Honors Project: Organic Chemistry

Rebecca Nagurney & Anthony Possanza

Objectives

Synthesis of a precursor to an organic molecule with anti-cancer properties

Learn invaluable laboratory skills

Reinforce learning of lecture topics

Component of Turmeric Indian Spice

Anti-Cancer and Anti- Inflammatory Properties

Synthesis of Derivatives Acetyl Acetone

Curcumin

OO

X Y

X,Y = H,Cl;Cl,Cl;H,Br;Br,Br

O O

HO

CH3O

OH

OCH3

Synthesis of Curcumin

Halogenation Using N-Bromosuccinamide (NBS) or N-

Chlorosuccinamide (NCS)

N

O

O

X + HX X2 N

O

O

H+

X2

OO

H H

+

OO

X Y

X,Y = H,Cl;Cl,Cl;H,Br;Br,Br

Chlorination Chlorinating Reagent:

N-Chlorosuccinamide (NCS) Reaction: 1.0193g Acetyl Acetone + 1.5094g NCS +

15mL dichloromethane (CH2Cl2) Stir reaction for one week at room

temperature Use thin layer chromatography (TLC) to

check for product

Bromination Brominating Reagent:

N-Bromosuccinimide (NBS) Reaction: .5112g Acetyl Acetone + .8342g NBS +

15mL THF (Tetrahydrofuran) Stir reaction for one week at room

temperature TLC to check for product

Thin Layer Chromatography Solvent system: 10:1 (Hexane: Ethyl Acetate

(EtOAc)) Spot

Starting Materials (Acetyl Acetone in EtOH) Reaction Mixture

TLC Continued Allow solution to run up the TLC plate Mark the solvent front before removing from the

solution Dry Dip in 5% Phosphomolybdic Acid in EtOH Place on hot plate and wait for spots to appear Calculate Rf Value

Rf = d1/d2 d1 = distance from origin to middle of

spot d2= Distance from origin to solvent front

TLC of Bromination Reaction in Tetrahydrofuran (THF)

Removing the Solvents Rotary Evaporator

“Roto Vap”

Column Chromatography Fill column with gel Load dry or wet

Wet is better!!! Particles are fine and can get into

your lungs!! Run hexane through the column until the

gel is compacted Pour a layer of sand on top of the

compacted gel

Column Chromatography Load product on top of sand Run hexane through the column and

collect samples Add 25mL Ethyl Acetate to Hexane to

increase polarity of the solvent Increase to a 50% Hexane 50% Ethyl

Acetate solution 57 samples were taken

TLC of Bromination Reaction in Acetone

Results Reaction in THF

Favors mono-bromo product Slower moving (more polar) spot on

TLC Reaction in Acetone

Favors di-bromo product Faster moving (less polar) spot on TLC

Future Work

Continuation of honors work into the spring semester

Completion of synthesis of anti-cancer agent

We would like to sincerely thank Dr. Pham for her guidance and support