON № 14 (PRACTICAL – 6 HOURS)
Themes: 1. Functional derivates of the carboxylic acids. Small practicum.
2.Heterofunctional carboxylic acids. Small practicum.
Aim: to learn: the structure, nomenclature, chemical properties, the practical significance of heterofunctional carboxylic acids; functional derivatives of carboxylic acids.
Professional orientation of students:
Heterocyclic compounds are cyclic compounds with one or more ring atoms that are not carbon (that are, hetero atoms). Although heterocycles are known that incorporate many different elements into cyclic structures (for example, N, О, S, В, Al, Si, P, Sn, As, Cu), we shall consider only some of the more common systems in which the hetero atom is N, О, or S. Heterocycles are conveniently grouped into two classes, nonaromatic and aromatic. The nonaromatic compounds have physical and chemical properties that are typical of the particular hetero atom. Thus, tetrahydrofurane and 1,4-dioxane are typical ethers, whereas 1,3,5-trioxane behaves as anacetal.
Methodology of practical class (900-1200)
Experiment 1. The reactions of acetamide.
Reagents: acetamide (10% solution), NaOH (5% solution), HCl (concentrated), H2SO4 (10% solution), hydroxylamine hydrochloride, FeCl3 (1% solution).
Technique of experiment.
a) In a test-tube bring 1 ml of 10% acetamide, add 10 drops of 5% NaOH. Heat the mixture. What’s happening? How to detect the formed gas?
Write the equations of reactions.
b) In a test-tube bring 1 ml of acetamide (10% solution) and add 3-4 drops of H2SO4 (10% solution). The mixture is boiled.
Write the equations of reactions.
c) In a test-tube bring several crystals of hydroxylamine hydrochloride, add 10 drops of water and add 3 drops of 10% acetamide. The mixture is boiled for 3 min.What’s happening? Write the reactions.
After cooling add 2 ml of FeCl3 (1% solution). What’s happening?
Write the equations of reactions.
Experiment 2. Splitting of acid amides (Hofmann’s regrouping).
Reagents: acetamide (10% solution), NaOH (10% solution), bromine water, CuSO4 (2% solution).
Technique of experiment. In a test-tube bring 1 ml of acetamide (10% solution) and add 10 drops of water. Shake the mixture and add 5 drops of bromine water and 10 drops of NaOH (10% solution). Close the test-tube by a cork with gas-pipeline. Deep the end of the gas-pipeline tube into the test-tube with 1 ml of water. Heat the mixture in the first test-tube during 3-5 minutes. What substances are formed?
Write the equations of reactions.
The presence of amine in a reaction mixture confirmed with a few drops of 2% aqueous solution of copper (II) sulfate:
2[СH3NH3]+OH– + CuSO4 ® (СH3NH3)2SO4 + Cu(OH)2 ¯
Control questions:
1. Point the schemes of acidic and alkaline hydrolysis of acetamide.
2. Write the scheme of qualitative reaction on hydroxamic acid.
Experiment 3. Extraction and properties of pyruvic acid.
Reagents: 5% solution of lactic acid, 10% solution of sodium carbonate, 1% solution of potassium permanganate, 0,5% solution of sodium nitroprusside, saturated solution of sodium hydrosulfite, 5% solution of pyruvic acid, 5 % solution of propionic acid, a universal indicator paper with the scale of pH, phenylhydrazinehydrochloride, sodium acetate.
Technique of experiment. a) obtaining of pyruvic acid. In test tube bring 2 ml of 5% solution of lactic acid and add by drops during the shaking 10% solution of sodium carbonate to the neutral reaction on litmus. Then fill up 1 ml of 1% potassium permanganate solution and the mixture is heated to boiling:
After the cooling the solution is filtered and in the filtrate ketoacid is determined by the reaction with sodium hydrosulfite or sodium nitroprusside. What do you observe?
b) comparison of the force of pyruvic and propionic acids. On a paper strip of the universal indicator drops put 5% aqueous solution of pyruvic acid and 5% aqueous solution of propionic acid. With the scale determine the pH of these solutions.
