α-Aminoalkylierungsreaktionen mit N-funktionellen Glyoxylsäurederivaten 5. Mitt.: α-Aminosäuren und Derivate

Aminoalkylation with Glyoxylic Acid Derivatives O.N- and N.N-Acetals as well as dialkylimoniumsalts of glyoxylic acid derivatives can be used for aminoalkylation of C-H-acid compounds, producing amides or esters of N.N-dialkylated α-aminoacids. The reaction is investigated on various examples.     

Lactone, 3. Mitt.1) Zur Synthese von α-Aminoalkyl-γ-lactonen

Lactones, III: Synthesis of α-Aminoalkyl-β-lactones Alkylation of α-acetyl-β-lactones with α-aminoethyl and -propyl chlorides, followed by in situ cleavage of the acetyl group with an excess of ethanolate is a general synthetic route to α-aminoethyl- and α-aminopropyl-β-lactones. The yields are limited by side reactions.     

Cyclophosphate, 8. Mitt. Synthese und Eigenschaften von 8-substituierten Adenosin-3′,5′-Phosphorsäure-benzylestern

Cyclophosphates, VIII: Synthesis and Properties of 8-Substituted Benzyl Adenosine-3′,5′-phosphates The 8-substituted adenosine-3′,5′-phosphates (cAMP) 2–12 were prepared by the substitution of bromine in 1 for various O, S, Se and N nucleophiles. pK_a Values of the products were measured spectrophotometrically. Compounds 2–12 were then esterified with phenyldiazomethane to yield the benzyl esters 13–23 . The diastereomeric mixtures of these 1,3,2λ⁵-dioxaphosphorinanes were separated chromatographically. Configurations were determined by ³¹P-NMR spectroscopy and were further substantiated by introducing ¹H-NMR chemical shift data as a new criterion. 8-Substituted benzyl cyclophosphates of this type offer themselves as lipophilic and cell penetrating cAMP derivatives for pharmacological purposes.     

Thion-und Dtihioester, 42. Mitt. Synthese und Eigenschaften von Thioncyanessigestern

Thiono and Dithio Esters, 42.- Synthesis and Properties of Cyanoacetic Thionoesters Malononitrile (1) can be transformed into the cyanoacetic thionoesters 3 via the imidoester 2 hydrochlorides 2 by thiolysis. The ethyl ester 3a condenses with benzylamine by H₂S elimination to form the imidoester 7 and with piperidine by elimination of ethanol to form cyanoacetic thioamide (9) . 3a reacts with equimolar amounts of phenyl hydrazine to give the hydrazonide ester 11 , which cyclises to the pyrazole 12 . With an excess of phenyl hydrazine the dihydro formazane 13 is formed. 13 can be oxidised by lead tetraacetate to give the formazane 14 and transformed by heat to the pyrazole 15 . Amidines were found to form with 3a the 4-amino-pyrimidines 17 and with the alkali salts of 3a the pyrimidine-4-thiones 18 . Amide acetals of aminal esters condense with 3a to yield the (dimethylaminomethylene)cyanoacetic thionoester 21 , which reacts with benzamidine to give the pyrimidine-5-carbonitrile 25 and with hydrazine to give the amino-pyrazole 27 .     

Dithio- und Thionester, 57. Mitt.: Synthese N-geschützter β- und γ-Aminosäuredithioester und -thionester

Dithio and Thiono Esters, LVII: Synthesis of Dithio and Thiono Esters of N-Protected β- and γ-Amino Acids The N-Protected β-aminonitriles 1 were transformed into the imidoester or thiolimidoester hydrochlorides 2 or 3 according to Pinner and sulfhydrolyzed with H₂S to give the N-protected β-amino thiono esters 4 or dithio esters 5 . Alkylation of the amides 6 and thioamides 7 yields the iminium salts 8/9 and their sulfhydrolysis again 4/5 . By the first approach N-protected γ-amino nitriles 11 were converted into the γ-amino thiono esters 14 and dithio esters 15 .     

