For chemists and researchers involved in pharmaceutical synthesis, a deep understanding of the chemical intermediates used is crucial. (R)-Propylene Carbonate, identified by CAS number 16606-55-6, is a molecule of significant interest due to its role as a chiral building block in the production of important APIs, most notably Tenofovir. This article explores its chemical structure, key properties, and common synthesis routes, providing valuable insights for R&D scientists and procurement specialists.

Chemical Structure and Nomenclature

(R)-Propylene Carbonate is a cyclic carbonate ester. Its chemical structure features a five-membered ring, specifically a 1,3-dioxolan-2-one ring, with a methyl group attached at the chiral center (carbon atom at position 4). The designation '(R)' refers to the specific stereochemical configuration at this chiral center, which is critical for its use in asymmetric synthesis. Its molecular formula is C₄H₆O₃, and its molecular weight is approximately 102.09 g/mol. Common synonyms include (R)-(+)-1,2-Propylene Carbonate and (4R)-4-methyl-1,3-dioxolan-2-one.

Key Physicochemical Properties

(R)-Propylene Carbonate is typically characterized by the following properties:

  • Appearance: Colorless to light yellow liquid.
  • Density: Around 1.189 g/mL at 20-25°C.
  • Boiling Point: Approximately 240°C at standard pressure.
  • Flash Point: Typically above 230°F (>110°C), indicating relatively low flammability.
  • Solubility: Soluble in various organic solvents and has some miscibility with water.
  • Polarity: It is a polar aprotic solvent, making it effective for dissolving ionic compounds and facilitating certain reaction mechanisms.
  • Enantiomeric Purity: High enantiomeric excess (e.e. ≥99.0%) is a key specification for its use in chiral synthesis.

These properties contribute to its utility as a reaction medium and a reactive intermediate. Its stability, polarity, and chirality are all essential for its role in complex organic transformations.

Synthesis Pathways for (R)-Propylene Carbonate

The synthesis of enantiomerically pure (R)-Propylene Carbonate is typically achieved through several methods:

  • From (R)-Propylene Oxide: A common route involves the cycloaddition of carbon dioxide to (R)-propylene oxide. This reaction is often catalyzed, for example, by specific metal complexes, to yield the desired cyclic carbonate. This method is considered atom-economical.
  • Resolution of Racemic Propylene Carbonate: Racemic propylene carbonate can be synthesized and then resolved into its enantiomers using chiral separation techniques, such as chiral chromatography. While effective, this method can be more costly and less efficient for large-scale production compared to direct asymmetric synthesis.
  • From Chiral Pool Materials: Alternative routes might involve starting from other readily available chiral compounds through multi-step synthesis.

Manufacturers specializing in fine chemicals and pharmaceutical intermediates will have optimized these processes to ensure high yields and consistent quality, particularly the enantiomeric purity required for pharmaceutical applications.

Applications in Pharmaceutical Synthesis

The primary driver for the demand of high-purity (R)-Propylene Carbonate is its use as a key chiral intermediate in the synthesis of Tenofovir (CAS: 147127-20-6) and its prodrugs, such as Tenofovir Disoproxil Fumarate (CAS: 202138-50-9). Its chiral nature allows for the precise introduction of stereochemistry required for the biological activity of these antiviral drugs. For companies looking to buy this compound, partnering with manufacturers that provide detailed technical specifications and ensure batch-to-batch consistency is paramount for successful API production.

Understanding the chemical properties and synthesis of (R)-Propylene Carbonate empowers R&D teams to optimize their synthetic routes and procurement specialists to make informed decisions when sourcing this critical intermediate. Its continued importance in pharmaceutical manufacturing highlights the value of specialized chiral chemicals.