Finkelstein substitution

Finkelstein Substitutions in Acetone, DHF and Methanol. Rates and Arrhenius Parameters... 

A Finkelstein substitution with practical utility was reported some years ago (Fig. 34).130 An co-bromo fatty acid undergoes halogen exchange with radioactive Na 23i to provide the labelled iodo acid, used as a tracer for the medical exploration of cardiac metabolism. The sonochemical reaction conducted in butanone provides quantitative yields of the expensive and thermally labile product, and the presence of water in the solvent, up to 7%, is tolerated. In comparison, the usual method requires heating at ca. 180 C and anhydrous conditions, and the purity of the product is much less satisfactory. It can be noticed that the unusually high temperature of the sonochemical reaction, close to the solvent boiling point, makes an interpretation hazardous. A second case of a Finkelstein substitution, a mesylate-iodine exchange, was published recently without experimental detail. i... 

Of preparative importance is the substitution of chloride or bromide or iodide, since the more reactive alkyl iodides are better substrates for further transformations. Alkyl iodides often are difficult to prepare directly, which is why the conversion of readily accessible chlorides or bromides via a Finkelstein reaction is often preferred. 

H. Finkelstein, Ber. Dtsch. Chem. Ges. 43, 1533 (1910) J. F. Norris, R. Thomas and B. M. Brown, ibid. 43, 2940 (1910). See also J. Schmidlin and R. v. Escher, ibid. 43, 1153 (1910). The resultant dichlortetraphenyl-ethane decomposes easily, mainly with the liberation of HC1 and the formation of tetraphenylethylene with Cl substituted in the para position in one of the phenyl groups. 

Fig. 5 Marcus plot of electron transfer reductions of alkyl halides, as contrasted with archetypal SN2 substitution processes (Finkelstein reactions, circled see Eberson,...

One of these consists in the substitution of iodine for the ester group attached to the primary carbon atom as the result of prolonged heating with sodium iodide in acetone solution (Finkelstein s reagent (20]). The reaction appears likely to consist in breaking the C—O linkage ... 

The resulting homoallylic alcohol 24 is next transformed into a tosylate, which subsequently undergoes nucleophilic substitution with sodium iodide in a Finkelstein reaction to give compound 13. 

Willow-like cascade construction was facilitated by the preparation of the AB2-type building blocks, e.g., 6-bromo-l-(4-hydroxy-4 -biphenylyl)-2-(4-hydroxyphenyl)hexane (40 Scheme 6.12), 13-bromo-l-(4-hydroxyphenyl)-2-[4-(6-hydroxy-2-naphthalenylyl)-phenyljtridecane (41), and 13-bromo-l-(4-hydroxyphenyl)-2-(4-hydroxy-4"-p-terpheny-lyl)tridecane (42). Scheme 6.12 illustrates the monomer preparative strategy for the incorporation of the monomeric mesogenic moieties predicated on conformational (gauche versus anti) isomerism. Thus, one equivalent of 4-hydroxybiphenyl was allowed to react with 1,4-dibromobutane to yield the monobromide 43, which was converted under Finkelstein conditions to the corresponding iodide 44. Treatment of the latter with ketone 45 under phase transfer conditions afforded the a-substituted ketone 46. Reduc-... 

Azaphosphoranium salts 39 have been used as phase-transfer catalysts for the Finkelstein and Kolbe reactions (substitution of halogen in alkyl halides by iodide and cyanide, respectively) (78PS145). Representatives of... 

Ammonium salts with two different alkyl chains were prepared directly via subsequent alkylations of dimethylamine with primary bromides and crystallization. Commercial hexadecyl-methylamine can be conveniently applied in the same way in order to convey functionality to cationic synkinons. A recent example describes subsequent alkylations with a small functional and a long-chain primary bromide (Scheme 2.4). A-acylated / -phenylenediamine was also alkylated at the second nitrogen atom which had two different alkyl chains, with or without extra functionality . After deacylation, this head group can be diazotized or coupled oxidatively with various heterocycles in water (Scheme 2.4). Photoactive and coloured membrane surfaces are thus obtained. Phenylene-diamine, pyridine and in particular A-methyl-4,4-bipyridinium chloride are relatively weak nucleophiles. Substitution of bromides is slow and the more reactive iodides can rarely be obtained commercially, but the selection of nitromethanes as solvent for bromide substitution is of great help as well as the addition of sodium iodide to enforce a Finkelstein reaction or a combination of both. 

