4-Chloro-isatoic anhydride

4-Chloro-isatoic anhydride Property

Melting point:

255-259 °C

Density 

1.540±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

solubility 

soluble in Dimethylformamide

form 

powder to crystal

pka

9.95±0.20(Predicted)

color 

White to Light yellow

CAS DataBase Reference

40928-13-0(CAS DataBase Reference)

Safety

Hazard Codes 

Xn

Risk Statements 

22-36/37/38

Safety Statements 

26-36/37

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

2934999090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

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

P302+P352IF ON SKIN: wash with plenty of soap and water.

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

4-Chloro-isatoic anhydride Chemical Properties,Usage,Production

Chemical Properties

White solid

Synthesis Reference(s)

The Journal of Organic Chemistry, 26, p. 613, 1961 DOI: 10.1021/jo01061a618

Synthesis

General procedure for the synthesis of 7-chloro-1H-benzo[d][1,3]oxazine-2,4-dione from triphosgene and 2-amino-4-chlorobenzoic acid: 1. Preparation of Intermediate G: To a stirred solution of 2-amino-4-chlorobenzoic acid (10 g, 0.058 mol) in acetonitrile (60 mL), a solution of pyridine (9.4 mL, 0.117 mol, 2 eq.) and triphosgene (17.3 g, 0.058 mol, 1 eq.) in dichloromethane (85 mL, 0.7 M) was slowly added. 2. Treatment of the reaction mixture: the resulting orange reaction solution was heated at 50 °C for 2 h and subsequently cooled to room temperature. 3. Separation and purification: the reaction solution was diluted with water (50 mL) to separate the organic and aqueous layers. The aqueous layer was extracted with dichloromethane (3 x 50 mL) and the combined organic layers were washed once with brine (50 mL) and dried with anhydrous magnesium sulfate. 4. Purification of products: The reaction solution was heated at 50 °C for 2 h and subsequently cooled to room temperature. 4. Purification of product: The solvent was removed by distillation under reduced pressure to give a yellow solid. The solid was recrystallized from hexane to give 7-chloro-1H-benzo[d][1,3]oxazine-2,4-dione (9.1 g, 74% yield) as a yellow solid. 1H NMR (acetone-d6, 500 MHz): δ (ppm) 7.13-7.14 (1H, s), 7.28-7.30 (1H, d, J = 8.5 Hz), 7.90-7.92 (1H, d, J = 8.6 Hz), 11.84 (1H, bs).

References

[1] Journal of Medicinal Chemistry, 2015, vol. 58, # 17, p. 6928 - 6937
[2] Journal of Medicinal Chemistry, 2006, vol. 49, # 7, p. 2311 - 2319
[3] Patent: US9126978, 2015, B2. Location in patent: Page/Page column 57; 58
[4] European Journal of Medicinal Chemistry, 1994, vol. 29, # 12, p. 925 - 940
[5] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 10, p. 2295 - 2299