Prelim Exam 3: Carboxylic Acids and Derivatives; Carbonyl Alpha Substitution Reactions; Carbonyl Condensation Reactions; Amines (Chem 322 - Organic Chemistry) Flashcards
acid halide (RCOX) nomenclature
identify first acyl group then halide… suffix “oyl” (or “carbonyl” for cyclic acid halides)… “alkanoyl halide” or “cycloalkanecarbonyl halide”
acid anhydrides (RCO2COR’) nomenclature
symmetrical anhydrides of unsubstituted monocarboxylic acids and cyclic anhydrides of dicarboxylic acids are named with ending “anhydride”… unsymmetrical anhydrides are named by listing two acids alphabetically then adding “anhydride”… “alkanoic anhydride” or “alkanoic alkanoic anhydride”
esters (RCO2R’) nomenclature
identify alkyl group attached to oxygen and then carboxylic acid with “ate” suffix… “alkyl alkanoate”
amides (RCONH2) nomenclature
“amide” suffix or “carboxamide” suffix (for cyclic compounds)… if nitrogen atom is further substituted, compound is named by identifying substituent groups then parent amide: substituents are preceded by letter “N” to identify them as being attached to nitrogen… “alkanamide” or “cycloalkanecarboxamide” or “N-alkylalkanamide”
thioesters (RCOSR’) nomenclature
prefix “thio” if a common related ester name… suffix “thioate” or “carbothioate”… “alkyl alkanethioate” or “alkyl cycloalkanecarbothioate”
acyl phosphates (RCO2PO3 2- and RCO2PO3R’-) nomenclature
cite the acyl groups and add the word “phosphate”… “alkoyl phosphate”
nucleophilic acyl substitution reactions
net effect: substitution of nucleophile for -Y group originally bonded to acyl carbon… takes place in two steps and involves a tetrahedral intermediate
relative reactivity of carboxylic acid derivatives
sterically, unhindered/accessible carbonyl groups react with nucleophiles more readily than do sterically hindered groups… electronically, strongly polarized acyl compounds react more readily than less polar ones
nomenclature of amides with competing substituents
alphabetize substituents… di, tri, tetra if more than one substituent… N-substituents come before numerical-substituents
conversion of carboxylic acids into acid chlorides
nucleophilic acyl substitution using SOCl2
conversion of carboxylic acids into acid anhydrides
using heat
conversion of carboxylic acids into esters
SN2 reaction of carboxylate anion with primary alkyl halides
Fischer esterification reaction
acid-catalyzed (strong acid like HCl) nucleophilic acyl substitution reaction of a carboxylic acid with alcohol
conversion of carboxylic acids into amides
use DCC (dicyclohexylcarbodimide)
conversion of carboxylic acid into alcohols
using 1) LiAlH4 / 2) H3O+ or 1) BH3, THF / 2) H3O+
preparation of acid halides
conversion of a carboxylic acid using SOCl2
acyl substitution – basic conditions
using NaOEt, HOEt… occurs through addition and elimination
acyl substitution – acidic conditions
(Fischer esterification reaction) using H3O+… occurs through protonation -> addition -> deprotonation -> protonation -> elimination -> deprotonation
preparation of acid anhydrides
nucleophilic acyl substitution reaction of acid chloride with carboxylate anion
conversion of an acid chloride into an carboxylic acid
hydrolysis – using H2O
conversion of an acid chloride into an acid anhydride
using R’CO2-
conversion of an acid chloride into an ester
alcoholysis… using R’OH
conversion of an acid chloride into an amide
aminolysis… using NH3
conversion of an acid chloride into a ketone
reduction/grignard reaction… using R’2CuLi
conversion of an acid anhydride into a carboxylic acid
hydrolysis… using H2O
conversion of an acid anhydride into an ester
alcoholysis… using R’OH
conversion of an acid anhydride into an amide
aminolysis… using NH3
conversion of an acid anhydride into an alcohol
reduction… one round [H-] yields aldehyde, two rounds [H-] yields alcohol
lactone
cyclic ester
preparation of esters
carboxylic acid + 1) SOCl2 / 2) R’OH… carboxylic acid + R’OH, HCl… carboxylic acid + 1) NaOH / 2) RX
conversion of an ester into an alcohol and carboxylic acid
hydrolysis… using H2O, NaOH, or H3O+
saponification
conversion of an ester into an alcohol and carboxylic acid in basic conditions… uses H2O, NaOH
conversion of an ester into an amide and an alcohol
aminolysis… using NH3
conversion of an ester into an aldehyde and an alcohol
reduction… using 1) DIBAH / 2) H3O+
conversion of an ester into primary alcohols
reduction… using 1) LiAlH4 / 2) H3O+
conversion of an ester into a tertiary alcohol
grignard reaction… using 1) 2 R’MgBr / 2) H3O+
preparation of amides
acid chloride + NH3… acid chloride + R’NH2… acid chloride + R’2NH
lactam
cyclic amide
conversion of an amide into a carboxylic acid + H3O+ + NH3
hydrolysis… using H3O+
conversion of an amide into an amine
reduction… using 1) LiAlH4 / 2) H2O
primary amine
R-NH2
secondary amine
R2 - NH
tertiary amine
R3 - N
quaternary ammonium salt
R4N+ X-
acid chloride + 1) 2 RMgX / 2) H3O+
yields a tertiary alcohol with two identical substituents
most reactive acid derivative
acid chloride
least reactive acid derivative
amides/nitriles
acid chloride + 1) R2CuLi / 2) H3O+
yields a ketone
least reactive carbon nucleophile
cuprates
most reactive carbon nucleophile
