Displacement Of Halogen Research Articles

Synthesis of cyclopentane annulated δ‐lactams via diazomethane‐mediated CC bond cleavage of α‐ketoN,O‐hemiaminals

AbstractDiazomethane‐mediated C‐C bond cleavage of α‐keto N,O‐hemiaminals was investigated for the first time. Diazomethane as a reagent result C‐C bond cleavage of norbornyl α‐keto N,O‐hemiaminals, Grob‐like fragmentation, lead to the formation of cyclopentane annulated δ‐lactams in excellent yields. We have synthesized the precursor norbornyl α‐keto N,O‐hemiaminal by the nucleophilic displacement of halogen of norbornyl α‐diketone with the various amines.

Catalyst- and Base-free One-pot, Multicomponent, De Novo Assembly of Structurally Diverse Morpholine Glycoconjugates.

A catalyst-, metal- and base-free unprecedented one-pot multicomponent synthetic strategy has been established for the construction of various substituted morpholine glycoconjugates through four-component reactions of glycosyl amino alcohol, chloroacetone, acid, and isocyanides. Unexpectedly, this one-pot approach generates only the cyclized morpholine scaffolds rather than normal Ugi adduct without any external base. This reaction proceeds via in situ formations of Schiff-base followed by an intramolecular halogen displacement process, finally the Joullie-Ugi reaction takes place leading to the corresponding products with a mixture of diastereomers.

Optically active Pt-terpyridyl coordination assemblies derived from planar chiral metallothioligands

Optically active halogenated arenes containing stereogenic benzylic alcohol reacts with [CpRu(CH3CN)3][PF6] to give the major diastereomer with 90% de, in which the metal center is preferentially placed on one face of the arene ring. Thus starting with (S)-1-(2-chlorophenyl)ethanol the metal complex (pS, S)-[CpRu(HO(CH3)CH-C6H4-Cl)][PF6] (pS, S)-1 was obtained in good yield, while the (R)-alcohol provided (pR, R)-[CpRu(HO(CH3)CH-C6H4-Cl)][PF6] (pR, R)-1 metal complex. These compounds display planar and central chiralities. For comparison purposes the analogous racemic compound (rac)-[CpRu(HO(CH3)CH-C6H4-Cl)][PF6] (rac)-1 was also prepared in good yield as well. Subsequent treatment of enantiopure and racemic complexes 1 with NaSH in THF allows halogen displacement to occur at room temperature and generates the related enantiopure neutral metallothioligands of the type (pS, S)-[CpRu(HO(CH3)CH-C6H4-S)], (pS, S)-2, (pR, R)-[CpRu(HO(CH3)CH-C6H4-S)] (pR, R)-2, and (rac)-[CpRu(HO(CH3)CH-C6H4-S)] (rac)-2 (S = sulfur). These metallothioligands react rapidly with [(MeCN)Pt(terpy)][OTf]2 building blocks to give the chiral coordination assemblies [Pt(terpy)-(pS,S)-2][OTf]2 (pS,S)-3, [Pt(terpy)-(pR,R)-3][OTf]2 (pR,R)-3 and the related racemic complex (rac)-3 in which the metal-chromophore is now placed in a chiral environment. The molecular structures of (rac)-3 and the enantiopure heterobimetallic complex (pR,R)-3 were determined and show different arrangements at the supramolecular level depending on whether a homochiral or heterochiral assembly is obtained. The induced circular dichroism curves for the right-handed (pR,R)-3 and left-handed (pS,S)-3 bimetallic complexes displayed mirror image Cotton bands, confirming the enantiomeric relationship between both compounds. Our method provides an entry to the preparation of a wide range of optically pure coordination compounds with potentially important properties.

Phosphonated polyimides: Enhancement of proton conductivity at high temperatures and low humidity

A new class of highly conductive and durable polymer electrolyte membranes have been developed for fuel cell applications under elevated temperature and/or low relative humidity (RH). Highly phosphonated and fully aromatic diamine monomer was prepared via three-step high-yielding procedure from previously synthesized phosphonated bisphenol: halogen displacement of 1-fluoro-4-nitrobenzene, reducing of nitro groups, and hydrolysis of phosphonate ester groups. A series of phosphonated copolyimide ionomers with ion exchange capacity (IEC) of 2.4–4.6mequivg−1 were obtained by a typical polycondensation reaction followed by solution casting to form transparent and flexible membranes. Proton conductivity of the phosphonated membranes was comparable to that of the commercial perfluorinated ionomer at 100% RH. Typically, the conductivity value of up to 125mScm−1 was obtained for the membrane with IEC of 3.5mequivg−1 at 100°C. However, by reducing the relative humidity the merits of phosphonated polyimides became more evidence and their dry state conductivity was 1–3 order of magnitudes higher than Nafion 115 and substantially higher than the values reported for phosphonated membranes. Thermogravimetric analysis and long-term proton conductivity study of phosphonated copolyimides at high temperatures (up to 160°C) and low humidity confirmed small amount of undesired self-condensation of phosphonic acid groups compared with other phosphonated membranes.

