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Pka of common functional groups

Structure pKa Comment
H2O 15.7
ROOH ~5 Carboxylic Acid
<0

<0

HCl ~ -5 strong acid
~ 10 amine

ROH ~15 alcohol
~10 phenol; resonance stabilization of
conjugate base

~15 no resonance stabilization

RSH ~10 thiol
>20 keto-enolate

Reactions
Diagram Notes
Fischer Esterification

Carboxylic Acid + Alcohol =
Ester (acid catalyst)
Diagram Notes
Imide Hydrolysis followed by
Amide hydrolysis

Phtalimide amination

Cyanate Reactions
-Reduction to amine
-hydrolysis to carboxylic acid
Diagram Notes
triglyceride synthesis

Reverse: saponification with
strong base

Ketone and aldehyde addition
reactions

Grignard Reaction

If chiral product, then racemic
mixture

nucleophilic reaction

Ester Grignard Reaction
-Reacts with 2 eq. grignard

nucleophilic reaction
Diagram Notes
Metal Hydride Reduction of
Aldehydes and Ketones/Esters

NaBH4 (aldehydes, ketones, acyl
chlorides, thioesters -> alcohol),
LiAlH4 (esters, carboxylic acids,
acyl chlorides,thioesters, ketones
-> alcohols; amide, nitro, nitrile,
imine -> amine)

nucleophilic reactions

Imine and Enamine (enol
analogue) formation from amines
and aldehydes/ketones

nucleophilic substitution

acetal formation
aldehyde/ketone + alcohol

nucleophilic reactions
Diagram Notes
Intramolecular hemiacetal
formation

carbon nucleophiles:
acetylide
cyanohydrin formation

nucleophilic addition

alpha/beta unsaturated
ketone/aldehyde additions

1,2 (direct) addition only with
strong base (grignard/H-)

1.4 (conjugate) addition with
most nucleophiles

a/b unsat ketones/aldehydes
formed from aldol condensation

decarboxylation reaction of 3-
oxo acids (beta-keto acid – type
of aldol)
Diagram Notes
diethyl malonate addition,
hydrolysis, decarboxylation

alpha hydrogen removal reaction

ketone/aldehyde alpha carbon
bond formation through imine
and electrophilic addition
Diagram Notes
aldol condensations – aldehydes,
ketones, mixed

Claissen Reaction – aldol with
esters
Diagram Notes
fatty acid synthesis

Important monosaccharides
Diagram Notes
Enediol Reactions
Diagram Notes
monosaccharide reactions
Diagram Notes
monosaccharide lengthening
- Kiliani-Fischer synthesis

*creates 2 C2 epimer products

monosaccharide shortening
- wohl degradation

rare natural amino acids
Diagram Notes
Amino acid synthesis from a 2-
oxo acid by reductive amination

Amino Acid synthesis from an
aldehyde – Strecker synthesis

Amidomalonic ester synthesis of
an amino acid
Diagram Notes
N-acylamino acid hydrolase
resolution of racemic amino acid

Laboratory Peptide synthesis
- N-protection

Solution phase peptide synthesis:
Activation, addition,
deprotection

(N->C)

tBOC-Leu-COO- + Cl-CH2-Ph-Bead ---> tBOC-Leu-CH2-Ph-Bead Solid phase peptide synthesis
--CF3COOH--> H2N-Leu-CH2-Ph-Bead --tBOC-Gly--> tBOC-Gly-Leu-CH2- (Merrifield synthesis) (C->N)
Ph-Bead --HF--> Gly-Leu
done in PS resin column
saves time (no purification)
high yield

HF deprotects and separates
peptide from PS