Zum Verhalten von Orthocarbonsäureestern gegenüber Trimethylsilylchlorid, -azid und -cyanid

The reaction of cyclic orthoesters of cyclohexanes and steroides with trimethylsilylchloride,-azide and-cyanide points out novel, mechanistic aspects as well as remarkable preparative possibilities. The mixture1 a/1 b of theexo/endo stereoisomers of the cyclic orthoesters derived fromcis-cyclohexane-1,2-diol was transformed to the expected 1-yl-ethanoate3 of thetrans-2-chlorocyclohexan-1-ol. In contrast the reaction of1 a/1 b with trimethylsilylazide and trimethylsilycyanide yields the correspondingexo/endo mixtures of2 a/2 b and2 c/2 d resp. The cyclic orthoester oftrans-cyclohexan-1,2-diol (4) similarily affords the products5 a and5 b, whereas transformation with trimethylsilylchloride 1-yl-ethanoate of thecis-2-chlorocyclohexan-1-ol could not be achieved for steric reasons. The cyclic orthoesters6 a/6 b ofcis-cyclohex-1-en-3,4-diol are converted regio- and stereospecifically to the products7 and9 using trimethylsilychloride and- azide, whereas theexo/endo mixture8 a/8 b of the corresponding cyclic orthoester derivative is formed with trimethylsilylcyanide. The orthoesters10 a/10 b prepared from 2,3-cis-dihydroxycyclohexanone-1 give thetrans-2-chloro-3-oxocyclohexyl-ethanoate (11) and its elimination product12. In analogy13 is produced by treating10 a/10 b with trimethylsilylacetate. Theexo/endo mixture of cyclic esters14 a/14 b 3-cholestan-2,3-diol gives the corresponding mixture15 a/15 b when treated with trimethylsilycyanide. Reaction of Trimethylsilychloride with14 a/14 b affords mainly thetrans-diequatorial product17 a and only small amounts of thetrans-diaxial product17b. In contrast the mixture18a/18b yields exclusively thetrans-diaxials product20 on reaction with trimethylsilylchloride. With trimethylsilcyanide the cyclic orthoester derivative21 a/21 b is formed. The cyclic esters22 a/22 b of 1,2-dihydroxychloestanone-3 react with trimethylsilylchloride to give the easily explicable elimination product23 and the rearranged 3-methoxy-cholesten-3-one-2 (24). The corresponding cyclic orthesters25 a/25 b of 1,2-dihydroxy-3-oxo-androstans-17-yl-ethanoate in a similar way afford the elimination product26 to a small extent and the rearranged 3-methoxy-2-oxo-androstan-17-yl-ethanoate (27) as the main product.

Herrn Prof. Dr.H. Pommer mit den besten Wünschen zum 60. Geburtstag gewidmet.     

Cycloproparenes: Approaches to cyclopropa[c]furan

Treatment of 6,6-dichloro-3-oxabicyclo[3.1.0]-hexane (7) with potassiumt-butoxide generates the ring-strained cyclopropene8 as a reactive intermediate. With 1,3-diphenylisobenzofuran compound8 is trapped as a 51 mixture of theexo- andendo-adducts11a and11b, respectively. With furan only the ring expanded vinylcarbene12 is intercepted and spirocycle13a is formed. Carbene12 is also captured by cyclohexene, 2,3-dihydrofuran, 2,5-dihydrofuran, and diphenylethyne to give22–25 respectively. A likely side product in these reactions is the pyran14.On leave from Petrolite Corporation, St. Louis, MO, USA.Taken in part from a lecture delivered at the International Chemical Congress of Pacific Basin Chemical Societies, Honolulu, December 1989 (Pacifichem '89); Abstract ORGN 016. A preliminary report was communicated (see ref. [13]).     

