Addition Of Heteroatoms Research Articles

JIRO TSUJI. Palladium reagents and catalysts: new perspectives for the 21st century. Wiley–VCH, 2004. 670 pp. ISBN 0470850337 (paperback)

JIRO TSUJI. Palladium reagents and catalysts: new perspectives for the 21st century. Wiley–VCH, 2004. 670 pp. ISBN 0470850337 (paperback)

Structure–activity relationships of piperazinebenzylamines as potent and selective agonists of the human melanocortin-4 receptor

SAR studies on a series of piperazinebenzenes directed toward the human melanocortin-4 receptor resulted in potent MC4R agonists. Replacement of the triazole moiety of an initial lead 4 by a basic nitrogen baring a lipophilic side-chain increased the binding affinities of these compounds. Analogs bearing an additional hetero-atom in the side-chain possessed good agonist potency. Thus, 11h had a K i of 11 nM, and 13g exhibited an EC 50 of 3.8 nM and a K i of 6.4 nM.

Highly Diastereoselective Radical Addition to Glyoxylate Imines of Chiral Amines without Additional Heteroatoms.

AbstractFor Abstract see ChemInform Abstract in Full Text.

4-(omega-(alkyloxy)alkyl)-1H-imidazole derivatives as histamine H(3) receptor antagonists/agonists.

In an effort to develop new histamine H(3) receptor antagonists usable as pharmacological tools we present here novel unsymmetrical ether derivatives. Etherification of different omega-(1H-imidazol-4-yl)alkyl scaffolds led to compounds containing alkyl chains of increasing lengths either with or without unsaturated termini, cycloalkyl or arylalkyl moieties, or additional heteroatoms. When investigated in an in vitro assay on rat synaptosomes, the majority of compounds displayed potencies in the low nanomolar concentration range at the H(3) receptor, e.g., 4-(3-(3-cyclopentylpropyloxy)propyl)-1H-imidazole (27, K(i) = 7 nM). FUB 465, 4-(3-(ethoxy)propyl)-1H-imidazole (14), a useful tool for the characterization of constitutive activity of H(3) receptors in vivo in rodents, proved to be of high oral in vivo potency in mice (ED(50) = 0.26 mg/kg). Further, the influence of chosen compounds on specific [(35)S]GTPgammaS binding was assayed on HEK293 cell membranes expressing the human histamine H(3) receptor revealing partial agonism of the compounds in this particular model. These distinct responses are further hints for "protean agonism" in this class of compounds. Additionally, selected compounds were functionally investigated in vitro on isolated organs of the guinea-pig at H(3), H(1), and H(2) receptors.

Highly diastereoselective radical addition to glyoxylate imines of chiral amines without additional heteroatoms

The diastereoselective addition of alkyl radicals to glyoxylate imines of α-alkylbenzylamines has been investigated and it was found that diastereoselectivity improved as the size of the alkyl group increased.

Synthesis, CD Spectra, and Enzymatic Stability of β2‐Oligoazapeptides Prepared from (S)‐2‐Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu

Abstractβ‐Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs. 1 and 2). We report here the synthesis and spectroscopic investigations of β2‐peptide analogs consisting of (S)‐3‐aza‐β‐amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N‐benzyl‐L‐α‐amino acids with an oxaziridine (Scheme 1). Couplings and fragment coupling of the 3‐benzylaza‐β2‐amino acids and a corresponding tripeptide (N‐Boc/C‐OMe strategy) with common peptide‐coupling reagents in solution led to β2‐di, β2‐tri‐, and β2‐hexaazapeptide derivatives, which could be N‐debenzylated (4–9; Schemes 2–4). The new compounds were identified by optical rotation, and IR, 1H‐ and 13C‐NMR, and CD spectroscopy (Figs. 4 and 5) and high‐resolution mass spectrometry, and, in one case, by X‐ray crystallography (Fig. 3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of the β2‐azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N‐Boc and C‐OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)‐314‐helical structure. The N‐Boc‐β2‐tri and N‐Boc‐β2‐hexaazapeptide esters, 7 and 9, were shown to be stable for 48 h against the following peptidases: pronase, proteinase K, chymotrypsin, trypsin, carboxypeptidase A, and 20S proteasome.

