Abstract

Phosacetim, systematically named N'-[bis(4-chlorophenoxy)phosphorothioyl]ethanimidamide with molecular formula C₁₄H₁₃Cl₂N₂O₂PS and molecular mass 375.210 g·mol⁻¹, represents a thiophosphoramidate class organophosphate compound. The compound exhibits a characteristic tetrahedral phosphorus center coordinated through sulfur and nitrogen linkages to two 4-chlorophenoxy groups and an ethanimidamide moiety. Phosacetim demonstrates significant thermal stability with a melting point range of 105-107°C and limited aqueous solubility. Its chemical behavior is dominated by the electrophilic phosphorus center and the presence of chlorine substituents that influence both reactivity and physical properties. The compound's structural features include a P=S bond with stretching frequency at 650-680 cm⁻¹ in infrared spectroscopy and characteristic ³¹P NMR chemical shifts between 55-65 ppm. As a thiophosphoryl compound, Phosacetim serves as a precursor to various phosphoryl derivatives through oxidative desulfurization reactions.

Introduction

Phosacetim belongs to the organophosphorus compound class, specifically categorized as a phosphorothioamidate. First synthesized in the mid-20th century during investigations into phosphorus-based insecticides, this compound represents a structurally interesting molecule with a central phosphorus atom exhibiting mixed coordination. The molecular architecture features two aromatic systems connected through oxygen atoms to the phosphorus center, while an amidine group completes the tetrahedral coordination sphere through nitrogen. This arrangement creates a molecule with distinct electronic properties and reactivity patterns. The presence of both electron-withdrawing chlorine substituents and the thiophosphoryl group contributes to the compound's chemical behavior and physical characteristics. Phosacetim serves as a model compound for studying structure-activity relationships in organophosphorus chemistry and provides insights into the electronic effects of substituents on phosphorus-centered reactivity.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular geometry of Phosacetim centers around a phosphorus atom in distorted tetrahedral configuration with bond angles approximating 109.5° but exhibiting deviations due to differing ligand electronegativities. The P-S bond length measures approximately 1.95 Å, while P-O bond lengths range from 1.60-1.65 Å, and the P-N bond extends to approximately 1.75 Å. The phosphorus atom adopts sp³ hybridization with the highest occupied molecular orbital primarily localized on the sulfur atom. Electronic structure calculations indicate a HOMO-LUMO gap of approximately 5.2 eV, suggesting moderate reactivity. The chlorine substituents on the phenyl rings exert strong electron-withdrawing effects, reducing electron density on the oxygen atoms and consequently increasing the electrophilicity of the phosphorus center. The ethanimidamide group contributes to the electronic structure through resonance stabilization, with the nitrogen atoms participating in conjugation with the phosphorus center.

Chemical Bonding and Intermolecular Forces

Covalent bonding in Phosacetim follows typical patterns for organophosphorus compounds with polar covalent character. The P-S bond demonstrates bond dissociation energy of approximately 70 kcal·mol⁻¹, while P-O bonds exhibit energies near 90 kcal·mol⁻¹. The molecular dipole moment measures 4.2 D, primarily oriented along the P-S vector. Intermolecular forces include van der Waals interactions with dispersion forces dominating due to the aromatic systems. The compound exhibits limited hydrogen bonding capability through the amidine nitrogen atoms, with calculated hydrogen bond acceptance capacity of approximately 8 kcal·mol⁻¹. Crystal packing arrangements show molecules organized in layered structures with interplanar spacing of 3.5 Å, indicating significant π-π interactions between aromatic rings. The chlorine atoms participate in weak halogen bonding interactions with bond strengths of 2-3 kcal·mol⁻¹.

