Ethyl orthoacetate

A mixture of 24.7 g. (0.20 mole) of ethyl iminoacetate hydrochloride (p. 146) and 138 g. of absolute ethanol (p. 142) is stirred until the salt 

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This approach has been extended by Tieckelmann, Mulvey, and Gottis to 2-amino-5-cyanonicotinamides (16 and 18), whiob were prepared directly by partial hydrolysis of the corresponding dir itriles. Diethyl carbonate, ethyl orthoacetate, and ethyl orthoformate all underwent reaction to yield the corresponding pyrido[2,3-( ]pyri-midines (17 and 19). 

The low structural specificity in the local anesthetic sell cs is perhaps best illustrated by phenacalne (91), a local an-I -.lhetic that lacks not only the traditional ester or amide func-I ion but the basic aliphatic nitrogen as well. First prepared at I lie turn of the century, a more recent synthesis starts by con-ili iusation of p-ethoxyaniline with ethyl orthoacetate to afford I he imino ether (90), Reaction of that intermediate with a sec-I liil mole of the aniline results in a net displacement of ethanol, iiobably by an addition-elimination scheme. There is thus ob-I.lined the amidine, 91, phenacalne. 

Materials Benzyl chloride 2,44Dlchloronitrobenzone Ammonia Ethyl orthoacetate Acetic anhydride Thiourea Chlorine Iron Orthoanilamide ... 

Heat a mixture of 6 grams of 2-sulfamyl-4-chloroaniline and 15 ml of ethyl orthoacetate at 100°-110°C for 1.5 hours. Cool and filter the solids. Recrystallize from aqueous ethanol yielding 3-methyl-7-chloro-1,2,4-ben2othiadiazine-1,1-dioxide. This substance is a white crystalline solid melting at 330°C. 

Ethyloestradiol-3-ethyl ether Ethylestrenol Ethyl orthoacetate lazoxide Ethyl orthoformate Formocortal acetate Norethindrone Oxendolone Ethyl oxalate... 

In equation 8.2-6a, the slope of -1 with respect to pH refers to specific hydrogen-ion catalysis (type B, below) and the slope of + 1 refers to specific hydroxyl-ion catalysis (Q if k0 predominates, the slope is 0 (A). Various possible cases are represented schematically in Figure 8.5 (after Wilkinson, 1980, p. 151). In case (a), all three types are evident B at low pH, A at intermediate pH, and C at high pH an example is the mutarotation of glucose. Cases (b), (c), and (d) have corresponding interpretations involving two types in each case examples are, respectively, the hydrolysis of ethyl orthoacetate, of P -lactones, and of y-lactones. Cases (e) and (f) involve only one type each examples are, respectively, the depolymerization of diacetone alcohol, and the inversion of various sugars. 

Fusion of an additional heterocyclic ring onto a benzodiazepine is well known to considerably increase potency. This increase in potency is apparently maintained when the benzene ring is replaced by thiophene. Thiophene aminoketone 161 is converted to the benzodiazepine analogue 164 via chloroacetamide 162 and then glycine derivative 163 by the same sequence as that used in the benzene series. Treatment of the product 164 with phosphorus pentasulfide gives the thio-amide 165 reaction of that intermediate with hydrazine leads to the amino amidine 166. Condensation of this with ethyl orthoacetate gives the anxiolytic agent brotizolam (167) [31]. 

Triazines 347 were obtained from amidoximes 346 and ethyl orthoacetate (equation 151). The mechanism of formation of products 347 includes Beckmann rearrangement of amidoximes to carbodiimides, followed by reaction with amidoxime and orthoester. ... 

To a stirred mixture of 20.8 gm (0.25 mole) of pyridine and 40.5 gm (0.25 mole) of ethyl orthoacetate is added dropwise 40 gm (0.25 mole) of bromine over a period of hr while the temperature is kept at 10°C. The pale yellow brominated ester is filtered, the pyridine hydrobromide washed with ether, the ether washings combined with the bromo ester and then distilled to afford 44 gm (74 %), b.p. 77°-79°C (9 mm), ng 1.4393, d 1.2639. A small amount of ethyl orthodibromoacetate, b.p. 102°-104°C (8 mm), 1.469, d 1.5272, is also isolated. 

