1. reaction is the transformation of one or more compounds ...



Addition to carbonyl compounds (skip 8.25, Me3SiCN, 8.27, 8.4.5-7, 8.5, 8.7general properties significant CO dipole attracts Lewis acids and baseslone pairs and partial charge at oxygenpolarized ? electrons readily displaced toward oxygenplanar electrophile (3 sp2 hybridized orbitals), easy access addition results in rehybridization (4 sp3 orbitals), brings substituents closer togetherunactivated carbonyl reacts with good nucleophilesRS-, CN-, RLi, RMgBr, RO-, RNH2 Acids activate carbonyl but deactivate basic nucleophileLewis acid required for weak nucleophilesROH, RSH, arene, PhNH2 hydrogen bonding in protic solvent weakly activates Carbonyl is activated by electron withdrawing groups deactivated by electron donating groups, bulky groups, resonancealkyl groups stabilize, and sterically inhibit attack, sp2 to sp3 (see hydration)Hydration – water additionreadily occurs for formaldehyde (reactive carbonyl) but not acetonesteric and electronic effecthydration unfavorable for most ketoneshydration is reversible, 18O slow at pH 7, fast with trace acid or baseoccurs in acid or base condition.RDS is water addition.GA, GB, SA and SB catalysis. What is mechanism with base-catalyzed water addition?Alcohol addition is reversible as well: acetal and ketal formationacetals from aldehydes, ketals from ketonesformation of hemiacetal fast when acid or base catalyzed even if not favorablehemiacetal is half alcohol, half ether from aldehyde, addition half donemechanism just like hydrationprotonation of OH leads to dehydration and to acetalgeminal oxygen assists loss of water by concerted bond making with bond breakingOH is poor leaving group, WHY? protonate firstnote interchange between 3 sp2 and 4 sp3 orbitals, preserves octet acid or base conditions forms hemiacetal, only acid forms the acetal. Why?drive reaction to completion with water or alcohol acetal is base stable, requires proton for loss of OR groupketals normally only form with diolsacetal and ketal formation good for protecting carbonyl from nucleophiles and strong basesthioacetals and thioketals also form, not as readily reversiblecyanohydrinquantitative for aldehydes and ketones but not aromatic ketones:HCN plus catalytic amount of base. show mechanism?CN attack rate determining, rate = k[R2CO][CN-]HCl additionequilibrium poor in water because Cl- is good leaving groupaddition works in alcohol where ether is stable, why?metal hydridesaldehydes and ketone have single H- additionesters have two H- addition, loss of OR has assistance from geminal oxygen and AlX3?LiAlH4 reacts with aldehydes, ketones, esters, carboxylic acids and amidesCannot use protic solvent?NaBH4, reacts with aldehyde and ketones selectively reduce ketone in presence of amide? Amide in presence of ketone?Meerwein-Pondorf – carbon to carbon H transfermetal alkoxide transfer ? H6-member cyclic transition stateAl is important in bringing together alkoxide and carbonylequilibrium determined by reactivity of carbonyldriven by removal of propanone by distillationCannizzaro Reactiondisproportionation, two aldehydes, one oxidized, the other reduced Rate = k[PhCHO]2[HO-] Hydride transfer assisted by geminal oxygendoes not work with ketones, alkyl does not migrateamino group additionacid catalyzed, but not too much, Why?low pH (RDS changes with pH) water elimination is fast (why?)amino group is protonated and amino addition is rate limitinghigh pHwater elimination is slow (why?) and rate limitingamine addition is fasterimine is more stable than enamine but tends to polymerizesecondary amines can only form enamines (why?)enamine is formed like an enolpowerful nucleophiles when R = OH, H, alkyl, NH2, NHCONH2, NHPhi.e. H2NOH, NH3, H2NNH2, etc. Grignard additionchelation by Mg important, impedes acid base reactionacid base reactions compete for carbonyl with ?-Hreaction with esters? What is the product?RLi tend not to undergo acid base reaction, or hydride transfer prefer 1,2 over 1,4 additionR2Cd react with ketones/aldehydes but not estersacetylide additionaldol condensationbase catalyzed – enolate formationcarbonyl activates ?-CH, stabilized anionequilibrium favorable for aldehydesnot favorable for ketonesacid catalyzed – enol formation add protonfavorable for aldehydes and ketonestertiary alcohol products dehydrate, easy formation of tertiary carbocationcrossed aldolmixed aldehydes gives four possible products if both aldehydes have ?-Hsynthetically useful if one does not have ?-HClaisen Condensation add a lone pairunfavorable leaving group assisted by geminal oxygenpKa of ?-keto ester?equilibrium favors ?-keto enolateneutralize to obtain productDieckmann - intramolecular Claisen condensation (in class)Benzoin condensationAromatic aldehydes used to avoid aldol condensationstart with cyanohydrin formationRate = k[ArCHO]2[CN-], rate determining step? nucleophilic catalysisBenzylic acid rearrangementmigration of Ph to electron deficient atom (carbon)similar to rearrangement of carbon cationin PhCOCHO, H instead of Ph migratesWittig reaction: phosphonium ylidePhosphorus like amine, good nucleophile, not as good base (poor overlap)Phosphorus is polarizable, lone pair deformed by electrophileformation of strong P=O bond drives reactiondoes not react with esters or unconjugated C=CAddition/elimination of acid derivatives: X = direct heteroatom attached: halogen, S, O, N?trigonal-tetrahedral interchange, oxygen lone-pair assisted dissociationconcerted SN2 never observedAKA acyl transfer reactions (for example, from X to Y)base “catalyzed” hydrolysis of esters follows this mechanism no attack on R’, no label in carboxylate: Carbonyl 18O shows up in water. How??H* = 112 kJ mol-1, ?S* = -109 J K-1 mol-1OH-, OR-, RNH2 attack ester carbonyl without acid catalysisacid catalyzed hydrolysis: 18O in carbonyl, 30 min recover all starting material, missing some 18O, is in the water??H* = 75 kJ mol-1, ?S* = -105 J K-1 mol-1normally O-acyl not O-ether cleavageIf R’ makes good carbon cation (tert-butyl or benzyl) carboyxlate leaves and ether oxygen cleavesFor t-butyl ester: ?H* = 112 kJ mol-1, ?S* = 55 J K-1 mol-1if acyl group is bulky, acylium is formed (strongly ionizing solvent required?)acid esterification, same mechanism and restrictionsacid hydrolysis activation parameters indicate two different mechanisms ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download