|
Signature |
Case |
Date |
Sr.no |
|
|
Definitions and commonly
employed calculations in medicinal chemistry. |
|
1 |
|
|
Determination of molecular
weight of given liquid by neutralization equipment method. |
|
2 |
|
|
Determination of molecular
weight of dibasic acid by neutralization equivalent method. |
|
3 |
|
|
Determination of molecular
weight of tribasic acid by neutralization equivalent method |
|
4 |
|
|
Synthesis of sodium salicylate. |
|
5 |
|
|
Synthesis of dibenzalacetone
and its medicinal value. |
|
6 |
|
|
Synthesis of benzhydrol and
study its medicinal uses. |
|
7 |
|
|
Synthesis of benzylic acid and
study its medicinal value. |
|
8 |
|
|
Synthesis of phenytoin. |
|
9 |
|
|
Synthesis of paracetamol. |
|
10 |
EXPERIMENT 1
DEFINITION AND COMMONLY EMPLOYED CALCULATIONS IN MEDICINAL CHEMISTRY.
MOLARITY:
Number of
moles of solute dissolved in one litre of solution.
MOLARITY OF SOLID:
Molarity (M)= Number of moles of solute.
1litre of
solution
Moles= Mass in grams
Molecular weight
Molarity M = Mass in grams/Molecularweight
1 litre of solution
|
Weight required= Molarity*Molecular
weight*1litre of solution |
Example:
For 0.2 M NaOH:
Weight
required= Molecular weight*Molarity*1litre
= 40*0.2*1
= 8gms/1L
MOLARITY OF LIQUIDS:
MB= %
purity*density*10
Molecular
weight
Example:
For 2M HCl (in 100ml):
Density=
1.19 g/cm
% purity=
37%
MB=37*1.19*10/38.5
=12.06in 1000ml 0f water.
MB*VB= moles
required *volume required
VB= moles required*volume required/MB
=2*100/12.06
VB= 16.6ml in 100ml water to make 2M HCl solution.
*make up the
volume upto 100ml
NORMALITY:
Number of
gram equivalent of a substance dissolved in 1 litre of solution.
NORMALITY OF LIQUID:
N= Number of gram equivalent
1 litre of
solution
Gram equivalent=
Molecular weight
Number of
replaceable H+ and OH-
Molecular
weight= 98g/mol
Gram
equivalent=98/2
= 49
NB= %Purity*Density*10
Gram
equivalent
= 96*1.84*10
49
= 36.04
NB*VB= Normality required*Volume required
NB
= 1*100/36.04
VB=2.77ml in 100ml water to make 1N H2SO4
*make up
volume upto 100ml
NORMALITY OF SOLIDS:
N= Number of gram equivalent
1 litre of
solution
Gram equivalent= Molecular weight
Number of
replaceable H+ and OH-
Example:
For 0.1 N
Ca(OH)2 (100ml)
Molecular
weight= 72g/ml
No of
replaceable ions= 2
Gram
equivalent= 72/2
= 36
Weight
required= Normality *Gram equivalent* 1litre
=0.1*36*1
litre
=3.6g/1000ml
If 1000ml
contains=3.6g of Ca(OH)2
1ml
contains=3.6/1000 of Ca(OH)2
100ml
contains=3.6/1000*100 of Ca(OH)2
=0.36gms/100ml
of Ca(OH)2
EXPERIMENT 2
DETERMINATION OF MOLECULAR WEIGHT OF LIQUID BY NEUTRALIZATION EQUATION
METHOD.
NORMALITY:
A chemical
agent that can be weighed with analytical accuracy yielding an accurate
standard of known normality.
Standard
solution prepared after being standardization against primary standard.
Example:NaOH/HCl
Monobasic acid:
Acid that
has ability to neutralize one molecule of base.
Standardization:
Chemical equation:
COOH COONa
2NaOH + .2H20 + 4H2O
COOH COONa
Principle:
Acid base
titration
Indicator:
Phenolphthalein
End point:
Preparation of solution:
0.2M NaOH solution:
Prepare the
solution approx. 0.2M sodium hydroxide in 250ml volumetric flask dissolving 2g
of NaOH and make volume upto 250ml of distilled water. This should be
standardized by titration with 0.1M oxalic acid using phenolphthalein
indicator.
