Epoxidation and reduction of DHEA, 1,4,6-androstatrien-3-one and 4,6-androstadien-3beta,17beta-diol

Dehydroepiandrosterone (DHEA) reacted with m-chloroperoxybenzoic acid(m-CPBA) to form 3beta-hydroxy-5alpha,6alpha-epoxyandrostan-17-one (1), but it did not react with 30% H2O2. 1,4,6-Androstatrien-3,17-dione (2) was obtained from DHEA and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane. Compound 2 was reacted with 30%H2O2 and 5% NaOH in methanol to give 1alpha,2alpha-epoxy-4,6-androstadien-3,17-dione (3),which was stereoselectively reduced with NaBH4 to form 1alpha,2alpha-epoxy-4,6-androstadien-3beta,17beta-diol (7) and reacted with Li metal in absolute ethanol-tetrahydrofuran mixture to give 2-ethoxy-1,4,6-androstatrien-3,17-dione (8). Compound 2 was also epoxidized with m-CPBA in dichloromethane to afford 6alpha,7alpha-epoxy-1,4-androstadien-3,17-dione (4),which was reacted with NaBH4 to synthesize 6alpha,7alpha-epoxy-4-androsten-3beta,17beta-diol (9).Compound 4 was reduced with Li metal in absolute ethanol-tetrahydrofuran mixture to form 7beta-ethoxy-6alpha-hydroxy-1,4-androstadien-3,17-dione (10). Compound 2 was reduced with NaBH4 in absolute ethanol to form 4,6-androstadien-3beta,17beta-diol (5), which was reacted with 30% H2O2 to give the original compound, but which reacted with m-CPBAto give 4beta,5beta-epoxy-6-androsten-3beta,17beta-diol (6).     

Solvent-dependent crystallization of 1-hydro-6-carbaphosphatrane and its tautomer

1-Hydro-6-carbaphosphatrane 2 was obtained as a mixture with its tautomer, 3. Tautomers 2 and 3 were isolated by the recrystallization from different solvents, respectively, and each structure was determined by X-ray crystallographic analysis. Variable-temperature NMR experiments revealed that pentacoordinate 2 and tricoordinate 3 are under the equilibrium, showing that 3 is more stable. The theoretical calculations found a weaker transannular PC bond in 2 than in 1-hydro-5-carbaphosphatrane, 1, which can be considered to be the reason 1-hydro-6-carba-phosphatrane 2 is less stable than its tautomer 3.     

Electrochemical Reduction of Cyclohex-2-enones

The electrochemical reduction of the cyclohex-2-enones 1a–1e (mercury cathode, CH₃CN, Bu₄NBF₄) was studied by means of cyclic voltammetry, d.c. polarography, coulometry and chemical product analysis. Compounds 1a–1c give a mixture of the hydrodimers 4 and 5 via formation of the radical anion 2 by an irreversible one electron transfer, followed by protonation and dimerization of the allylic radical 3 . The 6-halocyclohex-2-enones 1d and 1e exhibit two distinct reduction waves. The first corresponds to an irreversible two electron transfer with formation of the halide anion and the enolate anion 6 which gives 1b by protonation. The second wave corresponds to a quasi-reversible one electron transfer to 6 to afford the radical dianion 7 (Scheme 2).     

Enantioselective nitrile anion cyclization to substituted pyrrolidines. A highly efficient synthesis of (3S,4R)-N-tert-butyl-4-arylpyrrolidine-3-carboxylic acid

[reaction: see text] A practical asymmetric synthesis of N-tert-butyl disubstituted pyrrolidines via a nitrile anion cyclization strategy is described. The five-step chromatography-free synthesis of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (2) from 2-chloro-1-(2,4-difluorophenyl)-ethanone achieved a 71% overall yield. The cyclization substrate was prepared via a catalytic CBS asymmetric reduction, t-butylamine displacement of the chlorohydrin, and a conjugate addition of the hindered secondary amine to acrylonitrile. The key nitrile anion 5-exo-tet cyclization concomitantly formed the pyrrolidine ring with clean inversion of the C-4 center to afford 1,3,4-trisubstituted chiral pyrrolidine in >95% yield and 94-99% ee. Diethyl chlorophosphate and lithium hexamethyldisilazide were shown to be the respective optimum activating group and base in this cyclization. The trans-cis mixture of the pyrrolidine nitrile undergoes a kinetically controlled epimerization/ saponification to afford the pure trans-pyrrolidine carboxylic acid target compound in >99.9% chemical and optical purity. This chemistry was also shown to be applicable to both electronically neutral and rich substituted phenyl substrates.     

