Allyl Bromide Research Articles

Tert-Butoxide-Assisted Structural Transformation of 2-Aza-1,3,5-trienes: Fast Track to 5-Ethynyl-2-vinyl- and 2,5-Divinyl-1,3-thiazoles

Treatment of 2-aza-1,3,5-trienes, methyl N-[2-alkoxy-1-(prop-2-ynylsulfanyl)buta-1,3-dienyl]- and methyl N-[1-(allylsulfanyl)-2-alkoxybuta-1,3-dienyl]iminoformates, which are easily obtained from lithiated alkoxyallenes, methoxymethyl isothiocyanate, and propargyl or allyl bromide, with t-BuOK or t-BuONa in DMSO–THF results in the formation of 5-ethynyl-2-vinyl- and 2,5-divinyl-1,3-thiazoles. The reactions are realized under mild conditions at ca. –30 °C for 30 minutes. An unprecedented structural transformation of the (prop-2-ynylsulfanyl)- and (allylsulfanyl)-substituted 2-aza-1,3,5-trienes into 1,3-thiazoles presumably occurs via α-deprotonation of the substituent at the sulfur atom (on the SCH2 group) followed by intramolecular [1,5]-cyclization at the imine group and aromatization (with elimination of MeOH).

Directed Zincation or Magnesiation of 2- and 4-Pyrones and Their Derivatives

A regioselective magnesiation of the 2-pyrone scaffold was developed. Magnesiation of this heterocycle by using TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping reactions with electrophiles such as aldehydes, allylic bromides, acid chlorides, and aryl iodides provided functionalized 2-pyrones. Furthermore, methyl coumalate and 3,5-dibromo-2H-pyran-2-one were zincated by using TMPZnCl·LiCl to afford zincated heterocycles, which reacted with typical electrophiles. A second magnesiation at position C3 of the 2-pyrone scaffold was achieved by using TMPMgCl·LiCl. Also, the zincation of the 4-pyrone scaffold at position C2 is reported, leading to functionalized 4-pyrones.

Synthesis, characterization, and antitumor activity of some novel S-functionalized benzo[d]thiazole-2-thiol derivatives; regioselective coupling to the –SH group

Abstract Several 2-substituted sulfanyl benzo[d]thiazoles were regioselectively synthesized by the reaction of benzo[d]thiazole-2-thiol (1a) with a variety of reagents under different basic conditions. Some 2-(2,3-disubstituted propyl sulfanyl)benzo[d]thiazoles were obtained from 2-(allylthio)benzo[d]thiazole, which was prepared by the allylation of 1a with allyl bromide in the presence of sodium hydride in dry N,N-dimethylformamide. Reaction of 1a with various pyrazolyl-quinoxaline derivatives was also investigated. Better yields and shorter reaction time were achieved for the synthesis of some derivatives by using ultrasound irradiation. The structural elucidation of all compounds was based on both analytical and spectroscopic data. The newly synthesized compounds were tested in vitro for their antitumor activity against Ehrlich ascites carcinoma (EAC) cells grown in albino mice. Doxorubicin was used as a standard antitumor antibiotic, and some compounds showed half maximal inhibitory concentration (IC50) in the range 40–68 μg mL−1.

Threonine-Allyl-Ester and Amide of Gallic Acid Derivative as Promising Anti-HCV Inhibitors

In this study, we focused to evaluate threonine-allyl-ester (TAE) and amide of gallic acid derivative (AGA) for anti-HCV activity. The synthesis was started from esterification of commercially available Boc-L-Threonine with allyl bromide, followed by Boc deprotection with HCl/EtOAc produced threonine-allyl-ester (TAE) and amidation of the ester with the gallic acid with WSCD HCl, HOBt, and NMM produced the amide of gallic acid derivative (AGA). The synthesized were examined the antiviral activity against HCV (genotype 2a strain JFH1) and cytotoxicity against Huh7it-1. The synthesized of TAE and AGA were in ranging from 91% to 50% of yield. The TAE and AGA exhibited anti-HCV activity with a 50% effective concentration (EC50) of 24.5 μg/ml and 12.1 μg/ml without cytotoxicity, respectively. These results suggest that TAE and AGA have potential as anti-HCV. Further study, TAE and AGA are synthesized with addition another form.

