Exam III
Alcohol Synthesis
Alcohol Reactions
Acetal Reaction
Fisher Ester forwards and backwards
Oxidation of Alcohols
Reduction of Aldehydes, Ketones, Acids
Grignard Reactions
Alcohol and Epoxide Syntheses
H
H
+
O
Oxymercuration/
Deoxymercuration
C
C
C
HgOA c+
C
C
C
H2O
C
OH
C
C
Hg
OAc+
Alkoxymercuration/
C
Dealkoxymercuration
C
C
C
C
C
C
CH 3OH
C
H
+
OCH3
C
NaBH4
C
C
+
H
C
C
C
C
C
H2O
C
C
C
C
O+
O
C
H
O
H+
C
HgOAc
H
C
H
O
Hg
OAc+
Epoxide Ring
Opening - Acid
C
HgOAc
H3C
HgOA c+
NaBH4
OH
C
C
OH
C
OH
H
Epoxide Ring
Opening - Base
C
C
C
OH
OH
OH-
H2O
C
C
C
C
O
C
C
+ OH-
OH
OH
+
H
C
C
OH
O
Hydration Addition of Water
C
C
C
H+
C
C
+
C
H2O
C
H3C
Alcohol Addition
C
C
C
C
C
+
C
CH 3OH
C
+
H
C
C
H
OH
Halohydrin Reaction
C
C
C
C
C
C
Br
+
OH-
C
C
C
Br
C
+ H+
H
OCH3
O
H
Br+
C
H
H
H+
C
C
C
C
H
+ H+
Alcohol Oxidations
C
C
OH
PCC
CH2Cl2
C
PCC
CH2Cl2
C
C
C
C
C
KMnO 4, H+, H2O
C
C
C
C
O
OH
C
C
O
OH
C
O
O
OH
C
C
C
C
K2Cr2O7,
H2SO4, Heat
C
C
C
O
C
C
OH
KMnO 4, H+, H2O
C
C
OH
O
C
C
OH
K2Cr2O7,
H2SO4, Heat
C
C
OH
Reductions that make alcohols
O
C
C
OH
C
HCN
C
C
C Cyanohydrin
CN
OCH3
OH
CH 3OH
H+, H2O
C
C
C
OCH3
Hemiacetal
OH
1. C2H5MgBr
2. H2O, H+
C
C
C
C2H5
OH
LiAlH4, H2O
C
C
C
OH
NaBH4, H2O
C
C
C
CH 2OH
H+, H2O
C
C
C
OCH3
Acetal
Fisher Ester Forwards
+
O
O
OH
OH
H
+
C
C
H
OH
C
C
C
OH
C
OH
C-C-OH
C
C
OH
H
O
C
+
+
C
H
C
H2O +
+O
+
C
O
H
O
C
C
C
OH
H
C
OH
O
C
H+ +
C
C
C
OH
O
C
C
O
C
C
O C
C
+ H+
Fisher Ester Backwards
+
O
H+
C
C
O
C
C
C
O
H
C
O
OH
C
C
C
C
O
C
C
C
O
C
C
+O
H
+
H2O
C
C
OH
OH
OH H
O
C
+
C
H+
C
C
O
C
OH
OH
C
+ H+
C
H
+
O
C
O
H
HO
C
OH
C
C
C
+ H+
C
OH
Acetal Formation
O
H
O
H
O
H+
H3C
C
CH3
H3C
C
CH3
H3C
C
CH3
CH3OH
H
H
O
H3C
H
O
C
CH3
O
CH3
H+ + H3C
H
O
C
CH3
O
CH3
H3C
C
CH3
O
CH3
H
H
H3C
C
CH3
O
CH3
CH3OH
+ H2O
O
CH3
C
CH3
O
CH3
H3C
H3C
O
CH3
C
CH3 + H+
O
CH3
Acetal Cleavage
If using 1,2 propadiol as your alcohol
...but it has to be
pushed off by H2O
H
Now, the water
gives up an H+
to get rid of
H its charge.
H
C
C
O
O
C
C
C
C
O
O
C
H+
C
C
O
O
C
C
C
H
H2O
C
O
H+ +
C
O
O
C
C
O
C
H
H
H
C
C
O
O
C
C
H
H
C
C
C
O
O
C
C
O
H3C
C
C
O
CH3
H+
C
C
O
H3C
O
C
H
H2O
CH3
C
C
H
H+ +
H
O
C
C
C
C
H
C
O
CH3
O
CH3
H O
C
C
C
CH3
CH3
O
H+ +
O
O
H
...but it has to be
pushed off too.
If using two methanols as your alcohol
H
H
O
C
C
C
O
H
O
C
C
H+ +
Now we make
the other oxygen C
a good leaving
group...
C
Now we just get
rid of the last
H
H+
O
H
O
C
This makes the
oygen a good
leaving group...
