Acylation of diethyl (ethoxycarbonylfuryl)methanephosphonates under the conditions of claisen reaction

O,O-Diethyl (ethoxycarbonylfuryl)methanephosphonates are formylated with ethyl formate in the presence of sodium foil at the methylene group adjacent to phosphorus atom to form sodium salts of phosphonoacetic aldehyde. When the substituents in the furan ring are remote from one another, and also in the case of 3, 4-disubstituted isomer these salts in DMSO solution exist in the carbanion form. Anions of salts of (2-ethoxycarbonylfur-3-yl)phosphonoacetic aldehyde and the isomer with the reversed location of substituents in DMSO solution take part in the dynamic equilibrium between the carbanion and the enolate form. The alkylation of all salts obtained with allyl bromide and dimethyl sulfate proceeds exclusively at the oxygen to form a mixture of Z- and E-isomers of phosphorylated vinyl ethers.     

Formylation of alkyl cyanofurylmethanphosphonates at the active methylene group

Alkyl cyanofurylmethanephosphonates are formylated with ethyl formate in the presence of sodium foil to form sodium derivatives of phosphonoacetic aldehyde. If phosphonoacetic aldehyde and nitrile groups occupy remote positions in the furan ring, the sodium derivative in DMSO solution exists in the form of carbanion carrying charge on the carbon atom adjacent to the aldehyde group. If the substituents are located at the adjacent carbons of furan ring, the solution equilibrium between the carbanionic (major product) and Z-enolate forms of salts is established. Alkylation of the formed salts with methyl iodide occurs exclusively at the oxygen atom to give methyl enolates. In most cases, a mixture of E-and Z-isomers is formed, the E one being prevailing. In the case of 2,5-location of the substituents in furan ring, the sodium salt is inactive, and the alkylation does not occur.     

Nucleophilic Substitution Reaction of p-Dinitrobenzene by a Carbanion: Evidence for Electron Transfer Mechanism

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Tosyiate of ethyl 3-amino-2-phenyliodoniocrotonate: Synthesis, crystal structure, and synthesis of heterocyclic compounds based on it

Ethyl 3-aminocrotonate, when reacted with hydroxy(tosyloxy)iodobenzene, forms the tosylate of ethyl 3-amino-2-phenyliodoniocrotonate which crystallizes well in up to 80% yield. X-ray analysis confirms the structure of the phenyliodonium salt, revealing intramolecular and unusual intermolecular hydrogen bonds, stabilizing the compound in the crystalline state. Reaction with pyridine, its 4-substituted derivatives, and 4,4-bipyridine yields tosylates of 2-pyridinio-substituted ethyl 3-aminocrotonates.¹H NMR and IR spectra support formation of an intramolecular hydrogen bond for the E-isomer, and iodonium salts in the case of pyridinium salts for the Z-isomer. The UV spectra of the pyridinium salts show an intramolecular charge transfer band.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 770–777, June, 2000.     

Unusual pathway of alkylation of 2-(4-bromobenzylidene)-<Emphasis Type="Italic">p</Emphasis>-menthan-3-one with ethyl bromoacetate

Reaction of enolate carbanion, generated from 2-(4-bromobenzylidene)-p-menthan-3-one, with ethyl bromoacetate proceeds selectively as the O-alkylation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2420–2423, December, 2007.     

Synthesis of [2-(vinyloxy)ethyl]uracil and [2-(allyloxy)ethyl]uracil

A synthesis is reported for N¹-mono- and N¹,N³-disubstituted uracil derivatives containing a terminal carbon-carbon double bond in the side-chain. Alkylation of vinyl 2-chloroethyl ether by uracil potassium salts leads to a mixture of 1-[2-(vinyloxy)ethyl] and 1,3-di[2-(vinyloxy)ethyl] derivatives while treatment of 2,4-bis(trimethylsilyloxy)pyrimidines by vinyl 2-chloroethyl ether leads exclusively to N¹-monosubstituted products. Alkylation of cytosine by this chloroether gave 1-[2-(vinyloxy)ethyl]cytosine. The synthesis of 1-[2-(allyloxy)ethyl]uracil derivatives was carried out by treatment of uracil potassium salts by 1-(allyloxy)-2-(p-toluenesulfonyloxy)ethane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 393–397, March, 1993.     

