unit 4 nomenclature and properties of alkyl halides synthesis of alkyl halides reactions of alkyl...
TRANSCRIPT
Unit 4
Nomenclature and Properties of Alkyl Halides
Synthesis of Alkyl Halides
Reactions of Alkyl Halides
Mechanisms of SN1, SN2, E1, and E2 Reactions
Substrate, Nucleophilicity, and Leaving Group Effects
Alkyl Halides
Alkyl halide: a compound with a halogen atom bonded to
one of the sp3 hybrid carbon atoms of an alkyl group
Two types of names: IUPAC system Common names
Nomenclature
IUPAC System: Alkyl halides are named as an alkane with a
halo-substituent: Review the rules for naming alkanes
covered in Unit 2
CH3CH2CH2Cl
BrCH3CH2CH2Cl
Br
1-chloropropane bromocyclohexane
Nomenclature
Common Names: alkyl group name + halide
CH3CH2CH2Cl
Br
CH3CH2CH2Cl
Br
n-propyl chloride Cyclohexyl bromide
Nomenclature
Special common names: CH2X2 = methylene halide CHX3 = haloform CX4 = carbon tetrahalide
CH2Cl2 CHCl3
CCl4
chloroformtrichloromethane
Methylene chloridedichloromethane
Carbon tetrachloridetetrachloromethane
Types of Alkyl Halides
Alkyl halides can be classified by the type of carbon atom the halogen is bonded to: primary halide (1o):
halogen attached to a 1o carbon
secondary halide (2o): halogen attached to a 2o carbon
tertiary halide (3o): halogen attached to a 3o carbon
CH3CH2CH2Cl
Br
CH3CH2CH2Cl
CH3CHBr
Br
CH3
CH3CH2CH2Cl
(CH3)3CBr
Br
Types of Alkyl Halides
Geminal dihalide: 2 halogens bonded to the same carbon
atom
Vicinal dihalide: 2 halogens bonded to adjacent carbon
atoms
CH3CH2CH2Cl
(CH3)3CBr
H
Br
C
Cl
Cl
H
CH3CH2CH2Cl
(CH3)3CBr
HCH3CHCH2
Cl
Br
C
Cl
Cl
H
ClCl
Cl
Other Organic Halides Aryl halide:
halogen is attached directly to an aromatic ring
Benzylic halide halogen is attached to a carbon that is
attached to a benzene ring
C
C
CF
F
F
F
CCl
H
H
H
HO
I
I
I
I
CH2
CH
NH2
CO2H
thyroxine
CH2Cl
benzylic carbon
benzylic chloride
C
C
CF
F
F
F
CH
H
H
HO
I
I
I
I
CH2
CH
NH2
CO2H
CH2Cl
Other Organic Halides
Allylic halide: halogen is attached to a carbon that is
attached to a C=C
Allylic carbon
Allylic chloride
Other Organic Halides
Vinyl Halide: halogen attached to a carbon that is part of
a C=C
C
C
CF
F
F
F
CCl
H
H
H
HO
I
I
I
I
CH2
CH
NH2
CO2H
C
C
CF
F
F
F
CCl
H
H
H
HO
I
I
I
I
CH2
CH
NH2
CO2H
Monomer for PVC Monomer for teflon
Uses of Alkyl Halides
Anesthetics: Chloroform (CHCl3)
toxic carcinogenic (causes cancer)
Solvents: CCl4
formerly used in dry cleaning CH2Cl2
formerly used to decaffeinate coffee liquid CO2 used now
Uses of Alkyl Halides
Freons: Freon-12: CF2Cl2
Freon-22: CHClF2
Freon-134a:
Pesticides:
Cl C
Cl
Cl
C
H
Cl
Cl
DDT
Cl C
Cl
Cl
C
H
Cl
Cl
Cl Cl
Cl
ClCl
Cl
Cl ClChlordane (termites)
C CF
F
F
F
H
H
Physical Properties
Boiling Point: Compounds with higher MW’s and greater
surface area (more linear) tend to have higher BP.
