Chemistry 303 fall 1996 FINAL EXAMINATION 1:30 pm, January 15th, 1997 Duration: 3 hr There will be an additional 30 min allotted for the course evaluation before the exams are collected Name, Lab TA. 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 and description of spectral information. READ each question completely and carefully before answering. The last two pages are spectral data for Question 2; you may detach them. Grade: I: p29 Tit /28) M__/18 IV, /21 ve Vi. s22 ee) VIL_/24 Ix, 122 total /200 ‘There are 14 pages in this exam; please check now to be sure you have a complete set. EVALUATION FORMS ARE AVAILABLE IN THE FRONT OF THE ROOM. IF YOU HAVE. NOT DONE SO ALREADY, PLEASE FILL ONE OUT BEFORE YOU LEAVE AND LEAVE IT HERE. Pledge:I (29 pts) For each of the following pairs of reactions, predict which will occur faster. Write the organic product(s) for the faster reaction and give the single most important reason for the difference (explain in detail) A. (pts) Q ca —NHs AD 140 : CHyCN Yee Nacn CAs \AAp, + neon SHs0N B. (pts) D. (7 pts) yi CHgMgBr 0 S ~ CHgMgBr Epis) Ha f nae HoH Ho wun * HOW WOH 4 Ho NOH ° Ht H ae HOLOH 0 wy + HO" Kon How Nt 8II. (28 pts). The molecule G undergoes substitution very rapidly to give H, simply by heating in water. The related compound, J, is inert under the same conditions. Substitution can be induced with J, using Ag*, to give products K and L (isomers). With Ag*, G again gives H. As part of the structure proof for H, it was treated with ozone (followed by dimethyl sulfide) to give M. The spectra for H, K, L, and M are given at the end of the exam. OH, foe mrmeion te. tea, 5, heat HY} CsH100 J be BN Nn aie Poste (Ne #40 oe C7Hy40 MJ CaHy02 A. (9 pts). Draw the best structure for H and correlate the NMR spectra, Draw in all the hydrogens, and identify groups of equivalent Hs by labeling with the approx. chemical shift value and pattern from the !H NMR spectrum (p 13). You need not caiculate the expected chemical shifts. Draw the structure again showing no hydrogens, and label each carbon with the chemical shift position from the !3C NMR spectrum (some assignments might be ambiguous; please indicate). B. (2pts). Indicate the two most important features of the IR spectrum for H in support of your structure. C. (3 pts), Draw the best structure for M. Indicate the two most important feature of the IR spectrum in support of your structure.D. (5 pts). Write the structures for K and L which best fit the spectral data and reaction mechanism. Give ‘one important feature from the !H NMR spectra of each which is confirmatory of the structure. E. (9 pts). Write the best mechanisms to rationalize formation of H, and also of K and L, and explain the high reactivity of G compared to J when simply heated in water. If you do not know some of the structures, just write what you think might happen in these reactions. HO, heat G Br or AgNOs, HzO On AgNOs Br H20IIL. (18 pts) The oxidation of primary alcohols to aldehydes can be accomplished by numerous reagents. |A, (9 pts) One reagent which is useful in producing aldehydes is SO3. Addition of a weak base such as triethylamine accelerates the process. Write a mechanism to show this conversion with the generic alcohol, R-CHz-OH — R-CHO. Be sure your mechanism accounts for the products shown and the role of EtsN. t 9 etn R-G-Q +8, ——e R-C=O + H,0 + S02 HoH OO 4 B. (9 pts). The di-alcohol, 1,4-dihydroxybutane, behaves strangely under comparable oxidation conditions, giving the cyclic ester (lactone), A, instead of the expected dialdehyde. Please rationalize by writing the best mechanism for this process. a Os Ho” Lon Gor 70 + S02 + 1:0 aTV (21 pts). When two pathways are readily accessible, it is often desirable to design a catalyst which accelerates one of the pathways selectively. Consider the following reaction, which gives a mixture of B and C. ° IH IH H ° H ‘OH OH on ® c A. (7 pts). The formation of both B and C occurs slowly at pH 7, and without much selectivity. Write a ‘mechanism to show the formation of B at pH 7. ° B. (14 pts) In these modern times, a clever organic chemist ought to be yt able to analyze the reaction and create an antibody which would serve as a catalyst selective for B. Ina crude attempt, the molecule X was prepared i as the key structural piece of an antigen to stimulate antibody formation. oH From the array of antibodies produced, one was isolated which selectively = side cnain to poten to ‘antibody generation accelerated the formation of B. 1. (7 pts) Analyze X as the choice for antigen. Include in your answer (a) what the goal is in designing an antigen to generate a catalyst, (b) identify and discuss the rate-determining step for formation of B, (c) describe the hypothetical ideal antigen, and (d) analyze X as the choice for the antigen; (n what aspect(s) does X satisfy the ideal?), It might help to consider the an important resonance structure for X.2. (7 pts). The antibody catalyst has an “active site” which provides binding and also chemical interactions to accelerate the process. Which of the common amino acids might be located in the active site in order to provide the chemical interactions which speed the formation of B? Choose the two most important candidates and explain your choice in words and pictures. 'V. (16 pts). Reaction of acetaldehyde in the presence of a small amount of acid gives a mixture of two isomers, D and F, CgH}203. In the !3C NMR spectra (proton decoupled), isomer D shows two peaks, while isomer F shows four peaks. The IR spectra for D and F are nearly identical. For D: !H NMR 6 1.51 ppm (4, J=7Hz, 3H); 5.75 ppm (q, J=7Hz, 1H). IR: 2900 (m, several peaks) [no other peaks between 4000-1500 cm-!