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Home , Adipic acid, Crotonic acid, Malonic acid

Organic Lecture Series

Carboxylic

Chapter 17 111

Organic Lecture Series Structure • The functional group of a carboxylic is a carboxyl group

O O C COOH CO2 H OH OH Alternative representations for a carboxyl group

– the general formula for an aliphatic is RCOOH; that for an aromatic carboxylic acid is ArCOOH

222 Organic Lecture Series Nomenclature • IUPAC names: drop the -e from the parent alkane and add the suffix -oic acid

O HCOOH CH COOH 3 OH Methanoic acid Ethanoic acid 3-Methylbutanoic acid (Formic acid) () (Isovaleric acid)

– if the compound contains a -carbon double bond, change the infix -an- to -en- O O O OH OH OH

Propenoic acid t rans-2-Butenoic acid t rans-3-Phenylpropenoic acid () () () 333

Organic Lecture Series • The carboxyl group takes precedence over most other functional groups

OH O O O O H N OH OH 2 OH (R)-5-Hydroxyhexanoic 5-Oxohexanoic acid 4-Aminobutanoic acid acid O

O δδδ βββ OH γγγ ααα 5 3 1 OH O H 4 2 γγγ-hydroxybutyric Acid

GHB 444 Organic Lecture Series Nomenclature

– dicarboxylic acids : add the suffix -dioic acid to the name of the parent alkane containing both carboxyl groups

O O O HO OH HOOH O Ethanedioic acid Propanedioic acid () ()

O O O O HO HO OH HO OH OH O O Butanedioic acid Pentanedioic acid Hexanedioic acid () () () 555

Organic Lecture Series Nomenclature – if the carboxyl group is bonded to a ring, name the ring compound and add the suffix -carboxylic acid 2 1 COOH 3 HOOC COOH

2-Cyclohexenecarboxylic t rans-1,3-Cyclopentanedicarboxylic acid acid

– benzoic acid is the simplest aromatic carboxylic acid – use numbers to show the location of substituents COOH COOH COOH COOH OH COOH

COOH Benzoic 2-Hydroxybenzoic 1,2-Benzenedicarboxylic 1,4-Benzenedicarboxylic acid acid acid acid (Salicylic acid) (Phthalic acid) (Terephthalic acid) 666 Organic Lecture Series Nomenclature

– when common names are used, the letters α, β, γ, δ, etc. are often used to locate substituents

O O O δδδ γγγ βββ ααα H2 N OH 5 3 1 OH OH 4 2 NH2 4-Aminobutanoic acid (S)-2-Aminopropanoic acid (γγγ-Aminobutyric acid, GABA) [(S)-ααα-Aminopropionic acid; L-alanine]

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Organic Lecture Series Physical Properties • In the liquid and solid states, carboxylic acids are associated by bonding into dimeric structures

888 Physical Properties Organic Lecture Series • Carboxylic acids have significantly higher boiling points than other types of organic compounds of comparable molecular weight –they are polar compounds and form very strong intermolecular hydrogen bonds

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Physical Properties Organic Lecture Series • Carboxylic acids are more soluble in water than alcohols , ethers, , and of comparable molecular weight –they form hydrogen bonds with water molecules through their C=O and OH groups

101010 Organic Lecture Series Physical Properties

Molecular Boiling Weight Point

Structure Name (g/mol) (°C) (g/100 g H2O)

CH3 COOH Acetic acid 60.1 118 Infinite CH3 CH2 CH2 OH 1-Propanol 60.1 97 Infinite CH3 CH2 CHO Propanal 58.1 48 16

CH3 ( CH2 )2 COOH Butanoic acid 88.1 163 Infinite CH3 (CH2 ) 3 CH2 OH 1-Pentanol 88.1 137 2.3 CH3 ( CH2 )3 CHO Pentanal 86.1 103 Slight

