Introduction
C15H11ClN2O2 is a chemical formula that denotes a molecule composed of fifteen carbon atoms, eleven hydrogen atoms, one chlorine atom, two nitrogen atoms, and two oxygen atoms. The molecular weight of this compound is 266.65 g·mol⁻¹. It represents a class of organic compounds that typically contain a heterocyclic scaffold, a halogenated aromatic ring, and functional groups such as amide or ester linkages. The presence of both chlorine and nitrogen atoms often imparts significant biological activity, making molecules with this formula relevant in pharmaceutical, agrochemical, and material science contexts.
The formula itself does not specify a unique structure; many isomeric compounds can share the same empirical composition. Nevertheless, literature surveys identify several representative molecules, including certain benzodiazepine derivatives, chlorinated phenylimidazoles, and chlorinated phenylpiperazines. These examples illustrate the structural diversity that can arise from the same elemental composition.
Structural Features
General Composition
The formula C15H11ClN2O2 indicates a moderate level of unsaturation. The double bond equivalents (DBE) can be calculated as follows:
DBE = C - H/2 + N/2 + 1 = 15 - 11/2 + 2/2 + 1 = 15 - 5.5 + 1 + 1 = 11.5
Since DBE must be an integer, the actual formula likely reflects a slight discrepancy due to a miscount in hydrogen atoms or the presence of a charged species. Assuming a neutral molecule, the DBE of 11 implies the presence of multiple rings and/or double bonds, consistent with aromatic heterocycles and halogenated aromatic rings found in medicinal chemistry.
Common Isomeric Structures
- Benzodiazepine core: A fused 1,4-benzodiazepine ring system commonly found in anxiolytic agents. Substituents at positions 1, 3, 4, 7, and 8 can include chlorine, methyl, and acyl groups, giving rise to molecules with the C15H11ClN2O2 formula.
- Chlorinated phenylimidazole: A benzene ring substituted with a chlorine atom attached to an imidazole moiety. The imidazole nitrogen atoms contribute to the nitrogen count, while a carbonyl group provides one of the oxygen atoms.
- Chlorinated phenylpiperazine: A piperazine ring fused to a chlorophenyl group. Hydroxyl or carbonyl substituents on the piperazine or phenyl ring account for the second oxygen atom.
- Chlorinated quinazolinone: A fused benzene–pyrimidine system with a chlorine atom on the benzene ring and a lactam carbonyl.
These skeletons illustrate how variations in substitution pattern and ring fusion can yield the same elemental formula while producing distinct chemical and pharmacological properties.
Physical and Chemical Properties
Melting and Boiling Points
For representative compounds, reported melting points (MP) range from 120 °C to 210 °C, while boiling points (BP) are typically above 400 °C, indicating significant thermal stability. For example, a 1,4‑benzodiazepine derivative with a chlorophenyl group has an MP of 172 °C and a BP of 410 °C when measured under reduced pressure. The high BP reflects strong intermolecular forces, including hydrogen bonding and π–π stacking within the aromatic system.
Solubility
Solubility in organic solvents is generally good; compounds dissolve readily in dichloromethane, acetone, and ethanol. In aqueous media, solubility is limited, with typical values below 0.5 mg mL⁻¹ at room temperature. The presence of polar functional groups such as carbonyl or amide groups can be exploited to increase aqueous solubility through salt formation or esterification.
Spectroscopic Signatures
Infrared (IR) spectra typically show characteristic absorption bands: a strong band near 1650 cm⁻¹ for the amide C=O stretch, a weaker band around 1550–1600 cm⁻¹ for N–H bending, and aromatic C=C stretches between 1450 and 1600 cm⁻¹. Chlorine substituents give rise to weak bands near 600–700 cm⁻¹ due to C–Cl stretching.
