Stoffwechselprodukte von Mikroorganismen. 101. Mitteilung. Synthese der trans-5-Hydroxy-3-methylpenten-(2)-säure (trans-Δ2-Anhydromevalonsäure)

trans-Δ²-Anhydromevalonic acid (XVII) was prepared by a Wittig reaction, starting from (4-tetrahydro-2-pyranyloxy)-2-butanone. On the other hand, the corresponding 4-acetoxy-2-butanone gave, under similar conditions, the cyclohexene derivative V, explainable by a twofold Michael addition of the Wittig reagent to methyl vinyl ketone, followed by an intramolecular alcol condensation.     

NMR.-spektroskopische Methoden als Reinheitskriterien isomerer Weinsäuren und Weinsäureester

NMR.-spectroscopic Methods as Criteria of the Purity of Isomeric Tartaric Acids and Their Esters meso-Tartaric acid ( 2 ) can be distinguished either from the natural (+)-(2R, 3R)-tartaric acid ( 1 ) or the ‘unnatural’ (?)-(2S, 3S)-tartaric acid ( 1 ′) or their racemic mixture, by ¹H-NMR.-spectral resolution using europium chloride in aqueous solution. Diastereomeric esters have been prepared from different esters of tartaric acid 3 and the Mosher reagent 4 and the purities of the enantiomers of 3 have been checked by ¹H-NMR. spectroscopy.     

Bemerkungen zur Synthese von 5-Amino-m-xylol-2-sulfonsäure und 5-Amino-m-xylol-4-sulfonsäure

Some comments on the syntheses of 5-amino-m-xylene-2-sulfonic acid and 5-amino-m-xylene-4-sulfonic acid Treatment of 5-amino-m-xylene ( 1 ) with oleum led to a 55:45 mixture of 5-amino-m-xylene-2-sulfonic acid ( 2 ) and 5-amino-m-xylene-4-sulfonic acid ( 3 ). The structure of both isomers was proven by reaction of sulfur dioxide with the diazonium chlorides derived from 2-amino-5-nitro-m-xylene ( 5 ) and 4-amino-5-nitro-m-xylene ( 8 ) giving 5-nitro-m-xylene-2-sulfonyl chloride ( 6 ) and 5-nitro-m-xylene-4-sulfonyl chloride ( 9 ) respectively, followed by hydrolyses to the corresponding sulfonic acids 7 and 10 , and final Béchamp reductions. The sulfonic acid 2 was also prepared by sulfonation of 5-acetylamino-m-xylene ( 4 ) to 5-acetylamino-m-xylene-2-sulfonic acid ( 11 ) and subsequent hydrolysis. A further procedure for the synthesis of 3 was sulfonation of 5-amino-2-chloro-m-xylene ( 12 ) – prepared by Béchamp reduction of 2-chloro-5-nitro-m-xylene ( 13 ) – or of 5-amino-2-bromo-m-xylene ( 15 ) – prepared by bromination of 4 and subsequent hydrolysis – to 5-amino-2-chloro-m-xylene-4-sulfonic acid ( 16 ) and 5-amino-2-bromo-m-xylene-4-sulfonic acid ( 17 ) respectively, followed by hydrogenolysis.     

Bemerkungen zur Synthese von 3-Aminotoluol-5-sulfonsäure und 2-Aminotoluol-3-sulfonsäure

