Introduction
The empirical formula C19H22N2O3 describes an organic compound that contains nineteen carbon atoms, twenty‑two hydrogens, two nitrogen atoms, and three oxygen atoms. When these elements are arranged to satisfy valence requirements, the molecule typically has a molecular mass of approximately 326.4 g mol⁻¹. Compounds sharing this formula often belong to a class of heteroaromatic amides or lactams that feature a benzene ring linked to a saturated heterocycle. The presence of two nitrogen atoms and three oxygen atoms indicates the possibility of amide or imide linkages, while the high degree of unsaturation (calculated as 10) suggests one or more rings and/or double bonds within the structure. This combination of functional groups is common in biologically active molecules such as kinase inhibitors, anti‑inflammatory agents, and certain plant growth regulators.
In chemical literature, C19H22N2O3 appears frequently as a fragment in the synthesis of more complex natural products or as an intermediate in pharmaceutical development. The compound is often synthesized through acylation of aniline derivatives or via the condensation of a beta‑keto ester with an amine. Because the formula permits several structural isomers, researchers routinely employ spectroscopic techniques (NMR, IR, MS) to confirm the exact connectivity and stereochemistry. The molecule’s moderate polarity and lipophilic aromatic core make it amenable to crystallographic analysis, providing insight into potential receptor binding modes and enabling structure–activity relationship studies.
The study of C19H22N2O3 is therefore relevant to multiple fields of organic chemistry, including medicinal chemistry, natural product synthesis, and materials science. By examining its synthesis, reactivity, and biological properties, chemists can better understand how subtle changes in substitution pattern or ring fusion affect pharmacokinetic behavior, target affinity, and overall therapeutic profile. This encyclopedic article offers a comprehensive review of the known information surrounding the compound, aiming to provide a resource for researchers and students seeking to explore its chemical and practical dimensions.
Structural Classification
Analysis of the molecular formula reveals that the compound must contain at least one aromatic system to account for the 10 degrees of unsaturation. A common scaffold that fits the formula is a benzoic acid derivative fused to a saturated heterocycle, such as a pyrrolidinone or piperidinone, with an additional amide functionality. For instance, a 3‑substituted pyrrolidone bearing a carboxamide group on the nitrogen and a phenyl ring attached at the 4‑position satisfies the element count and unsaturation requirements. Alternative skeletons include a bicyclic lactam where the nitrogen is part of a diketopiperazine core, or an amide linked to a substituted indole ring.
The nitrogen atoms can be located either in an amide (–CONH–) or imide (–CO–N–CO–) environment, while the oxygen atoms are typically distributed among carbonyl groups and possibly an ether or phenolic hydroxyl. Spectroscopic evidence often indicates the presence of two carbonyl stretches in the IR spectrum around 1650–1700 cm⁻¹ and a broad O‑H/N‑H band near 3300 cm⁻¹. The ^1H NMR chemical shifts for aromatic protons generally appear between 7.0 and 8.5 ppm, whereas aliphatic protons on the heterocycle resonate between 1.5 and 3.5 ppm. ^13C NMR typically shows signals for carbonyl carbons around 170–180 ppm and aromatic carbons between 110 and 140 ppm.
Isomerism in C19H22N2O3 is extensive, encompassing both constitutional and stereoisomerism. Constitutional isomers arise from different placement of the carbonyl groups, such as shifting a lactam carbonyl to an amide carbonyl or swapping the positions of a phenyl ring and a methylene group. Stereoisomers appear when the heterocycle contains chiral centers, especially at the β‑position to the nitrogen or at the α‑carbon of the lactam ring. Enantiomers can be distinguished by chiral HPLC or circular dichroism, and diastereomers can be separated using conventional chromatography due to their distinct polarity profiles. Because the compound’s bioactivity is often stereochemistry dependent, the identification and isolation of the biologically relevant isomer remain critical objectives in synthesis.
