scholarly journals The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

2019 ◽  
Vol 15 ◽  
pp. 655-678 ◽  
Author(s):  
Tilman Lechel ◽  
Roopender Kumar ◽  
Mrinal K Bera ◽  
Reinhold Zimmer ◽  
Hans-Ulrich Reissig
Keyword(s):  
Carboxylic Acids ◽  
Functional Groups ◽  
Condensation Reaction ◽  
Hydroxylamine Hydrochloride ◽  
Dicarboxylic Acids ◽  
Alkoxy Group ◽  
Alternative Methods ◽  
Substitution Pattern ◽  
Three Component Reaction ◽  
Acid Labile

The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible.

Microbial Reduction of Aromatic Carboxylic Acids

1993 ◽  
Vol 48 (1-2) ◽  
pp. 52-57 ◽  
Author(s):  
Hans-Adolf Arfmann ◽  
Wolf-Rainer Abraham
Keyword(s):  
Carboxylic Acids ◽  
Phenylacetic Acid ◽  
General Rule ◽  
Dicarboxylic Acids ◽  
Microbial Reduction ◽  
Substitution Pattern ◽  
Aromatic Carboxylic Acids

Several benzoic, cinnamic and phenylacetic acid derivatives were screened with 20 microorganisms, mainly fungi, for the reduction of their carboxylic function. For all organisms several compounds were reduced in fairly good yields up to 80% to the corresponding alcohol. No general rule could be established, concerning the substitution pattern, as to which compounds were transformed to the alcohol. Generally the reactions were accomplished within 48-70h. Only minor, if any, side products were detected. Dicarboxylic acids, such as phthalic or phenylglutaric acids and similar compounds could not be reduced by the microorganisms tested.

scholarly journals The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

2014 ◽  
Vol 10 ◽  
pp. 394-404 ◽  
Author(s):  
Mrinal K Bera ◽  
Moisés Domínguez ◽  
Paul Hommes ◽  
Hans-Ulrich Reissig
Keyword(s):  
Dft Calculations ◽  
Carboxylic Acids ◽  
Aromatic Compounds ◽  
Dicarboxylic Acids ◽  
Membered Ring ◽  
Simple Synthesis ◽  
Pyrimidine Derivatives ◽  
Three Component Reaction ◽  
Palladium Catalyzed ◽  
Pyridine And Pyrimidine Derivatives

An extension of the substrate scope of the Flögel-three-component reaction of lithiated alkoxyallenes, nitriles and carboxylic acids is presented. The use of dicarboxylic acids allowed the preparation of symmetrical bis(β-ketoenamides) from simple starting materials in moderate yields. Cyclocondensations of these enamides to 4-hydroxypyridine derivatives or to functionalized pyrimidines efficiently provided symmetrically and unsymmetrically substituted fairly complex (hetero)aromatic compounds containing up to six conjugated aryl and hetaryl groups. In addition, subsequent functionalizations of the obtained heterocycles by palladium-catalyzed couplings or by oxidations are reported. We also describe the simple synthesis of a structurally interesting macrocyclic bispyrimidine derivative incorporating a 17-membered ring, whose configuration was elucidated by DFT calculations and by subsequent reactions.

Access to Highly Substituted Pyrimidine N-Oxides and 4-Acetoxymethyl-Substituted Pyrimidines via the LANCA Three-Component Reaction–Cyclocondensation Sequence

Synthesis ◽  
2021 ◽  
Author(s):  
Reinhold Zimmer ◽  
Hans-Ulrich Reissig ◽  
Luise Schefzig ◽  
Timon Kurzawa ◽  
Giaime Rancan ◽  
...  
Keyword(s):  
Carboxylic Acids ◽  
Room Temperature ◽  
Hydroxylamine Hydrochloride ◽  
Trifluoroacetic Anhydride ◽  
Pyrimidine Derivatives ◽  
Mild Conditions ◽  
Structural Variety ◽  
Three Component Reaction ◽  
Sterically Demanding ◽  
Synthetic Utility

