Pharmaceutical Organic Chemistry 125.

1
Pharmaceutical Organic Chemistry 1 Laboratory
Professor Bart David Quibod

Experiment 2: Structural Effects on Melting Point Review Questions:

and Boiling Point
1. Arrange the following compounds in order of
increasing melting point and/or boiling point
Quiz Answer Key:
assuming equal no. of carbon atoms: alcohol,
carboxylic acids, ethers, esters, aldehydes.
1-3. Draw the rough boiling point set-up
Explain.
- Simple distillation set-up:
- General arrangement of increasing boiling and/or
melting point: ether → ester → aldehyde → alcohol
→ carboxylic acid
- Explanation:
Carboxylic acid Hydrogen bonding
capabilities and the presence
of two oxygen atoms.

Alcohol Hydrogen bonding

capabilities. The presence of
only one oxygen atom
places alcohols below
carboxylic acids, which
have two oxygen atoms.
4-6. Arrange the following in order of increasing IMFA:
R-COOH, R-O-R, R-COOR, R-CHO, R-COR Aldehyde Lacking any hydroxyl
- R-O-R (ether) < R-COOR (ester) < R-CHO groups, aldehydes are
(aldehyde) = R-COR (ketone) < R-COOH incapable of intermolecular
(Carboxylic Acid) hydrogen bonds; the
presence of oxygen in the
7-8. Arrange in order of increasing boiling point: carbonyl group allows
1-butanol, isobutyl alcohol, tert-butyl alcohol aldehydes to accept
- Tert-butyl alcohol < isobutyl alcohol < 1-butanol hydrogen bonds from other
water molecules.
9-10. Arrange in order of increasing melting point:
p-aminobenzoic acid, benzoic acid, salicylic acid Ester Similar to ketones and
- Benzoic acid < salicylic acid < p-aminobenzoic acid aldehydes, esters are unable
to form intermolecular
11. Discuss the IMFA in carboxylic acids. hydrogen bonds. At the
- Dispersion (London) forces, Dipole-dipole same time, their
interactions, Intermolecular and Intramolecular dipole-dipole interactions
Hydrogen bonding are weaker than ketones and
aldehydes, thus placing
them below the latter and
above ethers.

Ether The lack of any

hydrogen-oxygen bond
makes hydrogen bonding
impossible.
2. What type of intermolecular attractive force is involved Additional Notes:
in carboxylic acids?
- Reciprocal H-bonding, VdW forces, dipole-dipole ● Factors affecting Boiling and Melting point:
interactions 1. Molecular Weight
- “Pag sinabi mong reciprocal sa pag-ibig, gusto mo - Direct relationship for both MP and
siya, tapos di niya binalik. O, one-sided; reciprocal ba BP
yun? Hindi. Dito ​[referring to carboxylic acid]​, 2 2. Branching
sides: carboxylic acid offers h-bonding and also - Increases melting point but
accepts h-bonding, both ways” (Quibod, 2018). decreases boiling point
3. Symmetry
3. Describe other melting point apparatus that are - Increases melting point but
available for routine analysis. decreases boiling point
a. Fisher-Johns melting point apparatus 4. Polarity
b. Thomas-Hoover melting point apparatus - Increases both MP and BP
c. Thiele tube melting point apparatus 5. IMFA
d. Barnstead-Thermolyne Mel-Temp melting point - The presence of IMFA increases
apparatus MP and BP
6. ortho-, meta-, para- position
4. Explain the differences in melting points and boiling - MP and BP of para- position >
points of these test compounds by relating with their ortho- position
structures and intermolecular forces of attraction: 7. Impurities
a. maleic acid and tartaric acid - Increase MP and BP
- Tartaric acid has a greater melting point than ● How do you know when the test sample is already
Maleic acid due to the presence of more OH boiling?
groups that allow more hydrogen bonding - The test sample will produce bubbles; it is
important to take note of the temperature at
b. p-aminobenzoic acid, benzoic acid, and salicylic which the bubbles start forming and also the
acid point at which it stops.
- PABA has the highest melting point due to - When there is moisture present on the
the amine group and the para- position. thermometer, the test sample is already
Salicylic acid has a higher melting point boiling
than benzoic acid because it allows for more - “COMMON SENSE PAG NAKITA NYO
H-bonding. NA NAGBOBOIL OR NAGBUBBLES,
TAWAGIN NYO NA AKO. MAGDASAL
c. naphthalene and 2-naphthol KAYO PAG NAGBUBBLES NA TAPOS
- 2-naphthol has a higher melting point WALA AKO” (Quibod, 2018).
because of the additional hydroxyl group ● Rough methods are “rough” because they simply are
connected to it. not accurate
- The distance of the thermometer from the
d. ethanol and 1-butanol sample is large
- 1-butanol has a higher boiling point than - In accurate methods, the thermometer is
ethanol because it is heavier due to its longer touching the sample
carbon chain.

