Download Learning Guide for Chapter 9 - Alkyl Halides I

Learning Guide for Chapter 9 - Alkyl Halides I
I. Introduction to alkyl halides
types of organic halides, where alkyl halides are found, preparation,
spectroscopy, reactivity, nomenclature
II. Substitution reactions of alkyl halides
Introduction
Mechanisms
Which substitution reaction?
Strong vs Weak Nucleophiles
Products
Stereochemistry
Rate Laws
Rearrangements
Solvents
Exclusion of aryl halides, vinyl halides, and acid chlorides
Summary of Substitution Reactions
III. Synthesis Using Substitution Reactions
I. Introduction to alkyl halides
Types of organic halides
What is the purpose of categorizing organic halides into different groups?
so that we can predict how they will react
Label the following compounds as alkyl halides, aryl halides, and acid halides.
O
Cl
Cl
Cl
Ch 9
aryl halides
Ch 16
acid halide
Ch 22
alkyl halide
This chapter will focus on: alkyl halides
Compounds with more than one halide can be classified by how close together the halides
are. Which of these is a geminal dihalide, and which is a vicinal dihalide?
these are special kinds of dihalides
Cl
Cl
Cl
geminal dihalide
halides on the same C
vicinal dihalide
Cl
halides on neighboring C's
LG Ch 9 p 2
Not all compounds that contain a benzene ring are aryl halides. Classify the following.
What category do they all belong to?
sp2
sp3
I
sp3
Br
Cl
benzyl halide
aromatic
one C away
aryl halide
aromatic
directly attached
NOT an alkyl halide
aromatic
more than one C away
alkyl halide
alkyl halide
Organic halides may also contain a C=C. Classify the following. What category do they
all belong to?
sp3
sp3
Cl
Br
Br
sp2
allyl halide
unsaturated
one C away
vinyl halide
unsaturated
directly attached
unsaturated
more than one C away
alkyl halide
alkyl halide
NOT an alkyl halide
Some aromatic halides and some unsaturated halides react like are alkyl halides, and some
do not. The important factor is the hybridization of the C the halogen is attached to.
sp3 carbon alkyl halide benzyl, allyl, other aromatic
sp2 carbon NOT an alkyl halide aryl, vinyl
Label the following as methyl, 1o, 2o, 3o, allyl, and benzyl.
Cl
H
H
3o
Cl
H
Br
Cl
Cl
I
Br
Cl
Br
2o
2o, allylic
1o
2o
methyl
Br
1o
3o
2o, benzylic
3o
LG Ch 9 p 3
Where organic halides are found
no
Are organic halides common in nature?
Why is iodine necessary in the human diet? to make thyroid hormone
Where do we get it?
I
iodized salt
What happens if you don't? goiter
I
HO
H2N
O
O
I
OH
I
How are alkyl halides used in industrial, commercial, and medical applications?
H3C
Cl
C Cl
Cl
Cl
C
H
dichloromethane
(or methylene chloride)
solvent
H
F
F
Br
C
C
F
H
Cl
refrigerant
F
Halothane
anesthetic
Cl
Freon-12
Cl
CF3CHClBr
Cl Cl
Cl
F
C
C
H
CHCl3
chloroform
solvent, old anesthetic
Cl
Cl
Cl
dry cleaning fluid
Cl
CH2Cl2
Cl
1,1,1-trichloroethane
Cl
chlordane
pesticide
Cl
Cl
Cl
Preparation of alkyl halides
How can alkyl halides be synthesized from alkanes? halogenation
What difficulty does this reaction have?
forms multiple products; can be separated by fractional distillation, not practical in
the lab
What kind of intermediate is formed in this reaction? radical
H
H
Cl
Cl
h!
Cl
or heat
C
H
H
H
H
C
H
Cl
+
H
Cl
H
Cl
H
C
H
Cl
+
Cl
LG Ch 9 p 4
What would the products of the following reaction be?
Cl
Cl
excess Cl2
Cl
h! or heat
+
+
Cl
Cl
Cl
+
etc
does this look practical?
What reagent can be used in place of Br2?
NBS
What stabilitzes radical intermediates?
3o > 2o > 1o
resonance (allyl, benzyl)
Why are the following reactions successful at forming only one major product?
Cl
Cl2
h!
Cl2
all carbons are the same,
only one monosubstituted
3o radical is much more
stable than 1o radicals
Cl
or
h!
Cl
NBS
h!
allylic radical
is more stable
because is has
resonance
Spectroscopy of alkyl halides
What IR bands does this alkyl halide spectrum have?
C-H stretching
3000-2850 cm-1
CH3 & CH2 bending
1460, 1380 cm-1
Is IR a good way to identify alkyl halides?
