Isatoic anhydride

Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene.^[1]

Isatoic anhydride

Names
Preferred IUPAC name 2H-3,1-Benzoxazine-2,4(1H)-dione
Identifiers
CAS Number	118-48-9 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL346059
ChemSpider	8056
DrugBank	DB11593
ECHA InfoCard	100.003.869
EC Number	204-255-0
PubChem CID	8359
UNII	R8TFA74Y4U Y
CompTox Dashboard (EPA)	DTXSID6026955
InChI InChI=1S/C8H5NO3/c10-7-5-3-1-2-4-6(5)9-8(11)12-7/h1-4H,(H,9,11) Key: TXJUTRJFNRYTHH-UHFFFAOYSA-N
SMILES C1=CC=C2C(=C1)C(=O)OC(=O)N2
Properties
Chemical formula	C8H5NO3
Molar mass	163.132 g·mol−1
Appearance	white solid
Melting point	243 °C (469 °F; 516 K)
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H317, H319
Precautionary statements	P261, P264+P265, P272, P280, P302+P352, P305+P351+P338, P321, P333+P317, P337+P317, P362+P364, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Reactions

Hydrolysis gives carbon dioxide and anthranilic acid. Alcoholysis proceeds similarly, affording the ester:

C₆H₄C₂O₃NH + ROH → C₆H₄(CO₂R)(NH₂) + CO₂

Amines also effect ring-opening. Active methylene compounds and carbanions replace oxygen giving hydroxyquinolinone derivatives. Deprotonation followed by alkylation gives the N-substituted derivatives. Sodium azide gives the benzimidazolone via the isocyanate.^[2] Isatoic anhydride is used as a blowing agent in the polymer industry, an application that exploits its tendency to release CO₂.

Uses

Isatoic anhydride has been used as a precursor for the synthesis of methaqualone^[3] and related 4-quinazolinone-based pharmaceutical drugs, including:

1. Tioperidone
2. Tranilast
3. Pelanserin
4. Diproqualone
5. Antrafenine
6. SJ-733
7. Nicafenine
8. Molinazone
9. Cloperidone
10. SGB 1534

References

1. E. C. Wagner; Marion F. Fegley. (1947). "Isatoic anhydride". Org. Synth. 27: 45. doi:10.15227/orgsyn.027.0045.
2. Coppola, Gary M. (1980). "The Chemistry of Isatoic Anhydride". Synthesis. 7 (7): 505–36. doi:10.1055/s-1980-29110.
3. Etienne F. van Zyl (2001). "A survey of reported syntheses of methaqualone and some positional and structural isomers". Forensic Sci. Int. 122 (2–3): 142–149. doi:10.1016/S0379-0738(01)00484-4. PMID 11672968.