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Unless otherwise stated, all images in this file have been reproduced from:
Blackman, Bottle, Schmid, Mocerino and Wille, Chemistry, 2007 (John Wiley)
ISBN: 9 78047081 0866
Chem 1002 Week 7 notes
FLASHBACK
Carboxylic Acids
This functional group has different properties to eitherthe carbonyl (C=O) group or the alcohol group (OH).
Must consider the functional group ‘COOH’ as a whole.
O
C
R OR = alkyl, aryl, H
All of this is the functional group
H
Carboxylic Acid DerivativesStructure
• Carboxylic acid derivatives all have an acylgroup, attached to a heteroatom (O, N, halogen)that is an element of the periodic table groups15,16, or 17
• Four classes to consider here:
RC
Cl
O
acid chloride
RC
O
O
R'
ester
RC
N
O
R'
R"
amide
RC
O
O
CR
O
acid anhydride
O
C
R Y
acyl
-OH of carboxylic acid replaced by new group
HydrolysisAll carboxylic acid derivatives can be hydrolysed to the parent
acid and another product with water
RC
Cl
O
acid chloride
RC
O
O
ester
RC
N
O
R'
R"
amide
+ H2O + H2O + H2O
RC
OH
O
+
H Cl
R'
RC
OH
O
OR'H
RC
OH
O
N
R'
R"H+ +
hydrochloric acid alcohol amine
acid acid acid
RC
O
O
acid anhydride
+ H2O
C
RC
OH
O
H
+
acid
acid
R
O
OC
R
O
Hydrolysis
Rate of hydrolysis depends on reactivity of derivative Acid chlorides and anhydrides hydrolyse in water at pH 7 Esters require H+ or OH- catalyst and heat to hydrolyse Amides require conc H+ or OH- and prolonged heating
RC
Cl
O
acid chloride
RC
O
O
ester
RC
N
O
R'
R"
amide
R'
most
reactive
least
reactive
increasing reactivity
RC
O
O
CR
O
acid anhydride
HydrolysisEnsure that products that are capable of ionization or protonation
are given in their correct ionic or molecular state
The rate of hydrolysis depends on the reactivity of the derivative
! A cid chlorides and anhydrides hydrolyse in water at pH 7
! E s ters require H+ or OH
- catalyst and heat to hydrolyse
! A mides require conc H+ or OH
- and prolonged heating
RC
Cl
O
acid chloride
RC
O
O
ester
R'
RC
N
O
R'
R"
amide
Derivative Relative Reactivity
Conditions of Hydrolysis
Products of Acid Hydrolysis
Products of Base Hydrolysis
low
high
incre
as
ing
reac
ti vity
H2O
H / H2O / heat
OH / H2O / heat
H / H2O / heat
OH / H2O / heat
RC
OH
O
RC
O
O
RC
OH
O
+ R'OHR
CO
O
+ R'OH
RC
OH
O
+R
CO
O+ R'R"NH
R"
NR' H
H
ClCl
Hydrolysis
RC
Cl
O
acid chloride(electrophile)
+O
H H
!
!
water(nucleophile)
step 1
RC
Cl
O
O
H
H!!
!
nucleophilic
addition!
Mechanism: Nucleophilic acyl substitution
step 1: nucleophilic addition to electrophilic carbon of acid chloride ... gives a tetrahedral intermediate
step 2: acid/base reaction (deprotonation of the tetrahedral intermediate)
step 3: collapse of the
tetrahedral intermediate
to regenerate the C=O
!-bond with elimination
of chloride anion as
leaving group
step 2acid-base
reaction
RC
Cl
O
O
H
+ H
Base
RC
O
O
+
H
hydrochloric acidcarboxylic acid
Cl
step 3H
elimination
Hydrolysis of EstersNote that the products formed depend on the conditions used
eg., Aspirin
+
OH
O
O
OH3C
cold 1M HClno reaction
boiling 3 M HCl
3 hours
OH
O
O
H
OH
O
H3C
cold 1M NaOH O
O
O
OH3C
Na
boiling 4 M NaOH
3 hours +OH
O
O
O
O
H3C
Na
Na
Hydrolysis of AmidesNote that the products formed depend on the conditions used
eg.
