Steric Effects and Hydrogen Bonding

While monosubstituted alkenes usually react with high regioselectivity, it is not true for disubstituted alkenes. Formation of mixtures of type 163 and 164 (equation 105) has been observed in most cases when unsymmetrical alkenes bearing two different substituents possess similar stereoelectronic properties. In general, regioselectivity is controlled by a combination of HOMO-LUMO interactions, steric effects and hydrogen bonding between suitable substituents in both alkene and nitrone molecules . ... 

The branching angles chemical nature (geometry) of the branch juncture, whereas the rotational angles secondary-structure parameters such as steric effects and hydrogen bonding. 

S. J. Leach, G. Nemethy, and H. A. Scheraga, Biopolymers, 4, 887 (1966). Intramolecular Steric Effects and Hydrogen Bonding in Regular Conformations of Polyamino Acids. 

Additional experimental evidence is sparse [78, 79]. The geometric changes are consistent with an enhanced anomeric effect, not a reverse one [68, 80] Molecular orbital calculations are not conclusive because it is difficult to separate the RAE from steric effects and hydrogen bonding, which also favor the equatorial con-former [70, 81-84]. 

Leach, S. J., N methy, G. Scheraga, H. A. (1966b). Intramolecular steric effects and hydrogen bonding in regular conformations of polyamino acids. Biopolymers, 4, 887. 

Klein and Kdnig," for example, have reported the synthesis of a sulfonamide substituted 1,2-aryldiyne 111, where the sulfonamide group, being a cr-acceptor, should facilitate the Bergman cycloaromatization. However, as reported by Zaleski for a series of l,S-bis substituted oct-4-ene-2,6-diyne derivatives 113, steric hindrance and hydrogen bond formation between the terminal substituents can influence the temperature of the cyclization, and therefore the reactivity of the sulfonamide compound 111 is comparable with the one of the unsubstituted analog 112, since the electron withdrawing effect of the substituent is compensated by its steric hindrance (Scheme 19.30). 

Brigghente IMC, Vottero LR, Terenzani A, Yunes RA (1991) Addition of hydroxylamine to cyclohexanone and bicyclic ketones. Steric, electronic and hydrogen bonding effects on the general mechanism of addition of amines to carbonyl compounds. J Phys Org Chem 4 107... 

A series of new chiral furan derivatives has also been published demonstrating the utility of both the CB-DM and CB-RSP to separate based on steric bulk in simple methanol/water mixtures [12], This technique of steric repulsion as a mechanism was also demonstrated for the separation of 16 racemic dihydrofuroflavones with a similar complementary effect for the CB-DM and CB-RSP [13], Another example of this useful combination of steric bulk and hydrogen bonding mechanism for the CB-RSP can be found in the publication cited for the separation of 12 chiral dihydrobenzofurans [14]. 

The solubility of a compound is thus affected by many factors the state of the solute, the relative aromatic and aliphatic degree of the molecules, the size and shape of the molecules, the polarity of the molecule, steric effects, and the ability of some groups to participate in hydrogen bonding. In order to predict solubility accurately, all these factors correlated with solubility should be represented numerically by descriptors derived from the structure of the molecule or from experimental observations. 

Prototropic tautomerism differs from all other types (methyltropy, metallotropy, acylotropy, halogenotropy, etc.) because the proton is very small, and therefore insensitive to steric effects, and also that it forms hydrogen bonds (HBs), which can considerably affect both the equilibrium and the rate of the process. 

Figure 5.3 The effect of hydrogen bonding and steric hindrance on the difference between liposome-water and octanol-water partition coefficients 8 increased H-bond donor strength and decreased steric hindrance favor membrane partitioning in the substituted phenols [381]. [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

---