Ethyl orthoacetate, reaction with

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. 

Wolfbeis investigated the reactions of amines and orthoesters with different CH-acid molecules (81CB3471). When the reactions of aniline, ethyl orthoformate, and dialkyl malonates (2 mol) were carried out at 130-140°C for 4 hr, phenylaminomethylenemalonamates (245) were obtained (81CB3471). Similar reactions with aliphatic amines were unsuccessful. Phenylaminomethylenemalonic acid could not be prepared in the reactions of aniline, methyl orthoformate or orthoacetate, and malonic acid. When these reactions were carried out in 2-propanol, only amidines (246) were obtained. 

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

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. ... 

Claisen rearrangement of aUylic alcohols to ethyl dienoates. Claisen rearrangement of allylic alcohols with an orthoacetate is known to provide 2-carbon homologated y,8-unsaturated esters (6, 607-608). Reaction with the phenylsulfinylorthoacetate 1 is accompanied by an in situ sulfoxide elimination to provide 2-carbon homologated dienoate esters (equation I). This novel reagent was used to convert the... 

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... 

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],... 

Reaction of amidoximes with ethyl orthoacetate and acid catalyst gave the 1,3,5-triazine-V-oxides... 

The Johnson rearrangement involves reaction of an allylic alcohol with ethyl orthoacetate to give a mixed ortho ester that loses ethanol and then undergoes... 

Leucine n-propylamide mixed with ethyl orthoacetate, a little acetic acid added, gently heated until the reaction starts, then kept 1-1.5 hrs. at 110-120 1 -n-propyl-2-methyl-4-isobutyl-5 (4H) -imidazolone. Y 70%. F. e. s. S. Ginsburg, J. Org. Ghem. 27, 4062 (1962) method s. J. Brunken and G. Bach, B. 89, 1363 (1956). 

Preparation of triethyl orthoacetate by the reaction of ethyl 1,1-diazido-ethyl ether with sodium ethoxide [207]. 

The reaction of ribonucleosides with ethyl orthoformate or methyl orthoacetate under acid-catalyzed conditions affords the 2, 3 -0-(ethoxy-methylidene) (99, R = H, R = CsHs) and the 2, 3 -0-(methoxy-ethylidene) (R = CHs, R = CHs) acetals, respectively. These acetals... 

JCS(P1)447>. Related reactions are the oxidative cyclization of 3-amino-6-chloro-l-phenyl- , 2,4-benzothiadiazine 1-oxide (108 R =Ph, R = C1) to the 52 -l,2,4-triazolo[5,l-c][l,2,4]-benzo-thiadiazine 5-oxide (109) with triethyl orthoacetate in the presence of alcoholic ammonia and lead tetraacetate <86GEP3433307>, and the ring closures of the amines (108 R = Me, Ph R = H) to 5A -imidazo[l,2-c][l,2,4]benzothiadiazine S -oxides (110 R = Me, Ph) with ethyl bromopyruvate (Scheme 12) <88JMC1098>. 

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