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Often an Acidic Proton) 314 Arrow Pushing practice/Beauchamp 1 Electrophile = electron loving = any general electron pair acceptor = Lewis acid, (often an acidic proton) Nucleophile = nucleus/positive loving = any general electron pair donor = Lewis base, (often donated to an acidic proton) Problems - In the following reactions each step has been written without the formal charge or lone pairs of electrons and curved arrows. Assume each atom follows the normal octet rule, except hydrogen (duet rule). Supply the lone pairs, formal charge and the curved arrows to show how the electrons move for each step of the reaction mechanism. Identify any obvious nucleophiles and electrophiles in each of the steps of the reactions below (on the left side of each reaction arrow). A separate answer file will be created, as I get to it. Let me know when you find errors. RX reactions Examples of important patterns to know from our starting points (plus a few extras). methyl and primary secondary tertiary special H3C X very good very poor SN2 patterns SN2,E2,SN1,E1 X X X X X vinyl allylic X X X X X X X benzylic X phenyl X X There are many X variations. X 1o neopentyl 1. SN2 and SN2 a b I Br Br N C I I C I N 2. SN2 and E2 a b H Br H O HC C H I HC C Br OH I 3. SN2 and SN2 a Na b Na Na Br S HC C Br Br O O S Na Br R R Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 2 4. SN2 and acyl substitution O O Na Na Br further reaction with NaOH N N Br H2N acyl substitution alkyl imide primary amine make O O mech. - not shown make imidate nucleophile O O O H Na N H N O Na O 5. E2 and SN2 a H b H2O O O I H O Br Br E2 > SN2 I SN2 > E2 O O R S 6. E2 reactions a H b H H2O O I H O Br E2 >> S 2 I Br N O E2 >> SN2 7. E2 and SN2 a b K K K K Br I Br H3C O O I SN2 O E2 >> SN2 make potassium t-butoxide K K H H O O potassium hydride (always a base) 8. Nucleophilic hydride = sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4 = LAH), [deuterium is used below to show reaction site] – SN2 reaction D a D B D b D Al D Na Br D Li D B D D I D D Al D Br D D I Na Li D D Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 3 9. Alkyl carbanions (lithium and magnesium) are poor nucleophiles with RX compounds, [cuprates work well] a b H2 H2 C CH2 C CH2 H C C Br poor yields, too Br poor yields, too 3 many side reactions H3C C H2 H2 many side reactions Li Li 10. E2 and E2 and acid/base R2N Br Br Br Br R N H Br Na 2 Na H H C H C C C H C H C C H C NR2 H NR2 H H NR H H H NR2 Na 2 11. E2 and E2 and acid/base R N 2 R2N H Br Br Br Br Br Na Na CH Na H C H C 3 CH3 C CH3 C CH3 H NR2 H H NR H H H NR2 NR2 2 12. SN1 and E1 possibilities (1. rearrangement, 2. add nucleophile, 3. lose beta proton) Br H H Br H H O H H E/Z H H H H H H O H H H H E/Z H O O H H H H O H2O H H R/S O Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 4 Alcohol Reactions Examples of important patterns to know in our course (plus a few others). methyl and primary secondary tertiary special H3C OH OH OH vinyl - enol is OH OH OH unstable, allylic keto tautomer preferred OH OH OH OH OH OH benzylic OH OH phenyl OH OH There are many variations. OH OH 1o neopentyl 13. HX + ROH (SN2 at methyl and primary ROH and SN1 at secondary, tertiary, allylic and benzylic ROH in our course) Br H H H Br O O O + H3O H Br H H + Br H H H3O O H H O O R H Br H Br Br H R,S Br H H + H3O O H H H O O R H H H Br H H Br Br SN1 and E1 are possible here, but H not shown. H Br E1 + SN1 no R/S Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 5 14. Thionyl chloride = acyl-like substitution, then SN2 synthesis of an alkyl chloride from an alcohol + thionyl chloride (SOCl2) [can also make RBr from SOBr2] O H O O Cl 2 S C Cl H 2 S R O H S C Cl R O R O Cl Cl H H Cl O No rearrangement Cl O Cl because no R+. S 2 at methyl and S H2 N C S primary alcohols O Cl Cl CH2 R O R H Cl 15. Thionyl chloride = acyl substitution, then SN1 synthesis of an alkyl chloride from an alcohol + thionyl chloride (SOCl2) [can also make RBr from SOBr2] O O Cl O S Cl S O Cl H S O R O Cl Cl R H Cl R H O O Cl S SN1 at secondary and Cl S tertiary alcohols O Cl O H H R R/S H Cl 16. Phosphorous tribromide (PBr3) = SN2, then SN2 (at methyl and primary ROH) Br Br Br H P P P O Br Br O Br O Br Br reacts S S Br H S twice H more 17. Phosphorous tribromide (PBr3) = SN2, then SN1 (at secondary, tertiary, allylic and benzylid ROH) Br Br Br P H P P Br Br O Br O O Br reacts R R Br H twice H Br H more Br R,S Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 6 18. Cr=O addition, acid/base and E2 to form C=O (aldehydes and ketones) O N H O O N O H H Cr O Cr O O O O O Cr H3C C O O H3C C H3C C C H C H H H C H 2 H 2 H H 2 H primary alcohols N PCC = pyridinium chlorochromate oxidation of primary alcohol to an aldehyde (no water to O hydrate the carbonyl group) O O N H Cr O H3C C C H H2 aldehydes 19. Cr=O addition, acid/base and E2 to form C=O (aldehydes and ketones) O N H O O N O H H Cr O Cr O O O O O Cr H3C C O O H3C C H3C C C CH3 C CH3 H H C CH3 2 H 2 H H 2 H secondary alcohols N O PCC = pyridinium chlorochromate oxidation O O of primary alcohol to an aldehyde (no water to Cr hydrate the carbonyl group) N H O H3C C C CH3 H2 ketones Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 7 20. Cr=O addition, acid/base and E2 to form C=O, then hydration of C=O and repeat reactions H O O O O O H O H Cr O H H Cr O O O H H O O Cr H3C C O O H3C C H3C C C H C H H H C H 2 H 2 H H 2 H primary alcohols Jones = CrO3 / H2O / acid H primary alcohols oxidize to carboxylic acids (water hydrates the carbonyl group, O which oxidizes a second time ) H H H H O O O O O O Cr H H resonance H C C O H3C C H3C C 3 C H C H C H H H2 H2 2 hydration of the aldehyde aldehydes (cont. in water) O H H H H H O O O H H H H O H O Cr H O O O O O H H H3C C O H3C C O Cr C H3C C O H H C O O 2 H H H C 2 H H H2 H second oxidation of the carbonyl hydrate H O O O O O Cr O H H Cr O O O H3C C H H C C O H C O 3 H C 2 H H2 H O carboxylic acids H H O H H 21. Formation of alkoxide from ROH + NaH or KH (acid/base reaction) Na H H Br Na Br H O H O O Na R R R Z:\classes\315\315 Handouts\arrow pushing mechs, probs.doc 314 Arrow Pushing practice/Beauchamp 8 22. Dehydration to alkene (E1) from ROH + H2SO4/∆ (possibility of rearrangements) H O H H O O O H O S OH H H O S OH H O H O H H O H H H O O Water ends up as O + O S OH HO SO H3O in H2SO4. H H O O O H H O S OH O O H H R R H O H H H O H O O S OH H O O H H H O Water ends up as O HO SO H O + O S OH H3O in H2SO4.
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