SCH 206 Carboxylic acids General structure Carboxyl group O H R O Acidic
R= alkyl, alkenyl, alkynyl or aryl The word carboxy (for a COOH group) is derived from carbonyl (C=O) + hydroxy (OH).
Dr. Solomon Derese 17 SCH 206 Structure and Physical Properties of Carboxylic Acids
O Carbonyl H R O Hydroxyl
Structurally related to both carbonyl (aldehydes/ketones) and alcohol functional groups. As a result their properties are related to these functional groups. Dr. Solomon Derese 18 SCH 206 The properties of carboxylic acids depends on the carbonyl and the hydroxyl group and their interaction.
d Basic site
d Nucleophiles attack here
Dr. Solomon Derese 19 SCH 206 The –OH group is electron donating there by making the carbonyl carbon less electrophilic compared to the carbonyl group of aldehydes and ketones, therefore, less reactive.
The carboxyl group is stabilized by resonance relative to the carbonyl group in aldehydes and ketones, and is therefore, less reactive. For these reasons, many reagents that react with the carbonyl group of aldehydes and ketones react more slowly or only in the presence of catalysts when attacking the carbonyl group of carboxylic acid. Dr. Solomon Derese 20 SCH 206 Carboxylic acids are similar in some respects to both aldehydes/ketones and alcohols. Just like alcohols, carboxylic acids are strongly associated due to hydrogen bonding. d+ d- + d- - d + d d High boiling
Hydrogen bonding in alcohols The melting and boiling points of carboxylic acids are among the highest known for comparable weight because of extremely strong hydrogen bonding.
Dr. Solomon Derese 21 SCH 206 This is because a pair of carboxylic acid molecules are held together not by one but by two hydrogen bonds and as a result exist as cyclic dimers. - d- d+ d
H-bonding
+ - d d d- Carboxylic acid dimer In the liquid state a mixture of hydrogen bonded dimers as well as higher aggregates is present.
Dr. Solomon Derese 22 Examples SCH 206 O H H C O Propyl alcohol 3 Acetic acid M. Wt = 60 M. Wt = 60 b.p. = 97°C b.p. = 118ºC In aqueous solution hydrogen bonding between carboxylic acids is replaced by H-bonding between carboxylic acid and water. As a result of this carboxylic acids of four or fewer carbon atoms are miscible in water in all proportions.
Dr. Solomon Derese 23 Acidity of carboxylic acids SCH 206 As their name implies carboxylic acids are acidic. They are the most acidic among compounds that contain only carbon, hydrogen and oxygen. Dissociation/Ionization of an acid
Hydrochloric acid (HCl) undergoes 100% ionization. Carboxylic acids are weak acids, for example a 0.1 M solution of acetic acid in water, is only 1.3 % ionized. Dr. Solomon Derese 24 SCH 206 Bronsted – Lowry’s definition: An acid is a proton donor
[RCO2 ][H3O ] Keq [RCO2H][H2O] For a dilute aqueous solution, the concentration of water is essentially constant (≈55M)
Dr. Solomon Derese 25 SCH 206 [RCO2 ][H3O ] Ka Keq[H2O] [RCO2H] Acidity constant (a measure of the strength of an acid) Acid strength is defined as the tendency to give up a proton.
The higher the value of Ka, the stronger the acid.
pKa logKa
The larger the value of pKa, the weaker the acid.
