Catalytic decomposition of branched α'-phenoxy-α-iazo ketones affording 2, 8h-cyclohepta[b]furan-3-one and 2h-cyclohepta[b]furan-3a(3ah)methyl-3-one

The decomposition induced by bis(hexafluoroacetoacetonato)Cu II on branched α-diazo ketones 1 bearing a phenoxy group at the α'-carbon has been investigated. The course of the reactions has been shown to be dependent upon substitution. Mixtures of furanones 2 and chromanones 4 were obtained from α-unsubstituted substrates 1b–d, as in the case of 1a. Instead, among the α-mono substituted substrates 1f and 1g selectively gave cycloneptatrienes 3f and 3g, respectively, while 1e and 1h gave mixtures of the corresponding 3 and 4. Cycloheptatrienes 3 easily rearranged to chromanones 4. The intermediacy of norcaradienes 5 has been tentatively proposed in the catalytic decomposition of 1, and in rearrangement of 3e–h to 4e–h.     

Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides

Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a′, 1b′, 1a and 1b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a′, 2b′, 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside. These photosensitizers were characterized by ¹H, ¹³C and ¹⁹F NMR spectroscopies and elemental analysis. The photocytotoxicity of the S-glycosylated photosensitizers and the parent porphyrin (1) and chlorin (2) was examined in HeLa cells. Photosensitizers 1, 2, 1a′, 1b′, 2a′ and 2b′ showed no significant photocytotoxicity at the concentration of 0.5 μM, while the deprotected photosensitizers 1a, 1b, 2a and 2b were photocytotoxic. The strong inhibition by sodium azide of the photocytotoxicity of these photosensitizers suggested that ¹O₂ is the main mediator. The S-glucosylated photosensitizers 1a and 2a showed higher photocytotoxicity than S-galactosylated 1b and 2b, respectively. The cellular uptake of 1a and 2a increased up to 24 h, while that of 1b and 2b was saturated by 12 h.     

Functionalized enamines—XIV : Reaction of α-tetralone enamines with carbenes influence of the nature of carbene and the base-component of the enamine on the reaction pattern

Enamine Ia, derived from 6-methoxy-1-tetralone and morpholine, reacts with carbenes¹2a and 2b to give (1:1) adducts 3a, and a mixture of 3b and 3c, respectively. The pyrrolidine enamine 1b, on the other hand, reacts with carbene 2b, to give, beside the (1:1) adduct 3e, benzylidene-derivative 4b. Reaction of enamine 1b with carbene 2a does not yield a 1:1 adduct; instead, two products were isolated which have been identified as 4a and 5. Both morpholine and pyrrolidine enamines 1ab, react with carbene 2c to give one and the same product 6. Possible mechanisms for the formation of the reaction products are discussed.     

The structures of macbecin I and II : New antitumor antibiotics

Macbecin I 1, C₃₀H₄₂N₂O₈, and macbecin II 2, C₃₀H₄₄N₂O₈, were shown to be 2,6-disubstituted benzoquinone and hydroquinone derivatives by an oxidation-reduction relationship, UV. ¹H and ¹³C NMR spectra. Alkaline methanolysis of 1 gave a 2-aminobenzoquinone derivative 5, suggesting an ansa-structure for 1, and acid hydrolysis of 1 gave decarbamoyl products 9,10 and 11, indicative of the location of carbamoyloxy group in allylic position. Spin decoupling studies on 1,3 and 5clarified the partial structures [A], [B], [C] and [D]. From their mutual disposition two structures 1a and 1b, were proposed out of which 1a has been selected for the structure of 1 on the basis of the structure of oxidative degradation product 12. X-Ray analysis of the bromoacetyl derivative of 1 confirmed the above proposed structure and determined the absolute stereochemistry of 1 and 2.     

Nitrileketenimine tautomerism in substituted alkylidene malononitriles and alkylidene cyanoacetates: A characteristic UV absorption band

Several alkylidene malononitriles (1b,1d,1e,2b and4b) and alkylidene cyanoacetates (1a,2a and4a) studied exhibit a long wavelength UV absorption band around 355 nm which shows a hyperchromic effect in the presence of ethanolic alkali. This band has been assigned to the ketenimine tautomer (5). Addition of water to1b,1e and2b gives the corresponding pyridine diols (7a,7b and8a) respectively. Similarly, addition of ethanol to1e and2b gave the corresponding ethoxypyridine derivatives (7c and8b). Mechanism of formation of these compounds is discussed. Structures, as well as mechanism of formation of1c,7c and10 obtained from1b,1e and2b respectively on standing at room temperature are also discussed.     

