Meisenheimer adduct

The infrared spectra of adducts such as (5) formed between alkyl picrates and alkoxides show changes relative to the parent compounds that are consistent with a fully covalent structure. A series of strong bands between 1225 and 1040cm is typical of ketals [118, 119]. Many sigma adducts are intensely colored, and attempts have been made to correlate UV-visible spectra with structural features [120]. However, these spectra do not generally provide such precise information as do NMR studies. Nevertheless, the absorption intensity usually obeys the Beer-Lambert law, so that absorption is directly proportional to concentration, and this is very useful in the determination of concentrations in kinetic and equilibrium studies. 

The H NMR spectra of sigma adducts were first reported in the 1960s [121, 122], and since then, the technique has proved invaluable in structural determinations. The method is 

The UV-visible spectra of these adducts typically show two absorption maxima, and data are included in Table 6.3. At higher methoxide concentrations, conversion to adducts with 2Nu 1 TNB stoichiometry results in a broad adsorption with maximum circa 500 nm [84]. 

A strength of the NMR method is that with ambident nucleophiles changes with time in the adducts present can be readUy detected. Thus, with acetophenone anions [131], the oxygen-bonded 

TABLE 6.3 Representative Data for Adducts with Structure (35) from Trhiitrobaizaie 

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FEEDBACK INHIBITION ADDITIVITY PRINCIPLE ADDUCT COMPLEX LEWIS ADDUCT MEISENHEIMER ADDUCT Adenine,... 

LEWIS ACID LEWIS ACIDITY LEWIS BASE LEWIS BASICITY MEISENHEIMER ADDUCT LEWIS BASE LEWIS ACID LEWIS BASICITY... 

MEISENHEIMER ADDUCT LEWIS BASICITY DONOR NUMBER HARD BASES LEWIS BASE NUCLEOPHILICITY SOFT BASES L HOPITAL S RULE L Hospital s rule L HOPITAL S RULE... 

MEISENHEIMER ADDUCT TWO-PROTONIC STATE ELECTROPHILES Melilotate,... 

According to a recent IUPAC resolution,18 we shall use the terms Meisenheimer adduct, or a-adduct, rather than the widely used but less precise terms Meisenheimer complex or ff-complex. 

Because the Meisenheimer adducts are usually characterized by intense UV-visible absorption bands, the equilibrium constants for their formation (K) can be determined spectrophotometrically by standard methods, whether complete conversion to the adduct can be attained39 or not,60 depending on the equilibrium constant value (K 5 10). 

Although the information concerning the influence of structural changes in azine substrates on the formation of Meisenheimer adducts is still rather limited, there are enough quantitative data for the reactions with MeO to permit some general features to be fairly well established and to illustrate the importance of such data as a valuable complement for a better understanding of the dynamics of adduct formation in homocyclic series. The aim of this section is to utilize such data, which have been presented in the preceding sections, in order to interpret them from the point of view of structural effects. 

The increase in stability with the DMSO content is a general feature for Meisenheimer adduct formation and is observed to similar extents for pyridine as well as benzene adducts. It is mainly caused by the enhanced nucleophilicity of the RO ion, resulting from a decreased specific solvation of the charged reagent as the concentration of the protic solvent is decreased and dispersion interactions between the large, polarizable adduct and the dipolar aprotic solvent.36,83... 

Even if the addition of DMSO to protic solvents has a dramatic effect on the rate and equilibrium constants for adduct formation, to a first approximation it does not affect the relative stability of adducts formed from the same substrate. As already observed in the chemistry of Meisenheimer adducts in the benzene series, the ratios Kk/Kt, kf/kj, and k /k] are practically independent of the composition of the medium.46 Under such circumstances it is possible to obtain approximate kinetic or thermodynamic data for a given adduct in a particular medium whenever kinetic and... 

