Bi aryls

Ester exchange of bis-alkyl or bis-aryl carbonates of dihydroxy compounds with themselves or with other dihydroxy compound. 

Installation of a different side chain completely alters the pharmacological profile leading to a new class of muscle relaxants. The synthesis begins with copper(II)-promoted di-azonium coupling between furfural (j ) and 3,4-dichlorobenzene-diazonium chloride (15) to give bi aryl aldehyde Next, condensation with 1-aminohydantoin produces the muscle relaxant clodanolene (17). ... 

Quazepam (88) has a highly fluorinated sidechain so as to make this tranquilizer resistant to dealkylation. It also incorporates a lipid-solubilizing 2-thione moiety. The synthesis begins with bi aryl ketone derivative by ] -al kylation with 2,2,2-trifluoroethyltriclate to give 86. 

The heavy alkaline earth metals Ca, Sr, and Ba react with 2 equivalents of NJ -bis(2,6-diisopropylphenyl)formamidine in the presence of bis(pentafluorophenyl)-mercury to afford the bis(formamidinato) species as THF adducts in good to moderate yield (Scheme 23). When the same reactions are carried out in a 1 1 molar ratio, N-p-tetrafluorophenyl-N,N -bis(2,6-diisopropylphenyl)formamidine is isolated as the sole product in all cases (Scheme 23). Other substituted N -bis(aryl)formamidinate complexes of the heavy alkaline earth metals were synthesized accordingly. ... 

AstraZeneca has filed a patent application on novel bis-aryl compounds as CB1/CB2 agonists that lack CNS penetration and thus avoid the unwanted side effects associated with activation of central CBi receptors [210]. Over 100 compounds are specifically claimed e.g. (321). Compounds were tested in receptor binding assays using human CBi and CB2 receptor preparations. Respective K values were in the ranges 50-5,000 and 15-2,800 nM, although no specific data were presented. 

Having demonstrated a practical and reliable method to access 2-arylpyrrolidines in high enantioselectivity, we felt that a noteworthy extension of this methodology would lie in its application to bis-arylated products 27, providing a rapid and efficient approach to enantiopure C2-symmetric 2,5-diarylpyrrolidines, which have been identified as valuable chiral auxiliaries and chiral ligand manifolds [29]. Towards this end, substrate 26a was subjected to the standard arylation conditions, which produced 2,5-diphenyl-N-Boc-pyrrolidine 27 in a 96 4 diastereomeric ratio, and 57% isolated yield (s-BuIi/TMEDA produced 27 in lower d.r. (66 34) and yield (42%)), as depicted in Scheme 8.13. 

Bis(aryl)cobalt(II) compounds have been prepared by reaction of R MgX (where R = C6H6 Cl n = 2-4) with Co(PR3)2Cl2.203 They undergo both thermally and oxidatively induced decomposition, with the corresponding biphenyl a product. The reactions of alkyl-cobalt complexes have been reviewed recently, and include thermolysis, photolysis, oxidation, and reduction reactions.25 Homolysis of the Co—C bond is a feature of reactions. 

The bis-aryl hydrazone bond formed by this reaction is stable in aqueous solution over a broad pH range (pH 2-11) and under elevated temperature conditions (up to 94°C) (Solulink web site). 

Figure 18.15 NHS-chromogenic-PEG3-biotin contains an amine-reactive NHS ester that can be used to label biomolecules through an amide linkage. The chromogenic bis-aryl hydrazone group within the spacer arm of the reagent allows the degree of biotinylation to be quantified by measuring its absorbance at 354 nm. The compound also contains a hydrophilic PEG spacer, which provides greater water solubility.

Scheme 6.30 Domino Sonogashira sequence for the synthesis of bis(aryl)-alkynes.

The oxidation of aromatic aldoximes with ceric ammonium nitrate produces nitrile oxides which undergo subsequent cycloaddition to nitriles to produce 1,2,4-oxadiazoles (Equation 47) <1997PJC1093>. The anodic oxidation of aromatic aldoximes in the presence of acetonitrile has been reported to give low yields of either 3-aryl-5-methyl-1,2,4-oxadiazoles (2-25%) or 3,5-bis-aryl-l,2,4-oxadiazoles (6-28%), although the synthetic utility of this route is limited by competitive deoximation to the carbonyl being the major reaction pathway <1997MI3509>. 

Numerous modifications to the bis(aryl)-a-diimine ligand motif have been reported, especially in the patent literature. The review by Ittel includes an index of diimine and related ligands in proprietary publications up to the year 2000 [26]. Instead, this discussion will focus on academic reports of Ni(II) and Pd(II) polymerization catalysts bearing a-diimine or other closely related chelating neutral nitrogen ligands. 

