Relative Reactivity of Acid Derivatives

addn elim can occur…

with either strong nu under basic or weak nu under acidic

strong nu

grignard, organolithium, acetylide, hydride

strong nu what is not reverisble

addn

for strong nu rate is dependent on

addn (addn fav usually cuz strong nu more basic than alkoxide)

most reactive derivativie has fastest addn

rate of rxn

for addn and elimation (best lg)

fastest acid chloride, anhydride, esther, amides, carboxylate (coo- cant do elim) slowest

weak nu

water and alcohol

weak nu rate dependent

on elim

derivativie with best lg has fastest elim

rate of elim

cl- and coo- good leaving group sof acid chloride an dnahydride

o-r can leave need some other step to make it go
h2n-r slow rate of elim cuz more basic than alcohol

hydrolysis

is weird cuz not strong nu but acid chlorides and anhydrides dont need acid catalyst

ester and amide shave lgs that have similar or lessa cidic than intermediate

unsure whether addn or ellim is favorable and mkaes rxns go

hydrolysis of acid chloride

very readily do hydrolysis to cooh

H2O and weak base like na2co3 to make cooh

weak base neutral strong acids so hydrolysis can be just h2o

can also hydrolyze in more basic conditions h2o/oh-

carboxylate is formed

carboxylate formation can help drive the rxn

hydrolysis of anhydride

works with just water also works with acid cat in water to cooh

also work under basic h2o/oh-

carboxylate is formed

carboxylate formation can help drive the rxn

what about hydrolysis of cocl and anhydrides?

addn of water to them occur w/o acitvation

addn is fast, not necesssarily favorable

elim is fav for both derivatives under basic conditions

elim more complex for anhydrides under neutral or acidic conditions

hydrolysis of ester (acidic)

can hydrolyze in acid and water to cooh

reverse of fischer esterification

no inherent DF

use le chatelier’s principle to help drive rxn

what about hydrolysis of ester (acidic)

addn of water to esters required activated c=o

addn is neither fav or unfav as water is about as basic as the alcohol int

for esters lg is an alcohol and elim is neither fav or unfav

NEED TO CREATE DF

hydrolysis of ester (basic)

saponification with h2o/ho- to coo-

hydrolysis under basic condiiotns

carboxylate is formed, formation drives rxn

what about hydrolysis of ester (basic)

addn of hydroxide from an alkoxide (tetrahedral int)

hydroxide and alkoxides are comparalbe bascity addn is neither fav or unfav

lg is an alkoxide and elim is neihter fav or unfav

must be a step after elim that helps drive rxn (deprotonation)

hydrolysis of amides (acidic)

readily under acidic aq conditions cooh

DF is formation of ammonium

what about hydrolysis of amides (acidic)

addn of water need acitvated c=o

addn is neither fav or unfav cuz alcohol int as basic and water

amides the lg is an amine and elim is NOT fav

step after elim to help drive, nh4+ is weaker acid than hydronium

hydrolysis of amides (basic)

h2o/ho-

rxn so slow unlikely to occur need high pressure and heat

rxn basically does not occur

what about hydrolysis of amides (basic)

addn of hydroxide forms alkoxide int

hydoxrides and alkoxides sim basciity addn neither fav or unfav

elim is VERY slow an dunfav cuz LG nitorgen anion is a strong base

hydrolysis of nitriles (acidic)

h+/h2o turn into cooh

addn of water to nitrile is like addn to activated c=o

nitrile goes thru an amid eint during hydrolysis

hydrolysis continues to carboxylic acid via the same process as amide hydrloysis

hydrolysis of nitrile (basic)

with h2o/ho- STOP at amide cuz amide hydrolysis is not fav under basic cond

addn of hydorxide to nitrile is not favorable

addn follwoed with a favorable acid base step