S N 2 and E2 Mechanisms (strong base/nucleophile competition reacting at a carbon or reacting at a proton)

Transcription

1 Electrophile (Lewis Acid) = electron loving = any general electron pair acceptor (can also be an acidic proton = onsted acid) ucleophile (Lewis Base) = nucleus/positive loving = any general electron pair donor (can also be donated to an acidic proton = onsted base) Free adicals = one electron transfers, only limited examples are emphasized in our course (free radical substitution at sp 3 -, anti-markovnikov free radical addition reactions to pi bonds and some reactions with metals), Problems - upply the lone pairs, formal charge and the curved arrows to show how the electrons move for each step of a reaction mechanism. Be able to identify nucleophiles and electrophiles in each step of the reactions below. ur two free radical mechanisms (substitution at sp 3 - and anti-markovnikov addition to pi bonds) are at the end. heck your mechanisms against the examples provided. 2 and E2 Mechanisms (strong base/nucleophile competition reacting at a carbon or reacting at a proton) 1. ydroxide (available as a, K or ) Problem 3 3 a 1 a 3 3 E a alcohols methyl = only 2 primary = 2 > E2 secondary = E2 > 2 tertiary = only E2 2. Alkoxide (make with + a or make + a ) 3 Problem a 3 3 a 3 a E ethers methyl = only 2 primary = 2 > E2 secondary = E2 > 2 tertiary = only E2 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

2 2 3. arboxylates (make with 2 + a) 4. Potassium t-butoxide (make with ( 3 ) 3 + K) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

3 3 5. odium azide (available as a 3 ) a Problem azido compounds 2. Al 4 3. workup 1 o amines a azido compounds methyl = only 2 primary = mainly 2 secondary = mainly 2 tertiary = only E2 Follow up reaction = 2 reaction at nitrogen, followed by workup (protonates nitrogen) 2. workup Al o amines an also use the Gabriel amine synthesis (next). 6. Phthalimidate (make from phthalimide + a or K), Also called the Gabriel amine synthesis. Problem a a alkyl imide methyl = only 2 primary = mainly 2 secondary = mainly 2 tertiary = only E2 Follow up reaction = acyl substitution (twice) to make primary amines alkyl imide throw away a acyl substitution (twice) primary amine (also made by 1. a 3 2. Al 4 3. workup) acid base T.I. acid base acyl substitution T.I. y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

4 4 7. odium hydrogensulfide (available as a) 3 Problem a 2 3 a thiol methyl = only 2 primary = mainly 2 secondary = mainly 2 tertiary = only E2 8. odium alkylsulfide (make from + a) Problem a yanide (available as a) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

5 5 10. Terminal acetylides (make from terminal alkynes, + a 2 ) zipper reaction moves an internal triple bond () to the end position in unbranched chains where the negative charge is the most stable (in sp orbital). y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

6 6 11. Enolates (make from carbonyl compounds or nitriles + LA, -78 o to prevent side reactions) 3 Problem o 3 2 ketone enolate o methyl = only 2 2 primary = mainly 2 secondary = mainly 2 3 tertiary = only E2 2 ester enolate 2 nitrile enolate o 2-78 o There are many variations of this reaction on the enolate component and on the electrophilic component. 12. ithiane anion (made from dithiane + n-butyl lithium) Problem an repeat one more time. methyl = only 2 primary = mainly 2 secondary = mainly 2 tertiary = only E2 Follow up reaction = hydrolysis to carbonyl compound to make aldehydes or ketones. Think of g +2 as a giant proton for sulfur. 3. workup g +2 2 hydrolysis aldehyde or ketone g g discard g g 2 g g y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

7 7 13. uprates (made from / + u 2 u ) 3 Problem 2 u 3 u 3 3 methyl = only primary = mainly 2 secondary = mainly 2 tertiary = only E2 2 3 (for us) 3 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

8 1 / E1 possibilities extra complications at β positions of 2 o X, rearrangement to more stable 3 o + considered 8 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

