Ethoxide ion reactions

The requirement for a positive j8-carbon is also reflected in Table 8, which summarizes the known Hammett p values. All these are positive, with the least reactive system showing the highest response to substituent change. The p value for the diarylhaloethylene-ethoxide ion reaction is the highest, followed by that for the reaction with the more reactive p-toluenethiolate ion. In the a-arylsulphonyl-/J-chloroethylene series, the highest values are again for the slow azide reaction, but... 

The reactivity order of the a-aroyl-j3-chloroethylene-ethoxide ion reaction does not follow the Hammett equation (Kudryavtseva et al., 1963), since the activating order of p-substituents isp-Cl>H>p-Br> p-Me. The anomalous position of the p-Br derivative, which should be more reactive than the unsubstituted one, was ascribed to the operation of the + M effect of the bromine atom, which is stronger than its usual —I effect. 

Alkyl sodium and potassium compounds, R Na+ and R K4, are strong enough bases to react with ethers, such as diethyl ether (ethoxyethane), to give ethene and the ethoxide ion (reaction 4.18). This means that ethers are unsuitable solvents for the preparation of these reactive compounds. 

The equilibrium of the last step (3), which is not actually part of the condensation mechanism, is far to the right because of the greater basic strength of the ethoxide ion as compared to (IV), and this largely assists the forward reactions in (1) and (2). The reaction mixture contains the sodium derivative of the keto-ester, and the free ester is obtained upon acidification. 

Malonic ester, like acetoacetic ester (Section 111,151), when treated with an equivalent of sodium ethoxide, forms a mono-sodium derivative, which is of great value in synthetical work. The simplest formulation of the reaction is to r rd it as an attack of the basic ethoxide ion on a hydrogen atom in the CH, group the hydrogen atoms in the CHj group are activated by the presence of the two adjacent carbethoxyl groups ... 

Reaction of the cnrbaiilon (acetone anion) with the carbonyl carbon of ethyl acetate, accompanied by the release of an ethoxide ion, to form acetyl-acetone ... 

Proton transfers convert the ammonium ion and ethoxide ion to their stable forms under the reaction conditions... 

Isoxazoles unsubstituted in the 3-position react with hydroxide or ethoxide ions to give )3-keto nitriles (243) -> (244). This reaction involves nucleophilic attack at the 3-CH group. 1,2-Benzisoxazoles unsubstituted in the 3-position similarly readily give salicylyl nitriles (67AHC(8)277), and 5-phenyl-l,3,4-oxadiazole (245) is rapidly converted in alkaline solution into benzoylcyanamide (246) (61CI(L)292). A similar cleavage is known for 3-unsubstituted pyrazoles and indazoles the latter yield o-cyanoanilines. 

The incompleteness of the other data precludes generalization. However, a few apparent inconsistencies may be indicated to stimulate further research. Insertion of another aza group into 2-chloroquinoline causes the reactivity sequence o >m (reaction with piperidine) or, even, o reaction with CgHsO"), involving only relatively small factors and, in any case, in sharp contrast with the above-mentioned effects on 2-chloropyridine as a substrate. Further, meta-aza activation in all cases involving the ethoxide ion is fairly strong suggest-... 

Relative reactivity wiU vary with the temperature chosen for comparison unless the temperature coefficients are identical. For example, the rate ratio of ethoxy-dechlorination of 4-chloro- vs. 2-chloro-pyridine is 2.9 at the experimental temperature (120°) but is 40 at the reference temperature (20°) used for comparing the calculated values. The ratio of the rate of reaction of 2-chloro-pyridine with ethoxide ion to that of its reaction with 2-chloronitro-benzene is 35 at 90° and 90 at 20°. The activation energy determines the temperature coefficient which is the slope of the line relating the reaction rate and teniperature. Comparisons of reactivity will of course vary with temperature if the activation energies are different and the lines are not parallel. The increase in the reaction rate with temperature will be greater the higher the activation energy. 

The effect of the leaving group is illustrated in the comparison of fluoro- and chloro-nitrobenzenes (Table VIII) in their reactions with ethoxide ion (lines 5 and 8) and with piperidine (lines 7 and 9). Rate ratios F Cl are 23 1 (opposing and entropy of activation changes) and 201 1 (E effect), respectively, for the two nucleophiles. For the reasons discussed in Section II, D, 1, a fluorine substituent produces a lower energy of repulsion of the nucleophile and thus facilitates reaction. 

