REACTIONS AND SYNTHESIS Alkenes undergo many addition ...
CHAPTER 7 - ALKENES: REACTIONS AND SYNTHESIS Alkenes undergo many addition reactions. We have seen one - addition of HX (Markovnikov's Rule). H C
X C X
Halide
X C
C
C
C
1,2-Dihalide
OH C H
Halohydrin
H C O C
H C
Alkane
C
OH C
C
Alcohol
HO C
OH C
1,2-Diol
C O Epoxide
X C
Carbonyl
Reactions of alkenes are usually addition reactions. Preparations of alkenes are eliminations. Addition C
C
A C
B C
Elimination
Preparations of Alkenes: Alkenes are generally prepared by elimination reactions. The two most common are dehydrohalogenation (loss of H-X from an alkyl halide) or dehydration (removal of water from an alcohol). The mechanism for these reactions will not be covered until chapter 11.
H Br H H
KOH EtOH
H H
Dehydrohalogenation is carried out in strong base such as potassium hydroxide. Remember how reactions can be written. In the above case the reagent is above the arrow and the solvent, ethanol, is below the arrow. H OH H H
H2SO4 (aq) THF,50˚C
H H
Dehydration is carried out in strong aqueous base. THF is tetrahydrofuran, an often used solvent.
Addition Reactions: 1. Halogens Bromine and chlorine add to alkenes yielding 1,2-dihaloalkanes. In fact the addition of Br2 is used as a visual test of unsaturation. Br2 is a reddish liquid and immediate disappearance of the color indicates a double bond. Fluorine is too reactive and iodine does not react. Below are examples H H
H C
C H
Cl2
Cl C
Cl C
Addition of chlorine to ethylene
H H
H Br2
Br Br H
Addition of bromine to cyclohexene
A mechanism can be proposed that is similar to the addition of H-X to alkenes. H
d+
d-
Br
Br
H Br
H
-
Br Br H
Br H
H
However when products of cycloalkene are examined, it is found that only trans 1,2-dibromo products are formed. If intermediate is as shown above, Br- can come in from either side of the ring and both cis and tans isomers should be formed Empty p orb.
H
Br
C
Br
Suggests that intermediate is not a carbocation but a bromonium ion. Br H H
-
H
H
Br
H Br
Br
Br +
This is called a reaction with anti-stereochemistry.
Br
H
2. Halohydrin Addition of the elements of HO-Br or HO-Cl to the alkene. Don't use these as reagents but rather Cl2/H2O or Br2/H2O. X
X2 H2O
HO
Initially Br2 reacts with the alkene to form the bromonium ion. In the presence of an additional nucleophile, the new nucleophile can attack the bromonium ion and get a different product.
Adds according to Markovnikov's rule based on stable carbocations. OH2 H H
H
H H
H
O
Base
H
OH
H Br
Br
Br +
Br
H
Br
H
Show examples
N-Bromosuccinimide, NBS, is often used as a source of bromine since it is easier to handle than liquid Br2.
3. Hydration of Alkenes - Oxymercuration
Water can be added to alkene in process called hydration. Rection takes place with water and a strong acid catalyst.
H3C
H H A
H3C
H
H3C
H
H3C
H
OH2
H
H H O H H3C H CH3 H
Base
OH H H3C
H CH3 H
Note the deprotonation step at the end. Industrially ethanol is prepared from ethylene with H2O and phosphoric acid at 250˚C. In the laboratory the procedure is modified into what is called oxymercuration. CH3
1.Hg(OAc)2 , H2 O/THF
CH3
2. NaBH4
OH
The process is a two-reaction sequence. The numbers indicate that each of the steps is carried out separately. This is different than showning steps in a mechanism for a single particular reaction. If two separate reactions are carried out, this must be clearly indicated.
The first part of the reaction is analogous to halohydrin formation with the electrophilic addition of mercuric ion to the alkene to form a mercurinium ion and then water comes in. The separate second step in the sequence is a reduction reaction to break the organomercury bond to give the alkane.
Hg+
OAc Hg
CH3
OAc
HgOAc CH3
OAc CH3
CH3
O H
OH2
H -
OAc
HgOAc CH3
2.NaBH4
OH
OH
This reaction follows Markovnikvo's rule - formation of most stable carbocation.
