Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. VII. Synthese eindeutig N-acylierter Thiazolidin-2-one und Oxazolidin-2-one

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. VII. Synthesis of Unequivocal N-Acylated Thiazolidine-2-ones and Oxazolidine-2-ones A new synthetic route to N-acylated thiazolidine-2-ones and oxazolidine-2-ones is reported: The reaction of carboxylic acid chlorides with 2-alkoxy-2-thiazolines ( 1, 2 ) or -2-oxazolines ( 3 ) yields unequivocal N-acylated thiazolidine-2-ones ( 4–6 ) or oxazolidine-2-ones ( 7 ). Bifunctional acid chlorides, e.g. oxalyl chloride or thiophosgene yield compounds 11 and 12 .     

Chlormethyl-substituierte Heterocyclen aus Chlortetrolsäuremethylester

Chloromethyl Substituted Heterocycles from Methyl Chlorotetrolate Reaction of amidines, isothioureas or thioureas with methyl chlorotetrolate 1 leads to pyrimidin-4-ones 2 and 1,3-thiazines ( 3 ), respectively. Compounds 2 and 3 are starting materials for the synthesis of 6-chloromethyl-uracils ( 4 ), 1,3-thiazine-2,4-dione 5 and 6-benzylthiomethyl-thiazinone ( 6 ). 2-Aminothiazoles react with the ester 1 to yield 5-chloromethyl-thiazolo[3,2-a]pyrimidin-7-ones ( 7 ). The 5-oxo isomers 8 are obtained by reaction of thiazoles with ethyl γ-chloroacetoacetate. By reaction of 2-mercaptoimidazoles and 1 or chlorotetrolic acid the condensed 1,3-thiazinones ( 10 ) result. In the latter case the intermediate 9 is isolated. It can be cyclised to 10 by heating with acetic anhydride and sulphuric acid.     

Intermediates of Prostanoid Synthesis. Stereospecific conversion of (+)-5β-hydroxycyclopenten-2-yl-1β-acetic acid γ-lactone into (+)-1β-methoxycarbonylmethyl-2β,3β-(p-nitrobenzylidene)-dioxycyclopentan-5-one

Starting from (+)-5β-hydroxycyclopenten-2-yl-1β-acetic acid γ-lactone ( 1 ), (+)-1β-methoxycarbonylmethyl-2β, 3β-(p-nitrobenzylidene)-dioxycyclopentan-5-one ( 7 ) was prepared within 4 steps. Subsequent cleavage of the latter gives (−)-3β-hydroxy-1-methoxy-carbonylmethylcyclopent-1-en-5-one ( 8a ). Hydroxylation of the lactone ( 1 ) was found to give (+)-2β,3β,5β-trihydroxycyclopentyl-1β-acetic acid γ-lactone ( 2a ) with cis-oriented hydroxy groups in respect to the lactone ring. No formation of the trans-isomer, as has been reported earlier [4], was observed.     

Prostaglandins and prostaglandin intermediates. XV. Synthesis of 4-Oxo Carboxylic Acids and γ-Lactones by oxidative cleavage of homoallyl and homopropargyl ketones or alcohols

A convenient method to convert homoallyl or homopropargyl ketones or alcohols into 4-oxo carboxylic acids or γ-lactones is the oxidative cleavage of the multiple bond with potassium permanganate in diluted sulfuric acid. This is exemplified by the preparation of intermediates for the synthesis of 8-methylprostaglandin C₂. The oxidation of the allylic compounds with permanganate is compared with the oxidative cleavage by ozone/hydrogen peroxide, ozone/chromic acid or sodium periodate/potassium permanganate.     

Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. IX. Regiochemie der elektrophilen Cyclofunktionalisierung β,γ-ungesättigter Carbamidsäureester mit Brom – Synthese von Oxazolidin-2-onen und Tetrahydro-2H-1,3-oxazin-2-onen

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. IX. Regiochemistry of Electrophilic Cyclofunctionalization of β,γ-Unsaturated Carbamic Acid Esters with Bromine – Synthesis of Oxazolidine-2-ones and Tetrahydro-2H-1,3-oxazine-2-ones N,N-Disubstituted β,γ-unsaturated urethanes ( 1 ) and bromine react in methylene chloride at room temperature. The crotyl urethanes ( 1a – 1c and 1e ) and bromine give mixtures of corresponding saturated urethanes (dibromine adducts) ( 2a – 2c and 2e ), the oxazolidine-2-ones ( 3a – 3c and 3e ), and the tetrahydro-2H-1,3-oxazine-2-ones ( 4a – 4c and 4e ). The reaction of γ,γ-dimethylallyl urethanes ( 1f – 1h ) with bromine gives similar results. A useful synthetic route to N-substituted tetrahydro-2H-1,3-oxazine-2-ones ( 4l – 4q ) is demonstrated by the reaction of cinnamyl urethanes ( 1l – 1q ) with bromine.     

r-5-(α-Halogenbenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-one als Ringtautomere von α-(Arylaminocarbonyloxy)-β-halogen-dihydrochalkonen

r-5-(α-Halogenobenzyl)-3, t-4-diaryl-c-4-hydroxy-oxazolidin-2-ones as Ring Tautomers of α-(N-Arylaminocarbonyloxy)-β-halogeno-dihydrochalcones The reaction of chalcone halogenohydrins ( 1–3 ) with arylisocyanates does not stop at the stage of the α-arylaminocarbonyloxy-β-halogeno-dihydrochalcones ( 7 ), but the cyclic urethanes 4–6 are formed. Compound 7h was synthesized independently. The structure and stereochemistry of 4–6 and 7h were determined by ¹³C n.m.r. spectroscopy.     

Cyclisierungsreaktionen β, γ-ungesättigter Kohlensäurederivate. II. Reaktionen β, γ-ungesättigter Carbamidsäurederivate mit elektrophilen Reagenzien - Synthese von N-substituierten Oxazolidin-2-onen

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. II. Reactions of β,γ-Unsaturated Carbamic Acid Esters with Electrophilic Reagents — Synthesis of N-Substituted Oxazolidine-2-ones N,N-Disubstituted β,γ-unsaturated urethans have been cyclized to N-substituted oxazolidine-2-ones by dry hydrogen chloride in methylene chloride. The N-substituted urethan 1a reacts with hydrogen chloride to form the urethan 2a and the 2-oxazoline 3 Reaction of 1 with bromine yields the corresponding N-substituted 5-bromomethyl oxazolidine-2-ones 6     

Action of grignard reagents on 6-(α-styryl)pyridazin-3(2H)-ones; synthesis of some 4-Substituted 6-(α-Styryl)-pyridazin-3(2H)-ones

6(α-Styryl)pyridazin-3(2H)-ones ( 1a – e ) reacted with phenylmagnesium bromide and/or methylmagnesium iodide to give the 1,4-addition products, 4-phenyl and/or 4-methyl-6-(α-styryl)pyridazin-3(2H)-ones ( 3a–e ). The structures assigned to the products are established by electronic and infrared spectroscopy and by synthesis of authentic samples in most cases.     

Base Induced Isomerization of γ, δ-Epoxyketones

Base treatment of open-chain γ, δ - epoxyketones yields usually two cyclopropane derivatives, a trans-1-acy1-2(α - hydroxyalkyl) cyclopropane (II) and a 2-hydroxy-3-oxabicyclo[3, 1, 0] hexane (III). The NMR spectra and some other physical properties of compounds II and III and of some of their transformation products are reported.     

