59702-31-7

Basic information

• Product Name: N-Ethyl-2,3-dioxopiperazine
• Synonyms: N-ETHYLPIPERAZINE-2,3-DIONE;N-ETHYL-2,3-DIKETOPIPERAZINE;N-ETHYL-2,3-DIOXOPIPERAZINE;N-Ethyl-2,3-diketonepiperazine;N-ETHYLPIPERAZINE-2 3-DIONE 97%;1-Ethylpiperazine-2,3-dione,98+%;N-Ethyl-2,3-dioxopiperazine, 98+%;n-ethylpiperizine-2,3-dione
• CAS NO: 59702-31-7
• Molecular Formula: C₆H₁₀N₂O₂
• Molecular Weight: 142.16
• EINECS: 261-866-5
• Product Categories: Piperaizine;Heterocyclic Compounds;Building Blocks;Heterocyclic Building Blocks;Piperazines;Heterocycles;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 59702-31-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 106-110 °C(lit.)
• Boiling Point: 259.72°C (rough estimate)
• Appearance: white to pale yellow crystalline powder
• Density: 0.64
• Refractive Index: 1.5010 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: 2000 g/L
• PKA: 12.57±0.20(Predicted)
• Water Solubility: 2000 g/L
• BRN: 879076
• CAS DataBase Reference: N-Ethyl-2,3-dioxopiperazine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Ethyl-2,3-dioxopiperazine(59702-31-7)
• EPA Substance Registry System: N-Ethyl-2,3-dioxopiperazine(59702-31-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-37
• WGK Germany: 3
• RTECS: TL6380250
• Hazardous Substances Data: 59702-31-7(Hazardous Substances Data)

Usage

Chemical Properties

1-Ethyl-2,3-dioxopiperazine is WHITE TO PALE YELLOW CRYSTALLINE POWDER

Uses

Different sources of media describe the Uses of 59702-31-7 differently. You can refer to the following data:
1. 1-Ethyl-2,3-dioxopiperazine is an intermediate used in the new process for the synthesis of Piperacillin sodium.
2. 1-Ethyl-2,3-dioxopiperazine (Piperacillin EP Impurity E; Piperacillin USP Related Compound E) is an intermediate used in the new process for the synthesis of Piperacillin sodium.

InChI:InChI=1/C6H10N2O2/c1-2-8-4-3-7-5(9)6(8)10/h2-4H2,1H3,(H,7,9)

Synthetic route

N-ethylethane-1,2-diamine (110-72-5) + oxalic acid diethyl ester (95-92-1) → 1-ethyl-2,3-dioxo-piperazine (59702-31-7)

Conditions	Yield
With acetic acid In methanol at 15 - 50℃; for 1h; Reagent/catalyst;	83.21%

6-<(+/-)-α-amino-α-(2-aminothiazol-4-yl)acetamido>penicillanic acid (85208-10-2) + 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3) → 6-<(+/-)-α-(2-aminothiazol-4-yl)-α-(4-ethyl-2,3-dioxopiperazin-1-ylcarbonylamino)acetamido>penicillanic acid (85208-19-1, 85208-20-4, 85280-44-0) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7)

Conditions	Yield
With sodium hydrogencarbonate 1.) THF, H2O, 0 deg C, 2.) pH=7-7.5, room temperature, 1 h;	A 21% B n/a

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 1-ethyl-4-(mercaptomethyl)-piperazine-2,3-dione + 1-ethyl-4-(hydroxymethyl)-piperazine-2,3-dione

Conditions	Yield
With potassium hydroxide In formaldehyd	A 100% B n/a

bis(trichloromethyl) carbonate (32315-10-9) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3)

Conditions	Yield
With pyridine; dmap; chloro-trimethyl-silane In dichloromethane at -25 - -20℃;	94.3%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 10 - 20℃; for 1.06667h; Temperature; Reagent/catalyst; Green chemistry;	93.9%
Stage #1: 1-ethyl-2,3-dioxo-piperazine With chloro-trimethyl-silane; triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere; Schlenk technique; Stage #2: bis(trichloromethyl) carbonate In dichloromethane at -30℃; Inert atmosphere; Schlenk technique;

bis(trichloromethyl) carbonate (32315-10-9) + C13H17NO4 + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C20H25N3O7

Conditions	Yield
Stage #1: 1-ethyl-2,3-dioxo-piperazine With chloro-trimethyl-silane; triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice; Stage #2: bis(trichloromethyl) carbonate In dichloromethane at -30℃; for 1h; Stage #3: C13H17NO4 With chloro-trimethyl-silane; triethylamine In dichloromethane at -40℃; for 1.5h; Cooling with ice;	86%

bis(trichloromethyl) carbonate (32315-10-9) + C10H15N3O4S + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C17H23N5O7S

Conditions	Yield
Stage #1: 1-ethyl-2,3-dioxo-piperazine With chloro-trimethyl-silane; triethylamine In dichloromethane at 20℃; for 1h; Cooling with ice; Stage #2: bis(trichloromethyl) carbonate In dichloromethane at -30℃; for 1h; Stage #3: C10H15N3O4S With chloro-trimethyl-silane; triethylamine In dichloromethane at -40 - 20℃; for 2.5h; Cooling with ice;	86%

