FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 1 / 6 Analizată și aprobată la ședința catedrei din, proces verbal nr șeful catedrei de Biochimie și Biochimie Clinică, conferențiar universitar, doctor habilitat în științe medicale Olga Tagadiuc Methodical indication N.4 Theme: Reactivity of organic compounds (alcohols, thiols, amines, aldehydes, carboxylic acids). Types of organic reactions. Stereoisomerism. 1. Bromination of unsaturated organic compounds. The background. Bromination reaction of alkenes occurs easy in normal conditions as electrophilic addition mechanism (AN). In bromine molecule the bond cleavage down heterolytically (Br : Br Br + + Br ). The bromide cation Br + that is formed attacks the alkene molecule (oleic acid) at π-bond. As a result a carbocation is formed that reacts with bromide anion Br. Procedure. Add to a test tube 3 4 drops of oleic acid solution (СН3 (СН2)7 СН=СН (СН2)7 СООН) and dissolve it in tetrachloromethane CCl4. To the obtained solution add 4 5 drops of 5% bromine in tetrachloromethane. Note the observed changes. Bromination reaction represent a qualitative reaction for unsaturated compounds. Write the bromination reaction of of oleic acid. Explain the spatial direction of reaction and name the obtained product.
FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 2 / 6 2. The obtaining of tribromoaniline. The background. The reaction is characteristic for aromatic molecules and occur according a electrophilic substitution reaction with the formation of π- and σ- complexes (SE reaction). Procedure. Introduce in a test-tube a drop of aniline and 5 6 drops of water and shake it well. Add some drops of bromine water till the white precipitate of 2,4,6-tribromoaniline is formed. The reaction occurs quantitatively and is used to identify aniline and its derivatives. Write the scheme of aniline bromination. Explain the influence of amino group in this 3. The obtaining of chloroethane from ethanol. The background. The substitution of OH group with Cl occurs according to nucleophilic substitution reaction (SN1). The substitution of hydroxyl anion is possible only if the leaving anion is more stable than the one which replace. Hydroxyl anion is less stable then chloride anion that is why the reaction must run in acid solution. Procedure. To a dry test tube add two scapula of sodium chloride. Add 5 6 drops of ethanol, 3 4 drops of concentrated sulphuric acid and heat the solution but do not allow the abundant elimination of hydrogen chloride. Time after time approach the opening of the test-tube to the flame. The eliminated gas burns with a green flame. Write the scheme of chloroethane obtaining. What is the mechanism of this reaction? What role has sulfuric acid in this reaction?
FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 3 / 6 4. Dehydration of ethanol. The background. The characteristic reactions for alcohols are not only the substitution reactions (SN) but also the elimination reactions (E reactions). Because hydroxyl group is a bad leaving group it needs to be protonated first to create a good leaving group. Dehydration of alcohols occurs in a strong acid solution. Three steps can be identified in dehydration reaction: I-st step represent the protonation of alcohol by a strong acid; 2-nd dissociation of the oxonium ion and formation of a carbocation; 3-rd removing of proton by a base (water). Dehydration of alcohol undergo monomolecular elimination mechanism (E1). Procedure. In a test tube place 8 drops of concentrated sulfuric acid, 4 drops of ethanol and a half spatula of aluminum oxide. Fix the test tube in a holder, close it with a rubber stopper with a delivery tube and introduce the end of the delivery tube in a solution with bromine water. Warm the reactive solution and as soon the color of bromine solution disappear, quickly introduce the delivery tube in a test tube with 2% solution of potassium permanganate. Continue to warm the reactive test tube and observe what is happening with the permanganate solution. Write the scheme of ethanol dehydration. What is the mechanism of this reaction? What product is formed in ethanol dehydration reaction?
FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 4 / 6 5. The obtaining of ethyl acetate. The background. Esters can be obtained in different ways. One method is the esterification reaction that represent the acylation of alcohol molecule with carboxylic acid. The reaction occurs according to nucleophilic substitution mechanism (SN - reaction). Reaction of esterification all the time is realized in the presence of a strong acid (sulphuric acid) that plays the role of the catalyst. Proton (the catalyst) H + reacts with the lone pair of electrons of oxygen atom from carbonyl group. The protonated acid react with the molecule of alcohol (nucleophile reagent) with the formation of oxo cation I that transform to oxo cation II that eliminate one proton. As a result ethyl acetate is created. Procedure. Introduce in a dry test-tube 2 3 spatulas of sodium acetate (anhydride), 3-4 drops of ethanol and 3 4 drops of concentrated sulphuric acid. Heat attentively the mixture until it begin to boil. The eliminated gas have a characteristic smell of ethyl acetate. The reaction is used for ethanol identification. Write the reaction and describe its mechanism. What is the mechanism of this reaction? What is the role of sulphuric acid in reactions of esterification?
FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 5 / 6 1. sp 3 - and sp 2 hybridization of carbon atom. 2. Electronegativity of elements. 3. Polarity and polarization of bonds. 4. Electronic effects of substituents. 5. Types of reagents. Initial level. Self-Assessment Questions. 1. Classification of organic chemical reactions. 2. Types of reagents. Examples. 3. Chemoselective, regioselective, stereoselective reactions. 4. Condensation reactions and their biological importance. 5. Stereoisomerism of organic compounds. Case study. 1. Sorbic acid CH3 CH=CH CH=CH COOH is an effective antiseptic. Show the distribution of electronic density in the diene system influenced by the substituents in comparison with butadien-1,3. 2. At one step of three carbonic acids cycle fumaric acid (butanedioic acid) is transformed in malic acid (2-hydroxybutanedioic acid). Write this reaction in vivo and explain the mechanism. 3. Nervous disorders are observed when exposed to large doses of hydrazine and its derivatives (isoniazid). Describe the action mechanism of hydrazine if it reacts with pyridoxal phosphate. Self-Control Test. 1. What reagents from below mentioned are nucleophiles? А. CH3, B. OH, C. NO2, D. NH2, E. CH3. 2. What reagents from below mentioned are electrophiles? А. H2O, B. H +, C. AlCl3, D. SO3H, E. NH3. 3. What class of organic compounds represent the product of glutaric acid dehydration? A. hydrocarbons, B. aldehydes, C. anhydrides, D. carboxylic acids, E. ketones. 4. What type of reactions represent acylation reactions? A. SN, B. AE, C. AN, D. SE, E. E. 5. The mechanism type of alcohol etherification with carboxylic acids is: A. AN, B. SE, C. SN, D. E1, E. AE.
FACULTATEA SĂNĂTATE PUBLICĂ, ANUL I Pag. 6 / 6 6. What acid forms during heating acetic acid and carbon dioxide? A. oxalic, B. malonic, C. succinic, D. glutaric, E. adipic. 7. Which derivative of carboxylic acids is the most reactive in nucleophilic substitution reactions? A. anhydrides, B. chloro anhydrides, C. carboxylic acids, D. esters, E. amides. 8. What kind of reaction is the interaction of butadien-1,3 with HBr? A. nucleophilic addition, B. electrophilic substitution, C. electrophilic addition, D. nucleophilic substitution, E. elimination. 9. What reaction type characterize the formation of isocitric acid from cis-aconitic acid? A. dehydration, B. acylation, C. hydration, D. elimination, E. oxidation. 10. Which acid is named valerianic? А. C2H5COOH, B. C3H7COOH, C. C4H9COOH, D. C5H11COOH, E. C6H5COOH.