Reactions of Substituted 2,3,7-Triazabicyclo[3.3.0]oct-3-ene-4-carboxylic Acid Esters with Halogens

Substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acid esters react with chlorine and bromine to give the corresponding 4-halo-2,3,7-triazabicyclo[3.3.0]oct-2-ene-4-carboxylates. Heating of the latter to 120°C under reduced pressure leads to elimination of nitrogen molecule and formation of 6-halo-3-azabicyclo[3.1.0]hexane-6-carboxylates.     

Thermolysis of the esters of substituted 3,7-triazabicydo[3.3.0]oct-3-ene-4-carboxylic acids

Heating to 190–200‡C of the esters of substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acids afforded esters of 3-azabicyclo[3.1.0]hexane-6-carboxylic acids as a mixture of exo and endo isomers. The reaction carried out in chlorobenzene at 130‡C in the presence of copper stearate yielded only exo isomers. The study was carried out under financial support of the Russian Ministry of Education (grant no. 97-0-9.4-118).     

Reaction of Substituted Methyl 2,3,7-Triazabicyclo[3.3.0]oct-3-ene-4-carboxylates and 1,2,7-Triazaspiro[4.4]non-2-ene-3-carboxylates with Iodinating Agents

Substituted methyl 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylates and 1,2,7-triazaspiro[4.4]non-2-ene-3-carboxylates react with N-iodosuccinimide (or the system iodine-silver trifluoroacetate) to give, respectively, methyl 6-iodo-3-azabicyclo[3.1.0]hexane-6-carboxylates or methyl 1-iodo-4,6-dioxo-5-azaspiro[2.4]heptane-1-carboxylates as mixtures of exo and endo isomers.     

Reactions of Substituted 2,3,7-Triazabicyclo[3.3.0]oct-2-enes and 1,2,7-Triazaspiro[4.4]non-1-enes with Halogens

Halogenation of 1-substituted 7-aryl-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-diones gives different products, depending on the substituent in position 1 (R¹): when R¹ = Ar, 6-chloro-3-azabicyclo[3.1.0]hexanes are formed, while compounds with R¹ = H or Me give rise to 2- or 4-chloro-2,3,7-triazabicyclo[3.3.0]oct-2-ene-6,8-diones whose thermolysis leads to formation of the corresponding 6-chloro-3-azabicyclo[3.1.0]hexanes. Chlorination of 7-aryl-1,2,7-triazaspiro[4.4]non-1-ene-6,8-diones yields 3-chloro-1,2,7-triazaspiro[4.4]non-1-ene-6,8-diones, and thermolysis of the latter affords 1-chloro-5-azaspiro[2.4]heptanes.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 1, 2005, pp. 78–88.Original Russian Text Copyright © 2005 by Molchanov, Stepakov, Kostikov.     

Reaction of Substituted 6,8-Dioxo-2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylates and 6,8-Dioxo-1,2,7-triazaspiro[4.4]non-2-ene-3-carboxylates with N-Fluoropyridinium Tetrafluoroborate

Substituted 6,8-dioxo-2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylates react with N-fluoropyridinium tetrafluoroborate to give mixtures of exo and endo isomers of 6-fluoro-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylates. Analogous reaction of 6,8-dioxo-1,2,7-triazaspiro[4.4]non-2-ene-3-carboxylates results in formation of syn,anti-isomeric 1-fluoro-4,6-dioxo-5-azaspiro[2.4]heptane-1-carboxylates.     

Reduction of 7-aryl-6,8-dioxo-2-oxa-3,7-diazabicyclo[3.3.0]oct-3-ene-4-carboxylic and 7-aryl-6,8-dioxo-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carboxylic acid esters

Ethyl 7-aryl-6,8-dioxo-2-oxa-3,7-diazabicyclo[3.3.0]oct-3-ene-4-carboxylates and ethyl 7-aryl-6,8-dioxo-1-oxa-2,7-diazaspiro[4.4]non-2-ene-3-carboxylates were selectively reduced with sodium tetrahydridoborate at the carbonyl group in the β-position with respect to the oxygen atom in the isoxazole ring.     

Synthesis and transformations of di-endo-3-aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic acid derivatives

all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all-endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of b-amino ester 4 resulted in tricyclic pyrimidinones 15 and 16. The structures, stereochemistry and relative configurations of the synthesized compounds were determined by IR and NMR.     

