July 2, 1998
1. For the following compounds, provide a name where a
structure is given or provide a structure where a name is given.
IUPAC names are always acceptable, common trivial names are also
acceptable. (12 points)
Answer: a four membered ring with a ketone functionality at C1.
AT C3 (the corner opposite the carbonyl), an aldehyde (a methanoyl
group) is the substituent.
Answer: A ketone with an ethyl group on one side of the carbonyl
and a 2-nitrophenyl group on the other.
2. Propose a synthetic route to each of the following
compounds, beginning with benzene and using any other organic
or inorganic reagents as required. (15 points)
Answer: Freiedel-Crafts acylation of benzene gives propanoylbenzene.
The acyl group is a meta director, so nitration gives the 3-propanoyl
nitrobenzene. Reduction of the nitro group gives the 3-propanoyl
aniline. Diazotization with sodium nitrite in sulfuric acid gives
the diazonium bisulfate. Sandmeyer reaction with cuprous oxide
(Cu2O) with cuprate ion (Cu2+) in water
gives the 3-propanoyl phenol. Alkylation of the phenol with iodoethane
gives 3-propanoyl ethoxybenzene as shown. (Note: technically,
one may need to protect the alkanoyl group during the reduction
of the nitro compound. This can be done using a cyclic ketal
which is removed under acidic hydrolysis.)
Answer: This phenol is most easily made by nucleophilic substitution.
Chlorination of benzene with Cl2 and FeCl3
(or bromination with Br2 and FeBr3) gives
chlorobenzene (or bromobenzene). The chloro group is an ortho-para
director and so after two nitrations the product is 2,4-dinitrochlorobenzene.
Nucleophilic substitution of the chloride with hydroxide gives
the 2,4-dinitrophenol as shown.
3. For the following compounds, order them by increasing
acidity (i.e., least acidic on the left and most acidic on the
right). (10 points)
4. Provide a detailed, step-by-step mechanism for the
following transformation. Show all steps explicitly, including
all protonation and deprotoanation steps. (18 points)
Answer: The first step of the mechanism is the protonation of
the carbonyl. In the second step, the resulting carbocation reacts
with the nucleophilic nitrogen of hydroxylamine. In the third
step, the product of the nucleophilic attack is deprotonated on
nitrogen. In the fourth step, the hydroxyl group of the resulting
product is protonated to make a good leaving group, water. In
the fifth step, the water departs to generate a new carbocation
(with an NHOH substituent). In the sixth and final step, this
carbocation is deprotonated to generate the product oxime.
5. Complete the following reaction sequences, providing
starting materials, products, or reagents as required. (30 points)
Answer: a Wittig reaction. The products are the alkene (2-methyl-1-butene)
and triphenylphosphine oxide.
Answer: An aldol condensation. The product is the 2-methyl-3-hydroxypentanal
or (if dehydration is spontaneous) the 2-methyl-2-pentenal).
Answer: Cyanohydrin formation. The product is benzaldehyde cyanohydrin.
Answer: Acetal formation. The products are ethanal diethyl acetal
Answer: The first two reagents add across the carbonyl to give
4-methyl-2-pentanol. The third reagent is an oxidant that takes
this secondary alcohol to 4-methyl-2-pentanone.
6. Answer the following questions about the aldol reaction. (15 points)
a) Mixed aldol reactions generally are not synthetically useful. Why?
b) Which of the following would be exceptions to this rule, i.e. aldehydes that can be used as one component in a mixed aldol reaction: butanal, methanal, benzaldehyde, and 1-methanoylcyclohexane?
c) 3-Methyl-2-cyclopentenone can be prepared by a reaction related
to the aldol reaction from an acyclic dione. What is this dione?
a) They generate a mixture of products, if both aldehydes can act as both enolate nucleophile and carbonyl substrate.
b) The exceptions are the aldehydes with no alpha hydrogens: methanal and benzaldehyde.
c) (Note that the name has been corrected in the key: 3-methyl-2-cyclopentenone). The precursor is 2,5-hexanedione.