A well understood case is that of quinoline reaction at position 2 is kinetically favored as compared with reaction at position 4, but the adduct from the latter is thermodynamically more stable. This situation, where the site of attack leading to the more stable adduct is the y position, is analogous with those regarding the formation of Meisenheimer adducts from benzene and pyridine derivatives and RCT nucleophiles. Presumably, with quinoline kinetic control favors the position that is more strongly influenced by the inductive effect of the heteroatom. The fact that position 2 of quinoline is the most reactive toward nucleophilic reagents is probably related to the lower 71-electron density at that position.123 However, the predominance of the C-4 adduct at equilibrium can be better justified by the atom localization energies for nucleophilic attachment at the different positions of quinoline. Moreover, both 7t-electron densities and atom localization energies indicate position 1 of isoquinoline to be the most favored one for nucleophilic addition. 

A number of Meisenheimer adducts from the reaction of selenophene derivatives 141, which are analogs of series 121, with methoxide ion have been investigated and characterized.I<9- 81 Their formation is generally even easier than that of the related sulfur compounds. 

Although the tendency of benzofuroxan derivatives to interact with electron donors has been known since Drost s early report197 199 firm experimental evidence on the formation of Meisenheimer adducts was not reported until the 60s for the reaction of 4,6-dinitrobenzofuroxan with RO nucleophiles200 202 (Eq. 25). Information on benzofurazans became available even later with an NMR study by Terrier, Simonnin, and their co-workers.203... 

There is evidence for the formation of Meisenheimer adducts in aqueous solution with nucleophiles other than HzO or OH. The formation of transient adducts has been assumed in the interaction of 160 with the basic components of buffer systems such as carbonate and bicarbonate ions222 and phenoxide ions.224... 

The cyclization of 7-(2-hydroxyethoxy)-4-nitrobenzofurazan and 7-(2-hydroxyethoxy)-4-nitrobenzofuroxan to give the spiro Meisenheimer adducts 169 and 170, respectively, was investigated by Terrier et al.212 in aqueous solution by a detailed equilibrium and rate analysis similar to the one described for the reaction of 160. 

Adduct 172 and its furoxan analog 189 are rated as the most stable Meisenheimer adducts known so far and exceed the stability of adduct 143... 

In the course of investigations using 4-chloro-7-nitrobenzofurazan as a reactivity probe for identifying the active sites of a number of enzymes such as papain, ficin, and bromelain, the intermediacy of Meisenheimer adducts derived from direct attack of thiolate groups located in the protein has been assumed on the basis of the spectral changes accompanying the process of replacement of the chloro group.232,233... 

If the thiophene ring bears one or more N02 groups, it becomes susceptible to nucleophilic attack by alkoxide ion an anionic cr-complex is thus produced which can be isolated in some cases. This is called a Meisenheimer adduct, and corresponds to the first step in many nucleophilic substitution reactions on activated thiophene substrates. The similarity between these adducts and heterocyclic pseudobases has been pointed out (79AHC(25)l). Kinetic data lead to similar rate equations for both processes both are characterized by negative entropies of activation of similar magnitude. 

NMR evidence has been provided for the formation of Meisenheimer adducts in DMSO solution from several mononitrothiophenes (70JHC1441, 74JHC97, 75JHC327). Interesting examples of the formation of spiro adducts have also been recorded (Scheme 137) (75JHC1083) one of these appears to be the first Meisenheimer complex observed at position 3 of thiophene. 

The source of cyanide ions is the Meisenheimer adduct formation between trinitrobenzene and cyanide ions in equilibrium 25. The constant of this equilibrium 25 is well known if the equilibrium concentration of free cyanide ions is negligible, the concentration of the strong red 137 provides a proof of equilibrium 24. Also, in the case of equilibrium 24, DMSO enhances the reactivity of the anionic nucleophile compared with protic solvents. 

Reaction with nucleophiles, in particular potassium hydroxide and methoxide, forms Meisenheimer adducts similar to those of dinitrobenzofurazan IV-oxide, in both structure and explosivity, but even more readily. 

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