H2NNH
O
cold 1M HCl
no reaction
boiling 4 M HCl
12 hours
cold 1M NaOH
boiling 6 M NaOH
12 hours +H2N
ON
H H
O Na
NNH
O
H
HH
Cl
NOH
O
H
HH
Cl
+
N
H H
H
Cl
Exercise
Suggest reagents for the following reactions
O
NH2
O
OH
+ NH4
O
O
+ NH3
heat
H2O / H
heat
H2O / OHOH
Interconversion
A more reactive carboxylic acid derivative can beconverted into a less reaction one Involves substituting heteroatom part attached to acyl group
for a new group
Reaction mechanism is nucleophilic acyl substitution Mechanism is essentially the same for all conversions
RC
Cl
O
acid chloride
RC
O
O
ester
RC
N
O
R'
R"
amide
R'
most
reactive
least
reactive
increasing reactivity
RC
O
O
CR
O
acid anhydride
Interconversion - summary
R OH
O
SOCl2R'OHH+ (cat)
carboxylic acid
ester
acid chloride
R Cl
O
R OR'
OR'OH
R NHR'
O
amide
R'NH2 excess
R'NH2
H+ (cat)
heat
heat
most reactive
least reactive
Interconversion - examples
Acid chloride to ester
H3CC
Cl
O
RC
N
O
H
CH3+N
H
CH3H
+ H Cl
2 equivalentsneeded
reacts with amine!
N
H
CH3H
N
H
CH3H
HCl
H3C
C
Cl
O
R
C
O
O
CH3+
O
CH3H+ H Cl
Acid chloride to amide
Interconversion - examples
Ester to amide (fairly difficult to achieve)
OCH3
O
NCH2CH3
O
+ HOCH3H NCH2CH3+
ester + amine = amide + alcohol
H
H
heat
Development of aspirin
OH
O
OH
Salicylic acid1860
AntipyreticAnalgesic
But sour and irritating
Sodium salicylateStill an irritant
ONa
O
OH
O
O
OH Phenyl salicylate1886
“Salol”Phenol biproduct
OH
O
O
O
Acetylsalicylic acid1897 Bayer: “aspirin”
Sodium salt is “aspro clear”
O
O
OH
Methyl salicylateRub-on analgesic
“oil of wintergreen”
Interconversion - examples
Acid anhydride to ester
OH
O
O
OH3C
OH
O
OH
+
H3C O CH3
O O heat
+ HO CH3
O
acetic anhydride acetic acid
ester
Aspirin synthesis involves this reaction. The reagent acetic anhydride is anillegal compound in Thailand because it can be used in heroin production.
Exercise
Suggest reagents …
H3C C
Cl
O
H3C C
OCH(CH3)2
O
H3C C
OH
O
H3C C
NHCH3
O
H3C C
O
O
Interconversion of Carboxylic Acid Derivatives
CH3CH2 C
Cl
O
+ HOCH3
COOH
COOCH3
+ OH
+ OH
OH
O
+ SOCl2
Question: Draw all the products from the following reactions:
Recap
Ester & amide formation
Cl
O
OCH2CH3
O
+ HClH OCH2CH3+
acid chloride + alcohol = ester + HCl
OCH3
O
NCH2CH3
O
+ HOCH3H NCH2CH3+
ester + amine = amide + alcohol
H
H
Cl
O
NCH2CH3
O
+ HClH NCH2CH3+
acid chloride + amine = amide + HCl
H
Hneed to add a base to scavenge HCl or it will react with starting amine
heat
Di-Esters
+ H OCH2CH3
Cl
O
Cl
O2
OCH2CH3
O
H3CH2CO
O+ 2 HCl
diacid chloride + alcohol = diester + HCl
Cl
O
H OCH2CH2O H
OCH2CH2O
O O
+2
+ 2 HClacid chloride + dialcohol = diester + HCl
Di-amides can be made similarly, using amines in place of the alcohols
Di-Amides
+
H
NCH2CH3
Cl
O
Cl
O2
N
O
N
O + 2 HCl
diacid chloride + amine = diamide + HCl
H
H H
Cl
OH
NH
N
O
O
+
2
+ 2 HCl
acid chloride + diamine = diamide + HCl
HN
H
N
H
H
Polymer formation - polyesters+
Cl
O
Cl
O
OCH2CH2O
O
Cl
O + HClH OCH2CH2O H
di(acid chloride) + dialcohol = polyester + n HCl
H
OCH2CH2O
O
Cl
O
OCH2CH2O
OO
H
+ HCl
OCH2CH2O
O
Cl
O
OCH2CH2O
OO
OCH2CH2O
OO
H
+ HCl
OCH2CH2O
O
OH2CH2CO
O
OCH2CH2O
OO
OCH2CH2O
OO
H
OCH2CH2O
OO
n
O
Cl
O+ HCl
Condensation Polymers
This type of polymerisation usually involves ejection ofa small stable molecule, eg HCl, CH3OH, H2O
If polymerisation conducted above b.p. of ejected molecule,this is ‘lost’ as gas, so doesn’t interfere with polymer product
condensation reaction
O
O
N
H
H
N
Cl
O
Cl
O
NN
+ H Cl
H
H
H
H
n
nnylon
Structure of Nylon
Regular packing and hydrogen bonding gives strengthwhile retaining flexibility
N
H
O
O
N N
HH
O
N
H
O
O
N
H
N
H
O
O
N N
HH
O
N
H
O
O
N
H
! !!
