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Chapter 6: Alkyl Halides: Nucleophilic Substitution and Elimination
I)Basic Terminology
A)Alkyl Halide - halogens attached to a sp3 hybrid carbon atom.
B)Vinyl Halide - halogens attached to a sp2 hybrid carbon atom (i.e., an alkene).
C)Aryl Halide - halogens attached to a sp2 hybrid carbon atom of an aromatic ring.
II)Nomenclature
A)IUPAC - name them as haloalkanes (F = fluoro-, Cl = chloro-, Br = bromo-, I = iodo- ). Rest of earlier rules are the same.
B)Common or Trivial Names follow the title of the chapter, i.e., alkyl halides
Example:CH3Imethyl iodide
CH3CH2Brethyl bromide
(CH3)3CCltert-butyl chloride
C)Some names are just plain strange, i.e.,
Example:CH2Cl2methylene chloride (dichloromethane)
CHCl3chloroform (trichloromethane)
CCl4carbon tetrachloride
D)Geminal Dihalides - two halogens bonded to the same carbon atom.
E)Vicinal Dihalide - two halogen bonded to adjacent carbons.
III)Physical Properties of Alkyl Halides
A)Physical properties are determined by the following forces.
- London forces - found in all molecules.
- Dipole-dipole attraction - due to highly polar nature of the C-X bond where we have a partial positive dipole on the carbon and a partial negative dipole on the more electronegative halogen.
B)Branched versus straight chain molecules
- Just as in the alkanes, branching of alkyl halides decreases boiling and freezing points when compared to their straight chain isomers of equal molecular weight.
- Be familiar with density trends for mono- and poly- substituted alkyl halides. This is very useful to know since many of these are common organic solvents.
IV)Preparation of Alkyl Halides
A)Chapter 4.
- We have seen that X2 under conditions of light (h) or heat ( ) adds a halogen to an alkane. The problem with this method is that one ends up with a mixture of mono-, di-, tri- etc. substituted products unless great care is taken).
B)New Methods
- Allylic Halogenation (works especially well for brominations).
a) Allylic carbons and its hydrogens are those attached to the C=C group.
b) Mechanism - no real changes from chapter 4 except for resonance stabilization of the intermediate allylic free radical.
c) Want a low [Br2 ] because an excess would cause bromination at the C=C site. To minimize this, one uses N-bromosuccinimide (NBS). The advantage of using NBS is summarized by the following reaction.
Bromine is regenerated and can therefore undergo another initiation cycle.
- Benzylic Halogenation
a)Another resonance stabilized free radical (benylic free radical), named because it is derived from a benzene (aromatic) ring.
b)Examples:
c)Mechanism is the same, also have resonance stabilization just as in allylic case (Note: Resonance forms for both are shown).
d)Again, we need a low concentration of bromine (bromine readily adds across a double bond). This requirement is best accomplished using NBS.
Review Summary Table (Preparation of Alkyl Halides)
Reactions of Alkyl Halides
- Substitution - type of reaction that involves one atom replacing the halide ion.
- Elimination - type of reaction in which the halide ion leaves with another atom or ion (often H+ ).
a)In many elimination reactions, a molecule of H-X is lost from the alkyl halide to form an alkene. Such a reaction is a dehydrohalogenation.
b)Since most nucleophiles are basic, substitution and elimination reactions often occur in competition with each other (the predominant reaction will depend upon the alkyl halide present and the reaction conditions).
We have 4 important reaction mechanisms that are summarized as follows:
A)SN2 - Substitution, Nucleophilic, Bimolecular
General Reaction:Nuc-: + R-L Nu-R + :L
Kinetics:2nd Order OverallRate = k[Nuc-: ][R-L ]
Mechanism:Concerted Reaction (occurs in one step)
Stereochemistry: get inversion of configuration (Walden Inversion).
Only can be observed if using stereoisomers.
Reaction Conditions: Reaction goes best in aprotic solvents (aprotic solvents have no -OH or -NH groups). Type of substrate preferred follows the trend
methyl > 1o > 2o > 3o where 3o substrates do not go via SN2 at all.
General Shape of Energy vs. Reaction Coordinate Diagram:
If the nucleophile is neutral, then we have the following:
B)SN1 - Substitution, Nucleophilic, Unimolecular
General Reaction:Nuc : + R-L R-Nuc + :L
Kinetics:First order overallRate = k [ R-L ]
Note that reaction rate does not depend on nucleophile concentration ! This means that nucleophile must react after the rate determining step.
Mechanism:Occurs step-wise, first step is slow - goes via a carbocation intermediate.
Second step is the nucleophile attacking the carbocation (attack may occur from either front or back side).
Stereochemistry: Enantiomers Racemate (racemic mix.)
