ALBERT

Notizen: Synthesis and reactions of the valence polaromeric compound (4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate ⇌ 1-dimethylthiocarbamoyl-1-methyl-ethyl isothiocyanate from 3-dimethylamino-2,2-dimethyl-2H-azirine and carbon disulfide.3-Dimethylamino-2,2-dimethyl-2H-azirine (1) reacts with carbon disulfide to give crystals which have the dipolar structure 3a [(4,4-dimethyl-2-thiazoline-5-dimethyliminium)-2-thiolate, Scheme 1]. In solution, the non-dipolar (charge-free) isomeric form 3b (1-Dimethyl-thiocarbamoyl-1-methyl-ethyl isothiocyanate) is almost exclusively populated. Reaction products are derived from both forms: Derivatives of 3a are the hydrolysis product 6, the sodium borohydride reduction product 7 and the methylation products 9 and 10, respectively (Scheme 2). The isothiocyanate form 3b is responsible for the various reaction products with amines (Scheme 3). One of the reaction products with ammonia, namely 20, is also obtained by the reaction of 1 with thiocyanic acid.Thermolysis of the azirine/carbon disulfide adduct 3 leads to 2-dimethylamino-4,4-dimethyl-2-thiazoline-5-thione (17) in high yield. A possible mechanism is outlined in Scheme 4. The same compound is also formed by rearrangement of 3 under the catalytic influence of dimethylamine. Its structure has been established by X-ray crystallography (section 4). Again a rearrangement is involved in the reductive (NaBH4) conversion of 17 to 7, the direct reduction product of the dipolar species 3a (Scheme 5).The isothiocyanate form 3b is able to react with a second molecule of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) to yield compound 25, which in the crystalline or dissolved state appears to be almost entirely populated by the carbodiimide form with structure 25b (Scheme 7), though all reaction products of 25 (reduction with sodium borohydride, addition of water or hydrogen sulfide, Schemes 7 and 8) are derived from the dipolar form 25a, not detectable as such; here again therefore there is a dynamic equilibrium 25a ⇌ 25b.The two forms of adduct 3, namely 3a and 3b, are obviously very easily interconverted at room temperature and therefore can be considered as valence polaromeric forms (section 5). A classification of the dipolar (zwitterionic) form is given, which allows a comparison of various dipolar species and gives as indication of charge stabilization by delocalization.The versatile reactivity of the 3-dimethylamino-2,2-dimethyl-2H-azirine/carbon disulfide adduct is demonstrated by the fact that with simple reagents approximately 25 derivatives have been obtained, most of them being new heterocyclic compounds.

Notizen: Investigations on the distribution of the stereoisomeric muscarines within the order of agaricales.Stereomeric muscarines (muscarine, epi-muscarine and allo-muscarine), albeit in low concentrations (≤ 2 mg/100 g dry weight), have been found in fruiting bodies of the following species of agaricales: Amanita pantherina, Amanita phalloides, Boletus calopus, Boletus luridus, Clitocybe dealbata, Clitocybe hydrogramma, Clitocybe gibba (= Cl. infundibuliformis s.s. auct. plur.), Clitocybe vermicularis, Clitopilus intermedius, Collybia peronata, Hygrocybe mgrescens, Hypholoma fasciculare, Lactarius rufus, Lactarius trivialis, Mycena pelianthina, Mycena pura, Paxillus involutus, Rhodophyllus rhodopolius, Rhodophyllus sinuatus, Russula emetica, Tricholoma sulphureum, Tylopilus felleus. Collections of the same species from different sites showed pronounced variation in the relative amounts of stereoisomers, e.g. with Clitocybe dealbata and Rhodo phyllus rhodopolius. epi-allo-Muscarine could not be detected in any of the species tested.

Notizen: Preparation of heterocyclic substituted styryl derivatives of 2H-1,2,3-triazole.Anile aus 2-Phenyl-4-formyl-2H-1,2,3-triazolen und o-oder p-Chloranilin können mit p-tolyl-substituierten aromatischen Heterocyclen in Gegenwart von Dimethylformamid und Kaliumhydroxid bzw. Kalium-t-butylat in die entsprechenden heterocyclisch substituierten Styryl-Verbindungen übergeführt werden («Anil-Synthese»). Zur Erzielung guter Ausbeuten muss das Reaktionsgemisch anfänglich mit ultraviolettem Licht bestrahlt werden. Die Darstellung heterocyclisch substituierter 4-(2H-1,2,3-Triazol-2- bzw. -4-yl)-styrol-Verbindungen gelingt mit Natriummethylat ohne UV.-Licht.

Notizen: Metabolites from Microorganisms. 160th Communication. Conocandin, a new Fungistatic Antibiotic.From a strain of Hormococcus conorum (SACC. ET ROUM.) ROBACK A 32′287, conocandin, a novel type C18-fatty acid with high and specific in vitro fungistatic activity was isolated by means of counter current distribution and silicagel chromatography. The antibiotic is a viscous oil with the molecular formula C18H30O3. It is characterized by IR. and NMR. spectra, ester derivatives and the products of acid rearrangement and ozonolytic degradation. The structure of (E)-2-methylidene-10-methyl-trans-3,4-epoxy-9-hexadecenoic acid (1) is proposed.

Notizen: The reaction of singlet oxygen with 2-phenylnorbornene (1) in aprotic solvents gives 3-formylcyclopentyl phenyl ketone (2) (10%) and uncharacterized polymer (90%). When methanol is used as solvent, endo-2-phenyl-exo-2-methoxy-exo-3-hydroperoxynorbornane (4) and endo-2-(anti-1′, 4′-epidioxy-5′,6′-epoxycyclohex-2′-enyl)-exo-2,3-epoxynorbornane (6 and 7) are obtained in addition to 2. Triplet oxygen with 1 gave 2, endo-2-phenyl-exo-2,3-epoxynorbornane (8), and the trimer 9 or 10 of exo-2,3-epidioxy-endo-2-phenylnorbornane. With protic solvents the amount of epoxide increased at the expense of trimer. The singlet and triplet oxygen reactions are discussed in the light of possible intermediates.

Notizen: Flash vacuum thermolysis of dialkylcarbamoyl azides.Thermolysis of several N,N-dialkylcarbamoyl azides 1 in high vacuum gave good yields of 5,5-dialkyl-3-dial-kylamino-2,4-dioxo-5-azonia-imidazolidin-l-id (4) formed by thermal Curtius rearrangements and dimerisation of the resulting N,N-dialkylaminoisocyanates 2.

Notizen: Flash pyrolysis of the 4-arylhydrazono-3-methyl-isoxazol-5-one (1) yields carbon dioxide, acetonitrile, and isocyanoarylamines 2 which under the reaction conditions rearrange to either arylcyanamides 3 or indazoles 4. It is shown by deuterium labelling that only the isocyanoamines not the isomeric nitrile imines are intermediates in the formation of indazoles.

Notizen: Photocyclization of 1, 1′-Polymethylene-di-2-pyridones.Benzophenone sensitized irradiation of the four dipyridones 1-4 gave the internal photocyclization products 6 (64%, Scheme 4), 7 (60%, Scheme 5), 8 (Scheme 6), and 11 (26%, Scheme 7), respectively. The decamethylene compound 5 yielded only polymeric material.The primary [2+2] photoproduct 8 from dipyridone 3 (Scheme 6) is relatively unstable. Further irradiation or heating to 65° induced a Cope rearrangement to give compound 9 which, on heating to 137°, was converted into the isomeric compound 10. This product, as well as the other photoproducts mentioned, are rearranged back to their respective starting materials upon direct irradiation with 254 nm light or by heating to higher temperatures. The various possibilities for cycloadditions of pyridones are discussed as well as the possible factors which are responsible for the highly regioselective photoreactions of the dipyridones 1-4.

Notizen: A detailed study of the reaction of catharanthine N-oxide and vindoline has been carried out employing various conditions. Under optimum conditions, which involve low temperatures and trifluoroacetic anhydride as reagent, 3′, 4′-dehydrovinblastine (XIII, R = COOCH3), in reasonable yields is essentially the exclusive product. However two additional products, 18′ (epi)- 3′, 4′-dehydrovinblastine (XIV, R = COOCH3) and 1′-hydroxy- 3′, 4′-dehydrovinblastine (XVI, R = COOCH3) are also often isolated.The reaction, which follows the course of a Polonovski-type fragmentation process, has been extended to the N-oxide derivatives of dihydrocatharanthine and decarbomethoxycatharanthine to provide again a series of bisindole alkaloid derivatives, also vinblastines. A mechanistic rationale is provided to explain the various results obtained.

Notizen: Determination and configuration of N-glycosyl-3-carbamoylpyridinium ions. A correction.The work reported twenty years ago by one of us (M. V.) [2] has been reproduced and enlarged. In our previous communication we describe how the kinetics of the periodic oxidation of an anomeric pair of nucleosides would allow to assume the configuration and the conformation of the sugar part of the molecule, but our hypothesis was not confirmed by the 1H-NMR. spectroscopy. In the present work we show that our point of view was and is definitively exact, but that N-α- and N-(β-D-glucosyl)-3-carbamoyl-pyridinium-ion have been involuntary confounded in the former publication.

Notizen: Cyclization of diamine 5 with phthalaldehyde and of diamine 6 with glyoxal results in formation of the macrocyclic amino alcohol 8 and the rearrangement product 16, respectively. The properties and stability of 8 and the reactions of 6 with other bifunctional molecules are discussed.

Notizen: Bicyclo[2.1.0]pent-5-yl methyl ketones undergo two thermal isomerization reactions. The endo-exo stereomutation follows the ring-flip path in better than 90%, with inversion of the configuration of the angular carbon atoms by cleavage and reclosure of the central bond. Stereomutation and cyclopropyl-allylic rearrangement to cyclopent-2-enyl methyl ketone do not involve a common intermediate and proceed on separate potential energy surfaces. The activation parameters of the rearrangement suggest an allowed concerted cycloreversion process.

