Electrophilic substitution carbon

Electrophilic substitution of thianthrene takes place at C-2. No examples of even minor amounts of 1-mono-substituted product have been reported. Disubstitution gives 2,7- (usually) or 2,8-products. In a few cases, 2,6-derivatives have been claimed. The presence of a sulfoxide or sulfone unit greatly reduces the susceptibility of either ring to electrophilic substitution. Carbon-centered electrophilic addition to sulfur to produce 5-R-thianthrenium salts has been described rarely most examples of the formation of such salts have involved the thianthrene radical ion(l-t-). Treatment of thianthrene with alkyl/aryllithiums produces the 1-lithio-species, and these organometallic derivatives allow the introduction of substituents at this position. 

At one time a form of 8 2 mechanism was favoured for electrophilic substitution in which in the transition state bonding between carbon and the electrophile and severance of the proton had proceeded to the... 

The heats of formation of Tt-complexes are small thus, — A//2soc for complexes of benzene and mesitylene with iodine in carbon tetrachloride are 5-5 and i2-o kj mol , respectively. Although substituent effects which increase the rates of electrophilic substitutions also increase the stabilities of the 7r-complexes, these effects are very much weaker in the latter circumstances than in the former the heats of formation just quoted should be compared with the relative rates of chlorination and bromination of benzene and mesitylene (i 3 o6 x 10 and i a-Sq x 10 , respectively, in acetic acid at 25 °C). 

M.o. theory and the transition state treatment In 1942 Wheland proposed a simple model for the transition state of electrophilic substitution in which a pair of electrons is localised at the site of substitution, and the carbon atom at that site has changed from the sp to the sp state of hybridisation. Such a structure, originally proposed as a model for the transition state is now known to describe the (T-complexes which are intermediates in electrophilic substitutions... 

The occurrence of a hydrogen isotope effect in an electrophilic substitution will certainly render nugatory any attempt to relate the reactivity of the electrophile with the effects of substituents. Such a situation occurs in mercuration in which the large isotope effect = 6) has been attributed to the weakness of the carbon-mercury bond relative to the carbon-hydrogen bond. The following scheme has been formulated for the reaction, and the occurrence of the isotope effect indicates that the magnitudes of A j and are comparable ... 

The problem of electrophilic substitution into the anilinium ion has been examined by the methods of m.o. theory. Attempts to simulate the --inductive effect in Hiickel M.o. theory by varying the Coulomb integral of C(j) (the carbon atom to which the NH3+ group is attached) remove 7r-electrons from the o- and -positions and add them to the... 

Reactivity of A-4-thiazoline-2-thiones and derivatives involves four main possibilities nucleophilic reactivity of exocyclic sulfur atom or ring nitrogen, electrophilic reactivity of carbon 2 and electrophilic substitution on carbon 5. 

Iron Porphyrins. Porphyrias (15—17) are aromatic cycHc compouads that coasist of four pyrrole units linked at the a-positions by methine carbons. The extended TT-systems of these compounds give rise to intense absorption bands in the uv/vis region of the spectmm. The most intense absorption, which is called the Soret band, falls neat 400 nm and has 10. The TT-system is also responsible for the notable ring current effect observed in H-nmr spectra, the preference for planar conformations, the prevalence of electrophilic substitution reactions, and the redox chemistry of these compounds. Porphyrins obtained from natural sources have a variety of peripheral substituents and substitution patterns. Two important types of synthetic porphyrins are the meso-tetraaryl porphyrins, such as 5,10,15,20-tetraphenylporphine [917-23-7] (H2(TPP)) (7) and P-octaalkylporphyrins, such as 2,3,7,8,12,13,17,18-octaethylporphine [2683-82-1] (H2(OEP)) (8). Both types can be prepared by condensation of pyrroles and aldehydes (qv). 

Electrophilic Substitution. The most common mechanism for electrophilic attack at an aromatic system involves the initial attack of an electrophile to give an intermediate containing a tetrahedral carbon atom loss of, usually a proton, from the intermediate, then gives the product ... 

