Synthesis of dibenzo[def,p]chrysene, its active metabolites, and their 13C-labeled analogues

Dibenzo[def,p]chrysene (DBC) is a highly carcinogenic polycyclic aromatic hydrocarbon suspected to be involved in initiation of lung cancer in smokers. Efficient new syntheses of DBC, its active metabolites [DBC diol (1), DBC dione (2), DBC diol epoxide (3)], and their previously unknown 13C2-labeled analogues are reported. The 13C2-labeled analogues are required as standards for sensitive methods of analysis of their DNA adducts in human cells using stable isotope dilution liquid chromatography/tandem mass spectrometry.     

The molecular and electronic structure of dibenzo[g,p]chrysene: A twisted case

Summary Studies of the electronic structure and spectrum of dibenzo [g,p]chrysene, carried out in 1965 and 1985, were not fully conclusive. They are repeated here by means of improved linear dichroism spectroscopy, quantum mechanical calculations of the spectra, and structural studies. Based on the new evidence, especially the observed transition moment directions, it is concluded that the molecule is nonplanar with D₂ symmetry. The experimentally determined transition moment directions also allow a complete assignment of all significant transitions in the region 25 000 to 45 000 cm^–1. All three possible (perpendicular) transition moment directions are represented among the observed electronic transitions.Dedicated to Jan Linderberg on the occasion of his 60th birthday     

Vibrational and electronic absorption spectroscopy of dibenzo[b,def]chrysene and its ions

The vibrational and electronic absorption spectra of dibenzo[b,def]chrysene (DBC) and its ions in argon matrixes have been recorded. Assignment of the observed infrared (IR) bands has been made by comparison with the density functional theory (DFT) computations of harmonic vibrational frequencies (with 6-31G(d,p) or 6-311+G(d,p) basis sets). Extensive time-dependent (TD) DFT calculations of vertical excitation energies have aided in the assignment of the experimental electronic absorption transitions. In general, the theoretical predictions are in good agreement with the observed ultraviolet and visible bands. By correlating IR and UV-visible band intensities (after UV photolysis), it has been shown that both DBC cations and anions are formed. The IR band intensity distributions of the DBC ions differ markedly from neutral DBC. A synthetic spectrum composed of neutral, cationic, and anionic DBC contributions compares reasonably well with the interstellar features of the "unidentified infrared" (UIR) bands from the reflection nebula NGC 7023. Finally, it is shown that the electronic absorption bands of the DBC ions lie in close proximity to several of the diffuse interstellar visible absorption bands (DIBs).     

A New and Concise Synthesis of 3-Hydroxybenzo[c]phenanthrene and 12-Hydroxybenzo[g]chrysene, Useful Intermediates for the Synthesis of Fjord-Region Diol Epoxides of Benzo[c]phenanthrene and Benzo[g]chrysene

A new strategy which involves a palladium-catalyzed cross-coupling reaction has been developed for the rapid synthesis of 3-hydroxybenzo[c]phenanthrene (5) and 12-hydroxybenzo[g]chrysene (6). These phenolic compounds are the key intermediates for the synthesis of highly carcinogenic fjord-region diol epoxide metabolites 3 and 4 of benzo[c]phenanthrene (1) and benzo[g]chrysene (2). The cross-coupling reaction of 2-bromo-5-methoxybenzaldehyde (9) with naphthalene-1-boronic acid (7) and phenanthrene-9-boronic acid (8) produced 2-(1-naphthyl)-5-methoxybenzaldehyde (10) and 2-(9-phenanthryl)-5-methoxybenzaldehyde (11), respectively, in quantitative yields. After reaction of these aldehydes with trimethylsulfonium iodide under phase-transfer conditions or with the Wittig reagent obtained from (methoxymethyl)triphenylphosphonium bromide and phenyllithium to generate an oxiranyl or methoxyethene side chain, the acid-catalyzed cyclization with methanesulfonic acid (or boron trifluoride) produced 3-methoxybenzo[c]phenanthrene (16) and 12-methoxybenzo[g]chrysene (17) in 61-64% yields. Finally, demethylation of these methoxy derivatives 16 and 17 with boron tribromide resulted in the formation of the hydroxy analogues 5 and 6, respectively. The availability of this short and high-yielding regiospecific method for the synthesis of phenols 5 and 6 should allow the preparative-scale synthesis of the fjord-region diol epoxides 3 and 4. These diol epoxides are required as starting compounds for the synthesis of site-specifically modified oligonucleotides which are critically needed to elucidate the mechanism of carcinogenesis at the molecular level.     

