Reaktionen von N-Alkoxycycliminiumsalzen, 13. Mitt.1) Reaktionen nitrosubstituierter 2-Chlor-N-methoxy-pyridiniumsalze mit Carbanionen

Reactions of N-Alkoxycycliminium Salts, XIII: Reactions of Substituted 2-Chloro-N-methoxypyridinium Salts with Carbanions As with N-bases, the pyridinium salts 1a and 1c also react with ambident CH-acidic compounds. While 1a is attacked at C-6 and reacts by ring cleavage to give the polyene derivatives 2 , the salt 1c forms the 2-substituted pyridinium compounds 5 by nucleophilic substitution of the chlorine atom.     

Reactions of N-alkoxycycliminium salts, VIII: reactions of N-methoxypyridinium salts with aromatic amines and sulfonamides. (author's transl)

Reactions of N-Alkoxycycliminium Salts, VIII: Reactions of N-Methoxypyridinium Salts with Aromatic Amines and Sulfonamides. The 1-(methoxyimino)pentadienes 2 - 12 are prepared by reaction of N-methoxypyridinium salts 1 with aromatic amines and sulfonamides in dipolar aprotic solvents. Some reactions require the presence of a base. The u.v., i.r. and n.m.r. spectra of the products are discussed.     

Reaktionen von N-Alkoxycycliminiumsalzen, 10. Mitt. Zur Stabilität von 2-Chlor-N-methoxy-nitropyridiniumsalzen in polaren Solventien

Reactions of N-Alkoxycycliminium Salts, X: Stability of 2-Chloro-N-methoxy-nitropyridinium Salts in Polar Solvents Nitro substitution of the pyridine ring of 2-chloro-N-methoxypyridinium ions remarkably enhances the electrophilicity of these compounds. In polar and dipolar aprotic solvents, e.g. DMF and DMSO, the pyridinium salts 2a and 2c react spontaneously to yield the 2-pyridones 3a and 3c , even at room temperature. Similar reactions of the 4-nitro isomer 2b yield mixtures of 2- and 4-pyridones but, compared with 2a and 2c , the reactivity is markedly decreased.     

Reaktionen von N-Alkoxycycliminiumsalzen, 11. Mitt.1) Reaktionen von 2-Chlor-N-methoxy-3-(-4)-nitropyridinium-(perchlorat) mit Aminen

Reactions of N-Alkoxycycliminium Salts, XI: Reactions of 2-Chloro-N-methoxy-3-or-4-nitropyridinium Perchlorate with Amines Reactions of 3-, 4- and 5-nitro-2-chloro-N-methoxypyridinium salts with aromatic and aliphatic amines show a remarkable dependence with regard to reactivity and pathway on the position of the nitro group. While reactions of the 3-nitro derivative 1a are characterized by attack at position 6 of the pyridine ring followed by ring cleavage yielding stable 1-methoxyimino-2,4-pentadiene derivatives, reactions of the 4-nitro compound 1b are more complex and the reactivity is remarkably decreased.     

Untersuchungen an 1,3-Thiazinen, 41. Mitt.: Iminiumkohlensäurederivat-Salze, 5. Mitt.1): Vilsmeier-artige Reaktionen mit N-substituierten 2-Chlor-5,6-dihydro-4H-1,3-thiaziniumsalzen

Investigations on 1,3-Thiazines, XLI¹); Iminium Carbonic Acid Derivative Salts, V¹): Vilsmeier-Type Reactions with N-Substituted 2-Chloro-5,6-dihydro-4H-1,3-thiazinium Salts The strongly electrophilic N-substituted 2-chloro-5,6-dihydro-4H-1,3-thiazinium salts 1 react in a Vilsmeier-type reaction with pyrrol derivatives and indol to yield the surprisingly stable salts 2–4 .     

