6-Ethynyl-4,4-dimethylthiochroman
[CAS# 118292-06-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate
• Name: 6-Ethynyl-4,4-dimethylthiochroman
• Synonyms: 4,4-Dimethyl-6-ethynylthiochroman; 6-Ethynyl-3,4-dihydro-4,4-dimethyl-2H-1-benzothiopyran
• Molecular Formula: C₁₃H₁₄S
• Molecular Weight: 202.32
• CAS Registry Number: 118292-06-1
• EC Number: 601-515-9
• SMILES: CC1(CCSC2=C1C=C(C=C2)C#C)C

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 69-72 °C (Expl.), 69-72 °C (Expl.)
• Boiling point: 299.2±39.0 °C 760 mmHg (Calc.)^*
• Flash point: 127.8±23.7 °C (Calc.)^*
• Index of refraction: 1.597 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

6-Ethynyl-4,4-dimethylthiochroman is a synthetic organic compound belonging to the thiochroman family, a group of heterocyclic molecules containing a sulfur atom fused within a chroman-like bicyclic framework. The introduction of an ethynyl group at the 6-position and the dimethyl substitution at the 4-position confer distinct structural and electronic properties that influence its reactivity and potential applications in chemical and medicinal research.

The discovery and initial synthesis of 6-ethynyl-4,4-dimethylthiochroman stemmed from systematic efforts in heterocyclic chemistry during the second half of the 20th century. Researchers were interested in modifying chroman and thiochroman scaffolds to explore novel molecular frameworks with potential pharmaceutical relevance. The compound is generally prepared through multi-step synthetic pathways, beginning with appropriately substituted thiochroman precursors. Methods often involve Friedel–Crafts alkylation or cyclization strategies to construct the thiochroman ring, followed by selective introduction of the ethynyl substituent through palladium-catalyzed cross-coupling reactions such as the Sonogashira coupling. These synthetic approaches allow for fine control over substitution patterns, facilitating the exploration of chemical diversity.

From an application perspective, 6-ethynyl-4,4-dimethylthiochroman has primarily been studied as an intermediate in organic synthesis rather than as a final pharmacological agent. The ethynyl functional group serves as a versatile handle for further chemical modification, enabling the introduction of additional substituents via coupling or addition reactions. This reactivity makes the compound useful in the design and preparation of more complex molecules with potential biological activity.

In medicinal chemistry, thiochroman derivatives have attracted attention because of their structural similarity to flavonoids and chromans, natural products often associated with antioxidant, anti-inflammatory, and antimicrobial activities. Although 6-ethynyl-4,4-dimethylthiochroman itself has not been extensively developed into a therapeutic agent, its scaffold provides a useful basis for structure–activity relationship studies. Incorporation of the ethynyl group enhances molecular rigidity and can modulate interactions with biological targets, which may be relevant in drug design efforts focused on kinase inhibition or receptor modulation.

In materials science, the compound’s ethynyl group also lends itself to polymerization and functionalization, offering potential in the development of advanced materials, though this application remains at a conceptual and experimental stage. Its sulfur-containing heterocycle further broadens the scope of chemical reactivity, opening avenues for the design of sulfur-rich molecular frameworks with desirable physicochemical properties.

Overall, 6-ethynyl-4,4-dimethylthiochroman is a synthetically derived heterocyclic compound characterized by a thiochroman core modified with an ethynyl group and dimethyl substitution. While it is not a widely used standalone bioactive molecule, it serves as an important intermediate in synthetic organic chemistry and contributes to the broader exploration of sulfur-containing heterocycles in pharmaceutical and materials research. Its development illustrates the role of synthetic analogues in expanding the chemical space available for future applications.

References

2008. Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(4-phenylethynyl-phenyl)-1H-benzimidazoles and N-substituted 2[4-(4,4-dimethyl-thiochroman-6-yl-ethynyl)-phenyl)-1H-benzimidazoles. European Journal of Medicinal Chemistry.
DOI: 10.1016/j.ejmech.2007.07.007

2006. Process for the preparation of Tazarotene. European Patent.
Patent: EP1700855A1

2003. Tazarotene. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-20-0013