Iodo Analogues Research Articles

Completion of Crystallographic Data for the Series of 4-Halogenated-1H-pyrazoles: Crystal Structure Determination of 4-Iodo-1H-pyrazole and Spectroscopic Comparison

Prior to 2021, 4-bromo-1H-pyrazole (published in 1999) was the only structurally characterized 4-halogenated-1H-pyrazole in the Cambridge Crystallographic Data Center (CCDC). The structures of 4-chloro-1H-pyrazole and 4-fluoro-1H-pyrazole were published in 2021 and 2023, respectively. Herein, we report the crystal structure for 4-iodo-1H-pyrazole, completing the crystallographic data for the series of 4-halogenated-1H-pyrazoles. The bromo and chloro analogs are isostructural, forming trimeric H-bonding motifs, whereas the fluoro and iodo analogs form non-isostructural catemers. We also compare the experimental and theoretical (by DFT calculations) IR and 1H NMR spectroscopic data of the four halogenated 4-X-pzH compounds and unsubstituted pyrazole (pzH). An explanation is offered for some counterintuitive structural, infrared, and 1H-NMR spectroscopic data.

Heptacoordinate Structures of Organotin Halides with Three Phosphine Donors: Halogen‐Substituent Effect on Geometry

Structural studies were performed on heptacoordinate compounds of triorganotin halides {(o‐Ph2P)C6H4}3SnX [X = F (1), Cl (3), Br (4), I (5)] with three phosphine donors. The fluorostannane (1) has an unusual heptacoordinate geometry, in which the three phosphine donors interact with the Sn center around the opposite coordination site of the Sn–F bond (a form). In contrast, the chloro (3) and bromo (4) analogues have highly distorted pentagonal‐bipyramidal geometries (b form), while the iodo analogue (5) has a tricapped tetrahedral geometry (c form). Although both b and c forms have two phosphine donors coordinating to the Sn center around the opposite site of the Cipso atoms and one phosphine donor coordinating to the Sn atom trans to the halogen atom, the geometry around the Sn center is much more distorted from tetrahedral geometry in b form than in c form. Density functional theory (DFT) calculations indicate that the presence of the halogen atom on the Sn center facilitates access from the opposite side of the halogen due to the strong electrostatic and intramolecular donor–acceptor transfer interactions. The difference in electronegativity of the halogen atoms also appear to contribute to structural modification by altering the halogen substituent, because a strongly electronegative halogen facilitates the formation of a structure that is highly distorted from the tetrahedral geometry (Bent's rule).

Application of an activity-based receptor bioassay to investigate the in vitro activity of selected indole- and indazole-3-carboxamide-based synthetic cannabinoids at CB1 and CB2 receptors.

Synthetic cannabinoids (SCs) are the most chemically diverse group of new psychoactive substances. This group has been associated with several intoxications, many with fatal outcomes. Although advancements have been achieved in pharmacology, metabolism, and detection of these compounds in recent years, these aspects are still unresolved for many SCs. The aim of this study was to investigate the in vitro potency of 14 indole- and indazole-based SCs by applying a stable CB1 or CB2 receptor activation assay and correlating the activity with their structure. The half-maximal effective concentration (EC50 ) of 5-chloropentyl, 5-bromopentyl, and 5-iodopentyl JWH-122 analogs varied from 74.1 to 283.7nM for CB1 and 7.05 to 23.4nM for CB2, where the addition of a chlorine atom enhanced the potency at CB1 compared with the bromo and iodo analogs. AM-2201 was the most active at CB1 within this naphthoylindole family, with an EC50 of 23.5nM but with the lowest efficacy (Emax 98.8%). Within the indole-3-carboxamide derivatives, 5F-MDMB-PICA was the most active compound, with a CB1/CB2 EC50 of 3.26/0.87nM and an Emax around three times higher than JWH-018. ADB-FUBINACA was the most potent tested SC overall, with a CB1/CB2 EC50 of 0.69/0.59nM, and an Emax around 3-fold higher than that for JWH-018 at CB1. The data obtained in this study confirm how small differences in the structure of SCs might lead to large differences in their activity, especially at CB1, which may be correlated with differences in their toxic effects in humans.

Dearomatization of the PCP Pincer Ligand in a ReV Oxo Complex.

