1,8-naphthyridines. Part II. Synthesis of some 3-pyridyl-5,7-di(trifluoromethyl)-1,8-naphthyridin-2(1H)ones

Ethyl 2-amino-4,6-di(trifluoromethyl)nicotinate was prepared and its use as an intermediate in the synthesis of two 3-pyridyl-5,7-di(trifluoromethyr)-1,8-naphthyridin-2(1H)ones is presented. A dimer of 2-amino-4,6-di(trifluoromethyl)nieotinaldehyde is described.     

Trifluoromethyl groups in crystal design of 1,4-diphenyl-1,3-butadienes for topochemical [2 + 2] photodimerization

[structure: see text] UV irradiation of the powdered crystalline sample of each of three (E,E)-1,4-di(trifluoromethyl-substituted)phenyl-1,3-butadienes (1-3) was found to yield a single [2 + 2] cycloaddition product in the solid state. Moreover, upon irradiation, the crystalline samples of two (E,E)-1,4-di(trifluoromethyl- and fluorine-substituted)phenyl-1,3-butadienes (4, 5) undergo a similar conversion to afford a [2 + 2] cycloaddition product, respectively. Our observations suggest that trifluoromethyl groups can be used to direct 1,4-diphenyl-1,3-butadiene molecules to form a parallel, offset-stacked orientation suitable for topochemical [2 + 2] cycloaddition.     

1-(2-Quinoxalyl)-, 1-[3,5-Di(trifluoromethyl)phenyl]-, 1-(2-Carboxyphenyl)-, and 1-Ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydroindazoles

The corresponding 1-(2-quinoxalyl)-, 1-[3,5-di(trifluoromethyl)phenyl]-, and 1-ethoxycarbonyl-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles have been obtained from reactions of 2-acetyl-1,3-cyclohexanedione, its 5,5-dimethyl and 5-(2-furyl) derivatives, with 2-hydrazinoquinoxaline, 3,5-di(trifluoromethyl)phenylhydrazine, and ethoxycarbonylhydrazine. On interaction with ethoxycarbonylhydrazine the intermediate 2-[1-(-ethoxycarbonyl)hydrazino]ethylidene-1,3-cyclohexanediones were also isolated. From the potassium salt of 2-formyldimedone and 2-carboxyphenylhydrazine hydrochloride, 2-(2-carboxyphenyl)hydrazinomethylene-5,5-dimethyl-1,3-cyclohexanedione was obtained, the cyclization of which in ethanol in the presence of HCl led to 1-(2-carboxyphenyl)- and 1-(2-ethoxycarbonylphenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazole.     

Heteroleptic Ruthenium(II) 2,2'-Bipyridine Complexes Incorporating Bipyrazolate and 2-Pyridyl Pyrazolate Ancillaries

Russian Journal of Coordination Chemistry - Treatment of 5,5′-di(trifluoromethyl)-3,3′-bipyrazole (BipzH2) with cis-[RuCl2(Bipy)2]·2H2O (Bipy = 2,2′-bipyridine) or...     

Haloacetylated enol ethers. 2. Synthesis of 5-trifluoromethylpyrazoles

1-Methyl-5-(trifluoromethyl)-1H-pyrazoles 2, 3 and 4,5-dihydro-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-5-ol 4 were prepared by reaction of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones 1 and hydrazine, methylhydrazine, and phenylhydrazine, respectively, in good yields. Compound 1 proved to be a versatile building block for the regiospecific construction of pyrazole rings having an 5-trifluoromethyl substituent.     

A kinetic study of the thermal rearrangement of 2-(trifluoromethyl)-1-vinylcyclopropane

2-(Trifluoromethyl)-1-vinylcyclopropane (6) has been synthesized and its thermal rearrangement investigated. Both the interconversion of the cis and trans isomers of 6 and its irreversible conversion to a mixture of 3- and 4-(trifluoromethyl)cyclopentenes (1:3.9 ratio) proceeded slower than those of any previously reported 2-substituted vinylcyclopropane. It can be concluded that a trifluoromethyl substituent has little if any effect on C---C bond dissociation energies or upon carbon radical stability.     

