Dioxan transesterification

Cychc carbonates are prepared in satisfactory quaUty for anionic polymerization by catalyzed transesterification of neopentyl glycol with diaryl carbonates, followed by tempering and depolymerization. Neopentyl carbonate (5,5-dimethyl-1,3-dioxan-2-one) (6) prepared in this manner has high purity (99.5%) and can be anionically polymerized to polycarbonates with mol wt of 35,000 (39). 

Early reports on the effects of the choice of solvent on enzymatic enantioselectivity showed that substantial changes may be observed. For the transesterification reaction of sec-phenethyl alcohol with vinyl butyrate catalyzed by subtilisin Carlsberg, a 20-fold increase in the E-value was reported when the medium was changed from acetonitrile to dioxane [59]. Similar changes were recorded for the prochiral selectivity of Pseudomonas sp. lipase in the hydrolysis of 2-substituted... 

When 18-crown-6 was co-lyophilized with a-chymotrypsin, a 470-fold activation was seen over the free enzyme in the transesterification of APEE with 1-propanol in cyclohexane (Scheme 3.2) [96]. There was a low apparent specificity for the size and macrocyclic nature of the crown ether additives, suggesting that, during lyophilization, 18-crown-6 protects the overall native conformation and acts as a lyoprotectant. To examine this global effect, FTIR was used to examine the effect of crown ethers on the secondary structure of enzymes. In one study [98], subtilisin Carlsberg was shown to retain its secondary structure in 1,4-dioxane when lyophi-lized in a 1 1 ratio with 18-crown-6. In addition, examination of FTIR spectra from varying incubation temperatures indicated that an increase in crown ether content in the final enzyme preparation resulted in a decreased denaturation temperature in the solvent, indicating a more flexible protein structure. 

Lipases, which are noted for their tolerance of organic solvents, were obvious candidates for biocatalysis in ionic liquids. Indeed, stable microbial lipases, such as CaLB [8, 54, 55, 56] and Pseudomonas cepacia lipase (PcL) [28, 55, 57] were cat-alytically active in the ionic liquids of the l-alkyl-3-methylimidazolium and 1-alkylpyridinium families, in combination with anions such as [BF4], [PF6], [TfO] and [ Tf2N]. Early results were not always consistent, which may be caused by impurities that result from the preparation of the ionic liquid. Lipase-mediated transesterification reactions (Figure 10.3) in these ionic liquids proceeded with an efficiency comparable to that in tert-butyl alcohol [8], dioxane [57], or toluene... 

Langmuir—Hinshelwood equations, with a surface reaction as the ratedetermining step, were also found suitable for liquid phase transesterifications [435—437]. With ethyl acetate and 1-propanol in dioxan as a sol-... 

Fig. 16. Effect of degree of crosslinking (% DVB) of standard (non-porous) ion exchanger on initial transesterification rate, r° (mol kg-1 h-1), of ethyl acetate with 1-propanol [436]. (1) Liquid phase at 52°C initial composition (mole%), 0.4 ethyl acetate, 0.4 1-propanol, 0.2 dioxan (solvent). (2) Vapour phase at 120°C partial pressure of reactants, 0.5 bar (ester—alcohol ratio 1 1).

These considerations can be formulated by schemes (e)—(g) below (R1 = H or alkyl). Scheme (e), in which the acid (ester) is protonated and alcohol reacts in non-adsorbed state, corresponds to the mechanisms Aac1 or Aac2 proposed for homogeneous esterification and hydrolysis with ion exchanger catalysts, the mechanism (e) was assumed to be operating in the liquid phase esterification of salicyclic acid with methanol [449] and in the transesterification of ethyl acetate with the same alcohol in dioxan as... 

Methylenedioxy)benzyl esters (piperonyl esters) are cleaved more readily than the 4-methoxybenzyl ester by acid hydrolysis with 2 M HBr/AcOH or TFA at room temperature within 5 minutes.3,4-(Methylenedioxy)benzyl esters are readily prepared either by transesterification of anoino acid 4-nitrophenyl esters with 3,4-(methylenedioxy)benzyl alcohol in imidazole/dioxane (rt, 12 h) or from Nps-protected amino acids with 3,4-(methyl-enedioxy)benzyl chloride/TEA in DMF at room temperature. 

In searching for further expansions of dihydropyrimidine scaffold, Kappe and co-workers [359] immobilized 4-chloroacetoacetate on hydroxymethylpolystyrene resin by a microwave-assisted transesterification in 1,2-dichlorobenzene. The subsequent Biginelli condensation with the aldehyde and the urea components was performed in dioxane at 70 °C in the presence of catalytic amounts of HCl. Low yields, observed in the case of two out of twelve aldehyde building blocks employed, were attributed to the low solubility and reactivity of the bisureide side products. Further manipulations of the BigineUi products, involving thermal, amine-, or hydrazine-mediated cyclizations, gave access to various dihydropyrimidine-condensed heterocycles (461), (462), and (464) respectively (Scheme 95). 

Acetylation of horseradish peroxidase increased its half-life at 65°C fivefold and made it more tolerant to dimethyl-formamide, tetrahydrofuran, and methanol.91 Chymotrypsin is more active in organic media when immobilized than when it is just suspended.92 The selectivity of enzymes in organic media can vary with the solvent.93 The transesterification of racemic 1-phenylethanol with vinyl butyrate using subtilisin gave the best enantioselectivity in dioxane (61%) and the least in N-metby 1 acetamide (3%). Pretreatment of a lipase from Candida rugosa in isopropyl alcohol increased the activity slightly and the enantioselectivity by more than tenfold in the resolution of ester 9.5.94 The R isomer had 93.1% enantiomeric excess (ee) the S isomer 94.4%. 

Chemical modification of polymer-bound active ester groups is also subject to strong solvent effects. In copolyfAOTcp-styrere), both aminolysis and transesterification with primary alcohols are positively influenced by solvents in the order of dimethylformamide (DMF) > dioxan > diloroform > chlorobenzene > dimethylsulfoxide (DMSO). However, trans-esterification with phenols proceeds in dioxan, but not in DMF. The last-nan d solvent effect is probably related to inactivation of the phenolate ion in DMF, as observed ako for the acylation of polymer-bound phenolic groups by soluble trichlorophenyl esters [64]. 

Transesterification of boronic acid esters s. 44, 52 2-Amino-1,3-dioxanes from 1,3-diols s. 44, 941... 

Since phenacylesters show an enhanced electrophilicity, this type of anchoring function on a polystyrene gel phase is very rapidly and quantitatively cleaved by hydrazinolysis within 2 hours at 8-12 °C. On 0.5% cross-linked supports we are applying a 10% (v) solution of hydrazine hydrate in dioxane/methanol 9 1 (v v). The detachment filtrates are immediately neutralized with solid carbon dioxide as described in the transesterification procedure. 

Hydrolases, especialy lipases, are noted for their tolerance of organic solvents, and are obvious candidates for the enzymatic synthesis in ILs (Sureshkumar Lee, 2009). Indeed, lipases from Candida antarctica, Burkholderia cepacia (formerly Pseudomonas cepacia), and Alcaligenes sp. are catalytically active in ILs (Itoh et al, 2001 Nara et al., 2002). Additionally, lipases mediate transesterification reactions in these ILs with an efficiency comparable to that in tert-butyl alcohol, dioxane, or toluene (Lau et al., 2000 Nara et al., 2002 Park Kazlauskas, 2001). 

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