The heterocycle resulting from a named synthesis is shown in brackets, e. The index of named reactions covers the named reactions, reaction types and principles for synthesis of the aforementioned heterocyclic systems. Multiple activation pathways of benzene leading to. Originally, hammett study was based on ionizations of m and pxc 6 h 4 y, where log kk 0 was introduced as the hammett equation. Pdf benzene is a ubiquitous environmental pollutant that is known to cause hematotoxicity and leukemia in humans. Due to the larger number of units, the number of possible valence isomers is also greater and at least 21. Benzene oxide is known to exist in equilibrium with its tautomeric valence structure, the oxepin1aa. Both alternatives of nelectron delocalization have been discussed in con nection with measured properties of cht l, azp i, and oxp 3. The presence of both oxepin and benzene oxide isomer was observed by low temperature. This observation was taken as evidence for the initial formation of the corresponding equilibrating valence tautomeric arene oxideoxepine intermediates 22. The left shift, which is observed in favor of 1 h over 2 h, appears in contrast to the reported right shifted equilibria including.
The oxepinarene oxide intermediates formed during metabolism undergo. Examination of the valence tautomers benzene oxide and oxepin and two derivative systems by ab. Valence tautomerism is studied in the co iihs sq 2 bpyco iiils sqcatbpy mononuclear cobalt complex by using dft methods hs, high spin. A pair of valence tautomers with formula c6h6o are benzene oxide and oxepin. The arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions s n 2 which are characteristic of simple epoxides. Albumin adducts of benzene oxide and 1,4benzoquinone as.
The enthalpies of the valence tautomerism between benzene oxide 3 and oxepin 4. Concise synthesis of the plant growth regulator theobroxide. Mitsutaka kudoh, susumu sudoh, shigeyoshi katagiri, tomoo nakazawa, mariko ishihara, mamoru jinguji, miwako higashi, hiroyuki yamaguchi, ryuta miyatake, yoshikazu sugihara and chizuko kabuto, xray structures and dipole moments of tropones annulated with furan, benzene, and oxepin, bulletin of the chemical society of japan, 79, 8, 1240, 2006. In synthetic porphyrin systems, valence tautomerism has been. A related dimethyl derivative exists mainly as the oxepin isomer, an orange liquid. Pdf identification of benzene oxide as a product of. Journal of the american chemical society 2015, 7 45, 1448114487. Attempts have been made to assess the degree of electron delocahzation. Examination of the valence tautomers benzene oxide and oxepin. Pyrylium 3 oxide and 4,5epoxy2cyclopentenone valence tautomerism. The oxepin benzene oxide equilibrium is affected by the ring substituents. Tautomerism chemistry britannica encyclopedia britannica. Substituent effects on tautomerization of oxepine to. A rapid total racemization of the substituted benzene 2,3oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations.
These metrics are regularly updated to reflect usage leading up to the last few days. Although it is the benzene oxide valence tautomer that is attacked by nucleophiles and rearranges to phenols in acidic media, it is the oxepin valence isomers that suffer oneelectron oxidation. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. Synthesis and chemistry of syn2hydroxyindane 3a,7aoxide. Benzene oxide exists in dynamic equilibrium with its valence isomer. In order to find substituent effects on tautomerization of benzene oxide to oxepine, hammett study via ab initio is employed in this manuscript. Applications to the benzene oxide oxepin valence tautomerization and to glycine conformation are presented. Tautomers are structural isomers constitutional isomers of chemical compounds that readily.
Exploration of selected pathways for metabolic oxidative. The very rapid benzene oxide oxepin equilibrium plays an important role in the metabolism of benzene by cytochrome p450. A computational molecular orbital study of the oxide and. Highvalent manganeseoxo valence tautomers and the influence. A gradientpreserving algorithm for removing outlying charge has been implemented. Journal of molecular structure theochem, 234 1991 227246 227 elsevier science publishers b. A rapid total racemization of the substituted benzene 2,3oxides was found to have occurred, via their oxepine valence tautomers, in accord with. A molecular orbital study of the benzene oxideoxepin valence. Structure energetics and reactivity in chemistry series search series, vol 3. Theoretical determination of molecular structure and. The mechanism of action of doxepin is presumable linked to the effect on the.
