116384-56-6

Basic information

• Product Name: Diethyl [(2-chloroethoxy)methyl]phosphonate
• Synonyms: Diethyl [(2-chloroethoxy)methyl] phosphonate ;Diethyl [(2-chloroethoxy)methyl]phosphonate(A2);Diethyl [(2-chloroethoxy)methyl]phosphonat;116384-56-6
• CAS NO: 116384-56-6
• Molecular Formula: C₇H₁₆ClO₄P
• Molecular Weight: 230.626301
• EINECS: 1592732-453-0
• Mol File: 116384-56-6.mol
• Article Data: 6

Chemical Properties

• Boiling Point: 292.335 °C at 760 mmHg
• Flash Point: 164.17 °C
• Appearance: /
• Density: 1.161 g/cm³
• Vapor Pressure: 0.003mmHg at 25°C
• Refractive Index: 1.431
• CAS DataBase Reference: Diethyl [(2-chloroethoxy)methyl]phosphonate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl [(2-chloroethoxy)methyl]phosphonate(116384-56-6)
• EPA Substance Registry System: Diethyl [(2-chloroethoxy)methyl]phosphonate(116384-56-6)

Safety Data

• Hazardous Substances Data: 116384-56-6(Hazardous Substances Data)

Usage

General Description

Diethyl [(2-chloroethoxy)methyl]phosphonate, also known as Sarin, is a highly toxic organophosphorus compound that is primarily used as a chemical warfare agent. It is a colorless, odorless liquid that is easily vaporized and can be absorbed through the skin, eyes, and respiratory system. Upon exposure, it can cause a range of symptoms including nausea, vomiting, convulsions, respiratory distress, and ultimately death. Due to its toxic and lethal effects, it is considered a potent chemical weapon and is prohibited under the Chemical Weapons Convention. Its production and use are closely monitored and regulated by international authorities.

InChI:InChI=1/C7H16ClO4P/c1-3-11-13(9,12-4-2)7-10-6-5-8/h3-7H2,1-2H3

Synthetic route

2-chloroethyl chloromethyl ether (1462-33-5) + triethyl phosphite (122-52-1) → 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6)

Conditions	Yield
at 125 - 140℃; for 4h; Arbuzov Reaction;	100%
at 125℃; Arbuzov reaction;	82%
at 110℃; for 7h;
at 80℃; for 3h; Neat (no solvent);

diethyl 2-hydroxyethoxymethanephosphonate (116384-55-5) → 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6)

Conditions	Yield
With tetrachloromethane; triphenylphosphine for 4h; Heating;	50%

2-chloroethyl chloromethyl ether (1462-33-5) + triethyl phosphite (122-52-1) → methylene chloride (74-87-3) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6)

Conditions	Yield
1) 90 min at 90 deg C 2) 4 h at 125 deg C; Yield given;

2-((diethoxyphosphoryl)methoxy)ethyl acetate (100708-15-4) → 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 99 percent / Dowex 50X8 (H(+)-form) / ethanol / 30 h / Heating 2: 50 percent / CCl4, triphenylphosphine / 4 h / Heating View Scheme

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → 4-chloro-2-oxabutanyl-1-phosphonic acid (1391871-33-2)

Conditions	Yield
With trimethylsilyl bromide In acetonitrile at 20℃; Inert atmosphere;	100%

ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate (123237-03-6, 5395-36-8) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → C21H31N2O7P (1442461-39-3)

Conditions	Yield
Stage #1: ethyl 6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	92%
With potassium carbonate In acetonitrile at 20 - 85℃;

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + nifetepimine (123371-44-8) → C21H30N3O9P (1442461-32-6)

Conditions	Yield
Stage #1: nifetepimine With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	92%
With potassium carbonate In acetonitrile at 20 - 85℃;

5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidine-2(1H)-thione (123043-88-9, 33458-26-3) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → C21H31N2O6PS

Conditions	Yield
Stage #1: 5-ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyrimidine-2(1H)-thione With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	90%

ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (123629-41-4) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → ethyl 3-(2-((diethoxyphosphoryl)methoxy)ethyl)-4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (1442461-41-7)

Conditions	Yield
Stage #1: ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	85%
With potassium carbonate In N,N-dimethyl-formamide; acetonitrile at 20 - 85℃; for 20h;

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 5-ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione → C21H31N2O7PS

Conditions	Yield
Stage #1: 5-ethoxycarbonyl-6-methyl-4-(4-hydroxyphenyl)-3,4-dihydropyrimidin-2(1H)-thione With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	85%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 6-methyl-4-(4-nitro-phenyl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester → C21H30N3O8PS

Conditions	Yield
Stage #1: 6-methyl-4-(4-nitro-phenyl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	85%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + ethyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate (123371-45-9) → C21H30N3O9P (1442461-31-5)

Conditions	Yield
Stage #1: ethyl 6-methyl-4-(4-nitrophenyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	83%
With potassium carbonate In acetonitrile at 20 - 85℃;

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + ethyl 6-methyl-4-(3-nitrophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate (914915-59-6) → C21H30N3O8PS

Conditions	Yield
Stage #1: ethyl 6-methyl-4-(3-nitrophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	83%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → O,O‐diethyl 2-iodoethoxymethylphosphonate

Conditions	Yield
With sodium iodide In acetone for 24h; Finkelstein Reaction; Reflux; Green chemistry;	83%
With potassium iodide In tetrahydrofuran at 45℃; for 1h;

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + ethyl 4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (5937-24-6) → C21H30FN2O7P

Conditions	Yield
Stage #1: ethyl 4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	82%

ethyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (5948-68-5) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → C21H31N2O8P (1442461-33-7)

Conditions	Yield
Stage #1: ethyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	80%
With potassium carbonate In acetonitrile at 20 - 85℃;

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + ethyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-thioxopyrimidine-5-carboxylate (5948-74-3) → C21H31N2O7PS

Conditions	Yield
Stage #1: ethyl 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-thioxopyrimidine-5-carboxylate With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	80%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (74936-72-4) → C23H31N2O10P

Conditions	Yield
Stage #1: 5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	78%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 4-(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (201287-93-6) → ethyl 3-(2-((diethoxyphosphoryl)methoxy)ethyl)-4-(4-fluorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Conditions	Yield
Stage #1: 4-(4-fluoro-phenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester With potassium carbonate In acetonitrile at 20℃; Inert atmosphere; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In acetonitrile at 20 - 85℃; Inert atmosphere;	77%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → diethyl <(2-azidoethoxy)methyl>phosphonate (160713-48-4)

Conditions	Yield
With sodium azide; tetrabutylammomium bromide In toluene at 90℃; for 4h;	73%
With sodium azide; tetrabutylammomium bromide In toluene at 90℃; for 4h;	68%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + potassium phtalimide (1074-82-4) → [2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethoxymethyl]-phosphonic acid diethyl ester (212894-83-2)

Conditions	Yield
In N,N-dimethyl-formamide at 120℃; for 7h;	73%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 6-methylthiopurine (50-66-8) → [2-(6-Methylsulfanyl-purin-9-yl)-ethoxymethyl]-phosphonic acid diethyl ester (126354-37-8)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1)At 50 deg C for 1 h 2) addition of IIb,50 deg C for 22 h;	71%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 2-Amino-6-chloropurin (10310-21-1) → 2-amino-6-chloro-9-[2-(phosphonomethoxy)ethyl]purine bisethyl ester (126354-43-6) + 7-(2-Diethoxyphosphonylmethoxyethyl)-2-amino-6-chloropurine (126354-44-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	A 64% B 12%

2-benzyl-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide (72357-88-1) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → C21H27N2O7PS