9 9 (2,3) 2 same first step for 1/E1 2 add nuclephile (top/bottom) = 1 (3) lose - (top/bottom) = E rearrangement to similar or 3 3 more stable carbocation ( + ) edrawn (achiral) 3 stereochemistry is lost (start all over) carbocation choices 1 product (a. add from top and b. add from bottom), (without rearrangement), usually 1 > E1 (in our course) 2 3 b a (3) 3 b a (2,3) (2,3) 2 acid/base proton transfer acid/base proton transfer 3 diastereomers 3 (2,3) (2,3) 3 3 E1 product from left carbon atom (without rearrangement) 2 2 rotate rotate 3 3 "" parallel to empty2porbital on top (3) 3 E1 3 3 "" parallel to empty2porbital same alkene on bottom E1 2 (3) E1 product from right carbon atom (without rearrangement) 3 2 bond bond 3 2 (3) rotate bond (3) "" parallel to empty2porbital on top E1 "" parallel to empty2porbital on bottom E1 (rearrangement on next page) 3 3 (3) E-alkene diastereomers 3Z-alkene Both chiral centers are destroyed. y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

10 10 After rearrangement to 3 o carbocation ( + ) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

11 1. Water as a weak nucleophile/base with - (or X), makes alcohols by 1 (o reaction at methyl and 1 o ) 11 Problem c a=back 2 b=front 1 a 2 a rearrangement e (2 o to 3 o ) 2 E1 f d d 1 b E1 c c=f c' = not shown b d f=c e 2 achiral (top attack = bottom attack) 2. Alcohols as weak nucleophile/bases, makes ethers with - (or X) by 1 (o reaction at methyl and 1 o ) Problem E1 c = f rearrangement e 3 3 e 3 3 c d f 1 a b a 1 b 3 E1 c = f c d 3 achiral c' = not shown a b y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

12 12 3. arboxylic acids as weak nucleophile/bases, makes esters with - (or X) by 1 Alcohol reactions in strong acid (l,, I, 2 4, Ts are available): ( = 2 and 1), ( 2 4 / = E1) in our course. 1. Methyl and primary alcohols + 2 reactions (no rearrangement) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

13 13 2. econdary and tertiary alcohols + 1 reactions (possible rearrangement) 3. Methyl and primary alcohols + Pl 3 or P 3 2 reactions (no rearrangement) (PX 3 Lewis acids are available) 4. econdary and tertiary alcohols + Pl 3 or P 3 1 reactions (possible rearrangement) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

14 14 5. Methyl and primary alcohols + l 2 or 2 2 reactions (no rearrangement) (X 2 Lewis acids are available) 6. econdary and tertiary alcohols + l 2 or 2 1 reactions (possible rearrangement) Problem synthesis of an alkyl chloride from an alcohol + thionyl chloride (l 2 ) [can also make from 2 ] acyl-like substitution top/bottom attack 1 at secondary and tertiary alcohols 7. ow to avoid rearrangement at secondary (two steps, a. Tsl/pyridine b. a = 2) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

15 15 8. Alcohols / = E1 (alkene products, possible rearrangements) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

16 16 9. Alcohols + r 3 / 5 6 (P) (oxidizes primary to aldehyde and secondary to ketone) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

17 Alcohols + r 3 / 2 (Jones) (oxidizes primary to carboxylic acid and secondary to ketone) Problem primary alcohols 2 r r Jones = r 3 / 2 /acid primary alcohols oxidize to carboxylic acids (acidic water hydrates the carbonyl group, which oxidizes a second time ) 3 3 r r hydration of the aldehyde r E2 r aldehydes (continue in water) r 3 second oxidation of the carbonyl hydrate 2 r r r 3 2 carboxylic acids 3 2 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

18 11. TP protection of alcohols, + P (Ts cat.) TP ether, which can be deprotected with 2 4 / 2 18 Problem Ts TP protected alcohol 3 2 regenerated alcohol a. protection conditions - alkene addition reaction Ts P = dihydropyran TP ethers do not react under strong base/nucleophiles and neutral conditions (protected). They are hydrolyzed back to the alcohol under acid conditions (deprotected). TP = TP = tetrahydropyran protected alcohol b. deprotection conditions - aqueous acid conditions hydrolyzes acetal back to alcohol TP = tetrahydropyran protected alcohol desired alcohol etc. discard Epoxides in trong Base/ucleophile mixtures: backside attack at least hindered carbon. 1. ydroxide y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

