33641-15-5

Basic information

• Product Name: 5-Hydroxy-1-methylpyrazole
• Synonyms: 5-HYDROXY-1-METHYL-1H-PYRAZOLE, 95%;1-methyl-1H-pyrazol-5-ol;REF DUPL: 5-Hydroxy-1-methyl-1H-pyrazole;1-Methyl-5-hydroxy-1H-pyrazole;1-Methyl-5-hydroxypyrazole;1-Methylpyrazol-5-ol;5-Hydroxy-1-Methyl-5-pyrazole;1-Methyl-1H-pyrazol-3(2H)-one
• CAS NO: 33641-15-5
• Molecular Formula: C₄H₆N₂O
• Molecular Weight: 98.10324
• Product Categories: Heterocyclic Compounds;Aromatics;Heterocycles;Intermediates
• Mol File: 33641-15-5.mol
• Article Data: 13

Chemical Properties

• Melting Point: 110-114 °C
• Boiling Point: 217.662 °C at 760 mmHg
• Flash Point: 85.439 °C
• Appearance: /
• Density: 1.229 g/cm³
• Vapor Pressure: 0.089mmHg at 25°C
• Refractive Index: 1.568
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 9.07±0.23(Predicted)
• CAS DataBase Reference: 5-Hydroxy-1-methylpyrazole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Hydroxy-1-methylpyrazole(33641-15-5)
• EPA Substance Registry System: 5-Hydroxy-1-methylpyrazole(33641-15-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22-37/38-41
• Safety Statements: 26-39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 33641-15-5(Hazardous Substances Data)

Usage

Description

5-Hydroxy-1-methylpyrazole is a pyrazole derivative characterized by the presence of a hydroxyl group and a methyl group attached to the pyrazole ring. It is an organic compound with potential applications in various industries due to its unique chemical properties.

Uses

Used in Agricultural Industry:
5-Hydroxy-1-methylpyrazole is used as an intermediate in the preparation of herbicides for the agricultural industry. Its role in the synthesis of these herbicides contributes to the development of effective weed control solutions, which are essential for maintaining crop health and productivity.

InChI:InChI=1/C4H6N2O/c1-6-4(7)2-3-5-6/h2-3,7H,1H3

Synthetic route

1-methyl-5-hydroxypyrazol-4-carboxylic acid ethyl ester (88398-78-1) → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
Stage #1: 1-methyl-5-hydroxypyrazol-4-carboxylic acid ethyl ester With sodium hydroxide In water at 40℃; for 3h; Stage #2: With hydrogenchloride for 3h; Reflux;	98%
at 120℃; for 6h; Temperature;

methyl 3-methoxyprop-2-enoate (34846-90-7) + methylhydrazine (60-34-4) → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
In methanol at 0℃; for 4.66667h; Heating / reflux;	73%
In water at 10℃; Temperature;	69.6%
In methanol for 8h; Reflux; Inert atmosphere;
In methanol; water for 2h; Cooling with ice;

aqueous monomethylhydrazine + β-isobutoxyacryl chloride (75945-54-9) → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
With hydrogenchloride; triethylamine In tetrahydrofuran

methyl (2E)-3-methoxy-2-propenoate (5788-17-0) + methylhydrazine (60-34-4) → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
In methanol at 90℃; for 12 - 18h;

methyl crotonate (623-43-8, 4358-59-2, 18707-60-3, 130981-57-6) + methylhydrazine (60-34-4) → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
In methanol for 16h; Reflux; Inert atmosphere;

C6H8N2O3 → 1-methyl-5-hydroxypyrazole (33641-15-5)

Conditions	Yield
With sulfuric acid at 65℃; for 8h; Temperature;	18.6 g

1,4-dioxane (123-91-1) + 3-(3-bromo-2-methyl-6-(methylsulfonyl)phenyl)-4,5-dihydroisoxazole (247922-29-8) + 1-methyl-5-hydroxypyrazole (33641-15-5) → topramezone (210631-68-8)

