Butyric acids, esterification with

The D-enantiomer of 393 was obtained in an identical sequence of reactions starting frc m 2,3-0-isopropylidene-4-deoxy-D-threitol (395). This compound was prepared from L-threonine (394) in the following way the amino acid was deaminated to 25 3/ -dihydroxy-butyric acid. Esterification of the carboxyl group and protection of both hydroxyl groups with an isopropylidene grouping gave methyl 4-deoxy-2,3-0-isopropylidene-D-threonate. Reduction of the ester group afforded 395 smoothly. 

Fischer esterification of hydroxyl groups with simultaneous hydrolysis of amorphous cellulose chains using organic acids, such as acetic and butyric acid, mixed with hydrochloric acid to extract CNs has become a viable one-pot reaction methodology that allows isolation of functionalized CNs in a single-step process [25, 26]. Figure 11.4 schematically illustrates the reaction during the process of extraction and... 

One of the most sensitive tests of the dependence of chemical reactivity on the size of the reacting molecules is the comparison of the rates of reaction for compounds which are members of a homologous series with different chain lengths. Studies by Flory and others on the rates of esterification and saponification of esters were the first investigations conducted to clarify the dependence of reactivity on molecular size. The rate constants for these reactions are observed to converge quite rapidly to a constant value which is independent of molecular size, after an initial dependence on molecular size for small molecules. The effect is reminiscent of the discussion on the uniqueness of end groups in connection with Example 1.1. In the esterification of carboxylic acids, for example, the rate constants are different for acetic, propionic, and butyric acids, but constant for carboxyUc acids with 4-18 carbon atoms. This observation on nonpolymeric compounds has been generalized to apply to polymerization reactions as well. The latter are subject to several complications which are not involved in the study of simple model compounds, but when these complications are properly considered, the independence of reactivity on molecular size has been repeatedly verified. 

Chemical Properties. Neopentyl glycol can undergo typical glycol reactions such as esterification (qv), etherification, condensation, and oxidation. When basic kinetic studies of the esterification rate were carried out for neopentyl glycol, the absolute esterification rate of neopentyl glycol with / -butyric acid was approximately 20 times that of ethylene glycol with / -butyric acid (7). 

Cellulose activated with ethylenediarnine [107-15-3] is used to prepare high molecular-weight cellulose butyrate (23). Cellulose so activated has a larger measured surface area (120 m /g) than cellulose activated with acetic acid (4.8 m /g). The diamine is removed with water, followed by solvent exchange with acetic acid and butyric acid before esterification. 

Resolution of racemic alcohols by acylation (Table 6) is as popular as that by hydrolysis. Because of the simplicity of reactions ia nonaqueous media, acylation routes are often preferred. As ia hydrolytic reactions, selectivity of esterification may depend on the stmcture of the acylatiag agent. Whereas Candida glindracea Upase-catalyzed acylation of racemic-cx-methylhenzyl alcohol [98-85-1] (59) with butyric acid has an enantiomeric value E of 20, acylation with dodecanoic acid increases the E value to 46 (16). Not only acids but also anhydrides are used as acylatiag agents. Pseudomonasfl. Upase (PFL), for example, catalyzed acylation of a-phenethanol [98-85-1] (59) with acetic anhydride ia 42% yield and 92% selectivity (74). 

In a typical process for manufacture on a commercial scale bleached wood pulp or cotton linters are pretreated for 12 hours with 40-50% sulphuric acid and then, after drying, with acetic acid. Esterification of the treated cellulose is then carried out using a mixture of butyric acid and acetic anhydride, with a trace of sulphuric acid as catalyst. Commercial products vary extensively in the acetate/ butyrate ratios employed. 

