Thioethers from amides

SECTION 126 Ethers, Epoxides, and Thioethers from Amides... 

SECTION 126 ETHERS, EPOXIDES AND THIOETHERS FROM AMIDES... 

In heterodetic peptides, the ring system is formed from amides and other heteroatom linkages, for example, a disulfide bridge, a thioether or a lactone linkage. The most common nonamide links in heterodetic peptides are the disulfide bonds (found in posterior pituitary hormones such as oxytocin and vasopressin) and the ester (lactone) fnnction. " ... 

Metabolites derived by loss of an alkyl or arylalkyl group from ethers [Eq. (4)], thioethers [Eq. (5)], amines [Eq. (6)], and amides [Eq. (7)] represent common biotransformation pathways (R, R" = H, alkyl or aryl). These processes involve oxidation on carbon adjacent to the heteroatom. The intermediates are generally unstable and readily decompose to the corresponding alcohol, thiol, amine, or amide and an aldehyde. Intermediates formed from amides [Eq. (7)] are more stable and may be detected as excreted metabolites. If a secondary carbon atom is adjacent to the heteroatom, then this portion of the molecule is released as a ketone. The heteroatom may also be located in a cyclic structure (e.g., morpholine, piperazine). Two processes have been adopted for amines, namely, N-dealkylation or deamination, that are essentially the same event. In general, which of the two terms applies depends on the... 

Captodative alkenes 67 can be dialkylated, for example, by addition of iso-butyronitrile radical derived from thermal decomposition of AIBN under the same conditions as those which lead to polymerization of other acrylic alkenes. For example, a-morpholino-acrylonitrile (67, c = CN, d = N(CH2CH2)20) leads to 69, in 71% yield (Scheme 12) [4a]. With a-/-butylthio-acrylonitrile (67, c = CN, d = SC(CHj)3), the same process leads to 70 in 88% yield [7]. The adduct radical 68 is highly stabilized, and is in equilibrium with dimer 70. The reaction is quite general, and has been applied to other captodative alkenes (c = CN, COR, CO2R and d = NR2, OR, SR) together with various sorts of radical partners, derived from alkanes, alcohols, thiols, thioethers, amines, amides, ketones, aldehydes, acetals and thioacetals [44, 45]. 

This article describes the successful synthesis of ordered poly(acylhydrazide-amide-thioether) from two nonsymmetric monomers, 4-nitrophenyl acrylate (XabX) and 4-aminobenzhydrazide (ZefZ) with a pmr of synunetric monomers (YcdY), 4,4-thiobisbenzenethiol (YccY) and isophthdic acid (YddY) in the presence of the condensing agent diphenyl(2,3-dihydro-2-thioxo-3-l nzoxazolyl)-phosphonate (1). 

Primary phosphines (R-PHj) are an important ciass of compounds in organophosphorus chemistry. Aithough discovered over a century ago, their chemistry and appiications have gained prominence in recent years. This review discusses recent deveiopments on synthesis, moiecuiar structure, properties, and appiications of primary phosphines. In particular, discussions on synthesis and properties emphasize recent results from our laboratory on the chemical architecture of amide, thioether, and carboxylate functionalized primary bisphos-phines. The utility of bromo- and aminopropyl phosphines (X(CH2)3PH2 X=Br or NH2) as building blocks to produce designer primary phosphines that display exceptional oxidative stability is described. The review also discusses the utility of carboxylate functionalized primary phosphines for incorporation on to peptides and their potential applications in catalysis and biomedicine. 

Nucleophilic aromatic displacement is invoked for incorporation of the side chain in yet another benzimidazole. Thus, treatment of 2,5-dinitroacetanrlide (52-1) with the anion from mercaptomethylcyclohexane leads to the unusual displacement of one of the nitro groups and the formation of thioether (52-3). This intermediate is then converted to diamine (52-4) by sequential reduction and hydrolysis of the amide. Condensation with the same thiourea derivative as above affords dribenda-zole (52-5) [55]. 

The reduced basicity of phenothiazine nitrogen requires that even acylation proceed via the anion. The amide (34-2) from the methyl thioether (34-1) can be prepared, for example, by sequential reaction with sodium amide and acetic anhydride. Oxidation of that intermediate with peracid proceeds preferentially on the more electron-rich alkyl thioether to give the sulfone this affords the phenothiazine (34-3) on hydrolysis of the amide. Complex side chains are most conveniently incorporated in a stepwise fashion. The first step in the present sequence involves reaction of (34-3) as its anion with l-bromo-3-chloropropane to give (34-4). The use of that halide with alkylate piperidine-4-carboxamide (34-5) affords the antipsychotic agent metopimazine (34-6) [35]. 

Figure 384 A PEG—amine compound, such as the Jeffamine polymers from Texaco, may be reacted with this heterobifunctional cross-linker to form amide bond derivatives terminating in maleimide groups. This results in a homobifunctional reagent capable of cross-linking thiol molecules. Subsequent reaction with sulfhydryl-containing molecules yields thioether linkages.

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