Diindeno-Fused Dibenzo[a,h]anthracene and Dibenzo[c,l]chrysene: Syntheses,Structural Analyses,and Properties

Diindeno-fused dibenzo[a,h]anthracene 6 and diindeno-fused dibenzo[c,l]chrysene 9 contain the key moieties 1,4-quinodipropene (1,4-QDP) and 2,6-naphthoquinodipropene (2,6-NQDP), respectively, and they both have an open-shell singlet ground state. The latter compound exhibits a strong biradical character and interesting properties, including a low ΔE_T−S (2.44 kcal mol⁻¹), a small HOMO–LUMO gap (1.06 eV), a wide photoabsorption range (250–1172 nm), and a large two-photon absorption cross-section (σ=1342±56 GM). This work verifies that 6 has a slightly larger HOMO–LUMO gap and ΔE_T−S than its helical isomer diindeno[2,1-f:1′,2′-j]picene (DIP), but is a much stronger two-photon absorber, verifying the important effect of geometry on the photophysical properties.     

Barriers to ring inversion in dibenzo[a,c]cyclooctene and its dihydro and tetrahydro derivatives by racemization and NMR bandshape studies

Dibenzo[a,c]cyclooctene and its 9,10-dihydro and 9,10,11,12-tetrahydro derivatives have been resolved by chromatography and their inversion barriers determined by thermal racemization. The 9,12-dihydro derivative has been studied by ¹H NMR bandshape technique.     

Phenanthrene-fused azo-ene-ynes: synthesis of dibenzo[f,h]cinnoline and dibenzo[e,g]isoindazole derivatives

The cyclization reactions of a phenanthreno-fused azo-ene-yne compound have been studied both experimentally and computationally. Experimental results show that this system is prone to dimerization, more so than previously studied naphthalene- and benzene-based analogues. Calculations reveal that pyrazoles and arene-fused pyrazoles strongly stabilize carbenes in the 5-position through "coarctate conjugation", suggesting a stationary concentration of the carbenes/carbenoids during cyclization that is high enough for dimerization.     

New synthetic approaches to polycyclic aromatic hydrocarbons and their carcinogenic oxidized metabolites: derivatives of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene

A new synthetic approach to polycyclic aromatic compounds is described that entails in the key steps double Suzuki coupling of PAH bisboronic acid derivatives with o-bromoaryl aldehydes to furnish aryl dialdehydes that are converted to larger polycyclic aromatic ring systems by either (a) conversion to diolefins by Wittig reaction followed by photocyclization or (b) reductive cyclization with triflic acid and 1,3-propanediol. This synthetic method provides convenient access to as many as three different polycyclic aromatic ring systems from a single Suzuki coupled intermediate. It was utilized to synthesize substituted derivatives of benzo[s]picene, benzo[rst]pentaphene, dibenzo[b,def]chrysene, and 13,14-dihydro-benz[g]indeno[2,1-a]fluorene, as well as the putative carcinogenic bisdihydrodiol metabolites of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene.     

Convenient syntheses of benzo-fluorinated dibenz[b,f]azepines: rearrangements of isatins, acridines, and indoles

Efficient procedures for the synthesis of benzo-fluorinated dibenz[b,f]azepines (iminostilbenes) from fluorinated isatins or indoles using a number of ring-expansion reactions are described. A range of mono- and difluorinated analogues is accessible, and the syntheses can deliver gram quantities of the final products, which are precursors of fluoro analogues of the important anticonvulsant carbamazepine.     

A comprehensive study of isoskeletal analogs of dibenzo[a,c]anthracene

While reviewing the chemistry of cyclopentadienone derivatives and aza isoskeletal analogs of dibenzo[a,c]anthracene, additional molecular orbital (MO) and spectroscopic results and insights are presented. The MO tendency for coplanarity of phenyl substituents on benzenoids is demonstrated. Perpendicularly oriented phenyl substituents resulting from steric interactions strongly shield appropriately situated protons in NMR spectra. The principles of alternating polarity and parallel correspondence in conjunction with MO methods are used to relatively order aza arene isoskeletal analogs according to their chemical properties. Since less than 1.87% of the isoskeletal analogs of benzo[a,c]-anthracene have been reported, this summary work will help one to forecast the major chemical properties of those not yet synthesized.A preliminary account of this work was presented at the 23rd ACS Midwest Regional Meeting, University of Iowa, Iowa City, Nov. 17, 1988     

Functionalized dibenzo[g,p]chrysenes: variable photophysical and electronic properties and liquid-crystal chemistry

The photophysical and electronic properties of dibenzo[ g, p]chrysenes bearing electron-rich and -deficient substituents vary markedly with these substituents. The chemistry of the first liquid-crystalline dibenzo[ g, p]chrysene is also described.     

