1,2-Bis(dimethoxyphosphoryl)benzene
[CAS# 15104-46-8]

Identification

• Classification: Chemical reagent >> Organic reagent >> Phosphorous compound
• Name: 1,2-Bis(dimethoxyphosphoryl)benzene
• Molecular Formula: C₁₀H₁₆O₆P₂
• Molecular Weight: 294.18
• CAS Registry Number: 15104-46-8
• EC Number: 677-884-5
• SMILES: COP(=O)(C1=CC=CC=C1P(=O)(OC)OC)OC

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 82 - 83 ºC (Expl.)
• Boiling point: 373.6±25.0 ºC 760 mmHg (Calc.)^*
• Flash point: 193.3±43.5 ºC (Calc.)^*
• Index of refraction: 1.478 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS06 Danger
• Hazard Statements: H301-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501
• Transport Information: UN 3464

Discovory and Applicatios

The chemical substance 1,2-bis(dimethoxyphosphoryl)benzene, also known as 1,2-bis(dimethyl phosphonate)benzene, is an aromatic compound featuring two phosphonate ester groups at the 1,2-positions of a benzene ring. It is recognized in organic chemistry as a versatile synthetic intermediate, particularly in the synthesis of organophosphorus compounds, pharmaceuticals, and materials. Its discovery and applications are well-documented in the literature, rooted in the development of phosphonate chemistry and aromatic functionalization.

The origins of this compound are tied to the study of organophosphorus compounds, which gained prominence in the early 20th century for their applications in agrochemicals, flame retardants, and ligands. Phosphonate esters, valued for their stability and reactivity in reactions like the Horner-Wadsworth-Emmons (HWE) olefination, became key synthetic tools in the 1950s following the work of Leopold Horner and William Wadsworth. The specific placement of two dimethoxyphosphoryl groups at the 1,2-positions of benzene emerged in the late 20th century, driven by the need for bis-phosphonates as precursors for complex molecules in medicinal and materials chemistry. Advances in aromatic substitution and phosphonate synthesis during the 1960s and 1970s enabled the efficient production of such compounds.

Synthetically, 1,2-bis(dimethoxyphosphoryl)benzene is typically prepared through a straightforward process. A common route starts with 1,2-dichlorobenzene or 1,2-dibromobenzene, which undergoes a Michaelis-Arbuzov reaction with trimethyl phosphite in the presence of a nickel or palladium catalyst. This reaction replaces the halogens with dimethoxyphosphoryl groups, forming the bis-phosphonate. Alternatively, the synthesis can involve lithiation of 1,2-dihalobenzene, followed by quenching with dimethyl chlorophosphate to install the phosphonate groups. These steps rely on well-established protocols in organophosphorus chemistry and aromatic substitution, ensuring high yields and purity.

The primary application of 1,2-bis(dimethoxyphosphoryl)benzene is as a synthetic intermediate in organic chemistry. The two phosphonate groups are highly reactive in HWE olefination reactions, enabling the formation of bis-alkenes or conjugated systems when reacted with aldehydes or ketones under basic conditions. This makes the compound valuable for constructing complex molecular architectures, such as those found in pharmaceutical intermediates or organic semiconductors. In medicinal chemistry, bis-phosphonates are explored for their potential in drug design, particularly for bone-related disorders, due to their ability to chelate calcium and bind to biological targets. The ortho-disubstituted benzene ring provides a rigid scaffold, enhancing the compound’s utility in designing molecules with specific spatial arrangements.

In materials chemistry, the compound is used to synthesize flame-retardant polymers, ligands for metal coordination, and precursors for organic electronics, where the phosphonate groups contribute to thermal stability and electronic properties. In academic research, it serves as a model for studying bis-phosphonate reactivity, HWE reaction mechanisms, and aromatic phosphonylation. Its synthesis has contributed to the optimization of catalytic phosphonate formation and regioselective functionalization techniques.

The significance of 1,2-bis(dimethoxyphosphoryl)benzene lies in its role as a multifunctional intermediate that combines the synthetic versatility of bis-phosphonate groups with the structural rigidity of a benzene ring. Its development reflects progress in organophosphorus chemistry and aromatic substitution. By enabling the efficient synthesis of complex molecules with applications in pharmaceuticals, materials, and beyond, it has become a critical tool in advancing chemical research.

References

2006. Conformational analysis of mono-and bis(dimethoxyphosphoryl)benzenes. Russian Journal of General Chemistry, 76(3).
DOI: 10.1134/s1070363206030169

2006. A methodology for synthesis of primary o-phenylenebisphosphines and o-chlorophenylphosphines. Russian Journal of General Chemistry, 76(6).
DOI: 10.1134/s1070363206060089

2007. Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Proceedings of the National Academy of Sciences of the United States of America, 104(30).
DOI: 10.1073/pnas.0702760104