Arenes, phthalimides

To a suspension of p-t-butyl calix[4]arene (15.44 mmol) in 200ml DMF was added NaH (123.52 mmol) and 320ml DMF, the mixture stirred 1 hour, and N-(3-bromopropyl)phthalimide (123.52 mmol) added. The mixture stirred 7 days at ambient temperature, 100 ml water added, and the resulting precipitate collected. The precipitate was dissolved in 200 ml chloroform, washed with 50 ml 15% HCl, dried, and the product isolated in 54% yield, mp = 213-215 °C. MS and H-NMR data supplied. 

Copper-mediated coupling reactions of / -iodocalixarenes with phthalimide followed by hydrazinolysis should be mentioned as an alternative and independent strategy to obtain p-aminocalixarenes . The carbazole-substituted derivatives 50 (Figure 8) were obtained similarly by Ulhnan coupling . CMPO derivatives (51c), urea compounds (51b), available also via the isocyanates (51a), may be mentioned additionally. Mono- (52) and diimides with acidic functions pointing towards the cavity, and the calix[6]arene-based acetylcholine esterase mimic (53) are more sophisticated examples. 

Photo-addition of alkenes to A methylnaphthalene dicarboxamides in benzene has been studied. The structure of the arene moiety in the imide was important in determining the reaction path. Mainly cyclobutane and oxetan formation occurred. The dicarboximide (342) undergoes photochemical cyclization with incorporation of methanol to yield the two products (343) and (344) in 55 and 16% respectively. This type of cyclization appears to be quite general for such systems and is also reported for the imides (345) and (346). A variety of products resulting from aminolysis, reduction, and radical coupling is produced on irradiation of the phthalimide (347) in diethylamine. ... 

The phthalimide functional group has absorption and ET properties which make it very attractive in terms of PET processes in which it is the oxidizing species. The application of phthalimide derivatives in carbon-carbon bond forming processes with electron-donating groups such as ethers, thioethers, amines, arenes, carboxylates, etc., has been reviewed. A PET decarboxylation-cycliz-ation sequence has been used for the synthesis of medium-sized (8-16) heterocyclic ring systems (15) from AT-phthaloylanthranilic amides coupled to ca-aminoacids (14). The same PET protocol has been used to convert di-, tri-, and tetrapeptides into cyclopeptides with a minimum of protection and activation... 

Photoadditions to phthalimides and related imides have again attracted much interest and it has been clearly shown that variation in the arene structure causes a change in the site of addition. Detailed studies of the photochemistry of N-methyl-9,10-phenanthrenedicarboximide (113) have been reported. Stereo-... 

The reactions between Y-(co-haloalkyl)phthalimides and sodium dialkyl phosphite were reported as early as 1949 by Chavane in the successful sytheses of several (co-aminoalkyl)phosphonic diesters. The advantage over the Michaelis-Arbuzov reaction in the preparation of (2-aminoethyl)phosphonic diesters with Y-alkyl or Y-silvl substituents is worth recalling, and several reports of its successful use may be noted, including the preparation of nitrogen-functionalized polyphosphonic esters (Scheme 17). Other substrates for the reaction have included l,3-bis(bromomethyl)benzene and 4-(co-bromoalkyl)arenes ... 

Our return to amination chemistry was inspired by the mechanistic studies of the Ullman reaction (Scheme 8). Hartwig had shown that the Cu(I)-phthalimide complex (38) could undergo oxidative addition with aryl halides to form a Cu(lll) intermediate (39), which then reductively eliminated to form a C—N bond (40). We hypothesized that a Cu(III)-phthalimide intermediate (42) could also be created by oxidation of 38 and a subsequent C—H metalation, presumably via a CMD mechanism (Scheme 8). Consequently, we synthesized 38 and reacted it with a series of oxidants and arenes in an attempt to discover a synthesis of protected anilines (e.g., 40) via C-H activation. The initial reactions were performed using stoichiometric amoimts of 38, but we intended to lower the catalyst loading once a lead reaction was discovered. 

In keeping with the seminal work of Kita, we proposed that the I(III)-mediated amination involved a radical cation intermediate that was generated by single electron transfer from the arene to the I(III) oxidant. The consequent radical cation should be highly reactive, and the attack of a phthalimide nucleophile would lead to a mixture of regiomeric products, like the 5 6 3 mixture that was observed for our toluene reaction (Scheme 10). This hypothesis contrasts with the mechanisms proposed by Chang and Antonchick, as electrophilic aromatic substitution, even with a reactive R2N species, should favor the para product. 

More general arenes and heteroarenes can be employed by the introduction of appropriate directing groups. Shen and coworkers reported the Cu0Ac/02-cata-lyzed C2-selective amination of lV-(2-pyrimidyl)indoles with phthalimide (Eq. 30) [56]. 

A synthesis of phthalimides via double carbonylative coupling of ortho-diiodo arenes with anilines has also been reported [98]. The conversion of 149 to 150 proceeded in good yield using a Pd/PPh3-based catalyst system (Eq. (1.59)). 

Reaction of iodonitrocalix[4]arenes with phthalimide in the presence of Cu(I)20 followed by treatment with hydrazine and cone. HCI provides an easy route into calix[4]arenes carrying both nitro and amino groups at the upper rim. In this way l,2-diiodo-3,4-dinitrocalix[4]arene 2b was converted to the corresponding aminonitro-calix[4]arene 4 in 58% yield. 

Stoichiometric intermolecular amination reactions of arenes have been explored to a larger extent recently. Of major interest had been the investigation on the behavior of phthalimide in the presence of hypervalent iodine as oxidation promoter, which was simultaneously reported by DeBoef and Chang (Scheme 6) [20, 21], The respective reactions of p-xylene 26 to 2-phthaloyl xylene 27 and arenes 28 to... 

In the palladium-catalysed reaction of phthalimides with mono-, di-, and tri-substituted arenes lacking a DG, it has been shown that steric effects were dominant with ort/io-aminated products being disfavoured.The reaction of arenes with N-tosyloxytrichloroethyl carbamates is catalysed by copper with a neocuproine ligand and yields amidated derivatives. Reaction is faster with electron-rich arenes and the kinetic isotope effect, value of 0.9. The suggested mechanism involves... 

Among the nucleophiles which can be introduced by this reaction are carboxylate ions, ° phthalimide anions,alkoxide ions, and acetylide groups.In many of these reactions there is competitive reduction of the aryl halide to the arene. 

Another typical example for the direct oxidative transformation of methyl arenes were developed by Wang and co-workers [118]. In this palladium catalyzed reaction, tert-butyl nitrite (TBN) was employed as both nitrogen source and oxidant N-hydroxyphthalimide (NHPI) was used as precursor of the active phthalimide N-oxyl (PINO) radical, which initiates the reaction to give benzylic radical A by grabbing hydrogen atom from the substrate. In the interaction between TBN and NHPI, TBN decomposes to NO radical and tert-butyl alcohol. NO radical would trap benzylic radical A to give nitrosomethyl benzene B, which isomerizes to aldoxime C [119]. Finally, nitrile product would be generated fitom C by palladium catalysis (Scheme 4.21). 

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