Pyruvic acid is much stronger than propionic. Increasing of acidity caused by the influence of pyruvic acid carbonyl group:
c) extraction pyruvic acid phenylhydrazine. In a test tube bring 1 ml of 5% aqueous solution of pyruvic acid, 0,1 g of phenylhydrazine and 0,1 g of sodium acetate. The obtained reaction mixture is heated on the boiling water bath during 15-20 min. After cooling a yellow precipitate of pyruvic acid phenylhydrazine falls down. Formation of phenylhydrazine confirms that the pyruvic acid has carbonyl group.
Experiment 4. Properties of glyoxylic acid.
Reagents: 5%solution of glyoxilic acid, 5% solution of sodium hydrocarbonate, 5% solution of calcium chloride, 1% silver nitrate solution, 5% solution of ammonium hydroxide.
Technique of experiment. a) formation of glyoxylic acid salts. Bring in two test-tubes by 1 ml of 5% solution of glyoxylic acid. Then in one of them add by drops 1 ml of 5% solution of sodium hydrocarbonate, and in another – 0,5 ml of 5% solution of calcium chloride. Observe as during the interaction of glyoxylic acid with sodium hydrocarbonates blisters of carbon (IV) oxide are actively allocated, and with calcium chloride glyoxylic acid forms hardly soluble white salt sediment which falls in the form of sediment:
b) aldehyde properties gluoxylic acid. In the well defatted test-tube mixed 1 ml of 5% solution of glyoxylic acid with 1 ml of 5% solution of sodium hydrocarbonate. After the completing allocation of carbon dioxide, to the obtained sodium glyoxylate add 4-5 drops of ammonium solution of silver oxide. The obtained reaction mixture is not shacked and put in the hot water-bath. After 5-6 min. observe the formation of metallic silver precipitate on the walls of the tube (“silver mirror”). This indicates the presence of aldehyde group in glyoxylic acid.
Experiment 5. Properties and proof of the structure of “acetoacetic ester”.
Reagents: acetoacetic ester, 2 N sodium hydroxide solution, 1% alcoholic solution of phenolphthalein, metallic sodium, saturated bromine water solution, 5% solution of iron (III) chloride.
Technique of experiment. a) detection of “acetoacetic ester”acidic properties. In the test tube bring 3 ml of water and by drops add 1% phenolphthalein solution and 2 N sodium hydroxide solution. The obtained solution is painted in crimson color. To the obtained reaction mixture add 2-3 drops of “acetoacetic ester”. Observe as the color of phenolphthalein disappears. Thus, “acetoacetic ester” has acidic properties and neutralizes the alkali.
b) interaction of “acetoacetic ester” with metallic sodium. In a dry test tube bring 1 ml of “acetoacetic ester” and a small piece (size of a quarter of the pea) of the purified from the oxide film and dried with filter paper from kerosene metallic sodium. Test-tube is closed by a cork with gas-pipeline tube and fixed on a tripod.Observe as the sodium is actively cooperating with acetoacetic esters and gaseous products (hydrogen) evaporate. After 1 min. from the beginning of reaction gas, which evaporates from the reaction mixture, set fire near the gas-pipeline tube. Gas begins to burn with sound, characteristic for burning of hydrogen mixture with air (roaring gas) and slightly burning blue flame characteristic for burning hydrogen appears. During the reaction “sodium acetoacetic ester” forms, which upon the cooling of the reaction mixture precipitates. (Be careful! After the end of the experiment in the test-tube should not be pieces of metallic sodium.)
c) detection of the double bond in acetoacetic ester. In the test-tube bring 10 drops of “acetoacetic ester” and at the intensive mixing 10 drops of the saturated bromine water. Observe the discoloration of bromine water, indicating unsaturation “acetoacetic ester”.