The second type of porphyrin electrosynthesis discussed in this paper is controlled potential electrooxidation of a-bonded bis-alkyl or bis-aryl porphyrins of Ge(lV) and Si(IV). This electrooxidation results in formation of a-bonded mono-alkyl or mono-aryl complexes which can be isolated and characterized in situ. Again, cyclic voltammetry can be coupled with this method and will lead to an understanding of the various reaction pathways involved in the electrosynthesis. 

Germanium Porphyrins. The electrosynthesis of a-bonded mono-alkyl or mono-aryl germanium porphyrins involves the conversion of (P)Ge(R)2 to (P)Ge(R)X where X is an anionic ligand. A standard Grignard reaction between (P)Ge(Cl)2 and RMgX leads to the o-bonded bis-alkyl or bis-aryl complexes, (P)Gp(R)2. These complexes were initially synthesized as lH IWR shift reagents(28,29). However, almost no reactivity of these species was reported until several years later when it was shown that the... 

Miura s group carried out a heteroaryl Heck reaction of bromobenzene and 1-methylimidazole and isolated both mono-arylation (53%) and bis-arylation products [45], In accord with Ohta s observation, the first arylation took place at the electron-rich C(5) and the second arylation occurred at the more electron-poor C(2). 

Although the heteroaryl Heck reactions of chloropyrazines with pyrrole itself were low-yielding for both mono- and bis-arylation products, better yields were obtained for N-phenylsulfonylpyrrole. Bulkier alkyl substituents on the pyrazine ring promoted the formation of C(3)-substituted pyrroles. The C(3)-substituted pyrrole 64 was the major product (62%) for the coupling of 1 and Al-phenylsulfonylpyrrole, while C(2)-substituted pyrrole 63- was a minor product (15%). 

Spiro-lactarn 131 was formed by reaction of A/W -bis(aryl)tetrahydropyrrolo[2,l-c][l,4]oxazine-3,4-diylidenamines 130 with CO and ethylene in the presence of catalytic amounts of Ru3(CO)i2. The reaction (Equation 2), a formal [2+2+1] cycloaddition, <2001CC593>, is highly stereoselective and the conditions have been studied in detail <2003JM015>. 

The B-group vitamin, nicotinic acid (259), was irradiated with low-intensity light at 254 nm. In aqueous solution without buffer, the bi-aryl (260) was obtained, presumably via decarboxylation to give the pyridyl anion which would attack position 6 of nicotinic acid. In aqueous acid, the substrate was photo-hydroxylated to give 2-hydroxynicotinic acid (40%). Clearly, only the cationic form was sufficiently activated for position 2 to be attacked by the solvent. Nicotinamide under the same conditions was also converted to the 2-hydroxy derivative, but the reaction was slower [161]. 

Interestingly, bis-aryl-substituted co-polymers showed unusual substitution position-dependent and chiral mole frac-... 

Other applications might involve the synthesis of substituted alkylarenes useful as liquid crystalline materials. Liquid crystalline materials often contain bi-aryls or cyclohexylaryls and these can also made via one of the coupling reactions discussed above. 

Cyanamides - Cyanamides also represent a class of materials where reactive oligomers have been prepared. A representative example of the type of modification done to cyanamides to moderate the initial reaction to obtain linear soluble melt-processable oligomers 1s shown in Eq. 2. A bis(aryl sulfonyl cyanamide) was initially reacted with two moles of a bis (cyanamide) to yield an oligomeric mixture (ideally represented in Eq. 2 as a simple compound). These fire-resistant materials have shown promising properties as composite resin matrices (6). 

To date, the organometallic chemistry of copper, in terms of isolation and structural characterization of compounds, is essentially limited to the Cu(I) oxidation state. Only a very few examples of other oxidation states are known. The older literature offers a reported synthetic procedure for the synthesis of bis(aryl)copper(II) compounds [33, 34] (see Scheme 1.2), but this result has never been reproduced by others. 

Palladium-catalyzed intramolecular cross-coupling reaction of bis-aryl halides using ditin reagents. 

Plumbene-NHC complex 36 is generated by the reaction of an NHC with a bis(aryl)-lead(II) compound. The NHC-silylene adduct 37 also features a long C-Si bond with significant Si polarity. Pentacoordinated silicon(lV) and... 

Benzamides constitute a fourth dass of HDAC inhibitors. One example, MS-275, is a phenylenediamine derivative that exhibits robust HDAC inhibition in patients with advanced myeloid leukemia as well as refractory solid tumors or lymphoma in Phase I studies [72]. MS-275 is currently in Phase II trials. In a recent study aimed at optimizing the benzamide scaffold, several bis-(aryl) type analogs were synthesized and evaluated for their activity against a panel of HDACs [85]. Moradei et al. found that a thienyl substitution para to the free amino group in the phenylenediamine core rendered inhibitors specific for HDACsl, 2 with potency superior to that of MS-275. Isoform-specific inhibitors should aid in dissecting the roles of HDACs in normal cellular fundioning and cancer. 

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