Acetals alcohol protection

Emulsion Adhesives. The most widely used emulsion-based adhesive is that based upon poly(vinyl acetate)—poly(vinyl alcohol) copolymers formed by free-radical polymerization in an emulsion system. Poly(vinyl alcohol) is typically formed by hydrolysis of the poly(vinyl acetate). The properties of the emulsion are derived from the polymer employed in the polymerization as weU as from the system used to emulsify the polymer in water. The emulsion is stabilized by a combination of a surfactant plus a coUoid protection system. The protective coUoids are similar to those used paint (qv) to stabilize latex. For poly(vinyl acetate), the protective coUoids are isolated from natural gums and ceUulosic resins (carboxymethylceUulose or hydroxyethjdceUulose). The hydroHzed polymer may also be used. The physical properties of the poly(vinyl acetate) polymer can be modified by changing the co-monomer used in the polymerization. Any material which is free-radically active and participates in an emulsion polymerization can be employed. Plasticizers (qv), tackifiers, viscosity modifiers, solvents (added to coalesce the emulsion particles), fillers, humectants, and other materials are often added to the adhesive to meet specifications for the intended appHcation. Because the presence of foam in the bond line could decrease performance of the adhesion joint, agents that control the amount of air entrapped in an adhesive bond must be added. Biocides are also necessary many of the materials that are used to stabilize poly(vinyl acetate) emulsions are natural products. Poly(vinyl acetate) adhesives known as "white glue" or "carpenter s glue" are available under a number of different trade names. AppHcations are found mosdy in the area of adhesion to paper and wood (see Vinyl polymers). 

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by methylthiomethyl chloride is efficient if catalyzed by iodide ion.9 Alcohols are also converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride10 or with benzoyl peroxide and dimethyl sulfide.11 The latter two methods involve the generation of the methylthiomethylium ion by ionization of an acyloxysulfonium ion (Pummerer reaction). 

T. Mukaiyama, M. Ohshima, and M. Murakami, 2-Benzyloxy-propene A novel protective reagent of hydroxyl groups, Chem Lett 265 (1984) T. Mukaiyama, M. Ohshima, H. Nagaoka, and M. Murakami, A novel acid-resistant acetal-type protective group for alcohols, Chem. Lett 615 (1984). 

Alcohols protected as esters, and diols protected as cyclic acetals resist Jones oxidation. 

An intermediate in the synthesis of laulimalide by Davidson8 illustrates the differential protection of alcohols. The starting materials 56 and 57 already have an alcohol protected as a TBDMS silyl ether and a diol protected as an acetal. The alcohol in 58 is protected as a p-methoxybenzyl ether and the acetal hydrolysed by acetal exchange to give the free diol 60. Selective protection of the primary alcohol by a bulky acyl group (pivaloyl, i-BuCO ) 61 allows silylation of the secondary alcohol with a TIPS group 62. Finally the pivaloyl group is selectively removed by DIBAL reduction to release just one free alcohol 63. 

An alternative sequence to avoid dimer formation in the synthesis of bosentan has appeared in the patent literature. The SNAr reaction with ethylene glycol is carried out first and the primary alcohol protected as the acetate ester 30. The second displacement with sulfonamide 24 and saponification of the ester protecting group then provide bosentan (l).29 This route is reported to provide the product in high purity and yield, but lacks the advantages of improved throughput afforded by the optimized route. 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

Hydration with boranes proved difficult due to extensive reductive cleavage of the epoxide (Scheme 45). The best results (54%) were achieved with borane in THF. The subsequent oxidation with basic hydrogen peroxide led to the primary alcohol as well as to saponification of the acetate. Selective protection of the primary alcohol 397 as trichloroethyl carbonate was followed by oxidation with RuCl3/NaI04, thereby producing not only the y-lactone but also the cyclic ketone. 

As shown in Scheme 11.84, glucal derivative 409 was oxidized to the corresponding aldehyde, which was treated with the lithium derivative of phenylacetylene to give a mixture of alcohols protected as their acetates 410. lodoglycosylation of the glycal with 4-methoxybenzyl alcohol gave... 

The stability of ethers and mixed acetals as protecting groups for alcohols varies from the very stable methyl ether to the highly acid-labile trityl ether. However, all ethers are stable to basic reaction conditions. Hence, ether or mixed acetal protecting groups specifically tolerate... 

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