In nuclear magnetic resonance (NMR) spectroscopy, the aromatic protons appear as multiplets in the 7.0–8.5 ppm region. The chlorine-bearing aromatic carbon typically resonates at 120–140 ppm in the carbon-13 spectrum. Amide or imide protons are observed as broad singlets or multiplets in the 6–8 ppm range, depending on hydrogen bonding.
Mass spectrometry generally shows a molecular ion [M]⁺ at m/z 266. The chloride isotope pattern (³⁵Cl/³⁷Cl) yields a characteristic doublet with a 3:1 intensity ratio, confirming the presence of a single chlorine atom.
Synthesis
Industrial Synthesis
Large-scale production of C15H11ClN2O2 derivatives typically proceeds through multi-step processes that begin with inexpensive starting materials such as chlorobenzene or chlorobenzaldehyde. A common industrial route involves the following sequence:
- Formation of a chlorinated aromatic intermediate: Chlorobenzene undergoes nitration to produce chloronitrobenzene, which is then reduced to chlorobenzylamine.
- Construction of the heterocyclic core: The benzylamine reacts with a suitable diketone or β-ketoester under cyclization conditions to form the desired fused ring system.
- Oxidation and final functionalization: Oxidative steps introduce the required carbonyl or amide groups, while selective chlorination may be performed to place the chlorine at the correct position.
Key reagents include nitric acid for nitration, lithium aluminum hydride for reductions, and oxidizing agents such as sodium hypochlorite or hydrogen peroxide for final steps. Reaction conditions are optimized to maximize yield and minimize side products, with typical overall yields ranging from 20 % to 35 % across the entire sequence.
Laboratory Routes
Small-scale synthesis often utilizes a modular approach that allows for variation in substitution patterns. One laboratory protocol for a benzodiazepine derivative with the target formula involves:
- Synthesis of 2-chloro-5-nitrobenzaldehyde: Starting from chlorobenzene, the aldehyde is prepared via the Gattermann–Koch formylation using CO, HCl, and a Lewis acid catalyst (e.g., AlCl₃).
- Reduction to the amine: The nitro group is reduced with catalytic hydrogenation over Pd/C or with SnCl₂/HCl, yielding 2-chloro-5-aminobenzaldehyde.
- Condensation with a 2,4-dimethyl-1,3-diketone: The amine reacts with the diketone in acetic acid to form an imine intermediate.
The dihydro product is oxidized with Jones reagent (CrO₃/H₂SO₄) to generate the amide carbonyl, completing the structure.
Each step typically requires purification by recrystallization or chromatography, with yields at each stage ranging from 60 % to 80 %. The overall synthetic efficiency is thus higher than industrial processes, though scale limitations and hazardous reagents (e.g., chromium(VI) compounds) necessitate careful waste disposal.
Key Reagents and Conditions
- Halogenation: Chlorination of aromatic rings is frequently achieved with N-chlorosuccinimide (NCS) under mild heating.
- Acylation: Introduction of the carbonyl group is often accomplished via Friedel–Crafts acylation or acyl chloride formation followed by nucleophilic substitution.
- Cyclization catalysts: Lewis acids such as BF₃·Et₂O, TiCl₄, or ZnCl₂ facilitate ring closure reactions, especially in the formation of heterocycles containing nitrogen atoms.
- Redox control: The choice of oxidizing or reducing agents is guided by the need to preserve sensitive functional groups (e.g., avoid over-oxidation of amides).
Applications
Pharmacological Use
Compounds with the C15H11ClN2O2 composition have been evaluated as anxiolytic and anticonvulsant agents. The presence of a chlorophenyl group at position 7 on the benzodiazepine core enhances lipophilicity, facilitating blood–brain barrier penetration. Two marketed agents exhibit this formula:
- Chlordiazepoxide analogs: These exhibit moderate potency in animal models of anxiety, with inhibitory activity at the GABA_A receptor mediated through benzodiazepine binding sites.
- Imidazole-containing anticonvulsants: Chlorinated imidazoles demonstrate activity against seizure disorders, likely due to modulation of voltage-gated ion channels.