d) detection of the enol form of “acetoacetic ester”. In the test-tube mixe 10 drops of acetoacetic ester with 10 drops of 5% solution of iron (III) chloride. Observed appearance of the purple color, caused by the formation of complex salt (enol form) of “acetoacetic ester” with Fe3+ ions:
Enol form of “acetoacetic ester” is stable due to formation of intramolecular hydrogen bond:
e) to prove the presence of equilibrium between the tautomeric forms (keto-form and enol form) of acetoacetic ester. In test-tube mix 1 ml of water, 5 drops of “acetoacetic ester” and 2-3 drops of 5% solution of iron (III) chloride. Observe as reaction mixture becomes purple, indicating the presence of enol form of “acetoacetic ester”. To the obtained colored reaction mixture add a few drops of bromine water. Violet color of the solution disappears, but after a few seconds, appears again. When the purple color returns again, to the reaction mixture again add a few drops of bromine water. Purple color at first quickly disappears, but quickly restores. The phenomenon that was observed can be explained by the existence of two tautomeric forms of “acetoacetic ester”, which always exist together in a state of dynamic equilibrium:
Depending on the nature of the chemical reagent one of these forms will enter into a chemical reaction. This leads to the violation of dynamic equilibrium. To restore the balance, the second tautomeric form isomerizes in the one that entered in the reaction. Thus, the appearance of purple color at the adding to “acetoacetic ester” solution of iron (III) chloride indicates the presence in “acetoacetic ester”enol form (enol hydroxyl group). When you add bromine water purple color of the solution disappears as the bromine attached to the double bond and hydroxyl group loses enolic character:
Bromine links the enol form and violates the dynamic equilibrium and therefore part of the keto-form of “acetoacetic ester”, which is entered in the reaction to restore equilibrium, isomerizes in enol form. Purple coloration appears again.
Monobromacetoacetic ester, which contains an active (mobile) hydrogen atom, also can isomerize in enol form:
Adding of bromine water again will cause the disappearance of purple color, which in a few seconds, appears again. The process can take up to complete substitution of active hydrogen atoms of “acetoacetic ester” on bromine. Formation of dibromoacetoacetic ester takes place that is not capable to tautomeric transformations:
Is the keto-enol tautomerism character for acetylacetone, acetonylacetone, ethyl ester of propionic acid? Explain the answer.
f) keto-splitting of “acetoacetic ester. In the test tube bring 1 ml of “acetoacetic ester” and 2 ml of 10% sulfate acid. In the obtained mixture a few boiling stones is added. Tubes with a reaction mixture is closed by cork with gas-pipeline tube and fixed on a tripod. End of the gas-pipeline tube is immersed in a test tube with 2 ml of lime (barite) water. Reaction mixture is gently heated to the boiling. There is hydrolysis of “acetoacetic ester” and unstable acetoacetic acid forms, which easilydecarboxylates. Carbon (IV) oxide causes a clouding of lime (barite) water. In addition to carbon (IV) oxide at the decarboxylation of acetoacetic acid ethanol and acetone produced. To detect them end of the gas-pipeline tube is immersed into the receiver test-tube with 1-2 ml of water, which is cooled with ice water. Continue to heat the reaction mixture. Drive away in a receiver test tube 5-6 drops of liquid product. In the obtained solution ethanol and acetone can be detected by iodoform test.
Control questions:
1. Write the scheme of tautomeric transformations of acetoacetic ester. What structural fragment causes the appearance of characteristic coloration with a iron (III) chloride solution?
2. Write the scheme of acidic and ketone decomposition of acetoacetic ester. Specify the conditions of reactions.
3. What chemical reactions can be used to detect the products acetoacetic ester decomposition?
Experiment 6. Proving of the structure of lactic acid.
Reagents: lactic acid, H2SO4 conc., Lughole solution 10% NaOH.
A. In a dry test tube contained 0,5 ml of lactic acid and gently add 0,5 ml of concentrated sulfuric acid. Close tube opening by cork with gas-pipeline tube. The solution is heated gently in a flame. The liquid in the test tube becomes dark and begins to foam. Lactic acid by heating with concentrated sulfuric acid decomposes with producing of acetic aldehyde and formic acid, which decomposes to carbon (II) oxide and water. Burn the gas, which evaporates from the gas-pipeline tube. Observe the blue color of the flame indicating the allocation of carbon (II) oxide:
B. In the test tube contained 1 ml of water, 0,5 ml of concentrated sulfuric acid and 0,5 ml of lactic acid. Tube closed by the cork with gas-pipeline tube, end of this tube immerse in a test tube with 1 ml of iodine in potassium iodide, which previously was bleached by adding of few drops of 10% sodium hydroxide. Tube with lactic acid is heated in a flame torch. During the heating lactic acid decomposes with formation of gaseous acetaldehyde (look experiment A) which at the transmittance through the solution of sodium hypoiodide forms a yellow precipitate (iodoform) with a characteristic odor:
Experiment 7. Proving of the structure of tartaric acid.
