Imidazo heterocycles

Guchhait and Madaan (2010) reported a novel microwave-assisted one-pot novel tandem de-tert-butylation of tert-butyl amine in an Ugi-type multicomponent reaction product. Tert-butyl isocyanide has been explored as a useful convertible isonitrile for the first time affording access to molecular diversity of pharmaceutically important polycyclic N-fused imidazo-heterocycles. 

The formal derivation of the analogs, described in the foregoing, represents, from the point of view of systematic organic chemistry, a shift to the derivatives of other heterocyclic systems. In the case of pyrimidine aza analogs we arc dealing with derivatives of symmetrical or asymmetrical triazine in the case of purine aza analogs, the derivatives produced are those of imidazo[4,5]-i -triazine and z -triazolo [4,5-d] pyrimidine. 

The hydrolysis proceeds via a diazafulvene intermediate, which in these systems can be formed without a total loss of aromatic character of the tricycle. It is tempting to suggest that, using this reasoning, linearly annelated 2-trifluoromethyl-imidazo[4,5-g]quinoline should be inert toward alkaline hydrolysis, as formation of the diazafulvene intermediate will again involve total dearomatization of the heterocyclic system (Scheme 36). 

The association of the excited state derived from four 2-substituted imidazo [4,5-/]quinolines with 2-propanol in cyclohexane has been studied. The unusual bathochromic shift and the bandwidth of the fluorescence spectra of these heterocyclic compounds in 2-propanol-cyclohexane solutions, compared with those... 

Paudler and Helmick515 have measured half-lives for deuteration of some heterocycles by deuterated sulphuric acid at 100 °C. The equivalent first-order rate coefficients (lO ) are as follows imidazo[l, 2-a]pyridine, 427(3-H) imidazo[l,2-a]pyridine-N-methiodide, 62(3-H) imidazo[l,2-a]pyrimidine, 123-(3-H) imidazo[l,2-a]pyrimidine-N-methiodide, < 6.4 (3-H, 5-H) 1,2,4-tri-azolo [1,5-a]pyridimidine, 128(5-H) 1,2,4-triazolo [1,5-a]pyrimidine-N-methiodide, 11.7 (5-H). The lower reactivity in each case of the corresponding methiodides shows that the bases react as such and not as the conjugate acids. 

Kinetic studies of base-catalysed hydrogen exchange of heterocyclic compounds have been carried out. Paudler and Helmick515 measured second-order rate coefficients for deuteration of derivatives of imidazo[l,2-a]pyridine(XXXIII), imidazo[l,2-a]pyrimidine(XXXIV), and 1,2,4-triazolo[1,5-a]pyrimidine(XXXV)... 

Scheme 8 Microwave-assisted synthesis of imidazo-annulated heterocycles...

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

At the origin of this abundance of publications on iV-heterocyclic carbenes is the structural ligand diversity now available (Fig. 1.2). This developing area is noteworthy as most early developments were mainly focused on imidazolylidene and imidazo-lidinylidene NHC-types. 

The UV-spectra of azolides have already been discussed in the context of hydrolysis kinetics in Chapter 1. Specific infrared absorptions of azolides were mentioned there as well increased reactivity of azolides in nucleophilic reactions involving the carbonyl group is paralleled by a marked shift in the infrared absorption of the corresponding carbonyl bond toward shorter wavelength. For example, for the highly reactive N-acetyl-tetrazole this absorption is found in a frequency range (1780 cm-1) that is very unusual for amides obviously the effect is due to electron attraction by the heterocyclic sys-tem.[40] As mentioned previously in the context of hydrolysis kinetics of both imidazo-... 

A ten Jt electron heterocycle, imidazo [7,2-a] Pyridine was studied by Paudler and Blewitt 115>. The protonation occurred at Ni, which was calculated to have a total n electron density less than N4 (Fig. 

Almost accidentally, Bienayme and Bouzid discovered that heterocyclic amidines 9-76 as 2-amino-pyridines and 2-amino-pyrimidines can participate in an acid-catalyzed three-component reachon with aldehydes and isocyanides, providing 3-amino-imidazo[l,2-a]pyridines as well as the corresponding pyrimidines and related compounds 9-78 (Scheme 9.15) [55]. In this reachon, electron-rich or -poor (hetero)aromatic and even sterically hindered aliphatic aldehydes can be used with good results. A reasonable rahonale for the formation of 9-78 involves a non-con-certed [4+1] cycloaddition between the isocyanide and the intermediate iminium ion 9-77, followed by a [1,3] hydride shift. 

Reaction of pyrido[ 1,2- pyrazin-4-one 304 with methyl cyanoacetate, cyanamide, and JI-oxo nitriles in AcOH at 70 °C gave imidazo[ l,2- ] pyridine 331, imidazo[l,2- ]-pyrimidine 332, and tetracyclic heterocycles 333, respectively <1996JHC639>. 

Nucleophilic substitution of a halogeno-heterocycle is the key step in the synthesis of imidazo-, oxazolo-, thiazolo-, and benzothiazolopyridopyrimidines 255 and 256 <2000T5185> and 257. Intramolecular iV-acylation is the final cyclization step leading to the thiazolino compound 258 (Scheme 63) <1995AF306>. 

Scheme 6.48 Synthesis of imidazo[l, 2-a]annulated N-heterocycles via the Ugi reaction.

Recent studies have demonstrated the synthetic potential of 5-aminoim-idazoles (96) as intermediates for heterocyclic synthesis, particularly for the synthesis of bicyclic systems, including imidazo[4,5-6]pyridines... 

Diazadienes have been used in organic synthesis for the preparation of various heterocyclic compounds. Alkylation of 1,3-diazadienes 207 and the benz-fused analog 210 at the nitrogen atom by aryl acyl bromides provided the iV-alkyl amidinium bromides 208 and 211, which underwent annulation to the 2,3-dihydro-imidazo[2,l-A]thiazole 209 and imidazo[2,l- ]benzothiazoles 212, respectively (Equations 92 and 93) <2001S741, 2002J(P1)741>. 

With a-A3-iodanyl ketone precursors. Exposure of (2-acetoxyvinyl)phenyl-A3-iodanes 369 to 2-imidazolidinethione and triethylamine in methanol produced the bridgehead heterocycle 370 of type 5,6-dihydro-imidazo[2,l-3]thiazoles (Equation 166) <2003JOC7887>. 

With chlorinated quinones. New heterocycles containing 1,2-dihydro-imidazo [l,2- ]imidazol-3-one 405 or 1/7-imi-dazo[l,2- ]pyrazole moieties were obtained via charge-transfer interaction of creatinine or 3-aminopyrazole with some 7i-deficient compounds such as 2,3-dichloro-5,6-dicyano-l,4-benzoquinone, 2,3,5,6-tetrachloro-l,4-benzoquinone, 2,3-dichloro- or 2,3-dicyano-1,4-naphthoquinone, and 3,4,5,6-tetrachloro-l,2-benzoquinone (Equation 183) C1996BSB159, 2001HC0541, 2000PS1>. 

A new heterocyclic system, 3 ,4-dihydro-3//-benzo[4,5]imidazo[l,2-f]oxazol-l-one 462, was synthesized by reaction of 4,4-dimethyl-5-methylene-l,3-dioxolan-2-one with o-phenylenediamine in the presence of copper bromide as catalyst in carbone dioxide at 60-80 °C under high pressure (Equation 217) <1999CHC216>. 

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