Some reactions of 1,3-Dichloro-2-azoniaallene Salts with heteronucleophiles

1,3-Dichloro-2-azoniaallene hexachloroantimonates ( 1 ) reacted with H₂S to give 1,2,4-dithiazolium salts 2 . With hydrazines 1,2,4-triazolium salts ( 3, 4 ) were formed. 1,3-Dimethylurea, respectively 1,3-dimethylthiourea or ethyl allophanate, reacted with 1 to afford 2-oxo- or 2-thioxo-1,3,5-triazinium salts ( 5–7 ). With diphenylmethaneimines imino substituted 2-azoniaallene salts 8 were produced. From chloroacetonitrile dichloropyrimidines 9 , and from the tricyanomethyl anion a hexatriene 10 and a triazine 11 could be prepared. The 1,5-dichloro substituted 2-azoniaallene salts 12 reacted as bifunctional electrophiles with nucleophiles such as benzophenone hydrazone or anilines, to furnish 1,3,5-triazinium salts 14 . Against benzohydrazide the allene 12j behaved as trivalent electrophile giving the bicyclic 1,3,5-oxadiazinium salt 13j , the constitution of which has been secured by a crystal structural analysis. The vinyl-2-azoniaallene salt 1i cyclized on heating to the 1,3-thiazinium salts 16, 17 . From 17 the triazinium salts 18 were prepared with alcohols.     

1,3-Diaza-2-azoniaallene Salts as Novel N3-Building Blocks: Preparation and cycloadditions to alkenes,alkynes, carbodiimides,and cyanamides

1,3-Diaza-2-azoniaallene salts R¹-NN⁺N R² 6 represent a new functional group. 1,3-Disubstituted triazenes 8 are oxidized with tert-butyl hypochlorite to stable open-chain N-chlorotriazenes R¹ NN NCl R² 9 , which at low temperatures with Lewis acids afford the reactive intermediates 6 . The salt 6a is stable below −50 °C and was characterized by spectroscopic and analytical data. Heterocumulenes 6 behave as positively charged 1,3-dipoles undergoing cycloadditions to many different multiple bonds to furnish 1,2,3-triazolium and tetrazolium salts, e.g. to both electron-rich and electron-deficient alkenes, alkynes, to one or both double bonds of 1,3-butadienes, to carbodiimides, and cyanamides (1,3-dipolar cycloaddition with inverse electron demand). With an allene, a butatriene and a pentatetraene the 4,5-dihydro-1H-1,2,3-triazolium salts 17–19 were obtained. The constitutions of four of the products were secured by X-ray structural analyses. 4,5-Dihydro-1H-1,2,3-triazolium salts 11 and 1H-1,2,3-triazolium salts 20 are aza analogues of Arduengo's and Wanzlick's nucleophilic carbenes.     

Ene Reactions and [2+2]Cycloadditions of Nitrilium Salts with Alkenes

N-Alkylnitrilium salts ( 1 ) undergo ene reactions with electron-rich di- and higher substituted alkenes 2 to afford either 2-azoniaallene salts ( 3, 6, 9, 11 ) (the nitrilium salt reacting as ene and the alkene reacting as enophile) or 1-azonia-1,4-pentadiene salts ( 10, 12 ) (the alkene reacting as ene and the nitrilium salt reacting as enophile). Competing with ene reactions tri- and tetrasubstituted alkenes and N-alkylnitrilium salts undergo [2+2]cycloaddition to furnish azetinium salts ( 8, 13 ). In solution, alkyl substituted 2-azoniaallene salts tautomerize to 2-azonia-1,3-butadiene salts ( 4, 5, 7 ). The constitutions of the 2-azoniaallene salt 6c and the azetinium salt 8 were secured by X-ray crystallographic analyses.     

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 .     

Azocoupling of Quaternary 1,2,4-Triazolium Salts to form 5-p-N,N-dimethylaminophenylazo-1,2,4-triazolium salts

Quaternary 1,2,4-triazolium salts 1 couple easily with p-N,N-dimethylamino-benzenediazonium salts to form azodyes 3 (5-N,N-dimethylaminophenylazo-1,2,4-triazolium salts), preferably under solid-liquid phase transfer conditions using chloroform or methylene chloride and triethylamine or DABCO. Zwitterionic 1,2,4-triazolium salts anhydro mercapto hydroxide, anhydro hydroxy hydroxide, and anhydro anilido hydroxide („nitron”︁) couple as well. The azodyes — as also well known from industrially used types — absorb in the region of 500 nm and have high extinction coefficients. Substituents in 1-, 3- or 4-position of the triazolium ring exert no clear substituent effects. The quaternary 1,2,4-triazolium salts were synthesized according to standard procedures.     

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.     

