Halogen Exchange Reaction Research Articles

Near-Interfacial Halogen Atom Exchange in Collisions of Cl2 with 2.7 M NaBr–Glycerol

Gas-liquid scattering experiments are used to investigate reactions of Cl(2) with a 2.7 M NaBr-glycerol solution at 291 K. Only the single and double halogen exchange products, BrCl and Br(2), are observed to desorb from solution. When Cl(2) molecules strike the surface at thermal collision energies, 76% desorb as Cl(2) before reacting, 1% react to form BrCl, and 23% react to form Br(2). Residence time measurements, modeled by mass-transfer equations for absorption, diffusion, reaction, and evaporation, were used to determine the time and depth scales for Cl(2) escape and BrCl and Br(2) production. This modeling indicates that Cl(2) molecules desorb from the interfacial region in less than 1 μs or are attacked within this time by Br(-) ions and irreversibly captured as Cl(2)Br(-). The products BrCl and Br(2) are created primarily within the top few monolayers of the solution and then evaporate on average 12 and 28 μs after Cl(2) initially reacts with Br(-). Notably, Br(2) is not generated from BrCl via Cl(2)Br(-) → BrCl + Cl(-) and BrCl + Br(-) → Br(2)Cl(-) but from the parallel reaction Cl(2)Br(-) + Br(-) → Br(2)Cl(-)+ Cl(-) that bypasses the BrCl intermediate. Br(2) is then likely released through two pathways, Br(2)Cl(-) → Br(2) + Cl(-) and Br(2)Cl(-) + Br(-) → Br(3)(-) + Cl(-), followed by Br(3)(-) ↔ Br(2) + Br(-). The experiments demonstrate that single and double halogen exchange reactions can occur rapidly and close to the surface even when the products are created by multiple sequential reactions.

A Halomethane Thermochemical Network from iPEPICO Experiments and Quantum Chemical Calculations

Internal energy selected halomethane cations CH(3)Cl(+), CH(2)Cl(2)(+), CHCl(3)(+), CH(3)F(+), CH(2)F(2)(+), CHClF(2)(+), and CBrClF(2)(+) were prepared by vacuum ultraviolet photoionization, and their lowest energy dissociation channel studied using imaging photoelectron photoion coincidence spectroscopy (iPEPICO). This channel involves hydrogen atom loss for CH(3)F(+), CH(2)F(2)(+), and CH(3)Cl(+), chlorine atom loss for CH(2)Cl(2)(+), CHCl(3)(+), and CHClF(2)(+), and bromine atom loss for CBrClF(2)(+). Accurate 0 K appearance energies, in conjunction with ab initio isodesmic and halogen exchange reaction energies, establish a thermochemical network, which is optimized to update and confirm the enthalpies of formation of the sample molecules and their dissociative photoionization products. The ground electronic states of CHCl(3)(+), CHClF(2)(+), and CBrClF(2)(+) do not confirm to the deep well assumption, and the experimental breakdown curve deviates from the deep-well model at low energies. Breakdown curve analysis of such shallow well systems supplies a satisfactorily succinct route to the adiabatic ionization energy of the parent molecule, particularly if the threshold photoelectron spectrum is not resolved and a purely computational route is unfeasible. The ionization energies have been found to be 11.47 ± 0.01 eV, 12.30 ± 0.02 eV, and 11.23 ± 0.03 eV for CHCl(3), CHClF(2), and CBrClF(2), respectively. The updated 0 K enthalpies of formation, Δ(f)H(o)(0K)(g) for the ions CH(2)F(+), CHF(2)(+), CHCl(2)(+), CCl(3)(+), CCl(2)F(+), and CClF(2)(+) have been derived to be 844.4 ± 2.1, 601.6 ± 2.7, 890.3 ± 2.2, 849.8 ± 3.2, 701.2 ± 3.3, and 552.2 ± 3.4 kJ mol(-1), respectively. The Δ(f)H(o)(0K)(g) values for the neutrals CCl(4), CBrClF(2), CClF(3), CCl(2)F(2), and CCl(3)F and have been determined to be -94.0 ± 3.2, -446.6 ± 2.7, -702.1 ± 3.5, -487.8 ± 3.4, and -285.2 ± 3.2 kJ mol(-1), respectively.

