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Chemistry 303

Fall 2007

THIRD EXAMINATION

8:30 AM, DECEMBER 17th, 2007

Duration: 1.33 hr

Name____________________________________________________________

Lab TA___________________________________________________________(if you do not know his/her name, give day of lab section—Not BJ, Casey, David)

This is an "open book" examination; you may use anything which is not alive.

Note: if you do not know the complete or specific answer, give a partial or general answer—

We love to give partial credit.

If there seems to be more than one good answer, explain your thinking.

If you invoke resonance delocalization as part of your answer, draw the relevant resonance structures.

If you draw a chair cyclohexane, be sure to orient the bonds carefully.

USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS

BE SURE TO INCLUDE ALL FORMAL CHARGES

IF YOU ARE ASKED TO WRITE THE PRODUCTS FROM A PROCESS INVOLVING STEREOCHEMISTRY, BE

SURE TO DRAW STEREOISOMERS CLEARLY.

Write only in the space provided for each question. 

Score:

P1___________/15 P2___________/15 P3___________/20 P4___________/25

P5___________/25 Total: /100

There are 7 pages in this exam, including the cover; please check now to be sure you have a complete set.

Pledge:_________________________________________________________________________________

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1. a. (6 points) When (S)-2-bromopropanoic acid is treated with a high concentration of sodium hydroxide, theproduct that forms is (R)-lactate.   Provide a detailed mechanism for this transformation that accounts for the stereochemistry of the product. Use clear three-dimensional drawings to show the structure of any proposed transition states.

Br

O2C

H3CHHO HO

CO2

CH3H + Br

(S)-2-bromopropanoic acid (R)-lactate

b. (9 points) Silver is a Lewis acid with an affinity for “soft" nucleophiles, such as an alkyl halide or an olefin.

When (S)-2-bromopropanoic acid is treated with silver cation and a low concentration of sodium hydroxide, (S)-

lactate is formed, as shown below.   Provide a detailed mechanism for this transformation that accounts for the 

formation of (S)-lactate under these conditions. Explicitly indicate the role of Ag +  in your proposed mechanism.

Br

O2C

H3CHHO

OH

O2C

H3CH + Ag

+  Br_

(S)-2-bromopropanoic acid (S)-lactate

Ag+

Lowconcentration

+

+

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NH2

CH3H3C  Cl

O

Cl

Et3N

HN

CH3H3C

O

ClHN

CH3H3C

O

N CH3

CH3

Et2NH

Lidocaine

2. (15 points) Lidocaine, a commercial anesthetic, is produced on ton scale every year. It can be accessedeasily in two steps from 2,6-dimethylaniline.

In the second step, the reaction proceeds at a much higher rate when a catalytic amount of sodium iodide (NaI)is added.   Using the arrow formalism, please propose a mechanism that explains this observation. Classify the expected kinetics for each step (i.e. unimolecuar, bimolecular, etc.). Clearly show the catalytic role of iodide in your mechanism.

HN

CH3H3C

O

ClHN

CH3H3C

O

N CH3

CH3

Et2NH

cat. NaI

Et2NH

fast 

slow 

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HOOH

CH3

CH3H3C

H3C

H2SO4O

CH3

CH3H3C

CH3

HOOH

Ph

HH

Ph

H2SO4O

Ph

HH

Ph

OPh

PhH

H

3. a. (8 points) When 2,3-dimethyl-2,3-butanediol is heated in the presence of a catalytic amount of acid, a multi-

step rearrangement occurs (via mechanisms that should be very familiar to you) that results in the formation of a

ketone. Using the arrow formalism, propose a mechanism for this transformation. Clearly show the catalytic role of

H + .

b. (12 points) This rerrangement is a general reaction of 1,2-diols. When 1,1-diphenyl-1,2-ethanediol is heated in

the presence of a catalytic amount of acid, two products are possible. In practice, one product forms exclusively.Using the arrow formalism, propose mechanisms by which both products can arise. Using your proposed 

mechanisms, predict which product forms exclusively, and explain BRIEFLY . Be sure to clearly show the catalytic

role of H + .

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CH3

H3C

H3C

CH3

OTsCH3

H3C

H3C

CH3

OH

CH3

H3C

H3C

CH3

1 2 3

4. When compound 1 is treated with NaOH in DMF, products 2 and 3 are formed in 36% and 27% yields, respectively,by mechanisms you have seen before.

HH

HNaOH

36 % 27%

DMF

a. (5 points) In the space provided, draw a clear, three-dimensional representation of the most stable conformationof compound 1.

b. (10 points) Using the arrow formalism, provide mechanisms to account for the formation of each product ( 2 and 3 )from compound 1. Classify each mechanism as E1, E2, S N 1, or S N 2.

CH3

H3C

H3C

CH3

OTs

1

H

Ts = S

O

O

CH3

p. 5

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CH3

H3C

H3C

CH3

OTsCH3

H3C

H3C

CH3

OH

CH3

H3C

H3CCH3

H3C

H3C

Me

1 2 3 4

 A third product, compound 4, is also formed in this reaction, in 32% yield, by a rather unusual mechanism.

CH2

OHCH3

HH

HHNaOH

36 % 27% 32%

DMF

c. (10 points) Using clear, three-dimensional drawings, provide a detailed mechanism for the transformation ofcompound 1 into compound 4.

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5. (25 points) The cyclohexene derivative shown below is a very versatile intermediate. A. Provide the single mostlikely product resulting from each of the reaction conditions shown. B. Clearly indicate the configuration of all stereogenic centers in your products and assign them as R or S using the Cahn-Ingold-Prelog system.

CH3

CH3H3C

CH3

a) O3

H3C  S

CH3

a) BH3

b) H2O2, KOH

F3C O

O

O

H

a) OsO4

b)

b) H2O

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