} A. (9 pts). Write a structure for isomer D which is consistent with the spectral data, and explain how it correlates with the !3C, 1H NMR, and the IR spectra. Draw the structure for F and explain how it is consistent with the 13C NMR spectral data. so H acetaldehyde B. (7 pts). Write a mechanism for the formation of D from acetaldehyde and a catalytic amount of HCl.VI. (22 pts). NAD is an acronym for Nature's oxidizing agent; it is a complicated molecule with a pyridinium ion as the reactive center. If one mixes ethyl alcohol with NAD at normal temperatures, the oxidation reaction is slow. However, in the presence of an enzyme, alcohol dehydrogenase, the mixture of NAD and ethyl alcohol rapidly produces acetaldehyde and NADH. A mutant cofactor, where the amide side chain is replaced by an isopropyl group, is much less effective, using the same enzyme. ° 9 HaC-CHp NH On NH He CY tod | OS ON R a oy y NAD NADH A 2 (business end only) mutant NAD/NADH A. (5 pts). Consider the single bond indicated with the arrow in NADH. How would the barrier to rotation of this bond compare with the corresponding bond in "mutant NADH"? Explain carefully. B. (5 pts). Leaving aside the role of the enzyme, how would you compare the intrinsic reactivity of the normal NAD with the mutant NAD in the oxidation process. More reactive? Less reactive? Nochange? Explain your choice. C. (6 pts). One role of the enzyme is to bind to the NAD. Imagine two (your choice) of the common amino acids being present at the active site of the enzyme, and discuss how they might provide the binding interaction with the portion of NAD shown above as the "business end". Would this interaction alter the intrinsic reactivity of the NAD in the oxidation process?D. (6 pts). ‘The enzyme also provides chemical catalysis. Again choose two of the common amino acids which might be present at the acitve site of the enzyme and discuss how they could provide acceleration of the oxidation. These amino acids can be different from those in part C. You may want to summarize the mechanism Tl @0 pts). A. (10 pts). The alkene N reacts with ethyl alcohol in the presence of a small amount of sulfuric acid to give P; if the reaction continues with excess ethyl alcohol a new product appears, Q. Write a mechanism to explain these observations. You need not show every proton transfer, but be sure you make clear the role of the sulfuric acid as a catalyst, Pots Non HS HpSOq “excess EIOH > Ho=c. “Wece) J” ¥eS0, N (trace). B. (10 pts). Write a mechanism to account for the somewhat different result, when N is allowed to react with water containing sulfuric acid, leading to the ketone R. 9° —CHy HyS04 y / ae + HOH H2c=C, H,0 ss n\_ ® R VIII. (24 pts). READ THE ENTIRE PROBLEM FIRST. There are at least four distinct mechanisms for ester hydrolysis, depending on the conditions and the structure of the substrates. The products are different for each mechanism. For a given mechanism, the rate is strongly dependent on the substrate structure. ‘Three substrates are: Eour typical conditions are: ° 1. NaOH, HO or CHjOH solvent : 9 Hog J GH Hs He 2. CHy® CH,OH solvent fF ee Hy CH 3. HjSO, (catalytic amt), ether solvent | "3 ote Tyo Hc’ 2 ° CH, 4. 1380, (catalytic amt), H,0 solvent | 8° x : A. (8 pts). Using conditions 1, compound ¥ reacts most rapidly compared to X and Z. Write the most reasonable mechanism for this process and explain why ¥ reacts faster than X and Z by this mechanism.B. (8 pts). Using conditions 2, compound X reacts most rapidly compared to Y and Z. fe} 9 es He Hs Hat Hat 2 Heat Write the most reasonable mechanism for this process and explain why X reacts faster than ¥ and Z by this mechanism. SS * HyC7" ScHs C. (8 pts). Using conditions 3, compound Z reacts most rapidly compared to X and Y. H: 4 CH; 9 : 6 Ha Hs ACH oe + a Hee” 2 “oly Hse Write the most reasonable mechanism for this process and explain why Z reacts faster than X and Y by this ‘mechanism.IX. (22 pts). Consider the following sequence, which results in the inversion of the geometry of the double bond. T (and U) is formed as a mixture of TWO stereoisomers. Me Me a. BHs epTsCh 4 sok “s ae Ph. b. HzOz/HO eg lee Ho “Me a peer ete ° A. (6 pts). Write the mechanism for step (a). Ignoring stereoisomer possibilities, draw the overall structure of T. B, (2 pts). For structure T drawn in part A, how many stereoisomers are possible in general? one myo four six eight (circle best answer) C. (2 pts). Considering the two stereoisomers of T formed in the reaction, how are they related? enantiomers diastereoisomers other (circle best answer) D. (6 pts). Choose one of the stereoisomers of T which is actually formed in the reaction. Use the sawhorse or Newman projections, and draw this stereoisomer in the three most stable conformations. E. (6 pts). Your choice of stereoisomer in part D is then converted to U and finally to the Z-alkene. Explain the selective formation of the Z-alkene from U by writing a detailed mechanism.Spectral Data *robl itructure H_CsHio0. No significant UV absorption ‘o3 cocig 0E-200 we A eee eee |Structure K C7H)4O No significant UV absorption 1H NMR 4 1.20 (s, 3H) overlapping with 8 1.1-1.3 (multiplet, 10H): 5 1.60 (broad s, 1H : k : Structure L_C7H140_No significant UV absorption 1H NMR 6 0.90 (1, J=7Hz, 3H) overlapping with 8 1.1-1.3 (multiplet, 4H): § 1.3-1.5 (multiplet, 6H); 8 1.6 (broad s, 1H) itructure M_CyHg02_ UV Amax 256 nm (€ 10) THNMR 82.1 (s, 3H); 5 1.6 (broad s, 1H); 6 2.6 (t, 2H); 8 3.91 (2H). var S68 eas WAVERNGM wt huCRONS