Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives.

ABSTRACT: A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm N,N-dimethylacetamide resulting in the formation of substituted quinolines. A degradation-build-up strategy of the ethyl ester at the 3-position allowed for the construction of the ?-hydroxyacetic acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project.

SUBMITTER: Jentsch NG

PROVIDER: S-EPMC6178280 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives.

Jentsch Nicholas G NG Hume Jared D JD Crull Emily B EB Beauti Samer M SM Pham Amy H AH Pigza Julie A JA Kessl Jacques J JJ Donahue Matthew G MG

Beilstein journal of organic chemistry 20180928

A convenient two-step synthesis of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate derivatives has been developed starting from commercially available 2-aminobenzoic acids. In step 1, the anthranilic acids are smoothly converted to isatoic anhydrides using solid triphosgene in THF. In step 2, the anhydride electrophiles are reacted with the sodium enolate of ethyl acetoacetate, generated from sodium hydroxide, in warm <i>N,N</i>-dimethylacetamide resulting in the formation of substituted quinoli ...[more]

PMID: 30344776

Similar Datasets

Convenient Novel Method to Access <i>N</i>-Benzylated Isatoic Anhydride: Reaction Behavior of Isatoic Anhydride with 4-Chlorobenzyl Chloride in the Presence of Bases.

Project description:Sodium hydride, potassium carbonate, and other bases are commonly used for N-alkylation of heterocyclic compounds. This report reveals the problems associated with N-benzylation of isatoic anhydride and identifies the plausible byproduct structures formed during the reaction. Subsequently, a novel breakthrough methodology has been developed using diisopropylamine and tetra butyl ammonium bromide. It gives excellent yields >88% in a short reaction time (2 h) at 30 °C with no byproducts, saving on processes as the pure product is directly obtained.

| S-EPMC8015103 | biostudies-literature

Green Synthesis of Substituted Anilines and Quinazolines from Isatoic Anhydride-8-amide.

Project description:Synthetic methods used to generate substituted anilines and quinazolines, both privileged pharmacological structures, are cumbersome, hazardous or, in some cases, unavailable. We developed a straightforward method for making isatoic anhydride-8-amide from isatin-7-carboxylic acid as a tool to easily produce a range of quinazoline and substituted aniline derivatives using adaptable pH-sensitive cyclization chemistry. The approaches are inexpensive, simple, fast, efficient at room temperature and scalable, enabling the synthesis of both established and new quinazolines and also highly substituted anilines including cyano derivatives.

| S-EPMC6776664 | biostudies-literature

8-Hydroxy-2-methylquinoline.

Project description:The asymmetric unit of the title compound, C(10)H(9)NO, contains two independent mol-ecules which are linked by a pair of O-H?N hydrogen bonds into a hydrogen-bonded dimer.

| S-EPMC2915051 | biostudies-other

Photochemical Generation of Benzoazetinone by UV Excitation of Matrix-Isolated Precursors: Isatin or Isatoic Anhydride.

Project description:Benzoazetinone was photochemically generated by UV irradiation of isatin isolated in low-temperature Ar matrixes. Upon UV (λ = 278 nm) excitation of isatin, monomers of the compound underwent decarbonylation and the remaining part of the molecule adopted the benzoazetinone structure or the structure of its open-ring isomer α-iminoketene. The same products (benzoazetinone and α-iminoketene) were generated by UV (λ = 278 nm) induced decarboxylation of matrix-isolated monomers of isatoic anhydride. Photoproduced α-iminoketene appeared in the low-temperature matrixes as a mixture of syn and anti isomers. Photoproducts generated upon λ = 278 nm irradiation of matrix-isolated isatin were subsequently exposed to λ = 532 nm light. That irradiation resulted in the shift of the α-iminoketene-benzoazetinone population ratio in favor of the latter closed-ring structure. The next irradiation at 305 nm caused the shift of the α-iminoketene-benzoazetinone population ratio in the opposite direction, that is, in favor of the open-ring isomer. Neither benzoazetinone nor its α-iminoketene open-ring isomer was generated upon UV (λ = 278 nm) irradiation of phthalimide isolated in Ar matrixes. Instead, the UV-excited monomers of this compound underwent such phototransformations as oxo → hydroxy phototautomerism or degradation of the five-membered ring with release of HNCO and CO. The efficiency of these photoconversions was low.

| S-EPMC7590977 | biostudies-literature

Acid-Catalyzed Synthesis of Isatoic Anhydride-8-Secondary Amides Enables IASA Transformations for Medicinal Chemistry.