e. 1-butanol, tert-butyl alcohol, and isobutyl alcohol

- Branching affects boiling point therefore
1-butanol has the highest boiling point
because it is a straight chain. Tert-butyl is
more branched than isobutyl alcohol, giving
it a lower boiling point.
Experiment 3: Structural Effects on Solubility
Quiz Answer Key
1. Water-soluble at __ g/100 ml
- 3.3 g/100 ml
2-4. Compare solubility of Benzoic acid and Sodium
Benzoate
- Na Benzoate is more soluble than Benzoic acid
- When salts such as sodium benzoate are dissolved in
water, their ions easily dissociate and readily interact
with the molecules of water.
5-7. Compare the solubility of o-nitrophenol and
p-nitrophenol
- p-nitrophenol is more soluble than o-nitrophenol
- The ortho- position induces intramolecular hydrogen
bonding thus decreasing solubility.
8-15. Descriptive Terms of Solubility
Experiment 4: Structural Effects on Acidity and
Basicity
Quiz Answer Key:
1-2. Phenol vs ethanol
- Phenol is more acidic than ethanol
- The benzene ring of phenol stabilizes itself due to the
delocalization of electrons
- “Ang reason ay yung benzene ring. Anong meron sa
piatos na yan? Meron kasi itong pi-electron
delocalization. Kung mas stable ang compound, mas
madali maglet go ng H. dahil prefer nito ang stable
resonance.” -Quibod, 2018
3-4. Phenol vs Benzoic Acid
- Benzoic acid is more acidic than phenol due to the
benzene ring (delocalization of electrons/resonance)
and due to the inductive effects of the carbonyl group
(carbonyl group is electron withdrawing thus
increasing acidity)

Very Soluble <1 5-7. Acetic acid vs chloroacetic vs trichloroacetic acid

- Trichloroacetic acid is the most acidic while acetic
Freely Soluble 1-10 acid is the least acidic
- Inductive effect; the electronegativity of chlorine
Soluble 10-30 increases acidity

Sparingly Soluble 30-100

Slightly Soluble
Very Slightly Soluble
Practically Insoluble
8-10. Urea vs Glycince vs Ammonium Hydroxide
100-1000 - Ammonium Hydroxide is the most basic while urea is
the least basic.
1000-10,000 - Urea is the least basic because the carbonyl carbon
already carries a slightly positive charge
≥​​ 10,000 - Ito is like Nh4OH kasi readily available ng yung OH,
tapos something about amines and amides

Additional Notes 11-13. O-cresol vs o-aminophenol vs nitrophenol

- O-aminophenol is the least acidic while nitrophenol
● Principle of solubility: “like dissolves like” is the most acidic
● Solubility → solute - solvent -
● Miscibility → liquid-liquid
Experiment 5: Structural Effects on Polarity ● Gypsum → calcium carbonate dihydrate
● Normal-Phase
Quiz Answer Key - Mobile phase is nonpolar while Stationary
phase is polar
1-3. Draw the set-up for TLC and explain the importance - Silica gel is the stationary phase
of the different parts - 5% acetic acid and 95% ethyl acetate is the
mobile phase
- In reverse-phase, the mobile phase is polar
while the stationary phase is non-polar

- “Syempre yung tlc plate mo dapat naka tayo sa tlc

chamber. Pag yan nahulog sa solvent, edi nababad na
yung compounds niyo. Common sense naman, di ko
nga alam kung bakit nandito sa book to eh” -Quibod,
2018

4-7. Rank amino acids based on Rf value

- Decreasing polarity: Glycine, Alanine, Tyrosine,
Phenylalanine

8. What is GF 254 nm in silica gel

- Gypsum fluorescence absorbs light at 254 nm

9. Give visualization techniques

- Ninhydrin spray reagent
- UV Light

10. Which phase will be used in the experiment:

normal-phase or reverse phase?
- Normal-phase

Additional Notes

● Chromatography: chromato- (color) and graphy-

(light)
● Principles involved in TLC are differences in polarity
and partition of components
● Types of Chromatography:
1. Partition
2. Adsorption
3. Affinity
4. Ion-Exchange
5. Size-Exchange
● In TLC, we use the spot-dry technique
● TLC plates are preheated to remove water