Using 2 moles of bromine and 2 moles of pyridine per mole of ethyl orthoacetate, 53 % of ethyl orthodibromoacetate can be isolated [123a]. 

Ethyl orthoacetate, 48 Ethyl orthobenzoate, 54 Ethyl orthobromoacetate, 60 Ethyl orthodibromoacetate, 60 Ethyl orthoformate, 50 Ethyl orthothioformate, 50 Ethyl a-phenylazo-a-methylacetoacetate, 299... 

Alcohols with electronegative substituents in the a-position (phenol [42] and hydroxyacetonitrile [43]) undergo only partial alcoholysis with ethyl orthoformate. The use of ethyl orthoacetate also allows only partial transesterification to take place [42, 44]. 

It seems much more likely that the transfer of the proton is actually involved in the rate-limiting step for the hydrolysis of carboxylic orthoesters. This is consistent with the observed catalytic constants. If Bunton and Dewolfe s estimate of Ka = 107 is accepted for the dissociation constant of the conjugate acid of an orthoester, and if the rate coefficient for the loss of the proton, k2, is of the order of 10" sec-1, then k, will be about 104 l mole-l sec-1, close to the value observed, for example, for the catalytic coefficient for the acid-catalyzed hydrolysis of ethyl orthoacetate at 20°C103. 

Benzyl chloride Ammonia Acetic anhydride Chlorine Orthoanilamide 2,4-Dichloronitrobenzene Ethyl orthoacetate Thiourea Iron ... 

Johnson et al. used their newly developed orthoester Claisen reaction to achieve a highly stereoselective total synthesis of aM-trans squalene (5)1 (Scheme 1.20. The diene diol 6 underwent Johnson-Claisen rearrangement when it was heated with ethyl orthoacetate in the presence of propionic acid for 3 h at 138 C. The diene dialdehyde 7, obtained by treatment of the resulting ester with lithium aluminum hydride followed by oxidation with Collins reagent, reacted with 2-propenyllithium to give the tetraene diol 8. The tetraene dialdehyde 9, which... 

A third possibility of a mechanism leading to general acid catalysis is the equilibrium formation of a hydrogen-bonded addition compound of substrate and general acid, followed by slow decomposition of the addition complex to the products [27], Such a mechanism is not very likely for reactions in aqueous solutions. However, it has been suggested for the general acid catalyzed hydrolyses of ethyl orthoformate and ethyl orthoacetate in 60 % aqueous dioxane [28]. 

The hydrolysis reactions of acetals, ketals, and orthoesters are catalyzed by acids but not by bases. It has been found that these three groups of substrates are hydrolyzed via a common general mechanism — involving similar types of intermediates — though the rate-determining step may vary from case to case. In the hydrolyses of ethyl orthoacetate, orthopropionate, and orthocarbonate, general acid catalysis was unambiguously established for the first time by Bronsted and Wynne-Jones [158]. 

The hydrolyses of ethyl orthoacetate, ethyl ortho propionate, and ethyl orthocarbonate in aqueous solutions undergo general catalysis by acids [158]. On the other hand, general acid catalysis appears to be absent in the hydrolyses of orthoformates and orthobenzoates if the reactions are carried out in water or in 20 % dioxane—water [158, 28], General acid catalysis can be observed in the hydrolyses of these substrates in solvents with higher percentages of dioxane [28] or in 70 % methanol—water [169],... 

The hydrolyses of ethyl orthoacetate, ethyl orthopropionate, and ethyl orthocarbonate must occur with rate-determining proton transfer (A-SE2) even in purely aqueous solution. A solvent isotope effect of kH/kD = 0.7 has been found for ethyl orthocarbonate [159, 184]. 

Ortho esters may be brominated in pyridine solution. The reaction takes place rapidly at 10-30° to give good yields of a-bromoortho esters. Higher yields are obtained when a mixture of carbon tetrachloride and pyridine is used as solvent. The reaction fails for ethyl orthoisobutyrate. Two a-hydrogen atoms of ethyl orthoacetate have been replaced by bromine atoms to give ethyl orthodibromoacetate (53%). ... 

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