A high-valent, rhenium(V) oxo complex (PCP)ReOCl2 (1; PCP=bis(2,6-di-tert-butylphosphinomethyl)phenyl) undergoes a deprotonation and "dearomatization" upon treatment with LiN(SiMe3 )2 to give (P*CP)ReOCl (2 a), in which Re is bound to a new dianionic P*CP ligand. Compound 2 a was studied spectroscopically, structurally, and computationally and was determined to have non-negligible Re=C multiple bond character, leading to its formulation as a new pseudo-carbenoid species. Reaction of 2 a or its iodo analogue (P*CP)ReOI (2 b) with CO2 provided access to (PCP)ReOX(CO2 ) (X=Cl or I, 3 a/b), the product of 1,3-cycloaddition and C-C bond formation.

Crystal structure, optical properties, and theory study of a 1-D bromoplumbate stabilized by in situ generated N-alkylated DABCO cation

We report the exploration of the stabilization effect of the in situ generated N-alkylated DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane) cation in the family of bromoplumbates and a 1-D bromoplumbate, (Et2DABCO)2n(Pb3Br10)n (1), has been prepared by solvothermal conditions. Optical diffuse reflectance determination shows the band gap of 1 is 3.69 eV, which manifests that 1 is a wide band gap semiconductor. Compared with the band gap of bulk PbBr2 (3.84 eV), 1 exhibits 0.15 eV red shift of absorption edge. While for the reported iodo analogs of this compound, (MPDA)2n(Pb3I10)n and (Et2DABCO)2n(Pb3I10)n, they exhibit 0.53 and 0.47 eV blue shift of the energy gaps compared with the measured value of 2.30 eV for bulk PbI2, respectively. The photoluminescent study of 1 shows that it exhibits a broad emission band centered at 697 nm upon photoexcitation by 345 nm (amount to 3.59 eV). The calculated density of states manifests the theoretical value of the band gap of 1 is 3.422 eV and the origination of photoluminescence can be ascribed to the transition of bonding electrons of Br– anion to the empty orbits of Pb(II) ion.

Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I.

2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) has recently emerged as a new psychoactive substance (NPS). It is most commonly consumed orally, although there are indications that it might also be ingested by inhalation or 'smoking'. Information about the stability of bk-2C-B when exposed to heat is unavailable and the potential for pyrolytic degradation and formation of unknown substances available for inhalation prompted an investigation using a simulated 'meth pipe' scenario. Twelve products following pyrolysis of bk-2C-B were detected and verified by organic synthesis of the corresponding standards. In addition, 2-amino-1-(4-iodo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-I) was characterized for the first time and subjected to pyrolysis as well. Similar products were formed, which indicated that the replacement of the bromo with the iodo substituent did not affect the pyrolysis pattern under the conditions used. Two additional products were detected in the bk-2C-I pyrolates, namely 1-(2,5-dimethoxyphenyl)-ethanone and 1-iodo-4-ethenyl-5-methoxyphenol. The potential ingestion of pyrolysis products with unknown toxicity adds an element of concern. Copyright © 2017 John Wiley & Sons, Ltd.

On the cause of low thermal stability of ethyl halodiazoacetates.

Rates for the thermal decomposition of ethyl halodiazoacetates (halo = Cl, Br, I) have been obtained, and reported herein are their half-lives. The experimental results are supported by DFT calculations, and we provide a possible explanation for the reduced thermal stability of ethyl halodiazoacetates compared to ethyl diazoacetate and for the relative decomposition rates between the chloro, bromo and iodo analogs. We have also briefly studied the thermal, non-catalytic cyclopropanation of styrenes and compared the results to the analogous Rh(II)-catalyzed reactions.

Synthesis and evaluation of a radioiodinated 4,6-diaryl-3-cyano-2-pyridinone derivative as a survivin targeting SPECT probe for tumor imaging.

