NAME (print): ______________________________________________________________

TA:_____________________ Section Day:_________________ Section Time:__________

Take a few moments to look over the exam. Do problems first with which you are most

comfortable. Important points and unknowns are in bold type. Do all preliminary work on

the worksheets. The worksheets will not be graded. There is a Periodic Table on page 16 of the

exam. The exam is 2 to 2-1/2 hours with 1/2 hour for review. STOP writing when you are

asked to do so. Put your name on the cover sheet and subsequent pages where indicated.

Bonus: What is the name of the compound whose structure is on the front of your textbook?

You are to do either 1a or 1b, not both of them.

REMEMBER: Neatness is to your advantage. Have a GREAT winter break! Best of

Luck in Chem. 221b!

1. (35 pts) Mechanism __________ 2. (25 pts ) Reactions I __________ 3. (25 pts) Reactions II __________ 4. (32 pts) Potpourri __________ 5. (30 pts) Radicals __________ 6. (30 pts) NMR __________ 7. (30 pts) Structure Proof __________ 8. (43 pts) Synthesis/NMR __________ 9. (5 pts) Bonus __________ ___________________________________ Total

Let's hear it for cyclohexane!!!

1a) Mechanism (35 pts.): You are to do either 1a or 1b, not both. Mark the box in

the left margin for 1a to be graded.

Nature employs the SN2 reaction twice in the formation of -OCH3 and -NCH3

groups where oxygen and nitrogen, respectively, are nucleophiles. Adenosine triphosphate

(ATP) 1 reacts with the amino acid methionine 2 to form S-adenosyl methionine (SAM) 3,

Nature's methylating agent. For instance, SAM serves as a methylating agent to convert

dihydroxy aldehyde 4, acting as a nucleophile, into vanillin 5.

a) (5 pts.)Why is the triphosphate group (or a phosphate group for that matter) in 1 a

good leaving group?

b) (5 pts.)What is the configuration (R,S) at the carbon designated by the arrow in

methionine 2 (Fischer projection)? ______

The mechanism of this reaction sequence has been unraveled using isotopic labeling.

Assume that the bold hydrogen at C5 in ATP 1 is a deuterium atom instead of hydrogen.

Answer the following questions.

c) (5 pts.)What is the configuration (R,S) at C5 in deuterium labeled ATP 1 ? _____

d) (5 pts.)What is the configuration (R,S) at C5 in deuterium labeled SAM 3? _____

Assume that labeled methionine 2 is prepared such that the -SCH3 group is now a chiral

methyl group -SC(HDT) of the R-configuration containing hydrogen, deuterium and

tritium.

e) (5 pts.) Draw this configuration using the template below.

f) (5 pts.) What is this configuration in the labeled methyl group in SAM 3? ______

g) (5 pts.) Draw the configuration of the labeled methyl group in vanillin 5 using the

template shown below. What is its configuration? ________

1b) Mechanism (35 pts): You are to do either 1a or 1b, not both. Mark the

box in the left margin for 1b to be graded.

During the term we studied the oxidation of alcohols with Cr(VI) reagents. In

particular, the use of PCC to oxidize primary alcohols to aldehydes was addressed.

The sequence of reactions in equations a - c is a variation of the so-called Swern

oxidation, which accomplishes the same goal. Your counterparts at "that other

institution" were asked questions about this series of reactions during the past term.

The questions in italics were asked of them.

a) (5 pts.) Provide an alternative to HBr for the conversion of alcohol 1 to

bromide 2 in equation (a). [We have discussed two alternative methods]

b) (5 pts.) Suggest a mechanism for the reaction of dimethyl sulfoxide 4 to form

sulfoxonium salt 5 in equation (b). Use the curved arrow formalism. [The

polarized S-O bond in 4 is the same as S=O.

c) (5 pts.) Classify the reaction in equation (b): (SN1, SN2, E2, E1, addition,

etc.)

d) (5 pts.) What is the oxidizing agent? What is the reduction product?

They were asked to provide a mechanism for the decomposition of the

sulfoxonium salt 5 formed in equation (b). They were given as the correct answer

(after the exam) the E2 mechanism shown in equation (c). However, the

mechanism shown below (equation d) is equally plausible. In this mechanism,

intermediate 10 is formed. The same reactants 5 and 6 give the same products 7,

8, and 9 in both mechanisms! To decide between equation (c) or equation (d) as

the correct mechanism, dimethyl sulfoxide 4 [(CD3)2S=O] having deuterium (six

of them) in place of hydrogen was used.

• Here are the facts!

When totally deuterated dimethyl sulfoxide 4 [(CD3)2S=O] is used to form

sulfonium salt 5, its reaction (i.e., 5) with triethylamine 6 gives ammonium salt 7

[(C2H5)3ND+ Br-] containing one deuterium atom and dimethyl sulfide 9

[CD2HSCD3] containing only five of the original six deuterium atoms that were

present in the (CD3)2S=O.

e) (15 pts.) Which of the two mechanisms does the data support? [Hint:

Compare the location of the deuterium atoms in equation (c) and (d).]

Illustrate and explain.

2) Reactions I (25 pts.) Provide the expected major product in five of the following six

reactions. Do only five. If you did six, put a big "X" through the one you want

excluded. Pay attention to stereochemistry.

