ABSTRACT

Ibuprofen is well known as one of the Non-Steroid Anti-inflammatory Drugs

(NSAIDS) uses to treat inflammation such as inflammation of the joints or arthritis. Our aim

is to study and examine the structure of ibuprofen. In addition, we also want to discuss the

famous process to synthesis ibuprofen in chemical industry such as Boots Process and Green

process known as Hoechst process. In addition, we would study how different structure of

ibuprofen gives different effect on its reactivity. Also, not to forget the disadvantages of

ibuprofen as it gives harm on cardiovascular and pregnancy risks even it provide benefits.

Lastly, we will study the alternatives ways for replacing ibuprofen like turmeric.

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 1.0 INTRODUCTION

Isomer is an organic compound that has the same molecular formula but different

arrangements of atoms. There are two types of isomer; constitutional isomerism and

stereoisomerism. Constitutional isomerism is a molecule that has the same molecular formula

but has different structural formula. However, stereoisomerism is an isomer that has the same

structural formula but they have different spatial arrangements of their atoms. Enantiomers

and diastereoisomers are the categories of stereoisomerism.

Enantiomers are compounds which has molecules that are mirror images of one

another. Enantiomers are chiral in structure, non-superimposable, and induced optical

activity. The mixture of two enantiomers will form a racemic mixture; are optically inactive.

Why it is said that enantiomers are non-superimposable? It is because, no matter how we turn

these molecules, we cannot arrange them so that the atoms attached to central atom are

identically oriented in space. The objectives of this paper are to study the effect of the

structure of enantiomer on human, to detail out the reactivity of enantiomers, and to study the

structure of enantiomers.

The enantiomer that we are focusing in this paper is ibuprofen; one of the examples of

enantiomers in organic chemistry field that is most widely used as non-steroidal anti-

inflammatory drugs (NSAIDs). NSAIDs works by reducing hormones that causes

inflammation and pain in the body. Ibuprofen is used to reduce the pain and swelling

associated with arthritis by blocking the metabolism of arachidonic acid. It is also used to

reduce fever and treat pain or inflammation caused by many conditions such as headache,

toothache, back pain, arthritis, menstrual cramps, or minor injury. However, ibuprofen also

has its disadvantages.

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 2.0 CONTENT

2.0 CHARACTERISTICS OF IBUPROFEN

The chemical name of ibuprofen is (2RS)-2-[4-methylpropylphenyl]propanoic acid.

The molecular formula is C13H1802. The appearance of ibuprofen is colourless, crystalline

stable solid. It is readily soluble in most solvents insoluble in water, very soluble alcohol and

dissolves in dilute solutions of alkali hydroxides and carbonates.

2.1 STRUCTURE OF IBUPROFEN

Ibuprofen can exist as a pair of optical isomers that are mirror images of each other.

These mirror images are non-superimposable; they are like a pair of hand - left and right

hands are mirror images but not identical. This mirror image property occurs in molecules

that have a carbon atom that bonded to four different groups. The two optical isomers of

ibuprofen are identified by the prefixes R and S+ (see figure 1)

Figure 1

Mirror image isomers are identical in many properties such as solubility, melting

point and boiling point. They can be distinguished by the rotation of the plane polarized light.

They rotate the plane polarized light in different directions: the + ve isomer clockwise and the

ve isomer anticlockwise. The symbols R and S refer to the 3D arrangement of the atoms in

space. The two isomers however, behave differently when they interact with other handed

molecules such as the prostaglandins. One of the two optical isomers of ibuprofen; the S+

form, inhibits prostaglandin synthesis while the R form has no anti-inflammatory effect.

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 However, it has been found that there is an enzyme in the body that converts the R

form into the S+. In fact 60% of the R form is converted into S+. This means that in a

typical dose of ibuprofen of 400 mg, 200 mg is S+ and 200 mg R. Of the 200 mg of R,

60% (i.e. 120 mg) is converted into the active R+ form, giving a total of active form of 320

mg. Therefore there is little point in going to the trouble of synthesising the S+ form only,

and ibuprofen is sold as a racemic mixture (one initially containing equal amounts of both

optical isomers). However a stereospecific synthesis is possible. Figure 2 shows the structure

of ibuprofen.