Some comments on the synthesis of 3-aminotoluene-5-sulfonic acid and 2-aminotoluene-3-sulfonic acid. Sulfonation of 3-nitrotoluene ( 5 ) yields predominantly the unsymetrical isomer 5-nitrotoluene-2-sulfonic acid ( 7 ), and lesser amounts of 5-nitrotoluene-3-sulfonic acid ( 6 ), previously reported as the major product. The desired 5-aminotoluene-3-sulfonic acid ( 3 ) was synthesized in preparative amounts from 6-aminotoluene-3-sulfonic acid (4) via the following sequence of reactions: diazotation and Sandmeyer replacement of 6-chlorotoluene-3-sulfonic acid ( 13 ), nitration of the sulfonyl chloride 14 under suitable conditions to give isomer free 6-chloro-5-nitrotoluene-3-sulfonyl chloride ( 15 ), hydrolysis to the sulfonic acid 16 and finally, simultaneous hydrogenolysis and reduction to 3 . The isomeric 7 was unequivocally prepared from 2-amino-5-nitrotoluene ( 9 ) via two routes: (1) diazotation, Sandmeyer thiocyanatation to 5-nitro-2-thiocyanatotoluene ( 10 ), Na₂S reduction to the di(2-methyl-4-nitro-phenyl)-disulfide ( 11 ), treatment with nitric acid and chlorine to give 5-nitrotoluene-2-sulfonyl chloride ( 12 ) and finally alkaline hydrolysis to 7 ; (2) Meerwein's SO₂ treatment of the diazonium salt derived from 9 leads directly to 12 and thence to 7 . 2-Aminotoluene-3-sulfonic acid ( 1 ) was prepared from the key intermediate 3-amino-2-nitrotoluene ( 18 ) via the same two routes used to prepare 7 from 9 . Both reaction sequences provided 2-nitrotoluene-3-sulfonly chloride, the hydrolysis product of which was reduced to 1 . Intermediate 18 was prepared in the following four steps from m-toluic acid ( 19 ): nitration to the 2-nitroderivative ( 20 ), whose acid chloride ( 21 ) was converted to 2-nitro-m-toluamide ( 22 ), and Hoffmann rearrangement to 18 .     

Über Chalkogenolate. 89. Untersuchungen über N-Dicyandithiocarbamidsäure Darstellung und Eigenschaften der freien Säure

On Chalcogenolates. 89. Studies on N-Dicyandithiocarbamic Acid. Preparation and Properties of the Free Acid Colorless N-dicyandithiocarbamic acid (melting point: 112°C) has been prepared by reaction between a suspension of K[S₂C? N(CN)₂] in diethyl ether and a solution of HCl in (C₂H₅)₂O at 0°C; the ether was distilled off at 0°C in vacuo. The compound has been characterized by means of infared spectra, electron absorption spectra, ¹H-NMR spectra, and mass spectra. The dissociation constant of N-dicyandithiocarbamic acid in water is K_a = (1.69 ± 0.1) X 10^?1 20°C. The thermodynamic data of the dissociation were calculated.     

Nickelphosphankomplexe der Mercaptoessigsäure

Nickel Complexes of Mercaptoacetic Acid The reaction of [Cp°₂Zr(OOCCH₂SH‐κ¹O)(OOCCH₂SH‐κ²O, O′)] (Cp° = C₅EtMe₄) with [NiCl₂(PMe₂Ph)₂] or [NiCl₂(dppe)] (dppe = PPh₂CH₂CH₂PPh₂) in the presence of NEt₃ yields the tetranuclear Zr^IV/Ni^II complex [{Cp°₂Zr(κ¹O‐OOCCH₂S‐κ²O′, S)(κ²O, O′‐OOCCH₂S‐κ¹S)Ni(PMe₂Ph)}₂] ( 1 ) and the chelate complexes [Ni(OOCCH₂S‐κ²O, S)L₂] [L = PMe₂Ph ( 2 ), L₂ = dppe ( 3 )]. 2 and 3 are also accessible from [NiCl₂(PMe₂Ph)₂] or [NiCl₂(dppe)] and mercaptoacetic acid in the presence of NEt₃ in quantitative yield. The structure of 2 is dynamic in solution, whereby a complex with three‐coordinate nickel atom is formed. 2 and 3 were characterized spectroscopically (¹H, ¹³C, ³¹P NMR and IR) and by crystal structure determination.     

Über Chalkogenolate. 81. Untersuchungen über N-Hydroxydithiocarbamidsäure 3. Ester der N-Hydroxydithiocarbimidsäure und -carbamidsäure

On Chalcogenolates. 81. Studies on N-Hydroxy Dithiocarbamic Acid. 3- Esters of N-Hydroxy Dithiocarbimic Acid and Dithiocarbamic Acid The reaction between hydroxylamine, carbon disulfide, and alkyl halide leads to the corresponding ester of N-hydroxy dithiocarbimic acid HO? N?C(SR)₂ with R = CH₃, C₂H₅; R₂ = ? CH₂? CH₂? . The phenyl ester of N-hydroxy dithiocarbamic acid HO? NH? CS(SC₆H₅) has been prepared by reaction of hydroxylammonium chloride with the phenyl ester of chlorodithioformic acid. N-Methyl hydroxylammonium chloride reacts with carbon disulfide and alkyl iodide to form the corresponding ester of the dithiocarbamic acid HO? N(CH₃)? CS(SR) with R = CH₃, C₂H₅. The unstable compounds have been characterized by different methods.     

