Unit 3 Orgo Chem Lecture 1

Carboxylic Acid derivatives

Acyl substitution

reactivity corresponds with

reactivity of conjugate acid of leaving group

ex. acid chloride is most reactive, HCl con acid is very acidic

nucleophilic addition is

RLS

same factors that determine electrophilicity determine acidity

reactivity order

acid chloride > acid anhydride > ester > amide

making an acid chloride from carboxylic acid

react with SOCl2

turning carb acid into acid chloride

Vilsmier reagent

Making an acid chloride using vilsmeier reagent

DMF was catalyst! regenerated

making the vilsmier reagent

Fisher esterification:

carboxylic acid → ester via acid catalyst

Example fisher esterification

weak nucleophile attacks

OH made good LG via protonation

need excess of one reagent

other rxn to make an ester from carb acid

making amides from carboxylic acids

use a carbodiamide

mechanism of amide creation with carb acid

Peptide synthesis

must protect the RHN and OR groups first!

strings peptides together

tBOC of fBOC

protects the RHN and RO in

deprotecting

remove tBOC or fBOC

remove tBOC with CF-C=O-OH

fMOC removed with piperidine

carboxylic acids to alcohol

use LiAlH4 with H+ or BH3, THF with H3O+

example with LiAlH4

if you want a nitrile group to remain intact

use BH3, THF H3O+, LiAlH4 will reduce everything!

it’s a more selective, milder reagent

making a carb acid from acid chloride

making an alcohol from an acid chloride

reducing acid chlorides with LiAlH4

with girngard reagent

Acid chloride reaction with gilman