Meerwein's Catalytic Beckmann Rearrangement

Meerwein recommended nitrilium salts ( 2 ) as catalysts for the Beckmann rearrangement of oximes ( 1 ) under neutral and water-free conditions. For the first time, primary adducts (Z)–( 3 ) of oximes to nitrilium salts have been isolated. Reported are activation energies for Beckmann rearrangements of these adducts, and an X-ray structural analysis of (Z)– 3a . Rearrangement of 3 produces mixtures of up to four different N-acylamidinium salts 5 – 8 , which arise from fast reactions of primary-formed secondary amides ( 4 ) with nitrilium salts ( 2 ). Because of their ambident electrophilic character the N-acylamidinium salts react with excess of oxime not only to amides ( 4 ) but to mixtures of products. It is shown that nitrilium salts cannot be used as catalysts for the Beckmann rearrangement.     

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.     

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 ).     

Energetic Salts of 5‐(5‐Azido‐1H‐1,2,4‐triazol‐3‐yl)tetrazole

Several metal and nitrogen‐rich salts of the recently presented 5‐(5‐azido‐1H‐1,2,4‐triazol‐3‐yl)tetrazole (AzTT), including silver ( 1 ), copper(I) ( 2 ), potassium ( 3 ), cesium ( 4 ), copper(II) ( 7 ), ammonium ( 8 ), and guanidinium ( 9 ), as well as the respective double‐salts of 3 , 4 , 8 and 9 , were prepared and well characterized by IR and multinuclear (¹H, ¹³C, ¹⁴N) NMR spectroscopy, DSC, mass spectrometry, elemental analysis and one ( 4 ) additionally by single‐crystal X‐ray diffraction. The sensitivities towards impact, friction and electrostatic discharge were determined according to BAM standards, revealing most of the metal salts as highly sensitive and the nitrogen‐rich salts as insensitive. The metal salts were further tested for their ability of being primary explosives.     

Synthese von Hetaryl‐pyridiniumsalzen und kondensierten 3‐Amino‐pyrid‐2‐onen

1‐(3‐Coumaryl)‐pyridinium salts 3 and 1‐(3‐coumaryl)‐tetrahydrothiophenium salts 5 were synthesized from 2‐acylphenyl chloro‐ or bromoacetates 2 . 2‐Chloro‐N¹‐(3,4‐dimethoxyphenyl)‐acetamide and substituted 2‐chloro‐N¹‐(2‐thienyl)‐acetamides 8 react with acetyl chloride and pyridine to yield the quinolinyl‐ and (thieno[2,3‐b]pyridin‐5‐yl)‐pyridinium salts 10 . Fused thieno[2,3‐b]pyridin‐ones 19 were formed from N‐chloroacetyl‐2‐aminothiophen‐3‐carbonitriles 16 with pyridine via Thorpe‐Ziegler cyclization and followed by cyclodehydrogenation. In presence of pyridine alkyl 2‐chloro‐acetylaminobenzoates 21 yield 3‐(1‐pyridinio)‐quinoline‐4‐olates 23 . Zincke‐cleavage of 10 and 23 with hydrazinium hydroxide leads to fused 3‐amino‐pyridine‐2‐ones 11 and 3‐amino‐4‐hydroxy‐quinoline‐2‐ones 24 , respectively. Oxazoloquinolines 25 were synthesized from 24 with acetic anhydride.     

Vinyloge Acylverbindungen. XVIII [1]. Einfluß sterischer Faktoren auf das Reaktionsverhalten vinyloger Carbonamidiumsalze

Vinylogous Acyl Compounds. XVIII. Influence of Steric Factors on the Reaction Behaviour of Vinylogous Carbonamidium Salts Depending on the size of their N-alkyl groups vinylogous carbonamidium salts show a markedly graduated reactivity under suitable conditions. Thus 2-formyl-vinyl trimethylammonium perchlorate 1a is decomposed by sodium hydroxide yielding only trimethylamine and salts of malondialdehyde 2 , while the analogous triethylammonium salt 1b additionally undergoes a fragmentation to triethylamine, acetylene and formic acid. The reaction of 4-(4-nitrobenzyl)-pyridine with 1 and the analogous 2-benzoylvinylammonium salts 3 to the 1,4-dihydropyridine dye 4 and 5 , respectively, is faster by orders of magnitude in the case R′ = CH₃ than in the case R′ = C₂H₅. Contrary to the 1a -p-nitrophenylhydrazone 6a which can be transformed into the pyrazole 7 the 1b -hydrazone 6b withstands such a ring closure. Depending on the reaction conditions and nature of the substituent R the action of aniline on 1 leads either to the monoanils 8 or to the malondialdehyde dianil salt 9 . While piperidine reacts with 3a as well as with 3b to give N-(2-benzoylvinyl)-piperidine 10 , aniline forms a corresponding vinylogous amide 11 only with 3a. 3b , however, on reaction with aniline · HCl via the intermediate monoanil 12 , yields the vinylogous amidinium salt 13 which is not obtainable from 3a or 11 . Using o-phenylendiamine this reactivity graduation can be utilized for preparing 2-aryl-substituted 1H-1,5-benzodiazepinium salts, e.g. 17 .     