Analytical and Biological Characterization of Halogenated Gemfibrozil Produced through Chlorination of Wastewater

The cholesterol-lowering pharmaceutical gemfibrozil is a relevant environmental contaminant because of its frequency of detection in U.S. wastewaters at concentrations which have been shown to disrupt endocrine function in aquatic species. The treatment of gemfibrozil solutions with sodium hypochlorite yielded a 4'-chlorinated gemfibrozil analog (chlorogemfibrozil). In the presence of bromide ion, as is often encountered in municipal wastewater, hypobromous acid generated through a halogen exchange reaction produced an additional 4'-brominated gemfibrozil product (bromogemfibrozil). Standards of chloro- and bromogemfibrozil were synthesized, isolated and characterized using mass spectrometry and NMR spectroscopy. Mass spectrometry was used to follow the in situ halogenation reaction of gemfibrozil in deionized water and wastewater matrices, and to measure levels of gemfibrozil (254 ± 20 ng/L), chlorogemfibrozil (166 ± 121 ng/L), and bromogemfibrozil (50 ± 11 ng/L) in advanced primary wastewater treatment effluent treated by chlorination. Chlorogemfibrozil demonstrated a significant (p < 0.05) reduction in the levels of 11-ketotestosterone at 55.1 μg/L and bromogemfibrozil demonstrated a significant (p < 0.05) reduction in the levels of testosterone at 58.8 μg/L in vivo in Japanese medaka in a 21 day exposure. These results indicated that aqueous exposure to halogenated degradates of gemfibrozil enhanced the antiandrogenicity of the parent compound in a model fish species, demonstrating that chlorination may increase the toxicity of pharmaceutically active compounds in surface water.

Copper(I)-promoted halogen exchange in the iron(II) dichloroclathrochelate

Abstract The halogen exchange reaction of the macrobicyclic iron(II) complex FeBd2(Cl2Gm)(BF)2 (where Bd2– and Cl2Gm2– are α-benzyldioxime and dichloroglyoxime dianions, respectively) with two-fold excess of CuI and stoichiometric amounts of NaI in NMP gave the mixture of initial compound with diiodo- and iodochloroclathrochelates as well as the small amounts of the cage by-products of side hydrodehalogenation and homo-coupling reactions of this precursor. The chromatographically isolated complex FeBd2(IGmCl)(BF)2 has been characterized using elemental analysis, MALDI-TOF mass spectrometry, IR, UV–vis, 1H and 13C{1H} NMR spectroscopies, and X-ray diffraction crystallography. This clathrochelate possess a geometry intermediate between that of a trigonal prism and a trigonal antiprism (the distortion angle φ = 23.6°). The Fe–N distances vary in a narrow range (1.91–1.92 A), the height h of the FeN6-coordination polyhedron and the averaged bite angle α are equal to 2.34 A and 39.2°, respectively. The reaction studied occurs only in the case of the vic-dihalogenosubstituted macrobicycles with CuI as both the catalyst and the reagent, and with iodide anions coordinated to the copper(I) ions. The proposed mechanism of this reaction is similar to that for copper-catalyzed Finkelstein-type reactions of aryl halides and the intermediate anion-radical species are effectively generated with CuI–N-methylpyrrolidone complex.

ChemInform Abstract: One‐Pot Preparation of Hydroxylated Potassium Organotrifluoroborates and Subsequent Jones Oxidation to Potassium Organocarbonyltrifluoroborates.

AbstractDibromobenzenes (I) or (VII) and a range of aromatic and aliphatic aldehydes are sequentially transformed into alcohol‐containing organotrifluoroborates via lithium—halogen exchange reactions.

5-Chloroindole계 화합물의 Large Scale 합성

A large scale and commercially feasible synthesis of 5-chloroindole and its 3-substituted analogues has been described via a halogen - halogen exchange reaction from 5-bromoindole and its derivatives using cuprous chloride and dipolar aprotic solvent N-methyl-2-pyrrolidone in one pot with good yields.

