1. Unit 4 – Alkyl Halides, Nucleophilic Substitution, and Elimination Reactions
Nomenclature and Properties of Alkyl Halides
Synthesis of Alkyl Halides
Reactions of Alkyl Halides
Mechanisms of SN1, SN2, E1, and E2 Reactions
Nucleophilicity, Substrate, and Leaving Group Effects

2. Alkyl Halides Alkyl halide:
a compound with a halogen atom bonded to one of the sp3 hybridized carbon atoms of an alkyl group
Two types of names:
IUPAC system
Common names

3. Nomenclature 1-chloropropane bromocyclohexane IUPAC System:
Alkyl halides are named as an alkane with a halo-substituent:
Review the rules for naming alkanes covered in Unit 2
1-chloropropane
bromocyclohexane

4. Nomenclature n-propyl chloride Cyclohexyl bromide Common Names:
alkyl group name + halide
n-propyl chloride
Cyclohexyl bromide

5. Nomenclature CH2Cl2 CHCl3 Methylene chloride dichloromethane
Special common names:
CH2X2 = methylene halide
CHX3 = haloform
CX4 = carbon tetrahalide
CH2Cl2
CHCl3
Methylene chloride
dichloromethane
chloroform
trichloromethane
CCl4
Carbon tetrachloride
tetrachloromethane

6. 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

7. Types of Alkyl Halides Geminal dihalide:
2 halogens bonded to the same carbon atom
Vicinal dihalide:
2 halogens bonded to
adjacent carbon atoms

8. Other Organic Halides thyroxine benzylic carbon benzylic chloride
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
thyroxine
benzylic carbon
benzylic chloride

9. Other Organic Halides Allylic carbon Allylic chloride Allylic halide:
halogen is attached to a carbon that is attached to a C=C
Allylic carbon
Allylic
chloride

10. Other Organic Halides Vinyl Halide:
halogen attached to a carbon that is part of a C=C
Monomer for PVC
Monomer for teflon

11. 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

12. Uses of Alkyl Halides DDT Chlordane (termites) Freons:
Freon-12: CF2Cl2
Freon-22: CHClF2
Freon-134a:
Pesticides:
DDT
Chlordane (termites)

13. 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

14. Physical Properties More dense than water Density:
Alkyl chlorides are common solvents for organic reactions.
CH2Cl2
CHCl3
CCl4
More dense than water

15. 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

16. Preparation of Alkyl Halides
Free Radical Halogenation of Alkanes
alkane + X alkyl halide(s) + HX
Poor selectivity and moderate yields often limit usefulness.
Bromination is more selective and gives the product formed from the most stable free radical.
Chlorination is useful when only one type of reactive hydrogen is present
hu or D

17. Preparation of Alkyl Halides
Useful Examples: hu
50 %

18. Preparation of Alkyl Halides
The following free radical halogenation is doomed to failure!
The following addition reaction occurs instead:

19. Preparation of Alkyl Halides
Free Radical Allylic Bromination:
where NBS = N-bromosuccinimide hn
NBS

20. Preparation of Alkyl Halides
NBS is used to generate low levels of Br2 in situ.
Minimizes addition of bromine across the C=C
Allylic bromination is highly selective and occurs in the allylic position due to resonance stabilization of the resulting free radical.

21. Preparation of Alkyl Halides
Examples: hu hu

22. 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.
the halogen leaves as X-, taking the bonding electrons with it d+ d-

23. 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

24. Reactions of RX General Equation for Nucleophilic Substitution
The nucleophile can be neutral or negatively charged, but it must have at least one lone pair of electrons.
Example:

25. Reactions of RX Elimination Reaction:
two substituents are lost from adjacent (usually) carbons, forming a new p bond
Dehydrohalogenation:
an elimination reaction in which H+ and X- are lost, forming an alkene
CH3O-

26. 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

27. Reactions of RX

28. 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

29. SN2 Reactions
The reaction between methyl iodide and hydroxide ion is a concerted reaction that takes places via an SN2 mechanism
nucleophile
Leaving group
substrate
product
Substrate:
the compound attacked by a reagent (nucleophile)

30. 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]

31. 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

32. SN2 Reactions
SN2 Mechanism for the reaction of methyl iodide and hydroxide ion:

33. SN2 Reactions Reaction Energy Diagram:
large Ea due to 5-coordinate carbon atom in transition state
no intermediates
exothermic

34. 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.

35. 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

36. SN2 Reactions
Example: Predict the product formed by the SN2 reaction between (S)-2-bromobutane and sodium cyanide. Draw the mechanism for the reaction.

37. 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

38. 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

39. methyl > 1o > 2o >>>3o
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

40. SN2 Reactions
Steric hinderance at the electrophilic carbon:

41. SN2 Reactions KNOW THESE! Be able to apply these!
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!

42. SN2 Reactions
Example: Predict the product of the following reactions:

43. SN2 Reactions
Example: What reagent would you use to do the following reactions: ? ?