!!
!!
!!
!
nylon 6,6 space filling model …
Strength & Structure
eg., Lycra Rigid groups give a fabric strength Hydrocarbon chains provide elasticity (remember conformers)
O
H2C C
H2
OC
O
N
H
CH2 N
H
O
N
H
N
H
O
N
H
N
H
O
nm
Elastic segment Rigid segment
Molecular structure links directly to macroscopic properties
Kevlar
Kevlar is used in bullet proof vests. What feature of themolecular structure makes it suitable for this application?
Rigid aromatic rings and hydrogenbonds between the polymer chains
Exercise
Suggest reagents for the following conversions …
OH
HO
O
O OCH3
H3CO
Ester - suggests made from carboxylic acid
Got to be oxidised atthese positions
Answer to Exercise
O
O Cl
Cl
1. K2Cr2O7/ H+
Suggest reagents for the following conversions …
OH
HO
O
O OCH3
H3CO
2. SOCl2
3. CH3OH
O
O OH
HO
No directroute
Synthesis & Retrosynthesis
OBr
convert into
Necessary to replace bromine by an oxygen and to oxidise sp3 centre to sp2
Synthesis & Retrosynthesis
Combine the two to solve our puzzle …
First step
Nucleophilic Substitution
Use H2O (and dilute OH-)
OH OBr
Second step
Oxidation
Use K2Cr2O7 and H+
Exercise from 2008 exam paper
Show clearly the reagents you would use to carry out the following chemical conversion.Two steps are required. Give the structure of the intermediate compound.
How could you distinguish between the starting material and the product by 13C NMRspectroscopy?
Br
Br
no direct method
Formidable achievements!
Brevotoxin B
TaxolO
O
OH
HN
PhO
AcO OOBz
O
HOH
OAcO
O
…
Both of these havebeen synthesized in the
laboratory byorganic chemists
Organic Chemistry Summary
Remember: Carbon as a stable neutral organic compound always has 4 bonds to it as a result of it's tetravalency. (Nitrogen has 3 bonds, one lone pair; Oxygen has 2 bonds, 2 lone pairs; Chlorine, bromine, iodine have one bond, 3 lone pairs)
Draw and/or recognise organic line structures and interconvert to structural and molecular formulae
Recognise the functional groups present in a molecule and name molecules
Recognise and differentiate between different types of isomers
Determine information about structure from spectroscopic data
Recognise what type of a reaction is occurring (substitution, elimination, acid-base, addition, oxidation, reduction) and give the expected products from these reactions and/or the reagents required for a given reaction.
What you should be able to do:
Organic Chemistry Summary
Electrophile: A species that seeks an electron pair
Nucleophile: A species that supplies an electron pair
Very important definitions - remember an electrophile will always react with a nucleophile.
The nucleophile provides a pair of electrons that become a bond between the two species
ENu ENu+
Nucleophile - a species that provides an electron pair
Electrophile - a species that seeks an electron pair
Reaction Summary
ACID-BASE ADDITION ELIMINATION SUBSTITUTION REDOX
1. 2. 3. 4. 5.
• electrophilic • nucleophilic • oxidation• reduction
1. Acid - Base reactions
Organic molecules containing O-H bonds can act as acids (proton donors)
Organic molecules containing amines can act as bases (proton acceptors)
Alcohols
Phenols
Carboxylic acids
(Amines can be primary, secondary, tertiary or aryl)
Reaction Summary
1. Acid - Base reactions (cont.)
NaNH2
NaOH
NaHCO3
Alcohol Phenol Carboxylic Acids
OH
O
ROH RCO2H
RO RCO2
x
x x
! !
