Chemistry 222 Exam 1 - ANSWERS February 11, 2010

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O NH N N H H X O H N N N H the tropylium anion X X X

1. (7 points) Place an X in the box below any aromatic molecule.

*I accepted both yes/no for rst O molecule

2. (7 points) Indicate the favored position of nitration for each of the following aromatic molecules by circling the appropriate carbon. Be sure to choose only a single carbon. I accepted any of the following indicated carbons.
OH Br OHC

O O

CH3

NO2

3. (6 points) True (T) or False (F)? F The meta-bromination of nitrobenzene will proceed at a faster rate than bromination of benzene. F !3 of benzene has two nodes. F The best fat for making soap comes from the Peruvian Pishtaco. F The pKa values needed to assess the leaving group ability of a neutral amide vs. an ester are 10 and 25 respectively. F Fischer esterification is possible in both acid and base. T Oleic acid is a liquid at room temperature. 4. (5 points) Use a Frost circle to draw the relative energies of the cyclopentadienyl cation. Show the occupancy of each of these molecular orbitals. Include the following labels on your diagram: bonding, antibonding, and nonbonding.

antibonding nonbonding bonding E

5. (20 points) Provide the major product (or missing reagents) for the following conversions. Be sure to indicate stereochemistry when necessary.
CH3 HNO3 H2SO4 CH3 + NO2 O2N NO2 CH3

Cl H3C

NaNH2 NH3 H3C

NH2 + H3C NH2

Benzyne intermediate

O KMnO4 H+ OH

O Br

1. benzene, 1.7 equiv AlBr3 2. H2O

O N2H4, KOH, !

O OH

CH3OH H+

O OCH3

O O CH3

1. 2 equiv. CH3MgBr 2. H2O

OH CH3 CH3

F + H3C Br AlBr3

F +

F
Friedel-Crafts alkylation (with rearrangement of incipient carbocation)

N C

H2O, H3O+

CO2H

O H3C O

O CH3

H2O H3C

O OH

6. (8 points) Provide the correct final product for each short synthetic transformation below.

H3C

CH

1. NaNH2 2. CH3Br H3C C

CH3

H2, Lindlar's catalyst CH3

CH3

NBS, h! CH3 or

Br

Mg, ether CH3

MgBr

1. O 2. H2O CH3

OH Br

CH3

EtBr, AlBr3

Cl2, AlCl3 Cl

+ Cl

Li, ether Li

1. 2. H2O

O PBr3 OH Br NaOEt, EtOH

7. (10 points) Provide the second product and the correct arrow-formalism mechanism for the following transformation.
O H3C N CH3 CH3 H2O, H+ H3C O OH + H H CH3 N CH3 H3C H O OH H CH3 N CH3

other product

O H3C OH2

H N CH3 H3C H OH2

OH N O CH3 H CH3 H3C

OH

H+ H3C

OH H N OH CH3 CH3

CH3

CH3 N OH CH3

8. (5 points) Draw the complete reaction coordinate for base-promoted ester hydrolysis.

energy

"irreversible" deprotonation of carboxylic acid (pKa = 5)

9. (9 points) Provide a viable synthesis for the following transformation. There are many possible syntheses. Try this problem again for some more practice. Here is one:
OH H3O+ CrO3 O MgBr HO 1. Hg(OAc)2, H2O 2. NaBH4
*or acid-catalyzed hydration, but rearrangement is a big issue!

1.

2. H2O, H+

HO

OH

CrO3

HO

1. TsCl 2. NaOEt, EtOH

O CH3 *formation of conjugated ! system is favored

*no worry of oxidizing the other 3 alcohol

Some of you used NBS/h! to place a Br next to the C=O group. You then did an E2 reaction to form the alkene pi bond. This acutally does work and was good thinking on your part. You had never seen NBS used in this way, but it can add a halogen next to a C=O (on the more substituted carbon in this case).
Br HBr Mg, ether MgBr O CH3 1. 2. H2O OH CrO3 O

NBS/h!

Br

O NaOEt CH3 EtOH

O CH3

*After Chapter 17 and 18, you will have much easier ways to answer this synthesis.

Lignin Degradation in Paper Production (alkaline pulp processing)

J. of Org. Chem. 1997, 62, 7885-7887

With funding from the U.S. Department of Agriculture, chemists at Mississippi State University have studied some of the chemistry involved in paper production. We will investigate the alkaline pulping process. The reaction of wood (sans bark) with sodium hydroxide allows for the separation of the lignin from the cellulose bers. Different kinds of papers have different ratios of lignin to cellulose. Higher quality papers will contain a higher proportion of cellulose. It is also (you may recall your kindergarten paper that was grey with visible wood chips).

