Azidiniumsalze. 22. Mitteilung. über 3-äthyl-2-tetrazo-6-X-benzo[d]thiazoline und ihre Reaktivität: Ein Beitrag zur Chemie nucleophiler Carbene

3-Ethyl-2-tetrazo-6-X-benzo[d]thiazolines and Their Reactivity: A Contribution to the Chemistry of Nucleophilic Carbenes The synthesis of 3-ethyl-2-tetrazo-6-X-benzo[d]thiazolines 3 - a new class of azohomologous diazo compounds - by addition of azide ions to azidinium salts 4 is described, their structure and some of their reactions are disscussed. The thermolysis of 3 at ca. 270 K in DMFA or THF generates nucleophilic carbenes 1 , whose trapping by electrophilic compounds such as 3 , 4 , diazonium salts, diazo compounds, methanol, sulfur and tetracyanoethylene could be studied. Direct dimerisation of 1 to 2 (without acid/base catalysis) could not be found, as demonstrated by the behavior of 1e .     

Enantioselektive α-Alkylierung von Asparagin- und Glutaminsäure über die Dilithium-enolatocarboxylate von 2-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]essigsäure und 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionsäure

Overall Enantioselective α-Alkylation of Aspartic and Glutamic Acid through Dilithium Enolatocarboxylates of 2- [3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]acetic and 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionic Acid, respectively The pure methyl esters 10 of the heterocyclic carboxylic acids specified in the title were prepared in several steps by known methods from aspartic and glutamic acid, with overall yields of ca. 20%. The corresponding heterocyclic acids 11 were doubly deprotonated by LiNEt₂/BuLi or LiN(i-Pr)₂/BuLi to give enolatocarboxylates ( 3 ). The latter were reacted with electrophiles (MeOD, Mel, C₆H₅CH₂Br) to give the crystalline products 14 – 21 diastereoselectively. Hydrolysis of the imidazolidinone ring of three such products gave the corresponding α-branched aspartic and glutamic acids 22 – 24 of known absolute configuration, thus establishing the stereochemical course of the overall enantioselective alkylations.     

Darstellung und Eigenschaften von Tris-(β-chloräthyl) phosphinoxid und Bis-(β-chloräthyl)-(chlormethyl)-phosphinoxid. 43. Mitteilung über organische Phosphorverbindungen [1]

The oxidative degradation of [(HOCH₂CH₂)₃PCH₂OH]⁺Cl^? ( 1 ) with Cl₂ yields, dependent on the pH used, either (HOCH₂CH₂)₃P?O ( 2 ) or (HOCH₂CH₂)₂ (HOCH₂) P?O ( 3 ). Chlorination of 2 and 3 with PCl₅ produces the corresponding chlorides (ClCH₂CH₂)₃P?O ( 4 ) and (ClCH₂CH₂)₂ (ClCH₂)P?O ( 5 ), respectively. Acetylation of 2 and 3 gives the corresponding esters (CH₃CO₂CH₂CH₂)₃P?O ( 6 ), and (CH₃CO₂CH₂CH₂)₂ (CH₃CO₂CH₂)P?O ( 7 ), respectively. Reaction of 7 with HBr results in the formation of (BrCH₂CH₂)₂ (BrCH₂)P?O. Nucleophilic substitution of the chlorine atoms in 4 and 5 with alkoxide or mercaptide gives e.g., 9 , 10 , 11 or 11a , while treatment with tertiary amines yields the vinyl compounds (CH₂?CH)₃P?O ( 12 ) and (CH₂?CH)₂ (CH₂Cl)P?O ( 13 ). 4 and 5 also undergo an Arbuzov type reaction with tertiary phosphites to give 14 and 15 , respectively, which on hydrolysis with conc. HCl give the corresponding acids 16 and 17 , respectively.     

Zum Einfluß der Ringgröße auf die Struktur von Metallchelaten dreizähliger Liganden. I. Kupfer(II)- und Zink(II)-Chelate des Bis[ß-(pyridyl-2)-äthyl]-amins und des [ß-(Pyridyl-2)-äthyl]-[(pyridyl-2)-methyl]-amins

