77087-34-4

Basic information

• Product Name: (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one
• Synonyms: (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one;(4S)-Hydroxy-3-methyl-2-(2-propynyl)-2-cyclopentene-1-one;S-2-methyl-3-(2-propynyl)-4-oxo-cyclopent-2-enol;(4S)-4-hydroxy-3-methyl-2-propargyl-cyclopent-2-en-1-one
• CAS NO: 77087-34-4
• Molecular Formula: C₉H₁₀O₂
• Molecular Weight: 150.17
• Mol File: 77087-34-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 284.6°C at 760 mmHg
• Flash Point: 119.4°C
• Appearance: /
• Density: 1.161g/cm³
• Vapor Pressure: 0.000338mmHg at 25°C
• Refractive Index: 1.544
• PKA: 12.76±0.60(Predicted)
• CAS DataBase Reference: (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one(CAS DataBase Reference)
• NIST Chemistry Reference: (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one(77087-34-4)
• EPA Substance Registry System: (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one(77087-34-4)

Safety Data

• Hazardous Substances Data: 77087-34-4(Hazardous Substances Data)

Usage

General Description

"(4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one" is a chemical compound with the molecular formula C9H10O2. It is a ketone with a cyclopentenone structure, containing a hydroxyl group and a propynyl substituent. (4S)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-en-1-one is commonly referred to as cicutoxin and is found in the roots of the water hemlock plant (Cicuta spp.). Cicutoxin is a highly toxic substance that acts as a convulsant and can cause central nervous system paralysis and ultimately death. It inhibits the function of the GABA receptors in the brain, leading to overexcitation of neurons and the development of seizures. It is important to handle this compound with extreme caution due to its potent toxicity.

InChI:InChI=1/C9H10O2/c1-3-4-7-6(2)8(10)5-9(7)11/h1,8,10H,4-5H2,2H3/t8-/m0/s1

Synthetic route

C9H11BO4 (139107-32-7) → (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With water; calcium carbonate at 85℃; for 4h; Yield given. Yields of byproduct given;

(+/-)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (96189-00-3) → (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With Arthrobacter lipase; water; methanesulfonyl chloride Product distribution; Multistep reaction; methodology for preparation of secondary (S)-alcohol from the corresponding racemic acetate; further acetates;

(S)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (90428-87-8) → (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With water; nitric acid at 80℃;

(S)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (90428-87-8) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With sulfuric acid at 80℃; for 3h; or 2.5percent aq. HNO3;	96 % Chromat.
Multi-step reaction with 3 steps 1: H2O, 2,5percent HNO3 / 80 °C 2: 97 percent Chromat. / fuming HNO3 3: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, 2,5percent HNO3 / 80 °C 2: 97 percent Chromat. 3: H2O, CaCO3 / 4 h / 85 °C View Scheme

(R)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl nitrate (94412-95-0) → (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With water; calcium carbonate at 85℃; for 4h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With water; calcium carbonate at 85℃; for 4h; Yield given. Yields of byproduct given;
With water; calcium carbonate at 85℃; for 4h; Product distribution; different amounts of CaCO3; or mesylate instead of nitrate;

(R)-2-methyl-4-oxo-3-(2-propynyl)-2-cyclopentenyl methanesulfonate (95413-30-2) → (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
With water; calcium carbonate at 85℃; for 4h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With water; calcium carbonate at 85℃; for 4h; Yield given. Yields of byproduct given;

C9H11BO4 (139107-32-7) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: fuming HNO3 3: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: 97 percent Chromat. / fuming HNO3 3: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 3: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: 97 percent Chromat. 3: H2O, CaCO3 / 4 h / 85 °C View Scheme

(R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (77832-42-9) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: fuming HNO3 2: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 2 steps 1: 97 percent Chromat. / fuming HNO3 2: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 2 steps 2: H2O, 2,5percent HNO3 / 80 °C View Scheme

(+/-)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one (96189-00-3) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 46 percent / arthrobacter lipase 2: fuming HNO3 3: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 3 steps 1: 46 percent / arthrobacter lipase 2: 97 percent Chromat. / fuming HNO3 3: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 4 steps 1: 46 percent / arthrobacter lipase 2: H2O, 2,5percent HNO3 / 80 °C 3: 97 percent Chromat. / fuming HNO3 4: H2O, CaCO3 / 4 h / 85 °C View Scheme

(R)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl nitrate (94412-95-0) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 3: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: 97 percent Chromat. 3: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C / different amounts of CaCO3; or mesylate instead of nitrate 2: triethylamine / acetone / 2 h / -15 °C 3: H2O, CaCO3 / 4 h / 85 °C View Scheme

(R)-2-methyl-4-oxo-3-(2-propynyl)-2-cyclopentenyl methanesulfonate (95413-30-2) → (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: fuming HNO3 3: H2O, 2,5percent HNO3 / 80 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: 97 percent Chromat. / fuming HNO3 3: H2O, CaCO3 / 4 h / 85 °C View Scheme
Multi-step reaction with 3 steps 1: H2O, CaCO3 / 4 h / 85 °C 2: 90percent HNO3, acetic anhydride / 1 h / 0 °C 3: H2O, CaCO3 / 4 h / 85 °C / different amounts of CaCO3; or mesylate instead of nitrate View Scheme

