7-Fluoro-8-[(triisopropylsilyl)ethynyl]naphthalene-1,3-diol
[CAS# 2621932-34-9]

Identification

• Classification: Organic raw materials >> Aryl compounds >> Naphthalenes
• Name: 7-Fluoro-8-[(triisopropylsilyl)ethynyl]naphthalene-1,3-diol
• Molecular Formula: C₂₁H₂₇FO₂Si
• Molecular Weight: 358.52
• CAS Registry Number: 2621932-34-9
• SMILES: CC(C)[Si](C#CC1=C(C=CC2=CC(=CC(=C21)O)O)F)(C(C)C)C(C)C

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 458.2±37.0 ºC 760 mmHg (Calc.)^*
• Flash point: 230.9±26.5 ºC (Calc.)^*
• Index of refraction: 1.565 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Discovory and Applicatios

7-Fluoro-8-[(triisopropylsilyl)ethynyl]naphthalene-1,3-diol is a fluorinated naphthalenediol bearing a TIPS-protected ethynyl substituent. Its molecular formula is C₂₁H₂₇FO₂Si and it is catalogued under CAS number 2621932-34-9. The compound is a bench-stable, protected alkynylated naphthalenediol used principally as a synthetic building block in organic and medicinal chemistry. The 1,3-dihydroxy pattern on the naphthalene core provides two orthogonal handles for selective functionalisation, while the 7-fluoro substituent modulates the electronic properties of the aromatic system; the triisopropylsilyl (TIPS) group protects the ethynyl unit during multistep sequences and can be removed under standard desilylation conditions to reveal the terminal alkyne for further coupling or cyclisation.

The immediate chemical provenance of this material in disclosed preparative sequences is the selective alkynylation of 7-fluoronaphthalene-1,3-diol derivatives. Documented synthetic routes use an alkynyl-halide source such as 2-bromoethynyl(triisopropyl)silane and a metal-mediated coupling or direct alkynylation protocol to install the TIPS-protected ethynyl group at C-8 of the naphthalene ring, with potassium acetate or other bases and transition-metal catalysts reported for the transformation. Typical work-up and purification provide the protected diol as a crystalline or oil-like material that is handled and stored under inert atmosphere at low temperature to prevent oxidative or hydrolytic degradation of the polyfunctional aromatic core.

Applications for 7-fluoro-8-[(triisopropylsilyl)ethynyl]naphthalene-1,3-diol arise from two principal utilities: (1) as a masked ethynyl synthon for cross-coupling, cycloaddition and C(sp)–C(sp2) bond-forming reactions after desilylation; and (2) as a fluorinated aromatic building block where the 1,3-dihydroxy motif and the 7-fluoro substituent influence regioselectivity and electronic properties in downstream transformations. After TIPS removal, the exposed terminal alkyne can participate in Sonogashira-type couplings, copper-catalysed azide–alkyne cycloadditions (CuAAC, “click” chemistry), oxidative homocouplings to form diynes, or intramolecular cyclisations to give fused polycyclic structures. The two hydroxyl groups enable selective protection, esterification, etherification or oxidative manipulation to access naphthoquinone-like motifs or fused heterocycles. Fluorination at C-7 is often retained into final products to tune lipophilicity, metabolic stability and binding interactions in small-molecule discovery.

The presence of a TIPS-protected ethynyl in a fluorinated naphthalenediol scaffold has made the compound suitable for use in discovery chemistry workflows and in patent-disclosed synthetic sequences. One documented preparative sequence uses the coupling of 7-fluoronaphthalene-1,3-diol with 2-bromoethynyl(triisopropyl)silane in the presence of base and a transition-metal promoter to generate the 8-alkynylated product; this intermediate is advanced in multistep schemes to elaborated targets. In practice, chemists store the protected derivative at low temperature under inert gas and perform desilylation (for example with TBAF or buffered fluoride sources) immediately prior to transformations that require the free alkyne. Care is taken to preserve the diol motif during cross-coupling conditions by appropriate protection or choice of chemoselective conditions.

From a synthetic-methodology perspective, installation of alkynyl groups onto electron-rich or electron-deficient aromatic systems can be achieved either by traditional Sonogashira coupling of an aryl halide with a terminal alkyne or via “inverse” alkynylation strategies employing alkynyl halides and C–H or O-directed routes; the choice depends on substrate functionality and desired regiocontrol. Fluorinated naphthalene scaffolds present regioselectivity challenges that are typically managed by using pre-functionalised ring precursors and directed coupling strategies. The TIPS group is preferred for protecting alkynes in multistep synthesis because it is robust under many reaction conditions yet removable under mild fluoride-mediated conditions.

In summary, 7-fluoro-8-[(triisopropylsilyl)ethynyl]naphthalene-1,3-diol is a verified, commercially available protected alkynyl naphthalenediol used as a modular building block for constructing more complex fluorinated polycycles and for late-stage introduction of alkyne functionality in synthetic and medicinal chemistry projects.

References

Dudnik AS & Gevorgyan V (2010) Formal inverse Sonogashira reaction: direct alkynylation of arenes and heterocycles with alkynyl halides. Angewandte Chemie International Edition 49 12 2096–2098.
DOI: 10.1002/anie.200906755

Kanwal I, Mujahid A, Rasool N, Rizwan K, Malik A, Ahmad G, Shah SAA, Rashid U & Nasir NM (2020) Palladium and copper catalysed Sonogashira cross coupling: an excellent methodology for C–C bond formation over 17 years — a review. Catalysts 10 443.
DOI: 10.3390/catal10040443

Almirall LLC / AstraZeneca (2024) WO2024178313A1: KRAS modulators (example preparation includes 7-fluoro-8-((triisopropylsilyl)ethynyl)naphthalene-1,3-diol). World Intellectual Property Organization patent application WO2024/178313 A1. WO2024178313A1