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Home , Acyl halide

Organic Chemistry – The Approach

OH Br

alkane halide alkene (no F.G.)

non-polar (grease, fats) polar (water soluble) non-polar (water insoluble) non-polar (water insoluble)

tetrahedral tetrahedral tetrahedral trigonal

O NH

alkyne aromatic aldehyde/ 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

NH O HO OH H3CO OCH3 2 OH

hydrate acetal

polar (water soluble) non-polar (water insoluble) polar (water soluble) polar(watersoluble)

tetrahedral tetrahedral tetrahedral trigonal

O O O O O

OCH3 NH2 Cl O

carboxylic carboxylic 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

OH Br

alkane alcohol halide alkene (no F.G.)

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

OH Br

alkane alcohol halide alkene (no F.G.)

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 – and Halides

Figure 4.2 – Electron density maps of CH3OH and CH3Cl YSU

Alcohols and in Medicine and Nature

OH OH

Cl HN O2N Cl O Acetaminophen Valium Chloramphenicol YSU

3 4.2 IUPAC Nomenclature of Alkyl Halides • Functional class nomenclature

pentyl 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‐propanol cyclohexanol

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

4 4.4 Classes of Alcohols and Alkyl Halides

Br Primary (1o) Cl OH

OH I Secondary (2o) Cl

CH3 Br Cl Tertiary (3o) (CH3)3COH 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 CH3CH2FCH3CH2OH propane fluoroethane ethanol b.p. ‐42 oC ‐32 oC78 oC

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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 + H X R X + H O H

alcohol hydrogen halide alkyl halide water

Lab Conditions

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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

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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

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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

H3C C O H H3C C Cl (+ H2O)

H3C H3C

H Cl Cl

H3C H (- H2O) CH3 H3C C O H C H C CH H3C 3 3 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

Hyperconjugation –the donation of electron density Figure 4.15 from adjacent single bonds YSU

14 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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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;

o  CH3 and 1 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

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4.13 Other methods for converting ROH to RX

Cl SOCl2 OH PBr3 Br

 Convenient way to halogenate a 1o or 2o alcohol

 Avoids use of strong acids such as HCl or HBr

o  Via SN2 mechanism at 1 and CH3 groups YSU

18 4.14 Free Radical of Alkanes

heterolytic Possible modes of bond cleavage homolytic

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4.15 Free Radical Chlorination of Methane

CH4 + Cl2 CH3Cl +HCl (~400oC)

CH3Cl + Cl2 CH2Cl2 +HCl (~400oC)

CH2Cl2 + Cl2 CHCl3 +HCl (~400oC)

CHCl3 + Cl2 CCl4 +HCl (~400oC) 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)

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4.16 Bond Dissociation Energies (BDE)

104 58 83.5 103 YSU

21 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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22 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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23 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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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∙

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25 4.18 Bromine radical is more selective than chlorine radical

Bromination – late TS looks a Chlorination – early TS looks lot like radical less like radical YSU

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