AbstractThe LANCA three-component reaction of lithiated alkoxy­allenes (LA), nitriles (N), and carboxylic acids (CA) smoothly provides β-alkoxy-β-ketoenamides in broad structural variety. The subsequent cyclocondensation of these compounds with hydroxylamine hydrochloride afforded a large library of pyrimidine N-oxides under mild conditions and in good yields. Their synthetic utility was further increased by the Boekelheide rearrangement leading to 4-acetoxymethyl-substituted pyrimidines. With trifluoroacetic anhydride the rearrangement proceeds even at room temperature and directly furnishes 4-hydroxymethyl-substituted pyrimidine derivatives. The key reactions are very robust and work well even in the presence of sterically demanding substituents.

Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage–Independent Activation of Strong C–O Bonds

2018 ◽  
Author(s):  
Erin Stache ◽  
Alyssa B. Ertel ◽  
Tomislav Rovis ◽  
Abigail G. Doyle
Keyword(s):  
Carboxylic Acids ◽  
Functional Groups ◽  
Single Step ◽  
Direct Access ◽  
Photoredox Catalysis ◽  
Acyl Radical ◽  
Synthetic Strategy ◽  
Acyl Radicals ◽  
Benzyl Radicals ◽  
Aliphatic Carboxylic Acids

Alcohols and carboxylic acids are ubiquitous functional groups found in organic molecules that could serve as radical precursors, but C–O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen centered nucleophile. We first show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H-atom trapping to afford the deoxygenated product. Using the same method, we demonstrate access to synthetically versatile acyl radicals which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge new C–O, C–N and C–C bonds in a single step.

Synthesis of 3-(Cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8- carboxylic Acids Via an Efficient Three-component Condensation Reaction between Cyclohexylisocyanide and 2-Aminopyridine-3-carboxylic Acid in the Presence of Aromatic Aldehyde

2018 ◽  
Vol 21 (4) ◽  
pp. 298-301 ◽  
Author(s):  
Ghasem Marandi
Keyword(s):  
Biological Sciences ◽  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
High Performance ◽  
Condensation Reaction ◽  
Aromatic Aldehydes ◽  
New Materials ◽  
One Pot ◽  
High Yields ◽  
Benzaldehyde Derivatives

Aim and Objective: The reaction of cyclohexylisocyanide and 2-aminopyridine-3- carboxylic acid in the presence of benzaldehyde derivatives in ethanol led to 3-(cyclohexylamino)-2- arylimidazo[1,2-a]pyridine-8-carboxylic acids in high yields. In a three component condensation reaction, isocyanide reacts with 2-aminopyridine-3-carboxylic acid and aromatic aldehydes without any prior activation. Material and Methods: The synthesized products have stable structures which have been characterized by IR, 1H, 13C and Mass spectroscopy as well as CHN-O analysis. Results: In continuation of our attempts to develop simple one-pot routes for the synthesis of 3- (cyclohexylamino)-2-arylimidazo[1,2-a]pyridine-8-carboxylic acids, aromatic aldehydes with divers substituted show a high performance. Conclusion: In conclusion, this study introduces the art of combinatorial chemistry using a simple one-pot procedure for the synthesis of new materials which are interesting compounds in medicinal and biological sciences.

Biological Activity of Novel N-Substituted Amides of endo-3- (3-Methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene-2- carboxylic Acid and N-Substituted Amides of 1-(5-Methylthio- 1,2,4-triazol-3-yl)cyclohexane-2-carboxylic Acids

2012 ◽  
Vol 67 (3-4) ◽  
pp. 123-128
Author(s):  
Anna Pachuta-Stec ◽  
Urszula Kosikowska ◽  
Anna Chodkowska ◽  
Monika Pitucha ◽  
Anna Malm ◽  
...  
Keyword(s):  
Biological Activity ◽  
Carboxylic Acid ◽  
Carboxylic Acids ◽  
Condensation Reaction ◽  
Primary Amines ◽  
Pharmacological Activities