BP increases as size of halogen increases F < Cl < Br < I
BP decreases as branching increases
Physical Properties
Density: Alkyl chlorides are common solvents for
organic reactions.
CH2Cl2
CHCl3
CCl4
More dense than water
Preparation of Alkyl Halides
Alkyl halides can be prepared from a variety of starting materials including alkanes, alkenes, alkynes, alcohols, and other alkyl halides.
You are responsible for knowing and applying the synthesis of R-X by: free radical halogenation reactions free radical allylic bromination reactions
Preparation of Alkyl Halides
Free Radical Halogenation of Alkanes
alkane + X2 alkyl halide(s) + HX
Limited utility due to generally poor selectivity and yield. Useful when only one type of reactive hydrogen
is present
Bromination is more selective and gives the product formed from the most stable free radical.
hor
Preparation of Alkyl Halides
Useful Examples:
+ Cl2 + HCl
CH3 CH3+ Br2
Cl
C
CH3
CH3
H C
CH3
CH3
Br
h
h
50 %
90 %
+ Cl2 + HCl
CH3 CH3+ Br2+ HBr
Cl
C
CH3
CH3
H C
CH3
CH3
Br
Preparation of Alkyl Halides
Free Radical Allylic Bromination:
where NBS = N-bromosuccinimide
C + NBS CCC
H
CC
Br
h
+ HBr N
O
O
Br N
O
O
H + Br2
NBS
Preparation of Alkyl Halides
Allylic bromination more selective
allylic free radical is resonance stabilized
Addition of Br2 to the double bond is a competing reaction
use low levels of Br2 by generating it “in situ” using NBS
HH
H
HH
H
HH
H
HH
H
Preparation of Alkyl Halides
Examples:
+ NBS
Br
h
+ NBS
+ NBS
+ NBS
Br
Br
Br
h
Reactions of RX
Most reactions of alkyl halides involve breaking the C-X bond. Nucleophilic substitution Elimination
The halogen serves as a leaving group in these reactions: nucleophile can attack the carbon bearing
the +
the halogen can leave as X-, taking the bonding electrons with it
C X+ -
Reactions of RX
Nucleophilic substitution: reaction in which a nucleophile replaces a
leaving group
Nucleophile: electron pair donor
Leaving group: an atom or group of atoms that are lost during
a substitution or elimination reaction retains both electrons from the original bond
Reactions of RX
General Equation for Nucleophilic Substitution
Example:
C
C + X
+ CH3O
C
H
X + Nuc C Nuc
Br OCH3-+ Br-
-C C + X
CH2Cl
C X + Nuc C Nuc-
Reactions of RX
Elimination Reaction: two substituents are lost from adjacent
(usually) carbons, forming a new bond
Dehydrohalogenation: an elimination reaction in which H+ and X-
are lost, forming an alkene
C CC CH3
H
H
H CH3
Br
CH
H
CH3
CH3
C CC CH3
H
H
H CH3
Br
CH
H
CH3
CH3
CH3O-
Reactions of RX There are two common types of nucleophilic
substitution reactions: SN1 reactions
substitution, nucleophilic, unimolecular 3o, allylic, benzylic halides weak nucleophiles
SN2 reactions substitution, nucleophilic, bimolecular
methyl and 1o halides strong nucleophiles
Reactions of RX
Reactions of RX
Common strong nucleophiles: hydroxide ion alkoxide ions many amines iodide and bromide ions cyanide ion
Common weak nucleophiles: water alcohols fluoride ion
SN2 Reactions
The reaction between methyl iodide and hydroxide ion is a concerted reaction that takes places via an SN2 mechanism
HO + H HOC
H
H
I C
H
H
H + I- -
nucleophile
substrate product Leaving group
Substrate: the compound attacked by a reagent
