Research on pyrazolidine

4-Alkyl-4-(1-cycloalkenyl)-1,2-diphenyl-3,5-dioxopyrazolidines were obtained by the reaction of 4-cycloalkylidene-1,2-diphenyl-3,5-dioxopyrazolidines with alkyl halides.See [1] for communication 23.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 254–256, February, 1979.     

Studies in pyrazolidine chemistry

The Lewis acidity of 4-ylidene-3,5-dioxopyrazolidines decreases with increasing electron-donor capacity of the substituents in the para position of the 4-benzylidene residue and in the -position of the exocyclic double bond. An analogous effect is found for the substituents in the 4-benzylidene residue on the NH-acidity of 1-phenyl-4-benzylidene-3,5-dioxopyrazolidines. The observed effect is analogous to their influence on the halfwave potential in the polarographic reduction on a dropping mercury electrode.For Communication 26, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 83–85, January, 1989.     

Pyrazolidine chemistry

In contrast to 4-benzylidene-1,2-diphenyl-3,5-dioxopyrazolidine and its aromatic and heterocyclic analogs, 4-ethylidene derivatives and their cyclic analogs are hydrogenated at the exocyclic double bond not only in neutral ethanol but also in ethanol in the presence of alkali. The UV spectra of the starting compounds and hydrogenation products in ethanol at various pH values were examined, and the possible reasons for the anomalous hydrogenation of the 4-ethylidene derivatives are discussed.See [1] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 657–661, May, 1971.     

Research in the chemistry of pyrazolidine XXIII. Study of the reaction of 3,5-dioxopyrazolidines with β-nitrostyrene

Products of Michael condensation containing a 1-phenyl-2-nitroethyl residue in the 4 position of the heteroring are formed in high yields in the reaction of equimolar amounts of 4-methyl-,4-ethyl-, 4-isopropyl-, 4-butyl-, 4-isoamyl-, and 4-phenyl-1, 2-diphenyl-3,5-dioxopyrazolidines and 1,2-diphenyl-3,5-dioxopyrazolidine with -nitrostyrene under basic catalysis conditions. 1,2-Diphenyl-3,5-dioxopyrazolidine adds two equivalents of -nitrostyrene when a twofold excess of the latter is present.See [1] for communication XXII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 963–964, July, 1978.     

Unusual amino acids. 5. Synthesis of 3,5-dioxopyrazolidine derivatives

Monohydrazides of 2-R-4-methyl-4-cyclohexene-1,1-dicarboxylic acids react with trifluoroacetic acid anhydride to give 4-substituted 3,5-dioxopyrazolidines, with phosphorus trichloride to give 4-(2-R-5-chloro-4-methylcyclohexane)-3,5-dioxopyrazolidines, and with acetic anhydride to give 4-(2-R-4-methyl-4-cyclohexene)-3,5-diacetoxypryazoles.For Communication 4, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 903–907, July, 2000.     

Research in the chemistry of pyrazolidine

The rate of hydrogenolysis of 3,5-dioxopyrazolidines at the N-N bond is determined by the number, position, and nature of the substituents in the heteroring. The introduction of a phenyl group into the 1 and 2 positions increases the rate of hydrogenation, while a phenyl group in the 4 position lowers it. On the other hand, an alkyl substituent in the 1 and 2 positions lowers the rate of hydrogenation, while an alkyl substituent in the 4 position increases it. It is assumed that the effect of substituents is a consequence of an increase or decrease in the adsorption of a molecule by the -dicarbonyl or hydrazine fragments; this is in agreement with the results of calculation of the charges on the heteroring atoms. The hydrogenation of 4alkyl-1, 2-diphenyl-3,5-dioxopyrazolidines is limited by their activation, while the hydrogenation of the 4-phenyl derivative is limited by the activation of hydrogen.See [1] for communication XIX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 781–787, June, 1973.     

Synthesis of sterically hindered phenol-containing phosphorylated isatin derivatives

Addition of isatin to the exocyclic double bond of dimethyl (3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)methylphosphonate gave dimethyl (3,5-di-tert-butyl-4-hydroxyphenyl)(2,3-dioxo-2,3-dihydro-1H-indol-1-yl)methylphosphonate. Its subsequent functionalization in reactions with thiosemicarbazide and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionohydrazide yielded isatin derivatives containing several pharmacophoric fragments.     

Einfluss der A-spannung auf die stereochemie von oximen und semicarbazonen

In piperidone-(4)-oximes, the A^1,3 strain between the substituent at the exocyclic double bond and a Me group causes the sole formation of anti-isomers. A change of the ring conformation avoids the A^1,3 strain in 1-methyl-2,6-diphenyl-3,5-dimethyl-piperidone-(4)-oxime. trans-Configuration of the Me substituents at C-3 and C-5 can be shown in a correspondingly substituted semicarbazone; in this example, the A^1,3 strain is avoided by epimerization. This semicarbazone can be transformed into the 3,5-trans-disubstituted piperidone by cerium(IV) oxidation.     

