176969-34-9

Basic information

• Product Name: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid
• Synonyms: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid;3-Difluoromethyl-1-methyl-1H-pyrazol-4-carboxylic acid;3-Difluoromethyl-1-methylpyrazole-4-carboxylic acid;1H-Pyrazole-4-carboxylicacid, 3-(difluoroMethyl)-1-Methyl-;3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxyl
• CAS NO: 176969-34-9
• Molecular Formula: C₆H₆F₂N₂O₂
• Molecular Weight: 176.121
• Product Categories: Building Blocks;Pyrazole
• Mol File: 176969-34-9.mol

Chemical Properties

• Boiling Point: 315.9 °C at 760 mmHg
• Flash Point: 144.851 °C
• Appearance: /
• Density: 1.52
• Vapor Pressure: 0.000179mmHg at 25°C
• Refractive Index: 1.533
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Sparingly)
• PKA: 3.12±0.36(Predicted)
• CAS DataBase Reference: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid(176969-34-9)
• EPA Substance Registry System: 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid(176969-34-9)

Safety Data

• Hazardous Substances Data: 176969-34-9(Hazardous Substances Data)

Usage

Uses

Used in Pesticide Industry:
3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is used as an active ingredient for the preparation of pesticides. Its chemical structure suggests that it may possess properties effective in controlling pests, particularly in agricultural settings. The difluoromethyl group might enhance its pesticidal activity by potentially increasing its lipophilicity and bioavailability to target pests, while the methyl group could influence its stability and metabolic profile in the environment.

InChI:InChI=1/C6H6F2N2O2/c1-10-2-3(6(11)12)4(9-10)5(7)8/h2,5H,1H3,(H,11,12)

Synthetic route

1-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)ethan-1-one → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With manganese(II) acetate dihydrate; acetic acid at 100℃; for 18h; Reagent/catalyst;	100%
With sodium hypochlorite; sodium hydroxide In water at 70℃; for 2h; Temperature; Reagent/catalyst;	98%
With sodium hypochlorite In water at 0℃; for 0.166667h; Temperature; Time;	98%

ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate (141573-95-7) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium hydroxide In toluene at 65℃; for 0.75h;	98%
With sodium hydroxide In ethanol; water at 50 - 80℃; for 3h;	95%
With water; sodium hydroxide	95%

hexylene glycol bis((3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)carboxylate) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 60℃; for 4h;	96.3%

3‐difluoromethyl‐1‐methylpyrazole-4-carbonyl chloride (141573-96-8) + C12H13Cl2NO (1263184-89-9) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + benzovindiflupyr

Conditions	Yield
Stage #1: 3‐difluoromethyl‐1‐methylpyrazole-4-carbonyl chloride; C12H13Cl2NO With triethylamine In 1,4-dioxane at 25 - 82℃; for 3h; Stage #2: With sodium hydroxide In tert-butyl methyl ether; water for 0.5h; Stage #3: With hydrogenchloride In tert-butyl methyl ether; water	A 96% B 92%

3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonitrile (1049772-84-0) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium hydroxide In water at 90 - 100℃;	95%
Stage #1: 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonitrile With water; sodium hydroxide at 95℃; for 4h; Stage #2: With hydrogenchloride; water at 20℃; Cooling with ice;	92%
With water; sodium hydroxide In methanol for 2h; Solvent; Reflux; Further stages;	92.1%
With tetra(n-butyl)ammonium hydrogensulfate; sodium hydroxide In water; toluene at 70℃; for 8h;

hexyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With water; sodium hydroxide at 60℃; for 2h;	95%

methyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With manganese(II) nitrate; oxygen; acetic acid; ferric nitrate at 80℃; for 20h;	95%

3-(difluoromethyl)-1-methyl-4-(1,3-dioxolan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(1,3-dioxolan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With dihydrogen peroxide In water at 10 - 100℃; for 5h; Reagent/catalyst;	93.2%

3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With dihydrogen peroxide In water at 10 - 100℃; for 5h;	92.3%

ethylene glycol bis((3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)carboxylate) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With water; sodium hydroxide In methanol at 60℃; for 4h; Reagent/catalyst;	92%