Bicyclische α-Aminosäuren, 4. Mitt.1) Synthese von 3-(1-Tetralyl)- und 3-[5-(5,6,7,8-Tetrahydro)-chinolyl]-alanin

Bicyclic α-Amino Acids, IV: Synthesis of 3-(L1,2,3,4-Tetrahydro-l-naphthalenyl)- and 3-(5,6,7,8-Tetrahydro-5-quinolinyl)alanine The title compounds 1a , b are prepared by Strecker synthesis with the aldehydes 7a , b which are available from 2a , b . The structures of 1a , b and the configurations of the isomeric nitriles 3a , b / 4a , b were elucidated by ¹H- and ¹³C-NMR spectroscopy.     

Heterocyclisierungen an Ascorbinsäuren mit α, ß- ungesättigten Aldehyden und Ketonen, 2.Mitt.: Michael-Reaktionen von Ascorbinsäuren mit Acroleinderivatenstrukturelle und physikochemische Beobachtungen

Heterocyclisations of Ascorbic Acids with α, β-Unsaturated Aldehydes and Ketones, II: Michael Reactions of Ascorbic Acids with Acrolein Derivatives - Structural and Physicochemical Behaviour. The Michael reaction of ascorbic acids ( la – d ) with acrolein ( 2 ) and some derivatives ( 7 , 8 ) is reported. The pH-optimum of the reaction course is 4. Furthermore, solvents supporting ionisation are favourable. α- and β-subsituted acrolein derivatives react differently: Crotonaldehyde, a β-substituted derivative, reacts nearly quantitatively to the spiro compounds 3e and 3f , whereas α-ethyl-acrolein favours the formation of 4g and 4h .     

Indole, 10. Mitt.: Synthese,Struktur und D2-Affinität des β-Carbolin-Analogons von Flutrolin

Indoles X: Synthesis, Structure and D₂-Affinity of the β-Carboline-Analogue of Flutroline 10 is a β-carboline analogue of the neuroleptic flutroline^2a,b) with significant lower affinity at the dopamine D₂ binding site. Various synthetic routes to 10 and the solid state structure of 8 are described, structure activity relations, in particular the importance of the “S-shape” and the rigid dopamine conformation are discussed.     

Synthesen und Reaktionen von Pyridazinderivaten, 18. Mitt.1) Synthese neuer halogenhaltiger 5-Aroyl-4-pyridazin-carbonsäuren und Phenyl-4-pyridazinylketone

Syntheses and Reactions of Pyridazine Derivatives, XVIII: Synthesis of Novel Halogen Containing 5-Aroylpyridazine-4-carboxylic Acids and Phenyl 4-Pyridazinyl Ketones The ketocarboxylic acids 4c-h were prepared by Minisci-reaction of ethyl pyridazine-4-carboxylate, followed by alkaline hydrolysis of the resulting esters 2. Compounds 4 are also obtained by homolytic aroylation of pyridazine-4-carboxylic acid. The hitherto unknown aryl 4-pyridazinyl ketones 5c, d, f, g, h were prepared by decarboxylation of the carboxylic acids 4.     

H2-Antihistaminika, 2. Mitt. Synthese und Pharmakologie α-substituierter Metiamid-Analoga

H₂-Antihistaminics, II: Synthesis and Pharmacology of α-Substituted Metiamide Analogues The synthesis of α-substituted 5-methyl-4- {2-[3-(methyl)thioureido]ethylthiomethyl}-1H-imidazoles 4 from α-substituted 4-methoxymethyl-5-methyl-1H-imidazoles 2 is described. The H₂-antihistaminic activity of the products is reported.     

β-Lactame und β-Lactam-Zwischenprodukte, 2. Mitt.: Stereoselektive Synthese von cis-3-Amino-1,4-diphenyl-azetidin-2-on

β-Lactams and β-Lactam-Intermediates, II: Stereoselective Synthesis of cis-3-Amino-1,4-diphenyl-azetidin-2-one Phthalylglycyl chloride ( 1 ) reacts with benzalaniline ( 3 ) in the presence of triethylamine to yield 1,4-diphenyl-3-phthalimido-azetidin-2-one ( 5 ). The selectivity of formation of cis-β-lactam 5 was improved considerably by decreasing the concentration of chloride in the reaction-solution and by lowering of the temperature. Hydrazinolysis of 5 yields 3-amino-1,4-diphenyl-azetidin-2-one ( 8 ).     