Cyclization-elimination of 2-phenyldimethylsiloxy-4,6-di(tert-butyl)phenol

A study was carried out on the cyclization-elimination of 2-phenyldimethyl-siloxy-4,6-di(tert-butyl)phenol, which very selectively leads to the formation of benzene and dimethyl [3,5-di(tert-butyl)-o-phenylenedioxy]silicon. This reaction is described by a first-order kinetic equation. The acceleration of the reaction in the presence of organic bases is related to their catalytic action.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2643–2645, November, 1990.     

Copper(I)-catalyzed highly efficient synthesis of benzoselenazoles and benzotellurazoles

A simple and practical useful synthetic method of 1,3-benzoselenazoles having a heteroatom substituent such as NRR', OR, and SR groups at the 2-position was developed by the copper(I)-catalyzed reaction of 2-bromophenyl (1) or 2-iodophenyl (2) isocyanides with selenium and heteroatom nucleophiles. In addition, the synthesis of 2-amino-1,3-benzotellurazoles is also described.     

(t-Bu)2PN=P(i-BuNCH2CH2)3N: new efficient ligand for palladium-catalyzed C-N couplings of aryl and heteroaryl bromides and chlorides and for vinyl bromides at room temperature

By employing Pd(OAc)2, Cs2CO3, or NaOH, and the new ligand (t-Bu)2PN=P(i-BuNCH2CH2)3N (3a), an electronically diverse array of aryl bromides and chlorides possessing base-sensitive substituents (nitro, ester, and keto) provide coupling products with bulky aryl amines in good to excellent yields. Aryl halides possessing other functional groups including cyano, amino, trifluoromethyl, and phenol, coupled with equal ease, producing highly functionalized amines in good to excellent yields. Moreover, an aryl chloro group can be preserved in the presence of a bromo substituent under our reaction conditions. BOC-protected amines also participated efficiently. Heterocyclic bromides and chlorides underwent clean couplings with amines in excellent yields. An important strength of our protocol is the use of lower palladium loadings than those reported earlier, without compromising yields. The air-stable palladium complex (eta3-cinnamyl)PdCl.(3a) (5) was also employed successfully in C-N coupling reactions while the crotyl analogue was less efficacious. The 3a/Pd(OAc)2 catalyst system promotes, for the first time, efficient coupling of vinyl bromides with a variety of amines to produce imines and enamines at room temperature.     

A scalable Nenitzescu synthesis of 2‐methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile

2‐Methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile is a key intermediate in the synthesis of selective androgen receptor modulators discovered in these laboratories. A practical and convergent synthesis of the title compound starting from 4‐nitro‐3‐(trifluoromethyl)phenol and tert‐butyl acetoacetate was developed, including a telescoped procedure for synthesis (without isolation) and Nenitzescu reaction of 2‐trifluoromethyl‐1,4‐benzoquinone. Conversion of the known Nenitzescu indole product to a novel triflate intermediate followed by palladium‐catalyzed cyanation afforded a penultimate carbonitrile. Removal of the C‐3 tert‐butyl ester group on the indole through a decarboxylative pathway completed the synthesis of the title compound in six steps (27% overall yield) from 4‐nitro‐3‐(trifluoromethyl)phenol (five steps, 37% overall yield from tert‐butyl acetoacetate). J. Heterocyclic Chem., (2011).     

Regiocontrolled nitration of di(tert-butyl)phenols

The nitration of 2,4-di(tert-butyl)phenol and 2,6-di(tert-butyl)phenol is accompanied by oxidative processes, leading to products of the oxidative coupling of the starting di(tert-butyl)phenols. On the other hand, the corresponding nitrophenols are formed in quantitative yield in the substitutive nitration of 6-XCH₂- and 4-XCH₂-di(tert-butyl)phenols (X-OH, OR, NR₂).Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2381–2383, October, 1991.     

