New derivatives of 4,5-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrazole, 4,5-dihydro-1,2-oxazole,and pyrimidine prepared proceeding from (<Emphasis Type="Italic">E</Emphasis>)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one

Condensation of acetylferrocene with 5-phenyl(4-methylphenyl)-1,2-oxazole-3-carbaldehydes afforded (Е)-3-[5-phenyl(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-ones. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with semicarbazide, thiosemicarbazide, and hydroxylamine led to the formation of 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole- 1-carboxamide, 5-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-3-ferrocenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide, and 5-(4-methylphenyl)-3'-ferrocenyl-4',5'-dihydro-3,5'-bi-1,2-oxazole respectively. Reactions of (Е)-3-[5-(4-methylphenyl)-1,2-oxazol-3-yl]-1-ferrocenylprop-2-en-1-one with guanidine and thiourea result in 4-[5-(4-methyl-phenyl)-1,2-oxazol-3-yl]-6-ferrocenylpyrimidin-2-amine and -2-thione respectively.     

1-Thiocarbamoyl(ferrocenyl)-4,5-dihydropyrazoles

Thiosemicarbazide reacts with aryl -ferrocenylvinyl ketones and -arylvinyl ferrocenyl ketones in the presence of Bu^tOK to give 1-thiocarbamoyl-5- and -3-ferrocenyl-4,5-dihydropyrazoles, respectively. The complexes of 3-ferrocenyl-5-phenyl-, 3,5-diferrocenyl-, and 3-ferrocenyl-5-p-methoxyphenyl-1-thiocarbamoyl-4,5-dihydropyrazoles with Cu^II are described.     

1-二茂铁基-3-(4-烷氧基-3-溴苯基)-1,3-丙二酮的合成及其结构表征

由乙酰基二茂铁(1)与4-长链烷氧基-3-溴苯甲酸甲酯(2)通过酮酯缩合反应, 合成了1-二茂铁基-3-(4-烷氧基-3-溴苯基)-1,3-丙二酮(3). 标题化合物3为首次合成, 具有复杂的共振结构．通过元素分析、红外光谱、核磁共振氢谱对其结构进行了表征. 用X射线单晶衍射法测定了1-二茂铁基-3-(4-十二烷氧基-3-溴苯基)-1,3-丙二酮(3c)的结构, 结果表明: 晶体属于三斜晶系, P-1空间群, a＝0.8677(5) nm, b＝0.8791(5) nm, c＝2.1444(11) nm, α＝101.489(9)°, β＝94.784(10)°, γ＝102.522(9)°, V＝1.5511(14) nm3, Dc＝1.273 g&#8226;cm－3, μ＝1.801 mm－1, F(000)＝618, Z＝2, R1＝0.0597, wR2＝0.1386.     

3-Ferrocenyl-3-(1-naphthyl)cyclopropene. Synthesis, structure, and chemical transformations

Crystalline 3-ferrocenyl-3-(1-naphthyl)cyclopropene was prepared by dehydrobromination ofZ- andE-2-bromo-1-ferrocenyl-1-(1-naphthyl)-cyclopropanes by Bu^tOK in DMSO. The resulting compound and the startingZ-monobromocyclopropane were characterized by X-ray diffraction analysis. The obtained cyclopropene reacts with 1,3-diphenylisobenzofuran to give a [4+2]-cycloadduct. The small ring opens upon treatment with HBF₄ etherate to afford isomericZ- andE-prop-1-enes and 1-ferrocenyl-3H-benzo[e]indene. Thermolysis of this cyclopropene results in the formation of 1-ferrocenyl-9bH-benzo[e]indene. In all cases, opening of the small ring is accompanied by exclusive alkylation of the naphthalene moiety. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 499–506, March, 1998.     

3-Ferrocenyl-1-methyl- and 1-ferrocenyl-3-methylcyclopropenes

Dehydrobromination of isomeric 3-bromo-1-ferrocenyl-2-methylcyclopropanes afforded 3-ferrocenyl-1-methyl- and 1-ferrocenyl-3-methylcyclopropenes. These undergo smooth opening of the three-membered ring to give 1- and 2-ferrocenylbuta-1,3-dienes and 1- and 2-methyl-1H-cyclopentaferrocenes; with 1,3-diphenylisobenzofuran they give the classical Diels-Alder adducts.     

