Alkylierung in der 2-Stellung von (2S, 4R)- 4-Hydroxyprolin unter Retention

Alkylation in the 2-Position of (2S, 4R)-4-Hydroxyproline with Retention of Configuration O-Acetyl-4-hydroxyproline ( 1b ) is condensed with pivalaldehyde to give a single stereoisomer of the 2-(tert-butyl)-4-oxo-3-oxa-1-azabicyclo[3.3.0]oct-7-yl acetate ( 3 ). This is converted to the enolates 4 or 5 , reactions of which with alkyl halides, aldehydes, and acetone (→ 6,9,10,11 ) are diastereoselective (lk-1,3-induction). Cleavage of the corresponding products furnishes the enantiomerically pure 2-deuterio-, 2-methyl-, 2-allyl-, and 2-benzyl-substituted 4-hydroxyprolines 2a–2d .     

Synthese von in 2- bzw. 3-Stellung substituierten Alkandiphosphonsäuren

Synthesis of 2- or 3-substituted Alkanediphosphonic Acids Syntheses of substances of the general formula RCX(PO₃H₂)₂ X = OH, H, Cl, NH₂ have been known for a long time. The preparative possibilities for the synthesis of alkanediphosphonic acids containing an amino group or a chlorine atom in the 2- or 3-position were limited, only 2 substances from this class of compounds being known. Further examples of this class of substances have been synthesized.     

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 .     

Synthese von phenoxygruppenhaltigen Derivaten der Methandiphosphonsäure

Synthesis of Phenoxy Derivatives of Methanediphosphonic Acid Derivatives of the methanediphosphonic acid containing different numbers of phenoxy groups were prepared by Michaelis-Arbusov reaction of iodomethane phosphonic acid esters with phosphorous acid esters and by reaction of methane diphosphonic acid tetrachlorid with sodium phenolate. The obtained products were investigated by means of n.m.r. spectroscopy.     

Oxydation von nichtcyclischen Derivaten der Methylarsonigsäure

Oxidation of Noncyclic Derivatives of Methylarsonous Acid Reaction of methyldichloroarsine with alcohols and sec. amides yields esters, diamides and amidechlorides of methylarsonous acid. Oxidation with o-chloranil yields the corresponding derivatives of methylarsonic acid.     

Synthese und Kristallstruktur der Hydroxy-lactone von 6-Methyl-2-propionyl- und 3-Methyl-2-propionylbenzoesäure

The isomers 6-methyl-2-propionyl- and 3-methyl-2-propionylbenzoic acid were synthesized and separated by DCC (droplet counter-current) chromatography. The crystal structure analyses showed that these compounds are hydroxylactones in the solid state.     

Notiz über die Bestimmung der absoluten Konfiguration von (+)-2-Hydroxy-2, 3-dimethylbuttersäure

Note on the Determination of the Absolute Configuration of (+)-2-Hydroxy-2, 3-dimethylbutyric Acid Chemical correlation of the title compound 1 with (S)-3-isopropyl-3-methyl-5-trimethylsilyl-4-penten-2-one ( 2 ) showed (+)- 1 to have (S)-configuration. Key step was the Baeyer-Villiger oxidation of a very hindered, optically active methyl keton to the corresponding acetoxy compound with trifluoroperacetic acid using slightly modified buffer conditions. It is found, that the erythro/threo assignment of an α, α-disubstituted β-hydroxyester intermediate can be based on the observation, that the ¹H-NMR. signal of H? C(β) of the erythro isomer appears at lower field than that of the threo isomer.     

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.     

Katalyse der Reaktion von Thionylchlorid mit Trichloressigsäure

The reaction of thionyl chloride with trichloroacetic acid is catalyzed by tetraethylammonium chloride, and the rate is proportional to the concentration of the salt. The catalytic activities of tetraethylammonium chloride, pyridine hydrochloride and piperidine hydrochloride are in the ratio 1: 0.4: 0.3.     

Die Koordinationszahl von Lanthaniden: Thermodynamik der LnIIIEDTA-Mischkomplexe mit den Anionen der 8-Hydroxychinolin-5-sulfonsäure,Iminodiessigsäure und Nitrilotriessigsäure

The values of ΔG, ΔH and ΔS for the formation of the mixed 1:1:1 lanthanide EDTA complexes with the anions of 8-hydroxyquinoline-5-sulfonic acid, iminodiacetic acid and nitrilotriacetic acid were determined by pH-titrations and a direct calorimetric method. These thermodynamic data are discussed and compared with those for the formation of the Ln(III)EDTA complexes. Contrary to current opinion it is concluded that all trivalent lanthanide aquoions have the same coordination number in dilute solution. However, in the series of the lanthanide EDTA complexes the coordination number changes between Sm and Tb. In this region, equilibria occur between two types of EDTA complexes with different numbers of coordinated water molecules: The corresponding equilibrium constants could be evaluated. The coordination number changes also in many other Ln complexes along the lanthanide series, and similar equilibria occur.     

Stereoselektive Alkylierung an C(α) von Serin,Glycerinsäure,Threonin und Weinsäure über heterocyclische Enolate mit exocyclischer Doppelbindung

Steroselective Alkylation at C(α) of Serine, Clyceric Acid, Threonine, and Tartaric Acid Involving Heterocyclic Enolates with Evocyelic Double Bonds The chiral, non-racemic title acids are converted to methyl dioxolane-(cf. 13 ), oxazoline-( 4 ) and oxazolidinecarboxylates (cf. 9 ). Deprotonation by Li(i-Pr) ₂N at dry-ice temperature gives solutions of the lithium enolates A–D With exocyclic enolate double bonds. These are stable crough with respect to β-elimination (Scheme 1) to be alkylated with or without cosolvents such as HMPA or DMPU The products are formed in good to excellent yields and, with the exception of the tartrate-derived acetonlde (see Scheme 2), with diastereoselectivities above 90%. While the tartrate-and threonine-derived enolates ( A and B , resp.) are chiral due to the second stereogenic center of the precursors, the serine- and glyceric-acid-derived enolates ( A and B , resp.) are chiral due to the second sterogenic center of the precursors, the serine-nd glyceric-acid-derived enolates are non-racemic due to a tert butyl-substituted (pivalaldehyde-derived) acetal center ( C and D , resp.). The products of alkylation can be hydrolyzed to give α-branched tartaric acid (Scheme 2), allothreonine (Scheme 3), serine (Scheme 4), and glyceric-acid derivatives (Scheme 5) with quaternary stereogenic centers. The configurations of the products are determined by NOE-NMR measurements and by chemical correlation. These show that the dioxolane-derived enolates A and D are alkylated preferentially from that face of the ring which is already substituted (‘syn’-attack), while the dihydrooxazol-and oxazolidine-derived enolates B and C are alkylated from the opposite face (‘anti’-attack). The ‘syn’-attack is postulated to arise from strong folding of the heterocyclic ring due to electronic repulsion between the enolate π-system and non-bonding electron pairs on the heteroatoms (see Scheme 6).