5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-bromobutyl)-3-methyl-1H-indole + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 1-ethyl-4-{4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indol-1-yl]butyl}piperazinedione

Conditions	Yield
Stage #1: 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-bromobutyl)-3-methyl-1H-indole; 1-ethyl-2,3-dioxo-piperazine With triethylamine In butan-1-ol for 4h; Reflux; Stage #2: With palladium 10% on activated carbon In ethyl acetate; ethanethiol; butan-1-ol at 45℃; for 24h;	49.1%

5,5'-diallyl-3-(chloromethyl)[1,1'-biphenyl]-2,2'-diol + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 1-((5,5'-diallyl-2,2'-dihydroxy-[1,1'-biphenyl]-3-yl)methyl)-4-ethylpiperazine-2,3-dione

Conditions	Yield
With caesium carbonate; potassium iodide In acetonitrile at 80℃;	31.1%

chloro-trimethyl-silane (75-77-4) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 1-Ethyl-4-trimethylsilanyl-piperazine-2,3-dione

Conditions	Yield
With triethylamine In chloroform for 1h; Heating;
With triethylamine In dichloromethane at -10 - 0℃; for 0.2h; Solvent; Reagent/catalyst;

ethyl (4-benzothiazol-2-ylbenzyl)phosphonochloridate hydrochloride (104608-47-1) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → (4-Benzothiazol-2-yl-benzyl)-(4-ethyl-2,3-dioxo-piperazin-1-yl)-phosphinic acid ethyl ester (127881-48-5)

Conditions	Yield
Yield given. Multistep reaction;

tert-butyl 3-bromopropionate (55666-43-8) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 3-(4-ethyl-2,3-dioxo-piperazin-1-yl)propionic acid tert-butyl ester (610311-90-5)

Conditions	Yield
With polystyrene-bound 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine In acetonitrile at 22℃; for 16h; Polystyrene;

[2-(4-(bromomethyl)phenyl)ethyl]carbamic acid tert-butyl ester (914103-95-0) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 1-[4-(2-aminoethyl)benzyl]-4-ethylpiperazine-2,3-dione hydrochloride (914104-05-5)

Conditions	Yield
Stage #1: [2-(4-(bromomethyl)phenyl)ethyl]carbamic acid tert-butyl ester; 1-ethyl-2,3-dioxo-piperazine With sodium hydride In N,N-dimethyl-formamide at 1 - 30℃; for 1h; Stage #2: With potassium hydrogensulfate; water; sodium hydrogencarbonate In ethyl acetate; N,N-dimethyl-formamide Stage #3: With hydrogenchloride In ethyl acetate at 1 - 30℃; for 1h;

5-chloro-N-((1-(4-iodophenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide (945559-61-5) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 5-chloro-N-((1-(4-(4-ethyl-2,3-dioxopiperazin-1-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide

Conditions	Yield
With potassium carbonate; N,N`-dimethylethylenediamine; copper(l) iodide In 1,4-dioxane; dimethyl sulfoxide at 110℃;

bromoacetic acid tert-butyl ester (5292-43-3) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → (4-ethyl-2, 3-dioxo-piperazin-1-yl)-acetic acid (488846-73-7)

Conditions	Yield
With potassium carbonate In tert-butyl alcohol

phosgene (75-44-5) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride (59703-00-3)

Conditions	Yield
With chloro-trimethyl-silane; triethylamine In tetrahydrofuran; 1,4-dioxane

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → sodium 4-ethyl-2,3-dioxopiperazine

Conditions	Yield
With 1H-imidazole; sodium In 1,2-dimethoxyethane for 10h; Solvent; Reagent/catalyst; Reflux; Industrial scale;

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → (4-ethyl-2, 3-dioxo-piperazin-1-yl)-acetic acid (488846-73-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 20 °C / Inert atmosphere 1.2: 3 h / 20 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 1.5 h / 20 °C View Scheme

bromoacetic acid tert-butyl ester (5292-43-3) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → tert-butyl 2-(4-ethyl-2,3-dioxopiperazin-1-yl)acetate

Conditions	Yield
Stage #1: 1-ethyl-2,3-dioxo-piperazine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Inert atmosphere; Stage #2: bromoacetic acid tert-butyl ester In N,N-dimethyl-formamide; mineral oil at 20℃; for 3h; Inert atmosphere;	940 mg

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → piperacillin (61477-96-1, 64131-97-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: dichloromethane / 0.5 h / 5 °C 2.1: 0.1 h / 8 °C / 1500.15 Torr / Inert atmosphere 3.1: dichloromethane 3.2: 0.67 h / 3 °C 4.1: water / 0.67 h / 6 - 9 °C / Large scale View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C26H35N5O7SSi

Conditions	Yield
Multi-step reaction with 3 steps 1.1: dichloromethane / 0.5 h / 5 °C 2.1: 0.1 h / 8 °C / 1500.15 Torr / Inert atmosphere 3.1: dichloromethane 3.2: 0.67 h / 3 °C View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C10H17ClN2O3Si

