Finkelstein Reaction Research Articles

Studies on the α-acetylation of δ-valerolactone and ε-caprolactone

The synthetic approach to α-acetylated δ-valero- ( 7a ) and ε-caprolactone ( 7b ) is reported. While 7a was isolated in 21% yield from the respective iodoester 5a by an alkylation sequence involving transesterification and Finkelstein reaction, 7b was not obtained from 5b but the dimer 8 . Also transesterification and olefin ring closing metathesis (RCM) failed to prepare 7b . RCM resulted in the dimeric lactone 10 , showing that the formation of 14-membered rings is favored over that of seven-membered rings. A Mukaiyama-type Claisen reaction finally gave α-acetyl lactones 7a and 7b in practically useful quantity of about 10 g (62% yield): starting lactones 13a, b were converted to silylenolethers 14a, b , which were acetylated with acetic anhydride in presence of the Lewis acid catalyst TiCl 4. However, acetylation depends on the addition sequence of starting materials: if the mixture of Ac 2O/TiCl 4 is added to 14b , lactone 7b can be further converted to give bis-oxepanonyl ethanols 15a, b . Both compounds 15 were characterized by X-ray crystallography and NMR.

Synthesis of 3‐Alkylcarbonyloxymethyl Derivatives of 5‐Fluorouracil.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 3‐alkylcarbonyloxymethyl derivatives of 5‐fluorouracil

Abstract3‐Alkylcarbonyloxymethyl derivatives of 5‐fluorouracil have been synthesized starting with 1‐ethyloxy‐carbonyl‐5‐fluorouracil. Alkylation of the starting material with alkylcarbonyloxymethyl iodides, generated from the corresponding chlorides by the Finkelstein reaction, in the presence of 1,8‐bis(dimethyl‐amino)naphthalene followed by deprotection with 1,1‐dimethylethylamine gave good yields (50‐60%) of the target derivatives after column chromatography. A 90% yield of 3‐acetyloxymethyl‐5‐fluorouracil was obtained when the corresponding commercially available bromide was used, instead of the in situ generated iodide, and the product could be isolated from the crude reaction by crystallization. An alternate path of sequential alkylation of 5‐fluorouracil with alkylcarbonyloxymethyl chlorides in the presence of tertiary amines, exhibiting different reactivities towards the chlorides, gave an excellent yield of 1‐acetyloxymethyl‐3‐propionyloxymethyl‐5‐fluorouracil in the one instance it was attempted, but subsequent deprotection of the 1‐position with methylamine gave only a 24% yield of 3‐propionyloxymethyl‐5‐fluorouracil.

Direct synthesis of polyfluorinated allyl halides from fluoroolefins and AlX 3 (X = Cl, Br)

Reaction of (perfluoro -i-propyl)ethylene with aluminum chloride or bromide results in formation of (CF 3) 2CCHCH 2X (X=Cl or Br) in 50–65%yield. Both compounds were converted into corresponding iodide under conditions of Finkelstein reaction. Olefins (CF 3) 2CCHCH 2X readily undergo isomerization into (CF 3) 2CHCHCHX under action of triethylamine.

Looking for a contribution of the non-equilibrium solvent polarization to the activation barrier of theSN2 reaction

The solvent effect on the activation free energy of the Finkelstein reaction between methyl iodide and Cl− ions was analysed in terms of the recent Marcus theory unifying the SN2 and the electron transfer reactions. The homolytic bond dissociation energy and the related resonance energy of interaction of the states seem to be almost solvent independent. The sum of the work term wr and the solvent reorganization energy λ0/4 depends strongly on the solvent acidity parameter, e.g. ETN, describing the solvation/desolvation of anions. However, after removing the contribution of the specific solvation the linear increase of the remaining part of λ0/4 with the Pekar factor, describing the non-equilibrium solvent polarization, was observed for six aprotic solvents. Copyright © 2002 John Wiley & Sons, Ltd.

Parallel Synthesis of Alkyl Tetrazole Derivatives Using Solid Support Chemistry.

The synthesis of several omega-chloroalkyl tetrazoles and their subsequent attachment to a solid support is described. Using an in situ Finkelstein reaction, a variety of nucleophiles were alkylated and then cleaved from the resin to give pure alkyl tetrazole derivatives. A sample library of 5 x 6 demonstrates the general utility of this sequence.

