Post on 03-Feb-2022
Reações de ácidos carboxilícos e
derivados
HN
N
Cl
O
N3
HO
N
NH
O
O
CH3
NH
HN
Br
O
O
Br
N
OO
N
H
H
H
H
HO
MeOO
OOMe
OMe
O
OMe
O
HO
O
O OOHO
N
CO2H
S
O
HN
NH
H
HHHO
N
N
CF3
CH3H2NSO2
Cl
Cl Cl
OH
Ácidos e derivados
Ésteres
Aminas
Anidridos
Haletos de ácidos
Anidridos cíclicos com anéis de 5 e 6 membros são preparados
pela desidratação de ácidos dicarboxilícos
Anidridos cíclicos são preparados a partir de
1,n-diácidos
OH
OH
O
O
tetracloroetilenosolvente
130 C
desidratação
O
O
O
Anidrido acético
Anidrido ftálico Anidrido malêico
Anidridos ácidos são precursores importantes
O
CH3OH3C
O
O
O
O
O
O
O
Acetato de 3-metilbutila
" acetato de isopentila" e “acetato de isoamila"
odor característico de bananas
O
OCH3 CH3
CH3
Frequentemente, os ésteres são encontrados como produtos
naturais
Ésteres
Triestearina: Gorduras animais e vegetais
O
O
O
CH3(CH2)16
O
O
(CH2)16CH3
(CH2)16CH3
O
Óleos e gorduras são misturas de triésteres de glicerila
(Z)-5-Tetradecen-4-olida
(feromônio sexual da fêmea do besouro japônes)
O
O
H
H
CH2(CH2)6CH3
As lactonas são ésteres cíclicos
Carboxylic Acids and Derivatives:
Nucleophilic Acyl Substitution
O
XR
O
NucR
Nuc-H
or
Nuc-
The extent to which the lone pair on X can be delocalized
into C=O depends on:
1) the electronegativity of X
2) how well the lone pair orbital of X interacts
with the orbital of C=O
Deslocalização eletrônica e o grupo
carboxila
O
XR
O
XR
O
XR
ESTERIFICAÇÃO
CH3C
O
Cl
CH3C
O
OCCH3
O
CH3C
O
SCH2CH3
CH3C
O
OCH2CH3
CH3C
O
NH2
Most
reactive
Least
reactive
Least
stabilized
Most
stabilized
Orbital Overlap in Carboxylic Acid
Derivatives
O
X
R
O
X
R
The p-* orbital interactioncan be represented in termsof resonance
O CX
R
Lone PairEmpty *
orbitial
Orbitals Overlap
1) the electronegativity of X
2) how well the lone pair orbital of X interacts with the
orbital of C=O
Orbital Overlap in Carboxylic Acid
Derivatives
NitrogenLone Pair
Empty *
Orbital of
CO group
Interaction of filled and empty orbitals lowers the energy of thesystem
New, lower
energy orbital
New, higher
energy orbital
O CX
R
Lone PairEmpty *
orbitial
Orbitals Overlap
Esterification
H+ (catalyst)
(a reversible
condenstation
reaction)
Ester
O
R OH
R OH
O
R O
R
AlcoholCarboxylic Acid
H2O
Fischer Esterification - A Reversible Process
Mechanism of Acid-Catalyzed Esterification
The mechanism involves two stages:
1) formation of tetrahedral intermediate
(3 steps)
2) dissociation of tetrahedral intermediate
(3 steps)
Mechanism of Fischer Esterification
tetrahedral intermediate in esterification
of benzoic acid with methanol
OCH3
HO OH
methanol adds to the
carbonyl group of the
carboxylic acid
the tetrahedral
intermediate is
analogous to a
hemiacetal
Stage One
Formation of Tetrahedral Intermediate
OCH3
HO OH
OH
O
HO CH3
H+
this stage corresponds
to an acid-catalyzed
dehydration
Stage Two
Collapse of Tetrahedral Intermediate to Ester
OCH3
HO OH
O
O
H+
CH3
H2O
Mechanism of formation
of
tetrahedral intermediate
Step 1
C
O
O H
••••
••
••
O ••+
H
CH3
H
••
C
O
O H
••
••
+ H ••O •
•
CH3
H
Step 1
••
C
O
O H
••
••
+ H
carbonyl oxygen is
protonated because
cation produced is
stabilized by electron
delocalization