Figure 2

2.2 MECHANISM ON SYNTHESIZING IBUPROFEN

According to RSC Organization, there are two most popular methods for synthetizing

ibuprofen. One of it is Boots process and the other one is Hoechst. Precursor of synthetizing

in both methods begin with the compound 2-methylpropylbenzene (Figure 3).

Figure 3

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 For Boots process, it require six steps, it begins when 2-methylpropylbenzene

reacts with ethanoic anhydride to form isobutyl benzene in the present of aluminium chloride.

Then, the reaction followed by Friedel-Crafts acetylation of isobutylbenzene. Next, the

Darzens reaction was used to give , -epoxy ester which was then hydrolyzed and

decarboxylated to the aldehyde. Interaction with hydroxylamine then gave an oxime which

can be converted to nitrile and hydrolyzed to the carboxylic acid (Figure 4).

this process had an overall atom efficiency of just 40% of the mass of all the

atoms going into the process, 60% ended up in waste products.

The Boots synthesis has been replaced by the new, known as Hoechst process,

more efficient synthesis shown in Figure 5. It starts with the same compound but has fewer

steps which they increase the efficiency of product and shorting the catalytic process by 3

steps. It is also has been described as the green synthesis.

2.3 COMPARATIVE PHARMACOLOGY OF S (+)-IBUPROFEN AND (RS)-IBUPROFEN

Racemic ibuprofen, which contains equal quantities of R (-)-ibuprofen and S (+)-

ibuprofen, has been used as an anti-inflammatory and analgesic agent for over 30 years.

Although the S (+)-enantiomer is capable of inhibiting cyclooxygenase (COX) at clinically

relevant concentrations, R (-)-ibuprofen is not a COX inhibitor.

The two enantiomers of ibuprofen are therefore different in terms of their

pharmacological properties and may be regarded as two different 'drugs'. They also differ in

terms of their metabolic profiles.

For example, R (-)-ibuprofen becomes involved in pathways of lipid metabolism and is

incorporated into triglycerides along with endogenous fatty acids. S (+)-Ibuprofen does not

appear to become involved in these unusual metabolic reactions, which is why S (+)-

ibuprofen is regarded as being metabolically 'cleaner'.

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 When racemic ibuprofen is given to humans, a substantial fraction of the dose of R (-)-

ibuprofen (50%-60%) undergoes 'metabolic inversion' to yield S (+)-ibuprofen. On this basis,

it has been argued that to obtain clinical effects that are comparable to those of a given dose

of racemic ibuprofen, the dose of S (+)-ibuprofen would need to be about 75% of the dose of

the racemate.

Recent studies have demonstrated that the clinical benefits of racemic ibuprofen can

be derived from the administration of the single S (+)-enantiomer at a dose that is half that of

the racemate. For example, 200 mg of S (+)-ibuprofen has been found to be superior or at

least equivalent to 400 mg of the racemate in the relief of dental pain. Possible explanations

for this higher than expected efficacy of S (+)-ibuprofen are considered.

2.4 MECHANISM OF ACTION OF IBUPROFEN

Ibuprofen is a non-selective inhibitor of an enzyme called cyclooxygenase (COX),

which is required for the synthesis of prostaglandins via the arachidonic acid pathway. COX

is needed to convert arachidonic acid to prostaglandin H2 (PGH2) in the body. This PGH2 is

then converted to prostaglandins. The inhibition of COX by ibuprofen therefore lowers the

level of prostaglandins made by the body. Prostaglandins are sometimes referred to as local

mediators because they carry out important functions near to where they were produced,

rather than throughout the body

The prostaglandins that are formed from PGH2 are important mediators of sensations

such as pain and processes such as fever and inflammation. The antipyretic effects may arise

as a result of action on the hypothalamus leading to vasodilation, an increased peripheral

blood flow and subsequent heat dissipation.

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 Anticoagulant effects are also mediated through inhibition of COX, which converts

arachidonic acid into thromboxane A2, a vital component in platelet aggregation that leads to

the formation of blood clots.

There are two forms of COX in the body - COX-1 and COX-2. The pain and

inflammation reducing effects of NSAIDs are mediated through the inhibition of COX-2,

while COX-1 inhibition blocks the formation of thromboxane. The long-term blockage of

COX-1 with chronic use of NSAID, however, may cause gastric toxicity, as COX-1 usually

maintains the gastric mucosa. The mechanism of action of ibuprofen can be referred in figure

6.