(1R)-trans-3-(2-methyl-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride (4489-14-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-3-propargyl-2-methyl-4-oxocyclopent-2-enyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate

Conditions	Yield
With pyridine In toluene at 5 - 15℃; for 3h; Solvent; Temperature;	91.2%

(1R,3R)-trans-chrysanthemic acid (4638-92-0) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-3-propargyl-2-methyl-4-oxocyclopent-2-enyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylate

Conditions	Yield
Stage #1: (1R,3R)-trans-chrysanthemic acid With 1-methyl-1H-imidazole; p-toluenesulfonyl chloride In acetonitrile at 20 - 25℃; for 0.5h; Stage #2: (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one In acetonitrile at 20 - 25℃; for 2h; Further stages.;	91%

1H-imidazole (288-32-4) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) + tert-butyldimethylsilyl chloride (18162-48-6) → (S)-4-tert-butyldimethylsilyloxy-3-methyl-2-(2-propynyl)cyclopent-2-ene-1-one (160600-75-9)

Conditions	Yield
In N-methyl-acetamide	86%

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-4-trimethylsilyloxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one

Conditions	Yield
With chloro-trimethyl-silane; triethylamine In tetrahydrofuran	79.1%

Vinyl bromide (593-60-2) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-(+)-4-hydroxy-3-methyl-2-(pent-4-en-2-ynyl)-2-cyclopenten-1-one

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine In toluene at 20 - 25℃; for 16h; Inert atmosphere;	70%
With triethylamine; copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In benzene at 20℃; for 20h;	63.9%

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) + methyl iodide (74-88-4) → (S)-4-hydroxy-3-methyl-2-(but-2-yn-1-yl)cyclopent-2-en-1-one

Conditions	Yield
With copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate; 1,3-bis(tert-butyl) imidazolium tetrafluoroborate In diethyl ether; N,N-dimethyl-formamide at 40 - 45℃; Inert atmosphere;	56%

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) + ethyl iodide (75-03-6) → (S)-4-hydroxy-3-methyl-2-(pent-2-yn-1-yl)cyclopent-2-en-1-one

Conditions	Yield
With copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate; 1,3-bis(tert-butyl) imidazolium tetrafluoroborate In diethyl ether; N,N-dimethyl-formamide at 40 - 45℃; Sonogashira Cross-Coupling; Inert atmosphere;	10%

N-acetylcystein (616-91-1) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → PGL-MA2

Conditions	Yield
With triethylamine at 20℃; for 16h; Addition;

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → PGL-SUL

Conditions	Yield
With chlorosulfonic acid In tetrachloromethane at 0℃; for 16h; Substitution;

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-(+)-pyrethrolone (487-67-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 63.9 percent / Et3N / Pd3P>4, CuI / benzene / 20 h / 20 °C 2: 85 percent / activated Zn / H2O; propan-1-ol / 30 h / Heating View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine / toluene / 16 h / 20 - 25 °C / Inert atmosphere 2: hydrogenchloride; zinc / ethanol; water / 16 h / 75 - 80 °C / Inert atmosphere View Scheme

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) + 1,2-dibromomethane (74-95-3) → (S)-2-methyl-4-methylidene-3-(2-propynyl)-cyclopent-2-ene-1-ol

Conditions	Yield
With sodium hydrogencarbonate; zinc; titanium tetrachloride In tetrahydrofuran; hexane; dichloromethane; water

(1R)-trans-3-[(1-E/Z)-2-cyano-2-(methylthio)ethenyl]-2,2-dimethylcyclopropanecarboxylic acid chloride (1332340-78-9) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-2-methyl-3-(2-propynyl)cyclopent-2-en-4-on-1-yl (1R)-trans-3-[(1E)-2-cyano-2-(methylthio)ethenyl]-2,2-dimethylcyclopropane carboxylate (1332340-73-4)

Conditions	Yield
With pyridine In toluene at 20℃; for 12h;

(1R)-trans-3-[(1Z, 3E)-2-cyano-1,3-pentadienyl]-2,2-dimethylcyclopropanecarboxylic acid chloride (1338068-76-0) + (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-2-methyl-3-(2-propynyl)cyclopent-2-en-4-on-1-yl (1R)-trans-3-[(1Z,3E)-2-cyano-1,3-pentadienyl]-2,2-dimethylcyclopropane carboxylate (1338068-77-1)

Conditions	Yield
Stage #1: (1R)-trans-3-[(1Z, 3E)-2-cyano-1,3-pentadienyl]-2,2-dimethylcyclopropanecarboxylic acid chloride; (S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one With pyridine In tetrahydrofuran at 20℃; for 12h; Stage #2: With hydrogenchloride In water

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S,Z)-2-(pent-2-en-1-yl)-4-hydroxy-3-methylcyclopent-2-en-1-one