Notizen: Addition-elimination reactions from germanium heterocycles . III. 2,2-Diethyl-2-germa-1,-3-oxazolidines (R = Et; X = O; Y = NH, NMe).The reactions of 2,2-diethyl-2-germa-1,3-oxazolidines with heterocumulenes (PhNCO, PhNCS, CS2, CO2, CH2=C=O) and carbonyl compounds (aldehydes and ketones) are studied. Generally, monoinsertion derivatives are formed by addition of one molecule of the unsaturated compound accross the Ge—N bond. This bond is always the most reactive center of the molecule. In the case of the carbonyl compounds used, diinsertion may occur in a second step by a further addition across a Ge—O bond. Generally, this latter reaction is reversible. By thermal eliminat on of (Et2GeO)n or (Et2GeS)3 the monoaddition derivatives yield the corresponding oxazolidines and thiooxazolidines. The mechanisms of these reactions are discussed.

Notizen: Synthesis of the Macrocyclic Spermidine Alkaloids Oncinotine, Neooncinotine, Isooncinotine and Pseudooncinotine in Racemic Forms.The four isomeric spermidine alkaloids (Scheme 1) mentioned in the title were synthesized as follows: Reaction of the piperidine derivative 5 and the bromide 6 led to the intermediate 13 which was converted to (±)-oncinotine (±-1) and (±)-pseudooncinotine (±-4) (Scheme 3). The analogous reaction of 5 and the isomeric bromid 7 gave the intermediate 22 from which (±)-neooncinotine (±-2) and (±)-isooncinotine (±-3) were synthesized (Scheme 4). The overall yields were found to be between 22 (±-1) and 54% (±-3).

Notizen: A variety of alcohols of the 1-oxycyclopropyl structure, prapared mostly from α-alkoxy-α,β-unsaturated ketnnes and esters by way of reductinn and Simmons-Smith reaction of the resultant α-alkoxyallyl alcohols, are shown to rearrange into cyclobutanones on acid treatment (cf. Scheme 1).

Notizen: Irradiation of pale yellow 5-methyl-1, 4-naphthoquinone (1, Scheme 1) yields the blue photoenol 4-hydroxy-5-methylidene-1(5H)-naphthalenone (2) which is stable at 77 K. At room temperature the enol retautomerizes to starting material, the reaction rate being strongly dependent on the hydrogen-bond-acceptor basicity of the solvent. The enol is trapped in the presence of acid by protonation at the remaining carbonyl oxygen atom and subsequent electrophilic reaction of the exocylclic methylene group.

Notizen: dl-Pumiliotoxin-C (4) was synthesized in a practical manner from trans-4-hexenal (9). The key step 14 → 15 (Scheme 3) involves an intramolecular Diels-Alder reaction giving mainly the cis-fused indanols 15a, which were converted to the cis-fused ketone 16. After Beckmann-rearrangement of 16 the octahydroquinolinone 7 was transformed to the lactim-ether 23. (Scheme 7). Reaction of 23 with propylmagnesium bromide followed by hydrogenation furnished dl-4 in a highly stereoselective fashion.

Notizen: Preparation of the title compounds 11, 12 and 13 is described. Preliminary kinetic results indicate that the hydroxyl substituents in 11 and 12 have a very small retardation effect on the Diels-Alder reactivity of 2,3-dimethylidene-norbornane. The keto group in 13 exerts a larger retardation effect, although it is much smaller than the retardation effect introduced by an exo-5,6-epoxide ring in 2,3-dimethylidene-norbornane.

Notizen: The addition of water, acetic acid, and hydrogen bromide to the strained bridge-head olefins bicyclo[3.3.1]-1(2)-nonene (1), bicyclo[4.2.1]-1(8)-nonene (2), and bicyclo[4.2.1]-1(2)-nonene (3) gives exclusively the bridgehead alcohols, acetates, and bromides, respectively. The reaction rate constants for the addition of acetic acid to the bridgehead olefins 1,2 and 3, and the solvolysis rates for the related 1-bromo-bicyclo[3.3.1]nonane (4) and 1-bromobicyclo[4.2.1]nonane (5) were measured. A comparison of the activation enthalpies of these two reactions gives an estimate of relative strain of the bridgehead double bond. The strain in the bicyclo[4.2.1]nonenes 2 and 3 is similar to that in trans-cyclooctene (8-9 kcal/mol).

Notizen: The cylindrical macrotricyclic ligands 1-3 yield inclusion complexes, [3]-cryptates, with various metal cations. NMR. studies indicate the successive formation of a mononuclear and a binuclear complex. The former is probably unsymmetrical undergoing fast intramolecular cation exchange; the latter is symmetrical, with a cation located on each macrocyclic subunit of the macrotricyclic system. A heteronuclear (Ag2+, Pb2+) complex has been observed. The stability constants of the mononuclear and binuclear alkali and alkaline-earth cation complexes of ligands 1-3 have been determined by potentiometric methods. The stabilities are comparable to those of the complexes of the isolated macrocyclic subunit 5b. The binuclear complexes are almost as stable as the mononuclear one even in highly charged species like for instance the complex of ligand 2 with two barium cations. Cylindrical macrotricyclic ligands are topologically well suited for the designed positioning of two metal cations in a binuclear inclusion complex.

Notizen: Studies on the biosynthesis of muscarine in mycelial cultures of Clitocybe rivulosaThe incorporation and distribution of several 14C-labelled simple compounds into muscarine has been investigated with mycelial cultures of Clitocybe rivulosa. Specifically, the carbon atoms 1, 2 and 3 of pyruvate are incorporated into CH3-C(2), C(2) and C(3), and the carbon atoms 2, 3 and 4 of glutamate into C(4), C(5) and CH2-C(5) of muscarine. The carbon atoms 1 and 5 of glutamate are lost during the biosynthesis. Therefore, muscarine can be regarded as a derivative of glutamate.

Notizen: Synthesis of new polycyclic compounds by means of intramolecular Diels-Alder reactions of cyclohexa-2,4-dien-1-one derivativesThermal rearrangement of mesityl penta-2,4-dienyl ether (1), consisting of the isomers E (93%) and Z (7%), furnished, besides mesitol, the two mesityl penta-1,3-dienyl ethers 2 (24%) and 3 (3%), and the two tricyclic ketones 4 (4,5%) and 5 (12,5%) (Scheme 1). A probable mechanism for this formation of 2 involves a [1,5]-hydrogen shift in (Z)-1. Isomerisation of (E)-1 to (Z)-1 at 145° occurs via reversible sigmatropic [3,3]- and [5,5]-rearrangements of (E)-1 to the cyclohexadienones 38 and 39 respectively (see Chapter A p. 1710, and Scheme 15). Formation of 3 from either (Z)-1 or 2 is rationalized by a series of pericyclic reactions as outlined in Chapter A and Scheme 16.The tricyclic ketones 4 and 5 are undoubtedly formed by internal Diels-Alder reactions of the 6-pentadienyl-cyclohexa-2,4-dien-1-one 6 (Scheme 2). In fact, at 80° 6 is converted into 4 (5%) and 5 (35%). At 80° the cyclohexadienone derivative 7 furnished the corresponding tricyclic ketones 8 (15%) and 9 (44%) (Scheme 2). 5 and 9 contain a homotwistane skeleton. 8 and 9 are easily prepared by reaction of sodium 2,6-dimethylphenolate with 3-methyl-penta-2,4-dienyl bromide at ambient temperature, followed by heating, and finally separation by cristallization and chromatography.The cyclohexadienones 6 and 7 have mainly (E)-configuration. Here too (E) → (Z) isomerization is a prerequisite for the internal Diels-Alder reaction, and this partly takes place intramolecularly through reversible Claisen and Cope rearrangements (Scheme 17). On the other hand, experiments in the presence of 3,5-d2-mesitol have shown (Table 1) that intermolecular reactions, involving radicals and/or ions, are also operating (see Chapter B, p. 1712).Two different modi (I and II) exist for intramolecular Diels-Alder reactions (Scheme 18). Whereas only modus I is observed in the cyclization of 5-alkenyl-cyclohexa-l,3-dienes, in that of (2)-cyclohexadienones 6 and 7 (Scheme 2) both modi are operating. Only in modus 11-type transitions is the butadienyl conjugation of the side chain retained, so that modus 11-type addition is preferred (Chapter C p. 1716).Analogously to the synthesis of the tricyclic ketones 4, 5, 8 and 9, the tricyclic ketone 15 (Scheme 4) and the tetracyclic ketone 11 (Scheme 3) are prepared from mesitol, pentenyl bromide and cycloheptadienyl bromide, respectively.From the polycyclic ketones derivatives such as the alcohols 16, 17, 18, 19, 23, 24 and 25 (Schemes 9 and 11), policyclic ethers 20, 21, 22 and 26 (Scheme 10), epoxides 30, 32 (Scheme 13), diketones 31, 33 (Scheme 13) and ether-alcohols 35 and 36 (Scheme 14) have been prepared. Most of these conversions show high stereoselectivity.

Notizen: Carotenoids in petals of Rosa foetidaThe petals of Rosa foetida, HERRM., a species of prime importance in the history of breeding true yellow garden roses, have been analysed for carotenoids for the first time. The following components were identified: β-carotene (1, 4,5%), lutein (2, 8%), zeaxanthin (3, 17,4%), auroxanthin (4, 30,8%), luteoxanthin (5, 21,9%), violaxanthin (6, 9,2%) and neochrome (7, 4,1%). Not identified carotenoids (4,1%) contained probably mutatoxanthin, antheraxanthin and apocarotenals. Thus the brillant yellow colour of R. foetida flowers is due mainly to carotenoid epoxides.

Notizen: Trimethyl bicyclobutane-1,2,2-tricarboxylate (2) was synthesized by a facile five-step route, beginning with the ferric chloride-catalyzed addition of chloroform to methyl acrylate to give methyl 2,4,4-trichlorobutyrate (3). Replacement of the 2-chloro group by iodide was followed by displacement with dimethyl malonate anion to give trimethyl 4,4-dichlorobutane-1,1,2-tricarboxylate (5a). Thermolysis of the corresponding sodium derivative 5b gave trimethyl cis, trans-3-chlorocyclobutane-1,2,2-tricarboxylate (6). Closure of the bicyclobutane ring to yield 2 was accomplished by potassium hydride in ether with methanol as catalyst.Bicyclobutane 2 polymerized under free radical initiation with breakage only of the 1,3-bond. The homopolymers, obtained in moderate yields, were of low molecular weight, probably owing to steric hindrance effects. Copolymerization occurred with vinyl monomers of varying polarity. The copolymers, obtained in moderate yields, had low molecular weights and consisted mostly of the vinyl comonomer units.

Notizen: The chemical behavior and some physical properties (dipole moment, IR. vs. Raman spectra) of the titled compound are not fully consistent with a strictly centrosymmetric structure which might be expected for the anti configuration. The carbonyl groups are less reactive toward nucleophilic reagents and sp2 → sp3 transformations as compared to cyclopentanone systems.

Notizen: When heated with sodium ethoxide in ethanol 7-methylidenebicyclo[3.3.1]nonan-3-endo-ol (endo-1) is converted into 1-methyl-2-oxa-adamantane (3). This reaction involves nucleophilic addition of a hydroxy group to an unactivated olefinic bond. Formation of the cyclic ether 3 also takes place when endo-1 is heated in aqueous ethanol. This electrophilic addition is strongly catalysed by weak acids and suppressed by weak bases. These unusual reactions proceed more slowly with 7-methylbicyclo[3.3.1]non-6-en-3-endo-ol (endo-2) and can be ascribed to a proximity effect. This follows from the IR. and NMR. spectra of endo-1 and endo-2 which show strong intramolecular hydrogen (OH-π) bonding. The unsaturated endo- and exo-alcohols 1 and 2, respectively, undergo only exo-complexation with silver ion.

Notizen: Synthesis of Bromosubstituted Butenolides II.Methyl 4,4′-dibromosenecioate (2) was prepared by double N-bromosuccinimide bromination of methyl senecioate (1) and converted to methyl 4,4′-diiodo-senecioate (3) with sodium iodide and to 3-bromomethyl-2-buten-4-olide (4) with aqueous hydrobromic acid. A mixture of methyl (Z)- and (E)-4-bromosenecioate (8 and 9) yielded 3-methyl-2-butenolide (5) with aqueous hydrobromic acid and a mixture of (Z)-and (E)-4-methoxy-senecioic acid (10 and 11) with methanolic potassium hydroxide. N-Bromosuccinimide treatment of the butenolide 5 afforded 4-bromo-3-methyl-2-buten-4-olide (6) and 4,4-dibromo-3-methyl-2-buten-4-olide (7).

Notizen: Preparation of 2,3-Dimethyl-5,6-dihydro-4H-1,2-oxaziniumiodide was achieved by N-alkylation of 3-methyl-5,6-dihydro-4H-1,2-oxazine. Reactions with C-nucleophiles led to the corresponding N-methyl-perhydro-1,2-oxazine derivatives. Reaction with sodium hydride in triglyme led to 3-methyl-4-aza-1,3-pentadiene.

Notizen: Synthesis and absolute configuration of chiral 2, 3, 10, 11-tetrahydroxy-8-methylberbines [3].The synthesis and absolute configuration of the four optically active berbines Xa, b and XIa, b are described. These compounds consitute potential ‘alkaloids’ obtained by condensation of either R-(+) or S-(-)-norlaudanosoline (THP, III) with acetaldehyde, a major metabolite of ethanol.

Notizen: γ-Lactone-cis-annulation to Δ2- and Δ3- Cholestene.From Δ2- and Δ3- cholestene the γ-lactones 11a, 11b, 12a, and 12b are synthesized through the dibromocarbene adducts 3 and 4, the bromohydrines 5 and 6, the oxapiropentanes 7 and 8, and the cyclobutanones 9a, 9b and 10a, 10b, respectively. The 13C-NMR.-spectra of 1-8 and 11 as well as the ORD.-spectra of the cyclobutanones 9 and 10 are reported.

Notizen: Synthesis of human insulin. III. Preparation of the A(14-21) - B(17-30) fragment.In the recently published total synthesis of human insulin [1], one of the three principal intermediates is the protected fragment in which sequence 14-21 of the A chain is linked to sequence 17-30 of the B chain by the disulfide bridge between A 20 and B 19. The synthesis of this fragment, and its characterization are described in detail in the present report.This open-chain asymmetrical cystine peptide was prepared by elongating the two chains in the already published intermediate first with fragment A(14-19), Bpoc-Tyr(But)-Gln-Leu-Glu(OBut)-Asn-Tyr(But)-NH-NH2 (azide coupling), and secondly with fragment B(21-30), H-Glu(OBut)-Arg-Gly-Phe-Phe-Tyr(But)-Thr(But)-Pro-Lys(Boc)-Thr(But)-OBut (DCCI/HOBt).

Notizen: Sensitized irradiation (λ = 254 nm) of the title compounds 2 a and 2 b in benzene affords the tetracyclic oxetanes 3 a and 3 b. The irradiation of 2 c under similar conditions yields equal amounts of 3 c and the cyclopentadiene derivative 5. The formation of the photoproducts is discussed.

Notizen: The hydroxyazo-quinonehydrazone equilibrium of the cyclic triazonaphthalene 1 has been determined from the 1H-NMR. spectrum of the 15N-labelled compound. The size of the coupling constant J15N, H demonstrates that the equilibrium of 1 with respect to the non-cyclic reference compound 6 is shifted towards the hydroxyazo form by factors of at least 5.1 and 3.9 in DMSO and H2O, respectively.

Notizen: 2-Thia-7-aza-isotwistanes.The access to the 2-thia-7-aza-isotwistane system was achieved by water addition to the twistene 1 yielding the isotwistanol 2, characterized also as its acetate 4. Analogous D2O/D2SO4-treatment of the twistene 1 (→ 3) allowed to deduce the reaction pathway for the formation of 2. The chloride 6, obtained from 2, on treatment with lithium aluminium hydride gave a mixture of unsubstituted isotwistane 8 and twistane 9, whereas silver acetate treatment of 6 led to the isotwistyl acetate 4 and possibly only to traces of the corresponding twistyl acetate 7.

Notizen: Isolation and identification of evernine in ‘Oakmosse’ (Evernia prunastri (L.) Ach.).A new depside, evernin (1), has been found in the lichen Evernia Prunastri (L.) Ach. The determination of the structure and the spectral parameters of 1, especially the 13C-NMR. spectrum, are described.

Notizen: A novel course of a phenylation reaction of 1,5-dihydroxy-4,8-diaminoanthraquin-one-2,6-disulfonic acid with cresols.The arylation of 1,5-dihydroxy-4,8-diaminoanthraquinone-2,6-disulfonic acid with m-cresol in conc. sulfuric acid gives in the presence of boric acid a mixture of monosulfonic acids which differ in the substitution of the m-cresol moiety. The main product (8, 95%) is substituted at the p-position to the methyl group, the side product (12, 5%) at the p-position to the OH group. The monosulfonic acid 8, which could not be isolated is further sulfonated under the reaction conditions to the disulfonic acid 9. In the case of o-cresol, the cresol moiety is substituted in the p-position (16) to OH group and in the case of p-cresol in the o-position (20) to OH group. The obtained monosulfonic acids 16 and 20 resp. are partially sulfonated further under the reaction conditions. The new structures are elucidated by 1H- and 13C-NMR. spectroscopy and the pattern of arylation reaction with phenol is discussed.

Notizen: Localization of the keto group in Inandenin-ones.By Schmidt degradation of the spermidine alkaloids inandenine-12-on (1) and inandenine-13-on (2) from Oncinotis inandensis followed by hydrolysis, acetylation and esterification four different types of products were obtained: the dicarboxylic diesters 9 and 10, the ω-amino-carboxylic esters 11 and 12, the acetylated polyamines 14 and 15, and the acetylated triaminecarboxylic esters 16 and 17. By GLC. and mass spectral analysis of these degradation products, and by comparison with synthetic compounds it was possible to confirm the structures 1 and 2. The same alkaloid mixture (1+2) was obtained from the leaves of Oncinotis nitida BENTH.

Notizen: Synthese of sulfonated derivatives of 2-amino-p-xyleneSulfonation of 2-amino-p-xylene (2) gave 2-amino-p-xylene-5-sulfonic acid (1). The 2-amino-p-xylene-6-sulfonic acid (3) was prepared via three routes: (1) sulfonation of 2-amino-5-chloro-p-xylene (19) to 5-amino-2-chloro-p-xylene-3-sulfonic acid (20) followed by hydrogenolysis; (2) sulfur dioxide treatment of the diazonium salt derived from 2-amino-6-nitro-p-xylene (21) to 2-nitro-p-xylene-6-sulfonyl chloride (11) followed by hydrolysis to 2-nitro-p-xylene-6-sulfonic acid (4) and Béchamp reduction; (3) Béchamp reduction of 2-chloro-3-nitro-p-xylene-5-sulfonic acid (13) to 3-amino-2-chloro-p-xylene-5-sulfonic acid (16) and subsequent hydrogenolysis. Catalytic reduction of 13 in aqueous sodium carbonate solution gave mixtures of 3 and 16. 2-Amino-p-xylene-3-sulfonic acid (27) was synthesized via two routes: (1) reaction of 19 with sulfamic acid to 2-amino-5-chloro-p-xylene-3-sulfonic acid (26) followed by hydrogenolysis; (2) sulfur dioxide treatment of the diazonium salt derived from 2-amino-3-nitro-p-xylene (28) to 2-nitro-p-xylene-3-sulfonyl chloride (12), hydrolysis to 2-nitro-p-xylene-3-sulfonic acid (7) and Béchamp reduction.

Notizen: Total synthesis of human insulin. IV. Description of the final steps.Recently a preliminary account was given of a new synthetic pathway leading to human insulin. In the present report the last steps of this synthesis - i.e. as from the unsymmetrical cystine derivative I - are described in detail. I contains the sequences A(14-21) and B(17-30), linked by the disulfide bridge A20-B19. These last steps are: (1) selective removal by pH-controlled acidolysis in trifluoroethanol of N(α)-Trt from leucine B17, (2) completion of the B-chain by coupling with the fragment B(1-16), (3) selective removal by trifluoroethanol of N(α)-Bpoc at tyrosine A14, (4) completion of the A-chain by coupling with the cyclic fragment A(1-13), (5) removal of the acid labile protecting groups, and (6) formation of the disulfide bond A7-B7 from the two S-acetamido-protected cysteine residues by treatment with iodine.As judged by the composition of the reaction mixture the closure of the 85-membered ring proceeds with a cyclization yield of over 70%. From the last step in the synthesis two products were obtained after extensive purification by counter-current distribution: pure human insulin in a yield of 50% and its [D-tyrosine B16]Isomer in a yield of 25%. Although the partial racemization of tyrosine B16 occurred during coupling with sequence B(1-16), the [D-tyrosine B 16]-stereoisomer could only be separated at the endproduct stage.The available evidence indicates that the ease of formation of the disulfide bond A7-B7 does not depend on the precursor molecule already having an insulin-like conformation.

Notizen: A simple synthesis of a series of bicyclo[m.n.0]-1-alkenes (m, n = 3,4,5) from 2-oxocycloalkanecarboxylates by the intramolecular Wittig reaction is reported (see p. 70-72). The spectral properties (IR., 1H-NMR. and 13C-NMR.) of these annulated trisubstituted olefins are discussed.

Notizen: Synthesis of substituted 2-amino-3-hydroxy-pyridines by nucleophilic displacement of a halogene in halopyridines2-Amino-3,5-dihalogeno-pyridines (halogene: chlorine and/or bromine) react with bases in aqueous-alcoholic or in aprotic polar solvents to the corresponding 2-amino-3-hydroxy-5-halogeno-pyridines. In higher alcohols as solvents pyridyl-alkylethers are formed which then undergo ether-cleavage. As a by-product a mono-dehalogenated compound, 2-amino-5-halogeno-pyridine, is formed, but no 2-amino-3-halogeno-pyridine is dependent on the nature of the leaving group at position 3, on the base, and on the solvent. Copper or its salts accelerate the formation of pyridin-3-ols as well as the dehalogenation of the pyridines at position 3.No evidence has been found for the formation of a 3,4-pyridine by dehydrohalogenation of the halopyridines or for the formation of 2-amino-3-halogeno-5-hydroxy-pyridines by the ANRORC-mechanism. Hence it is assumed that the above mentioned reactions proceed via a radical-anion mechanism.

Notizen: Aromatic Sigmatropic Hydrogen-Shifts in 2-Vinyl- and 2-Allyl-phenolsIt is shown by deuterium labeling experiments that 2-vinylphenols, on heating at 142,5°, undergo aromatic [1,5]-H-shifts whereby o-quinone methides are formed as intermediates (Scheme 7). Thus, heating of 2-isopropenylphenol (6) in a D2O/dioxane mixture leads to a rapid deuterium incorporation into the methylidene group of the isopropenyl moiety (Table 1) whereas its methyl group shows only a slow uptake of deuterium. The latter exchange process can be attributed to intermolecular reactions (Scheme 8). The quinone methide intermediates (e.g. 26, Scheme 8) can be regarded as vinyl homologues of alkyl ketones. Therefore, 26 can exchange hydrogen in both methyl groups by an acid- and base-catalysed mechanism. Indeed, when 6 is heated in D2O/pyridine or D2O/CH3COOD/dioxane, an almost statistical incorporation of deuterium into the methylidene and the methyl group of the isopropenyl moiety is observed (Table 3).As a consequence of thermally induced [1,5]-H-shifts, 2-(1′-propenyl)-phenols undergo rapid (E,Z) isomerization with first order kinetics on heating above 140° in decane solution. Activation parameters are given in Table 4. The observed primary +++++ H/D isotope effect of 3.3 in the (E,Z) isomerization of phenol 8 is in +++ment with intramolecular H/D-shifts in the rate determing step (Scheme 9 +++ Table 5). As expected aromatic sigmatropic [1,5]-H-shifts in 2-(1′-propenyl)-+++ are much faster than aromatic homosigmatropic [1,5]-H-shifts in 2-(2′-+++++)phenols (Scheme 1 and Table 6). The structurally comparable phenols +++ (Z)-10 and (E)/(Z)-14 (Scheme 3) show k([1,5])/k(homo-[1,5]) ≈ 2300 at ++++A more detailed discussion in English is given in [1]. .

Notizen: The triacetate of the antibiotic lysolipin (1) crystallizes in the space group P21, a = 11.059, b = 21.453, c = 8.423 Å, β = 109.76°. X-ray analysis was used to determine the structure of this compound.

Notizen: (-)-Pumiliotoxin-C-hydrochloride, as well as its unnatural enantiomer, have been synthesized in an enantioselective manner starting from (S)- or (R)-norvaline, respectively. In the crucial cycloaddition step 11 → 12 (cf. scheme 2) the chiral center of 11 controls to a major extent the three developing centers of chirality. This synthesis shows unambigously the (2S)-configuration of natural pumiliotoxin-C.

Notizen: On the Formation of Polycyclic Ketones in the Reaction of 5, 6-Dimethylidene-bicyclo[2.2.1]hept-2-ene with Diiron-enneacarbonyl5,6-Dimethylidene-bicyclo[2.2.1]hept-2-ene (4), in the presence of diiron-ennea-carbonyl in boiling hexane, produces the endo-and exo-tricarbonyl-iron complex of 4 (endo- and exo-5). A mixture of numerous tricarbonyl-iron complexes with ligands derived from coupling and carbonylation reactions of 4 are also formed. The endo- and exo-5 compounds as well as two tricarbonyl-iron complexes (7 and 8) of penta-cyclic ketones could be isolated and characterized. After oxidative removal of the tricarbonyl-iron groups in the reaction mixture the three pentacyclic ketones 9, 10 and 11 were separated. Structure and configuration of these ketones were deduced from spectroscopic analyses, especially from their 1H- and 13C-NMR. spectra (see tables 1-4). Whereas the symmetric pentacyclic ketone 11 is of a known type (cf. [1]) the two spiroketone 9 and 10 represent compounds of a new type. Their structure and configuration shows that in ironcarbonyl induced thermal cyclopentanone formations, an exocyclic double bond can also take part.

Notizen: Synthesis of two phenolic amino acids containing the 1,2,4-oxadiazole ringThe synthesis of α-amino-β [3-(p-hydroxyphenyl)-1,2,4, oxadiazol-5-yl]propionic acid (9) and its β-amino isomer (10) (see scheme 3) is reported. By condensation of p-benzyloxy-benzamide oxime and N-benzyloxycarbonyl asparagine the derivatives 4 and 5 (see scheme 1) are obtained leading after deprotection to 9 and 10. The synthesis of N-carboxyanhydride of 4 (6) and its corresponding amino acid (7) and amide (8) is also described.

Notizen: The kinetics of the base catalysed racemization of [Co(EN3A)H2O]Abbreviations: EN3A3-=(-OOCCH2)2N(CH2)2NHCH2COO-; ME3A3-=(-OOCCH2)2N(CH2)2 N(CH3)CH2COO-; EDDA2-=-OOCCH2NH(CH2)2NHCH2COO-; EDTA4-=(-OOCCH2)2N(CH2)2N(CH2COO-)2;TNTA4-=(-OOCCH2)2N(CH2)3N(CH3COO-)2; HETA3-=(-OOCCH2)2N(CH2)2N(CH2COO-)CH2CH2OH; en=H2N(CH2)2NH2; Meen=H2N(CH2)2NHCH3; sar-=-OOCCH2NHCH3. were studied polarimetrically in aqueous buffer solution. The reaction rate is first order in OH- and in complex, in weakly acidic medium. Activation parameters are ΔH≠=22 kcal · mol-1, ΔS≠=26 cal · K-1. The results are discussed in terms of an SN1CB mechanism involving exchange of the ligand water molecule.The N-methylated analogue [Co(ME3A)H2O] does not racemize in the pH-range investigated. Loss of optical activity occurs at a rate which is about 1,000 times slower than the racemization of [Co(EN3A)H2O](60°) and coincides with the decomposition of the complex.

Notizen: A Note on Exchange of a Cyanogroup for a Dialkylaminogroup in Cyclobutene-1,2-dicarbonitrile and (E)-EthylenedinitrileReactions of electrophilic cyclobutene-1,2-dicarbonitrile and (E)-ethylene-dinitrile with secondary amines lead to 1:1 adducts of type 3 and 12, respectively. These adducts eliminate hydrocyanic acid either thermally or, more conveniently for preparative purposes, upon treatment with a strong base (e.g. t-butoxide or methoxide) affording 2-dialkylaminocyclobutenes-1-carbonitriles 4 and 3-dialkylamino-acrylnitriles 13, resp., in high yields.

Notizen: The racemic spirosesquiterpenes β-acorenol (1), β-acoradiene (2), acorenone-B (3) and acorenone (4) (Scheme 2) have been synthesized in a simple, flexible and highly stereoselective manner from the ester 5. The key step (Schemes 3 and 4), an intramolecular thermal ene reaction of the 1,6-diene 6, proceeded with 100% endo-selectivity to give the separable and interconvertible epimers 7a and 7b. Transformation of the ‘trans’-ester 7a to (±)-1 and (±)-2 via the enone 9 (Scheme 5) involved either a thermal retro-ene reaction 10 → 12 or, alternatively, an acid-catalysed elimination 11 → 13 + 14 followed by conversion to the 2-propanols 16 and 17 and their reduction with sodium in ammonia into 1 which was then dehydrated to 2. The conversion of the ‘cis’-ester 7b to either 3 (Scheme 6) or 4 (Scheme 7) was accomplished by transforming firstly the carbethoxy group to an isopropyl group via 7b → 18 → 19 → 20, oxidation of 20 to 21, then alkylative 1,2-enone transposition 21 → 22 → 23 → 3. By regioselective hydroboration and oxidation, the same precursor 20 gave a single ketone 25 which was subjected to the regioselective sulfenylation-alkylation-desulfenylation sequence 25 → 26 → 27 → 4.

Notizen: The racemic cis-anti-trans-steroids 9 to 11 have been synthesized in a highly stereoselective manner starting from 4-methoxybenzocyclobutene carboxylic acid via the key step 8 → 9. (cf. Scheme 2).

Notizen: The constitution and absolute configuration of the rhoeadine alkaloids (+)-alpinigenine and (+)-cis-alpinigenine.The fundamental structure of the hemi-acetal phenylbenzazepine alkaloid (+)-alpinigenine (1), isolated from Papaver bracteatum LINDL., was derived essentially from 1H-NMR.- and mass-spectra of 1 and its derivatives 7, 10 and 14 (cf. Scheme 2). The positioning of the four methoxy groups in the two aromatic rings could be deduced from the 1H-NMR.-spectra of the N-oxides 14 and 15 in which, as a result of favourable sterical and conformational behaviour, an interaction exists between the N-oxide oxygen atom and one of the two ortho protons in ring C.The B/D-trans-fused 1 undergoes isomerization in 1N HCl to cis-alpinigenine (16). A stereochemical correlation between bases in the trans-and cis-series was enabled via an Emde degradation of the corresponding methylacetal-methyliodides 21 resp. 19 leading to the enantiomeric isochroman derivatives 22 resp. 23 which are achiral at C (2) (Scheme 4).The configuration at C (14) in the hemi-acetals (eg. 1 and 16) and the methyl ethers (eg. 7 and 8) is discussed in detail (cf. Scheme 7). (+)-Alpinigenine (1) has the (1S, 2R, 14R) configuration and (+)-cis-alpinigenine (16), in chloroform or acetone solution, the (1R, 2R, 14R) configuration.

Notizen: The mass spectral retro Diels-Alder-reaction: 1,2,3,4-tetrahydrocarbazole1,2,3,4-Tetrahydrocarbazole undergoes a retro Diels-Alder-reaction under electron impact. C(2) and C(3) are eliminated as ethylene. This is shown by measuring the deuterated derivatives 1a, 1b and 1c. Furthermore the oxo-1,2,3,4-tetrahydrocarbazole derivatives 3 and 4 are investigated in respect to the mass spectral retro Diels-Alder reaction too.

Notizen: Electrolytic oxidation of 4,5,7,8-tetramethyl[2.2]paracyclophane (I) yields a paramagnetic species which by ESR. spectroscopic evidence must be ascribed to the dimeric radical cation I2 · ⊕. Analogous dimers are obtained from the 12, 13, 15, 16-tetradeuterio- and 1, 1, 10, 10, 12, 13, 15, 16-octadeuterio-derivatives of I so that all coupling constants can be unequivocally assigned to sets of equivalent protons. The hyperfine data for I2 · ⊕ are consistent with an effective D2h or D2d symmetry, the four benzene rings lying in parallel planes.

Notizen: The vapour pressure of CuCl2 and the dimerization of CuCl2(g) have been investigated by optical spectroscopy in the range 420-650°C, pCl2 = 0.5-5 atm.The enthalpy of dimerization of CuCl2(g) was determined by visible and by Raman spectroscopy and good agreement was found (-154 kJmol-1 and -143 kJmol-1). CuCl2(g) shows two totally symmetric Raman modes (373 and 127 cm-1) indicating that, at least at elevated temperatures, CuCl2(g) is not a linear molecule. The optical spectra of Cu2Cl4(g) and CuLCl5(g) (L = Ga, In) are very similar supporting a CuCl3-chromophor in both cases.The formerly proposed structure of CuL2Cl8(g) (L = Al, Ga) contains bridging and terminal chlorides, structural elements also present in Cu2Cl4(g). In agreement with the proposed structure vCu-Clterm is identical in Cu2Cl4(g) and CuL2Cl8(g), while VCu-Clbridg. is at lower energies (20-30 cm-1) in CuL2Cl8(g) than in Cu2Cl4(g).

Notizen: On the Stereochemistry of the Aromatic Claisen Rearrangement. Thermal Rearrangement of erythroid and threoid ortho-Dienones.Erythro- and threo-1-methyl-1-(1′-methyl-2′-propynyl)-2-oxo-1,2-dihydronaph-thalene (erythro- and threo-6) as well as erythro- and threo-2,6-dimethyl-6-(1′-methyl-2′-propynyl)-cyclohexa-2,4-dien-1-one (erythro- and threo-8) were obtained together with the corresponding aromatic ethers 5 and 7 by alkylation of 1-methyl-2-naphthol and 2,6-dimethyl-phenol, respectively in alcoholic potassium hydroxide solution with 1-methyl-2-propynyl p-toluenesulfonate (Scheme 2). The diastereoisomeric dienones 6 and 8 were easily separated by column chromatography on silica gel and its relative configuration at C(1) or C(6) and C(1′) deduced from the chemical shifts in their 1H-NMR.-spectra (Table 1). Hydrogenation of 6 and 8 using Lindlar catalyst yielded the corresponding erythro- and threo-configurated (1′-methyl-2′-propenyl)-dienones 10 and 13, respectively (Scheme 3) the thermal rearrangement of which were studied. The following results were obtained: threo-10 rearranged in benzene at 85-105° preferentially via a chair-like (C) transition state to yield 99,5% (E)- and 0,5% (Z)-(2′-butenyl) 1-methyl-2-naphthyl ether ((E)- and (Z)-14; ΔΔG105,7°≠ (C/B) = -4,0 kcal/mol). On the other hand, erythro-10 when heated at 105-125° in benzene gave 84,7% (E)- and 15,3% (Z)-14, i.e. in this case a boat-like (B) transition state is favoured (G105,7°≠ (C/B) = + 1,3 kcal/mol) (Scheme 5 and Table 2). The thermal rearrangement of dienones 13 led to the corresponding ethers 12 as well as p-allyl-phenols 11. Thus, heating of threo-13 at 20-42° in cyclohexane resulted in the formation of 2,5% of ether 12, consisting of 98% of the (E)- and 2% of the (Z)-isomer, and 97,5% of (E)-11 which contained, at a maximum, 0,5% of the (Z)-isomer, (Scheme 6 and Table 3). This means that both rearrangements occurred with a strong preference of the C transition state (G41,6°≠ (C/B, phenol) = -3,3 kcal/mol). On the contrary, erythro-13 when heated at 42-68° in cyclohexane yielded a 3:2 mixture of ether 12 and phenol 11 (Scheme 6). The ethereal part consisted of 88,0% of the (E)- and 12,0% of the (Z)-isomer which again shows that the B geometry predominated in the erythro transition state leading to the ether (G42,7°≠ (C/B)= + 1,3 kcal/mol). In the phenolic part 36-40% of the (E)-isomer and 64-60% of (Z)-isomer were found which means that in the para-Claisen rearrangement of erythro-13 the C arrangement is only slightly favoured (ΔΔG42,7°≠ (C/B)= -0,36 kcal/mol).

Notizen: Synthesis and Reactions of 8-membered Heterocycles from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Saccharin or Phthalimide3-Dimethylamino-2,2-dimethyl-2H-azirine (1) reacts at 0-20° with the NH-acidic compounds saccharin (2) and phthalimide (8) to give the 8-membered heterocycles 3-dimethylamino-4,4-dimethyl-5,6-dihydro-4 H-1,2,5-benzothiadiazocin-6-one-1,1-dioxide (3a) and 4-dimethylamino-3,3-dimethyl-1,2,3,6-tetrahydro-2,5-benzodiazocin-1,6-dione (9), respectively. The structure of 3a has been established by X-ray (chap. 2). A possible mechanism for the formation of 3a and 9 is given in Schemes 1 and 4.Reduction of 3a with sodium borohydride yields the 2-sulfamoylbenzamide derivative 4 (Scheme 2); in methanolic solution 3a undergoes a rearrangement to give the methyl 2-sulfamoyl-benzoate 5. The mechanism for this reaction as suggested in Scheme 2 involves a ring contraction/ring opening sequence. Again a ring contraction is postulated to explain the formation of the 4H-imidazole derivative 7 during thermolysis of 3a at 180° (Scheme 3).The 2,5-benzodiazocine derivative 9 rearranges in alcoholic solvents to 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl) benzoates (10, 11), in water to the corresponding benzoic acid 12, and in alcoholic solutions containing dimethylamine or pyrrolidine to the benzamides 13 and 14, respectively (Scheme 5). The reaction with amines takes place only in very polar solvents like alcohols or formamide, but not in acetonitrile. Possible mechanisms of these rearrangements are given in Scheme 5.Sodium borohydride reduction of 9 in 2-propanol yields 2-(5′-dimethylamino-4′,4′-dimethyl-4′H-imidazol-2′-yl)benzyl alcohol (15, Scheme 6) which is easily converted to the O-acetate 16. Hydrolysis of 15 with 3N HCl at 50° leads to an imidazolinone derivative 17a or 17b, whereas hydrolysis with 1N NaOH yields a mixture of phthalide (18) and 2-hydroxymethyl-benzoic acid (19, Scheme 6). The zwitterionic compound 20 (Scheme 7) results from the hydrolysis of the phthalimide-adduct 9 or the esters 11 and 12. Interestingly, compound 9 is thermally converted to the amide 13 and N-(1′-carbamoyl-1′-methylethyl)phthalimide (21, Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2-amino-isobutyric acid. However, the reaction mechanism is not clear at this stage.

Notizen: 13C- and 195Pt-NMR. spectra for the complexes trans-PtCl2(amine)(CH2=CH2) have been measured. For amine = (S)-N-methyl-α-methylbenzylamine the two diastereomers present may be distinguished from the values 3J(Pt,C). The 195Pt-chemical shift is shown to be sensitive to subtle differences stemming from intramolecular non-bonded interactions.

Notizen: Synthesis and IR. Spectroscopic Identification of Epimeric 3-Ethinyl-5α-cholestan-3-olsThe syntheses of the 3β-ethinyl-5α-cholestan-3α-ols 2a, 2b, 2c and of the corresponding epimeric 3α-ethinyl-5 α-cholestan-3 β-ols 3a, 3b, 3c are described. Bands at 1000 cm-1 for the α-alcohols and at 1030 cm-1 for the β-alcohols are found to be useful for the IR. spectroscopic identification of epimeric 3-ethinyl-5α-cholestan-3-ols.

Notizen: The isodynamical interconversion between the quasiplanar equilibrium conformers 1b and 1c of 1,5-bisdehydro[12]annulene requires a free energy of activation ΔG# = 4.5 ± 0.2 kcal/mol (120 K) which was determined by line shape analysis of its temperature-dependent NMR. spectrum. Force field calculations indicate that this barrier reflects the energy needed to disrupt the cyclic π-conjugation in going to the nonplanar transition state 1a.

Notizen: The synthesis of two new polyamines containing 2-pyridyl and 6-methyl-(2-pyridyl) groups is described. The equilibria between H+ and Co2+ and the new ligand 1,9-di(2-pyridyl)-2,5,8-triazanonane (dptn) as well as the protonation of the hydroxo complexes of 1,6-di(2-pyridyl)-2,5-diazahexane-Co(II) (Co(dpdh) and 1-(6-methyl-2-pyridyl-6-(2-pyridyl)-2,5-diazahexane-Co(II) (Co(mdpdh)) have been studied in aqueous solution using the pH method. The coordination ability of the pyridine containing ligand dptn is compared with the chelating tendency of the analogous aliphatic amine (tetren). In spite of the lower basicity of the pyridine derivative the stability constants of its Co(II) complex is higher by a factor of thirty. The absorption spectra give evidence for a pseudooctahedral geometry of Co(dpdh) (H2O)2+2 and Co(dpdh)(H2O)(OH)+. Oxygen-uptake measurements indicate the formation of binuclear peroxo species. The potentiometric equilibrium data indicate the presence of dibridged species (dpdh)Co(O2, OH)Co(dpdh)3+ and (mdpdh)Co(O2, OH)Co-(mdpdh)3+. The kinetics of the rapid O2-uptake was measured over a wide pH range on a stopped-flow apparatus. For Co(dpdh)2+ and Co(mdpdh)2+ we found a second order rate constant independent of pH up to pH 9, but in more alkaline solutions it increases and reaches an upper limit around pH 12.3. The data could be fitted by a rate law of the form k1 = (k′1[H+] + k″1 KH) ([H+] + KH)-1. This variation with pH was explained by a rapid equilibrium Co(dpdh) (H2O)2+2 ⇌ Co(dpdh)(H2O)(OH)+ + H+(KH). The enhanced rate constants of the hydroxo species must arise from a rate determining H2O replacement by O2, dominated by Co-OH2 bond breaking and the expected ability of an OH- group to labilize neighboring H2O molecules. The protonation constant of the hydroxo complex obtained by equilibrium measurements (pKH = 11.19 ± 0.03) was in good agreement with that derived from kinetic data (11.12 ± 0.04). The hydrolysis of Co(dptn)(H2O)2+ influences the rate of O2-incorporation in a different way. In this system retardation occurs as a result of hydrolysis ascribed to the slower leaving of OH- compared to H2O. This was expected if a mechanism with rate determining H2O replacements by O2 holds.

Notizen: The ionisation energies and the HeI photoelectron spectra of the N-oxides of diazabenzenes are presented. The valence electronic structures of the N-oxides are discussed in view of the ionisation energies, and the profiles, of the bands. The interpreted data are compared to calculations which are in good agreement. The results are correlated to the physicochemical studies, and particularly to the electronic absorption spectroscopy, of the N-oxides. The assignment of the photoelectron spectra of the azabenzenes are considered with reference to the spectra of their N-oxides.

Notizen: The synthesis and characterization of (±)-coralydine and (±)-O-methylcorytenchirine and their optical isomers are described.

Notizen: Distribution and Metabolism of Octadec-9-ynoic acid in RatsOctadec-9-ynoic acid (stearolic acid) fed to rats leads to the metabolic excretion of six dicarboxylic acids with retained triple bond. The main metabolic steps are ω-, β-, and presumably α-oxidation. Feeding of 14C-stearolic acid proves that the α-oxidative steps involves the methyl end of the original acid. It could further be shown that this acid is incorporated partially in the body lipids. To a substantial degree it is totally oxidized and expired as 14C—CO2.

Notizen: S-Methylation of 6-S-benzyl-6-deoxy-1,2-O-isopropylidene-3-O-methyl-α-D-xylo-6-thiohexofuranos-5-ulose (1) gave the expected sulfonium salt 2 which on alcaline treatment yielded the stable sulfur ylide 3. This compound constitutes an useful synthetic intermediate in carbohydrate chemistry. On heating in 1,2-dimethoxyethane, it underwent a Stevens rearrangement which led to an extension of the carbon chain of the sugar and, reacted with Michael acceptors, it gave cyclopropanation reactions.

Notizen: Acid-catalyzed rearrangement of 7-hydroxyroyleanone into a 20(10→9) abeo-abietane derivative and two phenalenonesShort treatment of either horminone (1b), taxoquinone (1a), 6,7-dehydroroyleanone (3) or 6β-hydroxyroyleanone (1c) with 80% H2SO4 at 0° leads to a mixture of rearranged products. Two of the structures, determined by X-ray-cristallography, were found to be (9R, 10R)-20(10→9)-abeo-12-hydroxy-5,7, 12-abietatriene-11,14-dione (4) and 9-isopropyl-2,2,5-trimethyl-8H-phenaleno[1,9-bc]furan-8-one (5), and the third compound, isolated in very small amounts, has been provisionally identified as 3-hydroxy-9-isopropyl-2,2,5-trimethyl-8H-phenaleno[1,9-bc]furan-8-one (6) from the spectroscopic data.

Notizen: Intramolecular cyloadditions of binaphtyl compoundsThree new bridged ketones, 7,8 and 9, have been isolated in 44%, 3% and 19% yields respectively (Scheme 2) by heating 2,2′-bis-allyloxy-1,1′-binaphthyl (5) at 215° for 16 hours. These compounds could be epimerized about C(16) by bases, and in particular 9 yielded the new epimer 10. The structures of the alcohols obtained by reduction of the keto group are also given (Scheme 2). The constitution of all compounds was derived from spectroscopic data, chiefly from their 1H-NMR, spectra (tab. 2, 3 and fig. 1). The assignments were based on the observed long-range coupling constant between H(endo)-C(16) and H(endo)-C(5) in 7 and 10 and on the analysis of chemical shifts and coupling constants in both the ketones and their derivatives. Moreover, the structures of the compounds investigated have been proved by x-ray analysis of ketone 8 (chap. 3, fig. 2). The thermal conversion of binaphthylether 5 to the bridged ketones proceeds via an intramolecular Diels-Alder reaction, followed by Claisen rearrangement (Scheme 8). On heating, the bis-beta-methylallyl ether 20 yielded the ketone 21 and a small amount of the ether 23 (Schemes 5 and 7). Ether 23 and binaphthyl monoallyl ether 26 were converted thermally to the bridged ketones 31 (Scheme 7) and 27 (Scheme 6) respectively. In addition, 26 underwent an intramolecular ene-reaction to give the spiroketone 28 (Schemes 6 and 9). The structures of these compounds were also established, mainly by analysis of their 1H-NMR. spectra.

Notizen: N-Isobutyl-11-(3, 4-methylenedioxyphenyl)-undeca-2,4,6-trans, trans, trans-trienoic amide (II) and N-isobutyl-11-(3,4-methylenedioxyphenyl)-undeca-2,8,10-trans, trans, trans-trienoic amide (III), two of the three possible structures of the alkaloid piperstachine, have been synthesized. Compound (III) has been found to be identical with piperstachine. The 1H- and 13C-NMR. spectra of the compound (II) are discussed.

Notizen: Synthesis and Absolute Confifguration of the Enantiomers of Verapamil.Starting from the acids IV-(+) and IV-(-), a synthesis of the enantiomers I-(+) and I-(-) of the coronary vasodilator Verapamil is described and their absolute configuration determined through a chemical filiation with the acid XII-(S)-(+).

Notizen: The He I photoelectron spectra of tetramethylcyclopentane-1,2,3-trione 1, 4,4,6,6-tetramethylcyclohexane-1,2,3-trione 2, bicyclo[1.2.3]octane-2,3,4-trione 3, bicyclo[2.2.3]nonane-2,3,4-trione 4 and anhydrous ninhydrine 5 are presented. The assignment of the first two bands is discussed using semiempirical calculations together with a qualitative band shape analysis. It is shown that the first two bands in 1 to 4 are due to the ionization of an electron from lone pair combinations of the 2p-oxygen orbitals.

Notizen: The mass spectra of the three cyclopentane-1,2,3-triols, six cyclopentane-tetrols and four cyclopentane-pentols stereoisomers have been studied. Complex processes, especially regarding the H2O eliminations, were detected by extensive deuterium labelling.

Notizen: Phenylpropionamides acylated in the ortho position with aralkanecarboxylic acids were cyclised to give, after reduction, 1-aralkyl-tetrahydro-2-benzazepines.

Notizen: The higher homologues of n-alkanes H(CH2)NH with N 〉 ∽ 13 yield photoelectron spectra in which the C2s-bands merge to form a double humped, unresolved C2s-band system in the interval of I=15 to 25 eV [1]. It is shown that with the help of an equivalent bond orbital model one can derive a closed formula, which gives the individual C2s-band positions Ijm=-εj in function of N and j with sufficient accuracy, assuming the validity of Koopmans' approximation. The calculated Ijm values (j=1 to N) folded with an appropriate shape function for the individual C2s-bands reproduce the observed Franck-Condon envelope of the C2s-band system within narrow limits of error. However, a comparison of the observed total width of the C2s-band system with the computed one, indicate that for large n-alkanes (N≥ ∽ 13), the simplification which consists of taking into account only the interaction matrix elements between vicinal bond orbitals [2], is no longer a satisfactory one.

Notizen: It is shown that the ab initio STO-3G treatment applied to simple saturated linear, branched and cyclic hydrocarbons, assuming standard geometries, yields orbital energies ∊jSTO-3G for their canonical orbital ϕj which correlate perfectly with the observed C2s ionization energies Ijm, if Koopmans' approximation is accepted.Applying the Foster-Boys localization procedure to these canonical orbitals ϕj leads to localized orbitals λμ and their corresponding Hartree-Fock matrix Fλ = (Fλ,μv). An examination of the matrix elements Fλ,μv, i.e. of the self-energies Aμ = Fλ,μμ of the localized CC- and CH-orbitals λμ and of the cross terms Fλ, μv (μ ≠ v) between them, leads to the conclusion that a satisfactory approximation should be obtained by setting Aμ = A for all μ, Fλ,μv = B if λμ and λv are vicinal and neglecting all other cross terms. The resulting model is nothing but the well-known equivalent bond orbital model of Lennard-Jones & Hall, which however can now be calibrated using the known C2s-ionization energies of hydrocarbons. Due to the discrete structure and the wider range (∽ 8 eV) of the C2s band systems in the photoelectron spectra of these molecules this leads to a more satisfactory parametrization than using the narrower and badly resolved C2p band system.Comparison of calculated band positions using the calibrated model with observed C2s-band ionization energies for a series of hydrocarbons reveals that the simple equivalent bond orbital model is better than one might have expected.

Notizen: Starting from ethyl 2-cyclohexen-1-carboxylate (3) the total synthesis of the perhydrohistrionicotoxin intermediate 23 was achieved in 25% overall-yield. The two key steps involve a positionally specific addition of HOBr to the oxime-olefin 7 and the alkylation of bromooxime 17 with 1-lithio-1-butyne. The latter represents a novel method for stereospecific and position-specific introduction of a nucleophilic butyl equivalent in α-position to a ketonic carbonyl group.

Notizen: Experiments on the competitive incorporation of farnesol-stereoisomers into cantharidinFarnesol (2) has been demonstrated to be an efficient precursor for cantharidin (1), into which it is transformed by elimination of C(1), C(5), C(6), C(7) and C(7′) [1]. The following incorporation experiments with doubly labelled (3H and 14C) stereoisomers of farnesol present strong evidence that (E,E)- farnesol ((E,E)-2) in fact is the precursor for cantharidin, whereas (2E, 6Z)-2 and (Z,Z)-2 are not utilized for the biosynthesis of cantharidin. A possible mechanism for the incorporation of (2Z,6E)-farnesol ((2Z,6E)-2) to an extent of 56,8% relative to (E,E)-2 is discussed.

Notizen: The crystal structure of 6-methyl-7,8-dihydropterine-monohydrochloride-monohydrateThe crystal structure of the title compound has been determined by X-ray analysis (direct methods) and refined with 990 structure amplitudes to R = 0.025. The crystal system is triclinic, space group P1, with unit cell dimensions a = 5.859, b = 7.686, c = 12.107, α = 71.84, β = 76.35, γ = 85.80. The molecule is protonated at the N(5)-position and is planar. The atoms H(19) and H(20) are with 0.818 Å above respectively with -0.705 Å under the plane.

Notizen: Structure of a Stable Dipolar Compound from 2,2-Dimethyl-3-dimethylamino-2H-azirine and Benzoylisothiocyanate.Benzoylisothiocyanate and 2,2-dimethyl-3-dimethylamino-2H-azirine (1) react to given the dipolar compound 4,4-dimethyl-2-thiazolin-5-dimethylimminium-2-benzcarboxamidate (2), whose structure has been proved by X-ray analysis. Compound 2, upon addition of water, yields the thiourea derivative 3, whereas by acid catalyzed hydrolysis the thiazolinone derivative 4 is formed. The dipolar structure 2 is also existent in organic solvents like dimethylsulfoxide or chloroform.

Notizen: One the Reactivity of π-(η5-)-Cyclopentadienylpalladium-δ-(η1-)-allyl- and π-(η5-)-Cyclopentadienylpalladiumhalide Complexes; New ortho-Metallation Reactions of Trio-o-tolylphosphitTeil des Hauptvortrages von H. W. an der Jahrestagung der Chemical Society, York (U.K.), 7.-11.4.1975. 20.Mitt. der Reihe «Untersuchungen zur Reaktivität von Metall-π-Komplexen»; 19.Mitteilung siehe [1].(η5-C5H5)Pd(η3-2-ClC3H4) reacts with Lewis bases L[PPh3, P(OPh)3, P(O-p-Tol)3, P(O-o-Tol)3, CO] in a 1:1 molar ratio to give the η1-2-chloroallyl complexes 2a-2e. (η5-C5H5)-Pd(η1-2-ClC3H4)P(O-o-Tol)3 (2d) which is stable at room temperature has been isolated as a red oil. It represents the first well-characterized η1-allylpalladium derivative.2a-2d eliminate allene to form (η5-C5H5)PdClL (5a-5d). The tri-o-tolylphosphite complex 5d reacts with NaI to give (η5-C5H5)PdIP(O-o-Tol)3 (6) and on Al2O3 to give (η5-C5H5)Pd[P(OC6H3-o-Me)(OC6H4-o-Me)2] (7). Elimination of HCl leading to ortho-metallation of one of the six-membered rings of tri-o-tolylphosphite also occurs in the reaction of PdCl42- and P(O-o-Tol)3 to form Pd2Cl2[P(OC6H3-o-Me)(OC6 H4-o-Me)2]2 (9). This reacts with TlC5H5 to give 7. The preparation of Pd2Cl4[P(O-o-Tol)3]2 (8) and Pd2I2[P(OC6H3-o-Me)(OC6H4-o-Me)2]2 (10) is also reported.

Notizen: On Reactions of oxygenated Cobalt(II) Complexes. V. Reactivity of diastereoisomeric μ-peroxo-μ-hydroxo-dicobalt(III) IonsThe kinetics of dissociation of μ-peroxo-μ-hydroxo-dicobalt(III) chelates have been reinvestigated using a stopped flow technique. The binuclear cations [(trien)Co(O2, OH) Co(trien)]3+, [(tren)Co(O2, OH)Co(tren)]3+ and [(en)2Co(O2, OH)Co(en)2]3+ dissociate on acidifying to Co2+ and the protonated ligand and up to 100% of the bound O2 is evolved. The dissociation is H+-catalyzed and first order in complex. The observed rate constants at pH 2 are in the range of 10-3 to 10-1 s-1 (20°). They depend not only on the nature of the ligand and on ligand configuration but also on the diastereoisomeric structure of the binuclear cation.In the case of trien there are 8 possible chemically different isomers. On oxygenation of Co(trien)2+ in dilute solution 3 of those isomers seem to be formed preferentially. Their rate constants are separated over a factor of 50. For [(en)2 Co(O2, OH)Co(en)2]3+ there exist a meso form and a chiral structure. On oxygenation of Co(en)22+ in dilute solution the meso form and the racemate are formed to about equal amounts. The racemate dissociates about 5 times slower. Of the 3 possible achiral isomers of [(tren)Co(O2, OH)Co(tren)]3+ one is formed stereoselectively by oxygenation in solution.

Notizen: The 1H-decoupled 13C-NMR. spectra of 35 all-trans, 17 mono-cis vitamin A compounds (acetates, alcohols, aldehydes, acids and esters) and of one 11, 13-di-cis compound (11, 13-di-cis retinol) are reported. Included in this investigation are desmethyl-, desmethylethyl, and aryl-vitamin A analogues and others as well as 30 reference compounds of smaller molecular weight. Furthermore, the 13C-NMR. spectra of 23 β-apo- and other carotenoids were studied. A complete assignment of the signals of all 106 compounds to the specific carbon atoms was achieved by extensive application of lanthanide shift reagents, mainly Yb(dpm)3, by CW-offset and selective 1H-decoupling experiments, by comparison of the shifts of related compounds, and in three cases by utilization of specifically deuteriated compounds (11, 12-D2-retinol and retinyl acetate, 15, 15′-D2-β-carotene). The chemical shift differences between the cis- and trans-vitamin A compounds and the applicability of the shift reagents for the assignment of the 13C-NMR. spectra are discussed.

Notizen: Enol derivatives in the chlorophyll series. 132-Desmethoxycarbonyl-173-desoxy-132,173-cyclochlorophyllide a-enol and a method for the introduction of magnesium into porphinoid ligands under mild conditionsMagnesium transfer from the iodo-magnesium salt of 3,5-di-t-butyl-4-hydroxy-toluene (BHT) into methyl pheophorbide a is a fast process in methylenechloride/ether solution at ambient temperature. This procedure for the introduction of magnesium into labile chlorin ligands has made possible the preparation of a crystalline 132, 173-cyclochlorophyllide a-enol. Concomitant use of the lithium salt of BHT facilitates the more critical insertion of magnesium into methyl bacteriopheophorbide a. The preparative success of these magnesium transfers depends crucially upon the solvent system used. Under conditions where the complexation of methyl pheophorbide a with iodo-magnesium-BHT is essentially complete within 2 minutes at 12° in methylenechloride/ether solution, strong inhibition of the magnesium transfer is observed by cosolvents such as pyridine, dimethylacetamide, dioxan or tetrahydrofuran.

Notizen: Application of Ring Expansions for the Preparation of rac-Muscone and Exaltone®4,6-Undecamethylene-2-pyrone (8), prepared from 1-morpholino-cyclododec-1-ene (7) according to Hünig et al., was saponified and decarboxylated to a mixture of the 3-methyl-cyclotetradecenones 11, 12, 13 and 14, which was hydrogenated to 3-methyl-cyclotetradecanone (3). Similarly, 4,6-dodecamethylene-2-pyrone (16) was prepared from 1-morpholino-cyclotridec-1-ene (15) and ketene, saponified to a mixture of the 3-methyl-cyclopentadecenones 19, 20, 21 and 22 and the latter hydrogenated to rac-muscone (6).The ratios of the four regio- and stereoisomers in the above mentioned two mixtures of 3-methyl-cycloalkenones were derived from the 1H-NMR.-spectra.From the reactions of the enamines 7 and 15 were also isolated small amounts of 4,5-decamethylene- (9) and 4,5-undecamethylene-6-methyl-2-pyrone (17) respectively. Saponification and partial decarboxylation of 9 lead to (2-acetyl-cyclododec-1-enyl)-acetic acid (23) and methyl-(2-methyl-cyclododec-1-enyl)-ketone (24), the latter possessing an incense-like odor.The keton homologation method of Mock & Hartman (reaction of alkanones with diazoacetic ester in the presence of triethyl oxonium fluoroborate, followed by saponification and decarboxylation) was applied three times in succession, starting with cyclododecanone (1). This furnished, after the first stage, the cyclotridecanone (4) required for the above described synthesis of rac-muscone (6) and, after the third stage, cyclopentadecanone (5 = exaltone®).Application of this reaction to 2-methyl-cyclododecanone (28) resulted in a low yield of 2-methyl- (30) and 3-methyl-cyclotridecanone (31) in the ratio of 2:1.

Notizen: Neue Cephalosporine, die in 3-Stellung eine Fluormethylgruppe aufweisen (9, 17/Schema 1), wurden ausgehend von 2b unter Verwendung von 2-Chlor-1,1,2-trifluor-triäthylamin als Fluorierungsmittel hergestellt. Mit Piperidin-schwefeltrifluorid erhielt man ferner aus 18 die 3-Difluormethyl-cephemverbindung 19 (Schema 2), die nach bekannten Methoden in antibakteriell wirksame Cephalosporine (20a, b) übergeführt wurde. 3-Fluor-cephemderivate, z.B. 23b, liessen sich ausgehend von entsprechenden 3-Hydroxy-cephemverbindungen, mit diesem Reagens jedoch nur in sehr geringer Ausbeute herstellen.

Notizen: The Rǒle of Paliclavine in the Biosynthesis of Ergot AlkaloidsFeeding of [N-14CH3]-paliclavine to submersed cultures of Claviceps paspali Stevens et Hall and to surface cultures of the ergot fungus from Pennisetum typhoideum Rich. has shown that paliclavine is not involved in the biosynthesis of either the ergolene carboxylic acids or the tri- and tetra-cyclic clavines.

Notizen: The structure elucidation of C-β-glucuronides of sulfinpyrazone (Anturan®) and phenylbutazone (Butazolidin®) by spectroscopic means is reported. These conjugates represent a novel type of drug metabolites.

Notizen: Nous avons synthétisé une série de spiropyrannes benzoxathioliques par un processus en deux étapes: obtention de perchlorates styryliques en milieu acide par condensation simultanée de trois substrats intermédiaires, puis cyclisation en milieu basique. Un mécanisme est proposé.Ces spiropyrannes benzoxathioliques sont photochromes et nous avons étudié la cinétique de décoloration thermique ainsi que l'absorption visible de leurs photomérocyanines. Des observations comparables à celles enregistrées en série benzodithiolique nous ont amenés ici encore à envisager une structure de type quinonique pour la mérocyanine.

Notizen: Tetrammine-copper(II)-tetraiodide Cu(NH3)4I4 crystallizes in the monoclinic space group C 2/m. The crystal structure has been determined from X-ray diffractometer data and refined to Rw = 2.2%. Four coplanar nitrogen atoms and two axial iodine atoms form an octahedral coordination around Cu(II) with a pronounced 4 + 2 tetragonal distortion. A connection of the Cu(II) atoms by linear, centrosymmetric I42- polyiodide ions results in infinite chains of [Cu(NH3)42+ I42-]-units. The central I-I-bond distance in I42- is 2.802(1) Å; a considerable amount of I-I bonding is indicated by the distance of 3.342(1) Å found for the terminal bonds. These intramolecular bond distances correspond to calculated I-I-bond orders of 0.80 and 0.43.

Notizen: Synthese und Eigenschaften von 3,7-Dehydrotroponen7-exo-Brom-7-endo-t-butyl-(9) und 7-exo-Chlor-7-endo-phenyl-bicyclo[3.2.0]hept-2-en-6-on(12) sowie 7,7-Dichlor-2,3-benzo-bicyclo[3.2.0]hept-2-en-6-on (16), das letztere hergestellt aus Dichlorketen und Inden (15), wurden mit 1 Moläquiv. N-Bromsuccinimid behandelt. Die entsprechenden Hauptprodukte waren 4-exo-, 7-exo-Dibrom-7-endo-t-butyl-(10) und 4-exo-Brom-7-exo-chlor-7-endo-phenyl-bicyclo[3.2.0]hept-2-en-6-on (13) sowie 4-exo-Brom-7, 7-dichlor-2, 3-benzo-bicyclo[3.2.0] hept2-en-6-on (17). Neben dieser « normalen » Bromierung fand in zwei Fällen eine solche unter Allylisomerisierung statt: Als Nebenprodukt bei der Monobromierung von 12 wurde 4-exo-Brom-6-exo-chlor-6-endo-phenyl-bicyclo[3.2.0]hept-2-en-7-on (14) gebildet und bei der Dibromierung von 9 (wahrscheinlich via 10) war das Hauptprodukt 2,4-exo, 6-exo-Tribrom-6-endo-t-butyl-bicyclo[3.2.0]hept-2-en-7-on (11).Aus der Behandlung der vier bromierten Bicycloheptenon-Derivate 10, 11 und 13 sowie 17 mit 1,1 mol Triäthylamin bei tiefer Temperatur liessen sich 2-t-Butyl-(5), 6-Brom-2-t-butyl-(6) und 2-Phenyl-3, 7-dehydrotropon(7) sowie 2-Chlor-4, 5-benzo-3, 7-dehydro-tropon (8) isolieren.Das Reaktionsverhalten und die spektralen Eigenschaften (1H-NMR., 13C-NMR., IR. und UV.) der Dehydrotropone 5, 6, 7 und 8, sowie ihr Zusammenhang mit deren Struktur werden detailliert beschrieben.

Notizen: Photochemistry of α,β-epoxy-eucarvone.On π,π*-excitation (λ = 254 nm) 4 isomerizes to the bicyclic ketoaldehyde 5; on n,π*-excitation (λ ≥ 280 nm) 4 gives 5, the β,γ-unsaturated ketone 6, the enone 7 and the cyclobutanone 8. Scission of the (C - C)-bond of the oxirane 4 would give the dihydrofurane e, which could isomerize to the ketoaldehyde 5. On the other hand, 4 is assumed to isomerize to the β,γ-unsaturated aldehyde c, which could yield 6 and 7 by photodecarbonylation. The cyclo-butanone 8 is shown to be a photoisomer of the ketone 6.Furthermore, eucarvol (18) rearranges by a thermal [1,5]-H-shift to dihydro-eucarvone (20); on UV.-irradiation 18 gives the bicyclic isomers 27 and 28.

Notizen: The formation of isomeric esters in the title reaction takes place through different mechanisms; one of them does not imply formation of isomerized substrate.

Notizen: The crystal structure of 12,13-dibromopseurotin has been determined by single crystal X-ray analysis. The crystals belong to space group P21 with a = 16.75, b = 9.63, c = 7.42 Å, β 95.9°, Z = 2. The structure was solved by the heavy atom technique and refined to R = 0.062 with 819 significant reflexions for 299 parameters.

Notizen: Transformation of the Tricyclo[5,4,0,03,9]undecadiene System into the new Octahydro-2,5-methano-azulene System.1,3,6-Trimethyl-tricyclo[5.4.0.03,9]undeca-5, 10-dien-2-one (1) was successively treated with sodium amide in toluene, potassium hydroxide in water, LiAlH4 in ether and TsCl in pyridine to give the p-toluenesulfonate 5 in 66% overall yield. The solvolysis of 5 resulted in the remarkably clean formation of 6, 8a-dimethyl-9-methyl-iden-2,5-methano-1,2,3,3a,4,5,8,8a-octahydroazulene (6). The carboxylic acid 3 upon treatment with thionylchlorid in benzene at 70° underwent a spontaneous intramolecular Friedel-Crafts acylation to give 9 and 10 which have the same carbonskeleton as 6. The endo-chloro configuration of 10 was demonstrated by reduction of 10 to 4; this reaction proceeds presumably through a reductive fragmentation, the stereoelectronic requirements of which are given in the endo-isomer of 10 only.

Notizen: Determination of Bjerrum Formation Curves by Differential Vapour Pressure Osmometry.A differential vapour pressure osmometry method for the determination of Bjerrum formation curves is described. This technique allows the determination of formation constants in nonaqueous solvent systems.

Notizen: The reaction of 4-chloro-2-phenylquinazoline with K15NN2 has been studied by 15N-NMR. spectroscopy. 15N-chemical shifts in 5-phenyl-1 (3)-[15N]-tetrazolo[1,5-c]quinazoline and -Nα(Nγ)-[15N]-4-azido-2-phenylquinazoline are reported. The characteristic IR. absorption frequencies of the tetrazole group have been determined in a series of annelated 15N-labelled compounds. From these studies and the chemistry of the labelled tetrazoles, it is concluded that all haloazines examined react with KN3 by the direct nucleophilic substitution mechanism. An addition of nucleophile-ring opening-ring closure (ANRORC) mechanism was not observed. The synthesis of several 15N-labelled tetrazoloazines is described.

Notizen: Peptide synthesis: The following of the cleavage of benzyl protecting groups with 1H-NMR. spectroscopy.In spite of the great number of signals 1H-NMR. spectroscopy can be used to demonstrate the presence or absence of oxygen bound benzyl groups in protected viz. deprotected peptides.

Notizen: Photolysis of Bicyclo[3.3.1]nonan-2-one.Disproportionations to the unsaturated aldehydes 2 and 3 or the ketene 4, the secondary processes available to the acyl-alkyl biradical b[X(9) = CH2] formed from bicyclo[3.3.1]nonan-2-one (1) in a primary photochemical process by α-cleavage (Norrish type I cleavage), were studied.If the acyl-alkyl biradical b [X(9) = CH2] has a lifetime sufficient to permit rotation around one or several bonds before H-transfer occurs, considerations about the energetically most favored conformations of b allow to deduce the following preference for intramolecular H-abstraction: at C(9) (f → unsaturated aldehyde 2) 〉 at C(3) (1 → ketene 4) 〉 at C(8) (i → unsaturated aldehyde 3). If H-transfer takes place very quickly, following an energetically favored small conformational change of the acyl-alkyl biradical, one expects H-abstraction at C(9) and/or C(3) to be preferred over that at C(8). These predictions were fully confirmed by the experiments.UV. irradiation of bicyclo[3.3.1]nonan-2-one (1) in n-pentane gave a complex mixture of the unsaturated aldehyde 2 and products of further photochemical reactions of 2:43 and 44, 45 and 46, 49-52, and 54-57 (see below). Photolysis of 1 in methanol, however, yielded 82% of 2 and 1,2% of ester 23, the final product from ketene 4 formed by trapping of a solvent molecule.UV. irradiation of the 9,9-dideuterio-ketone 20 confirmed the intramolecular D-abstraction at C(9) (→ unsaturated aldehyde 21) and consequently the H-abstraction at C(9) in the sequence 1 → 2. That either of the two H-atoms at C(9) in 1 can be abstracted was demonstrated by the photolysis of the C(9)-epimeric 9-acetoxy-bicyclo[3.3.1]nonan-2-ones 24 and 25 in methanol. In both cases the unsaturated aldehyde 26 was formed, which corresponds to abstraction of H - C(9)c(7) and H - C(9)C(3)15, respectively.In separate UV. irradiation experiments it was shown that the products accompanying the unsaturated aldehyde 2 (photolysis of 1 in n-pentane) were formed in the following ways: diene 43 and acetaldehyde (44) from 2 by intramolecular γ-H abstraction followed by Norrish type II reaction; the spiro-alcohols 45 and 46 from 2 by intramolecular γ-H abstraction followed by ring closure to cyclobutanols; the oxetanes 49-52 by cycloaddition (Paterno-Büchi reaction) of acetaldehyde (44) to 3-methylidene-cyclohexene (43); the aliphatic alcohols 54-57 by addition of acetaldehyde (44) to n-pentane, i.e. H-abstraction from the hydrocarbon solvent followed by combination of the radicals thereby formed.