4. Hydration of Alkenes - Hydroboration Borane, BH3, adds to double bonds C
C
+ H
H B
H
BH2
H
This is a tri hydride and all three hydrides add to form a trialkyl borane CH2CH3 CH2=CH 2 + BH 3
CH3CH2
B CH2CH3
The reaction is useful because the trialkyl borane when treated with aqueous hydrogen peroxide in basic solution yields alcohols. The overall reaction adds the elements of H-OH in an anti-Markovnikov fashion (regio chemistry) and in a syn (or same side) stereochemistry CH2CH3 CH2=CH 2 + BH 3
CH3CH2
B CH2CH3 H2O2, H2O OH
3 CH3CH2OH
The following reaction shows the anti-Markovnikov regio chemistry of the reaction H
H3C
H BH3
H2O 2,HO
OH
--
H3C
H2O
H
NOTE: The reaction arrow may be written: 1. BH3 2.
H2 O2 , HO--, H2 O
It is a TWO REACTION sequence.
Unlike other additions, the addition of borane to alkenes is a single step reaction. The dotted lines indicate bonds being made and broken simultaneously. H H H3C
B +
H
H H3C
d- H B H
d+
SYN addition
Both steric and electronic arguments predict the regiochemistry, but steric influences are probably most important.
During the oxidation step (B-C bond replaced by C-OH) the boron is replaced by OH with the same stereochemistry so the overall addition is syn, nonMarkovnoikov.
5. Carbenes: Formation of Cyclopropanes Divalent carbon compounds are usually too unstable to isolate & often too reactive to be of much synthetic use (react too indiscriminately). Two exceptions are illustrated below. Cl
Cl C
+
:CCl2
KOH/H2O
CHCl3
Dichlorocarbene can be prepared readily from chloroform and KOH. This divalent carbon species reacts with double bonds stereospecifically to give the corresponding cyclopropanes.
H H3C
Cl
KOH / CHCl3
H CH2CH3
H2O - EtOH
Cl C
H
H
H3C
CH2CH3
Stereospecific: syn-addition
Dichlorocarbene can be viewed as a “neutral carbocation,” that is sp2 hybridized:
Empty p-orbital Cl
:CCl2
Filled sp2 orbital
Cl
Dichlorocarbene
A useful way to make cyclopropanes themselves is by the Simmons-Smith reaction where activated zinc (so-called zinc-copper couple) pulls the two I’s from diiodomethane to give a reactive intermediate that behaves as if it were :CH2 & that reacts nicely with alkenes to give cyclopropanes. CH3 H3C
CH3 CH2I2 - Zn(Cu) Et2O
H3C
H H
Simmons-Smith Rxn: CH2I2 + Zn(Cu)
Note that sterics plays a role in directing the incoming reactant to the less hindered face of the double bond.
5. Hydrogenation of Alkenes - Reduction Addition of H-H
+
H
H
Catalyst
H
H
Platinum and palladium are the usually employed catalysts - Pt in the form of PtO2 and Pd on charcoal written Pd/C. Ususally occurs with syn hydrogenation - both hydrogens add to the same side of the double bond. CH3
CH3 H2, PtO2 acetic acid
CH3
H H
H H CH3
C C
Very sensitive to steric hindrance in some molecules.
H H
C C
Alkenes are more reactive to hydrogenation than other groups with double bonds such as the carbonyl groups. So reaction is selective. O
O H2, Pd/c ethanol
6. Hydroxylation Hydroxylation of an alkene is the addition of an -OH group to each of the carbons in the double bond. It is essentially an oxidation reaction. The intermediate in the reaction is a cyclic osmate that is cleaved in a second step with aqueous sodium bisulfite
hydroxylation
Overall reaction
C
C C OH OH H
H H
C
H O
OsO4
NaHSO3 H2O
O Os
Pyridine (Py)
O
O
H
H
8. Oxidative Cleavage a. Ozonolysis C
C
O3
Zn HOAc/H2 O
C
O
+
O
C
Aldehydes and ketones
In the presence of Zn in the second step, the products are limited to aldehydes and ketones. This reaction can be used as an analytical too. Show examples
OH OH
b. KMnO4 is neutral or acidic media cleaves the C=C R
C H
CH2
O
KMnO4
R
H3O+
C OH
O R C H R R C H2C
Show examples
R
C
acids OH
R R
C O
Ketone
CO2 carbon dioxide
X C X
Halide
X C
C
C
C
1,2-Dihalide
OH C H
Halohydrin
H C O C
H C
Alkane
C
OH C
C
Alcohol
HO C
OH C
1,2-Diol
C O Epoxide
X C
Carbonyl
Reactions of alkenes are usually addition reactions. Preparations of alkenes are eliminations. Addition C
C
A C
B C
Elimination
Preparations of Alkenes: Alkenes are generally prepared by elimination reactions. The two most common are dehydrohalogenation (loss of H-X from an alkyl halide) or dehydration (removal of water from an alcohol). The mechanism for these reactions will not be covered until chapter 11.