3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxepan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxepan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With dihydrogen peroxide In water at 10 - 100℃; for 5h;	92%

3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxolan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxolan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With sodium hypochlorite In water at 10 - 100℃; for 5h;	91.8%

3-(difluoromethyl)-4-(1,3-dioxan-2-yl)-1-methyl-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-4-(1,3-dioxan-2-yl)-1-methyl-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With dihydrogen peroxide In water at 10 - 100℃; for 5h; Reagent/catalyst;	91.6%

3-(difluoromethyl)-1-methyl-4-(1,3-dioxepan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(1,3-dioxepan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With dihydrogen peroxide In water at 10 - 100℃; for 5h; Reagent/catalyst;	91.5%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde (1094484-55-5) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium hypochlorite at 10 - 100℃; for 5h;	91.3%
Stage #1: 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbaldehyde With sodium hydroxide; dihydrogen peroxide In water at 40 - 45℃; for 1.5h; Stage #2: With hydrogenchloride In water pH=2.5; Product distribution / selectivity;	69 %Chromat.
With copper(II) oxide; sodium hydroxide In water at 25 - 30℃; for 24h;	32 g

3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxetan-2-yl)-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-4-(2-methyl-1,3-dioxetan-2-yl)-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With sodium hypochlorite In water at 10 - 100℃; for 5h; Reagent/catalyst;	91.3%

2,2-dichloro-1-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)ethanone → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium hypochlorite; water In chloroform at 24℃; for 4h; Reagent/catalyst; Inert atmosphere;	91%
With sodium hypochlorite; sodium hydroxide In water at 22 - 70℃; for 2h;

3-(difluoromethyl)-4-(1,3-dioxetan-2-yl)-1-methyl-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-4-(1,3-dioxetan-2-yl)-1-methyl-1H-pyrazole With hydrogenchloride In water at 50 - 60℃; for 5h; Stage #2: With sodium hypochlorite In water at 10 - 100℃; for 5h; Reagent/catalyst;	91%

methyl-3-(dichloromethyl)-1-methyl-1H-pyrazole-4-carboxylate → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + 5-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (1204298-65-6)

Conditions	Yield
With 1,3-dimethyl-2-imidazolidinone; hydrogen fluoride; triethylamine at 125 - 155℃; Reagent/catalyst; Temperature; Concentration; Autoclave;	A 90.1% B n/a

3-(difluoromethyl)-4-(furan-2-yl)-1-methyl-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium periodate; rhodium(III) chloride hydrate In tetrachloromethane; water; acetonitrile at 20℃; for 0.75h;	90%

3-bromo-1-methyl-1H-pyrazole-4-carboxylic acid + difluoromethylboronic acid → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane; water at 65 - 75℃; for 1.5h; Solvent; Reagent/catalyst; Inert atmosphere;	89.2%

(E/Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: methylhydrazine With benzaldehyde In water; toluene at 25 - 60℃; for 6.16667h; Inert atmosphere; Stage #2: (E/Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate In water; toluene at 20 - 30℃; for 19h; Product distribution / selectivity;	86.1%

4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole (1089212-38-3) + carbon dioxide (124-38-9) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole With TurboGrignard In 2-methyltetrahydrofuran at -5℃; for 2h; Inert atmosphere; Heating; Stage #2: carbon dioxide In 2-methyltetrahydrofuran at -25 - 0℃; for 5h; Reagent/catalyst; Solvent; Inert atmosphere;	84.6%

ethyl 4,4-difluoro-3-oxobutyrate (352-24-9) + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: ethyl 4,4-difluoro-3-oxobutyrate With calcium acetate; orthoformic acid triethyl ester at 100 - 110℃; for 2h; Stage #2: methylhydrazine With sodium hydroxide In 5,5-dimethyl-1,3-cyclohexadiene; water at 10 - 20℃; for 0.5h;	83.3%

