Reactions with 2-thiazolin-5-ones. III. The behaviour of 4-Arylazo-2-alkoxy-2-thiazolin-5-ones toward amines and Grignard reagents

Treatment of 4-arylazo-2-alkoxy-2-thiazolin-5-ones 4a – f with glycine or phenylhydrazine effects their conversion into 1-aryl-5-alkoxy-1 H-1,2,4-triazole-3-carboxylic acid derivatives 5a – j , with the loss of hydrogen sulfide. On the other hand, the reaction of the 2-ethoxy ( 4a – c ) and the 2-isopropyloxy ( 4g – i ) derivatives with strong basic amines involves the loss of an alkyl mercaptan to yield the N-substituted amines 7d – j of 1-aryl-Δ²-1,2,4-triazolin-5-one-3-carboxylic acids. The 2-benzyloxy derivatives 4d – f react with the same reagents to give the N-substituted amides 2a – g of 1-aryl-Δ²-1,2,4-triazolin-5-thione-3-carboxylic acids, with the loss of benzyl alcohol. Hetero-ring opening of 4 , followed by recyclisation, occurs upon treatment with ethyl or phenyl magnesium halides to yield the triazolinethione derivatives 13 a – c .     

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.     

Dithiocarbonsäuren,Dithiocarbonsäureester oder Thiocarbonsäureamide aus methylenaktiven Chlormethylverbindungen und Schwefel

Dithiocarboxylic Acids, Dithiocarboxylic Esters, or Thiocarboxylic Amides by Reaction of Methylene-active Chloromethyl Compounds with Sulfur With a mixture of sulfur and amine in DMF at room temperature halomethyl compounds ( 1 , 5 – 10 ) can be oxidized to give thiocarboxylic acids ( 2 , 11 – 16 ) and their derivatives ( 3 , 4 , 17 – 35 ). We studied this reaction in detail especially with chloroacetic derivatives ( 11 – 15 ) or chloromethyl heterocycles ( 16 ) formally derived from chloroacetic acid. The resulting thiooxalic acid derivatives ( 11 – 27 ) represent activated acids and very useful C₂-synthons, especially for the synthesis of heterocycles. Oxidation in the presence of triethyl amine leads to dithiocarboxylates ( 11 – 16 ) which can be alkylated to dithioesters ( 17 – 27 ) in high yields. As a rule, with different primary and secondary amines instead of tertiary amines these dithiocarboxylates or dithiocarboxylic esters can be transformed already at low temperatures to thioamides ( 28 – 35 ).     

Reactivity of the exocyclic double bond in 4-arylidene-2-phenyl-2-imidazolin-5-ones toward organomagnesium compounds. I

4-Arylidene-2-phenyl-1-substituted-2-imidazolin-5-ones 1a – d react with organomagnesium compounds, in ether at room temperature, to yield, as the main isolable products, the 4-disubstituted-methyl derivatives 2a – h . On the other hand, 1a – d react with phenylmagnesium bromide in a boiling ether-benzene mixture to give, among the reaction products, 2a – d and the 4-diarylmethylene derivatives 3a – d . Spectral data of 2 and 3 are discussed. Treatment of the GRIGNARD products 2a – c with formaldehyde and piperidine or morpholine effects aminomethylation at C-4 with the formation of the MANNICH bases 6a – f .     

Syntheses of 4-aroyl and 4-Disubstituted Hydroxymethyl-pyridazin-3(2H)-ones and Their 3-Mercapto Derivatives: Synthesis of 1,3-Dithiano[4,5-c]pyridazine as a New Ring System

A number of 4-aroylpyridazin-3(2H)-ones ( 2a – c ), 4-disubstituted hydroxymethyl-pyridazin-3(2H)-ones ( 3a – c ) and their thio derivatives ( 3d – f ) have been prepared from different Grignard reagents and 5,6-diphenyl-4-cyano( 1a ), 4-carbethoxy ( 1b )pyridazin-3(2H)-ones and 3-mercapto derivatives ( 1c and d ). The structures of the compounds prepared were inferred from their elemental analysis, spectral data and from the identity of some of them with authentic samples.     