Noncryogenic Preparation of Functionalized Arylboronic Esters through a Magnesium−Iodine Exchange with in Situ Quench

Various functionalized aryl boronic esters derived from hexylene glycol and pinacol were prepared in excellent yields according to a simple, safe procedure. The metal−halogen exchange reaction between iPrMgCl·LiCl and aryl iodides is performed at 0 °C in the presence of a cyclic borate ester (MPBOiPr or PinBOiPr); the organomagnesium intermediate is immediately trapped in situ so that no accumulation of hazardous reactive species can occur. The reaction is very selective, and particularly clean crude products are obtained. The scope of the procedure and the tuning of reaction parameters are investigated.

ChemInform Abstract: “Cage‐Like” Phosphines: Design and Catalytic Properties

AbstractReview: 76 refs.

4′-(o-Toluyl)-2,2′ : 6′,2′′-terpyridine: synthesis, bromination, complexation, and X-ray crystallographic characterization

The ligands 4′-(o-toluyl)-2,2′ : 6′,2″-terpyridine and 4′-[2-(bromomethyl)phenyl]-2,2′ : 6′,2″-terpyridine were synthesized. X-ray crystallographic studies have been performed on complexes that were prepared using these ligands. In one case, a halogen exchange reaction occurs, resulting in a dinuclear copper complex in which the bromine in the terpyridine derivative is replaced by chlorine and is ultimately found as a disordered bridging bromide.

Synthesis and applications of cross-linked poly(diallyldimethyl ammonium chloride) and its derivative copolymers as efficient phase transfer catalyst for nucleophilic substitution reactions

Cross-linked poly(diallyldimethylammonium chloride) and its derivative copolymers were synthesized and used as phase transfer catalyst in the nucleophilic substitution reaction especially halogen exchange reactions. In addition, the effect of hydrophilic-hydrophobic character of the polymers in the nucleophilic reactions was investigated.

Towards Halomethylated Benzene-Bearing Monomeric and Polymeric Substrates

This paper presents the trends in the halomethylation reaction of aromatic hydrocarbons and polymeric analogues. Much interest is devoted to the chloromethylation vis-à-vis other halomethylations, even though the incorporated chloromethyl group is the least chemically reactive among the common halomethyl groups (CH2Cl, CH2Br, CH2I). While bromomethylation stands second behind chloromethylation in terms of chemists' interest, a few cases of iodomethylation are cited, and only one case of fluoromethylation was reported. Various halomethylating systems have been devised, starting from the early one, paraformaldehyde/hydrogen halide, then those involving the in situ formation of halomethyl methyl ether (HalMME), and ending with those giving rise to other intermediate halomethylating species. Halomethylated aromatic polymers, including even the fluoromethylated ones, can be achieved by other means, such as polymerization of halomethyl-containing monomers, halogenation of pendent methyl groups and halogen exchange reaction (halex reaction) within halomethyl groups. Reaction conditions, i.e., solvents, catalysts and promoters, are surveyed. Exploitation of the concomitant Friedel–Crafts alkylation in the course of halomethylation is illustrated by some examples. In addition, the quaternization of halomethylated aromatic polymers (particularly the chloromethylation) is inevitably linked to halomethylation; thus, it is selectively evoked to valorize further the halomethylation reaction.

Syntheses and properties of triborane(5)s possessing bulky diamino substituents on terminal boron atoms

The present communication reports the chemistry of three linear triborane(5) compounds possessing bulky diamino substituents on the terminal boron atoms. Fluorotriborane 2 was synthesized by a reaction of boryllithium and BF(3)·OEt(2). Halogen exchange reaction of 2 took place by a treatment with ClSiMe(3) to give the corresponding chlorotriborane(5) 3. Addition of silver tetraarylborate to 3 in ether afforded a hydroxylated triborane(5) compound 5 probably via an unstable cationic boron intermediate 4.

