Bibliothek

Notizen: Azimines. IITeil I, siehe [1]. . Preparation and Thermal Fragmentation of cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine Teilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft am 8./9. Oktober 1976 in Genf und als Autoreferat veröffentlicht [2].cis- and trans-2,3-Diphenyl-1-phthalimido-2,3-di[15N]-azimine (11 and 12) wer synthesized from cis-di[15N]-azobenzene (10) and phthalimido-nitrene (2), the latter generated by lead tetraacetate oxidation of N-aminophthalimide (1). Useful information was obtained from the comparison of several data of 11 and 12 with those of the unmarked diphenyl-azimines 5 and 6 (R = C6H5).The 15N- and 13C-NMR. spectra of 11 and 12 were interpreted to furnish additional evidence for the azimine structure and for the indicated configurations. The IR. spectra permitted identification of two bands in the 1200 to 1450 cm-1 region, probably characteristic for the functionality of diaryl-phthalimido-azimines. Comparison of the mass spectrum of 11/12 with that of the unmarked analogues 5/6 (R = C6H5) permitted the interpretation of the fragmentation path of 1-phthalimidoazimines. The major path may be the purely thermal decomposition to 13 and 7 (R = C6H5), respectively. Two other competing fragmentation paths are discussed.Prolonged thermolysis of 11 at 61° in solution gave 83% of N,N′-diphenyl-N N′-phthaloyl-di[15N]-hydrazine (13) of 98% isotope purity, which means that the imide nitrogen atom and N(1) of the azimine function are removed in this reaction. A mechanism passing through an intermediate cyclic tetrazene 16 is considered.Benzocyclobutenedione (14) added to trans-azobenzene (4, R = C6H5) under the influence of a high pressure lamp in a quarz apparatus to give N,N′-diphenyl-N,N′-phthaloyl-hydrazine (7, R = C6H5). This reaction was found not to take place in the dark, even after prolonged heating in trichloromethane.

Notizen: Azimines. I. Synthesis and Stereoisomerism of 2, 3-Diaryl- and 2, 3-Dialkyl-1-phthalimido-aziminesTeilweise vorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Lausanne am 7./8. Mai 1971 und als Autoreferat veröffentlicht [1].Special examples of a new class of compounds, the open-chain azimines (1), have been prepared and their properties examined.Addition of phthalimido-nitrene (4), generated by lead tetraacetate oxidation of N-aminophthalimide (3), to cis- and trans-azobenzene (6 and 5), -azo-p-toluene (8 and 7), and to trans-azomethane (9), -azoethane (10) and -azo-α-phenylethane (11) afforded the separable cis- and trans-isomers of 2, 3-diphenyl- (12 and 13), 2, 3-di-p-toyl- (14 and 15), 2, 3-dimethyl- (16 and 17), 2, 3-diethyl- (18 and 19) and 2, 3-di-(α-phenylethyl)-1-phthalimido-azimines (20 and 21) in different ratios (see Scheme 1).The constitution of the nitrene azo compound adducts as azimines was derived from their properties, especially from the conjugation effect (visible in the UV. spectra) of the aryl-substituted compounds and from the non-equivalence (shown by the 1H-NMR. spectra) of the substituents on the two nitrogen atoms derived from the azo compounds. This evidence excluded the triaziridine 22 and an alternative azimine constitution 23 for the adducts.Of the two stereoisomers obtained for each of the azimines, the aryl-substituted examples 12/13 and 14/15 were readily interconverted by warming in solution, the cis-isomers 12 and 14 exceeding the trans-isomers 13 and 15 in the equilibrium. The dialkyl-azimines appear to be configurationally more stable, since interconversion of the dimethyl-azimines 16 and 17 was not possible under the same conditions, and also not before another thermal reaction took place (see below).The identification of the N(2)-N(3) bond as the stereogenic center, i.e. that the stereoisomerism of the azimines is due to the difference in relative position at N(2) and N(3) of the substituents derived from the azo compounds, as well as a configurational assignment was possible in the aryl-substituted examples on the basis of the UV. spectroscopic comparison of the isomeric azimines with the corresponding stereoisomeric azoxy compounds: The cis-azimines 12 and 14 showed absorptions similar to those of cis-azoxybenzene and cis-azoxy-p-toluene, and the trans-azimines 13 and 15 showed absorptions similar to those of the respective trans-azoxy compounds. With respect to the configuration of the alkyl-substituted azimines, it was observed that the isomers 17 and 19, which from their formation and chromatographic behaviour are likely to be the trans-isomers, show a visible coupling (∽ 1 Hz) between the two H (α)'s in the 1H-NMR. spectrum, whereas the dimethyl isomer 16 (cis) does not exhibit such a coupling.Thermal treatment of four azimines, namely 12, 14, 16 and 17, in solution for a longer time afforded the corresponding N, N′-disubstituted N, N′-phthaloyl-hydrazines 27, 28 and 29. The order of velocity of this fragmentation with nitrogen extrusion was 12/13 ≍ 14/15 〉 16(cis) 〉 17(trans).

