Alkylation of alkoxides

Allylic alkoxides react with phenylsulfanylcarbene (generated from the sulfide using potassium /ert-butoxide) to give the insertion products into C —H and C —metal bonds. The prenyl derivative is the only exception apart from the insertion products 2 and 3 (more probably, 3 is formed via alkylation of alkoxide with a-chloro sulfide), the carbene adds to the double bond to give 4. 

Ether from the alkylation of alkoxides by alkyl halides. In order for reaction to go smoothly, the alkyl halides are preferred to be primary. Secondary halides work as well sometimes, but tertiary hahdes do not work at all because E2 elimination will be the predominant reaction pathway. 

Synthesis of ethers by alkylation of alkoxides with alkyl halides or alkyl sulfates ... 

Synthesis of ethers via alkylation of alkoxides—the Williamson synthesis— is efficiently executed in the PTC conditions. Since alcohols are rather weak OH acids, the effectiveness of the cataljdic process is strongly dependent on the equilibrium 14a and lipophilicity of X anions generated in the process. For these reasons, alkyl chlorides, bromides, and sulfonates should be preferred as the alkylating agents (eqs. 21-23). 

The alkylation of alkoxides of niobium and tantalum rarely lead to total substitution. Typically the reaction is free from any complication and the products are pure up to the trisubstitution stage. 

Ether from the alkylation of alkoxides by alkyl halides. 

Higher alcohols (> C3) react comparatively slowly with sodium because of the slight solubility of the sodium alkoxide in the alcohol a large excess (say, 8 mols) is therefore employed. The mixed ether is distilled off, and the process (formation of alkoxide and its reaction with the alkyl halide) may be repeated several times. The excess of alcohol can be recovered. cj/cloAliphatic alcohols form sodio compounds with difficulty if small pieces... 

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

The imide proton N-3—H is more acidic than N-1—H and hence this position is more reactive toward electrophiles in a basic medium. Thus hydantoins can be selectively monoalkylated at N-3 by treatment with alkyl haUdes in the presence of alkoxides (2,4). The mono-A/-substituted derivatives (5) can be alkylated at N-1 under harsher conditions, involving the use of sodium hydride in dimethylform amide (35) to yield derivatives (6). Preparation of N-1 monoalkylated derivatives requires previous protection of the imide nitrogen as an aminomethyl derivative (36). Hydantoins with an increased acidity at N-1—H, such as 5-arylmethylene derivatives, can be easily monoalkylated at N-3, but dialkylation is also possible under mild conditions. 

Uses. The largest use of lithium metal is in the production of organometaUic alkyl and aryl lithium compounds by reactions of lithium dispersions with the corresponding organohaHdes. Lithium metal is also used in organic syntheses for preparations of alkoxides and organosilanes, as weU as for reductions. Other uses for the metal include fabricated lithium battery components and manufacture of lithium alloys. It is also used for production of lithium hydride and lithium nitride. 

More useful than the preceding methods is cleavage of alkoxides by acetyl chloride or bromide. One, two, three, or four alkoxyls can be replaced by chloride or bromide. Benzoyl chloride gives poor yields, however. The tri- and tetrachlorides, which are stronger Lewis acids than mono- and dichlorides, coordinate with the alkyl acetate formed and yield distillable complexes (46,55,56). 

A related class of compounds are the alkyl-magnesium alkoxides these can be prepared by reaction of MgR2 with an alcohol or ketone or by reaction of Mg metal with the appropriate alcohol and alkyl chloride in methylcyclohexane solvent, e.g. ... 

A highly modified methyl testosterone derivative also exhibits antiandrogenic activity. One synthesis of this compound Involves initial alkylation of methyl testosterone (3 ) by means of strong base and methyl iodide to afford the 4,4-dimethyl derivative Formylation with alkoxide and... 

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. 

In contrast to DEC/LiC104 solutions, where typical reaction products of carbonate solvents including alkyl carbonates, alkoxides, and Li2C03 are formed at the lithium surface, DEC/LiPF6 solutions yield LiF and Li20 only [168]. 

The reaction of alkyl sulfates with alkoxide ions is quite similar to 10-12 in mechanism and scope. Other inorganic esters can also be used. One of the most common usages of the reaction is the formation of methyl ethers of alcohols and phenols by treatment of alkoxides or aroxides with methyl sulfate. The alcohol or phenol can be methylated directly, by treatment with dimethyl sulfate and alumina in cyclohexane. Carboxylic esters sometimes give ethers when treated with alkoxides (Bal2 mechanism, p. 473) in a very similar process (see also 10-24). 

Ester enolates are somewhat less stable than ketone enolates because of the potential for elimination of alkoxide. The sodium and potassium enolates are rather unstable, but Rathke and co-workers found that the lithium enolates can be generated at -78° C.69 Alkylations of simple esters require a strong base because relatively weak bases such as alkoxides promote condensation reactions (see Section 2.3.1). The successful formation of ester enolates typically involves an amide base, usually LDA or LiHDMS, at low temperature.70 The resulting enolates can be successfully alkylated with alkyl bromides or iodides. HMPA is sometimes added to accelerate the alkylation reaction. 

An important feature of the antibiotic chloramphenicol (9) is the presence of the dichloroacetamide function. Inclusion of this amide in a simpler molecule, teclozan (15), leads to a compound with antiamebic activity. Whether this is cause and effect or fortuitous is unclear. The synthesis begins with alkylation of the alkoxide derived from ethanolamine (10) with ethyl iodide to give the aminoether (11). Reaction of a,a -dibromo-p-xylene (12) with 2-nitropropane in the presence of base leads to dialdehyde (13). The reaction probably proceeds by O-alkylation on the nitropropyl anion... 

Zinc alkoxide and aryloxide complexes have been of particular interest as enzyme models and catalysts. Tetrameric alkyl zinc alkoxides are a common structurally characterized motif.81... 

The zinc alkoxide of 2-methyl-l-(3-quinolyl)propan-l-ol was used in a catalytic amount to give ee up to 94% in the enantioselective alkylation of quinoline-3-carbaldehyde by diisopropyl-... 

Carbonyl compounds addition to, 73 659 a-alkylation of, 73 658s reduction with alumina—sodium borohydride, 76 572-573 reduction with aluminum alkoxides, 76 572... 

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