Abstract

Aminocyclopyrachlor, systematically named 6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid (C₈H₈ClN₃O₂), represents a synthetic organic compound belonging to the pyrimidine carboxylic acid chemical family. This compound exhibits a molecular mass of 213.62 g·mol^-1 and manifests as a brown liquid with a density of 1.134 g·mL^-1 at standard temperature and pressure. The molecular architecture incorporates a pyrimidine ring system substituted with carboxylic acid, amino, chloro, and cyclopropyl functional groups, creating a planar conjugated system with distinctive electronic properties. Aminocyclopyrachlor demonstrates significant stability in environmental matrices with soil dissipation half-lives ranging from 3 to over 112 days depending on soil composition. The compound's chemical behavior is characterized by its auxin-mimicking properties and selective activity against broadleaf plants through disruption of gene expression pathways.

Introduction

Aminocyclopyrachlor stands as a significant synthetic organic compound within the pyrimidine carboxylic acid class, first developed and conditionally registered by DuPont in 2010 under the trade name Imprelis. This compound represents an advanced structural analog within the auxin-mimicking herbicide family, specifically engineered for enhanced environmental persistence and selective phytotoxicity. The molecular design incorporates a pyrimidine core functionalized with multiple substituents that confer both chemical stability and biological activity. Structural characterization reveals a conjugated system with delocalized π-electrons across the heterocyclic ring, contributing to its distinctive electronic properties and reactivity patterns. The compound's discovery emerged from systematic structure-activity relationship studies targeting improved herbicidal efficacy with reduced mammalian toxicity profiles compared to earlier auxin-mimicking agents.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The molecular geometry of aminocyclopyrachlor features a nearly planar pyrimidine ring system (C₄N₂) with bond angles approximating 120° at each ring atom, consistent with sp² hybridization. The cyclopropyl substituent at the 2-position adopts a puckered conformation with carbon-carbon bond angles of approximately 60°, creating significant ring strain. X-ray crystallographic analysis reveals the carboxylic acid group at the 4-position lies coplanar with the pyrimidine ring, facilitating conjugation through the π-system. The chloro substituent at the 5-position and amino group at the 6-position occupy positions orthogonal to the ring plane, influencing both electronic distribution and intermolecular interactions.

Electronic structure calculations employing density functional theory at the B3LYP/6-311+G(d,p) level indicate highest occupied molecular orbital (HOMO) electron density primarily localized on the amino group and pyrimidine ring, while the lowest unoccupied molecular orbital (LUMO) shows predominant character on the carboxylic acid functionality and chloro substituent. The HOMO-LUMO gap measures approximately 4.2 eV, consistent with the compound's observed UV-Vis absorption characteristics. Natural bond orbital analysis reveals significant n→π* conjugation between the amino group lone pair and the pyrimidine ring system, with an estimated stabilization energy of 25.3 kJ·mol^-1.

Chemical Bonding and Intermolecular Forces

Covalent bonding in aminocyclopyrachlor exhibits characteristic patterns with carbon-nitrogen bond lengths in the pyrimidine ring measuring 1.337 Å for C2-N3 and 1.347 Å for C6-N1, intermediate between single and double bond character. The carbon-chlorine bond at the 5-position measures 1.742 Å, typical for aryl chlorides. The cyclopropyl ring demonstrates carbon-carbon bond lengths of 1.510 Å with significant bending momentum due to ring strain.

Intermolecular forces dominate the compound's solid-state behavior and solution properties. The carboxylic acid functionality facilitates strong hydrogen bonding with dimerization energy approximately -25.1 kJ·mol^-1 in the gas phase. The amino group participates as both hydrogen bond donor and acceptor, while the chloro substituent engages in halogen bonding interactions with estimated interaction energies of -12.3 kJ·mol^-1 with carbonyl oxygen atoms. The molecular dipole moment measures 4.32 D in the gas phase, oriented from the carboxylic acid toward the chloro substituent. Calculated polarizability measures 18.7 ų, contributing to significant van der Waals interactions in condensed phases.

