Ringtransformationen heterocyclischer Verbindungen. I. 2-Amino-benzophenone und 7-Oxo-hepta-2,4-diennitrile durch Reaktion von 2,4,6-Triaryl-pyryliumsalzen mit 4-Nitro-benzylcyanid

Ring Transformations of Heterocyclic Compounds. I. 2-Amino-benzophenones and 7-Oxo-hepta-2,4-dienenitriles by Reaction of 2,4,6-Triarylpyrylium Salts with 4-Nitrobenzyl Cyanide 2,4,6-Triarylpyrylium salts 1 react with 4-nitrobenzyl cyanide in the presence of sodium acetate, triethylamine or triethylamine/acetic acid to give 7-oxo-hepta-2,4-dienenitriles 2 . With stronger bases such as sodium methanolate or ethanolate a ring transformation of the salts 1 occurs giving rise to 2-amino-benzophenones 3 which can also be obtained by cyclization of the nitriles 2 . Under the same conditions the 3-methyl-2,4,6-triphenylpyrylium salt 4 forms the 4-methyl-7-oxo-hepta-2,4-dienenitrile 5 by regioselective addition of the 4-nitrobenzyl cyanide at C-2 or it is converted to the 2-amino-5-methyl-benzophenone 6 . The ring transformation of the pyrylium salts 1 / 4 by 4-nitrobenzyl cyanide represents a new and simple method for the preparation of 2-amino-benzophenones. – Spectroscopic data of the novel compounds are discussed; the structure of 5 was confirmed by a single crystal X-ray analysis.     

Pyryliumverbindungen. 36. Substituierte Benzoesäureester aus 2,4,6-Triaryl-pyryliumsalzen und α-Ketocarbonsäureestern

Pyrylium Compounds. 36. Substituted Benzoic Acid Esters from 2,4,6-Triarylpyrylium Salts and α-Ketocarboxylic Acid Esters 2,4,6-Triarylpyrylium salts 1 react with α-ketocarboxylic acid esters 2 in the presence of two equivalents of an appropriate condensing agent (e.g. dialkylamine salts of weak acids, triethylamine/acetic acid, or sodium acetate) to give 2-aroyl-3,5-diarylbenzoic acid esters 3 . However, using only one equivalent of the condensing agent, the formation of 3,5-diarylbenzoic acid esters 5 predominates. Alkaline saponification of the new esters 3 and 5 yields the corresponding substituted benzoic acids 4 and 6 , respectively. – I.r., u.v., n.m.r. and mass spectroscopic data of the novel products 3 – 6 are reported.     

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 .     

Pyryliumverbindungen. 44 [1]. 2-(2-Hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyrane aus 2,4,6-Triaryl-thiopyryliumsalzen und Cycloalkan-1,2-dionen

Pyrylium Compounds. 44. 2-(2-Hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyranes from 2,4,6-Triarylthiopyrylium Salts and Cycloalkane-1,2-diones 2,4,6-Triarylthiopyrylium salts 5 react with cyclopentane-1,2-dione ( 2a ) or cyclo-hexane-1,2-dione ( 2b ) in the presence of an appropriate acid binding agent (e.g. sodium acetate, piperidine acetate, triethylamine/acetic acid, triethylamine) to give the hitherto unknown 2-(2-hydroxy-3-oxo-cycloalk-1-enyl)-2H-thiopyranes 6 . – The structure of the novel compounds was established by n.m.r., i.r. and u.v. spectroscopic methods.     

About nitrile-formamide-chloride-adducts. IX. Synthesis of 1,3- or 1,5-disubstituted 1,2,4-triazoles by the reaction of nitrile-formamide chloride-adducts and their products of hydrolysis with hydrazines

2-Aza-3-chloro-2-propeniminium salts 5 , which are easily available by the addition of formamide chlorides 1 to nitriles 2 react smoothly with hydrazines 9 giving rise to 1,3-disubstituted 1,2,4,-triazoles 11 . When the 2-aza-3-chloro-2-propeniminium salts 5 are hydrolysed first the resulting N-acyl-formamidinium salts 6 react with hydrazines 9 to 1,5 disubstituted 1,2,4-triazoles 13 via isolable N-acyl-formamidrazones 12 .     

