Supramolecular inclusion complexes of β-cyclodextrin with 4-(acyloxy)-4-(cyclopropylethynyl)-1-(2-ethoxyethyl)piperidines

4-Acyloxy-4-(cyclopropylethynyl)-1-(2-ethoxyethyl)piperidines have been synthesized by reaction of 1-(2-ethoxyethyl)piperidin-4-one with cyclopropylacetylene and subsequent acylation of intermediate 4-(cyclopropylethynyl)piperidin-4-ol. The resulting esters react with β-cyclodextrin to give supramolecular inclusion complexes. The complexation is accompanied by inclusion of the N-ethoxyethyl fragment of one substrate molecule in the inner cavity of one receptor molecule. The structure of 4-acyloxy-4-(cyclopropylethynyl-1-(2-ethoxyethyl)piperidines and their inclusion complexes with cyclodextrin has been studied by NMR spectroscopy.     

Investigation of supramolecular inclusion complexes with β-cyclodextrin of 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-hydroxypiperidine and 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-benzoyloxypiperidine oxalate by NMR spectroscopy

A comparative analysis of ¹H and ¹³C NMR spectra of 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-hydroxypiperidine, 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-benzoyloxypiperidine oxalate and their inclusion complexes with β-cyclodextrin was performed. The differences in values of chemical shifts of ¹H and ¹³C nuclei of the substrates and the receptor in the inclusion complexes were determined. It was found that the formation of complexes of 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-hydroxypiperidine and 1-(2-ethoxyethyl)-4-(pentyn-1-yl)-4-benzoyloxypiperidine oxalate with β-cyclodextrin was accompanied by insertion of one N-ethoxyethyl fragment of the substrate molecule into the inner sphere of one molecule of the receptor.     

Preparation and stereochemistry of methyl 3-(and 4)-p-chlorothiophenoxy-1-methylpiperidine-4-(and 3)-carboxylates,and cyclization to benzothiopyranopyridinones

The title piperidines were prepared by (a) methanolysis of the corresponding nitriles and (b) addition of p-chlorothiophenol to the appropriate tetrahydropyridines. Three esters were obtained with stereochemistry assigned by nmr analysis: 2 [3(a) SAr, 4(e) CO₂Me], 5 [4(e) SAr, 3(e) CO₂Me], 6 [4(a) SAr, 3(e) CO₂Me]. Compounds 2 and 6 cyclized in 70% sulfuric acid. The product structures were established by X-ray crystallography and, surprisingly, both had trans-fused rings. Compound 5 , however, did not cyclize but gave 4-(methylthio)chlorobenzene as the sole isolated product.     

Synthesis of Heterocycles from Arylation Products of Unsaturated Compounds: XIII. 5-R<Superscript>1</Superscript>-Benzyl-2-(R<Superscript>2</Superscript>-2-pyridylimino)thiazolidin-4-ones

Meerwein reactions of arenediazonium bromides with methyl and ethyl acrylates gave 3-aryl-2-bromopropionic acid esters which were subjected to cyclocondensation with N-(2-pyridyl)- and N-(6-methyl-2-pyridyl) thioureas to obtain 5-R¹-benzyl-2-(R²-2-pyridylimino)thiazolidin-4-ones. The latter were shown to exist in solution as E isomers of the imino form.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005, pp. 1071–1075.Original Russian Text Copyright © 2005 by Matiichuk, Obushak, Tsyalkovskii.     

NMR.-spektroskopische Methoden als Reinheitskriterien isomerer Weinsäuren und Weinsäureester

NMR.-spectroscopic Methods as Criteria of the Purity of Isomeric Tartaric Acids and Their Esters meso-Tartaric acid ( 2 ) can be distinguished either from the natural (+)-(2R, 3R)-tartaric acid ( 1 ) or the ‘unnatural’ (?)-(2S, 3S)-tartaric acid ( 1 ′) or their racemic mixture, by ¹H-NMR.-spectral resolution using europium chloride in aqueous solution. Diastereomeric esters have been prepared from different esters of tartaric acid 3 and the Mosher reagent 4 and the purities of the enantiomers of 3 have been checked by ¹H-NMR. spectroscopy.     