Synthesis, structure, and bonding properties of 5-carbaphosphatranes: a new class of main group atrane

1-Hydro-5-carbaphosphatrane (1) and 1-methyl-5-carbaphosphatrane (2), the first 5-carbon analogues of phosphatranes, were synthesized by a demethylation reaction of cyclic phosphinate 3. X-ray analysis revealed that 1 has a typical trigonal bipyramidal structure with hydrogen and carbon atoms at the apical position and three oxygen atoms at the equatorial positions, indicating that 1 is a phosphorane in the perfectly "anti-apicophilic" arrangement. Apical P-C and P-H bond lengths were 1.921(2) and 1.38(2) A, respectively. The (1)J(PH) value of 1 and the (1)J(PC)(P-CH(3)) value of 2 were 852 and 215 Hz, respectively, which are extraordinarily large for the apical coupling constants of phosphoranes, but close to those of the reported phosphatranes with a 5-nitrogen atom. IR and Raman spectra are also reported. Force constant calculations indicate the transannular bond in carbaphosphatrane is 3 times stronger than in silatrane, due to its covalent character.     

A facile and novel synthesis of 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-ones

A convenient and regioselective synthesis of a new heterocycle, 5-phenyl-1H or 3H-imidazo[4,5-c][1,8]-naphthyridin-4(5H)-one 1-a or 1-b , is described. Methyl 2-anilinonicotinate 15 was transformed into the valuable intermediate, N-phenyl-3-azaisatoic anhydride 4 using trichloromethyl chloroformate (TCF). Treatment of 4 with the anion of ethyl nitroacetate gave 4-hydroxy-3-nitro-1-phenyl-1,8-naphthyridin-4(5H)-one 3 . Compound 3 was chlorinated, aminated, reduced, and cyclized to afford 5-phenylimidazo[4,5-c][1,8]naphthyridin-4(5H)-one 1 . Regioselective substitution at the 1 or 3-position in the imidazole moiety of 1 was achieved by minor changes of the above scheme.     

Reactions of 1-Hydro-5-carbaphosphatrane: Tautomerization between Five-Coordinate and Three-Coordinate Species

Oxidation, sulfurization, and selenation of a 1-hydro-5-carbaphosphatrane afforded the corresponding cyclic phosphonate, cyclic phosphonothioate, and cyclic phosphonoselenoate, respectively. These results indicate the existence of the tautomerization between the five-coordinate 5-carbaphosphatrane and the three-coordinate cyclic phosphonite.     

Synthesis and properties of a novel cyclic sulfilimine, 2-methyl-2,4,1-benzodithiazin-2-ium-1-ide

A novel cyclic sulfilimine, 2-methyl-2,4,1-benzodithiazin-2-ium-1-ide ( 4 ) was synthesized by deprotonation of the corresponding azasulfonium salt ( 3 ) with base. The compound 4 was oxidized with potassium permanganate to afford the sulfoximine 5 , exclusively. On refluxing in several solvents, compound 4 underwent a ring contraction to afford benzothiazole ( 8 ) via the 1,2-imino shift. The reaction of 4 with a variety of electrophiles, such as dialkyl acetylenedicarboxylate, acylating agents, diphenylcyclopropenone, and phenyl isocyanate, afforded ringopened adducts. Synthetic approaches to cyclic disulfonium ylides are also described.     

The reaction of isothiocyanates with 2-cyanoethanoic acid hydrazide. A novel synthesis of 1,3,4-thiadiazoles

Benzoyl and ethoxycarbonyl isothiocyanates reacted with 2-cyanoethanoic acid hydrazide 2 to afford 1-cyanoacetyl-4-substituted thiosemicarbazide ( 5a,b ). Compound 5a afforded the pyrazolo[1,5-a]-s-triazine derivative 6 on treatment with 5% potassium hydroxide, and cyclised to 2-benzoylamino-5-cyanomethyl-1,3,4-thiadiazole ( 8 ) when boiled under reflux in glacial acetic acid. Compound 8 condensed with aromatic aldehydes to yield the corresponding arylidene derivatives 9a-c . It undergoes coupling with aromatic diazonium salts to afford the hydrazones 11a-c . Similarly, it coupled with diazotised aminopyrazole to afford the cyclic product 12 .     