Cellulosic polyelectrolytes: synthetic pathways to regioselectively substituted ammonium and phosphonium derivatives

Cationic polysaccharide polyelectrolytes are important synthetic targets for drug and gene delivery, especially by encapsulation of nucleic acids and proteins through electrostatic interactions. They also have potential as paracellular permeability enhancers that may increase transport across the gastrointestinal (GI) epithelium, especially for therapeutic hydrophilic macromolecules. Semisynthetic chitosan has been more heavily investigated as a cationic polysaccharide polyelectrolyte. This study explores the synthetic conditions needed to produce ammonio and phosphonio cellulose derivatives regioselectively by halogen displacement at C-6 while maximizing the degree of substitution (DS) of cationic substituent. Regioselective substitution was successful, however there were found to be some limitations to the DS and solubility of ammonium derivatives prepared in this way (highest DS 0.43); conversely, water-soluble 6-phosphonio-6-deoxycellulose derivatives were produced with DS > 0.5, with highest DS of 0.73. The repulsion between accumulating positive charges was confirmed as a likely source of DS limitation since high DS (0.9) of 6-triethylamino cellulose was synthesized under comparable conditions. Further reaction of 6-ammonio-co-6-bromo derivatives with a thiol produced 6-ammonio-co-6-thiolated products with improved aqueous solubility. The thiol DS of 0.68 determined by elemental analysis confirmed substitution of residual bromide from low DS (0.30) ammonium products to give essentially complete substitution at C-6.

Iridium-Stabilized π-Selenocyclohexadienyls: Synthesis, Molecular Structure, and Cytotoxicity

A series of iridium-stabilized selenocyclohexadienyls of general formula [Cp*Ir(η⁵-C₆H_5–nMe_nSe)][BF₄] {Cp* = η⁵-C₅Me₅, n = 0, n = 1, and n = 3} is described, with the selenocyclohexadienyl unit being isolated for the first time by π-coordination to a Cp*Ir moiety. The solid-state structure of one of [Cp*Ir(η⁵-C₆H₂Me₃Se)][BF₄] was determined by single-crystal X-ray diffraction analysis. These compounds are obtained in good yields as orange-red microcrystalline solids by halogen displacement from the related π-bonded arene-chlorinated starting materials using Na₂Se as the selenium source. Furthermore, these new compounds display relevant cytotoxic properties towards human ovarian cancer cells.

Silarylene-containing poly(ether-amide)s obtained by Yamazaki–Higashi phosphorylation technique: use of bis(4-(4-aminophenoxy)phenyl)ethylmethyl silane

Aromatic poly(ether-amide)s (PEAs) based on -(R1,R2)diphenylsilane- and oxyether units were synthesized by direct polycondensation of a diamine and two dicarboxylic acids. For this, the diamine bis(4-(4-aminophenoxy)phenyl)ethylmethylsilane was obtained by reduction of the respective dinitro compound, which was synthesized by nucleophilic aromatic halogen displacement from 1-fluoro-4-nitrobenzene with bis(4-hydroxyphenyl)ethylmethylsilane in basic medium. New silicon-containing aromatic diamine and the PEAs were characterized by elemental analysis, FT-IR, 1H, 13C and 29Si NMR spectroscopy and the results were in agreement with the proposed structures. The incorporation of aliphatic units such as methyl and/or ethyl groups on the silicon atoms affected positively the solubility of the PEAs in organic polar solvents. When their thermal and optical properties were compared with two PEAs of similar structure, containing phenyl groups bonded to the silicon atoms, it was observed a decrease of the glass transition temperature and transmittance values, maintaining a high thermal resistance.

ChemInform Abstract: An Approach to the Synthesis of Functionalized Polycyclic Aromatic Hydrocarbons.

The application of a new benzannulation reaction for the regiocontrolled synthesis of functionalized chrysenes is reported. The initial benzannulation and the subsequent halogen displacement reactions are both highly regiospecific, which thereby enables the regiocontrolled synthesis of a variety of 4,10-disubstituted chrysenes from commercially available 1,5-dihydroxynaphthalene.

