Substitution with Side-chains

Substitution with side-chains can have its disadvantages if the structural regio-regularity of the oligomer or polymer is not carefully controlled by the chemical 

Regioregular alkyl-substituted poly(thiophenes) [46, 47] and oligo(thiophenes) [48] have also been synthesized, in which the alkyl chains are always substituted to the same type of /3-carbon atom, thus producing predominantly head-to-tail interactions, as shown in Fig. 5b, and therefore reducing steric interactions between the alkyl chains. 

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Compounds in the vitamin K series are 2-methyl-l,4-napthoquinones, which are substituted with side chains at carbon 3. FhyUoquinone (Ki type) synthesized in plants and the menaquinones (K2 type) of bacterial origin are the two principal natural classes of vitamin K (Figure 30-6). The principal vitamin Ki (phyUoquinone) bears a saturated, phytol, 20-carbon side chain derived from 4 isoprenoid units this is the main K vitamin produced by plants and is tire major dietary form for humans. K2 shows greater vari-... 

The a-carbon of the oligocarbamate backbone, like that of peptides, is substituted with side chains containing a variety of functional groups. A further backbone modification and conformational restriction can be incorporated via N-acylation followed by reduction of the N-acyl nitrogen, yielding N-alkyl-oligocarbamates (Scheme 7.4) [28]. 

Aromatic hydrocarbons are of special commercial importance. The benzene ring structure, with six carbons and three double bonds, is the fundamental aromatic unit. This molecule can have one or more hydrogen substitutions with side chains, resulting in alkyl benzenes (e.g. the TEX in BTEX [benzene, toluene, ethylbenzene and xylene]) or two or more aromatic rings may be fused together to form polycyclic aromatic hydrocarbons (PAHs). 

Using 1,5-diynes as precursors to o-xylylenes, whidi then are trapped by Mej SiC2 SiMe, or trapped intramolecularly by using diynes substituted with side chains bearing potential dienophiles, polycyclic systems are generated in a one-pot reaction from acyclic starting materials (Funk and Vollhardt, 1976). 

Two-step 1,4 cycloaddition of enamines, such as was observed with methyl vinyl ketone, is not possible with acrylate or maleate esters. This is due to the fact that, following the initial simple substitution, no side-chain carbanion is available for nueleophilic attack on the a carbon of the iminium ion. Likewise two-step 1,3 eycloaddition, such as that found when alicyclic enamines were treated with acrolein, is impossible with acrylate or maleate esters because transfer of the amine moiety from the original enamine to the side chain to form a new enamine just prior to the final cyclization step is not possible. That is, the reaction between a seeondary amine and an ester does not produce an enamine. 

Data for other p-substituted benzene side-chain reactions are fitted by eq. (1) using the oj and Or values of Table I with widely varying precision measures. However, precision of fit comparable to that achieved for the eight basis set reactions of Table II is obtained (only) with recognizable analogs of the para BA type. Other reaction types are fitted generally with values of / SD/RMS greater by factors of two or more than the i>% level achieved by the para BA type (cf. subsequent Tables VII, IX, XII, XIV). 

The pioneering work on enantioselective ruthenium olefin metathesis was carried out by Grubbs and co-workers in 2001 [69] (Fig. 3.23). Catalysts 55a-b and 56a-b were designed and prepared from C -symmetric NHC hgands with a combination of chiral backbone and mono-ortfto-substituted aryl side chains, a motif that was expected to form a chiral environment around the metal centre. 

Subsequently, these catalysts were evaluated in the enantioselective desymmetri-sation of achiral trienes, and three distinct trends in catalyst selectivity were found. Firstly, catalysts 56a-b with two phenyl moieties on the backbone of the A -heterocycle exhibited higher enantioselectivity than those with a fused cyclohexyl group as the backbone 55a-b. Secondly, mono-ort/io-substituted aryl side chains induced greater enantioselectivity than symmetrical mesityl wing tips. Thirdly, changing the halide ligands from Cl to I" increased the enantioselectivity. As a result, catalyst 56b turned out to be the most effective. For example, 56b in the presence of Nal was able to promote the desymmetrisation of 57 to give chiral dihydrofuran 58 in up to 82% conversion and 90% ee (Scheme 3.3). 

Rhodococcus sp. AJ270 was applied to the transformation of a number of racemic cis- and traray-3-aryl-2-methyloxiranecarbonitriles (Figure 8.7). In all cases, the NHase activity proceeded very rapidly and with poor enantioselectivity. In contrast, the amidase activity was strongly dependent upon substrate structure. In general, the biocatalyst displays a strong preference for the unsubstituted phenyl side chain or /wa-substituted phenyl side chain compared with ortho- or meta-, and this is manifest both with respect to observed conversion and rate and also observed enantioselectivity. In contrast, the biotransformations of... 

One procedure for the synthesis of these title ring systems appeared recently <2003S1079>. Yadav and Kapoor described that the transformation of some oxadiazole and thiadiazole derivatives bearing specially substituted methylsulfinyl side chain 131, when reacted with thionyl chloride, give ring-closed compounds 134. The reaction was carried out in pyridine under reflux conditions in 74-79% yield. As shown in Scheme 25, the authors assume that the first step is the formation of the sulfonium salt 132 which undergoes cyclization with hydrogen chloride and sulfur dioxide elimination to 133 and, finally, demethylation of this intermediate leads to the final product 134. 

Nuclear aromatic substitution occurs by way of an ECiyECfi-sequence as shown in Scheme 9, path (b). It occurs at the carbon atom with the highest positive charge density and in alkylbenzenes competes with side chain substitution via an ECgEC/v process by deprotonation of the radical cation to form a benzyl radical. 

There are numerous patents claiming 3-hydrazinopyridazine derivatives with amino-substituted alkoxy side-chains at C-6 as ff-blocking vasodilating agents [188,286-293]. Other 3-hydrazinopyridazine-derived antihypertensive agents are covered by patents [294-301], or described in the literature [302 306]. It should be noted that with structurally very simple hydrazino-pyridazines like 6-hydrazino-3-pyridazinecarboxamide (hydracarbazine, 2105 TH CAS 3164-47-9), antihypertensive activity has been observed. 

The most common Hj antihistamine drugs are structurally similar to histamine with a substituted ethylamine side chain however, they have two aromatic rings and can be formally represented by the general formula ... 

A fused tricyclic ring system based on an indole provides yet another NSAID. Michael addition of the anion from diethyl methylmalonate to cyclohexanone followed by acid hydrolysis of the product gives cyclohexanone (21-3), which incorporates the characteristic profen 2-substituted carboxylic side chain. Sequential reaction with para-chlorophenylhydrazine and a strong acid gives the fused indole... 

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