Ethyl acetylenedicarboxylate

Aqueous Diels-Alder reaction has also been applied at the industrial level. 2,2,5-Trisubstituted tetrahydrofurans 21 are a class of active azole antifungals. Workers at Schering-Plough [21] developed a synthetic approach based on a Diels-Alder reaction between 2-arylfurans 22 and ethyl acetylenedicarboxylate (Scheme 6.9). Under thermal conditions the reaction gave a low yield of... 

Finally, the reaction with the use of ethyl acetylenedicarboxylate instead of olefin in step 3 produced surprisingly the corresponding isoxazoline (33) (Scheme 3.32) (87). 

Imines, ethyl acetylenedicarboxylate and benzoyl chloride were combined in the presence of carbon monoxide and a palladium-tri-o-tolylphosphine catalyst system to pyrrole derivatives (3.90.). Although the carbon monoxide is formally oxidized to carbon dioxide, during the catalytic cycle it is inserted into the intermediates formed and is extruded in a retro-Diels-Alder reaction only in the concluding step of the reaction sequence.114... 

The formation of pyrrole derivatives has been reported earlier. The triazoline (392) was converted by heating at its melting point into the 4-oxazoline (393) which in turn gives the 2,5-dihydropyrrole (394) on reaction with ethyl acetylenedicarboxylate (70CR(C)(27i)9S8). 

By using methyl or ethyl acetylenedicarboxylates, suitable for the Povarov reaction but also more complex aro-... 

Cycloaddition of 4-nitrofurylmethylquinolinium bromide 88 with dimethyl acetylenedicarboxylate, nitrostyrene, ethyl 3-(5-nitro-2-furyl)-2-propenoate and l-phenyl-3-(5-nitro-2-furyl)-2-propenone afforded the corresponding furylbenzoindolizine 89 (86CCC412) (Scheme 16). 

Ethyl l//-azepine-l-carboxylate (1) fails to react with simple dienophiles such as maleic anhydride and dimethyl acetylenedicarboxylate, even at 100 C 250 however, with /V-phcnyl-maleimide a [4 + 2] cycloadduct at the C2 — C5 diene system is produced.251... 

Ethyl 177-1,3-diazepine-l -carboxylates, e.g. 1, react with dimethyl acetylenedicarboxylate to yield bicyclic adducts 2 via 1,5-diazonines."... 

Treatment of the S.yV-ylide 3 with dimethyl acetylenedicarboxylate yields (amongst other products) the stable 1,2-thiazocine derivative 4 as a colorless crystalline solid, via a [6 + 2]-cycload-dition reaction. The formation of 2-ethyl, 3,4-dimethyl 5,6,7,8-tetrachloro-2//-l,2-thiazocine-2,3,4-tricarboxylate (4) may not necessarily involve a concerted mechanism.2... 

It has been shown that, on treatment with base, 1-aminopy-ridinium iodide undergoes 1,3-dipolar addition with ethyl propiolate or dimethyl acetylenedicarboxylate thus the N-aminoheterocycles may serve as convenient starting materials for the synthesis of a variety of unusual fused heterocycles.8... 

A recent method for the synthesis of the indolizine skeleton is represented by a three-component reaction between a-bromo ketones 16, pyridine 17, and ethyl propiolate or diethyl acetylenedicarboxylate. These three reagents, under microwave irradiation and catalysis by basic alumina, afforded a good variety of 3-aroyl indolizines 18 <20030L435> (Scheme 4). 

Dihydronaphthalen-1,4-iwmes from Isoindoles The naphthalen-l,4-imine derivatives 91-99 have been obtained by addition of acetylenedicarboxylic esters to the appropriate isoindoles. 3- ss Some such adducts react further with acetylenic esters (see Sections III, G and H), so that A -ethyl- and A-n-butylisoindole give 1 2 adducts with dimethyl aoetylenedicarboxylate instead. iV-Methylisoindole appears to be exceptional in giving an oily 2 1 adduct, for which structure (100) was suggested on analogy with the 2 1 adduct obtained from l,3-diphenylbenz[c]furan and acetylenedicarboxylic acid. ... 

