Halogen Containing Organic Compounds

ALKYL HALIDES

Preparation

1. From Alcohols (Replacement of OH by X)

ROH R-X.

2. Halogenation of Hydrocarbons

R-H R-X + HX


3. Addition of Hydrogen Halides to Alkenes (Discussed under alkenes)





4. Addition of Halogens to Alkenes and Alkynes



5. Halide Exchange


R-X + I^- RI + X^-

Nucleophilic Substitution

The order of reactivity is RI>RBr>RCl>RF.

RX + ^-OH ROH + X^- Alcohol
RX + H₂O ROH Alcohol
RX + ^-OR' R OR' Ether
(Williamson synthesis)

RX + ^-C CR' R - C CR'    Alkyne
RX + I^- RI    Alkyl iodide
RX + ^-CN RCN    Nitrile

RX + R'COO^- R¢ - - OR     Ester

RX + :NH₃ RNH₂       Primary amine

RX + :NH₂R' RNHR'      Secondary amine

RX + :NH R'R" RNR'R''      Tertiary amine

RX + SH^- RSH      Thiol (mercaptan)

RX + :SR^' RSR'      Thioether (sulfide)

RX + ArH + AlCl₃ Ar R      Alkyl benzene
(Friedel Craft reaction)

Nucleophilic Displacement by S_N1 and S_N2 Mechanisms

S_n2 Reaction

1. Mechanism:



2. Kinetics:

The reaction between methyl bromide and hydroxide ion to yield methanol follows second order kinetics; that is, the rate depends upon the concentrations of both reactants :

CH₃Br +^-OH CH₃OH + Br^-

rate = K [CH₃Br] [OH^-]


3. Stereochemistry:
A reaction that yields a product whose configuration is opposite to that of the reactant is said to proceed with inversion of configuration.







4. Reactivity:

In SN₂ reactions the order of reactivity of RX is CH₃X>1^o>2^o>3^o.


S_n1 Reaction

Mechanism and Kinetics
The reaction between tert-butyl bromide and hydroxide ion to yield tert-butyl alcohol follows first order kinetics; i.e., the rate depends upon the concentration of only one reactant,
tert-butyl bromide.





S_N1 reaction follows first order kinetics.

Nucleophilic Displacement By S_N1 And S_N2 Mechanisms

	SN1	SN2
–Steps	Two : (1) R:XR+ + X- (2) R+ + Nu- RNu or R+ + :Nu RNu+	One : R:X + Nu- RNu + X- or R:X + Nu RNu+ X-
Rate	=K [RX] (1st order)	=K[RX] [:Nu‑] (2nd order)
TS of slow step	| Cd+......Xd-
Stereochemistry	Inversion and racemization	Inversion (backside attack)
Molecularity	Unimolecular	Bimolecular
Reactivity structure of R Determining factor Nature of X Solvent effect on rate	3o> 2o> 1o> CH3 Stability of R+ ; RI> RBr> RCl> RF Rate increases in polar solvent	CH3> 1o> 2o> 3o Steric hindrance in R group RI> RBr> RCl> RF with Nu- there is a large rate increase in polar aprotic solvents.
Effect of nucleophile		Rate depends on nucleophilicity I- > Br- > Cl- ; RS- > RO-
Catalysis	Lewis acid, eg. Ag+, AlCl3, ZnCl2	None
Competition reaction	Elimination, rearrangement	Elimination

Stereochemistry

When (-)-2-bromo octane is converted into the alcohol under conditions where first-order kinetics are followed, partial racemization is observed.

The optically active bromide ionizes to form bromide ion and the flat carbocation. The nucleophilic reagent then attaches itself to carbonium ion from either face of the flat ion.

If the attack were purely random, we would expect equal amounts of two isomers; i.e. we would expect only the racemic modification. But the product is not completely racemized, for the inverted product exceeds its enantiomer.


We can say in contrast to S_N2 reaction, which proceeds with complete inversion; an S_N1 reaction proceeds with racemization though may not be complete.




S_N1 reaction follows first order kinetics.

Nucleophilic Displacement By S_N1 And S_N2 Mechanisms

	SN1	SN2
Carbonium ion	Two : (1) R:XR+ + X- (2) R+ + Nu- RNu or R+ + :Nu RNu+	One : R:X + Nu- RNu + X- or R:X + Nu RNu+ X-
Rate	=K [RX] (1st order)	=K[RX] [:Nu‑] (2nd order)
TS of slow step	| Cd+......Xd-
Stereochemistry	Inversion and racemization	Inversion (backside attack)
Molecularity	Unimolecular	Bimolecular
Reactivity structure of R Determining factor Nature of X Solvent effect on rate	3o> 2o> 1o> CH3 Stability of R+ RI> RBr> RCl> RF Rate increases in polar solvent	CH3> 1o> 2o> 3o Steric hindrance in R group RI> RBr> RCl> RF with Nu- there is a large rate increase in polar aprotic solvents.
Effect of nucleophile		Rate depends on nucleophilicity I- > Br- > Cl- ; RS- > RO-
Catalysis	Lewis acid, eg. Ag+, AlCl3, ZnCl2	None
Competition reaction	Elimination, rearrangement	Elimination

Stereochemistry

When (-)-2-bromo octane is converted into the alcohol under conditions where first-order kinetics are followed, partial racemization is observed.

The optically active bromide ionizes to form bromide ion and the flat carbocation. The nucleophilic reagent then attaches itself to carbonium ion from either face of the flat ion.
If the attack were purely random, we would expect equal amounts of two isomers; i.e. we would expect only the racemic modification. But the product is not completely racemized, for the inverted product exceeds its enantiomer.

We can say in contrast to S_N2 reaction, which proceeds with complete inversion; an S_N1 reaction proceeds with racemization though may not be complete.


r.d.s formation of carbonium ion.

Reactivity of an alkyl halide depends chiefly upon how stable a carbonium ion it can form.


In S_N1 reactions the order of reactivity of alkyl halides is Allyl,benzyl>3^o>2^o>1^o>CH₃ X.