O OMe O OMe HO HO O OMe lignin polymer

We are going to concentrate only on the separation of lignin from the wood chips in the pulping process. Fisher and coworkers are investigating the cleavage reactions of the lignin molecules. They write: The major interunit bond in lignin is a !-O-4 link, an ether linkage joining the !-carbon of the side chain of one phenylpropane lignin unit with the phenolic oxygen of a second lignin unit. The hydrolysis of this type of nonphenolic lignin ether linkage is believed to be the rate-limiting step in the bulk-phase alkaline hydrolysis of wood chips to pulp. We have conducted structure-reactivity studies on oxidativecleavage reactions and alkaline hydrolysis reactions of various !-O-4 lignin models. During the latter studies we observed that lignin model compound 1 underwent an unusual base-catalyzed, roomtemperature rearrangement reaction to 4 (containing an "-O-4 linkage). This rearrangement can be classied as either a 1,4-oxygen to oxygen aryl migration or an internal nucleophilic aromatic substitution reaction. We report here mechanistic studies on this rearrangement.

OH ! MeO OMe 1 O "

OMe HO CHO MeO

MeO O OH 4 OMe

CHO

Answer the following questions based on all provided information.

10.(12 points) To summarize and translate the above information from Fisher: This rearrangement is either an epoxide mechanism or a nucleophilic aromatic substitution. In each space below provide a full arrowformalism mechanism for each possibility.

I highlighted an important sentence from the Fisher article for answering the nucleophilic aromatic substitution mechanism. The key word is internal. You must show an intramolecular nucleophilic aromatic substitution reaction.
...or an internal nucleophilic aromatic substitution reaction.

MeO

OMe
resonance-stabilized carbanion intermediate

*O
! MeO OMe

H O "

OMe

*O
O CHO MeO OMe

OMe

* O
CHO O

OMe

CHO

nucleophilic aromatic substitution (intramolecular)

MeO

CHO

MeO

CHO

* = isotopic label (

18O)

*O
MeO OMe

OH MeO

*O

H OH

OMe

MeO

CHO

*O
O MeO OMe

OMe

*O
OMe CHO MeO OMe O MeO CHO
good leaving group

O O

H OH OMe

epoxide mechanism
intramolecular SN2

MeO O OH

CHO

MeO OMe

This unusual epoxide mechanism cannot be disregarded out of hand. Some would like to disregard such a proposal since the rearrangement would require a basic epoxide opening at the more substituted carbon. This is not as bad as it may look though, since the aromatic ring is providing signicant electron-donation to the more substituted carbon. The researchers found that this mechanism is not operative, but it must be considered.
11.(6 points) How does the presence of a single 18O isotopic label in the starting material allow you to distinguish between the two possible mechanisms. Explain clearly.

* = isotopic label ( * OH
! MeO "

18O)

OMe O CHO

"

OMe

See mechanistic drawings for #10 to follow the isotopically labeled oxygen. You can see where the label is in the product to help determine the correct mechanism. The researchers used 17O NMR and 18O mass spectrometry to follow the label. They found that the mechanism was, indeed, the nucleophilic aromatic substitution since they did not nd any of the 18O label in the beta hydroxyl group (epoxide pathway).

12. (5 points) Do you expect the following lignin analog to have a faster or slower rate of rearrangement? Explain clearly with a few words and any important structures. Slower, due to less stabilization of the carbanion intermediate.
OH O vs. MeO OMe CHO MeO OMe CHO OMe OH O OMe

R O O

R OMe O O

OMe

H O

R O O

R OMe O O

OMe

R O H O O

OMe

H O

R R O O O OMe O

OMe

There is additional resonance stabilization of the carbanion intermediate due to the location of the CHO aldehyde group in this isomer

H O

Notice that the () charge can never be placed on the C that bonds to the CHO group.

13. (4 points) Fisher synthesized a number of different lignin analogs. Below are two phenolic lignin precursors. Predict the pKa of each molecule and briey explain your two values.
OH OH

HO OMe A

HO B

OMe

Phenol has a pKa of 10. That is the starting point for any analysis since A and B are substituted phenols. The phenol proton is the most acidic in each molecule. The only difference beteen A and B is the location of the methoxy group (OMe). It is either ortho to the OH group in A and meta to the important OH group in B. The pKa should be a little bit higher than 10 since there are only EDGs attached to the benzene ring. EDGs will destabilize the conjugate base and produce a pKa >10. A should have a slightly higher pKa than B since the () charge of the conjugate base can be placed on the carbon that is directly connected to the OMe group.
OH OH OH vs. OMe B OH OH

O OMe A

O Bad

OMe

OMe

OMe

So, a good prediction for pKa values? A = 13 and B = 12.

Bonus (2 points) - This Spring is an exciting time for the Weinschenks. March 25th is the due date for the birth of my rst child (a son)! Predict his name. Hint: No one in either section of Orgo has this name. You will receive half credit if you get his
middle name.

TBA

Since you will not be able to receive the above bonus points until the birth, you may also attempt the following bonus for immediate reward. A description of a chemical reaction: Hoffman Elimination (OFF + MAN + A LIMB + NATION) One student got this bonus. Quite impressive.