Reactions of adamantyl-substituted keto esters with hydrazine and phenylhydrazine

Бормашева, К. М.; Nechaeva, O. N.; Моисеев, И. К.

doi:10.1134/s1070428008120063

Cited by 9 publications

(10 citation statements)

References 6 publications

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“…Moreover, in contrast to 1-adamantylacetic acid (1), which gave TFAA-insoluble anhydride 2, mixed anhydrides 25·CF 3 CO 2 H and 26·CF 3 CO 2 H remained dissolved in the reaction mixture, so they were not separated as pure compounds, but reacted directly with HO and NH nucleophiles (Scheme 4). As a result, 2,4-bis(tert-butyl)acetoacetic acid (27), [31] its phenyl ester 28, and N-benzylamide 29, as well as phenyl ester 30 were obtained in moderate to good yield. In the case of β-keto acid 27, the sample obtained contained up to 10 % of 1,3-bis(tert-butyl)acetone (31), which formed easily from 27 upon heating under acidic conditions.…”

Section: Resultsmentioning

confidence: 97%

“…As for adamantane-containing β-keto acids, these compounds were synthesized in the form of the corresponding esters 19-21 by the acylation of malonic ester with 1-adamantanecarboxylic acid chloride [20] or 1-adamantylacetic acid chloride [21] or by the adamantylation of β-keto esters with 1-bromo- [22,23] or 1-hydroxyadamantanes. [24] These adamantylated keto esters were used in the synthesis of depsipeptides [25] and various heterocycles [21,22,24,26,27] including biologically active ones.…”

Section: Resultsmentioning

confidence: 99%

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Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives

et al. 2010

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The self‐acylation of 1‐adamantylacetic acid (1) in trifluoroacetic anhydride, catalyzed by triflic acid, proceeds through the formation of the mixed 2,4‐bis(1‐adamantyl)acetoacetic–trifluoroacetic anhydride 2, and it was used as an efficient approach to previously unknown 2,4‐bis(1‐adamantyl)acetoacetic acid (3), its esters 4–6 and amides 7–11, and the sterically hindered 1‐adamantyl(1‐adamantylacetyl)ketene (12). The latter is stable in solution and can be isolated as a neat solid. Addition of methanol or primary amines to 12 gave the corresponding derivatives of acid 3. Acid 3 was decarboxylated to 1,3‐bis(1‐adamantyl)acetone (22), whereas theheterocyclization of phenyl ester 6 with thiourea gave two isomeric adamantylated thiouracils 23 and 24. The structures of N‐benzylamide 7 and thiouracil 23 were confirmed by single‐crystal X‐ray analysis. The utilization of the self‐acylation method for the conversion of some other aliphatic acids is discussed and preliminarily tested.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives

et al. 2010

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“…N-Phenyl-3-adamantyl-and N-phenyl-3-adamantylmethylpyrazolones were synthesized for the first time from the corresponding oxo esters [6,7]. Later on, reactions of dioxo esters with hydrazine and phenylhydrazine were reported [8,9]. It was found that, depending on the initial ester structure, either adamantanecarboxylic acid hydrazide or 3-(1-adamantylmethyl)-4,5-dihydro-1H-pyrazol-5-one and 3-(1-adamantylmethyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-one were formed.…”

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confidence: 99%

“…It was found that, depending on the initial ester structure, either adamantanecarboxylic acid hydrazide or 3-(1-adamantylmethyl)-4,5-dihydro-1H-pyrazol-5-one and 3-(1-adamantylmethyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-one were formed. The reaction of ethyl 3-(1-adamantyl)-2-(1-adamantylcarbonyl)-3-oxopropanoate with hydrazine gave ethyl 3,5-bis(1-adamantyl)-1H-pyrazole-4-carboxylate [8].…”

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confidence: 99%

Synthesis of pyrazoles and pyrazolones from 1,3- and 1,4-diketones of the adamantane series

