Electrophilic attack

Mechanism of Attack of Main Group Eiectrophiies on Aikyi Complexes Possessing d-Eiectrons 

Electrophilic attack. Reaction of cyclobutadienetricarbonyliron with electrophilic reagents leads to the substitution of hydrogen in the ring. This is an analogous reaction to hydrogen substitution in cyclopentadienyl complexes. Reactivities of Fe(C4H4)(CO)3 and Fecp2 are similar. 

Acetylation and benzoylation give acetyl and benzoyl derivatives, respectively [equation (8.76)]. Mercuration reactions occur unusually easily, leading to the formation of an equilibrium mixture of all possible complexes [equation (8.77)]. The reaction 

The electrophilic attack may occur on the metal center, which is the usual case since the metals have usually the highest electron density and can therefore be protonated. In most cases the resulting hydrido ligand will occupy a bridging position  

In some cases the electrophilic attack can occur at the oxygen atom of a bridging carbonyl. Thus AlBr3 may react with a linear carbonyl ligand of Ru3(CO)i2 which becomes bridged  

Similarly a proton can attack at the oxygen atom of a bridging carbonyl  

No significant examples of electrophilic attack on. ///-pyrrolizincs were reported since CHEC-II(1996). Nevertheless, treatment of the tricyclic pyrrolizine 53 with aqueous bromine in THF afforded, as expected, the corresponding bromohydrin 54 1997T4549 . 

Electrophilic substitutions at the pyrrole nucleus were described only with 1,2-dihydropyrrolizines which react with the same regioselectivity as would do equivalently substituted monocyclic pyrroles. 

The same authors 2000J(P1)3584 studied the reactivity of 2 toward benzenediazonium (chloride or tetrafluoro-borate) salts. No diazo coupling took place under neutral or slightly acidic conditions. However, under basic conditions (NaOH in H20/MeOH), a mixture of 62 and 63 was obtained. This result clearly indicates that the diazo coupling takes place through the anion of 62 which arises from the base-catalyzed methanolysis of amide 2 in which the pyrrole ring is obviously not nucleophilic enough. 

Since 3H-pyrrolizines are vinylpyrroles, a high reactivity towards electrophiles is to be expected. Because of the instability of pyrrolizines, electrophilic reactions have only rarely been translated into synthetically useful processes. 

In dilute acids, pyrrolizines are generally unstable. Protonation of 3H-pyrrolizine (1) in concentrated sulfuric acid however, could be achieved yielding a mixture of 45 /o (18a) and 55% (18b) 

The Vilsmeier reaction has attracted some attention as a route to cyclazines. 3H-pyrrolizine (1) gave the Vilsmeier salt (19a) on treatment with dimethylformamide and phosphoryl chloride at — 60°C. A second formylation to (20a) was achieved by treatment of (19a) with dimethyl-thioformamide and acetic anhydride 80JCS(P1)1319 . Similar products were obtained from a chloro-formylation of the ketone (3a) the Vilsmeier reaction at — 50°C gave the salt (19b) in 65% yield. From a reaction at 0 °C, 91 % of the trisubstituted derivative (21) was obtained, which was hydrolysed 

Acyl derivatives are formed in a reaction of 3H-pyrrolizine (1) with dichloroketene ketones (23) were formed depending on the conditions used. Ketones (23b) and (23c) could be obtained in good yields from (1) and the appropriate acid chloride in ether in the presence of anhydrous potassium carbonate, but the 2-acetyl derivative (23a) could not be obtained in this way 82JCR(S)54 . 

The oxime (24) produced from 3H-pyrrolizine (1) with amyl nitrite is probably formed by electrophilic attack 68CB3843 . 

Extended Hiickel M.O. calculations suggest that the regioselectivity of electrophilic attack upon the arene ligand in [Cr(CO)3(T]-arene)] complexes is controlled not only by the ring substituent, but also by the conformation of the Cr(CO)3 unit. Electrophilic substitution is preferred at arene carbons which are staggered with respect to the carbonyl groups. 

Kinetic studies have been made of the reactions of dimetal carbonyls of the type [M2(CO)io L ] (M2 = Mn2, MnRe, Re2 n = 1 or 2 L = range of tertiary phosphines and phosphites) with bromine and iodine in cyclohexane or de-calin. Complex rate laws were obtained, usually in the iodine case containing a predominant kih] term, but a term as high as [12] was obtained in one case. The influence of L on the rate constants for both I2 and Br2 reactions was best interpreted in terms of initial electrophilic attack at the O atom of the CO ligands. Rates increased in the order Mn2 MnRe Re2. 

