Acetals 2.2- dimethoxypropane

Fig. 13 HPLC of vitamin E. (A) Standards of vitamin E vitamers. Column, 5-p.m Supelcosil LC-Si (250 X 4.6-mm ID) mobile phase, isooctane/ethyl acetate (97.5 2.5), 1.6 ml/min fluorescence detection, excitation 290 nm, emission 330 nm. Peaks (1) a-tocopherol (2) a-tocotrienol (3) /3-tocopherol (4) y-tocopherol (5) /3-tocotrienol (6) y-tocotrienol (7) 5-tocopherol (8) 5-tocotrienol. (B) Saponified rice bran sample. Chromatographic conditions as in (A) except for mobile phase isooctane/ethyl acetate/2,2-dimethoxypropane (98.15 0.9 0.85 0.1). (From Ref. 228. AOCS Press.)...

With aldehydes, primary alcohols readily form acetals, RCH(OR )2. Acetone also forms acetals (often called ketals), (CH2)2C(OR)2, in an exothermic reaction, but the equiUbrium concentration is small at ambient temperature. However, the methyl acetal of acetone, 2,2-dimethoxypropane [77-76-9] was once made commercially by reaction with methanol at low temperature for use as a gasoline additive (5). Isopropenyl methyl ether [116-11-OJ, useful as a hydroxyl blocking agent in urethane and epoxy polymer chemistry (6), is obtained in good yield by thermal pyrolysis of 2,2-dimethoxypropane. With other primary, secondary, and tertiary alcohols, the equiUbrium is progressively less favorable to the formation of ketals, in that order. However, acetals of acetone with other primary and secondary alcohols, and of other ketones, can be made from 2,2-dimethoxypropane by transacetalation procedures (7,8). Because they hydroly2e extensively, ketals of primary and especially secondary alcohols are effective water scavengers. 

However, 17a,21-acetonides (103), as well as acetals of other ketones or aldehydes, can be easily prepared by acid-catalyzed exchange reaction with dimethoxypropane or other alkyl acetals in dimethylformamide or benzene. Enol etherification of the A -S-ketone also occurs with the former procedure. 

Preparation. The anhyd salt is prepd by treating the hexahydrate with a large excess of 2,2-dimethoxypropane. Two phases are obtained with most of the Ni perchlorate in the lower phase. After several hours a solid seps from this phase which is filtered off and dried to give Ni perchlorate contg ca 0.5% w (Ref 20). Caution On one occasion, in the use of this proc, a violent expln occurred when the mixt was heated above 65° (Ref 18). It has also been prepd by dissolving Ni oxide or carbonate in anhyd trifluoroacetic ac followed by addn of anhyd perchloric ac. The pptd solid is filtered off and dried in a vacuum to remove trifiuoro-acetic ac (Ref 12)... 

Dimethyl or diethyl acetals can be prepared by acid-catalyzed exchange with an acetal such as 2,2-dimethoxypropane or an orthoester.247... 

Isopropylidene acetals are convenient protecting groups in carbohydrate chemistry, particularly for the protection of 1,2- and 1,3-diols, and are readily formed by reaction of the diol with acetone or 2,2-dimethoxypropane under acidic conditions. Several protic and Lewis acids have been reported as catalysts for this purpose.98... 

Compound 35 has also been obtained51 from 32, by sequential debenzoylation, and acetalization with 2,2-dimethoxypropane. It has been used in the synthesis, in good overall yield, of versatile, ano-merically functionalized precursors of C-nucleosides having the d-arabino or the D-ribo configuration. 

The reaction of sucrose with a combination of 2,2-dimethoxy-propane-N,N-dimethylformamide-p-toluenesulfonic acid has been exploited to give various, interesting, cyclic acetal derivatives.32,83-85 This combination of reagents for acetonation is known to give strained, and otherwise inaccessible, acetals of monosaccharides.86-89 Treatment of sucrose with 2,2-dimethoxypropane in N,N-dimethyl-formamide in the presence of a catalytic proportion of p-toluenesul-fonic acid for 80 min at room temperature afforded a mixture containing 4,6-O-isopropylidenesucrose, 2,1 4,6-di-O-isopropyli-... 

Dimethoxypropane Acetone, dimethyl acetal (8) Propane, 2,2-dimethoxy-(9) (77-76-9)... 

L. Hough, A. C. Richardson, and L. A. W. Thelwall, Reaction of lactose with 2,2-dimethoxypropane. A tetra-acetal of novel structure, Carbohydr. Res., 75 (1979) C11-C12. 

Although one diastereomer 10 was largely favored, the product was obtained as a mixture of diastereomers, and the previously unreported minor diastereomer 11 was also characterized. The stereochemistry of the products was established by nuclear Overhauser effect (NOE) studies. A plausible mechanism assumes the intermediacy of an acetal, and its reaction with 2-methoxypropene generated from 2,2-dimethoxypropane [20]. In order to test this mechanism, the dimethyl acetal of salicylaldehyde was synthesized and reacted independently with both 2,2-dimethoxypropane and 2-methoxypropene. Indeed, both reactions gave the same products as those from the reaction of salicylaldehyde with 2,2-dimethoxypropane (Scheme 4). The condensation of salicylaldehyde and 2,2-dimethoxypropane was also carried out in CD3CN and reaction progress was followed by H NMR spectroscopy. This experiment also confirmed the formation of the acetal from salicylaldehyde (8 5.52, singlet, C//(OMe)2). 