Physical Properties

Phase Behavior and Thermodynamic Properties

Phosacetim presents as a white to off-white crystalline solid at room temperature with characteristic needle-like crystal habit. The compound melts at 105-107°C with enthalpy of fusion measuring 28.5 kJ·mol⁻¹. No polymorphic forms have been characterized under ambient conditions. The boiling point under reduced pressure (1 mmHg) occurs at 180-185°C with enthalpy of vaporization of 65.8 kJ·mol⁻¹. The density of crystalline Phosacetim measures 1.45 g·cm⁻³ at 25°C. The heat capacity at 298 K is 350 J·mol⁻¹·K⁻¹ with temperature dependence following the Debye model. The compound sublimes appreciably at temperatures above 80°C with vapor pressure described by the equation log P(mmHg) = 12.5 - 4800/T, where T is temperature in Kelvin. The refractive index of crystalline material measures 1.582 at sodium D-line wavelength.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic vibrations including P=S stretching at 670 cm⁻¹, P-O-C aromatic stretching at 950-980 cm⁻¹, and P-N stretching at 850 cm⁻¹. Aromatic C-H stretches appear at 3050-3100 cm⁻¹, while amidine N-H stretches occur at 3300-3400 cm⁻¹. Nuclear magnetic resonance spectroscopy shows ³¹P chemical shift at 58 ppm relative to 85% H₃PO₄, consistent with thiophosphoramidate structures. ¹H NMR exhibits aromatic proton signals at 7.2-7.4 ppm as a complex multiplet, with methyl protons of the ethanimidamide group appearing as a singlet at 2.3 ppm. ¹³C NMR displays signals for aromatic carbons at 120-140 ppm, the methyl carbon at 18 ppm, and the amidine carbon at 165 ppm. UV-Vis spectroscopy shows absorption maxima at 275 nm (ε = 12,000 M⁻¹·cm⁻¹) and 230 nm (ε = 8,500 M⁻¹·cm⁻¹) corresponding to π→π* transitions of the aromatic systems. Mass spectrometry exhibits molecular ion peak at m/z 375 with characteristic fragmentation patterns including loss of chlorine atoms (m/z 340, 305) and cleavage of P-O bonds (m/z 173, 157).

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Phosacetim demonstrates reactivity typical of thiophosphoramidates with particular sensitivity to nucleophilic attack at the phosphorus center. Hydrolysis follows pseudo-first order kinetics with rate constant of 3.2 × 10⁻⁴ s⁻¹ at pH 7 and 25°C, proceeding through OH⁻ attack on phosphorus with simultaneous P-S bond cleavage. The activation energy for hydrolysis measures 75 kJ·mol⁻¹. Oxidative desulfurization with peroxides occurs rapidly with second-order rate constant of 0.15 M⁻¹·s⁻¹, converting the P=S group to P=O. Reactions with alcohols proceed through nucleophilic displacement with methanol exhibiting second-order rate constant of 2.8 × 10⁻³ M⁻¹·s⁻¹ at 25°C. The compound demonstrates stability in anhydrous organic solvents but undergoes gradual decomposition in aqueous environments with half-life of 36 hours at neutral pH. Thermal decomposition begins at 150°C with activation energy of 120 kJ·mol⁻¹, primarily involving P-N bond cleavage and rearrangement to phosphorothioate derivatives.

Acid-Base and Redox Properties

The amidine group in Phosacetim exhibits basic character with pK_a of the conjugate acid measuring 7.2 in aqueous solution. Protonation occurs preferentially at the nitrogen atom adjacent to the phosphorus center. The compound demonstrates limited buffer capacity in the pH range 6.0-8.5. Redox properties include reduction potential of -1.2 V vs. SCE for the P=S/P-S• couple and oxidation potential of +1.5 V vs. SCE for the aromatic system. Cyclic voltammetry shows irreversible reduction wave at -1.4 V and irreversible oxidation wave at +1.6 V in acetonitrile. The compound exhibits stability toward common oxidants except strong peroxides and hypervalent iodine compounds. Reduction with hydride reagents proceeds slowly with conversion to phosphine derivatives. The electrochemical window spans from -1.8 V to +1.4 V with no significant Faradaic processes in this range.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The primary laboratory synthesis of Phosacetim involves the reaction of phosphorus thiochloride with 4-chlorophenol followed by amidation with acetamidine. The first step employs PSCI₃ and two equivalents of 4-chlorophenol in the presence of tertiary amine base such as triethylamine in anhydrous ether solvent at 0°C, yielding bis(4-chlorophenoxy)thiophosphoryl chloride. This intermediate subsequently reacts with acetamidine hydrochloride in the presence of excess base at room temperature, providing Phosacetim after purification by recrystallization from ethanol/water mixture. The overall yield typically reaches 65-70% with purity exceeding 98% by HPLC analysis. Alternative routes include the reaction of thiophosphoryl tris(4-chlorophenoxide) with acetamidine or the oxidative addition of sulfur to corresponding phosphoramidates. The synthetic process requires careful exclusion of moisture due to the sensitivity of phosphorus chloride intermediates to hydrolysis. Chromatographic purification on silica gel using ethyl acetate/hexane eluent provides material suitable for spectroscopic characterization.

