Sodium ethoxide elimination reactions

Reaction of (58) with unsaturated nittile (59) produces 5-cyanopyrazoline (60), which on treatment with sodium ethoxide eliminates hydrogen cyanide to provide the pyrazole (61) in high yield (eq. 13). 

In contrast, the regioselectivity of the reaction with acetoacetaldehyde dimethylacetal under the same conditions is poor, resulting in 67% 5-methyl-TP (89JHC1393). In the presence of sodium ethoxide, the reaction leads to 5-methyl-TP exclusively. Here, in the present authors opinion, the regioselection may be controlled by the reaction of the AT anion with the product of base-induced methanol elimination from the keto acetal. 

This Reaction should be carefully distinguished from the Claisen Conden-tation, which is the condensation of an ester, under the influence of sodium ethoxide, with (i) another ester, (ii) a ketone, or (iii) a nitrile, with the elimination of alcohol. For details of this condensation, see Ethyl Acetoacetate, p. 264. 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Substitution can take place by the S l or the 8 2 mechanism elimination by El or E2 How can we predict whether substitution or elimination will be the principal reac tion observed with a particular combination of reactants The two most important fac tors are the structure of the alkyl halide and the basicity of the anion It is useful to approach the question from the premise that the characteristic reaction of alkyl halides with Lewis bases is elimination and that substitution predominates only under certain special circumstances In a typical reaction a typical secondary alkyl halide such as iso propyl bromide reacts with a typical Lewis base such as sodium ethoxide mainly by elimination... 

The alternative combination cyclopentyl bromide and sodium ethoxide is not appropriate because elimination will be the major reaction... 

If the substituent at the 3-position is a group that can be eliminated as an anion (such as Cr, CN and NJ), the reaction proceeds without the cleavage of the C(3)—C(4) bond in the isoxazole ring and involves the ejection of the 3-substituent as an anion. For example, 3-cyanoisoxazole (114) reacted with sodium ethoxide at room temperature to give ethyl cyanoacetate (115) via an intermediate cyanoketene (32G436). 

It should be noted that when 3-acylisoxazoles (116) are heated with a base such as sodium ethoxide, the acyl group is eliminated to give a carboxylate salt and a /3-ketonitrile (117). The reaction probably occurs via initial attack at the carbonyl group (46G206). 

A fluormated enol ether formed by the reaction of sodium ethoxide with chlorotnfluoroethylene is much less reactive than the starting fluoroolefin To replace the second fluorine atom, it is necessary to reflux the reaction mixture. The nucleophilic substitution proceeds by the addition-elimination mechanism [30] (equation 26). 

Reaction of sulfones, such as CH3S02(CH2) C00Et (n = 2-5), with sodium ethoxide were shown to result in elimination when n = 2 and in cyclization when n = 3-5. By this method, tetrahydrothiapyran-3-one-1-dioxide 265, 2-methylsulfonylcyclopentanone 266 and 2-methylsulfonylcyclohexanone 267 were obtained347. Cyclization of co-cyanosulfone, CH3S02(CH2) C(CH3)2CN, gave 4,4-dimethyltetrahydrothiophene-3-one dioxide 268 when n = 1,2,2-dimethyl-5-methylsulfonylcyclopentanone 269 when n = 3 and 2,2-dimethyl-6-methylsulfonylcyclohexanone 270 when n = 4348. 

The states of reactants and products are often not given for organic reactions, because the reaction may take place at the surface of a catalyst or it may take place in a nonaqueous solvent, as here. The reaction is another example of an elimination reaction and is carried out in hot ethanol, with sodium ethoxide, NaCH CH,0, as the reagent. Some Cl I3CH2CH=CH2 is also formed in this reaction. 

Reaction of compound 37 with bromine in chloroform results in mono-bromination a to the sulfur. Treatment of this brominated derivative with NaBH3CN in AcOH gives a mixture of products resulting from reduction of the C=N double bond and of elimination of HBr. Reaction of 44 with sodium ethoxide results in the ethoxy-substituted derivative 45, whereas reaction with pyridine gives the dehydrobrominated derivative 46. Reaction of either 44 or 46 with sodium cyanide in dimethyl sulfoxide (DMSO) gives the cyano-derivative 47 <1983HCA971> (Scheme 13). 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

The final product of the reaction, the sodium derivative of ethyl acetoacetate, is then formed by elimination of sodium ethoxide and salt formation with the ethyl acetoacetate, rearranged in the enol-form ... 

Saunders and co-workers (Amin et al., 1990) used E2 elimination reactions in the p-substituted 2-phenylethyl system to test the new criteria for tunnelling suggested by the above calculations. The actual substrates and base/solvent systems they used were (2-phenylethyl-2-f)-trimethylammonium bromide, [19], with sodium ethoxide in ethanol, 2-phenylethyl-2-f bromide, [20], with potassium t-butoxide in t-butyl alcohol and 2-(p-chlorophenyl)ethyl-2-f tosylate, [21], with potassium t-butoxide in t-butyl alcohol. When equation (57) was applied to the experimental secondary (kB/ S) KIEs in Table 39, the calculated /th h KIEs were 1.106 0.033 and 1.092 0.026 for [19] and [21],... 

Williamson ether synthesis preparation of ether The sodium or potassium alkoxides are strong bases and nucleophiles. Alkoxides (RO ) can react with primary alkyl halides to produce symmetrical or unsymmetrical ethers. This is known as Williamson ether synthesis. The reaction is limited to primary alkyl halides. Higher alkyl halides tend to react via elimination. For example, sodium ethoxide reacts with ethyl iodide to produce diethyl... 

Ethyl -hydroxy benzoates.1 The dianions (LDA) of 1,3-diketones react with 1 to give ethyl 5,7-diketo-3-octenoates in 40-55% yield by an addition-elimination process. The products on reaction with dilute sodium ethoxide undergo dehydro-cyclization to afford ethyl p-hydroxybenzoates in 60-80% yield. 

The conditions used for substitution reactions by the SN2 mechanism very often lead to elimination. The reaction of 2-bromopropane with sodium ethoxide in ethanol provides a good example ... 

Cristol and co-workers (4) found that cis-p-nitrostyryl bromide 22, in the presence of ethanolic sodium ethoxide, undergoes elimination (yielding Jl ) 2300 times faster than the trans-isomer 12 which undergoes an alternative reaction of addition (- 13). 

The following Wlliamson ether synthesis is preferred. The alternate Wlliamson ether synthesis (the reaction between sodium ethoxide and tert-butyl iodide) would fail because dehydrohalogenation (that is, E2 elimination) would be faster than substitution. 

What product would be expected from the elimination reaction of (l/ ,25j-l-bromo-1,2-diphenylpropane using sodium ethoxide in ethanol as the solvent ... 

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