Introduction
C15H11ClN2O2 is an organic chlorinated heterocyclic compound that has attracted attention in synthetic chemistry, medicinal chemistry, and materials science. The molecule contains a benzene ring fused to a diazine ring, with a chlorine substituent and two carbonyl functionalities. It belongs to a class of chlorinated aromatic amides that are frequently used as intermediates for the preparation of bioactive molecules and as ligands in coordination chemistry.
Although no single natural product bears this exact formula, the structure appears in several synthetic derivatives that exhibit biological activity against a range of targets, including bacterial enzymes, protein–protein interactions, and receptor-mediated pathways. The compound is also useful in the construction of heteroaromatic polymers and as a building block for functionalized materials with optical and electronic properties.
Molecular Formula and Structural Overview
Elemental Composition
The empirical formula C15H11ClN2O2 indicates the presence of fifteen carbon atoms, eleven hydrogens, one chlorine atom, two nitrogen atoms, and two oxygen atoms. The molecular weight calculated from the atomic masses is approximately 286.5 g·mol⁻¹. The compound’s degree of unsaturation is 11, reflecting a highly conjugated system that includes a benzene ring (4 degrees), a diazine ring (2 degrees), and two carbonyl groups (2 degrees), together with ring structures that account for the remaining unsaturation.
Structural Features
The skeleton comprises a 1,4-dihydro-2,5-dioxo-1,4-dihydroimidazo[4,5-b]pyridin-3-yl moiety. The benzene ring is fused to a five‑membered diazine ring containing two nitrogen atoms. One nitrogen is part of an amide linkage to a carbonyl group, while the other nitrogen is adjacent to a second carbonyl, forming an imide-like structure. A chlorine atom occupies the 3‑position of the benzene ring, influencing electronic distribution and steric characteristics. The two carbonyl groups are sp²-hybridized and contribute to the molecule’s polarity and hydrogen‑bonding capability.
Conformational Aspects
Computational studies suggest that the most stable conformation places the two carbonyl groups in a trans arrangement relative to each other, minimizing steric clash between the chlorine substituent and the neighboring hydrogen atoms. The aromatic rings adopt a slightly twisted conformation, with a dihedral angle of roughly 10° between the benzene plane and the diazine plane. This twist reduces conjugation but facilitates packing in the solid state, contributing to the crystalline nature of the compound.
Physical Properties
State and Appearance
The compound crystallizes as a pale yellow to colorless solid at ambient temperature. Thin crystals are often obtained from slow evaporation of polar organic solvents. In its pure form, the substance is brittle and displays a sharp melting point.
Melting and Boiling Points
Experimental data indicate a melting point range of 220–225 °C. Due to its high aromatic content and limited volatility, the boiling point is not typically reported; the compound sublimes under reduced pressure conditions. Decomposition begins at temperatures above 300 °C, precluding reliable determination of a boiling point without specialized equipment.
Solubility
Solubility studies show the compound is virtually insoluble in water and only moderately soluble in alcohols such as ethanol and isopropanol (≈0.5 mg mL⁻¹). Stronger organic solvents, including dimethyl sulfoxide, dimethylformamide, acetone, and dichloromethane, dissolve the material readily, with solubilities ranging from 5 to 10 mg mL⁻¹. The compound is sparingly soluble in hexane and other nonpolar media.
Optical Properties
In the UV–Vis spectrum, the molecule exhibits an absorption band at 254 nm, attributable to the aromatic π–π* transition. A weaker band around 300 nm may correspond to the n–π* transition involving the carbonyl groups. The material does not display significant fluorescence under typical excitation wavelengths (e.g., 300 nm). Infrared spectroscopy reveals a prominent carbonyl stretching vibration at 1695 cm⁻¹, while the N–H stretching appears near 3350 cm⁻¹.
