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At least 937 records · Page 52Linked to original sources
PubMed2001

Selective halogen-magnesium exchange reaction via organomagnesium ate complex.

Halogen-magnesium exchange of various aryl halides is achieved with a magnesium ate complex at low temperatures. Tributylmagnesate (nBu3MgLi) induces facile iodine-magnesium exchange at -78 degrees C. Dibutylisopropylmagnesate (iPr(n)Bu2MgLi) is more reactive than nBu3MgLi, and this reagent accomplishes selective bromine-magnesium exchange at -78 degrees C. This procedure is utilized for the preparation of various polyfunctionalized arylmagnesium species. The exchange of alkenyl halides using this method proceeds with retention of configuration of the double bond.

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PubMed2001

Synthesis of a muscarinic receptor antagonist via a diastereoselective Michael reaction, selective deoxyfluorination and aromatic metal-halogen exchange reaction.

An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.

Amides↗
PubMed2002

Is an iodine atom almighty as a leaving group for Bu(3)SnH-mediated radical cyclization? The effect of a halogen atom on the 5-endo-trig radical cyclization of N-vinyl-alpha-halo amides.

The effect of a halogen atom as a leaving group on Bu(3)SnH-mediated 5-endo-trig radical cyclization of N-(cyclohex-1-enyl) alpha-halo amides was examined. The cyclization of alpha-chloro amides occurred with a high degree of efficiency, whereas the corresponding alpha-iodo congeners gave only limited quantities of cyclization products. A detailed study revealed that these phenomena could be attributed to the initial conformations of alpha-halo amides. The cyclizing ability of alpha-iodo amides can be restored with Bu(3)SnCl or Bu(3)SnF as an additive. The cyclization of an alpha-iodo amide in the presence of Bu(3)SnF could be applied to a short-step synthesis of lycoranes featuring sequential 5-endo-trig and 6-endo-trig radical cyclizations.

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PubMed2002

Halogen derivatives of m-phenylene(carbeno)nitrene: a switch in ground-state multiplicity.

m-Phenylene-coupled carbenonitrenes [(3-nitrenophenyl)methylene (2-H), (3-nitrenophenyl)fluoromethylene (2-F), (3-nitrenophenyl)chloromethylene (2-Cl), (3-nitrenophenyl)bromomethylene (2-Br)] have been investigated computationally (with B3LYP, MCSCF, CASPT2, ROMP2, and QCISD(T) methods) and experimentally (with IR, UV, and ESR spectroscopy). For each species, five electronic states were considered. At the highest level of theory explored, the parent compound (2-H) has a quintet ground state, but its halogen derivatives (2-X, X = F, Cl, and Br) have triplet ground states. A linear relationship between the Q[bond]T energy gap of 2-X and the T-S gap of the corresponding phenylcarbenes 8-X is found, which can be helpful in rationalizing and predicting ground-state multiplicities in m-phenylene-linked carbenonitrenes and similar species. Precursors for the photochemical generation of 2-X (X = H, F, Cl, and Br) were synthesized and photolyzed in matrixes (Ar, triacetin) at low temperatures. IR (Ar, 13 K) and ESR (triacetin, 77 K) data are compatible with the generation of triplet halocarbenonitrenes 2-X, (X = F, Cl, and Br). All four compounds upon further irradiation undergo isomerization to substituted cyclopropenes 5-X (X = H, F, Cl, and Br), as suggested by their IR spectra.

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PubMed2005

An experimental and computational investigation of the Diels-Alder cycloadditions of halogen-substituted 2(H)-pyran-2-ones.

[reaction: see text] Diels-Alder reactions of 3- and 5-halo-subsituted 2(H)-pyran-2-ones with both electron-rich and electron-deficient dienophiles afford stable and readily isolable bridged bicyclic lactone cycloadducts. These cycloadditions proceed with excellent regioselectivity and very good stereoselectivity. In contrast, Diels-Alder reactions of 4-halo-subsituted 2(H)-pyran-2-ones afford cycloadducts which are very prone to loss of bridging CO(2) and the subsequent formation of barrelenes ([2.2.2]cyclooctenes). Furthermore, these cycloadditions proceed with only moderate regio- and stereoselectivity. For both series of the 3- and 5-halo-subsituted 2(H)-pyran-2-ones and 4-halo-subsituted 2(H)-pyran-2-ones, the reactivity patterns do not significantly change between the halogens. The regio- and stereochemical preferences of the cycloadditions of halo-substituted 2(H)-pyran-2-ones are investigated computationally. Calculations were carried out on the transition states leading to the four possible regio- and stereoisomeric cycloadducts by using density functional theory (B3LYP/6-31G). These studies allow prediction of the regio- and stereoselectivity in these reactions which are broadly in line with experimental observations.