Über die Darstellung der 7R-Oxirane von 5Z- und 5E-10-Oxo-19-norcholecalciferol

Summary The two title compounds12b and13b have been prepared by direct oxidation of the corresponding 10-oxo-19-norcolcalciferol derivatives3c and4c withMCPBA. The generation of12b and13b by treatment of the ⁷ epoxidized ethylisoxazolin adducts of 5Z- and 5E-cholecalciferol8a,8b and9a,9b with Mo(CO)₆ failed, since besides the retroaldol cleavage of the heterocycle a deoxygenation of the oxirane with retention of configuration to the ⁷ double bond occurs.

     

δ-Santalolanaloga II Synthesen in der Isocamphanreihe, 28. Mitt.

The synthesis of 3-(3,3-dimethyl-2-exo-norbornyl)-2-methylprop-2-en-1-ol (3) and of 8-hydroxymethyl-8-methylcamphene (4) is described.3 and4 are analogues of -Santalol (1) with the allylic hydroxyl group in a position of two or three carbon atoms closer to the bicyclic nucleus compared to1. 4 is also an analogue to Patchenol® which is used sometimes to blend the patchouli oil. The odour impression of these compounds, of the pureendo-epimer of3, and of theendo-exo-mixture of3 are described and compared with the odour of1 and a further analogue whose synthesis has already been reported in a preceding paper [1].

Auszugsweise vorgetragen auf der gemeinsamen wissenschaftlichen Tagung der ÖPhG und DPhG am 11. September 1986 in Innsbruck. Die Synthese von4 wurde bereits am 15. März 1983 anläßlich des 9th International Congress of Essential Oils in Singapore vorgestellt.     

The reaction of 4-methoxycoumarins with prenyl bromide: Synthesis of 4′,4′,5′-trimethyl-dihydrofurano-coumarins and 2,2-dimethyl-chromenopyrans

The reaction of 7-hydroxy-4-methoxy- (1a), 7-hydroxy-4,5-dimethoxy-(1b) and 5-hydroxy-4,7-dimethoxy (1c) -2H-1-benzopyran-2-ones with prenyl bromide in acetone in the presence of anhydrous potassium carbonate gave the corresponding prenyloxycoumarins1d,1e, and1f. The prenyloxy coumarins1d,1e,1f onClaisen migration by refluxing inN,N-dimethyl aniline gave the corresponding 4,4,5-trimethyl-dihydrofuranocoumarins2a,2b, and3. However, the reaction of1a,1b, and1c with 3-chloro-3-methyl-but-1-yne in acetone in presence of potassium carbonate and potassium iodide gave the corresponding propargyl ethers1g,1h,1i, which on refluxing inN,N-dimethyl aniline gave the corresponding 2,2-dimethylchromenopyrans4a,4b, and5. These can also be obtained directly if the reaction is carried out in the presence of dioxan.

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Die Reaktion von 4-Methoxycumarinen mit Prenylbromid: Synthese von 4,4,5-Trimethyl-dihydro-furanocumarinen und 2,2-Dimethylchromenopyranen

Zusammenfassung Die Reaktion von 7-Hydroxy-4-methoxy-(1a), 7-Hydroxy-4,5-dimethoxy-(1b) und 5-Hydroxy-4,7-dimethoxy-2H-1-benzopyran-2-onen (1c) mit Prenylbromid in Aceton in der Gegenwart von wasserfreiem Kaliumcarbonat ergab die entsprechenden Prenylcumarine1d,1e und1f. Diese ergaben durchClaisen-Wanderung bei Rückfluß inN,N-Dimethylanilin die entsprechenden 4,4,5-Trimethyldihydrofuranocumarine2a,2b und3. Die Reaktion von1a,1b und1c mit 3-Chlor-3-methyl-1-butin in Aceton in Gegenwart von wasserfreiem Kaliumcarbonat und Kaliumjodid ergab die entsprechenden Propargylether1g,1h und1i, die ihrerseits bei Rückfluß inN,N-Dimethylanilin die jeweiligen 2,2-Dimethylchromenopyrane4a,4b und5 ergaben. Letztere können auch direkt erhalten werden, wenn die Reaktion in Gegenwart von Dioxan durchgeführt wird.