Reversible skeletal transmetalations of inorganic rings: isolation of aluminatophosphazenes, a zwitterionic phosphazene, and a donor-stabilized alumazine-phosphazene hybrid cation

Synthesis of the cyclic aluminatophosphazene ring N(PCl2NMe)2AlMeCl (5) has been achieved via a skeletal transmetalation reaction between AlMe3 and the boratophosphazene N(PCl2NMe)2BCl2 (1). Reaction of 5 with various halogenated Lewis acids such as GaCl3 yielded the fully chlorinated aluminum heterocycle N(PCl2NMe)2AlCl2 (8) through a methyl-halogen exchange process. In contrast, treatment of 5 with excess AlMe3 resulted in complete methylation at aluminum to give N(PCl2NMe)2AlMe2 (6). Compound 5 was reacted with various Ag+ salts with weakly coordinating anions, including Ag[OSO2CF3], which afforded the triflate-substituted heterocycle N(PCl2NMe)2AlMe(OSO2CF3) (9). The reaction of 5 with Ag[BF4] surprisingly produced the previously known fluorinated boratophosphazene N(PCl2NMe)2BF2 (10). The transformation of 1 to 5 and then to 10 represents a rare, formally reversible, skeletal transmetalation process involving boron and aluminum. Treatment of 5 with Ag[PF6] led to the insertion of phosphorus in place of aluminum to form the novel zwitterionic fluorinated phosphorus(V) heterocycle N(PCl2NMe)2PF4 (11). The ethyl-substituted aluminatophosphazene N(PCl2NMe)2AlMeEt (14) reacted cleanly with a 1:1 mixture of [Ph3C][B(C6F5)4] and THF to give the novel donor-stabilized alumazine-phosphazene hybrid cation, [7.THF]+, as the [B(C6F5)4]- salt [N(PCl2NMe)2AlMe.THF][B(C6F5)4] (15).     

Furopyridines. II. Bromination and nitration of furo[2,3-b]-, furo[3,2-b]-, furo[2,3-c]- and furo[3,2-c]pyridine

In order to reveal the reactivities of furopyridines, we undertook bromination and nitration of four furopyridines ( 1, 2, 3 and 4 ) whose chemical properties had been almost unknown. Bromination of 1, 2, 3 and 4 gave the corresponding trans-2,3-dibromo-2,3-dihydro derivatives 6, 8, 10 and 12 , respectively, which were converted to 3-bromofuropyridines 7, 9, 11 and 13 by treatment with sodium hydroxide in aqueous methanol. Nitration of 1 with a mixture of fuming nitric acid and sulfuric acid afforded a mixture of addition products 14a, 14b and 14c and 2-nitro derivative 15 . Both 14a and 14b were easily converted to 15 by treatment with sodium bicarbonate. Compound 2 was nitrated to give a mixture of cis- and trans-2-nitro-3-hydroxy-2,3-dihydro derivative 16a and 16b and 2-nitro derivative 17 . The cis isomer 16a was transformed to the trans isomer 16b by refluxing on silica gel in ethyl acetate. Compound 16b was dehydrated with acetic anhydride to give 17 . Nitration of 3 gave a nitrolic acid derivative 20 . Nitration of 4 gave a mixture of 2-nitro derivative 22 and 3-(trinitromethyl)pyridin-4-ol ( 23 ). The structures of 20 and 23 were established by single crystal X-ray analysis. The differences of behavior observed in these reactions are discussed in connection with the results of the determination of pKa values and the relative reactivities of deuteriodeprotonation of these furopyridines.     

Synthesis of New Polyfused Thienopyrimidine,Thienopyridine, Thienothiazine,Thienoxazine, and Thienodiazepine Derivatives

3,4-Diamino-2-carbethoxy-5-cyanothieno(2,3-b)thiophene (1) was treated with ethylenediamine to afford 3,4-diamino-2,5-bi[2-(4,5-dihydro-1H-imidazole-2-yl]-thieno(2,3-b)thiophene 2 , which in turn was treated with chloroacety chloride to give bis[imidazolothieno diazepine] derivative 3 and with each of p-chlorobenzaldehyde, triethyl orthoformate, and Lawesson's reagent (LR) to yield bis[imidazolothienopyrimidine] derivatives 4-6 . Compound 1 was subjected to Mannich reaction to afford Mannich bases 7 and 8a , b . The later products ( 8a , b ) were treated with malononitrile yielding 9a and 9b . Treatment of compound 1 with CS 2 , NaOH and CH 3 I produced compounds 10 and 11 . The reaction of compound 10 with each of o-aminothiphenal, o-phenylenediamen, hydrazine hydrate, and phenylhydrazine afforded compounds 12a , b , 13a , b . Compound 1 was allowed to react with CS 2 , phenyl (benzoyl)isothiocyanate and phenylisocyanate to get the described products 14-19 , respectively. On reacting compound 1 with ethylcyanoacetate thieno(2,3-b)pyridine derivative 21 was obtained through the intermediate 20 . Finally, compound 1 was treated with malononitrile to yield compound 22 .     

