Diols mono-alkylation

A. Alkaline Hydrolysis VI 1,2-Diol Mono alkyl- and Momoaiyl ... 

The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical or symmetrical ethers.The reaction can also be carried out with aromatic R, although C-alkylation is sometimes a side reaction (see p. 515). The normal method involves treatment of the halide with alkoxide or aroxide ion prepared from an alcohol or phenol, although methylation using dimethyl carbonate has been reported. It is also possible to mix the halide and alcohol or phenol directly with CS2CO3 in acetonitrile, or with solid KOH in Me2SO. The reaction can also be carried out in a dry medium,on zeolite-or neat or in solvents using microwave irradiation. Williamson ether synthesis in ionic liquids has also been reported. The reaction is not successful for tertiary R (because of elimination), and low yields are often obtained with secondary R. Mono-ethers can be formed from diols and alkyl halides. Many other... 

Selective activation of hydroxyl groups by the stannylation procedure is an established practice to efficiently manipulate diols and polyols [53, 54]. Among the various reagents and methods, activation through dialkylstannylene acetals is noteworthy. This two-step protection method involves the conversion of dihydroxy substrates into cyclic dialkyl dioxastan-nanes which, in turn, are treated with suitable nucleophiles, to regioselectively afford the corresponding mono alkyl, silyl or acyl derivatives under neutral conditions. 

In 2003, our group developed a new type of protonation reagent involving mono-alkylated l,2-diarylethane-l,2-diols as ligands (Fig. 12) [55]. A model for understanding the enantioselectivity was proposed based on the crystallographic structure of this LBA catalyst. 

A search for the structural changes expected in the early stages of a classical 1,2-alkyl shift was also fruitless. A series of mono-substituted / ra 5-cyclohexane-l,2-diols [104], which undergo the pinacol rearrangement... 

Evidence of the formation of mono-M-octylphthalatc and phthalate ester metabolites has been shown in in vitro studies. The appearance of mono-w-octylphthalatc was observed with preparations of human small intestine, rat liver and intestine, ferret liver and intestine, and baboon liver and intestine (Lake et al. 1977). However, the amount of phthalic acid and other metabolites in these preparations was either minimal or not detected. The study authors concluded that di-ra-octylphthalate is probably absorbed primarily as mono- -octylphthalate (Lake et al. 1977). An in vitro study reported the formation of five keto acids and two diols when metabolic oxidation of the alkyl groups of di-ra-octylphthalate was simulated abiotically (Brodsky et al. 1986). Therefore, the in vivo and in vitro data indicate that major oxidation may occur in the remaining alkyl chain after di-ra-octylphthalate has been hydrolyzed to the... 

A further eight steps were required to convert the cyclopentanone 52 into the sulfone 59 that was deprotonated and treated with an allylic bromide (60) to afford the alkylated sulfone 61 (Scheme 7). The sulfone moiety and the benzyl ether protecting group were reductively removed in a one-pot procedure to afford a mono-protected diol (62). 

Carbamates have been prepared by heating ethyl carbamate with a higherboiling alcohol in the presence or absence of catalysts [31-33], Aluminum iso-propoxide has been reported [34] to be an excellent catalyst for the interchange reaction between ethyl carbamate and benzyl alcohol. The interchange reaction is also effective for /V-alkyl carbamates as well as unsubstituted carbamates [35]. This catalyst is effective in preparing mono- and dicarbamates in excellent yields from primary and secondary alcohols and diols. Other effective catalysts are dibutyltin dilaurate [36], dibutyltin oxide [37], sulfuric acid or p-toluenesulfonic acid [31], and sodium metal (reacts with alcohols to give the alkoxide catalyst) [33]. 

A different approach for the synthesis of di-O-methylisosorbide and other lower di-0-alkylated derivatives, using chloromethane in different solvent systems, with or without the aid of additional phase-transfer catalysts, was the subject of a patent application.181 In addition, a one-vessel dehydration -methylation reaction starting from D-glucitol was mentioned. Mixtures of mono- and di-O-methylisosorbide resulted on alkylation of the diol with... 

Alkyl-diols or alcohols may undergo etherification reactions over a solid acid catalyst. It has been demonstrated that simple diols may etherify either with mono-or di-substitution. In Scheme 12.3, if 1,6-hexanediol is used then a high conversion is obtained for the monomethylether (>60 %) this is thought to be due to the difference in polarity between the mono- and di-ether species [53]. 

Miscellaneous Reactions. - p-Toluenesulfonaraide undergoes Mitsunobu-type reactions in the presence of alcohols and cyanomethylenetriphenyl-phos-phorane (56) to give predominantly mono-N-alkylation products. This reaction has also been applied to the synthesis of cyclic ethers from diols and cyclic amines from amino alcohols and to carbon-carbon bond formation. Examples of cyclic amine synthesis include that of (+)-a-skytanthine (57). A comparative study of the reactions of active methine compounds (58) as nucleophiles using... 

Reactive diluents are low viscosity mono- or difunctionai epoxies based on aiiphatic aicohols, diols, alkylated phenols or carboxylic acid that are used to reduce the viscosity of standard epoxy resins and react with curatives during the curing process (Figure 2.42). They tend to reduce chemicai resistance, heat resistance and hardness of the coatings. The difunctionai diluents have fewer negative effects than monofunctional diluents. Higher vapor pressure (volatility) of some of the reactive diluents increases their toxicity, heaith risks and problems with skin irritancy. 

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