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1Chemistry 303

fall 2001

FINAL EXAMINATION

8:30 am, January 19th, 2002

Duration: 3 hr

There will be an additional 30 min allotted for the course evaluation before the exams are collected

Name________________________________________________

Lab TA______________________________________________ [do not write Hooley]

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--WRITE SOMETHING

NOTE: write your mechanisms CAREFULLY. A good answer will require precision in the use of the arrows anddescription of spectral information. READ each question completely and carefully before answering.

  I._______/40

  II._______/18

  III._______/23

  IV._______/35

  V._______/22

  VI._______/22

 VII._______/10

VIII._______/10

  IX. ______/20

total: _______/200

There are 14 pages in this exam; the last page is a list of the common amino acids, for your convenience. You mayrip it off. Please check now to be sure you have a complete set.

EVALUATION FORMS ARE AVAILABLE IN THE FRONT OF THE ROOM. IF YOU HAVE NOTDONE SO ALREADY, PLEASE FILL ONE OUT BEFORE YOU LEAVE AND LEAVE IT HERE.

Pledge:

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I. (40 pts) For each of the following pairs of reactions, predict which will occur faster. 2Write the organic product(s) and the mechanism (not transition states) for the faster reaction and give the singlemost important reason for the difference (explain in detail).

A.Br

H

AgNO3

MeOH

BrAgNO3

MeOH

____________________________________________________________________________

Br

Br

+ NaCN

+ NaCN

CH3CN

CH3CN

B.

cont...

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H

MePh

Cl

I+ K OMe

E2

Ph

H

MePh

Cl

I + KE2

O

O

Ph

C.3

_____________________________________________________________________________

D.N

O HO-, H2O

O

O HO-, H2O

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II. (18 pts). A. (8 pts)  Draw the most likely structure for C [racemic mixture; drawboth enantiomers ofC showing clearly the configuration at the stereogenic carbon(s)]. Then draw themechanism for the formation of B (you need draw only one enantiomer of B) to illustrate the mechanism.

4

a. R2B-H b. H2O2

A

 {B}   {C} NaOH

B. (5 pts)  Draw one other stereoisomer of C (not B) and explain clearly why it is NOT formed. Isthis isomer related to C as:

an enantiomer? a diastereoisomer? a meso compound?

C. (5 pts)  Draw one other isomer of C which is a regioisomer and explain clearly why it is NOT formed in significant amounts.

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III. (23 pts). 5

A. (11 pts) Note the planar representation of D and consider the reaction of D to give E.  Draw on the chairtemplate the most stable conformation of D. Write the best mechanism for the formation of E. Show allintermediates, and account for the exact stereo arrangement in E.

OH

AgNO3

EtOHD

E

H

OH

Br

D

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B. (12 pts) Consider the reaction of F to give G and H.  Write the best mechanism for the formation ofG and H . Show all intermediates, and account for the formation of bothG and H . Are G and H related as being:(circle all correct answers)

6

a. enantiomers? b. diastereoisomers? c. mirror images? d. fragomers?

 

Br

AgNO3

EtOH OEt+

EtO

F  G

H

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IV. (35 pts). Imagine the conversion of H to I, an example of a simple SN2 7substitution, with inversion of configuration. The reaction does not happen spontaneously under mild conditions,but must be catalyzed.

O

OEt

H

O

H

OH

H2O

H

I

+ EtOHO

OH

HJ

(S-enantiomer)

A. (11 pts) The substitution reaction of H in water is accelerated in the presence of HCl but gives both I and J.

  1. Why does this reaction not occur easily in the absence of a catalyst?

  2. Write a mechanism for this process, showing all intermediates but not transition states, and make

clear the role of the HCl. What is the name of this mechanism? Identify the rate-determining step.

  5. Explain how your mechanism accounts for the formation of both I  and J .

  6. Are they formed in equal amounts?

  7. Why is this mechanism preferred over the simple S  N 2 in this case?

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B. Now suppose you really want to convert H to I (and not to J). You will probably need an enzyme 8

  designed for this job.  Explain in the following questions how you might produce a catalytic antibody whichwould accelerate the substitution reaction on H  to give I . You need not discuss the biology behind the creationof monoclonal antibodies. Just focus on the chemistry and what such an antibody catalyst might look like.

 Refer to the list of 20 "essential amino acids on p 14.

O

OEt

HO

H

OHH2O

H

I

+ EtOHenzyme

1. (6 pts) Show and discuss the mechanism of the process you wish to have happen, converting H  to I (no enzyme involved yet). Include the transition state for the step which determines the rate and discuss how I could be formed selectively.

2. (6 pts)  Draw your design of a real molecule which could mimic the transition state shown in part 1, and explain your choice.

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O

OEt

HO

H

OHH2O

H I

+ EtOHenzyme

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3. (6 pts) When a catalytic antibody is found, which of the the 20 "essential" amino acids might beinvolved in the active site, to provide catalysis? Explain your choice in terms of mechanism.  It seems likely thattwo amino acids might be important in the active site, each providing a different sort of catalysis.  Explain.

4. (6 pts) The catalytic antibody is a polypeptide. Please draw a representative tripeptide comprised of, for example, alanine, cysteine, and serine. Carefully show the configuration of stereogenic carbons.