As already mentioned, there is a striking difference in the reactivity of 1- and 3-chloroisoquinoline the former reacts about 10 times faster than the latter with both piperidine and ethoxide ion at room temperature. The lower rate of ethoxy-dechlorination of the 3-isomer is due to an E which is 10 kcal higher. It is not justified to conclude that this isomer is virtually unactivated when its rate of ethoxylation is 100,000 times that of 2-chloronaphthalene and the E for this reaction is markedly decreased (by 7 kcal) relative to that of 2-chloronaphthalene. A direct comparison of reactivity with piperidine has not been made, but a rate ratio of 500 1 can be estimated by using a factor of one-fortieth (Table X, lines 1 and 4) to make the... 

Kinetic studies have been carried out on the displacement reactions of various chloroazanaphthalenes with ethoxide ions and piperi-dine. - 2-Chloroquinoxaline is even more reactive than 2-chloro-quinazoline, thus demonstrating the powerfully electrophilic nature of the -carbon atoms in the quinoxaline nucleus. The ease of displacement of a-chlorine in the quinoxaline series is of preparative value thus, 2-alkoxy-, 2-amino-, - 2-raethylamino-, 2-dimethyl-amino-,2-benzylamino-, 2-mercapto-quinoxalines are all readily prepared from 2-chloroquinoxaline. The anions derived from substituted acetonitriles have also been used to displace chloride ion from 2-chloroquinoxaline, ... 

This four-atom replacement was observed in some reactions of uracil derivatives, containing at position 5 a substituent with the CCCN moiety. Treatment of the Z-isomer 5-(2-carbamoylvinyl)-l,3-dialkyluracil with ethanolic sodium ethoxide gave in good yield 3-ethoxycarbonylpyridin-6(lf/)-one (84%) together with 3-A-methylcarbamoyl)pyridin-6-(l7 )-one (10%) (85JOC1513) (Scheme 26). The reaction involves an initial attack of the terminal amino group of the side-chain on position 6 of the uracil molecule. C-6-N-1 bond fission and N-C bond formation yield the pyridin-6(l//)-one. A subsequent attack of the ethoxide ion on the carbonyl groups of the side-chain yields both pyridin-2-one derivatives (Scheme 26). Similar results were obtained with the -isomer. 

The elimination of HC1 from the isomeric menthyl and neomenthyl chlorides shown in Figure 11.20 gives a good illustration of this trans-diaxial requirement. Neomenthyl chloride undergoes elimination of HC1 on reaction with ethoxide ion 200 times as fast as menthyl chloride. Furthermore, neomenthyl chloride yields 3-menthene as the major alkene product, whereas menthyl chloride yields 2-nienthene. 

Base-catalyzed epoxide opening is a typical S -2 reaction in which attack of the nucleophile takes place at the less hindered epoxide carbon. For example, 1,2-epoxypropane reacts with ethoxide ion exclusively at the less highly substituted, primary, carbon to give l-ethoxy-2-propanol. 

But ethoxide ion is a strong enough base to deprotonate ethyl acetoacetate, shifting the equilibrium anrl driving the overall reaction to completion. 

Ethyl dimethylacetoacetate reacts instantly at room temperature when treated with ethoxide ion to y- ield two products, ethyl acetate and ethyl 2-methylpropanoate. Propose a mechanism for this cleavage reaction. 

Broxton and Bunnett (1979) determined the products of the reaction of 4-chloro-3-nitrobenzenediazonium ions with ethoxide ion in ethanol, which is exactly analogous to the reaction in methanol discussed earlier in this section. These authors found 12.8% 4-chloro-3-nitrophenetole, 83% 2-chloronitrobenzene, and 0.8% 2-nitrophenetole. When the reaction was carried out in C2H5OD, the first- and second-mentioned products contained 99% D and 69% D respectively. Dediazoniation in basic ethanol therefore results in a higher yield of hydro-de-diazoniation with this diazonium salt compared with the reaction in methanol. This is probably due to the slightly higher basicity of the ethoxide ion and to the more facile formation of the radical CH3-CHOH (Packer and Richardson, 1975). Broxton and McLeish (1983 c) measured the rates of (Z) — (E) interconversion for some substituted 2-chlorophenylazo ethyl ethers in ethanol. 

We shall now examine some applications of these ideas. Experiments were carried out on the reaction between isopropyl bromide and ethoxide ions. This process consists of competing elimination and nucleophilic substitution reactions,19... 

The steps are the same as in the addition-elimination mechanism, but in reverse order. Evidence for this sequence is as follows (1) The reaction does not proceed without ethoxide ion, and the rate is dependent on the concentration of this ion and not on that of ArS. (2) Under the same reaction conditions, chloroacetylene gave 83 and 80. (3) Compound 83, treated with ArS, gave no reaction but, when EtO was added, 80 was obtained. It is interesting that the elimination-addition mechanism has even been shown to occur in five- and six-membered cyclic systems, where triple bonds are greatly strained. Note that both the addition-elimination and elimination-addition sequences, as shown above, lead to overall retention of configuration, since in each case both addition and elimination are anti. 

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