     

Zur Synthese von 1-(3,3-Dimethyl-2-norbornyl)-äthanon

An improved synthesis of the title compound (1) is described. The catalytical action of variousLewis acids on the sterically hinderedDiels-Alder reaction of mesityl oxide with cyclopentadiene has been investigated. The mixture ofendo- andexo-isomers of the unsaturated intermediate2 yielded pure1 on hydrogenation and isomerization by sodium methoxide. The proof of theexo-configuration of the acetyl group has been achieved by mass spectra and 100 MHz¹H-NMR spectra.

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Herrn Prof. Dr.M. Pailer mit den besten Wünschen zum 65. Geburtstag gewidmet.     

Synthesen von Heterocyclen, 146. Mitt.: Zur Synthese polymerer Indigofarbstoffe mit potentiellen Halbleitereigenschaften

Zusammenfassung Die Darstellung von polymeren Indigofarbstoffen (PI) nach dem Verfahren vonZiegler undKappe ^{2, 3} wird beschrieben. Ausgehend von Benzidin (1 a) und Tolidin (1 b) erhält man so diePI 6 a bzw.6 b. In analoger Weise wird aus Tetrahydrochinoxalin (7), der N,N-überbrücktePI 12 gewonnen.

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Syntheses of heterocycles, CXLVI: The synthesis of polymeric indigos with potential semiconductor properties

The synthesis of polymeric indigos (PI) according to the procedure ofZiegler andKappe ^{2, 3} is described. Starting with benzidine (1 a) or tolidine (1 b) thePI 6 a and6 b, resp., are obtained. In a similar way the N,N-bridgedPI 12 is synthesized from tetrahydroquinoxaline (7).

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Aus den Dissertationen vonH. G. Foraita undL. F. Werner, Universität Graz, Januar bzw. Juni 1963.     

Optisch aktive aromatische Spirane, 7. Mitt. Circulardichroismus optisch aktiver 5,5′-disubstituierter 2,2′-Spirobiindane

Dipole-dipole coupling of the indane fragments in 5,5-disubstituted 2,2-spirobiindanes is predominantly responsible for the origin of optical activity in the¹L_a-electronic transition only if both ligands exhibit strong interaction with the aromatic nuclei. This mechanism does not contribute essentially to the¹L_b-Cotton effect.The band-splittings of the couplet as well as the rotational strengths of the transitions ofA andB symmetry-type in the¹L_a-Cotton effect are in accordance with a rough calculatory estimation.The absolute configuration thus determined agrees with the chirality recently deduced by chemical methods.The rotational strengths of the¹W-Cotton effect of the carbonyl derivatives4, 5, 12, 13, and15 located at appr. 320 nm are remarkably low. This can be explained on the basis of conformational considerations.

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6. Mitt.:H. Neudeck undK. Schlögl, Chem. Ber.110. 2624 (1977).     

Zur gezielten Oxidation der Δ7-Doppelbindung in den 4-Phenyl-1,2,4-triazolin-3,5-dion-Addukten des Vitamin D3

The possibility of regio- and stereospecific oxidation of the 7-double bond of the 4-phenyl-1,2,4-triazolin-3,5-dione adducts1 a and1 b of Vitamin D₃ is reported. Oxidation of the corresponding benzoates2 a and2 b withm-Chlorperbenzoic acid yields the two oxirans3 a and3 b which in turn with NaI-CH₃COOH-Zn after saponification to5 a and5 b lead to the allylic alcohols6 a and6 b.