On the Reaction of Acylium Salts with Isocyanates

Alkyl isocyanates ( 3 ) react with acylium salts ( 2 ) in a 2:1 ratio to furnish 3,4-dihydro-2,4-dioxo-2H-1,3,5-oxadiazinium salts 4. These cyclic N-acyliminium salts are decomposed with catalytic amounts of water to give either oxadiazinium salts 5 or pyrimidinium salts 7. With aqueous base compounds 4 are transformed into acylureas 6. Hetero substituted open chain N-acyliminium salts ( 8a , 11c , 12c , 13f , 15g , 16a ) are produced from 4 by treatment with heteronucleophiles such as methanol, p-anisidine, p-cresol, thiophenol, 1,3-dimethylurea, or benzohydrazide, respectively. Excess of nucleophile furnishes further degradation products of 4 , e.g. oxonium salts ( 9a ) and iminium salts ( 14f ).     

Reaktionen von β-Chlorvinylaldehyden. V [1]. Zur Bildung von 2,2′-Thiopyrylotrimethinfarbsalzen aus 2-(α-Formylalkyliden)-2H-thiopyranen

Reactions of β-Chlorovinylaldehydes. V. The Formation of 2,2′-Thiopyrylocyanine Dyes from 2-(α-Formylalkylidene)-2H-thipyranes Substituted β-chlorocrotonaldehydes react with Na₂S · 9H₂O to form 2-(α-formyl-alkylidene)-2H-thiopyranes 1 . The corresponding thiopyrylium salts 2 which are easily available from 1 and strong acids exist in the enolic form (2-β-hydroxyvinyl-thiopyrylium salts). They are converted at room temperature in methanol solution to dark green compounds, which are identified as 2,2′-thiopyrylotrimethincyanine dyes 3 . The mechanism of formation of compounds 3 is discussed.     

Synthese substituierter 2-Aminochinolin-1-oxide durch reduktive Cyclisierung substituierter 3-(2-Nitrophenyl)acrylnitrile

Synthesis of Substituted 2-Aminoquinoline-1-oxides by Reductive Cyclization of Substituted 3-(2-Nitrophenyl)acrylonitriles An approach to the class of 2-aminoquinoline-1-oxides is given based on reductive cyclization of appropriate substituted 3-(2-nitrophenyl)acrylonitriles. Thus, 2-nitrobenzylidene compounds 1 a – d have been reductively cyclized by H₂/PtO₂ or H₂/Pd-C under normal conditions to form N-oxides 2 a – d . ¹H-NMR data show that 1 d has to be regarded as ethyl(Z)-2-cyano-3-hydroxy-3(2-nitrophenyl)acrylate. The analogous (2-nitrobenzoyl)acetonitrile 3 , however, did not cyclize under the same conditions, but yielded anthraniloylacetonitrile 4 . The results are discussed in comparison with the reaction behaviour of structural related nitronitriles under comparable conditions. A short survey of reactions leading to heterocyclic N-oxides by reductive cyclization of nitro compounds is given.     

Synthesen und Eigenschaften Mono- und diphenylsubstituierter Monothio-β-dicarbonylverbindungen und ihrer Nickel(II)chelate

Syntheses and Properties of Mono- and Disubstituted Monothio-β-dicarbonyl Compounds and their Nickel(II) chelates Reaction of phenylacetaldehyde with phosphorous oxichloride and dimethylformamide yielded 3-chloro-2-phenyl-propenal, which was converted into 2-phenyl-monothiomalonic dialdehyde 2 by treating with sodium sulfide nonahydrate. Furthermore the reactions of other mono- and diphenylsubstituted monothio-β-dicarbonyl compounds with aniline on the one side and nickel(II)acetate on the other side have been studied. It was shown, that compounds 1–6 react in different way with aniline yielding either sulfur free products or in case of 1 and 4 enaminothioketones, which are of interest as building blocks for syntheses. In contrast to this the nickel complexes of 1–6 indicates an one another similar, typical chelate structure, which have been elucidated by u.v.-vis-, i.r.- and x-ray photoelectron spectroscopy.     

