Addition Reactions

I. What is Addition?
 New bonds are formed by breaking a ____________________.
 can happen across ___________________________________.

Many have names that

indicate the two groups being
added.

Great synthetic utility. EX: Making polystyrene – the compound that makes up Styrofoam.

Pi bonds can behave as __________________________ or as

____________________________________, making addition
reactions very versatile.

Addition reactions are often the reverse processes of

________________________ reactions.
At equilibrium:
 ___________ temperatures favor
elimination
 ___________ temperatures favor the
addition product

Most addition reactions are carried out _______________ room temperature.

II. Hydrohalogenation
 Results from treating a pi bond with ___________
(where X is Cl, Br, or I).
 _________________ and a _________________
are added across the pi bond.

a. Regioselectivity
When the alkene is ____________________, the halogen can bond at either ____________
position to give the same product. When the alkene is not symmetrical, ________________
must be considered.
Some hydrohalogenations result in the
halogen adding at the ______________
substituted vinylic position.

This is called a ______________________________ addition reaction.

 Has been observed for __________________________________.

Some hydrohalogenations result in the

halogen adding at the _________________
substituted position.

This is called
____________________________addition.
 Proce
eds via radical intermediate
 Not suitable for _____________________

These reactions are ____________________________.

The use of ________________ reagents led to Markovnikov addition while _____________

reagents, especially those contaminated with _________________________________, gave
anti-Markovnikov products.

Example: Predict the major product of each of the following.

a. b.

b. The Markovnikov Hydrohalogenation Mechanism

Hydrohalogenation proceeds via a two

step mechanism:

Commonly observed

Not observed – Less stable

The formation of the ______________ carbocation, which leads to the _______________
substituted product, is thermodynamically favored.

Example: Draw a mechanism for the following transformation

c. Stereochemistry
When a chiral center is formed, a ___________________________________ is produced
 Equally likely to attack from either side

Example: Predict the product(s) of each of the following.

b.
a.

d. Carbocation Rearrangements

Rearrangements will only occur when a

_________________________ carbocation is possible.

The nucleophile will often attack before the

rearrangement can occur, so reactions that can
undergo rearrangement will also produce the
_______________________ products.

These types of reactions are only used for

synthetic purposes with compounds that will not rearrange.

Example: Draw a mechanism for the following transformation:

 e. Hydrohalogenation of Alkynes
Alkynes will undergo a hydrohalogenation reaction
where the halogen bonds to the _______________
substituted carbon.

When treated with_______________,

two addition reactions will happen back
to back, producing the
___________________ dihalide.

The mechanism for this process is the same

two step mechanism we saw for alkenes:

This mechanism proceeds

through the more stable
_____________________ carbocation.

Using HBr that has been contaminated

with _____________________ results in
_____________________ addition and a
mixture of the _____________________
isomers of the product.

We can now convert between

dihalides and alkynes.

Example: Predict the major product for each of the following.

a.
b.

c.
III. Acid-Catalyzed Hydration
Hydration - a reaction in which ___________________________________ is added across a pi bond.
 allow synthesis of ______________________________________________________.

Acid-Catalyzed Hydration – hydration in the presence of an ____________________

 generally proceeds through a _____________________________ pathway.
 acid is not _______________________ during the reaction.
Acids are usually represented as ___________, indicating the
presence of _______________ and an acid.

The catalyst can be specifically identified by

writing its formula in _____________________
over the reaction arrow.

The following representations all indicate an acid-catalyzed hydration:

Adding alkyl substituents around a pi bond will _____________ the rate of

the reaction as it increases the ______________ of the carbocation formed.

a. The Mechanism
This reaction proceeds through a three step mechanism:

The reaction passes through a charged intermediate called __________________________.

 Contains an oxygen atom with a ______________________ charge
 To neutralize this charge, another _______________________________ must occur.

When rearrangments occur, both the ______________

and _____________________________ products form.

