Substitution Of Bromide Research Articles

Chemoselective Amination of 5-Bromo-2-chloro-3-fluoropyridine

The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford exclusively the bromide substitution product (2) for both secondary amines and primary anilines. A reversal in chemoselectivity is observed under neat conditions in the absence of palladium catalysis, with substitution at the 2-chloro position preferred to generate 3. Last, selective substitution of the 3-fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).

Perturbations at the chloride site during the photosynthetic oxygen-evolving cycle

Photosystem II (PSII) catalyzes the oxidation of water to O2 at the manganese-containing, oxygen-evolving complex (OEC). Photoexcitation of PSII results in the oxidation of the OEC; four sequential oxidation reactions are required for the generation and release of molecular oxygen. Therefore, with flash illumination, the OEC cycles among five Sn states. Chloride depletion inhibits O2 evolution. However, the binding site of chloride in the OEC is not known, and the role of chloride in oxygen evolution has not as yet been elucidated. We have employed reaction-induced FT-IR spectroscopy and selective flash excitation, which cycles PSII samples through the S state transitions. On the time scale employed, these FT-IR difference spectra reflect long-lived structural changes in the OEC. Bromide substitution supports oxygen evolution and was used to identify vibrational bands arising from structural changes at the chloride-binding site. Contributions to the vibrational spectrum from bromide-sensitive bands were observed on each flash. Sulfate treatment led to an elimination of oxygen evolution activity and of the FT-IR spectra assigned to the S3 to S0 (third flash) and S0 to S1 transitions (fourth flash). However, sulfate treatment changed, but did not eliminate, the FT-IR spectra obtained with the first and second flashes. Solvent isotope exchange in chloride-exchanged samples suggests flash-dependent structural changes, which alter protein dynamics during the S state cycle.

New synthesis of N-substituted benz[ g]isoquinoline-3,5,10(2 H)-triones

Various N-substituted benz[ g]isoquinoline-3,5,10(2 H)-triones 7 were prepared starting from vitamin K 3 (menadione) 9. The key steps involve substitution of a benzylic bromide by a primary amine and intramolecular condensation across the ester moiety of a (3-bromomethyl-naphth-2-yl)acetate 8 followed by oxidation with cerium(IV) ammonium nitrate (CAN) and spontaneous dehydrogenation, resulting in the title compounds 7. A selection of the synthesised new compounds was tested in vitro against Mycobacterium tuberculosis.

Nucleophilic and Electrophilic Substitutions of Difluoropropargyl Bromides.

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SN/SN‘ Competition: Selective Access to New 10-Fluoro Artemisinins

In this paper, we report a simple route to accede to a new family of C-10 fluorinated derivatives of artemisinin 7. We demonstrated that nucleophilic substitution of the allylic bromide 6 with alcohols can occur at carbon 10 (compounds 7) under solvolytic conditions (S(N)'/S(N) ratio, 87:13). Furthermore, using the particular properties of hexafluoroisopropanol (HFIP), we are able to increase the selectivity of the substitution. Primary alcohols are completely selective for allylic substitution. With amines as nucleophiles, selectivity of substitution is dependent on their nucleophilicity, but attack at carbon 16 was always favored. However, the S(N)'/S(N) ratio could be slightly increased by adding HFIP, which is able to modulate their nucleophilicity through hydrogen bonding. In preliminary in vitro assessments, these new compounds, 7, exhibited a satisfying activity against malaria.

Nucleophilic and electrophilic substitutions of difluoropropargyl bromides

Fundamental organic reactions like nucleophilic and electrophilic substitutions have seldom been studied on fluorinated propargyl or allenyl modules, when the carbon atom undergoing substitution is bonded to two fluorine atoms. Herein we report a practical synthesis of difluoropropargyl bromides from substituted acetylenes and dibromodifluorometane using a wide variety of alkyl, aryl or silyl substrates. The synthesis of O-, S- and carboxylic acid derivatives of difluoropropargyl bromide is also described. These compounds are suitable starting materials for the synthesis of electrophilically substituted difluoropropargyl derivatives via magnesium and fluoride promoted reactions. An indium-mediated reaction of silyldifluoropropargyl bromide, followed by electrophilic trapping with bromine led to a very useful bromoallene, which was then used in reactions with nucleophiles (C, O, N, P, S, Hal) to yield a de facto bimolecular nucleophilic substitution of a difluoropropargyl bromide.

