Pyrrole with singlet oxygen

Tertiary enamines are oxidized to different compounds. 7V-Methyl-pyrrol gives 92% of /V-methylsuccinimide by oxidation with peroxybenzoic acid in chloroform at room temperature [311]. A -Cyclohexenylmorpholine, with singlet oxygen, is oxidized to cyclohexanedione (equation 524) [42], The oxidation of Af-phenylacetylenyl-lV,Af-diethylamine yields the M diethylamide of phenylglyoxylic acid (equation 525) [7S6]. 

Oxidative decarboxylation of pyrrole-2-carboxylic acids Reaction of pyrrolc-2-carboxylic acids such as 1 and 2 with singlet oxygen in i-PrOH or CH3CN and water (3 1) results in 5-hydroxy-3-pyrrolin-2-ones in high yield. 

The reaction of 1,2-dihydropyrrolizines with singlet oxygen proceeds as expected for pyrroles <85AP(318)663>, as shown in Equation (2). 

Thiophenes. It has been reported that thiophenes, unlike the furans and pyrroles, do not react by sensitized photooxidation however, when thiophene is substituted with alkyl group, it does undergo reaction with singlet oxygen (Matsuura and Saito, 1976). Photosensitized oxidation of 2,5-dimethylthiophene in either chloroform or methanol gives a diketone and a sulfme as shown in Scheme 21 (Skold and Schlessinger, 1970). Three possible pathways which lead to sulfine formation have been proposed (Scheme 21). 

The reaction mechanism for the aerobic oxidation of the pz to seco-pz can be attributed to a formal 2 + 2 cycloaddition of singlet oxygen to one of the pyrrole rings, followed by cleavage (retro 2 + 2) of the dioxetane intermediate to produce the corresponding seco-pz (160). This mechanism is shown in Scheme 29 for an unsymmetrical bis(dimethylamino)pz. Further photophysical studies show that the full reaction mechanism of the photoperoxidation involves attack on the reactant by singlet oxygen that has been sensitized by the triplet state of the product, 159. As a consequence, the kinetics of the process is shown to be autocatalytic where the reactant is removed at a rate that increases with the amount of product formed. 

It was suggested27-288 that all these compounds would be generated from the unstable endoperoxide (20) (originated from a Diels-Alder reaction of singlet oxygen with the dienio pyrrole system) through various paths, as indicated in Scheme I. 

A process that has proved valnable in synthesis is the addition of singlet oxygen to A-alkyl- and especially A-acyl-pyrroles ° prodncing 2,3-dioxa-7-aza-bicyclo[2.2.1]heptanes, which react with nncleophiles, such as silyl enol ethers, mediated by tin(II) chloride, generating 2-substitnted-pyrroles that can be nsed, as the example shows, for the synthesis of indoles via intramolecular electrophilic attack by the carbonyl group at the pyrrole P-position. 

The thiazine (42) can be photo-oxidized in the presence of methylene blue. The major photo product (50) is derived via a singlet oxygen ene reaction <88JPR(330)79). Thiazines such as (42) are relatively stable to heat, but (42) can be thermally degraded at 180°C with copper bronze to yield the pyrrole (51) (Scheme 10) <92MI 606-01). 

Pyrroles are very sensitive to the action of singlet oxygen ( O2). Wasserman (1970) has observed a novel type of oxidation in the case of aryl-substituted pyrroles exemplified by the photooxidation of 2,3,4,5-tetraphenylpyrrole in methanol. There is special interest in the reactions of imidazoles with O2 since it has been shown that photooxi-dative inactivation of certain enzymes involves destruction of histidine residues, and more specifically oxidation of the imidazole ring (Wasserman and Lenz). These heterocyclic system behave in many respects like furans and pyrroles, but are more prone to cleavage through reactions resembling the oxidation of enamines by 02 (Wasserman et al. 1968). 

Singlet oxygen reacted stereospecifically with 2-vinyl-thiophens in a 1,4-cycloaddition to give thermally stable 1,4-endoperoxides (147). The previously discovered [2 + 2] photoaddition of benzophenone to 2,5-dimethylthiophen to give oxetans has been extended to other carbonyl derivatives. Mechanisms explaining the formation of pyrroles, obtained by u.v. irradiation of a number of thiophens in the presence of propylamine, have been discussed. Irradiation of (148) led to the Dewar thiophen (149). The structures of dimerization products and Diels-Alder adducts with furans were elucidated. ... 

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