25629-50-9

Basic information

• Product Name: 3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride
• Synonyms: 3-(2-chlorophenyl)-5-methyl-4-isoxazolecarbonylchlorid;4-Isoxazolecarbonyl chloride, 3-(2-chlorophenyl)-5-methyl-;4-Isoxazolecarbonyl chloride, 3-(o-chlorophenyl)-5-methyl- (8ci);Einecs 247-137-4;Nsc 81237;[3-(2-chlorophenyl)-5-Methyl-1,2-oxazol-4-yl](forMyl)chloranuide;4-Isoxazolecarbonyl chloride, 3-(o-chlorophenyl)-5-methyl-;3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chlorid
• CAS NO: 25629-50-9
• Molecular Formula: C₁₁H₇Cl₂NO₂
• Molecular Weight: 256.08
• EINECS: 247-137-4
• Product Categories: Aromatics;Heterocycles;Oxazole&Isoxazole
• Mol File: 25629-50-9.mol
• Article Data: 9

Chemical Properties

• Melting Point: 41-42°C
• Boiling Point: 381.7 °C at 760 mmHg
• Flash Point: 184.6 °C
• Appearance: Cream solid
• Density: 1.381 g/cm³
• Vapor Pressure: 4.99E-06mmHg at 25°C
• Refractive Index: 1.574
• PKA: -5.80±0.50(Predicted)
• Water Solubility: 128.2mg/L at 25℃
• Sensitive: Moisture Sensitive
• BRN: 791931
• CAS DataBase Reference: 3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride(25629-50-9)
• EPA Substance Registry System: 3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride(25629-50-9)

Safety Data

• Statements: 34
• Safety Statements: 26-36/37/39-45-36/45
• RIDADR: 3261
• TSCA: Yes
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 25629-50-9(Hazardous Substances Data)

Usage

Chemical Properties

3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride is Cream solid

Uses

3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl chloride is used for preparing isoxazolyl penicillin derivatives.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C11H7Cl2NO2/c1-6-9(11(13)15)10(14-16-6)7-4-2-3-5-8(7)12/h2-5H,1H3

Synthetic route

3-(2-chlorophenyl)-5-methyl-4-isoxazolecarboxylic acid (23598-72-3) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
With phosphorus pentachloride at 45℃; for 1h;	93%
With thionyl chloride
With thionyl chloride; sodium hydrogencarbonate In ice-water; dichloromethane; water

2-chloro benzaldehyde oxime (3717-28-0) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: Cl2 2: (i) Na, MeOH, (ii) /BRN= 2502600/ 3: aq. KOH / ethanol 4: SOCl2 View Scheme
Multi-step reaction with 4 steps 1.1: chlorine / methanol / 0 - 5 °C 2.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 2.2: 2 h / 0 - 20 °C / pH 9 3.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux 4.1: phosphorus pentachloride / 1 h / 45 °C View Scheme
Multi-step reaction with 4 steps 1: N-chloro-succinimide / N,N-dimethyl-formamide / 20 °C 2: triethylamine / dichloromethane / 20 °C 3: potassium hydroxide / water; ethanol / 20 °C 4: thionyl chloride / Reflux View Scheme

methyl 3-(2'-chlorophenyl)-5-methylisoxazole-4-carboxylate (4357-94-2) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. KOH / ethanol 2: SOCl2 View Scheme
Multi-step reaction with 2 steps 1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux 2: phosphorus pentachloride / 1 h / 45 °C View Scheme
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 3 h 2: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 40 °C View Scheme

2-chloro-N-hydroxybenzimidoyl chloride (29568-74-9) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: (i) Na, MeOH, (ii) /BRN= 2502600/ 2: aq. KOH / ethanol 3: SOCl2 View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 1.2: 2 h / 0 - 20 °C / pH 9 2.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux 3.1: phosphorus pentachloride / 1 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 20 °C 2: potassium hydroxide / water; ethanol / 20 °C 3: thionyl chloride / Reflux View Scheme

