Formation of ethers

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

The reactivity of the chloromethyl group is illustrated by the reaction of 2,5-dimethyl-3,4-dichloromethylthiophene (174) with water, which gives (175) Another example of ether formation, is the formation of (176) upon normal acidic workup of the reaction product from 2-thiophenemagnesium bromide and 2-thiophenaldehyde. With... 

The rate constants kTS and kST define an equilibrium constant (ATeq) connecting the singlet and triplet carbenes. An estimate of Ktq, and hence AGSX, for BA can be obtained from the experiments described above. The time resolved spectroscopic measurements indicate that BA reacts with isopropyl alcohol with a rate constant some five times slower than the diffusion limit (Table 7). This, in conjunction with the picosecond timescale measurements, gives a value for ksr. The absence of ether formation from the sensitized irradiation, when combined with the measured rate constant for reaction of 3BA with isopropyl alcohol, gives an upper limit for k-. These values give Keq and thus AGST 2 5.2 kcal mol-1 (Table 8). 

Correlation between the rate of ether formation from ethanol and the surface concentration of ethoxide species determined by IR spectroscopy [136]. 

All the absolute values of k reported in the literature are collected in Table 1. In all cases the figures should refer to the reaction of the ion-pair with monomer. The results are too fragmentary and in some cases of uncertain accuracy for a detailed discussion of the effect of environment on reactivity. A few points are clear. The reactivity of the relatively unsolvated ion-pair in hydrocarbon solvents is relatively large and may even be comparable with that of the solvated ion-pair in tetrahydrofuran despite the large difference in dielectric constant. The reactivity of the ether-solvated ion-pair in solvents of lower dielectric constant is lower than either. The first effect of etherate formation is to decrease the reactivity of the ion-pair which can be increased again by an increase of the dielectric constant of the solvent. 

Ether Formation. It is reported that the reduction products of certain a,j8-unsaturated ketones, for example, dibenzalacetone (XL), contained sonfe of the isopropyl ethers pf the carbinols.6 Carbinols of this type are especially susceptible to ether formation often recrystallization from an alcohol is sufficient to give the ether. However, ether formation is by no means the usual reaction with unsaturated ketones. Indeed, in most cases no ether was noted in the products. Even in the case of dibenzalacetone, the normal product, i.e., the carbinol, has been obtained in 58% yield.36 9,9-Dimethylanthrone-10 (XLI) gave 64% of a material corresponding in analysis to the isopropyl ether (XLII).17 Similar observations of ether formation with a-halogen ketones will be discussed later. There appears to be no way of predicting with any degree of certainty when ether formation is likely, but it is not a common side reaction. 

Later it was found that the decomposition of benzenediazonium salts with ethanol actually yields phenyl ethyl ether contaminated with a little benzene. This, coupled with the fact that a number of instances of ether formation had been recorded, led to the suggestion that the normal products of reaction between diazonium salts and ethanol are the ethers. 

Upon heating the tetrazonium chloride derived from benzidine with ethanol, an 80% yield of biphenyl is obtained without any evidence of ether formation. Extreme care is necessary to prevent the reaction from occurring violently.14... 

A methyl group ortho to each of the amino groups in benzidine again exerts a definite effect in favor of ether formation, for, whereas benzidine gives only biphenyl, o-tolidine yields approximately equal quantities of ether and hydrocarbon.14... 

The difference in initial slope is attributed to the different number of catalytic sites involved in the two reactions. If water is stripped from the liquid, coverage of the catalyst surface with water molecules decreases, and in consequence both reactions are running faster. However, the increase of ether formation is proportional to the square of the progress of the esterification, because of the square in the adsorption term in the ether rate expression (3). Therefore, stripping of water increases the rates, but lowers the selectivity at low conversion levels. 

Parera and his co-workers (359-362) have studied the poisoning effect of amines, pyridine, phenol, and acetic acid. A reduced rate of ether formation from methanol at the standard temperature of 230°C was observed when the poisons were present in the feed. In most cases the original activity was recovered, although rather slowly. Most probably the poisons were either displaced by alcohol and/or water or removed from the surface by chemical transformations. 

Figueras Roca and co-workers (346) have used preadsorbed TCNE to poison the basic sites specifically. The rate of ether formation from methanol and ethanol responded very sensitively to the poisoning with TCNE, so that the participation of basic sites in the bimolecular alcohol dehydration seems to be proved. 

