Tt excessive heterocycles

The tremendous difference in reactivity towards electrophiles, that distinguishes ir-deficient and tt-excessive heterocycles, is considerably diminished for nucleophilic substitution reactions in which ring... 

V-Alkyl TT-excessive heterocycles such as pyrazoles, imidazoles and triazoles can be lithiated. In the example shown in Scheme 34, lithiation occurs selectively on the N-methyl in preference to the C-methyl (azaenolate). ... 

Like pyrrole, indole is a very reactive tt-excessive heterocycle and reacts with halogens and other electrophiles extremely rapidly [1], Nature has exploited this property to produce more than 300 halogenated indoles, mainly bromoindoles in marine organisms. A few examples are illustrated below. Chapter 2 contains references to reviews of these natural organohalogens. 

Positional selectivity in electrophilic substitution reactions of Tt-excessive heterocycles 12KGS256. 

It is convenient to consider heteroaromatic ligands in two classes - 7t-excessive, five membered rings typified by pyrrole, furan and thiophen, and TC-deficient six-membered rings typified by pyridine. The 7i-excessive heterocycles are usually extremely reactive towards electrophilic attack and, with the exception of thiophen, do not exhibit the chemical inertness often associated with aromatic benzene derivatives. Conversely, the TT-deficient heterocycles are extremely inert with respect to electrophilic attack. Paradoxically, it is the high reactivity of the five-membered rings and the inertness of the six-membered rings that give rise to common synthetic problems. The usual methods for the... 

The TT-excessive five-membered ring heterocycles furan, pyrrole, and N-methylpyrrole add readily to C-7 of DNBF to yield the C(a) adducts 27... 

The heteroaromatic compounds can be divided into two broad groups, called tt excessive and tt deficient, depending on whether the heteroatom acts as an electron donor or electron acceptor. Furan, pyrrole, and thiophene, as well as other heterocyclics incorporating an oxygen, nitrogen, or sulfur atom that contributes two tt electrons are in the Tr-excessive group. This classification is indicated by resonance structures and has been confirmed by various MO methods. ... 

MOs 7T2 and t3, as well as t4 und tts, are energetically inequivalent (see Fig. 5.2b and c), contrary to the fact that the carbocycles benzene and the cyclopentadienyl anion are iso- -electronic with furan. Because the nodal plane of 773 passes through the heteroatom, in contrast to that of the degeneracy is lost. Every C-atom contributes one electron and the 0-atom two electrons to the cyclic conjugated structure. The six electrons occupy the three bonding tt-MOs in pairs. As there are six electrons distributed over five atoms, the r-electron density on each ring atom is greater than one (see Fig. 5.2). Furan is thus a TT-electron excessive heterocycle. 

We also were successful in applying the alkyl nitrate nitration to TT-deficient heterocyclic compounds such as 2- and 4-meth-ylpyridines, 4-methyl pyrimidine, and to ir-excessive heterocyclics such as 2-methylbenzoxazole and 2-methylbenzothiazole (15). Both sodium and potassium amides in liquid ammonia were found to be effective as bases. In the KNH2-JI.NH3 system optimum yields are obtained if the molar ratio of base to substrate to nitrate ester is 2.0 1.0 2.5. After allowing 2-3 minutes for anion formation the nitrate ester is added as rapidly as possible while maintaining the temperature below -33°. Next the ammonia is replaced with ether and the nitro salt filtered off and acidified with aqueous acetic acid. 

C.i.d. Heck Reaction. 7r-Deflcient chloropyrazines can be Heck-coupled into 1,3-azoles (Scheme 50). It will be recalled that the same methodology was used to couple into the TT-excessive furan, thiophene, and pyrrole heterocycles and their benzo derivatives (vide supra). The Heck reaction in oxazole and thiazole proceeds in a regiospeciflc manner. The new carbon-carbon bond is formed in the 5-position 117 next to the ether heteroatom as commonly observed in vinyl ethers and strongly favored in furan and thiophene. In benzoxazole and benzothiazole the only vacant position is between the two heteroatoms, and the Heck coupling results in substitution into the 2-position 118. " ... 

Thiadiazole, like its structural isomer 1,2,3-thiadiazole, is aromatic and is to be regarded as a 7t-excessive heterocycle, with relatively 7t-deficient C-atoms. The tt-electron density calculated by the HMO method is lowest on C-5 (0.7888). Therefore, nucleophiles attack in this position. 

A wide variety of cyclic S-N compounds containing two or three coordinate sulfur is known (i ), The binary S-N rings vary in size from four (S2N2) to ten (SsNs" ") atoms and examples of anions (SsNs") and cations (S3N2 , S N3 , S N ) are known in addition to neutral molecules (2). The excess of electrons in these planar, electron-rich heterocycles is often accommodated in low lying tt orbitals but, in some cases (e.g. S N, S Ns"), the number of tt electrons is reduced by formation of transannular S-S bonds to give cages ( , ). 

The TT-electron excess of the five-membered rings is accompanied by a high rr-donor character. The best measure of rr-donation is the value of first ionization potential, IP, which for all aromatic heterocycles with one heteroatom of pyrrole type reflects the energy of highest occupied rr-orbital. IP, values decrease in the sequence pyrrole > indole > carbazole furan > benzo[/ ]furan > dibenzofuran thiophene > benzo[/ ]thiophene (Section 2.3.3.9, Tables 21 and 23). Thus, the more extensive the rr-system, the stronger is its electron donor ability. Furan and thiophene possess almost equal rr-donation, which is considerably lower than that of pyrrole. 

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