19 19 2. Alkoxides 3. rganometallics ( and Mg) 4. Terminal acetylides Problem a workup a chiral center did not invert 5. yanide y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

20 20 6. thium aluminum hydride and sodium borohydride (or deuterides) 7. ithiane anion 8. Enolates y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

21 21 9. eactions with LA (lithium diisopropylamide = strong, bulky base removes a proton, made from diisopropylamine + n-butyl lithium) Epoxides in trong Acid/Electrophile mixtures 1. Aqueous acid 2. Alcohol + Ts y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

22 22 arbonyl Groups in trong Base/ucleophile mixtures Aldehydes 1. ydroxide hydration Problem a 3 2 a 3 attack from both faces equilibrium favors = a 3 equilibrium favors = and 3 carbonyl hydrate 2. Alkoxide hemi-acetal formation Problem a a 3 attack from both faces equilibrium favors = a equilibrium favors = 3 and 3 hemi-acetal 3. rganometallics ( and Mg reagents) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

23 23 4. Terminal acetylides 5. yanide Problem a 3 2. workup a 3 attack from both faces 3 and 3 6. thium aluminum hydride or sodium borohydride (or deuteride) 7. Enolates (with various electrophiles) Problem 2 3. workup workup y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

24 24 8. ithiane anion - reacts with various electrophiles, can react once (make aldehydes) or twice (make ketones) 2. Problem gl 2 / 2 3. gl 2 / 2 3. gl 2 / 2 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

25 9. ulfur ylid (make from a. diphenylsulfide + ( 2) b. sulfur salt + n-butyl lithium c. carbonyl compound) Ph Problem Ph n-butyl lithium Ph Ph Ph Ph 2 2 Ph 3 Ph Ph Ph 3 sulfur salt sulfur ylid Ph 3 Ph transispreferred 10. Phosphorous ylid (Wittig reaction = make from a. triphenylphosphine + ( 2) b. phosphorous salt + n-butyl lithium c. carbonyl compound) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

26 Wittig reaction that makes alkynes from aldehydes. (J..., 1982, 47, ) ( 3 ) P 1 Problem ( 3 ) n-butyl lithium 2 terminal alkyne 1 ( 3 ) P 2 ( 3 ) ( 3 ) P ( 3 ) P ( 3 ) ( 3 ) phosphorous salt terminal alkyne ( 3 ) ( 3 ) P ( 3 ) P ( 3 ) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

27 27 Ketones (and carbon dioxide) 1. ydroxide hydration 2. ydroxide with carbon dioxide makes bicarbonate makes carbonic acid (an inorganic example) Problem a 2 acidify a attack from both faces 3. Alkoxide makes hemi-ketal Problem a equilibrium favors = a bicarbonate equilibrium favors = carbonic acid a equilibrium 2 favors = 3 attack from both faces a equilibrium favors = and hemi-ketal 3 4. rganometallics ( and Mg reagents) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

28 28 5. rganometallics ( and Mg reagents) + 2 (special carbonyl) 2. workup 6. Terminal acetylides 7. yanide 8. thium aluminum hydride (more reactive) or sodium borohydride (less reactive) ( or deuterides) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

29 29 9. Enolates - many variations Problem o 2. workup 3. workup workup o workup workup ithiane anion many variations Problem gl 2 / 2 3. gl 2 / 2 3. gl 2 / 2 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

30 11. ulfur ylid (make from a. diphenylsulfide + ( 2) b. sulfur salt + n-butyl lithium c. carbonyl compound) Phosphorous ylid (Wittig reaction = make from a. triphenylphosphine + ( 2) b. phosphorous salt + n-butyl lithium c. carbonyl compound) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

31 31 Esters (and carbonates) 1. ydroxide (hydrolysis is also called saponification = soap making) Problem ' ester ester ' overall = acyl substitution addition ' elimination tetrahedral intermediate = (T.I.) ' ' 2. Alkoxide (Transesterification) Problem 3 ester ' 3 ester ' the nucleophile attacks the electrophile ' elimination addition 3 tetrahedral intermediate = (T.I.) overall = acyl substitution 3 ' 3. rganometallics ( and Mg reagents) 3 2 ester the nucleophile attacks the electrophile tetrahedral intermediate (T.I.) 3 o alcohol with two identical groups at alcohol carbon. reaction option not possible to aldehydes and ketones elimination ethoxide similar energy to T.I. intermediate 2 2. workup overall = acyl substitution 3 2 ketone is more reactive than the ester y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