Acetic acid for example has a pKa of 4.8. Although much weaker than mineral acids, carboxylic acids are nevertheless much stronger acids than alcohols. The pKa of ethanol is for example 16. Dr. Solomon Derese 26 What determines the strength of acids? SCH 206
Acid Base Conjugate base Conjugate acid Examples
pKa = 4.75
pKa = 16
Dr. Solomon Derese 27 Factors affecting the strength of an acid SCH 206 I. The electronegativity of A in H-A The more polarized the bond the weaker the bond and stronger the acid. Examples pKa = 50 34 d- d+ 10 times < pKa = 16 more acidic!!! Weak/polar bond In a covalent single bond between unlike atoms the electron pair forming the d bond is never shared equally between the two atoms, it tends to be attracted more towards the more electron negative atom of the two. This is called the inductive effect. Dr. Solomon Derese 28 SCH 206 In both ethanol and acetic acid, the O-H bond is polarized by the greater electronegativity of the oxygen atom. + + d- < d+ d the CH2 group in the corresponding position of ethanol. Dr. Solomon Derese 29 II. Stability of A:- relative to A-H SCH 206 A. Inductive Effect The electron attracting inductive effect of the carbonyl carbon stabilizes the acetate ion by attracting electrons away from the oxygen thereby stabilizing the acetate. d+ In the case of the ethoxide the negative charge is localized on the oxygen making it very unstable. Dr. Solomon Derese 30 b) Resonance effect SCH 206 Resonance leads to stability. Generally speaking, the larger the number of resonance forms, the more stable a substance is because electrons are spread out over a larger part of the molecule and are closer to more nuclei. Resonance effect also contribute to the increase acidity of acetic acid relative to ethanol. No resonance No resonance stabilization stabilization An alcohol dissociates to give an alkoxide ion, in which the negative charge is localized on a single electronegative atom. Dr. Solomon Derese 31 SCH 206 O O H C 3 H3C O H O The two resonance The two resonance structures are not equivalent structures are equivalent and the lower structure and no charge separation requires charge separation, and therefore unstable. Large resonance stabilization Small resonance stabilization This differential stabilization drives the equilibrium forward. Dr. Solomon Derese 32 SCH 206 There is effective delocalization, with consequent stabilization, in the acetate (carboxylate) anion as it has two resonance forms of equal energy, and though delocalization can take place in the acetic acid molecule, this involves separation of charges and will consequently be much less effective as a stabilizing influence because the resonance forms are not equal in energy. The effect of this differential stabilization somewhat discourage the recombination of proton with the carboxylate anion, the equilibrium as a result is displaced to the right, and therefore acetic acid is, by organic acids standard a moderately strong acid. Dr. Solomon Derese 33 SCH 206 Substituent Effects on Acidity of Carboxylic Acids Undissociated carboxylic acid Carboxylate anion Any factor that stabilizes the carboxylate anion relative to the undissociated carboxylic acid will drive the equilibrium forward and results in increased acidity. Conversely, any factor that destabilizes the carboxylate relative to the undissociated acid will result in decrease acidity. An electron withdrawing group (EWG) attached to the carboxyl inductively withdraw electron density, thereby, stabilizing the carboxylate anion and increasing acidity. Dr. Solomon Derese 34 SCH 206 EWG reduces the negative charge on the carboxylate ion making it less reactive/stable. Any effect that result in electron-withdrawal from a negatively charged center is stabilizing effect because it spreads the charge and consequently decrease the electron density. pKa = 4.75 2.85 1.48 0.64 Acidity Dr. Solomon Derese 35 SCH 206 pK = 1.68 pKa = 2.85 a The nitro group is a stronger EWG than Cl. The more electronegative the substituent, the stronger the acid. pKa = 2.8 2.6 F is more electronegative than Cl. Dr. Solomon Derese 36 SCH 206 Since inductive effects operate through d bonds and are dependent on distance, the effect of substituent decrease as the substituent is moved further from the carboxyl. pKa = 4.52 4.1 2.86 The closer the electron-withdrawing group to COOH, the stronger the acid. Dr. Solomon Derese 37 SCH 206 EDG increases the negative charge on the carboxylate ion making it