In this context, the esterification of 4-(l-pyrenyl)butyric acid with an alcohol to the corresponding ester was investigated [171]. Without the presence of sulfuric acid no reaction to the ester was foimd in the micro reactor. On activating the surface by a sulfuric acid/hydrogen peroxide mixture, however, a yield of 9% was achieved after 40 min at 50 °C. On making the surface hydrophobic by exposure to octadecyltrichlorosilane, no product formation was observed. Using silica gel in a laboratory-scale batch experiment resulted in conversion, but substantially lower than in the case of the micro reactor. The yield was no higher than 15% (40 min ... 

Chau and Terry [146] reported the formation of penta-fluorobenzyl derivatives of ten herbicidal acids including 4-chloro-2-methyl-phenoxy acetic acid [145]. They found that 5h was an optimum reaction time at room temperature with pentafluorobenzyl bromide in the presence of potassium carbonate solution. Agemian and Chau [147] studied the residue analysis of 4-chloro-2-methyl phenoxy acetic acid and 4-chloro-2-methyl phenoxy butyric acid from water samples by making the pentafluorobenzyl derivatives. Bromination [148], nitrification [149] and esterification with halogenated alcohol [145] have also been used to study the residue analysis of 4-chloro-2-methyl phenoxy acetic acid and 4-chloro-2-methyl phenoxybutyric acid. Recently pentafluorobenzyl derivatives of phenols and carboxylic acids were prepared for detection by electron capture at very low levels [150, 151]. Pentafluorobenzyl bromide has also been used for the analytical determination of organophosphorus pesticides [152],... 

In search of a convenient procedure for preparing diazo substrates for the cycloaddition to Cgg, Wudl introduced the base-induced decomposition of tosyl-hydrazones [116]. This procedure allows the in situ generation of the diazo compoimd without the requirement of its purification prior to addition to Cgg. Since they are rapidly trapped by the fullerene, even unstable diazo compounds can be successfully used in the 1,3-dipolar cycloaddition. In a one-pot reaction the tosyUiydrazone is converted into its anion with bases such as sodium methoxide or butylHfhium, which after decomposition readily adds to Cgg (at about 70 °C). This method was first proven to be successful with substrate 142. Some more reactions that indicate the versatility of this procedure are shown in Table 4.4. Reaction of 142 with CgQ under the previously described conditions and subsequent deprotection of the tert-butyl ester leads to [6,6]-phenyl-C5j-butyric acid (PCBA) that can easily be functionalized by esterification or amide-formation [116]. PCBA was used to obtain the already described binaphthyl-dimer (obtained from 149 by twofold addition) in a DCC-coupling reaction [122]. 

Martins et al. (1991) Batch Esterification of glycidol with butyric acid Porcine pancreatic lipase... 

Mixed ethers result when alcohols and phenols are used with thoria at 390°—420° and esterification takes place when alcohol and acid interact at 350°-400°. Esterification10 is more complete in the presence of titanic oxide at 280°—300°. One molecule of acid is used with twelve molecules of alcohol, and in this way methyl, ethyl, propyl, butyl, and benzyl esters have been prepared from acetic, propionic and butyric acids. 

In addition to the chain length, the effect of branching of the carbon chain was studied. Specificity of POS-PVA lipase was studied by monitoring esterification reactions of ft-butanol, sec-butanol, and ferf-butanol with butyric acid, as shown in Table 2. The highest rate of conversion to ester (60%) occurred in the presence of ft-butanol, compared with sec-butanol and ferf-butanol. The branching was found to decrease significantly the esterification yield by a factor of 0.4 for sec-butanol and 0.65 for tert-butanol. Antczak et al. (24) reported a similar conversion pattern. 

Cellulose esters (e.g., cellulose triacetate, cellulose diacetate, cellulose propionate, and cellulose butyrate) are prepared by initially treating cellulose with glacial acetic acid (or propionic acid and butyric acid) followed by the corresponding acid anhydride with a trace of strong acid as a catalyst in chlorinated hydrocarbon. Complete esterification reactions result in the formation of a triester, which undergoes water hydrolysis to form a diester. Cellulose acetate alone or in combination with cellulose triacetate or cellulose butyrate is used as a semipermeable membrane for osmotic pumping tablets, primarily in controlled release systems. The permeability of the membrane can be further modulated by adding water-soluble excipients to the cellulose esters. 