0.1M Oxalic acid solution
Prepare the
solution of approx.. 0.1M oxalic acid in 100ml volumetric flask by dissolving
1.26g of oxalic acid in 100ml of distilled water for standardization of
secondary standard NaOH.
Procedure:
1. Weigh out accurately about 2g of pure
organic acid benzoic acid,dissolve it in ethanol and transfer the solution to
100ml graduated volumetric flask.
2. Ensure the solution is homogeneous and make
upto the required volume. Use a pipette to measure out 25ml aliquot and
transfer it to flask.
3. Using two drops of phenolphthalein solution
as indicator,titrate with standard (0.2M NaOH) until the colorless solution
becomes fairly pink.
4. Repeat this process three times to get
average result.
Calculate
molecular weight of organic acid using following formula.
Molecularweight=
W=weight of
acid taken
P= number of
carboxyl groups.
V=volume of NaOH
used.
M= molarity
of NaOH used.
LIMITING REACTANT
The reactant
in a chemical reaction that limit the amount of product that can be formed.The
reaction will stop when all of the limiting reactant is consumed.
Example:
Synthesis of
Ammonium chloride.
NH3+HClNH4Cl
Quantities:
1.7gms NH3
29.75gms HCl
Molecular weight:
17gms NH3
36.5gmsHCl
Number of moles:
NH3=
1.7gms/17gms
= 0.1moles
HCl= 29.75gms/36.5gms
= 0.81gms.
NH3 is a limiting reactant in a reaction.
Theoretical and Analytical yield:
Theoretical yield:
Theoretical
yield is the quality of product that could be synthesized under ideal
conditions.
Actual yield:
Actual yield
is the actual amount of product synthesized in the experiment.
Percentage yield:
Percentage
yield is the ratio between the actual and theoretical yield multiplied by 100.
It indicates
the percent of actual yield that was obtained from the final product in an experiment.
Synthesis of Sodium benzoate
Molecular
weight of benzoic acid=122gms
Molecular
weight of sodium benzoate= 144gms
Mass o
benzoic acid taken= 3gms
Theoretical yield:
122gms of
benzoic acid yield sodium benzoate= 144gms
1gms of
benzoic acid yield sodium benzoate= 144/122
3gms of
benzoic acid yield sodium benzoate= 144/122*3
=3.54gms
Actual
yield= 3.54gms
Percentage yield = Actual yield*100
Theoretical
yield
= 3.43/3.54*100
Percentage
yield =97%
Theoretical yield = Number of moles*molecular mass
=0.1*53.5
=5.35gms.
Actual yield:4.9gms
Percentage
yield = Actual yield/theoretical yield *100
= 4.9/5.35*100
= 91%
EXPERIMENT
3
DETERMINATION OF MOLECULAR WEIGHT OF
DIBASIC ACID BY NEUTRALIZATION EQUIVALENT METHOD
Dibasic acid :
Acid that has ability to neutralize two
molecules of a base.
Standardization:
COOH COONa
2NaOH + .2H20 +4H2O
COOHCOONa
Principle:
Acid base titration.
Indicator:
Phenolphthalein
End point:
Light pink
Preparation of solution:
►0.2 M NAOHsolution:
Prepare the solution approximately 0.2M NAOH in
250ml volumetric flask dissolving 2g of NAOH in 250ml of distilled water. This
should be standardize by titration with 0.1M oxalic acid using phenolphthalein
as indicator.
►0.2M oxalic acid solution:
Prepare the solution of approximately 0.1M oxalic
acid in 100ml volumetric flask by dissolving 1.26g of oxalic acid in 100ml of
distilled water. Standardization of secondary standard (NAOH solution).
Test titration:
+ 2NAOH → 
+2H20
Principle:
Acid base titration.
Indicator:
Phenolphthalein
End point:
Light pink
Procedure:
►Weigh out accurately about
2g of pure organic acid (phthalic acid).Dissolve it in ethanol and transfer the
solution to 100ml graduated cylinder/ volumetric flask.
►Ensure the solution is
homogenous and make upto required volume. Use a pipette to measure out 25ml
aliquot and transfer to flask.