grignards
nitrile + 1) RMgX / 2) H3O+
yields a ketone
thiol/thioester reactions
thiol formed by phosphoric anhydride linkage (O=P-O-P=O)… partial reduction of thioester using a hydride ion to form an aldehyde
chain growth polymer
produced in a chain-reaction process where an initiator adds to a C=C bond to give a reactive intermediate, which adds to a second alkene molecule to produce a new intermediate, which adds to a third molecule, and so on
step-growth polymer
each bond in a polymer is independently formed in a discrete step (often by nucleophilic acyl substitution of a carboxylic acid derivative)
polyamides (nylons)
step-growth polymer… heat a diamine with a diacid… nylon #__ (first number is the number of carbons in a diamine, second number is the number of carbons in diacid)
polyesters
step-growth polymer… diester and dialcohol
sutures and biodegradable polymers
common biodegradable polymers: poly(glycolic acid) [PGA], poly(lactic acid) [PLA], poly(hydroxybutyrate) [PHB]
transesterification
The process that transforms one ester to another when an alcohol acts as a nucleophile and displaces the alkoxy group on an ester… using HOR’’, H+
infrared spectroscopy of carboxylic acid derivatives
intense IR absorptions in 1650 - 1850 cm^-1… acid chlorides have absorption near 1810 cm^-1… acid anhydrides have absorptions at 1820 cm^-1 and 1760 cm^-1… esters have absorption at 1735 cm^-1
nuclear magnetic resonance spectroscopy of carboxylic acid derivatives
H’s near carbonyl group absorb near 2 delta in H NMR… but cannot identify the type of carbonyl group
SOCl2
conversion of carboxylic acid into acid chloride
alkyl halide, Sn2 reaction
conversion of carboxylic acid into ester
R’OH, acid catalyst
conversion of carboxylic acid into ester + H2O
RNH2, DCC
conversion of carboxylic acid into an amide
carboxylic acid + 1) LiAlH4 / 2) H3O+
yields a primary alcohol
acid chloride + H2O
hydrolysis to yield a carboxylic acid and HCl
acid chloride + carboxylate (RCO2-)
yields anhydride + Cl-
acid chloride + R’OH, pyridine
yields ester and HCl
acid chloride + 2 NH3
yields amine and NH4Cl
acid chloride + 1) LiAlH4 / 2) H3O+
yields a primary alcohol
acid chloride + R2CuLi
yields a ketone
acid anhydride + H2O
yields 2 carboxylic acids
acid anhydride + ROH
yields ester and carboxylic acid
acid anhydride + 2 NH3
yields an amide and a quaternary ammonium salt
ester + H3O+ or NaOH or H2O
yields a carboxylic acid and an alcohol
ester + 1) LiAlH4 / 2) H3O+
yields two primary alcohols
ester + 1) DIBAH / 2) H3O+
yields an aldehyde and an alcohol
ester + 1) 2 RMgX / 2) H3O+
yields a tertiary alcohol (with two identical substituents) and an alcohol
amide + H3O+ or NaOH or H2O
yields a carboxylic acid + NH3
amide + 1) LiAlH4 / 2) H3O+
yields an amine
n*peptide
possibilities of peptides: n!
[ex: tetrapeptide = 4 x 3 x 2 x 1 = 24 possibilites]
making amines
R-X + NaCN -> R-CN + 1) LiAlH4 / 2) H2O -> R-CH2-NH2…
RCONH2 + 1) LiAlH4 / 2) H2O -> R-CH2-NH2…
RCONHR + 1) LiAlH4 / 2) H2O -> R-CH2-NHR…
RCONR2 + 1) LiAlH4 / 2) H2O -> R-CH2-NR2
α-substitution reaction
occurs at position next to carbonyl group (α position) and involve substitution of a α hydrogen by electrophile through either an enol or enolate intermediate
tautomers
rapidly interconverting isomers differing in a H position or a pi bond position
keto-enol tautomerism
tautomers are constitutional isomers (different compound with different structures)… enol can only predominate when stabilized by conjugation or intramolecular hydrogen bonding… only hydrogens at α position of carbonyl groups are acidic
enols
act as nucleophiles to react with electrophiles; reacts to yield α-substituted carbonyl compound
alpha halogenation of aldehydes/ketones
depends on aldehyde/ketone and acid concentrations…. α-bromo ketones can be dehydrobrominated to yield α, β-unsaturated ketones… deuteration (D3O+) can also slowly occur, where D adds to α
alpha bromination of carboxylic acids
acids/esters/amides cannot enolize to a sufficient extent to undergo alpha bromination… carboxylic acids can be alpha brominated by a mixture of Br2 and PBr3 in Hell-Volhard-Zelinski (HVZ) reaction
pyridine
pulls off the beta hydrogen to produce a α, β-unsaturated carbonyl compound
strong base is needed for enolate ion formation because
carbonyl compounds are weakly acidic
LDA
commonly used for making enolate ions from carbonyl compounds
when a hydrogen atom is between two carbonyl groups
its acidity increases
enolate ions are more useful than enols
stable solutions of pure enolate ions are easily prepared from most carbonyl compounds by reaction with a strong base… enolate ions are more reactive than enols and undergo many reactions that enols do not (because enolate ions are negatively charged, making them better nucleophiles)
haloform reaction
*when a base is used with a methyl ketone, the alpha carbon will become completely halogenated.
*this trihalo product reacts further with the base to produce a carboxylic acid and a haloform (CHX3)
forming alkenes through Sn2 using primary alcohol
convert to a primary alkyl halide, then use a bulky base (NaOt-butyl)
forming alkenes through E1 using secondary or tertiary alcohol
use H2SO4, H2O