5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole: Properties & Uses
5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole: Properties & Uses
5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole is a synthetic heterocyclic compound featuring a five-membered 1,2,4-oxadiazole ring substituted with a cyclohexyl group at the 5-position and a 4-nitrophenyl group at the 3-position, making it a versatile building block in medicinal and synthetic chemistry research.
- Chemical Name
- 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole
- SKU / Catalog Number
- C185130
- Ring System
- 1,2,4-Oxadiazole (five-membered aromatic heterocycle containing one oxygen and two nitrogen atoms)
- Key Substituents
- Cyclohexyl at C-5; 4-nitrophenyl at C-3
- Molecular Formula
- C14H15N3O3
- Primary Research Use
- Synthetic intermediate and pharmacophore scaffold in drug discovery and heterocyclic chemistry
Chemical Structure and Key Physicochemical Features
5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole belongs to the 1,2,4-oxadiazole family of five-membered aromatic heterocycles. The ring contains one oxygen atom at position 1 and two nitrogen atoms at positions 2 and 4, conferring pronounced electron-deficient character and metabolic stability relative to non-aromatic analogues.
The 4-nitrophenyl substituent at C-3 introduces strong electron-withdrawing character through both inductive and resonance effects, lowering the electron density of the oxadiazole ring and increasing the compound's electrophilic reactivity. The cyclohexyl group at C-5 provides lipophilic bulk and conformational rigidity that can influence membrane permeability and protein-binding geometry.
Together, the two substituents create a molecule with a balanced polar/nonpolar profile. The nitro group acts as a handle for further synthetic transformations—reduction to an amine, for example—making this compound useful as an intermediate in multi-step synthesis programs.
Note: Precise physical constants (melting point, logP, solubility) for this specific compound are not included in the available source material and should be confirmed from the product certificate of analysis or peer-reviewed literature before use in formal reports.
Synthesis and Reaction Chemistry of 1,2,4-Oxadiazoles
The 1,2,4-oxadiazole ring is most commonly assembled via the condensation of an amidoxime with an activated acyl equivalent. In a classical route, an aromatic nitrile bearing the nitrophenyl group is converted to the corresponding amidoxime by reaction with hydroxylamine. The amidoxime is then cyclized with a carboxylic acid derivative—such as cyclohexanecarbonyl chloride or cyclohexanecarboxylic acid activated with a coupling agent—under thermal or base-mediated conditions to close the ring and furnish the 3,5-disubstituted 1,2,4-oxadiazole.
Alternative strategies include the use of nitrile oxides with nitriles (1,3-dipolar cycloaddition), or the reaction of hydroxamic acids with orthoesters. The choice of route depends on the availability of starting materials, required scale, and functional-group tolerance needed in the specific synthesis program.
Once formed, the 1,2,4-oxadiazole ring is notably stable to hydrolysis under mildly acidic or basic aqueous conditions, which distinguishes it from the isomeric 1,3,4-oxadiazole and makes it attractive as a metabolically robust bioisostere for ester or amide bonds in drug candidates.
Review flag: Specific reaction conditions, yields, and literature citations for the synthesis of this exact compound have not been identified in the source material and require verification.
Research and Drug Discovery Applications
The 1,2,4-oxadiazole scaffold is well-established in medicinal chemistry as a bioisostere for amide and ester linkages. Its aromatic character and metabolic resistance make it attractive for incorporation into drug candidates where hydrolytic instability of an amide or ester would limit pharmacological utility. Compounds bearing this heterocycle have been explored across diverse therapeutic areas including antibacterial, antifungal, antiparasitic, anti-inflammatory, and anticancer research programs.
5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole is of interest as a research reagent and synthetic intermediate. The 4-nitrophenyl group provides a chromophore useful in UV-based assays, and the nitro functionality can be selectively reduced to a primary amine, enabling further elaboration via acylation, reductive amination, or formation of diazonium salts for coupling chemistry. The cyclohexyl group introduces sp3 carbon character, which is associated with improved aqueous solubility and reduced crystal packing compared to purely aromatic analogues—a property increasingly valued in fragment-based drug discovery.