2.5 ADVANTAGES AND DISADVANTAGES OF IBUPROFEN

As we all know, some of substances or chemical have advantages and disadvantages.

Same goes to the ibuprofen as it also has its own benefits and bad effects on the patients

when they consume this kind of medicine. The benefits of ibuprofen are decreases

inflammation, believed to slow down progression of Alzheimers, more efficient than other

NSAIDs, non-addictive and also relatively cheap. The common use of ibuprofen to decrease

inflammation is for rheumatoid arthritis. This drug can reduce some of the pain and swelling

but it will not alter the course of the disease.

Ibuprofen has been found to slow down the progression of Alzheimers

disease. Ibuprofen is thought to be able to reduce the amounts of beta-amyloid (a protein

fragment whose accumulation is linked to the disease) that buildup in the brain while this

information supports previous data which indicates that ibuprofen and other NSAIDs can

slow down or prevent the onset of Alzheimers disease, scientists say it may also introduce a

new way of thinking about how ibuprofen protects the brain. About 20 studies carried out on

people have shown that those who took NSAIDs for various reasons had a much lower risk of

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developing Alzheimers disease than those people who did not take NSAIDs. Evidence has

shown that inflammation in the brain, prompted by amyloid deposits, activates immune cells

and elicits harmful substances that destroy nerve cells. Ibuprofen is thought to interrupt this

pathway of events (David P. Wolfe, 2013).

Besides helping the patients,the ibuprofen also has the side effects on it. One of it is

high potential for drug interactions. For example, people who want to take ibuprofen for

arthritis should seek advice from their doctor. Ibuprofen may also cause life-threatening heart

or circulation problems such as heart attack or stroke, especially if it is use in long term.

Next, someone who is in possession of ibuprofen may experience nausea, vomiting or

diarrhoea. On the other hand, consuming ibuprofen in a large dose will highly increase the

risk of stroke and heart attack due to the blockage of blood supply to the brain and heart.

Furthermore, this medicine may also cause serious effects on the stomach or intestines,

including bleeding or perforation (forming of a hole). These conditions can be fatal and can

occur without warning while you are taking ibuprofen, especially in older adults.

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 CONCLUSION

As a conclusion, we can identify that enantiomers are the two identical molecules but

in different arrangement. Thus, it is cannot be superimposed on each other, which it will

gives different molecule when one is placed on another. The molecule also mirror to each

other.

An example of enantiomers that has been discussed is ibuprofen. The ibuprofen is very

dangerous and will give harm if people taking it in improper way and they will get variety of

diseases that can effect life. So, it has to be taken in the right amount and following the

experts instructions.

In order to avoid from any disease to occurred, there are lot of suggestion that can

applied from now until the future. Firstly, do not use ibuprofen if you have ever had an

allergic reaction to any other pain reliever/fever reducer. Secondly, ask doctor or pharmacist

before use if you are taking other drug. Thirdly, when using this product take with food or

milk if stomach upset occurs. And lastly, if pregnant or breast-feeding, ask a health

professional before use. It is especially important not to use ibuprofen during the last 3

months of pregnancy unless definitely directed to do so by a doctor because it may cause

problems in the unborn child or complications during delivery.

Moreover turmeric that known as curcumin also can be used as a painkiller that works

same likes ibuprofen. It will block the protein that causes inflammation and stopping the

sending of the neurotransmitter caller P which send the message to the brain. Studies show

that curcumin is effective in easing the chronic pain of rheumatoid arthritis.

As we had discussed earlier, enantiomers have the same structural formula but their

reactivity is different from one another. As in Ibuprofen, one enantiomer will give benefit to

human. In the other hand, the other one giving neither any effect nor harm. This is the same

as human. Allah creates human with a similar structure; have eyes, nose, mouth, and other

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parts of body. However, not all human have the same characteristics, in terms of their moral,

ethics, and reaction to something. Allah had given human aql to think whether we want to do

good things or bad things. As we are indebted to Allah for giving us lives, creating us, giving

free oxygen for us to breathe in. We had to be grateful to Allah. The only best solution to

settle the debts unto Allah is through total submission to His Commandments and abstention

from His Prohibitions (the dos and donts). In fact, mans submission is a manifestation of

his inclination to God.

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