Ring opening Compounds

Mechanistic studies (6,26,27,67) have shown that the acyl enzyme species is the ring opened compound (13), which can tautomerize to the transientiy inhibited amino acrylate (14), and both of these species can react further to give irreversibly inactivated enzyme. Three inactivated forms of the enzyme have been detected. Two, according to labeling studies, retain the complete clavulanate skeleton and the other retains only the carbon chain of the P-lactam ring. Stmcture (15) has been suggested as one possible inactivated form. 

Phosphorylations of diaziridine nitrogen are also possible without ring opening. Compounds (132) (67JMC101) and (133) (80ZOB1502) were prepared using POCI3 and (R0)2P(0)C1 in presence of triethylamine. 

In other cases, attempts to cyclize the hydrazone proved more difficult and resulted in mixtures of compounds. The products obtained along with pyrazol-3-ones were ring-opened compounds or other pyrazole derivatives. Pilgram, who obtained hydrazones 56a,b by standard methodology, reported one such example. 

Some experiments were conducted to determine the influence of the solution pH. The catalytic oxidation of p-coumaric acid has been performed by increasing the initial pH from 3.5 to 7.5 and 11. Although the cleavage of the exocyclic double bond may be pH sensitive we obtained the same major intermediates which are the hydroxybenzaldehyde and the p-hydroxybenzoic acid molecules. The rate of oxidation of these aromatic compounds to ring opening compounds was higher when the initial pH was basic and yielded higher concentrations of maleic and fumaric acids. 

As with its hydrolytic, lactone ring-opening, compound 4 reacts106,107 rather slowly with methanol, with formation of an equilibrium mixture containing methyl D-glucopyranuronate (62) and 4 in the ratio of 3 1. Compound 62 is formed much more rapidly and in high yield, however, on treatment27,108 of 4 with methanol in the... 

Barbitone (barbital, 282) was irradiated in aqueous solution at pH 10 with light of 254 nm wavelength to give the ureide (289) in 68% yield. In ethanol, the derivative (290) was formed (62%). With A-methylbarbitone (283) in buffer at pH 10, a mixture of the ureide (291) and the imidazole (292) was obtained. It was suggested that the ring-opened compounds were formed via isocyanates (288). Reaction with water would then give an acid which would spontaneously decarboxylate, but in ethanol a stable urethane (290) would form [173]. 

Imipenem (5.46) has not completely fulfilled such expectations [122], Indeed, this compound is unstable in both acidic and alkaline media. In weakly acidic solutions, imipenem undergoes complex oligomerization, a reaction initiated by the intermolecular attack of the carboxy group on the /3-lactam Fig. 5.17) and yields, finally, a diketopiperazine compound. In weakly alkaline solution, an intermolecular reaction between the /3-lactam and (iminome-thyl)amino group was observed Fig. 5.18). This reaction proceeds via an unstable dimer that breaks down to thienamycin (5.45) and a /3-lactam ring-opened compound bearing a Ai-formyl group [123],... 

The main human plasma metabolite of chlormezanone (5.75), a muscle relaxant, was found to be the ring-opened compound 5.76. Since hydrolysis... 

Major oxidation products of propanolol and metoprolol formed during ozonation in aqueous solution were investigated by Benner et al. [102, 103]. In the case of propanolol, the main ozonation product is a ring-opened compound with two aldehyde moieties, which results from ozone attack to the naphthalene ring [103]. Formation of aldehyde moieties was also one of the main oxidation routes during metoprolol ozonation, together with hydroxylation [102]. 

The data in Table II.ll show that the participation of the Sn(ANRORC) mechanism decreases with decreasing potassium amide/substrate ratio. When no potassium amide is present, the participation of the ANRORC mechanism is zero and the aminolysis occurs according to the Sn(AE) mechanism. Apparently in the amination of the highly 77-electron-deficient 1,3,5-triazines, a competition is involved between the strong nucleophilic amide ion, which leads via a-adduct 136 and the ring-opened compound 137 to product 2-[ N-amino]-4,6-diphenyl-l,3,5-triazine, and the weaker nucleophile liquid ammonia, which replaces by an Sn(AE) process the... 

Hydrazination of 4-aryl-3,5-dioxo-2,3,4,5-tetrahydro-l,2,4-triazine (66) also affords a rearranged product, 4-amino-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine (81JHC953). This replacement of the A-aryl group by the N-amino group requires the intermediacy of the ring-opened compound 67. This intermediate could be isolated under mild conditions and its structure was proven by an independent synthesis. From this structure it can be concluded unequivocally that the ring transformation involves initial addition of the hydrazine at C-5 and not at C-3 (Scheme III.37). 

The robust nature of the rhodium-iodide catalyst is also revealed in reactions with ortho-halo phenols that proved to be problematic with the first-generation catalyst system (Section 9.3.1). By employing the [Rh(PPF-P Bu2)I] catalyst, complete conversion is obtained with 2-bromophenol to give 6 in 94% yield, and with 95% enantiomeric excess after only 1.5 h of reaction time at 1 mol% catalyst loading (Scheme 9.3) [11]. The ready availability of these ring-opened compounds has been utilized to prepare enan-tiomerically enriched benzofurans 7. 