α-Substituierte Phosphonate. 37. α-Pyrrolomethanphosphonsäurederivate und N-Vinylpyrrole

α-Substituted Phosphonates. 37. Derivatives of α-Pyrrolomethanephosphonic Acid and N-Vinylpyrroles Diethyl α-aminomethanephosphonate 5a and its α-aryl derivatives 5b–d react with 2,5-diethoxytetrahydrofuran 1 to give diethyl α-pyrrolomethanephosphonate 9a and the α-aryl derivatives 9b–d , respectively. The pyrrolo derivatives 9 can be converted into the lithium salts 15 and 16 , respectively, which with carbonyl compounds undergo the HORNER reaction yielding E/Z-mixtures of N-vinylpyrroles 18 . In certain cases the intermediate of the HORNER reaction, the β-hydroxyphosphonate 17 , can be isolated. The pyrrolo-analogue of stilbene, 18a , is formed only as E-isomer. On treating the lithium salts 15 and 16 with 9 or with alkyl halides α-C-alkylated pyrrolo-phosphonates 22 and 23 , respectively, are obtained.     

1,3-Acylumlagerungen bei der Cyclisierung von Thioharnstoffen mit Imidoylchloriden der Oxalsäure – Ein Zugang zu interessanten Thiocarbonylsystemen

1,3-Acylrearrangements by Cyclisation of Thioureas with Imidochlorides of Oxalic Acid – An Approach to interesting Thiocarbonylic Systems By cycloacylation of various substituted thioureas with bis-imidochlorides of oxalic acid the new thiazolidines 3, 4 and isomeric imidazolidines 5, 6 are obtained. Especially when triethylamine is used as a base the main products are the deeply coloured 4-arylimino-5-thioxo-imidazolidines which can be regarded as s-cis-configurated 1,4-dihetero-1,3-dienes. Some thiazolidines can be rearranged by means of anhydrous organic acids to parabanic acid derivatives; whereas the 5-thioxo-imidazolidines result from an intramolecular 1,3-acyl rearrangement during the reaction.     

Strukturelle Abwandlungen an N-Acetylneuraminsäure. 22 [1]. Zur Umsetzung von Methyl-5-acetamido-7,8-anhydro-4-O-t-butyldimethylsilyl-3,5-didesoxy-D-glycero- und L-glycero-β-D-galakto-nonulopyranosidonsäure-methylester mit Bis-imidazolylthiocarbonat

Structural Variations on N-Acetylneuraminic Acid. 22 On the Reaction of Methyl[5-Acetamido-7,8-anhydro-4-O-t-butyldimethylsilyl-3, 5-dideoxy-D-glycero-and-L-glycero-β-galacto-2-nonulopyranosid]onate with Diimidazolylthiocarbonate The title compounds 1 and 3 are transformed with diimidazolylthiocarbonate into the cyclic 8(S),9(O)-dithiocarbonatosialic acid derivatives 2 and 4 as well as into a mixture of the cyclic 8(S),9(O)-monothiocarbonato derivatives 5a and 5b , which turned with acetanhydride pyridine to the corresponding 4-O-t-butyldimethylsilyl-7-O-acetyl- and 4,7-di-O-acetyl derivatives 5c and 5d .     

Ringspaltung von 4-(4-Nitrophenylazo)-substituierten Pyrazolidin-3,5-dion – Derivaten zu α-(4-Nitrophenylhydrazono)semicarbaziden und Folgeprodukten

Ring Cleavage of 4-(4-Nitrophenylazo)-substituted Pyrazolidine-3,5-diones to α-(4-Nitrophenylhydrazono)semicarbazides with Consecutive Reactions The reaction of 1 and 2 with ammonia, methylamine and dimethylamine in aprotic solvents, e. g. diethyl ether, yields the compounds 3 – 8 which can exist in two isomeric forms (form a/b ). On conditions which are usually chosen for spectroscopic investigations only form a could be detected. Nevertheless, under the influence of bases like KOH or ammonia in water or alcohol these compounds are mainly converted to semicarbazides ( 11–15 ) which means that this reaction must run via form b . Those semicarbazides which are unsubstituted at the N-4 of their semicarbazide-moiety show great tendency to cyclize, thus forming the triazolederivatives 16–18 . In contrast to these products, in the case of the N-4-monomethylated semicarbazide 14 the six-membered heterocyclus 19 was obtained. In comparison with 1 and 2 , stable intermediates such as 3–8 in the reaction with 21 could not be isolated.     