Ring Transformations of Bicyclic Cycloalka[d]‐ to the Isomeric Cycloalka[c]isothiazolium Salts and their Oxidation to ω‐(2‐Aryl‐1,1,3‐trioxo‐2,3‐dihydro‐1H‐isothiazol‐4‐yl)‐alkanoic Acids

The synthesis of tetrahydro‐2,1‐benzisothiazolium salts 8 and cyclohepta[c] isothiazolium salts 11 by ring transformation of bicyclic isothiazolium perchlorates 2 , 3 is described and the by‐products 9 , 10 and 12 are characterized. Oxidation of the bicyclic salts 8 and 11 results in a new route to obtain ω‐(2‐aryl‐1,1,3‐trioxo‐2,3‐dihydro‐1H‐isothiazol‐4‐yl)‐alkanoic acids 17 and 18 by Criegee‐type‐rearrangement.     

New Aromatic Azapentalenes: 3H‐ and 2H‐Imidazo[1,2‐d]tetrazoles

A number of title compounds ( 3a,c,4a—c ) were prepared by cyclization of 5‐aminotetrazolium salts having ketonic substituents ( 1,2 ). The following procedures were applied: a) for 3a, 4a,b : heating of 1a, 2a,b with acetic anhydride‐ base; b) for 3c,4c : heating of 1b,2b in a buffer solution of pH 6.5 (Tschitschibabin reaction). The proclivity for ring closure was more pronounced with the salts 2 . The 6‐unsubstituted representatives 3c and 4c underwent S_E‐reactions, the 2H‐isomer 4c being slightly more reactive; this was confirmed by AM1 calculations. The nitroso product 4g exists predominantly as the valence‐isomeric nitrile oxide 6 .     

The use of N-bridgehead heterocyclic indolizinium ylide in the synthesis of aza-cyanine dyes

The reaction of 3-methyl-8-oxime-1-phenylpyrazolo [4,5-d]indolizinium (bezoindolizinium) ylide iodide with 2(4)-methyl substituted heterocyclic quaternary salts give 8[2(4)]-aza-monomethine cyanine dyes. Meanwhile, the reaction with carbonyl compounds followed by reaction with 2-methyl quinolinium methiodide salts afforded 5(2)-aza-trimethine cyanine dyes. On the other hand, the reaction of 5-formyl-2-methyl-4-phenylpyrazolo[4,5-d]indolizinium (benzoindolizinium) ylide iodide with hydroxylamine hydrochloride followed by reaction with N-methyl heterocyclic quaternary salts afforded the corresponding 5[4(1)]-aza-dimethine cyanine dyes. These new compounds are characterized with elemental analyses, visible absorption, IR, ¹³C NMR, ¹H NMR and mass spectroscopy. The correlations between the structure and spectral properties of these dyes have been studied.     

Atmospheric Pressure of CO2 as Protecting Reagent and Reactant: Efficient Synthesis of Oxazolidin‐2‐ones with Carbamate Salts,Aldehydes and Alkynes

Carbon dioxide (CO₂) has been wildly employed as an environmentally benign C₁ resource for organic synthesis in the recent years. The capture of CO₂ with primary amines easily provides the corresponding carbamate salts. We described herein that carbamate salts are a useful reactant for the synthesis of oxazolidin‐2‐ones via the reaction with aromatic aldehydes and aromatic terminal alkynes. A variety of oxazolidin‐2‐ones with different functional groups were synthesized in 68–91% yields with only a 5 mol% amount of CuI as catalyst. It was found that the synergetic effect of iodide is important for the transformation. Notable, the captured CO₂ serves not only as a protecting reagent for electron‐rich primary amine to avoid catalyst poisoning, but also as a reactant for the construction of oxazolidin‐2‐ones.

     

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.     