Reactions of Cyclohexenyl Iodonium Tetrafluoroborate with Bromide Ion: Retardation Due to the Formation of λ3-Bromoiodane

The reaction of 4-tert-butylcyclohex-1-enyl(phenyl)iodonium tetrafluoroborate (1a) and the 4-chlorophenyl derivative (1b) with bromide ion was examined in methanol, acetonitrile, and chloroform. Products include those derived from the intermediate cyclohexenyl cation as well as 1-bromocyclohexene. Kinetic measurements show that the reaction of 1 is strongly retarded by the added bromide. The curved dependence of the observed rate constant on the bromide concentration is typical of a pre-equilibrium formation of the intermediate adduct with a fast bromide-independent reaction (solvolysis of the iodonium ion). The formation of the adduct, lambda3-bromoiodane, was also confirmed by the UV spectral change. The relative reactivity of the iodonium ion and lambda3-bromoiodane is evaluated to be on the order of 10(2). The bromide substitution product forms both via the S(N)1 reaction of the free iodonium ion and via the ligand coupling of the iodane.

Chemoenzymatic synthesis of the trans-dihydrodiol isomers of monosubstituted benzenes viaanti-benzene dioxides

Enantiopure cis-2,3-dihydrodiols, available from dioxygenase-catalysed cis-dihydroxylation of monosubstituted benzene substrates, have been used as synthetic precursors of the corresponding trans-3,4-dihydrodiols. The six-step chemoenzymatic route from cis-dihydrodiol precursors, involving acetonide, tetraol, dibromodiacetate and diepoxide intermediates, and substitution of vinyl bromide and iodide atoms, has been used in the synthesis of ten trans-dihydrododiol derivatives of substituted benzenes. The general applicability of the method has been demonstrated by its use in the synthesis of both enantiomers of the trans-1,2-and 3,4-dihydrodiol derivatives of toluene.

Synthesis of Natural Cytotoxic Camphorataimides B and C

Recently isolated camphorataanhydride A and cytotoxic camphorataimides B and C have been synthesized using chemo­selective SN2′ Grignard coupling reaction of p-methoxyphenyl­magnesium bromide with dimethyl bromomethylfumarate and chemoselective allylic substitution of bromide in bromoanhydride 9 with 2-propylmagnesium bromide as the key reactions. The present approach is general in nature and can be easily used to design the congeners of camphorataanhydrides/imides for structure-activity relationship studies.

Synthesis and characterization of ether derivatives of brominated poly(isobutylene‐co‐isoprene)

AbstractVariations of the Williamson ether synthesis were employed to prepare a range of new derivatives of brominated poly(isobutylene‐co‐isoprene) (BIIR). Unambiguous characterization of the polymeric products was accomplished by spectroscopic comparisons to low‐molecular‐weight analogues derived from brominated 2,2,4,8,8‐pentamethyl‐4‐nonene, which served as a model for the reactive functionality found within BIIR. The substitution of bromide from BIIR occurred at moderate temperatures with stoichiometric amounts of quaternary ammonium phenoxide to yield O‐alkylation products in high yields. Simple mixtures of BIIR, KOH, and aliphatic alcohols generated the desired allylic ethers when heated above 110 °C in the absence of quaternary ammonium salts. Knowledge gained from these small‐molecule alkylations was used to prepare graft copolymers from BIIR and poly(ethylene oxide) through the exploitation of the apparent ability of polyethers to activate potassium alkoxides in nucleophilic substitutions. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 983–992, 2006

Introduction of hydroxyl- or keto- functionalities in azetidin-2-ones side chain via allylic bromide rearrangement, followed by supported reagent substitution

This paper reports the allylic bromide rearrangement of 3-bromo-3-alkenyl-azetidin-2-ones, induced by m-chloroperbenzoic acid, N-bromosuccinimide or benzoylperoxide as radical initiators. The substitution of bromide by resin supported acids, followed by hydrolysis of the ester moiety, allowed an hydroxyl- or keto-function to be introduced in the C3 side chain of the azetidinone, thus giving access to a new class of potential cholesterol absorption inhibitors.

Palladium‐Catalyzed Homocoupling of Arylboronic Acids and Esters Using Fluoride in Aqueous Solvents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Facile Synthesis of Armed and Disarmed Colitose Thioglycosides

AbstractFor Abstract see ChemInform Abstract in Full Text.

Anomeric α-azido acid (2-azido-2-deoxy-hept-2-ulopyranosonic acid) derivatives en route to peptides incorporating sugar amino acids

