Chem 313 Problem Set #2, 2010
1. Using detailed mechanisms, explain how you can determine whether or not ester
saponification happens th18ugh a tetrahedral i18erm-diate (route A) or via aNdirect S 2
mechanism (route B) using O labeled hydroxide ( OH ).
Let the shaded oxygens represent O. In the first route the labeled oxygen will end up in
the acetate, and the other route it ends up in the methanol. These differences can be
2. Explain why acid catalyzed ester hydrolysis is reversible, but saponification is not.
What conditions would you use to control the output of the acid catalyzed reaction?
H 3 /H2O
H O + CH OH + H
2 CH 3 3
OH /H O
CH 3 CH 3H +
O O For saponification the reverse reaction is shown above. But recall that the pKa for acetic
acid is ~4.5 and the pKa of methanol is ~ 17. Therefore this species does not exist under
the given conditions. The thermodynamic stability of the products generates this
Under acid catalyzed conditions:
Activation of the carbonyl is similar for forward and reverse reactions. Therefore we
control equilibrium using LeChatellier’s principles. Excess H 2 drives the reaction to
the right. Removal of product (MeOH or acetic acid) also drives the reaction to the right.
3. Outline how you would prepare the following amino acids using the Gabriel synthesis:
a. b. c. d.
O O O O
NH 2 NH 2 NH 2 NH2
HO HO HO
Answers: Use the general precursor for Gabriel synthesis
a) 1)NaOEt, 2)CH Br 3ollowed by Acid workup with heat Br
b) 1) NaOEt, 2) followed by acid/heat workup.
c) 1) NaOEt, 2) Br OEtfollowed by acid/heat workup.
d) 1) NaOEt, 2) H and acid/heat workup. SN2 reaction with 1-bromoethanol will
not work here as it is an unstable species that will collapse into formaldehyde and HBr.
4. Outline how you would prepare the following amino acids stereospecifically:
a. b. c. d.
NH 2 NH2
NH NH2 HO HO
O O H
Similar to the last question except this time the reactions must be done stereospecifically
with the use of a chiral auxillary.
Refer to class notes on the generation of this species using a chiral auxillary. From here
the reaction conditions are as follows:
a) 1)Na-HMDS 2) Br OEt 3)H O 4)H /Pd
3 2 S
b)1)Na-HMDS 2) 3)H O 4)H /Pd Note: you shouldn’t use 2bromoethylthiol as
this would collapse into the thioepoxide shown above.
c) The trick here is adding two electrophiles while maintaining the correct
1)Na-HMDS 2)MeBr yields: O 3)Na-HMDS
4) 5) H 3 6)H /Pd2