Orthoamide. L. Beiträge zur Chemie von Propiolaldehydaminalen – Synthesen und Umsetzungen zu Push–Pull-substituierten Buta-1,3-dienen,Cyclobutanen sowie vinylogen Amidiniumsalzen und 1,2,3-Triazolen

Orthoamides. L. Contribution to the Chemistry of Propiolaldehydaminales – Synthesis and Transformations to Push–Pull-substituted Buta-1,3-dienes, Cyclobutanes, Vinylogous Amidinium Salts and 1,2,3-Triazoles Tert-butylaminalester 5 reacts with terminal alkynes to give aminals of substituted propiolaldehydes 3c, d . The aminal 3a is accessible from N,N,N′,N′-tetramethylformamidinium chloride (7b) and sodium acetylide. The aminals 3b,c can also be prepared from bis(dimethylamino)acetonitrile 8 and terminal alkynes in the presence of sodium hydride. The nitrile 8 is also useful for the preparation of the bis-aminal of acetylenedialdehyde 6 . The aminal 3e can be transaminated by heating with secondary amines to give the aminals 3f–i . The aminals 3a–i react with strong CH₂-acidic compounds (pK_a between 9 and 14) to give the 1-dialkylamino-1,3-butadienes 10 . The isomeric 1-dialkylamino-butadienes 18 can be obtained from the condensation of the CH-acidic cinnamic acid derivatives 19 with dimethylformamidedimethylacetal. CH and NH-acidic compounds as cyanacetamide react with the aminals 3c,e exclusively with the acidic methylene group to produce the enamines 10h,t . The acylformamidine 21 can be obtained from 10t and tert-butylaminalester 5 . The pyridone 22 is accessible from the condensation product 10h by thermal cyclization. The pyrido[2,3-d]pyrimidine 26 is formed in the reaction of the 6-amino-uracile 23 with the aminal 3a . In an unexpected reaction the 1,2-bis(cyano-dialkylaminomethylene)-cyclobutanes 28a–d result from the action of trimethylsilylcyanide on the aminals 3e–h . The corresponding reaction with trimethylsilylisothiocyanate affords the vinylogous amidinium thiocyanates 34a, b . In the reaction of trimethylsilylazide and the aminals 3 are produced the 4-(dialkylaminomethylene)-4H-1,2,3-triazoles 38 .     

Organische Phosphorverbindungen. VIII. Zur Solvolyse von Desmethyltrichlorphon (2,2,2-Trichlor-1-hydroxy-äthanphosphonsäuremonomethylester)

Organic Phosphorus Compounds. VIII. The Solvolysis of Desmethyltrichlorphone (2,2,2-Trichloro-1-hydroxy-ethanephosphonic Acid Monomethyl Ester) Desmethyltrichlorphone 3 , an in vivo metabolite of the insecticide Trichlorphone 1 , decomposes in aqueous solution to give monomethyl phosphate and dichloroacetaldehyde by a fragmentation and not – as hitherto supposed – by a rearrangement to desmethyl-DDVP 4 and its subsequent cleavage. In the same way desmethyl compounds of other Trichlorphone derivatives undergo fragmentation. In addition to the latter, 3 undergoes an HCl-elimination to the hydrate 19 of the 2,2-dichloro-1-oxo-ethanephosphonic acid monomethyl ester.     

N-Arylsulfonyl-N′-(pyrimidin-4-yl)ureas-synthesis and reaction with dimethyl sulfoxide

The N-arylsulfonyl-N′-(pyrimidin-4-yl)ureas ( 3a – 1 ) were synthesized by reaction of arylsulfonyl isocyanates ( 1 ) with 4-amino-2,6-dialkylpyrimidines ( 2 ). Treatment of 3 with alkali or of 1 with an excess of 4-amino-2,6-dimethylpyrimidine ( 2a ) gave the salts 4a – e . Reaction of the ureas 3a – c with dimethyl sulfoxide at 90 to 120°C afforded N,N′-bis(2,6-dimethylpyrimidin-4-yl) ureas 8a – c . The reaction is assumed to involve a four-centre mechanism with 5 as intermediate.     