Kinetics and Mechanism of Azocoupling between quaternary 1,2,4-triazolium salts and p-N,N-dimethylamino benzenediazonium tetrafluoroborate

The kinetics of azocoupling between 1-benzyl-4-phenyl-, 1,3,4-triphenyl-, 4-benzyl-1-methyl-, 1,4-dimethyl-, 1,4-diphenyl-3-methylmercapto- and 3-benzyl-mercapto-1,4-diphenyl-1,2,4-triazolium salts, and p-N,N-dimethylamino benzenediazonium tetrafluoroborate are studied spectroscopically in methanol/water 1:1 (v/v) at various pH values following up the growing-in of the respective azodyes. The competing reactions of the diazonium salt with the solvent and the buffer (NH₃/NH₄Cl), and of some bleaching of the azodye formed were studied separately and accounted for in the kinetic treatment. From the pH dependence of the coupling rate constants and by application of kinetic models it turned out that not the widely accepted one-step deprotonation mechanism of the quaternary triazolium salts applied but a two-step mechanism comprising of pseudobase formation and their subsequent deprotonation is valid. Using the pertinent kinetic model the pK values of pseudo-base formation (pK_R+) and their deprotonation (pK_A) were determined by non-linear regression.     

On the Reaction of α-Chlorobenzylic Cations with Isocyanates

Isocyanates react as N-nucleophiles with α-chlorobenzylic cations ( 2 ) to give 1-oxoisoindolium salts ( 5 ). From the reaction of benzotrichlorides with SbCl₅ and isocyanates the extremely reactive hexachloroantimonates 5 with R² = Cl are isolated. Hydrolysis of these cyclic N-acyl iminium salts affords phthalimides 6 . Reaction of 5 k with dimethylcyanamide gives the 2-azoniaallene salt 13 . p-Tolyl isocyanate is Friedel-Crafts alkylated by p-chlorobenzotrichloride ( 1i ) in the presence of SbCl₅ to furnish the 1,3-oxadiazinium salt 7 , which is hydrolyzed to give the benzophenone 9 . With ethanol the acetals 10 and 11 are formed from 7 .     

Preparation of soluble poly(amide imide) derivatives with metal salts and phosphorous compounds

Soluble poly(amide imide) derivatives were prepared through the direct polycondensation of 1,2,4‐benzenetricarboxylic acid and three diamines—bis[4‐(3‐aminophenoxy)phenyl]sulfone, bis(4‐aminophenyl)‐1,4‐diisopropylbenzene, and 4,4′‐oxydianilne—in the presence of metal salts and phosphorous compounds. Phosphonium salt, which was used as the initiating species and was prepared by the reaction of the metal salts and phosphorous compounds, reacted with 1,2,4‐benzenetricarboxylic acid to form acyloxy phosphonium salt, and then the salt was reacted with a diamine for the preparation of the prepolymers. The prepolymers were converted into the corresponding poly(amide imide)s in a homogeneous solution state at 180°C. The poly(amide imide)s showed good thermal and mechanical properties. Glass‐transition temperatures were observed from 240 to 270°C in differential scanning calorimetry traces. A melting endotherm was not observed for the polymers with differential scanning calorimetry. The initial decomposition occurred around 400°C according to thermogravimetric analysis, and major weight loss was observed from 610 to 680°C. The poly(amide imide)s had comparatively good solubility in aprotic polar solvents at concentrations high enough (～30%) for the fabrication of various forms. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 1399–1407, 2002     

Rhodium‐Catalyzed Regioselective Synthesis of Isoindolium Salts from 2‐Arylpyridines and Alkenes in Aqueous Medium under Oxygen

A highly regioselective synthesis of pyrido[2,1‐a]isoindolium salts from 2‐arylpyridines and two equivalents of electron‐deficient alkenes catalyzed by rhodium is demonstrated. The reaction was carried out in aqueous medium at 110 °C using inexpensive oxygen as oxidant. Reverse aza‐Michael addition of the isoindolium salt occurs when the salt was treated with base to give a β‐disubstituted alkene product. A reaction mechanism involving an ortho C–H olefination of 2‐arylpyridine by alkene, intramolecular aza‐Michael addition, deprotonation at the β‐carbon of the alkene fragment followed by another Michael addition to give the final product is proposed.

     

The base-mediated cyclization of selected benzyl alkynyl sulfones with aromatic aldehydes: novel synthetic access to aryl-substituted 5,6-dihydro-1,4-oxathiin S,S-dioxides

Based on an unexpected product isolated during the LDA-mediated intramolecular cyclization of a benzyl alkynyl sulfones, a conceptually new cyclization method for the formation of 5,6-dihydro-1,4-oxathiin S,S-dioxides is demonstrated. The reaction affords products with (het)aryl groups at the 5- and 6-positions in 7–54% yield.     

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.     

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 ).     