Survivin is overexpressed in most of the cancerous tissues but not in terminally differentiated normal tissues, making it an attractive target for diagnosis and therapy of various types of cancers. In this study, we aimed to develop 4,6-diaryl-3-cyano-2-pyridinone (DCP) derivatives, as novel cancer imaging probes that target survivin. Chloro and iodo analogs of DCP (CDCP and IDCP, respectively) were successfully synthesized by using a previously unreported carbon monoxide-free procedure. IDCP exhibited a slightly higher binding affinity for recombinant human survivin (Kd=34 nM) than that of CDCP (Kd=44 nM). Fluorescence staining indicated that both CDCP and IDCP showed high signals in MDA-MB-231 cells with high levels of survivin expression. Significantly low fluorescent signals were observed in MCF-10A cells, which showed low levels of survivin expression. [(125)I]IDCP was synthesized for the application of IDCP to single photon emission computed tomography (SPECT) imaging. Quantitative in vitro binding of [(125)I]IDCP in cell cultures showed results consistent to those observed after fluorescent staining. In vivo biodistribution studies in tumor-bearing mice demonstrated that the tumor uptake of [(125)I]IDCP increased gradually with time and was 0.65% injected dose per gram (% ID/g) at 180 min. The maximum tumor/blood and tumor/muscle ratio at 60 min were 0.87 and 2.27, respectively, indicating inadequate [(125)I]IDCP accumulation in tumors necessary for in vivo imaging. Although further structural modifications are necessary to improve pharmacokinetic properties of IDCP, this study demonstrates the feasibility of using the DCP backbone as a scaffold for the development of survivin-targeting tumor imaging probes.

Oxidative addition at a carbene center: synthesis of an iminoboryl-CAAC adduct.

The reaction of a cyclic (alkyl)(amino)carbene (CAAC) with dichloro- and dibromobis(trimethylsilyl)aminoborane results in the formation of haloiminoborane-CAAC adducts. When the iodo analogue is used, an oxidative addition at the carbene center affords a cationic iminoboryl-CAAC adduct, featuring a boron-nitrogen triple bond. Similar salts are also obtained by halide abstraction from the chloro- and bromoiminoborane-CAAC adducts. The reactivity of all of these compounds towards CO2 is discussed.

Peculiar Features in the Crystal Structure of the Adduct Formed betweencis-PtI2(NH3)2and Hen Egg White Lysozyme

The reactivity of cis-diamminediiodidoplatinum(II), cis-PtI2(NH3)2, the iodo analogue of cisplatin, with hen egg white lysozyme (HEWL) was investigated by electrospray ionization mass spectrometry and X-ray crystallography. Interestingly, the study compound forms a stable 1:1 protein adduct for which the crystal structure was solved at 1.99 Å resolution. In this adduct, the Pt(II) center, upon release of one ammonia ligand, selectively coordinates to the imidazole of His15. Both iodide ligands remain bound to platinum, with this being a highly peculiar and unexpected feature. Notably, two equivalent modes of Pt(II) binding are possible that differ only in the location of I atoms with respect to ND1 of His15. The structure of the adduct was compared with that of HEWL-cisplatin, previously described; differences are stressed and their important mechanistic implications discussed.

Improved synthesis of 17β-hydroxy-16α-iodo-wortmannin, 17β-hydroxy-16α-iodoPX866, and the [131I] analogue as useful PET tracers for PI3-kinase

An improved method for the synthesis of 17β-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17β-hydroxy-16α-iodoPX866 and [131I] radiolabeled 17β-hydroxy-16α-[131I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K.

Tellurium derivatives of 3-acetyl-2,5-dimethylthiophene: Synthetic and structural aspects

Oxidative addition of α-bromo-3-acetyl-2,5-dimethylthiophene to elemental tellurium and aryltellurium(II) bromide provides direct routes to (2,5-dimethyl-3-thiophenoylmethyl)tellurium(IV) dibromides, (Me2TpnCOCH2)2TeBr2 (1a; Me2Tpn = 2,5-Me2-3-C4HS) and Ar(Me2TpnCOCH2)TeBr2 (Ar = 1-C10H7, Npl, 2a; 2,4,6-Me3C6H2, Mes, 3a). The chloro analogs of 2a and 3a, Ar(Me2TpnCOCH2)TeCl2 (Ar = Npl, 2b; Mes, 3b) and derivative when Ar = Anisyl (anisyl = 4-MeOC6H4, 4b) were prepared by the condensation reaction of methyl ketone, Me2TpnCOCH3 with NplTeCl3, MesTeCl3 and anisylTeCl3 respectively while the chloro analog of 1a, bis(2,5-dimethyl-3-thiophenoylmethyl)tellurium(IV) dichloride, (Me2TpnCOCH2)2TeCl2 (1b) was obtained by the condensation reaction of methyl ketone, Me2TpnCOCH3 with TeCl4. Metathesis of these products (1a–b, 2a–b, 3a–b and 4b) with an alkali iodide affords the iodo analogs 1c, 2c, 3c and 4c. These diorganotellurium dihalides are reduced with aqueous bisulfite to diorganotellurides 1–4, which can be oxidized readily with dihalogens to the desired diorganotellurium(IV) dihalides. The crystal structures of the Te(IV) compounds 1b, 2a, 3c and 4b have been studied and all the Te(IV) compounds, the carbonyl functionalized organic moiety, show intramolecular 1,4–Te⋯O secondary bonding interaction (SBI). In the crystal lattice of 2a, the intermolecular Te⋯Br secondary bonding interactions are evident and result in a dimer. They get further associated via C–H⋯Br secondary interactions to form a 3D supramolecular motifs. In 1b, 3c and 4b supramolecular motifs are formed through C–H⋯O and C–H⋯Cl interactions.

