Chem%345%Extraneous%Information:% The$procedure$in$the$box$came$from%Modern'Organic'Synthesis'in'the'Laboratory$by$ Jie$Jack$Li,$Chris$Limberakis,$and$Derek$Pflum.$$This$book$contains$some$examples$of$ common$procedures$used$in$the$laboratory.$$They$combed$the$literature$to$find$ procedures$for$reactions/techniques$and$then$published$a$book.$$Do$you$need$to$ know$this$for$Chem$345?$$Well,$not$at$all.$$I$thought$that$some$of$you$might$like$to$ see$how$chemists$actually$carry$out$these$syntheses.$$It$may$be$helpful$for$those$ enrolled$in$Chem$344.$$If$you$go$into$graduate$school$for$organic$chemistry,$then$I$ highly$suggest$that$you$get$the$book,$but$not$before.$$This$particular$procedure$for$ acetal$formation$comes$from$J.'Org.'Chem.'2004,%69,$6751K6760.$ $ $

O HO OH

O O PPTS, PhH, reflux overnight 48% ynone $ To$a$solution$of$ynone$(3.8$g,$28.3$mmol)$in$benzene$(70$mL)$was$added$PPTS$(0.7$ g,$2.83$mmol)$and$2,2KdimethylK1,3Kpropane$diol$(2.95$g,$28.3$mmol),$and$the$ resulting$solution$was$refluxed$overnight$under$DeanKStark$conditions.$$The$ reaction$was$cooled$to$room$temperature$and$quenched$with$saturated$NaHCO3$ solution.$$The$product$was$extracted$with$CH2Cl2$and$the$organic$layer$dried$over$ MgSO4$and$the$solvent$was$evaporated.$$Purification$of$the$residue$by$flash$ chromatography$(hexane/CH2Cl2$10:1$to$4:1)$furnished$the$acetal$(2.5$g,$48%).$ $ Interpretation:$$$ $ Some$names$are$so$unwieldy,$that$often$chemists$will$abbreviate$it$by$a$key$ feature.$$In$this$case,$ynone$is$used.$$Yn$refers$to$an$alkyne.$$One$refers$to$the$ketone.$$ So$a$molecule$containing$an$alkyne$and$a$ ketone$is$an$ynone.$$PPTS$is$short$for$ H pyridinnium$pKtoluenesulfonate.$$PPTS$is$a$ N O very$mild$acid$(pKa~5)$that$is$soluble$in$a$ S wide$range$of$organic$solvents$unlike$sulfuric$ O acid,$which$is$insoluble$in$benzene$and$is$a$ O very$strong$acid$(pKa~K3).$ PPTS PhH$is$a$shorthand$abbreviation$for$ benzene.$$Benzene$is$a$solvent.$$Benzene$is$used$in$this$context$as$it$unreactive$ under$these$conditions$and$is$not$miscible$with$water.$$Since$water$and$benzene$do$ not$mix,$it$is$possible$to$separate$water$from$benzene.$$A$useful$tool$for$this$is$a$ DeanKStark$trap.$$It$is$a$special$piece$of$glassware$that$removes$water$so$long$as$an$ organic$solvent$is$present$that$is$immiscible$with$water.$$We’ll$have$a$DeanKStark$ trap$demo$in$lecture$in$a$couple$of$weeks.$$$ Reflux$is$a$glassware$setup$where$you$boil$the$contents$of$a$flask$and$the$ solvent$evaporates.$$The$solvent$vapor$goes$up$a$tube$that$is$cooled$and$ recondenses.$$The$condensate$then$drips$back$into$the$reaction.$$Reflux$provides$a$ way$to$continually$boil$a$reaction$but$not$lose$solvent.$$The$temperature$that$a$ reaction$mixture$is$heated$depends$on$the$boiling$point$of$the$solvent.$$In$this$case$ benzene$has$a$boiling$point$of$$80°C,$so$the$reaction$does$not$get$much$hotter$than$ 80°C.$$$ The$workup$(isolation$of$product)$comes$next.$$Since$acetal$reactions$are$acid$ catalyzed$equilibrium$reactions,$it$is$important$to$kill$off$the$acid$catalyst$before$any$ water$is$added$and$the$reaction$goes$backwards.$$Saturated$NaHCO3$is$merely$ baking$soda$dissolved$in$water,$and$it$is$a$mild$based$used$to$destroy$any$acid.$$It$ reacts$with$acids$to$form$water$and$carbon$dioxide.$$It$is$now$necessary$to$remove$ water$soluble$impurities$from$the$organic$product.$$Dichloromethane$(CH2Cl2)$is$ often$used$as$it$is$cheap,$volatile,$and$is$not$miscible$with$water.$$The$product$and$ ynone$are$soluble$in$dichloromethane$while$the$PPTS$and$NaHCO3$is$not.$$As$a$ result,$the$product,$benzene$and$any$remaining$ynone$go$into$the$dichloromethane$ while$the$PPTS,$NaHCO3,$and$probably$a$little$of$the$remaining$diol$go$into$the$ water.$$Since$dichloromethane$and$water$do$not$mix,$you$can$separate$the$two$using$ a$piece$of$glassware$called$a$separation$funnel.$$(You$will$use$this$a$lot$in$Chem$344).$$$ Water$is$slightly$soluble$in$dichloromethane$so$MgSO4$is$added$to$scavenge$ any$remaining$water$molecules.$$MgSO4$is$not$soluble$in$dichloromethane$so$it$and$ any$trapped$water$are$filtered$away.$$The$dichloromethane$is$then$removed$from$ the$product$by$simple$evaporation.$$Dichloromethane$has$a$boiling$point$of$40°C$so$ it$is$easily$removed$and$the$benzene$goes$with$it$leaving$the$product$that$is$ contaminated$with$a$little$bit$of$ynone$and$a$little$bit$of$diol.$$The$way$to$separate$ these$is$by$flash$chromatography.$$This$procedure$separates$molecules$based$on$ polarity$to$give$the$product.$$The$yield$of$this$reaction$is$48%.$$It$is$important$to$ note$that$reactions$do$not$always$yield$100%.$$It$is$just$a$fact$of$life.$$Side$reactions$ or$slow$reactivity$or$loss$during$extraction$or$chromatography$steps$are$all$quite$ common.$$