N-Substituted amides of endo-3-(3-methylthio-1,2,4-triazol-5-yl)bicyclo[2.2.1]hept-5-ene- 2-carboxylic acid and 1-(5-methylthio-1,2,4-triazol-3-yl)cyclohexane-2-carboxylic acid were prepared by the condensation reaction of endo-S-methyl-N1-(bicyclo[2.2.1]hept-5-ene-2,3- dicarbonyl)isothiosemicarbazide and S-methyl-N1-(cyclohexane-2,3-dicarbonyl)isothiosemicarbazide with primary amines. The synthesized compounds were screened for their microbiological and pharmacological activities

Field desorption mass spectrometry of carboxylic acids: characteristic spectra and analysis of mixtures and impure samples

1978 ◽  
Vol 56 (10) ◽  
pp. 1372-1377 ◽  
Author(s):  
Gordon Walter Wooo ◽  
Emily Jane Oldenburg ◽  
Pui-Yan Lau ◽  
Donna Lee Wade
Keyword(s):  
Carboxylic Acids ◽  
Dicarboxylic Acids ◽  
Cross Product ◽  
Molecular Ions ◽  
Base Peak ◽  
Field Desorption ◽  
Technical Grade ◽  
Molecular Ion ◽  
Field Desorption Mass Spectrometry ◽  
Anode Temperature

Field desorption mass spectra were obtained for a variety of saturated and unsaturated carboxylic acids containing 12 or more carbons. At best anode temperature molecular ions were dominant and small peaks representing [M + 1]+, [2M + 1]+, [M − 17]+, and [Formula: see text] were present in several compounds. At higher temperatures several novel ions were found, including one corresponding to [2M + 1 – 18]+ which may represent anhydride formation. In a mixture of cis-5-eicosenoic and elaidic acids each molecular ion desorbed as expected but at higher temperatures the three possible anhydride ions appeared, with the cross product [M1 + M2 + 1 − H2O]+ as the base peak. Isomeric hydroxystearic acids (2-OH, 12-OH, 17-OH) gave predominantly ions in the molecular ion region with some differences in spectra which may relate to structure. Apparent polyester formation has been observed in 3-hydroxypropanoic acid where ions of the general formula [xM − (x − 1)H2O + H]+ with x = 2, 3, … 13 were found. Several other hydroxyacids show dimer formation and lactic acid has ions up to x = 5 in the above formula. Two of four technical grade dicarboxylic acids tested were seriously contaminated by sodium ions and gave useful spectra only after extraction by dibenzo-18-crown-6 ether. After this treatment both adipic and azelaic acid have [M + 1]+ as base peak, although adipic acid decarboxylates readily ([Formula: see text] = 74%) Other technical grade acids showed the presence of homologues and related structures as impurities.

Consecutive Multicomponent Reactions: Synthesis of 3-Acyl-4-alkynyl-Substituted 1,3-Thiazolidines

Synthesis ◽  
2018 ◽  
Vol 50 (05) ◽  
pp. 1123-1132 ◽  
Author(s):  
Jürgen Martens ◽  
Torben Schlüter ◽  
Nils Frerichs ◽  
Marc Schmidtmann
Keyword(s):  
Functional Groups ◽  
Multicomponent Reactions ◽  
Terminal Alkynes ◽  
Synthetic Route ◽  
Acyl Chlorides ◽  
Mild Conditions ◽  
Three Component Reaction

This work describes the synthesis of compounds containing thiazolidine and propargylamidic motifs. Their preparation follows a synthetic route containing two multicomponent reactions. First, the Asinger four-component reaction is used to prepare 3-thiazolines and 3-oxazolines. Secondly, these heterocyclic imines are converted into propargylamides by a copper-catalyzed three-component reaction using acyl chlorides and terminal alkynes. The synthetic route is characterized by mild conditions and many functional groups are tolerated. The formation of an unexpected α-alkynoxyamide is also presented.

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