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Chemistry 303 Fall, 2011

FINAL EXAMINATION

1:30 PM, January 18TH, 2012

Duration: 20 minutes reading and then 3.0 hr to write Name___________________________________________________________ (Official Name) This is an “open book” examination; you may use anything that is not alive or connected to the Web.

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.

If you do not know a structure and need to write a mechanism, write a general mechanism for partial credit.

You need not draw transition states as part of a mechanism unless expressly instructed to do so.

USE THE ARROW FORMALISM CAREFULLY FOR ALL MECHANISMS. SHOW ALL INTERMEDIATES.

BE SURE TO INCLUDE ALL FORMAL CHARGES.

Write only in the space provided for each question. Score: p2___________/ 10 p3___________/ 10 p4___________/ 18 p5___________/ 18 p6___________/ 15 p7___________/ 12 Lab question _________/26 p8___________/ 6 p9___________/ 14 p10__________/ 10 p11__________/ 12 p12__________/ 15 p13__________/ 14 p14__________/ 30 p15__________/ 16 Lecture Total: /200 There are 19 pages in this exam; please check now to be sure you have a complete set. The last page is Table 3.2 from the text, related cyclohexane conformational data, and a glossary of definitions. Pledge:_________________________________________________________________________________

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1. Fumaric acid is an intermediate in the Krebs cycle and is involved in the production of energy in the form of ATP from the breakdown of carbohydrates, fats, and proteins. Fumaric acid and its closely related isomer maleic acid have several unique properties that significantly alter their relative properties in living organisms and in the laboratory. For example, consider the aqueous pKa values for the two compounds.

(a) (5 pts) Provide the single best reason why the most acidic proton (pKa1) on maleic acid is approximately 12.5 times more acidic than the corresponding proton on fumaric acid. (b) (5 pts) Interestingly, the second proton to be deprotonated on maleic acid (pKa2) is approximately 70 times less acidic than the corresponding second proton on fumaric acid. Provide the single best reason to explain this data.

CO2HHO2C HO2CCO2H

fumaric acid

pKa1: 3.02pKa2: 4.38

maleic acid

pKa1: 1.92pKa2: 6.23

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2. (5 pts) (a) Label the following molecules in order of basicity (most, least, intermediate), and defend your choice. You must draw pictures to receive credit.

(b) (5 pts) Now consider molecules A and B. Contrary to what you might expect at first glance, the basicity of A is approximately the same as the basicity of B. Provide the single best reason why. Explain your choice with carefully drawn pictures.

O2N

NMe2

Me

NMe2

MeO

NMe2

O2N

t-BuNMe2

O2N

t-BuNMe2

A B

O2N

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3. (18 pts) For each of the following pairs of reactions, (i) draw the product(s) of each reaction and (ii) circle which member of the pair would be FASTER. (iii) Explain briefly the most important reason for your choice.

O

MeMe

Br

MeMe

Br

Me

(a) AgNO3

EtOH

AgNO3

EtOH

t-Bu

t-Bu Cl

Cl

NaI

acetone

NaI

acetone

(b)

(c) Br

Br

OH

NaH

Et2O(0.1M)

NaH

Et2O(0.1M)

HO

Me

Me

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4. Consider the following transformations of compound C.

(a) (6 pts) Predict the structure of D and draw the best mechanism for step (1) of its formation. Include a carefully rendered drawing of the rate-determining transition state of the reaction. (b) (8 pts) Predict the structure of E that is consistent with the IR data provided, and indicate the single best mechanism for its formation. (c) (4 pts) Compounds D and E were both treated with MnO2, but only one of the two underwent reaction. Predict which compound reacted with MnO2; draw the structure of the resulting product; and briefly rationalize your choice.

Ph H2SO4

H2O

1. BH3, Et2O

2. H2O2, NaOHD: C11H14O

E: C11H14O

C

select IR data: 3432, 3083, 1644, 1610 (phenyl) cm–1

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5. Consider the following reaction in the gas phase and the provided data:

(a) (2 pts) Draw the product G in the box provided above. (b) (2 pts) Identify the nucleophile and the electrophile of the reaction. (c) (4 pts) Carefully draw the orbitals corresponding to the HOMO of the nucleophile and LUMO of the electrophile. (d) (3 pts) Which of the thermodynamic terms above favors this reaction going toward G? (e) (4 pts) The equilibrium constant for this reaction in aqueous solution is much larger than the one provided for the gas phase. How can you account for this fact?

