TABLE OF CONTENT

ABSTRACT............................................................................................................................................ 2
1.0 INTRODUCTION ...................................................................................................................... 3
2.0 CONTENT .................................................................................................................................. 5
2.1 STRUCTURE OF IBUPROFEN ............................................................................................ 5
2.2 SYNTHESIS OF IBUPROFEN .............................................................................................. 5
2.3 PHYSICOCHEMICAL PROPERTIES OF IBUPROFEN ..................................................... 8
2.4 ADVANTAGES AND DISADVANTAGES OF IBUPROFEN ............................................ 9
3.0 CONCLUSION ......................................................................................................................... 11
APPENDIX ........................................................................................................................................... 13
REFERENCES ..................................................................................................................................... 14
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. This

study is interested to expose and examine the structure of ibuprofen for instance the types of

functional group for ibuprofen. In addition, we also want to discuss the famous process to

synthesis ibuprofen in chemical industry such as Boots Process and Green Process (Martyn

Poliakoff & Pete Licence, 2007). On the other hand, we also want to highlight the

physicochemical properties of ibuprofen such as boiling point and melting point of ibuprofen,

solubility of ibuprofen as well as form of ibuprofen either R or S forms. Nevertheless, we

also emphasize the advantages of ibuprofen like its effectiveness in slowing the progression

of Alzheimer and comparison to other NSAIDS drugs and not to forget the disadvantages of

ibuprofen such as complication after interaction with other medicine. Lastly, we will study

the alternatives ways to for replacing ibuprofen like Boswellia and turmeric.

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

arrangement of atom. There are two types of isomerism which are Constitional isomerism

and Stereoisomerism. Stereomerism then subdivided into two types of isomerism which are

cis transisomerism and optical isomerism (Tan Y.T,2014). Optical isomerism is observed

when a solution has the ability to rotate plane polarized light and is called optically active.

The basic principle for optically active is chiral carbon. Chiral centers or chiral atom are

tetrahedral atoms (usually carbons) that attach to four different substituents. Molecules with

more than one chiral center are usually chiral. Chiral carbon atom also known as asymmetric

carbon atom and often shown as C*.Molecule that contains chiral carbon would have mirror

image that cannot be superimposed on it, means that the image does not show the same

structureIn perspective of optical isomerism,scientists have divided into two subdivisions of

optical ismoerism:

1) Enantiomers(mirror image)
2) Disastereomers(non mirror image)

Enantiomers are chiral molecules that are mirror images of one another. Furthermore,

the molecules are non-superimposable on one another. This means that the molecules cannot

be placed on top of one another and give the same molecule. Chiral molecules with one or

more stereocenters can be enantiomers. It is sometimes difficult to determine whether or not

two molecules are enantiomers.Here is the example of enantiomer, figure 1 :

Figure 1: Lactic acid

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 One of the common examples of enantiomers in chemistry term is ibuprofen.

Ibuprofen is the most widely used as non-steroidal anti-inflammatory drugs (NSAIDs) (Jenny

Bryan, 2009). NSAIDs are the first choice of drugs that are normally used for the treatment of

pain and inflammation. Ibuprofen is used to reduce the pain and swelling associated with

arthritis by blocking the metabolism of arachidonic acid by cyclooxygenase enzyme (COX)

thereby the production of prostaglandin. It is also used to relieve the symptoms of a wide

range of illnesses such as headaches, backache, period pain, dental pain, neuralgia, rheumatic

pain, muscular pain, migraine, cold and flu symptoms and arthritis. The aims and objectives

of this project are to emphasize how ibuprofen is synthetized, physiochemical of ibuprofen as

well as advantages and disadvantages of ibuprofen.

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2.0 CONTENT

2.1 STRUCTURE OF IBUPROFEN

Figure 2 below shows the structure of ibuprofen. Ibuprofen consists of two functional

groups which are carboxylic group and phenyl group. Ibuprofen has a particularly interesting

property as it can exist as a pair of optical isomers that are mirror images of each other. These

mirror images are non-superimposable, as they are like a pair of shoes, left and right shoes

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

a carbon atom to which four different groups are bonded.

Figure 2: Ibuprofen

2.2 SYNTHESIS OF IBUPROFEN

Synthetizing of ibuprofen was commenced in 1960 by the pharmaceutical company

Boot (England) and sold under the commercial name such as Advil and Motrin (retrieve from

http://www2.epa.gov/green-chemistry/1997-greener-synthetic-pathways-award). There are

two most popular methods for synthetizing ibuprofen. One of it is Boots process and the other

one is Hoechst process (A. Ahmadi et al, 2014). Precursor of synthetizing in both methods

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

Figure 3: 2-methylprophylbenzene

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 Boots method or route consists of six steps. The process of ibuprofen 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).

Figure 4: Boots process steps

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 According to BHC, 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 (Martyn

Poliakoff & Pete Licence, 2007). However, in 1990, BHC had found a new process in which

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

approximately 80 % atom utilization virtually 99% including the recovered by-product acetic

acid (Martyn Poliakoff & Pete Licence, 2007).In 1996, BHC won Presidential Green

Chemistry Challenge Award and this process is called Hoechst process or green synthesis

(Peter J. Dunn et al, 2010). The sequences of the process as followed (Figure 5):

Figure 3: Green Process

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In Hoechst process, Raney Nickel catalyst is used instead of aluminium chloride. This is

because Raney Nickel can be recycled and reused. The energy used during these steps also

significantly reduces compare to Boots process.