理論計算による有機溶液反応過程の解析

Computational methods of organic reactions in solution are reviewed. The results of a series of molecular orbital calculations of the Wittig reaction are presented as an example which shows how the molecular orbital calculation is used to analyze the reaction and why computations of solvent effect are required. The theoretical bases of recently developed methods, including the supermolecule method, molecular simulation (Monte Carlo and molecular dynamics methods), QM/MM, RISM-SCF, and dielectric continuum model, are described with the stress on the applicability and limitation of the methods. The calculated results on several reactions such as solvolysis, the Finkelstein reaction and the Menschutkin reaction are presented.

Efficient preparation of E- β-iodovinyl phenylsulfone by Finkelstein reaction at a vinylic center

Treatment of E- β-chlorovinyl phenylsulfone, a crystalline compound that can be conveniently prepared on a large scale from 1,1,2-trichloroethane, by sodium iodide in acetone at ca 130 °C, in a sealed vessel, affords the title iodosulfone in good yield.

Quantitative reaction kinetics in the liquid state by in situ XAFS

By quantitative evaluation of in situ recorded Br K-edge XAFS spectra we obtained kinetic parameters for the halogen exchange in 2-bromopropane with sodium iodide (‘Finkelstein reaction’). The results compare well with the classical data by Ingold and co-workers. Thus, XAFS is a suitable method to quantitatively monitor reactions in the liquid state.

Applications of microwave-accelerated organic synthesis

A comparison of microwave vs conventional heating is presented for a variety of Diels-Alder reactions, ortho-Claisen rearrangements, ene reactions, alkyl bromide preparations, Finkelstein reactions, oxidations, esterifications, hydrolyses, Williamson ether syntheses and other common organic transformations. In general, microwave-promoted reactions proceed with significant decreases in reaction times and in comparable chemical yield.

Development and Application of a Continuous Microwave Reactor for Organic Synthesis

A laboratory-scale continuous microwave reactor (CMR) he been developed and used to conduct organic syntheses routinely, rapidly, and safely in a range of solvents, under pressures up to 1400 kPa and at temperatures up to 200 o C. Advantages and applications of the CMR are discussed, along with the rationale for the design. Reactions carried out with the CMR included nucleophilic substitution, addition, esterification, transesterification, acetalization, amidation, base- and acid-catalyzed hydrolysis, isomerization, decarboxylation, and elimination. Name reactions included the Michael addition, Hofmann degradation, Williamson ether synthesis, and the Mannich, Finkelstein, Baylis-Hillman, and Knoevenagel reactions

A Formal Total Synthesis of the ACE Inhibitor K-13. An Application of Arene-Ruthenium Chemistry to Complex Chemical Synthesis

Stoichiometric ruthenium activation of 4-chlorophenylalanine derivatives toward nucleophilic substitution, using phenoxide nucleophiles that are derived from protected dipeptides, allowed the formation of isodityrosine derivatives that are synthetic precursors to the ACE inhibitor K-13. An evaluation of carboxyl blocking groups revealed that a 2-bromoethyl ester is the most useful in terms of its compatibility with ruthenium complexation and subsequent nucleophile addition but that its removal is problematic. Conversion to iodoethyl ester using Finkelstein reaction conditions, in the presence of the peptide and amino acid functionality, provided a solution to this problem, since the iodoethyl group was easily removed on treatment with samarium diiodide

Studies on Synthesis and Properties of Surfactants with Specific Functions

Novel surfactants with specific functions were sinthesized from inexpensive, commercially available bulk chemicals by convenient synthetic methods. All were characterized by features such as chemical degradability, catalitic activity for a halide displacement reaction (Finkelstein reaction), ability to disperse lime soap and complex with alkali metal cations. Applications for emulsion polimerization, surface-active properties, stability constants of complexes with alkali metal ions, and solubilization of alkali metal picrates in organic solvents were studies.

