Imidazoles, aromaticity

The reaction of pentafluoroiodobenzene with aromatic compounds such as anilines, pyrroles, indoles, imidazoles, aromatic ethers and phenols leads to aryl—aryl coupling477. The reactions proceed via pentafluorophenyl radicals which are generated by photoin-duced electron transfer (PET) and loss of iodide ion. Coupling between the pentafluorophenyl radical and the radical cation of the donor gives biaryl cations (138,139) which lose a proton. The reaction is illustrated for N, A-dimethylaniline (equation 125). 

Imidazole aromaticity minimizes resonance donation by nitrogen... 

STRATEGY AND ANSWER When imidazole accepts a proton at N3 the electron pair that accepts the proton is not a part of the tt system of six electrons that makes imidazole aromatic. Consequently, the conjugate base that is formed is still aromatic (it is an aromatic cation) and retains its resonance energy of stabilization. 

The Fe-N mode is at 222 in the R state and 207 cnY in the T state for the a subunits, but only shifted to 218 T state for the (3 subunits. This is consistent with the interpretation that the Fe-imidazole interations are weakened more in the T state of the a subunits than p subunits. Time-resolved resonance Raman studies have shown that the R T switch is complete on a 10 ps tuuescale [38]. Finally, UV excitation of the aromatic protein side chains yields... 

Comparative studies have been undertaken between different heterocyclic series, especially the azoles, thiazoles. oxazoles. imidazoles, and selenazoles. In a large number of these studies, the heterocycles are condensed w ith aromatic nuclei. 

Imidazole and its derivatives form an interesting and important class of hetero cyclic aromatic amines Imidazole is approximately 100 times more basic than pyndme... 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

The compounds of this article, ie, ftve-membered heterocycles containing two adjacent nitrogen atoms, can best be discussed according to the number of double bonds present. Pyrazoles contain two double bonds within the nucleus, imparting an aromatic character to these molecules. They are stable compounds and can display the isomeric forms, (1) and (2), when properly substituted. Pyrazoles are scarce ia nature when compared to the imidazoles (3), which are widespread and have a central role ia many biological processes. 

The carbon atoms of azole rings can be attacked by nucleophilic (Section 4.02.1.6 electrophilic (Section 4.02.1.4) and free radical reagents (Section 4.02.1.8.2). Some system for example the thiazole, imidazole and pyrazole nuclei, show a high degree of aromati character and usually revert to type if the aromatic sextet is involved in a reaction. Othei such as the isoxazole and oxazole nuclei are less aromatic, and hence more prone to additio reactions. 

The distinction between these two classes of reactions is semantic for the five-membered rings Diels-Alder reaction at the F/B positions in (269) (four atom fragment) is equivalent to 1,3-dipolar cycloaddition in (270) across the three-atom fragment, both providing the 47t-electron component of the cycloaddition. Oxazoles and isoxazoles and their polyaza analogues show reduced aromatic character and will undergo many cycloadditions, whereas fully nitrogenous azoles such as pyrazoles and imidazoles do not, except in certain isolated cases. 

The 3H- and 4//-pyrazoles and 2H- and 4//-imidazoles (83UP40200) contain two doable bonds in the heterocyclic ring, but in each case the conjugation does not include all the ring atoms hence the compounds are not aromatic. 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

The systems discussed here are aromatic systems which undergo a variety of isomerizations on irradiation. Irradiation of imidazoles led to a scrambling of substituents, whereas such scrambling has not been observed in the pyrazoles which undergo photoisomerization to imidazoles. 

Sulfonamides (R2NSO2R ) are prepared from an amine and sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Arylsulfonamides are stable to alkaline hydrolysis, and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, and by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than are those of the more basic alkyl amines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic — NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing proj>erty of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Perfluoroalkylation of substituted benzenes and heterocyclic substrates has been accomplished through thermolysis of perfluoroalkyl iodides in the presence of the appropriate aromatic compound Isomeric mixtures are often obtained W-Methylpyrrole [143] and furan [148] yield only the a-substituted products (equation 128) Imidazoles are perfluoroalkylated under LTV irradiation [149] (equation 129). 4-Perfluoroalkylimidazoles are obtained regioselectively by SET reactions of an imidazole anion with fluoroalkyl iodides or bromides under mild conditions [150] (equation 130) (for the SET mechanism, see equation 57)... 

Pyridine and imidazole were two of the heterocyclic aromatic compounds described in Section 11.22. 

The pyrimidine ring system is planar, while the purine system deviates somewhat from planarity in having a slight pucker between its imidazole and pyrimidine portions. Both are relatively insoluble in water, as might be expected from their pronounced aromatic character. 

PROTECTION FOR IMIDAZOLES, PYRROLES, INDOLES, AND OTHER AROMATIC HETEROCYCLES... 

Cyclohexadiene, Pd-black, 25°, 100% yield, imidazole = His(Bn). With H2/Pd-C, the normal conditions for benzyl group removal, it is difficult to remove the benzyl group on histidine without also causing the reduction of other aromatic groups that may be present. ... 

In addition, demercuriation reactions have resulted in a wide variety of rather complex compounds including aromatic aminoacids, steroids, imidazols, etc. in good yields (at the tracer level). The driving force in these studies has been the hope of incorporating At into biologically active compounds for therapautic use. 

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