Organophosphorus chemistry. 13 [1]. The Behaviour of 3-Aryliminoxindoles toward Alkyl Phosphites

3-Aryliminoxindoles ( 6a–c ) react with trialkyl phosphites (TAP, 2a–c ) only in presence of a protonating agent (H₂O or CH₃COOH) to give the respective dialkyl 3-(arylamino-2-oxo-1H-indol-3-yl)-phosphonates ( 9a–i ). Compounds 9 are equally obtained by reacting 6a–c with the appropriate dialkyl phosphite (DAP, 4a–c ) in absence of solvent. The role displayed by the arylimine-moiety on the reaction courses is discussed. A mechanism that accounts for formation of 9 from the reaction of anils 6 with TAP, is presented. Structural assignment are based upon analytical, chemical and spectroscopic (i.r., ¹H-n.m.r., ³¹P-n.m.r. and m.s.) results.     

Cyclofunktionalisierung von 2-Allyl-phenolen mit Schwefelchloriden 2,3-Dihydrobenzofurfurylthioether aus 2-Allyl-phenolen und aromatischen Sulfenylchloriden

Cyclofunctionalization of 2-Allyl-phenols with Sulfur Chlorides. Synthesis of 2,3-Dihydrobenzofurfuryl Thioethers by the Reaction of 2-Allyl-phenols with Aromatic Sulfenyl Chlorides Reactions of different substituted 2-allyl-phenols ( 2a – h ) with either phenylsulfeny chloride ( 3 ) or 4-methyl phenylsulfenyl chloride ( 4 ) yield the products of a cyclofunctionali zation 2-phenylthiomethyl 2,3-dihydrobenzofuranes ( 6a – h ) or 2-(4′-methylphenyl) 2,3-dihydrobenzofurane ( 7a – g ), respectively. The identification of the products was carried out by mass spectroscopy and ¹H-n.m.r.-spectroscopy. Isomeric compounds, i.e. 3-phenylthio 2,3-dihydrobenzopyranes ( 10 ) were not obtained. The reaction is Markovnilov-directed. In the case of the treatment of 2-allyl-phenols with 2-nitro phenylsulfenyl chloride ( 5 ) we have obtained mixtures of 2-(2′-nitrophenyl) thiomethyl 2,3-dihydrobenzofuranes ( 8a – d ) and of simple Markovnikov adducts, so-called β-chlorothioethers. The mixtures were identified by ¹H-n.m.r.- and mass spectroscopic ( 9a – d ) methods.     

β-Fur-2-yl-α-halogenacrylonitrile. VII. Reaktionen von β-(5-Brom-fur-2-yl)-α-bromacrylonitril mit Mercaptan,Thioharnstoff und Thioharnstoffderivaten

β-Fur-2-yl-α-halogenacrylonitriles. VII. Reactions of β-(5-Bromo-fur-2-yl)-α-bromoacrylonitriles with Mercaptans, Thiourea and Thiourea Derivatives β-(5-Bromo-fur-2-yl)-α-bromoacrylonitrile 1 reacts with ethylmercaptan to yield β-(5-bromo-fur-2-yl) β-ethylthioacrylonitrile 3 . With thiourea β,β′-thio-bis[β-(5-bromo-fur-2-yl)]-acrylonitrile 2 is formed. The pyrimidines 4 and 5 have been prepared by the reaction of 1 with s-methylthiourea and 2-aminothiazole, respectively. The structure of the new compounds were determined by means of x-ray analysis, ¹H-n.m.r., ¹³C-n.m.r. and mass-spectroscopy.     

Reactions of 2-arylhydrazones of 1,2,3-triketones with 1,2-diaminoethane. I. Synthesis and spectral characterization of 6-arylazo-2,3-dihydro-1H-1,4-diazepines and 3,10-diarylazo-4,9-dimethyl-5,8-diaza-3,9-dodecadiene-2,11-diones

Reactions of 3-arylhydrazones of 2,3,4-pentanetrione ( 1a–1e ) and 2-arylhydrazones of 1,3-diphenyl-1,2,3-propanetrione ( 1f–1l ) with 1,2-diaminoethane have been studied. It was found, that 3-arylhydrazones of 2,3,4-pentanetrione react with 1,2-diaminoethane with formation of 6-arylazo-2,3-dihydro-1,4-diazepines ( 2a–2e ) or the diarylazo derivatives of 4,9-dimethyl-5,8-diaza-3,9-dodecadiene-2,11-dione ( 3a–3e ). Analogous reactions of 2-arylhydrazones of 1,3-diphenyl-1,2,3-propanetrione yielded exclusively the derivatives of dihydrodiazepine. The structure of obtained products has been elucidated on the basis of i.r., m.s. and ¹H-n.m.r. spectra.     

