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

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

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

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.

The Chemistry of Some 2-Aminothiazol-4-ylacetic Acid Derivatives and the Synthesis of Derived Penicillins

The N-protected 2-aminothiazol-4-ylacetic acid derivatives (6), (11), (14), (16), (18), (26), (27), (30), (33), and (34) have been prepared.They are readily available by reaction of the corresponding 2-aminoethyl esters such as (1) with the appropriate acylating agents, generally giving a bis-carbamate of type (5), followed by saponification.The process is general for α-methylene, α-oximino, and α-aminosubstituents in the side-chain affording in the last case a route to differentially protected α-amino-α-(2-aminothiazol-4-yl)acetic acids such as (30).The optimum conditions for the acylations are described; the course of the saponification of the bis-carbamate esters is discussed and physical evidence for the structures of the derivatives is presented.The use of the protected acids (11) and (34) in the synthesis of the piperacillin analogue (38) is described.

Novel penicillins and cephalosporins and process for producing the same

Novel penicillins and cephalosporins and non-toxic salts thereof, which contain a mono- or di-oxo- or thioxo-piperazino(thio)carbonylamino group in molecule. These compounds are valuable antibacterial compounds for use in mammals including man. This disclosure relates to such compounds and a process for the preparation thereof.

Novel penicillins and cephalosporins and process for producing the same

Novel penicillins and cephalosporins and non-toxic salts thereof, which contain a mono- or di-oxo- or thioxo-piperazino(thio)carbonylamino group have been prepared. These compounds are valuable antibacterial compounds for use in mammals including man. A process for the preparation of the compounds has also been discovered.