Pyrazoles Imidazoles

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

In azole chemistry the total effect of the several heteroatoms in one ring approximates the superposition of their separate effects. It is found that pyrazole, imidazole and isoxazole undergo nitration and sulfonation about as readily as nitrobenzene thiazole and isothiazole react less readily ica. equal to m-dinitrobenzene), and oxadiazoles, thiadiazoles, triazoles, etc. with great difficulty. In each case, halogenation is easier than the corresponding nitration or sulfonation. Strong electron-donor substituents help the reaction. 

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

Major advancements in the chemistry of pyrazoles, imidazoles, triazoles, tetrazoles, and related fused heterocyclic derivatives continued in 2000. Solid-phase combinatorial chemistry of pyrazoles and benzimidazoles has been particularly active. Synthetic routes to all areas continue to be pursued vigorously with improvements and applications. Notably, metal-promoted and cross-coupling reactions of all classes seemed to be a dominant theme in 2000. Applications of pyrazole-, imidazole-, and 1,2,3-benzotriazole-containing reagents to a wide array of synthetic applications remained active. 

Nitrile oxides add to various N-nucleophiles, bearing N-H bonds to give amidoximes. These nucleophiles comprise primary and secondary amines, amides, N-heterocycles and so on. Thus, N-unsubstituted pyrazole, imidazole, 1,2,3- and... 

Furan Thiophene Pyrrole Pyrazole Imidazole Thiazole... 

In the last ten years extensive studies of homolytic arylation have been made in the following heterocyclic series furan, thiophene, thiazole, isothiazole, pyrazole, imidazole, ... 

Photolysis of azolediazonium tetrafluoroborates, by the method of Kirk and Cohen (73JA4619), is a general reaction in the pyrazole, imidazole, benzimidazole and triazole series and is of synthetic interest to obtain fluoroazoles. 

Some earlier contradictory results concerning the reactions of N-unsubstituted azoles have been clarified (224,225) and it has been shown that pyrazole, imidazole, 1,2,4-triazole, and benzotriazole all undergo nucleophilic addition to give (e.g., 392) from pyrazole and 373 (R, R =Ph). 

An alternate approach for the 1-arylation of pyrroles is offered by their copper catalyzed coupling with aryl bromides and iodides, as depicted in 6.68. The process, run in the presence of trans-N,N -dnnethyl-cyclohcxane-diamine, was also efficient in the A-arylation of pyrazole, imidazole, triazoles and indazole, giving a mixture of isomers in the latter case.100... 

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... 

Pyrazole Imidazole v-Triazole s-Tri azole Tetrazole Equivalent Equivalent 1,2,5 > 1,2,3 1.2.4 > 1,3,4 1.2.3.4 > 1,2,3,5 b Electron-withdrawing group prefers 3-position Electron-withdrawing group prefers 4-position... 

Azoles containing a free NH group react comparatively readily with acyl halides. yV-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (75) — (76) or type (79)—>(80) or (81). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. 

Electrophilic substitution occurs readily in iV-phenyl groups, e.g., 1-phenyl-pyrazoles, -imidazoles and -pyrazolinones are all nitrated and halogenated at the para position. The aryl group is attacked preferentially when the reactions are carried out in strongly acidic media where the azole ring is protonated. 

Isoxazolc Oxazole Isothiazole Thiazole Pyrazole Imidazole ... 

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