Example: Which of the following do you expect to be more reactive toward acid-catalyzed
hydration?

b. Acid-Catalyzed Hydration Equilibrium

Acid-Catalyzed ______________________ - The reverse process of acid-catalyzed hydration
 an ___________ reaction
  at ___________________________ with acid-catalyzed hydration

The equilibrium is sensitive to ___________________ and

__________________________________________.
Addition Elimination

Example: Identify if you should use dilute or concentrated sulfuric acid to complete each of
the following.
a.

b.

c. Stereochemistry
A ___________________ mixture of enantiomers
will form in an acid-catalyzed hydration process
 nucleophile can attack from ___________
_________________ of the carbocation.

Example: Put it all together! Draw the mechanism and predict the product(s) for the
following reaction.

IV. Oxymercuration-Demercuration
Oxymercuration-Demercuration is a two-step process for hydration that avoids the potential for
___________________________________________.

Oxymercuration requires an alkene to react with

mercuric acetate, _____________________,
which will dissociate to form a
___________________________.

 The mercuric cation serves as an __________________

that is attacked by the ______________________.
 The mercury atom will interact with the carbocation to
form a ____________________.
 The resulting structure is known as a _______________.

The mercurinium ion behaves as a hybrid of the two resonance structures

shown above – it has some characteristics of a ____________________ and
some of a _____________________________________.
  Lacks full carbocation character - no ______________ will occur.
 Intermediate is still subject to nucleophilic attack at the
________________ substituted position.
 To achieve a hydration, the nucleophile must be ____________.

Demercuration is used to replace the mercury compound

with a _______________________________.
 Accomplished
using
__________________________________

 Believed to occur through a __________________ process.

Oxymercuration-Demercuration leads to ___________________ hydration without _______________
Example: Predict the product(s) for the following.

V. Hydroboration-Oxidation
To achieve _____________________________ hydration,
hydroboration-oxidation is used.
 This reaction is regioselective and stereospecific.

a. Reagents
______________ must be used in the first step of this reaction.
 fairly ________________ and will react with another
borane molecule to form _________________ which
cannot complete the reaction

_______________________________ is used
as the solvent to stabilize the borane.

b. The Mechanism
* Note: you are not responsible for reproducing this mechanism.

Step 1: Hydroboration

Step 2: Oxidation
c. Regioselectivity
BH2 bonds with the ___________ substituted carbon and is then replaced by an ______
group.
 This can be explained electronically and sterically
i. Electronic considerations
The first step of the hydroboration involves an attack by the
___________________ and a __________________________________.
 The pi bond attacks slightly earlier, forming a
___________________________ charge to which the hydride then shifts.
 The positive charge prefers to be on the _____________ substituted carbon,
causing the boron atom to bond with the ______________ substituted atom.

ii. Steric considerations

The transition state is less crowded, and
therefore less hindered, when BH2 bonds to the
_______________ substituted carbon.

Example: Draw the product you expect for the following.

d. Stereospecificity
Hydroboration-oxidation proceeds via ___________________________ in which the H and
OH must add on ___________________________________ of the pi bond.

_________ chirality centers form - stereochemistry is not considered.

_________ chirality center forms - both

enantiomers are obtained
 syn addition is equally likely to proceed
from either face.
 __________ chirality centers form - both H and OH
are either _________________________________
 must still bond on the same side of the pi
bond.

The other two stereoisomers of the

compound cannot form.

Example: Predict the product(s) of the following.

VI. Hydration of Alkynes

a. Acid-Catalyzed Hydration
Alkynes will undergo acid-catalyzed hydration when
treated with ______________.
 significantly _______________because it must form a
high energy ____________ carbocation intermediate.
 rate can be improved by using __________________
___________________________, as a catalyst.

The initial product of this reaction, an _____________, is not isolated as it quickly converts
to a ________________ through the process of
_______________________________________.

Moves a _________________ and a ______________________.