Spectral study of the molecular structure of some 2-methylthio-6-methyl-4-alkyl- and alkylaminopyrimidines

A number of 2-methylthio-6-methyl-4-alkyl- and alkylaminopyrimidines, as well as their salts produced by the reaction with methyl p-toluenesulfonate and trifluoroacetic acid, were investigated. The quantum chemical and experimental IR and Raman spectral methods were used to determine the preferential isomeric forms of the molecules of studied compounds, whose convenient spectral markers were revealed. The starting pyrimidines and their salts were found to exist predominantly as an amino form. The salt formation proceeds via the methylation (protonation) of the N¹ atom of pyrimidine ring.     

Umwandlung von 6-Methylen-tricyclo[3.2.1.02,7]oct-3-en-8-onen in Polymethyltropyliumsalze

When dissolved in trifluoroacetic or fluorosulfonic acid, 6-methylene-tricyclo[3.2.1.0^2,7]oct-3-ene-8-one derivatives of type 2 (;scheme 1); give polymethyltropylium salts in moderate to good yields by CO-extrusion. These tropylium salts can be isolated pure as hexachloroplatinates. Thus the tricyclic compound 6 gives 1,2,4-trimethyltropylium trifluoroacetate 19 in trifluoroacetic acid (;scheme 3);. This salt in CDCl₃ is in equilibrium with its covalent cycloheptatriene (;tropilidene); form 20 , the ratio of the two forms being 1.5–2.1/1. The tropylium salt 19 is reduced by lithium aluminium hydride to a mixture of 1,2,4-trimethylcycloheptatrienes, isomeric with respect to the double bonds, which on hydride abstraction with trityl-tetrafluoroborate gives again the 1,2,4-trimethyltropylium salt 19 (;scheme 3);. From the trimethyl-substituted tricyclic compounds 7 and 8 , in trifluoroacetic acid, are obtained respectively the 1,2,4,6- and 1,2,3,4-tetramethyltropylium ions (; 22 and 24 ); (;schemes 4 and 5);. In this way the 1,2,3,5,6-pentamethyl-tropylium ion (; 26 ); was obtained from 9 (;scheme 6);. With the higher substituted tropylium trifluoroacetates in CDCl₃ the equilibrium tropylium trifluoroacetate ? trifluoroacetoxycycloheptatrienes lies well to the left. The hexamethylated tricyclic compound 10 gives a small quantity of heptamethyltropylium trifluoroacetate (; 27 ); and as the main product the C(;3);-protonated species 28 (;scheme 7);, which when treated with aqueous sodium hydrogencarbonate yielded unchanged educt 10 . - The heptamethyltropylium ion (; 27 ); was, apart from polymeric species, the only product from the treatment of starting material 10 with fluorosulfonic acid (;50%);; its salts have as yet not been isolated in their pure form, however. The mechanism for the rearrangement of the tricyclic compounds of type 2 into tropylium salts is presented for compound 6 in scheme 8: The first step is the protonation at C(;9);. Ring opening of the cyclopropane of the tertiary carbenium ion 29 gives the allylic ion 30 , which then yields the aromatic tropylium salt 19 by carbon monoxide extrusion in a linear cheletropic reaction. The smooth conversion with strong acids of the easily accessible tricyclic compounds of type 2 to the corresponding polymethylated tropylium salts, presents a new and useful method for the synthesis of the latter compounds.     

Quantum-chemical study of the equilibrium geometry and electronic structure of certain γ-pyrone derivatives

Full ab initio optimization of molecular geometry has been carried out for certain γ-pyrone derivatives: comenic, meconic, chelidonic, and kojic acids and 5-methoxy-γ-pyrone-2-carboxylic acid in the forms of free acids, their anions, sodium and calcium salts, chelate complexes with Ca²⁺, and sodium and calcium salts of the chelate complexes. The calculations were carried out by the restricted Hartree-Fock method with the 6-31G* basis using the GAMESS program. The effect of salt and complex formation on the geometric and electronic structure of the molecules under consideration has been examined. To study the effect of solvation, full geometry optimization of comenic acid and its derivatives in media with the dielectric constants ? 10 and 78.3 has been was carried out in terms of the polarizable continuum model. The energy effects of salt and complex formation has been estimated. A possible mechanism of binding of the molecules under consideration with opioid receptors has been proposed on the basis of the calculation results.     

