Organic Tutorials 3 rd Year Xmas Vac

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1 rganic Tutorials 3 rd Year Xmas Vac Third Year Reactive Intermediates: Radicals, Arynes, Carbenes etc. Radicals References: Moody and Whitham Reactive Intermediates, xford Chemistry Primer 8; Carey and Sundberg Advanced rganic Chemistry Part A, Chapter 12 and Part B, Chapter 10; March Advanced rganic Chemistry 4th ed., Chapters 5, ; otes: Augment your notes from 2nd/3rd year lectures to ensure they include the following: 1. Radical Generation: Thermolysis of weak bonds; otolysis of weak bonds; 1-electron redox chemistry; Chain processes; Selectivity and reactivity; Polar effects (nucleophilic and electrophilic radicals) and polarity matching 2. Synthesis with radicals: Reactions between radicals and non-radicals; Reactions between radicals and other radicals; Types of reactions (addition, substitution, elimination, rearrangement, electron transfer (S R 1); Use in making C-C, C- and C-al bonds; Stereochemical effects; Cyclisations and Baldwin s Rules. 3. Specific Topics: Bu 3 Sn reductions; Barton-thiohydroxamic esters; Barton-remote functionalisation (nitrite ester photolysis); Radicals in aromatic substitution e.g. diazonium salts + Cu(I); Kolbe synthesis; unsdiecker reaction; Fremy s salt; Birch reduction, acyloin reaction and reductive dimerisation of ketones. ther Reactive Intermediates Reading: Lecture otes (for reference when you have them); Reactive Intermediates, Moody and Whitham, CP no 8; Polar Rearrangements, L. M. arwood, CP no 5 Carbocations and Carbanions Structure and Reactivity a) Basics; susceptibility to nucleophiles / electrophiles, e- rich or poor species etc. b) Pyramidal inversion for C- and exceptions, planarity of C+. c) Evidence ego C+ - kinetics of S 1, solvent and substituent effects (ammet plots), crystal structures i.e. bond lengths and hyperconjugation, stable C+. d) Formation e.g. C- - S E 1, Lihalogen exchange, deprotonation etc. Reactions a) Rearrangements: concerted vs stepwise arguments (both C+ and C-). b) C- as nucleophiles, bases, reducing agents (via SET). Carbenes Structure and Reactivity a) singlet and triplet states b) substituent effects on reactivity c) evidence for structures i.e. matrix isolation, ESR etc Generation a) Diazo Compounds - stabilisation by carbenoid formation with TM complexes b) Tosylhydrazones - Bamford Stevens Reaction c) Ketenes - tendency to polymerise d) Strained Rings - eqm driven by relief of ring strain! 1!

2 e) Ylides - formal equivalents ie carbene transfer reagents f) Strained Alkenes - only if sterically unfavourable g) eterocycles - if provides stable fragment but needs high T h) a - Elimination - note ease of elimination I > Br > CI > F i) Simmons Smith Reaction stereospecificity Reactions a) Cycloadditions - Skell ypothesis - ring enlargement with aromatic compounds b) Insertion into C- - stereochemical consequence of singlet / triplet chemoselectivity - substituent effects c) Insertion into X- d) Rearrangements i) facile process due to electrophilic nature; ii)wolff rearrangement (use in Arndt Eistert Rxn); iii) Skattebol Rearrangement e) With ucleophiles - Ylid formation and Riemer Tiemann Rxn of phenoxides. itrenes - note similarity to carbenes Structure and Reactivity a) singlet and triplet states b) substituent effects on reactivity c) evidence - low T matrix isolation studies, ESR etc... Generation a) Azides Dor hn b) Isocyanates - hν only c) xidation of hydrazines - with Pb(IV), Mn2 etc d) Ylides e) Small rings - hν on oxaziridines f) eterocycles - if stable fragment formed g) Elimination - base mediated h) Reduction - of nitro / nitroso groups with P(III) Reactions a) Cycloadditions i. aziridine formation; ii. ring expansion with aromatics b) Insertion - selectivity of C- c) Rearrangements - possible involvement in rearrangement to electron deficient => ofmann, Lossen and Curtius rearrangements d) With nucleophiles - ylid formation Arynes Structure and Reactivity a) possibility of o- / m- / p- derivatives b) evidence for structures c) stabilisation by complexation Generation a) Aryl anions - isotopic labelling experiments, directing substituents b) Zwitterions c) Thermal / photochemical fragmentation - if form thermally stable fragment d) xidative Fragmentation e) Bergmann Cyclisation of 1, 3 enediynes! 2!

3 Reactions a) Cycloaddition - only if generated in the absence of a nucleophile; Diels Alder, Ene, [2+2] reactions etc 1,3 dipolar additions, trimerisation reaction etc b) ucleophilic addition i. order of reactivity; ii. with amines / phosphines etc; iii. steric / electronic substituent effects General Paper Questions (for old Q papers, try your college library) 99 I Q2 00 II Q4 01II Q4 02 I Q2 03 I Q3 04 I Q7 05 IB Q6 06 IB Q5 Also attached are some advanced problems: 99 Adv Q1 00 Adv Q6 AS 04 Adv Q1 Do these if you are happy with all the General paper questions.! 3!

