1-Chloroethyl chloroformate Property

Melting point:

-65°C

Boiling point:

118-119 °C (lit.)

Density 

1.325 g/mL at 25 °C (lit.)

vapor pressure 

3.25 psi ( 20 °C)

refractive index 

n20/D 1.422(lit.)

Flash point:

105 °F

storage temp. 

2-8°C

solubility 

Miscible with most organic solvents.

form 

Liquid

color 

Clear colorless

Sensitive 

Moisture Sensitive

BRN 

1747601

Stability:

Hygroscopic, Moisture Sensitive

InChIKey

QOPVNWQGBQYBBP-UHFFFAOYSA-N

CAS DataBase Reference

50893-53-3(CAS DataBase Reference)

NIST Chemistry Reference

«ALPHA»-chloroethyl chloroformate(50893-53-3)

Safety

Hazard Codes 

T

Risk Statements 

10-22-23-34

Safety Statements 

26-36/37/39-45

RIDADR 

UN 2742 6.1/PG 2

WGK Germany 

3

F 

10-19-21

TSCA 

No

HazardClass 

6.1

PackingGroup 

II

HS Code 

29159000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H226Flammable liquid and vapour

H302Harmful if swallowed

H314Causes severe skin burns and eye damage

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P233Keep container tightly closed.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

1-Chloroethyl chloroformate Chemical Properties,Usage,Production

Chemical Properties

Clear and colorless liquid

Uses

Reagent for the selective N-dealkylation of tertiary amines in high yields.

Uses

1-Chloroethyl chloroformate was used:

• for N-demethylation reaction during determination of multiple drugs of abuse in biological fluids using capillary electrophoresis with native fluorescence and laser-induced fluorescence detection
• as catalyst in chemoselective desilylation of silyl-protected alcohols
• as reagent in N-demethylation of tertiary amines to produce drug metabolite reference material for forensic toxicological applications
• as reagent to cleave benzhydryl groups from amines

Preparation

1-Chloroethyl chloroformate is obtained by stirring phosgene and acetaldehyde in the presence of benzyltributylammonium chloride, followed by distillation (96% yield).

Reactivity Profile

1-chloroethyl chloroformate was found to be the potential reagent of choice for the N-demethylation of tertiary amines. The reaction was performed by refluxing in dry 1,2-dichloroethane under nitrogen, and the carbamate intermediate was hydrolysed by treatment with methanol[1].

The debenzylation conditions were mediated by 1-chloroethyl chloroformate (green), which gave the expected secondary amine 3 (blue) an excellent yield. The debenzylation proceeds presumably via a carbamate intermediate following the reaction of the starting material 6 with 1-chloroethyl chloroformate and loss of benzyl chloride. Subsequent decarboxylation, promoted by excess methanol and reflux conditions, produced the desired secondary amine 3.

Synthesis

An initiator solution was formed by dissolving 0.33 gram of 2,2'-azobis(2-methylpropanenitrile) in 61 grams of ethyl chloroformate. The initiator solution was charged to the syringe. The flask was charged with 590 grams of ethyl chloroformate. The flask was then heated to obtain close to maximum reflux without flooding. The syringe pump was set to feed approximately 5 millilitres of the initiator solution per hour. The introduction of molecular chlorine gas through the first inlet at 0.47 gram per minute was then begun. During the reaction, the condenser functioned as a total reflux condenser. The chlorine introduction was terminated twelve hours later, and the reaction mixture was allowed to cool. The final reaction product weighed 806 grams. Gas chromatographic analysis of the reaction product showed it to contain 18.8 area percent of ethyl chloroformate, 45.4 area percent of 1-chloroethyl chloroformate, 34.7 area percent of 2-chloroethyl chloroformate, and 1.06 area percent of dichlorinated ethyl chloroformate.

References

[1] Anna Pelander, Tapio A. Hase, Ilkka Ojanper? . “Preparation of N-demethylated drug metabolites for analytical purposes using 1-chloroethyl chloroformate.” Forensic science international 85 3 (1997): Pages 193-198.
[2] Katrina A Badiola. “Efficient Synthesis and Anti-Tubercular Activity of a Series of Spirocycles: An Exercise in Open Science.” PLoS ONE (2014): e111782.