Mechanismus der selektiven Bildung von 2-aminosubstituierten 1,4-Benzodiazepin-4-oxiden und 2-aminomethylsubstituierten Chinazolin-3-oxiden aus Chlormethyl-chinazolin-N-oxiden Störungstheoretische Befunde

Mechanism of Selective Formation of 2-Amino-substituted 1,4-Benzodiazepin-4-oxides and 2-Aminomethyl Substituted Quinazolin-3-oxides from Chloromethyl Quinazolin-N-oxides Indications from Perturbation Theory The o-amino-acetophenone and -benzophenone oximes 1a-c react with chloroacetyl chloride giving the 2-chloromethyl-quinazoline-3-oxides 6a-c . The mechanism is explained using the perturbation theory. With ammonia and N-prim. aliphatic amines, compounds 6a-c yield 1,4-benzodiazepines 16 and 17 as ring-enlarged products, with aromatic and with N-sec. aliphatic amines, quinazoline derivatives 10–13 are formed. The constitution of the heterocycles is proved by nmr spectroscopic methods. Selective formation of the heterocyclic products is explained with the relative thermodynamic stability of the corresponding 2-adducts 14 .     

Reaktionen von N-Alkoxycycliminiumsalzen, 12. Mitt.1) Reaktionen von 2-Chlor-N-methoxy-5-nitropyridinium-(-perchlorat) mit aliphatischen und aromatischen Aminen

Reactions of N-Alkoxycycliminium Salts, XII: Reactions of 2-Chloro-N-methoxy-5-nitropyridinium Perchlorate with Aliphatic and Aromatic Amines Reactions of the 2-chloro-N-methoxy-5-nitropyridinium compound 1c with primary and secondary amines show a remarkable dependence on the basicity of the applied reagents. Reactions with aliphatic amines are characterized by attack at position 6 of the pyridine ring followed by ring cleavage to yield 1-methoxyimino-2,4-pentadiene derivatives, whereas reactions with less basic amines, e.g. aniline derivatives, lead to 2-substituted pyridine derivatives.     

Untersuchungen an 1,3-Thiazinen, 38. Mitt.: Iminiumkohlensäurederivat-Salze, 2. Mitt.: Synthese N-substituierter 2-Chlor-5,6-dihydro-4H-1,3-thiazinium-salze und deren Reaktionen mit primären Aminoverbindungen

Synthesis of N-Substituted 2-Chloro-5,6-dihydro-4H-1,3-thiazinium Salts and Their Reactions with Primary Amino Compounds After a short review of synthesis and reactions of halogeno(organothio)methaniminiumsalts, the reactions of tetrahydro-1,3-thiazine-2-thiones 9 with thionyl chloride or phosgene to yield 2-chloro-5,6-dihydro-4H-1,3-thiazinium chlorides 10 are described. Compounds 10 can be converted to the more stable tetrafluoroborates 13 and hexafluorophosphates 12 , which can be conveniently characterized. Chloroiminium chlorides 10 generated in situ, react with primary amino compounds such as aliphatic or aromatic amines, carboxamides, sulfonamides, diphenylphosphinamide, cyanamide or N-substituted ureas to yield the N,N′-disubstituted 2-iminotetrahydro-1,3-thiazines 17 – 24 .     

Untersuchungen an 1,3-Thiazinen, 36. Mitt. Aminierung von Salzen NH-acider Tetrahydro-1,3-thiazinderivate mit O-Diphenylphosphoryl-hydroxylamin

Investigations on 1.3-Thiazines, XXXVI; Amination of Salts from NH-acidic Tetrahydro- 1.3-thiazinederivatives with O-Diphenylphosphoryl-hydroxylamine NH-acidic 2-thioxo-4-oxo- or 2,4-dioxo-1,3-thiazine derivatives 3 or 5 were converted into their sodium-or thallium(I)-salts 4 and 6 , which were reacted with O-diphenylphosphoryl-hydroxylamine to yield the S-amination product 9 or the N-amination product 10. The N-amino-2-thioxo-thiazine 2, which could not be obtained in this way, resulted from cyclization of 1.     

Untersuchungen in der Reihe der N1-Hydroxyamidine: Synthesen und Umsetzungen mit Isocyanaten und 1,1′-Carbonyl-diimidazol

N¹-Hydroxyamidines: Syntheses and Reactions with Isocyanates and 1,1′-Carbonyldiimidazole Reactions of N²-unsubstituted N¹-hydroxyamidines 3, 4 with isocyanates lead to open-chain products. Ring closure to 7 does not occur. Treatment with 1,1′-carbonyldiimidazole yields the cyclic products 8, 9 . Formamidine derivatives with N²-substitution give the 1-amidinoimidazoles 17 , which can be regarded as addition products of carbodiimides 16 and imidazole.     

