Isoquinoline applications

H-Thiazolo[3,4-6]isoquinoline, 1,5,10,1 Oa-tetrahydro-applications, 6, 709 Thiazolo[4,5-c]isoquinolines applications, 6, 710 Thiazolo[5,4-c]isoquinolines applications, 6, 710... 

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

The presence of a cyano group seems to be important[649]. The reaction has been successfully applied to halides of pyridine, quinoline, isoquinoline, and oxazoles[650]. An interesting application is the synthesis of tetracyanoquino-dimethane (789) by the reaction of / -diiodobenzene with malononitrile[65l]. 

Besides being useful precursors to pyrroles pyridine-2-ones -4-ones, -4-thiones. and -4-imines 4-alkylidene-dihydropyridines thiophenes 1,2,4-triazoles thiapyrane-2-thiones, isoquinoline-3-ones isoben-zothiophenes and 4-mercaptoimidazolium hydroxide inner salts, mesoionic thiazoles are potentially useful in the construction of molecules with herbicidic (39). central nerve stimulating, and antiinflammatory properties (40,41). Application in dye synthesis has likewise been reported (42). 

The application of the Hammett equation to bicyclic aromatic compounds of the quinoline and isoquinoline type may be envisaged in several ways. In quinoline, e.g., the homocyclic ring A in 9) may be... 

The relative configurations and predominant conformations of [l,2,3]oxathiazino[4,3- ]isoquinoline derivatives 177-182 were studied by means of H and 13C NMR spectroscopy with the applications of DNOE, 2D HSC, and 2D-COSY measurements. Their stereostructure includes an equilibrium between the conformers cis-1, trans and cis-2. In the /ra -structure, the B/C rings are trans-ane-WatcA with H-l lb and the N-5 lone electron pair trans-diaxial. In the cis structures, the hetero-rings are air-anellated in the cis-1 conformation C-l is in inside position, while in cis-2... 

Subsequently, in a patent application, isoquinoline glycinamides such as 2 were claimed as collagen PHD inhibitors [40], and an additional patent application claimed isoquinoline glycinamides as HIF PHD inhibitors [41]. 

A series of indeno[l,2-c]isoquinolines have been described [27] and INO-lOOl has been investigated in the clinic. Although the structure of INO-lOOl has not been reported, sulfonamide 28 is a representative structure (IC50 = lnM, EC5O = 10nM). CEP-9722 is in Phase I clinical trials, while its exact structure has not been disclosed, it is a prodrug of CEP-8983 (29) and patent applications highlight 30. Preclinical efficacy in combination with TMZ and camptothecin have been... 

Recently, Jankowski et al. [80] reported the application of MW to the Diels-Alder synthesis of N-methyloctahydroisoquinoline adducts, which are important intermediates in the synthesis of medicinally important compounds, such as HIV protease inhibitor isoquinoline carboxylate pharmaceuticals. The reaction of the arecoline 67 or its isomer 70 with Danishefsky s diene 68 in toluene (Scheme 4.32) was studied under both conventional and MW heating in sealed tubes, i. e. at elevated pressure. 

The chemistry of Reissert compounds has been the subject of numerous general reviews (3-10). In 1973 Popp gave a summary on the use of Reissert compounds in the synthesis of isoquinoline alkaloids and related compounds (7). We now wish to summarize new results that have appeared from 1973 to the end of 1985 for the application of Reissert compounds in the synthesis of isoquinoline as well as indole alkaloids. 

Among the great number of different approaches for the synthesis of phthal-ideisoquinoline alkaloids the application of Reissert compounds, developed first by Kerekes et al. (42,43), proved to be one of the most efficient and suitable methods (Scheme 24). Treatment of isoquinoline Reissert compounds 26 or 28 with sodium hydride in dimethylformamide resulted in the formation of the corresponding Reissert anions, which were reacted with dimethoxy- or meth-ylenedioxy-substituted o-formylbenzoic acid ester derivatives 178 and 179, respectively. The presumed mechanism of this reaction involves an initial reaction... 

In the early days, greatest interest was focused on the acid-catalyzed hydrolysis (by hydrochloric acid in the presence of 2,4-dinitrophenylhydrazine) of Reissert compounds to aldehydes and the corresponding heterocyclic carboxylic acid derivatives. This reaction is fairly general for compounds of quinoline (178) and isoquinoline (179) (Table 18), but it is not applicable to pyridines as they rarely form Reissert compounds. The 3-hydroxyquino-line Reissert compound does not yield benzaldehyde, probably because acylation of the 3-hydroxy group prevents formation of the required cyclic intermediate (180). Some nitroquinolines and isoquinolines give low yields of benzaldehyde. Rather curiously, disub-stituted quinoline Reissert compounds yield less of the aldehyde than of the corresponding... 

In the following sections structure, thermodynamic aspects, theoretical calculations, spectroscopic properties, reactions, syntheses, and, more briefly, the uses of these tricyclic ring systems are discussed. Within the individual subsections of reactivity, synthesis, and applications, the pyrim-ido[l,2-6]isoquinolines, pyrido[2,l-6]quinazolines, pyrimido[l,2-a]quino-lines, pyrido[l,2-a]quinazolines, and pyrimido[2,l-a]isoquinolines are considered. 

Table 4.84. Nitrogen Increments in Quinoline and Isoquinoline Relative to Naphthalene [73] (a) Application of these increments to Quinazoline (b) and 2,7-Naphthyridine (c).

Uses. Isoquinoline and isoquinoline derivatives are useful as corrosion inhibitors, antioxidants, pesticides, and catalysts. 1 hcy arc used in plating baths and miscellaneous applications, such as in photography, polymers, and azo dyes. Numerous derivatives have been prepared and evaluated as pharmaceuticals. Isoquinoline is a main component in quinoline still residue bases, which are sold as corrosion inhibitors and acid inhibitors for pickling iron and steel. 

Bose reported the dehalo genation of bromoanthracene, bromonaphthalene and several bromobenzenes under microwave-assisted hydrogen transfer conditions (ammonium formate, 10% Pd/C, ethylene glycol). An application of this reaction is the synthesis of several (3-lactams and isoquinoline derivatives14. 

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