Subject Homology

One of the most sensitive tests of the dependence of chemical reactivity on the size of the reacting molecules is the comparison of the rates of reaction for compounds which are members of a homologous series with different chain lengths. Studies by Flory and others on the rates of esterification and saponification of esters were the first investigations conducted to clarify the dependence of reactivity on molecular size. The rate constants for these reactions are observed to converge quite rapidly to a constant value which is independent of molecular size, after an initial dependence on molecular size for small molecules. The effect is reminiscent of the discussion on the uniqueness of end groups in connection with Example 1.1. In the esterification of carboxylic acids, for example, the rate constants are different for acetic, propionic, and butyric acids, but constant for carboxyUc acids with 4-18 carbon atoms. This observation on nonpolymeric compounds has been generalized to apply to polymerization reactions as well. The latter are subject to several complications which are not involved in the study of simple model compounds, but when these complications are properly considered, the independence of reactivity on molecular size has been repeatedly verified. 

The ability of C to catenate (i.e. to form bonds to itself in compounds) is nowhere better illustrated than in the compounds it forms with H. Hydrocarbons occur in great variety in petroleum deposits and elsewhere, and form various homologous series in which the C atoms are linked into chains, branched chains and rings. The study of these compounds and their derivatives forms the subject of organic chemistry and is fully discussed in the many textbooks and treatises on that subject. The matter is further considered on p. 374 in relation to the much smaller ability of other Group 14 elements to form such catenated compounds. Methane, CH4, is the archetype of tetrahedral coordination in molecular compounds some of its properties are listed in Table 8.4 where they are compared with those of the... 

One of the features of this subject which hitherto has been regarded as mysterious, is that in a homologous series of drugs some members may not only fail to produce the action typical of the series but may even antagonize the action... 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The cyclization of the homologous epoxide 36 under acidic conditions was also investigated (Table 9.5) [110]. As would be expected, compound 36a reacted by a 6-exo cyclization to give tetrahydropyran 38a (Entry 1). The a, 3-unsaturated hydroxy epoxide 36b gave a 1 3.5 mixture of oxepane 37b and tetrahydropyran 38b (Entry 2). Subjection of 36c and 36d, which both contain more electron-rich 71-systems, to the reaction conditions resulted in preferential 7-endo cyclization to give 37c and 37d, thus confirming the powerful regiodirecting effect of the vinyl moiety (Entries 3 and 4). 

It is well estabhshed that sulfur compounds as well as elemental sulfur have the tendency to form long chain molecules. All of these substances can be regarded as derivatives of the hydrogen polysulfanes (or polysulfanes) H2S . Polysulfanes form a long series of homologous chain-like molecules since the number n can assume any value. S-S and S-H bonds are frequently found in chemical and biological systems. Thus, polysulfanes have been the subject of numerous experimental and theoretical studies (for a recent review, see [15]). 

Fractions rejected by 1.0 KDa (C>i) and permeated through 0.5 KDa (C0 5) membranes were also subjected to TLC analysis. In Figure 3 are reported the values relevant to the various spots detected in the two samples as a function of an arbitrary polymerisation degree (DP). The good linear correlation between these parameters allows to hypothesise a difference of one monomer units between the subsequent spots [32]. Consequently, C0.5 would correspond to the monomer, Cj to an homologous series fi om the monomer to the hexamer. 

The substitution of CO in 2 by PF3 was recently the subject of an intensive investigation [47], that was followed by a similar study of the Mn-homolog [55], The authors investigated the substitutions by means of GC-MS, GC-IR and 19F-NMR. Assuming the composition [Tc2(CO)x(PF3)(i0 X)], there are 77 possible stereoisomers of which 24 could be assigned unambiguously, especially for x= 1, 2, 3. As was expected from the higher rc-density in the axial positions, substitution at these two positions was found to be preferred. 

Formation of the methyl-rhodium complex is analogous to the formation of CH3-C(C0)4 from CH30H2 arid Co(C0K as proposed by Wender. The difference here is that the nature of the active rhodium species is not known. Under the present conditions,homologation does not occur because CO is not present however, addition of the methyl-rhodium species to benzaldehyde must occur as shown in (19), metal adds to the oxygen. The product in (19) is then subject to acid catalyzed etherification to obtain the methyl ether. 

After clavulanic acid, the penicillanic acid derivatives (particularly the corresponding sulfone analogs) have been the subject of intense research in the -lactamase inhibitor area. From this extensive investigation, two compounds (sulbactam and tazobactam) from this class have been successfully introduced into clinical use. The penicillanic acid sulfones are /3-laclamasc inhibitors that are quite homologous to clavulanate in both their mechanism of action and in the spectrum of -lactamases susceptible to their action. The first notable success in this field was the discovery of sulbactam 7 (Fig. 7), which was reported by Pfizer chemists in 1978 and shown to possess potent inhibitory activity, principally for class A //-lactamases. It had greater affinity for class C types than clavulanate. From careful comparison of its structure to clavulanate, a rational basis for the similarities between the two is apparent. Both lack a C-6 substituent. Since the absence (or presence) of this substituent is an important, but not exclusive, factor in //-lactamase recogni-... 

Lengthening of the side chain of DMT by a single methylene group produces N,N-dimethylhomotryptamine (DMHT 76, R = H, n = 3), which produced hyperthermia when administered to rabbits (7,232) but was found to be inactive in man (235). Intravenous administration of 5 and 10 mg and intramuscular injection of 20 to 70 mg DMHT was without psychologic effect in 10 human subjects (235). Additional studies on DMHT homologs (i.e., 76, n = 4-10) did not show any interesting activity (7,232). 

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