►Using two drops of
indicator, titrate with standard (02M NaOH)until colorless solution becomes
fairly pink.
►Repeat the procedure 3
times to get average results.
►Calculate molecular weight
of organic acid by formula.
Molecular
weight =
M = Molarity of NAOH used
V = Volume of NAOH used
W = Weight of acid taken
P = No. of carboxyl
group.
EXPERIMENT 4
DETERMINATION
OF MOLECULAR WEIGHT OF TRI BASIC ACID BY NEUTRALIZATION EQUIVALENT METHOD.
Tri basic Acid:
Acid that has ability to neutralize
three molecules of a base.
Standardization:
2NaOH
+ C00H.2H2O àCOONa +4H2O
C00H COONa
Principle:
Acid -Base titration.
Indicator:
Phenolphthalein
End point:
Light pink
Preparation of Solution:
0.2M NaOH solution:
Prepare the solution Approximately 0.2M NaOH in 250ml volumetric
flask dissolving 2g of NaOH in 250ml of Distilled water, this should be standardized
by titration with 0.1M oxalic acid using Phenolphthalein as an indicator.
0.1M Oxalic acid solution:
Prepare the solution of approximately 0.1M oxalic acid in 100ml
Volumetric flask by dissolving 1.26 of oxalic acid in 100ml of distilled water.
Standardization of secondary standard (NaOH) solution.
Test Titration:
Procedure:
1.
Weigh out
accurately 2g of pure organic acid (Citric acid). Dissolve it in ethanol and
transfer the solution in 100ml graduated cylinder.
2.
Ensure that the
solution is homogenous and make up to required volume. Use a pipette to measure
25ml aliquot and transfer to the flask.
3.
Using two drops
of indicator titrate with standard 0.2M NaOH until colorless solution becomes
fairly pink.
4.
Repeat the
procedure 3 times to get the average results.
Calculate molecular weight of organic acid by using formula:
Molecular Weight=
W
=weight of acid taken
P=No
of Carboxyl Group
V=
Volume of NaOH used
M=
Molarity of NaOH used
EXPERIMENT 5
SYNTHESIS OF SODIUM SALICYLATE
IUPAC NAME:
Sodium 2-Hydroxy Benzoate
Apparatus:
China Dish, Conical Flask, Glass Rod, Beakers, Stirrer
Chemicals Required:
Salicylic Acid……………….3g
Na2CO3 …………………………………2g
Distilled Water………………5ml
Chemical Equation:
Procedure:
1. Take Salicylic Acid 3g and make its paste with distilled water 5ml.
2. Add Sodium bicarbonate 2g already dissolved in distilled water (10 ml).
3. Stir the reaction mixture by glass rod by heating on low flame till
evolution CO2.
4. Scratch the solid and calculate the percentage yield by formula
Formula:
Uses:
1. Anti-Inflammatory
2. Analgesic
EXPERIMENT6
SYNTHESIS OF DIBENZAL ACETONE AND STUDY OF ITS MEDICINAL USES.
Apparatus:
·
Measuring
cylinder
·
Funnel
·
Pipette
·
Beaker
·
Conical flask
·
Filter paper
·
Magnetic
stirrer
·
Weighing
balance
Chemicals:
·
Sodium
hydroxide
·
Benzaldehyde
·
Methanol
·
Acetone
·
Distilled water
Chemical equation:
Procedure:
1.
In a 250 ml
flask containing magnetic stirrer. Place another solution of 5g of NaOH in 50ml
distilled water and 30ml of methanol.
2.
Slowly remove
one half of the solution.
3.
To the
remaining half of the solution add 5.1ml benzaldehyde dropwise and then 1.5ml
acetone.
4.
Flocculated
precipitates will be produce in the mixture.
5.
Stir
continuously for 15 minutes.
6.
Then add
remaining solution into the above mixture.
7.
Stir for 30
minutes.
8.
Filter the
precipitates and wash them to eliminate the alkali as completely as possible.
9.
Dry the solid
precipitates and weight them.
10.
Calculate the
percentage yield.
IUPAC Name:
·
1,5-Diphenyl-1,4-diene-zone
Pharmacological use:
·
Sunscreen
component.