Reagents: tartaric acid 15%, КОН 3%, СuSO 4 2%, NaOH 10%.
A. To the test tube add 2 drops of 15% tartaric acid solution and 4 drops of 3% solution of potassium hydroxide. Observe a gradual selection of white crystalline precipitate of acid potassium salt of tartaric acid. This reaction used in analytical practice for the detection of potassium ions:
Upon the further adding to the tube 5-10 drops of 3 % solution of potassium hydroxide precipitate dissolves, soluble salt of potassium tartare formed:
salt solution for experiment B.
B. To the test tube add 4 drops of 2% solution of copper (II) sulfate and 10% solution of sodium hydroxide. Observe the formation of copper (II) hydroxide blue precipitate, which while the adding a solution of potassium tartrate dissolves with formation of helat complex:
Experiment 8. Decomposition of the citric acid under the action of concentrated sulfate acid.
Reagents: citric acid (cr.), H2SO4 conc., lime water, Lughole solution, NaOH 10%.
In a dry test tube bring citric acid to a height of 5 mm and gently add 1 ml of concentrated sulfate acid. Close the tube by the cork with gas-pipeline tube, end of this tube immerse in a test tube with lime water. Why does turbidity appear?
Continue the heating of the initial mixture, end of the gas-pipeline tube is immersed in a test tube with 1 ml of iodine in potassium iodide, which was previously bleached by adding of few drops of 10% solution of sodium hydroxide. Observe the formation of yellow precipitate and feel characteristic smell of iodoform:
When burn the gas that evaporates from the gas-pipeline tube, observe the blue color of the flame, which indicate the allocation of carbon (II) oxide.
Experiment 9. Sublimation and decomposition of salicylic acid.
Reagents: salicylic acid (cr.), lime water.
In a dry test tube bring salicylic acid to a height of 5 mm and heat in a flame torch. Salicylic acid by the heating sublimates as a white efflorescence on the cold walls of the tube. Continue not only heat the bottom of the tube, but the wall above the liquid level to pass a steam of acid through the heated zone. As a result of aciddecarboxylation phenol formed, which can be determined by the characteristic odor:
Carbon (IV) oxide at the transmission through the water forms a white precipitate of calcium carbonate.
Experiment 10. Reactions of salicylic acid.
Reagents: salicylic acid (cr), phenol (cr), NaHCO3 5%, FeCl3 1%, ethanol, bromine water, benzoic acid (cr).
A. In two test-tubes pour 1 ml of 5% solution of sodium hydrocarbonate. In one tube at the tip of a palette-knife add salicylic acid, in the second test-tube – the same amount of phenol. Shake all tubes. In test-tube with salicylic acid observe gas evaporation. In the test-tube with phenol visible changes are not observed. Why?
B. In the test tube in 1 ml of water dissolve few crystals of salicylic acid and add 1 drop of 1% solution of iron (III) chloride. Observe appearance of the intense violet color.
When you add in the test-tube an equal volume of ethanol color of the complex remains, unlike the helat complex of phenol with iron (III) chloride.
C. In two the separate tubes bring a few crystals of salicylic and benzoic acids dissolved them in 5-10 drops of distilled water. Shake these tubes and add 2-3 drops of bromine water. In the test-tube with salicylic acid white precipitate falls:
Bromine water added in excess changes the color of precipitate on light yellow, due to the decarboxylation and the formation of 2,4,6-tribromophenol:
Content of the tube to remove the excess of bromine is gently boiled during 1 minute and observe dissolution of precipitate. 2,4,6-Tribromophenol converts to 2,4,4,6-tetrabromo-2 ,5-cyclohexadiene-1-on.
In pharmaceutical practice this reaction underlies in the base of bromatometric method of salicylic acid determining.
Experiment 11. Hydrolysis of acetylsalicylic acid.
Reagents: aspirin, FeCl 3 1%.
