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Notes: Summary An i.v. injection of 548 μg of killedCorynebacterium parvum into C57B1 mice leads to significant changes in serum lysozyme (muramidase) levels. After an initial fall at 24 h, the activity of the enzyme increased progressively, reached a peak on the 9th day and returned to control range after the 15th day.

Notes: Eine spezifische Synthese von (2Z)-2-Brommethyl-2-butensäure-äthylester und seine Umwandlung in Mikanezester.Das Lithiumsalz 12, hergestellt aus 2-Bromorthopropensäure-triäthylester (11) und n-Butyl-lithium, wurde mit Acetaldehyd umgesetzt, wobei 2-Methyliden-3-hydroxy-orthobutansäure-triäthylester (13) und daraus, durch saure Hydrolyse, 2-Methyliden-3-hydroxybutansäure-äthylester (14) entstand. Behandlung von 14 mit N-Bromsuccinimid und Dimethylsulfid lieferte den gewünschten (2Z)-2-Brommethyl-2-butensäure-äthylester (6), der sich mit HBr zur entsprechenden Säure 4 hydrolysieren liess.Die (2Z)-Konfiguration von 4 wurde aufgrund der vicinalen 1H/13C Kopplungen zwischen H-C(3) und COOH bzw. CH2Br im 13C-NMR.-Spektrum bestätigt. Die 1H-NMR.-Signale der beiden Methylidenprotonen in 9, 11, 13 und 14 liessen sich mit Hilfe von additiven Entschirmungsbeiträgen der Substituenten um die Doppelbindung zuordnen.1,4-Eliminierung von HBr aus (2Z)-2-Brommethyl-2-butensäure-äthylester (6) mit Kalium-t-butylat ergab Mikanezsäure-diäthylester (21), der bei der Aufarbeitung teilweise zum Monoester 20 und zur MikanezsäureThe systematic name for mikanecic acid (19) is 4-vinyl-1-cyclohexene-1,4-dicarboxylic acid.( 19) verseift wurde.

Notes: 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.

Notes: Conversion of the Diastereoisomeric 12-and 6-membered 1-Acetyl-2-methyl-1-cycloalkanols to 1-Ethynyl-2-methyl-1-cycloalkenesThis paper is concerned primarily with a derivation of the E-configuration of 1-ethynyl-2-methyl-1-cyclododecene (10), which plays a role in mechanistic considerations on a method for ring expansion by 3 carbon atoms described in apreceding paper [1]. The derivation is based on an argument using the results of the dehydration of trans-1-acetyl-1-2-methyl-1-cyclododecanol (4) to 10 with phosphorus oxychloride and pyridine. That this dehydration is stereospecific can be concluded from its regiospecificity since the cis-hydroxyketone 3 dehydrates mainly to 1-ethynyl-12-methyl-1-cyclododecene (mixture of stereoisomers 11 and 12). An x-ray analysis shows the indicated configurations of the two hydroxyketones 3 and 4.The direction (anti) of the stereospecificity of the double bond introduction during the 4→10 conversion is deduced from the similarity of the behaviour of the two stereoisomeric 1-acetyl-2-methyl-1-cyclohexanols 8 and 9 under the same conditions and from mechanistic considerations, which make it likeley that the anti-elimination behaviour observed in the 6-membered system has not changed over to a syn-elimination behaviour in the 12-membered system. The configurations of the two 6-membered hydroxyketones 8 and 9 correspond to those of the precursor1-ethynyl-2-methyl-1-cyclohexanols 6 and 7, which were clarified with the help of 13C-NMR.-spectral coupling observations.It is of interest that the hydroxyketones 3, 4, 8 and 9 react with phosphorus oxychloride and pyridine so as to introduce both a double and a triple bond. It is probable that the double bond is introduced first, inasmuch as the triple bond is not introduced in the absence of activation of the hydroxyl group, as for instance in acetylcyclohexane. This can be used as an argument that the conversion of the acetyl to an ethynyl group in 3, 4, 8 and 9 does not affect the stereospecificity of the dehydration which introduces the ring double bond.1-Acetyl-2-methyl-1-cyclododecene (24), a previously isolated compound with pleasant odor, was synthesized by hydration of 10. This furnishes an argument for the E-configuration of 24.

Notes: Es wird über eine, bzw. zwei Methoden zur Herstellung von 4-(4′ Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-pentan-1-ol (Schema 1) bzw. 3-(4′-Methyl-2′-oxo-cyclohex-3′-en-1′-yl)-butan-1-olThe IUPAC-Nomenclature of these compounds is: 6-(4′-hydroxy-1′-methyl-butyl)-3-methyl-cyclohex-2-en-1-one and 6-(3′-hydroxy-1′-methyl-propyl)-3-methyl-cyclohex-2-en-1-one.-Derivaten ( Schemata 2 und 3) berichtet. Die Synthesen sind nicht spezifisch bezüglich Diastereoisomerie an den Zentren C(1′) und C(4), bzw. C(1′) und C(3). Als potentielles Terpenoid-Synthon kommt das Produkt der Synthese nach Schema 1 , Schritte (1) bis (3), in Frage.

Notes: Lead tetraacetate oxidation of N-aminophthalimide (11) in inert solvents gives as major products phthalimide (15) or trans-1,4-bisphthaloyl-2-tetrazene (12), the former (15) on slow, the latter (12) on fast addition of the oxidizing agent. As by-products are found: (a) in the presence of acetic acid: N-acetylamino-phthalimide (14), and (b) in its absence (especially at higher temperatures): benzocyclobutenedione (13) along with N-phthalimido-phthalimide (16) as well as traces of phthalic anhydride (17).The tetrazene 12 and phthalimide (15) are considered to be formed by oxidation and fragmentation, respectively, of the intermediate 1,4-bisphthaloyl-tetrazane (18). Phthalimido-nitrene (22), or its conjugated acid 23, is postulated to be the species which initiates the major reactions, namely: (a) addition to the educt 11 to give the tetrazane 18 and (b) fragmentation with loss of N2 to give the dione 13. The minor by-products 16 and 17 may be the result of cross-amidation of 11 with 15 and rearrangement-oxidation via phthalazine-1,4-dione (30), respectively.The structure of the tetraacyltetrazene 12 follows from its properties, among others a comparison of its UV. spectrum with that of the known 1,4-dimethoxycarbonyl-1,4-dimethyl-2-tetrazene (32). Methanolysis of 12 affords 1,4-di-(o-methoxycarbonyl-benzoyl)-2-tetrazene (33). The diacyltetrazene 33 is converted to methyl N-methoxycarbonyl-anthranilate (36), N2 and phthalimide (15) on thermolysis, or to methyl N-acetylphthalamate (35), methyl N, N′-carbonyldianthranilate (37) and methyl N-acetyl-anthranilate (38) on acetylation in pyridine. The intermediate in these reactions, leading to 36, 37 and 38, probably is o-methoxycarbonyl-phenylisocyanate (34), itself the result of a Curtius-type rearrangement. Acetolysis of the tetrazene 12 gives phthalimide (15), N2 and N-carboxyanthranilic anhydride (42) by a mechanism analogous to that of the methanolysis of 12.In the preparation of 1,4-dimethoxycarbonyl-1,4-dimethyl-2-tetrazene (32), required for the above mentioned comparison, by zinc reduction of methyl N-methyl-N-nitro-carbamate (43), followed by bromine oxidation of methyl N-amino-N-methylcarbamate (44), a deamination of 43 to methyl N-methyl-carbamate (45) was observed both in the reductive and in the oxidative step. Both formations of 45 can be formulated via a nitrene and a tetrazane, namely via 47 and 48.

Notes: A total synthesis of betalaine pigments (6) is described. The key intermediate is betalamic acid in the form of its dimethyl ester semicarbazone (9), which was transformed with L-proline (16) into indicaxanthine dimenthl ester (5), with L-cyclodopa methul ester (17) into betanidine trimethyl ester (3) and by hydrolysis of the latter into betanidine (2).

Notes: 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).

Notes: 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.