Chrysenes, synthesis

The synthetic procedure described is based on that reported earlier for the synthesis on a smaller scale of anthracene, benz[a]anthracene, chrysene, dibenz[a,c]anthracene, and phenanthrene in excellent yields from the corresponding quinones. Although reduction of quinones with HI and phosphorus was described in the older literature, relatively drastic conditions were employed and mixtures of polyhydrogenated derivatives were the principal products. The relatively milder experimental procedure employed herein appears generally applicable to the reduction of both ortho- and para-quinones directly to the fully aromatic polycyclic arenes. The method is apparently inapplicable to quinones having an olefinic bond, such as o-naphthoquinone, since an analogous reaction of the latter provides a product of undetermined structure (unpublished result). As shown previously, phenols and hydro-quinones, implicated as intermediates in the reduction of quinones by HI, can also be smoothly deoxygenated to fully aromatic polycyclic arenes under conditions similar to those described herein. 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

An alternative new synthetic approach to chrysene 1,2-dihydro-diol based on Method IV has recently been developed (60). This method (Figure 12) entails synthesis of 2-chrysenol via alkylation of 1-1ithio-2,5-dimethoxy-1,4-cyclohexadiene with 2-(1-naphthyl) e-thyl bromide followed by mild acid treatment to ge nerate the diketone 12. Acid-catalyzed cyclization of 12 gave the unsaturated tetracyclic ketone 13 which was transformed to 2-chrysenol via dehydrogenation of its enol acetate with o-chloranil followed by hydrolysis. Oxidation of 2-chrysenol with Fremy s salt gave chrysene... 

Figure 11. Synthesis of the chrysene 1,2- and 3,4-dihydrodiols and the corresponding diol epoxide derivatives from chrysene by Method III (50. Reagents (i) H2,Pd (ii) H2,Pt (iii) DDQ (iv) AgOBZ,I25 (v) NBS A.

Figure 12. Synthesis of chrysene 1,2-dihydrodiol by Method IV (52). Reagents (i) H (ii) isopropenyl acetate (iii) DDQ (iv) (KS03)2N0 (v) NaBH4,02.

S. Yamaguchi and T.M. Swager, Oxidative cyclization of bis(biaryl)acetylenes synthesis and photophysics of dibcnzo, /j]chrysene-based fluorescent polymers, J. Am. Chem. Soc., 123 12087-12088, 2001. 

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... 

Many polycyclic aromatic amines and aldehydes are commercially available, but their supply is very limited. Preparation of these starting materials is necessary for studying the (3-lactam formation reaction [93]. Nitro compounds are the precursors for the amines. An important task was to prepare polycyclic aromatic nitro compounds, particularly those of chrysene, phenanthrene, pyrene, and dibenzofluorene in good yield. Nitration of these hydrocarbons with concentrated nitric acid in sulfuric acid is a widely used reaction for this purpose. Our research culminated in facile synthesis of polyaromatic nitro derivative 9 starting from polyaromatic hydrocarbons (PAHs) 8 through the use of bismuth nitrate impregnated with clay (Scheme 1) ([94, 95] for some examples of bismuth nitrate-catalyzed reactions... 

Intramolecular cyclisation of a 4-arylbutanoic acid system is also an important step in a convenient synthesis of the polycyclic system, chrysene, which is formulated and described in Expt 6.12. Here, methyl cinnamate is first subjected to reductive dimerisation to give methyl meso-ft,y-diphenyladipate, which is accompanied by some of the ( + )-form. The meso isomer (16) is the most easily isolable and cyclisation occurs smoothly in sulphuric acid to yield the diketone 2,1 l-dioxo-l,2,9,10,ll,18-hexahydrochrysene, which is obtained as the trans form (17) as shown in the following formulation. Clemmensen reduction of this ketone followed by dehydrogenation (in this case using selenium) completes the synthesis of chrysene. 

The Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

Apart from the construction of phenanthrenes, carbene complexes have also been used for the synthesis of more extended polycyclic arenes. An unusual dimerization of chromium coordinated ortbo-ethynyl aryl carbenes results in the formation of chrysenes (Scheme 37) [81]. This unusual reaction course is presumably due to the rigid C2 bridge that links the carbene and alkyne moieties, and thus prevents a subsequent intramolecular alkyne insertion into the metal-carbene bond. Instead, a double intermolecular alkyne insertion favored by the weak chromium-alkyne bond is believed to occur forming a central ten-membered ring that may then rearrange to the fused arene system. For example, under typical benzannulation conditions, carbene complex 97 affords an equimolar mixture of chrysene 98a and its monochromium complex 98b. The peri-interactions between the former alkyne substituent (in the 5- and 11-positions) and the aryl hydrogen induce helicity in the chrysene skeleton. 

