Neighboring Group Displacement Reactions

Similarly, certain rearranged products result from displacement reactions carried out with compounds containing amino nitrogen or tliio-sulfur atoms. Again these atoms appear to be involved in the actual intermediates. 

The Hydrolysis of cis and trans Cyclohexene Chlorohydrin. When trans cyclohexene chlorohydrin is treated with strong alkali, trans cyclohcxene glycol is obtained. Thus inversion does not appear to have occurred during the displacement. When the reaction is carried out with the cis isomer, cyclohexanone is formed.27 These facts can be explained if it is assumed that the first step in the reaction is the removal of a proton from the hydroxyl group (XXI to XXIII and XXII to XXIV), followed by the displacement of chloride ion by the alkoxide ion of the trans form (XXII1 to XXV) and by a hydride ion in the cis form (XXIV to XXVII). Displacement by alkoxide leads to cyclohexene oxide (XXV), and this intermediate can be further attacked by hydroxide ion to give the dl trans glycol (XXVI). Cyclohexanone is produced by the hydride displacement (XXIV to XXVII)  

With each isomer the course of reaction followed is the one which will permit a backside displacement of the chloride ion 

Since the action of dilute alkali on trans cyclohexene clilorohydrin constitutes a synthetic preparation for cyclohcxene oxide,28 there seems to be little doubt that the epoxide is an intermediate in the reaction of the trans chlorohydrin. There appears to be no evidence for the hydride ion displacement shown for the cis isomer. 

Rearrangements in the Displacement Reactions of 0-Hydroxy and 0-Haloamines or Sulfides. When displacement reactions are carried out with 0-hydroxy and 0-haloamines or sulfides, the product formed often is found to have the nitrogen or sulfur atom attached to the carbon atom where substitution would have been expected. The new substituent becomes affixed to the carbon atom which originally held the nitrogen or sulfur atom. Thus when the glycol XXVIII was treated with hydrochloric acid, the dichloride XXIX was obtained.29 It is 

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The last phases of B. R. Baker s work that was completely devoted to carbohydrate chemistry were carried out between 1963 and 1966, when he was in residence at the State University of New York at Buffalo. He studied Sn2 displacements in comparison with neighboring-group displacements in the l,2 5,6-di-0-isopropylidene-n-mannitol and related systems, and showed that the competition between the two types of replacement reaction depends on the nucleophilic nature of the substituent group and the nature of the neighboring group and he used... 

The dependence of the rate of an intramolecular nucleophilic displacement on the size of the ring that is being formed is determined by the interplay of at least three quantities (1) the entropy loss on formation of the transition state, (2) the increase in strain energy on formation of the transition state, and (3) the electronic effects of the neighboring group and reaction group on one another. 

The hydrolysis of 2,2 -bischloroethyl sulfide (mustard gas) was one of the first neighboring-group-accelerated reactions to get widespread attention. Initially the hydrolysis of this compound is purely first order in the sulfide, and the rate is unaffected by added alkali or other nucleophiles the increasing amount of chloride ion, however, slows the rate with time. Since formation of the primary carbocation is not expected, these data suggest an anchimerically assisted solvolysis [Eq. (1)], leading to the formation of the intermediate sulfonium ion (1), which may react with water, chloride ion, or any other nucleophile present. A second anchimerically assisted process that leads to displacement of the second chloro group can occur. 

FIGURE 21.13 Sulfiir can act as a neighboring group, displacing chloride in an intramolecular Sn2 reaction. An episulfonium ion is formed and can be opened in a second, intermolecular Sn2 reaction to give the product. 

This result is attributed to participation by the neighboring methoxy group at position 1 (formula 18) in the phosphorus pentachloride displacement reaction. A cyclic methoxonium ion (22) is postulated as the intermediate. The overall result is methoxyl migration from 1 to 6, with inversion of configuration at both positions (27). 

Imidazole-l-sulfonate Displacements at the C-3 and C-4 Positions of Sngar Derivatives. Displacement reactions of tosylates at the C-3 position of a-D-glucopyrano-side derivatives proceed with difficulty because of a nonbonded 1,3-diaxial interaction between the aglycone and the approaching nucleophile [32], as well as complications arising from neighboring group participation [90],... 

The Barton-McCombie deoxygenation reaction was invented for use in the manipulation of aminoglycoside antibiotics. It has become a popular method because of the mild conditions employed. Radical reactions have advantages over ionic reactions for carbohydrate chemistry. In this context, there is little neighboring group interference in cationic reactions and little elimination compared with normal nucleophilic displacement reactions. 

Kinetic isotope effect for lysozyme. A secondary kinetic isotope effect is expected because a molecule with H in the number 1 position can be converted to the corresponding oxocarbenium ion somewhat more easily than the molecule with 2H in the same position (Eq. 12-13). For example, in the nonenzymatic acid-catalyzed hydrolysis of a methyl- glucoside, a reaction also believed to proceed through a carbocation intermediate,41 75 the ratio h / h, is 1.14 for the a anorner and 1.09 for the (3 anorner.53 In the base-catalyzed hydrolysis of the same compound, which is believed to occur by a double-displacement reaction involving participation of the neighboring OH group on C-2, the ratio /c1h / /c2h is 1.03. The corresponding ratio measured... 

NADPH/ NADP+ ratio 776 Naphthalene, resonance energy 299 Nathans, Daniel 84 Natural killer cells 185 Near attack conformation 485 Near-field scanning microscope 130 Neighboring group assistance in displacement reactions 601, 602 Nekoflavin 783 Nematocyst 427 Nematodes 24, 25 Neocarzinostatin 218,224s Neopterin 803... 

The extensive work of Winstein and his coworkers21 on the general concept of the influence of neighboring groups and atoms on the reactivity toward displacement reactions has added much information indicating the validity of cyclic reaction intermediates. 

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