(Guanidine)copper Complex-Catalyzed Enantioselective Dynamic Kinetic Allylic Alkynylation under Biphasic Condition.

Highly enantioselective allylic alkynylation of racemic bromides under biphasic condition is furnished in this report. This approach employs functionalized terminal alkynes as pro-nucleophiles and provides 6- and 7-membered cyclic 1,4-enynes with high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. Enantioretentive derivatizations highlight the synthetic utility of this transformation. Cold-spray ionization mass spectrometry (CSI-MS) and X-ray crystallography were used to identify some catalytic intermediates, which include guanidinium cuprate ion pairs and a copper-alkynide complex. A linear correlation between the enantiopurity of the catalyst and reaction product indicates the presence of a copper complex bearing a single guanidine ligand at the enantio-determining step. Further experimental and computational studies supported that the alkynylation of allylic bromide underwent an anti-SN2' pathway catalyzed by nucleophilic cuprate species. Moreover, metal-assisted racemization of allylic bromide allowed the reaction to proceed in a dynamic kinetic fashion to afford the major enantiomer in high yield.

New Method for Synthesis of Multi‐substituted Imidazoles

Here, we reported two methods for the synthesis of multi‐substituted imidazoles, firstly via four‐component cyclocondensation reaction of benzil, aliphatic amines (allylamine or pentylamine), and aromatic aldehyde and ammonium acetate. Using an ionic liquid catalyst namely, diethyl ammonium hydrogen sulfate, and under solvent‐free conditions. Secondly, via the alkylation of synthesized NH imidazoles with alkyl halide (allyl bromide and pentyl bromide) gave 8a–c in high yield (average 90%), the products can be purified by a non‐chromatographic method, and these newly synthesized compounds have been characterized by spectral data: FTIR, IR, 1H, 13C nuclear magnetic resonance, the elemental analysis, and the X‐ray structure.

Asymmetric synthesis and structure-activity studies of the fungal metabolites colletorin A, colletochlorin A and their halogenates analogues

The first asymmetric total synthesis of both enantiomers of the natural products colletorin A and colletochlorin A is presented. The proposed methodology is based on the coupling reaction between highly substituted aromatic Gilman cuprates and optically active allyl bromides, in turn obtained by Sharpless asymmetric dihydroxylation. The latter ensured a high degree of regio- and stereocontrol in the enantioselective step of the synthesis. The same synthetic strategy has been also applied for the preparation of differently halogenated synthetic analogues of colletochlorin A in high enantiomeric purity. The enantioselective synthesis of colletorin A and colletochlorin A allows to reliably assign their absolute configuration. Preliminary assessment of their herbicidal and insecticidal properties evidence the possibility to modulate the bioactivity of these compounds, highlighting its dependence on both the absolute stereochemistry and the halogen nature.

Experimental and DFT studies for the kinetics and mechanism of the pyrolysis of 2-(4-substituted-phenoxy)tetrahydro-2H-pyranes in the gas-phase

The gas-phase pyrolysis kinetics of tetrahydropyranyl phenoxy ethers: 2-(4-cyanophenoxy)tetrahydro-2H-pyran, and 2-(4-bromophenoxy)tetrahydro-2H-pyran were studied in a static system, with allyl bromide as surface-effect deactivator, and in the presence of toluene to inhibit chain reactions. The temperature and pressure were 350–440 °C and 25–89 Torr, respectively. The pyrolysis is homogeneous, unimolecular, and consistent with the first-order rate law yielding 3,4-dihydro-2H-pyran (DHP) and the corresponding 4-substituted phenol. The Arrhenius equations were found as follows:2-(4-cyanophenoxy)tetrahydro-2H-pyranlog k1 (s−1) = (14.76 ± 0.12) − (232.1 ± 1.3) kJ mol−1 (2.303 RT)−12-(4-bromophenoxy)tetrahydro-2H-pyranlog k1 (s−1) = (14.08 ± 0.15) − (209.1 ± 1.8) kJ mol−1 (2.303 RT)−1DFT theoretical calculations were performed to 2-(4-substituted-phenoxy) tetrahydro-2H-pyranes with groups H, OCH3, C(CH3)3, CN and Br. The calculated values for thermodynamic parameters using the WB97XD/6–311 + +G(d,p) level have a good agreement with the experimental values except for the cyano compound. Experimental and theoretical data suggest a mechanism with four-membered cyclic transition state (TS). The results indicate a small increment of rate constants values with raising electron donating ability groups in the phenoxy ring, and a slight decrease effect with electron withdrawing substituents. The effect of resonance structures giving by the phenyl ring seems to be the main factor in the TS stabilization. The assistance of the oxygen atom belonging to the phenoxy group in the pyranyl hydrogen abstraction exerts influence on the rate constants, but the polarization of Cδ+⋯δ−OPh bond is proposed as the rate determining process.