Synthesis and structure-activity relationships of amide and hydrazide analogues of the cannabinoid CB(1) receptor antagonist N-(piperidinyl)- 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716).

Analogues of the biaryl pyrazole N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716; 5) were synthesized to investigate the structure-activity relationship (SAR) of the aminopiperidine region. The structural modifications include the substitution of alkyl hydrazines, amines, and hydroxyalkylamines of varying lengths for the aminopiperidinyl moiety. Proximity and steric requirements at the aminopiperidine region were probed by the synthesis of analogues that substitute alkyl hydrazines of increasing chain length and branching. The corresponding amide analogues were compared to the hydrazides to determine the effect of the second nitrogen on receptor binding affinity. The N-cyclohexyl amide 14 represents a direct methine for nitrogen substitution for 5, reducing the potential for heteroatom interaction, while the morpholino analogue 15 adds the potential for an additional heteroatom interaction. The series of hydroxyalkyl amides of increasing chain length was synthesized to investigate the existence of additional receptor hydrogen binding sites. In displacement assays using the cannabinoid agonist [(3)H](1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl) cyclohexan-1-ol (CP 55 940; 2) or the antagonist [(3)H]5, 14 exhibited the highest CB(1) affinity. In general, increasing the length and bulk of the substituent was associated with increased receptor affinity and efficacy (as measured in a guanosine 5'-triphosphate-gamma-[(35)S] assay). However, in most instances, receptor affinity and efficacy increases were no longer observed after a certain chain length was reached. A quantitative SAR study was carried out to characterize the pharmacophoric requirements of the aminopiperidine region. This model indicates that ligands that exceed 3 A in length would have reduced potency and affinity with respect to 5 and that substituents with a positive charge density in the aminopiperidine region would be predicted to possess increased pharmacological activity.

Science of Synthesis: Houben−Weyl Methods of Molecular Transformations. Volume 11. Hetarenes and Related Ring Systems: Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom Volume Editor: Ernst Schaumann (Clausthal-Zellerfeld, Germany). Georg Thieme Verlag: Stuttgart and New York. 2002. lii + 1160 pp. $1740.00. ISBN 3-13-112261-7.

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTScience of Synthesis: Houben−Weyl Methods of Molecular Transformations. Volume 11. Hetarenes and Related Ring Systems: Five-Membered Hetarenes with One Chalcogen and One Additional Heteroatom Volume Editor: Ernst Schaumann (Clausthal-Zellerfeld, Germany). Georg Thieme Verlag: Stuttgart and New York. 2002. lii + 1160 pp. $1740.00. ISBN 3-13-112261-7.Cite this: J. Am. Chem. Soc. 2002, 124, 26, 7874Publication Date (Web):March 20, 2002Publication History Published online20 March 2002Published inissue 1 July 2002https://doi.org/10.1021/ja025223zCopyright © 2002 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views169Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (33 KB) Get e-AlertsSUBJECTS:Group 16 compounds,Reaction products Get e-Alerts

Complexes of Some d and f Elements with New 4-Acylpyrazol-5-ones: Synthesis and Study

Complexes of 1-phenyl-3-methyl-4-thenoylpyrazol-5-one and of 1-phenyl-3-methyl-4-furancarbonylpyrazol-5-one, which was synthesized for the first time, with copper, rhodium, lanthanum, and europium were studied. The substances obtained were studied using elemental analysis and IR spectroscopy, while the rhodium derivatives were additionally studied using the 1H NMR method. The thermal stability of the copper derivatives was studied upon heating in a vacuum. The presence of additional heteroatoms in acylpyrazolone had virtually no effect on the structure and composition of the complexes formed. These ligands were shown to coordinate atoms of d and f metals through oxygen atoms similarly to other β-diketones, whereas the remaining heteroatoms only participated in the formation of a hydrogen bonding system with additional ligands or coordinated solvent molecules.