     

Preparation and stereoselectivity of 1,3-dipolar cycloaddition of C-glycosyl nitrones to N-arylmaleimides

Summary The cycloaddition of 3-hydroxyglycosyl-N-methylnitrone (1) to N-arylmaleimides gave thesyn isoxazolidines6, whereas 3-acetoxyglycosyl-N-methylnitrone (2) afforded theanti isoxazolidines8 and10. The formation of6 was rationalized by anexo attack, stereoelectronically preferred through the hydrogen bond between the pentose hydroxyl group and one of the carbonyl groups of N-arylmaleimide. The sterically preferredendo attack avoiding the repulsions between N-arylmaleimide and sugar moiety was proposed for addition of2. The structure and steric configuration of the products have been assigned on the basis of¹H- and¹³C-NMR spectroscopy, mainly by nuclear Overhauser effect difference spectroscopy. AM1 calculations of the nitrones and MM2 calculations of the adducts were performed.

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Darstellung und Stereoselektivität der 1,3-dipolaren Cycloaddition von C-Glycosyl-Nitronen an N-Arylmaleimiden

Zusammenfassung Die Cycloaddition von 3-Hydroxyglycosyl-N-methylnitron (1) an N-Arylmaleimide gab diesyn-Isoxazolidine6, mit 3-Acetoxyglycosyl-N-methylnitron (2) wurden hingegen dieanti-Isoxazolidine8 und10 erhalten. Die Bildung von6 wurde mit einemexo-Angriff erklärt, der stereoelektronisch wegen einer Wasserstoffbrückenbindung zwischen der Hydroxylgruppe der Pentose und einer Carbonylgruppe des N-Arylmaleimides bevorzugt wird. Für die Addition von2 wurde ein sterisch bevorzugterendo-Angriff vorgeschlagen, da dabei ungünstige Wechselwirkungen zwischen der N-Arylmaleimid- und der Zuckereinheit vermieden werden. Die Struktur und Stereochemie der Produkte wurde mittels¹H- und¹³C-NMR unter Verwendung von NOE-Differenzmessungen ermittelt. Es wurden auch AM1-Rechnungen für die Nitrone und MM2-Rechnungen für die Addukte durchgeführt.

     

Stereochemie vonGrignard-Reaktione mit 2-(N-Methylanikino)-cyclopentanonen

TheGrignard reactions of the 2-anilinocyclopentanones (1 a and1 b) with CH₃MgI and C₆H₅CCMgBr, giving the 2-anilinocyclopentanols2 a, 2 b, and2 c, and the synthesis oftrans-1-methyl-2-(4-chloro-N-methylanilino)-cyclopentanol (4), which was used as a reference compound of known stereochemistry, are described. IR spectroscopic investigations of2 a, 2 b, and2 c as compared with4 lead to the conclusion that2 a, 2 b, and2 c have the structures ofcis-2-(N-methylanilino)-cyclopentanols.     

Über polycyclische 2-Alken-1-on—Guanidin-Kondensate

Guanidine reacts with 1,3-diphenyl-2-propen-1-one to yield not only the dihydropyrimidine2 a ² and the aromatic compound3 a ², but also a bicyclic base, 2,4,6,8-tetraphenyl-2,8-dihydro-1H-pyrimido[1,2–a]pyrimidine (4). Action of 4-phenyl-3-buten-2-one on guanidine generates a 22-condensate, 7-methyl-4,5-diphenyl-4,4a,5,6,7,8,10,10a-octahydro-7,10a-methano-pyrimido[4,5–d]diazocine-2,9(1H, 3H)-diimine12 R besides the methylphenylpyrimidinamine3 b ². The structural formulae4 and12 are proved by NMR-spectra. The mass spectra and the mechanisms of the formation of4 and12 are also discussed.

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Herrn Prof. Dr.O. Hromatka zum 70. Geburtstag gewidmet.     

Molecular dynamics simulations on the protonated 222. H+ and 222.2H+ cryptands in water:Endo versusexo conformations

MD simulations on the 222 cryptand, monoprotonated 222.H⁺ and diprotonated 222.2H⁺ in theendo-endo andexo-exo conformations have been performedin vacuo and in a bath of water molecules. It is found that intrinsicallyendo protonation is favoured overexo protonation due to internal N-H⁺ ... O hydrogen bonding which makes the cage more rigid. On the other hand,endo protonated forms display hydrophobic hydration compared toexo forms. For the monoprotonated 222. H⁺ endo conformer, one water molecule is hydrogen bonded inside the cage thereby forming a water cryptate. From the hydration pattern found previously for the neutral 222 cryptand and for its cation complexes, we suggest mechanisms (not involvingexo toendo conversions) for the protonation of 222 and for acid catalysed decomplexation of cryptates in theendo-endo form.     