C-X
800-500 cm-1
nope - they look like alkanes
LG Ch 9 p 5
How can you locate the H's on a C with a halogen attached? chemical shift: 3-4 ppm
Assign the H's on the following spectrum.
Br
Reactivity of alkyl halides
Give the order of electronegativity of halogens atoms: F > Cl > Br > I
Give the order of size of the halogen atoms:
Give the order of bond strength of C-X:
I > Br > Cl > F
C-F > C-Cl > C-Br > C-I
not reactive
reactive
!+!-
Show the polarity of the carbon-halogen bond:
Cl
Show how an alkyl halide can react in each of the following ways:
arrows?
dissociation:
products?
+
Cl
this one will react further
Cl
Nu
displacement:
Cl
Nu
what kind of reagent?
acid/base:
Cl
H
H
Base
+
Cl
these two are done
products?
+
Cl
+
H-base
what kind of reagent?
where are the acidic H's?
What do all of these reactions have in common?
break C-X bond, have X- product
LG Ch 9 p 6
Nomenclature of alkyl halides
What are the two ways to name alkyl halides?
IUPAC (systematic names) - using the normal rules
common names - only works for simple alkyl halides
How do you construct a common name?
name of alkyl substituent + name of halide
Give the common names for the following compounds.
Br
propyl bromide
sec-butyl fluoride
F
isopropyl bromide
Cl
Cl
vinyl chloride
Cl
I
allyl iodide
cyclobutyl bromide
Br
benzyl chloride
Br
phenyl
bromobenzene
Why can't you write a common name for the following compound?
there is no name for this substituent
Cl
Review the steps for naming a compound using IUPAC rules.
1) choose the main chain or ring 1st priority - longest
2nd priority - most subst
1st priority - first subst, then 2nd, etc
2nd priority - alphabet
3) name and order substituents
2) number the chain or ring
4) add stereochemistry, if needed
LG Ch 9 p 7
Give names for the following compounds.
Br
compare to common name
Cl
bromocyclopentane
(common name: cyclopentyl bromide)
3-chloro-2-methylpentane
I
Br
this is a geminal dihalide
but that isn't part of its name
Br
3,3-dibromopentane
(R)-3-iodohexane
Br
Cl
2-bromoethylcyclohexane
2-chloro-3-ethyl-4-methylhexane
II. Substitution reactions of alkyl halides
Introduction
What are the two types of reactions that alkyl halides can do?
substitution and elimination
Which of the reactions represented below is a substitution reaction? Which is an
elimination reaction? Why?
Cl
+
O
Na
+
O
Na
Cl
Nu
E
ethoxy
Substitution - the ethoxy group takes the place of the chloride
Br
+
O
K
+
OH
+
K
Br
H
acid
base
Elimination - the bromide and a hydrogen are removed from the alkyl halide, (one
ends up on the base, the other alone) leaving behind a C=C
Which of these will we study in this chapter? In the next?
Ch 9 - substitution
Ch 10 - elimination
LG Ch 9 p 8
Mechanisms
What is a mechanism?
shows the movement of electrons in each step of the reaction
How many ways can a substitution occur? What are the mechanisms called?
2 ways - SN1 and SN2
Nu
E
SN2:
Cl
Na
O
O
+
Na
Cl
attack-push off
What type of Lewis acid/base reaction is this?
displacement
How could this mechanism be described? attack-push off
Where is the nucleophile, and where is the electrophile?
Why is the alkyl halide a good electrophile?
the C is partially +
the Cl can come off
Why is the alkoxide a good nucleophile? O is -, becomes neutral
SN1:
acid
Nu
E
O
Cl
fall off
+
Cl
H
H
O
O
H
deprotonate
attack
What type of reaction is this?
base
O
+
dissociation, association, acid/base
How could this mechanism be described? fall off, attack, deprotonate
Where are the nucleophile, electrophile, acid, and base?
Why can alkyl halides dissociate?
bond is polar
Cl can come off
Why is the carbocation a good electrophile?
incomplete octet, needs a bond
H
O
H
LG Ch 9 p 9
Which substitution reaction?
How are the SN1 and SN2 reactions the same?
both involve reaction with a Nu
same net result - substitution
Which are the two electrophiles used in the examples? Which do you think is more
reactive? Why?
SN2
SN1
incomplete octet
complete octet,
full + charge
only partial + and less reactive
more reactive
Cl
What are the two nucleophiles used in the examples? Which do you think is stronger, and
why?
SN2
SN1
O
stronger - negatively charged
O
H
weaker - neutral
How do the strength of the nucleophile and electrophile fit together?