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PubMed2005

Investigations of the halogen dance reaction on N-substituted 2-thiazolamines.

The halogen dance (HD) reaction on various 2-thiazolamine systems was investigated providing an easy access to a series of 5-substituted 4-bromo-2-thiazolamine derivatives. We could show that HD is a very favored process for the investigated systems and that prevention of HD is only possible when optimized reaction conditions and selected electrophiles are applied.

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PubMed2004

Syntheses of very dense halogenated liquids.

A family of halogenated liquids with densities ranging from 1.95 to 2.80 g cm(-3) was readily synthesized by a one-pot procedure. These liquids exhibit characteristics of ionic liquids with melting/transition points lower than room temperature, long liquid ranges, and marked hydrolytic and thermal stabilities.

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PubMed2006

Halogenated 2'-chlorobithiazoles via Pd-catalyzed cross-coupling reactions.

Halogenated bithiazoles allow facile further functionalization and are, therefore, suitable intermediates for the synthesis of compounds with interesting biological activity or material science properties. The applicability of three coupling methods (Negishi, Suzuki, and Stille) for the synthesis of the title compounds was compared. The Negishi method proved to be troublesome, and side reactions were predominant. The synthesis of the first thiazoleboronic acid ester offered a new method for the formation of bithiazoles, not generally applicable so far. The lower toxicity compared to that of tin organyls make this method an approach with interesting perspectives. The Stille coupling proved to be superior to the other methods and enabled the synthesis of the title compounds with diverse connectivity.

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PubMed1998

Regiospecific Vinyl Phosphate/beta-Keto Phosphonate Rearrangements Initiated by Halogen-Metal Exchange.

A new strategy has been developed for preparation of beta-keto phosphonates via a halogen-metal exchange induced 1,3-phosphorus migration of 2-bromovinyl phosphates. These intermediates can be prepared through conversion of an alpha-bromo ketone to the appropriate enolate by reaction with strong base, or through conjugate addition to an alpha-bromo alpha,beta-unsaturated ketone. In either case, trapping the resulting enolate by reaction with a dialkyl phosphorochloridate gives the 2-bromovinyl phosphate. Metalation can be accomplished upon treatment with n-BuLi, and rearrangement is facile once metalation has been achieved. Studies with isotopically labeled substrates have shown that this rearrangement is regiospecific, in contrast to vinyl phosphate/beta-keto phosphonate rearrangements induced by strong base where regioisomeric products are sometimes obtained.

Journal Article↗
PubMed2005

Halogens in competition: electronic structure of mixed dihalobenzenes.

The electronic structure of all isomeric dihalobenzenes C6H4XY (X, Y = Cl, Br, I) has been investigated by HeI/HeII photoelectron spectroscopy, Green's functions calculations, and comparison with the spectra of related dihalobenzenes C6H4X2 (X = Cl, Br, I). The careful analysis of measured pi orbital and halogen lone pair ionization energies enabled us to describe substituent effects in terms of resonance, inductive, steric, and spin-orbit coupling interactions.

Journal Article↗
PubMed2005

Length and substituent-scrambling energies of parent and halogen-substituted conjugated polyynes.

Conjugated polyynes are a class of species of diverse and increasing interest. Length-scrambling and substituent scrambling reaction energies were examined using ab initio quantum chemistry calculations to investigate issues concerning the energetic effects of the molecular ends (substituent communication). Computations were performed for the parent, monohalogenated, and dihalogenated (F, Cl, Br, I) polyynes of up to 60 carbon atoms. A study of resonance effects using natural resonance theory and bond lengths demonstrates lone-pair-donating effects that increase in the series F < Cl < Br < I, but run counter to the halogen inductive effects which decrease in this series and dominate energetic effects.

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PubMed2006

Properties of the halogen-hydride interaction: an ab initio and "atoms in molecules" analysis.

X-Cl...H-Y interactions are analyzed by applying ab initio methods as well as the Bader theory. All calculations were performed using Pople's basis sets (6-311++G(2df,2pd) and 6-311++G(3df,3pd)) as well as the Dunning-type bases (aug-cc-pVDZ and aug-cc-pVTZ) within the MP2 method. For the complexes analyzed here, X-Cl and H-Y may be treated as a Lewis acid and a Lewis base, respectively. The Cl...H interactions are rather weak or at most moderate since, for the strongest interaction of the F3...HLi complex, the binding energy calculated at the MP2/6-311++G(3df,3pd) level of approximation amounts to -3.4 kcal/mol, and the H...Cl distance is equal to 2.65 A, less than the corresponding sum of van der Waals radii. These interactions may be classified as halogen-hydride interactions. However, some of the complexes analyzed, especially F3SiCl...HBeF and F3SiCl...HBeF, are very weakly bound, probably by typical van der Waals interactions.

