1.4- Dioxen

Dioxenes react, as expected, to produce thermally unstable dihalocyclo-propanes in high yield [51, 89]. Upon heating, the bicyclic system rearranges to yield the dichloromethyl-1,4-dioxene, whereas the tricyclic system, derived from the benzo-l,4-dioxene undergoes ring expansion to produce the benzo-1,5-dioxepin (Scheme 7.11). 

Most partially saturated ring systems, 2,3-dihydro-l,4-dioxin 10 (sometimes named as 1,4-dioxene), 2,3-dihydro-1,4-dithiin 11, 2,3-dihydro-l,4-oxathiin 12, 2,3-dihydro-l,4-benzodioxin or 1,4-benzodioxane 13, 2,3-dihydro-l,4-benzodithiin 14, and 2,3-dihydro-l,4-benzoxathiin 15 are well investigated. Ring numbering for compounds 10-12 is followed as shown, independently of the presence of substituents. 

The potential energy barrier of 1,4-benzodioxan 13 to ring inversion is 1-2 kcal moP lower than that of 1,4-dioxene 10, typically 6.9 and 8.7 kcalmoP (HF/6-31G ) and 7.5 and 8.8kcalmoP (B3LYP/6-31G ), respectively <1998MI173>. 

A Claisen rearrangement of the 1,4-dioxene 69 provided the pyran 70 asymmetrically (Equation 10) <1998JA12702>. 

Synthesis of 2,3-dihydro-l,4-dithiin 11 was accomplished from l,3-dithiol-2-one 247 in the presence of dibro-moethane and potassium hydroxide <1998JOG3952>, while reaction of 2,3-dichloro-l,4-dioxane with powdered Zn in hexamethylphosphoramide (HMPA) was used for the synthesis of 1,4-dioxene 10 <1998JPP10067773>. To obtain substituted 1,4-oxathianes, the hydrogenation of the corresponding partially saturated compounds has been employed <2001J(P1)2604>. 

Treatment of 23-disubstituted 1,4-dioxenes with a catalytic amount of camphotsulfonic acid in dichloiomethane at room temperature afforded substituted furans <99TL2S21>. 

A 100-ml autoclave was charged with ethyl acetate (24 parts), 1,4-dioxene (20 parts), and t-bu ty 1 pcrox pi val ate (0.3 parts) and then treated with chlorotrifluoroethylene (31 parts) and polymerized at 55°C for 13 hours. The precipitated polymer was isolated and dissolved in 150 ml of tetrahydrofuran (THF) and then precipitated in methanol, the process being repeated twice. Thirty-five grams of product were isolated having a Tg of 154°C and an Mn of28,000 Da with a refractive index of 1.459. The material was soluble in most organic solvents and formed transparent films. 

Dioxene derivatives used in the step 1 copolymerization process. 

Copolymers containing 1,4-dioxene derivatives are illustrated below. 

Heterocyclic polymers containing the 1,4-dioxane ring have been mentioned only briefly in the literature. Cationic addition polymerization of 1,4-dioxene (151) produces polymer (152 Scheme 48) which, along with other poly(l,2-dialkoxyethylenes), is reported to form polymeric complexes with poly(methacrylic acid) (79MI11109). 

The photoinduced 1,4-cycloaddition of alkenes to phenanthra-quinone to give substituted 1,4-dioxenes [Eq. (86)] in good yield was first observed in 1944.824 The addition has since then been more fully investigated, and is applicable to a variety of o-quinones and aromatic... 

The study of this cycloaddition and its mechanism is complicated by the formation in small yield of additional photoproducts. Irradiation of phenanthraquinone (308) in, for example, 2-methylpropene affords the oxetane (309), arising by 1,2-cycloaddition of the alkene to the carbonyl, in addition to the expected 1,4-dioxene (310).334 Oxetanes are the principal products of photoaddition of phenanthraquinone to benzofuran, furano[3,2-y]coumarin, and isocoumarin.329 A further product has the structure (311), and is undoubtedly the... 

Stefan, M. and Bolton, J., Mechanism of the degradation of 1,4-dioxene in dilute aqueous solution using the UV/hydrogen peroxide process, Environ. Sci. Technol., 32(11), 1588-1595, 1998. 

Atkins et al. [130] reported in 1977 that irradiation of mixtures of benzene and methyl acrylate or methyl methacrylate, both acceptors, yields mixtures of endo and exo adducts. A subsequent report from the same groups [120] describes the results of the irradiations of benzene in the presence of ethyl vinyl ether, //-butyl vinyl ether, 2,3-dihydropyran, and 1,4-dioxene. In all these cases, the major products were exo-ortho photocycloadducts. The orientations of these vinyl ethers with respect to benzene, in their loose ground-state associations, were inferred from NMR spectra. For ethyl vinyl ether, n-butyl vinyl ether, 2,3-dihydropyran, and 1,4-dioxene, the vinyl proton resonances were either unaffected by a solvent change from carbon tetrachloride to hexadeuterobenzene or appeared 4-10 Flz downfield, whereas the methyl and/or methylene signals all moved up-field by 10-25 Hz. This implies an endo arrangement of the molecules in the ground state. Thus, the ortho photocycloadducts of vinyl ethers with benzene show exo stereochemistry, even when the ground-state orientation is endo. 