Electrophilic cyclization of 3-alkynyl-4-chalcogen-2-H-chromenes: synthesis of 3-halo-chalcogenophene[3,2-c]chromene derivatives

An efficient synthesis of 3-halo-chalcogenophene[3,2-c]chromene has been accomplished via electrophilic cyclization reaction of 3-alkynyl-4-chalcogen-2H-chromene using I2, PhSeBr, and BuTeBr3 as electrophilic sources. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-halochalcogen-chromenes were formed in good yields. In addition, the obtained 3-iodo-chalcogenophene-chromenes were readily transformed to more complex products using a metal–halogen exchange reaction with n-BuLi and trapping the lithium-intermediate formed with aldehyde, furnishing the desired secondary alcohol in good yield. Conversely, using the palladium catalyzed cross-coupling reactions with terminal alkynes and boronic acid, we were able to obtain the Sonogashira and Suzuki type products in good yields.

Rhodium-Catalyzed Activation of C(sp3)−X (X = Cl, Br) Bond: An Intermolecular Halogen Exchange Case

A RhCl(PPh(3))(3)-catalyzed halogen-exchange reaction between allyl and alkyl halides with β-H atoms was observed. The possible mechanism of the reaction involves oxidative addition and reductive elimination of the C(sp(3))-X bonds, which is not common in organometallic chemistry.

“Cage‐Like” Phosphines: Design and Catalytic Properties

AbstractThe need to design organocatalysts or water‐soluble catalysts for a number of reactions of industrial interest helps explain the renewed interest in ligands which allow such reactions to take place. Among them, “cage‐like” phosphines, known for some time, offer new perspectives as also do their corresponding metal transition complexes. The role of some of these ligands, such as Verkade‐type bases, 1,3,5‐triaza‐7‐phosphatricyclo[3.3.1.1]decane (PTA), 2,4,10‐trimethyl‐1,2,4,7,10‐hexaaza‐3‐phosphatricyclo[3.3.1.13,7]decane (THPA), and tris(1,2‐dimethylhydrazino)diphosphine (THDP), as central tools with broad functional group tolerance for CC, CO, CN bond formation, halogen exchange reactions, isomerization of allylic alcohols, cycloisomerization as well as Kharasch reactions are highlighted with selected examples.

ChemInform Abstract: The Mechanism of the Hydroxyl → Halogen Exchange Reaction in the Presence of Triphenylphosphine, N-Bromosuccinimide, and N,N- Dimethylformamide: Application of a New Vilsmeier Type Reagent in Carbohydrate Chemistry.

Abstract Triphenylphosphine reacts with N -bromosuccinimide to give a phosphonium salt ( 13 ), which reacts with N,N -dimethylformamide to afford N,N -dimethylsuccinimidomethaniminium bromide ( 16 ). The latter product reacts with an alcohol to give an O -forminimium compound 17 , and, in the presence of an alcohol, 13 is transformed into an alkoxyphsphonium intermediate ( 14 ). Both 14 and 17 can be converted by heating into an alkyl bromide. Hydrolysis of 17 gives the corresponding O -formyl derivative. Reaction of 1.2:5.6-di- O -isopropylidene-α- d -glucofuranose with 13 or 16 gave 6-bromo-6-deoxy-1,2:3,5-di- O -isopropylidene-α- d -glucofuranose and a possible mechanism for these reactions is suggested. An efficient method for the preparation of 3-deoxy-3-halogeno-1,2:5,6-di- O -isopropylidene-α- d -allofuranose derivatives and a new procedure for selective O -formylation are described.

PET Imaging of Norepinephrine Transporter–Expressing Tumors Using 76Br-meta-Bromobenzylguanidine