Pharmacokinetic studies reveal moderate oral bioavailability (~30 %) and a half-life of 3–5 h in rodent models. Metabolism primarily involves hepatic dechlorination and oxidative ring opening, producing metabolites that can be monitored using LC–MS techniques.
Analytical Applications
Because of their distinct chromatographic behavior and isotope pattern, molecules with a single chlorine atom are often used as internal standards in quantitative analyses of complex mixtures. In environmental monitoring, chlorinated heterocycles serve as markers for industrial effluents, allowing for the determination of pollution sources.
Other Uses
Beyond therapeutic applications, C15H11ClN2O2 derivatives find use as intermediates in the synthesis of dyes and pigments. Their ability to undergo photochemical reactions makes them candidates for photochromic materials. Additionally, certain chlorinated phenylimidazoles act as ligands in coordination chemistry, stabilizing metal centers for catalysis or electronic applications.
Safety and Handling
Hazards
These compounds are generally considered hazardous due to their halogenated nature and potential to form toxic metabolites. Primary hazards include:
- Flammability: Many derivatives are flammable liquids, with flash points ranging from 25 °C to 45 °C.
- Toxicity: Inhalation or ingestion can lead to central nervous system depression, gastrointestinal irritation, or, in severe cases, organ damage.
- Carcinogenic potential: Chlorinated aromatic compounds are sometimes classified as potential carcinogens, particularly with chronic exposure.
Appropriate personal protective equipment (PPE) such as lab coats, goggles, and gloves is mandatory. Work should be performed in a well-ventilated fume hood, and spill kits containing absorbent materials and neutralizing agents should be readily available.
Regulatory Status
Regulatory oversight varies by country and application. Pharmaceutical derivatives are subject to stringent controls under drug scheduling regulations. For instance, benzodiazepine derivatives with this formula are listed as Schedule IV substances in the United States, requiring controlled procurement and record-keeping. Agrochemical analogs may be classified under pesticide regulation, demanding adherence to safety data sheets (SDS) and labeling requirements.
Related Compounds
Structural Analogues
Analogues that differ by one functional group provide insight into structure–activity relationships. Substituting a chlorine atom with a fluorine atom typically increases metabolic stability while reducing lipophilicity. Replacing a carbonyl group with an ether linkage may diminish hydrogen bonding, altering receptor binding affinity. Systematic comparison of analogues informs the rational design of new therapeutics with improved safety profiles.
Metabolites
Metabolites of C15H11ClN2O2 derivatives often arise through hepatic cytochrome P450-mediated oxidation. Common metabolic transformations include hydroxylation of the aromatic ring, dechlorination, and N‑demethylation. These metabolites are frequently identified in pharmacokinetic studies using LC–MS/MS, and their presence is essential for evaluating drug safety and efficacy.
Research and Development
Recent Studies
Recent literature highlights investigations into the anti-inflammatory potential of chlorinated benzodiazepine analogs. In a 2020 study, a novel derivative exhibited significant inhibition of pro-inflammatory cytokine release in cultured macrophages, with an IC₅₀ value of 1.2 µM. Structural elucidation confirmed the C15H11ClN2O2 composition, and computational docking suggested binding to the IKKβ kinase active site.
Another 2021 investigation explored the use of a chlorinated phenylimidazole as a ligand for copper(II) complexes. The resulting coordination compound displayed enhanced catalytic activity in the oxidation of alcohols, demonstrating the versatility of the formula in material applications.
Future Directions
Ongoing research aims to leverage the chlorinated heterocyclic scaffold for targeted drug delivery. Strategies include the attachment of polyethylene glycol (PEG) chains to improve pharmacokinetics and the design of prodrug systems that release the active molecule under specific physiological conditions. Additionally, exploration of green chemistry approaches - such as solvent-free reactions, microwave-assisted synthesis, and catalytic systems employing earth-abundant metals - holds promise for reducing environmental impact while maintaining high product yields.
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