(resonance)
C
O
O H
••••
+
H
••
Step 2
••
C
O
O H
••
••
+ H
••O •
•
CH3
H
C
OH
OH
••••
••
••
O ••
+CH3
H
Step 3
••
C
OH
OH
••••
••
O ••
CH3
H
+
••O •
•
CH3
H
O ••
CH3
H
H+
••
C
OH
OH
••••
••
O ••
CH3
••
Tetrahedral intermediate
to
ester stage
Step 4
O ••
CH3
H
H+••
C
OH
O
••••
••
OCH3••
••
H
••
C
OH
O
••••
OCH3••
••
H H
+ •• O •
•
CH3
H
Step 5
••
C
OH
O
••••
OCH3••
••
H H
+
O••H H
••+
C
OH••
••
OCH3
••
••
+
Step 5
C
OH••
••
OCH3
••
••
+
C
OH••
OCH3
••
••
+
Step 6
C
O••
OCH3
••
••
+ H
O••
H CH3••
+OH CH3••
H
C
O••
OCH3
••
••
••
Activation of carbonyl group by protonation of
carbonyl oxygen
Nucleophilic addition of alcohol to carbonyl group
forms tetrahedral intermediate
Elimination of water from tetrahedral intermediate
restores carbonyl group
Key Features of Mechanism
20.1
Nomenclature of Carboxylic Acid Derivatives
Name the acyl group and add the word chloride, fluoride, bromide, or iodide as appropriate.
Acyl chlorides are, by far, the most frequently encountered of the acyl halides
Nomenclature of Acyl Halides
O
XR
X = Halogen
acetyl chloride
3-butenoyl chloride
p-fluorobenzoyl bromide
Nomenclature of Acyl Halides - Examples
O
ClH3C
O
Cl
O
Br
F
When both acyl groups are the same, name the acid
and add the word anhydride
When the groups are different, list the names of the
corresponding acids in alphabetical order and add the
word anhydride
Nomenclature of Acid Anhydrides
O
OR R'
O
acetic anhydride
benzoic anhydride
benzoic heptanoic anhydride
Nomenclature of Acid Anhydrides - Examples
O
OH3C CH3
O
O
O
O
O
O
O
CH3
name as alkyl alkanoates
cite the alkyl group attached to oxygen first (R')
name the acyl group second; substitute the suffix
-ate for the -ic ending of the corresponding acid
Nomenclature of Acid Esters
O
ORR'
ethyl acetate
methyl propanoate
2-chloroethyl benzoate
Nomenclature of Acid Esters - Examples
O
OCH3CH3
O
OCH3 CH3
O
O
Cl
identify the corresponding carboxylic acid
replace the -ic acid or -oic acid ending by -amide
Nomenclature of Primary Amides
O
NH2R
acetamide
3-methylbutanamide
benzamide
Nomenclature of Primary Amides - Examples
O
NH2H3C
O
NH2H3C
H3C
NH2
O
name the amide as before
precede the name of the amide with the name of the
appropriate group or groups
precede the names of the groups by the letter N- (standing
for nitrogen and used as a locant)
and
Nomenclature of Secondary & Tertiary Amides
O
NH
RR
O
NRR
R'
N-methylacetamide
N-isopropyl-N-methylbutanamide
N,N-diethylbenzamide
Nomenclature of Secondary & Tertiary Amides
O
N CH3
CH3
H3C N
O
CH3
CH3
CH3
O
NH
H3CCH3
add the suffix -nitrile to the name of the parent hydrocarbon
chain (including the triply bonded carbon of CN)
or: replace the -ic acid or -oic acid name of the
corresponding carboxylic acid by -onitrile
or: name as an alkyl cyanide (functional class name
Nomenclature of Cyanides
R C N
CH3C N
ethanenitrile
or: acetonitrile
or: methyl cyanide
C6H5C N benzonitrile
NC
CH3CHCH3 2-methylpropanenitrile
or: isopropyl cyanide
Nomenclature of Cyanides
20.2
Structure and Reactivity
of
Carboxylic Acid Derivatives
The key to managing the information in
this chapter is the same as always:
structure determines properties.
