The bar chart illustrates the sales of properties from 2009 to 2011.

The properties
includes apartment, condominium, single storey house and double storey house. Overall,
condominium, single storey house and double storey house showed an upward trend
throughout the period whereas the apartment showed a downward trend throughout the
period. Both sales of single storey house and double storey house had some fluctuation.
Although these both properties initially experienced an increase from 2009 to 2010,
however, the sales for both of them showed a slight decrease from 2010 to 2011.

The sales of apartment declined gradually throughout the period which in contrast
to the sales of condominium increase gradually throughout the period. In 2009, the
apartment’s sales showed the highest sales among others by achieving 100,000 units.
However, it showed the lowest sales in 2011 which is 50,000. In contrast, the condominium
showed the lowest sales in 2009 by 20,000 and the highest sales in 2011 by hitting 200,000.
Even both single storey house and double storey house showed the same trend, double
storey house able to reach the highest sales in 2010 by reaching 180,000.

In a nutshell, the total sales for all the properties showed an upward trend from
2009 to 2011.

1.1 Raw materials for the Production of Ibuprofen

The traditional commercial manufacture of ibuprofen was developed by the Boots

Company of England in 1960s. The Boot’s method of synthesising ibuprofen started
by using the compound of 2-methylpropylbenzene which can be made from
compounds separated from crude oil.

2-methylpropylbenzene
Diagram 1.1: raw material of Ibuprofen

1.2 Chemical Reactions involved for the Production of Ibuprofen

The traditional Boot’s method of synthesising Ibuprofen has been modified by the
engineers evolving through the decades to minimize the by-products produced from
the reactions and eventually results in a few effective alternating reaction pathways to
produce Ibuprofen. For instance, the green synthesis BHC pathway and Continuous
Photochemistry via photo-Favorskii by McQuade’s group which further modified by
Jamison’s group in order to increase the products yield.

In 1960s, the Boot’s method of synthesising ibuprofen is a six steps process

and eventually leaving a large quantities of unwanted waste chemical by-products
which must be disposed of. The reaction mechanism of Boot’s method of synthesis of
Ibuprofen has shown below:
 Diagram 1.2.1: Boot’s synthesis of Ibuprofen

The Boot’s method of the preparation of Ibuprofen starts by using the raw
material isobutylbenzene and undergoing Friedel-crafts acylation reaction.
Isobutylbenzene reacts with acetic with the presence of aluminium trichloride to
produce 1-(4-(2-Methylproplyl)phenyl)ethane-1-one. Then, 1-(4-(2-
Methylproplyl)phenyl)ethane-1-one undergoing Darzens Condensation by reacting
with the α-chloroester which have been treated with sodium ethoxide base to yield the
α, β-epoxy ester.
In addition, it will undergoes glycidic acid rearrangement by rearranging the
ester from previous steps with aqueous acid into carbon skeleton to yield aldehyde
compound. The aldehyde is then undergoes oxime formation by reacting with
hydroxylamine to convert into oxime. The oxime further undergoes the nitrile
formation to form nitrile compound by losing water.
Lastly, the nitrile will undergoes nitrile hydrolysis reaction slowly to yield
Ibuprofen. According to the atom economy calculation, the production yields of
Ibuprofen synthesised by Boot’s method is only 40% which means there is more than
half the materials used in the synthesis are wasted.
However, a new company called BHC, was formed and developed a new
‘green’ commercial synthesis of ibuprofen. This consortium developed an alternative
synthesis of ibuprofen from the same starting materials with only three steps:

Diagram 1.2.2: Green synthesis of Ibuprofen

 First and foremost, the isobutylbenzene reacts with acetic anhydride with the
presence of the anhydrous HF solvent as catalyst to produce 4-Isobutylacetophenone
by undergoing Friedel-Crafts acylation. The anhydrous HF catalysts are recovered
and recycled with efficiency greater than 99.9%. The desired conditions for this
reaction are 80°C and 0.7MPa and 3 hours duration.
Further, the 4-Isobutylacetophenone reacts with hydrogen with the presence of
hydrogen catalysts to yield 1-(4-isobutylphenyl) ethanol and the by-products are p-
isobutylstyrene and p-isobutylethylbenzene. This reaction involves three phases
which are Gas-Liquid-Solid.Palladium or Raney Nickel act as catalysts as they are
insoluble that can be recovered and reused. Hydrogenation is a solvent-free process,
simplifying product recovery and minimizing the emissions.The optimum conditions
for this reaction are temperature of 300K-400K and pressure of 0.6-6.5MPa.
Lastly, the 1-(4-isobutylphenyl) ethanol undergoes carbonylation to produce
Ibuprofen with the presence of catalyst (PdCl2) or MEK solvent which increases the
rate of reaction. This reaction takes three phase reaction which is Gas-Liquid-Liquid
and it is also a solvent-free reaction. It will takes place above the melting point of the
organic compounds. The optimum condition of carbonylation including the
temperature which should be maintaining around 110-140 C and the pressure should
be maintaining at 5-16.5MPa.
By virtue of only requiring three steps, the green synthesis offering the
benefits of a greater throughput compared with the six steps traditional Ibuprofen
synthesis. This translate into the ability to produce a larger quantities of Ibuprofen
with less time and with less capital expenditure, resulting in significant economic
benefits to the company which providing a win-win situation for the company and the
environment. The new process for the production of ibuprofen became a model for
environmental excellence in chemical technology, and BHC received the Kirkpatrick
Achievement Award for “outstanding advances in chemical engineering technology”
in 1993 and the US Presidential Green Chemistry Award in 1997. The BHC ibuprofen
is an innovative, efficient technology that has revolutionized bulk pharmaceutical.
The percentage atom economy for green synthesis of Ibuprofen is 77% which is
double for the Boot’s synthesis of Ibuprofen.

References
https://www.researchgate.net/profile/Jorge_Ibanez4/publication/315525104/figure/fig
2/AS:478016288628737@1490979372609/Conventional-synthesis-of-
ibuprofen_W640.jpg

http://www.scheikundeinbedrijf.nl/content/Modules/Modulenaam/Files/case.pdf

https://www.molport.com/shop/moleculelink/2-methylpropyl-benzene/1762123