Phthalimide radical

The transformation of isoquinoline has been studied both under photochemical conditions with hydrogen peroxide, and in the dark with hydroxyl radicals (Beitz et al. 1998). The former resulted in fission of the pyridine ring with the formation of phthalic dialdehyde and phthalimide, whereas the major product from the latter reaction involved oxidation of the benzene ring with formation of the isoquinoline-5,8-quinone and a hydroxylated quinone. 

Photolysis of a variety of substances including hydrogen peroxide, phthalimide hydroperoxides (104), N-hydroxypyridinethiones (105), pyrimido[5,4-g]pteridinetetrone N-oxides (106), and N-arylalkyl-Af-phenylhydroxylamines (107) has been reported to generate hydroxyl radical in aqueous solutions. ... 

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. 

Catalysis by nitroxyl radicals in hydrocarbon oxidation was discovered and studied recently [82-89], The introduction of /V-hydroxyphthalimide into oxidized alkylaromatic hydrocarbon was found to accelerate the oxidation. The formation of the stable phthalimide-/V-oxyl (PINO) radical was evidenced by the EPR method [90]. The following kinetic scheme was put forward to explain the accelerating effect of PINO on the chain oxidation of hydrocarbons [82-84]. 

The photochemistry of imides, especially of the N-substituted phthalimides, has been studied intensively by several research groups during the last two decades [233-235]. It has been shown that the determining step in inter- and intramolecular photoreactions of phthalimides with various electron donors is the electron transfer process. In terms of a rapid proton transfer from the intermediate radical cation to the phthalimide moieties the photocyclization can also be rationalized via a charge transfer complex in the excited state. 

To discern the ion-radical nature of reactions, the so-called intramolecular and intermolecular proton/deuterium isotope effects may be of use. Baciocchi et al. (2005) revealed ion-radical mechanism for A-demethylation of A,A-dimethylanilines, (CH3)2NAr, by phthalimide-A-oxyl radical (Scheme 4.14). In this reaction, ( e/ D)intra values were derived for reactivity of (CD3)(CH3)NAr, whereas ( H/ D)inter was referred for the reactivity of (CD3)2NAr. The values of (A e/ D)intra were found to be always different and higher than These results, although are incompat-... 

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

The radical C-H transformation of ethers is generally initiated by a-hydrogen abstraction with highly reactive radicals generated from such initiators as peroxides [3a, g], photo-activated carbonyl compounds [3b—d], metallic reagents [3i, j], and redox systems [3f, h[. Various combinations of ethers, radical initiators, and radical acceptors (e.g. carbon-carbon multiple bonds) may be used as the reaction components [6], Several notable means of direct C-C bond formation via the radical a-C-H transformation of ethers involve the use of triflon derivatives [7], the phthalimide-N-oxyl (PINO) radical [8], 2-chloroethylsulfonyl oxime ethers [9], and N-acyl aldohydrazones [10],... 

The mechanism of the aerobic oxidation of alcohols depends on the particular catalyst used. Two general mechanisms can be considered (1) the direct oxygenation of alcohols by 02 through a free-radical chain process initiated by the catalyst, and (2) the direct oxidation of the alcohol by the catalyst, which is then regenerated by 02. Both mechanisms are well illustrated [6] by the aerobic oxidations catalyzed by the persistent tetramethylpiperidine-N-oxyl (TEMPO) radical 1 and the nonpersis-tent phthalimide-N-oxyl (PINO) radical 2. 

Finally, as examples of similar types of reactions, photolytic treatment of O-acyl ester (D) of benzophenone oxime, A-acyloxy-phthalimide (E), and O-acyl ester (F) of A-hydroxy-2-pyridone with a mercury lamp generates the corresponding alkyl radicals via decarboxylation. However, these reactions can be used only for the alkylation of aromatics (solvents such as benzene) and reduction [86-89], so their synthetic utility is extremely limited. 

A PET reaction between excess phthalimide (in equilibrium with its conjugate base) and an alkene led to a clean phthalimidation of nonactivated double bonds. Here, the singlet excited state of phthalimide acts as the oxidant and a radical ion pair is formed. The olefin cation radical is trapped by the phthalimide anion, and back electron transfer, followed by protonation, affords the photoaddition products [40], Protected phenethylamines are readily accessible in this way. This reaction has been carried out by using NaOH as the base it has been shown that the amounts (usually equimolar with the alkene) must be carefully chosen in order to avoid the undesired competition with [2 + 2] photocycloaddition. 