Physical Properties

Phase Behavior and Thermodynamic Properties

Aminocyclopyrachlor manifests as a brown liquid at ambient conditions with characteristic viscosity of 12.4 mPa·s at 25°C. The compound demonstrates limited volatility with vapor pressure measuring 2.7 × 10^-7 mmHg at 25°C. Thermal analysis reveals decomposition commencing at 215°C without distinct melting behavior, indicating gradual thermal degradation rather than phase transition. The density measures 1.134 g·mL^-1 at 20°C, with temperature dependence following the relationship ρ = 1.156 - 0.00087T (where T in °C) over the range 0-50°C.

Solution thermodynamics indicate enthalpy of solution in water measuring -18.3 kJ·mol^-1 with entropy change of -45.2 J·mol^-1·K^-1 at 25°C. The heat capacity of the liquid phase measures 289 J·mol^-1·K^-1 at 25°C, while the solid phase exhibits Cp = 215 J·mol^-1·K^-1 at -20°C. The refractive index measures 1.542 at 589 nm and 20°C, with temperature coefficient dn/dT = -4.2 × 10^-4 °C^-1.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic vibrations including N-H stretching at 3385 cm^-1 and 3320 cm^-1, C-H stretching of the cyclopropyl group at 3020 cm^-1, and carbonyl stretching of the carboxylic acid dimer at 1685 cm^-1. The pyrimidine ring breathing mode appears at 1585 cm^-1 with C-Cl stretching vibration at 765 cm^-1.

Proton nuclear magnetic resonance spectroscopy in deuterated dimethyl sulfoxide shows the cyclopropyl methine proton as a multiplet at δ 2.15-2.25 ppm, while methylene protons of the cyclopropyl group appear as a complex multiplet at δ 0.95-1.15 ppm. The amino protons exchange rapidly but appear as a broad singlet at δ 6.75 ppm. Carbon-13 NMR reveals the carboxylic carbon at δ 165.8 ppm, pyrimidine C4 at δ 158.2 ppm, C6 at δ 152.4 ppm, and C5 at δ 140.1 ppm. The cyclopropyl carbons appear at δ 15.3 ppm (methine) and δ 8.7 ppm (methylene).

UV-Vis spectroscopy in methanol solution shows absorption maxima at 225 nm (ε = 12,400 M^-1·cm^-1) and 275 nm (ε = 8,200 M^-1·cm^-1), corresponding to π→π* transitions of the conjugated system. Mass spectrometric analysis exhibits molecular ion peak at m/z 213 with characteristic fragmentation patterns including loss of CO₂ (m/z 169), HCl (m/z 177), and cyclopropyl radical (m/z 170).

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Aminocyclopyrachlor demonstrates moderate chemical stability in aqueous systems with hydrolysis rate constants following pseudo-first-order kinetics. The pH-dependent hydrolysis exhibits maximum stability between pH 5-7 with half-life exceeding 90 days at 25°C. Under acidic conditions (pH < 3), hydrolysis proceeds via protonation of the pyrimidine ring nitrogen followed by nucleophilic attack at the 5-position, with rate constant k_acid = 2.3 × 10^-3 M^-1·s^-1 at 25°C. Alkaline hydrolysis (pH > 9) occurs through hydroxide attack at the carbonyl carbon with subsequent decarboxylation, exhibiting rate constant k_base = 4.7 × 10^-2 M^-1·s^-1 at 25°C.

Photochemical degradation follows first-order kinetics with quantum yield Φ = 0.034 in aqueous solution at 290 nm. The primary photodegradation pathway involves homolytic cleavage of the C-Cl bond with formation of chlorine radical and subsequent ring rearrangement. Thermal decomposition commences at 215°C through decarboxylation followed by ring opening, with activation energy E_a = 132 kJ·mol^-1 determined by thermogravimetric analysis.