Diaziridines 96a and 96b react with diethyl acetylenedicarboxylate to yield oily products, presumed to be 97a and 97b. These have been characterized by hydrolyzing them to the known pyrazolinones 98a and 98b, respectively [Eq. (17)]. A similar observation has been made in the reaction of l-methyl-3,3-pentamethylenediaziridine (96b) with ethyl propiolate. The reaction of 3,3-pentamethylenediaziridine with ethyl propiolate, on the other hand, yields a simple 1 1 Michael adduct. ... 

Ethyl mercaptan reacts with DMAD to give a 1 1 adduct through a trans mode of addition. WeibulP has reported that a mixture of both fumarate and maleate is formed from cyclohexyl mercaptan with propiolic acid. A similar observation has been made in the reaction of cyclohexyl mercaptan with acetylenedicarboxylic acid. ... 

Acetylenedicarboxylic acid esters and related activated alkynes are routinely used as dipolarophiles for diazo dipoles. Recent examples include the use of diazo compounds 20 (49), 23 (51), and 24 (52) (Scheme 8.7), 25 (56) (Scheme 8.8), diazoacetaldehyde dimethylacetal (41) (which after cycloaddition and deprotection gave the corresponding pyrazole-3-carbaldehyde), ethyl 3-diazopyruvate (270), p-tolyl-trifluoromethyldiazomethane (271), bis(trifluoromethyl)diazomethane (272), and diazomethylenephosphoranes (60). 

The traditional synthesis of miinchnones involves the cyclodehydration of N-acylamino acids usually with acetic anhydride or another acid anhydride. Potts and Yao (3) were apparently the first to employ dicyclohexylcarbodiimide (DCC) to generate mesoionic heterocycles, including miinchnones. Subsequently, Anderson and Heider (4) discovered that miinchnones can be formed by the cyclodehydration of N-acylamino acids using Ai-ethyl-Ai -dimethylaminopropylcarbodiimide (EDC) or silicon tetrachloride. The advantage of EDC over DCC is that the urea byproduct is water soluble and easily removed, in contrast to dicyclohexylurea formed from DCC. Although the authors conclude that the traditional Huisgen method of acetic anhydride is still the method of choice, these two newer methods are important alternatives. Some examples from the work of Anderson and Heider are shown. The in situ generated miinchnones (not shown) were trapped either with dimethyl acetylenedicarboxylate (DMAD) or ethyl propiolate. 

The cycloaddition reactions of 368 (X = CO) with 7V-phenylmaleimide, p-benzoquinone, dimethyl acetylenedicarboxylate, and tetracyanoethylene afforded [4 + 2]-cycloadducts with endo-stereochemistry ethyl acrylate gave two isomers (probably endo and exo). l,4-Dihydro-l,4-oxidonaph-thalene (19) yielded the endo-exo isomer. The Diels-Alder reaction of 368 (X = SO2) with ethyl acrylate gave a mixture of isomers, from which the higher melting product could be isolated in pure form. ... 

The methyl esters of dicarboxylic acids88 give no dicarboxylic products only mono-carboxylic acid derivatives are formed. Dimethyl succinate, dimethyl maleate and dimethyl acetylenedicarboxylate over potassium tetrafluorocobaltate(III) at 270-350"C all give mixtures of (crude products are converted into ethyl esters) ethyl pentafluoropropanoate and ethyl... 

Better yields may be obtained from vinylpyridines and alkyl propiolates, as can be seen from the conversion of 36 to the cycl[3,2,2]-azine (lw).41 Reaction of a-(bismethylthio)methylene-2-pyridineaceto-nitrile and ethyl bromoacetate using triethylamine afforded the indolizine derivative (37). Dimethyl l-carbamoyl-2-methylthiocycl-[3,2,2]azine-3,4-dicarboxylate (Iz) was synthesized by allowing dimethyl acetylenedicarboxylate to react with indolizine derivative 38, which was obtained by decarboxylation of 37 using sulfuric acid in presence of palladium-on-charcoal as catalyst [Eq. (6)].42... 

In the reversible Wittig reaction, triphenylarsine oxide reacted with electron-deficient acetylene derivatives to form stable ylides. Thus triphenylarsine oxide reacted readily with methyl propiolate, ethyl phenylpropiolate, dimethyl acetylenedicarboxylate, and hexafluoro-2-butyne as well as dicyanoacetylene to give arsonium ylides (12). The reaction temperatures required ranged from -70°C in the case of dicyanoacetylene to 130°C in the case of ethyl phenylpropiolate (15). 

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