5-Methyl-3-phenylisoxazole-4-carbonyl chloride
[CAS# 16883-16-2]

Identification

• Classification: Chemical reagent >> Organic reagent >> Acid halide
• Name: 5-Methyl-3-phenylisoxazole-4-carbonyl chloride
• Molecular Formula: C₁₁H₈ClNO₂
• Molecular Weight: 221.64
• CAS Registry Number: 16883-16-2
• EC Number: 240-915-4
• SMILES: CC1=C(C(=NO1)C2=CC=CC=C2)C(=O)Cl

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 24 - 25 ºC (Expl.)
• Boiling point: 371.9±30.0 ºC 760 mmHg (Calc.)^*
• Flash point: 178.7±24.6 ºC (Calc.)^*
• Index of refraction: 1.563 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05 Danger
• Hazard Statements: H314
• Precautionary Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin sensitization	Skin Sens.	1	H317
Serious eye damage	Eye Dam.	1	H318

Discovory and Applicatios

5-Methyl-3-phenylisoxazole-4-carbonyl chloride is a synthetic chemical compound that belongs to the class of isoxazole derivatives. Isoxazoles are five-membered heteroaromatic rings containing both nitrogen and oxygen atoms, and their derivatives have been extensively studied since the early 20th century for their chemical reactivity and biological activities. The specific derivative 5-methyl-3-phenylisoxazole-4-carbonyl chloride is a functionalized isoxazole that incorporates a carbonyl chloride group, making it a reactive intermediate of interest in organic synthesis.

The development of isoxazole derivatives can be traced back to foundational work in heterocyclic chemistry, when systematic studies of isoxazole ring systems were undertaken in the late 19th and early 20th centuries. Researchers discovered multiple synthetic routes to isoxazoles, including the condensation of hydroxylamine derivatives with diketones and the 1,3-dipolar cycloaddition of nitrile oxides with alkynes. These strategies facilitated the preparation of a wide variety of substituted isoxazoles, among them phenyl-substituted derivatives. The presence of both electron-donating and electron-withdrawing groups on the isoxazole ring was shown to significantly influence chemical reactivity and potential applications.

The compound 5-methyl-3-phenylisoxazole-4-carbonyl chloride functions primarily as a synthetic intermediate. The carbonyl chloride group is highly reactive toward nucleophiles such as amines, alcohols, and thiols, making it suitable for the preparation of amides, esters, and thioesters. For this reason, such derivatives have been used in the construction of more complex organic molecules, including pharmacologically active compounds. Isoxazole-based scaffolds are present in a variety of biologically active substances, including some non-steroidal anti-inflammatory drugs and agrochemical agents. The 5-methyl-3-phenylisoxazole-4-carbonyl chloride moiety has thus been explored in medicinal chemistry as a building block for novel analogues.

Applications of this compound are found mainly in the context of chemical synthesis. In pharmaceutical research, it has been employed in the preparation of amide-linked molecules where the isoxazole ring system contributes structural rigidity and aromatic character to the final compound. Its reactivity allows for the introduction of diverse substituents, expanding the chemical space available for drug discovery. In addition to medicinal chemistry, isoxazole derivatives bearing acyl chloride functionalities have also been studied in the context of polymer synthesis, where they can participate in step-growth polymerization reactions to yield functional materials.

From a chemical standpoint, the compound’s utility is closely tied to the reactivity of its carbonyl chloride group. This functional group is prone to hydrolysis in the presence of moisture, producing the corresponding carboxylic acid, and must therefore be handled under controlled conditions. In synthetic protocols, it is commonly used in situ for coupling reactions, often under mild conditions with the assistance of base catalysts or coupling agents. Its reactivity provides a route to functional derivatives that retain the isoxazole core, which can then be evaluated for physical, chemical, or biological properties.

Although 5-methyl-3-phenylisoxazole-4-carbonyl chloride is not known to have direct therapeutic or industrial applications on its own, its importance lies in its role as an intermediate. Through its incorporation into larger molecular frameworks, it contributes to the development of compounds with potential pharmaceutical, agrochemical, or materials applications. The study of such intermediates highlights the central role of reactive functional groups in synthetic organic chemistry and the continued exploration of heteroaromatic scaffolds as versatile building blocks.

References

1985. A method of quality control of 3-phenyl-5-methylisoxazole-4-carbonic acid chloranhydride using high performance liquid chromatography. Antibiotiki i meditsinskaia biotekhnologiia, 30(3).
URL: https://pubmed.ncbi.nlm.nih.gov/4015062

2022. A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. The Journal of Biological Chemistry, 298(8).
DOI: 10.1016/j.jbc.2022.102228
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356275

2021. A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome. Cell Reports, 35(4).
DOI: 10.1016/j.celrep.2021.109040
URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545458