In target-engagement studies, structurally related nitrophenyl-oxadiazoles have been used as tool compounds or as reference standards in enzyme inhibition assays. Researchers should consult the primary literature for specific biological activity data relevant to their assay systems.
Review flag: No specific biological activity data for C185130 are present in the source material. Claims about therapeutic activity require primary literature support before inclusion in formal documents.
Handling, Storage, and Laboratory Safety Guidance
As with all research-grade nitroaromatic heterocycles, appropriate laboratory safety practices should be followed when handling 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole. Researchers should consult the product Safety Data Sheet (SDS) prior to use to confirm hazard classifications, recommended personal protective equipment (PPE), and first-aid measures specific to this compound.
General precautions for nitroaromatic compounds include working in a well-ventilated fume hood, wearing appropriate gloves, lab coat, and eye protection. Avoid generating fine dusts or aerosols. Incompatibilities typical of nitroaromatics—such as strong reducing agents and open flames—should be considered during storage and disposal planning.
For storage, keep the compound in a tightly sealed container, away from light, heat, and moisture, at the temperature specified on the product label or certificate of analysis. Many solid organic heterocycles are stable at room temperature when kept dry and away from light, but precise storage conditions for C185130 should be confirmed from the Aladdin Scientific product page or SDS.
Review flag: Specific hazard classifications, GHS pictograms, storage temperature, and flash point for C185130 are not available in the source material provided. These must be sourced from the official SDS before publication.
Frequently asked questions
What is the significance of the 1,2,4-oxadiazole ring in drug discovery?
The 1,2,4-oxadiazole ring is valued in drug discovery as a bioisostere for amide and ester bonds. Its aromatic stability confers resistance to metabolic hydrolysis, potentially improving the pharmacokinetic profile of drug candidates compared to their amide or ester counterparts. It also provides a defined geometry and electron-deficient character that can optimize binding interactions with protein targets.
How can the nitro group of this compound be used in further synthetic transformations?
The 4-nitrophenyl group can be selectively reduced to a primary aniline using standard conditions such as catalytic hydrogenation (Pd/C, H₂) or chemical reduction (e.g., iron/acetic acid, SnCl₂). The resulting amine serves as a versatile handle for acylation, sulfonylation, reductive amination, or diazotization, enabling the synthesis of more complex derivatives from this intermediate.
What solvent systems are recommended for dissolving 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole in laboratory assays?
Polar aprotic solvents such as DMSO or DMF are generally suitable for dissolving lipophilic nitroaromatic heterocycles and are compatible with most biochemical assay formats when used at low concentrations (typically ≤0.1% v/v final). Chlorinated solvents (DCM, chloroform) or ethyl acetate are typically appropriate for synthetic work. Exact solubility data for this compound should be confirmed experimentally or from the product SDS/CoA before use.
Is 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole (C185130) available from Aladdin Scientific?
Yes. 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole is available from Aladdin Scientific under catalog number C185130. For current pricing, pack sizes, purity specifications, and availability, please visit the Aladdin Scientific product page or contact customer support.
References
- Kaur R, Silakari O. A review on 1,2,4-oxadiazole as bioisostere of amides and esters in drug discovery. Mini Rev Med Chem. General reference—specific volume and page not confirmed from source material.
- Pace A, Buscemi S, Piccionello AP. 1,2,4-Oxadiazoles: synthesis and applications. Adv Heterocycl Chem. General reference—specific volume, page, and year not confirmed from source material.
- Aladdin Scientific. Product page: 5-Cyclohexyl-3-(4-nitrophenyl)-1,2,4-oxadiazole, SKU C185130. Aladdin Scientific Co., Ltd.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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