Radikalreaktionen von N-Heterocyclen. I. Synthese und Struktur eines N,N-verknüpften Bipyrazols

Radical Reactions of N-Heterocyclic Compounds. I. Synthesis and Structure of an N,N-Linked Bipyrazole 5(3)-Amino-3(5)-(phenylamino)-pyrazole-4-carboxylic acid ethyl ester ( 1 ), which is a very good antioxidant, reacts under mild reaction conditions with dibenzoyl peroxide or with tert.-butoxy radicals under formation of a bipyrazole 4 . Evidence of the structure of 4 is given by ¹H-n.m.r., ¹³C-n.m.r., i.r. and u.v. spectroscopic measurements, respectively and especially by ¹⁵N-n.m.r. measurements of ¹⁵N labelled compounds 1 and 4 . The bispyrazole 4 reacts with Pb(IV)-acetate, the product isolated was the 5-amino-e-anilino-1-(1-anilino-2-cyano-2-ethoxycarbonylethenyl-azo)-pyrazole-4-carboxylic acid ethyl ester (7). The formation of this substance is a chemical proof of the structure of 4 .     

Pyryliumverbindungen. 30. C-Alkylierung von 1,3,5-Triaryl-penten-1,5-dion-Enolaten: Ein einfacher Zugang zu 3-alkylsubstituierten 2,4,6-Triaryl-pyryliumsalzen

Pyrylium Compounds. 30. C-Alkylation of 1,3,5-Triaryl-pentene-1,5-dione Enolates: A Simple Approach to 3-Alkylsubstituted 2,4,6-Triarylpyrylium Salts 1,3,5-Triaryl-pentene-1,5-dione enolates ( 10 ), obtainable in crystalline form from 2,4,6-triarylpyrylium pseudobases ( 9 ) and sodium methoxide in benzene/ether, react in dipolar aprotonic solvents (e.g. DMSO, DMF) with various types of alkyl iodides to give C-alkylation products ( 11 ) which afford 3-substituted 2,4,6-triarylpyrylium salts ( 12 ) on treatment with perchloric acid. This reaction sequence proved to be a convenient synthetic route to pyrylium salts ( 12 ) having 3-oriented substituents such as normal or branched alkyl groups C_nH_2n+1 (e.g.n = 1–5), isotopically modified alkyl groups (e.g. C[²H₃], C₂[²H₅]), allyl type substituents (e.g. CH₂CHCH₂, MeCHCHCH₂, CH₂, CH₂CMeCH₂) or benzyl groups (e. g. PhCH₂, 4-Br C₆H₄CH₂). Bifunctional alkylating agents (e.g. 1,4-diiodobutane, o-xylylenediiodide) resulted in a novel type of bispyrylium salts ( 14 ) with 3,3′-linkage. The pyrylium salts obtained were characterized by their ¹H-n.m.r. and u.v. spectra as well as, in most cases, by transformation into the corresponding pyridine derivatives ( 13 ) and bispyridines ( 15 ) respectively.     

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 .     

Direct Synthesis of Pyrazoles via reaction of C-ethoxycarbonyl-N-arylnitrilimines with benzalmalononitriles and some α-cyanocinnamic acid derivatives

Reaction of C-ethoxycarbonyl-N-arylnitrilimines ( 2a–d ) with α, β-disubstituted acrylonitriles ( 3a–f ) in refluxing benzene affords the corresponding substituted pyrazoles 5a–f and 6a–c respectively in good yield. However, reaction of 2a–e with 3g gives the 2-pyrazoline derivatives 7a–d . The assigned structures for the products 5–7 were confirmed by their spectra (i.r., ¹H-n.m.r.) and elemental analyses. Also the structures of the pyrazoles 5 were substantiated by comparison with their regioisomeres 8 .     

Synthesis of biologically active 4-benzyl-1(2H)-phthalazinones and 2-aryl-3(2H)-1-benzal-isoindolinones

4-Benzyl-2-1(2H) phthalazonyl derivatives of type 2, 3, 5a, b were synthesized by Mannich reaction of 4-benzylphthalazinone 1 which by the reaction with diazomethane yielded O-methylated derivative 4 . Various 1-benzal-2-substituted aryl-3(2H) isoindolinones 7a–f, 8a–e were also prepared. Its i.r., ¹H-n.m.r. and mass spectra were discussed. Some of them exhibit pronounced antimicrobial activities. A number of phthalazinones have found application in clinical medicine [1–3] due to the their pronounced antipyretic, analgesic and tuberculostatic activity and the importance of some benzylidenephthalimidines as stabilisers for halogen containing high polymers [4] and the local anesthetic activity superior to that of procaine [5], tempted us to procure some new phthalazinones and isoindolinones with biological interest.     