Addition of 2,2-dimethoxypropane (76) to a solution of 1 in H2O at pH 10 quickly yielded the hydrolysis products (acetone and methanol). To examine the reaction scope, various alkyl acetals and ketals were screened (Table 7.9). The hydrolysis reactions were screened by mild heating (50 °C) of 5 mol.% of 1 with respect to the acetal substrate at pH 10 in H2O. Smaller substrates, which are able to fit into the cavity of 1, are readily hydrolyzed. However, larger substrates, such as 2,2-dimethox-... 

The hydrated chloride, bromide and iodide (Table 9) are soluble in ethanol, butanol and other organic solvents, but in many systems traces of water cause oxidation, hydrolysis or failure to complex with weak donor ligands. Water can be avoided by dissolving the metal in THF, ethanol or diethyl ether through which hydrogen chloride is bubbled.24,74 75 It is also possible to dissolve or suspend in organic solvents the anhydrous acetate or the halides CrX2 (Table 9), and dehydration of the hydrated halides with 2,3-dimethoxypropane in ethanol, followed by vacuum removal of the liquid, produces mixed alcoholates suitable for use in water-free conditions.76 Triethyl orthoformate may be used similarly. 

The second example concerns the study of acetonation of o-mannose (see Scheme 8) and allows a clear distinction between the use of 2,2-dimethoxypropane and 2-methoxy-propene. Thus, whereas D-matmose gives 2,3 5,6-di-0-isopropylidene-D-mannofuranose 5 by reaction of the free sugar with acetone [5,6] as well as with 2,2-dimethoxypropane [96], the major compound (more than 85%) obtained with 2-methoxypropene is 4,6-0-isopropylidene-D-mannopyranose 6 [52]. Once again, a confirmation of the better stability of furanoid acetals in this series is given by the selective hydrolysis of the 2,3 4,6-di-O-isopropylidene-D-mannopyranose 7 (by-product of the preceding reaction or quantitatively obtained by action of 2-methoxypropene on acetal 6), witch gives the furanoid monoacetal 8. Actually, the pyranoid monoacetal 9 can be easily prepared as soon as the anomeric hydroxyl group is protected by acetylation [52]. 

The investigation of various conditions for the reaction of 2,2-dimethoxypropane has been conducted on several disaccharides [37]. The nature of the acetals thus obtained (mono- or multiacetals and pyranosylpyranose or pytanosylacyclic hexose forms of the protected disaccharide) depends largely on the temperature (room temperature, 40°C, 80°C), the solvent (DMF or 1,4-dioxane), and the amount of the acid catalyst that are chosen for the procedure. As a specific example, the synthesis of a tetraacetal of maltose is given here. 

Shin and Godber (228) used a silica column and a mobile phase composed mainly of isooctane and small amounts of ethyl acetate, acetic acid, and 2,2-dimethoxypropane. The acetic acid component reduced retention times of the late-eluting E vitamers, presumably by competing with water and polar material for binding to silanol groups on the silica surface. 2,2-Dimethoxy-propane reacts with water to form acetone and methanol, and its inclusion stabilized retention times and reduced the need for column regeneration. Chromatograms of vitamin E vitamers in a standard solution and in a saponified rice bran sample are shown in Fig. 13. 

Dimethoxypropane (18) was selected for acetal formation. Trans-ucetali/ation with the diol releases two equivalents of methanol, which results in a positive entropy effect. 

An unsuccessful attempt was next made to simplify the problem of purifying the product by using dioxane as the extracting solvent with only enough benzaldehyde for solvolysis. Finally, on the assumption that an acetal should be as effective in transacetalization as an aldehyde or ketone, the benzaldehyde was replaced by 2,2-dimethoxypropane. In several experiments the hydrogen chloride was replaced by -toluenesulfonic acid also, dimethyl sulfoxide was tried instead of dioxane. All these experiments are summarized in Table I, and they lead to the following conclusions ... 

Acetals such as dimethoxypropane and diethoxypropane with hydrogen chloride in dioxane extract lignin from wood much more rapidly than methanol, acetone, or water. When the extraction is performed in a Soxhlet extractor, unusually high yields of lignin are obtained. 

Acid-catalyzed iV,0-acetal reaction of iV-BOC protected 2-amino-1,4-butanediol 208 with dimethoxypropane gave only moderate yields of 209 because of concurrent six- and five-membered ring formation (Scheme 59) <20050L1423>. 

Synthesis of acetonides can also be performed using 2-methoxypropene instead of 2,2-dimethoxypropane <20050L5011> however, 4,5-dihydro-l,3-dioxepins, such as 216 (Scheme 61), can only be obtained by direct acetalization or transacetalization with special substrates. 

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