An Approach to the Synthesis of Functionalized Polycyclic Aromatic Hydrocarbons.

The application of a new benzannulation reaction for the regiocontrolled synthesis of functionalized chrysenes is reported. The initial benzannulation and the subsequent halogen displacement reactions are both highly regiospecific, which thereby enables the regiocontrolled synthesis of a variety of 4,10-disubstituted chrysenes from commercially available 1,5-dihydroxynaphthalene.

Design and Synthesis of Benzimidazole-Linked meta-Substituted Benzylidenes/Benzyls as Biologically Significant New Chemical Entities

meta-Linked thiazolidinedione (TZD)– and diethyl malonate (DEM)–based benzylidenes and methyl acetoacetate (MAA)–based benzyl moieties linked to the 2-position of N-methyl benzimidazole were synthesized. TZD- and DEM-based compounds were synthesized by condensation of 2,4-thiazolidinedone and DEM respectively with the corresponding 3-substituted benzaldehyde, whereas MAA-based compounds were obtained by halogen displacement with the corresponding 3-substituted phenol. These new chemical entities were designed to provide a balanced agonism at the peroxisome proliferator activated receptor alpha/gamma (PPARα/γ) in the management of type 2 diabetes: a move from glitazones to selective PPARγ modulators (SPPARγMs). Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Fluorinated ortho-linked polyamides derived from non-coplanar 1,1′-thiobis(2-naphthol): synthesis and characterization

A novel sulfide-bridged bis(ether amine) monomer containing bulky trifluoromethyl and naphthyl substituents, 1,1′-thiobis[2-(4-amino-2-trifluoromethylphenoxy)naphthalene], was synthesized from the halogen displacement of 2-chloro-5-nitrobenzotrifluoride with 1,1′-thiobis(2-naphthol) in the presence of potassium carbonate, followed by the palladium on activated carbon-catalyzed reduction of bis(ether nitro) intermediate, 1,1′-thiobis[2-(4-nitro-2-trifluoromethylphenoxy)naphthalene], with hydrazine hydrate in refluxing ethanol. New series of fluorinated poly(ether amide)s (PEA-1–8) were synthesized from bis(ether amine) with various commercially available aromatic diacids (1–8) via a direct polycondensation method with triphenyl phosphite and pyridine. The resulting polymers had inherent viscosities, ranging from 0.61 to 0.93 dl g–1. All the polymers showed outstanding solubility and could be easily dissolved in amide-type polar aprotic solvents (for example, N-methyl-2-pyrrolidone, dimethyl sulfoxide and N,N-dimethylacetamide (DMAc)), and even dissolved in less polar solvents (for example, pyridine, tetrahydrofuran and chloroform). In addition, these polymers could be cast into transparent, flexible and tough films from DMAc solutions. The glass-transition temperatures were recorded between 209 and 251 °C, and 10% weight loss temperatures were in excess of 470 °C in nitrogen and 450 °C in air atmosphere. Moreover, these PEAs exhibited low refractive indices (n=1.5614–1.5813), birefringence (Δ=0.0055–0.0097) and dielectric constants (ɛ=2.68–2.75).

Polyamides obtained by direct polycondesation of 4-[4-[9-[4-(4-aminophenoxy)-3-methyl-phenyl] fluoren-9-YL]-2-methyl-phenoxy]aniline with dicarboxylic acids based on a diphenyl-silane moiety

Polyamides (PAs) containing fluorene, oxy-ether, and diphenyl-silane moieties in the repeating unit were synthesized in > 85% yield by direct polycondesation between a diamine and four dicarboxylic acids. Alternatively, one PA was synthesized from an acid dichloride. The diamine 4-[4-[9-[4-(4-aminophenoxy)-3-methyl-phenyl]fluoren-9-yl]-2-methyl-phenoxy]aniline (3) was obtained from the corresponding dinitro compound, which was synthesized by nucleophilic aromatic halogen displacement from p-chloronitrobenzene and 9,9-bis (4-hydroxy-3-methyl-phenyl)fluorene (1). Monomers and polymers were characterized by FTIR and 1 H, 13 C, and 29 Si-NMR spectroscopy and the results were in agreement with the proposed structures. PAs showed inherent viscosity values between 0.14 and 0.43 dL/g, indicative of low molecular weight species, probably of oligomeric nature. The glass transition temperature (T g ) values were observed in the 188-211°C range by DSC analysis. Thermal decomposition temperature (TDT 10% ) values were above 400°C due to the presence of the aromatic rings in the diamine. All PAs showed good transparency in the visible region (>88% at 400 nm) due to the incorporation of the fluorene moiety.