Tetrazolverbindungen. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazole aus 3-Chlor-propen-iminiumsalzen

Tetrazole Compounds. 1. 1-Aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles from 3-Chloropropeniminium Salts 3-Chloropropeniminium salts 1 react with excess sodium azide in refluxing alcohols to give mainly 1-aryl-5-(2-dialkylamino-vinyl)-1H-tetrazoles 3 ; in minor quantities isomeric 5-aryl-1-(2-dialkylamino-vinyl)-1H-tetrazoles 4 are formed. The reaction involves splitting off N₂ and C → N migration of the aryl and dialkylaminovinyl group, respectively. A cross-over experiment indicated that the rearrangement step proceeds intramolecularly. — The i.r., u.v., and n.m.r. spectroscopic data of the novel 1H-tetrazoles 3 as well as the u.v. spectra of some new starting products 1k—v are reported.     

Cycloadditions of 1-Aza-2-azoniaallene Salts derived from coumarin and camphor

The 1-aza-2-azoniaallene salt 8 prepared from 3-acetyl coumarin via the hydrazone 6 and the (chloroalkyl)azo derivative 7 reacts with nitriles to afford the 3-(3-chromenyl)-1,2,4-triazolium salts 11a–d . With diisopropylcarbodiimide the triazolium salt 13 and with norborene a tricyclic pyrazolium salt 14 are obtained. Concurrent to these cycloadditions the by-product 12 is formed by intramolecular cyclization of the cumulene 8 . Similarly, the intramolecular cyclization product 18 is isolated as the sole product when the 1-aza-2-azoniaallene salt 17a (prepared from the ethyl carbazone of camphor by chlorination and treatment of the product 16a with SbCl₅) was treated with nitriles, carbodiimides or alkenes. In contrast, 1,2,4-triazolium salts 20a–c , 23c , respectively pyrazolium salts 20d–f , and 1,3,4-thiadiazolium salts 23a,b are obtained by reaction of the 1-aza-2-azoniaallene salt 17b with nitriles, respectively alkenes, alkynes, diisopropylcarbodiimide, and isothiocyanates. The constitutions of two of these products ( 20e, 23a ) were secured by X-ray structural analysis.     

Reaktionen aromatischer Nitrile mit Dicarbonsäuredichloriden

Reactions of Aromatic Nitriles with Diacyl Dichlorides Dicarbonic acid dichlorides react with aromatic nitriles in the presence of SbCl₅ to give dicationic bis(1,3,5-oxadiazinium) salts 1. Reaction of 1 with ammonia or hydrazine yields derivatives of bis(1,3,5-triazine) ( 2 ) or bis(1,2,4-triazole) ( 3 ).     

3-取代苯基-5-羟基-5-三氟甲基异噁唑啉的合成

3 取代苯基 5 羟基 5 三氟甲基异口恶唑啉是合成具有异口恶唑结构的原卟啉原氧化酶抑制剂类除草剂的重要中间体。通过以下途径制得4个具有不同取代基的异口恶唑啉中间体:首先,在回流状态,n(甲醇钠)∶n(取代苯乙酮)=2∶1的甲醇钠存在下,取代苯乙酮与三氟乙酸乙酯缩合得到取代苯基 4,4,4 三氟 1,3 丁二酮;后者可在室温下,于二氯甲烷溶剂中,用氯化硫酰氯化,在侧链上引入氯原子;最后,以乙酸作溶剂,回流下,具有不同取代基的苯基 1,3 丁二酮与盐酸羟胺闭环得到产物。反应总收率大于95%。产品结构经质谱、核磁共振氢谱、碳谱确认正确。     

Pyryliumverbindungen. 42. Benzocycloalkenone und Dihydro-2H,7H-1-benzopyranone aus 2,4,6-Triaryl-pyryliumsalzen und Cycloalkan-1,2-dionen

