1.2- Dimethyl-2-pyrroline

Addition to 1,2-dimethyl- -piperideine or 1,2-dimethyl- -pyrroline is followed by intramolecular alkylation by the ester group as a side reaction to give 140 and 141 ( = 1, 2), respectively. Cyclization products 142 and... 

The /V -hydroxylamino compounds (404) and (405), obtained from the reaction of tert-butyl acetate with 3,4-dihydroisoquinoline-A-oxide or 5,5-dimethyl-pyrroline-/V-oxide, when boiled in methylene chloride in the presence of triphenylphosphine, carbon tetrachloride and triethylamine, are transformed to (1,2,3,4- tetrahydroisoquinolin-l-ilidene) acetate (406) or (pyrrolidin-2-ilidene) acetate (407) (Scheme 2.181) (645). 

The use of nitrone scavengers was precedented by the work of Iwamura and Inamoto (1967), who had used esr spectroscopy to detect the nitroxide formed by addition of cyanopropyl radicals to the cyclic nitrone, 5,5-dimethyl-pyrroline-N-oxide (DMPO) [2], and had actually isolated the cyanopropyl radical adduct of the nitrone [3]. 

These low selectivities were improved by changing the amine substituents of the catalysts 34 from diisopropyl/dicyclohexyl to C2-symmetric 2,5-dimethyl-pyrroline ring, leading to two diastereomeric catalysts 35 (Scheme 6.14), which were synthesized in the same way as catalysts 34 [9]. The catalytic competency of 35 was established using standard phase-transfer alkylation conditions to afford the alkylation product with up to 37% ee. Enantioselectivities obtained using diastereomers of the catalyst 35 were different, but not opposite, which suggests that the stereocenters function cooperatively in one diastereomer, but not in the other. 

Uric acid is present in human plasma at much higher levels than those encountered in other primates because the enzyme urate oxidase is absent from human tissues (Cutler 1984). it has therefor e been proposed that uric acid is an important antioxidant for humans (Ames et al. 1981). Urate reacts with peroxynitrite with an apparent second order rate constant of 4.8 x 10 M s in a complex process, which is accompanied by oxygen consumption and formation of allantoin, alloxan, and urate derived radicals (Santos et al. 1999). The main radical was identified as the aminocarbonyl radical by the electrospray mass spectra of its 5,5-dimethyl-/-pyrroline-N-oxide adduct. Mechanistic studies suggested that urate reacts with peroxynitrous acid and with the radicals generated from its decomposition to form products that can further react with peroxynitrite anion. 

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). 

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... 

The alkylation of imines by an alkyl halide to give an iminium salt will be illustrated by selected reactions over a period of years. A more complete survey is available (88). Decker and Becker (89) prepared a number of iminium salts (91, for example) by mixing methyl iodide and aromatic imines in benzene. 2,5-Dimethyl-2-pyrroline (92) has been alkylated and the... 

Heterocyclic enamines often undergo two-step 1,3 cycloaddition with methyl vinyl ketone. This involves electrophilic attacks by an olefinic carbon and by a carbonyl carbon (24,25). For example, 1,2-dimethyl-Zl -pyrroline (14), when treated with methyl vinyl ketone, produces 1,6-dimethyl-2,3,4,5-tetrahydroindole (15) (24). The requirement which must be met so that this type of cyclization reaction can take place is that the a position of the heterocyclic enamine be carbon substituted. This provides... 

Partial hydrogenation of pyrrole derivatives and partial dehydrogenation of pyrrolidines afford /I -pyrrolines (80-82). However, because of the complex nature of the reaction, it is of little preparative value. The same is true for isomerization of /) -pyrrolines to /) -pyrrolines (83). A photodehydrogenation of 2,6-dimethylpiperidine (26) has been observed recently, affording 2,6-dimethyl-3,4,5,6-tetrahydropyridine (27) in a good yield (84)-... 