C
C
C
H
C
C
O
CH3
SOCl2 Mechanism
Cl
Cl
S O
C
C
OH
+
Cl
C
C
H+ + O
O
S
H
Cl
S
O
O
-
C
H
O
Cl-
+
C
S
O
S
H
Cl
C
O
+ Cl-
O
C
Cl
Cl
HCl
PCl3 Mechanism
Cl
C
C
PCl3
OH
C
C
O
P
H
Cl
C
Cl
C
C
C
O
P
H
Cl
Cl + HO
Cl + Cl-
P
Cl
Cl
POCl3 Mechanism
O
Cl
P
Cl
C
C
OH
O
O
Cl
C
C
O
P
H
Cl
C
Cl
Cl
C
O
P
H
Cl
Cl + Cl-
O
C
C
Cl + HO
P
Cl
Cl
Grignard are not mysterious. They are made using the following reaction,
C-C-C-Br + Mg(s) ---> C-C-C-Mg-Br (a Grignard)
If we account for all of the charges in the Grignard, Mg has a 2+ charge (Mg2+) and since
the charges must balance, the Br is negative (Br-) and the carbons must be negative also
(CH3CH2CH2-). This makes the carbon portion of the compound a very powerful
nucleophile that tends to attack C=O's to make alcohols. See the following reaction;
C
C
C
Br
Mg(s)
C
C
C
O
C C
H
MgBr
OMgBr
C
C
C
C
C
H+, H2O
OH
C
C
C
C
C
+ Mg(OH)Br
The point is that Grignards generally make alcohols although other compounds can be
made. See the following reactions;
C
C
C
O
H C
H
MgBr
C
O
C C
H
C
C
C
OH
OH
C
C
C
C
C
O
C
C
OH
C
C
C
C
C
C
C
O
CO, HCl
C
C
C
C
H
O
C
C
O
Cl
C
C
C
C
C
O
O
C C OCH3
C
C
C
C
C
Reducing Agents and Their Products
Reducing
Agent
C=C
C=O Ket
C=O Ald
COOH
COOR
COCl
CN
CONH2
Benzene
LiAlH4, H2O
No Rxn
C-OH
C-OH
C-OH
C-OH
C-OH
C-NH2
C-NH2
No Rxn
NaBH4
No Rxn
C-OH
C-OH
No Rxn
No Rxn
No Rxn
DIBAH, 78C
No Rxn
Raney Ni / H2
No Rxn
C=O
No Rxn
C-C
C-OH
C-OH
C-OH
C-OH
C-OH
Zn(Hg) HCl
No Rxn
Alkane
Alkane
No Rxn
No Rxn
Alkane
No Rxn
N2H4, KOH,
Heat
No Rxn
Alkane
Alkane
No Rxn
No Rxn
Alkane
No Rxn
No Rxn
No Rxn
No Rxn
No Rxn
No Rxn
C=O
No Rxn
C-C
C-OH
C-OH
C-OH
C-OH
Alkane
B2H6,
Diglyme
No Rxn
No Rxn
No Rxn
C-OH
H2/Pd/BaSO4/
Quinoline
No Rxn
C-OH
C-OH
Li(tButO)3Al
H
H2, 1000psi,
Pt, Pd, Ni,
Ru, or Rh
C-NH2
C-NH2
No Rxn
Cyclohe
xane
No Rxn
C=O
1) Please supply the product for each of the following reactions.
C
C
1. PBA
2. H2SO4, H2O
H2SO4, H2O
K2Cr2O7
C
1. BH3
2. KOH, H2O2, H2O
Hg(OAc)2
CH 3OH, NaB H4
HO
1. PCC
2. C-C-MgBr
CH3
P/I2
OH
OH
KMnO 4, H2SO4, H2O
H2O, Br2
C
I
C
C
1. POCl3
2. Mg, Ether
OH
3. Water
C
1. Mg
2. Acetone
3. H2O
C
H3C
C
CH3
C
1. PBA
2. C2H5MgCl
3. H2O
H3C
1. Tosyl Chloride
CH3
COOH
O
C
C
2. NaCN
OH
1. SOCl2
1. SOCl2
2. CH3OH
C
2. n-butanol
OH
O
C
C
O
C
LiAlH4
C
C
C
C
C
OH
HI
C
C
C
OsO4, H2O2
BH3, H2O2
H2O, KOH
C
CH3
1. PBA
2.C-C-MgCl
3. H2O
OsO4, H2O2, H2O
CH3
C
C
C
1. HBr
2. Mg, dry Ether
3. Acetone
4. Water
C
C
C
1. H2SO4, H2O
2. PCC
C
C
C
Raney Ni, H2
O
H
C
C
C
Cl
O
KOH, Ether
C
OH
C
C
C
1. PCC
2. C-C-MgCl
3. H20, H+
C
C
CMgCl
CO, HCl
C
Cl
C
C
C
C
C
C
OH
C
C
C
C
SOCl 2
C
C
OH
C
C
C
C
C
1. Ag2O
2. C-C-OH
C
1. BH3
2. H2O2, NaOH, H2O
Cl 2, H2O
1. Hg(OAc)2
2. C-C-OH
3. NaBH4
O
H2SO4
I
C
LiAlH4
C
C
HO-C-C- OH, H2SO4
2) Suppose you wanted to carry out the following reaction using HBr as your reagent.