SN2: strong Nu, weak E
SN1: weak Nu, strong E
Scenario A: strong Nu added to alkyl halide
Nu attacks! SN2
Scenario B: weak Nu added to alkyl halide
Nu can't attack, sits around waiting until alkyl halide dissociates, then
attacks carbocation - SN1
What determines whether an SN1 or and SN2 reaction will occur?
the strength of the nucleophile
Following the pattern of the reactions given previously, draw the mechanisms for the
following reactions:
SN2
Br
Na
C
N
(strong Nu)
SN1
Br
H
O
H
(weak Nu)
LG Ch 9 p 10
Nucleophiles in Substitution Reactions
The following are nucleophiles commonly used in substitution reactions, listed in order of
nucleophilicity:
alkyne anions
cyanide
N
RC
C
C
thiolates
R
S
hydroxide
H
O
alkoxides
R
O
strong Nu - SN2
exception:
tert-butoxide
halides
water
Cl
H
alcohols
Br
O
R
O
I
H
OH
weak Nu - SN1
exception:
tert-butyl alcohol
OH
What is the cut off point between nucleophiles that follow SN2 vs. SN1 mechanisms?
Why is are alcohols weak nucleophiles while alkoxides are strong nucleophiles?
charge:
alkoxides - negative charge
alcohols - neutral
Why won't tert-butoxide and tert-butyl alcohol work as nucleophiles?
steric hindrance - tert-butyl is too big to attack C
Why are alkyne anions the best nucleophiles?
C is the least EN
Which of the halides is the best nucleophile? Why are they all poor nucleophiles?
all EN
I- biggest
LG Ch 9 p 11
Products
Give the products of the following reactions. Then note what nucleophile produced what
product. Which mechanism will each follow?
SN2
Br
+
Na
acetylide - alkynes
+
Br
SN2
C
Na
N
N
cyanide - nitriles
SN2
+
Br
O
Na
H
OH
hydroxide - alcohols
SN1
+
Br
H
O
OH
H
water - alcohols
SN2
Br
+
O
O
Na
alkoxides - ethers
SN1
Br
OH
+
O
alcohols - ethers
SN2
Br
+
S
S
Na
thiolate ions - sulfides
SN2
Br
+
Na
I
I
halides - alkyl halides
LG Ch 9 p 12
Stereochemistry
Can a substitution reaction involve a carbon that is a stereocenter? yes
Can a substitution reaction create a new stereocenter? no
What happens to a stereocenter involved in an SN2 reaction?
Cl
NaOH
inverted
OH
MODELS
How does this happen?
in order to push halide off, Nu must come from behind
Cl
Cl
Cl
H
H
OH
HO
HO
tetrahedral
trigonal bipyramid
tetrahedral
What happens to a stereocenter involved in an SN1 reaction?
Cl
H2O
OH
racemized
OH
+
How does this happen?
when the C+ is formed, the Nu can attack from either side
Cl
H
chiral
OH2
OH
H
H
OH2
OH
H
achiral
The actual ratio isn't 1 to 1 - it's more like 2 to 3. Why?
the departing Cl partly blocks one side
LG Ch 9 p 13
Rate laws
Consider the following SN2 reaction.
Na
O
O
Cl
Na
Cl
Draw the energy diagram for this reaction.
Which reagents are involved in the rate limiting step?
alkyl halide and nucleophile
Draw the structure of the transition state.
Cl
H
H
O
What would happen if you
doubled the concentration of the alkyl halide? rate would double
doubled the concentration of the nucleophile?
rate would double
What is the order of the alkyl halide? the nucleophile? 1st order in both
Write the write law:
rate = k[RX][Nu]
What does SN2 stand for?
Substitution Nucleophilic 2nd order
What happens to the rate of SN2 reactions as the substitution increases?
MODELS
steric
hindrance
methyl
2o
1o
3o
Cl
CH3Cl
Cl
none
a little
some
fast
fast
slower
Cl
a lot
activation
energy
rate of
reaction
no reaction
LG Ch 9 p 14
Consider the following SN1 reaction.
OH
+
O
Cl
OH2
Cl
Draw the energy diagram for this reaction.
Which is the rate limiting step?
fall off - creating a C+
Cl
Draw the structure of the transition state for this step.
Which reagents are involved in the rate limiting step?
only the alkyl halide
What would happen if you
doubled the concentration of the alkyl halide? rate would double
doubled the concentration of the nucleophile or base? nothing!
What order is the alkyl halide? the nucleophile or base?
Nu 0th order
Write the write law: rate = k[RX]
What does SN1 stand for?
alkyl halide 1st order
Substitution Nucleophilic 1st order
What happens to the rate of SN1 reactions as the substitution increases?
