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To improve the yield of Atovaquone, we explored the chemical consequences occurring during its step-wise synthesis (process chemistry). Hence, the entire focus of this initiative was aimed towards the isolation of a few major process origin byproducts that were formed during the two-step reaction process. The synthesis of Atovaquone was done by the use of commercially viable key starting material frans-4-(4-chlorophenyl) cyclohexanecarboxylic acid for the decarboxylative coupling reaction with another key reactant 2,3-dichloro-l,4-naphthoquinone to obtain the intermediate. The isolated intermediate was hydrolyzed to obtain Atovaquone. From the mother liquors (MLRs) of each stage, we were able to isolate a few major process origin impurities and characterize them with the assistance of spectral data. Additionally, we had even synthesized some of the impurities and compared them with the ones that are isolated from the MLRs. In this work, we report the experimental aspects and results related to six process-origin impurities of Atovaquone. Too many impurities/byproducts are formed during the process, which substantiates for the moderate yield of the disclosed synthetic route to isolate Atovaquone. Isolation and characterization of all impurities formed will be an uphill task. Still, it will undoubtedly contribute to ascertaining the mass balance of the synthetic route under focus to get Atovaquone. [ABSTRACT FROM AUTHOR]

Buparvaquone 1a is a predominant anti-protozoal drug, it belongs to the pharmacologically active class of hydroxynaphthoquinones. There are numerous publications on the wide therapeutic applications of 1a, but only a few approaches were reported towards its synthesis. Most of the prior arts report the synthesis from expensive raw materials with low yield, whereas only a few involves the use of readily available and less expensive raw materials with moderate to better yield. The present review work covers the developments on therapeutic applications of 1a along with the synthetic approaches disclosed till date. [ABSTRACT FROM AUTHOR]

Present work reports a novel and commercially viable method for the synthesis of 2-chloro-3-[trans-4-(4-chlorophenyl)cyclohexyl]-1,4-naphthoquinone1, a renowned intermediate of Atovaquone (an antimalarial drug). The majority of the prior arts disclose the synthesis of this intermediate from the expensive starting material 2-chloro-1,4-naphthoquinone2, in relatively low yield. In this regard, it was considered worthwhile to synthesize 1 by a novel route using cheaper starting material 2,3-dichloro-1,4-naphtoquinone 5, in high yield and purity. In the present study, emphasis was given for selecting the reagents and solvents, optimizing the reaction conditions, recovery and reuse of solvents and silver salt. This optimized novel process is cost-effective and would generate less effluent. [ABSTRACT FROM AUTHOR]

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. Our efforts towards optimization of hydrolysis reaction and recrystallization of 5 with the use of the small volume of solvent combination had made the process to be more costeffective and commercially viable for large-scale manufacturing. [ABSTRACT FROM AUTHOR]