4- Amino-3-pyrrolin-2-ones

LeBerre and Renault have utilized 2-amino-1-pyrroline (30) in condensation reactions with a,/3-unsaturated carbonyl derivatives and -di-carbonyl compounds to prepare a wide variety of partially saturated pyrrolol 1,2-aIpyrimidines in which the pyrrole portion of the molecule is always completely saturated. For example, condensation of the amino-pyrroline (30) with substituted maionic esters (29) affords13,14 2-hydroxy-4,6,7,8-tetrahydropyrrolo[l,2-a]pyrimidin-4-one (31a). Spectral data indicate the betaine form (31b) to be preferred [Eq. (5)]. 

Pyridazin-3(2H)-ones rearrange to l-amino-3-pyrrolin-2-ones (29) and (30) upon irradiation in neutral methanol (Scheme 10), while photolysis of 5-amino-4-chloro-2-phenylpyridazin-3(2H)-one gives the intermediate (31) which cyclizes readily to the bis-pyridazinopyrazine derivative (32 Scheme 11). 

Photoreaction of l-vinyl-4-alkyl-5-aminotriazolines leads to unexpected pyrrolines and pyrroles.459 The 1-vinylaziridine formed by ring closure of the 1,3-diradical undergoes a selective ring cleavage at one of the C—N bonds (bearing the amino group) followed by cyclization with the j -vinyl carbon to give the products (Scheme 157)459... 

One type of compound generated by pyrolysis of simple peptides consists of small molecules similar to those obtained from the pyrolysis of component amino acids such as hydrocarbons (aromatic hydrocarbons from peptides containing Phe orTyr), aldehydes, pyrrole, pyrroline, indole (from peptides containing TRP), some aliphatic amines, etc. 

Besides, in view of the ascertained knowledge of the stability of simpler systems of this type, the imine structure should be the preferred one (128, 129). In line with this evidence is the finding of Cerny and Sorm (98), who demonstrated that the elimination of the hydrochloric acid from the chloramine corresponding to JV-demethylconanine led to the 20(A )-pyrroline (see Section II,G). Thus, the double bond in conkurchine could not be in the 17,20- or 20,21-positions. Jarreau et al. (74a, 75,130) ruled out the 20(A)-position by the synthesis of 3 -methyl-amino-A-demethylcona-5,20(V)-diene and 3 -aminodemethylcona-5,(20)iV-diene which are not identical with conessidine and conkurchine, respectively. 

FIGURE 14.28 The vinylogous relationship between the carbonyl and the amino group in pyrroline-3-ones gives them the reactivity of secondary amidesd ... 

Pyrroline-3-ones were used as peptidic bond surrogates by Hirsehmann et al. In sueh compounds (Figure 14.28), thanks to vinylogy, the earbonyl and the amino group show the same chemieal reaetivity to that of a secondary amide. 

The Eschenmoser reaction was applied a second time as one of the methods to introduce the -butyl appendage. The alkylated a-amino ester (97) was oxidized to the monosubstituted thiolactam (98), and introduction of the butyl side chain, via sulfide contraction as described above, yielded a mixture of vinylogous carbamates (99). Treatment of the carbamates (99) under transfer hydrogenolysis conditions yielded the optically pure dialkylpyrroline (100), another component of the ant trail pheromone. Subsequent reduction of the pyrroline with platinum afforded the optically pure ds-2,5-dialkyl-substituted pyrrolidine (101). Other pyrrolidine-containing alkaloids have been prepared by similar approaches involving the Eschenmoser reaction. ... 

Ring contraction occurs also on irradiation of pyridazine-3(2//)-ones to give a mixture of pyrrolines 278 and 279 (minor product).576 Similarly, 3-methyl-l-phenyl-hexahydropyridazine-6-one gives 280.577 However, photolysis of 5-amino-4-chloro-2-phenylpyridazine-3(2H)-one, a selective herbicide, in sunlight gives a mixture of 281 and 282, the last compound originating from 281.578 The first photoisomerization of 3-hydroxypyrid-azinium betaines into pyrimidinones converts 283 into 284 the mechanism proposed involves valence isomerization.579... 