Chirale 3-Aminopropanole, 2. Mitt. N-Alkylierungsprodukte

Chiral 3-Aminopropanols, II: N-Alkylated Products From the racem. and optically active 3-aminopropanols 1a-1d the N-monomethyl compounds 3 are obtained via the urethanes 2 . Methylation of 1a-1d according to Eschweiler-Clarke or reaction with formaldehyde/NaBH₃CN yield the N-dimethyl compounds 4 . With acetone/NaBH₄ 1a-1d react to give the N-isopropyl compounds 6 .     

Heterocyclische 12-π- und 14-π-Systeme, 21. Mitt. Zum Reaktionsverhalten von 2-Äthyl-3-formyl-5-methylbenzofuran

Heterocyclic 12-π and 14-πSystems, XXI: Reactions of 2-Ethyl-3-formyl-5-methylbenzofurane 2-Ethyl-5-methyl-benzo[b]furane (1) reacts with Vilsmeier reagent to yield 2-ethyl-3-formyl-5-methylbenzo[b]furane (2) which reacts with N-nucleophiles to give compounds 3a–3c . With C-nucleophiles derivatives 4a–4g are obtained.     

Thiocyanatocarbonsäurehydrazide und ihre Isomerisierungsprodukte, 1. Mitt.: Synthesen von Derivaten des 3-Amino-2-thiohydantoins

Thiocyanatocarboxylic Hydrazides and Their Isomerization Products, I: Syntheses of 3-Amino-2-thiohydantoin Derivatives The reaction of α-chlorocarboxylic N²,N²-dialkyl-, alkyl-aryl- or diaryl hydrazides 1 with potassium thiocyanate in acetonitrile proceeds via thiocyanates and isothiocyanates 2 and 3 , respectively, to yield the 3-amino-2-thiohydantoins 5 . Methylation of these products leads to derivatives of the 1 -amino-2-methylthioimidazolinone 4 .     

Selektive katalytische Hydrierungen und Hydrogenolysen, 5. Mitt. Ein einfacher Zugang zu 1-Benzyl-5,6,7,8-tetrahydroisochinolinen

Selective Catalytic Hydrogenations and Hydrogenolyses, V: Convenient Preparation of 1-Benzyl-5,6,7,8-tetrahydroisoquinolines 1-Benzylisoquinolines 1 can be hydrogenated selectively with Pt and Ru catalysts to yield the title compounds 2 . Using Pd/charcoal, the products 2 contain ca. 5% of the isomers 3 , which can be separated via the N-acetyl derivatives, e. g. 7d . Extended reaction times in the presence of platinum cause simultaneous hydrogenation of the unsubstituted aromatic nucleus of the benzyl group. At higher temperatures, the substituted benzyl nucleus is hydrogenated, too, involving C,O-hydrogenolysis, e. g. 1a → 4 or 1d → 4 . The structures of 2 were proved by ¹H-NMR spectroscopy. Compound 2a was prepared independently from 2c via 5 → 6 .     

Ringschlußreaktionen mit N-(Chlormethyl)carbimidoylchloriden, 1. Mitt. Synthesen von Dihydro-1,3,5-triazin-derivaten

Heterocyclisation Reactions with N-(Chloromethyl)carboximidoyl Chlorides, I: Syntheses of Dihydro-1,3,5-triazines N-(Chloromethyl)benzimidoyl chloride ( 1 ) reacts with benzamidine, 2-aminopyridine or 2-aminobenzothiazole to yield the dihydro-1,3,5-triazine derivatives 2 , 3 and 4 whose ¹³C-NMR spectra were used to determine the structures.     

Iminiumkohlensäurederivat-Salze, 7. Mitt. Teil I: Elektrophile Reaktionen von 2-Methylthio-5,6-dihydro-4H1,3-thiaziniumiodiden, 2-Methylthio-4,5-dihydrothiazoliumiodiden und 2-Methylthio-5-methylthiazoliumiodiden mit N-Nucleophilen

Iminium Carbonic Acid Derivative Salts VII, Part I: Electrophilic Reactions of 2-Methylthio-5,6-dihydro-4H-1,3-thiazinium Iodides, 2-Methylthio-4,5-dihydrothiazolium Iodides, and 2-Methylthio-5-methylthiazolium Iodides with N-Nucleophiles Cyclic salts of the dithiocarbonic acid diester imidium type ( 3, 5 ) react with NH₂-nucleophiles to the cyclic isothioureas 6 – 8 . Some of these compounds were oxidized to cyclic isothiourea-S,S-dioxides ( 9, 10 ).     