Qualitatively similar results were obtained for reaction and desorption of normal and iso-propanol on the 011 [-faceted TiO2(001) surface. In the case of normal propanol, almost half of the molecules initially adsorbed desorbed as the parent molecule at 370 K, while half of the remaining surface species reacted to form propanol at 580 K. The ratio of propene to propionaldehyde generated at 580 K was 10 1. Desorption of isopropanol quantitatively mirrored the desorption of normal propanol in two desorption states at 365 and 512 K. Isopropanol did not generate any dehydrogenation products (e.g., acetone), and the surface did not generate any bimolecular coupling products for any of the probe alcohol molecules. The absence of ether formation on the (Oil [-faceted surface is consistent with the need for double-coordination vacancies to facilitate that reaction, and the absence of such sites on this surface of titanium dioxide [80]. 

Hammett p values have been established for the displacement reaction leading to ether formation. In the case of ether formation from ROH and R CH2X, the p value was negative for substituent changes in R, and positive for changes in R [26]. 

In this work the organic products were not isolated, and the possibiUty of ether formation was not considered. With methyl, ethyl, isopropyl, and tert-butyl nitrates, the principal reaction was nucleophilic substitution, but the proportion of the elimination reactions increased with increasing temperature and decreased with increasing polarity of the solvent. 

Gentry and Rudham proposed a mechanism involving oxonium ions, which led to carbonium ion formation and thence to the olefin. In the case of ether formation, a reaction between two positively changed ions, i.e. one carbonium and one oxonium ion, was proposed. Jacobs et al. disagreed with their mechanism and proposed that the ether is formed by a parallel path to olefin formation via a common intermediate. Indeed, in a later study, Rudham and StockweU, using Y-zeolites suggested a mechanism, in which a single site only is involved for ether formation and differs only in small detail from that of Jacobs et al. 

The initial rates of ether formation in the case of a 1 1 mixture of 21 and 27 and the self-reaction of 21 are approximately the same. As more 21 is added, the effect of dilution becomes apparent and the rate of ether formation falls. 

In the experiments using El-dj- and 3,3-d2-allyl alcohol in the presence and absence of pyridine bases, the results (Table IV) show that reaction occurs on Bronsted acid sites (Scheme 8), which results in diallyl ether formation with scrambling of the deuterium label via carbonium ion formation, and also on oxidizing sites on which both 1-d- and 3,3-d2-acrolein form via the formation and interconversion of the two isomeric 1,1 -d2- and 3,3-d2-allyl molybdates (27). These mechanisms are supported by data (Table IV) that show the suppression of ether formation and reduction of deuterium scrambling in the presence of base, which has little effect on the acrolein yield. The oxidation of O-allyl alcohol to acrolein over MOO3, which... 

As mentioned in Section 8.1, carbenes easily undergo insertion into O-H bonds. At an early date, Kerr et al. (1967) found that in the photolysis of diazomethane- er butanol mixtures insertion is eleven times faster at O - H than at C - H bonds. The relative rates of ether formation for methanol, ethanol, 2-propanol, and tert-butanol are 2.01 1.95 1.37 1.00. Before that investigation, Kirmse (1963) postulated that diphenylcarbene is protonated to form the diphenylmethyl carbocation, which, as a strong electrophile, adds to the alcoholate anion (or to the alcohol followed by deprotonation) forming the ether (8-26 a). Bethell et al. (1969, 1971), however, favored an electrophilic attack of diphenylcarbene at the O-atom, i. e., an ylide intermediate on the basis of isotope effects (8-26 b). Finally, a concerted process via the transition state 8.39 may be feasible (8-26 c). 

The reversibility of ether formation has been demonstrated , but it is not known whether the ether is formed from the collision of gaseous and absorbed alcohol or from adsorbed alcohol molecules only. On alumina, ethyl alcohol... 

Scheme 8.3 Synthetic application of ether formation using Meerwein s salt... 

The mechanism of 0-H bond insertion by carbenes remains an intense held of investigation. In the case of ether formation, three distinct pathways can be proposed (i) abstraction of protons from the alcohol forming an intermediate ion pair, (ii) reaction with the oxygen atom of an alcohol forming an intermediate ylide, and (hi) direct (concerted) insertion into the O-H bond. In that context, the carbene - alcohol ylide resulting from the reaction between carboethoxycarbene and MeOD has been experimentally detected for the first time, thus corroborating the viability of the ylide pathway. ... 

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