Download carboxylic acid

Carboxylic acids and carboxylic acid derivatives
Carboxylic acid
The carboxyl group is the first complex functional group. It consists a C=O and OH, but due
to their interactions it is not an oxo compound and not an alcohol.
Carboxylic acids, compounds of the type
Classification
● According to R group
- unsubstituted / substituted
- saturated / unsaturated / aromatic
- linear / branched / cyclic
Within the substituted carboxylic acids: halogen, hydroxy, oxo and amino acids (the
most important)
Other subgroups: 2- (-), 3- (β-), 4- (γ-), …
● According to the number of carboxyl groups mono-, di-, tri-, ..., polycarboxylic acids
Carboxylic Acid Derivatives
Summarized as follows: one oxygen atom substitution with other hetero atoms - visibly a
lot of variations is possible!
The most important ones are:
Nomenclature of Carboxylic Acids and their Derivatives
1. Carboxylic Acids
Nowhere in organic chemistry are common names used more often than with the carboxylic
acids.
 monocarboxylic acids: C1 = formic acid (acidum formicum), C2 = acetic acid (acidum
aceticum), …, C4 = butyric acid (acidum butiricum), …
 dicarboxylic acids: C2 = oxalic acid (acidum oxalicum), C3 = malonic acid (acidum
malonicum), C6 = glutaric acid (acidum glutaricum), …
 substituted carboxylic acids– natural sources: hydroxy carboxylic acids
Systematic names: Substitutive nomenclature
 acyclic compounds - The name of the corresponding hydrocarbon base + „oic acid”
ending (alkanoic acid) --- In case of dicarboxylic acid "diacid" ending–
Systematic names for carboxylic acids are derived by counting the number of carbons in the
longest continuous chain that includes the carboxyl group and replacing the -e ending of the
corresponding alkane by -oic acid. The first three acids. When substituents are present, their
locations are identified by number; numbering of the carbon chain always begins at the
carboxyl group.
If there is a higher priority group / skeleton  COOH prefix („carboxy”)
Notice that compounds containing OH group are named as hydroxy derivatives of
carboxylic acids, rather than as carboxyl derivatives of alcohols. We have seen earlier that
hydroxyl groups take precedence over double bonds, and double bonds take precedence
over halogens and alkyl groups, in naming compounds. Carboxylic acids outrank all the
common groups we have encountered to this point.
Double bonds in the main chain are signaled by the ending -enoic acid, and their
position is designated by a numerical prefix.
 cyclic carboxylic acids or polycarboxylic acids (n ≥ 2)  „ carboxylic acid” suffix
connected to main hydrocarbon chain - In this case the group COOH is not numbered!
When a carboxyl group is attached to a ring, the parent ring is named (retaining the final -e)
and the suffix -carboxylic acid is added.
Compounds with two carboxyl groups are distinguished by the suffix -dioic acid or dicarboxylic acid as appropriate. The final –e in the base name of the alkane is retained.
Nomenclature of Carboxylic Acid Derivatives
In naming carboxylic acid anhydrides in which both acyl groups are the same, we
simply specify the acyl group and add the word “anhydride.” When the acyl groups are
different, they are cited in alphabetical order.
Substitutive IUPAC names for nitriles add the suffix -nitrile to the name of the parent hydrocarbon
chain that includes the carbon of the cyano group. Nitriles may also be named by replacing the -ic acid
or -oic acid ending of the corresponding carboxylic acid with -onitrile. Alternatively, they are
sometimes given functional class IUPAC names as alkyl cyanides.
2. Group names derived from carboxylic acids
Usual name: acyl
Trivial name: „Latin base" + "YL" suffix
In case of systematic name: name– ”acid” + „oil” – functional group name does NOT
exist!!
Name of polyacids / cyclic acid– „ carboxylic acid” suffix+ carbonyl ending
3. Carboxylic acid salts / carboxylate ions
- Trivial name: „Latin base" + „ate" suffix
- systematic name: - „acid” ending+ „oate” suffix
- In case of a cyclic systems : - „carboxylic acid” suffix+ „ carboxylate”
4. Carboxylic acid halides
- Trivial name: „Latin base" + "YL" suffix
- systematic name: - ”acid” + „oil” suffix
- cyclic systems:
„carboxylic acid” suffix +„carbonyl halogenide”
O
Prefix: „halogen formyl” (eg. bromoformyl)
Br
+ Beginning
with the cation
name!!