Iminiumsalze in quantitativen Gas/Festköper- und Festkörper/Festkörper-Reaktionen

Iminium Salts in Quantitative Gas/Solid and Solid/Solid Reactions Iminium salts that are highly susceptible to hydrolysis are quantitatively prepared and reacted in the solid state without solvents or liquid phases. Atomic force microscopy AFM helps in elucidating the mechanism of these still unusual gas-solid and solid-solid syntheses by recording surface topographies of reacting crystals of L-histidine (10) and triphenylverdazyl (15) . Various imines add gaseous HCl or HBr to form stable iminium halides (1, 3, 4, 5, 11) even if frozen liquids of very weak heterocyclic bases are treated at low temperatures. Another way for quantitative yields of iminium salt hydrates (6) starts with solid primary ammonium halides and gaseous acetone. o-Phenylenediamines (7) give quantitatively 1,5-benzodiazepines (9) by solid state cyclization of bis-iminium salt intermediates (8) . Crystalline nitroxyls (12) and triphenylverdazyl (15) undergo stoichiometric one-electron transfer with gaseous NO₂ or XeF₂ to give nitrosonium (14) and azonium salts (17) . The solid state chlorination of tetramethylthiuramdisulfide (18) or dimethylthiocarbamoylchloride (20) yields phosgene dimethyliminiumchloride (Viehe salt 21 ) in quantitative yield. Solid Viehe salt is quantitatively treated with gaseous Cl₂ to give the trichloride 19 and solid SbCl₅ or PCl₅ to produce the hexachloroantimoniates (22) , -phosphates (23) . Solid brenzcatechol (24) , mercaptobenzimidazole (27) , p-nitroaniline (30) , N-methylbenzothiazolone-2-hydrazone (34) and acetophenone (41) are treated with 21 to give the corresponding chloroiminium salts (25, 28, 31, 35, 43) . p-Toluenesulfonamide (37) and 22 give the chloroiminium salt 38 . These quantitative solid-solid reactions are most easily run in ball mills with cooling device. The “waste-free” techniques achieve exclusion of moisture in an elegant way. The preparative use of the versatile products with nucleophiles is indicated. The three-step solid-state mechanisms are discussed.     

Orthoamide. LI. Push-Pull-Butadiene und Heterocyclen aus CH2-aciden Verbindungen und Orthoamiden von Alkincarbonsäuren

Orthoamides. LI. Push-Pull-Butadienes and Heterocycles from Alkyne Carboxylic Acid Orthoamides and CH₂-acidic Compounds The acetylides 4b, 4f react with N,N,N′,N′,N″,N″-hexamethylguanidiniumchloride ( 5 ) to give the orthoamides 6b, 6f , resp. From CH₂-acidic compounds and the orthoamides 6a, c, e can be obtained the push-pull-substituted butadienes 8a–8aj . The 2,3,5-trimethyl-thiadiazolium salt 9 does not condense with 6e , as other CH₂-acidic compounds do, instead the vinylogous guanidinium salt 10a is produced. On heating, the ketenaminals 8d, aa cyclize to give the pyridone-carbonitriles 11a, b , resp. From 4-amino-coumarins 12 and the orthocarboxylic acid amideacetals 13a, b and the ketenaminal 16 resp., the amidines 14a–c and the heterocyclic compounds 15a–c resp., are formed. The enamines 17a–c, 19a, b react with the orthoamides 6a–f to give the pyridine derivatives 18a–1, 20a–h and 21a, b , resp. Analogously, from 6-aminouracil 22 and 6a, b, e, f are formed the pure 7-dimethylaminopyrido[2,3-d] pyrimidines 23a, b or mixtures of compounds 23c, d and the isomeric 4-dimethylamino-pyrido[2,3-d]pyrimidines 24a, b resp., which can be separated via their salts 25a,b/26a,b . The heterocyclic compounds 30a–d, 32a,b can be prepared from the pyrazole derivatives 28, 31 resp. and the orthoamides 6a–f .     

2-(1H-1,2,4-三唑-1-基)乙酰胺的制备

以甲苯作带水剂,三氮唑和氢氧化钾水溶液反应制备三氮唑钾盐;以氯乙酸甲酯和甲胺为原料制备2-氯乙酰甲胺。再以乙腈为溶剂,使三氮唑钾盐和2-氯乙酰甲胺反应制备目的产物2-(1H-1,2,4-三唑-1-基)乙酰胺。着重考察了三氮唑钾盐和2-氯乙酰甲胺反应的反应温度、反应时间及其摩尔比对目的产物收率的影响。从而确定了2-(1H-1,2,4-三唑-1-基)乙酰胺的合成工艺条件为:在乙腈中回流反应,反应时间4 h,n(三氮唑钾盐)∶n(2-氯乙酰甲胺)=1.3∶1;在此条件下,2-(1H-1,2,4-三唑-1-基)乙酰胺的收率达87.5%。并用1H NMR,MS,IR,元素分析对其结构进行了表征。     

