Nitrophthalic anhydride

The nitration of phthalic anhydride with a mixture of concentrated sulphuric and nitric acids yields a mixture of 3-nitro- and 4 nitro phthalic acids these are readily separated by taking advantage of the greater solubility of the 4 nitro acid in water. Treatment of 3 nitrophtlialic acid with acetic anhydride gives 3 nitrophthahe anhydride. 

3-Nitrophthalic acid. Equip a 1500 ml. three-necked flask, supported on a water or steam bath, with a dropping funnel, a mechanical stirrer and a thermometer the neck through which the stirrer passes should be open and the stirrer should be cormected by means of a belt to the motor (nitrous fumes are evolved in the subsequent reaction and these would damage the motor if supported directly over the reaction 

Submitted by B. H. Nicolet and J. A. Bender. Checked by Frank C. Whitmore and W. F. Sincleton. 

3-Nitrophlhalic anhydride has been prepared by heating the acid under various conditions1 and by the action of acetic anhydride,2 essentially as in the present method. 

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Hydrogen 3-nitrophthalates. 3-Nitrophthalic anhydride, a yellow crystaUine powder of m.p. 163-164°, reacts with alcohols to yield esters of 3-nitrophthalic acid ... 

For alcohols of b.p. below 150°, mix 0- 5 g. of 3-nitrophthalic anhydride (Section VII,19) and 0-5 ml. (0-4 g.) of the dry alcohol in a test-tube fitted with a short condenser, and heat under reflux for 10 minutes after the mixture liquefies. For alcohols boiling above 150°, use the same quantities of reactants, add 5 ml. of dry toluene, heat under reflux until all the anhydride has dissolved and then for 20 minutes more remove the toluene under reduced pressure (suction with water pump). The reaction product usually solidifies upon cooling, particularly upon rubbing with a glass rod and standing. If it does not crystallise, extract it with dilute sodium bicarbonate solution, wash the extract with ether, and acidify. Recrystallise from hot water, or from 30 to 40 per cent, ethanol or from toluene. It may be noted that the m.p. of 3-nitrophthalic acid is 218°. 

Experimental details for the preparation of derivatives with benzoyl chloride and with 3-nitrophthalic anhydride are given in Section IV,100,2 and 7. 

Derivatives with 3-nitrophthalic anhydride. 3-Nitrophthalic anhydride reacts with primary and secondary amines to yield nitro-phthalamic acids it does not react with tertiary amines. The phthalamic acid derived from a primary amine undergoes dehydration when heated to 145° to give a neutral A -substituted 3-nitrophthalimide. The phthalamic acid from a secondary amine is stable to heat and is, of course, soluble in alkali. The reagent therefore provides a method for distinguishing and separating a mixture of primary and secondary amines. 

Other derivatives can be prepared by reaction of the alcohol with an acid anhydride. For example, phthalic or 3-nitrophthalic anhydride (I mol) and the alcohol (Imol) are refluxed for half to one hour in a non-hydroxylic solvent, e.g. toluene or alcohol-free chloroform, and then cooled. The phthalate ester crystallises out, is precipitated by the addition of low boiling petroleum ether or is isolated by ev toration of the solvent. It is recrystallised from water, 50% aqueous ethanol, toluene or low boiling petroleum ether. Such an ester has a characteristic melting point and the alcohol can be recovered by acid or alkaline hydrolysis. 

Nitrophthalic anhydride [641-70-3] M 193.1, m 164 . Crystd from benzene, benzene/pet ether, acetic actic or acetone. Dried at 100°. 

Potassium nitrite by-product can react with nitroaromatic substrate to suppress yields of aryl fluorides Modest yields (40-60%) of fluorophthafic anhydride are obtained from 3- or 4-nitiophthalic anhydride and potassium fluonde due to formation of by-product dipotassium salt of 3- or 4-nitrophtlialic acid [1/3,114, 115] (equation 33) Higher yields (93%) of 3-fluorophfhalic anhydride can be realized by regenera tion of 3-nitrophthalic anhydride from the dipotassium salt with thionyl chloride, followed by addition of fresh potassium fluoride [7/5] (equation 33)... 

Heat 3-nitrophthalic anhydride with ammonium carbonate to get 3-nitrophthalimide (I). Dissolve 4.3 g (I) in 50 ml 90% methanol and add 1.9 g sodium borohydride over 30 minutes while stirring vigorously at room temperature. Stir 2 hours, acidify with 20% HCI, evaporate in vacuum and treat the dry residue with acetone. Evaporate in vacuum to get 3.9 g (88%) 3-OH-4-nitrophthal-imidine (II) (recrystallize from acetone). Dissolve 3.9 g (II) in 40 ml 20% HCI and stir for 10 hours on water bath at 80-90°. Distill off HCI and stir residue with acetone. Filter and evaporate in vacuum to get 3.4 g 3-OH-4-nitrophthalide (III) (recrystallize from CHC 3 and can purify on column). Prepare an ether solution of CH2N2 and add to 1.93 g (III) in a 100 ml flask until a reaction is no longer evident. Add acetic acid to decompose excess diazomethane and evaporate in vacuum to get about 2 g of 2-methoxycarbonyl-6-nitrostyrene oxide (IV) (can purify on column). Dissolve 560 mg (IV) in 50 ml absolute methanol, add 50 mg Pt02 and hydrogenate as described elsewhere here (other reducing methods should work). Filter,... 

T Wieland, C Birr, H Wissenbach. 3-Nitrophthalic anhydride as blocking agent in Merrifield polypeptide synthesis. Angew Chem 8, 764, 1969. 

The high reactivity of 3-nitrophthalic anhydride (at C-l carbonyl) towards amines [143] may be ascribed to the influence of the nitro group through polarity alternation. 

For phthalic anhydride based compound, no isomeric forms possible. For 3-nitrophthalic anhydride, only isomer II formed. 

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