Acid-Base and Redox Properties

The compound exhibits two ionization centers with pK_a values of 4.72 for the carboxylic acid group and 2.15 for the protonated pyrimidine nitrogen. The isoelectric point occurs at pH 3.44, where the molecule exists predominantly as a zwitterion. The amino group demonstrates negligible basicity with pK_a < 0 for protonation due to electron withdrawal by the pyrimidine ring.

Redox properties indicate reduction potential E_red = -0.87 V vs. standard hydrogen electrode for the one-electron reduction of the pyrimidine ring. Oxidation occurs at E_ox = +1.23 V vs. SHE, primarily involving the amino group. The compound demonstrates stability toward common oxidants including hydrogen peroxide and potassium permanganate but undergoes rapid reduction with sodium borohydride at the carbonyl group.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

Laboratory synthesis of aminocyclopyrachlor proceeds through a convergent multistep route beginning with cyclopropanecarbonitrile and ethyl cyanoacetate. The initial step involves condensation to form 2-cyclopropyl-6-amino-pyrimidin-4(3H)-one under basic conditions with sodium ethoxide in ethanol at 78°C for 6 hours, yielding 78-82%. Subsequent chlorination employs phosphorus oxychloride at reflux temperature (108°C) for 4 hours to introduce the 5-chloro substituent with conversion exceeding 90%.

The final step involves oxidation of the 4-position using potassium permanganate in aqueous acetone at 60°C for 3 hours, achieving carboxylic acid formation with 65-70% yield. Purification employs recrystallization from ethanol-water mixtures to obtain analytical purity exceeding 99.5%. Alternative synthetic pathways include palladium-catalyzed carbonylation of the corresponding bromo derivative using carbon monoxide at 5 atm pressure and 120°C, providing improved yields of 85-88%.

Industrial Production Methods

Industrial production utilizes continuous flow reactor systems with automated process control to ensure consistent quality and yield. The manufacturing process employs the laboratory route scaled to metric ton quantities with modifications for safety and efficiency. Chlorination utilizes thionyl chloride rather than phosphorus oxychloride due to easier handling and reduced waste generation. Oxidation employs catalytic ruthenium dioxide with sodium hypochlorite as co-oxidant, reducing reaction time from hours to minutes while improving yield to 92%.

Process economics indicate raw material costs constituting 68% of total production expense, with energy inputs accounting for 22% and waste treatment comprising 10%. Environmental impact assessment shows carbon efficiency of 47% with E-factor (mass of waste per mass of product) of 8.2. Major waste streams include inorganic salts from oxidation and neutralization steps, which are recovered and recycled where technically feasible.

Analytical Methods and Characterization

Identification and Quantification

High-performance liquid chromatography with ultraviolet detection provides primary quantification method using C18 reverse-phase column with mobile phase consisting of acetonitrile:water:phosphoric acid (45:55:0.1 v/v/v) at flow rate 1.0 mL·min^-1. Detection occurs at 275 nm with retention time 6.8 minutes and limit of quantification 0.05 mg·L^-1. Gas chromatography-mass spectrometry employing DB-5MS column (30 m × 0.25 mm × 0.25 μm) with temperature programming from 80°C to 280°C at 10°C·min^-1 provides confirmatory analysis with electron impact ionization at 70 eV.

Liquid chromatography-tandem mass spectrometry using electrospray ionization in negative mode achieves detection limits of 0.1 μg·kg^-1 in soil matrices. Characteristic multiple reaction monitoring transitions include m/z 212.9→196.9 (collision energy -18 eV) and m/z 212.9→168.9 (collision energy -25 eV) for quantification and confirmation respectively. Sample preparation involves accelerated solvent extraction with acetone:dichloromethane (1:1 v/v) at 100°C and 1500 psi followed by solid-phase extraction cleanup using graphitized carbon black cartridges.

Purity Assessment and Quality Control

Technical grade aminocyclopyrachlor specifications require minimum purity of 95.0% by HPLC area normalization with maximum individual impurity not exceeding 1.0%. Common impurities include 6-amino-2-cyclopropylpyrimidine-4-carboxylic acid (des-chloro analog, typically 0.3-0.8%), 5-chloro-2-cyclopropylpyrimidine-4-carboxylic acid (des-amino analog, typically 0.2-0.5%), and various cyclopropyl decomposition products. Moisture content specification requires less than 0.5% by Karl Fischer titration with residue on ignition not exceeding 0.1%.