Notizen: Reaktionen von 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]octan-2,6-diolen und deren 4,4,8,8-Tetrachlor- und 4,8-Dichlorderivaten mit DiphosphortetrajodidEs wurden die P2I4-Reaktionen mit 1,3,5,7-Tetramethyl-anti-tricyclo[5.1.0.03,5]-octan-2,6-diolen (3/6), mit dem 4,8-Dichlorderivat 4 und mit den 4,4,8,8-Tetrachlorderivaten 5/7 untersucht. Dabei entstanden die Styrolderivate 9 und 12, die anti-Bishomobenzolderivate 8 und 11, ein Homotropylidenderivat 10, ein Cyclo-octatetraenderivat 13 und ein 9-Oxabicyclo[4.2.1]nona-2,4,7-trienderivat 15. Die Ausbeuten lagen zwischen 1 und 10%. Die Bildung aller dieser Produkte liess sich unter der Annahme der primären Umwandlung einer oder beider Hydroxylgruppen in Abgangsgruppen X oder X und Y (wahrscheinlich X=Y=I) mechanistisch deuten. Die Reaktion der Deschlorderivate 3/6 lieferte nach Substitution beider Hydroxyl-gruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 9 (Schema 2) und (b) unter Abspaltung von XY das Homotropylidenderivat 10 (Schema 3a) und das Bishomobenzolderivat 8 (Schema 3b). Die Reaktion des 4,8-Dichlor-derivates 4 lieferte nach Substitution beider Hydroxylgruppen durch X und Y: (a) unter Abspaltung von HX und HY das Styrolderivat 12 (Schema 2), und (b) unter Abspaltung von XY das Bishomobenzolderivat 11 (Schema 3b). Die Reaktion mit den 4,4,8,8-Tetrachlorderivaten 5/7 lieferte: (a) nach Substitution beider Hydroxyl-gruppen durch X und Y unter Abspaltung von XCl und YCl das Cyclooctatetraen-derivat 13 (Schema 4), und (b) nach Substitution nur einer Hydroxylgruppe durch X unter Abspaltung von XCl und HCl das bicyclische Derivat 15 (Schema 5). Alle diese Reaktionen sind zusätzlich zu den angegebenen Fragmentierungen und Eliminierungen noch teilweise von Umlagerungen des Kohlenstoffgerüstes begleitet.Die thermische Umlagerung von 1,5-Dichlor-2,4,6,8-tetramethyl-cycloocta-1,3,5,7-tetraen (13) in das Styrolderivat 12 wurde in Abhängigkeit der Lösungs-mittelpolarität untersucht und mit der analogen thermischen Umlagerung von Brom-cyclooctatetraen und Chlor-cyclooctatetraen verglichen.