Why would this be a poor choice of reagent to carry out this reaction?
OH
Br
C H3
C H3
HBr ?
3) Two students are assigned the synthesis of t-butyl ethy ether. One uses process
number one below, and the other uses process number two. Only one student obtains the
desired product. Which one was it and why?
#1
C
C
OH
Na
C
C
O-
C
C C Br
C
C
C
#2
C
C
C
C
O
C
C
C
C
OH
Na
C
C
O-
C C Br
C
C
4) There are a number of ways of substituting a halogen for an alcohol group, but some
ways are better than others. What advantage is there in using PCl3 rather than HCl in the
chloride substitution reactions? Give an example.
5) Esters do not have to be made from alcohols and acids. It is possible to make an ester
using a ketone and acid instead. Please give the mechanism for the formation of the
following ester in a base;
O
O
O
C
NaO H Ca ta ly st
C C C + C C
C C O C C
+ H2O
OH
6) Please draw all of the steps for the acid catalyzed cleavage of propyl acetate.
7) What is the mechanism for the reaction between ethanol and thionyl chloride
(SOCl2)?
8) 3-bromo-1,2-epoxybutane reacts with sodium methoxide to give a new oxirane, 1methoxy-2,3-epoxybutane. Suggest a mechanism for this reaction.
Br
H3C
C
C
C
CH 3ONa
CH 3OH
H3C
O
C
C
C
OCH 3 + Br-
O
9) Please give the mechanism for the formation of the hemiacetal made when ethanol
and acetone are combined in the presence of H2SO4
10) Please show the mechanism for the reaction between methyl cyclohexene, bromine,
and water. Four products are formed during this reaction. Give the complete mechanism
for just one product but show how each product is formed and label them R,S
appropriately
11) Esters do not have to be made from alcohols and acids. It is possible to make an
ester using a ketone and acid instead. Please give the mechanism for the formation of the
following ester in a base;
O
O
C C C +
NaO H Ca ta ly st
C C
O
C
C C O C C
+
OH
H2O
12) The peptide bond that links amino acids in proteins is a type of ester bond. This
bond is easily broken in acidic environments but not in basic environments. Please show
how the breakdown of this bond in an acidic environment and discuss why it would not
easily be broken down under basic conditions.
R H
R
HO C C N C C NH 2
O H
O H
R H
H+ , H2O
2
HO C C N H
O H
13) A grad student wanted to make diphenyl methanol using a Grignard reaction
between phenyl magnesium bromide and benzaldehyde. To make sure his yield was
good he added twice as much benzaldehyde as Grignard reagent and got a lot of white
crystalline product. When he analyzed his product he found that he had not made
diphenyl methanol, but diphenyl methanal (also called benzophenone) instead. When he
asked his research director about it he was told that he should have used equivalent
amounts of benzaldehyde and Grignard instead. Doing so, he obtained his desired
product. Please explain, using reactions, what had gone wrong with the original synthesis
and why the product changed when the amount of benzaldehyde changed. Show the
mechanism of each reaction. Hint: One step of this reaction produces a very unusual
leaving group.
14) Please draw the complete mechanism for the based catalyzed cleavage of an ester.
The overall reaction should be,
O
O
C
C
O
C
OH-, H2O
C
C
C
OH
+ HO
C
C
15) Please give an example of a reaction where an alcohol is acting like an acid, and
another where it is acting like a base.
16) Using any alkane that is four carbons or less, synthesize methyl cyclohexane.
17) Starting with alcohols of two carbons or less synthesize 4 bromobutanol.
18) Please label as R and S all the products formed by the halohydrin addition of Br2 and
water to cis 2 pentene. There are four products in all.
19) Using any alkane that is four carbons or less synthesize the following;
OH
O
C
C
C
C
O
C
C
C
C
C
O
C
C
OH
20) Using compounds of two carbons or less, synthesize the following compounds.
O
C
C
C
O
O
C
C
C
C
O
C
O
OH OH OH
C
C
C
21) The SN2 reaction between ethanol and methoxide is doomed to failure even though
methoxide is a stronger nucleophile than hydroxide. Why does this reaction fail?
C2H5OH + CH3O-  C2H5OCH3 + OH- (does not occur)
21b) Since the above reaction does not occur we tend to use compounds like TosCl to
help the reaction along. What exactly does the TosCl do to help the reaction occur? (Two
things).
22) Please supply the R,S configurartion for each of the following compounds.
CO O H
Cl
H
H C Cl
H C
Cl C
Cl C H
CH 3
H
_________
A
CO O H
H
HOOC
C Cl
Cl C
CH 3
C H
H C Cl
CH 3
Cl
_________
B
________
C
CO O H
CH 3
________
D
22b) Draw the R,S configuration of the enatiomers/diastereomers missing from the
above set of compounds.
23) Please label the following compounds as R and S. Also, draw and label the missing
diastereomer/enantiomer.
CH3
Cl
Cl
C
H
Cl
C
CH3
H
_________
A
Cl
H3C
C
H
H
C
CH3
H
C
Cl
H
C
CH3
CH3
Cl
_________
B
________
C
Please indicate the enantiomer/diastereomer pairs below.