Коньков

Моисеев

2009

Russ J Org Chem

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Various pyrazole and dihydropyrazolones containing an adamantane fragment were synthesized from adamantyl-substituted 1,3-and 1,4-diketones, ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates (R = CN, Ac), and ethyl 2-(1-adamantylcarbonyl)-4-oxo-4-phenylbutanoate.Methods of synthesis and chemical properties of 1,2-diazoles and their derivatives have been well documented [1][2][3][4][5]. Compounds of this series attract interest as pyrazolone dyes and drugs. Examples of the latter are Phenazone, Aminophenazone, and Metamizole sodium. However, there are only a few publications on the synthesis of 1,2-diazoles and pyrazolones having an adamantane fragment. N-Phenyl-3-adamantyl-and N-phenyl-3-adamantylmethylpyrazolones were synthesized for the first time from the corresponding oxo esters [6,7]. Later on, reactions of dioxo esters with hydrazine and phenylhydrazine were reported [8,9]. It was found that, depending on the initial ester structure, either adamantanecarboxylic acid hydrazide or 3-(1-adamantylmethyl)-4,5-dihydro-1H-pyrazol-5-one and 3-(1-adamantylmethyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-one were formed. The reaction of ethyl 3-(1-adamantyl)-2-(1-adamantylcarbonyl)-3-oxopropanoate with hydrazine gave ethyl 3,5-bis(1-adamantyl)-1H-pyrazole-4-carboxylate [8].In this paper we describe the synthesis of heterocyclic compounds on the basis of 1,3-and 1,4-diketones of the adamantane series, as well as from ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates [R = CN, Ac] and ethyl 2-(1-adamantylcarbonyl)-4-oxo-4-phenylbutanoate. Known procedures for the preparation of 1,3-diketones are based on the Claisen condensation, i.e., acylation of ketones with esters in the presence of strong bases such as metallic sodium, sodium hydride, sodium amide, and others [10], reaction of ketones with carboxylic acid anhydrides in the presence of boron trifluoride-ether complex [11,12], acylation of ketones (preliminarily treated with lithium diisopropylamide and chlorotrimethylsilane) with carboxylic acid chlorides in the presence of Lewis acids (TiCl 4 , SnCl 4 , ZnCl 2 ) [13], and acylation of ketones with carboxylic acid anhydrides in the presence of ZnCl 2 and SiCl 4 [14]. We synthesized adamantyl-substituted 1,3-diketones I and II by reaction of 1-adamantyl methyl ketone with carboxylic acid anhydrides catalyzed by boron trifluoride-ether complex (Scheme 1). However, we failed to obtain the corresponding 1,3-diketone from adamantane-1-carboxylic anhydride under analogous conditions. We also tried to perform acylation of 1-adamantyl methyl ketone with carboxylic acid anhydrides in the presence of ZnCl 2 and SiCl 4 in boiling methylene chloride, but the yields were lower than in the reactions catalyzed by BF 3 · Et 2 O.Ethyl 4-(1-adamantyl)-2-R-4-oxobutanoates III and IV (R= CN, Ac) were obtained by reactions of (1-ada-

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“…The reaction afforded the desired product (3) in 93% yield (Scheme 1). The compound was identified by comparing its mp to the published value [30] . The 1 H-NMR spectra of (3) confirmed substitution of the methoxy group by hydrazine, as it showed signals from the amine hydrogens and the absence of the signal from a methyl group.…”

Section: Preparation Of Adamantane-1-carboxylic Acid Hydrazide (3)mentioning

confidence: 99%

In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

et al. 2015

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Aim: To investigate the binding mode of synthesized adamantly derivatives inside of cholinesterase enzymes using molecular docking simulations. Methods: A series of hybrid compounds containing adamantane and hydrazide moieties was designed and synthesized. Their inhibitory activities against acetylcholinesterase (AChE) and (butyrylcholinesterase) BChE were assessed in vitro. The binding mode of the compounds inside cholinesterase enzymes was investigated using Surflex-Dock package of Sybyl7.3 software. Results: A total of 26 adamantyl derivatives were synthesized. Among them, adamantane-1-carboxylic acid hydrazide had an almost equal inhibitory activity towards both enzymes, whereas 10 other compounds exhibited moderate inhibitory activity against BChE. The molecular docking studies demonstrated that hydrophobic interactions between the compounds and their surrounding residues in the active site played predominant roles, while hydrophilic interactions were also found. When the compounds were docked inside each enzyme, they exhibited stronger interactions with BChE over AChE, possibly due to the larger active site of BChE. The binding affinities of the compounds for BChE and AChE estimated were in agreement with the experimental data. Conclusion:The new adamantly derivatives selectively inhibit BChE with respect to AChE, thus making them good candidates for testing the hypothesis that BChE inhibitors would be more efficient and better tolerated than AChE inhibitors in the treatment of Alzheimer's disease.

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Reactions of adamantyl-substituted keto esters with hydrazine and phenylhydrazine

Cited by 9 publications

References 6 publications

Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives

Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives

Synthesis of pyrazoles and pyrazolones from 1,3- and 1,4-diketones of the adamantane series

In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes

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