Mechanistic study of the aldol condensation occurring in the alkaline solution of 3-hydroxy 2-oxo propranoate (β hydroxypyruvate)

With 3-bromo-2-oxopropanoate (β bromopyruvate) and its ethyl ester, the ionisation of the gemdiol of the hydrated form BrCH₂-C(OH)₂-COOR 1 initiates the elimination of bromide anion yielding 3-hydroxy-2-oxopropanoate 2 (β-hydroxypyruvate). The mechanism of the reaction was investigated essentially by polarography in aqueous solution.In neutral (and acid) media, the polarographic behaviour of 2 resembled that of other α-ketoacids: reduction at the mercury electrode yielded glycerate.In alkaline media, there was evidence of the carbanion enolate ^-O—CHC(OH)—COO^-. 3'. The overall rate constant was determined according to a kinetic law of the typer:v = k.¦2¦.¦OH^-¦; found k = 1,56 min^-1 in NaOH 0.5 N at 25°.In the pH range 10.5 to 11.5,3' existed in minor amounts and initiated a slow aldol condensation with the tautomer 3-oxo-2-hydroxypropanoate 4 (tartronate Semialdehyde) according to a kinetic law of the type v = k?.¦2¦².¦OH^-¦found k? = 211.mol^-1 min ^-1 at 25° , at pH 11.0.The aldol product was isolated as a sodium sail and its structure established by ¹³C NMR.     

Reactions of 4,5-bis(morpholin-4-yl)cyclopent-2-en-1-one with sodium salts derived from methyl dichloroacetate and ethyl (dimethyl-λ<Superscript>4</Superscript>-sulfanylidene)acetate

An attempt was made to synthesize fused cyclopropane derivatives suitable for subsequent transformation into vicinal diamino-substituted cyclohexenecarboxylic acids via reactions of 4,5-bis(morpholin-4-yl)cyclopent-2-en-1-one with sodium salts derived from methyl dichloroacetate and ethyl (dimethyl-λ⁴-sulfanylidene) acetate.     

Reaction of (ethoxycarbonylfuryl)methanephosphonates with diethyl carbonate in presence of sodium foil

Reaction of (ethoxycarbonylfuryl)methanephosphonates with diethyl carbonate in presence of sodium foil is studied. It is shown that if the acidifying group is conjugated with the carbanion center of 2-furylmethanephosphonate, addition of the carbanion to the carbonyl group of diethyl carbonate takes place to give 2-furylacetic acid derivatives in high yield. Sodium salts of these CH-acids are synthesized, isolated, and characterized. Their alkylation with alkyl bromoacetates is carried out. If ethoxycarbonyl group is not conjugated with the carbanion center, conversion of starting phosphonate and yield of adduct sharply decreases. Alkyl (2- and 4-ethoxycarbonylfur-3-yl)methanephosphonates immediately after acylation with diethyl carbonate are reduced with sodium-diethyl carbonate system to form alkyl 1-(2- and 4-ethoxycarbonylfur-3-yl)-ethanephosphonates. Formation of intermediate reduction product, the phosphorylated furylacetic aldehyde is also fixed spectroscopically. Simultaneously with the reduction dealkylation of ester group of starting phosphonates and alkyl 1-(3-furyl)ethanephosphonates takes place leading to the carboxylic acid salts. Alkyl (2-methyl-5-ethoxycarbonylfur-3-yl)methanephosphonate does not take part in condensation. It gives only the products of dealkylation under the action of sodium ethylate forming from diethyl carbonate.     

