1,3-dipoles aromatic heterocycles

Cycloaddition with nitrile oxides occur with compounds of practically any type with a C=C bond alkenes and cycloalkenes, their functional derivatives, dienes and trienes with isolated, conjugated or cumulated double bonds, some aromatic compounds, unsaturated and aromatic heterocycles, and fullerenes. The content of this subsection is classified according to the mentioned types of dipolarophiles. Problems of relative reactivities of dienophiles and dipoles, regio- and stereoselectivity of nitrile oxide cycloadditions were considered in detail by Jaeger and... 

Many mesoionic substances (2.6) can act as 1,3-dipoles, and, after elimination of a small molecule -carbon dioxide in the example shown - produce aromatic heterocycles. ... 

The MM3 force field has been extended by Allinger and co-workers to cover aromatic heterocycles of the pyridine and pyrrole types <93JA11906>. Structures (32 compounds), dipole moments (35 compounds), heats of formation (35 compounds), and vibrational spectra (11 compounds) were examined. The results are good for structure and fair for the other items resonance energies were reported for the series benzene (17.79 kcal mol ), pyridine (17.02 kcal mol ), pyridazine (14.35 kcal mol ), pyrazine (17.01 kcal mol ), pyrimidine (15.60 kcal mol ), 1,3,5-triazine (13.51 kcal mol ), and 1,2,4,5-tetrazine (17.72 kcal mol ). Finally, ab initio studies of the dipole polarizabilities of conjugated molecules have been reported in which monocyclic azines (pyridine, pyridazine, pyrimidine, pyrazine, 5-triazine, and 5-tetrazine) are compared <94JST(304)109>. 

The role of heteroatoms in ground- and excited-state electronic distribution in saturated and aromatic heterocyclic compounds is easily demonstrated by a comparison of a number of heteroaromatic systems with their perhydro counterparts. In Jt-excessive heteroaromatic systems, because of their resonance structures, their dipole moments are less in the direction of the heteroatom than in the corresponding saturated heterocycles furan (1, 0.71 D) vs. tetrahydrofliran (2, 1.68 D), thiophene (3, 0.52 D) vs. tetrahydrothiophene (4, 1.87 D), and selenophene (5, 0.40 D) vs. tetrahydroselenophene (6, 1.97 D). In the case of pyrrole (7, 1.80 D), the dipole moment is reversed and is actually higher than that of pyrrolidine (8, 1.57 D) due to the acidic nature of the pyrrole ring (the N-H bond) In contrast, the dipole moment of n-deficient pyridine (9, 2.22 D) is higher than that of piperidine (10, 1.17 D). In all these compounds, with the exception of pyrrole (7), the direction of the dipole moment is from the ring towards the heteroatom [32-34]. 

Because microwave spectroscopy is less commonly used for the determination of dipole moments of aromatic heterocycles than the dielectric constant methods, only a brief summary of the various modifications and possibilities will be presented here. 

The above material represents a concise overview devoted to experimental and theoretical dipole moments of aromatic heterocycles, their determination and computation. Only selected relevant references are included, with a particular attention to our own work. The coverage is not exhaustive. 

It is also clear that dipole moments still represent one of the important physical characteristics of compounds with an uneven distribution of charge in general and aromatic heterocycles in particular. 

Pyrrole is a five-membered aromatic heterocycle containing six n electrons. Five important resonance hybrid structures distribute the 7C-electron pair of the nitrogen atom over the four carbon atoms, and the dipole moment of pyrrole (1.84 daltons similar to water) in the gas phase is directed in a way to make the nitrogen atom the positive end of the dipole. Pyrrole carbon atoms are therefore extraordinarily rich in electrons (Gossauer, 1984). The H-NMR spectrum is of the expected AB type (Figure 6.2.1) the chemical shifts are similar to the ones of benzene. 

The reason why pyrrole is an QlQcixon-excessive aromatic heterocycle is because the electron density on each ring atom is greater than one. Pyrrole has a dipole moment of 1.55 D, similar to that of pyrrolidine in number although with opposite direction. (Here, the direction of the dipole moment vector is represented by an arrow and is properly defined so that the arrow is directed from the positive fractional charge to the negative fractional charge). 

The cydoaddition of different 1,3-dipoles such as azides [331, 341] and diazoalkanes [342-344] to acceptor-substituted allenes was thoroughly investigated early and has been summarized in a comprehensive review by Broggini and Zecchi [345], The primary products of the 1,3-dipolar cycloadditions often undergo subsequent fast rearrangements, for example tautomerism to yield aromatic compounds. For instance, the five-membered heterocycles 359, generated regioselectively from allenes 357 and diazoalkanes 358, isomerize to the pyrazoles 360 (Scheme 7.50) [331]. 

Nitrile oxides are widely used as dipoles in cycloaddition reactions for the synthesis of various heterocyclic rings. In order to promote reactions between nitrile oxides and less reactive carbon nucleophiles, Auricchio and coworkers studied the reactivity of nitrile oxides towards Lewis acids. They observed that, in the presence of gaseous BF3, nitrile oxides gave complexes in which the electrophilicity of the carbon atom was so enhanced that it could react with aromatic systems, stereoselectively yielding aryl oximes 65 and 66 (Scheme 35). ... 

Mesoionic compounds have been known for many years and have been extensively utilized as substrates in 1,3-dipolar cycloadditions.158-160 Of the known mesoionic heterocycles, munchnones and sydnones have generated the most interest in recent years. These heterocyclic dipoles contain a mesoionic aromatic system i.e. 206) which can only be depicted with polar resonance structures.158 Although sydnones were extensively investigated after their initial discoveiy in 1935,160 their 1,3-dipolar character was not recognized until the azomethine imine system was spotted in the middle structure of (206). C-Methyl-N-phenylsydnone (206) combines with ethyl phenylpropiolate to give the tetrasub-... 

In other aromatic or heterocyclic compounds, the conjugation was not evaluated and dipole moments exploited only for determining conformation. Examples are fural and diformylfuran152 the preferred conformation was very near to free rotation. 

---