Conditions	Yield
Multi-step reaction with 2 steps 1: 1,3-bis(tert-butyl) imidazolium tetrafluoroborate; copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate / N,N-dimethyl-formamide; diethyl ether / 40 - 45 °C / Inert atmosphere 2: quinoline; 5% palladium on barium sulphate; hydrogen / ethyl acetate / 20 - 25 °C View Scheme

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-3-((Z)-but-2-en-1-yl)-2-methyl-4-oxocyclopent-2-en-1-yl(1R,3R) -2,2-dimethyl-3-(2-methylprop-1-en-1-yl ) -cyclopropane-1-carboxylate (25402-06-6)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: 1,3-bis(tert-butyl) imidazolium tetrafluoroborate; copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate / N,N-dimethyl-formamide; diethyl ether / 40 - 45 °C / Inert atmosphere 2.1: quinoline; 5% palladium on barium sulphate; hydrogen / ethyl acetate / 20 - 25 °C 3.1: 1-methyl-1H-imidazole; p-toluenesulfonyl chloride / acetonitrile / 0.5 h / 0 - 5 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere View Scheme

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → (S)-2-methyl-4-oxo-3-((Z)-pent-2-en-1-yl)cyclopent-2-en-1-yl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-en-1-yl)-cyclopropane-1-carboxylate (4466-14-2)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: 1,3-bis(tert-butyl) imidazolium tetrafluoroborate; copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate / N,N-dimethyl-formamide; diethyl ether / 40 - 45 °C / Inert atmosphere 2.1: quinoline; 5% palladium on barium sulphate; hydrogen / ethyl acetate / 20 - 25 °C 3.1: 1-methyl-1H-imidazole; p-toluenesulfonyl chloride / acetonitrile / 0.5 h / 0 - 5 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere View Scheme

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → pyrethrin I (121-21-1)

Conditions

Yield

Multi-step reaction with 3 steps 1.1: copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine / toluene / 16 h / 20 - 25 °C / Inert atmosphere 2.1: hydrogenchloride; zinc / ethanol; water / 16 h / 75 - 80 °C / Inert atmosphere 3.1: 1-methyl-1H-imidazole; p-toluenesulfonyl chloride / acetonitrile / 0.5 h / 0 - 5 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere View Scheme

(S)-4-hydroxy-3-methyl-2-(2-propynyl)-cyclopent-2-ene-1-one (77087-34-4) → cinerin II (121-20-0)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 1,3-bis(tert-butyl) imidazolium tetrafluoroborate; copper(l) iodide; bis(η3-allyl-μ-chloropalladium(II)); caesium carbonate / N,N-dimethyl-formamide; diethyl ether / 40 - 45 °C / Inert atmosphere 2.1: quinoline; 5% palladium on barium sulphate; hydrogen / ethyl acetate / 20 - 25 °C 3.1: 1-methyl-1H-imidazole; p-toluenesulfonyl chloride; N-ethyl-N,N-diisopropylamine / acetonitrile / 0.5 h / 0 - 5 °C / Inert atmosphere 3.2: 2 h / 20 - 25 °C / Inert atmosphere 4.1: sodium dihydrogenphosphate; 2-methyl-but-2-ene; sodium chlorite / water; tert-butyl alcohol / 5 h / 20 - 25 °C 5.1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 20 - 25 °C / Inert atmosphere View Scheme

Upstream product

• 139107-32-7 C₉H₁₁BO₄ 
• 96189-00-3 (+/-)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one 
• 90428-87-8 (S)-4-acetoxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one 
• 94412-95-0 (R)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl nitrate 
• 95413-30-2 (R)-2-methyl-4-oxo-3-(2-propynyl)-2-cyclopentenyl methanesulfonate 
• 77832-42-9 (R)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one 

Downstream Products

• 487-67-2 (S)-(+)-pyrethrolone 
• 25402-06-6 (S)-3-((Z)-but-2-en-1-yl)-2-methyl-4-oxocyclopent-2-en-1-yl(1R,3R) -2,2-dimethyl-3-(2-methylprop-1-en-1-yl ) -cyclopropane-1-carboxylate 
• 121-21-1 pyrethrin I 
• 121-20-0 cinerin II 
• 1172-63-0 jasmolin II 
• 121-29-9 Pyrethrin II 
• 487-64-9 (R)-cinerolone 

Relevant articles and documents

Preparation of (4S)-4-hydroxy-3-methyl-2-(2′-propynyl)-2-cyclopentenone by combination of enzymatic hydrolysis and chemical transformation

(4S)-4-Hydroxy-3-methyl-2-(2′-propynyl)-2-cyclopentenone ((S)-2), which is an important alcohol moiety of optically active pyrethroid insecticides, was prepared from the corresponding racemic acetate ((±)-1) by the combination of enzymatic hydrolysis and chemical transformation in high chemical and optical yields.

Process for producing optically active cyclopentenolones

Optically active cyclopentenolones, which are useful as an intermediate of pyrethroid insecticides, are produced from racemic cyclopentenolones according to the following procedures; (1) asymmetric hydrolysis of racemic carboxylate esters of the cyclopentenolones, (2) nitrate- or sulfonate-esterification of the asymmetrical hydrolysis products, and (3) hydrolysis of the esterification products.