The ketone and enol are __________________ – _____________________

isomers which rapidly interconvert via the migration of a ______________,
and this specific process is called _________________________________.

The enol formed in the hydration process will be immediately converted into a ketone using
the same ___________________________________ as the main reaction.

Example: Under normal conditions, 1-cyclohexanol cannot be isolated or stored in a bottle

because it undergoes rapid tautomerization to yield cyclohexanone. Draw a mechanism for
this tautomerization.
This process has no __________________
preference - ________________________
alkynes produce a mixture of ketones.

Therefore, this process is only

synthetically used for the hydration of
_____________________ alkynes.

Examples: Predict the major product(s) when each of the following is treated with aqueous
acid in the presence of mercuric sulfate.

b.
a.
b. Hydroboration-Oxidation
Alkynes undergo hydroboration-oxidation,
giving the _____________________ product.

The initial product is an enol that is rapidly tautomerized to an _____________________

through _______________________________________________.

________ BH3 molecules can be added across the _________ pi bonds.

Generally, the __________________ product is desired

 a _________________________________________, such as
disiamylborane or 9-BBN, is used instead of BH 3 to prevent
the second addition.
 these reagents are too ______________________________
to undergo the second addition.

Example: Predict the major product for the following.

 c. Controlling Regiochemistry
Choosing between acid-catalyzed hydration and hydroboration-oxidation can allow us to
choose the ____________________ of our product and therefore choose between
_______________________.

Example: Identify the reagents you would use to achieve the following transformation.
a. b.

VII. Catalytic Hydrogenation

Catalytic Hydrogenation – __________, in the presence of a __________
catalyst, adds across a double bond
 Reduces an alkene to an ___________________

 _____________________ catalysts do not dissolve in the reaction medium

(ex: _________)
_____________________ catalysts dissolve in the reaction medium (ex:
_______________ catalyst)
 Both types of catalysts lead to the same products.
a. Stereospecificity
Catalytic hydrogenation proceeds through a ____________ addition
pathway – both hydrogen atoms bond on the same side of the pi
bond.

1. The hydrogen molecule

interacts with the
surface of the metal,
breaking the
_________________
bond.
2. The alkene coordinates with the surface of the metal, and the pi
bond can react with two hydrogen atoms.

Because both hydrogen atoms add _______________________,

they must be on the same side of the pi bond.

The number of products is

dependent upon the number of
_________________________
formed.

A compound with two chirality centers

may be a _______________ compound.
  _____ product forms rather than a pair of
enantiomers.

Examples: Predict the products of each of the following.

a.
b.

VIII. Reduction of Alkynes

a. Catalytic Hydrogenation
Alkynes can be reduced to _________________ through the
process of catalytic hydrogenation using a ___________________.

 Two equivalents of
_________ are
added to form an
alkane.
 The intermediate ____________________ is difficult to
isolate - it is _________________ reactive toward
hydrogenation than the starting alkyne.

It is possible to isolate the alkene by using a

partially deactivated or ____________________
catalyst such as ________________ catalyst or ________.

A poisoned catalyst will catalyze the first

step, but it will not lower the
_____________ for the second
hydrogenation.
 Always produces the __________ alkene –
both hydrogen atoms must bond to the
___________ ________________ of the
bond because they are coordinated to the
same metal complex.

Example: Predict the major product expected from the following reaction:

b. Dissolving Metal Reduction

Alkynes can be reduced to ___________ alkenes
through dissolving metal reduction.
 When dissolved in ammonia, sodium will behave as a
source of electrons. This reaction must be carried out at
very ____________ temperatures because ammonia has
a low ________________ (-33 °C).

This is a four-step mechanism:

The first step of the mechanism produces a ____________________________

intermediate as ____________ electron is transferred from the sodium to the alkyne.

____________________ show the movement of single electrons, as shown in step 1.

This intermediate is responsible for the ___________ outcome

of the reaction. The energy of the radical anion is __________
when the nonbonding electrons are as far apart as possible.

