Über die Synthese von 1-Aryl-und 1-Alkyl-2, 3-dimethyl-chinoxalinium-perchloraten. 2. Mitteilung. Synthese und 1H-NMR.-Spektren von 2,3-Dimethyl-1-phenyl-6-X-chinoxalinium-perchloraten

On the Synthesis of 1-Aryl- and-1-Alkyl-2, 3-dimethyl-quinoxalinium Perchlorates. 2nd Communication

1 1. Mitt.: [1].

. Synthesis and ¹ H-NMR. Spectra of 2, 3-Dimethyl-1-phenyl-6-X-quinoxlinium Perchlorates The synthesis of the title compounds ( 5 ) which have been useful as precursors for a lot of conventional and new-type dyes [2-8] has yet been limited to examples with X?H [2] [3] [11] [15] and with electron-donating [4] [12] or at best slightly electron-accepting [1] [6] substituents X and R. We now describe a method suitable even for compounds 5 with strongly electron-accepting substituents: N-monosubstituted o-phenylendiamines 4 , were condensed with 2, 3-butanedione and perchloric acid in mixed solvents containing an excess of diethyl ether. The products - mostly substituted at position 6 of the quinoxalinium ring - are chracterized by ¹H-NMR. spectra, elemental analyses and in most cases by isolation of the corresponding bases 6 . Correlations of chemical shifts with Hammett's σ_p [18] are given by equations (1)-(5).     

Isolierung,Struktur und Synthese des Metaboliten von Azapropazon-dihydrat

The renal excretion of AZAPROPAZONE-DIHYDRATE (X)

1 Handelsname: PROLIXAN®. Hersteller: Siegfried AG, Zofingen.

by humans was investigated. Following oral administration a new substance was detected in the urine besides X by TLC. Both compounds were separated by preparative layer chromatography and shown to be unchanged X and its hydroxylated metabolite VIII. The structure of VIII was established by chemical and spectroscopic methods (IR., NMR.) and confirmed by synthesis (Scheme 1).     

Synthese optisch aktiver Nickel-Komplexe mit porphinoidem Ligandsystem

Synthesis of Optically Active Porphine-type Nickel Complexes Both enantiomers of [1-methyl-8 H-HDP]nickel-perchlorate

1 For nomenclature see footnote 5 in this paper.

( 2a and 2b , respectively) have been synthesized by the following reaction sequence: (a) base induced addition of (?)-( R )-2-octanol to 1 , (b) separation of the two diastereomeric monoadducts 4a and 4b , (c) reaction with methyl magnesium iodide containing an excess of methyl iodide, (d) acid induced elimination of 2-octanol from the diadducts 6a and 6b . By a similar procedure both enantiomers of [1-butyl-8 H-HDP] nickel-perchlorate ( 3a and 3b , respectively) have been prepared. The reaction of 3a with butyl lithium yields in a kinetically controlled addition predominantly the optically active cis -1, 11-dibutyl adduct 8 and in minor quantity the meso - cis -1, 11-dibutyl adduct 9 .     

Synthesis of new derivatives of insulin sequence B1-8 with improved solubility

The synthesis of the protected octapeptide N-t-butoxycarbonyl-phenylalanyl-valylasparaginyl-glutaminyl-N^im-tritylhistidyl-leucyl-S-benzhydrylcysteinyl-glycine-hydrazide

1 L

, corresponding to the amino-terminal sequence of the insulin B-chain, is described. Up to the protected octapeptide all intermediates have greatly improved solubility properties in neutral organic solvents in comparison with other synthetic derivatives of the same sequence.     

Chemie von α-Aminonitrilen. 12. Mitteilung. Sondierungen über thermische Umwandlungen von α-Aminonitrilen

Chemistry of α-Amino Nitriles

1 11. Mitteilung: [1].

. Exploratory Experiments on Thermal Reactions of α-Amino Nitriles The paper extends a previously published report [4] on chemical properties of α-amino nitriles and of members of the C₃H₄N₂ ensemble (Scheme 1) as observed in experiments carried out under non-aqueous conditions. The reactions investigated and the observations made are summarized in some detail in the English footnotes (*) referring to Schemes 1–17 and Fig. 1.     

Azimine. VII. Herstellung durch Oxydation von Triazanen

Azimines. VII

1 Teil VI, s. [1].

. Preparation by Oxidation of Triazanes A novel method for the preparation of certain azimines 4 by oxidation of 1,2,3-trisubstituted triazanes 3 is described. Treatment of 3-aryl-triazane-1,2-diesters 3a-3c with lead tetraacetate afforded the 3-aryl-azimine-1,2-diesters 4a-4c . The precursor triazanes 3a-3c were prepared by addition of p-substituted anilines to diisopropyl diazene-1,2-dicarboxylate 1b . A comparison of the spectral properties of the azimines 4 with those of the correspondingly substituted triazanes 3 reveals the unsaturated and dipolar nature of the azimines 4 .     