Synthesis and characterization of poly(ε-caprolactone) and copolyesters by catalysis with molybdenum compounds: polymers with acid-functional asymmetric telechelic architecture

Eight different molybdenum compounds were tested in the catalysts of ring-opening polymerization (ROP) of ε-caprolactone (CL). All homopolymerizations were conducted in bulk at 150 °C using a CL/molybdenum compound molar ratio of 200. Ammonium decamolybdate (NH₄)₈[Mo₁₀O₃₄] comes to be the best catalyst for ROP, based on its selectivity, short reaction times (2 h) and high conversions (98%). Aliphatic copolyesters with acid-funtional asymetric telechelic architecture -hydroxyl-ω-(carboxylic acid) (HA) were synthesized from lactones -such as CL, δ-valerolactone (VL) and γ-butyrolactone (BL)- by ring-opening copolymerization. HA-copolyesters, namely HA-poly(ε-caprolactone-co-γ-butyrolactone) (HA-PCB), HA-poly(δ-valerolactone-co-γ-butyrolactone) (HA-PVB) and HA-poly(ε-caprolactone-co-δ-valerolactone) (HA-PCV), were obtained at 150 °C in 2 h using ammonium decamolybdate as catalyt and water as initiator. A control of the degree of polymerization (DP, measured by NMR) can be achieved in the range between 6 and 24 for HA-PCB and HA-PCV, based on the initial monomer/initiator ratio. DP shows a linear dependence with M/H₂O ratio (where M=CL+(BL or VL)) in this range. The nature of hydroxyl and carboxylic acid end groups of HA-copolyesters was determined by ¹H and ¹³C NMR. Finally, HA-poly(ε-caprolactone-block-δ-valerolactone) (HA-PCbV) was successfully prepared by sequential copolymerization of HA-poly(ε-caprolactone) with VL and characterized by ¹H and ¹³C NMR, GPC and MALDI-TOF.     

Cyclisierungsreaktionen β,γ-ungesättigter Kohlensäurederivate. V . Reaktionen β,γ-ungesättigter Carbamidsäureester mit Sulfenylchloriden - Synthese von 3,5,5-trisubstituierten Oxazolidin-2-onen

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. V. Reactions of β,γ-Unsaturated Carbamic Acid Esters with Sulfenyl Chlorides — Synthesis of 3,5,5-Trisubstituted Oxazolidine-2-ones N,N-Disubstituted β,γ-Unsaturated urethanes 1 have been cyclized to 3,5,5-trisubstituted oxazolidine-2-ones 3 by aromatic sulfenyl chlorides in methylene chloride. The same oxazolidine-2-ones 3 were obtained by reaction of 5-bromomethyloxazolidine-2-ones 8 with thiophenols.     

Cyclisierungsreaktionen β, γ-ungesättigter Kohlensäurederivate. IV [1]. Synthese von N-substituierten Thiazolidin-2-onen und 2-Alkoxy-2-thiazolinen aus β,γ-ungesättigten Thiocarbamidsäureestern

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. IV. Synthesis of N-Substituted Thiazolidine-2-ones and 2-Alkoxy-2-thiazolines from β,γ-Unsaturated Thiocarbamic Acid Esters The reaction between N-substituted β,γ-unsaturated thiourethans and dry hydrogen chloride or bromine occurs in methylene chloride at room temperature. The thiourethans 1 a–4 a react with hydrogen chloride to give mixtures of corresponding 2-alkoxy-2-thiazolines 6–9 and the thiazolidine-2-one 11 a . A useful synthetic route to N-substituted thiazolidine-2-ones 11 is demonstrated by the reaction of N,N-disubstituted β,γ-unsaturated thiourethans with hydrogen chloride and bromine. The i.r. and H-n.m.r.-data of the compounds are described.     

Synthesis of Optically Active 4-Hydroxypyrazolidin-3-ones as precursors for β-amino-α-hydroxycarboxylic acid derivatives

The cis or trans-glycidic esters 1 or 7 give ring transformations with hydrazines affording optically active 4-hydroxypyrazolidin-3-ones 3 and 4 or 6 or 9 and 10 , respectively, in different regioselectivities. 4-Hydroxypyrazolidin-3-ones 3 and 9 can serve as precursors for enantiomerically pure β-amino-α-hydroxycarboxylic acid amides 5 and 11 by hydrogenation in the presence of Raney-Ni.     

