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. XI [1] Untersuchungen zur Stereochemie der Cyclofunktionalisierung β,γ-ungesättigter Carbamidsäureester

Cyclization Reactions of β,γ-Unsaturated Derivatives of Carbonic Acid. XI. Investigation of Stereochemistry of the Cyclofunctionalization of β,γ-Unsaturated Carbamic Acid Esters N, N-Disubstituted β,γ-unsaturated urethanes 1 have been cyclized to 3,5-disubstituted oxazolidine-2-ones 3 by aromatic sulfenyl chlorides 2 . The stereochemistry of the products and the cyclofunctionalization reaction were investigated.     

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     

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.     

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.     

An efficient Synthesis of Acetylenic γ- and δ-Hydroxy Ketones, γ- and δ-keto acids,and γ- diketones via addition of 1-alkinyllithium compounds to γ- and δ-lactones

2-Hydroxy-6-alkyn-5-ones 3 , 1-hydroxy-5-alkyn-4-ones 4 , and 1-hydroxy-6-alkyn-5-ones 5 are conveniently obtained in excellent yields through a highly selective monoaddition of an 1-alkynyllithium compound 2 to γ-valerolactone (1a) , γ-butyrolactone (1b) or δ-valerolactone (1c) . They are oxidized by pyridinium dichromate or Jones reagent to the corresponding acetylenic 1,4-diketones 6 , 4-oxo carboxylic acids 7 , and 5-oxo carboxylic acids 8 , respectively.     

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.     

Eine einfache Synthese von β-Chlorzimtsäurenitrilen nach einer modifizierten Vilsmeier-Haack-Arnold-Reaktion

A Simple Synthesis of β-Chlorocinnamonitriles by a Modified Vilsmeier-Haack-Arnold-Reaction A simple one-pot synthesis of β-chloro-cinnamonitriles 2 can be achieved by treating acetyl arenes 1 first with formamide chlorides and subsequently with hydroxyl amine hydrochloride. The formamide chlorides used are conveniently prepared from an excess of dimethyl formamide and phosphoryl chloride. However it is also possible to employ other N,N-disubstituted formamides or acid chlorides, respectively. For comparison purposes β-chloro-cinnamonitriles 2 have also been synthesized in a two-step process. Thus 3-aryl-3-chloro-(2)-iminium salts 4 are reacted with hydroxyl amine hydrochloride giving rise to 3-chloro-cinnamic aldoximes 5 . The latter compounds are dehydrated to the corresponding nitriles 2 by refluxing in acetic anhydride following a known procedure.     

New Intermediates and Dyes for Synthetic-polymer Fibres Derivatives of 2-Chloro-4-nitro-4‘-(N-β-hydroxyethyl-N- β-cyanoethylamino)azobenzene

Condensation of 2-chloro-4-nitro-4^t-(N-(β-hydroxyethyl-N-β-cy anoethylamino)azobenzene with various acid chlorides, chloroformates, isocyanates, isothiocyanates and reactive halogeno compounds gives dyes of excellent fastness to light and sublimation on polyester fibres.     

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.     

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.     

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.     

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.     

Synthese und Eigenschaften N-acylierter Thiophosphinsäureamide

Preparation and Properties of N-acylated Thiophosphinic Amides N-Acyl-, N-thioacyl- and N-sulfonyl-substituted thiophosphinic amides are prepared by the reaction of metallated acid amides with acid chlorides. The compounds exist as imides and form intermolecular hydrogen bonds. Their pK_a-values were potentiometrically determined and show a considerable acidifying influence of the thiophosphinic residues. Methylation of the imides with diazomethan gives predominantly S-methylesters of imidothiophosphinic acids.     

Reactions of α-Arylhydrazono-β-oxo-β-phenyl-propionitriles

ω-Cyanoacetophenone was coupled with a variety of aromatic diazonium chlorides to give the corresponding arylazo derivatives 1 a – g . Analysis of the IR and UV spectra of these compounds indicated that they exist mainly as the corresponding arylhydrazones. Compounds 1 a – d, f, g reacted with diazomethane to yield the N-methyl-arylhydrazones 2 a – f . 3-Amino-4-arylazo-5-phenylpyrazoles 5 a – g and 4-arylazo-5-imino-1,3-diphenyl-2-pyrazolines 6 a – g were obtained by the interaction of 1 a – g with hydrazine hydrate and with phenylhydrazine, respectively.     

Zur Chemie aktivierter Vinylhalogenide. Synthese und Reaktionsverhalten von 3-(β-Chlor-vinyl)-acrylnitrilen

Chemistry of Activated Vinyl Halogenides. Synthesis and Reaction Behaviour of 3-(β-Chlorovinyl)acrylonitriles Formamide chlorides 2 react with arylmethylketones 8 to give arylsubstituted β-chloro-vinyl-methinimmonium salts 4 which were converted by reaction with cyanoacetic acid derivatives 9 to 3-(β-chlorovinyl)acrylonitriles 7 . These nitriles react with various nucleophiles, such as aliphatic and aromatic amines, sodium sulfide, sodium thiosulfate, ammonium dithiocarbamates or alkali hydroxide to yield 3-(β-aminovinyl)acrylonitriles 10 or 19 , substituted 3-(β-hydroxyvinyl)acrylonitriles 14 , substituted 3-(β-mercaptovinyl)acrylonitriles 24 , 1,2-dihydro-2-imino-pyridines 12 , 2-amino-pyridinium salts 13 , 2-amino-pyrylium salts 15 , 2-pyridones 17 , 2-imino-2H-thiopyranes 26 , and 2-amino-thiopyrylium salts 18 , respectively. From the experimental results it was confirmed that the nitriles 7 have an ambident reactivity which can be interpreted theoretically on the basis of a simple HMO method. Some chemical reactions as well as u.v., i.r. and n.m.r. spectroscopical data confirm the structure of the reported compounds.     