Photochemistry of 1,1-dicyano-1-alkenes: General aspects

The chemical behaviour of 32 selected 1,1-dicyano-1-alkenes (DCNA) that are devoid of additional unsaturation and of additional hetero-atoms, upon direct excitation by continuous irradiation with light of 253.7 nm wavelength into the long-wavelength flank of their longest wavelength UV absorption band has been studied in solvents ranging from cyclohexane to methanol. The predominant reaction products in the majority of cases were 1,1-dicyano-cyclopropanes formed via 1,2-migration of either hydrogen or methyl/alkyl from C-3 to C-2 (olefin to cyclopropane photorearrangement, OCPR). Photoreactions competing with OCPR were hydrogen atom abstraction from solvent by the C-2 of the DCNA and, in characteristically favourable cases only, 3,4-CC bond cleavage. In cases of low OCPR quantum yields, hydrogen abstraction from solvent was dominant in cyclohexane or methanol but it could be suppressed by the choice of a solvent (methylene chloride, acetonitrile, tert-butanol) that more strongly resisted hydrogen abstraction. Further minor by-products were isomeric DCNA and 1,1-dicyano-3-alkenes. No carbene-derived products were observed. Supplementary experiments included quenching experiments and an investigation of the DCNA triplet state. The DCNA triplet state was formed at only ca. 1% on direct irradiation but it could be efficiently produced by sensitisation with benzophenone; in the absence of olefins as inter- or intramolecular substrates, it was fairly unreactive. All observed reactions occur from the lowest excited DCNA singlet state. According to the quenching experiments, this state is short-lived as compared to diffusional movements. Other than OCPR which appears to be due to cationic reactivity at C-2 exhibited by the perpendicular geometry of the excited double bond, hydrogen abstraction and 3,4-CC bond cleavage appear to be due to radical reactivity at C-2 exhibited by geometries of the excited double bond that are intermediate between planar and perpendicular and are due to vibration about the perpendicular conformation.

Photoelectron spectroscopy of bimetallic aluminum cobalt cluster anions: Comparison of electronic structure and hydrogen chemisorption rates

The photoelectron spectra of small mass-selected aluminum-rich AlnCo− (n=8–17) and cobalt-rich ConAlm− clusters (n=6,8,10; m=1,2) are measured at photon energies of 3.49 eV with the aid of a magnetic bottle photoelectron spectrometer. The electronic structures of the bimetallic clusters are compared with those of pure Aln− and Con− clusters, which are measured under the same conditions. The threshold behavior (electron affinities and vertical detachment energies) is analyzed, and the application of the electronic shell model reveals a similar shell structure of Co-doped Al clusters with a single heteroatom. Additional heteroatom doping induces shell perturbations. Compared to pure Aln clusters, single-atom doped clusters show a hybridization of Al s, p and Co d orbitals resulting in a merging of spectral features at low binding energies. The evolution of the electronic structure is compared with reported ionization potentials [Menezes and Knickelbein, Chem. Phys. Lett. 183, 357 (1991); Z. Phys. D 26, 322 (1993)]. The hydrogen chemisorption behavior of neutral aluminum cobalt clusters [Nonose et al., Chem. Phys. Lett. 164, 427 (1989)] shows a clear influence of Co d states at low binding energies in the case of AlnCo, whereas for ConAlm clusters (n>m) the geometric effect becomes more dominant.

Effect of Ring Size or an Additional Heteroatom on the Potency and Selectivity of Bicyclic Benzylamine-Type Inhibitors of PhenylethanolamineN-Methyltransferase1a

In the search for potent and selective inhibitors of the enzyme phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28), we examined the effect of ring size or an additional heteroatom in the conformationally-restricted benzylamine-type PNMT inhibitors. Based on semiempirical calculations (MNDO) and molecular modeling studies, PNMT-inhibitory activity of these compounds seemed to be dependent on (a) the torsion angle between the plane of the aromatic ring and the endo N atom lone pair ( tau 2 angle), with the optimal value of tau 2 being about - 75 degrees, and (b) the amount of steric bulk about the 3-position of 1,2,3,4-tetrahydroisoquinoline (5, THIQ). 2,3,4,5-Tetrahydro-1H-2-benzazepine (6) was found to have the highest selectivity (PNMT Ki = 3.34 microM, alpha 2 Ki = 11 microM, selectivity = 3.2) as compared to other homologues of THIQ (PNMT Ki = 9.67 microM, alpha 2 Ki = 0.35 microM, selectivity = 0.036). The higher PNMT-inhibitory activity of 6 was attributed to favorable steric interactions of the puckered methylene groups in the putative bioactive conformation of 6 at the PNMT active site, whereas unfavorable interactions of these puckered methylene groups at the alpha 2-adrenoceptor were thought to be the cause of reduced alpha 2 affinity of 6. No further enhancement of the selectivity of the benzazepine ring system could be obtained via introduction of a second heteroatom (N, O, S) at the 5-position in this ring system.