Conditions	Yield
With sodium hydride; potassium iodide In N,N-dimethyl-formamide at 80℃; Cooling with ice;	60%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 2,6-diaminopurine (1904-98-9) → [2-(2,6-Diamino-purin-9-yl)-ethoxymethyl]-phosphonic acid diethyl ester (119742-08-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1) 80 deg C for 1 h 2) After addition IIb 80 deg C for 24 h;	58%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + 4H-benzo[e][1,2,4]thiadiazine-1,1-dioxide (359-85-3) → C14H21N2O6PS

Conditions	Yield
Stage #1: 4H-benzo[e][1,2,4]thiadiazine-1,1-dioxide With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Cooling with ice; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester With potassium iodide In N,N-dimethyl-formamide; mineral oil at 50℃;	49%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) + adenine (66224-66-6, 66224-67-7, 66224-68-8, 66224-69-9, 134434-48-3, 134434-49-4, 134454-76-5, 134461-75-9) → [[2-(6-amino-9H-purine-9-yl)ethoxy]methyl]phosphonic acid diethyl ester (116384-53-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 80℃; for 15h;	46%
Stage #1: adenine With potassium carbonate In N,N-dimethyl-formamide at 25 - 85℃; for 1h; Stage #2: 2-chloroethoxymethyl phosphonic acid diethyl ester In N,N-dimethyl-formamide for 20h;
With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 80℃; for 5h;

4-methoxy-5-methyl-pyrimidin-2(1H)-one (25902-89-0) + 2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → [2-(4-Methoxy-5-methyl-2-oxo-2H-pyrimidin-1-yl)-ethoxymethyl]-phosphonic acid diethyl ester (126354-57-2)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1) 80 deg C for 1 h b) addition of IIb,100 deg C for 15 h;	45%

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → O,O-diethyl (2-aminoethoxy)methylphosphonate (160713-49-5)

Conditions	Yield
Stage #1: 2-chloroethoxymethyl phosphonic acid diethyl ester With sodium azide; tetramethylammonium bromide In toluene at 70℃; Stage #2: With triphenylphosphine In toluene at 20℃;
Multi-step reaction with 2 steps 1: 73 percent / dimethylformamide / 7 h / 120 °C 2: hydrazine / ethanol / 1 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 68 percent / tetrabutylammonium bromide, sodium azide / toluene / 4 h / 90 °C 2: 75 percent / triphenylphosphine / toluene / 1 h / Ambient temperature View Scheme

2-chloroethoxymethyl phosphonic acid diethyl ester (116384-56-6) → 6-ethyl>amino>-2(1H)-amino-5-nitropyrimidin-4(3H)-one (160713-50-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaN3; N(CH3)4Br / toluene / 70 °C 1.2: Ph3P / toluene / 20 °C 2.1: 65 percent / acetone; methanol / 24 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1: 68 percent / tetrabutylammonium bromide, sodium azide / toluene / 4 h / 90 °C 2: 75 percent / triphenylphosphine / toluene / 1 h / Ambient temperature 3: 50.2 percent / acetone / 12 h / Ambient temperature View Scheme

Upstream product

• 1462-33-5 2-chloroethyl chloromethyl ether 
• 122-52-1 triethyl phosphite 
• 100708-15-4 2-((diethoxyphosphoryl)methoxy)ethyl acetate 
• 116384-55-5 diethyl 2-hydroxyethoxymethanephosphonate 

Downstream Products

• 116384-53-3 [[2-(6-amino-9H-purine-9-yl)ethoxy]methyl]phosphonic acid diethyl ester 
• 374678-38-3 7-[2-(diethoxyphosphorylmethoxy)ethyl]adenine 
• 1434271-17-6 diethyl {2-[4-(2,4-difluorophenyl)-1H-1,2,3-triazol-1-yl]ethoxy}methylphosphonate 
• 1434271-16-5 diethyl {2-[4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl]ethoxy}methylphosphonate 
• 1434271-15-4 diethyl {2-[4-(2-fluorophenyl)-1H-1,2,3-triazol-1-yl]ethoxy}methylphosphonate 
• 116384-54-4 Ethyl Ester of 9-(2-Phosphonylmethoxyethyl)adenine 

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