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CARBOXYLIC ACIDS
INTRODUCTION
Decarboxylation is a chemical reaction that releases CO2. Usually,
decarboxylation refers to a reaction of carboxylic acids, removing a
carbon atom from a carbon chain. The reverse process, which is the first
chemical step in photosynthesis, is called carbonation, the addition of
CO2 to a compound.
Useful in Synthetic and Bio-Organic Chemistry.
Note also that the nucleophile in an SN1 reaction does not have to bear a
negative charge. In fact, these reactions are typically performed under
"solvolysis" conditions, i.e., simply heating the starting material in a protic
solvent (an alcohol or carboxylic acid) that can also act as a nucleophile. In
these cases, of course, the product of carbocation capture by the solvent
will bear a "+" charge, and it will have to lose H+ in order to form a neutral
product. Similarly, the base in an E1 reaction does not have to be strong.
In fact, the base must not be strong, otherwise the E2 mechanism will be
followed. It is common for the solvent to act as the base in an E1 reaction,
just as it acted as the nucleophile in an SN1 process
Self-test question #1
The following products are formed when tert-butyl
bromide is heated in ethanol:
solvents
Correlation of Structure and Reactivity for Substitution and Elimination Reactions
Hali
de SN1 SN2 E1 E2
Type
Occurs
RCH2 Does not Highly Does not when
X occur favored occur strong
(primary)
bases
are used
Can Can
Occurs
occur occur Favored
in
R2CH with with when
competiti
X benzylic benzylic strong
on
(secondary)
and and bases
with E2
allylic allylic are used
reaction
halides halides
Occurs
Favored Favored
in
in Does not when
R3CX competiti
hydroxyli occur bases
(tertiary)
on
c are
with SN2
solvents used
reaction
Self-test question #5
Although it is difficult for most beginning students to predict which of the four
modes of reactivity -- SN1, SN2, E1, and/or E2 -- will be followed for a
particular set of conditions, one should certainly be able to say which mode
of reactivity was followed if shown the reactants, conditions, and products of a
particular reaction. For each of the products of the reactions shown below,
indicate which of the four mechanisms was involved in its formation. Use the
"structure/reactivity correlation chart"shown above if you need help:
FriedelCrafts alkylation involves the alkylation of
an aromatic ring with an alkyl halide using a
strong Lewis acid catalyst. With anhydrous ferric
chloride as a catalyst, the alkyl group attaches at
the former site of the chloride ion.
FriedelCrafts alkylation is a reversible reaction
This reaction has one big disadvantage, namely that
the product is more electrophilic than the reactant due
to the electron donating alkyl-chain.
Steric hindrance can be exploited to limit the number of
alkylations, as in the t-butylation of 1,4-dimethoxybenzene
Alkylations are not limited to alkyl halides:
FriedelCrafts reactions are possible with
any carbocationic intermediate such as
those derived from alkenes and a protic
acid, Lewis acid, enones, and epoxides.
It is a REDUCTION reaction
Reaction
Mechanism
PBr3 replaces the carboxylic OH with a bromide, resulting in a carboxylic acid
bromide. The acyl bromide can then tautomerize to an enol, which will readily
react with the Br2 to brominate a second time at the position.
In neutral to slightly acidic aqueous solution, hydrolysis of the -bromo acyl
bromide occurs spontaneously, yielding the -bromo carboxylic acid in an example
of a nucleophilic acyl substitution. If an aqueous solution is desirable, a full molar
equivalent of PBr3 must be used as the catalytic chain is disrupted.
If little nucleophilic solvent is present, reaction of the -bromo acyl bromide with
the carboxylic acid yields the -bromo carboxylic acid product and regenerates the
acyl bromide intermediate. In practice a molar equivalent of PBr3 is often used
anyway to overcome the slow reaction kinetics.
The mechanism for the exchange between an alkanoyl bromide and a carboxylic
acid is at below. The -bromoalkanoyl bromide has a strongly electrophilic
carbonyl carbon because of the electron-withdrawing effects of the two bromides.
The carboxylic acid will act as a nucleophile that the carbonyl oxygen of the
carboxylic acid has a partial negative charge
.