Beiträge zur Chemie des Phosphors. 87. 1,2-Di-tert-butyl-3-iso-propyl-cyclotriphosphan,ein stabiles gemischt-substituiertes Cyclotriphosphan

Contributions to the Chemistry of Phosphorus. 87. 1,2-Di-tert-butyl-3-iso-propyl-cylclotriphosphane, a Stable Mixed-substituted Cyclotriphosphane The first kinetically stable mixed-substituted cyclotriphosphane, 1,2-di-tert-butyl-3-iso-propyl-cyclotriphosphane, (PBu^t)₂(PPrⁱ) ( 1 ), was synthesized by [2+1]-cyclocondensation of K(Bu^t)P–P(Bu^t)K with PrⁱPCl₂ in n-pentane. Mainly (PBu^t)₄ as well as mixed-substituted cyclotetra- and cyclopentaphosphanes are formed as by-products. 1 could be isolated in a pure state by high vacuum distillation and was thoroughly characterized. It forms two diastereomers, the more stable of which with a cis-standing tert-butyl and iso-propyl group can be stored without decomposition under inert conditions at room temperature for several days. Through thermolysis of 1 beside other alkylcyclophosphanes the mixed-substituted cyclotetraphosphanes (PBu^t)₂(PPrⁱ)₂ ( 2 ) and (PBu^t)₃(PPrⁱ) ( 3 ) are formed and their ³¹P NMR parameters are reported.     

Über Chalkogenolate. 93. Untersuchungen über Trithioallophansäure 2. Darstellung und Eigenschaften der freien Säure [1]

On Chalcogenolates. 93. Studies on Trithioallophanic Acid 2. Preparation and Properties of the Free Acid Yellow trithioallophanic acid H₂N? CS? NH? CS(SH) has been prepared by reaction between a suspension of K[S₂C? NH? CS? NH₂] in diethyl ether and a solution of HCl in (C₂H₅)₂O at ?15°C; the ether was distilled off at ?15°C in vacuo. The compound has been characterized by means of infrared spectra, electron absorption, ¹H-NMR spectra, and mass spectra. The dissociation constant of trithioallophanic acid in water is K_a = (1,41 ± 0,08) · 10^?2 at 20°C.     

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.     

Herstellung enantiomerenreiner Derivate von 3-Amino- und 3-Mercaptobuttersäure durch SN2-Ringöffnung des β-Lactons und eines 1,3-Dixoanons aus der 3-Hydroxybuttersä ure

Preparation of Enantiomerically Pure Derivatives of 3-Amino- and 3-Mercaptobutanoic Acid by S_N2 Ring Opening of the β-Lactone and a 1,3-Dioxanone Derived from 3-Hydroxybutanoic Acid From (S)-4-methyloxetan-2-one ( 1 ), the β-butyrolactone readily available from the biopolymer ( R )-polyhydroxybutyrate (PHB) and various C, N, O and S nucleophiles, the following compounds are prepared:(s)-2-hydroxy-4-octanone ( 3 ), (R)-3-aminobutanoic acid ( 7 ) and its N-benzyl derivative 5 , (R)-3-azidobutanoic acid ( 6 ) (R)-3-mercaptobutanoic acid ( 10 ), (R)-3-(phenylthio)butanoic acid ( 8 ) and its sulfoxide 9 . The (6R)-2,6-dimethyl-2-ethoxy-1,3-dioxan-4-one ( 4 ) from (R)-3-hydroxybutanoic acid undergoes S^N2 ring opening with benzylamine to give the N-benzyl derivative (ent- 5 ) of (S)-3-aminobutanoic acid in 30?40% yield.     

Über Chalkogenolate. LVIII. Untersuchungen über Thiomeiensäuren 6. Cyandithioameisensäure und Azidodithioameisensäure

Polymeric cyanodithioformic acid has been prepared by interaction between a solution of Na[NCCS₂]. 3 DMF and HCl(aq). In the gaseous state there exists [NCCS(SH)]_x with x = 1 and 2. The instable crystalline acidodithioformic acid is formed on reaction of Na[N₃CS₂] with HCl(aq). In the gaseous state there exists the monomeric acid N₃CS(SH).     