Conditions	Yield
With carbon monoxide; potassium carbonate; triethylamine; triphenylphosphine; palladium(II) chloride In water	100%
With hydrogenchloride; potassium carbonate; triethylamine; bis(triphenylphosphine)palladium(II) dichloride In water

4-methylsulphonyl-2-nitrobenzoyl chloride (110964-80-2) + 1-methyl-5-hydroxypyrazole (33641-15-5) → (1-methyl-5-hydroxypyrazol-4-yl)-(4-methanesulfonyl-2-nitrophenyl)methanone

Conditions	Yield
With triethylamine In 1,4-dioxane at 5 - 40℃; for 2h;	96%

2-methyl-3-ethylsulfinyl-4-methylsulfonylbenzoic acid (1196958-18-5) + 1-methyl-5-hydroxypyrazole (33641-15-5) → [3-(ethylsulfinyl)-2-methyl-4-(methylsulfonyl)phenyl](5-hydroxy-1-methyl-1H-pyrazol-4-yl)methanone (1196958-05-0)

Conditions	Yield
With pyridine; thionyl chloride In ethyl acetate at -25 - 0℃; Inert atmosphere;	91%

2-methyl-3-(methylsulfinyl)-4-(trifluoromethyl)benzoic acid (1070761-73-7) + 1-methyl-5-hydroxypyrazole (33641-15-5) → (5-hydroxy-1-methyl-1H-pyrazol-4-yl)[2-methyl-3-(methyl-sulfinyl)-4-(trifluoromethyl)phenyl]methanone (1070761-52-2)

Conditions	Yield
With pyridine; thionyl chloride In ethyl acetate at -25 - 0℃; Inert atmosphere;	90.7%

p-toluenesulfonyl chloride (98-59-9) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-1H-pyrazol-5-yl tosylate

Conditions	Yield
With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 2h; Green chemistry;	88%

2-chloro-3-fluoro-4-trifluoromethylbenzoyl chloride + 1-methyl-5-hydroxypyrazole (33641-15-5) → (2-chloro-3-fluoro-4-trifluoromethylphenyl)(5-hydroxy-1-methyl-1H-pyrazol-4-yl)methanone

Conditions	Yield
With triethylamine In 1,2-dichloro-ethane at -5 - 20℃;	86.9%

2-methoxy-3-methylsulfinyl-4-trifluoromethylbenzoic acid (1262652-20-9) + 1-methyl-5-hydroxypyrazole (33641-15-5) → (5-hydroxy-1-methyl-1H-pyrazol-4-yl)[2-methoxy-3-(methylsulfinyl)-4-(trifluoromethyl)phenyl]methanone (1262671-11-3)

Conditions	Yield
With thionyl chloride; 3-Methylpyridine In ethyl acetate at -25 - -20℃; Product distribution / selectivity; Inert atmosphere;	86.5%

2,4-dichlorobenzoyl chloride (89-75-8) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-5-(2,4-dichlorobenzoyloxy)-pyrazole (91436-74-7)

Conditions	Yield
With sodium hydroxide In chloroform	86%

3-(3-bromo-2-methyl-6-(methylsulfonyl)phenyl)-4,5-dihydroisoxazole (247922-29-8) + formyl radical (2597-44-6) + 1-methyl-5-hydroxypyrazole (33641-15-5) → topramezone (210631-68-8)

Conditions	Yield
Stage #1: 3-(3-bromo-2-methyl-6-(methylsulfonyl)phenyl)-4,5-dihydroisoxazole With potassium carbonate In 1,4-dioxane Reflux; Stage #2: 1-methyl-5-hydroxypyrazole With triphenylphosphine; sodium iodide In 1,4-dioxane at 60℃; for 0.5h; Stage #3: formyl radical With palladium on activated charcoal In 1,4-dioxane at 120℃; under 11251.1 Torr; for 20h; Reagent/catalyst; Temperature;	84.4%

3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid (223646-24-0) + 1-methyl-5-hydroxypyrazole (33641-15-5) → topramezone (210631-68-8)

