Di-substituted benzene derivatives

Manzo, R. H. and A. A. Ahumada. 1990. Effects of solvent medium on solubility. V Enthalpic and entropic contributions to the free energy changes of di-substituted benzene derivatives in enthanol water and enthanofcyclohexane mixtur fc. Pharm. Sci79 1109—1116. 

Kaiser, K.L.E., QSAR of acute toxicity of 1,4-di-substituted benzene derivatives and relationships with the acute toxicity of corresponding mono-substituted benzene derivatives, in QSAR in Environmental Toxicology — II, Kaiser, K.L.E., Ed., D. Reidel Publishing Company, Dordrecht, 1987, pp. 169-188. 

If we now proceed to consider those mono- and di-substituted benzene derivatives in which as a good approximation we may assume the existence of rotational symmetry, as is shown by the values of the depolarization factor of scattered light differing only slightly from the values for benzene, we have the following state of affairs. 

Table XCIX. Dipole Moments of Di-substituted Benzene Derivatives halogen derivatives...

The first deep-cavity cavitand to be synthesized was the 2.3-quinoxaline derivative 4 (Fig. 4). This second row of aromatic rings in this cavitand. and related cavitands formed by the condensation of resorcinarenes with 2,3-dichloropyrazines. is conformationally flexible. Thus, they exist in a range of conformers between the vaselike C4v form (shown) and a flat C21 form. These families of compounds were termed velcrands, because in the flat, "kite-like" form, they have a propensity to dimerize.When not binding themselves, these types of cal-itands also bind mono-" or di-substituted"benzene derivatives. 

QSAR OF ACUTE TOXICITY OF 1,4-DI-SUBSTITUTED BENZENE DERIVATIVES AND RELATIONSHIPS WITH THE ACUTE TOXICITY OF CORRESPONDING MONO-SUBSTITUTED BENZENE DERIVATIVES... 

In addition to the log P, other physico-chemical parameters were investigated as to their relationship with the observed toxicities of both the subgroups and the entire set of 1,4-di-substituted benzene derivatives. Parameters so used include w for each of the subset functional groups (R = NO2, NHj, Cl, OH, NMOj), and the substituents (X) molar refractivity (AMR), cTp, and field and resonance contributions, as listed by Hansch and Leo (1979). While some of the correlation coefficients improved and slightly lower s values were obtained, all these derived equations fail to satisfy the demand for an explanation of all the data with an acceptable standard error of, say, s = 0.3 to 0.4 log units. It can be concluded then, that one or more of the following conditions prevail ... 

Both equations 5 and 6 are statistically highly significant. However, their practical use for the prediction of toxicities of other 1,4-di-substituted benzene derivatives will be limited until the reasons for the existence of the outliers (group 2 type compounds) are known, and hence their a priori identification is possible. 

Among the di- substituted benzene derivatives, we find very often that the order of solubility lies in the order of the melting-points. This is illustrated in the solubilities of the following substituted benzoic acids. 

The first dataset consisted of 91 rigid compounds (mono- and di-substituted benzenes, polycyclic aromatic hydrocarbons, cyclic amides, and pyrazole and imidazole derivatives) selected from the WDI on the basis of a count of the number of rotatable bonds computed using TSAR none of the 91 structures had rotatable bonds. The structures are listed in Table 1 together with their experimental log Poct values, which cover a range from -2.17 to +6.5 the values were retrieved from the SRC web site (27). 

Ring fluorination is observed in reactions of protected aniline derivatives, with the ojp ratio of the products, e.g. 11-13, being dependent on the substituent 5 nitrobenzene is unreactive towards electrophilic substitution. The polymerization process may be studied by di-fluorobis(fluoroxy)methane reactions with variousfluoro-substituted benzene derivatives (hexa-... 

Abbreviations arene, i/6-benzene or substituted benzene derivative bipy, 2,2 -bipyridyl Bu, Bu", Bu, iso-, n-, or rerf-butyl COD, 1,5-cyclo-octadiene Cp, /5-C5H5 DAD, dimethyl-acetylene dicarboxylate dam, 1,2-bis(diphenylarsino)methane DBA, dibenzylideneacetone DMF, A. A -dimethylformamide dpe, l,2-bis(diphenylphosphino)ethane dpen, os-l,2-bis(di-phenylphosphino)ethylene dpm, 1,2-bis(diphenylphosphino)methane ESR, electron spin resonance F6-acac, hexafluoroacetylacetone FN, fumaronitrile MA, maleic anhydride Me, methyl MLCT, metal ligand charge transfer phen, 1,10-phenanthroline Pr , Pr", iso- or n-propyl py, pyridine RT, room temperature TCNE, tetracyanoethylene tetraphos, (Ph2PCH2CH2)jP THF, tctrahydrofuran Xylyl, 2,6-Me2C6H3. 