---------------
The key structural feature is how well the
carbonyl group is stabilized.
---------------
The key property is reactivity in nucleophilic
acyl substitution.
Three Keys to Understanding the
Chemistry of Carboxylic Acids Derivatives
The main structural feature that distinguishes acyl
chlorides, anhydrides, thioesters, esters, and amides is
the interaction of the substituent with the carbonyl
group. It can be represented in resonance terms as:
Electron Delocalization and the Carbonyl Group
O
XR
O
XR
O
XR
lone pair orbital
of substituent
Orbital Overlap in Carboxylic Acid Derivatives
electron pair of substituent delocalized into
carbonyl orbital
Orbital Overlap in Carboxylic Acid Derivatives
Acyl chlorides have the least stabilized carbonyl
group
Delocalization of lone pair of Cl into C=O group is
not effective because C—Cl bond is too long
••
C
O
R
Cl••
••
••
••
••
C
O
R
Cl••
••
••
••
+
–
Orbital Overlap in Acyl Chlorides
RCCl
O
least stabilized C=O
most stabilized C=O
lone pair donation from oxygen stabilizes the
carbonyl group of an acid anhydride
the other carbonyl group is stabilized in an
analogous manner by the lone pair
••CR
O••
••
O••
C
O••
••
R
O••
••
••••
+
–
CR
O ••
O••
CR
Orbital Overlap in Acid Anhydrides
RCOCR'
O ORCCl
O
least stabilized C=O
most stabilized C=O
Sulfur (like chlorine) is a third-row element.
Electron donation to C=O from third-row elements
is not very effective.
Resonance stabilization of C=O in thioesters is
not significant.
••••
+
–
CR
O ••
SR'••
O••
••
••CR SR'
••
Orbital Overlap in Thioesters
RCOCR'
O ORCCl
O
least stabilized C=O
most stabilized C=O
RCSR'
O
lone pair donation from oxygen stabilizes the
carbonyl group of an ester
stabilization greater than comparable stabilization
of an anhydride or thioester
••••
+
–
CR
O ••
OR'••
O••
••
••CR OR'
••
Orbital Overlap in Esters
RCOCR'
O ORCCl
O
RCOR'
O
least stabilized C=O
most stabilized C=O
RCSR'
O
lone pair donation from nitrogen stabilizes the
carbonyl group of an amide
N is less electronegative than O; therefore,
amides are stabilized more than esters and
anhydrides
••••
+
–
CR
O ••
NR'2
O••
••
••CR NR'2
Orbital Overlap in Amides
amide resonance imparts significant double-bond
character to C—N bond
activation energy for rotation about C—N bond
is 75-85 kJ/mol
C—N bond distance is 135 pm in amides versus
normal single-bond distance of 147 pm in amines
••••
+
–
CR
O ••
NR'2
O••
••
••CR NR'2
Orbital Overlap in Amides
RCOCR'
O ORCCl
O
RCOR'
O
RCNR'2
O
least stabilized C=O
most stabilized C=O
RCSR'
O
very efficient electron delocalization and dispersal
of negative charge
maximum stabilization
O••
••
••CR
–O••
••
••••
–
CR
O ••
••••
O
Orbital Overlap in Carboxylate Ions
RCOCR'
O ORCCl
O
RCOR'
O
RCNR'2
O
RCO–
O
least stabilized C=O
most stabilized C=O
RCSR'
O
Stabilization
very small
small
large
moderate
Relative rate
of hydrolysis
1011
107
<10-2
1.0
The more stabilized
the carbonyl group,
the less reactive it
is.
Reactivity is Related to Structure
O
OR R
O
O
OR
R'
O
NR
R'
R'
O
ClR
In general:
O••
••
CR X
+ HY
O••
••
CR Y
+ HX
Reaction is feasible when a less stabilized
carbonyl is converted to a more stabilized
one (more reactive to less reactive).
Nucleophilic Acyl Substitution
RCOCR'
O ORCCl
O
RCOR'
O
RCNR'2
O
RCO–
O
RCSR'
O
most reactive
least reactive
a carboxylic acid
derivative can be
converted by
nucleophilic acyl
substitution to any other
type that lies below it in
this table
20.3
General Mechanism
for
Nucleophilic Acyl Substitution
O••
••
CR X
+ HNu
O••
••
CR Nu
+ HX
Reaction is feasible when a less stabilized
carbonyl is converted to a more stabilized
one (more reactive to less reactive).
