Carboxylates, phthalimides

By use of potassium phthalimide we can isolate the intermediate. a-Oxo-S-aminovaleric (9, = 1) and a-oxo-e-aminocaproic acids (9, = 2) readily yield 2l -pyrroline-2-carboxylic acid (10, =1) and. d -piperideine-2-carboxylic acids (10, n = 2), respectively (7-10). The equilibria of the acids with their cyclic forms was observed in water solutions (11,12). 

An isoindol1 none moiety forms part of the aromatic moiety of yet another antiinflammatory propionic acid derivative. Carboxylation of the anion from -nitro-ethylbenzene (45) leads directly to the propionic acid (46). Reduction of the nitro group followed by condensation of the resulting aniline (47) with phthalic anhydride affords the corresponding phthalimide (48). Treatment of that intermediate with zinc in acetic acid interestingly results in reduction of only one of the carbonyl groups to afford the isoindolone. There is thus obtained indoprofen (49). ... 

Esters of (V-hydroxyphthalimide can also be used for decarboxylation. Photolysis in the presence of an electron donor and a hydrogen atom donor leads to decarboxylation. Carboxyl radicals are formed by one-electron reduction of the phthalimide ring. 

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. 

There is normally a considerable difference in acidity of neighboring carboxyl groups due to the formation of one hydrogen bond between the groups. Stable ammonium salts are formed only by stronger acids. An imide, e.g., phthalimide, is formed when the ammonium salts are heated to higher temperatures. 

Protected primary allylic amines were generated from allylic carbonates and ammonia equivalents. Iridium-catalyzed allylic substitution has now been reported with sulfonamides [90, 91], imides [89, 91-93], and trifluoroacetamide [89] to form branched, protected, primary allylic amines (Table 5). When tested, yields and selectivities were highest from reactions catalyzed by complexes derived from L2. Reactions of potassium trifluoroacetamide and lithium di-tert-butyhminodi-carboxylate were conducted with catalysts derived from the simplified ligand L7. Reactions of nosylamide and trifluoroacetamide form singly-protected amine products. The other ammonia equivalents lead to the formation of doubly protected allylic amine products, but one protecting group can be removed selectively, except when the product is derived from phthalimide. 

An intermolecular addition on phthalimides employing heteroatom-substituted carboxylates was reported by the same group. In that study, a-thioalkyl-and a-oxoalkyl-substituted carboxylates were decarboxylated in the presence of... 

Guanidine forms salts with such relatively weak acids as nitromethane, phthalimide, phenol and carbonic acid [20], Interactions between carboxylate anions of proteins and added guanidinium ion are thought [19, 56] to be weaker than the interactions with ammonium ions the role of guanidinium-carboxylate interactions in stabilizing natural protein conformations has been discussed [36c]. A few reports of metal complex formation by guanidines [57-60], and aminoguanidines [61] have appeared. 

Carboxyl radicals are formed from one-electron reduction of the phthalimide ring. 

The expected synthesis of a-S-diaminovalerianic acid, which was attempted by Willstatter in 1900, by the action of ammonia upon a-B-dibromovalerianic acid, led to the synthesis of a-pyrrolidine-carboxylic acid, and only in the following year was the synthesis of this important naturally occurring diamino acid accomplished by E. Fischer. He made use of Gabriel s phthalimide method with a slight modification and obtained ornithine by the following series of reactions —... 

It was also synthesised by E. Fischer in 1901 from 7-phthalimido-propylmalonic ester which he employed in the preparation of ornithine. The bromine derivative of this compound when treated with ammonia gave a complex mixture of products which after hydrolysis by hydrochloric acid at 100° C. gave phthalimide and a-pyrrolidine carboxylic acid —... 

Hashimoto and co-workers (55) reported that generation of ylide 152 from aryl ester 151 in the presence of a chiral rhodium complex Rh2(S-PTTL)4, a chiral phthalimide substimted carboxylate, followed by cycloaddition with DMAD, led to the formation of adduct 153 in good yield and in 74% enantiomeric excess (ee). 

A new reagent, AMiydroxyphthalimide combined with Co(acac)n (n = 2,3), transforms alkylbenzenes to ketones, whereas methylbenzenes give the corresponding carboxylic acids.1121 Phthalimide N-oxyl was found to be the key intermediate. Novel oxoperoxo Mo(VI) complexes mediate the cost-effective and environmentally benign oxidation of methylbenzenes to carboxylic acids.1384 Similar green oxidation of p-xylene to terephthalic acid was reported by using a Ru-substituted heteropolyanion.1385... 

Aminomethyl)biphenyl-2-carboxylic acid (70) and -acetic acid (69) have been prepared from dibenzo-substituted oxepin-2-one 66 by potassium phthalimide ring opening. Further Arndt-Eistert homologation of 67 provided 68.[104]... 

Carboxylic acids react with aryl isocyanates, at elevated temperatures to yield anhydrides. The anhydrides subsequently evolve carbon dioxide to yield amines at elevated temperatures (70—72). The aromatic amines are further converted into amides by reaction with excess anhydride. Ortho diacids, such as phthalic acid [88-99-3], react with aryl isocyanates to yield the corresponding N-aryl phthalimides (73). Reactions with carboxylic acids are irreversible and commercially used to prepare polyamides and polyimides, two classes of high performance polymers for high temperature applications where chemical resistance is important. Base catalysis is recommended to reduce the formation of substituted urea by-products (74). 

In a typical run, the nitrile 1 (30 mmol) and phthalic acid 2 (36 mmol) were introduced into the reactor, and heated under stirring. In the kinetic studies, time zero is taken at complete dissolution of the phthalic acid. At the desired reaction time, the reactor was rapidly cooled in a water-ice mixture and then chloroform (30 mL) was added. The mixture was stirred for 5 min and then the solid was filtered off. The chloroform solution contains the unchanged nitrile 1, the amide and the carboxylic acid 3. The residual solid contains unchanged phthalic acid 2, phthalimide 4, and as the major component, phthalic anhydride 5. The volume of the chloroform solution was adjusted to 50 mL and naphthalene was added as an internal standard. The resulting solution was analyzed by GLC. 

Photoinduced electron transfer from the carboxylate ion to the excited triplet phthalimide (fcT = 293-300 kj mol-1) appears to be followed by a rapid protonation of the radical anion and cyclization via a biradical recombination reaction (Scheme 9.1). Acetone (which also acts as photosensitizer) containing a small amount of water is the solvent of choice, whereas potassium carbonate is the ideal base to enhance cyclization versus simple decarboxylation and ring opening of the phthalimide [4]. 

Sulfur can also act as an electron donor towards the phthalimide group competing with the carboxylate ion. Therefore, in bifunctional compounds incorporating the two electron donors (carboxylate and thioether groups), the connecting linker and the solvent is crucial for the result of the reaction (Scheme 9.6) [8],... 

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