CH3 ( CH2 )4 COOH Hexanoic acid 116.2 205 1.0 CH3 (CH2 ) 5 CH2 OH 1-Heptanol 116.2 176 0.2 CH3 ( CH2 )5 CHO Heptanal114.1 153 0.1

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Organic Lecture Series Physical Properties – water solubility decreases as the relative size of the hydrophobic portion of the molecule increases

121212 Organic Lecture Series Acidity • Carboxylic acids are weak acids

– values of p Ka for most aliphatic and aromatic carboxylic acids fall within the range 4 to 5 • The greater acidity of carboxylic acids relative to alcohols (both compounds that contain an OH group) is due to resonance stabilization of the carboxylate anion:

O O O H H 3 C OH H 3 C O H 3 C O 131313

Organic Lecture Series Acidity

– electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect

Formula: CH3 COOH ClCH2 COOH Cl2 CHCOOH Cl3 CCOOH Name: Acetic Chloroacetic Dichloroacetic Trichloroacetic acid acid acid acid K p a: 4.76 2.86 1.48 0.70 Increasing acid strength

141414 Organic Lecture Series

– the form of a carboxylic acid present in aqueous solution depends on the pH of the solution

O - O O OH- O OH - - R-C-OH R-C-OH + R-C-O + R-C-O H+ H predominant present in equal predominant species when concentrations when species when the pH of the the pH of the the pH of the solution is solution is equal to solution is 2.0 or less K 7.0 or greater the p a of the acid [A-] pH = pKa + log10 [HA] 151515

Organic Lecture Series

For organic acids in equilibrium: HA H+ + A-

Henderson-Hasselbalch equation: [A-] pH = pKa + log10 [HA] 161616 Reaction with Bases Organic Lecture Series

Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water- soluble salts

- + COOH + NaOH COO Na + H2 O H2 O Benzoic acid Sodium benzoate (slightly soluble (60 g/100 mL water) in water) Acid + Base + water 171717

Organic Lecture Series Reaction with Bases

• They also form water-soluble salts with ammonia and amines

- + COOH+ NH3 COO NH4 H2 O Benzoic acid Ammonium benzoate (slightly soluble (20 g/100 mL water) in water)

181818 Reaction with Bases Organic Lecture Series

• Carboxylic acids react with sodium bicarbonate and to form water-soluble salts and carbonic acid – carbonic acid, in turn, breaks down to and water

- + + CH3 COOH NaHCO3 CH3 COO Na + H2 CO3 H CO 2 3 CO2 + H2 O - + + + CH3 COOH NaHCO3 CH3 COO Na CO2 + H2 O

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Organic Lecture Series Preparation • Carbonation of Grignard reagents – treatment of a Grignard reagent with carbon dioxide followed by acidification gives a carboxylic acid O MgBr + C O Carbon dioxide

O O HCl C-O - [MgBr]+ C-OH + Mg2 + H2 O A magnesium carboxylate Cyclopentane- carboxylic acid 202020 Reduction Organic Lecture Series • The carboxyl group is very resistant to reduction – it is not affected by catalytic under conditions that easily reduce aldehydes and ketones to alcohols, and reduce alkenes and alkynes to alkanes; it

is not reduced by NaBH 4 • Lithium aluminum hydride reduces a carboxyl group to a 1°alcohol – reduction is carried out in diethyl ether, THF, or other nonreactive, aprotic solvent

O 1. LiAlH4 + COH CH2 OH+ LiOH Al(OH) 3 2. H2 O 4-Hydroxymethyl- cyclopentene 212121

Organic Lecture Series Selective Reduction – carboxyl groups are not affected by catalytic reduction under conditions that reduce aldehydes and ketones

O O OH O Pt OH + H2 OH 25°C, 2 atm 5-Oxohexanoic acid 5-Hydroxyhexanoic acid (racemic)