Enamine chemistry—XXV: Reduction of enaminones by LiAlH4 and NaBH4. Synthesis of α,β-unsaturated aldehydes

Cyclohexanone, 2-methyl-cyclohexanone and 4-methyl-cyclohexanone, 1, were transformed into the enaminones 4a–4e by the following two routes: (A): Acylation of the enamines, 2, derived from 1 and secondary amines (pyrrolidine, morpholine and piperidine) by ethyl chloroformate, and (B): Condensation of 1 with diethyl oxalate, giving the β-ketoesters 3, followed by reaction with the secondary amines. Ethyl 2(-1-pyrrolidinyl)-1-cyclopentene-1-carboxylate, 4f, and methyl 3-(1-pyrrolidinyl)-2-butenoate, 4g, were prepared from ethyl 2-oxo-1-cyclopentanecarboxylate and ethyl 3-oxo-butanoate, respectively, by condensation with pyrrolidine. Reduction of 4a by LAH afforded 1-cyclohexen-1-carboxaldehyde, 5a, 1-cyclohexene-1-methanol, 6a, and 1-(1-cyclohexene-1-methyl)pyrrolidine, 7a, in yields depending on the molar ratio of LAH/4a. Reduction of 4f by LAH gave cyclopentene-1-methanol, 6b, 1-(1-cyclopentene-1-methyl)pyrrolidine, 7b, and ethyl-2(1-pyrrolidinyl)-1-cyclo-pentanecarboxylate, 8b. Compound 4g, when reduced with LAH, yielded methyl 3-(1-pyrrolidinyl) butanoate, 8c (main product) and 1-(2-butenyl)pyrrolidine, 7c (minor). Reduction of 4 by NaBH₄ afforded exclusively the saturated β-aminoesters, 8 in high yields. The reductions with LAH and NaBH₄ are rationalized in terms of the HSAB principle.     

Synthesis of silicon-functionalized 7-silanorbornadienes and their thermolysis and photolysis

A series of 7-silanorbornadienes were prepared and characterized by X-ray crystallographic analysis. 2,3-Benzo-7-mesityl-1,4,5,6-tetraphenyl-7-silanorbornadiene (1a) was prepared by the [4+2] cycloaddition reaction of 1-mesityl-2,3,4,5-tetraphenyl-1-sila-2,4-cyclopentadiene (4) with benzyne. 7-Hydro 1a was converted into 7-chloro-substituted silanorbornadiene 1b. Treatment of 1b with lithium phenylamide and lithium phenylthiolate gave 7-phenylamino-substituted silanorbornadiene 1c and 7-phenylthio-substituted silanorbornadiene 1d, respectively. Reductive lithiation of 1b with lithium naphthalenide afforded 7-lithiated silanorbornadiene 1f, which reacted with chlorotrimethylsilane to give 7-trimethylsilyl-substituted silanorbornadiene 1e. Stereochemistry at the bridging silicon during these transformations was determined by X-ray crystallographic analysis. Thermolysis of 1 produced corresponding silylenes 5, which were trapped with triethylsilane to give disilanes 6. Photolysis of 1 except 1c also afforded corresponding silylenes 5. Theoretical calculation of the models of silanorbornadienes was performed at the MP2/6-31+G(d, p) level.     

Synthesis and odor properties of Phantolide analogues

Phantolide analogues 1a–1d were newly synthesized to evaluate their odor profiles. The enantiomers of 1a and 1b were also synthesized. Both (S) enantiomers of 1a and 1b had musk odor although weakly, and but neither of the (R) enantiomers 1a and 1b had musk odor. During the investigations, we encountered the undesirable racemization in Friedel-Crafts reaction of the intermediate (S)-5.     