Diastereomers =
Enantiomers =
Meso Pairs =
________
D
1) Please supply the product for each of the following reactions.
OH
C
H SO , H 2O
2 4
C C
O
CO2 + C
1. PBA
2. H2SO4, H2O
C
K 2Cr2 O7
OH
OH
CH3
Hg (O Ac ) 2
1. BH3
HO
2. KOH, H2O2, H2O
C H 3 O H , Na BH 4
CH 3
OH
OCH3
OH
1. PCC
2. C-C-MgBr
P/I2
I
OH
O
KMnO 4, H2SO4, H2O
CH3 Br
C
H2 O
C C
C C
C
C
C
Br2
C
C
H
OH CH3
C
OH
I
C
OH
C C
1) M g
C
C
C
2) Ac et o ne
C
C
C
C
H3C
C
H3C
O
C C C
OH
CH3
C
H3C
CN
COOH
C
O
C
C
C
1. SOCl2
2. n-butanol
CH3
O
SOCl2
CH3 O H
C
O
OH
3) H 2 0
C
H3C
1. Tosyl Chloride
2. NaCN
OH
C
C2H5
2) C 2 H 5 MgCl
CH 3
1. POCl3
2. Mg, ether
3. H2O
CH3
C
3) H 2 O
1) PB A
OH
C
C
C
O
O
CH3
C
C
O
C
LiAlH4
C
C
OH and
H3C
OH
C
OH OH
C
C
C
C
C
OH
HI
BH3, H2O2
H2O, KOH
C
C
C
C
I
HO
C
C
C
C
1. PBA
2.C-C-MgCl
3. H2O
C
CH3
C
Cl
C
C
1. PCC
2. C-C-MgCl
3. H20, H+
C
C
1. HBr
2. Mg, dry Ether
3. Acetone
4. Water
C
C
C
1. H2SO4, H2O
2. PCC
C
C
C
Raney Ni, H2
C
C
C
C
C
C
C
C
C
C
C
HO
C
C
Cl
LiAlH4
C
C
CMgCl
CO, HCl
C
C
C
C
C
C
C
C
C
C
1. BH3
2. H2O2, NaOH, H2O
C
OH
C
C
C
C
C
C
OH
H2SO4
C
C
C
C
C
C
C
O
C
C
I
C
C
C
C
1. Ag2O
2. C-C-OH
C
O
C
C
C
C
C
C
1. Hg(OAc)2
2. C-C-OH
3. NaBH4
C
O
C
C
C
C
Cl 2, H2O
Cl
C
C
C
OH Cl
C
H
SOCl 2
C
OH
O
C
C
OH
C
C
C
O
OH
C
OH
C
H
OH
C
C
O
OH
C
C
CH3
OsO4, H2O2, H2O
KOH, Ether
C
O
C-C
CH3
C
OH
OH
CH3
C
OsO4, H2O2
C
C
HO-C-C- OH, H 2SO4
C
C
O
C
C
C
O
C
C
O
C
C
OH
2) Suppose you wanted to carry out the following reaction using HBr as your reagent.
Why would this be a poor choice of reagent to carry out this reaction?
OH
Br
C H3
C H3
HBr ?
HBr should not be used because it would also attack the double bond. A better reagent
would be PBr3 because it does not attack double bonds.
3) Two students are assigned the synthesis of t-butyl ethy ether. One uses process
number one below, and the other uses process number two. Only one student obtains the
desired product. Which one was it and why?
#1
C
C
OH
Na
C
C
C
C C Br
C
O-
C
C
#2
C
C
C
O
C
C
C
C
OH
Na
C
C
C
C C Br
O-
C
C
Although the general rule is to use the larger nuc- and the smaller substrate,
doing so in this case would only lead to E2 elimination on #2. By using the
smaller nuc- and larger substrate in #1 the reaction would go SN1 which would
mean that you would get a lot of by-products but you would end up getting more
product also (SN1 major, E1 minor).
4) There are a number of ways of substituting a halogen for an alcohol group, but some
ways are better than others. What advantage is there in using PCl3 rather than HCl in the
chloride substitution reactions? Give an example.
HCl can react with double bonds and PCl3 cannot, so in some cases only PCl3 can be
used. See below;
Cl
HCl
OH
Cl
PCl3
Cl
5) Esters do not have to be made from alcohols and acids. It is possible to make an ester
using a ketone and acid instead. Please give the mechanism for the formation of the
following ester in a base;
O
O
C C C +
O
NaO H Ca ta ly st
C C
C
C C O C C
H2O
+
OH
O
O
C
OH
C
O
-
C
C
C
-
O
C
C
C
C
O
O
C
C
-
OH
O
C
+ H2O
H2O
O
H2O + OH + C
O
C
O
C
C
C
C
OH H
O
C
C
C
C
H
-
+ OH
H
6) Please draw all of the steps for the acid catalyzed cleavage of propyl acetate.
