Embed Size (px)
Citation preview
1
5-1
Carboxylic Acids and Their Derivatives
5-2
Nomenclature1. Carboxylic Acids:
17.1-2
F
2. Carboxylic Acid Ester:
3. Carboxylic Anhydrides:
F
F
R
O
OH
alkanoic acid
OH
O
Example:[RCOOH]
R
O
OR'
alkyl alkanoate
O
O
Example:[RCOOR']
OH
R
O
O
alkanoic anhydride
O
O
Example:[(RCO)2O]R
O
O
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
2
5-3
4. Acyl Chlorides:
17.1-2
F
5. Amides:
6. Nitriles:
F
F
R
O
Cl
alkanoyl chloride
Cl
O
Example:[RCOCl]
R
O
NR2'
N,N-alkyl alkanamide
N
O
Example:[RCONR2']
OH
Alkane nitrile
CNExample:
[RCN]R C N
5-4
Important common names of carboxylic acids:
17.1-2
F
O
OHacetic acid
HO
OOH
Osuccinic acid
H
O
OHformic acid
O
OHpropionic acid
O
OHbutyric acid
COOH
benzoic acid
HO OHO
oxalic acidO
HO
O
malonic acid
OH
O
HO
OOH
Ofumaric acid
HO
O
maleic acid
O OH
COOH
phthalic acidCOOH
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
3
5-5
Applying common names to derivatives:
17.1-2
F
O
OH
acetic acid
HO
OOH
Osuccinic acid
O
Cl Cl
OCl
OO
O
OO
O
OO
OCH3 H3CO
OOCH3
OO
NH2 H2N
ONH2
O
H3C CN NC CN
5-6
Acidity of Carboxylic AcidIn aqueous solution, carboxylic acids dissociate into the carboxylate anion and hydronium ion:
17.2C
The acidity (Ka) increases with increasing stability of the carboxylate anion:
R
O
OHalkanoic acid
+ H2OR
O
Oalkanoate anion
+ H3OKa
O
OH
O
OHClO
OHCl
Cl
O
OHCl
ClCl
pKa 4.76 2.86 1.48 0.70
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
4
5-7
Problem: Order following carboxylic acids with increasing pKa.
O
OH
O
OHF
O
OHCl
O
OHCl
5-8
Preparation of Carboxylic Acids1. Oxidation Reactions:
17.3
R R'
1. KMnO4, NaOH, heat
2. H3O+
1. O3
2. H2O2
R O
OH R'O
OH+
R OH
1. KMnO4, NaOH, heat
2. H3O+ R OH
O
Na2Cr2O7
H2SO4
or R H
O
R O
OH R'O
OH+
R OH
O
R H
O 1. Ag(NH3)2+
2. H3O+ R OH
O
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
5
5-9
1. Oxidation Reactions (continued):
17.3
2. Hydrolysis of Nitriles:
3. Carboxylation of Grignard Reagents:
F
F
F
1. KMnO4, NaOH, heat
2. H3O+R
R
OH
O
1. NaOH, H2O, heat
2. H3O+ R OH
O
HCl, H2O
heat R OH
OR C N
1. CO2
2. H3O+ R OH
OR MgBr
5-10
Problem: How would you carry out each of the following transformation?
Cl Cl
COOH
OH
O
OH
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
6
5-11
Nucleophilic Addition-Elimination at the Acyl CarbonNucleophilic Addition (Topic 3, Slide 3-23):
17.4
Nucleophilic Addition-Elimination:
If one of the carbonyl group substituents is a good leaving group (L), the addition reaction is followed by an elimination step:
Leaving group ability increases with decreasing pKa of the conjugate acid of the leaving group.
R R
O+ Nu
R R
O
Nu
H Nu
R R
O
Nu
HNu+
R L
O+ Nu
R L
O
NuR Nu
OL+
5-12
Relative Reactivity of Acyl CompoundsThe reactivity of the substitution reaction directly parallels the leaving group ability of L:
17.4A
R
O
Cl
acyl chloride
R
O
O R
O
acid anhydride
R
O
OR'
ester
R
O
NH2
amide
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
7
5-13
Transformation of Acid Derivatives
17.4A
R
O
ClR
O
OH
R C N
R
O
O R
O
R
O
OR' R
O
NH2
R
O
OH R
O
O R
O
R
O
OR' R
O
NH2
R
O
OH R
O
OR' R
O
NH2
R
O
OH R
O
NH2
R
O
OH
5-14
Acyl Chlorides
17.5A
Synthesis:
Mechanism:
FR
O
ClR
O
OHSOCl2
other reagents: PCl3 or PCl5
+ + SO2 + HCl
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
8
5-1517.5B
Reactions of Acyl Chlorides:
Hydrolysis in aqueous solution regenerates the acid:
F
F
F
F
F
R
O
Cl+
R' O
O
Na
R
O
Cl+ R' OH
R
O
Cl+ R' NH2
R
O
Cl
R
O
Cl
H2O
NaOH, H2O
5-16
Carboxylic Acid Anhydrides
17.6
Synthesis:Cyclic anhydrides formed by dehydration of carboxylic acids at high temperature:
General method: from acyl chlorides (slide 30-15):
F
OHOH
O
O
300°CO
O
Osuccinic acid
R
O
Cl+
R' O
O
Na
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
9
5-1717.6B
Reactions of carboxylic acid anhydrides:
Hydrolysis in aqueous solution regenerates the acid:
F
F
F
F
R
O
O+ R' OH
+ R' NH2
R
O
R
O
O R
O
H2O
NaOH, H2O
R
O
O R
O
R
O
O R
O
5-18
Esters
17.7A
Synthesis:
Mechanism:
Acid-catalyzed reaction of carboxylic acids with alcohols (Fischer Esterification):
FR
O
OR'R
O
OH+ + H2OR' OH
cat. H2SO4
O
OH H O H
H
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
10
5-1917.7B
Esters from acid chlorides (slide 3-15):
Esters from carboxylic acid anhydrides (slide 3-17):
R
O
OR'R
O
Cl+ R' OH
pyridine+ HCl
R
O
OR'+ R' OH
R
O
O R
O +HO R
O
5-2017.7B
Reactions of Esters:Transesterification:
Amidation (Aminolysis):
Base promoted hydrolysis (Saponification):
F
F
F
R
O
OCH3
R' OHHA, heat
+
R
O
OCH3R' NH2+
heat
R
O
OCH3
NaOH
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
11
5-21
Saponification
17.7B
Natural soaps are sodium or potassium salts of fatty acids, originally made by boiling animal fat together with potash (potassium hydroxide). Upon hydrolysis of the fats and oils, glycerol and crude soap is formed:
O
O
O
O
O
O
KOH
heat
OH
OH
OH +
OKO
OKO
OKO
5-22
Problem: How could you prepare ethyl 4-aminobenzoate (benzocaine)?