In 1977, Scharf and Mattay [123] found that benzene undergoes ortho as well as meta photocycloaddition with 2,2-dimethyl-1,3-dioxole and, subsequently, Leismann et al. [179,180] reported that they had observed exciplex fluorescence from solutions in acetonitrile of benzene with 2,2-dimethyl-l,3-dioxole, 2-methyl-l,3-dioxole, 1,3-dioxole, 1,4-dioxene, and (Z)-2,2,7,7-tetram-ethyl-3,6-dioxa-2,7-disilaoct-4-ene. The wavelength of maximum emission was around 390 nm. In cyclohexane, no exciplex emission could be detected. No obvious correlation could be found among the ionization potentials of the alkenes, the Stern-Volmer constants of quenching of benzene fluorescence, and the fluorescence emission energies of the exciplexes. Therefore, the observed exciplexes were characterized as weak exciplexes with dipole-dipole rather than charge-transfer stabilization. Such exciplexes have been designated as mixed excimers by Weller [181],... 

The alkenes, which give emitting exciplexes with benzene, quench its fluorescence at nearly diffusion-controlled rates. For 1,4-dioxene, 2,2-dimethyl-... 

The 1,3-dioxoles and 1,4-dioxene are the only alkenes with which exciplex formation and decay can be studied in conjunction with photoaddition. The dioxoles give ortho as well as meta photocycloadducts with benzene [13,14,122], Mattay et al. [15,134,183] have pictured the exciplex as a common precursor to both types. The exciplex is supposed to possess charge-transfer character, from the dioxole to the arene. Formation of the ortho adduct is thought to proceed stepwise as shown in Scheme 36 for anisole and 1,3-dioxole... 

For photocycloaddition, to benzene the following conclusions were drawn from this empirical correlation [124], Olefins with poor electron-donor or poor electron-acceptor abilities yield mainly meta adducts with benzene (i.e., if AG > 1.4-1.6 eV, all other olefins yield mainly ortho adducts). Even ethene, which had seemed to behave exceptionally, fits into this correlation provided that it acts as the acceptor. The transition area from ortho to meta cycloaddition (i.e., the AG region where ortho meta = 1 1) is relatively large ( 0.2 eV). This is considered not to be surprising because the AG correlation is based on many different types of olefins. When only AG values for derivatives of 1,3-dioxole and for 1,4-dioxene were used, the transition area was narrowed to 0.03 eV. Not only ethene but also vinylene carbonate now fit into the correlation. According to the ionization potential rule, this compound should give only ortho photocycloaddition with benzene. Mattay s empirical rule predicts mainly meta addition, which is indeed found experimentally. 

The Diels-Alder reaction with /V-phenylmaleimidc has frequently been used for the separation, purification, and structure determination of ortho photocycloadducts [12,47,86,90,108,116,126,132,133,138], Other dienophiles that have been successfully employed in Diels-Alder reactions with ortho adducts are A-(para-bromophenyl)maleimide [116,120], maleimide [116,118,127], maleic anhydride [127,191], tetracyanoethylene [11], and dimethyl acetylenedicarboxy-late [73,127], The Diels-Alder product of A-(para-bromophenyl)maleimide with the exo-ortho adduct formed from 1,4-dioxene and benzene [120] and the Diels-Alder product of maleimide with the endo-ortho adduct from cis-cy-clooctene and benzene [118] were obtained in crystalline form and their structures could be determined by means of x-ray diffraction. 

A cyclooctatriene was formed upon pyrolysis at high temperature (up to 350°C) of the exo-ortho adduct from benzene and 1,4-dioxene [12] the position of the double bonds, however, was not as expected for a ring-opened ortho adduct. The ortho adduct from benzene and 1,1-dimethoxyethene [12] is an acetal and with a trace amount of acid in methanol solution it is converted into cycloocta-2,4,6-trien-l-one (Scheme 50). 

The ability to overcome MDR in many 1,4-DHPs varies considerably with the nature of the 3,5-substituents. The pyridylalkyl esters are specially suitable, as in the case of NIK-250 (46) [82,83] related derivatives bearing dihydro-1,4-dioxene, dihydro-1,4-dithiane or dihydropyran substituents at C-4 [84]. Other representatives of this group that contain an alkyl group at C-4 (19 (47)) have also shown potent and selective anti-MDR activity [85]. Compounds PAK-200 (48) [86,87] and PAK 104P (49) [88] exemplify the absence of correlation between calcium channel and MDR antagonism, since neither N-alkyl-l,4-DIIPs nor pyridines have significant calcium channel-blocking activity. 

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