+
O
H+
C
C
O
C
C
C
O
H
C
O
OH
C
C
C
C
O
C
C
C
O
C
C
+O
H
+
H2O
C
C
OH
OH
OH H
O
C
+
C
H+
C
C
O
C
OH
OH
C
C
+ H+
H
+
O
C
O
H
HO
C
C
C
C
+ H+
C
OH
OH
7) What is the mechanism for the reaction between ethanol and thionyl chloride
(SOCl2)?
Cl
Cl
S O
C
C
OH
Cl
+
C
C
SO2 + HCl +
O
S
H
Cl
C
C
O
-
Cl
C
Cl-
C
C
C
+
O
S
H
Cl
O
S
Cl
O
+ Cl-
O
+ H+
8) 3-bromo-1,2-epoxybutane reacts with sodium methoxide to give a new oxirane, 1methoxy-2,3-epoxybutane. Suggest a mechanism for this reaction.
Br
H3C
C
C
C
CH3ONa
CH3OH
H3C
C
O
C
OCH3 + Br-
C
O
Br
H3C
C
Br
C
C
CH3O-
H3C
O
C
C
C
OCH3
H3C
C
C
C
OCH3 + Br-
O
O
9) Please give the mechanism for the formation of the hemiacetal made when ethanol
and acetone are combined in the presence of H2SO4
O
C
C
C
H+
C
O
H
C
C
C
O
H
C
C
HO C C
O
H
C
C
C
H
O
C
C
O
H
C
C
O
C
H+ +
C
C
10) Please show the mechanism for the reaction between methyl cyclohexene, bromine,
and water. Four products are formed during this reaction. Give the complete mechanism
for just one product but show how each product is formed and label them R,S
appropriately
12) The peptide bond that links amino acids in proteins is a type of ester bond. This
bond is easily broken in acidic environments but not in basic environments. Please show
how the breakdown of this bond in an acidic environment and discuss why it would not
easily be broken down under basic conditions.
R H
R
HO C C N C C NH 2
O H
O H
R
HO
C
C
O
H
N
C
C
O
H
H
HO
HO
C
C
O
H
H
N
O
NH2
C
C
O
H
H
H
O
H
R
C
C
N
C
C
O
H
O
H
H
+ H+
H+ +
H+
HO
NH2
H2O
HO
NH2
HO
R
H
C
C
N
O
H
C
H
R
H
C
C
N
O
H
NH2
HO
C
C
O
H
R
C
C
O
H
H
C
C
O
H
H
H
O
H
R
C
C
N
C
C
O
H
H
O
H
H
H
NH2
R
R
R
R
C
HO
O H
H
R
R
O
HO C C N H
2
R
H
R
R H
H+ , H2O
C
HO
NH2
R
O
NH2
NH2
C
H
NH2
13) A grad student wanted to make diphenyl methanol using a Grignard reaction
between phenyl magnesium bromide and benzaldehyde. To make sure his yield was
good he added twice as much benzaldehyde as Grignard reagent and got a lot of white
crystalline product. When he analyzed his product he found that he had not made
diphenyl methanol, but diphenyl methanal (also called benzophenone) instead. When he
asked his research director about it he was told that he should have used equivalent
amounts of benzaldehyde and Grignard instead. Doing so, he obtained his desired
product. Please explain, using reactions, what had gone wrong with the original synthesis
and why the product changed when the amount of benzaldehyde changed. Show the
mechanism of each reaction. Hint: One step of this reaction produces a very unusual
leaving group.
MgBr
Note: For clarity, I will represent the Grignard
as just the phenyl nucleophile.
H
C
O
Benzophenone
O
O
C
C
H
Benzaldehyde
+ H- unusual
Grignard
leaving group
H
H
H
C
H
OH
C
H
O
O
C
H2O
OH- +
Without the extra benzaldehyde present, the H- would have nothing to attack
except the benzophenone converting it to diphenyl methanol, the desired product.
14) Please draw the complete mechanism for the based catalyzed cleavage of an ester.
The overall reaction should be,
O
C
C
O
C
C
O
C
C
O
OH-, H2O
C
C
OH
+ HO
C
O
O
C
C
OH-
C
C
OH
C
O
O
C
C
C
C
OH
+
O
C
C
H2O
HO
C
C
+ OH-
15) Please give an example of a reaction where an alcohol is acting like an acid, and
another where it is acting like a base.
Water behaves like an acid any time it gives off an H+ like when a nucleophile
takes a hydrogen off of water.
Water behaves like a base when the oxygen in water attacks something like
carbon with a + charge.
16) Using any alkane that is four carbons or less, synthesize methyl cyclohexane.
C
C
C
C
1. Br2, h
2. EtO-, EtOH
3. Br2, dark
4. tButO-, tButOH
C
C
C
C
CH3
CH3
H2/Pt
, Pressure
C
C
1. Br2, h
2. EtO-, EtOH
3. Br2, dark
4. 2x NaNH2
C
C
C
C
17) Starting with alcohols of two carbons or less synthesize 4 bromobutanol.