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PubMed2004

Reactions of halobenzenes with methanol on the microporous solid acids hbeta, HZSM-5, and HSAPO-5: halogenation does not improve the hydrocarbon pool.

The reactions of fluorobenzene, 3-fluorotoluene, and three isomers of difluorotoluene, chlorobenzene, and bromobenzene with excesses of methanol were investigated on the large-pore catalysts HBeta (*BEA) and HSAPO-5 (AFI), and on the medium-pore HZSM-5 (MFI). Flow reactor studies in pulse mode with GC-MS detection revealed that the fluorobenzene derivatives were readily methylated at, for example, 375 degrees C, but not even pentamethylfluorobenzene was obviously active as a reaction center for methanol-to-olefin (MTO) catalysis. Carbon-labeling studies revealed that small amounts of methylbenzenes were formed by defluorination, and these aromatic hydrocarbons seemed to account for the small yields of olefins (and their secondary reaction products) observed. Loss of one fluorine was also evident in the products for one of the difluorotoluene isomers. On HSAPO-5 the activity order for ring-methylation of halobenzenes was F > Cl >> Br. On HZSM-5, chlorobenzene and especially bromobenzene lost halogen through a route forming halomethane. These largely negative results will nevertheless be useful in testing theoretical models of the detailed reaction steps in the hydrocarbon pool mechanism for MTO catalysis.

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PubMed2006

Influence of halogen substituents on the self-assembly of oligothiophenes--a combined STM and theoretical approach.

Iodinated quaterthiophenes 2-3 have been synthesized and their self-assembling behavior investigated at the liquid-solid interface by means of high-resolution scanning tunneling microscopy in comparison to parent oligothiophene 1. All three compounds spontaneously give well-ordered 2D crystalline monolayers at the graphite surface and order in a lamella-type arrangement of the conjugated backbones concomitant with an interlocking of the alkyl side chains. Symmetrically substituted oligothiophenes 1 and 3 without a relevant dipole moment self-assemble in a similar fashion, exhibiting comparable unit cells, whereas monoiodo derivative 2 arranges as pairs along the lamella axis due to the presence of a permanent dipole moment induced by the polarizable halogen group. Corroborated by quantum chemical calculations, novel head-to-head (iodo-iodo) intermolecular interactions were found to take place for this unsymmetrical derivative. The investigation of mixed solutions clearly reveals that at the solid-liquid interface a homogeneous layer of this compound is formed, which comprises the highest packing density leading to a separation process at the interface.

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PubMed2002

Halogenated metabolites from the new Okinawan red alga Laurencia yonaguniensis.

A novel brominated diterpene based on the rare neoirieane skeleton, named neoirietetraol (1), has been isolated along with a halogenated C15 acetogenin, (3Z)-laurenyne (2), from a new Laurencia species, L.yonaguniensis Masuda et Abe, species inedita, collected at Yonaguni Island, Okinawa Prefecture, Japan. The structures of these metabolites were elucidated by spectroscopic data (IR, 1H NMR, 13C NMR, 2D NMR, and MS). Neoirietetraol (1) was toxic to the brine shrimp (Altemia salina; LC50, 40.1 microM) and also showed weak antibacterial activities against two marine bacteria, Alcaligenes aquamarinus and Escherichia coli.

Alcaligenes↗
PubMed2005

Halogenated helianane derivatives from the sponge Spirastrella hartmani.

Two new halogenated derivatives (1 and 2) of helianane (3) were isolated from the 2-propanol extract of the sponge Spirastrella hartmani. The structures of the new derivatives were determined on the basis of detailed spectroscopic analysis, including (+)-HREIMS and 1D and 2D NMR. Compound 1 showed in vitro cytotoxicity against the human tumor cell lines A549, HT29, and MDA-MB-231.

Animals↗
PubMed1999

Nonhalogenated and halogenated phlorotannins from the brown alga carpophyllum angustifolium

Using HPLC, forty-five phloroglucinol derivatives were obtained from an ethanolic extract of the brown alga Carpophyllum angustifolium after peracetylation. Compounds of the fuhalol-B series are described. The structure of hydroxyheptafuhalol-B nonadecaacetate is confirmed by the addition of (13)C NMR spectral data, octafuhalol-C heneicosaacetate is described for the first time. The occurrence of four halogenated phlorotannins is reported: 2-chlorophloroglucinol triacetate, 2[D']iododiphlorethol pentaacetate, which had been isolated formerly only as a mixture, 3[A]chlorobifuhalol hexaacetate, and 3[A(4)]chlorodifucol hexaacetate. All substances were characterized by means of spectral analysis.

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