ALKYL HALIDES by Parinya Theramongkol Department of Chemistry Khon Kaen University

Structure : The Functional Group R-X Alkyl groupHalogen atom เป็นตัวกำหนดลักษณะ เชิงโครงสร้างและ ควบคุมคุณสมบัติของ สาร The Functional Group

Classification & nomenclature แบ่งตามชนิดของอะตอมคาร์บอนที่ แฮโลเจนเกาะอยู่

Common vs IUPAC names commonIUPAC n-Butyl bromide 1-Bromobutane Isopropyl chloride2-Chloropropane Isobutyl chloride 1-Chloro-2-methylpropane (1o)(1o) (1o)(1o) (2o)(2o)

3-Chloro-2-methylpentane 4-Bromo-2,4-dimethylhexane (2 o ) (3 o ) ?

PREPARATION 1. From alcohols

2. Halogenation of certain hydrocarbons

3. Addition of hydrogen halide to alkenes 4. Addition of halogens to alkenes and alkynes

5. Halide exchange Notes on preparation : •The most general and practical way to make RX is to prepare from alcohols. •RXs are almost never prepared by direct halogenation of alkanes. •RI is often prepared from the corresponding bromide or chloride by treatment with a solution of NaI in acetone.

REACTIONS 1.Nucleophilic aliphatic substitution   Nucleophilic site Electrophilic site

Nucleophilic substitution See more examples on text p.174

2. Dehydrohalogenation : elimination 3. Preparation of Grignard reagent

4. Reduction M = Li, Na, K

The S N 2 Reaction: Kinetics : the concentrations of both reactants the reaction rate  Second - order kinetics substitution nucleophilic bimolecular

Mechanism & stereochemistry of S N 2 reaction Nucleophile attacks on the back-side of the C-X bond Bond-making and bond-breaking occur simultaneously Product has a complete inversion of configuration

S N 2 Reactivity.Steric hindrance Reactivity : CH 3 W > 1 o > 2 o > 3 o

The S N 1 Reaction: substitution nucleophilic unimolecular Kinetics : the concentration of alkyl halide the reaction rate  First - order kinetics

Mechanism & stereochemistry of S N 1 reaction Step 1 : ionization = rate determining step Step 2 : combination

A reactive intermediate which is a group of atoms that contains a carbon atom bearing only 6 electrons. CARBOCATION sp 2 empty p-orbital Structure of carbocation

Mechanism & stereochemistry of S N 1 reaction Ionization of the C-X bond to generate a carbocation is the rate determining step. Reaction proceeds with racemization. Optically active Opposite configuration ; Lower optical purity S N 1 : racemization plus inversion

H2OH2O (b) retension (a) Inversion (predominates)

S N 1 Reactivity.Ease of formation of carbocation Relative Rate (S N 1) Reactivity in S N 1 : 3 o > 2 o > 1 o > CH 3 W Rate of formation of C+ : 3 o > 2 o > 1 o > CH 3 +

Stabilization of C+ : Polar effects Polar effects : ผลที่เกิดขึ้นตรงจุดเกิดปฏิกริยา อันเนื่องมาจาก การให้หรือรับอิเล็คตรอนของกลุ่มข้างเคียง stability Charge dispersion G = e - donating group G = e - withdrawing group Disperses charge Stabilizes cation intensifies charge Destabilizes cation

Rearrangement of carbocations A less stable C+ can rearrange itself in order to become a more stable C+. rearrangement No rearrangement rearrangement

1,2-shifts Two common migrations are a hydride shift and an alkyl shift Migratory mode : A hydride shift An alkyl shift

SN1SN1S N 2 vs. (a) second-order kinetics (b) complete stereochemical inversion (c) absence of rearrangement (d) the reactivity sequence CH 3 W > 1 o > 2 o > 3 o (a) first-order kinetics (b) racemization (c) rearrangement (d) the reactivity sequence 3 o > 2 o > 1 o > CH 3 W SN2SN2 SN1SN1