Conditions	Yield
Stage #1: 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid With pyridine; thionyl chloride In benzene for 3h; Reflux; Stage #2: 1-methyl-5-hydroxypyrazole With triethylamine In 1,4-dioxane at 20℃; for 3h; Stage #3: With potassium carbonate for 6h; Reflux;	81.46%
Stage #1: 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid With pyridine; thionyl chloride In toluene for 3h; Reflux; Stage #2: 1-methyl-5-hydroxypyrazole With triethylamine In 1,4-dioxane at 20℃; for 3h;	80.5%
Stage #1: 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid With thionyl chloride for 2h; Reflux; Stage #2: With triethylamine In 1,2-dichloro-ethane at 20 - 30℃; for 0.5h; Stage #3: 1-methyl-5-hydroxypyrazole In 1,2-dichloro-ethane for 4h; Reflux;	20.87%

pentafluorobenzenesulonyl chloride (832-53-1) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-1H-pyrazol-5-yl 2,3,4,5,6-pentafluorobenzenesulfonate

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	81%

3-(3-bromo-2-methyl-6-(methylsulfonyl)phenyl)-4,5-dihydroisoxazole (247922-29-8) + carbon monoxide (201230-82-2) + 1-methyl-5-hydroxypyrazole (33641-15-5) → [3-(4,5-dihydro-1,2-oxazol-3-yl)-4-mesyl-o-tolyl](5-hydroxy-1-methylpyrazol-4-yl)methanone

Conditions	Yield
With potassium carbonate; triethylamine; triphenylphosphine; palladium dichloride In 1,4-dioxane at 120℃; under 4125.41 - 4875.49 Torr; for 40h; Autoclave;	81%

C18H16N2O5 + 1-methyl-5-hydroxypyrazole (33641-15-5) → C22H20N4O5

Conditions	Yield
Stage #1: C18H16N2O5 With thionyl chloride In tetrahydrofuran at 20 - 80℃; for 1.5h; Stage #2: 1-methyl-5-hydroxypyrazole With triethylamine In dichloromethane for 0.5h;	80%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 5-chloro-1-methyl-1H-pyrazole-4-carbaldehyde (117007-77-9)

Conditions	Yield
Stage #1: N,N-dimethyl-formamide; 1-methyl-5-hydroxypyrazole With trichlorophosphate at 80℃; for 6.16667h; Stage #2: With sodium hydrogencarbonate In water	77%
With trichlorophosphate In methanol at 0 - 80℃; for 7h; Inert atmosphere;	12.87 g
With trichlorophosphate at 0 - 80℃; for 12h; Inert atmosphere;	16.31 g

3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid (223646-24-0) + 1-methyl-5-hydroxypyrazole (33641-15-5) → [3-(4,5-dihydro-1,2-oxazol-3-yl)-4-mesyl-o-tolyl](5-hydroxy-1-methylpyrazol-4-yl)methanone

Conditions	Yield
Stage #1: 3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-2-methylbenzoic acid With thionyl chloride for 3h; Reflux; Stage #2: 1-methyl-5-hydroxypyrazole With triethylamine In tetrahydrofuran at 20℃; for 3h; Stage #3: With potassium carbonate In tetrahydrofuran for 2h; Reflux;	76.2%

methanesulfonyl chloride (124-63-0) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methylpyrazole-5-yl methanesulfonate

Conditions	Yield
With triethylamine In ethyl acetate at 0 - 20℃; for 0.166667h; Green chemistry;	74%
With triethylamine In tetrahydrofuran at 0℃; for 2h;	7.04 g

trimethoxonium tetrafluoroborate (420-37-1) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1,2-dimethyl-1,2-dihydropyrazol-3-on (3514-11-2)

Conditions	Yield
In nitromethane at 20℃; for 24h;	71%

p-methoxybenzyl chloride (824-94-2) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-(4-Methoxy-benzyl)-2-methyl-1,2-dihydro-pyrazol-3-one + 5-(4-Methoxy-benzyloxy)-1-methyl-1H-pyrazole