Chemoenzymatic synthesis of monocyclic arene oxides and. Stark a and rastetter w 1996 structureactivity relationships in the mutagenicity and cytotoxicity of putative metabolites and related analogs of benzene derived from the valence tautomers benzene oxide and oxepin, environmental and molecular mutagenesis, 10. Identification of benzene oxide as a product of benzene metabolism by mouse. Examination of the valence tautomers benzene oxide and oxepin and two derivative systems by ab initio methods. Albumin adducts of benzene oxide boalb and 1,4benzoquinone 1,4bqalb were investigated among 4 workers exposed to benzene and 51 unexposed controls in tianjin, china. The enthalpies of the valence tautomerism between benzene oxide 3 and oxepin 4 and of benzene sulfide 5 and thiepin 6 are estimated from posthartree. Therefore, valence tautomerizations involving the second row elements b, c, n. How steric effects favor thiepins over their benzene. Theoretical study of the mechanism of valence tautomerism. Several selfconsistent fieldcosmo coupling schemes were examined in an attempt to reduce computational effort. Concentrations of both adducts increased with benzene exposure range 0. Theoretical studies of the benzene oxideoxepin valence. Oxepine derivative an overview sciencedirect topics.
Oxepin is an oxygencontaining heterocycle consisting of a sevenmembered ring with three double bonds. Benzene oxide and the potential 8electron system oxepin exist in valence. In reality oxepin benzene oxide 7 is resistant to attack by hard nucleophiles such as oh. We have calculated the geometry and energy of the valence tautomers benzene oxide and oxepin using the semiempirical am1 model and the 631g and 631g basis sets utilizing full geometry optimization. Dehydration of these diols, which is driven by rearomatization, gives phenol and 1naphthol. In recent years these substances have become of intense in terest as potential intermediates in the metabolism of. The calculated enthalpy for this valence tautomeric equilibrium differs from that reported by vogel et al in 1967, but agree well with the value calculated by kollman using the mindo3 method. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Pyrylium 3oxide and 4,5epoxy2cyclopentenone valence. This compound exists mainly as oxepin at room temperature, even if. For the dimethyl analog of the benzene oxideoxepin system 9 and 10 the.
The parent c 6 h 6 o exists as an equilibrium mixture with benzene oxide. A molecular orbital study of the benzene oxideoxepin. Benzene oxide 1a and indan8,9 oxide 1b were examined as symmetrical arene oxide substrates schemes 1 and 2. Enantiopure cisdihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. Introduction, history, and recent developments enol k f kr keto 1. How steric effects favor thiepins over their benzene sulfide tautomers at theoretical levels article in journal of molecular structure theochem 861. Calculations at the b3lyp level of theory reproduce well the energy gap between the co iihs and co iiils forms giving an energy gap of 4. The hydration is catalyzed by epoxide hydrolase enzymes. Nmr spectroscopic measurements show that the equilibrium is rapidly established activation energies of the forward and reverse reactions 9. Read investigation of benzene oxide in bone marrow and other tissues of f344 rats following metabolism of benzene in vitro and in vivo, chemicobiological interactions on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at. A pair of valence tautomers with formula c 6 h 6 o are benzene oxide and oxepin. Bock department of chemistry, philadelphia college of textiles and science, philadelphia, pa 19144 u. Tautomerism, the existence of two or more chemical compounds that are capable of facile interconversion, in many cases merely exchanging a hydrogen atom. Synthese eines oxepins vogel 1964 angewandte chemie.
Valence tautomers are of fundamental interest because of their distinct optical. Benzene oxide and naphthalene1,2 oxide hydrate to give dihydroxydihydrobenzene and 1,2dihydroxydihydronaphthalene, respectively. Enzymecatalysed synthesis and reactions of benzene oxide. The valence isomers are not restricted to isomers of benzene.
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