– nor are carboxyl groups reduced by NaBH 4 O O OH O NaBH4 C6 H5 OH C6 H5 OH H2 O 5-Oxo-5-phenylpentanoicacid 5-Hydroxy-5-phenylpentanoicacid (racemic) 222222 Organic Lecture Series Fischer Esterification • can be prepared by treating a carboxylic acid with an alcohol in the presence of an acid catalyst, commonly H2SO 4, ArSO 3H*, or gaseous HCl O O H2 SO4 OH + HOO + H2 O Ethanoic acid Ethyl ethanoate (Acetic acid) (Ethyl alcohol) (Ethyl acetate)

O * H 3 C S OH O Toluene Sulfonic Acid T s O H 232323

Organic Lecture Series Fischer Esterification Fischer esterification is an equilibrium reaction:  by careful control of experimental conditions, it is possible to prepare esters in high yield  if the alcohol is inexpensive relative to the carboxylic acid, it can be used in excess to drive the equilibrium to the right  alternatively, water can be removed by azeotropic distillation and a Dean-Stark trap

242424 Organic Lecture Series Fischer Esterification a key intermediate in Fischer esterification is the tetrahedral carbonyl addition intermediate formed by addition of ROH to the C=O group

H TCAI O

R COCH3 O H + H+ O H O

RCOCHCOH + HOCH3 R 3 + HOH

Refer to mechanism worksheet 252525

Organic Lecture Series Acid Chlorides • The functional group of an acid halide is a bonded to a halogen atom – among the acid halides, acid chlorides are by far the most common and the most widely used

OO O C-Cl - C- X CH3 CCl Functional group Acetyl Benzoyl of an acid halide chloride chloride

262626 Organic Lecture Series Acid Chlorides

– acid chlorides are most often prepared by treating a carboxylic acid with thionyl chloride

O O

OH + SOCl2 Cl + SO2 + HCl Butanoic acid Thionyl chloride Butanoyl chloride

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Organic Lecture Series Acid Chlorides • The mechanism for this reaction is divided into two steps.

Step 1: reaction with SOCl 2 transforms OH, a poor leaving group, into a chlorosulfite group, a good leaving group

O O OO R-C-O-H + Cl-S-ClR C O S Cl + H-Cl A chlorosulfite group

282828 Organic Lecture Series Acid Chlorides Step 2: attack of chloride gives a tetrahedral carbonyl addition intermediate, which collapses to give the acid chloride

O O R CO S Cl + Cl -

O:- O O - R C O S Cl R-C-Cl + SO2 + Cl Cl A tetrahedral carbonyl addition intermediate

Note: the reaction is irreversible 292929

Organic Lecture Series Decarboxylation

• Decarboxylation: loss of CO 2 from a carboxyl group – carboxylic acids, if heated to a very high temperature , undergo thermal decarboxylation O decarboxylation R-C-OH R-H + CO heat 2 – most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation

303030 Organic Lecture Series Decarboxylation The most important exceptions are carboxylic acids that have a carbonyl group beta to the carboxyl group i.e.- βββ keto-acids –this type of carboxylic acid undergoes decarboxylation on mild heating

O O O warm + βββ ααα OH CO2 3-Oxobutanoic acid (Acetoacetic acid) 313131

Organic Lecture Series Decarboxylation – thermal decarboxylation of a β-ketoacid involves rearrangement of six electrons in a cyclic six-membered transition state

H H OO O (1)O (2) O + C + CO O 2 O (A cyclic six-membered Enol of A transition state) a ketone

323232 Organic Lecture Series Decarboxylation – decarboxylation occurs if there is any carbonyl group beta to the carboxyl – malonic acid and substituted malonic acids, for example, also undergo thermal decarboxylation

O O O 140-150°C + HOCCH2 COH CH3 COH CO2 Propanedioic acid (Malonic acid)

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Organic Lecture Series

– thermal decarboxylation of malonic acids also involves rearrangement of six electrons in a cyclic six-membered transition state

H H OO O O (1) (2) O + C + CO2 HOO HO HO O A cyclic six-membered Enol of a A carboxylic transition state carboxylic acid acid

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