32 32 4. thium aluminum hydride or sodium borohydride (or deuteride) Al 4 Problem ' 2. workup ester overall = acyl substitution Al ester addition tetrahedral intermediate (T.I.) 1 o alcohol with two identical groups at alcohol carbon. elimination 2 2. workup Al aldehyde is more reactive than the ester 5. iisobutylaluminium hydride (IBA) 6. Amines 7. thium diisopropylamide (LA), run at -78 o y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

33 33 8. uprate reactions three variations for us that complement the lithium and magnesium organometallics y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

34 34 arbonyls (aldehydes, ketones, esters, amides, nitriles) in trong Acid/Electrophile mixtures 1. Aqueous acid makes carbonyl hydrates Problem arbonyl (aldehyde or ketone) + + Ts (- 2 ) makes hemi-acetals and acetals and hemi-ketals and ketals Problem 3 Ts 3 hemi-acetal Ts 3 (- 2 ) acetal Ts 3 3 Ts 3 hemi-acetal 3 3 acetal remove carbonyl favored by addition of water Ts 2 2 several steps 3 hemi-acetal several steps 3 acetal favored by removal of water y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

35 35 Problem Ts Making a ketal (acetals are similar) ketone Ts Ts Ts hemi-ketal ketal water controls the direction of equilibrium Problem 3 2 ydrolysis of a ketal back to a ketone and ethylene glycol (acetals are similar and go back to aldehydes and ethylene glycol) ketal ( 2 4 / 2 ) ketone y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

36 36 3. arbonyl (aldehyde or ketone) Ts (- 2 ) / p = 5, makes imines that can be reduced (a. a 3 B b. workup) to amines. Problem 2 Ts (- 2 ) 1. a 3 B 2. workup Making an imine from a ketone or aldehyde and 3, 2 or 2. Then making the imine into a 1 o, 2 o or 3 o amine using a 3 B and workup. ketone or aldehyde 3, 2 or 2 Ts p 5 (- 2 ) Ts Ts water controls the direction of equilibrium remove to for imine imine 2 educe imine to amine with 1. sodium cyanoborohydride and 2. workup B imine a Transformations = + 3 primary amines = + 1 o amines secondary amines = + 2 o amines tertiary amines a 2. workup 2 amine y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

37 37 4. arbonyl (aldehyde or ketone) Ts (- 2 ) / p = 5, makes enamine that can be alkylated and hydrolyzed back to a ketone y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

38 38 5. Fischer esterification ( using Ts as acid catalyst) Problem 3 Ts 3 (- 2 ) carboxylic acid Ts equilibrium is controlled by water, removing water shifts it to the right and adding water shifts it to the left 3 alcohol 3 Ts Ts 3 3 ester = 3 3 water can be distilled out and removed from the equilibrium 3 Ts 3 T.I. = B 6. y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

39 39 Acid chlorides (and chloroformates, phosgene and equivalents, sulfur, nitrogen and phosphorous) 1. Making an acid chloride (from 2 + l 2 ) 2. Alcohols make esters 3. Amines make amides y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

40 40 4. rganometallics ( and Mg reagents) make tertiary alcohols 5. thium aluminum hydride or sodium borohydride make primary alcohols 6. iisobutylaluminium hydride (IBA) makes ketones 7. arboxylic acids make anhydrides 8. Water remakes the carboxylic acid (not desired) 9. Aromatics + All3 makes aromatic ketones 10. uprates make ketones Anhydrides (organic and mixed) 1. ydroxide 2. Alkoxide 3. rganometallics ( and Mg reagents) 4. thium aluminum hydride or sodium borohydride 5. iisobutylaluminium hydride (IBA) 6. Amines 7. thium diisopropylamide (LA) 8. Acids 1. ydroxide 2. Alkoxide 3. rganometallics ( and Mg reagents) 4. thium aluminum hydride or sodium borohydride 5. iisobutylaluminium hydride (IBA) 6. Amines 7. thium diisopropylamide (LA) 8. y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

