chem1002 – organic chemistry · chem1002 – organic chemistry 1. representations of molecular...
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CHEM1002 – Organic Chemistry
1. Representations of Molecular Structure
2. Alkanes, Alkenes, Alkynes
3. Aromatic Compounds
4. Structure Determination
5. Alcohols & Amines
6. Stereochemistry
7. Organic Halogen Compounds
8. Aldehydes & Ketones
9. Carboxylic Acids & Derivatives
10. Synthetic Strategies
OH
O
O
OH3C
Aspirin
Reactions: Substitution Substitution of the OH group
Thionyl chloride reacts to form an acid chloride
H3CC
O
O+
ClS
Cl
O
H3CC
Cl
O+ Cl +
acetic acid(ethanoic acid)
acetyl chloride(ethanoyl chlor ide)
S
O
O
sulfur dioxide
HH
Carboxylic Acids - Reactions
OH
OOH 1) LiAlH4
2) H+
SOCl2
Draw the products of the following reactions:
O
O
Cl
O
OH
CO2-
Carboxylic Acids - Reactions
Give the reagents required for the following reactions:
H
O
OH
O
OH
Cl
O
O
O
Na2Cr2O7 / H+
1. LiAlH4 2. H+
OH-
SOCl2
Reactions: Ester formation
OH
O
OCH3
O
CH3OH
H+ (cat)
carboxylic acid ester
R OH
O
R OR'
OH+ (cat)+ R'OH
alcohol
heat
water+ +
It’s all in the smell!
Small carboxylic acids have an unpleasant, sour smell. In contrast esters tend to have sweet smells.
Ester Formula Flavour/fragrance
Methyl butyrate CH3CH2CH2COOCH3 Apple
Ethyl butyrate CH3CH2CH2COOCH2CH3 Pineapple
Propyl acetate CH3COOCH2CH2CH3 Pear
Pentyl acetate CH3COOCH2CH2CH2CH2CH3 Banana
Pentyl butyrate CH3(CH2)2COOCH2(CH2)3CH3 Apricot
Octyl acetate CH3COOCH2(CH2)6CH3 Orange
Methyl benzoate C6H5COOCH3 Ripe kiwi
Ethyl formate HCOOCH2CH3 Rum
Methyl salicylate HOC6H4COOCH3 Wintergreen
Benzyl acetate CH3COOCH2C6H5 jasmine
Exercise Name the functional groups.
H
O
OH
OH
O
Cl
O
O
O
Na
OCH3
O
Answers-see next page of this supplement
Exercise Suggest reagents to bring about the following reactions.
H
O
OH
OH
O
Cl
O
O
O
Na
OCH3
O
aldehyde carboxylic acid sodium carboxylate
alcohol ester acid chloride
Answers-see next page of this supplement
H
O
OH
OH
O
Cl
O
O
O
NaCr2O72- / H+ aq. NaOH
aq. HCl
1. LiAlH42. H+
1. LiAlH42. H+
SOCl2
OCH3
O
CH3OHH+ (cat)
aldehyde carboxylic acid sodium carboxylate
alcohol ester acid chloride
Answers Summary of reactions of Carboxylic Acids
FLASHBACK Carboxylic Acids
This functional group has different properties to either the carbonyl (C=O) group or the alcohol group (OH).
Must consider the functional group ‘COOH’ as a whole.
O
CR OR = alkyl, aryl, H
All of this is the functional group
H
Carboxylic Acid Derivatives Structure
• Carboxylic acid derivatives all have an acyl group, attached to a heteroatom (O, N, halogen) that is an element of the periodic table groups 15,16, 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
CR Y
acyl
-OH of carboxylic acid replaced by new group
FLASHBACK Carboxylic Acids
This functional group has different properties to either the carbonyl (C=O) group or the alcohol group (OH).
Must consider the functional group ‘COOH’ as a whole.
O
CR OR = alkyl, aryl, H
All of this is the functional group
H
Carboxylic Acid Derivatives Structure
• Carboxylic acid derivatives all have an acyl group, attached to a heteroatom (O, N, halogen) that is an element of the periodic table groups 15,16, 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
CR Y
acyl
-OH of carboxylic acid replaced by new group
Hydrolysis All carboxylic acid derivatives can be hydrolysed to the parent
acid and another product with water
RC
Cl
Oacid chloride
RC
O
Oester
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
Oacid 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
Oacid chloride
RC
O
Oester
RC
N
O
R'
R"
amide
R'
most reactive
leastreactive
increasing reactivity
RC
O
O
CR
Oacid anhydride
Hydrolysis Ensure 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
increasing rea ct i vi ty
H2O
H / H2O / heat
OH / H2O / heat
H / H2O / heat
OH / H2O / heat
RC
OH
O
RC
O
O
RC
OH
O+ R'OH
RC
O
O
+ R'OH
RC
OH
O+
RC
O
O+ R'R"NHR"
NR' HH
ClCl
Hydrolysis
RC
Cl
O
acid chloride(electrophile)
+O
H Hδ
δ
water(nucleophile)
step 1
RC
Cl
O
O
H
Hδδ
δ
nucleophilicadditionδ
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 π-bond with elimination of chloride anion as leaving group
step 2acid-base reaction
RC
Cl
O
OH
+ H
Base
RC
O
O
+
H
hydrochloric acidcarboxylic acid
Cl
step 3H
elimination
Hydrolysis of Esters Note that the products formed depend on the conditions used
eg., Aspirin
+
OH
O
O
OH3C
cold 1M HCl no 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
OO
O
H3CNa
Na
Hydrolysis of Amides Note 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
+
NH H
H
Cl
Exercise
Suggest reagents for the following reactions
O
NH2
O
OH
+ NH4
O
O
+ NH3
heatH2O / H
heat
H2O / OHOH
Interconversion
A more reactive carboxylic acid derivative can be converted 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
Oacid chloride
RC
O
Oester
RC
N
O
R'
R"
amide
R'
most reactive
leastreactive
increasing reactivity
RC
O
O
CR
Oacid anhydride
Interconversion - summary
R OH
O
SOCl2R'OHH+ (cat)
carboxylic acid
ester
acid chloride
R Cl
O
R OR'
O R'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
H Cl
H3CC
Cl
O
RC
O
O
CH3+ OCH3H + H Cl
Acid chloride to amide
Interconversion - examples
Acid anhydride to ester
OH
O
O
OH3C
OH
O
OH+
H3C O CH3
O O heat+ H
O CH3
O
acetic anhydride acetic acid
ester
Aspirin synthesis involves this reaction. The reagent acetic anhydride is an illegal compound in Thailand because it can be used in heroin production.
