Download The Functional Group Approach

Organic Chemistry – The Functional Group Approach
Br
OH
alkane
(no F.G.)
alcohol
halide
alkene
non-polar (grease, fats)
polar (water soluble)
non-polar (water insoluble)
non-polar (water insoluble)
tetrahedral
tetrahedral
tetrahedral
trigonal
O
NH
alkyne
aromatic
aldehyde/ketone
imine
non-polar (water insoluble)
non-polar (water insoluble)
polar (water soluble)
polar (water soluble)
linear
flat
trigonal
trigonal
YSU
Organic Chemistry – The Functional Group Approach
HO OH
H3CO OCH3
NH2
O
OH
hydrate
acetal
amine
carboxylic acid
polar (water soluble)
non-polar (water insoluble)
polar (water soluble)
polar (water soluble)
tetrahedral
tetrahedral
tetrahedral
trigonal
O
O
O
OCH3
O
Cl
NH2
O
O
carboxylic ester
carboxylic amide
acyl halide
acid anhydride
polar (water-solube)
polar (water soluble)
non-polar (reacts w/water)
non-polar (reacts w/water)
trigonal
trigonal
trigonal
trigonal
YSU
1
Organic Chemistry – The Functional Group Approach
Br
OH
alkane
(no F.G.)
alcohol
halide
alkene
non-polar (grease, fats)
polar (water soluble)
non-polar (water insoluble)
non-polar (water insoluble)
tetrahedral
tetrahedral
tetrahedral
trigonal
O
NH
alkyne
aromatic
aldehyde/ketone
imine
non-polar (water insoluble)
non-polar (water insoluble)
polar (water soluble)
polar (water soluble)
linear
flat
trigonal
trigonal
YSU
Organic Chemistry – The Functional Group Approach
Br
OH
alkane
(no F.G.)
alcohol
halide
alkene
non-polar (grease, fats)
polar (water soluble)
non-polar (water insoluble)
non-polar (water insoluble)
tetrahedral
tetrahedral
tetrahedral
trigonal
O
NH
alkyne
aromatic
aldehyde/ketone
imine
non-polar (water insoluble)
non-polar (water insoluble)
polar (water soluble)
polar (water soluble)
linear
flat
trigonal
trigonal
YSU
2
Carey Chapter 4 – Alcohols and Alkyl Halides
Figure 4.2 – Electron density maps of CH3OH and CH3Cl
YSU
Alcohols and Halogens in Medicine and Nature
OH OH
Cl
O2N
HN
Cl
O
Acetaminophen
Valium
Chloramphenicol
YSU
3
4.2 IUPAC Nomenclature of Alkyl Halides
• Functional class nomenclature
pentyl chloride
cyclohexyl bromide
1‐methylethyl iodide
• Substitutive nomenclature
2‐bromopentane
3‐iodopropane
2‐chloro‐5‐methylheptane
YSU
4.3 IUPAC Nomenclature for Alcohols
1‐pentanol
2‐pentanol
cyclohexanol
1‐methyl cyclohexanol
2‐propanol
5‐methyl‐2‐heptanol
YSU
4
4.4 Classes of Alcohols and Alkyl Halides
Br
Primary (1o)
Cl
OH
OH
I
Cl
Secondary (2o)
CH3
Br
Tertiary (3o)
(CH3)3COH
Cl
CH2CH3
YSU
4.5 Bonding in Alcohols and Alkyl Halides
Figure 4.1
YSU
5
4.5 Bonding in Alcohols and Alkyl Halides
Figure 4.2 – Electron density maps of CH3OH and CH3Cl
YSU
4.6 Physical Properties – Intermolecular Forces
CH3CH2CH3
CH3CH2F
propane fluoroethane
b.p. ‐42 oC
‐32 oC
CH3CH2OH
ethanol
78 oC
YSU
6
4.6 Physical Properties – Intermolecular Forces
Figure 4.4
YSU
4.6 Physical Properties – Intermolecular Forces
Figure 4.4
YSU
7
4.6 Physical Properties – Water Solubility of Alcohols
Alkyl halides are generally insoluble in water (useful in lab)
YSU
4.6 Physical Properties – Water Solubility of Alcohols
Solubility is a balance between polar and non‐polar characteristics
YSU
8
4.6 Physical Properties – Water Insolubility




Cholesterol – non‐polar alcohol
Limited solubility in water
Precipitates when to concentrated
Results in gallstones
Biochemistry involves a delicate balance of “like dissolves like”
YSU
4.7 Preparation of Alkyl Halides from Alcohols and H-X
R OH
alcohol
+
H X
hydrogen halide
R X
alkyl halide
+
H O H
water
Lab Conditions
YSU
9
4.8 Mechanism of Alkyl Halide Formation
Mechanism – a description of how bonds are formed and/or broken when converting starting materials (left hand side) to products (right hand side)


