Dimethyl acetal, formation with

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

A related [l,2]-rearrangement was described by Schlenk and Bergman in 1928. As shown below, reduction of benzophenone dimethyl acetal (6) with metallic sodium led to the formation of diphenyl methyl carbinol (8), presumably via intermediate organosodium species 7. ... 

DMSO can be boiled under reflux for long periods largely unchanged (3.7% of volatile decomposition products after 72 h) but under air or O2 in a sealed tube, kept just below the boiling point (189 C) for 68 h, it is completely transformed into paraformaldehyde, dimethyl sulphide, and bis(methylthio)methane, water, and dimethyl disulphide." " Peroxides catalyse the decomposition, as does MeSOjH." " The formaldehyde formed in this way can be used for in situ methylene acetal formation with oxidation products of alcohols and diols." Reduction of DMSO with Br2+HBr gives MezS, MeSOsH, and paraformaldehyde, while diphenyl sulphoxide is unchanged." ... 

Acid moieties include formic acid itself, formates and orthoesters, formamide, DMF dimethyl acetal and ethyl diethoxyacetate, acids, acid chlorides and anhydrides, the last including a rare [3,4-oxalate esters, 2-acyl or 2-ethoxycar-bonyl derivatives e.g. 180) are formed. 

The rates of both formation and hydrolysis of dimethyl acetals of -substituted benzaldehydes are substituent-dependent. Do you expect to increase or decrease with increasing electron-attracting capacity of the pam substituent Do you expect the Ahydroi to increase or decrease with the electron-attracting power of the substituent How do you expect K, the equilibrium constant for acetal formation, to vary with the nature of the substituent ... 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

In a situation where severe steric hindrance e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both lactone acetates. 

The second group of reactions is called vicinal difunctionalization. They embrace the C2 and C3 positions of the furan ring simultaneously. Thus, complex 3 (X = O, R = R = R = H) reacts with benzaldehyde dimethyl acetal to give 4H-furanium cation (the product of electrophile addition at C4), which experiences further attack by the methoxide group with formation of the acetal 8 (950M2861). This reaction is possible in the presence of the Lewis acid (BF3—OEt2). Reaction with methyl vinyl ketone in methanol, when run in identical conditions. 

Alkylation of allylic acetates (formates or chlorides) with the dimethyl malonate anion is catalyzed by sodium tricarbonyl(nitroso)iron90. The nucleophile attacks the less hindered site... 

Transformations of Methyl 5-0-Benzyl-2-0-methyl-/3-I)-glueofuranosidurono-6,3-lae-tone (86) to Dimethyl (Z,E)-2-Methoxy-5-(phenylmethoxy)-2,4-hexadienedioatevl (87). ( Elimination employing DBU b oxidation with silver oxide-sodium hydroxide followed by diazomethane esterification c acidic glycoside cleavage, oxidation by dimethyl sulfoxide-acetic anhydride with formation of 5-0-benzyl-2-0-methyI-D-glucaro-1,4 6,3-dilactone, elimination by using DBU, followed by short treatment with diazomethane d elimination by DBU with subsequent diazomethane esterification e sodium borohydride in hexamethylphosphoric triamide 1 catalytic oxidation followed by short treatment with diazomethane " dimethyl sulfoxide-sulfur trioxide-pyridine-triethylamine.150)... 

The product possesses a homoallylic stannane moiety, which can be utilized as a useful synthon for cyclopropane formation (Scheme 68). Upon treatment of the homoallylstannane with HI, destannative cyclization takes place to give cyclopropylmethylsilane.271,272 A Lewis acid-catalyzed reaction with benzaldehyde dimethyl acetal affords vinylcyclopropane.273... 

The latter reaction could be repeated ten times without loss of activity of Yb-XN-1010. Similar results were obtained with ytterbium(III) loaded Amberlyst 15W resin in a two-step one-pot procedure first involving the formation of the active dimethyl acetal from a benzaldehyde derivative which was followed by in situ protection of sucrose (Scheme 4.17) [100]. 

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). 

Figure 7 shows the results of methyl acetate carbonylation in the presence of water. Methanol and dimethyl ether were formed up to 250 C suggesting that hydrolysis of methyl acetate proceeded. With increasing reaction temperature, the yield of acetic acid increased remarkably, while those of methanol and dimethyl ether decreased gradually. Figure 8 shows the effects of partial pressures of methyl iodide, CO, and methyl acetate in the presence of water. The rate of acetic acid formation was 1.0 and 2.7 order with respect to methyl iodide and CO, respectively. Thus, the formation of acetic acid from methyl acetate is highly dependent on the partial pressure of CO. This suggests that acetic acid is formed by hydrolysis of acetic anhydride (Equation 6) which is formed from methyl acetate and CO rather than by direct hydrolysis of methyl acetate. 

Treatment of 2-amino-5-nitrothiobenzamide with iV,iV-dimethylformamide dimethyl acetal gives 2-amino-iV-((dimethylamino)methylene)-5-nitrobenzothioamide 191 in excellent yield <2004TL5913>. Cycloaddition reaction of 191 with DMAD results in formation of dimethyl 2-(2-amino-5-nitrophenyl)-4-(dimethylamino)-4//-l,3-thiazine-5,6-dicarboxylate 192 in low yield when R = H. This is caused by cycloreversion of thiazine 192 to give dimethyl 2-((dimethylamino)methylene)-3-thioxosuccinate 193 and 2-amino-5-nitrobenzonitrile 194 (Scheme 19). When W((dimethylamino)methylene)-2-(alkylamino)-5-nitrothiobenzamides 191 (R = Me, Bn) are reacted with DMAD, the expected 4//-l,3-thiazine-5,6-dicarboxylates 195 are produced as stable compounds. 

---