Synthesis of 1-(2-Ethoxyethyl)-4-hydroxy-4-[2-(1-hydroxycyclohexyl)ethynyl]piperidine and Heterocyclization under the Conditions of Hydration

The reaction of 1-(2-ethoxyethyl)piperidin-4-one with ethynylcyclohexanol led to the synthesis of a glycol, the hydration of which gave a mixture of spirocyclic compounds with a carbonyl group at various positions in the furan ring. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1649–1652, November, 2005.     

Synthesis of esters of 4-hydroxy-5-phosphinyl-2-imidazolidinone

The esters of 4-hydroxy-5-phosphinyl-2-imidazolidinone were prepared by reaction of urea with the esters of 2-hydroxy-2-phosphinylethanal in acidic medium. The ir, ¹H nmr and ³¹P nmr spectral data of the products are reported. All the isolated products had cis configuration. The stereochemistry of their formation is discussed.     

Synthesis and herbicidal activity of (Z)-ethoxyethyl 2-cyano-3-(2-methylthio-5-pyridylmethylamino)acrylates

2-Methylthio-5-pyridinemethylene amine was prepared from 2-chloro-5-methylpyridine. Ethoxyethyl 2-cyano-3,3-dimethylthioacrylate was prepared from ethoxyethyl cyanoacetate, carbon disulfide, and dimethyl sulfate in 86.2% yield. Its reaction with 2-methylthio-5-pyridinemethylene amine yielded (Z)-ethoxyethyl 2-cyano-3-methylthio-3-(2-methylthio-5-pyridylmethylamino)acrylate. Ethoxyethyl (Z+E)-2-cyano-3-ethoxyacrylate was synthesized from ethoxyethyl 2-cyanoacetate and triethyl or- thoacetate in 90.7% yield, and its reaction with 2- methylthio-5-pyridinemethylene amine yielded (Z)-ethoxyethyl 2-cyano-3-methyl-3-(2-methylthio-5-pyri-dylmethylamino)acrylate. The structures of all of the products were confirmed by ¹H NMR, elemental analysis, IR, and mass spectroscopy. The herbicidal activities of the products were evaluated, and the results of bioassay showed that (Z)-ethoxyethyl 2-cyano-3-methyl-3-(2-methylthio-5-pyridylmethylamino)acrylate exhibits good herbicidal activity on rape (Brassica napus) at a dose of 1.5 kg/ha. © 2003 Wiley Periodicals, Inc. 15:67–70, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10214     

4-Hydroxyquinol-2-ones. 87. Unusual Synthesis of 1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic Acid Pyridylamides

4-Chloro-2-oxo-1,2-dihydroquinoline-3-carboxylic acids and their esters react with aminopyridines in refluxing DMF to give the corresponding 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyridylamides. Their structures were proved by ¹H NMR and mass spectroscopy, counter synthesis, and by X-ray analysis. A possible mechanism is proposed for the indicated chemical reaction. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1362–1371, September, 2005.     

Synthesis of 4-amino-substituted but-2-en-4-olides

Previously unknown 4-amino derivatives of spiro-annelated Δ²-butenolide were synthesized by the addition of various amines at the activated triple bond of 4-hydroxy-2-alkynoic esters. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2761–2770, December, 2005.     

Synthesis and Characterization of Novel Methyl (3)5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates

Series of methyl 3- and 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates were developed and regioselectively synthesized as novel heterocyclic amino acids in their N-Boc protected ester form for achiral and chiral building blocks. In the first stage of the synthesis, piperidine-4-carboxylic and (R)- and (S)-piperidine-3-carboxylic acids were converted to the corresponding β-keto esters, which were then treated with N,N-dimethylformamide dimethyl acetal. The subsequent reaction of β-enamine diketones with various N-mono-substituted hydrazines afforded the target 5-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates as major products, and tautomeric NH-pyrazoles prepared from hydrazine hydrate were further N-alkylated with alkyl halides to give 3-(N-Boc-piperidinyl)-1H-pyrazole-4-carboxylates. The structures of the novel heterocyclic compounds were confirmed by ¹H-, ¹³C-, and ¹⁵N-NMR spectroscopy and HRMS investigation.     

