Modified Coumarins. II. Mannich Reaction of Substituted 4-Phenylcoumarins

Aminomethylation of 5-hydroxy- and 7-hydroxy-4-phenylcoumarins by substituted 1,1-diaminomethanes is studied. Mannich condensation of amino acids and their esters with 7-hydroxy-4-phenylcoumarin gives a series of 8-aminoacylmethylcoumarins and 4-phenyl-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones     

Cp2V] migration along an octatetrayne chain: from the monometallic complex (Cp2V(2-4eta-tBuC triple bond C2-C triple bond CC triple bond CtBu)] to the dimetallic complex

The oxidative addition of one equivalent of [Cp2V] (4) to the tetrayne ligand tBuC triple bond CC triple bond CC triple bond CC triple bond CtBu (5) gives the monometallic complex [Cp2V(3-4eta-tBuC triple bond C-C2-C triple bond CC triple bond CtBu)] (7). Compound 7 reacts further with a second equivalent of [Cp2V] to give the dimetallic complex [(Cp2V)2(1-2eta:7-8eta-tBuC2-C triple bond CC triple bond C-C2tBu)] (8), which involves a shift of the first coordinated [Cp2V] unit from the internal C3-C4 to the external C1-C2 positions on the alkynyl ligand. Compound 8 is also directly obtained by the addition of two equivalents of [Cp2V] to 5. Reversibly, reaction of 8 with 5 leads to 7. This exchange reaction between 7 and 8 by adding successively 5 and 4 has been monitored by EPR spectroscopy. By contrast, the oxidative addition of one or two equivalents of [Cp2V] to the tetrayne ligand PhC triple bond CC triple bond CC triple bond CC triple bond CPh (6) gives the homodimetallic complex [(Cp2V)2(1-2eta:7-8eta-PhC2-CC triple bond CC triple bond C-C2-Ph)] (9). Both monometallic and dimetallic complexes 7, 8, and 9 have been characterized by X-ray diffraction. Magnetic moment measurements for 8 and 9 from 300 to 4 K indicated a weak antiferromagnetic J exchange coupling of -12.5 and -4.1 cm(-1), respectively.     

Alkaloid studies. VI. lithium aluminum hydride reduction of apoyohimbine and the synthesis of 3,4,5,6-tetradehydroyohimbane-16-methanols

Catalytic reduction of apoyohimbine ( 1 ), prepared from yohimbine and thionyl chloride in pyridine, gives methyl yohimbane-16α-carboxylate ( 2 ) after equilibration with methoxide. LAH reduction of 2 or β-yohimbine O-tosylate ( 3 ) gives yohimbane-16α-methanol ( 4a ). LAH reduction of 1 affords yohimbane-16α-carboxaldehyde ( 5 ), yohimb-16-ene-16-methanol ( 6a ) and yohimbane-16β-methanol ( 7a ). Structural assignments 6a and 7a are confirmed by mass spectral measurements. Pmr spectra of 4a, 6a and 7a and their O-acetates 4b, 6b and 7b are discussed. LAH reduction of apo-α-yohimbine ( 8 ) affords alloyohimb-16-ene-16-methanol ( 9 ). Dehydrogenation of 4a with palladium black and maleic acid gives 3,5,4,5,6-tetradehydroyohimbane-16α-methanol ( 10 ) iodide, and 7a gives 3,4,5,6-tetradehydroyohimbane-16β-methanol ( 11 ) iodide and picrate. Properties of 10 and 11 differ from those of melinonine E.     

Synthesis in the diazasteroid group XI. A convenient route to the 4,8-diazasteroid system

The reaction of 1,6-naphthyridine 3 with acetic anhydride results in the formation of the 1:1 adduct 4 . Upon catalytic hydrogenation followed by acid hydrolysis and esterification, 4 affords 7 as an A-B steroid ring system synthon in moderate yield. Upon condensation with cyclopentanone and cyclohexanone, 7 , gives the 4,8-diazasteroid system 8 and the D-homo compound 9 , respectively.     

Polynuclear heterocyclic compounds. XIX. Reduction of 3,3,6,6-tetramethyloctahydroacridine-1,8-diones

Reduction in alcohol solution, using hydrogen at atmospheric pressure and platinum oxide catalyst, of 3, 3, -6, 6-tetramethyl-1, 2, 3, 4, 5, 6, 7, 8-octahydroacridine-1, 8-dione and its 9-phenyl derivative gives the corresponding 3, 3, 6, 6-tetramethyl-1, 2, 3, 4, 5, 6, 7, 8, 9, 10-decahydroacridine-1, 8-dione and its 9-phenyl derivative.For part XVIII see [1].     

