General Method of Synthesis for Natural Long-Chain β/-Diketones

Barbieri, G.; Seoane, Gustavo; Trabazo, Jose-Luis; Riva, A. Guillarte; Umpierrez, F.; Radesca, Lilian; Tubio, Ramon; Kwart, L. D.; Hudlický, Tomáš

doi:10.1021/np50052a012

Cited by 8 publications

(3 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are methods to synthesize β-keto esters from esters [34-37] (Claisen condensation) and aldehydes [38,39], but these methods have main limitation in varying the substituents. Often, a number of methods such as acylation of enolates of malonates [40,41], acylation of Meldrum's acid [42-45], mixed malonate esters [46,47] and bistrimethylsilylmalonate [48,49] have a chelating effect employed to lock the enolate anion of malonate using lithium and magnesium salts [50,51]; however, these methods suffer from inconsistent yields in the case of aliphatic acylation. There are methods to synthesize β-keto esters from ketones like caboxylation of ketone enolates [52-54] using carbon dioxide and carbon monoxide sources in the presence of palladium or transition metal catalysts.…”

Section: Introductionmentioning

confidence: 99%

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

et al. 2013

View full text Add to dashboard Cite

BackgroundPyrazolones are traditionally synthesized by the reaction of β-keto esters with hydrazine and its derivatives. There are methods to synthesize β-keto esters from esters and aldehydes, but these methods have main limitation in varying the substituents. Often, there are a number of methods such as acylation of enolates in which a chelating effect has been employed to lock the enolate anion using lithium and magnesium salts; however, these methods suffer from inconsistent yields in the case of aliphatic acylation. There are methods to synthesize β-keto esters from ketones like caboxylation of ketone enolates using carbon dioxide and carbon monoxide sources in the presence of palladium or transition metal catalysts. Currently, the most general and simple method to synthesize β-keto ester is the reaction of dimethyl or ethyl carbonate with ketone in the presence of strong bases which also requires long reaction time, use of excessive amount of reagent and inconsistent yield. These factors lead us to develop a simple method to synthesize β-keto esters by changing the base and reagent.ResultsA series of β-keto esters were synthesized from ketones and ethyl chloroformate in the presence of base which in turn are converted to pyrazolones and then subjected to cytotoxicity studies towards various cancer cell lines and antimicrobial activity studies towards various bacterial and fungal strains.ConclusionThe β-keto esters from ethyl chloroformate was successfully attempted, and the developed method is simple, fast and applicable to the ketones having the alkyl halogens, protecting groups like Boc and Cbz that were tolerated and proved to be useful in the synthesis of fused bicyclic and tricyclic pyrazolones efficiently using cyclic ketones. Since this method is successful for different ketones, it can be useful for the synthesis of pharmaceutically important pyrazolones also. The synthesized pyrazolones were subjected to antimicrobial, docking and cytotoxicity assay against ACHN (human renal cell carcinoma), Panc-1 (human pancreatic adenocarcinoma) and HCT-116 (human colon cancer) cell line, and lead molecules have been identified. Some of the compounds are found to have promising activity against different bacterial and fungal strains tested.

show abstract

Section: Introductionmentioning

confidence: 99%

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

et al. 2013

View full text Add to dashboard Cite

show abstract

“…However, 81% of the concomitantly present TMSE bketo ester 4a did so too. Attempted demethylation of a mixture of the same b-keto esters with lithium iodide in N,N-dimethylformamide at 140°C 16 gave a plethora of products. A conversion of 100% of methyl b-keto ester 7a into ketone 6a was induced by heating a mixture of b-keto esters 7a and 4a, benzenethiol, and either cesium carbonate 17 or potassium carbonate (Table 5).…”

mentioning

confidence: 99%

“…23 In the second part of our investigation, we studied the feasibility of chemoselective cleavages/decarboxylations of mixed bis(b-keto esters) 16-19 (Scheme 5). These feature a TMSE b-keto ester moiety and a methyl-, tert-butyl-, allyl-, or benzyl b-keto ester moiety (16)(17)(18)(19), respectively, Scheme 5). It is possible that ester derivatives of these would have to be tolerated on the access route to these compounds (Scheme 6).…”

mentioning

confidence: 99%

β-Keto Esters Derived from 2-(Trimethylsilyl)ethanol: An Orthogonal Protective Group for β-Keto Esters

