LECTURE № 6 Salts of carboxylic acids and saturated aminoacids aliphatic series as drugs
Chapter 21 Carboxylic Acids - San Diego Miramar Collegefaculty.sdmiramar.edu/choeger/Chapter 20...
Transcript of Chapter 21 Carboxylic Acids - San Diego Miramar Collegefaculty.sdmiramar.edu/choeger/Chapter 20...
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Chapter 20Carboxylic Acids
Chapter 20: Carboxylic Acids Slide 20-2
Introduction
• Carbonyl (-C=O) and hydroxyl (-OH) on the same carbon iscarboxyl group.
• Carboxyl group is usually written -COOH or CO2H.• Aliphatic acids have an alkyl group bonded to -COOH.• Aromatic acids have an aryl group.• Fatty acids are long-chain aliphatic acids.
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Chapter 20: Carboxylic Acids Slide 20-3
Common Names
• Many aliphatic acids have historical names.• Positions of substituents on the chain are labeled with Greek
letters.
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Chapter 20: Carboxylic Acids Slide 20-4
IUPAC Names
• Remove -e from alkane (or alkene) name, add -oic acid.• The carbon of the carboxyl group is #1.
CH3CH2CHC
Cl
OH
O
2-chlorobutanoic acid
PhC
H
C
H
COOH
trans-3-phenyl-2-propenoicacid (cinnamic acid)
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Chapter 20: Carboxylic Acids Slide 20-5
Naming Cyclic Acids
• Cycloalkanes bonded to -COOH are named ascycloalkanecarboxylic acids.
• Aromatic acids are named as benzoic acids.
COOH
CH(CH3)2
2-isopropylcyclopentanecarboxylic acid
COOH
OH
o-hydroxybenzoic acid(salicylic acid)
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Chapter 20: Carboxylic Acids Slide 20-6
Dicarboxylic Acids
• Aliphatic diacids are usually called by their common names(to be memorized).
• For IUPAC name, number the chain from the end closest to asubstituent.
• Two carboxyl groups on a benzene ring indicate a phthalicacid.
HOOCCH2CHCH2CH2COOH
Br
3-bromohexanedioic acidβ-bromoadipic acid
COOH
COOH
1,3-benzenedicarboxylic acid m-phthalic acid =>
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Chapter 20: Carboxylic Acids Slide 20-7
Structure of Carboxyl
• Carbon is sp2 hybridized.• Bond angles are close to 120°.• O-H eclipsed with C=O, to get overlap of π orbital with orbital
of lone pair on oxygen.
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Chapter 20: Carboxylic Acids Slide 20-8
Boiling Points
Higher boiling points than similar alcohols, due to dimerformation.
Acetic acid, b.p. 118°C =>
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Chapter 20: Carboxylic Acids Slide 20-9
Melting Points
• Aliphatic acids with more than 8 carbons are solids at roomtemperature.
• Double bonds (especially cis) lower the melting point. Notethese 18-C acids:Stearic acid (saturated): 72°COleic acid (one cis double bond): 16°CLinoleic acid (two cis double bonds): -5°C
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Chapter 20: Carboxylic Acids Slide 20-10
Solubility
• Water solubility decreases with the length of the carbonchain.
• Up to 4 carbons, acid is miscible in water.• More soluble in alcohol.• Also soluble in relatively nonpolar solvents like chloroform
because it dissolves as a dimer. =>
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Chapter 20: Carboxylic Acids Slide 20-11
Acidity
Chapter 20: Carboxylic Acids Slide 20-12
Resonance Stabilization
Important for anion
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Chapter 20: Carboxylic Acids Slide 20-13
Substituent Effects on Acidity
Chapter 20: Carboxylic Acids Slide 20-14
Salts of Carboxylic Acids
• Sodium hydroxide removes a proton to form the salt.• Adding a strong acid, like HCl, regenerates the carboxylic
acid.• “Solubility Switch”
CH3 C
O
OHNaOH
CH3 C
O
O
_Na
+
HCl
=>
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Chapter 20: Carboxylic Acids Slide 20-15
Naming Acid Salts
• Name the cation.• Then name the anion by replacing the
-ic acid with -ate.
CH3CH2CHCH2COO- K
+
Cl
potassium 3-chloropentanoatepotassium β-chlorovalerate =>
Chapter 20: Carboxylic Acids Slide 20-16
Properties of Acid Salts
• Usually solids with no odor.• Carboxylate salts of Na+, K+, Li+, and NH4
+ are soluble inwater.
• Soap is the soluble sodium salt of a long chain fatty acid.• Salts can be formed by the reaction of an acid with
NaHCO3, releasing CO2. =>
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Chapter 20: Carboxylic Acids Slide 20-17
Purifying an Acid
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Chapter 20: Carboxylic Acids Slide 20-18
Some Important Acids
• Acetic acid is in vinegar and other foods, used industriallyas solvent, catalyst, and reagent for synthesis.
• Fatty acids from fats and oils.• Benzoic acid in drugs, preservatives.• Adipic acid used to make nylon 66.• Phthalic acid used to make polyesters.
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Chapter 20: Carboxylic Acids Slide 20-19
IR Spectroscopy
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Chapter 20: Carboxylic Acids Slide 20-20
NMR Spectroscopy
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Chapter 20: Carboxylic Acids Slide 20-21
UV Spectroscopy
• Saturated carboxylic acids absorb very weakly around 200-215 nm.