Only little has been reported on second-order hyperpolarizabilities yin two-di-mensionally conjugated molecules. Planar systems as e.g. phthalocyanines have been studied for two photon absorption which is proportional to the imaginary part of the nonlinearity y. For planar molecules with a three-fold symmetry, the importance of charge transfer from the periphery to the center of the molecule in order to realize large nonlinearities ywas reported [65]. Off-resonant DFWM experiments revealed promising third-order nonlinearities in two-dimensional phenylethynyl substituted benzene derivatives [66]. Recently, the advantage of two-dimensional conjugation to increase the values of the first-order hyperpolarizability p has also been pointed out [67-69]. 

The mono- and di-substituted benzenes, for which the relative swelling power (C as defined in Eq. 14) have been determined thus far, are listed in Tables 2-4. In every case the volume (S) of sorbed liquid per gram of polymer increased linearly with X1/3 as noted in Figs. 9-11, and the square of the correlation coefficient (r) to the line of best fit, determined by linear regression analysis of the set of six S-data points, was in every case r2 > 0.99, and q13 was equal to 1.84 0.09. The corresponding C and oc (calculated therefrom Eq. 15) are also collected in Tables 2-4. These data show clearly that the value a = 2.50 for benzene is greater than that for any benzene derivative listed therein. Any substituent in place of... 

Rule III chiefly applies to multi-substituted benzene derivatives. If we assume that the six carbon atoms in benzene are arranged so as to form a regular hexagon, the angle between the directions of the substituents is 6o° in the or Ao-position, 120° in the mp -position, and 180° in the /> m-position. If the two substituents have the group moments fx and /xg he moment of the di-substituted molecule is given by... 

In the nitrobenzonitriles, such resonant structures will be mutually suppressed and consequently no large deviations from the additivity rule occur, such as exist when the two groups are of opposite charge so that the resonance is augmented by additional valence bond structures. The dipole moment of />-nitrobenzonitrile is zero, of o-nitrobenzonitrile, 6 19, D and m-nitro-benzonitrile, 3-78, D. Similar behaviour is observed with the di-substituted halogen derivatives of benzene and with the phenylenediamines. 

Isomerism.— As all of the second group, in which substitution occurs in the side chain, considered as benzene derivatives, are mono-substituted benzenes, they do not exist in isomeric forms, and only one compound of each formula is known. The first group, however, in which halogen substitution occurs in the ring, are all poly-substitution products of benzene, since toluene itself is a mono-substituted benzene. Mono-chlor toluene is, therefore, a di-substituted benzene, and occurs in the three forms, as follows ... 

A [4 -t- 2]cycloaddition between enynes and 1,3-diynes, with the latter serving as the two-carbon component, results in substituted benzene derivatives. The adducts derived from l,4-di-t-butoxy-l,3-butadiyne are readily converted to coumaranones. ... 

Partial order can be used to relate molecules that are structurally similar, such as is the case with benzene derivatives, the partial ordering of which is illustrated in Figure 2.2. At the top of Figure 2.2 is benzene, which is followed by one mono-substituted benzene. Additional substitution gives three di-substituted benzenes as shown in the third row of the diagram. Adding another substituent results again... 

For dihydrodiols derived from substituted benzenes, the key to their significance lies in the availability of two adjacent chiral centers with an established absolute stereochemistry. The dihydrodiol from benzene is, of conrse, the meso compound, although enantiomers produced by subsequent reaction with a chiral reagent are readily separated. There are useful reviews containing nnmerous applications (Carless 1992 Ribbons et al. 1989), many of which involve, in addition, the nse of di-flnoro-, di-chloro-, or di-bromobenzene-2,3-dihydrodiols. 

The structural comparison (Fig. 3) with both the twofold tris(trimethylsilyl)methyl substituted acetylene and 1,4-benzene derivatives (Fig. 1) as well as with the literature data [6a] for hexa-kis(rm.butyl)disilane [6b] containing a SiSi bond elongated to 270 pm ( ), for the linear ( ) hexa-kis(rm.butyl)disiloxane [6c] or for di(tris(trimethylsilyl)silyl)zinc [6d] is based advantageously on a model in which the two substituent half-shells are separated along their central C3 axes by spacers of different lengths. 

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