双(三甲硅基环戊二烯基羰基钼)配合物的合成和结构

通过三羰基(三甲硅环戊二烯基)钼负离子盐[η-M~e~3sic~5H~4Mo(CO)~3]^-Li~+氧化偶联合成了Mo-Mo键双核化合物(1),在甲苯中回流制得含Mo≡Mo 叁键化合物(2),乙炔对这Mo≡Mo键加成形成四面体形配合物(3),经元素分析.IR和~1HMR谱表征了标题化合物的结构.并用X射线衍射测定了配合物[η-M~e~3sic~5H~4Mo(CO)~3]~2(1)的晶体结构.1为单斜晶系,空间群为P2~1/c,晶体学数据:a=1.2826(2),b=0.8211(5),c=1.2902(1)nm,β=1.0480(2)°,V=1.3138nm^3,Z=2,D~ x= 1. 604g.cm^-^3,μ=10.530cm^-^1,F(000)=636.硅桥联双[三羰基(三甲硅基环戊二烯基)钼]负离子盐E[η-M~e~3sic~5H~4Mo(CO)~3]~2^2^-Li^+~2,[E=SiMe~2, O(SiMe~2)~2],也用类似方法合成化合物4,5,也经元素分析.IR.^1HNMR表征.     

Synthesis and Antimicrobial Activity of Polyfunctionally Substituted Heterocyclic Compounds Derived from 5‐Cinnamoylamino‐2‐Cyanomethyl‐1,3,4‐Thiadiazole

Cinnamoyl isothiocyanate 1 was reacted with 2‐cyanoethanoic acid hydrazide 2 to afford 1‐cyanoacetyl‐4‐substituted thiosemicarbazide 3, which on treatment with a mixture of glacial acetic acid and acetic anhydride gave the desired 5‐cinnamoylamino‐2‐cyanomethyl‐1,3,4‐thiadiazole 4 . Compound 4 was subjected to react with aromatic aldehydes, phenylisothiocyanate, carbon disulphide, and arylidene malononitrile to give coumarin 5 , thiazolidines 8 , 9, and 1,3,4‐thiadiazolo[3,2‐a]pyridine 13 derivatives. The structures of all synthesized compounds were ascertained by spectral and analytical data. Antimicrobial activity of some of prepared compounds was investigated, and compounds 7, 8 were found to exhibit the highest strength.     

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.     

A Novel Synthesis of Some 1,4‐Phenylene‐bis‐heterocyclic Derivatives and of Some Pyran,Pyrano[2,3‐c]pyrazole,and Pyrano[2,3‐d]pyrimidine Derivatives [1]

p‐Diacetyl benzene 1 undergoes bromination to afford p‐bromoacetyl phenacyl bromide 2 . Compound 2 reacts with twofold excess of malononitrile to afford 2‐{2‐[4‐(3,3‐Dicyanopropionyl)‐phenyl]‐2‐oxo‐ethyl}‐malononitrile 3 . Compound 3 could be cyclized to afford the 1,4‐phenylene‐bis‐furan derivative 4 . Compound 3 reacts also with a twofold excess of hydrazine hydrate and phenyl hydrazine under dry conditions at RT to afford the bis‐pyrazole derivatives 5a , 5b , respectively. The reaction of 5a , 5b with the same reagents in refluxing dioxane afforded the bis‐pyrazolopyridazine derivatives 7a , 7b , respectively. The azo coupling of compound 3 with arene diazonium salts afforded the bis‐pyrazole derivatives 9a , 9b , 9c . The β‐keto esters 10a , 10b react with benzaldehyde and malononitrile in a one pot synthesis to afford the pyran derivatives 11a , 11b . These latter compounds react with hydrazine hydrate and urea derivatives to afford the pyrano[2,3‐c]pyrazoles 15a , 15b and the pyrano[2,3‐d]pyrimidine derivatives 17a , 17b , respectively.     