EXPERIMENT7
SYNTHESIS OF BENZHYDROL AND STUDY IT’S MEDICINAL USE.
IUPAC name:
Diphenyl methanol
Apparatus:
- Measuring
cylinder
- Pipette
- Funnel
- Filter
paper
- Conical
flask
- Measuring
balance
- Beaker
- Stirrer
Chemicals Required:
·
Benzophenone
·
Concentrated HCL
·
Zinc (dust)
·
Ethanol
·
NaOH
·
Cold water
Chemical Equation:
Procedure:
- In
250ml flask equipment with a reflux condenser and a mechanical stirrer
place benzophenone 5 g. Stir the mixture ethanol 95%, NaOH 5g for 20-25
min or until it turns brown.
- When
the temperature has commenced to fall, filter the reaction mixture with
suction.
- Add
5g zinc dust then heat again until dark brown color disappears (usually
2-3 hrs.).
- Wash
the residue twice with 10 ml portion of ethanol.
- Pour
the alternate into ice cold water 200 ml and acidified with concentrated
HCl.
- The
benzhydrol will separate initially as viscous oil on further cooling it
solidifies.
- Collect
the crude drug product by suction filtration and recrystallize it from hot
ethanol 10 ml.
- Dry
the recrystallized product between the folds of filter paper.
Pharmacological uses:
Ø It has been used in formulation and the pharmaceutical
manufacturing.
Ø In pharmaceutical manufacturing it is used as a fundamental
component in antihistamine, antihypertensive and anti-allergy agents.
EXPERIMENT: 8
SYNTHESIS OF BENZILIC ACID AND
STUDY OF ITS MEDICAL USES
IUPAC NAME:
2-hydroxy-2,2 diphenyl ethanoic
acid.
Apparatus:
Round bottom flask, reflux
condenser, heating mantle, beaker, pipette, Buchner funnel,
filter paper.
Chemicals:
·
Benzyl
·
Ethanol
·
Potassium
hydroxide
·
Conc.
Hydrochloric acid
·
Dist. Water
Chemical equation:
Mechanism:
Procedure:
1.
Take 3ml of
benzil in 10ml of ethanol (95%) in a 250ml round bottom flask.
2.
Stirr the
mixture and attach the flask with reflux condenser and heat it until benzil
gets dissolved.
3.
Dissolve 3g of
KOH in 10ml water and ethanol (10ml) to it, now add this solution dropwise into
reflux mixture and heat it for 15 minutes.
4.
Reaction is
completed when blue-black color appears.
5.
Detach the reflux
condenser and cool the contents of round botton flask.
6.
Transfer the
mixture into the beaker and keep it in ice bath for 15 minutes.
7.
When
crystallization gets completed and visually the mixture seems to be solidified
collect the crystals and wash with 15ml of 95% ethanol three times.
8.
Transfer the
solid content to a flask of hot water, stir till the crystals get dissolved.
Now add 15ml of 2M HCl dropwise into mixture of potassium benzillate.
9.
Allow it to
cool in water bath for 30 minutes.
10.
Collect the product
and wash with 30-40ml of water to remove impurities.
Uses:
It is used in manufacturing of
pharmaceuticals including Clidium (anticholinergic drug for abdominal cramps),
phenytoin and flutropium (animuscuranic drug for bronchial dilatation).
EXPERIMENT 9
SYNTHESIS OF
5,5-DIPHENYLHYDANTOIN (PHENYTOIN)
IUPAC Name:
5.5-diphenyl imidazolidine-2,4-dione
Common Name:
Dilantin
PHENYTOIN:
Synthesis:
Procedure:
1.
Dissolve 2g of
benzyl, 2g of sodium hydroxide and1.5g of urea in dry ethanol (absolute) 150ml
in a round bottom flask, heat gently the mixture on steam bath for 1 hour.
2.
After that,
mixture is placed on ice bath,volume is made 100ml with ice water mixture.
3.
Filter the
solution to remove impurities.
4.
Filterate is
acidified by dropwise addition of conc.HCl (5.5-6) to precipitate the solution
as white solid (product).
5.