Example: Predict the major product when the following is treated with sodium in liquid
ammonia.

c. Choosing a Reduction Method

Example: Identify the reagents you would use to achieve each of the following.

IX. Halogenation and Halohydrin Formation

a. Halogenation
Halogenation is the addition of _________________ across a pi bond.
 Fluorine reacts too ___________________
 Iodine gives very _____________ yield.

The chlorination of ethylene is a major step in the production of _______________:

Halogenation is ____________________ - proceeds primarily
via _________________________________.
 the two halogen atoms are placed on ____________
______________ of the pi bond.

When a nucleophile approaches a bromine molecule, it

induces a ___________________ in the normally
nonpolar compound.

When an alkene attacks a bromine molecule, it forms a bridged intermediate called a

______________________ ion. This ion is then attacked by the remaining bromide ion
through an ______________ process.

The SN2 requirement for a _____________________ attack leads to the anti-addition

products.

Alkynes react in the same way as alkenes for halogenation.

 because they have two pi bonds, __________________
of the halogen can be added
 alkyne halogenations are carried out in _____________
It is possible to add only _____________ of halogen
across an alkyne.
 proceeds via
___________________________ and yields the
______________________ as the major product.

Example: Predict the major product(s) for of the following.

Example: What reagents would you use to complete the following transformation?

b. Halohydrin Formation
 Bromination is generally carried out in a non-nucleophilic solvent such as
_________________. When it occurs in ___________________ instead, the nucleophilic
attack can be carried out by the water rather than bromide, producing
______________________.

When chlorine is used rather than bromine, a

______________________________ is produced.

Halohydrin formation is a _________________________

process in which the OH group bonds to the
_______________ substituted position.

As the water attacks, the ________________________ shifts from the

bromine to the water by passing through a carbon atom.
 The ___________________ substituted carbon is more capable of
stabilizing this charge

Example: Predict the major product(s) of the following reaction.

X. Anti Dihydroxylation
Dihydroxylation involves the addition of ________________
groups across a double bond.
 Anti dihydroxylation - OH groups add on ______________
____________ of the bond, resulting in a ______________________.

A three membered cyclic ether, known as an _____________________, is formed as an

intermediate between the first and second steps.
Step 1: Epoxide formation
 Step 2: Acid-catalyzed epoxide opening

The first step of the reaction requires a ____________________ (RCO3H).

An ________________ environment is used to protonate the epoxide

 produces a ______________________ similar to the
bromonium ion and mercurinium ions
 the protonated epoxide must be attacked from the _______
____________, resulting in the ________________ product.

Examples: Predict the major product(s) for each of the following.

a. b.

XI. Syn Dihydroxylation

Syn dihydroxylation - OH groups add on _____________________
of the bond, resulting in a _________________________.
 An alkene is treated with _____________________________
to produce a cyclic ___________________________.
 Because both oxygen atoms bond simultaneously, the syn
product is formed.

Treatment with sodium sulfite ________________ or sodium

bisulfite _________________, gives the resulting
_______________.
 Not preferred – OsO4 is expensive and toxic

A similar mechanism occurs by reacting the alkene

with cold ________________ in _______________.
 frequently leads to further _____________
of the diol as KMnO4 is a very strong
oxidant.

Examples: Predict the product(s) of each of the following reactions.

a. b.
XII. Ozonolysis
Treatment with _______________ breaks the carbon-carbon pi
bonds to form ___________________ double bonds.
 Ozone reacts with the alkene to produce an ______________________ that rearranges to become
more stable.

Treatment with a ___________________ agent, such as

_________________, gives the carbonyl products.

Example: Predict the products when the following

compound is treated with ozone followed by DMS.

Example: Identify the structure of the starting alkene.

Alkynes must be treated with ozone followed by ______________

to produce _________________________________.

When the reactant is a terminal alkyne, the terminal side

becomes _________________________.

