Chromatography and Recrystallization

Most boronic acids can be recrystallized with ease. The choice of recrystallization solvent, however, greatly affects the relative proportions of free boronic acid and its corresponding anhydrides in the purified solid. Santucci and Gihnan found that acids are usually obtained from aqueous solutions (i.e. water or aqueous ethanol), and anhydrides predominate when non-polar recrystallization solvents like ethylene dichlo- 

---

The reactions of isoselenocyanates with carbodiimides in refluxing hexane afford l,3-selenazetidine-2,4-diimines 33 by a [2+2] cycloaddition in moderate to good yields (Scheme 12 and Table 4) <2005HCA766>. These compounds can be purified by silica gel chromatography and recrystallization. All products 33 are stable and can be stored at room temperature. 

The product 144 has 98.8% radiochemical purity after chromatography and recrystallization. No kinetic tritium isotope effect and tritium exchange with the solvent in the last two syntheses has been studied. 

Flash chromatography and recrystallization gave the desired SK F 214 in 17% final purified radiochemical yield with a specific activity of 16 mCi mmol -1 and radiochemical and chemical purities >99%. No change of radiopurity was found in a solid sample of 214 stored under argon at — 25 °C during 6 months. 

To prepare the enantiomerically pure iron acyl complex (R)-(39), a precursor diastereomeric menthoxyaUcyl complex was resolved and then manipulated (Scheme 14). More recently resolution of the chiral-at-metal acyl complexes themselves was achieved, and this has become the basis for a commercial preparation of the iron acyl developed for use as a chiral auxiliary (see below). Cationic iron complex (43) was treated with potassium L-mentholate to produce diastereomeric esters (44) that were not isolated but were reacted with LiBr/MeLi (Scheme 15). After chromatography and recrystallization the enantiomerically pure ironacyl complex (5 )-(39a) was obtained. It was suggested that only one diastereomeric ester can react (with inversion of configuration at iron, as shown) with the methyl nucleophile the unreactive diastereomer suffers from severe steric congestion about the electrophilic CO ligand. 

Recrystallization apparently leads to considerable loss of material without appreciable gain in purity. From a 5.1-g. sample of the crude mixture subjected to both chromatography and recrystallization the checkers isolated 0.72 g. of cis isomer, m.p. 163.4 to 164.0 , and 2.25 g. of trans isomer, m.p. 169.2 to 169.6°. 

Purity of the final product. As the process uses molecular precursors rather than bulk materials, standard purification techniques such as distillation, sublimation, chromatography, and recrystallization can be applied. 

A mixture of A W-dimethylacetamide dimethyl acetal (1.33 g, 10 mmol) and the anhyd cyclic amine (20 mmol) was heated to 190 rC for 5 h, a slow stream of dry N2 being bubbled through the solution. After cooling, 4-benzoyl-6-chloropyridazin-3-amine (234 mg, 1 mmol) was added. The mixture was heated to 120 "C for 30 min, then it was evaporated in vacuo. The products were purified by column chromatography and recrystallized (EtOAc). 

REDUCTIVE DIMERIZATION OF CYCLOPROPYLTRIPHENYLSILANE. A solution of 1.10 g (3.6 mmol) of the cyclopropyltriphenylsilane in 30 mL of THF and 30 mg (4.6 mg-at) of lithium pieces, after stirring at -78 °C for 20 h and hydrolytic workup, produced an almost quantitative yield of 4,4 -bis(cyclo-propyl(diphenyl)silyl)-l,l, 4,4 -tetrahydrobiphenyl, which after column chromatography and recrystallization from ethyl ether melted at 145-151 °C (22). 

Treatment of 123 with thionyl chloride furnishes acid chloride 227 in high yield. By the route outlined in Scheme 33, a variety of 6-deoxy-L-hexoses can be prepared from common intermediate 230 [48]. This intermediate is obtained as an anomeric mixture (2 1 a/j5), where the desired a-anomer is separated by column chromatography and recrystallization. Reduction of the olefin and ketone gives optically pure methyl a-L-amicetoside (231). 

The synthesis of methyl 7-aminocoumarin-4-carboxylate (93) was reported by heating m-aminophenol (84) (R = H, R = NH2) with dimethyloxalacetate (92) at 130 °C for 2h (84CPB3926). The yield of coumarin under such conditions was variable, sometimes low and accompanied by colored impurties that were very difficult to eliminate, even by column chromatography and recrystallization. This procedure in a focused MW reactor gave 93 in a similar yield (39%), but in less time (85min). Moreover, a better yield (44%) and a shorter time (50 min) were achieved by irradiation of a mixture of 84 and 92, adsorbed on graphite (Scheme 18) (01TL2791). 

Since the original sample of osladin and spectral data were not available, we isolated the rhizomal sweet principle of P. vulgare from plants collected in the southern part of Germany by Professors Y. Asakawa and H. Becker. Sweet components of the fern were extracted by ethanol. Successive chromatography and recrystallizations afforded pure sweet compound as colorless crystals (0.02% isolated yield). Since the sweet compound has a mp of 202-204 C (lit. 201-203 °C) and a molecular formula C45H74O17 suggested from HRMS (FAB), this is the same compound, osladin, which was isolated by Jizba and Herout. Both and NMR spectra of the natural osladin were not identical with those of synthetic 2. Thus, the structure of real osladin differs from that of 2. 

A solution of 6.51 g (32.5 mmol) of anisoin and 9.30 g (34.1 mmol) of 4-bro-mobenzamide in 75 mL of 1,4-dioxane was treated with 0.5 mL of cone, sulfuric acid and heated at reflux for 18 h. Neutral workup provided a cmde product which was purified by flash chromatography and recrystallized from ethyl acetate to give 2-(4-bromophenyl)-4,5-bis-(4-methoxyphenyl)oxazole, 8.78 g (62%) m.p. 168-170 C. 

The techniques of separation and purification most commonly employed are solvent extraction, distillation, chromatography and recrystallization. More than one of these techniques may be needed. 

Purification of the oligomers was achieved by repeated chromatography and recrystallization. In the case of the higher members, extraction of the crude material and fractional sublimation gave the best results. The final purification of all compounds in this series was achieved by repeated fractional sublimation in a glass tube with temperature gradient. 

---