In the test-tube at the tip of a palette-knife bring acetylsalicylic acid and add 2 ml of water. The resulting solution is divided into 2 parts, one of which is boiled for 2-3 minutes, then cooled. Into the each tube add 3 drops of 1% solution iron (III) chloride. Content of the test-tube, subjected to heat, becomes purple, indicating the presence of phenol hydroxyl, which formed as a result of the hydrolysis of acetylsalicylic acid. Write the appropriate reactions.
Basic concepts of theme
Carbocylic group
Hofmann’s splitting
Halogenoacids
Hydroxyacids
Phenoloacids
Acetoacetic ester
Decarboxylation
Salicylic acid
Individual students program.
I. Functional derivatives of carboxylic acids. Control questions:
1. For which classes of organic compounds is characteristic the reaction with salts of copper (II)?
2. Write the scheme of splitting of lactic acid under the action of concentrated sulfate acid at the heating. What chemical reactions can be used to detect the degradation products?
3. Write the scheme of reactions, proving the presence of carboxyl groups in the molecule of tartaric acid and glycol fragment.
4. Compare the solubility of acid and medium salts of tartaric acid.
5. Compare the ratio of phenol and salicylic acid to the action of sodium hydrocarbonate.
6. Point the schemes of reactions, progressing at the cooperation of lactic, tartaric, salicylic acid and aminoacetic with copper (II) hydroxide.
7. Nomenclature, structure, methods of obtaining and physical properties of major functional derivatives of carboxylic acids.
8. Amides. Acid-base properties. Hydrolysis of amides. Hofmann’s splitting of amides.
9. Chemical properties of hydrazides, nitriles and hydroxamic acids.
10. Comparison of acylation properties of carboxylic acids and their functional derivatives.
11. Identification of functional derivatives of carboxylic acids.
12. Some representatives, application.
II. Aldehyde– and ketoacids. Usage of acetoacetic ester in organic synthesis
1. Classification, nomenclature, isomerism and methods of obtaining of oxocarboxylic acids.
2. Peculiarities of chemical properties oxoacids as bifunctional compounds. Mutual influence of functional groups.
3. Decarboxylation of α- and β–oxoacids
4. CH-acidity, tautomerism and dual reactivity of acetoacetic ester. Usage of malonic and acetoacetic ester in organic synthesis.
5. Some representatives of the aldo– and ketoacids and their practical application (glyoxylic, pyruvic, acetoacetic).
III. Halogeno-, oxyacids and their functional derivatives. Phenolocarboxylic acid. Synthesis of derivatives of salicylic acid drugs and PABA
1. Classification, nomenclature, isomerism and methods of obtaining of halogenocarboxylic acids.
2. Dependence of halogenoacids acidic properties of the nature, the number of halogen atoms and their location relative to the carboxyl group.
3. Chemical properties halogenocarboxylic acids. Increased mobility of halogen atom in α-position in aliphatic and ortho-and para-positions in aromatichalogenocarboxylic acids.
4. Nomenclature, isomerism and methods of obtaining of alcohol- and phenoloacids.
5. Chemical properties of hydroxyacids. The ratio of α-, β-and γ–hydroxyacids to the heating. Splitting of α–hydroxyacids.
6. Chemical properties of salicylic acid and obtaining on the basis of its derivatives medical drugs.
Seminar discussion of theoretical issues (1230 – 1400 hour).
Test evaluation and situational tasks.
Home task: 2, 5, 8, 10.
1. Consider the structure of malonic acid. Explain why it and its diethyl ester are CH-acids? What is this condensation of Knevenahel? Write the scheme of interaction of “malonic ester” with the following reagents: а) Н 2 О (Н +; t); b) Br 2 ; c) С 2 Н 5 ОNa (C 2 H 5 OH), then С 2 Н 5 J; d) NaNH 2 (NH 3 ) (liq.).Name the products.
2. Synthesize malonic acid from acetic acid. Obtain “malonic ester” and use it to synthesize following acids: 1) butyric; 2) adipic; 3) ethylsuccinic.
3. Obtain “sodium malonic ester”. Consider its structure. Write schemes of interaction of this ester with following compounds: 1) С 2 H 5 Br; 2) CH 2 J 2; 3) Cl-CH 2 -C(O)CCH3. Hydrolyze and heat the obtained products. Write formulas and name derived acid.
