Nucleophilic displacement reactions inversion

H-Azepine, 2-allyloxytetrahydro-Claisen rearrangement, 7, 508 3H-Azepine, 2-amino-acylation, 7, 511 effect of acidification, 7, 510 nucleophilic displacement reactions, 7, 514 synthesis, 7, 533, 535 3H-Azepine, 2-amino-7-bromo-synthesis, 7, 529 3H-Azepine, 2-anilino-ring inversion, 7, 495-499 structure, 7, 533... 

Thus solvolysis of (+)C6HsCHMeCl, which can form a stabilised benzyl type carbocation (cf. p. 84), leads to 98% racemisation while (+)C6H13CHMeCl, where no comparable stabilisation can occur, leads to only 34% racemisation. Solvolysis of ( + )C6H5CHMeCl in 80 % acetone/20 % water leads to 98 % racemisation (above), but in the more nucleophilic water alone to only 80% racemisation. The same general considerations apply to nucleophilic displacement reactions by Nu as to solvolysis, except that R may persist a little further along the sequence because part at least of the solvent envelope has to be stripped away before Nu can get at R . It is important to notice that racemisation is clearly very much less of a stereochemical requirement for S l reactions than inversion was for SN2. 

Several different nucleophilic displacement reactions of ring substituents were utilized in the synthesis of 3-azido-oxetane-2-carboxylates (Scheme 12) <2001TL4247>. The triflate ester 66, prepared from the corresponding trans-/3-hydroxy ester and triflic anhydride, was displaced by reaction with sodium azide, and inversion of configuration, to... 

All of these experiments strongly indicate that the alkaline hydrolysis of the sugar orthoacetates is a nucleophilic displacement reaction. Any one of the three carbon atoms of the five-membered ring may be attacked. Since the hydroxyl ion must approach the tetrahedron of the attacked carbon atom in the direction of the center of the face opposite the vertex occupied by the group to be displaced, it is evident that the reaction must be accompanied by the inversion of configuration of the attacked carbon atom. It is quite certain that the attack does not take place on carbon atom 2, because in such a case the reaction product would be the epimeric sugar derivative. Therefore, either carbon atom 1 or the central carbon atom of the orthoester group is attacked. In the first case, the reaction is as follows. 

The nucleophilic displacement reaction taking place at a saturated carbon atom is either a bimolecular substitution, Sv2 type, with complete Walden inversion, or a solvolytic reaction, characterized as a nucleophilic substitution of the first order, S l type, with predominant inversion. 

The general procedures previously outlined in this section for the formation of the carbon to azide bond have been widely employed in the steroid field, particularly as a stage in the stereospecific synthesis of aminosteroids. Bimolecular nucleophilic displacement reactions of sterols substituted with j -toluenesulphonyl, methanesulphonyl or halogeno groups etc. with azide ion proceeds with Walden Inversion and enables the stereospecific introduction of the azido group, which may then be reduced to an amino group. 

Citing the above three reactions as corroborating evidence, Kenyon and Phillips proposed that the inversion of configuration of an optically active R group accompanies S 2 nucleophilic displacement reactions. Does their data ... 

The reactions of McjSn with c -4-t-butylcyclohexyl bromide and with rra/w-4-t-butylcyclohexyl tosylate have been shown by H nmr spectroscopy to give the same product, and on the basis of independent evidence this product has been assigned the cir-configuration as shown in Scheme 7. Thus the reaction of the tosylate occurs by a nucleophilic displacement reaction with inversion of configuration at the carbon centre, and the bromide reaction apparently proceeds with retention (Koermer et al., 1972). 

Several authors have noted, although sometimes on a purely qualitative basis, that the rates of the reactions of a particular nucleophile with an alkyl or aryl halide vary inversely with the C—X bond strength (i.e. I > Br > Cl), as would be expected for a nucleophilic displacement reaction (Ochiai et al., 1969 Hart-Davis and Graham, 1970, 1971 Schrauzer and Deutsch, 1969 ... 

The binding of the nucleophile to the boron atom in structure 5 facilitates the internal migration and nucleophilic displacement with inversion to the point that side reactions such as P-elimination are not observed. Strongly basic nucleophiles work best in the conversion of 4 into 7, but the displacement process is assisted by the boron atom even if a fiilly covalent bond to boron is probably not involved [9j. 

Winstein and Lucas, 1939), who assume that an a-lactone is formed from the bromo acid by a nucleophilic displacement involving inversion a second inversion is associated with the hydrolysis of this lactone. Arguments in favor of the hypothesis that the opening of such a three-membered ring is associated with an inversion have been advanced by Hammett (1940). This mechanism can, of course, also be applied to the reactions under discussion the diazonium ion is transformed to an a-lactone, which then reacts with either a hydroxyl or bromide ion or a water molecule to form an a-hydroxy or an a-bromo acid. 

Ions are extensively used as reagents and as catalysts because they are highly reactive. In solution, ions have a strong interaction with the solvent and, as we discuss in Chapter 11, this behavior leads to essential modifications of the dynamics. Therefore, to study their intrinsic behavior we examine here ion-molecule reactions in the gas phase, continuing from the discussion in Section 3.2.6. Specifically, we consider nucleophilic displacement reactions of the type X + RY XR + Y . Such gas-phase Sn2 ion-molecule reactions proceed with reaction rate constants that vary from almost capture-controlled to so slow that they can barely be detected. Moreover, the rate constant exhibits an inverse temperature dependence, that is, the rate of nucleophilic displacement slows down with increasing temperature. This behavior is in marked contrast to the predictions of the Arrhenius equation. 

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