Size of the alkyl group

Whereas introducing a thiol moiety at C-7 markedly reduced the antibacterial activity relative to lincomycin (79), the 7(3)-7-deoxy-7-alkylthiolincomycins exhibited considerably enhanced antibacterial activity without apparent regard for the size of the alkyl group (80—82). A marked increase in gram-negative activity was shown when the 7(3)-substituent contained a 2- or 3-hydroxy or amino group, but this activity was insufficient to be effective in infected mice (83—85). 

Porcine liver esterase (PLE) gives excellent enantioselectivity with both dimethyl 3-methylglutarate [19013-37-7] (lb) and malonate (2b) diester. It is apparent from Table 1 that the enzyme s selectivity strongly depends on the size of the alkyl group in the 2-position. The hydrolysis of ethyl derivative (2c) gives the S-enantiomer with 75% ee whereas the hydrolysis of heptyl derivative (2d) results in the R-monoester with 90% ee. Chymotrypsin [9004-07-3] (CT) does not discriminate glutarates that have small substituents in the 3-position well. However, when hydroxyl is replaced by the much bulkier benzyl derivative (Ic), enantioselectivity improves significantly. 

Alkyldithio carbamates are prepared from the acid chloride (Et N, EtOAc, 0°) and amino acid, either free or as the O-silyl derivatives (70-88% yield). The N- i-propyldithio) carbamate has been used in the protection of proline during peptide synthesis. Alkyldithio carbamates can be cleaved with thiols, NaOH, Ph P/TsOH. They are stable to acid. Cleavage rates are a function of the size of the alkyl group as illustrated in the table below. 

When larger alicj i groups are substituted for methyl, the mole fraction of the s-cis form progressively increases as the size of the alkyl group increases. ... 

With increasing alcohol concentration non-bulk electrostatic contributions become relevant. Because these non-bulk electrostatic contributions depend on the concentration of the cosolvent as well on the size of the alkyl-group, one can conclude that there is a relation to the smaller free energy necessary for exposing hydrophobic surfaces to the medium. It yields ... 

Further, for studying the role of pH and salt concentrations on bulk-electrostatic and non-bulk electrostatic contributions the same approach was made to experiments on the influence of the alcohols mentioned above on the oxygen affinity at various KC1 concentrations and pH-values 144,146). The results obtained indicate that at a low alcohol concentration the bulk-electrostatic contributions are dominant and that with increasing size of the alkyl group, alcohol and KC1 concentration, the nonbulk electrostatic, hydrophobic contributions increase. Recent results of kinetic measurements of 02 release show that cosolvents such as alcohols and formamide influence mainly the allosteric parameter L, i.e. -the equilibrium between T and R conformation and that the separation of the alcohol effects into bulk-electrostatic and hydrophobic (non-bulk electrostatic) contributions is justified. 

The ratio of ortho- to the meta- and /faru-products of monoalkylbenzenes with 1 decreased as the size of the substituents on benzene ring increased. No ortho-alkylation product was found in the case of i-propylbenzene due to the sterie interaction between /-propyl and the incoming allyl groups. Sterie hindrance arising from the size of the alkyl groups at ortho positions of the substituted benzenes appeared to be the principal cause of the differences in isomer product ratio." " ... 

When re-alkyl ethynyl ketones were tested as the substrate of LBADH, the preferred stereochemistry and optical purity of the resulting propargylic alcohol were dependent upon the size of the alkyl group (Figure 7.26) [71]. 

The hydrolysis rate of organosilanes is a strong function of the size of the alkyl group and steric hindrance. Actually, however, these reactions never result in the formation of pure silica oxides, and it is precisely the fact that m A 0 and that a large number of unreacted silanol groups exist at the material s surface that gives rise to the impressive variety of chemical applications of doped silica xerogels.2... 

Association trends also reflect for the most part increasing solvation with decreasing size (Table 4). Tetraalkylammonium salts become less associated as the size of the alkyl group becomes larger, an expected trend for these relative-... 

Three main structural sub-groups can be recognised alkylaluminium dihalides, dialkylaluminium halides, and trialkyldialuminium trihalides (equimolar complexes of a trialkylaluminium and an aluminium trihalide). While this is generally a very reactive group of compounds, similar in reactivity to trialkylaluminium compounds, increase in size of the alkyl groups present and in the degree of halogen substitution tends to reduce pyrophoricity. 

Despite their importance in many pharmacological uses and potential applications, solubilities of hydroxypyranones, hydroxypyridinones, and their complexes have not been extensively and systematically investigated and established. This situation contrasts sharply with that for partition coefficients, as will become apparent in the following section. The solubility of maltol in water is approximately 0.1moldm , of ethyl maltol 0.13 mol dm, at 298 K. 1,2-Alkyl-3-hydroxy-4-pyridinones show the expected decrease in water-solubility as the sizes of the alkyl groups increase solubilities - in water at 298 K - of l-aryl-2-methyl-3-hydroxy-4-pyridinones decrease from 9 X 10 mol dm for the 1-phenyl compound through 6 x lO- moldm for l-(4 -tolyl) to 6 x 10 mol dm for l-(4 -re-hexyl-phenyl) (37). 

Solubility in water Ethers are usually soluble in water. The solubility of an ether decreases as the size of the alkyl groups increases. 

The decrease in hydrogenation rate with increasing size of the alkyl group (Table VI) (93-96) can be correlated by the Taft equation. However, the correlation of the data by Smith and Pennekamp (93) (series 70) using the polar parameter Taft equation is applied that also includes steric constants. Similarly, Kieboom (34) has discussed Yoshida s correlation of series 73 based on main conclusion has been that the data do not allow a clear distinction between steric and polar effects. It seems that both operate in the same direction. Series 72 and 73, in which the rate data have been separated into the rate constants and adsorption coefficients, show opposite trends with the latter parameter. A similar problem has been encountered by Volter, Hermann, and Heise (100) and by Najemnik and Zdrazil (103) in the series of methylbenzenes (Table VII) and is discussed in this connection. 

The size of the alkyl groups in the haloalkane is Important. This is known as a steric effect. You will recall that, in the mechanism, the nucleophile attacks the carbon atom of the C-X bond from the side opposite to the halogen atom. In the case of a tertiary haloalkane, attack from that side is likely to be sterlcally hindered because three bulky alkyl groups will limit access to the atom. Hence tertiary haloalkanes are unlikely to react with nucleophiles via an Sj. 2 mechanism. Primary haloalkanes, on the other hand, have no more than one alkyl group attached to the halogen-bearing carbon atom and so access to the atom will be much easier. This suggests that primary haloalkanes are most likely to react with nucleophiles via an S. j2 mechanism. 

Uracil and thymine are both reported to have electroshock anticonvulsant activity [371]. A series of 5- and 6-alkyl derivatives was prepared [373] and tested for electroshock as well as for metrazole protection [374]. It was found that most compounds of this type were active in the electroshock test. There is a trend toward increased activity with increased size of the alkyl groups, and introduction of 1,3-dimethyl substituents is also of benefit. Against metrazole-induced shock, however, there are no obvious structure-activity relationships. 

SOLUBILITY MEASUREMENT. The solubilties of the extracts in liquid benzene at room temperature are shown in Table HI. Solubility increases with the size of the alkyl group and appears to reach a limit of 77% soluble. 

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