carbon dioxide (124-38-9) + 3-(difluoromethyl)-4-iodo-1-methyl-1H-pyrazole → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-4-iodo-1-methyl-1H-pyrazole With isopropylmagnesium chloride In tetrahydrofuran at -5℃; for 2h; Inert atmosphere; Heating; Stage #2: carbon dioxide With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at -25 - 0℃; for 5h; Inert atmosphere;	83.2%

potassium 2-difluoroacetyl-3-(diethylamino)acrylate + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With potassium iodide In water at -30 - -20℃; for 2h; Inert atmosphere;	79.6%

sodium 2-difluoroacetyl-3-(dimethylamino)acrylate + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium iodide In water at -30 - 20℃; for 2h; Inert atmosphere;	78.3%

sodium 2-difluoroacetyl-3-(diethylamino)acrylate + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium iodide at -30 - -25℃; for 2h; Inert atmosphere;	77.1%

potassium 2-difluoroacetyl-3-(dimethylamino)acrylate → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With methylhydrazine; potassium iodide In water at -30 - -20℃; for 2h; Inert atmosphere;	75.9%

sodium 2-difluoroacetyl-3-(2,2,6,6-tetramethylpiperidin-1yl)acrylate + methylhydrazine (60-34-4) → 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9)

Conditions	Yield
With sodium iodide at -30 - -20℃; for 2h; Inert atmosphere;	75.8%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) → 3‐difluoromethyl‐1‐methylpyrazole-4-carbonyl chloride (141573-96-8)

Conditions	Yield
With thionyl chloride In chlorobenzene at 110℃; for 3h;	98%
With thionyl chloride In toluene at 90℃;	92.1%
With thionyl chloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 5h; Reflux;	90%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) → 1-methyl-3-(difluoromethyl)-1H-pyrazole-4-amide (925689-10-7)

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 0.5h; Stage #2: With ammonium hydroxide In dichloromethane Cooling with ice;	98%
Multi-step reaction with 2 steps 1: thionyl chloride / 4 h / Reflux 2: ammonium hydroxide / dichloromethane / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: thionyl chloride / 4 h / Reflux 2: ammonium hydroxide / tetrahydrofuran View Scheme
Multi-step reaction with 2 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0.5 h / 20 °C 2: ammonium hydroxide / dichloromethane / 0 °C View Scheme
Stage #1: 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With ammonium hydroxide at 0 - 20℃;

methanol (67-56-1) + 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) → methyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate

Conditions	Yield
With sulfuric acid at 75℃; for 8h;	97.2%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + tert-butyl alcohol (75-65-0) → tert-butyl (3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)carbamate

Conditions	Yield
With diphenylphosphoranyl azide; N-ethyl-N,N-diisopropylamine at 20 - 90℃; for 4.16667h; Inert atmosphere;	94%
With diphenyl phosphoryl azide; N-ethyl-N,N-diisopropylamine at 20 - 90℃; for 4.16667h; Curtius Rearrangement; Inert atmosphere;	94%
With diphenyl phosphoryl azide; N-ethyl-N,N-diisopropylamine at 20 - 90℃; for 4.5h; Inert atmosphere;	91%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + 5-amino-9-syn-isopropyl-benzonorbornene → C20H23F2N3O

Conditions	Yield
With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In dichloromethane at 20℃; for 21h;	92.6%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + C14H19N → C20H23F2N3O

Conditions	Yield
With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In dichloromethane at 20℃; for 3h;	91.7%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) → tert-butyl (3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)carbamate

Conditions	Yield
With diphenylphosphoranyl azide; N-ethyl-N,N-diisopropylamine In tert-butyl alcohol at 20 - 90℃; for 4.5h; Inert atmosphere;	91%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + N,O-dimethylhydroxylamine*hydrochloride (6638-79-5) → N-methoxy,N-methyl-1-methyl-3-(difluoromethyl)-1H-pyrazole-4-carboxylic amide

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 0.5h; Stage #2: N,O-dimethylhydroxylamine*hydrochloride In dichloromethane at 20℃;	91%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	91%

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) → 3-(difluoromethyl)-4-iodo-1-methyl-1H-pyrazole

