Alkoxide ion

Clalsen aldol condensation. This consists in the condensation of an aromatic aldehyde and an ester R—CHjCOOCjHj in the presence of finely divided sodium and a trace of alcohol at a low temperature. The catalyst is the alkoxide ion aqueous alkalis caimot be employed since they will hydrolyse the resulting ester. The product is an ap-unsaturated ester, for example ... 

Owing to the instability of a-halogenoaldehydes it is occasionally preferable to use more stable derivatives, such as enol acetate prepared according to Bedoukian s method (204) and a-bromoacetals (4, 8, 10, 16, 22, 67, 101, 426). An advantage is said to be in the yield however, this appears to be slight. The derivatives react in the same sense as the aldehydes themselves, that is, the acetal group as the more polarized reacts first and enters the C-4 position. It is likely that the condensation and cyclization occur by direct displacement of alkoxide ions. Ethyl-a,/3-dihalogeno ethers (159, 164, 177, 248) have also been used in place of the free aldehydes in condensation with thioamides. 

Alkoxide ion (RO ) The oxygen atom of a metal alkoxide acts as a nucleophile to replace the halogen of an alkyl halide The product is an ether... 

As long as the nucleophilic atom is the same the more basic the nucleophile the more reactive it is An alkoxide ion (RO ) is more basic and more nucleophilic than a carboxylate ion (RC02 )... 

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

Alkanethiolate ions (RS ) are weaker bases than alkoxide ions (RO ) and undergo synthetically useful 8 2 reactions even with secondary alkyl halides... 

The Williamson ether synthesis (Sec tion 16 6) An alkoxide ion displaces a halide or similar leaving group in an Sn2 reaction The alkyl halide cannot be one that is prone to elimination and so this reaction is limited to methyl and primary alkyl halides There is no limitation on the alkoxide ion that can be used... 

IS a two step process m which the first step is rate determining In step 1 the nucleophilic hydroxide ion attacks the carbonyl group forming a bond to carbon An alkoxide ion is the product of step 1 This alkoxide ion abstracts a proton from water m step 2 yielding the gemmal diol The second step like all other proton transfers between oxygen that we have seen is fast... 

Alkoxide ion Water intermediate Gemmal diol Hydroxide... 

Step 2 The alkoxide ion formed m the first step abstracts a proton from hydrogen... 

Aldehyde Enolate Alkoxide ion from nucleophilic addition... 

Step 2 The alkoxide ion abstracts a proton from water to give the product of aldol addition a (3 hydroxy aldehyde ... 

Water Alkoxide ion ft om nucleophilic addition Hydroxide ion Aldol... 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elim mation mechanism of nucleophilic aromatic substitution (Section 23 6)... 

Alkoxide ion (Section 5 14) Conjugate base of an alcohol a species of the type R—O... 

Weak acid (Section 1 16) An acid that is weaker than 1130" Weak base (Section 1 16) A base that is weaker than HO Williamson ether synthesis (Section 16 6) Method for the preparation of ethers involving an Sfj2 reaction between an alkoxide ion and a primary alkyl halide... 

The macrocychc hexaimine stmcture of Figure 19a forms a homodinuclear cryptate with Cu(I) (122), whereas crown ether boron receptors (Fig. 19b) have been appHed for the simultaneous and selective recognition of complementary cation—anion species such as potassium and fluoride (123) or ammonium and alkoxide ions (124) to yield a heterodinuclear complex (120). 

Silane reacts with methanol at room temperature to produce methoxymonosilanes such as Si(OCH2)4 [78-10-4] HSi(OCH2)3, and H2Si(OCH3)2 [5314-52-3] but not H SiOCH [2171 -96-2] (23). The reaction is catalyzed by copper metal. In the presence of alkoxide ions, SiH reacts with various alcohols, except CH OH, to produce tetraalkoxysHanes and hydrogen (24). 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

Solvent for Base-Catalyzed Reactions. The abihty of hydroxide or alkoxide ions to remove protons is enhanced by DMSO instead of water or alcohols (91). The equiUbrium change is also accompanied by a rate increase of 10 or more (92). Thus, reactions in which proton removal is rate-determining are favorably accompHshed in DMSO. These include olefin isomerizations, elimination reactions to produce olefins, racemizations, and H—D exchange reactions. 

Some pseudo bases are stable. 1,3-Dithiolylium adds alkoxide ions at the 2-position to give stable adducts which regenerate the starting salts with acids (80AHC(27)151). Pseudo bases can also lose water to give an ether (e.g. 167 -> 168). 

Chloro-5-arylisoxazoles undergo nucleophilic displacement with alkoxide ion. Halogen atoms in the 5-position of the isoxazole nucleus are readily displaced if an activating group is present in the 4-position (63AHC(2)365). 

In basic sohition, the alkoxide ions formed by deprotonation are even more effective nucleqrhiles. In ethanol containing sodium ethoxide, 2-chloroethanol reacts about 5000 times faster than ediyl chloridelThe product is ethylene oxide, confirming the involvement of the oxygoi atom as a nucleophile. 

The acetal might undergo ionization with formation of an alkoxide ion and a carbocation. In a second step, the alkoxide would be protonated. This mechanism is extremely rare, if not impossible, because an alkoxide ion is a poor leaving group. 

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

Detailed mechanistic studies have been carried out on aminolysis of substituted aryl acetates and aryl carbonates. Aryl esters are considerably more reactive than alkyl esters because the phenoxide ions are better leaving groups than alkoxide ions. The tetrahedral intermediate formed in aminolysis can exist in several forms which differ in extent and site of protonation ... 

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

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