ChemInform Abstract: Substituted 1,2,3-Triazolo[1,5-a]quinazolines: Synthesis and Binding to Benzodiazepine and Adenosine Receptors.

This paper reports the synthesis and evaluation of the biological affinity towards benzodiazepine and A(1) and A(2A) adenosine receptors of some 3-ethoxycarbonyl or 3-phenyl-substituted 1,2, 3-triazolo[1,5-a]quinazolines. Starting from the appropriate chloro-substituted phenylazides, the series of 7 or 8 chloro-substituted triazoloquinazolines were prepared. Nitration reactions of the triazoloquinazoline ring and chlorination reactions of the hydroxyl group in the 5 position of the same ring are also reported. By nucleophilic displacement of halogen, the corresponding 5-amino derivatives and some analogous derivatives bearing cyclohexylamino and p-toluidino substituents were obtained. The binding assays showed a generalized decrease in the affinity towards the benzodiazepine receptors and confirmed a moderate affinity towards the A(1) adenosine receptors in comparison with the previously studied triazoloquinazoline derivatives.

Polyisobutylene RAFT CTA by a Click Chemistry Site Transformation Approach: Synthesis of Poly(isobutylene-b-N-isopropylacrylamide)

A novel block copolymer, composed of polyisobutylene (PIB) and poly(N-isopropylacrylamide) (PNIPAM) segments, was synthesized. The PIB block was prepared via quasiliving cationic polymerization and end-functionalized by in-situ quenching to yield telechelic halogen-terminated PIB. Azido functionality was obtained by displacement of the terminal halogen through nucleophilic substitution, which was confirmed by both 1H and 13C NMR. Coupling of an alkyne-functional chain transfer agent (CTA) to azido PIB was successfully accomplished through a copper-catalyzed click reaction. Structure of the resulting PIB-based macro-CTA was verified with 1H NMR, FTIR, and GPC, whereas coupling reaction kinetics were monitored by real-time variable temperature (VT) 1H NMR. Subsequently, the function of this macro-CTA was demonstrated by RAFT polymerization of NIPAM for synthesis of the second block. RAFT kinetics was investigated under a variety of reaction conditions using VT NMR, and the resulting block copolymers were ch...

Synthesis and Properties of Novel Fluorinated Polyamides Based on Noncoplanar Sulfoxide Containing Aromatic Bis(ether amine)

A novel sulfoxide containing bis(ether amine) monomer, 2,2′-sulfoxide-bis[4-methyl(2-trifluoromethyl)4-aminophenoxy) phenyl ether] (M2), was synthesized from the halogen displacement of 2-chloro-5-nitrobenzotrifluoride with dibenzosulfoxide (DH) in the presence of potassium carbonate, followed by catalytic reduction of bis(ether nitro) intermediate with Zinc/Ammonium chloride. A series of organic-soluble poly(ether amide)s (PA1–7) bearing sulfoxide and electronwithdrawing trifluoromethyl group were synthesized from bis(ether amine) with various aromatic diacids (1–7) via a direct polycondensation with triphenyl phosphite and pyridine. The resulting polymers had inherent viscosities ranging from 0.35 to 0.90 dL g−1 at a concentration of 0.5 g/dL in N,N-dimethylacetamide (DMAc) solvent at 25 °C. All the polymers showed outstanding solubility and could be easily dissolved in amide-type polar aprotic solvents (e.g., N-methyl-2-pyrrolidone (NMP), DMAc, and N,N-dimethylformamide) and even dissolved in less polar solvents (e.g., pyridine, and tetrahydrofuran). Also these polymers could be cast into flexible and tough films from DMAc solutions. The glass-transition temperatures of these poly(sulfoxide ether amide)s were recorded between 160–220 °C. 10% weight loss temperatures were recorded in the range of 400–505 °C in nitrogen and 380–480 °C in air atmosphere.

Substituted 3-phenylpropenoates and related analogs: electron ionization mass spectral fragmentation and density functional theory calculations

Analysis of ethyl 3-(2-chlorophenyl)propenoate by electron ionization mass spectrometry showed the distinct loss of an ortho chlorine. To characterize the structural requisites for the observed mass fragmentation, a series of 30 halogen-substituted 3-phenylpropenoate-related structures were examined. All ester-containing alkene derivatives exhibited loss of the distinctive chlorine from the 2-position of the phenyl ring. Analogous derivatives with the halogen (chlorine or bromine) in the para position did not evidence selective halogen loss. Results demonstrated that substituted 3-phenylpropenoates and their analogs fragment via the formation of a previously reported benzopyrylium intermediate. To understand the correlation between the intramolecular radical substitution and the abundance and selectivity of the chlorine (or other halogen) displacement, density functional theory calculations were performed to determine the charge on the principal cation involved in the chlorine loss (in the ortho, meta, and para positions), the charge for the neutral radical (noncation), the excess alpha-electron density on the relevant atom and the energy to form the cation from the neutral atom (ionization energy). Results showed that the selectivity and extent of halogen displacement correlated highly to the electrophilicity of the radical cation as well as the neutral radical. These data further support the proposed fragmentation mechanism involving intramolecular radical elimination.

