CM1000 – Organic Chemistry

An Introduction to Functional Group Chemistry

Dr. Stuart Collins Recommended text: Hart, Craine, Hart, Organic Chemistry 11 th Edition

Course Content

• Chapter 6- Organic Halogen Compounds • Chapter 7- Alcohols, Phenols and Thiols • Chapter 9- Aldehydes and Ketones • Chapter 10- Carboxylic Acids and Their Derivatives • Chapter 11- Amines and Related Nitrogen Compounds

Organic Chemistry

Structure Reactivity Carbon Framework Functional Groups Significance?

Characteristic Behaviour - Can be rationalised and predicted Design of structure Synthesis Function

Organic Halogen Compounds

• Why important?

– CFC’s • Chlorofluorocarbons (p.196) • Environmental Impact – Insecticides (p.198) – Key Synthetic Intermediates Provide Access To A Wide Range Of Organic Compounds General Structure C X R X X = Cl, Br, I, F

Classification- Depends on Degree of Substitution

R H C X H Primary Alkyl Halide 1 o R R C X H Secondary Alkyl Halide 2 o e.g.

CH 3 -CH 2 -Br Bromoethane e.g.

CH 3 -CH-CH 3 Cl 2-chloropropane R R C X R Tertiary Alkyl Halide 3 o e.g.

H 3 C CH 3 C Cl CH 3 2-methyl-2-chloro-propane

Reactivity Strongly Influenced by Degree of Substitution

Nucleophilic Substitution R-CH 2 -X + Nu R-CH 2 -Nu + X Halide displaced by an incoming nucleophile- a species with an electron pair. Nucleophile can be neutral or anionic e.g.

OH OCH 3 CN NH 3 H O H R S R

Recall X more electronegative than C – Bond is polarised Alcohol   R-CH 2 -X R-CH 2 -Br + OH R-CH 2 -OH + Br Leaving Group One covalent bond broken (C-X) One new covalent bond (C-Nu) CH 3 -CH 2 -Cl + OCH 3 Nucleophile CH 3 CH 2 CH 2 -I + CN CH 3 -CH 2 -OCH 3 + Cl Ether CH 3 CH 2 CH 2 -CN + I Nitrile

CH 3 -CH 2 -Br + C CH Neutral Nucleophiles CH 3 -CH 2 -Br + NH 3 CH 3 CH 2 CH 2 -I + 2 CH 3 NH 2 CH 3 -CH 2 -C + Br CH 3 -CH 2 -NH 3 + Br NH 3 CH 3 -CH 2 -NH 2 + NH 4 Br CH 3 CH 2 CH 2 -NH 2 CH 3 + I CH 3 CH 2 CH 2 -NHCH 3 + CH 3 NH 3 I

CH H 3 C CH 3 C Br + H 2 O CH 3 3 -CH 2 -Cl + Na SCH 3 H 3 C CH 3 C OH 2 Br CH 3 -HBr H 3 C CH 3 C OH CH 3

t

-Butanol CH 3 -CH 2 -SCH 3 + Na Cl Sulfide or thioether

Williamson Ether Synthesis

CH CH 3 3 -CH -CH 2 2 -OH + Na -O Na + CH 3 CH 2 CH 2 Br Sodium Alkoxide + Alkyl Halide Note CH 3 CH 2 O often written as EtO CH 3 -CH 2 -O Na + 1/2 H 2 Sodium Ethoxide CH 3 CH 2 OCH 2 CH 2 CH 3 + Na Br Ethylpropyl Ether Ether + Sodium Halide

H C C

Elimination Reactions Dehydrohalogenation (6.7)

X C C + HX Loss of halide (X ) from one carbon and loss of a proton (H + ) from adjacent carbon- new alkene Usually occurs on treatment with a base e.g. Na + OEt

Bases Commonly used to Promote Elimination Reactions

1. CH 3 ONa (Sodium Methoxide) in CH 3 OH (solvent) CH 3 OH + Na CH 3 O Na + 1/2 H 2(g) 2. CH 3 CH 2 ONa (Sodium Ethoxide) in CH 3 CH 2 OH (solvent) CH 3 CH 2 OH + Na CH 3 CH 2 O Na + 1/2 H 2(g) 3. (CH 3 ) 3 COK (Potassium

t

-butoxide) in (CH 3 ) 3 COH (

t

-butanol) (CH 3 ) 3 COH + K (CH 3 ) 3 CO Na + 1/2 H 2(g) 4. NaNH 2 /NH 3(l) 5. Na OH

Mechanism

OEt H C C X Examples Tertiary Halide H CH 3 H C C H Br

t

-butyl bromide CH 3 C C + HOEt + X NaOH H CH 3 C C H CH 3 methylpropene + H 2 O + NaBr

Primary Halide KO t Bu CH 3 CH 2 CH 2 CH 2 Br CH 3 CH 2 CH H 2 C Br CH 3 CH 2 CH=CH 2 + K + Br + t BuOH CH 3 CH 2 CH=CH 2 + K + Br + (CH 3 ) 3 COH H (CH 3 ) 3 C O Secondary Halide Na OCH 2 CH 3 CH 3 CHCH 3 CH 3 CH=CH 2 + Na + Br + EtOH (CH 3 CH 2 OH) Br

Example CH 3 NaOEt EtOH Br CH 2 + + NaBr + EtOH Elimination can occur from either side of the alkyl bromide - 2 alkenes (Regioisomers) H 2 C H Br H CH 3

Cis and trans isomers can be formed in some cases Cl H CH 3 CH 3 H 3 C H 3 C H + H H 3 C CH 3 Both cis and trans isomers can be formed in the internal elimination + CH 3

Br Internal Elimination Br H Terminal Elimination Br H NaOEt EtOH +

Elimination/Substitution- May be competing reactions e.g.

CH 3 CH 2 CH 2 CH 2 Br Na OCH 2 CH 3 CH 3 CH 2 OH CH 3 CH 2 CH 2 CH 2 OCH 2 CH 3 90% + CH 3 CH 2 CH=CH 2 10% CH 3 CHCH 3 Br CH 3 O Na + CH 3 CHCH 3 OCH 3 minor + CH 3 CH=CH 2 major

By altering the reaction conditions can favour either elimination or substitution -Vary solvent (Polar/Non-Polar) -Vary base or nucleophile In general strong bases favour elimination Nucleophiles which are weak bases favour substitution