Abstract

Chlortoluron, systematically named N′-(3-chloro-4-methylphenyl)-N,N-dimethylurea, is a synthetic phenylurea compound with the molecular formula C₁₀H₁₃ClN₂O and molar mass of 212.68 g·mol⁻¹. This crystalline organic solid exhibits a melting point of 148 °C and demonstrates moderate lipophilicity with a log P value of 2.41. The compound belongs to the urea herbicide class and functions as a potent inhibitor of photosynthetic electron transport. Chlortoluron manifests characteristic spectroscopic properties including distinctive IR absorption bands at 3340 cm⁻¹ (N-H stretch), 1665 cm⁻¹ (C=O stretch), and 1540 cm⁻¹ (N-H bend). Its chemical behavior is governed by the urea functional group and aromatic chloro-substitution, resulting in specific reactivity patterns and stability characteristics under various environmental conditions.

Introduction

Chlortoluron represents a significant member of the phenylurea herbicide class, first developed and patented by E. I. du Pont de Nemours and Company in 1952 alongside related compounds monuron and diuron. As an organic compound featuring both aromatic and urea functional groups, chlortoluron exemplifies the structural principles underlying modern agrochemical design. The compound's systematic name, N′-(3-chloro-4-methylphenyl)-N,N-dimethylurea, precisely describes its molecular architecture consisting of a 3-chloro-4-methylphenyl group connected through a urea linkage to dimethylamine. This structural arrangement confers specific physicochemical properties that determine its biological activity and environmental behavior. Chlortoluron has been extensively studied for its herbicidal properties and serves as a model compound for understanding structure-activity relationships in phenylurea chemistry.

Molecular Structure and Bonding

Molecular Geometry and Electronic Structure

The chlortoluron molecule exhibits planar geometry around the urea functionality with partial double-bond character in the C-N bonds adjacent to the carbonyl group. The carbonyl carbon atom displays sp² hybridization with bond angles approximately 120° around the carbonyl functionality. The aromatic ring adopts typical benzene geometry with C-C bond lengths of 1.39 Å and C-Cl bond length of 1.74 Å. The urea group demonstrates resonance stabilization with the carbonyl oxygen participating in electron delocalization with the adjacent nitrogen atoms. The N-H bond length measures 1.01 Å while the C=O bond length is 1.23 Å, consistent with typical urea derivatives. Electronic distribution analysis reveals electron density accumulation around the oxygen atom (partial charge -0.42) and depletion around the carbonyl carbon (partial charge +0.32). The chlorine atom carries a partial negative charge of -0.15 while the methyl groups exhibit partial positive charges of +0.12 each.

Chemical Bonding and Intermolecular Forces

Chlortoluron exhibits multiple types of chemical bonding and intermolecular interactions. Covalent bonding predominates within the molecule with C-C, C-N, C-O, C-H, and C-Cl bonds forming the molecular framework. The urea functionality engages in strong hydrogen bonding through both donor (N-H) and acceptor (C=O) sites. The carbonyl oxygen serves as a hydrogen bond acceptor with hydrogen bond energy of approximately 25 kJ·mol⁻¹, while the N-H group acts as a hydrogen bond donor with energy of 29 kJ·mol⁻¹. Van der Waals forces contribute significantly to crystal packing with dispersion energy components estimated at 15 kJ·mol⁻¹. The molecular dipole moment measures 4.2 Debye, primarily oriented along the C=O bond vector. The chlorine substituent introduces a localized dipole moment of 1.8 Debye oriented perpendicular to the aromatic ring plane. These intermolecular forces collectively determine the compound's solubility characteristics and solid-state properties.

Physical Properties

Phase Behavior and Thermodynamic Properties

Chlortoluron presents as a white to off-white crystalline solid at room temperature with orthorhombic crystal structure belonging to space group P2₁2₁2₁. The compound melts sharply at 148 °C with enthalpy of fusion measuring 28.5 kJ·mol⁻¹. No polymorphic forms have been reported under standard conditions. The density of crystalline chlortoluron is 1.38 g·cm⁻³ at 25 °C. The compound sublimes appreciably at temperatures above 100 °C with sublimation enthalpy of 89 kJ·mol⁻¹. The heat capacity of solid chlortoluron follows the equation Cₚ = 125.6 + 0.217T J·mol⁻¹·K⁻¹ between 25 °C and 140 °C. The refractive index of crystalline material is 1.582 at 589 nm. Vapor pressure is negligible at ambient temperatures but reaches 0.12 Pa at 100 °C. The compound exhibits low volatility with Henry's law constant of 2.3 × 10⁻⁷ Pa·m³·mol⁻¹.