Bromination of 3-phenylindoles

Brominations of 3-phenylindole (1a) and its 1-methyl-(1b) and 1-acetyl-(1c) derivatives with NBS in AcOH and CCl₄ have been carried out. In AcOH 1 gave 2-bromo derivatives (2) in high yields and the relative reactivity was found to be NH > NMe ? NAc by competitive reactions. In boiling CCl₄1a and 1b gave 2 but bromination of 1c did not proceed. Bromination of 1a with 2 moles of NBS in AcOH gave 2,6-(major) and 2,5-dibromides (8 and 9). Reaction of 2a with thiourea gave 19. Selective reduction of the bromine atom at the 2-position in 2,6-dibromide (10) was achieved by Zn3CuNaOH, and irradiation of 8 in EtOH-alkali reduced 2,6-dibromide to 1a.     

Reactions of ketenes with ethoxyalkynes: Synthesis of 2,2,4-trialkylcyclobutane-1,3-diones

Treatment of dimethyl ketene with ethoxyacetylene 1a, 1-ethoxyoct-1-yne 1b, and 1-ethoxytetrade-1-yne 1c afforded the 3-ethoxycyclobutenones 2a–c. Hydrolysis of 2a–c with dilute hydrochloric acid gave the cyclobutane-1,3-diones 3a–c. The ¹H NMR spectra of these compounds indicate that in CDCl₃ solution 2,2-dimethylcyclobutane-1,3-dione 3a exists as the diketone, whereas the 2,2,4-trialkylcyclobutane-1,3-diones 3b and 3c exist as the monoenols.     

Silacyclohexadienylanionen bis- und tris-trimethylsilyl)-silacyclohexadiene

1,1-Dialkyl(1,1-diaryl)-4-R-1-silacyclohexadienyl anions (1) are available by ether cleavage of the corresponding, 1,1-dialkyl(1,1-diaryl)-4-methoxy-4-R-1-silacyclohexa-2,5-dienes (4), or by deprotonation of the 1,1-dialkyl(1,1-diaryl)-4-R-1-silacyclohexa-2,4-dienes (3) - which are available from 4 - with n-BuLi or LDA resp.The anions 1 are regioselectively silylated by trimethylchlorosilane to give the 6-trimethylsilyl-1-silacyclohexa-2,4-dienes (7,8), their alkylation or acylation occurs exclusively in 4-position to 16 or 17 resp.Deprotonation of 7, 8 with n-BuLi gives the 2-trimethylsilyl-1-silacyclohexadienyl (9), with trimethylchlorosilane they react regioselectively to give the 2,6-bis(trimethylsilyl)-1-silacyclohexa-2,4-dienes (10, 11), with alkyl halides and ketones the anion 9 reacts only in the 4-position.The 1-silacyclohexa-2,5-dienes 22, 25, 28 substituted at the silicon atom by functional groups (O-i-Prop) or by hydrogen can be transformed into 2,6-bis(trimethylsilyl)-1-silacyclohexa-2,4-dienes 24, 27, 33 resp., if LDA is used as base.The easily formed 4-R-2,6-bis(trimethylsilyl)-1-silacyclohexa-2,4-dienyl anions (by deprotonation of 10, 11, 24, 27, 33 with LDA) react with trimethylchlorosilane regioselectively to give the 4-R-2,4,6-tris(trimethylsilyl)-1-silacyclohexa-2,5-dienes 37. Accessing 37 succeeds very simply by manifold-silylation of the 1-sila-2,4-cyclohexadienes 38 with excess trimethylchlorosilane in the presence of 3 mol LDA.Owing to trimethylsilyl substitution in the 2,6-position of the 1-silacyclohexa-2,4-dienes, the ring-silicon atom is strongly sterically shielded, therefore reactions of functional groups at the silicon atom are restricted.     