Synthesis and properties of 5-ferrocenyl-1H-pyrazole-3-carbaldehydes

New ferrocene derivatives - ethyl esters of 1-aryl-5-ferrocenyl-1H-pyrazole-3-carboxylic acids were synthesized. The corresponding aldehydes were obtained from acid esters in two steps. The reductive amination reaction of 5-ferrocenyl-1-phenyl-1H-pyrazole-3-carbaldehyde was studied. Several of these compounds were investigated by cyclic voltammetry. All of them exhibited a reversible one-electron oxidation-reduction wave owing to the ferrocene-ferricinium redox couple with a positive shift (0.51-0.69 V) compared with that of ferrocene (0.46 V). The X-ray crystal structure of the ethyl ether 1-(3-chloro-2-fluorophenyl)-5-ferrocenyl-1H-pyrazole-3-carboxylic acid is also presented.     

Fragmentation and 1,2-Addition Reactions upon Action of Methyllithium on Coupling Products of Ferrocenecarbaldehyde with Dibenzoylmethane

2-Ferrocenylmethylidene-1,2-diphenylpropanedione (3), 2,4-dibenzoyl-3-ferrocenyl-1,5-diphenylpentane-1,5-dione (4), and 2,4-dibenzoyl-3-ferrocenyl-2-[(ferrocenyl)hydroxymethyl]-1,5-diphenylpentane-1,5-dione (5) react with MeLi to undergo fragmentation and 1,2-addition or only 1,2-addition at the carbonyl group. Dehydration of intermediate tertiary alcohols affords α-methylstyrene (6), 3-ferrocenyl-1-phenylprop-2-enone (7), 3,5-diferrocenyl-1-phenyl-4-(1-phenylvinyl)cyclohexene (8), 3-ferrocenylmethylidene-2,4-diphenylpenta-1,4-diene (9), 2-benzoyl-1-ferrocenyl-3-phenylbuta-1,3-diene (10), 2-benzoyl-1-ferrocenyl-3-methylindene (11), 4-ferrocenyl-2-methyl-2,6-diphenyl-3,4-dihydro-2H-pyran (19), and (Z,Z)-2,4-dibenzoyl-1,3-diferrocenyl-5-phenylhexa-1,4-diene (21), isolated by chromatography. The spatial structures of ferrocenyldihydropyran (19) and diferrocenylhexadiene (21) were established by X-ray diffraction analysis.     

3-Alkenyl-5-ferrocenyl-2-pyrazolines in reactions with azodicarboxylic acidN-phenylimide

Azodicarboxylic acidN-phenylimide reacts with 1-acetyl-3-(2-ferrocenylethenyl)-5-ferrocenyl-2-pyrazoline according to the [4+2]-cycloaddition mechanism to form a Diels—Alder adduct. Under analogous conditions, 1-acetyl-5-ferrocenyl-3-(1-cyclohexenyl)-substituted 2-pyrazolines containing allylic hydrogen atoms give monoene addition products. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 908–913, May, 2000.     

Synthesis of rel-(3RS,3aSR,7aSR)-3-(4-Chlorophenyl)-3a,4,5,6,7,7a-hexahydro-1-methylindolin-6-one,the Main Metabolite of the Analgesic Ro 15-8081: A Potent Amine-Uptake Inhibitor

The synthesis of the title compound 2 and its diastereoisomer 3 was accomplished using tricarbonyl[1-5-n-(4-methoxycyclohexa-2,4-dien-1-yl)]iron tetrafluoroborate ( 4 ) as a precursor to the cyclohexanone ring. The assignments of the relative configurations of 2 and 3 are based on the X-ray analysis of compound 3 . Both compounds 2 and 3 are potent inhibitors of neuronal noradrenaline uptake in rats with similar potencies in vitro as compared to amitriptyline and desipramine. Compounds 2 and 3 are less potent as serotonin-uptake inhibitors, very weak inhibitors of dopamine uptake, and virtually devoid of antinociceptive activity.     

