Chem 315/316 Reactions. Bromo organic compounds C1 & C2 carbon skeletons C3 carbon skeletons C4 carbon skeletons. Alcohols. Chem 316 / Beauchamp 1

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1 hem 316 / Beauchamp 1 hem 315/316 eactions Name available sources of carbon 4 3 NaN methyl 3 2 ethyl n-propyl 3 3 isopropyl n-butyl sec butyl t-butyl phenyl available until topic 13 omo organic compounds 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons 3 5 carbon skeletons 6 carbon skeletons ther patterns A few ways to make - (generic and specific) 2 hν free radical substitution weakest - = fastest rxn Me, 1 o = N 2 2 o, 3 o = N 1 also, P 3, 2 and 1. Tsl / py 2. Na Markovnikov addition 1. B / 3 anit-markovnikov addition 2 Fe 3 earrangements are possible with + intermediates. Alcohols 316 Z:\classes\315\315 andouts\functional group yn Probs1.doc

2 hem 316 / Beauchamp 2 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons 3 5 carbon skeletons 6 carbon skeletons ther patterns A few ways to make - Ns Me, 1 o = N 2 1 o 2 2 o, 3 o = N 1 possible rearrangement N 2 Ns acyl substitution Markovnikov addition (possible rearrangement) 1. B 3 1. gx 2 / / 2. NaB 4 1. Markovnikov addition ( rearrangement) anit-markovnikov addition 1 o o 3 o 1 o 2 o NaB 4 1. NaB 4 3 o 1 o 2 o 1. Al 4 1 o 3 = throw away 1. Al 4 1 o = throw away 1. Al 4 1 o 1. Al 4 There's even more ways, but this is eugh for w. earrangements are possible with + intermediates. Z:\classes\315\315 andouts\functional group yn Probs1.doc

3 hem 316 / Beauchamp 3 Ethers 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons 3 5 carbon skeletons 6 carbon skeletons ther patterns A few ways to make - Na 2 1. gx 2 / 2. NaB 4 Me, 1 o = N 2 2 o, 3 o = N 1 possible rearrangements Markovnikov addition (possible rearrangement) Markovnikov addition ( rearrangement) = a second carbon pattern Z:\classes\315\315 andouts\functional group yn Probs1.doc

4 hem 316 / Beauchamp 4 Amines 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons N N N 2 N 2 N 2 N 2 N 2 N 2 5 carbon skeletons N 2 N 2 N 2 N 2 N 2 N 2 N 2 6 carbon skeletons N 2 N 2 N 2 N 2 N 2 N 2 N 2 N2 N 2 N 2 N 2 N 2 N 2 N 2 N 2 N 2 N 2 ther patterns N 2 N 2 N 2 N 2 N 2 us N 2 N 2 A few ways to make -N 2 (1 o, 2 o, 3 o amines) 1. phthalimidate (from phthalimide + Na) 2. Na 1. N 2 (p = 5) 2. Na 3 BN N 2 o amine 1 o amine N 1. NaN 2 3 N 2 2. Al N (p = 5) 2. Na 3 BN (or Pd/ 2 ) N 3 o amine 1. N 3 (p = 5) 2. Na 3 BN N 2 1 o amine 1 o amine 1 N 1. Al 4 2 N 2 1 1, 2 = = 1 o amine 1 =, 2 = = 2 o amine 1, 2 = = 3 o amine N 1. Al4 N 2 1 o amine Z:\classes\315\315 andouts\functional group yn Probs1.doc

5 hem 316 / Beauchamp 5 Nitriles 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons N N N N N N 3 N N 5 carbon skeletons N N N N N N N 6 carbon skeletons N N N N N N N N N N N N N N N N N ther patterns N N N N N us N N A way to make -N NaN Me, 1 o, 2 o = N 2 N N 3 1 o amine (a. Al 4 b. WK) 1 o amide (l/ 2 ) acid ( 2 4 / 2 / ) aldehyde (a. DIBA b. WK) ketone (a. Mg b. WK) N 2 1 o amides l 2 N good mechanism problem Z:\classes\315\315 andouts\functional group yn Probs1.doc

6 hem 316 / Beauchamp 6 Alkynes 2 carbon skeleton 3 carbon skeleton 4 carbon skeletons 5 carbon skeletons 6 carbon skeletons ther patterns A way to make ( = ) 2 eqs. 2 hν 1. excess. NaN excess. NaN 2 elated s 1. NaN = 1 o 1. NaN o 1. NaN o 1. NaN NaN NaN o 2 o 3 o 3 + / 2 (g +2 ) B / / 2 (g +2 ) 2 Pd/ Pd/ 2 quiline Na / N 3 1. NaN excess. NaN 2 (zipper rxn) ontinue with any of the s above. 1. NaN excess. NaN 2 (zipper rxn) Z:\classes\315\315 andouts\functional group yn Probs1.doc

