ORGANIC CHEMISTRY 2 (CHOC?) no. 2 DATE: Monday, November 13", 2017 | PLACE: A, Jacobshal ‘TIME: 18.30-21.30h TEACHERS: Prof. G. Roelfes / Prof. W.R. Browne NAME + INITIALS: A af Voocler, STUDENTNUMBER: A MASWeYsS STARTING YEAR: STUDY: Chemistry / Chemical Engineering / Minor / pre-Master + This exam consists of 5 questions (85 points) that each consist of several sub-questions. There are 16 Pages; the lst page is a blank page. Check whether your exam is complete. * Read every question carefully before you start writing down the answer. * Cheek your chemical structures! Mistakes will lead to deduction of points! * Write the answer clearly and legible inthe white space directly under the question. Ifnecessaty, use the ‘blank page at the end. Clearly refer to this! * Tf you are not sure about your answer, firs try it on scrap paper. Extra scrap paper can be obtained from the invigilator, * The final mark ofthis course will be calculated by adding the points eamed in this exam (max. 85) to the points eamed with the assignments (max 15) and then dividing by 10 and rounding off to the nearest half mark. A 5.5 cannot be given; to pass you need >SS points, ‘vila i Table of Pauling Electronegativty Values La MA IA _IVA_VA_VIA vi 7a Bs BT 2) Li] Be B/C/N/O|F [Ne 10 [15 20| 25] 30] 35 | a Al 8 IVB_VB vip VIB_—vi— 15 _u| ts PEs pee Pr pee past ‘TV /Cr|Mn} Re | Co] Ni [Cu 13 [45 [us | vs fis’ as [a] ns | o eS ee Ru} Rn] Pal Ag 22/22|22[4 6 Os| Ir | Pe] Au | eye Te pr 7 Bh} His| Me | FS Ot eae | Lanthanides | Ce [Pr |Nd /Pm|Sm| Bu [Ga Tb |Dy |Ho [Er frm or sar sper 100" Actnides Th] Pa! U | Np] PulAm|Cm| Bk| Cr] i |ism| Mal |Question 1. Reactions (28 points; 2 points per question) Draw the chemical structure of the (main) product of the 10 reactions given below (no mechanisms!): @ 20 1) LiAIHy Ne COS, amotenene wan LI © <> ° i : O cat H", A ~~ o~ 1 ant Cos © @ o 1) CHsCHaMgBr Ne 2) Ho Yo es© @ @ pg 4 & 3 2 wh Noo HOH CHOH aa OH on™ acetone, cat H” ——<——{ can ot ei TS ez 1) NaNOz, HCI NH. a [> Cpe CF AD 0c VL Sw) 2) co” Nv ° CR + CH;OH ‘0 e oO ee pon q SOCth@ Br NaN, NHs() Mlk 4, high pressure k, Lith inners my « 7 Y- Give the chemical structure of the missing starting material / substrate / reagents (indicated by “X”) in the following 4 transformations (no mechanisms!): w&) NHy x Cr CWT KvCly a> Ay, Iho o 4) LiAIH, NO x A Oo 2) H,O (workup) pale gon 6 oe ( cre ow ¢ t 4 ‘ hye (m) x 9 CO Cos Br / Maou @) ’ Xx (CHg)2CuLi AA, 0 7S Nosy | | | |Question 2 Theory (18 points; 9 points for a, 5 points for b, 4 points for ¢) (a) Reaction coordinate diagrams are used to describe how the energy of a molecule (or pait of molecules) changes during a single elementary step in a reaction. ch A B. v c. wT b 2 ? 5 : ;: ; i 5 i é é @ e Co ’ Reaction coordinate Tent emclials win canes = Cxo eric exolwme aber: In the reaction coordinate diagrams shown above (A, B, C) label the minima as R (reactant), I (intermediate) or P (product)? ii) Identify the rate determining step and transition state energy in each case. In each case state whether the reaction is endothermic, exothermic, endergonic, or iti) exorgonic (choose one term in each case).Consider the reaction shown below, which has an overall driving force (AG) at a particular temperature of -200 kJ mol, The mechanism of the reaction needs to be investigated but before any experimental work can be done we have to propose a mechanism. Overall reaction on + Br —- 40 + iv) Propose a reasonable mechanism for this reaction. Br ech vy) | pl Gr consent Draw an appropriate reaction coordinate diagram that describes the multistep mechanism that you proposed in question (iv). In your drawing indicate clearly a, Reactants, intermediates and products (show all molecules/ions involved at each point clearly) O° b. The most appropriate label on the y-axis o « c. An appropriate normal (vibrational) mode or bond angle that defines the | reaction coordinate best (there are several possible but indicate only one) 0 d. Show clearly in your diagram whether the reaction is exergonic or endergonic or e. Label AG? and AG! (activation energy) for the forward reaction(s)_ 0» Vu nee be be 6 De ped oa (iv) oui Dak shenlfb< Comm Crrwbe cberserk Sener(b) Consider the following form of the Eyring-Polanyi equation and the Arthenius equation: t= Aeo(-f) ‘The term ‘k =" appears in each equation, representing the rate constant. Explain briefly what is the fundamental difference between the rate constant in each case. \e" (paves ser M7 > sinste panels nd seme ct Os Gyoy ae aie © be peeks k > Mer seer ° D L ais ones ii ‘What is meant by term