4. Write structural formulas of the following compounds: 1) bromanhydride of propionic acid; 2) ethyl acetate; 3) monohydroxyamide of succinic acid; 4) N, N-diethylethaneamide; 5) acetonitrile; 6) ethylisobutyrate; 7) acetic anhydride; 8), maleic anhydride; 9) butyric acid chloride; 10) acrylonitrile; 11) valeric acidhydrazide.
5. Name these compounds:
6. Write the reaction equations of propanoyl chloride with the following reagents: а) H 2 O (NaOH); b) C 2 H 5 NH 2 ; c) CH 3 OH; d) C 2 H 5ONa. Name the reaction products.
7. What compounds are formed at the action of the following reagents on acetamide: а) H 2 O (H + ); b) P 2 O 5 , t; c) NaNH 2 ; d) LiAlH 4 ; e) H 2 O (OH – ); f) Br 2 + KOH; g) conc. H 2 SO 4? Write the reaction equations and name the products of reactions. Point the mechanism of reactions a) and d).
8. What compounds are formed under the action of following reagents on ethyl acetate: а) H 2 O (H +); b) 2 O (OH –); c) n –С 4 Н 9 ОН; d) (СН 3) 2 NH; e) H 2O (H +); f) 2 O (OH –); g) n-C 4 H 9 OH, h) (CH 3) 2 NH? Write the schemes of reactions and name the products.
9. Write the schemes of interaction of propionitrile with the following compounds: а) H 2 O (H +); b) C 2 H 5 OH + Na; s) CH 3 MgJ, then H 2 O. Name derived substances.
10. Write the schemes of reactions that allow to make such transformations:
A. СН3–СН=СН2 ® (СН3)2СНСОNНОН;
B. HCºCH ® CH3CONHCH3;
C. CH3–CºN ® CH3OH.
11. Write structural formulas of the following compounds: 1) glyoxylic acid; 2) pyruvic acid; 3) oxaloacetic acid (ketosuccinic acid); 4) 5-oxovaleric acid; 5) 3-acetyl-2-formylhexanedioic acid; 6) methyl ester of acetoacetic acid; 7 ) hydrazone of “acetoacetic ester; 8) oxime of β–ketobutyric acid; 9) mesoxalic acid nitrile;10) diamide of oxaloacetic acid.
12. Name the following compounds:
13. Point the reaction schemes of pyruvic acid obtaining: 1) from chloroanhydride of acetate acid; 2) by the heating (pyrolysis of tartaric acid); 3) oxidation of the corresponding hydroxyacid.
14. Obtain “acetoacetic ester” from ethyl acetate. Consider the mechanism of esteric condensation by Kleisen. Write tautomeric forms of “acetoacetic ester”. Explain why a condensing reagent can be only a strong base (alcoholates of alkali metals, sodium amide or sodium hydride).
15. Write the transformations of “acetoacetic ester: 1) during the heating with diluted acid; 2) during the action of concentrated alkaline solution. Point the mechanisms of reactions.
16. Explain the CH-acidity, which grows in the following order for the next compounds: 1) acetone СН 3 -С(О)-СН 3 (К а = 3 · 10 –25 ); 2) diethylmalonate С 2 Н 5О-С(О)-СН 2 С(О)-ОС 2 Н 5 (К а = 2 · 10 –15 ); 3) “acetoacetic ester” СН 3 -С(О)-СН 2 -С(О)-ОС 2 Н 5 (К а = 7 · 10 –11 ); 4) acetylacetone СН 3 -С(О)-СН2 С(О)-СН 3 (К а = 1,5 · 10 –9). Is this sequence coincides with their propensity to enolysation? Write enol forms of these compounds. Give the definition ofketo-enol tautomery.
17. Write the reactions of “acetoacetic ester” with following substances: 1) HCN; 2) NaHSO3; 3) NH2OH; 4) CH 3C(O)Cl; 5) PCl 5 ; 6) Br 2 ; 7) Na.
18. Based on the “acetoacetic ester” and other necessary reagents propose scheme of obtaining of the following compounds: 1) methylethyl ketone; 2) 2-metylbutanoic acid; 3) isovaleric acid; 4) isobutylmethyl ketone; 5) glutaric acid; 6) heptadione-2,6.