4 99 Q2

5 2000 Q4. Give mechanisms for FIVE of the following reactions which proceed by radical intermediates: [5 x 4 marks] Br Ac Ac Bu 3 Sn AIB, toluene, heat Ac Ac + Ac Ac CCl ( 3 Si) 3 Si AIB, toluene, heat BuS, AIB toluene, heat C + SBu (d) (i) BS, (C 2 ) 2 (ii) 2 C 2 + C (e) S Br Bu 3 Sn, C, 80 atm, AIB, 100 C, C 6 6 S S S (f) (i) t BuCl (ii) h! (iii) a DCA Turn over

6 2001 Q4. Provide mechanisms for FUR of the following. [ 4 x 5 ] Bu 3 Sn Se AIB (trace) C 2 C 2 3 Sn (0.1 equiv.) AIB (trace) C 2 C 2 heat + (d) h! (e) + Pb(Ac) 4 2 C 2 Et C 2 Et 2704 DCA 4 Turn over

7 2002 Q2. Answer both part A and part B. Part A. Give mechanisms to explain how two of the following reagents initiate free radical reactions. [2! 2] C C 2 2 / Fe 2+ AIB Part B. Explain the chemistry in four of the following. [4! 4] 2 Cl CuCl Cl Boc 1) K then CS 2 then I 2) Bu 3 Sn, AIB (trace), " Boc TBDMS SnBu 3 I ( ) 5 2 AIB (trace) " TBDMS ( ) 5 2 (d) Bn Br AIB (trace) SnBu Bn 3 " (e) Et 2 C C 2 Et " (f) Cl h#, Et 3 TUR VER 2703 DCA 3

8 2003 Q3. Answer both part A and part B Part A. Give an account of the following characteristics of carbenes. [11] structure and spin state; stability; methods of generation. Part B. Give mechanisms for three of the following transformations which proceed by carbene/carbenoid intermediates. [3 x 3] Et 2 CC 2, heat C 2 Et Ts a, heat + CCl 3, t-buk Cl DCA 2703 Question continues 5

9 (d) heat (e) 2 hv in 2 C DCA 2703 TUR VER 6

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11 2005 Q6. Give mechanisms for five of the following processes, and comment on those factors which lead to the observed product outcome. [5 4] Br Sn 3 (2 eq.) AIB (trace), heat + Sn 3 (i) g(ac) 2, C 3 C 2 (ii) ab() 3 Ac Bu h Bu (d) Et Et Br + Bu 3 Sn C 2 Et AIB (trace), Bu 3 Sn (trace), heat Et Et C 2 Et (e) (trace) heat + (f) Se AIB (trace), Bu 3 Sn, heat DCC TUR VER

12 2006 Q5. Answer both Parts A and B of this question. Part A. utline the relevance of (i) steric, (ii) resonance and (iii) hybridisation effects upon the stability of carbon based radical intermediates. [4] Part B. Give mechanisms to rationalise the observed product outcome for four of the following reactions. [4! 4] (i) h! (ii) 3 + S Bu 3 Sn, trace AIB, heat Cl Bu 3 Sn, trace AIB, heat Cl (d) C 2 C 2 (i) BrC 2 Si 2 Cl, imidazole (ii) Bu 3 Sn, trace AIB, heat C 2 C 2 Si (e) (i) trace (RC) 2 2 [where R = C 3 (C 2 ) 1 0 ] BrCCl 3, heat (ii) K 2 C 3, heat CCl 3 DCC

13 Advanced 1999

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15 Ad. '00 6. Illustrate the use of free radicals as intermediates for carbon-carbon bond formation or cleavage. Your answer should include plausible reaction mechanisms, including comments on stereochemical aspects, for FIVE of the following examples [5 x 4] You should also include other illustrative examples of your own choice. [14] Si 3 Si 3 3 SnSn 3 C 2 Et h! C 2 Et S S h! Br Slow addition of Bu 3 Sn, AIB benzene, 80 o C (d) SiEt 3 Slow addition of Bu 3 Sn, AIB benzene, 80 o C SiEt 3 (e) Br Si 3 Bu 3 Sn, AIB benzene, 80 o C Si 3 Question continues DCA

16 (f) Si Br Bu 3 Sn, AIB benzene, 80 o C Si (g) Bu 3 Sn, AIB benzene, 80 o C TUR VER DCA

17 Adv Free radicals can be considered to possess either nucleophilic or electrophilic properties which can influence the outcome of their reactions. In this context, explain five of the following reactions, along with your own examples which illustrate the importance, or otherwise, of such polarity effects. [5! 5, + 9] 2 Br 2 (2 equiv.), hv!, heat C 8 8 Br 2 C 2 Et Et C 2 C 2 C 2 cat. S, heat Et Et (d) cat. Bu 3 Sn, trace AIB, heat (e) Se Bu 3 Sn, trace AIB, heat (f) Bu 3 SnSnBu 3 trace AIB, hv! (g) Bn trace SS, trace AIB, hv! Bn (h) C 2 C 2 trace BuSS, hv! 2 C C 2 DCA