Indolizine acetylation

Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

Tnfluoromethanesulfenyl chlonde reacts with the indolizine nng to introduce tnfluoromethylsulfenyl groups at both positions 1 and 3 An acetyl group atposition 3 can be replaced by a trifluoromethanesulfenyl group, whereas the 3-benzoyl and 3 nitroso substituents are unaffected [/] (equation 1) (Table 1)... 

Acetyl-indolizin liefert mit Lithiumalanat 3-Athyl-indoIizin12,vgLa- 11 ... 

Acylation of the highly reactive indolizines may be achieved at the 3-position and, less easily, at the 1-position using acid chlorides, anhydrides and even esters (48CRV(42)6ll). 3-Acetylation of indolizine, 1,3-diacetylation of indole and 2,5-diacetylation of pyrrole have been effected with acetic anhydride at 140-200 °C (see Section 3.02.2.4.8 for details). The indolizines (49) and (50) are formed with ethyl chloroformate and ethyl benzoylacetate respectively. 

Little work has been carried out on halogenation of indolizines. Only the preparation of iodo derivatives appears to be straightforward (71MI30800). Thus iodination of the 3-position of l-acetyl-2-methylindolizine was achieved by treatment with iodine and sodium acetate (69YZ1020). 

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 position of the equilibrium of Eq. (13) depends markedly on the nature of R. When R = H the product is entirely the ketone, whereas when R = CH3 the product can be shown from IR and NMR spectroscopic data to be completely enolized. Whichever form predominates, Schotten-Baumann benzoylation gives the indolizine / -nitrobenzoate ester (67). Acetic anhydride instead of perchloric acid with 65 gives the 1-acetamidoindolizine which is also available from the 1-acetyl compound via the Schmidt reaction. 

An interesting intramolecular cyclization takes place when 1,3-di-(2-pyridyl)-propane-l,3-diol is treated with sodium acetate in refluxing acetic acid.93 l-Acetyl-3-(2-pyridyl)indolizine is formed in 30% yield. Support for the proposed mechanism, shown in Scheme 14, is the observed increase in yield when the reaction is subjected to UV irradiation, which would be expected to increase the proportion of the ds-olefin present. 

The Vilsmeier reaction has been applied to indolizines to yield a variety of products. The normal reaction conditions with jV,jV-dimethyl-formamide and phosphorus oxychloride can give the indolizine-1-aldehyde,168 e.g., with 6-ethyl-2,3-dimethylindolizine. However, N,N-dimethylacetamide with 5-methyl-2-phenylindolizine gave a mixture of isomers, 105 and 106, with the former predominating.165 Hydrolysis of 105 gave enamine 107 instead of the acetyl compound. 

Most of the amines could be acetylated at nitrogen and, under refluxing conditions, at the 1-position. Other routes to acetamidoindoli-zines are from the corresponding acetyl compounds via the Schmidt reaction,79-180 from pyridines via Tschitschibabin reactions, and from acetolysis of an azomethine79 such as 124, which may be derived from the reaction of an indolizine and diphenylformamidine.186... 

Various indolizines containing vinyl groups in the pyridine ring have been synthesized by standard procedures, e.g., Ref. 212. Turchinovich and co-workers found that whereas 2-methyl-6-vinyl- and 1,2-dimethyl-6-vinylindolizine would not polymerize, even in the presence of an initiator, 3-acetyl-l,2-dimethyl-6-vinylindolizine polymerized spon-... 

Nitration of 3-acetyl-2-phenylindolizine using nitric acid in sulfuric acid gives a mixture of 3-acetyl-2-(4-nitrophenyl), 3-acetyl-l-nitro-2-(4-nitrophenyl), 3-nitro-2-(4-nitrophenyl), and l,3-dinitro-2-(4-nitrophenyl) indolizine (Fig. 4) (46JCS1077). 

Pyrrolo[l,2-ci]quinoline is a benzo derivative of indolizine and its 2,7-dimethyl derivative (8.65) is nitrosated, acetylated. diazo coupled, and formylated in the expected 1-position in 90, 40, 90, and 70% yields, respectively (79JHC393). Nitration also goes in the 1-position if the conditions are not strongly acidic, in which case it goes in the 6-position. This... 

Zur selektiven bzw. gleichzeitigen Hydrierung des Indolizin-Geriistes neben Phenyl-und neben Acetyl-Gruppen vgl. z. B. Lit.11 6. 

Shigematsu H., Shibata S., Kurata T., Kato H. and Fujimaki M. (1975) 5-Acetyl-2,3-dihydro-l//-pyrrolizines and 5,6,7,8-tetrahydro-indolizin-8-ones, odor constituents formed on heating L-proline with D-glucose. J. Agric. Food Chem. 23, 233-7. 

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