Synthesis and antimicrobial activity of some new coumarin and dicoumarol derivatives

PTC reaction of coumarin derivative 1 with alkyl halides afforded C₄ oxygen alkylation products 2a-d in appreciative yield, whereas with phenyl isothiocyanate gives the C₃ addition product 4 ; also, one-pot three-component PTC reaction was investigated. Treatment of coumarin 1 with aromatic aldehydes in different molar ratios gives 3-arylidene derivatives 7a,b and the dicoumarol derivatives 8a,b . Pyrano chromene 9 and pyrano pyridine 10 were obtained by reaction of arylidene 7a with ethyl acetoacetate through Michael cycloaddition reaction. The stability of pyrone ring in 3-arylidene 7 and dicoumarol 8 towards different nucleophilic reagents under reflux and/or fusion conditions has been studied by the action of hydrazine hydrate, ammonium acetate, methyl amine, and p-toluidine afforded compounds 11 and 13a-c . The antimicrobial activity of some synthesized compounds has been investigated.     

Photochemische Reaktionen. 85. Mitteilung [1]. Zur Photochemie von α, β-Epoxy-eucarvon

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

Polyhedral monocarbaborane chemistry. Some C-phenylated seven, eight, nine, ten, eleven and twelve-vertex species

Some synthetic and structural systematics for monocarbaboranes, using the C-phenylated motif as the example, are investigated. The 10-vertex [6-Ph-nido-6-CB(9)H(11)](-) anion 1, from reaction of PhCHO with B(10)H(14) in KOH/H(2)O, is a useful entry synthon into C-phenyl monocarbaborane chemistry. Treatment of anion 1 with Na/thf yields the 10-vertex [1-Ph-closo-1-CB(9)H(9)](-) anion 2a, whereas treatment of anion 1 with iodine in alkaline solution yields the isomeric 10-vertex [2-Ph-closo-2-CB(9)H(9)](-) anion 2b, which isomerises quantitatively to 2a on heating under reflux in DME. Thermolysis of anion 1 yields the 9-vertex [4-Ph-closo-4-CB(8)H(8)](-) anion 5, whereas treatment of anion 1 with FeCl(3)/HCl gives neutral 9-vertex [4-Ph-arachno-4-CB(8)H(13)] 3. Compound 3 gives neutral 9-vertex [1-Ph-nido-1-CB(8)H(11)] 4 in refluxing toluene, and gives the 7-vertex [2-Ph-closo-2-CB(6)H(6)](-) anion 7 and the 8-vertex [1-Ph-closo-1-CB(7)H(7)](-) anion 6 in refluxing toluene with NEt(3). Reaction of 1 with [BH(3)(thf)] yields the 11-vertex [7-Ph-nido-7-CB(10)H(12)](-) anion 8 which can be converted to the 12-vertex [1-Ph-closo-1-CB(11)H(11)](-) anion 10 using [BH(3)(SMe(2))]; alternatively, anion 1 yields anion 10 directly on treatment with [BH(3)(NEt(3))]. Treatment of anion 8 with I(2)/KOH yields the 11-vertex [2-Ph-closo-2-CB(10)H(10)](-) anion 9. The structures of anions 1, 2a, 2b, 5, 6, 7, 8, 9 and 10 have been established by single-crystal X-ray diffraction analyses of their [NEt(4)](+) salts, and those of neutral 3 and 4 estimated by DFT calculations at the B3LYP/6-31G* level; similar calculations have also been applied to the new anionic closo species 2a, 2b, 5, 6, 7, 9 and 10. Crystals of the [NEt(4)](+) salt of the [2-Ph-closo-2-CB(6)H(6)](-) anion 7 required synchrotron X-radiation for sufficient diffraction intensity for molecular-structure elucidation. The syntheses are in principle generally applicable to give extensive derivative C-aryl and C-alkyl chemistries.     

Unsymmetrical three-carbon condensations with dimedone

Condensing together equimolecular amounts of dimedone, an aldehyde, and ß-aminocrotonic ester gives derivatives of 3-ethoxycarbonyl-2, 7, 7-trimethyl-5-keto-1, 4, 5, 6, 7, 8-hexahydroquinoline (IVa-c); of these, compounds IVb and IVc can be oxidized by chromic anhydride to 3-ethoxycarbonyl-2, 7, trimethyl-5-keto-5, 6, 7, 8-tetrahydroquinolines (Vb, c). The UV and IR spectra of compounds IVc and Vc are determined. Oxidation splits IVa to bisdimedonylmethane (VI).     

