3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride
[CAS# 25629-50-9]

Identification

• Classification: Chemical reagent >> Organic reagent >> Acid halide
• Name: 3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride
• Synonyms: 3-(2-Chlorophenyl)-5-methyl-1,2-oxazole-4-carbonyl chloride
• Molecular Formula: C₁₁H₇Cl₂NO₂
• Molecular Weight: 256.09
• CAS Registry Number: 25629-50-9
• EC Number: 247-137-4
• SMILES: CC1=C(C(=NO1)C2=CC=CC=C2Cl)C(=O)Cl

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 41 - 42 ºC (Expl.)
• Boiling point: 381.7±42.0 ºC 760 mmHg (Calc.)^*
• Flash point: 184.6±27.9 ºC (Calc.)^*
• Index of refraction: 1.574 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H314-H317-H319
• Precautionary Statements: P260-P261-P264-P264+P265-P272-P280-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P351+P338-P305+P354+P338-P316-P321-P333+P317-P337+P317-P362+P364-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Skin corrosion	Skin Corr.	1	H314
Eye irritation	Eye Irrit.	2	H319
Skin corrosion	Skin Corr.	1B	H314

Discovory and Applicatios

3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride is a synthetic compound derived from the isoxazole heteroaromatic scaffold. Isoxazoles are five-membered heterocycles containing both nitrogen and oxygen, known for their broad reactivity and incorporation into numerous biologically active molecules. The compound consists of a substituted isoxazole ring bearing a 2-chlorophenyl substituent at the 3-position, a methyl group at the 5-position, and a reactive carbonyl chloride functional group at the 4-position. This specific arrangement makes the compound a valuable intermediate in organic synthesis.

The historical background of compounds of this type lies in the development of isoxazole chemistry during the late 19th and early 20th centuries, when methods for constructing isoxazole rings were established. These included the condensation of hydroxylamine with diketones and the 1,3-dipolar cycloaddition of nitrile oxides with alkynes, which provided versatile access to substituted isoxazoles. The incorporation of phenyl and substituted phenyl groups, such as chlorophenyl, expanded the chemical diversity of this class. Researchers quickly recognized that functional groups like carbonyl chlorides could be introduced onto isoxazole rings, thereby enabling further synthetic elaboration.

The carbonyl chloride functional group in 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride confers significant reactivity, particularly in acylation reactions. It readily reacts with nucleophiles, including amines, alcohols, and thiols, to form amides, esters, and thioesters. This reactivity has made such compounds useful as intermediates in the preparation of more complex molecules. Because the isoxazole moiety is a privileged structure in medicinal chemistry, being found in various drugs such as certain anti-inflammatory and antimicrobial agents, derivatives of this compound have been investigated in drug discovery efforts.

In medicinal chemistry, isoxazole-based carbonyl chlorides like this one have been applied in the synthesis of novel amide-linked scaffolds. The introduction of a 2-chlorophenyl substituent can influence both electronic and steric properties, potentially enhancing biological activity in target compounds. The compound’s ability to act as a versatile acylating agent makes it an attractive building block for generating diverse analogues for pharmacological evaluation. Its incorporation into synthetic schemes has enabled researchers to explore new derivatives with potential therapeutic relevance.

Beyond pharmaceutical applications, such compounds have also been used in the preparation of functionalized intermediates for agrochemical development and materials science. Isoxazole derivatives with acyl chloride functionalities can participate in step-growth polymerizations or cross-linking reactions, creating novel polymers with heteroaromatic character. The presence of a chloro-substituted phenyl group can further modify the chemical and physical properties of the final material.

From a chemical perspective, the compound requires careful handling due to the high reactivity of the carbonyl chloride group. It is prone to hydrolysis upon exposure to moisture, yielding the corresponding carboxylic acid. For this reason, reactions are typically carried out under anhydrous conditions and often involve in situ use of the acyl chloride to minimize decomposition. The compound’s stability is also influenced by the electron-withdrawing effect of the 2-chlorophenyl substituent, which can affect both reactivity and storage requirements.

Although 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride is not a final product with direct industrial or medical application, its importance lies in its function as a synthetic intermediate. By enabling the preparation of complex derivatives, it contributes to ongoing research in multiple chemical fields. The compound exemplifies how functionalized heterocycles serve as versatile platforms for advancing both fundamental and applied chemistry.

References

2022. Design, Synthesis, and Insecticidal Activity of Novel Diacylhydrazine Derivatives Containing an Isoxazole Carboxamide or a Pyridine Carboxamide Moiety. Russian Journal of General Chemistry, 92(1).
DOI: 10.1134/s1070363222010182

2017. Synthesis, biological evaluation, molecular docking, and ADMET studies of some isoxazole-based amides. Medicinal Chemistry Research, 26(12).
DOI: 10.1007/s00044-017-2070-z

2003. Cloxacillin. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-03-0229