Synthesis, structures and reactions of some metallocene alcohols

E-1-Ferrocenyl-4,4-dimethylpent-2-ene-1-one has been synthesised from the Friedel-Crafts acylation of ferrocene with E-3-tert-butylacryloylchloride and converted to 1-ferrocenyl-3-chloro-4,4-dimethylpentan-1-one using ethereal hydrogen chloride. This new chloro ketone has been converted into three new ferrocene alcohols: 1-ferrocenyl-3,4-dimethyl-4-hydroxypentan-1-one, 1-ferrocenyl-3-chloro-4,4-dimethylpentan-1-ol, and 2,2,6,6-tetramethyl-3-ferrocenyl-5-chloroheptan-3-ol. A new dinuclear ferrocene derivative, E,E-2,2,9,9-tetramethyl-5,6-diferrocenyl-deca-3,7-diene, was isolated after treatment of 1-ferrocenyl-3-chloro-4,4-dimethylpentan-1-ol with acidic alumina; its structure was confirmed by X-ray crystallography, whilst electrochemistry revealed metal-metal interactions of similar magnitude to those seen for other 1,2-bis(ferrocenyl)ethane derivatives. Crystal structures have also been determined for 2,2,6,6-tetramethyl-3-ferrocenyl-5-chloroheptan-3-ol, rac-1-hydroxy[3]ferrocenophane, rac-1S,3S-1,3-diphenyl-1-hydroxy[3]ferrocenophane, and of rac-1,1^′-diphenyl-1,1^′-(1,1^′- ruthenocenediyl)dimethanol and show an intramolecular Cl?H-O hydrogen bond, a tetramer based on O?H-O hydrogen bonds, no hydrogen bonding, and a dimer with inter- and intramolecular O?H-O hydrogen bonds, respectively.     

The influence of phenolic hydroxy substitution on the electron transfer and anti-cancer properties of compounds based on the 2-ferrocenyl-1-phenyl-but-1-ene motif

The ferrocenyl compound 2-ferrocenyl-1,1-bis(4-hydroxyphenyl)-but-1-ene (), is very cytotoxic against breast cancer cells (IC(50) = 0.44 microM against MDA-MB-231). We now report the synthesis of a new series of para- and meta- substituted mono- and di- ferrocenyl phenols [2-ferrocenyl-1-(3-hydroxyphenyl)-1-phenyl-but-1-ene (), 2-ferrocenyl-1-(3-hydroxyphenyl)-1-(4-hydroxyphenyl)-but-1-ene (), 1,2-di-ferrocenyl-1-(4-hydroxyphenyl)-but-1-ene (), and 1,2-di-ferrocenyl-1-(3-hydroxyphenyl)-but-1-ene ()] and their electrochemical and biochemical properties, especially in comparison to the previously reported "standard" compounds [2-ferrocenyl-1-(4-hydroxyphenyl)-1-phenyl-but-1-ene () and ()]. We also report the synthesis and characterization of the diphenyl analogue, 2-ferrocenyl-1,1-diphenyl-but-1-ene (). This structure-activity relationship study was motivated by our hypothesis that the cytotoxicity of is related to its ability to form a quinone methide structure after two in situ 1-electron oxidations, a process which requires the presence of at least one p-phenol. The mono-ferrocenyl compounds (including those previously reported) are reasonably well recognized by the oestrogen receptors alpha (RBAs = 0.9-9.6%) and beta (RBAs = 0.28-16.3%), although the bulkier di-ferrocenyl compounds show very little affinity. In vitro, the cytotoxic effects of the phenolic complexes are related to the positioning of the hydroxyl group (para- superior to meta-), and to the number of ferrocenyl groups (one superior to two), with IC(50) values against the MDA-MB-231 cell line ranging from 0.44-3.5 microM. On the hormone-dependent breast cancer cell line MCF-7, the observed effect seems to be the result of two components, one cytotoxic (antiproliferative) and one estrogenic (proliferative). Electrochemical studies show that only the compounds with a p-phenol engage in proton-coupled intramolecular electron transfer.     

