203 Genera| Mechan|sm for Nuc|eoph|||c Acy| Subst|tut|on

Nocleopblllc Acyl 5obstltotloo

8eacLlon ls feaslble when a less sLablllzed carbonyl ls converLed Lo a more sLablllzed one (more reacLlve Lo less reacLlve)


Ceoetol Mecboolsm fot Nocleopblllc Acyl 5obstltotloo
lnvolves formaLlon and dlssoclaLlon of a LeLrahedral lnLermedlaLe
8oLh sLages can lnvolve several elemenLary sLeps
flrsL sLage of mechanlsm (formaLlon of LeLrahedral lnLermedlaLe) ls analogous Lo nucleophlllc addlLlon Lo CC of aldehydes and
keLones

second sLage ls resLoraLlon of CC by ellmlnaLlon
compllcaLlng feaLures of each sLage lnvolve acldbase chemlsLry
Acldbase chemlsLry ln flrsL sLage ls famlllar ln LhaL lL has Lo do wlLh acld/base caLalysls of nucleophlllc addlLlon Lo CC
Acldbase chemlsLry ln second sLage concerns form ln whlch Lhe LeLrahedral lnLermedlaLe exlsLs under Lhe reacLlon condlLlons
and how lL dlssoclaLes under Lhose condlLlons


1be 1ettobeJtol lotetmeJlote
LeLrahedral lnLermedlaLe (1l)




lssoclotloo of 1ln-



lssoclotloo of 1l



lssoclotloo of 1l



204 Nuc|eoph|||c Subst|tut|on |n Acy| Ch|or|des


9tepototloo of Acyl cblotlJes
from carboxyllc aclds and Lhlonyl chlorlde (SecLlon 127)

eoctloos of Acyl cblotlJes
Acyl chlorldes reacL wlLh carboxyllc aclds Lo glve acld anhydrldes

xomple

eoctloos of Acyl cblotlJes Acyl chlorldes reacL wlLh alcohols Lo glve esLers

xomple

eoctloos of Acyl cblotlJes Acyl chlorldes reacL wlLh ammonla and amlnes Lo glve amldes


xomple

eoctloos of Acyl cblotlJes Acyl cblotlJes teoct wltb wotet to qlve cotboxyllc oclJs (cotboxylote loo lo bose)

Acyl chlorldes reacL wlLh waLer Lo glve carboxyllc aclds (carboxylaLe lon ln base)

xomple



eoctlvlty
Acyl chlorldes undergo nucleophlllc subsLlLuLlon much fasLer Lhan alkyl chlorldes



203 nucleophlllc Acyl SubsLlLuLlon ln Carboxyllc Acld Anhydrldes
Anhydrldes can be prepared from acyl chlorldes as descrlbed ln 1able 201


5ome oobyJtlJes ote loJosttlol cbemlcols

tom Jlcotboxyllc oclJs
Cycllc anhydrldes wlLh 3 and 6membered rlngs can be prepared by dehydraLlon of dlcarboxyllc aclds



eoctloos of AobyJtlJes



eoctloos of AclJ AobyJtlJes
Carboxyllc acld anhydrldes reacL wlLh alcohols Lo glve esLers

normally symmeLrlcal anhydrldes are used (boLh 8 groups Lhe same) reacLlon can be carrled ouL ln presence of pyrldlne (a base)
or lL can be caLalyzed by aclds


eoctloos of AclJ AobyJtlJes
Carboxyllc acld anhydrldes reacL wlLh alcohols Lo glve esLers

xomple



eoctloos of AclJ AobyJtlJes
Acld anhydrldes reacL wlLh ammonla and amlnes Lo glve amldes