Isoindoline structure

An interesting sulfonamide diuretic that has little resemblance structurally to the thiazides is chlorthalidone, a benzophenone derivative. On a dose basis, it has an activity comparable to hydrochlorothiazide but is a much stronger carbonic anhydrase inhibitor than the thiazides, approximately 40 times sulfanilamide. Physical data indicate this compound to have the isoindoline structure rather than the benzophenone structure, I. The outstanding feature of this drug is its long duration of action, up to 72 hours (22, 32, 66). 

Teitel et al. prepared tetracyclic benzazepineisoindole, i.e., Schopf s base VI (104a), from /3-hydrastine (100, 675). This base is a convenient intermediate for further chemical transformation into the protopine skeleton Hofmann degradation of the base VI yields the compounds 105 (isoindoline structure) and 106. The 10-membered trans- (108b) and cis-dibenzazecine (106) were converted via 107 into a -allocryptopine (101b) in poor yield (Scheme 38). 

Hydrogen bonding plays a major part in all isoindoline structures. As a result, the molecules form 2-dimensional hydrogen bond networks. The structure of these networks reflects the hydrogen bond-forming capabilities of each species and their interplay with the respective molecular shape. As an example, in the structure of... 

Only after o-phthalodinitrile became available in high purity on an industrial scale from BASF the importance of these pigments was recognized. By improving the methods of synthesis and finishing it became possible to produce pigments with brilliant hues and better fastness properties. In 1973 BASF released the first isoindoline pigment into the market Lithol Fast Yellow 1840 (P.Y. 139). At the same time several other companies (Bayer, Ciba, Dainippon Ink) published novel isoindoline structures [8- 11]. 

The products from cyclization reactions of 5-substituted isoindolinediimirtes are 2,9,16,23-tetrasubstituted phthalocyanines, e.g. 2.110121,4lf Again, a mixture of four structural isomers is obtained (see p 737). It should be emphasized that reaction conditions employing isoindoline-diimines are mild in comparison to the use of phthalonitriles. 

Researchers at GlaxoSmithKline have numerous recent patent applications describing several series of H3 antagonists including the benzazapines (41) [115] and (42) [116], quinolizidines (43) [117], isoindolines (44) [118], and the piperidine amides (45) [119] and (46) [120]. All of these structures were disclosed as functional H3 antagonists. 

Carbonyl pigments of a variety of types may also be classed as high-performance products. These include some anthraquinones, quinac-ridones, perylenes, perinones, isoindolines and diketopyrrolopyrroles. The chemistry of these groups of colorant is discussed in Chapter 4. Some representative examples of chemical structures of important high-performance carbonyl pigments are illustrated in Figure 9.4. 

The common structural feature underlying these pigments is the isoindoline ring (X1, X3 = H2) ... 

More recent publications describe a variety of isoindoline pigments with different chemical structures. Such species comprise an isoindoline ring attached to two methine bridges. 

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... 

Cobalt(III)-alkyl peroxide complexes with the formula Co(BPI)(OOR)(OCOR ) (205 BPI = l,3-bis(2 -pyridylimino)isoindoline R= Bu , CMe2Ph R = Me, Ph, Bu ) have been prepared from the oxidation of Con(BPI)(OCOR ) complexes by alkyl hydroperoxides. The X-ray crystal structure of complex (205) (R=Bu R = Ph) revealed a distorted octahedral environment, with a monodendate OOBuc group and a bidendate carboxylate.635... 

Figure 7.11 General structure and composition of the 3200-member isoindoline SP pool library L2.

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-... 

Chlorthalidone (pKa = 9.4) is an example of a diuretic in this class of compounds that bears a structural analogy to the quinazolinones (Table 27.4). This compound may be named as a 1-oxo-isoindoline or a phthalimidine. Although the molecule exists primarily in the phthalimidine form, the ring may be opened to form a benzophenone derivative. 

Phthalocyanine (PCH2) is structurally similar to porphyrin (PHj) (see Fig. 1). The four isoindoline units are linked together in the 1,3-position by aza bridges to form a cyclic system. Formally, phthalocyanines are tetrabenzo-tetraazaporphyrins. 

Scheme 6.17. Synthesis of isoindolines and related structures via solid-supported [2 + 2 + 2] cyclotrimerization reactions. R = H, Bu, Ph, CH2OH, CH20Bn, CH2NHB0C, (CH2)3CN, SiMes, (CH2)4CI, C02Me, Et, CH20Me R = H, Et, CH20Me R = H, CH2OH R = H, Me, TMS Trt=trityl linker.

Figure 14—4 shows the structural formulae of these six isoindoline constitutions listed in the Colour Index. The pigments cover the range from greenish yellow (P.Y. 185), to reddish yellow (P.Y. 139), to orange (P.O. 66 and 69), red (P.R. 260) and brown (P.Br. 38). 

The status of isoindoline pigments up to the mid 1980s is summarized in l In the late 1980s two novel structures 14 and 15 were launched as regular sales products by BASF, namely P.O. 69 (Paliogen Orange L 3180 HD) and P.R. 260 (Paliogen Red L 3585 HD). 

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