The precise numerical values of the calculated electron densities are unimportant, as the most important feature is the relative electron density thus, the electron density at the pyrazine carbon atom is similar to that at an a-position in pyridine and this is manifest in the comparable reactivities of these positions in the two rings. In the case of quinoxaline, electron densities at N-1 and C-2 are proportionately lower, with the highest electron density appearing at position 5(8), which is in line with the observation that electrophilic substitution occurs at this position. 

It is also of significance that in the dilute gas phase, where the intrinsic orientating properties of pyrrole can be examined without the complication of variable phenomena such as solvation, ion-pairing and catalyst attendant on electrophilic substitution reactions in solution, preferential /3-attack on pyrrole occurs. In gas phase t-butylation, the relative order of reactivity at /3-carbon, a-carbon and nitrogen is 10.3 3.0 1.0 (81CC1177). 

An alternative approach is in terms of frontier electron densities. In electrophilic substitution, the frontier electron density is taken as the electron density in the highest filled MO. In nucleophilic substitution the frontier orbital is taken as the lowest vacant MO the frontier electron density at a carbon atom is then the electron density that would be present in this MO if it were occupied by two electrons. Both electrophilic and nucleophilic substitution thus occur at the carbon atom with the greatest appropriate frontier electron density. 

A multiply bonded nitrogen atom deactivates carbon atoms a or y to it toward electrophilic attack thus initial substitution in 1,2- and 1,3-dihetero compounds should be as shown in structures (110) and (111). Pyrazoles (110 Z = NH), isoxazoles (110 Z = 0), isothiazoles (110 Z = S), imidazoles (111 Z = NH, tautomerism can make the 4- and 5-positions equivalent) and thiazoles (111 Z = S) do indeed undergo electrophilic substitution as expected. Little is known of the electrophilic substitution reactions of oxazoles (111 Z = O) and compounds containing three or more heteroatoms in one ring. Deactivation of the 4-position in 1,3-dihetero compounds (111) is less effective because of considerable double bond fixation (cf. Sections 4.01.3.2.1 and 4.02.3.1.7), and if the 5-position of imidazoles or thiazoles is blocked, substitution can occur in the 4-position (112). 

In compounds with a fused benzene ring, electrophilic substitution on carbon usually occurs in the benzenoid ring in preference to the heterocyclic ring. Frequently the orientation of substitution in these compounds parallels that in naphthalene. Conditions are often similar to those used for benzene itself. The actual position attacked varies compare formulae (341)-(346) where the orientation is shown for nitration sulfonation is usually similar for reasons which are not well understood. 

In still other cases, the product of reaction of an electrophile with an aminoazole is from electrophilic attack at a ring carbon. This is electrophilic substitution and is the general result of nitration and halogenation (see Section 4.02.1.4). In such cases, reactions at both cyclic nitrogen and at an amino group are reversible. 

The acid-catalyzed additions of bromide and chloride ion to thiiranes occurs readily, with halide preferentially but not exclusively attacking the most substituted carbon atom of the thiirane. The reaction of 1-substituted thiiranes with acetyl chloride shows a slight preference for halide attack at the less substituted carbon atom (80MI50601). For further discussion of electrophilic catalysis of halide ion attack see Section 5.06.3.3.2. The reaction of halogens with thiiranes involves electrophilic attack on sulfur (Section 5.06.3.3.6) followed by nucleophilic attack of halide ion on carbon. 

Both HMO calculations and more elaborate MO methods can be applied to the issue of the position of electrophilic substitution in aromatic molecules. The most direct approach is to calculate the localization energy. This is the energy difference between the aromatic molecule and the n-complex intermediate. In simple Hiickel calculations, the localization energy is just the difference between the energy calculated for the initial n system and that remaining after two electrons and the carbon atom at the site of substitution have been removed from the conjugated system ... 