This methodology was used as the key eyclization step in the stereo- and enan-tioselective synthesis of ( + )- and (-)-a-kainic acid 43, the prototype of a group of neuroexeitatory amino aeids that are important substrates in physiological and pharmacological studies of the central nervous system [22e-f], One of the major obstacles in the synthesis of kainic aeid is the establishment of the 3,4-c/5-stereochemistry. This was overcome by using on the pyrroline intermediate 42 a... 

Machol n (159) has incubated 2-hydroxyputrescine in the presence of o-aminobenzaldehyde in phosphate buffer at pH 6.5-7 with purified diamine oxidase and obtained a 1,2-dihydroquinazolinium compound (Scheme 8). Only one product was formed, although, since there are two amino groups in the substrate molecule, two reaction products would have been expected. Apparently, however, there is a preferential formation of the 4-hydroxy-A -pyrroline (160), which is converted spontaneously into pyrrole if no o-aminobenzaldehyde is present. 

Startg. azlactone refluxed 2 hrs. with K-malononitrile in ter -butanol 1-benzoyl-2-amino-3-cyano-5-cinnamylidene-Z 2-pyrrolin-4-one. Y 88%. F. e., also isolation of the intermediate, s. H.-D. Stachel and K. K. Harigel, Ardi. Pharm. 302, 654 (1969). 

Spin adducts with 5,5-dimethyl-1-pyrroline-A-oxide (DMPO) have been identified for the first time from the pulse radiolysis of a range of mono- and di-carboxylic acids and one amino acid. The spin adducts showed small proton hyperfine coupling constants around 0.7-1.7 G. The nitrogen and C2-proton hyperfine coupling constants were determined to be smaller and the g factors larger than those of DMPO-alkyl radical adducts. 

In the similar iodocyclization of a-amino ynones 41 (Scheme 24), PEG MOO was a less effective solvent and better yields of 42 were obtained at room temperature with acetonitrile as a solvent [47]. However, the a-amino ynones 41 underwent 5-endo-dig cycloisomerization in PEG 3400 rmder microwave irradiation in the presence of platinmn(ll) chloride affording pyrrolin-3-ones 43 [48]. In the presence of potassium carbonate, the reaction proceeded without substantial epimerization of the products 43. The recyclability of tiie catalytic system and PEG 3400 was also investigated. 

Synthetic interest in 3-pyrrolin-2-ones arises from their occurrence in nature, diverse biological activity, and utihty as building blocks for the preparation of nitrogen heterocycles and y-amino acid derivatives. This review systematically (based on bond connections) describes de novo syntheses of... 

Anary-Abbasinejad and coworkers reported an interesting three-component type ace cyclization leading to substituted 3-pyrrolin-2-ones that combined an amidation ( a bond), Michael addition ( e bond), and intramolecular Wittig reaction ( e bond) (Scheme 103 2010SC1350). Treatment of 2-amino-4-methylpyridine 391, DMAD (303), and ethyl chlorooxoace-tate (392) with triphenylphosphine gives the 3-pyrrolin-2-one 394 via the ylide intermediate 393. 

Nair and coworkers have used a type bde multicomponent reaction sequence to prepare N-amino-3-pyrrolin-2-ones (2001CL738, 2002T8113). 

Heating an aromatic aldehyde (e.g., 420), DMAD (303), and the N-amino-isocyanide 421 gives N-amino-3-pyrrolin-2-ones (e.g., 422) (Scheme 111). Presumably, this is another example of a multicomponent reaction leading to a 2-aminofuran intermediate, which is converted to a 3-pyrtolin-2-one via a Dimroth rearrangement. 

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