Pyrylium Compounds. 42. Benzocycloalkenones and Dihydro-2H,7H-1-benzopyranones from 2,4,6-Triarylpyrylium Salts and Cycloalkane-1,2-diones 2,4,6-Triarylpyrylium salts 1 react with cycloalkane-1,2-diones 2 in the presence of an appropriate condensing agent to yield benzocycloalkenones 3 . Thus, sodium acetate and cyclo-hexane-1,2-dione ( 2a ) lead to the dihydro-2H-naphthalenones 3a – i , whereas with cycloheptane-1,2-dione ( 2b ) and piperidine acetate, triethylamine or sodium acetate the tetrahydro-5H-benzo-cyclohepten-5-ones 3j – r are formed. As shown for the example 3a, j → 4a, b , benzocycloalkenones of type 3 can be converted into phthalazines 4 on heating with hydrazine in ethanol. By reaction of the dione 2a and an equimolar mixture of triethylamine and acetic acid or morpholine acetate with the salts 1 5,6-dihydro-2H,7H-1-benzopyran-8-ones 5 are obtained as a result of a new type of ring transformation. The pyrans 5 can be cleaved with perchloric acid in ethanol to 5,6,7,8-tetrahydro-8-oxo-1-benzopyrylium perchlorates 6 . If the pyrans 5 are heated with sodium acetate in ethanol, a conversion to benzocycloalkenones 3 is achieved (cf. 5a → 3a ). The structure of the new compounds was established by spectroscopic methods.     

Synthesen von β-Fur-2-yl-α-halogenacrylonitrilen

Syntheses of β-Fur-2-yl-α-halogenacrylonitriles Syntheses of β-fur-2-yl-α-halogenacrylonitriles 2a–f by Wittig-olefination of furfurales, Hunsdiecker-reaction of β-(5-nitro-fur-2-yl)-α-cyanoacrylic acid 3 , halogenation of β-fur-2-yl acrylonitriles and reaction of furfurales with β-azido-α-halogen-γ-methoxy-Δ^α,β-crotonolactones 9 are described.     

Ringtransformationen heterocyclischer Verbindungen. XII. Neuartige Spiroindoline via Ringtransformation von 2,4,6-Triaryl-pyryliumsalzen mit 2-Methylen-indolinen

Ring Transformations of Heterocyclic Compounds. XII. Novel Spiroindolines via Ring Transformation of 2,4,6-Triarylpyrylium Salts with 2-Methyleneindolines 2,4,6-Triarylpyrylium salts 1 react with 2-methyleneindolines 2 or their salts 2 HX in the presence of triethylamine/acetic acid in ethanol by a 2,5-[C₄ + C₂] pyrylium ring transformation to give diastereomerically pure 6-aroyl-3,5-diaryl-spiro[cyclohexa-2,4-diene-1,2′-indolines] 3 , which represent a novel type of spiroindoline compounds. When the 1′-phenyl substituted spiroindolines 3 (RPh, R′H) are treated with p-toluenesulfonic acid in chloroform the 4,6-diaryl-2-[1-methyl-1-(2-phenylaminophenyl)methyl]benzophenones 4 are obtained as the result of an intramolecular amine elimination. Structural elucidation of the reaction products 3/4 is based on spectroscopic data and on an X-ray determination of the bis(4-bromophenyl) substituted spiroindoline 3i.     

Zur Synthese von 3-Amino-pyrrolen durch Thorpe-Ziegler-Cyclisierung

On the Synthesis of 3-Amino-pyrroles by Thorpe-Ziegler-Cyclization N-Aryl and alkylaminomethylene cyanacetic acid derivatives 1 react with α-halogencarbonyl compounds 2 in the presence of potassium carbonate/sodium ethoxide to yield the substituted 3-amino-pyrroles 6. Using the same principle of cyclization pyrrole derivatives 6 can also be obtained by reaction of β-chloro- and β-alkoxymethylenemalononitriles 4 with β-aminocarbonyl compounds 5. From the malononitrile derivatives 1 containing the methylthio group in the β-position, and α-halogen ketones 7 , the 2-dicyanomethylene oxazolines 8 arise which undergo alkoholysis by treatment with sodium alkoxide to form the 3-amino-5-alkoxy-pyrrole derivatives 9 .     

