5-Hydroxy-2//-pyrrol-2-ones

SCHEME 13.49 Proposed mechanism for the formation of 5-hydroxy-2//-pyrrol-2-ones 202 by Quai et al. [86]. 

Dibenzo[Z),e ]thiepinones are reductively ring opened at the benzylic C-S bond [194] anthrone and anthraquinone are among the products. The cleavage and ring closure are akin to those observed in the reduction of 2-phenyl-l,3-thiazin-6-ones to 3-hydroxy-pyrroles [195]. 

A, 15) and 6-[ [l-[5-amino-5-arboxypentyl]-3- hydroxy-pyrrol-2-yl]-(E)-2-methylidene-5-methyl-l,2H-pyrrol-3-one-l-ly]-2-amino-hexanoic acid (dilysyldipyrrolone B, 6) They were novel pyrrolyl-methylidene-pyrrolone derivatives containing two lysine residues, which were named dilysyldipyrrolones A and B.14). Contributions of these compounds to a heated solution were estimated by the color dilution method. Dilysyldipyrrolones A and B contributed to about 5% and 10% of total color, respectively, while 4-hydroxy-5>methyl-2-furfurylidne 3(2H)-furanone contributed only to 0.05%. 

Pyridazinones may undergo ring contraction to pyrroles, pyrazoles and indoles, the process being induced either by an acid or base. The structure of the final product is strongly dependent on the reaction conditions. For example, 4,5-dichloro-l-phenylpyridazin-6(lFT)-one rearranges thermally to 4-chloro-l-phenylpyrazole-5-carboxylic acid (12S), while in aqueous base the corresponding 4-hydroxy acid (126) is formed (Scheme 40). 

Complex reactions occur on the autoxidation of pyrroles (see Section 3.05.1.4) predictably, susceptibility to autoxidation increases with increasing alkyl substitution, llie photosensitized reaction of pyrrole and oxygen yields 5-hydroxy-A -pyrrolin-2-one, probably by way of an intermediate cyclic peroxide (Scheme 28) (76JA802). 

The importance of ring size holds also for tautomerism of -pyrrol-5-ones and. d -dihydro-6-pyridones. While the former compounds behave as cyclic 1-methyl-2-alkyl-2-hydroxy-5-pyrrolidones 179) (76) [or, on distillation, as the dehydrated l-methyl-2-alkyl-J -pyrrolones (77)], the latter compounds exist as acyclic N-methylamides of 8-oxo-acids (78) [as shown by infrared spectroscopy (/80)j. The dehydration of 78 during distillation to form l-methyl-2-alkyl-. -dihydro-6-pyridones (79) is achieved only with difficulty. 

The ligand group can be introduced either on the meso or on the /5-pyrrole position of the porphyrin ring, but the synthesis of the meso-functionalized derivatives is easier and has been more widely exploited. Balch (50-53) reported that the insertion of trivalent ions such as Fe(III) (32) and Mn(III) (33) into octaethyl porphyrins functionalized at one meso position with a hydroxy group (oxophlorins) leads to the formation of a dimeric head-to-tail complex in solution (Fig. 11a) (50,51). An X-ray crystal structure was obtained for the analogous In(III) complex (34), and this confirmed the head-to-tail geometry that the authors inferred for the other dimers in solution (53) (Fig. lib). The dimers are stable in chloroform but open on addition of protic acids or pyridine (52). The Fe(III) octaethyloxophlorin dimer (52) is easily oxidized by silver salts. The one-electron oxidation is more favorable than for the corresponding monomer or p-oxo dimer, presumably because of the close interaction of the 7r-systems in the self-assembled dimer. 

Nicht nur Pyrrole, 3-Amino-a-p5n one und 3-Hydroxyp Tidone, sondem auch a-P5Tidone selbst sind aus den Addukten von Butadien-carbon-saure-Derivaten zuganglich die Reduktion dieser Addukte mit Zink in Eisessig liefert bei 50—60°C durch Cyclisierung der intermediar auftre-tenden l-Aminobuten-(2)-ole-(4) 3-Hydroxy-3.6-dihydro-p5ridone-(2). 

The photosensitized reaction of pyrrole and oxygen yields 5-hydroxy-A3-pyrrolin-2-one, probably by way of an intermediate cyclic peroxide (Scheme 45) (76JA802). 

The C-2 and C-3 hydroxy derivatives of pyrrole are special in the sense that the tautomeric equilibria favor the pyrrolinone structures (see Section 3.04.6.2). Furthermore, the general synthetic methods are not usually applicable so that we will call attention in this section not only to the methods of directly introducing these substituents, which are rare, but also to those ring construction processes which specifically give the pyrrolinones and indolinones. The indole derivatives have widely used trivial names, oxindole (5) for indolin-2-one and indoxyl (6) for indolin-3-one, Carbocyclic hydroxy substituents in indole and carbazole, on the other hand, for the most part act as normal aromatic phenolic groups. These compounds are usually prepared by application of the standard ring syntheses. 

Three l-hydroxy-3-phenylpyrroles (46) were formed (72JOC1561) in 26-44% yields, instead of the anticipated 6//-oxazines, when the corresponding E-oximes (44) were treated successively with one equivalent of sodium hydride in dimethylformamide (DMF) followed by triphenylvinylphosphonium bromide Z-benzil oxime gave no pyrrole. The cyclization probably proceeds via cyclization to the N-oxide 45 and tautomerism to the 1-hydroxypyrrole. 

Triphenyl- 1,2,4-butanetrione oxime in chloroform with hydrogen chloride cyclized in 70-75% yield to the purple 2,4,5-triphenyl-3f/-pyrrol-3-one 1-oxide (61) (30JA1590), along with an isoxazoline derivative. The pyrrlone was reduced by lithium aluminum hydride in ether [76JCS(P 1)2259] to l-hydroxy-2,3,5-triphenylpyrrole 62. 

Pyralomicins lc and 2c (36 and 38) have been isolated from culture broth of Microtetraspora spiralis as novel antibiotics including antitumor activities. Structurally, 36 and 38 are endowed with the 5-hydroxy-8-methyl- [1]-benzopyrano[2,3-b]pyrrol-4-(l//)-one structure 32 as a common core binding a carba sugar and a sugar moiety, respectively. 

A maltol-ammonia browning reaction produced thirteen pyrazines, two pyrroles, two oxazoles, and one pyridine (12). The major products of this system were 2-ethyl-3-hydroxy-6-methylpyridine and 2-ethyl-3,6-dimethylpyrazine. It is difficult to construct possible formation mechanisms for these compounds from maltol and ammonia. All the carbon atoms must come from maltol. It is possible, then, that maltol degrades into smaller carbon units and that these fragments recombine to form larger carbon units, producing these compounds. Recently, the formation of thiophenones and thiophenes from the reaction of 2,5-dimethyl-4-hydroxy-3(2H)-furanone and cysteine or cystine was reported (13. 14). All these reaction mixtures were reported to possess a cooked meat-like flavor. 

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