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V.  (22 pts).  Note the following conversion of M to N, using the R3Sn-H as a reactant, 10

and R3Sn-SnR3 in catalytic amounts. The reaction depends on the fact that the R3Sn-SnR3 is somewhat like aperoxide, RO-OR, in that it splits to the R3Sn• radical on gentle heating. Note that the Sn-H bond in R3Sn-H isalso quite weak. Note also that if R3Sn-D (D = deuterium) is used in place of R3Sn-H, the product is O.

 

Br

+ R3Sn-HR3Sn-SnR3

CH3

R3Sn-Br+

M   N

M  + R3Sn-DC

D H

H

O

heat

same

catalytic

This process can be written as a four-step mechanism, involving an initiation step and three propagation steps.

 Draw the mechanisms for the four steps and label them as initiation or propagation steps. Your mechanism

should show clearly: (1) why the R3Sn-SnR3 is needed in only catalytic amounts and (2) exactly how O forms as

the major product from R3Sn-D.  Explain as needed.

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VI. (22 pts). Note the conversion of Q in the presence of silver ion in dichloromethane 11

solvent to give a new product, P. While useful spectral data were collected (below), the structure of P was alsosupported by the reaction wtih ozone and the usual followup treatment of the ozone intermediate. Cpn P showedno significant UV absorption; the mass spectrum showed m/z 111 (9%) and 110 (100%).

O

O

CH2

CH2CH3

CH3 AgNO3

CH2Cl2[ P ]Q +

a. O3

b. Me2SCH2

CH2

Br

(reduction)

H

a. !1.30 (2H) ___________

b. !1.71 (3H) ___________

c. ! 1.76 (3H) ___________

d. !1.82 (2H) __________

e. ! 2.01 (2H) __________

f. ! 3.82 (2H) __________

g. ! 5.44 (1H) __________

pattern pattern pattern

A. (7 pts) Consider the list of 1H NMR chemical shift and area data for Q. Assign the chemical shifts to

proton(s) in Q by labeling the structure above with letters a, b, etc. Then complete the list of data by

adding the pattern expected (splitting pattern; e.g., s, d, t, quart, quint, sext, sept, ..) for each proton or

group of equivalent protons. Ignore long range coupling. Some assignments are ambiguous; discuss if

necessary.

B. (3 pts). How many peaks are expected in the 13C NMR spectrum for Q (proton-decoupled)?

  Circle best answer: a. four b. five c. six d. seven e. eight f. nine

C. (7 pts) Give the structure for P, and explain how the following spectral data are consistent with your

structure for P:  1H NMR: ! 1.2 (2H, t, J=7Hz); 2.1 (2H, t, J=7Hz); 1.6 (s, 3H).

  13C NMR: 5 peaks

D. (5 pts). Write a mechanism for the formation of  P from Q.

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VII. (10 pts) Triphenylphosphine oxide can serve as an oxidizing agent under some 12conditions. The process occurs by our standard mechanisms. Please propose a mechanism for the followingconversion. Name the steps in the mechanism.

Br

+ Ph3P-O

triphenylphosphineoxide

  heat H

O

+ Ph3P + HBr

 _____________________________________________________________________________ 

VIII. (10 pts) Suppose you were trying to make an honest living with chemistry and needed to synthesize

compound R. Show the steps you might use to convert S into R.  For each step, list the reagents needed to

 promote that step (e.g., HCl, NaOMe, Et3N, CrO3, O3, Br2, HBr, RO-OR, NaCN, NaI, NH3, R2BH, H2O2,

MeI, etc). It sometimes helps to work backwards as well as forward in thinking about the problem.

steps?

CNS   R

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  IX. (20 pts). Consider the conversion of W to Y via the intermediate X.  Note the NMR data for Y. 13

O

H

Br

+ MeOHH

[ X ]H

H

BrOMe

OMe

YW

1 H NMR: ! 3.15 (s, 3H),

3.36 (s, 3H),

4.7 (d, J=7Hz, 1H),

5.3 (d, J=7Hz, 1H),

7.3 (m, 5H)

A. (10 pts).  Draw the most likely structure for X  and a mechanism for its formation, including the role of acid in

accelerating the formation of X . Note that the IR spectrum of X shows no strong absorption in the region 1600-

1800 cm-1 but does show a broad peak at ca 3400 cm-1.

B. (10 pts).  Draw the most likely mechanism for formation ofY  from X including the role of acid in

accelerating the process. Draw the structure ofY again here large showing all hydrogens, and indicate clearly

the chemical shift position of each. Please be sure to account for the fact that there are two singlets of 3H each

and not one singlet for 6H instead.

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HO2C NH2

H CH3

HO2C NH2

H H

HO2C NH2

H

HO2C NH2

H

HO2C NH2

H

HO2C NH2

H

HO2C N

H

H

HO2C NH2

H

HO2C NH2

H

HO2C NH2

H

OH

OH

OH

HO2C NH2

H O

NH2

HO2C NH2

H

O

NH2

HO2C NH2

HNH2

HO2C NH2

H N

NH

NH2H

HO2C NH2

H

N H

HO2C NH2

HN

N

H

HO2C NH2

H CO2H

HO2C NH2

H

HO2C NH2

H SH

HO2C NH2

HS-Me

CO2H

glycine

tyrosine

threonine

serine

proline

phenylalanine

isoleucine

leucine

valine

alanine

asparagine

glutamine

lysine

arginine

tryptophan

histidine

aspartic acid

glutamic acid

methionine

cysteine

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