Formylation products of thioamides. XIII. Reaction of N-(3-aminothioacryloyl)-formamidines with amines – Synthesis of Pyrimidine Derivatives

N-(3-Aminothioacryloyl)-formamidines 3 react with primary amines to give either 4(1H)-pyrimidinthiones 6 or transaminated N-(3-aminothioacryloyl)-formamidines 5 . Alkylation of the latter compounds gives rise to cyclised 6(1H)-pyrimidinimines 7 . The 4(1H)-pyrimidinthiones 6 can be S-alkylated to 4-alkylmercaptopyrimidinium salts 8 . Subsequent substitution of the alkylmercapto group of the 8 results in the formation of 4-aminopyrimidinium salts 9 , which can also be obtained starting from the 3 by a reversed reaction sequence that is first by S-alkylation to 3-alkylmercapto-2-azapentamethinium salts 10 and subsequent reaction with primary amines.     

Regiocontrolled Synthesis of 4-Halo-5,6-Dihydro-4H-1,2-Oxazines; A Novel Route for α-Fluorovinyl Ketones

Regiocontrolled deprotonation (e.g. lithiation) of 3-methyl-4-H-5,6-dihydro-1,2-oxazine 1 is achieved at −65°C. The lithiated compound reacts cleanly with the halogens Cl₂, Br₂ and I₂ at low temperatures (−65°C) to give the corresponding 4-halo derivatives. Reaction of the 4-iodo compound 2a with KF in diethyleneglycol gives the elimination product 4 whereas the bromo compound 2b reacts under substitution to the 4-fluoro derivatives 5. The fluorooxazine derivatives 8a-c were converted to the αfluoroenones 11 a-c via the oxoiminium salts 10a-c. The U.V. and ¹HNMR of the novel series of halides 2a-c and 5 were studied.     

Tetrathiafulvalene. XXVIII. Diastereoselektive Bildung unsymmetrisch substituierter Tetrathiafulvalene

Tetrathiafulvalenes. XXVIII. Diastereoselective Formation of Unsymmetrically Substituted Tetrathiafulvalenes As a part of our work on chemistry of tetrathiafulvalenes, we make a contribution to elucidate the mechanism of forming tetrathiafulvalenes starting from 1,3-dithiole derivatives. We describe the synthesis of unsymmetrically substituted tetrathiafulvalenes ( 8a–i ) starting with the 2H-1,3-dithiolium salt ( 7a–i )/tert. amine, 2-ethylthio-1,3-dithiolium salt ( 5a–i )/triphenylphosphine or 1,3-dithiole-2-thione ( 4a–i )/triethyl phosphite. If the 1,3-dithiole derivatives are substituted by bulky groups the isolation of the cis- and trans-isomers was possible due to differences in the solubility. In these cases ( 8c–i ) the predominant formation of the cis-isomer is observed in the reaction of 2-ethylthio-1,3-dithiolium salts ( 5c–i ) with triphenylphosphine or 1,3-dithiole-2-thiones ( 4c–i ) with triethyl phosphite. This result is in agreement with the formation of an intermediate, analogously to the Wittig reaction. In the reaction of 2H-1,3-dithiolium salts ( 7a–i ) with tertiary amines the relation of isolated cis- and trans-isomers is not 1:1 and depends on the bulkiness of the tertiary amine. These observations exclude in these three reactions a carbene mechanism for the dimerization of the 1,3-dithiole units to tetrathiafulvalenes.     

Pyryliumverbindungen. XXVII. Spezifisch deuterierte Carbo- und Heterocyclen via 2,4,6-Triaryl-[3,5-2H2]pyryliumsalze

Pyrylium Compounds. XXVIII. Specifically Deuterated Carbo- and heterocycles via 2,4,6-Triaryl[3,5-²H₂]pyrylium Salts On heating with catalytic amounts of bases(e.g. triethyl amine) in deuterated alcohols such as methan[²H]ol or ethan[²H]ol pseudobases of 2, 4, 6-triarylpyrylium salts 1 undergo fast¹H/²H isotopic exchange reaction affording 1, 3, 5-triaryl[2, 4, 4-²H₃]pent-2-ene-1,5-diones which with [²H] perchloric acid give highly deuterated 2, 4, 6-triaryl-[3, 5-²H] pyrylium perchlorates 8 . These salts are obtainable also directly from 1 through a one-pot procedure by ring opening of the latter with deuterium oxide under the above-mentioned¹H/²H isotopic exchange conditions followed by recyclization of the formed 1, 3, 5-triaryl[2, 4, 4-²H₃]pent-2-ene-1, 5-diones with [²H]ClO₄. Ring transformations of 2, 4, 6-triphenyl[3, 5-²H²]pyrylium perchlorate (8a) to 2, 4, 6-triphenyl[3, 5-²H₂]nitrobenzene (9) 2, 4, 6-triphenyl[3, 5-²H₂]pyridine (10) , 1, 2, 4, 6-tetraphenyl[3, 5-²H₂]pyrydinium perchlorate (11) , 2, 4, 6-triphencyl[3, 5-²H₂]thiopyrylium perchlorate (12) , 2-benzoyl-3, 5-diphenyl[4-²H]furan (13) , and 3, 5, 7-triphenyl-[4, 4, 6-²H₃]4H-1, 2-diazepin (14) demonstrate the usability of pyrylium salts of type 8 as starting materials for syntheses of specifically deuterated carbo- and hetrocycles.     