41 41 Amides (primary, secondary and tertiary) 1. ydroxide 2. Alkoxide 3. rganometallics ( and Mg reagents) 4. thium aluminum hydride or sodium borohydride 5. iisobutylaluminium hydride (IBA) 6. Amines 7. thium diisopropylamide (LA) 8. itriles 1. ydroxide 2. Alkoxide 3. rganometallics ( and Mg reagents) 4. thium aluminum hydride or sodium borohydride 5. iisobutylaluminium hydride (IBA) 6. Amines 7. thium diisopropylamide (LA) 8. arbonyl Groups in trong Protic or Lewis Acid onditions 7. Aldehydes 8. Ketones (and carbon dioxide) 9. Esters (and carbonates) 10. Acid chlorides (and chloroformates, phosgene and equivalents, sulfur, nitrogen and phosphorous) 11. Anhydrides (organic and mixed) 12. Acids y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

42 Amides (primary, secondary and tertiary) 14. itriles 15. Miscellaneous (Various name reactions) 1. Baeyer Villigar reaction 2. Iodoform reaction 3. itrile synthesis from primary amide and l 2 synthesis of a nitrile from an 1 o amide + thionyl chloride (l 2 ) l l l l l l l l Base l l l l l l Base y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

43 43 4. ydrolysis of nitriles (moderate acid makes 1 o amide, strong acid/heat makes carboxylic acids) l / 2 hydrolysis of a nitrile to an amide (in 2 4 / 2 / hydrolysis continues on to a carboxylic acid) hydroxamic acid 3 1 o amides stop here in l/ 2 (continue on in 2 4 / 2 ) 3 3 see structures directly above carboxylic acids (in 2 4 / ) most stable cation drives equilibrium to completion 5. itter reaction y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

44 uprates IBA itriles Thionyl chloride y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

45 methyl = only 2 methyl = only 2 primary = 2 > E2 secondary = E2 > 2 primary = mainly 2 secondary = mainly 2 tertiary = only E2 tertiary = only E2 a Al 2 methyl = only 2 primary = 2 > E2 secondary = 2 > E2 tertiary = only E2 methyl = only 2 primary = 2 > E2 secondary = 2 > E2 tertiary = only E workup primary alcohol pk a = water is a good leaving group 2 no rearrangement primary bromoalkane y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

46 46 a b I I I I c 2 d I I e 3 2. workup l l f a a 2. workup 2 l 2 l g a a 2. workup 2 2 h l l 3 3 l 3 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

47 47 i 3 There isn't any lone pair, so you have to use the pi electrons as the nucleophile j a little tricky, requires 3 arrows to make bridge k a little tricky, requires 3 arrows 2 l ydrolysis of a ketal back to a ketone and ethylene glycol (acetals are similar and go back to aldehydes and ethylene glycol) common name = functional group = ( 2 4 / 2 ) emove 2 shifts equilibrium to the Adding 2 shifts equilibrium to the y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

48 48 m ester base hydrolysis = saponification a a a ester carboxylic acid 2. workup (neutralize carboxylate) alcohol a n ester synthesis from acyl substition at an acid chloride with an alcohol l acid chloride l l l o secondary amide synthesis from acyl substition at an acid chloride with a primary amine l l acid chloride l l p synthesis of an acid chloride from an acid + thionyl chloride (l 2 ) l l l l l l l l Base l l l l l l acylium ion Base y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

49 49 q synthesis of an alkyl chloride from an alcohol + thionyl chloride (l 2 ) [can also make from 2 ] 2 l l 2 l l 2 l l Base Base 2 at methyl and primary alcohols l 2 l l 2 l r synthesis of an alkyl chloride from an alcohol + thionyl chloride (l 2 ) [can also make from 2 ] l l l l Base l l Base 1 at secondary and tertiary alcohols l l l l r 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 Base l l Base y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

50 50 s 3 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 ) t 3 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 ) s 3 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 ) y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

