2,5,2',5'-Tetramethyl-[2.2]paracyclophane
[CAS# 35233-71-7]

Identification

• Classification: Chemical reagent >> Organic reagent >> Aromatic hydrocarbon reagent
• Name: 2,5,2',5'-Tetramethyl-[2.2]paracyclophane
• Synonyms: 5,12,13,16-tetramethyltricyclo[8.2.2.24,7]hexadeca-1(13),4,6,10(14),11,15-hexaene
• Molecular Formula: C₂₀H₂₄
• Molecular Weight: 264.40
• CAS Registry Number: 35233-71-7
• SMILES: CC1=CC2=CC(=C1CCC3=C(C=C(CC2)C=C3C)C)C

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 387.0±37.0 ºC 760 mmHg (Calc.)^*
• Flash point: 205.4±17.2 ºC (Calc.)^*
• Index of refraction: 1.566 (Calc.)^*

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

Discovory and Applicatios

2,5,2′,5′-Tetramethyl-[2.2]paracyclophane is a highly substituted derivative of the [2.2]paracyclophane scaffold, bearing four methyl groups at the 2,5 positions on each of the two benzene rings. The general [2.2]paracyclophane framework consists of two para-linked benzene rings connected by two ethylene bridges (–CH₂–CH₂–), resulting in a rigid, cofacial aromatic structure. In the tetramethyl variant, the addition of methyl substituents increases steric congestion, alters electronic properties and enhances its utility as a building block in advanced molecular and materials chemistry.

The compound’s origin can be traced back to the pioneering work on cyclophanes in the mid-20th century, when chemists explored bridged aromatic systems as probes of aromaticity, strain, and three-dimensional π-interactions. The [2.2]paracyclophane core was first synthesized by Brown and Farthing in 1949 via pyrolysis of para-xylene under low-pressure conditions. Over subsequent decades, chemists developed functionalized derivatives, including methyl-substituted versions like 2,5,2′,5′-tetramethyl-[2.2]paracyclophane, to modulate the electronic and steric attributes of the cyclophane scaffold for specific applications.

In terms of synthesis, the tetramethyl derivative is typically accessed by multi-step routes starting from a suitably substituted xylylene precursor. One pathway involves selective bromomethylation or alkylation of methyl-substituted benzene rings followed by intramolecular bridge formation to generate the cyclophane structure. The synthetic route must accommodate the steric hindrance introduced by the methyl groups and maintain the correct connectivity of the two aromatic rings and their bridging chains. Purification and characterization often rely on crystallization and spectroscopic methods (such as NMR and X-ray diffraction) to confirm the unique conformational and planar-chiral features of these derivatives.

The applications of 2,5,2′,5′-tetramethyl-[2.2]paracyclophane arise from its rigid, chiral, and π-stacked architecture. One prominent use is as a monomer or building block in the design of advanced materials, such as chiral ligands, π-functional polymers, and host-guest systems. Its rigid scaffold helps maintain distance- and orientation-specific interactions, making it valuable in supramolecular chemistry and molecular electronics where controlled spatial arrangement of aromatic units is essential. For example, substituted [2.2]paracyclophanes are used to build donor-acceptor systems, chiral stationary phases for chromatography, and cyclophane-based polymers exhibiting unique optical or electronic properties.

In addition, the tetramethyl substitution enhances solubility in organic media and tunes the HOMO–LUMO gap by slightly increasing electron density in the aromatic rings. This makes the compound of interest in materials research focusing on organic light-emitting diodes (OLEDs), molecular wires, and sensors. Because the ring-to-ring distance in [2.2]paracyclophanes is fixed by the ethylene bridges, functionalization with methyl groups offers a way to fine-tune packing, crystal structure, and electronic coupling between the aromatic faces, which are critical parameters in device-scale applications.

Mechanistically, the compound is used as a structural probe in physical organic chemistry to understand how substituents influence the strain energy, aromatic delocalization, and through-space π-interactions in cyclophanes. The incorporation of the methyl substituents intensifies the strain and distorts the aromatic rings compared to the unsubstituted parent, providing valuable insights into structure–property relationships in highly constrained aromatic systems.

From a practical standpoint, handling the compound requires standard precautions for aromatic hydrocarbons with bridging chains: it is typically a crystalline solid or dense liquid depending on substitution, stable under ambient conditions but sensitive to strong oxidizing agents. Because of its rigid structure and limited solubility in polar media, specialized solvents and inert atmosphere techniques are sometimes employed during synthesis and purification.

Overall, 2,5,2′,5′-tetramethyl-[2.2]paracyclophane exemplifies the versatility of cyclophane chemistry: a rigid, chiral, and electronically tunable scaffold that serves as both a synthetic challenge and a foundational unit in materials and supramolecular design. Its substituted architecture enhances functionality beyond the parent cyclophane, making it a valuable reagent in research that bridges organic synthesis, materials science, and molecular electronics.

References

Brown CJ, Farthing AC (1949) Preparation and structure of di-p-xylylene. Nature 164 915–916 DOI: 10.1038/164915b0

Hassan Z, Spuling E, Knoll DM, Bräse S (2020) Regioselective functionalization of [2.2]paracyclophanes: recent synthetic progress and perspectives. Angewandte Chemie International Edition 59 6 2156–2170 DOI: 10.1002/anie.201904863

Dodziuk H, Szymański S, Jaźwiński J, et al. (2011) Structure and NMR spectra of some [2.2]paracyclophanes. The dilemma of [2.2]paracyclophane symmetry. Journal of Physical Chemistry A 115 38 10711–10718 DOI: 10.1021/jp205693a