C
H3C
C
OH
OH
PCC
C
1. SOCl2
2. Mg(s), dry ether
C
OH
O
H3C
H+, H2O
C
C
Br
C
MgCl
1. SOCl2
2. tButO-, tButOH
3. NBS
C
C
C
KCN,
THF
Br
C
C
C
OH
1. H+, H2O, 
2. LiAlH4
Br
C
C
C
CN
HBr, PBA
C
C
C
CN
18) Please label as R and S all the products formed by the halohydrin addition of Br2 and
water to cis 2 pentene. There are four products in all.
19) Using any alkane that is four carbons or less synthesize the following;
C
C
C
C
O
1. Br2, h
2. tButO-, tButOH
C
3. KMnO4, H+, H2O, 
C
C
O
OH
H2SO4
Heat
C
C
C
C
O
C
C
OH
C
C
C
C
C
C
C
C
C
1. Br2, h
2. KOH, Ether
C
C
1. Br2, h
O
2. EtO-, EtOH
C
3. Br2, dark
H
4. tButO-, tButOH
5. BH3, H2O2, NaOH, H2O
6. PCC
1. Br2, h
2. EtO-, EtOH
BrMg
3. Br2, dark
4. Mg(s), dry ether
C
C
C
C
1. Br2, h
2. tButO-, tButOH
3. BH3, H2O2, NaOH, H2O
O
C
OH
C
H
H+, H2O
C
C
C
C
C
MgBr
C
OH
OH
H2SO4
H3C
C
1. Br2, h
2. tButO-, tButOH
H2C
CH2
C
C
C
O
C
C
20) Using compounds of two carbons or less, synthesize the following compounds.
O
C
C
O
C
O
C
C
C
C
O
OH OH OH
C
O
C
1. Br2, h
2. KCN, THF
3. H+, H2O, 
C
1. Br2, h
2. KOH, Ether
CH4
C
C
C
C
C
C
H3C
H2SO4
Heat
C
C
C
CH3
OH
C
C
C
Br
C
C
C
O
CH3
CH3O-
1. Br2, h
2. tButO-, tButOH
3. OsO4, H2O2
C
O
C
O
OH
1. Br2, h
2. EtO-, EtOH
3. O3, (CH3)2S
C
C
C
1. Br2, h
2. KOH
3. Na(s)
C
C
O
1. Br2, h
2. Mg(s)
3. CO, HCl
4. LiAlH4
5. PBr3
CH4
C
1. Br2, h
2. Mg(s), dry ether
3. CO, HCl
3. LiAlH4
4. PBr3
H
C
O
H
HO
C
H+
C
C
C
C
O
O
OH
Br
1. EtO-, EtOH
2. NBS
3. Br2, dark
4. KOH, ether (3x)
OH OH OH
C
C
C
21) The SN2 reaction between ethanol and methoxide is doomed to failure even though
methoxide is a stronger nucleophile than hydroxide. Why does this reaction fail?
C2H5OH + CH3O-  C2H5OCH3 + OH- (does not occur)
It fails because alcohols are really acids, so they donate their hydrogen to the
MeO- in an acid/base neutralization.
21b) Since the above reaction does not occur we tend to use compounds like TosCl to
help the reaction along. What exactly does the TosCl do to help the reaction occur? (Two
things).
TosCl is just a fancy SOCl2, so it does two things,
a) it turns the OH into a good leaving group (main thing)
b) it is large so it does not do any SN2 reactions.
22) Please supply the R,S configurartion for each of the following compounds.
CO O H
Cl
H
H C Cl
H C
Cl C
Cl C H
CH 3
H
CO O H
HOOC
C Cl
Cl C
CH 3
C H
H C Cl
CH 3
__S, R___
A
H
Cl
__R, S___
B
CO O H
CH 3
___R, R__
C
__S, R__
D
22b) Draw the R,S configuration of the enatiomers/diastereomers missing from the
above set of compounds.
H
Cl
C
COOH
H3C
C
Cl
The S, S version is missing =>
H
23) Please label the following compounds as R and S. Also, draw and label the missing
diastereomer/enantiomer.
CH3
Cl
Cl
C
H
Cl
C
CH3
H
A
__R, R___
Cl
CH3
H3C
C
H
H
C
CH3
H
C
Cl
H
C
Cl
H
C
CH3
H3C
C
Cl
CH3
Cl
B
C
__S, R__
__R, S__
Please indicate the enantiomer/diastereomer pairs below.
Diastereomers = AB, AC, BD, CD
Enantiomers = AD, BC
Meso Pairs = B & C are meso to each other
H
D
__S, S__
Chem 240
Exam #3
Name___________________
December 12, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full
credit.
Question
1(10 )
Credit
2(10)
3(44)
4(16)
5(20)
TOTAL
1) Please discuss, and give examples, of the relative acidity of 1, 2, and 3 alcohols.
Why is one more acidic than another?
2) Please give the mechanism of an acid halide with an alcohol to form an ester. Use the
following reactants;
O
C
C
C
Cl
C
OH
3a) It is well known that Grignards cannot be made when there is water or any other
compound that can provide an H+ present. Why is this so?
3b) Grignard cannot be made in the presence of aldehydes or ketones either. Somehow
these compounds provide H+ to the solution. How does this happen?