Synthesis, structure and biological activity of 1-(1-methoxy-1-ferrocenyl-3-arylpropan-2-yl)-1H-1,2,4-triazole derivatives

A total of eleven new 1-(1-methoxy-1-ferrocenyl-3-arylpropan-2-yl)-1H-1,2,4-triazole derivatives have been synthesized from acetylferrocene. The structures of the title compounds have been determined by elemental analysis, ¹H-NMR and single crystal X-ray diffraction analysis. Bioassay showed that some of the title compounds had high plant-growth regulatory activity. __________ Translated from Chinese Journal of Organic Chemistry, 2005, 25(8) (in Chinese)     

Synthesis of (E)-2-(1-ferrocenylmethylidene)malonic acid derivatives by a cobalt-catalyzed domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines

The domino reaction of ethyl diazoacetate, carbon monoxide and ferrocenylimines was investigated in the presence of Co₂(CO)₈ as catalyst. In most cases the main products are 2-(1-ferrocenylmethylidene) malonates formed by an N(1)-C(4) cleavage of the primarily derived β-lactams. The latter compounds could only be isolated when the reaction was carried out at relatively low CO pressure, using an excess of ethyl diazoacetate. trans-N-(tert-Butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam proved to be the most stable one among these compounds and could be isolated in 55% yield. N-alkyl β-lactams were shown to undergo acidic cleavage leading to the E isomers of 2-(1-ferrocenylmethylidene) malonates as the main products. The structures of the two new compounds, (E)-2-ethoxycarbonyl-3-ferrocenyl-N-((R)-1-phenylethyl)-2-propenamide and trans-N-(tert-butyl)-3-ethoxycarbonyl-4-ferrocenyl-β-lactam were confirmed by X-ray crystallography. The relative thermodynamical stability of the products as well as the energetics of the acid-mediated cleavage of the β-lactam ring was elucidated with DFT calculations.     

1-(1-甲氧基-1-二茂铁基-3-芳基-丙烷-2-基)-1H-1,2,4-三唑类衍生物的合成及生物活性研究

通过在三唑类活性结构中引入较大空间位阻的二茂铁基设计合成了11个新颖的含二茂铁取代的1H-1,2,4-三唑类化合物, 其结构经元素分析, ¹H NMR谱和单晶X-ray衍射分析得到确证. 初步的生物活性测试表明, 部分化合物具有明显的植物生长调节活性.     

Reactions of C(6)F(5)Li with tetracyclone and 3-ferrocenyl-2,4, 5-triphenylcyclopentadienone: An (19)F NMR and X-ray crystallographic study of hindered pentafluorophenyl rotations

Tetracyclone, 2a, reacts with C(6)F(5)Li to yield 2-pentafluorophenyl-2,3,4,5-tetraphenylcyclopent-3-en-1-one, 7, and 5-hydroxy-5-pentafluorophenyl-1,2,3,4-tetraphenylcyclopentadiene, 8, as the result of 1,6 and 1,2 additions, respectively. In contrast, treatment of 3-ferrocenyl-2,4,5-triphenylcyclopentadienone, 2b, with lithiopentafluorobenzene leads to 4-ferrocenyl-4-pentafluorophenyl-2, 3,5-triphenylcyclopent-2-en-1-one, 9, and 5-hydroxy-5-pentafluorophenyl-2-ferrocenyl-1,3, 4-triphenylcyclopentadiene, 10, the products of 1,4 and 1,2 addition, respectively. The structures of 7-9 have been established by X-ray crystallography, and the barriers to rotation (19-21 kcal mol(-)(1)) of the pentafluorophenyl groups in 8-10 have been studied by variable-temperature (19)F NMR. Nucleophilic attack at the ferrocenyl-bearing carbon in 2b is rationalized in terms of a zwitterionic structure in which the positive charge of the "cyclopentadienyl cation" is delocalized onto the iron atom in the organometallic substituent.     