Tetraheterafulvalenes as Precursors of Conducting Materials

ABSTRACTMethods for preparation of thetraheterafulvalenes containig O, S, Se, N as additional he-teroatoms and some of their conducting products are described. Also, results concerning stoichi-ometry, structures, and physical properteis are briefly discussed.

Induced nucleation of diamond powder

The effects of heteroatom addition on the nucleation of solid carbon in a low-pressure plasma reactor were investigated. Silane or diborane were added to acetylene mixed in hydrogen or argon. Oxygen was added to some of the diborane containing gas mixtures. Silane containing mixtures resulted in powder comprised of weakly bonded amorphous hydrogenated carbon-silicon material. The addition of diborane resulted in substantial production of diamond particles, 5 to 450 nm in diameter, under the conditions that show no diamond formation without diborane present. The observed yield of the oxidation-resistant powder produced in boron-containing mixtures reached 1.3 mg/h with the linear growth rates of diamond particles on the order of 102–104 μm/h. Implication of these results to interstellar dust formation is discussed.

Some unsymmetrical polyheterotetraheterafulvalenes and their conducting salts

The synthesis and properties of some unsymmetrical tetraheterafulvalenes, containing O, S, Se, N as additional heteroatoms, are described. Also, results on the crystal structure and physical properties of a number of conducting salts based on these compounds are briefly discussed.

New P,N-Cyclic Ligands

Abstract The anions of P,N-cyclic metaphosphimic acids (MPmn-, n = =3, 4…) interact with cations as conformationally labile multidentate ligands. They belong to the cyclophosphazane class and can be obtained from chloroderivatives (NPCl2)n associated with a related class of P,N-compounds (cyclophosphazenes. Besides halogens, a great variety of organic radicals can act as substituents in the cyclophospnazenes. An additional introduction of donating atoms or groups in these radicals results in new multidentate ligands. Like the MPmn- they demonstrate a cation binding ability. Thus P,N-cyclic ligands can contain endocyclic functional groups POO- which are inherent to common MPmn- or various exo-cyclic groups, e.g. -COO−, -PR2O−, -PROO−, -NR2etc., linked to the cycle via side chains. Furthermore, miscellaneous phosphazane-phosphazene structures as well as those with an additional heteroatom can be designed. We have obtained the first examples of P,N-cyclic chelantes of some structural types. These are bicycles based on MPmn- cross-linked by organic bridges. Such ligands can take a sandwich configuration. Neutral and acido-ligands of cyclo-pendante type involving groups -COO−, -PPh2O and >O as well as a ligand with endocyclic sulfur have been obtained too. Selective or universal chelantes, extragents, coloured ligands and other reagents can be synthesized depending on a ligand structure design, the nature of organic fragments linked to the cycle and the type of functional groups.