Solvent-dependent reactivities of acyclic nitrones with β-diketones: catalyst-free syntheses of endiones and enones

Reactions of the nitrones ^?O⁺N(Me)C(H)Ar 1 (Ar=phenyl 1a, 4-methylphenyl 1b, 2,4,6-trimethylphenyl 1c, and anthracen-9-yl 1d) with the cyclic β-diketones 1,3-indandione 2 or barbituric acid 3 in CH₂Cl₂, afford the corresponding endiones 2′a–2′d or 3′a–3′d. In contrast, dimedone 4 reacts with 1a or 1b to give the endione 4′a or 4′b and the bis-adduct 4″a or 4″b. Nevertheless, reaction of 4 with 1c or 1d in CH₂Cl₂ furnishes only the endione adducts 4′c or 4′d. However, the reaction of 4 with 1a or 1b in methanol gives only 4″a or 4″b, respectively. Among acyclic β-diketones only malonic acid 7 reacts with 1a–1c. Reaction of 7 with 1a in CH₂Cl₂ forms cinnamic acid 7″a, whereas in the case of 1b, the endione 7′b and (E)-3-p-tolylacrylic acid 7″b are obtained. The nitrone 1c reacts with 7 in CH₂Cl₂ to afford the endione 7′c or with acetone yielding (E)-4-mesitylbut-3-en-2-one 8. X-ray analyses are reported for 4′c, 5, and 7″b. In addition, the calculated acidity of the hydrogen at the α-C atom is shown to correlate with the reactivity of the β-diketones with nitrones.     

Reactions of thioketen s-oxides with diazo compounds : A novel synthesis of heterocyclic sulfines

Thioketen S-oxides 1 react with 2-diazopropane (2a) to give 1-pyrazoline-4-thione S-oxides 3 Addition of diazomethane to 1 yields a stable 1:1-adduct only from the S-oxide 1c. The constitution of both types of cycloadducts (3, 11) was proven by X-ray diffraction. Irradiation of 3 leads to loss of nitrogen to afford the alkylidene thiirane S-oxides 12.     

Aminomethinylierung H-aktiver verbindungen in der reihe analgetischer wirkstoffe

Electrophilic attack of the active methylene group in 3-methyl-1-phenyl-5-pyrazolone (2) by s-triazine (1) leads to aminomethinylation of 2 with formation of 3-methyl-1-phenyl-4-aminomethylene-5-pyrazolone (4). Subsequent interaction of 4 with 2 explains the formation of 4,4′-methenyl-bis-[3-methyl-1-phenyl-5-pyrazolone (5). 1-Phenyl-3,5-pyrazolidinedione (6) reacts analogously with 1 forming 1-phenyl-4-aminomethylene-3,5-pyrazolidinedione (7). N,N′-Bis-indanyl-formamidine (9) results from the interaction of 2-amino-indane (8) with 1.     

Cyanoacetanilides intermediates in heterocyclic synthesis. Part 6: Preparation of some hitherto unknown 2-oxopyridine,bipyridine, isoquinoline and chromeno[3,4-c]pyridine containing sulfonamide moiety

Treatment of cyanoacetanilide derivative 1 with tetracyanoethylene (2) in dioxane/triethylamine furnished 2-pyridone derivative 6. Aminopyridine 9 was obtained by cyclization of compound 1 with ketene dithioacetal 7/EtONa. Cyclocondensation of 1 with malononitrile and/or acetylacetone (1:1 M ratio) gave pyridine derivatives 11 and 13. Ternary condensation of compound 1, aliphatic aldehydes and malononitrile (1:1:1 M ratio) yielded the 2-pyridones 20a and b. Bipyridines 22a–c were prepared by refluxing of compound 21 with active methylene reagents. Cyclization of chromene derivatives 24 and 28 with malononitrile produced the novel chromeno[3,4-c]pyridine 26 and pyrano[3′,2′:6,7]chromeno[3,4-c]pyridine 29.     

The constitution of vertinolide,a new derivative of tetronic acid,produced by Verticillium intertextum

From the culture of Verticillium intertextrum a new tetronic acid derivative, vertinolide, has been isolated as the main constituent of the chloroform extract. Structure 1a was established for vertinolide by X-ray diffraction analysis. Vertinolide (1a) was also transformed to an O-methyl-(1b), an O-acetyl-(1c), a tetrahydro- (1d) and a tetrahydro-O-methyl-derivative (4). The spectroscopic properties of 1a, of its derivatives 1a, 1c, 1d and 4 as well as of three model compounds are compared and discussed.     