7 hem 316 / Beauchamp 7 Thiols and ulfides 1 & 2 carbon skeletons 3 carbon skeletons 4 carbon skeletons () () 3 () () us () () () () 5 carbon skeletons () () () () () () () 6 carbon skeletons () () () () () us () () () () () () us () ther patterns () () () us () us () () () () () () () us () () A way to make - A way to make -- Ns Me, 1 o, 2 o = N 2 thiol Ns Me, 1 o, 2 o = N 2 sulfide Z:\classes\315\315 andouts\functional group yn Probs1.doc

8 hem 316 / Beauchamp 8 Aldehydes ( 2 ) n n = any number ( 2 ) n n = any number A few ways to make 2 r 3 /py P 1. 2 B / 2 N 1. DIBA l 1. DIBA ' 1. DIBA 1. 3, -78 o Ketones ( 2 ) n n = any number ( 2 ) n n = any number ' A few ways to make ' 2 r 3 /py P 1. 1 r 3 / 2 Jones or 1 r 3 /py P g g +2 2 N eqs. 1 1 l 1. 1 u 1. 3, -78 o l All 3 Z:\classes\315\315 andouts\functional group yn Probs1.doc

9 hem 316 / Beauchamp 9 arboxylic acids ( 2 ) n n = any number ( 2 ) n n = any number A few ways to make 2 2 r 3 / 2 Jones r 3 / 2 Jones 1. Mg N 2 l/ 2 1 o amide ' target ' throw away or throw away ' target 1. 3, -78 o / 2 x KMn 4 / (n -1) carbons l 2 (side rxn) ' N 2 1 o,2 o,3 o amides ' 2 N ' one is a keeper and one is a throw away Acid chlorides l l l l l l ( 2 ) n l n = any number l l l l l l l ( 2 ) n l n = any number A few ways to make l l 2 We use this one. l ll oxalyl chloride l anhydride ( 2 ) ester () 1 o amide (N 3 ) 2 o amide (N 2 ) 3 o amide ( 2 N) aldehyde ( 2 Al = DIBA) ketone ( 2 u + = cuprate) Z:\classes\315\315 andouts\functional group yn Probs1.doc

10 hem 316 / Beauchamp 10 Esters ( 2 ) n n = any number ( 2 ) n n = any number A few ways to make 2 ' ' 1. Na 2. X (X = Me,1 o,2 o ) ' ' l -- 3 N ' ' Ts (- 2 ) ' Fischer ester synthesis 2 4 Z:\classes\315\315 andouts\functional group yn Probs1.doc

11 hem 316 / Beauchamp 11 Products from s of carbon nucleophiles and carbon electrophiles used in our course: arbon electrophiles 3 methyl X orga reagents N (Mg) orga reagents N arbon and hydrogen nucleophiles Na Na N 2 u Al 4 Na B 4 acetylides cyanide cuprates (LA) alkynes nitriles 2 X coupling alkyls alkyls Al diisobutylaluminium hydride (DIBA) N primary X N N alkynes nitriles 2 X coupling alkyls alkyls N secondary X N N E2 nitriles 2 X coupling alkyls alkyls N ethylene oxide 1 o 1 o 1 o 1 o alkynes nitriles 1 o 1 o 1 o N propylene oxide 2 o 2 o 2 o 2 o alkynes nitriles 2 o 2 o 2 o N isobutylene oxide 3 o 3 o 3 o 3 o alkynes nitriles 3 o 3 o 3 o N methanal 1 o 1 o 1 o cyahydrin alkynes N methal methal N simple aldehydes 2 o 2 o 2 o alkynes cyahydrin N 1 o 1 o N simple 3 o 3 o 3 o alkynes cyahydrin unless sterically hindered N 2 o 2 o N simple esters 3 o 3 o (Nu: twice) (Nu: twice) N N 1 o (Nu: twice) 1 o N aldehydes simple carboxylic acids (B: once Nu: once) acid/base net rxn acid/base net rxn N acid/base net rxn acid/base net rxn acid/base net rxn acid/base net rxn l simple acid chlorides 3 o (Nu: twice) 3 o (Nu: twice) N N 1 o 1 o N N simple nitriles N N N 1 o amines (also amines from amides) N aldehydes (also aldehydes from 3 o amides) carbon dioxide carboxylic acids carboxylic acids carboxylic acids N N N N N α,β-unsaturated 3 o 3 o N conjugate addition WK = rmal workup to neutralize the. For the basic s (like above) above this would require mild acid neutralization ( 3 + ). N = or productive result or emphasized N alcohols alcohols N Z:\classes\315\315 andouts\functional group yn Probs1.doc