Platinum complexes of dibenzo[1,2]dithiin, dibenzo[1,2]dithiin oxides and related polyaromatic hydrocarbon ligands

The synthesis of platinum bisphosphine complexes of biphenyl- 2,2'-dichalcogenates and the oxides of dibenzo[1,2]dithiin and related ligand systems by oxidative addition to [Pt(PPh(3))(4)] is reported. We also describe the synthesis of a new compound, dibenzothiophen-4-yldiselenide and its simple platinum complex (obtained by oxidative addition). All complexes have been fully characterised, principally by using multinuclear NMR spectroscopy and in six cases by means of single-crystal X-ray diffraction studies. The majority are simple S/S or Se/Se complexes, however the addition of dibenzo[1,2]dithiin trioxide to [Pt(PPh(3))(4)] gives a bimetallic system, [Pt[2-[S(O)],2'-[S(O)(2)]-biphen}(PPh(3))](2), containing a central Pt(2)S(2)O(2) core in which the ligand behaves as a tridentate S,S,O donor.     

A Highly Abbreviated Synthesis of Dibenzo[def,p]chrysene and Its 12-Methoxy Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate Carcinogens of Dibenzo[def,p]chrysene

Dibenzo[def,p]chrysene (DBC) (1), is by far the most mutagenic and toxic polycyclic aromatic hydrocarbon identified. Its metabolic activation leads to trans-11,12-dihydroxy-11,12-dihydro-DBC (2), which is further metabolized to the ultimate metabolite, anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DBC (3), that binds to DNA causing mutations and ultimately tumor induction. We report a facile route for the syntheses of DBC (1) and its 12-methoxy derivative (12-methoxy-DBC) (13), a key intermediate for the synthesis of 2 and 3, using a Suzuki cross-coupling approach.     

Spectroscopic and electrochemical properties of cyclopalladated complexes based on dibenzo[a,c]phenazine

Cyclopalladated complexes based on dibenzo[a,c]phenazine were studied by ¹H NMR and electronic absorption and emission spectroscopy, and cyclic voltammetry. Replacement of ethylenediamine by heterocyclic ligands scarcely affects the coordination-induced proton shifts of the diazine part of the cyclometalated ligand, but, as the basicity of chelated ligands decreases, the screening of protons of the carbanionic part of those cyclometalated ligands which is the most proximate to the coordination center regularly decreases. Cyclopalladation reveals itself in the following characteristic parameters of photo-and electro-induced electron-transfer processes: longwave absorption band, λ_max (437±7) nm and ε (3.0±1.5) × 10³ l mol^?1 cm^?1, vibration-structured low-temperature luminescence resulting from spin-forbidden optical transition from the excited to ground state of the complex with the energy E ^∞ (16.98±0.03) kK and the lifetime τ (190±20) μs, and reversible one-electron electroreduction wave with E _1/2 ?(1.39±0.03) V.     

Functionalized derivatives of dibenzo [c,j] dipyrazolo-[3,4-f∶3′,4′-m] [1,2,5,8,9,12] hexaazacyclotetradecinate

A number of derivatives of dibenzo [c,j] dipyrazolo [3,4-f3,4-m] [1,2,5,8,9,12]-hexaazacyclotetradecinate with peripheral nitro, amino, and acetylamino groups have been synthesized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 106–114, January, 1984.     

Mass spectral fragmentation mechanisms of some dibenzo[c,f][1,2] diazepines

The fragmentation mechanisms of 11H-dibenzo[c,f][1,2]diazepine (I), its 3,8-dichloro derivative (II), 3,8-dichlorodibenzo[c,f] [1,2]diazepin-11-one (III) and 3,8-dichloro-11H-dibenzo-[c,f][1,2]diazepin-N-oxide (IV) are discussed. The initial loss of molecular nitrogen is characteristic of I, II and III. Compound IV has a strong molecular ion, that competitively eliminates cither NO or Cl- and N₂O. The common radical ion, m/166 e present in the mass spectra of I, fluorene, 2-methyl-9,10-anthraquinone and 2-methylbenzo[c]cinnoline, appears to be formed in different states.     

Efficient dibenzo[c]acridine helicene-like synthesis and resolution: scaleup, structural control, and high chiroptical properties

Herein, we describe our recent expeditious synthesis of dibenzo[c]acridine helicene-like compounds on a large scale in pure enantiomeric form. This flexible synthesis allows for variation at several positions on the skeleton. Geometrical parameters related to these compounds have been obtained from monocrystal X-ray structure resolution. Additionally, chiroptical parameters have been recorded, highlighting the versatility of this family showing for example optical rotation at 589 nm varying between 135 and 150 deg g(-1)cm(2).