Synthesis of 2-Functionalized 4-(Diethoxyphosphorylmethyl)-5-(1-bromoalkyl)furans and Their Reactions with Amines

Phosphorylation of esters and nitriles of 4-chloromethyl-5-alkylfuran-2-carboxylic acids with triethyl phosphite yields the corresponding phosphonates. These compounds are brominated with N-bromosuccinimide in carbon tetrachloride at the α-position of the alkyl radical. The resulting 2-(1-bromoethyl)-, 2-(1-bromopropyl)-, and 2-(1-bromoisobutyl)furans react with secondary amines following the scheme of nucleophilic substitution. The dehydrobromination product was isolated only in the reaction of ethyl 4-(diethoxyphosphorylmethyl)-5-(1-bromoisopropyl)furan-2-carboxylate with triethylamine, but its yield was low. The reactions of bromo phosphonates with lithium carbonate in DMF result in their decomposition.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 5, 2005, pp. 820–828.Original Russian Text Copyright © 2005 by Pevzner.     

Syntheses of 4-(benzo[b]furan-2 or 3-yl)- and 4-(benzo[b]-thiophen-3-yl)piperidines with 5-HT2 antagonist activity

The syntheses of 4-(benzo[b]furan-3-yl)piperidines, 4-(benzo[b]furan-2-yl)piperidines and 4-(benzo[b]thiophen-3-yl)piperidines with 5-HT₂ antagonist activity are described. Reaction of 1-acetyl-4-(2,4-difluorobenzo-yl)piperidine 2 with methyl glycolate gave methyl 6-fluoro-3-(1-acetylpiperidin-4-yl)benzo[b]furan-2-carboxylate 3 , which was converted to 2-[2-[4-(benzo[b]furan-3-yi)piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridin-3(2H)-one hydrochloride 9 . Analogous benzo[b]furans 17a-d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4-fluoro-2-(4-pyridinylmethoxy)acetophenones 20a,b afforded 4-(benzo[b]furan-2-yl)pyridines 21a,b , which were converted to 2-[2-[4-(benzo[b]furan-2-yl)-piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5-HT₂ antagonist activity in vitro.     

Two‐step synthesis of new 1,2,4,5‐tetrahydrospiro‐[3H‐2‐benzazepine‐3,4′‐piperidines] from 4‐iminopiperidines

New spiro[3H‐2‐benzazepine‐3,4′‐piperidines] and their precursors, N‐substituted 4‐allyl‐4‐N‐benzyl‐aminopiperidines, have been prepared as potential psychotic agents from readily available 4‐iminopiperidines, by a sequence of reactions that included nucleophilic addition of Grignard reagents and Bronsted acid‐mediated intramolecular cyclisation. Some of the compounds prepared have been tested in albine mice for spontaneous motor activity. All compounds prepared were characterized by ir and ¹H nmr spectroscopies and cg‐ms spectrometry.     

Tautomerism of azine derivatives. 4. Keto-enol tautomerism of β-keto esters of the azine series

The structures of pyrazinoyl-, 3-pyridazinoyl-, 4-pyrimidoyl-, and 2-, 3-, and 4-pyridoylacetic esters were studied by means of IR, NMR, and¹H and¹³C NMR spectroscopy and quantum-chemical calculations (Pariser-Parr-Pople and CNDO/2). The effect of solvents (including strongly and weakly basic solvents) on the position of the tautomeric equilibria of these β-keto esters was studied. The o⁺ constants for the keto and enol fragments were estimated by means of quantum-chemical calculations and¹³C NMR spectroscopy. See [1] for communication No. 3. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 822–826, June, 1980.     

