Stilbenes phenanthrenes

Benzene, toluene, anthracene, phenanthrene, biphenyl. Aromatic hydrocarbons with unsaturated side-chains. Styrene, stilbene. 

The reaction of cinnoline 2-oxide with phenylmagnesium bromide gives phenanthrene, trans- and cfs-stilbene, 2,3-diphenyl-l,2-dihydrocinnoline and 2-styrylazobenzene in yields of 1-15%. Analogous results are also obtained from 4-methylcinnoline 2-oxide. 

As discussed in Section 10.3, the system consisting of a diazonium ion and cuprous ions can be used for hydroxy-de-diazoniation at room temperature in the presence of large concentrations of hydrated cupric ions (Cohen et al., 1977 see Schemes 10-7 to 10-9). With (Z)-stilbene-2-diazonium tetrafluoroborate under these conditions, however, the major product of ring closure of the initially formed radical was phenanthrene (64%). When the cupric nitrate was supplemented by silver nitrate the yield increased to 86% phenanthrene. Apparently, the radical undergoes such rapid ring closure that no electron transfer to the cupric ion takes place. 

Figure 6.10. Rate constants for quenching of sensitizers by cis- and trans-stilbenes (open and filled circles, respectively). Sensitizers are as follows (1) tri-phenylene, (2) thioxanthone, (3) phenanthrene, (4) 2-acetonaphthone, (3) 1-naphthyl phenyl ketone, (6) crysene, (7) fluorenone, (8) 1,2,5,6-dibenzanthracene, (9) benzil, (10) 1,2,3,4-dibenzanthracene, (11) pyrene, (12) 1,2-benzanthracene, (13) benzanthrone, (14) 3-acetyl pyrene, (15) acridine, (16) 9,10-dimethyl-l,2-benzanthracene, (17) anthracene, (18) 3,4-benzpyrene.<57> Reprinted by permission of the American Chemical Society.

The photochemical isomerization of E-stilbenes has been applied in the preparation of phenanthrenes, as Z-stilbenes undergo electrocyclie ring closure (cf. chapter 3.1.3) to dihydrophenanthrenes which in turn are easily oxidized to phenanthrenes (3.1) 305). This sequence has also been employed in the synthesis of benzoquinolines 306) or of benzoquinolizines (3.2) 307). 

The most famous of these compounds is combretastatin A-4 (CA-4,7), isolated by Pettit et al. in 1989 [30]. Pettit s research led to the isolation and structural determination of a series of phenanthrenes, dihydrophenanthrene, stilbene, and bibenzyl compounds [31]. CA-4 (7), alongside CA-1 (8), was found to be an extremely active inhibitor of tubulin polymerization [30,32]. The major problems associated with these compounds were poor bioavailability and low aqueous solubility [33,34], and hence, research in the field was turned to designing better alternatives with the hope of eradicating the negative properties of these potent compounds. 

In the pioneering papers of Wawzonek et al. [18, 214] it was demonstrated that CO2 can be added to cathodicaUy reduced hydrocarbons to yield dihydrodi-carbonylates. Examples of this kind of reaction include naphthalene [215-220], anthracene [18], 9,10-diphenylanthracene [18], phenanthrene [215, 216], butadiene [217-220], stilbene [18], and diphenyl... 

Reduction of stilbene [18] or dipheny-lacetylene [214] in DME yields 1,2,3,4-tetraphenylbutane, whereas phenanthrene [214] provides 9,9, 10,10 -tetra-hydro-9.9 -biphenanthrene. Hydrodimerization was also observed with benzalfluo-rene [225]. If DME is replaced by acetonitrile, protonation completely dominates hydrodimerization [18]. In carefully dried ethers, using alkali or alkaline earth metals salts as supporting electrolyte, 1,1-diphenylethylene can be reduced ca-thodicaUy to give stable solutions of 1,1,4,4-tetraphenylbutane dianions [226]. These dianions can be cleaved by flash... 

Phosphorane, (dichloromethylene) TRIPHENYL-1, 46, 33 Phosphorus pentachloride, for conversion of D,L-10-camphorsulfonic acid to acid chloride, 46,14 reaction with styrene, 46, 99 Photolysis of substituted stilbenes to phenanthrenes, 46, 91... 

The photocyclization has been found not to occur with stilbenes substituted with acetyl, dimethylamino, or nitro groups, lodo substituents are replaced by hydrogen by photolysis in cyclohexane solution. w-Substituted stilbenes give mixtures of 2- and 4-substituted phenanthrenes which generally are difficult to separate. 

Cohare and co-workers reported that aristolactam BU (22) was prepared, following Kupchen s method, by Perkin condensation of 6-bromo-3,4-di-methoxy phenyl acetic acid (119) and o-nitrobenzaldehyde (120) (Scheme 14). The 2-bromo-4,5-dimethoxy-2 -nitro-ds-stilbene-a-carboxylic acid (121) was obtained. The nitro group of 121 was reduced with ferrous sulfate and ammonium hydroxide, and the resulting 2-bromo-4,5-dimethoxy-2 -amino-cw-stilbene-a-carboxylic acid (122) without purification was submitted to the Pschorr phenanthrene synthesis to yield l-bromo-3,4-dimethoxyphen-anthrene-lO-carboxylic acid (123). The phenanthrylamine 124 was prepared from 123 via a Schmidt reaction, and, by treatment with n-butyllithium and CO2, 124, afforded 22 (42). 

