Isoindolines, formation

As expected, addition of IV tended to increase the sol fraction in the cured specimens. The statistical theory of gelation (9) can be used to calculate the expected gel fraction as a function of crosslink functionality, extent of reaction, and proportion of difunctional units in the mixture. For these mixtures, an adequate fit to the extraction data was obtained by assuming that the primary reaction is isoindoline formation (Figure 5). Triazine or phthalocyanine formation alone cannot account for the data. 

Pyrolytic elimination from isoindoline A -oxides also affords iso-indoles, but yields were found to be generally lower than those obtained by Kreher and Seubert s procedure. The considerable amount of polymeric material formed in the pyrolytic reaction makes isolation of the isoindole difficult, but a convenient method for separation of the product was found utilizing complex formation with 1,3,5 -trin i tro benzene. 

Nevertheless, the adjacent position of the amide and acetylenic groups was used in another type of heterocyclization. The nitrogen atom in the amide group is a weak nucleophile. Therefore, the N anion should be generated by potassium ethoxide. There are two possible variants of nucleophilic addition to the triple bond. Only one takes place, i.e., the formation of y-lactam. After 7 h of heating in EtOH in the presence of KOH, amide 72 isomerized into the known isoindoline 73 in 80% yield (Scheme 128). 

In contrast to phthalocyanines (tetra- or octasubstituted) in which the isoindoline units carry all the same substituents, reports of phthalocyanines with lower symmetry, which have been prepared by using two different phthalonitriles, have rarely appeared. This is due to the problems which are associated with their preparation and separation. For the preparation of unsymmetrical phthalocyanines with two different isoindoline units four methods are known the polymer support route,300 " 303 via enlargement of subphthalocyanines,304 " 308 via reaction ofl,3,3-trichloroisoindoline and isoindolinediimine309,310 and the statistical condensation followed by a separation of the products.111,311 319 Using the first two methods, only one product, formed by three identical and one other isoindoline unit, should be produced. The third method can be used to prepare a linear product with D2h symmetry formed by two identical isoindoline units. For the synthesis of the other type of unsymmetrical phthalocyanine the method of statistical condensation must be chosen. In such a condensation of two phthalonitriles the formation of six different phthalocyanines320 is possible. 

The reaction is initiated by attack of a nucleophile (Ye), usually the counterion associated with the Cu ion, at one of the CN groups of the phthalonitrile, which is activated by its coordination with the Cu ion. Subsequently a cycliza-tion reaction to an isoindoline derivative takes place. These steps are three times repeated by a series of similar reactions finally resulting in a cyclization to a CuPc ring intermediate, whose formation is facilitated by the coordinating role of the copper ion. With a copper (II) salt as reactant it is suggested that Y is eliminated from the intermediate, e.g. the Cl ion in the case of CuCl2. The monochloro de-rivate of CuPc is than formed by an electrophilic attack of Cl on the CuPc initially formed. 

In the same year, Enders and coworkers reported an asymmetric one-pot, two-step synthesis of substituted isoindolines 159 in the presence of chiral A-triflyl phosphoramide (R)-Ae (10 mol%, R = d-NO -C H ) (Scheme 67) [87]. The cascade was triggered by a Brpnsted acid-catalyzed aza-Friedel-Crafts reaction of indoles 29 and A-tosyliminoenoates 160 followed by a DBU-mediated aza-Michael cyclization of intermediates 161 to afford the isoindolines 159 in high yields (71-99%) and short reaction times (10 min to 4 h) along with good enantioselectivities (52-90% ee). Longer reaction times (16 h to 10 days) caused increasing formation of the bisindole byproduct 162 (Scheme 68) along with amplified optical purity of isoindolines 159. 

In the presence of trace amounts of water, the tetrameric p,2-oxo complex (182) in 1,2-dimethoxyethane is transformed into a p, -oxo tetrameric complex (183 equation 254), characterized by an X-ray structure.574 In contrast, (182) 572,575 is inactive towards the oxidation of phenols. The reaction of N,N,N, AT -tetramethyl-l,3-propanediamine (TMP) with CuCl, C02 and dioxygen results in the quantitative formation of the /z-carbonato complex (184 equation 255).s76 This compound acts as an initiator for the oxidative coupling of phenols by 02. 6 Such jz-carbonato complexes, also prepared from the reaction of Cu(BPI)CO with 02 [BPI = 1,3 bis(2-(4-methyl-pyridyl)imino)isoindoline],577 are presumably involved as reactive intermediates in the oxidative carbonylation of methanol to dimethyl carbonate (see below).578 Upon reaction with methanol, the tetrameric complex (182 L = Py X = Cl) produces the bis(/z-methoxo) complex (185 equation 256), which has been characterized by an X-ray structure,579 and is reactive for the oxidatiye cleavage of pyrocatechol to muconic acid derivatives.580,581... 

Ebden, M. R. Simpkins, N. S. Fox, D. N. A. Activation of benzylic amines towards regioselective metalation by borane complex formation. Tetrahedron Lett. 1995, 36, 8697—8700. Ariffin, A. Blake, A. J. Ebden, M. R. H, W.-S. Simpkins, N. S. Fox, D. N. A. The diastereose-lective and enantioselective substitution reactions of an isoindoline-borane complex. 

Hydrogenation of phthalonitrile over Raney Ni does not give the corresponding diamine, but isoindoline in 91-98% yields due to extensive occurrence of cyclization (eq. 7.59).110 Likewise, hydrogenation of succinonitrile and glutaronitrile leads to the formation of pyrrolidines and piperidines, respectively. 

Although the precise mechanism of formation of phthalocyanines is unknown, it is generally thought that isoindoline intermediates are involved. A notional cyclization process could be that shown in equation (43). Template synthesis of phthalocyanines can also be achieved starting with 1,3-diiminoisoindoline and various analogs can be obtained from combinations of starting materials. Ligands such as (96) and (97) can be synthesized in this manner. 

Isoindoline derivatives, formation by cyclization of quaternary ammonium salts 79AKZ596. 

Since the polymerization of these bis-phthalonitriles were carried out without benefit of those conditions which are known to promote phthalocyanine ring formation, some question exists as to the chemical nature of these materials. In addition to the phthalocyanine ring, isoindoline (III) or triazine (IV) structures are also possible. Structure III is well known and, in-... 

Cyclotetramerization of eight cyano functions must be accompanied with transfer of two additional electrons in order to give a phthalocyanine. If the co-reactant is not able to undergo ready oxidation, then alternate products such as triazene or linear isoindoline would be the expected products since their formation does not require a redox reaction to occur. 

Conditions for the formation of isoindoles by the reduction of phthal-imides have proved difficult to establish. Reduction of phthalimide itself with lithium aluminum hydride gives isoindoline. However, Garmaise and Ryan54 have shown that N-benzylphthalimide can be reduced with a modified hydride reductant [sodium bis(2-methoxyethoxy)aluminum hydride] to give 2-benzylisoindole in moderate yield under mild conditions. 

IIA6B17 by screening a library built around a formation assays. See Fig. 9.1-9 for peptidomimetic isoindoline scaffold [52]. A biological data. 

Isoindolines and isoquinolines a,co-Diynes in which the connecting chains contain a nitrogen atom undergo [2+2+2]-cycloaddition with ketene equivalents derived from the carbene complexes. After the formation of a benzene ring, the products are isoindoline or isoquinoline derivatives. 

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