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 0.5 h / 5 °C 2: 0.1 h / 8 °C / 1500.15 Torr / Inert atmosphere View Scheme

chloro-trimethyl-silane (75-77-4) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C9H18N2O2Si

Conditions	Yield
In dichloromethane at 5℃; for 0.5h;

2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester (30925-18-9) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → benzyl (S)-2-((tert-butoxycarbonyl)amino)-4-(ethyl-2,3-dioxopiperazin-1-yl)-4-oxobutanoate

Conditions	Yield
Stage #1: 2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester With triethylamine; HATU In dichloromethane at 20℃; for 0.5h; Stage #2: 1-ethyl-2,3-dioxo-piperazine In dichloromethane at 20℃; for 1h;	5.64 g

2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester (30925-18-9) + 1-ethyl-2,3-dioxo-piperazine (59702-31-7) → (S)-2-((tert-butoxycarbonyl)amino)-4-(4-ethyl-2,3-dioxopiperazin-1-yl)-4-oxobutanoic acid

Conditions	Yield
Multi-step reaction with 2 steps 1.1: HATU; triethylamine / dichloromethane / 0.5 h / 20 °C 1.2: 1 h / 20 °C 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 18 h / 20 °C View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C15H12(2)H5N3O5

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 1.2: -30 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.2: 1.5 h / -40 - 0 °C / Inert atmosphere; Schlenk technique View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C30H28(2)H5N5O7S

Conditions

Yield

Multi-step reaction with 3 steps 1.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 1.2: -30 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.2: 1.5 h / -40 - 0 °C / Inert atmosphere; Schlenk technique 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere; Schlenk technique 3.2: 3 h / 0 - 20 °C / Inert atmosphere; Schlenk technique View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C34H39(2)H5N6O7S + C34H39(2)H5N6O7S

Conditions

Yield

Multi-step reaction with 4 steps 1.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 1.2: -30 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.2: 1.5 h / -40 - 0 °C / Inert atmosphere; Schlenk technique 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere; Schlenk technique 3.2: 3 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 4.1: acetonitrile / 2 h / 20 °C / Inert atmosphere; Schlenk technique View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → piperacillin-D5

Conditions

Yield

Multi-step reaction with 4 steps 1.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 1.2: -30 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.2: 1.5 h / -40 - 0 °C / Inert atmosphere; Schlenk technique 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere; Schlenk technique 3.2: 3 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 4.1: palladium on activated carbon; hydrogen / tetrahydrofuran; water / 1 h / 20 °C / 760.05 Torr / Schlenk technique View Scheme

1-ethyl-2,3-dioxo-piperazine (59702-31-7) → C27H33(2)H5N6O7S + C27H33(2)H5N6O7S

Conditions

Yield

Multi-step reaction with 5 steps 1.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 1 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 1.2: -30 °C / Inert atmosphere; Schlenk technique 2.1: triethylamine; chloro-trimethyl-silane / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.2: 1.5 h / -40 - 0 °C / Inert atmosphere; Schlenk technique 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 0.08 h / 0 °C / Inert atmosphere; Schlenk technique 3.2: 3 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 4.1: acetonitrile / 2 h / 20 °C / Inert atmosphere; Schlenk technique 5.1: palladium on activated carbon; hydrogen / tetrahydrofuran; water / 1 h / 20 °C / 760.05 Torr / Schlenk technique View Scheme

Upstream product

• 85208-10-2 6-<(+/-)-α-amino-α-(2-aminothiazol-4-yl)acetamido>penicillanic acid 
• 59703-00-3 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride 
• 110-72-5 N-ethylethane-1,2-diamine 
• 95-92-1 oxalic acid diethyl ester 

Downstream Products

• 59703-00-3 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride 
• 61477-96-1 piperacillin 
• 488846-73-7 (4-ethyl-2, 3-dioxo-piperazin-1-yl)-acetic acid 
• 914104-05-5 1-[4-(2-aminoethyl)benzyl]-4-ethylpiperazine-2,3-dione hydrochloride 
• 127881-48-5 (4-Benzothiazol-2-yl-benzyl)-(4-ethyl-2,3-dioxo-piperazin-1-yl)-phosphinic acid ethyl ester 

Relevant articles and documents

Synthetic method of N-ethyl-2,3-dioxygen piperazine

The invention relates to a synthetic method of N-ethyl-2,3-dioxygen piperazine, belonging to the technical fields of pharmaceutical and chemical industry. The synthetic method comprises the steps of preparing a mixed solution A from N-ethyl ethanediamine and absolute methanol, adding a catalyst and diethyl oxalate into absolute methanol, and uniformly stirring, so as to obtain a solution B. Compared with the prior art, the synthetic method of N-ethyl-2,3-dioxygen piperazine has the advantages that the raw materials are easily available, the operation is simple, conditions are mild, the quality is stable, and the energy consumption is low; and the synthetic method is environment-friendly and has very good industrial prospects and promotional values.

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