Steady-state and nanosecond spectroscopic studies of triplet sensitized reaction of K-region arene oxides

Photorearrangement reactions of K-region arene oxides, 9,10-epoxy-9,10-dihydrophenanthrene (1a), 3-acetyl-9,10-epoxy-9,10-dihydrophenanthrene (1b), and 3,4-epoxy-3,4-dihydropyrene (1c) in dichloroethane (DCE) solution were investigated by steady irradiation and nanosecond transient spectroscopy. Photorearrangements producing substituted oxepins, 2 occur via the singlet excited state of these compounds, while the phenolic products, 9-hydroxyphenanthrene (3a), 3-acetyl-9-hydroxyphenanthrene (3b), and 4-hydroxypyrene (3c) are formed via the triplet state. Phenol 3 formation from the triplet 1 sensitized by the triplet 3 (i.e. product sensitization) is proposed for the photorearrangement reactions of 1a and 1c, and this process is the only way phenol (3a) is formed because of the negligible intersystem crossing probability of 1a. No product sensitization occurs in the photorearrangement reaction of 1b.     

The synthesis of octavalene (tricyclo[5.1.0.02,8]octa-3,5-diene) and several substituted octavalenes

The first synthesis of octavalene (1a) is reported. The starting material is homobenzvalene (5), to which monobromocarbene is added. The resulting compound 3a takes up bromine across the central bicyclo[1.1.0]butane bond to form the tribromide 7a which undergoes a cyclopropyl bromide-allyl bromide rearrangement on heating. From the product (1Oa) HBr is eliminated to give a 1,3-dibromocyclobutane with a 1,3-butadiene bridge across its 2- and 4-position (11a). Finally, t-butyllithium removes the two Br atoms from 11a and converts it into a 4:1 mixture of 1a and cyclooctatetraene. This reaction sequence represents the first application of protective group strategy in bicyclo[1.1.0]butane chemistry. Octavalene (1a) is shown to rearrange to cyclooctatetraene at 50°. Deuterium-labeled 1a ([1,8-D₂] 1a) is used to prove that a [1,5]-sigmatropic shift does not occur in 1a. Utilizing the above methodology 4-bromooctavalene (1b) and 3-phenyl-5-bromooctavalene (1c) are synthesized from the dibromocarbene adducts 3b and c of homobenzvalene (5) and 5-phenylhomobenzvalene (6), respectively. Surprisingly, 1c was accompanied by a small quantity of 3-bromo-1-phenyloctavalene (1d). Possible mechanisms for the addition of bomine to the bicyclo[1.1.0]butane system of compounds 3 and for the formation of the octavalenes 1 are discussed. In the ¹³C-NMR spectra of 1 and 11 chemical shifts at unexpectedly high field are observed for C-6 of the 1,3-cycloheptadiene moieties.     

Diphenyl N-halosulfilimines : Preparation,decomposition, and reactions with nucleophiles

Diphenyl N chloro (l)-N bromo (2) and N-iodo-sulfilimines (3) were prepared by halogenation of diphenyl free sulfilimine. Compound 1 decomposed in benzene at room temperature. The decomposition of 1 is a chain reaction since the reaction was induced by chlorine or t-butyl hypochlorite affording diphenyl(diphenylsulfilimino) sulfonium chloride(4a) while it was inhibited by styrene or stilbene. Compound 4a was also obtained by the reaction of 1 with diphenyl sulfide in benzene. Decomposition of 1 in acetic acid proceeded smoothly affording various products. Compound 1 reacted with sulfides sulfoxides triarylphosphines and triethylamine affording the N-substituted iminosulfonium salts. Compounds 1 and 2 were hydrolyzed with sodium hydroxide affording diphenyl sulfoximine. The reaction of 1 with sodium cyanide gave diphenyl N cyanosulfilimine(17). The reaction of 1 with Grignard reagent gave diphenyl free sulfilimine. Compounds 2 and 3 are more stable than 1. Decomposition of 2 in benzene or acetic acid gave diphenyl(diphenylsulfilimino)sulfonium perbromide(4c)     

Total synthesis of (±)-desmethylhexahydrovallesiachotaminelactones

Total synthesis of (±)-desmethylhexahydrovallesiachotaminelactones 1a and 1b, and their isomers 2a and 2b is described. The formation of other epimeric pairs of lactones (1a and 3a, and 1b and 3b) from vallesiachotamine 4 is also described.