Degradation reactions of oral antidiabetics. 1. Reactions of arylsulfonylurea compounds with carboxylic acid anhydrides

Degradation of Oral Antidiabetics, 1: Reactions of Arylsulfonylureas with Carboxylic Acid Anhydrides The arylsulfonylureas 1a–h were reacted with carboxylic acid anhydrides in pyridine. By acetic anhydride, compounds 1 were cleaved rapidly to the N-(arylsulfonyl)acetamides 2 and N-alkylacetamides 3 . In contrast, phthalic anhydride prompted a slow reaction yielding mixtures of N-(arylsulfonyl)phthalimides 9 , arylsulfonamides 10 and N-alkylphthalimides 11 . The ratio of the products formed depends on the reaction time. In the presence of catalytic amounts of DMAP, only 10 and 11 were obtained. Depending on the structure of compounds 1 , treatment with succinic anhydride led to succinic diamides 17 , arylsulfonamides 10 and N-alkyl-succinimides 18 , or N-(arylsulfonyl)succinimides 19 .     

Aromatic Oxidation of Some Phenothiazines

1. The previously reported N-oxidation products phenothiazine-N-OH, N-O and -NOOH obtained upon chemical and metabolic oxidation of phenothiazine nuclei are now shown to be the C-oxidation products, 7-hydroxyphenothiazines, phenothiazin-3-ones and phenothiazin-7-ones which have the para-hydroquinoneimino and para-quinoneimino type systems.

2. The metabolism of various 2-substituted phenothiazines in vitro gave mainly ring-hydroxylated metabolites and sulphoxides. The phenolic metabolites were further oxidized to phenothiazones either as metabolites or as ‘metabonates'.

3. After metabolism of chlorpromazine, nor₁-chlorpromazine and nor₂-chlorpromazine in vitro, phenothiazones (‘pink compounds’) were obtained as N-dealkylated products of the phenolic derivatives 7- or 3-hydroxy compounds.

4. The synthesis and physicochemical characteristics including t.l.c., u.v., g.l.c. and mass spectra of the oxidized phenothiazine nuclei and of 8-(N-methylanilmo)-2-chlorophenothiazin-7-one are reported.

5. It is postulated that in metabolism one electron is transferred from a region of high electron availability (positions 3 and/or 7) in the molecule to activated oxygen to give the phenolic derivatives.     

Untersuchungen an 1,4-Naphthochinonen, 23. Mitt.1): 2/3-Halogen-2/3-nitrophenyljuglonderivate,Synthese und cytotoxische Eigenschaften

1,4-Naphthoquinones, XXIII: 2/3-Halogeno-2/3-nitrophenyl-juglone Derivatives, Synthesis and Cytotoxic Properties Radical arylation of 1,4-naphthoquinones is possible by oxidative decarboxylation of 2- and 4-nitrobenzoic acid. With 2- and 3-halogenojuglone derivatives the 4-nitrophenyl compounds 10–13 are prepared in good, the 2-nitrophenyl analogues 14–17 only in poor yields. - All compounds are inactive against the virus types HSV and HIV and their marked cytotoxicity in part depends on the substitution pattern. The 3-aryl and o-nitro derivatives are more active than their 2-aryl and p-nitro analogues and the influence of the chloro or bromo substitution is only remarkable in the case of 12/13 .     

Untersuchungen an 1,3-Thiazinen, 42. Mitt.: Carbazoylierungen und Thiocarbazoylierungen von 2-Thioxo-tetrahydro-1,3-thiazin-Derivaten

Investigations on 1,3-Thlazines, XLII¹⁾: Carbazoylations and Thiocarbazoylations of 2-Thioxo-tetrahydro-1,3-thiazine Derivatives⁺⁾ Carbazic acid chlorides react with 2-thioxo-tetrahydro-1,3-thiazines 6 and 7 yielding N-Carbazoyl-thiazine derivatives 9 and 11 . Thiocarbazic acid chlorides attack under kinetic control at the 2-thioxo sulfur yielding S-substitution products 10 and 12 , which can thermally be rearranged intramolecularly to the more stable N-substituted products 9 and 11 .