Substitution reactions on a hypercoordinated main-group element encapsulated in a pentacapped trigonal prismatic copper cage

Compound 1, [Cu11(μ9-Br)(μ3-Br)3{S2P(O(i)Pr)2}6](+), containing the first μ9-bromide at the center of a pentacapped trigonal-prismatic copper skeleton, was isolated from the reaction of [Cu(CH3CN)4](PF6), NH4[S2P(O(i)Pr)2], and Bu4NBr in 11:6:4 ratios in methanol. Treatment of 1 with Bu4NI resulted in a complete replacement of four bromides to yield a corresponding iodo analogue {Cu11(I)(I)3[S2P(O(i)Pr)2]6}(+), 2. The central bromide and iodide in 1 and 2 can be replaced by a sulfide generated in situ from Na2S2O3 to produce [Cu11(μ9-S)(μ3-X)3{S2P(O(i)Pr)2}6] (X = Br, 3; I, 4). All four compounds displayed interesting photoluminescent properties.

ChemInform Abstract: A Convenient Metal‐Free Method for the Synthesis of Benzothiazolethiones from o‐Haloanilines and Carbon Disulfide.

Abstracto‐Bromoanilines including N‐substituted derivatives and the iodo analogue (Ia) are transformed to the desired products in the presence of CS2 and DBU.

A Photochemical Route to 2-Substituted Benzo[b]furans

2-Substituted benzo[b]furans were synthesized by a one-step metal-free photochemical reaction between 2-chlorophenol derivatives and terminal alkynes by tandem formation of an aryl-C and a C-O bond via an aryl cation intermediate. The mild conditions and the application to chlorophenols rather of the more expensive bromo or iodo analogues makes this procedure environmentally convenient.

Synthesis and Crystallography of 8-Halonaphthalene-1-Carbonitriles and Naphthalene-1,8-Dicarbonitrile

A convenient and high-yielding three-step synthesis of 8-halonaphthalene-1-carbonitriles has been achieved by ring opening of 1H-naphtho[1,8-de][1,2,3]triazine with the corresponding halides as the key step. Naphthalene-1,8-dicarbonitrile also has been synthesised from 8-bromonaphthalene-1-carbonitrile via palladium-catalysed cyanation of the aryl bromide. The crystal structures of 8-chloronaphthalene-1-carbonitrile, the A polymorph of the bromo analogue, and naphthalene-1,8-dicarbonitrile are isomorphous with orthorhombic symmetry. The B polymorph of the bromo compound and the iodo analogue are also isomorphous, but with monoclinic symmetry. In all of the halo carbonitriles, the molecules are disordered with respect to the location of the halogen atoms and the nitrile groups. There are no intermolecular X···NC interactions in any of the solids.

Furan derivatives of tellurium: Synthesis and structural comparison with the thiophene analogues

α-Bromo-2-acetylfuran adds oxidatively to elemental tellurium and aryltellurium(II) bromide at ambient temperature to afford (2-furoylmethyl)tellurium(IV) dibromides, (FuCOCH 2) 2TeBr 2 ( 1b) and Ar(FuCOCH 2)TeBr 2 (Fu = 2-C 4H 3O; Ar = 1-C 10H 7, 2b; 2,4,6-Me 3C 6H 2, 3b). The iodo analogues 1c– 3c can be obtained by metathesis of the bromides with an alkali iodide. Condensation reactions of the parent methyl ketone with Te(IV) chlorides results in the corresponding chloro analogues, (FuCOCH 2) 2TeCl 2 ( 1a) and Ar(FuCOCH 2)TeCl 2 ( 2a, 3a and Ar = 4-MeOC 6H 4 ( 4a)). These diorganotellurium dihalides are reduced with aqueous bisulfite to diorganotellurides 1– 3, which can be oxidized readily with dihalogens to the desired diorganotellurium(IV) dihalides. The tellurated furan derivative, bis(2-furyl)tellurium(II), Fu 2Te ( 5), obtained by detelluration of bis(2-furyl)ditelluride with electrolytic copper, gives crystalline bis(2-furyl)tellurium(IV) dichloride ( 5a) upon chlorination. Crystal structures of Te(IV) compounds 1a, 1b, 2a– 4a, and the telluride 3 together with its thiophene analogue (2,4,6-Me 3C 6H 2)((2-C 4H 3S)COCH 2)Te, 6 have been studied. Among the Te(IV) compounds, the functionalized organic moiety, FuCOCH 2-, behaves as a (C, O) chelating ligand, resulting in a intramolecular 1,4-Te⋯O secondary bonding interaction. Such an interaction is absent in Te(II) compounds 3 and 6, though they differ in the conformation adopted by the organic ligand. The chalcogen atoms in the heteroaroyl moiety are trans in 3 but cis in 6 which also possesses intermolecular Te⋯O interaction in its lattice.

