Electrophile = electron loving = any general electron pair acceptor = Lewis acid, (often an acidic proton)

Transcription

1 314 Arrow Pushing practice/eauchamp 1 Electrophile = electron loving = any general electron pair acceptor = Lewis acid, (often an acidic proton) ucleophile = nucleus/positive loving = any general electron pair donor = Lewis base, (often donated to an acidic proton) Problems - n 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). upply the lone pairs, formal charge and the curved arrows to show how the electrons move for each step of the reaction mechanism. dentify 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 get to it. Let me know when you find errors. reactions Examples of important patterns to know from our starting points (plus a few extras). methyl and primary secondary tertiary special 3 very good 2 patterns very poor 2,E2, 1,E1 allylic vinyl benzylic phenyl There are many variations. 1 o neopentyl 1. 2 and 2 a b 2. 2 and E2 a b 3. 2 and 2 a a b a a a Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

2 314 Arrow Pushing practice/eauchamp and acyl substitution a make alkyl imide a further reaction with a 2 acyl substitution primary amine mech. - not shown make imidate nucleophile a a 5. E2 and 2 a 2 b E2 > 2 2 > E2 6. E2 reactions a 2 b E2 >> 2 E2 >> 2 7. E2 and 2 a K K b K K E2 >> make potassium t-butoxide K potassium hydride (always a base) 8. ucleophilic hydride = sodium borohydride (a 4 ) and lithium aluminum hydride (Al 4 = LA), [deuterium is used below to show reaction site] 2 reaction a b Al a Al a K Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

3 314 Arrow Pushing practice/eauchamp 3 9. Alkyl carbanions (lithium and magnesium) are poor nucleophiles with compounds, [cuprates work well] a b poor yields, too 2 many side reactions E2 and E2 and acid/base 11. E2 and E2 and acid/base 3 a 2 a and E1 possibilities (1. rearrangement, 2. add nucleophile, 3. lose beta proton) a a a poor yields, too many side reactions a E/Z E/Z 2 / Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

4 314 Arrow Pushing practice/eauchamp 4 Alcohol eactions Examples of important patterns to know in our course (plus a few others). methyl and primary secondary tertiary special 3 allylic vinyl - enol is unstable, keto tautomer preferred benzylic phenyl There are many variations. 1 o neopentyl ( 2 at methyl and primary and 1 at secondary, tertiary, allylic and benzylic in our course) , and E1 are possible here, but not shown. E1 + 1 no / Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

5 314 Arrow Pushing practice/eauchamp Thionyl chloride = acyl-like substitution, then 2 synthesis of an alkyl chloride from an alcohol + thionyl chloride (l 2 ) [can also make from 2 ] l l 2 l l 2 l l 2 at methyl and primary alcohols l 2 l o rearrangement because no +. l 2 l l 15. Thionyl chloride = acyl substitution, then 1 synthesis of an alkyl chloride from an alcohol + thionyl chloride (l 2 ) [can also make from 2 ] l l l l l l 1 at secondary and tertiary alcohols / l l l l 16. Phosphorous tribromide (P 3 ) = 2, then 2 (at methyl and primary ) P P P reacts twice more 17. Phosphorous tribromide (P 3 ) = 2, then 1 (at secondary, tertiary, allylic and benzylid ) P P P reacts twice more, Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

6 314 Arrow Pushing practice/eauchamp r= addition, acid/base and E2 to form = (aldehydes and ketones) 3 2 primary alcohols r 3 2 r 3 2 r P = pyridinium chlorochromate oxidation of primary alcohol to an aldehyde (no water to hydrate the carbonyl group) 3 2 r aldehydes 19. r= addition, acid/base and E2 to form = (aldehydes and ketones) secondary alcohols r 3 2 r r 3 P = pyridinium chlorochromate oxidation of primary alcohol to an aldehyde (no water to hydrate the carbonyl group) r ketones Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

7 314 Arrow Pushing practice/eauchamp r= addition, acid/base and E2 to form =, then hydration of = and repeat reactions primary alcohols 2 r 3 2 Jones = r 3 / 2 / acid primary alcohols oxidize to carboxylic acids (water hydrates the carbonyl group, which oxidizes a second time ) 3 2 r hydration of the aldehyde r r 2 aldehydes (cont. in water) r 3 second oxidation of the carbonyl hydrate 2 r r r 3 2 carboxylic acids Formation of alkoxide from + a or K (acid/base reaction) a a a Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

