Acylation of the 4,5- and 5,6-double bond isomers of 3-steroidal thiazolidines: The chemical stability of spiro-3-steroidal 4,5- and 5,6-double bond isomers

It has been shown that the 5,6-double bond steroidal thiazolidines can be N-acylated if there is no substituent in the 4'-position on the thiazolidine ring; substituents in the 4'-position of the thiazolidine sterically hinder acylation. On the other hand, the 4,5-double bond steroidal thiazolidine isomers decomposed on attempted acylation. The lability of these 4,5-double bond isomers was attributed to the contribution of a hyperconjugative resonance form to the structure of the 4,5-double bond isomers.     

Acylaminoacetyl derivatives of active methylene compounds. 4

Meldrum's acid has been found to be effectively acylated using the imidazolides of N-protected glycines, X-NHCH₂COOH (X = -COPh, -COMe, -Z, -Boc, -COOMe and -COOEt). The corresponding C-acylation compounds were isolated in high yields and were readily converted to the N-protected tetramic acids. It was shown by pmr spectroscopy that these acids exist as the enol tautomers in DMSO-d₆ solution, whereas in deuteriochloroform solution both the enol and keto tautomers can be observed.     

The stereochemical outcome of electrophilic addition reactions on the 5,6-double bond in the spinosyns.

The electrophilic addition of reagents to the 5,6-double bond in spinosyn A and spinosyn D systems occurred with high pi-diastereofacial selectivity. Addition occurred preferentially from the beta face of the molecule with selectivities ranging from 5:1 to better than 30:1. Various NMR properties were investigated in order to distinguish the beta and alpha isomers with the help of theoretical models of the products. These NMR properties include a (13)C gamma effect to C-11 and vicinal coupling between H-4 and H-5. To help rationalize the selectivity, computational studies on the transition states for epoxidation were calculated using density functional theory. The results indicate that beta epoxidation is favored and that the geometries of the transition structures are consistent with torsional steering being the source of the selectivity.     

Rhenium-catalyzed insertion of terminal acetylenes into a C-H bond of active methylene compounds

[reaction: see text] A rhenium complex, [ReBr(CO)(3)(thf)](2), catalyzed the intermolecular reactions of 1,3-dicarbonyl compounds with terminal acetylenes and gave the corresponding alkenyl derivatives in excellent yields. These reactions could apply to an intramolecular version and gave the corresponding cyclic compounds quantitatively.     

Search for a simpler synthetic model system for intramolecular 1,3-dipolar cycloaddition to the 5,6-double bond of a pyrimidine nucleoside

In search for a simpler model system for the study of intramolecular thermal reactions between the base and 5'-functionalized sugar moiety in nucleosides, 1-(3-azidopropyl)uracil (2), 1-(4-azidobutyl) pyrimidines (12 and 13) and 1-(5-azidopentyl)-uracil (14) was synthesized through the corresponding ω-benzoyloxy-(6,7 and 8) and ω-hydroxyalkyl-pyrimidines (9,10 and 11). Heating 2 gave 1,N⁶-trimethylene-6-aminouracil (4), while heating 12 and 13 gave N¹-C₆ cleaved addition products. 15 and 16, respectively. 15 was regiospecifically transformed to 1,2,3-triazole derivatives, 17,18 and 19. Heating 1-(4-azidobutyl)-5-bromouracil (20) yielded 3,9-tetramethylene-8-azaxanthine (22). 9 with NBA gave 1,0⁶-tetramethylene-5-bromo-6-hydroxy-5,6-dihydrouracil (24) and the 5-brominated analog of 9 (25). The 4-functionalized butyl side chain proved to serve as a substitute for the 5'-functionalized sugar moiety in pyrimidine ribonucleosides.     

Flow-injection methods for the determination of uracil derivatives with voltammetric detection

Flow-injection methods are described for the determination of 18 uracil derivatives and related compounds, by means of differential-pulse amperometry (d.p.a.) or differential-pulse cathodic stripping voltammetry (d.p.c.s.v.). The carrier stream is a borax/KNO₃/HNO₃ (of NaOH) solution containing 0.001% (v/v) Triton X-100. This surfactant displaces the oxygen reduction peak to such negative potentials that deaeration is unnecessary for detection of compounds having peak potentials in the range 180–70 mV (vs. Ag/AgCI) at pH 7.6. At the hanging mercury drop electrode, the uracil derivative is deposited from the flowing sample at a fixed potential more positive than the relevant peak potential and stripped under stopped-flow or slow-flow conditions. In the amperometric mode, a constant potential also more positive than the relevant peak potential is applied to the dropping mercury electrode and the resulting peak is measured under flow conditions. Linear calibration graphs were found for most of the compounds at 10^?6–10^?7 M by d.p.a, and about one order of magnitude lower by d.p.c.s.v.. The limit of determination for 5-iodouracil was 5×10^?9 M (ca. 1.2 ng ml^?1). Separation is needed for applications to blood or urine. Simple deproteination followed by high-performance liquid chromatography with a reversed-phase column proved satisfactory. Separations of various uracil derivatives, and of 5-fluorouracil, uric acid and 5-fluorodeoxyuridine, are described; spectrophotometric and amperometric detectors were used sequentially to check performance.     

