Acetals reactivity hydroxyl groups

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Since a number of the studies we shall review were concerned with the effect of synthetic chain molecules or micelles on the hydrolysis rate of nitrophenyl acetate and similar esters, it will be useful to consider briefly some characteristics of the enzymic catalysis of this process. A particularly detailed study has been carried out on the enzyme chymo-trypsin (14) and a great deal of evidence shows that the catalytic site of this enzyme contains a serine residue with an unusually reactive hydroxyl group. Denoting the chymotrypsin by Ch—OH, the interaction with the ester involves first acyl transfer to the enzyme and this is followed by acyl enzyme hydrolysis to regenerate Ch—OH ... 

Acetylation methods have been used for many years to improve some properties of wood cellulose such as moisture repellency, dimensional stability and resistance to environmental degradation. Their use for improving the properties of natural fibers has increased significantly in the last decade or so. The methods are based on the reaction of lignocellulosic material with acetic anhydride at elevated temperature, with or without a catalyst. The acetic anhydride reacts with the more reactive hydroxyl groups according to the equation [36],... 

Acetic anhydride is preferable for acetylation with cellulose because it has more reactive hydroxyl groups than acetic acid. Experimentally, natural fibers of interest are normally first soaked in acetic acid and subsequently treated with acetic anhydride. This is to promote the reaction as acetic anhydride does not swell enough cellulose for the reaction. In order to provide a combination effect of the treatment, alkali treatment may be carried out before treating natural fibers with glacial acetic acid followed by acetic anhydride [75-77]. 

Liquid crystal polyesters are made by a different route. Because they are phenoHc esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenoHc hydroxyl groups are acylated with a lower aHphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxyHc acid, sometimes in the presence of a catalyst. The phenoHc polyester forms readily as the volatile lower acid distills from the reaction mixture. Many Hquid crystal polymers are derived formally from hydroxyacids (97,98) and thein acetates readily undergo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Me3SiNEt2- Trimethylsilyldiethylamine selectively silylates equatorial hydroxyl groups in quantitative yield (4-10 h, 25°). The report indicated no reaction at axial hydroxyl groups. In the prostaglandin series the order of reactivity of trimethylsilyldiethylamine is Cii > Ci5 C9 (no reaction). These trimethylsilyl ethers are readily hydrolyzed in aqueous methanol containing a trace of acetic acid. The reagent is also useful for the silylation of amino-acids. ... 

The crotonate esters, prepared to protect a primary hydroxyl group in nucleosides, are cleaved by hydrazi ne (MeOH, Pyr, 2 h). The methoxycrotonate is 100-fold more reactive to hydrazinolysis and 2-fold less reactive to alkaline hydrolysis than the corresponding acetate. ... 

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

The use of dimethyl sulfoxide-acetic anhydride as a reagent for the oxidation of unhindered steroidal alcohols does not appear to be as promising due to extensive formation of by-products. However, the reagent is sufficiently reactive to oxidize the hindered 11 j -hydroxyl group to the 11-ketone in moderate yield. The use of sulfur trioxide-pyridine complex in dimethyl sulfoxide has also been reported. The results parallel those using DCC-DMSO but reaction times are much shorter and the work-up is more facile since the separation of dicyclohexylurea is not necessary. Allylic alcohols can be oxidized by this procedure without significant side reactions. 

Because the ketene acetal-terminated prepolymer is a viscous Liquid at room temperature, therapeutic agents and the triol can be mixed into the prepolymer at room temperature and the mixture crosslink id at temperatures as low as 40°C. This allows incorporation of heat-sensitive therapeutic agents into a solid polymer under very mild conditions of thermal stress. However, because the prepolymer con-tedns reactive ketene acetal groups, any hydroxyl groups present in the therapeutic agent will result in the covalent attachment of the therapeutic agent to the matrix via ortho ester bonds (16). 

Co-adsorption experiments show a complex role of the nature and concentration of chemisorbed ammonia species. Ammonia is not only one of the reactants for the synthesis of acrylonitrile, but also reaction with Br()>nsted sites inhibits their reactivity. In particular, IR experiments show that two pathways of reaction are possible from chemisorbed propylene (i) to acetone via isopropoxylate intermediate or (ii) to acrolein via allyl alcoholate intermediate. The first reaction occurs preferentially at lower temperatures and in the presence of hydroxyl groups. When their reactivity is blocked by the faster reaction with ammonia, the second pathway of reaction becomes preferential. The first pathway of reaction is responsible for a degradative pathway, because acetone further transform to an acetate species with carbon chain breakage. Ammonia as NH4 reacts faster with acrylate species (formed by transformation of the acrolein intermediate) to give an acrylamide intermediate. At higher temperatures the amide may be transformed to acrylonitrile, but when Brreform ammonia and free, weakly bonded, acrylic acid. The latter easily decarboxylate forming carbon oxides. 

Another potential site of reactivity for anhydrides in protein molecules is modification of any attached carbohydrate chains. In addition to amino group modification in the polypeptide chain, glycoproteins may be modified at their polysaccharide hydroxyl groups to form ester derivatives. Esterification of carbohydrates by acetic anhydride, especially cellulose, is a major industrial application for this compound. In aqueous solutions, however, esterification may be a minor product, since the oxygen of water is about as strong a nucleophile as the hydroxyls of sugar residues. 

Deuterated and tritiated tin hydrides have been used to prepare deuterated saccharides93 and tritiated steroids46 from alkyl bromides, (equations 68 and 69). It is important to note that isomerization has occurred at the chiral reaction centre in the saccharide reaction (equation 68). For the steroid, the tin hydride reaction is regiospecific, i.e. it only reacts at the more reactive bromide rather than the less reactive chloride site and does not react with the keto group, the hydroxyl group or the acetal group. 

A report on the acetylation of 2,7-anhydro-/3-D-aZtro-heptu-lopyranose (sedoheptulosan) with acetic anhydride further illustrates the low reactivity of an equatorial hydroxyl group on abridged, pyranoid ring under controlled conditions, 21% of the 1,3,5-tri-O-acetyl derivative may be isolated.60... 

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