Quinolines oxindoles

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Reactions of fluoroalkylketenimines which have been reported following these newly available synthetic approaches include hydrolysis and related additions of amines and alcohols, all of which occur at the olefinic bond. In contrast, the apparently similar addition of secondary phosphines occurs at the carbon-nitrogen double bond. These ketenimines appear to enter into cycloaddition reactions very readily with acetylenes they give quinolines, with nitrones they give oxindoles or oxadiazolidines (see p. 107), i > i and with isocyanides they yield iminoindolenines. These reactions are summarized in Scheme 54. 

Alkaloids can be divided into different t q3es according their pure chemical structures pointing first at the alkaloid base, a basic chemical nucleus. The following are basic types of alkaloids acridones, aromatics, carbo-lines, ephedras, ergots, imidazoles, indoles, bisindoles, indolizidines, manza-mines, oxindoles, quinolines, quinozolines. quinolizidines, phenylisoquinolines, phenylethylamines, piperidines, purines, pyrolidines, pyrrolizidines, pyrro-loindoles, pyrydines, sesquiterpenes, simple tetrahydroisoquinolines, stereoids, tropanes, terpenoids, diterpenes, and triterpenes. 

An aryne multicomponent reaction involving isoquinoline and 5-bromo-1-methylisatin resulted in spirooxazino isoquinolines (Scheme 66).The reaction occurs with a number of iV-substituted isatins. Quinoline can replace the isoquinoline as well. Carbonyls other than the isatins can trap the anion as well. A variety of aromatic, aliphatic, and heteroaromatic aldehydes can function as the electrophile. When pyridine replaces isoquinoUne as the nucleophilic trap, the reaction forms an oxindole but not an oxazino pyridine derivative (14SL608). 

Some indoline (14%) was also produced. Wr6bel employed diisobutylaluminum hydride (DIBAL) in an oxindole reduction to a pyrrolo[4,3,2- /e]quinoline (equation 4)... 

Myriad examples are known of oxindoles reacting to form indoles without prior carbonyl activation. Given (he vast scope of this subject, only a few early examples will be cited in addition to recent studies. Several groups have annulated oxindoles to access fused-indole heterocycles. Ila, Junjappa, and coworkers prepared pyrido[2,3-( ]indoles [61, 62] and 67/-indolo[2,3-fc]quinolines [63] using this approach (Scheme 9, equation 1). Adib and colleagues reported a simple synthesis of 9/7-pyrimido[4,5-Z ]indoles from oxindoles (eqnation 2) [64], and Bazgir and coworkers described a four-component one-pot a-carboUne synthesis... 

Indoles. A soln. of N-allyl-o-iodoaniline, 2.5 eqs. Na2C03, 1 eq. Bu4N CL, and a little Pd(OAc)2 in DMF stirred at 25° for 1 day - 3-methylindole. Y 97%. Quinolines and isoquinolines are also obtainable under these conditions. F.e. inch indolines and oxindoles, and bases. (NaOAc, EtjN), s. R.C. Larock, S. Babu, Tetrahedron Letters 28, 5291-4 (1987) review of palladium-catalyzed synthesis of condensed heteroarenes s. T. Sakamoto et al.. Heterocycles 27, 2225-49 (1988). 

Taylor and coworkers report a copper(II) 2-ethylhexanoate catalyst for the synthesis of oxindoles, thio-oxindoles, 3,4-dihydro-l//-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines from linear precursors by direct C(sp )-H and Ar-H coupling using atmospheric oxygen as the oxidant (Scheme 8.91). The reaction procedure is open to the air and easy to handle [162]. 

Scheme 8.91 Synthesis of oxindoles, thio-oxindoles, 3,4-dihydro-1H-quinolin-2-ones, and 1,2,3,4-tetrahydroqulnolines.

---