Generation of Aryl and Heteroaryl Magnesium Reagents in Toluene by Br/Mg or Cl/Mg Exchange.

The alkylmagnesium alkoxide sBuMgOR⋅LiOR (R=2-ethylhexyl), which was prepared as a 1.5 m solution in toluene, undergoes very fast Br/Mg exchange with aryl and heteroaryl bromides, producing aryl and heteroaryl magnesium alkoxides (ArMgOR⋅LiOR) in toluene. These Grignard reagents react with a broad range of electrophiles, including aldehydes, ketones, allyl bromides, acyl chlorides, epoxides, and aziridines, in good yields. Remarkably, the related reagent sBu2 Mg⋅2 LiOR (R=2-ethylhexyl) undergoes Cl/Mg exchange with various electron-rich aryl chlorides in toluene, producing diorganomagnesium species of type Ar2 Mg⋅2 LiOR, which react well with aldehydes and allyl bromides.

Bmim][Br] as an Inexpensive and Efficient Medium for the Barbier‐Type Allylation Reaction Using a Catalytic Amount of Indium: Mechanistic Studies

Barbier‐type allylation reactions of aldehydes and ketones have been carried out with both unsubstituted and γ‐substituted allyl bromides using only a catalytic amount (0.1 equiv.) of In metal in [bmim][Br], but not in H2O, organic solvents, or other room‐temperature ionic liquids. The reactions did not require any metal activator and proceeded chemo‐ and regioselectively. The results of time‐dependent 1H NMR studies suggested that besides acting as a solvent, [bmim][Br] also activates the In metal surface by electron polarization to generate both CH2=CHCH2–In (I) and CH2=CHCH2–InBr2 (II) from allyl bromide and In. Of the active allylating intermediates, species II was regenerated by the in situ reduction of InBr3 with an imidazolium‐based N‐heterocyclic carbene, both produced during the process, accounting for the catalytic action of the In metal.

An efficient and facile method of grafting Allyl groups to chemically resistant polyketone membranes

Polyketone is a thermoplastic polymer known for its strong mechanical properties and chemical resistance. Such superiorities make it difficult to process and chemically modify for further functionalizations and applications. In this work, we introduce a novel method for functionalizing the alpha carbon of polyketone. We succeeded to attach allyl groups to the backbone of polyketone by a heterogeneous reaction between polyketone enolate and allyl bromide. Allylated polyketone is not soluble in common solvents. Since we started with a membrane of polyketone, there is no need to cast again. Further functionalization is possible through pending allyl groups via alkene addition reactions and ionic or radicalic polymerization. FTIR, elemental analysis, solid NMR, FT-Raman, SEM and XPS methods were employed to confirm the elemental composition, molecular structure and morphology. In addition, X-ray diffractometer (XRD), UV–Visible spectroscopy and thermal analysis were used to investigate the crystal structure, physical and electronic properties.

Transition-Metal-Free Formylation of Allylzinc Reagents Leading to α-Quaternary Aldehydes.

The first example of formylation of allylzinc reagents using S-phenyl thioformate is presented. The reaction proceeded under mild conditions without any transition-metal catalyst, forming quaternary carbon centers with reactive functionalities, such as formyl and vinyl groups. Moreover, Barbier-type formylation of an allylic bromide with a sterically demanding thioformate was achieved. As a preliminary result, asymmetric formylation was conducted using a menthol-derived chiral thioformate.