青蒿乙素的化学转化

本文报道青蒿乙素(2)的若干化学转化,如:青蒿乙素的催化氢化得到三个化合物5,6,7.6与三氟化硼-乙醚配合物反应生成8和9.6用硷水解以及2,6,7分别与五羰基铁进行脱氧反应,得到相应的化合物18,3和4。     

Synthesis of profluorescent isoindoline nitroxides via palladium-catalysed Heck alkenylation

The synthesis of a new structural class of isoindoline nitroxides (aminoxyls), accessible via the palladium-catalysed Heck reaction, is presented. Reaction of the aryl bromoamine, 5-bromo-1,1,3,3-tetramethylisoindoline (4) or dibromoamine, 5,6-dibromo-1,1,3,3-tetramethylisoindoline (5) or the analogous bromonitroxides 6 and 7 with methyl acrylate gives the acrylate substituted tetramethylisoindoline amines 8 and 10 and nitroxides 12 and 14. Similarly, the reaction of the aryl bromides and dibromides 4-7 with methyl 4-vinylbenzoate gives the carboxystyryl substituted tetramethylisoindoline amines 9 and 11 and the analogous nitroxides 13 and 15. The carboxystyryl tetramethylisoindoline nitroxides demonstrate strongly suppressed fluorescence, which is revealed upon removal of the free radical by reduction or radical coupling.     

Stereochemistry of the Conversion of 1,3-Chloroalcohols in Alkaline Medium. The Chemistry of 1,3-Bifunctional Systems. XXII

The transformations of isomeric 1,3-chloroalcohols 1–4 , with cyclohexane skeleton, were studied in aqueous solution containing barium hydroxide. As regards the compounds with cis-configuration, 1 gives the oxetane 5 by intramolecular nucleophilic substitution, while 3 gives the unsaturated alcohols 7 and 8 by elimination. In the case of the trans-isomers 2 and 4 , fragmentation reactions occur in competition with elimination. The main reaction kinetic parameters of the transformations of the four compounds were determined.     

Hetarylnitrenes V. Reactions of Tetrazolopyrazine Ring Contraction of Nitrenodiazines in Solution. Preliminary communication

Thermolysis of tetrazolopyrazine ( 1 ) in organic solvents gives pyrazinylnitrene ( 2 ) which undergoes ring contraction to 1-cyanoimidazole ( 3 ). 7-Methyl-5-methylthio-tetrazolo[1,5-c]pyrimidine ( 4 ) likewise gives 1-cyano-2-methylthio-4-methyl-imidazole ( 6 ). The two tetrazoles also undergo ring contraction to 1-cyanoimidazoles by gas chromatography, and 1 gives a low yield of 3 by photolysis. Thermolysis of 1 and 4 in cyclohexane gives aminopyrazine ( 7 ) and 6-amino-4-methyl-2-methylthio-pyrimidine ( 8 ), respectively. Tetrazolo[1,5-a]pyrimidines ( 9 ) give only 2-aminopyrimidines ( 10 ). 1-Cyanoimidazole, formed by thermolysis of 1 in acetic acid, reacts further to give 1-acetylimidazole, which with more acetic acid gives imidazole and acetic anhydride. An earlier report [2] of ring expansion of pyrazinylnitrene in acetic acid is discredited. In protic deuteriated solvents (D₃O, CH₃OD), tetrazolopyrazine reacts as an enamine, specifically exchanging H? C(6) for deuterium.     

Formation of 6-formyl-7-hydroxy-8-methoxycoumarin and 5,8-dioxopsoralen by reaction of 8-methoxypsoralen with H2O2 and potassium superoxide (KO2) catalyzed by halogenated or perhalogenated 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides

The oxidation of 8-methoxypsoralen (2) with hydrogen peroxide and potassium superoxide catalyzed by 5,10,15,20-(2,4,6-trimethylphenyl)porphyrinatoiron(III) chlorides [Me12TPPFe(III)Cl] (1a) and 5,10,15,20-(2,6-dichlorophenyl)porphyrinatoiron(III) chlorides [Cl8TPPFe(III)Cl] (1b) in dichloromethane gives 6-formyl-7-hydroxy-8-methoxycoumarin (3) in moderate yields, whereas the oxidation of (2) with H2O2 catalyzed by 5,10,15,20-(2,6-dichlorophenyl)-beta-octahaloporphyrinatoiron(III) chlorides [Cl8betaX8TPPFe(III)Cl] (X=Cl, Br) (1c, 1d) gives specifically 5,8-dioxopsoralen (4) in moderate yields.     

Oligonucleotide duplexes containing N8-glycosylated 8-aza-7-deazaguanine and self-assembly of 8-aza-7-deazapurines on the nucleoside and the oligomeric level

The 8-aza-7-deazaguanine N8-(2'-deoxy-beta-D-ribofuranoside) (1) was synthesized, converted into the phosphoramidite 4 and incorporated into oligonucleotides. Nucleoside 1 forms stable base pairs with 2'-deoxy-5-methylisocytidine in DNA with antiparallel chain orientation (aps) and with 2'-deoxycytidine in duplexes with parallel chains (ps). According to the CD spectra self-complementary oligonucleotides d(1-m5isoC)3 and d(1-C), form autonomous DNA-structures. Neither the nucleoside 1 nor the regularly linked 8-aza-7-deaza-2'-deoxyguanosine form G-like tetrads while the regularly linked 8-aza-7-deaza-2'-deoxyisoguanosine gives higher molecular assemblies which are destroyed by bulky 7-bromo substituents. This was verified on monomeric nucleosides by ESI-MS spectrometry and on oligonucleotides by HPLC analysis.     

