Substitution Menschutkin reaction

Reactions that take place through dipolar transition states Menschutkin reaction (10-44), electrophilic aromatic substitution. 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

The Menschutkin reaction of benzyl tosylates [21]-OTs with dimethyl-anilines or pyridines in acetonitrile generally proceed by a second-order bimolecular Sn2 mechanism for most ring-substituted compounds the plot of obs vs. [Nu] passes through the origin within experimental uncertainty (Yoh et al., 1989). However, for the reactions of strong ED derivatives under the same conditions, it was found that there was a significant intercept (i.e. a first-order component) in the kobs vs. [Nu] plots represented by (39) the intercept is a constant of the benzyl substrate independent of the amine nucleophiles, indicating a concurrent reaction zeroth-order in amine (Kim et al., 1995, 1998). 

Fig. 37 More O Ferrall-Jencks diagram for the Menschutkin reactions of 1-phenylethy] and benzyl chlorides with pyridine. The structures of transition states were optimized by ab initio MO calculation (RHF/b-Sf G ). O, substituted 1-phenylethyl chlorides with pyridine , benzyl chlorides with pyrindine , with 4-nitropyridine O, methyl and A, ethyl chlorides with pyridine (Fujio et al, unpublished).

Contrary to reactions going through isopolar transition states, reactions of types 3 to 8 in Table 5-25, which involve formation, dispersal or destruction of charge, should exhibit large solvent effects on their activation volumes. This is shown in Table 5-27 for the Sn2 substitution reaction between triethylamine and iodoethane [441], an example of the well-known Menschutkin reaction, the pressure dependence of which has been investigated thoroughly [439-445, 755],... 

Aniline nucleophiles were used in the early days in the Menschutkin reaction with alkyl halides in a variety of solvents1-6 and have made important contributions in the development of the Hammett equation7. However, due to the narrow range of basicity (pX a = 1.02-6.08 for 4-NO2-4-NH2 substituted anilines8, and 0.67-5.89 for 4-N02-4-... 

Another example of nucleophilic attack of anilines at an oxygen atom has been reported by Buxton and coworkers134. The oxidation of 4-substituted /V,/V-dimethylanilines by dimethyldioxirane, 13, in acetone showed a similar qualitative trend as those for the reactions at the Mel and benzoyl peroxide reactions with a reactivity decrease in the order X = MeO > H > Cl N02. These trends suggest that the oxidation of DMAs by 13 is electrophilic. The px value of —0.89 shows similarity to the values in the reactions of DMAs with Mel (Menschutkin reaction) which has a px value of —3.30 at 35 °C in 90% aqueous acetone. While in the latter reactions the TS is thought to have developed almost a full positive charge, the reactions with 13 have much less charge development partially due to steric crowding in the TS (Scheme 17). 

E.M. Arnett and R. Reich, Electronic Effects in the Menschutkin Reaction. A Complete Kinetic and Thermodynamic Dissection of Alkyl Transfer to 3- and 4-Substituted Pyridines, J. Am. Chem. Soc., 1980,102, 5892. 

Harris et al. reported (11) a large variation of the deuterium KIE in the Menschutkin reaction of methyl iodide with substituted pyridines (equation 3 X and Y = CH3, H, and Cl). Because this large variation seems to be good evidence for a change of TS in this series of reactions, the carbon KIE was measured. Reactions were carried out under the same conditions as reported... 

Pyridine-substituted nicotines, nornicotines, and anabasines are available from a-cyano-amines by a new synthesis. The syntheses of ( )-[l - N]nornicotine and ( )-[l - N]nicotine have been described, from cyclopropyl 3-pyridyl ketone and [ N]formamide. 4-Methylnicotine has been prepared it shows no nicotine-like pharmacological activity. " An investigation into the stereochemical factors involved in the behaviour of nicotine and related compounds in the Menschutkin reaction has been conducted.A bridged nicotine , 1,2,3,5,6,10b-hexahydropyrido[2,3-g]indolizine (44), has been synthesized by carboxylation of the dilithium derivative of 2-methylnornicotine followed by cyclisation and reduction with borane in tetrahydrofuran. Several 5-halogeno-nicotines have been prepared and their pK values and biological activities measured. ... 

Nucleophilic aliphatic substitution, as defined by (1), and typified in organic chemistry by the Finkelstein and Menschutkin reactions, can extend into inorganic chemistry with the inclusion of metal complexes which are sufficiently nucleophilic. The aim of this review is to collect the somewhat... 

As noted earlier, the replacement of halogen by an amino group (a substitution reaction at carbon and at nitrogen [ ]) is generally not useful for the preparation of primary (RNH2) or secondary (R2NH) amines since the alkylamines are stronger bases than ammonia. However, the substitution reaction is useful for tertiary (R3N) amines, for example, the A-methylation of pyridine with methyl iodide (Equation 10.48) and the formation of other quaternary ammonium salts (cf. the Menschutkin reaction. Table 7.7, item h). 

Three examples of Sn2 (substitution, nucleophilic, bimolecular) reactions are shown in Scheme 11.5. These are simple reactions from a mechanistic standpoint. They are concerted, and there is very little that can go wrong when considering the proper electron-pushing notation. These reactions fit our paradigm for predicting reactivity, because they are combinations of nucleophiles and electrophiles, whose reactivity can be predicted solely based upon electrostatic considerations. The specific reaction shown in Scheme 11.5 B is an example of the Menschutkin reaction, defined as the reaction between an amine nucleophile and an alkyl halide. Scheme 11.5 C shows the second step of the enolate alkylation reaction we described in Section 11.3. 

K. Okamoto, S. Fukui, I. Nitta, and H. Shingu, Bull. Chem. Soc. Jpn., 40, 2354 (1967). Kinetic Studies of Bimolecular Nucleophilic Substitution. VIll. The Effect of Hydroxylic Solvents on the Nucleophilicity of Aliphatic Amines in the Menschutkin Reaction. 

A-liphatic nucleophilic substitution played a central role in the recent debate on variable transition states (TS) (1-20). In previous papers (1-4), we successfully interpreted the variation in the TS structure of the Menschutkin-type reaction of benzyl benzenesulfonates with N,N-dimethylanilines (equation 1), by the extensive use of carbon-14 and tritium isotope effects. 

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