Transition-Metal-Free Multiple Functionalization of Piperidines to 4-Substituted and 3,4-Disubstituted 2-Piperidinones

Remote and multiple functionalization of piperidines without the use of transition-metal catalysts and elaborate directing groups is one of the major challenges in organic synthesis. Herein is reported an unprecedented two-step protocol that enables the multiple functionalization of piperidines to either 4-substituted or trans-3,4-disubstituted 2-piperidones. First, by exploiting the duality of TEMPO reactivity, which under oxidative and thermal conditions fluctuates between cationic and persistent-radical form, a novel multiple C(sp³)-H oxidation of piperidines to α,β-unsaturated 2-piperidones was developed. Second, the intrinsic low reactivity of the unsaturated piperidones toward conjugated Grignard additions was overcome by using trimethylsilyl chloride (TMSCl) as Lewis acid. Subsequently, conjugated Grignard addition/electrophilic trapping protocol provided substituted 2-piperidone intermediates, some of which were then transformed into pharmaceutical alkaloids.     

Esters of Substituted 2,3,7-Triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acids and 1,2,7-Triazaspiro[4.4]non-2-ene-3-carboxylic acids in Alkylation and Acylation

Esters of substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acids react with acetone in the presence of hydrogen chloride (bromide) affording esters of substituted 2-(1,1-dimethyl-3-oxobutyl)-2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acids. Reactions of esters of substituted 2,3,7-triazabicyclo[3.3.0]octa-1(5),3-diene-4-carboxylic acids with 1-adamantanol in trifluoroacetic acid resulted in esters of substituted 2-(1-adamantyl)- 2,3,7-triazabicyclo[3.3.0]octa-1(5),3-diene-4-carboxylic acids.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005, pp. 252–263.Original Russian Text Copyright © 2005 by Stepakov, Molchanov, Kostikov.     

Preparation of Complexes η<Superscript>4</Superscript>-4-(1,3-Diphenyl-2-propen-1-one)-η<Superscript>3</Superscript>-3-(1,3,5-triorganyl-1,3,5-triazacyclohexane)carbonyltungsten(0) and Their Reactions with Diethyl Phosphite

New tungsten complexes were prepared of a composition η³-[(1,3,5-triorganyl)-1,3,5-triazacyclohexane]-tricarbonyltungsten(0) where a tridentate coordination of the triazinane fragment to the metal center was found. The reaction of tricarbonyltriazinane tungsten complexes with 1,3-diphenyl-2-propen-1-one (chalcone) under thermochemical activation resulted in replacement of two carbon monoxide molecules in the coordination sphere of tungsten by a chalcone molecule linked to the transition metal atom through a system of π-bonds C=C and C=O. The phosphorylation of η⁴-(1,3-diphenyl-2-propen-1-one)-η³-[(1,3,5-triphenyl)-1,3,5-triazacyclohexane]-monocarbonyltungsten(0) with diethyl phosphite occurred at the carbonyl group of the coordinated heterodiene; the phosphonate thus formed underwent intracomplex phosphonate-phosphate rearrangement affording an organometallic phosphate.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 5, 2005, pp. 793–797.Original Russian Text Copyright © 2005 by Kuramshin, Asafyeva, Cherkasov.     

Synthesis and structure of amides of 4-aryl(hetaryl)-2-pyrrolidone-3-carboxylic acids

Amides of 4-aryl(hetaryl)-2-pyrrolidone-3-carboxylic acids have been prepared via ammonolysis of the corresponding esters of pyrrolidone carboxylic acids. The products structure has been characterized by means of IR, ¹H NMR, ¹H–¹³C HMQC, and HMBC spectroscopy.     

Synthesis of alkyl- and phenyl-substituted 4-aminomethyl-2-buten-4-olides

4-Aminomethyl-2-buten-4-olides, 5-hydroxy-5,6-dihydro-2-pyridone, and isomeric 8,9-dihydro-4-cyano-2-oxofuro[2,3-c]piperidines were obtained by the base-catalyzed cyclization of 5-amino-4-hydroxy-4-alkyl-2-pentenoic acid esters. 5-Di-methylamino-3-methyl-4-oxovaleric acid ester and 4-dimethylamino-2-buten-4-olide, respectively, were isolated by isomerization of 5-dimethylamino-3-methyl-4-hydroxy-2-pentenoic acid ester and 4-dimethylamino-2-penten-5-olide in the presence of sodium isopropoxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1313–1319, October, 1987.