Conditions	Yield
With potassium iodate; sulfuric acid; iodine; acetic acid In sulfolane at 45 - 60℃; for 1.33h;	90%
Multi-step reaction with 3 steps 1.1: diphenylphosphoranyl azide; N-ethyl-N,N-diisopropylamine / 4.17 h / 20 - 90 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 2.5 h / 20 °C 3.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 °C 3.2: 0.5 h View Scheme
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine; diphenyl phosphoryl azide / 4.17 h / 20 - 90 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 2.5 h / 20 °C 3.1: hydrogenchloride; sodium nitrite / water / 1 h / 0 °C 3.2: 0.5 h / 20 °C View Scheme

3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid (176969-34-9) + C12H17BrN2O2S → N-(2-bromophenyl)-2-(1-methyl-3-difluoromethyl-1H-pyrazole-4-carboxylamino)-cyclohexylsulfonamide

Conditions	Yield
Stage #1: 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 2h; Inert atmosphere; Stage #2: C12H17BrN2O2S In dichloromethane at 0℃; for 3h; Inert atmosphere;	90%

Upstream product

• 1334398-13-8 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid, sodium salt 
• 1089212-37-2 3-(difluoromethyl)-1-methyl-1H-pyrazole 
• 109-61-5 propoxycarbonyl chloride 
• 592-34-7 carbonochloridic acid, butyl ester 
• 543-27-1 isobutyl chloroformate 
• 108-23-6 isopropyl chloroformate 
• 1186318-47-7 ethyl 4,4-difluoro-2-[1-{N-methyl-N'-[1-phenylmethylidene]hydrazino}-methylidene]-3-oxobutyrate 
• 60-34-4 methylhydrazine 
• 176969-33-8 ethyl α-ethoxymethylene-4,4-difluoro-3-oxobutyrate 

Downstream Products

• 141573-96-8 3‐difluoromethyl‐1‐methylpyrazole-4-carbonyl chloride 
• 1801762-09-3 3-(difluoromethyl)-1-methyl-4-amino-1H-pyrazole 

Relevant articles and documents

Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy

The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound W2 showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound W2 encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in W2 could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.

PRODUCING METHOD FOR 3-DIFLUOROMETHYLPYRAZOLE COMPOUND, PRODUCING METHOD FOR 3-DIFLUOROMETHYLPYRAZOLE-4-CARBOXYLIC ACID COMPOUND, AND PYRAZOLIDINE COMPOUND

Provided are producing methods for a 3-difluoromethylpyrazole compound and a 3-difluoromethylpyrazole-4-carboxylic acid compound, which include, in a reaction solvent containing a specific solvent, subjecting a difluoroacetyl group-containing compound, a hydrazine compound, and formaldehyde to a cyclocondensation reaction, and subsequently oxidizing the obtained pyrazole compound precursor, and a pyrazolidine compound represented by a specific formula in these producing methods.

Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the technical field of organic synthesis. The preparation method comprises thefollowing steps: by taking 2, 2-difluoroacetyl halide as a raw material, performing addition with alpha, beta-unsaturated ester, performing alkaline hydrolysis to obtain alpha-difluoroacetyl intermediate carboxylic acid, condensing and cyclizing the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid with a methylhydrazine aqueous solution in the presence of a catalyst to obtain a 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid crude product, and recrystallizing to obtain a pure product of the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The method has the advantages of simple operation, easily available raw materials, high reaction yield, reduction of isomers through a plurality of ways in the reaction process, and convenience in product purification.

Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the technical field of organic synthesis. The preparation method comprises thefollowing steps: reacting N-methyl-3-aminopyrazole as a raw material with bromine/iodine to replace pyrazole at site 4, then carrying out diazotizing and coupling with potassium difluoromethyl trifluoroborate to obtain 4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole, then performing Grignard exchange by adopting isopropyl magnesium chloride and the like, and performing reaction with carbon dioxide to obtain 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The method is simple and convenient to operate, the total yield of the three steps is as high as 64%, the product purity can reach 99.5% or above, the situation in which isomers exist in a traditional process is avoided, and the method has potential process amplification prospects.

Preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

The invention discloses a preparation method of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid, and belongs to the field of pesticide organic synthesis. The preparation method comprises thefollowing steps: step 1, enabling 1-methyl-3-(trimethylsilyl) pyrazole to react with halogen to obtain 4-halogen-1-methyl-3-(trimethylsilyl) pyrazole; step 2, after exchange is conducted through a Grignard reagent, enabling the 4-halogen-1-methyl-3-(trimethylsilyl) pyrazole to react with chloroformate to obtain 1-methyl-3-trimethylsilyl-1H-pyrazole-4-carboxylic acid; step 3, then carrying out a heating reaction with bromine, so as to obtain 3-bromo-1-methyl-1H-pyrazole-4-carboxylic acid; and step 4, finally, carrying out heating coupling on the 3-bromo-1-methyl-1H-pyrazole-4-carboxylic acid and difluoromethylboronic acid by adopting a palladium catalyst, and performing recrystallization to obtain the 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid. The invention provides a new synthesis path for the synthesis of the compound, and has a potential industrial method prospect.

Preparation method and application of pyrazole derivative

The invention relates to a preparation method of a pyrazole derivative. The compound shown in the formula I reacts with a silanization reagent shown in a formula II to generate an intermediate productshown in a formula III, the intermediate product shown in the formula III reacts with a halogenated acid derivative shown in a formula IV to generate a halogenated compound shown in a formula V, andthe halogenated compound shown in the formula V reacts under acidic conditions to generate a pyrazole derivative shown in a formula VI. The preparation method of the pyrazole derivative is suitable for industrial production.

Method for synthesizing 3- difluoro methyl -1- methyl -1H- pyrazole -4- carboxylic acid by one-pot method

The invention discloses a method for synthesizing 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid by a one-pot method, wherein the method includes the following steps: in xylene, carrying outa condensation reaction of 4,4-difluoroethylacetoacetate and triethyl orthoformate under heating and catalysis of metal carboxylate, cooling, then dropwise adding a methylhydrazine aqueous solution, then heating up, carrying out a ring closing reaction, carrying out saponification and acidification of the obtained ring-closed reaction liquid, and thus obtaining the 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid. The method is reasonable in design, high in yield, simple in process operation, low in cost, and suitable for industrialized production.

METHOD FOR PRODUCING HALOGEN-CONTAINING PYRAZOLE CARBOXYLIC ACID AND INTERMEDIATE THEREOF

The invention provides a method capable of more simply and efficiently producing halogen-containing pyrazolecarboxylic acids and intermediates thereof, which are useful as pharmaceutical or agrochemical intermediates, in a manner suitable for industrial production. In particular, the invention provides a method of producing a compound represented by the formula (b), which comprises reacting a compound represented by the formula (a) with a halogenating agent selected from the group consisting of a compound represented by X2 (formula (1)), a compound represented by SOX2 (formula (2)), and a compound represented by SO2X2 (formula (3)) to obtain the compound represented by the formula (b): formula (1) X2 formula (2) SOX2 formula (3) SO2X2 wherein each symbol is as described in the description.

PRODUCTION METHOD FOR HALOGENATED PYRAZOLECARBOXYLIC ACID

The invention provides a method capable of more simply and efficiently producing halogen-containing pyrazolecarboxylic acids useful as pharmaceutical or agrochemical intermediates, in a manner suitable for industrial production. In particular, the invention provides a method of producing a compound represented by the formula (b), which comprises reacting a compound represented by the formula (a) with oxygen in the presence of a compound containing a transition metal atom to obtain the compound represented by the formula (b): wherein each symbol is as described in the description.

Synthesis and biological activity of acyl thiourea containing difluoromethyl pyrazole motif

A series of new acyl thiourea derivatives containing difluoromethyl pyrazole moiety were designed and synthesized. Their structures were confirmed by 1H NMR, 31C NMR, MS and HRMS. The bioassay results showed that some of title compounds exhibited good in vivo fungicidal activity against Botrytis cinerea and Fusarium oxysporum and good antibacterial activity against Pseudomonas syringae pv. Lachrymans at 50 mg/L respectively.