E,? In your answer consider the distribution of energies across the molecules in a reaction.iii, The following plot (known as an Eyring plot) was obtained for a reaction: A+B>C+D in which the ratio of produets (C and D) vary depending on temperature. In fact at low temperature (200 K) only C is obtained, while at high temperature mainly D is obtained. The rate of loss of A was used to measure the overall reaction rate. Explain, considering entropy and enthalpy of activation, why the Eyring plot is not a single straight line in this case. Wha ate MA © wee Shasaudll * s ie KAD? © peeayacte 1n(Qe) | —h. Ark 20 ae ay terelen ahoy gs salen “Nl & ar _— : es a lente i &@ >A Qe Ae Ze oN er # ig eb AK en Pare oe angele oO ot oar & heer(©) If you compare the two compounds below, which of the two is the stronger acid? Give a reaction scheme of the acid/base reaction and provide an explanation for the difference in acidity. CLO ciel Luc veudion: —~ 0 a! cn Chet, 1S) =Parge Hog eypilibving awwos > ys o Question 3 Reaction mechanisms (20 points; 5 points per question) a) The retro-aldol reaction given below is a popular reaction to compare the activity of aldolase enzymes, because 6-methoxy-2-naphtaldehyde is fluorescent and, hence, its formation is readily monitored. Write a detailed mechanism of this reaction. Tat : , NaOH, H20 a : cor A HCO" HCO (b) Predict the product for the following reaction and write the detailed mechanism of this reaction. ge ° 6.5 re Aor @9 J? oaths c = A‘ ?(©) Consider the reaction below. Explain the formation of the product by writing the detailed mechanism of this reaction: ON A NO, 6 e ou (+ vroonsbe hreckuces | OYQuestion 4. Named reactions and general terminology (4 points; 1 point per question) (@) Give an example of « Hofinann elimination th Cj WSU coins ates co 1 ty =a Agre lav ae ‘s (b) Write an example of a Michael addition. CG t a aol, | he 6 pos le FF s ue e aalligs (©) What is an a,f-unsaturated ketone (draw a chemical structure to illustrate your answer)? (@) What is an iminium ion (draw the chemical structure to illustrate your answer)? Ou hts, 12sats apk Question 5, Synthesis and Synthesis Strategy (15 points; 5 points per question) (2) Suppose you are interested in making 2-(-(dimethylamino)propyl)phenol from indanone, How would you do this? Design a multistep synthesis of 2-(3-(dimethylamino)propyl)phenol from indanone. Give reaction steps and reagents (draw reaction schemes for the individual reaction steps, no mechanisms'). Also provide an explanation and motivation for the strategy that you have employed. rn — od 2-(3-(dimethylamino)propy!)phenol indanone ) nk amidalty >) CAV alee Sous of : or Oxy’ Oe > ty ! => Wh 4 co “he s-wserbenl ving bas Leen peel coal Pane is om elial om He acumalit vig vay TH seugrs o Breuer Vllegr Oxi ava ve “tha ceaulls inner becans Vol coe le epernedl bey cenmicbednn cone Ake ab sepued| amide is vedecadl _ ~ ~ Soy Hose: o E pn mPOA ace ae wen <20 . ole _ 1 CAY Pe CL OO > DO Se OC" g(b) Ina variation of a part of the total synthesis of the natural product Fukinone, product A ‘was prepared starting from compound 1 (see below). How would you do this? Design a multistep synthesis of product A from compound 1. Give reaction steps and reagents (draw reaction schemes for the individual reaction steps, no mechanisms!), Also provide an explanation and motivation for the strategy that you have employed. dcr == Lb prodiue’ ® compound 1 Key, chiewnag! nuh bal qoup ot rola J) Crapuate eedilig | VE patie on OB -emsecaccl Kelhas hea be eevee WK vedluudty | Kelme conten be tedlcee ahr, afl baduolysr, lo gill ws ches sok Lace 4 atledlal Gad baplealas DPM oxide 2 Sector, velo: 6 7 . x adsl culedd' © WMGL ) « 6 head Be lA ok Huh Koy Be ot Ean ‘ FAX RP ARTE CI al _ pas vil ete Wor Len Pee NY “St a> yp = fy Se? Roe(© Compound 2 is a related compound that was used for the synthesis of a derivative, Compound 2, can be prepared from compound B (see below). How would you do this? Design a multistep synthesis of compound 2 from compound B. Give reaction steps and reagents (draw reaction schemes for the individual reaction steps, no mechanisms!). Also provide an explanation and motivation for the strategy that you have employed. . corr = . lon ‘compound 2 compound B a nto b- cathe ving is creed \ enamine) mur / Ip! Covliaviomy K jP ~urmseduvallal lela a) Robwsm. > Robmsou | Lelin Hed muthel qrouy b cla ) aoe ay arylals to le vitodweed baat! ovtullatedin, Lar bas fe ledane vin veh . fine? % , Me => ol ot soptless 08 SQW ow 7H ol Co se 2 —_= LO é DMT g Nao Nae « a lho® cuoli ci paid re a dod