!H0 = +6.36 Kcal/mol!S0= +0.00115 Kcal/K*mol

T = 25°C!G0 = +6.02Kcal/mol

Keq = 3.85*10–5

Cl ClMe

F

G

NMeMe

Me

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(f) (12 pts) On one plot, draw reaction coordinate diagrams for the gas phase and aqueous reactions. Be sure that your diagrams account for the relative energies of the starting materials, products, and activation energies between the two conditions. Label !Go

gas, !G‡gas, !Go

aq and !G‡aq.

reaction coordinate

pote

ntia

l ene

rgy

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6. Consider the following data regarding the reactions depicted below:

(a) (2 pts) What type of isomers are H and I? (b) (4 pts) What elimination mechanism is most likely for reactions (i) and (ii)? Draw the curved arrow mechanism that accounts for the product generated in (i). Note: you do not need to draw a 3-dimensional picture of H for your mechanism.

MeMe

Br

MeMe MeMe

MeMe

Br

MeMe MeMe

Me Me Me

100% 0%

Me Me Me

25% 75%

NaOEt

EtOH

NaOEt

EtOH(i)

(ii)

H

I

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(c) (12 pts) Draw the chair conformations of H and of I (4 total). Circle the lowest energy chair conformation for each molecule and calculate how much lower in energy each is relative to the higher energy form (note: the back page of the exam has useful data for doing this). Show your work and if necessary, identify any ambiguities in your estimate. (d) (2 pts) Why does reaction (i) give only one product? Explain your answer using 3-dimensional pictures.

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(e) (4 pts) Why does reaction (ii) favor the indicated product? Explain your answer using 3-dimensional pictures. (f) (6 pts) Assign the 1H NMR spectra below to the two products of reactions (i) and (ii). Describe one diagnostic feature of the spectra that justifies your answer.

01234567PPM

0123456PPM

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7. In 1990 the Sharpless lab at MIT devised an elegant synthesis of L-hexose derivatives beginning from the allylic alcohol J shown below. (a) (4 pts) Draw the product (K) of epoxidation of J with mCPBA and indicate how many stereoisomers are possible for the product.

(b) (8 pts) If K is subjected to a reaction containing a sulfur nucleophile, what's known as a Payne reaction can occur. The product of the Payne reaction is depicted below. Provide a mechanism for the formation of product L.

OO

MeMe

OH

(+/–)-J

K

mCPBA

OO

MeMe

SPh

NaSPhNaOH

H2O, t-BuOHOH

OHK

L

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8. The following reaction sequence can be used to provide P from M.

(a) (4 pts) Draw the structure of N and describe the two most diagnostic features of N that would show up in an IR spectrum (not the fingerprint region). (b) (4 pts) Draw the structure of O. About where would you expect the most downfield (highest ppm) signal to be in the 1H NMR spectrum of O? (c) (2 pts) Label all of the stereocenters in P as (R) or (S) (d) (5 pts) Draw the structure of P in its lowest energy chair form (make sure that you draw the correct enantiomer of P).

I

NaOH 1. O3

2. H2O2

O OH

H

M

N O

P

one step

(next semester)

formula: C10H18Oacetone

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9. Labeling molecules with unnatural isotopes can change their spectral properties. Consider the following pair of molecules, one of which has ONLY 12C carbons (Q), and the other of which has TWO 13C labeled carbons (R) and ONE 12C carbon.

(a) (6 pts) If the molecular ion of Q is set to 100% in the mass spectrum, what percentage is M+1 for Q? M+2? Would the mass spectrum be different in a predictable way in R? If so, how? (b) (4 pts) Q has an absorption peak at 1637 cm–1 in the IR. What functional group does this correspond to? Would this stretching frequency shift in a predictable way for R? If so, how? Briefly explain your answer. For part (c), use the labeling scheme Cx-Cz shown below:

(c) (4 pts) How many signals would you observe in the proton-decoupled 13C NMR spectrum for Q? What splitting patterns would they have and why? How many signals would you observe in the proton-decoupled 13C NMR spectrum for R? What splitting patterns would they have and why?

H312C12C

12C

Br

H

H

H312C13C

13C

Br

H

HQ R

CxH3Cy

Cz

Br

H

H

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10. (30 pts) Provide the necessary reagents to convert 1-methylcyclohexene (S) into the target compounds T–Y. (Hint: More than one step may be required in some of the conversions.)

