Chemistry 303 fall 1994 FINAL EXAMINATION 7:30 pm, January 12th, 1995 Duration: 3 hr ‘There will be an additional 30 min allotted for the course evaluation before the exams are collected Name Key = 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. Grade: 1, 0 2, B3 3. 28 4 9 5. 140 6. po 7___ 0 total: ___ 200 HW ‘There are HY 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. PLEASE FILL THEM OUT BEFORE YOU LEAVE AND LEAVE THEM HERE. Pledge:1 (20 pts) A. @ pts) Consider the NMR spectrum for compound (A), CsH11Cl: Draw the structure which best fits the spectrum. Explain how your structure fits the spectrum by discussing the relative areas, chemical shift assignments (calculate from the Table) and spin-spin coupling (or lack thereof). sua lest # aH ats? ¥s a vivale ! e 4 . CH EME ‘ “t stl ca, Sie (<2) a pm (5) B. (8 pts) Structure B is an isomer of A. Fill in the table below to show what the NMR spectrum would look like for this compound? There are four sets of equivalent protons; each as a multiplet. - ‘assignment, specity Telative area] approx, chem- | spliting relative to structure for this set_| ical shift, pattern a é 2 a b Lo Fi Ladet CF) EE Gz) z do Zz [LF 7p -| fad C. (6 pts) Consider the NMR spectrum for compound (C), C4HgBra: Draw the structure which best fits the spectrum. Explain how your structure fits the spectrum by discussing the relative areas, chemical shift assignments (calculate from he Table) and spin-spin coupling (or lack thereof). br rerIL. (33 pts) (A) (5 pts) Amines are better nucleophiles than alcohols (or water). Why? The wen bewtbrog electro pair pre held fess tiyhty with M, comport too w Roy, Ho, Bliler efecto! donor Ne pee @ less ele front. tha 2. (B) (6 pts) The reaction of a primary aminé with methyl chloride in water is pretty slow (reaction (a)), as monitored by measuring the rate of disappearance of the CH3Cl. Write a mechanism for this reaction, showing carefully the electron flow, aa + a. RCHNH, KCl ar CH;NH,CH)R (slow) a (© (pts) Having heard somewhere that nucleophilic substitution reactions can be catalyzed by acid, an Orgo student (not at Princeton, of course), tried to speed the reaction shown in (a) by adding excess sulfuric acid (as in (b)). He was shocked and surprised to find that he got only methyl alcohol under conditions (b) AND the reaction rate was even slower than in (a). Explain carefully how the addition of acid led to the different product and slower reaction. b. RCH,NH, + CH,CI = CH,OH (slower) SO, ity get,All, & Te arane pucleepoile -s reeaved wb B Veby r ti hile baoratle egeiti brian cols aed tb qin ny as Atudoniian sonr — Crly remaining wucoparle a wo 7 (D) (6 pts) He then tried the other extreme, adding excess NaOH to make the solution basic. The reaction was now much faster, but he found the same problem: CH3OH was the main substitution product. Explain how the addition of base gave the observed product and a faster reaction compared to (B). c. RCH,NH, + CH,cl —#__, cH,oH (faster) a9 ii NaOH Gu en jolt wucleaphit Lafi j 4 . entaverdble euilipnitn, An # proot wi puch = 7 Aber creortinbon cupared b LAME. Qe Ketebu! horinntl 4 H., ) (S pts) Give a specific le of an Sy2 reaction which is (higher rat i Show 2 ) {5 ps) Civea speci ample oar Sid reacon ich is accelerated (higher rate) by acid. i Typical Lor Alcohols or Amines: a + HOS CR n —> Rat ho @ () (S pts) As noted in part (C) above, the substitution of. methyl chloride was not accelerated by ‘the addition of sulfuric acid. This is a general observation for methyl chloride in Sy2 reactions. Why are ‘substitution reactions of methyl chloride not accelerated by the presence of acid? Very leu Einily of Mec: Gr it 7 . 2 pot very favorable; year SO he HU gin ony : owerkab Acted, does wit Loran (required for life!!) that carbon does not invert configuration 4. (29 pts) Ibis an important fact of life ‘temperature: (racemize) rapidly at room. x How Sha cmc, wh slow ng Pay = a ee HB A. (4pts) What is the configuration of A in the R,S nomenclature? ‘hat is the relationship between A and B? Circle best answer. enantiomel diastereoisomers meso identical B. (8 pts) Certain compounds, however, such as C, do undergo inversion just on standing in water at 25 °C. Explain the mechanism for this inversion. Your answer should accommodate the additional fact that base accelerates the rate of inversion. Your explanation should reveal the role of the carbonyl group and the -CN group in this process. i #0 NC, The proton «8 Hae PW ce, Be PN Heldic toy Conjigatioi) eo HD wweilable to 7 iate. nse; HANAT MG emedne. — AP 2 aw retin to We Cty wea other tue of Mey, gives fei Mixture ad of cra& (33 pts) (A) (5 pts) Amines are better nucleophiles than alcohols (or water). Why? . 