Side-chain metallation

Paint Driers and Polymer Additives. Paints based on alkyd resins (qv) dry by the oxidation and cross-linking of unsaturated side chains. Metal catalysts are included in paint formulations to promote this drying. Cerium carboxylates, eg, the naphthenate, are used as through driers, ie, to promote drying in the body of the paint film rather than at the film s surface (44). 

Figure 3.1 Principal protein amino acid side-chain metal-ion binding modes (the metal ion represented as a dark filled circle) and (right) the structure of the Ca2+-binding y-carboxyglutamate found in proteins of the blood-clotting cascade.

However, the results obtained are highly dependent on the nature of the substituents, and when the 5-substituent is a methyl, alkoxymethyl, or alkylthiomethyl group, side-chain metalation becomes the predominant reaction type (Scheme 72) [68JCS(C)172 70CJC2006 76JCS(P1 )994 ... 

However, unlike the situation seen with 2-methyloxazole and 1,2-di-methylimidazole where side-chain metalation predominates, lithiation at C-5 can still be the predominant mode of reaction in certain cases, due to the stronger activating effect of the sulfur atom. The nature of the substituent at C-4, the type of electrophile employed, the temperature of the reaction, and the type of base used can all affect the product ratio (74JOC1192). 

Clarke, A. J. McNamara, S. Meth-Cohn, O. Novel aspects of the metalation of heterocycles. Side-chain metalation of thiophene and ring metalation of six-membered nitrogen heterocycles. Tetrahedron Lett. 1974, 2373-2376. 

When 6-methylphenanthridine is allowed to react with phenyl-lithium in ether, side-chain metalation takes place exclusively.340 The lithiomethyl derivative so obtained forms l,2-bis(6-phenanthri-dyl)ethane in good yield on treatment with oxygen.341... 

The reactions of the isomeric dimethylpyrazines and trimethyl-pyrazine with methyllithium have been studied in order to gain insight into the factors involved in the competition between ring methylation and side-chain metalation.189 The major product from the reaction of 2,5-dimethylpyrazine and ethereal methyllithium was shown to be trimethylpyrazine, thus confirming Klein and Spoerri s earlier observation.190,191 Tetramethylpyrazine was also formed as a by-product. Proof of side-chain metalation was obtained by treatment of the reaction mixture with methyl benzoate and isolation of 2-methyl-5-phenacylpyrazine. Evidence for the presence of dihydro-and tetrahydropyrazine intermediates is derived from the infrared spectrum of the crude product obtained on hydrolysis of the reaction mixture which shows C=N and N-H absorptions (see Scheme 17). 

The major product from the reaction of 2,6-dimethylpyrazine and an ethereal solution of methyllithium is trimethylpyrazine, but 2,3-dimethylpyrazine undergoes exclusive side-chain metalation under... 

Nuclear C-alkylation of alkyl pyrazines has been extensively studied methyl-pyrazines react with organolithium reagents to form products resulting from ring alkylation (or arylation) and side chain metalation (635). 

Boumekouez, A., About-Jaudet, E., and Colhgnon, N., Side-chain metallation of diethyl phosphono-toluenes, J. Organomet. Chem., 466, 89, 1994. 

Side-Chain Metallation of Five-Membered Heterocycles... 

The Diazines Pyridazine, Pyrimidine, and Pyrazine Reactions and Synthesis 269 NH-Protection is also unnecessary for the side-chain metallation of 6-methylpyrimidin-2-one. ... 

Whereas thioanisole, CH3SPh, is reported to give a mixture of ring-metallated and side-chain-metallated products upon interaction with butyllithium, the 0,S-acetal CH3OCH2SPh is lithiated only on the methylene carbon atom by BuLi in THF or sec-BuLi-TMEDA in THF [1-3]. Analogous metallations have been realized with 1,3-oxathiane [4]. The obtained lithium compounds have a limited thermal stability [5], so functionalizations with alkyl halides and epoxides, which are usually less fast than reactions with other electrophiles , give reduced yields. The 0,S-acetal PhSCH2OCH3 can be lithiated in a reasonable time with butyllithium in a THF-hexane mixture but the temperature has to be kept below — 40 °C to prevent decomposition of the lithiated intermediate into PhSLi and other (unidentified) products [5],... 

Block co-polymers exhibit outstanding potential for a variety of applications as a result of their self-assembly into supramolecular structures (see Section 1.2.4). However, the exploration of organometallic multi-block materials was only begun in the early 1990s. Block co-polymers derived from the living anionic polymerization of vinylferrocene have been already briefly mentioned in Section 12.06.2.2.l.(i). In this section, side-chain metal-containing block co-polymers are surveyed. Examples of block co-polymers with metals in the main chain are discussed in Section 3.X. 

For many applications, side-chain metal-containing polymers are sufficient. However, to access the most profound alterations in polymer properties that arise from the presence of metal atoms in a polymer structure, incorporation in the main chain is required. Potential advantages of including metals in the backbone of a polymer rather than the side-group structure include the following ... 

Side-chain metallation of 6-membered heterocycles ( lateral metallation ) ... 

Side-chain metallation of five-membered heterocycles... 

The enaminate anions produced by deprotonating a- and 7-alkylpyridines can participate in a wide range of reactions, " being closely analogous to enolate anions. Similar side-chain carbanion formation is seen in ortho- but not me/a-nitrotoluene. Side-chain metallation of 2-/-butylcarbonylamino-4-methylpyridine proceeds at room temperature. ... 

Protons on alkyl groups at the 1,3-azole 2-positions are sufficiently acidic for strong base deprotonation,and are more acidic than methyl groups at other positions even the assistance of an or/Ao-related carboxylate is usually insufficient to overcome the intrinsic tendency for 2-methyl-lithiation, though an adjacent tertiary amide can do this. The side-chain metallated derivatives can be utilised in reactions with electrophiles. The presence of a 5-nitro group allows much milder, base-catalysed condensations to occur. The condensation at the 2-methyl of thiazoles proceeds in organic acid solution. ... 

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