1 Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates The functional group of...
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- Slide 1
- 1 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates The functional group of a carboxylic acid is a carboxyl
group the general formula of an aliphatic carboxylic acid is RCOOH
that of an aromatic carboxylic acid is ArCOOH
- Slide 2
- 2 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates e oic acidIUPAC names: drop the -e from the parent alkane
and add the suffix - oic acid anen if the compound contains a
carbon-carbon double bond, change the infix -an- to -en-
- Slide 3
- 3 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates The carboxyl group takes precedence over most other
functional groups
- Slide 4
- 4 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates dioic acid dicarboxylic acids: add -dioic acid to the
name of the parent alkane containing both carboxyl groups there is
no need to use numbers to locate the carboxyl groups; they can only
be on the ends of the chain
- Slide 5
- 5 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates carboxylic acid if the carboxyl group is bonded to a
ring, name the ring compound and add the suffix -carboxylic acid
benzoic acid is the simplest aromatic carboxylic acid use numbers
to show the location of substituents
- Slide 6
- 6 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates when common names are used, the letters etc. are often
used to locate substituents keto aceto group in common
nomenclature, keto indicates the presence of a ketone, and CH 3 CO-
is named an aceto group
- Slide 7
- 7 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates water solubility decreases as the relative size of the
hydrophobic portion of the molecule increases 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 Carboxylic acids
are more soluble in water than alcohols, ethers, aldehydes, and
ketones of comparable molecular weight they form hydrogen bonds
with water molecules through their C=O and OH groups
- Slide 8
- 8 Carboxylic acids are weak acids values of pKa for most
aliphatic and aromatic carboxylic acids fall within the range 4 to
5 the greater acidity of carboxylic acids relative to alcohols,
both of which contain an OH group, is due to resonance
stabilization of the carboxylate anion Nucleophilic substitution on
carbonyl groups Carboxylic acid derivates electron-withdrawing
substituents near the carboxyl group increase acidity through their
inductive effect
- Slide 9
- 9 the acid-strengthening effect of a halogen substituent falls
off rapidly with increasing distance from the carboxyl group
Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates
- Slide 10
- 10 Carboxylic acids, whether soluble or insoluble in water,
react with NaOH, KOH, and other strong bases to give water-soluble
salts They also form water-soluble salts with ammonia and amines
Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates
- Slide 11
- 11 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates Higher reactivity of carbonyl!!!
- Slide 12
- 12 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates
- Slide 13
- 13 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates Mechanism:
- Slide 14
- 14 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates Leaving groups:
- Slide 15
- 15 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates
- Slide 16
- 16 Nucleophilic substitution on carbonyl groups Carboxylic acid
derivates Synthesis of anhydrides
- Slide 17
- 17 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Acid + Alcohol -> Ester The functional group of an
ester is an acyl group bonded to -OR or -OAr name the alkyl or aryl
group bonded to oxygen followed by the name of the acid -ic
acid-ate change the suffix -ic acid to -ate Excess
- Slide 18
- 18 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Acid + Alcohol -> Ester Excess
- Slide 19
- 19 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Acid + Alcohol -> Ester base-catalysed esterfication
-> does not work with acid + alcohol Pyridine as proton
catcher
- Slide 20
- 20 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Acid + Alcohol -> Ester Transesterfication
- Slide 21
- 21 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Acid + Alcohol -> Ester Transesterfication
- Slide 22
- 22 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydroxyacid -> Lactone Lactone: a cyclic ester -ic
acid -olactone IUPAC: name the parent carboxylic acid, drop the
suffix -ic acid, and add -olactone the location of the oxygen atom
on the carbon chain is commonly indicated by a Greek letter
- Slide 23
- 23 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydroxyacid -> Lactone
- Slide 24
- 24 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydroxyacid -> Lactone
- Slide 25
- 25 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydrolysis of carboxylic acid derivates
- Slide 26
- 26 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydrolysis of carboxylic acid derivates
- Slide 27
- 27 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydrolysis of carboxylic acid derivates
- Slide 28
- 28 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydrolysis of carboxylic acid derivates
- Slide 29
- 29 Nucleophilic substitution on carbonyl groups Oxygen as
nucleophile Hydrolysis of carboxylic acid derivates Amides
(Peptides and Proteins)
- Slide 30
- 30 Nucleophilic substitution on carbonyl groups Sulfur as
nucleophile Thiols + Carboxylic acid derivates -> Thioacids and
Thioesters Reactivity increased (compared to formation of ester):
1.Sulfur better nucleotide than oxygen 2.RS - better leaving group
than RO -
- Slide 31
- 31 Nucleophilic substitution on carbonyl groups Sulfur as
nucleophile Thiols + Carboxylic acid derivates -> Thioacids and
Thioesters
- Slide 32
- 32 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Amines (1, 2, 3) + Carboxylic acid (derivates) ->
Amides -> with Carboxylic acid
- Slide 33
- 33 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Amines (1, 2, 3) + Carboxylic acid (derivates) ->
Amides -> with Carboxylic acid derivates
- Slide 34
- 34 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Amines (1, 2, 3) + Carboxylic acid (derivates) ->
Amides -> with esters
- Slide 35
- 35 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Amines (1, 2, 3) + Carboxylic acid (derivates) ->
Amides
- Slide 36
- 36 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Aminoacids -> Lactams (cyclic amides) -ic acidlactam
- name the parent carboxylic acid, drop the suffix -ic acid and add
lactam - the location of the nitrogen atom in the ring is commonly
indicated by a Greek letter, , , etc.
- Slide 37
- 37 Nucleophilic substitution on carbonyl groups Nitrogen as
nucleophile Aminoacids -> Lactams (cyclic amides) Penicillins
and Cephalosporins are member of a family of -lactam
antibiotics
- Slide 38
- 38 Nucleophilic substitution on carbonyl groups Hydride as
nucleophile Reduction of carboxylic acid derivates -> Alkohols
Lithium aluminium hydride (LAH) -> strong hydrid donor Sodium
borohydride (NaBH4) -> weaker hydrid donor LAH reduces ->
acyl halides, anhydrides, esters, and acids -> primary
alcohol
- Slide 39
- 39 Nucleophilic substitution on carbonyl groups Hydride as
nucleophile Reduction of carboxylic acid derivates -> Alkohols
Lithium aluminium hydride (LAH) -> strong hydrid donor ->
reduces almost all carboxylic acid derivates Sodium borohydride
(NaBH4) -> weaker hydrid donor -> reduces acyl halides,
ketons, aldehydes
- Slide 40
- 40 Nucleophilic substitution on carbonyl groups Hydride as
nucleophile Reduction of Amides -> Amines -> different
mechanism!!!
- Slide 41
- 41 Nucleophilic substitution on carbonyl groups Hydride as
nucleophile Reduction of Amides -> Amines -> different
mechanism!!!
- Slide 42
- 42 Nucleophilic substitution on carbonyl groups Carbon as
nucleophile Carboxylic acid derivates + Grignard ->
Alcohols
- Slide 43
- 43 Nucleophilic substitution on derivates of sulfuric and
phosphoric acids
- Slide 44
- 44 Nucleophilic substitution on derivates of sulfuric and
phosphoric acids Sulfuric acid derivates
- Slide 45
- 45 Nucleophilic substitution on derivates of sulfuric and
phosphoric acids Phosphoric acid derivates
- Slide 46
- 46 Nucleophilic substitution on derivates of sulfuric and
phosphoric acids Phosphoric acid derivates
- Slide 47
- 47 Nucleophilic substitution on derivates of sulfuric and
phosphoric acids Phosphoric acid derivates