Structural diversity, optical and magnetic properties of a series of manganese thioarsenates with 1,10-phenanthroline or 2,2'-bipyridine ligands: using monodentate methylamine as an alkalinity regulator

The exploration in two hydro(solvo)thermal reaction systems As/S/Mn(2+)/phen/methylamine aqueous solution and As/S/Mn(2+)/2,2'-bipy/H(2)O affords five new manganese thioarsenates with diverse structures, namely, (CH(3)NH(3)){[Mn(phen)(2)](As(V)S(4))}·phen (1 and 1'), (CH(3)NH(3))(2){[Mn(phen)](2)(As(V)S(4))(2)} (2), {[Mn(phen)(2)](As(III)(2)S(4))}(n) (3), {[Mn(phen)](3)(As(III)S(3))(2)}·H(2)O (4), and {[Mn(2,2'-bipy)(2)](2)(As(V)S(4))}[As(III)S(S(5))] (5). Compound 1 comprises a {[Mn(phen)(2)](As(V)S(4))}(-) complex anion, a monoprotonated methylamine cation and a phen molecule. Compound 2 contains a butterfly like {[Mn(phen)](2)(As(V)S(4))(2)}(2-) anion charge compensated by two monoprotonated methylamine cations. Compound 3 is a neutral chain formed by a helical (1)(∞)(As(III)S(2)(-)) vierer chain covalently bonds to [Mn(II)(phen)](2+) complexes via all its terminal S atoms. Compound 4 features a neutral chain showing the stabilization of noncondensed (As(III)S(3))(3-) anions in the coordination of [Mn(II)(phen)](2+) complex cations. Compound 5 features a mixed-valent As(III)/As(V) character and an interesting chalcogenidometalates structure, where a polycation formed by the connection of two [Mn(2,2'-bipy)(2)](2+) complex cation and a (As(V)S(4))(3-) anion acts as a countercation for a polythioarsenate anion, [As(III)S(S(5))](-). The title compounds exhibit optical gaps in the range 1.58-2.48 eV and blue photoluminescence. Interestingly, compound 1 displays a weak second harmonic generation (SHG) response being about 1/21 times of KTP (KTiOPO(4)). Magnetic measurements show paramagnetic behavior for 1 and dominant antiferromagnetic behavior for 2-5. Of particular interest is 4, which is the first manganese chalcogenide showing spin-canting characteristic.     

三级醇的脱水及C-乙酰化反应

冰乙酸—乙酸酐—高氯酸体系通常用作醇的快速乙酰化,也曾用于醇的脱水反应,但我们发现三级醇类化合物在上述体系中可以形成双键的乙酰化产物,收率颇高,因此,我们做了一些探索。     

Synthesis of Some New Polyfused Thienothiophenes Part 4: Synthesis of Thienopyrimidine,Thienotriazine, Thienoimidazotriazine,Thienotriazolotriazine, and Thienotetrazolotriazine Derivatives

3,4-Diamino-2,5-dicarboxamidothieno(2,3-b)thiophene 1 was allowed to react with CS 2 , carbonyl compounds, ethyl chloroformate, S,S-acetals, and oxallyl chloride to give thienopyrimidines 2-6 and thieno-1,4-diazepine 7 . Treatment of compound 1 with nitrous acid afforded compound 8 , which converted into the corresponding chloro derivative 9 by using PCl 5 . Compound 9 was reacted with amino reagents to afford the corresponding thienoimidazotriazines 10 and 11 , thienotriazolotriazines 12 and 13 and 4-hydrazinothienotriazine 14 . Treatment of compound 14 with aldehydes, triethyl orthoformate, CS 2 , nitrous acid and ylidenemalononitriles, afforded thienotriazolotriazine 16-18 , thienotetrazolotriazine 19 , and 4-pyrazolyl-thienotriazine 20-22 derivatives respectively.     

(+)-菊花烯酮的Baeyer-Villiger反应

Baeyer-Villiger反应是酮在过氧酸氧化下形成酯的反应,是有机反应中合成酯的主要方法,这一反应可应用在环酮扩环形成含氧杂环内酯的反应上．由于反应是立体控制的,已广泛应用于天然产物,例如：抗生素、类固醇和信息素中间体的合成,某些用其它方法难以合成的羟基酸可由内酯水解得到。