H Br H H
KOH EtOH
H H
Dehydrohalogenation is carried out in strong base such as potassium hydroxide. Remember how reactions can be written. In the above case the reagent is above the arrow and the solvent, ethanol, is below the arrow. H OH H H
H2SO4 (aq) THF,50˚C
H H
Dehydration is carried out in strong aqueous base. THF is tetrahydrofuran, an often used solvent.
Addition Reactions: 1. Halogens Bromine and chlorine add to alkenes yielding 1,2-dihaloalkanes. In fact the addition of Br2 is used as a visual test of unsaturation. Br2 is a reddish liquid and immediate disappearance of the color indicates a double bond. Fluorine is too reactive and iodine does not react. Below are examples H H
H C
C H
Cl2
Cl C
Cl C
Addition of chlorine to ethylene
H H
H Br2
Br Br H
Addition of bromine to cyclohexene
A mechanism can be proposed that is similar to the addition of H-X to alkenes. H
d+
d-
Br
Br
H Br
H
-
Br Br H
Br H
H
However when products of cycloalkene are examined, it is found that only trans 1,2-dibromo products are formed. If intermediate is as shown above, Br- can come in from either side of the ring and both cis and tans isomers should be formed Empty p orb.
H
Br
C
Br
Suggests that intermediate is not a carbocation but a bromonium ion. Br H H
-
H
H
Br
H Br
Br
Br +
This is called a reaction with anti-stereochemistry.
Br
H
2. Halohydrin Addition of the elements of HO-Br or HO-Cl to the alkene. Don't use these as reagents but rather Cl2/H2O or Br2/H2O. X
X2 H2O
HO
Initially Br2 reacts with the alkene to form the bromonium ion. In the presence of an additional nucleophile, the new nucleophile can attack the bromonium ion and get a different product.
Adds according to Markovnikov's rule based on stable carbocations. OH2 H H
H
H H
H
O
Base
H
OH
H Br
Br
Br +
Br
H
Br
H
Show examples
N-Bromosuccinimide, NBS, is often used as a source of bromine since it is easier to handle than liquid Br2.
3. Hydration of Alkenes - Oxymercuration
Water can be added to alkene in process called hydration. Rection takes place with water and a strong acid catalyst.
H3C
H H A
H3C
H
H3C
H
H3C
H
OH2
H
H H O H H3C H CH3 H
Base
OH H H3C
H CH3 H
Note the deprotonation step at the end. Industrially ethanol is prepared from ethylene with H2O and phosphoric acid at 250˚C. In the laboratory the procedure is modified into what is called oxymercuration. CH3
1.Hg(OAc)2 , H2 O/THF
CH3
2. NaBH4
OH
The process is a two-reaction sequence. The numbers indicate that each of the steps is carried out separately. This is different than showning steps in a mechanism for a single particular reaction. If two separate reactions are carried out, this must be clearly indicated.
The first part of the reaction is analogous to halohydrin formation with the electrophilic addition of mercuric ion to the alkene to form a mercurinium ion and then water comes in. The separate second step in the sequence is a reduction reaction to break the organomercury bond to give the alkane.
Hg+
OAc Hg
CH3
OAc
HgOAc CH3
OAc CH3
CH3
O H
OH2
H -
OAc
HgOAc CH3
2.NaBH4
OH
OH
This reaction follows Markovnikvo's rule - formation of most stable carbocation.