Enantioselektive 1,2-Additionen von Li-, Mg-, Zn- und Cu-organischen Verbindungen und von Li-Enolaten an Carbonylverbindungen im chiralen Medium DDB

Enantioselective 1,2-addition of Li-, Mg-, Zn-, and Cu-organic compounds and of Li-enolates to carbonyl derivatives in the chiral medium DDB

1 DDB = 1,4-Dimethylamino-2,3-dimethoxybutan (= 2,3-Dimethoxy-N,N,N′,N′-tetramethyl-1,4-butandiamin).

The (+)-enantiomer of the methoxyamine DDB is used as a chiral cosolvent in the title reactions. As evident from the results listed in the table, enantiotopic faces are generally differentiated with preferences ranging from 55:45 to 60:40.     

Zur Synthese von β-Isosantalol

The synthesis of a new allylic alcohol with a norbornane skeleton is described. The convergent synthesis leads from 3-methylene-norbornan-2-one to -isosantalol (6). An important structural parameter of6 is derived from -Santalol (1), the main constituent of east indian sandalwoodoil with a powerful woody fragrance. Another structural parameter of6 is derived from isosantalol (3) with a weak woody odour. The odour of the new alcohol6 is weaker than that of3, probably because of too much osmophoric groups and a very reactivecis-1,3-butadiene-system. Another possible route to6 by means of aWittig-reaction did not succed.

Teil der Diplomarbeit vonM. Wiedenhorn, Universität Wien, 1980.     

23Na-NMR. Linewidths in Binary Mixtures of Oxygenated Solvents

The inference of single bicyclic intermediates in the competition of diglyme (or triglyme)

1 For abbreviations see the table of [1].

with tetrahydrofurfuryl alcohol is confirmed by analysis of the linewidths. The dissymetric bicyclic species are characterized by linewidths increased markedly with respect to the pure solvents, without an accompanying change in the ²³Na chemical shift. Conversely, the competition of glyme with the same alcohol involves three equi-probable intermediates; that of tetrahydrofuran (or tetrahydropyran) is of greater conceptual complexity.     

Structure et synthèse de la damascénone (triméthyl-2,6,6-trans-crotonoyl-1-cyclohexadiène-1,3), constituant odorant de l'essence de rose bulgare (rosa damascena Mill.

Damascenone

1 DORICENONE (trade mark applied for by Firmenich & Cie, Geneva).

an odoriferous ketone isolated in minute amounts from Bulgarian rose oil (Rosa damascena Mill.) is shown to be trans-2,6,6-trimethyl-1-crotonoyl-cyclohexa-1, 3-diene (I). A synthesis starting from beta;-cyclocitral is described for this conspicuous constituent of rose oil, which displays a powerful fragrance. The synthesis of four related, more saturated ketones, damascones

2 DORINONE (trade mark applied for by Firmenich & Cie, Geneva).

, is also described.     

Studien Über die Saponine aus der Arznei-Ginseng-Wurzel: Massenspektren von Ginsenoside-Rg1-Decaacetat und Verwandten Verbindungen

Mass spectra of ginsenoside-Rg1 deca-acetate

1 Siehe Lit.2.

and the related dammaran-type triterpene saponin acetates have been studied and a comment is given on the structure of panaxoside A (=ginsenoside-Rg1) proposed by Elyakov, et al .     

Enantioselektive 1,4-Additionen von metallorganischen Verbindungen an konjugierte Systeme im chiralen Medium DDB

Enantioselective 1,4-additions of organometallic compounds to conjugated systems in the chiral medium DDB

1 DDB = 1,4-Dimethylamino-2,3-dimethoxybutan (= 2,3-Dimethoxy-N,N,N′,N′-tetramethyl-1,4-butandiamin).

The chiral methoxyamine DDB is used as a cosolvent to add achiral Li-, Cu-, and Zn-organic compounds enantioselectively to prochiral β-carbon atoms of α, β-unsaturated aldehydes, ketones, nitro compounds and ketene-thioacetals (Tables 1 and 2). The selectivity generally ranges from 55:45 to 63:27, in one case ( 9b ) an enantiomeric excess of 43% was obtained.     

