Pyrrolines and Pyrrolidines

Oppolzer, R. Achini, E. Pfenninger, and H. P. Weber, Helv. Cliitn. Acta., 1976, 59, 1186. Gy. Prater, Tetrahedron Letters, 1976, 4517. 

Dicarboxylic acid imides e.g. (189) were prepared in high yield by cyclization of carboxylic acid amides (190) with trifluoroacetic acid this technique avoided dehydration to the nitrile (191), which was easily achieved with acetic anhydride. This work is part of a total synthesis of maleimycin.  

Ring contraction of the tetrahydro-l,3-diazepine-2,4,5-trione (197) in boiling decalin took place with elimination of phenyl isocyanate this method represents the conversion of a 2,3-dihydrofuran-2,3-dione (196) into a 2,3-dihydropyrrole-2,3-dione (198) thermolysis in the absence of solvent led to the quinoline (199). The zwitterionic 2,4-dioxopyrrolidine (200) was obtained in moderate yield by the condensation of o-(a-hydroxycinnamoyl)benzoic acid with tripiperidinomethane in ether-DMF at room temperature.  

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Pyrrole and its derivatives have been extensively studied. General references include Jones and Bean (77MI1), Boyer (86MI1), and Schofield (67MI1). However, there are few reports of nitrations of pyrrolines and pyrrolidines. 

Beilina, F. and Rossi, R. (2006) Synthesis and biological activity of pyrrole, pyrroline and pyrrolidine derivatives with two aryl groups on adjacent positions. Tetrahedron, 62, 7213-7256. 

R. Huisgen, Pyrrolines and pyrrolidines (tetrahydropyrroles), preparation by 1,3-dipolar addition. Proc. Chem. Soc. (London) pp. 357-370 (1961). 

Pyrroline is a desirable starting material for alkylation of heterocycles. 1-(Methoxycarbonyl)-3-pyrroline2 has been used to prepare 2,5-dialkylated pyrrolines,3 which resulted in the synthesis of the Pharaoh ant trail pheromone43 and gephyrotoxin 2 2 3.4b Alkylation of 3-pyrrolines has also led to the synthesis of 12-azaprostaglandins.5 The submitters have used a formamidine derived from 3-pyrroline to provide access to 2-substituted pyrrolines and pyrrolidines,6 which has led to the synthesis of the unnatural (+)-anisomycin.7... 

Figure 2. Some naturally-occurring polyhydroxylated pyrroline and pyrrolidine alkaloids.

K. Tatatsuki, T. Hattori, T. Kaizu, M. Okamoto, Y. Yokato, K. Nakamura and H. Kayakiri. Antiretroviral pyrroline and pyrrolidine sulfonic acid derivatives. 1990. European Patent Application EP O 407 701 A2. 

The reduction in acid solution of di- and tetrahydropyridazines and pyridazinones is often best understood when their resemblance to hydrazones is considered. The reduction of such compounds has been discussed (Chapter 11), and the primary step is a hydro-genolysis of the nitrogen-nitrogen bond. The reduction of 1,4-dihydro-1-methyl-5-r-butyl-3,6-diphenylpyridazine to pyrroles has been described [148, 149] at more negative potentials, pyrrolines and pyrrolidines may be obtained from pyridazines,... 

Osowska-Pacewicka, K., Zwierzak, A. Reactions of N-phosphorylated aziridines with dianions derived from ethyl acetoacetate and 1,3-diketones new route to substituted pyrrolines and pyrrolidines. Synth. Commun. 1998, 28,1127-1137. 

Chemistry and biology of pyrroline and pyrrolidine nitroxides 05JHC437. 

A -heterocyclic compounds other than pyrazines such as pyrrolines, pyrrrolidines, piperidines and pyrroles are also very important flavor compounds. The formation of pyrrolines and pyrrolidines are reported to be generated from the reaction of proline with glucose (Shigematsu et aL, 1975 Tressl et aL, 1985a). The pyrrolidines possess smoky and roasty aromas while 2-acetyl-1-pyrroline was reported by Tressl et al. (1985b) to have a cracker-like odor. The pyrrole rings from proline and hydroxyproline are present in many of their reaction products. N-acetylpyrrole exhibits a cookie-like and mushroom-like odor (Tressl et ai, 1986). 

N>Condensed heterocyclics from co chloronitriles and diols via l>pyrrolines and pyrrolidines Selective reduction of azomethines... 

Five-membered Rings.— The occurrence of pyrroles, pyrrolines, and pyrrolidines is widespread throughout the field of natural products, and they are also useful precursors to many other interesting ring systems. Hence, the large number of new synthetic methods and modifications of existing molecules precludes a detailed discussion of them all. A few examples will illustrate the general trend this year. 

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