Meta-iodobenzylguanidine (MIBG) labeled with (123)I or (131)I has been widely used for the diagnosis and radiotherapy of norepinephrine transporter (NET)-expressing tumors. However, (123)I/(131)I-MIBG has limitations for detecting small lesions because of its lower spatial resolution than PET tracers. In this study, meta-bromobenzylguanidine (MBBG) labeled with (76)Br (half-life, 16.1 h), an attractive positron emitter, was prepared and evaluated as a potential PET tracer for imaging NET-expressing tumors. (76)Br-MBBG was prepared by a halogen-exchange reaction between the (76)Br and iodine of nonradioactive MIBG. The stability of MBBG was evaluated in vitro and in vivo by high-performance liquid chromatography analysis. Cellular uptake studies with or without NET inhibitors were performed in NET-positive PC-12 cell lines. Biodistribution studies were performed in PC-12 tumor-bearing nude mice by administration of a mixed solution of MBBG, MIBG, and (18)F-FDG. The tumor was imaged using (76)Br-MBBG and (18)F-FDG with a small-animal PET scanner. MBBG was stable in vitro, but some time-dependent dehalogenation was observed after administration in mice. MBBG showed high uptake in PC-12 tumor cells that was significantly decreased by the addition of NET inhibitors. In biodistribution studies, MBBG showed high tumor accumulation (32.0 +/- 18.6 percentage injected dose per gram at 3 h after administration), and the tumor-to-blood ratio reached as high as 54.4 +/- 31.9 at 3 h after administration. The tumor uptake of MBBG correlated well with that of MIBG (r = 0.997) but not with that of (18)F-FDG. (76)Br-MBBG PET showed a clear image of the transplanted tumor, with high sensitivity, which was different from the lesion shown by (18)F-FDG PET. (76)Br-MBBG showed high tumor accumulation, which correlated well with that of MIBG, and provided a clear PET image. These results indicated that (76)Br-MBBG would be a potential PET tracer for imaging NET-expressing neuroendocrine tumors and could provide useful information for determining the indications for (131)I-MIBG therapy.

Syntheses, solid-state structures, solution behavior of hypervalent organobismuth(III) compounds [2-(Et 2NCH 2)C 6H 4] nBiX 3−n and DFT characterization of [2-(Me 2NCH 2)C 6H 4] nBiX 3−n [X = Cl, Br, I; n = 1–3

The reaction of RLi [R = 2-(Et 2NCH 2)C 6H 4] with BiCl 3 in 3:1 or 2:1 molar ratio afforded R 3Bi ( 1) and R 2BiCl ( 2), respectively. Redistribution reactions between 1 and BiCl 3 (1:2 molar ratio) resulted in RBiCl 2 ( 5). R 2BiBr ( 3) formed from RMgBr and BiCl 3 (2:1 molar ratio). R 2BiI ( 4) and RBiX 2 [X = Br ( 6), I ( 7)] were obtained from 2 and 5 by halogen-exchange reactions using KX in water/CH 2Cl 2 mixture. Compounds 1– 7 were characterized by FT-Raman/IR, 1H and 13C NMR spectroscopies as well as mass spectrometry. The structures of 1– 4 were determined by single-crystal X-ray diffraction. They all have pyramidal C 3Bi or C 2BiX cores. For R 3Bi ( 1) intramolecular N → Bi interactions of medium strength [Bi(1)–N(1) 3.214(7) Å] result in an overall distorted octahedral ( C, N) 3Bi core. In the monohalides 2– 4 one nitrogen is strongly coordinated to bismuth trans to the halogen [range 2.571(8)–2.645(6) Å], while the second one is involved in a considerably weaker intramolecular N → Bi interaction trans to a carbon atom [range 2.992(12)–3.170(8) Å]. The overall ( C, N) 2BiX (X = Cl, Br, I) core is distorted square-pyramidal. The NMR studies provided evidence for the presence of internal nitrogen-bismuth coordination in solution for RBiX 2 species. DFT calculations were performed on the related compounds R′BiX 2 [X = Cl ( 8), Br ( 9), and I ( 10)], R′ 2BiX [X = Cl ( 11), Br ( 12), and I ( 13)], and R′ 3Bi ( 14) [R′ = 2-(Me 2NCH 2)C 6H 4] in order to elucidate the bond nature and vibrational spectroscopic features of this class of organobismuth(III) compounds.

New chiral organoantimony(iii) compounds containing intramolecular N → Sb interactions – solution behaviour and solid state structures