2-chloro-benzaldehyde (89-98-5) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: hydroxylamine sulfate / methanol / 0.5 h 1.2: 0.5 h / pH 8 - 9 / Reflux 2.1: chlorine / methanol / 0 - 5 °C 3.1: sodium hydroxide / methanol / 0.5 h / 0 - 5 °C / pH 10 3.2: 2 h / 0 - 20 °C / pH 9 4.1: water; sodium hydroxide / methanol / 1 h / pH 11 - 13 / Reflux 5.1: phosphorus pentachloride / 1 h / 45 °C View Scheme
Multi-step reaction with 2 steps 1.1: hydroxylamine sulfate / methanol / 1 h / 20 - 40 °C 1.2: 24 h / 0 - 20 °C / pH ~ 9.5 / Inert atmosphere 1.3: pH ~ 7 - 7.5 2.1: phosphorus pentachloride / toluene View Scheme
Multi-step reaction with 5 steps 1: hydroxylamine hydrochloride; sodium carbonate / 20 °C 2: N-chloro-succinimide / N,N-dimethyl-formamide / 20 °C 3: triethylamine / dichloromethane / 20 °C 4: potassium hydroxide / water; ethanol / 20 °C 5: thionyl chloride / Reflux View Scheme

ethyl 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxylate (83817-50-9) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / water; ethanol / 20 °C 2: thionyl chloride / Reflux View Scheme

3-amino-naphthalene-1,8-dicarboxylic acid-anhydride (23204-38-8) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C23H13ClN2O5 (1420467-57-7)

Conditions	Yield
With pyridine In diethyl ether at 60 - 80℃;	98%

anthranilic acid (118-92-3) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 2-(3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido)benzoic acid

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 2h;	94%

3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamide (53013-51-7)

Conditions	Yield
With ammonia at 100℃; for 1h; Sealed tube;	93%
With ammonium hydroxide In acetone

para-fluorobenzylamine (140-75-0) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C18H14ClFN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	93%

2-octyn-1-ol (20739-58-6) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid oct-2-ynyl ester

Conditions	Yield
With zinc In benzene for 0.133333h; Esterification;	92%

3-bromo-N-hydroxybenzimidamide (173406-70-7) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → (Z)-3-bromo-N'-((3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl)oxy)benzimidamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	92%

4-chloro-aniline (106-47-8) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C17H12Cl2N2O2 (153947-71-8)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	92%

p-toluidine (106-49-0) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C18H15ClN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	92%

3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) + (Z)-N′-hydroxy-3-methoxybenzimidamide (934367-07-4, 73647-50-4) → (Z)-N′-((3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl)oxy)-3-methoxybenzimidamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 20h;	91%

pentan-1-ol (71-41-0) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid pentyl ester

Conditions	Yield
With zinc In benzene for 0.1h; Esterification;	90%

(+)-D-glucosamine hydrochloride (1078691-95-8) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → N-(3-(2-chlorophenyl)-5-methyl-4-isoxazole)formylamino-2-deoxyglucose

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at -5℃; for 4h;	90%

4-fluoroaniline (371-40-4) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C17H12ClFN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	90%

4-(trifluoromethoxy)aniline (461-82-5) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C18H12ClF3N2O3

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	90%

1-amino-naphthalene (134-32-7) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C21H15ClN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	90%

3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) + benzyl alcohol (100-51-6) → 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid benzyl ester

Conditions	Yield
With zinc In benzene for 0.166667h; Esterification;	89%

isopropyl alcohol (67-63-0) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid isopropyl ester

Conditions	Yield
With zinc In benzene for 0.15h; Esterification;	88%

dimethylenecyclourethane (497-25-6) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C14H11ClN2O4

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃;	87.3%

thiosemicarbazide (79-19-6) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C12H11ClN4O2S

Conditions	Yield
With sodium hydrogencarbonate In acetone Cooling with ice;	87%

piperidine (110-89-4) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C16H17ClN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	87%

trimethylsilylazide (4648-54-8) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 1-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)-1,4-dihydro-5H-tetrazol-5-one

Conditions	Yield
at 20 - 100℃; Sealed tube;	86%

3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 1-(3-(2-chlorophenyl)-5-methylisoxazol-4-yl)-1,4-dihydro-5H-tetrazol-5-one

Conditions	Yield
With trimethylsilylazide at 100℃; Sealed tube;	86%

3-chloro-4-fluorophenylamine (367-21-5) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C17H11Cl2FN2O2

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	86%

3-methyl-2-buten-1-ol (556-82-1) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid 3-methyl-but-2-enyl ester

Conditions	Yield
With zinc In benzene for 0.133333h; Esterification;	85%

morpholine (110-91-8) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C15H15ClN2O3

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	84%

(Z)-N'-hydroxy-4-(1,2,3-thiadiazol-4-yl)benzimidamide + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → (Z)-N'-((3-(2-chlorophenyl)-5-methyl isoxazole-4-carbonyl)oxy)-4-(1,2,3-thiadiazol-4-yl)benzimidamide

