Chemical synthesis

1) Safety: PPE; lab coat, gloves, googles, covered shoes. DANGEROUS CHEMICALS USED.

2) Organic synthesis introduction

The molecule to be synthesized in organic synthesis is called the target compound. The target compound
is usually derived from a starting material. Transformation of one functional group to another is a
common practice in organic synthesis.

(Scifinder--> used for literature search)

3) General process of chemical synthesis reaction (solution phase synthesis):

Adding substance into an organic solvent until fully dissolvedset the conditions for synthesis (eg
temperature; cold [0 to -20], room temperature [25], hot [50, 100, 200]) adding of reagents for
reaction quenching(stopping) of reactionpurification using separating funnel of organic and
aqueous phasespurification using silica column characterization (LCMS/ NMR/ HPLC/ FTIR).

4) Common glassware used

Round Bottom Flask (RBF) for even heat distribution for heating of chemicals

Claisen adapter It is used in situations which require more than one outlet from a round-bottom
flask.

Distillation adapterThe adapter connects the distillation flask, the condenser, and the thermometer.

Separatory funnel Separatory funnels are used in the lab for liquid-liquid extractions, separating a
mixture's components into two solvent phases of different densities (organic and aqueous phase).

Distillation Column A distillation column is used to distill or separate liquid mixtures into the individual
components comprising the total mixture.

5) Common solvents used, structure, Boiling point, function in chemical synthesis

Ethyl acetate CH₃CO₂CH₂CH₃ 77.1 °C highly miscible, used

for extractions
Acetonitrile CH₃CN 82 °C a source of nitrogen
Toluene C₆H₅CH₃ 110.6 °C synthesis of benzene
and other chemicals,
dissolve other organic
compounds
Tetrahydrofuran C4H8O 66 °C miscible with water
and most organic
solvents, solvent for
Grignard and Wittig
reactions.
Diethyl ether (C2H5)2O 34.6 °C The oxygen atom of
diethyl ether forms a
complex with the
 magnesium atom of
the Grignard reagent
Ethanol C₂H₆O 78.37 °C Common intermediate
for reactions
Dimethylformamide C3H7NO 153 °C a reagent in the
Vilsmeier–Haack
reaction, catalyst, and a
stabilizer
DCM, methanol solvent to dissolve compounds.

6) Conditions of organic synthesis

1) Temperature (endothermic/ exothermic)

2) solvents used (Little/ mild/ high/ explosive)

3) Type of reactions (Grignard, Suzuki, Redox)

4) reactivity of the compounds added together

7) Types of chemical reactions

Name of reaction, conditions, structure, Quenching

Grignard reaction Aldehyde Aldehyde to primary Add water, DROPWISE

(Formaldehyde or alcohol
methanal), Aldehyde Aldehyde to secondary
(Acetaldehyde or alcohol
ethanal), Ketone Ketone to tertiary
(Butanone), Strong alcohol
nucleophile, Undergoes
addition reaction to
carbonyl groups (C=O),
Ether solvent
Suzuki reaction Boronic acid, carbon-carbon single The most common
organohalide, bond is formed by quenching agent used
palladium (catalyst) coupling a halide (R1-X) for Suzuki reactions is
with aqueous acid, typically
an organoboron species dilute hydrochloric acid
(R2-BY2) using (HCl) or sulfuric acid
a palladium catalyst (H2SO4).
and a base.
Staudinger Azides, The Staudinger Add Quenching Agent:
triphenylphosphine, reduction of Common quenching
water azides involves the agents for Staudinger
conversion of azides reactions include acids
into amines by like acetic acid,
treatment with a hydrochloric acid (HCl),
phosphine and water. or sulfuric acid
(H2SO4).
Nucleophilic Nucleophiles: SN2: is a single step Add Quenching Agent:
substitution hydroxide ions, cyanide displacement of a Acidic Quenching: If
ions, water, and leaving group by a under basic conditions,
ammonia nucleophile, fully adding acid, such as
inverted structure. hydrochloric acid (HCl)
SN1: a twostep reaction or sulfuric acid
in which 1. The leaving (H2SO4).
group leaves, forming a Basic Quenching: If
carbocation, then the under acidic
nucleophile attacks the conditions, you can
carbocation forming a quench it by adding a
racemic mixture base: sodium
bicarbonate (NaHCO3)
or sodium hydroxide
(NaOH).
Neutralizing
Quenching: For under
neutral conditions, use
neutralizing agents
include sodium
carbonate (Na2CO3) or
potassium carbonate
(K2CO3).
Electrophilic Functional group, Electrophilic Removal of the proton,
substitution electrophile, substitution of benzene Presence of nitro group
displacement by occurs where an in a benzene ring
hydrogen electrophile substitutes withdraws electron
the hydrogen atom of density from the
benzene. benzene ring
Oxidation Function group Lose electron, gain Reducing Agent
transformation, oxygen, lose hydrogen, Quenching: sodium
reduction increase oxidation state bisulfite (NaHSO3) or
sodium thiosulfate
(Na2S2O3), can help
neutralize excess
oxidizing agents and
reduce any remaining
oxidized species.
Reduction Function group Gain electron, lose Oxidizing Agent
transformation, oxygen, gain hydrogen, Quenching: Adding a
oxidation decrease oxidation suitable oxidizing
state agent, such as
hydrogen peroxide
(H2O2), can help
neutralize excess
reducing agents and
prevent further
 reduction.
Hydrolysis Water, organic Organic compound Add Quenching Agent
compound, high with 2 functional group Acidic Quenching:
temperature. + water 2 different Adding hydrochloric
alcohols acid (HCl) or sulfuric
acid (H2SO4), can help
neutralize any
remaining base or basic
intermediates.
Basic Quenching:
Adding sodium
hydroxide (NaOH) or
sodium bicarbonate
(NaHCO3), can
neutralize any
remaining acid or acidic
intermediates and stop
the hydrolysis reaction.

Diels-Alder reaction

8) Analytical instruments characterization

8.1) LCMS

8.2) HPLC & TLC

8.3) NMR 1H

8.4) FTIR
Common functional groups
Functional group transformation (REDOX) of alcohols

Hydrolysis
Selective protection of guanosine procedure

Require: 1 magnetic stir bar, rubber septum, 250ml RBF, nitrogen environment, needles (1 for nitrogen, 1
for DMF-DMA), 1g of compound, 30ml of methanol, 3ml of DMF-DMA, 50ml measuring cylinder.

1) Measure 1g of compound, 30ml of methanol, 3ml of DMF-DMA (syringe and needle).

2) Setup the RBF with septum and magnetic stir bar.

3) Clean magnetic stir bar and place in RBF in the magnetic stirrer

4) Pump nitrogen through the RBF

5) Add the compound into the RBF

6) Add the methanol into RBF (suspension)

7) Slowly add DMF-DMA into suspension (check for heat [exothermic reaction])

8) Leave overnight for 18h

Chemical formula of reaction

Before:

TLC under UV light: SM starting material, RM reaction mixture, Y-> starting material+ reaction
mixture
LCMS spectrum of compound=446m/z. Molecular weight= 447. Expected mass to charge ratio for
negative mode= (447-1)/1= 446m/s.