Knobloch¹,

Brückner²

2008

Synthesis

View full text Add to dashboard Cite

b-Keto esters derived from 2-(trimethylsilyl)ethanol undergo cleavage and decarboxylation when treated with 0.75 equivalents of tetrabutylammonium fluoride trihydrate in tetrahydrofuran at 50°C, while b-keto esters derived from methanol, tert-butyl alcohol, allyl alcohol, or benzyl alcohol stay intact. Conversely, methyl-, tert-butyl-, allyl-, or benzyl b-keto esters can be cleaved and decarboxylated without the 2-(trimethylsilyl)ethyl b-keto esters being affected. Similarly, mixed bis(b-keto esters) derived from 2-(trimethylsilyl)ethanol and methanol, tert-butyl alcohol, allyl alcohol, or benzyl alcohol can be defunctionalized chemoselectively under the same reaction conditions. An ongoing project requires the transformation of an unsymmetric bis(b-keto ester) 1 into a chain-shortened b-hydroxy (w-1)-keto ester of generic structure 2 (Scheme 1). This implies the need for ester differentiation -and more processing thereafter -either at the bis(b-keto ester) stage or in the bis(b-hydroxy ester) 3, which should be derivable from 1 by the asymmetric hydrogenation of both bketo ester moieties. With regard to the feasibility of the first approach, we discovered a while ago that b-keto esters with an electron-donating substituent R 1 can be hydrogenated asymmetrically without a b-keto ester with an electron-withdrawing substituent R 2 being affected. 1 Scheme 1Continuing to explore b-keto ester differentiation, we recently reported 2 that b-keto esters 4a-c derived from 2-(trimethylsilyl)ethanol ('TMS-ethanol') can be deprotected/decarboxylated quantitatively in tetrahydrofuran solution by exposure to 0.75 equivalents of tetrabutylammonium fluoride trihydrate (50°C, several h), 3 giving ketones 5a-c (Scheme 2). These conditions left analogous b-keto esters 7a-c derived from methanol, b-keto esters 8a-c derived from tert-butyl alcohol, b-keto esters 9a-c derived from allyl alcohol, and b-keto esters 10a-c derived from benzyl alcohol (Scheme 2) almost untouched.Scheme 2 Goal I of chemoselective b-keto ester deprotection/ decarboxylation reactions (upper reaction): defunctionalizing TMSE b-keto esters 4 without analogous methyl-, tert-butyl-, benzyl-, or allyl b-keto esters 7-10 being affected. Goal II: achieving the opposite selectivities. [TMSE = (CH 2 ) 2 TMS; Biph = p-PhC 6 H 4 (biphenyl-4-yl)]Here we provide full experimental details for these reactions. In addition, we show that b-keto ester deprotections/decarboxylations with reversed chemoselectivities are, in general, feasible, too: the mentioned methyl b-keto esters 7a-c, tert-butyl b-keto esters 8a-c, allyl b-keto esters 9a-c, and benzyl b-keto esters 10a-c were decarboxylated to give ketones 6a-c without much of their 2-(trimethylsilyl)ethyl b-keto ester (TMSE b-keto ester) counterparts 7a-c being affected (Scheme 2). Moreover, we present here the extension of these reactions from intermolecularly to intramolecularly competing deprotections/decarboxylations of two b-keto ester moieties.

show abstract

ChemInform Abstract: General Method of Synthesis for Natural Long‐Chain β‐Diketones.

Barbieri

Seoane²,

Trabazo³

et al. 1988

ChemInform

View full text Add to dashboard Cite

show abstract

General Method of Synthesis for Natural Long-Chain β/-Diketones

Cited by 8 publications

References 9 publications

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

β-Keto Esters Derived from 2-(Trimethylsilyl)ethanol: An Orthogonal Protective Group for β-Keto Esters

ChemInform Abstract: General Method of Synthesis for Natural Long‐Chain β‐Diketones.

Contact Info

Product

Resources

About