Homogeneous Catalysis of Organic Reactions by Complexes of Metal Ions 

In general terms, highly fluorinated aUcenes are relatively resistant to attack by the types of reactant that are normally considered to be electrophilic in character [55, 153-155]. When one or more perfluoroaUcyl groups are attached to the double bond, then the system 

A variety of interesting electrophilic addition processes have been developed, where additions (where the electrophile is, for example. Cl, Br, I, NO2, -OCH2-, CH2NH2, CH2OH etc.) to fluoroalkenes are achieved by reaction with a series of reagents (Table 7.8). 

Tetrafluoroallene is interesting in that, in addition to its susceptibility towards nucleophilic attack discussed earlier, the compound also reacts readily with anhydrous hydrogen 

The iron complexes show two-fold reactivity. They react with both strong electrophiles and with strong nucleophiles as the iron can stabilize both the cationic and anionic intermediates. While the electron-withdrawing iron moiety activates the diene to nucleophilic attack, it deactivates it towards electrophilic attack. Electrophilic attack is still useful - the iron stabilizes the diene to all the side reactions that could go along with electrophilic attack, and stabilizes the cationic product. 

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A is a parameter that can be varied to give the correct amount of ionic character. Another way to view the valence bond picture is that the incorporation of ionic character corrects the overemphasis that the valence bond treatment places on electron correlation. The molecular orbital wavefimction underestimates electron correlation and requires methods such as configuration interaction to correct for it. Although the presence of ionic structures in species such as H2 appears coimterintuitive to many chemists, such species are widely used to explain certain other phenomena such as the ortho/para or meta directing properties of substituted benzene compounds imder electrophilic attack. Moverover, it has been shown that the ionic structures correspond to the deformation of the atomic orbitals when daey are involved in chemical bonds. 

Hiiekel m.o. ealenlations fail badly with benzimidazole. Loealisation energies for the free base and the eation indicated C(4) to be the most reactive position towards electrophilic attack, - and led to the false conclusion that substitution involved the free base, the orientation being controlled by charge densities. 

It is noteworthy that the compounds which have been shown to undergo extensive acetoxylation or side-chain nitration, viz. those discussed above and hemimellitene and pseudocumene (table 5.4), are all substances which have an alkylated ring position activated towards electrophilic attack by other substituents. 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

As illustrated in Scheme 8.1, both 2-vinylpyrroles and 3-vinylpyiroles are potential precursors of 4,5,6,7-tetrahydroindolcs via Diels-Alder cyclizations. Vinylpyrroles are relatively reactive dienes. However, they are also rather sensitive compounds and this has tended to restrict their synthetic application. While l-methyl-2-vinylpyrrole gives a good yield of an indole with dimethyl acetylenedicarboxylate, ot-substitiients on the vinyl group result in direct electrophilic attack at C5 of the pyrrole ring. This has been attributed to the stenc restriction on access to the necessary cisoid conformation of the 2-vinyl substituent[l]. 

An interesting rearrangement of the (4-methyl-2-thiazolyl)thioureas (263) has recently been reported (Scheme 160) (303). The reaction mechanism is currently under investigation. This reaction does not occur if the 4-methyl substituent in the thiazole ring of 263 is replaced by an hydrogen, which suggests an electrophilic attack on C-5 as the mechanism of this reaction. 

Electrophilic attack on the 5-position gives formation of an azomethinic bond and elimination of a molecule of water. 

Despite its V excessive character (340), thiazole, just as pyridine, is resistant to electrophilic substitution. In both cases the ring nitrogen deactivates the heterocyclic nucleus toward electrophilic attack. Moreover, most electrophilic substitutions, which are performed in acidic medium, involve the protonated form of thiazole or some quaternary thiazolium derivatives, whose reactivity toward electrophiles is still lower than that of the free base. 

Because electrophilic attack on benzene is simply another reaction available to a carbocation other carbocation precursors can be used m place of alkyl halides For exam pie alkenes which are converted to carbocations by protonation can be used to alkyl ate benzene... 

