Indolizine, 2-phenyl

Indolizine, hydroxy-conformations, 4, 451 GLC retention times, 4, 451 synthesis, 4, 121 tautomerism, 4, 198, 452 Indolizine, 2-hydroxy-synthesis, 4, 463 Indolizine, 8-hydroxy-conformation, 4, 452 Indolizine, 2-hydroxymethyl-synthesis, 4, 461 Indolizine, 3-hydroxymethyl-synthesis, 4, 461 Indolizine, 6-hydroxymethyl-synthesis, 4, 461 Indolizine, methyl-mass spectra, 4, 187, 450 NM 4, 448 Indolizine, 2-methyl-diazo coupling, 4, 454 mass spectra, 2, 529, 4, 450 nitration, 4, 50, 454 nitrosation, 4, 454 reaction with diaryl disulfide, 4, 460 reaction with nitroethane, 4, 460 Indolizine, 3-methyl-basicity, 4, 454 Indolizine, 5-methyl-acidity, 4, 461 synthesis, 4, 466 Indolizine, 6-methyl-mass spectra, 4, 450 Indolizine, l-methyl-2-phenyl-nitration, 4, 454 nitrosation, 4, 454, 455 Indolizine, 3-methyl-2-phenyl-reaction... 

The reaction of 196 with phenyl chlorocarbene 198 illustrates the synthesis of indolizines by cyclization of pyridinium ylides (Scheme 7). Cyclization of ylide rotamer 199 generates the intermediate product 200, which undergoes elimination of chloride to provide compound 201 <2005EJ01532>. 

Allene-substituted lactams or cyclic imines are useful intermediates in the synthesis of indolizine derivatives. While the former are stable and need a Pd(0) catalyst and the presence of phenyl iodide to react < 1997TL6275>, the latter are produced in situ and react immediately (Scheme 37) <2001JA2074>. 

The lactam 145, bearing a terminal triple bond, is transformed into the corresponding allene derivative 146 through a Crabbe reaction (Equation 7). Using Pd(PPh ()4 as the catalyst and in the presence of phenyl iodide, the corresponding indolizine is obtained. The lactam nitrogen atom is added to the central carbon atom of the allene... 

Nitration of indolizines often runs the risk of oxidation. The orientation of the substitution appears to depend on the experimental conditions nitration of 2-methylindolizine in a mixture of nitric acid and sulfuric acid occurs at the 1 -position (46JCS1075) in acetic anhydride at -70 °C, on the other hand, 2-methyl-3-nitroindolizine is formed (72JCS(P1)2954). The nitration of 2-phenylindolizine with nitric acid in aqueous sulfuric acid gave 2-(4-nitro-phenyl)indolizine (32a) and l-nitro-2-(4-nitrophenyl) indolizine (32b) together with 20% of an unidentified dinitro compound, possibly 3-nitro-2-(4-nitrophenyl)indolizine (32c) <79JCS(P2)312>. 

Treatment of allylpyridinium salts with weak bases gave ylides (152) an intramolecular 1,5-cyclization then yielded dihydroindolizines (153), which are prone to oxidation to (154). More than 90% of (153) is formed if R1 is phenyl and R2 is benzoyl or acetyl. If R is H or p-anisyl the indolizine (154) is the major product. 1,5-Cyclizations of ylides of the type (152) with a different substitution pattern have been investigated. This type of reaction seems to be somewhat unpredictable since the 1,5-cyclization is accompanied by 1,3-dipolar cycloadditions (Section 3.08.6.2.2) to a varying extent (75JCS(Pl)575). 

If R is benzoyl or acetyl and R1 is phenyl, a dihydro product (43) is formed in over 90% yield. If R is H or phenyl, an indolizine (44) is the major product, and the ease of oxidation of 43 appears to depend on the nature of R1. For an electron-donating group such as />-anisyl, the oxidation occurs very rapidly. 

The reaction of indolizine with V.W-dimethylformamide and phosphorus oxychloride gave almost exclusively indolizine-3-aldehyde.166 The Vilsmeier formylation of 6-ethoxycarbonyl-2-methylindolizine gave the 1,3-dialdehyde, but with the corresponding 2-phenyl compound the product was almost totally the 3-aldehyde.167... 

Nitration of indolizines is seldom attempted in view of accompanying oxidation reactions. Thus the synthesis of 6- and 8-nitro-2-phenyl-indolizine has been achieved by the cyclization of appropriately substituted 2-methyl-1-phenacylpyridinium bromide.179 However, 1-nitro and 1,3-dinitro compounds have been prepared.4 From the behavior of the indolizine nucleus toward other electrophiles, 3-nitroindolizine might be expected to be the primary product. This compound has been synthesized using a dilute solution of nitric acid in acetic acid at - 70°C where the substrate could well be the base and not the 3-protonated cation as in a nitric acid-sulfuric acid mixture.180... 

Treatment of 2-benzoylpyridine with DMAD gives mainly trimethyl indolizine-l,2,3-tricarboxylate, whose genesis is explained in the next section, and a 1 1 molar adduct that is considered253 to be formed by a phenyl migration and to have structure 26. The evidence for this structure is quite unconvincing, and other structures such as 27 are more likely. 

Comins, D. L. LaMunyon, D. H. Chen, X. Enantiopure N-acyldihydropyridones as synthetic intermediates asymmetric synthesis of indolizine alkaloids (-J-205A, (-J-207A, and (-J-235B./. Org. Chem. 1997, 62, 8182-8187. Padwa, A. Muller, C. L. Rodriguez, A. Watter-son, S. H. Alkylation reactions of3-(phenyl-sulfonyl) methyl substituted cyclopentanones. Tetrahedron 1998, 54, 9651-9666. 

An electrophilic substitution at the pyrroloid five-membered ring of 5-methyl-2-phenyl-indolizine with ethoxalyl chloride gave a 1,3-disubstituted derivative (2). This was converted into a mixture of the [2.2.3] cyclazine (3) and the [2.3.3]cyclazine (4) by an intramolecular condensation occurring at the activated 5-methyl group of the pyridinoid six-membered ring (see Sections 3.08.2.5 and 3.08.4 for other examples.)... 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

---