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
12
5-23
Problem: What is the major product obtained from the following reaction?
HO OH
O
H2SO4 ?
5-24
Problem: Explain the following observations:
∆? + H2O
OH
HOOC
∆no reactionHOOC OH
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
13
5-25
Amides
17.8A,E
Synthesis:Carboxylic acids react with aqueous ammonia to form ammonium salts. Further reaction does not occur, unless the dried salt is heated:
F
DCC-promoted amide synthesis from carboxylic acids (used in peptide chemistry):
F
R
O
OR
O
OH+ NH3
NH4
R
O
O NH4
heat
R
O
NH2
+ H2O
R
O
OHR' NH2
DCC+
R
O
NHR'
N C N
dicyclohexylcarbodiimide
5-2617.8A,B,C,D
Amides from acid chlorides (slide 3-19):
Amides from carboxylic acid anhydrides (slide 3-17):
Amides from carboxylic acid esters (slide 3-17):
R
O
NHR'R
O
Cl+ R' NH2
DIPEA+ HCl
R
O
NHR'+ R' NH2
R
O
O R
O +HO R
ODIPEA
R
O
OCH3
R' NH2+heat
R
O
NHR'+ CH3OH
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
14
5-2717.8G, 18.8H
Reactions of Amides:Dehydration:
Base promoted hydrolysis:
F
F
F
R
O
NH2
P2O5
R
O
NH2
1. NaOH
2. H3O+ R
O
OH
5-28
Problem: Propose a synthesis of N,N-diethyl-m-toluamide (DEET), the active ingredient in a number of commercial insect repellants.
O N
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
15
5-29
Reactions of Acid Derivatives with Reducing Agents and Organometallics
1.1. Acid Chlorides: Reduction
F
Mechanism:
F
R
O
Cl
1. LiAlH4
2. H3O+R OH
R
O
Cl
1. LiAlH(tBuO)3, –78°C
2. H3O+ R H
O
5-30
1.2. Acid Chlorides: Reaction with Grignard and organocopper reagents
F
Mechanism:
F
R
O
Cl
1. R'MgBr
2. H3O+
R
O
Cl
1.R'2CuLi
2. H3O+
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
16
5-31
Problem: 3-Hexanone revisited. Provide a synthesis of 3-hexanone from alcohols with three or fewer carbon atoms
Opreviously
Br BrHH
5-32
2.1. Esters: Reduction
F
F
2.2. Esters: Reaction with Grignard reagents
F
R
O
OCH3
1. LiAlH4
2. H3O+
R
O
OCH3
1. DIBAL-H –78°C
2. H3O+
R
O
OCH3
1. 2 eq CH3MgBr
2. H3O+
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
17
5-33
Problem: Propose a synthesis of 2-methyl-2-hexanol from pentanoic acid.
5-34
3.1. Amides: Reduction
F
F
F
Mechanism:
R
O
NH2
1. LiAlH4
2. H3O+
R
O
NH
1. LiAlH4
2. H3O+
R
O
N1. LiAlH4
2. H3O+
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
18
5-35
4.1. Nitriles: Reduction
F
F
4.2. Nitriles: Reaction with Grignard reagents
F
1. LiAlH4
2. H3O+
1. DIBAL-H –78°C
2. H3O+
R C N
R C N
1. CH3MgBr
2. H3O+R C N
5-36
Problem: Propose a synthesis of 3-chlorobenzonitrile
CN
Cl
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
19
5-37
Problem: Propose a synthesis of novocaine (procaine)
O
O
H2N
N
CHEM 2312 Fall 2017 Notes: C.J. Fahrni
![[PPT]Chapter 20: Carboxylic Acid Derivatives - El Paso … · Web viewNomenclature Anhydrides Symmetrical anhydrides are named by changing the acid ending of the carboxylic acid to](https://img.pdfslide.us/doc/110x75/5b855a487f8b9aea498e3be1/pptchapter-20-carboxylic-acid-derivatives-el-paso-web-viewnomenclature.jpg)
