Effects of substituent groups

As would be anticipated, the nature of substituent groups has a profound influence on the reactivity and polymerizability of an NCA. The rates of reaction between NCA and base molecules are affected by stereochemical and electronic factors further, in suitable circumstances, interactions between propagating species and side-chain groups may occur. 

Reactions between iV-carboxy-anhydrides and bases, NHR4CH2CONMe2 in nitrobenzene at 15°C 

A-Carboxy-anhydride Base R4 k (mole 1 sec ) Rates of addition on two sides of ring  

L-proline NCA is comparatively reactive. In part this may arise from strain in the molecule. However, the fused rings confer a saucer-like shape on the molecule and attack at C5 from the convex side should be relatively free from obstruction by substituents on the ring nitrogen and C4. This is probably the explanation of the comparatively fast reaction of L-proline NCA with Al-isopropylglycine dimethylamide (R4 = iPr), of which the rate coefficient is approximately 6000 times that of the corresponding reaction with N-methyl-DL-alanine NCA (R, = R3 = Me, R2 = H). 

The rates of addition of the bases on the two sides of the rings of various NCA s are summarized qualitatively in the right-hand portion of Table 2. 

---

Table 7.51 Effect of Substituent Groups on Alkyl Chemical Shifts 7.102...

Because nitration has been studied for a wide variety of aromatic compounds, it is a useful reaction with which to illustrate the directing effect of substituent groups. Table 10.3 presents some of the data. A variety of reaction conditions are represented, so direct comparison is not always valid, but the trends are nevertheless clear. It is important to remember that other electrophiles, while following the same qualitative trends, show large quantitative differences in position selectivity. 

Relative values of the rate constants are useful in themselves by measuring such values for the reactions of a series of compounds with the same reactant, one is able to determine the rank order of reactivity within the series. Such determinations are useful in the development of correlations of the effects of substituent groups on the... 

Table 4.3 The effect of substituent groups on fluorescence efficiency of naphthalene and its derivatives. Fluorescence quantum yields measured in fluid solution at room temperature...

The effect of substituent groupings upon the first ionization potential of, at least, the aliphatic aldehydes and ketones does not seem to provide clear evidence for a choice between loss of a 7r-electron from the C=0 double bond or one of the oxygen lone-pair electrons. Concordant data for the homologous series of aliphatic ketones have been obtained by... 

It is known that the effects of substituent groups on a diene or dienophile vary between different types of parents [23]. A function, r(Y), has been determined for several functional groups, with Y corresponding to their electron donating or withdrawing capability such that a reasonable estimate of the HOMO energy could be obtained by use of the equation [15] ... 

The effects of substituent groups in the reactions of the cationic heterocycles with nucleophiles are entirely as expected. Appropriately situated substituent groups which can function as leaving groups can be displaced (e.g. equation 41), and ANRORC reactions are very common (e.g. equations 42 and 43). The latter type of reaction is of particular... 

The effects of substituent groups in the benzo-fused ring on the ease of electrophilic aromatic substitution are essentially identical to those of the same substituent groups in benzene, so electron-donating groups facilitate reaction while electron-withdrawing groups... 

Structure and stability of the ions and the effects of substituent groups on that stability. 

EFFECTS OF SUBSTITUENT GROUPS ON THE FLUORESCENCE OF AROMATIC COMPOUNDS... 

A method using the Atomistic approach (Masuda, 1996) was published recently and claims an improved performance from consideration of solute SASA as well as proximity effects of substituent groups. Measured values for 500 solutes were taken as a test set, but just how substituent proximity was taken into account was not explained. For a set of 20 pharmaceuticals not in the original test set, five methods other than the SASA-scaled atomistic method were compared. Table 5.1 shows the statistical results for the best three methods. 

The structural aspects which determine the inherent capability of these acids to undergo ring closure, and which consequently control the course of the cyclization, are (a) the size of the ring formed (b) the reactivity of the aromatic nucleus, including the effect of substituent groups (c) steric considerations other than ring size. 

The behavior of pyridine, its i T-oxide, and its quaternary salts has been the subject of a number of recent theoretical treatments.1-4 The general conclusions will be summarized here to serve as a guideline on which to superimpose the effect of substituent groups. 

As previously described, the effect of substituent groups on the silyi function is an important factor in terms of determining the reaction course. Table 4 shows the ratio of the products in the Pummerer reaction using various SKAs.33 These results suggest that carbon-carbon bond formation preferentially occurs when using a small silyi function such as the trimethylsilyl function. This tendency was observed in another substrate which has asymmetric carbon at the (3-position of the sulfur atom (Table 5).33 Interestingly, the syn-selectivity of the rearrangement product... 

---