12 hem 316 / Beauchamp 12 ' ' (Mg) ' 2 u Na Al Na 4 B N Na 4 1 o 2 primary X alkyl coupling alkyne nitriles 1 o 2-1 o 2-2 o 2 secondary X epoxides (+2+) (+2+) alkyl coupling (+2+) E2 (+2+) nitriles (+2+) 2 o 2-2 o 2-2 methanal 1 o 1 o 1 o 1 o methal methal aldehydes 2 o 2 o 2 o 2 o 1 o 1 o 2 3 o 3 o 3 o 3 o 2 o 2 o carbon dioxide carboxylic acids carboxylic acids 2 ' esters 3 o (twice) 3 o (twice) 1 o 2 carboxylic acids acid/base x 1 nucleophile x 1 acid/base acid/base 1 o nitrils N N 2 3 o amides 1 o N 2 1 o,2 o,3 o N 2 l acid chlorides 3 o 3 o 1 o α,β-unsaturated carbonyls 1,2-addition 1,2-addition conjugate addition (1,4-addition) 1,2-addition conjugate addition (1,4-addition) WK = workup with electrophilic/acidic 3 + = applicable to our course (, productive or emphasized) 1,2-addition Z:\classes\315\315 andouts\functional group yn Probs1.doc

13 hem 316 / Beauchamp 13 Use clues in the target molecule to determine what the last step could have been. nce you work back one step, use clues in that molecule to determine how you could work back one additional step. epeat this process until you get to the necessary starting ome points to remember: 1. can be oxidized to aldehydes (from 1 o ) or carboxylic acids (from 1 o, which can be made into esters or acid chlorides and more), or (from 2 o ). 2. can be made into a leaving group (l,, I, Ts), which can be made into amines, esters, nitriles, ethers, alkynes, thiols, thioethers, replaced with /D and much more. 3. can be eliminated in 2 4 /, but rearrangements could be a problem. can be eliminated with potassium t- butoxide, but regioselectivity can be a problem (requires anti β -/ α -X conformation). tarting tructures: 4 3 NaN methyl 3 2 ethyl 3 2 n-propyl n-butyl sec butyl t-butyl 3 3 isopropyl phenyl available until topic 13 TM = butan-1-ol (a few examples) 1. e e = epoxide strategy 2 3 ethyl c c = carbonyl strategy n-propyl 1. B / Na Pd/ 2 1. NaN 2 2. alkyne strategy Pd/ 2 1. NaN alkyne strategy TM = butan-2-ol (a few examples) c c = carbonyl strategy c 3 c = carbonyl strategy 2 e e = epoxide strategy or 1. gx 2 / 2 2. NaB 4 Pd/ 2 1. NaN 2 2. any of these s will work alkyne strategy Z:\classes\315\315 andouts\functional group yn Probs1.doc

14 hem 316 / Beauchamp 14 Alkene s unsubstituted mosubstituted mosubstituted trans disubstituted cis disubstituted cis disubstituted gem disubstituted gem disubstituted trisubstituted tetrasubstituted alkyne patterns 2 4 / & & Ts / &,,, & & (l, I are similar) &,,, rearrangement & & &,,, E & Z Z:\classes\315\315 andouts\functional group yn Probs1.doc

15 hem 316 / Beauchamp g(ac) 2 / 2 2. NaB 4 (avoids rearrangements) N rearrangement & & &,,, 1. g(ac) 2 / 2. NaB (avoids rearrangements) N rearrangement & & E & Z &,,, vniyl ether vniyl ether 1. (B 3 ) 2 diborane 1. 2 B dialkylborane anti-markovnikov addition / for s / for alkynes N rearrangement & &,,,,,, 1. (B 3 ) / 3 diborane for s 1. 2 B 2. 2 / 3 dialkylborane for alkynes anti-markovnikov addition N rearrangement & & E,,,,,, vniyl bromide vniyl bromide Z:\classes\315\315 andouts\functional group yn Probs1.doc

16 hem 316 / Beauchamp 16 2 (l 2 is similar) anti-addition N rearrangement meso (achiral) (dl) or (±) (dl) or (±) & & 2 / 2 (l 2 / 2 is similar) anti-addition / Markovnikov addition an form epoxides with Na N rearrangement meso (achiral) (dl) or (±) (dl) or (±) Pd / 2 palladium & hydrogen syn-addition & & meso Pd / 2 palladium & hydrogen syn-addition Z:\classes\315\315 andouts\functional group yn Probs1.doc

17 hem 316 / Beauchamp 17 Na / N 3 in ammonia anti-addition potassium permanganate syn-addition KMn 4 or s 4 osmium tetroxide & (dl) or (±) meso (achiral) meso (achiral) N rearrangement cis and trans to methyl meso (achiral) l meta chloroperbenzoic acid (mpba) syn-addition & & & & & cis and trans to methyl & 1. 3, -78 o cleaves double bone into two = groups (aldehydes or ) Z:\classes\315\315 andouts\functional group yn Probs1.doc

18 hem 316 / Beauchamp , -78 o 2. NaB 4 cleaves double bone into two alcohol groups , -78 o cleaves double bone into two = groups (acids or ) , I 2 Zn / u immons mith reagent syn-addition & & & & & & cis and trans to methyl 2 I 2 Zn / u immons mith reagent syn-addition X = or l X X X X 2 X 2 2 X 2 & & & & & X X 2 X 2 X 2 & cis and trans to methyl Z:\classes\315\315 andouts\functional group yn Probs1.doc