synthesis: aspirin & paracetamol

Organic synthesis or synthetic chemistry

Art and science of constructing prganic molecules, whose primary element is carbon, such as those found in living creatures and some synthetic materials

A multi-step synthesis of any organic cmpd requires the chemist to accomplish related tasks

-constructing the carbon framework or skeleton of the desired molecule
-introducing, removing, pr transforming the functional groups in a fashion that achieves the functionality of the desired compound
-exercising selective stereo-control at all stages in which centers of stereoisomerism are created or influenced
-since a successful synthesis must produce the desired product in reasonable amount, it should be as short and efficient as possible
-the format of synthesis is important
-if numerous functional groups are present at intermediate stage, some of these may require protection from unwanted reaction
-the starting cmpd and reagents for a synthesis must be purchased, so economic considerations are often significant
-for a given target molecule, several different reaction sequence may serve to accomplish its synthesis

Importance of organic synthesis

-drug discovery
-materials science
-agriculture

Drug discovery

vital for pharmaceuticals to develop new medicines

Material science

Used in the creation of advance materials

Agriculture

Plays a role in developing new crop protection prod

Challenges in organic synthesis

-selectivity
-yield
-efficiency

Selectivity

Ensuring rxns produce the desired product

Yield

Maximizing the amount of product obtained

Efficiency

Minimizing resources and time consumption

Aspirin
Molecular formula

C9H8O4

Aspirin
Synonyms: iupac

2-acetoxybenzoic acid

Aspirin
Synonyms

Acetylsalicylic acid, ASA

Aspirin
Molecular weight

180.16 g/mol

Aspirin

an odorless, white crystalline powder chemically known as 2-acetoxybenzoic acid or acetylsalicylic acid (ASA)

Aspirin

a weak acid that is only slightly soluble in water, and slightly bitter taste

Aspirin

an aromatic cmpd with carboxylic acid and ester functional grp

Aspirin

A known analgesic, antipyretic, anti-inflammatory and antiplatelet drug

Aspirin solubility

0.25g per 100 mL in water at 15 C

Aspirin density

1.40 g/cm3

Aspirin chemical safety

Irritant

Aspirin stability

gradually hydrolyzes into salicylic acid and acetic acid upon exposure to moisture in air

Aspirin structure

Benzene with an attached carboxyl group and ester grp on ortho position

Aspirin is widely used for its analgesic, antipyretic and anti-inflammatory properties. It works by __

inhibiting the enzyme cyclooxegenase (COX)

Cyclooxygenase (COX) is involved in the __

Biosynthesis of prostaglandins

Prostaglandins

Compounds that mediate inflammation, pain and fever

By inhibiting COX, aspirin reduces the __

production of these mediators thereby alleviating the symptoms

In addition to its common uses, aspirin has been found to have __

antiplatelet effects

In addition to its common uses, aspirin has been found to have antiplatelet effects, making it valuable in the __

Prevention of cardiovascular events such as heart attack or stroke

Low dose aspirin therapy

often prescribed for individuals at risk of heart attack and stroke, as it helps prevent formation of blood clot

Aspirin
Type of rxn involved

Acetylation (esterification) of salicylic acid with acetic acid

Aspirin absorption

Rapidly metabolized from the GIT, with peak plasma concentrations typically occurring within 30 mins-2hrs post administration

Aspirin distribution

Aspirin and its primary metabolite, salicylic acid, are widely distributed throughout the body

Aspirin distribution
Salicylic acid

is extensively bound to plasma proteins, which can affect its pharmacokinetics and interaction with other drugs

Aspirin metabolism

After absorption, aspirin is hydrolyzed into salicylic acid in the liver

Aspirin metabolism
Salicylic acid undergoes further metabolism through __

Conjugatiin with glycine or glucuronic acid

Aspirin excretion

The metabolites of aspirin are excreted primarily via the kidneys.

Aspirin excretion
The elimination half life of salicylic acid is __

Dose dependent ranging from 2-19 hrs, depending on the administered dose and individual metabolic variations

Salicylic acid mol formula

C7H6O3

Salicylic acid mol wt

138 g/mole

Acetic anhydride mol wht

102 g/ mole

Melting pt of aspirin

135 C

The actual mp if aspirin may be lower due to

Presence of impurities in the aspirin crystals

Paracetamol mol formula

C8H9NO2

Paracetamol iupac

N-(4-hydroxyphenyl)ethanamide

Paracetamol synonym

acetaminophen

Paracetamol mol wt

151.16 g/mol

Paracetamol

Odorless white crystalline solid
Bitter taste

Paracetamol pH

(Sat aq soln) about 6

Acetaminophen (paracetamol) aka

Tylenol

Paracetamol is the most commonly taken__

analgesic worldwide

Paracetamol is the recommended ___

First line therapy in pain conditions by the who

Paracetamol is also used for its antipyretic affects

Helping to reduce fever

Paracetamol was initially approved by the US FDA in 1951 and is available in a variety of forms including:

-syrup form
-regular tablets
-effervescent tablets
-injection
-suppository

Acetaminophen is often found combined with other drugs in more than 600 otc __

-allergy medications
-cold medications
-sleep medications
-pain relievers
-and other products

Paracetamol type of rxn involved

Nucleophilic addition and acylation

Paracetamol absorption

Rapidly absorbed from the GIT, with peak plasma concentrations typically reached within 30 minutes to 2 hours after oral administration

Paracetamol distribution

Once absorbed, it is widely distributed throughout the body

Paracetamol metabolism

Primarily metabolized in the liver

Paracetamol metabolism
Undergoes conjugation with __

glucuronic acid and sulfuric acid

Paracetamol metabolism
A small fraction of the drug is metabolized by the __

CYP 450 enzyme system to form a reactive metabolite, N-acetyl-p-benzoquinone imine

Under normal conditions, NAPQI is detoxified by __

Conjugation with glutathione

In cases of paracetamol overdose

The capacity of the detoxification pathway can be overwhelmed leading to hepatotoxicity

Paracetamol excretion

The metabolites of paracetamol are excreted primarily via the kidneys.

Paracetamol excretion
The elimination half life of paracetamol is __

Generally 1.5 to 3 hrs in healthy individuals

P aminophenol mol formula

C6H7NO

P amino mol wt

109

Acetic anhydride mol formula

C4H6O3

Paracetamol mp

169-170 C