MED-108 Organic Chemistry Carboxylic Acids PDF

MED-108 Organic Chemistry Carboxylic Acids Structure and Properties Methods of Preparation – Chemical Reactions LOBs covered Discuss the physical properties of carboxylic acids Discuss the effect of chemical structure on the degree of acidity of carboxylic acids Describe methods of preparation of ca...

MED-108 Organic Chemistry Carboxylic Acids Structure and Properties Methods of Preparation – Chemical Reactions LOBs covered Discuss the physical properties of carboxylic acids Discuss the effect of chemical structure on the degree of acidity of carboxylic acids Describe methods of preparation of carboxylic acids Identify reagents and products in reactions of carboxylic acids PART A Physical and Chemical Properties Carboxylic Acids Small carboxylic acids exist in the liquid phase The formation of acid dimers involves strong hydrogen bonds and this makes even small carboxylic acids liquids Boiling Points Alcohols and carboxylic acids both form hydrogen bonds However: Carboxylic acids form twice as many hydrogen bonds than alcohols Carboxylic acids also have an extra oxygen atom (LDF) Carboxylic Acids Carboxylic acids are weakly acidic Donate protons React with common bases Carboxylate Anion The dissociation of a carboxylic acid produces a carboxylate anion Carboxylic acids are weak acids Weak Acid Dissociation The lower the Ka value, the weaker the acid. The higher the pKa value, the weaker the acid Weak Acid Dissociation Weak Acid Dissociation Carboxylic acid strength is affected greatly by the stability of the conjugate base A stable conjugate base drives the equilibrium to the right, producing more H+ ions, making the acid stronger Conjugate Base Stability The carboxylate anion is stabilized by resonance Carboxylic Acid Acidity HCOOH pKa = 3.75 CH3COOH pKa = 4.74 Why is formic acid stronger than acetic acid? Carboxylic Acid Acidity HCOOH pKa = 3.75 CH3COOH pKa = 4.74 Why is formic acid stronger than acetic acid? A methyl group is electron-donating Further Explanations for Revision HCOOH pKa = 3.75 CH3COOH pKa = 4.74 Why is formic acid stronger than acetic acid? The methyl group (-CH3) is electron-donating. It gives negative charge to the conjugate base O atoms in the resonance hybrid. Increasing the negative charge in the conjugate base makes it less stable. If the conjugate base is less stable, the equilibrium shifts to the left, giving less dissociation, and of course lower amounts of H3O+. Thus, acetic acid is weaker than formic acid. Carboxylic Acid Acidity CH3COOH pKa = 4.74 ClCH2COOH pKa = 2.85 Why is 2-chloroacetic acid stronger than acetic acid? Chlorine atom draws electron charge away – stabilizes conjugate base Further Explanations for Revision CH3COOH pKa = 4.74 ClCH2COOH pKa = 2.85 Why is 2-chloroacetic acid stronger than acetic acid? Looking at the conjugate base, the Cl atom, which is highly electronegative, draws electron density towards it. This means that the negative charge on the O atoms in the resonance hybrid will be reduced. Reducing the negative charge on the conjugate base, increases its stability. If the conjugate base is made more stable, the equilibrium will shift to the right, giving more dissociation products, increasing the amount of H3O+, and the acidity of the 2-chloroacetic acid. Another way to see this issue is to consider the original acid on the left side. The electronegative Cl will draw electron density from the rest of the molecule. This weakens the O-H bond, leading to more dissociation, and a stronger acid. 5-Minute Break An Alternative Explanation CH3COOH pKa = 4.74 ClCH2COOH pKa = 2.85 Concentrate on the strength of the O–H bond Further Explanations for Revision CH3COOH pKa = 4.74 ClCH2COOH pKa = 2.85 Concentrate on the strength of the O–H bond A methyl group (-CH3) is electron-donating. Electron density flows towards the carboxylic acid group, and this makes the O-H bond thicker and stronger. Thus, in acetic acid, it is more difficult to break the O-H bond to produce H+ ions. This makes acetic acid weaker. A chlorine atom is highly electronegative. This draws electron density away from the carboxylic acid group, and this makes the O-H bond thinner and weaker. This, in chloroacetic acid, it is easier to break the O-H bond to produce H+ ions. This makes chloroacetic acid stronger. Structure and Acidity Look at the left column. Compounds XCH2CO2H involve a halogen atom. As the electronegativity of the X atom increases, so does the strength of the acid. Look at the right column. The second, third, and fourth compounds from the top involve a Cl atom. As the Cl atom gets closer to the COOH group, the electron withdrawing effect of the Cl atom increases, making the acid stronger. Acidity and Boiling Point Is there a correlation between acid strength and boiling point? Acid pKa Boiling point (C) FCH2COOH 2.65 165 F2CHCOOH 1.34 136 CF3COOH 0.00 72 Clearly, the stronger the acid, the lower the boiling point Acidity and Boiling Point WHY is there a inverse correlation between the acid strength and the boiling point? An electron-withdrawing R group takes electron density away from the hydrogen bonds, weakening them and making it easier for the acid to boil An electron-withdrawing R group takes electron density away from the O-H bond of the acid molecule, making it easier for the proton to dissociate Summary for Revision Carboxylic acids form dimers through hydrogen bonding. This makes even small carboxylic acids liquids. Carboxylic acids are fairly weak acids. The have