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. k Vv. 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 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 129 nL. /28 ML__s/s Vi v6 VI. 2 Vil. /20 vill [a Ix, /22 total 1200 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:1. 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). Apis) Q 9 wh, & 4 better aucleophile thaw HO, a Nis, Hye because Mi less lech ewegative than 0, The reactuw wvilves rote detommiap 9 Addstun of the wucleaphile to tke AD HO. Carbony! 7p B. (6 pts) Hele vi favored 4 4. Nacn CHsGN Niylic, hoolides, cuith the 48 Nacn oe eee Find afin i cane he hot valerseiis Laban Stem differences me mininal; bth me primary. d raw a > bh be pe wtavembl stork yY 9 _Liaer Hed aan favial 5 a ects he 7 t >A ys all geebal Me Me 42- ani! pos 3 nee requires eclipsed cowferwor es oe pe Ho Bon Ho + NO =~ Bee wo Wit Ho” Kou x = oy" 7 toe “ . km HOW on m7 ae HO” en * HOW SoH C4 on be Me echas 5} higher CNY | his hor every TS. SeougerIL. (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. 0 22 no reaction by 8] c3H;e0 Ny AN) fe \_AsNs_, [x] AQNOg, H20 \s : H20 CrHy40 M] cutts0e 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 calculate the expected chemical shifts. Label each carbon with the chemical shift position from the |3C NMR spectrum (some assignments might be ambiguous; please indicate). Arco) — Ambiguous ome HAT 4.3, siuglet tl ome H at J 8s, Sinty $11 > LNT 4 Seay, salt # rN F as 7 ha ea eet 4) 27H2 #2, Cems Si) B. (2 pts). Indicate the two most important features of the IR spectrum for H in support of your structure. ed, stretch at «hho can"! M-0 bed at Ca 0 wun! coy sete at spe ce! aot bend ut ca 990 ca"! S30 C. (3 pts). Draw the best structure for M. Indicate the two most important feature of the IR spectrum in ‘support of your structure. Jaze stretch at w [7l0tn"! Ho ~on stretch tt ~ 3hye tou"!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. £ a, 0%, 3H K CXC suse, aysodd dvigtet J7 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. pelief of Dry waStke ame OL + hh oo duewie wy O awl, ny % Oo lw water: me) "} loably cone en ee 4a hho: Ce Of yr Cae uw Os Dn? OF a4 | a £ 4 A \4 pay CR wy Op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 $03. 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 Et3N. 4 Q Eun Sy RGEO + H:0 + SO, 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. aun . SN — + SO. + H,0 Hoon Lasy Sraathon of | As sed He ete heaiaeit abe Allows a secon" aeidthas toe wl e 6 a bebe 1 : o-te0 oN u wot BY py U r |IV (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. H IH ° — + Ht OH on 8 ¢ ‘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 Formaige of Bat pH 7. 61.» 208 iH hy @ al Cn ica sph —@ 7 on ow no B. (14 pts) In these modern times, a clever organic chemist ought to be able to analyze the reaction and create an antibody which would serve as, a catalyst selective for B. In a crude attempt, the molecule X was prepared = -R 7 as the key structural piece of an antigen to stimulate antibody formation. oH From the array of antibodies produced, one was isolated which selectively = sdecnainoprotsinto accelerated the formation of B. ‘favor antody generation 1, (7 pts) Analyze X as the choice for antigen. Include in your answer what the goal is in choosing an antigen to generate a catalyst, identify and discuss the rate-determining step for formation of B, describe the hypothetical ideal antigen, and analyze X as the choice for the antigen. In what aspect(s) does X satisfy the ideal? Itmight help to consider the an important resonance structure for X. tigen) should mimic the thonsiten stele tor the inte deler pati ¢) Tha An’ ‘pew 2 eee ae His wclades thm poiitien (rnd structure) An? partial charges ) For Be be-cleterna rinsing step ti the abdsbyis to the Ctrbory) Cte 4) Tha deal awtigen wil hike @ L-menerd vig ath 5H on ) m del dou, 56 ow aw adjaceah erterwal ae aad An -OW Fabebeet i 5+ [ee 2 Ths tesonance | | Py struckire shows a there re partial on of charges ww the Ayht place eH 6 Gned ning Stee ; Guet -on br binding ¢ recoquiton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. Lo zd by prritunins J fer angi transitun state will be stobil pe or Lew Acid wegr the c-, And by prrrbriniy A oO, or heje wear the $+. ; , athe ; Typeal base: higtidwe b ‘ Dypreal H® ; seine, tyrosine, frie } 6 Lytle 17 ta bosgc + prset as aly, ») fenchons ns ded V. (16 pts). Reaction of acetaldehyde in the presence of a small amount of acid gives a mixture of two isomers, D and F, CgH203. 