Reactions of Aliphatic Diazo Compounds: IV. Reaction of Diphenyldiazomethane with Substituted Imides of Maleic and Itaconic Acids

Diphenyldiazomethane regioselectively adds to 2-R-substituted maleimides to yield 1-pyrazoline derivatives, 1-R-7-aryl-6,8-dioxo-4,4-diphenyl-2,3,7-triazabicyclo[3.3.0]oct-2-enes that on heating liberate nitrogen to afford substituted 3-azabicyclo[3.1.0]hexanes. To the N-arylsubstituted imides of itaconic acid the diphenyldiazomethane adds to furnish 5-aryl-4,6-dioxo-1,1-diphenyl-5-azaspiro[2.4]heptanes.     

A new synthetic route to substituted 1-fluoro-1-cyclopropanecarboxylates

Substituted 6-fluoro-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-carboxylates were obtained as a mixture of the exo- and endo-isomers by reaction of substituted 6,8-dioxo-2,3,7-triazabicyclo[3.3.0]oct-3-en-4-carboxylates with N-fluoropyridinium tetrafluoroborate.     

Structure elucidation and synthesis of (2s)-4-oxo-1-azabicyclo[3.3.0]octa-5,7-diehe-2-carboxylic acid,a new metabolite isolated ercm stheptomyces oliyacbjs

The structure of a new metabolite isolated from $\text{Streptomyces}$$\text{olivaceus}$ has been shown to be (2S)-4-oxo-1-azabicyclo[3.3.0]octa-5,7-diene-2-carboxylic acid by means of its spectroscopic properties and total synthesis.     

Acetylenic Esters of Polychlorobicyclo[2.2.1]hept-2-ene-5-carboxylic Acids

Acetylenic esters of polychlorobicyclo[2.2.1]hept-2-ene-5-carboxylic acids were prepared from the corresponding acid chlorides and acetylenic alcohols.     

Synthesis of 3-(4-heteroaryl-phenyl)-8-oxabicyclo[3.2.1]octane-2-carboxylic acid methyl esters

Cross coupling protocols were applied for the synthesis of 3-(4-heteroaryl-phenyl)-8-oxabicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl esters. Stille conditions produced the corresponding products in reasonable yields. Samarium iodide reduction of the resulting coupling products produced the 2β-carbomethoxy-3α-aryl-8-oxabicyclo[3.2.1]octane diastereoisomers as the major, and the 2β-carbomethoxy-3β-aryl-8-oxabicyclo[3.2.1]octane diastereoisomer as the minor products. Both diastereomers manifested inhibition of the dopamine (DAT) and serotonin (SERT) transporters, with some selectivity for SERT inhibition.     

Synthesis and mesomorphic properties of some derivatives of 2-methylcyclohex-2-ene-4-one-1-carboxylic and cis-2,6-dimethyl cyclohex-2-ene-4-one-1 -carboxylic acids

Mesomorphic derivatives prepared from ethyl esters of 2-methylcyclohex-2-ene-4-one-1-carboxylic and cis-2,6-dimethylcyclohex-2-ene-4-one-1-carboxylic acids have been synthesized. It has been shown that the compounds obtained are characterized by a lower nematic—isotropic transition temperature (10-20°C) and a considerably narrower nematic range in comparison with the analogous derivatives of 4-alkylcyclohex-3-ene-carboxylic and trans-4-alkylcyclohexane-carboxylic acid.     

Reaction of 1,3-thiazolidine-4-carboxylic and 1,4-tetrahydro-thiazine-3-carboxylic acid esters with isocyanates and isothiocyanates and structures of the reaction products

7-Thia-1,3-diazabicyclo[3.3.0]octane-2,4-diones and 7-thia-1,3-diazabicyclo[4.3.0]-nonane-2, 4-diones, as well as their thio analogs, were obtained by the reaction of (S)-1,3-thiazolidine-4-carboxylic and 1,4-tetrahydrothiazine-3-carboxylic acid esters with isocyanates and isothiocyanates. Intermediate reaction products, viz., heterocyclic derivatives of urea, were isolated. The three-dimensional structures of the 3-methyl-4-oxo-7-thia-1,3-diazabicyclo[3.3.0]octane-2-thione and 3-methyl-4-oxo-7-thia-1, 3-diazabicyclo[4.3.0]nonane-2-thione molecules were determined by x-ray diffraction analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1327–1332, October, 1985.     

Conformational analysis in the reversible intramolecular [2+2] photocycloaddition of diphenylbicyclo[4.2.0]oct-3-ene-2,5-diones

An irradiation of diphenylbicyclo[4.2.0]oct-3-ene-2,5-diones bearing variously substituted Me groups resulted in the reversible intramolecular [2+2] cycloaddition between the excited enedione CC double bond and the facing endo-phenyl ring to exclusively give pentacyclotetradeca-10,12-diene-2,7-diones. The equilibrated product ratios were much dependent on the substitution pattern of the Me-groups as well as the irradiated wavelength. The regiochemistry of these photoadditions was elucidated on the basis of the restricted conformation of the starting enediones.     

