Ethers reaction with alcohols

Schechter, L. Wynstra, J. Kurkjy, R. (1956). Glycidyl Ether Reactions with Alcohols, Phenols, Carboxylic Acids, and Acid Anhydrides. Journal of Industrial and Engineering Chemistry, Vol.48, No.l, (January 1956), pp. 86-93, ISSN 1226-086X. 

Schechter, L., and Wynstra, J., Glycidyl ether reactions with alcohols, phenols, carboxylic acids, and anhydrides, Ind. Eng. Chem., 48, 186, 1956. 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

Diazomethane is a yellow gas that is toxic and explosive but that may be handled safely in solution in ether. It reacts immediately with an acid to liberate nitrogen and form the methyl ester. Its reaction with alcohols to form methyl esters requires catalysis by a Lewis acid. The procedures illustrate the use of this reagent as a methylating agent (see Chapter 17, Section III, for preparation of diazomethane). 

Aldehydes and ketones undergo acid-catalyzed reaction with alcohols to yield heniiacetals, compounds that have one alcohol-like oxygen and one ether-like oxygen bonded to the same carbon. Further reaction of a hemiacetal with alcohol then yields an iicetal, a compound that has two ether-like oxygens bonded to the same carbon. 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

As seen in the retro-synthetic Scheme 5.3, intermediate 15 is useful for both routes. The choice of benzyl protection group was made based on the robust stability of benzyl phenol ethers toward most reactions and several possible avenues to remove it, although it was reported from Medicinal Chemistry that benzyl group removal via hydrogenolysis posed challenges in this compound. The choice of iodide substitution was born out of the known high reactivity of iodides in the Ullmann-type coupling reaction with alcohols and the robust stability of aryl iodides in many other common reactions. 

Whichever mechanism operates, it appears to be generally true that singlet aromatic carbenes react with the lower alcohols to form ethers at rates approaching the diffusion limit. On the other hand, aromatic carbenes that are clearly triplets do not give any ether at all from reaction with alcohols. Instead, these triplets behave as is expected of biradicals and abstract a hydrogen atom from the oxygen bearing carbon of the alcohol. The stable products of this reaction are those due to the combination and disproportionation (10) of the pair of radicals (Lapin et al., 1984). The more com-... 

Strategies for preparing mixed, acyclic acetals on insoluble supports include the oxidative haloalkoxylation of support-bound enol ethers (Entry 6, Table 6.1) and the acid-catalyzed reaction of alcohols with resin-bound enol ethers [627]. Alternatively, resin-bound a-chloro ethers can be converted to mixed acetals by reaction with alcohols or phenols in the presence of strong bases (KO/Bu, HOfBu, DMF, 5 h) [550,628]. Polystyrene-bound a-(phenylseleno)ethers react with aliphatic alcohols under slightly acidic conditions (NIS, TfOH, DCM/dioxane (1 1), 0°C to 20 °C, 1 h) to yield mixed, acyclic acetals [628],... 

Vinyl ethers undergo all of the expected reactions of olefinic compounds plus a number of other reactions. For example, vinyl ethers react with alcohols give acetals. The acetals are stable under neutral or alkaline conditions and are easily hydrolyzed with dilute acid after other desired reactions have occurred. Reaction of a vinyl ether with water gives acetaldehyde and the corresponding alcohol and reaction of vinyl ethers with carboxylic acids gives 1-alkoxyethyl esters and with thiols gives thioacetals. 

REACTIONS WITH ALCOHOLS AND CARBONYL COMPOUNDS 5.2.1 Alcohols and silyl ethers... 

The ease with which the dithiocarbamate intermediates can be prepared prompted further study of their utilization in preparing potential antioxidants by reaction with other nucleophiles. In addition to their reaction with alcohols to produce 3,5-dialkyl-4-hydroxybenzyl alkyl ethers (22) we found that the intermediates react with secondary amines to give 3,5-dialkyl-4-hydroxybenzylamines, XIV, and with primary amines to give bis (3,5-dialky 1-4-hydroxybenzy 1) amines, XV, (19). 

Alkynylbenzaldehydes yield isochromenes in a Pd-catalysed reaction with alcohols. The Pd plays a dual role, behaving as a Lewis acid to effect the formation of a hemiacetal and coordinating to the alkyne moiety to promote cyclic ether formation <02JA764>. 

A similar reaction occurs when enol ethers react with alcohols in acid solution and in the absence of water, but now we are starting in the middle of the acetal hydrolysis mechanism and going the other way, in the direction of the acetal A useful example is the formation of THP (= TetraHydroPyranyl) derivatives of alcohols from the enol ether dihydropyran. You will see THP derivatives of alcohols being used as protecting groups in Chapter 24. 

According to Baker and Gaunt, in the uncatalyzed reaction in benzene the difficult step is the formation of the intermediate polar alcohol-isocyanate complex, but once this is formed the whole reaction has a very great tendency to run downhill by a reaction with the second molecule of alcohol to give the uncharged product. On the other hand, in butyl ether there are two possibilities namely, the dissociation of the intermediate complex into isocyanate and alcohol or its further reaction with alcohol to give the urethane. These possibilities appear to be more evenly balanced in the benzene solution. 

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