Vinyloge Acylverbindungen. XIX. Vinyloge Acylgruppenwanderung am 2-Aminophenol. Ein Beitrag zum Isomerisierungsmechanismus gemischter Diacylderivate des 2-Aminophenols

Vinylogous Acyl Compounds. XIX. Vinylogous Acyl Group Migration in 2-Aminophenol. A Contribution to the Isomerization Mechanism of Mixed Diacyl Derivatives of 2-Aminophenol Starting with 2-acylaminophenols 5 and 2-(2-acylvinylamino)-phenols 6 the N-acyl O-acylvinyl derivatives 7 of 2-aminophenol and their N-acylvinyl O-acyl isomers 8 were prepared and characterized. These vinylogous acyl compounds are able to isomerize in the same manner as simple O,N-diacylated 2-aminophenols 3 and 4 , which under suitable conditions easily rearrange to give a dynamic equilibrium 3 ⇌ 4 . Contrary to 3 and 4 , however, the isomerization of 7 and 8 can be followed directly by spectroscopic methods, so that vinylogs of this type are useful model systems for studying acyl group migrations in 2-aminophenol. Kinetic measurements show that the mutual rearrangement of 7 and 8 is a reversible general based catalyzed reaction, being first order with respect to substrate and catalyst. The isomerization of the N-acetyl derivatives 7a – h as well as the N-benzoyl derivatives 7i – p results in strictly linear HAMMETT correlations with positive reaction constants ϱ. In the case of 7a – h the equilibrium constant K and the forward and reverse velocity constants k₁ and k₂ (including activation parameters) could be determined. The kinetic investigations and additional nonkinetic experiments indicate that the catalyst acts as proton acceptor and not — as hitherto supposed — as acyl group transferring nucleophile. Based on the findings an isomerization mechanism for mixed diacyl derivatives of 2-aminophenol is suggested.     

Bicyclische Oxalamidine – Bausteine für hochsubstituierte 2,2′-Bipyridine und Benzolderivate

Bicyclic Oxalic Amidines as Building Blocks for Highly Substituted 2,2′-Bipyridines and Benzene Derivatives The bis-imidoylchlorides 1 derived from oxalic acid exhibit a high regio- and chemoselectivity. As in the case of 2-picolylamine 2 the acylation with oxalyl chloride furnished the expected open chained oxalic diamides 3a while the imidoylchlorides 1 yield exclusively the new pyrido[1,2-a]-pyrazines 4 . These heterocycles represent readily crystallisable and orange-red coloured compounds with a mesomeric dipolar aromatic substructure. The synthetic value of 4 is based on their easy transformation into highly substituted arenes and hetarenes. Thus, electron deficient dienophiles as dimethyl acetylenedicarboxylate lead to the bipyridines 6 via Hetero-Diels-Alder-Reaction and subsequent 1,5-hydrogen shift. In a complex reaction the derivatives of maleic acid 7a – c yield the bipyridines of type 9 while the new hexasubstituted arenes 10 can be isolated under anaerobic conditions and with an excess of dienophilic component. A x-ray structural determination of 10b shows an alternation of bond lenghts in the benzene ring. This can be considered as a distinct disturbance of aromaticity caused by the arrangement of substituents.     

The knoevenagel reaction of cyanoacetamide with β-ketoanilides: Synthesis of polyfunctionally substituted pyridine and coumarine derivatives

Cyanoacetamide undergoes a Knoevenagel condensation reaction with β-ketoanilides 2a – c to give the acyclic products 3a – c . The reactivity of 3a towards the active methylene reagents, aldehydes, aryldiazonium salts and cinnamonitrile derivatives were studied.     

Zur Konstitution des Reaktionsproduktes aus Phenacylthioglykolsäure und Thioglykolsäure

On the Structure of the Reaction Product from Thioglycolic Acid and Phenacyl Thioglycolic Acid The reaction product obtained from phenacyl thioglycolic acid and thioglycolic acid is shown to represent 1,1,2-tris-(carboxymethylthio)-2-phenylethane 4 , and not 1,1,2-tris-(carboxymethylthio)-1-phenylethane 3 as suggested earlier in the literature. Analogously, phenacyl benzyl sulfide 2 and benzyl mercaptan yield 1, 1, 2-tris-(benzylthio)-2-phenylethane 5 . The reaction mechanisms are discussed on the basis of synthetic and n.m.r. spectroscopic studies.     