The Influence of Ring Size on the Structure of Metal Chelates with Tridentate Ligands. I. Copper(II) and Zinc(II) Chelates of Bis[β-(pyridyl-2)ethyl]amine and [β-(Pyridyl-2)-ethyl] [(pyridyl-2)methyl]amine The tridentate ligands 2.3-py₂tri and 3.3-py₂tri form 1,1-complexes with copper(II) salts, having the coordination numbers 5 or 6. The less bulky ligand 2,3-py₂tri is also tridentate in the 1,1-complexes of zinc. But 3,3-py₂tri in combination with polarisable anions like chloride, bromide, or iodide induces a tetrahedral structure in complexes of this type. One of the pyridine donor atoms remains non-coordinated. Using 2,3-py₂tri in excess, 1,2-complexes may be prepared both of copper(II) and of zinc (II) With 3,3-py₂tri under the same conditions oligomeric hydroxy complexes [Cu(3,3-py₂tri)(OH)Y]_n and Zn₂(3,3-py₂tri)₂(OH)(ClO₄)₃, or binuclear compounds like Cu₂(3,3-py₂tri)(ClO₄)₄ are formed. In the latter case a part of 3,3-py₂tri has the function of a bridging ligand. In spite of the lower basicity and of the stiffening by heteroatomatic rings there are close relations between 2,3-py₂tri or 3,3-py₂tri and the aliphatic amine ligands 2,3-tri and 3,3-tri.     

Innerkomplexe mit Metallamidbindungen. II. Zink- und Chrom(II)-Komplexe des 2-[β-(Phenyl-amino)-äthyl]-pyridins

The preparation of uncharged complexes with metal amide bonds of type [MeN₄]^±0 (Me = Zn²⁺, Cr²⁺ is reported. These compounds are obtained by the interaction between Zn(C₆H₅)₂ or Cr(C₆H₅)₃ · 3 THF and 2-[β-(phenyl-amino)-ethyl]-pyridine (I). The same complexes are formed by the reaction between ZnCl₂ · 2 THF, CrBr₂ · 2 THF, or CrCl₃ · 3 THF and the lithium amide (II), which is prepared from (I) and phenyl lithium. The structure of the chromium(II) complex is discussed on the basis of magnetic and visible absorption measurements.     

Die Chemie des Wieland-Gumlich-Aldehyds und seiner Derivate [1] 136. Mitteilung über Alkaloide [2]

The course of the reactions involved in the process of degradation of strychnine ( 1 ) to Wieland-Gumlich aldehyde (WGA) ( 2 ), first performed by Wieland, Kaziro & Gumlich , has been elucidated. 23-Isonitrosostrychnine hydrochloride ( 9a ) upon treatment with thionyl chloride undergoes a fragmentation (2nd order Beckmann rearrangement), thus furnishing N(a)-cyanoformyl-WGA hydrochloride ( 14a ). On heating in an acidic medium, the latter compound is transformed — at least partially via the cyclic urethane 15 — into WGA ( 2 ), which is an important keyintermediate in the syntheses of strychnine and curare alkaloids. The compound 2 can now be obtained in high purity and good yield. A corresponding degradation has been realized with quaternary analogues ( 27 → 3 ) as well as with 10-chlorostrychnine ( 58 → 62 ). 10-Chlorostrychnine ( 58 ) was prepared by chlorination of strychnine with chlorine in conc. hydrochloric acid according to Leuchs & Steinborn. As by-products of the reaction, 10, 15-dichlorostrychnine ( 59 ) and 10, 15, 19-trichlorostrychnine ( 60 ) could be identified. Starting from WGA a series of derivatives have been prepared. Special mention is made of the two epimeric methyl ethers 18 and 19 . The absolute configuration at the centre 17 of WGA and of these two substances has been established by optical comparisons of 3 epimeric pairs. The methyl ether 18 , by-product « B », is obtained if methanol is used in working up the Beckmann rearrangement products of 23-isonitrosostrychnine hydrochloride ( 9a ). A second by-product, « A », results by working up under alkaline conditions. This compound has the structure 44 with inverted configuration at centre 16. Degradation of 44 under controlled conditions leads either to WG-diol ( 42 ) or to 16-epi-WG-diol ( 51 ). Besides « A z.rdang; and « B » a series of by-products and intermediates ( 16, 17, 11a, 22. 23, 24 and 25 ) could be detected in the course of the process of strychnine degradation.     

Potential antidepressants. Synthesis of 6,11-dihydrodibenzo[b,e]thiepin-11-yl 4-(dimethylamino-methyl)phenyl ketone and of some related compounds

Reactions of dibenzo[b,e]thiepin-11(6H)-one (4) with 2-, 3- and 4-(dimethylaminomethyl)phenylmagnesium bromide afforded the tertiary alcohols 5a,b,c. The aldehydes 7 and 8 gave similarly the secondary alcohols 9a,b,c and 10c . Numerous attempts to prepare the corresponding ketones, especially by oxidation of 9a,b,c and 10c were unsuccessful. Only the oxidation of 9c with tetrabutylammonium chromate in chloroform afforded the desired ketone 16 . Its formation was accompanied by an important side reaction consisting in a cleavage of the “retro-ene-reaction” type leading to compound 11 and the aldehyde 13c which reacted with the chloroform present to give the alcohol 17 . Compounds 5a,b,c, 9a,b,c and 16 were tested as potential antidepressants but with the exception of some effects in the test of potentiation of yohimbine toxicity in mice, they proved inactive in this line.     

