Vol. 21 No. 1 (2022): Mapana Journal of Sciences
Research Articles

A Systematic Study towards the Synthesis, Isolation, and Recrystallization of Atovaquone, an Antimalarial Drug: A Sustainable Synthetic Pathway

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  • Sanjay Sukumar Saralaya,
  • Shashiprabha,
  • Shridhara Kanakamajalu,
  • Kuppuswamy Nagarajan,
  • Koottungalmadhom Ramaswamy Ranganathan
Sanjay Sukumar Saralaya
SDM Institute of Technology, Ujire.
Bio
Shashiprabha
SDM College (Autonomous), Ujire.
Bio
Shridhara Kanakamajalu
ArkGen Pharma Private Limited, Bangalore.
Bio
Kuppuswamy Nagarajan
Retired Consultant for Alkem Labs and KOP Research Centre, Bangalore.
Bio
Koottungalmadhom Ramaswamy Ranganathan
Retired Head of R & D, Alkem Labs and KOP Research Centre, Bangalore.
Bio
DOI: https://doi.org/10.12723/mjs.60.2

Published 2022-07-28

Keywords

  • 2-[trans-4-(4-chlorophenyl) cyclohexyl]-3-hydroxy-1,
  • 4-naphthoquinone(Atovaquone),
  • reaction optimization,
  • isolation,
  • recrystallization

Copyright (c) 2022

Creative Commons License

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Abstract

In the present work, studies were conducted towards the synthesis of 2-[trans-4-(4-chlorophenyl) cyclohexyl]-3-hydroxy-1 ,4-naphthoquinone 5 with systematic reaction and recrystallization condition optimization to isolate 5 in high yield with better purity. Synthesis of 5 was done by the hydrolysis of 2-[trans-4-(4-chlorophenyl) cyclohexyl]-3-chloro-1, 4-naphthoquinone 4, which was isolated by the decarboxylative condensation of trans-4-(4-chlorophenyl) cyclohexanecarboxylic acid 3 with naphthoquinone moiety. After the hydrolysis of 4, isolation of crude 5 was done by the use of acetic acid instead of dilute hydrochloric acid, product 5 was isolated in good purity with very less polar impurities. The study extends to provide the polymorphic form I of 5 by the use
of solvent combination for the recrystallization, prior art
reports the use of a large volume of solvent for the
isolation of polymorphic form I of 5. The use of a large
volume of solvent becomes a bottleneck for the
commercial synthesis of 5.

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