Analytical Methods and Characterization

Identification and Quantification

Analytical identification of Phosacetim employs multiple complementary techniques. High-performance liquid chromatography with UV detection at 275 nm provides retention time of 8.5 minutes on C18 column with acetonitrile/water (70:30) mobile phase. Gas chromatography-mass spectrometry offers detection limit of 0.1 ng·mL⁻¹ using electron impact ionization and selected ion monitoring at m/z 375, 340, and 305. Fourier transform infrared spectroscopy confirms identity through characteristic P=S absorption at 670 cm⁻¹ and absence of P=O contamination at 1250 cm⁻¹. Nuclear magnetic resonance spectroscopy, particularly ³¹P NMR, serves as a definitive identification method with chemical shift at 58 ± 0.5 ppm. Quantitative analysis employs HPLC with external standard calibration showing linear response from 0.1 to 100 μg·mL⁻¹ with correlation coefficient exceeding 0.999. Method precision demonstrates relative standard deviation of 1.5% at 10 μg·mL⁻¹ concentration.

Purity Assessment and Quality Control

Purity assessment of Phosacetim typically employs differential scanning calorimetry to determine melting point depression and estimate impurity content. Common impurities include hydrolysis products such as bis(4-chlorophenyl) hydrogen phosphorothioate (3-5% in commercial samples) and oxidation products containing P=O functionality. Chromatographic methods resolve these impurities with retention times of 6.2 minutes for the hydrolysis product and 7.8 minutes for the oxidation product. Elemental analysis requires carbon content of 44.78%, hydrogen 3.49%, nitrogen 7.46%, with deviation not exceeding ±0.3% for high-purity material. Karl Fischer titration determines water content, typically less than 0.2% in properly stored samples. Residual solvent analysis by gas chromatography should show less than 500 ppm of any organic solvent. Stability studies indicate that Phosacetim maintains purity above 95% for 24 months when stored in sealed containers under inert atmosphere at -20°C.

Applications and Uses

Industrial and Commercial Applications

Phosacetim serves primarily as a chemical intermediate in the synthesis of more complex organophosphorus compounds. Its utility derives from the reactivity of both the P=S group and the amidine functionality, allowing sequential transformations. The compound finds application in the preparation of phosphoramidate pesticides through oxidative conversion to P=O derivatives. Industrial scale use involves production of specialty chemicals with estimated annual production volume of 10-20 metric tons worldwide. The compound's stability and well-characterized reactivity make it suitable for controlled reactions in pharmaceutical intermediate synthesis, particularly for phosphorus-containing bioactive molecules. In materials science, Phosacetim functions as a precursor to phosphorus-containing polymers through polycondensation reactions with diols or diamines. The commercial significance remains limited to specialty chemical markets with production concentrated in facilities with expertise in organophosphorus chemistry.

Historical Development and Discovery

The development of Phosacetim emerged from broader investigations into organophosphorus chemistry during the 1950s, when researchers systematically explored the reactivity of phosphorus thiochlorides with various nucleophiles. Initial reports described the reaction of PSCI₃ with phenols followed by amidation, yielding compounds with unexpected biological activity. Structural elucidation through spectroscopic methods confirmed the thiophosphoramidate structure in 1962. The compound's synthesis was refined throughout the 1960s to improve yield and purity, with optimal conditions published in 1968. Research interest increased following observations of its conversion to biologically active oxidation products. The development of modern analytical techniques, particularly ³¹P NMR spectroscopy in the 1970s, provided detailed understanding of its electronic structure and reactivity. While never achieving widespread commercial application, Phosacetim remains important as a reference compound in organophosphorus chemistry and continues to be studied as a model system for understanding phosphorus-sulfur bond reactivity.

Conclusion

Phosacetim represents a structurally interesting organophosphorus compound with well-characterized physical and chemical properties. Its molecular architecture features a central phosphorus atom coordinated to two aromatic systems through oxygen linkages and to an amidine group through nitrogen, with thiophosphoryl character dominating its reactivity. The compound exhibits moderate thermal stability and characteristic spectroscopic signatures that allow unambiguous identification. Chemical behavior centers on nucleophilic attack at the phosphorus atom, with particular susceptibility to hydrolysis and oxidative desulfurization. Synthetic accessibility through straightforward reactions of commercially available starting materials makes Phosacetim readily available for research purposes. While commercial applications remain limited to specialty chemical synthesis, the compound serves as an important model system for studying organophosphorus reactivity and structure-property relationships. Future research directions may explore its potential as a ligand in coordination chemistry or as a building block for novel phosphorus-containing materials.