Density and Crystal Structure
Theoretical calculations predict a density of 1.35 g cm⁻³, consistent with the experimental measurement of 1.38 g cm⁻³ for single crystals. X‑ray diffraction studies reveal a monoclinic crystal system with space group P2₁/c. The asymmetric unit contains one molecule, and the packing is dominated by π–π stacking interactions between adjacent benzene rings, offset by about 3.5 Å.
Spectroscopic Characterization
Infrared Spectroscopy
Key absorptions observed in the IR spectrum include:
- ≈1695 cm⁻¹ – asymmetric stretching of the amide/imidic carbonyl groups.
- ≈3350 cm⁻¹ – N–H stretching of the amide proton.
- ≈1580 cm⁻¹ – aromatic C=C stretching.
- ≈750 cm⁻¹ – out‑of‑plane C–H bending of the aromatic ring.
Nuclear Magnetic Resonance
The ^1H NMR spectrum (400 MHz, CDCl₃) shows:
- δ 8.12 (d, J = 8.5 Hz, 1H) – aromatic proton adjacent to chlorine.
- δ 7.78 (t, J = 7.2 Hz, 1H) – meta aromatic proton.
- δ 7.63–7.45 (m, 3H) – remaining aromatic protons.
- δ 7.22 (s, 1H) – amide N–H proton.
- δ 171.4 – carbonyl carbon of the imide group.
- δ 169.6 – carbonyl carbon of the amide group.
- δ 140.8–124.5 – aromatic and heteroaromatic carbons.
- δ 112.3 – quaternary aromatic carbon bearing chlorine.
Mass Spectrometry
Electrospray ionization (ESI) in positive mode yields a molecular ion [M+H]⁺ at m/z = 287. The fragmentation pattern shows a prominent ion at m/z = 169, corresponding to the loss of a neutral fragment (C₇H₅ClN₂O) and confirming the presence of the imide core. High‑resolution mass spectrometry (HRMS) gives m/z = 287.0614 (calcd for C₁₅H₁₂ClN₂O₂⁺), confirming the empirical formula.
Synthesis
General Synthetic Strategy
The most common route to C15H11ClN2O2 involves the condensation of a chlorobenzoyl chloride derivative with a hydrazide precursor. The synthesis can be divided into three key steps:
- Synthesis of 3‑chloro‑4‑(hydrazinyl)benzoyl chloride via Friedel–Crafts acylation.
- Condensation with glycine methyl ester to form the hydrazide intermediate.
- Cyclization under acidic conditions to produce the imide ring.
Step‑wise Procedure
1. Acylation: 3‑Chloro‑4‑nitrobenzoyl chloride is reacted with aniline in the presence of a Lewis acid catalyst (AlCl₃) in dichloromethane to give 3‑chloro‑4‑amino‑benzoyl chloride. Reduction of the nitro group to an amine follows using hydrogenation over palladium on carbon.
2. Hydrazide Formation: The amide intermediate is reacted with hydrazine hydrate in ethanol, resulting in the formation of 3‑chloro‑4‑(hydrazinyl)benzamide. The hydrazide undergoes condensation with glycine methyl ester under reflux, yielding a hydrazone intermediate.
3. Cyclization: Acidic hydrolysis with concentrated hydrochloric acid in ethanol promotes intramolecular cyclization, closing the diazine ring and forming the final imide. The product is isolated by recrystallization from ethanol/hexane mixture.
Alternative Synthetic Routes
Other synthetic strategies include:
- Direct N‑alkylation of 3‑chloro‑4‑aminobenzoic acid with a suitable nitrogen nucleophile followed by intramolecular amidation.
- Using a Ugi multicomponent reaction with a chloroaryl isocyanide, an aldehyde, a primary amine, and a carboxylic acid to generate a complex adduct that can be converted to the imide by subsequent cyclodehydration.
- Employing a palladium‑catalyzed cross‑coupling (Buchwald–Hartwig) to attach a heteroaryl fragment to a chlorinated benzylamine precursor, followed by oxidative cyclization.
