The Synthesis of Some 4-Quinolinols and 4-Chloroquinolines by the Ethoxymethylenemalonic Ester Method¹

Abstract

The preparation of 4-alkylaminoquinolines is most conveniently accomplished by coupling the appropriate amine with a 4-haloquinoline. In this Laboratory three principal methods have been investigated for the preparation of 4-haloquinolines. The Meisenheimer2 procedure is not generally applicable and, for example, is entirely unsatisfactory as a method for the preparation of 4,7-dichloroquinoline and 4-chloro-8-quinolinesulfonic acid. The oxalacetic ester synthesis3 is perhaps more general in application than the Meisenheimer but the cyclization and decarboxylation steps require conditions which vary widely depending upon the substituents in the carbocyclic ring. The most general method thus far developed is the ethoxymethylenemalonic ester synthesis. Ring closure of the anilinomethylenemalonic ester was first employed by Gould and Jacobs4 to prepare 3-carboxy-4-quinolinol. The decarboxylation of this acid gives more uniform results than obtained, with the 2-carboxy-4quinolinol from the oxalacetic ester synthesis. This method of synthesis has been widely used among the antimalarial contractors and was de-

Synthesis of [14C]‐ and [13C6]‐labeled potent HIV non‐nucleoside reverse transcriptase inhibitor

“…Saponification, followed by decarboxylation, gave [ 13 C 6 ]4-hydroxyquinoline in 44% overall yield. [23][24][25][26] Mitsunobu's reaction with (2) and oxidation with m-CPBA as seen before gave [ 13 C 6 ]-(1) in 57% in two steps. The product was more than 99 at% 13 C.…”

Synthesis of 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic Acid

“…Subsequent N(1)-ethylation of 5 to obtain 6, followed by nitro-group reduction, produced the desired 6-amino-4-oxoquinoline 7. The preparation and satisfactory microanalysis of compounds 4 [37,38], 5 [37,38] and 6 [39,40] were previously reported, but their MS and NMR spectral data are lacking. Compound 7 was prepared (for use as synthon) by reduction of 6 with iron and ammonium chloride solution, but was not characterized [41].…”

“…Yield: 4.11 g (98 %); m. p. > 320 • C (lit. [38] C-3), 122.4 (C-4a), 123.6 (C-8), 124.0 (C-5), 133.0 (C-7), 144.1 (C-8a), 149.6 (C-6), 150.4 (C-2), 169.3 (CO 2 Et), 176.9 (C-4).…”

Synthesis and Analgesic Activity of Some Quinazoline Analogs of Anpirtoline

“…The following starting compounds were prepared according to the previously described methods: piperidin-4-ylthiole [1] , 1-methylpiperidin-4-ylthiole [1,6] , 4,7-dichloroquinazoline [7] , 4-chloroquinoline [8] , and 4,7-dichloroquinoline [9] .…”