Reaction Conditions: Reaction goes best in polar protic solvents (protic solvents contain -OH and -NH groups).
Type of Substrate:3o > 2o > 1o > methyl
1o and methyl do not go via carbocation intermediate.
Reaction Coordinate Diagram:
Additional Information:
Allylic halides undergo rapid SN1 reactions due to resonance stabilization of the carbocation.
Added Problem: Get hydride and methide shifts to form more stable carbocations before the nucleophile attacks, (get skeletal rearrangements).
Comparison of SN1 & SN2 Reactions
- Nucleophile:
SN1 - nucleophile is unimportant.
SN2 - nucleophile is very important. Want strong nucleophiles since rate of reaction depends on its concentration
Strength of nucleophiles can be determined as follows:
a)Negatively charged nucleophiles are stronger than their conjugate acids ( A - > HA)
b)If the same atom is involved, then strength follows basicity ( RO - > OH - > RCO2 - > ROH > HOH)
c)Strength increases as we go down a column.
d)Strength decreases as we go across a period.
e)Halogens: I - > Br - > Cl - > F - due to the increase in size and polarizability. This series can be reversed under some conditions.
- Substrate
SN1 substrates -3o > 2o > 1o > methyl
1o and methyl do not undergo SN1
SN2 substrates -methyl > 1o > 2o > 3o
3o does not undergo SN2
- Solvent
SN1 favored by polar protic solvents since they stabilize (solvate ions) well
SN2 favored by polar aprotic solvents (no OH or NH groups)
- Leaving Groups
Weak bases are the best leaving groups. Best ones at the moment are sulfonates like TsO - or p-toluenesulfonate ion
C)E2 - Elimination, Bimolecular
General Reaction:B:- + RCH2CH2X RCH=CH2 + BH + :X -
Kinetics: 2nd order overallRate = k [B:-] [RCH2CH2X]
Mechanism: Concerted reaction, with a co-planar arrangement of orbitals. Transition state must be anti-periplanar or anti-coplanar- i.e., the two carbons, H and X must all be in the same plane with H and X on opposite sides. In a six membered ring H and X must both be axial; for any ring system they must be trans to each other. We call this requirement trans-diaxial with some textbooks call this alpha, beta, or 1,2-elimination.
E2 mechanism follows Saytzeff rule (one gets the most highly substituted double bond in greatest yield). We will also see later on that this is also the stability order for the alkenes.
For disubstituted alkenes, trans is more stable than cis.
Energy vs. Reaction Coordinate Diagram is the same as what we saw for SN2.
D) E1Elimination, Unimolecular
General Reaction: B:- + RCHXCH3 RCH=CH2 + BH + :X -
Kinetics: 1st order overallRate = k [RCHXCH3]
Mechanism: Occurs step-wise where first step is slow- goes via a carbocation intermediate. Thus we have:
Once again we usually get the more substituted double bond. However, there is no restriction on its stereochemistry (unlike the E2).
General shape of the energy vs. reaction coordinate diagram is similar to the SN1 case. Note that the rate determining step is independent of concentration of the attacking base.
Usually E1 is only a minor reaction accompanying the SN1 reaction.
Comparison of E1 and E2 reactions:
a)Base:
E2:Requires strong bases.
E1:Base strength does not matter.
b)Solvent
E2:Solvent is relatively unimportant.
E1:Need good ionizing solvents (usually polar protic solvents)
c)Substrate:
E1 & E2 are both 3o > 2o > 1o(forget methyl) and
E1 is usually not found for 1o
d)Kinetics:
E2:Rate = k[RX][:B-]
E1:Rate = k[RX]
e)Orientation:
E1 and E2 both obey Saytzeff's rule but E2 can have exceptions due to the following:
Stereochemistry:
E2:Need anti coplanar arrangement
E1:No particular geometry is favored.
Rearrangements:
E2:No Rearrangements
E1:Rearrangements are common.
f)Reaction Conditions (Substitution versus Elimination)
Review summary pages & handout distributed in class.
Eliminations are favored at high T and when strong bases are present. E2 is only major one.
D)Some additional points
1)OH -, OR -, and F - are not leaving groups.
2)OH - and OR - can be made into good leaving groups, i.e., HOH and ROH, by using strong acids.
3)One base gives essentially E2 only and that is (CH3)3CO - which only gives SN2 with CH3X. Also it gives the least substituted alkene. For example:
CH3CH2CH(Br)CH3CH3CH2CH=CH2
(not CH3CH=CHCH3)
Chapter 6 Problem Solving Notebook
Assignment 126-30 thru 6-35
Assignment 136-37, 6-38, 6-40, 6-42, 6-43
Assignment 146-45, 6-46, 6-58