Electrophilic reactants

If the thiazole under consideration reacts in its neutral form, the ring nitrogen is expected to be reactive center. Exceptions could be expected for 2-araino-4-R thiazoies with bulky R groups and for electrophilic reactants able to generate a carbocation. 

Other Electrophilic Reactants. ReversibHity of the electrophilic reactions enables substituted dye derivatives to be obtained. Thus, the halogenation of cyanines, oxonoles, and merocyanines has been studied (3,65,66). Halogen atoms are mobHe in the polymethine chain, and the derivatives themselves can function as halogenation reagents. 

Enamines 1 are useful intermediates in organic synthesis. Their use for the synthesis of a-substituted aldehydes or ketones 3 by reaction with an electrophilic reactant—e.g. an alkyl halide 2, an acyl halide or an acceptor-substituted alkene—is named after Gilbert Stork. 

In general the Stork reaction gives moderate yields with simple alkyl halides better yields of alkylated product are obtained with more electrophilic reactants such like allylic, benzylic or propargylic halides or an a-halo ether, a-halo ester or a-halo ketone. An example is the reaction of 1-pyrrolidino-l-cyclohexene 6 with allyl bromide, followed by aqueous acidic workup, to yield 2-allylcyclohexanone ... 

Interestingly, the reactions were modestly slower in the presence of the Lewis acid. It is suggested that the catalyst inverts the HOMO-LUMO relationships, making the complexed nitrone the electrophilic reactant. In agreement with this interpretation, the reaction is favored by EWGs on the aromatic ring. 

Calculation of the appropriate local reactivity parameters (values for nucleophilic attack for the electrophilic reactant and vice versa)... 

Considerable effort has been devoted to finding Lewis acid or other catalysts that could induce high enantioselectivity in the Mukaiyama reaction. As with aldol addition reactions involving enolates, high diastereoselectivity and enantioselectivity requires involvement of a transition state with substantial facial selectivity with respect to the electrophilic reactant and a preferred orientation of the nucleophile. Scheme 2.4 shows some examples of enantioselective catalysts. 

Most C,H-acidic compounds can be condensed with aldehydes or ketones to yield alkenes. Some of these reactions have also been realized on insoluble supports, with either the C,H-acidic (nucleophilic) reactant or the electrophilic reactant linked to the support. Some illustrative examples are listed in Table 5.6. Polystyrene-bound malonic esters or amides, cyanoacetamides, nitroacetic ester [95], and 3-oxo esters undergo Knoevenagel condensation with aromatic or aliphatic aldehydes. Catalytic amounts of piperidine and heating are generally required, although reactive substrates can react at room temperature. 

Key variables for controlling these processes include solvent temperature concentration of the various reactants stirring rate type of PTC process (L/L or S/L) structures and nature of various protecting groups in the nucleophilic and electrophilic reactants stmcture of the catalyst and, finally, identity of counterions in the catalyst, alkyl halide, and base. 

The electrophilic character of n-perfluoroalkyl radicals was confirmed by a correlation of the rates of addition of the n-C8F17 radical to a series of para-substituted styrenes with Hammett o values, as shown in Fig. 3. The p value is negative (-0.53), as would be expected for an electrophilic reactant [115]. 

The effect of substituents on the rate constant for reaction of H with benzene was also examined. Correlation with Hammett s substituent constants was possible and showed that the hydrogen atom behaves as a slightly electrophilic reactant (Neta, 1972a, and references therein see also Brett and Gold, 1971, 1973 and photochemical studies by Pryor et al., 1973). 

A study35,36 concerning the ambidentity of the lithium salts of imines resulted in the discovery that the lithium is bonded to the nitrogen, e.g. compare 8 (equation 3). However, the evolution of the products on the carbon or nitrogen is influenced by the nature of the electrophile reactants like methyl iodide that ionize with difficulty will form a six-centered transition state 21 where the C-alkylation product will be evolved after elimination of lithium iodide. In the same way, the intermediate in aldol condensation is 22. 

Ambident anions are mesomeric, nucleophilic anions which have at least two reactive centers with a substantial fraction of the negative charge distributed over these cen-ters ) ). Such ambident anions are capable of forming two types of products in nucleophilic substitution reactions with electrophilic reactants . Examples of this kind of anion are the enolates of 1,3-dicarbonyl compounds, phenolate, cyanide, thiocyanide, and nitrite ions, the anions of nitro compounds, oximes, amides, the anions of heterocyclic aromatic compounds e.g. pyrrole, hydroxypyridines, hydroxypyrimidines) and others cf. Fig. 5-17. 

Cycloadditions. [2+1], [2 + 2], and [4 + 2] cycloadditions with electrophilic reactants such as carbenes (eq 5), tetracya-noethylene (eq 6), and a-keto-, Y-unsaturated nitriles (eq 7) lead to interesting products which are all enantiopure see, for instance, the 5-amino-6-hydroxy-2-keto acid (5). 

Noyori s acetalization procedure and its variants have been used for the preparation of chiral cyclic acetals. The rigid 1,3-dioxolanes formed play an important role as temporary chiral auxiliaries in stereoselective reactions and as electrophilic reactants. ... 

Detailed ICR analysis of the complex reaction pattern induced by the attack of the ions from biacetyl (acetyl, biacetyl, and triacetyl ions) on pyrrole has allowed the demonstration of single and double resonance effects on the abundance of the product ions (72JA6862 73IJM195). Interestingly, triacetyl cations have been found to be more reactive than biacetyl ions toward pyrrole (rate constants 11 versus 4.3 x 10 ° cm molecule sec ), whereas acetyl cations appear unreactive. Furthermore, the rate of the gas-phase reaction of biacetyl cations with pyrrole is only four times as fast as with benzene, in striking contrast with the enormous reactivity difference of the two aromatic substrates measured for a number of electrophilic reactants in solution. 

Metabolic products vary with the type of enzyme inductions. In fetal rat livers, several compounds, such as 1- or 2-hydroxy-, cis- and ra s-dihydroxy-, 11,12-dihydroxy-ll,12-dihydro-, and 1- and 2-keto-3-cholanthrene have been identified. Most frequently, it is the liver that produces a variety of electrophilic reactants that covalently bind to macromolecules. Metabolism or bioactivation may also be extramicrosomal or be carried out by fetoplacental tissue or gut bacteria. 

Miller, E. C., Miller, J. A. Studies on the mechanism of activation of aromatic amine and amide carcinogens to ultimate carcinogenic electrophilic reactants. Ann. N. Y. Acad. Sci. 163, 731 (1969). 

Once it was appreciated that the nitrogen mustards were acting as electrophilic reactants, alkylating essential cellular macromolecules, other types of chemical with similar properties were tested for their tumour inhibitory action. 

These reactions are often accompanied by dissociation of metal-oxygen bond (Aai process). For example, the element-oxygen bond (e.g., siloxane bond in silica) is cleaved readily by nucleophilic or electrophilic reactants... 

At higher temperatures species may appear at the conditions, the peroxide ion the ion radical 0. Both electrophilic reactants which... 

The formation of the transition state for reaction (7.3.23) is shown in fig. 7.6. The electrophilic reactant is the simple molecule methyl iodide, which has tetrahedral geometry with respect to the carbon atom. As the attacking chloride ion... 

Three minima are seen, symmetrically placed and corresponding to the three C—C bent bonds, and correspondingly in the space surrounding the molecule three channels of approach for electrophilic reactants are... 

From the electrostatic description it follows that in both molecules the most favored reaction channel for an electrophilic reactant X+ should lead to an intermediate of the type Va, completely different from that suggested for cyclopropane and in complete accord with chemical intuition. 

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