Substituent effects on the acidity of weak acids. 1. Bicyclo[2.2.2]octane-1-carboxylic acids and bicyclo[1.1.1]pentane-1-carboxylic acids

The acidities of 3- and 4-substituted bicyclooctane-1-carboxylic acids and 3-substituted bicyclo[1.1.1]pentane-1-carboxylic acids have been calculated at the MP2/6-311++G** theoretical level. There is good agreement between the calculated and observed gas-phase acidities. The acidities of the 4-substituted bicyclooctane acids were found to be linearly dependent on the C-X bond dipoles, as expected from a field effect. The substituents had a negligible effect on the electron density at C1. The difference in acidity between 4-chlorobicyclo[2.2.2]octane-1-carboxylic acid and the parent acid (6.2 kcal/mol) is reproduced by the Kirkwood-Westheimer treatment of substituent effects on acidity, but only if the bicyclooctane ring is given an effective dielectric constant of unity. The acidities of the 3-substituted bicyclooctane acids are linearly related to the corresponding 4-substituted acids with a slope of 0.9. The acidities of the 3-substituted bicyclo[1.1.1]pentane-1-carboxylic acids are linearly related to the C-X bond dipoles for this ring system (which are different than those for the bicyclooctanes), and they are also linearly related to the acidity of the 4-substituted bicyclo[2.2.2]octanecarboxylic acids with a slope of 1.34. The larger slope is due to the smaller bridgehead-bridgehead distance in the bicyclopentane ring than in bicyclo[2.2.2]octane.     

Synthesis of methyl esters of 5-amino-4-(substituted amino)-2-methylthio-7H-pyrrolo[2,3d]-pyrimidine-6-carboxylic acids

The optimum route for the synthesis of methyl esters of N-[(4-substituted amino)-5-cyano-2-methylthiopyrimidin-6-yl]amino acids (which are starting materials for preparing the methyl esters of the corresponding 5-amino-4-(substituted amino)pyrrolo[2,3-d]pyrimidine-6-carboxylic acids) is via subsequent reactions of 4,6-dichloro-2-methylthiopyrimidine-5-carbonitrile with amines and methyl glycinate. In some examples, the reaction of methyl N-(4-chloro-2-methylthio-6-pyrimidinyl)aminoacetate with amines occurs to give the corresponding acid amides. The previously unknown synthesized derivatives of pyrimidin-6-yl amino acids and 4,5-diaminopyrrolo[2,3-d]pyrimidine- 6-carboxylic acids possess fungicidal properties.Vilnius University, Vilnius 2006, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 7, pp. 955–961, July, 2000.     

Synthesis and corrosion-protective properties of acetylenic esters of bicyclo[2.2.1]hept-5-ene-2-carboxylic acid

A procedure was developed for preparing acetylenic esters of bicyclo[2.2.1]hept-5-ene-2-carboxylic acid. The structures of the compounds were confirmed by IR and ¹H NMR spectroscopy. The Kovats indices of the compounds were determined, and their boiling points were estimated by gas-liquid chromatography. The protective properties of the esters against acid corrosion of steel were studied.Translated from Zhurnal Prikladnoi Khimii, Vol. 77, No. 8, 2004, pp. 1331–1335.Original Russian Text Copyright © 2004 by Mamedov.     

Asymmetric synthesis of 6-formyl-1-alkoxycarbonylbicyclo[3.1.0]hex-2-ene-2-carboxylic acids by a novel buffer-mediated rearrangement

Asymmetric synthesis of 6-formyl-1-alkoxycarbonylbicyclo[3.1.0]hex-2-ene-2-carboxylic acids has been achieved and the absolute configurations of the products of a novel buffer-mediated rearrangement have been established.     

Novel transformations of two kinds of chlorinated photo [2 + 2] cycloadducts of 2-pyrone-5-carboxylate

Novel reactions of 7,7-dichloro- and 7,7,8-trichloro-3-oxo-2-oxabicyclo[4.2.0]oct-4-ene-6-carboxylates 5 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in alcohol gave pyrano[4,3-b]pyran-2,5-diones 8 via (Z)-(2H-pyran-2-on-3-yl)butenoates 7. On the other hand, the same treatment of 7,7,8-trichloro-2-oxo-3-oxabicyclo-[4.2.0]oct-4-ene-5-carboxylate 6b afforded 2-oxo-3-oxabicyclo[4.2.0]oct-4,7-diene-5-carboxylate 14 via cyclobutene formation and S_N2′ displacement by attack of the alkoxy anion.