Carboxylic Acid and Derivatives Notes PDF

Carboxylic acid and Derivatives Learning outcomes: Define and classify carboxylic acids Be familiar with the common names and IUPAC system of naming carboxylic acids Explain the reactivity and physical properties of carboxylic acids, including the effects of substituents on their acidity...

Carboxylic acid and Derivatives Learning outcomes: Define and classify carboxylic acids Be familiar with the common names and IUPAC system of naming carboxylic acids Explain the reactivity and physical properties of carboxylic acids, including the effects of substituents on their acidity Discuss the reactions of carboxylic acids and illustrate their general mechanism of reaction. List and briefly explain the various ways carboxylic acids and their derivatives are synthesized. Qualitative tests for carboxylic acids Carboxylic acid and Derivatives Carboxylic acids are organic compounds containing one or more carboxyl groups. The Carboxyl group which is usually written in the condensed structure as —COOH, consists of a C═O with —OH bonded to the same carbon.  Classes of Carboxylic acids 1). Classification based on group attached to the carboxyl group: A. Aliphatic carboxylic acid: When hydrogen (H) or Alkyl group (R) is attached to the carboxyl group (H is attached) (R is attached)  Classification Continued B.Aromatic carboxylic acids: When an Aryl group (Ar) is attached 2).Based on the number of Carboxyl groups: Mono-,di-, tri- and Polycarboxylic acids Acetic acid Citric acid  Naming Carboxylic acids Simple open-chain carboxylic acids are named by replacing The terminal -e of the corresponding alkane name with - oic acid. The -CO2H carbon is numbered C1.  Compounds that have a - CO2H group (a carboxyl group) bonded to a ring, are named using the suffix - carboxylic acid. The carboxyl carbon is attached to C1 on the ring and is not itself numbered.  Aromatic Acids Aromatic acids are named as derivatives of benzoic acid. Ortho-, meta- and para- prefixes are used to specify the location of a second substituent. Numbers are used to specify locations when more than 2 substituents areChapter present. 20 8  Naming complicated carboxylic acids For molecules with two carboxylic acid groups, the carbon chain in between the two carboxyl groups (including the carboxyl carbons) is used as Ethanedioic acid (Oxalic acid) the longest chain; the suffix -dioic acid is then added. For molecules with more than two carboxylic acid groups, the carboxyl groups are named as substituents. Common names of some Di & Tricarboxylic acids Citric acid Aconitic acid (2-hydroxypropane -1,2,3-tricarboxylic acid) (Propene-1,2,3-tricarboxylic acid) 2-Hydroxybutanedioic Fumaric acid acid (2-Butenedioic (Malic acid) acid)  Resonance Structures of Formic Acid Carbon is sp2 hybridized. Bond angles are close to 120. O—H eclipsed with C═O, to get overlap of  orbital with orbital of lone pair on oxygen. Chapter 20 12  Boiling Points Like alcohols, carboxylic acids form strong intermolecular hydrogen bonds. Most carboxylic acids, in fact, exist as dimers held together by two hydrogen bonds. This strong hydrogen bonding has a noticeable effect on boiling points, making carboxylic acids boil at substantially higher temperatures than alkanes or alcohols of similar molecular weight. Acetic acid, for instance has a boiling point of 117.9 °C, versus 78.3 °C for ethanol.  Melting Points Aliphatic acids with more than 8 carbons are solids at room temperature. Double bonds (especially cis) lower the melting point. The following acids all have 18 carbons: Stearic acid (saturated): 72C Oleic acid (one cis double bond): 16C Linoleic acid (two cis double bonds): -5C The melting pts of dicarboxylic acids are relatively high, due to two carboxyl groups per molecule. Chapter 20 14  Solubility Water solubility decreases with the length of the carbon chain. With up to 4 carbons, acid is miscible in water. Very soluble in alcohols. Also soluble in relatively nonpolar solvents like chloroform because the hydrogen bonds of the dimer are not disrupted by the nonpolar solvent. Chapter 20 15  Acidity of carboxylic acids A carboxylic acid may dissociate in water to give a proton and a carboxylate ion. The equilibrium constant Ka for this reaction is called acid-dissociation constant. Although much weaker than mineral acids, carboxylic acids are nevertheless much stronger acids than alcohols and phenols. The Ka of ethanol, for example, is approximately 10 -16, making ethanol a weaker acid than acetic acid by a factor of 10 11 The dissociation of either an acid or alcohol involves breaking O-H bond. However, that of carboxylic acid gives a carboxylate ion with the negative charge spread out equally over two oxygen atoms.  Why are carboxylic acids so much more acidic than alcohols? Why are carboxylic acids so much more acidic than alcohols even though both contain -OH groups? To answer this question, compare the relative stabilities of carboxylate anions versus alkoxide anions. In an alkoxide ion, the negative charge is localized on one oxygen atom, but in a carboxylate ion, the negative charge is spread out over both oxygen atoms, This is because a carboxylate anion is a resonance hybrid of two equivalent structures. Because a carboxylate ion is more stable than an alkoxide ion, it is lower in energy and is present to a greater extent at equilibrium. A carboxylate ion  Substituent Effects on Acidity The magnitude of a substituent effect depends on its distance from the carboxyl Chapter 20 group. 