Phthalimide conversion

Imides (e.g. phthalimide) can be purified by conversion to their potassium salts by reaction in ethanol with ethanolic potassium hydroxide. Hie imides are regenerated when the salts are hydrolysed with dilute acid. Like amides, imides readily crystallise from alcohols and, in some cases (e.g. quinolinic imide), from glacial acetic acid. 

Phthalic anhydride derivatives are also not typical precursors in phthalocyanine formation. Their use is of interest in cases where the substituents prohibit conversion of the anhydride to nitrogen-containing derivatives like phthalimides or phthalonitriles. 

Phenothiazines are well-known as intermediates for pharmaceuticals, and are also active as insecticides and antioxidants. These compounds are usually prepared by the thiation of diphenylamines with elemental sulfur. In this context, the group of Toma has elaborated a synthesis of 3-phthalimidophenothiazine, as shown in Scheme 6.265 [455]. Using a variety of high-boiling solvents under conventional thermal reflux conditions, low isolated yields of the desired product were obtained. The highest conversion and isolated product yield (55%) was achieved by microwave irradiation of a mixture of the starting N-(4-phenylaminophenyl)phthalimide with... 

For the cydative cleavage step, it turned out that aprotic conditions were definitely superior to the use of protic media. Thus, employing N,N-dimethylformamide as solvent at somewhat elevated temperatures furnished the desired compounds in high yields and excellent purities. Having established the optimized conditions, various phthalic acids and amines were employed to prepare a set of phthalimides (Scheme 7.51). However, the nature of the amine was seen to have an effect on the outcome of the reaction. Benzyl derivatives furnished somewhat lower yields, probably due to the reduced activities of these amines. Aromatic amines could not be included in the study as auto-induced ring-closure occurred during the conversion of the polymer-bound phthalic acid. 

The thioimides can be hydrolyzed to the corresponding di-carboxylic acids. The thioimides can be converted to the corresponding imides, and thiohomophthalimides can be converted to phthalimides both conversions are one-step processes.4 Thus a variety of substituted phthalic and homophthalic acids and their derivatives are available from these thioimides. 

Scheme 33 Conversion of a carbohydrate-based N-alkoxy phthalimide to a spirocyclic acetal...

By selection of an appropriate derivative the hydroxyl group can become activated towards displacement (via an 8 2 exchange process) with a suitably chosen nucleophile. Conversion to the sulfonate ester (SO2R) [115] promotes displacement by either an acetate ( OAc) (sequence Dl) or phthalimide nucleophile (Sequence D2), whilst the trimethylsilyl derivative facilitates introduction of fluorine (Sequence E) [116]. 

A detailed study of the conversion of 3,4-dichloro-l,2,5-thiadiazole into 3,4-diamino-l,2,5-thia-diazole has been carried out <76JHC13>. Reaction with lithium or sodium amide produces only 4% of the diamine together with cyano-containing by-products, a consequence of direct attack on sulfur. Use of a less powerful nucleophile, ammonia or potassium phthalimide, resulted in an increased attack on carbon and produced the diamine in 24% and 66% yields, respectively. Secondary amines, e.g. morpholine <76JOC3l2l> and dimethylamine <72JMC315>, produce the normal displacement products. The reaction of dichlorothiadiazole with potassium fluoride in sulfolane gives a mixture of 3-chloro-4-fluoro and 3,4-difluoro-l,2,5-thiadiazole <82CB2135>. 

Use ester rather than acid to prevent conversion of anion to phthalimide. 

Bromine trifluoride has found application in the conversion of (methylsulfanyl)thiocar-bonyl groups, bonded to carbon atoms in aromatic rings, oxygen atoms in alcohols and phenols, or to the phthalimide nitrogen atom, into trifluoromethyl groups.125... 

The sulfenyl phthalimides are one of the oldest groups of fungicides and are effective, safe and persistent (B-77MI10706). Captan (59) is cheaply made from the Diels-Alder adduct of butadiene and maleic anhydride, followed by conversion to the imide and reaction with trichloromethanesulfenyl chloride. Folpet (60) and captafol (61) are similar in structure. 

Despite the expenditure of a tremendous amount of effort throughout the world, the two original methods employed in the manufacture of copper phthalocyanine are still used. In the first, a mixture of phthalic anhydride, urea and copper(I) chloride is heated in a high-boiling solvent such as nitrobenzene or trichlorobenzene in the presence of a catalytic amount of ammonium molybdate. The crude copper phthalocyanine is filtered off and the solvent recovered by distillation. The urea acts as a source of nitrogen and the first step in the overall reaction (equation 18) is conversion of phthalic anhydride to phthalimide (219) by ammonia liberated by the urea. More ammonia then converts the phthalimide to l-keto-3-iminoisoindoline (220) and finally to l-amino-3-iminoisoin-dolenine (221). All three intermediates have been isolated and identified. In the presence of copper chloride the l-amino-3-iminoisoindolenine undergoes conversion to the copper complex of phthalocyanine. 

Explicitly included are species with carbonyl (>CO) groups such as the isomeric phthalimide (VIII) and isatin (IX), and with thiocarbonyl (>CS) groups such as the isomeric benzo-l,2-dithol-3-thione (X) and benzo-l,3-dithiol-2-thione (phenylene trithiocarbonate) (XI). Conversely, species with the isoelectronic >BF (and the related >BH) are ignored. Thus the question of the aromaticity in carboranes never arises in this chapter, even had we been explicitly interested in three-dimensional aromaticity (another issue we will ignore here). 

Photoinduced electron transfer reactions of aminoalkyl-substituted phthalimides are highly exergonic, but since amines are potent hydrogen donors, photoreductions are commonly observed side-reactions. The product spectrum parallels that of the thioether case (vide supra) although yields were in general lower [28]. Higher conversions and yields up to 39% were obtained for dibenzylated amines [28c]. 

Selenenamides (23) are obtained by the substitution of selenenyl halides with amines or by the metathesis of the former compounds with Af-silylamines. N-(Phenylseleno)phthalimide (24) is similarly obtained using potassium phthalimide (Scheme 10). These compounds can be isolated but are prone to hydrolyze when exposed to moisture. Selenenamides react with aldehydes or jS-dicarbonyl compounds to afford a-seleno derivatives (as in the process shown in equation 11), and add to activated double and triple bonds, as in the example in equation (19). The imide (24) is a useful alternative to PhSeCl in various selenenylation reactions, and to ArSeCN in the conversion of alcohols and carboxylic acids to selenides and selenoesters (8), as shown in Scheme 3. 

Scheme 20.3 Reaction network in o-xylene conversion to phthalimide and phthalonitrile. Adapted from [84].

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