The use of trimethyltin chloride in place of the tributyltin derivative leads predominantly to the formation of a ring opened compound. Jutzi, P. Gilge, U. J. Organomet. Chem. 1983, 246, 159. 

When ethoxymethylenemalononitrile and ethyl ethoxymethylenecyanoac-etate were used in boiling ethanol or in 1,2-ethylene glycol at 100°C, the primarily formed ethyl 8-substituted 9-amino-l 1-oxo-l 17/-pyrido[2,l -6]-quinazoline-6-carboxylates (307) gave ring-opened compounds (308) (89JHC161). 

Reaction of 230 with ethyl chloroformate gave a mixture of ring-opened compounds that could be reduced with lithium aluminum hydride or catalytically (Scheme 30) the latter method provides a secondary amine (231) as the major product. 

With a large excess of lithium aluminum hydride, the major product was 231, but the unsaturated ring-opened compounds could not be obtained in a pure state. Thus the trichloroethylcarbamate method would appear to be the one of choice. 

Attempts to prepare 7-keto-compounds from the bases (138) and (139) by the action of manganese dioxide and titanium chloride gave the ring-opened compounds (140) and (141).167... 

Lycoperdic acid (30), as well as its ring-opened compound H02C(CH2)2C(0H)-(C02H)CH2CH(NH3)C02, have been isolated from this common forest mushroom.31... 

The reaction of an azepinium ion (3), generated in situ, with a number of aromatic substrates (benzene, anisole, phenol, furan and thiophene) usually gave aryl-2//-azepines [e.g. (4) from benzene] as the major products.7 In the case of reaction with pyrrole, however, a ring-opened compound (5) was the major product. Some condensed thiophenes have been shown8 to give products of substitution at C(l). For example, (6a) gave (6b) on diazo coupling. 

The NMR data showed that the reaction was very clean when phosphoric acid was present. Essentially a single product was formed. The product did not contain carbonyl functionality. The spectrum, however, was not that of glutaminol (the expected ring opened compound) but rather of prolinol (see Fig. 5). The minor peaks in the spectrum corresponded to a small amount of unreacted pyroglutaminol. Conversely, when acid was not added, the resultant solution contained a complex mixture of products. 

With a,P unsaturated ketones the expected cyclopropanes could not be isolated, but acrylonitrile derivatives can also be used as acceptor olefins 40). They provide cyanocyclopropanes in good yield (entries 6, 7), which might be interesting precursors for other cyclopropanes or ring opened compounds because of the synthetic versatility of the nitrile group. 

Reactions of trimethylsilyl enol ethers with diazo ketones give cyclopropanes contaminated by ring opened compounds 60,61). Use of the more stable tert-BuMe2Si-derivatives or of Rh2 (0Ac)4 as a catalyst might eventually improve the situation. O-Silylated ketene acetals and O.S-ketene acetals, respectively, did not provide products with cyclopropane structure 61 ... 

Treatment of tetrahydroberberine with ethyl chloroformate gives the ring-opened compound (41 R = C02Et, R2 = CH2C1), which can be hydrolysed to the base (41 R1 = H, R2 = CH2OH) cyclization of this with formaldehyde gives demethoxymecambridine (42).130... 

Attempted catalytic hydrogenation of oxime E,Z-25 ended up with significant amounts of ring-opened compounds hampering distillative purification of the desired compound rac-26. 

The metabolism of benzene to ring-opened compounds (e.g., muconic acid) may be pertinent to the development of a biomarker of benzene exposure and effect (Ducos et al. 1990, 1992 Inoue et al. 1989 Lee et al. 1993 Melikian et al. 1993 Ong and Lee 1994 Witz et al. 1990). However, the dose-response curve for metabolism of benzene to urinary muconic acid in humans needs to be determined. If urinary... 

Cyclodextrins (/ -CDs) are very useful in creating microenvironments in which aziridines can be opened using mild conditions. The reaction of aziridines such as 83 with / -CD and sulfur nucleophiles such as thiocyanate <2005SL489> or thiophenols <2005TL6437> provides a mild route to ring-opened compounds 84 and 85 (Scheme 23). 

The deamination of the bornylamines by various methods has been examined including the use of nitrous acid in acetic acid. ° Whereas ring-opened compounds are obtained to some extent from endo-bornylamine, practically none are obtained from the exo-isomer. This work should be taken in conjunction with an earlier paper dealing with the same reaction in water, conditions which lead to less camphene and more hydroxylated compounds with both endo- and exo-bornylamines. It is claimed that the camphor obtained in the deamination of 2-exo-hydroxy-3-exo-aminobornane with nitrous acid is formed via a 2,3-endo-endo hydrogen shift. 

Conversion of (— )-)3-pinene to (— )-oc-pinene is said to occur in better chemical yield and good optical yield when refluxed with 15 mole % benzoic acid for 48 h. The mechanism of the rearrangement of the pinenes with acid has been discussed again by Williams and Whittaker, who postulate the existence of two interconvertible carbonium ions (272) and (273), which can either revert to a-pinene or react further, the one (272) leading to the fenchane skeleton and the other to the bornane skeleton, camphene, or ring-opened compounds. Using... 

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