Biphenyl compounds

FIGURE I.I6 Isomers of biphenyl compounds with bulky groups attached at the ortho positions. 

It is known that the brain is one of the most sensitive sites of action of steroids in utero, and recently there have been suggestions that EDs may affect normal brain development and behaviour. For example, it has been alleged that in utero exposure to polychlorinated biphenyl compounds (PCBs) resulted in adverse effects on neurologic and intellectual function (memory and attention) in young children born to women who had eaten PCB contaminated fish in the USA." It has also been speculated that exposure to environmental pollutants with steroidal activity may be infinencing human sexual development and sexually controlled behavioiir." ... 

The products 4 are formed as racemic mixtures, but can be resolved by recrystallization of diastereomeric salts.23 - 25 Syntheses starting from optically active biphenyl compounds are also known.26 -28 l,l -Binaphthyl-2,2 -diamine(5) can be transformed to the dinaphtho[1,4]di-azocine 6 by melting with benzil.29... 

Nebeker, A.V., Puglisi, E.A., and Defoe, D.L. (1974). Effect of polychlorinated biphenyl compounds on survival and reproduction of fathead minnow and llagfish. Transactions of the American Fisheries Society 103, 562-568. 

Aromatic side chains of amino acids such as phenylalanine, tryptophan, and tyrosine are found in general in the interior of proteins, in hydrophobic regions. In some proteins they mediate helix-helix contacts. It is to be expected that agents containing aromatic groups could interact with proteins via aromatic-aromatic interactions, as for instance, proven by X-ray studies of biphenyl compounds which inhibit sickle-cell hemoglobin gelation. 

Switching from the biphenyl core to a 3-phenylpyridine core resulted in compounds that were similar in potency to the biphenyl compounds, but with increased inhibition of ACC2 versus ACC1, as... 

Mehendale HM. 1976. Mirex-induced suppression of biliary excretion of polychlorinated biphenyl compounds. Toxicol Appl Pharmacol 36(2) 369-381. 

OT-CEC modified with different surface moieties (butylphenyl, cholesteryl, and biphenyl compounds)... 

The Friedel-Crafts cyclization of biphenyl-2-sulfonyl chloride to give dibenzothiophene sulfone has been described (55%) ° however, thermal cyclization in octachloronaphthalene at 250°, under nitrogen, is reported to yield dibenzothiophene itself rather than the sulfone (47%). Reaction of biphenyl compounds with oleum (H2SO4 + SO3) to yield derivatives of dibenzothiophene 5,5-dioxide is widely used for the preparation of dyestuff intermediates (Section VI, E, 2). A typical example is shown in Eq. (3), starting from o-tolidine. ... 

The 4 -substituted biphenyl compounds were included in this study by subtracting the length of hydrogen (2.06) from the STERIMOL length of benzene (6.28) and adding on the STERIMOL length of the 4 -substituent. 

The chirality observed in this kind of substituted allene is a consequence of dissymmetry resulting from restricted rotation about the double bonds, not because of a tetrahedral atom carrying four different groups. Restricted rotation occurs in many other kinds of compounds and a few examples are shown in Table 13-3, which includes trans-cycloalkenes (Section 12-7), cycloalkyli-denes, spiranes, and ort/zo-substituted biphenyl compounds. To have enantiomers, the structure must not have a plane or center of symmetry (Section 5-5). 

Degradation of polychlorobiphenyls (PCBs) by zero-valent iron requires temperatures of 400°C (Grittini et al., 1995). At 400°C, PCBs are reduced to biphenyls. For further degradation of the biphenyl compound, temperatures have to exceed 500°C (Chuang et al., 1995). Under normal temperatures, zero-valent iron has little effect on PCBs. 

PCBs were manufactured and sold under many names, even if the most common are the Aroclor series. Aroclor refers to a mixture of individual chlorinated biphenyl compounds with different degrees of chlorination. A PCB mixture with an Aroclor name usually includes a numerical identifier, which provides additional information on the properties of the mixture. The most common mixtures in the Aroclor series are Aroclor 1016, Aroclor 1242, Aroclor 1248, Aroclor 1254 and Aroclor 1260. 

Johnstone, G.J., Ecobichon, D.J., Hutzinger, O. (1974) Effects of pure polychlorinated biphenyl compounds on hepatic function in the rat. Toxicol. Appl. Pharmacol. 28, 66-81. 

For the preparation of biphenyl compounds with substituents in only one ring, it is usually advisable to employ a substituted aniline and couple with benzene rather than to use aniline and couple with a benzene derivative, since with benzene only a single biaryl compound is produced. Thus, 4-methylbiphenyl can be isolated readily in pure form from the reaction between diazotized p-toluidine and benzene, but not from the mixture of 2- and 4-methylbiphenyl formed from diazotized aniline and toluene. 

Alkoxy derivatives of biphenyl can be obtained either from alkoxy-anilines or by coupling with alkoxybenzenes. From diazotized p-bromo-aniline and anisole a 20% yield of 4-bromo-2 -methoxybiphenyl and a 7% yield of 4-bromo-4 -methoxybiphenyl are obtained. In connection with their studies on Cannabis Indica, Ghosh, Pascall, and Todd u prepared the highly substituted biphenyl compound, 2-cyano-5-methyl-2, 5 -dimethoxy-4 -n-amylbiphenyl (VII), in 27% yield from the nitrosoacetyl derivative of 2-cyano-5-methylaniline and 2,5-dimethoxy-n-amylben-zene. 

The Ullmann reaction appeared to be the only satisfactory method for preparing certain highly substituted unsymmetrical biphenyl derivatives which were required by Adams and coworkers 46 in their study of the stereoisomerism of biphenyl compounds. 

The absolute configuration of piperidine Lythrum alkaloids was established by analysis of ORD and CD spectra of biphenyl compounds. 

Scheme 15.4 Synthesis of biphenyl compounds via ligand-free Suzuki coupling.

Wu QX, Majid A, Marshall WD. Reductive dechlorination of polychlorinated biphenyl compounds in supercritical carbon dioxide. Green Chem 2000 2 127-132. 

Workers at Sphinx [24] have published a synthetic route to a series ofhighly functionalized biphenyl compounds. The key reactions in this sequence are the biaiyl Stille and/or Suzuki couplings to form the biphenyl nucleus and the use of Mitsunobu chemistry to attach the variable side chains (Fig. 2). The illustrated route utilizes a solution-based diaryl coupling followed by on-resin Mitsunobu reactions. Although the diaiyl coupling proceeds on solid phase, this group s desire to maximize resin loading prompted them to implement the former route. 

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