Quantum chemical modeling of superbase-catalyzed reactions of acetophenone and methyl mesityl ketone with acetylene

The mechanisms of furan formation and the competitive reaction of 1,5-diketone formation from 1-mesitylbut-2-en-1-one (1a) and 1-phenylbut-2-en-1-one (1b) were studied using the B3LYP/6-311++G**//B3LYP/6-31+G* quantum chemical approach taking into account solvation effects in terms of the IEFPCM model. The addition to 1a of the ethynide ion to form β-acetylene enolate ion (2a) occurs with the activation energy ΔG^≠ = 13.3 kcal mol^–1, while the further intramolecular O-vinylation with the closure of 2a to the dihydrofuran cycle of the dihydrofuran carbanion is the rate-determining step in the reaction pathway of substituted furan formation needing the activation energy G^≠ = 19.5 kcal mol^–1. The alternative addition of the mesitylethenolate ion to 1a to form the 1,5-diketone carbanion is associated with a higher (by 3.4 kcal mol^–1) free activation energy than that of ethynide ion addition. In contrast, in the case of 1b, the addition at the C=C bond of the phenylethenolate ion rather than of the ethynide ion to form the 1,5-diketone carbanion is more preferable, since its activation free energy is 1.5 kcal mol^–1 lower. The quantum chemical calculation results are consistent with the experimental data.     

Thiadiazole ring opening in the derivatives of 2-substituted 5-(1,2,3-thiadiazol-4-yl)-3-furoic acid under the action of bases

Transformations of the derivatives of 2-substituted 5-(1,2,3-thiadiazol-4-yl)-3-furoic acid under the action of bases has been studied. In the presence of potassium tert-butylate in THF, the studied compounds decompose with the cleavage of the thiadiazole ring, liberation of nitrogen, and formation of labile acetylene thiolates. In the presence of methyl iodide, these salts form stable 2-methylthioethynylfurans. Under the action of sodium ethylate in ethanol, thiadiazole ring of ethyl [2-methyl-5-(1,2,3-thiadiazol-4-yl)]-3-furoate is split to form the corresponding sodium acetylene thiolate. Under the action of ethanol, two molecules of this salt give bis(furyl)dithiafulvene. In the DMF–potassium carbonate system, acetylene thiolates react with primary and secondary amines giving thioamides of (4-ethoxycarbonyl-5-methylfur-2-yl)acetic acid. Treating of ethyl 2-methyland 2-N-morpholinomethyl-5-(1,2,3-thiadiazol-4-yl)-3-furoates with hydrazine hydrate leads to hydrazinolysis of the ester group and cleavage of thiadiazole ring resulting in the formation of hydrazides of 4-hydrazinocarbonylfur-2-ylacetic acid. In the case of ethyl 2-acetoxymethyl- and 2-(4-nitrophenoxy)methyl-5-(1,2,3-thiadiazol-4-yl)-3-furoates, thiadiazole ring is retained and exclusively hydrazinolysis of the ester groups is observed.     

Salts of maleic and fumaric acids with oxine: the role of isomeric acids in hydrogen‐bonding patterns

Both maleic and fumaric acid readily form adducts or complexes with other organic molecules. The 1:1 adduct formed by quinolin‐8‐ol (oxine) with maleic and fumaric acid are salts, namely 8‐hydroxyquinolinium hydrogen maleate, C₉H₈NO⁺·C₄H₃O₄⁻, (I), and 8‐hydroxyquinolinium hydrogen fumarate, C₉H₈NO⁺·C₄H₃O₄⁻, (II). The cations and anions of both salts are linked by ionic N⁺—H...O⁻ hydrogen bonds. The maleate salt crystallizes in the space group P2₁2₁2₁, while the fumarate salt crystallizes in P. The maleic and fumaric acids in their complex forms exist as semimaleate and semifumarate ions (mono‐ionized state), respectively. Classical N—H...O and O—H...O hydrogen bonds, together with short C—H...O contacts, generate an extensive hydrogen‐bonding network. The crystal structures of the maleate and fumarate salts of oxine have been elucidated to study the importance of noncovalent interactions in the aggregation and interaction patterns of biological molecules. The structures of the salts of the Z and E isomers of butenedioic acid (maleic and fumaric acid, respectively) with quinolin‐8‐ol are compared.     

