1 Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates The functional group of...
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1 Nucleophilic substitution on carbonyl groups – Carboxylic acid derivates The functional group of a carboxylic acid is a carboxyl group –the general formula
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