Theoretical refinements of theendo and theexo structures of tetraborane(8) carbonyl

The molecular structures of theendo (1a) andexo (1b) isomers of B₄H₈CO have been optimized at the ab initio MP2(Full)/6-31G^* level of theory. The agreement of the computed geometrical parameters with the recently published electron-diffraction (GED) data is very good, even though a number of geometrical constraints were applied in the experimental determination. The IGLO (individual gauge for localized orbitals)¹¹B NMR chemical shifts, calculated at the II//MP2/6-31G^* level, are also in accord with experiment. The formation of1a and1b by association of B₄H₈ and CO is computed to be exothermic by 22.8 and 22.2 kcal/mol, respectively, at the MP2(Full)/6-31G^*//MP2(Full)/6-31G^* + ZPE(6-31G^*) level of theory. The Lewis acid strength of B₄H₈ toward CO is comparable to that of BH₃.     

Reaction of 3-phenyl-5-aminopyrazole with carbon disulfide: A novel synthesis of 3-(3′-phenylpyrazol-5′-yl)-4-phenylpyrazol-2-thione as well as of pyrazolo[3,4-d]thiazole and pyrano[2,3-d]thiazole derivatives

Summary 3-Phenyl-5-aminopyrazole (1) reacts with carbon disulfide, followed byin situ reaction with -haloketones3a–c, to afford5,7a, and7b, respectively. Compounds5 and7 were further utilized for the formation of heterocycles and their fused derivatives.

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Reaktion von 3-Phenyl-5-aminopyrazol mit Schwefelkohlenstoff: Ein neue Synthese von 3-(3-Phenylpyrazol-5-yl)-4-phenylprazol-2-thion sowie von Pyrazolo[3,4-d]thiazol- und Pyrano[2,3-d]thiazolderivaten

Zusammenfassung 3-Phenyl-5-aminopyrazol (1) reagiert mit Schwefelkohlenstoff und anschließendin situ mit den -Halogenketonen3a–c zu5,7a und7b. Die Verbindungen5 und7 wurden weiter zu Heterocyclen und ihren kondensierten Derivaten umgesetzt.

     

Synthese des 4-Hydroxy-6,6-dimethyl-5,6-dihydro-2H-thiopyran-2-thions bzw. -ons und der entsprechenden Tautomeren

The tautomers 4-hydroxy-6,6-dimethyl-5,6-dihydro-2H-thiopyran-2-thione (4 a) and 2-mercapto-6,6-dimethyl-5,6-dihydro-4H-thiopyran-4-one (4 b) resp. were synthesized by hydrolysis of 4-amino-5,6-dihydro-2H-thiopyranthiones6,8. On methylation of4 a,b only the S-methyl product7 is formed. Hydrolysis of 4-amino-2-methylthiothiopyranyliden iodides11 leads—depending on the amino group of11—either to the thiopyranone7 or to the 4-imino-thiopyranes12 and to -amino-,,,-unsaturated-methyldithio carboxylates13. On reaction of4 a,b with hydrogenperoxyd the tautomers 4-hydroxy-5,6-dihydro-2H-thiopyran-2-one5 a and 5,6-dihydro-2H-thiopyran-2,4(3H)diones5 b resp. are formed.4 a,b and5 a,b undergo an aminolysis with prim. and sec. amines to the corresponding 4-amino-2H-thiopyran-2-thiones6,8 and -ones10 resp. On heating in alcohols the 4-alkoxy-thiopyrane-2-thiones and -ones9,14 are formed from4 a,b and5 a,b resp.