This yellow coloration is undoubtedly due to DHP (i), whose oxidation product, phenanthrene, was observed by Smakula as an oxidation product in the photolysis of cis-stilbene ... 

The valence tautomerism 251 257 has been proposed to account for the formation of iV-methylthiobenzamide by irradiation (2537 A) in methyl cyanide solution. The valence tautomer 257, R = Me, = Ph, has been detected spectroscopically (p , 2060 cm —N=C=S) either during photolysis at 25° or by heating at 160°. Photochemical oxidative cyclization of 4,5-diaryl derivatives (251, R = R = Ar) analogous to the formation of phenanthrene from stilbene has been reported. Thus, irradiation of the 4,5-diphenyl derivative 251, R = R = Ph, yields the tetracyclic meso-ionic compound (258). ... 

Als Nebenprodukte werden cis-Stilben und Phenanthren (2) zusam-men mit anderen Produkten erhalten. 

The photochemical synthesis of helicenes by irradiation of 1,2-diarylethylenes in adilute solution and in the presence of an oxidizing agent is based on the well known photocyclodehydrogenation of stilbene into phenanthrene. There is an overwhelming amount of literature on this type of photoreaction. Details about scope and limitation can be found in previous reviews 7,8). Therefore, only a short survey will be given of the mechanism of the reaction. 

In the presence of an oxidizing species (oxygen, iodine, tetracyanoethylene and others) DHP is dehydrogenated into phenanthrene. This oxidation can also be thermal or photochemical. In general, meta substituted stilbenes give rise to two isomeric substituted phenanthrenes ortho-substituted stilbenes can lose the substituent on cyclization. 

Fig.6 The distance dependence of electron-transfer rates in DNA hairpins [51]. The acceptor is a photoexcited derivatized stilbene (SA) or phenanthrene (PA) the electron donor is guanine (G), deazaguanine (Z), or inosine (I). The decay is much more rapid in the Z-PA couple compared to the G-SA couple because the tunneling energy is further from the bridge states in the case of Z-PA...

The l,3,5-triene-l,3-cyclohexadiene interconversion is a six-electron electrocycli-zation that requires a cis central double bond to occur.245 An important application of this rearrangement is the photocyclization of cis-stilbene to dihydrophenanthrene [Eq. (4.45)], which is usually further oxidized to phenanthrene 249... 

There are a large number of photochemical cydizations of aromatic compounds that lead initially to polycyclic, non-aromatic products, although subsequent rearrangement, elimination or oxidation occurs in many instances to form aromatic secondary products. The archetype for one major class of photocydization is the conversion of stilbene to phenanthrene by way of a dihydrophenanthrene (3.60). 

A very large number of substituted phenanthrenes have been made from stilbenes by this photocydization method, as have more complex polycyclic aromatic compounds by related reactions involving a single cydizatlon (e.g. 3.64 for chrysenes) or two, or more, successive cydizations le.g. 3.65). The reaction can be nicely adapted to provide a route from 1-benzylidenetetra-hydroisoquinolines to alkaloids of the aporphine family (e.g. 3.66). 

A number of l-aryl-2-thienylethylenes have been photocyclized in the presence of an oxidizing agent (usually iodine) to polycyclic aromatic compounds. Representative examples are given in Table 1. The mechanism, as with the conversion of stilbene to phenanthrene, probably involves conversion of the trans-alkene to the c/s-form, cyclization to the dihydro isomer, and oxidation of the latter to the fully aromatic compound. The yield of the cyclized product seems to decrease when the ethylene is attached to the /3-position of the thiophene. 

Stilbenes and associated molecules provide very good examples of the formation of intermediate unstable isomers which give a chemical route for internal conversion. Upon irradiation, stilbenes undergo a cis-trans isomerization as the predominant reaction. However, under oxidative conditions phenanthrene is also formed.12 It was shown that the phenanthrene came only from c/s-stilbene (13),61 and that an intermediate unstable isomer, nms-dihydrophenanthrene (14), was the precursor of the phenanthrene.62-64 The dihydrophenarithrene was in its ground state, but vibrationally excited, and was formed by a process calculated to be endothermic by 33 10 kcal/mole-1.02 Oxygen or other oxidants converted it to phenanthrene (15), but in the absence of oxidants it was either collisionally stabilized or reverted to m-stilbene. 

In the vapor phase phenanthrene and hydrogen were products of the photolysis of c/.v-stilbene in addition to the expected mww-stilbene.65 The photolysis of 1,4-diphenyl-1,3-butadiene to give a-phenylnaphtha-lene is an analogous process.65 It was proposed that the intermediate dihydrophenanthrene was a cis form.66... 

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