5. Carboxylic acid anhydrides
5.1. The simplest case: symmetric unsubstituted anhydrides
any type of nomenclature: „anhydride” suffix (propionic anhydride,
heptanoic anhydride, cyclopentane carboxylic acid anhydride)
5.2. Symmetric unsubstituted anhydrides
bis(X-carboxylic acid)anhydride
bis(chloro acetic acid) anhidrid
5.3. Mixed acid anhydrides: name of component acids in alfabetic order +
„anhydride” ending. Pl. acetic formic anhydride
6. Carboxylic acid esters
6.1. Traditional names= „salt like”, formaly carboxylate
6.2. Ester of the given carboxylic acid
6.3. Higher priority group in the chain
acyloxy (RCOO-) or alkoxy/aryloxy carbonyl (ROCO-) prefix
7. Carboxylic acid amides
7.1. primary amides
- In case of trivial name: „latin base” + „amide” suffix
- In case of systematic name: carboxylic acid + amid suffix
- In case of cyclic systems: instead of „carboxylic acid” suffix „carboxamide”
7.2. Secondary and tertiary amides – derivatives of N-(di)substituted of primary amides
Bonding system of carboxylic acids and their derivatives
O
R
O
H
 +  model, + M effect (conjugative interaction with
nonbonding e-pair and -bond) three-center, four-electron
bond
sp2 hybridization of the hydroxyl oxygen allows one of its unshared electron pairs to be delocalized by
orbital overlap with the  system of the carbonyl group In resonance terms, this electron delocalization
is represented as:
Important consequences :
Delocalized bonding system – resonance structure!
The sp2 hybrid state and +M effect are
proved by bond angles and distances!
C(sp3)-OH bond distance~ 143 pm!!
Bond angle: steric effects
- C=O bond distance increases,
- C-O bond distance is shortened, bond
order is increases
- „ carbonyl” O high electron density
(basic/nucleophile) center
Generally:
LCAO-MO description
similarity to NO2
group!!
The effect of quality of heteroatom :Y
1. EN (Cl > O > N)
2. Ability for + M effect (it basically depends on the size, pl. Cl > Br, O > S)
The electron distribution (the share of resonance structures) the resultant of the two
factors, it is determining the stability of the carboxylic acid derivatives and reactivity.
1. example: carboxylic acid anhydride vs. carboxylic acid ester
For carboxylic anhydride
bidirectional electron shift,
smaller stabilization
2. example: carboxylic acid amides
Th electronegativity of N is small (relatively weak
–I), good donation for nonbonding e-pair on N 
C=N double bond is dominant
Stability is increasing (biological importance: peptides), high planarity, restricted
rotation around the C-N bond  existence of diastereomers
Rotation Barrier - G‡ = 63 – 84 kJ/mole!!!
Special case: carboxylate ion– fully balanced electronic structure, equivalent resonance
structures, symmetric charge distribution
stable anion
dC-O = 0.127 nm
The physical properties of carboxylic acids and their derivatives
1. Carboxylic acids
Boiling point values:
Intermolecular H-bridge,
"dimeric" structure
~ 0.10 nm
induced dipoledipole-dipole H-bond
induced dipole
Double
H-bond
PhCOOH; mp: 122 oC, bp: 250 oC
Apparently, the Mp. curve not monotonic increasing, Bp. is monotonic increasing
The water solubility of carboxylic acids: at lower number C is high, in homologous line
decreases (cf. H-bridge solvation)
2. Carboxylic acid amides
Name
Mp (°C) Bp (°C) water solubility
HCONH2
formamide
2
193
soluble
CH3CONH2
acetamide
82
222
soluble
CH3CH2CONH2
propionamide 81
213
soluble
CH3CH2CH2CONH2 butyramide
115
216
soluble
C6H5CONH2
benzamide
132
290
limited
Stronger associates than its carboxylic acids, therefore higher mp and bp.