Methylierung von 4-Hydroxy-4-(2-piperidyl)-4H-pyrazolo [1,5-a]indol mit Formaldehyd und Ameisensäure. 11. Mitteilung über metallorganische Reaktionen und Folgeprodukte

In the 10^th communication of this series [1] the synthesis of 4-hydroxy-4-(2-piperidyl)-4H-pyrazolo[1,5-a]indole ( 4 ) was described (Scheme). Surprisingly enough, methylation of this compound with formaldehyde and formic acid led via ring closure and a subsequent rearrangement to a pentacyclic ketone. By means of ¹³C-NMR.-spectroscopy and mass spectroscopy, this ketone could be identified as a indolizino-pyrazolo-indole ( 9 ). Its structure and configuration were determined by X-ray structure analysis.     

Synthesis of 1-[3-methyl-2(3H)-benzazolon-5- or 6-yl]-4-{4-[cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl-methyl)-1,3-dioxolan-4-yl]methyleneoxyphenyl}piperazines

Reactions of 3-methyl-6-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzoxazolone, 3-methyl-6-[4-(4-hydroxy-phenyl)-1-piperazinyl]-2(3H)-benzothiazolone and 1,3-dimethyl-5-[4-(4-hydroxyphenyl)-1-piperazinyl]-2(3H)-benzimidazolone with cis-{[2-(2,4-dichlorophenyl) -2-(1H-imidazol-1-ylmethyl)]-1,3-dioxolan-4-yl}methyl meth-anesulfonate in the presence of sodium hydride furnish the title compounds.     

Synthesis of 5,6-dimethoxythiophen-3H(2)one and 6,7-dimethoxythiochroman-2-one. Derivatives of tetramethoxy-10,11-dihydrodibenzo[β,f]thiepin-10-one

Reduction of 4,5-dimethoxy-2-carbomethoxymethylbenzenesulfonyl chloride and 4,5-dimeth-oxy-2-carboethoxyethylbenzenesulfonyl chloride with zinc, hydrochloric acid, produced the corresponding o-mercapto-aeids which then cyclized to thiaindanone and thiochromanone, respectively. Thiaindanone and thiochromanone reacted readily with aniline to give 4,5-dimeth-oxy-2-mereaptophenyl-N-phenylacetamide and 4,5-dimethoxy-2-mercaptophenyl-N-phenylpropyl-amide. Mercaptophenyl N-phenylacetamide yielded in two steps the 4,5-dimethoxy-2-N-phenyl-acetarnido(3′,4′ -dimethoxyphenylthio)benzene, which was cyclized to the 2,3,7,8-tetramethoxy-10,11-dihydrodibenzo[b, f]thiepin-10-one. Reduction of thiepinone with sodium borohydride leads to the corresponding alcohol.     

Chinazolincarbonsäuren. XII. Mitteilung. Synthese von [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxochinazolin-3-yl]-, [2-(Ethoxycarbonyl)chinazolin-4-yloxy]- und (5,6,7,8-Tetrahydro-2-phenylchinazolin-4-ylthio)alkansäure-estern

Quinazolinecarboxylic Acids. Synthesis of Alkyl [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-yl]-, [2-(Ethoxycarbonyl)quinazolin-4-yloxy]- and (5,6,7,8-Tetrahydro-2-phenylquinazolin-4-ylthio)alkanoates The [(2-aminobenzoyl)amino]alkanoic acids and their esters 1 showed a different reaction behaviour with diethyl oxalate. Compound 1 (n = 2,3) was converted into the quinazolinylalkanoates 3 . o-Aminohippurate yielded with ethyl (chloroformyl)formate a mixture of the amide 4 and the cyclized quinazolinone 7b . Ethyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate ( 6 ) reacted with 2-bromoalkanoates, in the presence of NaH, to the [2-(ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-y1]acetates 7 in the case of alkyl bromoacetate, and to the O-alkylated derivatives 8 with the ethyl 2-bromopropionate and -butyrate. 2-Aminobenzamide ( 5 ) gave with ethyl 3-(chloroformyl)-2-propenoate and methyl 3-(chloroformyl)propionate the amides 9 or 11 , respectively, and not the expected quinazolinones. The cyclized product 12 was obtained from 11 and ethyl bromoacetate. Tetrahydroquinazolin-4(3H)-thione 14 was synthesized by the reaction of 13 with NH₃, and it was alkylated at the S-atom with bromoalkanoates to 15 . The hydrazide 16 was synthesized from 15b with hydrazine hydrate.     

Salze der Tris[1,2-äthandiolato(2-)]- und der Tris[2,3-butandiolato(2-)]arsensäure

Salts of the Tris[1.2-ethanediolato(2-)]- and of the Tris[2.3-butanediolato(2-)] Arsenic Acid Salts of tris[1.2-ethanediolato(2-)]arsenic acid and of tris[2,3-butanediolato(2-)]-arsenic acid are obtained by ester interchange of As(OCH₃)₅ with 1.2-diols in the presence of various amines.     

