Imidazo indolizines

The synthesis of 2-azacycl[3.2.2]azine (imidazo[2.1.5-c /]-indolizine), 334, by Paudler et al. <1975JOC1210> (Scheme 97) is apparently the only successful synthesis to date, and is in effect a variant of the Vilsmeier-Haack-Arnold method of Scheme 90. All attempts to synthesize the ring system by cycloadditions to imidazo[l,5- ]pyridine have been unsuccessful. 

Little work has been reported. From studies of proton/deuterium exchange rates, 2-methylpyrrolo[2,l-6]thiazole (478) was estimated to have a pKa of 6.4,394 a value comparable with that of 2-methylindolizine (pKa = 5.9).394 In the same way, the basicity of 3,4-dimethylimidazo-[l,5-a]benzimidazole (468b) (pA = 6.01) resembles that of imidazo-[l,2-a]pyridines (pA = 5.05-5.96).398 It would seem, therefore, that the basicity of azapentalenes parallels that of related indolizine derivatives [Eq. (40)]. 

Several names have been used in the chemical literature for pyrrolo[l,2-a]pyridine including pyrrocoline, pyrindole, pyrrodine and 8-pyrrolopyridine, but the one which is now used by Chemical Abstracts, and which will be used in this chapter, is indolizine. The numbering of the system is shown in formula (1). The denomination of aza derivatives follows the replacement nomenclature system, e.g. 1-azaindolizine, etc. It should be noted that Chemical Abstracts follows the systematic fusion nomenclature 1-azaindolizine, for instance, is imidazo[l,2-a]pyridine. The cyclazine nomenclature is treated in Section 3.08.9.1. 

Ohler, E., El-Badawi, M., and Zbiral, E., Dialkyl (l,2-epoxy-3-oxoalkyl)phosphonates as synthons for heterocyclic carbonyl compounds. Synthesis of acyl-substituted thiazoles, indolizines, imidazo[ 1,2-fii]pyridines and imidazo[l,2-fii]pyrimidines, Chem. Ber., 118, 4099, 1985. 

Amino-imidazo[l,2-fl]pyridines exist as amino tautomers, but are even more unstable than amino-indolizines. 2- and 5-oxo compounds are in the carbonyl tautomeric form and react with phosphoryl chloride yielding chloro compounds. ... 

The traditional ring synthesis of imidazo[l,2-a]pyridines is based on the Chichibabin route to indolizines... 

Imidazo[l,5-fl]pyridine, on reaction with aqueous HNO2 gave 3-(pyridin-2-yl)-l,2,4-oxadiazole. Suggest a mechanism. What product would be obtained by reaction of indolizine with nitrous acid ... 

The electronic absorption spectra of indolizine and various azaderiva-tives, including imidazo[l,2-a]pyrazine, have been rationalized using SCF configuration interaction calculations. The results are in good agreement... 

The synthesis of [2.2.3]cyclazines, aza[2.2.3]cyclazines and their derivatives has also been covered. The attention of the reviewers has been focused on the study of the developments in the synthesis of several benzocyclazines and azacyclazines by the [8 -I- 2] cycloaddition reaction of the dimethyl acetylene dicarboxylate with various types of indolizines. The synthesis of indolizines, imidazo[l, 2-a]pyridines, and related compounds, which are key intermediates for the synthesis of cyclazines, is also described <88H(27)225i>. 

A similar addition reaction has also been reported for indolizine (429), which upon treatment with TADs gives monoadduct 430 [79H(12)787], Similarly, l-acetylimidazo[l,5-o]pyridine (431) gives with both MTAD and PTAD the corresponding Michael-type adducts 432. In contrast, unsubstituted imidazo[l,5-fl]pyridine, an aza analogue of 429, gives with TADs a 2 1 adduct (95JHC1525),... 

The ring synthesis of imidazo[l,2-a]pyridines is based on the Chichibabin route to indolizines (Section 25.1.2), but using 2-aminopyridines instead of 2-alkylpyridines. The initial reaction with the halo-ketone is regioselective for the ring nitrogen, so isomerically pure products are obtained. 2-Oxoimidazo[l,2-a]pyridines are the products when an o-bromo-ester is used instead of a ketone. 

In 4-alkyl(benzyl)-IPs, the methyl and methylene groups possess enhanced chemical reactivity that increases greatly in their monoquaternary salts. The quaterniza-tion of base 304 by a-bromoketones gave salts 314-316 that were converted into imidazo[4,5-g]indolizine 317-319 derivatives when treated by bases. 

The acaricidal effect on bean mite Tetranychus urtical Koch"" of a 0.1% solution of 2-thioanilide 1-MeIcP with respect to Keltan as standard (100%) was 80%, for base 2-(4-OH-3-MeOPh)-IcP and phenacylium salt 1-MeIcP (86SUP993620, 98SUP879945) it was 90%.yi-BrPh-imidazo[4,5-g]indolizine (98SUP879946) showed the same performance as Keltan. 

Two 5-phenacylium salts 2-H- and 2-Ph-lMeIcP exhibited a strong insecticidal effect towards room flies comparable with that of Keltan (86SUP915432). p-BrPh-imidazo[4,5-g]indolizine proved to be effective against rice weevil (98SUP879946). 

Sandeep C, Padmashali B, Kulkami RS. Efficient synthesis of indolizines and new imidazo[l,2-a]pyiidines via the expected cyclization of aromatic cycloimmonium... 

Formation of Complex Heterocycles. The C—H activation of pyridine (generally used in excess amount) has enabled the synthesis of more complex heterocycles such as imidazo and pyrazolo pyridines as well as indolizines. Copper metal salt... 

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