3-Azido-1,2,4-triazine N-Oxides. Syntheses and structure elucidation

Several 3-azido-1,2,4-triazine 1-oxides were prepared by treating the appropriate 3-hy-drazino derivatives with nitrous acid. 3-Azido-1,2,4-triazine 2-oxide was prepared by reaching the corresponding 3-bromo derivative with either tetramethylguanidinium azide in chloroform or sodium azide in aqueous acetone. The azido derivatives which could cyclize to form the tetra-zolo isomers were proven to exist enitrely in the open chain form by a ¹³C nmr, ¹H nmr and infrared spectroscopic study.     

Mechanistic investigation and DFT calculation of the new reaction between S-methylisothiosemicarbazide and methyl acetoacetate

A study on the synthesis and mechanistical aspects of formation of 3-methyl-5-oxo-3-pyrazolin-1-carboxamide (MOPC) starting from S-methylisothiosemicarbazide hydrogen iodide and methyl acetoacetate was performed. In the alkaline aqueous solution, the intermediate methyl acetoacetate S-methylisothiosemicarbazone undergoes substitution of CH₃S^? anion by hydroxide anion, cyclization, carbanion formation, and elimination of methanol, thus yielding corresponding Na-enolate salt of pyrazol-5-one derivative. The structure of the compound obtained after protonation of the formed enolate salt was determined by means of spectroscopic techniques and single-crystal X-ray diffraction analysis. The mechanism of conversion of methyl acetoacetate S-methylisothiosemicarbazone into MOPC was investigated by means of the B3LYP functional, and it was found that the reaction is thermodynamically controlled.     

Aromatization of 3,4-dihydro-β-carboline-3-qarboxylic acid and its derivatives through a carbanion intermediate : mechanistic study and use in chemical synthesis

3,4-dlhydro-β-carboline-3-carboxylic acid , its esters and amide derivatives (AH₂) undergo complete aromatization into corresponding β-carboline derivatives (A) by basic treatment under mild conditions. This, together with the easy obtention of 3,4-dihydro-β-carboline from the parent N^αformyltryptophan derivatives constitutes an attractive possibility to obtain complex molecules containing the β-carboline ring. The mechanism of the reaction was investigated by polarography, U.V.spectrometry and polarimetry. In alcaline media, (AH₂) undergoes two successive equilibria : the first yielding a C₃ carbanion occurs with suppression of the chirality while the second yields a thermodynamically preferred C₄ carbanion which undergoes aromatization through an oxidative pathway (K'_a = 2×10^-14 at 45°C).     

Über Chalkogenolate. 206 [1]. N-Thioacetyldithiocarbamate und Ester der N-Thioacetyldithiocarbamidsäure

On Chalcogenolates. 206. N-Thioacetyl Dithiocarbamates and Esters of N-Thioacetyl Dithiocarbamic Acid Thioacetamide reacts with carbon disulfide in the presence of KH to form via the tetrabutyl ammonium salt dark yellow N-thioacetyl dithiocarbamates M[S₂C? NH? CS? CH₃], where M = K, Rb, Cs. The salts as well as the methyl and ethyl ester have been characterized by means of electron absorption, infrared, nuclear magnetic resonance (¹H and ¹³C), and mass spectra. Attempts to synthesize N-thioacetyl dithiocarbamic acid were not successful.     

Identification of esters by collisional charge inversion of their enolate ions

The collisional charge inversion and neutralization-reionization (^?NR) mass spectra of the enolate ions of m/z 115 derived from the four butyl acetates, the two propyl propionates, ethyl butyrate, ethyl isobutyrate, methyl valerate, methyl 2-methylbutyrate and methyl 3-methylbutyrate were recorded. The major primary fragmentation reactions of the unstable carbenium ion formed by charge inversion involve elimination of an alkoxy radical to form a ketene or alkylketene molecular ion and formation of an alkyl ion consisting of the R¹ group of RCOOR¹. A minor fragmentation reaction involves elimination of an alkyl radical by cleavage of a C? C bond α to the ether oxygen. The alkylketene ions fragment by β-cleavage eliminating an alkyl radical to form an olefinic acylium ion. In most cases the charge inversion mass spectra of the enolate ions allow identification of the ester.