Alcohols methoxymethylation

Displacement of a volatile with a nonvolatile alcohol is an important reaction for curing paint films with amino cross-linkers and amino resias on textile fabrics or paper. FoUowiag is an example of a methoxymethyl group on an amino resia reacting with a hydroxyl group of a polymer chain. 

Fraaije MW, WJH van Berkel (1997) Catalytic mechanism of the oxidative demethylation of 4-(methoxymethyl)phenol by vanillyl-alcohol oxidase. Evidence for formation of a /7-quinone intermediate. /Sio/ Chem 272 18111-18116. 

The methoxymethyl (MOM) and (3-methoxyethoxymethyl (MEM) groups are used to protect alcohols and phenols as formaldehyde acetals. These groups are normally introduced by reaction of an alkali metal salt of the alcohol with methoxymethyl chloride or (3-methoxyethoxymethyl chloride.157... 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

Methoxymethylation of alcohols is generally achieved through alkylation with chloromethyl methyl ether. The procedure described here for the preparation of Bu3SnCH20CH20CH3 avoids the use of the highly toxic chloromethyl ether by employing an acid-catalyzed acetal exchange reaction with dimethoxymethane for the... 

In some instances, treatment of polyfunctional benzylic alcohols with acid in the presence of organosilicon hydrides causes multiple functional group transformations to occur simultaneously. This phenomenon is illustrated by the reduction of the secondary benzylic alcohol function and concomitant loss of the methoxymethyl protecting group of 2-(l-hydroxydecyl)-5-methoxy-l-(methoxy-methyleneoxy)naphthalene upon treatment with Et3SiH/TFA in dichloromethane (Eq. 26).167... 

Recently, poly(vinyl alcohol)-isocyanate reactions have been run successfully in dimethylsulfoxide solutions by several lab- oratories, including ours. While there are reports of solvent derived products from the reactions of isocyanates in DMSO (60), these reactions do not seem to pose a problem in the reaction with poly(vinyl alcohol). This solvent has been used to react PVA with methoxymethyl isocyanate (61.62) and a series of isocyanates including methyl, ethyl, isopropyl, phenyl and 1-naphthyl (63). This reaction is illustrated in Equation 17 where R is... 

Methoxyethanol, see Methyl cellosolve 2-Methoxyethanol acetate, see Methyl cellosolve acetate 2-Methoxyethyl acetate, see Methyl cellosolve acetate 2-Methoxyethyl alcohol, see Methyl cellosolve 2-Methoxyethyl ethanoate, see Methyl cellosolve acetate Methoxyhydroxyethane, see Methyl cellosolve Methoxymethyl methyl ether, see Methylal 4-Methoxyphenylamine, see p-Anisidine... 

Birch reduction-alkylation of (2S)-2-methoxymethyl-l-(2-phenylbenzoyl)pyrrolidine (1) gives products 2 in high diastereoselectivities29. In contrast to the previous examples, only one double bond remains in the product (if one equivalent of rm-butyl alcohol is used as proton donor). Formally this procedure is a stereoselective cis addition, and is thus particularly useful. Thus, two stereogenic centers are created in the same reaction step with high diastereoselectivities. Subsequent hydrolysis furnishes acids, whereas reaction with methyllithium yields chiral ketones29. 

The hydroxy groups of pyrrolizidine amino-alcohols are readily replaced by chlorine atoms upon treatment with thionyl chloride (see, e.g., refs. 101 and 103). In this reaction, the allylic hydroxyl group is more reactive and can be selectively replaced by chlorine.79 In some particular cases, methoxyl groups can also be substituted for halogen e.g., l/3-methoxymethyl-8a-pyrrolizidine, when treated with hydro-bromic acid, gives rise to the corresponding bromo derivative.104... 

The (R)-enantiomer of (242) has also been prepared and used as a chiral auxiliary in an enantioselective aldol synthesis of (+)-(S )-gingerol (79CB3703). (R )-Glutamic acid (246) was thus converted into (i )-pyroglutamic acid by simply heating in water. Conversion of (247) to its methyl ester and LAH reduction delivered alcohol (248). Ethyl nitrite treatment of (248) gave nitrosoamine (249), which was methylated to furnish (250). Exposure of (250) to LAH completed the synthesis of the required chiral auxiliary RAMP [(R)- l-amino-2-(methoxymethyl)pyrrolidine]. The hydrazone (252), derived from RAMP and acetone, was... 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

Again, the activity of Nafion-H in the above protection processes (transformation of alcohols to THP ethers672 and methoxymethyl ethers679) is lower, and consequently, longer reaction times and elevated temperatures are required to achieve yields comparable to those over Nafion nanocomposites. Obviously, this is due to the low specific surface area and low accessibility of the active sites of Nafion-H as compared with Nafion SAC-13. 

Quenching of the ion 36 with methanol at — 78° C gives the 2-methoxymethyl-butadiene complex (37). Alcohol 38, when protonated at low temperature, first forms cation 39, with an anti-methyl substituent, which rearranges to 40 on warming to room temperature [Eq. (23)]. Studies of trimethyl derivatives gave... 

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