Work-up procedure

The reactions described so far can be considered as alkylation, alkenylation, or alkynylation reactions. In principle all polar reactions in syntheses, which produce monofunctional carbon compounds, proceed in the same way a carbanion reacts with an electropositive carbon atom, and the activating groups (e.g. metals, boron, phosphorus) of the carbanion are lost in the work-up procedures. We now turn to reactions, in which the hetero atoms of both the acceptor and donor synthons are kept in a difunctional reaction produa. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

On the other hand, a lot of material is lost in the chromatography and work-up procedures ( 40%), and the analytical data provided are not very convincing, either (except for TLC). 

The time necessary for completion of the reaction may vary from 0.5 to 4 hours, depending on the actual activity of the alumina. The progress of conversion should be monitored by infrared analysis of a concentrated sample of the solution. Stirring should be continued for 15 minutes after the nitroso band at 1540 cm. has disappeared. A strong diazo band at about 2100 cm. will then be present. The carbonyl band at 1750 cm. initially due to nitrosocarbamate, will usually not disappear completely during the reaction, because some diethyl carbonate is formed in addition to carbon dioxide and ethanol. Diethyl carbonate is removed during the work-up procedure. 

In a typical experiment, triethylene glycol was treated with two equivalents of sodium toluenesulfonamide in dry DMF solution. After 6 h at reflux, the solution was distilled and product obtained by a standard work-up procedure. By this procedure, 9 was obtained in about 10% yield. The transformation is illustrated below as Eq. (4.10). Note also that Vogtle and his coworkers have also utilized phthalimide as a source of nitrogen in the preparation of such azacrown precursors as H2N(CH2CH2 0)2CH2CH2NH2 In such reactions, a standard hydrazine cleavage was used to remove the phthaloyl residue. 

Reduction of linearly conjugated 4,6-dien-3-ones with lithium-ammonia yields either 5-en-3-ones or 4-en-3-ones depending upon the work-up procedure. Protonation of the dienyl carbanion intermediate (58) occurs at C-7 to give ultimately the enolate ion (59) kinetic protonation of (59) occurs largely at C-4 to give the 5-en-3-one (60). ... 

Another reagent system that has been recently employed in the Paal synthesis of thiophenes is the combination of bis(trialkyltin)- or bis(triaryltin) sulfides with boron trichloride. Known as the Steliou reagent,it has been utilized in the transformation of 1,4-diketone 11 to thiophene 12. Higher yields are obtained in shorter reaction times in contrast to the use of Lawesson s reagent. Additionally, others have noted the relative ease of the work-up procedure using the Steliou conditions, and the fact that the tributyltinchloride byproduct of the reaction is reusable. Similarly, the combination of the bis(trimethylsilyl)sulfide has been used in conjunction with trimethylsilyltriflate for the preparation of thiophenes in an analogous manner. ... 

The precise structure of the zirconium catalyst was examined by NMR analysis. When Zr(Ot-Bu)4 (1 equiv), 8b (2 equiv), and NMI (3 equiv.) were combined in benzene-dg at 23 °C, two independent species which were assigned to a new zirconium catalyst and free 8b were observed. Although the signals of free 8b were still observed when Zr(Ot-Bu)4 (1 equiv), 8b (1 equiv), and NMI (3 equiv.) were stirred at 23 °C, only the signals assigned to the new zirconium catalyst were detected when the mixture was stirred at 80 °C for 2.5 h. These results indicated the formation of 9b as the new zirconium catalyst. The structure was also supported by an experiment in which Zr(Ot-Bu)4 (0.2 equiv), 8a (0.2 equiv), NMI (0.6 equiv), and MS 3 A were combined in benzene and the mixture was stirred for 2.5 h at 80 °C (formation of 9a). Imine Id (1 equiv.) and 7a (1.2 equiv.) were then added to the catalyst solution, and the mixture was stirred for 48 h at 23 °C. After the same work-up procedures as described above, the desired piperidine derivative was obtained in >98% yield with 89% ee, values comparable with those... 

Cyclohexanone undergoes dicarboxylation when treated with a 10-fold excess of MMC. When 2 g (0.02 mole) of cyclohexanone is treated with 100 ml of approx. 2 M MMC at 120-130° for 6 hours, the usual work-up procedure gives about 50% yield of 2,6-cyclohexanonedicarboxylic acid, mp 123° after recrystallization from ether-petroleum ether. 

This work-up procedure applies only when the crude product can be crystallized from the reaction mixture. If the product is partly soluble in the reaction medium or if it separates as a gum, an extraction procedure is employed. 

