synthesis of aspirin - dr. oya irmak Şahin-cebeci – · pdf file ·...
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SYNTHESIS OF ASPIRINSYNTHESIS
PURIFICATION
CHARACTERIZATION
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ASPIRIN: SOME BACKGROUND
• PATENTED BY BAYER IN 1893
• ONE OF THE OLDEST DRUGS
• ONE OF THE MOST CONSUMED DRUGS (PRODUCTION IN THE US IS
10 MILLION KG/YEAR)
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ASPIRIN: BIOLOGICAL ACTIVITY
• ANALGESIC (PAINKILLER)
• ANTIPYRETIC (FEVER REDUCER)
• ANTI-INFLAMMATORY (INHIBITION OF THE SYNTHESIS OF
PROSTAGLANDINS)
• SIDE EFFECTS: GASTRIC IRRITATION, BLEEDING
APPARITION OF NEW ANALGESICS (TYLENOL)
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ASPIRIN: THE MOLECULE
O
OH
O
O
acetyl salicylic acid (aspirin)
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ORGANIC BACKGROUNDALCOHOLS
• ALCOHOLS
• ALIPHATIC ALCOHOLS: HYDROXYL DERIVATIVES OF SATURATED
HYDROCARBONS
• ENOLS: HYDROXYL DERIVATIVES OF UNSATURATED HYDROCARBONS
R OH
H3C OH
methanolOH
ethanol
OH
R
R
enol
OH
phenol
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ORGANIC BACKGROUNDCARBOXYLIC ACIDS
O
OH
O
OHH
O
OH H.C
O
OH
formic acid acetic acid
benzoic acid
R
O
OH
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ORGANIC BACKGROUNDESTERIFICATION
R1
OH
O
HO R2 R
1O
O
R2
carboxylic acid alcool ester
H+
+
This is an equilibrium!
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ORGANIC BACKGROUNDESTERIFICATION MECHANISM
R1
OH
O
HO R2
R1
O
O
R2
carboxylic acid alcool
ester
R1
OH
OH
O
H+
R2
H
+
R1
OH
OH2+
O
R2
-H+
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ORGANIC BACKGROUNDACIDITY: A REVIEW
• BRONSTED-LOWRY ACID
SUBSTANCE THAT CAN DONATE A PROTON
• LEWIS ACID
SUBSTANCE THAT ACCEPTS LONE-PAIR ELECTRONS
• AH + H2O A- + H3O+
KA= [H3O+][A-] / [AH]
PKA= -LOG KA
Acid pKa
water 14.0
Acetic acid 4.75
Benzoic acid 4.19
Formic acid 3.75
Sulfuric acid 1
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REACTION
OH
OH
O
salicylic acid
O
O O
acetic anhydride
O
OH
O
O
acetyl salicylic acid (aspirin)
OH
O
acetic acid
H2SO4
heat+ +
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REACTION MECHANISM
OH
HO
O
O
O
O
O
HO
O
O
OH
O
H+
O
HO
O
H+ OH
O
O
+
-H+
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SYNTHESIS PROCEDURE
• MIX SALICYLIC ACID (SOLID) WITH ACETIC ANHYDRIDE (LIQUID) AND A
CATALYTIC AMOUNT OF H2SO4.
• HEAT FOR 10 MIN AT 900C.
• COOL DOWN TO ROOM TEMPERATURE AND ADD WATER
(CRYSTALLIZATION SOLVENT).
• INDUCE CRYSTALLIZATION.
• FILTER THE CRYSTALS.
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PURIFICATION BY RECRYSTALLIZATION
WHAT IS RECRYSTALLIZATION?
➢ RAPID AND CONVENIENT WAY OF PURIFYING A SOLID ORGANIC COMPOUND
➢ THE MATERIAL TO BE PURIFIED IS DISSOLVED IN THE HOT APPROPRIATE SOLVENT
➢AS THE SOLVENT COOLS, THE SOLUTION BECOME SATURATED WITH RESPECT TO THE SUBSTANCE, WHICH THEN CRYSTALLIZE
➢ IMPURITIES STAY IN SOLUTION
METHOD
➢CHOOSE THE SOLVENT
➢DISSOLVE THE SOLUTE
➢(FILTER SUSPENDED SOLIDS)
➢CRYSTALLIZE THE SOLUTE
➢COLLECT AND WASH THE
CRYSTALS
➢DRY THE CRYSTALS
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ASSESSMENT OF PURITY: LOOKING FOR PROPERTIES
PHYSICAL PROPERTIES
• PHYSICAL APPEARANCE
• SOLUBILITY
• MELTING POINT
• INFRARED SPECTRA
CHEMICAL PROPERTIES
• PERCENT YIELD
• POTENTIOMETRIC
TITRATION
• PHENOL TEST
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ASSESSMENT OF PURITY: PHYSICAL APPEARANCE
• PHYSICAL STATE (SOLID? LIQUID? ..)
