4- Butyl-3-pyrrolin-2-ones

Ethoxypyrrolin-5-one l-Pyrrolin-5-one, 2-ethoxy- (8) 2H-Pyrrol-2-one, 5-ethoxy-3,4-dihydro- (9) (29473-56-1) tert-Butyl N-(l-ethoxycyclopropyl)carbamate Cyclopropanecar-bamic acid, 1-ethoxy-, tert-butyl ester (8) Carbamic acid, (1-ethoxycyclopropyl)-, 1,1-dimethylethyl ester (9) (28750-48-3 41879-49-6)... 

Irradiation of a ferf-butyl alcohol solution of 2-ethoxy-pyrroline-5-one (12) with Vycor filtered light from a 450-W mercury lamp results in formation of ferf-butyl N-(ethoxycyclopropyl) carbamate (13) in 73% isolated yield17,18 When the irradiation is conducted in the non-hydroxylic solvent, tetrahydrofuran, 1-ethoxycyclo-propyl isocyanate (20) can be isolated in 78% yield. Both 13 and 20 can be prepared in synthetically useful quantities. 

Complex 9 and [CpFe(o-BPXCO)CH 2C1 ] [o-BP = tri(o-biphenyl)-phosphite] were also prepared by the reaction of HC1 with [CpFe(L)-(CO)CH2OEt] (L = PPh3, o-BP) (47). Alkylation of the two complexes with sodium /crt-butyl acetoacetate and pyrroline cyclohexanone enamine yielded six of the eight possible alkylation products. The two products where L was o-BP and the nucleophile was tort-butyl acetoacetate did not form, presumably because of excessive steric hindrance. The excess of one diastereomer over the other ranged from 10 to 64%. 

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. ... 

Addition of thiols in basic solution to the C=C—C=0 bond system in a,/3 imsaturated ketones, such as 4-benqrlidene-l-buQrl-pyrrolidine-2,3-dione, has been observed, forming with benzenethiol in piperidine, l-butyl-3-hydroxy-4(a-phenylthiobenzyl)-3-pyrrolin-2-one . Addition of thiols primarily to the C=C bond in C=C—C=0 systems in quinones and lactones has been observed . The reactions were studied in neutral or alkaline solution and probably involve attack by the thiolate anion. In compounds containing both carbonyl or carboxyl groups and acetylenic triple bonds, addition occurs primarily across the acetylene bond. Cyclization of the initial product so formed is also observed . ... 

Incubation of rat embryonic mesencephalic tissue, rich in dopaminergic neurones, with 0.2 mM tert-butyl hydroperoxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide for 20 min resulted in the trapping of radicals (Karlsson et al. 2000). The main radicals detected in cell suspensions were the tert-butoxyl radical and the methyl radical, indicating the one-electron reduction of the peroxide followed by a P-scission reaction. The appearance of electron paramagnetic resonance signals from the trapped radicals preceded the onset of cytotoxicity, which was almost exclusively necrotic in nature. The inclusion of resveratrol (3,5,4 -trihydroxy-fra s-stilbene) in incubations resulted in the marked protection of cells from ferf-butyl hydroperoxide. 

The compounds (Z)-3-hexenal, methanethiol, (Z)-l,5-octadien-3-one, dimethyltrisulfide, 3-iso-propyl-2-methoxypyrazine and 3-5 c-butyl-2-methoxypyrazine contribute to the aroma of the fresh vegetable. In cooked spinach, (Z)-3-hexenal decreases and dimethylsulfide, methanethiol, methional and 2-acetyl-1-pyrroline are dominant. 

The reaction of NSBV 6-la with terf-butyl isocyanide (f-BuNC) in toluene was first monitored by NMR spectra. No reaction took place even when the reaction mixture was heated to 120 °C for 12 h in a sealed tube. However, in the presence of a catalytic amount of zinc triflate (5 mol%), reaction of the above mixture proceeded smoothly at room temperature. The reaction was very clean and finished within 2 h, affording the 5,8-diaza-4,8-brexadiene derivative 6-12a as a tetracyclic triimine in 93 % isolated yield (Scheme 6.2). No formation of the C-N bond insertion product 6-11 was detected. Single-crystal X-ray structural analysis of 6-12a revealed a cage-shaped skeleton containing a cyclopentanimine core fused with one cyclohexane ring and two pyrroline rings (Fig. 6.6). 

Finally, a 5-endo radical cyclization approach to 5-alkylidene-3-pyrrolin-2-ones has been reported by Tang and Li (Scheme 53 2004OL3229). Treatment of 4-iodo-3-octenoamide 227 (R = Ph) with t-butyl hypochlorite gives 5-(butyhdene)-3-pyrrolin-2-one 228 the same reaction with the corresponding primary amide 227 (R = H) gives the iminoketone 229. 

Quai and coworkers utilized a [4+1] cycloaddition with isocyanide to prepare highly substituted 3-pyrroHn-2-ones (Scheme 60 2004TL1413). Treatment of benzylidene-1,3-diketone 243 with tert-butyl isocyanide (244) gives 5-hydroxy-3-pyrrolin-2-ones 246 (Scheme 24). The authors propose an oxidative rearrangement mechanism for the conversion of initial adduct 245 to the observed product 246. Similar reactions have been reported by others in the synthesis of 3-aryl-4-carboethoxy-5-hydroxy-3-pyrrolin-2-ones (2007T8987) and 3,5-diaryl-5-hydroxy-3-pyrrolin-2-ones (2007TL8056). 

Finally, in an investigation of Passerini-like reaction products, Basso and coworkers reported a type de synthetic approach to 3-hydroxy-3-pyrro-lin-2-ones (Scheme 96 20090L4068). The Passerini-like reaction between two equivalents of phenylacetic acid (371) and butyl isocyanide (372) under microwave irradiation gives the amide 373. Treatment of 373 with base then gives the 3-hydroxy-3-pyrrolin-2-one 375 via intermediate 374. 

Acid-mediated hydrolysis of 5-halopyrrole-2-carboxylates provides access to 5-carboxy-3-pyrrolin-2-ones, but this transformation often lacks the regioselectivity of other methods. This reaction was first reported by Siedel (1943LAC144). In a more recent example, Battersby and coworkers have treated 5-bromopyrrole-2-carboxylate 548 with sulfuric add in methanol, and a mixture of 3-pyrrolin-2-ones 549 and 550 was obtained in low yield (Scheme 156 1988PT(1)1557). These reaction conditions led to both hydrolysis of the bromine and deprotection of the <-butyl ester followed by decarboxylation. In a related reaction involving a symmetrical substrate, Lugtenberg and de Groot converted 5-bromo-2-trichloroacetyl-3,4-dime-thylpyrrole into 3,4-dimethyl-3-pyrrolin-2-one via treatment with NaOH (1982MI2). 

Pereira and colleagues found that isobutylamine and highly substituted 5-alkylidene-furan-2-ones in methylene chloride at 0 °C provided N-iso-butyl-3-pyrrolin-2-ones (2014EJMC127). Some of these products inhibited... 

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