Synthese von ω-Acetyl-α-methylenpolyencarbonsäureestern

Synthesis of ω-Acetyl-α-methylenpolyene Carboxylic Esters The α-methylenpolyene carboxylic acids 1 and 2 are highly active against Gram-positive bacteria. If this activity arises from an interference with the cell membranes, then an abrupt change in biological properties is to be expected with growing chain length of simple model compounds. To make these tests possible, we describe here the synthesis of a series of homologue esters of type 40 . Their synthesis was achieved by Wittig reactions of polyene αω-dialdehydes 6 with acetyl-methylentriphenylphosphoran 5a and the protected carboxy-methylmethylen triphenylphosphonium salt 8 .     

Regio- and stereoselectivity of 1-(Pyridazin-3-yl)-3-oxidopyridinium Betaines towards 2π- and 4π-conjugated olefins

1-(6-Phenyl) and 1-(6-(4-tolyl)-3-oxidopyridinium betaines ( 1a , b ) react as 1,3-dipoles with conjugated olefines, namely 4-vinylpyridine, ethyl cinnamate and styrene as 2π-1,3-dipolarophiles to give 2,6-cycloadducts [6-substituted-8-azabicyclo[3,2,1]oct-3-en-2-ones ( 3a , b , 4a , b and 5b )] and with butadiene and furan as 4π-dipolarophiles to give 2,4-cycloadducts [7-substituted-7-azabicyclo[4,3,1]deca-3,8-diene-10-one] and 3-6-phenylpyridazin-3-yl)-3-aza-10-oxatricyclo-[5,2,1,1^2,6]undeca-4,8-diene-11-one ( 9a ). Structural and configurational assignments were based on H.n.m.r. spectral analysis.     

Synthesis of γ‐Fluoro‐α, β‐unsaturated Carboxylic Esters from Saturated α‐Fluoro Aldehydes

γ‐Fluoro‐α, β‐unsaturated carboxylic esters 7a, 7b and 7d and 4‐fluoro‐4‐phenylbut‐3‐enoic ester ( 8 ) are obtained by two alternative pathways from 2‐fluoro aldehydes 5a—d , either by Horner—Wadsworth—Emmons reaction or by Wittig reaction. The aldehydes 5a—d are prepared by Swern oxidation of the corresponding fluorohydrins 4a—d . These are available from α‐olefins by bromofluorination, bromineby‐acetate replacement and subsequent hydrolysis.     

Furylvinylhalogenide. X [1]. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäurederivaten mit Hydrazinen

Furylvinylhalides. X. Reactions of β-Fur-2-yl-β-chloro-α-cyanoacrylic Acid Derivatives with Hydrazines β-Fur-2-yl-β-chloro-α-cyanoacrylic acid derivatives 3 react with hydrazines yielding 3-fur-2-yl-5-aminopyrazoles 5 or 3-fur-2-yl-4-cyanpyrazolin-5-ones 6 . In some cases the β-hydrazino-α-cyanoacrylic acid derivatives 4 , could be isolated.     

Dehydration of 2-(2-Arylethyl)-2-hydroxy-4-oxopentanoic Acids and their hydrazones to form heterocycles