4. Hydration of Alkenes - Hydroboration Borane, BH3, adds to double bonds C
C
+ H
H B
H
BH2
H
This is a tri hydride and all three hydrides add to form a trialkyl borane CH2CH3 CH2=CH 2 + BH 3
CH3CH2
B CH2CH3
The reaction is useful because the trialkyl borane when treated with aqueous hydrogen peroxide in basic solution yields alcohols. The overall reaction adds the elements of H-OH in an anti-Markovnikov fashion (regio chemistry) and in a syn (or same side) stereochemistry CH2CH3 CH2=CH 2 + BH 3
CH3CH2
B CH2CH3 H2O2, H2O OH
3 CH3CH2OH
The following reaction shows the anti-Markovnikov regio chemistry of the reaction H
H3C
H BH3
H2O 2,HO
OH
--
H3C
H2O
H
NOTE: The reaction arrow may be written: 1. BH3 2.
H2 O2 , HO--, H2 O
It is a TWO REACTION sequence.
Unlike other additions, the addition of borane to alkenes is a single step reaction. The dotted lines indicate bonds being made and broken simultaneously. H H H3C
B +
H
H H3C
d- H B H
d+
SYN addition
Both steric and electronic arguments predict the regiochemistry, but steric influences are probably most important.
During the oxidation step (B-C bond replaced by C-OH) the boron is replaced by OH with the same stereochemistry so the overall addition is syn, nonMarkovnoikov.
5. Carbenes: Formation of Cyclopropanes Divalent carbon compounds are usually too unstable to isolate & often too reactive to be of much synthetic use (react too indiscriminately). Two exceptions are illustrated below. Cl
Cl C
+
:CCl2
KOH/H2O
CHCl3
Dichlorocarbene can be prepared readily from chloroform and KOH. This divalent carbon species reacts with double bonds stereospecifically to give the corresponding cyclopropanes.
H H3C
Cl
KOH / CHCl3
H CH2CH3
H2O - EtOH
Cl C
H
H
H3C
CH2CH3
Stereospecific: syn-addition
Dichlorocarbene can be viewed as a “neutral carbocation,” that is sp2 hybridized:
Empty p-orbital Cl
:CCl2
Filled sp2 orbital
Cl
Dichlorocarbene
A useful way to make cyclopropanes themselves is by the Simmons-Smith reaction where activated zinc (so-called zinc-copper couple) pulls the two I’s from diiodomethane to give a reactive intermediate that behaves as if it were :CH2 & that reacts nicely with alkenes to give cyclopropanes. CH3 H3C
CH3 CH2I2 - Zn(Cu) Et2O
H3C
H H
Simmons-Smith Rxn: CH2I2 + Zn(Cu)
Note that sterics plays a role in directing the incoming reactant to the less hindered face of the double bond.
5. Hydrogenation of Alkenes - Reduction Addition of H-H
+
H
H
Catalyst
H
H
Platinum and palladium are the usually employed catalysts - Pt in the form of PtO2 and Pd on charcoal written Pd/C. Ususally occurs with syn hydrogenation - both hydrogens add to the same side of the double bond. CH3
CH3 H2, PtO2 acetic acid
CH3
H H
H H CH3
C C
Very sensitive to steric hindrance in some molecules.
H H
C C
Alkenes are more reactive to hydrogenation than other groups with double bonds such as the carbonyl groups. So reaction is selective. O
O H2, Pd/c ethanol
6. Hydroxylation Hydroxylation of an alkene is the addition of an -OH group to each of the carbons in the double bond. It is essentially an oxidation reaction. The intermediate in the reaction is a cyclic osmate that is cleaved in a second step with aqueous sodium bisulfite
hydroxylation
Overall reaction
C
C C OH OH H
H H
C
H O
OsO4
NaHSO3 H2O
O Os
Pyridine (Py)
O
O
H
H
8. Oxidative Cleavage a. Ozonolysis C
C
O3
Zn HOAc/H2 O
C
O
+
O
C
Aldehydes and ketones
In the presence of Zn in the second step, the products are limited to aldehydes and ketones. This reaction can be used as an analytical too. Show examples
OH OH
b. KMnO4 is neutral or acidic media cleaves the C=C R
C H
CH2
O
KMnO4
R
H3O+
C OH
O R C H R R C H2C
Show examples
R
C
acids OH
R R
C O
Ketone
CO2 carbon dioxide