Separate it by
filteration and wash with water thrice. Dry the product, weigh it, and
calculate % yield.
Uses:
·
Anticonvulsant
drug used to control seizures.
·
Used to treat trigeminal
neuralgia and other cranial neuralgia.
·
Used as
antiarrhythmic drug.
·
Used to treat
neuropathic conditions e.g. diabetic neuropathy.
ADVERSE DRUD
REACTIONS:
Neurologic:
·
Nystagmus
·
ophthalmoparesis
·
Cerebellar
ataxia
·
Seizures
Hematologic:
·
Folic acid deficiency.
(megaloblastic anemia)
·
Leucopenia
·
Thrombocytopenia
·
Gingival
enlargement
MECHANISM OF
ACTION:
It suppress abnormal brain activity,
seen in seizures by reducing electrical conductance among brain cell by
stabilizing inactive state of voltage gated ion channels.
STRUCTURAL ACTIVITY RELATIONSHIP:
R1=H
R2=C6H5
R3=C6H5
As phenyl or other aromatic
substitution is essential for activity. Alkyl substitution may contribute to
sedation, a property absent in phenytoin.
EXPERIMENT 10
SYNTHESIS OF PARACETAMOL AND STUDY OF ITS STRUCTURAL ACTIVITY
RELATIONSHIP (SAR).
Introduction:
Paracetamol is very widely used
analgesic and antipyretic. It is a relatively safe drug though toxicity has
been observed with very high dose.
Physical properties:
Pure
paracetamol is a white crystalline solid which melt at 169ºC. It is sparingly
soluble in cold water but in hot water its solubility is about 5g/100ml. It is
quite soluble in ethanol 14g/100ml.
The
drug Acetaminophen was formly used as antipyretic to relieve fever but long
term use of phenacetin cause kidney damage and urothelial neoplasm. In 1893
Joseph Von Mering discovered paracetamol, which was found to be not only a good
antpyretic but also a much safer one than phenacetin.
Synthesis:
Procedure:
1.
1g of
4-aminophenol and 9ml of distilled water was placed in 50ml conical flask and
stirring briskly at room temp, in order
to suspend the solid in water.
2.
In a fume
covered, 1.17g (1.1ml) of acetic anhydride or acid chloride was added to
stirred suspension and gently shake to mix. The solid got dissolved after about
30 sec, shaking was continue until precipitate was formed.
3.
After 10 min.
the solid was filtered off under suction, washed with little cold water and
dried.
4.
The product was
purified by distillation by dissolving crude product in minimum of distilled
water at about 80º C.
5.
The clear
solution was allowed to cool slowly to room temperature and recrystallized
product was collected by suction filteration.
6.
The
recrystallized product was dried between filter papers and then yield was
determined.
Paracetamol toxicity:
N-acetyl-p-benzoquinone
imine (NAPQI) is a toxic byproduct produced during xenobiotic metabolism of
paracetamol.
It
is normally produced only in small amount and then immediately detoxified in
liver.
In
adults primary metabolic pathway for paracetamol is glucoronidation. This
yields a relatively non-toxic metabolite which is excreted in bile and passed
out of the body.
A
small amount of drug is metabolized by CYP450 pathway (CYP3A4, CYP2E1) into
NAPQI which is extremely toxic to liver tissue as well as a strong biochemical
oxidizer.
In
an average adult only a small amount (appx. 10% of therapeutic dose) of NAPQI
produced which is inactivated by conjugation with glutathione. (At high dose
this enzyme get saturated and relative metabolite produce damaging effect on
hepatocytes)
Precaution:
1.
Though NH2 is more nucleophilic than OH excess acetic anhydride/acid chloride
should be avoided as there is a chance of double acetylation of 4-aminophenol.
2.
Avoid too high temperature.
STRUCTURAL ACTIVITY RELATIONSHIP (SAR):
1.
Presence of 1-4,di-substitution at
benzene is necessary for analgesic and antipyretic activity.
2.
Same functionalities at 1-2, or 1-3-position
if benzene destroy its activity.
3.
Conjugation in the system is
necessary for its activity.
4.
N-acetyl group increases the activity and
decreases the toxicity.
Posts
No comments:
Post a Comment