Project description:Quinazolin-dione-N-3-alklyl derivatives are the core scaffolds for several categories of bioactive small molecules, but current synthetic methods are costly, involve environmental hazards, and are not uniformly scalable. Here, we report an inexpensive, flexible, and scalable method for the one-pot synthesis of substituted quinazolin-dione-N-3-alkyls (isomers of isatoic-8-secondary amides (IASAs)) from isatin that take advantage of in situ capture of imidic acid under acidic conditions. We further show that this method can be used for the synthesis of a wide variety of derivatives with medicinal uses.

| S-EPMC9107799 | biostudies-literature

2-(2-Hydroxy-ethyl)-3-[(2-hydroxy-ethyl)imino]isoindolin-1-one.

Project description:In the crystal structure of the title compound, C(12)H(14)N(2)O(3), mol-ecules are packed into layers parallel to (100). Each layer contains centrosymmetric dimers formed by a pair of strong O-H⋯N hydrogen bonds with an R(2) (2)(10) motif, while strong O-H⋯O hydrogen bonds forming C(10) chains connect mol-ecules into a two-dimensional network. Additional stabilization is supplied by weak C-H⋯O hydrogen bonds and weak π-π stacking inter-actions with centroid-centroid distances in the range 3.4220 (7)-3.9616 (7) Å.

| S-EPMC2970005 | biostudies-literature

Synthesis of ethyl (1S,2R,3S,4S,5S)-2,3-O-(isopropylidene)-4-hydroxy-bicyclo[3.1.0]hexane-carboxylate from L-ribose: a versatile chiral synthon for preparation of adenosine and P2 receptor ligands.

Project description:Substitution of the ribose moiety of various nucleosides and nucleotides with the (N)-methanocarba ring system increases the potency and selectivity as ligands at certain subtypes of adenosine and P2 receptors. We have prepared a key intermediate in the synthesis of these derivatives, ethyl (1S,2R,3S,4S,5S)-2,3-O-(isopropylidene)-4-hydroxybicyclo[3.1.0]hexane-carboxylate (15), starting from L-ribose (8) as a readily available, enantiopure building block. L-ribose was converted to the corresponding 5'-iodo derivative (9), which was cleaved reductively with Zn. Improvements were made in subsequent steps corresponding to a published route to biologically important (N)-methanocarba 5'-uronamido nucleosides, and new steps were added to prepare related 5'-nucleotides.

| S-EPMC6943831 | biostudies-literature

[N-(2-Hydroxy-ethyl)ethyl-enediamine]oxalatocopper(II).

Project description:In the title mononuclear copper(II) compound, [Cu(C(2)O(4))(C(4)H(12)N(2)O)], the Cu(II) ion has a slightly distorted square-pyramidal geometry, with a tridentate N-(2-hydroxy-ethyl)ethyl-enediamine (HydEt-en) and a bidentate oxalate (ox) ligand. The N atoms of the HydEt-en ligand and the O atoms of ox ligand form the basal plane, while the O atom of the ethanol group of the HydEt-en ligand is located in the axial position. The complex mol-ecules participate in a supra-molecular assembly through N-H⋯O and O-H⋯O hydrogen bonds between HydEt-en and ox ligands.

| S-EPMC2970959 | biostudies-literature

Domino Nitro Reduction-Friedlander Heterocyclization for the Preparation of Quinolines.

Project description:The Friedländer synthesis offers efficient access to substituted quinolines from 2-aminobenzaldehydes and activated ketones in the presence of a base. The disadvantage of this procedure lies in the fact that relatively few 2-aminobenzaldehyde derivatives are readily available. To overcome this problem, we report a modification of this process involving the in situ reduction of 2-nitrobenzaldehydes with Fe/AcOH in the presence of active methylene compounds (AMCs) to produce substituted quinolines in high yields. The conditions are mild enough to tolerate a wide range of functionality in both reacting partners and promote reactions not only with phenyl and benzyl ketones, but also with β-keto-esters, β-keto-nitriles, β-keto-sulfones and β-diketones. The reaction of 2-nitroaromatic ketones with unsymmetrical AMCs is less reliable, giving a competitive formation of substituted quinolin-2(1H)-ones from the cyclization of the Z Knoevenagel intermediate which appears to be favored when certain large groups are adjacent to the AMC ketone carbonyl.

| S-EPMC9268355 | biostudies-literature

?-Hydroxy-tetrahydroquinolines from Quinolines Using Chloroborane: Synthesis of the Peptidomimetic FISLE-412.

Project description:A new synthetic protocol provides a simple and direct method to generate functionalized ?-hydroxy-tetrahydroquinolines (THQs). Hydroboration of quinolines using chloroboranes followed by oxidation with NaBO3 ?H2 O led to the formation of functionalized ?-hydroxy THQs. High regio- and diastereoselectivities were observed in ? and ? substituted quinolines and the trans diastereomer of the ?-hydroxy-THQ was the major isostere. This new protocol was utilized to build the novel antibody-targeted lupus peptidomimetic, FISLE-412.

| S-EPMC6003427 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data