18  Aromatic Carboxylic Acids Electron-withdrawing groups enhance the acid strength and electron-donating groups decrease the acid strength. Effects are strongest for substituents in the ortho and para positions. Chapter 20 19  Synthesis Review Oxidation of primary alcohols and aldehydes with chromic acid. Alkyl benzene oxidized to benzoic acid by hot KMnO 4 or hot chromic acid Cleavage of an alkene with hot KMnO 4 (Oxidation)produces a carboxylic acid if there is a hydrogen on the double- bonded carbon. Carboxylation of Grignard reagents Hydrolysis of Nitriles Chapter 20 20 Oxidation of Primary Alcohol to Carboxylic Acids Primary alcohols and aldehydes are commonly oxidized to acids by chromic acid (H2CrO4 formed from Na2Cr2O7 and H2SO4). Potassium permanganate is occasionally used, but the yields are often lower. Chapter 20 21  Cleavage of Alkenes Using KMnO4 Warm, concentrated permanganate solutions oxidize the glycols, cleaving the central C═C bond. Depending on the substitution of the original double bond, ketones or acids may result. Chapter 20 22  Alkyne Cleavage Using Ozone or KMnO4 With alkynes, either ozonolysis or a vigorous permanganate oxidation cleaves the triple bond to give carboxylic acids. Chapter 20 23 Side Chain Oxidation of Alkylbenzenes Chapter 20 24  Conversion of Grignards to Carboxylic Acids Grignard reagent react with CO2 to produce, after protonation, a carboxylic acid. This reaction is sometimes called “CO2 insertion” and it increases the number of carbons in the Chapter 20 25 molecule by one. Formation and Hydrolysis of Nitriles CH2Br CH2CN + CH2CO2H NaCN H , H2O acetone Phenylacetic acid Benzyl bromide Basic or acidic hydrolysis of a nitrile (—CN) produces a carboxylic acid. The overall reaction, starting from the alkyl halide, adds an extra carbon to the molecule. Chapter 20 26  Hydrolysis of Fats and Oils Fatty acids which are long chain carboxylic acids, are obtained from the hydrolysis of fats and oils. The basic hydrolysis of fat and oils produces soap (this reaction is known as saponification). Chapter 20  Acid Derivatives The group bonded to the acyl carbon determines the class of compound: —OH, carboxylic acid —Cl, acid chloride —OR’, ester —NH2, amide These interconvert via nucleophilic acyl substitution. Chapter 20 28  Nucleophilic Acyl Substitution Carboxylic acids react by nucleophilic acyl substitution, where one nucleophile replaces another on the acyl (C═O) carbon atom. Chapter 20 29  Nucleophilic addition reaction Vs Nucleophilic Acyl substitution reaction Both reactions begin with the addition of a nucleophile to a polar C=O bond to give a tetrahedral, alkoxide ion intermediate. The intermediate formed from an aldehyde or ketone is protonated to give an alcohol, but the intermediate formed from a carboxylic acid derivative expels a leaving group to give a new carbonyl compound.  Carboxylic Acids and Their Reactions The direct nucleophilic acyl substitution of a carboxylic acid is difficult because -OH is a poor leaving group. Thus, it’s usually necessary to enhance the reactivity of the acid, either by using a strong acid catalyst to protonate the carboxyl and make it a better acceptor or by converting the -OH into a better leaving group  Conversion of an Acid into Alcohol (RCO2H RCH2OH) Carboxylic acids are reduced by lithium aluminum hydride (LiAlH4) to yield primary alcohols. The reaction occurs by initial substitution of the acid -OH group by -H to give an aldehyde intermediate that is further reduced to the alcohol  Conversion of Acids into Esters (RCO2H-RCO2R′) Perhaps the most useful reaction of carboxylic acids is their conversion into esters by reaction with an alcohol. Called the Fischer esterification reaction - the substitution of -OH by -OR. The simplest method involves heating the carboxylic acid with an acid catalyst in an alcohol solvent. Apart from being a catalyst, the acid acts as a dehydrating agent, forcing the equilibrium to the right and resulting in a greater yield of ester.  Conversion of Acids into Acid Chlorides (RCO 2H RCOCl) Carboxylic acids are converted into acid chlorides by treatment with thionyl chloride, SOCl2. The reaction occurs by a nucleophilic acyl substitution pathway. The carboxylic acid is first converted into an acyl chlorosulfite intermediate, thereby replacing the -OH of the acid with a much better leaving group. The chlorosulfite then reacts with a nucleophilic chloride ion. Conversion of Acid to acid anhydrides With pyridine present in solution, a reaction between a carboxylic acid and an acid chloride yields an acid anhydride. The best method however for preparing acid anhydrides, is by a nucleophilic acyl substitution reaction of an acid chloride with a carboxylic acid anion  Conversion of Acids into Amides (RCO 2HRCONH2) Amides are carboxylic acid derivatives in which the acid -OH group has been replaced by a nitrogen substituent, -NH2, - NHR, or -NR2. Amides are difficult to prepare directly from acids by substitution with an amine because amines are bases, which convert acidic carboxyl groups into their unreactive carboxylate anions. Thus, the -OH must be activated by making it a better, nonacidic leaving group. In practice, amides are usually prepared by treating the carboxylic acid with dicyclohexylcarbodiimide (DCC) to activate it, followed by addition of the amine.  Amide are also synthesized Ammonia and amines react with acid chlorides to give amides NaOH, pyridine, or a second equivalent of amine is used to neutralize the HCl produced to prevent protonation of the amine. Chapter 20 37