4-Nitrophthalic anhydride reaction

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°. 

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. 

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,... 

Phthalic anhydrides readily form hydrogen phthalate esters on reaction with alcohols the derivatives from 3-nitrophthalic anhydride are usually nicely crystalline compounds and are hence suitable for purposes of characterisation. Hydrogen phthalate esters are also useful in appropriate instances for the resolution of racemic alcohols (Section 5.19). 

Heat 0.5 g (or 0.5 ml) of the amine with 0.5 g of pure 3-nitrophthalic anhydride (Expt 6.162) in an oil bath at 145-150 °C for 10-20 minutes, pour the reaction mixture into a small mortar or Pyrex dish and allow it to solidify. Recrystallise from ethanol, aqueous ethanol or ethanol-acetone. 

Mix 3-nitrophthalic anhydride (0.005 mol or 1.0 g) and the thiol (0.0075 mol, or 1.0 g if the molecular weight it not known) in a test tube and heat gently over a free flame for about 30 seconds. Allow the mixture to cool, and add 0.5 ml of 2 m sodium hydroxide solution dropwise and with cooling in an ice bath. Then add about 0.3 ml of 2 m hydrochloric acid and shake the reaction mixture vigorously. Collect the solid which separates by suction filtration and dry it upon a porous tile. Recrystallise from dilute acetic acid or from aqueous acetone. 

For polyimides to be useful polymers, they must be processable, which means that they have to be meltable. Melt processability of polyimides can be improved by combining the basic imide structure with more flexible aromatic groups. This can be achieved by the use of diamines that can introduce flexible linkages like aromatic ethers and amides into the backbone. Polyamide-imides (5) are obtained by condensing trimellitio anhydrides and aromatic diamines, while polyetherimides (6) are produced by nitro displacement reaction involving bisphenol A, 4,4 -methylenedianiline, and 3-nitrophthalic anhydride. 

The thermoplastic variety of polyimides with enhanced melt processabihty is obtained by combining the basic imide stmcture with more flexible aromatic groups such as aromatic ethers or amides. Polyamide-imides are produced by condensing trimellitic anhydrides with aromatic diamines, while polyetherimides are made by the reaction between bisphenol A, 4,4 -methylene dianiline, and 3-nitrophthalic anhydride. 

The first step of this synthesis is to form a bis-imide monomer formed by the reaction of nitrophthalic anhydride and a diamine (see Figure 4.21). The second step of polyetherimide synthesis involves the formation of a bisphenol dianion by treatment of a diphenol with two equivalents of base, followed by... 

Today we routinely use the 3-nitrophthalic anhydride blocker It is applicated in a single dose of a ten- to twenty fold excess on estimated amounts of remaining amino functions and added as a 0.1 niolar solution in pure pyridine with ten minutes reaction time at the end of each peptide synthesis stage, in which all chemical operations are monitored by photometric control and forced to approach completion. We have no indications to date that the acidically marked, blocked sequences on polymer cause undesired side reactions in subsequent stages of the synthesis, particularly in further peptide coupUngs, probably because of the acidity of the blocker functions (pK 2), which in their anionic salt form possess only a very diminished nucleophilicity. 

Two diphenylaminophthalides have been synthesized The 3,3-diphenyl-6-aminophthalide [24] was synthesized in 20% yield by the following sequence of reactions which was patterned after early work °. This series involved nitration of phthalimide, hydrolysis and dehydration to 4-nitrophthalic anhydride, Friedel-Crafts reaction with benzene to 2-benzoyl-5-nitrobenzoic acid, cyclization with thionyl chloride to the pseudoacid chloride, Friedel-Crafts reactions with benzene, and, finally reduction of the nitro group to the amino function with Adams catalyst. 

While 3-nitrophthalic anhydride is more suitable for the identification of larger quantities of alcohols (over 20 mg), tetrachlorophthalic anhydride was used for the identification of tertiary alcohols after their reaction with Grignard reagent (16). 

Among chemical methods for the separation of amines, those of Hinsberg (reaction with / -toluenesulfonyl chloride) and of Alexander (94) (reaction with 3-nitrophthalic anhydride) are most commonly used. Tertiary amines do not react with the reagents mentioned and they can be separated after the reaction — for example, by extraction. Derivatives of primary amines with p-toluenesulfonyl chloride are soluble in alkali hydroxide solutions, in contrast to sulfonamides of secondary amines this is utilized for their separation. When primary and secondary amines are separated by reacting them with 3-nitrophthalic anhydride, use is made of the fact that only phthal-imine acids derived from primary amines can be cyclized. Practical utilization of both procedures is demonstrated by the separated of a mixture of aniline, ethylaniline, and diethylaniline. However, it should be mentioned that in a number of cases the procedures fail or do not lead to a sufficiently sharp separation. Negatively substituted amines which do not react with / -toluenesulfonyl chloride can be separated with 3-nitrophthalic anhydride. Some p-toluenesulfonamides of primary amines are poorly soluble in alkali. The derivative of primary amine with 3-nitrophthalic anhydride is cyclized merely by boiling in benzene, and the phthalimide formed is soluble in benzene and can be isolated together with the tertiary amine. 

Several thioureas have been synthesized by ring-opening reactions of heterocyclic compounds such as l,3-dithiolan-2-thiones, 5-arylimino-l,2,4-dithiazolidine-3-thiones, benzoxazole-2-thiones, and 3,1-benzo-thiazine-4-thione derivatives. Similarly, the action of triphenylphosphine on 5-amino-l,2,4-dithiazolo-3-thiones gave thiocarbamoyl isothiocyanates (304). Other thioureas have been obtained by thermolytic decarbonylation of 2-amino-5(4H)-thiazolones and by treatment of 4,5,6,7-tetrahydro-cyclopenta-l,3-dioxin-4-one" and 3-nitrophthalic anhydride with thiourea. ... 

More commonly, but incorrectly, named thiophthalic anhydride and sometimes referred to as phthaloyl monosulfide or o-phthalyl sulfide, this compound (104) may be prepared by heating phthalic anhydride with sodium sulfide125 or by heating phthaloyl chloride with potassium hydrogen sulfide,126 hydrogen sulfide,127 or ethanolic sodium disulfide.128 The reaction between phthaloyl chloride and hydrogen sulfide also gives phthalic anhydride and di-o-phthaloyl disulfide.127 Early attempts to prepare 104 have been described by Chakravarti.126 4-Nitrophthalic thioanhydride may be prepared by hydrolysis of 8 (R = N02 X = C1) (Section III, A).22... 

Reaction of 4,5-dimethyl-tetrahydrophthalic anhydride with methyl dithiocarbazate results in formation of hydrazide (110), which is cyclized in hot sulfuric acid to the 5,2,3-benzothiadiazocin-1,6-dione (111), as shown in Scheme 18 <88MI 925-0i>. Similar cyclizations are reported to occur using 3-nitrophthalic <87MI 925-01 > and quinolinic anhydrides <87MI 925-02>. 

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