Dediazoniation of Arenediazonium Ions in Homogeneous Solution. Part XII. Solvent effects in competitive heterolytic and homolytic dediazoniations

In heterolytic dediazoniations arenediazonium salts form aryl cations. The reaction rates are relatively slow; they depend only to a small extent on the solvent. It is shown that the solvents in which the heterolytic dediazoniation mechanism is predominant have a low nucleophilicity, whereas in solvents of high nucleophilicity homolysis of arenediazonium salts, i.e. the formation of aryl radicals and related intermediates, is favoured. Under comparable conditions, homolytic rates are faster than the corresponding rates of heterolysis. Homolysis is strongly enhanced by addition of nucleophiles which form relatively stable radicals by electron transfer. The ability of additives to catalyze homolysis of arenediazonium salts can be explained using the concept of a nucleofugic

1 In the original proposal [32] we used the word nucleofugal. In keeping with a forthcoming proposal on nomenclature in physical organic chemistry by Commission III.2 (Physical Organic Chemistry) of IUPAC we now use the word nucleofugic.

homolytic leaving group.     

On Cardioactive Steroids. VIII. The Synthesis of Bufalin and Resibufogenin Isomers

α-Isobufalin

1 Systematic names are given at the titles of the Exper. Part.

( 1 ) and β-isoresibufogenin ( 3 ) have been synthesized from testosterone by a method which features a novel oxidative furan to pyrone transformation.     

Siliciumverbindungen mit starken intramolekularen sterischen Wechselwirkungen. 54. Versuchte Erzeugung eines Diaminosilylens: Bildung von Spirosilanen und von verwandten Verbindungen

Silicon Compounds with Strong Intramolecular Steric Interactions. 54

1 Mitteilung 53: K. Peters, E.-M. Peters, H. G. von Schnering, H. Piel, M. Weidenbruch, Z. Kristallogr., im Druck.

. Attempted Generation of a Diaminosilylene: Formation of Spirosilanes and of Related Compounds Treatment of the bulky substituted N,N′-bis(2,6-dimethylphenyl)ethylenediamine with n-butyllithium and subsequent cyclization with trichlorosilane or silicon tetrachloride gives the 2-chloro- and 2,2-dichloro-1,3-diaza-2-silacyclopentanes 3 and 4 , respectively. Both compounds can easily be converted into the azido- ( 5 ) and diazidosilanes ( 6 ) and into the trisilane 7 . Chlorine elimination from 4 in the presence of 2,3-dimethylbutadiene leads to the spirosilane 9 containing a nine-membered ring, whose structure was confirmed by X-ray crystallography. Reaction of 4 with lithium, followed by treatment with isopropanol gives beside other products the compound 10 consisting of two diazasilacyclopentane rings linked by a bridging ethylenediamino group. The X-ray structure determination of 10 shows that all six nitrogen atoms have a nearly planar environment. Upon photolysis, the azidosilane 5 provides the disiladispiro compound 12 , presumably via a silanimine intermediate.     

Ein einfacher Zugang zu 4-hydroxy-2,5-dimethyl-3(2H)-furanon (furaneol), einem Aromabestandteil von Ananas und Erdbeere

Furaneol®

1 Registered trade mark of Firmenich SA.

[4-hydroxy-2,5-dimethyl-3(2H)-furanone ( 1 )], a flavour component of pineapple and strawberry, has been prepared by a two-step synthesis starting with readily available 3-hexyne-2,5-diol. By the same method 4-hydroxy-5-methyl-3(2H)-furanone ( 2 ) and 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone ( 3a ) have been prepared from 2-pentyne-1,4-diol and 3-heptyne-2,5-diol, respectively.     

Reactions of the Carbonyl Group in Fluorinated Ketones

The chemistry of polyfluorinated ketones has recently received a great deal of attention.

1 A. Ya. Yakoubovich, Usp. Chim. 25, 3 (1956).

2 H. P. Braendlin and E. T. McBee in: Advances in Fluorine Chemistry. Butterworths, London 1963, Vol. 3, p. 1.

3 The review by Braendlin and McBee [2] does not deal only with perfluorinated ketones; moreover, though published in 1963, it is already outdated. The papers discussed in [1,2] will not be reviewed in the present article.

. The carbonyl and imino groups of the fluorinated ketones and their imines react in many different ways. In particular, the electron-attracting perfluoroalkyl groups intensify the electrophilic properties and weaken the nucleophilic properties of the carbonyl group. The perfluoroalkyl group also hinders the heterolytic removal of the hydroxyl group from adducts by reducing the stability of the carbonium ion . The increased electrophilicity of the carbonyl group and the increased stability of the addition products leads not only to a change in reactivity in the characteristic ketone reactions, but also to numerous new reactions which are not observed with non-fluorinated ketones. Thus it is possible to synthesize a wide variety of fluoroorganic compounds from perfluorinated ketones.

4 We have been concerned mainly with hexafluoroacetone, since in addition to being the most readily available and simplest perfluorinated ketone, this is also a typical representative of this class of compounds.

.     

The Conquest of Taxol

Much has been written about taxol, one of the newest weapons against cancer, and its producer, the Pacific Yew tree (Taxus brevifolia).

