39. Aliphatic substitution and the Walden inversion. Part III. Comparison, using radioactive bromine, of the rates of inversion and substitution in the reaction of bromide ions with α-bromopropionic acid

Cowdrey, W. A.; Hughes, E. D.; Nevell, T. P.; Wilson, Christopher L.

doi:10.1039/jr9380000209

Cited by 11 publications

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“…The phenomenon has been observed also in the reactions of quaternary ammonium salts with hydroxide (520) and with acetate (581) ions. Among the many examples of displacement accompanied by configurational inversion at the reacting center in polyfunctional compounds are the reactions of a-halo acids and esters with halide ion (169,495,497,698) and the ring-opening reactions of ethylene oxides (290).…”

Section: The Direct Displacement Reaction a Kinetics And Stereochemimentioning

confidence: 99%

Solvolytic Displacement Reactions At Saturated Carbon Atoms

1956

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Section: The Direct Displacement Reaction a Kinetics And Stereochemimentioning

confidence: 99%

Solvolytic Displacement Reactions At Saturated Carbon Atoms

1956

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“…In other words, this primary intermediate does not undergo pseudorotation-a process which changes the relative positions of substituents in trigonal bipyramid without the bond around the heteroatom breaking, and influences the stereochemical outcome of a substitution. In a similar way, Hughes et al showed that stereospecific inversion occurs in the symmetric bromide exchange at carbon in optically active α-phenylethyl bromide [2] and α-bromopropionic acid [3]. The Walden inversion, observed in these halogen-halogen exchange reactions at carbon was best rationalized in terms of the classical, concerted S N 2 mechanism with a single TS.…”

Section: Introductionmentioning

confidence: 89%

“…In 1935, the research group of Hughes [1] provided a direct proof of the Walden inversion by demonstration that the rate of the exchange (kexch) between radioactive iodide anion (*I − ) and optically active d-sec-octyl iodide is equal to the rate of inversion, e.g., to half the rate of racemization (krac) (Scheme 2). In a similar way, Hughes et al showed that stereospecific inversion occurs in the symmetric bromide exchange at carbon in optically active α-phenylethyl bromide [2] and α-bromopropionic acid [3]. The Walden inversion, observed in these halogen-halogen exchange reactions at carbon was best rationalized in terms of the classical, concerted SN2 mechanism with a single TS.…”

Section: Introductionmentioning

confidence: 89%

“…The authors investigated the symmetrical exchange of the methoxyl ion at P in methyl ethylphenylphosphinate 1. Taking advantage of the method of Hughes [1][2][3] discussed above, they determined the rate of racemization (krac) of the optically active methyl phosphinate 1 by the methoxide ion and compared this with the rate of exchange (kexch) of the [ 14 C]methoxyl group in the radioactive ester 1* (Scheme 5). Being stimulated by these results, we turned our attention to the other identity substitution reactions at heteroatoms (P, S) published so far in the literature.…”

Section: Stereochemistry and Mechanism Of Identity Methoxy Exchange Reaction In Methyl Ethylphenylphosphinatementioning

confidence: 99%

“…The authors investigated the symmetrical exchange of the methoxyl ion at P in methyl ethylphenylphosphinate 1. Taking advantage of the method of Hughes [1][2][3] discussed above, they determined the rate of racemization (krac) of the optically active methyl phosphinate 1 by the methoxide ion and compared this with the rate of exchange (kexch) of the [ 14 C]methoxyl group in the radioactive ester 1* (Scheme 5). As the pseudo-unimolecular rate of racemization of the optically active 1 has been found to be twice as large as the rate of the methoxyl exchange, the kinetic measurements provided a direct evidence that each elementary substitution step in this reaction occurs with inversion of configuration at phosphorus.…”

Section: Stereochemistry and Mechanism Of Identity Methoxy Exchange Reaction In Methyl Ethylphenylphosphinatementioning

confidence: 99%

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Nucleophilic Substitution at Heteroatoms—Identity Substitution Reactions at Phosphorus and Sulfur Centers: Do They Proceed in a Concerted (SN2) or Stepwise (A–E) Way?

et al. 2022

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The mechanisms of three selected identity substitution reactions at phosphorus and sulfur occurring with stereospecific inversion have been investigated using density functional theory (DFT). The first identity reaction between methoxyl anion and methyl ethylphenylphosphinate 1 reported in 1963 has been shown to proceed in a stepwise fashion according to the addition–elimination (A–E) mechanism involving formation of a pentacoordinate phosphorus intermediate (TBI-1). In contrast, the results of DFT studies of the identity chloride exchange reaction in (ethoxy)ethylphosphonochloridothionate 3 in acetone solution provided evidence that it proceeds synchronously according to the classical Ingold’s SN2-P mechanism. DFT calculations of the methoxyl–methoxy exchange reaction at sulfur in methyl p-toluenesulfinate 4 catalyzed by trifluoroacetic acid in methanol revealed that it proceeds stepwise (A–E mechanism), involving the formation of the high-coordinate sulfurane intermediate. In both identity transesterification reactions, 1 and 4, the transiently formed trigonal bipyramidal intermediates with the two methoxyl groups occupying apical positions (TBI-1 and TBI-4) have higher free energy barriers for the Berry-type pseudorotation than those for direct decomposition to starting phosphinate and sulfinate ensuring stereospecific inversion of configuration at the phosphinyl and sulfinyl centers. Thus, the DFT method proved its usefulness in the distinction between both mechanisms that are often indistinguishable by kinetic measurements.