3) Reactions II (25 pts.): Provide the reagents in five of the following six reactions. Do

only five. If you did six, put a big "X" through the one you want excluded. Pay

attention to stereochemistry. Each reaction requires the number of steps shown.

(There may be alternatives.) Place the reagents by the arrows.

4) Potpourri (32 pts.): Circle the correct answer in each of the following:

a) The compound whose conjugate base will deprotonate only two of the other

compounds. [Hydrogens are in bold type.]

C2H2 NH3 (CH3)2CHOH NH4Cl CH3CO2H

b) The compound with the shortest bond (bold):

c) The best estimate of the rotational barrier (kcal/mol) about the C-C bond in ethane.

0.9 ---------3.0 ----------3.3 ----------------3.9------------------- 5.0

d) The hybridization of the central carbon of allene (CH2=C=CH2).

s ----------p------------- sp---------------- sp2----------------sp3------------------ p

e) The heat of formation of n-butane is -30 kcal/mol. The heat of hydrogenation (2 moles)

of 1-butyne is -70 kcal/mol. The best estimate for the heat of formation (kcal/mol) of 1-

butyne is:

-100 ..............70 ...............-45.................... -40............... +39.............. +30

f) A one hydrogen triplet appears in a 1H NMR spectrum with J = 6.0 Hz. The three

peaks appear at d 0.9, 1.0, and 1.1. What is the frequency (MHz) of the spectrometer?

indeterminate .............500 ..............100............... 600.................. 60

g) The value of DGo (kcal/mol) for the equilibrium between the two chair conformations

of trans-1,4-dimethylcyclohexane (gauche butane interaction: 0.9 kcal/mol).

0------------0.9------------- 1.8---------------- 3.6 ------------5.0 ---------------none of these

h) The compound with the greatest number of singlets in its broad band proton

decoupled 13C NMR spectrum.

5) Radicals (30 pts.): The free radical chain chlorination of cyclohexane affords

chlorocyclohexane. Answer the following questions.

a) (10 pts) Write the propagation steps?

propagation step 1 --->

propagation step 2 --->

b) (10 pts) Determine the CH bond dissociation energy (BDE) for cyclohexane, the

BDE for the CCl bond in chlorocyclohexane, and the DHo for propagation step 2.

Show work. [DHo (overall rxn.) = -30 kcal/mol; DHo (propagation step 1) = -8

kcal/mol; BDE HCl = 103 kcal/mol; BDE Cl2 = 58 kcal/mol]

d) (10 pts) Provide an energy diagram for this reaction. Include the three values of

DHo and obey the Hammond postulate.

6) NMR (30 pts.): An unknown compound A (C8H16) reacts with O3 followed by zinc

reduction to give two compounds, B and C. Compound B has a singlet (d 2.07) in its 1H

NMR spectrum and two singlets (one singlet is weak; d 204) in its broad band proton

decoupled 13C NMR spectrum. The 1H NMR spectrum of C displays the following data

(d values are estimated): d 2.5 (quartet) and 1.2 (triplet). The integration of the two signals

in the spectrum of C is in a ratio of 2:3 (quartet:triplet). What are the structures of A, B,

and C? Explain.

7) Structure Proof (30 pts.): (S)-(+)-Limonene, (C10H16, [a]D +124o) is a terpene found in

the rind of lemons and oranges. Ozonolysis of (S)-(+)-limonene followed by treatment

with dimethyl sulfide results in the isolation of 1. Hydrogenation of limonene gives cis-

and trans-1-isopropyl-4-methylcyclohexane.

a) ( 5pts.) How many degrees of unsaturation are present in limonene?

b) ( 5pts.) What important information is gained from the hydrogenation experiment?

c) (5 pts.) What is the other product of ozonolysis?

d) (5 pts.) Draw (S)-(+)-limonene.

e) (10 pts.) (S)-(+)-Limonene reacts with 2 equivalents of HBr in Markovnikov

fashion to give two optically inactive compounds C10H18Br2. Draw their

structures and explain briefly. {Hint: Think about the hydrogenation

experiment.]

8) Synthesis (43 pts): Gainfully employed in a laboratory during the summer, a graduate of

Chem 220a is given the challenge of synthesizing disparlure (1), the optically-active sex

attractant of the female gypsy moth. She uses 5-methyl-1-hexanol (3), part of oleic acid 2

for the n-alkane chain, and compounds with two or fewer carbon atoms as her sources of

carbon. All other reagents are available to her.

a) (25 pts) Show her synthetic plan.

b) (10 pts.) She understands why her starting alcohol 3 (C7H16O) contains only six

singlets in its broad band proton decoupled 13C NMR spectrum, and she fully expects to

see all nineteen carbons as unique singlets in the 13C spectrum of her synthetic disparlure

1. [Note: There is no fortuitous overlap of singlets]. Explain her reasoning.

c) (8 pts.) The 1 H and 13C NMR spectra of her synthetic material were identical to the

corresponding spectra of the pheromone isolated from the female gypsy moth. What

measurement that she took showed a difference between the synthetic and natural material?

Why?

9) Bonus (5 pts) What is the name of the compound whose structure is on the front of your

textbook?