1 K. C. Nicolaou, W.-M. Dai, R. K. Guy, Angew. Chem. 1994, 106, 38–69; Angew. Chem. Int. Ed. Engl. 1994, 33, 15–44.

In this article, the authors give a frank and behind-the-scenes account of their encounter with this well-known molecule, which they and their collaborators faced as a synthetic target.

2 K. C. Nicolaou, Z. Yang, J.-J. Liu, H. Ueno, P. G. Nantermet, R. K. Guy, C. F. Claiborne, J. Renaud, E. A. Couladouros, K. Paulvannan, E. J. Sorensen, Nature (London) 1994, 367, 630–634.

3 K. C. Nicolaou, J.-J. Liu, Z. Yang, H. Ueno, R. K. Guy, E. A. Couladouros, E. J. Sorensen, J. Am. Chem. Soc. 1995, 117, 624–633.

4 K. C. Nicolaou, J.-J. Liu, Z. Yang, H. Ueno, E. J. Sorensen, C. F. Claiborne, R. K. Guy, C.-K. Hwang, M. Nakada, P. G. Nantermet, J. Am. Chem. Soc. 1995, 117, 634–644.

5 K. C. Nicolaou, Z. Yang, J.-J. Liu, P. G. Nantermet, C. F. Claiborne, J. Renaud, R. K. Guy, K. Shibayama, J. Am. Chem. Soc. 1995, 117, 645–652.

6 K. C. Nicolaou, H. Ueno, J.-J. Liu, P. G. Nantermet, Z. Yang, J. Renaud, K. Paulvannan, R. Chadha, J. Am. Chem. Soc. 1995, 117, 653–659.

Once again total synthesis is found to offer excellent opportunities for developing new synthetic strategies and novel reactions. The team of chemists who took up this challenge emerged with valuable experience and confidence in their skills.     

The He(Iα) Photoelectron Spectra of the Perfluoroderivatives of Trisannelated Benzenes and Tetrakisannelated Cyclooctatetraenes

The He(Iα) photoelectron (PE) spectra of tris(perfluorocyclobuta)benzene 4 (F)

1 3,3,4,4,7,7,8,8,11,11,12,12-Dodecafluorotetracyclo[8.2.0.0^2,5.0^6,9]dodeca-1,5,9-triene

, tris(perfluorocyclopenta)benzene 5 (F)

2 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9-Octadecafluoro-2,3,4,5,6,7,8,9-octahydro-1H-trindene.

, tetrakis(perfluorocyclobuta)cyclooctatetraene 6 (F)

3 3,3,4,4,7,7,8,8,11,1l,l2,l2,l5,15,16,16-Hexadecafluoropentacyclo[12.2.0.0^2,5.0^6,9.0^10,13]hexadeca-1,5,9,13-tetraene.

, and of tetrakis(perfluorocyclopenta)cyclooctatetraene 7 (F)

4 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12-Tetracosafluoro-1,2,3,4,5,6,7,8,9,10,11,12-dodeca-hydrotetracyclopenta[a,c,e,g]cyclooctene.

are reported. A tentative assignment of the PE spectra is derived by empirical correlation with those of relevant reference compounds. The results suggest that 6 (F) retains the D_4h-conformation in the gas phase, i.e. A conformation with a planar cyclooctatetraene ring, as observed in the crystal. All four compounds exhibit a sharp increase of their first ionization energies, relative to the corresponding parent hydrocarbons, due to the perfluoro effect.     

Etude dans la série des radicaux hétérocycliques. Partie XV. Décomposition aprotique de l'amino-6-éthyl-2-benzothiazole dans des substrats aromatiques et hétéroaromatiques: préparation des mésityl-6- et furyl-6-éthyl-2-benzothiazoles,des sels quaternaires et des spiropyrannes correspondants

Study of heteroaromatic radicals. Part XV .

1 Partie XIV: cf. [1].

Aprotic decomposition of 6-amino-2-ethylbenzothiazole in aromatic and heteroaromatic substrates: preparation of 6-mesityl- and 6-furyl-2-ethylbenzothiazoles and of the corresponding quaternary salts and spyropyrans In the presence of excess isopentyl nitrite in aprotic solvent, the 6-amino-2-ethyl-benzothiazole leads to 6-aryl- and 6-heteroaryl-2-ethylbenzothiazoles 1 to 14 in ca. 20–50% yield (Scheme 1, Table 1). The 2-ethyl-6-benzothiazolyl radicals generated during these reactions exhibit a weak electrophilic character (Table 2). Preparatively this method has been applied to the synthesis of 6-mesityl- and 6-furyl-2-ethylbenzothiazoles 6 and 7 , which were used to prepare the corresponding quaternary salts 15 , 16 and the spiropyrans 19, 20 (Scheme 4).