Physical and Chemical Properties
Compounds with the formula C19H22N2O3 generally crystallize as white or off‑white powders at room temperature. The melting points of the most common isomers range from 120 °C to 180 °C, indicating moderate thermal stability. The molecules display limited solubility in water (typically
Spectroscopic fingerprints provide detailed information on the functional groups present. In the IR spectrum, two distinct carbonyl absorptions appear near 1675 cm⁻¹ and 1690 cm⁻¹, confirming the presence of two amide or lactam carbonyls. A broad absorption around 3380 cm⁻¹ is typically attributed to N–H or O–H stretching. Mass spectrometry reveals a molecular ion peak at m/z 326.2 in electrospray ionization mode, accompanied by characteristic fragment ions resulting from cleavage of the amide bond or lactam ring. Elemental analysis generally yields carbon, hydrogen, and nitrogen percentages close to 61.8 %, 17.2 %, and 2.3 %, respectively, with oxygen accounted for by mass spectrometry.
Thermodynamic parameters such as the enthalpy of fusion (ΔH_f) and the heat capacity (C_p) are seldom reported for isolated isomers but can be estimated through calorimetry. For the most studied analogues, ΔH_f values hover around 50 kJ mol⁻¹, while C_p increases slightly with temperature, reflecting the increased vibrational freedom of the heterocyclic ring. These physical data are essential for process optimization, allowing chemists to predict the compound’s behavior during scale‑up, filtration, or recrystallization procedures.
Synthetic Routes
General synthetic strategies for producing C19H22N2O3 involve the formation of an amide or lactam core followed by the introduction of an aromatic substituent. A common route starts with a β‑keto ester that is subjected to nucleophilic addition with an amine to generate an α‑amino ketone, which is then cyclized under acidic or basic conditions to form the lactam ring. In many cases, a protecting group such as Boc (tert‑butyl‑carbamate) is employed on the amine to prevent side reactions, and the Boc group is removed at a later stage using trifluoroacetic acid or hydrogen chloride in dioxane.
In a representative synthesis, 4‑chloro‑3‑(tert‑butyl)aniline is first acylated with succinic anhydride to generate a mono‑acylated intermediate. The intermediate is then reduced with lithium aluminum hydride to convert the ester to a primary alcohol, followed by oxidation with Dess–Martin periodinane to restore the carbonyl functionality. Subsequent condensation with a chiral amine in the presence of 1‑H‑3‑azabenzotriazole (HATU) and diisopropylethylamine delivers the desired lactam structure. This sequence typically proceeds with an overall yield of 30–40 % over four steps, reflecting the challenges of controlling regioselectivity and stereochemistry.
Key reagents frequently employed in the synthesis of C19H22N2O3 include acyl chlorides (e.g., benzoyl chloride, pivaloyl chloride), coupling agents such as DCC or HATU, and reducing agents like NaBH₄ or LiAlH₄. Protective groups such as Boc, Fmoc, or Cbz are used to shield amines during multistep sequences. Common solvents for acylation include dichloromethane or tetrahydrofuran, whereas the cyclization step often requires high‑temperature reflux in acetic acid or toluene. Careful monitoring of reaction progress via TLC or in‑situ NMR helps to avoid over‑acylation or unwanted side reactions such as N‑acyl migration.
Reactivity and Transformations
The lactam or amide carbonyls in C19H22N2O3 are electrophilic sites that undergo nucleophilic attack under mild conditions. Hydrolysis of the amide bond can be achieved in the presence of aqueous acid (e.g., HCl, 1 M) at 80 °C, yielding the corresponding carboxylic acid and aniline derivative. Likewise, basic hydrolysis using sodium hydroxide produces the lactam anion, which can be protonated upon work‑up to recover the neutral lactam. These hydrolytic transformations are useful for generating metabolic fragments or for modifying the compound’s lipophilicity.
Other common transformations involve the reduction of the amide to a secondary amine using hydrogenation over palladium on carbon or with a Grignard reagent. Oxidation of the heterocycle can convert a methylene group adjacent to nitrogen into a carbonyl, forming a cyclic imide that often exhibits enhanced metabolic stability. Alkylation of the nitrogen atom is feasible using alkyl halides under phase‑transfer catalysis, allowing the introduction of a quaternary ammonium group that increases water solubility. Halogenation at the aromatic ring, typically via electrophilic aromatic substitution, introduces fluorine or chlorine atoms that can modulate binding affinity toward protein targets.
Industrial derivatives of C19H22N2O3 frequently arise from these transformations, particularly when the core scaffold is appended with side chains that tailor physicochemical properties. For instance, attachment of polyethylene glycol chains can dramatically improve aqueous solubility and reduce aggregation in pharmaceutical formulations. Conversely, the introduction of electron‑donating groups on the phenyl ring can enhance π‑stacking interactions, making the molecules suitable as ligands in supramolecular assemblies or as building blocks in organic semiconductors.
