Transformation of side chains

Functional groups on a benzene ring can generally be converted into other functional groups without any reaction of the stable aromatic ring. 

Oxidation of a methyl substituent. Strong oxidising agents (such as potassium permanganate, KMn04) can convert a methyl group into a carboxylic acid (e.g. PhCOjH). 

Bromination of an alkyl substituent. A-Bromosuccinimide (NBS) can bromin-ate at the benzylic position (i.e. at the carbon atom attached to the benzene ring) via a radical chain mechanism. It should be noted that the intermediate benzylic radical is stabilised by resonance (i.e the radical can interact with the JT electrons of the benzene ring). 

The CHj carbon atom in toluene is at oxidation level 0 the CO2H carbon atom in benzoic acid is at oxidation level 3 (Section 4.5) 

For a related radical reaction involving a peroxide, see Section 6.2.2.1 

On heating, the aryl diazonium ion can produce nitrogen gas (an excellent leaving group) and a very unstable aryl cation in an SN1 mechanism, which can react with nucleophiles. 

The reactions involving copper salts are known as the Sandmeyer reactions. These reactions proceed via radical, rather than ionic, mechanisms. 

Aryl diazonium salts can also undergo coupling reactions with phenol or aromatic amines, which possess nucleophilic OH or NH2 groups, respectively. This electrophilic substitution reaction (with the diazonium salt as the electrophile) produces highly coloured azo compounds. 

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Data on transformations of side chains are limited to the reactivity of substituents attached to ring carbons. Reactivity of the rings typically includes electrophilic substitution on heteroatoms and oxidative/reductive sequences involving variety of thiocines. 

In spite of the diverse classes of steroid compounds, at the present time they are all connected with one another by partial syntheses which enable us to pass from one class to another by complicating or simplifying the structure through the introduction, elimination, or transformation of side chains and functional substituents. The establishment of synthetic links between all the classes of steroids enables us to classify as total synthesis, properly so-called, only the construction of the cyclopentano-... 

If the individual residues of a peptide are transformed into the corresponding peptoid monomers to make hybrid oligomers, there will be a perturbation in the distance between side chains at the boundary between oligomer types. That is, spacing of side chains at a peptoid-peptide linkage will be different from that between either two peptide or peptoid residues. 

The Michael addition of nitro compounds is a useful method for the preparation of various natural products. The Michael addition of nitroalkanes to dehydroalanines gives y-nitro-a-amino acids, which provides a convenient synthesis of side-chain modified a-amino acids (Eq. 4.114).152 Transformations of y-nitro-a-amino acid derivatives into a-amino acids occur by reductive denitration (see Section 7.2) into y-oxygenated a-amino acids by the Nef reaction (Eq. 

Some more or less routine transformations with side chains of tetrazolo[l,5-tf]pyridine or its benzologue have also been published during the recent period, and these results are shown in Scheme 19. 

Beyond the well-defined substitutions of the heterocyclic ring systems, numerous other transformations have been carried out that cannot be simply classified into the substitution category. These transformations involve side chain alkylations, exchange of substituents by more sophisticated methods, or ring closures carried out on the side chains. A set of such reactions are summarized in Table 3. 

Transformation of a phosphonio-substituted phospholide derivative under conservation of the r-electron system has been demonstrated in a number of cases which include substitution of a ring-hydrogen atom, replacement of a PRs -moiety by a hydride, or reductive de-arylation of a PhsP " - to a phosphinyl substituent PPh2. Subsequent re-quaternisation of the latter allows the formal substitution of a PhsP " - by a modified Ph2(R)P -moiety in a two-step reaction. The application of this scheme is not only perfectly suitable for the synthesis of bis-phosphonio-benzophospholides with different phosphonio-moieties but, since the last reaction stage tolerates a variety of functional groups in the electrophile, offers as well a convenient pathway for the synthesis of side-chain functionalised phosphonio-phospholide derivatives from more simple substituted precursors. 

N-Oxides undergo a number of side-chain transformations in which the ring system remains intact (Scheme 40). " Formation of 157 presumably occurs via the isocyanate, but attempts to trap this with water or ethanol failed. 

Fig. 230. Left—Atoms of the benzene ring lie on the sets of parallel broken lines these lead to strong regions of the transform in the directions of the arrows. Centre—A helix gives strong regions in the transform in directions perpendicular to the broken lines. Right—The effect of side chains is to move strong regions nearer to the axis.

The synthesis of unnatural amino acids and peptides is of great interest since it offers the possibility to design new biologically active protein analogues. One of the possible interesting transformations is side chain oxidation of amino acids, for which MTO can be used. It is reported that various /V-Boc protected amino acids such as methionine (Met), cysteine (Cys), and tryptophan (Trp) can be oxidized with the MT0/H202 system [108]. 

There are many reactions of cyclophosphazene derivatives involving substitution or transformations at side chains that do not affect the... 

We have only dealt with the main chain nematic networks so far. Actually many liquid crystalline networks are formed by crosslinking the backbones of side chain liquid crystalline polymers. The side chain nematic polymers have three nematic phases and their backbones have either prolate or oblate conformations, depending on their phase. It is expected that the rubber elasticity of a side chain nematic polymer network is more complex. For instance, the stress-induced Ni-Nm phase transition is predicted as the network shape transforms from oblate to prolate. Liquid crystalline networks have a bright potential in industry. 

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