Halide exchange from the lower halides to iodine is often desirable due to the higher reactivity of iodides in nucleophilic substitutions, reductions, organometallic or radical reactions (Scheme 30). Conversion of chlorides and bromides to iodides with sodium iodide in acetone is called the Finkelstein reaction. This halide exchange is an equilibrium process, which is shifted to the iodinated products due to precipitation of the less soluble sodium bromide or chloride from acetone. Best results are obtained when the reaction mixture is free of water. 

Hayami, J., Koyanagi, T., Hihara, N., Kaji, A. Substrate-nucleophile association in the Finkelstein reaction system in a dipolar aprotic solvent. Formation of complex between substituted chloromethanes and halide ion in acetonitrile. Bull. Chem. Soc. Jpn. 1978, 51, 891-896. 

The fact that fluoride is a poor leaving group in aliphatic nucleophilic substitutions and the high volatility of fluoroaliphatic compounds are the keys to the Finkelstein synthesis of alkyl fluorides. An alkyl iodide, bromide, or tosylate is heated in a polar solvent vith an alkali fluoride and the volatile alkyl fluoride is removed by distillation during the reaction [30] (Scheme 2.11). For safe handling of primary alkyl fluorides it must be kept in mind that the even-membered compounds of this series are toxic, because they can be oxidatively metabolized to the poisonous fluoroacetate [31]. 

S30a. Smith, H. W., Finkelstein, N., Alininosa, L., Crawford, B., and Graber, M., The renal clearance of substituted hippuric acid derivatives and other aromatic acids in dog and mean. J. Clin. Invest. 24, 388-404 (1945). 

Ross and Finkelstein (1957), Ross and Petersen (1958), Ross (1958), Ross et al. (1959), Suarez (1961) and Greizenstein and Brieux (1962) have found other reactions which are subject to general base catalysis. Ross and co-workers investigated the substitution reactions of 1-chloro-... 

Chlorination. TMSCl has been used as the chloride source in a variety of substitution reactions. For example, when 1-bromoundecane is heated with stoichiometric amount of TMSCl in DMF at 90 °C and in the presence of imidazole, a Finkelstein-like reaction provides the corresponding 1-chloroundecane in quantitative yield (eq 51). ... 

This reaction was initially reported by Finkelstein in 1910. It is a preparation of alkyl iodide from alkyl bromide or chloride with potassium or sodium iodide in acetone. Therefore, this reaction is generally known as the Finkelstein reaction. Occasionally, it is also referred to as the Finkelstein halide exchange, Finkelstein displacement, or Conant-Finkelstein reaction. Mechanistically, this reaction is a simple nucleophilic substitution (often via Sn2), as iodide is a stronger nucleophile than bromide or chloride. The yield of this reaction is very high and can be quantitative if occurs in DMF. It was found that the trifluoromethyl group retards the displacement of bromide when it presents as an a- or /3-substituent but accelerates the reaction as a substituent in an allylic chloride. Under normal conditions, this type of halide displacement does not occur for aryl halides. For dihalides, unsaturated or cyclic compounds may form via carbocation intermediates, which form transient covalent iodides or are reduced directly by iodide to free radicals. However, the aromatic halide exchange reacts smoothly when 10% Cul is present in the reaction... 

B Chenera, JA Finkelstein, DF Veber. Protodetachable arylsilane polymer linkages for use in solid phase organic synthesis. J Am Chem Soc 117 11999-12000, 1995. Y Han, SD Walker, RN Young. Silicon directed ipso-substitution of polymer bound arylsilanes preparation of biaryls via the Suzuki cross-coupling reaction. Tetrahedron Lett 37 2703-2706, 1996. 

Nucleophilic aliphatic substitution, as defined by (1), and typified in organic chemistry by the Finkelstein and Menschutkin reactions, can extend into inorganic chemistry with the inclusion of metal complexes which are sufficiently nucleophilic. The aim of this review is to collect the somewhat... 

As expected for a Finkelstein reaction, phase-transferred halide ions behave as bases as well as nucleophiles. Bromocyclohexane is reported to react with 18-crown-6 activated potassium fluoride to quantitatively yield cyclohexene [2]. The corresponding reaction of chlorocyclohexane in which fluoride ion is associated with a resin-bound quaternary ion yields only 50% cyclohexene [5]. Quantitative alkene formation is observed, however, when sec-octyl bromide is treated with potassium fluoride in the presence of hexadecyltributylphosphonium ion [1]. A more complicated situation is encountered in the reaction of 2-chloro-2-methylcyclohexanone with fluoride ion. In this case, a mixture of elimination and substitution products is obtained (69% and 31% respectively, see Eq. 9.2) [2]. The elimination reactions of phase-transferred halide ions are included in Table 9.1. 

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