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). TR: 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 15C, 'H NMR, and the IR spectra. Draw the structure for F and explain how it is consistent ith the !3C NMR spectral data. Cache doubly § 45] Ke geartet, 5 5.25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. rom bod “Si on Oened# ot oO oN ey (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 coresppgding bond in "mutant NADH"? Explain carefully. ° Go gi, sn le bond; : i Peat + he rior a me hl Sara, ‘ire a) 4 “Single © B. (5 pts). Leaving aside the role of the enzyme, how on you compare the intrinsic reactivity of the normal NAD with the mutant NAD in the oxidation Less reactive? Nochange? Explain your choice. The WhO 1: more elect ww “hot Conpited the nutut, Aho He prdud pina ji vbabilsed by the amilectyge Miouauce. This renkes the wetarn] leysins were Yeadkie toward add ited fy 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? Auary pitermdimos: H-bond megytonce b deo bool dideboa ba, daa, tas orn chiens with [yrictisngon a hydinphobic kerr cioa wrth the plaudr nay, Eons: dane @ Aspartate Mba ater hydrophobic bic: tyrosie Th -tyrtem og th 7A fam ’ ow Asoc = ¥ L)-on ebro << A ay 2 wn he Ty bond Aoniatins to the Sida Chany aid Cab bony ) ed would terthey awctease ae tres keticteagy 10 the ose WAS wih eatin D more PAT duc i bons diy, a Mipartete B ond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 surpmarize the mechanism fa, med bate tp Veriton bistidue to texwe &* from Oh. Use R-G--H terme H ayparnude fo Alt to basicly A histidux, 43 5 Behe |e homatrpsris als igo | Raed it rm veh 1 mininsite, | pe vzate™ Rk “0 y Fie aw cleckrophilic mits arowe erridiannsn sou destabies: 2 2 tol tog v I. 20 pts). A. (10 pts). The alkene N reacts with ethyl alcohol in the presence of a smal] 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. Gprers on _He8e excess EtOH | Pr Heo=c. (trace) . / MSOF a £ " - (trace) 5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. Oo (02 G g — + CHgOH Ho=c el HOS 0 Be or OTL a so. - ayer T @k 4 | on La ty le “8 chem, i => AF a CO Et > the X?7Yr2 C. (8 ps). Using conditions 3, compound Z reacts most rapidly compared to X and “e sie, ©, WA, Ach 4 dh He ‘CH Write the most reasonable mechanism for this process and explain why Z reacts faster than X and ¥ by this mechanism. Be sure to specify the other product(s) formed. whee Mf eee a Keid-catalyred E} J chim intron yk, 4 Ae J Pew ritlen * 10 Q Oy fs A 4 A es Ait? foured oy the 4 Te eC acdecutae pie Pewiratig 2 leads toa tettioy chin 7 , i rete, ¥ 2 prnny cat Z qins 4 ? lah mn, highe rate, ke thy) ae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. 99 Me Me a. BHs c. pTsCl d. PBL Me Ph H ph b.HzOao oe orecie Ho fo A. (6 pts). Write the mechanism for step, structure of T. ” +e <7 es Cet B. (2 pts). For structure T drawn in part A, how many stereoisomers are possible in general? one nwo six. eight (circle best answer) C. 2 pts). Considering t eegisoiiers of T formed in the reaction, how are they related? uantiomers> diastereoisomers. other (circle best answer) D. (6 pts). Choose one of ie stereoisomers of T which is actually formed in the reaction. Use the sawhorse or Newman, Projections in! draw this cee in the three most ule le conformations. Hata ache [nach et ved “ee 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- ay U 2 writing a detailed mechanism. 4 “ot 4 wpe aa ttn 2 £2 Ae Du On Ahi 4 e Se. trawsiton ti Favored. BR pl \ tags iSpectral Data Problemyj. Structure H CsHj90. No significant UV absorption ‘ot coc, 0-300 Pa 0 0 ‘i « 0 2 2 Weberreraee?Structure K C7H)4O_ No significant UV absorption 1H NMR 6 1.20 (s. 3H) overlapping with 8 1.1-1.3 (multiplet, 10H): 8 1.60 (broad s, 1H Structure L C7H)4O No significant UV absorption 1H NMR 8 0.90 (t, J=7Hz, 3H) overlapping with 6 1.1-1.3 (multiplet, 4H): 8 1.3-1.5 (multiplet, 6H); 5 1.6 (broad s, 1H) Structure M CyHg02_ UV Amax 256 nm (é 10) IH NMR 8 2.1 (s, 3H); 8 1.6 (broad s, 1H); 5 2.6 (t, 2H); 8 3.91 (t, 2H. § 5 5 3 300 1300109. 10009900 0a as ii sw WAVERNGM mt MCKONS