Acylaminoacetyl derivatives of active methylene compounds. 3 . C-Acylation Reactions via the Hippuric Acid Azlactone

The C-acylation reactions of the active methylene compounds, methyl cyanoacetate and Meldrum's acid, with hippuric acid, using the DCC activation and the mixed anhydride conditions, are shown to proceed through initial formation of 2-phenyl-5(4H)-oxazolone, the hippuric acid azlactone. The conditions of these reactions using the azlactone as the acylating agent were investigated and discussed.     

13C NMR spectroscopy of 4,5- and 5,6-double bond isomers of spiro-3-steroidal ketone derivatives : The determination of the structures of steroidal thiazolidines

The thiazolidine isomers obtained upon the reaction of aminoethanethiols with α,β-unsaturated steroidal ketones were found to be double bond positional isomers based on their optical rotations and ¹H and ¹³C NMR spectra. The ¹³C NMR spectra of analogous ketals, hemithioketals and a thioketal of steroidal ketones were also reported, and ¹³C NMR spectroscopy was shown to be a convenient method of assigning the position of the double bond in the double bond isomers for all four of these derivatives. Finally, ¹³C NMR spectroscopy was found to be useful in determining that thiazolidine formation was stereospecific to give only one C-3-isomer.     

Reaction of indol-3(2H)-one derivatives with some active methylene compounds

The reaction of substituted (Z)- and (E)-2-arylmethylideneindolin-3(2H)-ones with malononitrile gave the Micheal addition products which could be cyclised to the corresponding pyrano[3,2-b]indole. Larger molecules such as cyanoacetic acid and ethyl cyanoacetate failed to react.     

有机磷化合物的研究IX.某些具有活泼亚甲基化合物的碳磷酰化反应

The formation of P -- C bond is one of the important problems in synthetic organophosphorous chemistry. This paper describes the study of the formation of P -- C linkage via phosphorylation of carbon atom containing active hydrogen. p-Substituted phenylacetonitrile possessing an active methylene group undergoes stepwise C -- phosphorylation smoothly with diethyl phosphoryl chloride in the presence of naphthalene-sodium. Phosphonyl chloride reacts analogously. Being a deprotonizing agent naphthalene-sodium is distinguished by its availability, effectiveness and mild reaction conditions. The presence of an electron-withdrawing group in the benzene ring reduces the yield of phosphorylation seriously. The chemical shift of ^3^1P NMR of the resulted α-cyano-benzylphosphonates (1) correlates linearly with the Hammett \s\ constants of the substituents. As indicated by ^1H NMR studies the protons in the ester ethyl groups are magnetically nonequivalent. Compound 1 can be alkylated with alkyl halide or condensed with aromatic aldehyde by Hornor-Wittig type reaction due to the presence of active hydrogen atom. The structure-reactivity studies of diethyl phosphoryl chloride on reacting with various β- and β-diketones and β-keto esters (5) as regiospecific reaction were reported. The influences of metal ions in the enolates on the reactivity of the latter were examined and discussed. Only vinyl phosphates with predominantly Z configuration have been isolated exclusively. The C atom with an active hydrogen in the β-diketones investigated is inert to phosphorylation. These experimental results are well supported by reaction selectivity in terms of Eqo/Ecoc based on EHMO calculation.     

Unusual modification methods for the ureido ligand of lanthanocene derivatives

(C5H5)2Ln[OC(PzMe2)=NPh](THF) (Ln = Dy (1a), Er (1b), Yb (1c), Y (1d)) were prepared in good yields by the PhNCO insertion into the Ln-N bond of (C(5)H(5))(2)Ln(PzMe(2))(THF) (PzMe(2) = 3,5-dimethylpyrazolate) in THF at room temperature. Treatment of with p-aminothiophenol in THF at room temperature gives unusual ligand-based substitution derivatives {(C5H5)2Ln[mu-eta1:eta3-OC(p-H2NC6H4S)NPh]}2.2THF (Ln = Dy (2a), Er (2b), Yb (2c), Y (2d)), while reaction of 1c with o-aminothiophenol instead of p-aminothiophenol allows the occurrence of a tandem substitution/cyclization/elimination to form unexpected benzothiazole-2-oxide complex [(C5H5)2Yb(mu-eta1:eta3-OSNC7H4)]2 (3c), representing a novel modification method for non-cyclopentadienyl ligands of lanthanocene derivatives. However, complex does not react with benzyl thiol, indicating that the nature of thiols has a profound influence on the substitution reaction. All complexes were characterized by elemental analysis and spectroscopic properties. The X-ray diffraction analysis reveals that and are solvated monomeric structures, while and are centrosymmetric dimeric ones with an unusual intermolecular hydrogen bond interaction involving THF.     