4 far lous i) Sate Tour oh perade table, (Wve), stceaphiaity # dives Wh EM, Howrbensbiig © OWN fete tislih hell Conpared to! 0; pare readily donated (B) (6 pts) The reaction of a primary amine with methyl chloride in water is pretty slow (reaction (@)), a8 monitored by measuring the rate of disappearance of the CH3Cl. Write a mechanism for this reaction, showing carefully the electron flow. a. RCHNH, > gol WE CHNHCHZR Glow) a ft. 1\ 434 RCH wa, 7 w (© (pts) Having heard somewhere that nucleophilic substitution reactions can be catalyzed by acid, an Orgo student (not at Princeton, of course), tried to speed the reaction shown in (a) by adding excess sulfuric acid (as in (b)). He was shocked and surprised to find that he got only methyi alcohol under conditions (b) AND the reaction rate was even slower than in (a). Explain carefully how the addition of ‘cid led to the different product and slower reaction. >. ROHNE, + CHC 8B __ cao (slower) Ai 250, . s Te acid cquverts the Aune to ny AMMontite joi), which 1s won-snicleophs é Waker & He only srecleaghhe pecies Ett, athough @ & cy, Hh, event Anu theredore Peete HOC “® (D) (6 pts) He then tried the other extreme, adding excess NaOH to make the solution basic. The reaction was now much faster, but he found the same problem: CH3OH was the main substitution product. Explain how the addition of base gave the observed product and a faster reaction compared to (B). c. RCHNH, + CHCl aS CH;0H (faster) Nios te. By 1 the est auckophile, Ao reac thaw RUM, faster, a Hx a Se 4 continued6 - 2. C. (7pts) The simple amines such as E do undergo inversion rapidly at 25°C. Draw the transition state for this isomerization. Specifv the hybridization of the nitrogen atom inE and in the transition state. fx cH == HAL ht | : x a cscs D. (10 pts) An exception to the general rule for amines are the aziridines, an example of which is G. The barrier to inversion for G is much higher compared to E. Explain this observation using reaction coordinate diagrams which nicely represents the energies of the reactants, transition states, and products for the two processes (E —+ F compared to G +> A). You might use words also. Indicate AG#for each reaction clearly on the diagrams. i ae LA exes Sous H ESF hae same weny. : Sth have Sage, erry SN. HIN, af , a 3 ~ 1 3 a a ¢ AG < Sy G6 higher ewery thu Z daa to bond engle ebrmil, And that A frewue 1 every [tiger wi the tonsitin stakes heh Kepente Mw e cuideuny of pe Gord ah te (20° Br best everlypARES AIIGIE IDES EIS URIS EARN OE FEARS QUESTION BEFORE ANSWERING 7 5. (40 pts) Enzymes are wonderful catalysts, typically associating with a substrate and then using acidic and basic functional groups in the enzyme structure to promote conventional organic reactions by conventional mechanisms. One of the key reactions involved in glucose metabolism is the E2 elimination of water from cic aid (Fischer projection A) to form acoitc acid. By isotope labeling, it has been shown that the H which is lost is the one indicated by the asterisk in the structure of citric acid, below. COM |e , one of these HH Aconitase is aconitic HO-—CH,COH = — acid CO ¢ A A. (4 pts) Ifyou were an enzyme, and wanted to associate strongly with citric acid (A), what functional groups would you choose to use? Suggest TWO different common functional groups which could provide association with A and explain with words and pictures how the association works. You need not try to represent the enzyme. : oo . e Strongest Mseclation + Jone wterncbeil 8 Shek pe 4a AM, + i feaeou aha y .> xe Mom day hae Hy He a a uge Ge wh 40 -off an {2 43K EE wr —> aa ——_ can C. G pts) Which common functional group might an enzyme use to provide ACID catalysis? Specify one possibility and explain why it is more acidic than, for example, water. — oe or A O