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]. 

N-Phthalimide-linked peptides that contain C-terminal a-amidotrimethylsilyl groups undergo macrocyclization reactions via sequential single-electron transfer processes [11, 12]. Thus, electron transfer from the neighboring amide to the excited phthalimide chromophore leads to an amide radical cation. Hole migration to the ot-amidotrimethylsilane center is followed by desilylation to form an 1, co-biradical intermediate, which finally cydizes to the macrocydic peptide (Scheme 9.9). 

There were relatively few examples reported, in which the chromo-phoric group was an aryl ketone (Ilia) whereas much more PET induced cyclizations with phthalimides (Illb) are known, sometimes other imides, such as succinimides and maleimides were also used. Phthalimides differ from aryl ketones in some respects despite their apparently similar photophysical properties. On one hand, their reduction potential is remarkably lower in comparison with aryl ketones [13]. On the other hand, the radical anion derived from phthalimides is clearly more stable than the corresponding species from aryl ketones [15]. Both facts increase the thermodynamic driving force of a PET and facilitates applications that are unknown from aryl ketones. In this context, one of the most successful approaches is a PET-induced decarboxylation-cyclization route, developed by Griesbeck [13]. The details of this interesting method will be discussed in Sec. 3.4.6. 

However, the reduction potential of pthalimides is remarkably lower compared with aromatic ketones (e.g., V-methylphtalimide in DMF ed =— 1.37Y [25a], valerophenone ed =— 2.07 Y [30]). The radicals A and the radical anions B formed by hydrogen or electron transfer onto the triplet excited phthalimide are more stable than the corresponding species derived from aryl ketones (C and D), even though the triplet energies are very close (A is more stable than C by about 29 kJ/mol, Sch. 5) [31]. 

This stabilization of the radical intermediates, arising from a better mesomeric stabilization of radicals in the phthalimide moiety, consequently increase the exoenergicity of reactions and, according to the Bell-Evans-Polanyi principle, lowers the activation barrier and thus enables processes that are unknown from ketones. The unique photochemical reactivity of phthalimides will be demonstrated with some examples. 

The progress of intramolecular PET-reactions involving alkenyl phthalimides in essentially influenced by the solvent [29]. Upon irradiation in MeCN, [n2 + a2]-addition to the C(0)-N bond takes place and benzazepinediones are obtained. In alcohol, the intermediary formed radical cation is trapped in an aw/z -Markovnikov fashion depending on the polarity as well as the nucleophilicity of the solvent [30]. Recently, Xue et al. described an interesting modification of the latter process using tetrachloro-phthalimides with remote hydroxy alkyl substituents (13) [31]. During... 

Phthalimides have often been used in the double role of electron acceptor sensitizers and radical traps, and are in fact benzylated by irradiation in the presence of toluene and several other precursors. 4,5-Dicyanophthalimide undergoes substitution of a benzyl for a cyano group when irradiated with toluene, but mainly attack at the imide carbon occurs with diphenylmethane. With various donors the competition between the two modes of reaction has been found to depend on the cage vs. out of cage radical cation cleavage, in the first case with the assistance of the radical anion [223] (Sch. 18). 

Cross-linked poly(vinyl-amine) was obtained by hydrazinolysis of a cross-linked poly(N-vinylphthalimide), in turn obtained by radical copolymerization of N-vinyl-phthalimide and divinylbenzene 6). 

Okada, Okamoto and Oda [97] have recently described a novel method of decarboxylation through a PET bond cleavage process in IV-acyloxyphthalimides. A photoexcited electron donor such as l,6-bis(dimethylamino)pyrene (BDMAP) transfers an electron to the phthalimide to produce an anion-radical that is protonated to form a radical prior to homolytic N—O bond cleavage. Bond... 

Related photochemistry has also been examined with other functional groups such as phthalimides, which also abstract nearby hydrogens with the photoexcited carbonyl group. - Furthermore, since the hydrogen abstraction is performed by the half-vacant nonbonding orbital of a photoexcited ketone carbonyl, related chemistry is observed if the electron is removed electrochemically, not just photoexcited into a Tr -orbital. Electrochemical functionalization of nearby carbons has been reported in which, after hydrogen atom abstraction by an oxidized ketone, the resulting radical is electrochemically oxidized further to the carbon cation, which reacts with solvent (Scheme 7). ... 

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