Synthese und Strukturaufklärung von 19-Nor-pregnanderivaten mit stickstoffhaltigen Vierringen in 14,15-Stellung

Synthesis and Structural Elucidation of 19-Nor-pregnane Derivatives with Nitrogen-Containing Four-Membered Rings in 14,15-Position The introduction of a C₂ side chain in the 17-position of 3-methoxy-14β, 15β-(3′,4′-azetidine)-estra-1,3,5(10)-trien-17β-ol ( 1 ) is described. Hydroboration of the 17-ethylidene compound 4 gives a mixture of the 17αH and 17α-pregnane derivatives 6 and 6a in 70% and 10% yields, respectively. Birch reaction of 6 , followed by oxidation yields the 14β,15β-(3′,4′-azetidine)-19-nor-pregn-4-ene-3,20-dione ( 12 ). The new compounds were characterized by ¹H-n.m.r. The structure of product 13 was determined by X-ray crystallography.     

Synthesis,spectral data and extraction of copper by 1-(2′-Hydroxy-5′-alkylphenyl)-1-alkanone Oximes

1-(2′-Hydroxy-5′-alkylphenyl)-1-ethanone oximes with a normal alkyl group containing 2 to 12 carbon atoms and 1-(2′-hydroxy-5′-methylphenyl)-1-alkanone oximes containing 1 to 11 carbon atoms in the hydrocarbon chain were synthesized. Spectral data (u.v., i.r., n.m.r. and ¹³C) of oximes are reported. Four of these oximes were used for copper extraction from acidic solution. The results obtained indicate, that these oximes are better extractants than alkyl derivatives of 2-hydroxybenzophenone oximes.     

An Efficient Lanthanide‐Dependent DNAzyme Cleaving 2′–5′‐Linked RNA

RNA can form two types of linkage. In addition to the predominant 3′–5′ linkage, 2′–5′‐linked RNA is also important in biology, medicine, and prebiotic studies. Here, in vitro selection was used to isolate a DNAzyme that specifically cleaves 2′–5′ RNA by using Ce³⁺ as the metal cofactor, but leaves the 3′–5′ counterpart intact. This Ce5 DNAzyme requires trivalent light lanthanide ions and shows a rate of 0.16 min^?1 in the presence of 10 μm Ce³⁺; the activity decreases with heavier lanthanide ions. This is the fastest DNAzyme reported for this reaction, and it might enable applications in chemical biology. As a proof‐of‐concept, using this DNAzyme, the reactions between phosphorothioate‐modified RNA and strongly thiophilic metals (Hg²⁺ and Tl³⁺) were studied as a function of pH.     

Synthese neuer, 3-substituierter 2H-Thiopyran-Derivate via [4+2]-Cycloaddition mittels acceptorsubstituierter Enaminothione

Synthesis of New 3-Substituted 2H-Thiopyran Derivatives via [4+2] Cycloaddition Reactions using Acceptor Substituted Enaminothiones 3- and 4-Nitro acetophenones as well as 3- and 4-trifluoromethyl acetophenones react with POCl₃/DMF (Vilsmeier reagent) to give dimethyliminium perchlorates 1a–d after addition of perchloric acid to the reaction mixture. Substitution of the chloro atom in 1 by using sodium sulfide nonahydrate occurs under mild conditions (in case of nitro compounds at −5°C) leading to enaminothiones 2a–d . Reactions with acroleine and methylvinylketone in refluxing benzene give exclusively 2H-thiopyran derivatives 4a–h , which were isolated in good yields after spontaneous fast elimination of dimethylamine. In contrast, the introduction of 1-nitro-2-phenylethene as the dienophile allows stepwise reaction to give stable adducts 3k and 3l , respectively, and also 3m under mild conditions (reaction at room temperature). ¹H n.m.r. spectroscopic data as well as the elimination of dimethylamine to 4k–m permit the elucidation of the structure of adducts 3k–m .     

