Displacement reactions demonstration

Nucleophilic Displacement Reactions. The presence of activating groups, eg, o,p mX.1.0 groups, makes aromatic fluorine reactive in nucleophilic displacement reactions. This has been demonstrated by deterrnination of the relative fluorine—chlorine displacement ratios from the reaction of halonitroben2enes with sodium methoxide in methanol (137) F is displaced 200—300 times more readily than Cl. 

Experiments ( P nmr) using 0.8 and 2 equivalents of octyhnagnesium chloride with ethyl ben2enephosphinate indicate that the nucleophilic displacement occurs first, foHowed by proton abstraction (80). Interestingly, the order of the two steps is reversed when methyhnagnesium chloride is used (81). This reaction demonstrates the difference ia reactivity between the octyl and the methyl Grignard reagents. 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

As a demonstration of the complete synthesis of a pharmaceutical in an ionic liquid, Pravadoline was selected, as the synthesis combines a Friedel-Crafts reaction and a nucleophilic displacement reaction (Scheme 5.1-24) [53]. The allcylation of 2-methylindole with l-(N-morpholino)-2-chloroethane occurs readily in [BMIM][PF6] and [BMMIM][PF6] (BMMIM = l-butyl-2,3-dimethylimida2olium), in 95-99 % yields, with potassium hydroxide as the base. The Friedel-Crafts acylation step in [BMIM][PF6] at 150 °C occurs in 95 % yield and requires no catalyst. 

Recently, Johnson and Jonsson (185) as well as Jones and Cram (166) demonstrated that the replacement of chlorine in the optically active sulfonimidoyl chlorides 163 and 167 by phenoxy or dimethyl-amino groups occurs with inversion of configuration. The syntheses of both chlorides and displacement reactions are shown in Schemes 12 and 13 (see page 382). 

It is important to note that SNAr displacement reactions of heteroatom functional groups other than halides have been demonstrated on purine substrates, including mesitylenesulfonates <20000L927>, sulfones (see Section 10.11.7.5), nitro substituents <2006S2993>, and T-azoles (see Section 10.11.7.3.2). Halopurines have been reduced using sodium naphthalenide <1997T6295>. 

To demonstrate the problems associated with ex-chiral-pool syntheses, some typical examples are given in this section. Three start with n-glucose, which is by far the most popular substrate in ex-chiral-pool synthesis, and illustrate the key transformations, in the first example, D-glu-cose is transformed into the mannosidase inhibitor iV-acetyl-4-deoxymannosamine by 4-deoxygenation and a SN2 displacement reaction of nitrogen introducing an amino function in place of a 2-hydroxy function 5. 

The scope of the copper promoted nucleophilic displacement reactions on heterocyclic systems is not limited to nitrogen, oxygen and phosphorous nucleophiles. Buchwald and co-workers demonstrated that the same catalyst system that is efficient in carbon-phosphorous bond formation is also the... 

Alternatively, the remaining sulfate ester of 70 may serve as a leaving group for a second nucleophilic displacement reaction. When this displacement is by an intramolecular nucleophile, a new ring is formed, as was first shown in the synthesis of a cyclopropane with malonate as the nucleophile [68] and of aziridines with amines as the nucleophiles [76]. The concept is further illustrated in the double displacement on (/J,/ )-stilbenediol cyclic sulfate (72) by benzamidine (73) to produce the chiral imidazoline 74 [79]. Conversion of the imidazoline (74) to (.V,.S )-stilbenediaminc 75 demonstrates an alternative route to optically active 1,2-diamines. Acylation of 75 with chloroacetyl chloride forms a bisamide, which, after reduction with diborane, is cyclized to the enantiomerically pure trans-2,3-diphenyl- 1,4-diazabicy-clo[2.2.2]octane (76) [81],... 

It was however demonstrated by using O-labeling that the formation of B-lactam 152 under these strong acid conditions occurs by an SNj type displacement reaction on the methoxy group by chloride ion (cf. 154), and the formation of methyl chloride was observed experimentally. 

Demonstrate their displacement reactions. R Add chlorine water to potassium bromide solution. Add chlorine water to potassium iodide solution. Add bromine water to potassium iodide solution. 