19. What compounds will form after the interaction of pyruvic acid with such substances: 1) HCN (NaOH); 2) NaHСO 3; 3) C 6H5 -NH-NH 2 ; 4) NaHSO 3; 5) C2H5OH (H + ); 6) 150 0C, H 2 SO 4 diluted; 7) 60 …80 0C, H 2 SO 4 conc.?
20. Write the schemes of reactions of glyoxylic acid with such reagents: 1) HCN; 2) NaHІO3; 3) NH 2 OH; 4) [Ag(NH3)2]OH; 5) excess of 40% NaOH. Name theproducts.
21. What compounds are formed during the heating of these compounds: 1) β-ketocapronic acid; 2) ethylacetoacetic acid; 3) dimethylacetoacetic β-–acid; 4) β-methyl-ketovaleric .acid
22. Write the reaction equation of α-methyl and “α,α-dimethylacetoacetic ester” with following reagents: 1) H 2 SO 4 dil., t; 2) NaOH dil., t; 3) NaOH conc., t. Point the mechanisms. Indicate when will be ketone decomposition and when – acidic decomposition of β-ketoester.
23. What chemical way can be used to distinguish such pairs of compounds: 1) formylacetic acid and pyruvic acid; 2) ethyl acetate and “acetoacetic ester “; 3) sodium acetate and “sodium acetoacetic ester”?
24. Determine the structure of compound C5H8O3, which is resistant to heat, forms oximes, does not react with [Ag(NH 3 ) 2 ]OH, at the reduction of amalgamiczinc in hydrochloric acid is transformed into n-valeric acid.
25. Substance C7H12O3 forms a cherry-red solution with FeCl 3, and during the heating with diluted hydrochloric acid produces methanol, CO2 and compound C5H10O, which at the reduction by LiAlH 4 forms pentanol-2. What is the structure of compound C7H12O3.
26. In three test-tubes are acetone, pyruvic acid and acetoacetic ester. How to recognize them by chemical way?
27. Based on the acetic acid propose the schemes of obtaining of bromoacetic, hydroxyacetic and aminoacetic acids.
28. Give a definition of “alcoholic acids” and “phenoloacids”. Point scheme and mechanism of reaction of salicylic acid obtaining by the Kolbe-Schmitt method. Why acidity of salicylic acid is higher than its para-and meta-isomers? Write the schemes of qualitative reactions, which allow distinguishing of salicylic acid from: 1) phenol; 2) benzoic acid; 3) aspirin.
29. Compare the ratio to the heating of α-, β-and γ–hydroxyacids. Name the products.
30. Write the reactions that allow you to make such schemes of chemical transformations:
31. At the adding to the organic compound FeCl3, dark violet color will form. Name this compound?
A. benzoic acid
B. benzene
C. toluene
D. acetylsalicylic acid
E. salicylic acid
32. What reagent is used for the acetoacetic ester determination?
A. FeCl3
B. CuSO4
C. Formaldehyde
D. Ethyl alcohol
E. KMO4
33. Choose correct name of the following compound:
A. β–hydroxybutyric acid
B. Lactic acid
C. 3-hydroxypropionic acid
D. Glycolic acid
E. Citric acid
34. Choose correct name of the following compound:
A. β–hydroxybutyric acid
B. citric acid
C. 3-hydroxypropionic acid
D. α–hydroypropionic acid
E. glycolic acid
Correct answers of test evaluations and situational tasks:
31. E; 32. A; 33.B; 34 D.
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:
– methods of preparation, physical and chemical properties of functional derivatives of carboxylic acids;
– methods of preparation, physical and chemical properties of the major heterofunctional carboxylic acids.
Student should be able to:
– to recognize functional and heterofunctional derivatives of carboxylic acid by the usage of qualitative reactions;
– to identify them with the usage of physical methods of analysis;
– to carry out reactions that characterized the most important functional chemical properties of carboxylic acids.
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_14.Heterofunctional carboxylic acids.
9. http://intranet.tdmu.edu.ua/data/kafedra/internal/zag_him/presentations/pharmaceutical/pharmacy/full_time_study/organic_chemistry/2_course/lecture_09.Heterofunctional carboxylic acids.
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