4) Please give the complete mechanism for the cleavage of the ester, ethyl acetate, with
H+ and water. Note: Some people try to draw the forward reaction (making of the ester)
and then draw all the arrows backwards. Please refrain from doing so. Besides, it
doesn’t work.
5) Please supply the product for each of the following reactions. If there is no product,
write “No Rxn.”
PBA
1. O3, (CH3)2S
2. LiAlH4
1. KMnO4, H+, H2O, heat
2. CH3OH, H2SO4
1. Hg(OAc)2
2. C2H5OH
3. NaBH4
CH3
cold dil. KMnO4, OH-
H2SO4, CH3OH
Br2, H2O
BH3, H2O2,
NaOH, H 2O
6) Starting with any compound that is three carbons or less, synthesize the following
compounds.
CH3
O
Cl
C
O
C
C
You MUST use Grignard
(do not use ozonolysis)
C
C
C
O
C
C
Use two different methods
OH
H2C
OH
C
CH2
C
C
C
O
C
C
C
C
O
C
C
C
C
O
C
Do not use Grignard or ozonolysis
OH OH OH
H2C CH CH2
Chem 240
Exam #3
Name___Answer Key______
December 12, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full
credit.
Question
1(10 )
Credit
2(10)
3(44)
4(16)
5(20)
TOTAL
1) Please discuss, and give examples, of the relative acidity of 1, 2, and 3 alcohols.
Why is one more acidic than another?
The more acidic alcohol is the smaller alcohol (ie: 1). They have the fewest
methyl groups pushing into the OH group. This causes the oxygen to pull as
many electrons from the surrounding atoms as possible making the hydrogen
more acidic (it leaves easier). As methyl groups are added the entire OH group
become a good leaving group and the compound actually becomes more basic.
Therefore 1> 2> 3 in terms of acidity.
2) Please give the mechanism of an acid halide with an alcohol to form an ester. Use the
following reactants;
O-
O
C
C
C
Cl
C
OH
C
O
C
Cl
+O
C
H
C
C
O
-
+ Cl
C
+O
H
C
C
C
+ H+
C
O
C
C
3a) It is well known that Grignards cannot be made when there is water or any other
compound that can provide an H+ present. Why is this so?
Grignards are powerful nucleophiles (bases) and are easily neutralized in the
presence of H+, therefore no H+ can be present when making a Grignard.
3b) Grignard cannot be made in the presence of aldehydes or ketones either. Somehow
these compounds provide H+ to the solution. How does this happen?
This happens because of keto-enol tautomerism. The enol form of the tautomer is
an alcohol which provides the H+ ions that destroy the Grignard. See below;
OH
O
C
C
C
C
C
CH2
4) Please give the complete mechanism for the cleavage of the ester, ethyl acetate, with
H+ and water. Note: Some people try to draw the forward reaction (making of the ester)
and then draw all the arrows backwards. Please refrain from doing so. Besides, it
doesn’t work.
+
O
H+
C
C
O
C
C
C
O
H
C
O
OH
C
C
C
C
O
C
C
C
O
C
C
+O
H
+
H2O
C
C
OH
OH
OH H
O
C
+
C
H+
C
C
O
C
OH
OH
C
+ H+
C
H
+
O
C
O
H
HO
C
OH
C
C
C
+ H+
C
OH
5) Please supply the product for each of the following reactions. If there is no product,
write “No Rxn.”
O
PBA
CH 3
1. O3, (CH3)2S
2. LiAlH4
HO HO
CH 3
O
C
O
H3C
O
CH 3
1. KMnO4, H+, H2O, heat
2. CH3OH, H2SO4
CH 3
1. Hg(OAc)2
2. C2H5OH
3. NaBH4
CH3
CH 3
OC2H5
cold dil. KMnO4, OH-
OH
CH 3
OH
H2SO4, CH 3OH
OCH 3
CH 3
Br
Br2, H2O
OH
CH 3
BH3, H2O2,
NaOH, H 2O
OH
6) Starting with any alcohol or alkyl halide that is two carbons or less, synthesize the
following compounds.
CH3
O
Cl
C
O
C
C
You MUST use Grignard
(do not use ozonolysis)
C
C
C
O
C
C
Use two different methods
OH
H2C
OH
C
CH2
C
C
C
O
C
C
C
C
O
C
C
C
C
O
C
Do not use Grignard or ozonolysis
OH OH OH
H2C CH CH2
Chem 240
Exam #3
Name___________________
December 9, 2002
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
You may use a calculator.
Question
1(16 )
Credit
2(10)
3(24)
4(20)
5(20)
6(10)
TOTAL
1) Please name each of the following compounds.
O
O
O
OH
O
O
O
O
OH
OH
O
2) Suppose you wanted to carry out the following reaction using HBr as your reagent.
Why would this be a poor choice of reagent to carry out this reaction?
OH
Br
C H3
C H3
HBr ?
3) Please supply the product for each of the following reactions.