Bicyclische α-Aminosäuren, 2. Mitt. Zur Synthese von 3-(1-Tetralyl)- und 3-[5-(5,6,7,8-Tetrahydro)-chinolyl]-alanin

Bicyclic α-Amino Acids, II. On the Preparation of 3-(1-Tetralyl)-and 3-[5-(5,6,7,8-Tetrahydro)quinolyl]alanine Carbonyl olefination of the tetralones 4 does not yield the expected compounds 6 but the isomeric acetic acid derivatives 7 with endocyclic double bond, from which the ketoesters 10 can be prepared via intermediates 8 and 9 . Saponification of 9 and 10 fails to yield the α-ketoacids 11 and 12 .     

Synthese von Phosphorsäurephenylesterdiamiden, 1. Mitt.

Synthesis of Phenyl Phosphorodiamidates, I Two procedures are described for the synthesis of phenyl phosphorodiamidates in high yields. These compounds can be represented by the general formula 6 and are used for cyclisation reactions leading to phosphabarbituric acids.     

Bicyclische α-Aminosäuren, 3. Mitt. Zur Synthese von 2-(1-Tetralyl)- und 2-[5-(5,6,7,8-Tetrahydro)-chinolyl]-glycin

Bicyclic α-Amino Acids, III: On the Preparation of 2-(1,2,3,4-Tetrahydronaphthalen-1-yl)- and 2-(5,6,7,8-Tetrahydroquinoline-5yl-)glycine Attempted halogenation of 2 does not yield the expected bromo(1,2,3,4-tetrahydronaphthalen-1-yl)acetic acid 4 but the cyclic ketone 3 . The α-ketoesters 5 can be decarbonylated to yield the substituted malonic esters 6 . Compounds 6a and 7a react with isopropyl nitrite to yield the oximinocarboxylic acid 8a which can be hydrogenated at room temperature to yield the title compound 9a . Hydrogenation at 80° C leads to the decalylamino acid 10a . The analogous sequence of reactions ( 6b and 7b→8b→9b ) fails to yield tetrahydroquinolinylglycine 9b .     

Cer(IV)oxidationen von β–Aminoketonen. 7. Mitt.: Synthese von 4-Benzoylisochinolin und des davon abgeleiteten Lactams

Cerium(IV) Oxidations of β-Aminoketones. Part 7: Synthesis of 4-Benzoylisoquinoline and of the Corresponding Lactame     

Über die Synthese von o-Acylamino-β-dimethylamino-propiophenonen 2. Mitt.: Aminomethylierung von o-Carbäthoxyamino- und o-Nitro-acetophenon1)

Synthesis of o-Acylamino-β-dimethylamino-propiophenones The reaction between formaldehyde and aminomethylation products of o-carbethoxyamino-and o-nitro-acetophenone leading to acrylophenone derivatives could be avoided in the following way: by blocking the decomposition of the intermediary resulting dimethylaminomethylol in its components, the formation of the carbonium-imonium-cation was accelerated and free formaldehyde necessary for the reaction was quickly eliminated from the reaction mixture. — The synthesis of o-carbethoxyamino-, o-nitro- and o-amino-β-dimethylamino-propiophenone and its formyl and acetyl derivatives is described.     

Synthese und Eigenschaften von 2-Hydroxycarbohydroximsäure-estern

Synthesis and Properties of 2-Hydroxy Carbohydroximic Esters Sulfhydrolysis of the glycolimidates 4 affords 2-hydroxy thiocarboxylic O-esters 5 , which on treatment with hydroxylamine give 2-hydroxy carbohydroximic esters 3 . The (E)/(Z) isomer distribution of 3 depends largely on the substituents at C-2 and can be affected by UV irradation which produces more of the (E) isomer.