Electrophilic substitutions on some ferrocenyl analgues of chalcones an unusual reaction caused by the high stability of the α-ferrocenylmethyl carbenium ion

Friedel—Crafts acetylation of 5-ferrocenyl-1-phenyl-2,4-pentadie-1-one and 1-ferrocenyl-5-phenyl-1,4-pentadien-3-one has been acomplished. It was found that acetylation takes place on the unsubstituted cyclopentadienyl ring of ferrocene as well as on the double bond of chalcones. In the light of these results the Friedel—Crafts acetylation of 3-ferrocenyl-1-phenyl-2-propen-1-one was reinvestigated and the structures of some drivatives, described earlier, were corrected. The mechanism of the acetylation is discussed briefly.Friedel—Craft alkylation and electrophilic bromination of 3-ferrocenyl-1-phenyl-2-propen-1-one have also been attempted.     

Different rearrangement behaviour of the cation or anion derived from the Diels-Alder adduct of 9-ferrocenylanthracene and 1,4-benzoquinone: ring-opening or paddlewheel formation

Prototropic rearrangement of the Diels-Alder adduct (3a) of 9-ferrocenylanthracene and 1,4-benzoquinone potentially furnishes 9-ferrocenyl-1,4-dihydroxytriptycene (3b) incorporating a C(2v) symmetrical paddlewheel moiety. However, reaction of 3a with HBF(4) unexpectedly yields instead 9-ferrocenyl-10-(2,5-dihydroxyphenyl)anthracene (4) via cleavage of the C9-C12 bond to generate initially a ferrocenyl-stabilized cation. Treatment of 3a with sodium hydride and iodomethane yields 1,4-dimethoxy-9-ferrocenyltriptycene (3c) in high yield but, surprisingly, also leads to fission of the C9-C12 bond resulting, after methylation, in the formation of 9-hydroxy-9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)dihydroanthracene (12), which readily dehydrates on silica to form 9-ferrocenyl-10-(2-hydroxy-5-methoxyphenyl)anthracene (8). The X-ray crystal structures of 3a, 3c and 4 are reported.     

Synthesis of chiral 1-ferrocenylaldols and 1-ferrocenyl-1,3-diols via asymmetric reductions

The asymmetric transfer hydrogenation promoted by the (R,R)-(Ts-DPEN)–Ru complex of some 1-ferrocenyl-1,3-diketones was investigated and in all the cases only the carbonyl group distant to the metallocene moiety was reduced with variable selectivity depending on the C-3 substituent. The CBS-catalyzed reduction of 1-ferrocenyl-β-hydroxy-1-ketones, previously protected as acetates, was also found effective, giving both the corresponding syn- and anti-1,3-diols in satisfactory enantiomeric purity.     

二茂铁基查尔酮衍生物的超快三阶非线性光学响应

合成三例二茂铁基查尔酮衍生物:1-二茂铁基-3-(5-溴噻吩-2-基)-2-丙烯-1-酮(1)、1-二茂铁基-3-(4-溴噻吩-2-基)-2-丙烯-1-酮(2)和1-二茂铁基-3-(5-氯噻吩-2-基)-2-丙烯-1-酮(3);采用1H NMR、13C NMR和HR-MS对化合物1～3进行了结构表征,并测定了其热学性质;运用密度泛函理论方法进行结构优化,并计算得到了它们的分子轨道能量和极化率;采用紫外-可见吸收光谱与Z-扫描技术(532nm,180fs)分别测定了三种化合物的线性和非线性光学性质。结果表明,化合物1～3的紫外吸收波长发生明显红移,且1的非线性吸收幅度、极化率和分子超极化率最大; 1、2和3均存在分子内电荷转移现象,表现出超快三阶非线性光学响应。     

Synthesis and biological activity research of novel ferrocenyl-containing thiazole imine derivatives

A series of novel N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine derivatives were synthesized by condensation of substituted-benzaldehydes with 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole and characterized by ¹H NMR, X-ray diffraction and elemental analysis. The results of bioassay showed that some title compounds exhibited some degree of plant growth regulatory and antifungal activities.