Hypervalent organoantimony(III) compounds of the type [2-(Me2NCH2)C6H4]PhSbCl (1), [2-(Me2NCH2)C6H4]MesSbBr (7) and [2-(Me2NCH2)C6H4]nAr(3-n)Sb [n = 1, Ar = Ph (4), Mes (9); n = 2, Ar = Ph (5), Mes (10)] were prepared via salt elimination reactions between [2-(Me2NCH2)C6H4]Li and MesMgBr and PhnSbCl(3-n), [2-(Me2NCH2)C6H4]SbBr2 or [2-(Me2NCH2)C6H4]nSbCl(3-n) (n = 1, 2), in appropriate molar ratios. Halogen exchange reactions with aqueous KBr or KI gave [2-(Me2NCH2)C6H4]ArSbX [Ar = Ph, X = Br (2), I (3); Ar = Mes, X = I (8)]. Metathesis reaction between 1 and MesMgBr affords [2-(Me2NCH2)C6H4]PhMesSb (6). Compounds 1-10 were investigated by means of NMR (1H, 13C) in solution and by mass spectrometry. The investigation of the molecular structures of 2-8 by single-crystal X-ray diffraction revealed that the nitrogen atoms of the pendant CH2NMe2 arms are strongly coordinated to the antimony atoms. All compounds exhibit chirality and crystallize as racemic mixtures.

Isolation of 1,4-Li2-C6H4 and its reaction with [(Ph3P)AuCl

The difficulty in generating 1,4-Li2-C6H4 utilising the lithium halogen exchange reaction on 1,4-Br2-C6H4, 1,4-I2-C6H4 and 1-Br-4-I-C6H4 is revisited and only on treatment of 1,4-I2-C6H4 with 2 molar equivalents of n-BuLi can 1,4-Li2-C6H4 1 be isolated in excellent yield. Treatment of 1 with two equivalents of [ClAu(PPh3)] gives [1,4-(Ph3PAu)2-C6H4] 2a in excellent yield. Subsequent treatment of 2a with 2.5 molar equivalents of PPh2Me, PPhMe2 or PMe3 affords the PPh3 substituted compounds [1,4-(LAu)2-C6H4] (L = PPh2Me 2b, PPhMe2 2c, PMe3 2d) in essentially quantitative yields. On treatment of 1,4-Br2-C6H4 or 1-Br-4-I-C6H4 with 2 molar equivalents of n-BuLi only mono-lithiation takes place to give 1-Br-4-Li-C6H4 3 as shown through the isolation of essentially 1:1 molar equivalents of Ph2PC6H4-4-Br and Ph2PBu on treatment with 2 molar equivalents of ClPPh2. Treatment of 3, prepared by lithium/iodine exchange on 1-Br-4-I-C6H4, with [ClAu(PPh3)] affords [(Ph3P)Au(C6H4-4-Br)] 4 as expected and in addition [(Ph3P)Au(n-Bu)(C6H4-4-Br)2] 5, indicating the straightforward chloride/aryl exchange at gold may proceed in competition with oxidative addition of the n-BuI, generated in the initial lithium/iodine exchange reaction, to some aurate complex Li[Au(C6H4-4-Br)2] 6 formed in situ followed by reductive elimination of Br-C6H4-4-n-Bu in a manner that mimics lithium diorganocuprate chemistry. All of the gold-containing compounds have been spectroscopically characterised by 1H and 31P-{1H} NMR and in addition compounds 2a-d and 5 by single crystal X-ray diffraction studies. The solid state structures observed for 2a-d are dictated by non-conventional hydrogen bonding and the packing requirements of the phosphine ligands. For 2a and 2b there is no close Au...Au approach, however for 2c and 2d the reduction in the number of phenyl rings allows the formation of Au...Au contacts. For 2c and 2d the extended structures appear to be helical chains with Au...Au contact parameters of 3.855(5) A and C-Au-Au-C 104.1(3)degrees for 2c and 3.139(4) A and C-Au-Au-C -92.0(2)degrees for 2d. The Au...Au approach in 2c is longer than is normally accepted for an AuAu contact and is dictated by ligand directed non-conventional hydrogen bonding to the aurated benzene ring and the pi-stacking requirements of the phosphine ligand. By comparison of the structures 2a-2d with other structures in the database it is evident that the aurophilic interaction is a poor supramolecular synthon in the presence of non-conventional hydrogen bond donors. Searches of the CCDC database suggest that the observed parameters for the Au...Au contact in 2c sit close to the cut-off point for observing this type of contact. In addition to aurophilic contacts and non-conventional hydrogen bonds there are a number of halogenated solvent C-Cl...Au contacts observed in the structures of 2a and 2d. The nature of these contacts have implications for the accepted van der Waals radius of gold which should be extended to 2 A.