Steric hindrance methyl groups

In order to increase the self-catalytic activity, high MW aminic polyols were created based on polyamines having one or two nitrogen atoms and low steric hindrance methyl groups (-N-CH3 groups), such as [149-151] ... 

Electronically, these molecules differ little, so this is clearly about steric hindrance. A group at the 2-position of cyclohexanone will interfere sterically with the formation of the cyanohydrin. A methyl group is relatively small, but a ferf-butyl group has a much larger effect. At the 4-position, the tert-butyl group is too far away to exert any steric influence on the equilibrium, so the result is the same as for cyclohexanone itself. 

In this case the relationship between stability and stereochemistry is easily explained on the basis of van der Waals strain The methyl groups on the same side of the ring m cis 1 2 dimethylcyclopropane crowd each other and increase the potential energy of this stereoisomer Steric hindrance between methyl groups is absent m trans 1 2 dimethylcyclopropane... 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

The methyl groups direct the entering group primarily to the ortho and para positions (Table 3). The preferred site of attack by an electrophile on pseudocumene and hemimellitene is shown as follows (13) however, steric hindrance can cause a shift such as a / fX butylation of hemimellitene predominandy at the 5-position. Mesitylene, all three tetramethylbenzenes, and pentamethylbenzene can only form one mono- and one disubstituted isomer (except pentamethylbenzene). Hence, high purity derivatives are possible. 

The basicities of the parent azole systems in water are shown in Table 1. When both heteroatoms are nitrogen, the mesomeric effect predominates when the heteroatoms are in the 1,3-positions, whereas the inductive effect predominates when they are in the 1,2-positions. The predominance of the mesomeric effect is illustrated by the pK value of imidazole (82 Z = NH), which is 7.0, whereas that of pyrazole (83 Z = NH) is 2.5 cf. pyridine, 5.2). An fV-methyl group is base-strengthening in imidazole, but base-weakening in pyrazole, probably because of steric hindrance to hydration. When the second heteroatom is oxygen or sulfur the inductive, base-weakening effect increases the pK of thiazole (82 Z = S) is 3.5 and that of isoxazole (83 Z = 0) is 1.3. 

Figure 4.2. Rotational-energy barriers as a function of substitution. Tbe small barrier ( 2kcal) in ethane (a) is lowered even further ( O.Skcal) if three bonds are tied back by replacing three hydrogen atoms of a methyl group by a triple-bonded carbon, as in methylacetylene (b). The barrier is raised 4.2 kcal) when methyl groups replace the smaller hydrogen atoms, as in neopentane (c). Dipole forces raise the barrier further ( 15 kcal) in methylsuccinic acid (d) (cf. Figure 4.3). Steric hindrance is responsible for the high barrier (> 15 kcal) in the diphenyl derivative (e). (After...

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

The 13-ethyl-17-ketones, i.e., (63), have been found to be considerably less reactive than their 13-methyl counterparts towards acetylenic nucleophiles. The difference is attributed to the additional steric hindrance provided by the ethyl group. An attempt to introduce an ethynyl group into mc- 2>-isopropyl-3-methoxygona-l,3,5(10)-trien-17-one was unsuccessful even in ethylenediamine at 50°. However ethynylation of rac-13-isopropyl-3-methoxygona-1,3,5(10),8(14)-tetraen-17-one proceeded smoothly at room temperature to afford the 17a-ethynyl compound in 60% yield. ... 

In cases where steric hindrance at the 17-ketone is increased by alkyl groups other than methyl at C-13, lithium acetylide in aniline or dimethylacetamide is more satisfactory than conventional methods. ... 

In addition to the intramolecular effects, steric factors are of considerable influence. The most usual one consists of steric hindrance to attack on the lactam nitrogen atom. Certain examples of this will be given. By comparison with uracil, it would be expected that uric acid (10) would be iV-methylated in the pyrimidine ring, but that in the imidazole ring 0-methylation should also be possible. However, the experiments of Biltz and Max show that all uric acid derivatives which carry a hydrogen atom in the 9-position are converted by ethereal diazomethane into l,3,7-trimethyl-8-methoxyxanthine (11). The following are examples uric acid and its 1-methyl, 3-methyl, 7-methyl, 1,3-dimethyl, 1,7-dimethyI, 3,7-dimethyl, and 1,3,7-trimethyl derivatives. Uric acid derivatives which arc substituted by alkyl groups in the 3- and 9-positions (e.g., 3,9-dimethyl-, 1,3,9-trimethyl-, and 3,7,9-trimethyl-uric acid)do not react at all with diazomethane, possibly because of insufficient acidity. Uric acids which are alkylated... 

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