Synthesis of new nitrile imines with Pyridazin-3(2H)-one moiety and their addition to some dipoles. I

The present work deals with the synthesis of 6-aryl-2-ethoxycarbonyl pyridazin-3(2H)-ones ( 2 ) as useful synthetic intermediates because they allow formation of a new hydrazides ( 3 ), hydrazidoyl chlorides ( 4 ) and the highly reactive nitrile imine species ( 5 ). Dimerization and reaction of the latter species with benzonitrile, benzaldehyde and their p-methoxy and p-nitro derivatives provides a convenient method for the synthesis of substituted 1, 2, 4, 5-tetrazines ( 6 ), 1, 2, 4-triazoles ( 7 ) and 1, 3, 4-oxadiazoles ( 8 ), respectively, with pyridazin-3(2H)-one moiety.     

Reactions with β-ketodianilides. I. New synthesis of Pyrido[3,4-c]pyridine Derivatives

Acetonedicarboxylic acid dianiline reacted with malononitrile, ethyl cyanoacetate or benzoylacetonitrile to give (6-amino-5-cyano-1,2-dihydro-2-oxo-1-phenylpyrid-4-yl)-acetanilide ( 3 ), (3-cyano-2,6-dioxo-1-phenyl-1,2,5,6-tetrahydropyrid-4-yl)acetanilide ( 8 ) or (3-cyano-1,6-dihydro-1,2-diphenyl-6-oxopyrid-4-yl)acetanilide ( 9 ). Compounds 3 and 8 could be cyclised into 8-amino-1,6-diphenyl-1,2,4,5,6,7-hexahydro-7-iminopyrido[3,4-c]pyridine-2,5-dione ( 4 ) and 7-amino-1,2,3,5,6,8-hexahydro-1,6-diphenylpyrido[3,4-c]pyridine-2,5,8-trione ( 10 ) respectively by heating their solutions in dimethylformamide in the presence of triethylamine. Each of 3 and 4 coupled with arenediazonium chlorides to give the corresponding arylhydrazone derivatives ( 5a–d ) and ( 6a–c ), respectively. Condensation of 4 with p-nitrosodimethylaniline yielded 8-amino-4- (p-dimethylaminophenylimino)-1,6-diphenyl-1,2,4,5,6,7-hexahydro-7-iminopyrido[3,4-c]pyridine2,5-dione ( 7 ).     

Vinyloge Acylverbindungen. XX. Reaktivität und Toxizität arylsubstituierter β-Chlorvinylketone, β-Chlorvinylaldehyde und β-Chlorvinylmethyleniminiumsalze

Vinylogous Acyl Compounds. XX. Reactivity and Toxicity of Aryl-substituted β-Chlorovinyl Ketones, β-Chlorovinyl Aldehydes, and β-Chlorovinyl Methyleniminium Salts Based on kinetic measurements, the nucleophilic replaceability of the chlorine in aromatic β-chlorovinyl ketones ArCO-CH  CH-Cl ( 1 ), isomeric β-chlorovinyl aldehydes OCH CHC(Cl)Ar( 2 ), and corresponding β-chlorovinyl methyleniminium salts Me₂N^⊕;CH CHC(Cl)Ar X^⊖ ( 3 ) is compared and related to toxicological findings. The chemical reactivity of these important synthetic building blocks increases in the order 2 < 1 < 3 , the acute toxicity (24 h LD₅₀ i. p. in the mouse) shows the graduation 2 < 3 < 1 . Compounds of type 1 prove to be relatively toxic (LD₅₀ 24–42 mg/kg) and display a marked necrotic action after percutaneous absorption, whereas the aldehydes 2 have not only a minor acute toxicity (LD₅₀ 158–298 mg/kg) but also a somewhat less marked skin damaging activity. In addition, the LD₅₀ values of selected β-chlorovinyl carbonyl compounds are compared with those of corresponding halogen-free compounds as well as of vinylogous carbonamidium salts ArCO CHCH N^⊕R₃X^⊖. The latter, which can be used as synthetic equivalents of 1 , differ in both the reduced acute toxicity and missing skin damaging properties.     

Rhodium‐Catalyzed Addition of α‐Keto Acid Chlorides with Terminal Alkynes

The addition reaction of α‐keto acid chlorides with terminal alkynes proceeds in the presence of (acetylacetonato)dicarbonylrhodium used as catalyst to afford synthetically versatile (Z)‐γ‐chloro‐α‐oxo‐β,γ‐unsaturated ketones regio‐ and stereoselectively.