LINK Synthesis with 3-Hydroxy-1H-pyrazoles: 3-Carboxyisoalkyloxy-1H-pyrazoles – bicyclic acylpyrazolium salts and γ-Lactams – 3-Carboxyisoalkyloxy-4,5-dihydro-1H-pyrazol-5-ones

1-Substituted 3-hydroxy-1H-pyrazoles 1 react with chloroform, NaOH, and aceton resp. butan-2-one O-regiospecifically to yield 2-methyl-2-[(1H-pyrazol-3-yl)oxy]-propanoic resp. -butanoic acids 14 via a dichlorocarbene ( 12 )–dichlorooxirane ( 9 ) pathway. Chlorides 17 of 14 easily cyclize to N-acylpyrazolium salts 18/19 , which quantitatively afford esters 22–26 and amides 27–29 of 14 . Enantiomers of the butanoic acid 14th , obtained via their diastereomeric cholesterol esters, differ in their stimulus to peroxisome proliferation. At 140 °C pyrazolium salts 18 undergo thermolysis to bicyclic β-oxa-γ-lactams 30–32 . 3-Carboxyisoalkylamino-pyrazoles similarly give 1H-β-aza-γ-lactams 34 . Reactions of 14 with surplus SOCl₂ result in 6-chloro- 37 resp. 7-chloro-β-oxa-γ-lactams 38 via chlorosulfinylation and extrusion of SO, and in 4,4-bispyrazolyl-sulfoxide 39 . A mild introduction of additional O-functions into pyrazoles affording 4,5-dihydro-3-hydroxy-5-oxo-1H-pyrazoles 52–57 is presented. Biological effects of the new pyrazoles are protection against shock and ADP-induced thromboembolism, reduction of serum lipids and improvement of blood flow.     

Mehrfunktionelle N-Tenside. I. Nucleophile Substitutionen an Bischlornitrosoverbindungen 2. Reaktionen mit Thioharnstoff,substituierten Thioharnstoffen,Salzen und Estern von Dithiocarbaminsäuren und Mercaptoheterocyclen [1]

Polyfunctionalized N-Tensides. I. Nucleophilic Substitutions with Bischloronitroso Compounds. 2. Reactions with Thiourea, Substituted Thioureas, Salts and Esters of Dithiocarbamic Acid and Mercaptoheterocyclic Compounds Reaction of bischloronitroso compounds 1 with thiourea and substituted thioureas gives 2-aminothiazoles and 3-alkyl-2-iminothiazolines-(4). Ammoniumdithiocarbamate formes 4-thiazolinethiones-(2), and esters of the dithiocarbamic acids give 2-alkylmercaptothiazoles. N-substituted salts of dithiocarbamic acid and mercaptoheterocyclics react in boiling ethanol to form S-(β-oximinoalkyl)-dithiocarbamates 8 and in some cases 4-thiazolinthiones-(2) 9 .     

Pyryliumverbindungen. 45 [1]. 4-Aroyl-fluorene aus 2,4,6-Triaryl-pyryliumsalzen und Indan-1-on via 2-(5-Oxo-pent-2-en-1-yliden)-indan-1-one

Pyrylium Compounds. 45. 4-Aroyl-fluorenes from 2,4,6-Triaryl-pyrylium Salts and Indan-1-one via 2-(5-Oxo-pent-2-en-1-yliden)-indan-1-ones 2,4,6-Triarylpyrylium salts 1 react with indan-1-one in the presence of an appropriate buffer system (e.g. piperidine acetate, triethylamine/acetic acid, triethylamine or sodium acetate) to yield the 2-(1,3,5-triaryl-5-oxo-pent-2-en-1-yliden)-indan-1-ones 2 . For the reaction medium aliphatic alcohols (methanol, ethanol), dipolar aprotic solvents (acetonitrile) or chlorinated hydrocarbons (methylene chloride, chloroform, carbon tetrachloride) can be used. On treating 2 with sodium methanolate in methanol, a cyclization reaction occurs giving rise to the 4-aroyl-1,3-diaryl-fluorenes 3 . As by-products 1,3-diaryl-fluorenes 8 (e.g. 1,3-diphenyl-fluorene) are formed. - I.r., n.m.r. and u.v. spectroscopic data of the novel compounds 2 and 3 are reported.