(nucleophile)
SN2 Reactions
Concerted reaction: a reaction that takes place in a single step
with bonds breaking and forming simultaneously
SN2: substitution, nucleophilic, bimolecular transition state of rate-determining step
involves collision of 2 molecules 2nd order overall rate law
Rate = k[RX][Nuc]
SN2 Reactions
SN2 Mechanism: Nucleophile attacks the back side of the
electrophilic carbon, donating an e- pair to form a new bond
Since carbon can only have 8 valence electrons, the C-X bond begins to break as the C-Nuc bond begins to form
Nuc C Nuc C X
Nuc + X
H
HH X
H
HH
CH
HH
Nuc C Nuc C X
Nuc + X
H
HH X
H
HH
CH
HH
---
SN2 Reactions SN2 Mechanism for the reaction of methyl iodide and
hydroxide ion:
HO C
HO
HOI
H
HH
C I
HH
H
CH
HH
HO C
HO
HOI
H
HH
C I
HH
H
CH
HH
-
HO C HO
C HO C I
I
H
HH
H
CH
HH
HH
-
HO C
HO
HOI
H
HH
C I
HH
H
CH
HH
+ I -
SN2 Reactions
Reaction Energy Diagram: large Ea due to 5-coordinate carbon atom in
transition state no intermediates
exothermic
SN2 Reactions
SN2 reactions occur with inversion of configuration at the electrophilic carbon. The nucleophile attacks from the back side
(the side opposite the leaving group). Back-side attack turns the tetrahedron of
the carbon atom inside out.
SN2 Reactions
Inversion of configuration: a process in which the groups bonded to a
chiral carbon are changed to the opposite spatial configuration:
R S or S R
SN2 Reactions
Example: Predict the product formed by the SN2 reaction between (S)-2-bromobutane and hydroxide ion. Draw the mechanism for the reaction.
SN2 Reactions
The SN2 displacement reaction is a stereospecific reaction a reaction in which a specific stereoisomer
reacts to give a specific diastereomer of the product
H
CH3
Br
H
H
CH3
H
Br
H H
BrCH3
H
CH3
Br
H
H
CH3
H
Br
H
HCH3
OH+ OH-
Br
OH
H
CH3
Br
H
H
CH3
H
Br
HH
CH3
+ Br -
SN2 Reactions
SN2 reactions occur under the following conditions Nucleophile:
strong, unhindered nucleophile OH- not H2O CH3O- not CH3OH CH3CH2O- not (CH3)3CO-
Substrate: 1o or methyl alkyl halide (most favored) 2o alkyl halide (sometimes) 3o alkyl halides NEVER react via SN2
SN2 Reactions
The relative rate of reactivity of simple alkyl halides in SN2 reactions is:
methyl > 1o > 2o >>>3o
3o alkyl halides do not react at all via an SN2 mechanism due to steric hinderance. The back side of the electrophilic carbon
becomes increasingly hindered as the number or size of its substituents increases
SN2 Reactions
Steric hinderance at the electrophilic carbon:
SN2 Reactions
SN2 reactions can be used to convert alkyl halides to other functional groups: RX + I - R-I RX + OH- R-OH RX + R’O- R-OR’ RX + NH3 R-NH3
+ X-
RX + xs NH3 R-NH2
RX + CN- R-CN RX + HS- R-SH RX + R’S- R-SR’ RX + R’COO- R’CO2R
KNOW THESE!
Be able to apply these!
SN2 Reactions
Example: Predict the product of the following reactions:
(CH3)
2CHCH
2CH
2Cl + NH
3 (xs)
CH3CH
2CH
2CH
2Cl + NaCN
(CH3)
2CHCH
2CH
2Cl + NH
3 (xs)
CH3CH
2CH
2CH
2Cl + NaCN
SN2 Reactions
Example: What reagent would you use to do the following reactions:
(CH3)
2CHCH
2CH
2Cl + NH
3 (xs)
CH3CH
2CH
2CH
2Cl + NaCN
CH3CH2CH2Br + CH3CH2CH2OCH2CH3?
(CH3)
2CHCH
2CH
2Cl + NH
3 (xs)
CH3CH
2CH
2CH
2Cl + NaCN
CH3CH2CH2Br + CH3CH2CH2OCH2CH3
CH3CH2I + CH3CH2C CH?