Ring closures from eneearbamoyl azides. Syntheses of tetrahydro-3-indazolinones and 4-imidazolin-2-ones

Reaction of phosgene with cyclohexylidene amines gives good yields of (1-eyclohexen-l-yl)-carbamoyl chlorides ( 1 ). Compound 1 can be converted to the corresponding eneearbamoyl azide ( 2 ), which on pyrolysis gives an improved synthesis of 1-substituted-4,5,6,7-tetrahydro-3-indazolinones ( 7 ). When 1 is substituted by an allylic rather than alkyl or aryl group, the major products are 4-imidazolin-2-ones ( 8 ) accompanied by only minor amounts of 7 . The thermolysis reaction has been extended to N-allylcarbamoyl azides in general, thus providing a new and facile synthesis for 1,4-disubstituted 4-imidazolin-2-ones (9). A tentative mechanism is advanced, involving intermediate azide addition to the allylic double bond.     

Nitration of 2,3′-bithienyl

The nitration of 2,3′-bithienyl ( 1 ) with fuming nitric acid in acetic anhydride at 0° gives a mixture of 3-nitro- ( 2 ), 2′ -nitro- ( 3 ) and 5-nitro-2,3′-bithienyl ( 4 ) with relative percentages of 38.7%, 34.8% and 26.5%. When the nitration of 1 was carried out with fuming nitric acid in acetic acid at 20°, the same compounds 2, 3 and 4 were obtained, but with different relative percentages: 20.4%, 36.5% and 43.1% respectively. The results of the mononitration of 1 are compared with those obtained in other electrophilic substitutions and with the theoretical predictions. The further nitrations of 2, 3 and 4 with nitric acid in acetic anhydride at room temperature lead to the formation of five dinitro-2,3′-bithienyl isomers. Compound 2 gives a mixture of 2′,3-dinitro- ( 5 ) and 3,5′-dinitro-2,3′-bithienyl ( 6 ); compound 3 gives a mixture of 5 , 2′,5-dinitro- ( 7 ) and 2′,4-dinitro-2,3′-bithienyl ( 8 ); compound 4 gives 7 and 5,5′-dinitro-2,3′-bithienyl ( 9 ). The possible reasons of the formation of the various dinitro-2,3′-bithienyl isomers are discussed.     

Rearrangement of 5’,6’,7’,8’-tetrahydro-1’H-spiro(cyclohexane-1,2’-quinazolin)-4’(3’H)-one during the Vilsmeier reaction

Treatment of 5’,6’,7’,8’-tetrahydro-1’H-spiro(cyclohexane-1,2’-quinazolin)-4’ (3’H)-one with POCl3 and DMF gives a mixture of 1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile and 4,5-diformyl-2,3,6,7,8,10-hexahydroacridine-8a(1H)-carbonitrile, both products resulting from cascade transformations of the primary Vilsmeier intermediates.     

Synthesis of some new indolizines

The reaction between 4‐dimethylaminopyridine (DMAP) and 2‐bromoacetophenone(s) readily gives 1‐ [2‐(4‐substitutedphenyl)‐2‐oxoethyl]‐4‐(dimethylamino)pyridinium bromide ( 1–14 ). Action of aqueous NaOH on 1–8 generates the corresponding pyridinium ylide ( 15–22 ), which is isolated as a colored stable crystalline solid. Addition of 15–22 to dimethylacetylene dicarboxylate (DMAD) gives dimethyl 3‐(substitutedbenzoyl)‐7‐(dimethylamino)indolizine‐1,2‐dicarboxylate ( 23–30 ) in 46–62% yield.     

On the formation and solvolysis of 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines

The condensation of aryl methyl ketones 6 with acetic anhydride 4a in the presence of the boron trifluoride-acetic acid adduct 7 gives rise to the formation of 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines 8 in satisfactory yields. The stable 4-aryl-2,2-difluoro-6-methyl-1,3,2-(2H)-dioxaborines 8 can be transformed by hydrolysis into the corresponding aroylacetones 9. The reaction was optimized so as to avoid the formation of by-products, such as 2,4-diaryl-6-methylpyrylium tetrafluoroborates 11 or self-condensation products. © 1997 John Wiley & Sons, Inc.