Ableitung und Diskussion rationeller 1H-NMR-Struktur-parameter für 1,3-bzw. 1,5-disubstituierte Pyrazolderivate

Discussion and Rationalization of ¹H-n.m.r. Parameters for the Structural Assignment of 1,3- or 1,5- Disubstituted Pyrazoles For 44 1,3-disubstituted ( 1 ) or 1,5-disubstituted pyrazoles ( 2 ) with growing polarity μ of solvent the ¹H-chemical shift δ (HC-5) (for 1 ) increases considerably more than δ (HC-3) (for 2 ), and, depending on the 5-substituent, δ (HC-3) often even decreases. This is interpreted in terms of nucleophilic interaction between polar solvent and “pyridine-like” pyrazole-(N-2), in enhancement of the contributions of polar canonical structures, in substituent effects, and in influences of the pyrazole dipole moments μ_r. Resultant dipole moments μ_r of disubstituted pyrazoles with the 3-resp. 5-substituents Me, Cl, NH₂, and OMe, and their projections μ′_r on the H-(C-5)-resp. H-(C-3)- bond axes are calculated. The chloro-pyrazoles 1h, 1i, 2h and 2i , 3-methoxy-, and 5-methoxy-1-benzyl-pyrazole are synthesized unambiguously. is recommended as significant parameter for the structural assignment of 1,3-disubstituted pyrazoles 1 and 1,5-disubstituted pyrazoles 2 .     

3,1′-Bridged 2-[2′-(4″-dialkylaminophenyl)ethenyl] pyrylium and 1-Benzopyrylium Dyes – Synthesis and Vis/NIR Absorption/Emission Behaviour

A series of new 3,1′-bridged 2-[2′-(4″-dialkylaminophenyl)ethenyl]-4,6-diarylpyrylium perchlorates ( 3 ), 2-[2′-(4″-dialkylaminophenyl)ethenyl]-7-diethylamino-1-benzopyrylium perchlorates 5–8 , 2-[4′-(4″-dialkylaminophenyl)butadien-1′,3″-yl]-, and 2-[2′-(7″-diethylaminocoumar-3″-yl)ethenyl]-7-diethylamino-1-benzopyrylium perchlorates 10–12 were synthesized and characterized by means of elemental analysis, m.p., Vis/NIR, and ¹H NMR spectra. Semiempirical MO calculations were performed to elucidate the essential features of the chromophores. The size of the bridging ring strongly affects the geometry of the chromophores which, in turn, determines the extent of charge transfer of the longest wavelength electronic transition. Increasing deviation from planarity causes the polymethine-like chromophore to become more polyene-like.     

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.     

Organoarsen-Verbindungen. XXVI. Zur Synthese der 1.3-Azarsoline

Organo-arsenic Compounds. XXVI. Synthesis of 1.3-Azarsolines 2-Aminoalkylarsines of the type RAs(H)CH₂CH₂NH₂ react with formic acid or carbonic acid chlorides to give the corresponding amides 1–3 , whereas reaction with iminoester hydrochlorides yields 1,3-azarsolines 4–6 . I. R.- and n.m.r.-data are reported.     

Kinetischer H/D-Isotopeneffekt der Photooxidation von 3,5-Dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazin durch Singulettsauerstoff

Kinetic H/D Isotope Effect of the Photooxidation of 3,5-Dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazine by Singlet Oxygen The hydrogen atoms of the thiazine ring and of the methyl groups of 3,5-dimethyl-1,1-dioxo-2-(p-tolyl)-1,2-thiazine 1a can be exchanged by deuterium in basic or acidic deutero methanol (CH₃OD). In CD₃OD/D₂SO₄ the rate of the H/D-exchange of the different protons of 1a was determined by ¹H-n.m.r. spectroscopy. A kinetic isotope effect of 1.5–1.8 was determined from the rate of the oxygen consumption and also by using a competitive method. The results are in accordance with an “ene” reaction of 1a with singlet oxygen.     

A novel synthesis of 1,3 Thiazetidine-2-one and 1,3-Oxazine-2-one Derivatives

In the reactions of acetylthioacetanilides ( 1a–c ) and diacetylthioacetanilides ( 3a–f ) with phosgene 1,3-thiazetidine-2-one ( 2a–c ) and 1,3-oxazine-2-one ( 5a–f ) were obtained respectively. The structures of new compounds were elucidated by elemental analyses, i.r., ¹H-n.m.r., m.s., for 1d–f by ¹⁹F-n.m.r. and for 2a and 5a by ¹³C-n.m.r. spectral data.     

Furanderivate. VII. 2-[Furyl-(2)- und 5-Nitro-furyl-(2)]vinylphosphonsäure-O,O-diethylester

Furanderivatives. VII. O,O-Diethyl-2-[furyl-(2)- and 5-nitro-furyl-(2)] vinylphosphonates Syntheses and spectroscopic properties (i.r., u.v., ¹H-, and ¹³C-n.m.r.) of the title compounds existing as E-isomers with the general structure 1–8 (R⁵  H, NO₂; R  CN, COOEt, H, NMe₂) are represented. According to spectroscopic data the compound 8 (R⁵  NO₂; R  NMe₂) differs in its electronic structure.