Reaction of 1,3,4-thiadiazolo and 1,3,4-triazolo[3,2-c]quinazoline derivatives with active methylene compounds

Fused quinazoline derivatives 1 and 4 react with active methylene compounds and depending on the annelated five-membered ring, two types of transformations have been observed. The 1,3,4-thiadiazolo[3,2-c]quinazoline 1 , underwent the five-membered ring opening reaction to afford the 3,4-dihydroquinazolines 2 in good yields, whereas the 1,3,4-triazolo[3,2-c]quinazoline 4 underwent nucleophilic attack at 2-position of the quinazoline ring to yield the corresponding 1,2,4-triazoles 5 .     

Quantum chemical study of mechanism for insertion of singlet methylene into C-C1 bond

Conclusions Quantum chemical calculation by the expanded Huckel method revealed that the mechanism for the insertion of singlet methylene into the C-C1 bond of methyl chloride consists in the electrophilic attack by methylene on the C-Cl bond, with a subsequent synchronous transfer of the chlorine atom to the methyl and the formation of ethyl chloride; here the vacant p-orbital of methylene does not react with the unshared pairs of the chlorine atom.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2622–2625, November, 1973.     

Studies on organophosphorous compounds: IX. C-Phosphorylation of compounds bearing an active methylene group

The behaviour of carbanions of para-substituted benzylcyanides and ambident enolates toward phosphorylation has been examined. In the former case the C-phosphorylation proceeded smoothly, while the ambident enolate ions derived either from β-diketones or from β-ketoesters gave exclusively regiospecific O-phosphorylation products on reaction with diethyl phosphoryl chloride. The experimental results are well supported by reaction selectivity in terms of E_qo/E_C.OC/ based on EHMO calculation.     

Acylaminoacetyl derivatives of active methylene compounds. 1. The cyclization of the benzoylaminoacetyl derivatives to α-substituted tetramic acids

Hippuric acid was converted to α-Y-substituted tetramic acids (Y = -CN, -CO₂R and -COCH₃) according to the following general scheme of reactions: a) preparation of the hippuric acid chloride or of its p-nitrophenyl ester; b) C-acylation of an active methylene compound Y-CH₂-CO₂R using the acid chloride or the active ester; and c) intramolecular condensation of the C-acylation compound to an α-Y-substituted tetramic acid. The conditions of the C-acylation reaction and the structure and reactivity of the benzoylaminoacetyl derivatives were investigated.     

A new synthesis of α-amino acids—III: Amidoalkylation of active methylene compounds with glyoxylic acid derivatives

The synthesis of N-acyl derivatives of γ - keto - α - amino acids (3, 4, 5) by the amidoalkylation of 1,3-dicarbonyl compounds with glyoxylic acid-amide adducts (1, 2) is described. The γ - keto - α - amino acid derivatives (4, 5) were further converted to the corresponding butenolides (6, 7) and to pyrazolylglycine (12).     

Monolithic methacrylate polymeric sorbents: Development of methods for chemical modification of the surface for the subsequent bioaffine functionalization

Copolymers containing aldehyde, succinimidyl carbonate, and imidazolecarbamate groups were prepared by polymer-analogous transformations of epoxy groups of a macroporous monolithic polymeric support derived from glycidyl methacrylate and ethylene glycol dimethacyrlate. The effect of certain parameters on the course of the copolymer modification and immobilization of a protein on the surface of the polymeric support was studied. The possibility of using the matrices obtained for development of biorecognizing systems was examined.     

Imidazolium salts as phase transfer catalysts for the dialkylation and cycloalkylation of active methylene compounds

The dialkylation and cycloalkylation reactions of active methylene compounds in the presence of readily available imidazolium salts (ionic liquids) as phase transfer catalysts were performed to afford the respective dialkylated or cycloalkylated products. This method is very efficient for the synthesis of 1,1-disubstituted derivatives and cyclopropane and cyclopentane ring systems in a facile manner.     

Expeditious reaction of ninhydrin with active methylene compounds on montmorillonite K10 clay

Abstract  Ninhydrin reacted expeditiously with thirteen active methylene compounds on montmorillonite K10 clay at room temperature to furnish, in 5 min, a Knoevenagel condensate in one case, aldols in six cases, aldol-derived cyclic hemiketals in three cases, and interesting products in the remaining three cases. Almost identical results were obtained, but faster, when the reactions were carried out in water on steam-bath. The structures of two novel products were also confirmed by single-crystal X-ray diffraction analysis. Graphical abstract