Spectroscopic Characteristics

Infrared spectroscopy reveals characteristic absorption bands at 3340 cm⁻¹ (N-H stretch), 2960 cm⁻¹ and 2870 cm⁻¹ (C-H stretch of methyl groups), 1665 cm⁻¹ (C=O stretch), 1540 cm⁻¹ (N-H bend), 1480 cm⁻¹ (aromatic C=C stretch), and 1090 cm⁻¹ (C-Cl stretch). Proton NMR spectroscopy in deuterated dimethyl sulfoxide shows signals at δ 2.20 ppm (3H, s, aromatic methyl), δ 2.85 ppm (6H, s, N-dimethyl), δ 6.40 ppm (1H, s, NH), δ 7.25 ppm (1H, d, J = 8.5 Hz, H-5), δ 7.45 ppm (1H, dd, J = 8.5, 2.5 Hz, H-6), and δ 7.80 ppm (1H, d, J = 2.5 Hz, H-2). Carbon-13 NMR displays signals at δ 18.5 ppm (aromatic methyl), δ 36.2 ppm (N-dimethyl), δ 118.5 ppm (C-2), δ 125.8 ppm (C-5), δ 129.4 ppm (C-6), δ 132.7 ppm (C-1), δ 137.2 ppm (C-4), δ 139.5 ppm (C-3), and δ 155.9 ppm (carbonyl carbon). UV-Vis spectroscopy shows absorption maxima at 244 nm (ε = 12,400 M⁻¹·cm⁻¹) and 280 nm (ε = 1,800 M⁻¹·cm⁻¹) in methanol solution. Mass spectrometry exhibits molecular ion peak at m/z 212 with characteristic fragments at m/z 197 [M-CH₃]⁺, m/z 169 [M-CON(CH₃)₂]⁺, and m/z 72 [H₂NCON(CH₃)₂]⁺.

Chemical Properties and Reactivity

Reaction Mechanisms and Kinetics

Chlortoluron undergoes hydrolysis under both acidic and basic conditions with distinct mechanisms. Acid-catalyzed hydrolysis proceeds via protonation of the carbonyl oxygen followed by nucleophilic attack by water with rate constant k = 3.2 × 10⁻⁵ s⁻¹ at pH 3 and 25 °C. Base-catalyzed hydrolysis involves hydroxide attack at the carbonyl carbon with rate constant k = 8.7 × 10⁻⁶ s⁻¹ at pH 9 and 25 °C. The compound demonstrates photochemical degradation under UV irradiation with quantum yield of 0.023 at 254 nm. Primary photodegradation pathways include dechlorination, N-demethylation, and ring hydroxylation. Thermal decomposition begins at 180 °C with activation energy of 120 kJ·mol⁻¹, producing 3-chloro-4-methylaniline and dimethylcarbamic acid as primary decomposition products. Oxidation with potassium permanganate in aqueous solution yields 3-chloro-4-methylbenzoic acid with second-order rate constant k₂ = 4.3 M⁻¹·s⁻¹ at 25 °C.

Acid-Base and Redox Properties

Chlortoluron exhibits very weak acidity with pKₐ of 15.2 for the N-H proton, reflecting the electron-withdrawing nature of the adjacent carbonyl group. The compound shows no basic character within the pH range 0-14 due to the inability of the carbonyl oxygen to protonate under aqueous conditions. Redox properties include irreversible oxidation at +1.25 V versus standard hydrogen electrode corresponding to one-electron oxidation of the aromatic ring. Reduction occurs at -1.85 V versus SHE involving two-electron reduction of the carbonyl group. The compound demonstrates stability in neutral and mildly acidic conditions but undergoes gradual decomposition in strongly basic media. No significant buffer capacity is observed within the physiologically relevant pH range. The electrochemical behavior indicates moderate electron affinity with electron transfer rate constant of 0.15 cm·s⁻¹ at glassy carbon electrode.

Synthesis and Preparation Methods

Laboratory Synthesis Routes

The primary synthetic route to chlortoluron involves reaction of 3-chloro-4-methylaniline with phosgene followed by treatment with dimethylamine. The first step employs phosgene solution in toluene at 0-5 °C to form the corresponding isocyanate intermediate with yield exceeding 95%. The intermediate isocyanate then reacts with dimethylamine in dichloromethane at room temperature to yield chlortoluron with overall yield of 85-90%. Purification is achieved through recrystallization from ethanol-water mixture, producing material with purity greater than 99%. Alternative routes include reaction of 3-chloro-4-methylphenylcarbamate with dimethylamine or transamination reactions of other phenylurea derivatives. The phosgene route remains preferred due to high regioselectivity, excellent yield, and minimal byproduct formation. Scale-up considerations include careful handling of phosgene, efficient gas scrubbing systems, and solvent recovery processes.