Synthesis, X-ray structure, and self-assembly of functionalized bis(2,2':6',2' '-terpyridinyl)arenes

meta-Bis(terpyridinyl)phenol has been synthesized from O-benzyl-3,5-di(formyl)phenol in three steps. Its alkylation afforded a series of bisterpyridinylarenes, which can be self-assembled to afford the corresponding hexametallomacrocycles possessing Fe(II), Zn(II), or Ru(II) connectivity. [structure: see text]     

Enantioselective Synthesis of Distorted π-Extended Chiral Triptycenes Consisting of Three Distinct Aromatic Rings by Rhodium-Catalyzed [2+2+2] Cycloaddition

The enantioselective synthesis of distorted π-extended chiral triptycenes, consisting of three distinct aromatic rings, has been achieved with high ee value of 87 % by the cationic rhodium(I)/segphos complex-catalyzed enantioselective [2+2+2] cycloaddition of 2,2′-di(prop-1-yn-1-yl)-5,5′-bis(trifluoromethyl)-1,1′-biphenyl with 6-methoxy-1,2-dihydronaphthalene followed by the diastereoselective Diels–Alder reaction and aromatization. Demethoxy derivatives were also synthesized by the C−O bond cleavage. In this synthesis, the use of the electron-deficient diyne and the electron-rich alkene is crucial to suppress the undesired strain-relieving carbocation rearrangement and stabilize the distorted triptycene structure.     

含三氟甲基和双希夫碱化合物的合成与表征

利用1,4-双(4-氨基-2-三氟甲基苯氧基)苯与苯甲醛或其衍生物的反应,合成了一系列含三氟甲基和双希夫碱的新化合物,其结构经UV,1HNMR,IR和元素分析表征。     

Crystal structure of 4,4-bipyridine-containing complexes of copper(II) nitrate with 1-[(2-Hydroxyethylimino)methyl]naphthalen-2-ol and 2-[(2-hydroxyethylimino)methyl]phenol

The crystal structures of (μ-4,4-bipyridine)-di(nitrato-1-[(2-hydroxyethylimino)methyl]naphthalen-2-olocopper (I) and catena-di(μ-4,4’-bipyridine)di(μ-4,4’-bipyridine)-di(nitrato-2-[2-(hydroxyethylimino) methyl]phenolocopper)diaquacopper(II) nitrate (II) were determined. In the crystal of I, each of the two copper atoms coordinates a singly deprotonated tridentate azomethine molecule, a nitrate ion, and bipyridine, which functions as a bridge between the central atoms. The copper coordination polyhedron is a slightly distorted tetragonal pyramid with the base formed by the imine and bipyridine nitrogen atoms and the phenol and alcohol oxygen atoms. The axial site in the pyramid is occupied by the oxygen atom of the monodentate nitrate groups. In the trinuclear structure II with C₂ crystal chemical symmetry, the terminal coordination unit is composed through copper coordination of monodeprotonated 2-[2-(hydroxyethylimino)methyl]phenol, bipyridine, and the nitrate anion. In the crystal, the trinuclear molecules form infinite ribbons along the z axis in which the pyridine molecules perform the bridging function. The central copper atom has an octahedral configuration formed by the nitrogen atoms of four 4,4’-bipyridine molecules and oxygen of two water molecules.     

Hexafluoroacetone as protecting and activating reagent: reactions of hexafluoroacetone with α-keto acids

Hexafluoroacetone and α-keto acids react to give 5,5-bis(trifluoromethyl) substituted 2(5H)-furanones and/or 2,2-bis(trifluoromethyl)-1,3-dioxolan-4-ones depending upon the substituent pattern of the side chain of the acid. A fluoroanalogue of the natural product zymonic acid was obtained from ethyl 3,3,3-trifluoropyruvate and 2-oxosuccinic acid in one step.     

