Acetylene derivatives of heterocycles

Shvartsberg, M. S.; Василевский, С. Ф.; Kostrovskii, V. G.; Kotlyarevskii, I. L.

doi:10.1007/bf00475858

Cited by 6 publications

(5 citation statements)

References 2 publications

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“…Compounds 5a [8] and 5b and 7 [9] were prepared as before. Their physicochemical properties agreed with those in the literature.…”

Section: Methodsmentioning

confidence: 99%

“…The preparation of cotarnine adducts with NH-acids such as aniline, phenylhydrazine, urea [2-4], and indoles [5] has been reported. Among the CH-acids, HCN [6], ketones (acetone and acetphenone), nitroalkanes (CH 3 NO 2 et al), nitrotoluenes, phenylacetonitrile [7], cyclic β-dicarbonyls [8,9], and compounds from certain other classes have been examined.The mechanism of the reaction is an aminoalkylation. The reaction products are cyclic Mannich bases [10].…”

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confidence: 99%

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Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

Краснов¹,

Карцев²,

Василевский

2005

Chem Nat Compd

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1 2a -d R 1 = H H 3 CO N O O CH 3 N N R 3 3a -d 4a, b a: R 1 = R 2 = R 3 = H b: R 1 = H, R 2 = R 3 = Me c: R 1 = R 2 = R 3 = Me d: R 1 = R 3 = H, R 2 = Me a: R 2 = R 3 = H b: R 2 = R 3 = Me c: R 2 = H, R 3 = Me d: R 2 = Me, R 3 = H a: R 3 = Me b: R 3 = H N O O N CH 3 N R 2 R 3 H 3 CO R 2 = Me OCH 3 1-Substituted 1,2,3,4-tetrahydroisoquinoline systems were prepared by reaction of cotarnine with the NHand CH-acids methyl-and acyl derivatives of pyrazole and 1,3-dicarbonyl reagents. Depending on the structure and reaction conditions, bifunctional pyrazole nucleophiles can give substitution products at the N atom, methyl, or acyl group; 1,3-diketones, at the terminal methyl. Rearrangements occurring during the reaction of cotarnine with bifunctional substrates were studied.6-Methyl-5-hydroxy-4-methoxy-5,6,7,8-tetrahydro-2H-1,3-methylenedioxy-[4,5-g]isoquinoline, or cotarnine (1), is a natural tautomeric pseudobase that is known to react with NH-and CH-acids to form the corresponding "anhydrocotarnyl derivatives" [1], which are of interest as structural analogs of isoquinoline plant alkaloids. The preparation of cotarnine adducts with NH-acids such as aniline, phenylhydrazine, urea [2-4], and indoles [5] has been reported. Among the CH-acids, HCN [6], ketones (acetone and acetphenone), nitroalkanes (CH 3 NO 2 et al.), nitrotoluenes, phenylacetonitrile [7], cyclic β-dicarbonyls [8,9], and compounds from certain other classes have been examined.The mechanism of the reaction is an aminoalkylation. The reaction products are cyclic Mannich bases [10]. The limited set of examined nucleophilic substrates must be noted because it leaves the synthetic possibilities of cotarnine and related pseudobases mostly unexplored. Reactions of cotarnine with bifunctional nucleophilic reagents are very little studied.In consideration of this and in continuation of studies of the synthesis of new analogs of isoquinoline alkaloids, we examined the reaction of 1 with a series of polyfunctional substrates including pyrazole, its methyl and acyl derivatives, and certain -dicarbonyls.The reaction of 1 with unsubstituted pyrazole (2a) in CH 3 OH at 30°C proceeded rapidly to form the aminoalkylation product of pyrazole at the N atom 3a. Considering the lability of cotarnine N-adducts, it can be assumed that electrophilic attack under more forcing conditions would lead to substitution at the C atom of the heteroaromatic ring, as occurred for indole [5]. However, 3a turned out to be stable and isomerization was not observed on boiling in aqueous alcohol for 1 d.

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“…Compounds 5a [8] and 5b and 7 [9] were prepared as before. Their physicochemical properties agreed with those in the literature.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

Краснов¹,

Карцев²,

Василевский

2005

Chem Nat Compd

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“…Hence the 1 H NMR spectrum of compound 5a in CDCl 3 or DMSO-d 6 (values for the chemical shifts for DMSO-d 6 solutions given in brackets) shows one set of signals, viz. for the protons of the enol multiple bond at 7.91 ppm (8.85), the pyrazole fragment at 6.15 (6.56), and the protons of the NCH 3 and CH 3 groups at 3.92 (3.83) and 2.50 (2.33) ppm respectively.…”

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confidence: 99%

“…EXPERIMENTAL 1 H and 19 F NMR spectra were recorded on Bruker AC-300 or AM-300 instruments (300 and 283 MHz respectively) at 298 K for solutions in CDCl 3 or DMSO-d 6 . TMS was used as internal standard for 1 H NMR spectra and CFCl 3 for 19 F NMR spectra (G 0.00).…”