Usually involves solvents and reagents, sometimes catalysts
Curved arrows are used to describe the chemical changes YSU
4.8 Reaction of a Tertiary Alcohol with H-Cl
Look for chemical changes – which bonds are formed or broken?



learn the outcome of reaction in order to get going quickly
recognize the nature of the organic substrate (1o, 2o, 3o?)
be aware of the reaction conditions (acidic, basic, neutral?)
YSU
10
4.8 Reaction of a Tertiary Alcohol with H-Cl
YSU
4.8 Energetic description of mechanism - Step 1 : protonation
Figure 4.6
YSU
11
4.8 Energetic description of mechanism - Step 2 : carbocation
Figure 4.7
YSU
4.8 Energetic description of mechanism - Step 3 : trap cation
Figure 4.9
YSU
12
4.9 Full mechanism “pushing” curved arrows
H Cl
H3C
H3C C O H
H3C
H3C C Cl
H3C
H Cl
H3C H
Cl
CH3
(- H2O)
H3C C O H
H3C
(+ H2O)
H3C
H3C
C
CH3
Cl
YSU
4.9 Full SN1 mechanism showing energy changes
Figure 4.11
YSU
13
4.10 Carbocation structure and stability
Figure 4.8
YSU
4.10 Carbocation structure and stability
Figure 4.15
Hyperconjugation – the donation of electron density
from adjacent single bonds
YSU
14
4.10 Relative carbocation stability
Figure 4.12
YSU
4.11 Relative rates of reaction of R3COH with HX
Related to the stability of the intermediate carbocation:
YSU
15
4.11 Relative rates of reaction of R3COH with HX
Figure 4.16
Rate‐determining step involves formation of carbocation
YSU
4.12 Reaction of methyl- and 1o alcohols with HX – SN2
Same bonds are formed and broken as in 3o case, however;



CH3 and 1o carbon cannot generate a stabilized carbocation
kinetic studies show the rate‐determining step is bimolecular
sequence of bond‐forming/breaking events must be different
YSU
16
4.12 Reaction of methyl- and 1o alcohols with HX – SN2
Alternative pathway for alcohols that cannot form a good carbocation
YSU
4.12 Geometry changes during SN2
http://www.bluffton.edu/~bergerd/classes/cem221/sn‐e/SN2.gif
YSU
17
4.12 Energy profile for SN2 reaction
YSU
4.13 Other methods for converting ROH to RX
Cl
SOCl2
OH
PBr3

Convenient way to halogenate a 1o or 2o alcohol

Avoids use of strong acids such as HCl or HBr

Via SN2 mechanism at 1o and CH3 groups
Br
YSU
18
4.14 Free Radical Halogenation of Alkanes
heterolytic
Possible modes of bond cleavage
homolytic
YSU
4.15 Free Radical Chlorination of Methane
CH4
+
Cl2
CH3Cl
+
HCl
(~400oC)
CH3Cl
+
CH2Cl2
Cl2
+
HCl
(~400oC)
CH2Cl2
+
CHCl3
Cl2
+
HCl
(~400oC)
CHCl3
+
Cl2
CCl4
(~400oC)
+
HCl
YSU
19
4.16 Structure and stability of Free Radicals
Figure 4.17 – Bonding models for methyl radical
YSU
4.16 Structure and stability of Free Radicals

Free radical stability mirrors that of carbocations

Hyperconjugation is the main factor in stability

Experimental evidence that radicals are flat (sp2)
YSU
20
4.16 Bond Dissociation Energies (BDE)
YSU
4.16 Bond Dissociation Energies (BDE)
104 58 83.5 103
YSU
21
4.17 Mechanism for Free Radical Chlorination of Methane
YSU
4.17 Mechanism for Free Radical Chlorination of Methane
YSU
22
4.17 Mechanism for Free Radical Chlorination of Methane
YSU
4.17 Mechanism for Free Radical Chlorination of Methane
YSU
23
4.18 Free Radical Halogenation of Higher Alkanes
YSU
4.18 Free Radical Halogenation of Higher Alkanes
Radical abstraction of H is selective since the stability of the ensuing radical is reflected in the transition state achieved during abstraction.

Cl
H

CH 2CH 2CH2CH3

Cl
H

CHCH2CH3
CH3
Lower energy radical, formed faster
YSU
24
4.18 Free Radical Halogenation of Higher Alkanes
Figure 4.16
YSU
4.18 Bromine radical is more selective than chlorine radical
Consider propagation steps – endothermic with Br∙, exothermic with Cl∙
YSU
25
4.18 Bromine radical is more selective than chlorine radical
Bromination – late TS looks a lot like radical
Chlorination – early TS looks less like radical
YSU
26