• If C=C is conjugated with C=O, molar absorptivity =10,000 at 200 nm.
• An additional conjugated double bond increases theabsorption wavelength to 250 nm. =>
Chapter 20: Carboxylic Acids Slide 20-22
Mass Spectrometry
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Chapter 20: Carboxylic Acids Slide 20-23
Synthesis Review
• Oxidation of primary alcohols and aldehydes with chromicacid.
• Cleavage of an alkene with hot KMnO4 produces acarboxylic acid if there is a hydrogen on the double-bonded carbon.
• Cleavage of an alkyne with ozone or hot permanganate.• Alkyl benzene oxidized to benzoic acid by hot KMnO4 or
hot chromic acid. =>
Chapter 20: Carboxylic Acids Slide 20-24
Grignard Synthesis
Grignard reagent + CO2 yields a carboxylate salt.
CH3CH3CHCH2MgBr
CH3CO O CH3CH3CHCH2COO
-MgBr
+
CH3H+
CH3CH3CHCH2COOH
CH3
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Chapter 20: Carboxylic Acids Slide 20-25
Hydrolysis of Nitriles
Basic or acidic hydrolysis of a nitrile produces a carboxylicacid.
BrNaCN
CN
H+
H2O
COOH
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Chapter 20: Carboxylic Acids Slide 20-26
Acid Derivatives
• The group bonded to the acyl carbon determines the classof compound: -OH, carboxylic acid -Cl, acid chloride -OR’, ester -NH2, amide
• These interconvert via nucleophilic acyl substitution.=>
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Chapter 20: Carboxylic Acids Slide 20-27
Fischer Esterification
• Acid + alcohol yields ester + water.• Acid catalyzed for weak nucleophile.• All steps are reversible.• Reaction reaches equilibrium.
COOH
+ CH3CH2OH
H+ COCH2CH3
O
+ HOH
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Chapter 20: Carboxylic Acids Slide 20-28
Fischer Mechanism (1)
Protonation of carbonyl and attack of alcohol, a weaknucleophile.
COH
O
+
H+
+COH
OH
COH
OH
+CH3CH2OH
COH
OH
O H
CH2CH3
O
H
R
COH
OH
O
CH2CH3
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Chapter 20: Carboxylic Acids Slide 20-29
Fischer Mechanism (2)
Protonation of -OH and loss of water.
+H+
COH
OH
O
CH2CH3
C
OH
O
CH2CH3
H
OH
+O
H
R
C
O
CH2CH3
OH C
O
CH2CH3
O
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Chapter 20: Carboxylic Acids Slide 20-30
Diazomethane
• CH2N2 reacts with carboxylic acids to produce methyl estersquantitatively.
• Very toxic, explosive. Dissolve in ether.
C
O
OH +
C
O
OCH3 +CH2N2 N2
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Chapter 20: Carboxylic Acids Slide 20-31
Mechanism for Diazomethane
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Chapter 20: Carboxylic Acids Slide 20-32
Amides from Acids
• Amine (base) removes a proton from the carboxylic acid toform a salt (simple acid/base reaction!).
• Heating the salt above 100°C drives off steam and forms theamide.
C
O
OH +
C
O
O-
+NH3CH3
+
CH3NH2
heat
C
O
NHCH3
H2O
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Chapter 20: Carboxylic Acids Slide 20-33
Reduction to 1° Alcohols
• Use strong reducing agent, LiAlH4.• Borane, BH3 in THF, reduces carboxylic acid to alcohol, but
does not reduce ketone.
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Chapter 20: Carboxylic Acids Slide 20-34
Reduction to Aldehyde
• Difficult to stop reduction at aldehyde.• Use a more reactive form of the acid (an acid chloride) and a
weaker reducing agent, lithium aluminum tri(t-butoxy)hydride.
CCl
O
C
O
HLiAl[OC(CH3)3]3H
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Chapter 20: Carboxylic Acids Slide 20-35
Alkylation to Form Ketones
React 2 equivalents of an organolithium reagent with acarboxylic acid.
COOH 1)
2)
CH3CH2 Li2
H2O
C
O
CH2CH3
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Chapter 20: Carboxylic Acids Slide 20-36
Acid Chlorides
• An activated form of the carboxylic acid.• Chloride is a good leaving group, so undergoes acyl
substitution easily.• To synthesize acid chlorides use thionyl chloride or oxalyl
chloride with the acid.
C
O
OHC
O
C
O
Cl Cl+
C
O
Cl
+ + +HCl CO CO2
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Chapter 20: Carboxylic Acids Slide 20-37
Esters from Acid Chlorides
• Acid chlorides react with alcohols to give esters in goodyield.
• Mechanism is nucleophilic addition of the alcohol to thecarbonyl as chloride ion leaves, then deprotonation.
CCl
O
+ CH3OH
COCH3
O
+ HCl
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Chapter 20: Carboxylic Acids Slide 20-38
Amides from Acid Chlorides
• Acid chlorides react with ammonia and amines to giveamides.
• A base (NaOH or pyridine) is added to remove HCl by-product.
CCl
O
+ CH3NH2
CNHCH3
O
NaOH
NaCl H2O+ +
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Chapter 20: Carboxylic Acids Slide 20-39
End of Chapter 20
Homework: Practice naming anywhere you can!33, 35, 36, 39, 42-44, 47, 48, 49