Reactivity of Interstitial Cl− Anions in Synthetic Hydrotalcite-Like Materials in the Halide Exchange Reaction with Alkyl Halides

ABSTRACTTwo types of synthetic hydrotalcite-like [Mg6Al2(OH)16 ][An−%D;2/n (HT) were prepared where A = Cl− anions (Cl-HT), and NiC42− complex anions (NiCl-HT), in order to examine: (1) the reactivity of Cl− anion (or ligand) towards alkyl halides and (2) their catalytic behavior in the Finkelstein reaction. For instance, 0.4 g of NiCl-HT (Cl−: 1.41 mmol) suspended in 20 cm3 of toluene with 14.1 mmol of butyl bromide at 373 K yielded 42 % butyl chloride after 15 min of reaction. In comparison, NiCl4(Et4N)2 (precursor to prepare NiCl-HT) yielded at the same conditions only 2.4 % of butyl chloride. This indicates a great mobility of Cl− in the interlayer region of HTs. The reaction rate is greatly accelerated using DMF instead of toluene and butanol totally suppressed it. This is consistent with a SN2 mechanism. The halide-exchange reaction between benzyl chloride and butyl bromide is catalyzed by both Cl-HT and NiCl-HT.

ChemInform Abstract: Finkelstein Reaction with Aqueous Hydrogen Halides Efficiently Catalyzed by Lipophilic Quarternary Onium Salts.

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Finkelstein reaction with aqueous hydrogen halides efficiently catalysed by lipophilic quarternary onium salts

The rate of halogen metathesis between halogenoalkanes RX 1-4(X = F, Cl, Br, I) and aqueous concentrated hydrogen halides HY (Y = Cl, Br, I) is strongly accelerated under phase-transfer catalysis conditions, without solvent. The amount and nature of the nucleophilic species in the organic phase were determined.

Silver-assisted reactions of organotin oxides. A mild, neutral and anhydrous one-step conversion of primary organic halides to alcohols

Bis(tributyltin)oxide acts as a mild and neutral oxygen transfer agent in converting primary organic iodides and bromides into alcohols in good to excellent yields. The less reactive chlorides can be converted into alcohols when they are first transformed into bromides or iodides using the Finkelstein reaction. Silver salts are required for this one step conversion.

Kinetic Study of the Substitution Reactions of Benzyl Halides and Halide Ions in Acetone

AbstractThe kinetics of the Finkelstein reactions of benzyl halides and halide ions in dry acetone was studied by using the GC and HPLC methods. The method of conductivity is used to measure the degree of dissociation of alkali halide in acetone. The dissociation of the salt and the common‐ion effect were used to correct the halide ion concentration. Let kxx′‐ and Kxx′‐ represent the corrected second‐order rate constant and equilibrium constant for the PhCH2X‐X′‐ reaction, respectively, then at 25° kxx‐−= 1.83x×10−3 M−1 s−1, KII‐=4.48×104, kBrcl‐=0.377 M−1 s−1, KBrcl‐=874; and kBr‐=7.88 M−1 s−1, KIBr‐=19.2. The entropy of activation is always negative which implies that the activated complex is more solvated than the reactants. There is a good correlation between the enthalpy of activation and the C‐X bond energy. The enthalpy of activation is much smaller than the corresponding C‐X bond energy which implies that both the bond formation and the bond dissociation are taking place simultaneously in the transition state. A modified Taft equation is used to correlate the Finkelstein reactions of alkyl halides (RCH2X). However, the benzyl halides can not be fit by the correlation equation due to the strong electrical polar effects. Discussion of the Finkelstein reactions of organic halides in terms of rate constants, equilibrium constants, solvent effects, and the thermodynamic parameters is also presented.

Synthesis of [ 11C]iodomethylcyclopropane, an interesting alkylating reagent

The synthesis of [ 11C]iodomethylcyclopropane by a four-step procedure, starting from [ 11C]carbon dioxide, is presented. The [ 11 carbon dioxide was trapped in a solution of cyclopropylmagnesium bromide and the acid was reduced to give the alcoholate. When treated with p-toluenesulphonyl bromide, [ 11C]bromomethylcyclopropane was formed directly and then converted to the corresponding iodide by the Finkelstein reaction. [ 11C]Iodomethylcyclopropane was prepared in about 13% radiochemical yield (decay-corrected) and 80% radiochemical purity, with a reaction time of 20 min and a specific radioactivity in the order of 10–100 mCi/μmol.

Solvent Properties of Dichloromethane. 1. The Reactivity of Dichloromethane toward Some Ionic Nucleophiles. Dichloromethane as Solvent for Finkelstein Reactions.

Solvent Properties of Dichloromethane. 1. The Reactivity of Dichloromethane toward Some Ionic Nucleophiles. Dichloromethane as Solvent for Finkelstein Reactions.