Complexes of dichlorosilylene with allyl chloride and allyl bromide: matrix IR spectroscopy and quantum chemical studies

Formation of donor-acceptor complexes between dichlorosilylene, SiCl2, and allyl halides, AllHal(Hal= Cl, Br) was detected in Ar matrixes using matrix IR spectroscopy. In agreement with the predictions of the performed quantum chemical calculations, only broad unstructured absorption bands contributed by different conformers of the 1 : 1 complexes between SiCl2 and AllHal were observed in IR spectra of matrixes after deposition in the regions of characteristic vibrations of starting reactants. Annealing of matrixes resulted in strong narrowing the bands due to conversions of different conformers into the most stable structures. The predominantly formed conformers in both the reaction systems were those of complexes with SiCl2 coordinated to the Hal atoms of AllHal in the gauche conformations. At the same time, according to the calculations, the complexes with SiCl2 coordination to the double bonds of AllHal can be only slightly less stable than the complexes with coordination to the Hal atoms, and all these basic centers can be considered as comparable in their activity in the complexation. The only products revealed upon photolysis of complexes were the products of silylene insertion into the C–Hal bonds, viz., AllSiCl3 and AllSiCl2Br. Theoretical study of thermal transformations in the SiCl2 + AllHal systems showed that formal insertion of SiCl2 in the C–Hal bonds and its addition to the double bonds of AllHal have low activation barriers of 3–8 kcal mol–1. However, these barriers are too high for these reactions to occur under the matrix isolation conditions.

Bio-based polymer networks by thiol-ene photopolymerization of allylated l-glutamic acids and l-tyrosines

Triallylated l-glutamic acid and l-tyrosine (A3E amd A3Y) and their tetraallyl derivatives (A4E and A4Y) were synthesized by reactions of l-glutamic acid and l-tyrosine with allyl bromide in the presence of potassium carbonate, respectively. Thiol-ene photopolymerizations of the allylated amino acids and a pentaerythritol-based tetrathiol (S4P) at allyl/SH 1/1 in the presence of photo-initiators produced photo-cured products (pA3E-S4P, pA3Y-S4P, pA4E-S4P and pA4Y-S4P). Furthermore, thermal post-curing after photo-curing of allylated amino acid/S4P mixtures containing photo-initiators and a thermal initiator produced photo and thermal cured products (ptA3E-S4P, ptA3Y-S4P, ptA4E-S4P and ptA4Y-S4P). Although the thermally post-cured products became dark in color, all the cured films were flat and had smooth surfaces. The FT-IR analysis revealed that allyl and thiol conversions increased by the thermal post-curing for all the curing systems. The glass transition temperature (Tg), 5% weight loss temperature (Td5), tensile strength and tensile modulus of each thermally post-cured product were higher than those of the corresponding photo-cured product, reflecting the increase of crosslinking density by the thermal post-curing. Also, A4E- and A4Y-based cured products exhibited higher Tgs, Td5s, tensile strengths and moduli than the corresponding A3E- and A3Y-based cured products, respectively. Especially, ptA4Y-S4P exhibited the highest Tg (24.4 °C), Td5 (319 °C), tensile strength (18.2 MPa) and tensile modulus (1037 MPa) among all the cured products.

Stereoselective synthesis of functionalized vinyl ethers from allyl bromides activated by triethylamine

ABSTRACTAn efficient coupling reaction of allyl bromides with various alcohols as nucleophiles activated by triethylamine, leading to functionalized vinyl ethers in good yields and with full stereoselectivity.

Asymmetric Reduction of Allyl Bromides by Copper Catalysis

Key words copper catalysis - allylic reduction - hydrosilanes - allyl bromides

Redox-Active Ligand-Assisted Two-Electron Oxidative Addition to Gallium(II).

