Syntheses of heterocyclic compounds. Part II. N-arylazoles by Ullmann condensation

Abstract

A number of N-arylazoles were prepared by the Ullmann condensation of various azoles with aryl halides in pyridine. by use of copper( 11) oxide as catalyst. 7001, AustraliaTHE condensation of five-membered heteroaromatic compounds containing a free NH group with aryl halides in the presence of a copper catalyst is related to analogous Ullmann condensations.2-* Some N-aryl heteroaromatic compounds were previously prepared by conducting such condensations in nitr~benzene.~-~ We have prepared various N-arylazoles by use of pyridine as solvent 9 in our condensations. The results are summarked in Tables 2-5;Table 6 contains analytical data for new compounds.Unactivated aryl halides (e.g. bromobenzene, iodobenzene, and 9-bromoanisole) did not arylate 1,2,4-triazole under the Ullmann conditions. Bright coloured solids were noticed in the reaction mixtures, indicating the formation of copper complexes. Similar difficulty was encountered in arylation of azoles by m-chloronitrobenzene in pyridine. Better yields of the arylated products in the o-nitrophenylation of most of the azoles seemed to be due to some special effect, such as ' built-in solvation.' 10Intermediates such as copper phenoxide (and a x-complex with copper phenoxide) and arylcopper have been postulated to take part in the Ullmann diary1 etherll and biaryl l2 syntheses, respectively, and since some of the azoles (benzimidazole, imidazole, and 1,2,4-triazole) are known to form complexes with copper salts13 it is likely that such an intermediate is also responsible for these arylations under Ullmann conditions. However, another mechanism, in which the potassium salt of a heteroaromatic compound reacts as its anion in a coppercatalysed nucleophilic substitution on the aryl halide ,14 can also explain the formation of N-arylazoles; all the azoles employed in the present work give metallic derivatives.

N-arylation of 3-alkoxypyrazoles, the case of the pyridines

“…Mp¼129 C. 1 Obtained in a 52% yield as a yellow solid after a chromatography over silica gel (dichloromethane-ethanol 96/4) if, as for compound 8a, the heating was shortened to 1 h and the temperature kept to 100 C. Mp¼206 C. 1 (9). Compound 4a (0.17 g, 0.97 mmol) was boiled in 2 N hydrochloric acid (15 mL) for 1 h. The resulting suspension was made basic with sodium hydrogencarbonate, and extracted with ethyl acetate.…”

“…[4][5][6][7][8] We wish to report here investigations aiming at the introduction of a 2, 3 or 4 pyridyl moiety on various 3-alkoxypyrazoles. As only 3--pyridylboronates have been successfully used with the Lam and Chan approach, we focused here on the use of various halogenated pyridines under the optimized Ullmann-based N-arylation method [9][10][11][12][13][14][15][16][17][18] reported by Cristau and Taillefer. 19,20 Scheme 1 depicts such pyridylation from 3-isopropyloxypyrazole 1 and the three possible bromopyridines 2a-c.…”

Synthesis and Antioxidant Properties of Novel N-Substituted Indole-2-carboxamide and Indole-3-acetamide Derivatives

“…The intermediate N-phenylindole-2-carboxylic acid 1 was prepared by Ullmann condensation [9,10]. In this project bromobenzene was used as the arylating agent and a good yield of N-arylindole-2-carboxylic acids was obtained.…”

Synthesis of N‐Aryl‐2‐substituted Tetrahydrobenzimidazoles via Direct N‐Arylation

“…[7] Traditional strategies for the construction of the N-arylimidazole moiety include the Ullmann coupling reaction [8] and nucleophilic aromatic substitution. [9] Unfortunately, the use of the Ullmann coupling reaction usually leads to difficult purification issues, with concomitant low yields.…”