Enantiodivergent Brucine Diol‐Catalyzed 1,3‐Dipolar Cycloaddition of Azomethine Ylides with α,β‐Unsaturated Ketones

Enantiodivergent catalyst systems were developed using metals with different ionic radii and a multifunctional brucine diol (BD) ligand. The catalytic use of purported 1:1 Cu‐BD complexes in the 1,3‐dipolar cycloaddition of azomethine ylides with chalcones resulted in the selective formation of endo‐pyrrolidines in 87–96% ees with an absolute stereochemical outcome of (2R,3S,4R,5S). In contrast, an opposite absolute stereochemical outcome was observed by using the catalysts derived from Ag(I) salts and BD. The demonstration of enantiodivergent approaches to a broad class of substrates/reaction types underlines their synthetic value in asymmetric synthesis.

     

Synthesis and antimicrobial activity of certain novel monomethine cyanine dyes

A series of novel monomethine cyanine dyes were synthesized by using 3-methyl-5-substituted-1-phenyl-pyrano[2,3-c]pyrazole derivatives 2a–c. Reaction of equimolar ratios of 2a–c with 2(4)-methyl heterocyclic quaternary salts afforded the corresponding monomethine cyanines 3a–c. Reaction of compound 5 with 2(4)-methyl heterocyclic quaternary salts gives monomethine 6a–c. Condensation reaction of equimolar ratios of compounds 7 and 9a,b with 2(4)-methyl heterocyclic quaternary salts afforded the corresponding monomethine cyanines 8a–c and 10a,b respectively. The new synthesized monomethine cyanine dyes were identified by elemental analyses, IR, ¹H-NMR and Ms spectral data. The electronic absorption spectra in ethanolic solution of novel monomethine cyanine dyes were measured and the antimicrobial activity of some selected monomethine cyanine dyes was discussed.     

Asymmetric Hydrogenation of 3‐Amido‐2‐arylpyridinium Salts by Triply Chloride‐Bridged Dinuclear Iridium Complexes Bearing Enantiopure Diphosphine Ligands: Synthesis of Neurokinin‐1 Receptor Antagonist Derivatives

We describe a most straightforward synthetic method for preparing neurokinin‐1 (NK1) receptor antagonist derivatives by asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts using dinuclear iridium complexes with enantiopure diphosphine ligands, affording the corresponding chiral piperidines in high cis‐diastereoselectivity (>95:5) and moderately high enantioselectivity (up to 86%). Deprotection treatments afforded the NK‐1 receptor antagonist (+)‐CP‐99,994 (83% ee). In addition, we observed unique additive effects of 10‐camphorsulfonic acid in the asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts.

     

Ring Transformations of 4,5- to the Isomeric 3,4-Disubstituted Isothiazolium Salts and their oxidation to 1,1-dioxides

4,5-Disubstituted N-phenyl-isothiazolium salts 1 with active 5-methyl group react under the influence of anilines to form 3,4-disubstituted isothiazolium salts 3 . The influence of donor and acceptor substituents in the 2-phenyl group of 1a–h and in the anilines 2 on the ring transformation were studied. The structure of the new salts was confirmed by X-ray analysis. The 3-hydroperoxy-2,3-dihydro-isothiazole 1,1-dioxides ( 12a,d ) and the isothiazole-3(2H)-one 1,1-dioxides ( 14a,d ) are obtained by oxidation of salts 3 with H₂O₂.     

Synthesis and structural assignment of certain pyrimido[1,2-a]benzimidazole derivatives

The pyrimido[1,2-a]benzimidazole derivatives compounds 1–8 were synthesized through cyclocondensation of 2-aminobenzimidazole with the appropriate benzsubstituted benzoylacetone by fusion at 150–170°C for 5 h. Quaternary salts compounds 9–22 were obtained by quaternization of compounds 1–8 with dimethyl or diethyl sulfate and subsequent isolation as the relatively insoluble perchlorate salts. Assignment and confirmation of the structures of the newly synthesized compounds were based upon elemental microanalyses and other spectral evidence.