Reactions of Alkoxides

Sodium metal reacts vigorously with simple primary alcohols such as ethanol. 

In Section 10-6B, we learned to remove the hydroxyl proton from an alcohol by reduction with an active metal such as sodium or potassium. This reaction generates a sodium or potassium salt of an alkoxideion and hydrogen gas. 

The reactivity of alcohols toward sodium and potassium decreases in the order methyl 1° 2° 3°. Sodium reacts quickly with primary alcohols and some secondary alcohols. Potassium is more reactive than sodium and is commonly used with tertiary alcohols and some secondary alcohols. 

Some alcohols react sluggishly with both sodium and potassium. In these cases, a useful alternative is sodium hydride, usually in tetrahydrofuran solution. Sodium hydride reacts quickly to form the alkoxide, even with difficult compounds. 

The alkoxide ion is a strong nucleophile as well as a powerful base. Unlike the alcohol itself, the alkoxide ion reacts with primary alkyl halides and tosylates to form ethers. This general reaction, called the Williamson ether nthesis, is an S s 2 displacement. The alkyl halide (or tosylate) must be primary so that a back-side attack is not hindered. When the alkyl halide is not primary, elimination usually results. 

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Recall from Section 8 13 that the major pathway for reaction of alkoxide ions with secondary alkyl halides IS E2 not Sn2... 

The reaction of alkoxides with alcohols leads to the equiUbrium... 

Ethers can often be prepared by SN2 reaction of alkoxide ions, RO-. with alkyl halides. Suppose you wanted to prepare cyclohexyl methyl ether. Which of the two possible routes shown below would you choose Explain. 

Alkoxylation. A reaction of alkoxides with an alkyl halide to produce ethers, (ex R-O-Na + R Cl = R-O-R + NaCl). 

The first step in the addition of alkoxides to Cgg is, consistently, the formation of the alkoxy Cgg anion. The subsequent process is strongly dependent on the presence of oxygen. In the presence of oxygen, 1,3-dioxolane derivatives of Cgg are formed [110]. In the absence of oxygen the oligo alkoxy fullerenide anions can be formed [111, 112]. Reaction of alkoxides with Cgg usually results in complex mixtures. This may be why only a few reactions of Cgg with alkoxides have been described [113]. Nevertheless, defined alkoxy fullerenes can be obtained by nucleophilic substitution reactions of alkoxides with halogenofullerenes (Chapter 9) [113]. 

The dimethylaminooxazolidone derivative thozalinone (40-3) is described as an antidepressant. The synthesis of this agent again uses a cyanamide, provided in this case as a preformed reagent. Thus, reaction of alkoxide from ethyl mandelate (40-1) with A,A-dimethylcyanamide leads to the amidine (40-2) by addition to the nitrile. Internal displacement of the ester ethoxide group closes the ring to an oxazo-lidinone, forming the product (40-3) [42]. 

An even wider range of reactivity is observed for the reaction of alkoxide ions. For example, Blair et al. (1973) have reported the observations summarized in (64) in the gas phase. While reaction (64b) was reported to occur... 

It is well established that the nucleophilic reaction of alkoxides with 3-chlorobicyclo[1.1.0]butane-1-carbonitrile leads to 3,3-dialkoxycyclobutane-1-carbonitriles.31 The mechanism of this conversion is shown. 

In fact, the reaction of alkoxides with alkyl halides or alkyl sulfates is an important general method for the preparation of ethers, and is known as the Williamson synthesis. Complications can occur because the increase of nucleo-philicity associated with the conversion of an alcohol to an alkoxide ion always is accompanied by an even greater increase in eliminating power by the E2 mechanism. The reaction of an alkyl halide with alkoxide then may be one of elimination rather than substitution, depending on the temperature, the structure of the halide, and the alkoxide (Section 8-8). For example, if we wish to prepare isopropyl methyl ether, better yields would be obtained if we were to... 

Reaction of alkoxides and alkyl compounds (Williamson synthesis)... 

An important class of reactions of alkoxides and aryloxides involves the substitution of an alkoxide or aryloxide by protonation and elimination of alcohol or phenol (equation 56). 

Another approach to sol-gel PZT precursors involves the reaction of alkoxide mixture with glacial acetic acid [1442, 1790], Lead acetate and titanium... 

A detailed examination of the cleavage in conformers A, B, and C follows. Interestingly these three are the only conformers generated directly from reaction of alkoxide ion on a tertiary amide, with stereoelectronic control. Cleavage of conformer A can only lead to the tertiary amide, as the ejection of the amino group cannot occur with the help of the primary electronic effect (the 0 —R bond is antiperiplanar to the C-N bond). Conformer J3... 

Ligand Effects on the Reaction of Alkoxide Ions with Organophosphorus Derivatives Containing Multiple Leaving Groups... 

Table I. Products and Competitions for Forming Intermediate in the Reaction of Alkoxide Ions with Thioate Esters of Phosphorus...

Formation of both isomers (100 and 101) from the reaction of alkoxide ions with cis-(99) and fnms-2,3-dichlorohexafluoro-2-butene (102) (Park and Cook, 1965) should result from a genuine addition-elimination since elimination-addition is impossible, and there was no isomerization of the starting olefin. MeO-, EtO- and i-PrO- ions gave 95 + 2% retained cis ether (100) from the cis isomer (99), and 70 + 2% trans ether (101) from trans-( 102). The preferred retention points to short-lived carbanions. If CF8 interactions are the larger ones, as suggested by the models, the competition theory predicts predominant inversion for (99)... 

The reaction of alkoxides with thioaldehyde S-oxides, generated from sul-finates, was carefully examined by Baudin et al. [163]. A number of products were isolated, formation of which was explained by carbophilic addition of the alkoxide anions. 

First, we recall that ethers can be prepared by substitution reactions of alkoxide anion nucleophiles with alkyl halide electrophiles—the Williamson ether synthesis. The two ways to prepare the target ether are as follows ... 

The electronegative metals usually form unstable alkoxides that tend to polymerize rapidly to form [-M(OR)2-0-] . Alkoxides are easily solubilized in alcohols. Alkoxide precursors must be kept fme of water to avoid hydrolysis. Hydrolysis is the first step in the reaction of alkoxides to form gel networks. This is difficult because alkoxide solutions easily absorb water finm the atmosphere. 

In principle, alkoxy-1,3,4-thiadiazoles should be available through reaction of alkoxides with suitable halogenothiadiazoles. However,... 

Protonolysis reactions of alkoxides and aryloxides are common one example is hydrolysis of the metal alkoxide, giving metal oxide with elimination of the alcohol. Although the aim is often to avoid such a reaction, it is of great interest in the deposition of high-purity metal oxides, which are used in areas such as optoelectronics, high f superconductors, and advanced ceramics. ... 

Elsewhere in this chapter we have used oxygen nucleophilic processes to illustrate stereoselectivity (Sections II.B and II.C), coelectrophiles (Section I.A), etc. and shall not repeat these here. The literature of oxygen nucleophile attacks on alkynes includes trends in substituent effects but the data are often qualitative and usually scattered. Numerous examples indicate that the reactions of alkoxides with C2H2 are relatively slow and that most substituents facilitate the addition (Tables 13 and 14) ... 

Alcohol decomposition does provide additional insight into the interaction of adsorbates with metal oxide surfaces. The reactions of alkoxides on titanium dioxide have been used to probe thermal and photo-reactivity of powder and single crystal samples. 

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