Exercise
Suggest reagents …
H3C CCl
O
H3C COCH(CH3)2
O
H3C COH
O
H3C CNHCH3
O
H3C CO
O
Development of aspirin
OH
O
OH
Salicylic acid 1860
Antipyretic Analgesic
But sour and irritating
Sodium salicylate Still an irritant
ONa
O
OH
O
O
OHPhenyl salicylate 1886
“Salol” Phenol biproduct
OH
O
O
O
Acetylsalicylic acid 1897 Bayer: “aspirin”
Sodium salt is “aspro clear”
O
O
OH
Methyl salicylate Rub-on analgesic
“oil of wintergreen”
FLASHBACK Fatty acids
Fatty acids are long chain carboxylic acids (C8 – C20)
Fats are esters of fatty acids and an alcohol
• Monounsaturated fatty acids contain one double bone (eg olive oil)
• Polyunsaturated fatty acids contain two or more double bonds (eg soya)
• Saturated fatty acids have alkane chain (eg coconut, animal fats, butter)
Fats
Fats are esters of long chain fatty acids and glycerol
Glycerol has three alcohol groups ⇒ forms a triester Fats are also called triglycerides Base hydrolysis of fats is used in the manufacture of soap
(e.g. sodium stearate)
H2C
HC OH
OH
H2C OH
glycerol 3 x stearic acid
saturated fat
O
O
OO
O
O
HOOC (CH2)16CH3
HOOC (CH2)16CH3
HOOC (CH2)16CH3
Intermolecular Forces • More attraction between molecules ⇒ higher melting point • ‘Attraction ‘ = intermolecular forces
• depend on functional groups present and geometry
Name No Cs Structure Mp (°C)
Lauric 12 CH3(CH2)10COOH 44
Myristic 14 CH3(CH2)12COOH 58
Palmitic 16 CH3(CH2)14COOH 63
Stearic 18 CH3(CH2)16COOH 70
Arachidic 20 CH3(CH2)18COOH 75
Palmitoleic 16 (Z)-CH3(CH2)5CH=CH(CH2)7COOH 32
Oleic 18 (Z)-CH3(CH2)7CH=CH(CH2)7COOH 16
Ricinoleic 18 (Z)-CH3(CH2)5CH(OH)CH2CH=CH(CH2)7COOH 5
Linoleic 18 (Z,Z)-CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH -5
Arachidonic 20 (all Z)-CH3(CH2)4(CH=CHCH2)4(CH2)2COOH -50
Fat versus Oil
Saturated fats (& unsaturated fats with an E double bond) pack well and tend to be solids at room temperature
Unsaturated fats with a Z double bond pack together poorly and tend to be liquid at room temperature
Saturated fatty acid
Z - unsaturated fatty acid
E - unsaturated fatty acid
Natural fats and oils
Natural lipids contain a mixture of fatty acids
Source Saturated fatty acids (%) Unsaturated fatty acids
C12 C14 C16 C18 C16 C18
Animal fat
Lard - 1 25 15 50 6
Butter 2 10 25 10 25 5
Human fat 1 3 25 8 46 10
Whale fat - 8 12 3 35 10
Vegetable oil
Coconut 50 18 8 2 6 1
Corn - 1 10 4 35 45
Olive - 1 5 5 80 7
Peanut - - 7 5 60 20
Linseed - - 5 3 20 20
Lecture Summary
You should now be able to 1. Recognise carboxylic acid derivative functional groups 2. Appreciate the different reactivity of these derivatives 3. Predict conditions for hydrolysis and interconversion of
carboxylic acid derivatives, paying particular attention that products are given in their correct ionic or molecular state.
4. Understand the physical properties of fats and oils
Next Lecture Polyesters and polyamides
Check your answers
Suggest reagents …
H3C CCl
O
H3C COCH(CH3)2
O
H3C COH
O
H3C CNHCH3
O
H3C CO
O
H2O / OH / heat
H
H2O / Hheat
SOCl2
NH2CH3
HOCH(CH3)2
Summary of Reactions of Carboxylic Acids
H
O
OH
OH
O
Cl
O
O
O
NaCr2O72- / H+ aq. NaOH
aq. HCl
1. LiAlH42. H+
1. LiAlH42. H+
SOCl2
OCH3
O
CH3OHH+ (cat)
aldehyde carboxylic acid sodium carboxylate
alcohol ester acid chloride
Interconversion - summary
R OH
O
SOCl2R'OHH+ (cat)
carboxylic acid
ester
acid chloride
R Cl
O
R OR'
O R'OH
R NHR'
O
amide
R'NH2 excess
R'NH2
H+ (cat)
heat
heat
most reactive
least reactive