Purification, general procedures acetals

General Procedure for the Hydroformylation/Carbonyl ene Reaction/O,O-acetal Forma-tion/Dehydration. Synthesis of Chromane Derivatives. A solution of the substrate (1 eq) RhCl(PPh3)3 (1 mol %) and PPh3 (3 mol %) in dry dioxane was heated for 70 h to 120 °C und an atmosphere of CO/H2 (1 1, 100 bar). The crude product was filtered through basic alumina (eluated with MTBE). After evaporation of the solvent further purification by column chromatography (silica, PE/MTBE) furnished the title compounds. 

As a general procedure if the olefin is impure, the oxymercura-tion-reduction process may include an olefin purification step. Alternatively, this process may be used to purify the olefin for other purposes. - In such cases, acetone is substituted for ether and, after oxymercuration for the same length of time as suggested above, the solution is poured with stirring into two volumes of water containing one equivalent each of sodium bicarbonate and sodium chloride. The mercury derivative is filtered, recrystallized from ethanol-water, ether, dioxane, or ethyl acetate-heptane and then either reduced as described above (in 70-80% yield) to produce pure alcohol, or deoxy-mercurated with cold 6N HCl, with ethereal lithium aluminum hydride (added cautiously), or high concentrations of alkali halides - to produce the pure olefin. 

General procedure. Nitriles from carboxamides [1144] A solution of the carboxamide (5 mmol) in dry benzene (50 mL), containing silver oxide (1.8 g, 7.7 mmol) and powdered 4 A molecular sieves (5.0 g) was stirred in the dark at 25 °C for 12 h. lo-doethane (0.86 g, 0.44 mL, 5.5 mmol) was then added, and the mixture was heated to reflux under argon for 17 h. The cooled solution was then Altered (Celite) and the filtrate was concentrated under reduced pressure. Purification was accomplished by chromatography on silica gel, eluting with hexane and ethyl acetate in varying proportions. 

Scheme 20), these acetals could readily be converted into isofiavones. Unfortunately, very low yields of rearrangement products were obtained using thallium(III) acetate, and separation and purification of acetals such as (XXXIV) was extremely tedious. Reaction of chalcones with TTN, on the other hand, is generally complete within a few hours at room temperature 95), and Farkas et al. (J75) have developed the Ollis procedure into a simple method for the preparation of isofiavones (Scheme 21). 

All solvents used for general applications were of reagent grade. For special purposes, purification of solvents was effected using standard procedures. All other reagents were used as supplied commercially except as noted. A solution of chloromethyl methyl ether (6 mmole/mL) in methyl acetate was prepared by adding acetyl chloride (141.2 g, 1.96 mol) to a mixture of dimethoxy methane (180 mL, 2.02 mol) and anhydrous methanol (5.0 mL, 0.12 mol).20 The solution was diluted with 300 mL of 1,1,2,2-tetrachloroethane and used as a stock solution for the chloromethylation experiments. 

The procedure illustrates a general method for the preparation of ketene S,N-acetals via thioamides and their crystalline quaternary iodides some other examples are shown in Table I. 2,2-Dialkyl-substituted ketene S,N-acetals cannot be prepared by this method because the nature of the products makes rigorous purification impractical. Ketene S,N-acctals are useful starting materials for many syntheses.11,13 15... 

Quinazoline-4(3//)-thiones 13 are prepared in a very simple, one-step synthesis by treatment of 2-[(ethoxymethylene)amino] derivatives 12 with alcoholic sodium hydrosulfide. Numerous other hetero-fused pyrimidinethiones are also available by this procedure (Method Cyclization proceeds uniformly in very high yields, generally in excess of 90%. In some cases, since isolation and purification of (ethoxymethylene)amino derivatives results in the lowering of the overall yield, the one-step procedure, consisting of treatment of a 2-aminonitrile 11, either with a 1 1 mixture of triethyl orthofoimate and acetic anhydride or with triethyl orthoformate alone, to give an intermediate ethoxymethyleneamino derivative which, without isolation, is treated with an ethanolic solution of sodium hydrosulfide, is preferred for preparative purposes (Method B). In a few cases, conversion of the 2-aminonitrile to a 2-aminothioamide followed by cyclization with triethyl orthoformate (see p 47) competes favorably with the above procedure. 

When treated with concentrated alkali, acetoacetic ester is converted into two moles of sodium acetate, (a) Outline all steps in a likely mechanism for this reaction. (Hint See Sec. 21.11 and Problem 5.8, p. 170.) (b) Substituted acetoacetic esters also undergo this reaction. Outline the steps in a general synthetic route from acetoacetic ester to carboxylic acids, (c) Outline the steps in the synthesis of 2-hexanone via acetoacetic ester. What acids will be formed as by-products Outline a procedure for purification of the desired ketone. (Remember that the alkylation is carried out in alcohol that NaBr is formed that aqueous base is used for hydrolysis and that ethyl alcohol is a product of the hydrolysis.)... 

Separation and Assay. Procedures for the separation, purification, and assay of carotenoids and retinoids by h.p.l.c., g.c., and g.c.-m.s. are given in an extensive article." Another, general, review includes information on the h.p.l.c. separation of retinoids.A particularly useful method has been developed for resolution and analysis of some carotenoid optical isomers.For example, (3R,3 R)-, (3S,3 S)-, and (3/ ,3 5)-astaxanthin were converted into the diastereomeric (-)-camphanic acid diesters, which were separated by h.p.l.c. This procedure has been used to analyse the isomeric composition of a natural astaxanthin sample. An h.p.l.c. procedure for separation of a-, P-, and y-carotenes (173)—(175) and lycopene (176) has been described." Several papers describe methods for the h.p.l.c. separation and purification of various retinal and retinol isomers and derivatives.A procedure for the preparative t.l.c. of oxidation products of retinyl acetate has been described,and a competitive protein-binding radioassay for retinoic has been reported. 

For example, reaction of methoxyallene with an allyHc alcohol under palladium catalysis yielded unsymmetrical mixed acetal 22a in 74% yield (Scheme 5(a)). Treatment of 22a with 10 mol% of Grubbs second generation catalyst 3, followed by add promoted aromatization yielded fiiran 12a in 79% isolated yield for the one-pot protocol. However, the nonpolar furan products were usually contaminated with (nonpolar) phosphine residues from the catalyst, which made the purification step problematic. Therefore, it was generally advantageous to purify the dihydrofuran intermediate prior to the aromatization step. In a similar manner to furans, allyftc sulfonamide 21a was converted to the N,0-acetal 23a in 63% yield under palladium catalysis. Then RCM followed by aromatization proceeded smoothly to provide the desired N-protected pyrrole 13a in 61% yield over two steps (Scheme 5(b)). This procedure can also be applied... 

Liquid-liquid partitioning cleanup is generally carried out at alkaline conditions using ethyl acetate, ethyl acetate-tert-butanol mixture, diethyl ether, or tert-butyl methyl ether/n-butanol as extraction solvents. " The organic extracts are then either concentrated to dryness or repartitioned with dilute acid to facilitate back extraction of the analytes into the acidic solution. A literature survey shows that liquid-liquid partitioning cleanup resulted in good recoveries of substituted anilines such as clenbuterol, " but it was less effective for more polar compounds such as salbutamol. Diphasic dialysis can be also used for purification of the primary sample extract. This procedure was only applied in the determination of clenbuterol residues in liver using tert-butyl methyl ether as the extraction solvent. ... 

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