137732-39-9

Basic information

• Product Name: cis-Atovaquone
• Synonyms: cis-Atovaquone;1,4-Naphthalenedione,2-[cis-4-(4-chlorophenyl)cyclohexyl]-3- hydroxy-;Atovaquone EP Impurity B (Atovaquone Related Compound A);2-((1s,4s)-4-(4-chlorophenyl)cyclohexyl)-3- hydroxynaphthalene-1,4-dione
• CAS NO: 137732-39-9
• Molecular Formula: C₂₂H₁₉ClO₃
• Molecular Weight: 366.83746
• Product Categories: Aromatics, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 137732-39-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 535.0±50.0 °C(Predicted)
• Appearance: /
• Density: 1.349±0.06 g/cm3(Predicted)
• Storage Temp.: Room Temperature, under inert atmosphere
• Solubility: Chloroform (Slightly), Dichloromethane (Slightly, Acetonitrile
• PKA: 5.01±0.10(Predicted)
• CAS DataBase Reference: cis-Atovaquone(CAS DataBase Reference)
• NIST Chemistry Reference: cis-Atovaquone(137732-39-9)
• EPA Substance Registry System: cis-Atovaquone(137732-39-9)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 137732-39-9(Hazardous Substances Data)

Usage

Uses

cis-Atovaquone is the cis-isomer of Atovaquone (A793500), a hydroxynaphthoquinone derivative that inhibits mitochondrial electron transport.

Upstream product

• 83-72-7 2-hydroxynaphtho-1,4-quinone 
• 1010-60-2 2-chloro-1,4-naphthoquinone 
• 1071223-07-8 cis-2-[4-(4-chlorophenyl)cyclohexyl]-3-chloro-1,4-naphthoquinone 
• 1203609-10-2 cis-2-[4-(4-chlorophenyl)cyclohexyl]-1,4-naphthoquinone 
• 1409957-42-1 cis-1a-(4-(4-chlorophenyl)cyclohexyl)naphtho[2,3-b]oxirene-2,7(1aH,7aH)dione 
• 94015-53-9 atovaquone 

Downstream Products

• 95233-18-4 atovaquone 

Relevant articles and documents

Late-Stage C-H Alkylation of Heterocycles and 1,4-Quinones via Oxidative Homolysis of 1,4-Dihydropyridines

Under oxidative conditions, 1,4-dihydropyridines (DHPs) undergo a homolytic cleavage, forming exclusively a Csp3-centered radical that can engage in the C-H alkylation of heterocyclic bases and 1,4-quinones. DHPs are readily prepared from aldehydes, and considering that aldehydes normally require harsh reaction conditions to take part in such transformations, with mixtures of alkylated and acylated products often being obtained, this net decarbonylative alkylation approach becomes particularly useful. The present method takes place under mild reaction conditions and requires only persulfate as a stoichiometric oxidant, making the procedure suitable for the late-stage C-H alkylation of complex molecules. Notably, structurally complex pharmaceutical agents could be functionalized or prepared with this protocol, such as the antimalarial Atovaquone and antitheilerial Parvaquone, thus evidencing its applicability. Mechanistic studies revealed a likely radical chain process via the formation of a dearomatized intermediate, providing a deeper understanding of the factors governing the reactivity of these radical forebears.

NOVEL METHOD FOR PREPARATION OF ATOVAQUONE

Provided is a process of preparation of 2-[trans,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy- 1,4-naphthoquinone, i.e. Atovaquone [I] which is cost effective, green, and eco-friendly process, without separation of any diastereomers or geometric isomers of intermediates obtained during the reactions. Also provided is separation of 'cis' and 'trans ' isomer of intermediates VI, VII and VIII through selective crystallization in an appropriate solvent. A method for converting 2-[cis,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone to 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone in presence of Lewis/ Bronsted acid is also provided. A process for preparation of compound 2-(4-(4- chlorophenyl)- 1 -hydroxy cyclohexyl)-3,4-dihydronaphthalen- 1 (2H)-one [IV] comprising condensation of (1,2-dihydronaphthalen-4-yloxy)trimethylsilane [II] with 4-(4- chlorophenyl)cyclohexanone [III] in presence of Lewis acid in organic solvent. The invention also encompasses a highly efficient and atomeconomic process for synthesis of compound [III] i.e. 4-(4-chlorophenyl)cyclohexanone as well as a process for synthesis of 2-[cis-4-(4'- chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone. Further provided is a process for isomerization of cis- Atovaquone i.e. 2-[cis-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4- naphthoquinone to tnms-Atovaquone i.e. 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3- hydroxy- 1,4-naphthoquinone in presence of Lewis acid.