Methyl chloride nucleophilic substitution

Imid azolin-2-ones polymers, 1, 296 synthesis, 5, 466, 491 Imidazolium cations, 2-fluoro-nucleophilic substitution, 5, 413 Imidazolium chloride, 4-amino-l-methyl-2,3-diphenyl-... 

For carbon-carbon bond-formation purposes, S 2 nucleophilic substitutions are frequently used. Simple S 2 nucleophilic substitution reactions are generally slower in aqueous conditions than in aprotic organic solvents. This has been attributed to the solvation of nucleophiles in water. As previously mentioned in Section 5.2, Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions (Scheme 6.1). In alkylations of phenoxide ions by benzylic chlorides, S/y2 substitutions can occur both at the phenoxide oxygen and at the ortho and para positions of the ring. In fact, carbon alkylation occurs in water but not in nonpolar organic solvents and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para). The effects of phenol substituents and of cosolvents on the rates of the competing alkylation processes... 

Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions of phenoxide ions by benzylic chlorides carbon alkylation occurs in water but not in nonpolar organic solvents, and it is observed only when the phenoxide has at least one methyl substituent (ortho, meta, or para). This has been discussed in Chapter 6 (Section 6.4.2). 

Thioetherification of PECH is feasibly performed in DA-solvents as already described in the patent (20J. For example, the highest substitution was obtained by the reaction of P(ECH-EO)(1 1 copolymer of epichloro-hydrin and ethylene oxide) and equimolar thiophenoxide in HMPA at 100°C for 10 h as DS 83% for sodium and 93% for potassium salts. The DS in our nucleophilic substitution was estimated by the elemental analysis as well as the titration of liberated chloride ion with mercuric nitrate (21). In the latter method, reacted medium was pretreated with hydrogen peroxide when the reductive nucleophiles which can react with mercuric ion were used. As described before for PVC, thiolation was also achieved conveniently with iso-thiuronium salt followed by alkaline hydrolysis without the direct use of ill-smelling thiolate. The thiolated PECH obtained are rubbery solids, soluble in toluene, methylene chloride, ethyl methyl ketone and DMF and insoluble in water, acetone, dioxane and methanol. 

It used to be postulated that the magnitude of the alpha-carbon KIE in an Sn2 reaction is an indication of the transition state symmetry. The expectation was that this KIE reaches maximal value for a symmetric transition state and drops back to unity for extremely early or late transition states. That expected behavior is marked by the solid line in Fig. 10.10. However, recent calculations of the nucleophilic substitution of chloride from methyl chloride by a broad variety of nucleophiles... 

The cathodic coupling of prenyl chloride with diethyl fumarate and methyl crotonate proceeds with different regios-electivities as shown in Fig. 17 [94]. Also in this case, the change in the regioselectivity appears to be due to the reduction of the diethyl fumarate to a radical anion that undergoes a nucleophilic substitution at the prenyl chloride, and in the other case there is a 2e reduction of the prenyl... 

Nucleophilic substitution on methyl / -nitrobenzenesulfonate in CH2CI2 has been studied with a series of chloride salts with different structures and solvations BU4NCI, PPNCl [bis(triphenylphosphoranylidene)ammonium chloride], KCl complexed by 18-crown-6 or Kryptofix 2,2,2, and for comparison PPNBr. ° Rate constants and activation parameters are in accordance with an S 2 mechanism. The results were treated by the Acree equation. There are two reaction paths the first, involving the chloride ion, has the same rate for all the salts, whereas the second slower path, involving the ion pair, has a rate related to the dissociation constant of the salt. 

Rearrangements may also be observed in these carbocations if they have the appropriate stmctnral featnres. It does not matter how the carbocation is prodnced, subsequent transformations will be the same as we have seen where rearrangements are competing reactions in nucleophilic substitution. Thus, electrophilic addition of HCl to 3,3-dimethylbut-l-ene proceeds via protonation of the alkene, and leads to the preferred secondary rather than primary carbocation (see Section 8.1.1). However, this carbocation may then undergo a methyl migration to produce the even more favonrable tertiary carbocation. Finally, the two carbocations are quenched by reaction with chloride ions. The prodnct mixture is found to contain predominantly the chloride from the rearranged carbocation. 

Consider the reversible transformation of the soil fumigant methyl bromide (CH3Br) to methyl chloride (CH3C1) in aqueous solution (a nucleophilic substitution reaction, see Chapter 13) ... 

Depending on the relative nucleophilicities, [Nu]50% ranges from micromolar to molar concentrations (Table 13.5). Although these values represent only order-of-magnitude estimates, they allow some important conclusions. First, in uncontaminated freshwa-ters (where bicarbonate typically occurs at about 10"3 M, chloride and sulfate occur at about 10 4 M, and hydroxide is micromolar or less, Stumm and Morgan, 1996), the concentrations of nucleophiles are usually too small to compete successfully with water in SN2 reactions involving aliphatic halides. Hence the major reaction will be the displacement of the halide by water molecules. In salty or contaminated waters, however, nucleophilic substitution reactions other than hydrolysis may occur Zafiriou (1975), for example, has demonstrated that in seawater ([CL] 0.5 M) an important sink for methyl iodide is transformation to methyl chloride ... 

