"Pip tazo" is a nickname given to a popular combination of antibiotics prescribed for a variety of infections. A.

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1 ame I. (6 points) Page 1 "Pip tazo" is a nickname given to a popular combination of antibiotics prescribed for a variety of infections. (a) ircle all the tetrahedral (chiral) stereocenters in both piperacillin and tazobactam and give the appropriate stereolabel. piperacillin (b) Identify any/all aromatic groups by using an arrow to point to the ring system; write the total number of delocalized electrons in the system next to the arrow. tazobactam 18 For each of the atoms indicated with an arrow, provide the atom's most reasonable hybridization as well as its electronic geometry (VEPR) and observable geometry (write none if it is not observable). hybridization electronic geometry observable geometry tazobactam 1 atom atom 1 atom atom. Be sure to include all information on connectivity and stereochemistry in your drawings and your naming. (c) Provide an accurate and complete three-dimensional (a) Provide the orbital picture for this organic product (considering all valid structure of the resonance contributors when you assess hybridization for Br starting a Br each atom). You should use lines, dashes, wedges, and p material orbitals (lone or overlapping) to show the direction of all abr electrons (or empty orbitals) in your drawing; you may just write - for the methyl group. All bond angles should reflect the appropriate geometry and hybridization chosen Br for your drawing. (b) Provide the complete name for the organic product shown, with stereochemical labels if needed. 6 10

2 II. ( points) In January of 016, Meldonium, an off-market antiischemia drug, was added to the list of pharmaceuticals banned for athletes. It recently made the news when Maria harapova (WTA) admitted that she has been using the drug for ten years. (a) Draw a ewman projection of the 1 - bond in a conformation in which some intramolecular interaction occurs; view with the 1 in front, and Indicate at least one specific interaction that could inhibit bond rotation by circling the specific atoms involved. ame Page 1 meldonium (b) Ischemia is the reduction of blood flow in certain areas of the body, often noticed by a bluish tinge to tissue. Given that the only acidic proton in meldonium has a pka of, draw the form(s) of meldonium that would predominate in the bloodstream at p 7.. (c) From the set of bases given in the box below, circle those bases that can deprotonate the most acidic proton meldonium favorably (Keq > 10 ). a K 6 a 5 Electrophilic aromatic substitution reactions are very important in the synthesis of many pharmaceuticals, including the very famous ibuprofen. Follow the first reaction in the synthesis of this common over-the-counter drug. You may use B + and :B as needed. Al (a) how the formation of the electrophilic partner; be sure to show the best possible structure and all products. Al Electrophilic partner and all other products 10 (b) how the complete EA reaction, using the electrophile you generated in part B(a). Draw the electrophilic partner here 9

3 III. ( points) ame Each of the following transformations demonstrates some form of selectivity yielding a single major organic product. Provide the other information requested. Page (a) (i) Draw the product (ii) Draw a ewman projection showing the conformational alignment favored for the formation of the product. The with the leaving group should be in front. Br (b) (i) Draw the starting material 5 (ii) Draw the product Molecule 1 (c) (iii) Draw the complete chair conformation for Molecule 1 that shows the conformational alignment favored for the formation of the elimination product. Be sure to show axial and equatorial positions for all substituted ring atoms. Then provide the curved arrow mechanism for this reaction. (ii) Draw the product a (iii) how the chair conformation of Molecule 1 favored to undergo an E reaction and provide the mechanism (ii) Draw the product 7 Br Fe For each of the following connectivity drawings check all the descriptions that apply. (a) (b) (c) This connectivity represents 1 unique molecule a diastereomeric pair an enantiomeric pair or more stereoisomeric molecules only chiral molecules only achiral molecules This connectivity represents 1 unique molecule a diastereomeric pair an enantiomeric pair or more stereoisomeric molecules only chiral molecules This connectivity represents 1 unique molecule a diastereomeric pair an enantiomeric pair or more stereoisomeric molecules only chiral molecules only achiral molecules only achiral molecules

4 IV. (0 points) ame Page In each of the following reactions more than one product is formed. Draw each product in its appropriate box (considering optical activity; each reaction yields at least one product of each category) and provide the MR information requested about the starting material. Be sure to show all structural and stereochemical properties unambiguously. The MR spectra for A 1 MR signals 1 MR signals A (cat.) The MR spectra for B 1 MR signals KMn 1 MR signals B. The MR spectra for Balance your reaction 1 MR signals a 1 MR signals D. The MR spectra for D 1 MR signals (excess) Pd/ 1 MR signals D E. The MR spectra for E 1 MR signals 1 MR signals E

5 V. (7 points) When 1 is heated in aqueous acid, a significant amount of is produced. This product can be explained mechanistically in just three steps: protonation of the oxygen atom leads to a resonancestabilized carbocation that then shifts, leading to the final product. ame Page 5 (cat.) heat 1 (a) In the first step of this transformation the oxygen atom in 1 is protonated, yielding an intermediate that is best drawn as a set of resonance contributors; one of these (the best, and the only with all closed shell atoms) is given to you. hoose the acid you expect to be present under these conditions, provide the mechanism, and draw the complete set of resonance contributors which reveal the delocalization of the carbocation in the ring. 1 draw the acid and the mechanism for protonation all-closed shell resonance contributor resonance contributors showing delocalization of the + in the ring 9 (b) ow, using the best, all-closed shell contributor from the first reaction, continue to draw the complete curved arrow mechanism for the production of the final product, choosing hte appropriate acid/base as needed. ote that only one carbocation shift is observed. 9 (c) onsider the rings and give two reasons why the formation of this final product,, might be so favorable. Energy, G onsider the energy diagram below, which might be used to illustrate the reaction above. 1 b c d e f reaction coordinate (a) Using positional labels, state how you would calculate the following (give your answer as a mathematical equation) (i) the E a (ΔG ts ) of the rate determining step for the forward transformation? (ii) the E a (ΔG ts ) of the third step for the formation of 1 from (reverse)? (iii) the ΔG for the second step in the reverse transformation? (b) In this diagram, what positional label represent(s) the closed shell intermediate provided in part A above? (c) In this diagram, using positional labels, what represents the rearrangement step from part A?

6 VI. (0 points) ame Page 6 Describe the relationship between the starting materials and provide the missing for each of the following reaction pairs. If any product forms as a stereoisomeric mixture, then draw only one, clearly showing valid stereochemistry, and write "+ enantiomer" or "+ diastereomer" or "+ stereoisomers" (when more than two stereoisomeric molecules can be drawn). (a) Product(s) (cat.) 1) B ) /a structural isomers stereoisomers (b) Product(s) (a) Product(s) (b) Product(s) Br structural isomers stereoisomers. (a) Product(s) (b) Product(s) a Pd/a Pb structural isomers stereoismers D. nly ionic compounds form in each of the following reactions (a) Ionic product (b) Ionic product Br 1 equivalent structural isomers stereoisomers