8 314 Arrow Pushing practice/eauchamp ehydration to alkene (E1) from / (possibility of rearrangements) Water ends up as 3 + in 2 4. Water ends up as 3 + in 2 4. nly the major alkene is shown. 23. Formation of esters from + acid chlorides l l l There are many variations of and 2 joined together by oxygen. l Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

9 314 Arrow Pushing practice/eauchamp Formation of tosylates from + Tsl (toluenesulfonyl chloride = tosyl chloride), /E chemistry is possible l l l l l, (racemic) compare 1. Tsl/pyridine 2. al (prevents + formation and any rearrangement) l separate step l a l alkyl tosylate = compound Epoxide reactions Examples of important patterns to know from our starting materials. 25. We can make epoxides from alkenes using 1. 2 / 2, 2. a. (Later from mpa too.) step 1 - make bromohydrin bromohydrin step 2 - make epoxide by reacting with epoxide synthesis from bromohydrin mild base bromohydrins epoxides Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

10 314 Arrow Pushing practice/eauchamp like attack at less hindered epoxide carbon, and workup (overall addition) a a 2 hydroxide 2 a a 2 alkoxides (ethoxide) 2 a terminal acetylide a 2 2 a cyanide a n-butyl lithium ucleophilic hydride = sodium borohydride (a 4 ) and lithium aluminum hydride (Al 4 = LA), [deuterium is used below to show reaction site] a 2 a sodium borodeuteride sodium borhydride 2 Al lithium aluminium deuteride lithium aluminium hydride (LA) 2 2 Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

11 314 Arrow Pushing practice/eauchamp Epoxide reactions in acid conditions. (compare to base reaction) ur only E2 reaction for epoxides. Uses very basic, sterically bulky LA (always a base). 3 3 (compare to base reaction) LA = lithium diisopropylamine (always a base) allylic alcohols Aldehyde and Ketone reactions Examples of important patterns to know. methanal (formaldehyde) We can make aldehydes and ketones from alcohols and alkynes (for now). 30. = addition with organolithium reagent, and workup aldehyde n-butyl lithium / 2 2 o alcohol 2 Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

12 314 Arrow Pushing practice/eauchamp 12 2 aldehydes or ketones 3 organolithium or organomagnesium reagents 3 l 2 2 o or 3 o alcohols 3 l 31. = addition with cyanide forming cyanohydrin aldehyde or ketone a terminal acetylide a 2 l propargylic alcohols 2 l 32. = addition with cyanide forming cyanohydrin aldehyde or ketone a a l 2 cyanohydrins 33. ucleophilic hydride = sodium borohydride (a 4 ) and lithium aluminum hydride (Al 4 = LA), [deuterium is used below to show reaction site] aldehyde a sodium borodeuteride sodium borhydride a 2 2 l 2 1 o alcohol otice: was nucleophilic hydrogen and (on ) was electrophilic hydrogen ketone a sodium borodeuteride sodium borhydride a / o alcohol otice: was nucleophilic hydrogen and (on ) was electrophilic hydrogen Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

13 314 Arrow Pushing practice/eauchamp ydration of = in acid or base conditions (also tautomerization conditions, competing reactions) ydration of = is similar to making acetals and ketals and hydrolysis of esters acid conditions base conditions 35. Ketone to hemi-ketal to ketal and aldehyde to hemi-acetal to acetal (protects = as ether during other reactions conditions) Making a ketal (acetals are similar) Ts Ts functional group = ketone Ts common name = hemi-ketal common name = water controls the direction of equilibrium emove 2 shifts equilibrium to the Adding 2 shifts equilibrium to the 36. eprotection of ketal (acetal) to regenerate ketone or aldehyde, 1 reaction, then E1 reaction to form = (deprotection of a ketone or aldehyde) Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

14 314 Arrow Pushing practice/eauchamp 14 Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc common name = emove 2 shifts equilibrium to the Adding 2 shifts equilibrium to the functional group = ydrolysis of a ketal back to a ketone and ethylene glycol (acetals are similar and go back to aldehydes and ethylene glycol) l ( 2 4 / 2 )

15 314 Arrow Pushing practice/eauchamp 15 arboxylic acids and derivatives reactions Examples of important patterns to know. methanoic acid (formic acid) Ph Ph methanoate esters (formic esters) Ph Ph Ph methanamides (formamides) Ph methanoyl chloride is not stable l l l l Ph l Ph l We can make carboxylic acids from alcohols, aldehydes and nitriles (for now). 37. ase hydrolysis of esters ester base hydrolysis = saponification ester a a a carboxylic acid (neutralize carboxylate) alcohol a Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