New P,N-Cyclic Ligands

Abstract The anions of P,N-cyclic metaphosphimic acids (MPmn-, n = =3, 4…) interact with cations as conformationally labile multidentate ligands. They belong to the cyclophosphazane class and can be obtained from chloroderivatives (NPCl2)n associated with a related class of P,N-compounds (cyclophosphazenes. Besides halogens, a great variety of organic radicals can act as substituents in the cyclophospnazenes. An additional introduction of donating atoms or groups in these radicals results in new multidentate ligands. Like the MPmn- they demonstrate a cation binding ability. Thus P,N-cyclic ligands can contain endocyclic functional groups POO- which are inherent to common MPmn- or various exo-cyclic groups, e.g. -COO−, -PR2O−, -PROO−, -NR2etc., linked to the cycle via side chains. Furthermore, miscellaneous phosphazane-phosphazene structures as well as those with an additional heteroatom can be designed. We have obtained the first examples of P,N-cyclic chelantes of some structural types. These are bicycles based on MPmn- cross-linked by organic bridges. Such ligands can take a sandwich configuration. Neutral and acido-ligands of cyclo-pendante type involving groups -COO−, -PPh2O and >O as well as a ligand with endocyclic sulfur have been obtained too. Selective or universal chelantes, extragents, coloured ligands and other reagents can be synthesized depending on a ligand structure design, the nature of organic fragments linked to the cycle and the type of functional groups.

Asymmetric conjugate addition reactions with Chiral Amidocuprates: The effect of Cu(I) salts and coordinating heteroatoms

Chiral amidocuprates with methyl or n -butyl transferable ligands containing additional heteroatoms afforded higher asymmetric induction with CuBr than with CuI, although reactivity and chemical yields are generally higher with CuI. The enantiomeric excess generally increases with the number of heteroatoms in the chiral amine ligand available for coordination and was low and extremely variable for the bidentate system 1a.

Anwendungsbreite der reduktiven Kupplung aromatischer Aldimin‐Derivate mit niedervalenten Titan‐Reagenzien zu 1,2‐Diarylethylendiaminen

Scope and Limitations of the Reductive Coupling of Aromatic Aldimine Derivatives with Formation of 1,2‐Diarylethylenediamine Units, Using Low‐Valent Titanium ReagentsBesides the adducts from lithium amides to aromatic aldehydes, iminium salts, animals, and N‐silylimines of aromatic aldehydes are coupled by the black suspension obtained from TiCL4 and Mg turnings in tetrahydrofuran (THF). The 1,2‐diarylethylenediamines with tertiary and primary amino groups thus obtained are formed with no or only moderate diastereoselectivity (products 4a–d (Scheme 2) and 5–e (Scheme 3), respectively); the amine component may contain a strained ring or additional heteroatoms as in azetidin, bis(2‐methoxyethyl)amine, piperazine, morpholine, and thiomorpholine (products 6a–e; Table 1). By an in‐situ procedure, ethylenediamines exclusively trans‐diaryl‐substituted piperazine and perhydro‐1,4‐diazepine derivatives (products 7a–f; Table 2). Enantiomerically pure monocyclic trans,cis‐5‐alkyl‐2,‐3‐diaryl‐piperazines and diazabicyclo[4.3.0]nonanes and ‐[4.4.0]decanes are obtained by employing suitable diamines prepared from the amino acids (S)‐alanine, (S)‐phenylalanine, (S)‐proline and from (S,S)‐ or (R,R)‐cyclohexane‐1,2‐diamine, respectively (products 11a–i, 7e; Table 4). The configuration of all products are derived from the high‐field NMR spectra, some of which are discussed in detail (Figs. 1 and 2, Tables 3 and 5); all new compounds are fully characterized by their physical data. Depending upon the structure of the components employed, the yields of purified products range from as low as 7% to essentially quantitative.

ELECTRON SPIN RESONANCE STUDY OF PHOSPHORANYL RADICALS I. INFLUENCE OF STERIC AND ELECTRONIC EFFECTS ON RADICAL FORMATION IN SOLUTION

Abstract An electron spin resonance study of phosphoranyl radicals, generated by u.v. irradiation of solutions containing a trialkylphosphite and a dialkylperoxide, enabled us to examine the influence of steric and electronic factors on radical formation. It was demonstrated that the influence of steric factors, such as α- or β-branching of the alkyl groups, on the magnitude of radical formation was present in both trialkyl- and methyldialkylphosphites, but not in dimethylalkylphosphites. Furthermore, the study of additional hetero atoms in the alkyl ligand of the dimethylalkylphosphites clearly revealed the influence of the gauche-effect. It was demonstrated that the presence of the gauche-effect, which causes a conformational preference in which a larger steric hindrance is produced, resulted in a decrease of radical formation.