Chemistry 11 Fall 2011 Examination #3 ANSWER KEY

Answer the following four free response questions. Make sure to show all your work for full credit (100 pts. total).

1. (50 pts. total) Consider the structure of Levofloxacin below, a chemotherapeutic antibiotic used to treat severe or life-threatening bacterial infections . Answer each question related to its structure. amine (tertiary) H

CH3 H3C O N

N N carboxylic acid amide HO O F alkyl halide

O O Levofloxacin

A. (7 pts.) Label the seven different functional groups in the structure above, studied in this class (although more may be present), found in Levofloxacin. If any or amines are present, determine if they are primary, secondary, or tertiary.

B. (1 pt.) How many trigonal planar atoms appear in the structure above? 11

C. (1 pt.) How many trigonal pyramidal atoms appear in the structure above? 3

D. (1 pt.) How many bent atoms appear in the structure above? 2

E. (1 pt.) How many diastereomers are possible for Levofloxacin? 0

F. (1 pt.) How many enantiomers are possible for Levofloxacin? 1

G. (1 pts.) Based on your answer to part F, does the structure above exhibit an R, S, or neither absolute configuration? S

H. (3 pts.) Does this exhibit cis/TRANS isomerism? If yes, briefly explain which is present and why? On the top alkene carbon (circled), the higher priority group is the amine; on the bottom alkene carbon, the higher priority group is the carboxylic acid, which is opposite the amine and hence trans. I. (4 pts.) For the following molecule, determine whether you would expect it to have a HIGHER or LOWER boiling point than Levofloxacin. Briefly explain your answer. Circle one for expected boiling point compared H to Levofloxacin: CH3 H3C S P HIGHER or LOWER

P P Briefly explain why: The substitution of P and S (for N and HO O O, respectively) reduces the hydrogen F bonding capability of the molecule shown, thereby lowering its expected O O boiling point.

J. (8 pts.) In pharmaceutical research, structural analogs of antibiotics are often made in order to see if they have similar biological properties. Below is a structural analog of Levofloxacin called Molecule B. F F

H3C OH CH3 N H3C OH

N N = N R" R HO O F R' Molecule B O O In the boxes below, draw the most stable and least stable chair conformations of Molecule B (you may use an abbreviated notation for extended "R" groups).

R' OH R" R" R R' N CH3 N HO F R F CH3 Least Stable Most Stable

K. (1 pt.) Is Levofloxacin expected to be polar or nonpolar? polar L. (12 pts. total; 3 pts. each) Based on your accumulated knowledge of organic to date coupled with the realization that there are multiple functional groups present in Levofloxacin, what is the expected product for each reaction below? Draw the expected product (others may be possible, but you are probably not aware of these additional possibilities to date).

1) Levofloxacin + HCl (include mechanism below) H H CH CH H C 3 H C 3 3 O N 3 O N

N N HCl N N

HO O HO O F F Cl O O O O mechanism: (abbreviated for simplicity)

H Cl Cl product

2) Levofloxacin + H2O in the presence of H2SO4 (include mechanism below) H H CH CH H C 3 H C 3 3 O N 3 O N

N N H2O N N H2SO4 HO O HO O F F OH O O O O mechanism: (abbreviated for simplicity)

H OH2 product

O H H OH2

3) Levofloxacin undergoing hydrogenation with a Pd catalyst present

H H CH CH H C 3 H C 3 3 O N 3 O N

N N H2 N N Pd HO O HO O F F O O O O

4) Levofloxacin + Br2 in the presence of CHBr3

H H CH CH H C 3 H C 3 3 O N 3 O N

N N Br2 Br N N

CHBr3 HO O HO O F F Br O O O O

M. (1 pt.) Is this molecule aromatic? Write YES or NO. Yes

N. (4 pts.) Would you predict that Levofloxacin exhibits better solubility in water or ? Briefly explain your response, including references to both the antibiotic and selected solvent.

Since both Levofloxacin and water are polar, the former is expected to be miscible in the latter solvent. Benzene is a nonpolar solvent.

O. (4 pts.) In 2011, the FDA added two Black Box warnings for this drug in reference to spontaneous tendon ruptures and the fact that it may cause worsening of myasthenia gravis symptoms. Such an adverse reaction is a potentially life- threatening event and may require ventilator support. Would you expect these warnings to be relevant to a racemic mixture of the drug? Briefly explain why or why not.

These warnings would NOT be relevant to a racemic mixture. Recall a racemic mixture is an equimolar mixture of two enantiomers that cancel out one another. The FDA warning is applicable to a specific enantiomer of Levofloxacin.

2. (15 pts. total; 3 pts. each) NOMENCLATURE! Use the appropriate IUPAC notation to name or draw each of the organic structures below:

10 A.

OH cis-5,6-dipropyl-5-decen-4-ol

1

B. 2 2-ethyl-6-methyl-1-propylcyclohexene

6 1

p-bromonitrobenzene C. Br NO2

D. trans-3,3-diethyl-6-methyl-4-nonene

E. 3-methylhexyne

3. APPLICATIONS! (20 pts. total)

A. (4 pts.) Assume that you have two unlabeled bottles, one with cyclohexane and one with cyclohexene. How would you tell them apart by carrying out the learned laboratory techniques in this section? What qualitative experimental results would you expect? To distinguish an from an alkene, one could perform the bromine test and/or the potassium permanganate test. For the bromine test, the alkene solution will change from red to colorless as the alkene reacts with bromine. With respect to the permanganate test, the alkene solution will change from purple to brown (as the alkene is converted to a glycol).

B. (4 pts.) Benzene is a liquid at room temperature, but (shown below) is a solid. Account for this difference in physical properties using chemical principles learned to date.

In view of the greater surface area (and larger molecular weight), naphthalene exhibits greater London dispersion forces, resulting in a solid. Naphthalene

C. (6 pts.) Describe how you could prepare the compound shown below from an alkene:

H2O

H2SO4 OH

3,4,4-trimethyl-2-pentene

D. (6 pts.) Consider the Fischer projection of D-ribose shown below, an important carbohydrate that will be studied in Sections Five and Six. Applying what you have learned in class, convert the Fischer Projection into its proper 3-D bond-line notation using the provided skeletal structure on the right. H O

H OH HO H HO H

H OH = HO H

H OH H OH O

CH2OH D-ribose 4. SHORT ANSWERS! (15 pts. total; 3 pts. each)

Briefly define and/or explain each of the terms listed below.

A. diastereomer - possess the same molecular formula, same connectivity, different spatial arrangement, but not mirror images.

B. Captopril - effective for the treatment of high blood pressure and congestive heart failure; it is manufactured and sold as the (S, S)-stereoisomer as shown. O

N SH

H3C H

COOH H

C. structural - having the same molecular formula but a different arrangement of atoms; these are unique compounds because of their structural differences, and they have different physical and chemical properties.

D. dextrorotatory - a pair of enantiomers rotates plane polarized light by equal amounts in opposite directions; a plus (+, dextrorotatory, clockwise rotation) sign is used with the name of a chiral compound to indicate the sign of its optical rotation.

E. achiral compound - molecule does not have 4 DIFFERENT on it; such a molecule is identical and does NOT exhibit enantiomerism.

BONUS! (9 pts. max; 3 pts. each)

There are numerous different molecules with the molecular formula C8H8, but there are only 17 constitutional of C8H8 in which EACH carbon atom is bonded to only ONE hydrogen atom. Draw (using bond-line notation) 3 different molecules with the formula C8H8 in which EACH carbon is bonded to ONE hydrogen atom, and every carbon atom has a full octet.

Possibilities may include: