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Notes: Zur Oxydation von Thebain mit m-Chlorperbenzoesäure, IIIDie Oxydation von Thebain (1) mit m-Chlorperbenzoesäure ist stark abhängig von den gewählten Reaktionsbedingungen. In unserem Fall wird neben 14-Hydroxy-codeinon (2) auch das bekannte, mono-acetylierte Diol 3 erhalten. Die Rückführung von 3 in 2 und die Verknüpfung mit dem bekannten Ketodiol 5, über das bisher nicht beschriebene 8, 14-Dihydroxydihydrothebain (4) wird gezeigt.

Notes: Debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines 1, 6, 7 with hydrochloric acid and ethanol gave the corresponding phenolic isoquinolines 2, 8, 9 and tetrahydroprotoberberines 4, 12, 13. Compounds 2, 8, 9 on photolysis also gave, besides the expected noraporphines 3, 10, 11, the tetrahydroprotoberberines 4, 12, 13 [1-4] (Schemes 1 and 2). 6-Benzyloxy-1-(5-benzyloxy-2-bromo-benzyl)-1,2,3,4-tetrahydroisoquinoline (27a) containing no methoxy or methylenedioxy groups either in ring A or C does not give protoberberine during debenzylation; but 28, the debenzylation product of 27a, on photolysis gives both the noraporphine 29 and the tetrahydroprotoberberine 30 (Scheme 6), proving that during debenzylation of 1-(3-benzyloxybenzyl)-1,2,3,4-tetrahydroisoquinolines containing additional methoxy or methylenedioxy groups, the necessary formaldehyde comes from the latter groups. During photolysis both the methoxy groups (methylenedioxy groups) and the C(3) atom of the tetrahydroisoquinoline moiety provide the formaldehyde. Veratrole under debenzylation and photolytic conditions and tetrahydroisoquinoline under the latter condition also give rise to formaldehyde (Schemes 8 and 10).The novel bromohomoprotoberberine 43 along with 42 was formed during debenzylation of the 1-phenethyl-1,2,3,4-tetrahydroisoquinoline 41. Photolysis of 42 yielded the novel nor-homoaporphine 44, in addition to 43; the latter was debrominated to give the homoberbine 45.

Notes: Metabolism of Acetylenic Monocarboxylic and Dicarboxylic AcidsFeeding of acetylenic monoacids with chain length of 11 to 18 C-atoms to rats led to excretion of dicarboxylic acids with retained triple bonds. 10-Octadecynoic acid led to the formation of metabolites with even and odd number of C-atoms, suggesting in addition to established ω- and β-oxidation an α-oxidative pathway.

Notes: The Carbo(3-phenylpyrazol-5-yl-hydrazonoyl) halides 1a,b react with active methylene compounds to yield the 1-(3-phenylpyrazol-5-yl)-pyrazole derivatives 2a-k (Scheme 1). The acyclic intermediates 3a,b could be isolated from reaction of 1a,b with acetylacetone, thus establishing the substitution mechanism for these reactions.Compounds 1a, b reacted with carbon disulfide, phenyl isothiocyanate, methyl cyanide, and with p-chlorobenzaldehyde to yield the corresponding heterocyclic derivatives 5-8, respectively (Scheme 2).The behaviour of compounds 2 with hydrazine hydrate is reported.

Notes: Apart from the well-known constituents (+)-β-selinene (2), (-)-β-elemene (4), (+)-β-costol (7), (-)-caryophyllene (17), and (-)-elemol (19) the following sesquiterpenoids have been isolated for the first time from costus root oil (Saussurea lappa CLARKE): (-)-α-selinene (1), (+)-selina-4, 11-diene (3), (-)-α-trans-bergamotene (5), (-)-α-costol (6), (+)-γ-costol (8), (-)-elema-1,3,11 (13)-trien-12-ol (9), (-)-α-costal (11), (+)-γ-costal (12), (+)-γ-costal (13), (-)-elema-1,3,11 (13)-trien-12-al (elemenal, 14), (-)-(E)-trans-bergamota-2, 12-dien-14-al (15), (-)-ar-curcumene (16), and (-)-caryophyllene oxide (18). Compounds 6, 8, 9, and 13 are new sesquiterpenoids. IR. and NMR. spectra of 12 sesquiterpenoids are reproduced.

Notes: (E)-9-Isopropyl-6-methyl-5,9-decadien-2-one (1a), a terpenoid C14-ketone with a novel skeleton, was isolated from costus root oil (Saussurea lappa CLARKE) and its structure established by a two-step synthesis from thuja ketone (2). The possible role of the new compound as an intermediate in the biosynthesis of the irones is discussed.

Notes: Membrane Selectivity and Syntheses of Ionophores for Li+. Stability Constants in EthanolElectrically neutral, lipophilic complexing agents were prepared which induce Li+ selectivity in solvent polymeric membranes. Stability constants for group IA and IIA cations of one such ligand in ethanol have been determined. The selectivity behaviour of this ligand in membranes as well as in extraction systems is studied and discussed in terms of model considerations.

Notes: Preparation of heterocyclic substituted stilbenyl derivatives of 2H-1,2,3-triazoleSchiff's bases derived from 2- and 4-(p-formylphenyl)-2H-1,2,3-triazoles and o- or p-chloroaniline are reacted with various p-tolyl substitued aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding heterocyclic substituted stilbenes (“Anilsynthesis”). In order to avoid opening of the 2H-1,2,3-triazole ring, the reaction is carried out without external heating. In many cases an improvement in yield is obtained by irradiation with UV. light at the beginning of the reaction.

Notes: The 2-trimethylsilylethyl residue, a selectively cleavable carboxyl protecting groupIn a search for new carboxyl protecting groups suitable for use in peptide synthesis, 2-trimethylsilylethyl esters [-COOCH2CH2Si(CH3)3] of several N-protected amino acids have been prepared. These esters can be synthesized in good yields from Na-benzyloxycarbonyl-amino acids and 2-trimethylsilylethanol with dicyclohexylcarbodiimide in the presence of pyridine. They are stable under a wide variety of conditions used during coupling and work-up in peptide synthesis. For removal the 2-trimethylsilylethyl group is readily cleaved by fluoride ions, preverably using a quaternary ammonium fluoride in dimethylformamide. Some side reactions which occurred during the removal of the 2-trimethylsilylethyl group are discussed.Special attention has been paid to the question of racemization during the treatment with fluoride ions. No. evidence of racemization was found in any of the cases examined.

Notes: Charge Transfer Compounds of Metal Complexes. I. Bis(o-phenylenediamido)-Nickel Complexes as DonorsThe synthesis of monosubstituted bis(o-phenylenediamido)-nickel complexes NiL2=Ni(C6H3(NH)2R)2 where R = H, OCH3, Cl, sec-butyl, and of the disubstituted complex Ni(C6H2(NH)2 (CH3)2)2 is described. Substitution has a strong influence on the polarographically investigated reduction/oxidation behaviour of the complexes. Reaction of the nickel complexes with strong electron acceptors A (A = chloranil, tetracyanoethylene, 2,3-dichloro-5,6-dicyano-p-benzoquinone, 7,7,8,8-tetracyanoquinodimethane) yields solid compounds with a stoichiometric composition NiL2: A = 1:1. IR. And UV./VIS. Spectroscopic data indicate an ionic ground state of the solids. Electrical conductivities of solids are in the range 4,3·10-3 ω-1 cm-1 to 5·10-12 ω-1 cm-1 at 298 K with activation energies of 0.33 eV to 1.68 eV.In some cases solution equilibria in acetone or dichloromethane have also been investigated. The general scheme is: The tight ion pair NiL2+A- gives no ESR.-signal. Low temperatures or addition of R4NClO4 salts favour the formation of the ionic species.

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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]. .

Notes: 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.

Notes: (-)-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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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).

Notes: 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).

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: 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.

Notes: Identification of farnesol as an intermediate in the biosynthesis of cantharidin from mevalonolactoneSimultaneous injection of 2-[14C]-mevalonolactone (2-[14C]-1) and (E,E)-11′,12-[3H]-farnesol (11′,12-[3H]-2) into Lytta vesicatoria L. (Coleoptera, Meloidae) yields doubly labelled cantharidin (3). The remainder of the precursor farnesol, re-isolated from the insects after the incubation period, has incorporated 14C-radioactivity. The labelling pattern in this farnesol, as determined by two independent degradative reaction sequences, is in agreement with the isoprene rule. Since specific incorporation of farnesol (2) into cantharidin (3), and of mevalonolactone (1) into both, farnesol (2) and cantharidin (3) is observed, the sesquiterpene alcohol 2 acts as an intermediate in the biosynthesis of the C10-compound 3 (Scheme 1).

Notes: Some pentaamine complexes of Co(III) with 2,6-bis(aminomethyl)pyridine (bamp), a diamine ligand (or two ammonia ligands) and one unidentate ligand have been prepared (Table 1). In all these species, bamp remains coordinated meridionally under a variety of conditions as shown by 1H- and 13C-NMR. spectroscopy and correlations by stereoretentive reaction cycles. The rates of amine proton exchange and of spontaneous aquation, Hg2+-induced aquation and base hydrolysis of some chloropentaamine complexes have been determined. They essentially follow the patterns observed for complexes with purely aliphatic amine ligands; the presence of a pyridine donor in these complexes does not suggest deviations from the mechanistic schemes usually proposed for the solvolytic reactions investigated.

Notes: 4a-(Z-1-Propenyl)-bicyclo[4.4.0]dec-1(8a)-en-2-one (6) and 4a-(Z-1-propenyl)-bicyclo[4.4.0]deca-1(8a), 7-dien-2-one (17) undergo an intramolecular hydrogen transfer from the methyl group of the propenyl substitutent to the α-carbon atom of the enone group, and cyclization to the [4.4.3]propellane derivatives 9 and 30, respectively, when excited in the π → π* wavelength region. The quantum yield for (Z)-6 → 9 under optimum conditions is 0.29 at 254 nm. These reactions occur specifically from the S2 (π,π*) state, competing with the S2 → T decay. The triplet reactions of 6 are E-Z double-bond isomerization, double-bond shift to (E,Z)-8, and rearrangement to (E)-10. Further investigations concern some structural limitations in the scope of the reaction type 6 → 9 and enone S2 reactivity in general.

Notes: Regiospecific reduction of 1,3,3-trisubstituted succinimides by diboraneIt is possible to reduce 1,3,3-trisubstituted succinimides regiospecifically by diborane at the less substituted carbonyl group to yield the corresponding lactams. This method was used specially for the reduction of 2,8-diazaspiro[4,5]decane-1,3-diones to 2,8-diazaspiro[4,5]decan-1-ones. These results are in contrast to those of Speckamp et al. [4a-h] in which sodiumborohydride/HCl was the reducing agent. Possible explanations for the selective reductions are discussed, using the principles of steric approach control of Dunitz & Bürgi [6] and of Baldwin [8].

Notes: Cyclization reactions with 2-(β-styryl)benzylamines 5-Phenyl-1H-2-benzazepinesCyclization of the urea derivative 3 with POCl3 to give 2-(4-methyl-1-piperazinyl)-4-phenylquinoline (4) was carried out in analogy to the quinoline synthesis of Foulds & Robinson. This reaction was used for the preparation of 2-benzazepines. The trisubstituted ureas 6 and 8, derived from the 2-(β-styryl)-benzylamines 5, were cyclized with POCl3 to yield the 3-amino-5-phenyl-1H-2-benzazepines 7 and 9, respectively. Similarly, cyclization of the corresponding acetyl-derivatives 10 gave the 3-methyl-5-phenyl-1H-2-benzazepines 12. On the other hand, the disubstituted urea 15, cyclized under the same conditions to the 1-methyl-1-phenylisoindoline derivative 16, and 2-(β-styryl)benzylamine (5a) on treatment with phosgene gave the isoindoline 17 in an analogous manner.

Notes: Structure of the adduct from 3-dimethylamino-2,2-dimethyl-2H-azirine and 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate3-Dimethylamino-2,2-dimethyl-2H-azirine (1) reacts with 3-methyl-2,4-diphenyl-1,3-oxazolium-5-olate (5a) to give a 1:1 adduct (7) in a 88% yield. Its crystal structure has been determined by X-ray analysis (direct methods) and refined with 1056 structure amplitudes to R = 0,032. The crystal system is monoclinic, space group P21/c, with unit cell dimensions a = 10.663, b = 9,828, c = 18,592 Å, and β = 90,63°. It is obvious that 4-dimethylamino-5,5-dimethyl-2-[α-(N-methyl-benzamido)benzyliden]-Δ3-1,3-oxazoline (7) arises from an addition of 1 to the valence-polaromeric ketene form 5b of the mesoionic oxazolone 5a (Scheme 3).

Notes: Contribution to the study of the behaviour of catechin in alkaline mediumWhen catechin (1) is warmed with aqueous alkali it first undergoes rapid epimerisation. After some time a novel bridged carbocyclic enol, catechinic acid (3) separates out and may be isolated in excellent yield. Eventually catechinic acid isomerises to 2-(3′,4′-dihydroxyphenyl)-3,9-epoxy-6-oxo-bicyclo[3,3,1]-non-7-en-8,9-diol (4) via an open chain anion (5) which is also involved in the epimerisation of catechin. Assignments of structure are given and the equilibria observed are discussed.

Notes: Reaction of monosubstituted epoxypropanes with benzylamineThe reaction of the epoxides of the general formula with benzylamine at 40, 50 and 60°C has been examined. The determination of rate constants by variation of X has shown, that in the case of X = S or N no anchimeric acceleration occurred. These results have been approved by product analysis and by synthesis of the possible reaction products. Transition states of the epoxide/benzyl-amine reaction are discussed by means of the experimentally determined activation energy and activation entropy.

Notes: Die kristalline und molekulare Struktur von 4-Aza-5-oxo-tricyclo[4.4.0.03,8]decan (Aza-twistanon)Die kristalline Struktur von Aza-twistanon wurde durch eine Röntgenstruktur-analyse untersucht. Die Kristalle gehören zur monoklinen Raumgruppe P21/n mit den Zelldimensionen a = 6,662(6), b = 13,36(2), c = 8,606(9) Å, β = 98,97(2)°, V = 757 Å3, Z = 4. Die Struktur wurde mit Direktmethoden gelöst und bis zu R = 0,035 verfeinert (mittlere σ(c) = 0,003 Å3).Die cis-Amidgruppe ist relativ stark deformiert und hat einen Torsionswinkel Cα-C′-N-Cα von 14,5(4)° (Deformation aus der Ebene χc = 5,0(5)° und χN = 13,5(4,0)°). Die gegenüberliegende äthylenbrücke weist einen Torsionswinkel von 25,1(5)° auf. Die entsprechenden Winkel in Twistan betragen je 20°. Das tricyclische Gerüst von Aza-twistanon hat approximative C2-Symmetrie (Symmetrie von Twistan: D2).

Notes: The He(Iα) photoelectron spectra and the ionization energies of symmetrically substituted di-n-alkyl-diacetylenes R-(C≡C)2-R (with R = CH3, C2H5, n-C3H7, n-C4H9) are presented. The effect of the alkyl substitutents is that the two acetylenic ionization energies, Iv,1 and Iv,2, shift by the same amount, i.e. their difference Iv,2 - Iv,1 remains constant (2.45 ± 0.05 eV). Between 12.5 eV and 17 eV the band system in the photoelectron spectrum of R-(C≡C)2-R is superimposable with that in the spectrum of the corresponding alkane, RH, with the exception of a uniformly small shift of all the bands to higher ionization energy.

Notes: Alkoxychlorofluorocyclopropanes are easily prepared by chlorofluorocarbene addition to en-ethers in a two-phase system and converted by simple heating in an aqueous solvent mixture to 2-fluoro-2-alkenals which can be reduced to the corresponding alcohols.

Notes: (Z)-1-Alkylated propenes undergo metallation at an allylic site more rapidly than do their (E)-isomers, no matter in which configuration the resulting organometallic is thermodynamically more stable. A striking illustration is given by (Z)-4,4-dimethyl-2-pentenyl potassium which is formed 15 times faster than its (E)-isomer, although the latter is clearly favored under equilibrium conditions. The configurational reorganization of alkenylpotassium compounds in tetrahydrofuran solution is very slow. At least in one case, however, traces of oxygen efficiently catalyse the Z/E equilibration.

Notes: Conformational Analysis of Acylated 5,6,7,8-TetrahydropterinesThe conformation of N(5)-acetates, and of N(5)- and N(8)-trifluoroacetates, respectively, of 6-methyl- and cis-6, 7-dimethyl-tetrahydropterines is studied by 1H-NMR. spectroscopy. It is shown that the methyl group next to the acylated nitrogen atom is in quasi-axial position.

Notes: The base peak in the mass spectrum of several 1,4,2-benzoxazinone derivatives 1a-f (cf. Scheme 1 and the Table) suggests a clean carbon monoxide elimination leading to benzoxazole radical cations 2a-f. This benzoxazinone-benzoxazole conversion can be reproduced quantitatively by flash vacuum thermolysis.The isomeric 2,4,1-benzoxazinone 4 (cf. Scheme 2) eliminates carbon dioxide - the resulting biradical species 5 does not recombine to benzazete 10 but fragments into nitrile and benzyne (7).

Notes: Synthesis of alkylpyrrolo[1,2-a]pyrazines, roasted meat flavor constituentsSeven alkylpyrrolo[1,2-a]pyrazines have been identified for the first time in a roasted meat aroma obtained by thermolysis of the hydrosoluble flavor precursors of raw meat. Identification of individual components was done by capillary gas chromatography/mass spectroscopy coupling. The structure of these nitrogen heterocyclic compounds was for some time in doubt because of the similarity of the MS. with those of other diazaindene and diazanaphthalene derivatives such as benzimidazoles, indazoles, cyclopenta [b]pyrazines and dihydroquinoxalines. The structure of these new flavor components was completely elucidated in some cases by interpretation of NMR. spectra, the others being deduced by analogy. Hypotheses are formulated concerning the formation of this skeleton by a non-enzymatic browning reaction between carbohydrates and amino acids. Four different schemes have been adopted to synthesize substituted isomers selectively.

Notes: The second order rate constants (k) for quaternization of thirty 4-substituted quinuclidines (1) by methyl iodide in methanol have been measured. The effects of the substituents on rate are relatively small and indicate an early transition state with little charge separation. They also indicate less involvement of the nitrogen atom, i.e. a looser transition state, for quaternization by allyl halides than for the less reactive propyl halides. The log k values of 4-substituted quinuclidines correlate moderately well with their pKa values, the main reason being the imperfect correlation between nucleophilicity and basicity. The assumption that substituents exert equal effects on rates and equilibria is therefore only partly justified. Certain irregularities in the correlation can be attributed to a reduction of the nucleophilicity of nitrogen in 1 due to hydrogen bonding to the solvent methanol. Furthermore, quaternization is faster and responds more strongly to substituent effects in the aprotic solvent acetonitrile.

Notes: Acid Catalysed Rearrangement of 1,5-Dimethyl-6-methyliden-tricyclo[3.2.1.02,7]oct-3-en-8endo-olsThe tricyclic alcohols 2,3,4 and 6 (Scheme 1) are synthesized by the reaction of the tricyclic ketone 1 with sodiumborohydrid or metalloorganic reagents. Their configuration at C(8) is determined by NMR. in the presence of Eu(fod)3. The exo-attack of 1 by the nucleophil forming the endo-alcohol is favored, the π-electrons of C(3) = C(4) hindering the endo-attack. On treatment with sulfuric acid in dioxane/water at 25° the tertiary alcohols yield aryl-substituted ketones. 3 gives in 78.5% yield a mixture of the 3-(dimethylphenyl)-2-butanones 12 and 13, in addition to 16.5% of (2,3,4-trimethylphenyl)-2-propanon (14) (Scheme 2). The alcohols 4 and 6 yield mixtures of the 2-(dimethylphenyl)-3-pentanones 19 and 20 (72%), and 2-(dimethylphenyl)-propiophenones 21 and 22 (68%), respectively (Scheme 2). In the case of the secondary alcohol 2 mainly products derived from hydration at the C(6), C(9) double bond are formed, namely the mixture of diols 23 and 24 (21%), and the mixture of the isomeric 2-(dimethylphenyl)propanals 25, 26 and 27 (3%) (Scheme 3). - The structures of 12-14, 19/20, 21/22, 23/24 and 25/26/27 were established by spectroscopic data. In the case of 12 and 13 the degradation of their mixture to the known 1-(dimethylphenyl)ethanols 17/18 confirmed the assignment. - The most probable mechanism for the rearrangement of 3 is shown in Schemes 4 and 5. The reaction proceeds from 3 through a, b and g to 12 and 13; 14 is formed via e, f and i. In the case of 4 and 6 only the reaction analogue to 3 → a → b → g ⇉12/13 takes place. The isomeric aldehyds 25-27 formed from 2 could have the structures s, t, and v. The former two could be generated in a similar way as 12/13 from 3, the latter one as shown in Scheme 8.

Notes: Natural Vincamine (1) has been synthesized in an enantioselective manner starting from the ethylpentenal 7. In the key step a mixture of the diastereoisomeric racemates, 14 and 15, was directly obtained from the silyl enol ether 11 and the dihydro-β-carboline 12 by the way of an intramolecular Mannich reaction of the intermediate 13 (Scheme 4). The undesired stereoisomers, 14 and 15b, were recycled to 15a using the related reversible Mannich reaction 18 ⇄ 14 + 15, followed by crystallization of the salt from 15a and (+)malic acid. 15a was converted to natural vincamine (1) in several steps including the known transformation 20→1.

Notes: 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.

Notes: Synthesis and X-ray data of 3-hydroxy-N-methyl-hasubananA new simple way to synthesis 3-hydroxy-N-methyl-hasubanan (1c) is described and a single crystal X-ray structure analysis is presented.

Notes: Synthesis of amino-sugars using reductive amination reactions. Preliminary communicationTreatment of aldehydo- or keto-sugars with primary or secondary amines and hydrogen in the presence of a catalyst (Pd/C) gave with good to excellent yields (67-96%) the expected secondary or tertiary amines. Primary amines can be obtained by using benzylamine, a hydrogenolysis taking place during the reaction.

Notes: Irradiation of the tricyclic vinylcyclopropane 3 and Fe(CO)5 resulted in the formation of the s̰,π-bonded iron complex 7 and the π,π-bonded iron complex 8 (Scheme 2). Complex 8 was easily degraded with silica gel to give hydrocarbon 9, which reproduced 8 by photolysis in the presence of Fe(CO)5. Photolysis of 7 afforded a mixture of 3 (23%), 9 (27,5%), and three other hydrocarbons. Oxidative degradation of 7 with ceric ammonium nitrate in methanol gave the dimethoxy-hydrocarbon 10. - The tricyclic hydrocarbon 3 isomerized thermally to the bicyclic hydrocarbon 11 (with CH3—C(9) in an exo position) via a homosigmatropic [1,5]-H-shift. On the other hand, 3 was converted into the other isomer 14 (with CH3—C(9) in an endo position) by action of Mo(CO)6 or TsOH. Both isomers 11 and 14 reacted with 4-phenyl-1,2,4-triazoline-3,5-dione to give the isomeric Diels-Alder adducts 12 and 15, respectively, which were photochemically converted into the cage compounds 13 and 16, respectively (Scheme 3). - Photochemical reaction of the tricyclic vinylcyclopropane 6 with Fe(CO)5 gave the σ,π-bonded iron complexes 17 and 18. Heating of 17 at 80° resulted in a loss of one mol of carbon monoxide to give 18 in quantitative yield. Oxidative degradation of 17 with ceric ammonium nitrate in ethanol afforded the polycyclic lactones 19 and 20 by a novel type of reaction (Scheme 4). - The tricyclic ketone 21 was thermally converted into the α,β-unsaturated ketone 22 via a homosigmatropic [1,5]-H-shift. The configuration at C(7) of 22 was confirmed to be same as that of 11 (CH3—C(9) in an exo position) by chemical conversions: 22 was reduced with NaBH4 to alcohol 23 which, in turn, was dehydrated with POCl3/pyridine to 11 (Scheme 5). Reaction of ketone 21 with Mo(CO)6 gave the α,β-unsaturated ketone 25 and a cage compound X, whose structure was not fully elucidated. - Reaction of the polycyclic epoxide 26 with Fe2(CO)9 or Mo(CO)6 yielded the allyl alcohol 27 in a novel type of reaction. The epoxides 29 and 32 were similarly converted into the corresponding allyl alcohols 30 and 33, respectively (Scheme 6).

Notes: Physiological doses of insulin and glucagon in the range of 0.5-2.5 m unit and 0.05-2 μg respectively per 100 g body weight stimulate first and inhibit afterwards the cholesterol synthesis from labeled acetate in rat liver in vivo. It could be shown that these effects are not caused by a regulating influence of the HMG-coenzyme A reductase.

Notes: (1) Radioactivity of biosynthetically labeled squalene, injected in tracer amounts in rats is incorporated to about equal parts into cholesterol and component(s) of the fatty acid fraction of the liver. The ubiquinones isolated from the liver are radioactive and show about the same specific radioactivity as the cholesterol. It appears therefore, that the squalene which escapes incorporation into cholesterol is degraded to metabolite(s) suited for the synthesis of isoprene compounds.(2) Radioactivity of injected biosynthetically and chemically labeled cholesterol is traced in the ubiquinones and the squalene of rat liver indicating that a degradation of cholesterol and a recycling of the metabolite(s) occurs.(3) A recycling of metabolite(s) of squalene and of cholesterol can explain the observation that after labeled mevalonate or acetate as precursor, radioactivity can be traced in the squalene of the liver many hours after the injection and maintains a constant value during a period of several hours.(4) Radioactivity of biosynthetically labeled lanosterol is not only incorporated into cholesterol but a considerable part of it into component(s) of the bile acid fraction of the liver. Evidence is obtained that this transformation occurs by circumventing cholesterol as intermediate.

Notes: Three novel routes for the preparation of the dyestuff indigo are described. Two of the methods use isatoic anhydride, the third one styrene as starting materials. Key reactions are acylation of both dimsyl and nitromethane anions, Pummerer rearrangement and Nef reaction. A novel nitration of styrene is the basis of the third method.

Notes: A novel synthetic analog of adenosine: the 3′-deoxy-3′-C-dibromomenthylidene-adenosineThe title compound (7) has been prepared by a sequence of classical synthetic steps from 3-deoxy-3-C-dibromomethylidene-1,2: 5,6-di-O-isopropylidene-α-D-ribo-hexofuranose (1). The β-configuration of the nucleoside was established by formation of a cyclonucleoside. 7 is very slowly deaminated by adenosine deaminase. In contrast with its dichloro analog, it does not inhibit the growth of Escherichia coli.

Notes: 3-C-Methylxylofuranose Derivatives3′-C-methyladenosine has been known for almost ten years whereas its 3′-epimer is still to be prepared, because of the difficulty of synthesizing the 3-C-methylxylo-furanose. In this communication, the synthesis of 1,2-O-isoproypylidene acetal 9 and its derivatives is described. Vicinal dihydroxylation of 5-O-benzoyl-3-deoxy-1,2-O-isopryopylidene-3-C-methylidene-α-D-erythro-pentofuranose (6) led to the branchedchain sugar derivative 7 which was selectively tosylated to 8 whose reduction gave 9. These reactions, as well as the derivatizations of 7, 8 and 9, took place with good to excellent yields.

Notes: 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.

Notes: Kristalline und molekulare Struktur von trans-[(2-chlorphenyl)-1-benzocyclobutenyl]-(1,4,5,6-tetrahydro- pyrimidyl)-sulfid.Zur Abklärung von Konstitution und Konfiguration der Titelverbindung wurde eine Röntgenstrukturanalyse durchgeführt. Die Kristalle gehören zur monoklinen Raumgruppe C2/c, a = 17.221 (6), b = 7.846 (2), c = 25.031 (8) Å, β = 104.55 (2)°, Z = 8. Die Struktur wurde mit 2188 signifikanten Daten bis R = 0.055 verfeinert. Die mittlere Standardabweichung der Lagekoordinaten der C- und N-Atome beträgt 0.003 Å.

Notes: α-Aryl-o-xylyl dibromides 1 reacted with thioureas to give the mono-isothiouronium salts 2, bis-isothiouronium salts 4 being formed as by-products in some cases. Compounds 2, which readily reacted with water or alcohols to form 3, were cyclized with Na2CO3 in anhydrous acetone to yield 5-aryl-2,4-benzothiazepines 5, 6 and 7, but the 2′-chlorophenyl-derivative 21 exceptionally cyclized to the cyclobutene 20. The 1-aryl-2,4-benzothiazepines 14, 15 and 16 were prepared unequivocally by acid-catalysed cyclizations of thioureas 13 and 19.

Notes: Synthesis of (±)-LasiodiplodinThe synthesis of the plant growth inhibitor (±)-lasiodiplodin (VII), a 12 membered lactone of a substituted resorcylic acid is described. Condensation of methyl acetoacetate and methyl 11-hydroxy-2-undecenoate followed by treatment of the product with benzyl alcohol lead to the benzyl ether II which was aromatized via the benzeneselenenyl derivative. Methylation of the phenolic hydroxyl in III and conversion of the primary alcohol in the side chain into the secondary alcohol provided the hydroxy ester IV. The corresponding hydroxy acid V was transformed into the S-(2-pyridyl) carbothioate which cyclized under the influence of silver ions to yield 68% of 4-benzyl-lasiodiplodin (VI). Removal of the benzyl group by catalytic hydrogenation gave (±)-lasiodiplodin (VII).

Notes: Die Kristallstruktur und die molekulare Konformation in Lösung von 6-Phenyl- und 11-Phenyl-3,4,6,11-tetrahydro-2H-pyrimido-[2,1-c] [2,4]benzothiazepinDie Röntgenstrukturanalysen der beiden Titelverbindungen ergaben, dass die Konformation der Thiazepinringe zwar voneinander verschieden sind, dass aber in beiden Verbindungen der Phenylsubstituent in axialer Stellung steht. Interpretationen der 1H-NMR.-Daten legen die Vermutung nahe, dass die bevorzugten Konformationen des siebengliedrigen Ringes in Lösung in beiden Molekeln mit den im Kristall beobachteten Konformationen identisch sind.

Notes: Condensation of azetidinones 2a and 2b with mercaptan 3 gave respectively compound 10 or a 1:1 mixture of 17 and 17′. Bromination of 10, afforded cis and trans-bromohydrins 13a and of 17 and 17′ cis and trans-bromohydrins 18a. Acetylation and reduction with zinc and acetic acid of these bromohydrins gave cephems 4a or 4b and 4b′ respectively.

Notes: A simple mixing-reaction model has been developed [1] which allows a description and simulation of the coupling of the mass diffusion with the chemical reaction during the mixing process of two miscible reactant solutions. For competitive, consecutive as well as for competitive, parallel second-order reactions the general behaviour and the dependence of the product distribution on diffusion effects are calculated for semi-continuous reaction conditions using various simplifying assumptions. The usefulness of these assumptions is discussed with reference to the calculated predictions of two versions of the mixing-reaction model.

Notes: Synthesis of radioactive α-melanotropin derivatives containing a bromoacetyl or diazoacetyl group for studies of covalent hormone-macromolecule complexesα-Melanotropin derivatives and fragments covalently bound to human serum albumin through their N-terminal end exhibit almost the same biological activity as the corresponding free Nα-acetylated peptides [6]. The preparation of such complexes requires derivatives with a ‘reactive’ N-terminal acetyl group. We describe here the synthesis of three α-melanotropin fragments and of two specifically tritiated α-melanotropin derivatives containing Nα-bromoacetyl or Nα-diazoacetyl groups: BrCH2CO · Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val · NH2, BrCH2CO · Glu-His-Phe-Arg-Trp-Gly · OH, BrCH2CO · Trp-Gly-Lys-Pro-Val middot; NH2, BrCH2CO · D-Ala-Tyr(3H2)-Gly-Nva-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val · NH2, and N2 = CHCO · Gly-Tyr(3H2)-Ser-Nva-Glu-His-Phe-Arg-Trp-Gly- Lys-Pro-Val · NH2. The latter two analogues displayed a specific radioactivity of about 20 and 36 Ci/mmol, and a biological activity of 2 · 109 and 6 · 109 U/mmol respectively. They are also being used for affinity and photoaffinity labelling of receptor molecules and antibody combining sites.

Notes: The disguise of the intrinsic selectivity of competitive, consecutive reaction systems by the mixing process is demonstrated experimentally using the fast nitration of a number of aromatic compounds with nitronium salts in nitromethane. The measured product distributions were compared with the distributions predicted from our mixing-reaction model developed previously [2] [4]. This comparison enabled the relative intrinsic rate constants for the second nitration step of the aromatic compounds investigated to be determined.

Notes: The results of this study show that, for given initial and boundary conditions, four parameters are sufficient to describe the final product distribution of azo coupling reactions influenced by mixing. This is in agreement with the prediction of the mixing-reaction model developed previously [4] [5]. In order to explain the pH-dependence of the measured mixing-disguised product distribution, it is necessary to assume that a selectivity-determining, local pH-gradient exists even though the solution is macroscopically buffered.

Notes: A catalytic one step procedure for the C(1), C(2)-bond cleavage of long-chain aliphatic alcohols and ω-phenyl alcohols has been investigated, using as examples decanol, dodecanol, hexadecanol, benzyl alcohol, 2-phenylethanol and 3-phenyl-propanol. The reactions, which were carried out in a continuous flow tubular reactor using a Ni/Cu catalyst, showed good activity and selectivity with respect to the cleavage products. On the basis of the experimental studies a reaction scheme for the heterogeneous catalytic C(1), C(2)-bond cleavage of the alcohols is suggested.

Notes: 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.

Notes: The ligand exchange MX5·L + *L⇌MX5·*L + L for the octahedral adducts MX5·L, in an inert solvent (CH2Cl2 or CHCl3) with neutral ligands, proceeds via a dissociative D mechanism when M = Nb, X = Cl and L = phosphoryl compound. A dissociative interchange Id mechanism is suggested when M = Nb or Ta, and X = F. A first order rate law and positive values for ΔS* (+4 to +14 cal K-1 mol-1) are observed for the exchanges on the pentachloride adducts. However, a second order rate law and large negative values for ΔS* (-15 to -24 cal K-1 mol-1) are found for the intermolecular neutral ligand exchange (measured by 1H-NMR.) and for the intramolecular fluorine exchange (measured by 19F-NMR.) reactions on the pentafluoride adducts. The fluorine exchange is 2 to 5 times faster than the ligand exchange. The exchanges, on the pentachloride and on the pentafluoride adducts, are slowed down with increasing donor strength of the phosphoryl compound.

Notes: Reactions of Steroids with Dialkylaminosulfur Trifluorides. I. 11β-Hydroxysteroids.Reactions of three types of 11β-hydroxy steroids with dialkylaminosulfur trifluorides (DAST) have been studied. 9Δ-unsubstituted 11-alcohols are dehydrated with DAST to Δ9(11)-unsaturated compounds under very mild conditions. 9α-Chloro-11β-hydroxy steroids are quantitatively fluorinated in position 11 yielding the known 9α-chloro-11β-fluoro derivatives. Finally, 9α, 11Δ-fluorohydrins at 0-25° are selectively transformed with DAST into Δ11-9α-fluorides. When the latter reaction is run at lower temperature, the corresponding 11-piperidinesulfinates, products of partial hydrolysis of the alkoxy-dialkylaminosulfur difluoride intermediates postulated by Middleton, can be isolated in high yields. A rational explanation of the results is presented.

Notes: Tetracarbonyliron Complexes of trans-Cycloalkenes and trans-CycloalkadienesRelatively stable olefin tetracarbonyliron complexes were obtained by reaction of Fe2(CO)9 with trans-cyclooctene (t-1), trans-cyclononene (t-2) and trans-cyclodecene (t-3) (Scheme 2) in pentane solution at room temperature. Furthermore, trans,cis-cycloocta-1,5- and -1,3-diene (t,c-7 and t,c-8) as well as trans,trans,cis-2,8,12-trans-bicyclo[8.4.0]tetradecatriene (t,t,c-9) gave stable complexes only with the trans-configurated double bond (Scheme 3).An olefin tetracarbonyliron complex was also obtained with bicyclo[4.3.1]deca-7,9-diene (10) which reacted only at the strained bridge-head double bond. The IR. spectra of the new complexes are in agreement with an equatorial position of the olefinic ligands in the trigonal bipyramide of the iron.

Notes: The stereochemical structure of two reduction products of benzo[b]-5α-17β-hydroxy-androst-2-eno[2,3-e] [1,4]thiazine has been determined by 1H-NMR. Spectrometry using the INDOR technique.

Notes: Contribution to the asymmetric synthesis of bicyclic compounds catalysed by optically active amino acids. Synthesis of (S)-2-pyrrolidinepropionic acid and (R)-4-amino-5-phenylvaleric acidThe evaluation of literature data concerning the asymmetric cyclization of the prochiral monocyclic triketones 1 to the enediones 3 shows that catalysis with optically active α-amino acids of the (S)-series leads to an excess of products having the same absolute configuration as natural steroids at C (13), while those of the (R)-series favour the formation of the enantiomers (Scheme 1). With 1a as substrate an inverse asymmetric course was observed using the optically active β-amino acids 5, 8 and 10 as catalysts (Table 1). Furthermore, the synthesis of the optically active γ-amino acids 6 and 11 using the Arndt-Eistert process is described. The influence of these latter compounds on the asymmetric transformation of 1a into 3a has been investigated.