16 314 Arrow Pushing practice/eauchamp acid chloride + = esters (notice two different groups joined together by an oxygen) ester synthesis from acyl substition at an acid chloride with an alcohol l acid chloride l l 39. acid chloride + 2 = 2 o amides (notice two different groups joined together by a nitrogen) secondary amide synthesis from acyl substition at an acid chloride with a primary amine l acid chloride l l ynthesis of acid chlorides, acyl substitution, twice synthesis of an acid chloride from an acid + thionyl chloride (l 2 ) l l l l l l l l ase l l l acylium ion l l ase l Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

17 314 Arrow Pushing practice/eauchamp acyl substitution, then two elimination reactions synthesis of a nitrile from an 1 o amide + thionyl chloride (l 2 ) l l l l l l l l l l l l ase l l ase Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

18 314 Arrow Pushing practice/eauchamp 18 Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc 42. addition reaction (hydration) to imidate, tautomers to amide, acyl substitution to carboxylic acid l / 2 hydrolysis of a nitrile to an amide (in 2 4 / 2 hydrolysis continues on to a carboxylic acid) 3 3 stop here in l/ 2 (continue on in 2 4 / 2 ) 3 see structures directly above most stable cation drives equilibrium to completion hydroxamic acid 1 o amides carboxylic acids (in 2 4 / )

19 314 Arrow Pushing practice/eauchamp 19 Alkene and Alkyne reactions Examples of important patterns to know. other patterns showing regioselectivity and stereoselectivity alkynes We can make alkenes from and and alkynes from 2 (for now). 43. = addition reaction with -l (- and - are similar), Markovnikov addition forms most stable carbocation l 3 l 3 l = aqueous acid hydration reaction, goes via top/bottom addition (hydration of an alkene) There isn't any lone pair, so you have to use the pi electrons as the nucleophile hydration of an alkene with aqueous acid form most stable carbocation ( rearrangements are possible ) Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

20 314 Arrow Pushing practice/eauchamp = addition reaction (hydration of an alkene), with rearrangement There isn't any lone pair, so you have to use the pi electrons as the nucleophile hydration of an alkene with aqueous acid form most stable carbocation ( rearrangements are possible ) = addition reaction (ether synthesis from an alkene by addition of alcohols) There isn't any lone pair, so you have to use the pi electrons as the nucleophile ( 3 / Ts) 3 hydration of an alkene with aqueous acid form most stable carbocation ( rearrangements are possible ) = addition reaction (ether synthesis from an alkene by addition of alcohols), with rearrangement There isn't any lone pair, so you have to use the pi electrons as the nucleophile ( 3 / Ts) 3 3 ether synthesis from an alkene with alcoholic acid form most stable carbocation ( rearrangements are possible ) Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

21 314 Arrow Pushing practice/eauchamp ydration of alkynes (Markovnikov addition forms most stable carbocation), enol intermediate tautomerizes to keto tamtomer. There isn't any lone pair, so you have to use the pi electrons as the nucleophile omination of alkenes, goes via anti addition a little tricky, requires 3 arrows to make bridge bridging cation prevents rearrangement, attack at more partial positive carbon = addition reaction 3 3 no rearrangement alkenes / alkynes because of bridging cation 50. omhydrin formation from alkenes, goes via anti addition bromide attacks at more partial positive carbon 3 stereoselective = anti addition regioselective = none a little tricky, requires 3 arrows bridging cation prevents rearrangement, attack at more partial positive carbon water attacks at more partial positive carbon 2 bromohydrins form epoxides in mild base Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

22 314 Arrow Pushing practice/eauchamp 22 = addition reaction stereoselective = anti addition regioselective = Markovnikov alkenes / alkynes no rearrangement because of bridging water attacks at more cation partial positive carbon ydroboration of alkenes = anti-markovnikov addition (opposite regioselectivity to normal hydration conditions) anti-markovnikov addition to = (hydration makes alcohols), two steps: / step 1 = concerted addition to = by borane alkenes twice more trialkylborane step 2 = oxidation by hydrogen peroxide and rearrangement to anti-markovnikov alcohol trialkylborane anti-markovnikov alcohol twice more Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

23 314 Arrow Pushing practice/eauchamp ydroboration of alkynes = anti-markovnikov addition (opposite regioselectivity to normal conditions) anti-markovnikov addition to (hydration makes aldehydes), two steps: / step 1 = concerted addition to by dialkylborane alkenes = sterically large group so addition only occurs once step 2 = oxidation by hydrogen peroxide and rearrangement to anti-markovnikov aldehyde trialkylborane enolate = anti-markovnikov aldehyde Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc

24 314 Arrow Pushing practice/eauchamp Z:\classes\315\315 andouts\arrow pushing mechs, probs.doc