2-Pyrrolines

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

The pyrrolines or dihydropyrroles can exist in three isomeric forms 1-pyrroline (3,4-dihyro-2JT-pyrrole [5724-81-2]) (16) is an unstable material that resiniftes upon exposure to air 2-pyrroline (2,3-dihydro-lJT-pyrrole [638-31-3]) (17) is even more unstable only 3-pyrroline (2,5-dihydro-lJT-pyrrole [109-96-6]) (18) is reasonably stable. 3-Pyrroline bods at 91°C and has a density of 0.9097 g/cm and a refractive index of 1.4664. 

Pyrrole can be reduced catalyticaHy to pyrroHdine over a variety of metal catalysts, ie, Pt, Pd, Rh, and Ni. Of these, rhodium on alumina is one of the most active. Less active reducing agents have been used to produce the intermediate 3-pyrroline (36). The 2-pyrrolines are ordinarily obtained by ring-closure reactions. Nonaromatic pyrrolines can be reduced easily with to pyrroHdines. 

Pyrrole oxidizes in air to red or black pigments of uncertain composition. More usehil is the preparation of 2-oxo-A -pyrrolines, which is best carried out by oxidation of the appropriate pyrrole with in pyridine (37), eg, 3,5-dimethyl-ethyl-3-pyrrolin-2-one [4030-24-4] from... 

Catalysts. Silver and silver compounds are widely used in research and industry as catalysts for oxidation, reduction, and polymerization reactions. Silver nitrate has been reported as a catalyst for the preparation of propylene oxide (qv) from propylene (qv) (58), and silver acetate has been reported as being a suitable catalyst for the production of ethylene oxide (qv) from ethylene (qv) (59). The solubiUty of silver perchlorate in organic solvents makes it a possible catalyst for polymerization reactions, such as the production of butyl acrylate polymers in dimethylformamide (60) or the polymerization of methacrylamide (61). Similarly, the solubiUty of silver tetrafiuoroborate in organic solvents has enhanced its use in the synthesis of 3-pyrrolines by the cyclization of aHenic amines (62). 

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). 

Poly(imides) — see 3-Pyrroline-2,5-diones Poly(imidines) — see 3-Pyrrolin-2-ones Polyiodides... 

V-(l-Isopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl)amine Formation/Cleavage ... 

A/-(1 -lsopropyl-4-nitro-2-oxo-3-pyrrolin-3-yl), 577 A/-2,4-Dimethoxybenzyl, 577 A/-2-Azanorbornenyl, 578 A/-2,4-Dinitrophenyl, 578 Quaternary Ammonium Salts, 578 A/-Benzyl, 579... 

A-Acyliminium precursors in tetracarbonyliron-mediated stereoselective alkylations of 5-(R)-isopropoxy-3-pyrrolin-3-ones 98EJ01729. 

Diazonium salt 185 (R = H) when coupled with different CH active compounds yielded 3-hydrazono derivatives (e.g. 186 and 187). Hydrazono derivatives 186 and 187 were cyclized into 3-(l,4-dihydropyridazin-l-yl) 188 and 3-(pyrrolin-l-yl) derivatives 189, respectively (00MI33). 

Rolgamidine (14) is a dihydropyrrole derivative which has antidiarrheal activity It can be synthesized by alkylation of trans 2,5-dimethyl-3 pyrroline (12) with methyl bromoacefate to give 13 An amide-ester exchange reaction with guanidine hydrochloride completes the synthesis of rolgamidine (14) [3]... 

Thermal rearrangement of 2-vinylaziridines yields 3-pyrrolines. When aziri-dines 192 were heated in decalin at 180 °C, 3-pyrrolines 193 were formed in 75-85% yields (Scheme 2.48) [75]. A similar rearrangement was also observed by Lwowski and coworkers [4]. This type of rearrangement can be effectively pro-... 

Scheme 2.49 Palladium(0)-catalyzed isomerization of 2-dienylaziridines to 3-pyrrolines.

Palladium(O)-catalyzed isomerization of 2-dienylaziridines 201 to 3-pyrrolines 202 was reported in 1985 by Oshima, Nozaki, and coworkers (Scheme 2.49) [78]. This isomerization is in striking contrast to Ibuka s palladium-catalyzed isomerization of 2,3-trans-2-vinylaziridines to the corresponding 2,3-cis isomers (see Section 2.4.6) [29]. 

Thermal rearrangement of 2-vinylaziridine 203, with an electron-withdrawing substituent on the nitrogen atom, at reflux in decalin predominantly yielded 2-pyr-roline 204 along with some 3-pyrroline derivatives 205 (Scheme 2.50) [79]. A similar reaction was also observed with l-alkyl-2-phenyl-3-vinylaziridines 206 [80]. From these observations, the nature of the products formed depends on the natures of the substituents on the aziridine ring if the ring carbon carries a phenyl substituent, the thermolysis in most cases preferentially yields 2-pyrrolines. 

Hydrogen shifts are often observed in thermal isomerizations of vinylaziridines. Heating of compounds 221 at 180 °C produced mixture of 3-pyrrolines 222 and hydrazones 223 (Scheme 2.54) [87]. The formation of 223 can be explained in terms either of a concerted hydrogen shift as depicted in 224 or of diradical intermediates 225, both of which would be followed by thermal isomerization of the (Z)-carbon-carbon double bonds to provide the ( ) isomers 223. 

Under the conditions of the Birch reduction, IV-Boc amides such as 60 can be reductively alkylated in high yields, presumably via a dianion intermediate which is protonated by ammonia at C-5 leaving an enolate anion at C-2 <96JOC7664>. Quenching the reaction with alkyl halides or ammonium chloride then affords the 3-pyrrolines 61. 

IH of allenic amines also occurs in the presence of silver salts. IH of a-allenic amines proceeds in good yields in the presence of AgBp4 and provides a useful method for 3-pyrrolines synthesis via Endo-Trig processes (Eq. 4.93) [314]. 

A good example of a concerted cheletropic elimination is the reaction of 3-pyrroline with IV-nitrohydroxylamine, which gives rise the the diazene 21, which then undergoes elimination of nitrogen. 

CsHnNOe 3-/ -D-RibofuranosyI-3-pyrroline-2,5-dione (Showdomycin) SHOMYC 30 457... 

Akiyama developed a novel [3+2] cycloaddition reaction of alkenyl Fischer carbene complexes 11 with simple imines 12 in the presence of a catalytic amount of GaCb to produce 3-alkoxy-2,5-disubstituted-3-pyrroline derivatives 13 <00JA11741>. 

Katritzky developed a facile synthesis of l,2-diaryl(heteroaryl)pyrroles in a two-step procedure from A-allylbenzotriazoles via intramolecular oxidative cyclization in the presence of a Pd(II) catalyst <00JOC8074>. Thus, treating A-allylbenzotriazole (21) with n-butyllithium followed by addition of a diarylimine yielded the (2-benzotriazolyl-l-arylbut-3-en)anilines 22 which were subsequently heated in the presence of the system Pd(OAc)2-PPh3-CUCI2-K2CO3 to undergo intermolecular amination with simultaneous oxidation of the intermediate 3-pyrroline to the pyrroles 23. 

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