Solubility in water at low Cn unlimited or good.
3. Carboxylic acid halides, anhydrides, esters
Mp, bp is lower than RCOOH, RCONHR1 – only dipole-dipole interaction
Bp. (oC)
Mw
AcOH
118
60.05
AcNH2
222
59.07
Ac2O
138-140
102.09
AcOMe
57-58
74.08
AcCl
52
78.50
Chemical properties of carboxylic acids and their derivatives
1. Acidity of carboxylic acids and acid derivatives
For acidic strength the stability of the resulting anion is determining 
O-H (S-H), N-H and C-H acidity
1.1. Carboxylic acids
HCOOH
CH3COOH
pKa
3.75
4.76
Due to the high stability of the carboxylate: significant acidity
C(2-5)COOH
4.81-4.88
Incorporation of an alkyl group reduces the acidity – EDG group!  decreasing anion stabilty
The effect of the substituents of alkyl group – EWG substituents increasing the stability of
the carboxylate ion  increasing acidity
Ionisation Constant
pKa
The acidic strength
increase depends on
the numbers and
position of EWG
substituents
CF3COOH – pKa = 0.23!! (acidity of inorganic acids)
EtCHClCOOH – pKa = 2.86, MeCHClCH2COOH – pKa = 4.05, Cl(CH2)3COOH – pKa = 4.76
1.1. Acidity of carboxylic acids
Dicarboxylic acids – two dissociation steps, two pKa
Here already far the second
COOH (1,4-position) and seven
membered H-bond cycle…
CH3COOH –
pKa = 4.76
Aromatic carboxylic acids - 6 system and carboxylate anion 4 system has conjugation
therefore increasing stability  stronger acid
o-/p-position EDG/EWG substituents can decreasing or increasing the acidity
- I < +M
- I, - M
- I , M effect
is negligible
1.2. Acidity of carboxylic acid amides – N-H acidity
Amides exhibit increased acidity
compared with the amines.
Additional electron withdrawing /
mezomeria stabilization functional
groups increase the acidity.
alkalisoluble
1.3. Acidity of carboxylic acid esters / carboxylic acid anhydrides – C-H acidity
Analogy: C-H acidity of aldehydes/ketones (-deprotonation)
The formed carbanion: „enolate” form is very stable
R
pKa
alkyl
24-25
H
20
COOQ
13
COQ
11
Acetoacetate--- acetylacetone
β-keto carboxylic acid esters can be deprotonated even in alkali /alcoholate solution
2. Basicity of carboxylic acids and acid derivatives
C=O: oxygen has large electron density
 Brönsted-, Lewis-acids can attack
 Acid catalysed processes, increased electrophilicity of „carbonyl” C!!
3. Nucleophilic Acyl Substitution of carboxylic acid derivatives - carboxylic acid derivatives
– Conversion of carboxylic acid derivatives into each other
electrophilic character of „carbonyl” C → nucleophilic attack
In the first step, "tetrahedral intermediate„
Its formation is analogous with the reactions of aldehydes and ketones,
BUT! X is a good LG! Possibility for the formation of C=O, and even the formation of a
stable CONu unit
Acylation of Nu unit!
G
Fundamental issue (free) enthalpy
changes in the reaction –
tetrahedral
the energy relations of products
intermediate
and starting materials
Reagents
Products
reaction coordinate
Carboxylic acid derivatives:
RCOHlg < (RCO)2O < RCOSR < RCOOR1 ~ RCOOH < RCONH2 + egyéb amidok < RCOOƟ
increasing stability!
increasing reactivity!
Mostly spontaneous reactions! In the opposite direction specific reagents / conditions
Substitution reactions of carboxylic acid chlorides (halides)
Similar reactions in the
case of acid
anhydrides, although
slower reaction!
(worse leaving group)
The most important reactions of esters
starting
material of
heterocycles
irreversible (cf.
stability of
carboxylate!)
The reactivity of esters can be increased if Q containing EWG group ("active esters")
Reactions of carboxylic acids
The similar stability of carboxylic acid and ester a reversible
process - an acid catalysed reaction!!! (three different
mechanisms)
Q: reaction of carboxylic acids with nucleophiles??