A methyl group is an electron releasing substituent and activates all of the ring carbons of toluene toward electrophilic attack The ortho and para positions are activated more than the meta positions The relative rates of attack at the various positions m toluene compared with a single position m benzene are as follows (for nitration at 25°C)... 

Comparable stabilization of the intermediate leading to meta substitution is not possible Thus resonance involving halogen lone pairs causes electrophilic attack to be favored... 

Because the position of electrophilic attack on an aromatic nng is controlled by the direct ing effects of substituents already present the preparation of disubstituted aromatic com pounds requires that careful thought be given to the order of introduction of the two groups Compare the independent preparations of m bromoacetophenone and p bromoace tophenone from benzene Both syntheses require a Friedel-Crafts acylation step and a bromination step but the major product is determined by the order m which the two steps are carried out When the meta directing acetyl group is introduced first the final product IS m bromoacetophenone... 

Polycyclic aromatic hydrocarbons undergo electrophilic aromatic substitution when treated with the same reagents that react with benzene In general polycyclic aromatic hydrocarbons are more reactive than benzene Most lack the symmetry of benzene how ever and mixtures of products may be formed even on monosubstitution Among poly cyclic aromatic hydrocarbons we will discuss only naphthalene and that only briefly Two sites are available for substitution m naphthalene C 1 and C 2 C 1 being normally the preferred site of electrophilic attack... 

C 1 IS more reactive because the intermediate formed by electrophilic attack there IS a relatively stable carbocation A benzene type pattern of bonds is retained m one nng and the positive charge is delocalized by allylic resonance... 

The regioselectivity of substitution in furan is explained using a resonance descrip tion When the electrophile attacks C 2 the positive charge is shared by three atoms C 3 C 5 and O... 

When the electrophile attacks at C 3 the positive charge is shared by only two atoms C 2 and O and the carbocation intermediate is less stable and formed more slowly... 

Wnte a structural formula for the most stable cyclohexadienyl cation intermediate formed in each of the following reactions Is this intermediate more or less stable than the one formed by electrophilic attack on benzene" ... 

Many of the properties of phenols reflect the polarization implied by the resonance description The hydroxyl oxygen is less basic and the hydroxyl proton more acidic in phenols than m alcohols Electrophiles attack the aromatic ring of phenols much faster than they attack benzene indicating that the ring especially at the positions ortho and para to the hydroxyl group is relatively electron rich... 

Although a hydroxyl group strongly activates an aromatic ring toward electrophilic attack an oxyanion substituent is an even more powerful activator Electron delocaliza tion m phenoxide anion leads to increased electron density at the positions ortho and para to oxygen... 

Electron distribution governs the electrostatic potential of molecules. The electrostatic potential describes the interaction of energy of the molecular system with a positive point charge. Electrostatic potential is useful for finding sites of reaction in a molecule positively charged species tend to attack where the electrostatic potential is strongly negative (electrophilic attack). 

In this example, the HOMO is plotted one Angstrom above the plane of the molecule. Since it is of n symmetry, it has a node in the plane of the molecule. It shows the site of electrophilic attack at the carbon adjacent to the oxygen atom. This is also the experimentally observed site. The orbital comes from an Extended Hiickel calculation of an MM-t optimized geometry. 

Electrophilic Reactions. Perfluoroepoxides are quite resistant to electrophilic attack. However, they react readily with Lewis acids, for example SbF, to give ring-opened carbonyl compounds (20—22) (eq. 2). 

Electrophilic Aromatic Substitution. The Tt-excessive character of the pyrrole ring makes the indole ring susceptible to electrophilic attack. The reactivity is greater at the 3-position than at the 2-position. This reactivity pattern is suggested both by electron density distributions calculated by molecular orbital methods and by the relative energies of the intermediates for electrophilic substitution, as represented by the protonated stmctures (7a) and (7b). Stmcture (7b) is more favorable than (7a) because it retains the ben2enoid character of the carbocycHc ring (12). 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

The first step in the catalytic alkylation of aromatics is the conversion of an olefin or olefin-producing reagent into a carbonium ion or polari2ed complex. Then, this carbonium ion or complex, which is a powerful electrophile, attacks the aromatic ring (32). 

Electrophilic Attack at Nitrogen. The lone pair on pyridiae (1) = 5.22) reacts with electrophiles under mild conditions, with protonic... 

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