Notizen: Synthese von 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentanal und dessen Umwandlung in Spiro[4.5]decan- und 1,6,7,7a-Tetrahydro-2H-inden-DerivateEs wird die Synthese von 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentanal als ein (1:1)-Gemisch von zwei Diastereoisomeren 10A und 10B auf folgendem Weg beschrieben: Die Umsetzung des Grignard-Reagens von 1,1-Äthylendioxy-3-brom-propan (2) mit 2-Methoxy-4-methyl-acetophenon (1) ergab 1,1-Äthylendioxy-4-hydroxy-4-(2′-methoxy-4′-methyl-phenyl)-pentan (3), welches sich mit methanolischer Salzsäure in 2-Methoxy-5-(2′-methoxy-4′-methyl-phenyl)-5-methyl-tetrahydrofuran (7A,B) umwandeln liess. Durch Birch-Reduktion von 7A,B wurde 4-(2′-Methoxy-4′-methyl-cyclohexa-1′,4′-dien-1′-yl)-pentan-1-ol (8), und danach durch milde Hydrolyse 4-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentan-1-ol (9A,B)2 erhalten. Oxydation von 9A,B lieferte schliesslich den erwähnten Keto-aldehyd 10A,B. Einige Produkte von Nebenreaktionen, nämlich 4, 5, 11, 12 und 13A,B, sind auch beschrieben.Der Keto-aldehyd 10A,B liess sich in ein Gemisch, bestehend aus drei Diastereo-isomeren A, B und C von 1-Hydroxy-4,8-dimethyl-spiro[4.5] dec-7-en-6-on (15) und aus zwei Diastereoisomeren A und B von 1,5-Dimethyl-1,6,7,7a-tetrahydro-2H-inden-3-carbaldehyd (14), umwandeln. Für diese aldolartigen Cyclisierungen wurden vier verschiedene Methoden verwendet: (a) Stehenlassen in Tetrachlorkohlenstoff-lösung, (b) Behandlung mit etwas Trifluoressigsäure in Chloroformlösung, (c) und (d) Schütteln einer Ätherlösung mit wässeriger Salzsäure oder Natronlauge. Oxydation von 15A und 15C lieferte eines der Diasteroisomeren von 4,8-Dimethyl-spiro[4.5]-dec-7-en-1,6-dion (16A), und Oxydation von 15B führte zum anderen (16B).

Notizen: Synthese und Umlagerung von 7-Halo-bicyclo[3.2.0]hept-2-en-6-olenDie Reaktion von verschiedenen 7-halogen-substituierten Bicyclo[3.2.0]hept-2-en-6-onen mit komplexen Metallhydriden oder mit Methylmagnesiumiodid zu den entsprechenden 7-Halo-bicyclo[3.2.0]hept-2-en-6-olen verläuft unter Angriff des Nucleophils trans zum Halogen, um dem vicinalen Kohlenstoff-Halogen-Dipol auszuweichen. In Gegenwart von starken Basen unterliegen die Halohydrine einer Umlagerung, die je nach der durch die intramolekularen Wechselwirkungen bedingten Konformation, entweder unter Hydridverschiebung zu Bicyclo[3.2.0]hept-2-en-6-onen oder, unter Ringverengung, zu Bicyclo[3.1.0]hex-2-en-6-carbaldehyden führt.

Notizen: Bildung von 5-Hydroxy-indan-2-on bei Hydrolyseversuchen mit 9-Äthylendioxy-bicyclo[3.3.1]nonan-3,7-dionVerschiedene Versuche, 9-Äthylendioxy-bicyclo[3.3.1]nonan-3,7-dion (2) durch Hydrolyse in das entsprechende Triketon 3 umzuwandeln, führten nur zu 5-Hydroxy-indan-2-on (4) und in einem Fall auch noch zu etwas 7,9-Bis(äthylendioxy)-bicyclo-[3.3.1]nonan-3-on (5). Unter milderen Hydrolysebedingungen reagierte 2 gar nicht.Die Bildung von 4 aus 2 wird über eine Wagner-Meerwein-Umlagerung und nach-folgende Eliminierung von Äthylenglycol formuliert. Das so entstandene Äthylenglycol reagiert mit noch vorhandenem Acetal 2 zum Bis-acetal 5, was als weitere Bestätigung der Resistenz von 2 gegen Hydrolyse gelten darf.

