Ester displacement reactions

Van Etten, R.L. Waymack, P.P. Rehkop, D.M. Transition metal ion inhibition of enzyme-catalyzed phosphate ester displacement reactions. J. Amer. Chem. Soc.. 1964, 96. 6782-6785. 

Nucleophilic displacement. - Sulphonate ester displacement reactions continue to be widely applied in amino-sugar syntheses. The precursor 18 of 3-amino-3,6-dideoxy-D-mannose was obtained from l,2 5,6-di-0-isopiopylidene-D-glucofuranose in a multi-step procedure. The procedure... 

The amount of potassium acetate which dissolves either in benzene or acetonitrile in the presence of 18-crown-6 is slightly lower than the amount of crown present. At concentrations of 0.55 and 1.0 molar crown in benzene, for example, potassium acetate is soluble to the extent of 0.4 and 0.8 molar, respectively. Similarly, in acetonitrile, 0.14M crown dissolves 0.1 equivalent of salt [19]. In the ester displacement reaction, the crown-potassium acetate ion pair must be more soluble than the crown-potassium bromide ion pair or one would expect catalyst poisoning. 

Alkyl esters of trifluoromethanesulfonic acid, commonly called triflates, have been prepared from the silver salt and an alkyl iodide, or by reaction of the anhydride with an alcohol (18,20,21). Triflates of the 1,1-dihydroperfluoroalkanols, CF2S020CH2R can be prepared by the reaction of perfluoromethanesulfonyl fluoride with the dihydroalcohol in the presence of triethylamine (22,23). Triflates are important intermediates in synthetic chemistry. They are among the best leaving groups known, so they are commonly employed in anionic displacement reactions. 

Displacement reactions with oxygen nucleophiles are of potential commercial interest. Alkaline hydrolysis provides 2-fluoro-6-hydroxypyridine [55758-32-2], a precursor to 6-fluoropyridyl phosphoms ester insecticides (410—412). Other oxygen nucleophiles such as bisphenol A and hydroquinone have been used to form aryl—pyridine copolymers (413). 

Other examples of the successful displacement of tosylates are the preparation of 31 -, 16a-,16j - and27- labeled steroids. This displacement reaction fails, however, with certain C-18 and C-19 alcohol derivatives which give mainly O—S instead of C—O bond cleavage. Unsatisfactory results were also obtained with sterically hindered tosylate esters at C-11, C-12 and C-20, which give considerable amounts of olefinic products in addition to O—S bond cleavage. ... 

Only one of these methods, namely the reaction of halides with lithium aluminum deuteride, is a true displacement reaction, following the same course as the previously discussed displacement of sulfonate esters (section Vl-A). Thus, lithium aluminum deuteride treatment of 7a- and 7jS-bromo-3 -benzoyloxy-5a-cholestanes (195) and (196) gives the corresponding deuterium labeled cholestanols (197) and (198) respectively." ... 

Various sources of fluoride ion have been investigated, of which highly nucleophilic tetraalkylammonium fluorides ate the most effective Thuf, fluoro alkyl halides and N (fluoroalkyl)amines are efficiently synthesized by treatment of the corresponding trifluoromethanesulfonic esters with tetrabutylammonium fluoride trihydrate in aprotic solvents [5fl] (equation 34) The displacement reactions proceed quantitatively at room temperature within seconds, but tail with hydrogen fluoride-pyridine and give reasonable yields only with hydrogen fluo ride-alkylamine reagents... 

Norfloxacin (41), the substance which triggered this avalanche of activity, has recently been introduced into clinical practice in the United States. Its synthesis parallels closely that of its N-methyl analogue, pefloxacin, except that the nucleophilic aromatic displacement reaction of 32 is carried out with mono-N-carboethoxypiperazine instead and the final step encompasses deblocking of this carbamoyl ester moiety [8]. 

Another deviation from the normal displacement reaction of primary tosylates occurs in nucleoside derivatives (39, 81) where cyclonucleosides and anhydronucleosides are formed by participation of a nitrogen atom (as in purine nucleosides) and oxygen atom (as in pyrimidine nucleosides ), respectively. Iodonucleosides can result from these reactions only if these cyclic compounds are prone to attack by iodide ion. Several new examples of unexpected reactions during the solvolysis of sulfonate esters in sugar derivatives have been recorded in the past few years (2, 4,5,7,15,44,62,63,94). 

Backbone (protein), 1028 Backside displacement. reaction and.363-364 von Baeyer, Adolf, 113 Baeyer strain theory, 113-114 Bakelile, structure of, 1218 Banana, esters in, 808 Barton, Derek, H. R., 389 Basal metabolic rate, 1169 Basal metabolism. 1169-1170 Base, Bronsted-Lowry, 49 Lewis, 57, 59-60 organic, 56-57 strengths of, 50-52 Base pair (DNA), 1103-1105 electrostatic potential maps of. 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Inmost instances, a haloorganic subject to either SN2 displacement reaction or SN1 substitution is heated at reflux with the trivalent phosphorus ester with the concomitant formation of the valence-expanded organophosphorus compound and haloorganic by-product, as illustrated with an example in Equation 3.1. 

Trialkyl phosphites undergo reaction with molecular halogen via a mechanism reminiscent of the Michaelis-Arbuzov reaction to form the dialkyl phosphorochloridate in good yield (Equation 4.4).7 With cyclic esters, the halogen performing the displacement reaction at carbon remains attached within the molecule. 

We note that hydrogen as well as methane, ethane and toluene have been reported [25], but do not currently have good explanations in the schemes shown above. For the methane and ethane, one would have to resort to either radical displacement reactions of the methyl ester shown in Scheme 18.3 in the middle... 

Bruice and Benkovic (1964) and Bruice (1970) have noted that conversion of a bimolecular reaction into an intramolecular reaction corresponds to a reduction in kinetic order. Comparison of reactions of varying kinetic order (Table 5) reveals that a change of 4-5kcalmole in TAS accompanies reduction in order by one. These reactions include 17 displacement reactions on phenyl esters and 4 on thiol esters with an average value of rAS /(kinetic order)... 

Glycosyl perchlorates are formed on treating glycosyl halides with silver perchlorate in inert solvents, and react readily with alcohols to give glycosides, but they have been reported to explode when heated > so their use in direct displacement reactions has understandably been limited. These esters have, however, presumably been present as intermediates in the many reactions of glycosyl halides with alcohols in which silver perchlorate was used as a catalyst (e.g. Ref. s )). 

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