Rotation about the exocyclic carbon-carbon double bond of amino dienes of the indolo[2,3-a]-and benzo[a]quinolizidine series

Quinolizidines containing an exocyclic double bond at C-2 (1,2) give on mild oxidation the amino dienes (3,4), as mixtures of geometric isomers with respect to the exocyclic double bond. The free enthalpy of activation for the rotation about the double bond has been estimated by NMR.     

Sodium dithionite initiated addition of CF2Br2 to β-pinene and reactions of the adduct: Synthesis and the reactivity of new 1,1-difluorodienes

Sodium dithionite effectively promotes the addition of dibromodifluoromethane to the exocyclic double bond of β-pinene. The reaction proceeded in a MeCN/H₂O system to give almost quantitatively an adduct, 1-(2-bromo-2,2-difluoroethyl)-4-(2-bromoisopropyl)-cyclohexene, as the sole product. On treatment of the adduct with 2,2,6,6-tetramethylpiperidine elimination of HBr only from the (CH₃)₂CHBr group occurred to give a mixture of regioisomeric dienes, while treatment with 50% KOH under phase transfer catalysis conditions or with K₂CO₃ in DMF resulted in total dehydrobromination to give trienes possessing an exocyclic CHCF₂ group. Surprisingly, the main course of the reactions of the adduct with DBU (1,8-diazabicyclo[5.4.0]undece-7-ene) and also with t-BuOK in THF was elimination of HBr only from the CH₂CF₂Br group to afford 1-(2,2-difluorovinyl)-4-(2-bromoisopropyl)cyclohexene as the main product. Catalytic hydrogenation of the adduct followed by treatment with DBU afforded a conjugated diene, 1-(2,2-difluorovinyl)-4-isopropylcyclohexene. Compounds bearing the CHCF₂ group are new 1,1-difluorodienes which readily reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to give cycloadducts, derivatives of triazolo[1,2-α]cinnoline.     

Photocycloaddition Reactions of 2‐(Alk‐3‐en‐1‐ynyl)cyclohex‐2‐enones

The newly synthesized 2‐(alk‐3‐en‐1‐ynyl)cyclohex‐2‐enones 4 undergo photodimerization (chemo‐ and regio‐)selectively at the exocyclic C?C bond to give diastereoisomeric mixtures of 1,2‐dialkynyl‐1,2‐dimethylcyclobutanes. On irradiation of 4 in the presence of 2‐chloroacrylonitrile, cyclobutane formation occurs again (chemo‐ and regio‐)selectively at the exocyclic C?C bond to afford diastereoisomeric mixtures of 2‐alkynyl‐1‐chloro‐2‐methylcyclobutanecarbonitriles. Similarly, compounds 4 undergo photoaddition to 2,3‐dimethylbuta‐1,3‐diene exclusively at the exocyclic C?C bond to afford mixtures of [2+2] and [4+2] cycloadducts.     

Methyl (E)-2-(2-phenylcyclopropylidene)acetate: Synthesis, isomerization, and reaction with 1,3-diphenyl-2-benzofuran

Treatment of 3-methyl-2-phenylcycloprop-2-ene-1-carboxylic acid with potassium tert-butoxide induced its isomerization into trans-2-methylidene-3-phenylcyclopropane-1-carboxylic acid which was converted into methyl ester, and heating of the latter for 1 h in toluene gave methyl (E)-2-(2-phenylcyclopropylidene)acetate. Thermal isomerization of methyl (E)-2-(2-phenylcyclopropylidene)acetate on prolonged heating in toluene afforded 5-methoxy-3-methyl-2-phenylfuran, and the reaction with 1,3-diphenyl-2-benzofuran resulted in [4 + 2]-cycloaddition at the exocyclic double bond.     

Synthesis of novel phosphorus-containing sterically hindered phenols by the reaction of diphenyl (3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)methylphosphonate with phenols

Diphenyl (3,5-di-tert-butyl-4-hydroxybenzyl)phosphonate was oxidized to the corresponding methylidenequinonoid derivative. The addition of phenols to the exocyclic double bond of this compound gave phosphonates with two phenol moieties.     

Polarity and structure of 2-(1-methylbenzimidazol-2-yl)-1-phenyl- and -1,2-diphenyl-1-nitroethenes

Polarity of 2-(1-methylbenzimidazol-2-yl)-1-phenyl- and -1,2-diphenyl-1-nitroethenes was determined and their structure was studied using electronic and ¹H, ¹³C NMR spectroscopy, dipole moments measuring, XRD analysis, and quantum-chemical calculations. It was shown that the 2-(1-methylbenzimidazol-2-yl)-1-nitro-1-phenylethene has Z-configuration both in crystal and solution. The nitro group and benzimidazole substituent in its molecule are removed from the plane of the double bond. For 1,2-diphenyl-1-nitroethene E-structure is typical.     

