Direct Ring Functionalization

Thiophene [110-02-1] and a number of its derivatives are significant in fine chemical industries as intermediates to many products for pharmaceutical, agrochemical, dyestuffs, and electronic appHcations. This article concentrates on the industrial, commercial, and economic aspects of the production and apphcations of thiophene and thiophene derivatives and details the main synthetic schemes to the parent ring system and simple alkyl and aryl derivatives. Functionalization of the ring and the synthesis of some functional derivatives that result, not from the parent ring system, but by direct ring cyclization reactions are also considered. Many good reviews on the chemistry of thiophene and thiophene derivatives are available (1 7). 

The site of attack can also be directed by functionality on the substrate itself, as in the phenyl-boronate-mediated C-2 selective azide ring-opening reaction of trans-2,3-epoxy alcohols (82) by sodium azide. In this reaction, the nucleophile is delivered intramolecularly fiom the azidoboronate intermediate 83. Yields are generally good to excellent <99TL4589>. 

The synthesis and herbicidal activities of various imidazolinthiones, in particular the thiono isosteres of imazapyr, imazethapyr and imazamethabenz are discussed. In the synthesis area it is shown that the imidazolinthione ring functions as an ortho-directing group in aromatic lithiations. In the biological activity area it is shown that replacement of the imidazolinone carbonyl with a thio-carbonyl results in changes in weed toxicity and crop selectivity. 

Schematic illustration of the two strategies used in the preparation of ferrocene-functionalized polymer brushes (a) hydroxyl groups of the PHEMA brushes activated by CDl, followed by coupling with FCNH2 and (b) epoxy groups of the PGMA brushes underwent direct ring-opening reaction with FcNHj. (Reprinted with permission from Wu et al. 2009. Electrochemical Biosensing Using Amplification-by-Polymerization. Analytical Chemistry 81 (16) 7015-7021, copyright (2(X)9) American Chemical Society.)...

C-alkylation, directed condensation, -cycloaddition, direction of -functionalization, — halogenation, directed nitration, direction of -ring opening, —... 

The direct a-functionalization of natural peptides takes advantage of existing structure and provides rapid access to diverse new peptides. In 2008, Li reported a new method for functionalizing peptido-amides through the CDC reaction at ot-peptido C-H bonds (Scheme 3.13). To realize this process, 2.0 equiv. of Cu(OAc)2 and 20 mol% of ligand are necessary, due to the formation of an active six-membered ring complex. In addition, the presence of a catalytic amount of base is beneficial to the reaction. 

Many aromatic aldehydes (having the -CHO group joined directly to the benzene ring) undergo polymerisation when heated with a solution of potassium cyanide in aqueous ethanol. Thus benzaldehyde gives benzoin, a compound of double function, since it contains both a secondary alcoholic and a ketonic... 

Takamizawa et al. developed a general ring-expansion reaction of heterocycles that, applied to thiazolium salts, yields 1,4-thiazines (496, 497) thiamine (220) reacts with dialkyl acylphosphonates (221) to give the tricyclic 1,4-thiazine (222) (498), which is easily hydrolyzed to dihydro-1,4-thiazinone (223) (499) (Scheme 106). In the case of thiazolium slats containing no functional groups (224), 1,4-thiazine derivatives (226) were directly obtained in fairly good yields (Scheme 107). 

In this chapter we examine in turn the properties of alkyl and aryl-thiazoles that do not possess functional groups bonded directly to the thiazole ring. The general trends are underlined, and the applications of certains thiazole compounds in such areas as polymers, flavorings, and pharmacological and agricultural chemicals are discussed. 

These preceding properties imply that the thiazole has to be introduced in various molecules, by direct cyclization or with precursors already bearing the thiazole ring. Among these last products the clomethiazole. nitrothiazole, and aryl or alkylthiazoles with the functional group on the aryl or alkyl substituent have been widely used. 

Appreciable interaction between chromophores does not occur unless they are linked directly to each other, or forced into close proximity as a result of molecular stereochemical configuration. Interposition of a single methylene group, or meta orientation about an aromatic ring, is sufficient to insulate chromophores almost completely from each other. Certain combinations of functional groups afford chromophoric systems which give rise to characteristic absorption bands. 

The direction of nucleophilic ring opening of unsymmetrical perfluoroepoxides has been shown to be a function of the nature of the nucleophile and the solvent (23,28). Although many oligomeric products have been prepared by this procedure and variations of it, no truly high polymers have been obtained... 

Cycloaliphatic amines are comprised of a cyclic hydrocarbon stmctural component and an amine functional group external to that ring. Included in an extended cycloaUphatic amine definition ate aminomethyl cycloaUphatics. Although some cycloaUphatic amine and diamine products have direct end use apphcations, their major function is as low cost organic intermediates sold as moderate volume specification products. 

The N-oxide function has proved useful for the activation of the pyridine ring, directed toward both nucleophilic and electrophilic attack (see Amine oxides). However, pyridine N-oxides have not been used widely ia iadustrial practice, because reactions involving them almost iavariably produce at least some isomeric by-products, a dding to the cost of purification of the desired isomer. Frequently, attack takes place first at the O-substituent, with subsequent rearrangement iato the ring. For example, 3-picoline N-oxide [1003-73-2] (40) reacts with acetic anhydride to give a mixture of pyridone products ia equal amounts, 5-methyl-2-pyridone [1003-68-5] and 3-methyl-2-pyridone [1003-56-1] (11). 

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