Problem 30.30 Outline a possible synthesis of chrysene by the Bogert-Cook method (Problem 30.27, p. 944), starting from naphthalene and using any aliphatic or inorganic reagents. Hint See Problem 30.7(g), p. 977.)... 

ProUem 30.31 Outline an alternative synthesis of chrysene by the Bogert-Cook methodi starting from benzene and using any aliphatic or inorganic reagents. 

Wilds, A. L., Djerassi, C. Dienone-phenol rearrangement applied to chrysene derivatives. The synthesis of 3-hydroxy-1-methylchrysene and related compounds. J. Am. Chem. Soc. 1946, 68, 1715-1719. 

PAHs appear to affect other blood elements, as well. The influence of several PAHs on calcium ionophore-induced activation of isolated rabbit platelets was studied (Yamazaki et al. 1990). The activation of the platelets was assessed by measuring thromboxane 62 synthesis in response to stimulation by the calcium ionophore, A-23187. The authors reported that thromboxane 62 synthesis was inhibited by incubation of the stimulated platelets with benz[a]anthracene, chrysene, benzo[a]pyrene, and benzo[g,h,i]perylene, and stimulated by incubation with anthracene and pyrene. However, no statistical analysis was performed on these data, and the changes reported are generally within 10% of control values. In addition, the effects of the PAHs on thromboxane B2 synthesis are bidirectional, and in many instances, the same compound induced both inhibition and stimulation at different concentrations. 

The thermal disrotatory [n6] electrocyclization of cis-1,3,5-hexatriene systems has been extensively employed for the synthesis of cyclic hydrocarbons. The average enthalpy of activation is in the range of about 120 kJ mol 1 [36]. The incorporation of two of the hexatriene double bonds in phenyl rings (stil-bene, 1) stabilizes the precursor significantly and necessitates temperatures of 1050°C to obtain a 30% yield of phenanthrene (2, see Scheme 2, [37]). An enthalpy of activation of (250 20) kJ mok was estimated for the conversion of 9,9 -bifluorenylidene (3) to benz[e]indeno[l,2,3-hi]acephenanthrylene (4), a reaction that is accompanied by the radical initiated isomerization of 3 to diben-zo[g,p]chrysene (5, Scheme 2, [38]). It is assumed that both reactions 1 —> 2 and 3 —> 4 are initiated by an electrocyclic ring closure forming a 4 a,4 fr-dihydro-phenanthrene (la) intermediate. 

Numerous aromatic compounds including several bowl-shaped fullerene fragments have been prepared by this method, e.g. cyclopenta[z/]fluoranthene (22, Scheme8, [54d,56a]), cyclopenta[bc]corannulene (23, [55a]) and diace-naphtho[3,2,l,8-cdejg 3, 2, l, 8 -Zmnop]chrysene (24, see Scheme 9, [55b,c]). Of special importance is this approach for the synthesis of cyclopenta-annelated PAHs, e.g. and the three isomeric dicyclopentapyrenes (25-27, Scheme 9, [54e, 56b]). Using these reference samples, several cyclopenta-annelated PAHs could be identified as byproducts formed in the incomplete oxidation of hydrocarbons in fuel rich flames [57]. 

Irradiation of ort/zo-diarylarenes (e.g. o-terphenyls) results exclusively in condensed PAH as products from photocyclization reactions (e. g. triphenyl-enes, see [84]) and, of course, no [2+ 2]cycloaddition is observed. This fact enables the use of higher concentrations of ortho-diarylarenes compared to stilbenes in a photocyclization reaction as outlined in Scheme 16 for the synthesis of benzo[c]naphtho[2,1 -p]chrysene (15b) from 1,3,5-tristyrylbenzene (38, c <0.2 mmol 1 1 [85]) or 1,2 l, 2"-ternaphthalene (39, c = 20 mmol 1 1 [84 c]) respectively. If higher concentrations of 38 were applied, [2 + 2] cycloaddition reactions yielding multibridged cyclophanes were observed almost exclusively [85]. 

Scheme 58. Novel synthesis of centrosymmetric chrysenes (127) by dimerization of intramole-cularly stabilized alkyne-carbene chromium chelate complexes [160a, d]...

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