Per- O-acylated 2,6-anhydro-aldoheptonic acids of d- glycero- d- gulo and d- glycero- l- manno configuration obtained by nitrosation of the corresponding aldonamides were transformed into methyl-, tert-butyl-, 2,2,2-trichloroethyl-, and pentachlorophenyl esters, acid chlorides and glycinamides by standard procedures. Radical-mediated bromination either by bromine in boiling CHCl 3 under illumination, or NBS in refluxing CCl 4 in the presence of Bz 2O 2 or AIBN, or Na 2S 2O 4–KBrO 3 in CH 2Cl 2–water biphasic solvent mixture at rt gave axial anomers of the 2-bromides of the above esters and acid chlorides (2-bromo-2-deoxy-α- d-hept-2-ulopyranosonic acid derivatives), while a glycinamide was split along the –H 2C–NH– bond. Anomeric bromides of the glycinamides were obtained by N-acylation of a glycine ester with the pentachlorophenyl 2-bromo-2-deoxy-ulosonates. In this reaction the axial anomeric bromide proved stable. Sodium azide in DMSO or DMF was used for the substitution of the anomeric bromides. These reactions proceeded with inversion in the case of each ester and glycinamide to produce equatorial azides (2-azido-2-deoxy-β- d-hept-2-ulopyranosonic acid derivatives). The azide substitution in 2-bromo-2-deoxy-α- d- galacto-hept-2-ulopyranosonic acid chloride gave 2-azido-2-deoxy-α- d- galacto-hept-2-ulopyranosonic acid azide with retention of the anomeric configuration. This acid azide was coupled with a glycine ester to give an axial anomeric azide. These transformations represent highly stereoselective routes to both anomers of dipeptides incorporating anomeric α-azido acids.

Quaternary ammonium elastomeric ionomers by melt-state conversion

Quaternizations of benzyl bromide units in brominated poly(isobutylene- co- p-methylstyrene), or BIMS, elastomers with tertiary amines can be readily accomplished either by solution techniques or by melt reactive mixing. At temperatures of 130 °C and above, the nucleophilic substitution of benzyl bromide with ammonium bromide occurs instantaneously in an internal mixer. The conversion is around 95% for both dimethyl alkyl and dialkyl methyl amines. Suppressions in loss tangent measured in dimethyl alkyl amine melt quaternized BIMS indicate that molecular weight amplifications as a result of ionic association in these ionomers are in line with that obtained from solution quaternized BIMS. These melt quaternized BIMS ionomers become gels when their molecular weight amplification factors are greater than 1.5. Viscosity of BIMS can be raised significantly through quaternization to facilitate its mixing with thermoplastics. BIMS ionomers can also be added into bromobutyl innerliner compounds to enhance their green strengths. The efficiency in promoting ionic associations during melt mixing of BIMS with only 0.1 mol equiv. of dimethyl alkyl amines allows residual benzyl bromide units for subsequent curing.

Methodology for the preparation of C1-monoalkylated 1,2-dihydro[C70)] derivatives: formation of the "other" regioisomer.

Deprotonation of 1,2-C(70)H(2) with TBAOH, followed by alkylation with methyl bromoacetate, results in formation of a C1-monoalkylated 1,2-dihydro-C(70) derivative. The position of the alkyl group (C1) was established by NMR spectroscopy and comparison with literature spectra of C2-monoalkylated analogs. Presumably, C1-alkylation is the major process due to selective deprotonation of 1,2-C(70)H(2) at C1. Substitution of benzyl bromide for methyl bromoacetate results in rapid dialkylation, unless the amount of base is carefully controlled, in which case C1-monobenzylation is the major process. This methodology for alkylation at C1 is complimentary to methods for the C2-monoalkylation of C(70) with Zn and methyl bromoacetate.

Substitution of a Bridgehead Bromide by Primary Organolithium Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Facile Synthesis of Armed and Disarmed Colitose Thioglycosides

Ethyl 2,4-di-O-acetyl-3,6-dideoxy-1-thio-β-l-xylo-­hexopyranoside (10) and ethyl 2,4-di-O-benzyl-3,6-dideoxy-1-thio-β-l-xylo-hexopyranoside (12) were synthesized in 60% and 55% overall yield, respectively. Starting from α-l-fucose, sequential peracetylation, anomeric bromination, nucleophilic substitution of the anomeric bromide with NaSEt and deacetylation gave ethyl 1-thio-β-l-fucopyranoside (6). Acid catalyzed regioselective cleavage of the orthoester in ethyl 2-O-acetyl-3,4-O-(1-ethoxyethylidene)-1-thio-β-l-fucopyranoside, prepared from 6, yielded the corresponding 2,4-diacetate, which was deoxygenated at C-3 to provide the disarmed thioglycoside 10. Deacetylation of 10, followed by benzyl­ation, gave armed thioglycoside 12. Several intermediates did not require purification by chromatography.

Palladium-Catalyzed Homocoupling of Arylboronic Acids and Esters Using Fluoride in Aqueous Solvents

Homocoupling of both arylboronic acids and esters has been found to proceed using catalytic amounts of Pd and stoichiometric amounts of TBAF under air atmosphere at room temperature, offering a mild and efficient protocol for the synthesis of symmetrical biaryls via C(sp 2 )-C(sp 2 ) bond formation. Aryl boronic acids bearing bromide substitution form polyphenylenes.

Substitution of a bridgehead bromide by primary organolithium reagents.

The reaction of ketone 1 with primary organolithium reagents in THF/HMPA affords not the expected carbonyl addition product but the product of bromide substitution, in reasonable yield.