The reaction of digallane (dpp-bian)Ga-Ga(dpp-bian) (2) (dpp-bian=1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) with allyl chloride (AllCl) proceeded by a two-electron oxidative addition to afford paramagnetic complexes (dpp-bian)Ga(η1 -All)Cl (3) and (dpp-bian)(Cl)Ga-Ga(Cl)(dpp-bian) (4). Treatment of complex 4 with pyridine induced an intramolecular redox process, which resulted in the diamagnetic complex (dpp-bian)Ga(Py)Cl (5). In reaction with allyl bromide, complex 2 gave metal- and ligand-centered addition products (dpp-bian)Ga(η1 -All)Br (6) and (dpp-bian-All)(Br)Ga-Ga(Br)(dpp-bian-All) (7). The reaction of digallane 2 with Ph3 SnNCO afforded (dpp-bian)Ga(SnPh3 )2 (8) and (dpp-bian)(NCO)Ga-Ga(NCO)(dpp-bian) (9). Treatment of GaCl3 with (dpp-bian)Na in diethyl ether resulted in the formation of (dpp-bian)GaCl2 (10). Diorganylgallium derivatives (dpp-bian)GaR2 (R=Ph, 11; tBu, 14; Me, 15; Bn, 16) and (dpp-bian)Ga(η1 -All)R (R=nBu, 12; Cp, 13) were synthesized from complexes 3, 10, Bn2 GaCl, or tBu2 GaCl by salt metathesis. The salt elimination reaction between (dpp-bian)GaI2 (17) and tBuLi was accompanied by reduction of both the metal and the dpp-bian ligand, which resulted in digallane 2 as the final product. Similarly, the reaction of complex 10 with MentMgCl (Ment=menthyl) proceeded with reduction of the dpp-bian ligand to give the diamagnetic complex [(dpp-bian)GaCl2 ][Mg2 Cl3 (THF)6 ] (18). Compounds 11, 12, 13, 15, and 16 were thermally robust, whereas compound 14 decomposed when heated at reflux in toluene to give complex (dpp-bian-tBu)GatBu2 (19). Both complexes 7 and 19 contain R-substituted dpp-bian ligand: in the former compound the allyl group was attached to the imino-carbon atom, whereas in complex 19, the tBu group was situated on the naphthalene ring. Crystal structures of complexes 3, 8, 9, 10, 13, 14, 18, and 19 were determined by single-crystal X-ray analysis. The presence of dpp-bian radical anions in 3, 6, 8, and 10-16 was determined by ESR spectroscopy.

Synthesis of Chiral 1,3-Dienes through Ring-Closing Metathesis of Enantioenriched Enynes: Potential Precursors of Morphane Analogs.

A simple methodology for the synthesis of enynes by indium mediated diastereoselective allylation of aromatic N-tert-butanesulfinylimines bearing alkenyl groups at ortho-position with allyl bromide has been developed. The addition of the allyl indium intermediate to the chiral imine took place with excellent diastereoselectivity. Ruthenium-catalyzed ring-closing metathesis of the resulting enynes provided the expected cyclic 1,3-dienes in good to moderate yields. These chiral dienes are potential precursors of biologically and pharmacologically active morphane derivatives.

Copper-catalyzed oxidative multicomponent reaction: synthesis of imidazo fused heterocycles with molecular oxygen.

An oxidative cascade that involves multicomponent reaction comprising a terminal alkyne, 2-amino N-heterocycle, benzyl or allylic bromide with molecular oxygen, delivering densely functionalized imidazo fused heterocycles, is described. This reaction features a cheap catalyst, a green oxidant, and readily available starting materials, which make the overall synthesis applicable in the quick access to relevant pharmaceutical molecules with imidazole derived heterocycles.

Photocatalytic Barbier reaction - visible-light induced allylation and benzylation of aldehydes and ketones.

We report a photocatalytic version of the Barbier type reaction using readily available allyl or benzyl bromides and aromatic aldehydes or ketones as starting materials to generate allylic or benzylic alcohols. The reaction proceeds at room temperature under visible light irradiation with the organic dye 3,7-di(4-biphenyl)1-naphthalene-10-phenoxazine as a photocatalyst and DIPEA as sacrificial electron donor. The proposed cross-coupling mechanism of a ketyl- and an allyl or benzyl radical is supported by spectroscopic investigations and cyclic voltammetry measurements.