Nu is a base it reacts with the acid
(deprotonation!) – carboxylate ion is very
stable – no further reaction with the Nu
1. Salt formation
2. Heating of solid
ammonium salts primary
amides can be obtained.
Rather an industrial method!
Reactions of carboxylic acid derivatives with C nucleophiles
Special case - usually irreversible process. Conditions:
● no acidic H (O-H, N-H, S-H)
● sufficiently electrophilic C=O carbon
 Derivatives that may be relevant : acid halides, acid anhydrides, esters!
1. Reaction with Grignard reagent (you know these )
Using less reactive organometallic reagent (R2Cd)
ketones can be prepared selectively.
2. Reactions with other C-nucleophiles
(Z1, Z2 at least one is EWG)
– both nucleophilic and electrophilic is derived
from the same compound (analogy to the aldol dimerization)
secondary
reactions:
ketone will
react further
It is a "crossed Claisen" version, four
products can be formed
BUT! If only one can be electrophile
than two products will be formed.
Reactions in -position
1. -Halogenation
Halogenation only in -position!
Significance: easy nucleophilic
substitution (Nu = NH2, OH, CN, …)
Different mechanisms depending on the quality of the halogen. -Bromination – via enol;
Br2/PBr3/D = Hell-Volhard-Zelinsky Reaction
2. -Oxidation
In biological
systems it is
important (Krebs
cycle, glycolysis)
R = Me (pyruvic
acid, pyruvic acid)
Oxidation and reduction of carboxylic acids and their derivatives
The carboxylic acids are the highest oxidation state of the organic compounds, oxidative
conversion of COX functional groups is not significant
Due to the high stability of the COX group the reduction is difficult!
Eg. Catalytic reduction is possible only in special cases, at high pressure and temperature.
In practice: metal hydrides
Similar reaction: RCOCl
Thermal reactions of carboxylic acids The driving force is the high stability of CO2.
Decarboxylation of alkane acid is less effective, requires
high temperatures (melt).
Easier from salts (eg. On the presence of solid NaOH).
Aromatic carboxylic acids can loose CO2 easier.
Dicarboxylic acids and β-oxocarboxylic acids can be
decarboxylated already under 100 °C
For produce simple alkanoic acid anhydride it is
not a general reaction.
For ,-dicarboxylic acids cyclic anhydrides can
be formed, preferred formation process in case of
5- and 6-membered rings
Preparation of carboxylic acids and their derivatives
1. Carboxylic acids
Due the high oxidation state of the carboxylic acids predominantly oxidative processes
Carboxylic acid mixture is formed.
Low practical significance.
Exception: symmetrical compounds (R = R1 or ring)
Practical significance: adipic acid synthesis - Nylon 66 starting
materials, E355 (flavour and gelling compound)
2.5 Mt/year!
1.1.2. Oxidation of aromatic compounds with alkyl side chain
Any R results benzoic acid derivative !
Oxidising agents: KMnO4 or K2Cr2O7/H
1.1.3. Oxidation of alcohols – mainly, primary alcohols
For secondary and tertiary alcohols: mixture!!
1.1.4. Oxidation of aldehydes – takes place easily with mild oxidizing agents
Aldehyde synthesis: particularly from 1o alcohols
1.2. Substitution methods (C1 fragment incorporation)
1.3. Aromatic carboxylic acids – Kolbe and Kolbe-Schmidt-synthesis
1.4. ,β-unsaturated carboxylic acids – Perkin-, Knoevenagel-syntheses
2. Carboxylic acid derivatives
Basically from carboxylic acid derivative with interconversion – from the more reactive
derivative a more stable product can be easily obtained
Q: Preparation of a highly reactive, unstable derivatives from carboxylic acids
Reagents: SOCl2, SO2Cl2, PCl3, POCl3, PCl5, …
Thermal activation + highly reactive reaction partner (inorganic acid chloride!!) +
LeChatelier-Braun principle  synthetically used reaction
Preparation of carboxylic acid anhydrides
eg. P2O5