Substituent selection

Electron-donor and electron-acceptor substituents selectively interact with different ring orbitals. Compare the HOMO and LUMO of azobenzene with the corresponding orbitals of the two substituted molecules. Which orbitals show signficant substituent contributions What are the nature of these contributions, bonding or antibonding Try to relate this to the effect which the substituents have on orbital energies and on the HOMO-LUMO gap in azobenzene. 

Substrate Small Substituent Large Substituent Selectivity (E)... 

To retain a side-chain substituent, selective methods of oxidation are required. For example, 4-methylbenzoic acid can be prepared from l-(4-methylphenyl)-ethanone by the haloform reaction (Section 17-2B) ... 

Derivatives of a-diaminodihydroxyanthraquinones are the most important disperse dyes with respect to shade and affinity. The dye properties may be optimized by introducing suitable substituents, selecting the positions of the isomers, and blending. Some of these properties can be illustrated with the three basic structures 9-11. 

Ci 6 alkyl is a carbon chain of between 1 and 6 carbon atoms in length, wherein said carbon chain may be optionally unsaturated, thus including alkenes and alkynes. Said Ci 6 alkyl group may be optionally substituted with from 1-3 substituents, wherein said substituents are selected from halogen, hydroxyl, nitro, cyano, and phenyl (wherein said phenyl is optionally substituted with from 1-3 substituents selected independently from the group consisting of halogen, hydroxyl, cyano and nitro). 

As a result of the limited configurational stability of optically active organotin compounds, in which the chirality is on the tin atom, most advances in enantioselective free-radical reductions involve organostannanes where the elements of chirality are contained in the organic substituents. Selected... 

The Hantzsch synthesis of thiazoles is an excellent method for the synthesis of simple thiazoles, however for some substituted examples low yields have been reported as a result of dehalogenation of the a-haloketone. An alternative method for the synthesis of highly substituted thiazoles has been reported, thus starting from the 2-bromo-5-chlorothiazole 76 it was possible to introduce substituents selectively at the 2-position by a palladium-catalysed cross coupling reaction to give 77 (74-92%). In order to introduce a substituent into the 5-position,... 

Without the cis substituent, selectivity is much lower m-CPBA 0... 

Borth, D.M. and McKay, R.J. (1985). A Difficulty Information Approach to Substituent Selection in QSAR Studies. Technometrics, 27,25-35. 

A large number of substituent descriptors have been reported in the literature. In order to use this information for substituent selection, appropriate statistical methods may be used. Pattern recognition or data reduction techniques, such as PCA or CA are good choices. As explained in Section III.B.3. in more detail, PCA consists of condensing the information in a data table into a few new descriptors made of linear combinations of the original ones. These new descriptors are called PCs or latent variables. This technique has been applied to define new descriptors for amino acids, as well as for aromatic or aliphatic substituents, which are called principal properties (PPs). These PPs can be used in FD methods or as variables in QSAR analysis. ... 

Reduction of anilines to cyclohexylamines over RuOj works successfully on a series of nuclear substituted substrates, at 90-125°C, 8 X 10 kPa, in alcohols or without solvent". Yields of 92% are obtained in the preparation of diamines such as bis(4-aminocyclohexyl) methane, the product being mostly cis,cis and cis,trans isomers . Phenylenediamines are reduced to the 1,3-diamine (91%) or to the 1,4-diamine (88%) over ruthenium-on-alumina in ethanol. The c/j-isomer predominates (70-84%) in a number of solvents and over a range of experimental conditions ". Synthetic advantages can be taken from some side reactions. Hydrogenation of 3,4-diaminobenzoic acid can lead to a mixture of bicyclic lactams that lack an amino substituent . Selective hydrogenation of trisubstituted aniline 9 affords lactame 10, an intermediate in the total synthesis of ibogamine. ... 

Topliss tree The Topliss tree is an empirical decision scheme for a stepwise aromatic substituent selection and lead optimization that is guided by the supposed influence on potency due to the hydrophobic, electronic, and steric effects of the substituents. 

In order to obtain further information on the magnitude of the overall reaction volume and the location of the transition state along the reaction coordinate, a series of intermolecular electron-transfer reactions of cyt c with pentaammineruthenium complexes was studied, where the sixth ligand on the ruthenium complex was selected in such a way that the overall driving force was low enough so that the reaction kinetics could be studied in both directions [64, 65]. The substituents selected were isonicotinamide (isn), 4-ethylpyridine (etpy), pyridine (py), and 3,5-lutidine (lut). The overall reaction can be formulated as shown in Eq. (1.9). 

A is a bivalent radical selected from (1), (2), and (3) and R1 and R3 are the same or different and each is a substituent selected from H, Cl, Q- alkyl, methoxy, ethoxy, and sulphonic acid radical or a salt thereof, sulphonamide radical, and Q- alkyl-substituted sulphonamide radical. 

Fig. 22.11 Optimal substituent selection of soluble COMT inhibitors by PLS.

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