Studies on aminoazoles: Synthesis of Pyrazolo[1,5-a]-pyrimidines and their aza derivatives

The reaction of 4-arylazo-3-aminopyrazol-5-ones ( 1a – i ) with α,β-unsaturated nitriles, active methylene reagents and nitrile imines are reported. They lead to new polyfunctional derivatives of pyrazolo[1,5-a]pyrimidine ( 5a – c , 6 , 10a – i , 13a – c , 14a – c , 17a – d , 15 ), pyrazolo-[5,1-c]-1,2,4-triazine ( 22a – i ) and pyrazolo[5,1-c]-1,2,4-triazole ( 25a – c ). The structures of these products and the mechanisms of their formation are reported.     

Eine neue Synthese des Cinnamoyliminodithiokohlensäure-S,S-dimethylesters und Umsetzungen mit Nucleophilen

New Synthesis of Dimethyl-cinnamoylimino-dithiocarboxylate and Reactions with Nucleophiles A new general synthesis of dimethyl-cinnamoylimino-dithiocarboxylate 1d is possible by reaction of 4-nitro-cinnamoylamide with carbon disulfide in the presence of sodium hydride and following alkylation. With the unsubstituted dimethyl-cinnamoylimino-dithiocarboxylate 10 is in-vestigated the reaction behavior with nucleophilic compounds. The treatment of 1c with primary amines, respectively, by mono- and disubstitution of the methylthio groups yields isothiourea 2 or guanidines 3 . Benzocondensed heterocycles are formed by reaction of 1c with o-bifunctional nucleo-philes. The compounds 5, 6 and 7 have been synthesized from 1c with cysteamine, p-phenylenediamine and ethylenediamine. The oxadiazole 8 and isothiosemicarbazide 9 are obtained by reaction of the dithioester 1c with hydrazides. On the other hand cyclisation to the 1,2,4-triazole 11 over the intermediate 10 and to the 1,3,5-triazine 12 are possible. The reaction of 1c with carbanions in a basic medium affords acrylic derivatives 13 . In the same way we isolated by reaction of dithioester 1c with a benzothiazolium salt the dark coloured compound 14 . The physical properties of synthesized compounds are discussed by mass-, ¹H-n.m.r.-, i.r.- and u.v.-spectra.     

New Indenylidene‐Schiff Base‐Ruthenium Complexes for Cross‐Metathesis and Ring‐Closing Metathesis

We here report on the stability and catalytic activity of new indenylidene‐Schiff base‐ruthenium complexes 3a – f through representative cross‐metathesis (CM) and ring‐closing metathesis (RCM) reactions. Excellent activity of the new complexes was found for the two selected RCM reactions; prominent conversion was obtained compared to the commercial Hoveyda–Grubbs catalyst 2 . Moreover, excellent results were obtained for a standard CM reaction. Higher conversions were achieved with one of the indenylidene catalysts compared with Hoveyda–Grubbs catalyst. Unexpectedly, an isomerization reaction was observed during the CM reaction of allylbenzene. To the best of our knowledge, isomerization reactions in this model CM reaction in closed systems have never been described using first generation catalysts, including the Hoveyda–Grubbs catalyst. The first model CM reactions as well as the RCM reactions have been monitored using ¹H NMR. The course of the CM reaction of 3‐phenylprop‐1‐ene ( 8 ) and cis‐1,4‐diacetoxybut‐2‐ene ( 9 ) was monitored by GC. The isomerization reaction was studied by means of GC‐mass spectrometry and in situ IR spectroscopy. All catalysts were structurally characterized by means of ¹H, ¹³C, and ³¹P NMR spectroscopy.     

Self‐Assembled Multilayer‐Stabilized Nickel Nanoparticle Catalyst for Ligand‐Free Cross‐Coupling Reactions: in situ Metal Nanoparticle and Nanospace Simultaneous Organization

We have developed a conceptually and methodologically novel self‐assembled multilayer nickel nanoparticle (NP) catalyst – sulfur‐modified gold‐supported Ni NPs (SANi) – for organic synthesis. The SANi catalyst was easily prepared through a three‐step procedure involving simultaneous in situ metal NP and nanospace organization. This unique method does not require any conventional preformed template for immobilizing and stabilizing NPs. SANi catalyzes carbon‐carbon bond‐forming cross‐coupling, Kumada coupling, and Negishi coupling reactions under ligand‐free conditions and can be used repeatedly for these reactions. Physical analysis of SANi showed that the active species in these reactions are self‐assembled multilayer zerovalent Ni NPs with a size of ∼3 nm.