Der geschwindigkeitsbestimmende Schritt bei der Decarboxy-lierung von 2,4-Dihydroxybenzoesäure in mässig konzentrierter wässeriger Salzsäure

The decarboxylation kinetics of 2,4-dihydroxybenzoic acid have been studied in 0.1–8 N aqueous HCl at 50°. At low HCl concentrations, the observed first order rate constant, k, increases with increasing acidity of the solution. In solutions with 3.5–6 N HCl, k remains constant. The D₂O solvent isotope effect decreases from ^kH₂O/^kD₂O = 2.0 in 1N HCl to 1.3 in 5 N HCl, and it remains unchanged at 1.3 if the HCl concentration is increased further to 8 N. It is concluded that an increase of the acidity of the solution causes a change of the rate determining step from slow proton transfer to rate limiting C? C bond cleavage.     

Preparation of densely grafted poly(aniline‐2‐sulfonic acid‐co‐aniline)s as novel water‐soluble conducting copolymers

Various densely grafted polymers containing poly(aniline‐2‐sulfonic acid‐co‐aniline)s as side chains and polystyrene as the backbone were prepared. A styryl‐substituted aniline macromonomer, 4‐(4‐vinylbenzoxyl)(N‐tert‐butoxycarbonyl)phenylamine (4‐VBPA‐^tBOC), was first prepared by the reaction of 4‐aminophenol with the amino‐protecting moiety di‐tert‐butoxyldicarbonate, and this was followed by substitution with 4‐vinylbenzyl chloride. 4‐VBPA‐^tBOC thus obtained was homopolymerized with azobisisobutyronitrile as an initiator, and this was followed by deprotection with trifluoroacetic acid to generate poly[4‐(4‐vinylbenzoxyl)phenylamine] (PVBPA) with pendent amine moieties. Second, the copolymerization of aniline‐2‐sulfonic acid and aniline was carried out in the presence of PVBPA to generate densely grafted poly(aniline‐2‐sulfonic acid‐co‐aniline). Through the variation of the molar feed ratio of aniline‐2‐sulfonic acid to aniline, various densely grafted copolymers were generated with different aniline‐2‐sulfonic acid/aniline composition ratios along the side chains. The copolymers prepared with molar feed ratios greater than 1/2 were water‐soluble and had conductivities comparable to those of the linear copolymers. Furthermore, these copolymers could self‐dope in water through intermolecular or intramolecular interactions between the sulfonic acid moieties and imine nitrogens, and this generated large aggregates. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1090–1099, 2005     

Über Chalkogenolate. 136 [1]. Alkylester der Cyanoameisensäure und der Cyanomonothioameisensäure

On Chalcogenolates. 136. Alkyl Esters of Cyanoformic Acid and of Cyanomonothioformic Acid By use of the phase transfer catalyst 18-crown-6 the esters CH₃O—CO—CN, C₂H₅O—CO—CN, C₂H₅S—CO—CN, and ⁿC₃H₇S—CO—CN have been prepared by reaction of the corresponding chloro compound with potassium cyanide. The prepared compounds have been characterized by means of electron absorption, infrared, nuclear magnetic resonance (¹H and ¹³C), and mass spectra.     

Über die Reaktion von Propiolsäure und Propiolsäureester mit Cyclohexanon

In the presence of potassium t-butoxide or potassium hydroxide, propiolic acid adds two molecules of cyclohexanone to form the isomeric seq-cis- and seq-trans-7, 14-Dioxa-dispiro[5.1.5.2]pentadec-15-yliden-acetic acids IIa and IIIa, respectively. Methyl propiolate and cyclohexanone react analogously in the presence of potassium t-butoxide, yielding the corresponding esters. The structure of these condensation products follows from their physical properties and from degradation reactions to known compounds.     

Zur Stabilität der Metallkomplexe von Methantriessigsäure und cis,cis-1,3,5-Cyclohexantricarbonsäure

The stabilities of the Mn²⁺-, Co²⁺-, Ni²⁺-, Cu²⁺- and Zn²⁺-complexes with 2-(carboxymethyl)glutaric acid ( 2 ) and cis,cis-1,3,5-cyclohexanetricarboxylic acid ( 3 ) were measured potentiometrically at 25° and I = 0.5 (KNO₃). Beside the complexes ML^? protonated species MLH and MLH are also formed. Their stability constants are given in Table 1. A comparison between the stabilities of 2 or 3 and those of acetate, as a model for a monocarboxylate, or succinate and glutarate, as examples for dicarboxylates, indicates that in all species only one carboxylate is strongly bound whereas the second and third ones are probably not. The observation that Δlog K₁ = log K ? log K as well as Δlog K₂ = log K ? log K are practically constants with values of 0.34 ± 0.05 and 0.49 ± 0.07, respectively, for both ligands and the five metal ions studied is also in line with the proposed monodentate structures of the complexes ML^?, MLH and MLH.     