Conditions	Yield
In methanol at 20℃; for 24h;	A 70% B 5%

9-methoxy-6-chloroformyl-3a,4-dihydro-3H-chromeno[4,3-c]isoxazoline (293312-46-6) + 1-methyl-5-hydroxypyrazole (33641-15-5) → (5-hydroxy-1-methyl-1H-pyrazol-4-yl)-(9-methoxy-3a,4-dihydro-3H-chromeno[4,3-c]isoxazolin-6-yl)methanone (293312-16-0)

Conditions	Yield
Stage #1: 9-methoxy-6-chloroformyl-3a,4-dihydro-3H-chromeno[4,3-c]isoxazoline; 1-methyl-5-hydroxypyrazole With trimethylamine In acetonitrile at 0 - 20℃; Stage #2: With potassium carbonate In 1,4-dioxane for 7h; Heating / reflux;	68%

1-methyl-5-hydroxypyrazole (33641-15-5) + benzyl alcohol (100-51-6) → 5-(benzyloxy)-1-methyl-1H-pyrazole

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at -60 - -30℃; for 19h;	66%

3-(2-fluoro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-1H-pyrazol-5-yl 3-(2-fluoro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate

Conditions	Yield
Stage #1: 3-(2-fluoro-4-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 1-methyl-5-hydroxypyrazole With dmap In dichloromethane at 20℃;	65%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 2-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1,2-dihydro-3H-pyrazol-3-one

Conditions	Yield
Stage #1: 1-methyl-5-hydroxypyrazole With potassium carbonate In acetonitrile at 20℃; for 0.5h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In acetonitrile at 20℃; for 14h;	63%
With potassium carbonate In acetonitrile at 20℃; for 16h;	10 g

2-chloro-6-methyl-isonicotinic acid methyl ester (3998-90-1) + 1-methyl-5-hydroxypyrazole (33641-15-5) → methyl 2-(5-hydroxy-1-methyl-1H-pyrazol-4-yl)-6-methylisonicotinate hydrochloride

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate at 130℃; for 16h; Inert atmosphere;	61%

3-(4-chloro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-1H-pyrazol-5-yl 3-(4-chloro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate

Conditions	Yield
Stage #1: 3-(4-chloro-2-methylphenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 1-methyl-5-hydroxypyrazole With dmap In dichloromethane at 20℃;	60%

6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid + 1-methyl-5-hydroxypyrazole (33641-15-5) → C16H12Cl2FN5O3

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine In dichloromethane at 25℃; for 4h;	59%

2-chloro-4-methoxy-3-(1-oxothianylideneamino)benzoic acid (1207343-99-4) + 2-hydroxy-2-methylpropanenitrile (75-86-5) + 1-methyl-5-hydroxypyrazole (33641-15-5) → 2-chloro-1-[(5-hydroxy-1-methylpyrazole-4-yl)carbonyl]-4-methoxy-3-(1-oxothianylideneamino)benzene (1207341-28-3)

Conditions	Yield
Stage #1: 2-chloro-4-methoxy-3-(1-oxothianylideneamino)benzoic acid With 1,1'-carbonyldiimidazole In chloroform at 20℃; for 1h; Stage #2: 1-methyl-5-hydroxypyrazole With triethylamine In chloroform for 1h; Reflux; Stage #3: 2-hydroxy-2-methylpropanenitrile With triethylamine In acetonitrile at 20℃;	55%

3-(4-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid + 1-methyl-5-hydroxypyrazole (33641-15-5) → 1-methyl-1H-pyrazol-5-yl 3-(4-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate

Conditions	Yield
Stage #1: 3-(4-chlorophenyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 1h; Stage #2: 1-methyl-5-hydroxypyrazole With dmap In dichloromethane at 20℃;	53%

Upstream product

• 34846-90-7 methyl 3-methoxyprop-2-enoate 
• 60-34-4 methylhydrazine 
• 88398-78-1 1-methyl-5-hydroxypyrazol-4-carboxylic acid ethyl ester 
• 5788-17-0 methyl (2E)-3-methoxy-2-propenoate 
• 75945-54-9 β-isobutoxyacryl chloride 
• 623-43-8 methyl crotonate 

