Oxyalkylation

Hydrogen abstraction from a position a to the oxygen of alcohols and ethers provides a simple route to a-oxyalkyl radicals. Resonance stabilization and polar factors have been used to explain the ease of radical attack on these substrates. Recent studies appear to exclude the possibility that the oxygen atom in position a to the free C-radical may cause stabilization by resonance. The ease of hydrogen abstraction Avould be determined only by polar factors, arising with electrophilic radicals (X ) in contributions from the polar forms 13-15 to the transition state. 

The a-oxyalkyl radicals used for alkylating heteroaromatic bases are formed by the oxidation of alcohols and ethers with a variety of electrophilic radicals or photochemically. 

Oxidation of alcohols with a variety of oxidizing agents leads to a-hydroxyalkyl radicals. These attack protonated heteroaromatic bases only when obtained from methanol or primary alcohols, with secondary alcohols no attack takes place, probably owing to the ease with which such a-hydroxyalkyl radicals are oxidized. (This limitation does not apply to radiation-induced oxyalkylation, see later.) 

The best results have been obtained by oxidation with peroxydi-sulfate. The formation of hydroxyalkyl radicals was originally interpreted according to the mechanism of Eqs. (40) and (41). 

Buratti, G. P. Gardini, F. Minisci, F. Bertini, R. Galli, and M. Perchi-nuimo. Tetrahedron 21, 3655 (1971). 

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Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

Reaction of olefin oxides (epoxides) to produce poly(oxyalkylene) ether derivatives is the etherification of polyols of greatest commercial importance. Epoxides used include ethylene oxide, propylene oxide, and epichl orohydrin. The products of oxyalkylation have the same number of hydroxyl groups per mole as the starting polyol. Examples include the poly(oxypropylene) ethers of sorbitol (130) and lactitol (131), usually formed in the presence of an alkaline catalyst such as potassium hydroxide. Reaction of epichl orohydrin and isosorbide leads to the bisglycidyl ether (132). A polysubstituted carboxyethyl ether of mannitol has been obtained by the interaction of mannitol with acrylonitrile followed by hydrolysis of the intermediate cyanoethyl ether (133). 

All lene Oxides and Aziridines. Alkyleneamines react readily with epoxides, such as ethylene oxide [75-21-8] (EO) or propylene oxide [75-56-9] (PO), to form mixtures of hydroxyalkyl derivatives. Product distribution is controlled by the amine to epoxide mole ratio. If EDA, which has four reactive amine hydrogens, reacts at an EDA to EO mole ratio which is greater than 1 4, a mixture of mono-, di-, tri,-, and tetrahydroxyethyl derivatives of EDA are formed. A 10 1 EDA EO feed mole ratio gives predominandy 2-hydroxyethylethylenediamine [111-41-1], the remainder is a mixture of bis-(2-hydroxyethyl)ethylenediamines (7). If the reactive NH to epoxide feed mole ratio is less than one and, additionally, a strong basic catalyst is used, then oxyalkyl derivatives, like those shown for EDA and excess PO result (8,9). 

Other polyamine derivatives are used to break the oil/water emulsions produced at times by petroleum wells. Materials such as polyether polyols prepared by reaction of EDA with propylene and ethylene oxides (309) the products derived from various ethyleneamines reacting with isocyanate-capped polyols and quaternized with dimethyl sulfate (310) and mixtures of PEHA with oxyalkylated alkylphenol—formaldehyde resins (311) have been used. 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

M. Hofinger, W. Bose, M. Hille, and R. Bohm. Quaternary oxyalkyl-ated polycondensates, process for their manufacture and their utilization (Quatemare oxalkylierte Polykondensate, Verfahren zu deren Herstellung und deren Verwendung). Patent EP 212265,1987. 

V. N. Koshelev, A. P. Krezub, D. M. Ponomarev, Y. N. Mojsa, N. V. Frolova, A. I. Penkov, and S. V. Vasilchenko. Drilling solution with improved lubricating and rheology—contains additionally oxyalkyl-ated alkylphenol with nitrogen-containing additive, in aromatic solvent. Patent SU 1797617-A, 1993. 

P2 Cross-linked polypropylene glycol 0P1 Oxyalkylated trimethylol propane ... 

These reactions may be considered to be a method of obtaining 1,3,2,5-dioxaborataphosphoniarinanes with different substituents at carbon and phosphorus atoms of the ring. Comparing the properties of cyclic oxyalkyl-phosphines and boryloxyalkylphosphines, it should be noted that in both cases the reaction with alkyl halides results in the formation of a tertiary phosphonium salt. The reaction with electrophilic reagents such as diphe-nylchlorophosphine and diphenylchloroborane proceeded quite differently [Eq. (100)]. 

One more reaction route was shown for the interaction with ethylene oxide [Eq. (102)]. In the present case, one could expect the substitution of the a-oxyalkyl fragment of boryloxyalkylphosphine by /3-oxyalkylphos-phine, as observed for a-oxyalkylphosphines (88IZV155). 

Different reactivity of a-oxyalkyl and boryloxyalkyl fragments was revealed in reactions with amines of weak basicity. For example, in the reaction with diphenylamine or o-aminobenzoic acid with a reagent ratio of 1 1, substitution of the oxymethyl group by the aminomethyl one takes place [Eq. (117)]. The P,B-containing heterocycle is retained (89IZV1340). 

Prodrugs That Incorporate an Oxyalkyl, Hydroxyalkyl, or Arylalkyl Pro-Moiety... 

Hydrogen peroxides, <-butyl hydroperoxide, and ammonium peroxy-disulfate have been used for the oxyalkylation of protonated heteroaromatic bases by the ethers dioxane, tetrahydrofuran, 1,3-dioxolan,... 

Acyclic ethers undergo partial j8-scission with formation of carbonyl and alkyl derivatives. Thus with ethyl ether the introduction of the oxyalkyl group is accompanied by appreciable quantities of ethyl and acetyl derivatives, attributed to jS-scission of the a-oxyalkyl radical [Eq. (47)]. 

For unsaturated compounds with electron-withdrawing substituents (carb-oxyalkyl, nitro, nitrile, vinyl), polymerization can be initiated anionically (e.g., by OH, NH2 , or carbanions). 

Fmoc-Rink-Nle-pMeBHA-resin (1 g, 0.55 mmol g ) was swollen for 1.5 h in NMP in a reaction vessel equipped with a sintered glass bottom, and placed on a shaker. The Fmoc group was removed with 20% piperidine in NMP (8mL, 2 x 15 min) and after washing with NMP (8mL, 5 x 2 min), the Fmoc removal was monitored by the ninhydrin Kaiser test. Coupling of building blocks such as iV -Fmoc-/Va>-carb-oxyalkyl(OAl)Xaa-OH or /V -Fmoc-/V" -aminoalkyl(Aloc)Xaa-OH, or N -alkylated amino acids such as... 

Oxyalkylated compounds in deposit Indicates the presence of water- or oil-soluble cleaning agents or the presence of demulsifying agents... 

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