Notizen: The Aminal-enamine Equilibrium in Cyclopropane-carbaminals.The following cyclopropane-carbaminals were synthesized: N,N′-(T-2,t-3-dimethyl-r-1-cyclopropyl)methylene-dipyrrolidin (15), the corresponding (c-2, c-3)-isomer 16, N,N′-(cyclopropyl)methylene-dipyrrolidin (17) and N,N′-(c-2, t-3-diphenyl-r-1-cyclopropyl)methylene-dipyrrolidin (18). Their constitutions and configurations were derived from the method of synthesis and from 1H-NMR.-spectra. The c-c-r-1-dimethyl-aminal 16 rearranged at room temperature to its t-t-r-1-dimethyl-isomer 15. This demonstrates the existance of an aminal-enamine equilibrium for cyclopropane-carbaminals although cyclopropane-carbenamines have not been isolated as yet. The kinetic data found for the rearrangement of 16 to 15 are compatible with two mechanisms: In the first one, the protonated aminal 21 decomposes into the iminium-ion 22, which, in turn, yields the enamine 19. In the second one, 21 is converted to 19 in a single step. The formation of cyclopropyl-pyrrolidino-acetonitrile (26) and dipyrrolidino-ethylene-1,1-dicarbonitrile (27) from the reaction of the aminal 17 with tetracyanoethylene may also be explained with an aminal-enamine equilibrium. - This equilibrium lies strongly on the side of the aminal. Investigations of the aminal-enamine ratio of several cycloalkanecarbaminals, namely of the 3-ring derivative 17, the 4-ring derivative 35 and the bicyclic 5-ring derivative 38, show that ring strain is a determining factor for the equilibrium bias. This strain may also explain that the aminomethanol 41 was isolable.Some of the aminals were synthesized from previously unknown aldehydes. t-2, t-3-dimethyl-r-1-cyclopropane-carbaldehyde (11) and its (c-2, c-3)-isomer 12 were obtained by stereoselective ring-contraction of the 2-chloro-cyclobutanols 46 and 48/49, respectively. The configurations of the aldehydes 11 and 12, of the starting cyclobutanones 44 and 45 and of the cyclobutanol 46 were established by 1H-NMR. measurements. From the steric course of the ring contraction it can be concluded that it is the fastest rearrangement of 2-halo-cyclobutanols with base, when the conformation having an equatorial halogen atom is not obstructed. c-2, t-3-diphenyl-r-1-cyclopropane-carbaldehyde (14) and 3-phenyl-1-cyclobutane-car-baldehyde (34) were synthesized by reduction of the corresponding ester 50 and acid 52, respectively, followed by Sarett-oxidation.

Notizen: Rearrangement of Vinyl-Cyclopropane-CarbaminalsBoth (c-2, t-3-diphenyl-r-1-cyclopropyl)methylene-dipyrrolidine (4) and its (t-2, t-3)-isomer 10 underwent a thermal rearrangement to (E)-N-2-benzylidene-1-indanyl-pyrrolidine (5). Under the conditions of the rearrangement, 5 was partially converted into 2-benzyl-1-indanone (6) in a base catalysed reaction. The structures of 5 and 6 were derived from spectroscopic data and from degradation reactions.- N,N′-(t-2-Vinyl-r-1-cyclopropyl)methylene-dipyrrolidine (11) rearranged thermally to N-(2-methylidene-3-cyclopenten-1-yl)pyrrolidine (12), the structure of which was established from spectroscopic evidence and from a hydrogenation to N-(2-methylcyclopentyl)pyrrolidine (13, cis/trans mixture 3:2).The aminal 4 was reduced with formic acid to give N-(c-2, t-3-diphenyl-r-1-cyclopropyl)methyl-pyrrolidine (14). If perdeuterio formic acid was used, the mixture product 14-d/14-d2 was obtained which contained exactly one deuterium atom in its methylene group and about half a deuterium atom on C(1). This labeling pattern is mechanistically explained with the existence of a fast equilibrium between the iminium ion 19 and the enamine 18, so that 18 and 19 are considered to be plausible reactive intermediates in the above mentioned thermal rearrangement. - Based on this, several mechanisms for the rearrangements 4 → 5, 10 → 5 and 11 → 12 were considered: A Pictet-Spengler- or Mannich-type reaction, which starts from the iminium ion 23 and is followed by a cyclopropylmethyl-homoallylic rearrangement and by deprotonation (path a, Scheme 5), was judged to be improbable because the postulated intermediates could lead more easily to other stable products than the observed ones. If the reaction is formulated as a [3,3]-sigmatropic shift occurring on exclusively the (E)-isomer 5 suggests a concerted process whose steric course is predominantly controlled by strain factors. Alternatively, the reaction could be formulated via a dipolar (27) or a diradical (26) species derived from the enamine 22 (paths c and d, Scheme 5); attempts to trap such species by a number of agents were unsuccessful. - The previously unknown aminals 10 and 11 were synthesized by standard methods.

