1 Organic Chemistry The Functional Group Approach Br OH alkane - - PDF document

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Organic Chemistry – The Functional Group Approach

alkane (no F.G.) non-polar (grease, fats) tetrahedral

OH

alcohol polar (water soluble) tetrahedral

Br

halide non-polar (water insoluble) tetrahedral alkene non-polar (water insoluble) trigonal alkyne non-polar (water insoluble) linear aromatic non-polar (water insoluble) flat aldehyde/ketone polar (water soluble) trigonal imine polar (water soluble) trigonal

O NH

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Organic Chemistry – The Functional Group Approach

OCH3

carboxylic ester polar (water-solube) trigonal

NH2

carboxylic amide polar (water soluble) trigonal

Cl

acyl halide non-polar (reacts w/water) trigonal

O

acid anhydride non-polar (reacts w/water) trigonal

O O O O O

hydrate polar (water soluble) tetrahedral acetal non-polar (water insoluble) tetrahedral amine polar (water soluble) tetrahedral

OH

carboxylic acid polar (water soluble) trigonal

NH2 O HO OH H3CO OCH3

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Organic Chemistry – The Functional Group Approach

alkane (no F.G.) non-polar (grease, fats) tetrahedral

OH

alcohol polar (water soluble) tetrahedral

Br

halide non-polar (water insoluble) tetrahedral alkene non-polar (water insoluble) trigonal alkyne non-polar (water insoluble) linear aromatic non-polar (water insoluble) flat aldehyde/ketone polar (water soluble) trigonal imine polar (water soluble) trigonal

O NH

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Organic Chemistry – The Functional Group Approach

alkane (no F.G.) non-polar (grease, fats) tetrahedral

OH

alcohol polar (water soluble) tetrahedral

Br

halide non-polar (water insoluble) tetrahedral alkene non-polar (water insoluble) trigonal alkyne non-polar (water insoluble) linear aromatic non-polar (water insoluble) flat aldehyde/ketone polar (water soluble) trigonal imine polar (water soluble) trigonal

O NH

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Carey Chapter 4 – Alcohols and Alkyl Halides

Figure 4.2 – Electron density maps of CH3OH and CH3Cl

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Alcohols and Halogens in Medicine and Nature

Chloramphenicol Acetaminophen

O2N HN O OH OH Cl Cl

Valium

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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 YSU

4.3 IUPAC Nomenclature for Alcohols

1‐pentanol cyclohexanol 2‐propanol 2‐pentanol 1‐methyl cyclohexanol 5‐methyl‐2‐heptanol

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4.4 Classes of Alcohols and Alkyl Halides

Cl OH Br OH I Cl Br CH3 (CH3)3COH CH2CH3 Cl Primary (1o) Secondary (2o) Tertiary (3o) YSU YSU

4.5 Bonding in Alcohols and Alkyl Halides

Figure 4.1

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4.5 Bonding in Alcohols and Alkyl Halides

Figure 4.2 – Electron density maps of CH3OH and CH3Cl

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4.6 Physical Properties – Intermolecular Forces

CH3CH2CH3 CH3CH2F CH3CH2OH

propane fluoroethane ethanol

b.p. ‐42 oC ‐32 oC 78 oC

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4.6 Physical Properties – Intermolecular Forces

Figure 4.4

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4.6 Physical Properties – Intermolecular Forces

Figure 4.4

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4.6 Physical Properties – Water Solubility of Alcohols

Alkyl halides are generally insoluble in water (useful in lab)

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4.6 Physical Properties – Water Solubility of Alcohols

Solubility is a balance between polar and non‐polar characteristics

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4.6 Physical Properties – Water Insolubility

Biochemistry involves a delicate balance of “like dissolves like”

 Cholesterol – non‐polar alcohol  Limited solubility in water  Precipitates when to concentrated  Results in gallstones

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4.7 Preparation of Alkyl Halides from Alcohols and H-X

R OH + H X R X + H O H alcohol hydrogen halide alkyl halide water

Lab Conditions

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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 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?)

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4.8 Reaction of a Tertiary Alcohol with H-Cl

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4.8 Energetic description of mechanism - Step 1 : protonation

Figure 4.6

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4.8 Energetic description of mechanism - Step 2 : carbocation

Figure 4.7

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4.8 Energetic description of mechanism - Step 3 : trap cation

Figure 4.9

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4.9 Full mechanism “pushing” curved arrows

H3C C H3C H3C O H H Cl H3C C H3C H3C Cl H3C C H3C H3C O H H C CH3 H3C CH3 Cl Cl (+ H2O) H Cl (- H2O)

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4.9 Full SN1 mechanism showing energy changes

Figure 4.11

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4.10 Carbocation structure and stability

Figure 4.8

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Hyperconjugation – the donation of electron density from adjacent single bonds

4.10 Carbocation structure and stability

Figure 4.15

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4.10 Relative carbocation stability

Figure 4.12

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4.11 Relative rates of reaction of R3COH with HX

Related to the stability of the intermediate carbocation:

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4.11 Relative rates of reaction of R3COH with HX

Rate‐determining step involves formation of carbocation

Figure 4.16

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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

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4.12 Reaction of methyl- and 1o alcohols with HX – SN2

Alternative pathway for alcohols that cannot form a good carbocation

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4.12 Geometry changes during SN2

http://www.bluffton.edu/~bergerd/classes/cem221/sn‐e/SN2.gif

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4.12 Energy profile for SN2 reaction

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4.13 Other methods for converting ROH to RX

OH PBr3 Br SOCl2 Cl

 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

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4.14 Free Radical Halogenation of Alkanes

heterolytic homolytic Possible modes of bond cleavage

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4.15 Free Radical Chlorination of Methane

CH4 + Cl2 CH3Cl + Cl2 (~400oC) CH2Cl2 + Cl2 CHCl3 + Cl2 (~400oC) (~400oC) (~400oC) CH3Cl + HCl CH2Cl2 + HCl CHCl3 + HCl CCl4 + HCl

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4.16 Structure and stability of Free Radicals

Figure 4.17 – Bonding models for methyl radical YSU 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)

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4.16 Bond Dissociation Energies (BDE)

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4.16 Bond Dissociation Energies (BDE)

104 58 83.5 103

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4.17 Mechanism for Free Radical Chlorination of Methane

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4.17 Mechanism for Free Radical Chlorination of Methane

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4.17 Mechanism for Free Radical Chlorination of Methane

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4.17 Mechanism for Free Radical Chlorination of Methane

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4.18 Free Radical Halogenation of Higher Alkanes

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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 CH2CH2CH2CH3   Cl H CHCH2CH3   CH3 Lower energy radical, formed faster

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4.18 Free Radical Halogenation of Higher Alkanes

Figure 4.16

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4.18 Bromine radical is more selective than chlorine radical

Consider propagation steps – endothermic with Br∙, exothermic with Cl∙

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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