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Synthesis of the 2‐ethyl‐3‐methylsuccinic acidsviaa stereospecific malonic ester alkylation

Leeuwen

Noordam

Maat

et al. 1980

Recl. Trav. Chim. Pays‐Bas

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Synthesis of the 2-ethyl-3-nzethylsuccinic acids0-and p-Halogenoanilines Slarlinq from 0-or p-arsanilic acid'. Recrystallized arsanilic acid (30 mg) was dissolved in 1 ml of 7.2 N H,S04. After addition of the 1311 or the '"At activity and 5 mg of K1 the reaction mixture was heated at 60°C for 30 min. After cooling to OOC, 1 ml of diethyl ether was added and under vigorous stirring of the solution the pH was brought to 11.5 by addition of solid Na,CO,. The aniline were purified on SiO, with CH,CI, as eluent.Starring from (ch1oromercuri)anilines. This reaction is described elsewhere in detail'. m-Halogenoaniline m-(Ch1oromercuri)nitrobenzene was prepared as described by Klapprofh et al.'. To a suspension of 10 mg of this compound in 1 ml of 0.4 N H,SO,, 5 PI of 1 M K1, together with the 13'1 or 'llAt activity were added and the reaction mixture was stirred for 30 minutes. The precipitated Hgl, was dissolved by addition of an excess of K1. The halogenonitrobenzene was extracted with CH,CI, and the CH,Cl, layer was washed with a 1 mM aqueous Na,SO, solution. After removal of the CH,CI, in uacw the residue was dissolved in 2 ml of 6 N HCI and 15 mg of SnC1,.2 H,O were added. The reaction mixture was heated to 55OC for 2 h and subsequently cooled to 0°C. Diethyl ether (2 ml) was added and under vigorous stirring the pH of the solution was brought to 11.5 by addition of Na,CO,. The ethereal layer was separated and washed with aqueous Na,SO, and chromatographed on SiO, (eluent CH,CI,). 0-and p-HalogenophenolsA mixture of 0-and p-(ch1oromercuri)phenols was prepared as described by Dimrorh". These compounds were converted into the corresponding halogenophenols as described earlier'. The phenols were isolated by chromatography on SiO, (eluent CH,CI,). m-Halogenophenol m-Astatoaniline (or ['311]-tn-iodoaniline) was diazotized in 2 ml of 0.4 N H,SO, at -5°C with NaNO, (3 mg). After stirring for 30 minutes the excess NaNO, was destroyed by addition of urea. Heptane (2 ml) was added and under vigorous stirring the reaction mixture was slowly heated to 45OC and kept at this temperature for 2 h. The heptane layer was isolated and washed with a Na,SO, solution and chromatographed on SiO, (eluent CH,CI,). 5-HalogenouracilThe halogenouracil was synthesized from the 5-chloromercuri derivative as described elsewhere*. The product was isolated by chromatography on SiO, using the organic phase of a mixture of benzeneln-butanollwater (5/3/4) as eluent. pK, measurementsThe ?"At or 1311 compound was dissolved in heptane (except for the halogenouracils, which were dissolved in benzene). Two ml of this solution was thoroughly shaken at 0°C with 2 ml of an aqueous buffer of different pH values (in steps of 0.1-0.25 pH units). After standing at 0°C for $ h 1 ml of each layer was pipetted quickly and counted. Each p& measurement was carried out at least six times. The following buffer systems were used: halogenobenzoic acids citrate buffer pH 2-45 halogenoanilines citrate buffer pH 2.24.9 halogenophenols borax buffer pH 8.0-9.0 halogenouracils ...

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39. Aliphatic substitution and the Walden inversion. Part III. Comparison, using radioactive bromine, of the rates of inversion and substitution in the reaction of bromide ions with α-bromopropionic acid

Cited by 11 publications

References 0 publications

Solvolytic Displacement Reactions At Saturated Carbon Atoms

Solvolytic Displacement Reactions At Saturated Carbon Atoms

Nucleophilic Substitution at Heteroatoms—Identity Substitution Reactions at Phosphorus and Sulfur Centers: Do They Proceed in a Concerted (SN2) or Stepwise (A–E) Way?

Synthesis of the 2‐ethyl‐3‐methylsuccinic acidsviaa stereospecific malonic ester alkylation

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