C
C
C
C
C
OH
BH3, H2O2
H2O, KOH
C
CH3
C
C
1. PBA
2.C-C-MgCl
3. H2O
OsO4, H2O2, H2O
CH3
C
HI
Cl
OH
KOH, Ether
C
C
C
1. PCC
2. C-C-MgCl
3. H20, H+
C
C
CMgCl
CO, HCl
OH
C
C
C
C
SOCl 2
C
C
OH
H2SO4
I
C
C
C
1. Ag2O
2. C-C-OH
5a) What is the mechanism for the reaction between ethanol and thionyl chloride
(SOCl2)?
5b) There are a number of ways of substituting a halogen for an alcohol group, but some
ways are better than others. What advantage is there in using PCl3 rather than HCl in the
chloride substitution reactions? Give an example.
6) Two students are assigned the synthesis of t-butyl ethy ether. One uses process
number one below, and the other uses process number two. Only one student obtains the
desired product. Which one was it and why?
#1
C
C
OH
Na
C
C
O-
C
C C Br
C
C
C
#2
C
C
C
C
C
C
OH
Na
C
C
C
O-
C C Br
C
O
C
C
7) Using any compound of two carbons or less, synthesize methyl ethyl ketone (2
butanone).
Extra Credit - Esters are usually made by reacting an alcohol with an acid but they do not
have to be. It is possible to make an ester using a ketone and acid instead. Please give the
mechanism for the formation of the following ester in a base;
O
O
O
C
Na O H Ca t a l y s t
C C C + C C
C C O C C
+ H2O
OH
Chem 240
Exam #3
Name__Answer Key_____
December 9, 2002
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
You may use a calculator.
Question
1(16 )
Credit
2(10)
3(24)
4(20)
5(20)
6(10)
TOTAL
1) Please name each of the following compounds.
O
O
O
Tetrahydrofuran
1,3-dioxane
OH
O
O
O
O
OH
OH
O
15 crown 5
1,2,4-pentatriol
2) Suppose you wanted to carry out the following reaction using HBr as your reagent.
Why would this be a poor choice of reagent to carry out this reaction?
OH
Br
C H3
C H3
HBr ?
Because the HBr would also react with the double bond to give the addition product also.
3) Please supply the product for each of the following reactions.
C
C
C
C
C
HI
OH
C
BH3, H2O2
H2O, KOH
C
C
HO
C
C
I
C
C
CH3
1. PBA
2.C-C-MgCl
3. H2O
CH 3
C C
OH
H
CH3
OsO4, H2O2, H2O
CH3
OH
C
C
C
C
OH
C
C
OH
KOH, Ether
Cl
C
OH
OH
1. PCC
2. C-C-MgCl
3. H20, H+
C
C
C
C
C
C
C
O
C
C
CMgCl
CO, HCl
C
C
C
C
H
OH
C
C
C
C
Cl
SOCl 2
C
C
C
H2SO4
OH
C
C
I
C
C
1. Ag2O
2. C-C-OH
C
C
C
C
C
O
C
C
C
C
5a) What is the mechanism for the reaction between ethanol and thionyl chloride
(SOCl2)?
Cl
Cl
S O
C
C
OH
Cl
+
C
C
SO2 + HCl +
O
S
H
Cl
C
C
O
-
Cl
C
Cl-
C
C
C
+
O
S
H
Cl
O
S
Cl
O
+ Cl-
O
+ H+
5b) There are a number of ways of substituting a halogen for an alcohol group, but some
ways are better than others. What advantage is there in using PCl3 rather than HCl in the
chloride substitution reactions? Give an example.
PCl3 does not allow rearrangements to occur and it is OH specific. HCl allows for
rearrangements and can add to double bonds. For example:
Cl
PCl3
OH
CH3
HCl
Cl
CH3
Cl
and many others
CH3
6) Two students are assigned the synthesis of t-butyl ethy ether. One uses process
number one below, and the other uses process number two. Only one student obtains the
desired product. Which one was it and why?
#1
C
C
OH
Na
C
C
-
O
C
C C Br
C
C
C
#2
C
C
C
C
O
C
C
C
C
OH
Na
C
C
O-
C C Br
C
C
Although the general rule is to use the larger nuc- and the smaller substrate, doing so in
this case would only lead to E2 elimination on #2. By using the smaller nuc- and larger
substrate in #1 the reaction would go SN1 which would mean that you would get a lot of
by-products but you would end up getting more product also (SN1 major, E1 minor).
7) Using any compound of two carbons or less, synthesize methyl ethyl ketone (2
butanone).
OMgCl
C
C
C-C-MgCl
O
C
C
C
OH
H2O
C
C
C
C
O
PCC
C
C
C
C
C
Extra Credit - Esters are usually made by reacting an alcohol with an acid but they do not
have to be. It is possible to make an ester using a ketone and acid instead. Please give the
mechanism for the formation of the following ester in a base;
O
O
O
C
Na O H Ca t a l y s t
C C C + C C
C C O C C
+ H2O
OH
O
O
C
OH
C
O
-
C
C
C
C
-
O
C
C
C
O
O
C
C
-
OH
O
C
+ H2O
H2O
O
H2O + OH + C
C
O
O
C
C
C
C
C
OH H
O
C
C
C
H
H
-
+ OH