Chemical Properties
off-white to light yellow-brown powder. Soluble in hot alcohol, hot acetic acid and acetone, insoluble in water.
Uses
4-Nitrophthalic anhydride is used an an intermediate for the synthesis of a benzimidazole PARP inhibitor I (succinate salt) (ABT-472).
Uses
5-Nitrophthalic Anhydride is used in the preparation of phthalic acids as well as compounds with anticonvulsant activities.
Preparation
4-Nitrophthalic anhydride is synthesized by hydrolysis of 4-nitrophthalimide and then dehydration. The 4-nitrophthalimide was added to the sodium hydroxide solution, heated and boiled for 15min. Adjust pH to 6-8 with nitric acid, and add nitric acid to boil for 5 min. Cooling, filtering, the filtrate was extracted with ether, the extract was dried and then the ether was evaporated, that is, 4-Nitrophthalic anhydride crystals were precipitated. Yield 95%.
General Description
Yellow powder.
Air & Water Reactions
Reacts with water. The organic acids produced by this reaction are significantly more soluble in water.
Reactivity Profile
4-Nitrophthalic anhydride reacts exothermically with water. The reactions are usually slow, but might become violent if local heating accelerates their rate. Acids accelerate the reaction with water. Incompatible with acids, strong oxidizing agents, alcohols, amines, and bases.
Fire Hazard
Flash point data for 4-Nitrophthalic anhydride are not available, however 4-Nitrophthalic anhydride is probably combustible.
Synthesis
General procedure for the synthesis of 4-nitrophthalic anhydride from 4-nitrophthalic acid: general method: 4-nitrophthalic acid (1 mmol) was mixed with oxalyl chloride (1.2 mmol) in anhydrous toluene (5 mL), and a drop of freshly distilled DMF was added as catalyst. After the reaction vessel was purged with argon, the reaction mixture was heated under stirring for 3 hours. Upon completion of the reaction, stirring was stopped and the toluene solution was decanted from the oily residue and filtered. The volatiles were removed by evaporation to give analytically pure 4-nitrophthalic anhydride. If further purification is desired, it may be converted to a crystalline form by grinding with diethyl ether. In some cases (see ESI), an additional crystallization step or grinding with a 1:2 (v/v) hexane-toluene mixture may be used to improve the purity of the product.
Purification Methods
Distil the anhydride in a vacuum and/or recrystallise it from *C6H6 or Et2O/pet ether. Dry it in vacuo. It forms addition compounds with anthracene (m 118o), and phenanthrene (m 96o). [Beilstein 17 III/IV 6150, 17/11 V 267.]
Precautions
Moisture Sensitive. Store away from strong bases and oxidizing agents. Incompatible with water, bases, strong acids and oxidizing agents.
References
[1] Patent: US3979416, 1976, A
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1994, # 20, p. 2967 - 2974
[3] Chemical and Pharmaceutical Bulletin, 1994, vol. 42, # 9, p. 1817 - 1821
[4] Tetrahedron Letters, 2017, vol. 58, # 32, p. 3160 - 3163
[5] Bulletin des Societes Chimiques Belges, 1996, vol. 105, # 1, p. 55 - 56