Mechanism *(continued)
Function of Reagent
Another use for PBr3 is as a catalyst for the -
bromination of carboxylic acids. Although acyl
bromides are rarely made in comparison
with acyl chlorides, they are used as
intermediates in Hell-Volhard-Zelinsky
halogenation.[4] Initially PBr3 reacts with the
carboxylic acid to form the acyl bromide,
which is more reactive towards bromination.
Function of Reagent
overall process can be represented as
Extra Info
Unlike other halogenation reactions, this
reaction takes place in the absence of a
halogen carrier. The reaction is initiated by
addition of a catalytic amount of PBr3, after
which one molar equivalent of Br2 is added.
It is a nucleophilic substitution reaction.
Examples
Hoffman maritus rearrangement
The HofmannMartius
rearrangement in organic chemistry is
a rearrangement reaction converting an
N-alkylated aniline to the
corresponding ortho and / or paraaryl-
alkylated aniline. The reaction requires
heat and the catalyst is an acid
like hydrochloric acid [1][2]
The reaction is also known to work
for aryl ethers and two
conceptually related reactions are
the Fries rearrangement and
the FischerHepp rearrangement.
Itsreaction mechanism centers
around dissociation of the reactant
with the positively charged organic
residue R attacking the aniline ring
in a FriedelCrafts alkylation.
In one study this rearrangement is
applied to a 3-N(CH3)(C6H5)-2-
oxindole
HOFFMANN BROMAMIDE
DEGRADATION
Preliminary information
Ans: a
Ans: b,c
Variation
Several reagents can substitute for bromine. N-
Bromosuccinimide and 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) can effect a Hofmann rearrangement. In the following
example, the intermediate isocyanate is trapped by methanol,
forming a carbamate.[4]
HOFMANNS
ELIMINATION REACTION
THE MECHANISM
THE DEFINITION
When a quaternary salt obtained by the
exhaustive methylation of an amine is treated
with moist silver oxide, corresponding
quaternary hydroxide is obtained which, on
heating at 400K, undergoes an elimination
reaction to yield an alkene, trimethylamine
and water. This reaction is called Hofmanns
Elimination Reaction
Simplifying the definition
Quaternary means a group of four. In this
case, four alkyl groups surrounding one
nitrogen atom denotes the quaternary salt.
So, simply put, this reaction deals with a salt
derived from an amine.
It is treated with moist silver oxide, forming a
hydroxide.
Finally, due to heating, it loses a water molecule
to produce an alkene and a trimethylamine.
Hoffmans Rule
It states that the loss of the -hydrogen occurs preferably from the
most unhindered position in the quaternary hydroxide. The
product alkene with fewer substituents will predominate.
This rule is followed in the reaction while determining the major
product.
C-2 from the right is the lesser substituted carbon. Hence elimination occurs there and
The corresponding alkene is formed. Steric hindrance of C-4 inhibits elimination.
THE MECHANISM
THE MAJOR PRODUCT
According to Hofmanns
rule, these are the major
compound. Unlikely compounds
Hell-Volhard Zelinsky
Reaction
In this reaction the alpha-H is replaced by a halogen atom on
reaction of the carboxylic group with red phosphorus and Cl2 or
Br2
Br
Br2,red P Br2,red P
RCH2COOH RCHCOOH RCCOOH
Br
Br
Unlike any other halogenation, this reaction takes place in the
absence of a halogen carrier. PBr3 replaces the carboxylic OH
with a bromide,resulting in a carboxylic acid bromide. The acyl
bromide then tautomerises to form an enol which readily
reacts with Br2 to brominate a second time at the alpha
position. tautomerises
PBr3
RCH2COOH RCHCOOH RCH=CBr
Br OH
-HBr
+
RCHCOBr Br2
Br
SN1 reaction takes place between carboxylic acid bromide and
carboxylic acid to yield alpha bromo carboxylic acid and acyl bromide
intermediate. The alpha bromoalkanoylbromide acts as a strong
electrophile due to the -I effect of the two bromide groups. While the
carbonyl oxygen of the carboxylic acid acts as a neuclophile due to its
lone pair.
R =O .. Br R
R
Br RCH2COOH
Br O-
+
= O+ Br
Br
RCHCOOH Br R
OH
+ R Br R
RCH2C=O
=O
R O =O
Br H =O+
O Br-
Hydroboration
Oxidation
What Is It?