!
!
!
!
Acids
Conjugate bases
Incre
asin
g b
ase
str
ength
Increasing acid strength
Reaction Summary
1. Acid - Base reactions (cont.)
amine
H
OH
N
R'R''R'''
N
R'R''R'''
Hbase
(soluble in aqueous acid)
Reaction Summary
2. Addition reactions
C CH
H
H
H C CH
H
H
H
XXX2
CCl4 solvent
(X = Br, Cl)Halogenation
C CH
H
H
H C CH
H
H
H
HH
Pd catalyst
H2Hydrogenation
Electrophilic addition to alkenes (alkene !-bond electrons are accessible to electrophiles)
Reaction can occur with H2, X2, HX and H2O (where X = Cl, Br)
Reaction Summary
2. Addition reactions (cont.)
C CCH3
H
H
HC C
CH3
H
H
H
HX
C CCH3
H
H
HC C
CH3
H
H
H
HOHH2SO4
X = Cl, Br, I
dilute
CCl4 solventHydrohalogenation
Hydration
HX
For unsymmetrical alkenes and unsymmetrical reagents remember MARKOVNIKOV'S RULE
The H from the unsymmetrical reagent goes to the C of the C=C bond that already has the most H's directly attached
Reaction Summary
3. Elimination reactions
hot conc
Remember Zaitsev's rule: If there is a choice, the more substituted alkene will be formed
Alcohols
H2SO4
Alkyl halides
OH
X hot conc OHethanol solvent
Reaction Summary
4. Substitution reactions
R X R Nu
Nucleophilic Substitution
+ Nu + X
X = Cl, Br, I
Alkyl Halides
Nu = HO R-O NH2CN RC C
This is a good method for forming quaternary ammonium salts:
H3C N
CH3
CH3
CH3 IN
CH3
CH3
H3C IH3C
Reaction Summary
4. Substitution reactions (cont.)
Nucleophilic Acyl Substitution
ACID DERIVATIVES: Hydrolysis and Interconversion
General reaction:
RC
Y
O
RC
Z
O
ZH H Y+ +
more reactive derivative
less reactive derivative
Note: can directly convert a more reactive derivative into a less reactive derivative.
RC
Cl
O
RC
O
O
RC
N
O
R'
R"R'R
CO
O
CR
Oacid chloride ester amide
most
reactive
least
reactive
increasing reactivity
acid anhydride
Reaction Summary
4. Substitution reactions (cont.)
R C
O
OH R C
O
Cl
Interconversions
Acid Chlorides
RC
O
Cl OH RC
O
OR'
RC
O
Cl NH
R'
R''R
C
O
NR'
R''
R'
ester
+ HCl
amide
+ HCl
SOCl2
Reaction Summary
4. Substitution reactions (cont.)
Acid Anhydrides
RC
O
OC
O
R RC
O
OR'
HOC
OROH
RC
O
OC
O
RNH
R'
R''R
C
O
NR'
R''
R'
HOC
OR
ester
+
+
amide
RC
O
OR' NH
R''
R'''
Esters
+ R'—OHheat
RC
O
NR'
R''amide
Reaction Summary
4. Substitution reactions (cont.)
Hydrolysis
R C
O
Y
R C
O
O
R C
O
OHH /H2O
OH /H2O
+
or
or
R'OH (ester)
HCl (acid chloride)
or
R'2NH2
R-CO2H (acid anhydride)
acid derivative (amide)
+
or
or
R'OH (ester)
Cl (acid chloride)
or
R'2NH2
R-CO2 (acid anhydride)
(amide)
Reaction Summary
5. Redox reactions
R C R C
R C
OH
H
R'R
CR'
O
Cr2O72- / H+
primary alcohol
acid
Cr2O72- / H+1. NaBH4 or LiAlH4
2. H+/H2Oaldehyde
secondary alcohol
ketone
Cr2O72- / H+
1. LiAlH4 2. H+/H2O
or NaBH4
oxidation
oxidation
reduction
reduction
1. LiAlH4
2. H+/H2O
reduction
oxidation
O
H
O
OHR-CH2OH