     

Basische Tetrahydro-dibenzofuran-Derivate mit einem Abstand von drei C-Atomen zwischen dem Stickstoff und dem quartären C-Atom

Pummerer's ketone (1) is a pharmacophoric synthon, which can be used for a great number of synthetic variations. We have investigated the insertion of basic groups into C-1, C-2 and C-3. TheClaisen rearrangement of the allylic alcohols2 a and2 b leads to3 a and3 b, the reduction of which produces4 a and4 b. TheMannich reaction of1 unexpectedly gives the 2-aminoalkylcompounds7 c-j and the synthesis of the derivatives2e-j was performed by aminolysis of the 3-chloro-compound2 d.     

Enhanced reactivity of secondary hydroxyl groups in the O-alkylation of carbohydrate-related primary-secondaryvic-glycols. Regioselective 2-O-benzylation of 1,3:2,4-di-O-ethylidene-D-glucitol

Partial O-alkylation of 1,3:2,4-di-O-ethylidene-D-glucitol (1a), 1,2-O-isopropylidene-3-O-methyl--D-glucofuranose (1b), andR-(+)-1-O-benzylglycerol (1c) with benzyl chloride in a KOH/DMSO system results in products of monoalkylation at the secondary (4a–c) and at the primary hydroxyl (2a–c) in ratios of over 955 (a), 21 (b), and 11 (c), whereas (±)propane-1,2-diol (1d) gives only the product of 1-O-benzylation (2d). A qualitatively similar result is observed upon O-alkylation of diols (1a–e) with 2-methoxyethanol tosylate.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 776–781, April, 1993.     

2-Amino-1-cyan-glutaconsäureamid-1-methylester,ein Dimeres des Cyanessigesters und Cyanacetamid

Synthesis of methyl 3-amino-4-carbomyl-2-cyano-2-butenoate is described and2 a classified as a dimer of methyl cyanoacetate and cyanoacetamide. By ammonolysis of the dimer of methyl cyanoacetate with dimethylamine and anilines, resp. the dimethylamide and anilides, resp. (2 b and3 a–j) are obtained. Condensation with salicylaldehyde to the pyrone derivative4 proves the structure of2 a, ring closure reactions in basic or acidic medium yield the pyridones6 a and7 a,b, coupling with diazonium salts the pyridazines8 a–d. The amides2 and the anilides3 show hindered rotation of the enamino- and the amide-group by hydrogen bonds between the nitrogen functions and the ester carbonyl (Z-form). The G values are reported.

     

Synthesis of some schiff bases of 3-aroyl-6-aryl-4-hydroxy-2H-pyran-2-ones

Summary The reaction of 3-aroyl-6-aryl-4-hydroxy-2H-pyran-2-ones (Ar=p-tolyl, 1,1-biphenyl-4-yl or thienyl) with aniline and substitutedo-phenylenediamine (R=H, CH₃ or Cl) yields a series of new Schiff bases2a–f in 51–72% yield. Bromination of1a gave the 5-bromo derivative1c, while the compounds1a,1b,2b,2e, and2f were converted into 2,6-diaryl-4H-pyran-4-ones3a–c. All products have been fully characterized.

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Synthese von Schiff'schen Basen von 3-Aroyl-6-aryl-4-hydroxy-2H-pyran-2-onen

Zusammenfassung Die Reaktion von 3-Aroyl-6-aryl-4-hydroxy-2H-pyran-2-onen (Ar=p-Tolyl, 1,1-Biphenyl-4-yl oder Thienyl) mit Anilin und substituierteno-Phenylendiaminen liefert neue Schiff'sche Basen2a–f/bd in 51–72% Ausbeute. Bromierung von1a gab das 5-Bromderivate1c, während die Verbindungen1a,1b,2b,2e und2f in 2,6-Diaryl-4H-pyran-4-onen3a–c übergeführt wurden. Alle Produkte wurden voll charakterisiert.