A very different situation was observed when the resolution of racemic 1,2-0-isopropyhdeneglycerol (IPG or solketal) was studied [19]. In this case, the kinetics of the esterification with butyric acid catalyzed by A. oryzae MIM and R. oryzae CBS 112.07 were investigated by carrying out independent batch tests on the commercially available R- and S-IPG (Table 6.4). 

Table 6.4 Kinetic parameters of R- and S-IPG esterification with butyric acid catalyzed by R. oryzae CBS 112.07 and A. oryzae MIM.

Asper llus oryzae MIM was more enantioselective than R. oryzae CBS 112.07 therefore, it was used for studying the time course of the esterification with butyric acid of (R,S)-IPG under ophmal condihons (Figure 6.2). 

Figure 6.2 Profile of the e.e. of the esterification of (R,S)-IPG with butyric acid under optimized conditions T = 30°C, the concentration of the mycelia = 30g/l, the concentration of (R, S)-iPG = 3g/l, an equimolar concentration of butyric acid, solvent n-heptane, = 0.75, and biocatalyst lyophilized cells of A. oryzae MIM.

Table 6.6 reports on the molar conversions of the esterifications of geraniol with hexanoic acid and of cinnamyl alcohol with butyric acid obtained using these two biocatalysts under different conditions. In order to exclude possible adsorption of reagents and/or products on the biocatalysts, a procedure of extensive rinsing of the biocatalysts was applied and the hquid phases were analyzed by high-performance liquid chromatography. No appreciable presence of products nor reagents was observed. The effective achievement of the equilibrium was confirmed in all cases by the addition of further fresh biocatalyst after the reactions stopped. 

Figure 6.5 Variation in the RH measured during the esterification reaction of butyric acid with different alcohols cinnamyl alcohol ( ), 1-phenyl-1-butanol ( ), and Z-L-Ser-OBzl (A). Experimental conditions 2 ml of toluene, 20 mg of lyophilized mycelia, and 50mM equimolar substrates in a 6ml sealed vial.

As already indicated, a special problem with esters is their preparation from two natural precursor molecules by a chemical ester synthesis. Such products have to be labelled nature-identical. For an interesting positional H-NMR study on ethyl butyrate from enzymatic esterification of beet ethanol with butyric acid from milk see [317]. Another chance to detect a corresponding adulteration would be a positional carbon and oxygen isotope analysis of the ester components. Isotope effects on the esterification reaction in question seem to influence characteristically the 8-values of the atoms involved, and hence form a basis for the origin assignment of these compounds (for further details see 6.2.2.4.4). 

Stock solutions of butyric acid (150 mM) and butanol (150 mM) were prepared in n-heptane. Experiments were set up in 250-ml flasks containing 20 ml of stock solution, 1 g of molecular sieve 4A, and 0.3 g of the immobilized CALB or 0.012 g of Novozyme 435. The flasks were kept at 30 °C under agitation at 150 rpm for 24 h [31]. The consumption of butyric acid was measured by titration with 0.02 M NaOH and using phenolphthalem as indicator. The total acid content before reaction was determined by titration of a blank sample, without enzyme. The esterification 3tield was calculated Ifom the decrease in butyric acid concentration after 24 h of reaction. 

Immobilized enzyme stability was assayed by using 0.3 g of the immobilized CALB on fiber or 0.012 g of Novozyme 435 in successive batches of butyl butyrate synthesis. Assay conditions were the same as described for the determination of esterification yield. At the end of each batch, the immobilized lipase was removed from the reaction medium and rinsed with hexane (20 ml) to extract any substrate or product eventually retained in the matrix. After 1 h at room temperature, the immobilized derivative was introduced into a fresh medium. The residual conversion is given as percentage of initial conversion of butyric acid (first cycle of synthesis) under standard conditions (described in Esterification Yield Butyl Butyrate Synthesis ). 

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