The above reactions in this section have been examples of addition alone or addition followed by elimination. Ligand reactions involving nucleophilic substitution are also known and these are of the dealkylation type. Lewis acids such as aluminum chloride or tin(IV) chloride have been used for many years in the selective demethylation of aromatic methyl ethers, where chelation is involved (Scheme 27). Similar cleavage of thioethers, specially using mercury(II) salts, is commonly used to remove thioacetal functions masking ketones (equation 27).104 In some cases, reactions of metal ions with thioether ligands result in isolation of complexes of the dealkylated organic moiety (equations 28 and 29).105-107... 

The nucleophilic properties of pyridine nitrogen have been assessed in studies on pyridine-catalyzed Schotten-Baumann reactions133 and aromatic sulfonyl chloride hydrolyses,134 from which highly accurate Bronsted and Hammett treatments arise. There is some doubt as to the mechanism of this reaction.45 Equations (13) and (14) accurately express the reactivity of 3- and 4-substituted pyridines toward ethyl iodide (using rate for equilibrium constants),133 while rates of N-methylation of 2-substituted pyridines have been used to estimate both steric and electronic effects.136... 

Reactions of 5f/-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-one 71, prepared by reaction of 1,2-diaminobenz-imidazole 72 with acetoacetic ester 73, with different reagents was described, in the search of new heterocycles with biological activity <2002CHE598>. When lactam 71 was treated with aromatic aldehydes in boiling 1-BuOH with addition of piperidine 74, 577-3-arylidene-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-ones 75a-c were obtained (Scheme 7). Coupling lactam 71 with phenyldiazonium chloride 76 in dioxane afforded the 3-phenylazo-substituted tricycle 77. When 71 was treated with phosphorus pentasulfide 78 in boiling dioxane or pyridine, its thio analog 79 was obtained. The reaction proceeded most efficiently when lactam 71 was refluxed with twofold excess of 78 in dry dioxane. These thiones 79 react with ammonia and amines by nucleophilic substitution. When 79 was refluxed with ammonia, benzylamine, piperidine, or morpholine, the 4-amino-substituted tricycles 80a-d were obtained. All the described compounds were identified by NMR, mass spectrometry, and IR spectroscopy. 

Two other nucleophilic substitution reactions of pyridine iV-oxides deserve mention and further study to determine the effects of substituents. Pyridine N-oxide, benzoyl chloride, and the piperidine enamine of cyclohexanone give a good yield of 2-(2 -pyridyl)cyclo-hexanone (155) (63%).360 When W-methoxy-4-picolinium methyl... 

Benzotrichloride Method. The central carbon atom of the dye is supplied by the trichloromethyl group fromy>-chlorobenzotrichloride. Both symmetrical and unsymmetrical triphenylmethane dyes suitable for acrylic fibers are prepared by this method. 4-Chlorobenzotrichloride is condensed with excess chlorobenzene in the presence of a Lewis acid such as aluminium chloride to produce the intermediate aluminium chloride complex of 4,4, 4"-trichlorotriphenylmethyl chloride (18). Stepwise nucleophilic substitution of the chlorine atoms of this intermediate is achieved by successive reactions with different a.rylamines to give both symmetrical (51) and unsymmetrical dyes (52), eg, N-(2-chlorophenyl)-4-[(4-chlorophenyl) [4-[(3-methylphenyl)imino]-2,5-cyclohexadien-l-yhdene]methyl]benzenaminemonohydrochloride [85356-86-1] (19) from / -toluidine and a-chloroaniline. 

Koskikallio (1972) has found that the selectivity of certain methyl derivatives which undergo nucleophilic substitution remains essentially constant despite large differences in reactivity. The data are shown in Table 9. The methyl halides, in contrast, show selectivity differences, but in the opposite direction to that predicted by the reactivity-selectivity principle. Methyl iodide is more selective than methyl bromide which is in turn more selective than methyl chloride. The data are presented in Table 10. Koskikallio interpreted this data... 

Carbonyl groups increase the reactivity of adjacent leaving groups towards nucleophilic substitution by several orders of magnitude. This was an effect that we noted in Chapter 17, where we showed that the ketone below reacts by the S>j2 mechanism 5000 times as fast as methyl chloride itself. 

One important point regarding relative reactivities of Af-unsubstituted and Af-substituted 2-chloroimidazoles with powerful nucleophiles such as alkoxide is that in the former there is competition between proton abstraction from N-1 (which severely hampers any nucleophilic attack at C-2) and the nucleophilic substitution at the 2-position. Thus, chloride is not displaced from 2-chlorobenzimidazole by alkoxide ions, whereas 2-chloro-l-methyl-benzimidazole reacts readily. That steric effects can also be important is evidenced by the lack of reactivity of 2-chloro-l-methylbenzimidazole with t-butoxide, and similar resistance to nucleophilic attack of 2-chloro-l-isopropylbenzimidazole. Alkoxide readily displaces chloride from 2-chloro-1 -isopropenylbenzimidazole, and the N- substituent may be removed subsequently by oxidative cleavage (74CRV279). 

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