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Applied Chemstry Assignment 2 Kevin Doyle 19376213
Applied Chemstry Assignment 2 Kevin Doyle 19376213
Assignment 2
Applied Chemistry
Student No.19376213
Table of Contents
Assignment ...................................................................................................................... 3
Introduction ............................................................................................................................................ 3
Part 1 ................................................................................................................................................. 4
Part 2 ................................................................................................................................................. 4
Final process ........................................................................................................................................... 5
Conclusion ............................................................................................................................................... 6
References ....................................................................................................................... 7
Assignment
Introduction
Lidocaine is an amide local anaesthetic agent, and it was first developed in 1943 and 1946 by Nils
Löfgren and Bengt Lundquist. It was identified for its ability to act as a local anaesthetic that was less
addictive than cocaine and longer lasting than the preferred choice at the time of procaine
(Beecham, Nessel, & Goyal, 2024). It is now the most used local anaesthetic in the world.
the typical reaction scheme that is used to synthesize this chemical is as follows. 2,6-dimethylaniline
is reacted with chloroacetic acid chloride which gives rise to α-chloro-2,6-dimethylacetanilide. This is
then reacted further with dimethylamine to give the final compound of Lidocaine (Goodwin, 2009).
Part 2
The atom economy of step 1, 2 and, 3 are 88.36%, 87.4 and 84.37% for each of the steps individually
and the cumulative atom economy for the whole process is those values multiplied together and is
thus 65.16%.
The proposed new greener method of lidocaine synthesis adheres to many of the tenants of the 12
principles of green chemistry. Going through the choices and changes for each step-in comparison to
the typical reaction scheme we can see several connections.
For step 1 there are several choices that make the reaction in line with the 12 principles of green
chemistry. for example, instead of using a catalytic hydrogenation that would require high pressures
of hydrogen and an expensive potentially difficult to regenerate catalyst or a dissolved metal
reduction which would require harsh acids to break down the metals which would also bring its own
downsides a metal mediated reduction is used as they can be used with more benign proton sources
such as ionic liquids which further feeds into the green principals adhering to the 12th principle of
safety. Furthermore, the use of zinc as the metal of choice furthers the goal of a green process as it
adheres to the 4th principle of non-toxicity as zinc powder is less toxic than the equivalents
additionally the equivalents are more expensive than the choice of zinc thus adhering the process to
the 5th principle of minimisation. Additionally, the use of microwave irradiation for the activation
energy is part of the 6th principle of efficiency as microwave irradiation is typically far more efficient
that normal heating methods of convective heating typically used in experiments.
For the second step, the synthesis of α-chloro-2,6-dimethylacetanilide with the addition of
chloroacetic acid chloride to the synthesized 2,6-dimethylaniline. This process is closely linked to
several of the principles of green chemistry. Aligning with green chemistry principles such as 2. Atom
Economy, by incorporating all materials into the final product efficiently, and 8. Minimization, by
reducing the number of steps in the synthesis. This approach exemplifies 6. Efficiency, as it avoids
the need for additional activation steps, and touches on 3. Safety, balancing reactivity with safer
handling practices. Overall, this step reflects a streamlined, resource-efficient methodology
conducive to sustainable chemical practices.
Final process
The final process that I have designed will follow the system that I have outlined above using the
three steps that we have explored.
Step 1
Using the process outlined by Goodwin (2009) and the advised quantities it would be possible to first
make the 2,6-dimethylaniline using the following quantities and materials.
Material Quantity Units
Components
2-nitro-m-xylene 322.2900825 kg
zinc dust 278.7857717 kg
water 278.4676285 kg
diethylammonium formate 1574.379537 kg
Product
2,6-dimethylaniline 156.3082915 kg
Table 1: Step 1 components and products quantities
Step 2
Next the step would be to α-chloro-2,6-dimethylacetanilide and this would again follow the same
mechanism that is examined by Goodwin (2009) using this method and the following materials and
quantities it would be possible to make the required amount of α-chloro-2,6-dimethylacetanilide.
These are the following quantities of the components and the resulting products.
Material Quantity Units
Components
2,6-dimethylaniline 156.3082915 kg
chloroacetyl chloride 145.6796372 kg
Product
α-chloro-2,6-dimethylacetanilide 181.7855627 kg
Table 2: Step 2 components and products quantities
Step 2
The final step will be to use the scheme outlined again by Goodwin (2009) to finally synthesize the
lidocaine in the final reaction. The quantities needed have been listed below.
Material Quantity Units
Components
α-chloro-2,6-dimethylacetanilide 181.7855627 kg
Diethylamine 1008.989886 kg
Product
Lidocaine 100.0011522 kg
Table 3: Step 3 components and products quantities
Conclusion
The analysis explores the synthesis of Lidocaine, emphasizing the importance of environmentally
sustainable and safer chemical manufacturing practices. The traditional process, known for its
environmental drawbacks due to low conversion rates and hazardous material use, is reevaluated in
favour of greener methodologies. The paper suggests a revamped synthesis approach, adhering to
the 12 principles of green chemistry, involving non-traditional activation methods like microwave
irradiation and the elimination of harmful solvents. By modifying the initial steps from the reduction
of 2-nitro-m-xylene to the final production of Lidocaine, the proposed method enhances atom
economy and reduces toxic waste, offering a more sustainable, efficient, and safer alternative in
pharmaceutical manufacturing.
References
Beecham, G. B., Nessel, T. A., & Goyal, A. (2024). Lidocaine. In StatPearls [Internet]. Treasure
Island (FL): StatPearls Publishing. Retrieved from
https://www.ncbi.nlm.nih.gov/books/NBK539881/
Vardanyan, R.S., & Hruby, V.J. (2006). Local Anesthetics. In R.S. Vardanyan & V.J. Hruby (Eds.),
Synthesis of Essential Drugs (pp. 9-18). Elsevier. https://doi.org/10.1016/B978-044452166-
8/50002-9
Anastas, P. T., & Warner, J. C. (1998). Green Chemistry: Theory and Practice. Oxford University Press.
https://global.oup.com/academic/product/green-chemistry-theory-and-practice-
9780198506980?cc=ie&lang=en&
Schäfer, C., & Török, B. (2021). Application of nontraditional activation methods in green and
sustainable chemistry: Microwaves ultrasounds electro-photo- and mechanochemistry and
high hydrostatic pressure. In Nontraditional Activation Methods in Green and Sustainable
Applications (pp. 1-26). Elsevier. https://doi.org/10.1016/B978-0-12-819009-8.00016-5