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confidence: 99%

Modified method for the synthesis of isomeric N-substituted (1H-pyrazolyl)propane-1,3-diones

Taydakov

Krasnoselsky

2011

Chem Heterocycl Comp

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Heterocyclic 1,3-diketones are important intermediate compounds in organic synthesis and find widespread use as extracting agents, analytical reagents, and as ligands in coordination chemistry [1,2]. In terms of our current scientific plan in searching for novel heterocyclic ligands there arose the need to prepare a series of dibenzoylmethane analogs which contain different pyrazole substituents.A few reports are in the literature on these compounds synthesis. Most of the publications relate to the preparation of acyl pyrazolone derivatives [3, 4] but reported methods cannot be used for the preparation of the target compounds. The reaction of 1,3,4,6-tetracarbonyl compounds with hydrazines to give 1,3-diketones has also been reported [5] but this method is not universal and requires hardly obtainable starting materials.The most obvious route to synthesis of the pyrazole-containing diketones is a Claisen condensation of the corresponding carbonyl compounds in the presence of a base. This method has been little studied because of the relatively poor availability of pyrazole ketones. Data existing in the literature is restricted, in all, to a few examples, viz. the condensation of 1-(1,3,5-trimethyl-1H-pyrazol-4-yl)ethanone with ethyl acetate in the presence of sodium ethylate [6] and the reaction of ethyl 1-alkylacetyl-4-methyl-1H-pyrazole-5-carboxylates, also with ethyl acetate [7].We have previously reported a general method for the synthesis of isomeric pyrazolyl ketones. This work now relates to the reaction of compounds 1 with the pyrazole carboxylates 2 and with certain other esters in the presence of bases.

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“…Classical Friedel-Crafts conditions are not always suitable for acylation of pyrazoles. Satisfactory results were achieved with polyalkyl substituted compounds, 3 but in other cases the yields of ketones were dispiritingly low. 4 Moreover, some pyrazoles are unstable in the presence of AlCl 3 or, conversely, form complexes that are too stable and unreactive under these conditions.…”

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Direct Electrophilic Acylation of N-Substituted Pyrazoles by Anhydrides of Carboxylic Acids

Taydakov

Krasnoselskiy

2013

Synthesis

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A simple, convenient and scalable approach to 1-substituted 4-acylpyrazoles through direct acylation of pyrazoles by anhydrides of aliphatic, aromatic and fluorinated carboxylic acids in the presence of concentrated sulfuric acid as a catalyst is described. Target ketones were obtained in 41-86% isolated yields in high purity without laborious purification. The scope and limitations of the method are discussed.Substituted 4-acylpyrazoles are useful building blocks in heterocyclic chemistry, 1 and a lot of information about the utilization of pyrazole ketones as pharmaceutical intermediates is covered by patent literature. 1d Nevertheless, direct electrophilic introduction of an acyl fragment to the pyrazole ring has not been sufficiently investigated. Only a few examples of direct acylation have been described, some of which are summarized in Scheme 1.The earliest works, 2a,b from the beginning of the 20th century, required very drastic conditions (200-250°C, sealed tubes) to obtain the desired ketones 1 and 2, and the yields, where reported, were low. Of course, they are now only of historical interest. However, over the last several decades very little effort was made to improve this reaction. Classical Friedel-Crafts conditions are not always suitable for acylation of pyrazoles. Satisfactory results were achieved with polyalkyl substituted compounds, 3 but in other cases the yields of ketones were dispiritingly low. 4 Moreover, some pyrazoles are unstable in the presence of AlCl 3 or, conversely, form complexes that are too stable and unreactive under these conditions. Tin(II) chloride was also tested for this reaction as catalyst but with limited success. 5 A special class of direct acylation methods include reactions 6 with active acylation agents such as oxalyl chloride or oxalic acid methyl ester chloride. These reactions always require a large excess of acyl chloride and lead to formation of α-carbonyl compounds that are beyond the scope of this communication. Other synthetic approaches to 4-acylpyrazoles involve different transformations of the side chain, for example, reaction of organometallic reagents with pyrazolic Weinreb amides, 7 or a reversed strategy based on the interaction of aliphatic Weinreb amides with 4-pyrazolyllithium. 8 Both reactions require low temperatures, tetrahydrofuran as solvent, and strict protection against oxygen and moisture. Scheme 2 Synthesis of 4-acylpyrazole by side chain modificationAlternatively, pyrazolic aldehydes can be converted into secondary alcohols by the reaction with Grignard of organolithium reagents, followed by oxidation of alcohols 9

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Acetylene derivatives of heterocycles

Cited by 6 publications

References 2 publications

Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

Chemical Modification of Plant Alkaloids. 4. Reaction of Cotarnine with Bifunctional NH- and CH-Acids

Modified method for the synthesis of isomeric N-substituted (1H-pyrazolyl)propane-1,3-diones

Direct Electrophilic Acylation of N-Substituted Pyrazoles by Anhydrides of Carboxylic Acids

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