CHEM 233 Lab 10 Study Questions PDF

Preview

Summary

Lecture reading from TA...

Description

CHEM%233%–%Lab%10%Study%Questions! ! pp.!115&116:!Questions!in!black.!!Answers!in!blue.! ! 1)!Looking!at!each!reagent!used!during!the!synthesis!and!work&up,!decide!if!the!following!substitutions! could!be!made,!and!note!why!or!why!not!they!are!appropriate:! a) Sodium!hydroxide!for!potassium!carbonate! b) Propanol!for!2&butanone! c) Ether!for!ethyl!acetate! d) Water!for!5%!NaOH!(aq)! ! a) Sodium!hydroxide!for!potassium!carbonate!is!an!appropriate!substitution.!!Potassium!carbonate! is!used!to!deprotonate!the!alcohol!in!the!first!step!of!the!Williamson!ether!synthesis,!and!since! NaOH!is!a!stronger!base!than!K2CO3,!the!substitution!will!allow!the!reaction!to!proceed.! b) Propanol!for!2&butanone!is! not!an!appropriate!substitution.!!2&Butanone!is!the!solvent,!and!since! the! second! step! of! the! W.E.! synthesis! is! an! SN2! reaction,! the! best! solvents! to! use! are! polar,! aprotic!solvents.!!Protic!solvents,!such!as!propanol,!hydrogen!bond!and!solvate!the!nucleophile,! which!hinders!its!approach!on!the!electrophile.!!Note:% It’s!not!impossible!to!use!propanol!for!this! reaction,!but!it’s!not!an!upgrade!on!2&butanone,!which!is!aprotic.! c) Ether!for! ethyl!acetate! is!an! appropriate!substitution.!! Ethyl!acetate! is!used! to!wash! the!solids! from! the! reaction! in! order! to! maximize! the! amount! of! organic! product! in! the! filtrate,! and! is! immiscible!with!water,!which!is!used!in!the!next!step!for!the!extraction.!!Since!ether!is!organic! and!immiscible!with!water,!the!substitution!is!appropriate.! d) Water!for!5%!NaOH!is!not!an!appropriate!substitution.!!Sodium!hydroxide!is!used!to!deprotonate! any! unreacted! acetaminophen,! thus! making! it! ionic! and! more! soluble! in! the! aqueous! layer.! ! If! just! water! is! used! then! the! acetaminophen! will! remain! in! the! organic! phases! and! will! not! be! removed!for!the!product!phenacetin!(i.e.!phenacetin!will!not!be!purified).s! ! 2)! Why!does!phenacetin!remain!in!the!organic!layer!during!work&up,!but!acetaminophen!is!extracted!to! the!aqueous!layer?! ! See!d)!above.!!Acetaminophen!has!a!phenol,!which!can!be!deprotonated!by!a!base!(recall!from!lab!6!that! there! are! 3! functional! groups! that! can! be! modified! by! acid! or! base! during! an! extraction! –! carboxylic! acids,! phenols,! and! amines).! ! Once! the! phenol! is! deprotonated! the! oxygen! is! negatively! charged,! and! therefore!the!ionized!acetaminophen!is!more!soluble!in!water!than!it!is!in!organic!solvents.!!! ! H N

H N +

O O

H

Na + OH

+ -

O O

H 2O

Na +

! ! Phenacetin,!on!the!other!hand,!has!no!functional!group!that!can!be!deprotonated!by!sodium!hydroxide,! and!therefore!it!will!remain!in!the!organic!layer!during!the!extraction.!!! ! !

3)! If! we! tried! the! same! reaction! with! iodoethane! and! potassium! carbonate,! but! instead! used! cyclohexanol!as!the!alcohol,!would!the!reaction!still!proceed!as!expected?!!If!not,!explain!why.! ! No,!the!reaction!would! not!proceed!as!expected.!!Alcohols!are!not!very!acidic,!and!cyclohexanol!has!a! pKa!of!~!16.!!For!an!effective!deprotonation,!the!equilibrium!of!the!acid/base!reaction!should!lie!toward! the!right! (i.e.!Keq!>>!1).!!Recall!from!lab!6!that! Keq!=!10&{pKa!(left!acid)! –!pKa!(right!acid)],!so!for!this!reaction!with! cyclohexanol! and! potassium! carbonate,! Keq! is! much! less! than! 1,! which! means! that! very! little! cyclohexanol!is!deprotonated.! !