Molecular and crystal structure of 3,3-dimethyl-5-(2-naphthyl)-1-(4-nitrophenyl)-3,5a-dihydro-1H-azireno[1,2-c]imidazole

An X-ray study of 3,3-dimethyl-5-(2-naphthyl)-1-(4-nitrophenyl)-3,5a-dihydro-1H-azireno[1,2-c]imidazole revealed that the pyrazoline cycle has an envelope conformation. The endocyclic C=N double bond is slightly twisted. Quantum chemical calculations showed that this ring conformation is due to intramolecular interactions and is typical for substituted bicyclic aziridines.     

Polarographic behavior of 4-aryl-2-(1,2-diphenyl-2-oxoethylidenehydrazino)-4-oxo-2-butenoic acids

Polarographic reduction of 4-aryl-2-(1,2-diphenyl-2-oxoethylidenehydrazino)-4-oxo-2-butenoic acids in 2-propanol-water solutions proceeds with the formation of two or three irreversible cathode waves and leads to 4-aryl-2-(1,2-diphenyl-2-hydroxyethylhydrazino)-4-hydroxybutanoic acids. The latter suffer hydrolysis with the rupture of the C²-NH bond and the formation of 4-aryl-2,4-dihydroxybutanoic acids.     

Reactions of γ-Sultines with Electrophilic Reagents. 3. Chlorination of 3,5-Diaryl-1,2-oxathiolane 2-Oxides

The influence of the nature of the aryl substituents and the reaction conditions for the chlorination of 3,5-diphenyl-1,2-oxathiolane 2-oxide and 3,5-bis(4-methoxyphenyl)-1,2-oxathiolane 2-oxide have been studied. Possible mechanisms for the chlorination of -sultines are discussed.     

Preparation of 4-bromo-1-hydroxypyrazole 2-oxides by nitrosation of α-bromo-α,β-unsaturated ketoximes

Nitrosation of the oximes of 3-bromo-3-penten-2-one, 3-bromo-4-phenyl-3-buten-2-one, and 2-bromo-1,3-diphenyl-2-propen-1-one using sodium nitrite in acetic acid gave low yields of 4-pyrazolone 1,2-dioxides. Nitrosation using butyl nitrite in the presence of copper(II) sulfate and pyridine in aqueous ethanol produced insoluble copper complexes from which 3,5-dimethyl-, 3-methyl-5-phenyl-, and 3,5-diphenyl-4-bromo-1-hydroxypyrazole 2-oxides could be liberated by treatment with dilute potassium hydroxide, filtration, and acidification of the filtrate. High yields were obtained with the first two oximes, but, presumably due to unfavorable stereochemistry of the oxime, the diphenyl derivative gave a lower yield of the complex, accompanied by 4-bromo- and 4-nitro-3,5-diphenylisoxazole and 4-oximino-3,5-diphenyl-4,5-dihydroisoxazole.     

Crystal and molecular structure of 1-ferrocenyl-r-3,t-5-diphenyl-c-4-(1-ferrocenylvinyl)-1-cyclohexene

X-ray diffraction has been used to establish the crystal and molecular structure of one diastereoisomer of 1-ferrocenyl-3,5-diphenyl-4-(1-ferrocenylvinyl)-1-cyclohexene. This diastereoisomer, formed in the greatest amounts in the protoncatalyzed cyclodimerization of 1-phenyl-3-ferrocenyl-1,3-butadiene, is shown to have the r-3, c-4, t-5 configuration of the exocyclic substituents.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1216–1220, May, 1991.     

Oxidation of cis- and trans-3,5-di-tert-butyl-3,5-diphenyl-1,2,4-trithiolanes: isolation and properties of the 1-oxides and the 1,2-dioxides

Oxidation of trans-3,5-di-tert-butyl-3,5-diphenyl-1,2,4-trithiolane with dimethyldioxirane (DMD) or m-chloroperbenzoic acid (MCPBA) gave two stereoisomeric (1S*,3S*,5S*)- and (1R*,3S*,5S*)-1-oxides (16 and 17, respectively). Oxidation of 16 with DMD gave the (1S*,2R*,3S*,5S*)-1,2-dioxide (18) and the 1,1-dioxide 19, and that of 17 yielded the (1R*,2R*,3S*,5S*)-1,2-dioxide (20) mainly along with 18 and 19. The structures of the 1,2-dioxides 18 and 20 were determined by X-ray crystallography. 1,2-Dioxides 18 and 20 isomerized to each other in solution, and the equilibrium constant K (20/18) is 19 in CDCl(3) at 295 K. The kinetic study suggested a biradical mechanism for the isomerization. Isomerization of 16 and 17 to cis-3,5-di-tert-butyl-1,2,4-trithiolane 1-oxides by treatment with Me(3)O(+)BF(4)(-) is also described.