Downstream Products

• 210631-68-8 topramezone 
• 117007-77-9 5-chloro-1-methyl-1H-pyrazole-4-carbaldehyde 
• 1031359-49-5 3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)benzoic acid 1-methyl-1H-pyrazol-5-yl ester 
• 1159185-84-8 4-(3-(5-chloro-6-(1-methyl-1H-pyrazol-5-yloxy)pyridin-3-ylthio)phenyl)-tetrahydro-2H-pyran-4-carboxamide 
• 1211505-84-8 5-bromo-1-methyl-1H-pyrazole-4-carbaldehyde 

Relevant articles and documents

Synthesis method of 1-methyl-5-hydroxy pyrazole

The invention relates to a synthesis method of 1-methyl-5-hydroxy pyrazole, which comprises the following steps of dropwisely adding tetrahydropyrrole into diethyl ethoxymethylene malonate at room temperature, and reacting at 15-80 DEG C for 2-6 hours to obtain a reaction solution A containing a compound represented by a formula (II), dropwise adding a methylhydrazine aqueous solution into the reaction solution A, and reacting at 15-80 DEG C for 2-6 hours to obtain a reaction solution B containing a compound shown as a formula (III), dropwise adding an acidic solution into the reaction solution B, and heating and refluxing for 4-8 hours at 90-120 DEG C after dropwise adding to obtain a reaction solution C containing a compound shown as a formula (IV), and carrying out post-treatment on thereaction solution C to obtain the target compound 1-methyl-5-hydroxy pyrazole. The synthesis method has the advantages of higher activity, higher reaction rate, better selectivity, higher total yield, cheap and accessible raw materials and simple post-treatment, and can obtain the solid 1-methyl-5-hydroxy pyrazole with higher purity.

Method for preparing 1-methyl-5-hydroxypyrazole by using microchannel reactor

The invention relates to a method for preparing 1-methyl-5-hydroxypyrazole by using a microchannel reactor, and belongs to the technical field of fine chemical engineering. According to the invention, methyl 3-methoxyacrylate and a methylhydrazine aqueous solution are used as reaction raw materials, and the microchannel reactor is used as reaction equipment to prepare 1-methyl-5-hydroxypyrazole. Compared with a kettle type reaction, the yield and the reaction purity are obviously improved. In addition, no solvent is used in the preparation process, so that few hazardous wastes are generated. The microchannel reactor is used for preparing the 1-methyl-5-hydroxypyrazole, continuous production can be achieved, the operation process is simplified, and the production efficiency and safety are improved.

Pyrazole ketone compound or its salt, preparation method thereof, and use of the herbicide composition (by machine translation)

This application pertains to the field of agricultural chemicals, in particular to a pyrazole ketone compound or its salt, preparation method, herbicidal composition and use. The ketone compounds states the pyrazole shown as formula I: In the formula, R 1 R 2 N representative containing substituted or unsubstituted 1-3 of the aza-3-8-membered nitrogen-containing heterocyclic base; or R 1, R 2 respectively represents hydrogen, C 1-8 alkyl etc.; R 3 representative hydrogen, C 1-4 alkyl, alkenyl, alkynyl, or unsubstituted C 1-4 alkyl substituted C 3-6 cycloalkyl; R 4 represents methyl, ethyl, n-propyl, isopropyl, cyclopropyl; X represents hydrogen, -S (O) n R 6, -R 7, containing substituted or unsubstituted 1-4 of the aza-3-8-membered heterocyclic group, wherein n representative 1, 2, 3, R 6 represents a substituted or unsubstituted alkyl or aryl, R 7 represents a substituted or unsubstituted alkyl, aryl, alkanoyl or sweet-smelling acyl. The present invention provides good efficacy of the pharmaceutical actives, easy to use, low cost, has good commercial value. (by machine translation)