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 1.5h;	83%

(Z)-2-(benzo[d]thiazol-2-yl)-N′-hydroxyacetimidamide + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → (Z)-2-(benzo[d]thiazol-2-yl)-N′-((3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl)oxy)acetimidamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 20h;	82%

2-thiazolylamine (96-50-4) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C14H10ClN3O2S

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	82%

3-nitro-aniline (99-09-2) + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → C17H12ClN3O4

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice;	81%

(Z)-4-((6-chloropyridin-3-yl)methoxy)-N'-hydroxybenzimidamide + 3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl chloride (25629-50-9) → (Z)-N'-((3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl)oxy)-4-((6-chloropyridin-3-yl)methoxy)benzimidamide

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 15h;	80%

Upstream product

• 83817-50-9 ethyl 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxylate 
• 89-98-5 2-chloro-benzaldehyde 
• 29568-74-9 2-chloro-N-hydroxybenzimidoyl chloride 
• 4357-94-2 methyl 3-(2'-chlorophenyl)-5-methylisoxazole-4-carboxylate 
• 3717-28-0 2-chloro benzaldehyde oxime 
• 23598-72-3 3-(2-chlorophenyl)-5-methyl-4-isoxazolecarboxylic acid 

Downstream Products

• 30154-75-7 O-{6β-[3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carbonylamino]-penicillanoyl}-N-benzylidene-hydroxylamine 
• 53013-51-7 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamide 
• 497258-65-8 (+)-pinanediol (1R)-1-{[3-(2-chlorophenyl)-5-methylisoxazole-4-carbonyl]amino}-1-[3-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)phenyl]methylboronate 
• 869807-31-8 3-(2-chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluoro-phenyl)-cyclohexyl]-amide 
• 1391026-02-0 prop-2-ynyl 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxylate 

Relevant articles and documents

Design, synthesis, and insecticidal activity of novel isoxazole derivatives containing bisamide moiety

In this study, a total of 31 novel isoxazole derivatives containing bisamide moiety were synthesized and evaluated for their insecticidal activity against Plutella xylostella (P. xylostella). Bioassays indicated that some of the target compounds exhibited good insecticidal activity against P. xylostella. In particular, compound E26 revealed excellent insecticidal activity against P. xylostella, with a 50% lethal concentration (LC50) value of 4.6 μg/mL, which was even better than those of chlorpyrifos (7.7 μg/mL), beta-cypermethrin (12.8 μg/mL), and azadirachtin (10.2 μg/mL). These results indicated that isoxazole derivatives containing bisamide moiety could be developed as novel and promising insecticides. To the best of our knowledge, it is the first report on the insecticidal activity of this series of novel isoxazole derivatives containing bisamide moiety.

Design, synthesis, and bioevaluation of substituted phenyl isoxazole analogues as herbicide safeners

Herbicide safeners enhance herbicide detoxification in crops without affecting target weed sensitivity. To enhance crop tolerance to the toxicity-related stress caused by the herbicide acetochlor (ACT), a new class of substituted phenyl isoxazole derivatives was designed by an intermediate derivatization method as herbicide safeners. Microwave-assisted synthesis was used to prepare the phenyl isoxazole analogues, and all of the structures were confirmed via IR, 1H NMR, 13C NMR, and HRMS. Compound I-1 was further characterized by X-ray diffraction analysis. Bioassay results showed that most of the obtained compounds provided varying degrees of safening against ACT-induced injury by increasing the corn growth recovery, glutathione content, and glutathione S-transferase activity. In particular, compound I-20 showed excellent safener activity against ACT toxicity, comparable to that of the commercial safener benoxacor. Gaussian calculations have been performed and the results indicated that the nucleophilic ability of compound I-20 is higher than that of benoxacor, thus the activity is higher than that of benoxacor. These findings demonstrate that phenyl isoxazole derivatives possess great potential for protective management in cornfields.

Synthesis of 1,2,3-triazole substituted isoxazoles via copper (I) catalyzed cycloaddition

The synthesis of a series of 3,5-disubstituted isoxazole-4-carboxylic esters containing N-substituted 1,2,3-triazoles (V) starting from various benzaldehydes (I) is reported. Benzaldehydes undergo oximation with hydroxylamine hydrosulfate. Later, chlorination followed by condensation with methylacetoacetate and the hydrolysis of the resulting ester afforded respective carboxylic acid (II), which on chlorination with PCl5 gave the corresponding acid chlorides (III). The coraboxylic acid chlorides (III) on propargylation gave propargylic esters (IV) and these on click reaction gave the title compounds (V).