Allylic polymers. Diallyl 2-substituted succinate prepolymers and their properties

Diallyl 2-substituted succinates, obtainable via the addition of alkenes or alkylaromatics to maleic anhydride, undergo intramolecular cyclization during polymerization to low molecular weight prepolymers. The amount of this cyclization and the properties of the cured prepolymers are profoundly affected by the structure of these 2-substituents. Thus, the degree of cyclization decreases with these substituents in the order: aralkyl and isobutyl > unhindered alkenyl > alkyl > hindered alkenyl. Properties of thermosetting molding compounds based on these prepolymers are inferior to those of poly-(diallyl phthalate) molding compounds.     

Beiträge zur Synthese von Orthocarbonsäureamiden

The formamidinium salts 11a, c as well as the nitrile 12 react with sodiumhydride/dimethylamine in the presence of trimethylborate to give the ortho formic acid amide 3a . The orthoamides 6a and 16 can be prepared from the iminium salts 15 and 14 , resp. by the same procedure. Treatment of the azavinylogous formamidinium salt 15 with sodiumhydride and piperidine or morpholine in the presence of trime‐thylborate affords the orthoamides 6c and 6d , resp. By transamination of the azavinylogous aminalester 5a are accessible the orthoamides 6b—d . The vinylogous orthocarbonic acid derivative 17 can be obtained from the salt 14 and sodium alcoholates. The action of sodiumhydride, dimethylamine and trimethylborate on the iminium salt 18 produces a mixture of the orthocarbonic acid derivatives 7a, 8a, 9a . When the guanidinium salt 20 is treated with the same reagents the ortho‐amides 3a and 10a are obtained. The reduction of the salt 20 with sodiumhydride in the presence of several activating reagents (e.g. tetrabutyl orthotitanate, aluminiumisopropylate, trimethylborate) affords the orthoamide 3a . The reduction of the iminium salts 18 and 24 does not proceed clean, giving mixtures of various orthoformic acid derivatives. The form‐amidine 25 can be prepared by reduction of the salt 15 with sodiumhydride/trimethylborate with good yields. By the action of the corresponding carbanions on the guanidinium salt 20 can be obtained the carboxylic acid orthoamides 26—33 . By the same procedure the orthoamides of alkyne carboxylic acids 36a—h, j—n are accessible.     

Oxadiazoline and Ketoimine Palladium(II) Complexes as Highly Efficient Catalysts for Suzuki–Miyaura Cross‐Coupling Reactions in Supercritical Carbon Dioxide

The [2+3] cycloaddition of nitriles (RCN) with 2,2‐dimethyl‐3,4‐dihydro‐2H‐pyrrole 1‐oxide, in the presence of palladium dichloride (PdCl₂) gives the corresponding 2,3‐dihydro[1.2.4]oxadiazole (Δ⁴‐1,2,4‐oxadiazoline) palladium(II) complexes 1 – 4 in good yields. However, the Pd(II)‐assisted reaction of pentafluorobenzonitrile with the same pyrroline N‐oxide gives a mixture of oxadiazoline 5 , ketoimine 6 and pyrrolylbenzamide‐ketoimine 7 Pd(II) complexes, which affords upon heating in refluxing acetone the unprecedented fused tricyclic ketoimine complex 8 as the exclusive product. Under heating, compounds 5 and 7 transform to 6 , the latter undergoing intramolecular cyclization by nucleophilic attack of the amino moiety to the ortho carbon of the pentafluorophenyl ring leading ultimately to 8 . The compounds were characterized by IR, ¹H and ¹³C NMR, ESI⁺‐MS, elemental analyses and, in the cases of 3 , 6 , 7 and 8 , also by X‐ray diffraction analyses. The catalytic properties of the Pd complexes were evaluated in Suzuki–Miyaura cross‐coupling reactions, using supercritical carbon dioxide (scCO₂) as a green solvent. Cross‐couplings of aryl halides with phenylboronic acid give the desired biaryl products in quantitative yields, in a short reaction time, for substrate‐to‐catalyst molar ratios as high as 4.0⋅10⁴.     

“一锅法”制备2-芳环取代咪唑化合物

以氰基取代的芳环化合物为起始原料,采用一锅法经加成、缩合、闭环3步反应合成了6个2-芳环取代咪唑化合物。同时考察了反应过程中甲醇钠用量、闭环反应温度和反应时间对目标产物收率的影响,得到的最佳反应条件:n(甲醇钠)∶n(氰基化合物)=(0.08～0.12)∶1,反应温度80～90℃,反应时间3～8 h。产物结构通过熔点、核磁、质谱、元素分析进行了确证。