Oxidative cleavage can be used to determine the ______________________ of an unknown alkyne.

Example: Predict the major product(s) when each of the following is treated with ozone followed by
water.

a.
b.
XIII. Alkylation of Terminal Alkynes
Terminal alkynes can be deprotonated to produce
______________ using a _____________________________
such as NaNH2.

When alkynide ion is reacted with a ___________________

alkyl halide, the alkyl group is added; this process is called
alkylation.
 ______________
_________________ alkyl halides cannot be used - would
yield the elimination products.

Acetylene can be converted into any simple _______________ through two successive alkylation
steps.
 must be done in two steps - having NaNH 2 and RX in the flask at the same time would give
unwanted _______________________________________________ products.

Example: Identify the reagents necessary to convert acetylene into 7-methyl-3-octyne.

XIV. Putting it all together - Predicting Addition Products
When approaching an addition problem, three factors must be considered.
1. What ____________________ will I be adding?
2. Will the process be __________________________ or ___________________________?
3. What is the ______________________________ (syn or anti)?

Example: Predict the products of the following reactions.

a.

b.

XV. Synthetic Strategies

So far, we have discussed three different processes: substitution, elimination, and addition.

Substitution reactions allow us to ____________________ one

group with another.

Elimination reactions allow us to ______________ halogens or OH groups

to give an _________________.

Addition reactions allow us to ____________ two groups across a

_______________________.

To generate more complex synthetic pathways, we must understand these simpler pathways
individually.

a. Changing the Position of a Leaving Group

Moving a leaving group is accomplished using
__________________ followed by ______________.

For elimination: Do we need Zaitsev or Hofmann?

Choose reagents accordingly
 Zaitsev - _______________ base (ex: sodium
methoxide)
 Hofmann – _______________________ base
(ex: t-buOK)
 E2 reactions are preferred for better control
over ____________________________.

The ___________________________ of the addition step can be controlled using the methods we
have discussed in this unit.
EX: _______________ can be used to give a Markovnikov product while ____________________
will give the anti-Markovnikov product.
When OH is the leaving group, it must first be converted to a good leaving group using
_____________ _________________________ to allow the reaction to proceed via an
_______________ pathway.

Examples: Identify the reagents you would use to accomplish each of the following transformations.

a.

b.

c.

b. Changing the Position of a Pi Bond

To change the position of a pi bond, use an ___________
followed by an ______________________.
 control the regiochemistry of this reaction in the
same way to ensure synthesis of the desired
product.

Examples: Identify the reagents you would use to accomplish each of the following transformations.
a.

b.

c. Synthesis with Alkynes

Examples: Propose efficient synthetic pathways for each of the following.

a.

b.

c.

Summary – Addition to Alkenes

Groups Rearrangement
Reaction Type Reagents Regio Stereo
Added Possible?
Hydrohalogenation HX H&X Yes Markovnikov N/A
Anti-
Hydrohalogenation HBr, ROOR H & Br No N/A
Markovnikov
Acid-Catalyzed
H3O+ H & OH Yes Markovnikov N/A
Hydration
Oxymercuration- 1)Hg(OAc)2, H2O
H & OH No Markovnikov N/A
Demercuration 2) NaBH4
Hydroboration- 1) BH3 • THF Anti-
H & OH No Syn
Oxidation 2) H2O2, NaOH Markovnikov
Catalytic
H2, metal cat. H&H No N/A Syn
Hydrogenation
Halogenation X2 (X = Br or Cl) X&X No N/A Anti
Halohydrin Formation X2, H2O X & OH No Markovnikov Anti
1) RCO3H
Anti-Dihydroxylation OH & OH No N/A Anti
2) H3O+
KMnO4, NaOH,
cold
Syn-Dihydroxylation OR OH & OH No N/A Syn
1) OsO4
2) NaHSO3, H2O
1) O3 O&O
Ozonolysis No N/A N/A
2) DMS (carbonyl)