Tertiary pyrrolines (49, = 1) and piperideines (49, = 2) (if R = H and the enamine can exist in the monomeric form or if R = aryl) evidently possess an endocyclic -double bond (79,155,156). The stretching frequency of the double bond can be lowered to 1620-1635 cm by conjugation with an aromatic substituent. The double bond of an analogous compound with aliphatic substituents in position 2 may occupy either the endo or the exo position. Lukes and co-workers (157) have shown that the majority of the five-membered-ring compounds, traditionally formulated with the double bond in a position, possess the structure of 2-alkylidene derivatives (50) with an exocyclic double bond, infrared absorption at 1627 cm . Only the 1,2-dimethyl derivative (51) is actually a J -pyrroline, absorbing at 1632 cm . For comparison, l,3,3-trimethyl-2-methylene pyrrolidine (52) with an unambiguous exocyclic double bond has been prepared (54). 

Quaternary ammonium salts of pyrrolines 106) can be prepared only indirectly 197). Addition of bromine to l-dimethylamino-4-pentene followed by removal of hydrogen bromide afforded, depending upon the dehydrohalogenation conditions, quaternary bromides derived from either l,2-dimethyl-/f -pyrroline (107) or l-methyl-2-methylenepyrrolidine (108) (Scheme 7). 

An explanation of the exclusive N methylation of 1,2-dimethyl-J -piperi-deine by means of methyliodide is more difficult. Pyrrolines and piperideines which are not alkylated on the nitrogen atom afford only quaternary ammonium salts on alkylation (203-205), for example 119. 

By means of perbenzoic acid oxidation, a bicyclic oxazirane (233,234) (152) is formed from 5,5-dimethyl-4-phenyl-/l -pyrroline (151). 

Enamines are also reduced with formic acid (247). Distillation of 1,2-dimethyl-.d -pyrroline formate (156) affords 1,2-dimethylpyrrolidine (248). The reaction is usually carried out by heating of the enamine salt with... 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

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

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]... 

In related work, the reactions of hydrogen peroxide with iron(II) complexes, including Feu(edta), were examined.3 Some experiments were carried out with added 5.5"-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent fa so-called spin trap) for HO. These experiments were done to learn whether HO was truly as free as it is when generated photochemically. The hydroxyl radical adduct was indeed detected. but for some (not all) iron complexes evidence was obtained for an additional oxidizing intermediate, presumably an oxo-iron complex. 

Recendy, PEN, a-4-pyridyl-oxide-N-t-butyl nitrone (POEN) or 5-5,dimethyl-1, pyrroline-N-oxide (DMPO) were evaluated in models of experimental shock (endo-toxic, traumatic and mesenteric artery occlusion in rats). All three nitrones, when given prior to the insult intraperitoneally, were protective. When the nitrone s spin trapping ability was inactivated by exposure to solar light and air, they were no longer efficacious (Novelli, 1992). 

FIGU RE 10.1 The structure of DMPO. The diamagnetic compound 5,5-dimethyl-l-pyrroline-iV-oxide reacts with an unstable radical R to form a relatively stable radical adduct. 

Independent work by Schmid93 and by Padwa94 on the photochemistry of 2H-azirines has shown that irradiation of such systems leads in the first instance to the formation of nitrile ylids (nitrilium betaines). Subsequent 1,3-addition to a variety of dipolarophiles affords five-membered heterocycles. These additions take place in a stereospecific and regioselective manner thus, irradiation of the diphenyl-2f/-azirine 117 in the presence of dimethyl maleate leads to the formation of the two isomeric 1-pyrrolines... 

In the context of preparing analogues of chiral l,2-dimethyl-3-(2-naphthyl)-3-hy-droxy-pyrrolidines, which are known non-peptide antinociceptive agents, Collina and coworkers have reported the solvent-free dehydration of hydroxypyrrolidines to pyrrolines under microwave conditions (Scheme 6.141) [278]. In a typical experiment, the substrate was adsorbed onto a large excess of anhydrous ferric(III) chloride on silica gel and then irradiated as a powder under microwave conditions for 30 min at 150 °C. The microwave method leads to dehydration without racemiza-tion and provides higher yields in considerably shorter times than the conventionally heated process. 

The scavenging ability toward O2 can also be measured by using electron spin resonance (ESR) spectrometry. The 02 anion is trapped with 5,5-dimethyl-1-pyrroline TV-oxidc (DMPO), and the resultant DMPO-OH adduct is detected by ESR using manganese oxide as internal standard. Noda and others (1997) used this technique to evaluate antioxidant activities of pomegranate fruit extract and its anthocyanidins (delphinidin, cyanidin, and pelargonidin). 

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