O

H

+

O K+

K 2CO3

+

KHCO 3 pK a = 10.32

pK a = 16 K eq = 10 -(16-10.32) = 10 -5.68 = 2.09 x 10 -6

! Alcohols! themselves!are! not!sufficiently! nucleophilic! for!the! Williamson!Ether! synthesis! to!occur,! so!if! cyclohexanol!is!not!deporotnated!then!no!appreciable!amount!of!ether!will!be!formed.! ! 4)! If!we!tried!the!same!reaction!with!acetaminophen!and!potassium!carbonate,!but!instead!used! t&butyl! iodide!as!the!alkyl!halide,!would!the!reaction!still!proceed!as!expected?!!If!not,!explain!why.! ! No,!the!reaction!would!not!proceed!as!expected.!!!Williamson!Ether!syntheses!are!subject!to!the!same! limitations! as! SN2! reactions,! one! of! which! is! that! there! is! competition! between! substitution! and! elimination.! ! Tertiary! alcohol! halides,! in! the! presence! of! strong! bases! such! as! alkoxides,! will! undergo! elimination!instead!of!substitution!to!reform!acetaminophen!and!an!alkene!as!the!product!instead!of!the! desired!ether:! ! H

H N + -

O O

! ! ! ! ! ! ! ! ! ! !

H N

CH 2 I

CH 3 CH 3

CH 2

+ O O

H

H 3C

CH3

5)!What!are!the!best!starting!materials!to!use!to!generate!the!following!ethers:! ! O O

O

O

!!!!!!a)!! !!!b)!! !!c)!! !d)!! ! ! ! General!requirements!for!the!W.E.!synthesis:! & alcohol!is!sufficiently!acidic!and/or!base!is!sufficiently!basic!to!facilitate!deprotonation! & methyl!halide!>!primary!alkyl!halide!>!secondary!alkyl!halide!>>!tertiary!alkyl!halide!(not!used)! & alkyl!iodides!>!alkyl!bromides!>!alkyl!chlorides!>>!alkyl!fluorides!(not!used)! & polar,!aprotic!solvent! !! O

OH NaOH +

CH 3I

ACN !!!!!!a)! ! ! Phenol!is!a!good!alcohol,!because!it!is!more!acidic!than!an!aliphatic!alcohol!and!so!a!base!such!as!sodium! hydroxide!may!be!used.!!Methyl!iodide!fits! the!criteria!for!the!electrophile,! and!acetonitrile!is!a! polar,! aprotic!solvent.! ! NaH

+ OH

O

I

acetone !!!!!!b)! ! ! Cyclohexanol! is! not! very! acidic,! so! a! strong! base! such! as! NaH! must! be! used.! ! Isobutyl! iodide! fits! the! criteria!for! the! electrophile,!and! acetone!is! a!polar,! aprotic!solvent.! ! Note! that!we! would!not! want!to! switch! the! alcohol! for! the! alkyl! halide.! ! If! the! iodocyclopentane! were! used! instead! we! would! have! a! secondary!alkyl!halide,!which!is!not!ideal!for!the!W.E.!synthesis.! ! I

+

HO

NaH

O

DMF

!!!!!!!c)! ! ! Isopropanol!is!not!very!acidic,!so!a!strong!base!such!as!NaH!must!be!used.!!Iodomethylcyclohexane!fits! the!criteria!for!the!electrophile,!and!dimethyl!formamide!is!a!polar,!aprotic!solvent.!!Note!that!we!would! not!want!to!switch!the!alcohol!for!the!alkyl!halide.!!If!isopropyl!iodide!were!used!instead!we!would!have! a!secondary!alkyl!halide,!which!is!not!ideal!for!the!W.E.!synthesis.! ! NaH OH

+

CH 3I

DMSO

O

!!!!!!!d)! ! ! 1&methylcyclohexan&1&ol!is!not!very!acidic,!so!a!strong!base!such!as!NaH!must!be!used.!!Methyl!iodide! fits! the! criteria! for! the! electrophile,! and! dimethyl! sulfoxide! is! a! polar,! aprotic! solvent.! ! Note! that! we! would! not! want! to! switch! the! alcohol! for! the! alkyl! halide.! ! If! 1&iodo&1&methylcyclohexane! were! used! instead! we! would! have! a! tertiary! alkyl! halide,! which! would! undergo! elimination! instead! of! the! W.E.! synthesis.!...