To facilitate the nitro group displacement reaction, the thioethers 7, obtained by treatment of difluoride 6 with thiols, were oxidized with 3-chloroperbenzoic acid to afford the corresponding sulfones 8 (Fig. 4). The resulting sulfones 8 showed the expected high reactivity toward nucleophiles, as demonstrated by the efficient displacement of both the second fluoride and the nitro group with two different aliphatic amines to yield the highly substituted benzamides 10. 

After free existence of l-azetin-4-one had been demonstrated, it seems that the mechanism of the so-called nucleophilic substitution reactions of 4-substituted 2-azetidinone follows an elimination-addition pathway. The intermediacy of (1) in displacement reactions is fully consistent with the stereochemistry of the reaction (83CJC1899 91TL2265). 

Tucci and Holm [163] have demonstrated an alternative reaction scheme, starting from the complex [NIi(bpy)(CH3)2(SR")2], where bpy is 2,2 -bipyridyl and R" is aromatic. In this case, the thiol displaced one methyl group from the nickel as methane, in a reaction reminiscent of methyl-CoM reductase, and coordinated to the nickel. Further addition of CO liberated CH3COSR" in high yield. This reaction demonstrates the feasibility of a reaction in which both the thiol and acetyl groups coordinate the nickel. 

The marked activation of the iV-oxide function on the chlorine atom of 2-chloropyrazine 4-oxide and 2-ehloro-3,6-dimethylpyrazine 4-oxide is also demonstrated by the milder conditions under which these compounds react with ammonia and amines compared with chloro-pyrazine and 2-chloro-3,6-dimethyl pyrazine, respectively. Although 2-chloropyrazine 4-oxide undergoes the expected displacement reaction with ammonia on heating at 115°-120° for 2.5 hours, reaction at 140° for 16 hours gives 2,3-diaminopyrazine, possibly as a result of an addition-elimination reaction on the initially formed 2-amino-pyrazine 4-oxide (Scheme 47).417... 

A typical example of such reactions is the exothermic Sn2 nucleophilic displacement reaction Cl -I- CH3—Br Cl—CH3 - - Br . Table 5-2 provides a comparison of Arrhenius activation energies and specific rate constants for this Finkelstein reaction in both the gas phase and solution. The new techniques described above cf. Sections 4.2.2 and 5.1) have made it possible to determine the rate constant of this ion-molecule reaction in the absence of any solvent molecules in the gas phase. The result is surprising on going from a protic solvent to a non-HBD solvent and then further to the gas phase, the ratio of the rate constants is approximately 1 10 10 The activation energy of this Sn2 reaction in water is about ten times larger than in the gas phase. The suppression of the Sn2 rate constant in aqueous solution by up to 15 orders of magnitude demonstrates the vital role of the solvent. 

It has been demonstrated that only a small number of solvent molecules are needed to bridge most of the gap between the enthalpy diagram for nucleophilic displacement reactions in the gas phase and that in solution [475, 477, 485-488]. 

The results for reaetion no. 8 in Table 5-15 indieate that nueleophilie reaetivities of anions obtained in the gas phase are essentially in the same order as in molten salts and in dipolar non-HBD solvents [285, 290]. This again suggests that speeifie solvation of the anions is responsible for the reversed order obtained in protie solvents relative to dipolar non-HBD solvents. Whereas the relative nueleophilieities in aeetonitrile are similar to those found in the gas phase [282, 285, 290], the absolute gas-phase rates are some orders of magnitude greater than those in aeetonitrile. The speeifie rates of displacement reactions of anions with halomethanes exceed those in solution by factors of up to >10 [285, 290]. These large differences in absolute rates demonstrate the moderating influence of the solvent on all the reactivities [282]. See also Chapter 5.2. 

It is interesting to note that the base displaced need not be a simple one, that is, dihydrogen is exclusively displaced from [HFe3(CO)9(/u-H)2BH] (equation 10). Indeed, a comparison of equations (10) and (11) demonstrates that cluster composition is important in determining the outcome of a Lewis base displacement reaction on a transition metal-main group element cluster. This implies that control of electronic structure via cluster element composition is a viable means of controlling reactivity. 

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