Notizen: The Formation of Cyclopentadecane-1,5-dione Derivatives by an Oxiranylmethyl Fragmentation. A Synthesis of MusconeA new method for the preparation of cyclopentadecane-1,5-dione (11) and its 3-methylderivative 12, compounds with a musk fragrance, is described. Starting from the readily available bicyclic enones 9 and 10, the epoxy-p-toluenesulfonate 15 and its methylderivatives 20A and 20B were prepared by reduction with diisobutyl-aluminium hydride or sodium borohydride (to 13 and 18A, 18B), epoxidation with m-chloroperbenzoic acid (to 14 and 19A, 19B), followed by tosylation. Heating of 15 and 20A or 20B with calcium carbonate in water/dioxane under reflux caused fragmentation leading to the diketones 11 and 12 in high yields. The same fragmentation also occurred with sodium hydrogencarbonate in dimethylsulfoxide at 160°, but in lower yields. The conversion of 12 into rac-muscone (2) was accomplished by developing a method for selectively forming the monotosylhydrazone 27. The latter was reduced with sodium borohydride and the crude alcohol 28 oxidized to 2.Unexpectedly the pyrolysis of the epoxy-acetate 29 at 350° in a sealed glass tube led to the bicyclic ketone 10. Treatment of 3-methylcyclopentadecane-1,5-dione (12) with peracetic acid and boron trifluoride etherate gave the stable crystalline ozonide 33.

Notizen: Syntheses and Thermolyses of 1-Alkynyl-2-methyl-1,2-epoxy-cycloalkanes. - Attempts at Ring Enlargement by Three Carbon AtomsThe 1-alkynyl-2-methyl-1,2-epoxy-alkene 2 and -cycloalkenes 9, 28 and 29 were obtained by epoxidation of the conjugated en-ynes 1, 7, 26 and 27. The 12-membered ring en-ynes 26 and 27 were synthesized by ethynylation or propynylation of 2-methylcyclododecanone (19) to the 1-ethynyl- or 1-(1′-propynyl)-cyclododecanols 20 A/B and 21 A/B, respectively, followed by dehydration to give separable mixtures of the regio- and stereoisomeric en-ynes 22, 24, 26 and 23, 25, 27, respectively.Gas-phase thermolyses of the epoxides 2, 9, 28 and 29 were carried out under reduced pressure through a quartz tube at 550-600°. The formation of 5-hexine-2-one (3) and 4,5-hexadien-2-one (4) from 2 can be explained by [1, 5]- and [1, 3]- hydrogen shifts, respectively, and subsequent Claisen-type rearrangements. Thermolysis of the six-membered carbocyclic epoxide 9 induced the expected ring expansion by three carbon atoms to give 14% 4-cyclononynone (12), along with the ketones 13, 14 and 15 as by-products, which probably arose from surface induced heterolytic C, O-bond fission and Wagner-Meerwein-type rearrangement processes.Preliminary experiments with the thermolysis of the 12-membered carbocyclic ethynyl-epoxide 28, yielded a mixture, which contained 4-cyclopentadecynone (30) and afforded, after hydrogenation, cyclopentadecanone (31, exaltone®) in 36% yield as the semicarbazone. Traces of 3-methylcyclopentadecanone (32, rac, -muscone) were identified after thermolysis and hydrogenation of the propynyl-epoxide 29.