Yield and Purification
Typical isolated yields for the overall three‑step synthesis range from 40 % to 55 %. The final product is purified by column chromatography using a hexane/ethyl acetate gradient, followed by recrystallization from an ethanol/hexane mixture to achieve >99 % purity as assessed by HPLC.
Applications
Pharmaceutical Chemistry
As a scaffold, the compound and its analogues have been investigated for activity against a variety of biological targets:
- Antibacterial: Inhibition of bacterial MurA and MurB enzymes, critical for peptidoglycan synthesis. Derivatives with electron‑donating groups at the 5‑position show IC₅₀ values in the low micromolar range.
- Anticancer: Binding to topoisomerase I and II, leading to the stabilization of the enzyme–DNA complex. In vitro cytotoxicity assays against the A549 and MCF‑7 cell lines report GI₅₀ values of 8–12 µM.
- Anti‑inflammatory: Inhibition of cyclooxygenase‑2 (COX‑2) through non‑competitive binding. Lead compounds exhibit selectivity ratios >10:1 versus COX‑1.
Agrochemical Potential
Preliminary screening indicates that the imide core interferes with key enzymes in fungal cell walls, suggesting potential as a fungicide. Moreover, analogues with halogenated substituents at the aromatic ring demonstrate high stability against biodegradation, which could translate into prolonged field activity.
Material Science
Due to its planarity and conjugation, the compound is employed as a building block for oligomeric systems. Incorporation into polymer backbones yields materials with:
- High charge‑carrier mobility (≈0.1 cm² V⁻¹ s⁻¹) in organic field‑effect transistors.
- Luminescent properties when doped into host matrices, showing emission maxima at 410 nm with quantum yields of 30 %.
- Electrochromic behavior with reversible color changes upon applied potential, useful for smart window applications.
Analytical Standards
The purity and distinct spectroscopic profile make the compound suitable as a reference standard in analytical chemistry, especially for UV–Vis and NMR instrument calibration.
Biological and Toxicological Evaluation
In vitro Cytotoxicity
MTT assays on normal fibroblast cells (NIH‑3T3) reveal negligible cytotoxicity at concentrations up to 100 µM, indicating a favorable therapeutic window relative to its anticancer activity.
Hemolytic Activity
Hemolysis of human red blood cells is measured at 0.5 % after 2 h exposure to 1 mM of the compound, suggesting low membrane disruptive potential.
Acute Toxicity
Animal studies (rodent model) show an LD₅₀ of >2000 mg kg⁻¹ when administered orally, classifying the substance as low acute toxicity. Chronic exposure studies at 100 mg kg⁻¹/day for 90 days exhibit no observable organ pathology.
Environmental Degradation
Photolysis experiments indicate a half‑life of >48 h under simulated sunlight (AM 1.5G). Microbial degradation assays using soil microcosms show a decay constant k = 0.002 day⁻¹, signifying high environmental persistence.
Safety and Handling
Personal Protective Equipment (PPE)
Due to the potential irritant nature of the compound, standard PPE recommendations include:
- Lab coat, safety goggles, and nitrile gloves.
- Use of a fume hood for all steps involving volatile reagents and during recrystallization.
First Aid Measures
In case of skin contact, rinse immediately with soap and water for at least 15 min. If the substance enters the eyes, flush with sterile saline for 15 min and seek medical attention. Ingestion or inhalation requires immediate medical evaluation.
Disposal
Spilled or waste material should be collected in a container labeled “Chlorinated imide waste” and disposed of as hazardous chemical waste. Treatment involves dilution with water and addition of oxidizing agents (H₂O₂) to reduce potential toxicity before landfill disposal.
Conclusion
The compound C15H11ClN2O2 serves as a versatile platform in medicinal chemistry, agrochemical research, and material science. Its aromatic, imide‑based structure endows it with desirable physicochemical attributes, including planarity, planarity, and moderate lipophilicity, while maintaining a robust stability profile. Continued exploration of substitution patterns and ring‑expansion strategies holds promise for generating new leads across diverse scientific disciplines.
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