more reactive (unstable). An electron-donating group (EDG) should have exactly the opposite effect, destabilizing the carboxylate anion and decreasing acidity. pKa = 5.05 4.86 4.88 4.75 3.75 An alkyl group is a weak Electron Donating Group. Dr. Solomon Derese 38 SCH 206 The hybridization of the group that is directly attached to the carboxyl group affect its acidity. pKa = 4.75 4.3 4.2 1.8 This is because, the carbon becomes more electronegative (EWG) as its “S” character increase. Dr. Solomon Derese 39 SCH 206 Benzoic acid is a stronger acid than acetic acid. The acidity of substituted benzoic pKa acid derivatives Substituent (Y) Ortho Meta Para depends on the EW H 4.2 4.2 4.2 nature of the CH3 3.9 4.3 4.4 substituent and the F 3.3 3.9 4.1 position of Cl 2.9 3.8 4.0 attachment. CH3O 4.1 4.1 4.5 NO2 2.2 3.5 3.4 Dr. Solomon Derese 40 SCH 206 pKa = 2.2 3.5 3.4 Strong Inductive effect Medium Inductive effect Weak Inductive effect Resonance effect No resonance effect Resonance effect Resonance contribution having a positive charge at the carbon atom bearing the carboxylate anion can be written for the ortho and para isomers of nitrobenzoic acid, whereas the nitro group in the meta position exerts primarily an inductive effect. Dr. Solomon Derese 41 SCH 206 This resonance contributor puts a positive charge on the carbon atom to which the carboxylate ion is bound Dr. Solomon Derese 42 Assignment 19 SCH 206 I. Arrange the compounds in each of the following sets in increasing order of acidities. Give reasons for your answers. a) 3-Chloropentanoic acid; 2-Chloropentanoic acid; 4- Chloropentanoic acid; pentanoic acid; 5-Chloropentanoic acid b) Propanoic acid; 2-Methylpropanoic acid; 2,2- Dimethylpropanoic acid c) 2-Methoxybutanoic acid; 3-Chlorobutanoic acid; 4- Iodobutanoic acid d) Benzoic acid; p-Nitrobenzoic acid; p-Methoxybenzoic acid e) p-Nitrobenzoic acid; Acetic acid; Benzoic acid Dr. Solomon Derese 43 SCH 206 II. Some pKa data for simple dibasic acids are shown. How can you account for the fact that the difference between the first and second ionization constants decreases with increasing distance between the carboxyl groups. Name Structure pKa1 pKa2 Oxalic acid HO2CCO2H 1.2 4.2 Succinic acid HO2C(CH2)2CO2H 4.2 5.6 Adipic acid HO2C(CH2)4CO2H 4.4 5.4 III. The following pKa values have been measured. Explain why a hydroxyl group in the para position decreases the acidity while a hydroxyl group in the meta position increases the acidity. Dr. Solomon Derese 44 SCH 206 IV. Arrange the following compounds in increasing order of acidity. Explain. Dr. Solomon Derese 45 Preparation of carboxylic acids SCH 206 Oxidation Oxidation of alkylbenzenes [O] O R O H R = Alkyl Most commonly used oxidizing agent are hot: or Example KMnO4 (HOT) O CH3 H2O, HEAT O H This show how the aromatic ring is stable. The benzene ring is inert to the oxidizing agents. Dr. Solomon Derese 46 SCH 206 The mechanism of side chain oxidation is complex and involves the attack on C-H bonds at the position next to the aromatic ring to form benzylic radical intermediates. No reaction Dr. Solomon Derese 47 Oxidative cleavage of alkenes SCH 206 or KMnO4/NaCr2O7/K2CO3 i. O3 - H O , NaOH, H O ii. Ag2O, OH or 2 2 3 Oxidation of primary alcohols - + O H i. KMnO4, :OH, Heat ii. H3O R RCH OH 2 OR O 0 1 CrO3, H2O, H2SO4 (Jones reagent) Dr. Solomon Derese 48 Hydrolysis of nitrites SCH 206 This method works with primary Na C N SN2 halides, since competitive E2 elimination can occur when secondary R X and tertiary halides are used. Alkyl halide Methyl, primary alkyl halide Dr. Solomon Derese 49 Examples SCH 206 Dr. Solomon Derese 50 Hydrolysis of cyanohydrins SCH 206 Dr. Solomon Derese 51 Mechanism of acid hydrolysis of nitriles SCH 206 H H O H H C N R C N H R OH H OH H O H C N H R OH H Dr. Solomon Derese 52 Carboxylation of Grignard reagent SCH 206 O C O In order to use the Grignard method, the alkyl halide used to prepare the Grignard MUST NOT contain any exposed functional groups that react with a Grignard reagent or inhibit its formation, i. e., OH, NH, SH, C=O, S=O, N=O, C≡CH, C≡N, epoxide. Dr. Solomon Derese 53 SCH 206 Dr. Solomon Derese 54 Assignment 20 SCH 206 I. Write the mechanism for basic hydrolysis of nitrile. II. Which method - Grignard carboxylation or nitrile hydrolysis would you use for each of the following reactions? Explain your choice. Dr. Solomon Derese 55 SCH 206 III. Identify the missing reagents a – f in the following scheme: Dr. Solomon Derese 56