• COLOR
• ODOR
• TEXTURE
• HOMOGENEITY IN COMPOSITION
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ASSESSMENT OF PURITY: SOLUBILITY (NON MANDATORY)
• IN A TEST TUBE, TRANSFER A SMALL AMOUNT OF YOUR
PRODUCT (END OF A SPATULA)
• ADD ~1/2ML OF SOLVENT
• DETERMINE SOLUBILITY AT ROOM TEMPERATURE
• IF NOT, GENTLY HEAT AND DETERMINE SOLUBILITY AT HIGHER
TEMPERATURE
• TEST SEVERAL ORGANIC SOLVENTS AND COMPARE WITH
LITTERATURE
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ASSESSMENT OF PURITY: MELTING POINT
• MELTING POINT CHARACTERIZE THE COMPOUND
• RANGE OF THE MELTING POINT INDICATE THE PURITY OF THE
COMPOUND
• METHOD: SCANNING OF THE TEMPERATURE UNTIL MELTING
OCCURS. DETERMINE START AND END TEMPERATURE OF
MELTING.
• DON’T HEAT TOO FAST!! (<10C / MIN)
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ASSESSMENT OF PURITY: INFRARED SPECTRA
• DISSOLVE THE PRODUCT IN CHLOROFORM AND
OBTAIN THE IR SPECTRUM. YOU CAN ALSO
PREPARE A PELLET IN KBR.
• ASSIGN THE PEAKS
• DO YOU SEE IMPURITIES?
• COMPARE WITH THE REFERENCE SPECTRUM.
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ASSESSMENT OF PURITY: PERCENT YIELD
• DEFINITION: %YIELD = NEXP/NTH
• WRITE DOWN THE REACTION WITH THE CORRECT STOECHIOMETRY. EX: A+B C
• PREPARE A CHART LIKE BELOW AND CALCULATE YIELD.
mA (g)
or VA
(mL)
nA
(mol)
mB (g)
or VB
(mL)
nB
(mol)
mC (g)theoretical
nC (mol)theoretical
mc (g)experimental
nC (mol)experimental
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ASSESSMENT OF PURITY: PHENOL TEST AND VISIBLE
SPECTROSCOPY
• PHENOL REACT WITH FECL3 (AQ) TO GIVE A DEEP PURPLE
COMPLEX.
• PHENOL IS NOT PRESENT IN THE PRODUCT BUT IN ONE OF THE
REACTANT.
• THIS TEST INDICATE THE PRESENCE OF UNREACTED STARTING
MATERIAL (QUANTITATIVE ANALYSIS POSSIBLE VIA VISIBLE
SPECTROSCOPY).
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OH
OH
O
salicylic acid
+ Fe3+ Deep purple complex
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ACETYLSALICYLIC ACID(MORE COMMONLY KNOWN AS ASPIRIN)
BY VIKTOR POLITES
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CHEMICAL STRUCTURE
• FORMULA: C9H8O4
• SYSTEMATIC NAME:
2-ACETOXYBENZOIC ACID
• HAS A BENZENE RING
BACKBONE
• CARBOXYLIC ACID
• ESTER GROUP ON THE 2ND
CARBON IN BENZENE RING.
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PHYSICAL PROPERTIES
Density: 1.40 g/cm3
Melting Point: 135 °C
Boiling Point: 140 °C
Solubility in Water: 3 mg/mL at 20 °C
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CHEMICAL PROPERTIES
• ACETYLSALICYLIC ACID SLOWLY DECOMPOSES BY
HYDROLYSIS INTO ACETIC AND SALICYLIC ACIDS IN THE
AQUEOUS MEDIUM.
• HYDROLYSIS OF ACETYLSALICYLIC ACID IS ACCELERATED IN
SOLUTIONS OF AMMONIUM ACETATE, OR ACETATATES,
CARBONATES, CITRATES, OR HYDROXIDES OF THE ALKALI
METALS.
• ACETYLSALICYLIC ACID IS A WEAK ACID WITH AN ACID
DISSOCIATION CONSTANT, KA, OF 3.2 X 10^-4.
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