Stability testing indicates shelf life exceeding 24 months when stored in high-density polyethylene containers at temperatures below 30°C. Accelerated stability testing at 54°C for 14 days shows less than 2% degradation, meeting international guidelines for pesticide stability. Compatibility testing demonstrates stability in common formulation vehicles including water, organic solvents, and various surfactant systems.

Applications and Uses

Industrial and Commercial Applications

Aminocyclopyrachlor serves primarily as a selective herbicide for professional vegetation management in non-crop areas. Applications include rights-of-way maintenance, utility line clearance, industrial site management, and turf management on golf courses and sod farms. The compound exhibits exceptional activity against broadleaf weeds including woody plants, with application rates typically ranging from 0.1 to 0.4 kg active ingredient per hectare.

Formulation technology typically employs soluble liquid concentrates containing 240-360 g active ingredient per liter, often combined with surfactants and deposition agents to enhance foliar retention and penetration. Market analysis indicates annual global production exceeding 500 metric tons with value chain comprising raw material suppliers, technical material producers, formulators, and distribution networks. Regulatory status varies by jurisdiction with major approvals in North America and selective authorizations in other regions.

Research Applications and Emerging Uses

Research applications utilize aminocyclopyrachlor as a model compound for studying auxin-mimicking mechanisms in plants. The compound serves as a molecular template for structure-activity relationship studies aiming to develop new herbicides with improved selectivity and environmental profiles. Recent investigations explore potential applications in plant physiology research, particularly studies of gene expression regulation in response to synthetic auxins.

Emerging research examines the compound's potential as a synthetic intermediate for pharmaceutical development, particularly as a building block for pyrimidine-containing therapeutic agents. Patent analysis indicates ongoing intellectual property development around derivative compounds with modified substitution patterns aimed at alternative biological activities. The compound's unique combination of functional groups makes it valuable for coordination chemistry studies, particularly with transition metals forming complexes through the carboxylic acid and amino groups.

Historical Development and Discovery

The development of aminocyclopyrachlor emerged from systematic herbicide discovery programs targeting improved auxin-mimicking agents with enhanced environmental persistence. Initial patent applications filed in 2005 disclosed the compound's synthesis and herbicidal activity, representing the culmination of structure-activity optimization efforts spanning nearly a decade. The discovery process involved iterative molecular design building upon the pyrimidine carboxylic acid scaffold previously identified in related compounds.

Key developmental milestones included optimization of the cyclopropyl substituent for improved soil persistence and substitution pattern refinement for selective phytotoxicity. Registration under the trade name Imprelis occurred in 2010 following extensive toxicological and environmental fate studies. Subsequent observations of non-target plant effects led to usage restrictions and enhanced label precautions, contributing to improved understanding of the compound's environmental behavior and plant sensitivity patterns.

Conclusion

Aminocyclopyrachlor represents a structurally sophisticated synthetic organic compound with significant scientific and commercial importance. The molecular architecture combines multiple functional groups in a conjugated pyrimidine system, creating distinctive electronic properties and reactivity patterns. The compound demonstrates moderate environmental persistence with complex degradation kinetics dependent on soil composition and climatic conditions. Physical properties including limited volatility and significant hydrogen bonding capacity influence formulation development and application methodologies.

Ongoing research continues to elucidate structure-activity relationships and environmental fate processes, contributing to improved understanding of auxin-mimicking compounds. Future development may focus on derivative compounds with modified substitution patterns aimed at alternative biological activities or improved environmental profiles. The compound serves as a valuable template for coordination chemistry studies and pharmaceutical intermediate synthesis, indicating potential expansion beyond agricultural applications. Continued investigation of degradation pathways and metabolic processes will further illuminate the compound's environmental behavior and ecological impacts.