2.3 PHYSICOCHEMICAL PROPERTIES OF IBUPROFEN

The physicochemical (physical and chemical) properties of ibuprofen are so important

for every pharmacist before they take an action to produce it in the large scales, in order to

make the drug more secure and harmless for those who consume the chemical substances.

As mention before, Ibuprofen, 2-(4-isobutylphenyl)-propionic acid, non-streroidal

drug is widely been used throughout the world as anti-inflammatory analgesic or as a

painkiller is practically insoluble in water, but very soluble in most organic solvents. It has

compaction characteristics owing to its needle-like (acicular) crystalline structure and

viscoelastic properties. Chemically, Ibuprofen is a colourless drug. The melting point and

boiling point of ibuprofen is 77-78C and 158C, respectively.

Figure 6: S and R form of ibuprofen

In addition, it is an optically active compound with both S and R-isomers (Figure 6),

of which the S (dextrorotatory) isomer is the more biologically active, this isomer has also

been isolated and used medically. Ibuprofen has been produced as a racemate. It contains

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chiral center in the -position of the functional group of propionate. Ibuprofen works by

inhibiting the activity of class enzymes called cyclooxygenases (COX). Both type of drugs,

Ibuprofen and Aspirin inhibit COX, but they do in the different ways. Ibuprofen binds non-

covalently to a COX enzyme by reversible inhibition while, aspirin forms a covalent bond to

a serine residue in the enzyme. The bond cannot be broken called as irreversible inhibition.

Moreover, ibuprofen is stable, combustible and incompatible with strong oxidizing agents.

2.4 ADVANTAGES AND DISADVANTAGES OF IBUPROFEN

As we all know about human creature, some of their creations 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

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

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

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

Ibuprofen is much more effective than aspirin. To achieve the same anti-

inflammatory effect 4000mg of aspirin needs to be administered while only 2400mg must be

used in the case of ibuprofen. This again shows that ibuprofen is more useful than other

drugs, as because it is present at lower concentrations in the body the chance of unwanted

side effects are much less. Ibuprofen is not addictive and so will not cause problems with

people becoming dependent on it, this can occur with other painkillers. It also means that

people will not build up a tolerance to the drug: meaning that they will not need larger and

larger quantities of the drug to induce the same pain releasing effects. Ibuprofen is a

relatively cheap drug and does not require a prescription and so is widely available. It is mild

enough to not need a prescription but at the same time efficient in its action.

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. A doctor will be able to inform his patient of

any ibuprofen interactions with other medications. For example, ibuprofen is also a blood

thinner and it should not be taken along with other blood thinners, since this can cause

bleeding or clotting problems. Doctors may also be able to treat any underlying causes of

arthritis. 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.

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3.0 CONCLUSION
There are many reasons why patients should avoid taking ibuprofen to decrease the

level of pain that they had. Just because of many dangers may come after using

ibuprofen,leads to seek for the alternative ways that may prevent from the side

effects.Boswellia is known as Indian frankincense. This anti-inflammatory remedy comes

from the Boswell Serrata tree which grows in India and has been used in Ayurvedic medicine

(ancient traditional medicine among Indian native) for centuries. Traditionally, it has been

used in resin format to treat chronic inflammatory conditions, as well as a number of other

disorders including osteoarthritis, asthma and rheumatoid arthritis. The anti-inflammatory of

boswellia contains boswellic acids in which these acids increase blood flow to the joints and

prevent inflammatory by blocking the entering of white cells to damaged tissue. Usually, a

suggested dose is 450 to 750 mg daily for three to four weeks. In one study, this decreased

arthritis pain by over 80% by consuming 900-1,000 mg a day. (Retrieve from

http://www.undergroundhealth.com/9-natural-alternatives-to-ibuprofen-and-nsaids-with-no-

side-effects)

In addition, turmeric herbs also known as curcumin is another alternatives besides

ibuprofen by acting as a potent painkiller that blocking the protein that cause inflammatation

and stoping 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

(Retrieve from http://www.undergroundhealth.com/9-natural-alternatives-to-ibuprofen-and-

nsaids-with-no-side-effects). A suggested dose is 400 to 600 mg of curcumin taken three

times daily for pain and inflammation.

Islam teaches us something that we should realize. How we take care ourselves, how

we manage to cure the diseases. Yes that might be ignored by certain people, because they

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dont realize that Allah sent down Al-Quran as the book of medical, the book of miracle and

so on.

.... and We have sent down to thee the Book explaining all things, a Guide, a Mercy, and Glad

Tidings to Muslims. [Surah An-Nahl: verses 89]

That is how we should always appreciate the valuable things sent down for us. By

following his guidance through His revelation (Al-Quran). In the modern world, the

technology has created many kinds of drugs. In order to save the people of the earth,

ibuprofen could decrease the level of pain in patients and could leads to another negative

compilations as mention before. By the way, as a true Muslims, Allah is our hopes. He is the

one that could cure us. Prophet Ayyub was attacked by diseases during that time but he never

despairs on Allah. In the holy Quran, chapter Sad verses 41-42, the story prophet Ayyub

asked for Allahs cure and he at the same time tried to do a treatment by Strike [the ground]

with his foot; this is a [spring for] a cool bath and drink. It is similar for our condition, try our

best to create the best medicine for human sake.

.And when you have decided, then rely upon Allah . Indeed, Allah loves those who rely [upon

Him]. [Surah Ali-Imran verses 159]

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APPENDIX

Brand of ibuprofen

Turmeric Herb

Boswellia

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