51 51 t 3 There isn't any lone pair, so you have to use the pi electrons as the nucleophile ( 3 / Ts) 3 ether synthesis from an alkene with alcoholic acid form most stable carbocation ( rearrangements are possible ) l ydrolysis of a ketal back to a ketone and ethylene glycol (acetals are similar and go back to aldehydes and ethylene glycol) common name = functional group = ( 2 4 / 2 ) emove 2 shifts equilibrium to the Adding 2 shifts equilibrium to the y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

52 52 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc l / 2 hydrolysis of a nitrile to an amide (in 2 4 / 2 hydrolysis continues on to a carboxylic acid) i 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

53 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 secondary alcohols r 3 2 r r 3 P = pyridinium chlorochromate oxidation of secondary alcohol to a ketone r ketones y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

54 primary alcohols 2 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 ) r hydration of the aldehyde 3 3 r 3 second oxidation of the carbonyl hydrate 2 2 aldehydes 2 r r 54 r r r y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

55 55 a a a a a a too many side reactions poor yields y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

56 56 Al a B Al 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) P: base = pyridine Jones: base = water 3 2 r aldehydes eaction continues with aldehydes, IF in water (= Jones). 3 2 aldehyde (from 1 o alcohol) carbonyl hydrate 3 2 r 3 2 carboxylic acids r r r y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

57 57 Possible Keys heck for mistakes. I often make a few with all of the necessary computer clicks. a b I I I I c 2 d I I e 3 2. workup l 2 l f a a l 2. workup 2 2 l g 2. workup 2 2 h l 3 3 from best + 3 l l y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

58 58 i There isn't any lone pair, so you have to use the pi electrons as the nucleophile. 3 3 j a little tricky, requires 3 arrows to make bridge k a little tricky, requires 3 arrows water is better than bromide 2 l Making a ketal (acetals are similar) Ts Ts functional group = ketone Ts common name = hemi-ketal ketal common name = emove 2 shifts equilibrium to the right Adding 2 shifts equilibrium to the left y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

59 59 m ester base hydrolysis = saponification a a a ester carboxylic acid 2. workup (neutralize carboxylate) alcohol a n ester synthesis from acyl substition at an acid chloride with an alcohol ester l acid chloride l l l o secondary amide synthesis from acyl substition at an acid chloride with a primary amine acid chloride l l l l 2 o amide p synthesis of an acid chloride from an acid + thionyl chloride (l 2 ) l l l l l l l l Base l l l l l l acylium ion Base y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

60 Problem - Identify the nucleophile (Lewis base) and the electrophile (Lewis acid) in each equation and show the products of the following reactions. Add the curved arrows to show how each reaction proceeds. 60 a b I c d I e 3 I f g l y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

61 61 h react with carbon i react with proton j k 3 l m n 3 3 Problem - Which of the structures below can be a Lewis acid (show an arrow pushing reaction with base B:), a Lewis base (show a reaction with acid A) or both an acid and a base (show both reactions)? l 3 y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

62 62 1. Mechanism for free radical substitution of alkane sp 3 - bonds to form sp 3 - bonds at weakest - position overall reaction 1. initiation 2a propagation 3 2 weakest bond ruptures first h 3 h BE = +95 kcal/mole BE = -88 kcal/mole = +7 kcal/mole (overall) = 46 kcal/mole = -15 2b propagation BE = +46 kcal/mole BE = -68 kcal/mole = -22 kcal/mole (overall) both steps 3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrations 3 = -68 kcal/mole very minor product 3 = -80 kcal/mole 2. Free radical addition mechanism of - alkene pi bonds (alkenes can be made from E2 or E1 reactions at this point in course) (anti-markovnikov addition to alkenes) overall reaction (cat.) h initiation (two steps) 2a propagation 3 2 (cat.) h reagent 3 2 = 40 kcal/mole BE = +88 kcal/mole BE = -111 kcal/mole = -23 kcal/mole BE = +63 kcal/mole BE = -68 kcal/mole = -5 kcal/mole y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc

63 63 2b propagation BE = +88 kcal/mole BE = -98 kcal/mole = -10 kcal/mole = -15 both steps (2a + 2b) r a 2 a Al B a y:\files\classes\315\315 andouts\arrow pushing mechs & rxn summary.doc