MODELS
carbocation
stability
methyl
2o
1o
3o
Cl
Cl
CH3Cl
Cl
none
a little
some
a lot
no reaction
no reaction
slower
fast
activation
energy
rate of
reaction
LG Ch 9 p 15
How does the identity of the halogen atom affect the rate of substitution reactions?
two possible explanations:
* longer bonds break more easily
RI fastest
which is more important?
more EN, more stable afterwards RF fastest
CH3I
>
CH3Br
>
CH3Cl
>>
CH3F
too slow
Will this be true for both SN2 and SN1 reactions?
yes - C-X breaks in rate-limiting step
Rearrangements
In which substitution reaction do carbocations form?
SN1
whenever a carbocation is formed, draw it out and look for rearrangements!
Why do carbocations undergo rearrangements?
in order to become more stable
Which carbocations are mostly likely to rearrange?
2o - want to become 3o
What are the two ways in which a carbocation can rearrange?
hydride shift, alkyl shift
Which carbocation will give the product?
both!
Give the substitution products in the following reaction.
Br
H2O
OH
OH
LG Ch 9 p 16
Solvents
Why is a solvent useful when running a reaction?
dissolve the reagents
(you don't have to write the solvent, but you
usually have to use one!)
can affect the reaction rate
What are the important issues when considering solvents for substitution and elimination
reactions?
1) polarity
van der Waals - non polar
dipole forces - moderate to highly polar
hydrogen bonding - highly polar
2) hydrogen bonding yes - protic
no - aprotic
What kind of solvent do SN2 reactions require?
high polarity solvent - to dissolve charged reagents
aprotic solvent - hydrogen bonding slows down the reaction
surrounds Nu/base, makes it hard to react
What kind of solvent do SN1 reactions require?
polarity isn't important - reagents are not charged, dissolve easily
protic solvent - stabilizes the C+, increases reaction rate
What solvents are in the following categories?
nonpolar
hexane, toluene
moderately polar
no good - won't dissolve charged reagents
can't stabilize C+
ethyl acetate, dichloromethane, diethyl ether
highly polar, aprotic
acetone, N,N-dimethylformamide, acetonitrile
O
O
CH3
H
highly polar, protic
not very good
alcohols, water
N
C
N
good for SN2, E2
good for SN1, E1 - usually = Nu/base
LG Ch 9 p 17
Exclusion of aryl halides, vinyl halides, and acid chlorides
Why can't aryl halides undergo substitution reactions?
Cl
NaOH
Cl
H2O
no rxn - C+ is too unstable
O
Cl
no rxn - pi bonds block Nu from attacking
vinyl halides, acid chlorides have similar reasons
Cl
Summary of Substitution Reactions
SN2 reactions:
SN1 reactions:
result: halide replaced by Nu
result: halide replaced by Nu
(usually minus its H)
mechanism: 1 step
mechanism: 3 steps
attack-push off
fall off
attack
deprotonate
reagent: strong nucleophile
reagent: weak nucleophile (also a base at
the end, use as solvent)
stereochemistry: inversion
stereochemistry: racemization
rate law: rate = k[RX][Nu]
rate law: rate = k[RX]
alkyl halides: methyl >1o > 2o >> 3o
alkyl halides: 3o > 2o >> 1o >methyl
RI > RBr > RCl >> RF
RI > RBr > RCl >> RF
rearrengements? no
rearrengements? yes
solvent: polar, aprotic
solvent: polar, protic (usually Nu)
LG Ch 9 p 18
III. Synthesis Using Substution Reactions
What is synthesis?
figuring out how to make a compound
each reaction you learn will be a tool in your toolbox to make a specific change
substitution - alkyl halide to other functional groups
What steps should you go through?
1) look at the compound to decide what nucleophiles you could use
2) decide what alkyl halides you could use
3) decide if the reaction will be favorable
Consider the following target molecules:
nucleophile
N
Na
C
NaCN
strong
N
Br
N
rxn
favorable?
SN2
yes
SN2
no - slow
1o
Cl
NaCN
strong
N
alkyl halide
2o
NaCN
Cl
strong
no
SN2
too bulky
SN2
no
3o
N
NaCN
Br
strong
aryl
aryl halides
don't do SN2
LG Ch 9 p 19
alkyl halide
nucleophile
OH
rxn
* NaOH strong
or
NaOH strong
SN2
yes
SN1
no
C+ can't form
Br
1o
H2O weak
OH
favorable?
Br
SN2
no
slow
2o
SN1
no
slow
or
H2O weak
OH
NaOH strong
Br
no
too bulky
SN1
yes
3o
or
* H2O weak
NaOH strong
OH
SN2
Br
SN2
aryl
SN1
no
C+ can't form
or
H2O weak
strong
strong
Br
Br
CH3Br
Br
no
C+ can't form
2o
SN2
no
slow
1o
SN2
yes
SN2
yes
SN2
no
C+ can't form