Esterification site-selective

Such generalisations can, however, be misleading as the various hexopyr-anoses exhibit slightly different reactivity patterns and the anomeric configuration can be critical in determining the site selectivity. In particular, when a (protected) anomeric hydroxyl is cis to the 2-OH it is often found that the 2-OH shows enhanced reactivity towards etherification and esterification as exemplified by benzylation of methyl 4,6-O-benzylidene a-D-glucopyranoside under basic conditions (Figure 2.3) [6]. 

At an industrial scale, the esterification catalyst must fulfill several conditions that may not seem so important at lab-scale. This must be very active and selective as by-products are likely to render the process uneconomical, water-tolerant and stable at relatively high temperatures. In addition, it should be an inexpensive material that is readily available on an industrial scale. In a previous study we investigated metal oxides with strong Bronsted acid sites and high thermal stability. Based on the literature reviews and our previous experimental screening, we focus here on application of metal oxide catalysts based on Zr, Ti, and Sn. 

Product distributions obtained on esterification of nucleosides and nucleotides under basic conditions throw further light on factors affecting selective reactivity. p-Toluenesulfonylation of adenosine 5 -monophosphate in aqueous alkali yielded exclusively (in 54-61% yield) the 2 -p-toluenesulfonate.107 Lack of reaction at HO-3 was attributed either to formation of a phosphoric p-toluenesulfonic anhydride, which sterically protected this hydroxyl group, or to the higher acidity of HO-2. It has been shown that the acidic site (with pKa 12.5) in adenosine is associated with the presence of both HO-2 and HO-3, as replacement of either of these by hydrogen, or of HO-2 by methoxyl, results in loss of this acidity.108 Inductive effects, or the sta-... 

Scheme 12 Selective esterification of sucrose over silica-supported strongly basic guanidine sites...

Jacobs and coworkers reported the catalytic activity of a mesoporous silica-supported sulfonic sites in the esterification of sorbitol with lauric acid [130]. This reaction affords in a one step process the dilauryl isosorbide (dehydration of sorbitol/esterification). In contrast to zeolites, it is found that mesoporous silica-supported sulfonic sites afford the corresponding dilauryl isosorbide with 95% selectivity at 33% conversion (Scheme 13). 

Comparison of Figs. 3 and 4 reveals that alcohol chain length exerted more influence on ester yield than the acid carbon size. For alcohol size varying from C5 to C8, conversion was lower than 40%, and for acid size from C4 to Cl6, similar esterification yields (60-80%) were found. These results may reflect both the intrinsic selectivity of the enzyme and different accessibility of substrates to enzyme active site (22). 

The difference in initial slope is attributed to the different number of catalytic sites involved in the two reactions. If water is stripped from the liquid, coverage of the catalyst surface with water molecules decreases, and in consequence both reactions are running faster. However, the increase of ether formation is proportional to the square of the progress of the esterification, because of the square in the adsorption term in the ether rate expression (3). Therefore, stripping of water increases the rates, but lowers the selectivity at low conversion levels. 

For the esterification of terephthalic acid with ethylene glycol at 473 K, SO /TiCh calcined at 773 K is much more active than SiC -A Ch as shown in Fig. 6 [60]. The SO /TiCh showed a maximum activity when calcined at 573 K for the esterification of oleic acid with glycerol and of propionic acid with butanol at 403 K [61], where the active sites were attributed to Bronsted acid sites from a correlation between the activity and the Bronsted acidity. The esterification of phthalic anhydride with 2-ethylhexanol to form dioctyl phthalate is also efficiently catalyzed by solid super-acids, the selectivity being more than 90% [62]. The... 

Amorphous Sn-, Si-, and Al-containing mixed oxides with homogeneous elemental distribution, elemental domains, and well-characterized pore architecture, including micropores and mesopores, can be prepared under controlled conditions by use of two different sol-gel processes. Sn-Si mixed oxides with low Sn content are very active and selective mild acid catalysts which are useful for esterification and etherification reactions [121]. These materials have large surface areas, and their catalytic activity and selectivity are excellent. In the esterification reaction of pentaerythritol and stearic acid catalytic activity can be correlated with surface area and decreasing tin content. The trend of decreasing tin content points to the potential importance of isolated Sn centers as active sites. 

Arylboronic acids [63,72,80,85,194] have been most extensively studied as binding sites for derivatised monosaccharides. By using an amino group in the position ortho to the boronic add the rate constant for the esterification with a diol has been increased by a factor of 10 , as mentioned above [79], It has also been shown that the flexibility of the boronic add group is crucial. If the binding interaction is too rigid or too flexible, it is detrimental to the selectivity of the... 

With the addition of a catalytic centre, an imprinted recognition site can be transformed into an enzyme mimetic material offering substrate selective catalysis. Over the past decade a few research groups have studied catalytic effects of imprinted metal oxides in esterification reactions. In this section a brief overview will be given on their efforts to understand the catalytic selectivity and structure of the active site. For additional reading an excellent review can be found by Davis et al. [46]. 

The first use of imprinted metal oxides for catalysis was performed by Morihara et al. in the late 1980s [47,48]. Substrate selective catalytic sites for the esterification of anhydrides were prepared using an alumina sol-gel technique formed on silica gel. Template molecules, present during the final stages of alumina gel formation, are thought to leave footprint-like impressions on the gel surface after subsequent... 

Esterification of acetic acid with C2-C4 alcohols is studied over H(3, HZSM-5, HY, DHY (dealuminated Y) and Y-AI2O3 in the temperature range 100-150 C using different feed rates of 1 1 (mole ratio) acetic acid alcohol mixture. High conversion and selectivity obtained on Hp-zeolite show that Hp zeolite has suitable acidity / acid site strength that is required to carry out esterification reaction. 

Highly conservative modifications such as replacement of aspartate with glutamate or asparagine are possible with site-directed mutagenesis. Notably, however, the first demonstration was from Imoto and co-workers, who used a chemical approach that involved selective esterification followed by ammonolysis to produce Asn-52 (245). The derivative lost 97 to 99 % activity (depending on the pH) and had a twofold to threefold reduction in substrate affinity. The identical derivative, prepared by site-directed mutagenesis where unambiguous and complete substitution is assured, had comparable reductions in catalysis and substrate affinity (14J). 

The first-order rate constant of the esterification of anhydrous phthalic acid catalyzed by nickel sulfates mounted on alumina and some other solid acids is shown in Table IV, together with the acidity of the catalysts measured by using p-dimethylaminoazobenezene as an indicator and the acidity calculated from the rate constants (cf. Section II). The catalytic activity correlates better with the acidity obtained by the latter method. The acidities measured by both methods coincide in the case of nickel sulfate, but do not in the case of silica-alumina. This is considered, according to Tarama et al., to be due to the fact that the Lewis acid sites which are assumed to be included in silica-alumina do not show catalytic activity. However, this might also be interpreted as due to the differences in acid strength and selectivity. 

Coumaric acid 28 presents a more ambitious problem because difTerential protection of two competing anionic sites is to be observed In the absence of 24 any possible esterification and etherification product is formed but adding a slight excess of host 24 switches the reaction paths to the exclusive production of the ester. The absolute reaction rate drops considerably indicating that host-guest complexation effects both reaction centers of the substrate. Nevertheless the differences in their reactivities are stressed by virtue of this dynamic protection preferentially at the phenolate thus enabling the enhancement of reaction selectivity. 

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