The initially formed tetra-alkylferrate(II) represents the reactive intermediate in both reactions that undergoes a carboferration of the triple bond in eq. 2, Scheme 29. Transmetallation from Fe to Mg yields a vinyl-magnesium species, which liberates the desired olefin upon hydrolysis within the acidic work-up procedure. In the above two reactions, a competing p-hydride elimination from the ferrate yields the unreactive Fe-H species and hence is considered to be the deactivation step in the catalytic cycle. 

Subsequently, it has been found that 44 can be incorporated into DNA oligomers intact using alternative reagents and work-up procedures. However, the oligomers produced contain a 1 1 mixture of 44 45... 

The well documented synthetic method for 37 is chlorination of cyclopropyl-methylketone followed by base treatment [29]. However, this method did not provide a suitable impurity profile. The most convenient and suitable method we found was the one-step synthesis from 5-chloro-l-pentyne (49) by addition of 2equiv of base, as shown in Scheme 1.18 [21, 30]. Two major impurities, starting material 49 and reduced pentyne, had to be controlled below 0.2% each in the final bulk of 37, to ensure the final purity of Efavirenz . Acetylene 37 was isolated by distillation after standard work-up procedure. 

The key Pd-catalyzed coupling step to the indole was optimized by judicious choice of the protection group on 3-butyn-l-ol, screening of different reaction parameters such as bases and additives, and implementing a fine-tuned, yet practical work-up procedure. Tryptophol 27 was isolated in 76-82% yield by crystallization. 

The working-up procedure of the reaction mixtures of the 2-benzyl-l-benzosuberone was the catalyst filtration and the removal of the solvent in vacuum. The residue was dissolved in dichloromethane and extracted with 5 % HC1 and distilled water. The organic phase was separated and dried over Na2S04. After filtration, the solvent was removed in vacuum. 

There are two approaches to synthesizing hydrophilic carotenoids (1) appending a hydrophilic group to the carotenoid scaffold (Foss et al. 2006a) or (2) joining a carotenoid to a hydrophilic compound, Scheme 3.3 (Foss et al. 2003). Whereas the Scheme 3.3 intuitively explains the difference, these techniques cannot be clearly separated in praxis the distinction may appear more emotional than conceptual. Both methods are habitually hampered by low yields, find their limits in the availability of functionalized carotenoids, and cause problems in the work-up procedure due to the amphiphilic character of the products. 

Herein, the stereogenic center in 2-12 controls the stereochemistry in the way that the Michael addition occurs from the less-hindered a-face of the enolate to the si-side of the crotonate 2-13 according to transition structure 2-16. The second Michael addition occurs from the same face, again under chelation control, followed by an axial protonahon of the formed enolate to give the cis-compound 2-14a. It should be noted that after the usual aqueous work-up procedure an inseparable... 

Typical VNS consists of a reaction between a nitroarene such as nitrobenzene and a carbanion containing a leaving group X at the carbanionic center. In the first step, addition of the carbanion to the nitroarene results in the formation of o-adduct, which undergoes P-elimination of HX to form the nitrobenzylic carbanion, which is subsequently protonated during the work-up procedure (Scheme 9.7). 

In a synthesis similar to that depicted in Scheme 54, aminoesters 344 dissolved in DMF are treated with POCI3 and heated at 50-60 °C for 2h. The simple work-up procedure involves pouring into ice-water, neutralization with NaOH and separation of the precipitate by fdtration to afford amidines 345 in 66-86% yield (Equation 11). Some of the obtained amidines exhibit selective antibacterial activity <2003SC3969>. 

For model reactions, we chose the aromatic substitution of aryl halides with nucleophiles such as phenolates or amines. The reaction parameters particularly focused upon were reaction time, selectivity, work-up procedure, and overall processing time. 

Two different typical work-up procedures were applied in order to demonstrate the influence on the yield. 

Compound 51 was found to be unstable and difficult to purify, as described in the literature [93—95]. Therefore, 51 was not isolated, but was instead converted to the stable pinacol 1-acetamido-l-hexylboronate derivative 52. However, the acylated derivative 52 could not be purified by column chromatography as it was destroyed on silica gel and partially decomposed on alumina. Fortunately, we found that it dissolves in basic aqueous solution (pH > 11) and can then be extracted into diethyl ether when the pH of the aqueous layer is 5—6. Finally, pure 52 was obtained by repeated washing with weak acids and bases. It should be mentioned here that exposure to a strongly acidic solution, which also dissolves compound 51, results in its decomposition. Compared with other routes, the present two-step method involves mild reaction conditions (THF, ambient temperature) and a simple work-up procedure. It should prove very useful in providing an alternative access to a-aminoboronic esters, an important class of inhibitors of serine proteases. 

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