A1-Pyrrolines

Comparative studies indicate that abstraction of hydrogen atoms from the methyl group of 1-methylpyrrole is easier than from the methyl group of toluene. Subsequent dimerization and polymerization of the 1-pyrrolylmethyl radicals, initiated by the addition of r-butoxy radicals, occurs and low yields (0.5%) of l,2-bis(l-pyrrolyl)ethane and l-methyl-3-(l-pyrrolylmethyl)pyrrole have been isolated from the tars (B-77MI30500). The radical dimerization of pyrrole initiated with r-butoxy radicals produces 2-(2-pyrrolyl)-A1-pyrroline (B-77MI30500). 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A1-pyrroline (74) in quantitative yield (77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

A fourth possibility is the generation of H202 via oxidation of putrescine (butane-1,4-diamine 2.56). This reaction is catalyzed by copper amine oxidase (E.C. 1.4.3.6). Copper amine oxidases are homodimers in which each unit contains a copper ion and a 1,3,5-trihydroxyphenylalanine quinine co-factor. In plants copper amine oxidases generally oxidize putrescine to 4-aminobutanal (2.57). This latter compound undergoes spontaneous cyclization to A1 pyrroline (2.58), ammonia, and H202, as shown in Figure 2-12 (Medda et al., 1995). 

Oxaloacetate + Glutamate Glutamate + NH3 Glutamate + NAD+ + H20 Succinate semialdehyde + Glutamate Pyruvate + Glutamate A1-Pyrroline 5-carboxylic acid... 

A series of electron deficient alkenes have been reacted with thioimidate methylide under these conditions. Corresponding A1 -pyrrolines are obtained in moderate to high yields.457... 

A,-(Trimethylsilylmethyl)thioureas are readily accessible via the addition of an amine to the corresponding isothiocyanate. They are good starting materials for preparing 2-amino-A1-pyrroline derivatives via their corresponding azomethine ylids. This is illustrated by condensation with maleimide and different alkenes.245,469... 

A. Pyrimine (L-5(2-pyridyl)-2-amino-5-ketopentanoic acid l-2(2-pyridyl)-A1-pyrroline-5-carboxylic acid 119)... 

An inspection of the IR spectra of the condensation products derived from 4-phenyl-2-ethoxy-A1 -pyrroline with diethyl aminomalonate indicates that the hydroxyimidazole (25a) predominates (82JHC193). 

The reaction of 4-phenyl-2-ethoxy-A1-pyrroline (162) with sodium azide in glacial acetic acid at 60 °C gave 6-phenyI-6,7-dihydro-5H-pyrrolo[l,2-a]tetrazoIe (163) (82JHC193). 

N-methylen-tert-butylamin-N-oxid 7991a> and 5,5-dime thyl-A1 -pyrrolin-N-oxid T892 have been employed as spin traps, but a variety of other nitrones is also suitable93. While ESR data from adducts to 81 c give relatively little information on fine structure of the radicals88, in the spectra of adducts from 79 and 78 more such information is recognizable926 d 94 ... 

The same rearrangement was observed somewhat later by the irradiation of 5,5-dimethyl-A1-pyrroline oxide (13). 18 The product (11% yield) was shown to be identical with the oxazirane (14) synthesized from S -dimethyl-A pyrroline and hydrogen peroxide. 

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