Methyl 6-azido-6-deoxy-α-D-galactoside

The structure of the title compound, C7H13N3O5, was solved using data from a multiple fragment crystal. The galactoside ring adopts a 4 C 1 chair conformation. In the crystal, the molecules are linked by strong O—H⋯O hydrogen bonds, which build linkages around the screw axis of the cell in a similar way to the iodo analogue. These C-5 and C-6 packing motifs expand to R 2 2(10), C 2 2(7) and C 2 2 2(8) motifs, as found in closely related compounds.

Palladium selenolates via oxidative addition of organylselenenyl halides to palladium(0) precursor and via cleavage reaction of diselenides: Synthesis, structure and spectroscopic investigation

Oxidative addition of bis[2-(4,4-dimethyl-2-oxazolinyl)phenyl] diselenide to Pd(PPh 3) 4 provided two different mononuclear palladium selenolato complexes, Pd(Se∩N)(PPh 3)Cl ( 4) [Se∩N = chelating 2-(4,4-dimethyl-2-oxazolinyl)phenylselenolate] and Pd(Se∩N)(Se∩N*)(PPh 3) ( 5) [Se∩N = chelating, Se∩N* = non-chelating 2-(4,4-dimethyl-2-oxazolinyl)phenylselenolato ligand] in dicholoromethane and toluene respectively. Complex 4 has also been synthesized by the oxidative addition of 2-(4,4-dimethyl-2-oxazolinyl)phenylselenenyl chloride to Pd(PPh 3) 4. The bromo and iodo analogs of 4 ( 9 and 10) were similarly synthesized by the oxidative addition of 2-(4,4-dimethyl-2-oxazolinyl)phenylselenenyl bromide and iodide, respectively to Pd(PPh 3) 4. The oxidative addition of 2-( N, N-dimethylaminomethyl)phenylselenenyl bromide and iodide to Pd(PPh 3) 4 afforded mononuclear palladium selenolate complexes, Pd(Se∩N)(PPh 3)X ( 13 and 14) [Se∩N = chelating 2-( N, N-dimethylaminomethyl)phenylselenolate, X = Br: 13, X = I: 14]. The reactions of bis[2-(4,4-dimethyl-2-oxazolinyl)phenyl] diselenide and bis[2-( N, N-dimethylaminomethyl)phenyl] diselenide with Pd(COD)Cl 2 provided dinuclear selenolato-bridged complexes [PdCl(Se∩N)] 2 ( 15) [Se∩N = chelating 2-(4,4-dimethyl-2-oxazolinyl)phenylselenolate] and [PdCl(Se∩N)] 2 ( 19) [Se∩N = chelating 2-( N, N-dimethylaminomethyl)phenylselenolate] respectively. The complexes were characterized by elemental analysis and NMR ( 1H and 77Se) spectroscopy. Complexes 4 and 5 were also characterized by mass spectrometry. Molecular structures of 4, 5, 9, 14 and 15 have been established by single crystal X-ray diffraction analysis. Complexes 4 and 9 are isomorphous and crystallize in the space group P2 1/ c of the monoclinic system where the selenolato and halo ligands are trans to each other. Complex 5 crystallizes in the space group P2 1/ n of the monoclinic system where one chelating and one non-chelating selenolato ligands are trans to each other. Mononuclear complex 14 and binuclear centrosymmetric complex 15 crystallize in the P 1 ¯ space group of the triclinic system.

Excretion and storage of 131 I labelled iodo analogue of chlorotrianisene.

Excretion and storage of 131 I labelled iodo analogue of chlorotrianisene.