Synthesis and Mass Spectral Studies of Some (E)- and (Z)-1-Alkylthio - and 1-Alkylsulphonyl-2-P-Tolylsulphonylstilbenes

A number of (E)- and (Z)-1-alkylthio-2-p-tolylsulphonylstilbenes (3a–i and 5a–i) were synthesized by the nucleophilic displacement of halogens with sodium salts of various alkanethiols on (E)-1-chloro-2-p-tolylsulphonylstilbene (1) and (Z)-1-bromo-2-p-tolylsulphonylstilbene (2) respectively. Oxidation of these (E) - and (Z)-1-alkylthio-2-p-tolylsulphonyl gave the corresponding (E)- and (Z)-1-alkylsulphonyl-2-p-tolylsulphonylstilbenes (4a–i and 6a–i) respectively. Mass spectral data of all the synthesized compounds were examined. Smiles-type rearrangement observed in (E)-and (Z)- sulphide-sulphones (3a–i and 5a–i) was absent in (E)- and (Z)-disulphones (4a–i and 6a–i). Loss of sulphur dioxide and sulphonyl-sulphinate rearrangement with vinyl migration was noticed in all the synthesized compounds. McLafferty-type rearrangement was observed only in (E)- sulphide-sulphones and (E)- disulphones but not in the corresponding (Z)-isomers.

Competition between Hydrogen Abstraction and Halogen Displacement in the Reaction of Br with CH3I, CH3Br, and CH3Cl

Sudden ozone depletion events in the marine boundary layer are associated with jumps in the CH3Br mixing ratio, but current models of atmospheric chemistry explain neither the ozone depletion nor the CH3Br spikes. We have used ab initio theory to predict the forward and reverse rate constants for the competing hydrogen abstraction and homolytic substitution (SH2) channels of the title reactions. Including the spin-orbit stabilization of the transition structures increases the rate constants by factors between 1.3 and 49. For the atmospherically relevant case of CH3I, our findings suggest that the hydrogen abstraction and homolytic substitution reactions are competitive. The predicted branching fraction to CH3Br is about 13%.

Ortho‐ and para‐Thioquinonoid π‐Complexes: First Synthesis, Reactivity, and Crystal Structure Determination

AbstractOvercoming a long‐standing challenge, the o‐ and p‐dithiobenzoquinone iridium complexes [Cp*Ir‐o‐(η4‐C6H4S2)] (6) and [Cp*Ir‐p‐(η4‐C6H4S2)] (7) were rationally synthesized and fully characterized for the first time including the X‐ray molecular structure of [Cp*Ir‐p‐(η4‐C6H4S2)] (7). Our strategic approach involves the preparation of the halogenated 1,2‐ and 1,4‐dichloro arene π complexes [Cp*Ir‐o‐(η6‐C6H4Cl2)][BF4]2 (4) and [Cp*Ir‐p‐(η6‐C6H4Cl2)][BF4]2 (5), which are the key molecules for 6 and 7. Subsequent treatment of 4 and 5 with NaSH and halogen displacement provides the target thioquinonoid π complexes 6 and 7 in 88 % and 95 % yields respectively. Further, the coordination chemistry of the o‐dithiobenzoquinone iridium complex [Cp*Ir‐o‐(η4‐C6H4S2)] (6) was studied by treating 6 with [(bpy)PtCl2] in the presence of AgOTf, which provided the novel platinum complex [Pt(bpy){Cp*Ir‐o‐(η4‐C6H4S2)}][OTf]2 (10) in 91 % yield. The X‐ray molecular structure of 10 is reported and shows as outstanding features the formation of 1D supramolecular assembly, which results from π–π (d = 3.484 Å; d = 3.669 Å) and Pt···Pt (d = 3.574 Å) interactions between individual subunits.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Halogen Displacement Chemistry with Silver and Alkali Metal Salts: Preparation of SF5‐Esters, Alcohols, Aliphatic Olefins, Acids and an Iodide.

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