ucleophilic ubstitution & Elimination Chemistry Beauchamp 1 Available chemicals from the catalog (the starting sources of carbon compounds will continually decrease as we learn new reactions. ources of carbon - you can invoke these whenever needed: C 4 ources of carbon - you can until we cover reactions that will make them from the above compounds, then they will go away: Commercially available chemicals and reagents - you can invoke these whenever you need them. 2 Cl Cl 2 I 2 4 3 P 4 3 2 3 2 2 bromine chlorine hydrogen hydrogen hydrogen sulfuric phosphoric nitric acid water ammonia hydrogen chloride bromide iodide acid acid peroxide alts / ionic substances hydride 2 C =Cor azide K amide (excellent nucleophile) nitrite hydroxide cyanide C 2 n-butyl lithium (very strong base or nucleophile, use anytime) hydrogen sulfide diisopropylamine Cl 1. g(ac) 2 / 2. B 4 dithiane meta chloroperbenzoic acid (mcpba) 1. g(ac) 2 / 2 2. B 4 Various s Mg magnesium lithium TP (protect -) 3 C methyl lithium Ph potassium hydride 2 C phenyl lithium B = -bromosuccinimide (supplies free radical bromine for allylic & benzylic substitution) Ph pre aldehydes/ketones P Ph triphenylphosphine (to make Wittig salts) / 3 in ammonia (Birch reagent) CCl 3 chloroform C 3 bromoform Zn zinc Pd / 2 palladium & hydrogen B borohydride (nucleophylic hydride) phthalimide (an imide) C 2 I 2 Zn / Cu immons mith reagent Pd / 2 quinoline (ndlar's cat) toluene sulfonic acid = Ts (very strong organic acid) ethanoic acid a carboxylic acid) pre alds / kets Cr 3ozone reactions pyridine 1. 3,-78 o (PCC) C 2. C 3 C 3 1. 3,-78 o C 2. B 4 1. 3,-78 o C 2. 2 2, gx 2 (mecuric salts) Al lithium aluminumhydride = LA (very strong nucleophilic hydride) (AlD 4 too) ketone (a carbonyl) pre alds / kets C 2 carbon dioxide Mn Cr 2 / 3 + (Jones) diborane diborane use w/ alkenes use w/ alkenes 1. B 1. B 2. 2 2 / 2. 2 /C 3 Cl I K potassium permanganate osmium tetroxide 2 2 ethylene hydrazine pyrrolidine glycol (Wolff-Kishner) (enamines) (protect C=) Cl = Ts-Cl (tosyl chloride) makes into tosylates t-butyl alcohol (use to make t-butoxide) s Cu cuprous bromide B C cyanoborohydride (nucleophylic hydride) (BD 4 too) = py pyridine = proton sponge dialkylborane use w/ alkynes 1. B 2. 2 2 / Lewis acids Al 3 Fe 3 BF 3 Cl 2 P 3 3 etc. Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc
ucleophilic ubstitution & Elimination Chemistry Beauchamp 2 C1 through C7 - examples (no stereochemistry indicated; enantiomers and diastereomers). oon any of these will be within our grasp ( and more). 1C 2C 3C 4C 3 C 5C 6C 6C 6C Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc
ucleophilic ubstitution & Elimination Chemistry Beauchamp 3 Group A (bromo compounds from free radical substitution at sp 3 C- positions, from alcohols and alkenes) make various ways 3 C given until alkenes Group C ( from methyl and primary bromides and hydroxide via 2 reactions; from secondary and tertiary bromides and water via 1, but rearrangements are possible; also from alkenes, carbonyls and epoxides) make various ways 3 C Group D (esters from methyl, primary and secondary bromides and carboxylates (acetate, here) via 2 reactions, esters can be hydrolyzed to alcohols via acyl substitution with hydroxide, and via 1 at tertiary X and various other methods we will learn) Group F (ethers from methyl and primary bromides and alkoxides via 2 reactions, t-butoxide reacts mostly by E2, 2 o X and 3 o X mainly form E2 products too) (ethers from secondary and tertiary bromides and alcohols via 1, but rearrangements are possible) Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc
ucleophilic ubstitution & Elimination Chemistry Beauchamp 4 Epoxides are special ethers that can be made from bromohydrins + base or alkenes + mcpba (later). The large ring strain allows them to be easily opened by strong nucleophile/bases or in strong acid. Group G (amines from methyl, primary and secondary bromides and conjugate base of phthalimide via 2 reactions, the alkyl imide can be hydrolyzed to primary amines via two acyl substitutions with hydroxide, see mechanism above) or make azides via 2 reactions and then react using 1. Al 4, 2. workup. Group (tosylates formed from alcohols and tosyl chloride/pyridine via acyl substitution reaction, converts from poor leaving group into a very good leaving group similar to iodide) 3 C Ts Ts Ts Ts Ts Ts Ts Ts Ts Ts Ts Ts Group I (alkenes formed by E2 reaction with potassium t-butoxide and - compounds or make via E1 reactions of and 2 4 / ) Group J (make ethyne or propyne using dibromo ethane or propane and double E2 reactions using 2 ), ( make other alkynes from terminal acetylide and methyl or primary X via 2 reaction; two reactions are possible in stepwise manner on both sides of ethyne, can put one or two groups on, mostly E2 reaction at 2 o - and only E2 at 3 o X), can use zipper reaction to move alkyne to end position along unsubstituted linear chain and start over. Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc
ucleophilic ubstitution & Elimination Chemistry Beauchamp 5 Group K (nitriles from cyanide and methyl, primary and secondary X via 2 reaction, reaction, only E2 reaction at 3 o -; or make from primary amides + Cl 2 ) Group L (thiols from hydrogen sulfide and methyl, primary and secondary X via 2 reaction, reaction, only E2 reaction at 3 o - in our course), Can do reaction a second time and make sulfides, 1 -- 2. 3 C 3 C Group M (synthesis of ketones from 2-propanone (acetone) via 2 with propanone enolate at methyl, 1 o, 2 o X. nly E1 at 3 o X. Make propanone enolate from propanone and lithium diisopropylamide = LDA at 78 o C, made from diisopropylamine and n-butyl lithium shown on page 2 under useful acid/base reactions.) Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc
ucleophilic ubstitution & Elimination Chemistry Beauchamp 6 Group (synthesis of esters from ethyl ethanoate (ethyl acetate) via 2 using an ester enolate at methyl, 1 o, 2 o X. nly E1 at 3 o X. Make ester enolate from ester and lithium diisopropylamide = LDA at 78 o C, made from diisopropylamine and n-butyl lithium shown on page 2 under useful acid/base reactions.) LDA = lithium diisopropylamide ethyl ethanoate ethyl acetate 1 acid/base rxn -78 o C carbanion nucleophile 2 rxn X new bond These are examples there are other possibilities. Make carbonyl compounds from alcohols (aldehydes (PCC), ketones (PCC or Jones) and carboxylic acids (Jones). There are many other methods too. aldehydes carboxylic acids (remember these can be made into esters) ketones Make acid chlorides from carboxylic acids + thionyl chloride (Cl 2 ). Acid chlorides can be made into many things including esters, amides and anhydrides (for now). Z:\files\classes\315\315 andouts\available chemicals, syn targets & chem catalog.doc