low Ka values and high pKa values, relative to mineral acids such as HCl. The reason carboxylic acids are acidic at all is that the carboxylate anion (conjugate base) formed on dissociation is stabilized through resonance. Two resonance forms ensure that the negative charge is spread over both O atoms, increasing the stability of the conjugate base and leading to more dissociation. The presence of electron-donating groups (e.g. alkyl groups) on the conjugate base, increase the negative charge and destabilize the base, leading to lower dissociation, and a weaker acid. The presence of electron-withdrawing atoms on the conjugate base, decrease the negative charge, stabilize the base, and increase the degree of dissociation , making the acid stronger. An alternative explanation involves examining the O-H bond strength. The presence of an electron-donating group next to the –COOH group gives electron density to the O-H bond, making it stronger and more difficult to break. This reduces the acidity. The presence of a highly electronegative atom close to the –COOH group, draws electron density away, making the O-H bond weaker, and easier to break. This increases acidity. As the degree of acidity increases, the boiling point decreases, and vice versa. This can be explained by considering the effect of groups connected to the -COOH group. Electron-withdrawing groups will weaken both the hydrogen bonds in the dimers, as well as the O-H bonds, leading to lower boiling point and higher degrees of acidity. PART B Methods of Preparation Methods of Preparation Previously covered methods - oxidative cleavage of alkenes (KMnO4) - oxidative cleavage of alkynes (KMnO4 or O3) - oxidation of 1o alcohols or aldehydes - hydrolysis of nitriles New method - carboxylation of Grignard reagents Alkene Oxidative Cleavage Addition of KMnO4 solution to an alkene causes the alkene to split-up and the two pieces to become fully oxidized KMnO4 solution is purple – if it reacts with alkene, it is decolorized If the alkene is terminal, CO2 gas will be formed Oxidative Cleavage of Alkynes KMnO4 in acid or base, or O3 (ozone) Products – carboxylic acids Oxidative Cleavage of Alkynes If terminal alkyne – CO2 formed as well This is a diagnostic for the position of the triple bond Oxidation of Alcohols Alcohols are oxidized to carbonyl compounds Oxidizing agents KMnO4 CrO3 Na2Cr2O7 Alcohol Oxidation Primary alcohol → aldehyde → carboxylic acid (usually cannot halt the oxidation) Oxidation of aldehydes Oxidizing agents are usually KMnO4 in hot HNO3 or CrO3 in strongly acidic conditions The problem with these oxidizing agents is that they work under highly acidic conditions and this may damage a sensitive part of the molecule Oxidation can also be carried out in alkaline conditions by using Ag2O in aqueous ammonia solution (NH4OH(aq)) (Tollens’ test - silver mirror test) Oxidation of aldehydes Hydrolysis of Nitriles Mildly acidic or alkaline solution with application of heat Carboxylation of Grignard Reagents (NEW) Add dry ice (CO2(s)) to a Grignard reagent 5-Minute Break PART C Reactions of Carboxylic Acids Reactions of Carboxylic Acids (a) (b) (c) (d) (e) Production of an acid chloride Production of an acid anhydride Production of an ester Production of an amide Deprotonation (acid + base reaction) Nucleophilic Acyl Substitution This is the general type of reaction that carboxylic acids undergo with a variety of compounds Nu – nucleophile X – leaving group This reaction takes place because the carbonyl group C is δ+ Nucleophilic Acyl Substitution Aldehydes and ketones do not have good leaving groups …therefore they do not undergo acyl substitution reactions (we have seen that they undergo nucleophilic addition reactions) Nucleophilic Acyl Substitution Carboxylic acids have –OH as the leaving group. It is not a good leaving group, but treatment with acid (protonation) makes it a good leaving group (a) Production of an acid halide (b) Production of an acid anhydride Reaction takes place at 800 oC. High temperature can destroy larger more sensitive acids, hence only good for acetic anhydride (c) Production of an Ester Fischer esterification reaction Carboxylic acid + Alcohol → Ester + Water (d) Production of an amide Carboxylic acid + amine → amide + water (e) Reaction with base Carboxylic acid + base → carboxylate + water Hydrolysis of carboxylic acid derivatives Carboxylic acid derivatives have been seen to form through condensation (dehydration) reactions. Hence, when you add water to them, they react to form the original carboxylic acid Summary for Revision Carboxylic acids form by a variety of methods: oxidative cleavage of appropriate alkenes, oxidative cleavage of alkynes, oxidation of primary alcohols, hydrolysis of carboxylic acids derivatives (e.g. nitriles, esters), and by carboxylation of Grignard reagents. Typical reactions of carboxylic acids follow a nucleophilic acyl substitution mechanism. This is where a nucleophile attacks the carbonyl group C atom, connecting onto it, and this continues with the disposal of a leaving group. Reactions of carboxylic acids include formation of acid chlorides, production of acid anhydrides (limited to acetic anhydride), formation of an ester by reaction with an alcohol, production of an amide through reaction with an amine, and reaction with a base, a typical acid-base reaction, forming an organic salt and water. All carboxylic acid derivatives can be hydrolyzed under mildly acidic or alkaline conditions to form the original carboxylic acids.