Analytical Methods and Characterization

Identification and Quantification

High-performance liquid chromatography with UV detection provides the primary analytical method for chlortoluron quantification using C18 reverse-phase columns with mobile phase consisting of acetonitrile-water (60:40 v/v) at flow rate 1.0 mL·min⁻¹. Detection occurs at 244 nm with retention time of 6.8 minutes and limit of detection of 0.05 mg·L⁻¹. Gas chromatography with mass spectrometric detection employs DB-5MS columns with temperature programming from 80 °C to 280 °C at 10 °C·min⁻¹, providing confirmation through molecular ion at m/z 212 and characteristic fragments. Capillary electrophoresis with UV detection at 214 nm using 50 mM borate buffer at pH 9.2 offers an alternative method with separation efficiency of 150,000 theoretical plates. Spectrophotometric methods based on diazotization and coupling reactions achieve detection limits of 0.1 mg·L⁻¹ but lack specificity compared to chromatographic techniques.

Purity Assessment and Quality Control

Pharmaceutical-grade chlortoluron must contain not less than 98.0% and not more than 102.0% of C₁₀H₁₃ClN₂O on dried basis. Common impurities include 3-chloro-4-methylaniline (limit 0.2%), monomethyl derivative (limit 0.3%), and symmetric N,N′-di(3-chloro-4-methylphenyl)urea (limit 0.5%). Determination of water content by Karl Fischer titration must not exceed 0.5%. Residue on ignition remains below 0.1%. Heavy metal content determined by atomic absorption spectroscopy must be less than 10 ppm. Chromatographic purity testing requires that no single impurity exceeds 0.5% and total impurities remain below 1.0%. Stability testing under accelerated conditions (40 °C, 75% relative humidity) demonstrates no significant degradation over 6 months. Shelf life under recommended storage conditions (room temperature, protected from light) exceeds 3 years.

Applications and Uses

Industrial and Commercial Applications

Chlortoluron serves primarily as a selective herbicide in cereal crop production, particularly for winter wheat and barley. Application rates typically range from 1.5 to 3.0 kg active ingredient per hectare depending on soil type and weed pressure. The compound controls broadleaf weeds including corn chamomile (Anthemis arvensis), common poppy (Papaver rhoeas), and common chickweed (Stellaria media), as well as grass weeds such as black-grass (Alopecurus myosuroides) and annual meadow-grass (Poa annua). Commercial formulations often combine chlortoluron with other herbicides including diflufenican and pendimethalin to broaden the spectrum of activity and mitigate resistance development. Global production estimates approach 5,000 metric tons annually with major manufacturing facilities in Europe and China. Market demand remains stable despite increasing regulatory scrutiny due to the compound's efficacy and favorable environmental profile compared to older herbicides.

Historical Development and Discovery

The discovery of chlortoluron originated from systematic herbicide research at E. I. du Pont de Nemours and Company during the early 1950s. The 1952 patent US 2602769 disclosed numerous phenylurea derivatives as potent herbicides, including the specific example of N′-(3-chloro-4-methylphenyl)-N,N-dimethylurea. This research built upon earlier observations that certain arylurea compounds exhibited plant growth regulatory effects. Chlortoluron entered commercial production in 1971 following extensive field trials demonstrating its effectiveness against problematic weeds in cereal crops. The 1980s witnessed expanded use throughout European agriculture coinciding with changes in farming practices toward earlier sowing dates. Regulatory reevaluation during the 1990s and 2000s led to improved formulations with reduced application rates and enhanced environmental safety profiles. The compound's mechanism of action as a photosystem II inhibitor was elucidated through biochemical studies during the 1970s, establishing the structural basis for its herbicidal activity.

Conclusion

Chlortoluron represents a well-characterized phenylurea herbicide with established synthetic methodology, comprehensive analytical protocols, and defined application parameters. Its molecular structure exemplifies the principles of bioactive compound design with optimized hydrophobicity, hydrogen bonding capacity, and electronic distribution. The compound's physicochemical properties, including moderate water solubility, soil adsorption characteristics, and environmental persistence, determine its behavior in agricultural systems. Ongoing research focuses on degradation pathways, metabolic products, and interactions with soil components to further understand its environmental fate. While regulatory pressures continue to shape the agrochemical landscape, chlortoluron maintains relevance through formulation improvements and integrated weed management strategies. The compound serves as a reference point for developing new herbicides with improved selectivity and reduced environmental impact.