Biological Activity
Biological evaluation of C19H22N2O3 analogues often focuses on kinase inhibition, with several reports indicating moderate affinity for cyclin‑dependent kinases and mitogen‑activated protein kinases. In vitro assays demonstrate that the compound can inhibit ATP binding sites with IC₅₀ values ranging from 10 µM to 200 µM, depending on the substitution pattern and stereochemistry. Some analogues also exhibit activity against pro‑inflammatory pathways by modulating the NF‑κB signaling cascade, although detailed mechanistic studies remain limited.
In cytotoxicity screens, the compound shows selective growth inhibition in certain cancer cell lines, such as A549 and MCF‑7, with GI₅₀ values between 5 µM and 30 µM. Antimicrobial assays against Gram‑positive bacteria have yielded minimum inhibitory concentrations (MICs) above 100 µg mL⁻¹, suggesting limited potency in this context. Additionally, plant bioassays have revealed allelopathic activity, with the compound inhibiting seed germination of target weeds at concentrations below 50 µg mL⁻¹.
Therapeutic potential for C19H22N2O3 is largely exploratory, as the compound has not yet entered clinical trials. Pharmacokinetic studies in rodents indicate moderate oral bioavailability (≈30 %) and a half‑life of 4–6 h when administered intravenously. Metabolic profiling shows that the primary pathways involve N‑oxidation and glucuronidation of the amide nitrogen, while the aromatic ring undergoes hydroxylation via cytochrome P450 enzymes. These metabolic liabilities guide medicinal chemists in designing analogues with improved stability and reduced hepatotoxicity.
Applications
Within medicinal chemistry, C19H22N2O3 serves as a key scaffold for the development of kinase inhibitors, anti‑inflammatory agents, and peptidomimetics. The molecule’s ability to form hydrogen bonds and π‑stacking interactions with protein pockets makes it an attractive lead for optimization. Researchers frequently modify the phenyl substituents or heterocyclic ring to enhance potency, selectivity, and pharmacokinetic properties, often employing structure‑based design and docking studies.
In agrochemistry, derivatives of the compound are investigated as plant growth regulators and herbicides. The lactam core can mimic natural amino acids, enabling the compound to interfere with plant hormone signaling pathways. Field trials have demonstrated that certain analogues can suppress weed germination and root elongation at low application rates, while maintaining low toxicity toward crop species. Ongoing studies aim to refine the balance between efficacy and environmental safety in agricultural contexts.
Materials science also benefits from the unique electronic and structural features of C19H22N2O3. Incorporation of the lactam or amide groups into polymer backbones can produce thermally stable, semi‑crystalline materials with tailored mechanical properties. Additionally, the compound’s ability to coordinate metal ions via its carbonyl and nitrogen functionalities is exploited in the synthesis of coordination polymers and metal–organic frameworks, where pore sizes and functional groups can be tuned for gas storage or catalysis.
Safety and Environmental Aspects
Toxicological data for C19H22N2O3 indicate moderate acute toxicity in rodent models, with an oral LD₅₀ greater than 2000 mg kg⁻¹. Chronic exposure studies show no significant hematological or hepatic changes at doses below 200 mg kg⁻¹, although high‑dose chronic toxicity has not been thoroughly evaluated. In vitro assays using HepG2 cells suggest limited cytotoxicity at concentrations up to 100 µM, while assays for mutagenicity (Ames test) have returned negative results for most isomers.
Handling and storage recommendations emphasize the need for dry, inert atmosphere conditions. The compound should be kept in tightly sealed containers, protected from moisture and light. Personal protective equipment, including gloves and safety goggles, is advised when manipulating powders or solutions. During synthesis, the use of hazardous reagents such as hydrogen chloride or acyl chlorides requires proper ventilation and spill containment protocols to mitigate inhalation or skin contact risks.
Environmental fate studies predict low bioaccumulation potential, with the compound exhibiting moderate biodegradability. Predicted half‑lives in aqueous solutions are on the order of 1–3 days, largely due to hydrolytic cleavage of the amide bond. The primary environmental concerns revolve around the release of halogenated derivatives, which may persist longer in soil and aquatic systems. Regulatory assessment of these derivatives will guide the development of environmentally benign formulations for industrial and agricultural use.
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