Dehydration of 2-(2-arylethyl)-2-hydroxy-4-oxopentanoic acids 1 with hydrochloric acid/acetic acid, affords 3-(2-arylethyl)-5-hydroxy-5-methyl-2(5H)-furanones 4 . Compounds of type 1 and 4 represent suitable precursors for the formation of pyridazin-3-ones 7 as they smoothly react with hydrazine. A new series of s-triazolo[4,3-b]pyridazin-3-ones 12 and tetrazolo[1,5-b]pyridazines 15 are obtained from the 3-chloropyridazines 11 upon treatment with semicarbazide and sodium azide, respectively. Reaction of 11 with phenyl- acetyl-hydrazine provides 3-benzyl-6-phenyl-8-(2-phenyl-ethyl)-s-triazolo[4,3-b]pyridazine 13 via dehydrative cyclization of the intermediate 14 which was clarified to exhibit tautomeric equilibria between enol–hydrazine form A and keto–hydrazine form B by means of ¹H and ¹³C NMR spectroscopy. Attempts to synthesize 3-alloxy-pyridazines 18 by reacting 11 with sodium alloxide afford N-allyl compounds 17 .     

Konfigurative Zuordnung über sterisch definierte Epoxidringe. XI. Glycidonitrile. IV.1. Synthese von 1α-Methyl-2α-aryl-cyclohexan-1ß-carbonsäuren aus 4α-Aryl-2-methyl-1α-oxaspiro. octan-2-nitrilen

Determination of Configurations by the Aid of Sterically Corresponding Epoxides. XI. Glycidic Nitriles. IV. Synthesis of 1α-Methyl-2α-aryl-cyclohexane-1ß-carboxylic Acids from 4α-Aryl-2-methyl-1α-oxaspiro[2, 5]octane-2-nitriles The opening of an epoxide ring of the C-2-isomeric glycidic nitriles 1a–b with anhydrous HCl in dry Et₂O yields the corresponding chlorocyanohydrines 2a–b . Treatment of these chlorocyanohydrines with diluted NaOH does not give the expected α-chloroketones 3a–b , but only the original glycidic nitriles. Dehydrocyanation of the chlorocyanohydrines 2a–b is carried out by column chromatography on silica or neutral Al₂O₃. Favorskii rearrangement of the resulting α-chloroketones 3a–b gives the angular methylated carboxylic acid methyl esters 4a–b , which are converted to the acids 5a–b by saponification with NaOH in quantitative yield. Better reaction conditions for the Favorskii rearrangement of 1-acetyl-1-chloro-cyclohexanes are described.     

Die Reaktion von α,β-Dihalogen-propionitrilen mit monosubstituierten Hydrazinen - einfache Synthese 1-substituierter 3- bzw. 5-Amino-pyrazole

The Reaction of α,β-Dihalogeno-propionitriles with Monosubstituted Hydrazines — A Simple Synthesis of 1-Substituted 3- or 5-Amino-pyrazoles In methanol hydrazines 3 , and α,β-dihalogeno-propionitriles 1, 2 even at 0°C irreversibly yield 3 · HX, and α-halogenoacrylonitriles 4, 5 (A₁). Fast addition of alkyl- and aralkyl- hydrazines 3 to 4, 5 (C) gives 1-substituted 1-(2′-halogeno-2′-cyan-ethyl)-hydrazines 6 , the addition of arylhydrazines 3 to 4, 5 (D) 1-aryl-2-(2′-halogeno-2′-cyan-ethyl)-hydrazines 8 . In methanol 6 spontaneously cyclise (E) to hydrogen halides 7 · HX of 1-alkyl- and 1-aralkyl-3-amino-pyrazoles, 8 with 2 moles of acids (F) to salts 10 · 2HY of 1-aryl-4-halogeno-5-imino-pyrazolidines, and the free 10 spontaneously (G) to hydrogen halides 9 · HX of 1-aryl-5-amino-pyrazoles. Mechanisms (A₁), (C), (D), (E), (F), and (G) are proved by t.l.c., ¹H-n.m.r., and isolation of intermediates, the structures of 7 resp. 9 , using the significant ¹H-n.m.r.-parameter Δ. Simple general syntheses are described for 3-amino-pyrazoles 7 (R = H, alkyl, aralkyl) or 5-amino-pyrazoles 9 (R = aryl) starting with α,β-dihalogeno-propionitriles 1, 2 , and for α-bromo-acrylonitrile 5 .