Me Br

T (racemic)

Me OH

(a)

S

OH

U (racemic)

Me Br

(b) S

MeOCH3

V (racemic)

(c) S

OH

W (racemic)

Me OH

(d) S

OH

X (racemic)

Me OH

(e) S

O

Y (racemic)

(f) S

Me

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11. Caryophyllene is obtained from the oil of cloves. When it is treated with aqueous acid, two products are obtained, caryolanol and clovene.

(a) (8 pts) Draw the best arrow-pushing mechanism for the formation of caryolanol (you do not need to account for the stereochemical outcome of the reaction). (b) (8 pts) Draw the best arrow-pushing mechanism for the formation of clovene (you do not need to account for the stereochemical outcome of the reaction).

H

H

MeMe Me

HH2SO4

H

H

MeMe Me

HO

Me

MeMe H

clovenecaryolanolcaryophyllene

H2O

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Lab-Related Question (26 pts)

Bromination of “butene” isomers (C4H8) 1 and 2 gives dibromides 3 and 4, respectively.

Proton-decoupled 13C NMR spectra of “butene” isomers 1 and 2 and the 1H NMR spectra of dibromides 3 and 4 are summarized below:

“Butene” 1 proton-decoupled 13C NMR (CDCl3): " 25.8, 112.1, 141.8 “Butene” 2 proton-decoupled 13C NMR (CDCl3): " 14.0, 26.7, 116.4, 134.3 Dibromide 3 1H NMR (CDCl3): " 1.87 (s, 3H), 3.86 (s, 1H) Dibromide 4 1H NMR (CDCl3): " 1.08 (t, J = 7 Hz, 3H), 1.75-1.91 (m, 1H), 2.12-2.26 (m, 1H), 3.63 (t, J = 10 Hz, 1H), 3.84 (dd, J = 10 Hz, J = 4.5 Hz, 1H), 4.10-4.20 (m, 1H) (a) (4 pts) Deduce the structures of “butene” isomers 1 and 2. Indicate how the proton-decoupled 13C NMR spectra of “butenes” 1 and 2 support your structural assignments. (Hint: There are only four possible “butene” isomers. Draw the four possible isomers.)

1PyHBr3

CH2Cl2 0 °C

3

2PyHBr3

CH2Cl2 0 °C

4

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(b) (3 pts) Deduce the structure of dibromide 3. Draw your proposed structure for dibromide 3, and label the hydrogens on your proposed structure. Support your structural assignment by assigning the 1H NMR signals to the appropriate hydrogens. (c) You should be able to deduce the structure of dibromide 4, based on your proposed structure of “butene” 2. (There are no rearrangements here – THINK SIMPLE!) Of course, we eventually want you to assign all of the 1H NMR signals for dibromide 4 and to explain the splitting patterns. However, we suspect that you may find the 1H NMR spectrum of dibromide 4 more complicated than expected. So, a little guidance is in order. (Hint: Chemical shift calculations are not required, but may prove helpful for your spectral analyses.) (1) (1 pt) Draw the structure for dibromide 4, based on your proposed structure for “butene” 2. (2) (10 pts) Draw the lowest energy staggered Newman projection looking down the carbon-carbon bond, connecting

the two bromine-substituted carbon atoms of dibromide 4. Label the hydrogens on these two carbon atoms. Now, assign the 1H NMR signals to these labeled hydrogens and explain the observed splitting patterns. Does the magnitude of the observed coupling constants support your lowest energy conformational assignment? Explain.

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(3) (4 pts) Please explain why the multiplets at " 1.75-1.91 and 2.12-2.26 ppm appear as separate 1H multiplets, rather than as one 2H multiplet. Which two protons in dibromide 4 give rise to these two multiplets?

(4) (2 pts) Please assign the remaining signal in the 1H NMR spectrum of dibromide 4, and explain the observed splitting pattern. Don’t forget the label(s).

(5) (2 pts) The signal at " 4.10-4.20 ppm is reported simply as a multiplet (“m”), although perhaps “mess” might

be a more apt description. The proton, giving rise to this mutiplet, should already be labeled in your Newman Projection from Part 2 above. What should be the actual multiplicity of this signal (e.g., dd, td, etc.)? Explain.

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Typical gauche interactions: 0.9 kcal/mol Typical 1,3-diaxial interactions: approx 2.0 kcal/mol Glossary: Me = methyl Et = ethyl Ph = phenyl t-Bu = tert-butyl OMe = methoxy

O THF

LDA = lithium disopropylamide N

MeMe

MeMe

Li

Ts = tosylate =MeS

O

O

Me SO

MeDMSO DMF

O

H NMe2