Konfigurative Zusammenhänge in der Muscarinreihe; Chiralität des epi-, allo- und epiallo-Muscarins,des Muscarons und allo-Muscarons. Zur biogenese des muscarins 37. Mitteilung über muscarin und verwandte stoffe

The chirality of all stereoisomeric muscarines has been determined. (–)-Muscarine chloride was converted to (+)-normuscarine, which in turn was oxidized to (+)-normuscarone. Epimerisation by acid catalysis of the latter gave a mixture of the C(2)-epimers, namely (+)-normuscarone and (–)-allo-normuscarone. From these were prepared by reduction with LiAlH₄ optically active stereoisomeric noralcohols. The natural stereoisomeric muscarines so far isolated are: (+)-(2S, 3R, 5S)-muscarine, (–)-(2S, 3R, 5R)-allo-muscarine and (+)-(2S, 3S, 5S)-epi-muscarine. Identical chirality appears only at C(2). This fact has to be taken into consideration for further speculations about the biogenesis of muscarines. Optically active muscarone and normuscarone exhibit a strong Cotton effect at 300 nm, which is interpreted in terms of absolute configuration by analogy to optically active substituted cyclopentanones. Optically active allo-normuscarone exhibits a very weak Cotton effect only, presumably because of predominant pseudo-rotation. The relative stability of the stereoisomeric norketones has been determined. Normuscarone (cis-2,5) is by 0,39 kcal/mol more stable than allo-normuscarone (trans-2,5).     

Synthese und Bestimmung des Chiralitätssinns von (+)-(R)-1-Azabicylo[3.3.1]nonan-2-on

Synthesis and Determination of the Chirality Sense of (+)-(R)-1-Azabicyclo[3.3.1]nonan-2-one Optically active (+)-(R)-1-azabicyclo[3.3.1]nonan-2-one ((+)- 1 ) of known absolute configuration is synthesized in the following way: Resolution of (±)-piperidin-3-ethanol ((±)- 2 ) by fractional recrystallization of its diastereoisomeric salts with (+)-3-bromocamphor-8-sulfonic acid from EtOH gave a less soluble salt that yielded(+)- 2 . The chirality sense of (+)- 2 was shown to be (R) by chemical correlation with the enantiomers of 3-oxocyclopentaneacetic acid ((±)- 8 ) of known absolute configuration. This correlation was effected by a Beckmann rearrangement of the oxime (R)-9 to the pyridone (S)- 10 followed by a direct reduction with LiAlH₄ to give the enantiomer (?)-(S)- 2 that was characterized as its benzyloxycarbonyl derivative (?)-(S)- 3 . The alcohol (+)-3 was converted via (+)- 4 into the nitrile (+)-5 which gave by hydrogenolysis and hydrolysis the (R)-configurated hydrochloride (+)- 6 which was cyclized to the bicyclic (5R)-lactam (+)- 1 in 67% yield by heating with 2 equiv. of dibutyltin(IV) oxide in toluene. The nonplanar amide function in (+)- 1 with the substituents at the N-atomarranged in a trigonal pyramid causes two rather intense Cotton effects at 242 (Δ?_max = +19.5) and 211 nm(Δ?_max = ?17.9) in the CD spectrum. If the molecules of (+)- 1 do exist mainly in the chair-twistboat conformation, the amide chromophore is pyramidally deformed in a sense defined by the absolute configuration at C(5). Therefore, the CD spectrum of the (5R)-lactam (+)- 1 can be used to test theories describing the chiroptical properties of distorted amides.     

Magnetische Kernresonanz- und «Molecular Orbital»- untersuchungen über die struktur von MEISENHEIMER-komplexen 8. Mitteilung über nucleophile aromatische Substitutionsreaktionen [1]

(1) The NMR. spectra of the stable methoxide addition complexes of 2,4-dinitro-, 2,4,6-trinitro- and 2,4-dinitro-6-cyano-anisole, and the intramolecular (spiro) reaction product of 1-(2′-hydroxyethoxy)-2,4,6-trinitrobenzene demonstrate that these products are MEISENHEIMER (σ?) complexes (addition of base in position 1).     

二[1-甲基-4-(1-甲基-4-硝基吡咯-2-酰胺基)吡咯-2-酰胺基乙基]胺的合成与表征

报道了一种对称平行的多酰胺分子——二[1-甲基-4-(1-甲基-4-硝基吡咯-2-酰胺基)吡咯-2-酰胺基乙基]胺的合成方法, 以期对DNA序列进行新的特异性识别和切割, 从而研制新型有效的工具酶或抗癌药物. 合成方法简便易行、耗时短、不需过柱分离, 每步合成都有较高产率.