The general mechanism for electrophilic substitution suggests that groups other than hydrogen could be displaced, provided the electrophile attacked at the substituted carbon. Substitution at a site already having a substituent is called ipso substitution and has been observed in a number of circumstances. The ease of removal of a substituent depends on its ability to accommodate a positive charge. This fector determines whether the newly attached electrophile or the substituent is eliminated from the [Pg.588]

During indolization of the 3, 6 and 7-quinolylhydrazones, formation of the new C-C bond occurs between the appropriate carbon atom of the ketone/aldehyde moiety and the 4, 5 and 8 carbon atoms of the quinoline nucleus. It is consistent with the mechanism of formation of the C-C bond during indolization and the direction of electrophilic substitution in the quinoline nucleus. °... 

Thus attack of the TosMlC anion 9 on a carbonyl carbon is followed (or accompanied) by ring closure of the carbonyl oxygen to the electrophilic isocyano carbon to form an oxazoline (12). Loss of p-tolylsulfinic acid provides the 5-substituted oxazole 13. ... 

Several calculations of the electronic structure of isoindoles have Ijeen published, and the distribution of charge density around the isoindole nucleus calculated by these methods is summarized in X able I. A common prediction of the calculations, which are based on tlie LCAO-MO method or the frontier electron concept, is the relatively high electron density to bo found at position 1, and the expectation, thei efore, i.s that electrophilic substitution on carbon... 

No example of electrophilic substitution at ring carbon atoms has been reported. 

Phospholes and analogs offer a wide variety of coordination modes and reactivity patterns, from the ti E) (E = P, As, Sb, Bi) through ri -dienic to ri -donor function, including numerous and different mixed coordination modes. Electrophilic substitution at the carbon atoms and nucleophilic properties of the phosphorus atom are well documented. In the ri -coordinated species, group V heteroles nearly acquire planarity and features of the ir-delocalized moieties (heterocymantrenes and -ferrocenes). 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

The opposite case—reaction of an arenediazonium species with an aliphatic substrate —is possible if a sufficiently acidic C—H bond is present e.g. with /3-keto esters and malonic esters. The reaction mechanism is likely to be of the Sel-type an electrophilic substitution at aliphatic carbon ... 

Figure 16.10 Biosynthesis of phylloquinone (vitamin K-j) from 1,4-dihydroxynaphthoic acid. The key step that joins the 20-carbon phytyl side chain to the aromatic ring is a Friedel-Crafts-like electrophilic substitution reaction.

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pKa of the pyrrolin-ium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted previously in Section 15.5, is that pyrrole has six 77 electrons and is aromatic. Each of the four carbons contributes one... 

A short digression is in order at this juncture. The electrophilic substitution of a vinylsilane is a very useful process because it is generally both regio- and stereospecific. The carbon-silicon bond is strongly polarized due to the high electronegativity of carbon (2.35) relative to silicon (1.64).67b A unique and important conse-... 

The C6 position of a V,./V-dialkyl-3//-azepin-2-amine, e.g. 1, displays remarkable reactivity towards electrophilic substitution, and with dimethyl(methylsulfanyl)sulfonium tetrafluorobor-ate undergoes methylsulfanylation and quaternization to yield 6-(methylsulfanyl)-3//-azepin-ium tetrafluoroborates, e.g. 2, identical to those obtained by quaternization of the free bases with trityl tetrafluoroborate.64 Basification of the salts with potassium carbonate yields the free bases, e.g. 3, which decompose during distillation or on exposure to air. 

Several chlorophyll derivatives have been prepared by electrophilic substitution, inter alia by formylation reactions. Adopting methods from corrin chemistry.50 alkylation with chloro-methyl methyl ether (caution toxic),32k chloromethyl methyl sulfide,51 and dichloromethyl methyl ether (caution toxic)52 in the presence of Lewis acids are the methods of choice to introduce carbon residues into the chlorin frame work. The compounds listed below have been prepared by these methods. 

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