Über Pterinchemie. 69 Mitteilung [1]. Konformationsanalyse von 5,6,7,8-Tetrahydropteroinsäure und 5,6,7,8-Tetrahydro-L-folsäure

Conformational analysis of 5,6,7,8-tetrahydropteroic acid and 5,6,7,8-tetrahydro-L -folic acid In the 360-MHz-¹H-NMR.-spectrum of (6R, S)-9,9-dideuterio-5, 6, 7, 8-tetrahydropteroic acid (racemic) (XIII) (AMX-System, Fig. 4) and (6R, S)-9,9-dideuterio-5, 6, 7, 8-tetrahydro-L -folic acid (diastereomeric) (XVI) the H_a–C(6) and H_a–C(7) show a vicinal coupling constant of 6,7 Hz and the H_a–C(6) and H_e–C(7) one of 3,2 Hz. The first coupling constant provides evidence for an approximate trans-diaxal arrangement of H_a–C(6) and H_a–C(7), and the second for a gauche conformation of H_a–C(6) and H_e–C(7). The tetrahydropyrazine ring in the racemic 5, 6, 7, 8-tetrahydropteroic acid (III) and in the diastereomeric 5, 6, 7, 8-tetrahydro-L -folic acid (XVII) exists therefore in a half-chair conformation with a pseudoequatorial position of the side chain at C(6) (Fig.5).     

Abkömmlinge der 3-Chinolincarbonsäure mit Sauerstoffsubstitution in Stellung 4, 5 and 8: Synthese,Reaktionen, NMR.-Studien

Derivatives of 3-Quinolinecarboxylic Acid with Oxygen Substitution in Positions 4, 5 and 8: Synthesis, Reactions, NMR. Studies Starting from either 1, 4-dibenzyloxybenzene (7) or 2, 5-dimethoxyaniline ( 16 ), synthetic routes have been developed to benzenoid and quinoid derivatives of 4-oxo-1, 4-dihydro-3-quinolinecarboxylic acid with O-bearing substituents in the positions 5 and 8 (compounds 12 - 15 , 19 , 20 , 23 , and 24 ). With the 1-ethyl-4, 5, 8 trioxo acid 14 as a dienophile, a series of linear tricyclic diene adducts ( 29 - 32 ) has been prepared, the structures of which were further modified by aromatization, reduction or dehydrogenation (compounds 33 - 40 ). A series of benzenoid and quinoid compounds with an additional substituent in position 6 or 7 (Table 1) has been derived mainly from the quinone 14 , primarily by addition of nucleophiles and eventually subsequent steps, and by aromatic electrophilic substitution of the 1-ethyl-5, 8-dimethoxy acid 23 . The substitution pattern of some of these compounds has been elucidated by detailed ¹³C-NMR. studies (Table 2) and/or nuclear Overhauser-effect studies (Table 3). Correlations, based essentially on chemical arguments, allowed to define the structures of most of the residual new compounds (Table 4).     

Über die absolute Konfiguration der Cantharsäure und des Palasonins

The absolute configurations of (+)-cantharic acid, a chiral derivative of the achiral insect defensive substance cantharidin ( 1 ), and of palasonin, a lower homologue of 1 occurring in the plant Butea frondosa, were shown to be represented by formulas 2 and 3 , respectively (scheme 1). These results were obtained by application of the Horeau method (table 1) on the (+)-cantharic acid derivatives (+)- 5 , (?)- 7 , and (?) 11 (scheme 2), and the palasonin derivatives (+)- 29 and (+)- 30 (scheme 4), as well as by comparison of the chiroptical properties (tables 2 and 3) of a number of derivatives, prepared from either cantharic acid or palasonin. – Attempts to incorporate various radioactively labelled precursors into palasonin ( 3 ), using young and adult plants, have been so far unsuccessful.