Heteroatom influence in substituted benzenes and pyridine-like heterocycles in terms of direct and indirect intramolecular interactions

The general expression for the one-electron density matrix obtained previously for saturated organic molecules (V. Gineityte, J. Mol. Struct. (Theochem), 343 (1995) 183) is shown to be applicable also to substituted benzenes and pyridine-like heterocycles. On this basis, a new interpretation of the influence of a heteroatom (substituent) upon the remaining fragment of an aromatic molecule is suggested. To this end, the occupation number of a 2p_z AO of the aromatic ring has been expressed as a sum of five terms, two of them describing the intramolecular charge transfer and the remaining ones representing the secondary (induced) dipole moments arising within the ring under the influence of heteroatom, viz. the so-called ipso–ortho (para–meta), para–ipso and ortho–meta dipole moments. Just the latter two moments proved to play the principal role in the formation of the observed picture of the electron density distribution, viz. of an increase (reduction) of occupation numbers of 2p_z AOs in the ortho and para positions after introducing an electron-donating (accepting) substituent. For pyridine-like heterocycles and substituted benzenes, these dipole moments are determined mostly by the direct and the indirect interactions, respectively, between the highest occupied and the lowest vacant MO of benzene. Orbitals of the heteroatom (substituent) play the role of mediators in the above-mentioned indirect interaction.     

Preparation of (E)-1-aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propenes via stereoselective bissilylation of trifluoromethyl aryl acetylenes and electrophilic substitution of its TMS groups

Preparations and reactions of (E)-1-aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propenes are described. (E)-1-Aryl-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-propene was prepared from aryl trifluoromethyl acetylenes via reductive bissilylation by TMSCl/Mg in good yields. The silyl groups of (E)-3,3,3-trifluoro-1,2-di(trimethylsilyl)-1-phenyl-1-propene were substituted by electrophiles in both a stepwise and stereoselective (and/or stereospecific) manner. This compound could be a building block for preparations of substituted trifluoropropenes.     

Cyclobutene Formation in PtCl2‐Catalyzed Cycloisomerizations of Heteroatom‐Tethered 1,6‐Enynes

Aza(oxa)bicyclo[3.2.0]heptenes are accessed through the PtCl₂‐catalyzed cycloisomerizations of heteroatom‐tethered 1,6‐enynes featuring a terminal alkyne and amide as the solvent. It is shown that the weak coordinating properties of the solvent and alkyl substituent(s) at the propargylic carbon atom favor the formation of cyclobutenes instead of other possible cycloisomerization products such as 1,3‐diene derivatives or cyclopropane‐fused heterocycles.     

Development of highly regioselective amidyl radical cyclization based on lone pair-lone pair repulsion

The substituent effect on the reactivity and regioselectivity of N-(4-pentenyl)amidyl radical cyclization was investigated. Exclusive 6- endo cyclization was observed for N-(4-pentenyl)amidyl radicals with internal vinylic heteroatom substitution (Cl, Br, I, OMe, SEt). The substituent on the carbonyl group also showed a significant influence on the reactivity of amidyl radicals, which increases in the order of Ph < Me < OEt. As a result, the photostimulated reactions of N-(4-halopent-4-enyl)amides and carbamates (X = Cl, Br, I) with DIB/I 2 or Pb(OAc) 4/I 2 led to the efficient and exclusive formation of the corresponding piperidines while those of N-(5-halopent-4-enyl)amides afforded the pyrrolidine products only. The halogen-substitution effect also allowed the 6- exo and 7- endo amidyl radical cyclization to proceed in a highly regioselective manner. The above experimental results, in combination with theoretical analyses, revealed that the lone pair-lone pair repulsion between the nitrogen radical and the vinylic heteroatom played an important role in controlling the regioselectivity of cyclization.