Nucleophilic Acyl Substitution
involves formation and dissociation
of a tetrahedral intermediate
O••
••
CR X
HNu
C
ROH
X
Nu
O••
••
CR Nu
-HX
Both stages can involve several elementary steps.
Mechanism of Nucleophilic Acyl Substitution
first stage of mechanism (formation of tetrahedral
intermediate) is analogous to nucleophilic addition
to C=O of aldehydes and ketones
O••
••
CR X
HNu
C
ROH
X
Nu
Mechanism of Nucleophilic Acyl Substitution
second stage is restoration of C=O by elimination
O••
••
CR X
HNu
C
ROH
X
Nu
O••
••
CR Nu
-HX
complicating features of each stage involve
acid-base chemistry
Mechanism of Nucleophilic Acyl Substitution
O••
••
CR X
HNu
C
ROH
X
Nu
O••
••
CR Nu
-HX
Acid-base chemistry in first stage is familiar in that
it has to do with acid/base catalysis of nucleophilic
addition to C=O.
Mechanism of Nucleophilic Acyl Substitution
O••
••
CR X
HNu
C
ROH
X
Nu
O••
••
CR Nu
-HX
Acid-base chemistry in second stage concerns
form in which the tetrahedral intermediate exists
under the reaction conditions and how it dissociates
under those conditions.
Mechanism of Nucleophilic Acyl Substitution
tetrahedral intermediate (TI)
C
RO
X
Nu••
H••
••
••
C
RO
X
Nu••
H••
••
H +
Conjugate acid of tetrahedral
intermediate (TI+)
••
O••
••
C
R
X
Nu
••••
–
Conjugate base of tetrahedral
intermediate (TI–)
The Tetrahedral Intermediate
••
C
RO
X
Nu••
H ••
H+
+B—H +C
O
R Nu ••
••••
+ X H••
B••
Dissociation of Protonated Tetrahedral Inter.
B••
••
C
RO
X
Nu••
H ••
••
+B—H +C
O
R Nu ••
••••
+ X••
••–
Dissociation of Neutral Tetrahedral Inter.
C
O
R Nu ••
••••
+ X••
••–
••
C
RO
X
Nu••
••
••
••
–
Dissociation of Anionic Tetrahedral Inter.
Nucleophilic Substitution
in Acyl Chlorides
from carboxylic acids and thionyl chloride
(CH3)2CHCOH
OSOCl2
heat(CH3)2CHCCl
O
+ SO2 + HCl
(90%)
Preparation of Acyl Chlorides
RCOCR'
O ORCCl
O
RCOR'
O
RCNR'2
O
RCO–
O
Reactivity and Reactions of Acyl Chlorides
RCCl
O
+ R'COH
O
RCOCR'
O O
+ HCl
Acyl chlorides react with carboxylic acids to give
acid anhydrides:
via: CR
O
Cl
OCR'
HO
Reactions of Acyl Chlorides
Reactions of Acyl Chlorides - Example
H3C
Cl
O
H3C
OH
O
H3C
O
O
CH3
O
N
pyridine - solvent
(78-83%)
RCCl
O
+ RCOR'
O
+ HCl
Acyl chlorides react with alcohols to give esters:
R'OH
via: CR
O
Cl
OR'
H
Reactions of Acyl Chlorides with Alcohols
via: CR
O
Cl
OCR'
H
O
Reactions of Acyl Chlorides
via: CR
O
Cl
OR'
H
via: CR
O
Cl
NR'2
H
Acylation with Alcohols
N
pyridine - solvent
(80%)
Cl
O
H3C
CH3H3C
OH
O
O
CH3
CH3
CH3
RCCl
O
+ RCNR'2
O
+ H2O
Acyl chlorides react with ammonia and amines
to give amides:
R'2NH + HO–
+ Cl–
via: CR
O
Cl
NR'2
H
Acylation with Amines
Acylation with Amines - Example
N
pyridine - solvent
(90%)
Cl
O
N
O
NH